{"title":"Mesenchymal stem cell-derived exosomal microRNA-367-3p mitigates lower limb ischemia/reperfusion injury in mouse skeletal muscle via EZH2 targeting.","authors":"Huanhuan Sun, Jueqiong Wang, Wei Bi, Feng Zhang, Kai Zhang, Xitao Tian, Xiang Gao, Yanrong Zhang","doi":"10.1093/jpp/rgae086","DOIUrl":"10.1093/jpp/rgae086","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the protective effect of bone marrow mesenchymal stem cell-derived exosomes (BMSCs-exo) against lower limb ischemia/reperfusion (I/R) injury-induced pyroptosis in skeletal muscle.</p><p><strong>Methods: </strong>A mouse model of lower limb I/R injury was utilized to assess the impact of BMSCs-exo, particularly when loaded with microRNA-367-3p (miR-367-3p), on pyroptosis. Histological examination, wet weight/dry weight ratio measurements, and luciferase assays were employed to elucidate the mechanisms involved.</p><p><strong>Key findings: </strong>BMSCs-exo effectively suppressed pyroptosis in injured skeletal muscle tissue. Loading BMSCs-exo with miR-367-3p enhanced this protective effect by downregulating key pyroptosis-related proteins. Luciferase assays identified enhancer of zeste homolog 2 (EZH2) as a direct target of miR-367-3p in BMSCs-exo.</p><p><strong>Conclusions: </strong>BMSCs-exo loaded with miR-367-3p safeguarded mouse skeletal muscle against pyroptosis-induced I/R injury by targeting EZH2. These findings offer valuable insights into potential therapeutic strategies for lower limb I/R injuries, emphasizing the therapeutic potential of BMSCs-exo in mitigating tissue damage caused by pyroptosis.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1634-1646"},"PeriodicalIF":2.8,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975976","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":"Production of mRNA lipid nanoparticles using advanced crossflow micromixing.","authors":"Muattaz Hussain, Burcu Binici, Liam O'Connor, Yvonne Perrie","doi":"10.1093/jpp/rgae122","DOIUrl":"10.1093/jpp/rgae122","url":null,"abstract":"<p><strong>Objectives: </strong>Lipid nanoparticles (LNPs) play a crucial role in RNA-based therapies, and their production is generally based on nanoprecipitation and coalescence of lipids around an RNA core. This study investigated crossflow micromixing to prepare LNPs across various mixing ratios and production speeds.</p><p><strong>Methods: </strong>A range of LNPs were prepared using crossflow micromixing across production speeds of 10-500 ml/min, and their physico-chemical characteristics (size, polydispersity index (PDI), zeta potential, and mRNA encapsulation), in vitro mRNA expression and in vitro efficacy (protein expression and antibody and cytokine responses).</p><p><strong>Key findings: </strong>Our results demonstrate the reproducible production of mRNA-LNPs with controlled critical quality attributes, including high mRNA encapsulation from the initial screening scale through to GMP-scale production, where the same mixing ratio can be adopted across all product speeds from 30 to 500 ml/min used.</p><p><strong>Conclusions: </strong>We confirm the applicability of stainless-steel crossflow membrane micromixing for the entire spectrum of mRNA-LNP production, ranging from initial discovery volumes to GMP-production scale.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1572-1583"},"PeriodicalIF":2.8,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468356","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":"Puerarin improves Dioscorea bulbifera L.-induced liver injury by regulating drug transporters and the Nrf2/NF-κB/Bcl-2 signaling pathway.","authors":"Xin Wang, Yuhan Zhang, Hongzhe Zhu, Leilei Shi, Yong Shi, Shanshan Cao, Jiping Liu, Yundong Xie","doi":"10.1093/jpp/rgae123","DOIUrl":"10.1093/jpp/rgae123","url":null,"abstract":"<p><strong>Purpose: </strong>Investigate the protective effect and mechanism of Puerarin (PU) against Dioscorea bulbifera L. (DB)-induced liver injury.</p><p><strong>Materials and methods: </strong>The protective effect of PU against DB-induced liver injury was evaluated by the present animal experiment, which assessed the pathological changes in the liver of mice and detected Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (AKP), as well as inflammation and oxidative stress-related indexes. Finally, the transcription and expression of related proteins were detected using western blot and quantitative reverse transcription (PCR) techniques.</p><p><strong>Results: </strong>PU significantly increased body weight, reduced liver index, and attenuated pathological changes in the liver compared to the DB group. It also decreased levels of AST, ALT, AKP, tumor necrosis factor-α, interleukin-1β, and malondialdehyde while increasing interleukin-10 levels and superoxide dismutase activity. Additionally, it upregulated inhibitor of NF-κB (IκB-α), B-cell lymphoma-2 (Bcl-2), Nuclear respiratory factor 2 (Nrf2), and Heme oxygenase 1 (HO-1) expression while down-regulating p-NF-κB p65 and bcl2-associated x (Bax) expression in the liver. Furthermore, PU upregulated protein and gene expression levels of Multidrug resistance-associated protein2, bile salt export pump, p-glycoprotein, and UDP-glucuronyltransferase 1A1 (UGT1A1) as well.</p><p><strong>Conclusion: </strong>PU mitigates DB-induced liver injury by regulating the expression of drug transporters and modulating the Nrf2/NF-κB/Bcl-2 signaling pathway.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1620-1633"},"PeriodicalIF":2.8,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391388","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":"Correction to: Current treatments for oropharyngeal squamous cell carcinoma and the move towards molecular therapy.","authors":"","doi":"10.1093/jpp/rgae139","DOIUrl":"10.1093/jpp/rgae139","url":null,"abstract":"","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1660"},"PeriodicalIF":2.8,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522221","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":"Current treatments for oropharyngeal squamous cell carcinoma and the move towards molecular therapy.","authors":"Mitra Elmi, Joshua H Dass, Crispin R Dass","doi":"10.1093/jpp/rgae107","DOIUrl":"10.1093/jpp/rgae107","url":null,"abstract":"<p><strong>Objectives: </strong>In this review, we discuss oropharyngeal squamous cell carcinoma (OPSCC) treatment options with a focus on the molecular mechanisms of OPSCC in head and neck squamous cell carcinoma (HNSCC) and head and neck cancers (HNCs). Treatment can be radical intent (aim for cure) or palliative intent (aim for disease control and symptom management). OPSCC is a prominent subset of HNSCCs in Australia and the Western World.</p><p><strong>Method: </strong>We looked at the current conventional treatment options with an overview of recent advances and future endeavours.</p><p><strong>Key findings: </strong>We identified that radiotherapy is the primary management for OPSCC in most countries, including the USA, UK, NZ, and Australia. In contrast, surgery is only considered for superficial OPSCC or neck surgery. If surgery is incomplete, then definitive management still requires radiotherapy.</p><p><strong>Conclusion: </strong>Molecular therapy is largely at the preclinical stage, with cetuximab, nivolumab, pembrolizumab, Lenvatinib, and bevacizumab being tested clinically currently.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1552-1562"},"PeriodicalIF":2.8,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975975","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":"Genistein and daidzein induce ferroptosis in MDA-MB-231 cells.","authors":"Ege Arzuk, Güliz Armağan","doi":"10.1093/jpp/rgae106","DOIUrl":"10.1093/jpp/rgae106","url":null,"abstract":"<p><strong>Objectives: </strong>In recent years, there has been a growing interest in targeting ferroptosis for the treatment and prevention of multiple cancers. This study aimed to assess the contribution of ferroptosis to the antiproliferative effects of genistein (GN) and daidzein (DZ) in breast cancer cell lines.</p><p><strong>Methods: </strong>MDA-MB-231 and MCF-7 cells were employed as an in vitro model. The antiproliferative effects of GN and DZ were determined by WST-1 assay in the presence of specific inhibitors of different cell death pathways. The mRNA expressions of Gpx4 and Fsp-1, the levels of lipid peroxidation, glutathione (GSH)/glutathione disulfide (GSSG) ratio, and intracellular iron ion content were assessed in GN- or DZ-treated cells.</p><p><strong>Results: </strong>GN and DZ were found to cause ferroptotic cell death in MDA-MB-231, as confirmed by the reversal of viability when cells were pretreated with ferrostatin-1. Furthermore, both phytochemicals induced biochemical markers of ferroptosis, including lipid peroxidation and iron ions levels, and decreased GSH/GSSG levels. The mRNA expression levels of the main anti-ferroptotic genes, Gpx4 and Fsp-1, were diminished by the treatment of both phytochemicals. Surprisingly, ferroptosis did not play a role in GN- or DZ-induced cell death in MCF-7 cells.</p><p><strong>Conclusion: </strong>Our findings highlight the potential of GN and DZ as ferroptosis inducers in triple-negative breast cancer cells.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1599-1608"},"PeriodicalIF":2.8,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154377","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}
Anfal F Bin Dayel, Nouf M Alrasheed, Asma S Alonazi, Maha A Alamin, Nawal M Al-Mutairi, Raghad A Alateeq
{"title":"Renoprotective effect of liraglutide on diabetic nephropathy by modulation of Krüppel-like transcription factor 5 expression in rats.","authors":"Anfal F Bin Dayel, Nouf M Alrasheed, Asma S Alonazi, Maha A Alamin, Nawal M Al-Mutairi, Raghad A Alateeq","doi":"10.1093/jpp/rgae127","DOIUrl":"10.1093/jpp/rgae127","url":null,"abstract":"<p><strong>Objectives: </strong>Diabetic nephropathy (DN) is a serious consequence of diabetes that can develop through the lysophosphatidic acid axis. The purpose of this study was to determine whether the antidiabetic drug liraglutide can slow the development of diabetic kidney damage by altering the lysophosphatidic acid axis via KLF5.</p><p><strong>Methods: </strong>Wistar albino rats were divided into nondiabetic and diabetic rats (resulting from an intraperitoneal streptozotocin dose of 30 mg/kg and a high-fat diet). These rats were further divided into four groups: nondiabetic control, liraglutide-treated nondiabetic, diabetic control, and liraglutide-treated diabetic. The nondiabetic and diabetic control groups received normal saline for 42 days, while the liraglutide-treated nondiabetic and diabetic groups received normal saline for 21 days, followed by a subcutaneous dose of liraglutide (200 μg/kg/day) for 21 days. Subsequently, serum levels of DN biomarkers were evaluated, and kidney tissues were histologically examined. The protein expression of PCNA, autotaxin, and KLF5 was detected.</p><p><strong>Key findings: </strong>Liraglutide treatment in diabetic rats decreased DN biomarkers, histological abnormalities in kidney tissues, and the protein expression of PCNA, autotaxin, and KLF5.</p><p><strong>Conclusion: </strong>Liraglutide can slow the progression of DN by modulating KLF5-related lysophosphatidic acid axis. Thus, liraglutide may be an effective treatment for preventing or mitigating diabetes-related kidney damage.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1563-1571"},"PeriodicalIF":2.8,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468371","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}
Sayed Haidar Abbas Raza, Ruimin Zhong, Xiangmei Li, Sameer D Pant, Xing Shen, Mona N BinMowyna, Lin Luo, Hongtao Lei
{"title":"Ganoderma lucidum triterpenoids investigating their role in medicinal applications and genomic protection.","authors":"Sayed Haidar Abbas Raza, Ruimin Zhong, Xiangmei Li, Sameer D Pant, Xing Shen, Mona N BinMowyna, Lin Luo, Hongtao Lei","doi":"10.1093/jpp/rgae133","DOIUrl":"10.1093/jpp/rgae133","url":null,"abstract":"<p><strong>Objectives: </strong>Ganoderma lucidum (GL) is a white rot fungus widely used for its pharmacological properties and health benefits. GL consists of several biological components, including polysaccharides, sterols, and triterpenoids. Triterpenoids are often found in GL in the form of lanostane-type triterpenoids with quadrilateral carbon structures.</p><p><strong>Key findings: </strong>The study revealed that triterpenoids have diverse biological properties and can be categorized based on their functional groups. Triterpenoids derived from GL have shown potential medicinal applications. They can disrupt the cell cycle by inhibiting β-catenin or protein kinase C activity, leading to anti-cancer, anti-inflammatory, and anti-diabetic effects. They can also reduce the production of inflammatory cytokines, thus mitigating inflammation. Additionally, triterpenoids have been found to enhance the immune system's defenses against various health conditions. They possess antioxidant, antiparasitic, anti-hyperlipidemic, and antimicrobial activities, making them suitable for pharmaceutical applications. Furthermore, triterpenoids are believed to afford radioprotection to DNA, protecting it from radiation damage.</p><p><strong>Summary: </strong>This review focuses on the types of triterpenoids isolated from GL, their synthesis pathways, and their chemical structures. Additionally, it highlights the pharmacological characteristics of triterpenoids derived from GL, emphasizing their significant role in various therapeutic applications and health benefits for both humans and animals.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1535-1551"},"PeriodicalIF":2.8,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502627","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":"In vitro and in vivo performance of amorphous solid dispersions of ursolic acid as a function of polymer type and excipient addition.","authors":"Tingting Zhao, Chenming Gu, Jianbo Qi, Jingwen Liu, Yajun Wang, Xiaojing Chen, Fujiang Guo, Yiming Li","doi":"10.1093/jpp/rgae125","DOIUrl":"10.1093/jpp/rgae125","url":null,"abstract":"<p><strong>Objectives: </strong>The objective of this research was to enhance the bioavailability of ursolic acid (UA) by preparing multielement amorphous solid dispersion (ASD) systems comprising excipients.</p><p><strong>Methods: </strong>The ASDs were prepared via the solvent evaporation method, characterized by a range of techniques, and investigated with respect to permeability of human colorectal adenocarcinoma cell line (Caco-2) cells monolayers and pharmacokinetics, with comparisons made to the physical mixture and the pure drug.</p><p><strong>Key findings: </strong>The (UA-choline)-Polyethylcaprolactam-polyvinyl acetate-polyethylene glycol grafted copolymer (Soluplus)-Vitamin E polyethylene glycol succinate (TPGS) ASD demonstrated superior dissolution properties compared to the corresponding binary solid dispersions and ternary solid dispersions (P< .05). The permeability studies of Caco-2 cell monolayers revealed that the ASD exhibited moderate permeability, with an efflux rate that was significantly lower than that of the UA raw material (P< .05). Pharmacokinetic studies in rats demonstrated that the oral bioavailability of the ASD was 19.0 times higher than that of UA (P< .01).</p><p><strong>Conclusions: </strong>The research indicated that the multielement ASD could be employed as an efficacious drug delivery system for UA. Furthermore, the Soluplus/TPGS/choline combination represents a promising candidate for the fabrication of ASDs that can load weakly acidic and poorly soluble drugs.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1584-1598"},"PeriodicalIF":2.8,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406533","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}
Min Ouyang, Jianhua Wu, Xizhuo Hu, Changfu Liu, Dan Zhou
{"title":"Decoding the power of saponins in ferroptosis regulation and disease intervention: a review.","authors":"Min Ouyang, Jianhua Wu, Xizhuo Hu, Changfu Liu, Dan Zhou","doi":"10.1093/jpp/rgae144","DOIUrl":"https://doi.org/10.1093/jpp/rgae144","url":null,"abstract":"<p><strong>Objectives: </strong>This review endeavors to elucidate the complex interplay underlying diseases associated with ferroptosis and to delineate the multifaceted mechanisms by which triterpenoid and steroidal saponins modulate this form of cell death.</p><p><strong>Methods: </strong>A meticulous examination of the literature was undertaken, drawing from an array of databases including Web of Science, PubMed, and Wiley Library, with a focus on the keywords \"ferroptosis,\" \"saponin,\" \"cancer,\" \"inflammation,\" \"natural products,\" and \"signaling pathways.\"</p><p><strong>Key findings: </strong>Ferroptosis represents a distinctive mode of cell death that holds considerable promise for the development of innovative therapeutic strategies targeting a wide range of diseases, especially cancer and inflammatory disorders. This review reveals the nuanced interactions between saponins and critical signaling pathways, including system Xc--GSH-GPX4, Nrf2, p53, and mTOR. These interactions highlight the dual capacity of saponins to modulate ferroptosis, thereby offering fresh perspectives for therapeutic intervention.</p><p><strong>Conclusions: </strong>The insights garnered from this review significantly advance our comprehension of the dynamic relationship between saponins and ferroptosis. By shedding light on these mechanisms, this work sets the stage for leveraging these insights in the creation of pioneering approaches to disease treatment, marking a significant stride in the evolution of therapeutic modalities.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823545","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}