New horizons for the role of RNA N6-methyladenosine modification in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignancy, presenting a formidable challenge to the medical community owing to its intricate pathogenic mechanisms. Although current prevention, surveillance, early detection, diagnosis, and treatment have achieved some success in preventing HCC and controlling overall disease mortality, the imperative to explore novel treatment modalities for HCC remains increasingly urgent. Epigenetic modification has emerged as pivotal factors in the etiology of cancer. Among these, RNA N6-methyladenosine (m6A) modification stands out as one of the most prevalent, abundant, and evolutionarily conserved post-transcriptional alterations in eukaryotes. The literature underscores that the dynamic and reversible nature of m6A modifications orchestrates the intricate regulation of gene expression, thereby exerting a profound influence on cell destinies. Increasing evidence has substantiated conspicuous fluctuations in m6A modification levels throughout the progression of HCC. The deliberate modulation of m6A modification levels through molecular biology and pharmacological interventions has been demonstrated to exert a discernible impact on the pathogenesis of HCC. In this review, we elucidate the multifaceted biological functions of m6A modifications in HCC, and concurrently advancing novel therapeutic strategies for the management of this malignancy.

Endoplasmic reticulum stress and protein degradation in chronic liver disease.

Endoplasmic reticulum (ER) stress is easily observed in chronic liver disease, which often causes accumulation of unfolded or misfolded proteins in the ER, leading to unfolded protein response (UPR). Regulating protein degradation is an integral part of UPR to relieve ER stress. The major protein degradation system includes the ubiquitin-proteasome system (UPS) and autophagy. All three arms of UPR triggered in response to ER stress can regulate UPS and autophagy. Accumulated misfolded proteins could activate these arms, and then generate various transcription factors to regulate the expression of UPS-related and autophagy-related genes. The protein degradation process regulated by UPR has great significance in many chronic liver diseases, including non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), viral hepatitis, liver fibrosis, and hepatocellular carcinoma(HCC). In most instances, the degradation of excessive proteins protects cells with ER stress survival from apoptosis. According to the specific functions of protein degradation in chronic liver disease, choosing to promote or inhibit this process is promising as a potential method for treating chronic liver disease.

[Study on extraction of antioxidant oligopeptide from oyster shell].

OBJECTIVE: To research composition and activity of the organic matters from oyster shell. METHODS: Oyster shell powder was extracted by water. The organic matters were analyzed by biuret method. Then by anion exchange chromatography and reverse C8 column chromatography, oligopeptide extract was obtained from oyster shell and its antioxidant properties was researched. RESULTS: Oyster shell organic matters were mainly composed of oligopeptide constituents and total peptide content was about 38.02%. The product had strong DPPH x free radical and superoxide anion free radical scavenging ability. CONCLUSION: Oligopeptide from oyster shell has good development prospect for antioxidant drug and health protecting food.

[Identification study of raw oyster and calcined ostreae concha].

OBJECTIVE: To identify the differences in characteristics of raw oyster and oysters calcined under different temperatures. METHODS: Identified raw oyster, oysters calcined under different temperatures and calcium carbonate, calcium oxide by differential thermal analysis, infrared spectroscopy and X-ray diffraction analysis. RESULTS: Composition of calcined oysters was closer to calcium carbonate than raw oyster. CONCLUSION: The fingerprints are established and identify raw oyster and calcined oysters.

LncRNA-H19 induces hepatic stellate cell activation via upregulating alcohol dehydrogenase III-mediated retinoic acid signals.

Activation of hepatic stellate cells (HSCs) is a pivotal event in liver fibrosis, characterized by enhanced retinoic acid signals. Although up-regulated retinoic acid signal responds further to maintain HSC activation, the underlying molecular mechanisms are largely unknown. In this study, we sought to investigate the role of lncRNA-H19 in regulation of retinoic acid signals, and to further examine the underlying mechanism in this molecular context. We found that lncRNA-H19 upregulation could enhance retinoic acid signals to induce HSC activation, whereas lncRNA-H19 knockdown completely disturbed retinoic acid signals. Moreover, the activation of retinoic acid signals impaired the lncRNA-H19 knockdown mediated HSC inactivation. Interestingly, we also found that enhanced retinoic acid signals by lncRNA-H19 was associated with a coordinate increase in retinol metabolism during HSC activation. Increased retinol metabolism contributed to obvious lipid droplet consumption. Importantly, we identified that alcohol dehydrogenase III (ADH3) was essential for lncRNA-H19 to enhance retinoic acid signals. The inhibition of ADH3 completely abrogated the lncRNA-H19 mediated retinoic acid signals and HSC activation. Of note, we identified dihydroartemisinin (DHA) as a natural inhibitor for lncRNA-H19. Treatment with DHA significantly decreased the expression of lncRNA-H19, reduced the expression of ADH3, blocked retinoic acid signals, and in turn, inhibited HSC activation. Overall, these results provided novel implications to reveal the molecular mechanism of increased retinoic acid signals during HSC activation, and identify lncRNA-H19/ADH3 pathway as a potential target for the treatment of liver fibrosis.

Diallyl trisulfide attenuates ethanol-induced hepatic steatosis by inhibiting oxidative stress and apoptosis.

Inhibiting the major characteristics of alcoholic fatty liver (AFL) such as lipid accumulation, oxidative stress and apoptosis is a promising strategy of treating AFL. Diallyl trisulfide (DATS) is the major constituent isolated from garlic, which shows promise in the treatment of chronic liver disease. However, the effects of DATS on ethanol-induced liver injury and the related mechanisms remain unclear. The aim of this study was to evaluate the potential protective effects of DATS on AFL and the potential mechanisms. A single intragastric dose of ethanol was given to rats in vivo, while ethanol-stimulated LO2 cells were used as an in vitro model. Our results demonstrated that DATS prevented ethanol-induced injury, as indicated by the reduced activities of aspartate transaminase (AST) and alanine aminotransferase (ALT) in the serum and culture medium, and inhibition of cell apoptosis. Furthermore, DATS reduced hepatic steatosis by up-regulating the expression of peroxisome proliferator-activated receptor-alpha (PPAR-α) and down-regulating the expression of sterolregulatory element binding protein 1c(SREBP-1c). In addition, DATS alleviated ethanol-induced oxidative stress by enhancing non-enzymatic antioxidant and enzymatic antioxidants contents and by reducing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA). These data collectively revealed that DATS protected ethanol-induced liver injury by inhibiting lipid accumulation and oxidative stress.

Diallyl trisulfide protects against ethanol-induced oxidative stress and apoptosis via a hydrogen sulfide-mediated mechanism.

Garlic is one natural source of organic sulfur containing compounds and has shown promise in the treatment of chronic liver disease. Dietary garlic consumption is inversely correlated with the progression of alcoholic fatty liver (AFL), although the exact underlying mechanisms are not clear. Our previous studies also have shown that diallyl trisulfide (DATS), the primary organosulfur compound from Allium sativum L, displayed anti-lipid deposition and antioxidant properties in AFL. The aim of the present study was to clarify the underlying mechanisms. In the present study, we used the intragastric infusion model of alcohol administration and human normal liver cell line LO2 cultured with suitable ethanol to mimic the pathological condition of AFL. We showed that accumulation of intracellular reactive oxygen species (ROS) was lowered significantly by the administration of DATS, but antioxidant capacity was increased by DATS. Additionally, DATS inhibited hepatocyte apoptosis via down-regulating Bax expression and up-regulating Bcl-2 expression, and attenuated alcohol-induced caspase-dependent apoptosis. More importantly, using iodoacetamide (IAM) to block hydrogen sulfide (H2S) production from DATS, we noted that IAM abolished all the above effects of DATS in ethanol-treated LO2 cells. Lastly, we found DATS could increase the expressions of cystathionine gamma-lyase (CSE) and cystathionine beta-synthase (CBS), the major H2S-producing enzymes. These results demonstrate that DATS protect against alcohol-induced fatty liver via a H2S-mediated mechanism. Therefore, targeting H2S may play a therapeutic role for AFL.