The human islet amyloid polypeptide reduces hippocampal tauopathy and behavioral impairments in P301S mice without inducing neurotoxicity or seeding amyloid aggregation.

Recent evidence suggests that human islet amyloid polypeptide (h-IAPP) accumulates in the brains of Alzheimer's disease (AD) patients and may interact with Aß or microtubule associated protein tau to associate with the neurodegenerative process. Increasing evidence indicates a potential protective effect of h-IAPP against Aß-induced neurotoxicity in AD mouse models. However, a direct therapeutic effect of h-IAPP supplementation on tauopathy has not been established. Here, we found that long-term h-IAPP treatment attenuated tau hyperphosphorylation levels and induced neuroinflammation and oxidative damage, prevented synaptic loss and neuronal degeneration in the hippocampus, and alleviated behavioral deficits in P301S transgenic mice (a mouse model of tauopathy). Restoration of insulin sensitization, glucose/energy metabolism, and activated BDNF signaling also contributed to the underlying mechanisms. These findings suggest that seemly h-IAPP has promise for the treatment of neurodegenerative disorders with tauopathy, such as AD.

Double Insurance for OC: miRNA-Mediated Platinum Resistance and Immune Escape.

Ovarian cancer (OC) is still the leading cause of death among all gynecological malignancies, despite the recent progress in cancer therapy. Immune escape and drug resistance, especially platinum-based chemotherapy, are significant factors causing disease progression, recurrence and poor prognosis in OC patients. MicroRNAs(miRNAs) are small noncoding RNAs, regulating gene expression at the transcriptional level. Accumulating evidence have indicated their crucial roles in platinum resistance. Importantly, they also act as mediators of tumor immune escape/evasion. In this review, we summarize the recent study of miRNAs involved in platinum resistance of OC and systematically analyses miRNAs involved in the regulation of OC immune escape. Further understanding of miRNAs roles and their possible mechanisms in platinum resistance and tumor escape may open new avenues for improving OC therapy.

Stem cell-like memory T cells: A perspective from the dark side.

Much attention has been paid to a newly discovered subset of memory T (TM) cells-stem cell-like memory T (TSCM) cells for their high self-renewal ability, multi-differentiation potential and long-term effector function in adoptive therapy against tumors. Despite their application in cancer therapy, an excess of TSCM cells also contributes to the persistence of autoimmune diseases for their immune memory and HIV infection as a long-lived HIV reservoir. Signaling pathways Wnt, AMPK/mTOR and NF-κB are key determinants for TM cell generation, maintenance and proinflammatory effect. In this review, we focus on the phenotypic and functional characteristics of TSCM cells and discuss their role in autoimmune diseases and HIV-1 chronic infection. Also, we explore the potential mechanism and signaling pathways involved in immune memory and look into the future therapy strategies of targeting long-lived TM cells to suppress pathogenic immune memory.

Serum biochemical indicators of hepatobiliary function in dogs following prolonged anaesthesia with sevoflurane or isoflurane.

OBJECTIVE: To investigate the changes in serum enzymes considered as biochemical indicators of hepatobiliary function in dogs following 5 hours of anaesthesia with isoflurane (ISO) or sevoflurane (SEVO). STUDY DESIGN: Experimental randomized crossover study, with intervals of at least 15 days between successive treatments. ANIMALS: Eight healthy adult mongrel dogs, four male, four female, weight 13.6-21.6 kg. METHODS: Treatments consisted of anaesthesia with ISO or SEVO at 1 or 1.5 minimum alveolar concentration (MAC) delivered in oxygen. MAC was taken as 1.39% for ISO and 2.36% for SEVO. Anaesthesia was induced by mask then, after endotracheal intubation, maintained according to the treatment protocol using a small animal circle system. Cardiopulmonary monitoring was carried out. Venous blood samples, obtained by needle puncture, were taken at 24 hours and 2, 7 and 14 days post anaesthesia. Serum concentrations of total protein, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase, (LDH), alkaline phosphatase (ALP), gamma-glutamyltransferese and total bilirubin were measured. Changes with time and with treatment were compared by Friedman analysis, Wilcoxon Signed test and Kruskal-Wallis test as relevant. p- value < 0.05 was considered significant. RESULTS: Compared to base-line values, at 24 hours post-anaesthesia there were significant increases in AST, ALT, ALP and LDH following one or more of the treatments, but by 2 days residual changes were not significant. At 24 hours, AST for treatment 1.5 MAC ISO was higher than 1 MAC ISO (p < 0.002), and LDH higher for 1.5 MAC SEVO than 1 MAC SEVO. CONCLUSION AND CLINICAL RELEVANCE: Both ISO and SEVO, at concentrations used for clinical anaesthesia, produce transient moderate effects on some hepatobiliary enzyme concentrations in dogs.