ABSTRACT
BACKGROUND: Epidemiological studies have revealed a correlation between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2D). Insulin resistance in the brain is a common feature in patients with T2D and AD. KAT7 is a histone acetyltransferase that participates in the modulation of various genes. AIM: To determine the effects of KAT7 on insulin patients with AD. METHODS: APPswe/PS1-dE9 double-transgenic and db/db mice were used to mimic AD and diabetes, respectively. An in vitro model of AD was established by Aß stimulation. Insulin resistance was induced by chronic stimulation with high insulin levels. The expression of microtubule-associated protein 2 (MAP2) was assessed using immunofluorescence. The protein levels of MAP2, Aß, dual-specificity tyrosine phosphorylation-regulated kinase-1A (DYRK1A), IRS-1, p-AKT, total AKT, p-GSK3ß, total GSK3ß, DYRK1A, and KAT7 were measured via western blotting. Accumulation of reactive oxygen species (ROS), malondialdehyde (MDA), and SOD activity was measured to determine cellular oxidative stress. Flow cytometry and CCK-8 assay were performed to evaluate neuronal cell death and proliferation, respectively. Relative RNA levels of KAT7 and DYRK1A were examined using quantitative PCR. A chromatin immunoprecipitation assay was conducted to detect H3K14ac in DYRK1A. RESULTS: KAT7 expression was suppressed in the AD mice. Overexpression of KAT7 decreased Aß accumulation and MAP2 expression in AD brains. KAT7 overexpression decreased ROS and MDA levels, elevated SOD activity in brain tissues and neurons, and simultaneously suppressed neuronal apoptosis. KAT7 upregulated levels of p-AKT and p-GSK3ß to alleviate insulin resistance, along with elevated expression of DYRK1A. KAT7 depletion suppressed DYRK1A expression and impaired H3K14ac of DYRK1A. HMGN1 overexpression recovered DYRK1A levels and reversed insulin resistance caused by KAT7 depletion. CONCLUSION: We determined that KAT7 overexpression recovered insulin sensitivity in AD by recruiting HMGN1 to enhance DYRK1A acetylation. Our findings suggest that KAT7 is a novel and promising therapeutic target for the resistance in AD.
ABSTRACT
OBJECTIVE: To assess the benefits of use of a tourniquet in one limb in patients undergoing simultaneous bilateral total knee arthroplasty (TKA). METHODS: A prospective randomized trial was designed to evaluate the outcomes of unilateral tourniquet use during simultaneous bilateral TKA. A total of 52 (36 women and 16 men) patients with osteoarthritis who underwent simultaneous bilateral primary TKA between January 2010 and January 2015 were assigned randomly to tourniquet (TG) or non-tourniquet (NG) groups prior to surgery. Operating time, pain score, range of motion, first active straight-leg raise time, swelling, wound healing, deep vein thrombosis, and Knee Society score were observed. RESULTS: Mean operating time in the TG group was shorter than that in the NG group (P < 0.05). Postoperative pain was measured by a visual analog scale (VAS) and straight-leg raise time, which was lower and shorter in limbs operated without the use of a tourniquet (P < 0.05). In addition, this group had less postoperative swelling and lower incidence of wound complications in the early postoperative period (P < 0.05). There was no significant difference in the range of motion (ROM), deep venous thrombosis incidence, and Knee Society scores between the two groups. CONCLUSIONS: Tourniquet use in bilateral TKA can reduce intraoperative time but was associated with a higher incidence of wound complications and larger postoperative knee swelling.
