Current pharmaceutical design最新文献

Introduction: Liposomes are bilayered vesicles capable of encapsulating both hydrophilic and hydrophobic compounds, making them widely used in pharmaceuticals and cosmetics due to their excellent biocompatibility and versatility. However, they are structurally vulnerable to additives, such as ethanol and surfactants, which are often unavoidable during formulation. Therefore, it is essential to evaluate the effects of these components on liposomal stability and release behavior.

Method: Second-order multiple linear regression models were developed to predict liposomal release based on ethanol and five Tergitol™ 15-S surfactant concentrations. Nonlinear interactions were visualized using 3D regression surfaces. Liposomal stability was classified into four categories using K-nearest neighbors, logistic regression, and stochastic gradient descent algorithms. All models were implemented in Python using Scikit-Learn and Matplotlib.

Result: All regression models demonstrated high predictive accuracy, with R² values of 0.9611-0.9899 and mean absolute errors (MAE) of 2.19%-5.44%. No overfitting was observed. Among the classification models, logistic regression achieved the highest test accuracy (87.98%), followed by SGD (80.12%) and KNN (80.88%).

Discussion: Tergitol concentration had a greater impact on liposomal release than ethanol. Surfactants with higher HLB values showed weaker interactions with the lipid bilayer, resulting in reduced release. This aligns with previous findings that highly hydrophilic surfactants have limited bilayer penetration. The models effectively captured nonlinear interactions and offer practical utility for formulation prediction.

Conclusion: This study evaluated the stability of liposomes under various concentrations of ethanol and Tergitol surfactants and classified them using machine learning algorithms. The developed models can be effectively applied to formulation design in liposome-based systems, including pharmaceutical and cosmetic applications.

Introduction: The primary goal in treating acute pain is to provide effective analgesia while minimizing the risk of progression to chronic pain. Opioids have long been the mainstay for treating moderate to severe pain. However, their use is increasingly questioned due to challenges such as addiction, tolerance, and adverse effects, including respiratory depression. A multimodal approach (balanced analgesia, multimodal analgesia- MMA), which includes non-opioid analgesic agents (NOAAs), adjuvant medications, and opioids, is recommended. This review was designed to cover the current characteristics and use of typical NOAAs, specifically nefopam and flupirtine, in contemporary practice.

Methods: A review search was conducted to abstract articles for analysis. All studies published in English from 1990 to 2025, mainly investigating NOAAs, specifically nefopam and flupirtine, were included. We used Google Scholar, PubMed, Scopus, Web of Science, EBSCO, and MEDLINE databases to extract articles. The findings of these articles were analyzed narratively to highlight mechanisms of action, indications, safety, and specific features.

Results: NOAAs may represent a viable alternative in contemporary analgesic treatments. Unlike opioids, centrally acting NOAAs do not carry the same risk of dependence and abuse, making them suitable alternatives for patients with acute and/or chronic pain. Recent studies provide valuable insights into these agents' evolving role in pain management. Typical NOAAs, such as nefopam and flupirtine, are associated with mild side effects, including nausea, dizziness, and anticholinergic symptoms, which may affect their acceptability in certain patient populations. Furthermore, their contraindications render them potentially dangerous for individuals with convulsive disorders or those taking specific medications, necessitating careful patient selection and clinical judgment.

Conclusion: Although these agents are beneficial in reducing opioid consumption, their use should be tailored to each patient, with careful follow-up. Patients receiving NOAAs should be monitored for adverse effects, particularly during treatment initiation. Monitoring is also essential for elderly patients and those with cardiovascular or neurological conditions to ensure safe administration. In conclusion, the clinical use of NOAAs requires careful consideration of potential adverse effects, contraindications, and drug interactions. Further well-designed studies are needed to better define these agents' characteristics, limitations, and comparisons with alternative pain management approaches.

Introduction: Ulcerative colitis (UC) manifests as persistent inflammation and ulceration within the mucosal and submucosal layers of the colon. The present study sought to elucidate the principal targets of Tongbian Baitouweng Decoction (TBD) in UC.

Methods: A total of 221 TBD-related and 1,270 UC-related genes were retrieved from public databases, with their intersection as candidate targets. Differential expression, machine learning, expression profiling, MR analysis, network construction, molecular docking, enrichment, and immune infiltration analyses were used to refine key targets and explore their functional associations with UC.

Results: PPARG, STAT1, and IL1B emerged as the principal targets of TBD against UC. Among UC samples, IL1B and STAT1 were upregulated, whereas PPARG was downregulated. MR analysis revealed significant causal associations: STAT1 (OR = 1.17), IL1B (OR = 0.50), and PPARG (OR = 0.97). A network comprising three targets and 53 corresponding active compounds was established, with molecular docking demonstrating strong binding affinities, particularly with quercetin. Enrichment analysis indicated that the three targets were jointly involved in pathways such as "Toll-like receptor signaling". Immune infiltration analysis revealed that IL1B and STAT1 correlated positively with activated CD4 T cells, macrophages, and natural killer cells, whereas PPARG displayed an inverse pattern.

Discussion: These findings align with existing evidence linking STAT1, PPARG, and IL1B to UC pathogenesis, highlighting TBD's therapeutic potential by targeting key inflammatory and barrier-regulatory pathways; future studies should validate these targets in preclinical models and explore the formula's clinical efficacy in large-scale trials.

Conclusion: STAT1, PPARG, and IL1B were TBD's key UC therapeutic targets, with regulatory roles providing a UC research mechanistic framework.

Introduction: Alzheimer's disease (AD) affects millions globally. This study explores the therapeutic mechanisms of Qingge Formula (QGF) against AD using network pharmacology and molecular docking.

Methods: Active components and targets were identified via TCMSP, Swiss ADME, and GeneCards databases. PPI networks, GO, and KEGG analyses were performed, followed by molecular docking.

Results: Core targets included PTGS2, EGFR, ESR1, STAT3, and SRC. GO identified 222 terms; KEGG revealed 65 pathways. Molecular docking revealed that the six key components bind to the core targets with energetically favorable conformations, among which SRC showed the highest affinity for all the Discussion: QGF likely modulates neuroinflammation, immunity, and synaptic plasticity pathways, with SRC as a crucial target.

Conclusion: QGF demonstrates multi-component, multi-target therapeutic potential against AD.

Introduction: This study systematically elucidates the anti-thrombotic material basis, potential targets, and molecular mechanisms of Equiseti hiemalis herba (EH) using an integrated strategy combining metabolomics, serum pharmacochemistry, network pharmacology, bioinformatics analyses, and molecular docking.

Methods: Components in the EH decoction were identified by UHPLC-MS. Sixteen normal male SD rats were administered EH to monitor weight and organ indices. Plasma metabolomics were used to analyze differential metabolites and pathways. Blood-absorbed prototype components were identified, and their targets were predicted. Network pharmacology was employed to intersect drug targets with thrombosis-related targets from GeneCards and an independent GEO dataset to identify core therapeutic targets. GO analysis and molecular docking were further used for validation.

Results: A total of 138 compounds, including caffeic acid, ferulic acid, and 13-docosenamide, were identified in EH. Administration to rats revealed only slight effects on the liver. EH primarily exerts its effects by modulating fatty acid, amino acid, and nucleotide metabolism. It acts on nine key targets (CA9, MAOA, TYMS, etc.) via 15 active components (gingerol, xanthosine, adenosine, etc.), influencing four pathways (glycine and serine metabolism, ammonia recycling, arginine and proline metabolism, pyrimidine metabolism) to achieve its anti-thrombotic effects. Importantly, the dysregulation of these nine key targets was significantly validated in an independent clinical venous thrombosis cohort from the GEO database.

Conclusion: This study proposes a multi-component, multi-target, and multi-pathway mechanism for EH against thrombosis and provides strong external clinical evidence supporting the disease relevance of the predicted targets. The findings offer a solid theoretical basis and valuable candidate resources for the future development of EH as an anti-thrombotic drug.

Guggulipids, lipid-soluble bioactives derived from the resin of Commiphora mukul, have gained increasing scientific attention for their diverse pharmacological properties. This review provides a comprehensive synthesis of current findings on the bioactivity, therapeutic potential, and advanced delivery systems of guggulipids. Beginning with a brief overview of their traditional medicinal significance, we outline key mechanisms of action, including modulation of lipid metabolism, modulation of anti-inflammatory pathways, antioxidant activity, and regulation of apoptosis. We examine preclinical and clinical evidence supporting the use of guggulipids in managing cardiovascular diseases, metabolic syndromes, and chronic inflammatory conditions. Special attention is given to recent innovations in drug delivery strategies, such as nanoparticles, proniosomal gels, and guggulosomes, which are designed to overcome the challenges of poor solubility and limited bioavailability. Additionally, emerging research avenues are discussed, including synergistic interactions with other phytochemicals and personalized medicine approaches. By integrating traditional knowledge with modern pharmacological insights, this review aims to guide future research and therapeutic applications of guggulipids in evidence-based medicine.

Tacrolimus (TAC) is recognized as a promising therapy for Dry Eye Disease (DED). Recent experimental studies indicate that TAC formulations, such as nanoemulsions and liposomes, notably improve tear production, stabilize the tear film, and reduce corneal damage in animal models. TAC achieves these effects by inhibiting T-cell activation and suppressing the production of inflammatory cytokines, primarily through the NF-κB signaling pathway. Clinical trials report that topical TAC, especially at 0.03% concentration, significantly alleviates both symptoms and signs in patients with Sjögren's syndrome and ocular graft-versushost disease. Critical clinical improvements include higher Schirmer test values, prolonged tear film break-up time, and decreased ocular surface staining. Comparative analyses suggest that TAC is at least as effective as cyclosporine and offers a favorable safety profile. Combining TAC with agents such as sodium hyaluronate may further enhance therapeutic outcomes. Despite the need for further studies to optimize dose and longterm safety, current evidence supports the use of TAC as an effective solution for individuals with refractory or severe DED, providing a vital option where conventional treatments may fail.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, marked by the accumulation of amyloid-β plaques and neurofibrillary tangles. Its incidence is rising as the global population ages. This narrative review explores the emerging interconnections among AD, circadian rhythms, and the immune system. The circadian system, governed by endogenous clocks, regulates key physiological processes and exhibits disruptions in the early stages of AD. Chronodisruption, disturbance of circadian rhythms, has been implicated in AD pathogenesis through its effects on metabolism, sleep, and neuroinflammation. The immune system also plays a central role in AD, with microglia and astrocytes contributing to disease progression. Immune function displays circadian variation, and disruptions in sleep and circadian timing may impair immune responses, promote inflammation, and compromise amyloid-β clearance. Therapeutic strategies targeting circadian regulation, including melatonin agonists and orexin receptor antagonists, may help mitigate cognitive decline. Additionally, the gut microbiome, modulated by circadian and sleep patterns, has emerged as a potential contributor to AD pathophysiology. This review also highlights interventions that support immune health, such as the Mediterranean diet, antiviral therapies, and physical activity, which may collectively attenuate AD risk. Finally, the bidirectional relationship between immune signaling and circadian rhythms, evidenced by immune modulation of clock genes, underscores a complex, integrated regulatory network. Understanding these interrelated systems may uncover novel approaches for prevention and treatment. By elucidating these interconnections, this review aims to shed light on novel therapeutic strategies and interventions that address multiple facets of the disease, offering potential avenues to improve outcomes for individuals with AD.

The arsenal of therapeutic options for HCC ranges from surgical strategies such as resection and Liver Transplantation (LT) to Locoregional Therapies (LRT), including ablation and transarterial procedures. Recently, the pool of resources available to treat HCC has been expanded with randomized clinical trials demonstrating the effectiveness of immune checkpoint inhibitors for the treatment of advanced HCC. Despite the wide variety of treatment options, tailoring the best strategy to each patient remains challenging. Several combinations of different treatments have been utilized in different clinical scenarios. In the setting of unresectable HCC, combining TACE with an ablation procedure such as Radiofrequency Ablation (RFA) or Microwave Ablation (MWA) is associated with improved outcomes over Transarterial Chemoembolization (TACE) alone. Additionally, TACE can be utilized as an adjuvant treatment for resected HCC with narrow margins. Patients waiting for LT may be treated with TACE combined with RFA or percutaneous ethanol injection to prevent tumor progression beyond the acceptable LT threshold. Immune checkpoint inhibitors given as adjuvant treatment following liver resection or TACE seem to improve recurrence-free survival. Finally, several trials are underway to investigate the role of immune checkpoint inhibitors as neoadjuvant therapy prior to liver resection. In conclusion, in many clinical settings, combining different approaches surpasses monotherapy for the treatment of HCC. Thus, the maxim "less is more" seems not to have stood the test of time.