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1.
Eur J Pharmacol ; 971: 176540, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38552938

RESUMO

Identification of concomitant miRNAs and transcription factors (TFs) with differential expression (DEGs) in MI is crucial for understanding holistic gene regulation, identifying key regulators, and precision in biomarker and therapeutic target discovery. We performed a comprehensive analysis using Affymetrix microarray data, advanced bioinformatic tools, and experimental validation to explore potential biomarkers associated with human pathology. The search strategy includes the identification of the GSE83500 dataset, comprising gene expression profiles from aortic wall punch biopsies of MI and non-MI patients, which were used in the present study. The analysis identified nine distinct genes exhibiting DEGs within the realm of MI. miRNA-gene/TF and TF-gene/miRNA regulatory relations were mapped to retrieve interacting hub genes to acquire an MI miRNA-TF co-regulatory network. Furthermore, an animal model of I/R-induced MI confirmed the involved gene based on quantitative RT-PCR and Western blot analysis. The consequences of the bioinformatic tool substantiate the inference regarding the presence of three key hub genes (UBE2N, TMEM106B, and CXADR), a central miRNA (hsa-miR-124-3p), and sixteen TFs. Animal studies support the involvement of predicted genes in the I/R-induced myocardial infarction assessed by RT-PCR and Western blotting. Thus, the final consequences suggest the involvement of promising molecular pathways regulated by TF (p53/NF-κB1), miRNA (hsa-miR-124-3p), and hub gene (UBE2N), which may play a key role in the pathogenesis of MI.


Assuntos
MicroRNAs , Infarto do Miocárdio , Animais , Humanos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Redes Reguladoras de Genes , Perfilação da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , Infarto do Miocárdio/metabolismo , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética
2.
Biochem Biophys Res Commun ; 705: 149756, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38460440

RESUMO

Exacerbated expression of TLR4 protein (foremost pattern recognition receptor) during obesity could trigger NF-κB/iNOS signaling through linker protein (MyD88), predisposed to an indispensable inflammatory response. The induction of this detrimental cascade leads to myocardial and vascular abnormalities. Molecular docking was studied for protein-ligand interaction between these potential targets and resveratrol. The pre-treatment of resveratrol (20 mg/kg/p.o/per day for ten weeks) was given to investigate the therapeutic effect against HFD-induced obesity and associated vascular endothelial dysfunction (VED) and myocardial infarction (MI) in Wistar rats. In addition to accessing the levels of serum biomarkers for VED and MI, oxidative stress, inflammatory cytokines, and histopathology of these tissues were investigated. Lipopolysaccharide (for receptor activation) and protein expression analysis were introduced to explore the mechanistic involvement of TLR4/MyD88/NF-κB/iNOS signaling. Assessment of in-silico analysis showed significant interaction between protein and ligand. The involvement of this proposed signaling (TLR4/MyD88/NF-κB/iNOS) was further endorsed by the impact of lipopolysaccharide and protein expression analysis in obese and treated rats. Moreover, resveratrol pre-treated rats showed significantly lowered cardio and vascular damage measured by the distinct down expression of the TLR4/MyD88/NF-κB/iNOS pathway by resveratrol treatment endorses its ameliorative effect against VED and MI.


Assuntos
Infarto do Miocárdio , Estilbenos , Ratos , Animais , NF-kappa B/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Receptor 4 Toll-Like/metabolismo , Resveratrol/farmacologia , Estilbenos/farmacologia , Estilbenos/uso terapêutico , Lipopolissacarídeos/farmacologia , Ligantes , Simulação de Acoplamento Molecular , Ratos Wistar , Infarto do Miocárdio/tratamento farmacológico , Dieta
3.
Drug Discov Today ; 28(12): 103824, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37949428

RESUMO

Dysbiosis-associated molecular pathology is significantly involved in developing and perpetuating metabolic disorders, disrupting host energy regulation, and triggering inflammatory signaling cascades, insulin resistance, and metabolic dysfunction. Concurrently, numerous phytoconstituents are able to interact with the gut microbiota and produce bioactive metabolites that influence host cellular pathways, inflammation, and metabolic processes. These effects include improved insulin sensitivity, lipid metabolism regulation, and suppression of chronic inflammation, highlighting the therapeutic potential of phytoconstituents against metabolic abnormalities. Understanding this symbiotic relationship and the underlying molecular cascades offers innovative strategies for tailored interventions and promising therapeutic approaches to address the growing burden of metabolic disease.


Assuntos
Microbioma Gastrointestinal , Resistência à Insulina , Doenças Metabólicas , Humanos , Inflamação/metabolismo
4.
Saudi Pharm J ; 31(9): 101713, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37559867

RESUMO

Telepharmacy is a practical part of telemedicine that refers to providing pharmaceutical services within the scope of the pharmacist's obligations while maintaining a temporal and spatial distance between patients, users of health services, and healthcare professionals. The present study was a cross-sectional study conducted among community pharmacists in Saudi Arabia between March and May 2022 to assess their knowledge, perceptions, and readiness for telepharmacy. The survey was filled out by 404 respondents. The majority of respondents were male (59.90%) and the age of more than half of them was between 30 and 39 years old (54.46%). Most participants worked in urban areas (83.66%), and 42.57% had less than five years of experience in a pharmacy. Most participants agreed that telepharmacy is available in Saudi Arabia (82.67%). Approximately 70% of pharmacists felt that telepharmacy promotes patient medication adherence, and 77.72% agreed that telepharmacy increases patient access to pharmaceuticals in rural areas. More than 72% of pharmacists said they would work on telepharmacy initiatives in rural areas for free, and 74.26% said they would work outside of usual working hours if necessary. In the future, this research could aid in adopting full-fledged telepharmacy pharmaceutical care services in Saudi Arabia. It could also help academic initiatives by allowing telepharmacy practice models to be included as a topic course in the curriculum to prepare future pharmacists to deliver telepharmacy services.

5.
Healthcare (Basel) ; 11(13)2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37444807

RESUMO

Acute coronary syndrome (ACS) is a leading cause of cardiovascular-related morbidity and mortality worldwide. The present study investigated the health-related quality of life (HRQOL) and drug prescribing patterns in ACS patients at Riyadh hospitals in Saudi Arabia. This study was a 12-month prospective cross-sectional study that included 356 patients with ACS. The current study showed that younger male (67.42%) and urban (75.84%) patients suffered more from ACS. Moreover, most patients with NSTEMI (51.69%) experienced Grade 1 dyspnea (33.43%) and NYHA Stage 2 (29.80%); however, STEMI patients were at greater mortality risk. The HRQOL questionnaire showed that ACS patients were significantly impaired in all QOL domains (emotional [23.0%, p = 0.001], physical [24.4%, p = 0.003], and social [27.2%, p = 0.002]). Furthermore, the most commonly prescribed medications were statins (93%), antiplatelets (84%), anticoagulants (79%), coronary vasodilators (65%), and beta-blockers (63%). Additionally, 64% of patients received PCIs or CABGs, with the majority of cases receiving PCIs (49%), whereas 9% received dual anticoagulant therapy. Thus, there is an urgent need to educate healthcare teams about the relevance of QOL in ACS control and prevention and the new ACS management recommendations. ACS is also growing among younger people, requiring greater attention and prevention.

6.
Saudi Pharm J ; 31(4): 569-577, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37063442

RESUMO

Introduction: Medication errors (MEs) are a huge burden on any healthcare system and have been associated with significant morbidity and mortality. The medical literature reported heavily on MEs but lacked focus on analyzing high-risk medications such as antimicrobials. Research design and methods: This was a retrospective analysis of the MEs database reported by the eastern region's medical centers in Saudi Arabia from January 1, 2019 to December 31, 2019. We used descriptive analysis to identify most common antimicrobials with errors, the stage of antimicrobial errors, type of the errors, contributing factors to the errors, and categories of errors based on the National Coordinating Council for Medication Error Reporting and Prevention (NCC-MERP) classification of errors. Results: A total of 1422 (22.1%) antimicrobial errors were identified out of 6412 MEs. Amoxicillin/Clavulanate (18%) was the most common antimicrobial reported in the database. Most errors occurred in the prescribing phase (87.6%) and included mainly incorrect doses (32.1%) and duplicate therapy (20.5%). In addition, most errors were identified as category B (72.5%). Finally, inexperienced personnel (57.9%) was the most cited contributing factor. Conclusion: This study revealed that antimicrobial errors occur primarily during prescription and that policy gaps and inexperienced staff were contributory factors. To improve, the focus should shift to physician education, clear dosing guidelines, efficient workload management, and implementing antimicrobial stewardship programs to promote appropriate antimicrobial use.

7.
Healthcare (Basel) ; 11(8)2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-37107921

RESUMO

Telepharmacy is a technology-based service that provides promoted services such as counseling, medication administration and compounding, drug therapy monitoring, and prescription review. It is unclear whether hospital pharmacists possess the necessary knowledge, attitudes, and willingness to practice telepharmacy. The current study sought to investigate Saudi Arabian hospital pharmacists' understanding, attitudes, and level of preparedness for telepharmacy services. A total of 411 pharmacists responded to the survey. Only 43.33% of the respondents agreed that telepharmacy is available in Saudi Arabia and 36.67% of the respondents agreed that patients in rural areas can have more medication access and information via telepharmacy. Only 29.33% of pharmacists agreed that telepharmacy improves patient medication adherence, and about 34.00% of the pharmacists agreed that telepharmacy saves patients money and time by eliminating the need for them to travel to healthcare facilities. This research found that hospital pharmacists were unsure of their level of knowledge, their attitude toward telepharmacy, and their willingness to incorporate it into their future pharmacy practices. To ensure that tomorrow's pharmacists have the skills they need to provide telepharmacy services, telepharmacy practice models must be incorporated into the educational programs that prepare them.

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