Cell. Physiol. Biochem. [JOURNAL]
Sun
200 papers
Advances in the Study of Bronchial and Vascular Architecture of Lungs in the Rat's Model: from Morphogenesis to Disease Modelling.
Aliyar AA, Eldar AS, Sadig SA … +3 more , Mubariz GT, Adil MN, Aydın AS
Cell Physiol Biochem · 2025 Dec · PMID 41536246 · Publisher ↗
Bronchial and vascular architecture in the rat lung forms an interdependent scaffold that balances ventilation with perfusion and adapts to metabolic demand. Development proceeds through coordinated branching programs th...
Bronchial and vascular architecture in the rat lung forms an interdependent scaffold that balances ventilation with perfusion and adapts to metabolic demand. Development proceeds through coordinated branching programs that couple epithelial growth with vascular patterning while matrix remodeling and epithelial-mesenchymal crosstalk shape airway caliber and capillary alignment. Quantification has moved from classical design-based stereology to organ-scale µCT, optical clearing, and multiscale computational reconstructions that link structure to function. Across disease models, Chronic Obstructive Pulmonary Disease (COPD) and emphysema show distal airspace enlargement with vascular rarefaction, pulmonary hypertension (PH) features medial thickening and arteriolar muscularization, asthma combines epithelial remodeling with angiogenesis, and fibrosis exhibits collagen deposition with capillary regression. Convergent signaling networks integrate these changes, including VEGF and HIF pathways that govern angiogenesis, Notch and Wnt programs that regulate morphogenesis, and oxidative stress with cytokine and microRNA axes that drive vascular remodeling. Translational alignment is strengthened by single-cell and imaging biomarkers that map rat phenotypes to human pathology, while bioengineered platforms and in silico models provide controllable test beds for hypothesis testing. Predictive frameworks for remodeling across development and disease could be provided by standardized pipelines that combine morphometry, mechanics, and molecular profiles.
Management of Sudden Onset Sensorineural Hearing Loss and the Role of Pentoxyphylline as an Add-on Therapy to Conventional Treatment.
Gajendran A, Cheruvu SC, Pradeep A … +2 more , Athikesavan R, Ramesh XRW
Cell Physiol Biochem · 2025 Mar · PMID 41527825
BACKGROUND/AIMS: Sudden Sensorineural Hearing Loss (SSNHL) is a rapid-onset condition with varied etiologies, creating uncertainty in optimal treatment strategies. This study aimed to assess whether adding pentoxifylline...
BACKGROUND/AIMS: Sudden Sensorineural Hearing Loss (SSNHL) is a rapid-onset condition with varied etiologies, creating uncertainty in optimal treatment strategies. This study aimed to assess whether adding pentoxifylline to standard antiviral and steroid therapy could enhance hearing recovery in SSNHL patients. METHODS: This randomized controlled trial was conducted between January 2021 and June 2023 in a private clinic in Chennai district, Tamil Nadu. Seventy-two patients aged 20-70 years with SSNHL onset within 7 days were randomized to receive either standard therapy (antiviral and steroids) or additional pentoxifylline. Serial pure-tone audiometry was performed to evaluate hearing recovery. RESULTS: The intervention group showed significantly improved hearing recovery, particularly when treatment was initiated within 72 hours of symptom onset. Non-responders underwent MRI of the brain, revealing cerebellopontine angle pathology in selected cases. Statistical analysis confirmed superior outcomes with pentoxifylline add-on therapy (p < 0.05). CONCLUSION: Pentoxifylline may enhance hearing recovery when combined with antiviral and steroid therapy in SSNHL, especially when administered early. Intratympanic dexamethasone and MRI are recommended for non-responders.
Retraction.
Cell Physiol Biochem · 2025 Aug · PMID 41496598 · Publisher ↗
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Erratum.
Cell Physiol Biochem · 2025 Aug · PMID 41496597 · Publisher ↗
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Lnc-ANRIL Protects Against Myocardial Ischemia-Reperfusion Injury by Suppressing Ferroptosis via the miR-7238-3p/GPX4 Axis.
Liu Y, Wu B, Shao Y … +4 more , Hu K, Mo J, Zhang L, Mo G
Cell Physiol Biochem · 2025 Dec · PMID 41480995 · Publisher ↗
BACKGROUND/AIMS: Myocardial infarction remains a leading cause of cardiovascular morbidity and mortality. Although reperfusion therapy restores myocardial blood flow, it can induce myocardial ischemia-reperfusion injury...
BACKGROUND/AIMS: Myocardial infarction remains a leading cause of cardiovascular morbidity and mortality. Although reperfusion therapy restores myocardial blood flow, it can induce myocardial ischemia-reperfusion injury (MI/RI). Ferroptosis, an iron-dependent form of regulated cell death driven by excessive lipid reactive oxygen species, contributes to MI/RI and is characterized by downregulation of GPX4 and upregulation of ACSL4. LncRNA ANRIL is aberrantly expressed in acute myocardial infarction and may provide myocardial protection, but its role in MI/RI-induced ferroptosis is unclear. METHODS: A mouse MI/R model was established by ligating the left anterior descending coronary artery in C57BL/6 mice. HL-1 and H9C2 cardiomyocytes underwent hypoxia-reoxygenation to simulate MI/RI in vitro. Lnc-ANRIL was overexpressed using pEGFP-lnc-ANRIL or silenced using siANRIL. Ferroptosis indicators (ROS, malondialdehyde, Fe2+, GPX4, ACSL4) were assessed. Candidate miRNAs targeting lnc-ANRIL and GPX4 were predicted (miRDB) and validated by dual-luciferase assays. RESULTS: Ferroptosis was activated in MI/R tissues and hypoxia-reoxygenation-treated cardiomyocytes, with decreased GPX4, increased ACSL4, and elevated ROS, malondialdehyde, and Fe2+. Lnc-ANRIL expression was reduced. Overexpression of lnc-ANRIL attenuated ferroptosis markers and increased GPX4, whereas lnc-ANRIL silencing exacerbated ferroptosis. Mechanistically, lnc-ANRIL acted as a sponge for miR-7238-3p, which targets the 3'-UTR of GPX4 to suppress expression. Overexpression of miR-7238-3p enhanced ferroptosis and cardiomyocyte damage. CONCLUSION: MI/RI downregulates lnc-ANRIL, relieving inhibition of miR-7238-3p and suppressing GPX4, thereby triggering ferroptosis in cardiomyocytes. Lnc-ANRIL protects against MI/RI-induced ferroptosis via the miR-7238-3p/GPX4 axis, suggesting a potential therapeutic target.
The Effect of 6-Gingerol on Human AML Cell Lines.
Zhang T, Kong C, Li A … +5 more , Cheng H, Ding W, Ke B, Chen C, Wu M
Cell Physiol Biochem · 2025 Dec · PMID 41480969 · Publisher ↗
BACKGROUND/AIMS: Acute myeloid leukemia (AML) is a devastating hematological malignancy without a definitive cure. 6-Gingerol, a bioactive compound, has shown promise in treating various cancers, yet its impact on AML re...
BACKGROUND/AIMS: Acute myeloid leukemia (AML) is a devastating hematological malignancy without a definitive cure. 6-Gingerol, a bioactive compound, has shown promise in treating various cancers, yet its impact on AML remains elusive. METHODS: Cell growth and clonogenic capacity were assessed using CCK-8 testing and colony formation assays. Flow cytometry was employed to analyze cell cycle progression and apoptosis. The invasive capability of AML cells was evaluated through the Transwell migration assay. Fluorescent probe staining was used to determine intracellular reactive oxygen species (ROS) concentration, while Western blot was utilized to assess the expression levels of key proteins including Bcl-2, caspase3, MAPK, and p-MAPK in AML cells. Potential targets of 6-gingerol in AML were identified through bioinformatics databases (STP, SEA, STICH, OMIM GeneMap, GeneCards). GO and KEGG enrichment analysis was performed using clusterProfiler (v4.16.0). RESULTS: 6-Gingerol inhibited proliferation, colony formation, and invasive capacity of AML cells and induced G1 cell-cycle arrest. 6-Gingerol increased ROS and elevated caspase 3, MAPK, and p-MAPK levels. Sixty-seven overlapping targets between 6-gingerol and AML were identified and enriched in MAPK signaling and ROS-related pathways. NFKB1 emerged as a pivotal hub gene. CONCLUSION: 6-Gingerol may represent a promising Traditional Chinese Medicine-derived agent for AML treatment.
3-Acetyl-11-Keto-Beta-Boswellic Acid Inhibits Adipogenesis by Suppressing Autophagy and Inducing AMPK Phosphorylation in 3T3-L1 Cells.
Khan F, Waqas M, Moghtaderi H … +6 more , Rehman NU, Avula SK, Khan H, Choudhury M, Al-Harrasi A, Rahman SM
Cell Physiol Biochem · 2025 Nov · PMID 41480961 · Publisher ↗
BACKGROUND/AIMS: Adipogenesis involves preadipocyte differentiation and lipid droplet accumulation and is closely linked to obesity. 3-Acetyl-11-keto-beta-boswellic acid (AKBA), a frankincense-derived triterpene, has ant...
BACKGROUND/AIMS: Adipogenesis involves preadipocyte differentiation and lipid droplet accumulation and is closely linked to obesity. 3-Acetyl-11-keto-beta-boswellic acid (AKBA), a frankincense-derived triterpene, has anti-inflammatory and anticancer properties, but its role in adipocyte differentiation remains unclear. METHODS: 3T3-L1 preadipocytes were induced to differentiate with or without varying concentrations of AKBA. Cell viability was assessed by MTT assay, lipid accumulation by Oil Red O staining, and apoptosis by annexin V-FITC assay. Expression of adipogenic transcription factors, lipid-associated proteins, apoptotic markers, autophagy-related proteins, and AMPK phosphorylation was analysed by Western blotting. Molecular docking was used to evaluate AKBA interactions with target proteins. RESULTS: AKBA inhibited adipocyte differentiation by suppressing C/EBPβ, C/EBPα, and PPARγ expression, reduced lipid accumulation, increased apoptosis via an elevated Bax/Bcl2 ratio, suppressed autophagy markers ATG5 and LC3b, and enhanced AMPK phosphorylation. Docking studies suggested AKBA binding to PPARγ and ATG5. CONCLUSION: AKBA suppresses adipogenesis by inhibiting adipogenic transcription factors, autophagy, and activating AMPK, supporting its potential as an anti-obesity therapeutic candidate.
Effect of Isobutylparaben and Phenylmercuric Acetate on Juvenile Female Rats with Special Reference to Development, Neurobehavior, and Histopathology.
Darekar VB, Indur B
Cell Physiol Biochem · 2025 Oct · PMID 41480865 · Publisher ↗
BACKGROUND/AIMS: Isobutylparaben (IBP) and phenylmercuric acetate (PMA) are extensively applied in pharmaceuticals, cosmetics, and industrial chemicals, and are of concern for developmental toxicity. This study was condu...
BACKGROUND/AIMS: Isobutylparaben (IBP) and phenylmercuric acetate (PMA) are extensively applied in pharmaceuticals, cosmetics, and industrial chemicals, and are of concern for developmental toxicity. This study was conducted to compare and assess the subchronic effects of IBP and PMA on growth, neurobehavior, reproduction, and organ integrity in juvenile female rats, and establish no-observed-adverse-effect levels (NOAELs). METHODS: Juvenile female Sprague-Dawley rats (n=10/group) were given IBP (10, 20, 50 mg/kg/day) or PMA (2, 4, 8 mg/kg/day) by gavage for 70 days. Assays encompassed growth assessment, onset of puberty (vaginal opening), estrous cyclicity (vaginal smears), neurobehavioral examination (open-field activity, sensory reflexes, grip strength, motor activity), haematology, serum biochemistry, thyroid hormones (ELISA), organ weights, and histopathology of reproductive, hepatic, and renal tissues. RESULTS: IBP and PMA at high doses significantly inhibited terminal body weight, postponed vaginal opening, disrupted motor function, and affected exploratory behavior. Biochemical indicators revealed hepatic and renal stress and histological findings of hepatocellular hypertrophy and renal tubular degeneration. PMA was somewhat more toxic. NOAELs were 20 mg/kg/day (IBP) and 4 mg/kg/day (PMA). CONCLUSION: Both IBP and PMA caused dose-dependent developmental toxicity, calling for more stringent pediatric exposure evaluations and chemical safety regulations.
Allopurinol Attenuates Senescence and Oxidative Stress in Endothelial Cells Exposed to Serum from Hypertensive Patients with Hyperuricemia - a Pilot Study.
Lewandowska K, Mikuła-Pietrasik J, Książek K … +2 more , Tykarski A, Uruski P
Cell Physiol Biochem · 2025 Oct · PMID 41480862 · Publisher ↗
BACKGROUND/AIMS: Endothelial cell senescence is a key contributor to the development of vascular pathologies, including arterial hypertension. Uric acid has been shown to promote oxidative stress and inflammation, thereb...
BACKGROUND/AIMS: Endothelial cell senescence is a key contributor to the development of vascular pathologies, including arterial hypertension. Uric acid has been shown to promote oxidative stress and inflammation, thereby accelerating endothelial dysfunction and senescence. Although xanthine oxidase inhibition with allopurinol has demonstrated cardiovascular benefits, its effect on endothelial senescence remains insufficiently characterised. This study aimed to investigate the impact of sera from patients with arterial hypertension and elevated uric acid levels on the senescence of human umbilical vein endothelial cells, and to determine whether allopurinol treatment modulates this effect. MATERIALS: Human umbilical vein endothelial cells were cultured and exposed to sera from hypertensive patients with elevated uric acid levels (≥5 mg/dL) before and after six weeks of allopurinol treatment (300 mg/day). A control group consisting of healthy individuals with normal uric acid levels was established. Eighteen participants of both sexes were recruited to the study. Markers of senescence (SA-β-Gal, γ-H2A.X, 53BP1), oxidative stress (mitochondrial and cytosolic reactive oxygen species, mitochondrial mass, membrane potential), cell proliferation and inflammatory cytokine production were analysed. RESULTS: Sera from hypertensive patients before treatment induced endothelial senescence and oxidative stress and altered secretory profiles in endothelial cells compared to controls; however, allopurinol treatment led to a partial reversal of these changes, including reduced mitochondrial reactive oxygen species, mitochondrial mass and γ-H2A.X levels, and increased cell proliferation. Not all markers returned to baseline, and some inflammatory mediators remained elevated or increased after treatment. CONCLUSION: Allopurinol partially reverses uric acid- and hypertension-related endothelial senescence and oxidative damage, but incomplete normalisation suggests multiple overlapping pathways contribute to vascular cell senescence in this context.
Conifer Essential Oils Modulate Oxidative Stress and Erythrocyte Stability in Human Blood in Vitro.
Tkaczenko H, Wróblewski T, Ushakou D … +3 more , Mochalski P, Buyun L, Kurhaluk N
Cell Physiol Biochem · 2025 Dec · PMID 41405564 · Publisher ↗
BACKGROUND/AIMS: Essential oils (EOs) derived from conifers of the Pinaceae family are complex bioactive mixtures known for their antioxidant and antimicrobial properties. However, their impact on human redox homeostasis...
BACKGROUND/AIMS: Essential oils (EOs) derived from conifers of the Pinaceae family are complex bioactive mixtures known for their antioxidant and antimicrobial properties. However, their impact on human redox homeostasis, particularly in blood, remains poorly understood. This study aimed to compare the redox-modulating and membrane-stabilising effects of essential oils from Scots pine (PEO), European spruce (SEO), and European silver fir (FEO) using an in vitro human blood model. METHODS: The chemical composition of each EO was characterised using gas chromatography-mass spectrometry (GC-MS), proton-transfer-reaction mass spectrometry (PTR-MS), and Fourier-transform infrared spectroscopy (FTIR). Human blood samples were incubated with different EO concentrations, and oxidative stress biomarkers, antioxidant enzyme activities, and erythrocyte membrane stability were evaluated. RESULTS: All EOs exhibited terpene-rich profiles dominated by α-pinene, β-pinene, borneol, and bornyl acetate, with distinct species-specific differences. The oils displayed concentration-dependent biphasic redox effects. At moderate concentrations, PEO and SEO enhanced total antioxidant capacity and increased catalase and ceruloplasmin activities by 15-25% (p < 0.05). In contrast, higher doses-particularly of FEO-induced lipid peroxidation and protein oxidation by 40-60% (p < 0.05), indicating pro-oxidant behaviour. Erythrocyte haemolysis assays revealed that SEO exerted the strongest membrane-stabilising effect (haemolysis reduced by 18%), whereas FEO increased membrane fragility (haemolysis increased by 27%). CONCLUSION: Pinaceae-derived essential oils exhibit dual antioxidant and pro-oxidant activity dependent on concentration and species. Among them, PEO showed the most balanced redox profile. These findings highlight both the therapeutic potential and the importance of controlled dosing when considering such oils for biomedical applications.
Dietary Vitamin E Ameliorate Production Performance Via Pyruvate Metabolism Regulation in An Aged Laying Quails.
Chen H, Zou M, Cui T … +6 more , Qin X, Gao F, Deng S, Chen Z, Li Q, Wang Z
Cell Physiol Biochem · 2025 Nov · PMID 41342054 · Publisher ↗
BACKGROUND/AIMS: This study aimed to clarify the optimal amount of vitamin E required in the late stage of egg laying to explore the aging mechanism of the ovaries in this stage and the regulatory role of vitamin E in fe...
BACKGROUND/AIMS: This study aimed to clarify the optimal amount of vitamin E required in the late stage of egg laying to explore the aging mechanism of the ovaries in this stage and the regulatory role of vitamin E in female reproductive aging using multiple experimental methods and multiomics joint analysis. METHODS: The development of follicles was analyzed using Hematoxylin-eosin staining and terminal deoxynucleotidyl transferase deoxyuridine phosphate nick-end labeling staining. The content of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and Estradiol (E2) was determined by Enzyme-linked Immunoassay Kit. The activities of superoxide dismutase (SOD) and malondialdehyde (MDA) in the serum using enzyme-linked immunosorbent assay kits. RNA-seq and Untargeted metabolomics analyses were used to investigate the molecular mechanisms of vitamin E during ovarian aging. RESULTS: The findings revealed that quail reproductive organs rapidly aged at the 11th egg-laying month. Adding vitamin E to the diet significantly improved egg production performance. Vitamin E promoted the development of small yellow follicles by enhancing antioxidant capacity and inhibiting cell apoptosis. Furthermore, RNA-seq and LC-MS/MS identified genes and metabolites that may serve as biomarkers for vitamin E effects. CONCLUSION: Dietary supplementation with 250 mg/kg vitamin E enhanced energy metabolism, regulated SOD and MDA levels, reduced apoptosis, stimulated E2 secretion, promoted follicular development, and improved egg production performance.
Identifying Circ-RNF216 as a Regulator of Renal Tubular Epithelial Cell Proliferation Via the TGF-Β1/Smad3-Mediated Pathway in Chronic Kidney Disease.
Xu M, Yang Y, Zhang P … +3 more , Zhou C, Zhou Q, Luo N
Cell Physiol Biochem · 2025 Nov · PMID 41340590 · Publisher ↗
BACKGROUND/AIMS: Emerging evidence suggests that circular RNAs (circRNAs) play a crucial role in kidney disease regulation. However, their functional significance in chronic kidney disease (CKD) remains poorly understood...
BACKGROUND/AIMS: Emerging evidence suggests that circular RNAs (circRNAs) play a crucial role in kidney disease regulation. However, their functional significance in chronic kidney disease (CKD) remains poorly understood. METHODS: In this study, circRNAs were identified by RNA sequencing in two CKD mouse models, including unilateral ureteral obstruction (UUO) and anti-glomerular basement membrane (anti-GBM) glomerulonephritis. RNase-R treatment and Sanger sequencing were used to confirm circular structure. Circ-RNF216-shRNA was used to establish stable knockdown mTEC cell lines. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect circ-RNF216 expression. In situ hybridization was used to assess the expression and localization of circ-RNF216 in kidney. Transwell assays were performed to assess cell migration. RNA sequencing was performed to characterize mRNA expression profiles and identify pathways affected by circ-RNF216 knockdown in mTECs. RESULTS: We identified 1,589 circRNAs in two CKD mouse models. Circ-RNF216 expression was up-regulated in UUO models. Functional analyses revealed that circ-RNF216 regulates renal fibrosis through modulation of the TGF-β1/Smad3 pathway. Knocking down circ-RNF216 in mouse tubular epithelial cells led to significant suppression of migratory capacity and fibrosis. RNA sequencing showed that circ-RNF216 knockdown altered mRNA expression, with differentially expressed genes mainly enriched in the transforming growth factor-β receptor superfamily signaling pathway. CONCLUSION: Our findings highlight circ-RNF216 as a novel regulatory factor in CKD-related renal fibrosis, broadening our understanding of circRNA involvement in kidney disease pathogenesis and suggesting circ-RNF216 as a potential therapeutic target for preserving renal function.
Succinylation of CTBP1 Mediated by SIRT5 Suppresses MAT1A Expression to Promote the Progression of HCC.
Qiu Z, Wang Q, Li S … +2 more , Lu G, Han J
Cell Physiol Biochem · 2025 Nov · PMID 41340589 · Publisher ↗
BACKGROUND/AIMS: Succinylation, a recently characterized post-translational modification (PTM), is a ubiquitously occurring protein modification implicated in diverse biological processes via regulation of protein functi...
BACKGROUND/AIMS: Succinylation, a recently characterized post-translational modification (PTM), is a ubiquitously occurring protein modification implicated in diverse biological processes via regulation of protein function and gene expression. CTBP1 encodes C-terminal binding proteins and generates multiple splice variants. However, the functional significance of CTBP1 succinylation in hepatocellular carcinoma (HCC) remains unexplored. METHODS: Protein succinylation levels were quantified using immunoprecipitation coupled with Western blotting and mass spectrometry. Site-directed mutagenesis identified critical lysine residues targeted by succinylation. Functional impacts of CTBP1 succinylation on HCC cell behaviors were evaluated through CCK8-based cell viability, wound healing, transwell migration, and invasion assays. Molecular mechanisms were elucidated via qRT-PCR and Western blot analyses. RESULTS: Succinylation levels of CTBP1 were significantly elevated in HCC tumor tissues and cell lines relative to non-tumorous controls. Mass spectrometry and mutagenesis pinpointed K46 and K280 as the primary succinylation sites on CTBP1, with SIRT5 identified as the desuccinylase. Functionally, CTBP1 succinylation enhanced HCC cell proliferation, migration, and invasive potential. Mechanistically, this modification promoted tumor progression by suppressing MAT1A expression-a key regulator of hepatic differentiation and tumorigenesis. CONCLUSION: Our study reveals that SIRT5-mediated CTBP1 succinylation drives HCC progression through MAT1A suppression, establishing a novel regulatory axis with therapeutic potential for HCC treatment.
Identification of Novel Kv1.3 Channel-Interacting Proteins Using Proximity Labelling in T-Cells.
Kour D, Bowen CA, Srivastava U … +10 more , Nguyen HM, Kumari R, Kumar P, Brandelli AD, Bitarafan S, Tobin BR, Wood LB, Seyfried NT, Wulff H, Rangaraju S
Cell Physiol Biochem · 2025 Oct · PMID 41277224 · Full text
BACKGROUND/AIMS: Potassium channels regulate membrane potential, calcium flux, cellular activation and effector functions of adaptive and innate immune cells. The voltage-activated Kv1.3 channel is an important regulator...
BACKGROUND/AIMS: Potassium channels regulate membrane potential, calcium flux, cellular activation and effector functions of adaptive and innate immune cells. The voltage-activated Kv1.3 channel is an important regulator of T cell-mediated autoimmunity and microglia-mediated neuroinflammation. Kv1.3 channels, via protein-protein interactions, are localized with key immune proteins and pathways, enabling functional coupling between K+ efflux and immune mechanisms. METHODS: To gain insights into proteins and pathways that interact with Kv1.3 channels, we applied a proximity-labeling proteomics approach to characterize protein interactors of the Kv1.3 channel in activated T-cells. Biotin ligase TurboID was fused to either N or C termini of Kv1.3, stably expressed in Jurkat T cells, and biotinylated proteins in proximity to Kv1.3 were enriched and quantified by mass spectrometry. RESULTS: We identified over 1,800 Kv1.3 interactors including known interactors (beta-integrins, Stat1), although the majority were novel. We found that the N-terminus of Kv1.3 preferentially interacts with protein synthesis and protein trafficking machinery, while the C-terminus interacts with immune signaling and cell junction proteins. T-cell Kv1.3 interactors we found consisted of 335 cell surface proteins, including T-cell receptor complex, mitochondrial, calcium and cytokine-mediated signaling pathway, and lymphocyte migration proteins. 178 Kv1.3 interactors in T-cells also represent genetic risk factors for T cell-mediated autoimmunity, including STIM1, which was further validated using co-immunoprecipitation. CONCLUSION: Our studies revealed novel proteins and molecular pathways that interact with Kv1.3 channels in adaptive (T-cell) and innate (microglia) immune cells, providing a foundation for understanding how Kv1.3 channels may regulate immune mechanisms in autoimmune.
Tumor Destructive Mechanical Impulse (TMI) Treatment of Solid Tumors. Part I: Animal Experiments, Clinical Application and Immunological Abscopal Effect.
Theuer AE, Thomas I, Lang F … +4 more , Borkmann M, Mullins JD, Eigentler TK, Walter GF
Cell Physiol Biochem · 2025 Nov · PMID 41222217 · Publisher ↗
BACKGROUND/AIMS: The feasibility and effectiveness of Tumor Destructive Mechanical Impulse (TMI) treatment of solid tumors for standard clinical application is investigated. METHODS: Different solid tumors in a preparato...
BACKGROUND/AIMS: The feasibility and effectiveness of Tumor Destructive Mechanical Impulse (TMI) treatment of solid tumors for standard clinical application is investigated. METHODS: Different solid tumors in a preparatory animal experiment (VX2 head and neck squamous tumor) and in patients (malignant cutaneous melanoma and prostate carcinoma) are treated by TMI focused shock waves using patient-specific treatment parameters (total energy, energy flux density, shock wave frequency, total number and sequence of shock waves, the optimal placement of the treatment device) determined by multiple parametric simulations. RESULTS: In animal experiments and in the different treated tumor entities in several patients, the treated tumor or treated metastases regressed, and disguised tumor-associated antigens consistently initiated an immunological abscopal effect achieving that not only the directly treated primary tumor or a treated metastasis regressed but also untreated distant metastases. CONCLUSION: TMI treatment could have significant implications for the development of new effective and targeted regimens of cancer therapy.
Knee Joint Response to Mechanical Loading: Bounding Mechanotransduction with Rehabilitation.
Stańczak M, Swinnen B, Surmacz J … +4 more , Bielenda B, Febbi M, Trybulski R, Hagner-Derengowska M
Cell Physiol Biochem · 2025 Oct · PMID 41196605 · Publisher ↗
The knee joint is a weight-bearing structure that endures varied mechanical stresses in daily and athletic activities. Its cells convert these stresses into biochemical signals through mechanotransduction, prompting chan...
The knee joint is a weight-bearing structure that endures varied mechanical stresses in daily and athletic activities. Its cells convert these stresses into biochemical signals through mechanotransduction, prompting changes essential for joint health, repair, and adaptation. Understanding these processes is pivotal for developing rehabilitation strategies that address injuries and degenerative conditions like osteoarthritis. Different loading modalities-compression, tension, shear, and hydrostatic pressure-impact knee tissues (cartilage, synovium, ligaments, and tendons) and their resident cells (chondrocytes, synoviocytes, and fibroblasts). Chondrocytes adjust extracellular matrix synthesis to maintain cartilage integrity, while synoviocytes regulate synovial fluid components crucial for lubrication. Fibroblasts modulate collagen production, preserving ligament and tendon strength. Underlying these activities are key signaling pathways (e.g., MAPK, NF-κB, and Wnt) that regulate gene expression and cellular metabolism in response to mechanical stimuli. By linking basic mechanobiology insights to clinical practice, clinicians can tailor therapeutic interventions-such as controlled loading, exercise regimens, manual therapy, and orthotic devices-to optimize tissue repair, restore function, and prevent further degeneration. This mechanotransduction-focused approach offers a comprehensive framework for improving knee joint health and enhancing rehabilitation outcomes.
Epistemology of the Origin of Cancer III: Fundamentals of How Metastasis Arises.
Brücher BLDM, Jamall IS
Cell Physiol Biochem · 2025 Nov · PMID 41195695 · Publisher ↗
Metastasis, like carcinogenesis, involves the disruption of homeostasis such that cancer cells travel from the primary tumor to distant parts of the body. Almost all cancer deaths are due to metastatic spread. The prevai...
Metastasis, like carcinogenesis, involves the disruption of homeostasis such that cancer cells travel from the primary tumor to distant parts of the body. Almost all cancer deaths are due to metastatic spread. The prevailing theory of metastasis is an incomplete doctrine and far from sufficient as only 0.2% of free cancer cells result in the spread of cancer. To develop reasonable and effective cancer therapies and to prevent (or reverse) carcinogenesis and metastasis, a comprehensive understanding of how both carcinogenesis and metastasis arise is necessary. Fundamental questions in cancer biology have been asked and answered over decades of research: How do most cancers develop (Epistemology of the Origin of Cancer I, 2014-2022)? Which is the first cancer cell (II, 2023)? The third basic question in cancer biology remaining to be addressed is: What are the fundamentals of how metastasis develops? The pre-cancerous niche (PCN) that forms during carcinogenesis is altered by ongoing complex signaling into a premetastatic niche 1 (PMN-1): p130(cas)/crk/DOCK180 formation is necessary for lamellipodia formation, thereby enabling cell mobility. Cancer-associated fibroblasts (CAFs) begin to release fibronectin CXCL12 and Keratin 19. PMN-1 is transformed into PMN-2 during ongoing crosstalk and transformation of anti- into pro-tumorigenic platelets, macrophages, and neutrophils. Finally, persistent signaling and immune evasion result in the conversion of PMN-2 to PMN-3 with heterogeneous cancer satellites - the term "satellite" is used herein in accordance with its original meaning (a cell or particle escorting another). PMN-3 serves as a prerequisite for intravasation, traveling, and dissemination of cancer cells away from the primary tumor. Eight heterogeneous cancer satellites, including Trojan horses (immune evasion), travel alone or in combination: (1) cancer cells and (2) CAFs migrate along the CXCL12 and fibronectin gradient; (3) cancer cells surrounded by CAFs are shielded from the immune system and travel away from the primary cancer; (4) CXCL12 and Keratin 19 coat cancer cells; (5) platelets surround cancer cells and (6) CAFs, thereby facilitating cancer spread; and (7) neutrophil extracellular traps shield cancer cells and (8) CAFs. Metastasis in epithelial cancer occurs in parallel with carcinogenesis after the pre-cancerous niche is transformed into pre-metastatic niches (PMNs), which are indispensable to the origin of metastasis. Eight heterogeneous cancer satellites, including Trojan horses responsible for immune evasion, alongside reciprocally affecting sequences, wander alone or in conjunction with other cancer cells. This elucidates why the current practice of multimodal anti-cancer cell therapy should now be seen in a new light in which the benefits depend not on direct cancer cell effects, but on indirect cytopenic effects, which have previously been regarded merely as adverse effects.
B Cells at the Crossroads of Cardiovascular and Hematologic Disease: Paving the Way for Novel Immunomodulatory Therapies.
Choustoulaki A, Ben-Aicha S, Fotiou D … +4 more , Briasoulis A, Tsitsilonis O, Kastritis E, Nikolaou PE
Cell Physiol Biochem · 2025 Oct · PMID 41137618 · Publisher ↗
The interaction between the immune and cardiovascular systems is a growing field of investigation with bidirectional aspects. B cells are modulators of the adaptive and the innate immunity and they orchestrate bone marro...
The interaction between the immune and cardiovascular systems is a growing field of investigation with bidirectional aspects. B cells are modulators of the adaptive and the innate immunity and they orchestrate bone marrow and spleen immune responses beyond infectious diseases. B cell regulation contributes to the pathophysiology of myocardial damage in several conditions including myocardial infarction, heart failure and atherosclerosis. In parallel, B cell-derived hematological disorders are interlinked to cardiovascular complications, including thrombosis and immunoglobulin-related cardiotoxicity. The scope of this review is to summarize the function and role of B cells as important players in myocardial and vascular adaptations to injury and as mediators of cardiovascular adverse events in hematological disorders. The primary focus is to highlight the clinical and preclinical findings regarding B cell-targeted therapies and their positive or negative impact on the cardiovascular system. A deeper understanding of B cell subpopulations, functions, and secretome could lead to targeted therapeutic interventions for cardiovascular and hematologic diseases.
Epithelial Impermeability to Water: A Second Look.
Gibson LG, DeFilippo EK, Mahajan A … +1 more , Model MA
Cell Physiol Biochem · 2025 Oct · PMID 41137614 · Publisher ↗
Impermeability of the ascending limb of the Henle loop for water is traditionally regarded as essential for countercurrent multiplication in the kidney. Similar claims have been made about permeability properties of the...
Impermeability of the ascending limb of the Henle loop for water is traditionally regarded as essential for countercurrent multiplication in the kidney. Similar claims have been made about permeability properties of the collecting duct and some other epithelia. It is not clear, however, how a structure based on phospholipid bilayers can be water-impermeant if phospholipid bilayers themselves have measurable permeability. The presence of two membranes separated by the cytoplasm may only account for a several-fold reduction in permeability compared to a single bilayer. By analyzing published data, we conclude that these tubules do have a finite water permeability, especially the collecting duct. Although the results on isolated ascending limbs vary among authors, osmotic shock experiments clearly indicate that both the collecting duct and the ascending Henle loop are sufficiently water-permeable to observe volume regulation effects. We conclude that these epithelia by themselves do not display unusual resistance to water flow; it can be estimated that 20-50% of the fluid entering the tubules can be reabsorbed into a strongly hypertonic medulla. It is possible, however, that unstirred layers in the intact kidney may contribute to the apparent low permeability of the tubules.
SIRPα is An Inhibitory Receptor That Regulates NK Cell Activation and Function.
Cham LB, Hamdan TA, Bhat H … +4 more , Tabbara KS, Farid E, Barbouche MR, Adomati T
Cell Physiol Biochem · 2025 Sep · PMID 41047954 · Publisher ↗
BACKGROUND/AIMS: Signal regulatory protein alpha (SIRPα) is an inhibitory receptor expressed on macrophages and dendritic cells. Recent cancer research studies have reported evidence of upregulation of SIRPα on natural k...
BACKGROUND/AIMS: Signal regulatory protein alpha (SIRPα) is an inhibitory receptor expressed on macrophages and dendritic cells. Recent cancer research studies have reported evidence of upregulation of SIRPα on natural killer (NK) cells. The present study aimed to investigate the role of SIRPα in NK cells during viral infection. METHODS: We utilized SIRPα knockout mice (SIRPα-/-) and lymphocytic choriomeningitis virus (LCMV) infection to examine the role of SIRPα in NK cells. Flow cytometry, in vivo killing assays, and molecular analyses were performed to assess NK cell activation, cytotoxic function, and associated signaling pathways. RESULTS: SIRPα expression was induced on NK cells during LCMV infection. The absence of SIRPα in knockout mice resulted in an increased proportion and activation of NK cells, with enhanced expression of cytotoxic markers and augmented NK cell-mediated killing of target cells. Mechanistically, loss of SIRPα was associated with downregulation of Src homology region 2-containing protein tyrosine phosphatase-1 (SHP-1) in NK cells. Importantly, SIRPα deficiency led to concomitant loss of CD8+ T cells and impaired viral control. In vivo killing assays indicated that activated NK cells mediated CD8+ T cell depletion in SIRPα-/- mice. Experimental NK cell depletion in these mice partially restored T cell immunity, reduced immunopathology, and improved viral clearance. CONCLUSION: Our findings identify SIRPα as a critical inhibitory receptor that regulates NK cell effector functions. Loss of SIRPα unleashes NK cell activity but results in CD8+ T cell depletion and impaired antiviral immunity, highlighting the dual role of SIRPα in balancing NK cell activation and adaptive immune responses.
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