作者: Mersal, Ezat A. ; El-neanaey, Amira Afifi ; Negm, Amr ; Okaz, Raghda Sobhy ; Kamel, Maher Abd El Naby ; El Sayed, Ibrahim El Tantawy ; Beshara, Nermine ; Almuraikhi, Nihal ; Abdo Ismail, Abd El-Hamid ; Khadr, Abada El Sayed ; Darwish, Wael Sobhy ; Abd Eldaim, Mabrouk Attia ; Bahr, Mohamed Hamdy ; Shawky, Tamer Mohamed

Background:Liver fibrosis represents a serious risk to global health by impairing quality of life and elevating the chances of hepatocellular carcinoma, while the intricate role of autophagy can either alleviate or worsen fibrosis depending on its functioning.Objective:Herein, we aimed to investigate the therapeutic effect of chlorogenic acid in CCl4-induced hepatic fibrosis and explored the autophagy pathway as the possible molecular target of chlorogenic acid.Methods:Rats were injected with carbon tetrachloride (1ml/kg) to induce liver fibrosis for 10 weeks. In the current study, the liver fibrosis rats were treated daily with chlorogenic acid (20, 40, and 60 mg/kg) for 30 days. Liver function tests, renal function tests, lipid peroxidation, antioxidant enzyme, anti-inflammatory NF-κB level, and autophagy pathway parameters (PI3K, AKT, mTOR, LC3, and Beclin-1) were assessed.Results:CCl4 elevated serum AST and ALT activity, and hepatic malondialdehyde, PI3K, AKT, and mTOR expressions. It decreased LC3, Beclin-1 expression, and hepatic glutathione level. The results indicated that chlorogenic acid treatment ameliorated the hepatic functions. It declined serum AST and ALT activities, improved hepatic GSH concentration, decreased lipid peroxidation, and downregulated PI3K, AKT, and mTOR protein expressions in hepatic tissue. Moreover, chlorogenic acid increased the hepatic expression of LC3 and Beclin-1. It also significantly decreased NF-kB expression.Conclusion:Chlorogenic acid showed promise in reducing liver damage in rats caused by CCl4 by influencing the autophagy process and adjusting levels of antioxidant and inflammatory markers.

2025-06-01·Cytokine

ADAM17/ACE2 interaction mediates cadmium-induced brain damage and neuroinflammation in Wistar rats

Article

作者: Abdel All, Marwa Omar ; Abdelmenem, Alshaymaa M ; Mahdi, Norah ; Salim, Mohamed S ; Alanazi, Atheer ; Mersal, Ezat A ; Morsi, Ahmed A ; Dawood, Amal F

Angiotensin-converting enzyme 2 (ACE2) is a critical component in the renin-angiotensin system. A Disintegrin And Metalloprotease 17 (ADAM17) is the first identified sheddase for common inflammatory cytokines. Changes in ACE2 expression and its biological activity facilitated by ADAM17 are involved in several diseases including neurodegenerative disorders. Herein, the study investigated an innovative viewpoint on cadmium (Cd)-induced neurotoxicity and explored whether ADAM17/ACE2 interplay mediated the Cd-induced brain injury and neuroinflammation. For this aim, 32 adult male Wistar rats were included and randomly grouped. Eight rats served as a control group and the remaining 24 experimental rats were exposed to Cd (5 mg/kg/day, orally, 21 days); assigned as either Cd-alone (Cd group), received ADAM17 inhibitor [TAPI-1, 10 mg/kg, intraperitoneal] (Cd/TAPI-1 group), or received vitamin E, 100 mg/kg/d, orally (Cd/vit E group). Ultimately, the brains were harvested and exposed to biochemical, histological, and immunohistochemical (IHC) studies for measuring oxidative stress and inflammatory markers, histopathological examination, and for IHC identification of ADAM17, ACE2, and glial fibrillary acidic protein (GFAP). Cd resulted in biochemical disturbances in the inflammatory and oxidative stress markers, degenerative histopathological changes in the cerebral cortex and hippocampus, and enhanced ADAM17 and GFAP expression, meanwhile downregulated ACE2 expression. Vitamin E showed a superior effect in maintaining the oxidative/antioxidant-balanced defense system. However, the biochemical and histological changes in the brain were more effectively alleviated by TAPI-1 administration than by the partial improvement made by vitamin E therapy. These observations suggested that oxidative stress was involved in Cd-mediated upregulation of ADAM17 and ACE2 shedding. It was concluded that oxidative stress, at least in part, resulted in ADAM17-mediated ACE2 cleavage in the current Cd-induced brain damage.

2025-04-01·Annals of Medicine & Surgery

Exploring the evolution of evidence synthesis: a bibliometric analysis of umbrella reviews in medicine

Review

作者: Hassanipour, Soheil ; Hashemi, Mohammad ; Naeiji, Mahdi ; Sadeghi Douki, Seyed Amir Hossein ; Keivanlou, Mohammad-Hossein ; Nayak, Sandeep Samethadka ; Faraji, Niloofar ; Amini-Salehi, Ehsan ; Fleischman, Micah ; Ulrich, Michael T. ; Alotaibi, Abdolhadi ; Sahli, Yasmin ; Patel, Masum ; Maghsoodifar, Hasan

Background:Umbrella review studies have become increasingly vital in evidence synthesis, offering a comprehensive overview by analyzing multiple systematic reviews and meta-analyses. This bibliometric study aimed to delineate the growth and thematic evolution of umbrella reviews within evidence-based medicine, illuminating their integral role in synthesizing high-level evidence.Methods:Utilizing the Web of Science Core Collection, we performed a search for publications on umbrella reviews, identifying relevant articles through a refined strategy. Analytical tools including VOS Viewer and CiteSpace were employed to visualize connections and trends among the gathered data, converting intricate bibliometric information into comprehensible visual maps.Results:Our search yielded 2965 pertinent publications, highlighting a marked growth in research output, particularly from 2010 to 2023. The United States, United Kingdom, and China were predominant in this field, with leading institutions like King’s College London and the University of Toronto at the forefront. The analysis identified major journals such as BMJ Open and PLOS One as key publishers. Co-citation and keyword analysis revealed current research focuses, with recent trends emphasizing COVID-19 and mental health. The study also uncovered a robust international collaboration network, underscoring the global impact of umbrella reviews.Conclusion:This bibliometric analysis confirms the expanding influence and utility of umbrella reviews in medical research and decision-making. By charting the evolution and current trends in this field, our study not only showcases the geographical and institutional distribution of research but also guides future scholarly efforts to advance evidence synthesis methodologies.

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