The mechanism underlying arsenic-induced PD-L1 upregulation in transformed BEAS-2B cells.

Chronic exposure to arsenic promotes lung cancer. Human studies have identified immunosuppression as a risk factor for cancer development. The immune checkpoint pathway of Programmed cell death 1 ligand (PD-L1) and its receptor (programmed cell death receptor 1, PD-1) is the most studied mechanism of immunosuppression. We have previously shown that prolonged arsenic exposure induced cell transformation of BEAS-2B cells, a human lung epithelial cell line. More recently our study further showed that arsenic induced PD-L1 up-regulation, inhibited T cell effector function, and enhanced lung tumor formation in the mice. In the current study, using arsenic-induced BEAS-2B transformation as a model system we investigated the mechanism underlying PD-L1 up-regulation by arsenic. Our data suggests that Lnc-DC, a long non-coding RNA, and signal transducer and activator of transcription 3 (STAT3) mediates PD-L1 up-regulation by arsenic.

Homocysteine, vitamin B12, and folate levels in patients with multiple sclerosis in Chinese population: A case-control study and meta-analysis.

BACKGROUND: Current studies suggested discrepancies on the correlations between multiple sclerosis (MS) and blood levels of homocysteine (Hcy), vitamin B12 (VB12), and folate. We performed a case-control study and meta-analysis to help resolve the controversy of these lab values in Chinese patients with MS. METHODS: We recruited 80 Chinese MS patients, 86 age/sex matched neurological controls (patients with peripheral vertigo or sleep disorders), and 80 age- and sex-matched healthy controls. Serum Hcy levels were measured using flourimetric high-performance liquid chromatography, serum levels of VB12 and folate using immune assay. A literature search of PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed was conducted for case-control studies with pure Chinese populations published up to March 16, 2019. The effective size was estimated by the pooled standardized mean difference (SMD) and associated 95% confidence interval (CI). RESULTS: The case-control study results suggest higher Hcy levels (mean ± SD) and frequency of hyperhomocysteinemia in the Chinese MS cases than control groups (all p < 0.001), lower for VB12 levels (mean ± SD, p = 0.043 or 0.039). No significant difference was observed for levels of folate (mean ± SD, both p > 0.05), and for frequency of folate or VB12 deficiency (all p > 0.05). Analysis of pooled SMDs and 95% CIs suggested increased Hcy levels in Chinese MS patients (SMD: 2.31, 95% CI: 1.33-3.28, p < 0.001), and in relapsing or remitting cases relative to controls (SMD: 0.94 or 0.85, 95% CI: 0.49-1.39 or 0.35-1.34, both p < 0.001). The meta-analysis results also suggested reduced VB12 levels in Chinese MS patients (SMD: -0.30, 95% CI: -0.46-0.14, p < 0.001), and in relapsing MS patients compared to controls (SMD: -0.31, 95% CI: -0.47-0.15, p < 0.001), while no statistical difference for cases in remission. No significant difference was observed for levels folate in all comparisons. CONCLUSION: Patients with MS tend to have increased blood Hcy levels compared to controls. MS patients of Chinese origin and those in relapse may have decreased levels of VB12. Hcy and VB12 may contribute to pathogenesis of the disease, and VB12 may correlate with MS relapse.