Frontiers in Pharmacology最新文献

{"title":"Nausea and vomiting as adverse events of oliceridine: a systematic review and meta-analysis of randomized controlled trials.","authors":"Jinfang Zeng, Shu Yang, Jinjin Jian, Minmin Zhu","doi":"10.3389/fphar.2026.1779641","DOIUrl":"https://doi.org/10.3389/fphar.2026.1779641","url":null,"abstract":"<p><strong>Background: </strong>Postoperative nausea and vomiting (PONV) continue to be some of the most common and troublesome complications following anesthesia. Oliceridine, a G protein-biased µ-opioid receptor agonist, has the potential to provide effective pain relief while reducing the incidence of opioid-associated side effects.</p><p><strong>Objectives: </strong>The aim of this study is to evaluate the effectiveness and safety of oliceridine for preventing PONV compared with morphine and a placebo.</p><p><strong>Methods: </strong>A comprehensive search was performed across PubMed/MEDLINE, Embase (Ovid), and the Cochrane Central Register of Controlled Trials (CENTRAL) from their inception up to 30 September 2025, without any language limitations. Randomized controlled trials (RCTs) comparing oliceridine with morphine or placebo were included. Outcomes included incidence of nausea, vomiting, and other opioid-related adverse events (ORAEs). Pooled risk ratios (RRs) and their corresponding 95% confidence intervals (CIs) were estimated using random-effects models.</p><p><strong>Results: </strong>This meta-analysis included five studies, with a total of 1,767 patients. The pooled analysis showed that oliceridine significantly reduced the incidence of postoperative nausea compared with morphine (risk ratio [RR] = 0.80; 95% confidence interval [CI] = 0.70-0.90). In dose-specific analyses, the RRs were 0.58 (95% CI = 0.50-0.67) for the 0.1 mg group, 0.82 (95% CI = 0.74-0.92) for the 0.35 mg group, and 1.00 (95% CI = 0.91-1.11) for the 0.5 mg group. Oliceridine also decreased the risk of postoperative vomiting (RR = 0.55; 95% CI = 0.45-0.67) relative to morphine. Subgroup analyses yielded RRs of 0.39 (95% CI = 0.31-0.50), 0.54 (95% CI = 0.38-0.78), and 0.80 (95% CI = 0.68-0.95) for the 0.1 mg, 0.35 mg, and 0.5 mg groups, respectively. Moreover, oliceridine appeared to lower the incidence of opioid-related adverse events, including dizziness (RR = 0.89; 95% CI = 0.76-1.04), dry mouth (RR = 0.50; 95% CI = 0.37-0.69), pruritus (RR = 0.50; 95% CI = 0.35-0.70), and somnolence (RR = 0.61; 95% CI = 0.45-0.82). Based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, the certainty of evidence ranged from moderate to low.</p><p><strong>Conclusion: </strong>Oliceridine, particularly at 0.1-0.35 mg demand doses, reduces PONV and several opioid-related adverse events compared with morphine while maintaining effective analgesia. However, compared with placebo, typical opioid adverse effects remain. Further large-scale RCTs are warranted.</p><p><strong>Systematic review registration: </strong>https://www.crd.york.ac.uk/PROSPERO/view/CRD42024604703, identifier PROSPERO (CRD42024604703).</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"17 ","pages":"1779641"},"PeriodicalIF":4.8,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13144020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resurgence of Chikungunya virus: rising global threat and challenges in its mitigation.","authors":"Priyadarshi Soumyaranjan Sahu, Ritesh Pattnaik, Mohammed Alissa, Ghadah S Abusalim, Alaa S Alhegaili, Ghfren S Aloraini, Abdulkarim S Binshaya, Ghada M Alnafesah, Subrat Kumar","doi":"10.3389/fphar.2026.1757035","DOIUrl":"https://doi.org/10.3389/fphar.2026.1757035","url":null,"abstract":"<p><p>Chikungunya virus (CHIKV) is an arthropod-borne viral disease which spreads to humans by mosquito bites, inducing musculoskeletal pain and fever. CHIKV was endemic to the Indian Ocean region till 2004 that affected millions. It has been expanding its existence to non-endemic regions in Europe, the Middle East and the Pacific regions since 2004. Current fast CHIKV transmission scenario highlights the necessity of innovating control methods and devising novel diagnostic techniques. Conventional vector control measures lack efficacy as CHIKV vector evolves. Also, the existing assays used to detect CHIKV vary on sensitivity and specificity. This leads to mis-reporting or under-reporting of CHIKV cases especially in the endemic regions. This review discusses the CHIKV pathogenesis, an overview of various existing detection and the mitigation measures. Later, the challenges and limitations posed by these and how they can be subjugated by employing various simple and sustainable measures are emphasised. This review also suggests strategies to deploy novel systems in resource-limited settings to effectively address the infection and transmission of CHIKV disease.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"17 ","pages":"1757035"},"PeriodicalIF":4.8,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunomodulatory functions of ginsenosides in skin diseases: molecular mechanisms and therapeutic prospects.","authors":"Donglin Yuan, Jiaxin Li, Zian Wang, Yu Han, Xue Yu, Zhendong Wei, Binbin Hou","doi":"10.3389/fphar.2026.1783370","DOIUrl":"https://doi.org/10.3389/fphar.2026.1783370","url":null,"abstract":"<p><p>Ginsenosides, the primary bioactive constituents of <i>Panax ginseng</i> C.A.Mey. (Araliaceae), have attracted growing attention in dermatological research. A wide range of <i>in vitro</i> and <i>in vivo</i> studies has demonstrated that ginsenosides exert diverse biological effects encompassing anti-inflammatory, antioxidant, immunomodulatory, wound-healing, and antitumor activities. Given the multifactorial pathogenesis of most skin disorders, the multitarget potential of ginsenosides renders them particularly promising for cutaneous diseases. In this review, we summarize the chemical composition and classification of ginsenosides, as well as recent advances in their application against major skin conditions, including psoriasis, dermatitis, photoaging, chronic non-healing wounds, and skin melanoma. Mechanistically, ginsenosides modulate multiple signaling pathways related to inflammation, oxidative stress, skin barrier function, and tissue repair, such as NF-κB/NLRP3, PI3K/Akt/mTOR/MAPK, Nrf2/HO-1, and TGF-β/Smads. We also discuss the synergistic effects among different ginsenoside metabolites and their combined targeted interventions. Despite promising preclinical findings, challenges remain in clinical translation, such as low oral bioavailability and insufficient clinical evidence. Future studies should focus on novel delivery systems, precise target identification, and high-quality clinical trials to promote the development and application of ginsenoside-based therapies in dermatology.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"17 ","pages":"1783370"},"PeriodicalIF":4.8,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Rhaponticum</i> genus: a systematic review on traditional uses, phytochemical profiles and pharmacological activities.","authors":"Wurentuya, Huhezhula, Qirigeer, Shengtao Mei, Sirigunqiqige, Laxinamujila Bai, Ying Xin, Hongyan Hu","doi":"10.3389/fphar.2026.1770524","DOIUrl":"https://doi.org/10.3389/fphar.2026.1770524","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The genus &lt;i&gt;Rhaponticum&lt;/i&gt; (Asteraceae/Compositae) comprises 24 species worldwide and has long been utilized in traditional medicine for clearing heat, detoxification, relieving intestinal colic, and treating rheumatoid arthritis, neurasthenia, kidney deficiency, lumbago, and gastrointestinal disorders. Modern pharmacological studies have revealed its diverse bioactivities, including antihypertensive, hypolipidemic, immunomodulatory, neuroprotective, antitumor, hepatoprotective, cardioprotective, anti-inflammatory and anti-influenza effects. However, a comprehensive systematic review integrating its traditional uses, phytochemical metabolites and pharmacological activities is still lacking, which hinders its further development and rational utilization.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;This study aims to fill the existing research gap by systematically collating and summarizing the traditional medicinal applications, phytochemical compositions, and proven pharmacological activities of &lt;i&gt;Rhaponticum&lt;/i&gt; species, thereby laying a solid theoretical foundation for the subsequent development, utilization, and in-depth research of this genus.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This review aims to systematically summarize the traditional applications, phytochemical profiles, and pharmacological activities of &lt;i&gt;Rhaponticum&lt;/i&gt; species, provide a theoretical basis for their future development and utilization, and highlight the necessity of further investigations into this valuable genus.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This study was primarily conducted through comprehensive literature search and screening. The retrieval sources included ethnobotanical textbooks, peer-reviewed journals, and scientific databases such as PubMed, Web of Science, Scifinder, and Google Scholar. The search terms encompassed the genus &lt;i&gt;Rhaponticum&lt;/i&gt;, its representative species (e.g., &lt;i&gt;Rhaponticum uniflorum, Rhaponticum carthamoides&lt;/i&gt;). Literature screening was based solely on relevance to the focus of the review, with the past 4 decades.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;&lt;i&gt;Rhaponticum&lt;/i&gt; species have a centuries-old history of folk medicinal use, with different ethnic groups utilizing various medicinal parts to treat diverse diseases. A total of 217 metabolites have been isolated and identified from Rhaponticum, covering steroids, flavonoids, sesquiterpenoids, thiophenes, triterpenoids, and other classes. Consistent with traditional uses, modern pharmacological studies have confirmed their antihypertensive, hypolipidemic, antitumor, neuroprotective, anti-inflammatory, cardioprotective, hepatoprotective, antimicrobial, and anti-influenza activities.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Despite 24 documented &lt;i&gt;Rhaponticum&lt;/i&gt; species, research has predominantly focused on a limited number of Asian species. The material basis, mechanism of action, and therapeutic efficacy of many species remain unclear, and systematic studies on the bioactiv","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"17 ","pages":"1770524"},"PeriodicalIF":4.8,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13144093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perioperative local anesthetics as modulators of tumor progression and metastasis.","authors":"Xiaoyu Zheng, Huaying Wei","doi":"10.3389/fphar.2026.1793731","DOIUrl":"https://doi.org/10.3389/fphar.2026.1793731","url":null,"abstract":"<p><p>Cancer surgery remains a cornerstone of treatment for solid malignancies; however, perioperative factors increasingly emerge as critical modulators of tumor recurrence and metastasis. Accumulating evidence suggests that anesthesia techniques and analgesic strategies can profoundly influence tumor biology, immune competence, and long-term oncologic outcomes. In particular, opioids-while indispensable for perioperative analgesia-have been associated with enhanced tumor progression through direct stimulation of oncogenic signaling pathways and suppression of antitumor immunity. In contrast, regional anesthesia and local anesthetics have gained attention for their opioid-sparing properties and potential antitumor effects. Beyond effective analgesia, local anesthetics exert multifaceted actions on tumor progression by inhibiting voltage-gated sodium channels, attenuating inflammatory signaling, suppressing EGFR-driven oncogenic pathways, restraining mesenchymal stem cell-mediated tumor support, and preserving or enhancing antitumor immune responses. This review summarizes current preclinical and clinical evidence elucidating the mechanisms by which local anesthetics and regional anesthesia modulate tumor growth, metastasis, and immune surveillance. Understanding these perioperative interactions provides a compelling rationale for integrating anesthetic strategies into comprehensive oncologic care aimed at improving long-term cancer outcomes.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"17 ","pages":"1793731"},"PeriodicalIF":4.8,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Restoring redox homeostasis through S-adenosyl-L-methionine and B-vitamins co-supplementation alleviates ethanol induced hepato-pancreatic injury by regulating glutathione biosynthesis in C57BL/6J mice.","authors":"Prasanth Babu Nandagopal, Venkatraman Manickam","doi":"10.3389/fphar.2026.1761748","DOIUrl":"https://doi.org/10.3389/fphar.2026.1761748","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Alcohol use disorder(AUD) is a chronic condition responsible for more than 3 million deaths annually worldwide and contributes to the development of multiple systemic comorbidities. Chronic alcohol consumption promotes inflammatory responses, immune suppression, antioxidant dysregulation, and nutritional deficiencies, severely affecting organs such as the liver and pancreas. Disruption of methionine metabolism and antioxidant defenses, including reduced availability of S-adenosyl-L-methionine (SAMe) and essential B-vitamins, has been implicated in alcohol-induced oxidative stress. Therefore, the aim of the present study was to investigate whether co-supplementation with SAMe and B-vitamins could alleviate ethanol-induced hepato-pancreatic injury by improving redox homeostasis and glutathione biosynthesis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;C57BL/6J male mice (n = 6 per group) were used to model acute-on-chronic alcohol-associated liver injury using the NIAAA chronic-plus-binge ethanol feeding model. From days 1-10, mice were fed a Lieber-DeCarli liquid diet containing 5% (v/v) ethanol &lt;i&gt;(ad libitum)&lt;/i&gt; to establish chronic ethanol exposure while receiving co-supplementation with SAMe(5 mg/kg) and B-vitamins (B6-7 mg/kg; B12-50 μg/kg; B1-3.68 mg/kg). On day 11, mice received a single ethanol dose of 5 g/kg body weight by oral gavage as an acute binge ethanol exposure. Liver and pancreatic function was assessed by quantifying serum enzymatic markers. Oxidative and redox status was evaluated through biochemical estimation of nitric oxide, lipid peroxidation, hydrogen sulfide, and glutathione levels. Inflammatory responses were assessed by TNF-α quantification and NF-κB (p65) DNA-binding activity, while histopathological alterations were examined using H&E staining. Additionally, the expression of key genes (&lt;i&gt;Nos2, Gclc, Gpx1, and Cyp2e1&lt;/i&gt;) were analysed to corroborate the findings.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;SAMe and B-vitamin co-supplementation significantly attenuated ethanol-induced hepato-pancreatic injury, evidenced by reduced activities of amylase, alanine aminotransferase, and aspartate aminotransferase, myeloperoxidase (&lt;i&gt;p&lt;/i&gt; &lt; 0.001) and promoted restoration of tissue architecture. Inflammatory signalling was markedly suppressed, reflected by decreased NF-κB and TNF-α levels (&lt;i&gt;p&lt;/i&gt; &lt; 0.05), alongside a significant reduction in oxidative stress markers, including nitric oxide, lipid peroxidation, and &lt;i&gt;Cyp2e1&lt;/i&gt; expression (&lt;i&gt;p&lt;/i&gt; &lt; 0.001), collectively indicating a protective therapeutic effect.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Chronic ethanol exposure induces profound oxidative stress and impairs endogenous antioxidant defence system, culminating in severe hepato-pancreatic injury. Restoration of glutathione homeostasis and stabilization of cellular redox balance through SAMe and B-vitamins co-supplementation efficiently attenuated organ pathology, thereby improving the overall wellbeing ","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"17 ","pages":"1761748"},"PeriodicalIF":4.8,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patchouli alcohol suppresses <i>Helicobacter pylori</i>-associated gastric cancer by activating PXR to inhibit the Wnt/β-catenin pathway and EMT.","authors":"Xinyu Zhang, Qingling Zeng, Pengpeng Guo, Yifei Xu, Rui Ma, Jingwei Li","doi":"10.3389/fphar.2026.1794025","DOIUrl":"https://doi.org/10.3389/fphar.2026.1794025","url":null,"abstract":"<p><strong>Background: </strong><i>Helicobacter pylori</i> (HP) infection is a principal risk factor for gastric cancer, driving tumorigenesis through chronic inflammation, disruption of the epithelial barrier, and genomic instability. Patchouli alcohol (PA), the major bioactive constituent of <i>Pogostemon cablin</i>, exhibits anti-inflammatory, antioxidant, and antitumor properties; however, its role and underlying mechanisms in HP-associated gastric cancer remain poorly understood.</p><p><strong>Purpose: </strong>We hypothesized that HP infection suppresses the activity of the pregnane X receptor (PXR), thereby relieving its inhibitory effect on Wnt/β-catenin signaling and epithelial-mesenchymal transition (EMT), promoting gastric cancer invasiveness. PA was proposed as a PXR agonist capable of counteracting HP-induced malignant phenotypes via modulation of the PXR-Wnt/EMT axis.</p><p><strong>Methods: </strong>A multi-level integrative approach was employed: (1) single-cell transcriptomic analysis to characterize expression and regulatory features of the PXR-Wnt-EMT axis in HP-positive versus HP-negative gastric cancer epithelial cells; (2) virtual knockout and TCGA-STAD cohort analyses to assess the causal relationship between PXR and Wnt/EMT signaling; (3) molecular docking and 100 ns molecular dynamics simulations to evaluate PA binding to the PXR ligand-binding domain (LBD) and complex stability; (4) metabolomic and proteomic analyses in HP-associated gastric cancer models to validate PA-mediated modulation of metabolic networks and Wnt/EMT signaling.</p><p><strong>Results: </strong>Single-cell analysis revealed that HP-positive epithelial cells exhibited reduced PXR activity alongside upregulation of Wnt/β-catenin signaling and EMT transcription factors. Virtual PXR knockout recapitulated Wnt/EMT transcriptional activation, and TCGA-STAD analysis confirmed a significant negative correlation between PXR activity and Wnt/EMT signaling. Molecular docking and MD simulations demonstrated stable binding of PA to the PXR LBD. Metabolomic profiling revealed disrupted bile acid and lipid metabolism in HP model mice, partially restored by PA treatment. Proteomic and immunofluorescence analyses showed that PA downregulated Wnt pathway proteins (Dvl3, Tcf7l2) and mesenchymal EMT markers (N-cadherin, MMP9) while upregulating the Wnt inhibitor APC and epithelial marker E-cadherin, collectively reversing HP-induced Wnt/EMT hyperactivation.</p><p><strong>Conclusion: </strong>PA activates PXR through both direct and indirect mechanisms, thereby suppressing Wnt/β-catenin signaling and EMT, and ultimately inhibiting the initiation and progression of H. pylori-associated gastric cancer. This study elucidates the molecular link between HP-induced PXR downregulation and aberrant Wnt/EMT activation, highlighting PA as a potential therapeutic and preventive candidate for HP-related gastric cancer.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"17 ","pages":"1794025"},"PeriodicalIF":4.8,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renal safety of postoperative short-term use of flurbiprofen axetil in well-controlled hypertensive patients: a prospective multicenter cohort study.","authors":"Liang Sun, Yuhui Jiang, Xiaoran Ma, Yanhong Liu, Yubo Xie, Xiaoxia An, Weidong Mi, Yi Feng","doi":"10.3389/fphar.2026.1773939","DOIUrl":"https://doi.org/10.3389/fphar.2026.1773939","url":null,"abstract":"<p><strong>Background: </strong>Currently, postoperative nonsteroidal anti-inflammatory drugs-associated kidney damage in hypertensive patients remains undetermined. This study aimed to examine renal safety of short-term post-surgery use of flurbiprofen axetil (FA) in well-controlled hypertensive patients.</p><p><strong>Methods: </strong>Data were collected from January 2020 to March 2021 at four major hospitals on patients who had undergone total knee replacement surgery (TKA). Patients were divided into well-controlled hypertensive and normotensive groups, and received short-term intravenous FA postoperatively. The primary outcomes were trajectory changes of postoperative renal injury biomarkers. Second outcomes included acute kidney injury (AKI), pain intensity and other complications.</p><p><strong>Results: </strong>A total of 120 patients were enrolled. Post-surgery FA significantly reduced pain in both groups. The results of repeated measures analysis of variance (ANOVA) demonstrated that the main effects of group, time and the group-by-time interaction on blood urea nitrogen (BUN), serum creatine (SCr) and Cystatin C (Cys C) levels were not statistically significant on postoperative day 2 and 5 (POD2 and POD5) (all P > 0.05). Urine N-acetyl-beta-glucosaminidase (NAG) levels were significantly higher on POD2 and POD5 in both groups [preoperative: (6.66 ± 4.87) U/L, POD2: (10.07 ± 6.88) U/L, POD5: (10.25 ± 7.68) U/L in normotensive group; preoperative: (7.39 ± 4.07) U/L, POD2: (12.34 ± 7.1) U/L, POD5: (15.57 ± 12.34) U/L in well-controlled hypertensive group; all P < 0.001] compared with baseline. However, only the well-controlled hypertensive group showed a continued increase in NAG levels on POD5 (P = 0.039). AKI occurred in 7.0% (4/57) and 3.2% (2/63) of well-controlled hypertensive and normotensive patients (P = 0.335), and all the AKI patients were at stage 1. After adjusting for confounding factors, hypertension had no impact on AKI (OR = 0.733, 95%CI: 0.074-7.222, P = 0.790). No significant differences in other complications were observed between the groups.</p><p><strong>Conclusion: </strong>The current FA regimen after surgery is effective, and it does not increase AKI incidence in well-controlled hypertensive TKA patients, thought posing a risk of tubular damage.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"17 ","pages":"1773939"},"PeriodicalIF":4.8,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the toxicological effects of exposure to polyethylene terephthalate on hepatocellular carcinoma: insights from network toxicology, molecular docking, molecular dynamics, and experimental validation.","authors":"Peng Chen, Xin Liu, Dongmei Yuan, Lan Zheng, Yumin Du, Dacai Gong, Xing Wei, Dan Wang, Ge Xu, Bin Ge","doi":"10.3389/fphar.2026.1772751","DOIUrl":"https://doi.org/10.3389/fphar.2026.1772751","url":null,"abstract":"<p><strong>Background: </strong>Polyethylene terephthalate (PET), one of the most widely used synthetic polymers globally, has emerged as a potential environmental risk factor for human health. However, the molecular mechanisms linking PET exposure to hepatocellular carcinoma (HCC) remain poorly understood.</p><p><strong>Methods: </strong>We adopted an integrated systems biology framework that combined computational target prediction (using ChEMBL, PharmMapper, and SwissTargetPrediction), transcriptomic profiling, and machine learning to elucidate key molecular targets and pathways involved in PET-associated hepatocarcinogenesis. Immune cell infiltration was assessed via CIBERSORT. Molecular docking followed by 100 ns molecular dynamics simulations were employed to verify protein-ligand binding interactions. The expression profiles and prognostic relevance of core genes were evaluated using TCGA-LIHC datasets. <i>In vitro</i> validation was carried out in two HCC cell lines (Hep3B and HepG2) through qRT-PCR, Western blotting, EdU incorporation assays, colony formation assays, and flow cytometric cell cycle analysis.</p><p><strong>Results: </strong>We identified 235 potential PET-interacting proteins, with 40 genes overlapping with HCC-associated genes. Integrated analysis consistently identified PLK1, CCNA2, and CDC25C as core mediators of PET-associated hepatocarcinogenesis. Molecular docking revealed potential binding interactions, with PLK1 showing the highest affinity (--8.0 kcal/mol). Molecular dynamics simulations confirmed sustained structural stability of these PET-protein complexes over 100 ns. Clinical data analysis demonstrated progressive upregulation of these genes with advancing tumor stage and grade, with high expression predicting poor overall survival. PET treatment of Hep3B and HepG2 cells significantly upregulated PLK1, CCNA2, and CDC25C expression at both mRNA and protein levels, enhanced colony formation capacity, increased EdU-positive cells, and promoted G2/M phase progression. Western blotting further revealed upregulation of the proliferation marker PCNA. Functional enrichment analysis revealed involvement of cell cycle regulation, metabolic reprogramming, and immune microenvironment remodeling. CIBERSORT analysis identified significant correlations between core gene expression and infiltration of neutrophils, monocytes, and macrophages, alongside negative associations with lymphoid populations.</p><p><strong>Conclusion: </strong>PET exposure may promote hepatocarcinogenesis through multi-layered mechanisms involving cell cycle dysregulation (primarily via PLK1, CCNA2, and CDC25C), metabolic reprogramming, and immune microenvironment remodeling. These findings provide mechanistic insights into plastic-associated cancer risk and identify potential biomarkers and therapeutic targets for populations with PET exposure.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"17 ","pages":"1772751"},"PeriodicalIF":4.8,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemical diversity and biological activities of marine sponges from the genus <i>Tedania</i>: a comprehensive review.","authors":"Geane Gabriele Oliveira Souza, José Walber Gonçalves Castro, Lariza Leisla Leandro Nascimento, Ana Maria Fernandes Duarte, Fázia Fernandes Galvão Rodrigues, José Galberto Martins Costa","doi":"10.3389/fphar.2026.1763267","DOIUrl":"https://doi.org/10.3389/fphar.2026.1763267","url":null,"abstract":"<p><p>Given current public health concerns and the growing number of individuals affected by cancer, inflammatory diseases, and microbial infections, the identification of natural bioactive metabolites has become crucial as a therapeutic alternative. Marine sponges stand out in this context due to their ability to produce diverse bioactive metabolites. The genus <i>Tedania</i> aligns with this perspective, as literature reports associate it with cytotoxic, anti-inflammatory, and antimicrobial properties. This integrative review aimed to compile studies on the chemical and biological composition of the genus <i>Tedania</i>, correlating molecular structure with biological activity while updating existing knowledge. The databases ScienceDirect, PubMed, LILACS, and Web of Science were searched using the keyword \"<i>Tedania\"</i>. Inclusion criteria comprised articles reporting the identification or isolation of metabolites and/or biological activities, while duplicate and unrelated articles were excluded. A total of 135 compounds were identified for the genus <i>Tedania</i>, with lipids predominating (55.55%), followed by alkaloids (21.48%), carotenoids (8.15%), and terpenes (4.44%). Metabolites <b>20</b>, <b>21</b>, and <b>22</b> were detected in three species of the genus. Most of the identified metabolites have not been biologically evaluated; however, alkaloids stood out among those that have been analyzed. Certain substances, fractions, and extracts were tested against various cancer cell lines and pathogenic microorganisms, including assessments of larvicidal activity and key signaling pathways. Regarding the biotechnological potential of the genus <i>Tedania</i>, the literature reports three patents with pharmacological applications. Therefore, sponges of the genus <i>Tedania</i> represent promising sources of bioactive metabolites with antiproliferative, antimicrobial, larvicidal, and anti-inflammatory effects, which warranting further scientific investigation.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"17 ","pages":"1763267"},"PeriodicalIF":4.8,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}