Current Pharmaceutical Design - Volume 31, Issue 19, 2025
Volume 31, Issue 19, 2025
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Epigenetics Modulators as Therapeutics for Neurological Disorders
Epigenetics mechanisms play a crucial role in regulating gene expression and cellular function in the development and progression of neurological disorders. Emerging evidence suggests that dysregulation of these epigenetic processes contributes significantly to the pathogenesis of various neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy. Epigenetic mechanisms, including DNA methylation, histone modification, and non-coding RNAs, significantly impact neural plasticity. The use of epigenetic modulators, including DNA methyltransferase and histone deacetylase inhibitors, offers a promising strategy to correct and modify aberrant epigenetic marks, potentially restoring neurological homeostasis. This review highlights recent research findings from ongoing clinical trials and the potential benefits and challenges of epigenetic therapies for neurological disorders. We discuss the capacity of these interventions to potentially halt or reverse disease progression, their targeted nature, and their neuroprotective effects. Additionally, we address the hurdles facing the field, including issues of specificity, delivery, and long-term efficacy.
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Advances in the Synthesis and SAR of Pyrido[2,3-d]pyrimidine Scaffold
Authors: Xiongpiao Wei, Dang Fan, Haifeng Dong, Min Li, Qiaoli Lv, Pengwu Zheng and Linxiao WangPyrido[2,3-d]pyrimidine and its derivatives have garnered significant attention due to their potential biological and pharmacological activities. Research has demonstrated their significant potential for antitumor and antibacterial applications. Over the years, pyrido[2,3-d]pyrimidine derivatives have remained a research focus for scientists, with numerous synthetic methods and reaction conditions reported. This review comprehensively summarizes the fast, facile, and economical synthetic methods for pyrido[2,3-d]pyrimidine derivatives over the past years, which are categorized based on different synthetic precursors, and evaluates their antitumor and antibacterial activities, aiming to make them better serve the cause of human health.
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Oral Administration of Hydrogen-rich Water: Biomedical Activities, Potential Mechanisms, and Clinical Applications
Authors: Fanxianzi Meng, Zhichao Liu, Shucun Qin and Boyan LiuMolecular 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 anti-inflammatory 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.
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Crosstalk: Biochemical Signatures and Clinical Implications in Rare Hereditary Hemolytic Anemias (Hereditary Spherocytosis)
BackgroundClinical Hereditary Hemolytic Anemia (HAA) particularly Hereditary Spherocytosis (HS) encompasses diverse genetic disorders causing premature red blood cell destruction and intrinsic RBC defects. There’s a pressing need for standardized diagnostic protocols tailored to the Asian population, particularly in Saudi Arabia, underscoring the significance of thorough blood biochemistry analysis.
Materials and MethodsA case-control prospective study was conducted at King Abdulaziz University, samples were obtained from King Fahad Hospital, Jeddah, Saudi Arabia, serving a significant population, and blood samples from 27 patients meeting ethical criteria for HHA and HS. Inclusion criteria included diagnosed patients of any age and sex, while exclusion criteria encompass chronic infections, metabolic diseases, pregnancy, and lactation. Blood profiling was conducted following strict protocols, aiming to glean insights into patients’ management and therapeutic strategies. Despite an intended larger sample size, limitations in availability led to the inclusion of 27 patient analyses.
ResultsAmong 27 participants, males comprised 59.3%, females 40.7%. Anemia types indicated 22.2% Type 1 (HHA) and 77.8% Type 3 (HS). Age groups (<30, 31-59, ≥60 years) highlighted HS prevalence, notably in older individuals. Blood pressure analysis revealed age-related increases, especially in those over 60 with systolic BP (147.33 ± 9.86 mm/Hg) (p≤0.02) and diastolic BP (85.67 ± 9.01 mm/Hg) (p≤0.03) emphasizing age-specific monitoring. Temperature variations were noted across ages, significant in patients over 60 (35.93 ± 1.100C) (p≤0.09), indicating potential clinical relevance. Iron levels showed no age-related differences, while Blood Urea Nitrogen (BUN) levels rose with age, particularly in those over 60 (35.83 ± 16.67 mm/dL) (p≤0.04), suggesting age-related influence. Alkaline Phosphatase levels increased with age, especially in patients aged 31 to 59 (205.80 ± 123.17IU/L)(p≤0.001), warranting further investigation. Similarly, Aspartate Transferase levels rose with age, especially in patients aged 31 to 59 (134.69 ± 284.58 U/L) (p≤0.01), underlining age-specific considerations. Notable differences in BUN (15.03 mm/dL and 29.06 mm/dL) and Aspartate Transferase (33.01 U/L and 115.66 U/L) levels were observed among different anemia types with no major significant alteration in LDH.
ConclusionThe results suggest unique biochemical signatures with potential renal and hepatic implications, underscoring the importance of biochemical assessment in managing hereditary hemolytic anemias, particularly HS.
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Network Pharmacology, Molecular Docking, Molecular Dynamics to Explore the Mechanism of Danggui Shaoyao Powder for Hepatic Encephalopathy
Authors: Miao Zhang, Rongxin Liu, Yusen Zhao, Zixin Chen, Honglin Zhai and Hongzong SiBackgroundPatients with hepatic encephalopathy (HE) have many triggers and a high mortality rate. The protective effect of existing therapeutic drugs on the liver is weak. We found that Danggui Shaoyao Powder can improve the symptoms of HE and may have a better liver protection effect. And the mechanism of it is unclear.
ObjectiveThe research explores the mechanism of Danggui Shaoyao Powder for the treatment of HE through network pharmacology, molecular docking and molecular dynamics.
MethodsTargets of Danggui Shaoyao Powder were screened from Traditional Chinese Medicine System Pharmacology Platform (TCMSP), SwissTargetPrediction, and Uniport. GeneCards was used to gain targets of HE. Further, core targets and ingredients were screened by protein-protein interaction network (PPI) and herbs-compounds-targets network. Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were completed to screen relative sites and signaling pathways. Molecular docking and dynamics were used to show the stability of ligand-receptor complexes.
ResultsIL6, SRC and kaempferol, beta-sitosterol were screened as the top two core targets and ingredients. Dendrites, dendritic trees, and membrane sides were defined as the main sites of action. Core signaling pathways were screened such as: PI3K-Akt and MAPK. Molecular docking shows well-defined binding sites and the stability of the binding is demonstrated by molecular dynamics.
ConclusionThrough this study, Danggui Shaoyao Powder may act on IL6, SRC, and other targets through ingredients such as kaempferol and beat-sitosterol and regulate signaling pathways such as PI3K-Akt, MAPK and NF-κB to the treatment of HE.
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Volumes & issues
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Volume 31 (2025)
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Volume (2025)
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Volume 30 (2024)
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Volume 29 (2023)
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Volume 28 (2022)
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Volume 27 (2021)
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Volume 26 (2020)
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Volume 25 (2019)
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Volume 24 (2018)
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Volume 23 (2017)
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Volume 22 (2016)
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Volume 21 (2015)
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Volume 20 (2014)
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Volume 19 (2013)
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Volume 18 (2012)
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Volume 17 (2011)
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Volume 16 (2010)
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Volume 15 (2009)
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Volume 14 (2008)
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Volume 13 (2007)
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Volume 12 (2006)
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Volume 11 (2005)
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Volume 10 (2004)
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Volume 9 (2003)
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Volume 8 (2002)
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Volume 7 (2001)
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Volume 6 (2000)
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