This research in vivo assessed the impact of the ethanolic extract of Annona muricata (A. muricata) on the histopathology, immunohistochemistry, and biochemistry of thioacetamide (TAA)-induced liver cirrhosis in Sprague Dawley rats. The rats, gavaged precisely with two doses of A. muricata (250 mg/kg and 500 mg/kg) with TAA, presented a substantial reduction in the liver index and hepatocyte propagation, with much lower cell injury. These groups showed meaningfully down-regulated proliferating cell nuclear antigen (PCNA) in the liver and spleen, α-smooth muscle actin (α-SMA), and transforming growth factor-beta 1 (TGF-β1) in liver parenchymal tissue. The liver homogenate displayed enhanced antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT) activity, along with a decrease in malondialdehyde (MDA) levels. The serum levels of bilirubin, total protein, albumin, and liver enzymes alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were returned to normal and were similar to that of the normal control and silymarin with TAA-treated groups. Oral acute toxicity revealed no evidence of any toxic symbols or mortality in rats, indicating the safety of A. muricata. Therefore, the normal microanatomy of hepatocytes, the clampdown of PCNA, α-SMA, TGF-β, improved antioxidant enzymes (SOD and CAT), and condensed MDA with repairs of liver biomarkers validate the hepatoprotective effect of A. muricata.

/pdf/histopathological-evaluation-of-annona-muricata-in-taa-12kvcglc.pdf

Histopathological Evaluation of Annona muricata in TAA-Induced Liver Injury in Rats

Hepatic ischemia-reperfusion (IR) injury is a clinically significant process that frequently occurs in liver transplantation, partial hepatectomy, and hemorrhagic shock. The aim of this study was to explore the effectiveness of luteolin in hepatic IR injury and the underlying mechanism. BALB/c mice were randomly divided into six groups, including normal controls (NC), luteolin (50 mg/kg), sham procedure, IR+25 mg/kg luteolin, and IR+50 mg/kg luteolin group. Serum and tissue samples were collected at 6 and 24 h after reperfusion to assay liver enzymes, inflammatory factors, expression of proteins associated with apoptosis and autophagy, and factors associated with the extracellular signal-regulated kinase/peroxisome proliferator-activated receptor alpha (ERK/PPARα) pathway. Luteolin preconditioning decreased hepatocyte injury caused by ischemia-reperfusion, downregulated inflammatory factors, and inhibited apoptosis and autophagy. Luteolin also inhibited ERK phosphorylation and activated PPARα.

https://downloads.hindawi.com/journals/ppar/2022/8161946.pdf

Luteolin Pretreatment Attenuates Hepatic Ischemia-Reperfusion Injury in Mice by Inhibiting Inflammation, Autophagy, and Apoptosis via the ERK/PPARα Pathway

Previous studies have reported that glucagon-like peptide-1 (GLP-1) may play a critical role in the development of intestinal ischemia-reperfusion (I/R) injury. The present study aimed to investigate whether liraglutide (GLP-1 analog) protects against intestinal I/R injury and reveals the possible underlying mechanism.Temporary superior mesenteric artery occlusion was performed to establish an intestinal I/R injury mouse model. Different doses of liraglutide were administered in vivo. Then, the survival rate of mice exposed to different ischemia times, the histopathology, intestinal barrier index, cytokine production, intestinal tissue apoptosis, and the levels of several proteins were detected in each group.Pretreatment with liraglutide significantly alleviated the pathological changes induced by I/R and increased the overall survival of mice exposed to intestinal I/R injury. Moreover, liraglutide attenuated neutrophil infiltration of intestinal tissues, pro-inflammatory cytokine production (including IL-1β, IL-6, and TNF-α), and apoptosis of intestinal tissues caused by intestinal I/R injury. In addition, liraglutide inhibited the nuclear translocation of nuclear factor-κB (NF-κB) and up-regulated the phosphorylation levels of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) in the I/R group.Liraglutide may attenuate the inflammatory response and the apoptosis of intestinal tissues via the NF-κB and PI3K/Akt pathway, protecting against intestinal I/R. 

Liraglutide attenuates intestinal ischemia/reperfusion injury via NF-κB and PI3K/Akt pathways in mice.

Onosma species (Boraginaceae) are well known as medicinal plants due to their wide range of pharmaceutical potential. The present study aims to investigate the anticancer (in vitro) and chemo-protective (in vivo) efficacies of Onosma mutabilis extract (OME) in the azoxymethane (AOM)-induced aberrant crypt foci (ACF) in rats. The in vitro antiproliferative effects of OME were determined on two human tumor cell lines (Caco-2 and HT-29) via MTT assay. The in vivo chemoprotective effects of OME were investigated by performing various biochemical analyses in serum and tissue homogenates of albino rats, along with determining oxidative stress biomarkers. Inflammatory biomarkers of colon, colonic gross morphology (by methylene blue), ACF formation, and colonic histopathology (H & E stain) were determined. The immunohistochemistry of colonic tissues was also assessed by Bax and Bcl-2 protein expression. The results showed that the antitumor activity of OME against Caco-2 and HT-29 colorectal cancer cells ranged between 22.28–36.55 µg/mL. OME supplementation caused a significant drop in the ACF values and improved the immunohistochemistry of the rats shown by up-regulation of Bax and down-regulation of Bcl-2 protein expressions. These outcomes reveal that O. mutabilis may have chemoprotective efficiency against AOM-induced colon cancer represented by the attenuation of ACF formation possibly through inhibition of free radicals, inflammation, and stimulation of the colon antioxidant armory (SOD, CAT, and GPx) and positive regulation of the Nrf2-Keap1 pathway.

/pdf/chemopreventive-effects-of-onosma-mutabilis-against-1gevq5mt.pdf

Chemopreventive Effects of Onosma mutabilis against Azoxymethane-Induced Colon Cancer in Rats via Amendment of Bax/Bcl-2 and NF-κB Signaling Pathways

Reactive oxygen species (ROS) are radical oxygen intermediates that serve as important second messengers in signal transduction. However, when the accumulation of these molecules exceeds the buffering capacity of antioxidant enzymes, oxidative stress and endothelial cell (EC) dysfunction occur. EC dysfunction shifts the vascular system into a pro-coagulative, proinflammatory state, thereby increasing the risk of developing cardiovascular (CV) diseases and metabolic disorders. Studies have turned to the investigation of microRNA treatment for CV risk factors, as these post-transcription regulators are known to co-regulate ROS. In this review, we will discuss ROS pathways and generation, normal endothelial cell physiology and ROS-induced dysfunction, and the current knowledge of common metabolic disorders and their connection to oxidative stress. Therapeutic strategies based on microRNAs in response to oxidative stress and microRNA’s regulatory roles in controlling ROS will also be explored. It is important to gain an in-depth comprehension of the mechanisms generating ROS and how manipulating these enzymatic byproducts can protect endothelial cell function from oxidative stress and prevent the development of vascular disorders.

https://www.mdpi.com/2073-4409/12/9/1341/pdf?version=1683529293

Oxidative Stress and MicroRNAs in Endothelial Cells under Metabolic Disorders

Liver transplantation is the ultimate method for treating end-stage liver disease. With the increasing prevalence of obesity, the number of patients with non-alcoholic fatty liver, a common cause of chronic liver disease, is on the rise and may become the main cause of liver transplantation in the future. With the increasing gap between the number of donor livers and patients waiting for liver transplantation and the increasing prevalence of non-alcoholic fatty liver, the proportion of steatosis livers among non-standard donor organs is also increasing. Ischemia-reperfusion injury has historically been the focus of attention in the liver transplantation process, and severe ischemia-reperfusion injury leads to adverse outcomes of liver transplantation. Studies have shown that the production of reactive oxygen species and subsequent oxidative stress play a key role in the pathogenesis of hepatic ischemia and reperfusion injury and non-alcoholic fatty liver. Furthermore, the sensitivity of fatty liver transplantation to ischemia-reperfusion injury has been suggested to be related to the production of reactive oxygen species (ROS) and oxidative stress. In ischemia-reperfusion injury, Kupffer cell and macrophage activation along with mitochondrial damage and the xanthine/xanthine oxidase system promote marked reactive oxygen species production and the inflammatory response and apoptosis, resulting in liver tissue injury. The increased levels of ROS and lipid peroxidation products, vicious circle of ROS and oxidative stress along with mitochondrial dysfunction promoted the progress of non-alcoholic fatty liver. In contrast to the non-fatty liver, a non-alcoholic fatty liver produces more reactive oxygen species and suffers more serious oxidative stress when subjected to ischemia-reperfusion injury. We herein review the effects of reactive oxygen species on ischemia-reperfusion injury and non-alcoholic fatty liver injury as well as highlight several treatment approaches.

/pdf/reactive-oxygen-species-induce-fatty-liver-and-ischemia-8a3i98e3.pdf

Reactive Oxygen Species Induce Fatty Liver and Ischemia-Reperfusion Injury by Promoting Inflammation and Cell Death

Clinical islet transplantation has the potential to cure type 1 diabetes. Despite recent therapeutic success, it is still uncommon because transplanted islets are damaged by multiple challenges, including instant blood mediated inflammatory reaction (IBMIR), inflammatory cytokines, hypoxia/reperfusion injury, and immune rejection. The transplantation microenvironment plays a vital role especially in intraportal islet transplantation. The identification and targeting of pathways that function as “master regulators” during deleterious inflammatory events after transplantation, and the induction of immune tolerance, are necessary to improve the survival of transplanted islets. In this article, we attempt to provide an overview of the influence of microenvironment on the survival of transplanted islets, as well as possible therapeutic targets.

The Influence of Microenvironment on Survival of Intraportal Transplanted Islets

Development and validation of LightGBM algorithm for optimizing of Helicobacter pylori antibody during the minimum living guarantee crowd based gastric cancer screening program in Taizhou, China.

Development and Validation of a Machine Learning Algorithm for the Detection of Helicobacter Pylori Antibody During the Minimum Living Guarantee Crowd Based Gastric Cancer Screening Program in Taizhou, China

Ling-ling Yan

Papers

Reactive Oxygen Species Induce Fatty Liver and Ischemia-Reperfusion Injury by Promoting Inflammation and Cell Death

The Influence of Microenvironment on Survival of Intraportal Transplanted Islets

Development and validation of LightGBM algorithm for optimizing of Helicobacter pylori antibody during the minimum living guarantee crowd based gastric cancer screening program in Taizhou, China.

Development and Validation of a Machine Learning Algorithm for the Detection of Helicobacter Pylori Antibody During the Minimum Living Guarantee Crowd Based Gastric Cancer Screening Program in Taizhou, China