Left ventricular noncompaction(LVNC) is a relatively rare cardiomyopathy due to the cessa tion of endocardial and myocardial cells in the early embryo development.The disease mainly is involved in the left ventricle.LVNC is sporadic or familial genetic disease,which has obvious genetic heterogeneity.It is X linkage and autosomal dominant inheritance.The genetic characteristics of LVNC are not single inheritance,and its pathogenic gene and mutation site are diverse.It has been shown that LVNC has a close correlation with multiple gene mutations,and it is also overlap with the genes that caused other cardiomyopathy.In this paper,we will review the research progress of LVNC and related gene mutations.

Animals ; B7-H1 Antigen ; immunology ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; immunology ; Humans ; Interferons ; immunology ; Mice ; Neoplasm Proteins ; immunology ; Neoplasms ; immunology ; Up-Regulation ; immunology

ObjectiveTo observe the mechanism of Jiawei Guizhi Fuling decoction （JGFD） in alleviating sciatic nerve injury in painful diabetic peripheral neuropathy （PDPN） rats by regulating mitophagy through the PTEN-induced putative kinase 1 （PINK1）/Parkin signaling pathway. MethodThe PDPN model was established by intraperitoneal injection of streptozotocin （STZ）. After modeling， the rats were randomly divided into JGFD high， medium， and low dose groups （JGFD-H， JGFD-M， JGFD-L； 39.6， 19.8， 9.9 g·kg^-1·d^-1， respectively）， a positive drug group （lipoic acid capsules， LA； 50 mg·kg^-1·d^-1）， and a model group （PDPN）. A blank control group （CON） was established. Drug intervention was administered continuously for 8 weeks after modeling. Measurements included body weight and fasting blood glucose of PDPN rats at weeks 0， 2， 4， and 8， mechanical pain threshold and thermal pain threshold at weeks 0 and 8， and motor nerve conduction velocity at week 8. Hematoxylin-eosin （HE） staining was used to observe the morphology of sciatic nerve tissue. The ultrastructure of mitochondria and autophagosomes was observed by transmission electron microscopy. Western blot was performed to detect the protein expression levels of PINK1， Parkin， p62， Beclin-1， and LC3 in sciatic nerve tissue. Additionally， real-time quantitative PCR （Real-time PCR） was performed to detect the mRNA expression levels of PINK1， Parkin， p62， Beclin-1， and LC3 in sciatic nerve tissue. ResultCompared with the CON group， the PDPN group showed a significant decrease in body weight at all time points， a significant increase in fasting blood glucose， significantly shortened mechanical pain and thermal pain thresholds， and significantly reduced motor nerve conduction velocity. The protein and mRNA expression of PINK1， Parkin， Beclin-1， and microtubule-associated protein light chain 3（LC3） in sciatic nerve tissue was significantly reduced， while p62 protein and mRNA expression was significantly increased （P<0.01）. Pathological changes included edema of sciatic nerve fibers， segmental demyelination， loose and disordered arrangement of the myelin sheath layers， significant swelling of mitochondria， reduced electron density， disappearance of cristae， and absence of typical autophagosome and autolysosome structures. Compared with the PDPN group， each JGFD dose group showed a significant increase in body weight and a significant reduction in fasting blood glucose （P<0.05， P<0.01）. The mechanical pain threshold and thermal pain threshold were significantly prolonged， and motor nerve conduction velocity was significantly increased across all JGFD and LA groups. The expression levels of PINK1， Parkin， Beclin-1， and LC3 proteins and mRNA in sciatic nerve tissue were significantly increased， while p62 protein and mRNA expression levels were significantly decreased （P<0.05， P<0.01）. Pathological damage to the sciatic nerve was alleviated to varying degrees， with a relatively intact myelin sheath morphology and intact or slightly edematous outer mitochondrial membrane. Autophagolysosome structures were observed in the JGFD-M and JGFD-H groups. Compared with the LA group， the JGFD-H group showed a significant increase in body weight， a significant reduction in fasting blood glucose， a significant increase in motor nerve conduction velocity， a significant increase in PINK1 protein expression and PINK1， Parkin， and Beclin-1 mRNA expression in sciatic nerve tissue， and a significant decrease in p62 mRNA expression （P<0.05， P<0.01）. ConclusionJGFD may alleviate sciatic nerve injury in PDPN rats by activating mitophagy through the regulation of the PINK1/Parkin signaling pathway.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is the fourth-leading cause of cancer-related deaths worldwide. HCC is refractory to many standard cancer treatments and the prognosis is often poor, highlighting a pressing need to identify biomarkers of aggressiveness and potential targets for future treatments. Kinesin family member 2C (KIF2C) is reported to be highly expressed in several human tumors. Nevertheless, the molecular mechanisms underlying the role of KIF2C in tumor development and progression have not been investigated. In this study, we found that KIF2C expression was significantly upregulated in HCC, and that KIF2C up-regulation was associated with a poor prognosis. Utilizing both gain and loss of function assays, we showed that KIF2C promoted HCC cell proliferation, migration, invasion, and metastasis both in vitro and in vivo. Mechanistically, we identified TBC1D7 as a binding partner of KIF2C, and this interaction disrupts the formation of the TSC complex, resulting in the enhancement of mammalian target of rapamycin complex1 (mTORC1) signal transduction. Additionally, we found that KIF2C is a direct target of the Wnt/β-catenin pathway, and acts as a key factor in mediating the crosstalk between Wnt/β-catenin and mTORC1 signaling. Thus, the results of our study establish a link between Wnt/β-catenin and mTORC1 signaling, which highlights the potential of KIF2C as a therapeutic target for the treatment of HCC.
Adult ; Aged ; Animals ; Carcinoma, Hepatocellular/pathology* ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Epithelial-Mesenchymal Transition/genetics* ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism* ; Kinesins/metabolism* ; Liver Neoplasms/pathology* ; Male ; Mice ; Mice, Inbred BALB C ; Middle Aged ; Neoplasm Staging ; Prognosis ; Protein Binding ; RNA, Small Interfering/metabolism* ; Survival Analysis ; Tumor Burden ; Wnt Signaling Pathway ; Xenograft Model Antitumor Assays ; beta Catenin/metabolism*