Effects of Thalidomide on the Expression of Adhesion Molecules in Rat Liver Cirrhosis

This study was to evaluate the effects of thalidomide on expression of adhesion molecules in liver cirrhosis. The cirrhosis was induced in Wistar rats by intraperitoneal injection of CCl(4), and thalidomide (10 mg/kg/day or 100 mg/kg/day) was given by intragastric administration for 8 weeks. Liver histopathology and immunohistochemistry were significantly improved and the expressions of ICAM-1, VCAM-1, E-selectin, and TNF-α mRNA and protein were decreased significantly in rats treated with a high dose of thalidomide. Close positive correlation was observed in the expression of the TNF-α mRNA and that of ICAM-1, VCAM-1, and E-selectin mRNA, respectively. These results indicate that thalidomide exerts its effect on the downregulation of adhesion molecules via TNF-α signaling pathway to inhibit liver fibrosis

miR-200a attenuated oxidative stress, inflammation, and apoptosis in dextran sulfate sodium-induced colitis through activation of Nrf2

IntroductionOxidative stress and inflammatory responses are critical factors in ulcerative colitis disease pathogenesis. Nuclear factor erythroid 2-related factor 2 (Nrf2) modulates oxidative stress and suppresses inflammatory responses, and the protective benefits of Nrf2 activation have been associated with the therapy of ulcerative colitis. MicroRNA-200a (miR-200a) could target Kelch-like ECH-associated protein 1 (Keap1) and activate the Nrf2-regulated antioxidant pathway. Nevertheless, whether miR-200a modulates the Keap1/Nrf2 pathway in dextran sulfate sodium (DSS)-induced colonic damage is unknown. Here, our research intends to examine the impact of miR-200a in the model of DSS-induced colitis.MethodsPrior to DSS intervention, we overexpressed miR-200a in mice for four weeks using an adeno-associated viral (AAV) vector to address this problem. ELISA detected the concentration of inflammation-related cytokines. The genes involved in inflammatory reactions and oxidative stress were identified using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blot, and immunofluorescence. Moreover, we applied siRNAs to weakened Nrf2 expression to confirm the hypothesis that miR-200a provided protection via Nrf2.ResultsThe present study discovered miR-200a down-regulation, excessive inflammatory activation, enterocyte apoptosis, colonic dysfunction, and Keap1/Nrf2 antioxidant pathway inactivation in mouse colitis and NCM460 cells under DSS induction. However, our data demonstrated that miR-200a overexpression represses Keap1 and activates the Nrf2 antioxidant pathway, thereby alleviating these adverse alterations in animal and cellular models. Significantly, following Nrf2 deficiency, we failed to observe the protective benefits of miR-200a against colonic damage.DiscussionTaken together, through activating the Keap1/Nrf2 signaling pathway, miR-200a protected against DSS-induced colonic damage. These studies offer an innovative therapeutic approach for ulcerative colitis

The role of Nrf2 in the pathogenesis and treatment of ulcerative colitis

Ulcerative colitis (UC) is a chronic inflammatory bowel disease involving mainly the colorectal mucosa and submucosa, the incidence of which has been on the rise in recent years. Nuclear factor erythroid 2-related factor 2 (Nrf2), known for its key function as a transcription factor, is pivotal in inducing antioxidant stress and regulating inflammatory responses. Numerous investigations have demonstrated the involvement of the Nrf2 pathway in maintaining the development and normal function of the intestine, the development of UC, and UC-related intestinal fibrosis and carcinogenesis; meanwhile, therapeutic agents targeting the Nrf2 pathway have been widely investigated. This paper reviews the research progress of the Nrf2 signaling pathway in UC

Research hotspots and trend analysis of abdominal pain in inflammatory bowel disease: a bibliometric and visualized analysis

Aims: The study aimed to provide a bibliometric and visual analysis of research on abdominal pain in inflammatory bowel disease and discuss the current status, research hotspots, and future developments.Methods: We used the Web of Science Core Collection to comprehensively search the literature on abdominal pain-related research in IBD published between 2003 and 2022. The bibliometric and visual analysis was performed through CiteSpace, VOSviewer software, R language, and the bibliometric online analysis platform, including authors, institutions, countries, journals, references, and keywords in the literature.Results: A total of 3,503 relevant articles are included, indicating that the number of articles in this field has increased in recent years. The United States leads the way with a dominant position in terms of article output, followed by China and JAPAN. United States (967 articles), University of Calgary (98 articles), and World Journal of Gastroenterology (127 articles) are the top publishing countries, institutions, and journals, respectively; keyword analysis shows that gut microbiota, depression, stress, visceral hypersensitivity, and multidisciplinary approach are the hot spots and trends in this research area.Conclusion: Abdominal pain-related studies in IBD have received increasing attention in the past two decades. This study provides the first bibliometric analysis of papers in this research area using visualization software and data information mining. It provides insights into this field’s current status, hot spots, and trends. However, many outstanding issues in this research area still need further exploration to provide a theoretical basis for its clinical application

Discovery of Endothelium and Mesenchymal Properties of Primo Vessels in the Mesentery

Recent evidences demonstrated that endothelial-to-mesenchymal transition (EndMT) has a crucial role in cancer and is recognized as a unique source of cancer-associated fibroblasts (CAFs). Primo vascular system (PVS) is a new circulatory system which may play an important role in cancer metastasis and regeneration. In the current study, we applied previously established time-saving method to identify primo vessels and further investigated the immunocytochemical properties of primo vessels. Both primo vessels and primary primo vessel cells in the mesentery expressed endothelial markers and fibroblast markers. Double-labeling experiments demonstrated that endothelial and fibroblast markers are coexpressed in primo vessels. In addition, under the stimulation of TGF-β1 in vitro, primary primo vessel cells differentiated into fibroblasts. Therefore, we found that primo vessels in the mesentery had a transitional structure between endothelium and mesenchymal. This is a new finding of EndMT in normal postnatal animals

Plasma Hormones Facilitated the Hypermotility of the Colon in a Chronic Stress Rat Model

Objective: To study the relationship between brain-gut peptides, gastrointestinal hormones and altered motility in a rat model of repetitive water avoidance stress (WAS), which mimics the irritable bowel syndrome (IBS). Methods: Male Wistar rats were submitted daily to 1-h of water avoidance stress (WAS) or sham WAS (SWAS) for 10 consecutive days. Plasma hormones were determined using Enzyme Immunoassay Kits. Proximal colonic smooth muscle (PCSM) contractions were studied in an organ bath system. PCSM cells were isolated by enzymatic digestion and IKv and IBKca were recorded by the patch-clamp technique. Results: The number of fecal pellets during 1 h of acute restraint stress and the plasma hormones levels of substance P (SP), thyrotropin-releasing hormone (TRH), motilin (MTL), and cholecystokinin (CCK) in WAS rats were significantly increased compared with SWAS rats, whereas vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP) and corticotropin releasing hormone (CRH) in WAS rats were not significantly changed and peptide YY (PYY) in WAS rats was significantly decreased. Likewise, the amplitudes of spontaneous contractions of PCSM in WAS rats were significantly increased comparing with SWAS rats. The plasma of WAS rats (100 ml) decreased the amplitude of spontaneous contractions of controls. The IKv and IBKCa of PCSMs were significantly decreased in WAS rats compared with SWAS rats and the plasma of WAS rats (100 ml) increased the amplitude of IKv and IBKCa in normal rats

Jejunal Ulcer Caused by Schistosoma japonicum

Intestinal schistosomiasis can be caused by the trematodes Schistosoma japonicum that mainly exists in East Asia or the S. mansoni in Africa and South America. The adult worms of S. japonicum live in the mesenteric veins and excrete eggs that circulate to the liver and colon; the eggs migrate through the intestinal wall and pass out with the stool. Here, we report a case of jejunal ulcer caused by the infection of Schistosoma japonicum. A 63-year-old woman from Wuhan, China, was admitted with left quadrant abdominal pain and weight loss for more than 6 months. The patient’s computerized tomography reported cirrhotic liver changes, jejunal wall edema, and narrowed lumen; the upper enteroscopy corroborated these findings with the presence of several jejunal ulcers and edema. The pathology report showed chronic inflammation with ulcerative changes and S. japonicum eggs deposition. Schistosomiasis is one of the neglected tropical diseases that affect the poorest. Although a great improvement has been made to control it, there is a lot of work that remains to be fulfilled

Research on Inner Gas Inflation Improvements in Double-layer Gas-assisted Extrusion of Micro-tubes

Micro-tubes have small diameters and thin wall thicknesses. When using double-layer gas-assisted extrusion (DGAE) technology to process micro-tubes, due to the influence of flow resistance, airflow from the inner gas-assisted layer cannot flow into the atmosphere through the lumen. Over time, it will inflate or even fracture the micro-tubes intermittently and periodically. To solve this problem, a new double-layer micro-tube gas-assisted extrusion die was designed in this study. Its mandrel has an independent airway leading to the lumen of the extrudate, with which the gas flow into the lumen of the extrudate can be regulated by employing forced exhaust. Using the new die, we carried out extrusion experiments and numerical calculations. The results show a significant positive correlation between micro-tube deformation and gas flow rate in the lumen of a micro-tube. Without considering the refrigerant distortion of the microtube, the flow rate of forced exhaust should be set equal to that of the gas from the inner gas-assisted layer flow into the micro-tube lumen. By doing this, the problem of the micro-tube being inflated can be eliminated without causing other problems

Preparation of Microporous Silicone Rubber Membrane with Tunable Pore Size via Solvent Evaporation-Induced Phase Separation

Silicone rubber membrane with ordered micropores in the surface was prepared by means of the solvent evaporation-induced phase separation. A ternary solution including liquid silicone rubber precursor, liquid paraffin, and hexane was cast to form a film with a two-phase structure after the hexane was evaporated. The micropores were generated by removing liquid paraffin phase in the cured silicone rubber film. The effects of the liquid paraffin concentration, casting temperature, initial casting solution thickness, air circulation, and addition of surfactant Span-80 on the pore structure in the membrane surface were investigated. The average pore size increases with increasing liquid paraffin concentration or the initial casting solution thickness. The formation of pore structure in the membrane surface is related to the phase separation and thus the phase separation process of the casting solution surface was in situ observed using the digital microscope. The formation mechanism of pore is attributed to a nucleation, growth, and coalescence process of liquid paraffin phase in the membrane surface