Cell Biochemistry and Function最新文献

{"title":"From Redox Imbalance to Tissue Injury: Insights Into Antidepressant Drug Amitriptyline Effects on Salivary Glands","authors":"Cristian dos Santos Pereira,&nbsp;Deiweson Souza-Monteiro,&nbsp;Yago Gecy de Sousa Né,&nbsp;Jorddy Neves da Cruz,&nbsp;Vinicius Ruan Neves dos Santos,&nbsp;Everton Luiz Pompeu Varela,&nbsp;Sandro Percário,&nbsp;Leonardo Oliveira Bittencourt,&nbsp;Antonio Hernandes Chaves-Neto,&nbsp;Rafael Rodrigues Lima","doi":"10.1002/cbf.70189","DOIUrl":"10.1002/cbf.70189","url":null,"abstract":"<p>This study aimed to investigate the effects of amitriptyline administration on the salivary glands and saliva of rats. Twenty-eight male Wistar rats (60 days old) were divided into two groups (<i>n</i> = 14 per group): control and amitriptyline-treated (10 mg/kg/day for 30 days). After the treatment period, saliva samples induced by pilocarpine were collected to analyze total protein concentration, amylase activity, and antioxidant capacity, while salivary glands were harvested for assessments of oxidative stress markers and morphological changes. Amitriptyline increased total protein and decreased amylase activity in saliva, with no change in the Trolox-equivalent antioxidant capacity (TEAC). The drug triggered oxidative stress in both glands by the decrease in TEAC concentration and increased lipid peroxidation. Morphometric analysis showed that amitriptyline increased the total area of stroma and decreased the ductal area in both glands. In the submandibular gland, acinar area was reduced as well. These findings suggest that amitriptyline-salivary gland dysfunction is associated with oxidative imbalance, morphometric, and alterations in saliva composition, contributing to a broader understanding of amitriptyline's adverse effects.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12949951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Efficacy of S-Allyl-L-Cysteine an Active Constituent of Aged Garlic Extract in Rat Model of Gestational Diabetes Mellitus","authors":"Jingjing Wang,&nbsp;Liming Ma,&nbsp;Xiaofeng Yan,&nbsp;Ying Huang","doi":"10.1002/cbf.70184","DOIUrl":"10.1002/cbf.70184","url":null,"abstract":"<div>\u0000 \u0000 <p>Gestational diabetes mellitus (GDM) is a major pregnancy complication that adversely affects fetal development. Emerging evidence implicates inflammation and oxidative stress in its pathogenesis, highlighting the need for in-depth mechanistic insights. Aged garlic extract (AGE) and its active compound, S-allyl-<span>L</span>-cysteine (SAC), possess anti-inflammatory, antioxidant, and antidiabetic properties in type I and II diabetes; however, their therapeutic potential in GDM remains unknown. This study developed a rat model of GDM (<i>n</i> = 40) by administering a high-fat diet before and during pregnancy, inducing GDM with Nicotinamide, and inducing chronic stress. Glycemic parameters, insulin signaling genes (IRS-2, AKT-1, and PCK-1), glucose transporters (GLUT-2 and GLUT-4), proinflammatory cytokines, and antioxidants were assessed on gestational day 5. GDM-induced rats (<i>n</i> = 6 in each group) received different treatments, including SAC, insulin, and their combination. On day 15, significant therapeutic benefits were observed in the SAC + insulin group. The model effectively mimics human GDM by demonstrating insulin resistance and dysregulated signaling pathways. SAC treatment reduced inflammation and oxidative stress and restored insulin signaling. GDM involves inflammatory cascades and insulin signaling dysregulation, whereas SAC, particularly in combination with insulin, shows promise as a therapeutic intervention for GDM. These findings provide valuable insights for future research and the development of novel GDM treatment strategies.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147302707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophils in Coronavirus Disease 2019: Guardians or Triggers of Immunopathology?","authors":"Fatemeh Mohammadi Henjeroei,&nbsp;Niloufar Nosratabadi,&nbsp;Hossein Pourghadamyari,&nbsp;Akbar Anaeigoudari,&nbsp;Farnaz Sedghy,&nbsp;Reza Nosratabadi","doi":"10.1002/cbf.70186","DOIUrl":"10.1002/cbf.70186","url":null,"abstract":"<div>\u0000 \u0000 <p>COVID-19 (coronavirus disease 2019) is a respiratory viral disease with a wide range of clinical symptoms that emerged in December 2019. Innate immunity serves as a rapid immune system that can fight off pathogens before they can spread and cause an active infection. Neutrophils, the most abundant innate immune cells, are the first cells to migrate to the site of infection, where they defend against invading pathogens. Once activated at the inflammatory site, neutrophils mediate host protection through multiple mechanisms, including the phagocytosis of pathogens, the release of antimicrobial and pro-inflammatory enzymes, the production of reactive oxygen species (ROS), and the extrusion of their chromatin to form neutrophil extracellular traps (NETs) that bind to extracellular pathogens. Furthermore, neutrophils can move toward the source of the stimulus through a mechanism called chemotaxis, which is mediated by adhesion molecules and chemokine–chemokine receptor axes. However, neutrophil overactivation can have deleterious effects on various organs through the induction of cytokine storms, ROS production, and NET formation. Moreover, the contribution of distinct neutrophil subsets and their plasticity over the course of infection and recovery remain poorly understood. This review summarizes the current knowledge of the interplay between neutrophils and SARS-CoV-2, highlighting the most important mechanisms involved in the pathogenesis of COVID-19, to advance our understanding of this disease.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adipose Tissue Extracellular Matrix Remodeling: A Driver of Obesity and Insulin Resistance","authors":"Imane Nait Irahal,&nbsp;Asmaa Chbel,&nbsp;Ayoub Lafnoune,&nbsp;Bouchra Darkaoui,&nbsp;Hicham Wahnou","doi":"10.1002/cbf.70188","DOIUrl":"10.1002/cbf.70188","url":null,"abstract":"<div>\u0000 \u0000 <p>This review explores the role of extracellular matrix (ECM) in adipose tissue highlighting its composition, regulation, and impact on obesity and insulin resistance. The ECM in adipocytes is a dynamic entity and highly organized network composed of structural proteins which provide mechanical support for cells and tissues and regulate cellular signaling. ECM modifiers, such as matrix metalloproteinases and tissue inhibitors of metalloproteinases, coordinate ECM remodeling to allow the expansion of adipocytes. Furthermore, ECM receptors like integrins and CD44 mediate adipocytes–microenvironment interactions, affecting the inflammatory process resulting in insulin resistance. The ECM components are posttranslational being modified by an array of remodeling enzymes, such as lysyl oxidase and prolyl-4-hydroxylase, to regulate ECM integrity. While excessive ECM deposition and fibrosis urge physical constraints on adipocyte expansion, ECM remodeling emerges as a denominator linking obesity and insulin resistance associated with vascular dysfunction and severe inflammation emphasizing the role of ECM in metabolic diseases.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of the Apelin/APJ Axis Modulates Type 1 Cytotoxic T Cell and Type 2 Cytotoxic T-Related Immune Responses in an Animal Model of Metastatic Breast Cancer","authors":"Tayyebeh Tavakoli,&nbsp;Raziyeh Zandvakili,&nbsp;Javad Masoumi,&nbsp;Pedram Basirjafar,&nbsp;Abdollah Jafarzadeh","doi":"10.1002/cbf.70185","DOIUrl":"10.1002/cbf.70185","url":null,"abstract":"<div>\u0000 \u0000 <p>Apelin, an adipose-derived peptide, is overexpressed in the microenvironment of various tumors, modulating anti-tumor immune responses. In the immune system, cytotoxic T cells perform a fundamental role in cancerous cell elimination. Therefore, inhibiting apelin/APJ can prevent apelin-induced immunosuppression. In this study, we investigated the impact of an apelin receptor antagonist, ML221, on modulating type 1 cytotoxic T (TC1) and TC2 lymphocyte-associated parameters in mice with breast cancer (BC). BC was generated in BALB/c mice by subcutaneous inoculation of 4T1 malignant cells. Phosphate-buffered saline (PBS) or ML221 was administered to the BC-bearing animals for 21 days, starting at 15 days following tumor cell injection. After animal euthanasia on day 37, serum IL-12/IL-4 concentrations and the frequency of splenic TC1/TC2 cells were measured by ELISA and flow cytometry techniques, respectively. BC metastasis to the liver was examined by hematoxylin and eosin staining. Treatment of BC animals with ML221 was more efficient in decreasing tumor growth (<i>p</i> &lt; 0.002), avoiding liver metastases (<i>p</i> &lt; 0.0001), and enhancing the rate of survival (<i>p</i> = 0.001) in comparison to the non-treated group. When compared to the non-treated group, treatment with ML221 substantially raised the frequency of TC1 cells and the TC1/TC2 ratio in the spleen (<i>p</i> &lt; 0.01). Serum IL-12 concentrations and the IL-12/IL-4 ratio were likewise higher in BC mice treated with ML221 (<i>p</i> &lt; 0.05). TC1-associated anti-tumor responses can be improved by apelin/APJ axis suppression, which can contribute to decreasing tumor growth and progression.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147269645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Irisin, Sclerostin, and Inflammatory Axis: Implication in Bone-Muscle Wasting Diseases","authors":"Mohamad Maged,&nbsp;Sameh Heikal,&nbsp;Salma Ibrahim,&nbsp;Sameh E. Hassanein","doi":"10.1002/cbf.70187","DOIUrl":"10.1002/cbf.70187","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Bone-muscle diseases, such as osteoporosis, rheumatoid arthritis, sarcopenia and cachexia, represent a growing global health concern, particularly among aging populations and older adults. These multifactorial disorders are characterized by progressive decline in bone density and muscle mass, increasing the chances of immobility and eventually disability. Such manifestations are driven by a complex molecular crosstalk between bones and muscles. This review highlights the key role of the irisin-sclerostin-inflammation triad in the pathophysiology of musculoskeletal degeneration. Irisin is a myokine induced by exercise. It is associated with osteogenesis and muscle regeneration. Sclerostin is an osteocyte-derived Wnt antagonist, inhibits bone formation and is linked to impaired muscle regeneration. Inflammatory mediators such as TNF-α and IL-6 drive muscle catabolism and bone resorption through the NF-κB and STAT3 signaling pathways. Dysregulation of this triad accelerates musculoskeletal degeneration, particularly in chronic diseases and aging. We described the correlation between these diseases and mediators with age and gender. Additionally, we discussed current and emerging therapeutic strategies targeting these mediators, including anti-sclerostin antibodies for high-risk osteoporosis, cytokine/JAK-pathway inhibitors for inflammatory disease, and structured resistance/weight-bearing exercise as a cornerstone intervention. We highlighted assay standardization needs, proposed human-focused models, and outlined priorities for precision, combination strategies targeting the triad in bone<b>-</b>muscle wasting disorders.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147269627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic Effects of Caffeine and Paclitaxel in Breast Cancer Cells: Mechanistic Insights Into NF-κB and Nrf2 Signaling","authors":"Hasan Gencoglu,&nbsp;Saime Delioglu,&nbsp;Mehmet Akif Nergiz,&nbsp;Rumeysa Metin,&nbsp;Fusun Erten,&nbsp;Muhammed Tokmak,&nbsp;Cemal Orhan,&nbsp;Kazim Sahin","doi":"10.1002/cbf.70183","DOIUrl":"10.1002/cbf.70183","url":null,"abstract":"<div>\u0000 \u0000 <p>Breast cancer remains one of the most prevalent malignancies among women. Recent studies have explored the potential of phytochemicals such as caffeine as chemosensitizing agents in enhancing the efficacy of standard chemotherapeutics like paclitaxel. This study aimed to investigate the cytotoxic, apoptotic, inflammatory, and oxidative stress-related effects of caffeine alone and in combination with paclitaxel in MCF-7 cells. Cells were treated with various concentrations of caffeine (1–100 mM), paclitaxel (0–350 µg/mL), and their combinations for 24, 48, and 72 h. Cell viability was assessed using the MTS assay, and IC₅₀ values were calculated. The expression levels of Bax, Bcl-2, NF-κB, and Nrf2 proteins were analyzed by Western blotting. Both caffeine and paclitaxel induced time- and dose-dependent reductions in MCF-7 cell viability. The combination treatment showed synergistic cytotoxicity, with significantly lower IC₅₀ values compared to single-agent treatments. Western blot analysis showed that both treatments boosted pro-apoptotic Bax and decreased anti-apoptotic Bcl-2, with slightly less effect in the combination group. NF-κB levels increased considerably in caffeine and paclitaxel groups, but were lower in the combination group compared to paclitaxel alone, suggesting a possible reduction in inflammatory signaling. Nrf2 expression increased significantly with caffeine, suggesting oxidative stress responses. In MCF-7 cells, caffeine enhanced paclitaxel's pro-apoptotic and cytotoxic actions and modified inflammation and oxidative stress pathways in a complicated, dose-dependent manner. Cytotoxicity was synergistic; however, apoptotic and stress indicators may be antagonistic. In clinical circumstances, caffeine may be an adjuvant in breast cancer treatment, however mechanistic and in vivo investigations are needed.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146218731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms and Targeted Therapeutic Strategies for Inflammation and Renal Fibrosis in Hyperuricemic Nephropathy","authors":"Lei Xuan,&nbsp;Weiyu Yang,&nbsp;Xiran Luo,&nbsp;Shuya Xiong,&nbsp;Siyi Yang,&nbsp;Yi Si,&nbsp;Wang Rong,&nbsp;Haiyan Jiang,&nbsp;Xiaoxia Wu","doi":"10.1002/cbf.70182","DOIUrl":"10.1002/cbf.70182","url":null,"abstract":"<div>\u0000 \u0000 <p>Hyperuricemia (HUA) is a growing global health issue driven by economic development and lifestyle changes. Approximately 75% of uric acid in humans is excreted renally. Excess uric acid deposits in renal tissues, promoting tubulointerstitial fibrosis and leading to hyperuricemic nephropathy (HN), which is characterized by urate crystal deposition, chronic interstitial nephritis, and renal fibrosis. The pathogenesis and progression of HN involves dysregulated activation of multiple signaling pathways, including MAPK, Nrf2/HO-1/NQO1, PI3K/AKT, and ASK1/JNK/c-Jun pathways, which facilitate disease progression through the production of pro-inflammatory cytokines and other mediators. Current treatments primarily consist of urate-lowering drugs such as allopurinol, febuxostat, benzbromarone, and probenecid, but their use is constrained by adverse effects including hepatotoxicity, nephrotoxicity, and Stevens-Johnson syndrome. Therefore, targeting inflammatory and fibrotic mechanisms presents a promising therapeutic approach. This review outlines key molecular pathways in HN, discusses contemporary research challenges, and suggests future directions for improved therapeutic strategies.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146218643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomic Analysis of Metabolic Syndrome and Effects of Wharton's Jelly Mesenchymal Stem Cell Small Extracellular Vesicles Therapy in Rat Models Using Nuclear Magnetic Resonance Spectroscopy","authors":"Magdalene Tan Mei Ling,&nbsp;Illayaraja Krishnan,&nbsp;Kayatri Govindaraju,&nbsp;Yogeswaran Lokanathan,&nbsp;Teh Chin Hoe,&nbsp;Mohd Rafizul Mohd Yusof,&nbsp;Baskar Subramani,&nbsp;Baharudin Ibrahim","doi":"10.1002/cbf.70180","DOIUrl":"10.1002/cbf.70180","url":null,"abstract":"<div>\u0000 \u0000 <p>Long-term management of metabolic syndrome (MetS) often involves polypharmacy, which may lead to undesirable outcomes. Regenerative approaches such as mesenchymal stem cell–derived small extracellular vesicles (MSC-sEVs) have gained attention due to their paracrine effects, lower immunogenicity, and safer profile compared to whole-cell therapies. Previous studies suggest that MSC-sEVs improve insulin sensitivity, reduce inflammation, and support cardiovascular health, yet their precise mechanisms remain unclear. This study aimed to compare fecal and serum metabolic profiles of healthy, MetS, and MSC-sEVs-treated MetS rats using NMR-based metabolomics and to identify metabolic pathways underlying the therapeutic effects of Wharton's jelly MSC-sEVs (WJMSC-sEVs). 18 Sprague Dawley rats were divided into three groups: healthy controls, MetS + saline, and MetS + WJMSC-sEVs. After 16 weeks of MetS induction, rats received intravenous saline or WJMSC-sEVs every 3 weeks for 12 weeks. Multivariate analysis revealed clear separations between groups. MetS was associated with reduced serum isoleucine, acetate, and propionic acid, and elevated lactate, threonine, and glucose; fecal samples showed increased valine, alanine, leucine, glutamate, and fructose but reduced threonine and SCFAs. Pathway analysis highlighted disturbances in starch and sucrose metabolism, pyruvate metabolism, and alanine, aspartate and glutamate metabolism. WJMSC-sEVs partially restored these imbalances, suggesting their therapeutic potential by targeting key metabolic pathways in MetS.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repositioning Propranolol for Neuroimmune Modulation: A Molecular Perspective on Glial Inflammation and Autophagy via Integrated In Vitro and Computational Approaches","authors":"Dilara Nemutlu Samur","doi":"10.1002/cbf.70181","DOIUrl":"10.1002/cbf.70181","url":null,"abstract":"<div>\u0000 \u0000 <p>Propranolol, a non-selective β-blocker, exerts anti-inflammatory and neuroprotective effects beyond cardiovascular use. However, its role in autophagy remains unclear, despite the relevance of autophagy to neuroinflammatory conditions such as Parkinson's disease. This study integrated in vitro and in silico approaches to explore propranolol's potential modulation of autophagy-related signaling in enteric glial cells (EGCs) under inflammatory stress. EGCs, the representatives of brain astrocytes, were treated with rotenone (10 μM) to induce inflammation, ±propranolol co-treatment (10 and 50 μM). Cell viability was assessed by MTT assay, and expression of glial activation markers (GFAP, S100B) and the autophagy-related gene BECN1 was quantified by RT-qPCR. <i>In silico</i> analyses included SwissTargetPrediction, STRING-based enrichment, and molecular docking against canonical autophagy regulators (BECN1-MTOR-ATG5-ATG7-LC3B). Rotenone significantly increased GFAP and S100B expression, confirming robust glial activation, whereas propranolol markedly attenuated these increases, indicating a clear anti-inflammatory effect. In contrast, propranolol reduced BECN1 expression both alone and in combination with rotenone, suggesting suppression of autophagy initiation rather than restoration of autophagic signaling. Network analyses revealed no direct overlap between propranolol targets and autophagy-related proteins, although several propranolol targets are upstream regulators of autophagy. Docking analyses demonstrated relatively favorable LC3B interaction, although this binding remained weaker than the reference. However, LC3 mRNA expression was undetectable, and docking scores for the other autophagy proteins were modest. These findings suggest propranolol modulates glial activation mainly via autophagy-independent mechanisms, with only limited potential for direct autophagy modulation. In this context, propranolol appears to exert context-dependent neuromodulatory effects on EGCs, warranting further investigation of its potential relevance in modulating neuroinflammatory pathways.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146164306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}