Nashbyrd9988

This review will report the failures and side effects of many anti-Aβ drugs. In addition, emerging treatments targeting neuroinflammation in AD, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and receptor-interacting serine/threonine protein kinase 1 (RIPK1), that restore calcium dyshomeostasis and microglia physiological function in clearing Aβ plaques, respectively, will be deliberately discussed. Other novel pharmacotherapy strategies in treating AD, including disease-modifying agents (DMTs), repurposing of medications used to treat non-AD illnesses, and multi target-directed ligands (MTDLs) are also reviewed. These approaches open new doors to the development of AD therapy, especially combination therapy that can cater for several targets simultaneously, hence effectively slowing or stopping AD. ML355 Copyright © 2020 Husna Ibrahim, Yahaya, Mohamed, Teoh, Hui and Kumar.Myocardial contractile dysfunction in diabetic cardiomyocytes is a significant promoter of heart failure. Herein, we investigated the effect of icariin, a flavonoid monomer isolated from Epimedium, on diabetic cardiomyopathy (DCM) and explored the mechanisms underlying its unique pharmacological cardioprotective functions. High glucose (HG) conditions were simulated in vitro using cardiomyocytes isolated from neonatal C57 mice, while DCM was stimulated in vivo in db/db mice. Mice and cardiomyocytes were treated with icariin, with or without overexpression or silencing of Apelin and Sirt3 via transfection with adenoviral vectors (Ad-RNA) and specific small hairpin RNAs (Ad-sh-RNA), respectively. Icariin markedly improved mitochondrial function both in vivo and in vitro, as evidenced by an increased level of mitochondrial-related proteins via western blot analysis (PGC-1α, Mfn2, and Cyt-b) and an increased mitochondrial membrane potential, as observed via JC-1 staining. Further, icariin treatment decreased cardiac fibrogenesis (Masson staining), and inhibited apoptosis (TUNEL staining). Together, these changes improved cardiac function, according to multiple transthoracic echocardiography parameters, including LVEF, LVSF, LVESD, and LVEDD. Moreover, icariin significantly activated Apelin and Sirt3, which were inhibited by HG and DCM. Importantly, when Ad-sh-Apelin and Ad-sh-Sirt3 were transfected in cardiomyocytes or injected into the heart of db/db mice, the cardioprotective effects of icariin were abolished and mitochondrial homeostasis was disrupted. Further, it was postulated that since Ad-Apelin induced different results following increased Sirt3 expression, icariin may have attenuated DCM development by preventing mitochondrial dysfunction through the Apelin/Sirt3 pathway. Hence, protection against mitochondrial dysfunction using icariin may prove to be a promising therapeutic strategy against DCM in diabetes. Copyright © 2020 Ni, Lin, Huang, Lu, Sun, Zhang, Lin, Chi and Guo.Long non-coding RNAs (lncRNAs) are being found to play an increasingly important role in the development of tumors. However, their biological functions and the underlying mechanisms remain unclear. Using information from GEO Datasets, we found that the lncRNA LINC00588 was downregulated in osteosarcoma (OS) in bone but was upregulated in the metastatic tumor present in the lung. We assessed the function of LINC00588 using both overexpression and knock-out studies. We performed colony formation assay, CCK-8 assay, flow cytometry, wound healing assay, transwell assay, and RT-qPCR assay and used a xenograft model to investigate the influence of LINC00588 on cell proliferation, viability, cell apoptosis and cycle, migration, invasion, endothelial cell function, EMT (epithelial to mesenchymal transition), and tumor growth, respectively. Overexpression of LINC00588 appeared to inhibit cell proliferation, viability, migration, invasion, endothelial cell function, EMT, and tumor growth but not apoptosis, while we got the opposite result when we knocked down LINC00588. Next, we predicted that LINC00588 bound to miRNA-1972 and significantly downregulated its expression, which we then verified through a luciferase reporter assay. Subsequently, we knocked down miR1972 and performed CCK-8 and transwell assays to demonstrate that downregulation of miRNA-1972 could substantially inhibit the viability and invasion of osteosarcoma cells. The expression of TP53 was downregulated at the protein level but not at the mRNA level after the overexpression of miRNA-1972. Taken together, our findings indicate that LINC00588 plays a role in OS development by downregulating the expression of miRNA-1972, which can, in turn, inhibit the expression of TP53. Hence, we believe that the LINC00588/miRNA-1072/TP53 axis could potentially serve as a therapeutic target or diagnostic biomarker for osteosarcoma. Copyright © 2020 Zhou, Zhang, Liu, Song and Shao.Background Chronic stress has been known to impair the female reproductive function, but the mechanism remains to be further investigated. Chaiyu-Dixian Formula (CYDXF) has been reported to regulate human endocrine disorders clinically. However, whether this formula can affect chronic stress-induced ovarian follicular development is not clear. Aim of the study To examine effects of CYDXF on follicular development and explore possible mech anisms in a chronic unpredictable mild stress (CUMS) model. Materials and Methods Adult female rats were randomly divided into 5 groups control group, CUMS group (saline treatment), CUMS+Estradiol (E2) (0.1 mg/kg) group, CUMS+CYDXF (2.73 g/kg) group, and CUMS+CYDXF (5.46 g/kg) group. Body weights and behavioral tests were documented. Serum hormone levels were determined by enzyme-linked immunosorbent assay (ELISA). Western blotting was used to detect the protein levels in the PI3K/Akt pathway and brain-derived neurotrophic factor (BDNF). The follicles were analyzed and classified according to their morphological characterization. Results CYDXF relieved depression-like behaviors and ameliorated the abnormality in rat estrous cycle within the rat model of CUMS. Moreover, CYDXF could regulate endocrine disorders, increase the proportion of antral follicles as well as decrease the proportion of follicular atresia, which suggested that CYDXF could alleviate abnormal follicular development and improve overall ovarian function. Furthermore, CYDXF also activated the BDNF-mediated PI3K/Akt signaling pathway. Conclusions CYDXF (at dose of both 2.73 and 5.46 g/kg) attenuated chronic stress-induced abnormal ovarian follicular development by relieving depression-like behaviors and improving ovarian function through partly the regulation of the BDNF-mediated PI3K/Akt pathway. Copyright © 2020 Xu, Lin, Gong, Huo, Zhao, Zhu and Xi.