Papillary thyroid microcarcinoma (PTMC) is a prevalent endocrine malignancy, and metastatic progression remains a major clinical concern. Identifying novel therapeutic strategies and metastasis-associated targets is therefore urgently needed. Integrated transcriptomic analyses were performed using TCGA and GEO datasets to identify metastasis-associated genes and biological pathways in PTMC. Functional enrichment, immune infiltration analysis, single-cell RNA sequencing analysis, and external validation were conducted to characterize candidate genes. The connectivity map (CMap) database was used for drug screening, followed by network pharmacology, molecular docking, and molecular dynamics simulations to evaluate potential therapeutic candidates. In vitro assays, including proliferation, migration, invasion, macrophage co-culture experiments, and Western blot analysis, were performed to evaluate the biological effects of the candidate drug. Twenty differentially expressed genes were identified between metastatic and non-metastatic PTMC samples, among which AREG and HBEGF were prioritized as hub candidates. HBEGF showed a negative correlation with tumor mutational burden, although its biological significance requires further investigation. Enrichment analyses suggested that ErbB signaling may be involved in PTMC metastatic progression. External validation using an independent GEO cohort provided additional support for the association between HBEGF expression and metastatic characteristics. CMap-based screening identified talniflumate as a potential therapeutic candidate. In vitro experiments demonstrated that talniflumate suppressed proliferation, migration, and invasion of thyroid cancer cells. Furthermore, talniflumate promoted M1 macrophage polarization and increased pro-inflammatory cytokine secretion in a cancer cell–macrophage co-culture model. Western blot analysis showed reduced HBEGF protein expression following talniflumate treatment, suggesting a potential regulatory effect on the HBEGF-associated signaling network. This study identifies HBEGF as a potential metastasis-associated candidate in PTMC and suggests that talniflumate may represent a promising therapeutic candidate. The proposed HBEGF-associated regulatory mechanism provides a potential direction for further investigation, while larger independent cohorts and additional mechanistic studies are required for validation.
The European Medicines Agency (EMA) is an institution of the European Union (EU), responsible for the authorization and pharmacovigilance of medicinal products. In our study, we present a systematic analysis of the 1,985 centralized EMA marketing authorization procedures (MAP) between 1995 and 2025. The analysis mainly includes EMA marketing authorizations, withdrawals of marketing authorizations, and revocations of marketing authorizations or refusals of drug applications. With regard to the analysis period, it is evident that the number of marketing authorizations recommended by the EMA increased significantly between 1996 (first fully published evaluation year) and 2025. Among the active substances (International Nonproprietary Names, INNs) in centralized EMA MAPs, clopidogrel and denosumab are the most frequently represented. On the other hand, antineoplastic agents and immunosuppressants are the most common therapeutic subgroups according to the Anatomical Therapeutic Chemical Classification (ATC) in MAPs. Notably, special MAPs for medicines such as generics, biosimilars, and medicines for the treatment of rare diseases (orphan medicines) account for more than 30
Type 1 reaction (T1R) is an inflammatory complication of leprosy that can affect skin and peripheral nerves, but the lesion-level host-response genes distinguishing reactional from non-reactional borderline disease remain incompletely defined. This study analysed the GSE74481 skin-lesion transcriptomic dataset to compare T1R_R1 lesions with borderline non-reaction lesions and used an evidence-guided prioritisation approach to organise the lesion-derived expression signal. Differential expression analysis of 44 skin-lesion samples identified 3630 differentially expressed genes, including 1979 upregulated and 1651 downregulated genes in T1R_R1 lesions. T1R_R1-upregulated genes were enriched for immune-cell recruitment, interleukin-related signalling, neutrophil activation and extracellular matrix organisation, whereas borderline non-reaction lesions showed stronger epithelial and skin-development programmes. Co-expression and candidate-prioritisation analyses identified 23 final Tier 1 candidates within this broader inflammatory and tissue-remodelling response, including genes linked to myeloid activity, oxidative response, cytokine-interferon-related signalling, endothelial interaction and matrix remodelling. The final candidate signature showed within-cohort separation of T1R_R1 from borderline non-reaction lesions, with an apparent internal AUC of 0.955. Most detected skin-derived candidates also showed the same direction of change in the blood-based GSE269151 T1R contrast, supporting partial cross-tissue direction-of-effect concordance. DGIdb and ChEMBL analyses linked representative candidates, including JAK2, ICAM1 and TNF, to existing drug-gene or target-level annotations, providing pharmacological context for hypothesis generation. These findings define a discovery-stage lesion-derived T1R host-response profile and prioritise candidate genes for future validation in independent lesion cohorts and experimental systems.
Cisplatin (CP) is a highly effective, heavy-metal chemotherapeutic agent widely utilized in the treatment of various solid tumors. But its use in therapeutic settings is fundamentally constrained by dosage toxicities, most notably severe nephrotoxicity. Aloesin, a bioactive C-glycosylated chromone naturally derived from Aloe vera, possesses strong antioxidant and anti-inflammatory properties. This investigation clarifies the precise molecular mechanisms by which aloesin attenuates CP-induced renal injury in a rodent model. A total of 36 male Wistar rats were randomly assigned to six experimental groups: (I) Normal control (vehicle only), (II) CP (5 mg/kg, i.p.), (III) CP + Aloesin (20 mg/kg, p.o.), (IV) CP + Aloesin (40 mg/kg, p.o.), (V–VI) Aloesin alone (20 and 40 mg/kg, p.o.). The study followed a preventive design; aloesin was administered orally throughout the 25-day experimental period, concurrent with CP. Nephrotoxicity was induced in the respective groups via four intraperitoneal injections of CP (5 mg/kg) administered at 5-day intervals (days 1, 6, 11, and 16). At the conclusion of the 25-day timeline, physiological parameters, serum creatinine (Scr), blood urea nitrogen (BUN), and lipid profiles were evaluated. Additionally, inflammatory modulators (TNF-α, IL-1β, IL-6, NF-κB), tissue apoptotic indicators (Caspase-3, Caspase-9, Bax, Bcl-2), and oxidative stress markers (MDA, SOD, GSH, CAT) were quantified from renal tissue homogenates alongside semi-quantitative histopathological evaluation. CP administration induced profound renal impairment, characterized by elevated Scr and BUN, extensive lipid peroxidation, and the depletion of endogenous antioxidants. Concurrent treatment with aloesin significantly preserved renal function, reduced MDA levels, and restored SOD, CAT, and reduced GSH activities. Furthermore, aloesin significantly reduced renal tissue levels of NF-κB, TNF-α, IL-1β, IL-6, Bax, Caspase-3, and Caspase-9, while improving Bcl-2 levels and decreasing the Bax/Bcl-2 ratio, suggesting attenuation of inflammatory and apoptotic pathways. Histopathological evaluation confirmed that aloesin effectively preserved renal tubular morphology without causing any independent physiological or systemic toxicity. These findings demonstrate that aloesin exerts robust prophylactic nephroprotective efficacy against CP-induced acute kidney injury. This protective action is driven by the clear suppression of oxidative stress, restriction of macro-inflammatory signaling, and the direct inhibition of mitochondrial-mediated apoptotic pathways.
The skin-brain axis is a bidirectional neuroimmune network linking cutaneous inflammation with central neuroinflammation, stress signaling, and behavioral disturbances. This review summarizes the mechanisms underlying skin-brain communication and evaluates current and emerging pharmacological strategies targeting this axis in inflammatory skin disorders. We synthesized contemporary experimental, translational, and clinical evidence on neuroimmune signaling across the skin-brain axis, with emphasis on sensory neuron-immune cell interactions, neurogenic inflammation, glial activation, pharmacological targets, biomarkers, disease models, and artificial intelligence (AI)-enabled precision approaches. Current evidence suggests that chronic cutaneous inflammation may promote central neuroimmune activation through neuropeptides, cytokines, and stress-responsive pathways. Central stress signaling can, in turn, exacerbate skin disease. Substance P, calcitonin gene-related peptide, transient receptor potential channels, microglia, and astrocytes emerge as key mediators linking peripheral inflammation to altered neuroplasticity and affective symptoms. Therapeutic approaches including biologics, Janus kinase and phosphodiesterase-4 inhibitors, neuromodulators, and transient receptor potential antagonists show promise in reducing pruritus and neuropsychiatric comorbidity. However, pharmacodynamic variability and incomplete response remain important limitations. Biomarkers, multi-omic profiling, and advanced preclinical models may improve translational evaluation, while AI tools may support biomarker discovery, digital phenotyping, and individualized treatment selection. The skin-brain axis represents a pharmacologically actionable framework for inflammatory skin disease. Integrated strategies addressing peripheral inflammation, central neuroimmune dysregulation, and psychosocial burden may improve precision pharmacotherapy and clinical outcomes.
Baloxavir marboxil is a novel antiviral agent; however, the accuracy of medication-related information available on social media remains uncertain. This study aimed to systematically evaluate the content coverage, quality, and reliability of short videos related to baloxavir marboxil on Douyin and Xiaohongshu. The top 100 baloxavir marboxil–related videos were collected from both Douyin and Xiaohongshu. Quality and reliability were assessed using the JAMA criteria, modified DISCERN (mDISCERN), Global Quality Score (GQS), and the medication information items (MII) checklist. Correlations between video quality and user engagement metrics were also analyzed. A total of 176 eligible videos were included. While videos on Xiaohongshu demonstrated higher quality and reliability than those on Douyin, Douyin videos showed greater engagement. Median JAMA scores were 2.00 (Xiaohongshu) and 1.00 (Douyin); mDISCERN scores were 2.00 on both; GQS scores were 3.00 on both; and MII values were 3.00 and 2.00, respectively. A substantial proportion of videos scored poorly on JAMA-2, JAMA-4, mDISCERN-2, and mDISCERN-4. Physicians and individual users were the main uploaders. Most videos employed a monologue format and focused on indications. Videos uploaded by pharmacists had higher quality and greater medication information coverage, and were the most engaging. Although video quality was not correlated with popularity, MII was a significant predictor of high-quality videos. Misinformation mainly involved exaggerated efficacy, pharmacological misunderstandings, inappropriate self-medication, incorrect indications, misleading safety claims, and commercial exaggeration. The quality and reliability of baloxavir marboxil–related videos on Douyin and Xiaohongshu remain suboptimal, with notable deficiencies in source referencing. Significant differences in video quality exist between platforms, highlighting the need for users to exercise discernment when accessing related content. This study underscores potential disparities in access to high-quality health information across user groups on short video platforms, as well as the associated health equity issues. Future efforts should focus on characterizing misinformation related to baloxavir marboxil on short video platforms. Additionally, social media platforms should establish policies to review and monitor health education content to ensure the public receives accurate and trustworthy health information.
Splenomegaly is a clinically important complication in transfusion dependent beta thalassemia major because spleen enlargement may worsen anemia, transfusion burden and patient discomfort. This study assessed splenomegaly severity, related clinical burden, serum ferritin patterns and longitudinal clinical outcomes during routine transfusion and chelation care. This cohort study was conducted at Thalassemia Care Centre Nawabshah from March to August 2025. Patients with transfusion dependent beta thalassemia major were enrolled during routine transfusion visits. Baseline and follow up assessments included clinical history, chelation status, hemoglobin, serum ferritin, ultrasound-based spleen length and width and splenomegaly related symptoms. Patients were grouped by splenomegaly severity. Baseline groups were compared and ferritin spleen relationships were examined. Longitudinal changes in hemoglobin, spleen measurements and ferritin were evaluated using repeated measures models. The final cohort comprised 515 patients. Mean age was 7.39 ± 5.47 years, and mean serum ferritin was 2491.91 ± 806.46 ng/mL. Normal spleen was observed in 70 patients (13.6
White peony root (Paeonia lactiflora Pall.) is the dried root of peony. White peony root has a long history in Traditional Chinese Medicine (TCM) and is primarily used to treat various conditions, including pain, inflammation, and immune system disorders. Paeoniflorin (PF) is one of the main active components of white peony root, and it has multiple functions such as anti-inflammation, immune regulation, and neuroprotection. However, the impact of PF on multiple sclerosis (MS) remains to be fully elucidated. In this study, we observed that PF treatment markedly attenuated neurological symptoms in experimental autoimmune encephalomyelitis (EAE) mice, reduced disease severity, and alleviated spinal cord inflammation and demyelination, indicating a significant neuroprotective effect. PF administration was accompanied by reduced CD4+ T cell infiltration, decreased Th17 cell proportions, and increased Treg cell frequency in vivo. It also balanced Th17/Treg-associated cytokine secretion by suppressing IL-17 and promoting IL-10 expression. In addition, PF modulated the expression of differentiation-related proteins in lymphoid tissues and inhibited inflammatory gene and protein levels. In primary murine CD4+ T cells, PF enhanced Treg differentiation under Treg-polarizing conditions. In Jurkat cells, PF induced phosphorylation of Raf, MEK1/2, and ERK1/2, together with increased expression of Egr-1 and Foxp3. These findings indicate that PF treatment is associated with modulation of the Treg/Th17 balance in EAE mice and with changes in Raf/MEK1/2/ERK1/2/Egr-1 signaling in Jurkat cells. In summary, PF treatment ameliorated EAE manifestations, together with restoration of Treg/Th17 homeostasis and activation of the Raf/MEK1/2/ERK1/2/Egr-1 pathway. However, whether the Raf/MEK1/2/ERK1/2/Egr-1 signaling axis directly contributes to PF-induced Treg differentiation in primary T cells or to the therapeutic effects of PF in vivo remains to be determined. PF treatment ameliorated EAE manifestations and was associated with reduced CD4+ T-cell infiltration, restoration of the Th17/Treg balance, and attenuation of CNS inflammation and demyelination in EAE mice. PF also enhanced Treg differentiation in primary murine CD4+ T cells and was associated with the activation of the Raf/MEK1/2/ERK1/2/Egr-1 signaling axis in Jurkat cells. The causal contribution of this signaling axis to Treg differentiation and the therapeutic effects of PF remains to be determined.
Antimicrobials are among the most frequently used drug classes in neonates, yet their safety profile remains incompletely characterized because neonatal pharmacokinetics, organ immaturity, off-label prescribing, and under-reporting complicate adverse event (AE) detection. This review aimed to synthesize published evidence on antimicrobial-associated AEs in neonates and to contextualize these findings using pharmacovigilance signals from the FDA Adverse Event Reporting System (FAERS). A structured literature review was conducted in PubMed, Embase, and the Cochrane Library to identify studies reporting AEs associated with antimicrobial exposure in neonates and preterm infants. In parallel, FAERS reports from Q1 2004 to Q2 2024 were retrieved through OpenVigil 2.1 for 12 commonly used antimicrobial agents: gentamicin, vancomycin, fluconazole, ampicillin, amphotericin B, metronidazole, piperacillin, meropenem, amikacin, amoxicillin, voriconazole, and cefotaxime. Reporting odds ratio, proportional reporting ratio, and Bayesian confidence propagation neural network analyses were used to identify disproportionality signals. AEs were classified using MedDRA Preferred Terms(PTs) and System Organ Classes (SOCs). Published evidence grouped neonatal antimicrobial-associated AEs into three clinically relevant categories: secondary or resistant infections, immediate organ toxicity, and longer-term developmental or metabolic sequelae. The FAERS analysis identified 639 eligible neonatal reports and 97 disproportionality signals across 20 SOCs. The most frequently represented categories were infections and infestations, gastrointestinal disorders, and hepatobiliary disorders. Prominent PTs included systemic Candida infection, necrotizing enterocolitis neonatal, sepsis, respiratory disorder, multiple organ dysfunction syndrome, liver abscess, intestinal obstruction, hepatotoxicity, and tubulointerstitial nephritis. Notably, intestinal obstruction was associated with fluconazole (ROR: 75.95) and ampicillin (ROR: 59.51); capillary leak syndrome was detected for amphotericin B (ROR: 312.26) and fluconazole (ROR: 296.66); and multiple organ dysfunction syndrome was observed with voriconazole (ROR: 65.13) and fluconazole (ROR: 52.86). These signals are insufficiently characterized in the neonatal antimicrobial safety literature and warrant further investigation. This review provides a comprehensive synthesis of literature and pharmacovigilance data to support cautious and individualized antimicrobial use in neonates. Given the multifactorial nature of neonatal outcomes, these findings should be interpreted as associations rather than definitive causal relationships. Clinically, our results support conservative antimicrobial stewardship, individualized dosing, and organ-specific monitoring in routine neonatal intensive care unit (NICU) care. Future research should prioritize gestational age-stratified analyses and prospective registries linking antimicrobial exposure to long-term outcomes to define drug-specific safety profiles.
Antibiotic therapy is losing effectiveness against resistant pathogens like Staphylococcus aureus (SA) strains with reduced susceptibility to vancomycin (VMN), particularly in bone infections where drug delivery is difficult. Hyperthermia has emerged as a potential alternative, yet its specific impact on infected bone remains poorly understood. This study investigated the systemic and local effects of combining VMN with local thermal exposure on inflammation and regeneration in rat femurs locally infected with SA strain 209 P insensitive to VMN at an in vitro dose of 10 µg/mL. In vitro, SA growth was assessed after heating at 45 °C and 60 °C for up to 60 min. In vivo experiments involved six groups of rats that received local hyperthermia (45 °C) or thermal ablation (60 °C) for 20 min, with or without systemic VMN administration. At 45 °C, a bacteriostatic effect was achieved after 45–60 min, whereas 60 °C inhibited growth completely within 15 min. In post-hyperthermia at 45 °C, bone tissue showed a regenerative effect comparable to VMN alone and significantly reduced local inflammation. Unexpectedly, combined treatment partially weakened this regenerative benefit. Thermal ablation at 60 °C, while inducing bone regeneration, also elevated markers of systemic inflammation like blood leukocytosis and weight loss, which were partially mitigated by VMN. However, antibiotic showed a negligible effect on local inflammation and reparative processes at this higher temperature. The findings indicate that a single hyperthermia session has more biological promise than thermal ablation as a targeted approach to limit local and systemic inflammation in SA-complicated trauma. Nevertheless, the complex interactions between high temperature and antibiotics warrant further investigation to determine optimal combined therapeutic regimens for osteomyelitis.
Steroid-resistant nephrotic syndrome (SRNS) is a major cause of kidney failure and remains a clinical challenge. Bibliometric analysis offers a quantitative approach to reveal research patterns and hotspots, yet, to our knowledge, no bibliometric analysis has focused specifically on SRNS. To summarize global research trends and future directions in SRNS. Publications related to SRNS from 1 January 1999 to 14 June 2026 were retrieved from the Web of Science Core Collection (WoSCC) database. Bibliometric analyses were performed using VOSviewer, CiteSpace, and RStudio. A total of 1,720 eligible articles and reviews from 91 countries were included. Annual publication output increased overall, although the 2026 data represented an incomplete year. The United States ranked first in both publications and citations; the University of Michigan, Friedhelm Hildebrandt, and Pediatric Nephrology were the most productive institution, author, and journal, respectively. Keyword analysis showed a transition from podocyte proteins and gene mutations toward multicenter cohorts, genetic testing, kidney transplantation, variants, and chronic kidney disease. The three most frequently co-cited references were Sadowski et al. (2015), Boute et al. (2000), and Ruf et al. (2004). This study maps the global SRNS literature and identifies major research trends and emerging themes, providing a reference for investigations into the pathogenesis, diagnosis, and treatment of SRNS.
Risankizumab is a humanized monoclonal antibody that selectively targets the interleukin-23 p19 subunit. It has demonstrated lasting therapeutic effects in a variety of diseases. Previous bibliometric studies have carried out macro-level mapping in the field of biologic agents for psoriasis. However, no systematic knowledge-map analysis has been conducted specifically for risankizumab. To fill this research gap, this study combines bibliometric and narrative pharmacological approaches. Relevant literature published between January 2016 and December 2025 was retrieved from the Web of Science Core Collection and the Scopus database. Two researchers independently screened the literature and included a total of 2,053 eligible publications, then performed the analyses using Bibliometrix, VOSviewer, CiteSpace, and Microsoft Excel. The results show that the number of drug-related research publications has increased substantially, from only 9 articles in 2016 to nearly 500 in 2025. The United States ranks first in publication volume (n = 1,130), followed by AbbVie as the most productive institution (n = 147) and Matteo Megna as the most prolific author (n = 55). Relevant findings are mainly published in journals such as the International Journal of Molecular Sciences, Annals of the Rheumatic Diseases, JAMA, and The Lancet. Keyword co-occurrence analysis identified 20 independent clusters (Q = 0.9069, S = 0.9776). By integrating bibliometric data with pharmacological background, this study presents the first comprehensive knowledge atlas of the risankizumab research field, offering practical references for future investigations on this drug.
Cardiovascular aging is the progressive deterioration of heart and blood vessel function with advancing age. Despite advances in cardiovascular research, no specific therapy is currently available to prevent cardiac aging. Andrographolide, a bioactive diterpenoid, has shown cardioprotective potential, but its role in cardiac aging remains inadequately explored. To evaluate the mechanistic role of andrographolide in attenuating cardiac aging, with a particular focus on mitochondrial homeostasis. Cardiac aging was induced in male C57BL/6J mice by intraperitoneal administration of D-galactose (50 mg/kg/day). Mice were divided into control, andrographolide (50 mg/kg), D-galactose, and D-galactose + andrographolide (50 mg/kg). Andrographolide was administered orally for 8 weeks. Cardiac tissues were analyzed for oxidative stress, inflammation, apoptosis, and mitochondrial biogenesis–related markers TFAM, PGC-1α, and SIRT-1. Andrographolide treatment significantly improved cardiac function in D-galactose–induced aged mice. It enhanced antioxidant defenses while reducing inflammation and apoptosis. Immunohistochemical analysis demonstrated increased expression of SIRT1, PGC-1α, TFAM, and Nrf2, suggesting that andrographolide may promote mitochondrial biogenesis and antioxidant defense. Andrographolide confers significant cardioprotection against induced cardiac aging by modulating oxidative, inflammatory, and mitochondrial regulatory pathways. Thus, andrographolide can act as an ameliorative therapeutic drug for management of cardiac aging, warranting further mechanistic and translational investigations.
Road traffic noise (RTN), an emerging environmental stressor, has been linked to adverse gestational outcomes; however, its impact on offspring early reproductive development and potential pharmacological interventions remain insufficiently explored. Oxidative stress and inflammation are considered key mechanisms underlying prenatal stress-induced developmental programming. The current study aims to investigate whether maternal administration of melatonin (MLT) and edaravone (EDV), individually or in combination, can protect against prenatal RTN-induced early testicular development in male offspring and to assess environmental enrichment (EE) as an independent non-pharmacological approach to preserve normal reproductive development. Pregnant Sprague–Dawley rats were randomly assigned to six groups: control, RTN (100 dB(A) SPL), RTN + MLT (5 mg/kg/day, i.p.), RTN + EDV (5 mg/kg/day, i.p.), RTN + MLT + EDV, and EE (independent). Male offspring were evaluated on postnatal day 21 for reproductive organ weights; testicular oxidative stress markers (TBARS and NO₂⁻); antioxidant enzymes (GSH, SOD, and CAT); inflammatory cytokines (TNF-α and IL-6); serum testosterone levels; and testicular histopathological changes. Prenatal RTN exposure was found to be a significant cause of reduced reproductive organ weights, testosterone concentrations, and antioxidant enzyme activities, while increasing lipid peroxidation, nitro-oxidative stress, and pro-inflammatory cytokine levels. The combined gestational administration of MLT and EDV conferred superior restoration of prenatal RTN-induced adverse redox homeostasis, inflammatory status, and testicular structure of offspring compared with either agent alone. However, providing environmental enrichment alone during the gestational period avoided adverse reproductive programming in offspring. The findings identify RTN as a modifiable prenatal environmental risk factor and suggest MLT and EDV as promising pharmacological strategies for mitigating RTN-associated early testicular developmental alterations. Independently, optimized gestational EE was associated with favorable early testicular development. These findings warrant further mechanistic and translational investigation. Prenatal road traffic noise impairs early testicular development in Sprague-Dawley offspring
Colorectal cancer is one of the most common malignancies worldwide and remains a major cause of cancer-related mortality. Therefore, the identification of novel compounds with selective anticancer activity represents an important research priority. Dihydroisoxazole derivatives represent a promising class of heterocyclic compounds with potential antitumour properties. This study evaluated the anticancer effects of the dihydroisoxazole derivative DHI9 in human colorectal cancer cell lines HCT116 and Caco-2 and investigated the molecular mechanisms involved. The cytotoxic effect of DHI9 was determined using the MTT assay, revealing IC50 values of 2.5 µM in HCT116 cells and 10.0 µM in Caco-2 cells after 72 h treatment. In non-tumour CCD-18Co cells, the IC50 value was 127.3 µM, indicating promising selective cytotoxicity toward the tested colorectal cancer cells. All subsequent biological and mechanistic experiments were performed exclusively in HCT116 and Caco-2 cancer cells. In these cancer cells, DHI9 inhibited cell proliferation, induced G2/M cell cycle arrest after 24 h, and caused a time-dependent increase in the sub-G0/G1 cell population. Furthermore, DHI9 also increased p21 expression, ROS production, and phospho γH2A.X levels, indicating oxidative stress and activation of the DNA damage response. Apoptosis induction was confirmed by phosphatidylserine externalization, loss of mitochondrial membrane potential, cytochrome c release, and increased caspase-9 and caspase-3/7 activity. In addition, fluorescence microscopy showed changes in nuclear morphology and actin cytoskeleton organization. Western blot analysis demonstrated that DHI9 modulated selected proteins involved in Wnt/β-catenin and Akt signalling pathways, apoptosis, and cell cycle regulation, including PCNA, Dvl2, p-Akt, p-GSK-3β, total GSK-3β, β-catenin, non-phosphorylated β-catenin, PARP, p-Rb, p-Wee1, p-Cyclin B1, and p-Cdc2. Moreover, DHI9 also reduced the migration of both colorectal cancer cell lines and enhanced the cytotoxic activity of 5-fluorouracil, with predominantly synergistic interactions according to the Highest Single Agent model.
Ovarian cancer is characterized by extensive molecular heterogeneity and poor clinical outcomes, highlighting the need to identify biologically relevant therapeutic targets. NCCRP1 remains poorly characterized in ovarian cancer, and its molecular and therapeutic significance is largely unknown. In this study, we applied an integrative multiomics framework incorporating transcriptomic profiling, survival analysis, immune microenvironment characterization, pathway and network analyses, pharmacogenomic assessment, structural modeling, and single-cell RNA sequencing to investigate the role of NCCRP1 in ovarian cancer. Family-wide screening of the TCGA-OV cohort identified NCCRP1 as the only member significantly associated with overall survival. Elevated NCCRP1 expression was enriched in tumor tissues and associated with adverse clinical outcomes. Functional analyses demonstrated that NCCRP1-high tumors exhibit activation of epithelial-mesenchymal transition, cytoskeletal remodeling, adhesion signaling, and hypoxia-associated pathways, suggesting involvement in tumor plasticity and progression. Network-based analyses further positioned NCCRP1 within regulatory programs linked to structural reorganization and aggressive tumor phenotypes. Single-cell RNA sequencing confirmed that NCCRP1 expression is predominantly localized to malignant epithelial populations, supporting a tumor-intrinsic role. Pharmacogenomic analyses identified NCCRP1-associated transcriptional states linked to distinct drug sensitivity patterns, while structural modeling suggested the presence of a surface-accessible cavity capable of accommodating small molecules. Although these findings require experimental validation, they provide preliminary evidence supporting the potential druggability of NCCRP1. Our findings provide a comprehensive molecular characterization of NCCRP1 and support its prioritization as a candidate therapeutic target in ovarian cancer. This study demonstrates the utility of integrating multiomics, pharmacogenomic, structural, and single-cell approaches for therapeutic target discovery and prioritization in cancer.
SMMC-7721 has long been used as a presumed human hepatocellular carcinoma model, but authentication studies have shown that it is HeLa-derived rather than a genuine liver cancer cell line. This short communication discusses the consequences of using SMMC-7721 as an HCC model in a recent study on quercetin-induced immunogenic cell death and cGAS-STING pathway activation in hepatocellular carcinoma cells. Because data generated in SMMC-7721 reflect a HeLa-derived cellular background, conclusions regarding anti-HCC activity, liver-cancer-specific mechanisms, compound selectivity, and therapeutic relevance require qualification or reassessment in authenticated hepatocellular carcinoma models. The commentary emphasizes the importance of cell-line authentication, appropriate model selection, and transparent reporting to ensure reliability and reproducibility in preclinical liver cancer research.
Propofol is a widely used intravenous anesthetic, yet its potential epileptogenic effects remain underexplored in large-scale studies. This pharmacovigilance study leveraged data from the FDA Adverse Event Reporting System (FAERS) to investigate seizures associated with propofol. Disproportionality analysis, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS), was applied to FAERS data (Q1 2004–Q1 2025). Reports of propofol-related seizures were analyzed for signal strength, clinical prioritization, time to onset, and outcome severity. Stratified analyses examined the effects of demographic factors and concomitant antiepileptic drugs (AEDs). Among 19,026,509 reports, propofol was identified as the primary suspected drug in 7945 cases, with 322 seizure-related events reported. Propofol was significantly associated with disproportionate reporting of seizure-related adverse events across 14 preferred terms (PTs), with 11 signals validated by all four disproportionality methods. Time-to-onset analysis revealed a median of 0 days with an early-failure pattern. Clinical prioritization classified 13 of 14 signals as being of moderate concern. Serious outcomes occurred in 63.98
The present study aimed to evaluate the pharmacokinetic and pharmacodynamic performance of an optimized prasugrel hydrochloride-loaded nanosponge formulation (PSG-NS) following oral administration and to compare its systemic exposure and antiplatelet efficacy with a marketed prasugrel tablet formulation. PSG-NS was orally administered to male Wistar rats at a dose equivalent to 5 mg/kg and compared with a marketed prasugrel tablet suspension (Prasita®). Plasma concentrations were quantified using an RP-HPLC–UV method and analyzed using non-compartmental and compartmental pharmacokinetic approaches. Pharmacodynamic efficacy was evaluated using ADP-induced platelet aggregation and a ferric chloride-induced carotid artery thrombosis model. The PSG-NS formulation demonstrated significantly enhanced systemic exposure compared with Prasita®. PSG-NS achieved a significantly higher Cmax (1245.6 ± 68.3 ng/mL) with a shorter median Tmax of 0.5 h (0.5–1.0 h) compared with Prasita®, which exhibited a Cmax of 456.2 ± 31.4 ng/mL and a median Tmax of 1.0 h (0.5–2.0 h) (p < 0.001). The AUC0–∞ increased from 3412.7 ± 198.5 to 8456.3 ± 456.2 ng h/mL, corresponding to a 2.48-fold increase, indicating substantially greater systemic exposure following PSG-NS administration than Prasita®. PSG-NS also produced significantly greater inhibition of ADP-induced platelet aggregation (78.0 ± 4.2
The interrelationship of mechanistic target of rapamycin (mTOR), brain-derived neurotrophic factor (BDNF), NMDA receptor and neuronal survival during early cerebral ischemia–reperfusion is not certain. We investigated this relationship by using MK-801, a non-competitive NMDA receptor antagonist and by determining infarct size and blood–brain barrier (BBB) disruption under the condition of markedly reduced mTORC1 activity. Rats received rapamycin (20 mg/kg, i.p.) for two days before transient middle cerebral artery occlusion (MCAO). At 15 min after MCAO, half of the rats received MK-801 (5 mg/kg i.v.). At two hours’ reperfusion after 90 min MCAO, BBB permeability, plasma volume and infarct size were determined. In rats without MCAO, one hour after MK-801, protein levels of pS6 (Ser240/244), pAkt (Ser473), mBDNF, proBDNF and MMP-2 were analyzed by Western blot. MK-801 reduced the percentage of cortical infarct in the Control (8.4
