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Accumulation of the heavy metal Cadmium (Cd) in the ovaries and placenta can affect the structure and function of these organs and induce female reproductive toxicity. This toxicity may be due to Cd’s similarity to estrogen and its ability to disrupt endocrine systems. However, the exact molecular mechanism by which Cd causes reproductive toxicity at the transcriptome level remains poorly understood. Hence, this study aimed to observe Cd-induced reproductive damage at the gene level, scrutinize the repercussions of Cd exposure on oogenesis, and explicate the putative pathogenesis of Cd-induced oogenesis based on Caenorhabditis elegans (C. elegans) as an in vivo model. The results showed that Cd exposure significantly decreased the number of offspring and prolonged the reproductive span of C. elegans. Cd exposure also reduced the number of cells in mitosis and the pachytene and diakinesis stages of meiosis, thereby disrupting oogenesis. Combined with transcriptional sequencing and bioinformatics analysis, a total of 3167 DEmRNAs were identified. Regarding gene expression, cul-6, mum-2, and vang-1 were found to be related to Cd-induced reproductive toxicity, and their competing endogenous RNA networks were constructed. We observed that mutations of mom-2 and vang-1 in the Wnt pathway could induce susceptibility to Cd-caused meiosis injury. In conclusion, the results indicated that Cd could impair the oogenesis of C. elegans and the Wnt pathway might serve as a protective mechanism against Cd reproductive toxicity. These findings contribute to a better understanding of the damaging effects and molecular biological mechanisms of Cd on the human reproductive system.

Abstract Background: Diverticular disease has been inconsistently associated with colorectal cancer risk. We conducted a bidirectional Mendelian randomization study to assess this association. Methods: Forty-three and seventy single-nucleotide polymorphisms associated with diverticular disease and colorectal cancer at the genome-wide significance level (p

Background: Birth weight (BW) is an indicator of fetal growth and development. Previous studies showed inconsistent results on the association of ambient particulate matter (PM) exposure with BW, and the role of maternal thyroid function has not been clarified. Methods: We recruited 1711 gravidas between 2017 and 2019 in Henan, China. All participants were followed up until delivery. Daily concentrations of PM, including PM2.5 and PM10, were evaluated by using the spatial-temporal model. Maternal thyroid hormone (TH) levels were quantified by electrochemiluminescent microparticle immunoassay. Linear regression models were employed to examine the association among PM, BW, and maternal TH. Mediating effects of maternal TH interrelated with PM exposure on BW were investigated by causal mediation analyses. Results: A total of 1049 gravidas were identified. We found that per 10 µg/m3 increase in PM2.5 and PM10 were associated with a decreased BW of 9.941 g, and 7.758 g (PM2.5: 95 %CI: −18.184, −1.698; PM10: 95 %CI: −14.436, −1.080). An inverse correlation of maternal FT4 levels with BW was found, with the pooled β of −319.983 g (95 %CI: −483.216, −156.750). We found a prominent positive correlation between gestational FT4 and PM exposure (PM2.5: β = 0.004, 95 %CI: 0.001, 0.007; PM10: β = 0.003, 95 %CI: 0.000, 0.006). Mediation analysis found that FT4 levels mediated the relationship between maternal PM exposure and BW, ranging from 5.55 % to 15.86 %. Conclusions: Maternal PM exposure may induce a reduction in newborn BW by affecting the maternal TH concentrations.

Abstract Long noncoding RNA (lncRNA) may act as a biomarker to predict the overall survival (OS) of cancer patients. This study is to explore the prognostic signature of gastric cancer based on N7‐methylguanosine‐related lncRNAs to evaluate the prognosis and immune status of patients. The lncRNAs were identified by co‐expression analysis, univariate and, stepwise multivariate Cox regression. Then, patients were divided into the high‐ and low‐risk groups. Time‐dependent receiver operating characteristics, log‐rank test, principal component analysis, and nomogram were used to analyze the risk model. Finally, different immune status between the two groups was revealed by gene set enrichment/variation analysis (GSEA/GSVA), CIBERSORTx, and ESTIMATE algorithm. The difference in tumor mutation burden and drug sensitivity between the two groups was also explored. Three lncRNAs (LINC00412, REPIN1‐AS1, and RPH3AL‐AS1) were employed to construct the prognostic model. The OS rate of the high‐risk group was lower than the low‐risk group. GSEA and GSVA indicated this model was associated with immune‐related function, such as negative regulation of humoral immune response. Furthermore, the relative fractions of regulatory T cells, activated NK cells, and so forth, were significantly higher in the high‐risk group. And ESTIMATE revealed the different immune scores between the two groups. Finally, six compounds were screened out as candidate therapy drugs, and the prognostic model revealed higher performance than TP53 mutation status. The prognostic signature was competent in predicting the prognosis of gastric cancer and the immune microenvironment, which could guide individualized treatment for gastric cancer in the clinic.

BackgroundA bidirectional association between atopic dermatitis and chronic kidney disease (CKD) has been revealed in observational studies, whereas the causality of this association was unclear. We conducted a Mendelian randomization study to determine the bidirectional causal association between atopic dermatitis and CKD.MethodsIndependent genetic instruments associated with atopic dermatitis and CKD at the genome-wide significance level were chosen from corresponding meta-analyses of genome-wide association studies. Summary-level data for atopic dermatitis were obtained from the EAGLE Eczema consortium (30,047 cases and 40,835 controls) and FinnGen consortium (7,024 cases and 198,740 controls). Summary-level data for CKD were derived from CKDGen consortium (64,164 cases and 625,219 controls) and FinnGen consortium (3,902 cases and 212,841 controls). The inverse-variance weighted method was used in the main analysis and supplemented with three sensitivity analyses.ResultsGenetic predisposition to atopic dermatitis was associated with an increased risk of CKD. For a one-unit increase in the prevalence of atopic dermatitis, the odds ratio of CKD was 1.07 (95% confidence interval: 1.01–1.12). In the reverse Mendelian randomization analysis, the odds ratio of atopic dermatitis was 1.14 (95% confidence interval: 1.03–1.26) for a one-unit increase in the prevalence of CKD. The associations persisted in sensitivity analyses and no pleiotropy was detected.ConclusionThis Mendelian randomization study suggests a bidirectional positive association between atopic dermatitis and CKD.

Antibiotic resistance is currently one of the greatest threats to human health. Widespread use and residues of antibiotics in humans, animals, and the environment can exert selective pressure on antibiotic resistance bacteria (ARB) and antibiotic resistance gene (ARG), accelerating the flow of antibiotic resistance. As ARG spreads to the population, the burden of antibiotic resistance in humans increases, which may have potential health effects on people. Therefore, it is critical to mitigate the spread of antibiotic resistance to humans and reduce the load of antibiotic resistance in humans. This review briefly described the information of global antibiotic consumption information and national action plans (NAPs) to combat antibiotic resistance and provided a set of feasible control strategies for the transmission of ARB and ARG to humans in three areas including (a) Reducing the colonization capacity of exogenous ARB, (b) Enhancing human colonization resistance and mitigating the horizontal gene transfer (HGT) of ARG, (c) Reversing ARB antibiotic resistance. With the hope of achieving interdisciplinary one-health prevention and control of bacterial resistance.

BackgroundOverweight and obesity are considered as one of the major risk factors for cardiovascular diseases (CVD). At present, many studies have proved that multiple nutritional supplements play an active role in metabolic diseases. However, the comparative efficacy of different nutritional supplements in improving indicators of cardiometabolic risk in obese and overweight patients is uncertain.MethodsCochrane Library, PubMed, Embase, and Web of Science were searched for the period from January 1990 to March 2022. A random-effect model was built in the Bayesian network meta-analysis. The surface under the cumulative ranking analysis (SUCRA) and clustering rank analysis was performed for ranking the effects.ResultsThe study included 65 RCTs with 4,241 patients. In terms of glucose control, probiotic was more conductive to improve FBG (MD: −0.90; 95%CrI: −1.41 to −0.38), FINS (MD: −2.05; 95%CrI: −4.27 to −0.02), HOMA-IR (MD: −2.59; 95%CI −3.42 to −1.76). Probiotic (MD: −11.15, 95%CrI −22.16 to −1.26), omega-3 (MD: −9.45; 95%CrI: −20.69 to −0.93), VD (MD: −17.86; 95%CrI: −35.53 to −0.27), and probiotic +omega-3 (MD: 5.24; 95%CrI: 0.78 to 9.63) were beneficial to the improvement of TGs, TC and HDL-C, respectively. The SUCRA revealed that probiotic might be the best intervention to reduce FBG, FINS, HOMA-IR; Simultaneously, α-lipoic acid, VD, and probiotic + omega-3 might be the best intervention to improve TGs, TC, and HDL-C, respectively. Cluster-rank results revealed probiotic had the best comprehensive improvement effect on glucose metabolism, and probiotic + omega-3 may have a better comprehensive improvement effect on lipid metabolism (cluster-rank value for FBG and FINS: 3290.50 and for TGs and HDL-C: 2117.61).ConclusionNutritional supplementation is effective on CVD risk factors in overweight and obese patients. Probiotic supplementation might be the best intervention for blood glucose control; VD, probiotic + omega-3 have a better impact on improving lipid metabolism. Further studies are required to verify the current findings.

Abstract Circular RNA (circRNA), a new type of endogenous non-coding RNA, is abundantly present in eukaryotic cells, and characterized as stable high conservation and tissue specific expression. It has been generated increasing attention because of their close association with the progress of diseases. The liver is the vital organ of humans, while it is prone to acute and chronic diseases due to the influence of multiple pathogenic factors. Moreover, hepatocellular carcinoma (HCC) is the one of most common cancer and the leading cause of cancer death worldwide. Overwhelming evidences indicate that some circRNAs are differentially expressed in liver diseases, such as, HCC, chronic hepatitis B, hepatic steatosis and hepatoblastoma tissues, etc. Additionally, these circRNAs are related to proliferation, invasion, migration, angiogenesis, apoptosis, and metastasis of cell in liver diseases and act as oncogenic agents or suppressors, and linked to clinical manifestations. In this review, we briefly summarize the biogenesis, characterization and biological functions, recent detection and identification technologies of circRNA, and regulation network mechanism of circRNA in liver diseases, and discuss their potential values as biomarkers or therapeutic targets for liver diseases, especially on HCC.

Nocturnal temperature is observed increasing with global warming. However, evidence on night-time non-optimal temperature on the risk of preterm birth (PTB) is limited, and the potential interactions with air pollution on PTB has not been well clarified. We therefore conducted a population-based retrospective cohort study to evaluate the effect of night-time temperature extremes on the risk of PTB and its interaction with air pollution. Records of 196,780 singleton births from 4 counties in Huai River Basin (2013–2018) were obtained. Gridded data on night-time temperature were collected from a high-quality Chinese Air Quality Reanalysis dataset. We used a multivariate logistic regression to evaluate the effects of night-time heat and cold exposure on the risk of PTB as well as its subtypes. Potential interactions between night-time temperature extremes and fine particulate matter

Emerging evidence suggests residential surrounding green space is beneficial for human health. The association between green space and GDM showed inconsistent results, and potential effect modification of green space with air pollution is still unclear. This study aims to evaluate the association between green space and GDM, and further explore potential interaction and medication effects. Participants were recruited from a retrospective cohort study between 2015 and 2020 in Henan, China. Residential green space based on normalized difference vegetation index (NDVI) and air pollution exposure were estimated using spatial-statistical models. Multivariate logistic regression was applied to evaluate the association between per 0.1 unit increase in NDVI with 4 buffer sizes (250 m, 500 m, 1000 m, 2000 m) and GDM. We examined potential interaction of green space and air pollutants on GDM. Mediating effects of air pollution associated with green space exposure on GDM were also investigated by causal mediation analyses. A total of 46,665 eligible pregnant women were identified. There were 4092 (8.8 %) women diagnosed with GDM according to the IADPSG criteria. We found that per 0.1-unit increment in NDVI250 m, NDVI500 m, NDVI1000 m and NDVI2000 m in second trimester were associated with the decreased risk of GDM, with adjusted OR of 0.921(95 %CI: 0.890–0.953), 0.922 (95 %CI: 0.891–0.953), 0.921 (95 %CI: 0.892–0.952) and 0.921 (95 %CI: 0.892–0.951), respectively. We identified significant interactions between second trimester PM2.5 and O3 exposure and NDVI for GDM (Pinteraction < 0.001). The causal mediation analysis showed that PM2.5 mediated approximately 2.5–5.5 % of the association between green space and GDM, while the estimated mediating effect of O3 was approximately 30.1–38.5 %. In conclusion, our study indicates that residential green space was associated with a reduced risk of GDM, particularly second trimester. Green space may benefit to GDM partly mediated by a reduction in PM2.5 and O3.

IntroductionLead (Pb) has many applications in daily life, but in recent years, various problems caused by lead exposure have aroused people’s concern. Folic acid is widely found in fruits and has received more attention for its antioxidant function. However, the role of folic acid in lead-induced kidney injury in rats is unclear. This study was designed to investigate the effects of folic acid on oxidative stress and endoplasmic reticulum stress in the kidney of rats caused by lead exposure.MethodsForty specific pathogen-free male Rattus norvegicus rats were randomly divided into control, lead, intervention, and folic acid groups. The levels of SOD, GSH-Px, GSH, and MDA were measured by biochemical kits. The protein levels of Nrf2, HO-1, CHOP, and GRP78 were measured by immunofluorescence.ResultsThis study showed that lead exposure increased the blood levels of lead in mice. However, the intervention of folic acid decreased the levels of lead, but the difference was not statistically significant. Lead exposure causes oxidative stress by decreasing kidney SOD, GSH-Px, and GSH levels and increasing MDA levels. However, folic acid alleviated the oxidative damage caused by lead exposure by increasing the levels of GSH-Px and GSH and decreasing the levels of MDA. Immunofluorescence results showed that folic acid intervention downregulated the upregulation of kidney Nrf2, HO-1, GRP78, and CHOP expression caused by lead exposure.DiscussionOverall, folic acid alleviates kidney oxidative stress induced by lead exposure by regulating Nrf2 and HO-1, while regulating CHOP and GRP78 to mitigate apoptosis caused by excessive endoplasmic reticulum stress.

Background: Existing evidence suggest that lactoferrin might be beneficial for Alzheimer’s disease, while precise mechanisms are not fully elucidated. Objective: To determine the effects of lactoferrin intervention on cognitive function from APPswe/PS1dE9 (APP/PS1) mice, and potential mechanisms involved. Design: Both the young and middle-aged male APP/PS1 mice were divided into the control and lactoferrin intervention groups with 16 weeks’ intervention. Results: Lactoferrin had no effects on cognitive function for both the young and middle-aged mice, and no key markers involved in Aβ, tau pathology, neuro-inflammation and synaptic plasticity were altered after lactoferrin intervention. With regards to gut microbiota profiles, in the young APP/PS1 mice, lactoferrin elevated the α diversity index including ACE and Chao 1, and reduced the relative abundance of the genera Bacteroides and Alistipes and elevated Oscillibacter; in addition, Oscillibacter, Anaerotruncus, EF096579_g, EU454405_g, Mollicutes_RF39, EU474361_g, EU774448_g, and EF096976_g were specifically abundant via linear discriminant analysis with effect size (LEfSe) analysis. In the middle-aged APP/PS1 mice, the relative abundance of the phylum Proteobacteria, as well as the genera Oscillospira, Coprococcus, and Ruminococcus was significantly reduced post lactoferrin; additionally, S24_7, Bacteroidia, Bacteroidetes, and Methylobacterium were specific via LEfSe analysis in the lactoferrin group. Conclusions: Dietary lactoferrin might be beneficial for gut microbiota homeostasis although it might have no effects on cognition.

Aim: We aimed to investigate factors affecting the willingness and acceptance of the SARS-CoV-2 vaccination among adults in China and sources of knowledge about the vaccine. Methods: A cross-sectional, web-based survey was conducted from September 8th to 15th, 2020, comprising of 23 questions. Binary logistic regression analysis was performed to examine factors associated with vaccination willingness and acceptance. Results: A total of 983 questionnaires were included and 81.3% of the participants were willing to receive the SARS-CoV-2 vaccine. With a “bachelor degree or above” (OR = 0.56, p = 0.020) and believing that the vaccine would not cause SARS-CoV-2 infection (OR = 0.50, p = 0.003) were associated with an increased willingness. Aged :30 years (OR = 0.38, p = 0.001), and believing that the vaccine would not cause SARS-CoV-2 infection (OR = 0.52, p = 0.004) were associated with higher acceptance; while from Henan province (OR = 2.49, p < 0.001), not willing to vaccinate (OR = 3.86, p < 0.001), not suffering from chronic diseases (OR = 2.25, p = 0.013), and thinking it was not safe and effective in preventing COVID-19 (OR = 1.94, p = 0.001) were correlated with a lower acceptance. Conclusions: In conclusion, age, education, and vaccine perception might be key factors affecting the vaccine willingness and acceptance. Triggering positive perception of vaccine, especially by targeting those aged

Background and aimsThe evidence regarding folate intake and mortality risk among patients with type 2 diabetes (T2D) remains unclear. This study aimed to investigate the association of folate intake with the risk of mortality among individuals with T2D.MethodsA total of 9,196 participants with T2D from the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 1999–2014 were included. The data of survival were obtained by the cohort database linked with the national death index up to 31 December 2015. The Cox proportional hazard model was used to evaluate the relationship between dietary folate with all-cause and cause-specific mortality.ResultsAmong patients with T2D, dietary folate intake was negatively correlated with all-cause mortality, cardiovascular mortality, and cancer mortality in men, and for women with all-cause mortality and cardiovascular mortality. The multivariate adjustment hazard ratio (HR) (95% CIs) for men of highest vs. lowest quartile was 0.77 (0.66–0.90), 0.61 (0.45–0.83), and 0.70 (0.49–0.99) for all-cause, cardiovascular, and cancer mortality, respectively. Among women, the multivariate adjustment HR (95% CIs) of highest vs. lowest quartile was 0.77 (0.64–0.92), 0.52 (0.33–0.83), and 0.78 (0.50–1.22) for all-cause, cardiovascular, and cancer mortality, respectively.ConclusionHigher dietary intake of folate was significantly associated with lower all-cause and cardiovascular mortality. This cohort study suggested that increasing the dietary folate intake may reduce mortality risk among U.S. adults with T2D.

The way that males and females react to environmental exposures and negative impacts on their neurological systems is often different. Although previous research has examined the cognitively impairing effects of solitary metal exposures, the relationship between metal mixtures and cognitive function, particularly when considering an individual’s sex, remains elusive. This study aimed to investigate the sex differences in the association between multiple metal combinations and cognitive function in older Americans. This research employed the 2011–2014 NHANES survey of elderly Americans. The association between five mixed metals and four cognitive tests (the animal fluency test (AFT), the digit symbol substitution test (DSST), the instant recall test (IRT), and the delayed recall test (DRT)) were investigated with generalized linear regression model (GLM), Bayesian kernel machine regression model (BKMR), weighted quantile sum regression model (WQS), and quantile g-computation regression model (Qgcomp). A total of 1833 people, including 883 males and 950 females, enrolled in this cross-sectional study. We discovered that blood lead and blood cadmium were negatively associated with cognitive performance, while blood selenium demonstrated a positive association with cognitive function in older people. The negative relationship of heavy metal combinations on cognitive function might be somewhat reduced or even reversed via selenium. The IRT, AFT, and DSST are three of the four cognitive tests where men had more dramatic positive or negative results. There was a sex-specific connection between blood metal ratios and cognitive function among older Americans, as evidenced by the more significant relationship between mixed metals and cognitive performance in men (either positively or negatively). These results emphasize the impacts of ambient heavy metal exposure on cognitive function by employing sex-specific methods.

Naringin (Nar) is a dihydroflavonoid compound, widely found in citrus fruit and used in Chinese herbal medicine. As a phytochemical, it acts as a dietary supplement that can delay aging and prevent aging-related disease, such as obesity and diabetes. However, its exact mechanism remains unclear. In this study, the high-glucose-induced (HGI) Caenorhabditis elegans model was used to evaluate the anti-aging and anti-obesity effects of Nar. The mean lifespan and fast movement span of HGI worms were extended roughly 24% and 11%, respectively, by Nar treatment. Oil red O staining revealed a significant reduction in fat accumulation and dFP::LGG-labeled worms showed the promotion of autophagy. Additionally, whole transcriptome sequencing and gene set variation analysis suggested that Nar upregulated the lipid biosynthesis and metabolism pathways, as well as the TGF-β, Wnt and longevity signaling pathways. Protein–protein interaction (PPI) network analysis identified hub genes in these pathways for further analysis. Mutant worms and RNA interference were used to study mechanisms; the suppression of hlh-30, lgg-1, unc-51, pha-4, skn-1 and yap-1 disabled the fat-lowering, lifespan-prolonging, and health-promoting properties of Nar. Collectively, our findings indicate that Nar plays an important role in alleviating HGI-aging and anti-obesity effects by reducing fat accumulation and promoting autophagy.

ObjectiveWhether fasting insulin (FI) plays a role in cancer risk remains unclear. This study aimed to investigate the association between FI and cancer risk and to explore its potential mediator role in the association between type 2 diabetes mellitus (T2DM) and cancer.MethodsTwo-sample Mendelian randomization (TSMR) analysis was performed to evaluate the effect of FI on overall and 14 site-specific cancers using genome-wide association study (GWAS) summary-level data from Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) and consortia of 14 site-specific cancers. The primary MR approach was conducted by using the random-effect inverse-variance weighted (IVW) method, and sensitivity analyses were implemented by adopting weighted-median, weighted-mode, MR-Egger, and MR-PRESSO tests. Polygenic risk score analysis was executed by using individual-level data from UK Biobank to validate the findings from TSMR analyses. Multivariable Mendelian randomization (MVMR) was carried out to estimate the mediation effect of FI on the association between T2DM and cancer.ResultsTSMR study suggested that genetically determined high FI levels were associated with increased risk of colorectal cancer (odds ratio (OR) = 1.87, 95% CI: 1.23–2.84, p = 0.003) and endometrial cancer (OR = 1.89, 95% CI: 1.08–3.01, p = 0.008), but not associated with overall cancer risk or the other 12 studied cancer sites. Polygenic risk score analysis successfully replicated the association between genetic liability to high FI levels and the increased risk of colorectal and endometrial cancers. MVMR and MR mediation analyses detected an intermediary effect of FI and quantified that FI mediated 21.3% of the association between T2DM and endometrial cancer.ConclusionsThis study demonstrated that FI levels are associated with the risk of colorectal and endometrial cancers, and FI was found to play an intermediary role in the association between T2DM and endometrial cancer. The associations between FI and other cancers need to be further studied.

Background: Association between ambient air pollution and congenital heart diseases (CHDs) remains inconclusive, and the critical exposure windows has not been well studied. Objectives: This case-control study aimed to assess the effect of ambient air pollution exposure on the risk of CHDs and the subtypes in Henan, China, and further to explore potential susceptible windows. Methods: Daily average particulate matter with an aerodynamic diameter of ≤2.5 µm (PM2.5) and ≤10 µm (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO) and ozone (O3) were collected by Chinese Air Quality Reanalysis datasets. Binary logistic regression was used to examine trimester-specific associations between per 10 μg/m3 increase in air pollutants and CHDs as well as the major subtypes. Distributed lag models incorporating logistic regression were applied to explore weekly-specific associations. Results: A total of 196,069 singleton live births were included during 2013–2018, 643 CHDs were identified (3.3‰). We found that first and second trimester CO exposure increased overall CHDs risk, the adjusted odds ratio (aOR) and 95% confidence interval (CI) were 1.066 (1.010–1.125) and 1.065 (1.012–1.122). For CHDs subtypes, we observed that NO2 and CO in first trimester, PM2.5 and PM10 in the second trimester exposure were associated with the risk of atrial septal defect (ASD), the susceptible windows of air pollutants and ASD mainly occurred in the 1st- 6th gestational weeks. No positive association was observed for air pollution and tetralogy of Fallot. Conclusion: Our findings suggest that ambient air pollution exposure is associated with the risk of CHDs especially for ASD, and the susceptible windows generally occurred in first trimester. Further well-designed longitudinal studies are warranted to confirm our findings.

Juglone (JUG), a natural product found in walnut trees and other plants, shows potent antioxidant, antimicrobial, and immunoregulatory activities. However, it remains unknown whether JUG can alleviate ulcerative colitis. This study aims to explore the effect of JUG on dextran sulfate sodium (DSS)-induced colitis in mice. The mice were randomly assigned into three groups: the vehicle group, the DSS group, and the JUG group. The experiments lasted for 17 days; during the experiment, all mice received dimethyl sulfoxide (DMSO, 0.03% v/v)-containing water, while the mice in the JUG group received DMSO-containing water supplemented with JUG (0.04 w/v). Colitis was induced by administering DSS (3% w/v) orally for 10 consecutive days. The results showed that the JUG treatment significantly ameliorated body weight loss and disease activity index and improved the survival probability, colon length, and tissue damage. JUG reversed the DSS-induced up-regulation of proinflammatory cytokines, including interleukin (IL)-6, 12, 21, and 23, and tumor necrosis factor-alpha, and anti-inflammatory cytokines, such as IL-10 and transforming growth factor-beta, in the serum of the colitis mice. Additionally, the activation of mitochondrial uncoupling protein 2 and phospho-Nuclear Factor-kappa B p65 and the inhibition of the kelch-like ECH-associated protein 1 and NF-E2-related factor 2 induced by DSS were also reversed under JUG administration. Although the JUG group possessed a similar microbial community structure as the DSS group, JUG enriched potential beneficial microbes such as Lachnospiraceae_NK4A136_group but not pathogens such as Escherichia Shigella, which was dominative in DSS group, at the genus level. In conclusion, our results demonstrated that JUG could be a promising agent for UC prevention to regulate inflammatory cytokines and oxidative stress.

Previous observational studies have shown that exposure to ambient temperature and air pollution were associated with the incidence of gestational diabetes mellitus (GDM). However, the susceptible time window of non-optimal temperature on GDM is still unknown, and the interaction with air pollution has not been examined. We conducted a prospective cohort study in Guangzhou, China to investigate the windows of susceptibility of temperature extremes and variability on the risk of GDM and to explore any interaction effect with air pollution. Daily maximum (Tmax), minimum temperature (Tmin) and diurnal temperature range (DTR) were obtained from Guangdong Meteorological Service. Distributed lag non-linear models with a logistic regression were applied to assess the effect of temperature extremes and DTR in different weeks of gestation on GDM. To examine the interaction effect, relative excess risk due to interaction index, attributable proportion and synergy index were calculated. There were 5,165 pregnant women enrolled, of which 604 were diagnosed with GDM (11.7%). Compared with a reference temperature (50th percentile of Tmax), we found that extreme high temperature (99th percentile of Tmax) exposure during 21st and 22nd gestational weeks was associated with an increased risk of GDM. Extreme low temperature (1st percentile of Tmax) exposure during 14th to 17th weeks increased the risk of GDM. We observed that per 1 °C increment of DTR during 21st to 24th weeks was associated with an elevated GDM risk. No interaction effect of temperature extremes or variability with air pollution on GDM were observed. Our results suggested that non-optimal temperature is an independent risk factor of GDM. The time window of susceptibility for extreme temperatures and DTR exposure on the risk of GDM generally occurred in second trimester of pregnancy. In the context of climate change, our study has important implications for reproductive health and justifies more research in different climate zones.

The evidence regarding the intake of dietary folate, vitamin B6, and vitamin B12 in relation to mortality in the general population is limited. This study aimed to examine the relationship between dietary intakes of folate, vitamin B6, and vitamin B12 in relation to all-cause and cause-specific mortality in a large U.S. cohort. This study included a total of 55,569 adults from the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 1999–2014. Vital data were determined by linking with the National Death Index records through 31 December 2015. Cox proportional hazards models were used to investigate the relationships of all-cause and cause-specific mortality with dietary folate, vitamin B6, and vitamin B12 intake. Dietary intakes of folate and vitamin B6 were inversely associated with mortality from all-cause, cardiovascular disease, and cancer for men and with mortality from all-cause and cardiovascular disease for women. In men, the multivariable hazard ratios (95% confidence intervals) for the highest versus lowest quintiles of folate and vitamin B6 were 0.77 (0.71–0.85) and 0.79 (0.71–0.86) for all-cause mortality, 0.59 (0.48–0.72) and 0.69 (0.56–0.85) for CVD mortality, and 0.68 (0.56–0.84) and 0.73 (0.60–0.90) for cancer mortality, respectively. Among women, the multivariable hazard ratios (95% confidence intervals) for the highest versus lowest quintiles of folate and vitamin B6 were 0.86 (0.78–0.95) and 0.88 (0.80–0.97) for all-cause mortality and 0.53 (0.41–0.69) and 0.56 (0.44–0.73) for CVD mortality, respectively. No significant associations between dietary vitamin B12 and all-cause and cause-specific mortality were observed. In conclusion, higher dietary intakes of folate and vitamin B6 were significantly associated with lower all-cause and cardiovascular mortality. Our findings suggest that increasing the intake of folate and vitamin B6 may lower the mortality risk among U.S. adults.

Background: There is no study that has systematically investigated the breadth and validity of the associations of folate and multiple health outcomes. We aimed to evaluate the quantity, validity, and credibility of evidence regarding associations between folate and multiple health outcomes by using umbrella review of meta-analysis.Methods: We searched the MEDLINE, EMBASE, and Cochrane Library databases from inception to May 20, 2018, to identify potential meta-analyses that examined the association of folate with any health outcome. For each included meta-analysis, we estimated the summary effect size and their 95% confidence interval using the DerSimonian and Laird random-effects model. We used the AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews) to assess methodological quality and the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation working group classification) to assess the quality of evidence for each outcome included in the umbrella review.Results: Overall, 108 articles reporting 133 meta-analyses of observational studies and 154 meta-analyses of randomized controlled trials (RCTs) were included in the study. Among them, 108 unique exposure–outcome–population triplets (referred to as unique meta-analyses hereafter) of RCTs and 87 unique meta-analyses of observational studies were reanalyzed. Beneficial effects of folate were observed in the all-cause mortality rate and in a number of chronic diseases, including several birth/pregnancy outcomes, several cancers, cardiovascular disease and metabolic-related outcomes, neurological conditions, and several other diseases. However, adverse effects of folate were observed for prostate cancer, colorectal adenomatous lesions, asthma or wheezing, and wheezing as an isolated symptom and depression.Conclusions: Current evidence allows for the conclusion that folate is associated with decreased risk of all-cause mortality and a wide range of chronic diseases. However, folate may be associated with an increased risk of prostate cancer. Further research is warranted to improve the certainty of the estimates.

Fewer studies have focused on the independent association between mean corpuscular volume (MCV) and cognitive performance. This study was designed to characterize the cross-sectional association between MCV and cognitive performance in a large sample of Chinese residents (age≥45 years) from the China Health and Retirement Longitudinal Study (CHARLS). A total of 4023 male and 4173 female adults with MCV ≥ 80 fl were included for analysis. By multivariable linear regression analysis, for the total subjects, MCV level was significantly negatively associated with global cognitive function and episodic memory. When adjusted by sex, only in male subjects, higher MCV level was associated with reduced scores for global cognitive function, episodic memory and mental status. Via binary logistic regression analysis, the higher MCV level (MCV>100 fl) was associated with poor global cognitive function (OR = 1.601; 95% CI = 1.198-2.139; p = 0.001), episodic memory (OR = 1.679; 95% CI = 1.281-2.201; p

Background: Even though it is well-known that iron deficiency is the result of chronic kidney disease (CKD), whether iron will affect kidney function and disease in the general population is not clear. We thus conducted a nationwide cross-sectional study using data from the China Health and Nutrition Survey (CHNS) to assess the relationship of iron status with estimated glomerular filtration rate (eGFR) and CKD among general adults.Methods: A total of 8,339 adults from the China Health and Nutrition Survey in the wave of 2009 were included to assess the association between iron status and eGFR/CKD. Serum ferritin (SF), transferrin, soluble transferrin receptor (sTfR), and hemoglobin (Hb) were measured. The relationship of iron status and eGFR was evaluated by using multi-variable linear regression model. The effect of iron status on the odds of CKD was calculated by logistic regression model.Results: For the association between iron status and eGFR, every 100 μg/L increase in SF was correlated with 0.26 ml/min per 1.73 m2 (95% CI: 0.08–0.44) decrease in eGFR, and every 5 mg/L increase in sTfR was associated with a decrease of 6.00 ml/min per 1.73 m2 (95% CI: 3.79–8.21) in eGFR. There were no significant associations between Hb or transferrin with eGFR. For the association between iron status and CKD, every 5 g/L increase in sTfR was associated with an odds ratio of 3.72 (95% CI: 2.16–6.13) for CKD. The concentrations of Hb were associated with the odds of CKD in a U-shaped manner, with the lowest risk in the Hb range of 136–141 g/L. There was a positive correlation between SF concentration and CKD prevalence but not in a dose–response manner. The odds of CKD for participants in the highest tertile increased by 28% (98% CI: 1–63%) compared with those in the lowest tertile.Conclusion: The concentration of SF and sTfR was positively correlated with the odds of CKD, and Hb was associated with the odds of CKD in a U-shaped manner. Further large prospective researches are warranted to confirm these findings.

Background Obesity-induced glucose metabolism disorder is associated with chronic, low-grade, systemic inflammation and is considered a risk factor for diabetes and metabolic syndrome. Resveratrol (RES), a natural anti-inflammatory compound, is observed to improve glucose tolerance and insulin sensitivity in obese rodents and humans. This study aimed to test the effects of RES administration on insulin signaling and the inflammatory response in visceral white adipose tissue (WAT) caused by a high-fat diet (HFD) in mice. Methods A total of 40 wild-type C57BL/6 male mice were divided into four groups (10 in each group): the standard chow diet (STD) group was fed a STD; the HFD group was fed a HFD; and the HFD-RES/L and HFD-RES/H groups were fed a HFD plus RES (200 and 400 mg/kg/day, respectively). The L and H in RES/L and RES/H stand for low and high, respectively. Glucose tolerance, insulin sensitivity, circulating inflammatory biomarkers and lipid profile were determined. Quantitative PCR and Western blot were used to determine the expression of CC-chemokine receptor 2 (CCR2), other inflammation markers, glucose transporter 4 (GLUT4), insulin receptor substrate 1 (IRS-1) and pAkt/Akt and to assess targets of interest involving glucose metabolism and inflammation in visceral WAT. Results HFD increased the levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol and proinflammatory cytokines in serum, decreased the high-density lipoprotein cholesterol level in serum, and induced insulin resistance and WAT inflammation in mice. However, RES treatment alleviated insulin resistance, increased the expressions of pAkt, GLUT4 and IRS-1 in WAT, and decreased serum proinflammatory cytokine levels, macrophage infiltration and CCR2 expression in WAT. Conclusion Our results indicated that WAT CCR2 may play a vital role in macrophage infiltration and the inflammatory response during the development of insulin resistance in HFD-induced obesity. These data suggested that administration of RES offers protection against abnormal glucose metabolism and inflammatory adaptations in visceral WAT in mice with HFD-induced obesity.

Background The methylenetetrahydrofolate reductase (MTHFR) is thought to be involved in the development of nonsyndromic cleft lip with or without cleft palate (NSCL/P). However, conflicting results have been obtained when evaluating the association between maternal MTHFR C677T and A1298C polymorphisms and the risk of NSCL/P. In light of this gap, a meta-analysis of all eligible case-control studies was conducted in the present study. Materials and Methods A total of 15 case-control studies were ultimately identified after a comprehensive literature search and Hardy-Weinberg equilibrium (HWE) examination. Cochrane’s Q test and index of heterogeneity (I2) indicated no obvious heterogeneity among studies. Results Fixed or random-effects models were used to calculate the pooled odds ratios (ORs). The results showed that the TT genotype in mothers increased the likelihood of having NSCL/P offspring 1.25 times (95% CI: 1.047-1.494) more than the CC homozygotes. Meanwhile, maternal TT genotype increased the risk of producing NSCL/P offspring in recessive model (OR=1.325, 95% CI: 1.124-1.562). However, the CT heterozygote and the CT+TT dominant models had no association with NSCL/P offspring compared with the CC wild-type homozygote model. Subgroup analyses based on ethnicity indicated that maternal TT genotype increased the likelihood of having NSCL/P offspring in Whites (OR=1.308, 95% CI: 1.059-1.617) and Asians (OR=1.726, 95% CI: 1.090-2.733) in recessive model. Also, subgroup analyses based on source of control showed that mothers with the 677TT genotype had a significantly increased susceptibility of having NSCL/P children in hospital based population (HB) when compared with CC homozygotes (OR=1.248, 95% CI: 1.024-1.520) and un- der the recessive model (OR=1.324, 95% CI: 1.104-1.588). Furthermore, maternal A1298C polymorphism had no significant association with producing NSCL/P offspring (dominant model OR=0.952, 95% CI: 0.816-1.111, recessive model OR=0.766, 95% CI: 0.567-1.036). Conclusion MTHFR C677T polymorphism is associated with the risk of generating NSCL/P offspring, and being a 677TT homozygote is a risk factor. MTHFR A1298C polymorphism was not associated with generating NSCL/P offspring. However, further work should be performed to confirm these findings.

Dioxin-related compounds are associated with teratogenic and mutagenic risks in laboratory animals, and result in adverse pregnancy outcomes. However, there were inconsistent results in epidemiology studies. In view of this difference, we conducted a systematic review and meta-analysis to examine this association and to assess the heterogeneity among studies. Comprehensive literature searches were performed to search for relevant articles published in English up to 15 May 2012. In total, we identified 15 studies which included 9 cohort and 6 case control studies. The Cochrane Q test and index of heterogeneity (I2) were used to evaluate heterogeneity. In either cohort studies (I2=0.89, p < 0.0001) or case control studies (I2=0.69, p=0.02), significant heterogeneity of risk estimates were observed. Subgroup analyses found no significant increased risk of adverse pregnancy outcome with air dioxin-related compounds exposure (RR=0.99, 95% CI:0.85–1.16), no significant increased risk of spontaneous abortion (SAB) with exposure to food dioxin-related compounds (RR=1.05, 95% CI:0.80–1.37), higher significant risks of low birth weight (LBW) with exposure to food dioxin-related compounds (RR=1.55, 95% CI:1.24–1.94), and higher significant risks of birth defects with maternal solid contaminants dioxin exposure (OR=1.24, 95% CI:1.19–1.29). In conclusion, more evidences are needed to confirm the association between environmental dioxin-related compounds exposure and pregnancy outcome.

Oxidative skeletal muscles are more resistant than glycolytic muscles to cachexia caused by chronic heart failure and other chronic diseases. The molecular mechanism for the protection associated with oxidative phenotype remains elusive. We hypothesized that differences in reactive oxygen species (ROS) and nitric oxide (NO) determine the fiber type susceptibility. Here, we show that intraperitoneal injection of endotoxin (lipopolysaccharide, LPS) in mice resulted in higher level of ROS and greater expression of muscle-specific E3 ubiqitin ligases, muscle atrophy F-box (MAFbx)/atrogin-1 and muscle RING finger-1 (MuRF1), in glycolytic white vastus lateralis muscle than in oxidative soleus muscle. By contrast, NO production, inducible NO synthase (iNos) and antioxidant gene expression were greatly enhanced in oxidative, but not in glycolytic muscles, suggesting that NO mediates protection against muscle wasting. NO donors enhanced iNos and antioxidant gene expression and blocked cytokine/endotoxin-induced MAFbx/atrogin-1 expression in cultured myoblasts and in skeletal muscle in vivo. Our studies reveal a novel protective mechanism in oxidative myofibers mediated by enhanced iNos and antioxidant gene expression and suggest a significant value of enhanced NO signaling as a new therapeutic strategy for cachexia.