Journal of Biomedical Science最新文献

{"title":"Osmotin-derived 9-amino-acid peptide alleviates α-synuclein and MPTP-induced glial cell activation mediated neuroinflammation, protecting dopaminergic neurons in Parkinson's disease mice brain.","authors":"Kyonghwan Choe, Muhammad Tahir, Min Hwa Kang, Hyun Young Park, Riaz Ahmad, Tae Ju Park, Myeong Ok Kim","doi":"10.1186/s12929-026-01215-4","DOIUrl":"10.1186/s12929-026-01215-4","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) is the second most common neurodegenerative disorder, categorized by the loss of dopaminergic neurons in the brain's Substantia Nigra pars compacta (SNpc) due to α-synuclein (α-syn) aggregation, leading to reduced dopamine levels in the striatum. This research study evaluates the neuroprotective potential of the novel peptide osmotin-derived 9-amino-acid (Os_9aa, C-T-Q-G-P-C-G-P-T) against α-syn (neuron-specific enolase promoter human alpha-synuclein (NSE-hαSyn)) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD models.</p><p><strong>Methods: </strong>Human neuroblastoma SH-SY5Y cells were employed as an in vitro model, while NSE-hαSyn (α-synuclein) transgenic mice and MPTP-treated mice were used as in vivo models of PD. MPTP was administered intraperitoneally (30 mg/kg) once daily for five consecutive days. Mice were immunized with Os_9aa (15 mg/kg, i.p., twice weekly for five weeks), followed by behavioral assessments including open field test, wire hang test, pole test, and rotarod test, and biochemical analysis using the Triplex Assay, western blotting, and confocal microscopy.</p><p><strong>Results: </strong>Our study demonstrated that the novel peptide Os_9aa enhanced cell viability, reduced cytotoxicity, and apoptosis in SH-SY5Y neuroblastoma cells. Os_9aa attenuated synucleinopathy-related pathology in NSE-hαSyn transgenic mice and MPTP-induced PD mouse models. Current findings also highlighted the therapeutic potential of Os_9aa in mitigating behavioral deficits observed in NSE-hαSyn and MPTP mouse models of PD. Furthermore, Os_9aa administration effectively restored key dopaminergic markers, including tyrosine hydroxylase (TH), vesicular monoamine transporter 2 (VMAT2), and dopamine transporter (DAT). Additionally, it reduced neuroinflammation by decreasing the activation of glial cells-ionized calcium-binding adaptor molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP), as well as pro-inflammatory cytokines, such as phosphorylated nuclear factor-κB (p-NF-кB), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), in the striatum and SNpc regions. Furthermore, Os_9aa mitigated oxidative stress (OS) by upregulating the expression of nuclear factor erythroid-related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1), and improved cognitive performance.</p><p><strong>Conclusion: </strong>Collectively, these findings highlight the neuroprotective potential of the Os_9aa, which counteracts α-synuclein- and MPTP-induced neurotoxicity by reducing oxidative stress, glial activation, and neuroinflammation. This multifaceted protection preserves neuronal integrity in both the NSE-hαSyn transgenic and MPTP-induced PD mouse models, underscoring Os_9aa as a promising therapeutic candidate for modifying PD pathogenesis.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":"13"},"PeriodicalIF":14.5,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12833940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146052362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting mechanosensitive cannabinoid receptor 1 with isoflavone prodrugs attenuates atherosclerotic endothelial dysfunction.","authors":"Dai-Jung Chung, Shao-Peng Chen, Wei-Hsuan Liu, Chia-Yu Liu, Nan-Wei Su, Chen Hsu, Hsin-Ya Tsai, Kai-Chien Yang, Cho-Kai Wu, Sheng-Wei Lin, Jiun-Jie Shie, Ming-Tao Zhao, Tzu-Tang Wei","doi":"10.1186/s12929-026-01214-5","DOIUrl":"10.1186/s12929-026-01214-5","url":null,"abstract":"<p><strong>Background: </strong>Despite therapeutic advances, atherosclerosis remains a major global health challenge. Most current treatments target systemic risk factors rather than the diseased vascular wall. Our previous work identified genistein, a soy isoflavone, as a cannabinoid receptor 1 (CB1) antagonist capable of suppressing CB1-mediated vascular inflammation and atherosclerosis. However, its poor water solubility and low oral bioavailability limit clinical application.</p><p><strong>Purpose: </strong>We aimed to develop water-soluble, orally bioavailable CB1 antagonists for atherosclerosis and to investigate the role of endothelial CB1 in hemodynamic regulation.</p><p><strong>Methods: </strong>RNA-sequencing datasets from the NCBI GEO repository were analyzed to assess CB1 expression in atherosclerotic patients. Apolipoprotein E-deficient (Apoe^-/-) mice with or without partial carotid artery ligation (PCAL) were used to model acute and chronic atherosclerosis. A cone-and-plate viscometer was employed to simulate disturbed flow. A ligand-based high-throughput virtual screening approach combined with SWEETLEAD chemical database analysis was used to discover new CB1 antagonists. A biotransformation-based strategy was used to generate isoflavone monophosphate prodrugs.</p><p><strong>Results: </strong>We found CB1 was upregulated in atherosclerotic lesions from patients and mice, and in endothelial cells exposed to disturbed flow. Mechanistically, this was driven by ZNF610 and Spi1 binding and KLF4 dissociation at the CB1 promoter. Daidzein, a soy isoflavone structurally similar to genistein, was identified as a novel CB1 antagonist. To enhance solubility and bioavailability, we developed genistein 7-O-phosphate (G7P) and daidzein 7-O-phosphate (D7P). Pharmacological treatment with these isoflavone monophosphates or genetic CB1 ablation reversed disturbed flow-induced endothelial dysfunction and endothelial-to-mesenchymal transition (EndMT). Oral administration of G7P and D7P significantly reduced atherosclerotic plaque formation in mice.</p><p><strong>Conclusions: </strong>This is the first study to identify transcriptional regulators that drive endothelial CB1 upregulation in response to disturbed flow. We further demonstrated that isoflavone monophosphates ameliorate disturbed flow-induced endothelial dysfunction and EndMT via CB1 inhibition, offering promising oral therapeutics for atherosclerosis.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":"12"},"PeriodicalIF":14.5,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12822132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146010633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mod-SE(2): a geometric deep learning framework for brain tumor classification and segmentation in MRI images.","authors":"Clara Lavita Angelina, Fu-Ren Xiao, Sunil Vyas, Pan-Chyr Yang, Hsuan-Ting Chang, Yuan Luo","doi":"10.1186/s12929-025-01213-y","DOIUrl":"10.1186/s12929-025-01213-y","url":null,"abstract":"<p><strong>Background: </strong>Accurate classification and segmentation of brain tumors in MRI scans are essential for diagnosis and treatment planning. However, the heterogeneous morphology of brain tumors, including irregular shapes, sizes, and spatial variability, makes this task highly challenging. Traditional convolutional neural networks (CNNs) lack rotational and translational invariance, which limits their ability to generalize across different orientations.</p><p><strong>Methods: </strong>This study introduces a geometric deep learning framework called Modified Special Euclidean (Mod-SE(2)), which integrates geometric priors to enhance spatial consistency and reduce reliance on data augmentation. By incorporating symmetry-preserving group convolutions and spatial priors, Mod-SE(2) improves the robustness in tumor classification (namely Mod-Cls-SE(2)) and segmentation (mentioned as Mod-Seg-SE(2)). Unlike conventional CNNs, geometric deep learning encodes roto-translation symmetry directly into the architecture. This addresses the spatial variability and orientation sensitivity that are common in MRI-based diagnostics. Mod-SE(2) was evaluated on three MRI datasets and two other medical image datasets for classification and segmentation tasks. It incorporates lifting layers, group convolutions, and feature recalibration. It was benchmarked against U-Net, NN U-Net, VGG16, VGG19, and ResNet architectures.</p><p><strong>Results: </strong>Mod-Cls-SE(2) achieved an average classification accuracy of 0.914, outperforming ResNet101 with 0.682, VGG16 with 0.705, and their variants. In the binary classification of five tumor types (AVM, Meningioma, Pituitary, Metastases, and Schwannoma) from the private dataset, the model achieved an accuracy of 0.935 and a precision of 0.960 for pituitary tumors and a precision of 0.96. For segmentation tasks, Mod-Seg-SE(2) achieved a dice coefficient of 0.9503 and an IoU of 0.9616 on the BraTS2020 dataset. This result exceeds those of U-Net and NN U-Net with dice scores of 0.797 and 0.815, respectively. The model also reduced inference time and demonstrated strong computational performance.</p><p><strong>Conclusions: </strong>Mod-SE(2) uses geometric priors to improve the spatial consistency, efficiency, and interpretability in brain tumor analysis. Its symmetry-aware design enables better generalization across tumor shapes and outperforms traditional methods across all key metrics. The Mod-SE(2) CNN ensures accurate boundary delineation, supporting neurosurgical planning, intraoperative navigation, and downstream applications such as Monte Carlo-based radiotherapy simulations and PET-MRI co-registration. Future work will extend the model to 3D volumes and validate its clinical readiness.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":"11"},"PeriodicalIF":14.5,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12794471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CCL5/RANTES signaling in inflammation dysregulation after mild traumatic brain injury.","authors":"Man-Hau Ho, Yih-Jeng Tsai, Yu-Hsuan Lee, Yi-Chen Hsieh, Chia-Hung Yen, Jia-Yi Wang, Thierry Burnouf, Chia-Yen Chen, Wen-Cheng Lin, Yun Wang, Yung-Hsiao Chiang, Barry J Hoffer, Szu-Yi Chou","doi":"10.1186/s12929-025-01203-0","DOIUrl":"10.1186/s12929-025-01203-0","url":null,"abstract":"<p><strong>Background: </strong>Mild traumatic brain injury (mTBI) is the most prevalent form of brain injury. Secondary damage following mTBI contributes to neuronal degeneration by promoting neuroinflammation, amyloid accumulation, and oxidative stress (OS). Microglia exhibit dual roles after injury, contributing to both pro-inflammatory (M1) and anti-inflammation/neuroprotective (M2) responses. Targeting microglial polarization may therefore represent a therapeutic strategy for mitigating secondary damage after TBI.</p><p><strong>Methods: </strong>A weight-drop mTBI model (30 g, 100 cm) was applied to both C57BL/6 (wild-type) and CCL5 knockout (CCL5-KO) mice. Microglial activation was assessed at 7-, 14-, 21-, and 28-days post-injury using RT-qPCR, immunohistochemistry, and western blotting. Oxidative stress in tissue was detected by Hydroxyprobe™ labeling, ROS detection, NADPH oxidase activity assay, and antioxidant expression. Recombinant CCL5 (rCCL5) was administered intranasally to evaluate its effect on post-injury inflammation. Cortical tissue was subjected to liquid chromatography-tandem mass spectrometry (LC-MS/MS) for proteomic profiling. In vitro, BV2 microglial cells were treated with H₂O₂ to model OS. The effects of rCCL5 on cell viability, inflammatory gene expression, and phagocytic activity were assessed via MTT assay, immunocytochemistry, flow cytometry, and RT-qPCR. Pharmacological inhibitors targeting CCR1, CCR3, and CCR5 were used to delineate receptor-specific signaling pathways.</p><p><strong>Results: </strong>rCCL5 significantly reduced oxidative stress in both neurons and microglia and enhanced expression of antioxidant enzymes such as GPX1, SOD1, and SOD2 in injured cortices. Proteomic analysis revealed upregulation of immune regulatory and phagocytosis-related pathways following rCCL5 treatment. In vitro, rCCL5 conferred cytoprotection against H₂O₂-induced cell death and promoted M2-like microglial polarization. Blockade of CCR5, but not CCR3, abrogated CCL5-induced M2 differentiation, whereas both CCR3 and CCR5 were required for enhanced phagocytosis. CCL5-induced NFATc2 activation was mediated primarily via CCR5.</p><p><strong>Conclusions: </strong>These findings demonstrate that CCL5 modulates microglial polarization and attenuates oxidative stress in the injured brain through a CCR5-dependent mechanism. Targeting the CCL5-CCR5 signaling axis may offer a promising therapeutic strategy for improving outcomes after mTBI.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":"10"},"PeriodicalIF":14.5,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12784600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145933556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding collagen cues: the interplay of integrins and discoidin domain receptors in health and disease.","authors":"Paola Trono, Ilenia Masi, Flavia Ottavi, Laura Rosanò","doi":"10.1186/s12929-025-01211-0","DOIUrl":"10.1186/s12929-025-01211-0","url":null,"abstract":"<p><p>The extracellular matrix (ECM) provides critical biochemical and biophysical cues that regulate cell behavior in health and disease. Collagens dominate in abundance and structural importance, shaping tissue-specific ECM signatures that guide cellular behavior. Two major and distinct transmembrane receptor families, integrins and discoidin domain receptors (DDRs), serve as primary sensors for collagens, yet they employ fundamentally distinct binding mechanisms and signaling kinetics. While both can activate shared downstream pathways, their functional interplay remains complex and context-dependent, with the potential to fine-tune cellular responses to ECM cues. This review deciphers the nuanced crosstalk between integrin β1 and DDRs, with a particular focus on the understudied DDR2, across physiological and pathological processes. We discuss how this interplay, which evolves from cooperative to compensatory or even antagonistic signaling, is influenced by variables,  such as tissue specificity, developmental timing, and pathological context, dictating cell adhesion, migration, and ECM remodeling. Key examples include DDRs acting as allosteric regulators to license integrin activation, their partnership in mechanotransduction during development, and their divergent roles in aging tissues, where altered collagen mechanics shift the receptor hierarchy. In pathology, the DDR-integrin axis is pivotal in fibrosis and cancer, influencing fibroblast activation, drug resistance, metastatic outgrowth, and immune suppression within the tumor microenvironment. Notably, the receptors can function both independently and synergistically; for instance, DDR2 in cancer-associated fibroblasts regulates integrin-mediated mechanosignaling to promote metastasis, while in other contexts, both receptors activate distinct survival pathways. Understanding the signaling dynamics and mechanisms of these receptors is necessary for deciphering how cells interpret ECM signals and how these mechanisms contribute to disease progression, especially in those diseases marked by collagen remodeling. This comprehension is crucial for developing novel therapeutic strategies. Emerging evidence suggests that combined targeting DDRs and integrins can synergistically overcome ECM-mediated therapy resistance, enhance immune infiltration, and reprogram pathological microenvironments, offering a promising approach for treating fibrosis and collagen-rich cancers.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":"8"},"PeriodicalIF":14.5,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12771863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor-on-chip's alliance with molecular pathology against metastatic disease.","authors":"Emma Di Carlo","doi":"10.1186/s12929-025-01209-8","DOIUrl":"10.1186/s12929-025-01209-8","url":null,"abstract":"<p><strong>Background: </strong>Cancer is the second leading cause of death worldwide. While significant progress has been made in early detection and treatment, metastasis remains the major cause of cancer-related morbidity and mortality. In the last decade the rate of long-term survivorship of metastatic cancer has continued to improve and overcoming resistance to therapy has now become a challenge. Developing strategies to prevent and treat metastatic disease is a priority for public health and requires a thorough understanding of the mechanisms driving progression of a specific patient's tumor and the rapid identification of targetable cancer drivers and drug resistance genes.</p><p><strong>Discussion: </strong>Custom bioprinted tumors, which recreate the interactions between tumors and surrounding tissues, can be integrated into organ-on-chip platforms, and leveraging molecular pathology and OMICS data, can provide highly realistic patient-specific models. These biomimetic tools enable the investigation of metastasis organotropism, the identification of therapeutic targets and the design of drug administration protocols to prevent metastasis and to overcome resistance. Benefits, limitations, and challenges to address for an efficient and routine application of this cutting-edge approach, together with the role of Artificial-Intelligence (AI) in managing the complex datasets generated by OMICS technologies will be highlighted in this review, as well as their real-life implications and evolutionary prospects.</p><p><strong>Conclusion: </strong>Applying patient-derived bioprinted tumors and organs for clinical purpose and developing standardized 4D and 5D bioprinting protocols would allow assessment of cancer response to treatments in a dynamic and faithfully reconstructed microenvironment. Integration of advanced molecular diagnostics and multi-OMICS data, with customized small-scale tumor models, assisted by AI-powered tools, requires a multidisciplinary framework. This integrated approach can upgrade clinical management of metastatic diseases, by accelerating the identification of actionable biomarkers and resistance mechanisms for timely therapy adjustments, thus enabling tailored treatment regimens based on individual tumor behavior.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":"9"},"PeriodicalIF":12.1,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12771749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PHGDH at the crossroads: metabolic plasticity, metastatic paradoxes, and therapeutic reconnaissance in cancer.","authors":"Liang Hao, Bai-Qiang Li, Shi-Yang Lu, Zhong-Cai An, Zheng-Yuan Yin, Zhen-Xian Du, Hua-Qin Wang","doi":"10.1186/s12929-025-01205-y","DOIUrl":"10.1186/s12929-025-01205-y","url":null,"abstract":"<p><p>Phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme of the serine biosynthesis pathway (SSP), is a central metabolic hub and multifunctional oncoprotein that drives tumorigenesis through both canonical and non-canonical mechanisms. This review outlines the multi-level regulation of PHGDH, covering epigenetic remodeling (DNA hypomethylation, H3K4me3/H3K36me3 dynamics), transcriptional control (ATF4, MYC, EWS-FLI1), post-transcriptional fine-tuning (m⁶A/m⁵C modifications, RNA-binding proteins), and post-translational modifications (ubiquitination, methylation, phosphorylation). Together, these regulatory layers allow cancer cells to adapt metabolically to microenvironmental stress. Beyond its fundamental role in supplying nucleotides, maintaining redox homeostasis, and supporting one-carbon metabolism, PHGDH also performs moonlighting function. For example, its translocation to the nucleus inhibits PARP1 to sustain oncogenic transcription, while its presence in mitochondria helps remodel electron transport chains to promote metastasis. Critically, PHGDH exhibits a therapeutic paradox wherein its inhibition can synergize with chemotherapy, radiotherapy, and immunotherapy across diverse malignancies, yet tumors develop resistance via metabolic plasticity, or by selection of PHGDH-low metastatic clones. The clinical translation of PHGDH inhibitors is further challenged by inherent neurotoxicity risks, as neurons rely on de novo serine synthesis. To address these challenges, we propose a precision roadmap that integrates spatial multi-omics, AI-driven allosteric inhibitor design, dynamic biosensing (e.g., ¹⁸F-metabolite PET), and biomarker-stratified clinical trials. By reconciling the dual nature of PHGDH biology, we can transform this metabolic linchpin from a confounding paradox into a clinically actionable vulnerability.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":"5"},"PeriodicalIF":12.1,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12766945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbiome modulation of tumorigenesis and immune responses.","authors":"Yuning Chen, Ying Fang, Zibai Lyu, Yanxin Tian, Siyue Niu, Yan-Ruide Li, Lili Yang","doi":"10.1186/s12929-025-01208-9","DOIUrl":"10.1186/s12929-025-01208-9","url":null,"abstract":"<p><p>The microbiome has emerged as a critical, context-dependent regulator of tumorigenesis and anticancer immunity, capable of either promoting cancer progression or protecting against malignancy. This dual role is mediated by multiple interconnected mechanisms-including chronic inflammation, modulation of immune responses, and alterations in host metabolic signaling. These microbiome-cancer interactions vary across organs, influencing malignancies in the colon, breast, lung, and beyond. Clinically, the microbiome significantly affects patient responses to cancer therapies, particularly immunotherapies such as immune checkpoint blockade (ICB) and chimeric antigen receptor (CAR)-T cell therapy. Although emerging therapeutic strategies aimed at modulating the microbiome have shown promising early results, challenges remain, including individual microbiome variability and the dynamic interplay between the immune system and microbial communities. Nevertheless, harnessing the microbiome holds significant potential to transform precision oncology, offering personalized cancer prevention and treatment strategies tailored to each patient's unique microbial ecosystem.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":"4"},"PeriodicalIF":12.1,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12766967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GASDERMIN D-mediated pyroptosis as a therapeutic target in TAU-dependent frontotemporal dementia mouse model.","authors":"Ignacio Silva-Llanes, Lilia A Smith, Aaron Abdelkader-Guillén, José Jiménez-Villegas, David Sarrió, Gema Moreno-Bueno, Isabel Lastres-Becker","doi":"10.1186/s12929-025-01210-1","DOIUrl":"10.1186/s12929-025-01210-1","url":null,"abstract":"<p><strong>Background: </strong>Recent research has revealed a strong connection between neuroinflammation and TAU protein-related neurodegeneration. A key discovery shows that the NLRP3 inflammasome, when activated, can significantly impact TAU pathology and subsequent neuronal death. This process involves pyroptosis, a lytic form of programmed cell death driven by inflammasome activation, leading to GASDERMIN D (GSDMD) cleavage and the subsequent release of inflammatory molecules IL-1β and IL-18. In this study, we explore the role of pyroptosis and GSDMD in Alzheimer's disease (AD) and tauopathy models, focusing on the TAU-induced neuroinflammatory process and its correlation with synaptic plasticity loss.</p><p><strong>Methods: </strong>Hippocampal tissue from AD patients at Braak stage II-III has been analyzed using qPCR to assess pyroptosis-related gene expression. To determine the role of TAU in pyroptosis and neuroinflammation, we used two different models: one based on intracerebral injection of an adeno-associated virus that specifically overexpresses TAU in the neurons of the hippocampus (AAV-TAU^P301L), and a transgenic mouse model Tg-TAU^P301S at 8 and 10 months of age. Gene expression, protein levels, and neuroinflammation markers were evaluated using qPCR and immunofluorescence. Additionally, both genetic (GSDMD-deficient mice) and pharmacological (dimethyl fumarate, DMF) interventions targeting pyroptosis have been explored to assess their impact on neuroinflammation and synaptic plasticity.</p><p><strong>Results: </strong>AD patients exhibited increased expression of pyroptosis-related genes, supporting the involvement of pyroptosis in neurodegeneration. Furthermore, TAU overexpression induced pyroptosis in both mouse models, and GSDMD protein levels increased alongside reactive microglial morphology. Our data supports that TAU-induced neuroinflammation correlated with synaptic plasticity impairment. GSDMD deficiency significantly reduced pyroptosis-related markers associated to TAU, but unexpectedly worsened synaptic plasticity deficits, suggesting GSDMD may play a dual role in inflammation and synaptic function. Finally, we showed that DMF treatment suppressed pyroptosis gene expression, reduced GSDMD levels, and alleviated neuroinflammation, correlating with improved synaptic marker expression.</p><p><strong>Conclusion: </strong>Our findings demonstrate that TAU-induced pyroptosis contributes to neuroinflammation and synaptic dysfunction. While GSDMD inhibition mitigates inflammation, its absence exacerbates synaptic impairment, highlighting its complex role in tauopathies. Our results indicate that DMF treatment could offer a promising therapeutic avenue to modulate pyroptosis and neuroinflammation, and restore synaptic integrity in tauopathies.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":"6"},"PeriodicalIF":12.1,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12766953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular insights into the antimicrobial and cardiometabolic functions of Lactobacillus crispatus isolated from the reproductive tract microbiota of Indian women.","authors":"Shriram Mahajan, N Lekshmi, Proxima Dhiman, Manjari Gupta, Pallavi Mudgal, Rajni Yadav, Sudheer Arava, Shinjini Bhatnagar, Nitya Wadhwa, Yashwant Kumar, Daizee Talukdar, Bhabatosh Das, Sanjay K Banerjee","doi":"10.1186/s12929-025-01207-w","DOIUrl":"10.1186/s12929-025-01207-w","url":null,"abstract":"<p><strong>Background: </strong>Lactobacillus crispatus is a dominant member of the healthy female reproductive tract microbiota, contributing to mucosal homeostasis and pathogen exclusion. Numerous studies have highlighted the protective effects of L. crispatus against both intestinal and genital infections. In the present study, we build on this foundation to investigate the broader health-promoting properties of L. crispatus, focusing on its antimicrobial and metabolic functions; and its protective roles in hepatic and cardiometabolic disorders.</p><p><strong>Methods: </strong>Three L. crispatus strains were selected from a panel of sixty isolates based on comprehensive genome mining analyses described in our previous publication. In the present study, we generated complete genome data for these three strains, and delineated biosynthetic pathways including their capacity for antimicrobial peptide production, lactic acid biosynthesis, short chain fatty acid synthesis and biogenic amine production. The antimicrobial activity of these isolates was assessed via agar well-diffusion assay and time-kill assay. Their ability to survive gastric pH and bile stress was evaluated through acid and bile salt tolerance assays. Further, to assess metabolic benefits, anti-steatotic and cardioprotective effects were examined in a preclinical diet-induced mouse model of cardiometabolic disorder.</p><p><strong>Results: </strong>Complete genome analysis of L. crispatus strains revealed multiple antimicrobial peptide (AMP) biosynthetic gene clusters, including several novel loci associated with bacteriocins. Metabolic profiling identified pathways for bile salt metabolism, folate biosynthesis and short chain fatty acids production. Cell-free culture supernatants exhibited broad-spectrum antibacterial activity, particularly against Escherichia coli, Enterobacter hormaechei, Staphylococcus aureus and Staphylococcus haemolyticus. Further, the strains tolerated gastric pH 2 and physiological bile stress of 0.3% suggesting potential for oral administration. In vivo, oral administration of L. crispatus (10⁸ CFU) daily for 2 weeks followed by twice-weekly for 12 weeks significantly reduced hepatic steatosis, improved insulin sensitivity and cardiac function in a diet-induced cardiometabolic disorder mouse model. This is the first report demonstrating the cardiometabolic protective potential of L. crispatus.</p><p><strong>Conclusions: </strong>L. crispatus confers diverse health benefits through pathogen resistance functions and modulation of host metabolic pathways. These findings support its potential as a novel biotherapeutic for preventing and managing hepatic and cardiometabolic disorders, extending its therapeutic relevance beyond reproductive health.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"33 1","pages":"7"},"PeriodicalIF":12.1,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12766959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}