Current drug targets最新文献

{"title":"Molecular Targets and Mechanisms of Hedyotis diffusa Willd. for Esophageal Adenocarcinoma Treatment Based on Network Pharmacology and Weighted Gene Co-expression Network Analysis.","authors":"Yu Zhuang, Yun-Gang Sun, Chen-Guang Wang, Qiang Zhang, Chao Che, Feng Shao","doi":"10.2174/0113894501265851240102101122","DOIUrl":"10.2174/0113894501265851240102101122","url":null,"abstract":"<p><strong>Background: </strong>Hedyotis diffusa Willd. (HDW) is a common anticancer herbal medicine in China, and its therapeutic effectiveness has been demonstrated in a range of cancer patients. There is no consensus about the therapeutic targets and molecular mechanisms of HDW, which contains many active ingredients.</p><p><strong>Aim: </strong>To clarify the mechanism of HDW for esophageal adenocarcinoma (EAC), we utilized network pharmacology and weighted gene co-expression network analysis methods (WGCNA).</p><p><strong>Methods: </strong>The gene modules that were linked with the clinical features of EAC were obtained through the WGCNA method. Then, the potential target genes were retrieved through the network pharmacology method in order to determine the targets of the active components. After enrichment analysis, a variety of signaling pathways with significant ratios of target genes were found, including regulation of trans-synaptic signaling, neuroactive ligand-receptor interaction and modulation of chemical synaptic transmission. By means of protein-protein interaction (PPI) network analysis, we have successfully identified the hub genes, which were AR, CNR1, GRIK1, MAPK10, MAPT, PGR and PIK3R1.</p><p><strong>Result: </strong>Our study employed molecular docking simulations to evaluate the binding affinity of the active components with the hub gene. The identified active anticancer constituents in HDW are scopoletol, quercetin, ferulic acid, coumarin, and trans-4-methoxycinnamyl alcohol.</p><p><strong>Conclusion: </strong>Our findings shed light on the molecular underpinnings of HDW in the treatment of EAC and hold great promise for the identification of potential HDW compounds and biomarkers for EAC therapy.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"431-443"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139424491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vaccine for Targeted Therapy of Lung Cancer: Advances and Developments.","authors":"Suraj Kumar, Rishabha Malviya, Prerna Uniyal","doi":"10.2174/0113894501306103240426131249","DOIUrl":"10.2174/0113894501306103240426131249","url":null,"abstract":"<p><p>Considering that lung cancer is a leading global perpetrator, novel treatment approaches must be investigated. Due to the broad spectrum of lung cancer, conventional therapies including chemotherapy, radiotherapy, and surgeries, are not always effective and can have adverse consequences. The present study's overarching objective was to enhance the development of a personalized vaccine for targeted lung cancer therapy. Vaccination functions by eliciting a strong and targeted immune response defense by taking advantage of the specific antigens that are expressed by lung cancer cells. Crucial antigens associated with tumor cells have been identified with the recognition of the genetic and immunological circumstances of lung cancer in this review. The vaccine includes these antigens to prime the immune system, directing it toward recognizing and attacking cancerous cells. In this review, we have addressed the possible benefits of a targeted vaccine strategy, which include a reduction in off-target effects and an improvement in health outcomes for patients. These studies highlight the promise of a tailored vaccine in a novel way for the treatment of lung cancer. The integration of molecular profiling and immunological insights offers a rationale for the design and implementation of personalized vaccines. While challenges exist, the promise of improved treatment outcomes and reduced side effects positions targeted vaccine therapy as a compelling avenue for advancing lung cancer treatment.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"526-529"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polymeric Micelle-Based Nanogels as Emerging Drug Delivery Systems in Breast Cancer Treatment: Promises and Challenges.","authors":"M Yazdan, S M Naghib, M R Mozafari","doi":"10.2174/0113894501294136240610061328","DOIUrl":"10.2174/0113894501294136240610061328","url":null,"abstract":"<p><p>Breast cancer is a pervasive global health issue that disproportionately impacts the female population. Over the past few years, there has been considerable interest in nanotechnology due to its potential utility in creating drug-delivery systems designed to combat this illness. The primary aim of these devices is to enhance the delivery of targeted medications, optimise the specific cells that receive the drugs, tackle treatment resistance in malignant cells, and introduce novel strategies for preventing and controlling diseases. This research aims to examine the methodologies utilised by various carrier nanoparticles in the context of therapeutic interventions for breast cancer. The main objective is to investigate the potential application of novel delivery technologies to attain timely and efficient diagnosis and treatment. Current cancer research predominantly examines diverse drug delivery methodologies for chemotherapeutic agents. These methodologies encompass the development of hydrogels, micelles, exosomes, and similar compounds. This research aims to analyse the attributes, intricacies, notable advancements, and practical applications of the system in clinical settings. Despite the demonstrated efficacy of these methodologies, an apparent discrepancy can be observed between the progress made in developing innovative therapeutic approaches and their widespread implementation in clinical settings. It is critical to establish a robust correlation between these two variables to enhance the effectiveness of medication delivery systems based on nanotechnology in the context of breast cancer treatment.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"649-669"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141449940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Effects of Melatonin in the Regulation of Ferroptosis: A Review of Current Evidence.","authors":"Mohammad Hossein Pourhanifeh, Azam Hosseinzadeh, Fereshteh Koosha, Russel J Reiter, Saeed Mehrzadi","doi":"10.2174/0113894501284110240426074746","DOIUrl":"10.2174/0113894501284110240426074746","url":null,"abstract":"<p><p>Ferroptosis is implicated in the pathogenesis of multiple diseases, including neurodegenerative diseases, cardiovascular diseases, kidney pathologies, ischemia-reperfusion injury, and cancer. The current review article highlights the involvement of ferroptosis in traumatic brain injury, acute kidney damage, ethanol-induced liver injury, and PM2.5-induced lung injury. Melatonin, a molecule produced by the pineal gland and many other organs, is well known for its anti- aging, anti-inflammatory, and anticancer properties and is used in the treatment of different diseases. Melatonin's ability to activate anti-ferroptosis pathways including sirtuin (SIRT)6/p- nuclear factor erythroid 2-related factor 2 (Nrf2), Nrf2/ antioxidant responsive element (ARE)/ heme oxygenase (HO-1)/SLC7A11/glutathione peroxidase (GPX4)/ prostaglandin-endoperoxide synthase 2 (PTGS2), extracellular signal-regulated kinase (ERK)/Nrf2, ferroportin (FPN), Hippo/ Yes-associated protein (YAP), Phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT)/ mammalian target of rapamycin (mTOR) and SIRT6/ nuclear receptor coactivator 4 (NCOA4)/ ferritin heavy chain 1 (FTH1) signaling pathways suggests that it could serve as a valuable therapeutic agent for preventing cell death associated with ferroptosis in various diseases. Further research is needed to fully understand the precise mechanisms by which melatonin regulates ferroptosis and its potential as a therapeutic target.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"543-557"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140853530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytokines and Regulating Epithelial Cell Division.","authors":"Basheer Abdullah Marzoog","doi":"10.2174/0113894501279979240101051345","DOIUrl":"10.2174/0113894501279979240101051345","url":null,"abstract":"<p><p>Physiologically, cytokines play an extremely important role in maintaining cellular and subcellular homeostasis, as they interact almost with every cell in the organism. Therefore, cytokines play a significantly critical role in the field of pathogenic pharmacological therapy of different types of pathologies. Cytokine is a large family containing many subfamilies and can be evaluated into groups according to their action on epithelial cell proliferation; stimulatory include transforming growth factor-α (TGF-α), Interlukine-22 (IL-22), IL-13, IL-6, IL-1RA and IL-17 and inhibitory include IL-1α, interferon type I (IFN type I), and TGF-β. The balance between stimulatory and inhibitory cytokines is essential for maintaining normal epithelial cell turnover and tissue homeostasis. Dysregulation of cytokine production can contribute to various pathological conditions, including inflammatory disorders, tissue damage, and cancer. Several cytokines have shown the ability to affect programmed cell death (apoptosis) and the capability to suppress non-purpose cell proliferation. Clinically, understanding the role of cytokines' role in epithelial tissue is crucial for evaluating a novel therapeutic target that can be of use as a new tactic in the management of carcinomas and tissue healing capacity. The review provides a comprehensive and up-to-date synthesis of current knowledge regarding the multifaceted effects of cytokines on epithelial cell proliferation, with a particular emphasis on the intestinal epithelium. Also, the paper will highlight the diverse signaling pathways activated by cytokines and their downstream consequences on epithelial cell division. It will also explore the potential therapeutic implications of targeting cytokine- epithelial cell interactions in the context of various diseases.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"190-200"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139424488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rho Kinase (ROCK) Inhibitors for the Treatment of Glaucoma.","authors":"Junhui Wu, Jing Wei, Haoliang Chen, Yalong Dang, Fang Lei","doi":"10.2174/0113894501286195231220094646","DOIUrl":"10.2174/0113894501286195231220094646","url":null,"abstract":"<p><p>Glaucoma is the most common cause of irreversible blindness worldwide. It is characterized by progressive optic nerve degeneration and loss of visual field. Pathological increased intraocular pressure is its main modifiable risk factor. Rho kinase inhibitors are developed as a new class of glaucoma medication that increases outflow facility from the conventional aqueous humor outflow pathway. Additionally, they also have neuroprotective and anti-scarring effects that can might increase the success rate of glaucoma filtration surgery. This review aims to summarize the current concept of Rho kinase inhibitors in the treatment of glaucoma from beach to bedside.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"94-107"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10964082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139058198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compounds Multi-targets against Neglected Diseases.","authors":"Luciana Scotti, Marcus T Scotti","doi":"10.2174/138945012509240724145557","DOIUrl":"10.2174/138945012509240724145557","url":null,"abstract":"","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":"25 9","pages":"575-576"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytovesicular Nanoconstructs for Advanced Delivery of Medicinal Metabolites: An In-Depth Review.","authors":"Vishal Pandey, Sunny Rathee, Debasis Sen, Sanjay K Jain, Umesh K Patil","doi":"10.2174/0113894501310832240815071618","DOIUrl":"10.2174/0113894501310832240815071618","url":null,"abstract":"<p><p>Phytochemicals, the bioactive compounds in plants, possess therapeutic benefits, such as antimicrobial, antioxidant, and pharmacological activities. However, their clinical use is often hindered by poor bioavailability and stability. Phytosome technology enhances the absorption and efficacy of these compounds by integrating vesicular systems like liposomes, niosomes, transfersomes, and ethosomes. Phytosomes offer diverse biological benefits, including cardiovascular protection through improved endothelial function and oxidative stress reduction. They enhance cognitive function and protect against neurodegenerative diseases in the nervous system, aid digestion and reduce inflammation in the gastrointestinal system, and provide hepatoprotective effects by enhancing liver detoxification and protection against toxins. In the genitourinary system, phytosomes improve renal function and exhibit anti-inflammatory properties. They also modulate the immune system by enhancing immune responses and reducing inflammation and oxidative stress. Additionally, phytosomes promote skin health by protecting against UV radiation and improving hydration and elasticity. Recent patented phytosome technologies have led to innovative formulations that improve the stability, bioavailability, and therapeutic efficacy of phytochemicals, although commercialization challenges like manufacturing scalability and regulatory hurdles remain. Secondary metabolites from natural products are classified into primary and secondary metabolites, with a significant focus on terpenoids, phenolic compounds, and nitrogen-containing compounds. These metabolites have notable biological activities: antimicrobial, antioxidant, antibiotic, antiviral, anti-inflammatory, and anticancer effects. In summary, this review amalgamates the latest advancements in phytosome technology and secondary metabolite research, presenting a holistic view of their potential to advance therapeutic interventions and contribute to the ever-evolving landscape of natural product-based medicine.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"847-865"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prostaglandins in the Inflamed Central Nervous System: Potential Therapeutic Targets.","authors":"Chynna-Loren Sheremeta, Sai Yarlagadda, Mark L Smythe, Peter G Noakes","doi":"10.2174/0113894501323980240815113851","DOIUrl":"10.2174/0113894501323980240815113851","url":null,"abstract":"<p><p>The global burden of neurological disorders is evident, yet there remains limited efficacious therapeutics for their treatment. There is a growing recognition of the role of inflammation in diseases of the central nervous system (CNS); among the numerous inflammatory mediators involved, prostaglandins play a crucial role. Prostaglandins are small lipid mediators derived from arachidonic acid via multi-enzymatic pathways. The actions of prostaglandins are varied, with each prostaglandin having a specific role in maintaining homeostasis. In the CNS, prostaglandins can have neuroprotective or neurotoxic properties depending on their specific G-protein receptor. These G-protein receptors have varying subfamilies, tissue distribution, and signal transduction cascades. Further studies into the impact of prostaglandins in CNS-based diseases may contribute to the clarification of their actions, hopefully leading to the development of efficacious therapeutic strategies. This review focuses on the roles played by prostaglandins in neural degeneration, with a focus on Alzheimer's Disease, Multiple Sclerosis, and Amyotrophic Lateral Sclerosis in both preclinical and clinical settings. We further discuss current prostaglandin-related agonists and antagonists concerning suggestions for their use as future therapeutics.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"885-908"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Promising New Targets for the Treatment of Infections Caused by <i>Acinetobacter baumannii</i>: A Review.","authors":"Kellen Christina Malheiros Borges, André Kipnis, Bruno Junior Neves, Ana Paula Junqueira-Kipnis","doi":"10.2174/0113894501319269240819060245","DOIUrl":"10.2174/0113894501319269240819060245","url":null,"abstract":"<p><p><i>Acinetobacter baumannii</i> is a globally disseminated Gram-negative bacterium that causes several types of serious nosocomial infections, the most worrisome being ventilator-associated pneumonia and bacteremia related to using venous catheters. Due to its great ability to form biofilms, combined with its survival for prolonged periods on abiotic surfaces and its potential to acquire and control the genes that determine antibiotic resistance, <i>A. baumannii</i> is at the top of the World Health Organization's priority list of pathogens in urgent need of new therapies. In this sense, this review aimed to present and discuss new molecular targets present in A. baumannii with potential for promising treatment approaches. This review highlights crucial molecular targets, including cell division proteins, membrane synthesis enzymes, and biofilm-associated components, offering promising targets for novel antimicrobial drug development against <i>A. baumannii</i> infections.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"971-986"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}