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1.
Front Neurol ; 15: 1366685, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39165265

RESUMO

Background: This study presents real-world evidence on the clinical outcomes of the Alberta Complementary Health Integration Project (ABCHIP), which utilized acupuncture to address pain and mental health issues in two vulnerable populations in Alberta: youth (aged 24 and below) and elderly (aged 55 and above). Methods: Over 282 days, a total of 606 patients received 5,424 acupuncture treatments. Tailored to each patients' specific pain and mental health concerns, an individualized treatment plan was selected, following a standard treatment protocol lasting 1 to 3 months. Patients were evaluated at least twice: initially and upon completing therapy. Primary treatment outcomes were assessed using various measures, including the Brief Pain Inventory (BPI), Pittsburgh Sleep Quality Index (PSQI), Patient Health Questionnaire 9 (PHQ9), PROMIS Anxiety 8a and its pediatric form PROMIS Anxiety-Pediatric, PROMIS Short Form v1.0 Fatigue 8a and its pediatric counterpart PROMIS Pediatric Short Form v2.0 Fatigue 10a, PROMIS Short Form v1.1 Anger 5a and its version PROMIS SF v2.0 5a, and EQ-5D-5L. These measures gauged pain reduction, improved sleep quality, reduced depression, anxiety, fatigue, anger, and quality of life, respectively. Results: Analysis of data from 500 patients who received at least 6 acupuncture sessions through ABCHIP showed statistically significant improvements in clinical outcomes. Among this group, the subgroup of 235 patients who received at least 12 sessions demonstrated the most favorable treatment outcomes, including an 75.5% reduction in pain severity, a 53.1% improvement in sleep quality, a 78.4% drop in depression, a 41.1% decline in anxiety, a 43.7% decrease in fatigue, a 38.2% decrease in anger, and a 42.6% improvement in overall quality of life. Conclusion: Integrating acupuncture with usual care demonstrates promise in enhancing mental health, alleviating chronic and general pain, and improving overall quality of life. The findings suggest that integrative programs, such as ABCHIP, present an effective approach to addressing pain and mental health concerns in vulnerable populations, providing valuable insights for future healthcare interventions.

2.
ChemMedChem ; 19(13): e202300688, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38602859

RESUMO

Aspartate transcarbamoylase (ATC) is the first committed step in de novo pyrimidine biosynthesis in eukaryotes and plants. A potent transition state analog of human ATCase (PALA) has previously been assessed in clinical trials for the treatment of cancer, but was ultimately unsuccessful. Additionally, inhibition of this pathway has been proposed to be a target to suppress cell proliferation in E. coli, the malarial parasite and tuberculosis. In this manuscript we screened a 70-member library of ATC inhibitors developed against the malarial and tubercular ATCases for inhibitors of the human ATC. Four compounds showed low nanomolar inhibition (IC50 30-120 nM) in an in vitro activity assay. These compounds significantly outperform PALA, which has a triphasic inhibition response under identical conditions, in which significant activity remains at PALA concentrations above 10 µM. Evidence for a druggable allosteric pocket in human ATC is provided by both in vitro enzyme kinetic, homology modeling and in silico docking. These compounds also suppress the proliferation of U2OS osteoblastoma cells by promoting cell cycle arrest in G0/G1 phase. This report provides the first evidence for an allosteric pocket in human ATC, which greatly enhances its druggability and demonstrates the potential of this series in cancer therapy.


Assuntos
Aspartato Carbamoiltransferase , Proliferação de Células , Inibidores Enzimáticos , Osteossarcoma , Humanos , Proliferação de Células/efeitos dos fármacos , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Osteossarcoma/metabolismo , Aspartato Carbamoiltransferase/antagonistas & inibidores , Aspartato Carbamoiltransferase/metabolismo , Aspartato Carbamoiltransferase/química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/síntese química , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/síntese química , Regulação Alostérica/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga , Simulação de Acoplamento Molecular , Estrutura Molecular , Ensaios de Seleção de Medicamentos Antitumorais , Linhagem Celular Tumoral , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Neoplasias Ósseas/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo
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