Biomedicine & Pharmacotherapy最新文献

{"title":"Targeting KCNN4 channels modulates microglial activation and apoptosis in a PD-relevant inflammatory model","authors":"Hao-Yuan Hung ,&nbsp;I-Hsun Li ,&nbsp;Yung-Ni Lin ,&nbsp;Ting-Yin Yeh ,&nbsp;Ke-Xin Ng ,&nbsp;Tin-An Wang ,&nbsp;Kun‑Ting Hong ,&nbsp;Teng-Hui Wang ,&nbsp;Yi-Chieh Wu ,&nbsp;Jui-Hu Shih","doi":"10.1016/j.biopha.2025.118526","DOIUrl":"10.1016/j.biopha.2025.118526","url":null,"abstract":"<div><div>Parkinson’s disease (PD) is characterized by chronic neuroinflammation and progressive dopaminergic neurodegeneration, driven primarily by the activation of microglia and associated apoptotic pathways. The intermediate-conductance calcium-activated potassium channel KCNN4 has recently emerged as a potential therapeutic target, yet its role in chronic neurodegenerative conditions remains underexplored. In this study, we investigated whether pharmacological inhibition of KCNN4 using TRAM-34 can modulate both inflammatory and apoptotic responses in an LPS-induced mouse model of PD. Our <em>in vivo</em> findings demonstrate that TRAM-34 suppressed microglial activation, evidenced by reduced COX-2 and lower TLR4 relative to LPS, together with attenuated IL-1β; striatal Iba1 morphology at Day 86 also indicated mitigated activation. Furthermore, TRAM-34 treatment preserved dopaminergic neurons, as shown by increased tyrosine hydroxylase immunoreactivity, and mitigated apoptotic signaling by decreasing phosphorylated p53, cytochrome c release, and cleaved PARP-1 levels. Importantly, [¹ ⁸F]FE-PE2I PET at Day 30 showed partial restoration of striatal DAT, aligning with the Day-86 immunohistochemistry. In parallel, behavioral assessments using the rotarod test demonstrated that TRAM-34 significantly ameliorated LPS-induced motor deficits, further supporting its functional neuroprotective effects. <em>In vitro</em> studies further revealed that KCNN4 inhibition attenuates microglial overactivation and suppresses downstream inflammatory and pro-apoptotic signaling pathways. These dual effects suggest that TRAM-34 attenuates PD progression by simultaneously targeting neuroinflammation and apoptosis. This study underscores the therapeutic potential of KCNN4 channel inhibition in modulating microglial function and preventing neuronal loss in PD. By bridging molecular mechanisms with translational outcomes, our findings pave the way for KCNN4-targeted strategies to mitigate neurodegeneration and improve patient outcomes in PD.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"191 ","pages":"Article 118526"},"PeriodicalIF":7.5,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144996424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential of matrine and osthole against copper-promoted lung cancer cell malignancy","authors":"Yinlan Xu,&nbsp;Hejun Liu,&nbsp;Haonan Guo,&nbsp;Jinmei Zheng,&nbsp;Ling Tao,&nbsp;Weidong Wu","doi":"10.1016/j.biopha.2025.118504","DOIUrl":"10.1016/j.biopha.2025.118504","url":null,"abstract":"<div><div>Non-small cell lung cancer (NSCLC) is the major type of malignant tumor in the lungs. Emerging epidemiological evidence implicates environmental copper exposure as a potential risk modulator for NSCLC progression. This study investigated the effects of low-dose Copper (Cu) exposure on A549 cells and evaluated the therapeutic potential of two natural compounds, osthole and matrine. The results demonstrated that Cu exposure (5 μg/mL, 12 h) significantly promoted the migration, invasion and colony formation of A549 cells (<em>P</em> &lt; 0.05), accompanied by a reduction in cell apoptosis, a decrease in ROS levels and an increase in mitochondrial membrane potential. Meanwhile, osthole and matrine treatment could reverse these phenotypes and arrest the cell cycle of A549 in the G1 phase. Transmission electron microscopy results revealed that Cu exposure induced slightly swollen mitochondria and as well as the increase in the number of mitochondria, while osthole and matrine treatments resulted in severe degenerative changes in mitochondria. Both qPCR and Western blot examinations indicated that Cu exposure promoted the expression of PGC-1α but inhibited the expressions of STAT1, TNF-α and IL-2. Osthole treatment could down-regulate the expression of PGC-1α and up-regulate the expressions of STAT1, TNF-α and IL-2, while matrine treatments could up-regulate the expressions of STAT1 and TNF-α and down-regulate the expressions of PGC-1α and IL-2. Taken together, these findings indicate that low-dose Cu exposure can promote the proliferation, migration, invasion and mitochondrial damage of A549 cells, while osthole and matrine treatments inhibit Cu effects by regulating the STAT1, BGC-1 α, TNF-α and IL-2.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"191 ","pages":"Article 118504"},"PeriodicalIF":7.5,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145003705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Taurine suppresses Aβ aggregation and attenuates Alzheimer’s disease pathologies in 5XFAD mice and patient-derived cerebral organoids","authors":"Hyewon Lee ,&nbsp;Muhammad Kamal Hossain ,&nbsp;Hwa-Young Lee ,&nbsp;Vijay Kumar ,&nbsp;Soo Jung Shin ,&nbsp;Byeong-Hyeon Kim ,&nbsp;Hyun Ha Park ,&nbsp;Jeong Gyu Son ,&nbsp;Minho Moon ,&nbsp;Hyung-Ryong Kim","doi":"10.1016/j.biopha.2025.118527","DOIUrl":"10.1016/j.biopha.2025.118527","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is marked by amyloid-beta (Aβ) plaque buildup, tau hyperphosphorylation, neuroinflammation, neuronal loss, and impaired adult hippocampal neurogenesis (AHN). Taurine has shown protective effects in various cellular and animal models of AD, though the molecular mechanisms of free taurine and its effects in patient-derived models remain underexplored. This study evaluates taurine’s therapeutic potential using integrated <em>in silico</em>, <em>in vitro</em>, <em>in vivo</em>, and <em>ex vivo</em> approaches. <em>In vitro</em> aggregation assays revealed that taurine (10–100 μM) inhibited Aβ₄₂ fibril formation, with transmission electron microscopy showing looser, amorphous fibrils, particularly at higher doses. Computational simulations further supported that taurine binds stably to Aβ peptide fragments and facilitates the dissociation of Aβ dimers. In HT22 cells, taurine protected against Aβ-induced cytotoxicity. In 5XFAD mice, oral administration of taurine (1000 mg/kg, 4 weeks) significantly reduced Aβ accumulation and hyperphosphorylation of tau at Ser202/Thr205 in the dorsal subiculum. Furthermore, taurine attenuated microgliosis, as evidenced by decreased Iba-1 immunoreactivity, protected against neurodegeneration demonstrated by preserving NeuN-positive neurons, and ameliorated deficit of AHN shown by increasing DCX-positive cells in the subgranular zone of the dentate gyrus. Importantly, in cerebral organoids derived from an AD patient carrying the APOE ε4/ε4 genotype, taurine treatment attenuated Aβ accumulation, decreased tau phosphorylation. These findings highlight taurine’s multi-target therapeutic potential targeting amyloid aggregation, tau pathology, neuroinflammation and neurogenesis. Our data support taurine emerges as a promising therapeutic candidate for AD.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"191 ","pages":"Article 118527"},"PeriodicalIF":7.5,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144996422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coumarin attenuates cyclophosphamide-induced premature ovarian failure in mice by suppressing oxidative stress and apoptosis","authors":"Negar Pouladvand ,&nbsp;Mahnaz Azarnia ,&nbsp;Rouhollah Fathi ,&nbsp;Hadis Zeinali ,&nbsp;Samira Vesali ,&nbsp;Somayeh Tavana","doi":"10.1016/j.biopha.2025.118528","DOIUrl":"10.1016/j.biopha.2025.118528","url":null,"abstract":"<div><div>Cyclophosphamide (CTX) is a chemotherapy alkylating agent that causes many side effects, including the occurrence of Premature ovarian failure (POF). The present study aims to investigate the effects of coumarin (COU), as an antioxidant, on apoptosis and oxidative stress in the CTX-induced POF mouse model. NMRI female mice were randomly divided into four groups: 1- The control group received 200 mg/kg normal saline every two days for 6 days. 2- The POF group was administered three 200 mg/kg doses of CTX every two days. 3- The COU group received 40 mg/kg of coumarin for 14 days. 4- The POF+COU group received 40 mg/kg coumarin for 7 days before and after the induction of the POF mouse model. Vaginal smears, weighing, hormonal, histological, and biochemical factors, as well as the expression of apoptosis genes, were evaluated after inducing the POF model. Coumarin effectively reduced estrous cycle disorders, leading to a more regular cycling pattern. COU increased both ovarian and body weight, and improved hormone levels. Ovarian reserve and antral follicles in the POF+COU group increased significantly compared to the POF group. Compared to the POF group, the POF+COU group showed a significant decrease in ROS and a significant increase in antioxidant enzymes. COU-treated groups showed a significant reduction in the expression of <em>Caspase-8</em> and <em>Caspase-9</em> genes and the apoptosis index compared to the POF group. As a plant antioxidant, coumarin could improve ovarian function and reduce apoptosis and oxidative stress in the POF mouse model.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"191 ","pages":"Article 118528"},"PeriodicalIF":7.5,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144987949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lawsone can suppress liver fibrosis by inhibition of YAP signaling and induction of CYGB expression in hepatic stellate cells","authors":"Atsuko Daikoku ,&nbsp;Tsutomu Matsubara ,&nbsp;Misako Sato-Matsubara ,&nbsp;Miku Ando ,&nbsp;Chiho Kadono ,&nbsp;Sayuri Takada ,&nbsp;Naoshi Odagiri ,&nbsp;Hideto Yuasa ,&nbsp;Hayato Urushima ,&nbsp;Katsutoshi Yoshizato ,&nbsp;Norifumi Kawada ,&nbsp;Kazuo Ikeda","doi":"10.1016/j.biopha.2025.118520","DOIUrl":"10.1016/j.biopha.2025.118520","url":null,"abstract":"<div><div>Liver fibrosis, which eventually leads to cirrhosis, is characterized by excessive accumulation of type I collagen (COL1A), mainly derived from activated hepatic stellate cells (HSCs). Currently, there is no clinical treatments that can directly address this condition. The objectives of this study were to identify a compound that can suppress HSC activation and elucidate the molecular mechanism underlying its action. Chemical screening of antifibrogenic drugs was performed using a human COL1A2 promoter-based chemical screening system. Upon screening 1880 compounds, lapachol (a 1,4-naphtoquinone analog) was identified as an inhibitor of HSC activation. Among the tested 1,4-naphtoquinone analogs, we found that lawsone (LWS) robustly inhibited HSC activation by suppressing the expression of alpha-smooth muscle actin (αSMA) and enhancing the expression of cytoglobin (CYGB). LWS attenuated the assembly of actin filament and reduced the levels of Yes-associated protein (YAP) in HSCs with and without transforming growth factor-beta (TGFβ) exposure. Overexpression of YAP enhanced mRNA and protein levels of <em>COL1A</em> and <em>αSMA</em> in HSCs, but not of CYGB. These results strongly indicate that LWS suppresses HSC activation by decreasing YAP protein levels, suggesting that LWS induces CYGB expression independently of YAP. Furthermore, LWS alleviated thioacetamide- and 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced liver fibrosis by reducing YAP levels in the liver. This study provided evidence that LWS suppresses liver fibrosis by inhibiting YAP signaling and inducing CYGB expression.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"191 ","pages":"Article 118520"},"PeriodicalIF":7.5,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144996423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Scoping Review of Chemical, Pharmacological and Toxicological Properties and Clinical Applications of Australian Indigenous Medicine","authors":"Kayla Jaye ,&nbsp;Indeewarie Hemamali Dissanayake ,&nbsp;Deep Jyoti Bhuyan ,&nbsp;Dennis Chang","doi":"10.1016/j.biopha.2025.118503","DOIUrl":"10.1016/j.biopha.2025.118503","url":null,"abstract":"<div><div>Indigenous Australians have long recognised and utilised the therapeutic potential of Australian native plants for generations to treat and manage various diseases. In recent years, these native plants have been explored in preclinical research for their chemical profiles and therapeutic properties for conditions such as skin disorders, colds and flu, various cancers, neurological disorders, metabolic syndrome, and other inflammatory conditions. Notable species studied include Kakadu plum, Davidson’s plum, Burdekin plum, Illawarra plum, anise myrtle, lemon myrtle, lemon aspen, quandong, muntries, and Tasmanian pepperberry. Key bioactive compounds identified in these plants include polyphenols, ellagic acid, anthocyanins, flavonoids, and hydrolysable tannins. This review aims to compile and summarise the existing preclinical and clinical research investigating the chemical, pharmacological, and toxicological properties of Australian Indigenous Medicines. It also seeks to address the challenges and obstacles encountered in Australian Indigenous Medicine research and highlight innovative methodological approaches that can be employed in the future.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"191 ","pages":"Article 118503"},"PeriodicalIF":7.5,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144987924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenylketonuria: A guide through the complex maze of its neurological pathophysiology providing a new perspective on treatment strategies","authors":"Ine Nulmans,&nbsp;Sien Lequeue,&nbsp;Liesbeth Desmet,&nbsp;Gigly G. Del’haye,&nbsp;Nina S. Salvi,&nbsp;Matthias Rombaut,&nbsp;Jessie Neuckermans,&nbsp;Joery De Kock","doi":"10.1016/j.biopha.2025.118522","DOIUrl":"10.1016/j.biopha.2025.118522","url":null,"abstract":"<div><div>Phenylketonuria (PKU), an autosomal recessive disease caused by a deficiency in the phenylalanine-4-hydroxylase enzyme or its cofactor tetrahydrobiopterin, is characterized by excessive phenylalanine (Phe) and reduced tyrosine (Tyr) levels and typically manifests neurologically. Even early treated PKU patients with proper metabolic control, obtained immediately after birth upon diagnosis of the disease, show late-onset neurological complications. Although the disease has already been researched for over 90 years, the complexity of its neurological pathophysiology has only recently been unraveled. Where it was initially thought that the neurological phenotype could be attributed to the increased Phe and decreased Tyr levels resulting in impaired neurotransmitter synthesis, it is now hypothesized that other processes including alterations in protein synthesis, oxidative stress, changes in bioenergetics and white matter disturbances play an important role in the development of these neurological manifestations. In this review, we aim to guide you through the complex maze of the brain pathophysiology observed in PKU while providing a new perspective on future treatment strategies in order to completely overcome symptom onset.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"191 ","pages":"Article 118522"},"PeriodicalIF":7.5,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144987948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroavailable peptides from hempseed protein hydrolysates reduce hippocampal inflammation and glial activation in a scopolamine-induced Alzheimer’s disease","authors":"Maria Torrecillas-Lopez ,&nbsp;Carmen M. Claro-Cala ,&nbsp;Teresa Gonzalez-de la Rosa ,&nbsp;Luna Barrera-Chamorro ,&nbsp;M. Carmen Millan-Linares ,&nbsp;Elvira Marquez-Paradas ,&nbsp;Alvaro Villanueva ,&nbsp;Jose L. del Rio-Vazquez ,&nbsp;Sergio Montserrat-de la Paz","doi":"10.1016/j.biopha.2025.118438","DOIUrl":"10.1016/j.biopha.2025.118438","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive impairment, synaptic dysfunction, and neuronal loss. Neuroinflammation, driven by the activation of microglia and astrocytes, is a key contributor to AD pathology, amplifying oxidative stress and amyloid-β toxicity. Modulation of neuroinflammatory pathways thus represents a promising therapeutic strategy. In this study, we evaluated the effects of a food-grade hempseed protein hydrolysate (HPH20A) on hippocampal inflammation and glial activation in a scopolamine-induced mouse model of AD. Mice were orally supplemented with HPH20A (10 mg/kg/day) for 12 weeks. Hippocampal tissue was analyzed by RT-qPCR and immunohistochemistry to assess the expression of glial and inflammatory markers. To identify peptides capable of reaching the brain, we employed a double transwell <em>in vitro</em> system simulating intestinal and blood–brain barrier (BBB) transport, followed by LC-TIMS-MS/MS peptidomics, <em>in silico</em> bioactivity prediction, and molecular docking. HPH20A supplementation significantly attenuated the expression of pro-inflammatory markers, including GFAP, IBA1, TREM2, CD68, iNOS, COX2, and IL-6, and increased the anti-inflammatory cytokine IL-10. Peptidomic analysis identified two peptides, NVDTELAHKL and DSETVKRL, consistently present across intestinal, systemic, and brain compartments. These peptides were predicted to exhibit anti-inflammatory activity and demonstrated high-affinity binding to AD-related targets (APP, TREM2, and AChE) in docking simulations. Taken together, these findings suggest that HPH20A exerts neuroprotective effects by modulating hippocampal inflammation inflammation, potentially through specific bioactive peptides capable of crossing the BBB. Our results support the potential of hempseed-derived peptides as dietary modulators of neuroinflammation in early stages of neurodegenerative disease.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"191 ","pages":"Article 118438"},"PeriodicalIF":7.5,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144987972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autophagy in colorectal cancer: Current understanding of mechanisms and future therapeutic directions","authors":"Zhaoxia Qu ,&nbsp;Xinhui Pen ,&nbsp;Youbin Liu ,&nbsp;Xiaozhen Pen ,&nbsp;Xingjun Lu ,&nbsp;Shunli Luo","doi":"10.1016/j.biopha.2025.118524","DOIUrl":"10.1016/j.biopha.2025.118524","url":null,"abstract":"<div><div>Colorectal cancer (CRC) ranks among the most prevalent malignancies globally, distinguished by its high incidence, significant mortality, and poor prognosis. Despite advancements in early screening and therapeutic strategies, clinical outcomes remain suboptimal. In recent years, autophagy has emerged as a pivotal focus in CRC research. Although numerous studies have explored the potential roles of autophagy in CRC, a comprehensive review of recent advances—especially regarding novel autophagy-targeting agents and their underlying mechanisms—remains limited. This review synthesizes recent literature elucidating the role of autophagy in CRC initiation and progression, with a focus on its diagnostic, therapeutic, and prognostic implications. In addition, we highlighted the ongoing controversies surrounding autophagy in CRC research, examined its dual-edged role in therapeutic contexts, and provided an in-depth discussion on leveraging autophagy modulators to block CRC progression. We critically examine current autophagy-based treatment modalities, highlight ongoing controversies, and outline future directions, including personalized autophagy modulation, the development of next-generation autophagy regulators, and cross-disciplinary research opportunities in CRC.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"191 ","pages":"Article 118524"},"PeriodicalIF":7.5,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144988115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Viral oncogenesis and immune remodeling: Decoding the therapeutic potential of immune checkpoint inhibitors in virus-associated cancers","authors":"Lihua Qi ,&nbsp;Bai Hu ,&nbsp;Canhui Cao ,&nbsp;Ting Peng ,&nbsp;Miaochun Xu ,&nbsp;Shiyi Liu ,&nbsp;Yashi Xu ,&nbsp;Xiaojie Liu ,&nbsp;Wencheng Ding ,&nbsp;Li Li ,&nbsp;Shitong Lin","doi":"10.1016/j.biopha.2025.118515","DOIUrl":"10.1016/j.biopha.2025.118515","url":null,"abstract":"<div><div>Various viruses are widely recognized as key contributors to the development of numerous hematological malignancies and solid tumors. It is estimated that virus-associated cancers account for approximately 1.5 million new cases globally each year. The major oncogenic viruses include Epstein-Barr virus (EBV), Kaposi’s sarcoma-associated herpesvirus (KSHV), hepatitis B and C viruses (HBV and HCV), human papillomavirus (HPV), human T-cell lymphotropic virus type 1 (HTLV-1), and Merkel cell polyomavirus (MCPyV). Notably, human immunodeficiency virus (HIV), though non-oncogenic itself, exacerbates malignancy risk through profound immunosuppression. Virus-associated tumors frequently exhibit intricate immune evasion mechanisms, influencing both disease progression and therapeutic outcomes. Immune checkpoint inhibitors (ICIs) have demonstrated clinical promise in this context. However, monotherapy remains constrained by suboptimal efficacy and acquired resistance. Emerging evidence highlights the synergistic potential of combining ICIs with both virus-directed immunotherapies, including therapeutic vaccines, TCR-T/CAR-T cells, and oncolytic viruses, and other targeted or anti-angiogenic agents to reverse T cell exhaustion, enhance tumor control, and achieve dual antiviral/antitumor efficacy. This review summarizes oncoviral molecular mechanisms, integrates representative clinical trial evidence on the use of ICIs in virus-driven malignancies, and evaluates emerging combinatorial strategies. Future directions should emphasize biomarker-driven approaches and rational immunotherapy design to address the complex challenges in this evolving field.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"191 ","pages":"Article 118515"},"PeriodicalIF":7.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}