CCR7信号通路与视网膜新生血管

视网膜新生血管性疾病是致盲的主要原因。趋化因子受体7(C-C chemokine receptor type 7, CCR7)可通过细胞外信号调节激酶(extracellular signal regulate kinase,ERK)通路促进血管内皮生长因子(vascular endothelial growth factor, VEGF)的表达,导致血管渗漏、血管内皮细胞增生以及新生血管形成等改变。趋化因子受体7的检测可指导视网膜新生血管性疾病的诊治。     

Hazard identification of cis/trans-zearalenone through the looking-glass

Among the food-related health issues, the presence of contaminants has a prominent role, due to the wide range of exogenous compounds that can occur in food commodities and to their large differences in structure and biological activity. A comprehensive assessment of the related risk is thus actually demanding in terms of time and facilities involved. In this context, the use of computational strategies can be an effective choice for supporting the hazard identification procedure at the early stage. In this work, we focused on the food contaminant zearalenone by comparing the trans and cis isomers, respectively the well-known mycoestrogen and its still largely understudied isomer. We estimated the possible effects exerted by human metabolism on the xenoestrogenicity of cis-ZEN by using a validated in silico strategy based on docking simulations and rescoring procedures. Similarly, the exploitation of the most promising enzymatic detoxifying routes designed for trans-ZEN – which relies on the enzyme lactono hydrolase from Clonostachys rosea – has been assessed for the cis-isomer as well. Our results showed that both isomers can act as functional analogues with respect to xenoestrogenic activity, and several cis-ZEN metabolites with high biological potential have been identified. On the contrary, in spite of the high degree of structural analogy, the cis isomer showed a pattern of interaction with the degrading enzyme in stark contrast with that observed for trans-ZEN. For these reasons, the outcomes presented herein strongly support the inclusion of cis-ZEN in further studies of occurrence, metabolism and bioactivity assessment, and suggest the need for a dedicated handling for the cis isomer in risk assessment studies.     

Paradoxical zinc toxicity and oxidative stress in the mammary gland during marginal dietary zinc deficiency

Zinc (Zn) regulates numerous cellular functions. Zn deficiency is common in females; ∼80% of women and 40% of adolescent girls consume inadequate Zn. Zn deficiency enhances oxidative stress, inflammation and DNA damage. Oxidative stress and inflammation is associated with breast disease. We hypothesized that Zn deficiency increases oxidative stress in the mammary gland, altering the microenvironment and architecture. Zn accumulated in the mammary glands of Zn deficient mice and this was associated with macrophage infiltration, enhanced oxidative stress and over-expression of estrogen receptor α. Ductal and stromal hypercellularity was associated with aberrant collagen deposition and disorganized e-cadherin. Importantly, these microenvironmental alterations were associated with substantial impairments in ductal expansion and mammary gland development. This is the first study to show that marginal Zn deficiency creates a toxic microenvironment in the mammary gland impairing breast development. These changes are consistent with hallmarks of potential increased risk for breast disease and cancer.     

不同胰升血糖素样肽1受体激动剂类药物心血管结局研究差异及其在临床治疗中的指导意义

动脉粥样硬化性心血管疾病(ASCVD)是T2DM患者重要的伴发疾病和主要死因。在DM新药研发规则的影响下,新型DM药物的心血管结局研究(CVOT)数据不断涌现。7项针对胰升血糖素样肽1受体激动剂(GLP-1 RA)类药物的CVOT,因研究目的不同,采用不同的研究设计来验证不同的科学假设,全面证明GLP-1 RA类药物心血管安全性的同时,显示出某些药物的心血管保护作用。GLP-1 RA类药物临床证据使其在DM管理中的地位上升,为DM患者高血糖管理和心血管疾病防治提供新的解决方案。