Cell Journal最新文献

{"title":"Liver Microarchitecture-Guided Design of Biomimetic Scaffolds: Biomaterials, Dynamic Culture Systems, and Emerging Clinical Translation: A Review.","authors":"Fatemeh Askari Yazdian, Zahra Barabadi, Masome Aghaei Lasboo, Matin Mojaveri Samak, Amirhossein Larijani, Parimehr Haidari, Mehraveh Mirzapour, Zohreh Hashemian, Massoud Vosough, Elham Vojoudi","doi":"10.22074/cellj.2026.2069129.1910","DOIUrl":"https://doi.org/10.22074/cellj.2026.2069129.1910","url":null,"abstract":"<p><p>Liver tissue engineering (TE) has emerged as a promising strategy to address the growing burden of liver disease and the shortage of donor organs, while also providing physiologically relevant <i>in vitro</i> models for drug development and disease research. This review synthesizes current knowledge on how native liver microarchitecture and extracellular matrix (ECM) organization can inform the rational design of liver-mimetic scaffolds. We first describe the hepatic acinus as the functional unit underlying metabolic zonation, highlighting regional differences in oxygen and nutrient gradients, cellular composition, and ECM specialization as key design cues for scaffold composition, stiffness, and spatial patterning. We then survey major classes of biomaterials, and discuss their physicochemical requirements and associated fabrication strategies. Particular attention is given to studies that have fabricated liver lobule or acinus-like architectures and to combinatorial strategies that integrate multiple fabrication methods with dynamic culture. Dynamic culture systems, including perfusion bioreactors and microfluidic liver-on-a-chip platforms, are examined as essential tools that provide physiological perfusion, controlled gradients, and mass transport to sustain hepatocyte function and metabolic zonation in engineered tissues. We further review organoid and lab-grown liver models, with emphasis on the self-organization processes by which stem cell-derived constructs recapitulate aspects of acinar architecture, and discuss their convergence with scaffold-based approaches as modular building blocks. Finally, we discuss the current status of clinical translation and commercialization, including the use of normothermic machine perfusion, and outline key scientific, manufacturing, cost, scalability, and regulatory challenges that must be addressed to achieve clinically applicable engineered liver tissues. We conclude that the convergence of acinar-inspired spatial design, liver-specific ECM biochemistry, physiological perfusion, and organoid-derived cell sources, supported by scalable, cost-effective manufacturing and clear regulatory pathways, will be essential to translate biomimetic liver constructs from laboratory prototypes to clinically applicable grafts and predictive <i>in vitro</i> models.</p>","PeriodicalId":49224,"journal":{"name":"Cell Journal","volume":"27 1","pages":"1-17"},"PeriodicalIF":1.7,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147718419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Role and Immunogenic Characteristics of Cancer Testis Antigens in Breast Cancer: A Review.","authors":"Motahareh Sheikh-Hosseini, Mostafa Neissi, Mohammad Moarefzadeh, Mahdieh Salimi, Azar Heidarizadi, Fateme Mohammadi-Asl","doi":"10.22074/cellj.2026.2044248.1703","DOIUrl":"https://doi.org/10.22074/cellj.2026.2044248.1703","url":null,"abstract":"<p><p>Breast cancer remains a leading cause of cancer-related deaths among women globally, presenting significant challenges due to its heterogeneity and complex biology. While traditional treatments such as surgery, chemotherapy, and targeted therapies offer some benefit, the lack of universal treatment strategies underscores the need for innovative approaches. A total of 255 articles were identified through PubMed, Scopus, Web of Science, and Google Scholar up to 1 December 2025, and 30 articles were selected for inclusion in this narrative review. This narrative review focuses on cancer-testis antigens (CTAs) as potential therapeutic targets in breast cancer. The objective of this narrative review is to evaluate the therapeutic role and immunogenic characteristics of CTAs in breast cancer, with emphasis on their potential in diagnosis, prognosis, and immunotherapy. CTAs are tumor-associated antigens that are aberrantly expressed in various cancers, including breast cancer, while their expression in normal tissues is restricted to the testis. Their unique immunogenic properties make them ideal candidates for both early diagnostic tools and targeted immunotherapy. This article discusses the potential of CTAs in improving breast cancer screening, prognosis, and treatment strategies, with particular emphasis on their roles in immunotherapy and vaccine development. Furthermore, the challenges of CTA-based treatments, including antigen heterogeneity and immune evasion, are outlined, along with insights into future research directions aimed at overcoming these obstacles and improving clinical outcomes.</p>","PeriodicalId":49224,"journal":{"name":"Cell Journal","volume":"27 1","pages":"1-13"},"PeriodicalIF":1.7,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147277540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spectrum and Clinical Correlates of Central Venous Line Complications in Pediatric Hematopoietic Stem Cell Transplantation Recipients: A Comparative Analysis of Infectious versus Non-Infectious Events in A Single-Center, Retrospective Study.","authors":"Niku Rahimi Afzl, Leily Mohajerzadeh, Sharareh Kamfar, Ali Reza Fahimzad, Reza Taherian, Nader Momtazmanesh, Zahra Khafaf, Masoud Alebouyeh, Javad Ghoroubi, Bibi Shahin Shamsian","doi":"10.22074/cellj.2026.2059832.1850","DOIUrl":"https://doi.org/10.22074/cellj.2026.2059832.1850","url":null,"abstract":"<p><strong>Objective: </strong>Central venous lines (CVLs) are indispensable in pediatric hematopoietic stem cell transplantation (HSCT) but carry a high risk of complications. This study aimed to compare the clinical, microbiological, and outcome profiles between pediatric HSCT recipients who developed infectious versus non-infectious CVL complications.</p><p><strong>Materials and methods: </strong>In this single-center, retrospective study, from a total of 228 pediatric HSCT recipients (2015-2024), this analysis focused on comparing the 76 patients who developed CVL-related infectious complications with the 74 patients who had non-infectious complications. Demographic, clinical, and transplant-related variables were analyzed. Bivariate analyses (Chi-square/Fisher's exact tests) were used to explore unadjusted associations between these variables and complication type.</p><p><strong>Results: </strong>In this study, infection was the most common complication (50.7% of all events). Patients with infectious complications more frequently had a non-malignant underlying disease (63.2% vs. 40.5%; OR=2.51, P=0.006) and had undergone allogeneic transplantation (89.5% vs. 58.1%; OR=6.33, P<0.001) compared to those with non-infectious complications. A higher proportion of patients with infectious complications had received a reduced-intensity conditioning (RIC) regimen (48.7% vs. 32.4%), although this difference did not reach statistical significance after multiple-comparison adjustment (P=0.031).</p><p><strong>Conclusion: </strong>This within-group comparative study characterizes a subgroup of pediatric HSCT recipients with infectious CVL complications, defined by non-malignant underlying disease, allogeneic transplantation, and RIC. These exploratory findings describe clinically relevant patterns among complicated cases and provide a hypothesis-generating basis for future analytical studies to investigate causal risk factors.</p>","PeriodicalId":49224,"journal":{"name":"Cell Journal","volume":"27 1","pages":"1-9"},"PeriodicalIF":1.7,"publicationDate":"2026-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147272603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cystathionine Enzymes in Transsulfuration and HO-1 Production: Impact on Spermatogenic Disorders in Folate and B12 Deficient Mice.","authors":"Nafise Zamani, Marziyeh Tavalaee, Zahra Mohammadi, Farzaneh Rabiee, Mohammad Hossein Nasr-Esfahani","doi":"10.22074/cellj.2026.2057175.1822","DOIUrl":"https://doi.org/10.22074/cellj.2026.2057175.1822","url":null,"abstract":"<p><strong>Objective: </strong>The 1-carbon metabolic cycle is essential for cellular growth, biomolecule synthesis, and epigenetic regulation. This cycle depends on B-complex vitamins, particularly folate (B9) and cobalamin (B12), which act as cofactors. Deficiencies in these vitamins can disrupt homocysteine metabolism, impair spermatogenesis, and increase oxidative stress, thereby compromising male fertility. To investigate the impact of dietary deficiencies in vitamins B12 and B9 on trans-sulfuration enzymes [cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE)], sperm function, oxidative stress, and DNA methylation in a mouse model.</p><p><strong>Materials and methods: </strong>In this experimental study, male mice were fed either a standard chow diet or a diet deficient in vitamins B12 and B9. Sperm parameters, chromatin integrity [via acridine orange (AO) and aniline blue (AB)], lipid peroxidation, and intracellular reactive oxygen species (ROS; assessed using DCFH-DA and BODIPY C11) were evaluated. Sperm DNA methylation was measured using immunofluorescence. Serum levels of folate, vitamin B12, and testosterone were quantified. Expression of <i>CBS, CSE,</i> and <i>HO-1</i> were analyzed by quantitative reverse transcriptase polymerase chain reaction (qRTPCR) and Western blot.</p><p><strong>Results: </strong>Mice on the vitamin B deficient (VBD) exhibited significantly decreased sperm concentration and motility, along with increased morphological abnormalities, DNA damage, histone retention, and lipid peroxidation. Intracellular ROS levels did not differ significantly from controls. The VBD group also showed lower serum folate and B12, elevated homocysteine, and reduced testosterone levels. DNA methylation intensity in sperm was significantly decreased. Histological analysis revealed impaired testicular architecture and reduced spermatogenic indices. CSE gene expression was significantly downregulated, whereas CBS and Heme oxygenase 1 (HO-1) expression remained unchanged. Protein levels of CBS, CSE, and HO-1 showed no significant differences.</p><p><strong>Conclusion: </strong>Deficiencies in folate and vitamin B12 negatively affect sperm quality and testicular function in male mice, likely through disrupted homocysteine metabolism and altered gene expression in the trans-sulfuration pathway. These findings underscore the importance of adequate B-vitamin intake for male reproductive health.</p>","PeriodicalId":49224,"journal":{"name":"Cell Journal","volume":"27 1","pages":"1-9"},"PeriodicalIF":1.7,"publicationDate":"2026-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147272644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and Genetic Analysis of Limb-Girdle Muscular Dystrophy Type 2F with A Novel <i>SGCD</i> Mutation: A Case Report.","authors":"Amin Sakhaei, Javad Mohammadi-Asl","doi":"10.22074/cellj.2025.2044959.1707","DOIUrl":"https://doi.org/10.22074/cellj.2025.2044959.1707","url":null,"abstract":"<p><p>Limb-girdle muscular dystrophies (LGMDs) represent a varied group of genetic disorders characterised by the progressive weakening and atrophy of proximal muscles, particularly those in the shoulders and hips. These conditions are inherited in either an autosomal dominant or recessive pattern, with numerous genes implicated in their pathogenesis. Clinically, LGMDs are marked by a gradual decline in muscle function, often resulting in significant mobility impairments. In this study, we identify and characterise a novel homozygous deletion mutation, c.572_574delTAA, in the <i>SGCD</i> gene in a consanguineous Iranian family affected by LGMD2F. The patient, a 10.5-year-old boy, exhibited progressive muscle weakness alongside specific clinical features such as contractures and scoliosis. Genetic analysis revealed that this deletion caused a p.Leu191del alteration in the δ-sarcoglycan protein. The mutation was confirmed via Sanger sequencing and found to co-segregate with the disease phenotype within the family. These findings provide new insights into the genetic basis of LGMD2F, underscoring the critical role of comprehensive genetic analysis for accurate diagnosis and management. This study contributes to the broader understanding of the genetic diversity of LGMDs and highlights the need for ongoing research to enhance diagnostic and therapeutic approaches.</p>","PeriodicalId":49224,"journal":{"name":"Cell Journal","volume":"27 1","pages":"1-10"},"PeriodicalIF":1.7,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146259825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifunctional Alginate-Gelatin Scaffolds Containing Cerium-Doped Bioactive Glass for Potential Bone Regeneration: Physicochemical, Antioxidant, and Antibacterial Evaluations.","authors":"Fatemeh Shams, Nafiseh Baheiraei, Masoomeh Shams-Ghahfarokhi","doi":"10.22074/cellj.2025.2058530.1837","DOIUrl":"https://doi.org/10.22074/cellj.2025.2058530.1837","url":null,"abstract":"<p><strong>Objective: </strong>RScaffolds incorporating bioactive glass (BG) have shown significant potential in promoting bone tissue repair. Cerium (Ce)-doped 45S5 BG (BG/Ce), in particular, offers therapeutic benefits by enhancing osteoblast proliferation and differentiation, as well as providing antimicrobial and antioxidant effects. This study aimed to evaluate the effects of incorporating BG/Ce into alginate-gelatin (ALG-GEL) scaffolds at varying concentrations (5, 10, and 15% w/v), focusing on their physicochemical, biological, antimicrobial, and antioxidant properties to identify the optimal scaffold composition.</p><p><strong>Materials and methods: </strong>In this experimental study, BG and Ce-doped BG were synthesized and characterized. ALG-GEL, ALG-GEL-BG, and ALG-GEL-BG/Ce scaffolds were fabricated at varying concentrations and subjected to physicochemical analyses. Cytotoxicity was evaluated using an MTT assay at 48 and 72 hours, while cell morphology was examined by scanning electron microscopy (SEM). The antimicrobial activity of selected scaffolds (ALG-GEL, ALG-GEL-BG 10%, and ALGGEL- BG/Ce 10%) was assessed via optical density measurements at 620 nm (OD-620), field emission SEM (FE-SEM), and disk diffusion tests. Antioxidant capacity was determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay.</p><p><strong>Results: </strong>Incorporation of BG/Ce markedly increased the Young's modulus of the scaffolds, from 14.1 ± 0.98 MPa for ALG-GEL to 90.07 ± 2.7 MPa for ALG-GEL-BG/Ce 10%. The MTT assay revealed enhanced viability and adhesion of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) on ALG-GEL-BG/Ce scaffolds at 48 and 72 hours. Antimicrobial assessments, including OD620 measurements, FE-SEM imaging, and disk diffusion tests, demonstrated superior antibacterial activity of the ALG-GEL-BG/Ce 10% scaffold against <i>Escherichia coli</i> and <i>Staphylococcus aureus</i> compared to its Ce-free counterpart. Furthermore, the ALG-GEL-BG/Ce 10% scaffold exhibited notable antioxidant activity.</p><p><strong>Conclusion: </strong>The ALG-GEL-BG/Ce scaffold demonstrates enhanced physicochemical, antibacterial, and antioxidant properties, highlighting its potential as a novel biomaterial for bone regeneration applications.</p>","PeriodicalId":49224,"journal":{"name":"Cell Journal","volume":"27 1","pages":"1-14"},"PeriodicalIF":1.7,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146259864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Potential of Quercetin on A Rat Model of Radiation-Induced Brain Neurotoxicities: Insights from Behavioural and Biochemical Analyses.","authors":"Daryoush Moslemi, Fatemeh Khani, Fereshteh Pourabdolhossein, Sohrab Kazemi, Seyed-Mohammad Hosseini, Ali-Akbar Moghadamnia, Danial Sarrut, Manouchehr Ashrafpour","doi":"10.22074/cellj.2025.2046460.1730","DOIUrl":"https://doi.org/10.22074/cellj.2025.2046460.1730","url":null,"abstract":"<p><strong>Objective: </strong>Radiation therapy (RT), while effective for cancer, can cause significant neurotoxicity. This study evaluated the neuroprotective potential of quercetin against radiation-induced brain injury (RIBI) in an adult male Wistar rat model.</p><p><strong>Materials and methods: </strong>In this experimental study, 42 adult male rats were randomised into control, RT, RT+vehicle (Tween), and RT+quercetin (2.5, 5, or 10 mg/kg) groups. The RT-treated animals received eight fractions of 40 Gy cranial radiation. Quercetin was administered daily for four weeks in the appropriate groups. Spatial memory was assessed via the Morris water maze (MWM) test. Serum biomarkers of tumour necrosis factor-α (TNF-α), IL-2, ferric reducing antioxidant power (FRAP), malondialdehyde (MDA), and hippocampal histopathology [cornu ammonis (CA1), dentate gyrus (DG)] were analysed.</p><p><strong>Results: </strong>RT significantly impaired spatial learning. This deficit was significantly ameliorated by all tested quercetin doses during the training trials. RT induced a marked increase in serum TNF-α levels, from a baseline of 113.8 ± 19.4 ng/L in the control group to 257.8 ± 28.8 ng/L (P=0.005). Quercetin treatment effectively reversed this proinflammatory response by significantly reducing TNF-α concentrations at all administered doses. The 2.5 mg/kg dose reduced levels to 121.7 ± 19.5 ng/L (P=0.008). A key finding was the potent effect of the 5 mg/kg dose on oxidative damage, as it produced the most significant reduction in MDA levels compared to the RT group. Histological analysis showed that quercetin enhanced neuronal survival; the 2.5 and 5 mg/kg doses significantly increased neuronal counts in the hippocampal CA1 and DG regions.</p><p><strong>Conclusion: </strong>The Quercetin exhibited a protective effect against radiation-induced neurotoxicity in the adult male Wistar rats by improving behavioural, biochemical, and histological outcomes. The 5 mg/kg dose provided the most consistent benefit. These findings suggest that quercetin, particularly at 5 mg/kg, could serve as a potential adjunctive therapy to mitigate neurotoxic side effects associated with RT.</p>","PeriodicalId":49224,"journal":{"name":"Cell Journal","volume":"27 1","pages":"1-11"},"PeriodicalIF":1.7,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146258853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Sulfated Alginate-Cerium Bioactive Glass Scaffolds: Promising Platform for Cardiac Tissue Regeneration.","authors":"Fatemeh Forouzandeh, Abdullah Aldhaher, Nafiseh Baheiraei, Fatemeh Shams, Ali Doostmohammadi, Heshmat Allah Samimi","doi":"10.22074/cellj.2025.2059774.1851","DOIUrl":"https://doi.org/10.22074/cellj.2025.2059774.1851","url":null,"abstract":"<p><strong>Objective: </strong>Cardiovascular diseases remain a leading cause of global mortality and morbidity, despite advances in prevention, diagnosis, and treatment. Cardiac tissue engineering (CTE) offers a promising approach to repairing damaged myocardium through bioengineered constructs that closely mimic native cardiac tissue. The integration of biomaterials that enhance angiogenesis, exhibit antioxidant activity, and support cellular proliferation can further improve regenerative outcomes. This study aimed to assess the potential of a sulfated alginate (S-Alg)/cerium-doped 45S5 bioactive glass (Ce-BG) scaffold as a cardiac patch for tissue engineering applications.</p><p><strong>Materials and methods: </strong>In this experimental study, novel porous scaffolds composed of S-Alg and Ce-BG were fabricated using a freeze-drying technique. The scaffolds underwent comprehensive physicochemical characterization and cytocompatibility evaluation. Their angiogenic potential was assessed by quantifying vascular endothelial growth factor receptor 2 (VEGFR2) expression using quantitative reverse transcription polymerase chain reaction (qRT-PCR) over a seven-day period. Additionally, scaffold antioxidant activity was assessed using the DPPH assay.</p><p><strong>Results: </strong>Scanning electron microscopy (SEM) revealed an interconnected porous network with an average pore diameter of 100-300 μm. Incorporation of BG particles led to a reduction in tensile strength and Young's modulus. The ion release profile demonstrated sustained release of bioactive ions. MTT assays and cell morphology analyses confirmed scaffold cytocompatibility, supporting adhesion and proliferation of human umbilical vein endothelial cells (HUVECs). qRT-PCR showed significant upregulation of <i>VEGFR2</i> in HUVECs cultured on Ce-containing scaffolds over seven days. Moreover, the addition of Ce enhanced the antioxidant activity of BG-containing scaffolds, effectively scavenging DPPH radicals over time, highlighting their potential for cardiac patch applications.</p><p><strong>Conclusion: </strong>The S-Alg/Ce-BG composite scaffold exhibits favorable properties for CTE, including cytocompatibility, enhanced angiogenic potential, and antioxidant activity. These features highlight the scaffold as a highly promising candidate for advancing cardiac tissue regeneration strategies.</p>","PeriodicalId":49224,"journal":{"name":"Cell Journal","volume":"27 1","pages":"1-12"},"PeriodicalIF":1.7,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146203509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Anti-proliferative and Pro-apoptotic Effects of Iranian Viper Venom (<i>Vipera raddei kurdistanica</i>) on Human Gastric Cancer Cells (C615) are Mediated by PI3K/AKT/mTOR Signalling Pathway Inhibition.","authors":"Cyrus Jalili, Mona Pazhouhi, Mohammadreza Gholami, Fuzieh Khani-Hemmatabadi, Keyvan Maleki","doi":"10.22074/cellj.2026.2061544.1869","DOIUrl":"https://doi.org/10.22074/cellj.2026.2061544.1869","url":null,"abstract":"<p><strong>Objective: </strong>Gastric cancer (GC) is one of the most common malignancies worldwide. Since the PI3K/AKT/mTOR signalling pathway plays a crucial role in tumour growth and survival, this study aims to evaluate the anti-proliferative and pro-apoptotic effects of <i>Vipera raddei kurdistanica</i> venom on human GC cells (C615).</p><p><strong>Materials and methods: </strong>In this an experimental study, C615 cancer cells and normal fibroblasts were treated with 0.63-10 μg/ml of venom for 24, 48, 72, and 96 hours. Cell viability was analysed using MTT and trypan blue staining, and cytotoxicity was assessed by the lactate dehydrogenase (LDH) assay. Apoptosis at the half-maximal inhibitory concentration (IC₅₀) concentration was evaluated using the TUNEL, annexin V/PI flow cytometry, and diphenylamine DNA fragmentation assays. Mitochondrial membrane potential (JC-1), cytosolic cytochrome c levels, and the expressions of apoptosis-related and PI3K/ AKT/mTOR pathway genes were measured. All experiments were performed in three independent biological replicates.</p><p><strong>Results: </strong>Venom treatment significantly reduced cell viability in a time- and concentration-dependent manner. The IC₅₀ values in fibroblasts being approximately 51-59-fold higher than in C615 cells across time points. At the IC50 dose, venom treatment produced a very large effect on apoptosis induction, increasing early and late apoptosis by approximately 84-fold and 463-fold, respectively, compared with controls. DNA fragmentation (15.7-fold) were significantly elevated (P<0.001). Venom exposure exerted a reducing effect on mitochondrial membrane potential (37%, P=0.032) and increased cytochrome c release (2.31-fold, P=0.001). Gene expression analysis showed upregulation of <i>FAS</i> (1.67-fold; P<0.001), <i>FASL</i> (1.28 fold; P=0.005), <i>BAX</i> (2.34 fold; P<0.001), <i>BAK</i> (1.29 fold; P=0.004), and <i>BIM</i> (1.4 fold; P<0.001) and downregulation of <i>BCL-2</i> (0.44 fold; P<0.001), <i>BCL-XL</i> (0.47 fold; P<0.001), <i>PI3K</i> (P<0.001), <i>AKT</i> (P<0.001), and <i>MTOR</i> (P<0.001).</p><p><strong>Conclusion: </strong><i>Vipera raddei kurdistanica</i> venom may exert selective cytotoxic effects against gastric cancer cells and may induce apoptosis through both intrinsic and extrinsic pathways, potentially via inhibition of the PI3K/AKT/mTOR signalling axis.</p>","PeriodicalId":49224,"journal":{"name":"Cell Journal","volume":"27 1","pages":"1-9"},"PeriodicalIF":1.7,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146203500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise Training Modulates TLR4/NF-κB-Mediated Inflammatory Signaling in Rat Testes after Tramadol Withdrawal.","authors":"Adel Ahmadyzad, Asghar Tofighi, Javad Tolouei Azar, Mazdak Razi","doi":"10.22074/cellj.2025.2046681.1734","DOIUrl":"https://doi.org/10.22074/cellj.2025.2046681.1734","url":null,"abstract":"<p><strong>Objective: </strong>Chronic tramadol (TRA) exposure has been reported to induce inflammatory responses in testicular tissue, whereas exercise training exerts immunomodulatory effects within the testes. Accordingly, this study investigated whether exercise training protocols (ETPs) during the post-withdrawal period modulate testicular inflammation via the TLR4/NF-κB-mediated inflammatory signaling pathway.</p><p><strong>Materials and methods: </strong>In this experimental study, adult Wistar rats (n=36; sex: male; age: 8 weeks; body weight: 180-220 g) were randomly assigned to a control group and tramadol-treated groups. The control group received normal saline. TRA was administered at a dose of 40 mg/kg, via intraperitoneal route, for 60 days. TRA withdrawal was induced by stopping TRA administration after 60 days and maintained for an additional 60 days. Following withdrawal, tramadol-exposed rats were allocated to a withdrawal-only group or to low-, moderate-, or high-intensity continuous exercise training groups. At the end of the experimental period, testicular tissue samples were collected. The expression or levels of IL-6, IL-10, COX-II, TLR4, NF-κB, TNF-α, and iNOS parameters were evaluated using quantitative reverse transcription polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, immunofluorescence staining, and Western blotting methods.</p><p><strong>Results: </strong>The TRA administration increased the expression of TLR4, NF-κB, IL-6, and TNF-α. These elevations were reduced after withdrawal and were more markedly attenuated in exercise-trained groups. IL-10 levels were decreased in the tramadol-only group but were restored during withdrawal with exercise training. TRA exposure was associated with increased numbers of iNOS+ and COX-II+ somatic and germ cells; these alterations were reversed after withdrawal, particularly in exercised animals. Despite TRA cessation, residual immune dysregulation persisted, characterized by elevated TLR4, NF-κB, IL-6, and TNF-α expression.</p><p><strong>Conclusion: </strong>Exercise training following TRA withdrawal could restore inflammatory balance by suppressing TLR4 and NF-ΚB signaling, normalizing pro- and anti-inflammatory cytokine profiles, and possibly attenuating the iNOS/NO/COXII pathway in Wistar rats.</p>","PeriodicalId":49224,"journal":{"name":"Cell Journal","volume":"27 1","pages":"1-14"},"PeriodicalIF":1.7,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146203592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}