MicroRNA-21 in the pathogenesis of acute kidney injury

Acute kidney injury(AKI),associated with significant mor-bidity and mortality,is widely known to involve epithelial apoptosis,excessive inflammation,and fibrosis in re-sponse to ischemia or reperfusion injury,which results in either chronic pathological changes or death.Therefore,it is imperative that investigations are conducted in order to fi nd effective,early diagnoses,and therapeutic targets needed to help prevent and treat AKI.However,the mech-anisms modulating the pathogenesis of AKI still remain largely undetermined.MicroRNAs(miRNAs),small non-coding RNA molecules,play an important role in several fundamental biological and pathological processes by a post transcriptional regulatory function of gene expres-sion.MicroRNA-21(miR-21)is a recently identifi ed,typi-cal miRNA that is functional as a regulator known to be involved in apoptosis as well as inflammatory and fi brotic signaling pathways in AKI.As a result,miR-21 is now considered a novel biomarker when diagnosing and treat-ing AKI.This article reviews the correlative literature and research progress regarding the roles of miR-21 in AKI.

PD-1 Involvement in Peripheral Blood CD8+T Lymphocyte Dysfunction in Patients with Acute-on-chronic Liver Failure

Background and Aims:Programmed cell death-1(PD-1)plays an important role in downregulating T lymphocytes but the mechanisms are still poorly understood.This study aimed to explore the role of PD-1 in CD8^(+)T lymphocyte dysfunction in hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF).Methods:Thirty patients with HBV-ACLF and 30 healthy controls(HCs)were recruited.The differences in the numbers and functions of CD8^(+)T lymphocytes,PD-1 and glucose transporter-1(Glut1)expression from the peripheral blood of patients with HBV-ACLF and HCs were analyzed.In vitro,the CD8^(+)T lymphocytes from HCs were cultured(HC group)and the CD8^(+)T lymphocytes from ACLF patients were cultured with PD-L1-IgG(ACLF+PD-1 group)or IgG(ACLF group).The numbers and functions of CD8^(+)T lymphocytes,PD-1 expression,glycogen uptake capacity,and Glut1,hexokinase-2(HK2),and pyruvate kinase(PKM2)expression were analyzed among the HC group,ACLF group and ACLF+PD-1group.Results:The absolute numbers of CD8^(+)T lymphocytes in the peripheral blood from patients with HBVACLF were lower than in the HCs(p<0.001).The expression of PD-1 in peripheral blood CD8^(+)T lymphocytes was lower in HCs than in patients with HBV-ACLF(p=0.021).Compared with HCs,PD-1 expression was increased(p=0.021)and Glut1 expression was decreased(p=0.016)in CD8^(+)T lymphocytes from the HBV-ACLF group.In vitro,glycogen uptake and functions of ACLF CD8^(+)T lymphocytes were significantly lower than that in HCs(p=0.017;all p<0.001).When PD-1/PD-L1 was activated,the glycogen uptake rate and expression levels of Glut1,HK2,and PKM2 showed a decreasing trend(ACLF+PD-1 group compared to ACLF group,all p<0.05).The functions of CD8^(+)T lymphocytes in the ACLF+PD-1 group[using biomarkers of Ki67,CD69,IL-2,interferon-gamma,and tumor necrosis factor-alpha-were lower than in the ACLF group(all p<0.05).Conclusions:CD8^(+)T lymphocyte dysfunction is observed in patients with HBV-ACLF.PD-1-induced T lymphocyte dysfunction might involve glycolysis inhibition.

Gender differences in the relationship between plasma lipids and fasting plasma glucose in non-diabetic urban Chinese popula- tion： a cross-section study

The association between dyslipidemia and elevated fasting glucose in type 2 diabetes is well known. In non-diabetes, whether this association still exists, and whether dyslipidemia is an independent risk factor for high fasting plasma glucose （FPG） levels are not clear. This cross-sectional study recruited 3460 non-diabetic Chinese subjects （1027 men, and 2433 women, aged 35-75 years old） who participated in a health survey. Men and women were classified into tertiles by levels of plasma lipids respectively. In women, the prevalence of impaired fasting glucose （IFG） was decreased with increased HDL-C. A stepwise increase in HDL-C was associated with decreasing FPG levels （lowest tertiles, FPG： 5.376 ± 0.018; middle tertiles, 5.324± 0.018; highest tertiles, 5.276±0.018mmol/L; P = 0.001）. Reversely, FPG levels increased from lowest tertiles to highest tertiles of LDL-C, TC, and TG. we found that women in the first tertile with lower HDL-C level had a 1.75-fold increase in risk of IFG compared with non-diabetic women in the third tertile with higher HDL-C level （OR： 1.75; 95% CI： 1.20-2.56）. In men, no significant association was found. We took age, BMI, waist/hip ratio, education, smoking, alcohol drinking, and physical exercise as adjusted variables. In Chinese non-diabetic women, dyslipidemia is independently associated with high levels of FPG; TG, HDL-C, and LDL-C are predictors of IFG independent of BMI and waist/hip ratio.

Increased dopamine and its receptor dopamine receptor D1 promote tumor growth in human hepatocellular carcinoma

Background:Dopamine and dopamine receptor D1(DRD1),a member of the dopamine receptor family,have been indicated to play important roles in cancer progression,but dopamine secretion in hepatocellular carcinoma(HCC)and the effects of DRD1 on HCC remain unclear.This study was designed to explore the contribution of the dopaminergic system to HCC and determine the relationship between DRD1 and prognosis in HCC patients.Methods:The dopamine metabolic system was monitored using enzyme-linked immunosorbent assays(ELISAs).The expression of DRD1 was detected by microarray analysis,immunohistochemistry(IHC),and quantitative real-time PCR(qRT-PCR).Stable DRD1 knockout and overexpression cell lines were established for investigation.Transwell,colony formation,and Cell Counting Kit 8(CCK8)assays were performed to assess the malignant behaviors of cancer cells.The cAMP/PI3K/AKT/cAMP response element-binding(CREB)signaling pathway was evaluated by Western blot.This pathway,which is agitated by DRD1 in striatal neurons,had been proven to participate in tumor progression.Xenograft HCC tumors were generated for in vivo experiments.Results:Dopamine secretion increased locally in HCC due to an imbalance in dopamine metabolism,including the upregulation of dopa decarboxylase(DDC)and the downregulation of monoamine oxidase A(MAOA).Dopamine promoted the proliferation and metastasis of HCC.DRD1 was highly expressed in HCC tissues and positive DRD1 expression was related to a poor prognosis in HCC patients.The upregulation of DRD1 agitated malignant activities,including proliferation and metastasis in HCC by regulating the cAMP/PI3K/AKT/CREB pathway,and the downregulation of DRD1 had opposing effects.The effects of dopamine on HCC was reversed by depleting DRD1.SCH23390,a selective DRD1 antagonist,inhibited the proliferation and metastasis of HCC cells both in vitro and in vivo.Conclusion:Dopamine secretion was locally increased in HCC and promoted HCC cell proliferation and metastasis.DRD1 was found to exert positive effects on HCC progression and play a vital role in the dopamine system,and could be a potential therapeutic target and prognostic biomarker for HCC.