Wound senescence: A functional link between diabetes and ageing?

Arguably, the two most important causes of pathological healing in the skin are diabetes and ageing. While these factors have historically been considered independent modifiers of the healing process, recent studies suggest that they may be mechanistically linked. The primary contributor to diabetic pathology is hyperglycaemia, which accelerates the production of advanced glycation end products, a characteristic of ageing tissue. Indeed, advanced age also leads to mild hyperglycaemia. Here, we discuss emerging literature that reveals a hitherto unappreciated link between cellular senescence, diabetes and wound repair. Senescent cells cause widespread destruction of normal tissue architecture in ageing and have been shown to be increased in chronic wounds. However, the role of senescence remains controversial, with several studies reporting beneficial effects for transiently induced senescence in wound healing. We recently highlighted a direct role for senescence in diabetic healing pathology, mediated by the senescence receptor, CXCR2. These findings suggest that targeting local tissue senescence may provide a therapeutic strategy applicable to a broad range of chronic wound types.     

Tier-based skin irritation testing of hair cleansing conditioners and their constituents

Purpose/Aim: The U.S. Food and Drug Administration (FDA) does not require specific testing to demonstrate the safety of personal care and cosmetic products or their ingredients. Recently, there have been reports of skin irritation associated with the use of commercially available cleansing conditioners. The goal of this study was to implement a tier-based safety assessment to evaluate the skin irritation potential of six commercially available cleansing conditioners and their ingredients.

Materials and Methods: The first tier of testing utilized the Organization for Economic Co-operation and Development (OECD) QSAR Toolbox to perform an in silico evaluation of the skin irritation potential of the product ingredients, and the second tier of testing utilized an OECD in vitro guideline test to evaluate the skin irritation potential of each product.

Results: Thirty-two ingredients were evaluated using the OECD QSAR Toolbox profiler for the tier one analysis; nine ingredients received a structural alert for skin irritation/corrosion. In the tier two in vitro analysis, the evaluated cleansing conditioner products were all classified as non-irritants.

Conclusions: These results provide evidence that use of the evaluated commercially available cleansing conditioners would not be expected to cause skin irritation among consumers. Additionally, this study demonstrates that the presence of structural alerts does not always accurately predict the safety of a product, as focused tier-based testing is necessary to comprehensively evaluate a product. This study illustrates a tier-based safety assessment approach, applicable to a wide variety of health endpoints, which efficiently and adequately evaluates the safety of personal care and cosmetic products and their ingredients.     

Forced Oxidative Degradation Pathways of the Imidazole Moiety of Daclatasvir

Daclatasvir hydrochloride (DCV) is the active pharmaceutical ingredient of Daklinza, a marketed product for the treatment of hepatitis C viral infection. The intrinsic stability of daclatasvir was evaluated via a forced degradation study. DCV was found to be stable in the solid state. In solution, its carbamate moiety is susceptible to basic hydrolysis, whereas its imidazole is liable to base-mediated autoxidation to form degradants 1 and 3, 7-8, respectively. The imidazole moiety can also be oxidized to form degradants 6-7 in the presence of hydrogen peroxide or azobisisobutyronitrile. The chloro-adduct degradant 9 was also observed in hydrogen peroxide solution. Furthermore, the imidazole moiety is sensitive to photodegradation in solution. Degradants 2-8 were observed in a solution of DCV exposed to high intensity light/UV light; the formation of degradants 2 and 5-8 was postulated through 4 degradation pathways. The degradants 3 and 4 were deemed to be secondary degradants of 7 and 5, respectively.     

Antimicrobial and antileukemic effects: in vitro activity of Calyptranthes grandifolia aqueous leaf extract

ABSTRACT

Natural products are still a promising source of bioactive molecules. Food and Drug Administration data showed that approximately 49% of the approved molecules originate naturally or chemically-resemble these substances, of which more than 70% are being used in anticancer therapy. It is noteworthy that at present there are no scientific studies to prove the effectiveness and safety of a number of plants used in folk medicine such as in the case of Calyptranthes grandifolia O. Berg (Myrtaceae) originally from South America. The aim of the present study was to determine the biological potential and toxicological effects of the aqueous leaf extract of C. grandifolia. The main detected phytoconstituents were condensed tannins and flavonoids and a high quantity of polyphenols. Regarding the antimicrobial potential, the extract exerted inhibitory activity against Pseudomonas aeruginosa. The results also revealed the extract induced DNA damage in a concentration-dependent manner in RAW 264.7 cells. In addition, C. grandifolia produced cytotoxicity in leukemia cell lines (HL60 and Kasumi-1) without affecting isolated human lymphocytes but significantly inhibited JAK3 and p38α enzyme activity. Taken together, these findings add important information on the biological and toxicological effects of C. grandifolia, indicating that aqueous extract may be a source of natural antimicrobial and antileukemic constituents.     

上市新型经皮递药系统的研究进展

对近几年来上市的经皮制剂进行文献整理和归纳，通过查阅相关文献，对贴剂、软膏剂、凝胶剂、乳膏剂、泡沫剂、洗剂等经皮给药制剂的特点、上市时间、作用、不良反应等进行总结。经皮制剂是药物通过皮肤吸收的一类外用递药给药系统，可以局部给药也可以全身给药，具有安全性高、毒副作用小、使用方便的优点，是目前国内外研究的热点。     

基于荧光定量PCR技术的当归不同炮制品中大肠埃希菌数量测定方法开发及比较研究

目的对当归不同炮制品中大肠埃希菌变化进行定量分析。方法建立荧光定量PCR方法,对当归不同炮制品、不同产地、不同收集企业、不同储藏时间的大肠埃希菌进行定量分析。结果不同炮制品中大肠埃希菌数量变化为生当归土炒当归酒当归;在不同产地的当归中以甘肃岷县地区所含的大肠埃希菌的数量最少;与零售企业相比,生产销售企业的当归和酒当归中大肠埃希菌的数量较少;不同储藏时间对当归和酒当归中大肠埃希菌数量有一定影响,随储藏时间的增加,大肠埃希菌的数量也在增加。对部分代表性样品进行平板计数法与荧光定量PCR法比较时发现,平板计数法结果多呈阴性,荧光定量PCR结果均呈阳性。结论所建立的荧光定量PCR法特异性、灵敏度、可靠性以及报告周期均优于平板计数法,可为当归不同炮制品中大肠埃希菌的快速、准确定量检测提供有效手段。     

皮肤晚期糖基化终产物无创检测技术在社区糖尿病早期筛查中的应用价值

目的评估皮肤晚期糖基化终产物(AGEs)无创检测技术在社区糖尿病早期筛查中的应用价值。方法于2018年1月至2019年1月选取社区健康体检、既往无糖尿病病史者701例,根据口服葡萄糖耐量试验(OGTT)结果分为正常糖耐量组443例、糖调节受损组198例和初诊糖尿病组60例。采用糖尿病无创检测技术对各组患者上臂皮肤AGEs进行检测,同时测定空腹血糖(FPG)、餐后2 h血糖(2 hPG)、糖化血红蛋白(HbA1c)、胰岛素、C肽、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、肌酐、尿素等指标。另将研究对象分为<45岁、45~59岁、≥60岁三个年龄段,比较不同糖调节状态人群在不同年龄段AGEs水平的变化。采用单因素方差分析比较各组间一般资料、生化指标及皮肤AGEs水平差异,并进行Pearson相关性分析和logistic回归分析。结果<45岁、45~59岁、≥60岁糖尿病前期和糖尿病患者AGEs值均高于正常糖耐量者(P<0.05)。皮肤AGEs水平与FPG和HbA1c相关(r=0.215、0.233,P<0.01)。AGEs是糖尿病前期和糖尿病风险的独立危险因素[优势比(95%可信区间):1.054(1.025~1.084)、1.116(1.071~1.163)]。糖尿病无创检测技术识别糖尿病的受试者工作特征(ROC)曲线下面积为0.721(95%可信区间:0.658~0.783),灵敏度为73.3%,特异度为61.3%;糖尿病无创检测技术识别糖尿病前期的ROC曲线下面积为0.601(95%可信区间:0.551~0.652),灵敏度为35.4%,特异度为87.1%。结论皮肤AGEs无创检测对评估糖尿病风险有一定应用价值,但可能不完全适用于糖尿病早期筛查。