This study aimed at investigating the diversity of endophytic fungi from Coptis chinensis and their activity against methicillin-resistant Staphylococcus aureus (MRSA). Seventy-nine fungal isolates obtained from C. chinensis were identified to belong to 27 species based on morphological features and internal transcript spacer (ITS) gene sequencing analysis. Comparing relative frequency values, the most frequent genera were Colletotrichum and Fusarium, while most frequent species were C. gloeosporioides and F. avenaceum. Analysis of diversity indices indicated that C. chinensis harbored abundant fungal resources. Methanol extracts of fungal endophyte cultures were evaluated for antibacterial activity against S. aureus ATCC 25923 and two other MRSA clinical strains. Nine of 27 endophytic fungi exhibited inhibitory activities against S. aureus ATCC 25923. Among them, Paraboeremia litseae HL-17, Fusarium sp. HL-23, and Fusarium sp. HL-27 exhibited obvious inhibition against the three S. aureus strains. Our findings suggest that the endophytic fungi in C. chinensis have a high diversity and an obvious tissue specificity, and could be of potential interest in screening anti-MRSA agents. To the best of our knowledge, this is the first report on the diversity and anti-MRSA activity of fungal endophytes from C. chinensis.

• MeSH
• Coptis chinensis MeSH
• endofyty genetika   MeSH
• Fusarium * MeSH
• houby MeSH
• methicilin rezistentní Staphylococcus aureus * MeSH
• mikrobiální testy citlivosti MeSH
• Staphylococcus aureus MeSH
• Publikační typ
• časopisecké články MeSH

The mycotoxin zearalenone (ZEA) in food and feed seriously harms human and animal health. How to reduce its toxicity is an important direction of current research on food safety. This study aim to assess the effects of procyanidins (PC) on cell apoptosis caused by ZEA and to clarify the role of Nrf2 in the process. Swine testicle (ST) cells were treated with ZEA (57.5 μmol/L) and/or PC (10 mg/L) for 24 h. Cell viability was detected by CCK-8 assay. Cell apoptosis and the level of ROS were detected by flow cytometry. The expression levels of mRNA and protein was detected by qRT-PCR and western blotting. Our results showed that ZEA reduced the antioxidant capacity of the ST cells, induced the cell apoptosis and inhibited the gene and protein expression of Nrf2 and its downstream genes (ho-1,nqo1), while PC improved the cell antioxidant capacity, reduced the degree of ZEA-induced cell apoptosis and promoted the gene and protein expression of Nrf2 and its downstream genes. However, when the Nrf2 small molecule inhibitor ML385 was added, the ability of PC to inhibit ZEA-induced cell apoptosis and promote the expression of Nrf2 and its downstream genes were decreased. Our results demonstrated that ZEA induced oxidative stress and apoptosis of ST cells, which were alleviated by PC intervention via activating Nrf2 signaling pathway. This finding of this study provided a molecular basis for the clinical application of PC to prevent ZEN-caused reproductive toxicity.

• MeSH
• antioxidancia metabolismus   farmakologie   MeSH
• apoptóza MeSH
• faktor 2 související s NF-E2 genetika   metabolismus   MeSH
• oxidační stres MeSH
• prasata MeSH
• proantokyanidiny * farmakologie   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• signální transdukce MeSH
• testis metabolismus   MeSH
• zearalenon * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Aflatoxin B1 is a mycotoxin that widely exists in feed and has a great impact on human and animal health. This study aimed to examine whether Bacillus amyloliquefaciens B10 protected against aflatoxin B1-induced cecal inflammation in mice. It was found that Bacillus amyloliquefaciens B10 could significantly improve the effects of AFB1 on body weight and intestinal inflammation of mice and enhance the expression of tight-junction protein. Compared with the CON group, the combination of AFB1 and B10 significantly increased the abundance of Actinobacteria and Bacilli in a collaborative manner, and significantly reduced the abundance of Ruminococcae, Lactobacillaceae and Clostridia. Meanwhile, the results showed that the abundance of Bacterides and Bacterdia in AFB1 + B10 group was significantly lower than that of AFB1 group, and the Firmicutes increased significantly. Bacillus amyloliquefaciens B10 can be used as a feed additive and alleviate cecal inflammation induced by AFB1 in mice by regulating intestinal flora.

• MeSH
• aflatoxin B1 antagonisté a inhibitory   MeSH
• Bacillus amyloliquefaciens fyziologie   MeSH
• cékum patologie   MeSH
• myši MeSH
• střevní mikroflóra * MeSH
• zánět prevence a kontrola   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Interleukin-2 is a pleiotropic cytokine that mediates both pro- and anti-inflammatory functions. Immune cells naturally differ in their sensitivity to IL-2 due to cell type and activation state-dependent expression of receptors and signaling pathway components. To probe differences in IL-2 signaling across cell types, we used structure-based design to create and profile a series of IL-2 variants with the capacity to titrate maximum signal strength in fine increments. One of these partial agonists, IL-2-REH, specifically expanded Foxp3+ regulatory T cells with reduced activity on CD8+ T cells due to cell type-intrinsic differences in IL-2 signaling. IL-2-REH elicited cell type-dependent differences in gene expression and provided mixed therapeutic results: showing benefit in the in vivo mouse dextran sulfate sodium (DSS) model of colitis, but no therapeutic efficacy in a transfer colitis model. Our findings show that cytokine partial agonists can be used to calibrate intrinsic differences in response thresholds across responding cell types to narrow pleiotropic actions, which may be generalizable to other cytokine and growth factor systems.

• MeSH
• buněčné linie MeSH
• CD8-pozitivní T-lymfocyty metabolismus   MeSH
• cytokiny metabolismus   MeSH
• interleukin-2 agonisté   metabolismus   MeSH
• kolitida chemicky indukované   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• regulační T-lymfocyty metabolismus   MeSH
• signální transdukce * MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

Sexual dimorphism in cancer incidence and outcome is widespread. Understanding the underlying mechanisms is fundamental to improve cancer prevention and clinical management. Sex disparities are particularly striking in kidney cancer: across diverse populations, men consistently show unexplained 2-fold increased incidence and worse prognosis. We have characterized genome-wide expression and regulatory networks of 609 renal tumors and 256 non-tumor renal tissues. Normal kidney displayed sex-specific transcriptional signatures, including higher expression of X-linked tumor suppressor genes in women. Sex-dependent genotype-phenotype associations unraveled women-specific immune regulation. Sex differences were markedly expanded in tumors, with male-biased expression of key genes implicated in metabolism, non-malignant diseases with male predominance and carcinogenesis, including markers of tumor infiltrating leukocytes. Analysis of sex-dependent RCC progression and survival uncovered prognostic markers involved in immune response and oxygen homeostasis. In summary, human kidney tissues display remarkable sexual dimorphism at the molecular level. Sex-specific transcriptional signatures further shape renal cancer, with relevance for clinical management.

• MeSH
• celogenomová asociační studie MeSH
• genetická predispozice k nemoci * MeSH
• genetické asociační studie MeSH
• geny vázané na chromozom X MeSH
• karcinom z renálních buněk genetika   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery metabolismus   MeSH
• nádory ledvin genetika   metabolismus   MeSH
• pohlavní dimorfismus * MeSH
• prognóza MeSH
• progrese nemoci MeSH
• regulace genové exprese u nádorů * MeSH
• senioři MeSH
• stanovení celkové genové exprese * MeSH
• tumor supresorové geny MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Renal cell carcinoma (RCC) has an undisputed genetic component and a stable 2:1 male to female sex ratio in its incidence across populations, suggesting possible sexual dimorphism in its genetic susceptibility. We conducted the first sex-specific genome-wide association analysis of RCC for men (3227 cases, 4916 controls) and women (1992 cases, 3095 controls) of European ancestry from two RCC genome-wide scans and replicated the top findings using an additional series of men (2261 cases, 5852 controls) and women (1399 cases, 1575 controls) from two independent cohorts of European origin. Our study confirmed sex-specific associations for two known RCC risk loci at 14q24.2 (DPF3) and 2p21(EPAS1). We also identified two additional suggestive male-specific loci at 6q24.3 (SAMD5, male odds ratio (ORmale) = 0.83 [95% CI = 0.78-0.89], Pmale = 1.71 × 10-8 compared with female odds ratio (ORfemale) = 0.98 [95% CI = 0.90-1.07], Pfemale = 0.68) and 12q23.3 (intergenic, ORmale = 0.75 [95% CI = 0.68-0.83], Pmale = 1.59 × 10-8 compared with ORfemale = 0.93 [95% CI = 0.82-1.06], Pfemale = 0.21) that attained genome-wide significance in the joint meta-analysis. Herein, we provide evidence of sex-specific associations in RCC genetic susceptibility and advocate the necessity of larger genetic and genomic studies to unravel the endogenous causes of sex bias in sexually dimorphic traits and diseases like RCC.

• MeSH
• celogenomová asociační studie * MeSH
• genetická predispozice k nemoci * MeSH
• jednonukleotidový polymorfismus MeSH
• karcinom z renálních buněk epidemiologie   genetika   MeSH
• lidé MeSH
• lokus kvantitativního znaku MeSH
• nádory ledvin epidemiologie   genetika   MeSH
• odds ratio MeSH
• sexuální faktory MeSH
• výpočetní biologie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

BACKGROUND: Several obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation. METHODS AND FINDINGS: Genetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (ORSD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (ORSD: 1.56, 95% confidence interval [CI] 1.44-1.70), with comparable results for waist-to-hip ratio (ORSD: 1.63, 95% CI 1.40-1.90) and body fat percentage (ORSD: 1.66, 95% CI 1.44-1.90). This analysis further indicated that higher fasting insulin (ORSD: 1.82, 95% CI 1.30-2.55) and diastolic blood pressure (DBP; ORSD: 1.28, 95% CI 1.11-1.47), but not systolic blood pressure (ORSD: 0.98, 95% CI 0.84-1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose. CONCLUSIONS: This study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk.

• MeSH
• celogenomová asociační studie MeSH
• diabetes mellitus 2. typu komplikace   MeSH
• genetické markery MeSH
• index tělesné hmotnosti MeSH
• inzulin krev   MeSH
• karcinom z renálních buněk etiologie   genetika   MeSH
• krevní glukóza analýza   MeSH
• krevní tlak MeSH
• lidé MeSH
• lipidy krev   MeSH
• mendelovská randomizace MeSH
• nádory ledvin etiologie   genetika   MeSH
• obezita komplikace   genetika   MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH

Corn silk (Stigma maydis) contains many bioactive and functional ingredients and has many health benefit effects. This commodity is of a great value and has a good prospect in research and market. In addition, corn silk can also contribute to the development of environmental protection. This review deals with the research findings on the extraction technology of corn silk bioactive ingredients. It also covers anti-oxidative activity, anti-diabetic effects, antitumor capacity, and other health benefit effects of corn silk, as well as the issue of toxicity and metal ions adsorption effects. Last but not least, this review discusses market status and future prospect of corn silk.

• Klíčová slova
• kukuřičné hedvábí,
• MeSH
• antioxidancia terapeutické užití   MeSH
• antitumorózní látky MeSH
• fytoterapie * metody   MeSH
• hypoglykemika MeSH
• kukuřice setá * MeSH
• léčivé rostliny * MeSH
• lidé MeSH
• rostlinné extrakty terapeutické užití   MeSH
• Check Tag
• lidé MeSH

BACKGROUND: Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings. OBJECTIVE: We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations. DESIGN, SETTING, AND PARTICIPANTS: Genotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis. RESULTS AND LIMITATIONS: Longer genetically inferred telomere length was associated with an increased risk of RCC (OR=2.07 per predicted kilobase increase, 95% confidence interval [CI]:=1.70-2.53, p<0.0001). As a sensitivity analysis, we excluded two telomere length variants in linkage disequilibrium (R2>0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR=1.73, 95% CI=1.36-2.21, p<0.0001). Exploratory analyses for individual histologic subtypes suggested comparable associations with the telomere length GRS for clear cell (N=5573, OR=1.93, 95% CI=1.50-2.49, p<0.0001), papillary (N=573, OR=1.96, 95% CI=1.01-3.81, p=0.046), and chromophobe RCC (N=203, OR=2.37, 95% CI=0.78-7.17, p=0.13). CONCLUSIONS: Our investigation adds to the growing body of evidence indicating some aspect of longer telomere length is important for RCC risk. PATIENT SUMMARY: Telomeres are segments of DNA at chromosome ends that maintain chromosomal stability. Our study investigated the relationship between genetic variants associated with telomere length and renal cell carcinoma risk. We found evidence suggesting individuals with inherited predisposition to longer telomere length are at increased risk of developing renal cell carcinoma.

• MeSH
• celogenomová asociační studie MeSH
• fenotyp MeSH
• genetická predispozice k nemoci MeSH
• hodnocení rizik MeSH
• homeostáza telomer * MeSH
• jednonukleotidový polymorfismus * MeSH
• karcinom z renálních buněk krev   genetika   patologie   MeSH
• leukocyty chemie   MeSH
• lidé MeSH
• mendelovská randomizace MeSH
• nádory ledvin krev   genetika   patologie   MeSH
• odds ratio MeSH
• rizikové faktory MeSH
• studie případů a kontrol MeSH
• telomery genetika   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH

Previous genome-wide association studies (GWAS) have identified six risk loci for renal cell carcinoma (RCC). We conducted a meta-analysis of two new scans of 5,198 cases and 7,331 controls together with four existing scans, totalling 10,784 cases and 20,406 controls of European ancestry. Twenty-four loci were tested in an additional 3,182 cases and 6,301 controls. We confirm the six known RCC risk loci and identify seven new loci at 1p32.3 (rs4381241, P=3.1 × 10-10), 3p22.1 (rs67311347, P=2.5 × 10-8), 3q26.2 (rs10936602, P=8.8 × 10-9), 8p21.3 (rs2241261, P=5.8 × 10-9), 10q24.33-q25.1 (rs11813268, P=3.9 × 10-8), 11q22.3 (rs74911261, P=2.1 × 10-10) and 14q24.2 (rs4903064, P=2.2 × 10-24). Expression quantitative trait analyses suggest plausible candidate genes at these regions that may contribute to RCC susceptibility.

• MeSH
• běloši genetika   MeSH
• celogenomová asociační studie * MeSH
• dospělí MeSH
• fenotyp MeSH
• genetická predispozice k nemoci * MeSH
• genetické lokusy MeSH
• jednonukleotidový polymorfismus MeSH
• karcinom z renálních buněk genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory ledvin genetika   MeSH
• senioři MeSH
• zárodečné mutace MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH