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2.
Cureus ; 16(1): e51637, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38313892

RESUMEN

BACKGROUND: Coronary heart disease (CHD) is a leading cause of death globally, and psychological factors are increasingly recognized as playing a significant role in its prognosis. This study aimed to assess the public's awareness of psychological factors affecting CHD prognosis in Makkah, Saudi Arabia. METHODS: A cross-sectional online survey was conducted with 385 participants recruited randomly. The survey collected data on sociodemographic characteristics and respondents' opinions regarding the effects of negative and positive psychological factors on CHD prognosis, including differences based on age and gender. RESULTS: The majority of participants (96.9%) agreed that negative psychological factors, such as stress (80.5%), anxiety (76.9%), and depression (67.5%), influence CHD prognosis. Positive factors like satisfaction (79.2%) and happiness (75.6%) were also recognized as influential. Participants aged 30-50 and over 50 demonstrated higher awareness of the link between psychological factors and CHD compared to those under 30. No significant gender differences were observed in knowledge levels. CONCLUSION: This study suggests that the Makkah population has a good understanding of the impact of psychological factors on CHD prognosis. Integrating this knowledge into comprehensive health education programs could benefit CHD prevention, management, and prognosis in the region. Future research should explore broader populations and utilize diverse methodologies to refine and generalize these findings.

3.
FASEB J ; 37(8): e23075, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37432648

RESUMEN

Stimulus-coupled insulin secretion from the pancreatic islet ß-cells involves the fusion of insulin granules to the plasma membrane (PM) via SNARE complex formation-a cellular process key for maintaining whole-body glucose homeostasis. Less is known about the role of endogenous inhibitors of SNARE complexes in insulin secretion. We show that an insulin granule protein synaptotagmin-9 (Syt9) deletion in mice increased glucose clearance and plasma insulin levels without affecting insulin action compared to the control mice. Upon glucose stimulation, increased biphasic and static insulin secretion were observed from ex vivo islets due to Syt9 loss. Syt9 colocalizes and binds with tomosyn-1 and the PM syntaxin-1A (Stx1A); Stx1A is required for forming SNARE complexes. Syt9 knockdown reduced tomosyn-1 protein abundance via proteasomal degradation and binding of tomosyn-1 to Stx1A. Furthermore, Stx1A-SNARE complex formation was increased, implicating Syt9-tomosyn-1-Stx1A complex is inhibitory in insulin secretion. Rescuing tomosyn-1 blocked the Syt9-knockdown-mediated increases in insulin secretion. This shows that the inhibitory effects of Syt9 on insulin secretion are mediated by tomosyn-1. We report a molecular mechanism by which ß-cells modulate their secretory capacity rendering insulin granules nonfusogenic by forming the Syt9-tomosyn-1-Stx1A complex. Altogether, Syt9 loss in ß-cells decreases tomosyn-1 protein abundance, increasing the formation of Stx1A-SNARE complexes, insulin secretion, and glucose clearance. These outcomes differ from the previously published work that identified Syt9 has either a positive or no effect of Syt9 on insulin secretion. Future work using ß-cell-specific deletion of Syt9 mice is key for establishing the role of Syt9 in insulin secretion.


Asunto(s)
Glucosa , Insulina , Animales , Ratones , Secreción de Insulina , Sinaptotagminas/genética , Sintaxina 1/genética , Proteínas del Tejido Nervioso , Proteínas R-SNARE/genética
4.
Basic Clin Pharmacol Toxicol ; 133(4): 353-363, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37337931

RESUMEN

Brain-specific angiogenesis inhibitor 3 (ADGRB3/BAI3) belongs to the family of adhesion G protein-coupled receptors. It is most highly expressed in the brain where it plays a role in synaptogenesis and synapse maintenance. Genome-wide association studies have implicated ADGRB3 in disorders such as schizophrenia and epilepsy. Somatic mutations in ADGRB3 have also been identified in cancer. To better understand the in vivo physiological role of ADGRB3, we used CRISPR/Cas9 editing to generate a mouse line with a 7-base pair deletion in Adgrb3 exon 10. Western blot analysis confirmed that homozygous mutants (Adgrb3∆7/∆7 ) lack full-length ADGRB3 expression. The mutant mice were viable and reproduced in Mendelian ratios but demonstrated reduced brain and body weights and deficits in social interaction. Measurements of locomotor function, olfaction, anxiety levels and prepulse inhibition were comparable between heterozygous and homozygous mutants and wild-type littermates. Since ADGRB3 is also expressed in organs such as lung and pancreas, this new mouse model will facilitate elucidation of ADGRB3's role in non-central nervous system-related functions. Finally, since somatic mutations in ADGRB3 were identified in patients with several cancer types, these mice can be used to determine whether loss of ADGRB3 function contributes to tumour development.


Asunto(s)
Epilepsia , Neoplasias , Humanos , Ratones , Animales , Estudio de Asociación del Genoma Completo , Encéfalo/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Neoplasias/metabolismo
5.
Metabolites ; 13(6)2023 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-37367869

RESUMEN

Effective energy expenditure is critical for maintaining body weight (BW). However, underlying mechanisms contributing to increased BW remain unknown. We characterized the role of brain angiogenesis inhibitor-3 (BAI3/ADGRB3), an adhesion G-protein coupled receptor (aGPCR), in regulating BW. A CRISPR/Cas9 gene editing approach was utilized to generate a whole-body deletion of the BAI3 gene (BAI3-/-). In both BAI3-/- male and female mice, a significant reduction in BW was observed compared to BAI3+/+ control mice. Quantitative magnetic imaging analysis showed that lean and fat masses were reduced in male and female mice with BAI3 deficiency. Total activity, food intake, energy expenditure (EE), and respiratory exchange ratio (RER) were assessed in mice housed at room temperature using a Comprehensive Lab Animal Monitoring System (CLAMS). While no differences were observed in the activity between the two genotypes in male or female mice, energy expenditure was increased in both sexes with BAI3 deficiency. However, at thermoneutrality (30 °C), no differences in energy expenditure were observed between the two genotypes for either sex, suggesting a role for BAI3 in adaptive thermogenesis. Notably, in male BAI3-/- mice, food intake was reduced, and RER was increased, but these attributes remained unchanged in the female mice upon BAI3 loss. Gene expression analysis showed increased mRNA abundance of thermogenic genes Ucp1, Pgc1α, Prdm16, and Elov3 in brown adipose tissue (BAT). These outcomes suggest that adaptive thermogenesis due to enhanced BAT activity contributes to increased energy expenditure and reduced BW with BAI3 deficiency. Additionally, sex-dependent differences were observed in food intake and RER. These studies identify BAI3 as a novel regulator of BW that can be potentially targeted to improve whole-body energy expenditure.

6.
Medicina (Kaunas) ; 58(7)2022 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-35888557

RESUMEN

Background and Objectives: In both pandemic and non-pandemic situations, nonpharmaceutical public health measures may offer easy, low-cost, and effective means of reducing the spread and impact of acute respiratory infections. It is unknown whether such measures would be acceptable to the Saudi community beyond the current pandemic. Materials and Methods: A validated survey was used to test community acceptance of the measures. Respondents were asked which infection control practices they planned to maintain and which they believed should be policies for the community as a whole after the COVID-19 pandemic has subsided. Results: The survey was completed by 2057 people (95% completion rate), 1486 (72%) of whom were female, 259 (12.5%) of whom were current smokers, and 72 (3.5%) of whom had chronic lung disease. The most prevalent age groups were 18−30 years (933; 45.4%) and 31−40 years (483; 23.5%), with 641 individuals over 40 years old. Of the responses, 93% indicated that they would continue washing their hands more often; 92% wanted both clinicians and patients to wear masks in hospitals; 86% would continue avoiding smoking in indoor and outdoor areas; 73% would continue wearing a face covering on public transportation; 70% indicated that they would continue wearing a face covering in indoor public places. Regarding the respiratory virus infection control measures, 85% (11/13) received significant support (≥70% acceptability level) for continuation as policies in the future. Wearing face coverings outdoors and social distancing outdoors received little support (45% and 66%, respectively). Of the respiratory virus infection control measures, 54% received less support from current smokers than non-smokers (acceptability level < 70%). People with chronic respiratory disease supported 77% of the measures being regarded as policies in the future. Conclusion: The Saudi community supports nonpharmacological respiratory infection control measures that reduce the likelihood of infection. Public health campaigns should target smokers to increase awareness of the importance of these measures in lowering infections. Based on the findings of this study, nonpharmacological treatments should be presented and included in future recommendations for both the public and patients diagnosed with chronic respiratory diseases.


Asunto(s)
COVID-19 , Infecciones del Sistema Respiratorio , Adolescente , Adulto , COVID-19/prevención & control , Femenino , Humanos , Control de Infecciones , Masculino , Pandemias/prevención & control , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/prevención & control , SARS-CoV-2 , Adulto Joven
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