Drug Research最新文献

Glioblastoma multiforme continues to pose a major therapeutic challenge due to its high level of treatment resistance and poor prognosis. Temozolomide is a standard chemotherapeutic agent, but resistance significantly limits its clinical efficacy. This study investigated the potential of resveratrol to overcome temozolomide resistance in glioblastoma cells by examining its effects on molecular mechanisms of drug resistance. Human glioblastoma cell lines U251 and temozolomide-resistant U251/temozolomide were utilized. Cellular viability was assessed using the MTT assay. Molecular mechanisms were evaluated through qRT-PCR, Western blotting, Rhodamine 123 accumulation, and apoptosis detection techniques. The study examined alterations in P-glycoprotein (P-gp) expression, mitogen-activated protein kinase/ERK signaling pathway, and apoptotic markers. Resveratrol significantly reduced the temozolomide resistance of U251/temozolomide cells, lowering the IC50 from 91.89 to 24.5 µM. Combined treatment demonstrated enhanced apoptotic cell death, significant downregulation of P-gp expression and activity, suppression of the mitogen-activated protein kinase/ERK signaling pathway, and upregulation of tumor suppressor miR-647. Resveratrol demonstrates potential as an adjuvant therapy by sensitizing temozolomide-resistant glioblastoma cells through multiple molecular mechanisms. It offers a promising approach to overcome chemotherapeutic resistance.

The study aims to develop an environmentally friendly method of producing silver nanoparticles using an extract from Bombax ceiba stem bark (Bc-AgNPs) and to investigate their potential medical applications, such as preventing blood cell damage, combating oxidation, and lowering inflammation. The synthesized Bc-AgNPs were characterized using UV-visible spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy, and transmission electron microscopy (TEM). The zeta potential examination revealed a highly stable colloidal solution of Bc-AgNPs with a surface charge of-14 mV. The synthesized Bc-AgNPs had a face-centred cubic structure with a crystalline size of 26 nm and an average grain size of 59.8 nm, as seen in the TEM images. Bc-AgNPs showed no hemolysis at varied concentrations, but B. ceiba stem bark extract at 100 µg/mL caused 16.8±1.9% hemolysis, and Triton X-100 (0.1%; positive control) caused 99.1±0.4% hemolysis. B. ceiba's aqueous extract contained flavonoid and phenolic components, which enhanced Bc-AgNPs' antioxidant capacity. The relative IC50 values were 28.03±0.98 µg/mL and 33.7±0.38 µg/mL. When compared to a reference medication, Bc-AgNPs demonstrated a moderate antiinflammatory effect, with IC50 values of 42.26±0.74 µg/mL for BSA and 50.93±1.07 µg/mL for egg albumin assay. According to the study, bio/hemocompatible Bc-AgNPs may be a viable treatment choice for antiinflammatory and antioxidant treatments.

Acne vulgaris, a prevalent inflammatory skin condition, impacts both appearance and quality of life, especially in adolescents. This study explores a novel treatment combining black seed oil, rosehip oil, and retinol within a nanoemulsion to improve therapeutic efficacy, drug delivery, and patient compliance while minimizing side effects.A nanoemulsion incorporating black seed oil, rosehip oil, and retinol was developed and characterized. Antimicrobial activity was evaluated via in vitro assays, while anti-inflammatory potential was assessed using standard models. HaCaT cell lines were used to determine cell viability. The formulation's performance was compared with commercially available Retino AC gel, focusing on stability, penetration, and overall effectiveness.The nanoemulsion showed strong antimicrobial effects against acne-related microbes, reduced inflammatory markers, and preserved high cell viability, confirming its biocompatibility. The combined action of black seed oil's anti-inflammatory and antioxidant properties, rosehip oil's sebum-regulating effects, and retinol's ability to promote cell turnover enhanced overall therapeutic outcomes. Compared to Retino AC gel, the nanoemulsion demonstrated superior efficacy, stability, and potential for better patient adherence.This study presents a synergistic, nature-based, and nano-enabled approach to treating acne and scars. The nanoemulsion offers a promising alternative to conventional therapies by improving effectiveness and safety. These results support further clinical development and highlight the potential of combining natural ingredients with advanced delivery systems for managing acne vulgaris.

Previously, diosgenin, a steroidal saponin, has demonstrated therapeutic potential for osteosarcoma. However, the underlying mechanisms still remain unknown.This study was designed to investigate the impact of diosgenin on methotrexate-mediated apoptosis in Saos-2 cells, specifically related to DNA damage.To assess the cell vitality of Saos-2 cells, we treated them with methotrexate, diosgenin, and a mixture of both, then performed the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide technique. Western blot was used to evaluate DNA damage by measuring the expression of γ-H2AX protein. The ELISA method was also applied to find the quantity of 8-oxo-2'-deoxyguanosine, and flow cytometry was used to analyze apoptosis.Combining methotrexate with diosgenin led to a major reduction in cell proliferation rate compared to monotreatments (p<0.05). This combination significantly increased apoptosis, measured by flow cytometry, and increased levels of γ-H2AX protein and 8-oxo-2'-deoxyguanosine.Diosgenin significantly augmented methotrexate-mediated apoptosis in Saos-2 cells through enhanced DNA damage mechanisms. These findings suggest that diosgenin could serve as a promising adjuvant therapeutic agent to improve the efficacy of current methotrexate-based chemotherapy regimens in osteosarcoma treatment, potentially reducing required drug doses and minimizing associated toxicity while maintaining therapeutic effectiveness.

This review offers an in-depth evaluation of Lasmiditan, a novel and selective 5-HT1F receptor agonist, representing a significant breakthrough in migraine pharmacotherapy. Unlike existing reviews, this article consolidates all critical aspects of Lasmiditan into a single, authoritative source encompassing both extensive literature analysis and original findings from our laboratory to provide researchers and clinicians with streamlined access to essential data and minimize the need for exhaustive literature searches.The review provides a comprehensive assessment of Lasmiditan, highlighting its physicochemical properties, pharmacological profile, mechanism of action, clinical efficacy and safety, drug interactions, and emerging insights from cell line studies. Lasmiditan's solubility influences its bioavailability and efficacy. It acts centrally without vascular constriction, unlike traditional therapies. Clinical trials confirm its rapid, effective migraine relief with mild side effects. Minimal drug interactions support its use in polypharmacy. Cell studies reveal its receptor activity and transport mechanisms, enhancing therapeutic understanding.Lasmiditan represents a groundbreaking addition to migraine therapeutics, providing a targeted, non-vasoconstrictive alternative. Its safety, tolerability, and efficacy make it a strong alternative for patients unsuitable for traditional treatments, with ongoing research likely to expand its clinical relevance.

Maternal stress during pregnancy has profound effects on offspring, disrupting brain development and behaviour. Mirtazapine, an antidepressant commonly prescribed for maternal depression, has an unclear impact on offspring neurophysiology and behaviour. We hypothesized that maternal mirtazapine treatment during pregnancy and lactation would influence locomotor activity, exploratory behaviour, and hippocampal synaptic plasticity in rat offspring, particularly in the context pre-gestational stress.Offspring from control or chronically stressed dams, treated with either vehicle or mirtazapine, were assessed. Behavioural responses were evaluated using the open field test, and the hippocampus was examined electrophysiologically to measure population spike (PS) amplitude of compound action potential, field excitatory postsynaptic potential (fEPSP) slope, short-term plasticity, and long-term potentiation (LTP).Maternal stress significantly reduced exploration of the central zone, indicating increased anxiety-like behaviour, although post hoc comparisons did not reach significance. Mirtazapine treatment did not reverse these behavioural alterations. PS amplitude was unaffected across groups, but fEPSP slope was significantly reduced in stressed offspring, with no recovery observed following mirtazapine treatment. Paired-pulse ratios across inter-pulse intervals (10-100 ms) were consistently decreased in the stressed group, indicating impaired short-term synaptic plasticity, which mirtazapine did not restore. In contrast, LTP showed a significant stress×treatment interaction (p=0.0201), suggesting that mirtazapine selectively enhanced long-term plasticity in stressed offspring.Mirtazapine did not reverse behavioural impairments or basal synaptic transmission deficits induced by maternal stress. It may selectively enhance long-term synaptic plasticity, suggesting its potential to modulate specific neurodevelopmental outcomes following prenatal stress exposure.

We investigated, in vivo, the chemopreventive efficacy of sinapic acid, as a known radical scavenger and antioxidant on mortality and toxicity in a N-ethyl-N-nitrosourea (ENU)-induced chronic lymphocytic leukemia (CLL) model in mice.Mice were divided into three groups: control (normal saline), ENU (80 mg/kg, i.p., single dose on day 31), and sinapic acid+ENU (pretreated with 30 mg/kg of sinapic acid, i.p., daily for 30 days, followed by 80 mg/kg of ENU). Body weight changes and mortality were monitored over 120 days. After this period, the animals were sacrificed, and lymphocytes, the target cells in CLL, were isolated and evaluated for various cellular parameters.Sinapic acid significantly (P<0.001) increased mouse survival up to 71%, delayed time of death, and prevented weight loss following ENU exposure. Additionally, sinapic acid inhibited the formation of reactive oxygen species (ROS) (P<0.001), lysosomal and mitochondrial dysfunction (P<0.001), and lipid peroxidation (P<0.05) in the isolated lymphocytes. These findings indicate a protective effect of sinapic acid against ENU-induced lethal toxicity.This study confirms that sinapic acid may serve as a promising chemopreventive agent against carcinogenicity induced by alkylating agents, primarily through the inhibition of oxidative stress and lysosomal/mitochondrial dysfunction.

The aim of this study was to evaluate hepatobiliary disorders adverse events associated with pembrolizumab by using the Food and Drug Administration Adverse Event Reporting System (FAERS).We collected FAERS data from the first quarter of 2009 to the third quarter of 2024 and used reporting odds ratio (ROR) to detect pembrolizumab-associated hepatobiliary adverse events (AEs). A signal was considered significant when the lower limit of the 95% confidence interval (CI) of the ROR exceeded 1, and≥5 AEs were reported. Serious and nonserious cases were compared by statistical analysis, and signals were further prioritized using a rating scale.A total of 20,225,379 AEs were reported in the FAERS database, of which 45,774 AEs listed pembrolizumab as the 'primary suspected' drug. Pembrolizumab treatment was significantly associated with hepatobiliary disorders. Among these AEs, 101 signals were detected at the preferred term (PT) levels, and 56 of them were identified as significant signals by using disproportionality analyses. The median time-to-onset (TTO) was 63 days. Notably, most hepatobiliary AEs occurred within three months after pembrolizumab therapy.Based on pharmacovigilance data from FAERS, different hepatobiliary AEs should be closely monitored and managed according to the indications for which pembrolizumab is used.

Fructosamine-3-kinase (FN3K), a deglycating enzyme originally studied in the context of diabetes, has recently emerged as a pivotal modulator of redox homeostasis and therapeutic resistance in cancer. FN3K catalyzes the removal of early glycation adducts, thereby stabilizing redox-sensitive proteins such as Nuclear factor erythroid 2-related factor 2 (Nrf2), a key transcriptional regulator of antioxidant defense. This review explores the evolving role of FN3K in tumor metabolism, highlighting its expression patterns across cancer types, structural features amenable to therapeutic targeting, and mechanistic interplay with the Nrf2 pathway. Emphasis is placed on FDA-approved drugs with FN3K-modulatory potential, evaluated through computational modeling, docking simulations, and structure - activity insights. The analysis reveals a dual opportunity: to repurpose redox-active agents as FN3K inhibitors and to exploit FN3K as a biomarker for redox stratification in precision oncology. Despite promising in silico data and preclinical correlations, challenges remain - particularly in achieving target selectivity, overcoming structural limitations, and validating pharmacodynamic markers. Addressing these barriers through integrated translational strategies could unlock FN3K as a tractable node in redox-driven cancer therapy.

Personalized medicine represents a paradigm shift in healthcare, aiming to tailor treatment strategies to the unique genetic, environmental, and lifestyle characteristics of individual patients. This approach holds immense potential for improving therapeutic efficacy and minimizing adverse drug reactions. With the rapid advancement of artificial intelligence, deep learning has emerged as a transformative tool in pharmacology, enabling precise modeling of complex biological data and uncovering hidden patterns in patient-specific information. This study investigates the application of deep learning techniques - such as Convolutional Neural Networks (CNNs), Recurrent Neural Networks (RNNs), Transformer architectures, and Generative Adversarial Networks (GANs) - in optimizing personalized treatment strategies. Using a diverse dataset comprising electronic health records (EHRs), genomic sequences, and clinical indicators, we developed and trained deep learning models for tasks including drug response prediction, biomarker identification, and adverse drug reaction (ADR) forecasting. Among the models evaluated, Transformer-based architectures demonstrated superior performance, achieving an accuracy of 91.2% and an AUC-ROC of 0.92 in drug response prediction tasks. Moreover, the integration of deep learning models into the treatment pipeline resulted in a 20-30% improvement in drug-patient matching efficiency compared to traditional statistical methods. The findings underscore the potential of AI-powered systems to enhance clinical decision-making and enable precision pharmacotherapy. However, challenges such as data privacy, model interpretability, and regulatory compliance remain critical barriers to widespread adoption. The study also explores future directions, including the implementation of explainable AI (XAI) and federated learning, to address these limitations and facilitate the integration of deep learning into routine clinical practice.