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Long non-coding RNAs (lncRNA) are a class of non-coding RNA with a length of more than 200 nucleotide, it is known that lncRNA can regulate gene expression at epigenetic, transcriptional and post transcriptional levels. Recent studies have shown that lncRNA is an important regulator of atherosclerosis (AS) and plays an important role in the pathogenesis of AS. This paper aims to comprehensively explore the mechanism of lncRNA in AS and summarize new biomarkers for AS diagnosis, we focused on the research progress of some key lncRNA in regulating the function of endothelial cells, smooth muscle cells, and monocytes and macrophages through literature review. Furthermore, this review discusses the potential clinical diagnostic value of lncRNA as biomarker in coronary heart disease (CHD), acute myocardial infarction, and heart failure (HF). LncRNA is expected to become a new class of clinically relevant biomarker, which might be useful for the prediction, diagnosis, prognosis and risk stratification of AS and cardiovascular diseases.
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Objective:To investigate the effect and mechanism of miR-195 regulating FOXK1 gene and PI3K/Akt pathway on stomach adenocarcinoma proliferation, invasion and migration ability.Methods:Public database samples were employed to analyze the expression differences and prognostic significance of miR-195 in stomach adenocarcinoma. After overexpression of mir-195-5p in two cell lines, MGC803 and AGS, altered cell proliferation, invasion, and migration abilities were detected by Alamar Blue, Wound healing, and Transwell assays. The potential target genes and binding sites of miR-195 were predicted by the starBase. Western blot was used to detect the expression levels of foxk1 and phosphorylation sites in the PI3K/Akt pathway of target genes after overexpression of mir-195-5p. A Dual-luciferase reporter assay was used to verify the relationship between mir-195-5p and foxk1. Statistical analyses were performed with IBM SPSS 22 software and R 4.0.3.Results:Our results showed a significant over-expression of miR-195 in the tumor tissues, compared with the paired normal tissues ( P<0.001) , which could inhibit the proliferation and invasion of stomach carcinoma cells and significantly correlated with survival ( P=0.011) . Moreover, our study indicated that miR-195 depressed the expression of FOXK1 and significantly reduced the activation of the PI3K/Akt pathway, which had a negative effect on the proliferation and invasion of stomach carcinoma cells. The phosphorylated Akt (s473 site) expression in the PI3K/Akt pathway was significantly decreased after overexpression of miR-195. Conclusion:Overall, our studies clarify the important function of the miR-195 in the diagnosis and therapy of patients with stomach carcinoma and reveal the FOXK1 and PI3K/Akt pathway regulation by the miR-195, which are of important clinical significance in the differential diagnosis.
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As a critical factor of atherosclerosis (AS), oxidized low-density lipoprotein (oxLDL) plays a crucial role in damaging vascular endothelial cells, promoting monocyte adhesion, inducing formation of foam cells and thrombosis. Many scholars have found that oxLDL could be used as a circulating biomarker for atherosclerotic cardiovascular disease. In this manuscript, research progress on the mechanism of oxLDL in the initiation and development of atherosclerosis, as well as using oxLDL as a diagnostic biomarker of atherosclerosis related diseases were systemically reviewed.
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Preeclampsia (PE) is a pregnancy-specific systemic multi-organ syndrome. Immune tolerance is very important for the establishment and maintenance of normal pregnancy. More and more studies have proved that the disorder of the complement system is related to the occurrence and development of PE. Complement molecules may be potential markers for PE screening and diagnosis. This review briefly summarized the role and research progress of the complement system in PE, to provide references for the complement molecules as clinical diagnostic markers and prevention target of PE.
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Objective To investigate the effects of hypoxic conditions on expressions of hypoxia-inducible factor 1α (HIF-1α) and P-glycoprotein (P-gp),and the relationship between HIF-1α and P-gp.Methods Tumor tissues from 54 cases of patients with colonic neoplasm in Xingtai People's Hospital were selected after operation from June 2013 to June 2015.The expressions of HIF-1α and P-gp in colonic tumor tissues were detected by using immunohistochemistry,and their correlations to clinical and pathologic features were analysed.The expressions of HIF-1α and P-gp in colonic tumor cell lines under normoxia and hypoxia conditions were detected by using cell smear method,and correlation between HIF-1α expression and P-gp expression was analysed.Results Among tumor tissues from 58 cases of patients with colonic neoplasm,the positive rate of HIF-1α expression was 58.62％,and that of P-gp expression was 46.55％.The positive rates of HIF-1α and P-gp expressions of patients on the Dukes stage C+D were significantly higher than those of patients on A+B phase (P＜0.05).Additionally,the positive rates of HIF-1α and P-gp expressions of patients with lymphatic metastasis were significantly higher than those of patients without lymphatic metastasis (P＜0.05).The HIF-1α expression was positively correlated with the P-gp expression (r=0.574,P＜0.01).For the same cell lines,the expression levels of HIF-1α and P-gp under hypoxia condition were significantly higher than those under normoxia condition,there were statistically significant differences (P＜0.01).While,under the same oxygen conditions,no statistically significant difference was found in expression levels of HIF-1 and P-gp among different colonic tumor cell lines (P＞0.05).Conclusion Overexpression and coexpression of HIF-1α and P-gp exist in colon cancer.The expression levels of HIF-1α and P-gp in patients with different Dukes stages and patients with or without lymph node metastasis are significantly different,and positive correlation is observed between the expression of HIF-1α and P-gp.Hypoxia condition can induce an increase in expressions of HIF-1α and P-gp in colonic tumor cells.
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Objective To investigate the effect of glutamine in combination with umbilical cord blood mesenchymal stem cells ( MSCs) transplantation on intestinal ischemia-reperfusion injury in rats.Methods Umbilical cord blood mesenchymal stem cells were isolated, and were labeled with CM-DiI fluorescent dye.Eighty Sprague-Dawley rats were randomly divided into normal control group, ischemia reperfusion injury group, glutamine group, MSCs transplantation group and combined group with 15 rats in each group.The control group received saline enema.The injury group was treated with TNBS ( ethanol dilution) enema.The glutamine group at 1 h after TNBS received intravenous injection of 0.45 g/kg glutamine.The rats of MSCs transplantation group had tail vein injection of 1 ×1010/L umbilical cord blood mesenchymal stem cell suspension, and the combined group received intravenous injection of glutamine 0.45 g/kg and 1 ×1010/L umbilical cord blood mesenchymal stem cell suspension.ELISA was used to detect the midgut fatty acid binding protein (iFABP), interleukin 6 (IL-6), and superoxide dismutase (SOD) content in the rat serum.The water content of intestinal tissue was detected at 1 h and 3 h after reperfusion in each group.The expressions of NF-kB, Bcl-2 and caspase-3 mRNA and proteins in the rat intestinal epithelial cells after treated with glutamine in combination with MSCs were detected by RT-PCR and Western blot assays.Results The fluorescent tracer method revealed that the transplanted MSCs cells were distributed in the intestinal mucosal lymphoid tissues and glandular epithelial cells, indicating that MSCs might be involved in the repair process of intestinal ischemia-reperfusion injury.The content of serum IFABP and IL-6 in the injured group was significantly higher than that in the control group, while significantly reduced in the glutamine group, MSCs transplantation group and combined group, with the most obvious in the combined group.The content of SOD in the injury group was significantly lower than that in the control group, and significantly increased than that in the glutamine group, MSCs transplantation group, with the most striking in the combined group ( P0.05).Compared with the control group, the caspase-3 and NF-kB mRNA and protein expressions in the intestinal mucosal epithelial cells of the injury group were significantly increased, and the expressions of Bcl-2 mRNA and protein were significantly reduced ( P 0.05), but there was a significant difference between these two groups and the combined group (P<0.05).Conclusions After treated with glutamine and MSCs transplantation, the degree of intestinal ischemia reperfusion injury is obviously reduced in rats.It may be mediated through inhibiting the expression of caspase-3 and NF-kB and promoting the expression of Bcl-2.
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BACKGROUND:Bone marrow mesenchymal stem cel s can repair intestinal ischemia-reperfusion injuny by interfering inflammatory reactions after intestinal ischemia-reperfusion to protect intestinal barrier functions. In recent years, umbilical cord blood mesenchymal stem cel s are gradual y used as a substitute source of bone marrow mesenchymal stem cel s. OBJECTIVE:To investigate the effects of umbilical cord blood mesenchymal stem cel s on acute intestinal ischemia-reperfusion injury. METHODS:Umbilical cord blood mesenchymal stem cel s were induced, isolated in vitro and tracked by CM-DiI fluorescent labeling. Sixty-three Sprague-Dawley rats were equivalently randomized into three groups:control group received normal saline enema, intestinal ischemia-reperfusion injury group with ethanol diluted trinitro-benzene-sulfonic acid and transplantation group administrated with 1×1010/L umbilical cord blood mesenchymal stem cel suspension via the tail vein at 1 hour after trinitro-benzene-sulfonic acid modeling. At 3 days after transplantation, colon tissues were removed in each group to observe pathological changes of the intestinal tract by hematoxylin-eosin staining. Besides, expression of leptin mRNA in the colon tissues and cyclooxygenase-2 in the mucosa were detected by RT-PCR and immunohistochemistry method, respectively. RESULTS AND CONCLUSION:Transplanted umbilical cord blood mesenchymal stem cel s distributed in the intestinal lymphoid tissue and among glandular epithelial cel s, suggesting that these stem cel s might be involved in the process of intestinal ischemia-reperfusion injury repair. Compared with the control group, intestinal injury in the injury group was significantly aggravated, and most intestinal epithelial cel s shed;and the transplantation group appeared to have significantly reduced intestinal damage and significantly less cel shedding. Expression of leptin mRNA was significantly higher in the injury group than the transplantation group fol owed by the control group, and there were significant differences among the three groups (P<0.05). Additional y, expression of cyclooxygenase-2 in the injury group was significantly higher than that in the control group (P<0.05);compared with the injury group, expression of cyclooxygenase-2 was significantly lower in the transplantation group (P<0.05). To conclude, leptin and cyclooxygenase-2 may be involved in acute intestinal ischemia-reperfusion injury, and umbilical cord blood mesenchymal stem cel transplantation significantly lessens intestinal ischemia-reperfusion injury, which provides an experimental basis for human treating acute intestinal ischemic injury.
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Exosomes are nanosized lipid vesicles released from cells .They are believed to contain proteins, lipids and nucleic acid cargos , and are capable of deliver their cargos to recipient cells , which in turn alter the expression of genes in neighboring cells .An increasing body of evidence indicates that they play a pivotal role in cell-to-cell communication , which is hijacked during various physiological and pathological conditions , such as myocardial damage , angiogenesis , cardiac remodeling and atherogenesis plaque formation .Further research of intercellular communication mediated by exosomes may potentially aid in the possible application of exosomes for biomarker discovery , curative effects , as well as prognosis of cardiovascular diseases , even the use of exosomes as a therapeutic drug delivery system on the basis of the exosome′s ability to target specific cells , and transfer genetic materials.