Frontiers in Pharmacology最新文献

Background: Glioma is the most common primary brain tumor of the central nervous system and is associated with poor clinical outcomes, particularly in high-grade diease. The immune checkpoint protein B7-H3 (CD276) is significantly overexpressed in glioma and multiple other solid tumors, highlighting its potential as a diagnostic biomarker and therapeutic target. However, the availability of high-performance antibodies suitable for clinic in vitro diagnosis (IVD) applications remains limited.

Objective: This study aimed to develop a novel rabbit monoclonal antibody (clone 36H7) targeting human B7-H3, and to evaluate its suitability for clinical diagnostic use.

Methods: Rabbits were immunized with recombinant human B7-H3 protein, followed by monoclonal antibody generation and systematic screening. The resulting antibody was assessed for specificity, affinity and stability. Its performance was validated through Western blot, ELISA, surface plasmon resonance (SPR), flow cytometry, immunofluorescence, and immunohistochemistry (IHC).

Results: Clone 36H7 demonstrated high specificity and robust stability across multiple assay platforms. In IHC analysis of glioma samples (n = 206), B7-H3 positivity was detected in 97% of cases. In addition, B7-H3 expression was observed in 85.4% of vascular endothelial cells, supporting its strong detection capability in tumor-associated compartments. Tonsil tissue was established as a reliable quality control material to ensure assay consistency and reproducibility.

Conclusion: The rabbit monoclonal antibody 36H7 exhibits excellent specificity, stability and board applicability across analytical platforams, meeting key requirments for clinical diagnostic development targeting B7-H3 in glioma.

[This corrects the article DOI: 10.3389/fphar.2020.00951.].

Background: Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by cartilage destruction and functional impairment. Dysregulated autophagy plays a pivotal role in chondrocyte apoptosis and extracellular matrix (ECM) degradation. Pterostilbene (PT), a natural polyphenolic metabolite with high bioavailability, exhibits potent anti-inflammatory and antioxidant activities. However, its precise role in regulating autophagy during OA progression remains unclear.

Methods: Network analysis was employed to predict PT's potential molecular targets and signaling pathways. To experimentally evaluate the drug-target interaction, the cellular thermal shift assay (CETSA) was performed. Functional validation was subsequently conducted in vitro using IL-1β-stimulated C28/I2 chondrocytes and in vivo in a monosodium iodoacetate-induced OA rat model. The p53 inhibitor pifithrin-α was applied to verify the mechanistic dependency.

Results: Network analysis and molecular docking suggested p53 as a core target of PT. CETSA results supported the cellular target engagement of p53 by PT, showing that PT enhanced the thermal stability of p53 protein. In chondrocytes, PT mitigated IL-1β-induced ECM imbalance and apoptosis while enhancing Beclin1 expression and the LC3II/I ratio with reduced p62 accumulation. Mechanistically, PT promoted p53 nuclear accumulation, activated AMPK, and inhibited mTOR phosphorylation; these effects were attenuated by 3-methyladenine or pifithrin-α. In vivo, PT exhibited a dose-dependent chondroprotective effect, significantly reducing OARSI scores and restoring autophagy marker expression in cartilage tissue.

Conclusion: This study demonstrates that PT exerts chondroprotective effects by activating autophagy through the p53/AMPK/mTOR axis, supported by evidence of specific p53 target engagement. These findings unveil a previously unrecognized molecular mechanism and underscore the translational potential of PT as a promising disease-modifying metabolite for OA therapy.

Background: Ovarian cancer remains one of the most lethal gynecologic malignancies, characterized by high recurrence rates and chemoresistance. Recent advances suggest that neuroactive drugs such as lorazepam may exert off-target molecular effects beyond the central nervous system. However, their pharmacological relevance in tumor biology remains largely unexplored. This study aimed to identify and validate shared molecular targets of lorazepam and ovarian cancer, uncovering novel biomarkers and therapeutic mechanisms.

Methods: Potential lorazepam targets were retrieved from the CTD, STITCH, and SwissTargetPrediction databases and cross-referenced with ovarian cancer-related genes from GeneCards. Bioinformatic analyses were conducted, including target screening, protein-protein interaction network construction, Lasso-Cox modeling, and functional enrichment. We further performed immune infiltration profiling, single-cell and spatial transcriptomics analyses, followed by experimental validation using qPCR, CCK-8, colony formation, wound-healing, and flow cytometry assays.

Results: Fifty-one overlapping genes were identified between lorazepam and ovarian cancer, with PTK2 emerging as a central hub gene. PTK2 overexpression was significantly associated with poor prognosis, enhanced immune activation, stromal remodeling, and metabolic reprogramming. Spatial transcriptomics revealed PTK2 enrichment in malignant and fibroblast-rich regions. Functional assays confirmed that stable PTK2 knockdown inhibited proliferation, colony formation, and migration while promoting apoptosis in ovarian cancer cells.

Conclusion: Our findings suggest that PTK2 may act as a putative oncogenic mediator and potential pharmacological link between lorazepam signaling and ovarian cancer progression. PTK2 functions as a biomarker and druggable target that integrates tumor growth, immune modulation, and metabolic adaptation. Targeting PTK2 may provide a promising therapeutic strategy for precision oncology and rational drug repurposing.

Background: Systematically evaluate the effects of Kang'ai Injection (KAI) combined with platinum-based chemotherapy on immune function, clinical efficacy, and safety in patients with advanced non-small cell lung cancer.

Materials and methods: Relevant literature published from the inception of each database through September 2025 will be identified through systematic searches of Chinese and English electronic databases. Randomized controlled trials (RCTs) evaluating Kang'ai injection combined with chemotherapy for advanced non-small cell lung cancer will be screened against predefined inclusion and exclusion criteria. Two investigators will independently perform data extraction and quality assessment. Meta-analyses will be conducted using RevMan 5.3 and Stata 18.0 software. Publication bias will be assessed using funnel plots and Egger's test, while the robustness of findings will be examined through trial sequential analysis (TSA). The quality of evidence for critical outcomes will be evaluated using the GRADE approach.

Results: A total of 14 randomized controlled trials involving 1,214 patients were included. The meta-analysis demonstrated that compared with chemotherapy alone, KAI combined with chemotherapy significantly improved the objective response rate and enhanced immune function parameters, including increased CD3⁺ and CD4⁺ T-cell counts, elevated CD4⁺/CD8⁺ ratio, and higher natural killer cell percentage, while reducing CD8⁺ T-cell percentage. The combination therapy group also showed superior outcomes in reducing tumor marker and vascular endothelial growth factor levels compared to the chemotherapy-alone group. Furthermore, combination treatment significantly reduced the incidence of chemotherapy-related adverse reactions including leukopenia, myelosuppression, nausea and vomiting, and gastrointestinal reactions.

Conclusion: As an adjunctive therapy, KAI can enhance immune function (low-quality evidence), improve the objective response rate to chemotherapy (moderate-quality evidence), and alleviate chemotherapy-related toxicities (predominantly moderate-quality evidence) in patients with advanced NSCLC, providing an evidence-based reference for comprehensive clinical management.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251168090.

Background: Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by a lipid overload-induced pathological cascade featuring hepatocyte injury, inflammation, and progressive fibrosis. This study aims to systematically investigate the role of EMMPRIN in MASH progression, and to elucidate its mechanisms in reprogramming the hepatic metabolic microenvironment.

Methods: Murine models induced by methionine-choline -deficient diet, hepatocyte-specific EMMPRIN overexpression and knockout mice models were used to evaluate EMMPRIN' roles in steatohepatitis. Parallel in vitro studies were conducted in corresponding cellular models. Proteomic sequencing, mass spectrometry, co-immunoprecipitation, Western blotting, quantitative PCR, and immunofluorescence were employed to identify downstream targets and characterize ubiquitination modifications.

Results: EMMPRIN overexpression significantly exacerbated MASH phenotypes, including hepatic steatosis, inflammatory infiltration, and collagen deposition. Conversely, EMMPRIN knockout conferred substantial protection against these pathological changes both in vivo and in vitro. Mechanistically, EMMPRIN downregulated UBA52 expression, resulting in reduction in the free ubiquitin pool and subsequent decrease in K63-linked polyubiquitination of monocarboxylate transporter 1 (MCT1). This ubiquitination defect led to destabilization of MCT1 and was associated with a global increase in protein lactylation in EMMPRIN-deficient models. Furthermore, EMMPRIN suppression inhibited several signaling pathways critically involved in MASH pathogenesis, including PPAR signaling, Notch signaling, and TGF-β-mediated fibrotic response.

Conclusion: Our findings demonstrate that EMMPRIN promotes MASH progression through the UBA52-MCT1 regulatory axis, which modulated ubiquitin-dependent protein stability and induced metabolic reprogramming, thereby driving lipid accumulation, inflammation, and fibrosis. These results position EMMPRIN as a promising therapeutic target for MASH intervention.

The increasing use of extended kidney grafts to bridge organ shortage has led to delayed and impaired graft function, warranting the development of new preservation strategies. In addition to hypothermic machine perfusion, the addition of pharmacological agents to preservation solutions has been primarily investigated, with a few promising agents making their way into clinical trials. This review aimed to identify and summarize current literature studies on pharmacological treatment additives for hypothermic kidney graft preservation. A scoping review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. A comprehensive literature search was performed using Medline and Cochrane Library databases until 1 December 2023. All studies published in English reporting on pharmacological supplementation of preservation solutions to improve hypothermic kidney graft preservation were included. A total of 67 records were retrieved, all of which were preclinical except one. Of these, 8 were conducted on cellular models, 21 on ex vivo kidneys, and 38 on animal kidney transplantations. A total of 40 pharmacological agents were evaluated based on the key markers of ischemia-reperfusion injury (IRI) pathophysiology, most of them showing promise in kidney preservation. Although promising, with numerous preclinical studies identifying various effective additives, the pharmacological treatment additive strategy to improve hypothermic kidney preservation has still not been translated into clinical practice. Clinical investigations should be promoted to support few ongoing trials offering encouraging outcomes.

Background: The relationship between oral iron preparation-related gastrointestinal adverse events (AEs) and medication adherence in female patients with iron deficiency anemia (IDA) remains unclear.

Objective: To assess gastrointestinal AEs linked to oral iron preparations via the US FDA Adverse Event Reporting System (FAERS), evaluate medication adherence levels in female IDA patients, and analyze the impact of gastrointestinal AEs and other factors on their medication adherence.

Methods: Reporting odds ratio (ROR) and Proportional Reporting Ratio (PRR) were used to analyze oral iron preparation-related gastrointestinal AEs. The Medication Adherence Report Scale-5 (MARS-5) was used to assess patients' medication adherence, while logistic regression analyzed the impact of factors (gastrointestinal AEs, medication beliefs, illness perception, doctor-patient relationship, social support) on medication adherence.

Results: FAERS recorded 2,624 reports of gastrointestinal AEs following oral iron supplementation in female patients with IDA (January 2000-March 2025). Disproportionality analysis indicated that ferrous fumarate exhibited the weakest gastrointestinal AE disproportional reporting signal (ROR = 0.36, 95% CI 0.27-0.48; PRR = 0.44), with no positive signals detected, whereas ferrous gluconate displayed the strongest signal (ROR = 2.62, 95% CI 2.05-3.34; PRR = 1.90) and the most prominent positive signals. No significant gastrointestinal AE disproportional reporting signals were found for ferrous sulfate or iron polysaccharide complex. A cross-sectional study (148 patients) showed that adherent patients and non-adherent patients accounted for 64.86% and 35.14%, respectively. Multivariate logistic regression analysis indicated that gastrointestinal AEs were not significantly associated with medication adherence, while medication concern beliefs, doctor-patient relationship, and hemoglobin level were important factors affecting medication adherence in female IDA patients.

Conclusion: Gastrointestinal AEs are not a key factor affecting medication adherence. Reducing patients' medication concerns, improving the doctor-patient relationship and reinforcing counseling to avoid premature medication withdrawal due to elevated hemoglobin levels are beneficial to enhancing medication adherence in female IDA patients.

Neglected tropical diseases (NTDs) are a distinct group of illness that are primarily prevailing in the tropical regions. NTDs are caused by diverse pathogens including viruses, bacteria, parasites, fungi and toxins, resulting in adverse health, social and economic outcomes. Currently, more than one billion people globally are affected with NTDs, therefore, precise and rapid diagnostic mechanisms are integral for detection and control of NTDs. However, the NTDs programs are underinvested in the progression and enhancement of diagnostic tools. Due to this reason, WHO has released a new road map for NTD 2021-2030 and has pinpointed diagnostics as one of the precedence areas that require concrete action. In order to achieve the 2030 targets, WHO has also established Diagnostic Technical Advisory Group (DTAG) which will help in initiating collaboration among nations to drive advancement in this area. In this review, we explored the epidemiology and burden of NTDs, the challenges in their mitigation, and the available therapeutic interventions for managing these diseases. We have also highlighted the need to holistic approach like "One health" for an effective elimination of NTDs in affected areas. Elimination of NTDs will enhance the socioeconomic levels of the affected regions, thereby assisting in the accomplishment of few sustainable development goals. Thus, there is a need for worldwide commitment for funding to develop fast and safe therapeutic and diagnostic strategies for NTDs.

Background: With the development of cardiac rehabilitation (CR), the advantages of combined Chinese and Western medicine cardiac rehabilitation for the treatment of stable coronary artery disease (SCAD) have become increasingly prominent.

Purpose: This study was aimed to evaluate the effect of Zhenyuan capsule (a Chinese patented medicine consisting of ginseng berry saponins extracted from the mature berry of Panax Ginseng) on cardiorespiratory fitness (CRF) in patients with SCAD, and explore possible potential candidate molecule.

Study design and methods: Using a randomized, double-blind, placebo-controlled trial design, 100 patients with SCAD were enrolled and randomly divided into the group taking Zhenyuan capsules (test group, n = 50) and the group taking placebo (control group, n = 50). In both groups, patients were treated with secondary prevention medication for CHD, with the addition of 2 capsules of Zhenyuan capsule 3 times a day for 12 weeks in the test group and 2 capsules of placebo 3 times a day for 12 weeks in the control group, with a follow-up of 1 month after the end of treatment. Subjects completed symptom-limited maximal cardiopulmonary exercise test (CPET) on a bicycle ergometer at 3 time points before enrollment, after 12 weeks of treatment, and after 1 month of follow-up. The main outcome was the increase in metabolic equivalent.

Results: Both at anaerobic threshold (AT) level and at maximal level, the results of between-group comparisons showed that the test group was significantly better than that of the control group after treatment (AT level: 0.58 ± 0.89 Mets vs. 0.15 ± 1.06 Mets; maximal level: 0.69 ± 0.92 Mets vs. 0.19 ± 0.93 Mets) (P < 0.05). No serious adverse events occurred in patients in both groups. Serum proteomics studies suggested that insulin-like growth factor II (IGF2) was downregulated in a minority of responders, potentially related to cholesterol metabolism and the PI3K-Akt pathway.

Conclusion: Zhenyuan capsule can significantly improve the CRF of patients with SCAD, and the downregulation of IGF2 observed in a minority of responders suggests IGF2 may be a potential candidate molecule of interest associated with cholesterol metabolism and the PI3K-Akt pathway.

Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=53361, identifier ChiCTR2000032818.