N6-methyladenosine (m6A) regulator expression pattern correlates with the immune landscape in lung adenocarcinoma.

Lung adenocarcinoma is the leading cause of tumor-related death. The tumor microenvironment (TME) may determine anti-tumor treatment responses. We focused on 23 m6A regulators, and analyzed m6A regulator expression patterns in 995 lung adenocarcinoma samples collected from 7 publicly available datasets. Two m6A clusters were identified, wherein gene clusters and m6A score were generated using unsupervised clustering and principal component analysis based on differentially expressed genes with prognostic significance. Further, three independent datasets from TCGA-LUAD and GEO were employed to validate the impact of m6A signatures and score. We found that m6A cluster 1 with high m6A score was associated with an inflamed TME, higher neoantigen and tumor mutation burden and improved response to immunotherapy. However, anti-tumor immunity cells were exhausted in high m6A score patients; thus, the prognosis of these patients was poor. Elucidation of m6A regulator expression pattern may facilitate the development of effective treatment strategies for lung adenocarcinoma.

Ferroptosis-related gene signature predicts prognosis and immunotherapy in glioma.

AIMS: Glioma is a highly invasive brain tumor, which makes prognosis challenging and renders patients resistant to various treatments. Induction of cell death is promising in cancer therapy. Ferroptosis, a recently discovered regulated cell death, can be induced for killing glioma cells. However, the prognostic prediction of ferroptosis-related genes (FRGs) in glioma remains elusive. METHODS: The mRNA expression profiles and gene variation and corresponding clinical data of glioma patients and NON-TUMOR control were downloaded from public databases. Risk score based on a FRGs signature was constructed in REMBRANDT cohort and validated in other datasets including CGGA-693, CGGA-325, and TCGA. RESULTS: Our results demonstrated that the majority of FRGs was differentially expressed among GBM, LGG, and NON-TUMOR groups (96.6%). Furthermore, the glioma patients with low-risk score exhibited a more satisfactory clinical outcome. The better prognosis was also validated in the glioma patients with low-risk score no matter to which grade they were affiliated. Functional analysis revealed that the high-risk score group was positively correlated with the enrichment scores for immune checkpoint blockade-related positive signatures, indicating the critical role of glioma immunotherapy via risk score. CONCLUSION: A novel FRGs-related risk score can predict prognosis and immunotherapy in glioma patients.

MicroRNA­146a/NAPDH oxidase4 decreases reactive oxygen species generation and inflammation in a diabetic nephropathy model.

The present study investigated the role of microRNA (miR)­146a in a diabetic nephropathy (DN) model, and its molecular mechanism. DN mice were given intraperitoneal injections of streptozotocin (55 mg/kg/day) for 5 consecutive days as an in vivo DN model. The HK­2 human kidney cell line were exposed to 45% D­glucose as an in vitro DN model. Firstly, it was demonstrated that miR­146a expression was inhibited and NAPDH oxidase 4 (Nox4) was increased in DN mice. In HK­2 cells, overexpression of miR­146a inhibited Nox4 protein expression and decreased reactive oxygen species (ROS) generation, oxidative stress and inflammation, and suppressed vascular cell adhesion molecule­1 (VCAM­1) and intracellular adhesion molecule­1 (ICAM­1) protein expression. Nacetylcysteine, a Nox4 inhibitor, was demonstrated to inhibit ROS generation, suppress VCAM­1 and ICAM­1 protein expression, and decrease oxidative stress and inflammation in HK­2 cells following overexpression of miR­146a. In conclusion, these results indicated that miR­146a/Nox4 decreases ROS generation and inflammation and prevents DN. Therefore, miR­146a may represent a novel anti­inflammatory and ­oxidative modulator of DN.

Effects of Artesunate prevent nephritis via the Toll­like receptor 4/nuclear factor­κB signaling pathway in rats.

The active ingredient in Artemisia carvifolia, artemisinin, may alleviate inflammation and toxicity. Artemisinin and its derivatives are first­line anti­malarial drugs currently, which have rapid effects on fever caused by malaria parasites with fewer side effects. The present study investigated the effects of Artesunate in a mouse nephritis model. Mice were injected intraperitoneally with 500 µl pristine to induce nephritis, and were treated with 28.8 mg/kg Artesunate. Subsequently, proteinuria, renal function, and tumor necrosis factor (TNF)­α and interleukin (IL)­6 levels were assessed to evaluate the effects of Artesunate on nephritis. Western blot analysis was used to measure the protein expression levels of α­smooth muscle actin (SMA), TLR4, myeloid differentiation primary response gene 88 (MyD88), NF­κB p65 and transforming growth factor (TGF)­ß1 to investigate the underlying mechanisms of Artesunate on nephritis. The results demonstrated that Artesunate reduced proteinuria and preserved renal function in nephritis mice. Artesunate attenuated TNF­α and IL­6 levels, suppressed α­SMA, TLR4, MyD88, NF­κB p65 and TGF­ß1 protein expression, and decreased caspase­3 activity in nephritis mice. These results indicated that the effects of Artesunate may prevent nephritis and inhibit inflammation via the TLR4/NF­κB signaling pathway in mice. Therefore, Artesunate may be a potential therapeutic agent to prevent nephritis.

[Survey of acupuncture and moxibustion for clinical treatment of renal diseases].

In order to understand survey of medication combined with acupuncture and moxibustion for clinical treatment of renal diseases, clinical application and the mechanisms of acupuncture and moxibustion for treatment of renal diseases were summarized by electric retrieval of literature from 1982 to 2007. It is indicated that acupuncture and moxibustion can increase human immunity, reduce urinary protein, improve renal function, antagonize the side-effects of glucocorticoid hormones, etc. and medication combined with acup-moxibustion has the advantages of convenience, lower cost, safety, no adverse effects, etc.