Current pharmaceutical design最新文献

Introduction: Keloid scars and hypertrophic scars both cause abnormal protrusions or depressions on the skin surface, some of which may develop noticeable discoloration that significantly affects aesthetic appearance, leading to psychological distress and impacting the patient's overall well-being. Currently, there are still no effective treatment methods available. Among the various mechanisms involved in scar treatment, most studies focus on regulating the activity of fibroblasts. However, current research also suggests that inflammation plays a significant role in the healing process of scars. Glycyrrhetic Acid (GA) is a natural sweetener found in licorice root and is widely used as a sweetening agent in various plants worldwide. In our previous studies, we found that GA exhibits potential anti-scarring effects in animals, but the underlying mechanisms remain unclear.

Methods: We employed a combination of animal experiments, transcriptomics, network pharmacology, molecular docking, and molecular dynamics simulations to explore potential mechanisms. The expression of relevant genes and proteins was validated through qRT-PCR and protein detection.

Results: The results showed that GA promotes scar healing in a dose-dependent manner. Compared with the model group, the GA treatment group inhibited the expression of inflammatory factors IL-6 and IFN-γ in rat scar tissue, down-regulated the expression of CDK1, a cell cycle-related protein, and the expression of MKI67, a proliferation marker.

Conclusion: Finally, we concluded that GA promotes the recovery of rat skin scars by regulating the balance of inflammation and fibroblast proliferation.

Introduction: To sustain systemic homeostasis, the gut microbiota manages immunological, metabolic, and inflammatory processes. Multiorgan diseases, especially those impacting the liver, kidney, and cardiovascular system through the hepato-cardiorenal axis, have been strongly associated with dysbiosis.

Methods: A comprehensive literature search was conducted using PubMed, Scopus, Web of Science, Science Direct, and Google Scholar, with the focus on articles till 2025. Eligible sources included clinical trials, systematic reviews, and peer-reviewed academic publications that discussed metabolites, gut microbiota, and treatment approaches for diseases of the liver, kidney, and heart. A qualitative synthesis of the data indicated important mechanisms and potential treatments.

Results: SCFAs have anti-inflammatory and intestinal barrier integrity-enhancing qualities, whereas uremic toxins and TMAO promote oxidative stress, fibrosis, and vascular dysfunction. Hepatic steatosis, insulin resistance, and systemic inflammation are all affected by the dysbiosis-induced bile acid imbalance. Microbiotatargeted therapies include fecal microbiota transplantation, fiber- or polyphenol-rich diets, probiotics, prebiotics, synbiotics, and pharmacological modification of bile acid or TMAO pathways, which have potential but need more comprehensive validation.

Discussion: The findings show that, among other factors, gut metabolites-such as uremic toxins, bile acids, TMAO, and SCFAs - are key players in mediating inflammation and metabolic dysregulation across the hepato-cardiorenal axis. However, the lack of consistent treatment protocols and differences in microbiome composition limit the practical application of preclinical research that has clearly demonstrated the existence of mechanistic links. Future research should focus on long-term clinical outcomes, biomarker identification, and precise microbiome modifications to establish causation and improve therapy effectiveness.

Conclusion: The gut microbiota significantly influences the hepato-cardiorenal axis through metabolitemediated signalling. While therapeutic modulation shows promise, precision medicine approaches and highquality randomized trials are essential to tackle multi-organ metabolic and inflammatory diseases.

Introduction: For centuries, Traditional Chinese Medicine has been a subject of extensive research for its healing properties, including its effects against viruses. The pollen of Typha angustifolia emerges as a notable natural source of antiviral agents, with earlier investigations focusing on its antioxidant and antiinflammatory properties, which are associated with flavonoids and phenolics that facilitate electron transfer. These bioactive compounds could potentially disrupt viral entry and replication, thereby necessitating further studies.

Methods: Molecular docking analysis was conducted on 11 compounds from T. angustifolia targeting the entry protein of dengue virus, the NS5B polymerase of hepatitis C virus, and the RdRp of Japanese encephalitis virus. The binding affinity was evaluated through LibDock score assessments, and simulations of molecular dynamics (RMSD and RMSF) were performed to analyze the stability of the complexes.

Results: Naringenin was consistently identified as one of the highest binders for all three viral proteins, achieving the top score for the RdRp of Japanese encephalitis (129.288). Isorhamnetin showed the greatest binding affinity for the hepatitis C NS5B polymerase (120.827), exceeding that of sofosbuvir (120.629), while isorhamnetin-3-O-rutinoside displayed strong binding to the dengue viral entry protein (97.0838). Molecular dynamics confirmed the stability of ligand-protein interactions, underlined by sustained van der Waals and electrostatic forces.

Discussion: These findings underscore naringenin as a versatile antiviral candidate, with other flavonoids exhibiting specific effectiveness that could facilitate multitarget inhibition approaches. This polypharmacological potential of flavonoids aligns with their established antiviral properties, although confirmatory experimental studies are critical.

Conclusion: Naringenin emerged as the most potent and reliable antiviral agent among the compounds of T. angustifolia, particularly against the RdRp of Japanese encephalitis. These computational insights validate T. angustifolia pollen as a promising natural antiviral resource, warranting further validation through in vitro and in vivo studies.

Introduction: Obesity represents a significant health and lifestyle issue worldwide. White and brown adipocytes, which originate from resident mesenchymal stem cells (MSCs), are critically involved in the process of adipogenesis.

Methodology: Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) were utilized to investigate epigenetic modifications associated with adipogenic differentiation. Briefly, histone acetylation and/or methylation pattern of hUCMSCs were evaluated with histone deacetylase inhibitor Trichostatin A (TSA) for cell viability, death rate, and adipogenic commitment.

Results: Inhibition of histone deacetylation was accompanied by a reduction of the global methylation pattern compared to the baseline levels in untreated cells. These changes decreased cell viability at 36 hrs, while reciprocally increasing the rate of cell death from 24 hrs. Most importantly, TSA-treated cells demonstrated diminished adipogenic differentiation compared to normal cells post-induction.

Discussion: Epigenetic remodeling triggered by inhibition of histone deacetylase led to reduced DNA methylation. The increased cytotoxicity, impairing cell survival due to alteration in chromatin state, reduced adipogenic differentiation potential in TSA-treated cells, promoting disruption of normal lineage commitment pathways.

Conclusion: Taken together, the results show a possible anti-obesity effect of histone deacetylation inhibitors (HDCAs) in MSCs, resulting in depletion and restriction of their adipogenic differentiation.

Introduction: Risankizumab has demonstrated remarkable efficacy in the treatment of psoriasis; however, its long-term use faces multiple challenges, including high costs, reduced efficacy over time, and potential safety concerns, such as infections and malignancies. Therefore, identifying potential alternative or adjunctive therapies to risankizumab has significant clinical importance.

Methods: We analyzed single-cell RNA sequencing data from mature dendritic cells (mDCs) and CD4⁺ T cells collected before risankizumab treatment and at days 3 and 14 post-treatment. Differential expression, cell communication analysis, pseudotime trajectory analysis, and transcription factor regulatory network analysis were performed. Small-molecule drug prediction was performed using the DsigDB database, and molecular docking was used to evaluate binding interactions between candidate drugs and their targets.

Results: We identified 15 key transcription factors (MAFB, IRF3, NFIC, SREBF1, ELF3, DLX5, MEF2A, MXD3, MAFF, MECP2, ERF, KLF9, RARA, KLF5, ZBTB2) that were significantly altered in CD4⁺ T cells during the early phase of risankizumab treatment in psoriasis, along with their downstream differentially expressed genes (including KRT14, S100A9, S100A8, S100A7, KRT6A, GJB2, CALML3, and KRT6B). Based on these core factors, five candidate small-molecule drugs with potential therapeutic value for psoriasis were predicted: alitretinoin, simvastatin, MS-275 (entinostat), colchicine, and (+)-chelidonine.

Discussion: This study characterized transcriptional regulation of CD4⁺ T cells and mDCs during early risankizumab treatment in psoriasis, predicting potential therapeutic targets and candidate small-molecule drugs from single-cell regulatory networks. Although promising, these results need further validation in larger cohorts and experimental models.

Conclusion: These findings offer preliminary clues for future risankizumab-based combination strategies in psoriasis.

Introduction: Nuciferine, the key aporphine alkaloid compound extracted from lotus leaf, has demonstrated remarkable effects in the prevention of obesity. Our current study sought to elucidate the exact mechanisms of the protective roles of nuciferine on obesity and associated metabolic abnormalities.

Methods: Male C57BL/6J mice were given a high-fat diet (HFD) containing 0.10% nuciferine for 12 weeks. Body weight and epididymal white adipose tissue (eWAT) mass were collected. Intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (IPITT) were conducted. A multidisciplinary approach, including transcriptomic analysis and network pharmacology, was employed to identify novel targets and signaling pathways of nuciferine in obesity prevention, which were further confirmed using real-time quantitative polymerase chain reaction (RT-qPCR), molecular docking, and in vitro cell experiments performed in RAW 264.7 macrophages.

Results: Nuciferine dramatically reduced the weight gain and eWAT mass and ameliorated glucose tolerance, insulin sensitivity, and inflammation in adipose tissue of HFD-fed mice. In fully differentiated 3T3-L1 adipocytes, nuciferine prevented palmitic acid (PA)-induced intracellular lipid accumulation, as evidenced by Oil Red O staining and triglyceride (TG) determination. Integration of transcriptomic sequencing in eWAT and network pharmacology identified 15 target genes, including LGALS3, CTSB, and RBP4, and 5 signaling pathways, including cAMP and Rap1 signaling pathways, which were primarily associated with inflammation. Further studies confirmed that nuciferine decreased LGALS3, CTSB, and RBP4 mRNA expression in eWAT of HFD-fed mice. Additionally, nuciferine inhibited mRNA expression of pro-inflammatory cytokines IL-6, along with LGALS3, CTSB, and RBP4 in lipopolysaccharide-treated RAW 264.7 macrophages. Molecular docking showed that nuciferine had strong binding ability to LGALS3, CTSB, and RBP4.

Conclusion: These findings suggest that nuciferine may reduce adipose tissue inflammation by inhibiting mRNA levels of macrophage inflammation-associated genes LGALS3, CTSB, and RBP4, thereby protecting against obesity and associated metabolic inflammation.

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.