Matrix remodeling associated 7 (MXRA7) was first noted to co-express with a group of matrix remodeling related genes, and its biological functions had remained unclear. In this study, we investigated the presumed function of MXRA7 in a carbon tetrachloride (CCl4)-induced acute liver injury model in mice. Wild-type, MXRA7−/− mice, and mice that were pulsed with hydrodynamic injection of vehicle or MXRA7-harboring plasmids were challenged with a single dose of CCl4 for injury induction. The sera, spleens, and livers were harvested from mice for assay of cytokines/chemokines expression, cellular responses, or histological features. We found that MXRA7 deficiency alleviated, and MXRA7 overexpression aggravated liver damage in CCl4-challenged mice. FACS analysis showed that MXRA7 deficiency reduced the recruitment of neutrophils through downregulation the expression of CXCL1 and CXCL2 in liver, decreased the number of CD8+ T cells in liver and spleen, suppressed the release of IFNγ and TNFα from T cells, and decreased IFNγ in serum and liver. Western blot assay demonstrated that MXRA7 deficiency suppressed the activation of MAPK pathway and AKT/NF-κB pathway, respectively. Lastly, MXRA7 deficiency or overexpression regulated the expression of two matrix remodeling-related genes (fibronectin and TIMP1) in the liver. We concluded that MXRA7 was an active player in CCl4-induced liver injury, hypothetically by mediating the inflammation or immune compartments and matrix remodeling processes. Further exploration of MXRA7 as a possible new therapeutic target for management of inflammation-mediated liver injury was discussed.
Kinesin family member 11 (KIF11) is a plus end‐directed kinesin indispensable for the formation of the bipolar spindle in metaphase, where it objects to the action of minus end‐directed molecular motors. Here, we hypothesize that
KIF11
might be a therapeutic target of breast cancer and regulated by
miR‐30a
. Cell Counting Kit 8 assays were used to investigate cell proliferation. Invasion assays were used to survey the motility of cells. Kaplan‐Meier and Cox proportional analyses were employed for this outcome study. The prognostic significance and performance of
KIF11
were validated on 17 worldwide independent microarray datasets and two The Cancer Genome Atlas‐Breast Invasive Carcinoma sets. microRNA was predicted targeting
KIF11
through sequence alignment in
microRNA.org
and confirmed by coexpression analysis in human breast cancer samples. Dual‐luciferase reporter assays were employed to validate the interaction between
miR‐30a
and
KIF11
further. Higher
KIF11
mRNA levels and lower
miR‐30a
were significantly associated with poor survival of breast cancer patients. Inhibition of
KIF11
by small‐hairpin RNA significantly reduced the proliferation and invasion capabilities of the breast cancer cells. Meanwhile, downregulation of
KIF11
could enhance the cytotoxicity of adriamycin in breast cancer cell lines MCF‐7 and MDA‐MB‐231. A population study also validated that chemotherapy and radiotherapy significantly improved survival in early‐stage breast cancer patients with low
KIF11
expression levels. Further bioinformatics analysis demonstrated that
miR‐30a
could interact with
KIF11
and validated by dual‐luciferase reporter assays. Therefore,
KIF11
is a potential therapeutic target of breast cancer.
miR‐30a
could specifically interact with
KIF11
and suppress its expression in breast cancer.
Aim: The aim of the study was to evaluate the potential predictive value of permanent RBBB and LBBB for longer-term prognosis in patients with new-onset STEMI who underwent percutaneous coronary intervention (PCI).Methods: Patients with new-onset STEMI that underwent emergency PCI at our department from June 2012 to September 2020 were included in the study. Gensini score (GS) was employed to evaluate the severity of coronary lesions. The primary endpoint of the study was the occurrence of major adverse cardiac and cerebrovascular events (MACCEs), the composite of cardiac mortality, recurrence of myocardial infarction, cardiac shock, stroke, stent thrombosis, or revascularization. We also set all-cause mortality as a secondary endpoint.Results: Out of the 547 patients, 29 patients had new-onset permanent LBBB, 51 patients had new-onset permanent RBBB, and 467 patients had no bundle-branch block (BBB). The occurrence of no BBB, new permanent LBBB, or RBBB was not associated with the severity of coronary artery lesions as evaluated by the GS. After follow-up at an average of 43.93 months, MACCEs occurred in 52 patients. Kaplan-Meier analysis showed that patients with new-onset RBBB were at greater risk for MACCEs compared to those with new onset LBBB (χ2 = 5.107, p = 0.021). Also, an independent correlation was found between new permanent RBBB and LBBB and MACCEs risk. The adjusted hazard ratios (HRs) were 6.862 [95% confidence interval (CI) of 3.764–12.510] for the new-onset permanent RBBB and 3.395 (95% CI of 1.280–9.005) for LBBB, compared to those with no BBB, respectively (both p < 0.05).Conclusion: New onset permanent RBBB in patients with new onset STEMI who underwent PCI may be correlated independently with increased risk of poor long-term prognosis.
Diabetic condition in animals might exert its influence on hematopoiesis via megakaryocytes-the newly identified modulator of hematopoietic stem cells in bone marrow.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.