Aim: Aflatoxin B1 (AFB1) is hepatotoxic. Numerous studies have shown that mitochondria play an essential role in AFB1-induced steatosis. However, the mechanisms of AFB1-induced steatosis via mitochondria are still obscure. The present study aimed to confirm that AFB1 causes hepatocyte steatosis regulated by cyclooxygenase-2 (COX-2)-induced mitophagy, both in vivo and in vitro. Methods: Adult male C57BL/6 mice were randomly divided into control group with the same volume of peanut oil and exposure group administered 0.6 mg/kg AFB1 once in 2 days for 1 month. HepG2 and Cas9-PTGS2 cells were treated with 5 μM AFB1 for 48 hours. Then, various indicators were evaluated. Results: Aflatoxin B1 causes liver injury and steatosis with increased alanine aminotransferase, aspartate aminotransferase, total cholesterol, total triglyceride levels in vivo and in vitro, and elevated lipid droplets in HepG2 cells. Cyclooxygenase-2 and mitophagy pathway were induced by AFB1 in both liver tissues and cultured HepG2 cells. Further studies have shown that knockout of COX-2 with the CRISPR/Cas9 system inhibited the AFB1-induced mitophagy and steatosis in HepG2 cells. Also, the inhibition of PTEN-induced putative kinase with RNA interference attenuated the AFB1-induced steatosis. Conclusions: The results of the current study suggested that AFB1 increases the expression of COX-2, which, in turn, elevates the level of mitophagy, thereby disrupting the normal mitochondrial lipid metabolism and causing steatosis. Thus, this study implies that COX-2 may be a potential target for therapy against AFB1-induced steatosis.
1 January 2021 in Canadian Journal of Gastroenterology and Hepatology
Background and Aims. Simethicone (SIM), as an antifoaming agent, has been shown to improve bowel preparation during colonoscopy. However, the optimal timing of SIM addition remained undetermined. We aimed to investigate the optimal timing of SIM addition to polyethylene glycol (PEG) to improve bowel preparation. Methods. Eligible patients were randomly assigned to two groups: the SIM evening group (SIM addition to PEG in the evening of the day prior to colonoscopy) and the SIM morning group (SIM addition to PEG in the morning of colonoscopy). The primary outcome was Bubble Scale (BS). The secondary outcomes were Boston Bowel Preparation Scale (BBPS) and adenoma detection rate (ADR). Results. A total of 419 patients were enrolled in this study. The baseline characteristics of the patients were similar in both groups. No significant differences were observed in terms of BS (8.76 ± 0.90 vs. 8.65 ± 1.16, P = 0.81), ADR (34.1% vs. 30.8%, P = 0.47), Boston Bowel Preparation Scale (BBPS) (8.59 ± 0.94 vs. 8.45 ± 1.00, P = 0.15), and withdrawal time (8.22 ± 2.04 vs. 8.01 ± 2.51, P = 0.094) between the two groups. Moreover, safety and compliance were similar in both groups. However, the SIM evening group was associated with shorter cecal intubation time (3.80 ± 1.81 vs. 4.42 ± 2.03, P < 0.001), higher BS (2.95 ± 0.26 vs. 2.88 ± 0.38, P = 0.04) in the right colon, and diminutive ADR (62.5% vs. 38.6%, P = 0.022) in the right colon, when compared to the SIM evening group. Conclusions. The SIM addition to PEG in the evening of the day prior to colonoscopy can shorten cecal intubation time and improve BS scores and diminutive ADR of the right colon compared with the SIM addition to PEG in the morning of colonoscopy in bowel preparation.
6 September 2022 in Canadian Journal of Gastroenterology and Hepatology
Background and Aim. Obesity has been linked to incomplete colonoscopy. In the present study, we aimed to determine whether an abdominal compression bandage could improve the complete colonoscopy rate (CCR) of obese patients. Methods. Eligible patients were randomly allocated into the abdominal bandage and conventional groups during a routine colonoscopy. The primary outcome was CCR. Results. A total of 250 eligible patients were randomly assigned to the abdominal bandage and conventional groups from January 2021 to April 2021. Eleven patients (five in the abdominal bandage group and six in the conventional group) were excluded due to schedule cancellation after randomization, and 239 patients were eventually included in the final analysis. There were no significant differences between the two groups regarding baseline characteristics (P>0.05). Furthermore, no significant differences were observed in terms of advanced adenoma detection rate (AADR), polyp detection rate (PDR), bowel preparation scale (BBPS), bubble scale (BS), and withdrawal time between the two groups (P>0.05). However, compared with the conventional group, the cecal insertion time (CIT) of the abdominal bandage group was significantly shortened (279.00 (234.50305.75) vs. 421.00 (327.00485.00), P<0.001), and the CCR (96.7 vs. 88.2, P=0.01) and adenoma detection rate (ADR) (47.5 vs. 32.8, P<0.001) were improved. Besides, logistic regression analysis showed that body mass index (BMI) and abdominal compression bandage were associated with CCR. Conclusions. Abdominal compression bandages could effectively shorten CIT and improve CCR and ADR for obese patients during a routine colonoscopy. This trial is registered with the Chinese Clinical Trial Registry (No. ChiCTR2100043556).
1 February 2021 in Cancer Biotherapy and Radiopharmaceuticals
Background: Various types of tumors are likely to acquire drug resistance over time. Hence, the development of novel therapies to overcome drug resistance is critical. Studies have demonstrated that drug resistance is closely associated with the dynamic regulation of mitochondria in tumor cells. The dynamin-related protein 1 (Drp1) is involved in the regulation of mitochondrial fission and plays an important role in maintaining mitochondrial morphology, function, and distribution. It is a key protein in mitochondrial quality control. Drp1 is a GTPase localized to the cytoplasm and is a potential target in cancer therapy. A variety of drugs targeting Drp1 have shown great promise in reducing the viability and proliferation of cancer cells. The dynamic regulation of Drp1-mediated mitochondria is closely associated with tumor development, and treatment. Aim: In this article, the authors reviewed the occurrence and progression of mitochondrial fission regulated by Drp1, and its influence on cell cycle, autophagy, apoptosis, migration, invasion, the molecular mechanism of tumor stemness, and metabolic reprogramming. Targeted inhibition of Drp1 and mitochondrial fission could reduce or prevent tumor occurrence and progression in a variety of cancers. Drp1 inhibitors could reduce tumor stemness and enhance tumor sensitivity to chemotherapeutic drugs. Conclusion: Research into identifying compounds that could specifically target Drp1 will be valuable for overcoming drug resistance in tumors.
8 July 2025 in Frontiers in Cell and Developmental Biology
Liver cancer, the advanced stage of various chronic liver diseases, has garnered attention due to its high incidence and insidious progression. Lipid droplets (LDs), unique lipid storage organelles in hepatocytes, play a pivotal role in lipid metabolism. Lipophagy, a selective autophagy process initially identified in hepatocytes, regulates lipid homeostasis by selectively degrading LDs. This process offers a novel therapeutic avenue for addressing lipid metabolism disorders in liver cancer. This review highlights the regulatory role of lipophagy in liver cancer progression and its therapeutic potential. It elaborates on the molecular mechanisms underlying lipophagy-mediated LDs degradation and discusses the dual regulatory role of lipophagy in liver cancer. While lipophagy can suppress liver cancer development, under specific conditions, it may promote cancer cell proliferation, inhibit apoptosis, facilitate invasion and metastasis, and contribute to treatment resistance. Consequently, strategies targeting lipophagy for liver cancer prevention and therapy hold significant promise. These include interventions through traditional Chinese and Western medicine, as well as lifestyle modifications. This review evaluates current research, hotspots, and controversies in the field, aiming to provide innovative therapeutic strategies for liver cancer associated with abnormal lipid metabolism.
27 February 2025 in American Journal of Gastroenterology
INTRODUCTION: Conclusions regarding the suction techniques of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) remain controversial. This study aimed to compare the diagnostic accuracy of the dry suction vs wet suction technique in solid pancreatic lesions (SPLs) and determine the optimal number of passes for EUS-FNB. METHODS: This investigation was conducted as a multicenter, randomized, controlled, noninferiority trial. Patients with SPLs were randomly allocated to receive either the dry or wet suction technique. The primary outcome was diagnostic accuracy. The secondary outcomes included sensitivity, specificity, optimal number of needle passes, specimen quality, procedure time, and adverse events. RESULTS: Of the 200 patients, 193 were included in the final analysis, with 96 in the dry suction group and 97 in the wet suction group. The diagnostic accuracies were 97.92% and 96.91% in the dry and wet groups, respectively, with a 1.01% difference between the study groups (2-sided 95% CI, −3.47% to 5.48%, P = 0.659). The overall adverse event rate was 2.6%. No significant differences were observed in sample adequacy (98.9% vs 98.9%, P = 1) or blood contamination ( P = 0.796). Regarding procedure time, there was no statistical difference (18.68 ± 8.03 minutes vs 19.36 ± 8.89 minutes, P = 0.626); however, more procedural steps were required in the wet suction technique. No significant difference was found between the cumulative diagnostic accuracy of each needle (first pass 93.78% vs second pass 95.34% vs third pass 97.41%, P = 0.225). DISCUSSION: The dry suction technique is noninferior to the wet suction technique for EUS-FNB in SPLs. In the absence of rapid on-site evaluation, only one pass was required to achieve more than 90% diagnostic accuracy (ClinicalTrial.gov number NCT05549856).