Assay and drug development technologies最新文献

Naotai formula (NTF) is clinically used for stroke treatment, yet its molecular mechanisms involving vascular and metabolic regulation remain unclear. This study combines network pharmacology (NP) and Mendelian randomization to explore NTF's therapeutic targets and pathways in stroke. Stroke-related genes were sourced from public databases, and NTF's active compounds were screened using SwissADME. Summary-data-based Mendelian randomization (SMR) analysis, combined with colocalization, integrated stroke genome-wide association study data with blood expression quantitative trait loci and protein quantitative trait loci datasets to identify genes/proteins causally linked to stroke risk. Protein-protein interaction (PPI) network and drug-compound-target networks were constructed using Cytoscape and R. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses identified functional roles. Molecular docking assessed interactions between key compounds and prioritized targets. A total of 579 overlapping genes linked NTF and stroke. SMR identified 44 stroke-associated genes, with vascular endothelial growth factor A, angiotensinogen (AGT), and lipoprotein(a) replicated. Validation in Brain-eMeta supported eight of these targets, supporting tissue relevance. Enrichment analyses highlighted pathways including PPAR signaling, cholesterol metabolism, and vascular function. Core targets (Adiponectin, C1Q and collagen domain containing (ADIPOQ), Scavenger Receptor Class B Member 1 (SCARB1), and AGT) emerged from PPI networks. Molecular docking confirmed strong binding between NTF's Calycosin and AGT, a key renin-angiotensin system protein. NTF likely mitigates stroke by modulating genes involved in cholesterol metabolism and vascular regulation. The predicted Calycosin-AGT interaction provides a genetically informed hypothesis for a possible role in renin-angiotensin modulation. This integrative approach provides genetic and mechanistic insights into NTF's therapeutic efficacy.

Drug delivery systems are now being advanced by integrating sophisticated nanotechnologies to enhance therapeutic efficacy. Tremendous advancement has been achieved in the field of cancer therapy through the utilization of hyaluronic acid-based nanocarriers, which are well-acknowledged for their capacity to transport medication precisely to targeted regions. Quantum dots exhibit unique optical properties that allow for precise drug administration and monitoring capabilities. Carbon nanotubes provide a large surface area and exceptional strength, allowing for precise manipulation of drug delivery patterns. Dendrimers are versatile structures that can transport many drugs simultaneously, whereas mesoporous silica-functionalized nanoparticles allow exact manipulation of the release rate of pharmaceuticals. Polymer-lipid hybrid nanoparticles synergistically integrate the durability of polymers with the compatibility of lipids, hence augmenting the availability of drugs within the body. Hexagonal boron nitride nanosheets are becoming more recognized as favorable carriers due to their biocompatibility and potential for tailored administration. These achievements demonstrate the changes happening in the field of pharmaceutical administration, where nanotechnology is used to tackle issues such as restricted bioavailability and unanticipated adverse effects. This ultimately enhances the effectiveness of medicines and improves patient outcomes. Future investigations will focus on improving these technologies for broader therapeutic applications.

Stroke is an intricate oxidative and inflammatory response resulting from cerebral ischemia followed by reperfusion injury. Complex pathophysiology of stroke poses challenges for treatment. Peroxisome proliferator-activated receptor (PPAR) expression in the rat hippocampus is markedly elevated post cerebral ischemia/reperfusion (I/R) injury. Hence, saroglitazar, a dual PPAR-α/γ agonist, was investigated against cerebral I/R injury in rats. Male Sprague-Dawley rats were subjected to bilateral common carotid artery occlusion for 30 min and reperfusion for 3 days. During the reperfusion, animals were treated with vehicle or saroglitazar once a day for 3 days. The behavioral parameters were assessed, and animals were sacrificed to measure oxidative markers (malondialdehyde, superoxide dismutase, catalase, and reduced glutathione), inflammatory markers (interleukin-6, tumor necrosis factor-α, nuclear factor kappa-light chain enhancer of activated B cells (NF-κB), and high mobility group box 1 (HMGB-1) protein, infarction, and histopathology changes. Following I/R injury, antioxidant enzymes were reduced, while nitric oxide and inflammatory markers were increased in the disease group. In the rat hippocampus, these changes led to neurobehavioral impairment and cerebral infarction. Saroglitazar improved the levels of antioxidants and reduced inflammation; 2,3,5-triphenyltetrazolium chloride stain and histopathological analysis revealed the neuroprotective effect of saroglitazar in the hippocampus region. The neuroprotective effects of saroglitazar were attributed to its activation of both PPAR-α and PPAR-γ. It improved antioxidant levels and inhibited proinflammatory cytokines by suppressing the HMGB-1/NF-κB signaling pathway. These findings underscore the potential of saroglitazar in mitigating cerebral I/R injury.

Diabetes management necessitates innovative approaches to enhance treatment efficacy and patient adherence. The study aimed to develop a transdermal patch loaded with emodin, hypothesized to provide a noninvasive treatment option that circumvents complications of oral administration. To optimize the formulation, a full factorial experimental design was employed, focusing on the concentrations of hydroxypropyl methylcellulose K15 and geraniol. Compatibility and mechanical characteristics were investigated using Fourier-transform infrared spectroscopy and differential scanning calorimetry. The patch's drug release profile was assessed via in vitro studies, while its stability was tested under accelerated conditions. The antidiabetic efficacy was evaluated in diabetic rats using an in vivo model. The optimized patch (batch SF7) released 94.57% of the drug over 12 h. Under accelerated stability conditions, the patch showed a minor decline in folding endurance from 396 ± 1.50 to 369 ± 2.63 folds and drug content uniformity from 98.70% ± 0.02% to 98.14% ± 0.23%. The in vivo antidiabetic study demonstrated a considerable decrease in blood glucose levels in SF7-treated rats from 245.83 ± 3.25 mg/dL to 120.86 ± 4.24 mg/dL over 12 h (p-value < 0.001), comparable with the standard drug glibenclamide. The emodin-loaded transdermal patch displayed consistent drug release, maintained stability, and demonstrated significant antidiabetic activity, suggesting that it is a promising noninvasive therapy for diabetes management.

This study aimed to enhance the therapeutic efficacy of prednisolone by developing a nanostructured lipid carrier (NLC) system for topical ocular administration and addressing the limitations of current topical therapy. Drug-loaded NLCs (prednisolone acetate [PSA1]-PSA13) were formulated using high-pressure homogenization techniques, optimized with a central composite design, and evaluated for various pharmaceutical properties. An optimization study indicates that the lipid ratio and surfactant concentration influence particle size, entrapment efficiency (EE), and drug release. The optimized NLC formulation (PSA3) was integrated into a pH-triggered in situ gel system and assessed for drug permeation, ocular irritation, and stability. The optimized drug-loaded NLC formulations (PSA3) exhibited a nano size of 96.80 ± 0.51 nm, achieving an EE of 84.51 ± 1.31% and a drug release rate of 95.76 ± 1.23%. The drug permeation through the goat cornea was significantly higher in the in situ gel (PSAG4) compared with the control (marketed PSA eye drop). Additionally, the eye irritation data indicated good ocular tolerance, while stability studies confirmed that the developed formulation remained stable at room temperature. In conclusion, the developed NLC-based in situ gel appears to be a promising approach to enhancing the efficacy of prednisolone in topical therapy for the successful treatment of ocular inflammation.

Automation plays a crucial role in enhancing efficiency and increasing capacity for in vitro absorption, distribution, metabolism, and excretion profiling in early drug discovery. Building an automation platform requires a careful balance of innovation and practical considerations to align assay needs with technological capabilities. In this study, we present a state-of-the-art automation system designed to support the miniaturization of the Caco-2 permeability assay from the 24-well to the 96-well format. This platform integrates advanced infrastructure for cell culture and assay execution, along with several key features, including innovative cleaning protocols, cutting-edge plate tracking, and dynamic scheduling capabilities. The fully automated 96-well platform delivers significant efficiency gains, increased capacity, and faster turnaround for permeability assay support while maintaining high predictive accuracy. It correctly classified 94% of 50 literature compounds, demonstrating strong concordance with the established 24-well format. Moreover, the platform enables large-scale permeability data generation, advancing our "predict-first" modeling paradigm, in which predictive models guide experimental design and compound prioritization.

Rheumatoid arthritis (RA) is a chronic inflammatory disease whose exact etiology is yet unidentified. Dexamethasone sodium phosphate (DSP) is an established anti-inflammatory agent, but its application is limited due to its dose-dependent toxicity. This can be minimized by targeting the delivery of DSP. Zinc oxide nanoparticles (ZnONPs) have potential in the management of RA owing to their anti-inflammatory and antioxidant characteristics. The aims of this research were to develop, optimize, and determine the cytotoxicity of FA decorated DSP loaded ZnONPs. The biogenic ZnONPs have been synthesized using Piper nigrum. The Zeta potential, particle size, PDI, and loading ability of DSP-Pn@ZnONPs were improved utilizing Box-Behnken design since these factors are crucial in preserving the pharmacokinetic behavior of nanoparticles. The FA-DSP-Pn@ZnONPs were characterized via UV-visible spectrophotometer, X-ray diffraction, energy dispersive spectrophotometer, scanning electron microscopy, TEM, FT-IR, Zeta analysis and H¹NMR. Nanoparticles exhibited minimal DSP release at 32.7207% at 7.4 pH (normal blood), but a substantial release of 88.72544% at 6.5 pH (RA synovial site) indicating its potential for targeting ability at the inflammatory site. Moreover, the various in vitro analyses include antioxidants, and anti-inflammatory. Furthermore, the release of FA-DSP-Pn@ZnONPs was accurately described by the Korsmeyer-Peppas model and exhibited a non-Fickian process, which was governed by both diffusion and erosion. The cytotoxicity ability and anti-inflammatory effects of NPs were determined using the MTT analysis method in non-lipopolysaccharide (LPS) and LPS-activated RAW 264.7. The FA-DSP-Pn@ZnONPs showed significant anti-inflammatory and anti-arthritis activities. At the highest concentration, it inhibited cell hemolysis and growth of the LPS-stimulated macrophage cell line, suggesting potential therapeutic interventions against RA.

This review examines the drug-like, cancer-suppressing, and food-based properties of paclitaxel, naringenin, and quercetin while emphasizing their therapeutic pathways and molecular functions. The chemotherapeutic agent paclitaxel stabilizes microtubules for cell cycle arrest, and naringenin alongside quercetin shows strong anticancer responses, antioxidant effects, and anti-inflammatory actions. The review explains how these compounds serve in cancer treatment together with their pharmacological mechanisms and it describes how novel drug delivery systems boost their therapeutic potential and bioavailability. Drug-testing evidence as well as patent documentation reveals increasing attention toward these drug compounds in cancer treatment. The three compounds paclitaxel, naringenin, and quercetin show great potential as cancer treatment and prevention agents while researchers continue to develop their clinical performance advanced through ongoing studies.

While sodium-glucose transporter 2 inhibitors (SGLT2i) demonstrate urate-lowering effects, their causal role in Gout prevention remains controversial. This study employs advanced Mendelian randomization (MR) techniques to dissect immune-mediated mechanisms underlying this relationship. Using bidirectional two-sample MR and mediation analysis, we analyzed genetic instrument variables for SGLT2i (10 single-nucleotide polymorphisms, F-statistic >20), Gout risk (6,810 cases/477,788 controls), and 731 immune cell phenotypes. Pleiotropy and heterogeneity were also assessed to ensure robustness. The study confirmed a significant indirect effect of SGLT2i, which exhibited a 2.6% reduced Gout risk (Odds Ratio [OR]: 0.9738, 95% confidence interval [CI] = 0.9623, 0.9854, P = 1.12e-05). Thirty-five immune cell phenotypes were identified as significantly affecting Gout development, with key phenotypes such as CD86 on myeloid Dendritic cell (DC) (OR: 0.9966; 95% CI = 0.9930, 0.9995), contributing to 12.8% of the overall mediation effect. No evidence of heterogeneity or pleiotropy was detected and reverse-direction MR corroborated these findings. Our study first established SGLT2i as Gout-protective agents through DC-mediated immunomodulation, offering mechanistic insights for targeted prevention strategies in clinical practice.