Loratadine augments emotional blushing

The aim of this study was to determine whether loratadine, a selective inverse agonist of peripheral histamine H₁ receptors, would reduce emotional blushing. Loratadine (10?mg) or placebo was administered orally one hour before 31 healthy participants sang a children's nursery rhyme to evoke embarrassment and blushing. Skin blood flow was monitored via a laser Doppler probe attached to the cheek. Increases in facial blood flow while participants sang were greater in the loratadine than the placebo group (mean increase?±?standard deviation 71?±?52% in the loratadine group versus 35?±?37%, p?=?.036). However, perceptions of blushing were similar in both groups. These findings suggest that loratadine augmented blushing rather than inhibiting it. Thus, histamine released during blushing may inhibit acute increases in facial blood flow by evoking H₁ receptor-mediated vasoconstriction.     

丹酚酸B调控pSmad3C/pSmad3L发挥抗肝纤维化-肝细胞癌作用

目的观察丹酚酸B(salvianolic acid B,Sal B)对二乙基亚硝胺(diethylnitrosamine,DEN)诱导小鼠肝纤维化-肝细胞癌进程的影响,并探讨Sal B经由p Smad3C/p21介导的抑癌信号、p Smd3L/PAI-1/c-Myc介导的促肝纤维化-肝癌信号转换机制。方法昆明种♂小鼠100只,随机分组,DEN诱导小鼠肝纤维化-肝细胞癌模型,不同剂量Sal B(15、30mg·kg^-1·d^-1,ig)及阳性药秋水仙碱(0.2 mg·kg^-1·d^-1,ig)干预。于造模第12周、第16周分批处死小鼠,肝脏活检,苏木精-伊红(HE)染色、Van Gieson(VG)染色观察肝组织病理学特征,Western blot法检测肝组织中p Smad3C、p S-mad3L、p21、纤溶酶原激活物抑制剂-1(plasminogen activator inhibitor 1,PAI-1)及c-Myc蛋白表达。结果正常组肝脏表面光滑、质地柔软,模型组第12周时肝脏表面粗糙、质地变硬,第16周时肝脏表面可见弥漫性结节、质地坚硬;而丹酚酸B干预组以上病变明显改善。HE及VG染色显示,正常组肝组织结构正常,模型组第12周时肝组织炎细胞浸润、胶原纤维增生,形成假小叶结构;第16周时肝小叶结构紊乱,细胞核变大、分裂相增多、异型性明显;Sal B干预组肝组织病变程度明显减轻。Western blot结果显示,正常组肝组织中p Smad3C、p Smad3L、PAI-1表达均较少,p21、c-Myc几乎不表达;模型组第12周时肝组织中p Smad3C无明显变化,p S-mad3L、PAI-1、p21表达增多,第16周时p Smad3C、p Smad3L、p21、PAI-1、c-Myc表达皆有增加;而Sal B干预组第12周时p Smad3C、p21表达明显增加,p Smad3L、PAI-1蛋白水平明显降低,第16周时p Smad3C表达明显增加,p21几乎无变化,p Smad3L、PAI-1、c-Myc表达明显降低。结论Sal B延缓DEN诱导的小鼠肝纤维化-肝细胞癌进程,其机制可能与调控p Smad3C/p21、p Smad3L/PAI-1/c-Myc信号转换有关。     

镇痛药物作用靶点的研究现状

疼痛是临床上的常见症状,也是当今困扰人类健康的严重问题之一,而控制疼痛是临床用药的主要方面之一。该文对现阶段已有的镇痛靶点及新型镇痛靶点进行简要的阐述,以期为新型、不良反应小、无耐受性、无成瘾性的镇痛药物的研究和开发,以及临床上的应用提供参考。     

Enzymatic glycosylation of oleanane-type triterpenoids

Abstract

Glycosylation is an effective approach to improve the druggability of natural products by increasing their water solubility. In this work, we report the glycosylation of oleanane-type triterpenoids by a recombinant microbial glycosyltransferase YjiC1. A preliminary screening test indicated YjiC1 exhibited robust capabilities for O-glycosylation of triterpenoids, based on LC/MS analysis. Among the products, two new compounds (2a and 3a), together with a known one (1a), were isolated and characterized. These products exhibited improved water solubility, and 3a showed moderate anti-HIV activities at 100 μM. This reaction provides a facile and efficient approach to synthesize the glucosides of triterpenoids.     

Comparison of Calorie-Restricted Diet and Resveratrol Supplementation on Anthropometric Indices,Metabolic Parameters,and Serum Sirtuin-1 Levels in Patients With Nonalcoholic Fatty Liver Disease: A Randomized Controlled Clinical Trial

Objective: There is a promising perspective regarding the potential effect of resveratrol in preventing and treating metabolic disturbances similar to that of calorie restriction. The aim of this study was to evaluate the effects of calorie-restricted (CR) diet on metabolic parameters and then to investigate whether resveratrol supplementation has beneficial effects similar to CR diet in patients with nonalcoholic fatty liver disease (NAFLD).

Methods: This randomized controlled clinical trial was conducted in 90 patients with NAFLD (males and females) aged 20 to 60 years with body mass index (BMI) ranging from 25 to 35 kg/m². Participants were assigned to one of three intervention groups as follows: The CR diet group (n = 30) received a prescribed low-calorie diet, the resveratrol group (n = 30) received 600 mg pure trans-resveratrol (2 × 300 mg) daily, and the placebo group (n = 30) received placebo capsules (2 × 300 mg) daily for 12 weeks. Fasting blood samples, anthropometric measurements, and dietary intake and physical activity data were collected for all participants at baseline and at the end of the trial.

Results: CR diet significantly reduced weight (by 4.5%); BMI; waist circumference; waist-to-hip ratio; and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lipid profiles in participants compared to resveratrol and placebo (all p < 0.05). Significant reductions in weight (by 1.1%) and BMI were found in the resveratrol group compared to the placebo group (p < 0.05). ALT, AST, and lipid profiles did not change significantly in the resveratrol group (all p > 0.05). No significant changes were seen in hepatic steatosis grade, serum glycemic parameters, and high-density lipoprotein cholesterol and sirtuin-1 levels in any group (all p > 0.05).

Conclusions: CR diet with moderate weight loss has favorable effects on NAFLD, and resveratrol supplementation induced weight loss but failed to mimic other aspects of CR diet. Future studies are warranted to evaluate the long-term and dose-dependent effects of resveratrol on metabolic diseases.     

川芎嗪联合顺铂对Lewis小鼠肺腺癌移植瘤与血管生成的影响

目的研究川芎嗪联合顺铂对Lewis肺腺癌小鼠移植瘤生长及抑制血管生成的作用机制。方法培养Lewis小鼠肺腺癌细胞,建立移植瘤模型。按照体重将成功制备的荷瘤小鼠模型随机分成4组,每组15只:模型组、顺铂组、川芎嗪组、联合组。模型组:0.9% NaCl,顺铂组:2 mg·kg^-1,川芎嗪组:100mg·kg^-1,联合组:两种药物相加。均每次0.2 mL,干预2周。称量瘤重,计算抑瘤率;用免疫组化方法检测每组血管内皮生长因子(VEGF)、血管抑制蛋白(VASH-1)的表达。结果给药后,联合组、顺铂组、川芎嗪组的抑瘤率分别为54.81%,32.36%,18.36%,与模型组(抑瘤率为0)比较,差异均有统计学意义(均P<0.05)。联合组、顺铂组、川芎嗪、模型组的VEGF表达分别为20.37±2.02,28.07±4.29,26.43±4.69,62.14±6.78;这4组的VASH-1表达分别为9.04±1.01,10.10±1.61,11.53±1.96,12.94±1.10,3个给药组与模型组相比,差异均有统计学意义(均P<0.05)。Pearson相关性分析:VEGF与VASH-1成正相关(r=0.664,P<0.05)。结论川芎嗪联合顺铂协同抑制Lewis小鼠移植瘤生长,其作用机制可能为川芎嗪与顺铂可以直接作用癌细胞,同时降低VEGF与VASH-1表达,发挥抗血管生成作用。     

Doxorubicin induces ZAKα overexpression with a subsequent enhancement of apoptosis and attenuation of survivability in human osteosarcoma cells

Human osteosarcoma (OS) is a malignant cancer of the bone. It exhibits a characteristic malignant osteoblastic transformation and produces a diseased osteoid. A previous study demonstrated that doxorubicin (DOX) chemotherapy decreases human OS cell proliferation and might enhance the relative RNA expression of ZAK. However, the impact of ZAKα overexpression on the OS cell proliferation that is inhibited by DOX and the molecular mechanism underlying this effect are not yet known. ZAK is a protein kinase of the MAPKKK family and functions to promote apoptosis. In our study, we found that ZAKα overexpression induced an apoptotic effect in human OS cells. Treatment of human OS cells with DOX enhanced ZAKα expression and decreased cancer cell viability while increasing apoptosis of human OS cells. In the meantime, suppression of ZAKα expression using shRNA and inhibitor D1771 both suppressed the DOX therapeutic effect. These findings reveal a novel molecular mechanism underlying the DOX effect on human OS cells. Taken together, our findings demonstrate that ZAKα enhances the apoptotic effect and decreases cell viability in DOX‐treated human OS cells.