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Brain age estimation:premise,promise,and problems

Neural Regeneration Research 2025年第8期20卷 2313-2314页

作者： Jarrad Perron Ji Hyun Ko Graduate Program in Biomedical Engineering Price Faculty of EngineeringUniversity of ManitobaWinnipegMBCanada PrairieNeuro Research Centre Kleysen Institute for Advanced MedicineHealth Sciences CentreWinnipegMBCanada Department of Human Anatomy and Cell Science Rady Faculty of Health SciencesUniversity of ManitobaWinnipegMBCanada

Premise:The com bined effects of modern healthcare practices which prolong lifespan and declining birthrates have created unprecedented changes in age demographics worldwide that are especially pronounced in Japan,South Korea,Europe,and North *** old age is the most significant predictor of dementia,global healthcare systems must rise to the challenge of providing care for those with neurodegenerative disorders.

关键词： estimation providing birth

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Characterization of a new triaxial nanofiber membrane and osteogenic differentiation capacity of human bone marrow mesenchymal stem cells for bone repair

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Journal of Materials Research 2025年 1-18页

作者： Altundag-Erdogan, Özlem Çetinkaya, Hayrullah Çelebi-Saltik, Betül Altun, Belgin Şahin, Mehtap Mağden, Gamze Kara Öteyaka, Mustafa Özgür Department of Stem Cell Sciences Graduate School of Health Sciences and Center for Stem Cell Research and Development Hacettepe University Sihhiye Ankara06100 Turkey Department of Chemical Engineering Eskisehir Osmangazi University Eskişehir26040 Turkey Vocational School Health Services Hacettepe University Sihhiye Ankara06100 Turkey BUGAMED Biotechnology Industry and Trade Inc Eskişehir26380 Turkey Eskişehir Vocational School Electronics and Automation Eskisehir Osmangazi University Mechatronic Program Eskişehir26250 Turkey

A triaxial nanofiber membrane was developed using a custom triaxial nozzle during electrospinning. The membrane consisted of three layers (outer middle (PVA-Collagen Type I-BMP-2), and inner (PVA-nHAP)). TEM revealed the diameters of the outer, middle, and inner layers as 167.5, 142.6, and 119.3 nm, respectively. The triaxial nanofiber membrane exhibited superior tensile strength (36 MPa) and elastic modulus (2.5 GPa), along with a roughness of 359 nm and hydrophilic properties. In addition, it demonstrated a 200% swelling ratio and reduced bacterial colonization by 10.8-fold. Both Calcium deposition and ALP activity were significantly higher and increased expression of BSP (eightfold), OCN (13-fold), and OPN (488-fold) genes were observed in membrane + OST groups (p © The Author(s), under exclusive licence to The Materials Research Society 2025.

关键词： Bone

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The filopodial myosin DdMyo7 is a slow, calcium-regulated motor

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Journal of Biological Chemistry 2025年第5期301卷 108371页

作者： Eddington, Casey Titus, Margaret A. Department of Genetics Cell Biology and Development University of Minnesota MinneapolisMN United States Graduate Program in Biochemistry Molecular Biology and Biophysics University of Minnesota MinneapolisMN United States

MyTH4-FERM (MF) myosins are a family of molecular motors with critical roles in the formation and organization of thin membrane protrusions supported by parallel bundles of actin - filopodia, microvilli, and stereocilia. The amoeboid MF myosin DdMyo7 is essential for filopodia formation but its mechanism of action is unknown. The motor properties of a forced-dimer of the DdMyo7 motor were characterized using an in vitro motility assay to address this question. The DdMyo7 motor associates with two different light chains, the Dictyostelium calmodulins CalA and CalB, whose binding is shown to be sensitive to the presence of calcium. Total internal reflection fluorescence motility assays of the dimerized DdMyo7 motor reveal that it is a slow, processive motor that moves along actin at ∼ 40 nm/sec, and the activity of the motor is significantly reduced in the presence of Ca2+. The speed of DdMyo7 is similar to that of other Myo7 family members such as human Myo7A and fly DmMyo7A, but is at least 10-fold slower than the mammalian filopodial MF myosin, Myo10. The results show that evolutionarily distant native filopodial myosins can promote filopodia elongation using motors with distinct properties, revealing diverse mechanisms of myosin-based filopodia formation. © 2025 The Authors

关键词： Mammals

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MUC1 and MUC4 expression are inversely correlated and trigger immunological response and transport pathways in adult-type diffuse gliomas

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Computers in Biology and Medicine 2025年 187卷 109730-109730页

作者： Machado, Gabriel Cardoso Ferrer, Valéria Pereira Graduate Program in Pathological Anatomy Faculty of Medicine Rio de Janeiro Federal University Rio de Janeiro Brazil Laboratory of Cell and Molecular Biology of Tumors Department of Cell and Molecular Biology Biology Institute Fluminense Federal University Niterói Rio de Janeiro Brazil

Adult-type diffuse gliomas arise from glial or progenitor cells. These tumors are currently classified as astrocytoma isocitrate dehydrogenase (IDH)-mutant or IDH-mutant oligodendroglioma with co-deletion of chromosomal arms 1p and 19q, both of which could be either slow-growing tumors, or glioblastoma (GBM), which is a more aggressive tumor. Despite advances in diagnosis and treatment, the median survival time after GBM diagnosis remains low at approximately 15 months, with a 5-year overall survival (OS) rate of 6.8 %. Therefore, new biomarker and therapeutic target discoveries are required to improve prognosis. Mucin 1 (MUC1) and MUC4 are membrane-bound mucins and potential biomarkers of several tumors. However, the role of these mucins in adult gliomas has not been well explored. In this retrospective study, in silico analysis of data from patients with adult-type diffuse glioma revealed differential methylation and expression patterns of MUC1 and MUC4 between GBM and non-GBM groups. In the GBM group, decreased methylation and elevated expression of MUC1 were observed (r = −0.25, p © 2025 Elsevier Ltd

关键词： Methylation

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The association between urinary tract infections and diet: a literature review

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Discover Medicine 2025年第1期2卷 1-17页

作者： Çelik, Haluk Kozan, Esra Caf, Balım Bengisu Çebi, Gizem Koç, Murat Vivosens Inc. San Francisco USA Program of Stem Cell and Tissue Engineering Institute of Graduate Education Istinye University Istanbul Türkiye Department of Health Informatics University of Health Science Hamidiye Institute of Health Sciences Istanbul Türkiye

Urinary tract infections (UTIs) are a significant global health concern, affecting millions worldwide, with particular prevalence among specific vulnerable populations. Women of sexually active age, post-menopausal women, pregnant women, individuals with diabetes, catheterized patients, childs and older indivisuals face heightened risk due to various physiological, hormonal, and anatomical factors. While anatomical abnormalities and behavioral factors contribute to UTI susceptibility, the growing challenge of antibiotic resistance has necessitated exploration of alternative treatment approaches. Non-antibiotic interventions, including probiotics, cranberry products, and natural remedies, are gaining attention for their potential role in UTI prevention and management. Recent studies suggest the efficacy of probiotics and plant extracts in promoting urinary tract health and preventing bacterial colonization. Additionally, research highlights the importance of dietary factors, such as vitamin D and probiotic intake, in reducing UTI susceptibility. This review examines the emerging shift toward non-drug strategies, offering a more comprehensive approach to UTI management while addressing the pressing concern of antibiotic resistance.

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The pentameric chloride channel BEST1 is activated by extracellular GABA

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Proceedings of the National Academy of Sciences of the United States of America 2025年第16期122卷 e2424474122页

作者： Pant, Swati Tam, Stephanie W. Long, Stephen B. Structural Biology Program Memorial Sloan Kettering Cancer Center New York 10065 NY United States Graduate Program in Biochemistry and Structural Biology Cell and Developmental Biology and Molecular Biology Weill Cornell Medicine Graduate School of Medical Sciences New York 10065 NY United States Graduate Program in Physiology Biophysics and Systems Biology Weill Cornell Medicine Graduate School of Medical Sciences New York 10065 NY United States

Bestrophin-1 (BEST1) is a chloride channel expressed in the eye and other tissues of the body. A link between BEST1 and the principal inhibitory neurotransmitter γ-aminobutyric acid (GABA) has been proposed. The most appreciated receptors for extracellular GABA are the GABA_B G-protein-coupled receptors and the pentameric GABA_A chloride channels, both of which have fundamental roles in the central nervous system. Here, we demonstrate that BEST1 is directly activated by GABA. Through functional studies and atomic-resolution structures of human and chicken BEST1, we identify a GABA binding site on the channel’s extracellular side and determine the mechanism by which GABA binding stabilizes opening of the channel’s central gate. This same gate, “the neck,” is activated by intracellular [Ca²⁺], indicating that BEST1 is controlled by ligands from both sides of the membrane. The studies demonstrate that BEST1, which shares no structural homology with GABA_A receptors, is a GABA-activated chloride channel. The physiological implications of this finding remain to be studied. © 2025 the Author(s).

关键词： activation bestrophin chloride channel GABA receptor

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U1 snRNP regulates alternative promoter activity by inhibiting premature polyadenylation

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Molecular cell 2025年第10期85卷 1968-1981.e7页

作者： Kim, GyeungYun Carroll, Christine L. Wakefield, Zachary Peters Tuncay, Mustafa Fiszbein, Ana Biology Department Boston University Boston 02215 United States Graduate Program in Molecular Biology Cell Biology & Biochemistry Boston University Boston 02215 United States Graduate Program in Cell and Molecular Biology Boston University Boston 02215 United States Bioinformatics Program Faculty of Computing and Data Science Boston University Boston 02215 United States Center for Computing & Data Sciences Boston University Boston 02215 United States

Emerging evidence indicates that splicing factors mediate the close link between transcription and splicing. However, the mechanisms underlying this coupling remain unclear. U1 small nuclear ribonucleoprotein particle (U1 snRNP) not only initiates splicing but also plays a crucial role in preventing premature cleavage and polyadenylation, facilitating long-distance transcriptional elongation. Here, we show that U1 snRNP regulates alternative promoter activity in human cells by inhibiting premature polyadenylation. In genes carrying premature polyadenylation sites between two promoters, U1 snRNP inhibition with antisense oligonucleotides leads to a significant decrease in downstream promoter activity. Conversely, restoring U1 snRNP activity or inhibiting premature polyadenylation rescues downstream promoter activity. Mechanistically, U1 snRNP inhibition correlates with reduced chromatin accessibility, decreased RNA polymerase II serine 5 phosphorylation, and increased promoter-proximal pause at downstream promoters. Our findings support a model in which U1 snRNP favors productive elongation from upstream promoters, triggering downstream promoter activation by destabilizing nucleosomes and promoting promoter escape. © 2025 The Author(s)

关键词： alternative promoters dowsntream promoters promoter-proximal pause splicing factors splicing transcription transcription cooperativity transcription initiation transcription interfierence transcription start sites U1 snRNP

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Structure of the human TWIK-2 potassium channel and its inhibition by pimozide

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Proceedings of the National Academy of Sciences of the United States of America 2025年第19期122卷 e2425709122页

作者： Khanra, Nandish K. Wang, Chongyuan Delgado, Bryce D. Long, Stephen B. Structural Biology Program Memorial Sloan Kettering Cancer Center New York 10065 NY United States Graduate Program in Biochemistry and Structural Biology Cell and Developmental Biology and Molecular Biology Weill Cornell Medicine Graduate School of Medical Sciences New York 10065 NY United States

The potassium channel TWIK-2 is crucial for ATP-induced activation of the NLRP3 inflammasome in macrophages. The channel is a member of the two-pore domain potassium (K2P) channel superfamily and an emerging therapeutic target to mitigate severe inflammatory injury involving NLRP3 activation. We report the cryo-EM structure of human TWIK-2. In comparison to other K2P channels, the structure reveals an unusual “up” conformation of Tyr111 in the selectivity filter and a resulting SF1-P1 pocket behind the filter. Density for acyl chains is present in fenestrations within the transmembrane region that connects the central cavity of the pore to the lipid membrane. Despite its importance as a drug target, limited pharmacological tools are available for TWIK-2. A previous study suggested that the FDA-approved small molecule pimozide might inhibit TWIK-2. Using a reconstituted system, we show that pimozide directly inhibits the channel and we determine a cryo-EM structure of a complex with the drug. Pimozide displaces the acyl chains within the fenestrations and binds below the selectivity filter where it would impede ion permeation. The drug may access its binding site by lateral diffusion in the membrane, suggesting that other hydrophobic small molecules could have utility for inhibiting TWIK-2. The work defines the structure of TWIK-2 and provides a structural foundation for development of more specific inhibitors with potential utility as anti-inflammatory drugs. Copyright © 2025 the Author(s).

关键词： K2P channel K2P6 NLRP3 inflammasome potassium channel therapeutic

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Double-sided niche regulation in skin stem cell and cancer: mechanisms and clinical applications

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Molecular Cancer 2025年第1期24卷 1-61页

作者： Pham, Trang Thao Quoc Kuo, Yung-Che Chang, Wei-Ling Weng, Hao-Jui Huang, Yen-Hua International Ph.D. Program in Cell Therapy and Regenerative Medicine College of Medicine Taipei Medical University Taipei Taiwan TMU Research Center for Cell Therapy and Regeneration Medicine Taipei Medical University Taipei Taiwan Department of Dermatology Taipei Medical University-Shuang Ho Hospital New Taipei City Taiwan Department of Dermatology School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Graduate Institute of Clinical Medicine College of Medicine Taipei Medical University Taipei Taiwan Department of Biochemistry and Molecular Cell Biology School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei Taiwan

The niche microenvironment plays a crucial role in regulating the fate of normal skin stem cells (SSCs) and cancer stem cells (CSCs). Therapeutically targeting the CSC niche holds promise as an effective strategy; however, the dual effects of shared SSC niche signaling in CSCs have contributed to the aggressive characteristics of tumors and poor survival rates in skin cancer patients. The lack of a clear underlying mechanism has significantly hindered drug development for effective treatment. This article explores recent advances in understanding how niche factors regulate cell fate determination between skin stem cells and skin CSCs, along with their clinical implications. The dual roles of key components of the adhesive niche, including the dermo-epidermal junction and adherens junction, various cell types—especially immune cells and fibroblasts—as well as major signaling pathways such as Sonic hedgehog (Shh), Wingless-related integration site (Wnt)/β-catenin, YAP (Yes-associated protein)/TAZ (transcriptional coactivator with PDZ-binding motif), and Notch, are highlighted. Additionally, recent advances in clinical trials and drug development targeting these pathways are discussed. Overall, this review provides valuable insights into the complex interactions between skin cancer stem cells and their microenvironment, laying the groundwork for future research and clinical strategies.

关键词： Cancer stem cell Clinical trial Drug resistance Niche regulation Shh/Wnt/YAP/Notch signaling Skin stem cell Therapeutic targeting

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Advances in AAV capsid engineering: Integrating rational design, directed evolution and machine learning

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Molecular Therapy 2025年第5期33卷 1937-1945页

作者： Nisanov, Alan M. Rivera de Jesús, Julio A. Schaffer, David V. Department of Chemistry University of California Berkeley Berkeley 94720 CA United States Department of Chemical and Biomolecular Engineering University of California Berkeley Berkeley 94720 CA United States Department of Bioengineering University of California Berkeley Berkeley 94720 CA United States Graduate Program in Bioengineering University of California Berkeley San Francisco and University of California Berkeley 94720 CA United States Department of Neurological Surgery University of California San Francisco 94143 CA United States Department of Molecular and Cell Biology University of California Berkeley Berkeley 94720 CA United States

Adeno-associated virus (AAV) has emerged as a highly promising vector for human gene therapy due to its favorable safety profile, versatility, and ability to transduce a wide range of tissues. However, natural AAV serotypes have shortcomings, including suboptimal transduction efficiency, pre-existing immunity, and a lack of tissue specificity, that hinder their therapeutic potential. To address these challenges, significant efforts are being applied to engineer novel AAV capsids. Rational design leverages structural insights to enhance capsid properties, directed evolution enables unbiased selection of superior variants, and machine learning accelerates discovery by computational analysis of high-throughput screening results to enable predictive algorithms. These strategies have yielded novel capsids with improved transduction efficiency, reduced immunogenicity, and enhanced tissue targeting. Future advances that continue to integrate such multi-disciplinary approaches will further drive the clinical translation of AAV-based therapies. © 2025 The Authors

关键词： AAV directed evolution gene therapy high-throughput screening machine learning next generation sequencing NGS rational design

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