Frontiers in Pharmacology最新文献

{"title":"Non-small cell lung cancer after EGFR-TKI resistance: from drug resistance mechanisms to precision interventions.","authors":"Zhen Wang, Yanqi Song, Aidi Wang, Baoshan Liu","doi":"10.3389/fphar.2026.1795614","DOIUrl":"https://doi.org/10.3389/fphar.2026.1795614","url":null,"abstract":"<p><p>The emergence of epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) propelled EGFR-mutated patients of non-small cell lung cancer (NSCLC) into the era of precision medicine. Third-generation targeted therapies, such as osimertinib, can specifically target the T790M mutation and effectively overcome resistance to previous treatments, significantly prolonging progression-free survival in patients. Despite its remarkable clinical efficacy and manageable safety profile, it is still not immune to the development of resistance. Therefore, overcoming resistance and providing new treatment strategies for advanced NSCLC patients harboring EGFR mutations after osimertinib resistance are priorities that need to be considered. New-generation EGFR-TKIs or combination therapeutic strategies hold promise to address resistance. In addition, with the development of genomics and molecular diagnostic technologies, several drugs with novel mechanisms of action, such as antibody-drug conjugates and bispecific antibodies, have shown promising clinical response rates and favorable safety profiles in several clinical and experimental studies. This review aims to more systematically indicate the mechanisms of EGFR-TKI resistance and summarize the new strategies available and novel drugs under investigation for NSCLC patients harboring EGFR mutations after TKI resistance to extend their survival and improve quality of life.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"17 ","pages":"1795614"},"PeriodicalIF":4.8,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836399","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 ginseng berry saponin for heart failure: a systematic review and meta-analysis.","authors":"Jing Wang, Hongguang Jin, Tianying Chang, Yongsheng Huang, Yingzi Cui","doi":"10.3389/fphar.2026.1712401","DOIUrl":"https://doi.org/10.3389/fphar.2026.1712401","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Ginseng berry saponin (GBS), the primary bioactive constituent of &lt;i&gt;Panax ginseng&lt;/i&gt; C.A. Mey (known as \"Renshen\" in Chinese) berries, exhibits cardioprotective properties, including anti-inflammatory, antioxidant, and anti-fibrotic effects. In traditional Chinese medicine, they are widely used to treat various cardiovascular diseases. Several randomized controlled trials (RCTs) have shown its efficacy for heart failure (HF).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To assess the clinical efficacy and safety of GBS as an adjunct therapy for HF through systematic review and meta-analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A comprehensive and systematic literature search was conducted across seven electronic databases, with no language restrictions, from their respective inception dates through 31 March 2025. These databases included PubMed, the Cochrane Library, EMBASE, Web of Science China National Knowledge Infrastructure China Science and Technology Journal Database (VIP), and Wanfang Data. For quality assessment, the Cochrane Risk of Bias (ROB 2.0) tool was employed, and meta-analyses were performed using Review Manager (RevMan, version 5.4). Under a random-effects model, mean differences and their corresponding 95% confidence intervals (CI) were calculated. Additionally, the certainty of evidence for each outcome was systematically assessed using the GRADE methodology (GRADEpro software v3.6). The study has been registered in PROSPERO, with the registration number CRD420251003193.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The final analysis integrated 32 RCTs, comprising 3,476 HF patients for efficacy and safety assessment. Meta-analysis results indicated that adjunctive GBS therapy significantly improved the following outcomes compared with the control group (all P &lt; 0.01): LVEF (MD = 8.91, 95%CI [6.78, 11.04]), 6MWTD (MD = 63.11, 95%CI [43.27, 82.95]), FS (MD = 2.63, 95%CI [2.04, 3.22]), SV (MD = 6.68, 95%CI [5.56, 7.80]), Cardiac Index (MD = 0.51, 95%CI [0.33, 0.70]), CO (MD = 0.68, 95%CI [0.38, 0.99]), NO (MD = 10.82, 95%CI [7.49, 14.15]), FMD (MD = 2.42, 95%CI [1.45, 3.39]), and NMD (MD = 2.13, 95%CI [1.04, 3.21]). Conversely, adjunctive GBS therapy significantly reduced the following parameters (all P &lt; 0.01): LVEDD (MD = -5.71, 95%CI [-7.59, -3.82]), LVESD (MD = -6.30, 95%CI [-10.00, -2.59]), BNP (MD = -159.86, 95%CI [-199.17, -120.56]), NT-proBNP (MD = -529.13, 95%CI [-673.92, -384.33]), CRP (MD = -1.98, 95%CI [-2.25, -1.71]), hs-CRP (MD = -1.61, 95%CI [-2.66, -0.56]), TNF-α (MD = -20.42, 95%CI [-32.58, -8.26]), MMP-9 (MD = -34.76, 95%CI [-54.96, -14.56]), ET-1 (MD = -20.08, 95%CI [-30.18, -9.98]), SAS score (MD = -7.49, 95%CI [-11.43, -3.55]), SDS score (MD = -14.53, 95%CI [-17.26, -11.80]), HAMA score (MD = -4.48, 95%CI [-6.77, -2.20]), and HAMD score (MD = -5.79, 95%CI [-8.89, -2.68]).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This systematic review suggests that adjunctive GBS therapy may be associated with improvements in","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"17 ","pages":"1712401"},"PeriodicalIF":4.8,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13144151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835358","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":"A review of the protection mechanisms of ginsenoside CK on cardiovascular disease and stroke.","authors":"Hui-Ting Chan, Yu-Po Lee, Yu-Quan Chang, Lichieh Julie Chu, Tzu-Chun Tsai, Chin-Kuo Chen, Sheau-Long Lee, Guang-Huar Young, Yi-Huan Wu, Robert Y L Wang","doi":"10.3389/fphar.2026.1777145","DOIUrl":"https://doi.org/10.3389/fphar.2026.1777145","url":null,"abstract":"<p><p>Cardiovascular disease (CVD), comprising coronary artery disease, myocardial infarction, arrhythmias, heart failure, and hypertension, predominantly originates from dysfunction or obstruction within the cardiac and vascular systems. It has persistently remained the leading cause of death worldwide. The classification of stroke is based on its pathogenesis, with ischemic and hemorrhagic types representing distinct classifications. The etiology of stroke is attributed to cerebral vascular occlusion or rupture. It is frequently associated with hypoxic injury and neuronal necrosis, which poses a significant burden on individuals and public health systems. Ginsenoside compound K (CK), a secondary metabolite derived from the intestinal microbial transformation of protopanaxadiol type ginsenosides (e.g., Rb1, Rb2), exhibits high oral bioavailability and the capacity to cross the blood-brain barrier. Recent research has demonstrated that CK possesses antiplatelet and antithrombotic activities, inhibits vascular smooth muscle cell proliferation and endothelial inflammation, and shows low toxicity along with antiarrhythmic potential in the cardiovascular system. Furthermore, CK demonstrates significant anti-inflammatory, antioxidative, and mitochondrial protective properties, exhibiting efficacy in models of myocardial ischemia/reperfusion and cerebral ischemia. It exhibits good tolerability and safety without significant antagonism to other drugs and is increasingly recognized as a promising multi-target natural therapeutic candidate. The objective of this review is twofold: first, to synthesize recent findings on the mechanisms by which ginsenoside CK confers protection in cardiovascular and cerebrovascular conditions; and second, to assess its translational potential and highlight its prospective role in next-generation cardiovascular therapies.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"17 ","pages":"1777145"},"PeriodicalIF":4.8,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836293","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":"Multi-target tyrosine kinase inhibitor-associated renal thrombotic microangiopathy: a pooled analysis of 31 cases.","authors":"Miao Liu, Xingchen Zhou","doi":"10.3389/fphar.2026.1834421","DOIUrl":"https://doi.org/10.3389/fphar.2026.1834421","url":null,"abstract":"<p><strong>Background: </strong>Multi-target tyrosine kinase inhibitors (TKIs) are cornerstone therapies for solid malignancies, yet their association with renal thrombotic microangiopathy (TMA)-a severe, irreversible adverse event-remains incompletely defined. This study delineates TKI-associated renal TMA's clinical features, onset patterns, and outcomes.</p><p><strong>Methods: </strong>We systematically searched PubMed, Embase, Cochrane Library, and Web of Science for case reports/series of renal TMA linked to 7 multi-target TKIs (sunitinib, sorafenib, etc.) published through January 2026. Key data were extracted and analyzed descriptively.</p><p><strong>Results: </strong>Thirty-one cases were included (median age 62 years, 51.6% female). Common tumors: renal cell carcinoma (29.0%), thyroid cancer (16.1%), gastrointestinal stromal tumor (12.9%). Sunitinib was most implicated (48.4%). Median latency: 16 months (0.5-96 months); combination therapy shortened to 3.5 months. Dominant triad: hypertension (58.1%), AKI (77.4%), nephrotic proteinuria (67.9%); classic MAHA was uncommon. Kidney biopsy (87.1%) confirmed TMA. TKI discontinuation: 87.1% (6.5% dose reduction). Among evaluable patients, 90.0% improved, but 53.3% developed residual CKD and 10.0% ESRD.</p><p><strong>Conclusion: </strong>TKI-associated renal TMA presents as hypertension-proteinuria-AKI rather than classic hemolysis. Sunitinib confers highest risk, baseline hypertension is a key modifiable factor, and combination therapy accelerates onset. Lifelong monitoring and timely TKI discontinuation are critical, though residual CKD is common.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"17 ","pages":"1834421"},"PeriodicalIF":4.8,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13144059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836430","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":"Chinese herbal formulas as adjuncts to antihistamines in chronic spontaneous urticaria: a network meta-analysis of efficacy, recurrence, and safety.","authors":"Haiying Lv, Haoting Zhu, Huixia Mo, Jie Guo, Chuanjian Lu, Jingwen Deng","doi":"10.3389/fphar.2026.1718329","DOIUrl":"https://doi.org/10.3389/fphar.2026.1718329","url":null,"abstract":"<p><strong>Background: </strong>Chronic spontaneous urticaria (CSU) presents treatment challenges despite second-generation antihistamines (sgAHs) serving as the first-line therapy.</p><p><strong>Purpose: </strong>The aim of this network meta-analysis is to systematically evaluate the efficacy hierarchy and safety profile of classical traditional Chinese medicine (TCM) formulas used as adjuncts to antihistamines.</p><p><strong>Methods: </strong>We systematically evaluated 50 randomized controlled trials involving 5,814 patients using both Bayesian and frequentist network meta-analyses (NMAs) to compare the efficacy, recurrence, and safety of sgAHs alone or in combination with classical TCM formulas. The primary outcome was clinical improvement based on the Symptom Score Reducing Index (SSRI), with secondary outcomes including recurrence rates and adverse events (AEs). Risk of bias was assessed using RoB 2.0, and evidence certainty was evaluated using the CINeMA framework. Bayesian and frequentist NMA approaches were employed. Sensitivity analyses were conducted based on the study quality and prescription modifications.</p><p><strong>Results: </strong>Most combination regimens of classical TCM formulas were superior to antihistamine monotherapy for both SSRI ≥90% and ≥60% outcomes. Combinations involving <i>Danggui Yinzi, Yupingfeng powder,</i> and <i>Guizhi decoction</i> consistently ranked among the top in terms of efficacy. Among these regimens, loratadine or ebastine combined with <i>Danggui Yinzi</i> demonstrated the most pronounced reduction in recurrence risk, with the effect being more evident in the long-course subgroup (>12 weeks). Certain combination regimens, such as cetirizine combined with <i>Danggui Yinzi</i> and loratadine combined with <i>Guizhi decoction</i>, were associated with a reduced risk of AEs. However, no evaluated treatment showed a statistically significant advantage over cetirizine monotherapy in reducing IgE or IL-4 levels. The certainty of evidence for efficacy outcomes was predominantly moderate, whereas the overall certainty for safety outcomes was relatively low.</p><p><strong>Conclusion: </strong>In CSU management, classical TCM formulas, particularly <i>Danggui Yinzi, Yupingfeng powder,</i> and <i>Guizhi decoction,</i> may improve remission and reduce recurrence when combined with sgAHs without increasing the incidence of AEs. Further high-quality head-to-head trials are needed to confirm these findings.</p><p><strong>Systematic review registration: </strong>https://www.crd.york.ac.uk/PROSPERO, identifier CRD420251022634.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"17 ","pages":"1718329"},"PeriodicalIF":4.8,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13144053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836438","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":"Rhabdomyolysis associated with <i>Ophioglossum vulgatum</i> consumption: a case series and safety implications.","authors":"Xiaorong Li, Lindan Liao","doi":"10.3389/fphar.2026.1807082","DOIUrl":"https://doi.org/10.3389/fphar.2026.1807082","url":null,"abstract":"<p><strong>Background: </strong><i>O. vulgatum</i> (<i>Ophioglossum vulgatum</i>, commonly known as \"Yi Zhi Jian\") is a traditional herbal medicine and food ingredient widely used for its heat-clearing and detoxifying properties and generally considered safe. However, its potential for severe muscular toxicity, particularly rhabdomyolysis, has not been systematically reported.</p><p><strong>Case presentation: </strong>A retrospective case series analysis was conducted on 10 patients admitted to the First People's Hospital of Neijiang City from 2024 to 2025 with <i>O. vulgatum</i> poisoning complicated by rhabdomyolysis. All patients ingested <i>O. vulgatum</i> for the purpose of \"stewing soup\", with a median latency period of 7 h. The predominant symptoms were severe myalgia (100%), fatigue (50%), and paresthesia (20%). The median peak creatine kinase (CK) level was 4099 U/L (range 2,427-17250 U/L). Acute kidney injury (AKI) complicated the course in one patient (10%). All patients immediately discontinued the herbal intake and received supportive treatment including aggressive hydration and urine alkalinization. The median hospital stay was 6 days. At the last follow-up, all patients survived, with complete resolution of muscular symptoms and recovery of renal function. The causal relationship between rhabdomyolysis and <i>O. vulgatum</i> was assessed as \"probable\" for all ten patients according to the WHO-UMC scale.</p><p><strong>Conclusion: </strong>This is the first case series indicating an association between <i>O. vulgatum</i> consumption and severe rhabdomyolysis. Clinicians and the public should be aware of this risk and should avoid excessive or unconventional use. A detailed history of herbal medicine use is recommended for patients presenting with unexplained myalgia and elevated CK levels.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"17 ","pages":"1807082"},"PeriodicalIF":4.8,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836528","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":"Correction: Edaravone plays protective effects on LPS-induced microglia by switching M1/M2 phenotypes and regulating NLRP3 inflammasome activation.","authors":"Jiping Li, Xinping Dai, Liuyi Zhou, Xinxiu Li, Dongxiao Pan","doi":"10.3389/fphar.2026.1774570","DOIUrl":"https://doi.org/10.3389/fphar.2026.1774570","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fphar.2021.691773.].</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"17 ","pages":"1774570"},"PeriodicalIF":4.8,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836388","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":"Opioid analgesic use during pregnancy: a drug utilization cohort study in Catalonia.","authors":"Veerle Driessen, Lina Camacho-Arteaga, Maria Giner-Soriano, Lucía Bellas, Antonia Agustí","doi":"10.3389/fphar.2026.1804898","DOIUrl":"https://doi.org/10.3389/fphar.2026.1804898","url":null,"abstract":"<p><strong>Background: </strong>The increasing use of opioids during pregnancy and their potential adverse effects on fetal development have raised public health concerns. This study aimed to investigate the opioid prescribing patterns among pregnant women in Catalonia, Spain.</p><p><strong>Materials and methods: </strong>A retrospective drug-utilization study was conducted using the Information System for Research in Primary Care (SIDIAP) database, covering 75% of the Catalan population. Pregnancies in women aged 12-50 years between April 2011 and March 2020 were included. Opioid exposure was defined as at least one opioid prescription during pregnancy and was estimated through prevalence and cumulative incidence in pregnancy episodes and by trimester. We also examined pregnancy outcomes, exposure duration, and the use of non-opioid analgesics prior and concomitant to opioid therapy.</p><p><strong>Results: </strong>Among 41,398 pregnancies, 998 (2.41%) were exposed to prescribed opioids. Opioid prescribing increased over time, particularly since 2013 and mainly for non-cancer pain. Most exposures involved weak opioids (96.39%), with tramadol being the most frequently prescribed. Paracetamol use before or during opioid treatment was common, while NSAID use was less frequent. In over one-third of cases, opioid exposure exceeded 30 days, with even longer durations for those exposed to strong opioids.</p><p><strong>Conclusion: </strong>Our findings show a rise in opioid prescribing among pregnant women in Catalonia, primarily for non-cancer pain. Contradicting current guidelines, opioids were often prescribed without prior or concurrent NSAID use and with extended exposure durations. This underscores the need for pregnancy-specific pain management guidelines and stricter adherence to existing recommendations to minimize potential risks to the fetus.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"17 ","pages":"1804898"},"PeriodicalIF":4.8,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13144071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836409","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":"Tetracycline reprograms inflammatory and regenerative signaling pathways in human keratinocytes exposed to <i>Loxosceles</i> spider venoms and sphingomyelinases.","authors":"Bruna Fernandes Pinto, Priscila Hess Lopes, Carlos Eduardo Madureira Trufen, Ana Tung Ching Ching, Inácio de Loiola Meirelles Junqueira de Azevedo, Milton Yutaka Nishiyama-Jr, Denise V Tambourgi","doi":"10.3389/fphar.2026.1783681","DOIUrl":"https://doi.org/10.3389/fphar.2026.1783681","url":null,"abstract":"<p><strong>Introduction: </strong><i>Loxosceles</i> spider envenomation, or loxoscelism, constitutes the most severe form of araneism and frequently progresses to dermonecrosis with significant tissue damage. The key venom component, sphingomyelinase D (SMase D), drives both local and systemic effects through its structurally distinct Class I and II isoforms, each differing in toxicity. The current therapies provide limited benefit and, once necrosis is established, interventions are primarily supportive, underscoring the need for more effective pharmacological options. While tetracyclines have emerged as promising modulators of cutaneous loxoscelism in animal models, beyond their antimicrobial properties and owing to their ability to inhibit matrix metalloproteinases, the molecular mechanisms underlying their protective effects remain poorly defined.</p><p><strong>Methods: </strong>This study aimed to elucidate the transcriptomic landscape of tetracycline-associated protection in human keratinocytes in response to <i>Loxosceles</i> venoms and SMase D Class I and II isoforms.</p><p><strong>Results: </strong>Using transcriptomic profiling, we show that tetracycline upregulates <i>SOX2</i> and <i>SOX18</i> while downregulating IL1RL1 in keratinocytes exposed to <i>Loxosceles</i> venoms and SMases D. These regulatory changes are associated with reduced IL-1-mediated inflammation and activate pathways related to cell migration, epidermal morphogenesis, and tissue regeneration. Gene Ontology enrichment supported these findings, linking tetracycline treatment to biological processes of proliferation, wound closure, and repair. Furthermore, tetracycline attenuates SMase D-induced expression of pro-inflammatory and proteolytic mediators, shifting gene expression patterns toward profiles compatible with tissue homeostasis.</p><p><strong>Conclusion: </strong>Collectively, these transcriptomic findings, together with our previous functional studies, support a mechanistic framework in which tetracycline mitigates venom-induced pathology and highlight its potential as a therapeutic candidate for cutaneous loxoscelism and warrants targeted functional validation in future studies.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"17 ","pages":"1783681"},"PeriodicalIF":4.8,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835373","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":"Modulation of programmed cell death by botanical drugs in Alzheimer's disease: a review from a traditional Chinese medicine perspective.","authors":"Boyu Li, Ziheng Cui, Yanji Xu, Meihua Xu","doi":"10.3389/fphar.2026.1811185","DOIUrl":"https://doi.org/10.3389/fphar.2026.1811185","url":null,"abstract":"<p><p>Alzheimer's disease (AD) involves dysregulation of programmed cell death (PCD) pathways, such as apoptosis, ferroptosis, autophagy, and pyroptosis. Current therapeutic options are limited, prompting interest in multi-target regulators such as metabolites derived from traditional Chinese medicine (TCM) botanical drugs. This systematic review critically evaluates recent studies on TCM-derived metabolites that modulate PCD in AD models. We identify key limitations: many metabolites are pan-assay interference metabolites (PAINS) with questionable pharmacological relevance; preclinical models inadequately recapitulate sporadic AD; and translational challenges persist in bioavailability and brain targeting. Future research requires orthogonal validation, improved delivery systems, and stage-specific strategies. This review provides a critical foundation for the development of TCM-inspired therapies for AD.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"17 ","pages":"1811185"},"PeriodicalIF":4.8,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836257","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}