Current pharmaceutical design最新文献

Introduction: Nitrergic transmission and oxidative stress are complicated factors in the seizure's pathophysiology. Syringic acid has been revealed to exert numerous pharmacological properties, including neuroprotective effects. Hence, this research was designed to explore the anticonvulsant effects of syringic acid, focusing on its possible impact on nitrergic transmission and oxidative stress in the prefrontal cortex (PFC) in mice that underwent induction of seizure using pentylenetetrazole (PTZ).

Methods: Forty male NMRI mice were randomly divided into five groups, including mice that received saline containing Tween 80 at a concentration of 1% (10 ml/kg), syringic acid at doses of 10, 20, and 30 mg/kg, and diazepam (10 mg/kg). Syringic acid was dissolved in saline containing Tween 80 at a concentration of 1%. All drugs were injected intraperitoneally one hour before seizure induction by PTZ. Seizure threshold, total antioxidant capacity (TAC), nitrite, and malondialdehyde (MDA) levels, as well as inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS) gene expressions, were assessed in the PFC.

Results: Syringic acid increased the seizure threshold and TAC, whereas it decreased MDA and nitrite levels in the PFC samples. Furthermore, syringic acid diminished the expression of iNOS and nNOS genes in the PFC.

Discussion: Oxidative/nitrosative stress, which is involved in the pathophysiology of seizure, was alleviated by syringic acid.

Conclusion: It was concluded that, at least partially, the anticonvulsant property of syringic acid was mediated through the mitigation of oxidative stress and nitrergic transmission in the PFC in PTZ-induced seizures in male mice.

Introduction: Qiangjie Xinyi Decoction (QJXYD) has been effectively utilized in the clinical treatment of Northwest Dryness Syndrome (NDS) with allergic rhinitis (AR). However, its therapeutic effect lacks a theoretical basis. This study employs network pharmacology and experimental validation to investigate the therapeutic potential of QJXYD on NDS with AR and elucidate its mechanism of action.

Methods: Databases such as TCMSP, OMIM, Genecards, etc. were used to obtain relevant targets for traditional Chinese medicine and diseases. A protein interaction network (PPI) was constructed in the STRING database to screen the core targets of QJXYD for the prevention and treatment of AR. A drug-diseasepathway network diagram was constructed using Cytoscape 3.9.0 to identify the main active ingredients that exert efficacy. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed using the DAVID database. The significant findings were subsequently validated through molecular dynamics simulations. An NDS was established with the AR model in rats, and the network pharmacology results were validated through in vivo experiments.

Results: The key targets screened for PPI network construction included IL-6, TNF, VEGFA, etc. Key components such as quercetin, luteolin, and beta-sitosterol were explored in the component target pathway network diagram. GO functional enrichment mainly involved protein binding, inflammatory response, and other functions. KEGG enrichment analysis included pathways such as Th17 cell differentiation and the HIF-1 signaling pathway. Molecular docking and molecular dynamics simulations validated the research results. Animal experiments showed that QJXYD can reduce the protein and gene expression of IL-6, TNF, and VEGFA in the nasal mucosal tissue of NDS with AR rats.

Discussion: This study, utilizing network pharmacology and animal experiments, found that QJXYD may target IL-6, TNF, and other targets through components such as quercetin, thereby regulating inflammation-related pathways to treat AR. Animal experiments confirmed that it can reduce the expression of key targets in the nasal mucosa. The research system revealed the mechanism of the compound, but there are limitations, such as unverified predictions and insufficient clinical representativeness of the model, which require further research.

Conclusion: QJXYD can treat NDS with AR through multiple components, targets, and pathways, providing a theoretical basis for further research.

Introduction: Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths globally. Traditional treatments face limitations like low effectiveness, poor specificity, and significant side effects. Gene therapy, particularly siRNA-based, is promising for targeted gene regulation but requires effective delivery systems due to the instability and poor target delivery of unmodified siRNA.

Methods: This study examined the storage and biological stability of LP-PEI-SPION (LPS) and GPC3-LPPEI- SPION (GLPS). The potential of these agents as tumor imaging contrast agents and the targeting ability of gene delivery carriers were assessed through ex vivo organ fluorescence imaging and in vivo tumor magnetic resonance imaging (MRI). Antitumor efficacy was evaluated through tumor volume, protein blotting, immunohistochemistry, and TUNEL assays. In vivo safety was evaluated using HE staining, nude mouse weight changes, and blood biochemical indicators.

Results: LPS and GLPS both formed stable siRNA complexes. GLPS showed excellent tumor targeting in vivo. MRI results showed that the GPC3-targeting peptide effectively enhanced the MR imaging performance and diagnostic accuracy. Tumor volume and weight measurements demonstrated potent tumor inhibition by GLPS/siRNA. Immunoblotting and immunohistochemistry revealed significant GPC3 reduction in the GLPS/ siRNA-targeted group. Safety evaluations confirmed good biocompatibility for both LPS/siRNA and GLPS/ siRNA.

Conclusion: GLPS/siRNA demonstrates good stability, tumor targeting, imaging capability, and antitumor efficacy with favorable safety, positioning it as a promising theragnostic platform for HCC. This integrated system provides novel clinical tools for diagnosis and treatment, establishes a foundation for clinical translation, and enables simultaneous tumor imaging and gene therapy-offering innovative strategies for combined tumor theranostics.

Many people worldwide suffer from various ear diseases, and their treatments are still challenging. The tympanic, round, and oval windows, and the blood-perilymph barrier are the three main physical obstacles to drug delivery. Conventional methods, such as oral administration or injections, often fail to overcome these obstacles. However, local drug delivery systems present a potential solution by reducing side effects and allowing higher drug concentrations to reach the inner ear. Numerous drug delivery techniques and patents have been evaluated in clinical and research settings in recent years. Even though otic drug delivery has evolved, there are still a number of issues, and further study is required to maximize these therapeutic modalities for clinical use. This review summarizes various local drug delivery techniques. Current barriers in otic drug delivery are highlighted, as well as innovative systems for future clinical applications.

Introduction: The purpose of this research is to review and evaluate both traditional and emerging biomarkers used in the diagnosis, monitoring, and treatment of liver diseases. The study aims to highlight how these biomarkers-such as liver enzymes, microRNAs, exosomes, and fibrosis-related proteins-can improve early detection, track disease progression, and support personalized treatment strategies for better patient outcomes.

Methods and material: This study uses a literature review to analyze both traditional (ALT, AST, ALP, bilirubin, etc.) and emerging biomarkers (microRNAs, exosomes, CRP, IL-6, MMPs, TIMPs) in liver disease. It focuses on their role in diagnosis, disease monitoring, and personalized treatment planning.

Results: Traditional biomarkers (ALT, AST, ALP, bilirubin, albumin) are key for liver function assessment. Emerging markers like microRNAs, exosomes, MMPs, and TIMPs improve early detection and disease monitoring. Together, they enhance diagnostic accuracy and support personalized treatment.

Discussion: The combination of traditional and novel biomarkers improves early detection, accurate diagnosis, and personalized treatment of liver diseases. New biomarkers, such as microRNAs and exosomes, offer higher sensitivity and specificity, enabling non-invasive diagnostics. The findings align with current research trends that promote the use of molecular and extracellular markers. These biomarkers provide deeper insights into liver disease mechanisms, particularly in fibrosis and hepatocellular carcinoma.

Conclusion: Traditional biomarkers are essential for liver assessment, while new ones like microRNAs, exosomes, MMPs, and TIMPs improve early diagnosis and monitoring. They support personalized care but need further validation for routine use.

Background: Triple-negative breast cancer (TNBC) is characterized by the absence of HER2 expression, progesterone receptor (PR), and estrogen receptor (ER). TNBC has a poor prognosis and limited therapy options due to its lack of specific targets and aggressive behavior.

Aim: This review demonstrates the therapeutic efficacy and mechanisms of natural compounds in targeting key molecular pathways involved in the development and progression of TNBC, investigating their interaction with oncogenic signaling pathways.

Methods: A thorough literature review was conducted using databases such as PubMed, Scopus, and Web of Science to identify studies assessing the anti-TNBC properties of natural compounds.

Results: Natural bioactive compounds like curcumin, resveratrol, quercetin, EGCG, berberine, and thymoquinone have demonstrated promising anticancer properties in TNBC models. These limit metastasis, induce apoptosis, inhibit proliferation, and reverse chemoresistance by altering vital pathways like PI3K/AKT/ mTOR, MAPK/ERK, NF-κB, JAK/STAT, and Wnt/β-catenin. For example, quercetin inhibits NF-κB signalling and increases the cytotoxicity of doxorubicin, but curcumin decreases AKT phosphorylation. Furthermore, natural compounds may enhance immune response in BRCA-mutated TNBC by modifying immunological checkpoints, including PD-L1, when combined with PARP inhibitors.

Conclusion: Natural compounds are a promising supplementary method for TNBC therapy due to their ability to target unregulated pathways and overcome therapeutic resistance. Nevertheless, challenges such as pharmacokinetics, limited bioavailability, and a lack of clinical validation persist. Future research should focus on combinatorial regimens, nanocarrier-based delivery technologies, and biomarker-guided clinical trials to develop successful TNBC treatments.

Cytokine Release Syndrome (CRS) is a hyperinflammatory condition triggered by infections, immunotherapies, and systemic immune dysregulation. PANoptosis, a unique form of programmed inflammatory cell death that integrates pyroptosis, apoptosis, and necroptosis, has emerged as a key contributor to CRS pathogenesis. This review explores the mechanistic role of PANoptosis in CRS, with particular emphasis on immunotherapy-induced toxicity and viral infections such as SARS-CoV-2 and influenza. PANoptosis exacerbates cytokine storms through ZBP1, NLRP3, and CASP8-mediated pathways, creating a pathological feedback loop that intensifies inflammation and promotes multi-organ damage. Current evidence suggests that modulating PANoptotic pathways, including targeting TNF-α, IFN-γ, and inflammasome components, may mitigate cytokine-driven tissue injury. Despite growing interest, the therapeutic potential of PANoptosis remains underexplored. Advancing our understanding of PANoptosis and its interaction with cytokine signaling will be critical for developing effective interventions for CRS and improving outcomes in patients undergoing immunotherapy or battling severe infections.

Objectives: The delivery of healthcare services via information and communication technology, or telemedicine, has grown to be an essential part of modern medicine. This study explores the evolving role of telemedicine, focusing on its expansion into the Metaverse, and evaluates its potential to improve healthcare accessibility, patient engagement, and medical outcomes.

Methods: A comprehensive analysis of the literature was conducted, evaluating studies investigating the efficacy of telemedicine in different medical fields, notably mental health, chronic disease management, and postsurgical follow-ups. This study assessed the impact of emerging technologies, specifically virtual reality (VR) and augmented reality (AR), on telemedicine, emphasizing their applications within the Metaverse. Furthermore, ethical considerations, insurance limitations, and technological disparities were assessed.

Results: Telemedicine has significantly enhanced healthcare access, especially in remote and underserved regions. Patient satisfaction and purpose to continue with telemedicine services are elevated, particularly in specialized areas like Tele-stroke and mental health counseling.

Discussion: The Metaverse has the potential to transform telemedicine through the establishment of immersive and interactive healthcare settings. VR and AR have the potential to facilitate virtual consultations, enhancing the interaction between patients and healthcare professionals. Additionally, the integration of data may lead to improvements in diagnostic accuracy and treatment planning. However, issues such as data privacy, cybersecurity hazards, and the digital gap must be addressed to provide adequate access.

Conclusion: Telemedicine has demonstrated significant utility within modern healthcare, and its incorporation with the Metaverse offers novel prospects for improving patient care, advancing medical education, and facilitating collaborative research. Despite the promising benefits, it is crucial to address technological, ethical, and regulatory challenges to ensure widespread adoption and successful implementation.

Introduction: Disorders of mood and post-traumatic stress disorder (PTSD) are common after major trauma, and one of the treatments used is Tricyclic Antidepressants (TCA). These medications work by inhibiting the re-uptake of neurotransmitters like serotonin and noradrenaline. Serotonin is known to have measurable effects on bone tissue due to the presence of specific receptors on bone cells. However, there are conflicting reports about how serotonin signaling affects bone tissue and the process of fracture healing. This study aimed to evaluate the effect of TCAs on fracture healing.

Method: Twelve skeletally mature Wistar rats were used in the study. All rats underwent intra-medullary pinning of the right tibia, and a complete mid-diaphyseal fracture was created. The rats were then randomly split into two groups: a control group and a study group. For twenty-eight days, the study group received a daily dose of 10 mg/kg of amitriptyline via intraperitoneal infusion, while the control group received an equal volume of plain saline via the same route. On day twenty-eight, five hours after the final dose, all rats were euthanized to assess fracture healing using radiological, microscopic, and histological methods.

Results: The study found a significant difference in the total volume of new bone formation between the two groups on day twenty-eight. The control group had a mean bone formation volume of 1.077 mm³, whereas the amitriptyline-treated group had a significantly higher mean volume of 1.824 mm³ (p<0.01).

Discussion: The results suggest that TCAs positively influence the early phases of fracture healing. The increased new bone formation observed in the amitriptyline group indicates a potential therapeutic benefit beyond their known psychiatric effects. This finding adds to the existing literature on the complex relationship between serotonin signaling and bone metabolism, providing evidence that this class of antidepressants may enhance the process of bone repair.

Conclusion: Tricyclic Antidepressants, specifically amitriptyline, significantly increase new bone formation in the early stages of fracture healing in Wistar rats.

Cataract remains one of the leading causes of blindness worldwide. Studies have shown that its onset is predominantly age-related, particularly affecting the elderly. According to the latest report by the World Health Organization (WHO), more than fifty percent of global blindness cases are attributed to cataracts alone. If timely and appropriate measures are not implemented, this percentage is projected to double in the coming decades. Therefore, there is an urgent need to develop alternative approaches to manage cataracts more effectively, beyond the current reliance on surgical intervention. In recent years, researchers have been actively exploring simpler, non-surgical treatment options that could potentially dissolve cataracts in their early stages. The successful development of such therapies would mark a significant breakthrough and offer immense benefits to humanity. This article highlights the evolution of surgical techniques used in cataract management, from traditional practices to modern innovations, while also discussing emerging non-invasive strategies such as lanosterol-based pharmacotherapy, nanomedicine-driven drug delivery systems, and regenerative approaches like stem cell therapy. These advances signal a promising future for safer, more accessible, and more effective cataract care.