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BACKGROUND: L-cysteine is thought to be a conditionally essential (i.e., essential under certain conditions) amino acid for neonates. It is a precursor of glutathione, an antioxidant that may reduce oxidation injury. The addition of cysteine to parenteral nutrition (PN) allows for the reduction of the amount of methionine in PN, thereby limiting hepatotoxicity, and acidifies the solution, thereby increasing calcium and phosphate solubility, and potentially improving bone mineralization. OBJECTIVES: To determine the effects of supplementing parenteral nutrition with cysteine, cystine or its precursor N-acetylcysteine on neonatal growth and short and long-term outcomes. SEARCH STRATEGY: The standard search method of the Cochrane Neonatal Review Group was used. MEDLINE (1966-December 2005), EMBASE (1974-December 2005), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006) and recent abstracts (until December 2005) from the Society for Pediatric Research/American Pediatric Society, Eastern Society for Pediatric Research, and Society for Parenteral and Enteral Nutrition were searched. SELECTION CRITERIA: All randomized (RCTs) and quasi-randomized trials that examined the effects of cysteine, cystine or N-acetylcysteine supplementation of neonatal PN were reviewed. Predetermined outcome variables included growth, nitrogen retention, mortality, morbidity secondary to oxidation injury, bone accretion, acidosis, liver disease, and cysteine levels. DATA COLLECTION AND ANALYSIS: The standard methods of the Cochrane Collaboration and its Neonatal Review Group were used. Statistical analysis included relative risk, risk difference, and weighted mean difference (WMD). MAIN RESULTS: Six trials fulfilled entry criteria. The majority of patients in these trials were preterm. Five small trials evaluated short-term cysteine supplementation of cysteine-free PN. One large multicenter RCT evaluated short-term N-acetylcysteine supplementation of cysteine-containing PN in extremely low birth weight infants (< or = 1000 grams). PRIMARY OUTCOMES: Growth was not significantly affected by cysteine supplementation (evaluated in one quasi-randomize

INTRODUCTION: This study assessed the changes in functional connectivity from resting functional magnetic resonance imaging (fMRI) in patients with Parkinson's disease (PD) given N-Acetylcysteine (NAC), the prodrug to L-cysteine and a precursor to the natural biological antioxidant glutathione (GSH). The aim of this study was to determine whether NAC is associated with changes in functional connectivity, particularly in the basal ganglia, and improvements in Parkinson's symptoms. METHODS: Forty-four patients with PD were randomized to either weekly intravenous infusions of NAC (50 mg/kg) plus oral doses (500 mg twice per day) for six months plus standard of care, or standard of care only. Participants received pre and post brain imaging with resting Blood Oxygen Level Dependent (BOLD) MRI to measure functional connectivity between key brain regions involved with PD. These findings were compared to changes in PD symptoms as measured by the Unified Parkinson's Disease Rating Scale (UPDRS). RESULTS: There were significant differences in the NAC group compared to the control group in functional connectivity measures after NAC. Specifically, there was significantly different functional connectivity between basal ganglia structures and the precuneus, precentral gyrus, postcentral gyrus, and particularly the Rolandic operculum. Changes in the precuneus also correlated with changes in UPDRS scores. CONCLUSION: The results suggest that NAC may positively affect brain functional connectivity in PD patients, with corresponding positive clinical effects. Larger scale studies are warranted.

BACKGROUND: This study investigates the eradication rate and adverse reaction rate of immune regulator spleen aminopeptide combined with standard quadruple therapy in treating Helicobacter pylori (HP) infection and explores the mechanism of immune regulator in eradicating HP infection. METHODS: A total of 80 patients with confirmed HP infection admitted to The Sixth Hospital of Ningbo and The Second Hospital of Yinzhou District of Ningbo from September 2024 to December 2024 were assigned into the control and observation groups were assigned into the control and observation groups (40 cases per group) according to the random number table method. The control group was treated with pantoprazole, citric acid bismuth potassium, amoxicillin capsules, and furazolidone; the observation group received spleen aminopeptide oral lyophilized powder in addition to the control group's treatment. The duration was 14 days for both groups. Compare the eradication rate, adverse reaction incidence, and changes in immune function between 2 different curative schemes for treatment of HP infection. RESULTS: The eradication rate was significantly higher in the observation group than in controls (intention-to-treat: 95.00% vs 80.00%, odds ratio: 0.211, 95% confidence interval: 0.042-1.063; per-protocol: 97.44% vs 84.21%, odds ratio: 0.140, 95% confidence interval: 0.016-1.228; both P < .05). The incidence of adverse events in the observation group was markedly lower than that in control subjects (7.7% vs 26.3; P < .05). After treatment, the levels of CD4+, CD3+, and CD4+/CD8+ ratio increased in both groups, while the level of CD8+ decreased. The levels of CD4+, CD3+, and CD4+/CD8+ in the observation group were significantly higher and the level of CD8+ was significantly lower than those in controls (both P < .05). CONCLUSION: The combination of spleen aminopeptide and bismuth quadruple therapy has a high eradication rate, fewer adverse events, and better immune function improvement.

STUDY QUESTION: Does the addition of three antioxidants to culture media during gamete collection, insemination, and embryo culture increase the clinical pregnancy rate from fresh blastocyst transfers? SUMMARY ANSWER: The clinical pregnancy rate from fresh blastocyst transfers was not increased by the addition of antioxidants to IVF and embryo culture media. WHAT IS KNOWN ALREADY: Addition of antioxidants to media is beneficial in mouse IVF, embryo culture, and cryopreservation. Prospective clinical trials of sibling human oocytes found an improvement in embryo quality and increased pregnancy rates from frozen blastocyst transfers in older patients. STUDY DESIGN, SIZE, DURATION: Single-centre, prospective randomized controlled trial, superiority study comparing media with or without the addition of antioxidants from January 2019 to November 2021. A total of 1482 patients were randomized before egg collection. Patients and their doctors were blinded to the treatment group. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients undergoing IVF/ICSI cycles and intending to undergo a fresh transfer of a single blastocyst were recruited. Exclusion criteria were previous participation in the study, use of cryopreserved oocytes/embryos, artificial oocyte activation, freeze-all cycle, or extraction of sperm from testicular biopsy. Seven hundred thirty-nine patients were randomized to control media and 743 patients to media containing the 'A3' antioxidant combination of acetyl-L-carnitine, α-lipoic acid, and N-acetyl-L-cysteine (treatment group). MAIN RESULTS AND THE ROLE OF CHANCE: The clinical pregnancy rate per randomized patient per cycle from fresh embryo transfer was not different between the control and antioxidant media (26.1% vs 22.9%; P > 0.05; RR 0.88 (95% CI 0.73-1.05)). In the Per Protocol population, which excludes patients with protocol violations or without a fresh transfer due to freeze-all or no embryo available, there was also no difference in between the control and antioxidant media in clinical pregnancy rate (36.7% vs 33.2%; P > 0.05; RR 0.90 (95% CI 0.76-1.07)) and live birth rate (32.4% vs 29.5%, P > 0.05). In the Intention-to-Treat population, antioxi

BACKGROUND: Subway systems reduce traffic congestion, air pollution, and carbon dioxide emissions in cities but the impacts of subway air pollution on the health of subway users remain obscure. We conducted a randomized controlled trial involving 83 healthy adults, with 80 included in the final analysis, randomly grouped to spend 2 h daily for 5 consecutive days either in an office or on a subway platform. The fine (PM2.5) and thoracic (PM10) particles concentrations, temperature, and humidity were monitored. Measurements of health parameters were assessed, including lung function and levels of fractional exhaled nitric oxide (FeNO), inflammatory and oxidative stress biomarkers, and metabolites in serum. RESULTS: The subway platform exhibited significantly high pollutant levels, with mean PM2.5 and PM10 concentrations of 193.4 ± 39.4 µg/m3 and 311.5 ± 64.3 µg/m3 respectively. After the 5-day subway exposure, significant declines were observed in lung-function index values, including forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC), maximal voluntary ventilation (MVV) and peak expiratory flow rate (PEFR) as well as serum levels of glutathione peroxidase (GPX)-1 (p < 0.05). Conversely, somatosensory symptom scores, FeNO levels, and serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-8 were strongly elevated (p < 0.05). Results indicated increased arsenic and cobalt and decreased selenium in urine after the subway exposure (p < 0.05). Finally, the subway exposure was associated with disruptions in seven metabolic pathways and nine metabolites, particularly the depletion of L-cysteine, pretyrosine and O-acetyl-L-serine. CONCLUSIONS: This study provides the first evidence that repeated exposure to subway airborne particles is associated with reduced lung function and increased respiratory and systemic inflammation in healthy adults. Our results underscore the need to develop strategies to mitigate exposure risks, ultimately protecting public health in urban environments. © 2025. The Author(s).

Growing evidence suggests that the depletion of plasma NAD+ and glutathione (GSH) may play an important role in the development of metabolic disorders. The administration of Combined Metabolic Activators (CMA), consisting of GSH and NAD+ precursors, has been explored as a promising therapeutic strategy to target multiple altered pathways associated with the pathogenesis of the diseases. Although studies have examined the therapeutic effect of CMA that contains N-acetyl-l-cysteine (NAC) as a metabolic activator, a system-wide comparison of the metabolic response to the administration of CMA with NAC and cysteine remains lacking. In this placebo-controlled study, we studied the acute effect of the CMA administration with different metabolic activators, including NAC or cysteine with/without nicotinamide or flush free niacin, and performed longitudinal untargeted-metabolomics profiling of plasma obtained from 70 well-characterized healthy volunteers. The time-series metabolomics data revealed the metabolic pathways affected after the administration of CMAs showed high similarity between CMA containing nicotinamide and NAC or cysteine as metabolic activators. Our analysis also showed that CMA with cysteine is well-tolerated and safe in healthy individuals throughout the study. Last, our study systematically provided insights into a complex and dynamics landscape involved in amino acid, lipid and nicotinamide metabolism, reflecting the metabolic responses to CMA administration containing different metabolic activators. Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.

Conditioning therapy is an essential procedure prior to hematopoietic stem cell transplant (HSCT), imposing a great impact on the outcomes of recipients. We performed a prospective randomized controlled trial to assess the outcome of HSCT recipients with myeloid malignancies after receiving the conditioning therapy consisting of modified BUCY (mBUCY), N-acetyl-L-cysteine (NAC), and decitabine. Enrolled patients were randomly allocated to either Arm A (decitabine, day -12 to -10; NAC, day -9 to +30; mBUCY, day -9 to -2), or Arm B (mBUCY regimen followed by stem cells infusion). Seventy-six patients in Arm A and 78 patients in Arm B were finally evaluated. The results showed platelet recovery accelerate in Arm A, with more patients achieving a platelet count of ≥50 × 109 /L than Arm B at day +30 and +60 (p = .004 and .043, respectively). The cumulative incidence of relapse is 11.8% (95% CI 0.06-0.22) in Arm A, and 24.4% (95% CI 0.16-0.35) in Arm B (p = .048). The estimated 3-year overall survival rate was 86.4% (±4.4%) and 79.9% (±4.7%) in 2 arms, respectively (p = .155). EFS at 3 years was 79.2% (±4.9%) in Arm A and 60.0% (±5.9%) in Arm B (p = .007). Intracellular reactive oxygen species (ROS) level was found to be reversely correlated with platelet recovery, and fewer patients in Arm A displayed excessive ROS within hematopoietic progenitor cells compared to Arm B. In conclusion, the addition of decitabine and NAC to mBUCY is a feasible and promising conditioning therapy for myeloid malignancies patients. © 2023 Wiley Periodicals LLC.

BACKGROUND: Alzheimer's disease (AD) is associated with metabolic abnormalities linked to critical elements of neurodegeneration. We recently administered combined metabolic activators (CMA) to the AD rat model and observed that CMA improves the AD-associated histological parameters in the animals. CMA promotes mitochondrial fatty acid uptake from the cytosol, facilitates fatty acid oxidation in the mitochondria, and alleviates oxidative stress. METHODS: Here, we designed a randomised, double-blinded, placebo-controlled phase-II clinical trial and studied the effect of CMA administration on the global metabolism of AD patients. One-dose CMA included 12.35 g L-serine (61.75%), 1 g nicotinamide riboside (5%), 2.55 g N-acetyl-L-cysteine (12.75%), and 3.73 g L-carnitine tartrate (18.65%). AD patients received one dose of CMA or placebo daily during the first 28 days and twice daily between day 28 and day 84. The primary endpoint was the difference in the cognitive function and daily living activity scores between the placebo and the treatment arms. The secondary aim of this study was to evaluate the safety and tolerability of CMA. A comprehensive plasma metabolome and proteome analysis was also performed to evaluate the efficacy of the CMA in AD patients. RESULTS: We showed a significant decrease of AD Assessment Scale-cognitive subscale (ADAS-Cog) score on day 84 vs day 0 (P = 0.00001, 29% improvement) in the CMA group. Moreover, there was a significant decline (P = 0.0073) in ADAS-Cog scores (improvement of cognitive functions) in the CMA compared to the placebo group in patients with higher ADAS-Cog scores. Improved cognitive functions in AD patients were supported by the relevant alterations in the hippocampal volumes and cortical thickness based on imaging analysis. Moreover, the plasma levels of proteins and metabolites associated with NAD + and glutathione metabolism were significantly improved after CMA treatment. CONCLUSION: Our results indicate that treatment of AD patients with CMA can lead to enhanced cognitive functions and improved clinical parameters associated with phenomics, metabolomics, proteomics and imaging analysis. Trial registration ClinicalT

This investigation aimed to assess the effect of N-acetylcysteine (NAC) as an adjuvant treatment to alleviate visceral leishmaniasis (VL). The present work includes both blinded randomized clinical intervention and experimental in vitro studies. The clinical trial included 60 patients with VL randomly allocated into two groups: a test group (n = 30) treated with meglumine antimoniate plus NAC (SbV + NAC) and a control group (n = 30) treated with meglumine antimoniate only (SbV). The primary outcome was clinical cure (absence of fever, spleen and liver sizes reduction, and hematological improvement) in 180 days. The cure rate did not differ between the groups; both groups had similar results in all readout indices. The immunological parameters of the patients treated with SbV + NAC showed higher sCD40L in sera during treatment, and the levels of sCD40L were negatively correlated with Interleukin-10 (IL-10) serum levels. In addition, data estimation showed a negative correlation between the sCD40L levels and the spleen size in patients with VL. For the in vitro experiments, peripheral blood mononuclear cells (PBMCs) or PBMC-derived macrophages from healthy donors were exposed to soluble Leishmania antigen (SLA) or infected with stationary promastigotes of Leishmania infantum in the presence or absence of NAC. Results revealed that NAC treatment of SLA-stimulated PBMCs reduces the frequency of monocytes producing IL-10 and lowers the frequency of CD4+ and CD8+ T cells expressing (pro-)inflammatory cytokines. Together, these results suggest that NAC treatment may modulate the immune response in patients with VL, thus warranting additional investigations to support its case use as an adjuvant to antimony therapy for VL.

Polyphenolic antioxidants have been suggested to control the generation of acrylamide during thermal reactions. However, their role in protecting against the toxicity of acrylamide and the mechanism of action regarding profile alteration of biomarkers and metabolome remains unclear. A total of 65 adults were randomized into tea polyphenols (TP) and control groups and served with potato chips, which corresponded to an intake level of 12.6 μg/kg·bw of acrylamide, followed by capsules containing 200 mg, 100 mg or 50 mg TP, or equivalent placebo. Moreover, nontargeted urinary metabolomics analysis in acrylamide exposed rats was conducted using ultra-high performance liquid chromatography linked with a quadrupole-orbitrap high-resolution mass spectrometry. Our results showed that supplementation with catechins promoted the excretion of N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-l-cysteine in both humans and rats. We also found that epigallocatechin gallate (EGCG) or epicatechin (EC) intervention attenuated the ratio of hemoglobin adduct of glycidamide to hemoglobin adduct of acrylamide in rat blood. Metabolomics analysis revealed that EGCG/EC intervention regulated the differential expressed metabolites, including l-glutamic acid, 2-oxoglutarate, citric acid, and cysteinylglycine. Kyoto Encyclopedia of Genes and Genomes pathway analysis further showed acrylamide-induced metabolic disorders were improved after EGCG/EC supplementation by glycolipid metabolism (alanine, aspartate and glutamate metabolism, and d-Glutamine and d-glutamate metabolism) and energy metabolism (tricarboxylic acid cycle). Notably, the supplement use of EGCG prevented the cardiometabolic risk after exposure to acrylamide by mediating the phenylalanine and hippuric acid in phenylalanine metabolism. Here we showed the beneficial effect of catechins as major polyphenolic antioxidant ingredients on the toxicity of acrylamide by the changes in biomarkers from metabolic profile analysis based on human and animal studies. These findings shed light into the catechins as natural polyphenolic antioxidants that could be a therapeutic ingredient for preventing acrylamide-induced cardiometabolic toxicity.

Background: Children and adolescents with cancer often undergo aggressive treatment and receive supportive care requiring a long-term tunneled central venous catheter (TCVC). Regular flushing promotes TCVC patency when not in use (i.e., noninfusing). However, TCVC flushing guidelines and the current practice of daily flushing are not based on high-quality evidence. Few studies have compared the effect of less frequent flushing on TCVC patency. The purpose of this study was to evaluate the feasibility of a three times weekly heparin flushing intervention, as compared to daily heparin flushing, in children and adolescents and young adults (AYAs) with noninfusing TCVCs. Methods: Twenty children and AYAs were randomized to one of two groups, standard of care (SOC) (i.e., daily heparin flushing) or intervention (three times weekly heparin flushing) for 8 weeks. Feasibility data (recruitment, retention, acceptability, TCVC patency, and complications) were analyzed descriptively. Results: Twenty of 22 eligible patients were enrolled in the study (90% recruitment rate). Four participants discontinued the study early due to TCVC removal (20% attrition rate). One participant in each group had their TCVC removed due to a central line-associated bloodstream infection, one SOC group participant had their TCVC removed due to damage, and one intervention group participant had their TCVC removed due to discontinuation of treatment. No participants were withdrawn for safety concerns or because they did not find the protocol acceptable. Conclusions: It is feasible to conduct a large-scale randomized controlled trial to investigate a three times weekly heparin flushing intervention in children and AYAs with TCVCs.

Quercetin, a naturally occurring flavonoid, exhibits antiproliferative and pro-apoptotic effects across various cancer models. Topotecan, a topoisomerase I inhibitor, is used in the treatment of retinoblastoma; however, its clinical utility is limited by dose-dependent toxicity. This study aimed to investigate whether quercetin is associated with enhanced topotecan-induced cytotoxicity in retinoblastoma and to explore the underlying mechanisms under both two-dimensional (2D) and three-dimensional (3D) conditions. Cell viability was assessed using the MTT assay, and drug interactions were evaluated using the combination index (CI) based on the Chou-Talalay method. Apoptosis was analyzed by Annexin V-FITC/PI staining and flow cytometry. Reactive oxygen species (ROS) levels and mitochondrial membrane potential were evaluated using fluorometric methods, and N-acetyl-L-cysteine (NAC) was used for functional modulation of oxidative stress. Three-dimensional tumor spheroid models were used to assess treatment effects under conditions that partially recapitulate tumor architecture. Gene expression levels of apoptosis-related markers and PI3K/Akt/mTOR pathway components were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The combination of quercetin and topotecan was associated with synergistic cytotoxic effects in Y79 cells (CI < 1), accompanied by increased ROS levels, mitochondrial membrane depolarization, and elevated apoptotic cell death. NAC co-treatment partially attenuated ROS levels and restored cell viability. In 3D spheroid models, combination treatment induced structural disruption, reduced viability, and increased cell death, effects that were partially reversed by NAC. Gene expression analysis revealed upregulation of pro-apoptotic genes and downregulation of survival-related genes, along with increased PTEN expression. Quercetin is associated with enhanced topotecan-induced cytotoxicity in retinoblastoma cells under both 2D and 3D conditions. These effects were associated with ROS-associated cellular stress, mitochondrial dysfunction, and modulation of apoptotic and survival-related pathways. The partial rescue by NAC supports a co

The emergence of antimicrobial-resistant Salmonella Typhimurium (S. Typhimurium) has compromised clinical treatment and motivated development of alternative therapies. Suppression of bacterial hydrogen sulfide (H2S) production, an established survival mechanism under antibiotic and oxidative stress, offers a promising strategy for antimicrobial therapy. In S. Typhimurium, cysteine desulfhydrase (CDSH) is a key enzyme for H₂S production via L-cysteine degradation. However, the precise role of CDSH in stress tolerance and infection has not been fully defined, nor have inhibitors targeting CDSH been reported. Herein, we showed that genetic deletion of cdsH reduced S. Typhimurium tolerance to hydrogen peroxide (H2O2), potassium permanganate (KMnO4), heat stress, and antibiotics stress. And mechanistic study further revealed that CDSH-derived H2S enhanced the activity of the catalase KatE, which mediated the detoxification of H2O2 by endogenous H2S. Therefore, we extended our efforts to develop CDSH-targeting agents, and identified gallic acid (GA) as a CDSH inhibitor to effectively potentiate the activity of antibiotics in vitro and in vivo. Furthermore, molecular docking indicated that GA interacts with the catalytic pocket of CDSH, suggesting a potential mechanism for its inhibitory effect. Together, these results establish CDSH-mediated H2S production as a key determinant of S. Typhimurium stress tolerance, and GA as a CDSH inhibitor for adjunctive therapies against S. Typhimurium infection.

BACKGROUND: Elicitation is a widely used strategy to enhance secondary metabolite production in medicinal plants. However, the comparative effectiveness of different redox-modulating elicitors and their interactions in regulating antioxidant systems and terpenoid indole alkaloid (TIA) biosynthesis remains insufficiently understood. OBJECTIVES: This study aimed to evaluate and compare the effects of hydrogen peroxide (H) in combination with melatonin (MT) or L-cysteine (Cys) on redox stability, antioxidant defense, phenolic metabolism, and TIA accumulation in Catharanthus roseus in vitro plants. METHODS: In vitro-grown plants were treated with H₂O₂ (H: 20 µM) alone or combined with different concentrations of MT (100, 200 and 400 µM) or Cys (200, 400 and 800 µM). Photosynthetic pigments, antioxidant enzyme activities (CAT, POD, SOD), oxidative stress indicators (H₂O₂, MDA), total phenolic content (TPC) and total flavonoid content (TFC), antioxidant capacity (TAC, FRAP), phenylpropanoid enzymes (PAL, PPO), and major alkaloids (vincristine, vinblastine, ajmalicine) were quantified using spectrophotometric and HPLC analyses. RESULTS: All treatments significantly enhanced antioxidant capacity and secondary metabolite accumulation compared with the control. Cys400 + H treatment was most effective for promoting biomass accumulation, activating antioxidant enzymes and TAC, whereas MT200 + H effectively enhanced TPC and minimized oxidative damage. MT400 + H preferentially improved chlorophyll content, while Cys800 + H strongly promoted carbohydrates accumulation and vincristine production. The highest plant growth, TFC and vinblastine content was recorded under H treatment alone. Ajmalicine content decreased under all elicitation regimes, indicating a redirection of metabolic flux within the TIA pathway. CONCLUSION: The results demonstrate that H in combination with MT or Cys differentially modulates redox balance and metabolic flux, enabling selective enhancement of antioxidant enzymes and valuable alkaloids. Optimized elicitor combinations therefore provide an effective strategy for targeted metabolic engineering of C. roseus under in vitro conditions. © 2026. The Aut

Zoledronic acid (ZOL) is an inhibitor of osteoclast-mediated bone resorption. It is used to treat osteoporosis and skeletal complications in patients with tumor-induced osteolysis. ZOL is also demonstrated to possess anti-cancer activity in several tumors via apoptosis induction. Doxycycline is well-known antibiotic used in treatment of infections caused by bacteria and certain parasites. In this study, we evaluated the possibility if doxycycline could be used as an effective adjuvant to ZOL against osteosarcoma cells. The data showed that co-treatment with doxycycline at non-toxic dose could significantly increase the anti-viability effect of ZOL in osteosarcoma HOS and MG-63 cells in MTT assay and colony formation assay, and largely increased the levels of apoptotic markers, cleaved caspase 3 and PARP, in ZOL-treated cells. Furthermore, as co-treatment with doxycycline, the levels of ROS and autophagy were enhanced in ZOL-treated cells. Administration of N-acetyl-L-cysteine, a reactive oxygen species (ROS) inhibitor, or autophagy inhibitor chloroquine both reduced anti-growth effect of this combined treatment, indicating that the increased ROS and autophagy should be involved in anti-viability effect of combined treatment with ZOL and doxycycline. Taken together, our findings suggested that combined treatment with ZOL and doxycycline may serve as a potential strategy for treating osteosarcoma. © The author(s).

Bladder cancer has a high recurrence rate, which indicates that the therapeutic effects of advanced bladder cancers are still limited. In this study, we combined vorinostat and cyproheptadine as a new treatment for bladder cancer. When combining the two drugs, an additive to synergistic effect is discovered. Furthermore, we modified the structure of vorinostat using cyproheptadine tricyclic ring to get compounds 8 C and O8C, which keep HDAC inhibitory activity and have IC50 lower than 10 μM in 5637, BFTC 905, and MB49 cells. In in vitro assay, vorinostat, 8 C and O8C increased the percentage of cell cycle in G2/M in 5637, while G0/G1 arrest in BFTC 905. Apoptosis was seen in 5637 and slightly in BFTC 905 by the Annexin V-PI staining assay, and a minor rescued cell viability after Z-VAD-FMK pretreatment in 5637. 8 C and O8C slightly decreased MMP, and increased ROS levels. Among different ROS scavenger treatments, only N-acetyl-L-cysteine shows a minor viability rescue, indicating ROS may not take an important role in 8C- and O8C-induced cell death. In the in vivo assay, mice underwent intraperitoneal injection of 8 C, delaying tumor growth compared to cyproheptadine, vorinostat, and O8C individually. Because the water solubility of 8 C is not good, we use its salt form 8C-HCl for further in vivo study. Mice underwent gavage of 8C-HCl, which resulted in delaying tumor growth. In conclusion, 8 C and 8C-HCl, from structure modification of vorinostat by cyproheptadine tricyclic ring, enhance tumor suppressive effect in vitro and in vivo.

l-cysteine ethyl ester (l-CYSee) overcomes adverse effects elicited by systemic injection of morphine on ventilatory parameters and arterial blood-gas chemistry in rats. l-CYSee or l-cysteine, resulting from the deesterification of l-CYSee, may enter enzymatic cascades that produce the ventilatory stimulant molecule, hydrogen sulfide (H2S). dl-propargylglycine (dl-PROP) is an inhibitor of cystathionine-γ-lyase (CSE)-mediated conversion of l-cysteine to H2S and has been widely used in vivo. We examined whether l-CYSee (2 injections × 500 µmol/kg, IV)-induced reversal of the changes in ventilation elicited by morphine (10 mg/kg, IV) in freely moving male Sprague Dawley rats was altered by prior administration of dl-PROP (25 mg/kg, IV). The major findings were 1) the effects of morphine on ventilatory parameters were not affected by subsequent injection of dl-PROP; 2) first injection of l-CYSee elicited a prompt reversal of the adverse effects of morphine that was more pronounced in dl-PROP-treated than vehicle-treated rats; and 3) the actions of the second injection of l-CYSee were dramatically augmented in dl-PROP-treated rats. In addition, the changes in many of the ventilatory parameters during a subsequent hypoxic-hypercapnic (HH) gas challenge were augmented substantially by dl-PROP. This study demonstrates that 1) inhibition of CSE with dl-PROP does not affect the ventilatory actions of morphine, 2) reversal effects of l-CYSee were augmented by blockade of CSE, and 3) blockade of CSE augments the ventilatory responses to HH gas challenge in morphine-treated rats. These unexpected findings suggest that the CSE-dependent production of H2S from l-CYSee countermands l-CYSee reversal of morphine-induced respiratory depression in rats.NEW & NOTEWORTHY The ability of l-cysteine ethyl ester (l-CYSee) to overcome the adverse effects of morphine on breathing is exaggerated by inhibition of cystathionine-γ-lyase (CSE), suggesting that conversion of l-CYSee or l-cysteine to H2S countermands the effects of l-CYSee against morphine.

The PARP inhibitor olaparib is an anti-cancer agent based on synthetic lethality that targets poly (ADP-ribose) polymerases. It is used as a therapeutic agent for breast, ovarian, pancreatic, and prostate cancers carrying BRCA1/2 mutations that cause deficiency in homologous recombination. In recent years, acquired resistance to PARP inhibitors has become a clinical problem in PARP inhibitor-treated patients. Meanwhile, the development of molecular targeted drugs for highly malignant oral cancers has not progressed, and effective treatment strategies are needed. In this study, we identified the histone deacetylase inhibitor NSC-3852 as a compound that synergistically enhances the effects of olaparib in oral squamous cell carcinoma cell lines. N-Acetyl-l-cysteine treatment partially recovered cell survival after co-treatment with olaparib and NSC-3852. Moreover, the combination of olaparib and NSC-3852 rapidly upregulated γH2AX at 2 h after treatment, and induced S-phase arrest and apoptosis at 24 h after treatment, suggesting that this combination induced apoptosis through accumulation of massive DNA damage. Taken together, these findings demonstrate that NSC-3852 is a sensitizer of olaparib and suggest that the combination of NSC-3852 and olaparib may be a useful therapeutic strategy for homologous recombination-proficient cancers, including cancers with acquired resistance to olaparib and high-grade oral squamous cell carcinoma.

Irinotecan (CPT-11), a chemotherapeutic agent used to treat several types of cancer, induces cytotoxic effects on healthy cells. The epidermal growth factor receptor (EGFR) plays a crucial role in various forms of cancer. Nimotuzumab (NmAb), a monoclonal antibody that targets the EGFR, is utilized in some countries to treat malignancies that have an overexpression of EGFR. Yet, there is a lack of literature on the potential anticancer properties of the CPT-11 and NmAb combination on in vitro human cervical cancer cells. This study investigates the apoptosis mode of the CPT-11 and NmAb combination on cervical HeLa cancer cells. The Annexin V/propidium iodide staining examination demonstrated that the combination of CPT-11 and NmAb resulted in a decrease in the number of viable cells and more potent induction of cell apoptosis than the effects of CPT-11 or NmAb alone in HeLa cells. Furthermore, the combined treatment resulted in elevated levels of reactive oxygen species (ROS) and Ca2+ compared to the treatment with CPT-11 or NmAb alone. Cells that were pretreated with N-acetyl-l-cysteine, a substance that scavenges ROS, and then treated with CPT-11, NmAb, or a combination of CPT-11 and NmAb exhibited higher numbers of viable cells compared to those treated with CPT-11 or NmAb alone. The combination of CPT-11 and NmAb resulted in significantly higher caspase-3, -8, and -9 activity levels than CPT-11 or NmAb alone, as measured by flow cytometer assay. The combination of CPT-11 and NmAb in HeLa cells resulted in elevated endoplasmic reticulum stress-, mitochondria-, and caspase-mediated proteins compared to treatment with CPT-11 or NmAb alone. According to these observations, NmAb enhances the effectiveness of CPT-11 in fighting cancer by stimulating cell death in the HeLa cells. Therefore, NmAb has the potential to improve the efficacy of CPT-11 as a future cervical cancer treatment in humans. © 2024 International Union of Biochemistry and Molecular Biology, Inc.

The co-mitogenic effects of the α1-adrenoceptor agonist phenylephrine on S-allyl-L-cysteine (SAC)-induced hepatocyte proliferation were examined in primary cultures of adult rat hepatocytes. The combination of phenylephrine (10-10-10-6 M) and SAC (10-6 M) exhibited a significant dose-dependent increase in the number of hepatocyte nuclei and viable cells compared to SAC alone. This combination also increased the progression of hepatocyte nuclei into the S-phase. The potentiating effect of phenylephrine on SAC-induced cell proliferation was counteracted by prazosin (an α1-adrenergic receptor antagonist) and GF109203X (selective protein kinase C (PKC) inhibitor). In addition, PMA (direct PKC activator) potentiated the proliferative effects of SAC similarly to phenylephrine. In essence, these findings suggest that PKC activity plays a crucial role in enhancing SAC-induced cell proliferation. Moreover, the effects of phenylephrine on SAC-induced Ras activity, Raf phosphorylation, and extracellular signal-regulated kinase 2 (ERK2) phosphorylation were investigated. Phenylephrine (or PMA) in combination with SAC did not augment Ras activity, but further increased ERK2 phosphorylation and its upstream B-Raf phosphorylation. These results indicate that PKC activation, triggered by stimulating adrenergic α1 receptors, further amplifies SAC-induced cell proliferation through enhanced ERK2 phosphorylation via increased B-Raf-specific phosphorylation in primary cultured hepatocytes.

Chemotherapy is an essential strategy for cancer treatment. On the other hand, consistent exposure to chemotherapeutic drugs induces chemo-resistance in cancer cells through a variety of mechanisms. Therefore, it is important to develop a new drug inhibiting chemo-resistance. Although hemistepsin A (HsA) is known to have anti-tumor effects, the molecular mechanisms of HsA-mediated cell death are unclear. Accordingly, this study examined whether HsA could induce apoptosis in aggressive prostate cancer cells, along with its underlying mechanism. Using HsA on two prostate cancer cell lines, PC-3 and LNCaP cells, the cell analysis and in vivo xenograft model were assayed. In this study, HsA induced apoptosis and autophagy in PC-3 cells. HsA-mediated ROS production attenuated HsA-induced apoptosis and autophagy after treatment with N-acetyl-L-cysteine (NAC), a ROS scavenger. Moreover, autophagy inhibition by 3-MA or CQ is involved in accelerating the apoptosis induced by HsA. Furthermore, we showed the anti-tumor effects of HsA in mice, as assessed by the reduced growth of the xenografted tumors. In conclusion, HsA induced apoptosis and ROS generation, which were blocked by protective autophagy signaling.

AIMS: To compare quantitatively the efficacy and tolerability of pharmacologically active interventions in the treatment and prevention of alcohol-induced hangover. METHODS: Systematic review of placebo-controlled randomised trials in healthy adults that evaluated any pharmacologically active intervention in the treatment or prevention of hangover. We searched Medline, Embase, PsycINFO and CENTRAL from database inception until 1 August 2021. The primary efficacy outcome was any continuous measure of overall hangover symptoms and the primary tolerability outcome the number of people dropping out because of adverse events (AEs). Quality was assessed using the Grading of Recommendations Assessment Development and Evaluation (GRADE) framework. RESULTS: A total of 21 studies were included reporting on 386 participants. No two studies reported on the same intervention; as such, meta-analysis could not be undertaken. Methodological concerns and imprecision resulted in all studied efficacy outcomes being rated as very low quality. When compared with placebo, individual studies reported a statistically significant reduction in the mean percentage overall hangover symptom score for clove extract (42.5% vs 19.0%, P < 0.001), tolfenamic acid (84.0% vs 50.0%, P < 0.001), pyritinol (34.1% vs 16.2%, P < 0.01), Hovenia dulcis fruit extract (P = 0.029), L-cysteine (P = 0.043), red ginseng (21.1% vs 14.0%, P < 0.05) and Korean pear juice (41.5% vs 33.3%, P < 0.05). All studied tolerability outcomes were of low or very low quality with no studies reporting any drop-outs because of AEs. CONCLUSIONS: Only very low quality evidence of efficacy is available to recommend any pharmacologically active intervention for the treatment or prevention of alcohol-induced hangover. Of the limited interventions studied, all had favourable tolerability profiles and very low quality evidence suggests clove extract, tolfenamic acid and pyritinol may most warrant further study. © 2021 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

High alcohol intake is an independent risk factor for upper gastrointestinal (GI)-tract cancers. There is increasing evidence that acetaldehyde, the first metabolite of ethanol, might be responsible for ethanol-associated carcinogenesis. Especially among Asian heavy drinkers with the ALDH2-deficiency gene, i.e., a genetic inability to remove acetaldehyde, the risk of digestive tract cancers is markedly increased. Local acetaldehyde production from ethanol either by oral microbes, mucosal cells or salivary glands is a plausible carcinogenic agent in the saliva. The aim of our study was to examine whether is it possible to bind carcinogenic acetaldehyde from saliva with L-cysteine, which is slowly released from a special buccal tablet. Nine healthy male volunteers took part in our study, and each subject served as his own control. A placebo or L-cysteine-containing tablet was fastened under the upper lip. Thereafter the volunteers ingested 0.8 g/kg of body weight of 10% (v/v) ethanol, and saliva samples were collected at 20 min intervals for 320 min. Salivary acetaldehyde and ethanol levels were analysed by headspace gas chromatography. The mean reduction of acetaldehyde concentration of the saliva with the L-cysteine tablet compared to placebo was 59% (CL(95%) 43%, 76%). Area under the curve (AUC(0-320min)) with the L-cysteine and placebo tablet were 54.3 +/- 11 microM x hr and 162 +/- 34.2 microM x hr (mean +/- SEM), respectively (p = 0.003). After alcohol intake, up to two-thirds of carcinogenic acetaldehyde can be removed from saliva with a slow-releasing buccal L-cysteine drug formulation. Thus, a buccal cysteine tablet could potentially be used to prevent upper GI-tract cancers, especially among high-risk individuals. Copyright 2001 Wiley-Liss, Inc.

Otitis media (OM) is a frequent disease with incidence rate of 5300 cases per 100,000 people. Recent studies showed that polymicrobial biofilm formation represents a significant pathogenic mechanism in recurrent and chronic forms of OM. Biofilm enables bacteria to resist antibiotics that would typically be recommended in guidelines, contributing to the ineffectiveness of current antimicrobial strategies. Given the challenges of successfully treating bacterial biofilms, there is an growing interest in identifying novel and effective compounds to overcome antibacterial resistance. The objective of this review was to provide an overview of the novel compounds with antibiofilm effects on bacterial biofilm formed by clinical isolates of OM. The systematic review included studies that evaluated antibiofilm effect of novel natural or synthetic compounds on bacterial biofilm formed from clinical isolates obtained from patients with OM. The eligibility criteria were defined using the PICOS system: (P) Population: all human patients with bacterial OM; (I) Intervention: novel natural or synthetic compound with biofilm effect; (C) Control standard therapeutic antimicrobial agents or untreated biofilms, (O) Outcome: antibiofilm effect (biofilm inhibition, biofilm eradication), (S) Study design. The PRISMA protocol for systematic reviews and meta-analysis was followed. From 3564 potentially eligible studies, 1817 duplicates were removed, and 1705 were excluded according to defined exclusion criteria. A total of 41 studies with available full texts were retrieved by two independent authors. Fifteen articles were selected for inclusion in the systematic review which included 125 patients with OM. A total of 17 different novel compounds were examined, including N-acetyl-L-cysteine (NAC), tea tree oil, xylitol, eugenol, Aloe barbadensis, Zingiber officinale, Curcuma longa, Acacia arabica, antisense peptide nucleic acids, probiotics Streptococcus salivarius and Streptococcus oralis, Sodium 2-mercaptoethanesulfonate (MESNA), bioactive glass, green synthesized copper oxide nanoparticles, radish, silver nanoparticles and acetic acid. Staphylococcus aureus was the most commonly studie

Acrylamide is widely found in a variety of fried foods and cigarettes and is not only neurotoxic and carcinogenic, but also has many potential toxic effects. The current assessment of acrylamide intake through dietary questionnaires is confounded by a variety of factors, which poses limitations to safety assessment. In this review, we focus on the levels of AAMA, the urinary metabolite of acrylamide in humans, and its association with other diseases, and discuss the current research gaps in AAMA and the future needs. We reviewed a total of 25 studies from eight countries. In the general population, urinary AAMA levels were higher in smokers than in non-smokers, and higher in children than in adults; the highest levels of AAMA were found in the population from Spain, compared with the general population from other countries. In addition, AAMA is associated with several diseases, especially cardiovascular system diseases. Therefore, AAMA, as a biomarker of internal human exposure, can reflect acrylamide intake in the short term, which is of great significance for tracing acrylamide-containing foods and setting the allowable intake of acrylamide in foods. © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

At present, central venous access devices (CVADs) are widely used in clinical practice. The reasons for CVAD obstruction caused by precipitated medication or lipids are increasingly complex. However, there is no clear treatment program for CVAD obstruction caused by precipitated medication or lipids. The target of this study was to analyze data regarding obstruction caused by precipitated medication or lipids in CVADs and to calculate the efficacy of different treatment methods. A systematic review with meta-analysis was conducted in alignment with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. The PubMed, Web of Science, EMBASE, Cochrane Library, CINAHL, and China National Knowledge Internet databases were searched for original research published before 2018. There were 1356 publications initially screened, with one additional study identified through snowballing. Seven studies met the inclusion criteria. The reasons for obstruction, except for clot formation, primarily included the following: mechanical complications; lipid deposition; mineral deposition; or drug precipitation. Meta-analysis showed that sodium hydroxide resulted in the highest recanalization rate in lipid deposition, followed by ethanol, and the difference was significant. The efficacy analysis revealed that hydrochloric acid and l-cysteine have similar effects on mineral deposition and drug precipitation. According to this review, the most effective methodology was shown to be the intravenous perfusion of sodium hydroxide in several treatments when the obstruction is caused by lipid deposition. In contrast, mineral deposition and drug deposition are best treated with l-cysteine to recover the patency of central venous access devices.

SETTING: Eliminating tuberculosis in high-burden settings requires improved diagnostic capacity. Important tests such as Xpert® MTB/RIF and culture are often performed at centralised laboratories that are geographically distant from the point of specimen collection. Preserving specimen integrity during transportation, which could affect test performance, is challenging. OBJECTIVE: To conduct a systematic review of commercial products for specimen preservation for a World Health Organization technical consultation. DESIGN: Databases were searched up to January 2018. Methodological quality was assessed using Quality Assessment of Technical Studies, a new technical study quality-appraisal tool, and Quality Assessment of Diagnostic Accuracy Studies-2. Studies were analysed descriptively in terms of the different products, study designs and diagnostic strategies used. RESULTS: Four products were identified from 16 studies: PrimeStore-Molecular-Transport-Medium (PS-MTM), FTA card, GENO•CARD (all for nucleic acid amplification tests [NAATs]) and OMNIgene•SPUTUM (OMS; culture, NAATs). PS-MTM, but not FTA card or GENO•CARD, rendered Mycobacterium tuberculosis non-culturable. OMS reduced Löwenstein-Jensen but not MGIT™ 960™ contamination, led to delayed MGIT time-to-positivity, resulted in Xpert performance similar to cold chain-transported untreated specimens, and obviated the need for N-acetyl-L-cysteine-sodium hydroxide decontamination. Data from paucibacillary specimens were limited. Evidence that a cold chain improves culture was mixed and absent for Xpert. The effect of the product alone could be discerned in only four studies. CONCLUSION: Limited evidence suggests that transport products result in test performance comparable to that seen in cold chain-transported specimens.

The purpose of this systematic review and meta-analysis was to evaluate the diagnostic value of salivary biological markers in the diagnosis of head and neck carcinoma. Studies were gathered by searching Cochrane, EMBASE, LILACS, MEDLINE, and PubMed. The references were also crosschecked and a partial grey literature search was undertaken using Google Scholar. The methodology of selected studies was evaluated using the 14-item Quality Assessment Tool for Diagnostic Accuracy Studies. After a two-step selection process, 15 articles were identified and subjected to qualitative and quantitative analyses. The studies were homogeneous, and all had high methodological quality. Combined biomarkers demonstrated better accuracy with higher sensitivity and specificity than those tested individually. Furthermore, the salivary biomarkers reviewed predicted the early stages of head and neck carcinoma better than the advanced stages. A restricted set of five single biomarkers (interleukin-8, choline, pipecolinic acid, l-phenylalanine, and S-carboxymethyl-l-cysteine) as well as combined biomarkers demonstrated excellent diagnostic test accuracy. The present systematic review confirms the potential value of a selected set of salivary biomarkers as diagnostic tools for head and neck carcinoma.

156. Hepatogastroenterology. 2014 Sep;61(134):1642-8. Pre-medication to improve esophagogastroduodenoscopic visibility: a meta-analysis and systemic review. Chen HW, Hsu HC, Hsieh TY, Yeh MK, Chang WK. BACKGROUND/AIMS: The use of pre-medication to improve visibility in gastrointestinal endoscopy has not been well addressed and remains controversial. The aim is to evaluate the effects of current pre-medication on endoscopic visualization. METHODOLOGY: We made the overall strategies to search the different databases and assessed the quality of included studies according to the included and excluded standard. 1541 patients were treated with pre-medication. RESULT: Ten prospective studies involving 1541 patients were included. There was improved visibility in patients treated with Simethicone (weighted mean difference -4.3; 95% confidence interval (CI), -4.94 to -3.67), compared to those who did not use Simethicone. In the Simethicone based regiment, administration of Pronase was noted with significantly improved visibility in the location of antrum and fundus, compared to those who did not use; however, administration of N-acetyl-L-cysteine could not lead to significantly improved visibility. Simethicone offered better visibility than N-acetyl-L-cysteine and Pronase alone. CONCLUSIONS: There is improved visibility with pre-medication using Simethicone before esophagogastroduodenoscopy. In the Simethicone based regimen, administration of Pronase or N-acetyl-Lcysteine may be of little use in improving visibility. Based on the literature review, Simethicone dissolved in the water with the acceptably lowest ratio of 0.7 can still offer the good visibility but 30 mL of water should be avoided.

Dietary supplements are popular among patients with prostate cancer (PC). The objective of this systematic review was to critically examine double-blind, placebo-controlled randomised clinical trials (RCTs) of non-herbal dietary supplements and vitamins (NHDS) for evidence that prostate specific antigen (PSA) levels were reduced in PC patients. Five databases were searched from their inception through December 2012 to identify studies that met our inclusion criteria. Methodological quality was independently assessed by two reviewers using the Cochrane tool. Eight RCTs met the eligibility criteria and were of high methodological quality. The following supplements were tested: isoflavones (genistein, daidzein, and glycitein), minerals (Se) or vitamins (vitamin D) or a combination of antioxidants, bioflavonoids, carotenoids, lycopenes, minerals (Se, Zn, Cu, and Mg), phytoestrogens, phytosterols, vitamins (B2, B6, B9, B12, C, and E), and other substances (CoQ10 and n-acetyl-l cysteine). Five RCTs reported no significant effects compared with placebo. Two RCTs reported that a combination of antioxidants, isoflavones, lycopenes, minerals, plant oestrogens and vitamins significantly decreased PSA levels compared with placebo. One RCT did not report differences in PSA levels between the groups. In conclusion, the hypothesis that dietary supplements are effective treatments for PC patients is not supported by sound clinical evidence. There are promising data for only two specific remedies, which contained a mixture of ingredients, but even for these supplements, additional high quality evidence is necessary before firm recommendations would be justified.

Selenium is an essential dietary micronutrient, exerting beneficial effects over a limited range of concentrations. Insufficient dietary intake of selenium increases the risk of type 2 diabetes, infertility, immune dysfunction, prostate cancer, cognitive decline, prostate cancer, colorectal cancer in females, skeletal muscle disorders, overall mortality and an endemic cardiomyopathy known as Keshan disease. Excessive intake of selenium is toxic, leading to a condition termed selenosis, that is associated with damage to the nails, dermatitis, alopecia, central nervous system dysfunction and death. Selenium exerts its biological effects through low-molecular weight molecules, through a small family of selenoproteins which contain the 21st amino acid selenocysteine, and via selenium-binding proteins, in which an atom of selenium is covalently bound to a cysteine residue. In addition to being regulated by body selenium status, the abundance and function of these biomolecules can be controlled by other dietary components (including copper, zinc, folic acid, resveratrol, vitamin A and α-linoleic acid) and other factors, such as exercise and caloric restriction. This review comprehensively surveys the effects of selenium-containing biomolecules on aging and aims to generate rationales underpinning the biphasic effects of this element on life-span, health-span and disease. This will provide a framework for understanding the effects of selenium on mechanisms of aging, as the starting point for development of interventions that will promote longevity and health-span.

OBJECTIVE: Selective fetal growth restriction (sFGR) in dichorionic-diamniotic (DCDA) twins is associated with the risk of adverse neurodevelopment; however, the underlying metabolic dysregulation remains poorly characterized. We aimed to characterize the neonatal hair metabolome associated with sFGR in DCDA twins and assess its predictive value for long-term neurodevelopment. METHODS: Forty-two pairs of DCDA twins were stratified into the sFGR-DCDA (twins with birth weight [BW] discordance) and DCDA-C (twins with BW concordance) groups. Neonatal hair metabolites were profiled using gas chromatography-mass spectrometry (GC-MS). Pathway analysis and machine learning were used to identify metabolic signatures predictive of neurodevelopment, w

Female-pattern hair loss is common in obese women with polycystic ovary syndrome (PCOS), recently proposed as polyendocrine metabolic ovarian syndrome (PMOS) and is often associated with hypertriglyceridemia (TG), although the underlying mechanisms remain unclear. This study investigated how metabolic factors and androgens contribute to hair loss in female mice exposed to a high-fat diet (HFD). A controlled, parallel-group study using 8-week-old female C57BL/6 mice fed either an HFD (60% kcal fat) or a standard diet for 16 weeks. Mice were sacrificed at baseline and 4-week intervals for serial evaluation of metabolic, hormonal and skin changes (n = 6/group/time point). Hair loss was quantified from digital photographs using the ImageJ and further supported by histological examination. Circulating metabolic and hormonal profiles were measured. In dorsal skin, oxidative stress (malondialdehyde, MDA) and androgen-related markers-5-alpha-reductase type II (5αR2), dihydrotestosterone (DHT) and androgen receptor (AR)-were evaluated using immunohistochemistry, Western blot and enzyme-linked immunosorbent assay. From Week 12 onward, HFD-fed mice exhibited greater weight gain, pronounced dorsal hair thinning and elevated TG, insulin and free androgen index (FAI) levels. Skin MDA, 5αR2, DHT and AR levels also progressively increased. In the secon

Rapid and successful establishment of seedlings, beginning with the penetration of the emerging radicle into the soil, is essential for survival. In roots, root hairs increase the surface area for the absorption of water and solutes while providing the mechanical anchorage necessary for deeper soil penetration during elongation. However, the role of collet hairs, which are morphologically similar to root hairs but synchronously develop at the hypocotyl-root junction during germination, has not been clearly distinguished from that of true root hairs. Furthermore, their physiological significance under soil conditions remains to be validated. During an investigation of the genetic interaction between two genes involved in both cysteine metabolism and root hair development, an independent mutation causing root hair defects was identified. In addition to exhibiting extremely short or collapsed root hairs compared to the wild-type plants, the mutant lacked nearly all collet hairs at the hypocotyl-root junction and frequently displayed an 'exposed-root' phenotype. We mapped this phenotype to a 5-bp deletion in Shaven 3 (SHV3; AT4G26690). Analysis of the collet hair-defective shv3 mutant revealed that collet hairs provide the primary anchorage required for successful radicle penetration and subsequent seedling survival, a process later reinforced by the development of root hairs. © 2026 The Author(s). Physiologia Plantarum pu

BACKGROUND: Biotinidase is an enzyme recycling endogenous biotin by hydrolyzing ε-N-biotinyl lysine (biocytin) to lysine and biotin. Biotin acts as a coenzyme in various carboxylation reactions. Biotinidase deficiency is rare, with an incidence of 1 per 112,271 individuals. OBJECTIVES: Genetic characterization of a 4-month-old boy born out of a consanguineous marriage presented with cutaneous manifestations, alopecia, developmental delay, hypotonia with absent neck holding, respiratory problems, and biotinidase deficiency. METHODS: Biochemical characterization was performed using tandem mass spectrometry and immunofluorescence enzyme assays. Pathogenic genetic variant was identified by Sanger sequencing of the BTD (biotinidase) gene in a patient and his parents. RESULTS: Biochemical characterization indicated elevated methylmalonylcarnitine/hydroxyisovalerylcarnitine and decreased biotinidase, citrulline, glycine, and ornithine levels, suggesting a profound biotinidase deficiency. Sequencing of BTD gene indicates the presence of a 7-bp deletion and a 3-bp insertion (98-104del7ins3) in a homozygous state, resulting in a change of amino acid from cystine to phenylalanine at the 33rd position, causing a frameshift and premature amino acid termination at the 68th position. CONCLUSIONS: A 7-bp deletion and a 3-bp insertion (98-104del7ins3) homozygous variation in the BTD gene segregating in a homozygous recessive manner in the family, causing truncated, nonfunctional biotinidase deficiency in the proband. This is a recurrent mutation and has the potential to be used as a biomarker for screening patients with biotinidase deficiency.

INTRODUCTION: Postbiotics are potential functional feed additives, but their effects on multiple health parameters in dogs remain largely unexplored. METHODS: This study evaluated postbiotics from Bifidobacterium animalis in adult beagle dogs fed a basal diet supplemented with 0% (CONT), 0.05% (LDP), or 0.1% (HDP) postbiotics for 42 days. RESULTS: No differences were observed in growth performance or routine blood parameters. However, postbiotic supplementation significantly increased serum IgA (LDP and HDP), IgM and IgG (HDP only), and reduced pro-inflammatory cytokines TNF-α and IL-6 (both groups), IL-1β (HDP only), while IL-10 was increased only in LDP. The HDP group showed lower malondialdehyde (MDA); SOD increased in both groups, while GSH-Px and CAT increased significantly only in HDP. Bone formation markers (PINP, OC) increased in HDP. Hair quality improved (smoother cuticle, higher glutamic acid, cysteine, proline) in both groups. Fecal acetic, propionic, and isovaleric acids increased in both groups; valeric acid increased only in HDP. Gut microbiota analysis revealed increased beneficial bacteria (such as Limosilactobacillus, Lactobacillus) and decreased potential pathogens (such as Peptoclostridium, Streptococcus). DISCUSSION: Bifidobacterium animalis derived postbiotics safely enhance immune function, antioxidant status, bone metabolism, and hair quality in adult dogs, likely via gut microbiota modulation.

Dog hair keratin byproducts are extremely resistant to degradation and require appropriate waste management technologies. To enhance the degradability of these byproducts, silo cocomposting with food byproducts was performed for 19 weeks. In this study, the physical-chemical analysis (temperature, pH, electrical conductivity, carbon/nitrogen ratios (C/N), germination index, and mineral nutrients) was combined with spectroscopic technologies (ultraviolet-visible (UV-vis), Fourier transform infrared (FTIR) spectroscopy, and scanning electron microscopy (SEM)) as an advanced tool to effectively monitor the maturity of compost, thereby minimizing excessive consumption of time and products. Furthermore, a partial least-squares regression (PLS-R) model was used to predict the final compost quality. As a result, it can be concluded that the compost produced fulfills the norms of applicability of mature compost in agriculture with a C/N ratio below 20 and a germination index of 100%. These results were confirmed by UV-spectroscopy analysis showing an increase in humification and by FTIR depicting the degradation of disulfide bonds in cysteine present in keratin and the degradation of cellulose, hemicellulose, and lignin in food byproducts. This stud

BACKGROUND: Diffuse hair loss and shedding is often managed with food supplements, yet evidence for ingredient combinations is limited. Our exploratory study evaluated a nutritional supplement (Priorin capsules, Bayer) containing millet extract, pantothenic acid (vitamin B5), L-cystine, and biotin (vitamin B7) in healthy subjects with light diffuse hair loss. METHODS: In this open-label, intra-individual, multicenter study, subjects with non-illness-related, light diffuse hair loss used the product (two capsules/day) for 12 weeks. Endpoints included objective measurements of hair density, hair growth coefficient, and hair loss (phototrichogram), subjective evaluations of hair appearance, beauty and volume (hairdresser-rated), consumer perception and acceptance, and tolerability. RESULTS: In 112 subjects (mean age 32 ± 1 years; 93.8% female), hair density (n = 109) and the proportion of hairs in the anagen phase increased significantly, while the telogen proportion decreased (p < 0.001, week 12 vs. baseline). Hair loss had declined by 59% at week 12 (p < 0.001). Significant improvements in the hairdresser-rated hair quality and appearance parameters (shine, softness/elasticity, strength, smoothness, dryness, vitality, volume) were observed (p < 0.001). From week 2, subjects reported progressive improvement in appearance, growth, and slowing of hair loss. At week 12, 90% of subjects perceived improved hair appearance and growth, 85% reported slowing down of hair loss, and 82% were satisfied with the overall hair improvements with treatment. The supplement was generally well tolerated. CONCLUSIONS: The combination of millet extract, pantothenic acid, L-cystine, and biotin was associated with reduced hair loss, improv

INTRODUCTION: Cathepsin C (CTSC), a lysosomal cysteine protease, acts as a primary activator of several critical immune enzymes. Mutations in CTSC can cause a variety of conditions, primarily Papillon-Lefèvre syndrome (PLS) and Haim-Munk syndrome (HMS), both rare autosomal recessive palmoplantar keratoderma (PPK) diseases. CASE REPORT: We report the case of a 24-year-old female patient. Her past medical history revealed an undiagnosed condition associated with symptoms of thick, dry, and cracked skin. Additionally, she is of Myanmar heritage and has shared a family history of similar symptoms. The patient was referred to a dermatologist for further evaluation and genetic sequencing to confirm the diagnosis. Whole-exome sequencing (WES) revealed two heterozygous compound variants in the CTSC gene. DISCUSSION: The report highlighted the clinical findings relevant to CTSC's genetic standpoint regarding the mutational indications of PLS and HMS. These diseases are allelic and share clinical features of PPK, including early-onset periodontal deterioration and early tooth loss. These diseases are lifelong and management is usually palliative and quality-focused. CONCLUSION: The WES confirmed a likely Haim-Munk syndrome diagnosis from compound heterozygous CTSC variants. This aligns with severe PPK and early tooth loss, underscoring the vital need for genetic counseling and further family testing. For dental practitioners, early identification of patients with suspected Papillon-Lefèvre or Haim-Munk syndrome is essential to enable timely genetic referral, appropriate prosthetic re

Amino acids are extremely important nutrients in the feed for fur-bearing animals, and this study was conducted to evaluate the effects of cystine on the development of hair follicles in Rex rabbits. A total of 224 Rex rabbits at the age of 90 days were randomly divided into 4 groups and fed the diets supplemented with 0 (Control), 0.2%, 0.4%, or 0.6% cystine, and the rabbits were fed for 60 days. The hair follicle density on the dorsal skin and the gene expression and protein phosphorylation levels of components of Wnt signalling pathways were determined. In addition, the dermal papilla cells (DPCs) were isolated from the skin of Rex rabbits and cultured with cystine in vitro to determine the gene expression and protein phosphorylation levels of Wnt signalling pathways. The results showed that addition of cystine in the diets could increase the fur quality (p < 0.05), and the appropriate of cystine in Rex rabbits' diets was 0.2%. In addition, cystine added to the cell culture medium changed the DPCs cycle progression and promoted cell proliferation. Furthermore, cystine could affect the Wnt10b, CTNNB1, and Dickkopf-1 gene expression of Wnt signalling pathways in the skin and DPCs of rabbits (p < 0.05), and decreased the levels of phosphorylated CTNNB1 and GSK-3β of Wnt signalling pathways in the skin and DPCs of rabbits (p < 0.05). Dietary cystine supplemental level could promote the fur quality of Rex rabbits, and the appropriate of cystine in Rex rabbit diets was 0.2%. Furthermore, the molecular mechanism of cystine modulates hair follicle development, probably occurs through activation of Wnt signalling pathways, promotes DPCs proliferation, and increases the hair densit

Protein S-palmitoylation is a pivotal yet poorly integrated research field in dermatology. This reversible post-translational lipid modification primarily occurs on cysteine residues and is principally catalyzed by zinc finger and Asp-His-His-Cys DHHC-domain containing proteins (zDHHCs). The S-palmitoylation/depalmitoylation cycle directly affects protein localization, trafficking, stability, and protein-protein interaction, thereby regulating a variety of signaling pathways, including those mediating inflammation and immune reaction. Accumulating evidence has indicated that S-palmitoylation regulates various skin biological functions, including skin inflammation, skin barrier function, hair growth, and melanin synthesis, and is ultimately implicated in the initiation and development of massive dermatoses, such as alopecia and psoriasis. The recent development of new research tools, coupled with S-palmitoylation's therapeutic potential, makes the timely synthesis of its role in skin pathophysiology both critical and opportune. Here, we summarize recent advances in understanding the mechanistic roles of S-palmitoylation in dermatological conditions and evaluate its potential as a therapeutic target for innovative treatment strategies.

The root apical meristem activity and hence plant growth strictly depend on glutathione homeostasis. Despite compelling evidence for this dependency based on glutathione depletion, the cause for the growth arrest had remained unclear. Meristem control may depend on either the absolute amount of glutathione or its redox potential (EGSH). To unambiguously distinguish those two options, we characterized an allelic series of six Arabidopsis mutants affected in glutamate-cysteine ligase, which catalyses the first step in the biosynthesis of reduced glutathione (GSH). When grown under the same conditions, even mutants with 20% and 50% of wild-type GSH amounts are slightly stunted. The most severely compromised mutants, zir1 and rml1, were crossed with either gr1, which was used to induce a pronounced shift in EGSH, or with bir6, which exhibits slightly increased GSH levels. Based on theoretical considerations, these levels are not expec

Androgenetic alopecia (AGA) is a common disorder characterized by hair thinning and loss, significantly affecting individuals. Despite extensive research, the molecular alterations in hair keratin remain unclear owing to the limitations of single-spectrum analytical techniques. Herein, we developed a novel multimolecular spectral characterization method for keratin extracted from the hair samples of patients with AGA (AH-KRT) versus that extracted from the hair samples of healthy individuals (NH-KRT). Through multimolecular infrared imaging and amino acid analysis, key structural differences between AH-KRT and NH-KRT were visualized. Results revealed two characteristic peaks at 1192 cm-1 (sulfonyl alanine, SO vibration) and 1043 cm-1 (cysteine sulfonate); changes in the contents of key amino acids such as cysteine, glycine, and alanine; and shifts in the β-sheet-to-α-helix ratio. These findings provide potential biomarkers for evaluating changes in AH-KRT and offer novel insights into the structural differences between AH-KRT and NH-KRT. In conclusion, this study character

14. Stem Cell Res Ther. 2025 Nov 24;16(1):692. doi: 10.1186/s13287-025-04806-4. The human umbilical cord-mesenchymal stem cell secretome regulates hair growth and cycle transition by promoting methylthioadenosine synthesis via the PI3K/AKT/mTOR pathway. Zhang Y(#)(1)(2)(3), Wang X(#)(1)(2)(3), Chen Q(1)(2)(3), Zhao S(1)(2)(3), Bu L(1)(2)(3), Wu S(1)(2)(3), Huang J(1)(2)(3), Xu X(1)(2)(3), Yang X(1)(2)(3), Miao Y(4), Zhang L(5)(6)(7), Zhang M(8)(9)(10). Author information: (1)Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, No. 1023-1063, Shatai South Road, Baiyun District, Guangzhou, 510515, People's Republic of China. (2)NMPA Key Laboratory for Safety Evaluation of Cosmetics, GDMPA Key Laboratory of Key Technologies for Cosmetics Safety and Efficacy Evaluation, Southern Medical University, No. 1023-1063, Shatai South Road, Baiyun District, Guangzhou, 510515, People's Republic of China. (3)Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, No. 1023-1063, Shatai South Road, Baiyun District, Guangzhou, 510515, People's Republic of China. (4)Department of Plastic and Aesthetic Surgery, Nanfang Hospital of Southern Medical University Guangzhou, No. 1838, North Guangzhou Avenue, Baiyun District, Guangzhou, 510515, Guangdong Province, People's Republic of China. [email protected]. (5)Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, No. 1023-1063, Shatai South Road, Baiyun District, Guangzhou, 510515, People's Republic of China. [email protected]. (6)NMPA Key Laboratory for Safety Evaluation of Cosmetics, GDMPA Key Laboratory of Key Technologies for Cosmetics Safety and Efficacy Evaluation, Southern Medical University, No. 1023-1063, Shatai South Road, Baiyun District, Guangzhou, 510515, People's Republic of China. [email protected]. (7)Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, No. 1023-1063, Shatai South Road, Baiyun District, Guangzhou, 510515, People's Republic of China. [email protected]

Nitrogen-fixing bacteria establish symbiotic relationships with their host plants via two different entry systems: root hair-mediated (intracellular) entry and intercellular entry. However, the molecular mechanisms underlying the intercellular entry system have received relatively little research attention. In this study, we compared the transcriptomes of the nodules and roots of Myrica rubra, which forms an ancient type of symbiosis with Frankia via intercellular entry. We found that cysteine-rich receptor-like secreted protein 1 (CRRSP1) was highly upregulated in M. rubra nodules. We then investigated the function of MrCRRSP1 in Aeschynomene indica, which establishes symbiosis with Bradyrhizobium sp. ORS285 through an intercellular entry system. The overexpression of MrCRRSP1 and AiCRRSP1 in A. indica enhanced the nodule number and plant growth. Exogenous application of glutathione S-transferase (GST)-tagged MrCRRSP1 and AiCRRSP1 in A. indica promoted rhizobial attachment at cracks in the lateral root base, as well