Lung cancer is the leading cause of cancer-related death throughout the world. We aimed to investigate the role of a novel microRNA-876-5p and its potential molecular target bone morphogenetic protein 4 (BMP-4), in the epithelial-mesenchymal transition (EMT) of lung cancer. Expressions of microRNA-876-5p and its potential target BMP-4 were analysed in lung cancer cells and patient tissues. Luciferase activity assay was conducted to verify direct targeting of microRNA- 876-5p to the 3'-UTR of BMP-4 mRNA. Migration, invasion capacities of lung cancer cells expressing microRNA-876-5p were analysed, and characteristics of lung cancer EMT protein markers were also evaluated. A xenograft tumour mouse model was established to address the roles of microRNA-876-5p and BMP-4 in lung cancer EMT . MicroRNA-876- 5p was decreased while BMP-4 was increased in lung cancer cells and tissues. MicroRNA-876-5p directly targeted 3'-UTR of BMP-4 mRNA to inhibit its expression. MicroRNA-876-5p expression significantly inhibited the migration, invasion and EMT of lung cancer cells, as well as metastasis , which required BMP-4 expression. MicroRNA-876-5p suppresses EMT of lung cancer by directly down-regulating BMP-4, both of which could serve as potential therapeutic targets in the treatment of lung cancer.

Objective Increasing evidence demonstrates that oxidative stress and inflammatory are involved in amyloid β (Aβ)-induced memory impairments. Ursolic acid (UA), a triterpenoid compound, has potent anti-inflammatory and antioxidant activities. However, it remains unclear whether UA attenuates Aβ-induced neurotoxicity. Method The aggregated Aβ25-35 was intracerebroventricularly administered to mice. Results We found that UA significantly reversed the Aβ25-35-induced learning and memory deficits. Our results indicated that one of the potential mechanisms of the neuroprotective effect was attenuating the Aβ25-35-induced accumulation of malondialdehyde (MDA) and depletion of glutathione (GSH) in the hippocampus. Furthermore, UA significantly suppressed the upregulation of IL-1β, IL-6, and tumor necrosis-α factor levels in the hippocampus of Aβ25-35-treated mice. Conclusion These findings suggest that UA prevents memory impairment through amelioration of oxidative stress, inflammatory response and may offer a novel therapeutic strategy for the treatment of Alzheimer’s disease.

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low-dose ipilimumab in advanced NSCLC. Here we evaluate this regimen as first-line treatment in special populations (cohort A1) and a reference population (cohort A; previously reported). Method: Patients had previously untreated advanced NSCLC. Cohort A1 (n¼198) had ECOG PS 2 or ECOG PS 0e1 with 1 of: asymptomatic untreated brain metastases, hepatic or renal impairment, or HIV. Cohort A (n¼391) had ECOG PS 0e1. Patients with known EGFR mutations or ALK translocations sensitive to available targeted therapy were excluded from both cohorts. Nivolumab 240 mg Q2W plus ipilimumab 1 mg/kg Q6W was administered for two years or until disease progression/unacceptable toxicity. Safety and efficacy endpoints were assessed; cohort A1 analyses were exploratory. Result: Cohort A1 patients were grouped as: ECOG PS 2 (n¼139) and all other special populations (AOSP; n¼59). Baseline characteristics were generally balanced between cohorts. Rates of grade 3e4 treatment-related adverse events (TRAEs) were similar between cohorts; within cohort A1, grade 3e4 TRAEs were numerically higher in AOSP versus the ECOG PS 2 subgroup; TRAEs leading to discontinuation were similar across populations (Table). ORR was 25% in cohort A1 (patients with ECOG PS 2, 20%; AOSP, 37%) and 35% in cohort A. PFS was numerically shorter in cohort A1 than cohort A; high TMB (10 mut/Mb) and higher PD-L1 expression (1% or 50%) were associated with numerically longer PFS in both cohorts (Table). Conclusion: First-line flat-dose nivolumab plus weight-based ipilimumab showed a consistent safety profile in special populations with advanced NSCLC, including those with ECOG PS 2. Patients with either high TMB or higher tumor PD-L1 expression appeared to exhibit improved efficacy.