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Mitochondria are one of the most important organelles in cardiomyocytes. Mitochondrial homeostasis is necessary for the maintenance of normal heart function. Mitochondria perform four major biological processes in cardiomyocytes mitochondrial dynamics, metabolic regulation, Ca2+ handling, and redox generation. Additionally, the cardiovascular system is quite sensitive in responding to changes in mechanical stress from internal and external environments. Several mechanotransduction pathways are involved in regulating the physiological and pathophysiological status of cardiomyocytes. Typically, the extracellular matrix generates a stress-loading gradient, which can be sensed by sensors located in cellular membranes, including biophysical and biochemical sensors. In subsequent stages, stress stimulation would regulate the transcription of mitochondrial related genes through intracellular transduction pathways. Emerging evidence reveals that mechanotransduction pathways have greatly impacted the regulation of mitochondrial homeostasis. Excessive mechanical stress loading contributes to impairing mitochondrial function, leading to cardiac disorder. Therefore, the concept of restoring mitochondrial function by shutting down the excessive mechanotransduction pathways is a promising therapeutic strategy for cardiovascular diseases. Recently, viral and non-viral protocols have shown potentials in application of gene therapy. This review examines the biological process of mechanotransduction pathways in regulating mitochondrial function in response to mechanical stress during the development of cardiomyopathy and heart failure. We also summarize gene therapy delivery protocols to explore treatments based on mechanical stress-induced mitochondrial dysfunction, to provide new integrative insights into cardiovascular diseases.Sickle Cell Disease (SCD) is an autosomal recessive disorder resulting from a β-globin gene missense mutation and is among the most prevalent severe monogenic disorders worldwide. Haematopoietic stem cell transplantation remains the only curative option for the disease, as most management options focus solely on symptom control. Progress in prenatal diagnosis and fetal therapeutic intervention raises the possibility of in utero treatment. SCD can be diagnosed prenatally in high-risk patients using chorionic villus sampling. Among the possible prenatal treatments, in utero stem cell transplantation (IUSCT) shows the most promise. IUSCT is a non-myeloablative, non-immunosuppressive alternative conferring various unique advantages and may also offer safer postnatal management. Fetal immunologic immaturity could allow engraftment of allogeneic cells before fetal immune system maturation, donor-specific tolerance and lifelong chimerism. In this review, we will discuss SCD, screening and current treatments. We will present the therapeutic rationale for IUSCT, examine the early experimental work and initial human experience, as well as consider primary barriers of clinically implementing IUSCT and the promising approaches to address them.Colorectal cancer (CRC) is the third leading cause of cancer-related deaths globally and is biologically and clinically heterogeneous. Due to lack of gene expression signatures for risk and prognosis stratification of CRC, identifying novel molecular biomarkers and therapeutic targets may potentially improve CRC prognosis and treatment. RNF180 has been shown to play key contributions to the development of several types of cancers. In the current study, we investigate its role in CRC. In this study, we show that RNF180 expression was significantly downregulated in human CRC tumors and cell lines. Overexpression of RNF180 in CRC cells markedly inhibited cell viability and induced cell apoptosis, while depletion of RNF180 dramatically enhanced cell survival. Moreover, WISP1 was found to be the critical downstream molecule that mediated the tumor suppressive effects of RNF180. Mechanistically, RNF180 ubiquitinated WISP1, resulting in WISP1 downregulation and ultimately leading to suppression of CRC tumor growth in patient-derived xenograft (PDX) mouse models. Last, 5-FU and RNF180 had synergetic effect on the apoptosis induction and tumor growth inhibition. Our findings revealed a crucial role of RNF180 in suppressing tumor growth by ubiquitinating WISP1 in CRC.Some essential hypertension (EH) patients show maternal inheritance, which is the mode of mitochondrial DNA inheritance. This study examines the mechanisms by which mitochondrial mutations cause EH characterized by maternal inheritance. The study enrolled 115 volunteers, who were divided into maternally inherited EH (group A, n = 17), non-maternally inherited EH (group B, n = 65), and normal control (group C, n = 33) groups. A mitochondrial tRNA (15910 C>T) gene mutation was significantly correlated with EH and may play an important role in the pathogenesis of maternally inherited EH. Examining two families carrying the mitochondrial tRNA 15910 C>T mutation, which disrupted base pairing and may affect the stability and function of mitochondrial tRNAThr, we find that the overall incidence of EH was 59.3% in the maternal family members and 90% in males, significantly higher than in the general population in China (23.2%), and that the EH began at a younger age in those carrying mitochondrial tRNA 15910 C>T. To reveal the mechanism through which mitochondrial tRNA 15910 C>T causes maternally inherited EH, we cultured human peripheral blood mononuclear cells from family A2 in vitro. We find that cells carrying mitochondrial tRNA 15910 C>T were more viable and proliferative, and the increased ATP production resulted in raised intracellular reactive oxygen species (ROS). Moreover, the mitochondrial dysfunction resulted in reduced APN levels, causing hypoadiponectinemia, which promoted cell proliferation, and produced more ROS. This vicious cycle promoted the occurrence of EH with maternally inherited mitochondrial tRNA 15910 C>T. SAR7334 research buy The mitochondrial tRNA 15910 C>T mutation may induce hypertension by changing the APN, AdipoR1, PGC-1α, and ERRα signaling pathways to elevate blood pressure. We discover a new mitochondrial mutation (tRNA 15910 C>T) related to EH, reveal part of the mechanism by which mitochondrial mutations lead to the occurrence and development of maternally inherited EH, and discuss the role of APN in it.
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