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PURPOSE: To investigate the safety and efficacy of catheter-based endovascular denervation (EDN) at the celiac artery and abdominal aorta around the celiac artery on glycemic control in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: With a novel catheter system, EDN was conducted at the celiac artery along with the abdominal aorta around the celiac artery in patients with T2DM whose glycosylated hemoglobin (HbA1c) level was >7.5%. The primary outcome was HbA1c level at 6 months. Other outcomes included safety, oral glucose tolerance test, homeostasis model assessment of insulin resistance (HOMA-IR), fasting plasma glucose (FPG) level, 2-hour postprandial plasma glucose (2hPG) level, and C-peptide test. RESULTS: A total of 11 subjects were included for analysis. The technical success was 100%, and no severe treatment-related adverse events or major complications were observed. Both HbA1c level and HOMA-IR were significantly reduced at 6 months (9.9% vs 8.0%, P = .005; 13.3 vs 6.0, P = .016). Decreases in FPG and 2hPG levels were observed (227.2 vs 181.8 mg/dL, P < .001; 322.2 vs 205.2 mg/dL, P = .001). The C-peptide test indicated improved ß-cell function (area under the curve, 0.23 vs 0.28 pmol/mL, P = .046). A reduction of daily insulin injection (P = .02) and improvement of liver function (alanine aminotransferase, P = .014; γ-glutamyl transpeptidase, P = .021) were also observed. CONCLUSIONS: EDN in the celiac artery and abdominal aorta around the celiac artery elicited a clinically significant improvement in glycemic control and insulin resistance in patients with T2DM, with good tolerability as demonstrated by 6-month follow-up.
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Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Glucemia , Desnervación , Hemoglobina Glucada , Control Glucémico , Humanos , InsulinaRESUMEN
OBJECTIVE: The underlying interactions between ABO blood group antigens and pancreatic exocrine tissue have been demonstrated, and serum amylase was synthesized by pancreatic ductal cells. Thus, we investigated the link between ABO blood type and serum amylase activity in Chinese subjects. METHODS: Our study included 343 relatively healthy Chinese individuals, and the data were retrieved from electronic medical record database. RESULTS: A increased trend was observed for serum amylase activity in ABO blood type distribution, and we found that serum amylase activity was remarkable increased in subjects with O blood type compared to those with non-O blood type (P = 0.013). Logistic regression analysis indicated that serum amylase was independently associated with individuals with O blood group (adjusted odds ratio 1.574; 95% CI, 1.022-2.425, P = 0.039). CONCLUSIONS: The present evidence suggests a significant link between serum amylase activity and ABO blood type in the study population, indicating ABO blood type may be associated with the susceptibility of pancreatic disease.
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Sistema del Grupo Sanguíneo ABO/metabolismo , Amilasas/sangre , Adolescente , Adulto , Pueblo Asiatico , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , alfa-Amilasas Pancreáticas/sangre , Estudios RetrospectivosAsunto(s)
Betacoronavirus/inmunología , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/diagnóstico , Inmunidad Humoral/fisiología , Inmunoglobulina A/sangre , Neumonía Viral/sangre , Neumonía Viral/diagnóstico , Adulto , Anciano , COVID-19 , Prueba de COVID-19 , Estudios de Cohortes , Infecciones por Coronavirus/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/inmunología , SARS-CoV-2RESUMEN
The rising prevalence of metabolic disorders such as obesity and type 2 diabetes mellitus (T2DM) poses a major challenge to global health. Existing therapeutic approaches have limitations, and there is a need for new, safe, and less invasive treatments. Interventional metabolic therapy is a new addition to the treatment arsenal for metabolic disorders. This review focuses on two interventional techniques: bariatric arterial embolization (BAE) and endovascular denervation (EDN). BAE involves embolizing specific arteries feeding ghrelin-producing cells to suppress appetite and promote weight loss. EDN targets nerves that regulate metabolic organs to improve glycemic control in T2DM patients. We describe the current state of these techniques, their mechanisms of action, and the available safety and effectiveness data. We also propose a new territory called "Interventional Metabology" to encompass these and other interventional approaches to treating metabolic disorders.
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Cirugía Bariátrica , Bariatria , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/terapia , Obesidad/metabolismo , Pérdida de Peso , DesnervaciónRESUMEN
BACKGROUND AND AIM: Pancreatic fibrosis increases pancreatic cancer risk in chronic pancreatitis (CP). Pancreatic stellate cells (PSCs) play a critical role in pancreatic fibrosis by transforming growth factor-ß (TGFß) has been shown to inhibit transforming growth factor-ß receptor (TGFßR)-mediated Smad and no-Smad signaling pathways. Thus, the effects of Hsp90 inhibitor on pancreatic fibrosis are evaluated in CP mice, and the association between Hsp90 and biological functions of PSCs is further investigated in vitro. METHODS: The effects of Hsp90 inhibitor 17AAG on pancreatic fibrosis were assessed in caerulein-induced CP mice, and primary PSCs were used to determine the role of Hsp90 inhibitor 17AAG in vitro. RESULTS: We observed increased expression of Hsp90 in pancreatic tissues of caerulein-induced CP mice. Hsp90 inhibitor 17AAG ameliorated pancreatic inflammation and fibrosis in caerulein-induced CP mice. In vitro, Hsp90 inhibitor 17AAG inhibited TGFß1-induced activation and extracellular matrix accumulation of PSCs by blocking TGFßR-mediated Smad2/3 and PI3K /Akt/GSK-3ß signaling pathways.Hsp90 inhibitor 17AAG degraded TGFßRII by a ubiquitin-proteasome pathway, co-immunoprecipitation showed an interaction between Hsp90 and TGFßRII in PSCs. CONCLUSIONS: The study suggests that an Hsp90 inhibitor 17AAG remarkable prevents the development of pancreatic fibrosis in caerulein-induced CP mice, and suppresses activation and extracellular matrix accumulation of PSCs in vitro. The current results provide a potential treatment strategy based on Hsp90 inhibition for pancreatic fibrosis in CP.
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Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Pancreatitis , Receptores de Factores de Crecimiento Transformadores beta , Animales , Fibrosis , Proteínas HSP90 de Choque Térmico/metabolismo , Ratones , Páncreas/metabolismo , Pancreatitis/tratamiento farmacológico , Pancreatitis/metabolismo , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
BACKGROUND: The changes of intestinal microbiome are associated with inflammatory, metabolic, and malignant disorders, and there are no studies assessing the intestinal microbiota of mice with chronic pancreatitis (CP). Thus, we aim to investigate the variations in diversity, composition and function of intestinal microbiota in CP mice. METHODS: Sixteen male C57BL/6 mice were randomly selected, and divided into two groups, treated intraperitoneally with saline (normal control group, CT group) or ethanol + cerulein (experimental group, CP group) for 6 weeks. Body weight as measured in entire processes. Histopathological examination of CP index was conducted to verify the CP induction. Extracted DNA from colon samples was used for Illumina HiSeq sequencing of the bacterial V4 region of 16S rRNA gene and analyzed using Quantitative Insights Into Microbial Ecology (QIIME). Functional profiling of microbial communities was predicted with BugBase. RESULTS: Significant alterations of the gut microbiota were found in the CP mice compared to CT groups, as revealed by significant decrease in bacterial richness and diversity, declined the relative abundance of Lachnospiraceae_NK4A136, Ruminiclostridium and Roseburia, and increased the relative abundances of Bacteroides and Alloprevotella genera. Analysis of microbial community-level phenotypes revealed significant differences in nine phenotypes (aerobic, anaerobic, containing mobile elements, facultatively anaerobic, biofilm forming, gram-negative, gram-positive, potentially pathogenic, and stress tolerant) between CP group and CT group. CONCLUSIONS: This study indicated that mice with CP had a distinct microbiota profile.
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The homeostatic balance of hepatic glucose uptake and production is exquisitely controlled by hormonal signals during feed-fast cycles. FoxO1, a transcription factor that functions in the regulation of glucose homeostasis, undergoes posttranslational modifications, such as acetylation, in response to hormonal signals, yet the mechanism remains poorly elucidated. Through expression profiling of 324 co-factors of CBP, a well-known acetyl-transferase of FoxO1, we identify Ets1 as a modulator of FoxO1 acetylation that is highly associated with feed-fast cycles. Mechanistic assays suggest that Ets1 enhances FoxO1 acetylation through the formation of a complex with CBP, which further promotes FoxO1 nuclear exclusion and inhibits its binding to gluconeogenic promoters. Functional studies further reveal that Ets1 inhibits gluconeogenesis under physiological and diabetes statuses, while the hyperinsulinemic-euglycemic clamp assay suggests hepatocyte Ets1 knockout mice have enhanced hepatic glucose production. Our study identifies Ets1 as an enhancer of FoxO1 acetylation and a repressor of hepatic gluconeogenesis in response to hormonal signals.
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Proteína Forkhead Box O1/metabolismo , Gluconeogénesis , Hígado/metabolismo , Proteína Proto-Oncogénica c-ets-1/metabolismo , Acetilación , Animales , Células Cultivadas , Células HEK293 , Humanos , Sistema de Señalización de MAP Quinasas , Masculino , Ratones , Ratones Endogámicos C57BL , Unión Proteica , Procesamiento Proteico-Postraduccional , Proteína Proto-Oncogénica c-ets-1/genéticaRESUMEN
OBJECTIVE: Studies investigating the impact of chocolate consumption on cardiovascular disease (CVD) have reached inconsistent conclusions. As such, a quantitative assessment of the dose-response association between chocolate consumption and incident CVD has not been reported. We performed a systematic review and meta-analysis of studies assessing the risk of CVD with chocolate consumption. METHODS: PubMed and EMBASE databases were searched for articles published up to 6 June 2018. Restricted cubic splines were used to model the dose-response association. RESULTS: Fourteen publications (23 studies including 405 304 participants and 35 093 cases of CVD) were included in the meta-analysis. The summary of relative risk (RR) per 20 g/week increase in chocolate consumption was 0.982 (95% CI 0.972 to 0.992, I2=50.4%, n=18) for CVD (heart failure: 0.995 (0.981 to 1.010, I2=36.3%, n=5); total stroke: 0.956 (0.932 to 0.980, I2=25.5%, n=7); cerebral infarction: 0.952 (0.917 to 0.988, I2=0.0%, n=4); haemorrhagic stroke: 0.931 (0.871 to 0.994, I2=0.0%, n=4); myocardial infarction: 0.981 (0.964 to 0.997, I2=0.0%, n=3); coronary heart disease: 0.986 (0.973 to 0.999, n=1)). A non-linear dose-response (pnon-linearity=0.001) indicated that the most appropriate dose of chocolate consumption for reducing risk of CVD was 45 g/week (RR 0.890;95%CI 0.849 to 0.932). CONCLUSIONS: Chocolate consumption may be associated with reduced risk of CVD at <100 g/week consumption. Higher levels may negate the health benefits and induce adverse effects associated with high sugar consumption.
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Enfermedades Cardiovasculares/epidemiología , Chocolate , Ingestión de Alimentos/fisiología , Humanos , Medición de RiesgoRESUMEN
PREMISE OF THE STUDY: To quantify the population-level genetic characteristics of Cunninghamia lanceolata (Taxodiaceae), an important timber conifer, we developed 30 pairs of microsatellite primers based on the nuclear genome. METHODS AND RESULTS: Using the streptavidin-biotin capture system, we developed 14 polymorphic and 16 monomorphic microsatellites. Polymorphisms were detected in 14 loci using 94 individual trees that were collected from three C. lanceolata populations in Hubei and Zhejiang provinces and in Chongqing Municipality, China. There were three to 30 alleles per locus, and the observed and expected heterozygosities ranged from 0.0313-0.8333 and from 0.0313-0.9246, respectively. Cross-species amplification showed that two to seven polymorphic loci were functional in three of the five related species that were collected. CONCLUSIONS: Our newly developed microsatellite primers provide neutral molecular markers that are beneficial to future studies of population genetics and germplasm conservation of C. lanceolata.
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PREMISE OF THE STUDY: To estimate the genetic variation of Rhododendron ovatum (Ericaceae), a monoecious evergreen shrub, 23 microsatellite markers were identified from its nuclear genome. METHODS AND RESULTS: We developed 16 polymorphic and seven monomorphic microsatellite primers using the biotin-streptavidin capture method. The 16 polymorphic loci were investigated further using 89 individuals sampled from three populations in China. The number of alleles per locus ranged from four to 30, indicating a high level of polymorphism. The observed heterozygosity varied from 0.1034 to 0.9333, while the expected heterozygosity ranged from 0.1016 to 0.9542. Of these polymorphic primers, 12 were found to be functional in R. simsii, a congeneric species of R. ovatum. CONCLUSIONS: Moderate to high levels of genetic variation were found in these microsatellite loci, indicating that they can be applied in future studies of Rhododendron genetic structure, contributing to forest management and conservation.