Experimental and molecular pathology最新文献

{"title":"Mechanisms and strategies for reversing NK cell exhaustion in tumor immunotherapy","authors":"Lingtong Zhi ,&nbsp;Yuqing Wang ,&nbsp;Zixing Zhao ,&nbsp;Yabin Guo ,&nbsp;Kaiwen Wang ,&nbsp;Wenhui He ,&nbsp;Changjiang Guo ,&nbsp;Zhiyuan Niu ,&nbsp;Wuling Zhu ,&nbsp;Xuan Zhang","doi":"10.1016/j.yexmp.2026.105031","DOIUrl":"10.1016/j.yexmp.2026.105031","url":null,"abstract":"<div><div>Natural Killer (NK) cells play a crucial role in the body's innate immune system, distinguished by their ability to target a wide array of tumors through diverse killing strategies. Following the intense focus on T cells, NK cells have emerged as a key player in immunotherapy. Recent advancements in NK cell-based cancer treatments, including adoptive cell therapy, immune checkpoint inhibition, recombinant cytokine therapies, and nanomedicines, have demonstrated promising outcomes both in vitro and in vivo. As research into NK cell-based therapies intensifies, evidence is mounting that NK cells undergo phenotypic changes, acquiring characteristics of exhaustion. Key features comprise reduced proliferative capacity, diminished cytokine production, altered receptor expression, as well as compromised lymph node homing and Tumor Microenvironment (TME) persistence. NK cell exhaustion not only reduces NK cell efficacy and number in solid tumor therapies, but it also plays a crucial role in treatment resistance and tumor cell evasion. Understanding the mechanisms behind NK cell exhaustion and developing strategies to counteract it within the suppressive TME are of paramount importance. In this review, we delineate the maturation and development of NK cells, emphasize the phenotypic characteristics and underlying mechanisms of NK cell exhaustion, systematically review the methods to mitigate NK cell exhaustion, and thoroughly discuss the current limitations of NK cell immunotherapy. Ultimately, we aim to provide potential solutions and future directions for enhancing NK cell-based cancer treatments.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"145 ","pages":"Article 105031"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antioxidant and neuroprotective effects of ubiquinol diacetate: Insights from SH-SY5Y cell line and Caenorhabditis elegans models of Parkinson's disease","authors":"Matteo Micucci ,&nbsp;Michela Battistelli ,&nbsp;Sabrina Burattini ,&nbsp;Riham Osman ,&nbsp;Francesco Onesimo ,&nbsp;Michele Mari ,&nbsp;Michele Retini ,&nbsp;Ilaria Versari ,&nbsp;Barbara Pagliarani ,&nbsp;Andrea Tarozzi ,&nbsp;Giovanni Zappia ,&nbsp;Federico Gianfanti ,&nbsp;Letizia Pruccoli","doi":"10.1016/j.yexmp.2026.105023","DOIUrl":"10.1016/j.yexmp.2026.105023","url":null,"abstract":"<div><div>Parkinson's disease (PD) is a neurodegenerative disease characterized by the degeneration of dopaminergic neurons in the substantia nigra and the presence of misfolded α-synuclein in the brain. Mitochondrial dysfunction and oxidative stress are factors contributing to the death of these neurons. Coenzyme Q10 (CoQ10) serve as an antioxidant and cofactor for mitochondrial enzymes, and its deficiency can exacerbate neurodegenerative processes in PD. However, the clinical efficacy of CoQ10 is limited by its low bioavailability and instability. Ubiquinol diacetate (CoQ10 Ac), an esterified form of CoQ10, shows improved pharmacokinetic properties and potential as a prodrug, converting into the reduced antioxidant form of CoQ10 by esterases in the body. This study aimed to investigate the antioxidant and neuroprotective effects of CoQ10 Ac compared to CoQ10 in SH-SY5Y cell line and <em>Caenorhabditis elegans</em> models of PD. CoQ10 Ac showed higher antioxidant activity than CoQ10 at both extracellular and intracellular levels, particularly in the membrane and cytosolic compartments. It exhibited superior neuroprotection against 6-hydroxydopamine toxicity, showing a greater ability to reduce the activation of caspase-3 and PARP1 compared to CoQ10. Both compounds decreased the increased ratio of mitochondrial fission protein, DRP1, to fusion protein, OPA1, induced by 6-hydroxydopamine in SH-SY5Y cells, enhancing OPA1 levels and promoting antiapoptotic death. However, CoQ10 Ac was more effective than CoQ10 in preserving mitochondrial structural integrity and mass. Additionally, both compounds significantly inhibited the aggregation of α-synuclein induced by 6-hydroxydopamine. Furthermore, CoQ10 Ac showed stronger neuroprotective effects than CoQ10 in <em>C. elegans</em> models of PD. It demonstrated greater anti-aggregant activity in <em>C. elegans</em> expressing human α-synuclein, suggesting higher bioavailability. These findings highlight CoQ10 Ac as a promising prodrug candidate and support further investigation in <em>in vivo</em> PD models.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"145 ","pages":"Article 105023"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145972767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-21-5p dysregulation is associated with gut microbiota dysbiosis and pro-oncogenic markers in primary sclerosing cholangitis with concomitant inflammatory bowel disease","authors":"André Anastácio Santos ,&nbsp;David Pires ,&nbsp;Vanda Marques ,&nbsp;Nicole Alesina ,&nbsp;Pedro Miguel Rodrigues ,&nbsp;Ana Catarina Bravo ,&nbsp;Catarina Gouveia ,&nbsp;Susana Saraiva ,&nbsp;Luís Correia ,&nbsp;Ricardo Crespo ,&nbsp;João Pereira da Silva ,&nbsp;Marília Cravo ,&nbsp;Jesus Maria Banales ,&nbsp;Joana Torres ,&nbsp;Cecília Maria Pereira Rodrigues","doi":"10.1016/j.yexmp.2025.105013","DOIUrl":"10.1016/j.yexmp.2025.105013","url":null,"abstract":"<div><h3>Background</h3><div>Primary sclerosing cholangitis (PSC) is a chronic liver disease frequently associated with inflammatory bowel disease (IBD) and increased risk of colorectal cancer (CRC). Despite the strong association, the underlying mechanisms linking PSC-IBD, gut inflammation, and neoplastic potential remain unclear. This study explores the role of miR-21-5p dysregulation, gut microbiota dysbiosis, and pro-oncogenic markers in shaping the inflammatory and neoplastic microenvironment in PSC-IBD patients.</div></div><div><h3>Methods</h3><div>A case-control study was conducted, including PSC patients with concomitant IBD (<em>n</em> = 14) and control individuals without diagnosed PSC and IBD (<em>n</em> = 20). miR-21-5p levels were evaluated in serum, fecal samples, and colonic biopsies <em>via</em> qPCR. Gut microbiota composition was analyzed using 16S rRNA sequencing. Pro-oncogenic and inflammatory markers in colonic tissue were assessed <em>via</em> qPCR. <em>In vitro</em> studies were performed using cholangiocyte (H69), colorectal cancer (HCT116), and primary monocyte models to investigate the role of miR-21-5p.</div></div><div><h3>Results</h3><div>miR-21-5p was significantly upregulated in the right colon, serum, and fecal samples of PSC-IBD patients compared to controls. Gut microbiota analysis revealed dysbiosis, characterized by an increased <em>Bacteroidota</em>/<em>Bacillota</em> ratio and reduction in bile acid-metabolizing bacteria, including <em>Clostridium sensu stricto 1</em>, <em>Ruminococcaceae UCG-002</em>, and <em>Christensenellaceae_R7_group</em>. Colonic tissue analysis showed increased expression of EMT-related transcription factors <em>TWIST1</em> and <em>SNAIL</em>, inflammatory cytokines <em>IL-8</em>, <em>CCL2</em>, and <em>COX2</em>, and the stem cell marker <em>LGR5</em>. <em>In vitro</em> studies confirmed miR-21-5p role in upregulating <em>does</em> markers in monocytes and CRC cells.</div></div><div><h3>Conclusion</h3><div>This study found a link between miR-21-5p dysregulation and gut microbiota dysbiosis, colonic inflammation, and pro-oncogenic signaling in PSC-IBD patients. These findings highlight miR-21-5p as a potential modulator of disease progression and neoplastic risk.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"145 ","pages":"Article 105013"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145683827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the role of folate syntrophy and folate cross-feeding in the pathobiology of infectious-inflamed milieu caused by Fusobacterium nucleatum","authors":"Darab Ghadimi ,&nbsp;Sophia Blömer ,&nbsp;Aysel Şahin Kaya ,&nbsp;Sandra Krüger ,&nbsp;Christoph Röcken ,&nbsp;Heiner Schäfer ,&nbsp;Jumpei Uchiyama ,&nbsp;Shigenobu Matsuzaki ,&nbsp;Wilhelm Bockelmann","doi":"10.1016/j.yexmp.2025.105021","DOIUrl":"10.1016/j.yexmp.2025.105021","url":null,"abstract":"<div><div>Diet and nutrition affect almost every biological process, including multiple chronic diseases, diabetes, and some cancers. However, there are still significant gaps in our understanding of the importance of nutrition and healthy diets in syntrophy with respect to cross-feeding of the microbe-microbe and the microbe-host in the pathobiology of the infectious-inflamed intestinal milieu caused by anaerobic opportunistic bacteria such as <em>Fusobacterium nucleatum</em> (<em>F. nucleatum</em>). We examined the immune outcomes of three-member folate syntrophy and cross-feeding between <em>F. nucleatum</em> bacteria, endogenous folate-producing gut bacteria, and host cells at the host-pathogen interface using a triple co-culture model. T84, THP-1, and Huh7 cells were inoculated with <em>F. nucleatum</em> for 6 h in regular DMEM, DMEM with 9.5 μM folic acid, or with/without a mixture of <em>Bifidobacterium longum</em> subsp. <em>infantis</em> (<em>B. infantis</em>) and <em>Escherichia coli</em> Nissle <em>1917</em> (EcN). Cytokine secretion, cometabolite levels (ammonia, indoles), cell viability, and barrier integrity were assessed. <em>F. nucleatum-</em>induced folate depletion was associated with increased IL-1β and IL-6 and decreased IL-22, along with reduced transepithelial electrical resistance (TEER) and cell viability in T84 cells. Folate supplementation mitigated these effects. The mixture of <em>B. infantis</em> and EcN reduced <em>F. nucleatum</em>-induced pro-inflammatory cytokines, increased IL-22, and improved TEER and cell viability. These protective effects were enhanced by the addition of folate. <em>F. nucleatum</em> also elevated ammonia and reduced indoles, effects reversed by <em>B. infantis</em> and EcN. In addition to the intrinsic pathogenicity of harmful bacteria, folate deprivation, microbe–microbe folate syntrophy, and microbe–host folate cross-feeding contribute to the pathobiology of anaerobic opportunistic bacteria and influence the physiological fate of host cells. A combination of <em>B. infantis</em> and EcN modulates the infectious-inflamed interface through a cytoprotective effect and mechanical competitive extrusion of pathogenic <em>F. nucleatum</em>. These results provide potential insights into the mechanisms of early-onset colorectal cancer, and evidently, require future studies using patient-derived organoids and in vivo systems to improve clinical relevance.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"145 ","pages":"Article 105021"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal lung inflammation and apoptosis following gestational exposure to secondhand smoke and E-cigarette vapor: Implications for maternal-fetal health","authors":"Olivia Hiatt,&nbsp;Benjamin D. Davidson,&nbsp;Logan Beck,&nbsp;Katelyn A. Sturgis,&nbsp;Ethan Evans,&nbsp;Elizabeth Thurmond,&nbsp;Madeline Boyer,&nbsp;Benjamin T. Bikman,&nbsp;Paul R. Reynolds,&nbsp;Juan A. Arroyo","doi":"10.1016/j.yexmp.2026.105026","DOIUrl":"10.1016/j.yexmp.2026.105026","url":null,"abstract":"<div><div>Pregnancy is a vulnerable period where maternal exposure to environmental toxicants like secondhand smoke (SHS) and electronic cigarette (eCig) aerosols can harm maternal and fetal health. This study examines the differential impacts of SHS and eCig exposure on maternal lung tissue during late gestation, focusing on inflammation, apoptosis, and oxidative stress. Pregnant C57BL/6 mice were exposed to SHS or eCig aerosols for four or six days from embryonic day 12.5 or 14.5, with lung tissues collected on day 18.5 for analysis. Bronchoalveolar lavage fluid and lung tissue were assessed for inflammation, apoptosis, and oxidative stress. SHS exposure caused pronounced immune activation and mitochondrial-mediated apoptosis, while eCig exposure induced a milder inflammatory response with evidence of epithelial remodeling and oxidative imbalance. Collectively, both exposures disrupted maternal pulmonary homeostasis, with SHS producing stronger inflammatory effects. Unlike SHS, eCig exposure caused transient apoptosis with partial preservation of anti-apoptotic pathways (Bcl-2, IGF-1), while SHS exhibited stronger pro-inflammatory effects, eCig exposure still contributed to oxidative stress and immune dysregulation. These findings underscore the risks of both exposures during pregnancy, emphasizing the need for stringent public health policies regulating eCig use to protect maternal and fetal health.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"145 ","pages":"Article 105026"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding diabetes and its complications through the lens of Drosophila","authors":"Supriya Bevinakoppamath ,&nbsp;Anju Srinivas ,&nbsp;Chandan Gowda Umesha ,&nbsp;Akila Prashant ,&nbsp;Amanjot Singh ,&nbsp;Vinay Kumar Rao","doi":"10.1016/j.yexmp.2025.105017","DOIUrl":"10.1016/j.yexmp.2025.105017","url":null,"abstract":"<div><div>A significant gap exists between preclinical findings in animal models and their translation to diabetes therapeutics. Although several generic drugs are currently available, an effective and precise control of glycemia is challenging, and side effects due to both hyperglycemia and drugs are common. This is partly due to our incomplete understanding of disease mechanisms. It is now appreciated that, due to its simplicity and well-conserved genetic pathways, Drosophila disease modeling is an excellent choice for studying diabetes and its complications. Here, we review knowledge about conserved glucose sensing mechanisms, energy homeostasis pathways, and diabetes modeling in Drosophila. We discuss how hyperglycemia-induced metabolic deregulations cause diabetic complications. Further through the lens of Drosophila, we highlight molecular mechanisms underlying vascular and emerging diabetic complications, including neurodegeneration and cancer. We conclude with the thought that diabetes modeling in Drosophila could prove beneficial in large-scale screening of drugs for diabetes and its complications.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"145 ","pages":"Article 105017"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145767638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metixene hydrochloride hydrate mitigates kidney tubulointerstitial fibrosis by inhibiting Smad3 phosphorylation","authors":"Kyeong-Min Lee ,&nbsp;Yeo Jin Hwang","doi":"10.1016/j.yexmp.2026.105025","DOIUrl":"10.1016/j.yexmp.2026.105025","url":null,"abstract":"<div><div>Chronic Kidney disease (CKD), in which renal fibrosis is the defining pathological feature, poses significant global health and economic challenges. Despite its high clinical prevalence, effective therapies to prevent or reverse renal fibrosis remain scarce. Metixene hydrochloride hydrate (MHH), an anticholinergic drug once used for Parkinson's disease, has not been evaluated for renal fibrosis. Here, we investigated whether MHH mitigates renal fibrosis in a unilateral ureteral obstruction (UUO) mouse model and evaluated its effects on transforming growth factor-β1 (TGF-β1) signaling in renal cells. MHH did not affect the cell viability of NRK-49F cells at concentrations ranging from 0.5 to 5 μM. In vitro, MHH effectively suppressed TGF-β1-induced PAI-1 expression (both mRNA and protein) and secretion in renal fibroblasts, as well as PAI-1 secretion and protein expression in renal glomerular endothelial cells. Furthermore, TGF-β1 stimulated the mRNA and protein expressions of key renal fibrotic factors, including collagen type I, fibronectin, and alpha-smooth muscle actin, in NRK-49F cells. MMH significantly inhibited the expression of these renal fibrotic factors in these cells. UUO kidneys exhibited markedly increased tubular atrophy and interstitial fibrosis, as well as increased expression of renal fibrotic markers. MHH treatment significantly mitigated these pathological parameters and expression of renal fibrotic markers. Mechanistically, MHH suppressed TGF-β1-induced Smad3 phosphorylation both in vitro and in vivo. Our findings indicate that MHH exerts potent antifibrotic effects by downregulating the TGF-β1/Smad3 signaling pathway and suppressing the expression of fibrotic factors in renal cells and obstructed kidneys. Therefore, MHH could be repositioned as a therapeutic agent for renal fibrosis in various kidney diseases.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"145 ","pages":"Article 105025"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145972766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the characteristics of the SKP2-CDK6 axis in pancreatic cancer cell metastasis and its clinical significance","authors":"Hui-Ching Wang ,&nbsp;Chi-Wen Luo ,&nbsp;Sin-Hua Moi ,&nbsp;Ya-Hui Chang ,&nbsp;Shu-Jyuan Chang ,&nbsp;Yu-Hsuan Hung ,&nbsp;Tzu-Yi Chen ,&nbsp;Yi-Zi Chen ,&nbsp;Chiao-Ying Lai ,&nbsp;Yu-Ci Yang ,&nbsp;Chun-Chieh Wu ,&nbsp;Li-Tzong Chen ,&nbsp;Mei-Ren Pan","doi":"10.1016/j.yexmp.2026.105024","DOIUrl":"10.1016/j.yexmp.2026.105024","url":null,"abstract":"<div><h3>Background</h3><div>Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic malignancy with limited biomarkers for early detection. Recurrence and metastasis after surgical resection remain major causes of mortality, highlighting the urgent need for novel therapeutic strategies.</div></div><div><h3>Methods</h3><div>We integrated clinical database analyses and functional assays in PDAC cell lines and mouse models to investigate the role of the SKP2-CDK6 axis in tumor progression, metastasis, and gemcitabine resistance.</div></div><div><h3>Results</h3><div>Elevated CDK6 expression correlated with poorer progression-free and overall survival in PDAC patients and was associated with advanced stage and lymph node metastasis. SKP2 expression positively correlated with CDK6, and mechanistic studies revealed that SKP2 may transcriptionally regulate CDK6. Inhibition of CDK6 suppressed tumor growth and metastasis in vitro and in vivo, and reduced epithelial-mesenchymal transition. Combining a CDK6 inhibitor with gemcitabine significantly reduced colony formation in gemcitabine-resistant PDAC cells, suggesting a synergistic anticancer effect.</div></div><div><h3>Conclusions</h3><div>The SKP2-CDK6 axis may drive PDAC progression and chemoresistance. Co-targeting SKP2 and CDK6 in combination with gemcitabine may represent a promising therapeutic approach, warranting further preclinical and clinical evaluation to improve outcomes for patients with PDAC.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"145 ","pages":"Article 105024"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145972768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory role of protein tyrosine phosphatases in hematopoiesis and leukemogenesis","authors":"Xiaoting Wang ,&nbsp;Yuyao Guan ,&nbsp;Yizhuo Qin ,&nbsp;Zhen Guan ,&nbsp;guangsen Xu ,&nbsp;Yining Dong ,&nbsp;Zhiyuan Lu ,&nbsp;Xiuling Zhang ,&nbsp;Lei Zheng ,&nbsp;Qian Zhou","doi":"10.1016/j.yexmp.2026.105033","DOIUrl":"10.1016/j.yexmp.2026.105033","url":null,"abstract":"<div><div>Protein tyrosine phosphatases (PTPs), pivotal regulators of tyrosine phosphorylation dynamics, orchestrate cellular signaling networks to govern fundamental processes such as hematopoietic stem cell (HSC) quiescence, proliferation, and stress responses. Dysregulation of PTPs disrupts tyrosine phosphorylation homeostasis, culminating in HSC dysfunction, malignant transformation and leukemogenesis through aberrant activation of oncogenic pathways. This review summarizes the recent advances in understanding PTP-mediated mechanisms underlying HSC maintenance and leukemogenesis, with a focus on their dual roles as tumor suppressors and context-dependent oncogenic drivers. It could help explore the molecular mechanism of normal hematopoietic homeostasis and provide potential therapeutic targets of the related blood diseases.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"145 ","pages":"Article 105033"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147347922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of concern: “LncRNAs and miRNAs participate in determination of sensitivity of cancer cells to cisplatin” [Experimental and Molecular Pathology 123 (2021) 104602]","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"145 ","pages":"Article 105020"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147449064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}