MedScience最新文献_第3页

Targeting hemozoin detoxification in Plasmodium falciparum: could a chlorophyll derivative act as a tetrapyrrole mimic to disrupt hemozoin formation in infected erythrocytes? 针对恶性疟原虫的血色素解毒：叶绿素衍生物是否可以作为四吡咯模拟物来破坏感染红细胞中血色素的形成？

MedScience Pub Date : 2026-06-01 Epub Date: 2026-06-22 DOI: 10.1007/s11684-026-1214-2

Nicole Clark, Kirsten Heimann, Krasimir Vasilev, Richard Bright, Arduino A Mangoni

引用次数: 0

PDRG1 induced by SP1 facilitates the proliferation and metastasis of hepatocellular carcinoma by activating the Wnt/β-catenin pathway. SP1诱导的PDRG1通过激活Wnt/β-catenin通路促进肝细胞癌的增殖转移。

MedScience Pub Date : 2026-06-01 Epub Date: 2026-06-05 DOI: 10.1007/s11684-026-1237-8

Xudong Zhao, Shihua Lv, Haikuan Wang, Zeyi Lu, Pengcheng Kang, Jinglin Li, Liang Yu, Shihui Ma, Changxing Hua, Junqi You, Ziqiang Ge, Yi Xu, Yunfu Cui

{"title":"PDRG1 induced by SP1 facilitates the proliferation and metastasis of hepatocellular carcinoma by activating the Wnt/β-catenin pathway.","authors":"Xudong Zhao, Shihua Lv, Haikuan Wang, Zeyi Lu, Pengcheng Kang, Jinglin Li, Liang Yu, Shihui Ma, Changxing Hua, Junqi You, Ziqiang Ge, Yi Xu, Yunfu Cui","doi":"10.1007/s11684-026-1237-8","DOIUrl":"10.1007/s11684-026-1237-8","url":null,"abstract":"Hepatocellular carcinoma (HCC) remains a lethal malignancy with limited therapeutic targets. P53 and DNA damage-regulated gene 1 (PDRG1) has emerged as an oncogene in multiple cancers, yet its role and regulatory mechanism in HCC remain unclear. Here, we demonstrated that PDRG1 expression was significantly upregulated in HCC tissues compared to normal liver, correlating with advanced tumor stage, higher grade, and poor patient survival. Functionally, PDRG1 knockdown suppressed HCC cell proliferation, migration, and invasion in vitro and inhibited tumor growth and lung metastasis in vivo, whereas PDRG1 overexpression exerted opposite effects. Mechanistically, PDRG1 activated Wnt/β-catenin signaling, elevating levels of β-catenin, c-Myc, and phosphorylated GSK-3β, and the oncogenic effects of PDRG1 were reversed by the Wnt pathway inhibitor XAV939. Furthermore, transcription factor Specificity Protein 1 (SP1) bound directly to the PDRG1 promoter at the E3 site (-1927 to-1917) and activated its transcription. The pro-tumor effects of SP1 were rescued by PDRG1 silencing, indicating that SP1 acts through PDRG1. Collectively, our study identifies SP1 as an upstream transcriptional activator of PDRG1 and defines the SP1/PDRG1/Wnt/β-catenin axis as a key regulatory pathway promoting HCC progression, suggesting its potential as a prognostic biomarker and therapeutic target.","PeriodicalId":521275,"journal":{"name":"MedScience","volume":" ","pages":"496-514"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148166884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Innovative analysis and future prospects of Bupleuri Radix's pharmacology and toxicity based on the gut-liver axis. 基于肠肝轴的柴胡药理和毒性的创新分析及未来展望。

MedScience Pub Date : 2026-06-01 Epub Date: 2026-06-02 DOI: 10.1007/s11684-026-1213-3

Jie Ma, Qian Lu, Suoyan Tian, Zhiyuan Huang, Xinyu He, Xinyu Dai, Tongyan Jiao, Shenshen Yang, Yubo Li

{"title":"Innovative analysis and future prospects of Bupleuri Radix's pharmacology and toxicity based on the gut-liver axis.","authors":"Jie Ma, Qian Lu, Suoyan Tian, Zhiyuan Huang, Xinyu He, Xinyu Dai, Tongyan Jiao, Shenshen Yang, Yubo Li","doi":"10.1007/s11684-026-1213-3","DOIUrl":"10.1007/s11684-026-1213-3","url":null,"abstract":"Bupleuri Radix (BR) is a traditional Chinese medicine, which has a significant protective effect on hepatic and intestinal diseases, but its potential hepatotoxicity is still worrying. The bi-directional effects of BR are systematically summarized in this review, with a primary focus on the gut-liver axis. Saikosaponins, as the main bioactive components of BR, are converted by the gut microbiota into metabolites with enhanced bioavailability, thereby regulating the intestinal flora, strengthening the intestinal barrier, and alleviating inflammation through pathways such as NF-κB, PI3K/Akt/mTOR, and STAT3. Concurrently, BR and its components exert hepatoprotective effects through antioxidant, anti-inflammatory, and metabolic regulation mechanisms. However, saikosaponin and volatile oil may induce hepatotoxicity via oxidative stress and apoptosis. Critical evidence gaps persist regarding the systematic interplay between BR's multi-component actions and the gut-liver axis, the toxicity of metabolites, and clinical hepatotoxicity risk. Future research should prioritize these areas to optimize the safe and effective application of BR.","PeriodicalId":521275,"journal":{"name":"MedScience","volume":" ","pages":"418-443"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148146057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pathological complete response in a POLE-mutated non-small cell lung cancer patient treated with perioperative chemoimmunotherapy: a case report and review of the literature. 1例pole突变的非小细胞肺癌患者围手术期化疗免疫治疗的病理完全缓解：1例报告和文献复习。

MedScience Pub Date : 2026-06-01 Epub Date: 2026-07-01 DOI: 10.1007/s11684-026-1243-x

Luigi Liguori, Rosario De Feo, Lucia Santaniello, Brigida Miranda, Valentina Pagliara, Giovanna Polcaro, Alessandro Caputo, Giulia Cattaneo, Marco Ventin, Alberto Servetto, Cristina R Ferrone, Stefano Pepe, Francesco Sabbatino

{"title":"Pathological complete response in a POLE-mutated non-small cell lung cancer patient treated with perioperative chemoimmunotherapy: a case report and review of the literature.","authors":"Luigi Liguori, Rosario De Feo, Lucia Santaniello, Brigida Miranda, Valentina Pagliara, Giovanna Polcaro, Alessandro Caputo, Giulia Cattaneo, Marco Ventin, Alberto Servetto, Cristina R Ferrone, Stefano Pepe, Francesco Sabbatino","doi":"10.1007/s11684-026-1243-x","DOIUrl":"10.1007/s11684-026-1243-x","url":null,"abstract":"Immune checkpoint inhibitor (ICI)-based immunotherapy has emerged as an effective strategy for stage III non-small cell lung cancer (NSCLC). However, predictive biomarkers of response remain limited. DNA polymerase epsilon (POLE) mutations, although rare in NSCLC, are associated with an increased tumor mutational burden and enhanced neoantigen presentation, both of which may promote immune sensitivity. A 52-year-old woman was diagnosed with stage IIIA NSCLC. Tumor programmed death-ligand 1 (PD-L1) expression was negative. Molecular profiling revealed a somatic POLE mutation (NM_006231.4 (POLE): c.1270C>G (p.Leu424Val)), without additional tumor alterations. A perioperative chemo-immunotherapy approach was implemented. After three cycles of neoadjuvant carboplatin, pemetrexed, and pembrolizumab, computed tomography (CT) scan revealed a significant response. Then, the patient underwent to curative-intent surgery. Histopathological examination demonstrated a pathological complete response (pCR). Adjuvant pembrolizumab (thirteen cycles) was administered without relevant toxicities. At 18-month follow-up, the patient remained disease-free with good performance status. In conclusion, we report the case of pCR in a POLE-mutated NSCLC patient treated with perioperative chemo-immunotherapy. Incorporating a POLE evaluation could improve the integrated decision-making process for patients with NSCLC in the perioperative setting. Prospective studies are warranted to validate this observation.","PeriodicalId":521275,"journal":{"name":"MedScience","volume":" ","pages":"546-553"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148371768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Erratum to: Azvudine remodels the local immunosuppressive microenvironment and exhibits sustained anti-tumor effects in combination with anti-PD-1 therapies. 阿兹夫定重塑局部免疫抑制微环境，并与抗pd -1治疗联合表现出持续的抗肿瘤作用。

MedScience Pub Date : 2026-06-01 DOI: 10.1007/s11684-026-1251-x

Limin Jia, Zhaoyang Wang, Jinfa Du, Zhigang Ren, Jiandong Jiang, Pan Li

引用次数: 0

Loss of chromosome Y in hematopoietic cells: mechanisms and implications for human disease. 造血细胞中Y染色体缺失：机制及其对人类疾病的影响。

MedScience Pub Date : 2026-06-01 Epub Date: 2026-07-08 DOI: 10.1007/s11684-026-1246-7

Siyu Zhang, Zhen Zhang, Lan Wang, Meifang Qi

{"title":"Loss of chromosome Y in hematopoietic cells: mechanisms and implications for human disease.","authors":"Siyu Zhang, Zhen Zhang, Lan Wang, Meifang Qi","doi":"10.1007/s11684-026-1246-7","DOIUrl":"10.1007/s11684-026-1246-7","url":null,"abstract":"The chromosome Y, once thought to function primarily in male reproduction, is now recognized to have broader biological roles. Hematopoietic loss of chromosome Y (LOY) is one of the most frequent somatic genomic alterations in male blood, with prevalence increasing markedly with age. Advances in technology have enabled robust detection of LOY in blood at both the population scale and the single-cell level. Hematopoietic LOY arises from mitotic chromosome mis-segregation and is influenced by inherited genetic variation, environmental exposures, and aging. Population-based genome-wide association study (GWAS) analyses have identified robust epidemiological associations between hematopoietic LOY and cardiovascular disease, brain disease, immune disorders, and cancer. Mechanistic studies demonstrate that LOY has functional consequences, including altered gene expression, immune dysregulation, and clonal expansion. Some findings are strongly supported by CRISPR-based LOY mouse and cellular models, which recapitulate key disease-related phenotypes. Collectively, these findings establish hematopoietic LOY as a biologically meaningful form of somatic mosaicism with important implications for disease susceptibility.","PeriodicalId":521275,"journal":{"name":"MedScience","volume":" ","pages":"397-417"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148407928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TTP-like syndrome revealing advanced HIV infection: a case of secondary multifactorial thrombotic microangiopathy. ttp样综合征显示晚期HIV感染：继发性多因素血栓性微血管病1例。

MedScience Pub Date : 2026-06-01 Epub Date: 2026-07-01 DOI: 10.1007/s11684-026-1234-y

Alessandro Marrone, Martina Forestiero, Leopoldo Ricioppo, Elvira Stamile, Livia Bernardi, Francesca Sinopoli, Antonio Mastroianni, Francesca Greco, Nadia Caruso, Maria Raffaella Ambrosio, Tommaso Angelone, Rocco Malivindi, Cinzia Giordano, Stefania Catalano

{"title":"TTP-like syndrome revealing advanced HIV infection: a case of secondary multifactorial thrombotic microangiopathy.","authors":"Alessandro Marrone, Martina Forestiero, Leopoldo Ricioppo, Elvira Stamile, Livia Bernardi, Francesca Sinopoli, Antonio Mastroianni, Francesca Greco, Nadia Caruso, Maria Raffaella Ambrosio, Tommaso Angelone, Rocco Malivindi, Cinzia Giordano, Stefania Catalano","doi":"10.1007/s11684-026-1234-y","DOIUrl":"10.1007/s11684-026-1234-y","url":null,"abstract":"Thrombotic thrombocytopenic purpura (TTP) is a rare but life-threatening hematological emergency defined by severe ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13) deficiency. However, TTP-like syndromes without ADAMTS13 reduction can occur in systemic infections such as human immunodeficiency virus (HIV), posing significant diagnostic and therapeutic challenges, particularly in high-risk and underdiagnosed populations. We report the case of a 45-year-old transgender woman who presented to the emergency department with abdominal and lumbar pain, severe anemia, and thrombocytopenia. Laboratory tests revealed schistocytes, elevated lactate dehydrogenase (LDH), and indirect hyperbilirubinemia, prompting a high PLASMIC score and the initiation of plasma exchange for suspected TTP. Subsequent investigations revealed a preserved ADAMTS13 activity and uncovered a previously undiagnosed advanced HIV infection, along with Epstein-Barr virus (EBV) and human herpesvirus 8 (HHV-8) viremia. Despite timely initiation of antiretroviral therapy and comprehensive supportive care, the patient experienced progressive clinical deterioration and died during hospitalization. This case illustrates a multifactorial secondary thrombotic microangiopathy (TMA) mimicking primary TTP, triggered by advanced HIV and possibly exacerbated by estrogen-associated prothrombotic risk. It highlights the importance of early virologic screening and broad diagnostic reasoning in high-risk patients with overlapping prothrombotic conditions, where identifying the underlying cause of secondary TMA is critical to improving outcomes and preventing missed opportunities for life-saving intervention.","PeriodicalId":521275,"journal":{"name":"MedScience","volume":" ","pages":"532-538"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148371788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CRISPR screening reveals NPC1L1 as a key driver of glioblastoma progression via cholesterol metabolic regulation. CRISPR筛选显示NPC1L1通过胆固醇代谢调节是胶质母细胞瘤进展的关键驱动因素。

MedScience Pub Date : 2026-06-01 Epub Date: 2026-07-17 DOI: 10.1007/s11684-026-1228-9

Xiao Liu, Guangzhao Yang, Haozhe Qin, Qi Zhang, Zhihao Guan, Maorong Zhu, Cheng Zou, Yawen Wang, Yuxin Wu, Duo Yu, Dan Zheng, Juan Li, Jintao Gu, Zhengcong Cao, Zhengmin Li, Yalong He, Wei Lin

{"title":"CRISPR screening reveals NPC1L1 as a key driver of glioblastoma progression via cholesterol metabolic regulation.","authors":"Xiao Liu, Guangzhao Yang, Haozhe Qin, Qi Zhang, Zhihao Guan, Maorong Zhu, Cheng Zou, Yawen Wang, Yuxin Wu, Duo Yu, Dan Zheng, Juan Li, Jintao Gu, Zhengcong Cao, Zhengmin Li, Yalong He, Wei Lin","doi":"10.1007/s11684-026-1228-9","DOIUrl":"10.1007/s11684-026-1228-9","url":null,"abstract":"Glioblastoma (GBM), the most aggressive central nervous system (CNS) malignancy, currently lacks curative therapeutic options. While immunotherapy has revolutionized treatment for many cancers, GBM remains refractory to immune-based interventions due to the absence of effective immunotherapeutic targets. Here, through CRISPR screening, we identify Niemann-Pick C1-like 1 (NPC1L1) as a previously unrecognized key driver of GBM progression. Mechanistically, NPC1L1 modulates cholesterol metabolism to concurrently enhance tumor cell stemness and suppress CD8+ T-cell activation, thus inducing tumor progression. Notably, combined treatment with ezetimibe (NPC1L1 inhibitor) and anti-PD-1 antibody elicited potent antitumor activity in GBM orthotopic mouse models. Collectively, these findings establish NPC1L1 as a critical regulator of GBM pathogenesis, underscoring the translational potential of targeting NPC1L1-mediated cholesterol metabolism for developing novel GBM immunotherapies.","PeriodicalId":521275,"journal":{"name":"MedScience","volume":" ","pages":"473-482"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148475797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MedScience Pub Date : 2026-06-01 Epub Date: 2026-07-17 DOI: 10.1007/s11684-026-1221-3

Yue Liu, Hui Liang

{"title":"INPP5K-related muscular dystrophy caused by a novel synonymous splicing variant in a Chinese patient: a case report.","authors":"Yue Liu, Hui Liang","doi":"10.1007/s11684-026-1221-3","DOIUrl":"10.1007/s11684-026-1221-3","url":null,"abstract":"Congenital muscular dystrophies (CMDs) are a genetically heterogeneous group of disorders. Variants in the INPP5K gene, which encodes a phosphoinositide phosphatase, are a rare cause of CMD. The condition is commonly associated with muscle weakness, early-onset cataracts, and intellectual disability, and prior reports have primarily identified missense, frameshift, or deletion variants. We describe the first Chinese case of INPP5K-related muscular dystrophy in a 28-year-old male with a mild phenotype, notably lacking intellectual disability. His presentation included bilateral cataracts at age 5 and adolescent onset limb girdle weakness. Muscle magnetic resonance imaging (MRI) revealed a characteristic pattern of selective fatty infiltration, with severe involvement of gluteal and thigh muscles and striking sparing of the rectus femoris, sartorius, and gracilis. Genetic analysis identified compound heterozygous novel INPP5K variants: a missense c.274C>T, p.(Arg92Cys) and a synonymous c.261G>A, p.(Lys87=) change. Functional studies confirmed the synonymous variant causes aberrant splicing (exon 3 skipping), leading to a frameshift and premature termination p.(Leu52SerfsTer49). According to American College of Medical Genetics and Genomics guidelines, the c.274C>T and c.261G>A variants were classified as likely pathogenic and pathogenic, respectively. This first report of a Chinese patient with INPP5K-related muscular dystrophy broadens both the genetic and clinical spectrum of the disorder. We identify the first disease-causing synonymous variant (via aberrant splicing) and a novel hypomorphic missense variant p.(Arg92Cys), the combination of which explains the attenuated phenotype lacking intellectual disability. Our case highlights the critical role of RNA analysis in diagnosing non-canonical variants and confirms the universal diagnostic relevance of the characteristic muscle MRI pattern.","PeriodicalId":521275,"journal":{"name":"MedScience","volume":" ","pages":"554-559"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148475803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

International risk assessment of Nipah virus outbreak and medium-long-term prevention and control prospects in China. 尼帕病毒疫情国际风险评估及中国中长期防控前景。

MedScience Pub Date : 2026-06-01 Epub Date: 2026-07-17 DOI: 10.1007/s11684-026-1249-4

Limei Wang, Hong Jiang

引用次数: 0