Repair effect of ephedrine on lipopolysaccharide-induced microglia function injury and its mechanism / 中国药房

OBJECTIVE To study the repair effect of ephedrine on lipopolysaccharide （LPS）-induced microglia function injury and its mechanism. METHODS Human microglia cells （HMC3） were used as research objects to investigate the effects of different concentrations of ephedrine （75， 150， 300， 600 μg/mL） on the viability and apoptosis of HMC3 cells. HMC3 cells were divided into control group （without drug intervention）， LPS group （1 μg/mL）， ephedrine group （1 μg/mL LPS+300 μg/mL ephedrine）， BAY11-7082 group [1 μg/mL LPS+5 μmol/L nuclear factor-κB （NF-κB） pathway inhibitor BAY11-7082]， inhibitor group （1 μg/mL LPS+300 μg/mL ephedrine+5 μmol/L BAY11-7082） and activator group （1 μg/mL LPS+300 μg/mL ephedrine+1 μmol/L NF-κB pathway activator Prostratin）. After 24 hours of drug treatment， cell migration， the levels of soluble interleukin-6（sIL-6）， interleukin-10（IL-10）， superoxide dismutase（SOD）and malondialdehyde（MDA）， and the expressions of NF-κB pathway-related proteins were all detected. RESULTS The viability of HMC3 cells could be increased significantly by 300 μg/mL ephedrine， while the apoptotic rate was decreased significantly （P＜0.05）. Compared with the control group， the number of migrating cells was increased significantly in the LPS group； the levels of sIL-6 and MDA， the phosphorylation of NF-κB protein were increased significantly， while the levels of IL-10 and SOD were decreased significantly （P＜0.05）. Compared with the LPS group， the above indexes were reversed significantly in the ephedrine group and BAY11-7082 group （P＜0.05）. Compared with the ephedrine group， the number of migrating cells was decreased significantly in the inhibitor group； the levels of sIL-6 and MDA， the phosphorylation of NF-κB protein were decreased significantly， while the levels of IL-10 and SOD were increased significantly （P＜0.05）. The above indexes were reversed significantly in the activator group （P＜0.05）can repair cell injury by inhibiting LPS induced apoptosis， migration， inflammation and oxidant stress of HMC3 cells， the mechanism of which may be associated with inhibiting the activity of the NF-κB signaling pathway.

Relationship between hsa_circ_401724 expression and inflammatory response and pancreatic islet cell function in type 2 diabetic patients / 国际检验医学杂志

Objective To analyze the relationship between the expression of hsa_circ_401724 and the in-flammatory response in type 2 diabetes mellitus(T2DM)patients and pancreatic islet cell function.Methods A total of 102 patients with T2DM treated in Linfen Central Hospital from April 2017 to December 2022 were selected as the observation group,and 100 healthy subjects with normal glucose tolerance were se-lected as the control group during the same period.The levels of tumor necrosis factor α(TNF-α),interleukin-6(IL-6)and intercellular adhesion molecule-1(ICAM-1)in the blood of the subjects were detected by en-zyme-linked immunosorbent assay to evaluate the levels of inflammatory factors in the subjects.The relative expression level of hsa_circ_401724/U6 was calculated according to the dissolution curve,and the pancreatic islet cell function of the subjects was assessed,including homeostasis model assessment of insulin resistance(HOMA-IR)and homeostatic model assessment beta cell function(HOMA-β)as assessed by homeostasis model.Pearson correlation was used to analyze the correlation between hsa_circ_401724 expression level and inflammation and pancreatic islet cell function,and Logistics regression model was used to analyze the rela-tionship between hsa_circ_401724 expression level and inflammation and pancreatic islet cell function.Results The levels of HOMA-IR,TNF-α,IL-6 and ICAM-1 in observation group were significantly higher than those in control group,while the levels of HOMA-β in observation group were significantly lower than those in control group,with statistical significance(P＜0.05).The relative expression level of hsa_circ_401724 in observation group(0.75±0.13)was significantly higher than that in control group(0.24±0.06),and the difference was statistically significant(P＜0.05).The levels of HOMA-IR,TNF-α,IL-6 and ICAM-1 in hsa_circ_401724 high expression group were significantly higher than those in hsa_circ_401724 low expres-sion group,and the levels of HOMA-β were significantly lower than those in hsa_circ_401724 low expression group.The difference was statistically significant(P＜0.05).The relative expression level of hsa_circ_401724 was positively correlated with the levels of HOMA-IR,TNF-α,IL-6 and ICAM-1(r=0.657,0.671,0.703,0.698,P＜0.05).hsa_circ_401724 expression level was negatively correlated with HOMA-β level(r=-0.611,P＜0.05).The high expression of hsa_circ_401724 was an independent risk factor affecting the levels of HOMA-IR,HOMA-β,TNF-α,IL-6 and ICAM-1 in T2DM patients(P＜0.05).Conclusion The high ex-pression of hsa_circ_401724 is related to the inflammatory response and the decline of pancreatic islet cell function in T2DM patients.

Dapagliflozin attenuates endothelial cell pyroptosis and dysfunction induced by oxidized low-density lipoprotein / 中国组织工程研究

BACKGROUND:Dapagliflozin,an inhibitor of sodium-glucose cotransporter 2,can delay the progression of atherosclerosis by regulating glucose metabolism,inhibiting inflammation and improving endothelial cell function. OBJECTIVE:To study the effect of dapagliflozin on cell pyroptosis and endothelial dysfunction induced by oxidized low-density lipoprotein. METHODS:Human umbilical vein endothelial cells were divided into a control group(no intervention),a model group(treated with oxidized low-density lipoprotein for 24 hours),and a dapagliflozin group(treated with oxidized low-density lipoprotein + dapagliflozin for 24 hours).Endothelial cell proliferation activity was measured by cell counting kit-8 assay.The levels of intercellular adhesion molecule 1,vascular cell adhesion molecule 1,and monocyte chemotactic protein-1 in cell supernatant were detected using ELISA.Nitric oxide level in the cells was detected by nitrate reductase assay.The pyroptosis rate and characteristics of endothelial cells were detected by Hoechst 33342/PI fluorescence co-staining and lactate dehydrogenase release assay.The protein expression levels of NLRP3,caspase-1,GSDMD,interleukin-1β,and interleukin-18 were detected by western blot assay. RESULTS AND CONCLUSION:(1)Oxidized low-density lipoprotein could cause pyroptosis and dysfunction of endothelial cells.(2)Compared with the control group,the level of nitric oxide and cell activity were decreased(P<0.05),while lactate dehydrogenase,intercellular adhesion molecule 1,vascular cell adhesion molecule 1,and monocyte chemotactic protein-1 levels were significantly increased in the model group(P<0.05).Compared with the model group,cell activity and nitric oxide levels significantly increased(P<0.05),but lactate dehydrogenase,intercellular adhesion molecule 1,vascular cell adhesion molecule 1,and monocyte chemotactic protein-1 levels were significantly diminished in the dapagliflozin group(P<0.05).(3)Compared with the model group,cell pyroptosis rate and the protein expression of pyroptosis factor NLRP3,caspase-1,GSDMD,interleukin-18 and interleukin-1β significantly reduced in the dapagliflozin group(P<0.05).(4)The results indicate that dapagliflozin inhibits oxidized low-density lipoprotein-induced endothelial pyroptosis and ameliorates endothelial cell dysfunction.

Effect of Gualou Xiebai Banxiatang on Myocardial Microangiogenesis and HIF-1α/VEGF-related Pathways in Myocardial Ischemia Model Rats / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Gualou Xiebai Banxiatang on cardiac function and myocardial histopathological changes in rats with ischemic myocardial injury， and to observe the effect of myocardial microvascular density （MVD）， phosphatidylinositol 3-kinase （PI3K）， mammalian target of rapamycin （mTOR）， hypoxia-inducible factor-1 alpha （HIF-1α）， and vascular endothelial growth factor （VEGF） signaling pathways on myocardial microangiogenesis. MethodSeventy male SD rats were randomly selected， with six rats in the normal group. The remaining rats were fed a high-fat diet and injected with isoproterenol hydrochloride （ISO，80 mg·kg-1·d-1， 2 d） to induce a hyperlipidemia-based ischemic heart disease model. After successful modeling， the rats were randomly divided into the model group， high， medium， and low dose groups of Gualou Xiebai Banxiatang， and the metoprolol group. The high， medium， and low dose groups of Gualou Xiebai Banxiatang were given Gualou Xiebai Banxiatang at 10.42， 5.21， 2.61 g·kg-1·d-1， respectively， while the metoprolol group was given metoprolol at 2.6 mg·kg-1·d-1. Both the normal and model groups were given an equivalent volume of physiological saline for 28 days. After the intervention， relevant tests were conducted， and serum was collected to measure heart function-related indicators. Hematoxylin-eosin （HE） and Masson staining were performed on ventricular tissue to observe pathological changes under a light microscope. Immunohistochemistry （IHC） was used to detect the positive expression of platelet endothelial cell adhesion molecule （CD31）. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression of N-terminal pro-brain natriuretic peptide （NT-proBNP） and VEGF. Western blot was used to detect the protein expression levels of PI3K/mTOR/HIF-1α/VEGF. ResultCompared with the normal group， the model group showed significantly increased serum levels of LDH， CK， CK-MB， NT-proBNP， and VEGF （P<0.01）， significantly increased collagen volume fraction （CVF） （P<0.01）， significantly decreased MVD （P<0.01）， and elevated protein expression levels of PI3K， mTOR， HIF-1α， and VEGF （P<0.05， P<0.01）. Compared with the model group， the metoprolol group had significantly lower serum levels of LDH， CK， CK-MB， and NT-proBNP （P<0.01）， significantly higher VEGF levels （P<0.01）， significantly decreased CVF （P<0.01）， significantly increased MVD （P<0.01）， and significantly increased protein expression levels of PI3K， mTOR， and VEGF （P<0.01）， with no statistically significant change in HIF-1α protein expression. Compared with the model group， the high and medium dose groups of Gualou Xiebai Banxiatang had decreased serum levels of LDH， CK， CK-MB， and NT-proBNP （P<0.05， P<0.01）， increased VEGF levels （P<0.05， P<0.01）， significantly reduced CVF （P<0.01）， increased MVD （P<0.05， P<0.01）， and significantly increased protein levels of PI3K， mTOR， HIF-1α， and VEGF （P<0.01）. In the low dose group of Gualou Xiebai Banxiatang， compared with the model group， serum levels of LDH and NT-proBNP were decreased （P<0.05）， VEGF was increased （P<0.05）. Moreover， CVF was decreased （P<0.05）， and the protein expression levels of PI3K， mTOR， HIF-1α， and VEGF were significantly increased （P<0.01）. ConclusionGualou Xiebai Banxiatang can improve cardiac function， reduce myocardial pathological damage， enhance endothelial cell function， promote myocardial microvascular formation， and upregulate the expression of PI3K， mTOR， HIF-1α， and VEGF proteins in myocardial tissue in rats with ischemic myocardial injury.

Effect and Potential Mechanism of Inhibition of Long Non-coding RNA MALAT1 on Glycolipipotoxicity-induced Endothelial Cell Dysfunction / 中国循环杂志

Objectives:To investigate the effect of inhibition of long non-coding RNA(lnc RNA)in human metastasis associated lung adenocarcinoma transcript 1(MALAT1)on glycolipitoxicity-induced human umbilical vein endothelial cell dysfunction. Methods:Human umbilical vein endothelial cells were treated with glucose and palmitic acid in vitro to establish the glycolipitoxic endothelial cell models.Following groups were examined:control group,high-glucose and high-fat group,high-glucose and high-fat + non-targeting RAN control group,high-glucose and high-lipid+MALAT1 siRNA group,and high-glucose and high-lipid+MAPK1 siRNA group.RT-qPCR was used to detect the mRNA expression of MALAT1 and MAPK1.Western blot was used to detect the expression levels of autophagy,mitochondrial fusion division,apoptosis,and pathway-related proteins.Immunofluorescence confocal localization was used to detect the fluorescence colocalization of autophagy and lysosome-related proteins.The number of autophagolysosomes in endothelial cells was observed by transmission electron microscopy.Mitochondrial probe staining was used to detect mitochondrial morphology,immunofluorescence was used to detect intracellular reactive oxygen species(ROS)production,flow cytometry was used to detect the apoptosis of cells in each group,cell proliferation and scratch assays were used to detect the proliferation and migration ability of cells in different groups at different time points.The angiogenesis was quantified by counting the number of new blood vessels in each group. Results:Compared with the control group,the expression of lncRNA MALAT1 mRNA and the expression of phosphorylated mito-activated protein kinase 1(p-MAPK1)were upregulated(both P＜0.05)and the expression of phosphorylated mammalian target protein(p-mTOR)was downregulated in the high-glucose and high-fat group and the high-sugar and high-fat control group(all P＜0.01).Compared with the high-glucose and high-fat non-targeting RNA control group,the expressions of microtubule-associated protein 1A/1B-light chain 3(LC3)and p62 were downregulated(P＜0.01,P＜0.05),LC3 and lysosome-associated membrane protein 2(LAMP2)protein co-localized positive fluorescence particles were increased(both P＜0.01),number of lysosomes were decreased,the expression of ROS was decreased(P＜0.01),the expression level of mitochondrial fusion protein optic nerve atrophin 1(OPA1)was increased(P＜0.05),the expressions of cleaved caspase-3 and BCL-2-related X protein(BAX)were decreased and BCL-2 was increased(all P＜0.05),cell proliferation,migration,and tube-forming ability were increased(all P＜0.01),and the expression of p-MAPK1 was decreased(P＜0.05)and p-mTOR expression was increased(both P＜0.05)in the high-glucose and high-lipid+si-MALAT1 group.Compared with the high-glucose and high-fat non-targeting RNA control group,the expression of p-MAPK1 in endothelial cells was decreased and the expression of p-mTOR was increased in the high-glucose and high-lipid+si-MAPK1 group(both P＜0.01). Conclusions:Inhibition of lncRNA MALAT1 expression can reduce the level of mitophagy in glycolipidotoxic environments,reduce apoptosis of endothelial cells and improve endothelial cell function,which may be related to the regulation of MAPK1/mTOR signaling pathway.

Correlation between islet α cell function and peripheral neuropathy in patients with type 2 diabetes mellitus

Abstract Background: This study explored the correlation between pancreatic islet α cell function, as reflected by the plasma glucagon levels, and Diabetic Peripheral Neuropathy (DPN) in patients with Type 2 Diabetes Mellitus (T2DM). Methods: A total of 358 patients with T2DM were retrospectively enrolled in this study and divided into the Non-DPN (NDPN) group (n = 220) and the DPN group (n = 138). All patients underwent an oral glucose tolerance test to detect levels of blood glucose, insulin and glucagon, and the Area Under the Curve (AUC) for Glucagon (AUCglu) was used to estimate the overall glucagon level. The Peripheral Nerve Conduction Velocity (PNCV), Amplitude (PNCA) and Latency (PNCL) were obtained with electromyography, and their Z scores were calculated. Results: There were significant differences regarding the age, disease duration, serum levels of alanine aminotransferase, aspartate aminotransferase, urea nitrogen, high-density lipoprotein, and 2h-C peptide between these two groups (p < 0.05). The NDPN group had higher glucagon levels at 30, 60 and 120 min and AUCglu (p < 0.05). The Z-scores of PNCV and PNCA showed an increasing trend (p < 0.05), while the Z-score of PNCL showed a decreasing trend (p < 0.05). The glucagon levels were positively correlated with PNCV and PNCA, but negatively correlated with PNCL, with Gluca30min having the strongest correlation (p < 0.05). Gluca30min was independently related to PNCV, PNCL, PNCA and DPN, respectively (p < 0.05). The function of pancreatic α islet cells, as reflected by the plasma glucagon level, is closely related to the occurrence of DPN in T2DM patients. Conclusion: Gluca30min may be a potentially valuable independent predictor for the occurrence of DPN.

Association between elevated serum uric acid levels and islet beta cell function indices in newly diagnosed type 2 diabetes mellitus-a one year cross sectional study at tertiary care center

Background: Serum uric acid (SUA) has been reported as a risk factor for type 2 diabetes mellitus (T2DM). Even though various studies concluded that SUA plays an essential role in DM onset, association between SUA and pancreatic islet ? cell function and the effect of gender and body mass index (BMI) on it in is still unclear. Methods: A hospital based one-year cross-sectional study was conducted and required data was collected from 76 patient who were newly diagnosed T2DM. All patients were investigated for SUA, and homeostasis model assessment-insulin resistance (HOMA-IR) was calculated using the HOMA2 calculator. Results: Mean SUA level among the males was 4.65±1.81 mg/dl and among the females was 4.31±1.94 mg/dl. ? pancreatic cell function index was estimated using HOMA-IR. Mean HOMA-IR level among the male study population was 5.01±7.44 and 5.02±4.63 among the females. A positive and significant correlation was observed between SUA and HOMA-IR (r=0.2283, p=0.0489) at 5% level, and was more pronounced among the female population (r=0.5127, p=0.0175). Correlation between HOMA-IR and BMI was found to be positive and significant (r=0.4948, p=0.0001). On plotting multiple regression analysis, coefficient of determination (R²) was 0.8374 (p<0.05), indicating significant contribution of all variables when combined towards HOMA-IR. Conclusions: Present study demonstrates that SUA harbours a positive and significant correlation with pancreatic islet ? cell function index among newly diagnosed T2DM patients and is influenced by gender and BMI.

A cross-sectional study to assess beta-cell function in individuals with recently diagnosed young-onset type 2 diabetes mellitus and its’ complications / Journal of the ASEAN Federation of Endocrine Societies

Objective@#The primary objective was to assess beta-cell function of recently-diagnosed young-onset type 2 diabetes mellitus (T2DM) individuals using basal and stimulated C-peptide levels. The secondary objective was to examine the association between C-peptide with metabolic factors and diabetes complications.@*Methodology@#A cross-sectional study was conducted for young-onset T2DM individuals aged 18-35 years with a disease duration of not more than 5 years. Plasma C-peptide was measured before and after intravenous glucagon injection. Demographic data, medical history and complications were obtained from medical records and clinical assessment. Continuous data were expressed as median and interquartile range (IQR). Categorical variables were described as frequency or percentage. Multivariable linear regression analysis was used to determine factors associated with C-peptide levels.@*Results@#113 participants with young-onset T2DM with a median (IQR) age of 29.0 (9.5) years and 24 (36) months were included in this study. The median (IQR) basal and stimulated C-peptide was 619 (655) pmol/L and 1231 (1024) pmol/L. Adequate beta-cell function was present in 78-86% of the participants based on the basal and stimulated C-peptide levels. We found hypertension, obesity and diabetic kidney disease (DKD) to be independently associated with higher C–peptide levels. In contrast, females, smokers, those on insulin therapy and with longer duration of disease had lower C–peptide levels.@*Conclusion@#Most recently diagnosed young-onset T2DM have adequate beta-cell function. Elevated C-peptide levels associated with obesity, hypertension and diabetic kidney disease suggest insulin resistance as the key driving factor for complications.

Expression of POU2F2 in clear cell renal cell carcinoma and its effects on the biological behavior of the cancer cells / 现代泌尿外科杂志

【Objective】 To investigate the expression of transcription factor POU domain class 2 transcription factor 2 (POU2F2) in clear cell renal cell carcinoma (ccRCC) and human renal cancer cell lines (786-O and ACHN) and its effects on the cells’ biological behaviors such as proliferation, migration and invasion in vitro. 【Methods】 The mRNA expressions of POU2F2 in ccRCC tissues, adjacent normal tissues, cell lines 786-O and ACHN were detected with real-time polymerase chain reaction (qRT-PCR). The protein expression of POU2F2 in ccRCC tissues and adjacent normal tissues were detected with immunohistochemistry. The effects of knockdown of POU2F2 on the mRNA and protein expressions of epithelial mesenchymal transformation (EMT)-related tumor markers were detected with qRT-PCR and Western blot. 【Results】 The mRNA expression of POU2F2 in ccRCC tissues was significantly higher than that in adjacent normal tissues, and was correlated with patients’ gender, WHO/ISUP nuclear grade and TNM stage. The protein expression of POU2F2 was significantly higher in ccRCC tissues than in adjacent normal tissues, and was correlated with tumor pathological grade and TNM stage. The mRNA expression of POU2F2 was significantly decreased in 786-O cells after sh-POU2F2-1013 plasmid transfection (P<0.05); the proliferation ability, clonal formation rate, migration ability and invasion ability were significantly reduced (P<0.05). Knockdown of POU2F2 down-regulated the mRNA and protein expressions of MMP2, MMP9 and Twist in 786-O cells, while up-regulated E-ca expression. 【Conclusion】 The mRNA expression of POU2F2 was significantly up-regulated in ccRCC tissues and renal cancer cells. Knockdown of POU2F2 inhibited the proliferation, migration and invasion of cells in vitro, and slowed or inhibited the occurrence and development of renal cancer.

Immunophenotype and function of peripheral blood lymphocyte subsets in Chinese rhesus macaques / 中华微生物学和免疫学杂志

Objective:To provide data reference for using Chinese rhesus macaques as research model by studying the immunophenotype and function of peripheral blood lymphocytes in Chinese rhesus macaques.Methods:By optimizing antibody clones and fluorescent colors, the lymphocyte subset assay and T cell function assay panels were determined. Then the panels were used to analyze the proportion of T, B, NK and other cell subsets in peripheral blood mononuclear cells (PBMCs) in 15 healthy Chinese rhesus monkeys, and the ability of T cells to secrete cytokines after non-specific stimulation.Results:Two multi-color flow cytometry analytic panels were established. Panel 1 could simultaneously detect a variety of lymphocyte subsets, including cytotoxic T lymphocytes, follicular helper T cells, regulatory T cells, B cells and NK cells. Panel 2 could detect the functions of multiple T cell subsets and the expression of immune checkpoint moleculars. The mean percentages of T, B, NK, Tfh, Treg, CD16 + NK and CD56 + NK cells in PBMCs of the Chinese rhesus macaques were (75.32±7.73)%, (13.22±7.50)%, (0.88±0.48)%, (0.73±0.27)%, (0.75±0.43)%, (47.87±22.35)% and (10.69±12.41)%. After non-specific stimulation, the proportion of CD4 + T cells secreting IL-2 and TNF-α was higher than that of CD8 + T cells, and the proportion of CD8 + T cells secreting CD107a and IFN-γ was higher than that of CD4 + T cells, while the proportion of CD4 + and CD8 + T cells secreting IL-17A was low. Conclusions:This study established a multi-color flow detection scheme that could simultaneously detect multiple cellular surface molecules and cytokines at the single cell level and could accurately and comprehensively analyze the immune cell subsets, functions and the immune checkpoint molecules in peripheral blood of Chinese rhesus macaques, providing a new experimental method and basic data for the development of vaccines and drugs against infectious diseases.

Recent advance in telocytes of fetal and newborn organs and tissues / 国际儿科学杂志

Telocyte(TC)is a novel type of interstitial cell, which has been identified in various organs and tissues of both humans and animals.Recent studies have confirmed that TC plays crucial roles in regulating tissue and organ development, maintaining tissue homeostasis, participating in tissue repair and regeneration, and modulating the immune response.This article provides a comprehensive review of the current research progress on the distribution, immunophenotype, and cellular functions of TC in the respiratory, circulatory, digestive, urinary, reproductive, locomotor systems, and other organs and tissues during fetal and neonatal development.This review aims to serve as a valuable reference for future investigations into the structure and functions of TC.

The effect of varied exercise intensity on antioxidant function, aortic endothelial function, and serum lipids in rats with non-alcoholic fatty liver disease / El efecto del ejercicio de intensidad variada sobre la función antioxidante, la función endotelial aórtica y los lípidos séricos en ratas con enfermedad del hígado graso no alcohólico

Abstract This study aimed to compare the effects of diet and exercise of different intensities on antioxidant function, aortic endothelial cell function and serum lipids in NAFLD (nonalcoholic fatty liver disease) rats. Fifty Sprague-Dawley (SD) rats (180-220g) were randomly divided into two experimental groups and fed either a standard rodent chow diet (CON; n=10) or a high-fat diet (HFD; n=40). After 16 weeks, the animals that received the HFD were randomly separated into a high-fat control group (HFC; n=10) or three exercise training groups: HFD and low-intensity exercise (LE; n=10), HFD and moderate-intensity exercise (ME; n=10), and HFD and incremental intensity exercise (IE; n=10). These experimental rats keep sedentary or trained for the next six weeks. A detection kit was used to detect nitric oxide synthase (NOs), nitric oxide (NO), malondialdehyde (MDA) and other markers of aortic oxidative stress. The expression levels of endothelial nitric oxide synthase (e-NOS) and endothelin-1 (ET-1) were detected by immunohistochemistry. TC, TG, and other lipid metabolism parameters were detected by an automatic analyzer. Exercise with different intensities could improve lipid metabolism, enhance antioxidant function, reduce MDA (P<0.01), increase NO (P<0.01), and improve the expression of e-NOS and ET-1 (P<0.01) protein levels in NAFLD rats. Decreased blood lipids were exhibited in all exercise groups. Notably, the moderate-intensity exercise demonstrated more effect on increasing glutathione (GSH) contents (P<0.01) and decreased the expression of ET-1 protein levels (P<0.01). The results showed that exercise at different intensities improved lipid metabolism and enhanced anti-oxidation function. Moderate exercise could improve the function of aortic endothelial cells.

Resumen Este estudio tuvo como objetivo comparar los efectos de la dieta y el ejercicio a diferentes intensidades sobre la función antioxidante, la función de las células endoteliales aórticas y los lípidos séricos en ratas NAFLD (con enfermedad del hígado graso no alcohólico) y alimentados con una dieta estándar para roedores (CON; n = 10) o con una dieta alta en grasas (HFD; n = 40). Después de 16 semanas, los animales que recibieron HFD se separaron aleatoriamente en un grupo de control alto en grasas (HFC; n=10) o tres grupos de entrenamiento físico: HFD y ejercicio de baja intensidad (LE; n=10), HFD y ejercicio de intensidad moderada (ME; n=10), y HFD y ejercicio de intensidad incremental (IE; n=10). Estas ratas experimentales se mantuvieron sedentarias o entrenadas durante las próximas seis semanas. Se utilizó un kit de detección para determinar óxido nítrico sintetasa (NO), óxido nítrico (NO), malondialdehído (MDA) y otros marcadores de estrés oxidativo aórtico. Los niveles de expresión de la óxido nítrico sintetasa endotelial (e-NOS) y endotelina-1 (ET-1) se detectaron mediante inmunohistoquímica. El analizador automático detectó TC, TG y otros parámetros del metabolismo de los lípidos. El ejercicio con diferente intensidad mejoró el metabolismo de los lípidos, mejoró la función antioxidante, redujo la MDA (P <0,01), aumentó el NO (P <0,01) y mejoró la expresión de los niveles de proteína e-NOS y ET-1 (P <0,01) en ratas NAFLD. Se observó una disminución de los lípidos en sangre en todos los grupos de ejercicio. En particular, el ejercicio de intensidad moderada demostró un mayor efecto en el aumento del contenido de glutatión (GSH) (P<0,01) y disminuyó la expresión de los niveles de proteína ET-1 (P<0,01). Los resultados mostraron que el ejercicio a diferentes intensidades mejoró el metabolismo de los lípidos y mejoró función antioxidante. El ejercicio moderado podría mejorar la función de las células endoteliales aórticas.

Effect of annexin A1 on the proliferation, migration and invasion of papillary thyroid carcinoma / 中华内分泌外科杂志

Objective:To investigate the effect of ANXA on biological behavior of papillary thyroid carcinoma (PTC) cells by interfering with the expression of annexin A1 (ANXA1) in PTC cell lines by short hairpin RNA (shRNA) .Methods:The shRNA with specific and high efficiency was designed to specifically interfere with the expression of ANXA1 in TPC-1 and BCPAP cell lines, and transfect the TPC-1 and BCPAP cell lines respectively, including specific ANXA1 interference and negative control virus transfection, and they were divided into shANXA1 group and negative control virus group. Semi-quantitative reverse transcription PCR (Q-PCR) and Western Blot were employed to verify gene expression. The shANXA1 group was used as the experimental group, the untransfected virus group and the negative control virus group were set as the control groups. The expression levels of ANXA1 in the three groups were compared and the shRNA interference efficiency was verified. The effects of ANXA1 knockdown on the proliferation, migration and invasion of TPC-1 and BCPAP cell lines were investigated by scratch, CCK8 and Transwell invasion experiments. Independent sample t test was used to compare the means between the two groups, and one-way analysis of variance was employed to compare multiple groups, with P<0.05 as statistically significant. Results:shRNA could efficiently silence the expression of ANXA1 at the transcription and translation level in PTC cell lines. Compared with the negative control cells, the cells proliferated after successful lentiviral transfection of TPC-1 and BCPAP (BCPAP, 24h: F= 25.15, P<0.001; 48h: F=6.44, P<0.001; 48h: F=46.94, P<0.001; TPC-1, 24h: F=207.50, P<0.001; 48h: F=202.45, P<0.001; 48h: F=55.89, P<0.001) , its migration (BCPAP, F=12511.10, P<0.001; TPC-1, F=3966.10, P<0.001) and invasion ability (BC-PAP: F=94.65, P<0.001; TPC-1: F=681.74, P<0.001) significantly decreased. Conclusion:After shRNA knock-down of ANXA1 gene, the proliferation, migration and invasion ability of TPC-1 and BCPAP cell lines decreased significantly, indicating that silencing this gene can reduce tumor aggressiveness, and initially reveals that ANXA1 may be an important potential in PTC biotherapy Target.

Relationship between the circular RNA_0005414 expression level and the islet cell function in patients with type 2 diabetes mellitus / 中华内分泌代谢杂志

Objective:To investigate the relationship between the expression level of circular RNA_0005414 and islet cell function in type 2 diabetes patients.Methods:A total of 110 patients with type 2 diabetes and 106 cases of normal glucose tolerance (control group) in Uygur populations, 64 cases of type 2 diabetes mellitus and 63 cases of normal glucose tolerance (control group) in Han populations were enrolled in the study. All subjects underwent oral glucose tolerance test chemistry panel. Homeostasis model assessment for insulin resistance (HOMA-IR) and β cell function (HOMA-β) were evaluated by homeostasis model as islet cell function indexes. The differentially expressed circular RNAs were screened using RNA sequencing from the peripheral blood monocytes of 5 Uygur patients with type 2 diabetes mellitus and matched controls. The expression level of a significantly up-regulated circular RNA_0005414 was detected and verified, and the relationship between the expression level of circular RNA_0005414 and islet cell function was analyzed.Results:Differential expression profiles of circular RNAs were found in Uygur type 2 diabetic patients . The expression level of circular RNA_0005414 in Uygur type 2 diabetic group was higher than that in Uygur control group ( P<0.01), the expression level of circular RNA_0005414 in Han type 2 diabetic group was higher than that in Han control group ( P<0.01), the expression level of circular RNA_0005414 in Uygur type 2 diabetes group was higher than that in Han type 2 diabetes group, but the difference was not statistically significant ( P>0.05). In the Uyghur and Han groups, Spearman correlation analysis showed that the expression level of circular RNA_0005414 was positively correlated with fasting blood glucose, 2 h plasma glucose after glucose loading, HbA 1C, total cholesterol, fasting insulin, HOMA-IR ( P<0.05) and negatively correlated with HOMA-β ( P<0.01). Partial correlation analysis showed that circular RNA_0005414 expression level was positively correlated with fasting blood glucose, HbA 1C, and HOMA-IR ( P<0.01). Multivariate linear regression analysis showed that circular RNA_0005414 was the only factor affecting HOMA-β in Uygur patients with type 2 diabetes. Conclusion:The expression level of circular RNA_0005414 was closely related to islet cell function in Uygur type 2 diabetes patients, the up-regulation of circular RNA_0005414 may be involved in the occurrence and development of type 2 diabetes in Uygur.

Protective Effect of Tongluo Shenggu Capsule on Function Damage of Human Umbilical Vein Endothelial Cells Induced by Glucocorticoid / 中国实验方剂学杂志

Objective:To observe the effect of Tongluo Shenggu capsule （TLSGC） on glucocorticoid-induced vascular endothelial cell functional damage， and to preliminally explore the mechanism of action through MEK-ERK signaling pathway. Method:The blood vessel of aorta rings of normal SD rats were induced <italic>in vitro</italic> intervention with methylprednisolone sodium succinate （MPS， 0.04 g·L^-1） and/or vascular endothelial growth factor （VEGF， 20 μg·L^-1）， and were treated with TLSGC（12.5， 25， 50 μg·L^-1） continuously for 5 days to observe the number， length and area of microvascular ring buds．In addition， human umbilical vein endothelial cells （HUVEC） induced by VEGF（20 μg·L^-1） were added into MPS（0.04 g·L^-1） and TLSGC （12.5， 25， 50 μg·L^-1） were added. Then， Transwell migration， Transwell invasion and lumen formation experiments were used to detect the migration， invasion and lumen formation ability of HUVEC， respectively. The content of nitric oxide（NO） in the cell supernatant was detected by nitrate reductase method， the content of endothelin 1（ET-1） in the cell supernatant was detected by dry powder method. Moreover， the protein contents of vascular endothelial growth factor receptor 2 （VEGFR2）， extracellular signal-regulated kinase （ERK）， phospho-extracellular signal-regulated kinase （p-ERK）， mitogen extracellular kinase1（MEK） and phosphorylated mitogen extracellular kinase1（p-MEK） in the cells were determined by Western blot. Result:Compared with the normal group， MPS could significantly inhibit the number， length and area of VEGF-induced rat thoracic aortic ring microvessels， HUVEC cell migration， invasion and lumen formation ability. It could reduce NO content and increase ET-1 content. MPS could also significantly reduce the protein content of VEGF-induced VEGFR2， p-MEK and p-ERK in HUVEC（<italic>P</italic><0.05，<italic>P</italic><0.01）. Compared with the model group， TLSGC could dose-dependently increase the number， length and area of MPS-induced abnormally reduced rat thoracic aortic ring microvessels， promote MPS-induced abnormally decreased HUVEC cell migration， invasion and lumen formation ability. It could increase the protein contents of NO， VEGFR2， p-MEK and p-ERK in HUVEC， and reduce abnormally increased ET-1 content（<italic>P</italic><0.05<italic>，P</italic><0.01）. Conclusion:TLSGC has a protective effect on the damage of angiogenesis and secretion of vascular endothelial cells induced by glucocorticoid， and the mechanism may be related to the activation of MEK/ERK signaling pathway.

Progress on Hypoglycemic Effect and Mechanism of Momordica charantia / 中国实验方剂学杂志

Momordica charantia has been a traditional Chinese medicine （TCM） and food since ancient times. The discussions on its nature， taste and efficacy in ancient books of TCM are almost the same. With a high nutritional value， M. charantia is rich in a variety of vitamins and minerals， and has been widely used in the production of a wide range of dietary supplements and functional foods. At the same time， M. charantia is one of the most deeply studied natural medicines in traditional alternative medicine， with a wide range of pharmacological effects， especially in the treatment of metabolic diseases. Clinical trials have confirmed that M. charantia has a hypoglycemic effect， and could reduce blood lipids and weight loss， so as to improve metabolism in a comprehensive manner. According to the study on the mechanism of M. charantia in the treatment of diabetes， M. charantia could reduce blood sugar by improving islet β-cell function， improving insulin resistance， inhibiting intestinal glucose absorption and resisting inflammation and oxidative stress. However， at present， there is a lack of unified standards for the hypoglycemic effects and various mechanisms of action of M. charantia， and the safety has not been fully confirmed. Further studies shall be conducted to investigate the hypoglycemic effect and mechanisms of M. charantia， explore active components of M. charantia， define the pharmacodynamics material basis， extract monomer compounds with a clear structure and confirm its effectiveness and safety， which is helpful to develop and utilize the homologous value of medicine and food of M. charantia and further apply it in clinic. The application of the hypoglycemic effect of M. charantia in clinic has important economic benefits and a social significance.

Clinical study on treatment of senile hypertension with Bushen-Yijing-Tiansui Decoction combined with levoclodipine besylate tablets / 国际中医中药杂志

Objective:To observe the therapeutic effect of Bushen-Yijing-Tiansui Decoction combined with levoclodipine besylate in the treatment of senile hypertension. Methods:A total of 150 elderly hypertensive patients admitted in our hospital from January 2019 to February 2020 were randomly divided into 2 groups by a random number table method, with 75 in each. Both groups were given basic symptomatic treatment of other comorbidities and concurrent health education. The control group received oral amlodipine besylate tablets, and the observation group received Bushen-Yijing-Tiansui Decoction on the basis of the control group. Both groups were treated for 4 weeks. The TCM syndromes were scored before and after treatment, manometer was used to measure blood pressure and heart rate, the serum ET-1 level was detected by Enzyme-Linked Immunosorbent Assay (ELISA), and the nitrate reductase method was used to detect serum NO levels, and adverse events occurred during treatment in the two groups were recorded. Results:The total effective rate of the observation group was 88.0% (66/75), and the control group was 73.3% (55/75), and the comparison difference in 2 groups was statistically significant ( χ2 =5.172, P=0.022). After treatment, the symptom scores of pain, palpitations, constipation, insomina, sore feeling on back and legs of the observation group were signigicantly lower than those in the control group ( t value were 5.814, 10.397, 12.094, 7.019, 6.121, all Ps<0.001). After treatment, heart rate [(79.60 ± 4.80) times/min vs. (84.30 ± 5.40) times/min, t=5.634], SBP [(144.8 ± 7.90) mmHg vs. (150.60 ± 7.90) mmHg, t=4.729], DBP [(78.80 ± 8.20) mmHg vs. (85.20 ± 9.10) mmHg, t=4.525] of the observation group were signigicantly lower than those of the control group ( P<0.01). After treatment, the serum ET-1 [(179.25 ± 30.45) μmol/L vs. (190.83 ± 30.89) μmol/L, t=2.312] of the observation group was signigicantly lower than that of the control group ( P<0.05), NO [(58.51 ± 8.78) μmol/L vs. (54.12 ± 9.03) μmol/L, t=3.019] of the observation group was signigicantly higher than that of the control group ( P<0.05). During treatment, the incidence of adverse events in the control group was 4.0% (3/75), and the observation group was 1.3% (1/75), and the two groups had no significant difference ( χ2 =1.027, P=0.311). Conclusion:Bushen-Yijing-Tiansui Decoction combined with levoclodipine besylate in the treatment of senile hypertension can relieve the clinical symptoms and blood pressure of patients, improve the function of vascular endothelial cells.

Study on the correlation between serum vitamin D level, parathyroid hormone and type 2 diabetes mellitus in Inner Mongolia / 中华临床营养杂志

Objective:To evaluate the correlation of serum vitamin D (VitD) and parathyroid hormone (PTH) with insulin resistance and islet β-cell function in patients with type 2 diabetes mellitus (T2DM), and to analyze the role of serum VitD and PTH in the progression of T2DM.Methods:A total of 376 T2DM patients hospitalized in endocrinology department from January 2018 to January 2021 were selected. The baseline data were collected and the biochemical indexes were determined. Patients were divided into 3 groups according to serum VitD level, including 220 cases in deficiency group [25-(OH)D ≤ 20 μg/L], 107 cases in insufficiency group [25-(OH)D>20 and ≤ 30 μg/L] and 49 cases in sufficiency group [25-(OH)D > 30 μg/L]. Meanwhile, 31 of the patients were classified into PTH decreased group (PTH < 25.16 ng/L), 137 into normal PTH group (PTH ≥ 25.16 and < 38.35 ng/L) and 208 into PTH elevated group ( PTH ≥ 38.35 ng/L). According to body mass index (BMI), patients were divided into normal weight group (18.5 kg/m 2 ≤ BMI ≤ 23.9 kg/m 2), overweight group (BMI ≥24 and ≤ 27.9 kg/m 2) and obese group (BMI ≥ 28 kg/m 2). Results:Among the three groups defined by serum VitD level, comparisons of glucose metabolism and calcium and phosphorus metabolism indicators showed no significant differences in BMI, fasting insulin (FINS), fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance index (HOMA-IR), serum calcium and phosphorus (all P > 0.05). The levels of glycated hemoglobin (HbA1c) and PTH in vitamin D deficiency group and sufficiency group were significantly lower compared with vitamin D deficiency group (both P < 0.05). Among the three groups defined by PTH level, there were no significant differences in BMI, FINS, FPG, HbAlc, HOMA-IR, and serum calcium (all P > 0.05). Serum phosphorus in the PTH elevated group was significantly lower compared with PTH decreased and normal PTH group ( P = 0.000), and VitD in the PTH elevated group was significantly lower compared with PTH decreased group ( P = 0.002). There were significant differences in age and blood phosphorus among the three groups defined by BMI level (all P<0.05). According to the analysis of clinical indexes of different nationalities, the level of VitD in Mongolians was significantly higher than that in Han nationality patients ( P <0.034). Spearman correlation analysis showed that VitD was negatively correlated with PTH and HOMA-IR and positively correlated with serum calcium. PTH was negatively correlated with serum calcium and phosphorus, and positively correlated with HOMA-IR. There was a significant negative correlation between normal PTH and VitD. Multiple linear regression analysis showed that HOMA-IR and homeostasis model assessment of β-cell function (HOMA-β) were protective factors, and FPG and FINS were risk factors for HOMA-IR and HOMA- β. Conclusion:There is a negative correlation between VitD and insulin resistance, and a positive correlation between PTH and insulin resistance, suggesting that VitD and PTH are possibly two impacting factors for T2DM pathogenesis.

Mechanism of Jinqi Jiangtang Tablets in treatment of pancreatic β cell dysfunction based on network pharmacology and molecular docking technology / 中国中药杂志

The present study investigated the therapeutic efficacy and potential mechanism of Jinqi Jiangtang Tablets(JQJT) on pancreatic β cell dysfunction based on network pharmacology and molecular docking technology. TCMSP platform was used to retrieve the chemical components and targets of the three Chinese herbal medicines of JQJT. The genes were converted to gene symbol by the UniProt, and its intersection with targets related to pancreatic β cell function in GeneCards and CTD databases was obtained. The drugs, active components and common targets were imported into Cytoscape 3.8.2 to plot the drug-component-target network. The main effective components and targets were obtained by software analysis. The drug targets and targets related to pancreatic β cell function were imported separately into the STRING platform for the construction of protein-protein interaction(PPI) networks. The two PPI networks were merged by Cytoscape 3.8.2 and the key targets were obtained by plug-in CytoNCA. The targets obtained from drug-component-target network and PPI networks were imported into DAVID for GO analysis and KEGG enrichment analysis. AutoDock was used to carry out molecular docking of main active components and core targets and Pymol was used to plot the molecular docking diagram. The results showed that there were 371 active components and 203 targets related to JQJT and 2 523 targets related to pancreatic β cell damage, covering 136 common targets. The results revealed core targets(such as PTGS2, PTGS1, NOS2, ESR1 and RXRA) and effective key components(such as quercetin, kaempferol, luteolin, β-carotene and β-sitosterol). KEGG enrichment analysis indicated that apoptosis, inflammation, and other signaling pathways were mainly involved. Molecular docking results showed that the main active components could spontaneously bind to the targets. This study preliminarily revealed the mechanism of JQJT in improving pancreatic β cell damage through multi-component, multi-target and multi-pathway, and provided a theoretical basis for JQJT in the treatment of pancreatic β cell dysfunction.

Research progress on roles of autophagy regulating T lymphocyte function in the genesis and development of diseases / 中国肿瘤生物治疗杂志

@#[Abstract] Autophagy, as an important intracellular metabolic pathway, has been proved to be ubiquitous in many kinds of cells. Its functional impairment can easily cause lots of diseases, such as cancer, leukemia, liver disease, diabetes and heart disease. In particular, autophagy is important for the development, differentiation and regulation of immune function of T lymphocytes. Abnormal autophagy of T lymphocytes can cause immune dysfunction and lead to diseases, such as inflammation, infection and autoimmunity. In view of the important role of autophagy in regulating T lymphocyte function and disease, this article illustrates the research progress on autophagy regulating the homeostasis, survival, proliferation, senescence, metabolism, immune function of T lymphocytes and many diseases, including tumors, in recent years.