Hydrogen sulphide reduced the accumulation of lipid droplets in cardiac tissues of db/db mice via Hrd1 S-sulfhydration.

Accumulation of lipid droplets (LDs) induces cardiac dysfunctions in type 2 diabetes patients. Recent studies have shown that hydrogen sulphide (H2 S) ameliorates cardiac functions in db/db mice, but its regulation on the formation of LDs in cardiac tissues is unclear. Db/db mice were injected with NaHS (40 µmol·kg-1 ) for twelve weeks. H9c2 cells were treated with high glucose (40 mmol/L), oleate (200 µmol/L), palmitate (200 µmol/L) and NaHS (100 µmol/L) for 48 hours. Plasmids for the overexpression of wild-type Hrd1 and Hrd1 mutated at Cys115 were constructed. The interaction between Hrd1 and DGAT1 and DGAT2, the ubiquitylation level of DGAT1 and 2, the S-sulfhydration of Hrd1 were measured. Exogenous H2 S ameliorated the cardiac functions, decreased ER stress and reduced the number of LDs in db/db mice. Exogenous H2 S could elevate the ubiquitination level of DGAT 1 and 2 and increased the expression of Hrd1 in cardiac tissues of db/db mice. The S-sulfhydration of Hrd1 by NaHS enhanced the interaction between Hrd1 and DGAT1 and 2 to inhibit the formation of LD. Our findings suggested that H2 S modified Hrd1 S-sulfhydration at Cys115 to reduce the accumulation of LDs in cardiac tissues of db/db mice.

Hydrogen sulphide ameliorating skeletal muscle atrophy in db/db mice via Muscle RING finger 1 S-sulfhydration.

Muscle atrophy occurs in many pathological states, including cancer, diabetes and sepsis, whose results primarily from accelerated protein degradation and activation of the ubiquitin-proteasome pathway. Expression of Muscle RING finger 1 (MuRF1), an E3 ubiquitin ligase, was increased to induce the loss of muscle mass in diabetic condition. However, hydrogen sulphide (H2 S) plays a crucial role in the variety of physiological functions, including antihypertension, antiproliferation and antioxidant. In this study, db/db mice and C2C12 myoblasts treated by high glucose and palmitate and oleate were chose as animal and cellular models. We explored how exogenous H2 S attenuated the degradation of skeletal muscle via the modification of MuRF1 S-sulfhydration in db/db mice. Our results show cystathionine-r-lyase expression, and H2 S level in skeletal muscle of db/db mice was reduced. Simultaneously, exogenous H2 S could alleviate ROS production and reverse expression of ER stress protein markers. Exogenous H2 S could decrease the ubiquitination level of MYOM1 and MYH4 in db/db mice. In addition, exogenous H2 S reduced the interaction between MuRF1 with MYOM1 and MYH4 via MuRF1 S-sulfhydration. Based on these results, we establish that H2 S prevented the degradation of skeletal muscle via MuRF1 S-sulfhydration at the site of Cys44 in db/db mice.

Circular RNA circC3P1 suppresses hepatocellular carcinoma growth and metastasis through miR-4641/PCK1 pathway.

In the recent years, increasing evidences identify circular RNAs (circRNAs) as a class of important regulators in various human cancers. Nevertheless, the functions and mechanisms of most circRNAs in cancer cells remain largely unknown. In this study, we found out a significantly downregulated circRNA circC3P1 in hepatocellular carcinoma (HCC) tissues compared to adjacent normal tissues. And our results indicated that circC3P1 expression level was negatively correlated with TNM stage, tumor size and vascular invasion in HCC. Moreover, we found that circC3P1 overexpression dramatically inhibited the proliferation, migration and invasion of HCC cells in vitro and in vivo. In terms of mechanism, we found that circC3P1 could promote PCK1 expression through sponging miR-4641 in HCC cells. We showed that miR-4641 expression was negatively correlated with that of either circC3P1 or PCK1 in HCC tissues. Finally, by functional experiments, we demonstrated that knockdown of PCK1 significantly attenuated the effects of circC3P1 overexpression on HCC cell proliferation, migration and invasion. In summary, our findings illustrated that circC3P1 acts as a tumor suppressor via enhancing PCK1 expression by sponging miR-4641 in HCC.

Maslinic acid protects against lipopolysaccharide/d-galactosamine-induced acute liver injury in mice.

Acute liver injury is a life-threatening syndrome that often caused by hepatocyte damage. In this study, we investigated the protective effects of maslinic acid (MA) on lipopolysaccharide (LPS)/d-galactosamine (D-gal)-induced acute liver injury and clarified its mechanism. Mice acute liver injury model was induced by given LPS and D-gal and MA was given intraperitoneally 1 h before LPS and D-gal. Our results showed that MA protected against liver injury by attenuating liver histopathologic changes, serum AST and ALT levels. The increased inflammatory cytokines TNF-α and IL-6 in serum and liver tissues were also inhibited by MA. The level of MDA and the activity of MPO in liver tissues were up-regulated by LPS/D-gal and dose-dependently inhibited by MA. Furthermore, MA attenuated hepatic NF-κB protein expression and increased hepatic Nrf2 and HO-1 protein expression. Taken together, MA offers a protective role against LPS/D-gal-induced liver injury through suppressing NF-κB and activating Nrf2 signaling pathways.

Interactions between CYP1A1 polymorphisms and cigarette smoking are associated with the risk of hepatocellular carcinoma: evidence from epidemiological studies.

The Cytochrome P-450 1A1 (CYP1A1) gene has been implicated in the etiology of hepatocellular carcinoma (HCC). However, the results have been inconsistent. In this study, a meta-analysis was performed to clarify the associations of polymorphisms in CYP1A1 gene with HCC risk. Published literature from PubMed, Embase, CNKI and Wanfang Data were retrieved. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model. Eight studies (1,752 cases and 2,279 controls) for Ile-Val polymorphism and eight studies (933 cases and 1,449 controls) for MspI polymorphism were identified. The results showed that there was no statistically significant association between the Ile-Val polymorphism and HCC risk under all genetic models (co-dominant model: Val/Val vs. Ile/Ile: OR = 1.62, 95% CI 0.96-2.72 and Ile/Val vs. Ile/Ile: OR = 1.15, 95% CI 0.87-1.52; dominant model: OR = 1.25, 95% CI 0.92-1.70; recessive model: OR = 1.48, 95% CI 0.99-2.21). The MspI polymorphism was also not associated with HCC risk (co-dominant model: m2m2 vs. m1m1: OR = 1.09, 95% CI 0.83-1.42 and m1m2 vs. m1m1: OR = 1.30, 95% CI 1.05-1.61; dominant model: OR = 1.20, 95% CI 0.99­1.45; recessive model: OR = 0.94, 95% CI 0.74-1.18). However, the significant associations were found between both the Ile­Val and MspI polymorphisms and HCC risk among the cigarette smoking subjects (Ile-Val: OR = 1.40, 95% CI 1.06-1.85; MspI: OR = 2.65, 95% CI 1.47-4.77). The present meta-analysis indicated that the MspI and Ile-Val polymorphisms of CYP1A1 may play important roles in increasing susceptibility to smoking-related HCC.

Effects of radiofrequency ablation combined with transarterial chemoembolization and antiviral therapy on the prognosis and quality of life in primary chronic HBV-related liver cancer.

PURPOSE: To investigate the effects of radiofrequency ablation (RFA) combined with transarterial chemoembolization (TACE) and antiviral therapy on the prognosis and quality of life in primary chronic hepatitis B virus (HBV)-related liver cancer. METHODS: A total of 80 hepatitis B patients complicated with hepatocellular carcinoma treated in our hospital from March 2016 to February 2018 were selected and divided into the control group (n=40) and the observation group (n=40) using a random number table. The patients in the control group were treated with RFA combined with TACE, while those in the observation group were additionally treated with entecavir. The HBV-DNA load and alpha fetoprotein (AFP) level during intervention and the liver function before and after intervention were compared between the two groups. The patients were followed up for 2 years after treatment, the clinical therapeutic effects in both groups were recorded, and the correlations of HBV-DNA load, AFP level and alanine aminotransferase (ALT) level with the survival time of patients were analyzed. RESULTS: At 1 and 3 months after intervention, the HBV-DNA load in the observation group was significantly lower than that before intervention (p<0.05), and it was also significantly lower than in the control group (p<0.05). At 1 and 3 months after intervention, the AFP level was lowered in both groups compared with that before the intervention (p<0.05), and it was also lower in the observation group than in the control group (p<0.05). After intervention, the levels of total bilirubin (Tbil), aspartate aminotransferase (AST) and ALT in the observation group were lower than those before the intervention (p<0.05), and they were also lower than those in the control group (p<0.05). Moreover, the disease progression in the observation group was significantly lower than in the control group, and the 1-year and 2-year survival in the observation group was longer compared with the control group. The HBV-DNA load, AFP level and ALT level were negatively correlated with the survival of patients (p<0.05). CONCLUSIONS: The RFA combined with TACE and regular antiviral therapy for HBV-related liver cancer is of significance in reducing the HBV-DNA load and tumor markers, improving the liver function, promoting the overall clinical therapeutic effect and prolonging the survival of patients.

The Circular RNA Cdr1as Act as an Oncogene in Hepatocellular Carcinoma through Targeting miR-7 Expression.

CircRNAs are a class of endogenous RNA that regulates gene expression at the post-transcriptional or transcriptionallevel through interacting with other molecules or microRNAs. Increasing studies have demonstrated that circRNAs play a crucial role in biology processes. CircRNAs are proved as potentialbiomarkers in many diseases including cancers. However, the role of Cdr1as in Hepatocellular carcinoma (HCC) remains to be elucidated. We demonstrated that Cdr1as expression was upregulated in HCC tissues compared with the adjacent non-tumor tissues. In addtion, miR-7 expression was downregulated in HCC tissues compared with the adjacent non-tumor tissues. Moreover, the expression level of miR-7 was inversely correlated with that in HCC tissues. Knockdown of Cdr1as suppressed the HCC cell proliferation and invasion. Overexpression of miR-7 inhibited the HCC cell proliferation and invasion. Overexpression of miR-7 could suppress the direct target gene CCNE1 and PIK3CD expression. Knockdown of Cdr1as suppressed the expression of miR-7 and also inhibited the CCNE1 and PIK3CD expression. Furthermore, knockdown of Cdr1as suppressed the HCC cell proliferation and invasion through targeting miR-7. These data suggested that Cdr1as acted as an oncogene partly through targeting miR-7 in HCC.

miR-454 functions as an oncogene by inhibiting CHD5 in hepatocellular carcinoma.

Previous studies showed that miR-454 acted as an oncogene or tumor suppressor in cancer. However, its function in HCC remains unknown. In this study, we found that miR-454 expression was upregulated in HCC cell lines and tissues. Knockdown of miR-454 inhibited HCC cell proliferation and invasion and epithelial mesenchymal transition (EMT), whereas overexpression of miR-454 promoted HCC cell proliferation and invasion and EMT. Furthermore, we identified the CHD5 as a direct target of miR-454. CHD5 was downregulated in HCC tissues and cell lines and the expression level of CHD5 was inversely correlated with the expression of miR-454 in HCC tissues. In addition, knockdown of miR-454 inhibited the growth of HepG2-engrafted tumors in vivo. Taken together, these results indicated that miR-454 functioned as an oncogene in HCC.

[The level of IL-8 in the serum of patients suffering from chronic hepatic diseases and primary hepatocellular carcinoma].

OBJECTIVE: To explore the relation between the pathogenesis and IL-8 level in the chronic hepatic disease and primary hepatocellular carcinoma. METHODS: 5ml venous blood was with drawn from 80 hospitaliged patients with different types of hepatic diseases and 14 healthy people. The serum was separated from the blood and then kept at -40 degrees Centigrade, and finally detected for IL-8 by ELISA. RESULTS: There was an obvious difference among the IL-8 level in the serum from different types of hepatic disease patients. The IL-8 level was 75.80 microg/L 33.39 microg/L in chronic virus hepatitis and it was 89.54 microg/L 13.24 microg/L for primary hepatoma patients (t=10.48 and 4.01, respectively, P<0.01, as compared with control group). CONCLUSIONS: There is a close relation between the level of IL-8 in serum and the state of illness. For patients with chronic hepatic diseases and primary hepatocellular carcinoma, the higher the IL-8 level is, the more serious the patients' condition, the worse the prognosis, and the higher the death rate would be.