Cell Biochemistry and Function最新文献

{"title":"Biomimetic Shell–Core Nanoparticles Loaded With Apatinib for Dual Starvation and Chemodynamic Combination Therapy of Lung Cancer","authors":"Chao Luo,&nbsp;Guixue Yang,&nbsp;Peng Zhang,&nbsp;Li Jiang,&nbsp;Quanxing Liu","doi":"10.1002/cbf.70242","DOIUrl":"10.1002/cbf.70242","url":null,"abstract":"<div>\u0000 \u0000 <p>Tumor cells rely heavily on vascular nutrient supply and glucose metabolism to sustain proliferation, while maintaining redox homeostasis through reprogrammed antioxidant systems, making it difficult for single starvation therapy or chemodynamic therapy (CDT) alone to achieve durable and effective antitumor efficacy. To address these limitations, we developed a cancer cell membrane (CMC)-coated core–shell biomimetic nanoplatform, termed ACuA@CMC, for synergistically enhanced dual-starvation therapy and CDT. The nanoplatform consisted of a gold nanoparticle (Au NPs) core and a Cu₂O shell. The Au NPs exhibited glucose oxidase-like (GOx-like) activity, enabling continuous glucose depletion and in situ H₂O₂ generation within tumor cells, while the Cu₂O shell further catalyzed H₂O₂ into highly reactive ·OH under the tumor microenvironment, thereby amplifying oxidative stress. Meanwhile, the loaded apatinib (Apa) inhibited tumor angiogenesis and nutrient supply, which synergized with Au NPs-mediated glucose consumption to establish a dual-starvation therapeutic strategy. In addition, CMC coating endowed ACuA@CMC with favorable homologous targeting ability and enhanced cellular uptake efficiency. Experimental results demonstrated that ACuA@CMC possessed favorable physicochemical properties, stability, and hemocompatibility. Moreover, ACuA@CMC significantly enhanced the uptake of nanodrugs by A549 cells, effectively inhibited cell viability, induced apoptosis, elevated intracellular ROS levels, and triggered oxidative stress. Furthermore, the nanoplatform markedly suppressed tumor cell migration and downregulated VEGF expression, exhibiting synergistic anti-migration and anti-angiogenic effects. In summary, this study proposes a synergistic therapeutic strategy for lung cancer based on dual-starvation therapy and cascade CDT-mediated ROS amplification. This work provides a new approach for the development of multifunctional synergistic antitumor nanotherapeutic systems with potential clinical translational value.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148210338","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":"Nerve Growth Factor: A Multifaceted Regulator of Pain, Inflammation, and Tissue Remodeling in Bone and Joint Disorders","authors":"Zuping Wu,&nbsp;Ruifeng Song,&nbsp;Fu Zheng,&nbsp;Xinyi Fang,&nbsp;Yuxuan Wang,&nbsp;Jiajun Liu,&nbsp;Chuan Shen,&nbsp;Qian Chen,&nbsp;Xiaoyan Chen","doi":"10.1002/cbf.70237","DOIUrl":"10.1002/cbf.70237","url":null,"abstract":"<div>\u0000 \u0000 <p>As an essential member of the neurotrophic factor family, nerve growth factor (NGF) plays multifaceted regulatory roles in the pathological processes of bone and joint diseases through its dual signaling mechanisms involving high-affinity receptor TrkA and low-affinity receptor p75NTR. This review systematically examines the profound impact of NGF on bone and joint diseases in multiple aspects, such as bone remodeling, pain perception, and angiogenesis. First, NGF promotes mechanical stress-induced bone formation through the Wnt/β-catenin signaling pathway and regulates osteogenic differentiation through the BMP-2/Smads pathway. Second, by activating the transient receptor potential vanilloid 1 (TRPV1) channel, NGF promotes the release of pain mediators like calcitonin gene-related peptide (CGRP) and substance P (SP). This leads to both peripheral and central sensitization, thereby establishing NGF as a key mediator of chronic pain in osteoarthritis (OA) and intervertebral disc degeneration (IVDD). Third, NGF engages in complex interactions with key inflammatory factors such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Consequently, the pleiotropic nature of NGF renders therapeutic strategies targeting it a double-edged sword. This review summarizes the complex regulatory role of NGF in bone and joint diseases and proposes some potential research directions based on the current research status.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148197295","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":"Differential Cytotoxicity of Hydroxycinnamic Acids in Cancer Cells: Structure–Activity Insights From a Broad Panel of Cell Lines","authors":"Kadriye Aslıhan Onat Taşdelen,&nbsp;Merve Sezer Kürkçü,&nbsp;Hatice Öztürkel Kabakaş,&nbsp;Anara Babayeva,&nbsp;Bekir Çöl","doi":"10.1002/cbf.70241","DOIUrl":"10.1002/cbf.70241","url":null,"abstract":"<div>\u0000 \u0000 <p>Phenolic acids, abundant in plant-based foods, are increasingly investigated for their anticancer potential. This study systematically evaluated the cytotoxic effects of three hydroxycinnamic acids—trans-cinnamic acid (tCA), p-coumaric acid (pCA), and ferulic acid (FA)—across 10 cancer cell lines (A-673, HeLa, PC-3, SW48, HT-29, Caco-2, HUH-7, MG-63, 2A3, CARM-L12-TG3) and one non-cancerous cell line (Phoenix) after 48 and 72 h of treatment. IC₅₀ values were determined via MTT assay. At 48 h, tCA showed the most significant reduction in metabolic activity in Caco-2 and HUH-7 cells, while HT-29 was the most resistant. pCA showed selective potency in A-673 and PC-3 cells, whereas FA demonstrated broad cytotoxic activity, with pronounced effects in SW48 and HeLa cells. Cytotoxicity increased in a time-dependent manner at 72 h. The non-cancerous Phoenix cells were generally less sensitive, supporting the selective inhibitory effect of these compounds toward malignant cells. Statistical analyses revealed highly significant effects of treatment and time factors, with significant treatment and time interactions in A-673, HeLa, and PC-3 cells. These findings indicate that pCA is the most selective compound, FA exerts the broadest cytotoxicity, and tCA shows a balanced but time-dependent effect. Collectively, this study highlights hydroxycinnamic acids as promising scaffolds for developing selective anticancer agents.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148197366","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":"Double-Stranded DNA Sensing cGAS-STING Immune Signaling in a Rat Co-Culture Model of the Blood–Brain Barrier","authors":"András Harazin,&nbsp;Line S. Reinert,&nbsp;Parvez Alam,&nbsp;Lea Hoy,&nbsp;Annemette Boe Marnow,&nbsp;Janni Nielsen,&nbsp;Anna Lorentzen,&nbsp;Daniel E. Otzen,&nbsp;Søren R. Paludan,&nbsp;Morten S. Nielsen","doi":"10.1002/cbf.70240","DOIUrl":"10.1002/cbf.70240","url":null,"abstract":"<p>Double-stranded DNA coming from, for example, viruses, bacteria, or apoptotic cells is recognized by the cGAS-STING signaling pathway comprising the cyclic GMP-AMP synthase (cGAS) and the stimulator of interferon genes (STING) receptors. The pathway induces type I interferon response and activates transcription of interferon-stimulated genes and proinflammatory cytokines. Though the brain is an immune-privileged site, the blood–brain barrier (BBB) elicits inflammatory immune response in neurodegenerative diseases. Parkinson's disease is characterized by α-synuclein oligomer (αSO) aggregates, neurodegeneration, and mitophagy, which potential can activate the cGAS-STING pathway. Here, we studied the cGAS-STING pathway in a co-culture model of the rat BBB treated with and without α-synuclein monomers (αSM) or oligomers (αSO). Activation of the cGAS-STING pathway did not change barrier integrity and junctional protein staining, but it induced the transcription of the interferon-stimulated gene Viperin and the proinflammatory cytokine tumor necrosis factor-α in brain endothelial cells. Furthermore, STING activation increased the protein level of Viperin in astrocytes. The treatment with αSO, but not αSM, decreased barrier tightness and induced the transcription of Viperin and tumor necrosis factor-α in brain endothelial cells. In astrocytes, αSO treatment increased not only Viperin and tumor necrosis factor-α mRNA levels, but also interleukin-1β and interleukin-6. In conclusion, cGAS-STING pathway and downstream immune signaling pathways can be activated in the cells of a co-culture model of the BBB without influencing barrier integrity. However, αSO disrupts the BBB integrity and activates the cGAS-STING immune pathway in brain endothelial cells and astrocytes supporting the idea of using cGAS-STING as a therapeutic target in neuroinflammation.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbf.70240","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155471","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":"Preliminary Evidence of GLUT4 Upregulation and Biocompatibility of Syzygium caryophyllatum-Derived Silver Nanoparticles in 3T3-L1 Preadipocytes","authors":"Santosh Mallikarjun Bhavi,&nbsp;Ramesh Babu Yarajarla","doi":"10.1002/cbf.70236","DOIUrl":"10.1002/cbf.70236","url":null,"abstract":"<div>\u0000 \u0000 <p>AMPK signaling and GLUT4 trafficking are key regulators of cellular glucose handling; however, the effects of biogenic silver nanoparticles (AgNPs) in preadipocyte models remain underexplored. This study characterizes <i>Syzygium caryophyllatum</i>-mediated SC-AgNPs (21.78 nm TEM, <i>λ</i>_max 449 nm) in 3T3-L1 preadipocytes. The identical batch, verified stable by UV–vis and visual inspection, was tested across viability (MTT), ROS (DCFDA), mitochondrial function (TMRE), apoptosis (Annexin V/PI), and AMPK/GLUT4 regulation (endpoint RT-PCR, Western blot) using vehicle controls. SC-AgNPs showed high biocompatibility (IC₅₀ 605.8 μg/mL, &gt; 95% viability at 5–50 μg/mL) with modest changes in cellular responses, including controlled ROS elevation (1.3-fold) and mitochondrial hyperpolarization (2.21-fold), while apoptosis was observed at IC₅₀ (91.7%). At sub-toxic working concentrations, GLUT4 mRNA/protein increased 1.55-/1.6-fold (GAPDH/β-actin normalized), while total AMPK expression decreased (0.2- to 0.7-fold), indicating that the underlying regulatory mechanism remains unclear and requires further investigation. These findings provide preliminary evidence of GLUT4 modulation in 3T3-L1 preadipocytes under non-cytotoxic conditions. However, due to the use of undifferentiated cells and the absence of functional assays, these results should be interpreted cautiously and require validation in differentiated and insulin-resistant adipocyte models.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148027415","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":"Apigenin Enhances the Differentiation of Adipose Tissue-Derived Mesenchymal Stem Cells Into Insulin-Producing Cells by Inducing Autophagy","authors":"Mozafar Khazaei,&nbsp;Zeinab Shakibaee Fard,&nbsp;Maryam Bozorgi,&nbsp;Mohammad Rasool Khazaei,&nbsp;Azam Bozorgi","doi":"10.1002/cbf.70233","DOIUrl":"10.1002/cbf.70233","url":null,"abstract":"<div>\u0000 \u0000 <p>The present study aimed to evaluate the effect of apigenin (Api) on the differentiation of adipose tissue-derived mesenchymal stem cells (ASCs) into insulin-producing cells (IPCs) via inducing autophagy. ASCs were isolated from fresh adipose tissues using mechanical and enzymatic digestion and characterized using flow cytometry. ASCs were treated with Api (0, 5, 10, 25, and 50 µM) for 48 and 72 h, to determine the Api optimum dose using the MTT test. ASCs were exposed to optimal Api doses (5 and 10 µM) and differentiated into IPCs by cultivating them in a differentiation medium in a two-step manner. The expression of IPC and autophagy genes and proteins was evaluated using real-time PCR and Western blot, and glucose-stimulated insulin and C-peptide secretion were assessed using colorimetric methods. Autophagy and β cell-specific protein interactions were analyzed using the STRING database. 94% of ASCs expressed CD73, CD90, and CD105, while 99% didn't express CD34 and CD45. Api treatment increased the expression of PDX1, GLUT2, Insulin, LC3A, ATG5, and ATG7 genes, as well as LC3-1 and LC3-II proteins in a dose-dependent manner. Glucose-stimulated insulin and C-peptide secretion were significantly higher in Api-treated groups. Bioinformatic analysis revealed that MAPK and FOXO3 were central proteins that interacted with and connected β cell-specific and autophagy functional clusters. Api increased the differentiation of ASCs into IPCs by inducing autophagy and can be considered a novel strategy for enhancing differentiation efficiency.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970370","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":"Interpretation of Potential Interactions and Adverse Effects by Apigenin and Chrysin Based on Their Regulation of Metabolizers and Transporters in Mouse Embryonic Fibroblasts","authors":"Prasanth Puthanveetil","doi":"10.1002/cbf.70232","DOIUrl":"10.1002/cbf.70232","url":null,"abstract":"<div>\u0000 \u0000 <p>Apigenin and chrysin are chemically close and related flavonoids. Our previous works have demonstrated both apigenin and chrysin's ability to reduce cholesterol and uric acid biosynthesis along with upregulation of ketone bodies and endogenous anti-inflammatory lipids. Current work based on transcriptomics approach has shed light into their ability to influence endogenous metabolites or xenobiotic metabolism by regulating CYP isoforms. This work is based on analyzing raw data for transcriptomics, which we previously performed on mouse embryonic fibroblasts (MEFs). Following transcriptomics, we have added our raw data to NIH – Gene Expression Omnibus (GEO) with Accession Number – GSE155852. We have selected top 5 altered targets which are CYP450 family members and provided our perspective on how apigenin or chrysin administration could influence our metabolic status or drug metabolizing ability. In addition, we have also analyzed the impact of apigenin and chrysin treatment on glutathione S-transferase and ATP-binding cassette family members. This work will really shed light upon metabolizing and drug interaction capabilities of these flavonoids through the regulation of major cellular drug metabolizers and transporters.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970307","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 Anticancer Effects of Akkermansia muciniphila Combined With 5-Fluorouracil Through BAX/BCL2 Dependent Apoptosis in Colorectal Cancer Cells","authors":"Soumaya Menadi,&nbsp;Ercan Cacan","doi":"10.1002/cbf.70234","DOIUrl":"10.1002/cbf.70234","url":null,"abstract":"<div>\u0000 \u0000 <p>Colorectal cancer (CRC) continues to be one of the deadliest cancers worldwide, mainly due to late diagnosis, chemoresistance, and the complex interactions within the tumor microenvironment. Recent studies suggest that the gut bacterium <i>Akkermansia muciniphila</i> plays a key role in maintaining intestinal health and may influence the effectiveness of cancer therapies. Therefore, the main aim of this study was to explore whether a lyophilized form of <i>A. muciniphila</i> could support CRC treatment. First, we analyzed <i>A. muciniphila</i> abundance in healthy, adenoma, and CRC tissues using public datasets. Next, CRC cell lines (HT29, HCT116, and SW620) and normal stromal cells (Hs738 St/Int) were treated with increasing doses of the bacterial extract, alone and with 5-fluorouracil (5-FU). Then, cell viability measured by MTT assay, apoptosis by BAX/BCL2 expression via RT-qPCR, and physicochemical properties by zeta potential analysis. The results showed a marked reduction of <i>A. muciniphila</i> abundance in CRC samples, with an early decline from healthy to adenoma tissues and a slight recovery in advanced tumors. In vitro, the extract demonstrated dose-dependent cytotoxicity toward cancer cells, with HT29 showing strong sensitivity at low doses, HCT116 responding at higher concentrations, and SW620 exhibiting greater resistance. Importantly, the extract was well tolerated by normal cells, unlike 5-FU. Combining the extract with 5-FU resulted in a synergistic effect, indicating the possibility of reducing 5-FU dosage to limit its toxicity. The extract significantly upregulated BAX, downregulated BCL2, and displayed strong negative zeta potential, supporting enhanced apoptotic activation and selective interaction with cancer cell membranes. These findings suggest that <i>A. muciniphila</i> and its derived products may serve as promising adjuncts in personalized microbiome-based CRC therapy.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970326","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":"Single Intra-Articular Anakinra (IL-1Ra) Versus Betamethasone in Rabbit Post-Traumatic Knee Osteoarthritis: IL-8 Suppression and Chondrocyte Viability","authors":"Hüseyin Emre Tepedelenlioğlu,&nbsp;Duygu Dayanir,&nbsp;Zübeyir Elmazoğlu,&nbsp;Candan Özoğul,&nbsp;Akif Muhtar Öztürk,&nbsp;Emin Ertuğrul Şener,&nbsp;Çimen Karasu","doi":"10.1002/cbf.70230","DOIUrl":"10.1002/cbf.70230","url":null,"abstract":"<p>Post-traumatic osteoarthritis (OA) is driven by a sustained inflammatory response and progressive osteochondral damage. We compared the effects of a single intra-articular injection of anakinra (Interleukin-1 receptor antagonist; IL-1Ra) with those of betamethasone on structural cartilage outcomes and Interleukin-8 (IL-8) immunopositivity in a rabbit model of post-traumatic knee OA, and assessed the cytotoxicity of anakinra in primary human OA chondrocytes. Fifteen male New Zealand White rabbits underwent bilateral anterior cruciate ligament transection and partial medial meniscectomy and were randomized to receive saline (OA, control), betamethasone (0.5 mg/kg), or anakinra (0.6 mg/kg) at 2 weeks post-surgery (<i>n</i> = 5 rabbits/group; 10 knees/group, clustered within rabbit). At 14 weeks, cartilage damage was graded using the Osteoarthritis Research Society International (OARSI) cartilage OA pathology assessment system, and IL-8 immunopositivity in cartilage was quantified by immunohistochemistry. In vitro, chondrocytes from seven donors (Passages 0–1) were treated with anakinra (1 µM to 1 mM) for 24 h, and cell viability was evaluated by MTT and neutral red uptake (NRU) assays. Both anakinra and betamethasone shifted the OARSI grade distribution toward lower grades compared with OA (<i>p</i> &lt; 0.001), with no difference between the treatments (<i>p</i> = 0.639). IL-8 immunopositivity was lower with both treatments and was lowest in the anakinra group (OA: 93.09 ± 6.1%; betamethasone: 22.93 ± 3.4%; anakinra: 9.58 ± 3.9%) (<i>p</i> &lt; 0.01 OA vs. betamethasone; <i>p</i> &lt; 0.001 OA vs. anakinra). Anakinra did not reduce chondrocyte viability at concentrations up to 500 µM (<i>p</i> &gt; 0.05), whereas 1 mM reduced viability by approximately 10% (<i>p</i> &lt; 0.05). These findings suggest that a single-dose intra-articular anakinra injection modulates the histomorphological characteristics of damaged cartilage by preserving chondrocyte viability and inhibiting IL-8 expression in post-traumatic knee OA.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13173311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147926642","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":"Chronic Mild Unpredictable Stress Selectively Downregulates Exon I Bdnf mRNA in the Rat Frontal Cortex Independently of Anhedonia","authors":"Mikhail Stepanichev,&nbsp;Danil Peregud,&nbsp;Anna Manolova,&nbsp;Pavel Gusev,&nbsp;Sofia Freiman,&nbsp;Natalia Lazareva,&nbsp;Natalia Gulyaeva","doi":"10.1002/cbf.70225","DOIUrl":"10.1002/cbf.70225","url":null,"abstract":"<div>\u0000 \u0000 <p>Chronic stress is often a precursor to depression. Multiple brain mechanisms underlying the development of depression involve alterations in neurotrophin signaling. In the present study, male Wistar rats were exposed to chronic mild unpredictable stress (CMS), a well-known rodent model of depression, in order to investigate changes in BDNF content, BDNF mRNA expression, and BDNF receptor expression in different brain regions. After 8 weeks of CMS, anhedonia, a symptom of a depressive state, developed in 35% of stressed rats, while 65% remained resilient. The CMS treatment did not significantly affect the BDNF content as measured by ELISA in the frontal cortex, other neocortical regions, the hippocampus, and the medulla oblongata. The levels of exon I <i>Bdnf</i> mRNA decreased in the frontal cortex of both anhedonic and resilient rats. No changes were observed in exons IV, VI and IX in any of the studied brain structures, except for the hippocampus of anhedonic rats, where there was a tendency toward decreased exon IX <i>Bdnf</i> mRNA. The levels of <i>Ntrk2</i> and <i>Ngfr</i> mRNAs did not significantly change in the brain after CMS. Therefore, the alterations in the expression of exon I <i>Bdnf</i> mRNA observed in this study were caused by chronic stress but were not associated with depression-like anhedonia.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147873538","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}