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  5. Volume 30, Issue 33, 2024

Current Pharmaceutical Design - Volume 30, Issue 33, 2024

Volume 30, Issue 33

Volume 30, Issue 33, 2024

    • Role of Biosynthesis and Catabolism of Neurotransmitters in Drug Discovery for Anxiety and Depression

      https://doi.org/10.2174/0113816128309913240704095334

      The purpose of this review is to correlate the probable causes of anxiety disorders with the imbalance of neurotransmitters in the brain and also highlight the drugs for these mental disorders that have been discovered based on the biosynthesis and catabolism of these brain chemicals. Peer-reviewed journal’s articles, news and books published in English between 1997 and 2023 describing the role of neurotransmitters in anxiety disorders were searched in Google Scholar, Research Gate and PubMed databases. The contents were carefully analyzed by the authors and understood and compiled to build a concise perspective on the role of biosynthesis and catabolism of neurotransmitters in anxiety and depression. Anxiety disorders are reported to be common patterns of psychological symptoms that impact multiple areas of life. Anxiety and depression are prevalent worldwide and are significantly contributing towards the global health burden. Genetic determinants are believed to play an important role in these disorders. According to modern medicine, one of the most important aspects that is known to be crucial for these disorders is the imbalance of neurotransmitters in the brain. The biosynthesis and catabolism of neurotransmitters have been extensively targeted for innovative drug discovery approaches at various steps that have led to the discovery of many drugs for these psychological disorders. The biosynthetic and catabolic reaction cycles of neurotransmitters and the discovery of drugs based on these hypotheses are discussed. To the best of the authors’ knowledge, this review compiles already known descriptive knowledge on “relation of neurotransmitter imbalance with anxiety disorders” in a precise way that will provide readers with an overview of the vast literature.

    • Diuretic Combination Therapy in Acute Heart Failure: An Updated Review

      https://doi.org/10.2174/0113816128316596240625110337

      Loop diuretics are the cornerstone of decongestive therapy in patients presenting with acute heart failure and have been extensively studied in randomized clinical trials. Therefore, in current guidelines, they are the only drug with a class I recommendation to treat signs and symptoms of congestion when present. However, the percentage of patients achieving successful decongestion is suboptimal, and diuretic resistance frequently develops. Patients with a poor response to loop diuretics and those discharged with residual signs of congestion are characterized by a worse prognosis over time. Recently, a renovated interest in different diuretic classes sprouted among heart failure researchers in order to improve decongestion strategies and ameliorate short- and long-term clinical outcomes. Randomized clinical trials investigating associations among diuretic classes and loop diuretics have been performed but yielded variable results. Therefore, despite initial evidence of a possible benefit from some of these compounds, a definite way to approach diuretic resistance diuretic combination therapy is still missing. The aim of this review is to summarize current clinical evidence on the use of diuretic combination therapy in patients with acute heart failure and to suggest a possible approach to avoid or counteract diuretic resistance.

    • Shape Dependent Therapeutic Potential of Nanoparticulate System: Advance Approach for Drug Delivery

      https://doi.org/10.2174/0113816128314618240628110218

      Drug delivery systems rely heavily on nanoparticles because they provide a targeted and monitored release of pharmaceuticals that maximize therapeutic efficacy and minimize side effects. To maximize drug internalization, this review focuses on comprehending the interactions between biological systems and nanoparticles. The way that nanoparticles behave during cellular uptake, distribution, and retention in the body is determined by their shape. Different forms, such as mesoporous silica nanoparticles, micelles, and nanorods, each have special properties that influence how well drugs are delivered to cells and internalized. To achieve the desired particle morphology, shape-controlled nanoparticle synthesis strategies take into account variables like pH, temperatures, and reaction time. Top-down techniques entail dissolving bulk materials to produce nanoparticles, whereas bottom-up techniques enable nanostructures to self-assemble. Comprehending the interactions at the bio-nano interface is essential to surmounting biological barriers and enhancing the therapeutic efficacy of nanotechnology in drug delivery systems. In general, drug internalization and distribution are greatly influenced by the shape of nanoparticles, which presents an opportunity for tailored and efficient treatment plans in a range of medical applications.

    • Nanotechnological Advances in the Diagnosis of Gynecological Cancers and Nanotheranostics

      https://doi.org/10.2174/0113816128317605240628063731

      Gynecological cancers are one of the main causes of female mortality worldwide. Despite the various strategies to reduce mortality and improve quality of life, there are still many deficiencies in the diagnosis and treatment of gynecological cancers. One of the important steps to ensure optimal cancer treatment is the early detection of cancer cells and the use of drugs to reduce toxicity. Due to the increase in systemic toxicity and resistance to traditional and conventional diagnostic methods, new strategies, including nanotechnology, are being used to improve diagnosis and reduce the severity of the disease. Nanoparticles (NPs) provide exciting opportunities to improve Gynecological Cancers (GCs) diagnosis, particularly in the initial stages. In biomedical investigations and clinical settings, NPs can be used to increase the sensitivity and specificity of recognition and/or imaging of GCs with the help of their molecular and cellular processes. To design more efficient diagnostic NPs for gynecological cancer cells or tissues, determining the specific biomarkers is of great importance. NP-based imaging agents are another solution to trace cancer cells. This review highlights the potential of some NP-based diagnostic techniques in GC detection, which could be translated to clinical settings to improve patient care.

    • Impact of Tyrosine Kinase Inhibitors (TKIs) on Growth in Children and Adolescents with Chronic Myeloid Leukemia: A Systematic Review

      https://doi.org/10.2174/0113816128309071240626114308
      Background

      Chronic Myeloid Leukemia (CML) is a rare myeloproliferative disease in childhood. Treatment in CML includes Tyrosine Kinase Inhibitors (TKIs), which inhibit the cytoplasmic kinase BCR/ABL. Tyrosine kinases play a key role in the secretion of growth hormone and insulin-like growth factor 1 (IGF-1).

      Objective

      The aim of this systematic review was to study the effect of TKIs on the growth of children and adolescents with CML.

      Methods

      English-language publications were searched in the PubMed/Cochrane library/Google Scholar databases (2002-2023), and retrieved studies were assessed according to PRISMA-Statement and Newcastle-Ottawa-scale.

      Results

      The search strategy yielded 1066 articles. After applying the inclusion/exclusion criteria, 941 were excluded based on title screening and 111 on abstract review. The systematic review included 14 articles (11 retrospective observational studies/3 clinical trials). Twelve studies reported data on the prevalence of growth disorders after the administration of 1st generation TKIs (imatinib). Two studies reported a negative effect of 2nd generation TKIs (dasatinib/nilotinib) on physical growth. Four studies recorded a decrease in height z-score after treatment compared to baseline. Two 1st-generation TKIs studies reported data on children's final height; one reported restoration of final height to normal after the onset of puberty, despite initial slowing, and the final height was lower than mid-parental target height. Serum IGF-1 levels were reported in 2 studies to be within normal range, while in 3 studies, a significant decrease was documented. Considerable study heterogeneity was observed related to dosage/duration of treatment/disease phase/stage of puberty/ethnicity.

      Conclusion

      A negative effect of TKIs on the growth and final height of children was noted.

    • Efficacy and Mechanism of Core Traditional Chinese Medicines for Treating Malignant Lymphoma based on Efficacy Studies: A Study Supported by Network Pharmacology and Molecular Docking

      https://doi.org/10.2174/0113816128308565240710114350
      Background

      The burden of malignant lymphoma in China is greater than the global equivalent. The randomized controlled trials provide medical evidence that TCM can improve the response and survival in patients with lymphoma. However, the mechanisms underlying remain undefined.

      Objective

      Evidence-based data mining for traditional Chinese medicine (TCM) on improving response and survival in malignant lymphoma treatment was performed in this study. In addition, the mechanisms of TCM through network pharmacology and molecular docking were explored.

      Methods

      The China national knowledge infrastructure, Wanfang Data, China Science and Technology Journal Database, PubMed, and Web of Science databases were searched to select TCM formulas with response and survival benefits in the treatment of malignant lymphomas. We then analyzed and visualized the tropism of taste, frequency of drug use, dosage, clustering, association rules mining (minimum support threshold as 0.20, the minimum confidence threshold as 0.80 and lift >1), and complex networks for potential core herb compositions using Excel, IBM SPSS Statistics 26, and IBM SPSS Modeler 18. TCM systems pharmacology, GeneCards, Online Mendelian Inheritance in Man, and other databases were used to screen potential core active ingredients and malignant lymphoma-related targets. The intersection targets were used to construct a protein interaction network using Cytoscape to obtain the key targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment were used to analyze the core target, and molecular docking of key components and targets was performed using CB-Dock2.

      Results

      Twenty-four Chinese herbal formulae were included, encompassing 107 herbs with mainly cold and warm properties and bitter and sweet flavors. They were associated with the yin meridians of the liver, spleen, and lungs. The TCMs underwent association rule analysis, identified 27 association rules, including 12 herb pairs and 13 angle medicine, and clustered into eight classes by clustering analysis. Combined with the results from mining analysis, Pinelliae (Ban-xia), Poria (Fu-ling), Atractylodis macrocephalae (Bai-zhu), Curcumae (E-zhu), and Sparganii (San-leng) were the potential core herbs According to network pharmacology and molecular docking, the main core components of the potential core drugs are hederagenin, cerevisterol, 14-acetyl-12-senecioyl-2E,8E,10E-atractylentriol, 12,13-epoxy-9-hydroxynonadeca-7,10-dienoic acid, cavidine, and baicalein. These core drugs are mainly involved in the pathways of EGFR tyrosine kinase inhibitor resistance, PD-1/L1, natural killer cell-mediated cytotoxicity, NF-κB, epithelial cell signaling in H. pylori infections, and Th17 cell differentiation. They aid in regulating the transmembrane receptor protein tyrosine kinase signaling pathway, ERBB signaling pathway, PI3K signaling pathway, and phosphorylation process. Ten key components and eight key targets, including baicalein and hederagenin, demonstrated strong binding activity.

      Conclusion

      Collectively, some core herbs exerted anti-tumor effects through immune and inflammatory pathway modulation, inhibition of immune escape, and induction of cell apoptosis. These findings support future evidence-based research on malignant lymphoma treatment using TCM.

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