补中益气汤调控JAK2/STAT3信号通路对气虚发热证大鼠肠道菌群、免疫功能及神经功能的影响

目的:分析补中益气汤调控Janus激酶2(JAK2)/信号传导与活化转录因子3(STAT3)/STAT3信号通路对气虚发热证大鼠肠道菌群、免疫功能及神经功能的影响。方法:将30只大鼠随机分为正常组、气虚发热模型组、补中益气汤组,每组10只。气虚发热模型组、补中益气汤组大鼠用于建立气虚发热模型,第18天开始,补中益气汤组给予补中益气汤灌胃治疗5 d,气虚发热模型组给予等体积蒸馏水。16SrRNA基因序列分析技术检测大鼠肠道菌群;ELISA法检测CD4⁺、CD8⁺、补体C3水平、免疫球蛋白G(IgG)、免疫球蛋白M(IgM)水平;放免法测定乙酰胆碱(Ach)、环磷酸腺苷(cAMP)和环磷酸鸟苷(cGMP)水平;蛋白质印迹法(Western blot)检测p-JAK2、p-STAT3蛋白表达水平。结果:补中益气汤可改善气虚发热所致的疣微菌门、互养菌门菌落减少,螺旋体门、埃普西隆杆菌门菌落增多情况(P<0.05)。补中益气汤可改善气虚发热所致的血清CD4⁺、C3、IgM、IgG水平及淋巴细胞转化率降低,血清CD8^...     

TrkC Is Essential for Nephron Function and Trans-Activates Igf1R Signaling

BackgroundInjury to kidney podocytes often results in chronic glomerular disease and consecutive nephron malfunction. For most glomerular diseases, targeted therapies are lacking. Thus, it is important to identify novel signaling pathways contributing to glomerular disease. Neurotrophic tyrosine kinase receptor 3 (TrkC) is expressed in podocytes and the protein transmits signals to the podocyte actin cytoskeleton.MethodsNephron-specific TrkC knockout (TrkC-KO) and nephron-specific TrkC-overexpressing (TrkC-OE) mice were generated to dissect the role of TrkC in nephron development and maintenance.ResultsBoth TrkC-KO and TrkC-OE mice exhibited enlarged glomeruli, mesangial proliferation, basement membrane thickening, albuminuria, podocyte loss, and aspects of FSGS during aging. Igf1 receptor (Igf1R)–associated gene expression was dysregulated in TrkC-KO mouse glomeruli. Phosphoproteins associated with insulin, erb-b2 receptor tyrosine kinase (Erbb), and Toll-like receptor signaling were enriched in lysates of podocytes treated with the TrkC ligand neurotrophin-3 (Nt-3). Activation of TrkC by Nt-3 resulted in phosphorylation of the Igf1R on activating tyrosine residues in podocytes. Igf1R phosphorylation was increased in TrkC-OE mouse kidneys while it was decreased in TrkC-KO kidneys. Furthermore, TrkC expression was elevated in glomerular tissue of patients with diabetic kidney disease compared with control glomerular tissue.ConclusionsOur results show that TrkC is essential for maintaining glomerular integrity. Furthermore, TrkC modulates Igf-related signaling in podocytes.     

Insulin Dependence Increases the Risk of Complications and Death in Total Joint Arthroplasty: A Systematic Review and Meta‐(Regression) Analysis

ObjectivesTo investigate the proportion of insulin‐dependent diabetes mellitus (IDDM) patients among diabetic patients undergoing total joint arthroplasty (TJA) and whether insulin dependence is associated with postoperative complications.MethodsA systematic literature search was performed in EMBASE, PubMed, Ovid, Medline, the Cochrane Library, Web of Science, the China Science and Technology Journal Database, and China National Knowledge Infrastructure from the inception dates to 10 September 2019. Observational studies reporting adverse events with IDDM following TJA were included. Primary outcomes were cardiovascular complications, pulmonary complications, kidney complications, wound complications, infection, and other complications within 30 days of surgery. Secondary outcomes were the proportion of IDDM patients among diabetic patients undergoing TJA and its time trend.ResultsA total of 19 studies involving 85,689 participants were included. Among patients undergoing TJA, 26% of diabetic patients had IDDM. Compared with non‐insulin‐dependent diabetes (NIDDM), the incidences of cardiac arrest (risk ratio [RR], 2.346; 95% confidence interval [CI], 1.553 to 3.546), renal failure (relative risk [RR], 2.758; 95% CI, 1.830 to 4.156), deep incisional surgical site infection (RR, 1.968; 95% CI, 1.107 to 3.533), wound dehiscence (RR, 2.209; 95% CI, 1.830 to 4.156), and death (RR, 2.292; 95% CI, 1.568 to 3.349) were all significantly increased in IDDM. A significant time trend was witnessed for the prevalence of IDDM (P = 0.014). There was no statistical significance for organ/space surgical site infection, thrombotic events (deep venous thrombosis/ pulmonary embolism), and revision rates.ConclusionInsulin‐dependent diabetes is an independent high‐risk factor for increased adverse outcomes relative to NIDDM, suggesting that hierarchical and optimal blood glucose management may contribute to reducing the adverse complications after surgery for these patients. In addition, because the risk of sepsis, deep wound infection, organ/space surgical site infection, urinary tract infection, renal insufficiency, and renal failure significantly increase after TJA in IDDM patients, more active postoperative antimicrobial prophylaxis may be needed on the premise of protecting renal function.     

Mechanisms linking gut microbial metabolites to insulin resistance

Insulin resistance is the rate-limiting step in the development of metabolic diseases, including type 2 diabetes. The gut microbiota has been implicated in host energy metabolism and metabolic diseases and is recognized as a quantitatively important organelle in host metabolism, as the human gut harbors 10 trillion bacterial cells. Gut microbiota break down various nutrients and produce metabolites that play fundamental roles in host metabolism and aid in the identification of possible therapeutic targets for metabolic diseases. Therefore, understanding the various effects of bacterial metabolites in the development of insulin resistance is critical. Here, we review the mechanisms linking gut microbial metabolites to insulin resistance in various insulin-responsive tissues.     

Rapid rise in plasma glucagon induced by acute cold exposure in man and rat

The effect of acute cold exposure on the concentration of glucagon in the blood was investigated in man and in intact and adrenalectomized rats.In man fasted overnight acute cold exposure, which caused a twofold increase in O₂-consumption resulted in a rapid rise in plasma glucagon. The levels of insulin and blood glucose remained unaltered, while the concentration of serum free fatty acids and -hydroxybutyrate increased.In fasted intact rats acute cold exposure lead to similar effects. A close parallelism between the rise in plasma glucagon and the concentration of hepatic cycloAMP was observed. Adrenalectomy did not impair the cold induced rise in plasma glucagon and hepatic cycloAMP.It is concluded that acute cold exposure caused a rapid rise in the concentration of plasma glucagon leading to an increase in the concentration of hepatic cycloAMP, thus enhancing the rate of hepatic gluconeogenesis and ketogenesis. As these alterations were similar in the absence of glucocorticoids and medulla-derived catecholamines, it is suggested that glucagon may play a role in the metabolic adaptation to acute cold exposure.     

Clonally restricted insulin autoantibodies in a cohort of 2200 healthy blood donors

Summary Serum samples of 2200 blood donors were screened for anti-insulin IgG by enzyme-linked immunosorbent assay. Specificity of detected antibodies was verified by competition with an excess of insulin and observation that saturated anti-insulin IgG were no longer measurable. The upper limit of measured signal in the population was defined as the mean plus three SD. In the direct assay, 32 sera were positive. Among these, 22 (1%) contained saturable insulin antibodies (true positive) and 10 were non-saturable and considered as non-insulin-specific. The positive blood donors were requested to answer a questionnaire and according to their answers, none had ever received insulin, was a first degree relative of a Type 1 (insulin-dependent) diabetic patient or had experienced a hypoglycaemic episode. None of the 22 true positive sera detected by enzyme-immunosorbent assay bound ¹²⁵-I-insulin to any significant extent. The nine sera yielding the highest signal were further characterized with regard to heavy and light chains as well as species specificity of ligand. Anti-insulin IgG from healthy blood donors contained only one heavy (1 2/9; 3 7/9) and one light ( 8/9; 1/9) chain. Three sera were human insulin specific; two were non-species-specific; the other four bound insulin in the order human = porcine > bovine. These results indicate that low affinity clonally restricted antibodies against insulin are present in unselected blood donors with a prevalence of 1%.     

吡啶斯的明试验对评价垂体hGH储备功能的价值

垂体hGH分泌受中枢神经介质调控。兴奋胆碱能系统可使hGH增加。本文试用胆碱酯酶抑制剂吡啶斯的明兴奋hGH,并与胰岛素兴奋试验进行比较,观察了13名正常青少年和10名垂体性侏儒症患者对两种兴奋试验的反应。结果显示口服吡啶斯的明2mg/kg体重能迅速有效地兴奋垂体hGH释放。其作用较胰岛素兴奋试验更强,是一项值得推荐的判定青少年垂体hGH储备功能的试验。     

Plasma membrane-mediated nuclear uptake and chromatin binding of insulin in tumor cell lines

Analysis of different cellular fractions after incubation of SW 948 and SW 707 colorectal carcinoma cells or WM 266-4 melanoma cells with 125I-insulin revealed the nondegraded hormone in the chromatin of these cells. Nuclear 125I-insulin was bound to specific fragments of EcoRI-, HaeIII-, and HincII-digested chromatin. A 45-kDa chromatin protein species that binds 125I-insulin was identified. Actinomycin D and cycloheximide inhibited the insulin-stimulated expression of chromatin receptors. Uptake of 125I-insulin by isolated nuclei occurred only in the presence of plasma membranes. Thus, at least some effects of insulin on target cells can be explained by direct gene regulation instead of "second messenger" action.