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Abstract The inhibitor of apoptosis protein survivin has a critical regulatory role in carcinogenesis and treatment tolerance in colorectal cancer (CRC). However, the targeted drugs for survivin protein are extremely limited. In the present research, we discovered that Tanshinone IIA (Tan IIA) played a dual regulatory role in inhibiting tumorigenesis and reversing 5-Fu tolerance via modulating the expression and phosphorylation of survivin in CRC cells. Mechanistically, Tan IIA suppressed the Akt/WEE1/CDK1 signaling pathway, which led to the downregulation of survivin Thr34 phosphorylation and destruction of the interaction between USP1 and survivin to promote survivin ubiquitination and degradation. Furthermore, Tan IIA significantly facilitated chemoresistant CRC cells to 5-Fu sensitivity. These results revealed that Tan IIA possessed a strong antitumor activity against CRC cells and could act as an up-and-coming agent for treating CRC and overcoming chemotherapy resistance.

Abstract. Background:. Management of gastric leak after sleeve gastrectomy (SG) is challenging due to its unpredictable outcomes. We aimed to summarize the characteristics of SG leaks and analyze interventions and corresponding outcomes in a real-world setting. Methods:. To retrospectively review of 15,721 SG procedures from 2010 to 2020 based on a national registry. A cumulative sum analysis was used to identify a fitting curve of gastric leak rate. The Kaplan-Meier method and log-rank tests were performed to calculate and compare the probabilities of relevant outcomes. The logistic regression analysis was conducted to determine the predictors of acute leaks. Results:. A total of 78 cases of SG leaks were collected with an incidence of 0.5% (78/15,721) from this registry (6 patients who had the primary SG in non-participating centers). After accumulating 260 cases in a bariatric surgery center, the leak rate decreased to a stably low value of under 1.17%. The significant differences presented in sex, waist circumference, and the proportion of hypoproteinemia and type 2 diabetes at baseline between patients with SG leak and the whole registry population (P = 0.005, = 0.026, 50%, whereas the cumulative healing probability in the patients who required surgical treatment was significantly lower than those requring non-surgical treatment (P = 0.013). Precise dissection in the His angle area was independently associated with a lower acute leak rate, whereas preservation ≥2 cm distance from the His angle area was an independent risk factor. Conclusions:. Male sex, elevated waist circumference, hypoproteinaemia, and type 2 diabetes are risk factors of gastric leaks after SG. Optimizing surgical techniques, including precise dissection of His angle area and preservation of smaller gastric fundus, should be suggested to prevent acute leaks.

Vaccinium duclouxii, a wild blueberry species native to the mountainous regions of southwestern China, is notable for its exceptionally high anthocyanin content, surpassing that of many cultivated varieties and offering significant research potential. Glutathione S-transferases (GSTs) are versatile enzymes crucial for anthocyanin transport in plants. Yet, the GST gene family had not been previously identified in V. duclouxii. This study utilized a genome-wide approach to identify and characterize the GST gene family in V. duclouxii, revealing 88 GST genes grouped into seven distinct subfamilies. This number is significantly higher than that found in closely related species, with these genes distributed across 12 chromosomes and exhibiting gene clustering. A total of 46 members are classified as tandem duplicates. The gene structure of VdGST is relatively conserved among related species, showing closer phylogenetic relations to V. bracteatum and evidence of purifying selection. Transcriptomic analysis and qRT-PCR indicated that VdGSTU22 and VdGSTU38 were highly expressed in flowers, VdGSTU29 in leaves, and VdGSTF11 showed significant expression in ripe and fully mature fruits, paralleling trends seen with anthocyanin accumulation. Subcellular localization identified VdGSTF11 primarily in the plasma membrane, suggesting a potential role in anthocyanin accumulation in V. duclouxii fruits. This study provides a foundational basis for further molecular-level functional analysis of the transport and accumulation of anthocyanins in V. duclouxii, enhancing our understanding of the molecular mechanisms underlying anthocyanin metabolism in this valuable species.

Abstract Background Conflicting results on the prognostic value of the visceral adiposity index (VAI) in patients with metabolic-associated fatty liver disease (MAFLD) have been reported. This study aimed to assess the diagnostic value of the VAI in MAFLD patients. Methods The Cochrane Library, PubMed, Embase, and other databases were searched to collect all documents that met the inclusion criteria from the establishment of the database to September 2021. The methodological quality of the included studies was assessed using the Newcastle–Ottawa Scale. The heterogeneity among the studies was analysed by the Cochran Q test and I2 test, and the appropriate model was selected according to the heterogeneity results. The diagnostic efficacy of the VAI was evaluated by sensitivity, specificity, and area under the curve, and a Fagan diagram was generated to evaluate the diagnostic ability of the VAI. Results A total of 9 studies were included. The overall quality of the included studies was good. Meta-analysis showed that the combined sensitivity of the VAI for the diagnosis of MAFLD was 0.70 [95% CI (0.69–0.71)], the combined specificity was 0.67 [95% CI (0.67–0.68)], the combined positive likelihood ratio was 2.08 [95% CI (1.87–2.31)], the combined negative likelihood ratio was 0.39 [95% CI (0.34–0.44)], and the combined diagnostic odds ratio was 5.81 [95% CI (4.73–7.14)]. The corresponding area under the curve was 0.79 [95% CI (0.75–0.82)]. Meta-regression analysis showed that the diagnostic method was a potential source of heterogeneity (P 2.33 suggests that patients have a high probability of having MAFLD.

Abstract Colorectal cancer (CRC) is one of the most common cancers worldwide and a leading cause of carcinogenic death. To date, surgical resection is regarded as the gold standard by the operator for clinical decisions. Because conventional tissue biopsy is invasive and only a small sample can sometimes be obtained, it is unable to represent the heterogeneity of tumor or dynamically monitor tumor progression. Therefore, there is an urgent need to find a new minimally invasive or noninvasive diagnostic strategy to detect CRC at an early stage and monitor CRC recurrence. Over the past years, a new diagnostic concept called “liquid biopsy” has gained much attention. Liquid biopsy is noninvasive, allowing repeated analysis and real-time monitoring of tumor recurrence, metastasis or therapeutic responses. With the advanced development of new molecular techniques in CRC, circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), exosomes, and tumor-educated platelet (TEP) detection have achieved interesting and inspiring results as the most prominent liquid biopsy markers. In this review, we focused on some clinical applications of CTCs, ctDNA, exosomes and TEPs and discuss promising future applications to solve unmet clinical needs in CRC patients.

BackgroundThe impact of screen time on mental health, including depression, has attracted increasing attention from not only children and adolescents but also the elderly. Thus, we conducted a meta-analysis of cohort studies to evaluate the association between screen time and depression risk.MethodsThe PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases were searched for cohort studies up to May 2022, and the reference lists of the included studies were also retrieved. A random-effect model was used to estimate the combined effect size. Heterogeneity was assessed with the I2 statistic. Potential publication bias was evaluated using a funnel plot and Begg’s and Egger’s tests.ResultsThe final analysis included 18 cohort studies with a combined total of 241,398 participants. The pooled risk ratio (RR) was 1.10 (95% confidence interval: 1.05–1.14), with significant heterogeneity (I2 = 82.7%, P < 0.001). The results of subgroup analyses showed that the pooled RRs varied according to geographic locations, gender, age group, screen time in the control group, depression at the baseline, and whether the study was conducted during the COVID-19 pandemic. No obvious evidence of publication bias was found.ConclusionThis study indicates that screen time is a predictor of depressive symptoms. The effects of screen time on depression risk may vary based on the participant’s age, gender, location, and screen time duration. The findings could have important implications for the prevention of depression.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is associated with obesity and insulin resistance and can be improved after bariatric surgery. Circulating Peroxiredoxin 1 (Prdx1) protein was reported to regulate energy metabolism and inflammation. This study aimed to investigate the roles of serum prdx1 in NAFLD patients with obesity undergoing LSG and to develop a prognostic model to predict the remission of severe NAFLD.MethodsThe data of 93 participants from a tertiary hospital were assessed. Before laparoscopic sleeve gastrectomy (LSG) and three months after LSG, anthropometric parameters, laboratory biochemical data, and abdominal B-ultrasound results were collected, and their hepatic steatosis index (HSI) and triglyceride-glucose index (TyG) were calculated. A NAFLD improvement (NAFLD-I) nomogram prediction model was constructed using the least absolute shrinkage and selection operator (LASSO) regression and multiple regression, and its predictive ability was verified in a validation cohort.ResultsThe baseline Prdx1 (OR: 0.887, 95% CI: 0.816-0.963, p=0.004), preoperative TyG (OR: 8.207, 95% CI: 1.903-35.394, p=0.005) and HSI (OR: 0.861, 95% CI: 0.765-0.969, p=0.013) levels were independently associated with NAFLD-I at three months after LSG in NAFLD patients with obesity. In the primary and validation cohorts, the area under the receiver operating characteristic (AUC) of the developed nomogram model was 0.891 and 0.878, respectively. The preoperative circulating Prdx1 levels of NAFLD patients with obesity were significantly reduced after LSG (25.32 [18.99-30.88] vs. 23.34 [15.86-26.42], p=0.001). Prdx1 was related to obesity and hepatic steatosis based on correlation analysis.ConclusionThe nomogram based on preoperative serum prdx1, HSI and TyG could be an effective tool for predicting remission of severe NAFLD after LSG.

BackgroundThe relationship between daytime napping and depression remains debatable. Thus, a meta-analysis in this study was conducted to evaluate the relationship between daytime napping and depression.MethodsThe PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases were searched up to February 2022, and the reference lists of the included studies were also retrieved. A random-effects model was used to estimate the combined effect size.ResultsNine studies with 649,111 participants were included in the final analysis. The pooled odds ratio (OR) was 1.15 (95% confidence interval: 1.01–1.31) with a significant heterogeneity (I2 = 91.3%, P for heterogeneity

BackgroundObesity is associated with polycystic ovary syndrome (PCOS). We aimed to elucidate the research status and explore research trends and future directions of research on obesity and PCOS.MethodsA bibliometric analysis of the published papers in the field of obesity and PCOS between 2012 and 2022 was conducted on the basis of the Web of Science Core Collection database. The collaboration networks, research trends, literature sources, citation analysis, co-citation analysis, and keywords analysis were statistically analyzed and visualized using the VOSviewer software.ResultsWe retrieved 2843 records from 681 journals by 12307 authors from 2942 institutes in 99 countries. The number of published papers and citations had a roughly increasing trend annually. The United States and China contributed the majority of the records. Monash University, Shanghai Jiaotong University, Aristotle University of Thessaloniki, Karolinska Institute, University of São Paulo, and Tehran University of Medical Sciences were the biggest nodes in their cluster of the collaboration network map, and Moran LJ, Teede HJ, Joham AE, Escobar-Morreale HF, and Macut D were prolific authors. Research trends and hotspots were identified and visualized in the field of obesity and PCOS. Research hotspots in this field focused on insulin resistance (IR), metabolic syndrome, metformin, and inflammation. Bariatric surgery, mitochondrial dysfunction, binding globulins, and comorbidities may be the frontiers of future research.ConclusionsWe concluded the research status and trends in the field of obesity and PCOS. A better understanding of collaboration patterns, research hotspots, and frontiers may be useful for researchers.

BackgroundEmerging evidence supported the significant role of body composition and fat distribution in the etiology and pathogenesis of Type 2 diabetes mellitus (T2DM).ObjectiveTo assess the predictive value of representative parameters of body composition and fat distribution for T2DM remission after bariatric surgery.MethodsA total of 72 patients with T2DM who underwent bariatric surgery in our center between September 2010 and December 2018 were included in this retrospective observational study. Diabetes remission was defined according to the American Diabetes Association criteria released in 2021. Body fat percentage, skeletal muscle index, Android/Gynoid ratio and trunk/leg fat ratio were derived from dual-energy X-ray absorptiometry and assessed.ResultsA total of 40 patients (56%) achieved remission among 72 patients. Patients in the remission group had higher body fat percentage and lower trunk/leg fat ratio than those in the non-remission group. The area under the receiver operating characteristic curve (AUC) for predicting T2DM remission was higher for trunk/leg fat ratio (0.784), compared to BMI (AUC 0. 0.690) and body fat percentage (AUC 0.688). The prediction model (AUC 0.883) including age, duration of T2DM, and trunk/leg fat ratio performed better than the ABCD score (AUC 0.809) and the DiaRem score (AUC 0.792). A nonlinear relationship was observed between trunk/leg fat ratio and BMI.ConclusionTrunk/leg fat ratio is a promising predictor for T2DM remission after bariatric surgery.

BackgroundRoux-en-Y gastric bypass (RYGB) results in extraordinary weight loss and glycemic control outcomes for patients with obesity; however, the effect of gastric pouch size is still unclear, and the reported results are contradictory. Additionally, long-term data on type 2 diabetes (T2D) patients with low body mass index (BMI) are sparse. This study was to assess the effect of 6-year outcomes in Chinese patients with T2D and a BMI < 35 kg/m2 who underwent RYGB with gastric pouches of different sizes.MethodsA retrospective cohort study was performed. There were 42 patients in the large gastric pouch group (L) and 53 patients in the small gastric pouch group (S). Baseline demographic history, pre- and postoperative BMI, waist circumference, and glucose- and lipid metabolism-related indicators were compared.ResultsAssessments were completed in 100%, 100%, 93.6%, and 89.4% of patients at baseline, 1 year, 3 years, and 6 years, respectively. At 6 years, the changes in BMI and fasting plasma glucose were greater in the S group (-4.25 ± 0.51 kg/m2 and -4.58 ± 0.73 mmol/l) than in the L group (-2.06 ± 0.48 kg/m2 and -2.64 ± 0.61 mmol/l). The independent predictors of complete remission of T2D were preoperative BMI and the size of the gastric pouch. A large gastric pouch was associated with a higher risk for marginal ulcers.ConclusionsA small gastric pouch results in better weight loss and glycemic control. High preoperative BMI and a small gastric pouch are associated with better T2D remission rates. A large gastric pouch leads to a higher incidence of marginal ulcers.

Natural pyrethrins have high application value, and are widely used as a green pesticide in crop pest prevention and control. Pyrethrins are mainly extracted from the flower heads of Tanacetum cinerariifolium; however, the natural content is low. Therefore, it is essential to understand the regulatory mechanisms underlying the synthesis of pyrethrins through identification of key transcription factors. We identified a gene encoding a MYC2-like transcription factor named TcbHLH14 from T. cinerariifolium transcriptome, which is induced by methyl jasmonate. In the present study, we evaluated the regulatory effects and mechanisms of TcbHLH14 using expression analysis, a yeast one-hybrid assay, electrophoretic mobility shift assay, and overexpression/virus-induced gene silencing experiments. We found that TcbHLH14 can directly bind to the cis-elements of the pyrethrins synthesis genes TcAOC and TcGLIP to activate their expression. The transient overexpression of TcbHLH14 enhanced expression of the TcAOC and TcGLIP genes. Conversely, transient silencing of TcbHLH14 downregulated the expression of TcAOC and TcGLIP and reduced the content of pyrethrins. In summary, these results indicate that the potential application of TcbHLH14 in improving the germplasm resources and provide a new insight into the regulatory network of pyrethrins biosynthesis of T. cinerariifolium to further inform the development of engineering strategies for increasing pyrethrins contents.

Abstract Background A new device has been added to the Chinese MicroHand surgical robot family, developed based on the successful application of control algorithms. As a benefit of using these specialized control algorithms, the motion mapping relation can be accommodated into the system without the help of a built-in image system, resulting in a novel Chinese domestic surgical robot with two arms called MicroHand SII, which is different from the former MicroHand S and da Vinci systems. In this study, we investigate the performance of a novel MicroHand SII robotic platform in patients with obesity. Methods From March 2018 to April 2019, a total of 7 patients whose BMI ranged from 29.9 to 49.8 kg/m2 were operated on with the robot-assisted technique using the MicroHand SII surgical system. Data regarding demography, surgical procedure and the 3-month outcome postoperation were collected. Results There were 2 female and 5 male patients with a median age (range) of 35 (20–51) years. The median operative time was 160 (149–195) minutes. None were converted to open surgery. All anthropometry indices improved significantly (p

Abstract The period circadian regulator 3 (PER3) has been reported to play a negative role in human immortalized bone marrow-derived Scp-1 cells (iBMSCs) and patient adipose-derived stromal cells (PASCs) or a negative/positive role in mice adipogenesis. However, human PER3 (hPER3) was identified as a positive regulator of human adipose tissue-derived stromal cells (hADSCs) adipogenesis in this study. Silencing or overexpression of hPER3 in hADSCs inhibited and promoted adipogenesis in vitro. In vivo, the overexpression of hPER3 increased high-fat diet-induced inguinal white adipose tissue (iWAT) and epididymal white adipose tissue (eWAT) forms, increasing systemic glucose intolerance and insulin resistance. Molecularly, hPER3 does not interact with hPPARγ, but represses Notch1 signaling pathway to enhance adipogenesis by interacting with hHSP90AA1, which is able to combine with the promoter of hNotch1 and inactivate its expression. Thus, our study revealed hPER3 as a critical positive regulator of hADSCs adipogenesis, which was different from the other types of cells, providing a critical role of it in treating obesity.

Aims: Current idiopathic pulmonary fibrosis (IPF) therapies usually show a poor outcome or treatment efficacy. The search for new risk factors has significant implications in preventing, delaying, and treating IPF. The association between obesity and the risk of IPF is not clear. This study aimed to investigate the role of different obesity types in IPF risk, which provides the possibility of weight loss as a new approach for IPF prevention.Methods: We conducted a two-sample Mendelian randomization (MR) analysis to assess the causal effect of obesity on IPF risk. We collected summary data of genetically determined obesity-related traits, including body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) from large-scale consortia (the sample size ranging from 232,101 to 681,275), and genetic association with IPF from one of the largest meta-analyses including 2,668 cases. A total of 35–469 single nucleotide polymorphisms were selected as instrumental variables for obesity-related traits. We further performed multivariable MR to estimate the independent effect of BMI and WC on the risk of IPF.Results: Increased BMI and WC were associated with higher risk of IPF [odds ratio (OR) = 1.51, 95% confidence interval (CI) (1.22–1.87), p = 1.27 × 10–4, and OR = 1.71, 95% CI (1.08–2.72), p = 2.33 × 10–2, respectively]. Similar results for the BMI and WC were obtained in the replicated analysis. Subsequently, only the result for BMI survived following the multiple testing correction and showed good consistency with the weighted median estimator. Sensitivity analyses indicated that there was no heterogeneity or horizontal pleiotropy for MR estimations. Further multivariable MR suggested that the BMI showed the same direction and similar magnitude with that in the univariable MR analysis. There was little evidence to support the causal role of WHR on the risk of IPF in this study.Conclusion: Genetically determined BMI demonstrates a causal risk for IPF, which offers a novel insight into probing potential mechanisms. Meanwhile, these results also suggest that weight loss may be beneficial to IPF prevention.

Background: Insulin resistance (IR) is closely associated with the pathogenesis of type 2 diabetes mellitus (T2DM). However, remission of insulin sensitivity after bariatric surgery in patients with T2DM and a body mass index (BMI) of 27.5–32.5 kg/m2 has not been fully elucidated.Methods: Thirty-six T2DM patients with a BMI of 27.5–32.5 kg/m2 were prospectively consecutively recruited for laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG). Hyperinsulinemic euglycemic clamp, oral glucose tolerance test (OGTT), and other indicators were tested at baseline and 6 months postoperative. Glucose disposal rate (GDR), time to reach euglycemia, homeostatic model assessment of IR, quantitative insulin sensitivity check index (QUICKI), triglyceride glucose (TyG) index, 30-min insulinogenic index (IGI30), and disposition index (DI) were calculated at baseline and 6 months after surgery. The criterion for remission in T2DM patients was the achievement of the triple composite endpoint.Results: Anthropometric and glucolipid metabolism parameters significantly improved following surgery. The GDR increased significantly from baseline to 6 months after LRYGB (from 4.28 ± 1.70 mg/kg/min to 8.47 ± 1.89 mg/kg/min, p < 0.0001) and LSG (from 3.18 ± 1.36 mg/kg/min to 7.09 ± 1.69 mg/kg/min, p < 0.001). The TyG index decreased after surgery (RYGB group, from 9.93 ± 1.03 to 8.60 ± 0.43, p < 0.0001; LSG group, from 10.04 ± 0.79 to 8.72 ± 0.65, p = 0.0002). There was a significant reduction in the IGI30 (RYGB group, from 2.04 ± 2.12 to 0.83 ± 0.47, p = 0.005; LSG group, from 2.12 ± 1.73 to 0.92 ± 0.66, p = 0.001). The mean DI significantly increased from 1.14 ± 1.35 to 7.11 ± 4.93 in the RYGB group (p = 0.0001) and from 1.25 ± 1.78 to 5.60 ± 4.58 in the LSG group (p = 0.003). Compared with baseline, HOMR-IR, QUICKI, area under the curve-C-peptide release test (AUC-CRT), and AUC-OGTT were significantly changed at 6 months postoperative. Overall, 52.63% of patients in the LRYGB group versus 29.41% of patients in the LSG group achieved the triple composite endpoint.Conclusion: Both LRYGB and LSG effectively induced remission of IR in patients with T2DM and a BMI of 27.5–32.5 kg/m2.

T2DM (Type 2 diabetes) is a complex, chronic disease characterized as insulin resistance and islet β-cell dysfunction. Bariatric surgeries such as Roux-en-Y gastric bypass (RYGB) surgery and laparoscopic sleeve gastrectomy (LSG) have become part of a critical treatment regimen in the treatment of obesity and T2DM. Moreover, GLP-1 increase following bariatric surgery has been regarded as a significant event in bariatric surgery-induced remission of T2DM. In this study, a high concentration cholesterol-induced lipotoxicity was observed in INS-1 cells, including inhibited cell viability and insulin secretion. Enhanced cell apoptosis and inhibited cholesterol efflux from INS-1 cells; meanwhile, ABCA1 protein level was decreased by cholesterol stimulation. Cholesterol-induced toxicity and ABCA1 downregulation were attenuated by GLP-1 agonist EX-4. GLP-1 induced AMPK phosphorylation during the protection against cholesterol-induced toxicity. Under cholesterol stimulation, GLP-1-induced AMPK activation inhibited PARP-1 activity, therefore attenuating cholesterol-induced toxicity in INS-1 cells. In INS-1 cells, PARP-1 directly interacted with LXR, leading to the poly(ADP-ribosyl)ation of LXRα and downregulation of LXR-mediated ABCA1 expression. In the STZ-induced T2DM model in rats, RYGB surgery or EX-4 treatment improved the glucose metabolism and lipid metabolism in rats through GLP-1 inhibition of PARP-1 activity. In conclusion, GLP-1 inhibits PARP-1 to protect islet β cell function against cholesterol-induced toxicity in vitro and in vivo through enhancing cholesterol efflux. GLP-1-induced AMPK and LXR-mediated ABCA1 expression are involved in GLP-1 protective effects.

Diabetes is a metabolic disorder induced by the modulation of insulin on glucose metabolism, and the dysfunction and decreased number of islets β-cells are the main causes of T2DM (type 2 diabetes mellitus). Among multiple factors that might participate in T2DM pathogenesis, the critical roles of miRNAs in T2DM and β-cell dysfunction have been reported. Through bioinformatics analyses and literature review, we found that miR-344 might play a role in the occurrence and progression of diabetes in rats. The expression levels of miR-344-5p were dramatically decreased within cholesterol-stimulated and palmitic acid (PA)-induced rats’ islet β-cells. In cholesterol-stimulated and PA-induced diabetic β-cell model, cholesterol-caused and PA-caused suppression on cell viability, increase in intracellular cholesterol level, decrease in GSIS, and increase in lip droplet deposition were dramatically attenuated via the overexpression of miR-344-5p, whereas aggravated via the inhibition of miR-344-5p. miR-344-5p also inhibited cholesterol-induced β-cell death via affecting the apoptotic caspase 3/Bax signaling. Insulin receptor downstream MPAK/ERK signaling was involved in the protection of miR-344-5p against cholesterol-induced pancreatic β-cell dysfunction. Moreover, miR-344-5p directly targeted Cav1; Cav1 silencing could partially reverse the functions of miR-344-5p inhibition upon cholesterol-induced β-cell dysfunction, β-cell apoptosis, the apoptotic caspase 3/Bax signaling, and insulin receptor downstream MPAK/ERK signaling. In conclusion, the miR-344-5p/Cav1 axis modulates cholesterol-induced β-cell apoptosis and dysfunction. The apoptotic caspase 3/Bax signaling and MAPK/ERK signaling might be involved.

Omeprazole is commonly prescribed to obese patients and patients after laparoscopic sleeve gastrectomy (LSG). The pharmacokinetics of oral omeprazole after LSG are still unknown. Therefore, the aim of this study was to investigate the pharmacokinetics of oral omeprazole in obese patients before and after LSG. A total of 331 blood samples were collected from 62 obese patients preoperatively (visit 1) followed by 41 patients 7 days post-LSG (visit 2) and 20 patients 1 month post-LSG (visit 3). Population pharmacokinetic analysis was performed using NONMEM to characterize the effect of LSG on omeprazole absorption and disposition. A one-compartment model with 12 transit absorption compartments and linear elimination successfully described the data. Compared with pre-surgery, the oral omeprazole time to maximum plasma concentration (Tmax) was reduced and maximum plasma concentration (Cmax) was higher, but the apparent clearance (CL/F) and area under the plasma concentration–time curve (AUC) were unchanged 7 days and 1 month after surgery. In addition, the CYP2C19 genotype and liver function exhibited a significant influence on omeprazole CL/F. LSG increased the rate of omeprazole absorption but did not affect omeprazole exposure. A dose of 20 mg omeprazole once daily may be adequate for relieving gastrointestinal tract discomfort at short-term follow-up post-LSG.

Background and objectives: Chinese type 2 diabetes mellitus (T2DM) patients are characterized by a low body mass index (BMI), and significant insulin resistance (IR). The triglyceride glucose (TyG) index has not been studied as a means of assessing IR in Chinese T2DM patients with a BMI < 35 kg/m2. Materials and Methods: An open-label cross-sectional study recruited 102 Chinese T2DM patients with a BMI < 35 kg/m2. The hyper-insulinemic euglycemic clamp, homeostatic model assessment of IR (HOMA-IR), and TyG index were used to determine the level of IR. Based on Pearson’s correlations, glucose disposal rate (GDR), TyG index, and HOMA-IR were analyzed. HOMA-IR and TyG index for IR were evaluated using multiple linear regression and multivariate logistic regression analyses. On the basis of the receiver operating characteristic (ROC) curve, the sensitivity, specificity, and optimal cut-off value of HOMA-IR and the TyG index were determined. Results: The mean values of GDR, HOMA-IR, and TyG index were 4.25 ± 1.81, 8.05 ± 7.98, and 8.12 ± 0.86 mg/kg/min, respectively. Pearson’s correlation coefficient was −0.418 between GDR and TyG index and −0.324 between GDR and HOMA-IR. ROC curve analysis showed that, among both sexes, the TyG index was a better discriminator of IR than HOMA-IR. The area under the ROC curve (AUC) of the TyG index (0.785, 0.691–0.879) was higher than that of HOMA-IR (0.73, 0.588–0.873) in all genders. The optimal cut-off values of the TyG index and HOMA-IR were 7.99 and 3.39, respectively. Conclusions: The TyG index showed more effectiveness in identifying IR in Chinese T2DM patients with a BMI < 35 kg/m2 compared to HOMA-IR.

Background/Aims: Type II diabetes is a complex, chronic, and progressive disease. Glucagon-like peptide-1 (7–6) amide (GLP-1) is a gut hormone released from the L cells which stimulates insulin secretion, and promotes insulin gene expression and β-cell growth and differentiation. Elevated levels of hormone secreted by L cells are an important reason for diabetes improvement. GLP-1 secretion has been reported to be regulated by farnesoid X receptor (FXR), a transcriptional sensor for bile acids which also acts on glucose metabolism. Herein, we attempted to evaluate the effect of FXR on GLP-1 secretion in mouse enteroendocrine L cell lines, STC-1 and GLUTag, and to investigate the underlying mechanism. Methods: ELISA and Western blot assays were employed to examine the levels of GLP-1 and FXR, and the effect of FXR on GLP-1 secretion; online database, including BioGRID and KEGG were used to identify the potential interactions between FXR and proteins and involved pathways; GST pull-down and Co-Immunoprecipitation (Co-IP) assays were performed to validate FXR-CREB interaction; Luciferase reporter gene assays were used for CREB transcriptional activity determination. Results: FXR inversely regulated GLP-1 secretion in the mouse enteroendocrine L cell lines, GLUTag and STC-1. A total of 24 nonredundant human proteins were shown to be related to FXR by BioGRID; KEGG pathway analysis showed that FXR was related to glucagon signaling pathway, particularly with the transcriptional activators CREB, PGC1α, Sirt1 and CBP. CREB could positively regulate GLP-1 secretion in GLUTag and STC-1 cells. FXR combined with CREB to inhibit its transcriptional activity, thus inhibiting proprotein convertase subtilisin/ kexin type 1 (PCSK1) protein level and GLP-1 secretion. Conclusion: In the present study, we demonstrated a negative regulation of GLP-1 secretion by FXR in L cell lines, GLUTag and STC-1; FXR exerts its function in L cells through interacting with CREB, a crucial transcriptional regulator of cAMP-CREB signaling pathway, to inhibit its transcriptional activity. Targeting FXR to rescue GLP-1 secretion may be a promising strategy for type II diabetes.