A multi-kingdom collection of 33,804 reference genomes for the human vaginal microbiome.

The human vagina harbours diverse microorganisms-bacteria, viruses and fungi-with profound implications for women's health. Genome-level analysis of the vaginal microbiome across multiple kingdoms remains limited. Here we utilize metagenomic sequencing data and fungal cultivation to establish the Vaginal Microbial Genome Collection (VMGC), comprising 33,804 microbial genomes spanning 786 prokaryotic species, 11 fungal species and 4,263 viral operational taxonomic units. Notably, over 25% of prokaryotic species and 85% of viral operational taxonomic units remain uncultured. This collection significantly enriches genomic diversity, especially for prevalent vaginal pathogens such as BVAB1 (an uncultured bacterial vaginosis-associated bacterium) and Amygdalobacter spp. (BVAB2 and related species). Leveraging VMGC, we characterize functional traits of prokaryotes, notably Saccharofermentanales (an underexplored yet prevalent order), along with prokaryotic and eukaryotic viruses, offering insights into their niche adaptation and potential roles in the vagina. VMGC serves as a valuable resource for studying vaginal microbiota and its impact on vaginal health.

Metagenomic-based characterization of the gut virome in patients with polycystic ovary syndrome.

Background: Polycystic ovary syndrome (PCOS) is a complex disease that afflicts women of reproductive age, and its pathological mechanism has not been well explained. The gut microbiota is believed to be closely related to the development of PCOS. Although an important component of the gut microbiome, the role of the gut virome in the development of PCOS is still unclear. Methods: In this study, we profiled and compared the gut viral community of 50 patients with PCOS and 43 healthy women based on the analysis of their fecal whole-metagenome dataset. Results: The gut virome of PCOS patients exhibited a significant decrease in within-sample viral diversity and a remarkable alteration of the overall virome composition compared with that of healthy controls. At the family level, Siphoviridae was significantly depleted in the gut virome of patients, while Quimbyviridae was enriched. We identified 1,089 viral operational taxonomic units (vOTUs) that differed in relative abundance between the two groups, of which 455 vOTUs were enriched in PCOS patients (including numerous Bacteroidaceae phages) and 634 were enriched in controls (including numerous viruses predicted to infect Oscillospiraceae, Prevotellaceae, and Ruminococcaceae). Functional comparison of the PCOS-enriched and control-enriched vOTUs uncovered the viral functional signatures associated with PCOS. Furthermore, we demonstrated gut viral signatures for disease discrimination and achieved an area under the receiver operator characteristic curve (AUC) of 0.938, demonstrating the potential of the gut virome in the prediction of PCOS. Conclusion: Our findings reveal specific alterations in viral diversity and taxonomic and functional compositions of the gut virome of PCOS patients. Further studies on the etiology of PCOS and the gut viral community will offer new prospects for treating and preventing PCOS and its related diseases.

Retracted: Effect of Cinnamaldehyde on Glucose Metabolism and Vessel Function.

This paper was retracted on the authors' request due to duplicate publication. This experiment was entrusted to a third party called Nanjing Changcong Biology Company, and we found that some of the data reported in the Results figures were duplicated in another published paper. The pdf file of the above-mentioned paper is available from the Editorial Office on request.

Isoquercitrin activates the AMP-activated protein kinase (AMPK) signal pathway in rat H4IIE cells.

BACKGROUND: Isoquercitrin, a flavonoid compound that is widely distributed in medicinal and dietary plants, possesses many biological activities, including inhibition of adipocyte differentiation. In this study, we investigated the effect of isoquercitrin on lipid accumulation and its molecular mechanisms in rat hepatoma H4IIE cells. METHODS: To investigate the effect of isoquercitrin on lipid accumulation, H4IIE cells were induced by FFA and the total lipid levels were detected by Oil Red O staining. Furthermore, The protein levels of AMPK and acetyl-CoA carboxylase (ACC), the gene expressions of transcriptional factor, lipogenic genes, and adiponectin receptor 1 (AdipoR1) were analyzed by Western blotting and quantitative real-time PCR. To further confirm the pathway of isoquercitrin-mediated hepatic lipid metabolism, H4IIE cells were treated with an AMPK inhibitor and AdipoR1 siRNA. RESULTS: Isoquercitrin significantly enhances AMPK phosphorylation, downregulates sterol regulatory element binding protein transcription factor 1 (SREBP-1) and fatty acid synthase (FAS) gene expressions. Pretreatment with AMPK inhibitor, significantly decreased the AMPK phosphorylation and increased FAS expression stimulated by isoquercitrin. Isoquercitrin might also upregulate the expression of AdipoR1 dose-dependently via AMPK in the presence of an AMPK inhibitor and AdipoR1 siRNA. CONCLUSIONS: Isoquercitrin appears to regulate AMPK activation, thereby enhancing AdipoR1 expression, suppressing SREBP-1 and FAS expressions, and resulting in the regulation of lipid accumulation. These results suggest that isoquercitrin is a novel dietary compound that can be potentially be used to prevent lipid metabolic disorder and nonalcoholic fatty liver disease.

Guava leaf extracts promote glucose metabolism in SHRSP.Z-Leprfa/Izm rats by improving insulin resistance in skeletal muscle.

BACKGROUND: Metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) have been associated with insulin-resistance; however, the effective therapies in improving insulin sensitivity are limited. This study is aimed at investigating the effect of Guava Leaf (GL) extracts on glucose tolerance and insulin resistance in SHRSP.Z-Leprfa/Izm rats (SHRSP/ZF), a model of spontaneously metabolic syndrome. METHODS: Male rats at 7 weeks of age were administered with vehicle water or treated by gavage with 2 g/kg GL extracts daily for six weeks, and their body weights, water and food consumption, glucose tolerance, and insulin resistance were measured. RESULTS: Compared with the controls, treatment with GL extracts did not modulate the amounts of water and food consumption, but significantly reduced the body weights at six weeks post treatment. Treatment with GL extracts did not alter the levels of fasting plasma glucose and insulin, but significantly reduced the levels of plasma glucose at 60 and 120 min post glucose challenge, also reduced the values of AUC and quantitative insulin sensitivity check index (QUICKI) at 42 days post treatment. Furthermore, treatment with GL extracts promoted IRS-1, AKT, PI3Kp85 expression, then IRS-1, AMKP, and AKT308, but not AKT473, phosphorylation, accompanied by increasing the ratios of membrane to total Glut 4 expression and adiponectin receptor 1 transcription in the skeletal muscles. CONCLUSIONS: These data indicated that GL extracts improved glucose metabolism and insulin sensitivity in the skeletal muscles of rats by modulating the insulin-related signaling.

The antioxidant effect of carnosol in bovine aortic endothelial cells is mainly mediated via estrogen receptor α pathway.

Antioxidant action is critical for maintaining the normal cardiovascular function and vascular endothelial cell is an important target of estrogen action through estrogen receptor (ER) pathway. This study is carried out to explore the antioxidant effect of carnosol in bovine aortic endothelial cells (BAECs) via ER pathway. The ER subtype specific estrogenic effect of carnosol was further demonstrated by luciferase reporter gene assay in human embryonic kidney (HEK) 293 cells. Carnosol was extracted from Chinese medicine Rosmarinus officinalis. ER positive BAECs were employed in cell proliferation assay and cell apoptosis tests. Oxidative stress by intracellular reactive oxygen species (ROS) were measured via 2'7'-dichlorofluorescein (DCF) production. ERα and ERß specific antagonists 1,3-bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]-1H-pyrazole (MPP) and 4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-3-yl]phenol (PHTPP) were employed as tools in the experiment. ER negative HEK 293 cells were employed in luciferase reporter gene assay. The results indicate that carnosol can effectively attenuate H(2)O(2) induced slowing down of cell growth and increasing of cell apoptosis. At the meantime, carnosol pretreating can also effectively reduce the H(2)O(2) induced intracellular ROS elevation in BAECs. ERα and ERß antagonist, especially ERα antagonist, can effectively decrease the above antioxidant effects of carnosol. The reporter gene analysis further demonstrates that the action of carnosol on inducing ERE dependent luciferase expression is realized via ER pathway. The conclusion is that carnosol can exert antioxidant effects towards oxidative stress induced by H(2)O(2) in BAECs. And such effects are realized via ER, especially ERα pathway. The results contribute to explain the mechanism of cardiovascular protective function of carnosol in postmenopausal women.

Association of copy number variation in the AHI1 gene with risk of obesity in the Chinese population.

OBJECTIVE: The prevalence of obesity has increased dramatically over the past decade. Gene copy number variants (CNVs) have been recognized as a hereditable source of susceptibility in human complex diseases including obesity. Recent studies have shown that Abelson helper integration site 1 (Ahi1) gene has a significant contribution in the homeostasis regulation in mouse models of obesity. A study was therefore carried out to investigate whether CNVs in AHI1 gene contribute to human obesity. SUBJECTS AND METHODS: We analyzed samples from 70 Chinese overweight adults and 74 healthy controls for DNA copy number change using the Affymetrix single-nucleotide polymorphism (SNP) 6.0 array. Validation of CNVs of AHI1 was achieved by real-time PCR using the ΔΔC(t) method. RESULTS: Copy number gain analysis revealed significant gains (P=0.0017) of AHI1 gene copy number in 17 of 70 (24.3%) samples but only four of 74 (5.4%) controls overall. Then we studied the frequency distribution of CNVs in AHI1 gene according to body mass index (BMI) grade. Five out of 28 (18.5%) at-risk obese, six out of 26 (26.9%) moderate obese, and six out of 17 (29.4%) severe obese subjects studied showed increased AHI1 gene copy number. CONCLUSIONS: The result suggested that there was a significant linear trend for increasing AHI1 gene copy number frequencies with increasing BMI.

Hypothalamic Ahi1 mediates feeding behavior through interaction with 5-HT2C receptor.

It is indicated that there are important molecules interacting with brain nervous systems to regulate feeding and energy balance by influencing the signaling pathways of these systems, but relatively few of the critical players have been identified. In the present study, we provide the evidence for the role of Abelson helper integration site 1 (Ahi1) protein as a mediator of feeding behavior through interaction with serotonin receptor 2C (5-HT(2C)R), known for its critical role in feeding and appetite control. First, we demonstrated the co-localization and interaction between hypothalamic Ahi1 and 5-HT(2C)R. Ahi1 promoted the degradation of 5-HT(2C)R through the lysosomal pathway. Then, we investigated the effects of fasting on the expression of hypothalamic Ahi1 and 5-HT(2C)R. Fasting resulted in an increased Ahi1 expression and a concomitant decreased expression of 5-HT(2C)R. Knockdown of hypothalamic Ahi1 led to a concomitant increased expression of 5-HT(2C)R and a decrease of food intake and body weight. Last, we found that Ahi1 could regulate the expression of neuropeptide Y and proopiomelanocortin. Taken together, our results indicate that Ahi1 mediates feeding behavior by interacting with 5-HT(2C)R to modulate the serotonin signaling pathway.

Antidiabetic effects of Tangnaikang on obese Zucker rats and the mechanism.

OBJECTIVE: To observe the effects of Tangnaikang (TNK), a compound traditional Chinese herbal medicine, on glucose metabolism and insulin resistance in obese Zucker rats. METHODS: Twelve male obese Zucker rats, 6 weeks old, were randomly divided into control group and TNK group (3.24 g/kg) after being fed for 2 weeks. All rats received high-fat diet and 4-week treatment. Body weight and blood glucose were tested every week. Oral glucose tolerance test (OGTT) was performed and fasting insulin level was tested on days 0, 14 and 28. Triglyceride, cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and free fatty acids (FFA) were tested on day 28. Glucose infusion rate (GIR) was tested by hyperinsulinemic-euglycemic clamp from day 29. The protein expressions of protein kinase B (Akt), phospho-Akt (p-Akt) (Thr308) and glucose transporter protein 4 (GLUT4) in skeletal muscle and GLUT4 in adipose tissue were measured after hyperinsulinemic-euglycemic clamp test. RESULTS: Compared with the control group, the fed blood glucose level and glucose level of OGTT at 120 min had a significant decline in TNK group on day 28, and TNK caused no alteration of the fasting serum insulin, and the GIR increased significantly in hyperinsulinemic-euglycemic clamp study. Furthermore, TNK increased Akt and p-Akt (Thr308) protein expressions in skeletal muscle and decreased the protein expression of GLUT4 in white adipose tissue. Body weight, and triglyceride, cholesterol, LDL-C and FFA contents were slightly decreased in the TNK group, but there were no statistically significant effects. CONCLUSION: TNK increases the protein expressions of Akt and p-Akt (Thr308) of the signal transduction pathway to influence the translocation of GLUT4 in skeletal muscle and improves glucose metabolism by reducing insulin resistance.