Accumulation and metabolism of selenium in the rare yeast Kazachstania unispora during the selenium enrichment process.

Selenium (Se)-enriched yeast is a good nutritional source for human being. Kazachstania unispora (K. unispora) has shown the positive physiological functionality for human health, whose potential for Se enrichment, however, remains elusive. This study demonstrated the ability of K. unispora to convert inorganic Se to organic Se, and then comprehensively investigated the accumulation and metabolism of Se in K. unispora. The results indicated that K. unispora can effectively accumulate organic Se, of which 95% of absorbed Se was converted to organic forms. Among these organic Se, 46.17% of them was bound to protein and 16.78% was combined with polysaccharides. In addition, some of the organic Se was metabolized to selenomethionine (30.26%) and selenocystine (3.02%), during which four low-molecular weight selenometabolites were identified in K. unispora. These findings expand the scope of Se-enriched yeast species, and provide useful knowledge for further investigation of Se enrichment mechanism in K. unispora.

Association of the American Heart Association's new "Life's Essential 8" with all-cause mortality in patients with chronic kidney disease: a cohort study from the NHANES 2009-2016.

BACKGROUND: People with chronic kidney disease (CKD) are more likely to die prematurely, and this increased risk of death is primarily attributable to deaths from cardiovascular disease (CVD). We aim to investigate the relationship between Life's Essential 8 (LE8), a newly proposed cardiovascular health (CVH) measurement system, and all-cause mortality of CKD patients among US adults. METHODS: A total of 3,169 CKD patients aged 20 and older from the National Health and Nutritional Examination Survey in 2009-2016 were involved in this study. Participants were divided into low (0-49), moderate (50-79) and high (80-100) CVH groups according to LE8 score (range 0-100). The mortality was ascertained from the National Death Index. Cox proportional hazards regression and restricted cubic spline were used to investigate the relationship. RESULTS: Among the 3,169 CKD patients, the median age was 66.0 (25.0) years and 1,671 (52.7%) were female, and the median follow-up time was 6.00 years. The median LE8 score of the study cohort was 57.5 (19.4). CKD patients with low CVH, health behavior (HB) and health factors (HF) scores presented with higher all-cause mortality (both log-rank P-values < 0.001). After adjusted for multiple confounders, patients in higher CVH group had a lower risk of all-cause mortality, with a HR (95%CI) of 0.32 (0.19-0.55). Similar results were observed in high HB group [HR 0.36 (0.25-0.50)]. The restricted cubic spline showed a significant inverse relationship between LE8, HB and HF scores with CKD all-cause mortality, while the protective effect seemed weaker for HF score. Above results remained robust in the sensitivity analysis. Stronger inverse associations were revealed in middle-aged patients and patients with higher education levels. CONCLUSIONS: LE8 and its subscales scores were inversely associated with all-cause mortality in patients with CKD. Promoting CVH in CKD patients is a potential way to improve their long-term survival rate.

Vibration Emissions Reduce Boar Sperm Quality via Disrupting Its Metabolism.

Artificial insemination (AI) with liquid-preserved semen has recently become common in pig breeding. The semen doses are produced in a centralized manner at the boar stud and then subsequently distributed and transported to sow farms. However, vibration emissions during transportation by logistic vehicles may adversely affect the quality of boar sperm. Therefore, this study aimed to explore the impact of vibration-induced emissions on sperm quality and function under simulated transportation conditions. Each time, ejaculates from all 15 boars were collected and then pooled together to minimize individual variations, and the sample was split using an extender for dilution. Different rotational speeds (0 rpm, 80 rpm, 140 rpm, 200 rpm) were utilized to simulate varying intensities of vibration exposure using an orbital shaker, considering different transportation times (0 h, 3 h, and 6 h). Subsequently, evaluations were conducted regarding sperm motility, plasma membrane integrity, acrosome integrity, mitochondrial function, adenosine triphosphate (ATP) levels, mitochondrial reactive oxygen species (ROS) levels, pH, glycolytic pathway enzyme activities, and capacitation following exposure to vibration emissions. Both vibration time and intensity impact sperm motility, plasma membrane integrity, and acrosomal integrity. Vibration exposure significantly reduced sperm ATP levels, mitochondrial membrane potential, and the levels of mitochondria-encoded proteins (MT-ND1, MT-ND6) (p < 0.05). After vibration emission treatment, the pH value and mitochondrial ROS levels significantly increased (p < 0.05). Inhibition of sperm glycolysis was observed, with reduced activities of hexokinase (HK), pyruvate kinase (PK), and lactate dehydrogenase (LDH), along with decreased lactate levels (p < 0.05). Additionally, sperm tyrosine phosphorylation levels were significantly reduced by vibration emissions compared to the control group (p < 0.05). After the vibration emission treatment, the number of sperm bound to each square millimeter of oviduct explants decreased significantly compared to the control group (p < 0.05). Similarly, compared to the control group, using semen subjected to vibration stress for AI results in significantly reduced pregnancy rates, total born litter size, live-born litter size, and healthy born litter size (p < 0.05).

Coffee consumption might be associated with lower potential risk and severity of metabolic syndrome: national health and nutrition examination survey 2003-2018.

BACKGROUND: Metabolic syndrome (MetS) is a clinical syndrome characterized by multiple metabolic disorders and is a serious global health problem. The coffee effect, acting as one of the most prevalent beverages on metabolic syndrome, is debatable. METHODS: We included patients from the National Health and Nutrition Examination Survey 2003-2018 and used a comprehensive evaluation called the MetS z-score to assess the severity of metabolic syndrome. The relationship between coffee, decaffeinated coffee, tea, and MetS z-scores was explored using a weighted linear regression. We also divided the participants into metabolic and non-metabolic syndrome groups according to the NCEP/ATP III criteria for the subgroup analysis. RESULTS: A total of 14,504 participants were included in this study. The results demonstrated that drinking more than three cups of coffee daily was significantly linked to lower MetS z-scores (p < 0.001). Daily coffee consumption was also associated with lower BMI (p = 0.02), systolic blood pressure (p < 0.001), Homeostatic Model Assessment for Insulin Resistance (p < 0.001), and triglycerides (p < 0.001), while it was positively correlated with HDL-C (p = 0.001). Participants who consumed more than three cups of coffee daily had a lower MetS z-score in the MetS (p < 0.001) and non-MetS (p = 0.04) groups. CONCLUSION: This research indicates that coffee consumption is linked to MetS severity. However, decaffeinated coffee and tea intake were unrelated to MetS severity.

Assessment of the correlation between KAP scores regarding sugar-sweetened beverage consumption and hyperuricemia amongst Chinese young adults.

BACKGROUND: The prevalence of hyperuricemia in China has been consistently increasing, particularly among the younger generation. The excessive consumption of sugar-sweetened beverages is associated with hyperuricemia. This study examined the knowledge, attitudes, and practices (KAP) of Chinese young adults regarding sugar-sweetened beverage consumption and the correlation with hyperuricemia. METHODS: This cross-sectional investigation was conducted from June 28th, 2023, to July 21st, 2023, and enrolled Chinese young adults. Demographics and KAP were evaluated using a questionnaire (Cronbach's α = 0.787). Factors influencing KAP scores were analyzed using multivariable analyses. RESULTS: A total of 1288 valid questionnaires were analyzed. The median knowledge, attitude, and practice scores were 16 (12,19)/22, 22 (20,24)/30, and 27.5 (23,31.75)/40. The multivariable analysis showed that bachelor's/associate education (OR = 1.912, 95%CI: 1.128-3.239), white collar/employee (OR = 0.147, 95%CI: 0.105-0.206), educator (OR = 0.300, 95%CI: 0.174-0.518), healthcare worker (OR = 0.277, 95%CI: 0.188-0.407), not suffering from hyperuricemia (OR = 0.386, 95%CI: 0.253-0.590), and not having gout (OR = 0.456, 95%CI: 0.282-0.736) were independently associated with knowledge. Age 26-30 (OR = 1.470, 95%CI: 1.052-2.052), age 31-35 (OR = 1.489, 95%CI: 1.097-2.022), age 36-40 (OR = 0.328, 95%CI: 1.010-1.746), age 41-44 (OR = 1.548, 95%CI: 1.091-2.198), and not having hyperuricemia (OR = 0.512, 95%CI: 0.345-0.760) were independently associated with attitude. White collar/employee (OR = 0.386, 95%CI: 0.285-0.521), educator (OR = 0.534, 95%CI: 0.317-0.899), healthcare worker (OR = 0.341, 95%CI: 0.236-0.493), having siblings (OR = 0.725, 95%CI: 0.573-0.917), and not suffering from hyperuricemia (OR = 0.442, 95%CI: 0.296-0.659), were independently associated with practice. CONCLUSION: Chinese young adults display moderate KAP toward sugar-sweetened beverages. Notably, an association was observed between hyperuricemia and each KAP dimension.

Preparation and characterization of pectin-alginate-based microbeads reinforced by nano montmorillonite filler for probiotics encapsulation: Improving viability and colonic colonization.

Hydrogel microbeads can be used to enhance the stability of probiotics during gastrointestinal delivery and storage. In this study, the pectin-alginate hydrogel was enhanced by adding montmorillonite filler to produce microbeads for encapsulating Lactobacillus kefiranofaciens (LK). Results showed that the viscosity of biopolymer solutions with 1 % (PAMT1) and 3 % (PAMT3) montmorillonite addition was suitable for producing regular-shaped microbeads. A layered cross-linked network was formed on the surface of PAMT3 microbeads through electrostatic interaction between pectin-alginate and montmorillonite filler, and the surrounding LK with adsorbed montmorillonite was encapsulated inside the microbeads. PAMT3 microbeads reduced the loss of viability of LK when passing through the gastric acid environment, and facilitated the slow release of LK in the intestine and colonic colonization. The maximum decrease in viability among all filler groups was 1.21 log CFU/g after two weeks of storage, while PAMT3 freeze-drying microbeads only decreased by 0.46 log CFU/g, indicating that the gel layer synergized with the adsorbed layer to provide dual protection for probiotics. Therefore, filler-reinforced microbeads are a promising bulk encapsulation carrier with great potential for the protection and delivery of probiotics and can be developed as food additives for dairy products.

Regulation of Gut Microbiota and Microbial Metabolome of Kefir Supernatant against Fusobacterium nucleatum and DSS-Coinduced Colitis.

The aim of this study was to investigate the intervention effect of kefir supernatant (KS) on the initiation and progression of an ulcerative colitis (UC) murine model. We established an UC murine model by orally administrating with 109 CFUs of Fusobacterium nucleatum for 3 weeks and 3% dextran sulfate sodium (DSS) treatment in the third week. KS was used to intervene in this colitis model. Our results showed that KS supplementation ameliorated the symptoms, restrained the secretion of pro-inflammatory cytokines (TNF-α, IL-6, and IL-17F), promoted the release of anti-inflammatory cytokines (IL-4 and IL-10), and ameliorated oxidative stress. Furthermore, the increased number of goblet cells and upregulated expression of MUC2, occludin and claudin-1 indicated that the colon barrier was protected by KS. Additionally, KS supplementation mitigated gut microbiota dysbiosis in the UC murine model, leading to an increase in the abundance of Blautia and Akkermansia and a decrease in the level of Bacteroides. The altered gut microbiota also affected colon metabolism, with differential metabolites mainly associated with the biosynthesis of the l-arginine pathway. This study revealed that KS supplementation restored the community structure of gut microbiota, altered the biosynthesis of l-arginine, and thereby modulated the process of colonic inflammation.

Role of Chemotaxis of Vδ2 T Cells to the Synovium in the Pathogenesis of Acute Gouty Arthritis.

Background: This study aimed to explore the potential roles of Vδ2 T cells in the pathogenesis of acute gouty arthritis. Methods: Patients with gout (n=86), rheumatoid arthritis (n=7), osteoarthritis (n=9), and healthy controls (n=40) were enrolled. γδT cell frequency, chemokine receptor expression and production of pro-inflammatory cytokines in cells from peripheral blood and synovial fluid samples were quantified by flow cytometry. The chemotaxis ability of Vδ2 T cells was determined by transwell migration assay. The levels of chemokines were also detected by enzyme-linked immunosorbent assay. Results: Peripheral Vδ2 T cells had significantly lower frequencies in acute gout patients than that in healthy controls (P<0.001). These peripheral Vδ2 T cells were negatively correlated with inflammatory markers. Vδ2 T cells from acute gout patients accumulated in synovial fluid, as evidenced by a higher abundance of Vδ2 T cells in it than that in the serum (P<0.01). And Vδ2 T cells expressed a high level of C-X-C chemokine receptor 3 (P=0.035), and its corresponding chemokine C-X-C motif chemokine ligand 10 showed a high concentration in synovial fluid (P<0.05). Vδ2 T cells from synovial fluid of acute gout patients produced a high level of interleukin-17 (P=0.033). Conclusion: The up-regulated expression of C-X-C chemokine receptor 3 on Vδ2 T cells potentially facilitates their infiltration into synovial fluid during acute gouty arthritis. Further production of interleukin-17 by Vδ2 T cells may contribute to the pathogenesis of gout. This study sheds new light on developing novel Vδ2 T cells-based therapeutic strategies for gout treatment.

Microflora structure and functional capacity in Tibetan kefir grains and selenium-enriched Tibetan kefir grains: A metagenomic analysis.

Tibetan kefir grains (TKGs) are a complex protein-lipid-polysaccharide matrix composed of various microorganisms. Microorganisms have the benefit of being effective, secure, and controllable when used for selenium enrichment. In this study, selenium-enriched Tibetan kefir grains (Se-TKGs) were made, and the microbiology composition was analyzed through a metagenomic analysis, to explore the influence of selenium enrichment. The microbial composition of TKGs and Se-TKGs, as well as the probiotic species, quorum sensing system (QS) and functional genes were compared and evaluated. Lactobacillus kefiranofaciens was the most abundant microbial species in both communities. Compared with TKGs, Se-TKGs had a much higher relative abundance of acetic acid bacteria. Lactobacillus helveticus was the most common probiotic species both in TKGs and Se-TKGs. Probiotics with antibacterial and anti-inflammatory properties were more abundant in Se-TKGs. QS analysis revealed that Se-TKGs contained more QS system-associated genes than TKGs. Moreover, Kyoto Encyclopedia of Genes and Genomes analysis revealed that the pathway for human disease ko01501 had the greatest relative abundance in both TKGs and Se-TKGs. Compared with TKGs, Se-TKGs demonstrated a greater relative abundance of different drug resistance-related metabolic pathways. Additionally, linear discriminant analysis effect size was used to examine the biomarkers responsible for the difference between the two groups. In this study, we focused on the microbiological structure of TKGs and Se-TKGs, with the aim of establishing a foundation for a more thorough investigation of Se-TKGs and providing a basis for exploring potential future use.

Micro-inflammation related gene signatures are associated with clinical features and immune status of fibromyalgia.

BACKGROUND: Fibromyalgia (FM) is a multifaceted disease. Along with the genetic, environmental and neuro-hormonal factors, inflammation has been assumed to have role in the pathogenesis of FM. The aim of the present study was to explore the differences in clinical features and pathophysiology of FM patients under different inflammatory status. METHODS: The peripheral blood gene expression profile of FM patients in the Gene Expression Omnibus database was downloaded. Differentially expressed inflammatory genes were identified, and two molecular subtypes were constructed according to these genes used unsupervised clustering analysis. The clinical characteristics, immune features and pathways activities were compared further between the two subtypes. Then machine learning was used to perform the feature selection and construct a classification model. RESULTS: The patients with FM were divided into micro-inflammation and non-inflammation subtypes according to 54 differentially expressed inflammatory genes. The micro-inflammation group was characterized by more major depression (p = 0.049), higher BMI (p = 0.021), more active dendritic cells (p = 0.010) and neutrophils. Functional enrichment analysis showed that innate immune response and antibacterial response were significantly enriched in micro-inflammation subtype (p < 0.050). Then 5 hub genes (MMP8, ENPP3, MAP2K3, HGF, YES1) were screened thought three feature selection algorithms, an accurate classifier based on the 5 hub DEIGs and 2 clinical parameters were constructed using support vector machine model. Model scoring indicators such as AUC (0.945), accuracy (0.936), F1 score (0.941), Brier score (0.079) and Hosmer-Lemeshow goodness-of-fit test (χ2 = 4.274, p = 0.832) proved that this SVM-based classifier was highly reliable. CONCLUSION: Micro-inflammation status in FM was significantly associated with the occurrence of depression and activated innate immune response. Our study calls attention to the pathogenesis of different subtypes of FM.

Hyperuricemia and gout increased the risk of long-term mortality in patients with heart failure: insights from the National Health and Nutrition Examination Survey.

BACKGROUND: The prevalence of hyperuricemia, gout, and heart failure (HF) is on the rise, and these conditions often share similar risk factors. The present study aimed to evaluate the relationship among hyperuricemia, gout, HF, and all-cause mortality. METHODS: The data on nonpregnant participants aged ≥ 20 years with or without hyperuricemia, gout, and HF from the National Health and Nutrition Examination Survey 2001-2018 and 2007-2018 were included in this study. The binary logistic regression, Kaplan-Meier curve, Cox proportional-hazards model, and restricted cubic spline analysis were employed to evaluate the relationship among hyperuricemia, gout, HF, and all-cause mortality. RESULTS: Of 204,179,060 and 223,702,171 weighted eligible participants, 40,044,228 (19.6%) and 9,158,600 (4.1%) had hyperuricemia and gout, respectively. Older age, diabetes, stroke, and coronary artery disease were the risk factors for HF among patients with hyperuricemia and gout. The median survival time was 7.00 years and 6.25 years and the 5-year survival rate was 59.9% and 55.9% for patients with HF and hyperuricemia and those with HF and gout, respectively. Patients with hyperuricemia or gout were 2.46 and 2.35 times more likely to have HF and 1.37 and 1.45 times more likely to experience all-cause mortality compared with those who did not exhibit these conditions. The restricted cubic spline showed a nonlinear correlation between uric acid levels and HF and a J-shaped correlation between uric acid levels and all-cause mortality. CONCLUSIONS: Ambulatory patients with hyperuricemia or gout were more likely to have HF compared with those without hyperuricemia or gout. Patients with HF with hyperuricemia or gout were more likely to experience all-cause mortality in the long-term follow-up.

Characteristics and Outcomes of Anti-interferon Gamma Antibody-Associated Adult Onset Immunodeficiency.

PURPOSE: Anti-interferon gamma antibody (AIGA) is a rare cause of adult onset immunodeficiency, leading to severe disseminated opportunistic infections with varying outcomes. We aimed to summarize the disease characteristics and to explore factors associated with disease outcome. METHODS: A systematic literature review of AIGA associated disease was conducted. Serum-positive cases with detailed clinical presentations, treatment protocols, and outcomes were included. The patients were categorized into controlled and uncontrolled groups based on their documented clinical outcome. Factors associated with disease outcome were analyzed with logistic regression models. RESULTS: A total of 195 AIGA patients were retrospectively analyzed, with 119(61.0%) having controlled disease and 76 (39.0%) having uncontrolled disease. The median time to diagnosis and disease course were 12 months and 28 months, respectively. A total of 358 pathogens have been reported with nontubercular mycobacterium (NTM) and Talaromyces marneffei as the most common pathogens. The recurrence rate was as high as 56.0%. The effective rates of antibiotics alone, antibiotics with rituximab, and antibiotics with cyclophosphamide were 40.5%, 73.5%, and 75%, respectively. In the multivariate logistic analysis, skin involvement, NTM infection, and recurrent infections remained significantly associated with disease control, with ORs of 3.25 (95% CI 1.187 ~ 8.909, P value = 0.022), 4.74 (95% CI 1.300 ~ 17.30, P value = 0.018), and 0.22 (95% CI 0.086 ~ 0.551, P value = 0.001), respectively. The patients with disease control had significant AIGA titer reduction. CONCLUSIONS: AIGA could cause severe opportunistic infections with unsatisfactory control, particularly in patients with recurrent infections. Efforts should be made to closely monitor the disease and regulate the immune system.

Prevalence of common chronic disease and multimorbidity patterns in Guangdong province with three typical cultures: analysis of data from the Diverse Life-Course Cohort study.

Background: Variations in the prevalence and pattern of multimorbidity might be attributable to lifestyle and environmental factors. This study was performed to determine the prevalence of common chronic diseases and to reveal multimorbidity patterns among adults in Guangdong province with Chaoshan, Hakka, and island cultures. Methods: We used data collected at the baseline survey (April-May 2021) of the Diverse Life-Course Cohort study and included 5,655 participants aged ≥20 years. Multimorbidity was defined as the presence of two or more of the 14 chronic diseases collected by self-reports, physical examinations, and blood tests. Multimorbidity patterns were explored by association rule mining (ARM). Results: Overall, 40.69% of participants had multimorbidity, and the prevalence among coastland (42.37%) and mountain residents (40.36%) was higher than that among island residents (37.97%). The prevalence of multimorbidity increased rapidly with higher age groups and showed an inflection point at 50 years, beyond which >50% of the middle-aged and older adults had multimorbidity. The proportion of people with two chronic diseases accounted for most cases of multimorbidity, and the strongest association was found between hyperuricemia and gout (lift of 3.26). The most prevalent multimorbidity pattern was dyslipidemia and hyperuricemia in the coastland areas and dyslipidemia combined with hypertension in the mountain and island areas. Furthermore, the most common triad combination consisted of cardiovascular diseases, gout, and hyperuricemia, which was verified in the mountain and coastal areas. Conclusion: These observations of multimorbidity patterns, including the most frequent multimorbidity and associations, will help healthcare providers develop healthcare plans that improve the effectiveness of multimorbidity management.

Lower Serum Uric Acid Levels May Lower the Incidence of Diabetic Chronic Complications in U.S. Adults Aged 40 and Over.

Previous studies have generally reported the association between serum uric acid (SUA) and diabetic complications, but large-scale research exploring the above association in U.S. adults with diabetes is limited. To explore the association between SUA and chronic complications of diabetes among U.S. patients aged ≥40, we used data from the National Health and Nutrition Examination Survey 1999−2008. SUA was divided into three levels: T1 (SUA ≥ 420 µmol/L), T2 (300 ≤ SUA < 420 µmol/L), and T3 (SUA < 300 µmol/L). Binary logistic regression and restricted cubic spline analysis were applied to evaluate the association between SUA and chronic complications of diabetes. A trend test was performed as the SUA increased substantially. After full-adjusted confounding factors, patients in the T3 group had a lower risk of diabetic kidney disease, cardiovascular disease, and peripheral neuropathy compared with the T1 group, with a OR (95% CIs) of 0.33 (0.21−0.52), 0.56 (0.36−0.87), and 0.49 (0.27−0.89), respectively. The restricted cubic spline showed a significant positive relationship between SUA and cardiovascular disease and diabetic kidney disease in diabetes patients, but not peripheral neuropathy. Maintaining a SUA of less than 300 µmol/L might be protective against the risk of cardiovascular disease, diabetic kidney disease, and peripheral neuropathy other than diabetic retinopathy compared with a SUA of more than 420 µmol/L in U.S. diabetes patients aged 40 and over.

Aspergillus cristatus attenuates DSS-induced intestinal barrier damage through reducing the oxidative stress, regulating short-chain fatty acid and inhibiting MAPK signaling pathways.

BACKGROUND: Probiotics are regarded as a promising strategy for relieving colitis caused by dextran sulfate sodium (DSS). One of the dominant probiotic fungi in Fuzhuan brick tea is identified as Aspergillus cristatus, but whether it can effectively improve colitis remains poorly understood. Here, the improving effect of A. cristatus on colitis was investigated. RESULTS: Our results showed that A. cristatus intervention prominently alleviated gut damage as evidenced by the inhibition of shortened colon length, goblet cell depletion, and histological injury. Mechanistically, after administration with low concentrations of A. cristatus H-1 and A. cristatus S-6, the expression of interleukin-6, tumor necrosis factor-α, interleukin-1ß, nitric oxide, and malondialdehyde were significantly downregulated, and the content of glutathione, catalase, interleukin-10, immunoglobulin G, claudin-1, occludin, and zonula occludens-1 were effectively upregulated. More importantly, live A. cristatus supplementation lightened DSS-induced gut barrier damage by suppressing activation of the mitogen-activated protein kinase (MAPK) signaling pathway, increasing the synthesis of short-chain fatty acids (SCFAs) and stimulating the increase in peroxisome proliferator-activated receptor γ expression. CONCLUSION: Together, A. cristatus can attenuate DSS-induced intestinal barrier damage through reducing the oxidative stress, regulating SCFA and inhibiting MAPK signaling pathways (P38/JNK/ERK). Our findings indicate that A. cristatus replenishment has potential as a new probiotic fungi to reduce DSS-induced colitis. © 2022 Society of Chemical Industry.

Time- and concentration-dependent stimulation of oxidative stress in chondrocytes by intracellular soluble urate.

BACKGROUND: Gout could result in irreversible bone erosion, and chondrocyte might be involved in the process. Increased soluble urate is the early stage of gout and is strongly oxidative. OBJECTIVE: To explore the effect of intracellular urate on the oxidative status of chondrocytes Methods: A chondrocyte model was used. Serial concentrations of exogenous urate were incubated with chondrocytes for increasing amounts of time. Reactive oxygen species (ROS), oxidant, and anti-oxidant molecules were measured with biochemical assays, rt-PCR, and western blot. A urate transport inhibitor and oxidative inhibitors were used to confirm the effect of exogenous urate. RESULTS: All concentrations of exogenous urate stimulated the production of ROS in a time- and concentration-dependent manner, as well as oxidant molecules, including hydrogen peroxide (H2O2), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, nitric oxide (NO) inducible nitric oxide synthase (iNOS), and these effects, could be inhibited by oxidant inhibitors. However, anti-oxidant molecules, including acidic leucine-rich nuclear phosphoprotein-32A (ANP32A), ataxia-telangiectasia mutated (ATM), heme oxygenase-1 (HO-1), and the transcription factor nuclear factor erythroid 2 (NF-E2)-related (Nrf2), was decreased by high concentrations of exogenous urate after prolonged incubation, but not by low to medium concentrations of exogenous urate. By inhibiting soluble urate trafficking, benzbromarone significantly suppressed the effect of urate stimulus on the oxidant and anti-oxidant molecules. CONCLUSION: Intracellular soluble urate could regulate chondrocyte redox balance in a time and concentration-dependent manner, and would be a target for regulating and protecting chondrocyte function in the early gout stage.

Assessment of causal associations between uric acid and 25-hydroxyvitamin D levels.

Background: Previous observational studies have revealed the association between serum uric acid and 25-hydroxyvitamin D. However, the causality and the direction of the associations remain unknown. Thus, we performed a two-sample bidirectional Mendelian Randomization (MR) analysis to investigate the causal association between uric acid and 25-hydroxyvitamin D and to determine the direction of the association. Method: Based on the summary-level GWAS data from large genome-wide association studies, several steps were taken in our analysis to select eligible single-nucleotide polymorphisms (SNPs), which were strongly related to exposure as the instrumental variables. We used different analytical methods, such as inverse-variance weighting (IVW) method, weighted median, MR-Egger regression, and weighted mode method, to make our result more robust and reliable. The IVW method was used as the primary analysis. The Cochran's Q test, MR-Egger intercept test, MR-PRESSO method, and "leave-one-out" sensitivity analysis was performed to evaluate the heterogeneities, horizontal pleiotropy, and robustness of the results. MR analyses were also conducted using genetic risk scores (GRS) as instrumental variables in both directions by using the same summary-level GWAS data. Results: Our two-sample MR analysis suggested a causal association of genetically predicted uric acid on 25-hydroxyvitamin D [IVW method: ß(SE), -0.0352(0.0149); p = 0.0178], which suggested that a per mg/dl increase in uric acid was associated with a decrease of 0.74 nmol/L of 25-hydroxyvitamin D, and the above results remained stable in the sensitivity analysis. By contrast, four MR methods suggested no causal relationship of 25-hydroxyvitamin D on serum uric acid [IVW ß(SE), 0.0139 (0.0635); p = 0.826; MR-Egger ß(SE), 0.0671 (0.108); p = 0.537; weighted median ß(SE), 0.0933 (0.0495); p = 0.0598; weighted mode ß(SE), 0.0562 (0.0463); p = 0.228, respectively]. After excluding the SNPs, which were associated with confounding factors and outlier SNPs, the IVW method suggested that there was still no causal association of 25-hydroxyvitamin D on serum uric acid. The GRS approach showed similar results. Conclusions: Serum uric acid may causally affect the 25-hydroxyvitamin D levels, whereas the causal role of 25-hydroxyvitamin D on uric acid was not supported in our MR analysis. Our findings suggest that increased levels of uric acid should prompt investigation for vitamin D deficiency.

Enrichment and Distribution of Selenium in Pediococcus acidilactici MRS-7: Impact on Its Biochemical Composition, Microstructure, and Gastrointestinal Survival.

Lactic acid bacteria can convert selenium (Se) from inorganic to organic and elemental forms, but the distribution and existence form of organic Se in the bacteria are not clear after Se enrichment, and the effects of selenization on the growth and nutritional value of strains also need to be studied. In this study, Pediococcus acidilactici MRS-7 could absorb up to 67% of inorganic Se and convert most of it into organic Se; about 75% of organic Se was selenoprotein, 2.7% was Se-polysaccharide, and 4.6% was Se-nucleic acid. Additionally, Se-enriched treatment increased the levels of amino acids and essential elements in P. acidilactici MRS-7. Finally, after Se enrichment, Se nanoparticles (SeNPs) were found on the surface of P. acidilactici MRS-7, but they had no harmful effect on its morphology, and its survival during gastrointestinal digestion was not affected, indicating that SeP has potential probiotic value in the food industry.

Ameliorative Effect of Saccharomyces cerevisiae JKSP39 on Fusobacterium nucleatum and Dextran Sulfate Sodium-Induced Colitis Mouse Model.

The aim of this study was to evaluate the ability of the Saccharomyces cerevisiae strain with probiotic properties isolated from Tibetan kefir grains to ameliorate Fusobacterium nucleatum (Fn) infection and dextran sulfate sodium (DSS) treatment-induced murine model of colitis. The tolerance to simulated gastrointestinal conditions, hydrophobicity test, autoaggregation assay, and the antioxidant effect of strains was used to screen one strain with colonization and probiotic potential. The murine model of colitis was established by giving 109 cfu Fn 3 weeks by intragastric administration and 3% DSS in water 1 week before sacrifice. The results indicated that S. cerevisiae JKSP39 (SC) possessed optimal probiotic characteristics in vitro. Supplementation with SC increased the body weight and the expression of anti-inflammatory cytokines (IL-4 and IL-10), while decreasing the disease activity index score and expression of proinflammatory cytokines (TNF-α, IL-6, and IL-17F) in mice undergoing experimental colitis as compared with the colitis model group. Additionally, tight junction proteins and the number of goblet cells per crypt were significantly increased in the SC group, which indicated that the gut barrier was well repaired. The mechanism of SC ameliorating Fn-DSS-induced colitis could be related to the decreased levels of reactive oxygen species (myeloperoxidase, total superoxide dismutase, catalase, H2O2, and malondialdehyde) in the colon, the inhibition of endoplasmic reticulum stress, and the regulation of gut microbiota.

Risk factors of urinary calculi in men with gout.

OBJECTIVE: To investigate risk factors of urinary calculi in men with gout. METHOD: A study was conducted at a tertiary hospital in Beijing from October 2016 to January 2020. Male gouty patients were included. Logistic regression was used to establish the association between patients' characteristics and urinary stone disease. A cluster analysis was performed to identify distinct phenotypes of gout based on nine common comorbidities. RESULT: The prevalence of calculi was 23.6% among 454 patients. Longer disease courses and comorbid dyslipidemia were associated with an increased risk of urinary calculi, with an OR of 2.76 (95% CI 1.40-5.64) (p = 0.004) for patients with a disease course of 10 years or longer compared with those with a disease course of gout shorter than 1 year, and an OR of 1.71 (95% CI 1.04-2.88) (p = 0.039) for patients with dyslipidemia. Three clinical phenotypes were recognized. Cluster C1 consists of patients with large body mass index, dyslipidemia, and abnormal liver function. The prevalence of stone was 23.2%. Patients in cluster C2 had fewer comorbidities and the lowest stone risk (13.5%). Cluster C3 had more cardiovascular comorbidities and the highest prevalence of stone (47.1%). CONCLUSION: Longer disease course and dyslipidemia contribute to stone risk in men with gout. Three distinct phenotypes represent distinct pathophysiological mechanisms underlying stone occurrence, which would help us to optimize gout management. Key points • Patients with gout have higher risks for urinary stones. This study found that longer disease courses and comorbid dyslipidemia were associated with an increased risk of urinary calculi in largely untreated young men with uncontrolled gout. • This study reveals three distinct phenotypes of gout based on comorbidities. Among all, the group with more cardiovascular comorbidities has the highest prevalence of stones.