Autophagy and myocardial ischemia/reperfusion injury

Autophagy is a lysosome-dependent degradative pathway which is characterized by cytoplasmic vacuolization. However, it is not just a simple degradative pathway. Research shows that autophagy is related to many diseases, such as neurodegenerative disease, malignant tumor, ageing, pathogenic microorganism infection, myocardial ischemia/reperfusion injury and so on. Autophagy exactly exists in myocardial ischemia/reperfusion injury, and it becomes a new research hotspot. This review will focus on the occurrence and development of autophagy and its role, signal transduction and research status in myocardial ischemia/reperfusion injury.     

Present investigation of PTEN gene in cardiovascular system

PTEN gene, identified in 1997 and named after the separation, was a new candidate tumor suppressor gene. The mutations of PTEN gene, loss of heterozygosity in human tumors are prevalent, such as malignant glioma, endometrial cancer, prostate cancer, breast cancer, etc. The mutation frequency of PTEN is equivalent to p53. As an important functional element and a tumor suppressor gene, most scholars agree that PTEN gene is as important as p53. At present, studies on the PTEN gene mainly concentrated in the tumor area, its functions in the cardiovascular system are few reports. This article reviews the investigation of PTEN gene in the cardiovascular system.     

Molecular mechanisms of deubiquitinase OTUD7B in regulating tumor microenvironment and progression

Ubiquitination and deubiquitination are important mechanisms for regulating cell signal transduction. They regulate target proteins precisely and participate in physiological and pathological processes such as growth, development, immune response and cancer. OTUD7B (OTU domain-containing 7B) is a deubiquitinase that hydrolyzes K11-, K48- and K63-linked polyubiquitin chains, regulates intracellular signal transduction and mediates cell survival and proliferation. The abnormal expression of OTUD7B in various malignant tumors affects tumor progression and immune microenvironment. Here, we reviewed OTUD7B-mediated cellular signal transduction and its role in malignant tumors, in order to provide clues for the discovery of new targets of anti-cancer therapy targeting ubiquitin system.     

Effect of phosphatidylinositol 3-kinase in angiogenesis-related diseases

Angiogenesis is involved in the pathological processes such as wound healing, atherosclerosis, rheumatoid arthritis and tumor, in which the pathogenesis and development are closely related to the new blood vessel formation. Phosphatidylinositol 3-kinase (PI3K), one of the important intracellular signaling proteins, mediates many signal transductions in cell migration, proliferation and angiogenesis. The activity of PI3K and its signaling pathway play a unique role in atherogenesis, unstability of atherosclerotic plaque, tumor metastasis and recurrence, etc. This review summarizes the effect of PI3K in angiogenesis-related diseases.     

p300/p53/Smad3 pathway involved in aging-related atrial fibrosis in human atrial fibroblasts

AIM To investigate the role of p300 in aging-related atrial fibrosis in human atrial fibroblasts （HAFs） and its potential mechanism. METHODS HAFs were obtained from human left atrial tissue, and the senescence model was established by cell passage. Senescence-associated β-galactosidase （SA-β-Gal） staining was used to detect the cell senescence, and Western blot was used to determine the protein levels of p300, p53, Smad3 and other senescence and fibrosis associated proteins in HAFs. RESULTS Compared to passage 3 HAFs, the proportion of senescent cells, and the protein levels of p300, p53, p-Smad3 and other senescence and fibrosis associated proteins were increased in HAFs at passage 7 and 11 （P<0.05）. After treated with curcumin （a p300 inhibitor） or transfection with p300 small-hairpin （sh） RNA plasmid, the protein levels of p300, and the senescence and fibrosis associated proteins were decreased in HAFs at passage 7（P<0.05）. Up-regulation of p300 by transfection with p300 over-expression plasmid increased the protein levels of p53, Smad3 and MMP-2 in HAFs at passage 3 （P<0.05）. CONCLUSION p300/p53/Smad3 signaling pathway plays an important role in aging-related atrial fibrosis in HAFs.     

Regulatory pathway of hypoxia-inducible factor and its role in intestinal diseases

Intestinal tract is the largest organ of the human body. It plays an important role in the absorption of nutrients and the resistance to pathogens. At the same time, it is also regulated by oxygen supply. Hypoxia-inducible factor (HIF) is a key factor in the regulation of hypoxia and plays a key role in maintaining the homeostasis of the intestinal environment. In the development of inflammatory bowel disease, intestinal tumor, ischemia-perfusion injury and intestinal flora imbalance, HIF responds to inflammation and hypoxia, and causes an important adaptive response in intestinal mucosa, thus maintaining the function of the intestinal epithelium or promoting the development of intestinal tumors. In this review, the recent advances in HIF structure, function and regulatory pathways, and its role in intestinal diseases are reviewed.     

Progress of ELMO family on malignant tumor invasion and metastasis

It is one of the main characters of malignant tumors that malignant tumor cells invade surrounding tissues and metastasize to distant tissues. Multiple factors are involved in this complicated dynamic process. Metastasis is the major factor influencing recurrence and prognosis. Therefore, it is important to explore the mechanism of invasion and metastasis for reducing recurrence rate and mortality of malignant tumors. Engulfment and cell mobility (ELMO) family is one kind of conserved protein in evolutional process. It includes 3 members, ELMO1, ELMO2 and ELMO3. The members of ELMO family play an important role in cell phagocytosis and cell migration, and they also have close correlation with malignant tumor cell invasion and metastasis. In this paper, we review the progress of the relationship between ELMO family and malignant tumor invasion and metastasis.     

Roles of SARS-CoV-2 receptor ACE2 in various diseases

It is well know that severe acute respiratory syndrome coronavirus 2 （SARS-CoV-2） can enter host cells through angiotensin-converting enzyme 2 （ACE2）, which is a key step in the development of coronavirus disease 2019 （COVID-19）. At the same time, ACE2 is expressed in a variety of tissues and regulates many biological functions, including inflammation, cell proliferation and oxidative stress, as a key negative regulator of the renin-angiotensin system. It plays an important role in the changes of physiological functions and pathological diseases of multiple systems and organs. Therefore, in addition to COVID-2019, ACE2 is also a potential therapeutic target for the diseases such as acute lung injury, cardiovascular diseases, cancer, and kidney diseases. This article reviews the mechanism of ACE2 in the above diseases and new strategies for therapeutic application.     

Role of insulin resistance in neurodegenerative diseases

Insulin resistance is a condition in which the cells fail to respond to the normal actions of insulin, acting as decreased glucose utilization, abnormal glucose tolerance and compensatory increased insulin concentration in the serum. Altered insulin-related indicator has been detected in neurodegenerative diseases. Recent studies indicate that insulin resistance is involved in the occurrence and development of neurodegenerative diseases, including Alzheimers disease, Parkinsons disease, Huntingtons disease, etc. This review summarizes the relationship between insulin resistance and neurodegenerative diseases.     

Integrins and cardiovascular diseases

The adhesion of cells to each other and to the proteins of the extracellular matrix provides a stable environment for cell growth, differentiation and migration. This is a prerequisite for the normal function of the cardiovascular system. Thus the abnormal adhesion function may play a key role in the pathogenesis and development of cardiovascular diseases. To date, there are six main groups of adhesion molecule, and integrins family are the largest and most broadly distributed of the families of cellular adhesion receptors. They have an important role in several aspects of cardiovascular diseases and that its regulated inhibition leads to a reduction in incidence andmortality due to these disorders. This review focuses upon the structure, mechanism and their roles in cardiovascular diseases which maybe facilitate the development of novel therapies.     

Effects of miR-337 targeting p53 expression on autophagy and migration ability of colon cancer cells

AIM: To investigate the effect of microRNA-337 (miR-337) on the autophagy and migration ability of colon cancer cells, and to explore its possible mechanism involving targeting p53 expression. METHODS: The me-thod of immunohistochemistry was used to detect the protein expression of beclin-1, LC3B and p53 in colon cancer tissues. The correlations between the protein expression of beclin-1/LC3B and clinicopathological features, and the correlations between the protein expression of p53 and beclin-1/LC3B were analyzed. After knock-down of p53 expression by small interfering RNA, the formation of autophagiosomes was observed under electron microscope in colon cancer cell line HCT116, and the protein expression of beclin-1 and LC3B was determined by Western blot. The miRNAs targeting p53 were predicted and screened by bioinformatics, and their expression in HCT116 cells was verified by RT-qPCR. Luciferase reporter assay was used to detect the regulatory effect of miR-337 on p53 gene. The protein expression of p53, beclin-1 and LC3B was determined by Western blot, and the migration ability of HCT116 cells after miR-337 over-expression was detected by Transwell assay. RESULTS: The protein expression of beclin-1 and LC3B in the colon cancer tissues was decreased, which was significantly related to the occurrence, development, invasion and metastasis of colon cancer. The expression of p53 was increased in the colon cancer tissues, which was negatively correlated with the protein expression of beclin-1 and LC3B. Knock-down of p53 gene expression increased the protein expression of beclin-1 and LC3B (P<0.05). Over-expression of miR-337 down-regulated the expression of p53, up-regulated the protein expression of beclin-1 and LC3B, and decreased the migration ability of HCT116 cells (P<0.05). CONCLUSION: miR-337 promotes autophagy and inhibits migration ability of colon cancer cells, and the mechanism may be related to targeted inhibition of p53 expression.     

Lentivirus-mediated shRNA interference of ghrelin receptor blocks growth of colorectal cancer cells

AIM: To investigate the therapeutic effects of lentivirus-mediated shRNA targeting growth hormone secretagogue receptor 1a(GHSR1a) on colorectal cancer cell line SW480 both in vitro and in vivo. METHODS: Human GHSR1a sequence was used for the design of shRNA targeting GHSR1a, which was introduced to lentivirus, followed by transfection into SW480 cells. CCK-8 assay was performed to detect cell viability. The mRNA expression of GHSR1a and PTEN in colorectal cancer cells was detected by RT-PCR. The protein levels of GHSR1a, ghrelin, PTEN, p-AKT and p53 were determined by Western blot. Stable GHSR1a silencing in SW480 xenografts in nude mice was established. After the mice were sacrificed and weighted, immunohistochemistry was used to detect the positive expression of Ki-67 and PTEN in the tumors. RESULTS: GHSR1a was over-expressed in the malignant cells in comparison with the normal cells in vitro. The tumor specific lentivirus-mediated shRNA targeting GHSR1a gene and GHSR1a knockdown SW480 cells were successfully constructed. After transfection with GHSR1a shRNA, the expression of GHSR1a at mRNA and protein levels was markedly inhibited in the SW480 cells. Furthermore, GHSR1a silencing by specific shRNA showed increased PTEN, inhibition of AKT phosphorylation and promotion of p53 release in the SW480 cells. In vivo results demonstrated that down-re-gulation of GHSR1a in the SW480 cells significantly decreased the expression of Ki-67 and increased the expression of PTEN in the tumor tissues, leading to a marked reduction in tumor weight in comparison to blank control or negative control tumors. CONCLUSION: Down-regulation of GHSR1a by shRNA technique inhibits the growth of colorectal cancer cell line and xenograft tumor through activation of the PTEN/PI3K/AKT signaling pathways.     

P53 overexpression in different subcellular location in non small cell lung cancer

AIM: Nuclear P53 localization was considered to be proof of mutation, cytoplasmic staining has also been signalled. In this study, special attention has paid to protein subcelluler localization. A different functional meaning may attributed to tumor biological characteristic and evolution. METHODS: Immunohistochemical approach and flow cytometry were used to explored the relationship between P53 overexpression pattern (nuclear and cytoplas- mic) and G₁/S checkpoint function of P53 protein in cell cycle. RESULTS: Two patterns of P53 overexpression are related to disease stage significantly. S - phase fraction (SPF) was higher and G₀-G₁ phase fraction was lower in P53 nuclear pattern than cytoplasmic (SPF, 42.42± 5.45/14. 12± 442, G₀-G₁: 53.04 ± 6.14／75.56 ± 4.46, respectively P < 0.05). No difference was found in G₂ - M phase fraction and DNA index between two patterns. CONCLUSION: Most of the cells showing cytoplasmic P53 overexpression pattern are properly arrested in G/S checking point, which may represent an early tumor cell population with low grade of neoplastic development. In contrast, inactivated product detectable at nuclear level possible carry a mutated P53 associated with tumor progression. The mechanism of P53 cytoplasmic location is not clear.