Hepatocellular carcinoma (HCC) is the most commonmalignancy. Exsome plays a significant role in the elucidation of signal transduction pathways between hepatoma cells, angiogenesis and early diagnosis of HCC. Exosomes are small vesicular structures that mediate interaction between different types of cells, and contain a variety of components (including DNA, RNA, and proteins). Numerous studies have shown that these substances in exosomes are involved in growth, metastasis and angiogenesis in liver cancer, and then inhibited the growth of liver cancer by blocking the signaling pathway of liver cancer cells. In addition, the exosomal substances could also be used as markers for screening early liver cancer. In this review, we summarized to reveal the significance of exosomes in the occurrence, development, diagnosis and treatment of HCC, which in turn might help us to further elucidate the mechanism of exosomes in HCC, and promote the use of exosomes in the clinical diagnosis and treatment of HCC.
Abstract. To explore the relationship between serum thyrotropin and components of metabolic syndrome in a Chinese cohort. A total of 1534 adult inhabitants in DaDong district of Shenyang were asked to fulfill the questionnaire, complete physical examination and OGTT. Blood samples were collected to test thyrotropin (TSH), fasting plasma glucose (FPG), OGTT 2h PG, fasting insulin (FINS), triglyceride (TG) and high density lipoprotein cholesterol (HDL-C). Serum TSH in metabolic syndrome group was higher than that in the non-metabolic syndrome group (2.54 mIU/L vs. 2.22 mIU/L, p<0.05). TG level increased significantly in subclinical hypothyroid group compared with euthyroid subjects (1.73±0.12 mmol/L vs.1.47±0.03 mmol/L, p<0.05), and HDL-C decreased significantly in patients with subclinical hypothyroidism compared with euthyroid subjects (1.26±0.27 mmol/L vs. 1.33±0.27 mmol/L, p<0.05). The prevalence of hypertension was higher in the subclinical hypothyroid group than that in euthyroid group (42.86% vs. 33.2%, p<0.05). The serum TSH within the reference range was positively related with the prevalence of overweight/obesity. Slight increase in serum TSH maybe a risk factor for metabolic syndrome.
It is still controversial whether subclinical hypothyroidism and euthyroidism affect blood pressure. The study aimed to explore the relationship between different levels of thyroid-stimulating hormone (TSH) and blood pressure in the participants with subclinical hypothyroidism and euthyroidism. A total of 1319 participants were administered a questionnaire survey, and their blood pressure, height and body weight measurements were taken. Blood samples were taken to test serum TSH. FT3 and FT4 were further examined if TSH was abnormal. Participants were divided into euthyroid group and subclinical hypothyroidism group. Euthyroid group was further divided into three groups: group A (TSH 0.3-0.99 mIU l À1 ), group B (TSH 1.0-1.9 mIU l À1) and group C (TSH 1.91-4.8 mIU l À1 ). Results showed that different levels of serum TSH had no relation with systolic blood pressure (SBP) and diastolic blood pressure (DBP). The prevalence of hypertension in subclinical hypothyroidism group was significantly higher than euthyroid group in females (41.3 vs 25.6%, Po0.05). The risk of hypertension in subclinical hypothyroidism group was significantly higher than that in the euthyroid group after adjusted for age, gender, smoking status, HOMA-IR (homoeostasis model assessment of insulin resistance) and body mass index (odds ratio (OR) ¼ 1.753, 95% confidence interval (CI) 1.067-2.879, P ¼ 0.027). This association was stronger in females (OR ¼ 3.545, 95% CI 1.576-7.975, P ¼ 0.004), but there was no statistical significance in males. Within normal range of TSH, both SBP and DBP were similar among the three groups. The prevalence and risk of hypertension were also similar among the three groups. In conclusion, the prevalence of hypertension in subclinical hypothyroidism group was significantly higher than in euthyroid group in females. Change of TSH in normal range did not affect blood pressure.
Methionine aminopeptidase-2 (MetAP2) processes N-terminal methionine from nascent cellular proteins. Inhibition of MetAP2 has been shown to block angiogenesis and suppress tumor growth in preclinical tumor models. However, the biological role of MetAP2 in cancer is not well understood. We examined the effect of three distinct chemical classes of MetAP2 inhibitors on the growth of a panel of human cancer cells in vitro. All MetAP2 inhibitors caused inhibition of tumor cell growth in both anchorage-dependent and, particularly, in anchorage-independent manner. These data prompted us to examine the possible roles of MetAP2 in cancers. Ectopic expression of MetAP2 in NIH-3T3 cells caused transformation, evidenced by the formation of foci in monolayer culture and growth of large colonies in soft agar. Overexpression of MetAP2 in an immortalized bronchial epithelial cell line NL20 accelerated growth. These phenotypes induced by the overexpression of MetAP2 were reversed by the treatment with MetAP2 inhibitors, indicating that the catalytic function of MetAP2 was essential. Accordingly, overexpression of a catalytically inactive MetAP2 resulted in growth retardation of HT1080 tumor cells, suggesting a dominant-negative role of the inactive MetAP2 mutant. Finally, we analysed the expression of MetAP2 in patient cancer samples by immunohistochemistry. Moderate-to-high staining was identified in the majority of breast, colon, lung, ovarian and prostate carcinomas examined. These data suggest that MetAP2 plays an important role in tumor cell growth and may contribute to tumorigenesis.
Background Red blood cell distribution width (RDW) has emerged as a prognostic factor for mortality in various diseases. Up to now, few studies have focused on the prognostic value of RDW in patients with diabetic foot ulcers (DFUs). This retrospective cohort study aimed to investigate the impact of RDW and RDW/albumin (ALB) ratio on all-cause mortality in patients with DFUs. Methods This study included 860 patients with DFUs in a tertiary academic hospital. The associations of RDW and RDW/ALB with all-cause mortality were assessed by multivariable cox regression analyses. The pairwise comparisons of receiver operating characteristic (ROC) curves were performed to compare the predictive performance of RDW and RDW/ALB ratio. Harrell’s concordance index, integrated discrimination improvement, and net reclassification improvement were used to estimate the improvements in risk discrimination. Results Patients with high RDW and RDW/ALB had lower overall survival rates (all P < 0.001). The multivariable Cox regression revealed that high RDW [adjusted hazard ratio (HR) 2.426, 95% confidence interval (CI): 1.557–3.778, P < 0.001] and high RDW/ALB (adjusted HR 2.360, 95% CI: 1.414–3.942, P = 0.001) were independent associated with high all-cause mortality. In subgroup analyses, the comparative analysis of ROC curves revealed that the discriminating ability of the RDW/ALB ratio was significantly superior to RDW in patients with no severe DFUs or no severe peripheral artery disease, or in young and middle-aged patients (all P < 0.05). Adding RDW and RDW/ALB ratio to base models improved discrimination and risk reclassification for all-cause mortality. Conclusions RDW and RDW/ALB ratio are robust and independent prognostic markers in patients with DFUs. The RDW/ALB ratio appears to be of more predictive value for mortality in younger and less severely ill patients with DFUs. Both RDW and RDW/ALB ratio can provide incremental predictive value for all-cause mortality over traditional risk factors. RDW and RDW/ALB ratio can be used to identify high-risk patients with DFUs.
Background/Aim: Surgery and chemotherapy treatments of human laryngeal squamous cell carcinoma (HLSCC) may fail due to metastasis, in which epithelial-mesenchymal transition (EMT) plays an important role. TRPP2, a nonselective cation channel, is expressed in various cell types and participates in many biological processes. Here, we show that TRPP2 enhanced metastasis by regulating EMT. Methods: We used immunohistochemistry, western blotting, Ca2+ imaging, transwell and wound healing assays to investigate TRPP2 expression levels in HLSCC tissue, and the role of TRPP2 in invasion and metastasis of a human laryngocarcinoma cell line (Hep2 cell). Results: We found that TRPP2 protein expression levels were significantly increased in HLSCC tissue; higher TRPP2 levels were associated with decreased patient survival time and degree of differentiation and advanced clinical stage. Knockdown of TRPP2 by transfection with TRPP2 siRNA markedly suppressed ATP-induced Ca2+ release, wound healing, and cell invasion in Hep2 cells. Moreover, TRPP2 siRNA significantly decreased vimentin expression but increased E-cadherin expression in Hep2 cells. In the EMT signalling pathway, TRPP2 siRNA significantly decreased Smad4, STAT3, SNAIL, SLUG and TWIST expression in Hep2 cells. Conclusion: We revealed a previously unknown function of TRPP2 in cancer development and a TRPP2-dependent mechanism underlying laryngocarcinoma cell invasion and metastasis. Our results suggest that TRPP2 may be used as a biomarker for evaluating patient prognosis and as a novel therapeutic target in HLSCC.
Orai1, a specific nonvoltage‐gated Ca2+ channel, has been found to be one of key molecules involved in store‐operated Ca2+ entry (SOCE). Orai1 may associate with other proteins to form a signaling complex, which is essential for regulating a variety of physiological functions. In this study, we studied the possible interaction between Orai1 and large conductance Ca2+‐activated potassium channel (BKC a). Using RNA interference technique, we demonstrated that the SOCE and its associated membrane hyperpolarization were markedly suppressed after knockdown of Orai1 with a specific Orai1 siRNA in rat mesenteric artery smooth muscle. Moreover, isometric tension measurements showed that agonist‐induced vasocontraction was increased after Orai1 was knocked down or the tissue was incubated with BKC a blocker iberiotoxin. Coimmunoprecipitation data revealed that BKC a and Orai1 could reciprocally pull down each other. In situ proximity ligation assay further demonstrated that Orai1 and BKC a are in close proximity. Taken together, these results indicate that Orai1 physically associates with BKC a to form a signaling complex in the rat mesenteric artery smooth muscle. Ca2+ influx via Orai1 stimulates BKC a, leading to membrane hyperpolarization. This hyperpolarizing effect of Orai1‐BKC a coupling could contribute to reduce agonist‐induced membrane depolarization, therefore preventing excessive contraction of the rat mesenteric artery smooth muscle in response to contractile agonists.
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