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1.
Int. j. morphol ; 42(1): 197-204, feb. 2024. ilus, graf
Article in English | LILACS | ID: biblio-1528841

ABSTRACT

SUMMARY: Obesity-related pathophysiologies such as insulin resistance and the metabolic syndrome show a markedly increased risk for type 2 diabetes and atherosclerotic cardiovascular disease. This risk appears to be linked to alterations in adipose tissue function, leading to chronic inflammation and the dysregulation of adipocyte-derived factors. Brassica rapa have been used in traditional medicine for the treatment of several diseases, including diabetes. This study aimed to investigate the effect of nutritional stress induced by a high-fat and high-sucrose diet on the pathophysiology of visceral adipose tissue and the therapeutic effect of Brassica rapa in male Wistar rats. We subjected experimental rats to a high-fat (10 %) high-sucrose (20 %)/per day for 11 months and treated them for 20 days with aqueous extract Br (AEBr) at 200 mg/kg at the end of the experiment. At the time of sacrifice, we monitored plasma and tissue biochemical parameters as well as the morpho-histopathology of visceral adipose tissue. We found AEBr corrected metabolic parameters and inflammatory markers in homogenized visceral adipose tissue and reduced hypertrophy, hyperplasia, and lipid droplets. These results suggest that AEBr enhances anti-diabetic, anti-inflammatory and a protective effect on adipose tissue morphology in type 2 diabetes and obesity.


La fisiopatología relacionadas con la obesidad, como la resistencia a la insulina y el síndrome metabólico, muestran un riesgo notablemente mayor de diabetes tipo 2 y enfermedad cardiovascular aterosclerótica. Este riesgo parece estar relacionado con alteraciones en la función del tejido adiposo, lo que lleva a una inflamación crónica y a la desregulación de los factores derivados de los adipocitos. Brassica rapa se ha utilizado en la medicina tradicional para el tratamiento de varias enfermedades, incluida la diabetes. Este estudio tuvo como objetivo investigar el efecto del estrés nutricional inducido por una dieta rica en grasas y sacarosa sobre la fisiopatología del tejido adiposo visceral y el efecto terapéutico de Brassica rapa en ratas Wistar macho. Sometimos a ratas experimentales a una dieta rica en grasas (10 %) y alta en sacarosa (20 %)/por día durante 11 meses y las tratamos durante 20 días con extracto acuoso de Br (AEBr) a 200 mg/kg al final del experimento. En el momento del sacrificio, monitoreamos los parámetros bioquímicos plasmáticos y tisulares, así como la morfohistopatología del tejido adiposo visceral. Encontramos parámetros metabólicos corregidos por AEBr y marcadores inflamatorios en tejido adiposo visceral homogeneizado y reducción de hipertrofia, hiperplasia y gotitas de lípidos. Estos resultados sugieren que AEBr mejora el efecto antidiabético, antiinflamatorio y protector sobre la morfología del tejido adiposo en la diabetes tipo 2 y la obesidad.


Subject(s)
Animals , Male , Rats , Plant Extracts/administration & dosage , Adipose Tissue/drug effects , Brassica rapa/chemistry , Insulin Resistance , Plant Extracts/therapeutic use , Rats, Wistar , Diabetes Mellitus, Type 2/drug therapy , Intra-Abdominal Fat , Glucose/toxicity , Inflammation , Lipids/toxicity , Obesity/drug therapy
2.
Chinese Journal of Contemporary Pediatrics ; (12): 54-61, 2024.
Article in Chinese | WPRIM | ID: wpr-1009893

ABSTRACT

OBJECTIVES@#To explore the relationship of triglyceride-glucose index (TyG), triglyceride-glucose-body mass index (TyG-BMI), and triglyceride-glucose-waist circumference index (TyG-WC) with blood pressure abnormalities in adolescents, providing theoretical basis for the prevention and control of hypertension in adolescents.@*METHODS@#A stratified cluster sampling method was used to select 1 572 adolescents aged 12 to 18 years in Yinchuan City for questionnaire surveys, physical measurements, and laboratory tests. Logistic regression analysis and restricted cubic spline analysis were employed to examine the relationship of TyG, TyG-BMI, and TyG-WC with blood pressure abnormalities in adolescents.@*RESULTS@#Multivariable logistic regression analysis revealed that after adjusting for confounding factors, the groups with the highest quartile of TyG, TyG-BMI, and TyG-WC had 1.48 times (95%CI: 1.07-2.04), 3.71 times (95%CI: 2.67-5.15), and 4.07 times (95%CI: 2.89-5.73) higher risks of blood pressure abnormalities compared to the groups with the lowest quartile, respectively. Moreover, as the levels of TyG, TyG-BMI, and TyG-WC increased, the risk of blood pressure abnormalities gradually increased (P<0.05). A non-linear dose-response relationship was observed between TyG-BMI and the risk of blood pressure abnormalities (P overall trend<0.001, P non-linearity=0.002). Linear dose-response relationships were found between TyG and the risk of blood pressure abnormalities (P overall trend<0.001, P non-linearit =0.232), and between TyG-WC and the risk of blood pressure abnormalities (P overall trend<0.001, P non-linearity=0.224).@*CONCLUSIONS@#Higher levels of TyG and its derivatives are associated with an increased risk of blood pressure abnormalities in adolescents, with linear or non-linear dose-response relationships.


Subject(s)
Adolescent , Humans , Blood Pressure , Body Mass Index , Hypertension/etiology , Glucose , Triglycerides
3.
Rev. méd. Chile ; 151(1): 81-100, feb. 2023. ilus, tab
Article in Spanish | LILACS | ID: biblio-1515424

ABSTRACT

Intermittent fasting (IF) has gained increasing scientific and general attention. Most studied forms of IF include alternate-day fasting, modified alternate-day fasting, and time-restricted eating (TRE). Several cardiometabolic effects of IF have been described in animal models and, to a lesser extent, in humans. This review analyzes the impact of IF on weight loss, glucose metabolism, blood pressure, and lipid profile in humans. A literature search was conducted in the Pubmed/Medline, Scopus, and Google Scholar databases. Controlled observational or interventional studies in humans, published between January 2000 and June 2021, were included. Studies comparing IF versus religious fasting were not included. Most studies indicate that the different types of IF have significant benefits on body composition, inducing weight loss and reducing fat mass. Changes in cardiometabolic parameters show more divergent results. In general, a decrease in fasting glucose and insulin levels is observed, together with an improved lipid profile associated with cardiovascular risk. High heterogeneity in study designs was observed, particularly in studies with TRE, small sample sizes, and short-term interventions. Current evidence shows that IF confers a range of cardiometabolic benefits in humans. Weight loss, improvement of glucose homeostasis and lipid profile, are observed in the three types of IF protocols evaluated.


Subject(s)
Humans , Animals , Cardiovascular Diseases/prevention & control , Intermittent Fasting , Weight Loss , Fasting/physiology , Glucose/metabolism , Lipids
4.
Journal of Medicine University of Santo Tomas ; (2): 1310-1316, 2023.
Article in English | WPRIM | ID: wpr-998862

ABSTRACT

@#Higher dietary intake of polyphenols is associated with a reduced risk of cardiovascular disease (CVD) events and mortality. However, these phytochemicals are predominantly present in fruits and vegetables, which are inadequately consumed by some populations, including Filipinos. This narrative mini-review explores the potential role of polyphenol-containing pigmented rice consumption in modulating risk through a range of mechanisms identified in animal studies. Further, human studies have demonstrated promising but inconsistent effects on risk factors associated with the development of CVD, such as dyslipidemia, hyperglycemia, overweight and obesity. Therefore, this review identifies the need for more clinical trials to examine the effect of pigmented rice on CVD risk factors.


Subject(s)
Cholesterol , Glucose , Polyphenols
5.
Braz. j. biol ; 83: e250179, 2023. graf
Article in English | LILACS, VETINDEX | ID: biblio-1339372

ABSTRACT

Abstract Diabetes mellitus (DM) is a non-communicable disease throughout the world in which there is persistently high blood glucose level from the normal range. The diabetes and insulin resistance are mainly responsible for the morbidities and mortalities of humans in the world. This disease is mainly regulated by various enzymes and hormones among which Glycogen synthase kinase-3 (GSK-3) is a principle enzyme and insulin is the key hormone regulating it. The GSK-3, that is the key enzyme is normally showing its actions by various mechanisms that include its phosphorylation, formation of protein complexes, and other cellular distribution and thus it control and directly affects cellular morphology, its growth, mobility and apoptosis of the cell. Disturbances in the action of GSK-3 enzyme may leads to various disease conditions that include insulin resistance leading to diabetes, neurological disease like Alzheimer's disease and cancer. Fluoroquinolones are the most common class of drugs that shows dysglycemic effects via interacting with GSK-3 enzyme. Therefore, it is the need of the day to properly understand functions and mechanisms of GSK-3, especially its role in glucose homeostasis via effects on glycogen synthase.


Resumo O diabetes mellitus (DM) é uma doença não transmissível em todo o mundo, na qual existe nível glicêmico persistentemente alto em relação à normalidade. O diabetes e a resistência à insulina são os principais responsáveis ​​pelas morbidades e mortalidades de humanos no mundo. Essa doença é regulada principalmente por várias enzimas e hormônios, entre os quais a glicogênio sintase quinase-3 (GSK-3) é uma enzima principal e a insulina é o principal hormônio que a regula. A GSK-3, que é a enzima-chave, normalmente mostra suas ações por vários mecanismos que incluem sua fosforilação, formação de complexos de proteínas e outras distribuições celulares e, portanto, controla e afeta diretamente a morfologia celular, seu crescimento, mobilidade e apoptose do célula. Perturbações na ação da enzima GSK-3 podem levar a várias condições de doença que incluem resistência à insulina que leva ao diabetes, doenças neurológicas como a doença de Alzheimer e câncer. As fluoroquinolonas são a classe mais comum de drogas que apresentam efeitos disglicêmicos por meio da interação com a enzima GSK-3. Portanto, é necessário hoje em dia compreender adequadamente as funções e mecanismos da GSK-3, principalmente seu papel na homeostase da glicose via efeitos na glicogênio sintase.


Subject(s)
Humans , Insulin Resistance , Diabetes Mellitus , Glycogen Synthase Kinase 3 , Glucose , Homeostasis
6.
Arch. pediatr. Urug ; 94(2): e214, 2023. tab
Article in Spanish | LILACS, UY-BNMED, BNUY | ID: biblio-1520114

ABSTRACT

Introducción: la hipoglicemia neonatal es un trastorno metabólico frecuente en neonatos, con mayor incidencia en aquellos con factores de riesgo como ser hijos de madre diabética, pequeño para la edad gestacional y pretérmino tardíos. Material y métodos: se realizó un ensayo analítico aleatorizado, controlado por placebo para evaluar la eficacia de la administración de gel de dextrosa al 40% para la prevención de hipoglicemia neonatal en esta población. Se reclutaron un total de 120 pacientes. Resultados: se encontró una menor incidencia de hipoglicemia neonatal al compararla con la incidencia reportada en la literatura internacional. No se encontraron diferencias estadísticamente significativas en cuanto al número de ingresos a áreas de internación para tratamiento de hipoglicemia ni en la alimentación a pecho directo exclusivo al alta entre los grupos. Conclusiones: el gel de dextrosa al 40% en recién nacidos podría ser un tratamiento alternativo para profilaxis de hipoglicemia en recién nacidos con factores de riesgo.


Introduction: neonatal hypoglycemia is a frequent metabolic disorder in neonates, with a higher incidence in those with risk factors such as being children of diabetic mothers, small for gestational age, and late preterm. Methodology: a randomized, placebo controlled analytic trial was conducted to evaluate the efficacy of 40% dextrose gel administration for the prevention of neonatal hypoglycemia in this population. A total of 120 patients were recruited. Results: a lower incidence of neonatal hypoglycemia was found when compared to the incidence reported in the international literature. No statistically significant differences were found in terms of the number of admissions to inpatient areas for hypoglycemia treatment or exclusive direct breastfeeding at discharge between the groups. Conclusions: 40% dextrose gel in newborns could be an alternative treatment for hypoglycemia prophylaxis in newborns with risk factors.


Introdução: a hipoglicemia neonatal é um disturbio metabólico comum em neonatos, com maior incidencia naqueles que apresentam fatores de risco, tais como filhos de mães diabéticas, pequenos para a idade gestacional e prematuros tardios. Metodologia: foi realizado um ensaio analítico randomizado e controlado por placebo para avaliar a eficácia da administração de gel de dextrose a 40% para prevenção de hipoglicemia neonatal nesta população. Um total de 120 pacientes foram recrutados. Resultados: foi encontrada menor incidência de hipoglicemia neonatal quando comparada com a incidência relatada na literatura internacional. Não foram encontradas diferenças estatisticamente significativas relativas ao número de internações em áreas de internação para tratamento de hipoglicemia ou aleitamento materno direto exclusivo para descarga entre os grupos. Conclusões: o gel de dextrose a 40% em recém nascidos pode ser uma alternativa de tratamento para profilaxia de hipoglicemia em recém nascidos com fatores de risco.


Subject(s)
Humans , Male , Female , Infant, Newborn , Congenital Hyperinsulinism/prevention & control , Glucose/therapeutic use , Double-Blind Method , Risk Factors , Congenital Hyperinsulinism/blood
7.
Biol. Res ; 56: 5-5, 2023. ilus, graf
Article in English | LILACS | ID: biblio-1429906

ABSTRACT

BACKGROUND: Alpha-kinase 1 (ALPK1) is a master regulator in inflammation and has been proved to promote renal fibrosis by promoting the production of IL-1ß in diabetic nephropathy (DN) mice. Pyroptosis is involved in high glucose (HG)-induced tubular cells injury, characterized by activation of Gasdermin D (GSDMD) and the release of IL-1ß and IL-18, resulting in inflammatory injury in DN. It is reasonable to assume that ALPK1 is involved in pyroptosis-related tubular injury in DN. However, the mechanism remains poorly defined. METHODS: Immunohistochemistry (IHC) staining was performed to detect the expression of pyroptosis- and fibrosis-related proteins in renal sections of DN patients and DN mice. DN models were induced through injection of streptozotocin combined with a high-fat diet. Protein levels of ALPK1, NF-κB, Caspase-1, GSDMD, IL-1ß, IL-18 and α-SMA were detected by Western blot. HK-2 cells treated with high-glucose (HG) served as an in vitro model. ALPK1 small interfering RNA (siRNA) was transfected into HK-2 cells to down-regulate ALPK1. The pyroptosis rates were determined by flow cytometry. The concentrations of IL-1ß and IL-18 were evaluated by ELISA kits. Immunofluorescence staining was used to observe translocation of NF-κB and GSDMD. RESULTS: The heat map of differentially expressed genes showed that ALPK1, Caspase-1 and GSDMD were upregulated in the DN group. The expression levels of ALPK1, Caspase-1, GSDMD and CD68 were increased in renal biopsy tissues of DN patients by IHC. ALPK1expression and CD68+ macrophages were positively correlated with tubular injury in DN patients. Western blot analysis showed increased expressions of ALPK1, phospho-NF-κB P65, GSDMD-NT, and IL-1ß in renal tissues of DN mice and HK-2 cells, accompanied with increased renal fibrosis-related proteins (FN, α-SMA) and macrophages infiltration in interstitial areas. Inhibition of ALPK1 attenuated HG-induced upregulation expressions of NF-κB, pyroptosis-related proteins Caspase-1, GSDMD-NT, IL-1ß, IL-18, α-SMA, and pyroptosis level in HK-2 cells. Also, the intensity and nuclear translocation of NF-κB and membranous translocation of GSDMD were ameliorated in HG-treated HK-2 cells after treatment with ALPK1 siRNA. CONCLUSIONS: Our data suggest that ALPK1/NF-κB pathway initiated canonical caspase-1-GSDMD pyroptosis pathway, resulting in tubular injury and interstitial inflammation of DN.


Subject(s)
Animals , Mice , Diabetes Mellitus , Diabetic Nephropathies , Fibrosis , NF-kappa B/metabolism , Caspases , Interleukin-18 , RNA, Small Interfering , Pyroptosis , Glucose , Inflammation
8.
Journal of Southern Medical University ; (12): 1093-1101, 2023.
Article in Chinese | WPRIM | ID: wpr-987026

ABSTRACT

OBJECTIVE@#To investigate the effects of Naoluo Xintong Decoction (NLXTD) on pyroptosis and angiogenesis of brain microvascular endothelial cells (BMECs) and explore the possible mechanisms in rats with oxygen-glucose deprivation/ reperfusion (OGD/R).@*METHODS@#Rat BMECs with or without caspase-1 siRNA transfection were cultured in the presence of 10% medicated serum from NLXTD-treated rats (or blank serum) and exposed to OGD/R. CCK-8 assay, Transwell chamber assay, and tube formation assay were used to assess proliferation, migration, and tube-forming abilities of the cells. The activity of lactate dehydrogenase (LDH) in the culture supernatant was determined using a commercial assay kit, and the levels of inflammatory factors IL-1β and IL-18 were detected with ELISA. The cellular expressions of pro-caspase-1, caspase-1, NLRP3, Gasdermin D, and angiogenesis-related proteins VEGF and VEGFR2 were detected using Western blotting.@*RESULTS@#The BMECs showed obvious injuries after OGD/R exposure. Compared with the blank serum, the medicated serum significantly improved the cell viability, migration ability, and lumen-forming ability (P < 0.01) and lowered the levels of IL-1β and IL-18 and the LDH release (P < 0.01) of the cells with OGD/R exposure. Western blotting showed that in the BMECs exposed to OGD/R, the medicated serum strongly upregulated the expression of VEGF and VEGFR2 proteins (P < 0.01) and reduced the protein expressions of pro-caspase-1, caspase-1, NLRP3, and Gasdermin D (P < 0.01), and transfection of the cells with caspase-1 siRNA further promoted the expressions of VEGFR2 protein in the cells (P < 0.01).@*CONCLUSION@#NLXTD can improve the proliferation, migration, and tube- forming ability and promote angiogenesis of BMECs with OGD/R injury probably by inhibiting the caspase-1/Gasdermin D pathway in pyroptosis, alleviating cell injury, and upregulating the expressions of VEGF and VEGFR2.


Subject(s)
Animals , Rats , Endothelial Cells , Caspase 1 , Gasdermins , Interleukin-18 , NLR Family, Pyrin Domain-Containing 3 Protein , Vascular Endothelial Growth Factor A , Reperfusion Injury , Brain , Angiogenic Proteins , Glucose
9.
Journal of Southern Medical University ; (12): 1063-1070, 2023.
Article in Chinese | WPRIM | ID: wpr-987023

ABSTRACT

OBJECTIVE@#To investigate the prognostic value of death-associated protein 5 (DAP5) in gastric cancer (GC) and its regulatory effect on aerobic glycolysis in GC cells.@*METHODS@#We analyzed DAP5 expression levels in GC and adjacent tissues and its association with survival outcomes of GC patients using public databases. We collected paired samples of GC and adjacent tissues from 102 patients undergoing radical resection of GC in our hospital from June, 2012 to July, 2017, and analyzed the correlation of DAP5 expression level detected immunohistochemically with the clinicopathological parameters of the patients. Cox regression analysis, Kaplan-Meier analysis, and ROC curves were used to explore the independent risk factors and the predictive value of DAP5 expression for 5-year survival of the patients. In the cell experiments, we observed the changes in aerobic glycolysis in MGC-803 cells following lentivirus-mediated DAP5 knockdown or overexpression by measuring glucose uptake and cellular lactate level and using qRT-PCR and Western blotting.@*RESULTS@#Analysis using the public databases showed that DAP5 was highly expressed in GC and correlated with tumor progression and poor survival outcomes of the patients (P < 0.05). In the clinical samples, DAP5 expression was significantly higher in GC than in the adjacent tissues (3.19±0.60 vs 1.00±0.12; t=36.863, P < 0.01), and a high expression of DAP5 was associated with a reduced 5-year survival rate of the patients (17.6% vs 72.5%; χ2=29.921, P < 0.05). A high DAP5 expression, T3-4, N2-3, and CEA≥5 ng/mL were identified as independent risk factors affecting 5-year survival outcomes of GC (P < 0.05), for which DAP5 expression showed a prediction sensitivity, specificity and accuracy of 73.2%, 80.4% and 79.0%, respectively. In MGC-803 cells, DAP5 knockdown significantly reduced glucose uptake, lactate level and the expressions of GLUT1, HK2 and LDHA, and DAP5 overexpression produced the opposite effects (P < 0.05).@*CONCLUSION@#A high expression of DAP5 in GC, which enhances cellular aerobic glycolysis to promote cancer progression, is correlated with a poor survival outcome and may serve as a biomarker for evaluating long-term prognosis of GC patients.


Subject(s)
Humans , Stomach Neoplasms , Blotting, Western , Databases, Factual , Glucose , Lactates
10.
Journal of Southern Medical University ; (12): 852-858, 2023.
Article in Chinese | WPRIM | ID: wpr-986997

ABSTRACT

OBJECTIVE@#To explore the molecular pathological mechanism of liver metabolic disorder in severe spinal muscular atrophy (SMA).@*METHODS@#The transgenic mice with type Ⅰ SMA (Smn-/- SMN20tg/2tg) and littermate control mice (Smn+/- SMN20tg/2tg) were observed for milk suckling behavior and body weight changes after birth. The mice with type Ⅰ SMA mice were given an intraperitoneal injection of 20% glucose solution or saline (15 μL/12 h), and their survival time was recorded. GO enrichment analysis was performed using the RNA-Seq data of the liver of type Ⅰ SMA and littermate control mice, and the results were verified using quantitative real-time PCR. Bisulfite sequencing was performed to examine CpG island methylation level in Fasn gene promoter region in the liver of the neonatal mice.@*RESULTS@#The neonatal mice with type Ⅰ SMA showed normal milk suckling behavior but had lower body weight than the littermate control mice on the second day after birth. Intraperitoneal injection of glucose solution every 12 h significantly improved the median survival time of type Ⅰ SMA mice from 9±1.3 to 11± 1.5 days (P < 0.05). Analysis of the RNA-Seq data of the liver showed that the expression of the target genes of PPARα related to lipid metabolism and mitochondrial β oxidation were down-regulated in the liver of type Ⅰ SMA mice. Type Ⅰ SMA mice had higher methylation level of the Fasn promoter region in the liver than the littermate control mice (76.44% vs 58.67%). In primary cultures of hepatocytes from type Ⅰ SMA mice, treatment with 5-AzaC significantly up-regulated the expressions of the genes related to lipid metabolism by over 1 fold (P < 0.01).@*CONCLUSION@#Type Ⅰ SMA mice have liver metabolic disorder, and the down-regulation of the target genes of PPARα related to lipid and glucose metabolism due to persistent DNA methylation contributes to the progression of SMA.


Subject(s)
Mice , Animals , PPAR alpha , Liver Diseases , Muscular Atrophy, Spinal/genetics , Mice, Transgenic , Body Weight , Glucose
11.
Journal of Southern Medical University ; (12): 585-589, 2023.
Article in Chinese | WPRIM | ID: wpr-986965

ABSTRACT

OBJECTIVE@#Bo investigate the regulatory relationship between NKD1 and YWHAE and the mechanism of NKD1 for promoting tumor cell proliferation.@*METHODS@#HCT116 cells transfected with pcDNA3.0-NKD1 plasmid, SW620 cells transfected with NKD1 siRNA, HCT116 cells with stable NKD1 overexpression (HCT116-NKD1 cells), SW620 cells with nkd1knockout (SW620-nkd1-/- cells), and SW620-nkd1-/- cells transfected with pcDNA3.0-YWHAE plasmid were examined for changes in mRNA and protein expression levels of YWHAE using qRT-PCR and Western blotting. Chromatin immunoprecipitation (ChIP) assay was used to detect the binding of NKD1 to the promoter region of YWHAE gene. The regulatory effect of NKD1 on YWHAE gene promoter activity was analyzed by dual-luciferase reporter gene assay, and the interaction between NKD1 and YWHAE was analyzed with immunofluorescence assay. The regulatory effect of NKD1 on glucose uptake was examined in the tumor cells.@*RESULTS@#In HCT116 cells, overexpression of NKD1 significantly enhanced the expression of YWHAE at both the mRNA and protein levels, while NKD1 knockout decreased its expression in SW620 cells (P < 0.001). ChIP assay showed that NKD1 protein was capable of binding to the YWHAE promoter sequence; dual luciferase reporter gene assay showed that NKD1 overexpression (or knockdown) in the colon cancer cells significantly enhanced (or reduced) the transcriptional activity of YWHAE promoter (P < 0.05). Immunofluorescence assay demonstrated the binding of NKD1 and YWHAE proteins in colon cancer cells. NKD1 knockout significantly reduced glucose uptake in colon cancer cells (P < 0.01), while YWHAE overexpression restored the glucose uptake in NKD1-knockout cells (P < 0.05).@*CONCLUSION@#NKD1 protein activates the transcriptional activity of YWHAE gene to promote glucose uptake in colon cancer cells.


Subject(s)
Humans , Colonic Neoplasms , HCT116 Cells , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic , RNA, Messenger , Glucose , Calcium-Binding Proteins/metabolism , Adaptor Proteins, Signal Transducing/metabolism , 14-3-3 Proteins/metabolism
12.
Chinese Journal of Otorhinolaryngology Head and Neck Surgery ; (12): 681-689, 2023.
Article in Chinese | WPRIM | ID: wpr-986945

ABSTRACT

Objective: To investigate whether tanshinone ⅡA can protect the apoptosis of mice cochlear pericytes induced by high glucose and its specific protective mechanism, so as to provide experimental evidence for the prevention and treatment of diabetic hearing loss. Methods: C57BL/6J male mice were used to prepare type 2 diabetes model, which were divided into normal (NG) group, diabetic (DM) group, diabetic+tanshinone ⅡA (HG+tanshinone ⅡA) group and tanshinone ⅡA group. Each group had 10 animals. Primary cochlear pericytes were divided into NG group, HG group (high glucose 35 mmol/L), HG+tanshinone ⅡA (1, 3, 5 μmol/L) group, HG+Tanshinone ⅡA+LY294002 (PI3K/AKT pathway inhibitor) group, LY294002 group, tanshinone ⅡA group and DMSO group. Auditory brainstem response (ABR) was used to measure hearing threshold. Evans blue was used to detect the permeability of blood labyrinth barrier in each group. TBA methods were used to detect oxidative stress levels in various organs of mice. Morphological changes of stria vascularis were observed by hematoxylin-eosin staining (HE). Evans blue was used to detect the vascular labyrinth barrier permeability in cochlea. The expression of apoptosis protein in stria vascularis pericytes was observed by immunofluorescence. Pericytes apoptosis rate was observed by flow cytometry. DCFH-DA was combined with flow cytometry to detect intracellular ROS content, and Western blot was used to detect the expression of apoptotic proteins (Cleaved-caspase3, Bax), anti-apoptotic proteins (BCL-2) and pathway proteins (PI3K, p-PI3K, AKT, p-AKT). SPSS software was used for statistical analysis. Independent sample t test was performed, and P<0.05 was considered statistically significant. Results: Animal experiments: Tanshinone ⅡA decreased the hearing threshold of DM group [(35.0±3.5) dB SPL vs. (55.3±8.1) dB SPL] (t=4.899, P<0.01), decreased the oxidative stress level in cochlea (t=4.384, P<0.05), improved the structure disorder, atrophy of cochlea vascular lines, vacuole increased phenomenon. Tanshinone ⅡA alleviated the increased permeability of the blood labyrinth barrier [Evans blue leakage (6.84±0.27) AU vs. (8.59±0.85) AU] in the cochlea of DM mice (t=2.770, P<0.05), reversed the apoptotic protein: Caspase3 (t=4.956, P<0.01) and Bax (t=4.388, P<0.05) in cochlear vascularis. Cell experiments: Tanshinone ⅡA decreased intracellular ROS content in a concentration-dependent way (t=3.569, P<0.05; t=4.772, P<0.01; t=7.494, P<0.01); Tanshinone ⅡA decreased apoptosis rate and apoptotic protein, and increased the expression of anti-apoptotic protein, p-PI3K/PI3K and p-AKT/AKT in concentration-dependent manner (all P values<0.05); LY294002 reversed the protective effect of tanshinone ⅡA on pericytes apoptosis (all P values<0.05). Conclusion: Tanshinone ⅡA can inhibit the apoptosis of cochlear pericytes induced by high glucose by reducing oxidative stress level and activating PI3K/AKT signaling pathway under high glucose environment, thus playing a protective role in diabetic hearing loss.


Subject(s)
Animals , Male , Mice , Apoptosis , bcl-2-Associated X Protein , Diabetes Mellitus, Type 2 , Evans Blue , Glucose , Hearing Loss , Mice, Inbred C57BL , Pericytes/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Reactive Oxygen Species/metabolism , Signal Transduction
13.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 610-618, 2023.
Article in English | WPRIM | ID: wpr-1010974

ABSTRACT

In this study, we presented the isolation and characterization of eight novel seco-guaianolide sesquiterpenoids (1-8) and two known guaianolide derivatives (9 and 10), from the aerial part of Achillea alpina L.. Compounds 1-3 were identified as guaianolides bearing an oxygen insertion at the 2, 3 position, while compounds 4-8 belonged to a group of special 3-nor guaianolide sesquiterpenoids. The structural elucidation of 1-8, including their absolute configurations, were accomplished by a combination of spectroscopic data analysis and quantum electronic circular dichroism (ECD) calculations. To evaluate the potential antidiabetic activity of compounds 1-10, we investigated their effects on glucose consumption in palmitic acid (PA)-mediated HepG2-insulin resistance (IR) cells. Among the tested compounds, compound 7 demonstrated the most pronounced ability to reverse IR. Moreover, a mechanistic investigation revealed that compound 7 exerted its antidiabetic effect by reducing the production of the pro-inflammatory cytokine IL-1β, which was achieved through the suppression of the NLRP3 pathway.


Subject(s)
Humans , Hypoglycemic Agents/pharmacology , Circular Dichroism , Cytokines , Glucose , Hep G2 Cells , Insulin Resistance
14.
Chinese Critical Care Medicine ; (12): 1298-1303, 2023.
Article in Chinese | WPRIM | ID: wpr-1010943

ABSTRACT

OBJECTIVE@#To investigate the clinical effect of Shenfu injection combined with glucocorticoid in the treatment of acute left heart failure complicated with bronchospasm.@*METHODS@#A prospective study was conducted.Ninety patients with acute left heart failure complicated with bronchospasm admitted to Huai'an Second People's Hospital from January 2021 to July 2022 were selected and divided into conventional treatment group, hormone therapy group and combined treatment group according to random number table method, with 30 cases in each group. All patients in the 3 groups received basic Western medicine treatment. On this basis, the conventional treatment group was given 0.25-0.50 g aminophylline injection plus 5% glucose injection or 0.9% sodium chloride injection (diabetes patients) 100 mL slow intravenous infusion, 1-2 times a day. In the hormone treatment group, 1 mg of budesonide suspension for inhalation was diluted to 2 mL by 0.9% sodium chloride injection, twice a day, and applied until 48 hours after the pulmonary wheezing disappeared. The combined treatment group was given glucocorticoid combined with Shenfu injection 80 mL plus 5% glucose injection or 0.9% sodium chloride injection (diabetes patients) 250 mL intravenously, once a day. All treated for 1 week. The general data, traditional Chinese medicine (TCM) syndrome score, TCM syndrone efficacy index, acute left heart failure efficacy, bronchospasm efficacy, systolic blood pressure (SBP), mean arterial pressure (MAP), serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level and safety of the 3 groups were compared. The patients were followed up for 6 months, and the mortality and re-hospitalization rate of the 3 groups were recorded.@*RESULTS@#Among the 90 patients, a total of 83 patients completed the study, excluding the cases dropped due to death and other reasons. There were 29 cases in the combined treatment group, 25 cases in the hormone therapy group and 29 cases in the conventional treatment group. There were no significant differences in age, gender, course of disease, and previous history (history of diabetes, history of hypertension, history of hyperlipidemia) among the 3 groups. Therefore, they were comparable. The difference of TCM syndrome score before and after treatment, TCM syndrome efficacy index of combined treatment group and hormone therapy group were higher than those of conventional treatment group [difference of TCM syndrome score: 15.14±5.74, 13.24±5.75 vs. 10.62±5.87, TCM syndrome efficacy index: (67.84±14.31)%, (59.94±14.26)% vs. (48.92±16.74)%, all P < 0.05], and the difference of TCM syndrome score and TCM syndrome efficacy index of combined treatment group were higher than those of hormone treatment group (both P < 0.05). The total effective rate of acute left heart failure and bronchospasm in the combined treatment group was significantly higher than that in the conventional treatment group (total effective rate of acute left heart failure: 96.55% vs. 75.86%, total effective rate of bronchospasm: 93.10% vs. 65.52%, both P < 0.05). The difference of serum NT-proBNP before and after treatment in combination therapy group and hormone therapy group was significantly higher than that in conventional treatment group (ng/L: 7 922.86±5 220.31, 7 314.92±4 450.28 vs. 4 644.79±3 388.23, all P < 0.05), and the difference of serum NT-proBNP before and after treatment in the combined treatment group was significantly higher than that in the hormone treatment group (P < 0.05). There were no significant differences in SBP difference, MAP difference, mortality and re-hospitalization rate among the 3 groups. No adverse reactions occurred in the 3 groups during treatment.@*CONCLUSIONS@#Shenfu injection combined with glucocorticoid is effective in the treatment of patients with acute left heart failure complicated with bronchospasm. It is superior to glucocorticoid and aminophylline in relieving bronchospasm, reducing NT-proBNP level and improving total effective rate, and has good prognosis and safety.


Subject(s)
Humans , Glucocorticoids/therapeutic use , Bronchial Spasm , Prospective Studies , Aminophylline/therapeutic use , Sodium Chloride/therapeutic use , Natriuretic Peptide, Brain , Peptide Fragments , Heart Failure/drug therapy , Diabetes Mellitus , Glucose
15.
Chinese Critical Care Medicine ; (12): 1262-1267, 2023.
Article in Chinese | WPRIM | ID: wpr-1010937

ABSTRACT

OBJECTIVE@#To investigate the association between the glucose-to-lymphocyte ratio (GLR) and prognosis of patients with sepsis-associated acute kidney injury (SA-AKI).@*METHODS@#Based on the Medical Information Mart for Intensive Care-IV (MIMIC-IV), SA-AKI patients aged ≥ 18 years were selected. According to the tertiles of GLR, the patients were divided into GLR1 group (GLR ≤ 4.97×10-9 mmol), GLR2 group (4.97×10-9 mmol < GLR < 9.75×10-9 mmol) and GLR3 group (GLR ≥ 9.75×10-9 mmol). Patients with SA-AKI were divided into survival group and death group according to whether they survived 28 days after admission. The patient's gender, age, vital signs, laboratory test results, comorbidities, sequential organ failure assessment (SOFA), acute physiology score III (APS III) score and treatment measures were extracted from the database. Kaplan-Meier survival analysis was used to make the survival curves of patients with SA-AKI at 28 days, 90 days, 180 days and 1 year. Multivariate Logistic regression analysis model was used to explore the independent risk factors of 28-day mortality in patients with SA-AKI. Receiver operator characteristic curve (ROC curve) was used to analyze the predictive efficacy of GLR for the prognosis of patients with SA-AKI.@*RESULTS@#A total of 1 524 patients with SA-AKI were included, with a median age of 68.28 (58.96, 77.24) years old, including 612 females (40.16%) and 912 males (59.84%). There were 507 patients in the GLR1 group, 509 patients in the GLR2 group and 508 patients in the GLR3 group. There were 1 181 patients in the 28-day survival group and 343 patients in the death group. Grouping according to GLR tertiles showed that with the increase of GLR, the 28-day, 90-day, 180-day and 1-year mortality of SA-AKI patients gradually increased (28-day mortality were 11.64%, 22.00%, 33.86%, respectively; 90-day mortality were 15.98%, 26.72%, 40.55%, respectively; 180-day mortality were 17.16%, 28.29% and 41.73%, and the 1-year mortality were 17.95%, 29.27% and 42.72%, respectively, all P < 0.01). According to 28-day survival status, the GLR of the death group was significantly higher than that of the survival group [×10-9 mmol: 9.81 (5.75, 20.01) vs. 6.44 (3.64, 10.78), P < 0.01]. Multivariate Logistic regression analysis showed that GLR was an independent risk factor for 28-day mortality in patients with SA-AKI [when GLR was used as a continuous variable: odds ratio (OR) = 1.065, 95% confidence interval (95%CI) was 1.045-1.085, P < 0.001; when GLR was used as a categorical variable, compared with GLR1 group: GLR2 group OR = 1.782, 95%CI was 1.200-2.647, P = 0.004; GLR3 group OR = 2.727, 95%CI was 1.857-4.005, P < 0.001]. ROC curve analysis showed that the area under the ROC curve (AUC) of GLR for predicting 28-day mortality in patients with SA-AKI was 0.674, when the optimal cut-off value was 8.769×10-9 mmol, the sensitivity was 57.1% and the specificity was 67.1%. The predictive performance was improved when GLR was combined with APS III score and SOFA score, and the AUC was 0.806, the sensitivity was 74.6% and the specificity was 71.4%.@*CONCLUSIONS@#GLR is an independent risk factor of 28-day mortality in patients with SA-AKI, and high GLR is associated with poor prognosis in patients with SA-AKI.


Subject(s)
Male , Female , Humans , Blood Glucose , Glucose , ROC Curve , Prognosis , Sepsis/diagnosis , Acute Kidney Injury , Retrospective Studies , Intensive Care Units
16.
Chinese Critical Care Medicine ; (12): 1147-1149, 2023.
Article in Chinese | WPRIM | ID: wpr-1010917

ABSTRACT

Stress induced hyperglycemia is the body's protect response against strong (patho-physiological and/or psychological) stress, sometimes the blood glucose level is too high due to out of the body's adjustment. Renal glucose threshold (about 9 mmol/L) is a window of glucose leak from capillary to interstitial tissue. It is important to keep blood glucose level < 9 mmol/L, for reducing vascular sclerosis as well as organs hypoperfusion, meanwhile pay attention to preventing more dangerous hypoglycemia. Glucose, as the main energy substrate, should be daily supply and its metabolism should be monitored. We used to talk "nutritional support". Support is conform the physiological ability of host, but therapy is to coordinate and change pathophysiology. So, nutritional support is not equal to nutritional therapy. For critical ill patients, we need to emphasize "nutritional therapy", i.e, do not give nutritional treatment without metabolic monitoring, make up for deficiencies and avoid metabolites overloading, rational adjustment to protect and coordinate organs function.


Subject(s)
Humans , Blood Glucose/metabolism , Critical Illness/therapy , Hyperglycemia/therapy , Nutritional Support , Glucose
17.
International Journal of Oral Science ; (4): 37-37, 2023.
Article in English | WPRIM | ID: wpr-1010692

ABSTRACT

Oral potentially malignant disorders (OPMDs) are precursors of oral squamous cell carcinoma (OSCC). Deregulated cellular energy metabolism is a critical hallmark of cancer cells. Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC1α) plays vital role in mitochondrial energy metabolism. However, the molecular mechanism of PGC1α on OPMDs progression is less unclear. Therefore, we investigated the effects of knockdown PGC1α on human dysplastic oral keratinocytes (DOKs) comprehensively, including cell proliferation, cell cycle, apoptosis, xenograft tumor, mitochondrial DNA (mtDNA), mitochondrial electron transport chain complexes (ETC), reactive oxygen species (ROS), oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and glucose uptake. We found that knockdown PGC1α significantly inhibited the proliferation of DOKs in vitro and tumor growth in vivo, induced S-phase arrest, and suppressed PI3K/Akt signaling pathway without affecting cell apoptosis. Mechanistically, downregulated of PGC1α decreased mtDNA, ETC, and OCR, while enhancing ROS, glucose uptake, ECAR, and glycolysis by regulating lactate dehydrogenase A (LDHA). Moreover, SR18292 (an inhibitor of PGC1α) induced oxidative phosphorylation dysfunction of DOKs and declined DOK xenograft tumor progression. Thus, our work suggests that PGC1α plays a crucial role in cell proliferation by reprograming energy metabolism and interfering with energy metabolism, acting as a potential therapeutic target for OPMDs.


Subject(s)
Humans , Carcinoma, Squamous Cell/metabolism , Cell Proliferation , DNA, Mitochondrial , Energy Metabolism , Glucose , Mouth Neoplasms/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Phosphatidylinositol 3-Kinases , Reactive Oxygen Species
18.
Journal of Zhejiang University. Science. B ; (12): 1106-1122, 2023.
Article in English | WPRIM | ID: wpr-1010586

ABSTRACT

With the development of modern sequencing techniques and bioinformatics, genomes that were once thought to be noncoding have been found to encode abundant functional micropeptides (miPs), a kind of small polypeptides. Although miPs are difficult to analyze and identify, a number of studies have begun to focus on them. More and more miPs have been revealed as essential for energy metabolism homeostasis, immune regulation, and tumor growth and development. Many reports have shown that miPs are especially essential for regulating glucose and lipid metabolism and regulating mitochondrial function. MiPs are also involved in the progression of related diseases. This paper reviews the sources and identification of miPs, as well as the functional significance of miPs for metabolism-related diseases, with the aim of revealing their potential clinical applications.


Subject(s)
Humans , Open Reading Frames , Peptides , Glucose , Genome , Metabolic Diseases
19.
Chinese Journal of Biotechnology ; (12): 4927-4938, 2023.
Article in Chinese | WPRIM | ID: wpr-1008069

ABSTRACT

In order to investigate the enzyme production mechanism of yak rumen-derived anaerobic fungus Orpinomyces sp. YF3 under the induction of different carbon sources, anaerobic culture tubes were used for in vitro fermentation. 8 g/L of glucose (Glu), filter paper (Flp) and avicel (Avi) were respectively added to 10 mL of basic culture medium as the sole carbon source. The activity of fiber-degrading enzyme and the concentration of volatile fatty acid in the fermentation liquid were detected, and the enzyme producing mechanism of Orpinomyces sp. YF3 was explored by transcriptomics. It was found that, in glucose-induced fermentation solution, the activities of carboxymethyl cellulase, microcrystalline cellulase, filter paper enzyme, xylanase and the proportion of acetate were significantly increased (P < 0.05), the proportion of propionate, butyrate, isobutyrate were significantly decreased (P < 0.05). The results of transcriptome analysis showed that there were 5 949 differentially expressed genes (DEGs) between the Glu group and the Flp group, 10 970 DEGs between the Glu group and the Avi group, and 6 057 DEGs between the Flp group and the Avi group. It was found that the DEGs associated with fiber degrading enzymes were significantly up-regulated in the Glu group. Gene ontology (GO) function enrichment analysis identified that DEGs were mainly associated with the xylan catabolic process, hemicellulose metabolic process, β-glucan metabolic process, cellulase activity, endo-1,4-β-xylanase activity, cell wall polysaccharide metabolic process, carbohydrate catabolic process, glucan catabolic process and carbohydrate metabolic process. Moreover, the differentially expressed pathways associated with fiber degrading enzymes enriched by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were mainly starch and sucrose metabolic pathways and other glycan degradation pathways. In conclusion, Orpinomyces sp. YF3 with glucose as carbon source substrate significantly increased the activity of cellulose degrading enzyme and the proportion of acetate, decreased the proportion of propionate, butyrate and isobutyrate. Furthermore, the degradation ability and energy utilization efficiency of fungus in the presence of glucose were improved by means of regulating the expression of cellulose degrading enzyme gene and participating in starch and sucrose metabolism pathway, and other glycan degradation pathways, which provides a theoretical basis for the application of Orpinomyces sp. YF3 in practical production and facilitates the application of Orpinomyces sp. YF3 in the future.


Subject(s)
Animals , Cattle , Neocallimastigales/metabolism , Anaerobiosis , Rumen/microbiology , Propionates/metabolism , Isobutyrates/metabolism , Cellulose/metabolism , Fungi , Starch/metabolism , Glucose/metabolism , Acetates , Sucrose/metabolism , Cellulases , Cellulase
20.
Chinese Journal of Biotechnology ; (12): 4694-4707, 2023.
Article in Chinese | WPRIM | ID: wpr-1008051

ABSTRACT

β-glucosidase has important applications in food, pharmaceutics, biomass conversion and other fields, exploring β-glucosidase with strong adaptability and excellent properties thus has received extensive interest. In this study, a novel glucosidase from the GH1 family derived from Cuniculiplasma divulgatum was cloned, expressed, and characterized, aiming to find a better β-glucosidase. The amino acid sequences of GH1 family glucosidase derived from C. divulgatum were obtained from the NCBI database, and a recombinant plasmid pET-30a(+)-CdBglA was constructed. The recombinant protein was induced to express in Escherichia coli BL21(DE3). The enzymatic properties of the purified CdBglA were studied. The molecular weight of the recombinant CdBglA was 56.0 kDa. The optimum pH and temperature were 5.5 and 55 ℃, respectively. The enzyme showed good pH stability, 92.33% of the initial activity could be retained when treated under pH 5.5-11.0 for 1 h. When pNPG was used as a substrate, the kinetic parameters Km, Vmax and Kcat/Km were 0.81 mmol, 291.99 μmol/(mg·min), and 387.50 s-1 mmol-1, respectively. 90.33% of the initial enzyme activity could be retained when CdBglA was placed with various heavy metal ions at a final concentration of 5 mmol/L. The enzyme activity was increased by 28.67% under 15% ethanol solution, remained unchanged under 20% ethanol, and 43.68% of the enzyme activity could still be retained under 30% ethanol. The enzyme has an obvious activation effect at 0-1.5 mol/L NaCl and can tolerate 0.8 mol/L glucose. In conclusion, CdBglA is an acidic and mesophilic enzyme with broad pH stability and strong tolerance to most metal ions, organic solvents, NaCl and glucose. These characteristics may facilitate future theoretical research and industrial production.


Subject(s)
beta-Glucosidase , Sodium Chloride , Temperature , Glucose , Ethanol/chemistry , Ions , Hydrogen-Ion Concentration , Enzyme Stability , Substrate Specificity
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