Pub Date : 2025-01-15DOI: 10.2174/0113816128348877241202053633
Saif Ahmad Khan, Zufika Qamar, Aashish Rohilla, Pirthi Pal Singh, Suhel Parvez, Sanjula Baboota, Javed Ali
Alzheimer's disease (AD) is a debilitating condition that significantly affects the elderly. Early diagnosis is not only critical for improving patient outcomes but also directly influences the success of emerging therapeutic interventions. A therapeutic strategy targeting only one pathogenic mechanism is unlikely to be very effective, as there is increasing evidence that AD does not have a single pathogenic cause. Therefore, combining medications or developing therapies that address multiple pathways may be beneficial. Most clinical trials can be classified under added therapy rather than combination therapy. Effective treatment of AD likely requires targeting multiple mechanisms, such as amyloid-beta (Aβ) and tau pathology. However, many medications face challenges, including poor solubility, low permeability, and the inability to cross the blood- -brain barrier (BBB). This is where nanocarriers come into play, as they can be loaded with these medications to facilitate targeted drug delivery. This approach enhances the pharmacokinetic profile of drugs in both the blood and the brain. Therefore, this paper provides a concise overview of the use of various nanocarriers loaded with drug combinations for treating AD.
{"title":"Prospective Utilization of Nanocarriers Loaded with Drug Combination for Treating Alzheimer's Disease.","authors":"Saif Ahmad Khan, Zufika Qamar, Aashish Rohilla, Pirthi Pal Singh, Suhel Parvez, Sanjula Baboota, Javed Ali","doi":"10.2174/0113816128348877241202053633","DOIUrl":"https://doi.org/10.2174/0113816128348877241202053633","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a debilitating condition that significantly affects the elderly. Early diagnosis is not only critical for improving patient outcomes but also directly influences the success of emerging therapeutic interventions. A therapeutic strategy targeting only one pathogenic mechanism is unlikely to be very effective, as there is increasing evidence that AD does not have a single pathogenic cause. Therefore, combining medications or developing therapies that address multiple pathways may be beneficial. Most clinical trials can be classified under added therapy rather than combination therapy. Effective treatment of AD likely requires targeting multiple mechanisms, such as amyloid-beta (Aβ) and tau pathology. However, many medications face challenges, including poor solubility, low permeability, and the inability to cross the blood- -brain barrier (BBB). This is where nanocarriers come into play, as they can be loaded with these medications to facilitate targeted drug delivery. This approach enhances the pharmacokinetic profile of drugs in both the blood and the brain. Therefore, this paper provides a concise overview of the use of various nanocarriers loaded with drug combinations for treating AD.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001596","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}
Introduction: Chronic Kidney Disease (CKD) is recognized as a major global public health problem. Dialysis is the mainstay of treatment for patients with end-stage renal disease and can prolong survival in patients with CKD. As patient survival increases, the treatment of complications becomes more important. CKD-mineral and bone disorders (CKD-MBD) and renal anemia are common complications in patients with CKD. Cinacalcet is a calcimimetic for the treatment of Secondary Hyperparathyroidism (SHPT) in adult dialysis patients, which regulates the synthesis and secretion of parathyroid hormone by increasing the sensitivity of calcium-sensitive receptors. This retrospective study evaluated the efficacy of cinacalcet in dialysis patients.
Method: Forty-seven patients on dialysis with elevated parathyroid hormone were included. The selected patients have regular follow-up visits in our outpatient clinic and regular use of cinacalcet for no less than 6 months.
Result: During the 6-month efficacy evaluation phase, cinacalcet not only reduced the levels of the intact parathyroid hormone (iPTH, P ≤ 0.05), serum calcium (P ≤ 0.01), and Ca×P (P ≤ 0.05) but also reduced weekly erythropoietin dosage (P ≤ 0.01) and erythropoietin resistance index (ERI, P ≤ 0.05).
Conclusion: While controlling SHPT in patients with CKD, cinacalcet reduced EPO resistance and improved renal anemia. In conclusion, cinacalcet not only decreased the levels of the iPTH, serum calcium, and Ca×P but also reduced weekly EPO dosage and ERI levels. Controlling SHPT in patients with CKD, cinacalcet also reduced ERI and improved renal anemia.
{"title":"Cinacalcet Improves Erythropoietin Resistance in Patients with Secondary Hyperparathyroidism Receiving Dialysis Treatment.","authors":"Wenjuan Weng, Yingjuan Li, Yongda Lin, Jiali Wang, Xiutian Chen, Tianbiao Zhou","doi":"10.2174/0113816128321721241118171041","DOIUrl":"https://doi.org/10.2174/0113816128321721241118171041","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic Kidney Disease (CKD) is recognized as a major global public health problem. Dialysis is the mainstay of treatment for patients with end-stage renal disease and can prolong survival in patients with CKD. As patient survival increases, the treatment of complications becomes more important. CKD-mineral and bone disorders (CKD-MBD) and renal anemia are common complications in patients with CKD. Cinacalcet is a calcimimetic for the treatment of Secondary Hyperparathyroidism (SHPT) in adult dialysis patients, which regulates the synthesis and secretion of parathyroid hormone by increasing the sensitivity of calcium-sensitive receptors. This retrospective study evaluated the efficacy of cinacalcet in dialysis patients.</p><p><strong>Method: </strong>Forty-seven patients on dialysis with elevated parathyroid hormone were included. The selected patients have regular follow-up visits in our outpatient clinic and regular use of cinacalcet for no less than 6 months.</p><p><strong>Result: </strong>During the 6-month efficacy evaluation phase, cinacalcet not only reduced the levels of the intact parathyroid hormone (iPTH, P ≤ 0.05), serum calcium (P ≤ 0.01), and Ca×P (P ≤ 0.05) but also reduced weekly erythropoietin dosage (P ≤ 0.01) and erythropoietin resistance index (ERI, P ≤ 0.05).</p><p><strong>Conclusion: </strong>While controlling SHPT in patients with CKD, cinacalcet reduced EPO resistance and improved renal anemia. In conclusion, cinacalcet not only decreased the levels of the iPTH, serum calcium, and Ca×P but also reduced weekly EPO dosage and ERI levels. Controlling SHPT in patients with CKD, cinacalcet also reduced ERI and improved renal anemia.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001516","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}
Pub Date : 2025-01-13DOI: 10.2174/0113816128345231240925095400
Luis E Simental-Mendía, Mario Simental-Mendía, Claudia I Gamboa-Gómez, Tannaz Jamialahmadi, Amirhossein Sahebkar
Background: In vascular tissue, macrophages and inflammatory cells produce the enzyme lipoprotein- associated phospholipase A2 (Lp-PLA2). Treatment with fibrates decreases Lp-PLA2 levels in individuals with obesity and metabolic syndrome; however, these findings have not been fully clarified.
Objective: The goal of this study was to investigate the possible effects of fibrate therapy on Lp-PLA2 mass and activity through a meta-analysis of clinical trials.
Methods: Web of Science, PubMed, Scopus, Google Scholar, and ClinicalTrials.gov databases were searched using MeSH terms and keywords. Randomized controlled trials (RCT) evaluating the effect of statins on Lp- PLA2 mass and/or activity were included in the meta-analysis. Quantitative data were analyzed using a random- effects model and the generic inverse variance method.
Results: The meta-analysis of 10 clinical trials indicated that fibrate treatment has no significant effect on Lp- PLA2 mass (fibrate vs. placebo/nothing = WMD: -3.29 ng/ml, 95% CI: -21.35, 14.78, p = 0.72; fibrate vs. active control = WMD: -1.08 ng/ml, 95% CI: -51.38, 49.22, p = 0.97); Lp-PLA2 activity (fibrate vs. active control = WMD: 0.84 nmol/ml/min, 95% CI: -0.17, 1.84, p = 0.10); HDL-LpPLA2 activity (fibrate vs. active control = WMD: 0.77 nmol/ml/min, 95% CI: -0.33, 1.88, p = 0.17); and secretory PLA2 (fibrate vs. active control = WMD: 0.37 ng/ml, 95% CI: -1.22, 1.97, p = 0.65). Also, the results of the sensitivity analysis were robust for all these parameters.
Conclusion: In conclusion, fibrate therapy did not reduce the mass and activity of Lp-PLA2.
背景:在血管组织中,巨噬细胞和炎症细胞产生脂蛋白相关磷脂酶A2 (Lp-PLA2)。贝特类药物治疗可降低肥胖和代谢综合征患者的Lp-PLA2水平;然而,这些发现尚未得到充分澄清。目的:本研究的目的是通过临床试验的荟萃分析,探讨贝特治疗对Lp-PLA2质量和活性的可能影响。方法:使用MeSH术语和关键词检索Web of Science、PubMed、Scopus、谷歌Scholar和ClinicalTrials.gov数据库。meta分析纳入了评估他汀类药物对Lp- PLA2质量和/或活性影响的随机对照试验(RCT)。定量数据采用随机效应模型和通用逆方差法进行分析。结果:10项临床试验的荟萃分析显示,贝特治疗对Lp- PLA2质量无显著影响(贝特与安慰剂/无治疗= WMD: -3.29 ng/ml, 95% CI: -21.35, 14.78, p = 0.72;贝特与主动对照= WMD: -1.08 ng/ml, 95% CI: -51.38, 49.22, p = 0.97);Lp-PLA2活性(贝特与主动对照= WMD: 0.84 nmol/ml/min, 95% CI: -0.17, 1.84, p = 0.10);HDL-LpPLA2活性(纤维对照与主动对照= WMD: 0.77 nmol/ml/min, 95% CI: -0.33, 1.88, p = 0.17);分泌PLA2(贝特与主动对照= WMD: 0.37 ng/ml, 95% CI: -1.22, 1.97, p = 0.65)。此外,敏感性分析的结果对所有这些参数都是稳健的。结论:贝特治疗未降低Lp-PLA2的质量和活性。
{"title":"Effect of Fibrates on Lipoprotein-associated Phospholipase A2 Mass and Activity: A Systematic Review and Meta-analysis of Controlled Clinical Trials.","authors":"Luis E Simental-Mendía, Mario Simental-Mendía, Claudia I Gamboa-Gómez, Tannaz Jamialahmadi, Amirhossein Sahebkar","doi":"10.2174/0113816128345231240925095400","DOIUrl":"https://doi.org/10.2174/0113816128345231240925095400","url":null,"abstract":"<p><strong>Background: </strong>In vascular tissue, macrophages and inflammatory cells produce the enzyme lipoprotein- associated phospholipase A2 (Lp-PLA2). Treatment with fibrates decreases Lp-PLA2 levels in individuals with obesity and metabolic syndrome; however, these findings have not been fully clarified.</p><p><strong>Objective: </strong>The goal of this study was to investigate the possible effects of fibrate therapy on Lp-PLA2 mass and activity through a meta-analysis of clinical trials.</p><p><strong>Methods: </strong>Web of Science, PubMed, Scopus, Google Scholar, and ClinicalTrials.gov databases were searched using MeSH terms and keywords. Randomized controlled trials (RCT) evaluating the effect of statins on Lp- PLA2 mass and/or activity were included in the meta-analysis. Quantitative data were analyzed using a random- effects model and the generic inverse variance method.</p><p><strong>Results: </strong>The meta-analysis of 10 clinical trials indicated that fibrate treatment has no significant effect on Lp- PLA2 mass (fibrate vs. placebo/nothing = WMD: -3.29 ng/ml, 95% CI: -21.35, 14.78, p = 0.72; fibrate vs. active control = WMD: -1.08 ng/ml, 95% CI: -51.38, 49.22, p = 0.97); Lp-PLA2 activity (fibrate vs. active control = WMD: 0.84 nmol/ml/min, 95% CI: -0.17, 1.84, p = 0.10); HDL-LpPLA2 activity (fibrate vs. active control = WMD: 0.77 nmol/ml/min, 95% CI: -0.33, 1.88, p = 0.17); and secretory PLA2 (fibrate vs. active control = WMD: 0.37 ng/ml, 95% CI: -1.22, 1.97, p = 0.65). Also, the results of the sensitivity analysis were robust for all these parameters.</p><p><strong>Conclusion: </strong>In conclusion, fibrate therapy did not reduce the mass and activity of Lp-PLA2.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983055","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}
Pub Date : 2025-01-13DOI: 10.2174/0113816128346655241112104045
Asim Najmi
Aims: This study aims to identify and evaluate promising therapeutic proteins and compounds for breast cancer treatment through a comprehensive database search and molecular docking analysis.
Background: Breast cancer (BC), primarily originating from the terminal ductal-lobular unit of the breast, is the most prevalent form of cancer globally. In 2020, an estimated 2.3 million new cases were reported, resulting in approximately 685,000 deaths. Mutations in the BRCA1 and BRCA2 genes are well-established in hereditary breast cancer. The identification of effective therapeutic proteins for BC remains a complex and evolving area of research.
Objective: This study aims to identify and evaluate promising therapeutic proteins and compounds specific to breast cancer through a comprehensive database search and molecular docking analysis.
Methods: A rigorous search was conducted within the National Cancer Institute (NCI), NCI Metathesaurus, SIGnaling Network Open Resource (SIGNOR), Human Protein Atlas (HPA), and the Human Phenotype Ontology (HPO) to shortlist proteins linked to BC (CUI C0678222). Recent studies were reviewed to understand the administration of CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) combined with endocrine therapy for HR-positive and HER2-negative breast cancer. Anticancer compound libraries available at ZINC and PubChem were analyzed. Compounds were evaluated based on their binding energies with CDK4 protein, a rationally selected druggable target.
Results: Key proteins linked to breast cancer were identified through database searches. Proliferation, apoptosis, and G1/S transition pathways were frequently found dysregulated in breast cancer. ZINC13152284 exhibited the strongest binding energy at -10.9 Kcal/mol, followed by ZINC05492794 with a binding energy of -10.4 Kcal/mol. Preexisting drugs showed lower binding energies with the CDK4 protein.
Conclusion: The study highlights the importance of drug repurposing as a strategy for the safe and effective treatment of breast cancer. Synthetic inhibitors often cause severe side effects, emphasizing the need for novel targets and compounds with better therapeutic profiles. Molecular docking identified promising compounds from the ZINC database, suggesting potential new avenues for breast cancer therapy.
目的:本研究旨在通过全面的数据库检索和分子对接分析,鉴定和评价有前景的乳腺癌治疗蛋白和化合物。背景:乳腺癌(BC),主要起源于乳腺末端导管小叶单位,是全球最常见的癌症形式。2020年,估计报告了230万例新病例,导致约68.5万人死亡。BRCA1和BRCA2基因突变在遗传性乳腺癌中是公认的。鉴别治疗BC的有效蛋白仍然是一个复杂和不断发展的研究领域。目的:本研究旨在通过全面的数据库检索和分子对接分析,鉴定和评价有前景的乳腺癌特异性治疗蛋白和化合物。方法:在美国国家癌症研究所(NCI)、NCI meta - thesaurus、信号网络开放资源(SIGNOR)、人类蛋白质图谱(HPA)和人类表型本体(HPO)中进行严格的搜索,以筛选与BC相关的蛋白质(CUI C0678222)。我们回顾了最近的研究,以了解CDK4/6抑制剂(palbociclib, ribociclib, abemaciclib)联合内分泌治疗hr阳性和her2阴性乳腺癌的管理。对ZINC和PubChem网站上现有的抗癌化合物文库进行了分析。化合物是根据其与CDK4蛋白的结合能来评估的,CDK4蛋白是一个合理选择的药物靶点。结果:通过数据库搜索确定了与乳腺癌相关的关键蛋白质。在乳腺癌中,细胞增殖、细胞凋亡和G1/S转化途径经常被发现失调。ZINC13152284的结合能最强,为-10.9 Kcal/mol, ZINC05492794次之,结合能为-10.4 Kcal/mol。先前存在的药物与CDK4蛋白的结合能较低。结论:该研究强调了药物再利用作为一种安全有效治疗乳腺癌的策略的重要性。合成抑制剂通常会引起严重的副作用,因此需要新的靶点和具有更好治疗效果的化合物。分子对接从锌数据库中发现了有希望的化合物,为乳腺癌治疗提供了潜在的新途径。
{"title":"Exploration of Novel Therapeutic Targets for Breast Carcinoma and Molecular Docking Studies of Anticancer Compound Libraries with Cyclin-dependent Kinase 4/6 (CDK4/6): A Comprehensive Study of Signalling Pathways for Drug Repurposing.","authors":"Asim Najmi","doi":"10.2174/0113816128346655241112104045","DOIUrl":"https://doi.org/10.2174/0113816128346655241112104045","url":null,"abstract":"<p><strong>Aims: </strong>This study aims to identify and evaluate promising therapeutic proteins and compounds for breast cancer treatment through a comprehensive database search and molecular docking analysis.</p><p><strong>Background: </strong>Breast cancer (BC), primarily originating from the terminal ductal-lobular unit of the breast, is the most prevalent form of cancer globally. In 2020, an estimated 2.3 million new cases were reported, resulting in approximately 685,000 deaths. Mutations in the BRCA1 and BRCA2 genes are well-established in hereditary breast cancer. The identification of effective therapeutic proteins for BC remains a complex and evolving area of research.</p><p><strong>Objective: </strong>This study aims to identify and evaluate promising therapeutic proteins and compounds specific to breast cancer through a comprehensive database search and molecular docking analysis.</p><p><strong>Methods: </strong>A rigorous search was conducted within the National Cancer Institute (NCI), NCI Metathesaurus, SIGnaling Network Open Resource (SIGNOR), Human Protein Atlas (HPA), and the Human Phenotype Ontology (HPO) to shortlist proteins linked to BC (CUI C0678222). Recent studies were reviewed to understand the administration of CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) combined with endocrine therapy for HR-positive and HER2-negative breast cancer. Anticancer compound libraries available at ZINC and PubChem were analyzed. Compounds were evaluated based on their binding energies with CDK4 protein, a rationally selected druggable target.</p><p><strong>Results: </strong>Key proteins linked to breast cancer were identified through database searches. Proliferation, apoptosis, and G1/S transition pathways were frequently found dysregulated in breast cancer. ZINC13152284 exhibited the strongest binding energy at -10.9 Kcal/mol, followed by ZINC05492794 with a binding energy of -10.4 Kcal/mol. Preexisting drugs showed lower binding energies with the CDK4 protein.</p><p><strong>Conclusion: </strong>The study highlights the importance of drug repurposing as a strategy for the safe and effective treatment of breast cancer. Synthetic inhibitors often cause severe side effects, emphasizing the need for novel targets and compounds with better therapeutic profiles. Molecular docking identified promising compounds from the ZINC database, suggesting potential new avenues for breast cancer therapy.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983058","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}
Pub Date : 2025-01-13DOI: 10.2174/0113816128347041241129055001
Francesco Saverio Ragusa, Nicola Veronese, Stefano Ciriminna, Diletta Agnello, Rosella Capitummino, Chiara Cavaleri, Alessandro D'Aleo, Chiara Maria Errera, Maria Chiara Garlisi, Chiara Giannettino, Alessandra Lo Nigro, Sofia Elena Montana Lampo, Ottavia Giovanna Plano, Gerlando Speziale, Pascal Roberto Titone, Mario Barbagallo, Ligia J Dominguez
Background: In recent years, sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as a valuable treatment for type 2 diabetes (T2D) and heart failure. Despite these medications seeming to be safe in older people, the literature about SGLT2i and frailty is still limited. This study aims to evaluate whether SGLT2i use is associated with increased survival in older adults and if frailty can affect the findings.
Material and methods: We enrolled over 65 patients admitted to the Geriatrics Wards at the University Hospital 'P. Giaccone' in Palermo, Italy, between December 2022 and May 2023. After 12 months of follow-up, various outcomes were assessed, including mortality, hospitalization, glycemic dysregulation, urinary tract infections, and falls. The association between SGLT2i use and mortality was analyzed and reported as hazard ratios (HRs) with their 95% confidence intervals (CIs).
Results: A total of 80 patients were included in the study (mean age 79.5 ± 8.5 years; 50% were women). Patients using SGLT2i had a higher prevalence of T2D (p = 0.02) and cirrhosis (p = 0.001). After adjusting for potential confounders, SGLT2i use was significantly associated with a reduced mortality risk (HR = 0.53; 95% CI: 0.20-0.93; p = 0.02). When stratified by the presence of multidimensional frailty, SGLT2i use was significantly associated with a lower risk of mortality in frail patients (HR = 0.27; 95% CI: 0.06-0.88; p = 0.008), but not in robust ones.
Conclusion: In older frail patients, the use of SGLT2i is associated with reduced mortality after 12 months of follow-up. Further larger studies are needed to evaluate the role of these medications in older adults.
{"title":"Use of SGLT2 Inhibitors in Frail Older Adults is Associated with Increased Survival: A Retrospective Study.","authors":"Francesco Saverio Ragusa, Nicola Veronese, Stefano Ciriminna, Diletta Agnello, Rosella Capitummino, Chiara Cavaleri, Alessandro D'Aleo, Chiara Maria Errera, Maria Chiara Garlisi, Chiara Giannettino, Alessandra Lo Nigro, Sofia Elena Montana Lampo, Ottavia Giovanna Plano, Gerlando Speziale, Pascal Roberto Titone, Mario Barbagallo, Ligia J Dominguez","doi":"10.2174/0113816128347041241129055001","DOIUrl":"https://doi.org/10.2174/0113816128347041241129055001","url":null,"abstract":"<p><strong>Background: </strong>In recent years, sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as a valuable treatment for type 2 diabetes (T2D) and heart failure. Despite these medications seeming to be safe in older people, the literature about SGLT2i and frailty is still limited. This study aims to evaluate whether SGLT2i use is associated with increased survival in older adults and if frailty can affect the findings.</p><p><strong>Material and methods: </strong>We enrolled over 65 patients admitted to the Geriatrics Wards at the University Hospital 'P. Giaccone' in Palermo, Italy, between December 2022 and May 2023. After 12 months of follow-up, various outcomes were assessed, including mortality, hospitalization, glycemic dysregulation, urinary tract infections, and falls. The association between SGLT2i use and mortality was analyzed and reported as hazard ratios (HRs) with their 95% confidence intervals (CIs).</p><p><strong>Results: </strong>A total of 80 patients were included in the study (mean age 79.5 ± 8.5 years; 50% were women). Patients using SGLT2i had a higher prevalence of T2D (p = 0.02) and cirrhosis (p = 0.001). After adjusting for potential confounders, SGLT2i use was significantly associated with a reduced mortality risk (HR = 0.53; 95% CI: 0.20-0.93; p = 0.02). When stratified by the presence of multidimensional frailty, SGLT2i use was significantly associated with a lower risk of mortality in frail patients (HR = 0.27; 95% CI: 0.06-0.88; p = 0.008), but not in robust ones.</p><p><strong>Conclusion: </strong>In older frail patients, the use of SGLT2i is associated with reduced mortality after 12 months of follow-up. Further larger studies are needed to evaluate the role of these medications in older adults.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983080","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}
Pub Date : 2025-01-10DOI: 10.2174/0113816128330516241121150719
Fanxianzi Meng, Zhichao Liu, Shucun Qin, Boyan Liu
Molecular hydrogen (H2) is considered a biological antioxidant. Hydrogen-rich Water (HRW) is regular water that contains dissolved H2 and has become more widely used in recent years. This review summarizes the basic research and clinical applications of HRW consumption to support its use for daily health and clinical treatment. The biological effects of HRW include reducing oxidative stress, exerting antiinflammatory effects, regulating glucose and lipid metabolism, protecting mitochondrial function, and regulating apoptosis. Hypotheses about the mechanisms of H2 include the direct scavenging of toxic free radicals, the Fe-porphyrin biosensor hypothesis, the effect of H2 on biological enzymes, the lipoprotein regulation of H2, and H2 acting on the intestinal barrier. Clinically, HRW has been used for adjuvant treatment, disease prevention, and quality of life improvement. In the future, more in-depth studies and large-scale clinical trials are needed.
{"title":"Oral Administration of Hydrogen-rich Water: Biomedical Activities, Potential Mechanisms, and Clinical Applications.","authors":"Fanxianzi Meng, Zhichao Liu, Shucun Qin, Boyan Liu","doi":"10.2174/0113816128330516241121150719","DOIUrl":"https://doi.org/10.2174/0113816128330516241121150719","url":null,"abstract":"<p><p>Molecular hydrogen (H2) is considered a biological antioxidant. Hydrogen-rich Water (HRW) is regular water that contains dissolved H2 and has become more widely used in recent years. This review summarizes the basic research and clinical applications of HRW consumption to support its use for daily health and clinical treatment. The biological effects of HRW include reducing oxidative stress, exerting antiinflammatory effects, regulating glucose and lipid metabolism, protecting mitochondrial function, and regulating apoptosis. Hypotheses about the mechanisms of H2 include the direct scavenging of toxic free radicals, the Fe-porphyrin biosensor hypothesis, the effect of H2 on biological enzymes, the lipoprotein regulation of H2, and H2 acting on the intestinal barrier. Clinically, HRW has been used for adjuvant treatment, disease prevention, and quality of life improvement. In the future, more in-depth studies and large-scale clinical trials are needed.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983061","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}
Hemophilia A (HA) is an inherited condition that is characterized by a lack of coagulation factor VIII (FVIII), which is needed for blood clotting. To produce recombinant factor VIII (rFVIII) for treatment, innovative methods are required. This study presents a thorough examination of the genetic engineering and biotechnological methods that are essential for the production of this complex process. Multiple host cells, such as animal, microbial, and human cell lines, are examined. Cultivating genetically modified cells enables the production of rFVIII, with further changes after protein synthesis, such as glycosylation, taking place in eukaryotic cells to guarantee correct folding. The extraction and purification of rFVIII require advanced methods, including affinity chromatography, to improve the purity of the protein. The purified protein undergoes rigorous quality control, which includes Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDSPAGE) analysis, to assess its identity, purity, and functioning. The scalability of this approach allows for the synthesis of significant amounts of rFVIII for therapeutic purposes. Optimization strategies include modifying B-domain-deleted (BDD) FVIII, including introns in FVIII complementary DNA (cDNA) sequences to boost synthesis and storage, and making changes to chaperone-binding areas to optimize protein release. Furthermore, the search for a modified form of FVIII that has a longer duration of action in the body shows potential for enhancing the effectiveness of synthetic FVIII and progressing the treatment of hemophilia A. Future research should focus on improving the treatment of hemophilia A by developing a variant of FVIII that has increased stability and reduced immunogenicity.
{"title":"A Comparative Review on the Production of Factor VIII in Human and Non-human Hosts.","authors":"Amirhossein Ghaemi, Hamid Moghimi, Mohammad-Hossein Sarrafzadeh","doi":"10.2174/0113816128327353241121050134","DOIUrl":"https://doi.org/10.2174/0113816128327353241121050134","url":null,"abstract":"<p><p>Hemophilia A (HA) is an inherited condition that is characterized by a lack of coagulation factor VIII (FVIII), which is needed for blood clotting. To produce recombinant factor VIII (rFVIII) for treatment, innovative methods are required. This study presents a thorough examination of the genetic engineering and biotechnological methods that are essential for the production of this complex process. Multiple host cells, such as animal, microbial, and human cell lines, are examined. Cultivating genetically modified cells enables the production of rFVIII, with further changes after protein synthesis, such as glycosylation, taking place in eukaryotic cells to guarantee correct folding. The extraction and purification of rFVIII require advanced methods, including affinity chromatography, to improve the purity of the protein. The purified protein undergoes rigorous quality control, which includes Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDSPAGE) analysis, to assess its identity, purity, and functioning. The scalability of this approach allows for the synthesis of significant amounts of rFVIII for therapeutic purposes. Optimization strategies include modifying B-domain-deleted (BDD) FVIII, including introns in FVIII complementary DNA (cDNA) sequences to boost synthesis and storage, and making changes to chaperone-binding areas to optimize protein release. Furthermore, the search for a modified form of FVIII that has a longer duration of action in the body shows potential for enhancing the effectiveness of synthetic FVIII and progressing the treatment of hemophilia A. Future research should focus on improving the treatment of hemophilia A by developing a variant of FVIII that has increased stability and reduced immunogenicity.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983067","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}
Background: The metal oxide nanoparticles possess unique properties such as biological compatibility, superior reactivity, and capacity to develop reactive oxygen species, due to this they have drawn significant interest in cancer treatment. The various MONPs such as cerium oxide, Copper oxide, Iron oxide, Titanium dioxide, and Zinc oxide have been investigated for several types of cancers including brain, breast, cervical, colon, leukemia, liver, lung, melanoma, ovarian, and prostate cancers. However, traditional physiochemical synthetic methods for MONPs commonly include toxic materials, a major concern that raises questions regarding their biocompatibility and safety.
Objective: This study aims to investigate the role of plant phytoconstituents in the development of MONPs via green synthesis and explore the therapeutic effectiveness of MONPs in treating several types of cancer. Primarily, it examines the potential of plant phytoconstituents (phenolic compounds, flavonoids, glycosides, alkaloids, etc.) in the development of MONPs as well as their improved ability to target numerous types of cancer.
Methods: A systemic search was conducted on recent literature, focusing on developing green MONPs by utilizing plants' phytoconstituents (plant extracts). The study of plant phytochemicals (present in different parts of a plant such as leaves, flowers, stems, peels, and roots) and their role in the synthesis of green metal oxide nanoparticles as well as their anticancer activity against several types of cancers was analyzed. Also focusing on their anticancer mechanism that involves ROS production, generates oxidative stress, and apoptosis leads to cancer inhibition.
Results: Phytochemicals-mediated metal oxide nanoparticle synthesis revealed many advantages such as improved biological compatibility and enhanced sensitivity towards cancer cells. Phytochemicals present in plant extracts act as natural capping, reducing, and stabilizing agents, enhancing nanoparticle synthesis which leads to synergistic anticancer activity. Additionally, the natural antioxidant and anticancer activity of various phytochemicals enhances the therapeutic potential of metal oxide nanoparticles, producing them more effective against ROS-generated apoptosis and showing negligible toxicity towards normal cells.
Conclusion: The utilization of plant phytochemicals in metal oxide nanoparticle production presents a safe, eco-friendly, sustainable, and effective approach to developing effective and safer cancer nanomedicines. Green synthesis not only increases anticancer activity but also decreases the biocompatibility problems associated with the physiochemical synthetic approach. Further research needs to concentrate on improving this synergy to create a targeted phytochemical-based metal oxide nanoparticle for cancer therapeutics.
{"title":"Utilizing Plant Phytoconstituents in Metal Oxide Nanoparticle Synthesis for Cancer Therapies.","authors":"Swati Dubey, Tarun Virmani, Shiv Kumar Yadav, Girish Kumar, Ashwani Sharma, Dalapathi Gugulothu","doi":"10.2174/0113816128329342241120105041","DOIUrl":"https://doi.org/10.2174/0113816128329342241120105041","url":null,"abstract":"<p><strong>Background: </strong>The metal oxide nanoparticles possess unique properties such as biological compatibility, superior reactivity, and capacity to develop reactive oxygen species, due to this they have drawn significant interest in cancer treatment. The various MONPs such as cerium oxide, Copper oxide, Iron oxide, Titanium dioxide, and Zinc oxide have been investigated for several types of cancers including brain, breast, cervical, colon, leukemia, liver, lung, melanoma, ovarian, and prostate cancers. However, traditional physiochemical synthetic methods for MONPs commonly include toxic materials, a major concern that raises questions regarding their biocompatibility and safety.</p><p><strong>Objective: </strong>This study aims to investigate the role of plant phytoconstituents in the development of MONPs via green synthesis and explore the therapeutic effectiveness of MONPs in treating several types of cancer. Primarily, it examines the potential of plant phytoconstituents (phenolic compounds, flavonoids, glycosides, alkaloids, etc.) in the development of MONPs as well as their improved ability to target numerous types of cancer.</p><p><strong>Methods: </strong>A systemic search was conducted on recent literature, focusing on developing green MONPs by utilizing plants' phytoconstituents (plant extracts). The study of plant phytochemicals (present in different parts of a plant such as leaves, flowers, stems, peels, and roots) and their role in the synthesis of green metal oxide nanoparticles as well as their anticancer activity against several types of cancers was analyzed. Also focusing on their anticancer mechanism that involves ROS production, generates oxidative stress, and apoptosis leads to cancer inhibition.</p><p><strong>Results: </strong>Phytochemicals-mediated metal oxide nanoparticle synthesis revealed many advantages such as improved biological compatibility and enhanced sensitivity towards cancer cells. Phytochemicals present in plant extracts act as natural capping, reducing, and stabilizing agents, enhancing nanoparticle synthesis which leads to synergistic anticancer activity. Additionally, the natural antioxidant and anticancer activity of various phytochemicals enhances the therapeutic potential of metal oxide nanoparticles, producing them more effective against ROS-generated apoptosis and showing negligible toxicity towards normal cells.</p><p><strong>Conclusion: </strong>The utilization of plant phytochemicals in metal oxide nanoparticle production presents a safe, eco-friendly, sustainable, and effective approach to developing effective and safer cancer nanomedicines. Green synthesis not only increases anticancer activity but also decreases the biocompatibility problems associated with the physiochemical synthetic approach. Further research needs to concentrate on improving this synergy to create a targeted phytochemical-based metal oxide nanoparticle for cancer therapeutics.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946104","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}
Pub Date : 2025-01-07DOI: 10.2174/0113816128336901241125092132
Rohit Kumar, Sucharitha Bai, Rahul Shukla, Saba Naqvi
Scutellarein, a flavone found in the perennial herb Scutellaria baicalensis, has a wide range of pharmacological actions, such as antioxidant, anti-inflammatory, and neuroprotective. Increasing evidence has emphasized the developing significance of scutellarein in several neurological illnesses, such as Alzheimer's and Parkinson's disease, cerebral ischemia, and neuroblastoma. This review is centered on the molecular processes that underlie the neuroprotective properties of scutellarein in various neurological disorders, as indicated by recent pre-clinical research. Furthermore, it critically examines the potential challenges and advantages of scutellarein inclusion within the range of treatments for neurological disorders.
{"title":"Therapeutic Role of Scutellarein in Neurological Disorders.","authors":"Rohit Kumar, Sucharitha Bai, Rahul Shukla, Saba Naqvi","doi":"10.2174/0113816128336901241125092132","DOIUrl":"https://doi.org/10.2174/0113816128336901241125092132","url":null,"abstract":"<p><p>Scutellarein, a flavone found in the perennial herb Scutellaria baicalensis, has a wide range of pharmacological actions, such as antioxidant, anti-inflammatory, and neuroprotective. Increasing evidence has emphasized the developing significance of scutellarein in several neurological illnesses, such as Alzheimer's and Parkinson's disease, cerebral ischemia, and neuroblastoma. This review is centered on the molecular processes that underlie the neuroprotective properties of scutellarein in various neurological disorders, as indicated by recent pre-clinical research. Furthermore, it critically examines the potential challenges and advantages of scutellarein inclusion within the range of treatments for neurological disorders.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946099","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}
Pub Date : 2025-01-07DOI: 10.2174/0113816128339561241120135914
Carlo Cervellati, Alessandro Trentini, Marco Zuin, Gianmarco Mola, Raffaella Riccetti, Cristina Manfrinato, Domenico Sergi, Gerhard Multhaup, Giovanni Zuliani
Amyloid beta (Aβ) dyshomeostasis is considered the main biological aberration in Alzheimer's Disease (AD) pathology. The interplay between Aβ formation and clearance is predominantly modulated by a disintegrin and a metalloproteinase 10 (ADAM10, α-secretase) and β-site APP Cleaving Enzyme 1 (BACE1), the two pivotal enzymes in both non-amyloidogenic/amyloidogenic and amyloidolytic pathways. Emerging evidence suggests that aberrations in ADAM10 and BACE1 expression, activity, and function in the brain of AD patients also manifest in peripheral fluids, suggesting their potential as blood-based biomarkers for AD diagnosis. This review provides a comprehensive overview of the literature by exploring the roles of ADAM10 and BACE1 in AD, spanning from their involvement as pathological AD drivers to their potential utility as promising biomarkers.
{"title":"BACE-1 and ADAM-10 as Potential Peripheral Biomarkers for Alzheimer's Disease.","authors":"Carlo Cervellati, Alessandro Trentini, Marco Zuin, Gianmarco Mola, Raffaella Riccetti, Cristina Manfrinato, Domenico Sergi, Gerhard Multhaup, Giovanni Zuliani","doi":"10.2174/0113816128339561241120135914","DOIUrl":"https://doi.org/10.2174/0113816128339561241120135914","url":null,"abstract":"<p><p>Amyloid beta (Aβ) dyshomeostasis is considered the main biological aberration in Alzheimer's Disease (AD) pathology. The interplay between Aβ formation and clearance is predominantly modulated by a disintegrin and a metalloproteinase 10 (ADAM10, α-secretase) and β-site APP Cleaving Enzyme 1 (BACE1), the two pivotal enzymes in both non-amyloidogenic/amyloidogenic and amyloidolytic pathways. Emerging evidence suggests that aberrations in ADAM10 and BACE1 expression, activity, and function in the brain of AD patients also manifest in peripheral fluids, suggesting their potential as blood-based biomarkers for AD diagnosis. This review provides a comprehensive overview of the literature by exploring the roles of ADAM10 and BACE1 in AD, spanning from their involvement as pathological AD drivers to their potential utility as promising biomarkers.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946085","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}