The phosphoinositide 3-kinases (PI3-kinases) are a ubiquitously expressed enzyme family that, through the generation of phospholipid second messengers, play a key role in the regulation of many cellular processes. These include motility, proliferation and survival, and carbohydrate metabolism. Members of the PI3-kinase family and related kinases, their mechanism of activation and the cellular events that they influence are described in this review. As knowledge of their involvement in disease processes increases, the PI3-kinases appear to be an increasingly attractive target for drug development, particularly in the fields of cancer and other proliferative diseases, and in the treatment of inflammatory and immunological conditions. Evidence of the functional specialization of PI3-kinase isoforms suggests that selective inhibition with acceptable toxicity might be possible.
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http://dx.doi.org/10.1016/s1357-4310(00)01770-6 | DOI Listing |
PLoS Negl Trop Dis
January 2025
UQ Centre for Clinical Research, Faculty of Health, Medicine, and Behavioural Sciences, The University of Queensland, Brisbane, Queensland, Australia.
Background: Sensitive diagnostic tools that signal lymphatic filariasis (LF) transmission are needed to monitor the progress of LF elimination programs. Anti-filarial antibody (Ab) markers could be more sensitive than antigen (Ag) point-of-care tests for monitoring LF transmission in some settings. This study aimed to investigate the sensitivity of anti-filarial Abs for detecting signals of LF transmission in Samoa by i) investigating the sensitivity and specificity of Ab to identify Ag-positives; ii) estimating the average number needed to test (NNTestav) to identify LF-seropositives (seropositive for Ag and/or any Ab), and iii) compare the efficiency of the different serological indicators by target age group and sampling design.
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January 2025
Shanghai Xinhao Information Technology Co., Ltd., Shanghai, China.
Machine learning techniques and computer-aided methods are now widely used in the pre-discovery tasks of drug discovery, effectively improving the efficiency of drug development and reducing the workload and cost. In this study, we used multi-source heterogeneous network information to build a network model, learn the network topology through multiple network diffusion algorithms, and obtain compressed low-dimensional feature vectors for predicting drug-target interactions (DTIs). We applied the metropolis-hasting random walk (MHRW) algorithm to improve the performance of the random walk with restart (RWR) algorithm, forming the basis by which the self-loop probability of the current node is removed.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Biology, Swarthmore College, Swarthmore, Pennsylvania, United States of America.
Mental illnesses put a tremendous burden on afflicted individuals and society. Identification of novel drugs to treat such conditions is intrinsically challenging due to the complexity of neuropsychiatric diseases and the need for a systems-level understanding that goes beyond single molecule-target interactions. Thus far, drug discovery approaches focused on target-based in silico or in vitro high-throughput screening (HTS) have had limited success because they cannot capture pathway interactions or predict how a compound will affect the whole organism.
View Article and Find Full Text PDFPLoS One
January 2025
Laboratory of Analytical and Molecular Chemistry, Faculty of Sciences Ben M'Sik, Hassan II University of Casablanca, Casablanca, Morocco.
Cognitive dysfunction in Alzheimer's disease results from a complex interplay of various pathological processes, including the dysregulation of key enzymes such as acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and monoamine oxidase B (MAO-B). This study proposes and designs a series of novel molecules derived from 8-hydroxyquinoline (Azo-8HQ) as potential multi-target lead candidates for treating AD. An exhaustive in silico analysis was conducted, encompassing docking studies, ADMET analysis, density functional theory (DFT) studies, molecular dynamics simulations, and subsequent MM-GBSA calculations to examine the pharmacological potential of these molecules with the specific targets of interest.
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January 2025
Department of Surgical Sciences, University of Wisconsin, Madison, Wisconsin, United States of America.
Temperature regulation in dogs is significantly impaired during general anesthesia. Glabrous skin on paws may facilitate thermoregulation from this area and is a potential target for interventions attenuating hypothermia. This pilot study aimed to compare efficacy of an innovative warming device placed on the front paws (AVAcore; AVA), with no warming methods (NONE) and conventional truncal warming methods (CONV; circulating water blanket/forced air warmer) on rectal temperature and anesthetic recovery times.
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