Alteration in gut microbiota is associated with immune imbalance in Graves' disease.

Background: Graves' disease (GD), characterized by immune aberration, is associated with gut dysbiosis. Despite the growing interest, substantial evidence detailing the precise impact of gut microbiota on GD's autoimmune processes remains exceedingly rare. Objective: This study was designed to investigate the influence of gut microbiota on immune dysregulation in GD. Methods: It encompassed 52 GD patients and 45 healthy controls (HCs), employing flow cytometry and enzyme-linked immunosorbent assay to examine lymphocyte and cytokine profiles, alongside lipopolysaccharide (LPS) levels. Gut microbiota profiles and metabolic features were assessed using 16S rRNA gene sequencing and targeted metabolomics. Results: Our observations revealed a disturbed B-cell distribution and elevated LPS and pro-inflammatory cytokines in GD patients compared to HCs. Significant differences in gut microbiota composition and a marked deficit in short-chain fatty acid (SCFA)-producing bacteria, including ASV263(Bacteroides), ASV1451(Dialister), and ASV503(Coprococcus), were observed in GD patients. These specific bacteria and SCFAs showed correlations with thyroid autoantibodies, B-cell subsets, and cytokine levels. In vitro studies further showed that LPS notably caused B-cell subsets imbalance, reducing conventional memory B cells while increasing naïve B cells. Additionally, acetate combined with propionate and butyrate showcased immunoregulatory functions, diminishing cytokine production in LPS-stimulated cells. Conclusion: Overall, our results highlight the role of gut dysbiosis in contributing to immune dysregulation in GD by affecting lymphocyte status and cytokine production.

Eukaryotes may play an important ecological role in the gut microbiome of Graves' disease.

The prevalence of autoimmune diseases worldwide has risen rapidly over the past few decades. Increasing evidence has linked gut dysbiosis to the onset of various autoimmune diseases. Thanks to the significant advancements in high-throughput sequencing technology, the number of gut microbiome studies has increased. However, they have primarily focused on bacteria, so our understanding of the role and significance of eukaryotic microbes in the human gut microbial ecosystem remains quite limited. Here, we selected Graves' disease (GD) as an autoimmune disease model and investigated the gut multi-kingdom (bacteria, fungi, and protists) microbial communities from the health control, diseased, and medication-treated recovered patients. The results showed that physiological changes in GD increased homogenizing dispersal processes for bacterial community assembly and increased homogeneous selection processes for eukaryotic community assembly. The recovered patients vs. healthy controls had similar bacterial and protistan, but not fungal, community assembly processes. Additionally, eukaryotes (fungi and protists) may play a more significant role in gut ecosystem functions than bacteria. Overall, this study gives brief insights into the potential contributions of eukaryotes to gut and immune homeostasis in humans and their potential influence in relation to therapeutic interventions.

Microbial Mechanistic Insight into the Role of Yeast-Derived Postbiotics in Improving Sow Reproductive Performance in Late Gestation and Lactation Sows.

The purpose of this study is to investigate the effects of supplementing Yeast-derived postbiotics (Y-dP) to the diet of sows during late pregnancy and lactation on fecal microbiota and short-chain fatty acids (SCFA) in sows and their offspring weaned piglets, as well as the relationship between gut microbiota and SCFA, serum cytokines, and sow reproductive performance. A total of 150 sows were divided into three groups: control diet (CON), CON + Y-dP 1.25 g/kg, and CON + Y-dP 2 g/kg. The results showed that supplementing 0.125% Y-dP to the diet of sows can increase the content of isobutyric acid (IBA) in the feces of pregnant sows and reduce the content of butyric acid (BA) in the feces of weaned piglets (p < 0.05). The fecal microbiota of pregnant sows ß diversity reduced and piglet fecal microbiota ß diversity increased (p < 0.05). Y-dP significantly increased the abundance of Actinobacteria and Limosilactobacilli in the feces of pregnant sows (p < 0.05), as well as the abundance of Verrucomicrobiota, Bacteroidota, and Fusobacteriota in the feces of piglets (p < 0.05). The abundance of Bacteroidota in the feces of pregnant sows is positively correlated with propionic acid (PA) (r > 0.5, p < 0.05). The abundance of Prevotellaceae_NK3B31_group was positively correlated with Acetic acid (AA), PA, Valerate acid (VA), and total volatile fatty acid (TVFA) in the feces of pregnant sows (r > 0.5, p < 0.05), and Bacteroidota and Prevotellaceae_NK3B31_group were negatively correlated with the number of stillbirths (r < -0.5, p < 0.05). The abundance of Lactobacillus and Holdemanella in piglet feces was positively correlated with TVFA in feces and negatively correlated with IgA in serum (r > 0.5, p < 0.05). In conclusion, supplementing Y-dP to the diet of sows from late gestation to lactation can increase the chao1 index and α diversity of fecal microorganisms in sows during lactation, increase the abundance of Actinobacteria and Limosilactobacilli in the feces of sows during pregnancy, and increase the abundance of beneficial bacteria such as Bacteroidetes in piglet feces, thereby improving intestinal health. These findings provide a reference for the application of Y-dP in sow production and a theoretical basis for Y-dP to improve sow production performance.

Generation of Porcine Angiogenin 4-Expressing Pichia pastoris and Its Protection against Intestinal Inflammatory Injury.

Antimicrobial peptides have been extensively studied as potential alternatives to antibiotics. Porcine angiogenin 4 (pANG4) is a novel antimicrobial peptide in the angiogenin (ANG) family, which may have a regulatory effect on intestinal microflora. The object of present study is obtained pANG4 protein by heterologous expression, so as to explore the biological function of recombinant pANG4 (rpANG4). The pANG4 was expressed in Pichia pastoris (P. pastoris) and anti-inflammatory effects were investigated in intestinal porcine epithelial cell line-J2 (IPEC-J2) and mice. Purified rpANG4 had bacteriostatic activity and did not cause hemolysis or cytotoxicity at concentrations below 128 µg/mL. Purified rpANG4 increased the activity of IPEC-J2 and reduced apoptosis in vitro. rpANG4 reduced the pro-inflammatory gene expression and upregulated tight junction protein gene expression during inflammation. rpANG4 alleviated lipopolysaccharide (LPS)-induced liver and spleen damage, intestinal inflammation, jejunal apoptosis genes' expression, and improved immune function in an in vivo mice model. rpANG4 increased tight junction protein gene expression in jejunum, thereby improving the jejunum intestinal barrier function. In conclusion, rpANG4 had antibacterial activity, inhibited intestinal inflammation, improved intestinal barrier function, and alleviated liver and spleen damage. The current study contributes to the development of antibiotic substitutes and the improvement of animal health.

Dual-network hydrogels based on dynamic imine and borate ester bonds with antibacterial and self-healing properties.

Polymeric hydrogel materials with multiple functions are in great demand in practical biomedical scenarios. In this work, a self-healing hydrogel with both antimicrobial properties was prepared using a strategy that combines dynamic imine and borate ester bonds. In this hydrogel, polyvinyl alcohol (PVA) is used as the base network, and borax solution as the cross-linking agent, and borate ester bonds can be formed between these two. Dialdehyde carboxymethyl cellulose (DCMC) was selected to cross-link with the amino groups in carboxymethyl chitosan (CMCS) and polyethyleneimine (PEI) to form dynamic imine bonds. The PVA/PEI/DCMC/CMCS hydrogels prepared by double chemical cross-linking have good mechanical properties (maximum tensile strength up to 289 KPa and strain at the break up to 1025%). Due to the uniqueness of the two chemical bonds, the hydrogel material is self-healing at room temperature without additional stimulation. In addition, the inherent antibacterial properties of the raw materials in this hydrogel confer antibacterial properties, with a kill rate of up to 99% against E. coli and S. aureus. The multifunctional hydrogels developed in this study provide more ideas and references for the future application of hydrogel materials in practical scenarios.

Yeast culture supplementation of sow diets regulates the immune performance of their weaned piglets under lipopolysaccharide stress.

The aim of this study was to investigate the effect of dietary supplementation of sows with yeast cultures (XPC) during late gestation and lactation on the immune performance of their weaned offspring under lipopolysaccharide (LPS) stress. A total of 40 Landrace × Yorkshire sows (parity 3 to 7) with similar backfat thickness were selected and randomly divided into two treatment groups: a control group (basal diet) and a yeast culture group (basal diet + 2.0 g/kg XPC). The trial was conducted from day 90 of gestation to day 21 of lactation. At the end of the experiment, 12 piglets with similar weights were selected from each group and slaughtered 4 h after intraperitoneal injection with either saline or LPS. The results showed that the concentrations of interleukin-6 (IL-6) in the thymus and tumor necrosis factor-α in the liver increased significantly (P < 0.05) in weaned piglets after LPS injection. Maternal dietary supplementation with XPC significantly reduced the concentration of inflammatory factors in the plasma and thymus of weaned piglets (P < 0.05). LPS injection significantly upregulated the expression of some tissue inflammation-related genes, significantly downregulated the expression of intestinal tight junction-related genes, and significantly elevated the protein expression of liver phospho-nuclear factor kappa B (p-NF-κB), the phospho-inhibitory subunit of NF-κB (p-IκBα), phospho-c-Jun N-terminal kinase (p-JNK), Nuclear factor kappa-B (NF-κB), and the inhibitory subunit of NF-κB (IκBα) in weaned piglets (P < 0.05). Maternal dietary supplementation with XPC significantly downregulated the gene expression of IL-6 and interleukin-10 (IL-10) in the thymus and decreased the protein expression of c-Jun N-terminal kinase (JNK) in the liver of weaned piglets (P < 0.05). In summary, injection of LPS induced an inflammatory response in weaned piglets and destroyed the intestinal barrier. Maternal dietary supplementation of XPC improved the immune performance of weaned piglets by inhibiting inflammatory responses.

Weaning older, more mature pigs helps prevent many of the adverse gastrointestinal effects associated with weaning stress, and maternal nutritional interventions can influence offspring gut health and growth performance. Therefore, it is important to explore the effects of maternal nutritional interventions on their offspring. Yeast cultures are a class of biological products consisting of metabolites produced during the anaerobic fermentation of yeast and some live yeast cells, and function to maintain the intestinal health of animals and improve production performance. The effect of sow dietary supplementation with yeast cultures on the immune performance of their weaned offspring under lipopolysaccharide stress has not so far been reported. This study provided a basis for understanding the effects of maternal transfer of yeast cultures to their offspring and provided data to support the application of yeast cultures in actual production.

Effects of yeast-derived postbiotic supplementation in late gestation and lactation diets on performance, milk quality, and immune function in lactating sows.

This experiment was conducted to determine the effects of yeast-derived postbiotic (YDP) supplementation in sow diets during late gestation and lactation on the performance of sows and their offspring. At 90-d gestation, 150 sows (Landrace × Large White, parity: 3.93 ±â€…0.11) were allocated to three dietary treatments (n = 50 per treatment): 1) basal diet (control [CON]), 2) basal diet with 1.25 g/kg YDP (0.125 group), and 3) basal diet with 2.00 g/kg YDP (0.200 group). The experiment continued until the end of weaning (day 21 of lactation). Supplementation with YDP resulted in greater deposition of backfat in sows during late gestation and an increasing trend in average weaning weight of piglets than observed in the CON group (P < 0.01, P = 0.05). Supplementation with YDP decreased piglet mortality and diarrhea index in piglets (P < 0.05). In farrowing sows' serum, the glutathione peroxide content in the YDP group was lower than that in the CON group (P < 0.05); the content of immunoglobulin A (IgA) in the 0.200 group or YDP group was higher than that in the CON group (P < 0.05). In lactating sows' serum, malondialdehyde content was higher in the YDP group (P < 0.05). In day 3 milk of sows, the 0.200 group tended to increase the lactose content (P = 0.07), and tended to decrease the secretory immunoglobulin A (sIgA) content (P = 0.06) with respect to that in the CON group. The sIgA content in the YDP group was lower than that in the CON group (P < 0.05). In the milk of sows, the 0.200 group tended to increase the lactose content with respect to that in the CON group (P = 0.08); the immunoglobulin G (IgG) content in the 0.125 group or YDP group was higher than that in the CON group (P < 0.05). YDP supplementation increased the IgA content in the milk (P < 0.01). In sow placenta, the content of total anti-oxidant capacity in the YDP group was higher than that in the CON group (P = 0.05); and the content of transforming growth factor-ß in the YDP group was higher than that in the CON group (P < 0.05). In piglet serum, the content of IgG and immunoglobulin M in the 0.125 group was higher than that in the CON and 0.200 groups (P < 0.05). In summary, this study indicated that feeding sows diets supplemented with YDP from late gestation through lactation increased sows' backfat deposition in late gestation and piglets' weaning weight; decreased piglet mortality and diarrhea index in piglets; and improved maternal and offspring immunity.

Rapid fetal and reproductive tissue development in late gestation poses a challenge to sow health. Nutritional interventions have been shown to effectively improve animal performance. The present study investigated whether dietary supplementation with a yeast-derived postbiotic (YDP) during late gestation and lactation might improve the health and production performance of sows and piglets. At two tested dose levels (1.25 and 2.00 g/kg in the diet), dietary YDP supplementation increased backfat deposition in sows during late gestation and weaning weight in piglets, and decreased the diarrhea index in piglets. YDP supplementation tended to increase lactose content in sow milk. Dietary YDP supplementation improved immunity in sows at farrowing and piglets at weaning. These findings indicated that YDP use improves sows' production performance and may serve as an important approach to optimizing nutrient programs in sow production.

Silibinin Alleviates Lipopolysaccharide Induced Inflammation in Porcine Mammary Epithelial Cells via mTOR/NF-κB Signaling Pathway.

SCOPE: Inflammatory responses reduce milk production in lactating sow. Silymarin (Silibinin is main component) reduces the inflammatory reaction and increases milk yield in lactating sow in the previous study. In the present study, silibinin may be a previously unrecognized nutrients in inflammatory resolution in porcine mammary epithelial cells (PMECs) is hypothesized. METHODS AND RESULTS: PMECs are treated with or without lipopolysaccharide (LPS) in the absence or presence of silibinin to test cell viability, cell cycle, cell apoptosis, cellular inflammatory factors, and signaling protein phosphorylation and expression. Silibinin promotes the proliferation of PMEC independent of the estrogen pathway. In LPS-induced damage of PMECs, silibinin protects cell proliferation, as well as reduced cell apoptosis. Silibinin reverses the LPS-induced increase in tumor necrosis factor-alpha (TNF-α) expression compared with control. In addition, silibinin accentuates the LPS-induced decrease in the key proteins phosphorylated-ribosomal protein S6 (p-S6) and phosphorylated-mammalian target of rapamycin (p-mTOR) of the mammalian target of rapamycin (mTOR) signaling pathway. Furthermore, silibinin reverses the increase in phosphorylated-nuclear factor-kappa B p65 (p-NF-κB p65), phosphorylated-Ikappab-alpha (p-IκB-α), and phosphorylated-Mitogen-activated protein kinase p38 (p-MAPK p38) expression in LPS-induced damage in PMECs. CONCLUSION: This study highlights silibinin-mTOR/NF-κB axis plays an important role in the control of inflammation in PMECs, and suggests that silibinin may be an effective dietary strategy to alleviate the inflammatory response in lactating sow.

Polyvinyl alcohol/carboxymethyl chitosan hydrogel loaded with silver nanoparticles exhibited antibacterial and self-healing properties.

Hydrogel materials are gradually increasing research in biological aspects due to their unique properties. In order to prepare hydrogels with the potential to be used in clinical wound therapy, the authors prepared a bifunctional hydrogel with antibacterial and self-healing properties. The hydrogel was composed of borax cross-linked polyvinyl alcohol (PVA) and carboxymethyl chitosan (CMCS), which realizes self-healing between polymers through hydrogen bonds and borate ester bonds. The double cross-linking of hydrogen bonds and borate ester bonds also endows the hydrogel with better mechanical properties (toughness and tensile stress can reach 22.30 MJ/m3 and 70.35 KPa, respectively). On this basis, adding highly stable silver nanoparticles (AgNPs) to the hydrogel can effectively inhibit the growth of E. coli and S. aureus. This idea provides the possibility for the application of hydrogels in the process of biological wound healing.

Vertical transmission of the gut microbiota influences glucose metabolism in offspring of mice with hyperglycaemia in pregnancy.

BACKGROUND: Hyperglycaemia in pregnancy (HIP) is a common metabolic disorder that not only poses risks to maternal health but also associates with an increased risk of diabetes among offspring. Vertical transmission of microbiota may influence the offspring microbiome and subsequent glucose metabolism. However, the mechanism by which maternal gut microbiota may influence glucose metabolism of the offspring remains unclear and whether intervening microbiota vertical transmission could be used as a strategy to prevent diabetes in the offspring of mothers with HIP has not been investigated. So we blocked vertical transmission to investigate its effect on glucose metabolism in the offspring. RESULTS: We established a murine HIP model with a high-fat diet (HFD) and investigated the importance of vertical transmission of gut microbiota on the glucose metabolism of offspring via birth and nursing by blocking these events through caesarean section (C-section) and cross-fostering. After weaning, all offspring were fed a normal diet. Based on multi-omics analysis, biochemical and transcriptional assays, we found that the glucometabolic deficits in the mothers were subsequently 'transmitted' to the offspring. Meanwhile, the partial change in mothers' gut microbial community induced by HIP could be transmitted to offspring, supported by the closed clustering of the microbial structure and composition between the offspring and their mothers. Further study showed that the microbiota vertical transmission was blocked by C-section and cross-fostering, which resulted in improved insulin sensitivity and islet function of the offspring of the mothers with HIP. These effects were correlated with changes in the relative abundances of specific bacteria and their metabolites, such as increased relative abundances of Bifidobacterium and short-chain fatty acids. In particular, gut microbial communities of offspring were closely related to those of their foster mothers but not their biological mothers, and the effect of cross-fostering on the offspring's gut microbiota was more profound than that of C-section. CONCLUSION: Our study demonstrates that the gut microbiota transmitted via birth and nursing are important contributors to the glucose metabolism phenotype in offspring. Video Abstract.

Intermittent hypoxia is involved in gut microbial dysbiosis in type 2 diabetes mellitus and obstructive sleep apnea-hypopnea syndrome.

BACKGROUND: Obstructive sleep apnea (OSA)-hypopnea syndrome (OSAHS) has been recognized as a comorbidity of type 2 diabetes mellitus (T2DM); more than half of T2DM patients suffer from OSAHS. Intermittent hypoxia (IH) plays an important role in metabolic diseases, such as obesity and OSAHS, through various mechanisms, including altering the gut microecological composition and function. Therefore, it is important to study the role of gut microbiota in T2DM patients with OSAHS, which has a high incidence and is prone to several complications. AIM: To assess whether IH is involved in altering the fecal microbiome in T2DM patients with OSAHS. METHODS: Seventy-eight participants were enrolled from Henan Province People's Hospital and divided into healthy control (HC, n = 26), T2DM (n = 25), and T2DM + OSA (n = 27) groups based on their conditions. The fecal bacterial DNA of the research participants was extracted and subjected to 16S ribosomal RNA sequencing. The clinical indices, such as insulin resistance index, homocysteine (HCY) concentration, and the concentrations of inflammatory factors in the peripheral blood, were assessed and recorded. RESULTS: Group T2DM + OSA had the highest apnea-hypopnea index (AHI) (2.3 vs 3.7 vs 13.7), oxygen desaturation index (0.65 vs 2.2 vs 9.1), HCY concentration (9.6 µmol/L vs 10.3 µmol/L vs 13.81 µmol/L) and C-reactive protein (CRP) concentrations (0.3 mg/L vs 1.43 mg/L vs 2.11 mg/L), and lowest mean oxygen saturation (97.05% vs 96.6% vs 94.7%) among the three groups. Twelve and fifteen key differences in amplicon sequence variants were identified when comparing group T2DM + OSA with groups T2DM and HC, respectively. We found progressively decreased levels of Faecalibacterium, Eubacterium, and Lachnospiraceae, and an increase in the level of Actinomyces, which strongly correlated with the HCY, CRP, fasting plasma glucose, and hemoglobin A1c concentrations, AHI, mean oxygen saturation, and insulin resistance index in group T2DM + OSA (P < 0.05). CONCLUSION: For T2DM patients with OSAHS, IH may be involved in selective alterations of the gut microbiota, which may affect the pathophysiological development of T2DM and DM-related complications.

Functionalizable and Chemically Recyclable Thermoplastics from Chemoselective Ring-Opening Polymerization of Bio-renewable Bifunctional α-Methylene-δ-valerolactone.

It is a highly attractive strategy to develop chemically recyclable polymers to establish a circular plastic economy. Despite the recent advancements, chemically recyclable polymers still face challenges including high energy cost for polymer preparation or recycling, poor monomer recovery selectivity and efficiency as well as undesired material performance. In this contribution, we present the chemoselective controlled ring-opening polymerization of bio-renewable bifunctional α-methylene-δ-valerolactone (MVL) to produce exclusive functionalizable polyester using strong base/urea binary catalysts. The obtained polyester with high molar mass exhibits good tensile strength comparable to that of some commodity plastics. Remarkably, the obtained polyester can be depolymerized to recover pristine monomer with a 96 % yield by thermolysis, thus successfully establishing a closed-loop life cycle.

2-Hydroxy-4-Methylselenobutanoic Acid Promotes Follicle Development by Antioxidant Pathway.

Selenium (Se) is assumed to promote the follicle development by attenuating oxidative stress. The current study was developed to evaluate the effects of dietary 2-hydroxy-4-methylselenobutanoic acid (HMSeBA) supplementation on the follicle development in vivo and on the function of ovarian granulosa cells (GCs) in vitro. Thirty-six gilts were randomly assigned to fed control diet (CON), Na2SeO3 diet (0.3 mg Se/kg) or HMSeBA diet (0.3 mg Se/kg). The results showed that HMSeBA and Na2SeO3 supplementation both increased the total selenium content in liver and serum compared with control, while HMSeBA increased the total selenium content in liver compared with Na2SeO3 group. HMSeBA tended to increase the total selenium content in ovary compared with control. HMSeBA and Na2SeO3 supplementation both increased the weight of uteri in gilts at the third estrus. Moreover, HMSeBA supplementation down-regulated the gene expression of growth differentiation factor-9 (GDF-9) and bone morpho-genetic protein-15 (BMP-15) in cumulus-oocyte complexes (COCs). HMSeBA supplementation decreased malondialdehyde (MDA) content in serum, liver and ovary, increased activity of T-AOC in liver, TXNRD in ovary and GPX in serum, liver and ovary, while up-regulated the liver GPX2, SOD1 and TXNRD1, ovarian GPX1 gene expression. In vitro, HMSeBA treatment promoted GCs' proliferation and secretion of estradiol (E2). HMSeBA treatment increased the activity of T-AOC, T-SOD, GPX, TXNRD and decreased MDA content in GCs in vitro. Meanwhile, HMSeBA treatment up-regulated SOD2 and GPX1 gene expression in GCs in vitro. In conclusion, HMSeBA supplementation is more conducive to promoting follicle development by antioxidant pathway.

Indigenous functional microbial degradation of the chiral fungicide mandipropamid in repeatedly treated soils: Preferential changes in the R-enantiomer.

This study investigated the indigenous functional microbial communities associated with the degradation of chiral fungicide mandipropamid enantiomers in soils repeatedly treated with a single enantiomer. The R-enantiomer degraded faster than the S-enantiomer, with degradation half-lives ranging from 10.2 d to 79.2 d for the R-enantiomer and 10.4 d to 130.5 d for the S-enantiomer. Six bacterial genera, (Burkholderia, Paraburkholderia, Hyphomicrobium, Methylobacterium, Caballeronia, and Ralstonia) with R-enantiomer substrate preference and three bacterial genera (Haliangium, Sorangium, and Sandaracinus) with S-enantiomer substate preference were responsible for the preferential degradation of the R-enantiomer and S-enantiomer, respectively. KEGG analysis indicated that Burkholderia, Paraburkholderia, Hyphomicrobium, and Methylobacterium were the dominant contributors to soil microbial metabolic functions. Notably, six microbial metabolic pathways and twelve functional enzyme genes were associated with the preferential degradation of the R-enantiomer, whose relative abundances in the R-enantiomer treatment were higher than those in the S-enantiomer treatment. A constructed biodegradation gene (BDG) protein database analysis further confirmed that Burkholderia, Paraburkholderia, Hyphomicrobium, Methylobacterium, and Ralstonia were the potential hosts of five dominant BDGs, bphA1, benA, bph, p450, and ppah. We concluded that bacterial genera Burkholderia, Paraburkholderia, Hyphomicrobium, and Methylobacterium may play pivotal roles in the preferential degradation of mandipropamid R-enantiomer in repeatedly treated soils.

Cardiovascular Benefits of Empagliflozin Are Associated With Gut Microbiota and Plasma Metabolites in Type 2 Diabetes.

CONTEXT: Cardiovascular benefits of empagliflozin in patients with type 2 diabetes mellitus (T2DM) have been reported; however, the underlying mechanism remains unknown. OBJECTIVE: We hypothesized that the cardiovascular benefits of empagliflozin are associated with altered gut microbiota and plasma metabolites, and that empagliflozin may be used as an initial treatment for patients with T2DM at risk of cardiovascular diseases (CVDs). METHODS: This randomized, open-label, 3-month, 2-arm clinical trial included 76 treatment-naïve patients with T2DM and risk factors for CVD who were treated with either empagliflozin (10 mg/d, n = 40) or metformin (1700 mg/d, n = 36). We investigated changes in clinical parameters related to glucose metabolism and CVD risk factors, gut microbiota using 16S rRNA gene sequencing, and plasma metabolites using LC-MS. RESULTS: We found significant and similar reduction in HbA1c levels and alleviation of glucose metabolism in both groups. However, only empagliflozin improved CVD risk factors. Empagliflozin significantly reshaped the gut microbiota after 1 month of treatment; this alteration was maintained until the end of the trial. Empagliflozin increased the levels of plasma metabolites such as sphingomyelin, but reduced glycochenodeoxycholate, cis-aconitate, and uric acid levels. Concurrently, empagliflozin elevated levels of short-chain fatty acid-producing bacteria such as species from Roseburia, Eubacterium, and Faecalibacterium, and reduced those of several harmful bacteria including Escherichia-Shigella, Bilophila, and Hungatella. CONCLUSION: Empagliflozin may be a superior initial therapy for patients with T2DM at risk of CVDs; its cardiovascular benefits may be associated with shifts in gut microbiota and plasma metabolites.

Berbamine reduces body weight via suppression of small GTPase Rab8a activity and activation of paraventricular hypothalamic neurons in obese mice.

Small GTPase Rab8a is involved in fat-specific protein 27 (Fsp27) mediated lipid droplet accumulation in adipocytes. By screening inhibitors of Rab8a GTPase from a natural compound library, berbamine (BBM), a marketing drug for treatment of leukopenia in China, was identified to inhibit the activity of Rab8a GTPase and block the differentiation of 3T3-L1 adipocytes. Animal study showed that BBM could reduce body weight, improved glucose and lipid metabolic homeostasis in high-fat diet-induced obesity (DIO) C57BL/6 mice and db/db mice. Additional, BBM increased energy expenditure and inhibited food intake in mice but not in lean mice. Moreover, intracerebroventricular injection (i.c.v.) of BBM inhibited feeding behavior and increased c-Fos expression in paraventricular nucleus of the hypothalamus (PVH) of mice. Our data suggest that BBM may improve obesity through the inhibition of Rab8a GTPase activity and the activation of anorexigenic energy-sensing neuron in PVH.

Effect of yeast culture supplementation in sows during late gestation and lactation on growth performance, antioxidant properties, and intestinal microorganisms of offspring weaned piglets.

Introduction: The effects of maternal addition of yeast cultures on offspring gut development and intestinal microorganisms are not yet known, so the aim of this study was to investigate the effects of maternal addition of yeast cultures to the diet of sows during late gestation and lactation on growth performance, antioxidant properties and intestinal microorganisms of offspring weaned piglets. Methods: 40 Landrace × Yorkshire sows (3-7 of parity) with similar backfat were randomly divided into two treatment groups: control diet (CON) and control diet +2.0 g/kg yeast culture (XPC), and the trial started on day 90 of gestation and ended on day 21 of lactation. Results: The results showed that maternal addition of yeast culture significantly increased weaned piglet weight and mean daily gain (p < 0.05), with a tendency to increase litter weight gain (p = 0.083) and liver weight (p = 0.076) compared to the control group. The content of thymus malondialdehyde (MDA) was significantly higher (p < 0.05) and the content of colon total antioxidant capacity (T-AOC) was significantly lower (p < 0.05) in the offspring weaned piglets of the XPC group compared to the control group. The expression of thymus SOD1 and SOD2, spleen SOD1, jejunum SOD2, and colon GPX1, SOD1, and SOD2 were significantly downregulated in the XPC group of offspring weaned piglets compared with the control group (p < 0.05). The intestinal morphology and the content of short-chain fatty acids in colonic chyme did not differ between the two groups (p > 0.05). Compared with the control group, the XPC group significantly increased the relative abundance of colonic chyme Bacteroidetes (p < 0.05), tended to decrease the relative abundance of Lactobacillus (p = 0.078), and tended to increase the relative abundance of Alloprevotella (p = 0.055). The XPC group significantly upregulated Blautia and Fournierella (p < 0.05) and significantly downregulated Candidatus_Competibacter, Nitrospira, Dechloromonas, Haliangium, and Oscillospira (p < 0.05). Discussion: In conclusion, maternal addition of yeast cultures improved the growth performance of offspring weaned piglets and changed the intestinal microbial community, but did not improve their antioxidant performance.

Aberrant expression of inhibitory receptors on B cells in patients with Graves' disease.

The pathophysiological mechanism underlying Graves' disease (GD) remains incompletely understood. Inhibitory receptors on B cells are critical for humoral immunity, which plays a key role in GD pathogenesis. This study aimed to investigate B cell subsets distribution and inhibitory receptor expression on these subsets in GD patients. Peripheral blood was drawn from 41 healthy controls and 46 GD patients (21 patients with moderate GD, 25 patients with severe GD). B cell subset distribution and CD22, CD32b and CD72 expression on B cells were analyzed by flow cytometry. Serum cytokines were examined by enzyme-linked immunosorbent assay (ELISA). Compared with healthy controls, the naïve B cell percentage was increased, while the preswitched memory and conventional memory B cell percentages were decreased. The inhibitory receptors expression, especially CD32b, on B cell subsets was significantly decreased in patients with GD. In addition, the inhibitory receptors expression on B cell subsets from severe GD patients exhibited a decreasing trend compared with those from moderate GD patients. These results suggest that abnormal B cell subset distribution occurs in GD. Impaired inhibitory receptors, in particular CD32b, play a crucial role in GD pathogenesis and might be a therapeutic target to rebuild self-immune tolerance in GD.

A ratiometric fluorescence sensor based on carbon quantum dots realized the quantitative and visual detection of Hg2.

In this paper, based on the fluorescence of carbon quantum dots (CQDs) quenched by mercury ions (Hg2+ ) and the nonresponse of Hg2+ to rhodamine B fluorescence, a dual emission ratio fluorescence sensor was constructed to realize the quantitative detection of Hg2+ . Under excitation at 365 nm, the fluorescence spectrum showed double emission peaks at 437 nm and 590 nm, corresponding to the fluorescence emissions of CQDs and rhodamine B, respectively. This method quantitatively detected Hg2+ based on the linear relationship between the ratio of the intensities of the two emission peaks F437 /F590 and the concentration of Hg2+ . The detection range was 10-70 nM, and the limit of detection (S/N = 3) was 3.3 nM. In addition, this method could also realize the qualitative and semiquantitative detection of Hg2+ according to the fluorescence colour change of the probe under ultraviolet light. After various evaluations, the method could be successfully applied to the quantitative and visual detection of Hg2+ in tap water, and demonstrated excellent selectivity, anti-interference performance, and repeatability of the method.