Advances in function of circular RNA and regulation of atherosclerosis development

Atherosclerosis is one of the cardiovascular diseases that seriously endanger human health. The pathogenesis of atherosclerosis is very complicated and related to a variety of risk factors. In recent years, many studies have found that circular RNAs play an important regulatory role in the occurrence and development of atherosclerosis by inducing proliferation, differentiation, migration and apoptosis of vascular smooth muscle cells, endothelial cells and macrophages. This article reviews the basic functions of circular RNAs and its recent research on the regulation of atherosclerosis.     

Effect of midkine,a newly heparin-binding cytokine,on cardiovascular functions

Midkine (MK), a newly discovered heparin-binding growth factor, promotes growth, survival, and migration in various cells. Meanwhile, MK stimulates statistically significant forms in new arterioles and capillaries, causes vascular remodeling, prevents ischemia myocardial cells from injury via inhibiting apoptosis. MK also regulates the level of blood-fat. In general, MK plays key roles in cardiovascular diseases.     

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.     

Investigation progress of CaSR in cardiovascular system

Calcium sensing receptors (CaSR) is a member of super-family of G-protein coupling receptors. This review first introduced the concept, construction features, distribution, functions, decision methods, moderators, genetic locus of CaSR and its relationship with some diseases concisely. Then this article described the investigation progress of CaSR in cardiovascular system intensively, including the expression pattern, role and signal pathways of CaSR in rat myocardium in normal, ischemia-reperfusion injury, apoptosis and cardiac hypertrophy; the role and mechanism of CaSR in calcium homostasis regulation of rat myocardium, endoplasmic reticulum (ER) stress and cardiac ischemic preconditioning and postconditioning. The metabolism rule, physiological significance and pathological action of polyamine in cardiac cells; the increase of CaSR expression in cardiac tissue of artherosclerosic rat and its effect on sensitivity to acute myocardial infarction are also discussed. In the end, the research perspective of CaSR in cardiovascular system was anticipated.     

Relationship between microRNAs and autophagy in Schwann cells during peripheral nerve regeneration and repair

The survival, proliferation and differentiation of Schwann cells are the decisive factors of peripheral nerve regeneration. Autophagy is an important mechanism to regulate homeostasis and make Schwann cells pass the stress period, thus providing protection for the survival of Schwann cells and becoming a key factor on nerve regeneration. Recent studies indicate that a number of microRNAs participate in the activity of Schwann cells and play an important regulatory role in the process of nerve injury repair. In our studies, we found that microRNAs played an important regulatory role in autophagy at the early stage of nerve injury. Therefore, the relationship between microRNAs and autophagy in Schwann cells during the regeneration and repair of peripheral nerve injury is described in this paper.     

Pivotal role of microRNAs in cardiac development and heart diseases

MicroRNAs (miRNAs) are non-coding small RNAs, which bind to the 3'-UTR of target mRNAs and negatively regulate the gene expression. Accumulating evidence demonstrates that miRNAs are involved in many biological processes such as embryo development, cell proliferation, differentiation, apoptosis and tumorigenesis. Heart development and heart diseases are complex processes controlled by various signaling pathways. Recent researches indicate the importance of miRNAs in the process of cardiac development and heart diseases. In this review, the role of miRNAs in cardiac development and the pathogenesis of heart diseases are overviewed. The insight into the regulating miRNAs will significantly expand the cardiovascular therapeutic strategies beyond classical pharmacology.     

Progress of STIM1, a dynamic calcium signal transducer, #br# in cardiovascular diseases

Stromal interaction molecule 1 (STIM1) is a transmembrane protein of the endoplasmic reticulum (ER), a Ca²⁺ transducer in ER that activates the store-operated calcium channel. Through Orai1 protein, STIM1 adjusts the intracellular and extracellular calcium concentration. This way is called a store-operated Ca²⁺ entry. STIM1 plays a key role in phenotypic transformation of vascular smooth muscle cells, proliferation of endothelial cells, myocardial hypertrophy and myocardial fibrosis to regulate lots of cardiovascular diseases, such as atherosclerosis, congestive heart failure and systemic hypertension. STIM1 is closely related to cardiovascular diseases through calcium signal. The research progress of STIM1 in cardiovascular diseases is mainly discussed in this article.     

Changes of miR-155-5p in serum of cervical cancer patients and effects of miR-155-5p on cervical cancer cells

AIM:To detect the serum level of miR-155-5p in the patients with different cervical diseases, and to analyze its effects on the proliferation, cell cycle and apoptosis of cervical cancer cells. METHODS:SYBR Green I real-time quantitative PCR was used to detect the level of miR-155-5p in the serum of the patients with different cervical diseases. miR-155-5p mimic or inhibitor was used to increase or decrease the expression of miR-155-5p in cervical cancer cells. The proliferation, cell cycle and apoptosis were measured by CCK-8 assay and flow cytometry. RESULTS:The serum level of miR-155-5p in cervical cancer group was higher than that in cervicitis group and healthy group. No statistical difference of the serum miR-155-5p level between cervical intraepithelial neoplasia group and cervical cancer group was observed. Compared with blank group, liposome group and negative control group, the proportion of S-phase cells increased and apoptotic cells decreased in SiHa cells transfected with 100 nmol/L and 200 nmol/L miR-155-5p mimic. The proportion of G2/M-phase cells increased significantly in SiHa cells transfected with 100 nmol/L and 200 nmol/L miR-155-5p inhibitor. CONCLUSION: Compared with healthy controls, the serum level of miR-155-5p in the cervical cancer patients increases, and may act as a novel tumor molecular marker for diagnosis of cervical cancer. miR-155-5p has no significant effect on the proliferation, cell cycle and apoptosis of HeLa cell. miR-155-5p may promote SiHa cells to enter S phase and inhibit the apoptosis of SiHa cells.     

Influence of Sini decoction on the proliferation and apoptosis of artery smooth muscle cells after balloon injury

AIM: To investigate the influence of Sini decoction (SND) on the proliferation and apoptosis of rabbit abdominal aorta smooth muscle cells after ballon injury and discuss the effect of vascular smooth muscle cell's (VSMCs) proliferation and apoptosis in post-percutaneous coronary intervention (PCI) restenosis (RS) and the feasibility of SND preventing post-PCI RS. METHODS: The animal model of rabbit abdominal aorta ballon injury was set up and the therapertic group was treated with SND. The shape of proliferative and apoptotic cell were investigated by electron microscope. Immunohistochemistry staining was performed using α-actin,PCNA and Cyclin E monoclonal antibodies. In situ Cell Death Detection Kit was used to identify apoptotic cells. Abdomial aorta angiography was operated in the 84th day subgroup and the stenosis degree was evalued by quantitative angiographic analysis. RESULTS: As compared with the control group, the therapeutic group displayed a lower proliferative percentage and a higher apoptosic percentage (P<0.05). Moreover, the apoptosic peek time was on the 14th day after operation,which was longer than the control group. CONCLUSION: SND effectly inhibited the proliferation of VSMCs and iuduced apoptosis in VSMCs.     

Long non-coding RNA HOTAIR modulates proliferation and apoptosis of acute lymphoblastic leukemia cells

AIM: To explore the influence of long non-coding RNA HOTAIR on the proliferation and apoptosis of acute lymphoblastic leukemia cells via the regulation of glucocorticoid receptor (GR).METHODS: The expression le-vels of HOTAIR and GR mRNA in human bone marrow stromal cell line HS-5 and human acute lymphoblastic leukemia cell lines MOLT-4, CCRF-CEM and CEM-C1 were examined by RT-qPCR. HOTAIR was knocked down by siRNA in acute lymphoblastic leukemia cells. CCK-8 assay was used to assess the cell viability, and the effect of si-HOTAIR on the proli-feration of CEM-C1 cells was evaluated by BrdU method. The effect of si-HOTAIR on apoptosis of CEM-C1 cells was examined by Hoechst 33342 staining and Caspase-Glo^® 3/7 assay. Western blot was utilized to examine the protein level of GR.RESULTS: The expression level of HOTAIR in acute lymphoblastic leukemia cells was significantly increased as compared with normal human bone marrow stromal cells (P<0.01). The viability and proliferation of acute lymphoblastic cells was inhibited, the apoptosis was induced, and the anti-proliferation effect of dexamethasone on CEM-C1 cells was enhanced after knockdown of HOTAIR expression (P<0.01). The expression of GR was up-regulated at both mRNA and protein levels (P<0.01).CONCLUSION: Long non-coding RNA HOTAIR may modulate the viability, proliferation and apoptosis of acute lymphoblastic leukemia cells via a GR regulatory way.     

Roles of CFTR Cl- channels in hydrogen sulfide-induced cardioprotection and cell proliferation in H9c2 cells

AIM: To explore the roles of cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels in hydrogen sulfide (H2S)-induced cardioprotection and cell proliferation in H9c2 cells. METHODS: Cobalt chloride (CoCl2) was used to set up the chemical hypoxia-induced injury model in H9c2 cells. Myocardial cell viability was detected by the CCK-8 assay kit. Apoptotic changes in H9c2 cells were observed by using Hoechst 33342 staining and photofluorography. RESULTS: At the concentrations from 400 to 2 000 μmol/L, CoCl2 dose-dependently inhibited cell viability in H9c2 cells. CoCl2 at concentration of 600 μmol/L significantly induced H9c2 cell apoptosis. Sodium hydrosulfide (NaHS) at concentrations from 100 to 400 μmol/L dose-dependently enhanced proliferation in H9c2 cells. NaHS protected H9c2 cells against CoCl2-induced injury, including an increase in cell viability and a decrease in percentage of apoptosis. 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB, 100 μmol/L), an inhibitor of CFTR Cl- channels alone did not damaged H9c2 cells, but considerably blocked the inhibitory effect of NaHS on CoCl2 cytotoxicity. However, NPPB did not antagonize the NaHS-induced antiapoptotic effect and cell proliferation in H9c2 cells. CONCLUSION: CFTR Cl- channels may be involved in the inhibitory effect of H2S on CoCl2-induced cytotoxicity in H9c2 cells.     

Effect of activated protein C on apoptosis in human umbilical vein endothelial cells induced by lipopolysaccharide

AIM:To study the effect of activated protein C (APC) at different concentrations on apoptosis of human umbilical vein endothelial cells (HUVECs) induced by lipopolysaccharide (LPS).METHODS:The HUVECs were induced by LPS (1.0 mg/L) as apoptotic model that was administered by different concentration of APC (10 μg/L or 50 μg/L). Meanwhile, the control group and induced apoptosis group induced by LPS (1.0 mg/L) stimulation were also set up. The changes of cellular ultrastructures were observed under electron microscope. The DNA ladder and TUNEL fluorescent staining were measured in cells. Annexin-Ⅴ/PI double staining was used to measure the cell apoptosis rate by flow cytometry. Cell survival rate was measured by MTT assay. The proliferating cell nuclear antigen (PCNA) expression levels in cells were also measured by Western blotting to reflect the proliferation of the cells.RESULTS:There were significant apoptotic changes in the cells induced by LPS, but the apoptotic changes were reduced and apoptosis rates were decreased in the cells treated with APC. Meanwhile, cell survival rate and the protein levels of PCNA were increased after APC treatment, particularly at the concentration of 50 μg/L, which showed difference when compared with those induced apoptosis group by LPS (P<0.05).CONCLUSION:APC can inhibit HUVECs apoptosis induced by LPS and promote cell proliferation, thus protect the cells from injury.     

Tumor necrosis factor-related apoptosis-inducing ligand participates in injury of vascular endothelial cells induced by rapamycin in vitro

AIM: To investigate the effects of rapamycin on apoptosis, proliferation, migration ability and tumor related apoptosis inducing ligand(TRAIL) in cultured human umbilical vein endothelial cells(HUVECs). METHODS: Cultured HUVECs were treated with rapamycin at the concentrations of 0, 1, 10 and 100 μg/L for 24 h. The cell proliferation was measured by CCK-8 method. The cell migration ability was detected by Transwell chambers and wound healing test. The apoptotic index of HUVECs was quantitatively determined by measuring the activation of caspase-3. The morphological changes of the apoptotic cells were observed by DAPI staining. The expression of TRAIL was detected by Western blotting. RESULTS: A 24 h-incubation with rapamycin(1-100 μg/L) caused significant cell loss associated with the increase in apoptosis, as quantified by the determination of caspase-3 activity(P<0.01) in HUVECs. Obvious apoptotic morphology was observed by DAPI staining in HUVECs incubated with rapamycin. Rapamycin at the concentrations of 1-100 μg/L also impaired the migration ability of HUVECs(P<0.01). In addition, rapamycin(10-100 μg/L) inhibited the proliferation of HUVECs, whereas rapamycin at 1 μg/L had no such effect(P<0.01). Rapamycin(10-100 μg/L) also induced TRAIL expression in a dose-dependent manner(P<0.01). CONCLUSION: Rapamycin induces apoptosis, and inhibits the proliferation and migration of HUVECs. The up-regulation of TRAIL might be related to the injury of vascular endothelial cells caused by rapamycin.     

Formation and activity of lymphocyte-derived microparticles

Lymphocyte-derived microparticles (LMPs) are small membrane vesicles that are released upon activation or during apoptosis from lymphocytes.The LMPs were detected at elevated levels in the patients with inflammatory diseases, cardiovascular diseases or diabetes. In addition, LMPs are important mediators of transferring biological information and switching on the biological effects through their interaction with the target cells. Moreover, LMPs play completely distinct roles in different physiological and pathological conditions. This article describes the possible mechanism involved in the formation, composition, key biological activities and the relationship with diseases.     

Advance in biological properties of IL-38 and its role in pulmonary diseases

Interleukin-38 （IL-38） is the most recently discovered cytokine of the IL-1 family and is an IL-36 receptor inhibitor. IL-38 is mainly expressed in human immune organs and associated with a variety of diseases. In the process of apoptosis and necrosis caused by injury or inflammation， researchers have studied quiet a lot about the kinase， cleavage sites， activity regulatory mechanism， signal transduction ligand， transduction mode and potential receptors of IL-38， but many mechanisms are still unknown. This article reviews the role of IL-38 in the pathogenesis and progression of lung tumors， asthma and interstitial lung disease. We also discussed the role of IL-38 in the treatment of these diseases， the possible relationship between IL-38 and tuberculosis， and the direction of future studies on the mechanism of IL-38 action.     

Mesenteric lymph drainage alleviates spleen injury in hemorrhagic shock rats

AIM：To observe the effects of post-shock mesenteric lymph (PSML) drainage on histopathology, apoptosis, cell cycle and proliferation of the spleen in rats with hemorrhagic shock. METHODS：Eighteen Wistar rats were randomly divided into sham, shock and shock+drainage groups (n=6 in each group). The hemorrhagic shock model was established in the shock and shock+drainage groups. Fluid resuscitation for 30 min was performed 1.5 h after hypotension, and PSML was drained in the rats in shock+drainage group from 1 h after hypotension to 3 h after resuscitation finished. The fixed spleen tissue was harvested from each rat for histological observation with HE staining. The apoptosis of splenocytes was observed by Hoechst 33258 staining. The expression of Bcl-2 and Bax proteins was detected by immunohistochemical staining. The cell cycle and the expression of p53 protein were measured by flow cytometry, and the proliferation index (PI) was calculated. RESULTS：Compared with sham group, splenic tissue injury appeared in the shocked rats. The apoptotic cells and the expression of Bax and p53 in shock group were increased, while Bcl-2 expression was decreased. The percentage of G2/M cells in shock group was decreased. Compared with shock group, the splenic tissue damage in shock+drainage group was significantly attenuated. Moreover, the number of apoptotic cells, the percentage of G0/G1 cells, and the expression of Bax and p53 were obviously decreased, and the G2/M cells, Bcl-2 protein expression and PI were significantly increased in shock+drainage group. CONCLUSION: PSML drainage alleviates splenic injury in hemorrhagic shock rats, which may be related to reducing the apoptosis of splenocytes.     

Role of NF-κB in inducing HEL cell proliferation and apoptosis during human cytomegalovirus infection

AIM:To investigate whether human cytomegalovirus(HCMV) regulate human embryonic lung fibroblast(HEL) cell proliferation and apoptosis by activating NF-κB.METHODS:Immunohistochemistry and Western blot analysis were used to detect the NF-κB translocation and/or Bcl-2 and the levels of I-κBα during HCMV infection. Apoptotic cell were examined by flow cytometry, and the HEL cell proliferation was determined by MTT.RESULTS:The levels of NF-κB in the nucleus reached highly 48 h postinfection, and the levels of I-κBα were low 24 h postinfection. The activity of NF-κB was inhibited 120 h postinfection. The levels ofbcl-2was accorded with the activity of NF-κB. HCMV promoted HEL cells to proliferate before 72 h postinfection and induced apoptosis 120 h postinfection.CONCLUSION:NF-κB plays a role in HEL cell proliferation and apoptosis during HCMV infection, and it involves in the pathological mechanisms of diseases associated with HCMV infection.     

Regulatory effect of miRNA enfolded in microparticles on endothelial cells

Endothelial cells are the cells lining the inner surfaces of blood vessels. They build up a single cell layer and play an important role in the regulation of vascular functions and the maintenance of homeostasis. The activation or injury of endothelial cells is associated with multiple diseases, including hypertension, atherosclerosis, cancer, diabetes, etc. Recent studies have found that microparticles are involved in the process of endothelial cell injury, thus playing a part in the development of many diseases. miRNAs enfolded in the microparticles have become importance in recent years. Moreover, recent studies also found that the concentration of the miRNAs enfolded in the microvesicles is higher than that of the miRNAs in the plasma, which means that the microparticles are the main form of miRNAs present in peripheral circulatory system. This article is to review the recent research progress in microparticle-encapsulated miRNAs and their regulatory effect on endothelial cell injury.