Frontiers In Pharmacology[JOURNAL]
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200 papers
Mechanism of zedoary turmeric oil multi-components targeting S100A14 to reprogram astrocytes against tumor brain metastasis.
Wang XY, Liu JR, Yao ZY … +11 more , Yang X, Cai ZH, Wang MR, Wang WX, Huang QZ, Zhang HX, Liu ZQ, Feng Q, Xie CJ, Zhang RR, Qiao LJ
Front Pharmacol · 2026 · PMID 42375602 · Full text
BACKGROUND: Zedoary Turmeric Oil (ZTO) is an active extract derived from the traditional Chinese medicine Ezhu, which is conventionally used to promote blood circulation, remove blood stasis, and relieve pain. Neverthele...
BACKGROUND: Zedoary Turmeric Oil (ZTO) is an active extract derived from the traditional Chinese medicine Ezhu, which is conventionally used to promote blood circulation, remove blood stasis, and relieve pain. Nevertheless, the therapeutic potential and underlying molecular mechanism of ZTO against tumor brain metastasis (BrM) remain poorly elucidated. METHODS: The anti-BrM efficacy of ZTO was firstly assessed through S100A14-overexpress tuomor cells intracarotid injection BrM mice model. Concurrently, GC-MS analysis, computer simulation, along with experiments were employed to comprehensively investigate the mechanism by which ZTO targets S100A14 to suppress BrM. RESULTS: Our study first identified ZTO as a promising candidate against S100A14-driven BrM. In mouse model, high-dose ZTO (200 mg/kg) significantly reduced brain BLI from 21465.73 ± 20757.36 to 1417.37 ± 2878.98 in 4T1-S100A14 breast cancer. ZTO also exhibited concentration-dependent BrM inhibition effects in LLC S100A14 lung cancer. ZTO remodeled the BrM microenvironment by regulating GFAP astrocytes via the NF-κB pathway, inhibiting migration, invasion, EMT, and MMPs. Additionally, ZTO dose-dependently suppressed the secretion of IL-6, CCL2, and CXCL1, thereby reducing recruitment of both P-MDSCs and M-MDSCs. Multi-analysis revealed that Curdione, Curzerene, Germacrone, Curcumenol, and Curcumenone directly bind S100A14, enhancing its thermal stability and resistance to protease hydrolysis. CETSA results confirmed thermal stabilization: Curzerene ΔTm = +22 °C, Germacrone ΔTm = +14.2 °C, Curdione ΔTm = +17.7 °C. CONCLUSION: ZTO exhibited potent anti-BrM efficacy and the mechanism involved multiple components synergistically targeting S100A14 to reprogram astrocytes, which in turn reduced the secretion of pro-inflammatory factors, thereby inhibiting the recruitment of MDSCs and reshaping the immunosuppressive microenvironment of the brain. Collectively, our study provides the first experimental evidence that the multiple bioactive components in ZTO act synergistically to target S100A14, offering a promising new direction for the development of anti-BrM therapeutic strategies.
Esketamine improves postoperative sleep quality in thoracic surgery patients with preoperative sleep disturbance: a randomized controlled trial.
Wang X, Wang H, Luo H
Front Pharmacol · 2026 · PMID 42375601 · Full text
OBJECTIVE: To investigate the effect of multiple intraoperative subanesthetic doses of esketamine on postoperative sleep quality in non-cardiac thoracic surgery patients with preoperative sleep disturbance. METHODS: This...
OBJECTIVE: To investigate the effect of multiple intraoperative subanesthetic doses of esketamine on postoperative sleep quality in non-cardiac thoracic surgery patients with preoperative sleep disturbance. METHODS: This was a prospective single-center, double-blind placebo-randomized controlled trial of 100 patients undergoing elective non-cardiac thoracic surgery under general anesthesia with preoperative sleep disturbance who were given 0.25 mg/kg esketamine at induction of anesthesia and cutaneous suture compared with placebo to prevent the occurrence of postoperative sleep disturbance. Primary outcomes were the incidence of postoperative sleep disturbance on postoperative day 1, as assessed by Numeric Rating Scale, Athens Insomnia Scale and RCSQ. Secondary outcomes included the incidence of postoperative sleep disturbance on postoperative day 3 and 5,sleep duration, proportion of deep sleep, proportion of rapid eye movement sleep, postoperative pain score, postoperative anxiety score and depression score, intraoperative hemodynamic parameters and blood biomarkers (IL-6,IL-10, and brain-derived neurotrophic factor). RESULT: A total of 100 patients were randomized to the control group and the esketamine group. The incidence of postoperative sleep disturbance in the esketamine group was significantly lower than in the control group on POD 1 (50%vs 82%; odds ratio [OR], 0.2 [95% CI, 0.1-0.5]; P = 0.001) and POD 3 (22%vs 42%; OR, 0.4 [95% CI, 0.2-0.9]; P = 0.032). And there were significant differences in sleep duration, proportion of deep sleep and proportion of REM sleep (Based on exploratory Fitbit-derived estimates) on postoperative day 1 and 3. By POD 5, the difference was no longer statistically significant. Postoperative pain scores at rest and during movement were significantly lower in the esketamine group immediately after surgery and on postoperative day 1 compared with the control group, with no significant differences on postoperative days 3 and 5. Anxiety and depression scores (HADS) were significantly lower in the esketamine group on postoperative days 1, 3, and 5. Intraoperative hemodynamic parameters demonstrated higher systolic and mean arterial pressures in the esketamine group during anesthesia induction (T2) and lower pressures and heart rate during extubation (T6), indicating attenuated hypotension at induction and blunted stress response at extubation. Intraoperative sufentanil consumption was significantly lower in the esketamine group. Compared with preoperative levels, serum IL-6 concentrations increased in both groups on POD 1, 3, and 5; however, the esketamine group exhibited lower IL-6 levels than the control group on POD one and POD 3, with the difference attenuating by POD 5. Serum IL-10 levels were elevated on POD 1, 3, and five in the esketamine group and were significantly higher than those in the control group at all three time points. Serum BDNF concentrations were increased relative to baseline on POD 1, 3, and five in both groups, and were consistently higher in the esketamine group than in the control group across all postoperative assessments. Subgroup analyses demonstrated that intraoperative esketamine consistently reduced the incidence of postoperative sleep disturbance across predefined subgroups stratified by age, sex, PSQI score, and ASA classification, with no significant interaction effects observed. CONCLUSION: Multiple intraoperative infusion of 0.25 mg/kg esketamine can effectively improve the postoperative sleep quality of non-cardiac thoracic surgery patients with preoperative sleep disturbance, reduce the incidence of postoperative sleep disturbance, reduce the use of opioids, reduce the occurrence of intraoperative hypotension events, reduce the stress response during extubation, maintain the stability of intraoperative hemodynamics, reduce postoperative pain, and relieve adverse emotions. Moreover, esketamine decreased the level of the pro-inflammatory cytokine IL-6, increased the level of the anti-inflammatory cytokine IL-10, attenuated the postoperative inflammatory response, and promoted the release of BDNF. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/bin/project/edit?pid=248681, identifier ChiCTR2500096036.
Complement-targeted therapies for transplant-associated thrombotic microangiopathy: recent advances.
Tokura T, Motomura S
Front Pharmacol · 2026 · PMID 42371577 · Full text
Transplant-associated thrombotic microangiopathy (TA-TMA) is a life-threatening complication of hematopoietic stem cell transplantation in which systemic complement activation induces endothelial injury, leading to micro...
Transplant-associated thrombotic microangiopathy (TA-TMA) is a life-threatening complication of hematopoietic stem cell transplantation in which systemic complement activation induces endothelial injury, leading to microangiopathic hemolytic anemia, thrombocytopenia, and organ dysfunction. TA-TMA often progresses rapidly and has historically been associated with high mortality. Over the last decade, increasing recognition of complement activation as a central driver of TA-TMA has shifted management from largely empirical supportive care toward mechanism-based therapy. This review summarizes recent advances in complement-targeted therapies for TA-TMA and outlines key aspects of pathophysiology, risk factors, and monitoring that inform therapeutic decision-making. Earlier non-complement-directed therapies, including calcineurin inhibitor modification, plasma exchange, defibrotide, and rituximab, showed limited and inconsistent benefit. In contrast, complement-targeted therapies have advanced the treatment of TA-TMA. Prospective and large cohort data support the clinical activity of eculizumab (C5 inhibitor), with meaningful improvements in survival and organ recovery. Ravulizumab (long-acting C5 inhibitor) has shown encouraging phase 3 results, and narsoplimab (MASP-2 inhibitor), which became the first approved treatment for TA-TMA, has demonstrated promising outcomes, including activity in some patients previously exposed to C5 inhibition. In addition, newer agents targeting C5, C3, or factor B are expanding the therapeutic horizon for TA-TMA, although efficacy data are still limited for some of these therapies. Overall, complement-targeted therapies represent a therapeutic advance in TA-TMA, and ongoing prospective studies will be crucial to define optimal agent selection, sequencing, and integration into clinical practice.
Safety and efficacy of the MNK/VEGFR inhibitor JDB153 combined with the anti-PD-1 antibody serplulimab in patients with advanced pancreatic cancer refractory to standard treatment: a single-arm, phase Ib/II study protocol.
Zhu X, Wei H, Cao D … +1 more , Xu H
Front Pharmacol · 2026 · PMID 42371576 · Full text
INTRODUCTION: Pancreatic cancer remains a leading cause of death with poor prognosis. Current standard chemotherapies offer limited survival benefits, and no standard treatment exists for patients failing two lines of th...
INTRODUCTION: Pancreatic cancer remains a leading cause of death with poor prognosis. Current standard chemotherapies offer limited survival benefits, and no standard treatment exists for patients failing two lines of therapy. Preclinical evidence suggests that targeting MNK and VEGFR pathways can remodel the immunosuppressive tumor microenvironment and enhance immunotherapy efficacy. This study evaluates the safety and efficacy of JDB153 (an MNK/VEGFR inhibitor) combined with serplulimab (an anti-PD-L1 antibody) in refractory advanced pancreatic cancer. METHODS AND ANALYSIS: This is a prospective, open-label, single-center, phase Ib/II clinical trial (NCT07175389). It will enroll patients with advanced pancreatic adenocarcinoma who have progressed after standard therapies. The study follows a Simon's two-stage design. The initial phase will enroll 10 patients to test safety and preliminary efficacy. Patients will receive oral JDB153 and intravenous serplulimab. If at least one patient responds, the study will expand to a total of 32 patients. The primary endpoints are safety and ORR. Secondary endpoints include DFS, OS, and PFS. Safety will be graded using NCI-CTCAE version 5.0. Comprehensive biomarker analyses (PD-L1 expression, spatial immune profiling, next-generation sequencing, et al.) are integrated. DISCUSSION: Patients with advanced pancreatic cancer need effective options that are less toxic than chemotherapy. Immunotherapy alone often fails in this disease due to the immunosuppressive microenvironment. By combining MNK/VEGFR inhibition with PD-1 blockade, this study investigates a promising strategy to overcome immune resistance and establish a novel treatment paradigm for advanced pancreatic adenocarcinoma.
Knowledge, attitudes, and practices of community pharmacists regarding the management of diabetes during Ramadan in the Aseer Region, Saudi Arabia.
Khobrani M
Front Pharmacol · 2026 · PMID 42371575 · Full text
BACKGROUND: Fasting during Ramadan causes challenges for diabetes treatment, necessitating tailored counseling and adjustments for medication. Community pharmacists play a vital role in enhancing fasting safety, although...
BACKGROUND: Fasting during Ramadan causes challenges for diabetes treatment, necessitating tailored counseling and adjustments for medication. Community pharmacists play a vital role in enhancing fasting safety, although their readiness has not been well investigated in southern Saudi Arabia. This study aimed to evaluate community pharmacists' knowledge, attitudes, and practices (KAP) regarding diabetes management during Ramadan in the Aseer Region, and to identify perceived barriers and the need for additional training. METHODS: A descriptive cross-sectional study was performed from February to May 2025 with 301 licensed community pharmacists in the Aseer Region. Participants were recruited through professional pharmacy social media platforms and pharmacy communication groups commonly used within the region. Data were collected utilizing a previously validated self-administered questionnaire. Descriptive and inferential statistics were conducted using SPSS v26, with a significance level set at p < 0.05. Inferential findings were interpreted cautiously as subgroup comparisons. RESULTS: A total of 301 pharmacists participated. Knowledge of key safety measures during fasting was high, with 91.7% correctly identifying the blood glucose threshold (<60 mg/dL) requiring termination of fasting. Correct recognition of high-risk patients who should avoid fasting was reported for patients with recurrent hypoglycemia (88.7%) and elderly or unwell patients (87.4%). Knowledge related to medication regimen adjustment was lower, particularly in insulin dose modification, where 71.1% provided correct responses. In practice, more than 80% counseled patients on blood glucose monitoring and meal planning, while 63.8% addressed physical activity adjustments, and 68.1% counseled on medication regimen changes. The most frequently reported barriers were time constraints (85.7%), lack of updated training (84.7%), and inadequate counseling privacy (79.8%). Prior training was associated with higher knowledge and practice scores (p = 0.001). Pharmacists who attended training workshops demonstrated higher mean knowledge and practice scores than untrained pharmacists. CONCLUSION: Community pharmacists in the Aseer Region demonstrated generally adequate knowledge and positive attitudes regarding diabetes management during Ramadan, particularly in fasting-safety counseling and patient education. However, important gaps remained in advanced medication regimen adjustment practices, especially insulin dose modification, as well as participation in structured public education activities. Continuing professional development programs focused on Ramadan-specific diabetes management and interprofessional collaboration may improve pharmacist-led diabetes care during Ramadan.
Chemotherapy-induced peripheral neuropathy associated with docetaxel or nab-paclitaxel among patients with lung cancer: a prospective dual-center cohort study.
Liu Y, Li Y, Li X … +3 more , Zhang H, Liu X, Chen P
Front Pharmacol · 2026 · PMID 42367306 · Full text
OBJECTIVE: To compare the distinct clinical manifestations of chemotherapy-induced peripheral neuropathy (CIPN) in patients with different types of lung cancer treated with docetaxel or nab-paclitaxel, as well as to eval...
OBJECTIVE: To compare the distinct clinical manifestations of chemotherapy-induced peripheral neuropathy (CIPN) in patients with different types of lung cancer treated with docetaxel or nab-paclitaxel, as well as to evaluate the post-intervention symptom improvement following therapeutic management. METHODS: This prospective cohort study was conducted from September 2024 to August 2025 across two medical centers in China. Participants were lung cancer patients who had received treatment with either docetaxel or nab-paclitaxel. Chemotherapy-induced peripheral neuropathy (CIPN) was assessed using patient-reported outcomes from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-CIPN 20-item scale (EORTC QLQ-CIPN20). Multivariable regression models were adjusted for patient baseline characteristics, tumor status, and medication-related features. Evaluations were performed using overlap propensity score weighting. Data analysis was carried out from September 2025 to December 2025. RESULTS: Among the 850 participants, the mean (SD) age was 63.2 (10.5) years, with 385 patients (45.3%) receiving docetaxel and 465 patients (54.7%) receiving nab-paclitaxel. The docetaxel group primarily reported motor symptoms (e.g., leg weakness: 92 patients [34.2%]) and autonomic symptoms (e.g., blurred vision: 108 patients [40.1%]). In contrast, the nab-paclitaxel group predominantly reported sensory symptoms, such as numbness in the hands and feet (68 patients [25.3%]). The onset of patient-reported motor symptoms occurred earlier than sensory abnormalities, with median times of 2.3 weeks (95% CI, 1.3-5.4) in the docetaxel group and 0.8 weeks (95% CI, 0.6-1.2) in the nab-paclitaxel group. After adjustment using overlap propensity score weighting, patients in the docetaxel group had a lower risk of reported CIPN compared to those in the nab-paclitaxel group (HR, 0.65 [95% CI, 0.54-0.86]; = 0.015). Patients treated with docetaxel reported fewer sensory discomforts compared to those receiving nab-paclitaxel (HR, 0.61 [95% CI, 0.49-0.89]; = 0.001). However, the risk of reported motor symptoms (HR, 0.54 [95% CI, 0.44-0.69]; = 0.061) and/or autonomic symptoms (HR, 0.87 [95% CI, 0.62-1.22]; = 0.229) was not significantly lower in the docetaxel group than in the nab-paclitaxel group. CONCLUSION: In this cohort study of lung cancer patients, nab-paclitaxel was associated with more severe CIPN compared to docetaxel, regardless of patients' clinical characteristics. Multivariate analysis identified taxane type, number of prior treatment cycles, treatment phase, and the use of pregabalin for intervention as independent factors associated with patient-reported CIPN. These findings may contribute to early intervention and therapeutic decision-making for CIPN during taxane-based treatment of lung cancer.
Quercetin as a multifaceted neuroprotective agent against cerebral ischaemia-reperfusion injury: mechanisms and therapeutic potential.
Wang Y, Sheng H, Zhang Y … +3 more , Guo X, Wu E, Chen Y
Front Pharmacol · 2026 · PMID 42367305 · Full text
Cerebral ischaemia-reperfusion injury (CIRI) is a significant contributor to neurological dysfunction following ischemic stroke, involving multiple pathological mechanisms such as immune disorder, oxidative stress, infla...
Cerebral ischaemia-reperfusion injury (CIRI) is a significant contributor to neurological dysfunction following ischemic stroke, involving multiple pathological mechanisms such as immune disorder, oxidative stress, inflammatory response, and apoptosis. Quercetin, a flavonoid compound widely present in fruits, vegetables, and grains, exhibits multiple biological activities including antioxidant, anti-inflammatory, antiviral, and anti-tumor properties, and has demonstrated significant neuroprotective effects in CIRI models. Currently, systematic reviews on quercetin's antagonistic effects against CIRI are scarce, and its precise mechanism of action and clinical translational potential remain to be further explored. This article systematically reviews the multidimensional protective mechanisms of quercetin against CIRI, focusing on its action pathways in four dimensions: immune regulation, cell protection, organelle homeostasis maintenance, and blood-brain barrier (BBB) protection. Additionally, it discusses the clinical application prospects, safety, and existing challenges of quercetin, aiming to provide a theoretical basis for subsequent research on quercetin as a neuroprotective strategy and promote its clinical translation in the prevention and treatment of CIRI.
Editorial: New drugs and future challenges in drug metabolism and transport.
Đanić M, Oo C, Li X … +1 more , Mikov M
Front Pharmacol · 2026 · PMID 42367304 · Full text
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Curcumin protects high glucose-induced diabetic myocardial injury by regulating Nrf2 and PI3K/AKT pathways.
Xu Z, Qu Z, Wu X
Front Pharmacol · 2026 · PMID 42367303 · Full text
Hyperglycemia can lead to excessive production of reactive oxygen species (ROS), contributing to diabetes and its complications, such as diabetic cardiomyopathy (DCM). This study aims to elucidate the protective mechanis...
Hyperglycemia can lead to excessive production of reactive oxygen species (ROS), contributing to diabetes and its complications, such as diabetic cardiomyopathy (DCM). This study aims to elucidate the protective mechanisms of Curcumin (CUR) against hyperglycemia-induced cardiomyocyte injury. We constructed a high-glucose (HG) model using primary cardiomyocytes and determined the optimal concentration of CUR by assessing cell viability with the CCK-8 assay. Enzyme-linked assays were used to measure the activities of HO-1, T-SOD, and GSH-Px, investigating the antioxidant effects of the Nrf2 signaling pathway. Flow cytometry was employed to measure apoptosis and mitochondrial membrane potential (ΔΨm). Mitochondria were isolated from cardiomyocytes to examine cytosolic and mitochondrial cytochrome c (cytc) expression. Western blotting was used to analyze the expression levels of Nrf2, PI3K, AKT, Keap1, HO-1, Bcl-2, and Bax proteins. Our findings suggest that CUR enhanced the viability and antioxidant enzyme activity of primary cardiomyocytes under HG conditions, stabilized ΔΨm, reduced ROS production, and decreased apoptosis. Moreover, CUR alleviated HG-induced cardiomyocyte damage by upregulating Nrf2, PI3K, AKT, HO-1, and Bcl-2 expression, while downregulating Bax. These findings demonstrate that the protective effect of CUR against diabetic cardiac injury may be mediated through activation of the Nrf2 and PI3K/AKT signaling pathways and upregulation of antioxidant enzyme expression, aiming to provide a theoretical foundation for further research into the therapeutic application of CUR in DCM.
The real-world safety evaluation of the selective NaV1.8 inhibitor suzetrigine: disproportionality analysis and flexible empirical bayes signals from FAERS with external triangulation.
Lai K, Luo L, Zhang F … +4 more , Tan ESS, Gaurav A, Zheng J, Tan CK
Front Pharmacol · 2026 · PMID 42367302 · Full text
BACKGROUND: Suzetrigine (Journavx; VX-548), the first selective NaV1.8 voltage-gated sodium channel inhibitor approved by the FDA on 30 January 2025, represents a novel non-opioid option for moderate-to-severe acute pain...
BACKGROUND: Suzetrigine (Journavx; VX-548), the first selective NaV1.8 voltage-gated sodium channel inhibitor approved by the FDA on 30 January 2025, represents a novel non-opioid option for moderate-to-severe acute pain. Given its recent market entry and unique peripheral mechanism, comprehensive post-marketing safety surveillance is essential. OBJECTIVE: This study aimed to identify and characterize adverse event signals associated with suzetrigine in the FDA Adverse Event Reporting System (FAERS) using advanced disproportionality and comparator-referenced empirical Bayes (EB) methods, with external triangulation against published literature and WHO VigiBase data. METHODS: We analyzed FAERS reports through the first 8 months post-approval. Disproportionality metrics (ROR, PRR, IC) were supplemented by a comparator-referenced EB profiling approach that incorporated suzetrigine, acetaminophen, ibuprofen, and background "other drugs," generating 3,000 posterior draws per preferred term (PT). Signals with EB q05 > 2 and no comparator overlap were classified as suzetrigine-unique. High-priority PTs were triangulated with Phase II/III trial data, systematic reviews, case reports, and VigiBase report counts (February 2026). RESULTS: Of 19 prioritized PTs, 14 were suzetrigine-unique. Dominant clusters included sensory disturbances (paresthesia, burning sensation, skin burning sensation, hypoaesthesia; EB q05 11.43-31.16), musculoskeletal events (muscle spasms EB q05 31.15), and cutaneous reactions (pruritus, rash). These signals were mechanistically consistent with peripheral NaV1.8 blockade of nociceptors and pruriceptors. Literature and VigiBase data corroborated neurological/sensory and musculoskeletal signals; psychiatric signals (euphoric mood, abnormal dreams) lacked external support and were deprioritized. CONCLUSION: This real-world pharmacovigilance analysis identifies a distinct safety signature for suzetrigine, with neurological and sensory disturbances (e.g., paresthesia, burning sensation, skin burning sensation, hypoaesthesia) emerging as prominent signals not fully characterized in pre-approval trials, whereas musculoskeletal and cutaneous events largely align with labeled reactions. These hypothesis-generating findings highlight the need for focused post-marketing surveillance on neurological/sensory preferred terms through prospective cohort studies and Phase IV trials to quantify incidence, identify risk factors, and optimize risk-minimization strategies for this promising non-opioid analgesic.
Off-label prescribing in ophthalmology: a retrospective analysis.
Bucolo C, Gozzo L, Terranova L … +7 more , Badagliacca MR, Romano GL, Avitabile A, Russo A, Lazzara A, Drago F, Conti F
Front Pharmacol · 2026 · PMID 42367301 · Full text
Off-label practice is often needed in ophthalmology, due to the limited number of drugs approved to treat several ocular diseases and to manage challenging ocular surgeries. The aim was to analyze the off-label drug pres...
Off-label practice is often needed in ophthalmology, due to the limited number of drugs approved to treat several ocular diseases and to manage challenging ocular surgeries. The aim was to analyze the off-label drug prescriptions issued from January 2014 to December 2024 at the Department of Ophthalmology of the University Hospital of Catania (Italy). 233 off-label prescriptions, comprising 13 drugs, were delivered to treat 225 patients affected by ocular disorders. Results of the present study showed a raise of off-label prescriptions in 2015 and 2016 mainly due to mitomycin C use in trabeculectomy, representing 34.3% of the total off-label drug prescriptions in the reference period. After a decrease in 2017-2018, there was an increasing trend in the number of off-label issued prescriptions until 2024. The main contributors were anti-vascular endothelial growth factor (VEGF) drugs such as bevacizumab, ranibizumab and aflibercept, which represent 25.3%, 9.0% and 4.3% of off-label prescriptions, respectively. Additionally, 5-fluorouracil and dexamethasone were prescribed off-label, each representing 7.3% of the total off-label prescriptions, to mainly handle conjunctival carcinoma and various macular edema, respectively. Alteplase (6.9%), voriconazole (2.1%), verteporfin (1.3%), and foscarnet (0.9%), together with amphotericin B (0.4%), ganciclovir (0.4%), as well as rituximab (0.4%) were off-label prescribed to manage other specific ocular conditions. These results suggest that off-label practice is evolving in the field of ophthalmology. Collaboration among regulatory authorities, clinicians, marketing authorization holders, and patients is essential, in order to develop standardized, evidence-based international guidelines about off-label use, to improve outcome of patients with unmet medical needs.
Pharmacological safety and real-world efficacy of the potassium-competitive acid blocker fexuprazan in cardiovascular patients receiving antithrombotic therapy: a prospective cohort study (FEXGARD).
Hwang YM, Kim SJ, Yoo M
Front Pharmacol · 2026 · PMID 42367300 · Full text
BACKGROUND AND AIMS: Gastroesophageal reflux disease (GERD) is common in patients with CVD receiving long-term antithrombotic therapy, increasing gastrointestinal (GI) bleeding risk. Potassium-competitive acid blockers,...
BACKGROUND AND AIMS: Gastroesophageal reflux disease (GERD) is common in patients with CVD receiving long-term antithrombotic therapy, increasing gastrointestinal (GI) bleeding risk. Potassium-competitive acid blockers, such as fexuprazan, provide rapid and potent acid suppression; however, relevant evidence in this high-risk population is limited. This study evaluated the effects of fexuprazan on fasting serum gastrin levels, GERD symptoms, and bleeding outcomes in patients with CVD receiving antithrombotic agents. METHODS: In this prospective observational study conducted at a tertiary hospital, 400 patients receiving antiplatelet or anticoagulant therapy were administered fexuprazan. Fasting venous blood samples were collected at baseline and 6 months, and total serum gastrin levels were measured. GERD symptoms were assessed using the Frequency Scale for the Symptoms of GERD (FSSG). Secondary outcomes, including GI bleeding, other-site bleeding, and mortality, were recorded over 12 months. Subgroup analyses were performed according to antithrombotic regimen and age. RESULTS: Fexuprazan significantly increased fasting serum gastrin (152.1 ± 215.9 vs. 249.1 ± 210.3 pg/mL; p < 0.001) and improved FSSG total scores (16.3 ± 5.0 vs. 15.0 ± 6.0; p < 0.001). During the 12 months, two GI bleeding events (0.5%), 11 other-site bleeding events (2.8%), and no deaths occurred. Subgroup analyses revealed no significant differences between users of antiplatelet agents, warfarin, and non-vitamin K antagonist oral anticoagulants (NOACs). However, bleeding events occurred only in the NOAC group. Patients aged 70 years or older had a greater increase in gastrin than younger patients (+118.4 vs. +64.3 pg/mL; p = 0.025). CONCLUSION: Fexuprazan increased gastrin levels and improved GERD symptoms with few bleeding events in patients with CVD receiving antithrombotic therapy. This study provides clinical data on the safety and tolerability of fexuprazan in a high-risk cardiovascular population under long-term antithrombotic therapy. Elderly patients exhibited a greater increase in gastrin levels, warranting closer monitoring and further investigation.
Immune checkpoint inhibitor-related cardiotoxicity: a cellular pharmacology perspective on susceptibility and resistance.
Fang H, Guo B, Sun Y … +2 more , Jin W, Wang W
Front Pharmacol · 2026 · PMID 42367299 · Full text
Immune checkpoint inhibitors (ICIs) have reshaped the treatment landscape of cancer, yet their clinical benefit is accompanied by a distinct spectrum of immune-related toxicities. Among these, cardiotoxicity remains unco...
Immune checkpoint inhibitors (ICIs) have reshaped the treatment landscape of cancer, yet their clinical benefit is accompanied by a distinct spectrum of immune-related toxicities. Among these, cardiotoxicity remains uncommon but clinically consequential because it can evolve quickly, presents with marked heterogeneity, and may result in fulminant myocarditis, malignant arrhythmia, or hemodynamic collapse. Key mechanistic drivers include T-cell clonality directed against cardiac autoantigens (e.g., α-myosin heavy chain), cytokine amplification via JAK/STAT signaling, and innate immune recruitment. Recent work has shifted the field away from viewing ICI-related cardiotoxicity as a nonspecific inflammatory complication. Instead, available data support a model in which immune checkpoint blockade perturbs a broader tumor-host ecosystem and exposes organ-specific vulnerabilities within the heart. T-cell clonality, loss of peripheral tolerance, cytokine amplification, endothelial activation, stromal remodeling, and metabolic rewiring all appear to contribute, although their relative importance likely varies across patients. This review examines ICI-associated cardiotoxicity through the lens of cellular pharmacology. We focus on how checkpoint signaling sustains cardiac immune homeostasis, how susceptibility emerges from interactions between tumor-derived cues and host immune context, and why resistance to toxicity-directed therapy remains clinically relevant. We also discuss evolving biomarker strategies-including high-sensitivity troponins, cardiac MRI, and emerging immune-state markers-and mechanism-based interventions that may help reduce cardiac injury without fully negating antitumor efficacy. By framing cardiotoxicity as a context-dependent extension of systemic immune modulation rather than an isolated adverse event, we highlight unresolved questions that are central to the development of predictive biomarkers and more selective therapeutic strategies. Finally, we briefly note that structured nursing surveillance and multidisciplinary team coordination remain essential for translating mechanistic advances into improved bedside outcomes.
Microbiota-miR-101 interactions in obesity-associated colorectal cancer: from barrier dysfunction to precision therapeutic strategies.
Mishra SP, Jacobson R, Wang B … +5 more , Prajapati S, Sanberg P, Brechot C, Jain S, Yadav H
Front Pharmacol · 2026 · PMID 42367298 · Full text
Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide, with obesity recognized as a major modifiable risk factor. Obesity-associated CRC is characterized by systemic low-grad...
Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide, with obesity recognized as a major modifiable risk factor. Obesity-associated CRC is characterized by systemic low-grade inflammation, altered lipid metabolism, and gut microbial dysbiosis, all of which converge to create a pro-inflammatory niche. Emerging evidence implicates murine miR-101a/b, an ortholog of the human miR-101 family, as a key molecular mediator linking metabolic dysfunction, promoting inflammation, endotoxemia, and affecting epithelial homeostasis. Traditionally, the miR-101 family is considered a tumor suppressor by repressing oncogenes such as EZH2, MCL-1, and COX-2; miR-101a appears to exhibit a paradoxical microenvironment-modulating role in obese colon. Recent studies demonstrate that elevated dietary and microbiota-derived ethanolamine induces miR-101a overexpression in colonic epithelial cells. Mechanistically, miR-101a directly destabilizes the mRNA encoding the tight junction protein (ZO-1; TJP1), thereby impairing epithelial barrier integrity, increasing intestinal permeability, and promoting chronic inflammation. The chronic inflammation promotes epithelial proliferation, generates mutagenic reactive oxygen species, and activates pro-survival pathways such as STAT3 and AKT, collectively contributing to a tumor-permissive microenvironment that may support adenoma initiation and progression. The resulting chronic inflammatory milieu promotes epithelial stress, proliferative signaling, and accumulation of DNA damage, contributing to conditions that favor colorectal carcinogenesis. Importantly, this ethanolamine-miR-101a axis represents a novel mechanistic link between diet, microbiota, and cancer biology. Translationally, miR-101a holds promise as a biomarker of early barrier dysfunction and CRC risk, as detectable in tissue, serum, or fecal samples. Furthermore, microbiome-targeted interventions, dietary modifications, or direct inhibition of miR-101a may offer innovative therapeutic strategies. Collectively, these findings support the development of precision microbiome-miRNA-based approaches and highlight the importance of context-dependent miRNA regulation in obesity-associated CRC.
Gut microbiota regulation and Traditional Chinese Medicine syndrome differentiation in right- and left-sided colon cancer heterogeneity - A review.
Chen J, Zhao J, Zhang X … +1 more , Zhu H
Front Pharmacol · 2026 · PMID 42367297 · Full text
Colon cancer (CC) exhibits substantial heterogeneity between right-sided colon cancer (RCC) and left-sided colon cancer (LCC) in terms of embryological origin, molecular characteristics, immune microenvironment, and ther...
Colon cancer (CC) exhibits substantial heterogeneity between right-sided colon cancer (RCC) and left-sided colon cancer (LCC) in terms of embryological origin, molecular characteristics, immune microenvironment, and therapeutic response. Increasing evidence suggests that spatial heterogeneity of the gut microbiota may contribute to these site-specific differences through interactions with local immune, inflammatory, and metabolic microenvironments. Recent studies have also indicated that gut microbiota dysbiosis may participate in the progression, therapeutic response, and microenvironmental remodeling of CC. This review summarizes current evidence regarding the role of gut microbiota spatial heterogeneity in RCC and LCC, with particular emphasis on its potential associations with molecular features, immune regulation, and local metabolic alterations. Furthermore, we discuss recent advances in Traditional Chinese Medicine (TCM)-based interventions targeting the gut microbiota in CC, including potential links between common TCM syndromes, microbial dysbiosis, mucosal barrier dysfunction, and immune-inflammatory alterations. We also summarize the regulatory effects of representative botanical monomers and classical TCM formulas on microbial homeostasis and tumor-related microenvironmental changes. Importantly, this review does not aim to establish fixed correspondences between specific TCM syndromes and tumor location. Instead, gut microbiota heterogeneity may serve as a modern biological reference for understanding site-specific pathogenesis and guiding individualized TCM interventions in CC.
Intelligent CpG nanoplatforms for targeted cancer immunotherapy and immune remodeling.
Wang H, Zhang Y, Zhou M
Front Pharmacol · 2026 · PMID 42367296 · Full text
CpG oligonucleotides are potent immunoadjuvants that hold great promise for cancer immunotherapy, but their clinical use is limited by instability, off-target toxicity, and poor tumor targeting. Intelligent nanoplatform...
CpG oligonucleotides are potent immunoadjuvants that hold great promise for cancer immunotherapy, but their clinical use is limited by instability, off-target toxicity, and poor tumor targeting. Intelligent nanoplatforms offer effective solutions to these challenges by protecting CpG, improving delivery precision, and enabling on-demand cargo release. This review summarizes four major design strategies: biomimetic/biohybrid systems for targeted delivery, stimuli-responsive nanocarriers for controlled release, structural engineering for enhanced immune activation, and combinatorial therapy for systemic immune remodeling. These nanoplatforms not only improve CpG stability and tumor-targeting capability but also reshape the tumor immune microenvironment, convert "cold" tumors to "hot" phenotypes, and induce long-term immune memory. We highlight the design principles, action mechanisms, key advantages, and inherent limitations of current intelligent CpG-based nanosystems, aiming to advance the development and clinical translation of CpG nanotherapeutics for more effective and personalized cancer immunotherapy.
Tripterygium wilfordii Hook F accelerates CD4 T-cell recovery in ART-treated people living with HIV with incomplete immune reconstitution: a longitudinal cohort study.
Zheng L, Wang F, Song X … +6 more , Zhang L, Li Y, Lv W, Han Y, Cao W, Li T
Front Pharmacol · 2026 · PMID 42367295 · Full text
BACKGROUND: Incomplete immune reconstitution (INR) affects 9%-45% of ART-treated people living with HIV (PLWH) and is associated with increased morbidity and mortality. Chronic immune activation and inflammatory signalin...
BACKGROUND: Incomplete immune reconstitution (INR) affects 9%-45% of ART-treated people living with HIV (PLWH) and is associated with increased morbidity and mortality. Chronic immune activation and inflammatory signaling, particularly via the IP-10/CXCL10 pathway, are central to its pathogenesis. Whether Tripterygium wilfordii Hook F (TwHF), an immunomodulatory agent with established anti-inflammatory properties, can improve CD4 T-cell recovery in virologically suppressed PLWH with INR remains unclear. METHODS: We conducted a retrospective longitudinal cohort study at Peking Union Medical College Hospital. ART-treated, virologically suppressed PLWH with persistent CD4 T-cell counts <350 cells/μL were enrolled and classified into a TwHF group (n = 32, 10 mg three times daily) or a matched control group (n = 31). Participants were followed at five predefined time points spanning 12 months pre-treatment through 12 months post-discontinuation. Peripheral blood immunophenotyping assessed CD4 T-cell subsets (naïve and memory), CD4/CD8 ratio, and CD8 T-cell activation markers. A cytokine substudy measured IP-10/CXCL10 and eotaxin in 20 TwHF-treated and 14 control participants using multiplex immunoassay. Linear mixed-effects models were used for longitudinal analysis. RESULTS: TwHF was associated with a significantly accelerated rate of CD4 T-cell recovery compared with controls (group × time interaction coefficient 4.98, P < 0.001), with median counts of 254 vs. 222 cells/μL at 12 months (P = 0.011). This gain was attributable predominantly to memory CD4 T-cell expansion (216 vs. 164 cells/μL, P < 0.001), while naïve CD4 T-cell counts remained unchanged. The CD4/CD8 ratio improved more rapidly in the TwHF group (0.409 vs. 0.278 at month 12, P = 0.008). A clinically meaningful response (≥50 cells/μL/year) was achieved in 75.0% of TwHF-treated vs. 9.7% of controls. Within-person IP-10/CXCL10 levels declined significantly after TwHF treatment (median Δ -31.96 pg/mL, P = 0.017), particularly in good immunological responders. Immunological gains attenuated after treatment discontinuation, suggesting a treatment-dependent effect. Routine hematological and renal parameters remained within normal limits throughout follow-up, with no significant between-group differences. No serious adverse events were observed. CONCLUSION: TwHF accelerates CD4 T-cell reconstitution in virologically suppressed PLWH with INR, primarily through memory subset expansion and modulation of IP-10/CXCL10 inflammatory signaling, supporting its potential as an adjunctive immunomodulatory strategy.
Exploring how interprofessional forces shape population-health competencies for clinical pharmacy trainees.
Thomas D, Al-Shorbagy M, Jallo M … +3 more , Binoy S, Baker D, Zachariah S
Front Pharmacol · 2026 · PMID 42367294 · Full text
BACKGROUND: Interprofessional clinical training is increasingly recognized as essential for preparing pharmacy graduates to address both individual patient needs and broader population-health priorities. Yet how Doctor o...
BACKGROUND: Interprofessional clinical training is increasingly recognized as essential for preparing pharmacy graduates to address both individual patient needs and broader population-health priorities. Yet how Doctor of Pharmacy (PharmD) students actually develop population-health competencies within clinical environments remains poorly understood. METHODS: This qualitative research explored the learning frame with driving and restraining forces that shape population-health competence among final-year PharmD students during their clinical pharmacy training. Using semi-structured interviews were conducted with a clinical pharmacist, a medical doctor, a nurse, and three PharmD students at Thumbay University Hospital. ATLAS.ti software version 25 was used for data analysis. RESULTS: Data was collected from three professionals and seven pharmacy students. Thematic analysis following Braun and Clarke's six-phase approach generated 257 coded quotations and 17 themes. These themes were organized into three categories: learning frame themes, driving forces, and restraining forces. Findings show that students learn through iterative movement between population-to-patient and patient-to-population reasoning, supported by processes such as listening, observing, complementing team activities, validating clinical decisions, and implementing changes. Their development is shaped by driving forces including knowledge, compatibility, collaboration, integration, and trustworthiness, and restrained by limited knowledge, limited involvement, conflicting views, missing information, and unreliable performance. Together, these dynamics illustrate how interprofessional clinical environments can both foster and hinder the development of population-health competencies. CONCLUSION: This study highlights how population-health competence among PharmD trainees emerges through dynamic, interprofessional interactions that shape both their reasoning and clinical engagement. The interplay of driving and restraining forces within clinical environments reveals that supportive team processes can accelerate learning, while structural and relational barriers can impede it. Strengthening interprofessional integration and addressing these barriers may enhance the development of population-health competencies in future pharmacy training models.
Commentary: Awareness, use, attitudes, and implementation challenges of Bayesian dose prediction software in clinical practice: a multi-organizational survey.
Jiao Z, Shi J
Front Pharmacol · 2026 · PMID 42367293 · Full text
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Correction: Licochalcone A mitigates cisplatin-induced nephrotoxicity by inhibiting ferroptosis and mitochondrial dysfunction via the Nrf2/GPX4 axis.
Han M, Zhang F, Li M … +6 more , Zhang Q, Shen K, Zhang D, Xu H, Zhou F, Wang X
Front Pharmacol · 2026 · PMID 42367292 · Full text
[This corrects the article DOI: 10.3389/fphar.2026.1759824.].
[This corrects the article DOI: 10.3389/fphar.2026.1759824.].
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