Propofol upregulates miR-320a and reduces HMGB1 by downregulating ANRIL to inhibit PTC cell malignant behaviors

BackgroundOur previous study states that propofol suppresses proliferation and migration of papillary thyroid cancer (PTC) cells by downregulation of lncRNA ANRIL. This study intended to probe the downstream mechanism of ANRIL in PTC with potential microRNAs (miR) and genes.MethodsANRIL expression was detected in normal thyroid epithelial cells (Nthy-ori 3-1) and PTC cells (TPC-1, FTC-133, K1 and BCPAP). ANRIL expression was inhibited in TPC-1 and BCPAP cells to explore the effects of si-ANRIL in PTC malignant behaviors. The gain-and loss-of functions of ANRIL/miR-320a were performed to measure their roles in PTC. Levels of ANRIL, miR-320a, HMGB1, apoptosis- and Wnt/β-catenin and NF-κB pathways-related proteins were measured. Dual-luciferase reporter gene assay and RNA pull-down assay were applied to verify ANRIL/miR-320a/HMGB1 relation. si-ANRIL was transplanted into xenograft tumors in nude mice.ResultsANRIL was upregulated in TPC-1 and BCPAP cells. miR-320a targeted HMGB1, and ANRIL bound to miR-320a. In TPC-1 and BCPAP cells, si-ANRIL prevented PTC cell malignant behaviors, and inactivated the Wnt/β-catenin and NF-κB pathways; while si-ANRIL + miR-320a inhibition showed opposite trends. Overexpressing miR-320a promoted malignant behaviors of TPC-1 cells. In 6 μg/mL propofol-treated TPC-1 cells, miR-320a inhibition weakened propofol’s inhibitory effects on PTC cell growth. After ANRIL inhibition, the volume and weight of xenograft tumors were decreased.ConclusionPropofol upregulated miR-320a and reduced HMGB1 by downregulating ANRIL and inactivating the Wnt/β-catenin and NF-κB pathways, thus preventing PTC cell malignant behaviors. This study may offer new insights in PTC prevention and treatment.     

不同TGF-β表达量的hAMSCs尾静脉移植对异种周围神经移植小鼠坐骨神经功能的影响

目的探讨不同转化生长因子-β(TGF-β)表达量的人羊膜间充质干细胞(hAMSCs)尾静脉移植对异种周围神经移植小鼠坐骨神经功能的恢复作用。方法从健康剖宫产产妇志愿捐献的新鲜羊膜中分离出hAMSCs,并进行纯化及鉴定。构建上调和下调TGF-β表达的慢病毒质粒,并转染纯化的hAMSCs,构建出稳定的上调或下调TGF-β表达的hAMSCs。分离并剪去C57BL/6小鼠的部分坐骨神经,将SD大鼠的坐骨神经分离剪取并移植至小鼠的坐骨神经缺损处,构建出异种周围神经移植小鼠模型。将模型小鼠按随机数字表分为对照组、未修饰的hAMSCs治疗组、高表达TGF-β的hAMSCs治疗组、低表达TGF-β的hAMSCs治疗组,每组10只。各组于造模前1 d分别经尾静脉注射磷酸盐缓冲液或相应的hAMSCs重悬液进行移植治疗。于治疗后第14天时采用DigGait步态分析系统评估各组小鼠的坐骨神经功能恢复情况。结果治疗后第14天时,高表达TGF-β的hAMSCs治疗组小鼠的坐骨神经功能指数(-25.820±0.286)明显高于低表达TGF-β的hAMSCs治疗组(-33.413±0.920)和未修饰的hAMSCs治疗组(-30.755±0.421),差异均有统计学意义(P<0.05)。结论高表达TGF-β的hAMSCs尾静脉移植能够更有效地改善异种周围神经移植小鼠的坐骨神经功能,其可能成为周围神经损伤治疗的新突破口。     

Nano-curcumin therapy,a promising method in modulating inflammatory cytokines in COVID-19 patients

BackgroundAs an ongoing worldwide health issue, Coronavirus disease 2019 (COVID–19) has been causing serious complications, including pneumonia, acute respiratory distress syndrome (ARDS), and multi-organ failure. However, there is no decisive treatment approach available for this disorder, which is primarily attributed to the large amount of inflammatory cytokine production. We aimed to identify the effects of Nano-curcumin on the modulation of inflammatory cytokines in COVID-19 patients.MethodForty COVID-19 patients and 40 healthy controls were recruited and evaluated for inflammatory cytokine expression and secretion. Subsequently, COVID-19 patients were divided into two groups: 20 patients receiving Nano-curcumin and 20 patients as the placebo group. The mRNA expression and cytokine secretion levels of IL-1β, IL-6, TNF-α and IL‐18 were assessed by Real‐time PCR and ELISA, respectively.ResultOur primary results indicated that the mRNA expression and cytokine secretion of IL-1β, IL-6, TNF-α, and IL-18 were increased significantly in COVID-19 patients compared with healthy control group. After treatment with Nano-curcumin, a significant decrease in IL-6 expression and secretion in serum and in supernatant (P = 0.0003, 0.0038, and 0.0001, respectively) and IL-1β gene expression and secretion level in serum and supernatant (P = 0.0017, 0.0082, and 0.0041, respectively) was observed. However, IL-18 mRNA expression and TNF-α concentration were not influenced by Nano-curcumin.ConclusionNano-curcumin, as an anti-inflammatory herbal based agent, may be able to modulate the increased rate of inflammatory cytokines especially IL-1β and IL-6 mRNA expression and cytokine secretion in COVID-19 patients, which may cause an improvement in clinical manifestation and overall recovery.     

Knockdown of PVT1 inhibits IL-1β-induced injury in chondrocytes by regulating miR-27b-3p/TRAF3 axis

Long noncoding RNA plasmacytoma variant translocation 1 (PVT1) has been identified to implicate in the progression of osteoarthritis (OA). However, the mechanism underlying PVT1 in OA development remains largely unknown. This study aimed to investigate the effect of PVT1 on interleukin-1 beta (IL-1β)-induced injury in chondrocytes and explore potential mechanism. The cartilage tissues from 25 OA patients and normal controls were collected. Human transformed chondrocytes C28/I2 were stimulated by IL-1β. The levels of PVT1, microRNA (miR)-27b-3p, and tumor necrosis factor receptor-associated factor 3 (TRAF3) were detected by quantitative real-time polymerase chain reaction or western blot. IL-1β-induced injury was investigated by cell viability, apoptosis, autophagy and inflammatory response using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, flow cytometry, western blot and enzyme linked immunosorbent assay, respectively. The target association between miR-27b-3p and PVT1 or TRAF3 was explored by luciferase reporter, RNA immunoprecipitation and RNA pull-down assays. We found that PVT1 expression was enhanced in OA patients and IL-1β-treated C28/I2 cells. Silence of PVT1 promoted cell viability and autophagy but suppressed apoptosis and inflammatory response in IL-1β-treated C28/I2 cells. miR-27b-3p was confirmed as a target of PVT1 and its deficiency reversed the suppressive effect of PVT1 knockdown on IL-1β-induced injury. TRAF3 was a target of miR-27b-3p and attenuated the effect of miR-27b-3p on IL-1β-induced injury in C28/I2 cells. Moreover, TRAF3 expression was positively regulated by PVT1 via sponging miR-27b-3p. Collectively, knockdown of PVT1 increased cell viability and autophagy but inhibited apoptosis and inflammatory response in chondrocytes treated by IL-1β via up-regulating miR-27b-3p and down-regulating TRAF3.     

耳穴贴压联合中医饮食调护对糖尿病肾病患者的影响

目的:观察耳穴贴压联合中医饮食调护对糖尿病肾病患者的影响。方法:将糖尿病肾病患者60例按随机数字表法分成2组,对照组30例患者采用耳穴贴压治疗,观察组30例患者采用耳穴贴压联合中医饮食调护治疗。对比2组患者治疗前后肾功能指标、血清糖化血红蛋白、尿微量白蛋白、24h尿蛋白定量变化和肾小管损伤情况。结果:2组治疗后,血尿素氮(BUN)、内生肌酐清除率(CCr)、24 h尿白蛋白排泄率(UAE)和血肌酐(SCr)水平均明显优于治疗前,差异有统计学意义(P<0.05);治疗后,观察组肾功能指标BUN、CCr、UAE低于对照组,SCr则有所提高,差异有统计学意义(P<0.05)。2组患者治疗后,尿蛋白定量、尿微量白蛋白和血清糖化血红蛋白水平均明显优于治疗前,差异有统计学意义(P<0.05);观察组治疗后尿蛋白、尿微量白蛋白、血清糖化血红蛋白指标低于对照组,差异有统计学意义(P<0.05)。2组患者治疗后,β2-微球蛋白(β2-MG)和N-乙酰-β-D-氨基葡萄糖苷酶(NAG)水平均明显优于治疗前,差异有统计学意义(P<0.05);观察组治疗后肾小管损伤指标β2-MG、NAG低于对照组,差异有统计学意义(P<0.05)。结论:耳穴贴压联合中医饮食调护在糖尿病肾病患者中疗效明确,可改善肾功能指标,减轻肾小管损伤,改善临床症状。     

Potential anti-inflammatory effect of dapagliflozin in HCHF diet- induced fatty liver degeneration through inhibition of TNF-α, IL-1β, and IL-18 in rat liver

Non-alcoholic fatty liver (NAFLD) is accompanied by an increased expression of oxidative stress parameters, in addition to the inflammatory cytokines; tumor necrosis factor alpha (TNF-α), interleukin type 1beta (IL-1β), and interleukin type 18 (IL-18). The aim of this study is to investigate the effect of dapagliflizon (DAPA) on high carbohydrate-high fat (HCHF) diet-induced expression of inflammatory cytokines in rat liver. NAFLD was induced by feeding the rats HCHF diet (consist of animal fat tallow and standard show pellets) and the consumption of fructose in drinking water (10%) for 12 or 18 weeks. The oral administration of DAPA (1 mg/kg/day) from 13th week to 18th week significantly improved NAFLD as indicated by a significant reduction in liver aminotransferases in addition to a significant decrease of serum MDA, cholesterol, triglyceride and LDL-cholesterol with concomitant significant elevation of HDL-cholesterol. DAPA-treated animals showed a significant reduction of liver homogenate content of TNF-α, IL-1β, and IL-18. These results indicate that the administration of DAPA may be beneficial against HCHF diet-induced NAFLD. Histopathological examination of liver specimens supported the conclusion that DAPA improves steatohepatitis induced by HCHF diet.     

嘌呤配体P2X门控离子通道型受体7及其下游分子在痛风性关节炎中作用机制的研究进展

目前随着痛风性关节炎的发病率逐年上升,对该病炎性反应及疼痛机制的研究越来越多,该病主要由尿酸盐沉积及ATP刺激P2X7R、Nod样受体蛋白3、NEK7表达诱导炎性反应递质成熟与分泌所致,但具体机制尚不明确。现对P2X7R、NLRP3、NEK7的国内外研究进展进行综述,以探讨GA炎性反应及疼痛的发病机制,为防治GA提供新思路与治疗靶点。     

Wnt/β-Catenin Signaling Pathway as Chemotherapeutic Target in Breast Cancer: An Update on Pros and Cons

The Wnt/β-catenin pathway, in addition to playing a crucial role in the development of the mammary gland during embryogenesis and during pregnancy, is one of the most commonly altered pathways in breast cancer. Accumulating findings from in vitro and in vivo and clinical studies have been suggestive of this pathway as a potential chemotherapy target. However, approved chemotherapeutic agents targeting this pathway are still missing for the treatment of patients with cancer. None of the clinical trials on the Wnt/β-catenin pathway inhibitors have translated beyond phase I/II studies. Hence, detailed analysis of the alterations in this pathway and the therapeutic agents modulating Wnt/β-catenin signaling components in breast cancer is warranted. The present review explored the latest developments in the association of deregulation in the Wnt/β-catenin signal cascade with the pathogenesis of breast cancer, the progress in identifying the potential chemotherapeutic drugs inhibiting this pathway, and the status of these compounds in clinical trials of breast cancer.     

针灸联合龙胆泻肝汤对子宫脱垂患者血清TGF-β1、MMP-2、TIMP-2表达的影响

目的观察针灸联合龙胆泻肝汤治疗子宫脱垂的临床疗效及对患者血清TGF-β1、MMP-2、TIMP-2表达水平的影响。方法 296例子宫脱垂患者随机分为研究组和对照组,每组148例。对照组采用龙胆泻肝汤治疗,研究组在对照组的基础上采用针灸治疗。观察两组治疗前后的盆底功能障碍评分变化、盆底肌力评分变化及血清转化生长因子-β1 (TGF-β1)、基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶抑制剂-2(TIMP-2)表达水平变化,并比较两组临床疗效。结果研究组愈显率优于对照组(P<0.05)。两组治疗后盆底功能障碍评分较同组治疗前降低,研究组低于对照组,差异有统计学意义(P<0.05)。研究组治疗后盆底肌力评分高于对照组(P<0.05)。两组治疗后血清TGF-β1、MMP-2、TIMP-2表达水平与同组治疗前比较,差异有统计学意义(P<0.05);研究组治疗后血清TGF-β1、TIMP-2表达水平高于对照组(P><0.05),MMP-2表达水平低于对照组(P<0.05)。结论针灸联合龙胆泻肝汤能显著提高PDF患者的临床疗效,缓解患者的临床症状,改善患者血清TGF-β1、MMP-2、TIMP-2的表达水平。     

EZH2与β-catenin在骨肉瘤中的研究进展

果蝇Zeste基因增强子人类同源物2(enhancer of zeste homolog 2,EZH2)是多梳抑制复合物(polycomb repressor complex 2,PRC2)的催化核心蛋白,能够催化组蛋白3的27位赖氨酸的三甲基化(H3K27me3),然后沉默与细胞分化、抑制增殖相关基因的表达,导致肿瘤的发生。β-连环蛋白(β-catenin)作为经典Wnt/β-catenin信号通路上关键的效应分子,在细胞的生长及分化中发挥着重要作用,影响着肿瘤的形成。骨肉瘤是青少年常见的原发性恶性骨肿瘤,以往的研究证实EZH2和β-catenin都参与其中,但是二者在它的发生发展中是否存在关联,尚无研究报道。本文就EZH2及β-catenin在骨肉瘤中的研究进展作一综述。