Sai Zhang, Zhuyuan Si, Mingkun Liu, Wenjuan Hao, Tong Xia, Zeyang Liu, Gang Du, Bin Jin
{"title":"Ginkgolic acid inhibits CD8<sup>+</sup> T cell activation and induces ferroptosis by lactate dehydrogenase A to exert immunosuppressive effect.","authors":"Sai Zhang, Zhuyuan Si, Mingkun Liu, Wenjuan Hao, Tong Xia, Zeyang Liu, Gang Du, Bin Jin","doi":"10.1016/j.jpha.2025.101233","DOIUrl":"10.1016/j.jpha.2025.101233","url":null,"abstract":"<p><p>In the context of the development of transplant oncology, it is of great clinical significance to find a drug with both antitumor and immunosuppressive effects for liver transplantation patients with hepatocellular carcinoma (HCC). The antitumor effect of ginkgolic acid (GA) has been confirmed, and some studies suggest that GA may also have an immunosuppressive effect. The immunosuppressive effect of GA was evaluated by histopathology, T-cell subpopulation, and cytokine detection in rat liver transplantation and mouse cardiac transplantation models, and transcriptomic and metabolomic analysis was used to explore the underlying mechanism of the GA immunosuppressive effect. Metabolites, activation, and ferroptosis markers of CD8<sup>+</sup> T cells were detected <i>in vivo</i> and <i>in vitro</i>. Based on rat liver transplantation and mouse cardiac transplantation models, the immunosuppressive effect of GA was first confirmed by histopathology, T-cell subpopulation, and cytokine detection. In the mouse cardiac transplantation model, transcriptomics combined with metabolomics demonstrated for the first time that GA inhibited lactate dehydrogenase A (LDHA) expression and pyruvate metabolism in CD8<sup>+</sup> T cells. It was confirmed <i>in vivo</i> and <i>in vitro</i> that GA inhibited pyruvate metabolism of CD8<sup>+</sup> T cells through LDHA, inhibiting their activation and inducing ferroptosis. Overexpression of LDHA partially reversed the effect of GA on the metabolism, activation, and ferroptosis of CD8<sup>+</sup> T cells <i>in vitro</i>. GA mediates metabolic reprogramming through LDHA to inhibit the activation and induce ferroptosis of CD8<sup>+</sup> T cells to exert an immunosuppressive effect, which lays an experimental foundation for the future clinical application of its immunosuppressive effect.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 7","pages":"101233"},"PeriodicalIF":8.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12303057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Greenness evaluation metric for analytical methods and software.","authors":"Tong Xin, Luyao Yu, Wenying Zhang, Yingxia Guo, Chuya Wang, Zhong Li, Jiansong You, Hongyu Xue, Meiyun Shi, Lei Yin","doi":"10.1016/j.jpha.2025.101202","DOIUrl":"10.1016/j.jpha.2025.101202","url":null,"abstract":"<p><p>The focus of green analytical chemistry (GAC) is to minimize the negative impacts of analytical procedures on human safety, human health, and the environment. Several factors, such as the reagents used, sample collection, sample processing, instruments, energy consumed, and the quantities of hazardous materials and waste generated during analytical procedures, need to be considered in the evaluation of the greenness of analytical assays. In this study, we propose a greenness evaluation metric for analytical methods (GEMAM). The new greenness metric is simple, flexible, and comprehensive. The evaluation criteria are based on both the 12 principles of GAC (SIGNIFICANCE) and the 10 factors of sample preparation, and the results are presented on a 0-10 scale. The GEMAM calculation process is easy to perform, and its results are easy to interpret. The output of GEMAM is a pictogram that can provide both qualitative and quantitative information based on color and number.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 7","pages":"101202"},"PeriodicalIF":8.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12318332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144777388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"pH-responsive biomimetic zeolitic imidazolate framework-based nanoparticles for co-delivery of cetuximab and siRNA in synergistic therapy of laryngeal squamous cell carcinoma.","authors":"Liyin Wang, Milad Ashrafizadeh, Gautam Sethi, Xinjia Zhou","doi":"10.1016/j.jpha.2025.101203","DOIUrl":"10.1016/j.jpha.2025.101203","url":null,"abstract":"<p><p>Suboptimal treatment of laryngeal squamous cell carcinoma (LSCC) provides poor survival rate. The poor bioavailability, resistance to cetuximab (Cet), and the instability of small interfering RNA (siRNA) limit their efficacy in LSCC therapy. The present study has been aimed to develop a Cet and focal adhesion kinase (FAK) siRNA (siFAK) co-delivery nanosystem. Zeolitic imidazolate framework-8 (ZIF-8), with its large specific surface area and pH-responsive properties, is an ideal delivery carrier allowing controlled drug release in the acidic tumor microenvironment. Therefore, Cet was loaded onto ZIF-8 and encapsulated in a TU177 cell membrane (TCM) after the electrostatic adsorption of siFAK. Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM), zeta potential, X-ray diffraction, and particle size analyses were deployed to characterize Cet/siFAK@ZIF-8@TCM. TU177 cells and subcutaneously transplanted tumor-bearing nude mice were used to evaluate the intracellular uptake, cytotoxicity, <i>in vivo</i> biocompatibility, biodistribution, biosafety, pH responsiveness, and anti-LSCC efficacy of Cet/siFAK@ZIF-8@TCM. After ZIF-8@TCM were loaded with Cet and siFAK, alterations in their physical and crystal structures, particle size, and zeta potential were observed. Meanwhile, the co-delivery system increased the loading of Cet through the electrostatic adsorption of siFAK to Cet-loaded ZIF-8. The intracellular uptake of Cet/siFAK@ZIF-8@TCM also protected siFAK from degradation, effectively decreasing the messenger RNA (mRNA) and protein expression levels of FAK in LSCC cells. The ZIF-8@TCM nanosystem for co-delivery of Cet and siFAK exhibited pH-responsiveness and tumor-targeting capabilities, thereby exerting anti-LSCC effects. Co-delivery of Cet and siFAK via the pH-responsive ZIF-8@TCM system enabled the targeted release of the chemotherapeutic and gene, in turn maximizing their anti-LSCC effect while ensuring biosafety.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 7","pages":"101203"},"PeriodicalIF":8.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12305587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144746717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"PU.1 regulation of type 1 dendritic cell function via NF-κB pathway in inhibition of non-small cell lung cancer progression.","authors":"Tingting Wang, Yishuo Li, Qiongyu Duan, Chunlei Wang, Yixian Wang, Tianyu Hu","doi":"10.1016/j.jpha.2024.101154","DOIUrl":"10.1016/j.jpha.2024.101154","url":null,"abstract":"<p><p>This research investigates the regulatory role of the transcription factor PU.1 in type 1 conventional dendritic cells (cDC1) and its therapeutic potential of modulating the nuclear factor kappaB (NF-κB) cells signaling pathway in non-small cell lung cancer (NSCLC). Utilizing single-cell transcriptome sequencing and comprehensive bioinformatics tools, including the CIBERSORT algorithm, we analyzed the immune cell landscape within NSCLC tissues. Our analysis revealed distinct NSCLC subtypes and delineated the developmental trajectories and functional distinctions of cDC1 cells. Key differentially expressed genes (DEGs) and pivotal functional modules within these cells were identified, highlighting PU.1 as a critical mediator underexpressed in NSCLC samples. Functionally, PU.1 demonstrated the induction of the NF-κB pathway, which led to inhibited tumor proliferation and enhanced activation of cDC1, thereby suggesting its role in tumor immune surveillance. <i>In vivo</i> models confirmed the suppressive effect of PU.1 on NSCLC progression, mediated through its influence on cDC1 functionality via the NF-κB pathway. These findings propose PU.1 as a promising target for NSCLC therapeutic strategies, emphasizing the importance of transcriptional regulators in the tumor microenvironment.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 7","pages":"101154"},"PeriodicalIF":8.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aleš Marek, Břetislav Brož, Michal Kriegelstein, Gabriela Nováková, Jana Hojcsková, Miroslava Blechová, Lenka Žáková, Jiří Jiráček, Lenka Maletínská
{"title":"Late-stage labeling of diverse peptides and proteins with iodine-125.","authors":"Aleš Marek, Břetislav Brož, Michal Kriegelstein, Gabriela Nováková, Jana Hojcsková, Miroslava Blechová, Lenka Žáková, Jiří Jiráček, Lenka Maletínská","doi":"10.1016/j.jpha.2025.101198","DOIUrl":"10.1016/j.jpha.2025.101198","url":null,"abstract":"<p><p>The preparation of specifically iodine-125 (<sup>125</sup>I)-labeled peptides of high purity and specific activity represents a key tool for the detailed characterization of their binding properties in interaction with their binding partners. Early synthetic methods for the incorporation of iodine faced challenges such as harsh reaction conditions, the use of strong oxidants and low reproducibility. Herein, we review well-established radiolabeling strategies available to incorporate radionuclide into a protein of interest, and our long-term experience with a mild, simple and generally applicable technique of <sup>125</sup>I late-stage-labeling of biomolecules using the Pierce iodination reagent for the direct solid-phase oxidation of radioactive iodide. General recommendations, tips, and details of optimized chromatographic conditions to isolate pure, specifically <sup>125</sup>I-mono-labeled biomolecules are illustrated on a diverse series of (poly)peptides, ranging up to 7.6 kDa and 67 amino acids (aa). These series include peptides that contain at least one tyrosine or histidine residue, along with those featuring disulfide crosslinking or lipophilic derivatization. This mild and straightforward late-stage-labeling technique is easily applicable to longer and more sensitive proteins, as demonstrated in the cases of the insulin-like growth factor binding protein-3 (IGF-BP-3) (29 kDa and 264 aa) and the acid-labile subunit (ALS) (93 kDa and 578 aa).</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 7","pages":"101198"},"PeriodicalIF":8.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12310069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yanxin Pan, Ning Ji, Lu Jiang, Yu Zhou, Xiaodong Feng, Jing Li, Xin Zeng, Jiongke Wang, Ying-Qiang Shen, Qianming Chen
{"title":"GPCRs identified on mitochondrial membranes: New therapeutic targets for diseases.","authors":"Yanxin Pan, Ning Ji, Lu Jiang, Yu Zhou, Xiaodong Feng, Jing Li, Xin Zeng, Jiongke Wang, Ying-Qiang Shen, Qianming Chen","doi":"10.1016/j.jpha.2024.101178","DOIUrl":"10.1016/j.jpha.2024.101178","url":null,"abstract":"<p><p>G protein-coupled receptors (GPCRs) are the largest family of membrane proteins in eukaryotes, with nearly 800 genes coding for these proteins. They are involved in many physiological processes, such as light perception, taste and smell, neurotransmitter, metabolism, endocrine and exocrine, cell growth and migration. Importantly, GPCRs and their ligands are the targets of approximately one third of all marketed drugs. GPCRs are traditionally known for their role in transmitting signals from the extracellular environment to the cell's interior via the plasma membrane. However, emerging evidence suggests that GPCRs are also localized on mitochondria, where they play critical roles in modulating mitochondrial functions. These mitochondrial GPCRs (mGPCRs) can influence processes such as mitochondrial respiration, apoptosis, and reactive oxygen species (ROS) production. By interacting with mitochondrial signaling pathways, mGPCRs contribute to the regulation of energy metabolism and cell survival. Their presence on mitochondria adds a new layer of complexity to the understanding of cellular signaling, highlighting the organelle's role as not just an energy powerhouse but also a crucial hub for signal transduction. This expanding understanding of mGPCR function on mitochondria opens new avenues for research, particularly in the context of diseases where mitochondrial dysfunction plays a key role. Abnormalities in the phase conductance pathway of GPCRs located on mitochondria are closely associated with the development of systemic diseases such as cardiovascular disease, diabetes, obesity and Alzheimer's disease. In this review, we examined the various types of GPCRs identified on mitochondrial membranes and analyzed the complex relationships between mGPCRs and the pathogenesis of various diseases. We aim to provide a clearer understanding of the emerging significance of mGPCRs in health and disease, and to underscore their potential as therapeutic targets in the treatment of these conditions.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 7","pages":"101178"},"PeriodicalIF":8.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12284666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144710442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Biological exposure and health risks of arsenic species from medicinal leeches at major exposure points in humans.","authors":"Yaolei Li, Jing Fan, Hailiang Li, Xianlong Cheng, Hongyu Jin, Feng Wei, Shuangcheng Ma","doi":"10.1016/j.jpha.2024.101177","DOIUrl":"10.1016/j.jpha.2024.101177","url":null,"abstract":"<p><p>Image 1.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 7","pages":"101177"},"PeriodicalIF":8.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12305576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144746713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exosomes in ovarian cancer: Impact on drug resistance and advances in SERS detection techniques.","authors":"Biqing Chen, Xiaohong Qiu, Yang Li","doi":"10.1016/j.jpha.2024.101170","DOIUrl":"10.1016/j.jpha.2024.101170","url":null,"abstract":"<p><p>Ovarian cancer is a prevalent gynecological malignancy with high mortality and low survival rates. The absence of specific symptoms in early stages often leads to late-stage diagnoses. Standard treatment typically includes surgery followed by platinum and paclitaxel chemotherapy. Exosomes, nanoscale vesicles released by various cell types, are key in intercellular communication, carrying biologically active molecules like proteins, lipids, enzymes, mRNA, and miRNAs. They are involved in tumor microenvironment remodeling, angiogenesis, metastasis, and chemoresistance in ovarian cancer. Emerging research highlights exosomes as drug carriers and therapeutic targets to suppress anti-tumor immune responses. Surface-enhanced Raman scattering (SERS) enables multiplexed, sensitive, and rapid detection of exosome surface proteins, offering advantages such as low background noise, no photobleaching, robustness, and high sensitivity over other detection methods. This review explores the relationship between exosomes and chemoresistance in ovarian cancer, examining the mechanisms by which exosomes contribute to drug resistance and their clinical implications. The goal is to provide new insights into chemoresistance mechanisms, improve diagnosis and intervention strategies, and enhance chemotherapy sensitivity in clinical treatments. In addition, the prospects of exosomes as drug carriers to resist chemical resistance and improve the survival of ovarian cancer patients are summarized. This article emphasizes the role of SERS in detecting ovarian cancer exosomes and advances in exosome detection.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 7","pages":"101170"},"PeriodicalIF":8.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12318317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144777387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Runan Zuo, Linran Fu, Wanjun Pang, Lingqing Kong, Liangyun Weng, Zeyuan Sun, Ruichao Li, Shaoqi Qu, Lin Li
{"title":"Self-assembled and intestine-targeting florfenicol nano-micelles effectively inhibit drug-resistant <i>Salmonella typhimurium,</i> eradicate biofilm, and maintain intestinal homeostasis.","authors":"Runan Zuo, Linran Fu, Wanjun Pang, Lingqing Kong, Liangyun Weng, Zeyuan Sun, Ruichao Li, Shaoqi Qu, Lin Li","doi":"10.1016/j.jpha.2025.101226","DOIUrl":"10.1016/j.jpha.2025.101226","url":null,"abstract":"<p><p>Antimicrobial resistance (AMR) is a growing public health crisis that requires innovative solutions. Emerging multidrug resistant (MDR) <i>Salmonella typhimurium</i> has raised concern for its effect on pathogenic infection and mortality in humans caused by enteric diseases. To combat these MDR <i>Salmonella typhimurium</i> pathogens, highly effective and broad-spectrum antibiotics such as flufenicol (FFC) need to be evaluated for their potent antibacterial activity against <i>Salmonella typhimurium</i>. However, the low solubility and low oral bioavailability of flufenicol need to be addressed to better combat AMR. In this work, we develop a novel nano-formulation, flufenicol nano-micelles (FTPPM), which are based on d-α-tocopherol polyethylene glycol 1,000 succinate (TPGS)/poloxamer 188 (P188), for the targeted treatment of biofilms formed by drug-resistant <i>Salmonella typhimurium</i> in the intestine. Herein, FTPPM were prepared via a thin film hydration method. The preparation process for the mixed micelles is simple and convenient compared with other existing nanodrug delivery systems, which can further decrease production costs. The optimized FTPPM demonstrated outstanding stability and sustained release. An evaluation of the <i>in vivo</i> anti-drug-resistant <i>Salmonella typhimurium</i> efficacy demonstrated that FTPPM showed a stronger efficacy (68.17 %) than did florfenicol-loaded TPGS polymer micelles (FTPM), flufenicol active pharmaceutical ingredients (FFC-API), and flufenicol commercially available medicine (FFC-CAM), and also exhibited outstanding biocompatibility. Notably, FTPPM also inhibited drug-resistant <i>Salmonella typhimurium</i> from forming biofilms. More importantly, FTPPM effectively restored intestinal flora disorders induced by drug-resistant <i>Salmonella typhimurium</i> in mice. In summary, FTPPM significantly improved the solubility and oral bioavailability of florfenicol, enhancing its efficacy against drug-resistant <i>Salmonella typhimurium</i> both <i>in vitro</i> and <i>in vivo</i>. FTPPM represent a promising drug-resistant <i>Salmonella typhimurium</i> treatment for curbing bacterial resistance via oral administration.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 7","pages":"101226"},"PeriodicalIF":8.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12329119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144801544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}