Over the 6-month treatment period, NBP was effective for improving cognitive and global functioning in patients with subcortical vascular cognitive impairment without dementia and exhibited good safety.

Post-stroke depression (PSD) is the most prevalent psychiatric complication of acute ischemic stroke. The neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) are indicators of inflammation and are associated with stroke and depression. Therefore, the purpose of the present study was to examine the relationship between NLR/PLR and PSD. Retrospective analysis was carried out in 376 patients with first-ever acute ischemic stroke in the First Affiliated Yijishan Hospital of Wannan Medical College between March 2015 and September 2017. Patients were divided into PSD (n=104; 27.7%) and non-PSD (n=272; 72.3%) groups according to the Diagnostic and Statistical Manual of Mental Disorders-IV criteria at 6 months after stroke. Clinical data were collected retrospectively. NLR and PLR were acquired retrospectively from the routine blood tests performed at admission. A total of 120 healthy volunteers from the physical examination center in the First Affiliated Yijishan Hospital of Wannan Medical College were recruited as controls. Using logistic regression analysis, NLR (≥4.02) and PLR (≥203.74) were independently associated with PSD. NLR, odds ratio (OR) 3.926, 95% confidence intervals (CI, 2.365-7.947), P<0.001; PLR, OR 3.853, 95% CI (2.214-6.632), P=0.002. The ability of the combined index [area under the receiver operating characteristic curve, 0.701; 95% CI (0.622-0.780); P<0.001] to diagnose PSD was greater than that of either ratio alone. Higher NLRs and PLRs (≥4th quartile) were associated with PSD with a 5.79-fold (P<0.001) increase compared with lower levels of both. Higher NLRs and PLRs were found to be associated with depression 6 months after stroke, and the combined index was more meaningful than either alone in the early clinical detection of PSD.

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Upregulation of neuronal oxidative stress is involved in the progression of secondary brain injury (SBI) following intracerebral hemorrhage (ICH). In this study, we investigated the potential effects and underlying mechanisms of luteolin on ICH-induced SBI. Autologous blood and oxyhemoglobin (OxyHb) were used to establish in vivo and in vitro models of ICH, respectively. Luteolin treatment effectively alleviated brain edema and ameliorated neurobehavioral dysfunction and memory loss in vivo. Also, in vivo, we found that luteolin promoted the activation of the sequestosome 1 (p62)/kelch-like enoyl-coenzyme A hydratase (ECH)-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway by enhancing autophagy and increasing the translocation of Nrf2 to the nucleus. Meanwhile, luteolin inhibited the ubiquitination of Nrf2 and increased the expression levels of downstream antioxidant proteins, such as heme oxygenase-1 (HO-1) and reduced nicotinamide adenine dinucleotide phosphate (NADPH): quinine oxidoreductase 1 (NQO1). This effect of luteolin was also confirmed in vitro, which was reversed by the autophagy inhibitor, chloroquine (CQ). Additionally, we found that luteolin inhibited the production of neuronal mitochondrial superoxides (MitoSOX) and alleviated neuronal mitochondrial injury in vitro, as indicated via tetrachloro-tetraethylbenzimidazol carbocyanine-iodide (JC-1) staining and MitoSOX staining. Taken together, our findings demonstrate that luteolin enhances autophagy and anti-oxidative processes in both in vivo and in vitro models of ICH, and that activation of the p62-Keap1-Nrf2 pathway, is involved in such luteolin-induced neuroprotection. Hence, luteolin may represent a promising candidate for the treatment of ICH-induced SBI.

Though experimental evidence shows that human bone marrow-derived mesenchymal stem cells (hBMSCs) are able to suppress T-cell activation and proliferation, the precise mechanisms are still not completely understood. Here, we investigated the role of the negative costimulatory molecule B7-H4 in the immunosuppressive effect of hBMSCs on T-cell activation. We showed that B7-H4 expresses abundantly on hBMSCs assessed by reverse transcription, immunofluorescence staining, and flow cytometric analysis. Further studies demonstrated that B7-H4 expressed on hBMSCs inhibits T-cell activation and proliferation via induction of cell cycle arrest and inhibition of NF-kappaB nuclear translocation. Blocking B7-H4 would decrease the secretion of transforming growth factor-beta1 (TGF-beta1) in the supernatant of activated T cells co-cultured with hBMSCs. Addition of neutralizing antibodies against B7-H4 significantly attenuated the inhibitory effects of hBMSCs on T-cells. Thus, our study established the novel role of B7-H4 molecule in the suppressive effect of hBMSCs on T-cell activation and proliferation. Taken together, these results highlight the complex role of hBMSCs in regulating the immune response, asserting the possibility of their therapeutic application in transplantation, the treatment of graft-versus-host disease (GVHD), and autoimmune diseases.