Journal of Pharmacy and Pharmacology最新文献_第5页

Serum autotaxin level: a promising diagnostic biomarker in differentiating Graves' disease and thyroiditis. 血清自体表皮生长因子水平：区分巴塞杜氏病和甲状腺炎的有望诊断生物标志物

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2025-01-06 DOI: 10.1093/jpp/rgae073

Angel George, Anns Mariya, Manu Eappen, Marimuthu Karthikeyan, Ravindranath Sreenath

{"title":"Serum autotaxin level: a promising diagnostic biomarker in differentiating Graves' disease and thyroiditis.","authors":"Angel George, Anns Mariya, Manu Eappen, Marimuthu Karthikeyan, Ravindranath Sreenath","doi":"10.1093/jpp/rgae073","DOIUrl":"10.1093/jpp/rgae073","url":null,"abstract":"Background: Recent studies have suggested that serum autotaxin (ATX) may be a promising diagnostic biomarker in differentiating between Graves' disease (GD) and thyroiditis, as well as serving as a monitoring biomarker for GD. This study will evaluate the use of serum ATX as a diagnostic biomarker in these conditions.Methods: In this prospective interventional study, blood samples were collected from the patients who met both inclusion and exclusion criteria, and serum ATX levels were measured by using the MyBioSource human Autotaxin ELISA kit.Results: A total of 32 patients were enrolled, of which 18.8% were newly diagnosed with GD, 21.9% were thyroiditis, and 59.3% were on treatment for GD. Serum autotaxin antigen was significantly higher in GD patients than in thyroiditis (603.3217 ± 444.24 v/s 214.74 ± 55.91, P = <.005). Serum ATX measurement successfully discriminated GD patients from thyroiditis (AUC = 0.952, 95%CI: 0.00-1.00) with an optimal cutoff value of ≥257.20 ng/L (sensitivity = 100 and specificity = 81.71). Monitoring the efficacy of serum ATX was analyzed and showed a significant difference.Conclusion: The serum ATX was higher in subjects with GD as compared to thyroiditis, and ATX levels were found to be decreased during the treatment period. In conclusion, serum ATX can be used as a diagnostic and monitoring biomarker in GD.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"56-63"},"PeriodicalIF":2.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723805","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

Super-enhancer-driven ameboidal-type cell migration-related MMP14 expression in tongue squamous cell carcinoma switched by BATF and ATF3. 舌鳞状细胞癌中由BATF和ATF3切换的超级增强子驱动的meboidal型细胞迁移相关的MMP14表达。

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2025-01-06 DOI: 10.1093/jpp/rgae063

Zhimin Shi, Rui Wang, Jie Huang, Qian Qian, Menglin Hu, Hengguo Zhang, Linfei Feng, Hao Gu, Yuanyin Wang

{"title":"Super-enhancer-driven ameboidal-type cell migration-related MMP14 expression in tongue squamous cell carcinoma switched by BATF and ATF3.","authors":"Zhimin Shi, Rui Wang, Jie Huang, Qian Qian, Menglin Hu, Hengguo Zhang, Linfei Feng, Hao Gu, Yuanyin Wang","doi":"10.1093/jpp/rgae063","DOIUrl":"10.1093/jpp/rgae063","url":null,"abstract":"Background: Tongue squamous cell carcinoma (TSCC) exhibits an aggressive biological behavior of lymph node and distant metastasis, which contributes to poorer prognosis and results in tongue function loss or death. In addition to known regulators and pathways of cell migration in TSCC, it is important to uncover pivotal switches governing tumor metastasis.Methods: Cancer cell migration-associated transcriptional and epigenetic characteristics were profiled in TSCC, and the specific super-enhancers (SEs) were identified. Molecular function and mechanism studies were used to investigate the pivotal switches in TSCC metastasis.Results: Ameboidal-type cell migration-related genes accompanied by transcriptional and epigenetic activity were enriched in TSCC. Meanwhile, the higher-ranked SE-related genes showed significant differences between 43 paired tumor and normal samples from the TCGA TSCC cohort. In addition, key motifs were detected in SE regions, and transcription factor-related expression levels were significantly associated with TSCC survival status. Notably, BATF and ATF3 regulated the expression of ameboidal-type cell migration-related MMP14 by switching the interaction with the SE region.Conclusion: SEs and related key motifs transcriptional regulate tumor metastasis-associated MMP14 and might be potential therapeutic targets for TSCC.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"64-75"},"PeriodicalIF":2.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248278","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

Deciphering farnesol's anti-arthritic and immunomodulatory potential by targeting multiple pathways: a combination of network pharmacology guided exploration and experimental verification. 通过靶向多种途径破解法尼醇的抗关节炎和免疫调节潜力：网络药理学指导下的探索与实验验证相结合。

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2025-01-06 DOI: 10.1093/jpp/rgae126

Shaimaa R Ahmed, Ambreen Malik Uttra, Muhammad Usman, Sumera Qasim, Shah Jahan, Muhammad Roman, Hanan Khojah, Omnia Hendawy, Eman K Rashwan

{"title":"Deciphering farnesol's anti-arthritic and immunomodulatory potential by targeting multiple pathways: a combination of network pharmacology guided exploration and experimental verification.","authors":"Shaimaa R Ahmed, Ambreen Malik Uttra, Muhammad Usman, Sumera Qasim, Shah Jahan, Muhammad Roman, Hanan Khojah, Omnia Hendawy, Eman K Rashwan","doi":"10.1093/jpp/rgae126","DOIUrl":"10.1093/jpp/rgae126","url":null,"abstract":"Objective: Farnesol (FAR), a sesquiterpene alcohol, has documented FAR's anti-inflammatory and antioxidant activities. Current study was undertaken to assess the efficacy and mechanism of FAR in arthritis by employing network pharmacology and experimental models.Methods: Two experimental models comprising formaldehyde- and complete Freund's adjuvant (CFA)-induced arthritis evaluated the efficacy of FAR in treating arthritis. Various parameters were assessed. Then, a network pharmacology approach was applied to gain further insight into the potential mechanism and signaling pathways.Key findings: FAR significantly reduced paw volume and the arthritic score and improved the hematological and biochemical changes. Radiographic and histological examination showed the anti-arthritic efficacy of FAR, which was associated with down-regulation of pro-inflammatory mediators and upregulation of anti-inflammatory mediators. Network pharmacology analysis revealed that FAR may exert its anti-arthritic effects by targeting specific genes associated with arthritis. Pathway analysis revealed the involvement of three key signaling pathways (IL-17 signaling, TNF signaling, and toll-like receptor signaling) in the development and progression of arthritis.Conclusions: The results pointed out the protective attributes of farnesol against formaldehyde and CFA-induced arthritis via modulation of multiple targets. This study provides a valuable reference for the development of a new treatment or complementary therapy for arthritis.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"127-141"},"PeriodicalIF":2.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391387","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

Co-administration of Ceratonia siliqua extract nanoparticles promotes the oral bioavailability and neurotherapeutic efficacy of donepezil in a dementia model. 在痴呆症模型中，同时服用 Ceratonia siliqua 提取物纳米颗粒可提高多奈哌齐的口服生物利用度和神经治疗效果。

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2025-01-06 DOI: 10.1093/jpp/rgae094

Sylvia E Shaker, Dalia B Fayed, Heba Shawky, Ebtehal K Farrag

{"title":"Co-administration of Ceratonia siliqua extract nanoparticles promotes the oral bioavailability and neurotherapeutic efficacy of donepezil in a dementia model.","authors":"Sylvia E Shaker, Dalia B Fayed, Heba Shawky, Ebtehal K Farrag","doi":"10.1093/jpp/rgae094","DOIUrl":"10.1093/jpp/rgae094","url":null,"abstract":"Background: This study aimed to assess the herb-drug interactions between crude/silver nanoparticle (SNP)-loaded carob extract (Car, NCar, respectively) and donepezil-HCl (DPZ) and their impact on neurotherapeutic outcomes in a dementia model.Methods: Carob pods were subjected to ethanol extraction, and their phytoconstituents were chromatographically analysed. SNP-loaded extract was synthesized and characterized, and dementia-like symptoms were induced in Wistar rats by repeated dosing with 175 mg/kg AlCl3 for 60 days, after which the animals were treated with Car, NCar, DPZ, and combinations of Car/NCar-DPZ for 30 days. The effect of carob formulations on DPZ bioavailability was in-silico profiled and the herb-drug interactions were mathematically assessed as combination indices.Results: Different formulations significantly improved cognitive/spatial memory functions, restored dysregulated brain redox and cholinergic functions, and markedly inhibited cholinesterase, as reflected by the reduction/absence of amyloid plaques and neurofibrillary tangles. In silico profiling of the major phytoconstituents revealed their non-P-glycoprotein substrate nature and CYP3A4, 2C19, and 2C9 inhibition, which might have improved the oral bioavailability of DPZ. The combination index calculations revealed strong synergy between DPZ and both carob formulations, with the strongest effect exhibited by the DPZ/NCar combination.Conclusion: The co-administration of carob extract/SNPs represents a promising approach for enhancing the neurotherapeutic efficacy of DPZ.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"153-169"},"PeriodicalIF":2.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759411","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

Exploring the mechanism of pachymic acid intervention in myocardial ischemia based on network pharmacology and experimental validation. 基于网络药理学和实验验证探讨厚青酸干预心肌缺血的机制。

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2025-01-04 DOI: 10.1093/jpp/rgae153

Nengpin Yin, Xuan Zhao, Jin Yang, Zongjun Liu

{"title":"Exploring the mechanism of pachymic acid intervention in myocardial ischemia based on network pharmacology and experimental validation.","authors":"Nengpin Yin, Xuan Zhao, Jin Yang, Zongjun Liu","doi":"10.1093/jpp/rgae153","DOIUrl":"https://doi.org/10.1093/jpp/rgae153","url":null,"abstract":"Objectives: To deeply explore the mechanism of pachymic acid (PA) intervention in myocardial ischemia, providing new ideas and methods for the treatment of myocardial ischemia.Methods: Predict the targets of PA for improving myocardial ischemia, and conduct functional enrichment analysis using databases, such as Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Reactome. To verify these findings, PPI network topology analysis and molecular docking were used to screen key targets and main mechanisms of action and further validated through in vitro experiments on the H9C2 cell line.Key findings: PA can significantly alleviate myocardial damage caused by hypoxia/reoxygenation, effectively reversing the abnormalities of oxidative stress indicators such as LDH, MDA, SOD, and ROS. PA may exert its effects through 39 targets, particularly by regulating the downregulation of autophagy-related proteins LC3-II and Beclin-1 expression via MTOR, thereby inhibiting excessive autophagy in cardiomyocytes.Conclusions: PA protects myocardial cells during myocardial ischemia through various pathways, particularly by regulating mTOR to inhibit excessive autophagy.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932010","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

Piperlongumine inhibits glioblastoma proliferation by inducing ferroptosis. 胡椒明通过诱导铁下垂抑制胶质母细胞瘤增殖。

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2024-12-18 DOI: 10.1093/jpp/rgae148

Jianting Qiu, Fangzhou Guo, Ji Shi, Tangjun Guo, Haozhe Piao

{"title":"Piperlongumine inhibits glioblastoma proliferation by inducing ferroptosis.","authors":"Jianting Qiu, Fangzhou Guo, Ji Shi, Tangjun Guo, Haozhe Piao","doi":"10.1093/jpp/rgae148","DOIUrl":"https://doi.org/10.1093/jpp/rgae148","url":null,"abstract":"Objectives: This study aimed to investigate the effects of Piperlongumine on Glioblastoma multiforme.Methods: The effects of Piperlongumine on the viability and proliferation of glioma cells LN229 and A172 were measured. Changes in mitochondrial structure were observed. Cell proliferative capacity was assessed using immunofluorescence. The levels of glutathione, malondialdehyde, 4-hydroxynonenal, and intracellular reactive oxygen species were detected. The levels of ferroptosis-related proteins were detected. A plasmid transfection was performed to overexpress the nuclear factor erythroid 2-related factor 2 gene; a subcutaneous tumor model was established in nude mice to observe the in vivo inhibitory effects of Piperlongumine on Glioblastoma multiforme and the recovery effect of Fer-1. The expression levels of ferroptosis-related proteins were detected using immunohistochemistry.Key findings: Piperlongumine inhibited the viability of glioma cells, as well as their proliferation. The ferroptosis inhibitors were able to restore the inhibitory effect of Piperlongumine on glioma cell proliferation. Forced overexpression of nuclear factor erythroid 2-related factor 2 partially reversed Piperlongumine-induced ferroptosis; Piperlongumine exhibited a significant inhibitory effect on Glioblastoma multiforme cells in vivo, which could be restored by Fer-1.Conclusions: Piperlongumine inhibits Glioblastoma multiforme proliferation by inducing ferroptosis in vitro and vivo model.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846863","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

Exploring the molecular mechanism of Taohong Siwu decoction in the treatment of non-small-cell lung cancer based on network pharmacology and molecular docking. 基于网络药理学和分子对接的桃红四物汤治疗非小细胞肺癌的分子机制探索

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2024-12-16 DOI: 10.1093/jpp/rgae141

Yuan Qin, Jia-Ning Lian, Xin Chen, Feng-Yu Huang, Hai-Wen Chen, Tai-Wei Dong, Zuo-Lin Jin

{"title":"Exploring the molecular mechanism of Taohong Siwu decoction in the treatment of non-small-cell lung cancer based on network pharmacology and molecular docking.","authors":"Yuan Qin, Jia-Ning Lian, Xin Chen, Feng-Yu Huang, Hai-Wen Chen, Tai-Wei Dong, Zuo-Lin Jin","doi":"10.1093/jpp/rgae141","DOIUrl":"https://doi.org/10.1093/jpp/rgae141","url":null,"abstract":"Objective: This study aimed to explore the mechanism of Taohong Siwu decoction (THSWD) in the treatment of non-small-cell lung cancer (NSCLC) by using comprehensive analysis.Methods: The active components and relevant targets of THSWD were analyzed by network analysis to construct the active component-target-disease network diagram. Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted on the core targets by the Metascape database. Molecular docking verification was used for molecular visualization.Key findings: A total of 69 active compounds and 114 targets were filtered in lung cancer treatment with THSWD. KEGG analysis suggested that tumor necrosis factor (TNF) signaling pathway, and apoptosis pathway played critical roles. The results of molecular docking showed that populoside_qt with IL-6, baicalein with epidermal growth factor receptor (EGFR), and luteolin with MAPK8 had the strongest binding ability. Moreover, experiment validation revealed that THSWD regulated the expression of IL-6, AKT, Cyclin D1, E-cadherin, and LC3A/B, thereby inhibiting the proliferation and migration ability, promoting apoptosis, and blocking the cell cycle of NSCLC cells.Conclusions: The potential targets and molecular mechanisms of THSWD in the treatment of NSCLC were preliminarily revealed by a comprehensive analysis in this study, which will provide new ideas and methods for the study of the mechanism of traditional Chinese medicine in treating lung cancer.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836980","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

Croton grewioides essential oil and anethole reduce oxidative stress and improve growth of bovine primordial follicles during culture of ovarian tissue. 巴豆精油和茴香醚在卵巢组织培养过程中可降低氧化应激，改善牛原始卵泡的生长。

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2024-12-02 DOI: 10.1093/jpp/rgae093

Felipe F da Silva, Francisco das Chagas Costa, Venância A N Azevedo, Ernando I T de Assis, Geovany A Gomes, Valdevane R Araújo, Selene M de Morais, Tigressa H S Rodrigues, José R V Silva

{"title":"Croton grewioides essential oil and anethole reduce oxidative stress and improve growth of bovine primordial follicles during culture of ovarian tissue.","authors":"Felipe F da Silva, Francisco das Chagas Costa, Venância A N Azevedo, Ernando I T de Assis, Geovany A Gomes, Valdevane R Araújo, Selene M de Morais, Tigressa H S Rodrigues, José R V Silva","doi":"10.1093/jpp/rgae093","DOIUrl":"10.1093/jpp/rgae093","url":null,"abstract":"Objectives: This study aims to evaluate the effects of Croton grewioides essential oil (CGEO) and anethole on follicle survival, growth, and oxidative stress in cultured bovine ovarian tissues.Methods: Ovarian tissues were cultured for 6 days in a medium supplemented with different concentrations (1, 10, 100, or 1000 µg mL-1) of CGEO or anethole and then, follicular survival and growth, collagen content, and stromal cell density in ovarian tissues cultured in vitro were evaluated by histology. The mRNA levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase 1 (GPX1), peroxirredoxin 6 (PRDX6), and nuclear factor erythroid 2-related factor 2 (NRF2) were evaluated by real-time PCR. The activity of SOD, CAT, glutathione peroxidase (GPx), and thiol concentrations were investigated.Key findings: Ovarian tissues cultured with 1 µg mL-1 CGEO or anethole had a higher percentage of healthy follicles than those cultured in a control medium (P < .05). The 1 µg mL-1 CGEO also increased the number of stromal cells, collagen fibers, and thiol levels. Anethole (1 µg mL-1) increased CAT activity and reduced that of GPx. The activity of SOD was reduced by CGEO. In contrast, 1 µg mL-1 anethole reduced mRNA for CAT, PRDX1, and NRF2 (P < .05). In addition, 1 µg mL-1 CGEO reduced mRNA for CAT, PRDX6, and GPx1 (P < .05).Conclusions: The presence of 1 µg mL-1 anethole or CGEO in a culture medium promotes follicle survival and regulates oxidative stress and the expression of mRNA and activity of antioxidant enzymes in cultured bovine ovarian tissues.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1609-1619"},"PeriodicalIF":2.8,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627029","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

Mesenchymal stem cell-derived exosomal microRNA-367-3p mitigates lower limb ischemia/reperfusion injury in mouse skeletal muscle via EZH2 targeting. 间充质干细胞衍生的外泌体microRNA-367-3p通过EZH2靶向缓解小鼠骨骼肌下肢缺血再灌注损伤

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2024-12-02 DOI: 10.1093/jpp/rgae086

Huanhuan Sun, Jueqiong Wang, Wei Bi, Feng Zhang, Kai Zhang, Xitao Tian, Xiang Gao, Yanrong Zhang

{"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":"Objective: 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.Methods: 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.Key findings: 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.Conclusions: 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.","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}

引用次数: 0

Production of mRNA lipid nanoparticles using advanced crossflow micromixing. 利用先进的横流微混合技术生产 mRNA 脂质纳米颗粒。

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2024-12-02 DOI: 10.1093/jpp/rgae122

Muattaz Hussain, Burcu Binici, Liam O'Connor, Yvonne Perrie

{"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":"Objectives: 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.Methods: 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).Key findings: 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.Conclusions: 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.","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}

引用次数: 0