RESUMEN
Parkinson's disease (PD) is a disease that involves brain damage and is associated with neuroinflammation, mitochondrial damage, and cell aging. However, the pathogenic mechanism of PD is still unknown. Sequencing data and proteomic data can describe the fluctuation of molecular abundance in diseases at the mRNA level and protein level, respectively. In order to explore new targets in the pathogenesis of PD, the study analyzed molecular changes from the database by combining transcriptomic and proteomic analysis. Differentially expressed genes and differentially abundant proteins were summarized and analyzed. Enrichment and cluster analysis emphasized the importance of neurotransmitter release, mitochondrial damage, and vesicle transport. The molecular network revealed a subnetwork of 9 molecules related to SCNA and TH and revealed hub gene with differential expression at both mRNA and protein levels. It found that ACHE and CADPS could be used as new targets in PD, emphasizing that impaired nerve signal transmission and vesicle transport affect the pathogenesis of PD. Our research emphasized that the joint analysis and verification of transcriptomics and proteomics were devoted to understanding the comprehensive views and mechanism of pathogenesis in PD.
Asunto(s)
Enfermedad de Parkinson/genética , Enfermedad de Parkinson/metabolismo , Proteínas/genética , Proteínas/metabolismo , Sustancia Negra/metabolismo , Acetilcolinesterasa/genética , Acetilcolinesterasa/metabolismo , Proteínas de Unión al Calcio/genética , Proteínas de Unión al Calcio/metabolismo , Análisis por Conglomerados , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/metabolismo , Humanos , Enfermedad de Parkinson/patología , ARN Mensajero/genética , Sustancia Negra/patología , Transcriptoma , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismoRESUMEN
AIM: To explore the correlation between serum vitamin B12 level and peripheral neuropathy in patients with chronic atrophic gastritis (CAG). METHODS: A total of 593 patients diagnosed with chronic gastritis by gastroscopy and pathological examination from September 2013 to September 2016 were selected for this study. The age of these patients ranged within 18- to 75-years-old. Blood pressure, height and weight were measured in each patient, and the body mass index value was calculated. Furthermore, gastric acid, serum gastrin, serum vitamin and serum creatinine tests were performed, and peripheral nerve conduction velocity and Helicobacter pylori (H. pylori) were detected. In addition, the type of gastritis was determined by gastroscopy. The above factors were used as independent variables to analyze chronic gastritis with peripheral neuropathy and vitamin B12 deficiency risk factors, and to analyze the relationship between vitamin B12 levels and peripheral nerve conduction velocity. In addition, in the treatment of CAG on the basis of vitamin B12, patients with peripheral neuropathy were observed. RESULTS: Age, H. pylori infection, CAG, vitamin B9 and vitamin B12 were risk factors for the occurrence of peripheral nerve degeneration. Furthermore, CAG and H. pylori infection were risk factors for chronic gastritis associated with vitamin B12 deficiency. Serum vitamin B12 level was positively correlated with sensory nerve conduction velocity in the tibial nerve (R = 0.463). After vitamin B12 supplementation, patients with peripheral neuropathy improved. CONCLUSION: Serum vitamin B12 levels in patients with chronic gastritis significantly decreased, and the occurrence of peripheral neuropathy had a certain correlation. CAG and H. pylori infection are risk factors for vitamin B12 deficiency and peripheral neuropathy. When treating CAG, vitamin B12 supplementation can significantly reduce peripheral nervous system lesions. Therefore, the occurrence of peripheral neuropathy associated with vitamin B12 deficiency may be considered in patients with CAG. Furthermore, the timely supplementation of vitamin B12 during the clinical treatment of CAG can reduce or prevent peripheral nervous system lesions.
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Gastritis Atrófica/sangre , Infecciones por Helicobacter/sangre , Helicobacter pylori/aislamiento & purificación , Enfermedades del Sistema Nervioso Periférico/epidemiología , Deficiencia de Vitamina B 12/epidemiología , Vitamina B 12/sangre , Adulto , Anciano , China/epidemiología , Femenino , Ácido Fólico/sangre , Gastritis Atrófica/diagnóstico por imagen , Gastritis Atrófica/microbiología , Gastroscopía , Infecciones por Helicobacter/microbiología , Humanos , Masculino , Persona de Mediana Edad , Conducción Nerviosa/fisiología , Enfermedades del Sistema Nervioso Periférico/sangre , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Factores de Riesgo , Nervio Tibial/fisiopatología , Deficiencia de Vitamina B 12/sangre , Deficiencia de Vitamina B 12/diagnóstico , Deficiencia de Vitamina B 12/fisiopatología , Adulto JovenRESUMEN
AIM: To investigate the effects of nesfatin-1 on gastric function in obese rats. METHODS: The obese rat model was induced by a high-fat diet. The gastric emptying rate and gastric acid secretory capacity of the rats were determined after treatment with different drug concentrations of nesfatin-1 and administration routes. Based on this, the expression of H+/K+-ATPase was measured using RT-PCR and western blot to preliminarily explore the mechanism of gastric acid secretion changes. RESULTS: Body weight, body length, and Lee's index of the rats significantly increased in the high-fat diet-induced obese rat model. Two hours after lateral intracerebroventricular injection of nesfatin-1, the gastric emptying rate and gastric acid secretory capacity of rats decreased. Four hours after injection, both were restored to normal levels. In addition, the expression of H+/K+-ATPase decreased and moved in line with changes in gastric acid secretory capacity. This in vivo experiment revealed that intracerebroventricular injection of nesfatin-1, rather than intravenous injection, could suppress gastric function in obese rats. Moreover, its effect on the gastric emptying and gastric acid secretory capacity of rats is dose-dependent within a certain period of time. CONCLUSION: Through this research, we provide a theoretical basis for further studies on nesfatin-1, a potential anti-obesity drug.
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Fármacos Antiobesidad/administración & dosificación , Proteínas de Unión al Calcio/administración & dosificación , Proteínas de Unión al ADN/administración & dosificación , Vaciamiento Gástrico/efectos de los fármacos , Proteínas del Tejido Nervioso/administración & dosificación , Obesidad/tratamiento farmacológico , Estómago/efectos de los fármacos , Animales , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Ácido Gástrico/metabolismo , Mucosa Gástrica/metabolismo , ATPasa Intercambiadora de Hidrógeno-Potásio/genética , ATPasa Intercambiadora de Hidrógeno-Potásio/metabolismo , Inyecciones Intravenosas , Inyecciones Intraventriculares , Nucleobindinas , Obesidad/metabolismo , Obesidad/fisiopatología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Sprague-Dawley , Estómago/fisiopatología , Factores de TiempoRESUMEN
BACKGROUND: There are limited data on the effect of dual antiplatelet treatment with clopidogrel plus aspirin in patients with ischemic cerebrovascular disease and intracranial and extracranial arteriostenosis. The aim of our study was to evaluate the efficacy and safety of aspirin plus clopidogrel in the treatment of ischemic cerebrovascular disease with intracranial and extracranial arteriostenosis. METHODS: Patients with clinically evident acute cerebral infarction or transient ischemic attack combined with intracranial and extracranial arteriostenosis (greater than 50%) who were unsuitable or reluctance to perform stent implantation were enrolled in this study. We randomly assigned these patients to receive clopidogrel (75 or 50âmg) plus aspirin (100âmg) or aspirin (100âmg) once daily through 90 days, and followed them for 90 days. We examined the main endpoints including the recurrence of stroke, death from cardiovascular causes, and bleeding events. RESULTS: In all, 200 patients were recruited and followed for 90 days. Ischemic stroke occurred in 6 patients (9.1%) treated with 50âmg clopidogrel and aspirin, 6 patients (9.1%) receiving 75âmg clopidogrel and aspirin, whereas 19 patients (27.9%) in the aspirin group (aspirin alone vs copidogrel 50âmg plus aspirin; 95% confidence intervals 1.704-23.779, Pâ<â0.05; aspirin alone vs copidogrel 75âmg plus aspirin; 95% confidence intervals 1.190-13.240, Pâ<â0.05). There were more hemorrhagic events among recipients (3 patients [2.3%]) in the copidogrel plus aspirin group than aspirin recipients (0 patient [0%]), including 1 subcutaneous hemorrhage in the group of 50âmg clopidogrel and aspirin, doubling the number of nasal and gum bleeding in the group of 75âmg clopidogrel and aspirin (Pâ>â0.05). No intracranial hemorrhage and gastro-intestinal hemorrhage occurred in these 3 groups. CONCLUSION: Accordingly, 50âmg clopidogrel plus aspirin, and 75âmg clopidogrel plus aspirin were all superior to aspirin alone as stroke prevention in patients with cerebral infarction or transient ischemic attack combined with intracranial and extracranial arteriostenosis. The effect of secondary stroke prevention was similar between 50âmg clopidogrel plus aspirin and 75âmg clopidogrel plus aspirin. The therapy of 75âmg clopidogrel plus aspirin resulted in a worrisome tread in bleeding events.