Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences最新文献

{"title":"[Clinical value of cerebrospinal fluid metagenomic next-generation sequencing in the diagnosis of neonatal intracranial infection].","authors":"Lingchen Li, Lizhong Du","doi":"10.3724/zdxbyxb-2025-0965","DOIUrl":"10.3724/zdxbyxb-2025-0965","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the diagnostic performance of cerebrospinal fluid metagenomic next-generation sequencing (mNGS) for neonatal intracranial infections and its value in clinical decision-making.</p><p><strong>Methods: </strong>A retrospective observational study was conducted, enrolling neonates admitted to the Children's Hospital, Zhejiang University School of Medicine from 2020 to 2025 with suspected intracranial infection who underwent cerebrospinal fluid mNGS. The sensitivity of mNGS and its concordance with cerebrospinal fluid culture-quantitative polymerase chain reaction (qPCR) were calculated. Clinical impact was evaluated using predefined criteria, and samples were categorized accordingly into positive-impact and no-impact groups to explore independent factors influencing the positive impact of mNGS on clinical decision-making.</p><p><strong>Results: </strong>Among 61 neonates with suspected intracranial infection, 48 were confirmed. Pathogens were identified in 18 cases, of which 9 were detected exclusively by mNGS, accounting for 50% of etiological diagnoses. The sensitivity of mNGS was 31.3% (95%CI: 18.7%-46.3%), higher than that of cerebrospinal fluid culture-qPCR at 18.8% (95%CI: 8.9%-32.6%), though the difference was not statistically significant (<i>P</i>=0.15). The positive and negative concordance rates between mNGS and cerebrospinal fluid culture-qPCR were 66.7% (95%CI: 29.9%-92.5%) and 76.9% (95%CI: 60.7%-88.9%), respectively. mNGS positively influenced clinical decisions in 23 patients: 12 cases with positive results guided etiological diagnosis and treatment adjustment, while 11 cases with negative results led to antibiotic de-escalation or discontinuation. Multivariate analysis identified a positive mNGS result as an independent factor associated with positive clinical impact (OR=22.127, <i>P</i><0.01).</p><p><strong>Conclusions: </strong>Cerebrospinal fluid mNGS provides positive support in etiological diagnosis and clinical decision-making for neonatal intracranial infection.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":"55 7","pages":"675-682"},"PeriodicalIF":0.0,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Advances in innate immune-mediated neuroinflammatory mechanisms of migraine].","authors":"Wanting Zhu, Pinglong Xu, Yutong Liu","doi":"10.3724/zdxbyxb-2026-0029","DOIUrl":"10.3724/zdxbyxb-2026-0029","url":null,"abstract":"<p><p>Migraine is a highly disabling neurological disorder in which activation of the trigeminovascular system and the ensuing peripheral and central sensitization are major pathological foundations for pain initiation, recurrent attacks, and disease chronification. In recent years, innate immune-mediated sterile neuroinflammation has emerged as a key mechanism linking trigeminal neurovascular system activation to maladaptive remodeling of nociceptive pathways. During the early phase of a migraine attack, trigeminal nerve endings release calcitonin gene-related peptide, pituitary adenylate cyclase-activating polypeptide, and substance P, thereby inducing meningeal vasodilation, plasma protein extravasation, mast cell degranulation, and immune-cell recruitment, which collectively enhance the excitability of peripheral nociceptors. These peripheral inflammatory signals are subsequently transmitted to the spinal trigeminal nucleus caudalis and higher-order central nervous system regions, where they drive sustained activation of microglia and astrocytes, disruption of neurotransmitter homeostasis, and remodeling of neuronal excitability, ultimately maintaining central sensitization. Repeated stimulation may convert a transient neuroimmune response into persistent low-grade activation. Concerted glial activation, blood-brain barrier dysfunction, and positive-feedback interactions between neuropeptides and inflammatory mediators are thought to drive migraine chronification. At the molecular level, endogenous danger-associated molecular patterns, including extracellular adenosine triphosphate and high-mobility group protein 1, activate Toll-like receptor-nuclear factor-κB signaling and NLRP3 inflammasome pathways, which act as major molecular drivers for initiating and amplifying the inflammatory cascade. Accordingly, targeting upstream components of innate immune signaling has shown preclinical potential to reverse hyperalgesia and central sensitization, thereby providing a new direction for the development of next-generation disease-modifying therapies. This review elucidates the central roles of innate immune signaling pathways in the initiation, maintenance, and chronification of migraine-associated neuroinflammation, and discusses recent advances and current challenges in the translational development of therapeutic strategies targeting these pathways, aiming to provide new insights into the immunopathological mechanisms of migraine and to facilitate the development of disease-modifying treatment approaches.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":"55 7","pages":"662-674"},"PeriodicalIF":0.0,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Mechanisms of cGAS-STING-mediated chronic inflammation and targeted interventions in brain aging].","authors":"Haoyue Zhang, Danqi Yu, Pinglong Xu, Qirou Wu","doi":"10.3724/zdxbyxb-2026-0033","DOIUrl":"10.3724/zdxbyxb-2026-0033","url":null,"abstract":"<p><p>Brain aging is a critical risk factor for various neurodegenerative diseases, with chronic neuroinflammation being one of its core features. The innate immune cGAS-STING signaling pathway, acting as a key sensor of endogenous damage, has emerged as a nexus linking cellular senescence to chronic inflammation. During brain aging, genomic damage and mitochondrial dysfunction facilitate the aberrant accumulation of cytosolic double-stranded DNA. Together with transposable element activation and intercellular propagation of cGAMP, these factors drive sustained activation of the cGAS-STING signaling pathway. This activation not only drives the transcription of interferons and pro-inflammatory cytokines but also accelerates brain functional decline by reshaping neural cell physiology, as manifested by the polarization of glial cells toward a pro-inflammatory phenotype and the release of a senescence-associated secretory phenotype, as well as the induction of cellular stress and apoptosis in neurons, ultimately leading to disruption of synaptic homeostasis and loss of specific neuronal subpopulations. Consequently, targeting the cGAS-STING signaling pathway has emerged as a potential strategy to mitigate brain aging. This review systematically summarizes the sources and mechanisms of cGAS-STING activation during brain aging, with a particular focus on dissecting the molecular mechanisms by which this pathway drives and sustains inflammatory responses and functional remodeling across distinct neural cell types. Furthermore, we explore its implications in age-related neurodegenerative diseases and potential interventional strategies, aiming to provide a theoretical basis and novel perspectives for blocking aging-associated inflammatory cascades in the brain.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":"55 7","pages":"652-661"},"PeriodicalIF":0.0,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[<b>\"</b>Triple-hit<b>\"</b> pathogenic mechanism of Leber hereditary optic neuropathy].","authors":"Kai Wang, Siqi Li, Yongming Zhang, Minxin Guan","doi":"10.3724/zdxbyxb-2025-0868","DOIUrl":"10.3724/zdxbyxb-2025-0868","url":null,"abstract":"<p><p>Leber hereditary optic neuropathy (LHON) is a typical mitochondrial genetic optic neuropathy predominantly affecting retinal ganglion cells and leading to irreversible visual damage. Although a single primary mitochondrial DNA (mtDNA) mutation provides the basis for the disease, it cannot fully explain its incomplete penetrance, male predominance, and clinical heterogeneity. Based on familial genetic analysis and functional studies, this review summarizes the \"triple-hit\" pathogenic mechanism of LHON. The first hit consists of primary mtDNA mutations, such as m.11778G>A, m.14484T>C, and m.3460G>A, which primarily impair respiratory chain complex Ⅰ function and weaken mitochondrial energy metabolism. The second hit involves mtDNA modifier variants, mtDNA haplogroup backgrounds, and nuclear modifier gene variants, which lower the threshold for disease onset and affect the penetrance in primary mtDNA mutation carriers. The third hit consists of non-genetic triggers, including exogenous exposures (such as smoking, alcohol consumption, and exposure to mitochondrial-toxic drugs) and endogenous physiological abnormalities (such as sex hormone-related differences in mitochondrial protection), which further weaken mitochondrial compensatory capacity and ultimately precipitate retinal ganglion cell damage. This review provides an integrated framework for understanding the pathogenic mechanism of LHON, aiming to serve as a reference for the screening of high-risk individuals, genetic counseling, risk prediction, and mechanism-driven clinical research of LHON.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"683-690"},"PeriodicalIF":0.0,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148206422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Molecular mechanisms of chronic gastric mucosal inflammation induced by <i>Helicobacter pylori</i> via immune evasion].","authors":"Shiying Wu, Mingyang Hu, Pinglong Xu, Fei Zhang","doi":"10.3724/zdxbyxb-2026-0014","DOIUrl":"10.3724/zdxbyxb-2026-0014","url":null,"abstract":"<p><p><i>Helicobacter pylori</i> (<i>H. pylori</i>) persistently colonizes the gastric mucosa and induces sustained inflammation, making it a major driver of the development and progression of chronic gastritis, peptic ulcer disease, and gastric cancer. Its pathogenicity does not rely on direct tissue damage inflicted by a single virulence factor, but rather on the coordinated actions of multiple factors, including cytotoxin-associated gene A (CagA), vacuolating cytotoxin A (VacA), lipopolysaccharide, and urease that disrupt the gastric epithelial barrier and perturb mucosal immune homeostasis. Concurrently, <i>H. pylori</i> modulates key immune recognition pathways, such as nuclear factor κB, mitogen-activated protein kinase, the NLRP3 inflammasome, and others, to reshape both innate and adaptive immune responses, thereby facilitating bacterial persistence and chronic infection. With deepening knowledge of <i>H. pylori</i>-host crosstalk, therapeutic strategies have evolved from mere pathogen elimination toward modulation of bacterial pathogenic processes and restoration of host immune homeostasis. In recent years, virulence-targeted approaches directed against CagA, VacA, the type Ⅳ secretion system, and colonization-associated factors, along with host-directed therapies that target inflammatory signaling cascades, have garnered increasing interest. This review summarizes the molecular underpinnings of <i>H.pylori</i>-host interactions, with a focus on virulence factor-mediated pathogenicity, host immune regulation, and the establishment of chronic inflammation. Moreover, we discuss emerging therapeutic modalities targeting pathogen-host interfaces and outline future directions, aiming to offer insights for precision prevention and treatment of <i>H. pylori</i>-associated diseases.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":"55 7","pages":"624-637"},"PeriodicalIF":0.0,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149082082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Mechanism of Huangqin Qingre Chubi Capsule in inhibiting inflammation and proliferation of fibroblast-like synoviocyte in rheumatoid arthritis].","authors":"Yuedi Hu, Jian Liu","doi":"10.3724/zdxbyxb-2025-0685","DOIUrl":"10.3724/zdxbyxb-2025-0685","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;To clarify the role of the ALKBH5&lt;i&gt;/&lt;/i&gt;circ_0091685&lt;i&gt;/&lt;/i&gt;eIF4A3 axis in rheumatoid arthritis fibroblast-like synoviocyte (RA-FLS) and to investigate whether a traditional Chinese medicine preparation Huangqin Qingre Chubi Capsule (HQC) regulates inflammation and proliferation of RA-FLS through this axis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Differentially expressed genes (DEGs) between RA patients and healthy individuals were screened based on microarray datasets from the Gene Expression Omnibus (GEO) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify related biological processes and pathways. A co-culture model of peripheral blood mononuclear cells and RA-FLS was established. Through overexpression or silencing of &lt;i&gt;ALKBH5&lt;/i&gt;, circ_0091685, and &lt;i&gt;EIF4A3&lt;/i&gt;, combined with site-directed mutation of the &lt;i&gt;N&lt;/i&gt;⁶-methyladenosine (m⁶A) sites within circ_0091685, we verified whetherALKBH5 targets eIF4A3 by mediating m⁶A modification of circ_0091685, thereby affecting RA-FLS inflammation and proliferation. Meanwhile, an adjuvant-induced arthritis rat model was established to observe the therapeutic effects of HQC &lt;i&gt;in vivo&lt;/i&gt;. Furthermore, HQC-containing serum was applied to RA-FLS to explore the underlying mechanism involving the ALKBH5/circ_0091685/eIF4A3 axis. Cell proliferation was assessed by 5-ethynyl-2 ´-deoxyuridine (EdU) staining; inflammatory cytokine levels were measured by ELISA; expression of &lt;i&gt;EIF4A3&lt;/i&gt; and circ_0091685 was detected by RT-qPCR; protein expression of ALKBH5 and eIF4A3 was analyzed by Western blotting; the binding between circ_0091685andeIF4A3 was validated by RNA immunoprecipitation (RIP); total RNA m⁶A levels and m⁶A modification on circ_0091685 were detected by colorimetric assay and methylated RNA immunoprecipitation-qPCR, respectively; and histopathological changes in rat knee joints were observed using hematoxylin and eosin staining, safranin O-fast green staining, and toluidine blue staining.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;&lt;i&gt;ALKBH5&lt;/i&gt; and &lt;i&gt;EIF4A3&lt;/i&gt; wereamong the top 20 DEGs between RA patients and healthy individuals. GO analysis indicated enrichment of methylation-related biological processes, and KEGG analysis identified enriched pathways including the IL-17 signaling pathway. Compared with the &lt;i&gt;ALKBH5&lt;/i&gt; silencing control group, the &lt;i&gt;ALKBH5&lt;/i&gt;-silenced group showed decreased expression of ALKBH5, circ_0091685, eIF4A3, reduced levels of IL-6, IL-17A, IL-23 and TNF-α, and a lower relative number of EdU-positive cells (all &lt;i&gt;P&lt;/i&gt;&lt;0.01), whereas the &lt;i&gt;ALKBH5&lt;/i&gt; overexpression group exhibited the opposite effects. Compared with the &lt;i&gt;ALKBH5&lt;/i&gt; overexpression+circ_0091685 control group, the &lt;i&gt;ALKBH5&lt;/i&gt; overexpression+circ_0091685 mutant group had significantly reduced IL-6, IL-17A, IL-23, and TNF-α levels (all &lt;i&gt;P&lt;/i&gt;&lt;0.01). RIP assays confirmed thatcirc_0091685 specifically binds to eIF4A3. Sil","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":"55 7","pages":"587-601"},"PeriodicalIF":0.0,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Regulatory mechanisms of post-translational modifications in inflammasome signaling: a review].","authors":"Chenyang He, Pinglong Xu, Shengduo Liu","doi":"10.3724/zdxbyxb-2026-0035","DOIUrl":"10.3724/zdxbyxb-2026-0035","url":null,"abstract":"<p><p>Inflammasomes are central platforms of innate immunity that sense pathogenic and damage-associated signals and drive the maturation of proinflammatory cytokines as well as pyroptotic cell death. Their aberrant activation contributes to a wide range of pathological conditions, including inflammatory, autoimmune, metabolic, and neurological diseases. Recent studies have uncovered a dynamic regulatory network of post-translational modifications (PTMs) that governs the priming, assembly, activation, and degradation of inflammasome signaling. Ubiquitination and deubiquitination primarily control the stability, complex assembly, and degradation of inflammasome components. Phosphorylation and dephosphorylation regulate NLRP3 conformational switching, its interaction with NIMA-related kinase 7, and ASC speck formation through kinase-phosphatase crosstalk, while also modulating NLRC4 and Pyrin inflammasome activation. Acetylation and deacetylation, SUMOylation and deSUMOylation affect inflammasome assembly, protein degradation, and pyroptotic execution in a site- or isoform-specific manner. Collectively, these PTM networks determine the maturation and release of IL-1β and IL-18, as well as the intensity of gasdermin D-mediated pyroptosis. This review summarizes the major types of PTMs, their regulatory mechanisms, and the disease-related advances involving key inflammasome components. It also discusses therapeutic strategies and translational challenges associated with targeting these modification networks, with the aim of providing a reference for mechanistic studies and precision interventions in inflammation-associated diseases.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":"55 7","pages":"613-623"},"PeriodicalIF":0.0,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149082074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Recent advances on effects of sleep quality, duration, and circadian rhythm disruption on <i>in vitro</i> fertilization-embryo transfer outcomes].","authors":"Jingyi Yin, Jingyan Song, Zhengao Sun","doi":"10.3724/zdxbyxb-2025-0856","DOIUrl":"https://doi.org/10.3724/zdxbyxb-2025-0856","url":null,"abstract":"<p><p>Despite the widespread use of <i>in vitro</i> fertilization and embryo transfer (IVF-ET), the clinical pregnancy rate per oocyte retrieval cycle remains approximately 25%, making the identification of modifiable factors to improve success rates remains a clinical priority. Sleep disorders are highly prevalent among IVF-ET patients and their partners, with reported rates up to 91.1%, representing a substantial but often overlooked risk factor for IVF-ET outcomes. This review systematically examines the impact of sleep quality, sleep duration, and circadian rhythm on IVF-ET outcomes and discusses the underlying biological mechanisms. Current evidence indicates a significant positive correlation between sleep quality and pregnancy outcomes; women with good sleep quality have a 12% higher probability of live birth, whereas poor sleep quality is an independent risk factor for pregnancy failure in females and for reduced semen quality in males. The relationship between sleep duration and reproductive outcomes follows a non-linear inverted U-shaped pattern, with 7-8 hours identified as the optimal range. Deviations from this range-particularly sleep deprivation-are primarily associated with lower oocyte yield and reduced oocyte maturity. Moreover, circadian misalignment impairs embryo implantation rates and sperm motility by disrupting clock gene expression. Mechanistically, these sleep disturbances compromise gamete quality and endometrial receptivity through three major pathways: disruption of the hypothalamic-pituitary-gonadal axis homeostasis, induction of oxidative stress and inflammation, and interference with the normal rhythmic secretion of reproductive hormones. Intervention studies show that both pharmacological and non-pharmacological approaches can improve sleep, but their effects on IVF-ET outcomes vary. Melatonin may enhance embryo quality and pregnancy outcomes via antioxidant activity; behavioral interventions have been shown to increase live birth rates; and acupuncture may improve clinical pregnancy rates. Psychological and behavioral interventions can ameliorate sleep and emotional status, yet their direct benefit on pregnancy outcomes remains uncertain. In males, regular sleep schedules combined with antioxidant therapy may improve sperm quality. In conclusion, this review consolidates the evidence linking sleep quality, duration, and circadian rhythm to IVF-ET outcomes and their biological bases. Optimizing sleep patterns represents an important and modifiable strategy to improve IVF-ET success. Incorporating sleep health management throughout the entire IVF-ET treatment cycle may offer a low-cost, non-invasive adjunct to enhance pregnancy outcomes.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"1-11"},"PeriodicalIF":0.0,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148550654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Cytochalasin B-Induced adipose stem cell-derived nanovesicles promote hair follicle regeneration via activation of the β-catenin signaling pathway].","authors":"Lei Wang, Yiwen Liu, Peiyun Cai, Xuerui Mao, Tian Tian, Lei Cao","doi":"10.3724/zdxbyxb-2025-0780","DOIUrl":"10.3724/zdxbyxb-2025-0780","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the regulatory effects of adipose stem cell (ADSC)-derived cytochalasin B-induced nanovesicles (CINVs) on the biological functions of dermal papilla cells (DPCs) and on hair follicle cycle transition, and to explore the underlying molecular mechanisms.</p><p><strong>Methods: </strong>CINVs were prepared from ADSCs. Their effects on DPC proliferation, migration, and apoptosis were assessed <i>in vitro</i>. A mouse depilation model was used to evaluate the ability of CINVs to promote the transition of hair follicles from telogen to anagen. Western blotting, hematoxylin-eosin (HE) staining, and immunofluo-rescence analyses were performed to assess the activation of β-catenin-related signaling pathways and to elucidate the molecular mechanisms of CINV-mediated hair follicle regeneration.</p><p><strong>Results: </strong>CCK-8 assays showed that CINVs at 40 and 60 μg/mL significantly enhanced DPC proliferation. Wound healing assays (at 40 μg/mL) confirmed that CINVs markedly promoted DPC migration. Western blotting revealed that, compared with the control group, CINV treatment significantly increased the expression of phosphorylated GSK-3β (p-GSK-3β, <i>P</i><0.05) and upregulated β-catenin, the core effector of the canonical Wnt/β-catenin pathway (<i>P</i><0.01). Moreover, cyclin D1 (a positive regulator of cell cycle progression) expression was elevated (<i>P</i><0.05), and the levels of phosphorylated AKT (p-AKT, associated with cell survival) and phosphorylated ERK (p-ERK, associated with cell proliferation) were significantly increased (both <i>P</i><0.05). The Bcl-2/Bax ratio (an anti-apoptotic index) was also increased. <i>In vivo</i>, CINV-treated mice displayed darkened dorsal skin and enlarged hair bulb diameters, along with elevated proportions of β-catenin- and Ki67-positive cells. These effects were significantly attenuated by co-administration of the β-catenin inhibitor MSAB.</p><p><strong>Conclusions: </strong>ADSC-derived CINVs effectively regulate the biological functions of DPCs and promote the transition of hair follicles from telogen to anagen, primarily through activation of the β-catenin signaling pathway.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"1-11"},"PeriodicalIF":0.0,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148398088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Gilteritinib enhances the inhibitory effect of dabrafenib on anaplastic thyroid carcinoma cells by suppressing the AXL signaling pathway].","authors":"舒 亭 许, 雨 晨 高, 艳 婷 段, 瑞 敏 梁, 磊 朱","doi":"10.3724/zdxbyxb-2025-0799","DOIUrl":"https://doi.org/10.3724/zdxbyxb-2025-0799","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the inhibitory effect of combined gilteritinib and dabrafenib treatment on anaplastic thyroid cancer (ATC) cells and its underlying mechanisms.</p><p><strong>Methods: </strong>The BRAF V600E-mutant ATC cell line 8505C and the BRAF wild-type ATC cell line KHM-5M were treated with various concentrations of dabrafenib (0, 40, 80, 120, 160, 320 nmol/mL) and gilteritinib (0, 0.1, 0.2, 0.4, 0.6, 1.0, 2.0 μmol/mL), alone or in combination. Cell proliferation and viability were assessed using the CCK-8 assay, and the IC₅₀ was calculated. The inhibitory effect on cell migration was evaluated using the Transwell assay. To examine the impact of treatment sequence on the combined efficacy, ATC cells were pretreated with either dabrafenib or gilteritinib for 1, 4, or 6 h, followed by the addition of the other drug and further incubation for a total of 24 h, after which cell viability was measured. Western blotting was performed to detect the expression of proteins related to apoptosis, proliferation, AXL, and the RAS/RAF/MEK/ERK pathway. Furthermore, AXL siRNA knockdown experiments were conducted to validate the molecular mechanism by which AXL mediates the gilteritinib-enhanced sensitivity of ATC cells to dabrafenib.</p><p><strong>Results: </strong>Both gilteritinib and dabrafenib inhibited ATC cell proliferation in a concentration-dependent manner. Gilteritinib significantly enhanced the inhibitory effect of dabrafenib on ATC cell viability, and the combination also showed significantly greater inhibition of cell migration than either monotherapy. Mechanistically, in both ATC cell lines, compared with dabrafenib alone, the combination with gilteritinib consistently further downregulated the expression of AXL/p-AXL, RAS, and RAF, and reduced total ERK/MEK protein levels. Simultaneously, the combination reversed the aberrant activation of p-MEK/p-ERK induced by dabrafenib monotherapy, promoted the expression of apoptosis-related proteins, and decreased the expression of proliferation-related proteins. Moreover, upon silencing of AXL, the IC₅₀ value of dabrafenib in the AXL-knockdown group was significantly reduced.</p><p><strong>Conclusions: </strong>Gilteritinib enhances the antitumor efficacy of dabrafenib against ATC cells by inhibiting the AXL signaling pathway and delaying MAPK pathway reactivation<b>.</b></p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"1-11"},"PeriodicalIF":0.0,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148398067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}