RESUMEN
Introduction: Osteoporosis is a prevalent challenge in clinical orthopedics, affecting a significant percentage of individuals aged 50 and above. The goal of this study was to comprehensively understand the relationships between a specialized dietary regimen and the risk of developing osteoporosis. Methods: This study employed extensive genome-wide association study (GWAS) summary statistics derived from the UK Biobank. It encompassed 8 kinds of special diets and 7 datasets pertaining to osteoporosis and associated symptoms. The principal analytical approach employed was the inverse-variance weighted method. Additionally, sensitivity analysis was employed to elucidate the diverse multiplicity patterns observed in the final model. Results: Our results showed that there is significant evidence that a gluten-free diet is associated with osteoporosis [odds ratio (OR): 1.080, 95% confidence interval (CI): 1.048-1.112, p = 4.23E-07)]. Furthermore, there exists a suggestive link between the three distinct dietary approaches and osteoporosis [(OR: 0.949, 95%CI: 0.929-0.970, p = 3.00E-06) for comprehensive consumption; (OR: 1.053, 95%CI: 1.018-1.089, p = 2.23E-03) for abstaining from wheat consumption; (OR: 1.036, 95%CI: 1.005-1.068, p = 1.97E-02) for abstaining from sugar consumption]. No additional correlation between the special dietary regimens and osteoporosis has been observed. Conclusion: Our research has uncovered a notable correlation between a gluten-free diet and the occurrence of osteoporosis. Furthermore, it exerts a promoting influence on the onset of osteoporosis, which stands in direct contradiction to the therapeutic principles for Celiac Disease's complications. As such, a novel association among these three elements is postulated.
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Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Osteoporosis , Humanos , Osteoporosis/epidemiología , Reino Unido/epidemiología , Incidencia , Femenino , Masculino , Persona de Mediana Edad , Dieta Sin Gluten/estadística & datos numéricos , Factores de Riesgo , Anciano , Dieta/estadística & datos numéricosRESUMEN
Sarcopenia, as an increasingly pressing clinical issue, can be ameliorated through employment of traditional Chinese medicines. However, the current lack of specific pharmacological interventions for Sarcopenia necessitates further exploration of novel possibilities in traditional Chinese medicine for the treatment of this condition, utilizing advanced methodologies such as web pharmacology and data mining. Screening the essential targets of Sarcopenia, conducting matching between target and active molecules, as well as active molecules and herbs. Employing data mining techniques to analyze the screening outcomes, and molecular docking to compare the binding activities of active molecules with target proteins. The approach of using herbs for the treatment of Sarcopenia involves 13 targets, with 414 active compounds and 367 types of herbs. Data mining reveals that the herbs used in treating Sarcopenia are primarily characterized by their bitter taste, exerting their effects through dispelling dampness and promoting blood circulation. Moreover, 2 new formulas are postulated. Furthermore, molecular docking analysis indicates that the main active components of the herbs can be observed to tightly bind with the targets. Through network pharmacology and molecular docking, our findings reveal that herbs contain 15 key active components and 5 key targets, which correspond to 7 major herbs and 2 new formulas. Academically, these findings hold significant reference value for the development of novel drugs targeting Sarcopenia.
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Medicamentos Herbarios Chinos , Sarcopenia , Humanos , Medicina Tradicional China/métodos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/química , Farmacología en Red , Simulación del Acoplamiento Molecular , Sarcopenia/tratamiento farmacológico , Minería de DatosRESUMEN
A disintegrin and metalloproteinase 10 (ADAM10) has been demonstrated to regulate embryonic brain development by initiating Notch signaling. However, it is still unclear whether ADAM10 is required to activate the Notch signaling pathway in adult brain. To investigate the physiological role of ADAM10, we generated conditional knockout (cKO) mice lacking the Adam10 gene primarily in the cortex and hippocampus. We found that conditional disruption of ADAM10 resulted in a prominent decrease in the number of proliferating neuronal progenitor cells in the subgranular zone (SGZ), and a significant increase in the number of adult-generated postmitotic neurons in the hippocampal dentate gyrus (DG) due to premature neuronal differentiation. Moreover, the mutant mice also displayed an age-dependent reduction in the number of granule neurons in the hippocampal DG. It was further showed that the activation of Notch-1 and its downstream target genes Hes1, Hes5, Hey1, and Hey2 was impaired in ADAM10-deficient hippocampal tissues. Finally, Adam10 cKO mice had impaired learning and memory in the Morris water-maze. Thus, we provided experimental evidence to demonstrate that ADAM10 plays an essential role in the activation of Notch-1 signaling and has a remarkable effect on neuronal maintenance in adult mouse brain.
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Proteínas ADAM/genética , Proteínas ADAM/fisiología , Secretasas de la Proteína Precursora del Amiloide/genética , Secretasas de la Proteína Precursora del Amiloide/fisiología , Encéfalo/metabolismo , Regulación de la Expresión Génica , Proteínas de la Membrana/genética , Proteínas de la Membrana/fisiología , Neuronas/metabolismo , Receptor Notch1/metabolismo , Proteína ADAM10 , Animales , Diferenciación Celular/genética , Proliferación Celular , Giro Dentado/metabolismo , Eliminación de Gen , Hipocampo/metabolismo , Masculino , Aprendizaje por Laberinto , Memoria , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Neurogénesis , Transducción de Señal , Aprendizaje EspacialRESUMEN
A disintegrin and metalloproteinase 10 (ADAM10) is a major sheddase for over 30 different membrane proteins and gets involved in such physiological processes and pathogenesis as embryonic development, cell adhesion, signal transduction, immune reaction, cancer, and Alzheimer's disease. Both ADAM10 knock-out mice and the neural progenitor cell-specific ADAM10 knock-out mice having been reported so far died in the embryonic or perinatal stage, respectively, thus resulting in the failure to investigate ADAM10 function in the adult mouse brain. Through a series of tests, we have succeeded in generating and characterizing the CaMKIIα-Cre/ADAM10(loxP/loxP) mice surviving until adulthood by means of crossing ADAM10(loxP/loxP) mice with newly generated CaMKIIα-Cre transgenic mice. PCR analysis of genomic DNAs from different regions of the ADAM10 cKO mouse brain shows that the deleted ADAM10 alleles are mainly found in the cortex and hippocampus. Real-time RT-PCR findings further confirm that ADAM10 mRNAs decrease in the cortex and hippocampus by 55.7% and 60.8%, respectively. Western-blotting analysis demonstrates 63% and 84.8% loss of mature ADAM10 proteins from the cortex and hippocampus. Immunohistochemical tests show that there is significantly less ADAM10- positive staining in the cortical and hippocampal neurons but not gliocytes of ADAM10 cKO mice compared with control mice. In summary, we established the adult neuron-specific ADAM10 knock-out (cKO) mice for the first time, which prevented ADAM10(-/-) mice from the embryonic and perinatal mortality and laid a firm foundation for the further study of ADAM10 function in the brain of adult mice in vivo.
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Proteínas ADAM/genética , Secretasas de la Proteína Precursora del Amiloide/genética , Proteínas de la Membrana/genética , Ratones Noqueados , Neuronas/enzimología , Proteínas ADAM/metabolismo , Proteína ADAM10 , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Animales , Femenino , Técnicas de Inactivación de Genes , Masculino , Proteínas de la Membrana/metabolismo , Ratones , Ratones Noqueados/embriología , Ratones Noqueados/genética , Especificidad de la EspecieRESUMEN
OBJECTIVE: To ascertain whether the carrier rate is high in Quanzhou which is next to Taiwan in South of the Yangtze River. METHODS: Population analysis of three SLC25A13 mutations, i.e. 851del4, 1638-1660 dup, and IVS6+ 5G to A was carried out in 450 healthy individuals. DNA diagnostic method of 851del4 was improved by using PCR-restriction fragment length polymorphism( PCR-RFLP) with restriction enzyme HpyCH4 IV, and the results were confirmed by GeneScan method. RESULTS: Six carriers with 851del4, 3 with 1638-1660 dup and 3 with IVS6+ 5G to A was found. CONCLUSION: The high carrier rate (0.027, 12/450) obtained from testing of only three mutations indicated that there must be a certain number of patients with citrin deficiency in Quanzhou, even in Fujian. Therefore, it is important for physicians in Quanzhou, Fujian province to learn about citrin deficiency, and to diagnose and treat the patients correctly.