Anti-inflammatory and anti-oxidant effects of aloe vera in rats with non-alcoholic steatohepatitis

BACKGROUND Aloe vera exerts several biological activities, such as, anti-inflammatory, antioxidant, and antimicrobial effects. It was recently shown to reduce insulin resistance and triglyceride level. We hypothesized that aloe vera would have beneficial effects in alleviating non-alcoholic steatohepatitis(NASH) in rats.AIM To examine the therapeutic effects of aloe vera in NASH rats.METHODS All rats were randomly divided into 3 groups(n = 6 in each group). Rats in the control group were fed ad libitum with a standard diet for 8 wk. Rats in the NASH group were fed ad libitum with a high-fat high-fructose diet(HFHFD) for 8 wk. Rats in the aloe vera group were fed ad libitum with a HFHFD and aloe vera in dimethylsulfoxide(50 mg/kg) by gavage daily for 8 wk. Liver samples were collected at the end of the treatment period.RESULTS Hepatic malondialdehyde(MDA) levels increased significantly in the NASH group as compared with the control group(377 ± 77 nmol/mg vs 129 ± 51 nmol/mg protein, respectively, P 0.001). Glutathione(GSH) levels were significantly lower in the NASH group than the control group(9 ± 2 nmol/mg vs 24 ± 8 nmol/mg protein, respectively, P = 0.001). The expression of interleukin-18(IL-18), nuclear factor-kappa β, and caspase-3 increased, while peroxisome proliferator-activated receptor gamma decreased in the NASH group compared with the controls. Following aloe vera administration, MDA levels decreased(199 ± 35 nmol/mg protein) and GSH increased(18 ± 4 nmol/mg protein) markedly. Steatosis, hepatocyte ballooning, lobular inflammation and increased hepatocyte apoptosis were observed in the NASH group. Aloe vera treatment attenuated these changes in liver histology.CONCLUSION Aloe vera attenuated oxidative stress, hepatic inflammation and hepatocyte apoptosis, thus improving liver pathology in rats with NASH.     

骶四针疗法配合盆底肌锻炼对产后压力性尿失禁患者盆底功能及性生活质量的影响

目的探讨骶四针疗法配合盆底肌锻炼对产后压力性尿失禁患者盆底功能及性生活质量的影响。方法选取2017年5月至2020年5月新疆医科大学第一附属医院收治的98例产后压力性尿失禁患者作为研究对象。采用随机数字表法分为研究组和对照组,各49例。两组均接受常规护理,对照组在常规护理的基础上给予盆底肌锻炼,研究组在对照组的基础上给予骶四针疗法,比较两组的临床疗效?1 h漏尿量?盆底肌力恢复情况及性生活情况。结果治疗后,研究组总有效率为91.84%,明显高于对照组的69.39%,差异具有统计学意义(P<0.05);与治疗前比较,治疗后两组1 h漏尿量减少,且研究组1 h漏尿量少于对照组,差异具有统计学意义(P<0.05);治疗后,两组盆底肌力分级均升高,且研究组盆底肌力分级高于对照组,差异具有统计学意义(P<0.05);治疗后,研究组性生活质量高水平比率为38.78%,高于对照组的20.41%,差异具有统计学意义(P<0.05)。结论骶四针疗法配合盆底肌锻炼用于产后压力性尿失禁患者,能改善患者的漏尿情况,提高其盆底肌力及性生活质量,临床疗效较好。     

金银花分子生物学研究进展

分子生物学(molecular biology)是从分子水平阐明生命现象和本质的科学,其发展为传统生药学的研究提供了新的生物技术和方法。金银花作为常用大宗药材之一,国内外学者在深入研究传统方法的基础上,采用分子生物学手段对其展开真伪鉴别、品质评价和控制等方面的相关研究,并取得了一定成果。该文主要综述了近年来分子生物学技术方法在金银花鉴别、有效成分生物合成的分子机制以及胁迫条件下次生代谢产物积累的分子机制研究,并针对基于杂交技术的标记(RFLP)、基于PCR的分子标记(RAPD,AFLP,SSR,ISSR)和基于DNA序列分析的SNP及DNA条形码对金银花的多样性识别、诊断、鉴定等方面进行了详细的总结,同时提出可以采用多组学技术,构建系统生物学技术和平台,建立次生代谢产物生物合成的相关模型,从而更好地研究金银花活性成分生物合成的分子机制以及药用植物在环境胁迫下的相关代谢产物的合成和积累等生命活动规律并进行调控,为进一步推动金银花现代化及其他中药资源的开发利用提供支撑与参考。     

P2Y13 and P2X7 receptors modulate mechanically induced adenosine triphosphate release from mast cells

Subcutaneous mast cells (MCs) are vulnerable to mechanical stimulation from external environment. Thus, MCs immune function could be modulated by their mechanosensitivity. This property has been identified as the trigger mechanism of needling acupuncture, a traditional oriental therapy. Previously we have demonstrated the release of adenosine triphosphate (ATP), a stress-responsive signalling molecule, from mechanical-perturbed MCs. The current work explores its underlying mechanisms. We noticed that propagation of intracellular free Ca²⁺ occurred among HMC-1 cells in response to 50% hypotonic shock. Additionally, amplifying cascade of ATP-induced ATP release was observed in RBL-2H3 cells stimulated by medium displacement, which could be mimicked by exogenous ATP (exoATP). Secondary ATP liberation induced by low level (50 nmol/L) of exoATP was reduced by inhibiting ecto-ATPase-dependent ADP production with ARL67156, or blocking P2 receptors with suramin or PPADS, or with specific P2Y₁₃ receptor antagonist MRS2211, or siRNA. Secondary ATP release induced by higher dose (200 μmol/L) of exoATP, sufficient to stimulate P2X₇ receptor, was attenuated by suramin, PPADS or specific P2X₇ receptor antagonist BBG, or siRNA. Finally, RT-PCR confirmed mRNA expression of P2Y₁₃ and P2X₇ in RBL-2H3 cells. Additionally, such secondary ATP release was attenuated by DPCPX, specific antagonist of adenosine A1 receptor, but not by MRS2179, specific inhibitor of P2Y₁ receptor. In summary, mechanosensitive ATP release from MCs is facilitated by paracrine/autocrine stimulation of P2Y₁₃ and P2X₇ receptors. This multi-receptor combination could mediate transmission of information from a local site to distal areas, enabling communication with multiple surrounding cells to coordinate and synchronize their function.     

NADPH oxidase inhibition rescues keratinocytes from elevated oxidative stress in a 2D atopic dermatitis and psoriasis model

Emerging evidence suggests oxidative stress plays a role in the pathophysiology of both atopic dermatitis (AD) and psoriasis (PSO). We established in vitro models of AD and PSO skin, and characterized these models in regard to their oxidative stress state. Both AD and PSO model keratinocytes exhibited elevated reactive oxygen species (ROS) levels and accumulated more DNA damage than control cells after oxidative stress induced by 250 µmol/L H₂O₂. Elevated ROS levels and DNA damage accumulation could be inhibited by the NADPH oxidase (NOX) inhibitor diphenyleneiodonium (DPI). Further, immunofluorescence analysis revealed the presence of both NOX1 and NOX4 in keratinocytes. By inhibiting NOX1, stress-related signalling cascades and elevated ROS levels could be abrogated, and survival of AD and PSO cells improved. Taken together, this study reveals that inhibition of NOX inhibition could abrogate elevated oxidative stress in a 2D model of AD and PSO.     

四君子汤合四磨汤加减治疗出口梗阻型便秘吻合器经肛门直肠切除术后的临床疗效

目的:观察四君子汤合四磨汤加减治疗出口梗阻型便秘(OOC)吻合器经肛门直肠切除术后(STARR)的临床疗效。方法:124例患者随机按数字表法分为对照组和观察组各62例。对照组术后给予芪蓉润肠口服液,20 mL/次/,3次/d;观察组术后给予四君子汤合四磨汤加减内服,1剂/d。两组疗程均连续治疗4周,并进行8周随访。分别于手术前、治疗后2周,4周、随访8周进行便秘主要症状评分和Longo ODS评分;于手术前和治疗后4周,进行超氧化物歧化酶(SOD),丙二醛(MDA)和便秘患者生存质量自评量表(PAC-QOL)评价,并进行肛门直肠测压,记录肛管静息压(ARP),肛管最大收缩压(MSP),直肠排便压力(RSP),初始感觉阈值(FSV),排便感觉阈值(CRS)和最大耐受容量(MTV)等指标;随访记录并发症发生率、复发率和排便正常率;术后4周进行满意度评价和安全性评价。结果:治疗后4周,观察组患者临床疗效优于对照组(Z=2.096,P0.05);治疗后2周,4周和随访8周,观察组便秘主要症状积分和Longo ODS评分均低于对照组(P0.01);观察组患者ARP,FSV,FSV,CRS均低于对照组(P0.01),MSP和RSP均高于对照组(P0.01);观察组并发症发生率、复发率分别为20.97%(13/62)和4.84%(3/62),分别低于对照组的39.71%(24/62)和16.13%(10/62)(P0.05);观察组排便正常率为91.94%(57/62),高于对照组的80.65%(50/62),组间差异无统计学意义;观察组PAC-QOL总分和各因子评分均低于对照组(P0.01);观察组SOD水平高于对照组,MDA水平低于对照组(P0.01);未发现干预中药相关不良反应。结论:四君子汤合四磨汤加减用于出口梗阻型便秘STARR术后患者,可进一步减轻便秘症状和病情程度,提高生活质量,降低术后并发症发生率和复发率,并可改善肛门直肠动力学指标和氧化应激指标,提高临床疗效。     

Damage-associated molecular pattern (DAMP) activation in melanoma: investigation of the immunogenic activity of 15-deoxy, Δ12,14 prostamide J2

Metastatic melanoma is the most deadly skin neoplasm in the United States. Outcomes for this lethal disease have improved dramatically due to the use of both targeted and immunostimulatory drugs. Immunogenic cell death (ICD) has emerged as another approach for initiating antitumor immunity. ICD is triggered by tumor cells that display damage-associated molecular patterns (DAMPs). These DAMP molecules recruit and activate dendritic cells (DCs) that present tumor-specific antigens to T cells which eliminate neoplastic cells. Interestingly, the expression of DAMP molecules occurs in an endoplasmic reticulum (ER) stress-dependent manner. We have previously shown that ER stress was required for the cytotoxic activity of the endocannabinoid metabolite, 15-deoxy, Δ^12,14 prostamide J₂ (15dPMJ₂). As such, the current study investigates whether 15dPMJ₂ induces DAMP signaling in melanoma. In B16F10 cells, 15dPMJ₂ caused a significant increase in the cell surface expression of calreticulin (CRT), the release of ATP and the secretion of high-mobility group box 1 (HMGB1), three molecules that serve as surrogate markers of ICD. 15dPMJ₂ also stimulated the cell surface expression of the DAMP molecules, heat shock protein 70 (Hsp70) and Hsp90. In addition, the display of CRT and ATP was increased by 15dPMJ₂ to a greater extent in tumorigenic compared to non-tumorigenic melanocytes. Consistent with this finding, the activation of bone marrow-derived DCs was upregulated in co-cultures with 15dPMJ₂-treated tumor compared to non-tumor melanocytes. Moreover, 15dPMJ₂-mediated DAMP exposure and DC activation required the electrophilic cyclopentenone double bond within the structure of 15dPMJ₂ and the ER stress pathway. These results demonstrate that 15dPMJ₂ is a tumor-selective inducer of DAMP signaling in melanoma.