RNA m5C methylation orchestrates BLCA progression via macrophage reprogramming.

Recently, epigenetics showed essential roles in tumour microenvironment (TME) and immunotherapy response, however, the functions of RNA 5-methylcytosine (m5C) modification in TME remains unknown. According to 13 m5C regulators, we evaluated 412 BLCA patients from The Cancer Genome Atlas (TCGA) database. The m5C score was constructed by unsupervised clustering analysis and principal component analysis (PCA) algorithms. Gene set variation analysis (GSVA), ESTIMATE algorithm, and immunohistochemical (IHC) staining were performed. Macrophage chemotaxis assay was used to assess the M2 macrophages. Among the 412 patients, the frequency of mutation was 13%. m5C regulators was expressed significantly in BLCA tissue compared with normal tissue. Then, two m5C methylation modification patterns were identified with dissimilar TME cell infiltration patterns. The C1 alteration pattern in the m5C cluster was connected with better survival. In addition, we found that NSUN6 was highly correlated with recruitment of macrophages via bioinformatics and IHC. Further experiment validated that NSUN6 promoted HDAC10 expression by mediating m5C methylation, inhibited the transcription of macrophage-associated chemokines and thus inhibited the recruitment of M2 macrophages. The m5C score constructed by m5C modification pattern showed that high m5C score group had a better prognosis. This study uncovered the significant roles of m5C modifications in modulating the TME and indicated that NSUN6 could inhibit the recruitment of M2 macrophages via m5C methylation, which provided novel insight into epigenetic regulation of TME and clinical suggestions for immunotherapeutic strategies.

Effect of dietary flaxseed oil on the prognosis of acute anterior cruciate ligament rupture: a randomized placebo-controlled trial.

OBJECTIVE: This study aimed to explore whether dietary flaxseed oil has effects on acute anterior cruciate ligament (ACL) rupture prognosis after surgical reconstruction. METHODS: Patients with primary acute ACL rupture diagnosed by magnetic resonance imaging and clinical examination were recruited at Quanzhou First Hospital Affiliated to Fujian Medical University and randomized to either the placebo group or the flaxseed oil group by computer-generated random numbers. Patients in the placebo group took six corn oil capsules daily, while patients in the flaxseed oil group took six flaxseed oil capsules daily. The outcomes were evaluated by specific scales. RESULTS: Compared to the placebo group, the flaxseed oil group showed significantly higher International Knee Documentation Committee (IKDC) score (P = 0.007) and total Knee Injury and Osteoarthritis Outcome Score (KOOS) (P = 0.0003) after two-year administration. Patients treated with flaxseed oil exhibited a significantly higher rate of return to sporting level before injury (P = 0.04) and a lower rate of occurrence of giving way (P = 0.04) than those in the placebo group. Patients with flaxseed oil showed significantly less severe adverse events on index knee (P = 0.047). CONCLUSION: The administration of dietary flaxseed oil enhanced the prognosis of acute ACL rupture.

HtrA2 is required for inflammatory responses in BMDMs via controlling TRAF2 stability in collagen-induced arthritis.

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterized by the destruction of cartilage and bone. The present study aims to investigate the role of HtrA serine peptidase 2 (HtrA2) in the collagen-induced arthritis. The expressions of HtrA2 were determined in the database BioGPS and bone marrow-derived macrophages (BMDMs). The populations of myeloid and lymphoid cells were determined in wild type and HtrA2 knockout (HtrA2MKO) mice using flow cytometry. In addition, the expressions of pro-inflammatory cytokines (Il6, Tnf, and Il1ß) were determined in the activated BMDMs from wild type (WT) and HtrA2MKO mice. STRING database was used to predict the interactive proteins of HtrA2 and Co-Immunoprecipitation was used to confirm these interactions. A collagen-induced arthritis model was established to investigate the effects of HtrA2 on the arthritis symptoms. It was found that HtrA2 reduction was associated with the activation of myeloid cells. Interestingly, HtrA2 deficiency did not affect the development of myeloid and lymphoid cells. Further studies demonstrated that HtrA2 deficiency suppressed the production of pro-inflammatory cytokines in BMDMs induced by lipopolysaccharide or CpG. Co-Immunoprecipitation results demonstrated that HtrA2 enhanced the stability of TNF receptor-associated factor 2 (TRAF2). HtrA2 participated in the activation of the inflammatory response in a collagen-induced arthritis model. In summary, HtrA2 modulates inflammatory responses in BMDMs by controlling TRAF2 stability in a collagen-induced arthritis mouse model.

Targeting long non-coding RNA HERC2P3 inhibits cell growth and migration in human gastric cancer cells.

Long non-coding RNAs (lncRNAs) have been implicated in tumor development and progression. The lncRNA HERC2P3, located on human chromosome 15q11.1-q11.2, is one of pseudogenes of HERC2 (an E3 ubiquitin protein ligase). Its role and expression are still unclear in cancer. In the present study, we investigated the effects of HERC2P3 on gastric cancer cell growth and migration via CCK-8 assays and Transwell assays in vitro and tumor-bearing mouse model in vivo. The results demonstrated that HERC2P3 silencing inhibited cell growth and migration, although it only had a weak effect on cell growth. Western blot analysis revealed that Akt phosphorylation level could be reduced when HERC2P3 was knocked down, indicating Akt signaling may be involved in the HERC2P3-mediated tumor development. In addition, we analyzed the expression of HERC2P3 through quantitative RT-PCR in 30 paired gastric cancer samples and found HERC2P3 was up-regulated in gastric adenocarcinoma tissues compared with corresponding non-tumor tissues. Taken together, our results demonstrate that the abrogation of HERC2P3 could suppress tumor cell growth and migration, with important implication for validating HERC2P3 as a potential target for human gastric cancer therapy.