Current drug targets最新文献

{"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":"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}

{"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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774313/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does the Grape Products Intake has an Effect on Body Weight in Adults: A Systematic Review and Meta-analysis of Randomized Controlled Trials","authors":"Mohammad Ali Goudarzi, Zahra Sohrabi, Mohammad Hashem Hashempur, Saeed Nosratabadi, Zahra Namkhah, Cain C. T. Clark, Neda Haghighat","doi":"10.2174/0113894501272740231219072525","DOIUrl":"https://doi.org/10.2174/0113894501272740231219072525","url":null,"abstract":"Introduction:: There is a growing interest in the considerable benefits of grape products intake, as some studies have indicated that they may improve cardiometabolic risk factors. However, the widespread impact of grape products on the anthropometric indices is not fully resolved. Method:: The purpose of this systematic review and meta-analysis was to examine the effects of grape products intake on anthropometric indices in adults. Randomized controlled trials (RCT) examining the effects of grape products intake on anthropometric indices, published up to December 2021, were identified through PubMed, SCOPUS, and ISI Web of Science databases. 30 studies with 35 effect sizes, including 1284 participants (708 cases and 576 controls), were included and analyzed using a random-effects model to calculate weighted mean differences (WMDs) with 95% confidence interval (CI). Result:: The outcomes have revealed grape products intake to significantly decrease body weight (p = 0.001) and body mass index (p = 0.004) in obese participants, and also, a greater effect was observed when grape seed extract was used. Conclusion:: Our study suggests that grape products intake may help to decrease body weight in obese participants. Future large RCTs with longer duration and obese populations are needed to expand our findings.","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":"3 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2023-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139024043","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":"Transcription Factors in Brain Regeneration: A Potential Novel Therapeutic Target","authors":"Basheer Abdullah Marzoog","doi":"10.2174/0113894501279977231210170231","DOIUrl":"https://doi.org/10.2174/0113894501279977231210170231","url":null,"abstract":": Transcription factors play a crucial role in providing identity to each cell population. To maintain cell identity, it is essential to balance the expression of activator and inhibitor transcription factors. Cell plasticity and reprogramming offer great potential for future therapeutic applications, as they can regenerate damaged tissue. Specific niche factors can modify gene expression and differentiate or transdifferentiate the target cell to the required fate. Ongoing research is being carried out on the possibilities of transcription factors in regenerating neurons, with neural stem cells (NSCs) being considered the preferred cells for generating new neurons due to their epigenomic and transcriptome memory. NEUROD1/ASCL1, BRN2, MYTL1, and other transcription factors can induce direct reprogramming of somatic cells, such as fibroblasts, into neurons. However, the molecular biology of transcription factors in reprogramming and differentiation still needs to be fully understood.","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":"30 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138682836","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":"An Update on the Emerging Role of Wnt/β-catenin, SYK, PI3K/AKT, and GM-CSF Signaling Pathways in Rheumatoid Arthritis","authors":"Pradyuman Prajapati, Gaurav Doshi","doi":"10.2174/0113894501276093231206064243","DOIUrl":"https://doi.org/10.2174/0113894501276093231206064243","url":null,"abstract":": Rheumatoid arthritis is an untreatable autoimmune disorder. The disease is accompanied by joint impairment and anomalies, which negatively affect the patient’s quality of life and contribute to a decline in manpower. To diagnose and treat rheumatoid arthritis, it is crucial to understand the abnormal signaling pathways that contribute to the disease. This understanding will help develop new rheumatoid arthritis-related intervention targets. Over the last few decades, researchers have given more attention to rheumatoid arthritis. The current review seeks to provide a detailed summary of rheumatoid arthritis, highlighting the basic description of the disease, past occurrences, the study of epidemiology, risk elements, and the process of disease progression, as well as the key scientific development of the disease condition and multiple signaling pathways and enumerating the most current advancements in discovering new rheumatoid arthritis signaling pathways and rheumatoid arthritis inhibitors. This review emphasizes the anti-rheumatoid effects of these inhibitors [for the Wnt/β-catenin, Phosphoinositide 3-Kinases (PI3K/AKT), Spleen Tyrosine Kinase (SYK), and Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) signaling pathways], illustrating their mechanism of action through a literature search, current therapies, and novel drugs under pre-clinical and clinical trials.","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":"54 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138581866","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}