비타민B7 (비오틴)

OBJECTIVE: Previous research has demonstrated an association between vitamin D deficiency and the risk of developing optic neuritis (ON) and multiple sclerosis (MS). However, the role of vitamin supplementation as an intervention for ON has not been thoroughly investigated. This systematic review and meta-analysis assesses whether vitamin supplementation improves visual parameters and disease status among ON patients. RESULTS: A systematic literature search within PubMed, Embase, Web of Science, and the Cochrane Central Register of Clinical Trials yielded a total of 2465 peer-reviewed articles, from which 5 studies met inclusion criteria. The effect of MD1003 (high-dose biotin), vitamin A, and vitamin D on retinal nerve fiber layer (RNFL) thickness from pooled results showed a mean change of 0.15 (SMD 0.15, 95 % CI, -0.33 to 0.64, I2 = 61 %, τ² = 0.11, p = 0.08), which was not significant. Meta-analysis of visual acuity due to MD1003 and vitamin A from two studies showed a mean change of 0.01 (SMD 0.01, 95 % CI, -0.34 to 0.35, I2 = 0 %, τ² = 0, p = 0.36). Significant improvements in RNFL thickness due to vitamin A, visual acuity due to vitamins B1, B6, and B12, foveal sensitivity due to vitamins B1, B6, and B12, and the rate of conversion of ON to MS due to vitamin D were observed in individual studies. CONCLUSIONS: Although meta-analysis showed no significant effect of vitamins A, B1, B6, B7, B12, and D on several visual parameters, improvements observed in individual studies point to the essential role of vitamin sufficiency in ON. Due to the limited available evidence, additional high-quality studies are needed to determine the efficacy of vitamin supplementation as a potential therapeutic for ON. LEVEL OF EVIDENCE: N/A.

BACKGROUND: Trace elements and vitamins, named together micronutrients (MNs), are essential for human metabolism. Recent research has shown the importance of MNs in common pathologies, with significant deficiencies impacting the outcome. OBJECTIVE: This guideline aims to provide information for daily clinical nutrition practice regarding assessment of MN status, monitoring, and prescription. It proposes a consensus terminology, since many words are used imprecisely, resulting in confusion. This is particularly true for the words "deficiency", "repletion", "complement", and "supplement". METHODS: The expert group attempted to apply the 2015 standard operating procedures (SOP) for ESPEN which focuses on disease. However, this approach could not be applied due to the multiple diseases requiring clinical nutrition resulting in one text for each MN, rather than for diseases. An extensive search of the literature was conducted in the databases Medline, PubMed, Cochrane, Google Scholar, and CINAHL. The search focused on physiological data, historical evidence (published before PubMed release in 1996), and observational and/or randomized trials. For each MN, the main functions, optimal analytical methods, impact of inflammation, potential toxicity, and provision during enteral or parenteral nutrition were addressed. The SOP wording was applied for strength of recommendations. RESULTS: There was a limited number of interventional trials, preventing meta-analysis and leading to a low level of evidence. The recommendations underwent a consensus process, which resulted in a percentage of agreement (%): strong consensus required of >90% of votes. Altogether the guideline proposes sets of recommendations for 26 MNs, resulting in 170 single recommendations. Critical MNs were identified with deficiencies being present in numerous acute and chronic diseases. Monitoring and management strategies are proposed. CONCLUSION: This guideline should enable addressing suboptimal and deficient status of a bundle of MNs in at-risk diseases. In particular, it offers practical advice on MN provision and monitoring during nutritional support.

BACKGROUND: Multiple sclerosis (MS) is a common demyelinating disease of the central nervous system. Although the exact pathogenesis remains unknown, the leading theory is that it results from immune system dysregulation. Approved disease-modifying therapy appears to modulate the immune system to improve MS-related outcomes. There is substantial interest in the ability of dietary interventions to influence MS-related outcomes. This is an update of the Cochrane Review 'Dietary interventions for multiple sclerosis' (Farinotti 2003; Farinotti 2007; Farinotti 2012). OBJECTIVES: To assess the effects of dietary interventions (including dietary plans with recommendations for specific whole foods, macronutrients, and natural health products) compared to placebo or another intervention on health outcomes (including MS-related outcomes and serious adverse events) in people with MS. SEARCH METHODS: On 30 May 2019, we searched CENTRAL, MEDLINE, Embase, and Web of Science. We also searched ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform (ICTRP), and Networked Digital Library of Theses and Dissertations (NDLTD). We checked reference lists in identified trials and requested information from trial authors to identify any additional published or unpublished data. SELECTION CRITERIA: We included any randomized controlled trial (RCT) or controlled clinical trial (CCT) examining the effect of a dietary intervention versus placebo or another intervention among participants with MS on MS-related outcomes, including relapses, disability progression, and magnetic resonance imaging (MRI) measures. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Planned primary outcomes were number of participants experiencing relapse and change in disability progression, according to a validated disability scale at the last reported follow-up. Secondary outcomes included MRI activity, safety, and patient-reported outcomes. We entered and analysed data in Review Manager 5. MAIN RESULTS: We found 41 full-text articles examining 30 trials following full-text review. Participants were adults with MS, defined by est

WHAT IS KNOWN AND OBJECTIVE: Chromium is an essential mineral for carbohydrate and lipid metabolism. Results of previous systematic reviews and meta-analyses of chromium supplementation and metabolic profiles in diabetes have been inconsistent. Recently, several published trials have emerged. We conducted a systematic review and meta-analysis to assess the effects on metabolic profiles and safety of chromium supplementation in diabetes mellitus. METHODS: Clinical trials were identified through MEDLINE, the Cochrane library, CINAHL, Web of Science, Scopus and www.clinicaltrial.gov up to May 2013. Historical search of reference lists of related articles was also conducted. Studies were included if they (i) were randomized controlled trials comparing chromium mono- or combined supplementation against placebo, (ii) reported HbA1c or fasting plasma glucose and (iii) were of at least 3 weeks when reporting fasting plasma glucose, or of at least 8 weeks if HbA1c was reported. No language restriction was imposed. Treatment effect and adverse events were estimated with mean difference and odds ratio, respectively. RESULTS AND DISCUSSION: Twenty-five randomized controlled trials met the inclusion criteria. Of these, 22 studies evaluated chromium monosupplementation. One study evaluated chromium yeast combined with vitamins C and E, and two others evaluated chromium picolinate plus biotin (CPB). Overall, chromium mono- and combined supplementation significantly improved glycaemic control (mean difference for HbA1c -0·55%; 95% CI -0·88 to -0·22%; P = 0·001, mean difference for FPG -1·15 mm; 95% CI -1·84 to -0·47 mm; P = 0·001). In particular, chromium monotherapy significantly reduced triglycerides and increased HDL-C levels. The effects on glucose and triglycerides levels were shown especially with chromium picolinate. Glycaemic control may improve with chromium monosupplementation of more than 200 μg daily. HbA1c and FPG also improved in patients with inadequate glycaemic control at baseline. The risk of adverse events did not differ between chromium and placebo. WHAT IS NEW AND CONCLUSIONS: The available evidence suggests favourable effects of chromium supplementation on

A meta-analysis of the effect of biotin on production outcomes of dairy cattle was conducted following a literature review. A total of 11 studies from 9 papers, with information on the milk production and composition data from a total number of 238 cows were extracted and analyzed using meta-analysis software in Stata. Estimated size of effect of biotin was calculated for dry matter intake (DMI), milk production, and composition. Heterogeneity was not significant for all of the parameters (the highest I(2)=12%). Therefore, fixed effects models were used for analysis. With the addition of biotin to lactating dairy cattle, DMI and milk production increased by 0.87 and 1.66 kg/d. No significant effect on percentage of milk fat and milk protein was observed. Additionally, Begg's test indicated no evidence of substantial publication bias for all variables. The influence analysis shows that the removal of any study did not change the direction or significance of the point estimates. It can be concluded that the use of biotin supplements increases DMI and milk yield in lactating dairy cows.

Objectives of this study were to critically review randomized controlled trials, evaluate the effectiveness of supplementation with biotin on milk yield and composition and hoof health in lactating dairy cows, explore sources of heterogeneity among studies, and evaluate publication bias. Quantitative assessments can increase the statistical power with which we study the effect of treatments, such as biotin, on outcomes. A total of 9 papers, with 6 production and 3 hoof health studies, met the eligibility criteria for meta-analysis. Eight studies evaluated various hoof lesions in biotin-supplemented cows that did not meet the inclusion criteria. Eleven comparisons were made of milk production responses to biotin treatment. Data extracted included the number of cows in control and treatment groups, measures of variance of responses (standard error or standard deviation) and P-values. Other data obtained included the duration of treatment before and after calving, parity, breed of cow, type and dose of biotin, delivery method of supplementation, and types of diets. Biotin increased milk production by 1.29 kg per head per day (95% confidence interval=0.35 to 2.18 kg) with no evidence of heterogeneity (I(2)=0.0%). Treatment did not affect milk fat or protein percentages, and a trend to increase fat and protein yields was observed. Milk production and composition results were not influenced by duration of treatment before calving, parity, or diet type. Assessment of biotin supplementation on hoof health indicated that more studies had improved rather than negative or neutral outcomes. The effect of biotin treatment on milk production was relatively large and the effects on fat and protein yields, although not significant, were consistent in direction and magnitude with the milk response. The hoof health responses to biotin should encourage further studies to more effectively define the nature of these responses using consistent criteria for examination of hoof conditions and lameness.

PURPOSE: Athletes are at increased risk for functional constipation due to high-intensity training, irregular diets, and disrupted circadian rhythms. Soluble fibers, particularly konjac glucomannan (KGM), have shown potential in alleviating constipation, but clinical evidence, especially in athletes, is limited. This study aimed to assess the effects of an 8-week KGM intervention on gastrointestinal symptoms and gut microbiota in elite male Taekwondo athletes with functional constipation. METHODS: In this double-blind randomized controlled trial, we enrolled male elite Taekwondo athletes diagnosed with functional constipation according to Rome IV criteria. Participants were randomly assigned to receive either KGM supplementation (dietary intervention group, DG) or placebo (control group, CG) for 8 weeks. Primary outcomes included the Patient Assessment of Constipation Symptoms (PAC-SYM), Patient Assessment of Constipation Quality of Life (PAC-QoL), bowel movement frequency (BMF), Bristol Stool Scale, and the Bowel Function Index (BFI). Stool samples were collected for 16S rRNA gene sequencing to evaluate microbial composition and diversity. RESULTS: Compared to the placebo group, the KGM group exhibited significant improvements in PAC-SYM, PAC-QoL, BMF, and BFI scores (p < 0.05 for all). Microbial analysis revealed a marked increase in α-diversity and elevated relative abundances of Prevotella_9, Phascolarctobacterium, Lactobacillus, Bacteroides, and members of the Prevotellaceae family, alongside reduced levels of Alistipes and Desulfovibrio. Correlation analyses indicated a strong association between microbial shifts and symptom improvement. Functional predictions further suggested differential expression in microbial metabolic pathways, including upregulation of biotin biosynthesis I and nitrate reduction VI (assimilatory), and downregulation of L-methionine biosynthesis III (all p < 0.05). CONCLUSIONS: Konjac glucomannan significantly ameliorated gastrointestinal symptoms in elite athletes with functional constipation, potentially via modulation of the gut microbiota. © 2025. Springer-Verlag GmbH Germany, part of Springer Nature.

Chronic inflammation and gut barrier breakdown contribute to the progression of metabolic syndrome and affect the development of cardiometabolic diseases, especially in persons consuming low-quality diets with limited bioactive compounds. Almonds are a rich source of bioactive compounds with antioxidant and anti-inflammatory properties. We hypothesize almond consumption can help disrupt metabolic syndrome progression by improving gut and cardiometabolic health and decreasing inflammation and oxidative stress. To test this hypothesis, adults with metabolic syndrome were randomized to consume either almonds (2 oz, whole, dry roasted, n = 38) or crackers (control, equal caloric content, n = 39), as a daily snack for 12 weeks, and samples were collected (0, 4, and 12 weeks). Compared with participants consuming crackers, almond consumption resulted in lower plasma total and low-density lipoprotein-cholesterol concentrations, a modest improvement in waist circumference (week 4), and improved dietary intakes of α-tocopherol, soluble fiber, copper, biotin, magnesium, polyunsaturated fatty acids, and monounsaturated fatty acids. Almond consumption raised plasma α-tocopherol concentrations (relative to cholesterol concentrations) and increased excretion of a vitamin E biomarker (α-CEHC). Almond consumption improved biomarkers of gut barrier function and intestinal inflammation (fecal calprotectin, myeloperoxidase) in participants with elevated inflammation at baseline. Total body weight, caloric intake, and markers of carbohydrate metabolism (glucose, insulin), systemic inflammation (plasma interleukin-6, C-reactive protein, lipopolysaccharide-binding protein, CD14), and oxidative damage (malondialdehyde) were not altered by almond consumption. In conclusion, daily almond snacking improves nutrient intake and decreases gut inflammation in participants with metabolic syndrome. These beneficial dietary and inflammatory changes may contribute to the improvements in cardiovascular health observed.

BACKGROUND: 2-Iminobiotin (2-IB) is a biotin analog with neuroprotective properties. It selectively inhibits neuronal and inducible nitric oxide synthase. The primary objective of this study was to assess the safety, tolerability, and pharmacokinetics of 2-IB in patients with ischemic stroke due to large-vessel occlusion treated with endovascular thrombectomy. The secondary objective was to investigate preliminary efficacy. METHODS: In this single-center, randomized, placebo-controlled phase 2a study, patients received continuous infusion of 2-IB or placebo for 24 hours. The primary outcome was safety and tolerability measured by vital parameters and pharmacokinetic parameters in the first 28 hours after treatment and serious adverse events up until 7 days. Secondary and additional outcomes included National Institutes of Health Stroke Scale score and infarct volume at 24 to 48 hours, mortality at 90 days, and (baseline-prognosis adjusted) modified Rankin Scale score at 90 days. RESULTS: In the modified intention-to-treat population, 40 patients were randomized, 20 per treatment group. Median age was 76 (interquartile range [IQR], 66-82) years and 40% were female. Baseline characteristics were similar between groups. Vital parameters during treatment did not differ between groups. In total, 17 serious adverse events occurred, 6 (30%) in 2-IB and 11 (55%) in placebo. Median 2-IB exposure (AUCavg_4 h) was 320 (IQR, 243-395) ng h/mL. Median National Institutes of Health Stroke Scale score at 7 days was 3 (IQR, 1-11) in 2-IB and 3 (IQR, 0-16) in placebo. Median infarct volume at 24 to 48 hours was 12.5 (IQR, 8.4-60.5) mL versus 13.7 (IQR, 4.0-94.5) mL. Median modified Rankin Scale at 3 months was 3 (IQR, 1-3) in the 2-IB group versus 3 (2-6) in placebo-treated patients. Mortality was 15% (3/20) in 2-IB versus 40% (8/20) in placebo. CONCLUSIONS: In patients with ischemic stroke with large-vessel occlusion treated with endovascular thrombectomy, 2-IB is safe and well tolerated. Pharmacokinetic parameters could be predicted well. The efficacy of 2-IB needs to be investigated further in a phase 2b/3 clinical trial. REGISTRATION: URL: www.onderzoekmetmensen.nl; Unique id

80. An Bras Dermatol. 2024 Jul-Aug;99(4):581-584. doi: 10.1016/j.abd.2023.07.008. Epub 2024 Apr 30. Efficacy of 5% topical minoxidil versus 5 mg oral biotin versus topical minoxidil and oral biotin on hair growth in men: randomized, crossover, clinical trial. Valentim FO(1), Miola AC(1), Miot HA(1), Schmitt JV(2). Author information: (1)Department of Infectology, Dermatology, Imaging Diagnosis and Radiotherapy, Faculty of Medicine, Universidade Estadual Paulista, Botucatu, SP, Brazil. (2)Department of Infectology, Dermatology, Imaging Diagnosis and Radiotherapy, Faculty of Medicine, Universidade Estadual Paulista, Botucatu, SP, Brazil. Electronic address: [email protected]. DOI: 10.1016/j.abd.2023.07.008 PMCID: PMC11221127 PMID: 38688776 [Indexed for MEDLINE]

Our study aims to investigate the impact of probiotic consumption during pregnancy on gut microbiota functional diversity in healthy pregnant women. Thirty-two pregnant women were randomly assigned to two groups. The probiotic group (PG) consisted of pregnant women who consumed triple viable Bifidobacterium longum, Lactobacillus delbrueckii bulgaricus, and Streptococcus thermophilus tablets from the 32nd week of pregnancy until delivery. The functional profiles of the gut microbiota were predicted through high-throughput 16S rRNA sequencing results using PICRUSt software and referencing the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. In the gut microbiota of the PG, the genera Blautia and Ruminococcus, as well as the species Subdoligranulum, showed significantly higher relative abundances compared to the control group (CG) (P < 0.05). At Level 1 of the KEGG signaling pathways, there was a significant reduction in the functional genes of the gut microbiota involved in Organismal Systems in the PG (P < 0.05). In Level 2 of the KEGG signaling pathways, there was a significant reduction in the functional genes of the gut microbiota involved in Infectious Disease in the PG (P < 0.05). In Level 3 of the KEGG signaling pathways, the PG exhibited a significant increase in the functional genes of the gut microbiota involved in ABC transporters, Oxidative phosphorylation, Folate biosynthesis, and Biotin metabolism (P < 0.05). The CG showed a significant increase in the functional genes related to Cysteine and methionine metabolism, Vitamin B6 metabolism, Tuberculosis, and Vibrio cholerae pathogenic cycle (P < 0.05). In conclusion, our findings suggest that probiotic supplementation during pregnancy has a significant impact on functional metabolism in healthy pregnant women. IMPORTANCE: Probiotics are considered beneficial to human health. There is limited understanding of how probiotic consumption during pregnancy affects the functional diversity of the gut microbiota. The aim of our study is to investigate the impact of probiotic consumption during pregnancy on the functional diversity of the gut microbiota. Our findings suggest that probiotic supplementatio

The enzyme transglutaminase 2 (TG2) plays a key role in celiac disease (CeD) pathogenesis. Active TG2 is located mainly extracellularly in the lamina propria but also in the villous enterocytes of the duodenum. The TG2 inhibitor ZED1227 is a promising drug candidate for treating CeD and is designed to block the TG2-catalyzed deamidation and crosslinking of gliadin peptides. Our aim was to study the accumulation of ZED1227 after oral administration of the drug. We studied duodenal biopsies derived from a phase 2a clinical drug trial using an antibody that detects ZED1227 when bound to the catalytic center of TG2. Human epithelial organoids were studied in vitro for the effect of ZED1227 on the activity of TG2 using the 5-biotin-pentylamine assay. The ZED1227-TG2 complex was found mainly in the villous enterocytes in post-treatment biopsies. The signal of ZED1227-TG2 was strongest in the luminal epithelial brush border, while the intensity of the signal in the lamina propria was only ~20% of that in the villous enterocytes. No signal specific to ZED1227 could be detected in pretreatment biopsies or in biopsies from patients randomized to the placebo treatment arm. ZED1227-TG2 staining co-localized with total TG2 and native and deamidated gliadin peptides on the enterocyte luminal surface. Inhibition of TG2 activity by ZED1227 was demonstrated in epithelial organoids. Our findings suggest that active TG2 is present at the luminal side of the villous epithelium and that inhibition of TG2 activity by ZED1227 occurs already there before gliadin peptides enter the lamina propria.

BACKGROUND: The prevalence of addiction is increasing in the world. Methadone Maintenance Treatment (MMT) can be associated with severe stress and mild to moderate depressive symptoms. Vitamins and minerals are commonly found in multivitamins seem to improve mood. Therefore, the aim of this study was to evaluate the effect of multivitamins on anxiety and depression in patients undergoing MMT in a double-blind randomized controlled trial. METHODS: The study was designed as a double-blind, randomized controlled trial and involved 70 male MMT patients over the age of 18. Participants were randomized to one of two groups, either those receiving multivitamins or those receiving a placebo for 12 weeks. The multivitamin capsule included vitamin E, B1, B2, B3, B5, B6, B12, C, biotin, folic acid, and zinc. Anxiety and depression were measured using standard questionnaires, before and after the intervention. RESULTS: The between-group comparison (i.e., intervention vs. placebo) indicated there was no significant difference in anxiety scores; however, there was a significant between-group difference in depression scores, favoring the intervention group. CONCLUSIONS: Multivitamin supplementation improved depression but did not have a significant impact on anxiety in patients undergoing MMT.

Combination therapy with biotin and dexpanthenol is a well-known practice in preventing and treating hair loss, however, it is not well studied. In this study, we compared the efficacy of the 6-week treatment with two brands of biotin and dexpanthenol for the treatment of diffuse hair loss. Fifty eligible patients with diffused pattern hair loss, (41 women and 9 men) were randomized in a 1:1 ratio to receive either 6 weekly injections of dexpanthenol ampoule 250 mg/2 ml and biotin ampoule 5 mg/1 ml, manufactured by Pars Behvarzan or Bayer Company. Combing test, Standard scalp photography and trichoscan assessment were performed before the first treatment session and one and 8 weeks after the last one. Patients' satisfaction and drug adverse reactions were also recorded. One and eight weeks after the last treatment session, hair fall count and total hair density significantly improved in both groups (p-value <0.01 for hair fall count and 0.04 and 0.02, for hair density in Pars and Bayer groups, respectively). There was no significant difference between the two groups in any other trichoscan parameter, except for improvement in terminal/vellus hair ratio in the Bayer group in both follow up visits, compared to the Pars group (p-value = 0.02 and 0.033 for weeks one and eight). Six-week treatment with both brands of biotin and dexpanthenol was effective and safe in people with diffused pattern hair loss. © 2022 Wiley Periodicals LLC.

INTRODUCTION: We assessed the efficacy and safety of OPF-105, a novel all-in-one peripheral parenteral nutrition (PPN) solution containing multivitamins by the U.S. Food and Drug Administration in 2000 (FDA2000 recommendation). METHODS: We conducted a phase III trial administering OPF-105 or BFL (combination of a commercially available PPN solution and fat emulsion) to patients after gastrointestinal (GI) tract surgery from postoperative day (POD) 1 up to POD14. Until POD7, nutrients were provided only with OPF-105 or BFL. After blood sampling on POD8, oral food intake was permitted. PPN was administered according to the amount of food intake. RESULTS: Efficacy endpoints were assessed in 99 subjects (OPF group: 52; BFL group: 47). The levels of blood proteins and fatty acids in the two groups were similar on POD8. The transition of these mean levels was similar in both groups from POD1 or 2 to POD9 to 15. The mean preoperative blood vitamin levels were within reference intervals (RIs). On POD1 (before administration), the mean levels of most blood vitamins decreased compared to those of the preoperative levels. In the BFL group, the mean blood levels of vitamin B2, B6, pantothenic acid (PA), folic acid (FA), biotin, and C decreased below or near the lower limit of RIs on POD8, and the mean blood levels of vitamin B6 and C remained low from POD9 to 15. In the OPF group, the mean blood levels of vitamins, excluding vitamin K, were within RIs on POD8 and POD9 to 15. The mean levels of blood vitamin K increased over the upper limit of RIs on POD8 but within RIs from POD9 to 15. There was no obvious difference in the incidence of adverse events between the two groups, which is common after GI tract surgeries. CONCLUSION: Blood vitamin levels decreased when patients were administered PPN without vitamin supplementation during the first week after surgery. The novel PPN formula containing multivitamins recommended by FDA2000 can be safely administered to postoperative patients to maintain blood vitamin levels. © 2022 The Author(s). Published by S. Karger AG, Basel.

PURPOSE: The aim of the present study was to determine whether caffeine concentrations in human lens epithelial cells (LECs) achieved from acute peroral caffeine intake inhibit ultraviolet radiation-induced apoptosis in vitro. METHODS: Patients were planned for cataract surgery of both eyes with a caffeine abstinence of 2 weeks in total, starting 1 week before surgery of the first eye. The second eye was scheduled 1 week after the first eye. At the day of the second eye surgery, patients were given coffee containing 180 mg caffeine shortly before surgery. Lens capsules including LEC, harvested after capsulorhexis, were transferred to a cell culture dish and immediately exposed to close to threshold ultraviolet radiation (UVR). At 24 hr after UVR exposure, apoptotic LECs were analysed by TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining. RESULTS: TUNEL-positive cells were detected in UVR-exposed lens capsules both after caffeine intake and in controls. The mean difference in TUNEL-positive cells between caffeine intake and contralateral controls (no caffeine) resulted in a 95% CI 15.3 ± 10.4% (degrees of freedom: 16). CONCLUSION: Peroral caffeine consumption significantly decreased UVR-induced apoptosis in LEC supporting epidemiological findings that caffeine delays the onset of cataract. © 2020 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Myocardial ischaemia-reperfusion (I/R) injury is a serious illness with high morbidity and mortality. Mounting evidence indicates the utility of sevoflurane (SEV) in the treatment of myocardial I/R injury. This study aimed to explore the molecular mechanisms underlying the protective action of SEV against myocardial I/R injury. A rat model of myocardial I/R injury was established, and I/R rats were treated with different concentrations of SEV. MicroRNA-203 (miR-203) and doublecortin (DCX) expression levels were determined using reverse transcription-quantitative polymerase chain reaction. Putative target relationship between miR-203 and DCX was explored using dual-luciferase reporter gene assay and RNA-binding protein immunoprecipitation assay. Ischaemia-reperfusion rats were treated with SEV, miR-203 antagomir or sh-DCX, followed by determination of oxidative stress- and inflammation-related factor levels using nitrite and enzyme-linked immunosorbent assays, and that of apoptosis-related factors using Western blot analysis. The apoptotic rate of myocardial tissues was determined using TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining, and the infract area was evaluated using triphenyltetrazolium chloride staining. The results showed miR-203 was poorly expressed and DCX was highly expressed in myocardial tissues of I/R rats. Sevoflurane was found to elevate miR-203, and miR-203, in turn, could target and reduce DCX expression. Sevoflurane, miR-203 overexpression or DCX silencing resulted in declined oxidative stress, inflammation, apoptosis and infarct area, ultimately alleviating myocardial I/R injury. Collectively, these findings showed that SEV-activated miR-203 exhibited suppressive effects on myocardial I/R injury in rats and highlighted the SEV/miR-203/DCX axis as a promising therapeutic target for myocardial I/R injury management. © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

In this paper, the self-assembled folate-biotin-quaternized starch nanoparticles (FBqS NPs) were used as carrier system of doxorubicin (DOX) and siRNAIGF1R for the codelivery of both into human lung adenocarcinoma cell lines (A549 cells) in vitro. The cytotoxicity, targeted ligand competition, cell proliferation inhibition, cellular uptake, endocytosis mechanism and target protein suppression of drug-loaded FBqS NPs were evaluated in detail. Compared with several other drug formulations under same condition, siRNAIGF1R/DOX/FBqS NPs exhibited the greatest cytotoxicity to A549 cells and the cytotoxicity was competitively inhibited by free folate in dose-dependent manner. The A549 cells treated by siRNAIGF1R/DOX/FBqS NPs showed the lowest cell proliferation capacity. The energy-dependent clathrin- and caveolae-mediated endocytosis might be the primary cellular uptake mechanism of drug-loaded FBqS NPs. The expression of IGF1R protein in A549 cells treated by siRNAIGF1R/FBqS NPs declined dramatically. So the FBqS NPs were expected as the co-carrier system of chemotherapeutants and siRNAs for future clinical application.

BACKGROUND: Automated immunoassays utilizing the interaction between streptavidin and biotin are widely used. Nonetheless, biotin remains an often overlooked confounder. METHODS: We report the case of a 54-year-old female patient with progressive multiple sclerosis and Hashimoto's thyroiditis who presented herself for a follow-up. Measurements on Roche's cobas® 8000 modular analyzer series suggested severe hyperthyroidism. Initially, no relevant confounders could be identified. RESULTS: All requested thyroid parameters were measured with alternative methods, yielding plausible results. CONCLUSIONS: Biotin is a significant confounder in many immunoassays. Alternative measurement methods or methods of biotin neutralization need to be implemented for certain situations.

Despite advances in cancer therapies, glioblastoma multiforme treatment remains inefficient due to the brain-blood barrier (BBB) inhibitory activity and to the low temozolomide (TMZ) chemotherapeutic selectivity. To improve therapeutic outcomes, in this work we propose two strategies, (i) photodynamic therapy (PDT) as adjuvant treatment and (ii) engineering of multifunctional theranostic/targeted nanoparticles ( m-NPs) that integrate biotin as a targeting moiety with rhodamine-B as a theranostic agent in pluronic P85/F127 copolymers. These smart m-NPs can surmount the BBB and coencapsulate multiple cargoes under optimized conditions. Overall, the present study conducts a rational m-NP design, characterization, and optimizes the formulation conditions. Confocal microscopy studies on T98-G, U87-MG, and U343 glioblastoma cells and on NIH-3T3 normal fibroblast cells show that the m-NPs and the encapsulated drugs are selectively taken up by tumor cells presenting a broad intracellular distribution. The formulations display no toxicity in the absence of light and are not toxic to healthy cells, but they exert a robust synergic action in cancer cells in the case of concomitant PDT/TMZ treatment, especially at low TMZ concentrations and higher light doses, as demonstrated by nonlinear dose-effect curves based on the Chou-Talalay method. The results evidenced different mechanisms of action related to the disjoint cell cycle phases at the optimal PDT/TMZ ratio. This effect favors synergism between the PDT and the chemotherapy with TMZ, enhances the antiproliferative effect, and overcomes cross-resistance mechanisms. These results point out that m-NP-based PDT adjuvant therapy is a promising strategy to improve TMZ-based glioblastoma multiforme treatments.

Inappropriate and disproportionate use of antibiotics is contributing immensely to the development of antibiotic resistance in bacterial species associated with food contamination. The use of natural products in combination can be a potent alternative hurdle strategy to inactivate foodborne pathogens. Here, we explored the pro-oxidant properties of essential oil linalool and vitamin C in combination with copper (LVC) in combating the foodborne pathogens Vibrio fluvialis and Salmonella enterica subsp. enterica serovar Typhi using a three-dimensional (3D) checkerboard microdilution assay. Antibacterial activity in terms of the MIC revealed that the triple combination exerted a synergistic effect compared to the effects of the individual constituents. The bactericidal effect of the triple combination was confirmed by a live/dead staining assay. Reactive oxygen species (ROS) measurements with the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling assay and scanning electron microscopy imaging strongly suggested that the increase in ROS production is the underlying mechanism of the enhanced antibacterial potency of the LVC combination (linalool [1.298 mM], vitamin C [8 mM], copper [16.3 μM]). In addition, the hypersensitivity of oxidative stress regulator mutants (oxyR, katG, ahpC, and sodA mutants) toward LVC corroborated the involvement of ROS in cell death. Live/dead staining and changes in cellular morphology revealed that oxidative stress did not transform the cells into the viable but nonculturable (VBNC) state; rather, killing was associated with intracellular and extracellular oxidative burst. Furthermore, the LVC combination did not display toxicity to human cells, while it effectively reduced the pathogen levels in acidic fruit juices by 3 to 4 log CFU/ml without adversely altering the organoleptic properties. This study opens a new outlook for combinatorial antimicrobial therapy.IMPORTANCE There is a need to develop effective antibacterial therapies for mitigating bacterial pathogens in food systems. We used a 3D checkerboard assay to ascertain a safe synergistic combination of food-grade components: vitamin C, copper, and the esse

para-Aminosalicylic acid (PAS) is a second-line anti-tubercular drug that is used for the treatment of drug-resistant tuberculosis (TB). PAS efficacy in the treatment of TB is limited by its lower potency against Mycobacterium tuberculosis relative to many other drugs in the TB treatment arsenal. It is known that intrinsic metabolites, such as, para-aminobenzoic acid (PABA) and methionine, antagonize PAS and structurally related anti-folate drugs. While the basis for PABA-mediated antagonism of anti-folates is understood, the mechanism for methionine-based antagonism remains undefined. In the present study, we used both targeted and untargeted approaches to identify factors associated with methionine-mediated antagonism of PAS activity. We found that synthesis of folate precursors as well as a putative amino acid transporter, designated MetM, play crucial roles in this process. Disruption of metM by transposon insertion resulted in a ≥30-fold decrease in uptake of methionine in M. bovis BCG, indicating that metM is the major facilitator of methionine transport. We also discovered that intracellular biotin confers intrinsic PAS resistance in a methionine-independent manner. Collectively, our results demonstrate that methionine-mediated antagonism of anti-folate drugs occurs through sustained production of folate precursors.

Chemotherapy has been the standard for cancer therapy, but the nonspecific cytotoxicity of chemotherapeutic agents and drug resistance of tumor cells has limited its efficacy. However, multidrug combination therapy and targeting therapy have resulted in enhanced anticancer effects and have become increasingly important strategies in clinical applications. In this study, a biotin-/lactobionic acid-modified poly(ethylene glycol)-poly(lactic-co-glycolic acid)-poly(ethylene glycol) (BLPP) copolymer was synthesized, and curcumin- and 5-fluorouracil-loaded nanoparticles (BLPPNPs/C + F) were prepared to enhance the treatment of hepatocellular carcinoma. Blank BLPPNPs were shown to have great biocompatibility via both in vitro and in vivo studies. Good targeting of tumor cells of BLPPNPs was confirmed by flow cytometry, fluorescence microscopy, and biodistribution. The synergistic anticancer effects of BLPPNPs/C + F were demonstrated by cytotoxicity and animal studies, while western blotting was used to further verify the synergistic effect of curcumin and 5-fluorouracil. The dual-targeting and drug-loaded codelivery nanosystem demonstrated higher cellular uptake and stronger cytotoxicity for tumor cells. Therefore, these dual-targeting NPs are a promising codelivery carrier that could be made available for cellular targeting of anticancer drugs to achieve better intracellular delivery and synergistic anticancer efficacy.

The aim of this study was to investigate the effects of rapamycin (rapa) and metformin (met), combined administration on testicular torsion-detorsion (T/D) injury. A total of 108 male rats were divided randomly into six groups (n = 18), control, sham-operated, T/D, T/D + met (100 mg/kg), T/D + rapa (0.25 mg/kg) and T/D + met (100 mg/kg)+rapa (0.25 mg/kg). Except for the control and sham groups, torsion was created by rotating the right testis 720° in a clockwise direction for 1 h. Treatment groups received drug intraperitoneally, 30 min before detorsion. The right testis of 6 animals from each group was excised 4 h after detorsion for the measurement of lipid peroxidation, caspase-3, and antioxidant enzyme activities. Histopathological changes and germ cell apoptosis were determined by measuring mean of seminiferous tubules diameters (MSTD) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) test in rest of animals, 24 h after detorsion. In T/D group tissue malondialdehyde (MDA) level and caspase-3 activity increased and the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) decreased in comparison with the control group after detorsion. Met and rapa separately pre-treatment reduced MDA and caspase-3 levels, normalized antioxidant enzyme activities, reduced germ cell apoptosis and improved the MSTD in comparison with T/D group. However combined administration of met and rapa indicated a significant augmented effect as compared to the individual drug interventions on the reversal of T/D induced oxidative stress, apoptosis, and histologic changes, suggesting a synergistic response. Thus, this study shows that rapa and met combination have significant synergistic effects against oxidative stress and apoptosis and opens up further possibilities for the design of new combinatorial therapies to prevent tissue damage after ischemia-reperfusion (I/R).

The aim of this study was to test whether a combination of plant bioactive lipid compounds (also termed 'essential oils') and biotin (PBLC+B) could decrease the mobilization of body reserves and ketosis incidence in postpartum dairy cows. We compared non-supplemented control (CON) cows with cows receiving monensin (MON) as a controlled-release capsule at d -21, and with cows receiving PBLC+B from day (d) -21 before calving until calving (Phase 1) and further until d 37 after calving (Phase 2), followed by PBLC+B discontinuation from d 38 to d 58 (Phase 3). The PBLC+B cows had higher body weight and higher back fat thickness than CON cows and lesser body weight change than MON and CON cows in Phase 3. Body condition score was not different among groups. Milk protein concentration tended to be higher on the first herd test day in PBLC+B vs. CON cows. Milk fat concentration tended to be highest in PBLC+B cows throughout Phases 2 and 3, with significantly higher values in PBLC+B vs. MON cows on the second herd test day. Yields of energy-corrected milk were higher in PBLC+B vs. CON and MON cows in Phase 2 and higher in PBLC+B and MON cows vs. CON cows in Phase 3. The incidence of subclinical ketosis was 83%, 61% and 50% in CON, PBLC+B and MON cows, respectively, with lower mean β-hydroxybutyrate values in MON than in PBLC+B cows in Phase 1 prepartum. The serum triglyceride concentration was higher in PBLC+B vs. CON cows on d 37. No differences were observed in serum glucose, urea, non-esterified fatty acids, cholesterol and bilirubin concentrations. Aspartate transaminase and γ-glutamyltranspeptidase but not glutamate dehydrogenase activities tended to be highest in MON and lowest in PBLC+B in Phase 2. We conclude that PBLC+B prevent body weight loss after parturition and are associated with similar ketosis incidence and partly higher yields of energy-corrected milk compared to MON supplementation of dairy cows.

Erratum in JAMA. 2017 Nov 21;318(19):1937. doi: 10.1001/jama.2017.16959. IMPORTANCE: Biotinylated antibodies and analogues, with their strong binding to streptavidin, are used in many clinical laboratory tests. Excess biotin in blood due to supplemental biotin ingestion may affect biotin-streptavidin binding, leading to potential clinical misinterpretation. However, the degree of interference remains undefined in healthy adults. OBJECTIVE: To assess performance of specific biotinylated immunoassays after 7 days of ingesting 10 mg/d of biotin, a dose common in over-the-counter supplements for healthy adults. DESIGN, SETTING, AND PARTICIPANTS: Nonrandomized crossover trial involving 6 healthy adults who were treated at an academic medical center research laboratory. EXPOSURE: Administration of 10 mg/d of biotin supplementation for 7 days. MAIN OUTCOMES AND MEASURES: Analyte concentrations were compared with baseline (day 0) measures on the seventh day of biotin treatment and 7 days after treatment had stopped (day 14). The 11 analytes included 9 hormones (ie, thyroid-stimulating hormone, total thyroxine, total triiodothyronine, free thyroxine, free triiodothyronine, parathyroid hormone, prolactin, N-terminal pro-brain natriuretic peptide, 25-hydroxyvitamin D) and 2 nonhormones (prostate-specific antigen and ferritin). A total of 37 immunoassays for the 11 analytes were evaluated on 4 diagnostic systems, including 23 assays that incorporated biotin and streptavidin components and 14 assays that did not include biotin and streptavidin components and served as negative controls. RESULTS: Among the 2 women and 4 men (mean age, 38 years [range, 31-45 years]) who took 10 mg/d of biotin for 7 days, biotin ingestion-associated interference was found in 9 of the 23 (39%) biotinylated assays compared with none of the 14 nonbiotinylated assays (P = .007). Results from 5 of 8 biotinylated (63%) competitive immunoassays tested falsely high and results from 4 out of 15 (27%) biotinylated sandwich immunoassays tested falsely low. CONCLUSIONS AND RELEVANCE: In this preliminary study of 6 healthy adult participants and 11 hormone and nonhormone analytes measured by 37 immunoassay

OBJECTIVE: Cardiomyopathy, a popular diagnosis that always obscures more than it reveals, nevertheless has several characteristic histological features. These prominently include widespread focal myocardial fibrosis and associated hypertrophy of surviving cardiac myocyte. In fact, focal noninflammatory degeneration (not necrosis) has been demonstrated as a feature of many forms of cardiac hypertrophy. We hypothesized that this loss of myocardial cells in dilated cardiomyopathy (DCMP) may result from cell death by apoptosis. METHODS: Endomyocardial biopsy specimens from the right ventricles of six patients who suffered from DCMP were studied, and myocardial specimens from two persons who died in motor vehicle accidents were used as negative controls. For identification of apoptosis, immunohistochemistry with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labeling was performed. In addition, apoptosis was confirmed morphologically by confocal laser scanning microscopy with propidium iodide. RESULTS: Apoptosis, that was represented by an apoptotic index ranging from 19.8 to 25.4%, could be extensively seen in myocytes and also rarely in non-myocytes of interstitium and vascular endothelium. Morphologically, there were a lot of nuclei with clumps of condensed chromatin, suggestive of apoptosis. CONCLUSION: The present study demonstrated that myocyte loss in DCMP might be mainly due to the apoptosis of myocytes and interstitial cells, rather than inflammation or cell necrosis.

BACKGROUND: Vitamin D is increasingly recognized for its neuroprotective, anti-inflammatory, and immunomodulatory roles in mental health. However, its delivery to the central nervous system remains constrained by various factors. OBJECTIVE: This systematic review evaluates strategies for optimizing brain-targeted vitamin D delivery, highlighting molecular, physiological, and technological approaches to enhance its efficacy in mental disorders. METHODS: Following PRISMA guidelines, a comprehensive search across PubMed, Web of Science, Scopus, Embase, and PsycINFO was conducted. Relevant studies were assessed thematically, focusing on BBB transport mechanisms, nanocarriers, structural modifications, and transporter-mediated delivery. RESULTS: Strategies including nanotechnology, biotin-based transporter targeting (e.g., SMVT/SLC5A6), DBP-Megalin/Cubilin-mediated transcytosis, and intranasal administration show promise in enhancing vitamin D brain uptake. Differences between serum and brain vitamin D concentrations, genomic and non-genomic VDR pathways, and psychiatric disorder-specific associations (e.g., depression, schizophrenia, ASD) were also examined. CONCLUSIONS: Although limited by the scarcity of large-scale clinical data, emerging strategies demonstrate significant potential in enhancing brain-targeted vitamin D delivery. These findings lay a foundation for future translational research aimed at precision mental health interventions.

BACKGROUND AND OBJECTIVES: Growing evidence has explored the effects of water-soluble vitamins supplementation on glycemic control and insulin resistance in diabetic patients; however, the results of previous meta-analyses are inconsistent. To address this, we conducted an umbrella review to synthesize the evidence on these effects. METHODS AND STUDY DESIGN: A systematic literature search in Web of science, PubMed, and Cochrane Database of Systematic Reviews was performed from 2012 to November 2022. he quality of the meta-analyses was assessed using AMSTAR-2 and GRADE. RESULTS: Fourteen systematic reviews and meta-analyses met the inclusion criteria, examining the effects of five water-soluble vitamins (B-1, B-3, biotin, B-9, and C) on glycemic control and insulin resistance. The findings suggest that vitamin C supplementation can improve glycemic control in type 2 diabetes, as indicated by reduced FBG and HbA1c, with more significant effects observed for durations longer than 30 days. CONCLUSIONS: Insulin resistance is improved by folic acid supplementations. More well-designed individual randomized controlled trials are needed in the future, as well as meta-analysis of higher quality.

BACKGROUND: Episodic ataxia (EA), characterized by recurrent attacks of cerebellar dysfunction, is the manifestation of a group of rare autosomal dominant inherited disorders. EA1 and EA2 are most frequently encountered, caused by mutations in KCNA1 and CACNA1A. EA3-8 are reported in rare families. Advances in genetic testing have broadened the KCNA1 and CACNA1A phenotypes, and detected EA as an unusual presentation of several other genetic disorders. Additionally, there are various secondary causes of EA and mimicking disorders. Together, these can pose diagnostic challenges for neurologists. METHODS: A systematic literature review was performed in October 2022 for 'episodic ataxia' and 'paroxysmal ataxia', restricted to publications in the last 10 years to focus on recent clinical advances. Clinical, genetic, and treatment characteristics were summarized. RESULTS: EA1 and EA2 phenotypes have further broadened. In particular, EA2 may be accompanied by other paroxysmal disorders of childhood with chronic neuropsychiatric features. New treatments for EA2 include dalfampridine and fampridine, in addition to 4-aminopyridine and acetazolamide. There are recent proposals for EA9-10. EA may also be caused by gene mutations associated with chronic ataxias (SCA-14, SCA-27, SCA-42, AOA2, CAPOS), epilepsy syndromes (KCNA2, SCN2A, PRRT2), GLUT-1, mitochondrial disorders (PDHA1, PDHX, ACO2), metabolic disorders (Maple syrup urine disease, Hartnup disease, type I citrullinemia, thiamine and biotin metabolism defects), and others. Secondary causes of EA are more commonly encountered than primary EA (vascular, inflammatory, toxic-metabolic). EA can be misdiagnosed as migraine, peripheral vestibular disorders, anxiety, and functional symptoms. Primary and secondary EA are frequently treatable which should prompt a search for the cause. DISCUSSION: EA may be overlooked or misdiagnosed for a variety of reasons, including phenotype-genotype variability and clinical overlap between primary and secondary causes. EA is highly treatable, so it is important to consider in the differential diagnosis of paroxysmal disorders. Classical EA1 and EA2 phenotypes prompt single gene test and tr

BACKGROUND: Serum urate (SU) concentrations are associated with increased risk of type 2 diabetes, metabolic syndrome, and gout. Both genetic and lifestyle factors can alter SU. The role of genetics in modifying associations between diet and SU is not well understood. OBJECTIVES: We examined if associations between dietary micronutrient intake and SU are modulated by genetic risk for high SU. METHODS: We utilized the United Kingdom Biobank, with 108,992 participants after exclusions. Micronutrient intake was measured by 24-h recall. Polygenic risk scores (PRSs) were generated to estimate genetic ri

BACKGROUND: Diabetic wounds are a common complication and a debilitating condition of diabetes mellitus, which are characterized by chronic inflammation, persistence, and aggravation. Evidence suggests the beneficial influence of Loganin on diabetic complications and inflammation. However, the effectiveness of Loganin on diabetic wounds remains uninvestigated. METHODS: Network pharmacology was applied to identify the potential targets of Loganin in diabetic wound healing. Employing a streptozotocin (STZ)-induced diabetic mouse model, we conducted evaluations pertaining to the effects of Loganin on wound healing and assessment of macrophage-related phenotypes via ELISA, immunohistochemistry, Western blot and qPCR. In vitro, we used J774A.1 mouse macrophage cell line and induced differentiated Th17 cells for experiments. Molecular docking, biotin-labeled pull-down assays and cellular thermal shift assays were applied to investigate direct mechanisms. RESULTS: Loganin topical application accelerated wound healing in diabetic mice, reduced local inflammation, and inhibited NLRP3 inflammasome activation. The IL-17/NF-κB signaling pathway was suppressed by Loganin, thus inhibiting NLRP3 inflammasome. In particular, Loganin inhibited IL-17 A/F production in Th17 cells and targeted the NF-κB p50 subunit in macrophages, thus blocking its nuclear translocation and pro-inflammatory activation. CONCLUSION: Loganin may be considered as an adjuvant or a new therapeutic agent in the management of chronic non-healing diabetic wounds.

Cardiac fibrosis is a defining pathological feature of diabetic cardiomyopathy (DCM), and excessive activation of cardiac fibroblasts plays a critical role in regulating cardiomyocyte function through paracrine signaling. CCN1 (cellular communication network factor 1), an extracellular matrix protein involved in intercellular communication, has been suggested to influence cardiac remodeling, although its specific impact on cardiomyocytes in DCM has remained unclear. In this study, we found that CCN1 expression was markedly elevated in cardiac tissues from DCM mouse models and in insulin-resistant cell models, with fibroblasts serving as the primary source. Proteomic analysis and co-culture experiments demonstrated that CCN1 suppressed cardiomyocyte macroautophagy/autophagy. To determine its role in vivo, we generated fibroblast-specific ccn1 knockout mice and established a DCM model, demonstrating that ccn1 deletion ameliorated cardiac dysfunction and restored autophagic activity. We further identified ITGAV-ITGB1/integrin αvβ1 as the receptor mediating CCN1 signaling in cardiomyocytes. Molecular dynamics simulations and co-immunoprecipitation experiments confirmed that CCN1 engaged ITGAV-ITGB1/integrin αvβ1 through its cysteine-knot-containing (CT) domain. Mechanistically, this interaction activated the downstream PTK2/FAK-MTOR signaling pathway, leading to inhibition of cardiomyocyte autophagy. Together, these findings reveal a previously unrecognized fibroblast-cardiomyocyte signaling axis in which fibroblast-derived CCN1 drives DCM progression by suppressing autophagy through ITGAV-ITGB1/integrin αvβ1-dependent signaling. This work provides mechanistic insight into the pathogenesis of DCM and identifies CCN1 as a potential therapeutic target for mitigating disease onset and progression.Abbreviations: AAV9: adeno-associated virus serotype 9; ADGRE1/EMR1/F4/80: adhesion G protein-coupled receptor E1; BafA1: bafilomycin A1; BSA: bovine serum albumin; C8: compound 8; CCN1: cellular communication network factor 1; CF: cardiac fibroblast; CSA: cross-sectional area; DCM: diabetic cardiomyopathy; EIF4EBP1: eukaryotic translation initiation factor 4E binding protein

In living organisms, the change in the adenosine 5'-monophosphate (AMP)/adenosine 5'-triphosphate ratio serves as a key signal regulating AMP-activated protein kinase (AMPK) activity, which is an important molecule for the control of cellular energy metabolism and serves a key role in a number of diseases, such as diabetes and myocardial infarction. To explore novel AMPK-interacting proteins and investigate their biological functions, the present study used TurboID proximity labeling in U251 cells stably expressing AMPK-TurboID. Novel AMPK-interacting proteins were explored under both normal and CCCP-treated conditions to investigate their biological functions. Stable cell lines overexpressing AMPK-TurboID were successfully established, and interacting proteins were identified through biotin labeling, silver staining and mass spectrometry analysis. Due to the involvement of AMPK in numerous metabolic pathways and the advantages of TurboID over traditional techniques, including its high temporal resolution, in situ labeling in living cells and its ability to capture weak and transient interactions, a number of proteins interacting with AMPK were identified. Six proteins identified by label-free MS were validated by western blotting, showing that the expression levels of menage a trois-1 and DNAJ heat shock protein family (Hsp40) member A1 (DNAJA1) closely matched the MS data. DNAJA1 was selected for further experimentation. TurboID proximity labeling, affinity purification and LC-MS/MS, western blotting, co-immunoprecipitation (co-IP) and immunofluorescence (IF) techniques demonstrated that AMPK and DNAJA1 not only interact with each other but also synergistically protect cells from apoptosis, perhaps providing a basis for targeted therapeutics (such as treatments for diabetes and myocardial infarction). The present study achieved covalent labeling of endogenous proteins located within nanometer distance of the labeling enzyme by adding a biotin-based substrate. The labeled proteins were then captured and enriched using streptavidin-coated magnetic beads for subsequent identification by MS. These MS results, combined with subsequent validation, led to the identif

PURPOSE: Poor diet quality is a known risk factor for type 2 diabetes and related outcomes, including declines in insulin sensitivity. Biological changes that occur in response to diet may explain this relationship. METHODS: This study was conducted in a cohort of young adults (the MetaAIR study, n = 77, 52% female, 57% Hispanic). High dimensional mediation analyses (HIMA) were performed to identity potential metabolite, protein, and miRNA mediators of the relationship between the Healthy Eating Index-2015 (HEI) and insulin sensitivity (Matsuda Index) over a four year follow up period. Features identified by HIMA and significant after correction for multiple comparisons (q < 0.05) were assessed using causal mediation analyses. The indirect effects and proportion mediated by each feature were calculated independently. RESULTS: Each point increase in HEI was associated with a 0.051 (95% CI:0.004, 0.098) point increase in Matsuda Index. Four potential mediators were identified using HIMA: three metabolites (5Z,8Z,11Z-eicosatrienoic acid, pipecolic acid, and biotin), and one protein (F9). Each of these features exhibited a positive indirect effect and independently mediated between 35 and 43% of the total effect. No miRNAs were selected as potential mediators. CONCLUSION: These findings suggest that specific metabolites and proteins may mediate the association between diet and diabetes-related outcomes such as declines in insulin sensitivity, likely through pathways related to inflammation. F9, biotin, pipecolic acid, and 5Z,8Z,11Z-eicosatrienoic acid may be potential targets for monitoring efforts for diet adherence or disease prevention. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-026-01918-3. © The Author(s) 2026.

INTRODUCTION: Insulin resistance and type 2 diabetes mellitus (T2DM) are serious worldwide health issues linked to dyslipidaemia, oxidative stress, impaired glucose metabolism, and persistent inflammation. Although their clinical significance is still unknown, micronutrients like chromium and biotin are thought to affect insulin signalling, glucose homeostasis, and lipid metabolism. The purpose of this review is to compile the preclinical, clinical, and epidemiological data that is currently available regarding the individual and combined effects of chromium and biotin on metabolic outcomes, insulin sensitivity, and glycaemic control. METHODS: Using databases like PubMed, Scopus, and Google Scholar, a thorough search of narrative literature was carried out. Included were pertinent experimental, clinical, and review studies evaluating the use of chromium and/or biotin supplements in diseases like metabolic syndrome, insulin resistance, and type 2 diabetes. With a focus on study design, dosage, duration, mechanistic pathways, and reported metabolic outcomes, the evidence was qualitatively examined. RESULTS: Preclinical research repeatedly shows that biotin and chromium improve oxidative stress markers, lipid profiles, insulin sensitivity, and glucose tolerance. Increased GLUT-4 translocation, AMPK activation, insulin signalling pathway modulation (IRS-1/PI3K/Akt), and biotin-dependent enzyme regulation are some of the mechanisms that mediate these effects. Particularly in those with poor glycaemic control or micronutrient deficiencies, clinical trials show modest but significant improvements in fasting blood glucose, HbA1c levels, insulin resistance indices, and lipid parameters. Glycaemic control, dyslipidaemia, oxidative stress, and cardiovascular risk markers all seem to improve with combined supplementation. Additionally, epidemiological data point to a negative correlation between dietary chromium consumption and the risk of T2DM. DISCUSSION: The results demonstrate the complementary functions of biotin and chromium in controlling the metabolism of fats and carbohydrates. When taken together, they may provide greater metabolic advantages than when taken separ

OBJECTIVES: Vascular endothelial growth factor A (VEGFA) plays a critical role in the pathogenesis of diabetic macular edema (DME) in patients with type 2 diabetes mellitus (T2DM). Herein, we sought to determine whether palmitoylation modulates the stability and function of VEGFA in the context of DME. METHODS: VEGFA protein levels were measured by western blotting in retinal pigment epithelial (RPE) tissues from mice and in cultured RPE cell lines. Palmitoylation of VEGFA was assessed using acyl‑biotin exchange (ABE) and Click‑iT pulldown assays. Cell proliferation was evaluated with the Cell Counting Kit‑8 (CCK‑8) assay. The interaction between VEGFA and zinc finger DHHC-type containing 19 (ZDHHC19) was examined by co‑immunoprecipitation. Retinal histopathology in DME mice was evaluated by hematoxylin‑eosin (H&E) staining. RESULTS: VEGFA levels were elevated in the RPE of DME mice compared with those of T2DM mice. Pharmacological inhibition of palmitoylation with 2‑bromopalmitate (2‑BP) reduced VEGFA protein expression in cultured cells. ZDHHC19 was identified as the palmitoyltransferase responsible for VEGFA. Wild‑type ZDHHC19 failed to palmitoylate the VEGFA‑C387A mutant, and the catalytically inactive ZDHHC19‑C142S mutant also lacked activity toward VEGFA. Overexpression of wild‑type VEGFA or ZDHHC19 significantly promoted RPE cell proliferation, whereas the VEGFA‑C387A and ZDHHC19‑C142S mutants had no effect. Consistent with these in vitro findings, wild‑type VEGFA or ZDHHC19 overexpression exacerbated DME development in mice, while the corresponding mutants did not significantly affect disease progression. CONCLUSION: ZDHHC19‑mediated palmitoylation of VEGFA contributes to DME pathogenesis and may serve as a potential therapeutic target and biomarker for this disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-026-02023-1. © The Author(s), under exclusive licence to Tehran University of Medical Sciences 2026. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author

E3 ubiquitin ligases include hundreds of members that can regulate the half-life of other proteins but also modulate their cellular localization and functions. While MARCH1 appears to target principally immune cell components, such as MHC class II molecules and the co-stimulatory molecule CD86, the repertory of its targets remains to be fully documented. Here, we adapted a proximity-dependent biotin identification (BioID)-based screening approach in live HEK293 cells. We transfected a fusion protein consisting of mouse MARCH1 linked to YFP at its N-terminus and to the biotin ligase of Aquifex aeolicus at its C-terminus. Upon transient overexpression in the presence of biotin, we could recover biotinylated proteins that are presumably found within 10 nm of MARCH1. CD98 and CD71, two previously described targets of MARCH1, were identified. Of 16 other biotinylated proteins identified by semi-quantitative mass spectrometry, ten were tested directly by flow cytometry to monitor their expression in the presence or absence of transfected MARCH1. SNAT2 was particularly sensitive to the presence of MARCH1 and was found to be ubiquitinated on western blots. Thus, BioID2 is an effective mean of characterizing the interactome of MARCH1, and the identification of SNAT2 suggests a role of this ubiquitin ligase in cellular metabolism. © 2026. Published by The Company of Biologists.

Microbiomes and their host environments form complex, interconnected ecosystems. The microbial species within a microbiome, on the one hand, compete for resources, while on the other hand, they exchange vital metabolites to support their survival. These interactions are influenced by the microbial genetic repertoire, environmental conditions, and availability of nutrients. We developed EcoGS (http://www.github.com/KaletaLab/EcoGS), a metabolic modeling tool designed to predict the ecological interactions between pairs of microbes. Applying EcoGS to the microbiomes of two distinct human cohorts revealed a shift from collaborative to exploitative ecological interactions associated with increased dietary intake of simple sugars (glucose and fructose) in diabetic individuals and those living industrialized lifestyles. On the other hand, the consumption of cobalamin (vitamin B12), phylloquinone (vitamin K1), and biotin (vitamin B7), among other compounds, was associated with increased collaboration in the gut microbiome. We conclude that the abundance of simple sugars as an energy source reduces the necessity for microbes to cooperate, thereby increasing competition and hostility among microbiome members. Moreover, our study proposes multiple compounds, such as urate, deoxyadenosine, deoxyguanosine, and hypoxanthine, for in vitro validation tests as dietary interventions that have the potential to restore the ecological balance within the community. EcoGS serves as a valuable tool for exploring microbiome dynamics and their connections to environmental changes and disease.

BACKGROUND: Diabetic cardiomyopathy, a severe complication of diabetes, is marked by mitochondrial dysfunction, metabolic inflammation, and progressive cardiac impairment. Although STING (stimulator of interferon genes) is well recognized as a central mediator of innate immunity, its noncanonical role in metabolic regulation and mitochondrial dynamics in the diabetic heart remains largely unexplored. METHODS: To elucidate the role of STING in diabetic cardiac remodeling, we used single-cell RNA sequencing, echocardiography, and transmission electron microscopy in both genetic (db/db) and chemically induced (high-fat diet [HFD] plus streptozotocin, HFD/streptozotocin) diabetic mouse models. STING knockout mice and primary neonatal mouse cardiomyocytes were used for mechanistic investigations and functional validation. Mitochondrial respiration and glycolytic flux were assessed using Seahorse extracellular flux analysis. Posttranslational modifications of STING, including S-palmitoylation and S-sulfhydration, were evaluated via acyl-biotin exchange and biotin-switch assays, respectively. ENO1 (enolase 1) enzymatic activity was measured in vitro to assess glycolytic reprogramming. Furthermore, 13C-glucose tracing-based targeted metabolomics was performed to quantify cardiac metabolic flux in db/db mice. Glycolytic metabolites, including lactate and pyruvate, were quantified in cardiac tissues and cultured cardiomyocytes to assess glycolytic activity. RESULTS: Exposure to high-palmitate conditions induced mitochondrial DNA leakage, thereby activating the cGAS (cyclic GMP-AMP synthase)-STING (stimulator of interferon genes) signaling pathway in cardiomyocytes. Mechanistically, STING underwent aberrant translocation to mitochondria, where it interacted with the outer membrane protein TOM (translocase of outer mitochondrial membrane) 40 to impair mitochondrial protein import and disrupt mitochondrial homeostasis. In addition, mitochondrial STING functioned as a scaffold to recruit and activate the glycolytic enzyme ENO1, thereby enhancing its enzymatic activity, accelerating glycolytic flux, and promoting lactate accumulation in diabetic cardiac tissues. Notably, diabe

Phosphatidylinositol-5-phosphate 4-kinases (PI5P4Ks) have emerged as candidate drug targets in cancer, neurological, inflammatory, and infectious diseases. Although their canonical function is to phosphorylate PI(5)P to generate PI(4,5)P2, growing evidence points to additional catalytic-independent roles, but how these functions are organized within protein interaction networks remains unclear. Here, we use proximity-dependent biotin identification (BioID) in HeLa cells to map isoform-resolved interactomes of human PI5P4Kα, PI5P4Kβ, and PI5P4Kγ. This approach captures PI5P4K-proximal proteins in intact cells and reveals interaction networks positioning these kinases within trafficking-associated signaling modules. Importantly, BioID analysis indicates that PI5P4Kγ has the most extensive set of proximal interactors among the three PI5P4Ks, consistent with its comparatively low catalytic activity and a prominent scaffold-like function. Among PI5P4Kγ-enriched partners, we highlight the endosomal cargo adaptor SNX17 as a proximal interactor that links PI5P4Kγ to β1-integrin recycling and to cell migration and invasion. By providing a proximity map for all three PI5P4Ks, this study offers a framework to help define contexts in which targeted protein degradation may offer advantages over catalytic inhibition and provides a resource for future mechanistic studies on these phosphoinositide kinases.

AIMS/HYPOTHESIS: Chromatin remodelling is critical for maintaining pancreatic beta cell identity and function, yet the key regulatory mechanisms remain incompletely defined. This study aimed to investigate the role of the switch/sucrose non-fermentable (SWI/SNF) complex subunit BAF60A in preserving beta cell fate and glucose homeostasis. METHODS: Pdx1-Cre-mediated BAF60A-knockout (BaBKO) and BAF60A-overexpressing (BaBOE) mice, together with tamoxifen-inducible adult beta cell-specific Smarcd1 knockout (BaBKOTM) and Isl1 knockout (Isl1BKOTM) mice, were generated to evaluate the role of BAF60A in vivo. Glucose homeostasis was assessed through glucose tolerance tests, insulin tolerance tests and glucose-stimulated insulin secretion (GSIS) assays. Multiomic analyses, including RNA-seq, ATAC-seq, Cleavage Under Targets and Tagmentation (CUT&Tag) and single-cell RNA-seq, were performed to characterise chromatin accessibility and transcriptional changes. BAF60A-interacting proteins were identified with biotin identification (BioID) and GST pull-down assays. Beta cell lineage tracing was used to assess changes in cell identity. In addition, BAF60A and the dedifferentiation marker ALDH1A3 were examined in pancreatic islets from individuals with and without type 2 diabetes. RESULTS: BaBKO mice exhibited significant glucose intolerance, impaired GSIS and pronounced loss of beta cell identity, accompanied by the acquisition of non-beta endocrine features. Inducible deletion of Smarcd1 in adult beta cells similarly impaired beta cell maturation and promoted dedifferentiation, as confirmed by lineage tracing. BAF60A deficiency reduced enhancer accessibility and downregulated beta cell identity genes. Mechanistically, BAF60A physically interacts with the transcription factor islet-1 (ISL1) to regulate transcription of target genes. Adult beta cell-specific Isl1 deletion recapitulated key features of BAF60A deficiency and abolished the beneficial effect of BAF60A overexpression on insulin secretion. Conversely, BaBOE mice exhibited improved glucose tolerance and enhanced GSIS under high-fat diet conditions. Adeno-associated virus-mediated BAF60A overexpression markedly reduced

Gβ5 is a member of the Gβ family; however, unlike other heterotrimeric Gβ proteins, which transduce extracellular signals in response to G-protein coupled receptor (GPCR) activation, Gβ5 negatively regulates GPCR signaling by stabilizing the GTPase-activating proteins (GAP) R7 subfamily of Regulator of G-protein Signaling (R7-RGS) proteins. Mutations in Gβ5 have been implicated in a multisystem developmental disorder. While the regulation of GPCR signaling at the plasma membrane is likely important in this process, Gβ5/R7-RGS also localizes to the cytosol and nucleus. Potential protein-protein interactions of Gβ5 in these subcellular compartments are not well studied, so we sought to characterize the interactome of Gβ5 utilizing a live-cell biotin proximity-labeling assay in Neuro-2a cells coupled with mass spectrometry to identify novel protein interactions of the complex. We identified 48 potential interactors of Gβ5 with two analysis methods, most of which are previously unreported interactions important in neuronal development and function. The enriched phenotypes associated with the Gβ5 interactome in our results align with previously reported phenotypes of Gβ5 deficiencies. Not subject to U.S. Copyright. Published 2026 by American Chemical Society.

BACKGROUND: The Naturally Nutrient Rich (NNR) score is a validated nutrient-density metric that quantifies micronutrient adequacy relative to energy intake, yet its association with type 2 diabetes mellitus (T2DM) risk remains uninvestigated. This study aimed to examine the association between the NNR score and T2DM risk among Saudi adults. METHODS: A hospital-based case-control study was conducted at Prince Abdulaziz bin Musaed Hospital, Saudi Arabia between November 2024 and August 2025, enrolling 140 confirmed T2DM cases and 280 non-diabetic controls (same healthcare facility) matched 1:2 by age and sex. Dietary intake was assessed using a validated 152-item semi-quantitative food frequency questionnaire. The NNR score was calculated as the mean percentage daily value (%DV) of 14 key nutrients per 2,000 kcal (protein, vitamins A, C, D, E, B1, B2, and B12, calcium, zinc, iron, folate, potassium, and unsaturated fatty acids). Logistic regression models were applied to evaluate the association between the NNR score and T2DM risk, with progressive adjustment for age, sex, smoking, physical activity, BMI, and total caloric intake. RESULTS: Cases had significantly higher BMI (28.32 ± 2.64 vs. 26.85 ± 2.15 kg/m2; p = 0.039), caloric intake, carbohydrate, and cholesterol consumption, alongside significantly lower intakes of dietary fibre, PUFA, magnesium, selenium, folate, vitamins A, E, and B₁, beta-carotene, and biotin compared to controls. Participants with higher NNR scores demonstrated significantly greater intakes of fibre, zinc, potassium, magnesium, and multiple B vitamins, without significant differences in total energy or macronutrient intake. Across all logistic regression models, higher NNR scores were independently and inversely associated with T2DM risk, with the fully adjusted model yielding an odds ratio of 0.90 (95% CI: 0.82-0.93; p < 0.001). CONCLUSION: Higher dietary nutrient density, as measured by the NNR score, is significantly and independently associated with reduced odds of T2DM in Saudi adults. These findings underscore the relevance of micronutrient adequacy, beyond total energy intake, in relation to lower odds of T2DM and support the inte

The glycated hemoglobin ratio (HbA1c %) serves as the gold standard for diabetes diagnosis, but traditional detection methods require invasive blood testing. Although saliva holds promising noninvasive potential, the complex salivary matrix and the low abundance of salivary hemoglobin (Hb) and glycated hemoglobin (HbA1c) restrict the development of reliable immunoassays. Here, we present an HbA1c/Hb dual-detection lateral flow assay (LFA) platform for rapid and noninvasive quantification of salivary HbA1c %. The assay integrates two distinct capture strategies onto a single LFA strip: a streptavidin (SA)-biotin bridging system for HbA1c (T1 line) and a conventional double-antibody sandwich format for nonglycated Hb (T2 line). Consequently, our platform enables simultaneous and single-step measurement for the absolute concentrations of both Hb and HbA1c, facilitating the precise calculation of the HbA1c %. The analytical accuracy was validated against paired venous blood samples. Additionally, coupling with a low-cost, 3D-printed, and smartphone-based fluorescence reader, the system provides an economical and efficient point-of care testing solution, particularly for clinical preliminary screening and at-home self-testing. © 2026 American Chemical Society.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a major risk factor for pulmonary tuberculosis (PTB), exacerbates disease severity and reduces the efficacy of anti-tuberculosis therapy. Previous studies have shown that T2DM is associated with exacerbated metabolic disturbances in patients with PTB. However, metabolic differences between PTB patients with comorbid T2DM (PTB-DM) and those with PTB after anti-TB therapy remain unclear. METHODS: Untargeted metabolomic analysis was conducted on plasma samples collected from April 2024 to November 2025 at Tianjin Haihe Hospital, China. A total of 75 participants were enrolled, including healthy controls, patients with newly diagnosed drug-sensitive PTB, patients with PTB-DM, as well as two independent post-treatment groups sampled after 6 months of standard anti-TB therapy: patients with PTB and patients with PTB-DM. RESULTS: Patients with PTB exhibited marked metabolic disturbances, particularly in tyrosine metabolism and steroid hormone biosynthesis. Patients with PTB-DM showed broader metabolic reprogramming, including changes in arginine and proline metabolism, steroid hormone biosynthesis, cAMP signaling, and taurine and hypotaurine metabolism. After 6 months of standard therapy, the PTB_6M group showed treatment-associated metabolic differences, especially in bile acid metabolism, suggesting partial normalization of several metabolic features. In contrast, patients with PTB-DM after treatment showed persistent metabolic abnormalities involving sphingolipid, purine and biotin metabolism. Notably, 12-HETE and 12-HHTrE showed elevated levels in active PTB, decreased levels after treatment, but remained relatively higher in PTB-DM after treatment. CONCLUSIONS: This study offers an integrated assessment of metabolic alterations in PTB and PTB-DM, suggesting that comorbid T2DM is associated with broader metabolic dysregulation during active PTB and persistent post-treatment metabolic abnormalities.

BACKGROUND: Biotin has gained commercial popularity for its claimed benefits on healthy hair and nail growth. Despite its reputation, there is limited research to support the utility of biotin in healthy individuals. OBJECTIVE: To systematically review the literature on biotin efficacy in hair and nail growth. METHODS: We conducted a PubMed search of all case reports and randomized clinical trials (RCTs) using the following terms: (biotin and hair); (biotin and supplementation and hair); (biotin supplementation); (biotin and alopecia); (biotin and nails); (biotin and dermatology), and (biotin recommendations). RESULTS: We found 18 reported cases of biotin use for hair and nail changes. In all cases, patients receiving biotin supplementation had an underlying pathology for poor hair or nail growth. All cases showed evidence of clinical improvement after receiving biotin. CONCLUSIONS: Though its use as a hair and nail growth supplement is prevalent, research demonstrating the efficacy of biotin is limited. In cases of acquired and inherited causes of biotin deficiency as well as pathologies, such as brittle nail syndrome or uncombable hair, biotin supplementation may be of benefit. However, we propose these cases are uncommon and that there is lack of sufficient evidence for supplementation in healthy individuals.