Current drug targets最新文献

{"title":"Statin Therapy and C-reactive Protein in Patients with Kidney Disease: A Systematic Review and Meta-analysis of Randomized Clinical Trials.","authors":"Bahman Razi, Danyal Imani, Saeed Aslani, Zeljko Reiner, Amirhossein Sahebkar","doi":"10.2174/0113894501302428240909150925","DOIUrl":"10.2174/0113894501302428240909150925","url":null,"abstract":"<p><strong>Background: </strong>Increased levels of inflammation markers in patients with kidney disease, particularly chronic kidney disease (CKD) is an important risk factor. This study explored whether the effect of more potent statins on inflammation in CKD patients is dose-dependent, whether there is any difference between the hydrophilic and lipophilic statins concerning their effects on inflammation markers in patients with CKD, and whether the duration of treatment with statins has any effect on markers of inflammation in these patients.</p><p><strong>Methods: </strong>A systematic literature search of Scopus, PubMed, and ISI Web of Science databases from inception to August 2022 was performed. Eligible studies were stratified based on a target population, intervention duration, dosage and type of statins (high intensity statin and moderate/ low intensity), and solubility of statins. Publication bias was evaluated using Begg's regression asymmetry test for visual inspection of funnel plots. Non-linear effects of dosage of statins and treatment duration were also examined by fractional polynomial modeling.</p><p><strong>Results: </strong>Meta-analysis of 10 RCTs (12 studies) on 264 patients with kidney disease and 254 controls showed a significant hs-CRP lowering effect of the dose of statin. Both hydrophilic and lipophilic statins had significant hs-CRP lowering effects. Meta-analysis of 6 publications (7 studies) evaluating the impact of statins on CRP in 235 patients and 197 control subjects showed a significant negative association between treatment with statins group and CRP levels.</p><p><strong>Conclusion: </strong>Statin treatment decreases significantly the levels of CRP and hs-CRP in patients with kidney disease.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"132-145"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343145","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":"Emerging Threats and Challenges of Monkeypox Virus: Exploration and Sensitivity.","authors":"Sejal Porwal, Rishabha Malviya, Sathvik Belagodu Sridhar, Manjeet Kaur","doi":"10.2174/0113894501355177241107062738","DOIUrl":"https://doi.org/10.2174/0113894501355177241107062738","url":null,"abstract":"","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926854","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":"Nrf2 and Ferroptosis: Exploring Translational Avenues for Therapeutic Approaches to Neurological Diseases.","authors":"Maneesh Mohan, Ashi Mannan, Chirag Kakkar, Thakur Gurjeet Singh","doi":"10.2174/0113894501320839240918110656","DOIUrl":"10.2174/0113894501320839240918110656","url":null,"abstract":"<p><p>Nrf2, a crucial protein involved in defense mechanisms, particularly oxidative stress, plays a significant role in neurological diseases (NDs) by reducing oxidative stress and inflammation. NDs, including Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, stroke, epilepsy, schizophrenia, depression, and autism, exhibit ferroptosis, iron-dependent regulated cell death resulting from lipid and iron-dependent reactive oxygen species (ROS) accumulation. Nrf2 has been shown to play a critical role in regulating ferroptosis in NDs. Age-related decline in Nrf2 expression and its target genes (HO-1, Nqo-1, and Trx) coincides with increased iron-mediated cell death, leading to ND onset. The modulation of iron-dependent cell death and ferroptosis by Nrf2 through various cellular and molecular mechanisms offers a potential therapeutic pathway for understanding the pathological processes underlying these NDs. This review emphasizes the mechanistic role of Nrf2 and ferroptosis in multiple NDs, providing valuable insights for future research and therapeutic approaches.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"33-58"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343144","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":"Advances in Cysteine Protease B Inhibitors for Leishmaniasis Treatment.","authors":"Ana Luisa Rodriguez Gini, Emilio Emilio João, Juliana Romano Lopes, Pamela Souza Tada Da Cunha, Angela Maria Arenas Velasquez, Marcia Aparecida Silva Graminha, Jean Leandro Dos Santos, Caue Benito Scarim","doi":"10.2174/0113894501324437240919064715","DOIUrl":"10.2174/0113894501324437240919064715","url":null,"abstract":"<p><p>The expression and release of cysteine proteases by <i>Leishmania</i> spp. and their virulence factors significantly influence the modulation of host immune responses and metabolism, rendering cysteine proteases intriguing targets for drug development. This review article explores the substantial role of cysteine protease B (CPB) in medicinal chemistry from 2001 to 2024, particularly concerning combatting <i>Leishmania</i> parasites. We delve into contemporary advancements and potential prospects associated with targeting cysteine proteases for therapeutic interventions against leishmaniasis, emphasizing drug discovery in this context. Computational analysis using the pkCSM tool assessed the physicochemical properties of compounds, providing valuable insights into their molecular characteristics and drug-like potential, enriching our understanding of the pharmacological profiles, and aiding rational inhibitor design. Our investigation highlights that while nonpeptidic compounds constitute the majority (69.2%, 36 compounds) of the dataset, peptidomimetic- based derivatives (30.8%, 16 compounds) also hold promise in medicinal chemistry. Evaluating the most promising compounds based on dissociation constant (<i>Ki</i>) and half maximal inhibitory concentration (IC₅₀) values revealed notable potency, with 41.7% and 80.0% of nonpeptidic compounds exhibiting values < 1 μM, respectively. On the other hand, all peptidic compounds evaluated for <i>Ki</i> (43.8%) and IC₅₀ (31.3%) obtained values < 1 μM, respectively. Further analysis identified specific compounds within both categories (nonpeptidic: 1, 2, and 4; peptidic: 48-52) as particularly promising, warranting deeper investigation into their structure-activity relationships. These findings underscore the diverse landscape of inhibitors in medicinal chemistry and highlight the potential of both nonpeptidic and peptide-based compounds as valuable assets in therapeutic development against leishmaniasis.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"88-108"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343140","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":"Emerging Role of NAT10 as ac4C Writer in Inflammatory Diseases: Mechanisms and Therapeutic Applications.","authors":"Wencheng Zhang, Weiping Lu, Min Wang, Di Yao, Jun Ma, Xiaoyan Hu, Mengyuan Tao","doi":"10.2174/0113894501346709241202110834","DOIUrl":"https://doi.org/10.2174/0113894501346709241202110834","url":null,"abstract":"<p><p>The incidence of inflammatory diseases, including infections, autoimmune disorders, and tumors, is consistently increasing year by year, posing a significant and growing threat to human health on a global scale. Recent research has indicated that RNA acetylation modification, a specific type of post-transcriptional modification, may play a critical role in the pathogenesis of these diseases. Among the various mechanisms of RNA modification, N-acetyltransferase 10 (NAT10) has been identified as the sole cytidine acetyltransferase in eukaryotes. NAT10 is responsible for acetylating mRNA cytosine, which leads to the formation of N4-acetylcytidine (ac4C), a modification that subsequently influences mRNA stability and translation efficiency. Despite these insights, the specific roles and underlying mechanisms by which RNA acetylation contributes to the onset and progression of inflammatory diseases remain largely unclear. This review aimed to elucidate the alterations in NAT10 expression, the modifications it induces in target genes, and its overall contribution to the pathogenesis of various inflammatory conditions. It has been observed that NAT10 expression tends to increase in most inflammatory conditions, thereby affecting the expression and function of target genes through the formation of ac4C. Furthermore, inhibitors targeting NAT10 present promising therapeutic avenues for treating inflammatory diseases by selectively blocking NAT10 activity, thereby preventing the modification of target genes and suppressing immune cell activation and inflammatory responses. This potential for therapeutic intervention underscores the critical importance of further research on NAT10's role in inflammatory disease pathogenesis, as understanding these mechanisms could lead to significant advancements in treatment strategies, potentially transforming the therapeutic landscape for these conditions.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779633","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":"Unraveling Neurological Drug Delivery: Polymeric Nanocarriers for Enhanced Blood-Brain Barrier Penetration.","authors":"Aparna Inamdar, Bannimath Gurupadayya, Praveen Halagali, Vamshi Krishna Tippavajhala, Farhan Khan, Rashmi Pathak, Himanshu Sharma","doi":"10.2174/0113894501339455241101065040","DOIUrl":"https://doi.org/10.2174/0113894501339455241101065040","url":null,"abstract":"<p><p>Treating neurological illnesses is challenging because the blood-brain barrier hinders therapeutic medications from reaching the brain. Recent advances in polymeric nanocarriers (PNCs), which improve medication permeability across the blood-brain barrier, may influence therapy strategies for neurological diseases. PNCs have several ways to deliver medications to the nervous system. This review article provides a summary of the parts and manufacturing methods involved in making PNCs. Additionally, it highlights the elements that result in PNCs having enhanced blood-brain barrier penetration. A combination of passive and active targeting strategies is used by PNCs intended to overcome the blood-brain barrier. Among these are micellar structures, nanogels, nanoparticles, cubosomes, and dendrimers. These nanocarriers, which are functionalized with certain ligands that target BBB transporters, enable the direct delivery of drugs to the brain. Mainly, the BBB prevents medications from entering the brain. Understanding the BBB's physiological and anatomical characteristics is necessary to get over this obstacle. Preclinical and clinical research demonstrates the safety and effectiveness of these PNCs, and their potential use in the treatment of neurological illnesses, including brain tumors, Parkinson's disease, and Alzheimer's disease, is discussed. Concerns that PNCs may have about their biocompatibility and possible toxicity are also covered in this review article. This study examines the revolutionary potential of PNCs in CNS drug delivery, potential roadblocks, ongoing research, and future opportunities for PNC design progress. PNCs open the door to more focused and efficient treatment for neurological illnesses by comprehending the subtleties of BBB penetration.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603556","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":"LncRNA HAGLROS: A Vital Oncogenic Propellant in Various Human Cancers.","authors":"Jingjie Yang, Haodong He, Lihan Chen, Yuzhang Wei, Yulong Liu, Xiaolan Li, Chengfu Yuan","doi":"10.2174/0113894501345632241022055444","DOIUrl":"https://doi.org/10.2174/0113894501345632241022055444","url":null,"abstract":"<p><p>HAGLR Opposite Strand lncRNA (HAGLROS) is a long non-coding RNA (lncRNA) located on the long arm of human chromosome 2 at locus 2q31.1. Emerging evidence highlights HAGLROS as a pivotal player in human cancers, characterized by its significant upregulation across multiple malignancies where it functions as an oncogenic driver. Its aberrant expression is closely linked to the initiation and progression of 13 distinct cancer types, notably correlating with adverse clinical outcomes and reduced overall survival rates in 9 of these cancer types. Mechanistically, HAGLROS is under the regulatory influence of the transcription factor STAT3, exerts competitive binding to 9 miRNAs, activates 5 signaling pathways pivotal for cancer cell proliferation and metastasis, as well as intricately modulates gene expression profiles. Given its multifaceted roles, HAGLROS emerges as a promising candidate for cancer diagnostics and prognostics. Moreover, its potential as a therapeutic target holds considerable promise for novel treatment strategies in oncology. This review synthesizes current research on HAGLROS, covering its expression patterns, biological roles, and clinical significance in cancer. By shedding light on these aspects, this review aims to contribute new perspectives that advance our understanding of cancer biology, enhance diagnostic accuracy, refine prognostic assessments, and pave the way for targeted therapeutic interventions.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557348","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":"Trends of Artificial Intelligence (AI) Use in Drug Targets, Discovery and Development: Current Status and Future Perspectives.","authors":"Manmayee Mohapatra, Chittaranjan Sahu, Snehamayee Mohapatra","doi":"10.2174/0113894501322734241008163304","DOIUrl":"https://doi.org/10.2174/0113894501322734241008163304","url":null,"abstract":"<p><p>The applications of artificial intelligence (AI) in pharmaceutical sectors have advanced drug discovery and development methods. AI has been applied in virtual drug design, molecule synthesis, advanced research, various screening methods, and decision-making processes. In the fourth industrial revolution, when medical discoveries are happening swiftly, AI technology is essential to reduce the costs, effort, and time in the pharmaceutical industry. Further, it will aid \"genome-based medicine\" and \"drug discovery.\" AI may prepare proactive databases according to diseases, disorders, and appropriate usage of drugs which will facilitate the required data for the process of drug development. The application of AI has improved clinical trials on patient selection in a population, stratification, and sample assessment such as biomarkers, effectiveness measures, dosage selection, and trial length. Various studies suggest AI could be perform better compared to conventional techniques in drug discovery. The present review focused on the positive impact of AI in drug discovery and development processes in the pharmaceutical industry and beneficial usage in health sectors as well.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544237","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":"Current Updates on Pathogenesis, Systemic Therapy, and Treatment of Invasive Fungal Infections.","authors":"Sushil Kumar Singh, Shyam Sundar Pancholi","doi":"10.2174/0113894501337502241015121015","DOIUrl":"https://doi.org/10.2174/0113894501337502241015121015","url":null,"abstract":"<p><p>Numerous health hazards are associated with fungal infections, ranging from asymptomatic cases to potentially fatal invasive diseases that are especially dangerous for those with impaired immune systems. The main causes behind these diseases are opportunistic fungi, namely Aspergillus, Candida, and Cryptococcus. Invasive fungal infections (IFIs) require a global response that includes the development of vaccines, standardized protocols for diagnosis, potent antifungal medications, and strategies to stop drug-resistant strains. Improving high-risk group diagnosis and treatment is essential to lowering death rates. This review highlights the substantial health concerns associated with fungal infections, especially in immunocompromised individuals, and identifies Aspergillus, Candida, and Cryptococcus as the main pathogens. It highlights the necessity of international efforts, such as the development of novel diagnostic instruments, imaging methods, and antifungal drugs, to combat these invasive infections. The review also addresses the increasing need for novel treatment approaches in light of the developing resistance to widely used antifungal medications. Furthermore, the significance of secretory proteins in fungal pathogenicity and the potential of combination therapy are investigated. It is also suggested that a multimodal strategy be used to fight these illnesses, given the promise of multivalent vaccinations. Overall, this study emphasizes how critical it is to develop better diagnostic and treatment strategies in order to successfully control and lessen the impact of invasive fungal diseases on the health of the world.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459972","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":"Molecular Insight into Obesity-Associated Nephropathy: Clinical Implications and Possible Strategies for its Management.","authors":"Himani Gupta, Uma Bhandari","doi":"10.2174/0113894501314788241008115712","DOIUrl":"https://doi.org/10.2174/0113894501314788241008115712","url":null,"abstract":"<p><p>Obesity is a significant health concern due to its rapid increase worldwide. It has been linked to the pathogenic factors of renal diseases, cancer, cardiovascular diseases, hypertension, dyslipidemia, and type 2 diabetes. Notably, obesity raises the likelihood of developing chronic kidney disease (CKD), leading to higher adult mortality and morbidity rates. This study explores the molecular mechanisms that underlie obesity-associated nephropathy and its clinical implications. Obesity-Associated Nephropathy (OAN) develops and worsens due to insulin resistance and hyperinsulinemia, which promote renal sodium reabsorption, glomerular hyperfiltration, and hypertension, leading to progressive kidney damage. Renal damage is further aggravated by persistent inflammation and redox damage, mediated by adipokines and proinflammatory cytokines, such as TNF-α and IL-6. Furthermore, stimulation of the sympathetic nervous system and the renin-angiotensin- aldosterone system (RAAS) intensifies glomerular hypertension and fibrosis. These elements cause glomerular hyperfiltration, renal hypertrophy, and progressive kidney damage. Clinical manifestations of obesity-associated nephropathy include proteinuria, reduced glomerular filtration rate (GFR), and ultimately, CKD. Management strategies currently focus on lifestyle modifications, such as weight loss through diet and exercise, which have been effective in reducing proteinuria and improving GFR. Pharmacological treatments targeting metabolic pathways, including GLP-1 receptor agonists and SGLT2 inhibitors, have shown renoprotective properties. Additionally, traditional RAAS inhibitors offer therapeutic benefits. Early detection and comprehensive management of OAN are essential to prevent its progression and lessen the burden of CKD.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459973","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}