Gut microbiota and type 2 diabetes mellitus: a focus on the gut-brain axis.

Type 2 diabetes mellitus (T2DM) has become one of the most serious public healthcare challenges, contributing to increased mortality and disability. In the past decades, significant progress has been made in understanding the pathogenesis of T2DM. Mounting evidence suggested that gut microbiota (GM) plays a significant role in the development of T2DM. Communication between the GM and the brain is a complex bidirectional connection, known as the "gut-brain axis," via the nervous, neuroendocrine, and immune systems. Gut-brain axis has an essential impact on various physiological processes, including glucose metabolism, food intake, gut motility, etc. In this review, we provide an outline of the gut-brain axis. We also highlight how the dysbiosis of the gut-brain axis affects glucose homeostasis and even results in T2DM.

Update on N6-methyladenosine methylation in obesity-related diseases.

Obesity is a chronic metabolic disease that is closely related to type 2 diabetes mellitus, cardiovascular diseases, nonalcoholic fatty liver disease, obstructive sleep apnea, and osteoarthritis. The prevalence of obesity is increasing rapidly every year and is recognized as a global public health problem. In recent years, the role of epigenetics in the development of obesity and related diseases has been recognized and is currently a research hotspot. N6-methyladenosine (m6A) methylation is the most abundant epigenetic modification in the eukaryotic RNA, including mRNA and noncoding RNA. Several studies have shown that the m6A modifications in the target mRNA and the corresponding m6A regulators play a significant role in lipid metabolism and are strongly associated with the pathogenesis of obesity-related diseases. In this review, the latest research findings regarding the role of m6A methylation in obesity and related metabolic diseases are summarized. The authors' aim is to highlight evidence that suggests the clinical utility of m6A modifications and the m6A regulators as novel early prediction biomarkers and precision therapeutics for obesity and obesity-related diseases.

Association of metabolically unhealthy non-obese and metabolically healthy obese individuals with arterial stiffness and 10-year cardiovascular disease risk: a cross-sectional study in Chinese adults.

BACKGROUND: The relationship between metabolically healthy obese individuals (MHO) and cardiovascular disease (CVD) risk is disputed. This study investigated the association of metabolically unhealthy non-obese(MUNO) individuals and MHO with arterial stiffness and 10-year CVD risk. METHODS: A total of 13,435 participants were enrolled and further divided into the metabolically healthy non-obese (MHNO) phenotype (n = 4927), MUNO phenotype (n = 1971), MHO phenotype (n = 2537) and metabolically unhealthy obese (MUO) phenotype (n = 4000) according to body mass index (BMI) and metabolic status. We used brachial ankle pulse wave velocity (baPWV) to measure arterial stiffness and the Framingham risk score (FRS) to evaluate the 10-year CVD risk. RESULTS: The MUO and MUNO phenotypes had higher mean baPWV values than the MHO and MHNO phenotypes, regardless of age (1446.19 ± 233.65 vs. 1423.29 ± 240.72 vs. 1283.57 ± 213.77 vs. 1234.08 ± 215.99 cm/s, P < 0.001). Logistic regression analysis indicated that the MUNO and MUO phenotypes were independently correlated with elevated baPWV and 10-year CVD risk, while the MHO phenotype was independently associated with only the 10-year CVD risk. In metabolically healthy subjects, BMI showed a dose-dependent increase in the risk of elevated baPWV, with an adjusted OR of 1.007 (95% CI 1.004-1.010, P < 0.001). However, in metabolically unhealthy participants, the estimate for the relationship between elevated baPWV and BMI was nonsignificant. CONCLUSIONS: The MUNO phenotype exhibits increased arterial stiffness and 10-year CVD risk. However, BMI is positively and dose-dependently correlated with arterial stiffness only in metabolically healthy subjects. We speculate that metabolic status may be a strong confounder in the obesity-elevated baPWV association.

Identification of Basement Membrane Genes and Related Molecular Subtypes in Nonalcoholic Fatty Liver Disease.

Basement membranes (BMs) are widely distributed and highly specialized extracellular matrix (ECM). The goal of this study was to explore novel genes associated with nonalcoholic fatty liver disease (NAFLD) from the perspective of BMs. Sequencing results of 304 liver biopsy samples about NAFLD were systematically obtained from the Gene Expression Omnibus (GEO) database. Biological changes during NAFLD progression and hub BM-associated genes were investigated by differential gene analysis and weighted gene co-expression network analysis (WGCNA), respectively. The nonalcoholic steatohepatitis (NASH) subgroups were identified based on hub BM-associated genes expression, as well as the differences in Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways and immune microenvironment between different subgroups were compared. Extracellular matrix (ECM) seems to play an important role in the development of NAFLD. Three representative BM-associated genes (ADAMTS2, COL5A1, and LAMC3) were finally identified. Subgroup analysis results suggested that there were significant changes in KEGG signaling pathways related to metabolism, extracellular matrix, cell proliferation, differentiation, and death. There were also changes in macrophage polarization, neutrophils, and dendritic cells abundance, and so on. In conclusion, the present study identified novel potential BM-associated biomarkers and further explored the heterogeneity of NASH that might provide new insights into the diagnosis, assessment, management, and personalized treatment of NAFLD.

Exploring the role of gut microbiota in obesity and PCOS: Current updates and future prospects.

Polycystic ovary syndrome (PCOS) is a common endocrine gynecological disorder, and the specific pathogenesis of PCOS has not been elucidated. Obesity is a current major public health problem, which is also vital to PCOS. It can exacerbate PCOS symptoms via insulin resistance and hyperandrogenemia. The treatment of PCOS patients depends on the prevailing symptoms. Lifestyle interventions and weight loss remain first-line treatments for women with PCOS. The gut microbiota, which is a current research hot spot, has a substantial influence on PCOS and is closely related to obesity. The present study aimed to elucidate the function of the gut microbiota in obesity and PCOS to provide new ideas for the treatment of PCOS.

Single-cell transcriptomics dissects epithelial heterogeneity in HPV+ cervical adenocarcinoma.

The intra- and intertumoral heterogeneity of epithelial cells in human papillomavirus (HPV+ ) cervical adenocarcinoma (CEAD) remains largely unknown. To investigate this issue, we performed single-cell RNA sequencing on 19 229 epithelial cells sorted from three tumor samples of three patients with HPV+ CEAD. Six epithelial subclusters (Epi1-Epi6) were identified that showed distinct gene expression. Among these, Epi1 and Epi4 had apparent tumor hallmarks and metabolic activities. Epi1 was highly enriched in hallmarks of hypoxia, IL2/STAT5 signaling, retinol metabolism, glycolysis, and arachidonic acid metabolism, while Epi4 was highly enriched in hallmarks of G2M checkpoint, E2F targets, DNA repair, PI3K/AKT/MTOR signaling, glycolysis, fatty acid degradation, TCA cycle, and glutathione metabolism. We also investigated intertumoral epithelial heterogeneity and found that Patient 1 was highly enriched for KRAS signaling and angiogenesis, while Patient 2 was highly enriched for epithelial-mesenchymal transition and TGF-ß signaling, and Patient 3 was highly enriched for hypoxia, DNA repair, G2M checkpoint, and E2F targets. Using single-cell RNA sequencing, we revealed the intra- and intertumoral heterogeneity of epithelial cells in HPV+ CEAD, providing insights into the importance of personalized treatment for patients with HPV+ CEAD.

Association of serum Tsukushi level with metabolic syndrome and its components.

PURPOSE: Tsukushi (TSK), a novel hepatokine, has recently been pointed out to play an important role in energy homeostasis and glycolipid metabolism. However, there are no clinical studies on the association of TSK with metabolic syndrome (MetS), the typical constellation of metabolic disorders. This study was conducted to explore the relationship between TSK and MetS as well as each of its metabolic component clinically. METHODS: We analyzed in this cross-sectional study serum TSK levels by ELISA in 392 participants, including 90 non-MetS and 302 MetS, to compare TSK in two groups and in different numbers of metabolic components. The odds ratios (OR) of TSK quartile in MetS and each metabolic component were computed by multivariate logistic regression analysis. RESULTS: TSK was substantially higher in MetS than in non-MetS subjects (P < 0.001). TSK increased with the concomitant increase of the number of metabolic components (P for <0.001). Logistic regression analyses demonstrated that the OR of MetS was 2.74 for the highest versus the lowest quartile of TSK (P < 0.001) after adjusting for age, gender, smoking status, alcohol consumption and medication use. Additionally, TSK was associated with the OR of poor HDL-C and elevated fasting glucose (P < 0.05). CONCLUSION: Circulating TSK was higher in MetS patients and linked with MetS risk, suggesting that TSK may play a role in the genesis of MetS and be a potential therapeutic target for MetS. Future study should investigate the connection between TSK levels and MetS pathogenesis.

Weighted Gene Co-Expression Network Analysis of Immune Infiltration in Nonalcoholic Fatty Liver Disease.

BACKGROUND: Immune cell infiltration is an important component of nonalcoholic fatty liver disease (NAFLD) pathogenesis. This study aimed to explore novel genes associated with immune infiltration in the progression of NAFLD. METHODS: CIBERSORT was used to evaluate the abundance of immune infiltration in the human NAFLD via a high-throughput sequencing dataset. Further weighted gene co-expression network analysis (WGCNA) was performed to search for the susceptibility gene module and hub genes associated with differential immune cells. The expression of hub genes in different liver non-parenchymal cell clusters and NAFLD-associated hepatocellular carcinoma (HCC) was also explored. RESULTS: Four hub genes (ITGBL1, SPINT1, COL1A2, and THBS2) were ultimately identified, which may be associated with immune infiltration, fibrosis progression, and activity score. The receiver operating characteristic curve (ROC) analysis suggested that these genes had good predictive value for NASH and advanced fibrosis. A single-cell analysis showed that COL1A2 was highly expressed in hepatic stellate cells (HSCs), especially in the later stage, while SPINT1 was highly expressed in cholangiocytes (Cho). In addition, ITGBL1, COL1A2, and THBS2 might be associated with transforming from nonalcoholic steatohepatitis (NASH) to HCC. Our findings identified several novel genes that might be related to immune infiltration in NAFLD. CONCLUSION: These genes may serve as potential markers for the assessment of immune infiltration as well as therapeutic targets for NAFLD. More studies are needed to elucidate the biological mechanism of these genes in the occurrence and development of NAFLD.

[Application of 20% glucose solution in the treatment of diabetic patients with hypoglycemia].

OBJECTIVE: To explore the safety and efficacy of 20% glucose solution in the treatment of adult diabetic patients with hypoglycemia. METHODS: A non-randomized controlled paired design trial was conducted. The diabetes patients with hypoglycemia (blood glucose < 3.9 mmol/L) who were admitted to the department of endocrinology and metabolism of Affiliated Hospital of Jiangsu University from December 2020 to May 2021 were enrolled. When the patients developed hypoglycemia for the first time, 75 mL of 20% glucose solution was pumped intravenously at a constant speed within 15 minutes, which was named the 20% glucose solution group. When the patients had hypoglycemia again, 30 mL of 50% glucose solution was pumped intravenously at a constant speed within 3 minutes, which was named the 50% glucose solution group. If the blood glucose was still ≤ 3.9 mmol/L at 15 minutes of hypoglycemia treatment, or the patients were uncomfortable due to too fast drip speed, it should be terminated immediately. The hypoglycemia treatment should be handled according to the Chinese guidelines for the prevention and treatment of type 2 diabetes (2020 edition). The peripheral blood glucose level and the range of increase at 15 minutes of treatment, the success rate of one treatment, the peripheral blood glucose values at 60 minutes after successful hypoglycemia treatment, the incidence of phlebitis and exudation after hypoglycemia treatment, and the pain of local blood vessels in patients with hypoglycemia treatment were analyzed and compared between the two groups. RESULTS: A total of 65 patients completed the treatment of hypoglycemia with 20% glucose solution and the success rate of one treatment was 100%. The peripheral blood glucose value at 15 minutes of hypoglycemia treatment was (8.30±1.37) mmol/L, and the increased range was (4.86±1.30) mmol/L. The peripheral blood glucose value at 60 minutes after successful hypoglycemia treatment was (6.96±1.48) mmol/L, which indicated that 20% glucose solution could effectively increase blood glucose. Among 65 patients, 32 patients had hypoglycemia again, who were treated with 50% glucose solution, and the success rate of one treatment was 100%. When patients who received 50% glucose solution for hypoglycemia formed a paired design with the first 20% glucose solution treatment, the results showed that there was no significant difference in the peripheral blood glucose value and the increased range in blood glucose at 15 minutes of hypoglycemia treatment between the 20% glucose solution and the 50% glucose solution groups [peripheral blood glucose (mmol/L): 8.20 (7.70, 9.70) vs. 8.30 (7.80, 8.80), increase in blood glucose (mmol/L): 4.96±1.39 vs. 4.70±1.32, both P > 0.05], indicating that the glucose changing at 15 minutes of hypoglycemia treatment with 20% glucose solution was similar to that with 50% glucose solution. The peripheral blood glucose value at 60 minutes after successful hypoglycemia treatment of 20% glucose solution group was significantly lower than that of 50% glucose solution group (mmol/L: 6.37±1.04 vs. 7.20±1.36, P < 0.01), which meant that the blood glucose tended to be more stable. There was no phlebitis and exudation after hypoglycemia treatment in both groups. The pain score of 20% glucose solution group was 0, however, 3 patients in 50% glucose solution group complained of local vascular pain, and the pain score was 1. CONCLUSIONS: 20% glucose solution can effectively treat hypoglycemia in diabetic patients, which has the same curative effect as 50% glucose solution and much safer. It can be used in patients with severe hypoglycemia.

Transcriptome analysis of peripheral blood mononuclear cells in patients with type 1 diabetes mellitus.

PURPOSE: Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterized by the destruction of pancreatic ß cells. The goal of this study was to explore potential biological biomarkers for T1DM. METHODS: Two microarray datasets (GSE55098 and GSE156035) about human peripheral blood mononuclear cells (PBMCs) were systematically extracted from the Gene Expression Omnibus (GEO) database. Common genes were identified from the perspective of differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) respectively, and hub genes were identified by least absolute shrinkage and selection operator (LASSO) analysis. We also observed the expression of these hub genes in some common autoimmune diseases and predicted transcription factors (TFs) that might be associated with these genes. RESULTS: Seven hub genes (DDIT4, ESCO2, SH3BP4, PRICKLE1, EPM2AIP1, KCNJ15 and GRM8) were finally identified. Receiver operating characteristic (ROC) analysis showed that the high expression of these genes could well predict the occurrence of T1DM. Gene set enrichment analysis (GSEA) suggested that most of these hub genes may be mainly involved in the changes of biological functions such as inflammation, infection, immunity, cancer, and apoptosis. Further, compared with the control group, the expression levels of these hub genes also changed in some other autoimmune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary biliary cholangitis (PBC), etc., indicating that they might be the common targets of these autoimmune diseases. CONCLUSIONS: The present study identified novel genes associated with T1DM from the PBMCs perspective that might provide new ideas for the early diagnosis, monitoring, evaluation, and prediction of T1DM.

Comparing dosimetric and cancer control outcomes after intensity-modulated radiation therapy and tomotherapy for advanced cervical cancer.

Concurrent chemoradiation therapy (CCRT) is the standard treatment for locally advanced cervical cancer. The present study aimed to compare the therapeutic responses, toxicities and dosimetric parameters between intensity-modulated radiation therapy (IMRT) and tomotherapy (TOMO) in patients with advanced cervical cancer. This retrospective study included 310 patients with stage IIB-IIIB cervical cancer who underwent CCRT, with 155 patients in each group. Intracavitary brachytherapy was performed after a course of external beam radiation therapy (EBRT), or in the last week of pelvic EBRT. The treatment planning aim at point A (defined as a reference location 2 cm above the vaginal fornix and 2 cm beside the mid axis of the uterus) was >85 Gy in an equivalent dose at 2 Gy. There was no statistical difference with regard to clinicopathological characteristics between the two groups (P>0.05). Improved dose conformity and dose homogeneity (P<0.05) were observed in TOMO planning. TOMO provided more efficacious critical organ sparing than IMRT when assessing the percentage of normal tissue receiving at least 20 Gy (V20) for the bladder, the percentage of normal tissue receiving at least 40 Gy (V40) for the femoral head, and the V40 and V20 for the rectum (P<0.05). TOMO demonstrated a greater ability to protect the ovary (P<0.05). The acute radiation toxicity of proctitis and leukopenia were significantly lower in the TOMO group (P<0.05). The chronic radiation toxicity of radiation enterocolitis and cystitis was lower in the TOMO group (P<0.05). Thus, TOMO provided better critical organ sparing than IMRT. The radiation toxicities were acceptable. Therefore, TOMO appears to be a good option for the treatment of stage IIB-IIIB cervical cancer.

The Role of Fibroblast Growth Factor 19 Subfamily in Different Populations Suffering From Osteoporosis.

Fibroblast growth factor (FGF) 19 subfamily, also known as endocrine fibroblast growth factors (FGFs), is a newly discovered metabolic regulator, including FGF19, FGF21 and FGF23. They play significant roles in maintaining systemic homeostasis, regulating the balance of bile acid and glucolipid metabolism in humans. Osteoporosis is a chronic disease, especially in the current status of aging population, osteoporosis is the most prominent chronic bone disease, leading to multiple complications and a significant economic burden that requires long-term or even lifelong management. Members of the FGF family have been shown to be associated with bone mineral density (BMD), fracture repair and cartilage regeneration. Studies of the FGF19 subfamily in different populations with osteoporosis have been increasing in recent years. This review summarizes the role of the FGF19 subfamily in bone metabolism, and provides new options for the treatment of bone diseases such as osteoporosis.

Regulatory network of metformin on adipogenesis determined by combining high-throughput sequencing and GEO database.

Adipose differentiation and excessive lipid accumulation are the important characteristics of obesity. Metformin, as a classic hypoglycaemic drug, has been proved to reduce body weight in type 2 diabetes, the specific mechanism has not been completely clear. A few studies have explored its effect on adipogenesis in vitro, but the existing experimental results are ambiguous. 3T3-L1 preadipocytes were used to explore the effects of metformin on the morphological and physiological changes of lipid droplets during adipogenesis. A high throughput sequencing was used to examine the effects of metformin on the transcriptome of adipogenesis. Considering the inevitable errors among independent experiments, we performed integrated bioinformatics analysis to identify important genes involved in adipogenesis and reveal potential molecular mechanisms. During the process of adipogenesis, metformin visibly relieved the morphological and functional changes. In addition, metformin reverses the expression pattern of genes related to adipogenesis at the transcriptome level. Combining with integrated bioinformatics analyses to further identify the potential targeted genes regulated by metformin during adipogenesis. The present study identified novel changes in the transcriptome of metformin in the process of adipogenesis that might shed light on the underlying mechanism by which metformin impedes the progression of obesity.

Angiopoietin-like protein 8 (betatrophin) inhibits hepatic gluconeogenesis through PI3K/Akt signaling pathway in diabetic mice.

BACKGROUND & AIMS: Angiopoietin-like protein 8 (ANGPTL8) is a 198 amino-acid long, novel secreted protein that is mainly expressed in the liver and brown adipose tissues. At present, evidence supporting the involvement of ANGPTL8 in the regulation of glucose metabolism is inconclusive, along with its function in the liver. Previous studies mainly focused on the effect of ANGPTL8 on glucose metabolism in non-diabetic mice, and few relevant studies in diabetic mice exist. Therefore, this study aimed to investigate the role of ANGPTL8 on glucose homeostasis and elucidate the underlying mechanisms in diabetic mice. METHODS: db/db diabetic and high-fat diet/streptozotocin-induced diabetic mice were injected with adenovirus expressing ANGPTL8 through the tail vein. Blood glucose levels were measured and glucose, insulin, and pyruvate tolerance tests were performed. To explore the molecular mechanism by which ANGPTL8 regulates hepatic glucose metabolism and manipulate mouse ANGPTL8 expression levels both in vivo and in vitro based on adenoviral transduction, gain- and loss-of-function strategies were adopted. RESULTS: Adenovirus-mediated overexpression of ANGPTL8 decreased fasting blood glucose levels and improved glucose tolerance and insulin sensitivity in db/db and high-fat diet/streptozotocin-induced diabetic mice. ANGPTL8 knockdown yielded the opposite effects. ANGPTL8 was upregulated in the cAMP/Dex-induced hepatocyte gluconeogenesis model. Moreover, ANGPTL8 overexpression in primary hepatocytes and diabetic mouse livers inhibited the expression of gluconeogenesis-related genes, including PEPCK and G6PC, by activating the AKT signaling pathway and, thereby, reducing glucose production. Therefore, the results demonstrated that ANGPTL8 improved glucose metabolism via inhibition of hepatic gluconeogenesis in diabetic mice. CONCLUSIONS: Current findings highlight a critical role of hepatic ANGPTL8 in glucose homeostasis, suggesting that increased ANGPTL8 expression could be an underlying factor for the inhibition of hepatic gluconeogenesis, which could be targeted for the prevention and treatment of type 2 diabetes.

Ectodysplasin A/Ectodysplasin A Receptor System and Their Roles in Multiple Diseases.

Ectodysplasin A (EDA) is a member of the tumor necrosis factor (TNF) family of ligands that was initially reported to induce the formation of various ectodermal derivatives during normal prenatal development. EDA exerts its biological activity as two splice variants, namely, EDA-A1 and EDA-A2. The former binds to the EDA receptor (EDAR), resulting in the recruitment of the intracellular EDAR-associated death domain (EDARADD) adapter protein and the activation of the NF-κB signaling pathway, while the latter binds to a different receptor, EDA2R, also known as X-linked ectodermal dysplasia receptor (XEDAR). Inactivation mutation of the EDA gene or the genes coding for its receptors can result in hypohidrosis ectodermal dysplasia (HED), a condition that is characterized by oligotrichosis, edentulosis or oligodontia, and oligohidrosis or anhidrosis. Recently, as a new liver factor, EDA is gradually known and endowed with some new functions. EDA levels were observed to be upregulated in several metabolic diseases, such as non-alcoholic fatty liver disease (NAFLD), obesity, and insulin resistance. In addition, EDA and its receptors have been implicated in tumor pathogenesis through the regulation of tumor cell proliferation, apoptosis, differentiation, and migration. Here, we first review the role of EDA and its two-receptor system in various signaling pathways and then discuss the physiological and pathological roles of EDA and its receptors.

Monocyte to High-Density Lipoprotein Cholesterol Ratio at the Nexus of Type 2 Diabetes Mellitus Patients With Metabolic-Associated Fatty Liver Disease.

Background: Recently, monocyte to high-density lipoprotein cholesterol ratio (MHR) as a novel inflammatory biomarker has drawn lots of attention. This study was conducted in patients with type 2 diabetes mellitus (T2DM) to investigate the correlation between MHR and metabolic-associated fatty liver disease (MAFLD). Methods: Totally, 1,051 patients with T2DM from the Affiliated Hospital of Jiangsu University were enrolled and classified as MAFLD (n = 745) group and non-MAFLD (n = 306) group according to the MAFLD diagnostic criteria. In contrast, patients were also separated into four groups based on MHR quartiles. Anthropometric and biochemical measurements were performed. The visceral fat area (VFA) and subcutaneous fat area (SFA) of participants were measured by dual bioelectrical impedance. Fatty liver was assessed by ultrasonography. Results: The MHR level of subjects in the MAFLD group was statistically greater than that in the non-MAFLD group (P < 0.05). Meanwhile, MHR was higher in the overweight or obese MAFLD group compared with that in the lean MAFLD group (P < 0.05). The area under the ROC Curve (AUC) assessed by MHR was larger than that of other inflammatory markers (P < 0.01). The cutoff value of MHR was 0.388, with a sensitivity of 61.74% and a specificity of 56.54%. For further study, binary logistic regression analyses of MAFLD as a dependent variable, the relationship between MHR and MAFLD was significant (P < 0.01). After adjusting for many factors, the relationship still existed. In the four groups based on MHR quartiles, groups with higher values of MHR had a significantly higher prevalence of MAFLD (P < 0.05). The percentage of patients with obese MAFLD increased as the MHR level increased (P < 0.01). Among different quartiles of MHR, it showed that with the increasing of MHR, the percentage of patients with MAFLD who had more than four metabolic dysfunction indicators increased, which was 46.39, 60.52, 66.79, and 79.91%, respectively, in each quartile. Conclusion: Monocyte to high-density lipoprotein cholesterol ratio is a simple and practicable inflammatory parameter that could be used for assessing MAFLD in T2DM. T2DM patients with higher MHR have more possibility to be diagnosed as MAFLD. Therefore, more attention should be given to the indicator in the examination of T2DM.

Circulating levels of fibroblast growth factor 21 in gestational diabetes mellitus: a meta-analysis.

In recent times, the role of fibroblast growth factor 21 (FGF21) in patients with gestational diabetes mellitus (GDM) has been increasingly investigated. However, to our knowledge, no systematic analysis has been conducted yet to evaluate the relationship between FGF21 levels and GDM. Confirmed studies related to circulating FGF21 levels and GDM were searched from the databases of PubMed, ISI Web of Science, MEDLINE and EMBASE. Data were reported as standard mean difference (SMD) and associated 95% confidence intervals (CIs). Analysis were performed with Review Manager 5.2 and Stata version 11.0. A total of 392 cases and 435 controls in nine articles were included in this meta-analysis. The circulating FGF21 levels in pregnant women with GDM was higher than that in controls (random effects MD [95% CI] = 0.46, [0.07-0.86], p = 0.02). The result of multivariate meta-regression showed that sample size and point of sample collection contributed to heterogeneity (p = 0.033 and p = 0.047, respectively). Additionally, the results showed that there was no publication bias in this meta-analysis (Z = 1.36, p = 0.175; t = 1.24, p = 0.256, respectively). To conclude, this meta-analysis provides evidence that circulating FGF21 levels are higher in GDM subjects than controls, and it is important to clarify the relationship between circulating FGF21 levels and pregnant women with GDM in accurate prediction of GDM.

The Effects of Platelet-Rich and Platelet-Poor Plasma on Biological Characteristics of BM-MSCs In Vitro.

Platelet-rich plasma (PRP) and its byproduct platelet-poor plasma (PPP) are rich sources of cytokines in tissue damage repair. Bone marrow-derived mesenchymal stem cells (BM-MSCs) have received more and more attention for their ability to treat multiple diseases. The purpose of our study was to investigate the biologic action of PPP and PRP on BM-MSCs. The adipogenic potential of BM-MSCs revealed no obvious change, but the osteogenic ability of BM-MSCs was enhanced after treated with PRP. CCK8 assays and cell colony formation assays showed that PRP promoted cell proliferation, while this effect of PPP was not obvious. No obvious difference was found in cell cycle and apoptosis of BM-MSCs between PRP and PPP treatment. Expression of ß-galactosidase, a biological marker of senescence, was decreased upon PRP treatment which indicated that PRP provided significant protection against cellular senescence. The migratory capacity of BM-MSCs was detected by scratch and transwell assays. The results indicated that PRP could affect the migration ability of BM-MSCs. From immunofluorescence detection and western blot, we demonstrated that the level of epithelial-mesenchymal transition-related proteins was changed and several pluripotency marker genes, including Sox2, Sall4, Oct4, and Nanog, were increased. Finally, the expression of the key signal pathway such as PI3K/AKT was examined. Our findings suggested that PRP promoted cell migration of BM-MSCs via stimulating the signaling pathway of PI3K/AKT.

Chemerin enhances the adhesion and migration of human endothelial progenitor cells and increases lipid accumulation in mice with atherosclerosis.

BACKGROUND: The role of adipokines in the development of atherosclerosis (AS) has received increasing attention in recent years. This study aimed to explore the effects of chemerin on the functions of human endothelial progenitor cells (EPCs) and to investigate its role in lipid accumulation in ApoE-knockout (ApoE-/-) mice. METHODS: EPCs were cultured and treated with chemerin together with the specific p38 mitogen-activated protein kinase (MAPK) inhibitor SB 203580 in a time- and dose-dependent manner. Changes in migration, adhesion, proliferation and the apoptosis rate of EPCs were detected. ApoE-/- mice with high-fat diet-induced AS were treated with chemerin with or without SB 203580. Weights were recorded, lipid indicators were detected, and tissues sections were stained. RESULTS: The data showed that chemerin enhanced the adhesion and migration abilities of EPCs, and reduced the apoptosis ratio and that this effect might be mediated through the p38 MAPK pathway. Additionally, chemerin increased the instability of plaques. Compared with the control group and the inhibitor group, ApoE-/- mice treated with chemerin protein had more serious arterial stenosis, higher lipid contents in plaques and decreased collagen. Lipid accumulation in the liver and kidney and inflammation in the hepatic portal area were enhanced by treatment with chemerin, and the size of adipocytes also increased after chemerin treatment. In conclusion, chemerin can enhance the adhesion and migration abilities of human EPCs and reduce the apoptosis ratio. In animals, chemerin can increase lipid accumulation in atherosclerotic plaques and exacerbate plaques instability. At the same time, chemerin can cause abnormal lipid accumulation in the livers and kidneys of model animals. After specifically blocking the p38 MAPK pathway, the effect of chemerin was reduced. CONCLUSIONS: In conclusion, this study showed that chemerin enhances the adhesion and migration abilities of EPCs and increases the instability of plaques and abnormal lipid accumulation in ApoE-/- mice. Furthermore, these effects might be mediated through the p38 MAPK pathway.

Analysis of Correlation between Gene Polymorphisms of CRHBP in Yunnan Han Population and Schizophrenia and Aggressive Behavior / 法医学杂志

Objective To explore the correlation between 4 tag single nucleotide polymorphisms （Tag SNP） sites （rs7721799, rs32897, rs7718461, rs10062367） of corticotropin releasing hormone binding protein （CRHBP） and schizophrenia and aggressive behavior in the Yunnan Han population. Methods Case-control correlation analysis was used to establish a complex amplification system. Improved multiplex ligase detection reaction （iMLDR） technology was used to detect the genotypes of 4 SNP sites of CRHBP gene of 163 Han schizophrenic patients （including 81 patients with aggressive behavior, 82 patients without aggressive behavior） and 345 healthy Han individuals, which were analyzed statistically by SPSS 19.0, Haploview 4.2 and PHASE 2.1 software. Results There was no correlation between the 3 SNP sites of CRHBP gene and the onset of schizophrenia except for the rs7718461 site （P>0.05）. The relative risk of aggressive behavior of patients carrying GG or GA genotype at rs7718461 site were 4.903 times higher than those carrying AA genotype （P<0.05）. Conclusion The CRHBP gene may not be associated with the occurrence of schizophrenia in Yunnan Han population, but AA genotype of rs7718461 may reduce the risk of aggressive behavior in schizophrenia patients.