Current pharmaceutical design最新文献

In recent years, green tea (Camellia sinensis) has garnered significant attention for its potential health benefits, including its benefits for oral hygiene. Green tea contains several bioactive components, including catechins, polyphenols, and fluoride, which contribute to its antibacterial, anti-inflammatory, and antioxidant properties. This review examines the bioactive components of green tea, specifically catechins, polyphenols, and fluoride, which possess numerous biological effects, including oral health benefits. As a result of its ability to neutralize volatile sulfur compounds, green tea inhibits the growth of cariogenic bacteria, such as Streptococcus mutans, reduces plaque development, and inhibits the development of halitosis. Recent evidence suggests that epigallocatechin-3-gallate (EGCG) has significant potential for oral health benefits. Furthermore, its anti-inflammatory effects help reduce gingival inflammation and oxidative stress, thereby easing the symptoms of periodontal disease. Numerous studies have shown that EGCG inhibits the growth of oral squamous cell carcinoma through mechanisms that include the induction of oxidative stress and apoptosis in cancer cells, as well as the inhibition of tumor invasion. This review discusses the potential mechanisms by which green tea promotes oral health and its therapeutic applications in dentistry. The literature review suggests that green tea may have potential as an adjunctive therapy for preventing and managing dental complications. However, more comprehensive pre-clinical and clinical studies are necessary to validate its efficacy. Furthermore, factors such as individual variability, patients' oral health conditions, long-term outcomes, and alterations in the oral microbiome require thorough investigation.

Introduction: Millions of people have died from zoonotic illnesses, like COVID-19 and Nipah virus infection (NiV), throughout history. Fruit bats (Pteropus sp.) are the main reservoir host for NiV, an RNA virus belonging to the Henipavirus group, which causes extremely infectious illnesses, such as COVID- 19. NiV outbreaks have posed significant public health concerns, especially in South and Southeast Asia. The Nipah virus (NiV) infection is caused by a virus that belongs to the Paramyxoviridae family's Henipavirus genus. It is the source of zoonosis, which causes respiratory and neurological symptoms.

Methods: This study has reviewed the epidemiology, pathophysiology, genetic diversity, and phylogenetics of NiV. It has explored NiV's clinical features, cellular monitoring, infection factors, and the virus' reservoir host.

Results: Phylogenetic analysis has identified two circulating NiV lineages. Additionally, the study has examined the role of phytochemicals in combating viral infections. Despite the absence of a focused therapy for COVID-19, phytochemicals have been investigated for their potential antiviral properties. Evidence suggests that plants and their components may possess resistance against NiV by modulating the immune system and inhibiting viral replication.

Discussion: The investigation into plant-derived compounds has offered a novel direction for NiV treatment, potentially enhancing viral resistance through immune modulation. Continued research on natural antivirals could bridge current gaps in therapeutic options for emerging zoonotic diseases.

Conclusion: The study has highlighted the transmission risk, detection challenges, and the potential of phytochemicals in managing NiV infections. The therapeutic potential of plants and their antiviral properties offer promising insights into future treatments for serious viral diseases, like NiV.

A complicated anatomy comprising genetic, environmental, and lifestyle variables, cancer continues to be one of the top causes of death globally. Thanks to developments in molecular biology, the genetic mutations and epigenetic changes responsible for the onset and spread of cancer have been identified. Although our understanding of cancer biology has advanced significantly, therapy problems arise from the disease's heterogeneity. Surgery, chemotherapy, radiation, and targeted medicines are examples of modern therapeutic approaches that have increased survival rates but frequently have serious side effects and resistance problems. The complicated pathophysiology and essential location of brain cancer provide substantial hurdles. It encompasses both primary brain tumors and metastatic lesions. Gliomas, meningiomas, and medulloblastomas are examples of primary brain tumors that originate from distinct cell types within the brain, which differ in their aggressiveness and responsiveness to treatment. The most prevalent and aggressive type, known as glioblastoma multiforme (GBM), grows rapidly and is resistant to standard therapies. The diagnosis of brain cancer is now more accurate thanks to developments in neuroimaging and molecular diagnostics, which also allow for more precise tumor subtype identification and individualized treatment plans. Conventional therapies consist of radiation therapy, chemotherapy, and surgical resection; newer techniques, including immunotherapy and targeted therapies, are frequently added. In this review article, the pathophysiology of brain cancer, its diagnosis, and treatments using novel technology will be discussed. Moreover, it highlights FDAapproved drugs used in treating brain cancer, along with previous, ongoing, and future aspects in which modifications are made to enhance the efficacy of these drugs. This has been made possible due to advancements in nano-formulation techniques, which have enabled the development of novel drug delivery systems.

Introduction: This research aimed to reveal the role of antioxidants and DNMT1 gene expression in behavioral disorders after exposure to stress.

Methods: Forty-eight male and female mice (weight 25-35 grams) were used. Their pups (weight 18-22 grams) were divided into 6 groups (n=20), Control, Social isolation stress (SIS), and SIS + N-acetylcysteine (NAC) 150 mg/kg intraperitoneally for male and 3 similar groups for female subjects, eight mice from each group were used for the first-generation experiments and another for mating and producing the second generation. The second-generation pups were designated into 9 groups A to I. After conducting behavioral tests of the Morris water maze (MWM) and shuttle box, they were anesthetized, decapitated, and their brains were removed. The neuronal counts of CA1 and CA3 were performed. DNMT1 gene expression, total antioxidant capacity (TAC), and malondialdehyde (MDA) of the brain were measured.

Results: Spatial memory, passive avoidance, and TAC decreased in the SIS groups. MDA and DNMT1 gene expression of the SIS groups increased (p<0.001). Dead neurons in the CA1 and CA3 regions increased in the SIS group (p<0.001).

Discussion: According to the results of this study, N-acetylcysteine enhanced learning and memory while reducing neuronal death by decreasing oxidative stress. Additionally, it lowered the expression of the DNMT1 gene, which plays a crucial role in DNA methylation.

Conclusion: After studying the human population, N-acetylcysteine may be introduced as an adjunct therapy to help mitigate the effects of stress.

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.