Neuroprotective connection between metformin in cerebral ischemiareperfusion injury through managing PI3KAkt process

Deficits in the clearance of amyloid β-protein (Aβ) play a pivotal role in the pathogenesis of sporadic Alzheimer's disease (AD). The roles of blood monocytes in the development of AD remain unclear. In this study, we sought to investigate the alterations in the Aβ phagocytosis function of peripheral monocytes during ageing and in AD patients. A total of 104 cognitively normal participants aged 22-89 years, 24 AD patients, 25 age- and sex-matched cognitively normal (CN) subjects, 15 Parkinson's disease patients (PD), and 15 age- and sex-matched CN subjects were recruited. The Aβ uptake by blood monocytes was measured and its alteration during ageing and in AD patients were investigated. Aβ1-42 uptake by monocytes decreased during ageing and further decreased in AD but not in PD patients. Aβ1-42 uptake by monocytes was associated with Aβ1-42 levels in the blood. Among the Aβ uptake-related receptors and enzymes, the expression of Toll-like receptor 2 (TLR2) was reduced in monocytes from AD patients. Our findings suggest that monocytes regulate the blood levels of Aβ and might be involved in the development of AD. The recovery of the Aβ uptake function by blood monocytes represents a potential therapeutic strategy for AD.Kcnq1 overlapping transcript 1 (kcnq1ot1), an imprinted antisense lncRNA in the kcnq1 locus, acts as a potential contributor to cardiovascular disease, but its role in atherosclerosis remains unknown. The aim of this study was to explore the effects of kcnq1ot1 on atherogenesis and the underlying mechanism. Our results showed that kcnq1ot1 expression was significantly increased in mouse aorta with atherosclerosis and lipid-loaded macrophages. Lentivirus-mediated kcnq1ot1 overexpression markedly increased atherosclerotic plaque area and decreased plasma HDL-C levels and RCT efficiency in apoE-/- mice fed a Western diet. Upregulation of kcnq1ot1 also reduced the expression of miR-452-3p and ABCA1 but increased HDAC3 levels in mouse aorta and THP-1 macrophages. Accordingly, kcnq1ot1 overexpression inhibited cholesterol efflux and promoted lipid accumulation in THP-1 macrophages. In contrast, kcnq1ot1 knockdown protected against atherosclerosis in apoE-/- mice and suppressed lipid accumulation in THP-1 macrophages. Mechanistically, kcnq1ot1 enhanced HDAC3 expression by competitively binding to miR-452-3p, thereby inhibiting ABCA1 expression and subsequent cholesterol efflux. Taken together, these findings suggest that kcnq1ot1 promotes macrophage lipid accumulation and accelerates the development of atherosclerosis through the miR-452-3p/HDAC3/ABCA1 pathway.BACKGROUND This retrospective study aimed to investigate the efficacy and safety of image-guided intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) combined with administration of paclitaxel liposomes and cisplatin for locally advanced stage IIB-IIIB cervical cancer at a single center in China. MATERIAL AND METHODS The clinical data of 126 patients with stage IIB-IIIB cervical cancer treated in our hospital were retrospectively analyzed. The patients were divided into the IMRT group (n=63) and the VMAT group (n=63). The short-term clinical efficacy, the incidence of adverse reactions, the quality-of-life score, and the changes in levels of T-lymphocyte subsets, serum inflammatory factors, and tumor markers were compared pre- and posttreatment between the 2 groups. RESULTS The clinical response rate was 90.5% and 96.8% in the IMRT group and the VMAT group, respectively; the difference was not statistically significant. After treatment, the levels of CD3⁺, CD4⁺, and CD4⁺/CD8⁺ subsets rose significantly, while the CD8⁺ level declined significantly in both groups compared with the pretreatment levels. After treatment, the levels of serum vascular endothelial growth factor, squamous cell carcinoma antigen, interleukin-8, tumor necrosis factor-a, carcinoembryonic antigen, and carbohydrate antigen 125 declined in both groups compared with pretreatment levels. After treatment, the Karnofsky performance scale score rose in both groups, and it was higher in the VMAT group than in the IMRT group. CONCLUSIONS IMRT and VMAT combined with paclitaxel liposomes and cisplatin have similar short-term clinical efficacy and long-term survival rates in the treatment of stage IIB-IIIB cervical cancer.BACKGROUND Drug-induced anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) should be suspected in patients on certain medications who present with inflammatory ocular, constitutional, pulmonary, and/or renal manifestations. Here, we present a case of propylthiouracil (PTU)-induced AAV presenting initially with red eye, and review important diagnostic and management considerations for this uncommon disorder. CASE REPORT A 34-year-old woman with hyperthyroidism taking PTU presented with red eye, later followed by fevers and hemoptysis. She was found to have episcleritis, diffuse alveolar hemorrhage, and microhematuria. The infectious diseases workup was unrevealing. Laboratory evaluations were notable for a high-titer perinuclear ANCA and elevated anti-myeloperoxidase antibodies. GLPG1690 price Renal function was normal. She was ultimately diagnosed with PTU-induced AAV. PTU was promptly discontinued and she was treated with pulse-dose methylprednisolone for 3 days, followed by prednisone 60 mg daily. A kidney biopsy revealed pauci-immune focal segmental necrotizing and crescentic glomerulonephritis. Given an allergy to methimazole, she underwent thyroidectomy and was ultimately treated with rituximab. Her steroid doses are progressively being tapered and she has complete resolution of symptoms. CONCLUSIONS PTU-induced AAV is a rare and serious condition. Our patient presented with ocular symptoms prior to more commonly recognized pulmonary and renal manifestations. Patients may have favorable outcomes if PTU is discontinued promptly, but patients with vital-organ involvement may require treatment with steroids and may need additional immunosuppression.
Endometriosis is a common gynecologic disease associated with systemic inflammation and atherogenic risk factors. Therefore, women with endometriosis may have increased cardiovascular risk.
We aimed to evaluate arterial stiffness using cardio-ankle vascular index (CAVI) in women with and without endometriosis.
We enrolled 44 patients with endometriosis and 76 age‑matched controls without endometriosis.Endometriosis was diagnosed based on histopathologic examination or magnetic resonance imaging. Arterial stiffness was evaluated using CAVI in all study participants.
No differences were observed between patients and controls in terms of age (median [interquartile range, IQR], 30 [24.25-5] years and 26 years [24-35] years, respectively), body mass index (median [IQR], 23.31 [20.82-24.98] kg/m2 and 23.74 [21.13-26.78] kg/m2, respectively), or waist circumference (median [IQR], 69 [64-75] cm and 72 [65-81.25] cm, respectively). C‑reactive protein levels were higher in women with endometriosis than in controls (median [IQR], 0.