Advanced biology最新文献

{"title":"Chaperone-Mediated Autophagy: A Critical Regulator of Neuroinflammation and Neurodegeneration.","authors":"Ying-Ying Han, Xin-Yue Huang, Ying Su, Jing-Jing Ma, Jin Wu","doi":"10.1002/adbi.202500191","DOIUrl":"https://doi.org/10.1002/adbi.202500191","url":null,"abstract":"<p><p>Neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), are characterized by hallmark pathological features such as the accumulation of misfolded proteins and neuroinflammation. Chaperone-mediated autophagy (CMA), a selective lysosomal pathway, facilitates the degradation of proteins containing KFERQ-like motifs via the receptor lysosome-associated membrane protein type 2A (LAMP2A). In the recent review, the pivotal role of CMA in regulating proteostasis and modulating inflammatory responses is highlighted. This commentary explores the multifaceted roles of CMA in neurodegenerative disease progression, emphasizing its involvement in age-related decline, feedback loops between CMA dysregulation and neurodegeneration, and potential as a therapeutic target. Emerging CMA activators and the challenges of modulating CMA for clinical use are also discussed.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e00191"},"PeriodicalIF":3.2,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the Cellular Effects of GALC Dosing in Enzyme Replacement Therapy for Krabbe Disease Supports the Role of Nanomedicine.","authors":"Ambra Del Grosso, Sara Carpi, Laura Colagiorgio, Miriam De Sarlo, Mariacristina Gagliardi, Marco Cecchini","doi":"10.1002/adbi.202500147","DOIUrl":"https://doi.org/10.1002/adbi.202500147","url":null,"abstract":"<p><p>Krabbe disease (KD) is a lysosomal storage disorder characterized by severe neurodegeneration and demyelination. It is caused by mutations in the galactosylceramidase (GALC) gene, leading to the accumulation of psychosine, a neurotoxic metabolite. This study presents an optimized workflow for the production and characterization of recombinant murine GALC (rm-GALC) from HEK293T cells, aiming to improve the feasibility of enzyme replacement therapy (ERT) for KD. An affinity chromatography protocol is refined to purify His-tagged rm-GALC, followed by buffer exchange and concentration steps to produce a stable and active enzyme suitable for subsequent in vitro applications. The purified rm-GALC is characterized for enzymatic activity, purity, and stability using SDS-PAGE, immunoblotting, and dynamic light scattering (DLS). In vitro assays reveal dose-dependent enzymatic activity recovery in KD primary cells upon rm-GALC administration, with no adverse effects on cell viability up to the physiological GALC dose. Additionally, GALC treatment at the physiological dose restored autophagic function in KD cells, as shown by LC3 and p62 marker analyses, confirming its compatibility with lysosomal-autophagic pathways. Conversely, supra-physiological GALC administration resulted in decreased viability and autophagy impairment. Finally, the feasibility of loading GALC into a polymeric nanovector based on stabilized reverse micelles is investigated. These findings highlight the critical importance of precise GALC dose regulation in developing a safe and effective enzyme replacement therapy (ERT) strategy for Krabbe disease (KD), further supporting the potential of a nanovector-mediated ERT approach.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e00147"},"PeriodicalIF":3.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fecal Microbiota Transplantation Modulates Th17/Treg Balance via JAK/STAT Pathway in ARDS Rats.","authors":"Dongwei Zhang, Biying Dong, Jie Chen, Zhenqiang Zhang, Weitong Zeng, Longxiong Liao, Xia Xiong, Xuejun Qin, Xianming Fan","doi":"10.1002/adbi.202500028","DOIUrl":"https://doi.org/10.1002/adbi.202500028","url":null,"abstract":"<p><p>This study evaluated the therapeutic effects of fecal microbiota transplantation (FMT) on lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) in rats. The study focused on the balance of T-helper 17 (Th17) and regulatory T (Treg) cells, as well as the modulation of the JAK/STAT pathway. This study established a rat ARDS model using intranasal LPS instillation, administering interventions such as FMT, Treg cell depletion, and JAK inhibitors. Assessments included histopathological examination of lung and intestinal tissues, flow cytometry for Th17 and Treg cell proportions, qPCR and Western blot for gene and protein expression, ELISA for inflammatory cytokines, and correlation analysis using Spearman's method for cytokine-immune cell interactions. Results indicated that FMT and JAK inhibitors significantly reduce lung damage induced by LPS, reduced alveolar destruction and inflammation, restored Th17/Treg balance, and inhibited JAK/STAT pathway activity. Notably, FMT decreased pro-inflammatory cytokines (IL-2, IL-6, IL-8, IL-17A, IL-23, TGF-β1) and increased anti-inflammatory cytokines (IL-10, IL-35) in serum. Spearman correlation analysis indicated that FMT restored immune balance by modulating the interactions between cytokines and immune cells. In conclusion, FMT effectively alleviates lung and intestinal injury in LPS-induced ARDS rat models by modulating Th17/Treg balance and inhibiting JAK/STAT pathway activity, demonstrating promising therapeutic potential for ARDS treatment.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e00028"},"PeriodicalIF":3.2,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting RAGE with Nanobodies for Molecular Imaging of Cancers and Alzheimer's Disease.","authors":"Guangfeng Liang, Fujing Wang, Wei Xiong, Guangwei Shi, Junling Yuan, Yang Li, Hongyan Zhang, Yanmei Xing, Shan Jin, Kongjun Yang, Zhongliang Dai, Jichao Sun, Zhijie Li, Jianhong Wang","doi":"10.1002/adbi.202400617","DOIUrl":"https://doi.org/10.1002/adbi.202400617","url":null,"abstract":"<p><p>The receptor for advanced glycation end products (RAGE) is a multifunctional cell surface receptor implicated in aging and the progression of chronic diseases, including cancer and Alzheimer's disease. Its interaction with advanced glycation end products (AGEs) promotes cellular stress and inflammation, underscoring the diagnostic and therapeutic relevance of targeting RAGE. In this study, we explored the potential of nanobodiessingle-domain antibodies known for high specificity, strong affinity, and deep tissue penetrationas molecular tools for RAGE-targeted applications. Using a phage display library, a panel of RAGE-specific nanobodies were isolated and characterized. Binding activity and affinity were evaluated through enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) assays. Among them, nanobody NbF8 demonstrated the highest affinity and specificity toward RAGE. In vitro, NbF8 selectively bound RAGE-expressing cells, while in vivo imaging in renal carcinoma and Alzheimer's disease mouse models confirmed its targeted accumulation in RAGE-overexpressing tumors and brain tissues. These findings highlight NbF8 as a promising molecular imaging agent for RAGE-associated diseases. This study supports the potential of RAGE-targeting nanobodies in both diagnostic imaging and therapeutic development, offering a novel approach for precision medicine in conditions driven by RAGE signaling.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e00617"},"PeriodicalIF":3.2,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lithocholic Acid, Calorie Restriction, and Halting Aging.","authors":"Cade Ward, Michael M Shahid, Grace Hohman, Mohamed A Eldeeb","doi":"10.1002/adbi.202500110","DOIUrl":"https://doi.org/10.1002/adbi.202500110","url":null,"abstract":"<p><p>While aging is a natural biological process, it is associated with a greater risk for multiple diseases, including cancer, neurodegeneration, and cardiovascular disease. Thus, it is important to study the biochemical mechanisms involved in aging to understand how to treat and prevent these health conditions. The discovery that calorie restriction (CR) promoted longevity in various organisms is a major breakthrough for aging research. Molecular studies of CR have revealed that it mediates its anti-aging effects by activating key signaling pathways, including the AMPK pathway. This pathway is important for regulating various processes, including energy homeostasis, metabolism, and proteostasis. Despite the advantages associated with CR, this practice can have detrimental effects, including decreased liver, body, and muscle mass. Additionally, CR is difficult to track and maintain, limiting its long-term potential. Interestingly, direct activation of the AMPK pathway offers a potential approach to increase longevity and quality of life without dietary restrictions. Remarkably, a recent discovery revealed that lithocholic acid (LCA), a metabolite from bile acid, could directly activate the AMPK pathway. Activation of the AMPK pathway by LCA leads to the beneficial effects of CR without the negative effects. These recent findings point to the possibility that supplementation of specific doses of LCA could offer a novel approach to induce anti-aging pathways that lead to increased longevity and improved quality of life.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e00110"},"PeriodicalIF":3.2,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precision Medicine in ICH Unveiling the Superior Predictive Power of a Joint Model.","authors":"Fa Wu, YuLin Yang, TingTing Wu, JinPing Sheng, FeiZhou Du, JianHao Li, ZhiWei Zuo, JunFeng Zhang, Rui Jiang, Peng Wang","doi":"10.1002/adbi.202400833","DOIUrl":"https://doi.org/10.1002/adbi.202400833","url":null,"abstract":"<p><p>This study examined the effectiveness of a combined model using non-contrast computed tomography (NCCT) imaging, clinical data, and radiomics for predicting early hematoma enlargement in patients with spontaneous intracerebral hemorrhage. The study involved 232 patients with primary cerebral hemorrhage who met the inclusion criteria at the General Hospital of the Western Theater Command, PLA, between January 2018 and December 2023. Imaging and clinical features were compared, radiomic features were extracted from head CT scans, and a multivariate logistic regression model identified key imaging markers and clinical features. Univariate and multivariate logistic regression models were used for dimensionality reduction of radiomic features and to develop a radiomic signature/model. Patients were split into training and validation sets in a 7:3 ratio. Then, NCCT, clinical, radiomics, and combined NCCT-clinical-radiomics models were built, along with a nomogram. The AUC values for hematoma expansion prediction were as follows in the training set: NCCT model (0.758), clinical model (0.742), radiomics model (0.779), and combined model (0.872). In the validation set, the AUCs were: NCCT model (0.853), clinical model (0.754), radiomics model (0.778), and combined model (0.905). Calibration and decision curve analysis further confirmed the superior clinical utility of the combined model over the individual models. In conclusion, the combined NCCT-clinical-radiomics model significantly outperformed the individual models, leading to improved predictive accuracy, stability, and generalizability.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e00833"},"PeriodicalIF":3.2,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Approaches to Understand Movement as Medicine","authors":"Kieran F. Reid","doi":"10.1002/adbi.202400709","DOIUrl":"https://doi.org/10.1002/adbi.202400709","url":null,"abstract":"&lt;p&gt;This &lt;i&gt;Special Section&lt;/i&gt; of &lt;i&gt;Advanced Biology&lt;/i&gt; provides new insights, novel perspectives, and future directions to advance our understanding of “movement as medicine”. With a distinct translational science perspective, this section included studies ranging from molecular level transcriptome experiments in mice to late phase efficacy clinical trials of mind-body interventions. A unique combination of original investigations is presented that describes two preclinical studies of exercise training to induce neural regeneration and cardiac remodeling,&lt;sup&gt;[&lt;/sup&gt;&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt;&lt;sup&gt;]&lt;/sup&gt; an innovative characterization of the gut microbiome within elite athletes and sedentary controls,&lt;sup&gt;[&lt;/sup&gt;&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;&lt;sup&gt;]&lt;/sup&gt; studies on new approaches to further delineate anthropometric aspects of sarcopenia&lt;sup&gt;[&lt;/sup&gt;&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt;&lt;sup&gt;]&lt;/sup&gt; and sarcopenic obesity,&lt;sup&gt;[&lt;/sup&gt;&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt;&lt;sup&gt;]&lt;/sup&gt; a characterization of neurohemodynamic responses to acute aerobic exercise in pre-dementia older adults,&lt;sup&gt;[&lt;/sup&gt;&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt;&lt;sup&gt;]&lt;/sup&gt; the efficacy of a music-based mind-body program of Dalcroze Eurthymics for improving patient-important outcomes in older adults at high fall risk,&lt;sup&gt;[&lt;/sup&gt;&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt;&lt;sup&gt;]&lt;/sup&gt; and a comprehensive narrative review of physical, pharmacological, and multimodality therapeutic approaches to mitigate the impact of musculoskeletal diseases among individuals living with spinal cord injury (SCI).&lt;sup&gt;[&lt;/sup&gt;&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt;&lt;sup&gt;]&lt;/sup&gt;&lt;/p&gt;&lt;p&gt;Fang et al.&lt;sup&gt;[&lt;/sup&gt;&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;sup&gt;]&lt;/sup&gt; sought to examine the potential molecular mechanisms of exercise-induced axonal regeneration in a mouse model of optic nerve injury. Several weeks of exercise stimulation restored DNA methylation patterns and promoted retinal ganglion cell (RGC) axon regeneration via TET3 mediated epigenetic effects. The authors then further demonstrated in a series of elegant experiments that exercise training induced RGC axon regeneration, reestablished visual circuits, partially restored vision loss, and improved metabolic function in older mice. This elucidation of the mechanistic effects of exercise-induced regeneration of these functionally important CNS neurons may allow for the further development of novel regenerative approaches to mitigate the adverse effects of optic neuropathy in humans. In another preclinical study, Han et al.&lt;sup&gt;[&lt;/sup&gt;&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;&lt;sup&gt;]&lt;/sup&gt; examined whether a combination of endurance and resistance training could improve cardiac function. Compared to sedentary controls, aging mice underwent an 8-week intensive and progressive swimming or voluntary resistance running training regimen. This experimental approach revealed that both swimming and voluntary resistance running attenuated age-related cardiac hypertrophy and cellular senescence, cardiac metabolism, and oxidative stress, and they improved ","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"9 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adbi.202400709","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144308920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Masthead: (Adv. Biology 6/2025)","authors":"","doi":"10.1002/adbi.202570104","DOIUrl":"https://doi.org/10.1002/adbi.202570104","url":null,"abstract":"","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"9 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adbi.202570104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144308919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined Endurance and Resistance Exercise Mitigates Age-Associated Cardiac Dysfunction (Adv. Biology 6/2025)","authors":"Xiaowei Han,&nbsp;Muhammad Ashraf,&nbsp;Hong Shi,&nbsp;Augustine T. Nkembo,&nbsp;Srinivas M. Tipparaju,&nbsp;Wanling Xuan","doi":"10.1002/adbi.202570103","DOIUrl":"https://doi.org/10.1002/adbi.202570103","url":null,"abstract":"<p><b>Cardiac Aging</b></p><p>A combination of endurance and resistance exercises can mitigate age-related pathological changes in the heart in late life, such as cardiac remodeling and dysfunction. These beneficial effects on the heart are likely attributed to the activation of the anti-aging factor, Usf 2. More details can be found in article number 2400137 by Wanling Xuan and co-workers.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"9 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adbi.202570103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144308867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperoxia Induced Alteration of Chromatin Structure in Human Bone Marrow Derived Primary Mesenchymal Stromal Cells.","authors":"Lauren Monroe, Samantha Kaonis, Natalie Calahan, Neda Kabi, Soham Ghosh","doi":"10.1002/adbi.202400314","DOIUrl":"https://doi.org/10.1002/adbi.202400314","url":null,"abstract":"<p><p>In eukaryotic cell nuclei, chromatin exhibits a high degree of structural and functional dynamics. Recent findings suggest that chromatin has the ability to reorganize in response to changes within the cellular microenvironment. Such changes include oxidative stress found in hyperoxia. While hyperoxia is recognized for causing DNA damage and disrupting cellular functions, the effects it has on chromatin structure and the implications thereof remain poorly understood. In this work, an imaging-based technique is developed to visualize and characterize nanoscale chromatin remodeling under hyperoxia in mesenchymal stromal cells, created via hydrogen peroxide treatment. High spatiotemporal variability of remodeling in different chromatin domains is found. Chromatin remodeling is hindered by the GSK126-mediated inhibition of methyltransferase EZH2, which regulates the chromatin compaction. Independent assays such as ATAC seq further revealed that chromatin is compacted by hyperoxia, which is mitigated by GSK126 pretreatment. Epigenetic modifications and DNA damage under hyperoxia is investigated, which is also found to be affected by the pretreatment of GSK126. The techniques and discoveries provide mechanistic insights into chromatin remodeling, potentially paving the way for novel therapeutic strategies to combat genotoxic oxidative stress-commonly associated with degenerative diseases and aging-and to enhance cell-based therapies in regenerative medicine.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e00314"},"PeriodicalIF":3.2,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}