{"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, Duygu Dayanir, Zübeyir Elmazoğlu, Candan Özoğul, Akif Muhtar Öztürk, Emin Ertuğrul Şener, 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> < 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> < 0.01 OA vs. betamethasone; <i>p</i> < 0.001 OA vs. anakinra). Anakinra did not reduce chondrocyte viability at concentrations up to 500 µM (<i>p</i> > 0.05), whereas 1 mM reduced viability by approximately 10% (<i>p</i> < 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}
Mikhail Stepanichev, Danil Peregud, Anna Manolova, Pavel Gusev, Sofia Freiman, Natalia Lazareva, Natalia Gulyaeva
{"title":"Chronic Mild Unpredictable Stress Selectively Downregulates Exon I Bdnf mRNA in the Rat Frontal Cortex Independently of Anhedonia","authors":"Mikhail Stepanichev, Danil Peregud, Anna Manolova, Pavel Gusev, Sofia Freiman, Natalia Lazareva, 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}
Jalal Taneera, Abdul Khader Mohammed, Hind Mohammed Abed Abu Shaireh, Alaa Al Hajji, Amani Al Hajji, Mutaz Al Gharaibeh, Hany Dewedar, Fatheya S. AlKhaja, Mawieh Hamad
{"title":"Elevated Circulating Follistatin Is Associated With Diabetic Status and Glycemic Dysregulation in Patients With β-Thalassemia Major","authors":"Jalal Taneera, Abdul Khader Mohammed, Hind Mohammed Abed Abu Shaireh, Alaa Al Hajji, Amani Al Hajji, Mutaz Al Gharaibeh, Hany Dewedar, Fatheya S. AlKhaja, Mawieh Hamad","doi":"10.1002/cbf.70226","DOIUrl":"10.1002/cbf.70226","url":null,"abstract":"<div>\u0000 \u0000 <p>Diabetes mellitus (DM) is a frequent and debilitating complication in patients with β-thalassemia major (β-TM), driven by chronic iron overload–induced pancreatic and hepatic dysfunction. Validated biomarkers for early diabetes detection in this population remain limited. Follistatin (FST), a secreted glycoprotein modulating TGF-β/activin signaling and glucose metabolism, has been associated with Type 2 diabetes (T2D), though its relevance to thalassemia-associated diabetes is unexplored. This cross-sectional study examined plasma FST levels and gene expression relative to diabetic status and glycemic control in 134 participants: 80 β-TM/non-diabetic, 34 β-TM/diabetic patients, and 20 healthy controls. Iron modulation effects were explored in HepG2 hepatocytes using ferric ammonium citrate (FAC) or deferoxamine (DFO), and metabolic stress effects were assessed in healthy PBMCs exposed to high glucose or insulin. Plasma FST was significantly elevated in β-TM/diabetic patients versus β-TM/non-diabetic patients or controls (<i>p</i> < 0.001). FST correlated positively with glucose and fructosamine (<i>r</i> = 0.23; <i>p</i> ≤ 0.02), but not with serum ferritin. A stepwise increase in plasma FST was observed across glycemic control subgroups, from 2421 pg/mL in well-controlled to 3831 pg/mL in poorly controlled diabetics (<i>p</i> < 0.0001). FAC upregulated FST mRNA in HepG2 cells, while DFO suppressed it (<i>p</i> < 0.05). Peripheral Blood Mononuclear Cells (PBMCs) FST mRNA was paradoxically lower in β-TM/diabetic patients (<i>p</i> = 0.02), a pattern reproduced in PBMCs under high glucose or insulin, indicating tissue-specific metabolic regulation. Collectively, these findings suggest that elevated plasma FST may reflect a convergence of iron-induced hepatic stress and hyperglycemia-related dysregulation and warrant further cross-sectional investigations as a candidate biomarker in this population.</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":"147873487","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}
J. Logan Jenkins, Pratheepa Kumari Rasiah, Jacob Hardenburger, Wilson Adams, Anita Mahadevan-Jansen, Bryan Millis, E. Duco Jansen
{"title":"Neuroglial Response to High-Amplitude, Short-Duration Pressure Transients in Monoculture","authors":"J. Logan Jenkins, Pratheepa Kumari Rasiah, Jacob Hardenburger, Wilson Adams, Anita Mahadevan-Jansen, Bryan Millis, E. Duco Jansen","doi":"10.1002/cbf.70231","DOIUrl":"10.1002/cbf.70231","url":null,"abstract":"<p>Blast-induced traumatic brain injury (bTBI) was reported in 125,000 U.S. service men and women from 2000 to 2018. With no prophylactic treatments having been granted FDA approval, there is a clear need for further understanding of the impact of blasts on the central nervous system. The biological response of brain cells due to the near-instantaneous overpressure of blast onset remains unresolved. Laser-induced pressures isolate high-amplitude, short-duration pressure transients, similar to the initial peak of blast pressures. In this study, we uncover the effects of high-amplitude, short-duration pressure transients on monocultures of astrocytes, microglia, and neurons through intracellular calcium imaging, cell viability assays, and quantifying intracellular and extracellular immune signaling proteins. The results indicate that while all three cell types follow a similar activation curve for induced intracellular calcium transients, the downstream impact of high-amplitude, short-duration pressures on neurons and glia deviate. Neurons are particularly susceptible to non-reversible damage, while glia activates traditionally neuroprotective pathways rather than neurodegenerative pathways in response to high-amplitude, short-duration pressures. This work has important implications for developing countermeasures for bTBI with either the high-frequency component of a blast wave or the effects of that component being potential targets for prevention.</p>","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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13162088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147873499","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":"The Role of Iron in Adipose Tissue Function, Crosstalk, and Transdifferentiation","authors":"Jiamin Guo, Panpan Yu, Chenkang Li, Guiying Nie, Wenchen Xu, Meiyi Chen, Liang Li, Tianhong Peng, Wei Xie","doi":"10.1002/cbf.70229","DOIUrl":"10.1002/cbf.70229","url":null,"abstract":"<div>\u0000 \u0000 <p>Brown adipose tissue (BAT) plays a crucial role in human physiology and holds significant therapeutic potential for metabolic disorders, including obesity and type 2 diabetes. White adipocytes possess the capacity to transdifferentiate into brown-like adipocytes under specific stimuli, a process termed white adipose tissue (WAT) browning. A key therapeutic strategy for metabolic diseases is to induce WAT browning, which enhances energy expenditure, improves glucose and lipid homeostasis, and reduces insulin resistance. Iron, the most abundant trace element in the body, plays a critical role in regulating adipocyte development, function, and transdifferentiation. This review critically examines the mechanisms through which iron imbalance influences adipocyte transdifferentiation and evaluates its promise as a therapeutic target for metabolic disorders.</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":"147873527","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":"Cholesterol and Its Journey Over the Centuries (1769−2025): The Highlights and Challenges","authors":"Koshankan Chandra, Nimai Chand Chandra","doi":"10.1002/cbf.70227","DOIUrl":"10.1002/cbf.70227","url":null,"abstract":"<div>\u0000 \u0000 <p>Cholesterol is a beneficial lipid molecule considering its multifunctional roles to support physiological homeostasis and the progression of biological system at various levels, namely, membrane integrity, cushioning quality, nutrient skill, as well as its ventures as metabolic forerunner, for example, precursor of bile acids and bile salts, vitamin D, steroid hormones, and so on. On the other hand, excess load of cholesterol in systemic compartments, for example, blood vessels, and intracellular or intraorganellar rooms may end up with serious detrimental consequences, namely, heart attack, diabetes, carcinogenesis, and organ or organelle storage disorders. With this view, cholesterol is a biotic handler of both bright and dark edges. Since its discovery, cholesterol has been sequeled with differential challenges of the life process, either advantageous or disadvantageous. Advantageous features are associated with essential physiological processes, and disadvantageous attributes are the marks of metabolic malfunctioning from the incidents cropped up either by its overuse or from multifactorial circumstantial interferences, for example, carcinogens, obesity, inflammation, therapeutic side effects, and so on.</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":"147926644","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}
Laura Prieto-López, Christian van Oterendorp, Elena Vecino, Xandra Pereiro
{"title":"Shear Stress as a Driver of Retinal Müller Glia Survival and Fibrotic Reprogramming","authors":"Laura Prieto-López, Christian van Oterendorp, Elena Vecino, Xandra Pereiro","doi":"10.1002/cbf.70224","DOIUrl":"10.1002/cbf.70224","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>The retina is highly influenced by mechanical cues such as intraocular fluid movement and blood flow, generating shear stress implicated in both retinal development and pathology. Müller glia, as retinal mechanosensors, are uniquely positioned to respond to such forces. This study examined Müller glia responses to flow-induced shear stress. Primary adult rat Müller glia were cultured in a single-channel microfluidic system and exposed to fluid shear stress (10<sup>−3</sup> dyn/cm<sup>2</sup>) for 24 h. Müller glia survival, morphology, and extracellular matrix (ECM) remodelling were evaluated. Expression of the mechanosensitive ion channel TRPV4, phosphorylated focal adhesion kinase (pFAK), and the pro-fibrotic cytokine TGF-β1 was analysed. TRPV4 and TGF-β1 were pharmacologically inhibited to assess their functional roles. The results showed that shear stress enhanced Müller glia survival and reduced cell area. TRPV4 expression increased under flow, and its inhibition decreased survival and reversed morphological changes. Shear stress also elevated pFAK levels in a TRPV4-dependent manner. Similarly, TGF-β1 expression increased with flow, and its inhibition decreased survival and altered cell morphology under both static and flow conditions. ECM remodelling involved increased intracellular collagen I and IV levels and enhanced fibronectin deposition, both regulated by TGF-β1. In conclusion, shear stress induces Müller glia survival, cytoskeletal remodelling, and selective ECM regulation via TRPV4 and TGF-β1. TRPV4 acts upstream through pFAK signalling, while TGF-β1 controls ECM remodelling. Together, these pathways initiate early remodelling and contraction, potentially driving retinal fibrosis post-injury. Targeting TRPV4 and TGF-β1 may offer therapeutic strategies to limit glial scarring and preserve retinal structure.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13161832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147873464","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":"Isolation and Identification of Bacillus velezensis G52 and Its Growth-Promoting Mechanism on Navel Orange Seedlings","authors":"Wenyuan Zhao, Tao Peng, Haojie Cao, Huimin Huang, Ruiqi Liu, Shuijing Yu","doi":"10.1002/cbf.70222","DOIUrl":"10.1002/cbf.70222","url":null,"abstract":"<div>\u0000 \u0000 <p>This study isolated and screened a multifunctional plant-growth-promoting bacterium, Bacillus sp. G52, from the rhizosphere soil of Gannan navel oranges. Through pot experiments and genomic analysis, the growth-promoting effects and molecular mechanisms of strain G52 on navel orange seedlings were systematically evaluated. The results showed that strain G52 could secrete indole-3-acetic acid (IAA, yield: 18.68 ± 0.81 mg/L), siderophores (yield: 47.10 ± 1.03%), and phosphate-solubilizing substances (91.85 ± 4.94 mg/L) while also exhibiting ACC deaminase activity and ammonia production. Pot experiments demonstrated that inoculation with G52 significantly increased seedling height (12.51%), stem diameter (10.97%), biomass (27.87% in shoots, 41.13% in roots), and chlorophyll content (37.40% increase in total chlorophyll). Additionally, G52-treated seedlings showed enhanced antioxidant enzyme activities (SOD, POD, CAT), indicating improved stress resistance. Genomic analysis revealed that G52 carries functional genes related to IAA synthesis (e.g., trpA-trpF) and siderophore production (e.g., ent gene cluster), further confirming the molecular basis of its growth-promoting potential. Phylogenetic analysis indicated a 99.7% similarity between G52 and <i>Bacillus velezensis</i>. This study provides a theoretical foundation for developing multifunctional Bacillus-based biofertilizers, contributing to sustainable agricultural development.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763521","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}