Frontiers in Pharmacology最新文献

{"title":"The adjunctive role of metformin in patients with mild to moderate ulcerative colitis: a randomized controlled study.","authors":"Ammena Y Binsaleh, Sahar M El-Haggar, Sahar K Hegazy, Maha M Maher, Monir M Bahgat, Thanaa A Elmasry, Sarah Alrubia, Amsha S Alsegiani, Mamdouh Eldesoqui, Mostafa M Bahaa","doi":"10.3389/fphar.2025.1507009","DOIUrl":"10.3389/fphar.2025.1507009","url":null,"abstract":"<p><strong>Background: </strong>Metformin, hypoglycemic medication, is recognized for its diverse properties and its capacity to influence the inflammatory pathways. Medications with anti-inflammatory and anti-oxidative characteristics have been demonstrated to be able to elicit and sustain remission in ulcerative colitis (UC), chronic inflammatory disorder of the bowel. Studies in both preclinical and clinical settings have looked into the several metabolic pathways via which metformin protects against UC.</p><p><strong>Aim: </strong>To assess efficacy of metformin as adjunctive therapy in patients with mild to moderate UC.</p><p><strong>Methods: </strong>This clinical research was double-blinded, randomized, controlled, and involved 60 patients with mild to moderate UC. The participants were randomly assigned to one of two groups (n = 30). The control group was given 1 g of mesalamine three times a day (t.i.d.) for a period of 6 months (mesalamine group). The metformin group was given 500 mg of metformin twice daily and 1 g of mesalamine t. i.d. For a period of 6 months. Patients with UC were assessed by a gastroenterologist using the disease activity index (DAI) both at the beginning of treatment and 6 months thereafter. To evaluate the drug's biological efficacy, measurements of fecal calprotectin, serum C-reactive protein (CRP), interleukin 10 (IL-10), and nitric oxide (NO) were taken both before and after treatment.</p><p><strong>Study outcomes: </strong>Decrease in DAI and change in the level of measured serum and fecal markers.</p><p><strong>Results: </strong>The metformin group displayed a statistical reduction in DAI (<i>p</i> = 0.0001), serum CRP (<i>p</i> = 0.019), NO (<i>p</i> = 0.04), and fecal calprotectin (<i>p</i> = 0.027), as well as a significant increase in IL-10 (<i>p</i> = 0.04) when compared to the mesalamine group. There was a significant direct correlation between DAI and calprotectin (p < 0.0001, r = 0.551), and between DAI and CRP (p < 0.0001, r = 0.794). There was a significant negative correlation between DAI and IL-10 (p = 0.0003, r = 0.371).</p><p><strong>Conclusion: </strong>Metformin may be an effective adjunct drug in management of patients with mild to moderate UC by decreasing DAI and other inflammatory markers that were involved in the pathogenesis of UC.</p><p><strong>Clinical trial registration: </strong>identifier NCT05553704.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1507009"},"PeriodicalIF":4.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795190","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":"Mycotoxins and neuropsychiatric symptoms: possible role in special refugee populations.","authors":"Malvina Hoxha, Mariagrazia Abbasciano, Giuseppina Avantaggiato, Bruno Zappacosta, Domenico Tricarico","doi":"10.3389/fphar.2025.1524152","DOIUrl":"10.3389/fphar.2025.1524152","url":null,"abstract":"","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1524152"},"PeriodicalIF":4.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771966","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":"Prognostic and clinicopathological roles of circular RNA expression in chemoresistance in head and neck squamous cell carcinoma: a systematic review.","authors":"Sayan Kumar Das, Sameer Khasbage, Ashim Mishra, Babban Jee","doi":"10.3389/fphar.2025.1502107","DOIUrl":"10.3389/fphar.2025.1502107","url":null,"abstract":"<p><strong>Background: </strong>Characterized by a poor prognosis and survivability, head and neck squamous cell carcinoma (HNSCC) is an aggressive neoplastic condition with a propensity for recurrence where the development of chemoresistance adversely affects the prognostic outcome. Recently, it was shown that circular RNAs (circRNAs) augment the cellular survivability and chemoresistance of malignant cells. Hence, biomarkers for early detection of chemoresistance in these patients can significantly aid in preventing a poor prognostic outcome.</p><p><strong>Objective: </strong>The present study aimed to systematically identify circRNAs that play a vital role in the development of chemoresistance in HNSCC and understand their mechanisms of action in HNSCC chemoresistance.</p><p><strong>Methods: </strong>The protocol was prospectively registered on PROSPERO with protocol no. CRD42024532291. A six-stage methodological and PRISMA recommendations were followed for the review.</p><p><strong>Results and discussion: </strong>13 studies were identified which yielded 13 circRNAs which have been investigated for their role in the chemoresistance in HNSCC. Of these, 11 circRNAs were reported to be upregulated while only 2 circRNAs were found to be downregulated. Moreover, we found that circRNAs can modulate autophagy (circPARD3, circPKD2, circAP1M2 and circPGAM1), apoptosis (circ-ILF2, circANKS1B, circTPST2, circPUM1 and circ_0001971), drug efflux (circ-ILF2, has_circ_0005033 and circTPST2), EMT (circANKS1B, circCRIM1, circ_0001971), tumor microenvironment (circ-ILF2. circ-ILF2, circCRIM1 and circTPST2), DNA damage (circTPST2) and malignant potential (hsa_circ_0000190 and hg19_ circ_0005033).</p><p><strong>Conclusion: </strong>The present study identified 13 circRNAs which may serve as biomarkers for prognosis as well as response to chemotherapy in HNSCC.</p><p><strong>Systematic review registration: </strong>PROSPERO, identifier CRD42024532291.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1502107"},"PeriodicalIF":4.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771973","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":"Cost-effectiveness analysis of penpulimab combined with paclitaxel and carboplatin as first-line treatment for advanced squamous non-small cell lung cancer.","authors":"Xiaoyan You, Jiali Qin, Xiaomei Wang, Xianying Wang","doi":"10.3389/fphar.2025.1563788","DOIUrl":"10.3389/fphar.2025.1563788","url":null,"abstract":"<p><strong>Background: </strong>Advanced or metastatic squamous non-small cell lung cancer (NSCLC) represents a significant clinical and economic burden globally. In China, the introduction of innovative immunotherapy agents, such as penpulimab, has the potential to improve patient outcomes, but their high cost raises questions about affordability and cost-effectiveness.</p><p><strong>Objective: </strong>This study evaluates the economic viability of penpulimab combined with paclitaxel and carboplatin as a first-line treatment for this patient population.</p><p><strong>Methods: </strong>Data were obtained from the published randomized controlled trial AK105-302. A three-state partitioned survival model was developed to estimate the cost-effectiveness of the two treatments. One-way deterministic sensitivity analysis, probabilistic sensitivity analysis, and scenario analyses were performed to assess the robustness of the results and explore variations in key parameters.</p><p><strong>Results: </strong>The incremental cost-effectiveness ratio (ICER) for the penpulimab group compared to the placebo group was $16,105.90 per quality-adjusted life year (QALY), which falls below the willingness-to-pay (WTP) threshold of $37,709.46 per QALY. Deterministic sensitivity analysis identified the three most influential factors affecting model outcomes: discount rate, costs associated with progressive disease, and utility value for progression-free survival. Probabilistic sensitivity analysis indicated that at a WTP threshold of $37,709.46 per QALY, the probability of penpulimab being cost-effective reached 99%. Scenario analyses demonstrated that, while the base-case results were generally robust, the cost-effectiveness of penpulimab remained sensitive to the limited maturity of overall survival (OS) data in the penpulimab group. The immaturity of the OS data increased the extrapolation uncertainty, which could potentially alter the economic conclusions.</p><p><strong>Conclusion: </strong>Penpulimab, in combination with paclitaxel and carboplatin, demonstrates a cost-effectiveness advantage over placebo as a first-line treatment for advanced or metastatic squamous NSCLC in China, provided that long-term survival benefits align with extrapolations from the base case model. These findings support its prioritization in clinical practice within the current WTP thresholds. However, the economic conclusions remain contingent on resolving the uncertainties associated with immature OS data and validating extrapolation assumptions through extended follow-up studies.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1563788"},"PeriodicalIF":4.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803038","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":"Mitochondria and oxidative stress in epilepsy: advances in antioxidant therapy.","authors":"Delphine Ji, Shanthini Mylvaganam, Prathyusha Ravi Chander, Mark Tarnopolsky, Keiran Murphy, Peter Carlen","doi":"10.3389/fphar.2024.1505867","DOIUrl":"10.3389/fphar.2024.1505867","url":null,"abstract":"<p><p>Epilepsy, affecting approximately 50 million individuals worldwide, is a neurological disorder characterized by recurrent seizures. Mitochondrial dysfunction and oxidative stress are critical factors in its pathophysiology, leading to neuronal hyperexcitability and cell death. Because of the multiple mitochondrial pathways that can be involved in epilepsy and mitochondrial dysfunction, it is optimal to treat epilepsy with multiple antioxidants in combination. Recent advancements highlight the potential of antioxidant therapy as a novel treatment strategy. This approach involves tailoring antioxidant interventions-such as melatonin, idebenone, and plant-derived compounds-based on individual mitochondrial health, including mitochondrial DNA mutations and haplogroups that influence oxidative stress susceptibility and treatment response. By combining antioxidants that target multiple pathways, reducing oxidative stress, modulating neurotransmitter systems, and attenuating neuroinflammation, synergistic effects can be achieved, enhancing therapeutic efficacy beyond that of a single antioxidant on its own. Future directions include conducting clinical trials to evaluate these combination therapies, and to translate preclinical successes into effective clinical interventions. Targeting oxidative stress and mitochondrial dysfunction through combination antioxidant therapy represents a promising adjunctive strategy to modify disease progression and improve outcomes for individuals living with epilepsy.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1505867"},"PeriodicalIF":4.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771951","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>Rhus coriaria</i> (Sumac) induces autophagic cell death and inhibits mTOR, p38MAPK and STAT3 pathways in 5fluorouracil-resistant colorectal cancer cells.","authors":"Zohra Nausheen Nizami, Mazoun Al Azzani, Samah Khaldi, Adil Farooq Wali, Rym Magramane, Shamaa Abdul Samad, Ali H Eid, Kholoud Arafat, Yusra Al Dhaheri, Samir Attoub, Rabah Iratni","doi":"10.3389/fphar.2025.1542204","DOIUrl":"10.3389/fphar.2025.1542204","url":null,"abstract":"<p><strong>Introduction: </strong>Colorectal cancer is a leading cause of cancer related-death worldwide, and resistance to 5-fluorouracil (5FU, a key component of chemotherapy regimens, is a major clinical concern. We have previously elucidated the effects of <i>Rhus coriaria</i> ethanolic extract (RCE) in triple-negative breast cancer, CRC, and pancreatic cancer cells. Here, we explored the anticancer effects of RCE in parental (HCT-116-WT) and 5FU-resistant HCT-116 (HCT-116-5FU-R) CRC cells.</p><p><strong>Methods: </strong>MTT assay was used to assess cell viability. Muse analyzer was used to assess cell viability, cell cycle distribution, and apoptosis. Additionally, colony formation and growth assays and western blots were performed. <i>In vivo</i> effects of RCE were assessed by an <i>in ovo</i> chick embryo tumor growth assay.</p><p><strong>Results: </strong>We found that RCE inhibited the viability and colony formation and growth capacities of HCT-116-WT and HCT-116-5FU-R cells. The antiproliferative effects were attributed to DNA damage-mediated impairment of cell cycle at S phase, and induction of Beclin-1-independent autophagy in both cell lines. Mechanistically, inhibition of the mTOR, STAT3 and p38 MAPK pathways was implicated in the latter. Additionally, RCE induced caspase-7-independent apoptosis in HCT-116-WT cells. However, HCT-116-5FU-R cells were resistant to apoptosis through upregulation of survivin, and downregulation of Bax. Using autophagy and proteasome inhibitors, we clarified that autophagy and the proteasome pathway contributed to RCE-mediated cell death in HCT-116-WT and HCT-116-5FU-R cells. Lastly, we confirmed RCE inhibited the growth of both HCT-116-WT and HCT-116-5FU-R xenografts in a chick embryo model.</p><p><strong>Discussion: </strong>Collectively, our findings highlight that RCE is a source of phytochemicals that can be used as anticancer agents for 5FU-resistant CRC.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1542204"},"PeriodicalIF":4.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771881","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":"Editorial: Old drugs: confronting recent advancements and challenges.","authors":"Anna Wiktorowska-Owczarek, Diego Iacono, Magdalena Jasińska-Stroschein","doi":"10.3389/fphar.2025.1565890","DOIUrl":"10.3389/fphar.2025.1565890","url":null,"abstract":"","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1565890"},"PeriodicalIF":4.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771961","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":"The efficacy and safety of ginkgo terpene lactone preparations combined with antiplatelet aents in the treatment of ischemic stroke: a systematic review and meta-analysis.","authors":"Hong Xu, Li Zeng, Li Liao, Xiaoxuan Li, Yan Tang","doi":"10.3389/fphar.2025.1554207","DOIUrl":"10.3389/fphar.2025.1554207","url":null,"abstract":"<p><strong>Background: </strong>This meta-analysis aimed to assess the efficacy and safety of ginkgo terpene lactone preparations including diterpene ginkgolides meglumine injection (DGMI) and ginkgolide injection combined with antiplatelet drugs in the treatment of ischemic stroke.</p><p><strong>Methods: </strong>We systematically searched the randomized controlled trials(RCTs) with publication date earlier than 6 November 2024 in PubMed, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Journal Database (VIP), Chinese Biomedical Literature Database (CBM), Wanfang Database, Embase, Web of Science, ClinicalTrials.gov, and Cochrane Library. Studies were screened according to inclusion and exclusion criteria, evaluated according to criteria recommended by the Cochrane Handbook, and data were then analyzed using Stata 17 software.</p><p><strong>Results: </strong>Of 1,079 identified studies, 27 were eligible and included in our analysis (N = 3,336 patients). The meta-analysis demonstrated that the overall response rate [RR = 1.22, 95% CI(1.17, 1.27), Z = 9.76, <i>p</i> < 0.01], as well as the National Institutes of Health Stroke Scale (NIHSS) score and barthel index, were significantly better in the DGMI combined treatment group compared to the antiplatelet therapy alone group. However, there was no significant difference observed between the experimental group and the control group regarding improvements in prognosis and platelet function. The studies included in the analysis reported a total of 419 adverse reactions (ADRs), with 206 occurring in the DGMI combined treatment group; furthermore, there was no significant difference in the incidence of adverse events between the two groups.</p><p><strong>Conclusion: </strong>Ginkgo terpene lactone preparations, when combined with antiplatelet drugs, can significantly enhance the clinical efficacy of ischemic stroke and demonstrate a favorable safety profile. This combination is a potential treatment strategy that can improve the management of IS patients and has high clinical application value.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1554207"},"PeriodicalIF":4.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771978","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":"Exploring the antimicrobial, anti-inflammatory, antioxidant, and immunomodulatory properties of <i>Chrysanthemum morifolium</i> and <i>Chrysanthemum indicum</i>: a narrow review.","authors":"Yuqing Liang, Tengwen Liu, Dong Wang, Qingquan Liu","doi":"10.3389/fphar.2025.1538311","DOIUrl":"10.3389/fphar.2025.1538311","url":null,"abstract":"<p><p>Infectious diseases continue to be a major global public health concern, which is exacerbated by the increasing prevalence of antimicrobial resistance. This review investigates the potential of herbal medicine, particularly <i>Chrysanthemum morifolium</i> (CM) and <i>Chrysanthemum indicum</i> (CI), in addressing these challenges. Both herbs, documented in traditional Chinese medicine (TCM) and the Pharmacopoeia of the People's Republic of China (2020 edition), are renowned for their heat-clearing and detoxifying properties. Phytochemical studies reveal that these botanicals contain diverse bioactive compounds, including flavonoids, terpenoids, and phenylpropanoids, which exhibit antimicrobial, anti-inflammatory, and antioxidant properties, among other effects. Comparative analysis reveals that distinct compound profiles and differential concentrations of core phytochemicals between CM and CI may lead to differentiated therapeutic advantages in anti-infective applications. By systematically examining their ethnopharmacological origins, phytochemical fingerprints, and pharmacological mechanisms, this review highlights their synergistic potential with conventional antimicrobial therapies through multi-target mechanisms, proposing novel integrative approaches for global health challenges.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1538311"},"PeriodicalIF":4.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11963160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771974","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":"Editorial: Targeting cellular signalling pathways for disease therapy: the potential of cellular reprogramming and protein kinase inhibitors.","authors":"Vanessa Marensi, Pedro Fontes Oliveira, Ariane Zamoner","doi":"10.3389/fphar.2025.1580686","DOIUrl":"10.3389/fphar.2025.1580686","url":null,"abstract":"","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1580686"},"PeriodicalIF":4.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771963","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}