{"title":"Puerarin Ameliorates Premature Ovarian Failure by Activation of Mitochondrial Biogenesis, Dynamics, and Mitophagy Through Up-Regulation of SIRT1","authors":"Yuejuan Fang, Limei Huang, Fengyue Li, Xiuli Ding, Hongmei Zhou, Shun Xu","doi":"10.1002/adtp.202400310","DOIUrl":"10.1002/adtp.202400310","url":null,"abstract":"<p>Premature ovarian failure (POF) is characterized by ovarian atrophy and decreased fertility. Puerarin (Pue), an isoflavone compound, exerts protective effects on ovarian, however, with undefined mechanisms in POF. POF models were established by cyclophosphamide, and Pue and silent information regulator sirtuin 1 (SIRT1) inhibitor Selisistat (EX527) were used. Next, extracted primary rat ovarian granulosa cells (GCs) were treated with EX527 and autophagy activator rapamycin (RA). The data showed that in POF rats, Pue ameliorated estrous cycle, pathological damage, and senescence with higher ovarian index, anti-Müllerianhormone, estradiol, glutathione peroxidase, superoxide dismutase, mitochondrial DNA, and lower luteinizing hormone and follicle-stimulating hormone levels. In GCs, Pue increased cell viability, mitochondrial membrane potential, adenosine triphosphate levels, with decreased senescence and reactive oxygen species. Moreover, Pue induced mitophagy, enhanced peroxisome proliferators-activated receptor-γ coactivator-1alpha (PGC-1α), and reduced malondialdehyde, p16INK4a, p-adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK)/AMPK, mitochondrial transcription factor A, nuclear respiratory factor 1, dynamin-related protein 1, and mitochondrial fission 1 expression. Notably, the EX527 addition offset the above effects, while RA further reversed effects of EX527. In conclusion, Pue activated mitochondrial biogenesis, dynamics and mitophagy through up-regulation of SIRT1/PGC-1α pathway to ameliorate POF, providing a theoretical support for clinical application of Pue in POF.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944958","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}
Huiwen Pang, Wenxuan Yu, Youzhi Wu, Xuqiang Nie, Guojun Huang, Zhi Ping Xu, Chen Chen, Felicity Y. Han
{"title":"Enhanced Epithelial Cell Uptake of Glycol Chitosan-Coated PLGA Nanoparticles for Oral Drug Delivery","authors":"Huiwen Pang, Wenxuan Yu, Youzhi Wu, Xuqiang Nie, Guojun Huang, Zhi Ping Xu, Chen Chen, Felicity Y. Han","doi":"10.1002/adtp.202400547","DOIUrl":"10.1002/adtp.202400547","url":null,"abstract":"<p>It is reported that poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) coated with chitosan and its derivatives, such as glycol chitosan (GC), can enhance the targeted uptake of PLGA NPs by intestinal epithelial cells. However, the optimal amount of GC for coating and the specific mechanisms by which it facilitates PLGA endocytosis remain unclear. In this study, PLGA-NPs are prepared using either single- or double-emulsion methods and coated with varying amounts of GC. The results confirmed that GC-coated PLGA NPs are internalized via both clathrin-mediated and caveolae-mediated endocytosis, whereas uncoated NPs relied on only clathrin-mediated endocytosis in Caco-2 and HT-29 cells. The optimized GC-coated PLGA-NPs formulation is further modified by layering alginate to enhance the oral delivery of insulin. In subsequent in vivo studies, the GC and alginate-coated PLGA NPs demonstrated stability and prolonged efficacy, achieving approximately a 50% reduction in blood glucose levels at 6 h post-administration in streptozotocin-induced diabetic mice. These findings provide compelling evidence of the optimal coating amount and molecular mechanisms for GC in the PLGA oral platform, underscoring the feasibility and commercial potential of oral delivery platform based on the optimized GC- and alginate-coated PLGA NPs.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 6","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202400547","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309119","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}
Amin Ariaee, Hannah R. Wardill, Anthony Wignall, Aurelia S. Elz, Leah Wright, Clive Prestidge, Paul Joyce
{"title":"Therapeutic Potential of Inulin-Coated MCT Microcapsules in Modulating the Gut Microbiome for Effective Treatment of Diet-Induced Obesity (Adv. Therap. 3/2025)","authors":"Amin Ariaee, Hannah R. Wardill, Anthony Wignall, Aurelia S. Elz, Leah Wright, Clive Prestidge, Paul Joyce","doi":"10.1002/adtp.202570006","DOIUrl":"10.1002/adtp.202570006","url":null,"abstract":"<p>In article 2400305, Paul Joyce and co-workers present inulin-coated medium-chain triglyceride (InuMCT) microcapsules as a novel approach to treat diet-induced obesity in rats. InuMCT improves high-density lipoprotein, lowers blood glucose, reduces systemic inflammation, and supports beneficial gut bacteria, offering as a potential multifunctional therapy for metabolic diseases.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202570006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645928","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}
{"title":"Nanoparticles in Allergen-Delivery Systems for Allergen-Specific Immunotherapy (Adv. Therap. 3/2025)","authors":"Jiann Huey Lee, Rona Chandrawati, N. Alice Lee","doi":"10.1002/adtp.202570008","DOIUrl":"10.1002/adtp.202570008","url":null,"abstract":"<p>Allergen-specific immunotherapy shows great promise for treating pediatric allergies. The central carousel depicts various nanoparticles (outer layer) targeting different allergens (middle layer) for specific immunotherapies (center). The background highlights the uptake of nanoparticles (green) by antigen-presenting cells (red), illustrating the innovative approach. More details can be found in article 2400223 by N. Alice Lee and co-workers. Parts of the cover image were created with BioRender.com.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202570008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645784","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}
Sari Rasheed, Florian Umstätter, Eric Mühlberg, Barbro Beijer, Tobias Hertlein, Karel D. Klika, Christian Kleist, Julia Werner, Cornelius Domhan, Mara Bingel, Anna Müller, Marvin Rausch, Stefan Zimmermann, Knut Ohlsen, Uwe Haberkorn, Marcus Koch, Markus Bischoff, Tanja Schneider, Rolf Müller, Jennifer Herrmann, Walter Mier, Philipp Uhl
{"title":"Antibiotic–Polycationic Peptide Conjugation as an Effective Strategy to Overcome Daptomycin Resistance","authors":"Sari Rasheed, Florian Umstätter, Eric Mühlberg, Barbro Beijer, Tobias Hertlein, Karel D. Klika, Christian Kleist, Julia Werner, Cornelius Domhan, Mara Bingel, Anna Müller, Marvin Rausch, Stefan Zimmermann, Knut Ohlsen, Uwe Haberkorn, Marcus Koch, Markus Bischoff, Tanja Schneider, Rolf Müller, Jennifer Herrmann, Walter Mier, Philipp Uhl","doi":"10.1002/adtp.202400473","DOIUrl":"10.1002/adtp.202400473","url":null,"abstract":"<p>The benefit that antibiotics confer to the welfare of mankind is threatened by bacterial resistance. Resistance to daptomycin, a cyclic lipopeptide frequently used for the treatment of complicated bacteremia, is a prime example of this alarming situation. As the restricted number of antibacterial drug targets limits <i>de novo</i> development, chemical modification of existing compounds represents an alternative development option for future antimicrobials. This approach involves altering compounds to target bacteria through multiple mechanisms and/or to reinforce them against resistant strains. Herein, the conjugation of polycationic peptides to daptomycin enhances its effectiveness against a highly daptomycin-resistant laboratory strain of <i>Staphylococcus aureus</i> and clinical isolates of <i>Enterococcus faecium</i> with reduced daptomycin sensitivity. Notably, unlike daptomycin, the activity of these conjugates does not necessarily depend on the calcium concentration. In addition to regaining bacteriolytic activity, the findings indicate the acquisition of an additional or amended mode of action as evidenced by pore formation and the disruption of membrane potential. The combination of enhanced in vitro potency, in vivo activity, and tolerability highlights the potential of this drug modification strategy in combating multidrug-resistant bacteria.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202400473","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944969","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}
{"title":"On the Relentless Pursuit of an Oral Insulin Delivery System: How Far is Too Far?","authors":"Sourav Bhattacharjee","doi":"10.1002/adtp.202400566","DOIUrl":"10.1002/adtp.202400566","url":null,"abstract":"<p>As the scientific community celebrates the centenary year of insulin discovery, developing oral insulin delivery systems remains challenging, with disappointing progress. On the contrary, injectable formulations, despite initial setbacks due to poor patient compliance and issues with painful daily injections, have improved considerably—and currently remain the mainstay of insulin therapeutics. Advanced microneedle technology has enabled insulin delivery with minimal nociception in conjunction with automated, user-friendly delivery platforms. Furthermore, integrating modalities like insulin pumps delivering precise doses based on blood glucose monitoring has emerged. Conversely, oral insulin delivery continues to face arcane challenges, including the denaturation of insulin due to acidic gastric juice, a hostile gut mucus barrier that immobilizes and then removes particulate formulations, and a portal circulation that shunts the residue minuscule (nano)particulate dose from the bloodstream into the liver followed by macrophage activation and hepatobiliary elimination. Unless these barriers are negotiated, breaking the impasse in oral insulin delivery remains elusive. This perspective argues in favor of focusing solely on injectable insulin while deprioritizing, if not fully ceasing, further research toward developing oral insulin formulations to prevent wasting both taxpayers’ money and unethical consumption of animal lives.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 6","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202400566","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144308745","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}
Ruobing Bai, Gang Wang, Boru Hou, Dengfeng Wang, Ruihao Li, Zipeng Xu, Weibin Ma, Hongbin Liu
{"title":"Hydrogel Delivering All-Trans Retinoic Acid to Regulate Macrophage Polarization to Enhance Chemo-Immunotherapy for Gastric Cancer","authors":"Ruobing Bai, Gang Wang, Boru Hou, Dengfeng Wang, Ruihao Li, Zipeng Xu, Weibin Ma, Hongbin Liu","doi":"10.1002/adtp.202400024","DOIUrl":"10.1002/adtp.202400024","url":null,"abstract":"<p>As Gastric cancer is one of the most common gastrointestinal malignancies in China, with a 5-year relative survival rate of ≈40%. Therefore, the development of new strategies to treat gastric cancer becomes urgent. In recent years, an increasing number of studies have found that all-trans retinoic acid (Tre) can induce the polarization of M2 macrophages toward M1 in the tumor immune microenvironment (TIME), and therefore play a due role in this cancer treatment. This research proposes to load doxorubicin (DOX) and Tre in mesoporous silica, which is then loaded into sodium alginate slow-release Gel to obtain the final product (GEL-MSDT). Gel-MSDT sustained-release hydrogel can release DOX and Tre locally in tumor, kill tumor cells, induce tumor immunogenic death, regulate tumor-associated macrophage phenotype, and promote anti-tumor immune response. Gel-MSDT hydrogel can coordinate chemotherapy with immunotherapy, and delay release locally to play a lasting anti-tumor immune effect. The results of in vitro and in vivo experiments show that hydrogel can significantly inhibit tumor growth, providing an effective new strategy for the treatment of gastric cancer.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944884","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}
{"title":"Integrative Network Pharmacology and Bulk RNA-Seq Unveil Berberine's Modulation of Mitochondrial Function and Oxidative Stress via SOD2 in Experimental Models of Ovarian Cancer","authors":"Yujie Cheng, Bing Xiong, Jing Guo, Xiao Li, Lingwei Li, Jiajun Wang, Jiale Li, Siqi Liu, Hang Zhou, Lian Wang, Zhongping Cheng","doi":"10.1002/adtp.202400417","DOIUrl":"10.1002/adtp.202400417","url":null,"abstract":"<p>Ovarian cancer (OC) remains a formidable gynecological malignancy with limited therapeutic options and substantial side effects associated with conventional treatments. Berberine (BBR), a natural isoquinoline alkaloid, has shown promising anti-cancer properties; however, its mechanisms of action in OC are not fully elucidated. In this study, an integrative approach is employed that combines network pharmacology, molecular docking, molecular dynamics stability analysis and bulk RNA sequencing (bulk RNA-seq) to identify OC-related targets of BBR. In vivo and in vitro experiments demonstrate that BBR significantly inhibited tumor growth and metastasis in a mouse peritoneal metastasis model. Moreover, it is further confirmed that BBR modulates the OC microenvironment under high-lipid conditions by activating Superoxide Dismutase2 (SOD2), reducing lipid metabolism, and decreasing Reactive Oxygen Superspecies (ROS) levels.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944883","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}