Advanced Therapeutics最新文献_第10页

Eltrombopag Inhibited Liver Cancer by Enhancing SMYD4 Protein Degradationvia TRIP12 Ubiquitinase Eltrombopag通过TRIP12泛素酶促进SMYD4蛋白降解抑制肝癌

IF 2.6 4区医学

Advanced Therapeutics Pub Date : 2025-02-03 DOI: 10.1002/adtp.202400372

Jiale Li, Qiqiang Zhang, Chunyan Wang, Shupeng Liu

{"title":"Eltrombopag Inhibited Liver Cancer by Enhancing SMYD4 Protein Degradationvia TRIP12 Ubiquitinase","authors":"Jiale Li, Qiqiang Zhang, Chunyan Wang, Shupeng Liu","doi":"10.1002/adtp.202400372","DOIUrl":"10.1002/adtp.202400372","url":null,"abstract":"According to prior studies, SET and MYND domain-containing protein 4 (SMYD4) is involved in tumor progression and metastasis, representing a potential therapeutic target for tumors. However, no specific inhibitors or drugs targeting SMYD4 are currently available. In this study, molecular docking and molecular dynamics simulations were used to screen small molecule lead compounds binding to SMYD4 protein. CCK8 assay, colony formation assay, EdU assay were used to analyze the viability and proliferation of tumor cells. Flow cytometric analysis was used to evaluate cell apoptosis and cell cycle. Clorazepate, Ativan, Darifenacin and Eltrombopag were found to bind with SMYD4 with the highest probability and to meet the five principles of the drug class. Molecular dynamics simulations showed that Eltrombopag had the strongest binding capacity to SMYD4 protein. The functional analysis showed that Eltrombopag inhibited hepatocellular carcinoma cell proliferation and promoted apoptosis in vivo and in vitro at low density. Moreover, Eltrombopag enhanced ubiquitination of SMYD4 protein and promoted its degradation via thyroid hormone receptor interactor 12(TRIP12). These findings suggest that Eltrombopag is a potential inhibitor of SMYD4 protein, representing a novel leading compound for SMYD4 and applied for tumor treatment.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 2","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dermal Substitutes for Clinical Management of Severe Burn Injuries: Current and Future Perspectives 严重烧伤临床治疗的皮肤替代品：当前和未来的观点

IF 2.6 4区医学

Advanced Therapeutics Pub Date : 2025-01-23 DOI: 10.1002/adtp.202400455

Van Vo, Hanif Haidari, Allison J. Cowin, Marcus Wagstaff, Bronwyn Dearman, Zlatko Kopecki

{"title":"Dermal Substitutes for Clinical Management of Severe Burn Injuries: Current and Future Perspectives","authors":"Van Vo, Hanif Haidari, Allison J. Cowin, Marcus Wagstaff, Bronwyn Dearman, Zlatko Kopecki","doi":"10.1002/adtp.202400455","DOIUrl":"10.1002/adtp.202400455","url":null,"abstract":"Despite significant advances in recent decades, severe burns remain a formidable challenge, with high morbidity and mortality rates. The immunocompromised state following severe burn injuries, compounded by the loss of the protective skin barrier, increases the risk of bacterial colonization and invasion. Without appropriate management, infections in burn patients can progress to sepsis, a life-threatening complication. Current burn care often fails to achieve optimal tissue regeneration and infection prevention, necessitating a combination of different approaches. Developing innovative and safer strategies to mitigate burn infections is essential for improving patient outcomes. This review provides updated insights into various biomaterials tailored for managing infections in severe burns, offering comprehensive insights and a summary of emerging technologies for potential clinical application. Additionally, an in-depth discussion on current research and clinical areas that warrant further investigation is presented. Potential avenues for next-generation dermal substitutes aimed at improving regeneration and preventing burn wound infections are then explored.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202400455","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bee Better: The Role of Honey in Modern Wound Care 蜜蜂更好：蜂蜜在现代伤口护理中的作用

IF 2.6 4区医学

Advanced Therapeutics Pub Date : 2025-01-23 DOI: 10.1002/adtp.202400502

Léo-Paul Tricou, Natalie Guirguis, Sarah Djebbar, Benjamin R. Freedman, Simon Matoori

引用次数: 0

Targeting VEGF-A in an Immunocompetent Orthotopic Mouse Model of Mesenchymal Glioblastoma Improves Antitumorigenicity and Decreases Proinflammatory Response in Normal Brain Tissue after Fractionated Radiotherapy 靶向VEGF-A的免疫功能小鼠间充质胶质母细胞瘤模型可提高正常脑组织分步放疗后的抗肿瘤性并降低促炎反应

IF 2.6 4区医学

Advanced Therapeutics Pub Date : 2025-01-23 DOI: 10.1002/adtp.202400374

Alexander Edward Nieto, Daniel Felix Fleischmann, Kristian Unger, Valerie Albrecht, Jessica Maas, Horst Zitzelsberger, Claus Belka, Martin Proescholdt, Kirsten Lauber, Maximilian Niyazi, Michael Orth

{"title":"Targeting VEGF-A in an Immunocompetent Orthotopic Mouse Model of Mesenchymal Glioblastoma Improves Antitumorigenicity and Decreases Proinflammatory Response in Normal Brain Tissue after Fractionated Radiotherapy","authors":"Alexander Edward Nieto, Daniel Felix Fleischmann, Kristian Unger, Valerie Albrecht, Jessica Maas, Horst Zitzelsberger, Claus Belka, Martin Proescholdt, Kirsten Lauber, Maximilian Niyazi, Michael Orth","doi":"10.1002/adtp.202400374","DOIUrl":"10.1002/adtp.202400374","url":null,"abstract":"Glioblastoma is the most aggressive primary brain tumor characterized by a dismal prognosis and a profound therapy resistance that is most evident for the mesenchymal molecular subtype of glioblastoma. Targeting vascular endothelial growth factor (VEGF)-A by the monoclonal antibody bevacizumab, despite failing to improve survival in randomized trials, yields relevant benefits in glioblastoma patients such as reduction of radionecrosis, an adverse event associated with radiotherapy. This demands for continued research to identify optimal combinations of anti-VEGF-A and standard therapies for glioblastoma treatment. We show here that blocking VEGF-A in an immune competent orthotopic glioblastoma mouse model resembling the adverse mesenchymal molecular subtype increases the tumoricidal effect of computed tomography (CT)-based fractionated radiotherapy and also rectifies irradiation-induced expression of genes with known association to mesenchymal subtype enrichment as revealed by microarray-based transcriptome analyses of explanted tumors. VEGF-A blockade also decreases the expression of myeloid-cell-related gene patterns in irradiated tumors and lowers inflammatory response in normal brain tissue after tumor irradiation. Hence, these data both provide a hint how blockade of VEGF-A increases the effect of radiotherapy in mesenchymal glioblastoma and a mechanistic base for clinical observations reporting reduced incidences of radionecrosis in glioblastoma patients treated with radiotherapy upon concurrent administration of bevacizumab.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 2","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202400374","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lipopeptide 01 from Staphylococcus Epidermidis Resists Pathogenic Bacteria and Promotes Bone Healing in Implant-Associated Infections 表皮葡萄球菌脂肽01抵抗病原菌并促进种植体相关感染的骨愈合

IF 2.6 4区医学

Advanced Therapeutics Pub Date : 2025-01-19 DOI: 10.1002/adtp.202400477

Shengjie Wang, Wei Liu, Chao Yang, Changwei Li, Xianlong Zhang

{"title":"Lipopeptide 01 from Staphylococcus Epidermidis Resists Pathogenic Bacteria and Promotes Bone Healing in Implant-Associated Infections","authors":"Shengjie Wang, Wei Liu, Chao Yang, Changwei Li, Xianlong Zhang","doi":"10.1002/adtp.202400477","DOIUrl":"10.1002/adtp.202400477","url":null,"abstract":"Implant-associated infections (IAI) present a significant clinical challenge. Effective prevention of and recovery from IAI is complex, involving antibacterial treatment and the promotion of bone integration. However, the current artificial implants used in clinics often lack effective antibacterial properties and have limited functionality. In this study, Lipopeptide 01 (LP01), a lipopeptide derived from the skin commensal Staphylococcus epidermidis is successfully immobilized, onto the porous surface of sulfonated Poly (ether-ether-ketone) (SPEEK) to create a novel artificial implant, LP01-PS. Both in vivo and in vitro experiments demonstrates that LP01-PS displays favorable material properties, biocompatibility, outstanding antibacterial characteristics, and the ability to promote bone formation. Mechanistically, LP01-PS enhances antibacterial activities by triggering TLR2/P65 signaling, upregulating the expression of LL37 and β-defensins in macrophages. Furthermore, it can boost the osteogenic differentiation capability of bone marrow mesenchymal stem cells (BMSCs) through the β-catenin signaling pathway, thereby facilitating bone formation. The discovery of LP01-PS with dual antibacterial and osteogenic effects, coupled with insights into its mode of action, suggests that LP01-PS can serve as a promising implant material to enhance the success rates of total joint replacement surgeries, mitigate the risks of infection and prosthetic loosening, and foster the repair and regeneration of bone tissue.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Disease-Adaptive Drug Delivery to the Inflamed Intestinal Mucosa Using Poly(Lactic-Co-Glycolic Acid)-cyclodextrin Hybrid Nanocarriers 利用聚（乳酸-共聚甘醇酸）-环糊精混合纳米载体向炎症肠黏膜进行疾病适应性给药

IF 2.6 4区医学

Advanced Therapeutics Pub Date : 2025-01-19 DOI: 10.1002/adtp.202400368

Jonas Schreiner, Felix E. B. Brettner, Sebastian Steigert, Annika Haessler, Raf Mols, Stefanie Gier, Nathalie Jung, Sarah Vogel-Kindgen, Susanne Muschert, Patrick Augustijns, Maike Windbergs

{"title":"Disease-Adaptive Drug Delivery to the Inflamed Intestinal Mucosa Using Poly(Lactic-Co-Glycolic Acid)-cyclodextrin Hybrid Nanocarriers","authors":"Jonas Schreiner, Felix E. B. Brettner, Sebastian Steigert, Annika Haessler, Raf Mols, Stefanie Gier, Nathalie Jung, Sarah Vogel-Kindgen, Susanne Muschert, Patrick Augustijns, Maike Windbergs","doi":"10.1002/adtp.202400368","DOIUrl":"10.1002/adtp.202400368","url":null,"abstract":"Fluctuating severity of symptoms is a common hallmark of many inflammatory disorders, including inflammatory bowel disease (IBD). Addressing the pH changes during active and resting phases in IBD-affected tissue, a disease-adaptive nanocarrier system is designed for oral administration, enabling pH-dependent local drug release. The hybrid carrier combines poly(lactic-co-glycolic acid) and an amphiphilic cyclodextrin derivative, with physicochemical properties and drug release kinetics controlled by adjusting polymer ratios. The systems exhibited baseline drug release at pH 5 with increased rates at pH 2, which is characteristic of actively inflamed IBD tissue. Assessing the impact of biomolecule adhesion, biocorona formation was studied using ex vivo human intestinal fluids. Corona composition highly depended on the patient's prandial state and the nanocarrier matrix, with proteins predominating in the fasted state and lipids in the fed state. Notably, differences in the attachment of proteins and free fatty acids are detected in the latter. Transport studies using human in vitro models of the inflamed intestine revealed mucosal accumulation, facilitating localized drug delivery and effectively reducing cytokine levels to basal concentrations. This hybrid system highlights the potential of disease-adaptive drug release for inflammatory disease treatment and underscores the impact of biocorona formation on therapeutic performance in the gastrointestinal tract.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 2","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202400368","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pathophysiology of IBD as a Key Strategy for Polymeric Nanoparticle Development IBD的病理生理是聚合物纳米颗粒开发的关键策略

IF 2.6 4区医学

Advanced Therapeutics Pub Date : 2025-01-19 DOI: 10.1002/adtp.202400439

Elena Gardey, Johannes C. Brendel, Andreas Stallmach

{"title":"Pathophysiology of IBD as a Key Strategy for Polymeric Nanoparticle Development","authors":"Elena Gardey, Johannes C. Brendel, Andreas Stallmach","doi":"10.1002/adtp.202400439","DOIUrl":"10.1002/adtp.202400439","url":null,"abstract":"Inflammatory bowel disease (IBD) is a complex chronic inflammatory disorder of the gastrointestinal (GI) tract with an uncertain etiology. Currently, IBD therapy relies on the induction of clinical remission followed by maintenance therapy using anti-inflammatory drugs and immunosuppressants; however, a definite cure of the disease is still out of scope. Established approaches are characterized by adverse drug-related side effects that can even be potentially life-threatening. In contrast, increased interest and remarkable scientific progress in targeted drug delivery systems offer a promising approach to reduce systemic adverse events, delivering the therapeutic substances only to inflamed tissue. All alteration in gastrointestinal barrier integrity, especially a disturbed epithelial barrier, a unique pattern of the receptors on cell surface and/or an oxidative stress milieu in inflamed areas can be used as effective approaches for targeted and controlled drug delivery. Hence, this review focuses on the pathophysiology of the inflamed GI tract as a potential strategy for targeted polymeric nanoparticles for IBD treatment. Interdisciplinary efforts between the polymeric chemistry and gastroenterology/immunology promise to create novel synergies that improve the development of effective nanoparticle systems with significant clinical impact. In this regard, the current challenges in the clinical translation of promising nanomedicine are also discussed.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202400439","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Full Disappearance of PC3-Luc Prostate Tumors Mediated by Hyperthermia Under Low Intensity Ultrasound Application in the Presence of Magnetosomes 在磁小体存在的情况下应用低强度超声波，通过热疗促使 PC3-Luc 前列腺肿瘤完全消失

IF 2.6 4区医学

Advanced Therapeutics Pub Date : 2025-01-19 DOI: 10.1002/adtp.202400281

Cynthia El Hedjaj, Eric Barret, Imène Chebbi, Raphaël Le Fèvre, Caroline Maake, Franco Guscetti, François Guyot, Jean-Francois Aubry, Olivier Seksek, Edouard Alphandéry

{"title":"Full Disappearance of PC3-Luc Prostate Tumors Mediated by Hyperthermia Under Low Intensity Ultrasound Application in the Presence of Magnetosomes","authors":"Cynthia El Hedjaj, Eric Barret, Imène Chebbi, Raphaël Le Fèvre, Caroline Maake, Franco Guscetti, François Guyot, Jean-Francois Aubry, Olivier Seksek, Edouard Alphandéry","doi":"10.1002/adtp.202400281","DOIUrl":"10.1002/adtp.202400281","url":null,"abstract":"Iron oxide nanoparticles have been proposed for magnetic hyperthermia treatment of tumors. However, efficacy depends on the injection of large amounts of such nanoparticles and the equipment is costly. Here, a new thermal cancer treatment is described, in which a tumor containing a low concentration of nonpyrogenic pure iron oxide nanominerals coated with carboxy-methyl-dextran (M-CMD), corresponding to modified magnetosomes, are exposed to ultrasound. Heating PC3 prostate carcinoma cells between 43 and 46°C using ultrasound in the presence of M-CMD resulted in significant necrotic cell death. Furthermore, deposition of M-CMD containing 3 µg of iron per mm3 of tumor in subcutaneous xenografts of PC3-Luc tumors of 150 mm3 followed by 6 to 10 sessions of ultrasound application (1 W cm−2, 1 MHz) of 10 min each led to a tumor temperature of 43–46°C per session and to total tumor disappearance without regrowth over 6 months following treatment start. Sequential histological analyses of the tumor tissues revealed partial tumor occupation by M-CMD and an increase in cell death over time. Neither lesions, nor magnetosome accumulation were found in microscopic sections of various internal organs collected from treated mice euthanized 6 months after the beginning of the treatment, indicating that M-CMD may not lead to long-term side effects.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 2","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202400281","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Controlled Drug Release Systems for Cerebrovascular Diseases (Adv. Therap. 1/2025) 脑血管疾病药物控释系统（Adv. Therap. 1/2025）

IF 2.6 4区医学

Advanced Therapeutics Pub Date : 2025-01-13 DOI: 10.1002/adtp.202570001

Celia Martín-Morales, Sofia Caspani, Manuel Desco, Célia Tavares de Sousa, María Victoria Gómez-Gaviro

引用次数: 0

Hybrid Nanoparticles Dual-Loaded With Curcumin and Benzydamine Hydrochloride for the Treatment of Vulvovaginal Candidiasis: From Development to Biological Application In Vitro and In Vivo (Adv. Therap. 1/2025) 姜黄素和盐酸苄胺复合纳米颗粒治疗外阴阴道念珠菌病：从发展到体外和体内生物学应用（ad . Therap. 1/2025）

IF 2.6 4区医学

Advanced Therapeutics Pub Date : 2025-01-13 DOI: 10.1002/adtp.202570003

Gabriela C. Carvalho, Maria Nolasco Viseu Domingues, Gabriel Davi Marena, Ermei Mäkilä, Jiachen Li, Gésinda Geertsema-Doornbusch, Cleverton Roberto de Andrade, Marc C. A. Stuart, Mohammad-Ali Shahbazi, Ione Corrêa, Brandon W. Peterson, Jarno Salonen, Helena F. Florindo, Taís Maria Bauab, Marlus Chorilli, Hélder A. Santos

引用次数: 0