Pharmaceuticals最新文献

{"title":"DPPZ-Naphthalimide Conjugates as G-Quadruplex DNA Targeting Scaffolds: Design, Synthesis and Biomolecular Interaction Studies.","authors":"Ufuk Yildiz, Özge Gökçek","doi":"10.3390/ph19040575","DOIUrl":"10.3390/ph19040575","url":null,"abstract":"<p><p><b>Background:</b> Guanine-rich DNA regions can fold into G-quadruplex (G4) structures, which are prevalent in telomeres and oncogene promoters, making them attractive targets for anticancer therapeutics. Small molecules capable of selectively stabilizing G4 DNA can disrupt telomerase activity and oncogene expression, offering a promising strategy for cancer intervention. <b>Methods:</b> A rationally designed series of DPPZ-anhydride-conjugated ligands (<b>1</b> and <b>2</b>) and their corresponding quaternized derivatives (<b>1-q</b> and <b>2-q</b>) were synthesized to investigate the combined effects of π-extension, bromine substitution, and cationic modification on DNA recognition. The synthetic strategy relied on the incorporation of a highly planar DPPZ-anhydride scaffold to enhance π-surface area, followed by selective quaternization to introduce permanent positive charge and reinforce electrostatic interactions with the DNA backbone. All compounds were fully characterized by NMR and spectroscopic methods. The DNA-binding properties of the ligands were systematically evaluated toward duplex (ds-DNA) and G-quadruplex (G4-DNA) structures using UV-Vis absorption titration, fluorescence intercalator displacement (FID) assays, and competitive dialysis experiments. Quaternization markedly enhanced intrinsic binding constants and significantly reduced DC₅₀ values, particularly for G4-DNA. While bromine substitution increased overall binding affinity, it did not substantially improve topology selectivity. Among the series, compound <b>1-q</b> exhibited the most favorable balance between affinity and G4 selectivity. <b>Results:</b> The interaction of the compounds with BSA was quantified using Stern-Volmer quenching constants, which demonstrated a clear trend of enhanced quenching efficiency upon modification. The binding strength followed a descending order of <b>1-q</b> > <b>2-q</b> > <b>1</b> > <b>2</b>, highlighting the superior performance of the first series over the second. These findings indicate that the structural features of <b>1-q</b> facilitate a more robust interaction within the hydrophobic pockets of the protein. <b>Conclusions:</b> Overall, the results demonstrate that strategic π-conjugation combined with electrostatic reinforcement provides an effective approach for the development of topology-selective DNA-binding ligands.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular Risks of COVID-19 Therapeutics: Integrated Analysis of FAERS, Electronic Health Records, and Transcriptomics.","authors":"Xinran Zhu, Suguna Aishwarya Kuppa, Gibret Umeukeje, Robert Morris, Lan Bui, Kun Bu, Jie Zhang, Jin Wei, Feng Cheng","doi":"10.3390/ph19040574","DOIUrl":"10.3390/ph19040574","url":null,"abstract":"<p><p><b>Background/Objectives</b>: The purpose of this study was to investigate the association between cardiovascular adverse drug events (ADEs) and the use of COVID-19 medicines. <b>Methods</b>: The analyses were conducted by leveraging pharmacovigilance data from the Food and Drug Authority (FDA) Adverse Event Reporting System (FAERS) and TriNetX electronic health records (EHRs). Transcriptomic data from human embryonic stem cell-derived cardiomyocytes (hESC-CMs) exposed to remdesivir were analyzed to provide supportive biological context for the observed cardiovascular safety signals. <b>Results</b>: Comparative analysis of three approved COVID-19 therapies revealed that COVID-19 patients treated with remdesivir had a higher risk of cardiovascular events than those treated with Paxlovid or REGEN-COV. FAERS analysis further indicated that bradycardia, hypotension, and cardiac arrest were the most frequently reported cardiovascular events associated with remdesivir, which was validated by propensity score-matched EHR data. These findings suggest an association between remdesivir exposure and increased cardiovascular ADEs relative to other COVID-19 therapies. Sex-stratified analysis using FAERS and EHR did not show strong sex-dependent patterns for remdesivir-associated cardiovascular ADEs. Age-stratified analyses of EHR data showed age-associated variation across the three cardiovascular ADEs. Bradycardia displayed a non-uniform pattern with higher prevalence in the youngest and oldest age groups, hypotension showed an overall age-associated increase, and cardiac arrest showed only a weak age-associated effect. Pathway enrichment analysis on transcriptomic data revealed that the \"cGMP-PKG signaling pathway\", \"dilated cardiomyopathy\", and \"calcium signaling pathway\" were enriched among genes up-regulated by remdesivir exposure. <b>Conclusions</b>: In summary, our integrated analysis of pharmacovigilance, EHR, and transcriptomic data provides convergent evidence for associations between remdesivir and cardiovascular ADEs and offers biological context into these associations.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytochemical Analysis and Anticancer Activity of <i>Salvia chinensis Benth</i> in Colorectal Cancer: An Integrated Transcriptomic and Bioinformatic Study.","authors":"Long-Zhu Li, Xin-Yue Li, Zi-Yuan Wang, Tian-Qi Ma, Yan-Chao Wu, Hui-Jing Li","doi":"10.3390/ph19040569","DOIUrl":"10.3390/ph19040569","url":null,"abstract":"<p><p><b>Background/Objectives</b>: <i>Salvia chinensis Benth</i> (SJC), as a traditional medicinal plant, has garnered significant attention for its extensive pharmacological activities. However, a systematic investigation of its comprehensive chemical profile and the underlying mechanisms in colorectal cancer (CRC) remains to be elucidated. This study aims to elucidate the active compounds and targets responsible for the anti-colorectal cancer effects of the aqueous extract of SJC. <b>Methods:</b> An integrated strategy was employed. The chemical profile of the SJC aqueous extract was analyzed by UPLC-MS/MS. Its anticancer activities, including effects on cell proliferation, migration, and apoptosis, were evaluated using the HCT-116 CRC cell line. An integrated transcriptomic and bioinformatic approach, followed by protein-protein interaction (PPI) network analysis, was used to identify key molecular pathways and targets. Finally, molecular docking and cellular assays were performed to screen for potential bioactive compounds. <b>Results:</b> A total of 60 natural compounds were tentatively identified in SJC. SJC inhibited the proliferation, migration, and invasion of HCT-116 colorectal cancer cells. Through combined transcriptomic and bioinformatic analysis, four candidate key genes were initially identified. Further PPI network analysis prioritized CXCL8 as a key candidate among the four candidate targets. Molecular docking against CXCL8, together with subsequent cellular experiments, validated naringenin as a potential bioactive constituent contributing to the anti-CRC activity of SJC. <b>Conclusions:</b> This study provides a comprehensive chemical profile of SJC and offers significant insights into its potential anticancer mechanisms in CRC by identifying candidate targets and a potential bioactive constituent. While these findings are preliminary and require further experimental validation through additional CRC cell lines and in vivo models, they establish a solid foundation for future research into the therapeutic applications of SJC for colorectal cancer. These planned studies will help to further elucidate the underlying mechanisms and assess the translational potential of SJC.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Immunomodulatory Effects of Porcupine Bezoar on Cyclophosphamide-Induced Immunosuppression in Rats.","authors":"Ji Li, Wenbo Gao, Kien-Seng Lim, Song Lei, Zhipeng Chen, Xiao-Qing Sim, Qinqiang Long, Xue Xiao","doi":"10.3390/ph19040563","DOIUrl":"10.3390/ph19040563","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Immunosuppression is a serious side effect of chemotherapeutic agents such as cyclophosphamide (CTX) and significantly increases the risk of infection in patients. Porcupine (<i>Hystrix brachyura</i>) bezoar (PB), a traditional medicine derived from the Hystrix brachyura species of porcupine, is renowned for its antioxidant and anti-inflammatory properties. However, its immunomodulatory potential has not been adequately investigated. This study aimed to systematically evaluate the protective effects of PB against CTX-induced immunosuppression and the underlying mechanisms in a rat model. <b>Methods</b>: An immunosuppression model was established in rats through the injection of CTX. The effects of PB on immune function were evaluated through the measurement of serum immunoglobulin (IgA and IgG) and pro-inflammatory cytokine (IL-6 and TNF-α) levels, as well as through a histopathological examination of immune organs. The mechanisms were further elucidated by analysing changes in serum metabolites and gut microbiota composition using integrated metabolomics and 16S rRNA sequencing. <b>Results</b>: Treatment with PB significantly alleviated CTX-induced immunosuppression, as demonstrated by elevated serum levels of IgA and IgG and reduced concentrations of IL-6 and TNF-α. PB also improved the architecture of spleen and thymus tissues. Metabolomic analysis revealed that PB regulated glycerophospholipid metabolism and steroid hormone biosynthesis, thereby reducing pro-inflammatory metabolites such as prostaglandin F2α. Furthermore, PB modulated the gut microbiota, increasing the abundance of beneficial bacteria (e.g., <i>Bacteroidota</i> and <i>Lachnospiraceae</i>) and decreasing that of harmful bacteria (e.g., <i>Romboutsia</i> and <i>Clostridium sensu stricto</i>). <b>Conclusions</b>: This study demonstrates that PB can effectively counteract CTX-induced immunosuppression in rats. This immunomodulatory effect is linked to changes in the gut microbiota and the regulation of specific metabolic pathways. These findings provide a scientific basis for the potential use of PB as an immunoadjuvant therapy, offering new insights into the mechanisms of traditional medicines.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analytical and Clinical Validation of Action PharmaKitDx: A Comprehensive NGS Panel for the Identification of Pharmacogenetic Variants in Diverse Populations.","authors":"Luis Ramudo-Cela, Marta Izquierdo-García, María Dolores-Sequedo, Vicente Cubells-Perez, Sara Bernal, Pau Riera, Adriana Lasa, Laura Torres-Juan, Victor José Asensio, Iciar Martínez-López, Antonia Obrador de Hevia, Matías Morín, Miguel Ángel Moreno-Pelayo, Greta Carmona-Antoñanzas, Javier Porta Pelayo","doi":"10.3390/ph19040568","DOIUrl":"10.3390/ph19040568","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Pharmacogenomics (PGx) enables personalized therapy by identifying genetic variants that influence drug response. Despite the advantages of next-generation sequencing (NGS), few clinically validated, guideline-aligned panels comprehensively detect common, rare, and structurally complex pharmacogenetic variants. <b>Methods</b>: We developed and analytically validated Action PharmaKitDx, a targeted NGS panel covering 335 pharmacogenes, including all priority genes recommended by CPIC, DPWG, and CPNDS. Performance was assessed using Coriell HapMap and GeT-RM reference materials across multiple library preparation workflows and Illumina platforms. Clinical feasibility was evaluated in 41 patient samples from diverse specialties. Results were compared with established reference methods, including PCR-based assays, STR analysis, Sanger sequencing, and whole-exome sequencing. <b>Results</b>: Analytical validation: More than 99% of target bases achieved ≥30× coverage. Analytical accuracy, sensitivity, specificity, and positive predictive value exceeded 99.3%, with repeatability and reproducibility >99.7%. Concordance with GeT-RM haplotypes reached 98% after star-allele harmonization. The panel accurately detected complex variants, including <i>CYP2D6</i> copy-number changes and hybrid alleles. Clinical validation: Full concordance with prior genotyping was observed in clinical samples. Beyond the initial testing indication, each sample harbored a mean of six actionable variants (range 2-10). Thirty-six rare (minor allele frequency <1%) potentially actionable variants were additionally identified. <b>Conclusions</b>: Action PharmaKitDx demonstrates high analytical performance and broad clinical applicability, supporting its implementation as a scalable solution for comprehensive pharmacogenetic testing and precision prescribing.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sustainable Design and DoE-Based Optimization of Polymeric Systems for FDM 3D-Printed Indomethacin Amorphous Solid Dispersions.","authors":"Ioannis Pantazos, Christos Cholevas, Christos Vlachokostas, Afroditi Kapourani, Panagiotis Barmpalexis","doi":"10.3390/ph19040562","DOIUrl":"10.3390/ph19040562","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Amorphous solid dispersions (ASDs) produced via hot-melt extrusion (HME) and fused deposition modeling (FDM) 3D printing represent a promising strategy for improving the performance of poorly water-soluble drugs. However, the integrated HME-FDM workflow is inherently energy-intensive, and sustainability considerations are rarely incorporated into formulation and process optimization. The present study aimed to develop and optimize indomethacin (IND) ASDs using a systematic Design of Experiment (DoE) framework that integrates electrical energy consumption as a quantitative response alongside pharmaceutical performance attributes. <b>Methods</b>: Polymer-plasticizer miscibility was screened using hot-stage microscopy, followed by filament preparation via HME. A factorial DoE was applied to optimize drug loading and extrusion temperature considering electrical energy consumption, extrusion yield, encapsulation efficiency, and residual crystallinity. Solid-state characterization was performed using DSC and XRD. The optimized filament was subsequently subjected to geometry screening and a second DoE to optimize platform temperature, nozzle temperature, and printing speed with respect to printing time, electrical energy consumption, and drug assay. <b>Results</b>: Complete drug amorphization was achieved within a defined thermal window, with residual crystallinity governed by kinetic dissolution constraints at lower extrusion temperatures. Electrical energy demand during both HME and FDM was strongly influenced by thermal setpoints and process duration. Multi-response overlay analysis identified sustainability-oriented operating windows for both stages. Experimental validation confirmed close agreement between predicted and observed responses, demonstrating simultaneous reduction in electrical demand and maintenance of dose accuracy and solid-state stability. <b>Conclusions</b>: This study demonstrates that electrical energy consumption can be systematically embedded as a quantitative design variable in pharmaceutical process optimization. The proposed dual-stage DoE strategy establishes a rational framework for developing 3D-printed ASD dosage forms that balance molecular performance and environmental efficiency.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Edible Ultralong Organic Phosphorescent Maltodextrin with Different Dextrose Equivalents Values for Afterglow Visualizing the Quality of Tablets.","authors":"Zhijian Zhong, Haolong Xiong, Liangshan Ming, Yongmei Guan, Ailing Wen, Pengdi Cui, Caiyun Sun, Weifeng Zhu, Zhe Li","doi":"10.3390/ph19040565","DOIUrl":"10.3390/ph19040565","url":null,"abstract":"<p><p><b>Background:</b> This study deeply explores the influence of different dextrose equivalents (DE) values on room-temperature phosphorescence (RTP) properties of maltodextrin (MD) and its luminescence mechanism. The potential applications of MD tablets in non-destructive detection for afterglow visualizing are also explored. <b>Methods</b>: MD tablets with different DE values were prepared to investigate their RTP properties and afterglow effects. MD tablets were validated for afterglow signals and phosphorescence lifetimes under varying environmental conditions. Additionally, the unique afterglow effect of MD was used to detect the uniformity of tablets. Theoretical calculations of MD monomers and dimers were performed using time-dependent density functional theory. <b>Results</b>: The results demonstrated that MD with different DE values exhibited RTP properties, with phosphorescence lifetimes from 186.91 to 618.85 ms. The afterglow signals and phosphorescence lifetimes of MD tablets were influenced by multiple environmental conditions, i.e., relative humidity, temperature, oxygen, ultraviolet light, etc. Based on the afterglow effect of the MD, it is possible to non-destructively detect the uniform tablet. MD is an RTP material regulated by its DE value. Its phosphorescence mechanism is governed by a clustering-triggered emission mechanism, which is dominated by the rich hydrogen bond network. The material's stimuli-responsive properties and pronounced afterglow effect make it a potential application for non-destructive detection. <b>Conclusions</b>: This study not only investigates the stimulus-responsive behavior of MD but also discovers a common, safe, and edible stimulus-responsive RTP material. These findings provide a new method for non-destructive detection of drugs and reducing the potential pharmacological risks during production, storage, and transportation.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Preclinical Study of a PSMA Ligand-Based Dual-Modality Probe for Radical Prostatectomy.","authors":"Haoxi Zhou, Zhiqiang Chen, Long Yi, Baojun Wang, Shaoxi Niu, Yu Gao, Xu Zhang","doi":"10.3390/ph19040564","DOIUrl":"10.3390/ph19040564","url":null,"abstract":"<p><p><b>Purpose</b>: Prostate-specific membrane antigen (PSMA) is a well-established molecular target in prostate cancer (PCa). Both radionuclide imaging and near-infrared fluorescence (NIRF) imaging offer high sensitivity for in vivo tumor detection. PSMA-targeted dual-modality probes integrating these two imaging techniques provide complementary preoperative and intraoperative tumor visualization, thereby improving surgical guidance in PCa. In this study, we aimed to develop a novel dual-labeled PSMA probe combining radioactive and fluorescent properties to achieve precise tumor delineation during radical prostatectomy (RP). <b>Methods</b>: A high-affinity PSMA-targeted fluorescent probe (PSMA-DF) was synthesized using solid-phase synthesis. Subsequent radiolabeling with the radionuclide [⁶⁸Ga]Ga yielded the successful generation of a dual-modal PSMA-targeted molecular probe, namely [⁶⁸Ga]Ga-PSMA-DF. The probe was systematically evaluated both in vitro and in vivo, and its safety profile was assessed through acute toxicity testing. Tumor-bearing nude mouse models were established using PSMA-positive 22Rv1 and PSMA-negative PC-3 PCa cell lines. Imaging performance, tumor-targeting specificity, and biodistribution of the probe were comprehensively evaluated using micro-PET imaging, in vivo fluorescence imaging, and biodistribution studies. <b>Results</b>: High-quality and high-purity PSMA-DF was successfully prepared, which exhibited excellent optical properties. Following radiolabeling with [⁶⁸Ga]Ga, a dual-modality radionuclide-fluorescence probe ([⁶⁸Ga]Ga-PSMA-DF) was successfully constructed. In vitro cellular uptake studies demonstrated that 22Rv1 cells had relatively high uptake of the probe, reaching 7.34 ± 0.55 IA%/10⁶ cells at 120 min. In contrast, PC-3 cells and blocked 22Rv1 cells displayed minimal uptake, confirming the specific targeting ability of the probe. In vivo evaluations were conducted on tumor-bearing mice using micro-PET/CT and NIRF imaging. The results revealed that [⁶⁸Ga]Ga-PSMA-DF achieved high specific tumor accumulation in 22Rv1 xenografts, with the peak tumor uptake (SUVmax = 1.748 ± 0.132) and tumor-to-muscle ratio (11.542 ± 1.511) observed at 120 min. Notably, high-contrast fluorescence imaging was also achieved at later time points, yielding a tumor-to-background ratio (TBR) of 6.559 ± 1.415 at 48 h. Notably, ex vivo biodistribution data were consistent with in vivo imaging findings. <b>Conclusions</b>: This preclinical study demonstrates that [⁶⁸Ga]Ga-PSMA-DF exhibits high and specific uptake in PCa models, supporting its potential as a dual-modality tracer for both PET/CT imaging and real-time intraoperative fluorescence guidance during PCa surgery.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Cariogenic Effect of Trans-Cinnamaldehyde in an In Vitro Mouse Jaw Explant Model.","authors":"Zilefac Brian Ngokwe, Amit Wolfoviz-Zilberman, Galia Blum, Talya Hanna Avraham, Nurit Beyth, Yael Houri-Haddad, Dana Kesler-Shvero","doi":"10.3390/ph19040566","DOIUrl":"10.3390/ph19040566","url":null,"abstract":"<p><p><b>Background</b>: Dental caries, primarily caused by <i>Streptococcus mutans</i> (<i>S. mutans</i>), is a prevalent condition with significant global impact. Trans-cinnamaldehyde (TC), a phytochemical derived from the cinnamon plant, has shown promising antibacterial and antibiofilm activity against <i>S. mutans</i>. This study aimed to evaluate the anti-cariogenic effects of TC on <i>S. mutans</i> using an innovative mouse jaw explant model. <b>Methods</b>: TC was diluted in an organic solvent across various concentrations. Initially, cytotoxicity assays were performed at all tested TC concentrations. Sub-minimum bactericidal concentrations were then used to examine the distribution and morphology of <i>S. mutans</i> biofilms. Hemi-mandibles were dissected from euthanized, healthy, seven-week-old female mice to study the impact of TC on the cariogenic activity of <i>S. mutans</i> using stereoscopic analysis. Finally, pH changes during exposure to cariogenic conditions and post-treatment bacterial viability were measured. <b>Results</b>: In vitro data demonstrate that TC doses of ≤625 µg/mL were non-cytotoxic. Treatment groups exposed to TC exhibited altered bacterial morphology, including abnormal and incomplete cell division. In the mouse jaw explant model, TC doses of ≥625 µg/mL showed anti-cariogenic effects, evidenced by the absence of visible carious lesions. Additionally, pH changes and post-treatment viable bacterial counts corresponded with the observed anti-cariogenic activity. TC doses ≤625 µg/mL led to a pH drop over time and the presence of bacterial colonies. <b>Conclusions</b>: TC exhibits significant anti-cariogenic activity against <i>S. mutans</i> in the mouse model. Our findings suggest that 625 µg/mL is the lowest non-toxic concentration of TC that effectively inhibits cariogenic activity.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the Mechanism of Buyang Huanwu Decoction in Treating Ischemic Stroke by Regulating the NLRP3/Caspase-1 Signaling Pathway.","authors":"Keqi Zeng, Cong Nie, Xin Zhou, Die Pei, Jieyi Huang, Yingfeng Zhang","doi":"10.3390/ph19040567","DOIUrl":"10.3390/ph19040567","url":null,"abstract":"<p><p><b>Aim:</b> This study investigates how Buyang Huanwu Decoction (BHD) protects against cerebral ischemic damage by targeting the NLRP3/Caspase-1 pathway. <b>Methods:</b> The fingerprint of BHD was analyzed by HPLC-UV. Migratory chemicals in BHD-containing cerebrospinal fluid (BHD-CCSF) were analyzed by ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS). The effects of BHD on the NLRP3/Caspase-1 pathway, IL-18 and IL-1β levels in oxygen and glucose deprivation/reperfusion (OGD/R) cells were assessed by Western blot and ELISA. Cerebral infarction severity in permanent middle cerebral artery occlusion (pMCAO) mice was assessed by mNSS scores and staining. Protein and mRNA levels of the NLRP3/Caspase-1 pathway and inflammatory factors (IL-18, IL-1β) were measured. <b>Results:</b> BHD-containing serum (BHD-CS), BHD-CCSF, and Calycosin (Cal) reduced NLRP3, Caspase-1, ASC, GSDMD proteins, IL-18 and IL-1β in OGD/R cells. In pMCAO mice, BHD decreased pathway-related proteins and mRNA and inflammatory factors and alleviated brain injury. <b>Conclusions:</b> BHD ameliorates cerebral ischemia by inhibiting the NLRP3/Caspase-1 pathway, thereby suppressing pyroptosis and inflammation.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}