Tissue & cell最新文献

{"title":"Pyroptosis-inducing nanomedicines: A dual-mode therapeutic framework for apoptosis-resistant lung cancer","authors":"Qamar Abuhassan ,&nbsp;Ghaleb Oriquat ,&nbsp;R. Roopashree ,&nbsp;Priya Priyadarshini Nayak ,&nbsp;T. Sudhakar ,&nbsp;Vipasha Sharma ,&nbsp;Ashish Singh Chauhan ,&nbsp;Mansur Aliev","doi":"10.1016/j.tice.2026.103361","DOIUrl":"10.1016/j.tice.2026.103361","url":null,"abstract":"<div><div>Overcoming therapeutic resistance remains one of the most critical challenges in the clinical management of non–small cell lung cancer (NSCLC). Most systemic therapies for advanced NSCLC rely on intact apoptotic execution, which inherently limits their durability once apoptotic competence is lost. In many advanced tumors, apoptosis is disrupted by TP53 dysfunction, persistent activation of anti-apoptotic survival programs, or epigenetic repression of death-executing genes, allowing malignant cells to persist under sustained therapeutic pressure. In this context, pyroptosis has emerged as an alternative regulated cell-death program that operates independently of classical apoptotic machinery. Unlike apoptosis, pyroptosis is driven by gasdermin-mediated membrane permeabilization and the release of pro-inflammatory mediators capable of reshaping local immune responses, making it particularly attractive for apoptosis-resistant tumors. This review examines recent advances in pyroptosis-inducing nanomedicines for apoptosis-resistant NSCLC, with a specific focus on delivery-relevant mechanisms, gasdermin activation nodes, immune remodeling effects, and key barriers to clinical translation. We discuss how tumor-responsive nanocarriers can be engineered to deliver inflammasome activators, redox-sensitive agents, epigenetic modulators, or caspase triggers selectively to malignant tissue, thereby minimizing off-target inflammation. Through controlled engagement of the caspase-1/GSDMD or caspase-3/GSDME axes, these systems induce localized membrane disruption, cytokine release, and enhanced antigen presentation in preclinical models. In selected settings, nano-enabled pyroptosis promotes immune cell infiltration and restores responsiveness to PD-1/PD-L1–based immunotherapy, particularly when combined with chemotherapy or radiotherapy. Despite these advances, clinical translation remains constrained by tumor heterogeneity, delivery inefficiency, and the need for stringent control of inflammatory spillover in lung tissue.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"100 ","pages":"Article 103361"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146143483","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":"Brexpiprazole induces acute cardiotoxicity via disrupting calcineurin/NFAT and calcium signaling pathway: A validation from biochemical, echocardiographic, histological, and computational analysis","authors":"Mohammed Alissa ,&nbsp;Suad A. Alghamdi ,&nbsp;Abdulkarim S. Binshaya ,&nbsp;Tawfiq N. Juraybi ,&nbsp;Awaji Y. Safhi ,&nbsp;Amal A. Albati ,&nbsp;Adil Abalkhail ,&nbsp;Adel M. Alqarni","doi":"10.1016/j.tice.2026.103340","DOIUrl":"10.1016/j.tice.2026.103340","url":null,"abstract":"<div><div>Brexpiprazole (BPZ) is a third-generation atypical antipsychotic drug that is reported to induce various organ toxicity in non-target organisms. The current investigation was conducted to explore the dose-dependent toxicity of BPZ on cardiac tissues. Thirty-six rats were divided into four groups including control, BPZ (3 mg/kg), BPZ (10 mg/kg), and BPZ (30 mg/kg) treated group. BPZ intoxication compromised mRNA expressions of Calcineurin/NFAT and Calcium Signaling Pathway as evidenced by increased expression of protein phosphatase 3 catalytic subunit alpha (PPP3CA), nuclear factor of activated T cells, cytoplasmic 3 (NFATC3), regulator of calcineurin 1 (RCAN1), and phospholamban (PLN) while downregulating the expression of Ryanodine receptor 2 (RYR2), calcium voltage-gated channel subunit alpha c (CACNA1C), ATPase sarcoplasmic/endoplasmic reticulum Ca^2 + transporting 2 (SERCA2). Oxidative stress was clearly observed given the level of reactive oxygen species (ROS) and malondialdehyde (MDA) was markedly elevated coupled with significant inhibition of endogenous antioxidant enzymes including, heme oxygenase-1 (HO-1), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GSR), reduced glutathione (GSH) and glutathione S-transferase (GST) after BPZ intoxication. Functional cardiac impairment was further corroborated by significant changes occurring in echocardiographic parameters of myocardial impairment and ventricular dysfunction following the exposure of BPZ. Consistently, BPZ administration provoked the levels of creatine phosphokinase (CPK), B-type natriuretic peptide (BNP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), lactate dehydrogenase (LDH), creatine kinase-myocardial band (CK-MB), cardiac troponin I (cTnI) and cardiac troponin T (cTnT). Higher BPZ doses (10 and 30 mg/kg) triggered apoptotic imbalance, i.e., an increase in Cysteine-aspartic acid protease-3 (Caspase-3), Cysteine-aspartic acid protease-9 (Caspase-9), Bcl-2–associated X protein (Bax), while a significant reduction in the levels of B cell lymphoma-2 (Bcl-2). Histopathological evaluation showed severe myocardial damage in cardiac morphology following the intoxication of BPZ. In silico analyses supported these results showing binding affinity of BPZ with important key regulatory proteins. Collectively, the obtained data suggest that long-term exposure to BPZ results in cardiotoxicity mediated by oxidative stress, inflammation, apoptosis, and functional cardiac dysfunction.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"100 ","pages":"Article 103340"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146039546","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":"A promising strategy to rapidly expand high-quality human limbal stem cells for tissue engineering and cornea reconstruction","authors":"Keng-Liang Ou ,&nbsp;Hsieh-Tsung Shen ,&nbsp;Chi-Hsun Tsai ,&nbsp;Takashi Saito ,&nbsp;Chia-Yu Wu","doi":"10.1016/j.tice.2026.103343","DOIUrl":"10.1016/j.tice.2026.103343","url":null,"abstract":"<div><div>The present study investigated a promising strategy for scaling up the expansion of high-quality human limbal stem cells (LSCs) <em>in vitro</em>. The LSCs isolated from human cornea biopsies were cultured with Mitomycin-C (MMC)-treated Swiss-3T3 feeder layers using three different methods: LSCs with MMC-treated Swiss-3T3 (L with MS), LSCs on MMC-treated Swiss-3T3 (L on MS), and LSCs on reverse MMC-treated Swiss-3T3 (L on RMS). Cell morphology, purity, and differentiation during culture were examined through light microscopy, flow cytometry, immunofluorescence staining, and reverse transcription-polymerase chain reaction (RT-PCR). Results showed that the LSCs continued to grow and exhibited the highest expression of p63 + cells (99.5 ± 0.5 %) in the L on RMS method. After 7 days of culture, the L on RMS method exhibited a significantly higher cell expansion rate than the L with MS method (**<em>p</em> &lt; 0.01). Moreover, RT-PCR demonstrated that the cultured LSCs could naturally differentiate into epithelial cells, indicated by K3 expression. The cells could also efficiently form colonies while maintaining their stem cell markers. Therefore, the L on RMS method is promising for rapidly expanding high-quality LSCs and preserving their growth and stemness for corneal tissue engineering and reconstructive surgery.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"100 ","pages":"Article 103343"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146039616","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":"A synergistic protective network of Polygonatum sibiricum-derived carbon nanoparticles against ethanol-induced and oxidative hepatic injury in HepG2 cells","authors":"Hongjun Jiang ,&nbsp;Jiaxin Li ,&nbsp;Qinxun Zhu ,&nbsp;Xiongwei Liu ,&nbsp;Xin Wei ,&nbsp;Zuhua Wang ,&nbsp;Ying Zhou ,&nbsp;Tingting Feng","doi":"10.1016/j.tice.2026.103380","DOIUrl":"10.1016/j.tice.2026.103380","url":null,"abstract":"<div><div>Liver disease remains a major global health burden. This study investigated the protective effects of <em>Polygonatum sibiricum</em>–derived carbon nanoparticles (PS-CNPs) against ethanol-induced and oxidative stress-mediated injury in HepG2 cells. The obtained PS-CNPs exhibited a uniform near-spherical morphology, amorphous carbon structure, and notable photoluminescence. PS-CNPs showed significant free radical-scavenging capacity against DPPH and reduced hydrogen peroxide (H₂O₂)-induced reactive oxygen species (ROS) generation in L929 cells in a concentration-dependent manner. Cytotoxicity assays indicated that PS-CNPs had low toxicity. Mechanistic studies revealed that PS-CNPs exerted hepatoprotective effects through a multi-level synergistic mechanism. The core of this mechanism contributed to the restoration of mitochondrial function by recovering Complex I activity, reducing ROS burst, and stabilizing the mitochondrial membrane potential. Consequently, PS-CNPs maintained cellular energy homeostasis and inhibited apoptosis. Furthermore, in alcoholic injury, PS-CNPs promoted ethanol metabolism (enhanced ADH activity) and maintained energy balance (restored LDH activity). In both injury models, they potently activated the endogenous antioxidant defense system (increased SOD and CAT activities, decreased MDA levels). These effects collectively formed a synergistic network extending from mitochondrial protection to overall cellular functional improvement, significantly reversing the decline in cell viability. In conclusion, this study demonstrated that PS-CNPs were a promising nanomaterial with multi-target protective potential. Their mechanism, centered on mitochondrial repair, synergistically enhanced detoxification, metabolic, and antioxidant functions, thereby providing a crucial theoretical foundation for the development of novel hepatoprotective agents.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"100 ","pages":"Article 103380"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146182485","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":"Protective effects of linagliptin and tenofovir disoproxil fumarate against APAP-induced acute liver injury: A biochemical, histological, and computational study","authors":"Mahnoor Yamin ,&nbsp;Muhammad Ali ,&nbsp;Arifa Mehreen ,&nbsp;Bushra Akhtar ,&nbsp;Mansour Abdulaziz Alsaleem ,&nbsp;Salim Jamil ,&nbsp;Ahmed Al-Emam ,&nbsp;Hesham M. Hassan","doi":"10.1016/j.tice.2026.103374","DOIUrl":"10.1016/j.tice.2026.103374","url":null,"abstract":"<div><div>Hepatic injuries are one of the leading threats to public health which can further lead to liver diseases such as liver fibrosis and cirrhosis. An overdose of certain chemicals and drugs can cause hepatotoxicity, which leads to drug-induced liver injury. Linagliptin is an effective drug in treating type 2 diabetes, as it has been shown to reduce oxidative stress. Tenofovir (an antiretroviral) is the first-line treatment for hepatitis B and AIDS; it inhibited the production of reactive oxygen species (ROS) and reduced inflammation. The present research was conducted to assess protective effect of two FDA-approved repurposed (anti-diabetic and antiretroviral) drugs against APAP-induced acute liver injury in mouse models. A multi-model approach was applied by integrating <em>in vivo</em>, <em>in vitro, and silico</em> techniques with histopathological analysis. APAP injection enhanced ALT, AST, ALP, and bilirubin levels. In vivo analysis exhibited ameliorated liver injury with Lina and TDF, as evidenced by significantly lowered liver injury markers. Combination therapy normalized insulin levels, indicating improved glycemic control. Both drugs increased TAC and decreased levels of TOS and MDA. In Silico studies revealed a strong interaction between Lina and TDF with pro-inflammatory receptors, including JNK, TNF-α, and IL-1. Histopathological analysis further proved the reversal of acute liver injury. Together, Lina and TDF acted as multi-target anti-liver injury drugs, indicating their potential as a promising hepato-therapeutic repurposed drug.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"100 ","pages":"Article 103374"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146182430","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":"Iron-quercetin complex ameliorates chronic kidney disease via inhibiting the renal TGF-β1/Smad3/Egr1 axis-mediated kidney injury and fibrosis","authors":"Jianchun Li ,&nbsp;Luna Zhang ,&nbsp;Qianqian Li ,&nbsp;Yuanxia Zou ,&nbsp;Yufang Ni ,&nbsp;Jiraporn Kantapan ,&nbsp;Nathupakorn Dechsupa ,&nbsp;Li Wang","doi":"10.1016/j.tice.2026.103349","DOIUrl":"10.1016/j.tice.2026.103349","url":null,"abstract":"<div><h3>Background</h3><div>Chronic kidney disease (CKD) remains a significant global health burden due to the lack of effective interventions. Here, we evaluated whether the metal-flavonoid compound, Iron-Quercetin complex (IronQ) can ameliorate CKD and examine its effect on the TGF-β1/Smad3/Egr1 signaling cascade.</div></div><div><h3>Methods</h3><div>To assess the IronQ’s therapeutic efficacy in renal fibrosis, two well-recognized <em>in vivo</em> models were employed: the unilateral ureteral obstruction (UUO) model and the adenine (Ade)-elicited renal fibrosis systems. The efficacy of IronQ was assessed through comprehensive analyses of renal injury and histopathological changes. In addition, an in vitro system of TGF-β1-induced profibrotic response was developed using renal fibroblasts (NRK-49F) and renal tubular cells (TCMK1) to dissect the cellular signaling. Furthermore, to elucidate the potential mechanisms by which IronQ ameliorates renal fibrosis, a proteomic screen was conducted to delineate the changes in protein expression after IronQ intervention.</div></div><div><h3>Results</h3><div>IronQ significantly improved biochemical parameters of kidney injury, evidenced by a marked decrease in serum creatinine and blood urea nitrogen (BUN) levels. Consistently, IronQ treatment attenuated renal fibrosis, which was evidenced by a decreased expression of extracellular matrix (ECM) markers, including α-SMA, FN, and Col1a1, as evidenced by immunohistochemistry, Western blot, and qRT-PCR analyses. In agreement with the <em>in vivo</em> findings, IronQ intervention also significantly reduced the fibrotic response in both NRK-49F and TCMK-1 cell lines. Proteomic analysis further demonstrated that IronQ specifically downregulated the TGF-β1-stimulated upregulation of Egr1. Subsequent validation confirmed that the IronQ intervention significantly suppressed Egr1 expression and inhibited the phosphorylation of Smad3. Importantly, co-immunoprecipitation results revealed that IronQ intervention directly inhibited the physical interaction between Egr1 and Smad3.</div></div><div><h3>Conclusion</h3><div>Our research demonstrates that IronQ is a promising therapeutic candidate for CKD, offering a novel strategy to combat renal fibrosis via targeting the TGF-β1/Smad3/Egr1 cascade.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"100 ","pages":"Article 103349"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146067268","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":"In vivo biocompatibility of poly-N-isopropylacrylamide (PNIPAM) hydrogels in Wistar rats: Hematological, biochemical, and histopathological assessments","authors":"Rocío Bonino ,&nbsp;Andrés Sommaro ,&nbsp;Virginia Capella ,&nbsp;Matías Caverzan ,&nbsp;Bianca Opizzo ,&nbsp;Lázaro Zabaldano ,&nbsp;Nancy Rodriguez ,&nbsp;Pablo Bosch ,&nbsp;Claudia Rivarola ,&nbsp;Ana Cecilia Liaudat","doi":"10.1016/j.tice.2026.103377","DOIUrl":"10.1016/j.tice.2026.103377","url":null,"abstract":"<div><div><em>In vitro</em> regeneration of different tissues requires the synthesis of a scaffold material and the compatibility with the desired cell type to achieve a functional unit for transplantation. Poly-<em>N</em>-isopropylacrylamide (PNIPAM) and cationic copolymers hydrogels are effective scaffolds, supporting cell <em>in vitro</em> adhesion and development without cytotoxicity. This study aimed to analyze the <em>in vivo</em> biocompatibility of PNIPAM and PNIPAM co-3 % APTA (3-((acrylamidopropyl) trimethyl-ammonium chloride, APTA)) 3D architecture implanted in female and male Wistar rats. Hydrogel half-discs were implanted in subcutaneous pockets of 3 rats per treatment group (control (without hydrogel), PNIPAM, and PNIPAM co-3 % APTA) for 30 days. The healing process was monitored and after 30 days, the rats were sacrificed following an approved animal care protocol. Blood samples were collected for hematological and biochemical analyses and hydrogels, kidneys, liver, and spleen samples for histopathological evaluation. The results showed no alterations in the healing process in all the animals evaluated. Hematological parameters, liver enzyme activities, nitrogenous waste products and histopathological studies showed no changes across all experimental groups. PNIPAM and PNIPAM co-3 % APTA hydrogels are biocompatible in a female and male murine model over a 30-day period, maintaining stable hematological, biochemical, and histological parameters without alterations.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"100 ","pages":"Article 103377"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146158263","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":"Integrative multi-omics profiling implicates purine metabolism and the PI3K-Akt pathway in radiation-induced lung injury","authors":"Jun Qiu ,&nbsp;Xinpan Li ,&nbsp;Yi Fang ,&nbsp;Qiaoyuan Wu ,&nbsp;Shixiong Liang","doi":"10.1016/j.tice.2026.103330","DOIUrl":"10.1016/j.tice.2026.103330","url":null,"abstract":"<div><h3>Background</h3><div>Thoracic radiotherapy commonly causes radiation-induced lung injury (RILI); however, its mechanisms remain poorly defined, and no FDA-approved therapies are available.</div></div><div><h3>Methods</h3><div>To identify key pathways and regulators, we analyzed metabolic and transcriptomic alterations in a murine model of RILI. Following a 15 Gy thoracic irradiation, lung tissues were assessed by histopathology (H&amp;E and Masson staining), LC-MS-based metabolomics, and transcriptomics.</div></div><div><h3>Results</h3><div>Irradiated lungs showed erythrocyte exudation, inflammatory infiltration, fibrosis, and epithelial damage, whereas control tissues showed no pathological changes. Metabolomic profiling identified 186 differentially abundant metabolites, primarily enriched in purine and glycine/serine/threonine metabolism. Transcriptomics revealed 180 differentially expressed genes. Integrative analysis demonstrated that both metabolites and genes converged on the PI3K–Akt and phospholipase D signaling pathways, suggesting their potential as early RILI biomarkers. Analyses also revealed a consistent association between RILI and lung microbiota dysbiosis, pointing to novel mechanistic insights.</div></div><div><h3>Conclusions</h3><div>Our integrative multi-omics analysis reveals that RILI progression is characterized by dysregulated purine metabolism and transcriptomic changes that converge on the PI3K-Akt and phospholipase D signaling pathways. These pathway alterations were associated with lung microbiota dysbiosis, providing new avenues for early biomarker discovery and therapeutic intervention.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"100 ","pages":"Article 103330"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146039545","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 METTL14/YTHDF3 axis regulates EPSTI1-mediated osteogenic differentiation of human bone marrow mesenchymal stem cells","authors":"Changjun Zheng ,&nbsp;Lingzhi Ding ,&nbsp;Yan Xu ,&nbsp;Chi Yuan ,&nbsp;Bingjie Jiang ,&nbsp;Tingting Chen ,&nbsp;Yongjie Wang","doi":"10.1016/j.tice.2026.103386","DOIUrl":"10.1016/j.tice.2026.103386","url":null,"abstract":"<div><h3>Background</h3><div>Osteoporosis is a disease characterized by impaired bone microarchitecture and reduced bone mass. However, its molecular mechanisms are not fully understood.</div></div><div><h3>Methods</h3><div>Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot (WB) were used to detect the expression of messenger RNA (mRNA) and proteins. Flow cytometry was used to quantify cell surface markers. Cell transfection was used for gene knockdown and overexpression. Cell counting kit-8 (CCK-8) and 5-ethynyl-2’-deoxyuridine (EdU) were used to assess cell viability and proliferation. Alkaline phosphatase (ALP) staining and alizarin red S (ARS) staining were used to evaluate ALP activity and osteogenic differentiation. RNA modification variant database 2.0 (RMVar 2.0), RNA modification base database 3.0 (RMbase V3.0), and sequence-based RNA adenosine methylation site predictor (SRAMP) were used to predict RNA modifications. RNA-protein interaction (RPI) database was used to predict RNA-protein interactions. RNA immunoprecipitation (RIP) and methylated RNA immunoprecipitation (MeRIP) were used to detect RNA-protein binding and RNA chemical modifications. Actinomycin D (Act D) was used to study mRNA stability. The encyclopedia of RNA interactomes (ENCORI) was used to predict interactions among RNA molecules.</div></div><div><h3>Results</h3><div>Epithelial-stromal interaction 1 (EPSTI1) was highly expressed in osteoporosis. Knockdown of EPSTI1 promoted hBMSC viability, proliferation, and osteogenic differentiation, whereas its overexpression produced the opposite effects. Methyltransferase-like 14 (METTL14) and YTH N6-methyladenosine RNA binding protein 3 (YTHDF3) co-regulated the N6-methyladenosine (m⁶A) modification of EPSTI1. METTL14 overexpression enhanced hBMSC viability, proliferation, and osteogenic differentiation, but simultaneous overexpression of EPSTI1 partially offset these promoting effects.</div></div><div><h3>Conclusion</h3><div>METTL14 and YTHDF3 regulate EPSTI1 expression through its m⁶A modification, thereby modulating proliferation and osteogenic differentiation of hBMSCs.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"100 ","pages":"Article 103386"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146190128","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":"Late prenatal development of the olfactory and vomeronasal systems in a wild rodent: The fossorial water vole","authors":"Sara Ruiz-Rubio ,&nbsp;Irene Ortiz-Leal ,&nbsp;Mateo V. Torres ,&nbsp;Aitor Somoano ,&nbsp;Taekyun Shin ,&nbsp;Pablo Sanchez-Quinteiro","doi":"10.1016/j.tice.2026.103388","DOIUrl":"10.1016/j.tice.2026.103388","url":null,"abstract":"<div><div>Chemical communication is essential for mammalian survival from the earliest stages of life, yet most of what is known about the prenatal development of the olfactory and vomeronasal systems comes from laboratory rodents. Here we investigated the fetal development of the nasal chemosensory systems in the fossorial water vole (<em>Arvicola scherman</em>), a free-living arvicoline rodent with a subterranean lifestyle. We analyzed fetuses at embryonic days E17 and E21 (term) using classical histology, immunohistochemistry and lectin histochemistry. This approach enabled to assess structural maturation, neuronal differentiation, and the temporal dynamics of glycoconjugate expression in the vomeronasal organ (VNO), olfactory epithelium, and the main (MOB) and accessory olfactory bulbs (AOB). By E21, the MOB displayed a layered adult-like organization with well-defined glomeruli and interneuronal populations, whereas the AOB showed delayed morphological maturation but already exhibited selective molecular signatures in its superficial layers. Prenatally, the VNO underwent conspicuous structural differentiation, including stratification of the sensory epithelium, axonal fasciculation, and development of vomeronasal glands. Immunohistochemical analysis revealed early expression of G-protein subunits and calcium-binding proteins, indicating premature pathway specification and interneuronal circuit formation. Lectin labeling provided additional insights: SBA emerged as a selective marker of the vomeronasal pathway; UEA characterized early compartmentalization of vomeronasal projections and LEA showed a pan-chemosensory binding pattern. Together, these findings demonstrate that <em>Arvicola scherman</em> exhibits a remarkably accelerated prenatal maturation of its chemosensory systems compared with laboratory rodents. This early functional readiness emphasizes the importance of incorporating wild species into developmental neurobiology to refine our understanding of chemosensory evolution.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"100 ","pages":"Article 103388"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146189724","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}