Vitamin C (Ascorbic Acid)

BACKGROUND: This systematic review and meta-analysis aimed to determine whether the combination of hydrocortisone, vitamin C (ascorbic acid), and thiamine (HAT therapy) diminishes the mortality and is effective in expediting the resolution of sepsis and septic shock or not. METHODS: The following databases of PubMed, Scopus, ISI Web of Science, and Google Scholar were explored until March 2021 for all existing literature related to this field. An automatic alert for all databases was also activated to update our search. Meta-analysis was performed on clinical trials and cohorts separately as well as on all the pooled populations. RESULTS: This study evaluated nine clinical trials (1358 participants) and nine cohorts (339,437 participants) and is the most comprehensive systematic review in this field. The results of our meta-analysis demonstrated a significant difference in the reduction of Sepsis-Related Organ Failure Assessment (SOFA) score changes (Δ-SOFA) over 72 h (Standard Mean Difference (SMD) = -0.429; 95% CI: -0.737, 0.120; p = 0.006), duration of vasopressor (VP) (SMD = -0.373; 95% CI: -0.619, -0.128; p = 0.003), and procalcitonin (PCT) clearance (SMD = 0.496; 95% CI: 0.061, 0.931%; p = 0.026). Considering the results of cohorts, HAT therapy was effective in the survival of intensive care units (ICUs) patients (OR = 0.641; 95% CI: 0.423-0.970, p = 0.035). However, no significant difference was observed between the intervention and control groups in hospital mortality (Odds Ratio (OR) = 0.811, 95% CI: 0.544-1.209, p = 0.304), 28- to 30-day mortality (OR = 1.000; 95% CI: 0.782-1.279, p = 0.998), new onset acute kidney injury requiring renal replacement therapy ((OR = 0.856, 95% CI: 0.526, 1.391; p = 0.529), in-hospital length of stay (LOS) (SMD = 0.090; 95% CI: -0.036, 0.216 days; p = 0.162), LOS in ICU (SMD = 0.016, 95% CI: -0.138, 0.170 days; p = 0.838), and mechanical ventilation-free days (SMD = 0.004; 95% CI: -0.154, 0.163 days; p = 0.956). CONCLUSION: Supplementation of septic and septic shock patients with HAT therapy has significant beneficial effects on SOFA score over 72 hours, duration of exogenous vasopressor infusion and procalcitonin clearan

BACKGROUND: Vitamin C (ascorbic acid) seems to attenuate the overproduction of reactive species during and after exercises. Yet, no meta-analysis has summarized the magnitude of this effect. The objective of this study was to systematically review the effects of vitamin C supplementation on oxidative stress, inflammatory markers, damage, soreness, and the musculoskeletal functionality after a single bout of exercise. METHODS: Major electronic databases were searched, from inception to September 2019, for placebo-controlled randomized clinical trials (RCTs) that evaluated the effects of vitamin C supplementation on oxidative stress parameters, inflammation markers, muscle damage, muscle soreness, and muscle functionality after a single bout of exercise in healthy volunteers. Random-effects modelling was used to compare mean changes from pre- to postexercise in participants that were supplemented with vitamin C versus placebo. Data were reported as standard mean difference (SMD) and 95% confidence interval (CI). RESULTS: A total of 18 RCTs, accounting for 313 participants (62% males, median age = 24 years) were included. Vitamin C supplementation reduced lipid peroxidation immediately (SMD = - 0.488; 95% CI = - 0.888 to - 0.088), 1 h (SMD = - 0.521; 95% CI = - 0.911 to - 0.131) and between 1 and 2 h (SMD = - 0.449; 95% CI = - 0.772 to - 0.126) following exercise. Exercise induced interleukin-6 (IL-6) response was attenuated 2 h (SMD = - 0.764; 95% CI = - 1.279 to - 0.248) and between 1 and 2 h (SMD = - 0.447; 95% CI = - 0.828 to - 0.065) after exercise. No effects of vitamin C supplementation were found on creatine kinase (CK), C-reactive protein (CRP), cortisol levels, muscle soreness, and muscle strength. CONCLUSION: Vitamin C supplementation attenuates the oxidative stress (lipid peroxidation) and inflammatory response (IL-6) to a single bout of exercise. REGISTRATION: PROSPERO (CRD42018094222).

BACKGROUND: Vitamin C (ascorbic acid) for preventing and treating the common cold has been a subject of controversy for 70 years. OBJECTIVES: To find out whether vitamin C reduces the incidence, the duration or severity of the common cold when used either as a continuous regular supplementation every day or as a therapy at the onset of cold symptoms. SEARCH METHODS: We searched CENTRAL 2012, Issue 11, MEDLINE (1966 to November week 3, 2012), EMBASE (1990 to November 2012), CINAHL (January 2010 to November 2012), LILACS (January 2010 to November 2012) and Web of Science (January 2010 to November 2012). We also searched the U.S. National Institutes of Health trials register and WHO ICTRP on 29 November 2012. SELECTION CRITERIA: We excluded trials which used less than 0.2 g per day of vitamin C and trials without a placebo comparison. We restricted our review to placebo-controlled trials. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data. We assessed 'incidence' of colds during regular supplementation as the proportion of participants experiencing one or more colds during the study period. 'Duration' was the mean number of days of illness of cold episodes. MAIN RESULTS: Twenty-nine trial comparisons involving 11,306 participants contributed to the meta-analysis on the risk ratio (RR) of developing a cold whilst taking vitamin C regularly over the study period. In the general community trials involving 10,708 participants, the pooled RR was 0.97 (95% confidence interval (CI) 0.94 to 1.00). Five trials involving a total of 598 marathon runners, skiers and soldiers on subarctic exercises yielded a pooled RR of 0.48 (95% CI 0.35 to 0.64).Thirty-one comparisons examined the effect of regular vitamin C on common cold duration (9745 episodes). In adults the duration of colds was reduced by 8% (3% to 12%) and in children by 14% (7% to 21%). In children, 1 to 2 g/day vitamin C shortened colds by 18%. The severity of colds was also reduced by regular vitamin C administration.Seven comparisons examined the effect of therapeutic vitamin C (3249 episodes). No consistent effect of vitamin C was seen on the duration or severity of colds in the therapeu

BACKGROUND: The role of vitamin C (ascorbic acid) in the prevention and treatment of the common cold has been a subject of controversy for 60 years, but is widely sold and used as both a preventive and therapeutic agent. OBJECTIVES: To discover whether oral doses of 0.2 g or more daily of vitamin C reduces the incidence, duration or severity of the common cold when used either as continuous prophylaxis or after the onset of symptoms. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2006); MEDLINE (1966 to December 2006); and EMBASE (1990 to December 2006). SELECTION CRITERIA: Papers were excluded if a dose less than 0.2 g per day of vitamin C was used, or if there was no placebo comparison. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. 'Incidence' of colds during prophylaxis was assessed as the proportion of participants experiencing one or more colds during the study period. 'Duration' was the mean days of illness of cold episodes. MAIN RESULTS: Thirty trial comparisons involving 11,350 study participants contributed to the meta-analysis on the relative risk (RR) of developing a cold whilst taking prophylactic vitamin C. The pooled RR was 0.96 (95% confidence intervals (CI) 0.92 to 1.00). A subgroup of six trials involving a total of 642 marathon runners, skiers, and soldiers on sub-arctic exercises reported a pooled RR of 0.50 (95% CI 0.38 to 0.66). Thirty comparisons involving 9676 respiratory episodes contributed to a meta-analysis on common cold duration during prophylaxis. A consistent benefit was observed, representing a reduction in cold duration of 8% (95% CI 3% to 13%) for adults and 13.6% (95% CI 5% to 22%) for children. Seven trial comparisons involving 3294 respiratory episodes contributed to the meta-analysis of cold duration during therapy with vitamin C initiated after the onset of symptoms. No significant differences from placebo were seen. Four trial comparisons involving 2753 respiratory episodes contributed to the meta-analysis of cold severity during therapy and no significant differences from placebo were seen.

Erratum in JAMA. 2008 Feb 20;299(7):765-6. Comment in ACP J Club. 2007 Jul-Aug;147(1):4. doi: 10.7326/ACPJC-2007-147-1-004. JAMA. 2007 Jul 25;298(4):400-1; author reply 402-3. doi: 10.1001/jama.298.4.400-b. JAMA. 2007 Jul 25;298(4):400; author reply 402-3. doi: 10.1001/jama.298.4.400-a. JAMA. 2007 Jul 25;298(4):401-2; author reply 402-3. doi: 10.1001/jama.298.4.401-b. JAMA. 2007 Jul 25;298(4):401; author reply 402-3. doi: 10.1001/jama.298.4.401-a. Nutr Cancer. 2008;60(1):1-6. doi: 10.1080/01635580701806699. CONTEXT: Antioxidant supplements are used for prevention of several diseases. OBJECTIVE: To assess the effect of antioxidant supplements on mortality in randomized primary and secondary prevention trials. DATA SOURCES AND TRIAL SELECTION: We searched electronic databases and bibliographies published by October 2005. All randomized trials involving adults comparing beta carotene, vitamin A, vitamin C (ascorbic acid), vitamin E, and selenium either singly or combined vs placebo or vs no intervention were included in our analysis. Randomization, blinding, and follow-up were considered markers of bias in the included trials. The effect of antioxidant supplements on all-cause mortality was analyzed with random-effects meta-analyses and reported as relative risk (RR) with 95% confidence intervals (CIs). Meta-regression was used to assess the effect of covariates across the trials. DATA EXTRACTION: We included 68 randomized trials with 232 606 participants (385 publications). DATA SYNTHESIS: When all low- and high-bias risk trials of antioxidant supplements were pooled together there was no significant effect on mortality (RR, 1.02; 95% CI, 0.98-1.06). Multivariate meta-regression analyses showed that low-bias risk trials (RR, 1.16; 95% CI, 1.04[corrected]-1.29) and selenium (RR, 0.998; 95% CI, 0.997-0.9995) were significantly associated with mortality. In 47 low-bias trials with 180 938 participants, the antioxidant supplements significantly increased mortality (RR, 1.05; 95% CI, 1.02-1.08). In low-bias risk trials, after exclusion of selenium trials, beta carotene (RR, 1.07; 95% CI, 1.02-1.11), vitamin A (RR, 1.16; 95% CI, 1.10-1.24), and vitamin E (RR, 1.04; 95

OBJECTIVE: To evaluate the literature on supplemental vitamin C and vitamin E therapy in the prevention and treatment of Alzheimer's disease (AD). DATA SOURCES: Literature retrieval was accessed through MEDLINE (1966-March 2005) using the key words antioxidants, vitamin C, vitamin E, Alzheimer's disease, and dementia. International Pharmaceutical Abstracts (1970-March 2005), Current Contents (1996-March 2005), Cochrane Database of Systematic Reviews (1994-March 2005), and Ebsco's Academic Search Elite (1975-March 2005) were searched with the same key words. STUDY SELECTION AND DATA EXTRACTION: Articles related to the objective that were identified through PubMed were included. DATA SYNTHESIS: Oral supplementation of vitamin C (ascorbic acid) and vitamin E (D-alfa-tocopherol acetate) alone and in combination have been shown to decrease oxidative DNA damage in animal studies in vivo, in vitro, and in situ. Recent results of a prospective observational study (n = 4740) suggest that the combined use of vitamin E 400 IU daily and vitamin C 500 mg daily for at least 3 years was associated with the reduction of AD prevalence (OR 0.22; 95% CI 0.05 to 0.60) and incidence (HR 0.36; 95% CI 0.09 to 0.99). Contradicting this is a previous prospective observational study (n = 980) evaluating the relationship between 4 years of vitamin C and E intake and the incidence of AD, which detected no difference in the incidence of AD during the 4-year follow-up. Recent meta-analysis results suggest that doses of vitamin E > or =400 IU daily for more than one year are associated with increased all-cause mortality. Mega-trial results suggest that vitamin E doses > or =400 IU daily for 6.9 years in patients with preexisting vascular disease or diabetes mellitus increase the incidence of heart failure, with no other outcome benefits noted. CONCLUSIONS: In the absence of prospective, randomized, controlled clinical trials documenting benefits that outweigh recently documented morbidity and mortality risks, vitamin E supplements should not be recommended for primary or secondary prevention of AD. Although the risks of taking high doses of vitamin C are lower than those with vitamin E, the l

BACKGROUND: The role of oral vitamin C (ascorbic acid) in the prevention and treatment of the common cold has been a subject of controversy for at least sixty years. Public interest in the topic continues to be high and vitamin C continues to be widely sold and used as a preventive and therapeutic agent for this common ailment. OBJECTIVES: To discover whether oral vitamin C in doses of 200 mg or more daily, reduces the incidence, duration or severity of the common cold when used either as continuous prophylaxis or after the onset of cold symptoms. SEARCH STRATEGY: This updated review added to earlier searches, a full search of the following electronic databases: the Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2004); MEDLINE (January 1966 to June 2004); and EMBASE (1990 to June 2004). SELECTION CRITERIA: Papers were excluded if a dose less than 200 mg daily of vitamin C was used; if there was no placebo comparison; if methods of outcome assessment were inadequately described; and if the report did not record any of the three study outcomes (incidence, duration or severity) in sufficient detail to enter into the meta-analysis. Three criteria of study quality were assessed: Jadad scores, placebo distinguish-ability, and allocation concealment. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. 'Incidence' of colds during prophylaxis was assessed as the proportion of participants experiencing one or more colds during the study period. 'Duration' was the mean days of illness of cold episodes and 'severity' of these episodes was assessed by days confined indoors, off work or school. or by symptom severity scores. MAIN RESULTS: Twenty-nine trial comparisons involving 11,077 study participants contributed to the meta-analysis on the relative risk (RR) of developing a cold while taking prophylaxis. The pooled RR was 0.96 (95% CI 0.92 to 1.00). A subgroup of six trials that involved a total of 642 marathon runners, skiers, and soldiers on sub-arctic exercises reported a pooled RR of 0.50 (95%CI 0.38 to 0.66). Thirty comparisons that involved 9,676 respiratory episodes contributed to the m

BACKGROUND: Maintaining adequate hydration is critical to optimal health, well-being, and performance. Those who are physically active in stressful environments, such as warm and/or humid scenarios, may be at particular risk for dehydration with ensuing loss of electrolytes, leading to sluggishness and impaired physical performance. METHODS: We evaluated an electrolyte and amino acid product containing L-alanine and L-glutamine, as well as select vitamins [B3 (niacin), B5 (pantothenic acid), B6 (pyridoxine), B12 (cobalamin), and vitamin C (ascorbic acid)]. Subjects (n = 40; four groups, n = 10) were randomized to consume either a placebo packet or one, two, or three packets daily of the test product for 4 weeks with site visits at 0, 2, and 4 weeks. We tested safety and tolerability by analyzing hematological parameters (complete blood counts), metabolic parameters (hepatic, renal, acid-base balance), urinalysis end products, thyroid status [T3 (triiodothyronine), T4 (thyroxine), TSH (thyroid-stimulating hormone)], tolerability (via questionnaire), vital signs, and dietary intake. RESULTS: Statistical analyses displayed ten significant main effects (p < 0.05) with white blood cells, lymphocytes, neutrophils, urinary pH, thyroxine, urination frequency, calcium, calories, fat, and cholesterol. Interactions for time and group (p < 0.05) were observed for MCV, eGFR, potassium, overall tolerability, bloating, and cramping-demonstrating mild GA disturbances. Little to no change of physiological relevance was noted for any outcome variable, regardless of dosing level. CONCLUSIONS: Our results indicate the product was well-tolerated at all dosing levels and no significant adverse changes occurred in any of the test parameters compared to the placebo group, indicating relative safety of ingestion over a 4-week treatment period, at the volumes used, and outside the context of physical stress.

Vitamin C (ascorbic acid) is an important water-soluble antioxidant associated with decreased oxidative stress in type 2 diabetes (T2D) patients. A previous targeted plasma proteomic study has indicated that ascorbic acid is associated with markers of the immune system in healthy subjects. However, the association between the levels of ascorbic acid and blood biomarkers in subjects at risk of developing T2D is still unknown. Serum ascorbic acid was measured by ultra-performance liquid chromatography and serum proteins were quantified by untargeted liquid-chromatography mass spectrometry in 25 hyperinsulinemia subjects that were randomly assigned a high dairy intake diet or an adequate dairy intake diet for 6 weeks, then crossed-over after a 6-week washout period. Spearman correlation followed by gene ontology analyses were performed to identify biological pathways associated with ascorbic acid. Finally, machine learning analysis was performed to obtain a specific serum protein signature that could predict ascorbic acid levels. After adjustments for waist circumference, LDL, HDL, fasting insulin, fasting blood glucose, age, gender, and dairy intake; serum ascorbic acid correlated positively with different aspects of the immune system. Machine learning analysis indicated that a signature composed of 21 features that included 17 proteins (mainly from the immune system), age, sex, waist circumference, and LDL could predict serum ascorbic acid levels in hyperinsulinemia subjects. In conclusion, the result reveals a correlation as well as modulation between serum ascorbic acid levels and proteins that play vital roles in regulating different aspects of the immune response in individuals at risk of T2D. The development of a predictive signature for ascorbic acid will further help the assessment of ascorbic acid status in clinical settings.

OBJECTIVE: Vitamin C/Ascorbic acid inhibits tyrosinase enzyme causing melanin biosynthesis suppression. This study aimed to compare the efficacy of intra-mucosal injection (mesotherapy) with topical gel as non-surgical methods for managing gingival hyperpigmentation. MATERIALS AND METHODS: Twenty healthy non-smokers with mild to severe hyperpigmented gingiva were randomly assigned for Mesotherapy (G1); intra-mucosal injection of ascorbic acid (1/week/3 weeks); or Gel (G2), topical ascorbic acid gel (1/day/3 months). Pigmentation index (DOPI), patient satisfaction, as well as histological analysis for Fontana-Masson-stained specimens were performed at baseline and after 6 months. Comparison between groups and changes by time were analyzed using Mann-Whitney and Friedman's tests, respectively. RESULTS: The median DOPI significantly decreased after 1 month in G1 (P value < 0.001, r = 0.9) compared with non-significant change in G2. No pain experienced during or after treatment in both groups. G1 patients showed significantly higher satisfaction with treatment than G2. Mean area fraction of melanin forming cells was significantly reduced in both groups after 6 months, but the effect size was higher in G1 (r = 0.886) than in G2 (r = 0.797). CONCLUSIONS: Vitamin C mesotherapy showed better and early effect than topical gel, and both techniques were not painful and esthetically satisfying in managing gingival hyperpigmentation. CLINICAL RELEVANCE: Gingival melanin pigmentation causes esthetic concerns for significant number of patients. Investigating non-surgical depigmentation techniques to decrease postoperative complications and patient discomfort, pain and long healing period associated with surgical methods would be clinically significant. © 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Candida albicans (C. albicans) is a main cause of hospital-acquired fungal infections. Combination therapy is promising as a novel anti-C. albicans strategy because of its better efficacy. Theasaponins are pentacyclic triterpenes in the Camellia genus with multiple biological activities. Our previous studies prove that theasaponins display inhibitory activity against C. albicans. Ascorbic acid (VC) is a vitamin found in many plants that shows potential in combination therapy. However, whether VC enhances the activity of theasaponins remains unclear. In this study, the checkerboard micro-dilution method was used to assess the effect of VC (0-80 mmol/L) on the anti-C. albicans effect of theasaponins (0-1000 μg/mL). Then, the effects of theasaponins (31.25 μg/mL), VC (80 mmol/L), and theasaponins (31.25 μg/mL) + VC (80 mmol/L) on C. albicans planktonic cells and different stages of biofilm formation were assessed. Transcriptomic analysis was conducted to investigate the molecular mechanisms. According to the results, VC enhanced the anti-planktonic and anti-biofilm effect of theasaponins against C. albicans. The minimum inhibitory concentration of theasaponins was significantly decreased and the fungicidal efficiency was increased with the addition of VC. VC remarkably aggravated the suppression of theasaponins with regard to various virulence factors of C. albicans, including adhesion, early biofilm formation, mature biofilm, cell surface hydrophobicity, and phospholipase activity. Compared with the theasaponins or VC groups, the level of intracellular reactive oxygen species was higher, while the levels of mitochondrial membrane potential and adenosine triphosphate were lower in the combination group, suggesting more severe oxidative stress, mitochondrial injury, and energy deficiency. Transcriptomic analysis revealed that the combination predominantly suppressed the pathways of glycolysis, glycerophospholipid metabolism, glutathione metabolism, and cysteine and methionine metabolism. This implied that energy deficiency and redox imbalance were associated with the anti-C. albicans activity of the combination. These results prove that VC enhances the inhibitory ef

Alpha-tocopheryl succinate (αTOS), vitamin K3 (VK3) and vitamin C (ascorbic acid, AA) were previously shown to synergistically promote different death pathways in carcinoma cells, depending on their concentrations and combinations. Similar effects were observed herein in melanoma cells, although αTOS behaved as an antagonist. Interestingly, suboptimal cell death-inducing concentrations (1.5 μM αTOS/20 μM AA/0.2 μM VK3) effectively up-regulated activating Natural Killer (NK) cell ligands, including MICA (the stress-signaling ligand of the NKG2D receptor), and/or the ligands of at least one of the natural cytotoxicity receptors (NKp30, NKp44 and NKp46) in 5/6 melanoma cell lines. Only an isolated MICA down-regulation was seen. HLA class I, HLA class II, ULBP1, ULBP2, ULBP3, Nectin-2, and PVR displayed little, if any, change in expression. Ligand up-regulation resulted in improved lysis by polyclonal NK cells armed with the corresponding activating receptors. These results provide the first evidence for concerted induction of cell death by cell-autonomous and extrinsic (immune) mechanisms. Alarming the immune system much below the cell damage threshold may have evolved as a sensitive readout of neoplastic transformation and oxidative stress. Cocktails of vitamin analogues at slightly supra-physiological dosages may find application as mild complements of melanoma treatment, and in chemoprevention.

Amphotericin B (AmB) remains the antifungal polyene of choice in deep fungal infections, but its high toxicity to mammalian cells limits its use. This toxicity is partly due to lipid peroxidation exerted by amphotericin B in cell membranes. The work we have undertaken focused on the one part the evaluation of the efficacy of amphotericin B in the presence of some antioxidants vitamins (vitamin C "ascorbic acid" and vitamin E "α-tocopherol") against the yeast Candida albicans ATCC 10231. Secondly, we have tested the cytotoxicity of these formulations on human red blood cells. The results showed a significant improvement in the efficiency of our formulations tested from 7% to 12% compared with amphotericin B alone at therapeutic concentrations. Furthermore, the addition of vitamin C and vitamin E protects human red blood cells against the cytotoxicity induced by amphotericin B with 17%. This is due may be to the antioxidant power of vitamins which confer protection against the autoxidation of the molecule of amphotericin B. On the other hand, it is noticed that the yeast regrows after 24h whatever in complex with vitamin C or vitamin E of the stock solution. On completion of this study, the incorporation of antioxidant vitamins that we propose to the reaction medium of antifungal improved the therapeutic index of amphotericin B.

BACKGROUND: Both resveratrol and vitamin C (ascorbic acid) are frequently used in complementary and alternative medicine. However, little is known about the underlying mechanisms for potential health benefits of resveratrol and its interactions with ascorbic acid. METHODS: The antioxidant enzymes heme oxygenase-1 and paraoxonase-1 were analysed for their mRNA and protein levels in HUH7 liver cells treated with 10 and 25 μmol/l resveratrol in the absence and presence of 100 and 1000 μmol/l ascorbic acid. Additionally the transactivation of the transcription factor Nrf2 and paraoxonase-1 were determined by reporter gene assays. RESULTS: Here, we demonstrate that resveratrol induces the antioxidant enzymes heme oxygenase-1 and paraoxonase-1 in cultured hepatocytes. Heme oxygenase-1 induction by resveratrol was accompanied by an increase in Nrf2 transactivation. Resveratrol mediated Nrf2 transactivation as well as heme oxygenase-1 induction were partly antagonized by 1000 μmol/l ascorbic acid. CONCLUSIONS: Unlike heme oxygenase-1 (which is highly regulated by Nrf2) paraoxonase-1 (which exhibits fewer ARE/Nrf2 binding sites in its promoter) induction by resveratrol was not counteracted by ascorbic acid. Addition of resveratrol to the cell culture medium produced relatively low levels of hydrogen peroxide which may be a positive hormetic redox-signal for Nrf2 dependent gene expression thereby driving heme oxygenase-1 induction. However, high concentrations of ascorbic acid manifold increased hydrogen peroxide production in the cell culture medium which may be a stress signal thereby disrupting the Nrf2 signalling pathway.

Previous experiments in rats with chemically induced colitis have shown that the antioxidant N-acetylcysteine plus mesalamine (5-ASA) exerted a significantly greater therapeutic effect in promoting mucosal healing when compared to either agent alone. The aims of the present study were to compare the effects of three antioxidants plus mesalamine vs. 5-ASA alone in treatment of colitis induced by trinitrobenzene sulfonic acid (TNBS) in rats. METHODS: Three days following induction of TNBS colitis, rats received 8 days of rectal therapy with 5-ASA, or 5-ASA plus vitamin C (ascorbic acid), 5-ASA plus phenyl butylnitrone (PBN) and 5-ASA plus vitamin E (alpha-tocopherol). Distal colonic tissues were examined for microscopic colitis and myeloperoxidase (MPO) activity. RESULTS: Global assessments of microscopic colitis induced by TNBS indicated that 5-ASA alone significantly changed colonic injury by -31%. Combination therapy with ascorbic acid plus 5-ASA or alpha-tocopherol plus 5-ASA caused further significant change in TNBS colitis by -65 and -82%, respectively. Each of these values was significantly below scores observed with 5-ASA as monotherapy. Reduction in colitis with PBN plus 5-ASA was not different from 5-ASA alone. MPO activity was decreased significantly in response to monotherapy with 5-ASA and each of the antioxidants plus 5-ASA when compared to TNBS. alpha-Tocopherol plus 5-ASA, however, was the only treatment strategy that reduced significantly MPO activity below that recorded for 5-ASA alone. In conclusion, our results indicate that antioxidants other than N-acetylcysteine significantly enhance the therapeutic effectiveness of 5-ASA in the treatment of TNBS colitis. alpha-Tocopherol plus 5-ASA exerted profound anti-inflammatory and reparative effects upon colitis induced by TNBS.

PURPOSE: PS-341 (bortezomib, Velcade), the first proteasome inhibitor approved by the Food and Drug Administration for the treatment of patients with relapsed multiple myeloma, induces apoptosis in human cancer cell lines. Vitamin C (ascorbic acid) is an essential water-soluble vitamin required for many normal physiologic functions and has to be obtained through diet or supplemental tablets in humans. Here we studied the potential effect of vitamin C on the anticancer activity of PS-341 in human cancer cell lines. EXPERIMENTAL DESIGN: The effects of vitamin C on apoptosis induction by PS-341 alone and by PS-341 combined with tumor necrosis factor-related apoptosis-inducing ligand were studied. In addition, the effects of vitamin C and other antioxidants on PS-341-mediated proteasome inhibition were also examined. Finally, the direct chemical interaction between vitamin C and PS-341 was determined. RESULTS: Vitamin C abrogated the ability of PS-341 to induce apoptosis in various human cancer cell lines, to induce G(2)-M arrest, and to augment apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand. Moreover, vitamin C suppressed PS-341-mediated inhibition of proteasome activity. PS-341 itself did not induce generation of intracellular reactive oxygen species whereas other antioxidants failed to abrogate its biological activity. Importantly, we detected a direct chemical interaction between vitamin C and PS-341. CONCLUSION: Vitamin C directly binds to PS-431, thus inactivating PS-341 independent of its antioxidant activity. Our findings suggest that vitamin C may have a negative effect on PS-341-mediated anticancer activity.

Epidemiological studies have suggested an association between vitamin C (and other antioxidant vitamins) and cancer risk. However, the mechanisms accounting for prevention have not been extensively investigated. In skin, vitamin C (ascorbic acid) exerts different biological roles, including photoprotective effects and participation in collagen synthesis. This paper reports new findings about additional functions of the vitamin. Vitamin C counteracts oxidative stress via transcriptional and post-translational mechanisms; this modulation may interfere with the activity of redox-sensitive transcription factors, commitment to differentiation or cell cycle arrest, and apoptosis in response to DNA damage. All of these vitamin C-mediated responses might be important in different cell types, allowing for the maintenance of body homeostasis.

DNA damage generated by oxygen-derived free radicals is related to mutagenesis, carcinogenesis and aging. In the last several years, hundreds of publications have confirmed that melatonin is a potent endogenous free radical scavenger. In the present in vitro study, we have examined the efficacy of three polyphenolic antioxidants, i.e. xanthurenic acid, resveratrol (3,4',5-trihydroxy-trans-stilbene) and (-)-epigallocatechin-3-gallate (EGCG) and two classical non-polyphenolic antioxidants, i.e. vitamin C (ascorbic acid) and alpha-lipoic acid (LA, 1,2-dithiolane-3-pentanoic acid) in inhibiting *OH-induced oxidative DNA damage. We compared the efficacy of these five antioxidants with the effectiveness of melatonin (N-acetyl-5-methoxytryptamine) and we also investigated the possible synergistic effects of melatonin with the other five molecules. Using high performance liquid chromatography (HPLC), the formation of 8-hydroxy-2-deoxyguanosine (8-OH-dG) in purified calf thymus DNA treated with the Fenton reagents, chromium(III) (as CrCl3) plus hydrogen peroxide (H2O2) (Cr(III)/H2O2), was measured in the presence or absence of the antioxidants alone or in combination with melatonin. 8-OH-dG is considered a biomarker of oxidative DNA damage. Among the antioxidants tested, melatonin was the most effective of these with an IC50 = 3.6 +/- 0.1 micro m. For the other antioxidants the IC50 values were as follows: xanthurenic acid (IC50 = 7.9 +/- 0.3), resveratrol (IC50 = 10.9 +/- 0.3), EGCG (IC50 = 5.7 +/- 0.3), vitamin C (IC50 = 16.9 +/- 0.5) and LA (IC50 = 38.8 +/- 0.7). These values differ from that of melatonin with a P < 0.01. Melatonin (1 micro M) reversed the pro-oxidant effect of resveratrol (0.5 micro M) and vitamin C (0.5 micro M), had an antagonistic effect when used in combination with EGCG (1 micro M) and it exhibited synergism in combination with vitamin C (0.5 micro M) and with LA (5 micro M).

The effects of vitamin C (ascorbic acid), vitamin E (alpha-tocopherol), and beta-carotene as antioxidants and their cooperative action against the oxidation of lipid in solution, membranes, and lipoproteins have been studied and reviewed. Ascorbic acid and alpha-tocopherol act as potent, and probably the most important, hydrophilic and lipophilic antioxidants, respectively. They function at their own site individually and furthermore act synergistically. beta-Carotene has lower reactivity toward radicals than does alpha-tocopherol and acts as a weak antioxidant in solution. It is more lipophilic than alpha-tocopherol and is assumed to be present at the interior of membranes or lipoproteins, which enables it to scavenge radicals within the lipophilic compartment more efficiently than does alpha-tocopherol. The cooperative interaction between vitamin C and vitamin E may be quite probable, that of vitamin C and beta-carotene is improbable, whereas that between vitamin E and beta-carotene may be possible.

57. Probl Khig. 1992;17:137-45. [The effect of elevated amounts of ascorbic acid on the status of the vitamin and lung disorders in guinea pigs inhaling styrene]. [Article in Bulgarian] Petrova S, Mikhaĭlova A, Donchev N. An inhalation intoxication with styrene is performed on guinea pigs--600 mg.m-3, 5 hrs daily, 5 days weekly for a period of 4 weeks. The animals are put on regime lacking vitamin C. Ascorbic acid is introduced orally on 3 levels: 20 mg.kg-1 body mass (control) and with increased quantities 60 mg.kg-1 and 240 mg.kg-1 body mass. On the third day the content of ascorbic acid in some biochemical parameters of the lung is determined. Histochemical examinations of the lung tissue are made. The styrene causes decrease in the ascorbic acid content in the lung, considerable increase of the studied enzymes (lactate- and glucose-6-phosphate-dehydrogenase, alkaline and acidic phosphatase) and the concentration of the total protein in the lung. There are inflammatory, dystrophic and obturation changes. The raised intake of ascorbic acid 60 mg.kg-1 body mass doesn't effect the negative influence of styrene. The high dose (240 mg.kg-1 body mass) provokes increased activity of the examined enzymes. At inhalation with styrene this dose of ascorbic acid increases the styrene effect on the enzyme activity, especially of LDH and glucose-6-phosphate-dehydrogenase, without invigorating the pathomorphological disturbances in the lung.

BACKGROUND: Sepsis and septic shock are severe medical conditions that can damage multiple organs with a higher risk of mortality. Recently, the combination of hydrocortisone, ascorbic acid and thiamine (HAT) was hypothesized to work synergistically to reverse septic shock and reduce mortality. AIM: To ascertain the efficacy of HAT therapy and compare whether HAT therapy is more beneficial compared to the standard of care in sepsis and septic shock patients. METHODS: PubMed, Clinicaltrials.gov, Scopus, Web of Science, Cochrane and Embase are databases that were used to identify trials that conducted a study of the combination of HAT in sepsis or septic shock. RESULTS: There were 134 articles identified through a database search and 16 from other sources, which were subsequently reduced to 11 trials (six randomized trials and five non-randomized trials) that were deemed appropriate for inclusion in this review. Most of the outcomes from these studies focused on mortality, the need for renal replacement therapy, duration of vasopressor use, changes in Sequential Organ Failure Assessment score, procalcitonin clearance and lengths of intensive care unit stay. CONCLUSION: Due to inconsistent results from clinical studies, the benefits of HAT therapy cannot be confirmed at this point in sepsis and septic shock. Currently, there are at least 20 randomized controlled trials testing HAT in various combinations and dosages in patients with severe sepsis and septic shock. The results of these studies are required before definitive conclusions can be made regarding the impact of this novel treatment strategy on the morbidity and mortality of patients with sepsis.

Vitamin C (ascorbic acid) is a water-soluble vitamin with an array of biological functions. A number of proposed factors contribute to the vitamin's plasma bioavailability and ability to exert optimal functionality. The aim of this review was to systematically assess plasma vitamin C levels post-surgery compared with pre-surgery/the magnitude and time frame of potential changes in concentration. We searched the PUBMED, SCOPUS, SciSearch and the Cochrane Library databases between 1970 and April 2020 for relevant research papers. Prospective studies, control groups and true placebo groups derived from controlled trials that reported means and standard deviations of plasma vitamin C concentrations pre- and postoperatively were included into the meta-analysis. Data were grouped into short-term (≤7 d) and long-term (>7 d) postoperative follow-up. Twenty-three of thirty-one studies involving 642 patients included in the systematic review were suitable for meta-analysis. Pooled data from the meta-analysis revealed a mean depletion of plasma vitamin C concentration of -17·99 µmol/l (39 % depletion) (CI -22·81, -13·17) (trial arms = 25, n 565, P < 0·001) during the first postoperative week and -18·80 µmol/l (21 % depletion) (CI -25·04, -12·56) (trial arms = 6, n 166, P < 0·001) 2-3 months postoperatively. Subgroup analyses revealed that these depletions occurred following different types of surgery; however, high heterogeneity was observed amongst trials assessing concentration change during the first postoperative week. Overall, our results warrant larger, long-term investigations of changes in postoperative plasma vitamin C concentrations and their potential effects on clinical symptomology.

Many cancer patients on intensive chemotherapy lack vitamin C. Vitamin C stimulates the production and activation of immune cells, so perhaps supplementation could be used to improve the immunity in those patients. This review assesses the effectiveness and safety of vitamin C administration in cancer. The PubMed and EMBASE databases were searched and all study designs except for phase I studies, and case reports were included in this review. A total of 19 trials were included. In only 4 trials randomization was used to determine if patients received vitamin C or a placebo. The result of this review does not prove that there is a clinically relevant positive effect of vitamin C supplementation in cancer patients in general on the overall survival, clinical status, quality of life (QOL) and performance status (PS), since the quality of the studies published is low. Interventions and patient groups are very diverse, hence an effect in some patient groups is possible. There seems to be a better effect with intravenous than oral administration. Nevertheless, treatment with vitamin C is safe with minimal side effects. Thereby, we think it is safe to examine the effects of vitamin C on specific groups of patients in a randomized controlled setting.

Peripheral tolerance depends on limiting conventional T cell responses to self-antigens. To define the contribution of nutritional factors and related epigenetic regulation, we perform in vivo CRISPR screening and identify the ascorbate transporter Slc23a2 as a key regulator of naive T cell (Tn) reactivity. T cell-specific loss of Slc23a2 reduces intrace

OBJECTIVES: Ferroptosis is a distinct form of programmed cell death characterized by iron (Fe)-dependent oxidative stress and the accumulation of intracellular reactive oxygen species. Cisplatin (CPT), a chemotherapeutic agent, can induce ferroptosis in glioma cells and act synergistically with erastin (EST). The total extract of the fungus Sanghuangporus vaninii (TSV) has anticancer and antioxidant activities. This investigation aimed to assess the properties of TSV on CPT-induced inflammatory response and ferroptosis-related changes in glioma cells. METHODS: LNZ308 glioma cells were exposed to CPT and EST, followed by treatment with different TSV concentrations. Cell viability was assessed. Intracellular reactive oxygen species (ROS), glutathione peroxidase 4 (GPX4), glutathione (GSH), labile iron pool (LIP), LPO, interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were examined, and cell migration was assessed using a scratch assay. RESULTS: TSV (25 µg/mL) exhibited limited toxicity to LNZ308 cells but failed to reverse the CPT-induced loss of cell viability. TSV markedly reduced ROS levels, LIP, and LPO, while restoring GSH and GPX4 levels. Moreover, it diminished IL-1β, TNF-α, and IL-6 in CPT-treated LNZ308 cells in a dose-responsive manner. L-ascorbic acid diminished ROS levels during oxidative stress. TSV also promoted scratch closure in both untreated and CPT-treated LNZ308 cells. CONCLUSION: The results indicate that TSV modulates CPT-induced oxidative, inflammatory, and ferroptotic responses in LNZ308 glioma cells in vitro, supporting further investigation of its potential as an adjunct to chemotherapy. © The Author(s) 2026.

Although the extracellular matrix (ECM) is a highly dynamic partner of the immune system, its immunoregulatory role during the early phase of sepsis-induced acute lung injury (ALI) remains poorly defined. Using a murine cecal ligation and puncture (CLP) model, we observed dynamic ECM remodeling characterized by rapid collagen loss within 24 h, followed by a pathological fibroproliferation phase. Proteomic profiling of the degraded ECM demonstrated its immunoregulatory potential. In vitro studies revealed that annexin A1 (ANXA1), an upregulated ECM component, promoted anti-inflammatory macrophage polarization via the formyl-peptide receptor 2/lipoxin A4 (FPR2/ALX)-dependent 5'-adenosine monophosphate-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) pathway. However, under pathological conditions, collagen loss markedly reduces the number of key binding sites for integrin β1 (Itgb1), thereby disrupting macrophage-ECM adhesion and resulting in macrophage detachment; upon entering the inflammatory microenvironment, these cells acquire a proinflammatory phenotype, exacerbating pulmonary inflammation. Capitalizing on the collagen biosynthetic function of ascorbic acid (AA), we investigated its capacity to restore macrophage-ECM adhesion therapeutically. In vitro, treatment of fibroblasts with AA on decellularized CLP-ECM increased collagen deposition and improved macrophage adhesion. In vivo, intratracheal instillation of AA (20 mg/kg) enhanced collagen biosynthesis, which promoted ECM restoration, sustained interstitial macrophage retention, suppressed proinflammatory cytokine production, and ultimately resolved lung injury. Our study reveals that ECM degradation is an early immunoregulatory event and suggests a therapeutic approach for ECM repair via airway-targeted AA delivery in ALI. © 2026. Science China Press.

BACKGROUND: Acute kidney injury (AKI) is associated with increased morbidity, prolonged hospitalization, and mortality, particularly in high-risk patients. OBJECTIVES: This study aimed to evaluate the potential reno-protective effects of Tadalafil, a selective phosphodiesterase-5 (PDE-5) inhibitor, alone and in combination with ascorbic acid, in a cisplatin-induced AKI rat model. METHODS: Thirty male albino rats (250-300 g) were randomly divided into five groups: control (A), cisplatin-treated (B), ascorbic acid-treated (100 mg/kg) (C), Tadalafil-treated (5 mg/kg) (D), and combined ascorbic acid + Tadalafil (E). Treatments were administered for 10 days prior to a single intraperitoneal dose of cisplatin (10 mg/kg). After 72 h, blood and kidney tissue samples were collected for biochemical and histopathological analyses. Serum urea and creatinine, as well as renal tissue levels of NGAL, SOD, and TNF-α, were evaluated. RESULTS: Cisplatin significantly increased urea, creatinine, TNF-α, and NGAL levels, while reducing SOD compared to control. Pre-treatment with Tadalafil, alone or in combination with ascorbic acid, significantly ameliorated these alterations. CONCLUSIONS: Tadalafil in combination with ascorbic acid shows enhanced protective effects, suggesting greater protective effect role. Further studies are required to confirm its clinical applicability. © 2026 Walter de Gruyter GmbH, Berlin/Boston.

Mesoporous platinum nanoarchitectures are attractive functional nanomaterials (e.g., high performance nanozymes), yet sub-20 nm Pt nanoparticles with coating-free surfaces and fully accessible porous structures remain difficult to obtain because most synthetic routes rely on surfactants, polymers, sacrificial metals, or structure-directing agents that poison Pt catalytic surface whilst also impeding access to pores. Here, we report a one-pot aqueous, template-free synthesis of mesoporous Pt nanoparticles enabled by temperature/pressure control in sealed microwave reactors, using only ascorbic acid and citrate as reducing agent and small, removable surface coating, respectively. HAADF-STEM tomography evidences a porous architecture with internal voids distributed throughout the nanoparticle volume, while electrochemical measurements confirm an enhanced electrochemically active surface area consistent with high pores accessibility. The nanoparticles exhibit good dispersion under biologically relevant conditions and efficient cellular uptake, with no cytotoxicity in RAW 264.7 macrophage-like cells. Functionally, these mesoporous Pt nanozymes attenuate LPS-induced oxidative stress and reduce IL-6 secretion, demonstrating potent antioxidant/anti-inflammatory activity. In an in vitro model of atherosclerosis, they further decrease oxidized-LDL uptake and foam-cell formation, indicating a multi-level mitigation of ROS-driven macrophage dysfunction. Overall, this work establishes a straightforward route to clean, sub-20 nm mesoporous Pt nanozymes and highlights their potential for modulating inflammation in ROS-driven diseases.

Plants have served as important sources of medicine since prehistoric times, forging a strong connection between humans and their environment. This relationship has yielded valuable insights into the therapeutic use of herbs for various health conditions. The current study aims to gather scientific evidence about traditional Indian anti-aging herbal beverages that have been practiced for centuries. We conducted a literature search through online databases, research articles, search engines, and books, covering the period from 2000 to February 2025. We examined 1221 articles and selected 53 from 298 for the most relevant information. The secondary metabolites of these traditional beverages interact with key biological functions and develop polarization with the ability to combat bacteria, reduce inflammation, eliminate harmful reactive oxygen species (ROS), and influence aging. Ascorbic acid, kempferol, quercetin, β-carotene, and chlorogenic acid were found in three or more beverages we screened in the present investigation. These beverages contribute to cell functions, lower oxidative stress, prevent chronic diseases, and reduce inflammation. The strong therapeutic potential of these beverages, combined with their low toxicity, has led to widespread public acceptance and highlighted the need for further research. Although certain beverages share common ingredients, understanding their functional molecular mechanisms is limited. Network pharmacological studies have identified a module of 22 nodes linked to the anti-aging effects of these beverages. Additionally, clinical trials may help create new food supplements and modern green medicines.

Astaxanthin, a potent antioxidant carotenoid, exhibits significant therapeutic potential, however its broader biomedical application is limited by chemical instability, poor aqueous dispersibility, and limited bioavailability. Lipid-based nanocarriers, particularly deformable vesicular systems such as transfersomes, offer a promising strategy to overcome these limitations. In this study, astaxanthin-loaded phosphatidylcholine transfersomes were developed using sodium deoxycholate, Tween 80, or D-α-tocopherol polyethylene glycol 1000 succinate as edge activators, in combination with either ascorbyl palmitate or sodium ascorbyl phosphate as co-antioxidants. All formulations yielded nanosized vesicles with narrow size distributions (87-124 nm) and high entrapment efficiencies (>87%). In the optimized Tween 80-based system, the choice of co-antioxidant significantly influenced colloidal stability and astaxanthin retention, with ascorbyl palmitate preserving 87% of astaxanthin after 4 weeks. The vesicles demonstrated strong radical-scavenging activity comparable to free astaxanthin and showed no cytotoxicity at physiologically relevant concentrations in NIH/3T3 fibroblasts and RAW 264.7 macrophages. Furthermore, the optimized formulations effectively reduced intracellular reactive oxygen species in human neutrophils and suppressed nitric oxide and TNF-α production in macrophages more efficiently than non-encapsulated astaxanthin. Collectively, these findings indicate that incorporation of astaxanthin with ascorbyl palmitate into deformable vesicular carriers enhances its physicochemical stability and potentiates anti-inflammatory redox activity, highlighting transfersomes as an effective platform for the delivery of redox-active carotenoids.

BACKGROUND: Personalized antioxidant supplementation is promoted to optimize redox balance and inflammation profile. OBJECTIVE: To quantify the short-term effects of vitamin C supplementation on redox and inflammatory outcome measures and explore the potential for supplement response heterogeneity in participants with vitamin C inadequacy through aggregated sets of multi-cycle n-of-1 trials. METHODS: Eight healthy young males (age 25.56 ± 3.15 years, body mass 68.24 ± 9.70 kg) completed four supplementation (vitamin C 1g) and four placebo trials administered on repeated occasions in randomized sequences following a 1-month run-in period. Vitamin C, F2-isoprostanes, interleukin-6, and tumor necrosis factor-α were assessed as primary outcomes. Separate within-participant linear mixed-effects modelling and meta-analytic models estimated replicate-averaged treatment effects and person-by-treatment response variation to vitamin C supplementation. RESULTS: Supplementation resulted in a statistically significant increase in plasma vitamin C of 20.6 μmol/L (95% confidence interval [CI]: 16.8 to 24.5). This mean treatment effect was lower than our selected clinically important threshold of 23 μmol/L. Vitamin C supplementation reduced F2-isoprostanes by 25.9 pg/mL (CI: 22.2 to 29.6 pg/mL), interleukin-6 by 1.2 pg/mL (CI: 0.7 to 1.7 pg/mL), and tumor necrosis factor-α by 0.5 pg/mL (CI: 0.2 to 0.9 pg/mL). The participant-by-treatment variance component from linear mixed-effects modelling was not statistically significant for all outcomes (P > 0.05), agreeing with the small τ-statistics for all outcomes. Shrinkage-adjusted estimates also showed strong shrinkage toward the mean, indicating that the observed response variation mainly reflected random within-person cycle-to-cycle variability rather than true inter-individual variability. CONCLUSIONS: Replicate-averaged treatment effects of vitamin C supplementation on our study outcomes were statistically significant, but heterogenous treatment effects were not detected between participants with baseline inadequacy. Cycle-to-cycle within-participant variation was larger than the observed inter-individual variability for each pr

Tendons are specialized connective tissues that transmit mechanical forces from muscle to bone, ensuring joint stability and efficient locomotion. Their homeostasis and regenerative capacity depend on the interplay between extracellular matrix (ECM), resident and recruited cell populations, and immune-mediated signaling. This review provides an overview of tendon structure and composition, emphasizing the collagen-based organization and the functional role of non-collagenous matrix components in mechanotransduction and cell signaling. The heterogeneity of tendon-resident cells, including tenocytes, tendon stem/progenitor cells, and vascular- and immune-associated cells, is discussed, highlighting their roles in tissue maintenance, adaptation, and repair. Tendon aging is characterized by altered cellular responsiveness, ECM disorganization, and reduced capacity to resolve inflammation, predisposing tissues to degeneration and chronic tendinopathies. Emerging evidence underscores the central role of the immune response in both inflammatory and healing processes. Key bioactive compounds used in tendinopathy management, such as collagen, vitamin C, vitamin D, methylsulfonylmethane, hyaluronic acid, and manganese, are discussed regarding their mechanistic effects on collagen synthesis, matrix remodeling, oxidative stress, immune modulation, and cell-matrix interactions. Overall, tendon health emerges from a dynamic balance between structural integrity, cellular activity, and immune regulation, supporting the rationale for targeted nutritional strategies to promote tendon homeostasis and regeneration.

Neurodegenerative diseases involve the convergence of cholinergic dysfunction, neuronal loss, and sustained neuroinflammatory responses, necessitating the development of multifunctional therapeutic agents. In this study, a series of novel thieno[3,2-d]pyrimidine-phenolic Mannich base hybrids were rationally designed, synthesized, and evaluated as dual cholinesterase inhibitors with neuroprotective and anti-neuroinflammatory potential. The synthesized compounds exhibited potent inhibition against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with inhibition constants in the low nanomolar range. Among them, compounds 5 and 9 emerged as the most active derivatives, displaying Ki values of 8.79 and 14.11 nM for AChE and 7.04 and 11.75 nM for BChE, surpassing the reference inhibitors tacrine and donepezil. Molecular docking and molecular dynamics simulations supported the experimental findings, and Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) binding free energy calculations further confirmed their superior binding affinities compared with donepezil. Cytotoxicity profiling in SH-SY5Y neuronal cells and RAW 264.7 and THP-1 immune cells identified a narrow sub-cytotoxic concentration window (EC05-EC10 = 1.2-2.1 μM), ensuring biological effects independent of nonspecific cell damage. Within this range, both compounds exerted pronounced anti-neuroinflammatory activity. Notably, compound 9 significantly downregulated pro-inflammatory mediators, reducing IL-1β, IL-6, and NF-κB1 gene expression by up to 2.78-, 3.37-, and 4.84-fold, respectively. Consistently, it suppressed nitric oxide production in LPS-stimulated macrophages to levels comparable with ascorbic acid and markedly decreased Iba1 expression in activated THP-1 cells. This integrated enzymatic, computational, and cellular investigation identifies compounds 5 and 9 as promising multifunctional lead combining dual cholinesterase inhibition with robust anti-neuroinflammatory activity. The results provide a strong foundation for future in vivo studies and further optimization toward disease-modifying agents for neurodegenerative disorders.

This study examined the effects of vitamin C on oxidative stress, antioxidant levels, and periodontal inflammation in a rat model of periodontitis exposed to cigarette smoke. Periodontitis was induced in 30 male Wistar albino rats using ligatures on maxillary second molars. All groups underwent 15 days of smoke exposure, which was then continued for another 15 days in the smoking-only (SO) and smoking + vitamin C. The vitamin C group received 200 mg/kg/day of intraperitoneal vitamin C; the saline group received 0.9% NaCl. On Day 28, rats were euthanized for biochemical and immunohistochemical analyses. The SO group showed significantly elevated cotinine and tumor necrotizing factor-α levels. Reactive oxygen species, thiobarbituric acid reacting substances, and catalase activity were also significantly higher in this group. Vitamin C groups showed lower levels, with no significant differences between them. Ferric-reducing antioxidant power levels in the saline group were significantly higher than in the SO group. Immunohistochemical analysis revealed significant differences in Ki-67 and matrix metalloproteinase-8-positive-stained cells between SO and vitamin C groups. Within the limitations of this model, vitamin C supplementation was associated with reduced oxidative stress and inflammatory responses in smoke-exposed rats with periodontitis. These results suggest vitamin C may modulate host antioxidant defense, though further clinical confirmation is needed. © 2026 Scandinavian Division of the International Association for Dental Research. Published by John Wiley & Sons Ltd.

Comment in World J Mens Health. 2026 Jul;44(3):749-750. doi: 10.5534/wjmh.250314. Benign prostatic hyperplasia and prostate cancer (PC) frequently affect aging men, both involving irregular cell growth in the prostate. Inflammation is a major contributor to these conditions, whereas DNA methylation and hydroxymethylation are specifically involved in PC development. In this review, we address several potential factors influencing the progression of PC, including DNA epigenetic marks, ascorbate (vitamin C) concentration in the blood plasma, and its intracellular levels in leukocytes and prostate tissues. Moreover, a new aspect concerning the involvement of leukocytes (white blood cells) in PC formation will also be discussed, highlighting their potential utility for assessing early PC development through a minimally invasive approach.

BACKGROUND: Successful management of an avulsed tooth depends on preserving periodontal ligament viability during the extraoral period. Although Hank's Balanced Salt Solution (HBSS) is recommended for storage of avulsed teeth, it lacks bioactive components that actively support tissue repair. This study evaluated whether supplementation with L-ascorbic acid (L-AA) could enhance biological responses associated with periodontal healing. MATERIAL AND METHODS: Complementary in vitro and ex vivo models were used. Cultured human periodontal ligament cells were exposed to HBSS, HBSS supplemented with L-AA, or Dulbecco's Modified Eagle Medium containing fetal bovine serum. Wound closure, inflammatory cytokine expression, matrix metalloproteinase expression, and collagen type I alpha 1 chain gene and protein expression were evaluated. In the ex vivo model, 18 freshly extracted premolars were stored in the respective media for 24 h at 4°C before assessment of periodontal ligament tissue viability and gene expression. Statistical significance was set at p < 0.05. RESULTS: The optimized concentration of L-AA was 175 μg/mL. Supplementation of HBSS with L-AA resulted in significantly greater wound closure than HBSS alone. In both in vitro and ex vivo models, L-AA supplementation significantly reduced the expression of pro-inflammatory cytokines and matrix metalloproteinases while enhancing the expression of collagen type I alpha 1 chain. Although periodontal ligament tissue viability was numerically higher following supplementation, differences were not statistically significant. CONCLUSIONS: Supplementation of HBSS with L-AA favorably modulated inflammatory and extracellular matrix-related responses in cultured and ex vivo periodontal ligament tissues. Although no significant improvement in tissue viability was observed, the findings suggest potential biological benefits relevant to periodontal repair. Further studies are required to validate these findings in animal replantation models and determine their clinical relevance. © 2026 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

AIM: Obesity is commonly associated with skeletal muscle atrophy and is attributed to chronic inflammation, oxidative stress, and impaired adipose-muscle cross talk. Ascorbic acid, a potent antioxidant and its role in obesity induced muscle atrophy is not clearly understood. Hence, the aim of the study was to rescue obesity induced skeletal muscle atrophy with ascorbic acid in vitro. MATERIALS AND METHODS: C3H10T1/2 mesenchymal stem cells were developed into obesogenic adipocytes by palmitic acid treatment to generate obesogenic adipocyte-conditioned media (ObCM). C2C12 myoblasts and differentiated myotubes were treated with ObCM in the presence or absence of ascorbic acid (AsA). Cell viability and reactive oxygen species generation were evaluated by MTT assay and DCFDA staining. Gene and protein expression analyses were performed using quantitative real-time PCR and western blotting. Statistical significance was determined using one-way ANOVA with Tukey's post hoc test. KEY FINDINGS: In the present study, we have established a palmitic acid induced hypertrophic adipocyte model using C3H10T1/2 mesenchymal stem cells and generated obese conditioned medium to replicate obese microenvironment. Differentiated C2C12 myotubes when exposed to obese conditioned media resulted in reduced myotube diameter, increased expression in ROS, inflammatory cytokines, activation of ubiquitin proteasome system and upregulated muscle atrophy genes. Treatment with Ascorbic acid significantly mitigated ROS generation, reduced inflammatory cytokines, and restored myogenic protein expression associated with modulation of NF-κB signalling. SIGNIFICANCE: Our findings suggest that ascorbic acid alleviates adipocyte-derived inflammatory stress and protects against myotube atrophy, highlighting its therapeutic potential in obesity-associated muscle wasting.

Vitamin C (L-ascorbic acid) is an essential micronutrient involved in collagen biosynthesis, redox regulation, immune function, endothelial biology, carnitine synthesis, neurotransmitter metabolism, and non-heme iron absorption. Dietary reference values are designed primarily to prevent deficiency in general populations, but vulnerability to low-vitamin C status may increase during trauma, surgery, chronic inflammation, malignancy, metabolic disease, smoking, poor intake, environmental exposure, and tissue repair. This narrative review synthesizes mechanistic, pharmacokinetic, clinical, and safety evidence on vitamin C as a stress-responsive micronutrient. Evidence is reviewed across tissue repair and wound healing, orthopedic recovery and selected complex regional pain syndrome risk contexts, fatigue, neuropsychiatric vulnerability, cancer-supportive care, vascular homeostasis, dermatologic biology, and preliminary microbiota-gut-brain axis hypotheses. The strength of evidence differs substantially across domains: biochemical functions and deficiency correction are well established, whereas benefits of supraphysiologic oral supplementation in vitamin C-replete patients remain uncertain. Oral nutritional supplementation is distinguished from intravenous pharmacologic ascorbate, with attention to route, formulation, dose division, gastrointestinal tolerance-limited adjustment, and safety monitoring. Because evidence for high-dose oral supplementation remains limited and condition-specific, such use should be individualized, time-limited, and clinician-monitored rather than presented as a population-level recommendation or evidence-defined therapeutic target. Taken together, the clinical value of vitamin C depends on baseline status, patient vulnerability, route, formulation, dosing interval, clinical endpoint, and safety review.

OBJECTIVES: Vitamin C has gained interest as an adjunctive treatment in oncology due to its antioxidant effects, potential to enhance cancer therapy, and ability to improve quality of life. This systematic review and meta-analysis aimed to assess the therapeutic impact of vitamin C in patients with solid and hematologic malignancies. METHODS: A comprehensive search was conducted in PubMed, Cochrane, Embase, ClinicalTrials.gov, and Google Scholar from inception to August 2025, in accordance with PRISMA guidelines. A total of 43 studies were included, with 19 focusing on hematologic malignancies (695 patients) and 24 on solid tumors (827 patients). Data were extracted and analyzed using Kaplan-Meier survival plots via the MetaSurvival package (R version 4.2.1; R Foundation for Statistical Computing, Vienna, Austria). Selected studies were also described narratively. RESULTS: In hematologic malignancies, the median age was 60.92 years, and 49.07% were male. The pooled median overall survival (mOS) was 34.42 months, and median progression-free survival (mPFS) was 14.09 months (95% CI: 9.54-20.50). The estimated mean OS and PFS were 27.80 months (95% CI: 22.78-31.58) and 19.63 months (95% CI: 15.97-22.53), respectively. Among solid tumors, pancreatic cancer showed a mOS of 15.2 months and lung cancer 13.4 months. Vitamin C was also associated with reduced inflammation, oxidative stress, and radiotherapy-related side effects, as well as improved quality of life. CONCLUSIONS: Vitamin C may enhance tolerability and patient-reported outcomes in cancer therapy. While survival benefits were observed in hematologic malignancies, evidence remains inconsistent in solid tumors, underscoring the need for larger, well-designed trials.

High-dose intravenous vitamin C (HDIVC) has been investigated as a potential adjunctive therapy in critical illness, including sepsis, acute respiratory distress syndrome (ARDS), and COVID-19. Despite a strong mechanistic rationale, clinical trials have yielded inconsistent results. From a clinical pharmacology perspective, this variability may reflect, at least in part, differences in pharmacokinetic exposure, timing of administration, and patient selection rather than a lack of biological activity. Intravenous administration enables plasma concentrations in the millimolar range (≈1-5 mM), far exceeding those achievable with oral dosing (<100 µM), thereby reaching thresholds required for pharmacodynamic effects on oxidative stress, immune signaling, and endothelial function. This exposure-dependent transition distinguishes vitamin C as a pharmacological agent rather than a nutritional supplement in critically ill populations. Therapeutic response may be influenced by timing relative to disease progression, with earlier administration representing a biologically plausible strategy that warrants prospective evaluation rather than a clinically established therapeutic window. Interindividual variability in transporter function, redox status, and genetic background may further contribute to heterogeneous responses. Biomarkers such as interleukin-6 (IL-6), C-reactive protein (CRP), D-dimer, and markers of endothelial injury provide a framework for patient stratification and monitoring of pharmacodynamic effects. Integrated with pharmacokinetic principles, these markers support a shift toward biomarker-guided, precision-based therapeutic strategies. This review synthesizes current clinical and mechanistic evidence through an exposure-response conceptual framework, framing HDIVC as a context-dependent pharmacological intervention and advancing a shift toward biomarker-guided, precision-based therapeutic strategies in critical illness.

Healing a skin wound is a complex biological process that proceeds through three stages: inflammation, proliferation, and remodeling. Hyaluronic acid (HA) and vitamin C may help tissues heal in different but complementary ways. This study aimed to examine and compare the effects of HA and vitamin C, alone and in combination, on collagen-related histological and immunohistochemical repair indices at day 22 in a rat sutured incisional wound model. Twenty adult male albino rats were divided into four equal groups (n = 5/group) at random: the control, vitamin C-treated, HA-treated, and combined HA + vitamin C-treated groups. Each animal received a standardized sutured full-thickness cutaneous incision to model primary-intention wound healing. Treatments were administered daily for 21 days using different administration routes: topical HA, oral vitamin C, or their combined regimen; wound tissue was collected on day 22 to evaluate late histological and immunohistochemical repair outcomes after completion of the treatment period. Hematoxylin and eosin, Masson's trichrome, and collagen type I immunohistochemistry were used to evaluate collagen-related histological and immunohistochemical repair features. Collagen type I expression, collagen deposition, and fibroblast count were quantified by morphometry. The H&E-based fibroblast-like cell count showed an exploratory between-group difference in the primary ANOVA analysis (p = 0.039), with the HA + vitamin C group having the highest mean; however, pairwise significance was limited to the comparison with the water-treated group, and the non-parametric sensitivity analysis was more conservative. Collagen deposition was higher in the combined-treatment group than in the water, HA-alone, and vitamin C-alone groups, and the difference was significant (p < 0.001). Additionally, collagen type I expression varied significantly (p = 0.003), with the HA + vitamin C group having the highest mean area percentage and significant pairwise differences compared to the water and vitamin C groups. At day 22, the combined HA + vitamin C regimen showed the highest collagen deposition and collagen type I immunopositive area among the tested g

INTRODUCTION: The identification of microbial strains harbouring bioactive genes is important for the discovery of novel therapeutic agents. The study objective was to identify the genes in Kurthia gibsonii VITAM20 that are associated with anti-inflammatory and antioxidant properties and validate these findings with in vitro functional assays. METHODS: Genes associated with anti-inflammatory and antioxidant activities were identified by BLAST analysis against curated databases. The anti-inflammatory, antioxidant, and antibacterial potential of Kurthia gibsonii VITAM20 were subsequently evaluated using in vitro assays. RESULTS: BLAST analysis identified several genes associated with anti-inflammatory properties, including eps (95.455%), NEMO (100%), spa (100%), and spaB (90.625%). Multiple genes associated with antioxidant potential were also detected, including CAT (92.308%), dps (95.238%), gshR3 (91.304%), gshR4 (100%), KATA (100%), oxyR (100%), KatA (88.462%), perR (74.041%, bit score 126), sodA (100%), sodM (76.471%), and trxA (77.778%). The genomic findings were supported by in vitro analyses, which demonstrated notable anti-inflammatory activity. Kurthia gibsonii VITAM20 exhibited human red blood cell membrane stabilization rates of 90.78% ± 1.03% and 69.92% under non-heated and heated conditions, respectively, compared with diclofenac (83.01% ± 0.72% and 83.83% ± 1.23%). In the egg albumin denaturation assay, Kuthia gibsonii VITAM20 demonstrated a concentration-dependent increase in inhibition from 80.94% ± 0.57% to 84.47% ± 0.39%, comparable to that of diclofenac. Furthermore, Kurthia gibsonii VITAM20 exhibited 64.27% ± 0.46% antioxidant activity compared with ascorbic acid (91.40% ± 0.46%), with an IC50 value of 286.5 µg/mL. The crude enzyme extract demonstrated antibacterial activity against Listeria monocytogenes and Staphylococcus aureus, producing inhibition zones of 13 mm. The MIC was determined to be 250 µg/mL for both pathogens. At this concentration, the crude enzyme extract inhibited the growth of L. monocytogenes and S. aureus by 81.46% and 77.82%, respectively. DISCUSSION: The combined genomic and functional analyses confirmed the presence of

This study assessed the impact of gallic acid plus vitamin C on systemic oxidant stress, inflammation, hepatic and renal histology of rats with type 2 diabetes mellitus. Twenty five albino male rats were allotted into five categories of five rats each and treated hereafter as: control and diabetic group (fed rat diets and water), vitamin C (diabetic treated rats administered vitamin C, 50 mg/kg), gallic acid (diabetic treated rats administered gallic acid at 20 mg/kg), gallic acid plus vitamin C (diabetic treated rats administered 20 mg/kg gallic acid and 50 mg/kg vitamin C). The study duration was forty two days. The diabetic group had significant raise (P<0.05) of fasting glucose, glycated hemoglobin, insulin resistance scores, oxidative stress and inflammatory markers (in the liver, kidney and serum), alteration of relative liver and kidney weights, liver and kidney function indices, significant decrease (P<0.05) in total hemoglobin, serum insulin, insulin sensitivity and pancreatic beta cell function scores, body weights and pathological changes in their liver and kidney histology. These changes were ameliorated following supplementation of the diabetic group with gallic acid, vitamin C and gallic acid plus vitamin C combined treatment. Intervention with vitamin C was more efficacious than gallic acid. However, combined treatment of gallic acid plus vitamin C was more efficacious than the single treatments in modulating systemic and local oxidative stress, inflammation and in restoring the altered liver and kidney histology of the diabetic rats. Key words Antioxidants " Type 2 diabetes mellitus " Diabetic liver disease " Diabetic kidney complication " Natural products.

Repairing ultralong peripheral nerve defects remains a major clinical challenge, primarily due to the requirement for regenerative platforms to be capable of integrating spatial guidance with temporally resolved biochemical cues. To address this, we developed a clinically translatable, fully synthetic nerve conduit that aligns with native regenerative principles through hierarchical microtopological engineering and phase-specific molecular delivery. This design creates a proregenerative microenvironment by synchronizing structural cues with repair cascades. The neuroanatomically inspired core mimics the endoneurium and perineurium, providing extensive cell-scale contact guidance for axonal alignment and fasciculation. A dual-layered sheath ensures mechanical integrity, metabolic permeability, and selective exclusion of fibrotic tissue. Tailored to align with distinct phases of nerve repair, the conduit enables sequential release of spermidine and ascorbic acid. Spermidine resolves early inflammation, priming the niche for ascorbic acid-mediated debris clearance, axonal elongation, and remyelination. In both rat (2 centimeters) and beagle (5 centimeters) models of critical-sized sciatic nerve defects, the conduit supports structural and functional regeneration comparable to autografts while yielding superior outcomes in motor coordination and suppression of autotomy. This strategy offers a scalable and mechanistically informed solution for repairing ultralong nerve injuries with high translational promise.

Intravenous (IV) vitamin C has been proposed as an adjuvant therapy in sepsis/septic shock due to its biological plausibility and safety profile, but the proliferation of reviews has not resolved its clinical utility. To synthesize the evidence on IV vitamin C (monotherapy, HAT-hydrocortisone+vitamin C+thiamine-and vitamin C+thiamine) in adults with sepsis/septic shock, prioritizing 28-30-day mortality. Umbrella review of systematic reviews and meta-analyses (MEDLINE/PubMed, Embase, Scopus, and Web of Science, without language restriction). Quality was assessed with AMSTAR 2, overlap with CCA, and when available, TSA and component/network meta-analysis (CINeMA). Certainty of evidence was graded using GRADE with an anchor estimator per outcome and regimen. Thirty-one reviews were included (30 quantitative: 28 SR/MA and 2 component/network MA; 1 qualitative). Combinations (HAT and vitamin C+thiamine) did not reduce mortality; hemodynamic improvements (small decreases in ΔSOFA and vasopressor hours) were modest, did not translate into survival benefits, and were primarily attributable to the corticosteroid. Monotherapy showed a possible mortality benefit signal under specific conditions (initiation ≤24 h, intermediate dose 25-100 mg/kg/day, 3-4-day courses; more pronounced in sepsis than shock), but with low-to-moderate certainty due to heterogeneity, imprecision, publication bias, and very high overlap among reviews. Combination regimens (HAT and vitamin C plus thiamine) did not reduce mortality; hemodynamic improvements were modest, did not translate into survival benefits, and were primarily attributable to the corticosteroid component. For monotherapy, a possible mortality benefit signal was identified under specific conditions (initiation within 24 h, intermediate dose 25-100 mg/kg/day, 3-4-day courses, more pronounced in sepsis than shock), but overall certainty remains low-to-moderate due to heterogeneity, imprecision, publication bias, and very high overlap among reviews. These findings do not support routine use of IV vitamin C in any regimen; for monotherapy, the identified signal warrants rigorous multicenter trials in well-defined clinical scenarios bef

BACKGROUND: Atrial fibrillation (AF) is a prevalent arrhythmia associated with chronic inflammation and metabolic dysregulation. Metabolic and inflammatory pathways may influence atrial electrophysiology and structural remodeling, contributing to AF onset and persistence, yet key circulating signatures remain poorly defined. OBJECTIVE: The purpose of this study was to characterize systemic inflammatory markers and circulating metabolomic profiles in patients with paroxysmal and persistent AF compared with non-AF controls. METHODS: In this prospective study, 101 patients were enrolled (mean age 59.9 ± 14.7 years; 73/101 [72%] male), including 41 with paroxysmal AF, 30 with persistent AF, and 30 controls. Fasting plasma samples were analyzed using targeted gas chromatography-mass spectrometry to quantify 156 metabolites and multiplex flow cytometry to profile 13 inflammatory cytokines. RESULTS: Interleukin-18 (IL-18) concentrations were significantly elevated in patients with AF compared with controls (P = .009), with highest levels observed in those with persistent AF. No significant differences were observed in IL-6 or high-sensitivity C-reactive protein. 9 metabolites showed significant differential abundance between patients with AF and controls. Metabolites including pyridoxine, N-acetylglutamine, 3-dehydroquinate, d-glucose, glucosamine, ascorbic acid, and galacturonic acid were reduced in AF, while capric acid and caprylic acid were elevated. β-Alanine was the only metabolite increased in persistent AF relative to both patients with paroxysmal AF and controls. Trimethylamine-N-oxide concentrations did not differ significantly between groups. CONCLUSION: This study identifies distinct metabolic and inflammatory signatures in AF, with IL-18 and specific energy-related metabolites emerging as potential markers of disease phenotype. These hypothesis-generating findings warrant validation in larger cohorts. Crown Copyright © 2026 Published by Elsevier Inc. on behalf of Heart Rhythm Society.

Vitamin C deficiency also known as scurvy, can present with musculoskeletal pain, gingival bleeding, oral discomfort, and impaired mobility. Children with Autism Spectrum Disorder (ASD) are at increased risk of vitamin C and other nutritional deficiencies due to sensory sensitivity and food selectivity. This report aims to describe two pediatric patients with nonverbal ASD who presented with oral and systemic symptoms. These cases highlight the importance of obtaining a detailed dietary history and complete examination when evaluating unexplained oral bleeding, gingival inflammation, and limb pain in children with ASD. Interdisciplinary collaboration among pediatric medicine, dentistry, and specialists is essential to ensure timely diagnosis and avoid unnecessary interventions. Increased clinical awareness of nutritional deficiencies and their oral manifestations can improve outcomes and reduce diagnostic delays in this vulnerable population. © 2026 Special Care Dentistry Association and Wiley Periodicals LLC.

Background/Objectives: Sarcopenia is characterized by progressive skeletal muscle loss and impaired myogenic differentiation and is closely associated with inflammation and metabolic dysfunction. Methods: This study investigated the protective effects of Momordica charantia extract against dexamethasone-induced sarcopenia and explored the underlying mechanisms using network pharmacology, C2C12 cell-based assays, Western blotting, and molecular docking. Network pharmacology analysis identified quercetin, ascorbic acid, and tocopherol as major active compounds associated with targets related to inflammation, extracellular remodeling, and metabolic dysfunction. Results: M. charantia extract (MCE) did not markedly reduce cell viability at concentrations up to 100 μg/mL and improved dexamethasone-induced morphological impairment of myotubes. The extract reduced MAFbx, MMP-2, and MMP-9 expression while restoring phosphorylated p38, MyoD, and myogenin expression, indicating suppression of atrophy- and remodeling-related responses, together with the recovery of myogenic signaling. Among the major identified compounds, all attenuated dexamethasone-induced myotube atrophy and quercetin showed the most pronounced morphological recovery. Molecular docking analysis targeting p38α showed the highest binding affinity for α-tocopherol, followed by quercetin and ascorbic acid, supporting potential interactions between the major compounds and p38 MAPK-related signaling. Conclusions: Collectively, these findings suggest that M. charantia attenuates sarcopenic changes by promoting myogenic differentiation and modulating the p38 MAPK-associated pathways.

This study compared the temporal effects of traditional cigarettes and e-cigarettes on lung health in male Rattus norvegicus over 8- and 12-week periods. Thirty rats were evaluated for tracheal/alveolar histopathology and systemic markers (IL-6, TNF-α, SOD-3, MDA). Chronic cigarette exposure (12 weeks) and nicotine aerosol (8 weeks) significantly suppressed weight gain, while ascorbic acid aerosol caused less growth inhibition. At 8 weeks, cigarette exposure (K3) induced adaptive tracheal mucosal thickening (66.88 ± 17.92 µm vs. 52.40 ± 2.63 µm in control K1), increased goblet cells (4.2 ± 2.44 N/mm), elevated SOD-3 (12.75 ± 1.10 pg/mL), and initiated emphysematous alveolar expansion (469.77 ± 91.31 µm vs. 202.03 ± 29.38 µm in K1 in K1). Conversely, 12-week cigarette smoke (K4) triggered epithelial exhaustion, significantly thinning the tracheal mucosa (34.65 ± 6.55 µm) and elevating systemic IL-6 (11.45 ± 1.17 pg/mL vs. 8.43 ± 0.88 pg/mL in control K2). Notably, chronic electronic ascorbic acid aerosolization (K6) preserved localized alveolar structural layouts and limited septal thickening compared with nicotine groups. However, it failed to suppress systemic inflammation, as evidenced by elevated IL-6 levels. In conclusion, while ascorbic acid aerosols moderate localized parenchymal destruction compared to nicotine, chronic aerosol exposure accelerates systemic immune activation.

BACKGROUND: Environmental noise is a non-specific stressor that can activate stress-response pathways and increase the production of reactive oxygen species, contributing to oxidative stress in the brain. Limbic regions such as the amygdala and hippocampus play key roles in stress processing and are particularly vulnerable to oxidative damage. Acetylsalicylic acid (ASA) has been reported to possess antioxidant and anti-inflammatory properties. Therefore, the present study aimed to determine whether ASA pretreatment provides protective effects against white noise-induced oxidative stress and inflammation, both systemically and in brain tissue. In the study, ALT (Alanine aminotransferase), creatinine, glucose, total protein, HDL (high-density lipoprotein), urea, uric acid, plasma albumin, cholesterol, and cortisol levels were measured from plasma samples. Malondialdehyde (MDA) and ascorbic acid (vitamin C) levels were measured as an antioxidant from brain tissue homogenates of the whole brain, cortex, cerebellum, amygdala, and hippocampus. interleukin 1β (IL-1β), IL-2, IL-6, granulocyte-macrophage colony-stimulating factor (GMCSF), interferon gamma ( IFN-γ), tumor necrosis factor α (TNF-α), IL-4 and IL-10 levels were measured from plasma samples. RESULTS: In the present study, it was found that the MDA level in the amygdala tissue was significantly lower in the animals in ASA + stress group which underwent ASA pretreatment compared to the other groups (p ≤ 0.05). There was no statistically significant difference in MDA levels in the amygdala tissues of the other three groups. A significant decrease was observed in ASA control group. MDA values in cortex tissue compared to stress control group (p ≤ 0.05). There was no significant difference between the groups regarding MDA levels of other brain regions. When whole brain tissue homogenates were examined in the ASA pretreatment groups, a significant decrease was observed in the vitamin C levels of the animals in ASA + stress group compared to the other groups. (p ≤ 0.05).There was no statistically significant change in IL-1β, IL-2, IL-6, GMCSF, IFN-γ, and IL-10 levels. It was observed that TNF-α levels increased in t

Background/Objectives: Propolis is a resinous natural product rich in phenolic acids and flavonoids, recognized in ethnopharmacology for its antioxidant and anti-inflammatory properties. This study aimed to identify the most bioactive Saudi propolis extract using a bioassay-guided strategy and investigate its chemical profile and mechanistic anti-inflammatory potential. Methods: Four propolis extracts (P1-P4) collected from different regions of Saudi Arabia were evaluated for their antioxidant (DPPH and ABTS) and anti-inflammatory (COX-1 and COX-2) activities. The most active extract was profiled using liquid chromatography-mass spectrometry (LC-MS), followed by molecular docking and molecular dynamics simulations. Results: Among all samples, P3 demonstrated the strongest antioxidant activity, with IC50 values of 25.84 ± 0.96 µg/mL (DPPH) and 32.30 ± 1.20 µg/mL (ABTS), comparable to ascorbic acid (27.45 ± 1.42 and 21.22 ± 0.79, respectively). P3 also exhibited potent and selective COX-2 inhibition with an IC50 of 6.19 ± 0.21 µg/mL (relative to celecoxib, IC50 0.681 ± 0.02 as positive control). LC-MS analysis identified 26 secondary metabolites. Computational studies ranked kaempferol as forming the most conformationally stable COX-2 complex among the ligands examined, including the reference inhibitor, on the basis of molecular dynamics descriptors of pose persistence and conformational confinement. Conclusions: Saudi propolis P3 is a potent source of bioactive compounds with strong antioxidant and selective COX-2 inhibitory activity. These findings highlight its anti-inflammatory potential and suggest its value as a natural lead for developing safer therapeutics targeting inflammation-related chronic diseases.

Visible light (VL) accounts for approximately 50% of the solar radiation reaching Earth's surface and has emerged as a major contributor to skin photoaging and pigmentation disorders, particularly in individuals with darker Fitzpatrick skin phototypes. Increasing evidence suggests that VL exposure induces oxidative stress, inflammation, and melanogenesis by generating reactive oxygen species. In this study, we investigated the protective effects of a topical antioxidant formulation (AOX Mix) containing 15% ascorbic acid, 0.5% ferulic acid, and 1% tocopherol against VL exposure in ex vivo skin biopsies from donors with Fitzpatrick skin phototypes IV-V. To preserve physiological tissue tension and closely replicate in vivo skin responses, human skin explants were maintained using the TenSkin™ culture system. Samples were pretreated with AOX Mix for 30 min, then exposed to VL for 8 h, and collected on Days 2 and 7 for histological and molecular analyses. Our results demonstrated that prolonged exposure to VL disrupted redox homeostasis and induced structural alterations in skin explants, accompanied by increased markers of oxidative stress and pigmentation. In contrast, pre-treatment with AOX Mix significantly attenuated these effects, preserving tissue architecture and reducing molecular indicators of photodamage. In addition, we observed the co-localization of 4-hydroxynonenal and collagen type I, suggesting that oxidative post-translational modification of collagen may contribute to its loss. These findings suggest that antioxidant-based interventions, such as AOX Mix, may be a promising strategy for protecting dark skin against VL exposure.

Radiation-induced liver disease (RILD) remains a clinically significant complication of radiotherapy for malignant neoplasms of the liver and upper abdomen, restricting achievable therapeutic doses and adversely affecting patient outcomes. Conventional photon-based radiotherapy (X-rays/γ-rays) exposes substantial volumes of healthy liver parenchyma and adjacent organs to ionizing radiation, increasing the risk of hepatocellular damage, inflammation, and progressive fibrosis. Electron irradiation (β-particles) represents a promising alternative owing to its limited tissue penetration (~2-3 cm) and steep dose fall-off, which significantly reduces exit dose and may reduce exit dose and limit exposure of paratumoral healthy tissues compared with photon therapy. However, the molecular mechanisms underlying electron-induced hepatic damage and strategies for its prevention remain insufficiently characterized. This review systematically analyzes the pathogenesis of radiation-induced liver damage, encompassing direct DNA damage, oxidative stress, mitochondrial dysfunction, NF-κB-mediated inflammation, cellular senescence, and TGF-β/Smad-driven fibrosis. The comparative dosimetric and radiobiological advantages of electron irradiation over photon therapy are discussed, with particular attention to intraoperative radiotherapy, FLASH, and very high-energy electron techniques. Current radioprotective strategies are critically evaluated, with emphasis on the limitations of amifostine and the multifunctional radioprotective potential of ascorbic acid, including free radical scavenging, attenuation of lipid peroxidation, stimulation of endogenous antioxidant defense, and direct inhibition of radiation-induced DNA strand breaks. Existing gaps in the evidence base are identified, and recommendations for future experimental and clinical research are proposed.

Honey has been traditionally used for the management of respiratory disorders, including asthma, yet its mechanistic relevance in allergic airway inflammation remains insufficiently clarified. The present study investigated the chemical composition, antioxidant capacity, and anti-inflammatory effects of two Moroccan monofloral honeys, Ziziphus lotus (L.) Lam and Eryngium campestre L., in a rat model of ovalbumin (OVA)-induced allergic asthma, and explored potential molecular interactions of major phenolic constituents with key signaling proteins involved in disease pathophysiology. Physicochemical properties were determined according to standard methods. Total phenolic and flavonoid compounds (TPC and TFC) were quantified using colorimetric assays, while ascorbic acid content was determined by titrimetric analysis. Phenolic profiles were characterized by high-performance liquid chromatography, and antioxidant activity was assessed using radical-scavenging and total antioxidant capacity assays. In vivo effects were evaluated through hematological analysis, immunoglobulin E (IgE) quantification, bronchoalveolar lavage cellularity, and histopathological examination. Both honeys met international quality standards and exhibited distinct phenolic signatures. Eryngium campestre L. honey showed higher phenolic and flavonoid contents and stronger antioxidant activity compared with Ziziphus lotus (L.) Lam honey. OVA sensitization induced a marked leukocyte infiltration and elevated the IgE levels, whereas honey supplementation reduced significantly inflammatory cell counts and IgE concentrations and preserved lung architecture. Molecular docking indicated the favorable interactions of quercetin and kaempferol with spleen tyrosine kinase (SYK), mitogen-activated protein kinase 3 (MAPK3), and signal transducer and activator of transcription 6 (STAT6). These findings suggest that Moroccan monofloral honeys exert antioxidant and immunomodulatory effects and may attenuate allergic airway inflammation through the modulation of the key inflammatory signaling pathways. © 2026. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

Malpighia glabra L. (Acerola), belonging to the family Malpighiaceae, is highly rich in phenolics, flavonoids and ascorbic acid content, which are collectively recognized for their potent antioxidant and anti-inflammatory activities. Since ionizing radiation harm is primarily driven by excessive reactive oxygen species generation and persistent inflammation, this study aimed to explore the radioprotective potential of Malpighia glabra leaf extract (MLE) and identify its bioactive constituents. β-isoarborinol, afzelechin, engeletin, and flavonoid glycosides had been isolated from the ethyl acetate fraction, and their structures were assigned based on NMR/MS data. Histopathological examination revealed that MLE treatment attenuated radiation-induced histopathological alterations in multiple organs of irradiated rats. The anti-inflammatory activity of MLE was elucidated by suppression of the intestinal NF-κB/TNF-α signaling cascade, along with systemic suppression of serum TNF-α (>70%) and CRP (>25%). MLE restored redox homeostasis by normalizing GSH, TBARs and TAC levels, ultimately preserving hepatic and renal functions. Otherwise, MLE exhibited modest protective effects on haematological parameters, accompanied by dose-dependent preservation of body weight. These findings identify MLE as a promising natural radioprotective agent and provide a mechanistic basis for its further development as an adjunct strategy to reduce radiation-induced systemic and tissue alterations in a dose-dependent manner. © 2026 The Author(s). Chemistry & Biodiversity published by Wiley‐VHCA AG.

BACKGROUND AND AIMS: Intestinal fibrosis involves extracellular matrix stiffening. Piezo1, a mechanosensitive ion channel highly expressed in intestinal epithelial cells (IECs), may sense this change. We investigated whether IEC Piezo1 drives fibrosis and explored the underlying mechanobiological mechanism. METHODS: Dextran sulfate sodium (DSS)-induced fibrosis models, inflammatory bowel disease (IBD) patient samples, and IEC-specific Piezo1 knockout (Piezo1ΔIEC) mice were used. RNA-sequencing, Seahorse assays, and stiffness-gradient hydrogels (1-10 kPa) were applied to assess Piezo1 function, oxidative phosphorylation (OXPHOS), reactive oxygen species (ROS), epithelial-mesenchymal transition (EMT) of IECs, and the anti-fibrosis effect of vitamin C. RESULTS: Piezo1 expression was significantly upregulated in IECs from fibrotic regions of both DSS model mice and IBD patients. IEC Piezo1 deficiency alleviated DSS-induced intestinal fibrosis without substantially altering chronic inflammation or fibroblast activation/proliferation. Piezo1 deficiency suppressed the partial EMT phenotype in IECs, as evidenced by preserved E-cadherin and Claudin-1 expression. RNA-sequencing and functional assays revealed enhanced OXPHOS activity in Piezo1-deficient IECs. In vitro, matrix stiffness of 4 kPa (mimicking fibrotic tissue) activated Piezo1, increased intracellular Ca2+ and ROS accumulation, and induced EMT. Knockout of Piezo1 or treatment with vitamin C prevented these stiffness-induced changes. Oral administration of high-dose vitamin C in vivo reduced intestinal fibrosis and suppressed IEC EMT. CONCLUSIONS: Piezo1 plays a critical role in the sensing of pathological extracellular matrix stiffness in intestinal fibrosis, driving an ROS-EMT axis that promotes disease progression. Targeting Piezo1 or its downstream ROS pathway, for instance with vitamin C, represents a potential therapeutic strategy for intestinal fibrosis. © The Author(s) 2026. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other per

A ZnO/CuO@amoxicillin nanocomposite was synthesized via a sol-gel route and characterized as a biphasic wurtzite ZnO-monoclinic CuO system with crystallite sizes of about 10-12 nm and an optical band gap of 3.30-3.36 eV, indicating defect-rich interfaces favorable for redox activity. In antidiabetic assays, the nanocomposite showed strong inhibitory effects on alpha-amylase (IC50 = 21.57 ± 1.68 mg/mL) and alpha-glucosidase (IC50 = 13.95 ± 0.76 mg/mL), with activities comparable to acarbose, while anti-inflammatory tests yielded low IC50 values of 0.22 ± 0.03 mg/mL for egg albumin denaturation and 0.34 ± 0.07 mg/mL for human serum albumin, approaching the performance of diclofenac. Antioxidant performance was outstanding, with total antioxidant capacity of 298.27 ± 4.70 mg ascorbic acid equivalents per gram and ferric reducing antioxidant power of 311.67 ± 2.53 mM Fe2 +/g, both higher than ascorbic acid, alongside efficient hydrogen peroxide scavenging (IC50 = 0.16 ± 0.04 mg/mL) and protection against H2O2/FeCl3-induced hemolysis at an IC50 of 0.007 ± 0.00 mg/mL; together with moderate but significant acetylcholinesterase inhibition (IC50 = 33.16 ± 3.02 mg/mL vs. 21.80 ± 2.74 mg/mL for donepezil), these results support ZnO/CuO@amoxicillin as a multifunctional nano-platform for managing oxidative stress, inflammation, and metabolic disorders. © 2026 The Author(s). Chemistry & Biodiversity published by Wiley‐VHCA AG.

PURPOSE OF REVIEW: Despite strong biological plausibility, empiric high-dose micronutrient supplementation has failed to improve outcomes in critically ill patients. This review synthesizes evidence from the past 18 months and outlines the necessary transition toward biomarker-guided precision nutrition. RECENT FINDINGS: Recent evidence has further challenged routine high-dose micronutrient therapy. High-dose intravenous vitamin C failed to improve outcomes and was associated with potential harm in patients with sepsis, COVID-19, severe burns, and post-cardiac arrest syndrome. In contrast, a 2025 meta-analysis reported reduced short-term mortality and shorter ICU stay with vitamin D supplementation in patients on mechanical ventilation. Thiamine may shorten the duration of shock without affecting mortality. Observational studies suggest that carnitine deficiency is common during critical illness, and both deficiency and excess may be associated with adverse outcomes in critically ill patients. Selenium supplementation continues to show no clinical benefits in multiple sepsis phenotypes and high-risk surgical populations. Novel evidence also links trace element dysregulation to critical illness-acquired weakness, implicating copper-dependent cuproptosis, zinc homeostasis, and iron metabolism in the pathogenesis of muscle dysfunction. Advances in biomarkers (e.g. hepcidin, soluble transferrin receptor, ferritin, and selenoprotein P) are enabling more accurate identification of true deficiency states and targeted replacement strategies. SUMMARY: Current evidence does not support routine high-dose single-micronutrient therapy in critically ill patients and suggests potential harm with pharmacological doses of vitamin C. Clinicians should ensure that daily baseline requirements are met and reserve supplementation only for patients with biomarker-confirmed deficiency or biologically defined high-risk phenotypes. Future research should prioritize precision nutritional approaches based on validated biomarkers and individualized metabolic profiling.

Vitamin C is crucial for normal physiology and function. Severely insufficient levels of vitamin C can disrupt these processes, resulting in scurvy, a condition characterized by compromised collagen production and tissue degradation. The purpose of this report is to present a complex case of a pediatric patient with autism spectrum disorder exhibiting nonspecific oral lesions. Histopathological examination of the lesions revealed granulomatous inflammation, suggesting an initial diagnosis of orofacial granulomatosis, with a recommendation to rule out Crohn's disease. Further investigation confirmed the presence of vitamin C deficiency, with the oral lesions responding positively to vitamin C supplementation, indicating that the oral lesions were a manifestation of scurvy. In the United States, scurvy is rare and usually associated with underlying conditions and restrictive diets; if left untreated, severe complications affecting patients' life expectancy may occur. Understanding the clinical manifestations of vitamin C deficiency is crucial for timely diagnosis and effective management.

Kiwifruit (Actinidia spp.), a medicine-food homologous crop with high botanical diversity, is rich in polyphenols, pectin, ascorbic acid, and phytosterols. These bioactive compounds confer diverse pharmacological activities, including antioxidation, anti-inflammation, metabolic regulation, cardiovascular protection, and antitumor effects. This review summarizes the botanical traits, resource distribution, and phytochemical profiles of Actinidia spp., and outlines key advances in propagation, breeding, and postharvest preservation. Recent genomic, transcriptomic, and metabolomic data are integrated to dissect gene families and regulatory networks underlying fruit quality, stress tolerance, and bioactive compound biosynthesis in A. chinensis. Applications in functional foods and ecological agriculture are discussed, and future directions for sustainable utilization are proposed. This work provides a foundation for germplasm innovation, molecular breeding, and high-value kiwifruit utilization.

Vitamin C (L-ascorbic acid) is an essential micronutrient with established roles in antioxidant defense, epigenetic regulation, collagen synthesis, redox signaling, immune modulation, and cellular stress responses. This narrative review critically evaluates the potential role of vitamin C as a modulator of the hallmarks of aging. Although mechanistic studies suggest that vitamin C influences gene expression, inflammatory regulation, mitochondrial function, and cellular stress adaptation, the available evidence remains heterogeneous and is derived predominantly from in vitro and preclinical models, whereas human data are largely observational with limited interventional confirmation. Accordingly, vitamin C should be regarded as a context-dependent modulator of cellular resilience, with potential relevance under conditions of deficiency, inflammation, or increased oxidative stress rather than as a general anti-aging agent. Future studies integrating biomarkers of biological aging with clinically meaningful healthspan outcomes are needed to determine whether these mechanistic observations translate into measurable benefits during human aging.

AIM: Oxidative stress (OS) contributes to Alzheimer's disease (AD) pathology. Vitamins C and E target OS, but their efficacies are limited by poor intracellular delivery. Encapsulation in nanovesicles (NVs) may improve targeted delivery for AD treatment. METHODS: Forty-five rats were randomly assigned to nine groups (n = 5 per group): normal control, scopolamine control, vitamin C, vitamin E, vitamin C + E, turmeric NVs (TNV), TNV-C, TNV-E, and donepezil. Treatment was administered intraperitoneally (IP) for one week before induction of the AD-like model using daily IP administration of scopolamine and continued for two weeks. During this time, behavioral activities were conducted, and brain tissues were collected for analysis. RESULTS: Vitamins C and E showed encapsulation efficiencies of 12.36 ± 1.01% and 55.24 ± 5.82%, with loading capacities of 14.34 ± 1.37% and 40.70 ± 3.52, respectively. TNV-C and TNV-E increased brain levels of vitamins E and C, enhanced antioxidant defense and cognitive abilities, and reduced acetylcholinesterase activity in dementia rats. TNV-C and TNV-E also protected against neuroinflammation and neuritic plaque formation. Vitamin-loaded TNVs were more effective than free vitamins in improving antioxidant status and cognitive outcomes in AD rats. CONCLUSION: This study highlights the potential of vitamin-loaded NVs as therapeutics for AD. Plain Language Summary: Alzheimer’s disease (AD), which affects memory, thinking and learning, has limited effective drugs for its management. Unfortunately, these therapeutics in most cases offer only palliative measures and do not prevent the disease from advancing from mild to severe stages. On the other hand, therapeutics like antioxidants that target oxidative stress and mitigate disease progression face the challenges of low intracellular delivery to the brain. In this study, we focused on improving the delivery of antioxidant vitamins (C and E) to the brain for effective management of AD. Nanovesicles were isolated from turmeric rhizomes and utilized for the encapsulation of vitamins to produce nanodrugs. It was observed that loading of antioxidant vitamins into these vesicles improved delive