Combination drug treatment prolongs survival of experimentally infected mice with silver-haired bat rabies virus

Rabies is a lethal disease in humans and animals, killing approximately 60,000 people every year. Currently, there is no treatment available, except post-exposure prophylaxis (PEP) that can be administered whenever exposure to a rabid animal took place. Here we describe the beneficial effects of a combination treatment initiated at day 4 post infection, containing anti-viral drugs and immune modulators in infected mice. Combination therapy resulted in significant increase in survival time (P < 0.05) and significantly lowers viral RNA in the brain and spinal cord (P < 0.05). Furthermore, treatment influenced markers of pyroptosis and apoptosis and early inflammatory response as measured by the levels of TNF-α. Morphological lesions were absent in rabies virus infected mice with few signs of inflammation. However, these were not significant between the different groups.     

超分子水杨酸治疗痤疮的效果及对皮肤屏障的影响

目的:观察超分子水杨酸对于痤疮的疗效及皮肤屏障的影响。方法:采用随机对照实验。选取痤疮患者40例,随机分为实验组和对照组,每组20例。实验组:给予30%超分子水杨酸换肤治疗,1周1次并配合外用特护霜,共治疗4次;对照组:仅每日给予特护霜外用。疗程结束4周后随访观察。治疗前及随访时使用CK无创皮肤检测仪检测两组患者面部皮肤生理指标,计数面部皮损。使用VISIA皮肤分析仪拍照留存。结果:实验组总有效率90%,对照组总有效率15%,两组比较有显著性差异(P<0.05)。同治疗前相比,实验组治疗后经皮水分丢失量(TEWL)、红斑值、角质层含水量及p H值均有改善,差异均有统计学意义(P<0.05)。与对照组比较,实验组治疗后TEWL、角质层含水量及p H值均有改善,差异均有统计学意义(P<0.05)。两组患者均未出现色素沉着、瘢痕等不良反应。结论:超分子水杨酸治疗痤疮疗效确切,同时具有修复皮肤屏障的作用。     

养血解毒方对银屑病角质形成细胞紧密连接的调节作用

目的:观察银屑病样小鼠皮损紧密连接蛋白中水闸蛋白(claduin-1,claudin-7),闭锁蛋白(occludin)的表达,明确养血解毒方对银屑病表皮通透屏障的修复作用,为养血解毒方治疗银屑病提供科学依据。方法:将C57BL/6J小鼠随机分为空白组、模型组、甲氨喋呤组、养血解毒方组,制备甲氨喋呤溶液、养血解毒方水煎剂对应灌胃干预,同时小鼠背部剃毛后给予咪喹莫特涂抹诱导银屑病样皮损模型。每日拍照记录皮损形态并对严重程度指数(PASI)评分;水油测试笔检测皮损表皮含水量;苏木素-伊红(HE)染色观察其病理改变、测量表皮厚度;免疫荧光法检测增殖相关的核抗原(Ki67);免疫组化法检测表皮兜甲蛋白(loricrin),真皮中CD3^+T淋巴细胞浸润和紧密连接蛋白claduin-1,claudin-7,occludin的表达;蛋白免疫印迹法(Western blot)检测皮损中claudin-7,occludin的表达。模拟银屑病皮损微环境,建立白细胞介素-17(IL-17,1 mg·L^-1)刺激的角质形成细胞(Hacat)模型,制作养血组分、解毒组分、养血解毒方喷干粉进行干预。采用细胞增殖毒性检测试剂盒-8(CCK-8)法检测药物对Hacat细胞的毒性;细胞免疫荧光法检测药物对角质形成细胞claudin-1,claudin-7,occludin表达的干预作用。结果:与模型组比较,养血解毒方可显著减轻小鼠银屑病样皮损表现,降低PASI评分及皮损表皮厚度(P<0.01),增加皮损区表皮水分含量(P<0.01),减少表皮ki67,loricrin的异常表达和真皮CD3+T细胞浸润(P<0.01),并增加紧密连接蛋白claudin-1,claudin-7,occludin的表达(P<0.05),增加紧密连接结构的完整性;体外研究发现,与模型组比较,养血解毒方组和养血组分组明显升高紧密连接蛋白claudin-1,claudin-7,occludin的表达(P<0.05);与模型组比较,解毒组分组蛋白表达水平无统计学差异。结论:养血解毒方通过调节角质形成细胞间紧密连接的表达抑制其异常的增殖分化过程,进一步恢复破坏的表皮通透屏障,可能是其治疗银屑病的作用机制之一。其中养血解毒方的养血组分对调节紧密连接的修复起主要作用。     

电离辐射致肠道急性损伤的中医病机探讨

电离辐射所致的肠道急性损伤在临床普遍存在,轻者出现纳差、食欲不振、消化不良;重者出现持续的腹痛腹泻,常伴黏液、脓血,肛门坠痛、里急后重,甚至出现梗阻、糜烂、溃疡、穿孔等症。结合电离辐射的中医病因学特点,电离辐射致肠道急性损伤的中医基本病机为:邪盛伤正,气血乏源,虚实夹杂;升降失常,泌别失职,传导失司;“热”“湿”“毒”“瘀”蕴结,损伤血络;屏障缺失,易于恶化。据证立法,方从法出,有的放矢,这不仅为电离辐射导致的肠道急性损伤寻找有效的中医药防治措施提供了理论依据,也进一步拓展了中医药理论的应用范围,因此具有重要的临床价值和实践意义。     

pH sensing in skin tumors: Methods to study the involvement of GPCRs,acid-sensing ion channels and transient receptor potential vanilloid channels

Solid tumors exhibit an inversed pH gradient with increased intracellular pH (pH_i) and decreased extracellular pH (pH_e). This inside-out pH gradient is generated via sodium/hydrogen antiporter 1, vacuolar-type H + ATPases, monocarboxylate transporters, (bi)carbonate (co)transporters and carboanhydrases. Our knowledge on how pH_e-signals are sensed and what the respective receptors induce inside cells is scarce. Some pH-sensitive receptors (GPR4, GPR65/TDAG8, GPR68/OGR1, GPR132/G2A, possibly GPR31 and GPR151) and ion channels (acid-sensing ion channels ASICs, transient receptor potential vanilloid receptors TRPVs) transduce signals inside cells. As little is known on the expression and function of these pH sensors, we used immunostainings to study tissue samples from common and rare skin cancers. Our current and future work is directed towards investigating the impact of all the pH-sensing receptors in different skin tumors using cell culture techniques with selective knockdown/knockout (siRNA/CRISPR-Cas9). To study cell migration and proliferation, novel impedance-based wound healing assays have been developed and are used. The field of pH sensing in tumors and wounds holds great promise for the development of pH-targeting therapies, either against pH regulators or sensors to inhibit cell proliferation and migration.