Front Pharmacol [JOURNAL]
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200 papers
HER2-mutated lung squamous cell carcinoma responding to trastuzumab deruxtecan followed by pyrotinib: a Case Report.
Liu L, Zhang JW, Fu Y … +3 more , Chen J, Zhou JY, Ma CY
Front Pharmacol · 2026 · PMID 42394988 · Full text
INTRODUCTION: HER2 (ERBB2) alterations are recognized oncogenic drivers in non-small cell lung cancer, but they are uncommon and poorly characterized in lung squamous cell carcinoma (LSCC). CASE PRESENTATION: We report a...
INTRODUCTION: HER2 (ERBB2) alterations are recognized oncogenic drivers in non-small cell lung cancer, but they are uncommon and poorly characterized in lung squamous cell carcinoma (LSCC). CASE PRESENTATION: We report a patient with initially resected stage IA2 LSCC who subsequently developed metastatic pulmonary recurrence. Molecular profiling of the resected tumor revealed an ERBB2 exon 20 p. G776V (p.Gly776Val) mutation, MET amplification, and copy-number deletions involving CDKN2A/B, MTAP, and TERT. Postoperative systemic therapy was administered as an individualized off-guideline strategy after multidisciplinary discussion. Following pulmonary recurrence and subsequent progression on platinum-based therapy, trastuzumab deruxtecan (T-DXd) achieved clinically meaningful disease control but was discontinued because of suspected drug-associated interstitial lung disease/pneumonitis complicated by pulmonary infection. Pyrotinib was subsequently administered and achieved disease control despite gastrointestinal intolerance. After further disease progression and clinical improvement of the prior pulmonary event, reduced-dose T-DXd was cautiously reintroduced, resulting in an additional radiologic response and approximately 7 months of disease control. The later clinical course was complicated by suspected treatment-associated cardiac dysfunction and terminal respiratory deterioration related to progressive pulmonary disease and infection. CONCLUSION: This case suggests that ERBB2 activating mutations may represent potentially actionable alterations in selected patients with recurrent LSCC. Comprehensive genomic profiling may identify rare therapeutic opportunities in this histologic subtype. However, individualized off-guideline treatment, HER2-directed therapy sequencing, and T-DXd rechallenge after pulmonary toxicity require cautious multidisciplinary risk-benefit assessment.
Awareness, attitudes, and self-reported clinical management of antimicrobial-associated neurocognitive adverse effects among healthcare providers in Saudi Arabia.
Prabahar K, Alghamdi W, Alshehri H … +5 more , Alharbi S, Alshareef H, Alatawi Y, Zaitone S, Hamdan AME
Front Pharmacol · 2026 · PMID 42394987 · Full text
BACKGROUND: Antimicrobials are among the most frequently prescribed medications worldwide, yet their neurocognitive adverse effects remain underrecognized. The adverse effects range from mild symptoms to serious effects...
BACKGROUND: Antimicrobials are among the most frequently prescribed medications worldwide, yet their neurocognitive adverse effects remain underrecognized. The adverse effects range from mild symptoms to serious effects and unrecognized adverse effects may influence prescribing behaviors and inappropriate continuation or discontinuation of antimicrobial therapy. Evidence on healthcare providers' awareness, attitudes, and self-reported clinical management regarding neurocognitive risks is limited, especially in Saudi Arabia. This study aimed to evaluate healthcare providers' awareness, attitudes, and self-reported clinical management of antimicrobial-associated neurocognitive adverse effects in Saudi Arabia. METHODS: A cross-sectional survey was conducted among healthcare providers in primary, secondary, and tertiary healthcare settings. A structured, self-administered questionnaire assessed awareness, attitudes, and self-reported clinical management related to neurocognitive adverse effects. Descriptive statistics and inferential analyses (Chi-square/Fisher's exact tests) were performed. RESULTS: Among 370 participants, 41.1% reported encountering neurological or cognitive symptoms during antimicrobial therapy, most commonly confusion and agitation. Fluoroquinolones were most frequently implicated (61.9%). High awareness was observed in 31.1%, while 27.0% demonstrated low awareness. Positive attitudes toward considering neurocognitive risks were reported by 74.6%. Most providers (94.1%) reported appropriate clinical management of suspected neurocognitive adverse effects, but only 46.2% reported consistent documentation. Physicians demonstrated significantly higher awareness, more positive attitudes, and more appropriate management than other professions (p < 0.05). CONCLUSION: Important gaps in awareness and documentation of neurocognitive adverse effects persist among healthcare providers. Strengthening multidisciplinary education, integrating neurocognitive safety into antimicrobial stewardship programs, and improving reporting systems are essential to enhance patient safety.
Low-dose dasatinib in second-line therapy or beyond for the treatment of chronic-phase chronic myeloid leukemia: a real-world cohort study.
Chen Y, Wang H, Cheng F … +1 more , Li W
Front Pharmacol · 2026 · PMID 42394986 · Full text
BACKGROUND: Dasatinib is a favorable option for patients with chronic-phase chronic myeloid leukemia (CML-CP) who have an inadequate response, treatment intolerance, or are attempting treatment-free remission (TFR). Dasa...
BACKGROUND: Dasatinib is a favorable option for patients with chronic-phase chronic myeloid leukemia (CML-CP) who have an inadequate response, treatment intolerance, or are attempting treatment-free remission (TFR). Dasatinib dose reduction is a strategy to improve tolerability while maintaining efficacy in first-line settings or patients with a stable molecular response. However, whether low-dose dasatinib is safe and effective in second-line or later setting for patients with CML-CP remains unclear. METHODS: We conducted a retrospective analysis of 53 patients with CML-CP who switched to low-dose dasatinib due to inadequate molecular response (n = 37), treatment intolerance (n = 13), or to re-induce a deeper molecular response (n = 3). RESULTS: Among the 37 patients who had not achieved major molecular response (MMR) before switching, 10 patients (27.0%) attained MMR, 12 patients (32.4%) achieved deep molecular response (DMR/MR4), and 11 patients (29.7%) reached molecular response 4.5 (MR4.5) following low-dose dasatinib therapy. Notably, 81.8% of patients with only baseline MMR improved to MR4 or MR4.5 after switching to low-dose dasatinib. One patient lost MR4 while receiving dasatinib at 50 mg/day and subsequently switched to nilotinib. All three patients who were switched to re-induce deeper molecular responses successfully re-attained MR4.5 after switching to low-dose dasatinib. Adverse events resolved in all 13 patients who switched due to prior TKI intolerance, and no worsening grade 2 or more adverse events were observed. CONCLUSION: Our findings suggest that low-dose dasatinib for selected patients with CML-CP in second-line therapy or beyond may be safe and effective under close monitoring. Nevertheless, multicenter prospective clinical trials are needed to validate the efficacy and safety of low-dose dasatinib therapy in second-line treatment settings or beyond in CML.
Natural products reshape osteosarcoma cell fate: promoting cell death.
Yan B, Chang J, Zhao P … +3 more , Sun X, Guo S, Yang Y
Front Pharmacol · 2026 · PMID 42394985 · Full text
Osteosarcoma is the most prevalent primary malignant bone tumor in children and adolescents. Despite advancements in adjuvant chemotherapy and surgical techniques, the overall survival rate of osteosarcoma patients remai...
Osteosarcoma is the most prevalent primary malignant bone tumor in children and adolescents. Despite advancements in adjuvant chemotherapy and surgical techniques, the overall survival rate of osteosarcoma patients remains suboptimal, particularly in cases of metastatic or recurrent disease. Programmed cell death (PCD), a highly regulated process that includes apoptosis, autophagy, ferroptosis, pyroptosis, and necroptosis, plays a pivotal role in determining cellular fate (survival and death). In osteosarcoma, PCD dysregulation enables malignant cells to evade cell death signals, thereby accelerating tumor development. Natural products derived from various medicinal plants and dietary components exhibit promising potential for osteosarcoma treatment by regulating PCD through different mechanisms. With advantages such as low cost, minimal side effects, and wide availability, natural products have attracted considerable attention for translational research. This review systematically synthesizes current knowledge on PCD subtypes in osteosarcoma and elucidates the molecular mechanisms by which natural products regulate PCD to inhibit the development of osteosarcoma. By integrating these insights, we aim to offer novel perspectives for developing targeted therapeutic strategies and improving clinical outcomes in osteosarcoma patients.
Houtt. extract containing isoquercitrin reduces airway inflammation in mice with allergic asthma.
Guimarães CC, Borges MC, Fabro AT … +8 more , Cardoso PH, Acunha T, Faccioli LH, Pereira SIV, Contini SHT, França SC, Carmona F, Pereira AMS
Front Pharmacol · 2026 · PMID 42394984 · Full text
BACKGROUND: Houtt. (Lamiaceae) has traditionally been used to treat respiratory disorders, including cough and dyspnea. The aim of this study was to investigate the therapeutic potential of a standardized hydroalcoholic...
BACKGROUND: Houtt. (Lamiaceae) has traditionally been used to treat respiratory disorders, including cough and dyspnea. The aim of this study was to investigate the therapeutic potential of a standardized hydroalcoholic extract from the aerial parts of in an model of allergic asthma. METHODS: Balb/c mice were sensitized and challenged with ovalbumin (OVA) and then treated intraperitoneally with (at doses of 100, 200, or 400 mg/kg), dexamethasone (at a dose of 2 mg/kg), or saline for seven consecutive days during intranasal OVA challenges. Bronchial hyperresponsiveness, lung cytokine levels (IL-4, IL-5, IL-10, and IFN-γ), inflammatory cells in bronchoalveolar lavage fluid (BAL), lung inflammation, and mucus production were evaluated. The chemical profile of the extract was determined by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). RESULTS: significantly reduced bronchial hyperresponsiveness, eosinophil infiltration, peribronchial inflammation and mucus secretion at all tested doses. The 200 mg/kg dose reduced IL-4 and IL-10 levels, and the 400 mg/kg dose decreased IL-5 and IL-10 levels. Isoquercitrin was identified as the major constituent of the extract. CONCLUSION: These findings support the traditional use of and suggest its potential as an anti-inflammatory and immunomodulatory agent for treating allergic asthma.
Enhancing diabetes treatment by targeted nucleic acid and drug delivery using cell-penetrating peptides, peptide nucleic acids, and receptor targeting.
Zaric BL, Khodahemmati S, Zafirovic SS … +1 more , Isenovic ER
Front Pharmacol · 2026 · PMID 42394983 · Full text
Precise regulation of gene expression and drug delivery is required to maximize therapeutic efficacy and minimize adverse side effects. Several studies indicate a potential role for targeted gene and drug delivery in the...
Precise regulation of gene expression and drug delivery is required to maximize therapeutic efficacy and minimize adverse side effects. Several studies indicate a potential role for targeted gene and drug delivery in the precision therapy of type 2 diabetes and other diseases. This review summarizes recent knowledge on the cell-penetrating function and membrane-crossing roles of cell-penetrating peptides, the application of peptide nucleic acids for gene modulation, and the precise delivery of genetic material and drugs to insulin signaling and other relevant β-cell and type 2 diabetes-related genes through antibody/receptor targeting. The rationale for peptide nucleic acid-based delivery platforms is then reviewed, including their neutral charge, strong hybridization capacity, versatility, and nuclease resistance, These properties enable precise modulation of gene expression in relevant tissues for the treatment of type 2 diabetes. Finally, the review also focuses on the delivery approaches of antibody- and receptor-mediated strategies. These strategies use either whole antibodies or engineered antibody fragments and are typically used to deliver treatments to β-cells and to cells involved in metabolism.
Risk factors for Post-PCI cardiovascular events in coronary artery disease patients treated with clopidogrel combined with aspirin.
Zhou J, Wang QS
Front Pharmacol · 2026 · PMID 42394982 · Full text
BACKGROUND: Cytochrome P450 family two subfamily C member 19 (CYP2C19) loss-of-function (LOF) variants may influence clopidogrel response after percutaneous coronary intervention (PCI), but their prognostic relevance wit...
BACKGROUND: Cytochrome P450 family two subfamily C member 19 (CYP2C19) loss-of-function (LOF) variants may influence clopidogrel response after percutaneous coronary intervention (PCI), but their prognostic relevance within combined clinical and procedural risk assessment remains incompletely defined. This study aimed to evaluate the association between CYP2C19 functional phenotype and major adverse cardiac and cerebrovascular events (MACCE) in coronary artery disease (CAD) patients receiving clopidogrel-based dual antiplatelet therapy (DAPT) after PCI. METHOD: This retrospective observational study included 280 consecutive CAD patients who underwent PCI with stent implantation and received aspirin plus clopidogrel. The primary endpoint was time to first MACCE. Multivariable Cox proportional hazards regression was the primary analysis, with logistic regression as a secondary supportive analysis. Kaplan-Meier analysis, subgroup interaction analyses, and sensitivity analyses were performed. RESULTS: During a median follow-up of 32.0 months, 52 patients experienced MACCE (18.6%). In the primary Cox model, older age, diabetes mellitus, lower estimated glomerular filtration rate, lower left ventricular ejection fraction, greater total stent length, post-procedural Thrombolysis In Myocardial Infarction (MI) flow <3, and CYP2C19 LOF phenotype were associated with time to first MACCE. CYP2C19 LOF remained significant after adjustment (adjusted hazard ratio 1.74, 95% confidence interval 1.10-2.75; P = 0.018). Kaplan-Meier analysis showed lower MACCE-free survival in LOF carriers than in non-LOF patients (log-rank P = 0.007). Interaction analyses suggested stronger LOF-associated risk patterns in acute coronary syndrome and complex PCI subgroups. CONCLUSION: In clopidogrel-treated CAD patients after PCI, CYP2C19 LOF phenotype was associated with MACCE in a clinical-procedural risk framework. These findings support further prospective validation of integrated genotype-informed post-PCI risk stratification.
Efficacy and safety of incretin-based therapies in patients with type 2 diabetes mellitus: a network meta-analysis based on clinical trials.
Wu X, Yang Y, Cui X … +2 more , Li X, Li Y
Front Pharmacol · 2026 · PMID 42394981 · Full text
OBJECTIVES: This study systematically assessed the efficacy and safety of 15 incretin-based therapies (IBTs) for type 2 diabetes mellitus (T2DM), including mono- (GLP-1RA), dual- (GIP/GLP-1RA or GLP-1/GCGR), and triple-...
OBJECTIVES: This study systematically assessed the efficacy and safety of 15 incretin-based therapies (IBTs) for type 2 diabetes mellitus (T2DM), including mono- (GLP-1RA), dual- (GIP/GLP-1RA or GLP-1/GCGR), and triple- (GIP/GLP-1/GCGR) receptor agonists, and explored how dosage and treatment duration affect clinical outcomes to support individualized treatment decisions. METHODS: A systematic review and Bayesian network meta-analysis were performed following PRISMA 2020 and PRISMA-NMA guidelines (PROSPERO: CRD420251152746). We searched MEDLINE, Cochrane Library, and Embase up to 1 August 2025, for randomized controlled trials (RCTs). Study selection, data extraction, risk-of-bias assessment (Cochrane RoB 2.0) and CINeMA framework were conducted. Analyses included SUCRA ranking, sensitivity, subgroup, and meta-regression in R Studio 4.4.3. RESULTS: 102 RCTs (98,693 T2DM patients) with low overall bias were included. IBTs were superior to placebo in glycemic control (tirzepatide, orforglipron, semaglutide best), weight loss (retatrutide best), lipid, blood pressure, cardiorenal, and insulin function improvement. The most common adverse events were mild, transient gastrointestinal reactions, and the risk of hypoglycemia was low. Higher doses improved efficacy but increased adverse events; 45 mg orforglipron balanced benefits and tolerability. Optimal duration and combination efficacy varied by agent. CONCLUSION: IBTs provide comprehensive benefits in T2DM. Efficacy and safety differ across agents, doses, durations, and combinations, supporting individualized therapy. Long-term high-quality RCTs are needed. Cardiovascular protection may stem from synergistic improvements in lipids, blood pressure, renal function, and insulin sensitivity. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD420251152746.
Phytochemical properties of Roxb. improve sperm quality, testosterone levels, and testicular histology in male mice.
Suriani NL, Ho TS, Alzahrani NS … +5 more , Alghamdi MM, Suprapta DN, Suarsana IN, Hamidah E, Suarni NMR
Front Pharmacol · 2026 · PMID 42394980 · Full text
BACKGROUND: Medicinal plants used in traditional systems of medicine are a valuable source of bioactive compounds with therapeutic potential against oxidative stress-related disorders, including male infertility. Roxb....
BACKGROUND: Medicinal plants used in traditional systems of medicine are a valuable source of bioactive compounds with therapeutic potential against oxidative stress-related disorders, including male infertility. Roxb. is an ethnomedicinally important species known for its antioxidant, anti-inflammatory, and aphrodisiac properties; however, its effects on male reproductive function remain insufficiently characterized. PURPOSE: This study aimed to evaluate the metabolites composition and dose-dependent effects of extract on sperm quality, testicular histology, and testosterone levels in male mice. METHODS: A total of 24 male mice were divided into four groups (n = 6) using a completely randomized design. The ethanol extract of rhizomes was dissolved in distilled water and administered at designated doses: 364 mg/kg BW (P1), 728 mg/kg BW (P2), and 1,092 mg/kg BW (P3). Plant metabolites were quantified via spectrophotometry and GC-MS analysis. Serum testosterone levels were measured using ELISA, while testicular histology and morphometric parameters were assessed using hematoxylin-eosin staining and microscopic imaging. RESULTS: Analysis revealed the presence of flavonoids, phenolics, tannins, and alkaloids. The P3 treatment significantly improved sperm concentration by 155% compared to the control. However, the P2 treatment yielded the highest percentage of viable spermatozoa (85.78%), motility (39.28%), and normal morphology (84.67%), alongside enhanced seminiferous tubule structure and spermatogenic cell density. These effects are attributed to the ROS-scavenging activity of phytochemicals, which preserve cellular morphology and support spermatogenesis. Serum testosterone levels increased in a dose-dependent manner, correlating with Leydig cell proliferation. Notably, while the moderate dose (P2) resulted in optimal reproductive outcomes, the highest dose (P3) showed a decline in sperm quality and histological alterations. CONCLUSION: enhances male reproductive functions, supporting its traditional use as a fertility-enhancing medicinal plant. However, its effects are dose-dependent, with optimal benefits observed at moderate concentrations and potential toxicity at higher doses. These findings provide novel preclinical evidence for the use of in managing male infertility and establish a pharmacological basis for future clinical investigations.
Comparative real-world safety profiles of caspofungin, micafungin, and anidulafungin: a disproportionality analysis based on FAERS and VigiAccess databases.
Chen J, Chen C, Lin X … +4 more , Yan J, Zheng Y, Chen P, Li J
Front Pharmacol · 2026 · PMID 42394979 · Full text
BACKGROUND: Caspofungin, micafungin, and anidulafungin are three commonly used echinocandins recommended for the treatment of invasive candidiasis. This study aimed to comprehensively evaluate the safety profiles of thes...
BACKGROUND: Caspofungin, micafungin, and anidulafungin are three commonly used echinocandins recommended for the treatment of invasive candidiasis. This study aimed to comprehensively evaluate the safety profiles of these three agents to assist clinicians in making appropriate therapeutic decisions. METHODS: A cross-sectional pharmacovigilance study based on the FDA Adverse Event Reporting System (FAERS) database was performed. Adverse event (AE) reports were collected from January 2004 to March 2025. The reporting odds ratio, proportional reporting ratio, and Bayesian confidence propagation neural network were used to identify, assess, and compare AE signals of the three echinocandins. Data from the VigiAccess database were used for external validation. RESULTS: A total of 2343, 2338, and 406 cases associated with caspofungin, micafungin, and anidulafungin, respectively, were extracted from the FAERS database. Caspofungin exhibited a tendency toward higher reporting frequencies of hepatobiliary disorders and skin and subcutaneous tissue disorders compared with micafungin and anidulafungin. Hepatobiliary signals observed for anidulafungin should be interpreted cautiously, as they may reflect confounding by indication related to preferential use in patients with underlying hepatic dysfunction rather than direct drug toxicity. A range of AEs that were not highlighted in the labels were identified. Logistic regression analyses indicated that skin and subcutaneous tissue disorders associated with caspofungin or micafungin were significantly associated with hospitalization reporting. Supplementary PT-level analyses further identified several clinically relevant AEs associated with hospitalization, including drug reaction with eosinophilia and systemic symptoms for caspofungin, renal failure for micafungin, and hepatic failure for anidulafungin. Higher disproportionality signals related to caspofungin and micafungin were observed in patients aged≥65 years and females. Additionally, the sensitivity analyses demonstrated that this study possessed good robustness. The median time-to-onset of AEs was significantly longer for caspofungin at 4 days (IQR: 0-11 days) than for micafungin at 2 days (IQR: 0-8 days, < 0.001) and anidulafungin at 1 day (IQR: 0-10 days, = 0.001). The results in VigiAccess were broadly consistent with FAERS findings. CONCLUSION: This study provides a comparative pharmacovigilance overview of the safety profiles of three echinocandins using FAERS and VigiAccess data. Further prospective studies are needed to validate these observations.
The tryptanthrin derivative g2 suppresses tongue squamous cell carcinoma via PI3K/AKT/P53 cathway modulation: evidence from and studies.
Miao J, Zhang S, Wang M … +3 more , Li Z, Lv N, Sun M
Front Pharmacol · 2026 · PMID 42394978 · Full text
INTRODUCTION: Tongue squamous cell carcinoma (TSCC) is a prevalent and aggressive oral malignancy with a poor prognosis and limited treatment options, underscoring the need for novel therapeutic agents. Tryptanthrin deri...
INTRODUCTION: Tongue squamous cell carcinoma (TSCC) is a prevalent and aggressive oral malignancy with a poor prognosis and limited treatment options, underscoring the need for novel therapeutic agents. Tryptanthrin derivatives have shown promising anticancer potential across various cancers. This study aimed to evaluate the antitumor efficacy and elucidate the mechanism of action of a novel tryptanthrin derivative, , against TSCC. METHODS: The cytotoxic effect of was initially screened against CAL-27 and SCC9 TSCC cells using a CCK-8 assay among 36 derivatives. Its half-maximal inhibitory concentration (IC) was determined. A comprehensive set of assays, including scratch wound-healing, Transwell migration, flow cytometry for apoptosis and cell cycle analysis, transcriptome sequencing, and western blotting, were employed to assess its effects on cell migration, apoptosis, cycle progression, and underlying signaling pathways. For validation, a xenograft model was established by implanting CAL-27 cells into nude mice, which were then treated with (10 or 20 mg/kg) via intratumoral injection. Tumor growth was monitored, and harvested tissues were analyzed by western blotting. RESULTS AND DISCUSSION: demonstrated the most potent cytotoxicity, with IC values of 1.997 μM for CAL-27 and 2.134 μM for SCC9 cells. It significantly inhibited cell migration and invasion, induced apoptosis, and caused S-phase cell cycle arrest in a dose-dependent manner. Transcriptome sequencing and western blotting analyses revealed that activated the PI3K/AKT/P53 signaling pathway, evidenced by the downregulation of PI3K/AKT and upregulation of P53. , treatment markedly suppressed tumor growth without observable systemic toxicity, and consistent modulation of the PI3K/AKT/P53 pathway was confirmed in tumor tissues. These findings collectively demonstrate that the tryptanthrin derivative exerts significant anti-TSCC effects both and , primarily through the modulation of the PI3K/AKT/P53 pathway, highlighting its potential as a promising therapeutic candidate. Further studies are warranted to explore its full mechanistic spectrum and efficacy in broader models.
Periostin in allergic rhinitis: from pathogenic mediator to predictive biomarker and therapeutic target.
Wang H, Zhang Q, Hu M … +2 more , Shao J, Wang G
Front Pharmacol · 2026 · PMID 42394977 · Full text
Allergic rhinitis (AR) is a common disease around the world, mediated by type 2 immune responses, and some patients don't respond well to current standard treatments. This shows AR isn't a single type of disease but a co...
Allergic rhinitis (AR) is a common disease around the world, mediated by type 2 immune responses, and some patients don't respond well to current standard treatments. This shows AR isn't a single type of disease but a complex syndrome caused by different internal body mechanisms. Periostin is a key matrix protein sitting downstream of the interleukin-4 (IL-4) and interleukin-13 (IL-13) pathways, connecting type 2 immune responses and nasal mucosal tissue remodeling. This article explains periostin's many roles in AR: it breaks down the epithelial barrier, makes eosinophils gather, and causes fibrosis, and these things form a never-ending "inflammation-repair" vicious cycle. In clinical use, periostin levels in different biological samples matter-they relate to how severe the disease is and show how patients respond to glucocorticoids and biologics. Targeting periostin directly might offer new ways to help with hard-to-treat tissue remodeling. Based on these findings, we suggest a way to classify AR using periostin levels, which aims to guide personalized treatment in the future and help AR diagnosis and therapy become true precision medicine.
Choline supplementation protects against sepsis-induced lung injury, potentially through suppression of Prtn3-associated monocyte activation.
Xu LM, Chen WC, Sun ZD … +6 more , Zhang LH, Liu YB, Luo XT, Chen Y, Lin L, He HF
Front Pharmacol · 2026 · PMID 42394976 · Full text
OBJECTIVE: Choline supplementation has been implicated in the regulation of inflammation and immune responses. This study aimed to investigate the protective effects of choline supplementation in sepsis-induced lung inju...
OBJECTIVE: Choline supplementation has been implicated in the regulation of inflammation and immune responses. This study aimed to investigate the protective effects of choline supplementation in sepsis-induced lung injury (SLI) and to elucidate the underlying mechanisms. METHODS: SLI was induced in mice via cecal ligation and puncture (CLP). Serum choline levels were measured, and choline supplementation effects were evaluated . Integrated transcriptomic and proteomic analyses identified potential targets and pathways. Public single-cell RNA sequencing data determined the cellular distribution of candidate genes. assays in THP-1 cells were performed to validate the role of key targets. RESULTS: Compared with Sham controls, SLI mice exhibited significantly decreased serum choline levels. The SLI mouse model exhibited typical pathological features, including pulmonary hemorrhage, interstitial edema, alveolar wall thickening, elevated inflammatory cytokines, and increased lung injury scores, all of which were significantly alleviated by choline supplementation. Multi-omics analyses identified Prtn3 as a potential target associated with the protective effects of choline. Single-cell analysis suggested that Prtn3 is predominantly expressed in monocyte/macrophage populations. , choline treatment attenuated LPS-induced inflammatory responses and chemotactic activity in THP-1 cells, accompanied by reduced expression of IL-1β, IL-6, TNF-α, Prtn3 and NF-κB pathway proteins. Prtn3 overexpression partially reversed the inhibitory effects of choline on cytokine production, monocyte migration, and NF-κB pathway activation. Conversely, pharmacological inhibition of Prtn3 by sivelestat suppressed inflammatory cytokine expression and attenuated NF-κB signaling under LPS-stimulated conditions. CONCLUSION: Choline supplementation protects against SLI by suppressing monocyte inflammatory activation, at least in part through inhibition of the Prtn3-dependent NF-κB signaling pathway. These findings suggest that targeting the choline-Prtn3-NF-κB axis may represent a potential therapeutic strategy for sepsis-associated lung injury.
The effectiveness and safety of commercial Chinese polyherbal preparation in treating infantile anorexia: a systematic review and Bayesian network meta-analysis.
Liu R, Liu J, Li L
Front Pharmacol · 2026 · PMID 42394975 · Full text
OBJECTIVE: Commercial Chinese polyherbal preparations (CCPPs) are increasingly used for infantile anorexia (IA), but comparative effectiveness and safety differences among them remain unclear. This Bayesian network meta-...
OBJECTIVE: Commercial Chinese polyherbal preparations (CCPPs) are increasingly used for infantile anorexia (IA), but comparative effectiveness and safety differences among them remain unclear. This Bayesian network meta-analysis compares various CCPPs for IA to inform clinical practice. METHODS: We systematically searched CNKI, Wanfang, VIP, China Biology Medicine, PubMed, Web of Science, Embase, and Cochrane Library for RCTs on CCPPs for IA up to 9 April 2024. Study quality was assessed using the Cochrane RoB tool. Primary outcomes were overall effective rate, weight change, hemoglobin (Hb) levels, and adverse reactions. This research implemented Bayesian network meta-regression to ascertain the impact of different CCPPs and durations of treatment on the effectiveness and safety to treat IA. RESULTS: 141 RCTs (n = 16,963 patients; 49 CCPPs) were included. For overall effective rate, Huaji Oral Solution (HJKFY), Jianpi Pills + Reference Drug (JPW + RD), and Erkangning (EKN) showed significant superiority vs. control (all RR > 1.54, P < 0.05). Regarding weight change, Erpixing Granules (EPXKL) and Xiaoer Fufang Jineijin Chewable Tablets + RD (XEFFJNJJJP + RD) demonstrated significant benefits (MD = 2.26 and 2.10, P < 0.05 for XEFFJNJJJP + RD). For Hb levels, Jianbaoling Granules (JBLKL), Erbao Granules + RD (EBKL + RD), and Shenqu Xiaoshi Oral Solution + RD (SQXSKFY + RD) showed significant advantages (all MD > 10.72, P < 0.05). CCPPs exhibited a favorable safety profile, with mostly mild adverse reactions. CONCLUSION: CCPPs are significantly more effective and safer than control treatments for IA. Different CCPPs excelled on specific outcomes: HJKFY for overall efficacy, EPXKL for weight gain, and JBLKL for Hb improvement. These findings require confirmation via larger, high-quality, multi-center RCTs. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD42024535550.
Reversal of ABCG2-mediated MDR by VEGFR3 inhibitor (S)-SAR131675.
Chen X, Xu J, Li R … +5 more , Dong XD, Li YD, Teng QX, Wang Z, Chen ZS
Front Pharmacol · 2026 · PMID 42394974 · Full text
Multidrug resistance (MDR) remains a major challenge in cancer treatment, as it is a significant factor contributing to chemotherapy failure and cancer recurrence. Among various resistance mechanisms, the overexpression...
Multidrug resistance (MDR) remains a major challenge in cancer treatment, as it is a significant factor contributing to chemotherapy failure and cancer recurrence. Among various resistance mechanisms, the overexpression of the breast cancer resistance protein (BCRP/ABCG2) has been identified as a cause of MDR in multiple cancers, including breast cancer, lung cancer, and colon cancer (S)-SAR131675 is the S-enantiomer of SAR131675 (HY-15458), which significantly and selectively suppresses the Vascular Endothelial Growth Factor Receptor 3 (VEGFR3). In this research (S)-SAR131675 shows the ability to overcome the ABCG2-mediated MDR in both the non-small cell lung cancer cell line NCI-H460 and its ABCG2-overexpressing cell line NCI-H460/TPT10, as well as the colorectal cancer cell line S1 and its ABCG2-overexpressing cell line S1-M1-80. Through several experiments, we demonstrate that (S)-SAR131675 targets the efflux function of ABCG2, resulting in an increased intracellular concentration of substrates of ABCG2, including mitoxantrone and topotecan. Additionally, this resensitizing effect did not affect the overall protein expression or subcellular localization of ABCG2 in the ABCG2-overexpressing cell lines. In summary (S)-SAR131675 can overcome ABCG2-mediated MDR by directly suppressing the drug efflux function, providing a promising basis for the further development of cancer treatments associated with MDR in the future.
Differential recovery of ventricular repolarization and hemodynamics following bupivacaine and ropivacaine intoxication: the impact of lipophilicity on lipid emulsion efficacy.
Rodríguez-Rodríguez L, Orallo-Martínez J, Fernández-López I … +7 more , Vázquez E, García-Ramos S, Quintela O, Bravo B, Alvarez-Zaballos S, Anadón-Baselga MJ, Zaballos M
Front Pharmacol · 2026 · PMID 42394973 · Full text
INTRODUCTION: Local anesthetic systemic toxicity (LAST) causes significant ventricular repolarization disturbances. While intravenous lipid emulsion (ILE) is the standard treatment, the factors governing the simultaneous...
INTRODUCTION: Local anesthetic systemic toxicity (LAST) causes significant ventricular repolarization disturbances. While intravenous lipid emulsion (ILE) is the standard treatment, the factors governing the simultaneous recovery of electrical and mechanical functions remain unclear. We evaluated ILE efficacy in reversing repolarization alterations and hemodynamic collapse induced by clinically equipotent doses of bupivacaine and ropivacaine. METHODS: Twelve swine were randomized to receive a toxic bolus of bupivacaine (4 mg/kg) or ropivacaine (5 mg/kg). The primary outcome was the Area Under the Curve (AUC) of the corrected T-peak to T-end interval (Tp-TeC) during the recovery phase. Secondary outcomes included QTc and mean blood pressure (MBP) AUCs. Analysis was divided into a toxicity induction phase (0-3 min) and a recovery phase (3-25 min) to integrate the magnitude and duration of the alterations. RESULTS: Both anesthetics significantly impaired repolarization, with no differences in total toxic load during the initial phase ( > 0.05). Following ILE, a distinct pharmacological divergence occurred. Electrical recovery was significantly more effective in the bupivacaine group, with lower recovery AUC values for the primary outcome (Tp-TeC, = 0.002) and QTc ( = 0.004). Conversely, hemodynamic rescue was more robust following ropivacaine intoxication (higher MBP recovery AUC, = 0.025). Recovery of QRS duration and sinus cycle length was similar between groups. CONCLUSION: Our findings demonstrate a distinct pharmacological divergence in lipid resuscitation therapy. Bupivacaine's higher lipophilicity (Log D) enhances electrical recovery via a more efficient "lipid shuttle" effect on ion channels, while ropivacaine's lower intrinsic cardiotoxicity allows for a more resilient mechanical recovery. These results suggest that electrical and mechanical rescue are governed by different rules dictated by the anesthetic's physicochemical properties.
Durable responses to long-term selumetinib in Chinese pediatric NF1 patients with inoperable plexiform neurofibromas.
Zhang X, Sui W, Zheng H … +2 more , Chen J, Yuan X
Front Pharmacol · 2026 · PMID 42394972 · Full text
BACKGROUND: This study provides the first long-term efficacy and safety data of selumetinib in Chinese pediatric patients with inoperable symptomatic plexiform neurofibromas (PN) associated with neurofibromatosis type 1...
BACKGROUND: This study provides the first long-term efficacy and safety data of selumetinib in Chinese pediatric patients with inoperable symptomatic plexiform neurofibromas (PN) associated with neurofibromatosis type 1 (NF1). METHODS: In this single-center Phase I clinical trial(NCT04590235), we enrolled children with NF1-related PN aged 3 to <18 years and treated them with selumetinib at a dose of 25 mg/m twice daily in 28-day cycles until disease progression or intolerance. The study consisted of a predefined treatment phase, with a final data cutoff (DCO) on August 15, 2023, followed by an extended follow-up period with a latest DCO on March 1, 2025. Tumor response was assessed by volumetric MRI using Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) criteria. Safety was evaluated per CTCAE v5.0. Patient-reported outcomes included pain, health-related quality of life (HRQoL), and exploratory growth and dermatologic assessments. Prior PK data have been reported. RESULTS: A total of 16 children were enrolled (median age 11 years; range 4-16) . At the final DCO, the median follow-up duration was 25 cycles (range, 24-33). With extended follow-up at the latest DCO, patients received treatment for a median of 45 cycles (range, 20-52). The objective response rate (ORR) remained 81.3% (95% CI, 54.4%-96.0%) at both the final and latest DCOs, demonstrating durable tumor responses over long-term treatment. At Cycle 42 (predefined assessment timepoint at the latest DCO), the median best percentage reduction in target PN volume was 47.3%. All patients experienced at least one adverse event (AE), while 12 of 16 patients (75.0%) experienced at least one treatment-related adverse event (TRAE). Most TRAEs were Grade 1-2 and consistent with the known safety profile of selumetinib. No Grade ≥3 TRAEs were observed. Treatment was associated with improvements in pain and HRQoL scores. Exploratory analyses suggested increased growth velocity and reduced café-au-lait macule pigmentation in prepubertal patients. CONCLUSIONS: Long-term selumetinib treatment in Chinese pediatric patients with NF1-related PN resulted in durable tumor responses and sustained pain improvement. No new safety signals were identified, although ongoing monitoring of known adverse events remains warranted. TRIAL REGISTRATION: NCT04590235, registered at ClinicalTrials.gov, URL: https://clinicaltrials.gov/study/NCT04590235?term=NCT04590235&rank=1.
Harpagophytum procumbens in musculoskeletal disorders: current evidence and comparison with NSAIDs.
Hong JY, Lee J, Kim H … +6 more , Kim H, Jeon WJ, Yeo C, Lee YJ, Go HY, Ha IH
Front Pharmacol · 2026 · PMID 42394971 · Full text
Harpagophytum procumbens (HP), commonly known as Devil's Claw, is a traditional medicinal plant widely used for musculoskeletal pain and inflammatory conditions. Interest in HP has increased because long-term use of non-...
Harpagophytum procumbens (HP), commonly known as Devil's Claw, is a traditional medicinal plant widely used for musculoskeletal pain and inflammatory conditions. Interest in HP has increased because long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) may be limited by gastrointestinal, cardiovascular, and renal adverse effects. This structured narrative review summarizes current evidence regarding the pharmacological mechanisms, clinical efficacy, safety, pharmacokinetics, regulatory status, and comparative role of HP relative to NSAIDs. Preclinical studies suggest that HP and its constituents, particularly harpagoside, may modulate inflammatory pathways including cyclooxygenase-2, nuclear factor-κB, pro-inflammatory cytokines, and oxidative stress signaling. However, these mechanistic findings represent indirect evidence and should be interpreted cautiously in relation to clinical outcomes. Clinical studies, mainly in osteoarthritis and low back pain, suggest that selected HP preparations may provide symptomatic benefit in some patients. However, the clinical evidence base remains limited by small sample sizes, heterogeneous formulations, variable dosages, short follow-up durations, and a scarcity of high-quality head-to-head randomized trials against NSAIDs. In contrast, NSAIDs are supported by a substantially broader and higher-certainty evidence base for pain relief and functional improvement. Available safety data suggest that HP is generally well tolerated, although product quality, standardization, and long-term safety data remain variable across jurisdictions. Current evidence does not support positioning HP as a general replacement for NSAIDs. Rather, HP may be considered as a complementary or selective option for some patients, particularly where NSAID intolerance or long-term safety concerns exist. Further large-scale, rigorously designed randomized trials using standardized formulations are required.
Safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of STSA-1002, recombinant anti-human C5a fully human monoclonal antibody, in a randomized, first-in-human phase I study in healthy adults.
Fang Y, Wang X, Qi L … +14 more , Tong Y, Wei Y, Li Z, Liu C, Liu J, Cheng X, Liu X, Liu F, Li Y, Li Y, Liu L, Sun M, Wang Y, Wang X
Front Pharmacol · 2026 · PMID 42394970 · Full text
STSA-1002 is a fully human monoclonal antibody targeting C5a, which plays a critical role in the pathogenesis of virus-induced acute respiratory distress syndrome ARDS (v-ARDS). We investigated safety, pharmacokinetics,...
STSA-1002 is a fully human monoclonal antibody targeting C5a, which plays a critical role in the pathogenesis of virus-induced acute respiratory distress syndrome ARDS (v-ARDS). We investigated safety, pharmacokinetics, pharmacodynamics, and anti-drug antibodies of increasing multiple intravenous doses of STSA-1002 in healthy adults. studies, STSA-1002 was a high-affinity, selective anti-human C5a monoclonal antibody blocking C5a-mediated reactive oxygen species (ROS) production. Building on the published preclinical results, a randomized, double-blind, placebo-controlled, dose-escalation study was done at a Phase I unit in China. A total of 60 adverse events (AEs) were reported. In the STSA-1002 group (n = 20), 47 AEs occurred in 18 participants (90.0%), corresponding to a mean of 2.6 AEs per participant. In the placebo group (n = 6), 13 AEs occurred in all 6 participants (100%), corresponding to a mean of 2.2 AEs per participant. Grade 2 or greater study drug-related adverse events included neutrophil count decreased, white blood cell count decreased, and aminotransferase increased. C and AUC increased in an approximately dose-proportional manner. After the first dose, the mean concentration of free C5a in all dose groups was suppressed to below the lower limit of quantification. This suppression was maintained in all health volunteers until D42 (5 mg/kg) and D56 (10 mg/kg and 20 mg/kg) after multiple doses. Besides, STSA-1002 could downregulate the levels of myeloperoxidase (MPO), neutrophil elastase (NE), and proteinase 3 (PR3). Overall, multiple infusions of STSA-1002 up to 20 mg/kg appear to be safe and well tolerated in healthy participants in China. The safety, PK, and PD data support the continued evaluation of STSA-1002 in larger Phase II studies. https://clinicaltrials.gov/, ID NCT05497635.
Use of analgesics during pregnancy: patterns of use and knowledge of medication safety among women in Serbia.
Maletin N, Kusturin M, Denda N … +2 more , Rašković A, Kusturica MP
Front Pharmacol · 2026 · PMID 42394969 · Full text
BACKGROUND: Analgesics are commonly used during pregnancy, and their safe use depends on the type of drug, timing of exposure, and appropriateness of use. This study assessed patterns of analgesic use before and during p...
BACKGROUND: Analgesics are commonly used during pregnancy, and their safe use depends on the type of drug, timing of exposure, and appropriateness of use. This study assessed patterns of analgesic use before and during pregnancy and evaluated women's knowledge and perceptions regarding analgesic safety during pregnancy in Serbia. METHODS: A cross-sectional study was conducted using an electronically distributed, self-administered questionnaire adapted from a previously published instrument. The survey included socio-demographic and reproductive characteristics, patterns of analgesic use, and a 19-item knowledge inventory. Knowledge scores were categorized as low (<10 points) or high (≥10 points). Descriptive statistics and logistic regression were used for analysis. RESULTS: A total of 538 women participated. Overall, 51.7% reported analgesic use during pregnancy, and among these, 50.7% reported use during the first trimester. Paracetamol was the most commonly used analgesic during pregnancy (93.9%). Analgesic use without prior consultation was reported by 32.0% of women who used analgesics during pregnancy. Before pregnancy, 83.1% reported analgesic use. Although 69.3% reported having received information about adverse effects, important uncertainty remained regarding NSAID classification and safety. Overall, 65.1% of respondents had a low level of knowledge. Health-professional background was strongly associated with a high level of knowledge (adjusted OR 12.468, 95% CI 7.502-20.724; p < 0.001). CONCLUSION: Analgesic use during pregnancy was common, including use without prior consultation. Despite recognizing paracetamol as the preferred analgesic, many women had limited knowledge regarding analgesic safety, particularly NSAIDs, in pregnancy. These findings support the need for improved counselling and targeted education on medication safety during pregnancy.
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