ObjectiveTo explore the changes of focal adhesion kinase (FAK) in the fibrotic atrium of patients with valvular atrial fibrillation and explore its downstream signaling pathways.MethodsA total of 45 patients with mitral valve disease were included in this study and were divided into a valvular atrial fibrillation group (VAF, ≥6 months, 25 patients) and a sinus rhythm group (SR, 20 patients) based on having atrial fibrillation or not. The atrial appendage tissue was obtained during the operation , histopathological examination and Western blotting were performed. The degree of atrial fibrosis and changes in FAK and its downstream pathways in fibrotic myocardium were observed.ResultsThis study revealed a higher degree of atrial fibrosis in valvular atrial fibrillation and disordered cell arrangement. Expression of fibroblast differentiation marker alpha smooth muscle actin (α-SMA) was significantly increased in atrial fibrillation, and the expression of FAK and downstream AKT/S6K pathway proteins was up-regulated, while the other signal was observed, there was no significant change in ERK1/2 signaling pathway.ConclusionAtrial fibrosis in valvular atrial fibrillation is an important feature of atrial structural remodeling. We found overproduction of collagen fibers disrupted the continuity of atrial myocytes, leading to abnormal conduction and providing a matrix environment for the development of atrial fibrillation. The expression of focal adhesion kinase and downstream AKT/S6K signaling pathway in fibrotic myocardium may be involved in the process of atrial fibrosis, providing a basis for the study of its mechanism.
Objective To review the research progress of hair follicle stem cell(FSC) in wound healing and correlative signals. Methods The advances in the FSC location, characters, relations with wound repair and correlative singals were introduced based on the recent related literature. Results FSC played an important role in hair follicle cycle and wound healing. The correlative signals maybe Wnt, bone morphogenetic protein/transforming growth factor β, Norch, Shh and fibroblast growth factor. Conclusion The multipotency and plasticity of FSC offer a new way in regeneration medicine and the signals in cell proliferation and differentiation will be the new focus in future research.
ObjectiveTo investigate the expression pattern and significance of Sonic Hedgehog (Shh) signaling pathway by observing whether the Shh signaling pathway components express in the adult rat after spinal cord injury (SCI). MethodsSixty-four healthy male Sprague-Dawley rats were randomly divided into normal group (group A, 8 rats), sham group (group B, 8 rats), and SCI group (group C, 48 rats). In group A, the rats served as controls without any treatment; a decompressive laminectomy was performed on T7-9 levels without SCI in group B; and modified Allen's method was used to make SCI model in group C. Basso Beattie Bresnahan (BBB) scale was used to assess the hind limb motor function at 12 hours, 1 day, 3 days, 7 days, 14 days, and 21 days after SCI; the immunofluorescence staining, real-time PCR, and Western blot were performed to detect the mRNA and protein expression levels of Shh and Glioma-associated oncogene homolog-1 (Gli-1) in SCI zone. ResultsThe BBB score slowly increased with time in group C, but the scores at each time point in group C were significantly lower than those in group A and group B (P<0.05). The results of immunofluorescence staining showed that Shh and Gli-1 rapidly increased after SCI in astrocytes. Real-time PCR and Western blot showed that the relative expression levels of Shh and Gli-1 mRNA and protein were gradually increased in group C and reached a maximum at 7 days. In addition, the relative expression levels of Shh and Gli-1 mRNA and protein in group C were significantly higher than those in group A and group B (P<0.05). On the other hand, compared with group A, the expression of Gli-1 protein was reduced in the cytoplasm but increased in nucleus in group C. ConclusionAstrocytes synthesize and secrete Shh and Gli-1 signaling molecules after SCI, both Shh and Gli-1 significantly up-regulate and exhibit dynamic changes, which suggests Shh signaling pathway may be involved in nerve cell regeneration after SCI.
Familial exudative vitreoretinopathy (FEVR) is a serious hereditary retinal vascular disease. The clinical manifestations vary, and the severity of the patients' condition is different. In severe cases, it may lead to bilateral blindness. The pathogenic mechanism of FEVR is also complex. At present, more than ten classical and candidate pathogenic genes have been found: NDP, FZD4, LRP5, TSPAN12, CTNNB1, KIF11, ZNF408, RCBTB1, LRP6, CTNNA1, CTNND1, JAG1, ATOH7, DLG1, DOCK6, ARHGP31 and EVR3 region. These pathogenic genes are involved in Wnt/β-catenin signaling pathway, norrin/β-catenin pathway and Notch pathway. They regulate and affect the development of retinal blood vessels, hyaloid vascular system regression, endothelial cell connections, and blood retinal barrier homeostasis, ultimately leading to the occurrence and development of FEVR disease.
ObjectiveTo summarize the research progress of Hippo signaling pathway in triple negative breast cancer (TNBC). MethodLiteratures about studies the role of Hippo signaling pathway in cancer stem cells, epithelial-mesenchymal transformation, tumorigenesis and development, distant metastasis, treatment resistance, and treatment strategies were retrieved. ResultsIn TNBC, overexpression of Yes-associated protein and PDZ-binding motif could promote the development of tumor stem cells, induce epithelial-mesenchymal transformation of TNBC cells, and promote tumor development, distant metastasis, and chemotherapy resistance. ConclusionHippo/Yes-associated protein axis plays an important role in carcinogenesis and progression of TNBC, and targeting Hippo signaling pathway might be a potential therapeutic target for TNBC.
ObjectiveTo review the research progress of microenvironment for the treatment of peripheral nervous injuries. MethodsThe recent literature concerning the treatment mechanism of peripheral nervous injuries was extensively consulted, and the microenvironment response involved in the treatment of peripheral nervous injuries was reviewed. ResultsThe complex microenvironment for treatment of peripheral nervous injuries is dependent on nerve regeneration chamber, the formation of neurotrophic factors, inflammation response, regulation of hormones, signaling pathways, and related enzymes in regulation. In-depth study will help us have a clearer understanding on the distal and proximal neurons axons at the cellular and molecular levels after peripheral nervous injuries. ConclusionIn recent years, the researches of microenvironment for the treatment of peripheral nervous injuries have achieved obvious progress. With the current nanotechnology, materials science, genetic engineering, and stem cell transplantation technology, it will provide new ideas and corresponding basis for clinical treatment.
ObjectiveTo summarize the molecular mechanisms and clinical treatment of gastric cancer with liver metastasis (GCLM), in order to provide new ideas for future treatment. MethodThe literatures about mechanism and treatment strategy of GCLM in recent years were searched and reviewed. ResultsMost patients with gastric cancer were in advanced stage or had developed distant metastases when they were first diagnosed, among which liver was the common site of metastasis. The complex molecular mechanisms of GCLM had not been fully clarified. Molecular mechanisms at different levels, including non-coding RNA, circulating tumor cells, exosomes, tumor microenvironment and signaling pathways, were relatively independent and interacted with each other, providing potential biomarkers and therapeutic targets for GCLM. At present, the best treatment method for patients with GCLM was mainly divided into local and systemic treatment. The local treatment included surgical treatment, radiofrequency ablation and proton beam therapy, while the systemic treatment included systemic chemotherapy, targeted therapy and immunotherapy, among which the targeted therapy and immunotherapy were the focus of recent research. ConclusionsThe mechanism of GCLM is the result of the interaction between tumor cells and the microenvironment at the site of metastasis. Understanding them is of great significance to guide clinical treatment and prognosis. At present, there is no unified treatment standard for GCLM. To achieve the ideal treatment effect, we should not only rely on single therapy, but also adopt multi-disciplinary and individual therapy according to the specific disease status of patients and the nature of tumors.
Ferroptosis is a unique way of cell death discovered in recent years, which involves the lethal process of iron ion accumulation and lipid peroxidation, which is obviously different from the traditional cell death pathway such as apoptosis and necrosis. For a long time, tuberculosis has been a major infectious disease in the field of global public health, which brings a serious burden to the society because of its high morbidity and mortality. The emergence of drug resistance aggravates the difficulty of treating tuberculosis, and new treatment strategies and drug targets are urgently needed. Combined with the latest research progress at home and abroad, This article will discuss the molecular mechanism of ferroptosis and pulmonary tuberculosis and the relationship between signal pathways, biomarkers and related genes, in order to provide a new perspective for the diagnosis and treatment of pulmonary tuberculosis.
Lipopolysaccharide (LPS), the important component of the outer membrane of Gram-negative bacteria, contributes to the integrity of the outer membrane, and protects the cell against bactericidal agents. LPS, also called endotoxin synonymously, is well known as a potent inducer of the innate immune system that often causes septic shock in the intensive cares. Chemically, the amphiphilic LPS is made up of three parts, i.e. hydrophobic lipid A, hydrophilic core oligosaccharide chain, and hydrophilic O-antigenic polysaccharide side chain. Specially, the lipid A is known to be responsible for a variety of biological effects during Gram-negative sepsis. LPS can elicit a strong response from innate immune system and result in local or systemic adverse reactions. LPS can trigger massive inflammatory responses and may result in immunopathology, for which the molecular basis is mediated by the signal pathway of LPS. In recent years, a tremendous progress has been made in determining the associated proteins and receptors in the LPS signaling that leads to the disease. This review gives a summary of recent progresses of research on LPS and LPS receptors.