Cells最新文献

{"title":"Adenosine-A2 Receptor Signaling in Astrocytes Mitigates Cerebral Ischemic Injury via Suppressing Glutamate-Induced Excitotoxicity.","authors":"Cheng Yuan, Jixin Chen, Yazhi Chen, Liyuan Cui, Yingjiao Liu","doi":"10.3390/cells15201915","DOIUrl":"10.3390/cells15201915","url":null,"abstract":"<p><p>Excitotoxicity constitutes a core pathological mechanism in cerebral ischemia and other central nervous system disorders. Astrocytes serve as pivotal regulators of glutamate-glutamine cycle homeostasis and thereby play a critical role in mitigating excitotoxicity. This study established a rat thromboembolic stroke model via autologous thrombus induction and systematically investigated the mechanisms underlying adenosine-mediated neuroprotection through pharmacological modulation of the adenosine pathway using adenosine, dipyridamole, and selective adenosine receptor antagonists. Subsequently, light-sensitive opsin expression in astrocytes was driven by the GFAP promoter, enabling cell-type-specific optogenetic modulation of astrocyte activity. Our findings demonstrate that adenosine significantly attenuates cerebral injury in a rat model of thromboembolic stroke, with astrocytes identified as the primary cellular target. Adenosine elicits an anti-excitotoxic effect by coordinately upregulating GLT-1 protein expression and downregulating Cx43 protein expression in astrocytes, thereby regulating glutamate transport and diffusion. Moreover, our findings demonstrate that adenosine-mediated neuroprotection is significantly attenuated by SCH58261 but not by PSB1115. We conclude that the adenosine-A_2A receptor system plays a critical role in the regulation of glutamate homeostasis.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 20","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13703560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149263347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Papillomavirus (HPV) Infection-Associated Epithelial-to-Mesenchymal Transition: Implication in Tumorigenesis and Pathogenesis of HPV-Positive Cancers.","authors":"Alexander E Kabakov, Olga N Matchuk, Anna V Khokhlova, Andrey D Kaprin","doi":"10.3390/cells15201916","DOIUrl":"10.3390/cells15201916","url":null,"abstract":"<p><p>Epithelial-to-mesenchymal transition (EMT) is a programmed and reversible process that allows epithelial cells to temporarily acquire a mesenchymal cell phenotype with increased migratory and invasive capacity. Analogous phenotypic modulation can also occur in carcinoma cells, which, after undergoing EMT, exhibit cancer stem cell-like properties and actively migrate, leading to tumor invasion and metastases. This structured narrative review focuses on the molecular crosstalk between human papillomavirus (HPV) and EMT, which occurs in HPV-infected human epithelium and in HPV-positive cancers of different location (cervical, head and neck, colorectal, lung, and others). The main questions addressed here are: (i) how HPV-driven EMT may contribute to the malignant transformation of HPV-infected epithelial cells, (ii) what mechanistic links may exist between the HPV positivity and EMT in human cancers, and (iii) how EMT in various HPV-positive human tumors may influence their pathogenesis, treatment modalities and outcomes. The relationship between HPV infection and EMT program is delineated as a complex multicomponent mechanism triggered by exogenous and endogenous stimuli and involving specific ligand-receptor interactions, membrane channels, transcription factors, signaling pathways, epigenetic regulators, etc. The review also discusses some of the potential applications of EMT-related biomarkers and molecular targets in the prevention, prediction and treatment of HPV-induced cancers.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 20","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13703920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149263419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytokine-Mediated Plasticity in the Molecular Requirements for Peptide-Loading Complex Formation and Antigen Presentation.","authors":"Ritchlynn Aranha, Mohadeseh Dastpeyman, Kirti Pandey, Mohammadreza Dorvash, Rochelle Ayala, Nathan P Croft, Anthony W Purcell","doi":"10.3390/cells15201914","DOIUrl":"10.3390/cells15201914","url":null,"abstract":"<p><p>HLA class I antigen presentation depends on coordinated peptide processing, transport and loading, yet inflammatory signalling may modify the consequences of defects in this machinery. We examined wild-type HAP1 cells and isogenic ERAP1-, TAP1- and TAP2-knockout cells before and after interferon-γ (IFNγ) treatment using flow cytometry, proteomics, and immunopeptidomics. IFNγ strongly induced residual antigen-processing machinery in all HAP1-genotypes, increased HLA-I surface expression and expanded peptide recovery, including peptides derived from cancer-associated antigens. However, repertoire restoration was incomplete and defect-specific. ERAP1-deficient cells retained enrichment of longer, terminally extended peptides, whereas TAP2-deficient cells retained alterations in peptide length, processing of peptide flanking regions and source-protein location of the peptide. TAP1-deficient cells showed the greatest convergence to wards wild-type immunopeptidome features upon IFNγ stimulation. Components of the peptide-loading and ER quality-control machinery remained associated with immature HLA-I heavy chains in TAP-deficient cells and were enhanced by exposure to IFNγ. These findings demonstrate that inflammatory signalling can quantitatively and partially qualitatively compensate for defects in HLA-I antigen processing by amplifying intact pathway components and alternative peptide supply, without recreating a fully wild-type immunopeptidome.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 20","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13703434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149263314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recurrent Corneal Erosion Syndrome in Epithelial Basement Membrane Dystrophy: Current Treatments and Mechanism-Guided Therapeutic Opportunities.","authors":"Sujin Kang, Alfonso L Sabater, Sotiria Palioura, Sonia H Yoo","doi":"10.3390/cells15201912","DOIUrl":"10.3390/cells15201912","url":null,"abstract":"<p><p>Recurrent corneal erosion syndrome (RCES) and epithelial basement membrane dystrophy (EBMD), also termed anterior basement membrane dystrophy, are distinct entities. RCES most often follows shearing corneal trauma, whereas EBMD may be asymptomatic, may blur vision without pain, or may predispose to erosions through defective epithelial attachment. This narrative review focuses on RCES associated with EBMD. It emphasizes how treatment choice depends on clinical findings, on whether the main goal is pain control, recurrence prevention, or visual rehabilitation, and on how directly the evidence applies to EBMD rather than to mixed-cause erosions. Lubrication and bandage lenses protect the healing surface, while anti-inflammatory and blood-derived therapies support repair. Debridement removes unstable epithelium; manual superficial keratectomy, diamond burr polishing, alcohol delamination, and phototherapeutic keratectomy treat the abnormal interface. Anterior stromal puncture provides focal scar-mediated anchoring, principally outside the visual axis. Contemporary procedural studies support individualized treatment but do not establish a universally superior technique. A heparan sulfate mimetic polymer has been tested directly in EBMD, but only in one small uncontrolled series; topical insulin, neurotrophic treatments, and differentiation-related targets lack EBMD-specific evidence of benefit. Epithelial closure, prevention of painful erosions, and optical rehabilitation are distinct outcomes and should not be treated as interchangeable measures of success. Management of EBMD-associated RCES should therefore be guided by the dominant clinical problem, lesion location, and the specific therapeutic outcome sought.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 20","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13703213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149263378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteochondral Cell Fate in the Mandibular Condyle: A Shared Fate Decision Across Development, Degeneration, and Regeneration.","authors":"Lingfeng Xu, Meiqing Wang","doi":"10.3390/cells15201913","DOIUrl":"10.3390/cells15201913","url":null,"abstract":"<p><p>The mandibular condyle is highly responsive to mechanical loading, which shapes its development and maintains osteochondral homeostasis. Understanding how loading regulates osteochondral cell fate may connect developmental mechanisms with strategies to limit mechanically driven degeneration and promote repair. In this narrative review, we integrate evidence across development, degeneration, and regeneration into a framework centred on a shared cell-fate decision: coordination between progenitor renewal, chondrocyte maturation, and endochondral bone formation. We examine the reported dual modes of parathyroid hormone-related protein (PTHrP) signalling and their interactions with Indian hedgehog (IHH) and canonical Wnt/β-catenin signalling within the broader network governing this balance. Physiological loading supports the spatial and temporal coordination of these pathways, whereas persistent abnormal loading may accelerate hypertrophic differentiation and impair progenitor replenishment, contributing to cartilage damage and aberrant osteochondral remodelling. Effective regeneration may therefore depend on restoring both a favourable mechanical environment and coordinated cell-fate regulation. Accordingly, where pathological occlusal loading contributes to degeneration, correcting the mechanical environment may merit consideration alongside biological interventions tailored to the joint's residual repair capacity. Potential approaches include pathway modulation to support responsive endogenous cells and cell supplementation when progenitor reserves are insufficient.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 20","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13703775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149263402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bet v 1 Allergen Is the Main Driver of Disease in Patients with Pollen Allergy in Belgium.","authors":"Françoise Pirson, Esmeralda Fraille Lopez, Cloé Hupin, Carine Sohy, Bertrand Bearzatto, Marylène Lecocq, Charles Pilette","doi":"10.3390/cells15201907","DOIUrl":"10.3390/cells15201907","url":null,"abstract":"<p><p>Birch pollen-sensitized patients co-sensitized to Bet v 1 and Bet v 2 allergens present more frequent and severe respiratory or plant-related food allergy symptoms (PFASs). This study analyzed the relevance of Bet v 1 and profilin sensitization in the clinical phenotype of pollen-allergic patients in Belgium. Ten patients allergic to birch pollen (BPA), 31 to grass pollen (GPA) and 33 to both pollens (MPA), with rhino-conjunctivitis with/without asthma (ARRC), were evaluated by means of questionnaire, skin-prick tests and specific IgE assays. Half of GPA were co-sensitized to birch pollen, and no BPA were sensitized to profilin. The prevalence of asthma and pollen-related food allergy syndrome (PFAS) was higher in BPA than in MPA or GPA, with a higher severity of PFAS in asthmatic BPA. GPA with PFAS were more frequently sensitized to Bet v 1, with higher levels of rBet v 1-IgE. The prevalence of PFAS, together with the duration of rhinitis and PFAS tended to increase in profilin-polysensitized vs. mono- and un-sensitized GPA, regardless of Bet v 1-IgE and the severity of symptoms.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 20","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13703822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149263288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperglycemia-Induced Loss of Astrocytic Kir4.1 Is Associated with Increased DNMT1 Activity and Altered AMPK/SIRT1 Signaling.","authors":"Jadier Colón-Vázquez, Yanitza Hernández-Santiago, Christian J Malpica-Nieves, Nathaly M Rosado-Rivera, Joshua J Navedo-Jackson, Arelys A Angueira-Laureano, Miguel P Méndez-González, Yuriy Kucheryavykh, Misty J Eaton, Serguei N Skatchkov, David E Rivera-Aponte","doi":"10.3390/cells15201906","DOIUrl":"10.3390/cells15201906","url":null,"abstract":"<p><p>The effects of chronic hyperglycemia on CNS, glial homeostasis and Kir4.1 regulation is poorly understood. Elevated blood glucose levels affect polyamine-sensitive inwardly rectifying potassium channels, Kir4.1, in astrocytes and retinal Müller glial cells. These cells regulate extracellular potassium and clear glutamate, processes supported by Kir4.1. Dysregulation of Kir4.1 channels has been implicated in glutamate toxicity, epilepsy, ataxia, and diabetes-induced neurodegeneration. In this study, we used Tandem Mass Tag Proteomic analysis, Pyrosequencing, SDS-PAGE and Western blot analysis, in whole brain and astrocytic primary cultures in hyperglycemic conditions testing DNMT1 and AMPK activities with RG-108, compound C, and AICAR treatments to investigate how hyperglycemia alters Kir4.1 expression in astrocytes and explored two regulatory mechanisms: (i) DNA methylation mediated by DNA methyltransferase 1 (DNMT-1), which uses S-adenosylmethionine (SAM) as a methyl donor, and (ii) metabolic signaling via the AMPK/SIRT-1 cascade. We found that hyperglycemia (25 mM glucose) (i) increased DNMT-1 protein levels in astrocytes by 1.5-2-fold and (ii) decreased AMPK and (iii) SIRT-1 levels, accompanied by a reduction in Kir4.1 protein expression. Pharmacological inhibition of DNMT-1 with RG-108 decreased DNMT-1 levels and restored Kir4.1. Treatment with AICAR, a selective AMPK activator, rescued SIRT-1 and Kir4.1 expression. In summary, hyperglycemia engages dual regulatory pathways: (i) epigenetic via DNMT-1 and (ii) metabolic via AMPK/SIRT-1, which converge on Kir4.1 downregulation in astrocytes. Therefore, both DNMT-1 inhibition and AMPK activation rescued Kir4.1 expression, suggesting functional support for potassium and glutamate homeostasis and membrane potential stability in glia.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 20","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13702995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149263436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin-Induced Vacuolizing Stress Reveals a Vulnerability Associated with NF1 Loss in Schwann Cells.","authors":"Assunta Maria Iazzetta, Francesca Sardina, Cinzia Rinaldo","doi":"10.3390/cells15201904","DOIUrl":"10.3390/cells15201904","url":null,"abstract":"<p><p>Neurofibromatosis type 1 (NF1) predisposes to peripheral nerve sheath tumors arising from Schwann-lineage cells with biallelic NF1 loss and remains in need of biologically informed strategies compatible with chronic disease management. Curcumin has attracted interest in NF1, but its effects in disease-relevant cells remain unclear. Here, we investigated curcumin responses in patient-derived NF1-deficient Schwann cells. Curcumin induced the progressive accumulation of cytoplasmic vacuoles resembling those elicited by a reference methuosis inducer, without prominent evidence of canonical apoptotic features. Vacuolization was associated with impaired long-term clonogenic recovery, indicating a durable loss of proliferative fitness. NF1-deficient Schwann cells displayed lower levels of NRF2, thioredoxin, and SOD1 than NF1-proficient cells under basal and curcumin-treated conditions, defining a distinct NF1-associated antioxidant-response context. Consistent with a functionally relevant redox-sensitive component, N-acetylcysteine pretreatment reduced curcumin-induced vacuolization to near-basal levels and substantially improved clonogenic recovery after drug washout. NF1-proficient Schwann cells showed an attenuated vacuolizing response, whereas acute NF1 silencing in hTERT RPE-1 cells enhanced curcumin-induced vacuolization in an independent cellular background. Together, these findings identify an NAC-sensitive vacuolizing response associated with loss of cellular fitness as a previously underappreciated vulnerability of NF1-deficient cells and provide a disease-relevant framework for understanding curcumin responsiveness in NF1.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 20","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13703259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149263337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Motor Deficits in a Mouse Model of Frontotemporal Dementia: Cortical Tau Pathology and Reduced Nigrostriatal Dopaminergic Markers.","authors":"Maciej Zadrożny, Patrycja Zadrożna, Wiktor Niewiadomski, Gernot Riedel, Charles R Harrington, Claude M Wischik, Grazyna Niewiadomska, Anna Gasiorowska-Bien","doi":"10.3390/cells15201908","DOIUrl":"10.3390/cells15201908","url":null,"abstract":"<p><p>Mice carrying tauopathy-associated mutations are considered good models for frontotemporal dementia because they replicate key features of the human disease. In carriers of the P301S tau mutation, these include degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc), reduced striatal dopamine levels, and motor deficits. Such parkinsonian symptoms have been reproduced in mouse models and are accompanied by weakened glutamatergic transmission from the motor and premotor cortex to the striatum. Here, we examined transgenic female homozygous (L66-Homo) and female heterozygous (L66-Het) Line 66 mice, which express the full-length human tau protein carrying the P301S and G335D mutations and NMRI mice as controls. Our focus was on the movement anomalies recorded using the RotaRod and Traction tests, together with histological markers of tauopathy, dopaminergic and glutamatergic systems and possible neurological markers in the motor cortex, striatum and SNpc. Compared to wild-type controls, 9-month-old L66-Homo mice presented with distinct motor impairments in both tests, which were not seen in aged matched L66-Het mice. Compared to L66-Het mice, L66-Homo mice exhibited: (1) more pronounced impairment of the dopaminergic phenotype in SNpc neurons; (2) exacerbated loss of tyrosine hydroxylase staining in striatum; (3) weaker vesicular monoamine transporter 2 staining in SNpc, striatum and frontal cortex; (4) stronger anti-tau staining in striatum and frontal cortex; (5) similar degree of degeneration in frontal cortex; and (6) similar decline in glutaminase staining in striatum and frontal cortex. Surprisingly, no tau-enriched labelling was present in SNpc in both L66-Homo and L66-Het. Therefore, motor impairments in female L66-Homo mice are associated with tau pathology in the striatum and motor cortex, together with a loss of the dopaminergic markers in the SNpc despite an absence of detectable tau immunoreactivity. Altered functional interactions between the striatum and SNpc may contribute to the observed dopamine loss and motor impairment in this mouse model. As only female mice were studied, the applicability of these findings to males remains to be established.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 20","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13702886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149263433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Forskolin-Induced Lipid-Droplet Remodeling Is Associated with Improved Redox Homeostasis and Cryotolerance of Vitrified Porcine Oocytes and Parthenogenetic Embryos.","authors":"Jiehuan Xu, Yongliang Chen, Shaoli Cai, Jun Gao, Mengqian He, Caifeng Wu, Jianjun Dai, Shushan Zhang, Yi Bian, Lingwei Sun","doi":"10.3390/cells15201909","DOIUrl":"10.3390/cells15201909","url":null,"abstract":"<p><p>Cryopreservation of mammalian oocytes and embryos is essential for the long-term conservation of livestock germplasm resources. Porcine oocytes and embryos accumulate high levels of intracellular lipids. This heavy lipid load aggravates vitrification-related oxidative stress and mitochondrial redox disturbance, greatly reducing cellular cryotolerance and hindering reliable preservation of indigenous pig germplasm. This study aimed to develop a non-invasive metabolic intervention strategy to mitigate lipid-associated oxidative cryodamage and improve the post-thaw quality of porcine oocytes and parthenogenetic embryos. Porcine cumulus-oocyte complexes were treated with forskolin, an adenylate cyclase activator, throughout in vitro maturation. For embryo assays, parthenogenetic embryos received continuous forskolin supplementation during oocyte maturation and were vitrified at Day 2 (cleavage stage). Vitrification disrupted lipid-droplet structural integrity and perturbed multiple metabolic pathways. Enrichment of starch, sucrose and galactose metabolism should be interpreted with caution as computational outputs, alongside changes in glycine, serine and threonine metabolism. Cryoinjury further induced mitochondrial depolarization, excessive reactive oxygen species production, redox imbalance and early apoptosis, ultimately impairing cell viability and embryonic developmental competence. Continuous forskolin exposure during oocyte in vitro maturation (with matching treatment for embryo groups) triggered lipid-droplet remodeling. This remodeling was associated with restored mitochondrial redox homeostasis and suppressed oxidative stress and apoptosis in warmed oocytes and embryos. Forskolin treatment enhanced post-thaw survival and cleavage rates of vitrified oocytes, as well as survival of cryopreserved embryos. By contrast, blastocyst formation rate showed only a numerical, non-significant increase. In conclusion, non-invasive forskolin-driven lipid-droplet remodeling can mitigate vitrification-triggered oxidative damage to lipid droplets and mitochondria. This work provides a practical pre-cryopreservation optimization strategy based on redox protection. It supports improved oocyte experimental protocols and offers useful references for germplasm conservation of rare and endangered pig breeds.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 20","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13702999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149263443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}