: Being on the top list of neglected tropical diseases, leishmaniasis has been marked for elimination by 2020. In the light of small armamentarium of drugs and their associated drawbacks, the understanding of pharmacodynamics and/or pharmacokinetics becomes a priority to achieve and sustain disease elimination. : The authors have looked into pharmacological aspects of existing and emerging drugs for treatment of leishmaniasis. An in-depth understanding of pharmacodynamics and pharmacokinetics (PKPD) provides a rationale for drug designing and optimizing the treatment strategies. It forms a key to prevent drug resistance and avoid drug-associated adverse effects. The authors have compiled the researches on the PKPD of different anti-leishmanial formulations that have the potential for improved and/or effective disease intervention. : Understanding the pharmacological aspects of drugs forms the basis for the clinical application of novel drugs. Tailoring drug dosage and individualized treatment can avoid the adverse events and bridge gap between the models and their clinical application. An integrated approach, with pragmatic use of technological advances can improve phenotypic screening and physiochemical properties of novel drugs. Concomitantly, this can serve to improve clinical efficacies, reduce the incidence of relapse and accelerate the drug discovery/development process for leishmaniasis elimination.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6640127 | PMC |
http://dx.doi.org/10.1080/17425255.2019.1629417 | DOI Listing |
Pharmacol Ther
January 2025
School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China; School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China.
G protein-coupled receptors (GPCRs) can transmit signals via G protein-dependent or independent pathways due to the conformational changes of receptors and ligands, which is called biased signaling. This concept posits that ligands can selectively activate a specific signaling pathway after receptor activation, facilitating downstream signaling along a preferred pathway. Biased agonism enables the development of ligands that prioritize therapeutic signaling pathways while mitigating on-target undesired effects.
View Article and Find Full Text PDFLancet Neurol
February 2025
Department of Clinical Neurological Sciences, University of Western Ontario, London, ON, Canada; Department of Cognitive Neurology, St Joseph's Health Care London, London, ON, Canada. Electronic address:
Background: No treatments exist for apathy in people with frontotemporal dementia. Previously, in a randomised double-blind, placebo-controlled, dose-finding study, intranasal oxytocin administration in people with frontotemporal dementia improved apathy ratings on the Neuropsychiatric Inventory over 1 week and, in a randomised, double-blind, placebo-controlled, crossover study, a single dose of 72 IU oxytocin increased blood-oxygen-level-dependent signal in limbic brain regions. We aimed to determine whether longer treatment with oxytocin improves apathy in people with frontotemporal dementia.
View Article and Find Full Text PDFMol Divers
January 2025
Key Laboratory for Macromolecular Science of Shaanxi Province, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an, 710119, People's Republic of China.
Molecular Property Prediction (MPP) is a fundamental task in important research fields such as chemistry, materials, biology, and medicine, where traditional computational chemistry methods based on quantum mechanics often consume substantial time and computing power. In recent years, machine learning has been increasingly used in computational chemistry, in which graph neural networks have shown good performance in molecular property prediction tasks, but they have some limitations in terms of generalizability, interpretability, and certainty. In order to address the above challenges, a Multiscale Molecular Structural Neural Network (MMSNet) is proposed in this paper, which obtains rich multiscale molecular representations through the information fusion between bonded and non-bonded "message passing" structures at the atomic scale and spatial feature information "encoder-decoder" structures at the molecular scale; a multi-level attention mechanism is introduced on the basis of theoretical analysis of molecular mechanics in order to enhance the model's interpretability; the prediction results of MMSNet are used as label values and clustered in the molecular library by the K-NN (K-Nearest Neighbors) algorithm to reverse match the spatial structure of the molecules, and the certainty of the model is quantified by comparing virtual screening results across different K-values.
View Article and Find Full Text PDFExpert Opin Drug Discov
January 2025
Division of Genetics and Genomics, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA.
Introduction: Kabuki Syndrome (KS) is a rare genetic disorder characterized by distinctive facial features, intellectual disability, and multiple congenital anomalies. It is caused by pathogenic variants in the and genes. Despite its significant disease burden, there are currently no approved therapies for KS, highlighting the need for advanced research and therapeutic development.
View Article and Find Full Text PDFFront Biosci (Landmark Ed)
January 2025
Department of Hepatobiliary and Pancreatic Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, 030032 Taiyuan, Shanxi, China.
Since the discovery of the Musashi (MSI) protein, its ability to affect the mitosis of Drosophila progenitor cells has garnered significant interest among scientists. In the following 20 years, it has lived up to expectations. A substantial body of evidence has demonstrated that it is closely related to the development, metastasis, migration, and drug resistance of malignant tumors.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!