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Background: Accumulating evidence suggests that matrix metalloproteinase (MMP) 12 plays a detrimental role in cerebro-cardiovascular diseases, including ischemic stroke (IS). Previous genome-wide association studies (GWAS) correlated the MMP12 rs660599 variant to IS risk in Europeans. However, this association is yet to be elucidated in the Chinese population. This study aims to assess the genetic predisposition of the MMP12 rs660599 G > A variant with regard to IS risk and short-term outcomes in individuals from Southern China. Methods: The Multiplex SNaPshot assay was used to genotype rs660599 in 1035 IS patients and 1061 age-matched healthy controls. Multivariate logistic regression analyses evaluated the effect of the rs660599 G > A polymorphism on IS susceptibility and short-term outcomes. Results: No significant association was found between the rs660599 G > A polymorphism and IS risk, even in dominant and recessive models. However, a relationship between rs660599 genotypes and diabetic status revealed that carriers of the A allele and the GA/AA genotype were more likely to develop IS. The presence of diabetes exacerbated the larger infarct volumes and elevated serum MMP12 levels seen in IS patients with the rs660599 A allele. The A allele of rs660599 and the GA/AA genotype were both correlated to moderate and severe stroke with poor short-term outcomes. Conclusion: The MMP12 rs660599 polymorphism is associated with a higher incidence of IS in people with diabetes and can serve as a biomarker for assessing the severity of IS and its short-term consequences. [ABSTRACT FROM AUTHOR]

Thought of as a metastasis‐associated gene, however, NME/NM23 nucleoside diphosphate kinase 4 (NME4) has rarely been described in the context of the tumour microenvironment. To understand the immunological implications of NME4 in oesophageal squamous cell carcinoma (ESCC), we used multiplex immunohistochemistry to analyse the clinicopathological and prognostic importance of NME4 expression. Then, after establishing a syngeneic tumour model with a C57BL/6 mouse strain that can recapitulate the tumour microenvironment of humans, we examined the immunological involvement of NME4 expression. To explore the underlying molecular mechanism, via quantitative proteomics and protein microarray screening, we investigated the potential signalling pathways involved. The clinicopathological and prognostic importance of NME4 expression is limited in ESCC patients. In vivo, single‐cell RNA sequencing showed that NME4 strikingly prevented CD8+ T cells from infiltrating the tumour microenvironment in murine ESCC. Mechanistically, we mapped out the NFκB2‐CCL5 axis that was negatively controlled by NME4 in the murine ESCC cell line AKR. Collectively, these data demonstrated that regulation of NFκB2‐CCL5 axis by NME4 prevents CD8+ T cells infiltration in ESCC. [ABSTRACT FROM AUTHOR]

Short for pyruvate kinase M2 subtype, PKM2 can be said of all‐round player that is notoriously known for its metabolic involvement in glycolysis. Holding a dural role as a metabolic or non‐metabolic (kinase) enzyme, PKM2 has drawn extensive attention over its biological roles implicated in tumor cells, including proliferation, migration, invasion, metabolism, and so on. wandering PKM2 can be transboundary both intracellularly and extracellularly. Specifically, PKM2 can be nuclear, cytoplasmic, mitochondrial, exosomal, or even circulate within the body. Importantly, PKM2 can function as an RNA‐binding protein (RBP) to self‐support its metabolic function. Despite extensive investigations or reviews available surrounding the biological roles of PKM2 from different angles in tumor cells, little has been described regarding some novel role of PKM2 that has been recently found, including, for example, acting as RNA‐binding protein, protection of Golgi apparatus, and remodeling of microenvironment, and so forth. Given these findings, in this review, we summarize the recent advancements made in PKM2 research, mainly from non‐metabolic respects. By the way, PKM1, another paralog of PKM2, seems to have been overlooked or under‐investigated since its discovery. Some recent discoveries made about PKM1 are also preliminarily mentioned and discussed. Highlights: Collating all the literatures related to PKM2, we found the following points that have rarely been summarized: PKM2 can be cytoplasmic, nuclear, mitochondrial, exosomal even circulating.PKM2 cameoed nuclear‐binding protein that binds with RNA.PKM2 can protect the Golgi apparatus.PKM2 can modulate the immune checkpoint expression. [ABSTRACT FROM AUTHOR]