Vellingsaleh7392

Neuronal excitotoxicity induces a plethora of downstream signaling pathways, resulting in the calcium overload-induced excitotoxic cell death, a well-known phenomenon in cerebrovascular and neurodegenerative disorders. The naturally occurring phytosterol, stigmasterol (ST) is known for its potential role in cholesterol homeostasis and neuronal development. However, the ability of ST to protect against the induced excitotoxicity in hippocampal neurons has not been investigated yet.

The present study aimed to investigate whether ST could protect against hypoxia/reoxygenation (H/R)-induced excitotoxicity in hippocampal neurons.

After H/R, neurons were initially subjected to trypan blue exclusion assay for the assessment of cell viability. Live staining using fluorescence dyes namely JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide), DCFDA (2',7'-dichlorofluorescein diacetate) and FM1-43 (N-(3-triethylammoniumpropyl)-4-(4-(dibutylamino)styryl) were used to measure MMP, ROS ed that ST interacted with the ligand binding domain of liver X receptor β (LXRβ), a known binding receptor of ST, through multiple hydrogen bonding.

Collectively, these findings revealed that ST exhibited a promising neuroprotective effect by regulating both pre- and post-synaptic events following H/R, particularly, attenuation of GluN2B-mediated excitotoxicity and oxidative stress, and induction of mitophagy, and suggested that ST might be a therapeutic promise against ischemic stroke and its associated neurological disorders.

Collectively, these findings revealed that ST exhibited a promising neuroprotective effect by regulating both pre- and post-synaptic events following H/R, particularly, attenuation of GluN2B-mediated excitotoxicity and oxidative stress, and induction of mitophagy, and suggested that ST might be a therapeutic promise against ischemic stroke and its associated neurological disorders.

Homocysteine (Hcy) induced vascular endothelial dysfunction is known to be closely associated with oxidative stress and impaired NO system. 1,8-Dihydroxy-3-methoxy-6-methylanthracene-9,10-dione (physcion) has been known to has antioxidative and anti-inflammatory properties.

The purpose of the present study was to define the protective effect of physcion on Hcy-induced endothelial dysfunction and its mechanisms involved.

Hyperhomocysteinemia (HHcy) rat model was induced by feeding 3% methionine. A rat thoracic aortic ring model was used to investigate the effects of physcion on Hcy-induced impairment of endothelium-dependent relaxation. Two doses, low (L, 30 mg/kg/day) and high (H, 50 mg/kg/day) of physcion were used in the present study. To construct Hcy-injured human umbilical vein endothelial cells (HUVECs) model, the cells treated with 3 mM Hcy. The effects of physcion on Hcy-induced HUVECs cytotoxicity and apoptosis were studied using MTT and flow cytometry. Confocal analysis was used to determine t candidate agent for the prevention of cardiovascular disease induced by Hcy.

The PACIFIC trial demonstrated that durvalumab significantly improved progression-free and overall survival (PFS/OS), versus placebo, in patients with Stage III NSCLC and stable or responding disease following concurrent, platinum-based chemoradiotherapy (CRT). A range of CT and RT regimens were permitted, and used, in the trial. We report post-hoc, exploratory analyses of clinical outcomes from PACIFIC according to CRT-related variables.

Patients were randomized 21 (1-42 days post-CRT) to up to 12 months durvalumab (10 mg/kg intravenously every 2 weeks) or placebo. Efficacy and safety were analyzed in patient subgroups defined by the following baseline variables platinum-based CT (cisplatin/carboplatin); vinorelbine, etoposide, or taxane-based CT (all yes/no); total RT dose (<60 Gy/60-66 Gy/>66 Gy); time from last RT dose to randomization (<14 days/≥14 days); and use of pre-CRT induction CT (yes/no). Treatment effects for time-to-event endpoints were estimated by hazard ratios (HRs) from unstrate factors in each subgroup preclude robust conclusions.

Durvalumab prolonged PFS and OS irrespective of treatment variables related to prior CRT to which patients with Stage III NSCLC had previously stabilized or responded. Limited patient numbers and imbalances in baseline factors in each subgroup preclude robust conclusions.

To characterize the benefit-risk profile of pemetrexed and platinum in combination with pembrolizumab in patients with non-squamous non-small cell lung cancer in the KEYNOTE-189 study, with reference to historical pemetrexed maintenance data from the PARAMOUNT, PRONOUNCE, and JVBL randomized studies.

To harmonize the treatment setting across the studies in our comparative analysis, we selected patients from KEYNOTE-189 who received ≥5 cycles of pemetrexed (pembrolizumab/pemetrexed/platinum, N = 310; placebo/pemetrexed/platinum, N = 135) and pooled data from PARAMOUNT (N = 359), PRONOUNCE (N = 98), and JVBL (N = 29) who received ≥5 cycles of pemetrexed (total, N = 486). For the 2 selected populations from KEYNOTE-189 and the pooled historical data, progression-free survival (PFS) was evaluated by Kaplan-Meier estimator and Cox proportional hazards model. Tumor response and grade ≥3 treatment-emergent adverse events (TEAEs) for the aforementioned population were summarized by descriptive statistics.

In thxed maintenance data.

Improved PFS was shown with pembrolizumab/pemetrexed/platinum compared with placebo/pemetrexed/platinum in the patient group with pemetrexed maintenance (≥5 cycles) in KEYNOTE-189. COTI-2 datasheet The PFS and safety profile of the control arm in KEYNOTE-189 were comparable with historical pemetrexed maintenance data.Photon-induced nuclear excitation (i.e. photo-excitation) can be used for production of nuclear isomers, which have potential applications in astrophysics, energy storage, medical diagnosis and treatment. This paper presents a feasibility study on photo-excitation production of four nuclear isomers (103mRh, 113m,115mIn and 176mLu) with intense γ-ray source based on laser-electron Compton scattering (LCS). The decay properties of these isomers and their potential applications in medical diagnosis and treatment were reviewed. The cross-section curve, simulated yield and activity of product of each photo-excitation process were calculated. The cutoff energy of LCS γ-ray beam was optimized by adjusting electron beam energy in order to maximize the isomer activity. It is found that the specific activity of the above-mentioned isomers can exceed ~0.2 GBq/g for 6-h target irradiation at an intensity of 1013 γ/s. Our simulation results suggest the prospect of producing medically interesting radionuclides with photo-excitation using the state-of-art LCS γ-ray beam facility.