Current pharmaceutical design最新文献

Background: 3D bioprinting is a rapidly evolving technology in healthcare, especially in the fields of regenerative medicine, pharmaceutical research, and tissue engineering. This technique utilizes bioinks to fabricate three-dimensional structures that replicate the architecture and function of natural tissues through layer-by-layer additive manufacturing. This review aims to explore the current advancements, challenges, and future directions of 3D bioprinting.

Methods: A comprehensive review of the literature was conducted, focusing on various approaches to 3D bioprinting, including biomimicry, scaffold-based, scaffold-free, autonomous self-assembly, organ-on-a-chip, and microtissue building block techniques. Additionally, advancements in bioink development and different bioprinting technologies such as inkjet, extrusion, laser-assisted, stereolithography, acoustic, and magnetic bioprinting were analyzed.

Results: The literature highlights significant progress in bioprinting technologies, demonstrating the transition of 3D bioprinting from a theoretical innovation to a practical tool in tissue engineering and regenerative medicine. Advances in printing precision, cell-material interactions, and bioink formulations are bringing the technology closer to clinical applications.

Discussions: Key challenges remain-most notably creating robust vascular networks, scaling up production without loss of function, and ensuring that engineered tissues integrate seamlessly with a patient's own biology. Still, the potential payoffs are enormous, from tailor-made implants and on-demand drug testing platforms to fully functional organ replacements.

Conclusion: 3D bioprinting stands poised to transform personalized medicine and regenerative therapies. Achieving this vision will require sustained, interdisciplinary efforts to refine printing methods, innovate bioink chemistry, and master tissue maturation.

Cancer remains a formidable global health challenge, necessitating innovative strategies to enhance therapeutic outcomes. Cyclodextrins (CDs), cyclic oligosaccharides with a unique hydrophilic exterior and a hydrophobic cavity, have emerged as versatile tools in drug delivery, offering solutions to challenges such as poor solubility, systemic toxicity, and non-specific targeting associated with conventional cancer therapies. This review highlights the critical role of CDs in revolutionizing oncological therapeutics by enhancing drug solubility, stability, and bioavailability through the formation of inclusion complexes. The structural adaptability of CDs enables the encapsulation of hydrophobic anticancer agents, minimizing toxicity and improving therapeutic indices. Advanced chemically modified derivatives, such as hydroxypropyl-β-cyclodextrin and sulfonated CDs, exhibit enhanced solubilization properties and targeted delivery capabilities, addressing key pharmacokinetic and pharmacodynamic challenges. Additionally, hybrid CD-based nanocarriers, combining CDs with nanoparticles and polymers, have demonstrated superior efficacy in controlled drug release and sitespecific delivery. This review provides an in-depth exploration of various CD types, their modifications, and their integration into next-generation drug delivery systems. It emphasizes their application in overcoming multidrug resistance, improving tumor specificity, and enabling personalized medicine approaches. By synthesizing recent advances, this article underscores the transformative potential of CDs in cancer therapeutics and outlines future research directions in this promising field.

Introduction: Acute Lung Injury (ALI) is a serious complication of many diseases and can progress to Acute Respiratory Distress Syndrome (ARDS) without intervention. The current study aimed to determine the effect of Maxing Kugan Decoction (MXKGD) on an Oleic Acid (OA)-induced rat model of ALI while also exploring the regulatory effects of MXKGD on the PI3K/AKT signaling pathway and gut microbiota.

Methods: Ultra-Performance Liquid Chromatography-Quadrupole-Time-of-Flight Mass Spectrometry (UPLC-QTOF/MS) was employed to determine the chemical ingredients of MXKGD. The therapeutic effects of different doses of MXKGD in treating OA-induced ALI were investigated using histopathology, ELISA assays, and immunofluorescence analysis. Additionally, network pharmacology and 16S rRNA sequencing were utilized to explore the underlying mechanisms of MXKGD in ALI treatment.

Results: Through UPLC-QTOF/MS analysis, a total of 104 compounds were identified in MXKGD, including flavonoids, alkaloids, triterpenoids, glycosides, organic acids, and cyclic peptides. Pharmacodynamic results demonstrated that MXKGD could mitigate histomorphological changes in OA-induced ALI, suppress inflammation and oxidative stress, while promoting the proliferation and differentiation of alveolar type II (AT II) cells to repair the alveolar epithelial-microvascular endothelial barrier. Network pharmacology, molecular docking, and subsequent experimental validation revealed that MXKGD upregulates the expression of p-PI3K and p-AKT proteins, thereby activating the PI3K/AKT signaling pathway. Furthermore, MXKGD rebalanced the disturbance of gut microbiota and associated metabolic levels of short-chain fatty acids (SCFAs) to regulate the inflammatory response.

Discussion: This study suggests that MXKGD exerts anti-inflammatory effects and protects the alveolar epithelial- microvascular endothelial barrier in ALI models by activating the PI3K/AKT signaling pathway and modulating the abundance of beneficial gut bacteria. However, further metabolomic experiments are required to confirm its precise mechanism of action.

Conclusion: The data indicate that MXKGD can effectively inhibit the development of ALI by reducing inflammation and regulating the balance of intestinal microbiota. MXKGD may serve as a potential new therapeutic option for treating ALI.

Introduction: Jiuzhuan Huangjing Pills (JHP) have been shown to exert therapeutic effects on metabolic dysfunction-associated fatty liver disease (MAFLD), with a stronger intervention effect than single herbs. The purpose of this study was to elucidate the chemical constituents and mechanisms of JHP and its raw materials, Polygonati Rhizoma (PR) and Angelicae Sinensis Radix (ASR), in the treatment of MAFLD.

Methods: Serum pharmacochemistry and metabolomics were performed to examine drug-derived and endogenous components in MAFLD rats. In addition, network pharmacology was used to predict the key active components and targets of JHP, PR, and ASR in MAFLD mitigation, followed by molecular docking. ELISA kits were used to detect the levels of LCAT, GPCPD1, NNMT, NMRK1, ADO, and CSAD in liver tissues, while Western blotting was applied to determine the expression of CYP7A1 and CYP27A1.

Results: A total of 22, 8, and 10 compounds from JHP, PR, and ASR, respectively, were identified in serum. Meanwhile, 15, 5, and 7 compounds from JHP, PR, and ASR, respectively, were detected in rat tissues. Moreover, 157, 131, and 114 differential metabolites involved in 27, 6, and 9 pathways were found to be altered by JHP, PR, and ASR, respectively. JHP, PR, and ASR regulated LCAT and GPCPD1 in glycerophospholipid metabolism. JHP and ASR regulated NNMT and NMRK1 in nicotinic and nicotinamide metabolism. JHP further regulated ADO and CSAD in taurine and hypotaurine metabolism, as well as CYP7A1 and CYP27A1 in primary bile acid biosynthesis. Ten components of JHP acted on 12 targets to regulate 12 pathways in MAFLD treatment. Three components of PR acted on seven targets to regulate four pathways, while five components of ASR acted on five targets to regulate three pathways. The binding energies between these drug-derived compounds and their targets were all less than -5 kcal·mol⁻¹.

Discussion: These findings provide a theoretical foundation for the clinical application of JHP in MAFLD and underscore the value of traditional Chinese medicine formulas in addressing complex metabolic diseases through synergistic regulation. However, the intervention effects of JHP-derived components on MAFLD and their potential mechanisms of action on specific targets and metabolites require further investigation.

Conclusion: Our study found that JHP was associated with more components, targets, and pathways, which may be the mechanisms of JHP synergism.

Background: Apixaban (APX) prevents stroke and systemic embolism in patients with nonvalvular atrial fibrillation, as well as venous thromboembolism, and is marketed in tablet form.

Objective/method: This review provides an overview of analytical methods for evaluating APX in pharmaceutical matrices, with a focus on the eco-efficiency of green and white analytical chemicals. Studies published over the past decade were critically assessed to identify methodological trends and evaluate greenness using established assessment tools.

Results: The manuscript presents more than 40 analytical methods from the last 10 years for the evaluation of APX in pharmaceutical matrices. More than 75% of them are HPLC, and the majority, approximately 44%, use acetonitrile as a solvent. All methods presented were evaluated for their greenness profile. On average, they presented two green quadrants according to the National Environmental Methods Index (NEMI), a score greater than 75 on the Analytical Eco-Scale (ESA) in 88% of cases, an Analytical GREEnness Metric (AGREE) score of approximately 0.64, and all obtained more than 60 points on the Blue Analytical Grade Index (BAGI). Although eco-efficient options for APX evaluation in pharmaceutical matrices exist, the choice must be aligned with the intended objective, analysis routine, team training, time, resources, and cost.

Conclusion: Therefore, continuous refinement of practices is essential to ensure that methods remain efficient, robust, and environmentally responsible.

Introduction: This study employed network pharmacology and molecular docking to investigate the mechanism of Inula helenium in treating liver cancer.

Methods: Active compounds and their targets were identified from Inula helenium using HERB and Swiss Target Prediction. After standardizing target names via UniProt, liver cancer-related genes were collected from GeneCards and OMIM. Venny 2.1 analysis yielded 57 overlapping targets. A PPI network was constructed with STRING 11.5, and functional enrichment analyses were conducted using DAVID. GO analysis revealed multiple biological processes, cellular components, and molecular functions, while KEGG analysis highlighted key pathways including chemical carcinogenesis, IL-17, and NF-κB signaling. Thirteen core targets (e.g., TNF, IL1B, PTGS2, GSK3B, and MAPK14) were identified, and molecular docking confirmed their strong binding with active compounds.

Results: Inula helenium may treat liver cancer by modulating targets such as TNF, PTGS2, GSK3B, and MAPK14, as well as pathways like IL-17, NF-κB, and hepatitis B, thereby suppressing tumor growth and apoptosis.

Discussion: The findings support the anti-hepatocellular carcinoma effect of Inula helenium and suggest potential mechanisms, though further clinical validation is needed due to inherent limitations of network pharmacology.

Conclusion: This study offers a theoretical basis for the clinical use of Inula helenium in liver cancer treatment and encourages further investigation.

Introduction: This study elucidates molecular mechanisms underlying sanguinarine (SAN)- mediated inhibition of Lung Adenocarcinoma (LUAD) progression.

Methods: Potential targets for SAN and LUAD were obtained from public databases. A Protein-Protein Interaction (PPI) network was constructed, and core targets were visualized using Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed with DAVID, while Reactome, WikiPathways, and MSigDB Hallmark analyses utilized Enrichr. Core targets expression and immune infiltration in LUAD were validated using The Cancer Genome Atlas (TCGA). Molecular docking assessed binding affinity between SAN and core targets, and in vitro experiments confirmed SAN's suppression of LUAD progression via the TGF-β1/Smad3 pathway.

Results: Ten core targets of SAN in LUAD were identified. GO analysis revealed biological processes including proliferation, apoptosis, and signal transduction. Significantly enriched cancer-related pathways included PI3K-Akt, MAPK, Ras, and TGF-β signaling, the latter of which was significantly enriched across KEGG, Reactome, WikiPathways, and MSigDB Hallmark analyses. Molecular docking demonstrated a strong binding affinity between SAN and core targets. In vitro, SAN suppressed proliferation and autophagy in A549 cells while promoting apoptosis by inhibiting the TGF-β1/Smad3 signaling pathway.

Discussion: The results demonstrate SAN's multi-target action against LUAD, notably through the inhibition of TGF-β1/Smad3, providing a mechanistic basis within oncogenic networks. Limitations include reliance on in vitro models and the preclinical focus. Future work requires in vivo validation and clinical translation.

Conclusion: This study identifies key targets and pathways for SAN's inhibition of LUAD progression, validating its effect through the suppression of TGF-β1/Smad3 and providing experimental evidence for clinical application in LUAD therapy.

Introduction: Myocarditis (MC) is an inflammatory cardiomyopathy with high morbidity and mortality. Current treatment options for MC have limitations and side effects, necessitating the exploration of new therapies. Traditional Chinese Medicine (TCM), particularly Huaiqihuang Granules (HQH), has shown promise due to its anti-inflammatory, antioxidative, and anti-apoptotic properties. However, the application in cardiovascular diseases remains underexplored.

Methods: We employed network pharmacology, molecular docking, and Molecular Dynamics (MD) simulations to evaluate HQH's effects on MC. This involved identifying bioactive components and therapeutic targets, conducting enrichment analyses, and performing molecular docking and MD simulations to validate the interactions between HQH components and MC-related targets.

Results: A total of 57 bioactive components in HQH and 143 potential therapeutic targets for MC were identified. Enrichment analyses revealed that HQH's potential treatment effects on MC involve various processes and pathways, including response to lipopolysaccharide, peptidase activity, the extracellular region, and pathways in cancer. Molecular docking indicates that Physalin A, sibiricoside A_qt, zhonghualiaoine 1, and methylprotodioscin_qt, along with ALB, PTGS2, AKT1, ESR1, and MMP9, may serve as key therapeutic components and targets. MD simulations confirmed strong interactions between HQH's core components and MC-related targets, supporting their potential therapeutic effects.

Discussion: This study suggests that HQH exerts therapeutic effects against MC through multi-target mechanisms and stable targets. These findings provide valuable insights into alternative treatment strategies for MC, offering a foundation for further research and clinical exploration.

Conclusion: This study confirms that HQH can influence MC through various active components and multiple therapeutic targets.

Background: Citrus reticulata (CR) has a long-standing role in traditional medicine, primarily due to its bioactive constituents such as hesperidin and narirutin, which are known for their antioxidant, antiinflammatory, antibacterial, and anticancer properties.

Objective: This study investigates the anti-proliferative activity of CR water extracts against DU-145 prostate cancer cells and explores the therapeutic potential and underlying molecular mechanisms of hesperidin and narirutin in prostate cancer (PCa) and benign prostatic hyperplasia (BPH) through network pharmacology and molecular docking approaches.

Methods: Cytotoxicity assays were employed to determine the anti-cancer efficacy (IC50) of processed CR water extracts in DU-145 cells. Targets related to hesperidin, narirutin, PCa, and BPH were identified using bioinformatics platforms. Network pharmacology was applied to construct compound-target interaction networks and perform enrichment analyses (GO, KEGG, and DisGeNET) to elucidate key signalling pathways. Molecular docking was conducted to validate compound-target interactions.

Results: Soil-processed CR extracts exhibited the strongest anti-cancer activity (IC50 = 1.789 mg/mL). Enrichment analyses identified significant pathways, including AGE-RAGE signalling, p53 signalling, inflammation, angiogenesis, and apoptosis. Molecular docking confirmed strong binding affinities of hesperidin and narirutin to the predicted targets.

Conclusion: Anti-proliferative assays, network pharmacology, and molecular docking collectively demonstrate that hesperidin and narirutin from CR show strong therapeutic potential against PCa and BPH. The findings highlight the involvement of AGE-RAGE and p53 signalling pathways and support the potential of these compounds in future drug development.

Iron deficiency (ID), with or without anemia, is a frequent and underrecognized condition among patients undergoing cardiac surgery, and it is associated with worse perioperative outcomes, including higher mortality, longer ICU and hospital stays, and increased transfusion requirements. This review summarizes current evidence on the prognostic role of ID and the effectiveness of supplementation strategies. While intravenous iron therapy has shown potential to improve hemoglobin levels and reduce transfusion needs, study results remain inconsistent, partly due to differences in timing, dosage, and formulations used. Newer oral agents and nanotechnology-based delivery systems offer improved bioavailability and tolerability, though clinical data in cardiac surgery remain limited. Overall, routine preoperative screening for ID using ferritin and Transferrin Saturation is essential, particularly in non-anemic patients, as timely supplementation may improve perioperative recovery. Intravenous administration remains the preferred method in moderate to severe cases. However, standardized protocols and further high-quality randomized trials are required to define the optimal management of iron deficiency in this high-risk population.