Pub Date : 2026-01-19DOI: 10.1016/j.jare.2026.01.050
Junaid Iqbal, Hui-Xuan Wu, Yan-Xuan Wu, Hong-Li Jiang, Long Li, Xuan-Yu Zhou, Yan-Hong Bu, Hou-De Zhou
{"title":"MetsObesity: a novel classification system for predicting 15-year cardiovascular risk in the UK Biobank population","authors":"Junaid Iqbal, Hui-Xuan Wu, Yan-Xuan Wu, Hong-Li Jiang, Long Li, Xuan-Yu Zhou, Yan-Hong Bu, Hou-De Zhou","doi":"10.1016/j.jare.2026.01.050","DOIUrl":"https://doi.org/10.1016/j.jare.2026.01.050","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"21 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146001283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-18DOI: 10.1016/j.jare.2026.01.049
Liangliang Liao, Cheng Lin, Adrian Kuzmanović, Nan Wang, Alexander Jans, Christian Penners, Kim Ohl, Sandra Johnen, Reka Geczy, Martin Rabel, Samuel Clarke, Aruna Balgi, Christian Liedtke, Matthias Bartneck
{"title":"Distinct effector functions and synergy of CAR mRNA-engineered T cells and macrophages in the clearance of CD19+ leukemia cells","authors":"Liangliang Liao, Cheng Lin, Adrian Kuzmanović, Nan Wang, Alexander Jans, Christian Penners, Kim Ohl, Sandra Johnen, Reka Geczy, Martin Rabel, Samuel Clarke, Aruna Balgi, Christian Liedtke, Matthias Bartneck","doi":"10.1016/j.jare.2026.01.049","DOIUrl":"https://doi.org/10.1016/j.jare.2026.01.049","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"177 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145995577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-18DOI: 10.1016/j.jare.2026.01.040
Shuang Liang, Wenxin Tao, Di Qu, Panpan Ji, Zhenzhen Hao, Mengying Wei, Guodong Yang, Xueying Zhou, Chen Wang, Lijun Yuan
Clonal hematopoiesis of indeterminate potential (CHIP), driven by somatic mutations (e.g., TET2), is an independent risk factor for atherosclerosis (AS). CHIP-mutant macrophages promote plaque inflammation, but targeted therapies are lacking. Crucially, whether these clones acquire immunogenic neoantigens—enabling immune clearance—remains unexplored. Objective: To investigate if Tet2-mutant cells in CHIP-associated AS develop immunogenic neoantigens and evaluate a neoantigen-targeting vaccine strategy. Methods: Tet2 was edited in hematopoietic cells via CRISPR/Cas9 and transplanted into Ldlr-/- mice fed a high-fat diet to model CHIP-accelerated AS. DNA and RNA sequencing of Tet2-mutant macrophages identified nonsynonymous mutations. Neoantigen immunogenicity was predicted in NetMHCpan. A therapeutic vaccine (GelVax) encapsulating mutant cell lysates (neoantigen source), GM-CSF (DC recruitment), and R848 (TLR agonist) within a biocompatible hydrogel was developed. Efficacy was assessed in the AS model. Results: Tet2 deficiency exacerbated atherosclerosis (+72% plaque area) and systemic inflammation. RNA-seq revealed 363 nonsynonymous mutations in mutant macrophages; 52 peptides showed high MHC-I binding affinity, confirming neoantigenicity. GelVax vaccination reduced aortic plaque burden by 45%, selectively cleared Tet2-mutant macrophages in plaques, attenuated systemic cytokines (TNF-α, IL-1β), improved plaque stability (↓ necrotic core, ↑ collagen), and protection was primarily CD8+ T-cell dependent. Conclusion: Tet2-mutant cells in CHIP-associated AS acquire immunogenic neoantigens. Leveraging these antigens via a hydrogel vaccine induces clone-specific CD8+ T cell responses, clears pathogenic macrophages, and ameliorates atherosclerosis. This validates mutant neoantigens as actionable targets for CHIP-driven cardiovascular disease
{"title":"Treatment of clonal hematopoiesis associated atherosclerosis via vaccine-based clearance of the mutant cells","authors":"Shuang Liang, Wenxin Tao, Di Qu, Panpan Ji, Zhenzhen Hao, Mengying Wei, Guodong Yang, Xueying Zhou, Chen Wang, Lijun Yuan","doi":"10.1016/j.jare.2026.01.040","DOIUrl":"https://doi.org/10.1016/j.jare.2026.01.040","url":null,"abstract":"Clonal hematopoiesis of indeterminate potential (CHIP), driven by somatic mutations (e.g., <em>TET2</em>), is an independent risk factor for atherosclerosis (AS). CHIP-mutant macrophages promote plaque inflammation, but targeted therapies are lacking. Crucially, whether these clones acquire immunogenic neoantigens—enabling immune clearance—remains unexplored. Objective: To investigate if <em>Tet2</em>-mutant cells in CHIP-associated AS develop immunogenic neoantigens and evaluate a neoantigen-targeting vaccine strategy. Methods: <em>Tet2</em> was edited in hematopoietic cells via CRISPR/Cas9 and transplanted into <em>Ldlr</em><sup>-/-</sup> mice fed a high-fat diet to model CHIP-accelerated AS. DNA and RNA sequencing of <em>Tet2</em>-mutant macrophages identified nonsynonymous mutations. Neoantigen immunogenicity was predicted in NetMHCpan. A therapeutic vaccine (GelVax) encapsulating mutant cell lysates (neoantigen source), GM-CSF (DC recruitment), and R848 (TLR agonist) within a biocompatible hydrogel was developed. Efficacy was assessed in the AS model. Results: <em>Tet2</em> deficiency exacerbated atherosclerosis (+72% plaque area) and systemic inflammation. RNA-seq revealed 363 nonsynonymous mutations in mutant macrophages; 52 peptides showed high MHC-I binding affinity, confirming neoantigenicity. GelVax vaccination reduced aortic plaque burden by 45%, selectively cleared <em>Tet2</em>-mutant macrophages in plaques, attenuated systemic cytokines (TNF-α, IL-1β), improved plaque stability (↓ necrotic core, ↑ collagen), and protection was primarily CD8<sup>+</sup> T-cell dependent. Conclusion: <em>Tet2</em>-mutant cells in CHIP-associated AS acquire immunogenic neoantigens. Leveraging these antigens via a hydrogel vaccine induces clone-specific CD8<sup>+</sup> T cell responses, clears pathogenic macrophages, and ameliorates atherosclerosis. This validates mutant neoantigens as actionable targets for CHIP-driven cardiovascular disease","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"57 73 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145995897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tumor-associated macrophages (TAMs) are a functionally heterogeneous population within the tumor microenvironments, exhibiting both anti-tumor and pro-tumor functions. Pro-tumorigenic TAMs can derive from peripheral monocytes or tissue-resident macrophages (TRMs). However, the epigenetic mechanisms driving the differentiation of these distinct cellular sources into specific TAM subtypes remain unclear.
Objectives
Here, we sought to define the epigenetic mechanisms that drive the divergent differentiation of monocyte and TRM-derived TAMs. Through a pan-cancer analysis, we map the regulatory cascade, from cis-regulatory elements and key transcription factors to the release of RNA Polymerase II (Pol II) pausing, that specifies TAM heterogeneity.
Methods
We performed single-cell epigenetic profiling of macrophages derived from various human cancers, precancerous lesions, and healthy adult and fetal tissues using publicly available datasets, coupled with single-cell multi-omics integration. Key findings were validated through multi-omics analysis of mouse bone marrow-derived macrophage and CRISPR-based functional assays using in vitro human cell culture models.
Results
We delineated the distinct epigenetic developmental trajectories by which peripheral monocytes and TRMs give rise to SPP1+ and C1QC + TAM, respectively. Along the monocyte-to-SPP1+ TAM trajectories, we identified PPARG, NFAT5 and MECP2 as pivotal regulators that promote pro-tumorigenic polarization. Conversely, the differentiation of TRMs to C1QC + TAMs was associated with regulators MAF, HES1 and PRDM1. Furthermore, we discovered a core transcriptional signature regulated by SPP1+ TAM-specific super-enhancers that is significantly associated with poor prognosis across 18 cancer types. Mechanistically, we demonstrated that these enhancers, such as HIPK2 enhancers, establish the pro-tumorigenic TAM state primarily by modulating Pol II pausing rather than by altering promoter accessibility of their target genes.
Conclusion
Our work delineates the epigenetic and transcriptional circuitry that establishes TAM heterogeneity as potential therapeutic levers to enhance cancer immunotherapy.
{"title":"Pan-cancer epigenetic landscape of human tumor-associated macrophages reveals crucial enhancers governing their heterogenous formation by Pol II pausing modulation","authors":"Chenchen Xiong, Hanhan Ning, Xiaoqiang Wang, Yushuang Xie, Zeyu Liu, Deqing Hu, Xin Gao","doi":"10.1016/j.jare.2026.01.048","DOIUrl":"https://doi.org/10.1016/j.jare.2026.01.048","url":null,"abstract":"<h3>Introduction</h3>Tumor-associated macrophages (TAMs) are a functionally heterogeneous population within the tumor microenvironments, exhibiting both anti-tumor and pro-tumor functions. Pro-tumorigenic TAMs can derive from peripheral monocytes or tissue-resident macrophages (TRMs). However, the epigenetic mechanisms driving the differentiation of these distinct cellular sources into specific TAM subtypes remain unclear.<h3>Objectives</h3>Here, we sought to define the epigenetic mechanisms that drive the divergent differentiation of monocyte and TRM-derived TAMs. Through a pan-cancer analysis, we map the regulatory cascade, from <em>cis</em>-regulatory elements and key transcription factors to the release of RNA Polymerase II (Pol II) pausing, that specifies TAM heterogeneity.<h3>Methods</h3>We performed single-cell epigenetic profiling of macrophages derived from various human cancers, precancerous lesions, and healthy adult and fetal tissues using publicly available datasets, coupled with single-cell multi-omics integration. Key findings were validated through multi-omics analysis of mouse bone marrow-derived macrophage and CRISPR-based functional assays using in vitro human cell culture models.<h3>Results</h3>We delineated the distinct epigenetic developmental trajectories by which peripheral monocytes and TRMs give rise to SPP1+ and C1QC + TAM, respectively. Along the monocyte-to-SPP1<sup>+</sup> TAM trajectories, we identified PPARG, NFAT5 and MECP2 as pivotal regulators that promote pro-tumorigenic polarization. Conversely, the differentiation of TRMs to C1QC + TAMs was associated with regulators MAF, HES1 and PRDM1. Furthermore, we discovered a core transcriptional signature regulated by SPP1+ TAM-specific super-enhancers that is significantly associated with poor prognosis across 18 cancer types. Mechanistically, we demonstrated that these enhancers, such as HIPK2 enhancers, establish the pro-tumorigenic TAM state primarily by modulating Pol II pausing rather than by altering promoter accessibility of their target genes.<h3>Conclusion</h3>Our work delineates the epigenetic and transcriptional circuitry that establishes TAM heterogeneity as potential therapeutic levers to enhance cancer immunotherapy.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"31 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145995509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lumbar CT and MRI scans are helpful for osteoporosis (OP) screening. Deep learning enhances the efficiency and accuracy of musculoskeletal quantification for OP screening.
Objectives
To develop a deep learning-based model (UNet3D) for musculoskeletal quantification from lumbar CT and MRI in OP patients, and to explore musculoskeletal relationship.
Materials
Retrospectively analyzing OP patients’ lumbar CT, MRI and DXA scans between January 2018 and August 2025 from two center, and UNet3D was developed based on U-Net to simultaneously segment L1-S1 vertebrae on CT and paraspinal muscles/intermuscular spaces on MRI. Performance was compared against U-Net, U2-Net, Mask-RCNN using pixel accuracy (PA), mean pixel accuracy (mPA), mean intersection over union (mIoU). Following automated HU values calculation within cancellous bone volume of interests (VOIs), we correlated L1-L4 HU values with T-scores and analyzed their relationship with muscle/space volumes across L1-S1, computing corresponding weighting coefficients.
Results
The study analyzed 410 OP patients (65 ± 10 years; 240 women) with 76,700 axial CT and 6030 axial T2 slices, including training (266), validation (76), internal test (38) and external test (30) sets. On the internal test set, UNet3D’s accuracy in CT (PA/mPA/mIoU, 0.984/0.849/0.760) and MRI (PA/mPA/mIoU, 0.973/0.849/0.724), outperformed U-Net/U2-Net/Mask R-CNN. On the external test set, UNet3D attained PA, mPA, and mIoU values of 0.971, 0.852, 0.741 in CT, and of 0.969, 0.834, 0.713 in MRI. HU values varied across vertebral VOIs, ranging from 80.33 HU (L2) to 195.14 HU (S1), and correlations existed between L1-L4 HU values and T-scores (r ≥ 0.85, P ＜ 0.05). Volumetric measurements across L1-S1 identified the psoas major as the largest muscle (173,317.68 mm3) and the quadratus lumborum as the smallest (65,167.78 mm3); among spaces, the psoas-vertebral was largest (124,301.86 mm3) and the quadratus lumborum-iliocostalis was smallest (29,676.63 mm3). Vertebral HU values correlated positively with muscle volumes (ω > 0) and negatively with space volumes and fatty infiltration (ω < 0).
Conclusion
UNet3D outperformed U-Net/U2-Net/Mask R-CNN on CT/MRI segmentation, enabling accurate musculoskeletal volume quantification in OP patients. Musculoskeletal correlations differed across spinal segments.
{"title":"Construction of musculoskeletal quantitative model based on deep learning and study of musculoskeletal relationship in patients with osteoporosis","authors":"Zhenzhen Guan, Yijin Wang, Shiyu Zhang, Yanyang Zhang, Liang Wang, Yixin Chen, Xuhua Lu","doi":"10.1016/j.jare.2026.01.037","DOIUrl":"https://doi.org/10.1016/j.jare.2026.01.037","url":null,"abstract":"<h3>Introduction</h3>Lumbar CT and MRI scans are helpful for osteoporosis (OP) screening. Deep learning enhances the efficiency and accuracy of musculoskeletal quantification for OP screening.<h3>Objectives</h3>To develop a deep learning-based model (UNet3D) for musculoskeletal quantification from lumbar CT and MRI in OP patients, and to explore musculoskeletal relationship.<h3>Materials</h3>Retrospectively analyzing OP patients’ lumbar CT, MRI and DXA scans between January 2018 and August 2025 from two center, and UNet3D was developed based on U-Net to simultaneously segment L1-S1 vertebrae on CT and paraspinal muscles/intermuscular spaces on MRI. Performance was compared against U-Net, U<sup>2</sup>-Net, Mask-RCNN using pixel accuracy (PA), mean pixel accuracy (mPA), mean intersection over union (mIoU). Following automated HU values calculation within cancellous bone volume of interests (VOIs), we correlated L1-L4 HU values with T-scores and analyzed their relationship with muscle/space volumes across L1-S1, computing corresponding weighting coefficients.<h3>Results</h3>The study analyzed 410 OP patients (65 ± 10 years; 240 women) with 76,700 axial CT and 6030 axial T2 slices, including training (266), validation (76), internal test (38) and external test (30) sets. On the internal test set, UNet3D’s accuracy in CT (PA/mPA/mIoU, 0.984/0.849/0.760) and MRI (PA/mPA/mIoU, 0.973/0.849/0.724), outperformed U-Net/U<sup>2</sup>-Net/Mask R-CNN. On the external test set, UNet3D attained PA, mPA, and mIoU values of 0.971, 0.852, 0.741 in CT, and of 0.969, 0.834, 0.713 in MRI. HU values varied across vertebral VOIs, ranging from 80.33 HU (L2) to 195.14 HU (S1), and correlations existed between L1-L4 HU values and T-scores (<em>r</em> ≥ 0.85, <em>P</em> ＜ 0.05). Volumetric measurements across L1-S1 identified the psoas major as the largest muscle (173,317.68 mm<sup>3</sup>) and the quadratus lumborum as the smallest (65,167.78 mm<sup>3</sup>); among spaces, the psoas-vertebral was largest (124,301.86 mm<sup>3</sup>) and the quadratus lumborum-iliocostalis was smallest (29,676.63 mm<sup>3</sup>). Vertebral HU values correlated positively with muscle volumes (ω > 0) and negatively with space volumes and fatty infiltration (ω < 0).<h3>Conclusion</h3>UNet3D outperformed U-Net/U<sup>2</sup>-Net/Mask R-CNN on CT/MRI segmentation, enabling accurate musculoskeletal volume quantification in OP patients. Musculoskeletal correlations differed across spinal segments.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"38 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145995510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metabolic vulnerabilities in ovarian cancer decoding the nexus between nutrient adaptation and therapy resistance","authors":"Xiaoyu Guo, Zongang Liu, Xiaoman Li, Bingzheng Zhou, Jingyi Chen","doi":"10.1016/j.jare.2026.01.047","DOIUrl":"https://doi.org/10.1016/j.jare.2026.01.047","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"383 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145995579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-18DOI: 10.1016/j.jare.2026.01.042
Dan Liu, YiDan Chen, WenZhao Li, ZhaoLi Li, YuPing Dai, Tong Li, PingYi Li, Hao Cheng, HaiLun He
Introduction
The stratum corneum represents a major barrier to transdermal drug delivery, while limited follicular activity contributes to hair loss disorders. Bacillus species, generally recognized as safe microorganisms, have broad applications in biotechnology and industry; however, its application in the cosmetics and pharmaceutical industries still faces certain challenges.
Objective
Bacillus sp. TC5 is a high-yield keratinase-producing strain. This study evaluated the dermatological potential of Bacillus sp. TC5 fermentation products, focusing on their dual functions in enhancing transdermal drug delivery and promoting hair growth through biochemical and molecular mechanisms.
Methods
Non-targeted metabolomics identified bioactive metabolites in TC5 fermentation products. Franz diffusion assays assessed their ability to enhance transdermal permeation of pharmaceuticals (5-fluorouracil, minoxidil, ketoprofen) and cosmetic agents (niacinamide, tripeptides, decapeptides). In vivo efficacy was examined in C57BL/6 mice through hair regrowth observation, follicle morphology (HE staining), and immunofluorescence staining for protein expression.
Results
TC5 fermentation products were non-toxic to HDFs, HaCaT cells (200–800 μg/mL), and DPCs (100–500 μg/mL) without inducing ROS. They markedly enhanced skin permeability, shortening lag time and increasing drug permeation. In vivo treatment improved follicle density and diameter, with increased ALP, K5, and Ki67 expression indicating dermal papilla activation. Mechanistically, the products stimulated the Wnt10b/β-catenin and VEGF/IGF-1 pathways, promoting follicular proliferation, angiogenesis, and epithelial renewal, while suppressing TGF-β1 and FGF5 and modulating BMP6 to prolong the anagen phase. Upregulation of keratin 14 and 17 strengthened hair shaft integrity.
Conclusion
Bacillus sp. TC5 fermentation products effectively promote hair regrowth and enhance transdermal drug absorption. These findings highlight TC5 metabolites as promising, eco-friendly candidates for developing novel skin penetration enhancers and cosmeceuticals for hair restoration and skin repair.
{"title":"Multi-targeted synergy of Bacillus sp. TC5 fermentation products for transdermal drug delivery and hair regeneration","authors":"Dan Liu, YiDan Chen, WenZhao Li, ZhaoLi Li, YuPing Dai, Tong Li, PingYi Li, Hao Cheng, HaiLun He","doi":"10.1016/j.jare.2026.01.042","DOIUrl":"https://doi.org/10.1016/j.jare.2026.01.042","url":null,"abstract":"<h3>Introduction</h3>The stratum corneum represents a major barrier to transdermal drug delivery, while limited follicular activity contributes to hair loss disorders. <em>Bacillus</em> species, generally recognized as safe microorganisms, have broad applications in biotechnology and industry; however, its application in the cosmetics and pharmaceutical industries still faces certain challenges.<h3>Objective</h3><em>Bacillus</em> sp. TC5 is a high-yield keratinase-producing strain. This study evaluated the dermatological potential of <em>Bacillus</em> sp. TC5 fermentation products, focusing on their dual functions in enhancing transdermal drug delivery and promoting hair growth through biochemical and molecular mechanisms.<h3>Methods</h3>Non-targeted metabolomics identified bioactive metabolites in TC5 fermentation products. Franz diffusion assays assessed their ability to enhance transdermal permeation of pharmaceuticals (5-fluorouracil, minoxidil, ketoprofen) and cosmetic agents (niacinamide, tripeptides, decapeptides). In vivo efficacy was examined in C57BL/6 mice through hair regrowth observation, follicle morphology (HE staining), and immunofluorescence staining for protein expression.<h3>Results</h3>TC5 fermentation products were non-toxic to HDFs, HaCaT cells (200–800 μg/mL), and DPCs (100–500 μg/mL) without inducing ROS. They markedly enhanced skin permeability, shortening lag time and increasing drug permeation. In vivo treatment improved follicle density and diameter, with increased ALP, K5, and Ki67 expression indicating dermal papilla activation. Mechanistically, the products stimulated the Wnt10b/β-catenin and VEGF/IGF-1 pathways, promoting follicular proliferation, angiogenesis, and epithelial renewal, while suppressing TGF-β1 and FGF5 and modulating BMP6 to prolong the anagen phase. Upregulation of keratin 14 and 17 strengthened hair shaft integrity.<h3>Conclusion</h3><em>Bacillus</em> sp. TC5 fermentation products effectively promote hair regrowth and enhance transdermal drug absorption. These findings highlight TC5 metabolites as promising, eco-friendly candidates for developing novel skin penetration enhancers and cosmeceuticals for hair restoration and skin repair.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"9 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145993340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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