The different roles of selective autophagic protein degradation in mammalian cells

Autophagy is an intracellular pathway for bulk protein degradation and the removal of damaged organelles by lysosomes. Autophagy was previously thought to be unselective; however, studies have increasingly confirmed that autophagy-mediated protein degradation is highly regulated. Abnormal autophagic protein degradation has been associated with multiple human diseases such as cancer, neurological disability and cardiovascular disease; therefore, further elucidation of protein degradation by autophagy may be beneficial for protein-based clinical therapies. Macroautophagy and chaperone-mediated autophagy (CMA) can both participate in selective protein degradation in mammalian cells, but the process is quite different in each case. Here, we summarize the various types of macroautophagy and CMA involved in determining protein degradation. For this summary, we divide the autophagic protein degradation pathways into four categories: the post-translational modification dependent and independent CMA pathways and the ubiquitin dependent and independent macroautophagy pathways, and describe how some non-canonical pathways and modifications such as phosphorylation, acetylation and arginylation can influence protein degradation by the autophagy lysosome system (ALS). Finally, we comment on why autophagy can serve as either diagnostics or therapeutic targets in different human diseases.     

Lethal consequences of home cot modification

Sleeping accidents are a particular risk for infants and young children as they lack an understanding of potentially dangerous situations and are unable to self-extricate. These situations may result in deaths from asphyxia. While safety campaigns have focused on the faulty design of cots that are available for sale, modification of cots at home represents another potential problem area. A 17-month-old girl was found dead with her head wedged between the top side rail of her cot and a broomstick, which had been attached in an attempt to raise the height of the cot side. Death was due to neck compression from head entrapment. This case demonstrates that infant and toddler safe sleeping programmes should alert carers to the potential dangers of structurally altering cots or beds. Home modifications may create dangerous gaps that could result in entrapment with lethal neck compression; such alterations should be carefully assessed and documented by forensic death scene investigators.     

Pharmacotherapy for knee osteoarthritis: current and emerging therapies

ABSTRACT

Introduction

Osteoarthritis (OA) is the leading cause of pain, loss of function and disability in the elderly, with the knee being the most impactful joint affected. Currently, there is still no ‘cure’ in OA treatment.     

脂肪和肥胖相关基因通过TLR2/p38信号通路促进异位子宫内膜间质细胞纤维化

目的：探讨脂肪和肥胖相关基因（FTO）对异位子宫内膜间质细胞（eESCs）纤维化的影响及其机制。方法：采用实时定量聚合酶链反应（qRT-PCR）检测子宫内膜异位症（EMs）患者病变组织中m6A相关基因的表达；通过慢病毒载体过表达FTO，在eESCs中检测纤维化相关基因的表达；通过m6A2 Target数据库和MeRIP-qPCR预测和验证eESCs中FTO与Toll样受体2（TLR2）的关系；Western blot法检测p38的蛋白表达变化。结果：FTO在EMs中表达下调（P ＜0.05）；FTO过表达促进eESCs纤维化并抑制其增殖（P ＜0.05）；在eESCs中，FTO通过TLR2 的m6A修饰途径上调其蛋白水平（P ＜0.05）；FTO在eESCs中经TLR2/p38 信号通路促进细胞纤维化（P ＜0.05）。结论：FTO在EMs中低表达，上调FTO可能通过TLR2/p38信号通路促进eESCs纤维化。     

Health Implications and Counseling Considerations for Individuals With Piercings and Tattoos

Body art has become common and mainstream. Tattoos and body piercings represent highly individual expressions of identity and personal values. Health care services are enhanced when clinicians understand the anatomy and physiology, common discomforts, and real but rare serious risks of body modification and are prepared to provide compassionate support for individuals’ choices. Special consideration must be given to the needs of childbearing women. By opening channels of communication, clinicians can engage with clients in shared decision making to help those who possess or desire body art take steps to reduce the risk of adverse effects and obtain prompt and effective medical care when problems arise. Through respectful discussion of existing body art, the therapeutic relationship is strengthened, and greater insight into an individual’s health needs may be achieved.