Search Results (12,643)

Biomolecules play pivotal roles in cellular signaling, metabolic regulation and the maintenance of physiological homeostasis in the human body, and their dysregulation is closely associated with the onset and progression of various human diseases. Consequently, the development of highly sensitive, selective, and stable detection platforms for these molecules is of significant value for drug discovery, pharmaceutical quality control, pharmacodynamic studies, and personalized medicine. In recent years, electrochemical biosensors, particularly those integrated with functional nanomaterials and biorecognition elements, have emerged as powerful analytical platforms in pharmaceutics and biomedical analysis, owing to their high sensitivity, exquisite selectivity, rapid response, simple operation, low cost and suitability for real-time or in situ monitoring in complex biological systems. This review summarizes recent progress in the electrochemical detection of representative biomolecules, including dopamine, glucose, uric acid, hydrogen peroxide, lactate, glutathione and cholesterol. By systematically summarizing and analyzing existing sensing strategies and nanomaterial-based sensor designs, this review aims to provide new insights for the interdisciplinary integration of pharmaceutics, nanomedicine, and electrochemical biosensing, and to promote the translational application of these sensing technologies in drug analysis, quality assessment, and clinical diagnostics. Full article

Background/Objectives: The development of small-molecule agents that selectively target DNA replication remains a central strategy in anticancer drug discovery. In this study, we report the biological characterization of a novel 6-nitro-benzodioxin-naphthalimide (NI) derivative (compound 5a), evaluated as a potential DNA-targeted anticancer lead. Methods/Results: The antiproliferative activity of 5a was assessed in a small panel of human lung carcinoma cell models (A549, H1299) and a non-malignant control (MRC-5), revealing pronounced cytotoxic effects in tumor cells, accompanied by favorable selectivity indices. Mechanistic investigations demonstrated that treatment with 5a results in strong inhibition of DNA synthesis, as evidenced by a marked reduction in EdU incorporation and a robust induction of the DNA damage marker γH2AX. These effects were associated with cell-cycle perturbations characterized by accumulation in G₁ and G₂/M phases, followed by activation of apoptotic pathways. Importantly, clonogenic survival assays confirmed that even transient exposure to 5a leads to a sustained loss of proliferative capacity, indicating irreversible long-term cellular damage. These results support a replication stress-driven mechanism of action for compound 5a, consistent with interference in DNA-associated processes during S phase. Conclusions: While the precise molecular initiating event remains to be elucidated, the observed biological profile positions 5a as a promising DNA-targeted lead structure with potential for further pharmaceutical optimization. These findings provide a solid foundation for the continued development of naphthalimide-based compounds as anticancer agents within a pharmaceutically relevant framework. Full article

Glioblastoma is one of the most highly aggressive types of brain tumor in adults. With limited treatment options, current therapies remain insufficient due to its invasiveness and immune evasion, highlighting the urgent need for new treatments. Bifunctional molecules targeting multiple aspects of the disease could be promising to overcome drug resistance and tumor heterogeneity. Metformin has demonstrated protective effects against brain tumors but requires high doses for efficacy, making it of great interest for molecular optimization. In this context, we synthesized a series of nine metformin–phenolic molecules, combining the metformin guanidine framework with phenolic acids, which have well-established properties in inhibiting cancer cell migration and adhesion. Their impact on cytotoxicity, reactive oxygen species inhibition, and signaling pathways was investigated for glioma cell lines and stem cells. Two of these hybrids, 5a and 5h, particularly enhanced cytotoxicity in glioblastoma cells, selectively targeting cancer cells while sparing healthy ones. Their mechanism of action differed significantly from metformin. Unlike metformin, which mainly triggers metabolic stress, the hybrids broadly inhibit RTK–MAPK–PI3K signaling, leading to cell cycle arrest and apoptosis. The results suggest that these compounds could offer a more effective and synergistic approach for glioblastoma treatment. Full article

Real-valued inter-residue distance maps provide essential spatial information for understanding protein folding mechanisms and guiding downstream applications such as function annotation, drug discovery, and structural modeling. However, existing prediction methods often struggle to capture long-range dependencies and to maintain topological consistency across different structural scales. To address these challenges, we propose a novel prediction framework that integrates a Mamba architecture, based on a selective state space model, to effectively model global interactions, and incorporates the Kolmogorov–Arnold Network (KAN) to enhance nonlinear structural representation. Extensive experiments on standard benchmark datasets, including CASP13, CASP14, and CASP15, demonstrate prediction accuracies of 86.53%, 85.44%, and 82.77%, respectively, outperforming state-of-the-art approaches. These results indicate that the proposed framework substantially improves the fidelity of real-valued distance prediction and offers a promising tool for downstream structural and functional studies. Full article

Currently, commercially available pain medications can cause adverse effects. Within this framework, researchers have been exploring new drug candidates derived from animal venoms and toxins. The objective of this study was to investigate the number of molecules with potential for pain relief derived from animal venoms and toxins, which could potentially contribute to the development of new biopharmaceuticals. We conducted a literature search in January 2025, covering the period from 1960 to 2025, in two Latin American and nine international scientific databases. The results consisted of 212 articles selected for review. From these articles, 152 toxins and venoms with analgesic potential were identified and classified into 14 different types of pharmacological targets. The peptides investigated, with masses between 500 Da and 5000 Da, are strong candidates for alternative biopharmaceuticals. Most of the toxins found interact with ion channels, representing an alternative to commercially available drugs. Full article

Maintaining cardiovascular stability during anesthesia is essential, yet the routine use of atropine to prevent vagally induced low heart rate may impose additional stress on the heart. This randomized, controlled, observer-blinded, clinical study aimed to evaluate whether ondansetron, a selective 5-HT₃ receptor antagonist, could serve as an alternative anesthetic adjuvant to modulate autonomic activity while maintaining cardiovascular stability in dogs. A total of 66 female dogs, with a mean age of 1.5 years and a mean weight of 16–18 kg ASA I, undergoing elective surgery were assigned to three study groups to receive atropine, ondansetron, or no autonomic-modulating drug. Heart rate, arterial pressure, respiratory rate, and NT-proBNP were recorded before, during, and after anesthesia. Dogs treated with ondansetron maintained stable cardiovascular values throughout the procedure, with no episodes of low heart rate or excessive increases in heart rate. In contrast, atropine induced marked and sustained elevation in heart rate and higher arterial pressures. Concentrations of the cardiac biomarker NT-proBNP increased significantly 48 h after surgery in the atropine group but remained unchanged in the ondansetron group, indicating the absence of additional myocardial stress. These findings suggest that ondansetron may help preserve autonomic balance during anesthesia while minimizing myocardial stress. Ondansetron could represent a useful component of multimodal anesthetic protocols, particularly in dogs in which excessive cardiac stimulation should be avoided. Full article

Drug resistance is an important challenge in medical research and clinical practice, posing a serious threat to the effectiveness of current therapeutic strategies. Transcriptomics has played a crucial role in analyzing resistance-related genes and pathways, while the application of machine learning in high-throughput data analysis and prediction has also opened up new avenues in this field. However, existing studies mostly focus on a single drug or specific categories, and their conclusions are limited in applicability across drug categories, while studies on drugs beyond antibacterial and antitumor categories remain limited. In this study, we systematically analyzed the transcriptomic data of resistant cell lines treated with 1738 drugs spanning 82 categories and identified core genes through an integrated analysis of three classical machine learning methods. Using the antibacterial drug salinomycin as an example, we established a resistance prediction model that demonstrated high predictive accuracy, indicating the significant value of the selected core genes in prediction. Meanwhile, some of the core genes identified through the protein–protein interaction (PPI) network overlapped with those derived from machine learning analysis, further supporting the reliability of these core genes. Pathway enrichment analysis of differential genes revealed potential resistance mechanisms. This study provides a new perspective for exploring resistance mechanisms across drug categories and highlights potential directions for resistance intervention strategies and novel drug development. Full article

Background: Direct oral anticoagulants (DOACs) are now the preferred anticoagulant over vitamin K antagonists for patients with atrial fibrillation (AF) and venous thromboembolism (VTE). Variability in drug exposure raises concerns about bleeding and thrombotic events, highlighting the potential value of therapeutic drug monitoring (TDM). Methods: This systematic review and meta-analysis conducted a systematic search of PubMed, Embase, Web of Science, Scopus, Cochrane Library, and ClinicalTrials.gov (from inception to May 2025) and identified studies reporting DOAC levels and clinical outcomes. Two reviewers independently performed screening, data extraction, and risk-of-bias assessment (RoB 2.0, Newcastle–Ottawa Scale). Random-effects meta-analytical models generated pooled estimates, with meta-regression exploring potential sources of variability (DOAC type, drug levels) and exposure–response relationships. Results: Nineteen studies comprising 5770 patients were included in the review. The pooled event rates were 8% for major bleeding (95% CI: 0.05–0.11), 7% for thrombotic events (95% CI: 0.05–0.09), and 3% for mortality (95% CI: 0.03–0.04). Heterogeneity was substantial for bleeding and thrombotic events (I² = 95.6% and 87.3%, respectively) but negligible for mortality (I² = 0%). Meta-regression analyses showed no significant association between mean DOAC concentration and either major bleeding (β = −0.00021, p = 0.35, Adj R² ≈ 0%) or thrombotic events (β = 0.00005, p = 0.78, Adj R² ≈ 0%), indicating that variations in measured plasma levels did not meaningfully explain event rate differences across studies. Conclusions: In this systematic review and meta-analysis, measured DOAC concentrations show limited and inconsistent association with clinical outcomes. While the present synthesis does not demonstrate a statistically robust linear correlation between DOAC plasma concentrations and adverse outcomes, it highlights the multifactorial determinants of bleeding and thrombosis risk underscores the potential value of selective TDM in individualized care. Further prospective, standardized studies are needed to define clinically actionable thresholds and to validate TDM-guided strategies that optimize the delicate balance between safety and efficacy in DOAC therapy. Full article

The management of lung cancer (LC) in patients with interstitial lung diseases (ILDs) presents significant challenges, particularly with the increasing use of immunotherapy (IT). Immunotherapy-related pneumonitis (ICIP) is a potential complication of immune checkpoint inhibitors (ICIs) that can be difficult to differentiate from pre-existing or treatment-induced ILD. The incidence of treatment-related pneumonitis is higher in patients with pre-existing ILD, which complicates the therapeutic approach. Moreover, antifibrotic drugs have shown potential in reducing the incidence of post-operative acute exacerbations in IPF patients undergoing surgery and radiotherapy. ILDs in LC patients can either develop ab initio, linked to environmental exposures, autoimmune diseases, or emerge because of cancer therapies. Although large-scale clinical trial evidence remains limited, careful therapy selection, early detection of pneumonitis, and close monitoring are crucial. Further prospective studies are needed to refine therapeutic strategies, particularly regarding the role of IT in this sensitive population and the role of combination therapies with antifibrotics and ICIs to optimize outcomes for patients with both LC and ILDs. This review summarizes the available evidence on the safety and efficacy of IT in this population, emphasizing the importance of personalized treatment approaches and vigilant monitoring. Full article

Lung cancer in never-smokers (LCINS) represents a distinct clinical entity driven by dominant oncogenic alterations and characterized by a low tumor mutational burden. Although tyrosine kinase inhibitors (TKIs) achieve high initial response rates, their long-term efficacy is limited by suboptimal pharmacokinetics, restricted central nervous system (CNS) penetration, tumor microenvironment barriers, and acquired resistance. In this review, we critically assess the current state of nanotechnology-assisted drug delivery systems for LCINS, with a primary focus on how rationally designed nanocarriers can overcome biological barriers, enable molecular subtype-specific therapeutic strategies, and address mechanisms that limit clinical efficacy and durability of response. We conducted a structured literature search using PubMed and Web of Science (January 2022 to November 2025), focusing on primary studies reporting the preparation, physicochemical properties, and therapeutic performance of nanocarriers in in vitro and in vivo models, as well as available pharmacokinetic and clinical data. LCINS is characterized by inefficient vasculature, high extracellular matrix density, active efflux transporters, and immunosuppressive niches, and is frequently complicated by brain metastases. Nanocarrier-based platforms can enhance aqueous solubility, prolong systemic circulation, and improve tumor or CNS targeting. Co-delivery systems combining TKIs with nucleic acid-based therapeutics, together with stimuli-responsive platforms, offer the potential for simultaneous modulation of multiple oncogenic pathways and partial mitigation of resistance mechanisms. In summary, nanotechnology provides a promising strategy to improve both the efficacy and specificity of targeted therapies in LCINS. Successful clinical translation will depend on biologically aligned carrier–payload combinations, scalable and reproducible manufacturing processes, and biomarker-guided patient selection. Full article

Melanoma was once considered ‘incurable’; however, drug therapy for the condition has dramatically transformed with the advent of immune checkpoint inhibitors and molecular targeted therapies. In this review, we summarize the published literature on melanoma drug therapy, presenting the current landscape of melanoma treatments, and discuss potential future transformations in melanoma therapy. Although the prognosis of advanced-stage melanoma had been extremely poor in the past, new-age immunotherapy has made long-term survival possible. Several immunotherapies and their combinations, as well as personalized vaccines, cell therapies, and intratumoral agents, have been tested with success; however, adverse toxicities have also been detected. Therefore, patient selection and management are critical. Furthermore, new approaches to overcome the limitations of the current treatments are also being developed. To implement these therapies clinically, guideline-recommended treatment algorithms should be followed while optimizing the therapies by considering factors such as presence of BRAF mutations which may lead to treatment resistance, increased disease burden/progression rate, toxicity tolerance, and the presence of brain metastases. In practice, the choice of the initial therapy should depend on the patient, leading to personalized therapy and minimal adverse effects. Full article

Imidazole is, from a structural point of view, a heterocycle consisting of three C atoms and two N atoms, belonging to the class of diazoles, having two N atoms at the first and third positions in the aromatic ring. Being a polar and ionizable aromatic compound, it has the role of improving the pharmacological properties of lead molecules, thus being used to optimize their solubility and bioavailability. Imidazole is a constituent of many important biological compounds, like histidine, histamine, and purine compounds, the most widespread heterocyclic compound in nature. In current practice, substituted imidazole derivatives play a major role in antifungal, antibacterial, anti-inflammatory, CNS active compounds, antiprotozoal, as well as anticancer therapy. Thus, imidazole derivatives have demonstrated significant anticancer activities by inhibiting the key metabolic pathways essential for tumor cell growth and survival. Nitroimidazoles, for instance, have been employed as hypoxia-directed therapeutic agents, targeting oxygen-deprived tumor tissues, while mercaptopurine derivatives are well-established in oncological treatments. Structural modifications of the imidazole nucleus have led to the novel compounds exhibiting increased selective cytotoxicity against cancer cells, while sparing normal healthy cells. In accordance with what has been stated, this review highlights recent research on the medicinal and pharmaceutical interest of novel imidazole derivatives, emphasizing their potential in the development of new drugs. Full article

The administration of various medications can induce bone loss as an adverse effect and may result in drug-induced osteoporosis, an important and clinically relevant form of secondary osteoporosis associated with an increased fracture risk. This review summarizes the skeletal effects of selected commonly used drugs with respect to bone metabolism, bone mineral density, and fracture outcomes. Medications may exert direct effects on osteoblasts and/or osteoclasts, leading to impaired bone remodeling and reduced bone mass. Alternatively, indirect mechanisms may contribute to skeletal damage, including disturbances in calcium and vitamin D metabolism with subsequent secondary hyperparathyroidism, as well as therapy-induced hypogonadism. Drug classes frequently associated with drug-induced osteoporosis during long-term use include glucocorticoids, aromatase inhibitors, androgen-deprivation therapy, thyroxine, proton pump inhibitors, anticoagulants (heparin and vitamin K antagonists), antidepressants, neuroleptics, and thiazolidinediones. Importantly, this overview represents a selection of relevant agents and does not aim to provide an exhaustive list. When prescribing potentially bone-damaging medications over extended periods, particularly in older individuals, bone health should be proactively considered. Evaluation should include laboratory assessment, fracture risk estimation (e.g., FRAX^®), and bone mineral density measurement when appropriate. Adequate calcium and vitamin D intake should be ensured, and guideline-based osteoporosis therapy initiated when indicated. Full article

Background/Objectives: Trigeminal Neuralgia (TN) is a chronic neuropathic condition characterized by sudden, severe facial pain. Anticonvulsants are the cornerstone of pharmacological management, yet comparative evidence based on pharmacological class remains scarce. This systematic review aimed to evaluate the efficacy and safety of anticonvulsants in TN, stratified by their mechanism of action. Methods: A systematic search in PubMed, Scopus and Web of Science was conducted following PRISMA 2020 guidelines. Studies employing a pharmacological approach including human patients with TN, published in English since 2000, were included. Risk of bias was assessed using the Cochrane RoB 2, the ROBINS-I and the ROBINS-E tools, according to the study design. Results: Out of 922 initial records, 12 studies met the eligibility criteria. Sodium channel inhibitors showed high efficacy but frequent adverse effects, particularly hyponatremia and central nervous system symptoms. Calcium channel modulators offered a more favorable safety profile. Combination therapies showed benefits, levetiracetam and topiramate were moderately effective and well tolerated. Although the evidence has limitations, anticonvulsants continue to be the primary treatment for TN. Sodium-channel blockers demonstrate strong efficacy, whereas alternative agents generally provide superior tolerability. Conclusions: These findings support selecting drugs according to their underlying mechanisms of action. Equally important is tailoring therapy to pain phenotype and patient characteristics, balancing mechanism with tolerability and efficacy. Full article

The growing prevalence of multidrug-resistant (MDR) Candida spp. necessitates the development of new antifungal strategies. Photodynamic therapy (PDT), already widely used in the treatment of various oral infections, is based on the synergistic interaction of three key elements: a photosensitizer capable of selectively binding to microbial cells, a light source with the appropriate wavelength, and the presence of molecular oxygen. This interaction results in the production of singlet oxygen and reactive oxygen species, responsible for the selective destruction of microorganisms. In recent years, numerous natural compounds have been explored as potential photosensitizers. Olive oil, a cornerstone of the Mediterranean diet, was recently recognized by the U.S. Food and Drug Administration as a medicinal substance thanks to its soothing, immunomodulatory, and antimicrobial properties, which have also been documented in regard to oral administration. Materials and Methods: The aim of this in vitro study was to evaluate the efficacy of activated olive oil as a novel photosensitizer in PDT against Candida species. Oral MDR clinical isolates of C. albicans, C. krusei, and C. glabrata were analyzed using the Kirby–Bauer method according to EUCAST protocols. Six different experimental conditions were considered for each strain: (i) 100 μL of extra-virgin olive oil (EVOO); (ii) 100 μL of EVOO pre-activated with 3% H₂O₂ (EVOO-H); (iii) 100 μL of EVOO irradiated for 5 min with polarized light (480–3400 nm, 25 W); (iv) 100 μL of EVOO-H subjected to the same polarized light; (v) 100 μL of EVOO irradiated for 5 min with a 660 nm diode laser (100 mW); and (vi) 100 μL of EVOO-H irradiated with the same laser. All plates were incubated at 37 °C for 48 h. Results: The results showed a variable response among the different Candida species. C. glabrata showed sensitivity to all experimental conditions, with a 50% increase in the diameter of the inhibition zone in the presence of polarized light. C. krusei showed no sensitivity under any of the conditions tested. C. albicans showed antifungal activity exclusively when EVOO-H was activated by light. In particular, activation of EVOO and EVOO-H with polarized light resulted in the largest inhibition zones. Conclusions: In conclusion, olive oil, both alone and pre-activated with hydrogen peroxide, can be considered an effective photosensitizer against drug-resistant Candida spp., especially when combined with polarized light. Full article