Women are less likely to be prescribed statins than men. Existing reports explain only a fraction of this difference. We conducted a study to identify factors that account for sex differences in statin therapy among patients with coronary artery disease (CAD).

Insulin and liraglutide have been demonstrated to control blood glucose and exert neuroprotective effects. However, the impact of liraglutide or insulin alone or in combination on brain pathology in type 1 diabetes mellitus (T1DM) and their underlying mechanisms are unclear. In the present study, diabetes mellitus (DM) was induced via intraperitoneal injection of streptozotocin in mice and subsequently mice were treated with insulin, liraglutide, a combination of the two drugs or saline. Changes in body weight and blood glucose were assessed weekly. The pathological changes in the brain tissue and the apoptosis of neurons were assessed using H&E staining and TUNEL staining. The mRNA and protein expression levels of apoptosis-related proteins were detected using reverse transcription-quantitative PCR (RT-qPCR) and western blotting, respectively. Moreover, Ki67 protein expression was analyzed using immunohistochemistry and the mRNA and protein expression levels of Wnt/β-catenin signaling pathway-related proteins were examined using RT-qPCR and western blotting, respectively. The results of the present study suggested that DM mice developed hyperglycemia and weight loss and also exhibited significantly increased neural cell apoptosis and significantly reduced numbers of Ki67-positive cells. Liraglutide significantly decreased blood glucose levels in DM mice, whereas both insulin and the combination of the two drugs failed to control blood glucose well. Insulin, liraglutide and their combination also failed to control body weight well, but significantly attenuated brain pathological changes and activation of the pro-apoptotic proteins Caspase-3 and Bax, which may have resulted in the significant increase in the expression levels of Wnt/β-catenin signaling pathway-associated molecules such as Wnt3a and S9-pGSK-3β. Liraglutide also promoted the protein expression of the neurogenesis marker of Ki67 and the antiapoptotic factor Bcl-2. These results suggested that insulin and liraglutide may improve brain damage via upregulation of the Wnt/β-catenin signaling pathway and could be of therapeutic relevance for improvement of cognitive impairment in patients with DM.

Healthy adipose tissue is crucial to maintain normal energy homeostasis. Little is known about the role of murine double minute 2 (MDM2), an E3 ubiquitin ligase and has been highlighted in oncopathology, in adipose tissue. Our results indicated that MDM2 expression was associated with nutritional status. Mdm2 adipocyte-specific knock-in (Mdm2-AKI) mice exhibited exacerbated weight gain, insulin resistance, and decreased energy expenditure. Meanwhile, chronic high-fat diet (HFD) exposure caused obvious epididymal white adipose tissue (eWAT) dysfunction, such as senescence, apoptosis, and chronic inflammation, thereby leading to hepatic steatosis in Mdm2-AKI mice. Mechanically, MDM2 could interact with six-transmembrane epithelial antigen of prostate 4 (STEAP4) and inhibit STEAP4 expression through ubiquitin-mediated STEAP4 degradation. Thereinto, the K18 and K161 sites of STEAP4 were ubiquitin-modificated by MDM2. Finally, STEAP4 restoration in eWAT of Mdm2-AKI mice on a HFD rescued MDM2-induced adipose dysfunction, insulin resistance, and hepatic steatosis. Summary, the MDM2-STEAP4 axis in eWAT plays an important role in maintaining healthy adipose tissue function and improving hepatic steatosis.

Colorectal cancer (CRC) is the most common gastrointestinal tumor worldwide, which is a severe malignant disease that threatens mankind. Cathepsin G (CTSG) has been reported to be associated with tumorigenesis, whereas its role in CRC is still unclear. This investigation aims to determine the function of CTSG in CRC. Our results indicated that CTSG was inhibited in CRC tissues, and patients with CTSG low expression have poor overall survival. Functional experiments revealed that CTSG overexpression suppressed CRC cell progression in vitro and in vivo, whereas CTSG suppression supports CRC development cells in vitro and in vivo. Mechanistically, CTSG overexpression suppressed Akt/mTOR signaling mechanism and elevated apoptotic-associated markers, and CTSG silencing activated Akt/mTOR signaling mechanisms and inhibited apoptotic-associated markers. Furthermore, the Akt suppression signaling pathway by MK2206 abolishes CTSG-silenced expression-induced cell viability and Bcl2 up-regulation in vitro and in vivo. Altogether, these outcomes demonstrate that CTSG may act as a tumor suppressor gene via Akt/mTOR/Bcl2-mediated anti-apoptotic signaling inactivation, and CTSG represents a potential therapeutic target in CRC.

Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) gene encodes a transmembrane protein and is involved in multiple physiological and pathological processes, such as inflammatory response, tumor development and progression, cell proliferation and differentiation. A previous study suggested that BAMBI may interact with the Wnt/β-catenin signaling pathway via promoting β-catenin nuclear translocation associated with C2C12 myogenic myoblast differentiation. However, its biological function in skeletal muscle still remains unknown and requires further characterization. The present work sought to investigate its biological function in skeletal muscle, especially the physiological roles of BAMBI during skeletal muscle growth and regeneration. Our current work suggests that BAMBI protein is highly expressed in skeletal muscle and is only detected in cytosolic fraction in the resting muscle. Moreover, BAMBI protein is co-localized in fast-twitch (glycolytic) fibers, but not in slow-twitch (oxidative) fibers. Comparing with the cytosolic trapping in resting muscle, BAMBI protein is enriched on cellular membrane during the muscle growth and regeneration, suggesting that BAMBI-mediated a significant signaling pathway may be an essential part of muscle growth and regeneration.

To investigate the association of polymorphisms in uncoupling protein 2 (UCP2) and peroxisome proliferator-activated receptor (PPARγ) with glucolipid metabolism in Chinese Han population.

Colorectal cancer (CRC) is one of the most common malignant gastrointestinal cancers worldwide. RING finger protein 186 (RNF186) is a member of the RING finger protein family. RNF186 has been reported to be involved in the regulation of the intestinal homeostasis through the regulation of endoplasmic reticulum (ER) stress in colonic epithelial cells. However, its role in CRC remains unclear. In this study, we found that colorectal tumours from human patients had decreased levels of RNF186. We demonstrated that overexpression of RNF186 suppressed the growth and migration of CRC-derived cell lines in vitro and inhibited tumour proliferation in vivo. Further, our findings indicated that forced expression of RNF186 inhibited nuclear factor-κB (NF-κB) activation by reducing the phosphorylation of NF-κB. In addition, our results showed that RNF186-/- mice exhibited significantly increased tumour burden compared to the wild type (WT) mice following treatment with azoxymethane/dextran sulfate sodium (AOM/DSS). Compared to WT mice, the percentage of Ki67 positive cells was increased in the RNF186-/- mice, indicating that RNF186 is crucial for intestinal cell proliferation during tumorigenesis. Taken together, our data suggest that RNF186 inhibits the development of CRC, and that this effect is mediated through the suppression of NF-κB activity.

Artificial intelligence (AI) technology is widely applied in different medical fields, including the diagnosis of various diseases on the basis of facial phenotypes, but there is no evaluation or quantitative synthesis regarding the performance of artificial intelligence. Here, for the first time, we summarized and quantitatively analyzed studies on the diagnosis of heterogeneous diseases on the basis on facial features. In pooled data from 20 systematically identified studies involving 7 single diseases and 12,557 subjects, quantitative random-effects models revealed a pooled sensitivity of 89% (95% CI 82% to 93%) and a pooled specificity of 92% (95% CI 87% to 95%). A new index, the facial recognition intensity (FRI), was established to describe the complexity of the association of diseases with facial phenotypes. Meta-regression revealed the important contribution of FRI to heterogeneous diagnostic accuracy (p = 0.021), and a similar result was found in subgroup analyses (p = 0.003). An appropriate increase in the training size and the use of deep learning models helped to improve the diagnostic accuracy for diseases with low FRI, although no statistically significant association was found between accuracy and photographic resolution, training size, AI architecture, and number of diseases. In addition, a novel hypothesis is proposed for universal rules in AI performance, providing a new idea that could be explored in other AI applications.

Colorectal cancer (CRC) is a malignant disease that is a serious threat to human health. Rutaecarpine (RUT) is an important bioactive alkaloid of Evodia rutaecarpa. According to previous studies, RUT suppressed the proliferation of several human tumors. However, its role in colorectal tumorigenesis remained unknown. The aim of the present study was to determine the functions of RUT in CRC. Here, we have demonstrated that RUT inhibited the proliferation, migration and invasion of CRC cells in vitro. Further, RUT was found to induce the apoptosis of CRC cells. Mechanistically, RUT decreased the phosphorylation levels of NF-κB and STAT3. Moreover, treatment with RUT upregulated the expression of cleaved-Caspase3 and downregulated the expression of Bcl-2 in CRC. In addition, our findings suggested that RUT inhibited the growth and lung metastasis of CRC Cells in vivo. Based on immunofluorescence analysis, the expression of Ki67 was downregulated while that of cleaved-Caspase3 was upregulated in RUT-treated tumors compared with control-treated tumors. Taken together, our findings indicate that RUT can inhibit the proliferation and migration of CRC cells, and induce the apoptosis of CRC cells by inactivating NF-κB/STAT3 signaling. Our study highlights the potential clinical application of RUT for the treatment of CRC.

Cellular aging markers, including telomere length and mitochondrial function, as well as oxidative stress and inflammation markers influence each other and form a complex network, which is affected in diabetes. However, it remains unknown whether these markers could independently predict future diabetes after adjustment for their mutual effects. We conducted a 3-year longitudinal study in a Chinese cohort that comprised 108 nondiabetic individuals at baseline. The 2-hour 75 g oral glucose tolerance tests were performed at baseline and at 3-year follow-up. At baseline, leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn) in leukocytes were determined using the polymerase chain reaction method. Tumor necrosis factor (TNF-α), interleukin-6, 8-hydroxy-2-deoxyguanosine levels, and superoxide dismutase (SOD) activity were measured by the enzyme-linked immunosorbent assay. Participants who developed diabetes at the 3-year follow-up (n = 28) had shorter LTL and higher levels of TNF-α and SOD activity at baseline. Baseline LTL was found to be independently associated with the development of diabetes at the 3-year follow-up after the adjustment for mtDNAcn, markers of oxidative stress and inflammation, and conventional diabetes risk factors. Our findings suggest that LTL is an independent predictor for 3-year diabetes risk, which might inform timely prevention and treatment of diabetes. Telomere shortening might be involved in the pathogenesis of diabetes independently of conventional diabetes risk factors, mtDNAcn, or oxidative stress and inflammation pathways.

Type B insulin resistance syndrome (TBIRS) is a rare condition, for which effective treatment remains challenging.

Background: T cells are crucial components of antitumor immunity. A list of genes associated with T cell proliferation was recently identified; however, the impact of T cell proliferation-related genes (TRGs) on the prognosis and therapeutic responses of patients with colorectal cancer (CRC) remains unclear. Methods: 33 TRG expression information and clinical information of patients with CRC gathered from multiple datasets were subjected to bioinformatic analysis. Consensus clustering was used to determine the molecular subtypes associated with T cell proliferation. Utilizing the Lasso-Cox regression, a predictive signature was created and verified in external cohorts. A tumor immune environment analysis was conducted, and potential biomarkers and therapeutic drugs were identified and confirmed via in vitro and in vivo studies. Results: CRC patients were separated into two TRG clusters, and differentially expressed genes (DEGs) were identified. Patient information was divided into three different gene clusters, and the determined molecular subtypes were linked to patient survival, immune cells, and immune functions. Prognosis-associated DEGs in the three gene clusters were used to evaluate the risk score, and a predictive signature was developed. The ability of the risk score to predict patient survival and treatment response has been successfully validated using multiple datasets. To discover more possible biomarkers for CRC, the weighted gene co-expression network analysis algorithm was utilized to screen key TRG variations between groups with high- and low-risk. CDK1, BATF, IL1RN, and ITM2A were screened out as key TRGs, and the expression of key TRGs was confirmed using real-time reverse transcription polymerase chain reaction. According to the key TRGs, 7,8-benzoflavone was identified as the most significant drug molecule, and MTT, colony formation, wound healing, transwell assays, and in vivo experiments indicated that 7,8-benzoflavone significantly suppressed the proliferation and migration of CRC cells. Conclusion: T cell proliferation-based molecular subtypes and predictive signatures can be utilized to anticipate patient results, immunological landscape, and treatment response in CRC. Novel biomarker candidates and potential therapeutic drugs for CRC were identified and verified using in vitro and in vivo tests.

Sirtuin 3 (SIRT3) is one of the seven mammalian sirtuins, which are homologs of the yeast Sir2 gene. SIRT3 is the only sirtuin with a reported association with the human life span. Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) plays important roles in adaptive thermogenesis, gluconeogenesis, mitochondrial biogenesis and respiration. PGC-1alpha induces several key reactive oxygen species (ROS)-detoxifying enzymes, but the molecular mechanism underlying this is not well understood.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder strongly associated with hepatic glucose intolerance and insulin resistance. The trefoil peptides are a family of small regulatory proteins and Tff3 is widely expressed in multiple tissues including liver. But the roles of Tff3 in regulation of glucose metabolism and insulin sensitivity in liver remain unclear. Here we show that the hepatic Tff3 expression levels were decreased in ob/ob and high-fat diet-induced obese mice. Overexpression of Tff3 in primary mouse hepatocytes inhibited the expression of gluconeogenic genes, including G6pc, PEPCK and PGC-1α, subsequently decreasing cellular glucose output. GTT and ITT experiments revealed that adenovirus-mediated overexpression of Tff3 in diabetic or obese mice improved glucose tolerance and insulin sensitivity. Collectively, our results indicated that Tff3 peptides are involved in glucose homeostasis and insulin sensitivity, providing a promising peptide on new therapies against the metabolic disorders associated with T2DM.

In China, TianMai Xiaoke tablet (TM) is used to treat type 2 diabetes. However, the exact mechanism of TM is not clear. This study is to investigate the effect of TM on glucose metabolism in diabetic rats and to identify whether TM takes a direct action through microRNAs on islet. Rats were divided into control group, diabetic group, low dose of TM group (TML), and high dose of TM group (TMH). Pancreas samples were analyzed using microRNA array and Q-PCR. Eight-week treatment with TM significantly decreased fasting blood glucose. The blood glucose was significantly reduced in TM-treated groups before and after oral glucose administration. Fasting insulin and HOMA-IR were suppressed in TM-treated groups. miR-448, let-7b, miR-540, miR-296, miR-880, miR-200a, miR-500, miR-10b, miR-336, miR-30d, miR-208, let-7e, miR-142-5p, miR-874, miR-375, miR-879, miR-501, and miR-188 were upregulated, while miR-301b, miR-134, and miR-652 were downregulated in TMH group. Through target gene analysis and real-time PCR verification, we found that these miRNAs, especially miR-375 and miR-30d, can stimulate insulin secretion in islet. Our data suggest that TM can improve blood glucose in diabetic rats which involved increasing the expression of miR-375 and miR-30d to activate insulin synthesis in islet.

We aimed to investigate the associations of flash glucose monitoring (FGM)-derived metrics with lipid profiles and identify potential modifiers of these associations among adults with type 1 diabetes (T1D).

To examine the association between dipeptidyl peptidase-4 inhibitors and gallbladder or biliary diseases.

Background: Cellular senescence is a typical irreversible form of life stagnation, and recent studies have suggested that long non-coding ribonucleic acids (lncRNA) regulate the occurrence and development of various tumors. In the present study, we attempted to construct a novel signature for predicting the survival of patients with hepatocellular carcinoma (HCC) and the associated immune landscape based on senescence-related (sr) lncRNAs. Method: Expression profiles of srlncRNAs in 424 patients with HCC were retrieved from The Cancer Genome Atlas database. Lasso and Cox regression analyses were performed to identify differentially expressed lncRNAs related to senescence. The prediction efficiency of the signature was checked using a receiver operating characteristic (ROC) curve, Kaplan-Meier analysis, Cox regression analyses, nomogram, and calibration. The risk groups of the gene set enrichment analysis, immune analysis, and prediction of the half-maximal inhibitory concentration (IC50) were also analyzed. Quantitative real-time polymerase chain reaction (qPCR) was used to confirm the levels of AC026412.3, AL451069.3, and AL031985.3 in normal hepatic and HCC cell lines. Results: We identified 3 srlncRNAs (AC026412.3, AL451069.3, and AL031985.3) and constructed a new risk model. The results of the ROC curve and Kaplan-Meier analysis suggested that it was concordant with the prediction. Furthermore, a nomogram model was constructed to accurately predict patient prognosis. The risk score also correlated with immune cell infiltration status, immune checkpoint expression, and chemosensitivity. The results of qPCR revealed that AC026412.3 and AL451069.3 were significantly upregulated in hepatoma cell lines. Conclusion: The novel srlncRNA (AC026412.3, AL451069.3, and AL031985.3) signatures may provide insights into new therapies and prognosis predictions for patients with HCC.

Mutations in the glucokinase gene (GCK) are a pathogenetic cause of maturity-onset diabetes of the young. Studies have found that female patients with GCK maturity-onset diabetes of the young often present with gestational diabetes during pregnancy. Our aim was to preliminarily assess the prevalence of mutations in the glucokinase gene in Chinese women with gestational diabetes.

The cardiovascular efficacy of glucagon-like peptide 1 receptor agonists (GLP-1RAs) in type 2 diabetes mellitus (T2DM) are well documented; however, the differences in cardiovascular efficacy among subpopulations remain unknown. This systematic review and meta-analysis aimed to explore the differences in cardiovascular efficacy of long-acting GLP-1RAs among subpopulations of patients with T2DM and to assess the drug safety.