Research Progress on the Mechanism of Acute Hypertriglyceridemic Pancreatitis.

ABSTRACT: The incidence rate of hypertriglyceridemia pancreatitis (HTGP) has experienced a notable increase in recent years, with eclipsing alcohol as the second leading cause of acute pancreatitis (AP). HTGP is often associated with more severe local and systemic complications. Recognized as a metabolic disorder hypertriglyceridemia (HTG), it holds significant relevance in the pathogenesis of HTGP, yet its mechanisms are not fully understood. Both primary (genetic) and secondary (acquired) factors contribute to elevated triglyceride (TG) levels, which concurrently influence the progression of HTGP. This article presents a comprehensive review of the evolving research on HTGP pathogenesis, encompassing lipid synthesis and metabolism, calcium signal transduction, inflammatory mediators, endoplasmic reticulum stress, autophagy, mitochondrial injury by fatty acids, oxidative stress response, genetic factors, and gene mutations. By unraveling the intricate mechanisms underlying HTGP, this article aims to enhance physicians' understanding of the disease and facilitate the development of potential targeted pharmacological interventions for patients.

Dry suction versus wet suction technique of endoscopic ultrasound-guided fine-needle biopsy for diagnosis of solid pancreatic lesions: study protocol of a multicenter randomized controlled non-inferiority trial.

BACKGROUND: Studies have shown that the wet suction technique in endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) generates better histological diagnostic accuracy and specimen quality than the dry suction technique. However, conclusions of wet suction on the diagnostic accuracy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) are still controversial. Besides, the optimal number of passes for EUS-FNB has not been determined. We aimed to design a large multicenter randomized trial to compare the diagnostic accuracy of dry suction versus wet suction technique in solid pancreatic lesions (SPLs) using 22G Franseen needles and determine the optimal number of passes required for EUS-FNB. METHODS: This is a multi-center open-label, randomized controlled non-inferiority trial with two parallel groups. Two hundred patients with SPLs will undergo EUS-FNB using 22G Franseen needles in 4 tertiary hospitals in China and will be randomly assigned to the dry suction group and wet suction group in a ratio of 1:1. The primary endpoint is diagnostic accuracy. Secondary endpoints include the optimal number of needle passes, sensitivity, specificity, specimen quality, cytological diagnoses, time of the procedure, and incidence of complications. DISCUSSION: This study has been designed to determine (i) whether EUS-FNB using 22G Franseen needle with dry suction is non-inferior to wet suction in terms of diagnostic accuracy and (ii) the optimal number of passes during EUS-FNB of SPLs using 22G Franseen needle. TRIAL REGISTRATION: ClinicalTrials.gov NCT05549856. Registered on September 22, 2022.

Ferroptosis inhibition attenuates inflammatory response in mice with acute hypertriglyceridemic pancreatitis.

BACKGROUND: Ferroptosis is involved in developing inflammatory diseases; yet, its role in acute hypertriglyceridemic pancreatitis (HTGP) remains unclear. AIM: To explore whether ferroptosis is involved in the process of HTGP and elucidate its potential mechanisms. METHODS: An HTGP mouse model was induced using intraperitoneal injection of P-407 and caerulein (CAE). Then, pancreatic tissues from the model animals were subjected to proteome sequencing analysis. The pathological changes and scores of the pancreas, lung, and kidney were determined using hematoxylin-eosin staining. The levels of serum amylase (AMY), triglyceride, and total cholesterol were measured with an automatic blood cell analyzer. Additionally, the serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß were determined by enzyme linked immunosorbent assay. Malonaldehyde (MDA), glutathione (GSH), and Fe2+ were detected in the pancreas. Finally, immunohistochemistry was performed to assess the expression of ferroptosis-related proteins. RESULTS: Proteome sequencing revealed that ferroptosis was involved in the process of HTGP and that NADPH oxidase (NOX) 2 may participate in ferroptosis regulation. Moreover, the levels of serum AMY, TNF-α, IL-6, and IL-1ß were significantly increased, MDA and Fe2+ were upregulated, GSH and ferroptosis-related proteins were reduced, and the injury of the pancreas, lung, and kidney were aggravated in the P407 + CAE group compared to CAE and wild type groups (all P < 0.05). Notably, the inhibition of ferroptosis and NOX2 attenuated the pathological damage and the release of TNF-α, IL-6, and IL-1ß in the serum of the mice. CONCLUSION: Ferroptosis was found to have an important role in HTGP and may be considered a potential target for clinical treatment.

Impact of an Abdominal Compression Bandage on the Completion of Colonoscopy for Obese Adults: A Prospective Randomized Controlled Trial.

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 (234.50-305.75) vs. 421.00 (327.00-485.00), 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).

Optimal Timing of Simethicone Supplement for Bowel Preparation: A Prospective Randomized Controlled Trial.

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.

The Regulatory Mechanisms of Dynamin-Related Protein 1 in Tumor Development and Therapy.

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.

Aflatoxin B1-Induced COX-2 Expression Promotes Mitophagy and Contributes to Lipid Accumulation in Hepatocytes In Vitro and In Vivo.

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.

Effects of Tec Tyrosine Kinase Inhibition on the Inflammatory Response of Severe Acute Pancreatitis-Associated Acute Lung Injury in Mice.

BACKGROUND: The Tec kinase family is involved in acute and chronic inflammatory diseases, but its relationship with severe acute pancreatitis (SAP) remains unclear. AIMS: To investigate whether Tec tyrosine kinase can be used as a target for severe acute pancreatitis-associated acute lung injury (PALI). METHODS: A total of 90 mice were randomly assigned into four groups: SAP (n = 15), control (n = 15), SAP + α-cyano-ß-hydroxy-ß-methyl-N-(2,5-dibromophenyl)propenamide (LFM-A13) (pretreated with Tec kinase inhibitor LFM-A13, n = 15), and SAP + Tec siRNA (pretreated with PBS/negative control siRNA/Tec siRNA, n = 45). SAP was induced by caerulein and lipopolysaccharide. Animals were sacrificed at 0, 3, 24, 48, and 72 h, respectively. Pathological changes and scores of the lung and pancreas were determined using hematoxylin-eosin staining. Expression of Tec and phosphorylated Tec (p-Tec) were examined by real-time polymerase chain reaction, Western blot, and immunoprecipitation. Serum levels of amylase, myeloperoxidase, and pro-inflammatory cytokines were measured by ELISA. RESULTS: The expression of Tec in lung tissue was significantly higher in the SAP group than in the control group (p < 0.05), and p-Tec expression gradually increased with time. Furthermore, p-Tec expression was significantly lower in the SAP + LFM-A13 group than in the SAP group (p < 0.05); however, Tec expression did not vary. Tec inhibitors, LFM-A13 and Tec siRNA, alleviated pathological damage and release of inflammatory cytokines (p < 0.05). CONCLUSIONS: Tec tyrosine kinase plays a key role in PALI, and is therefore a potential target for clinical treatment.