Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 74.720
Filtrar
1.
Nat Commun ; 11(1): 4611, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32929072

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) and cancer-associated cachexia (CAC) are multifactorial and characterized by dysregulated inflammatory networks. Whether the proinflammatory cytokine IL-20 is involved in the complex networks of PDAC and CAC remains unclear. Here, we report that elevated IL-20 levels in tumor tissue correlate with poor overall survival in 72 patients with PDAC. In vivo, we establish a transgenic mouse model (KPC) and an orthotopic PDAC model and examine the therapeutic efficacy of an anti-IL-20 monoclonal antibody (7E). Targeting IL-20 not only prolongs survival and attenuates PD-L1 expression in both murine models but also inhibits tumor growth and mitigates M2-like polarization in the orthotopic PDAC model. Combination treatment with 7E and an anti-PD-1 antibody shows better efficacy in inhibiting tumor growth than either treatment alone in the orthotopic PDAC model. Finally, 7E mitigates cachexic symptoms in CAC models. Together, we conclude IL-20 is a critical mediator in PDAC progression.


Assuntos
Anticorpos Monoclonais/farmacologia , Antígeno B7-H1/metabolismo , Interleucinas/antagonistas & inibidores , Modelos Biológicos , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Animais , Linfócitos T CD8-Positivos/metabolismo , Caquexia , Carcinoma Pulmonar de Lewis/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Interleucinas/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Neoplasias Pancreáticas/imunologia , Análise de Sobrevida , Resultado do Tratamento , Triglicerídeos/sangue , Regulação para Cima/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Medicine (Baltimore) ; 99(36): e21792, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899007

RESUMO

Major lipids making effects on the occurrence of acute ischemic stroke (AIS) is well recognized, but their roles on stroke severity remain uncertain. To explore the exact roles of lipids playing on stroke severity and the possible mechanism, we conduct this observational study.Data was collected from patients with AIS from February 2008 to May 2012. The level of major lipids was compared among AIS groups with different severity and investigated the correlation. Also, the relationship existed between major lipids and bilirubin. Mechanism of major lipids playing on stroke severity was researched to determine if oxidative stress reflected by bilirubin.Lower triglyceride (TG) and higher high density lipoprotein cholesterol (HDL-C) were observed in severe stroke, and obvious correlation existed between TG and stroke severity or HDL-C and stroke severity. TG was associated negatively with direct bilirubin (DBIL) and total bilirubin (TBIL), and lower level of DBIL and TBIL were related to higher quartiles of TG. There was no obvious difference of DBIL and TBIL among the groups of quartiles of HDL-C. TG was the influence factor of stroke severity in severe stroke through multiple univariable logistic regression. But it was not the independent influence factor after multivariable logistic regression adjusted by DBIL or TBIL. However, HDL-C was the influence factor of stroke severity through both univariable and multivariable logistic regression.Lower TG or higher HDL-C predicted severer stroke. The effect of TG on stroke severity was mediated by bilirubin, not HDL-C.


Assuntos
Bilirrubina/sangue , HDL-Colesterol/sangue , Acidente Vascular Cerebral/sangue , Triglicerídeos/sangue , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Estresse Oxidativo , Índice de Gravidade de Doença
3.
Medicine (Baltimore) ; 99(35): e21654, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871878

RESUMO

The aim of this study is to investigate the levels of 25(OH)D, inflammation markers and glucose and fat metabolism indexes in pregnant women with Gestational diabetes mellitus (GDM).One hundred and ten cases GDM and 100 cases healthy pregnant women in the First People's Hospital of Lianyungang City from October 2016 to December 2018 were recruited for this observational cross-sectional study. Each participant's anthropometric and demographic data was recorded. Blood samples were collected and analyzed to determine the levels of 25(OH)D, high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), fasting blood glucose, fasting blood insulin, hemoglobin A1c (HbA1c), homeostasis model assessment of insulin resistance (HOMA-IR), cholesterol and triglycerides.Inflammatory markers and glucose and fat metabolism indexes were all significantly higher in the GDM group than that in the control group, while Serum 25(OH)D level in the GDM group was significantly lower. Serum 25(OH)D levels were negatively correlated with hs-CRP, while not with TNF-α. Furthermore, Serum 25(OH)D, hs-CRP and TNF-α levels were all associated with increased risk of developing GDM.Nowadays, the reports on the association between 25(OH)D level and GDM were controversial. Our results are consistent with the view that there was association between 25(OH)D level and GDM, and expand the literature by showing the roles of 25(OH)D, inflammation markers as well as glucose and fat metabolism indexes in the risk of developing GDM in the pregnant women with the low overall levels of 25(OH)D before delivery. This broadens our knowledge on the pathophysiology of GDM, which may be helpful in prevention and treatment of GDM.


Assuntos
Glicemia/metabolismo , Diabetes Gestacional/sangue , Vitamina D/análogos & derivados , Adulto , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , China , Colesterol/sangue , Estudos Transversais , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Insulina/sangue , Resistência à Insulina , Gravidez , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/sangue , Vitamina D/sangue
4.
Medicine (Baltimore) ; 99(35): e21574, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871873

RESUMO

The prevalence of the metabolic syndrome (MS) is increasing in China, but there are disparities between urban and rural populations, and across different regions.To examine the prevalence and risk factors of MS in the rural area of Qianjiang (Southwest China).From March 2016 to June 2018, 6 townships in the Qianjiang District of Chongqing Municipality were selected for a cross-sectional study of the residents in rural areas. Demographics and medical history were collected using a questionnaire. Anthropometry and blood pressure were obtained by physical examination. Blood lipids, fasting plasma glucose, and 2-h postprandial glucose were measured.A total of 2949 (1067 males and 1882 females) were included. The mean age was 63.8 ±â€Š10.7 years. The prevalence of MS in the study population was 16.8% (496/2949). The prevalence of MS was 7.4% in men, 22.2% in women, 15.7% in Han, 18.1% in Tujia, and 14.8% in Miao. According to age, the prevalence of MS was 10.6%, 17.0%, and 18.3% in the 30-50, 50-69, and ≥ 70 years groups. The multivariable analysis showed that female sex (OR = 33.36, 95%CI: 17.0-65.53), dyslipidemia (OR = 4.71, 95%CI: 1.73-12.82), kidney diseases (OR = 2.32, 95%CI: 1.37-3.94), waistline (OR = 1.39, 95%CI: 1.33-1.46), high-density lipoprotein cholesterol (OR = 0.12, 95%CI: 0.06-0.23), triglycerides (OR = 1.52, 95%CI: 1.31-1.76), alanine aminotransferase (OR = 0.98, 95%CI: 0.97-1.00), γ-glutamyltransferase (OR = 1.00, 95%CI: 1.00-1.01), and glycated hemoglobin (OR = 1.31, 95%CI: 1.08-1.59) were independently associated with MS.The prevalence of MS was 16.8% in Qianjiang. Female sex, kidney diseases, alanine aminotransferase, and γ-glutamyltransferase were independent risk factors for MS.


Assuntos
Síndrome Metabólica/sangue , Síndrome Metabólica/epidemiologia , População Rural/tendências , Idoso , Alanina Transaminase/sangue , Antropometria , Glicemia/análise , Pressão Sanguínea/fisiologia , China/epidemiologia , HDL-Colesterol/sangue , Estudos Transversais , Dislipidemias/epidemiologia , Jejum/sangue , Feminino , Humanos , Nefropatias/epidemiologia , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Fatores Sexuais , Triglicerídeos/sangue , gama-Glutamiltransferase/sangue
5.
Medicine (Baltimore) ; 99(33): e21647, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872028

RESUMO

Prevalence of postpartum depression (PD) in Chinese women is rising and its associated factors are not well known. In this study we aim to explore the associations between nutritional factors in pregnancy and the risk of PD in Chinese women.A case-control study was performed in our hospital during January 2016 to June 2019. A food frequency questionnaire was designed to collect food consumption before the childbirth preceding month. Nutrition related biochemical indicators including fasting blood-glucose (GLU), total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), and uric acid in the third trimester of pregnancy were detected. Logistic regression model was applied to compute odds ratio (OR) and its corresponding 95% confidence interval (CI).There were 565 participants in this study, which comprised 182 individuals with PD and 383 individuals without. Patients with PD had higher odds of increased GLU (OR=2.62, 95%CI = 1.67-4.11), TC (OR = 1.73 95%CI = 1.22-2.46), TG (OR = 2.43, 95%CI = 1.55-3.81), and LDL (OR = 3.41, 95%CI = 2.09-5.57), but decreased HDL (OR = 3.41, 95%CI = 2.09-5.57) during pregnancy. With respect to uric acid, there was lack of no statistical association (OR = 2.23, 95%CI = 0.82-6.26). Food frequency questionnaire indicated a higher meat intake, but a lower vegetable, fruit, fish, and poultry intake in patients with PD during pregnancy.Increased GLU, TC, TG, and LDL, but decreased HDL in later stages of pregnancy might be associated with PD.


Assuntos
Depressão Pós-Parto/etiologia , Avaliação Nutricional , Adulto , Biomarcadores/sangue , Glicemia/análise , Estudos de Casos e Controles , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Gravidez , Terceiro Trimestre da Gravidez , Fatores de Risco , Triglicerídeos/sangue
6.
Lipids Health Dis ; 19(1): 204, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32892746

RESUMO

BACKGROUND: The purpose of the study is to describe the blood lipid levels of patients diagnosed with coronavirus disease 2019 (COVID-19) and to analyze the correlation between blood lipid levels and the prognosis of COVID-19 patients. METHODS: In the clinical retrospective analysis, a total of 228 adults infected with COVID-19 were enrolled between January 17, 2020 and March 14, 2020, in Changsha, China. One thousand one hundred and forty healthy participants with matched age and gender were used as control. Median with interquartile range and Mann-Whitney test were adopted to describe and analyze clinical data. The Kaplan-Meier (KM) curve and Cox regression analysis were used to analyze the correlation between high-density lipoprotein cholesterol (HDL-C) and the severity of COVID-19. RESULTS: Compared with control, COVID-19 patients showed significantly lower levels of total cholesterol (TC) [median, 3.76 vs 4.65 mmol/L, P = 0.031], triglyceride [median, 1.08 vs 1.21 mmol/L, P <  0.001], low-density lipoprotein cholesterol (LDL-C) [median, 2.63 vs 2.83 mmol/L, P <  0.001], and HDL-C [median, 0.78 vs 1.37 mmol/L, P <  0.001], while compared with non-severe patients, severe COVID-19 patients only presented lower levels of HDL-C [median, 0.69 vs 0.79 mmol/L, P = 0.032]. In comparison with patients with high HDL-C, patients with low HDL-C showed a higher proportion of male (69.57% vs 45.60%, P = 0.004), higher levels of C-reactive protein (CRP) (median, 27.83 vs 12.56 mg/L, P <  0.001) and higher proportion of severe events (36.96% vs 14.84%, P = 0.001). Moreover, patients with low HDL-C at admission showed a higher risk of developing severe events compared with those with high HDL-C (Log Rank P = 0.009). After adjusting for age, gender and underlying diseases, they still had elevated possibility of developing severe cases than those with high HDL-C (HR 2.827, 95% CI 1.190-6.714, P = 0.019). CONCLUSIONS: HDL-C level was lower in COVID-19 adult patients, and low HDL-C in COVID-19 patients was correlated with a higher risk of developing severe events.


Assuntos
Betacoronavirus , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Infecções por Coronavirus/fisiopatologia , Pneumonia Viral/fisiopatologia , Adulto , Proteína C-Reativa/análise , China , Colesterol/sangue , Infecções por Coronavirus/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Triglicerídeos/sangue
7.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(8): 1141-1147, 2020 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-32895189

RESUMO

OBJECTIVE: To investigate the triglyceride (TG)-lowering effects of PCSK9 inhibitor in patients with in different baseline triglyceride levels. METHODS: Between February, 2019 and March, 2020, a total of 59 patients were treated with PCSK9 inhibitor (Evolocumab) in 5 hospitals, including Nanfang Hospital, Guangdong Provincial People's Hospital, First Affiliated Hospital of Sun Yat-sen University, Foshan Nanhai District People's Hospital and Yulin First People's Hospital. According to baseline triglyceride levels, the patients were divided into normal TG group (< 1.70 mmol/L, n=24), mild hypertriglyceridemia group (1.70-2.29 mmol/L, n=11), moderate hypertriglyceridemia group (2.30-5.63 mmol/L, n=13), and severe hypertriglyceridemia group (≥5.64 mmol/L, n=11), and the changes in TG level after the treatment were compared among the 4 groups. RESULTS: In the groups with normal and mildly elevated baseline TG level, the patients did not show significant changes in TG levels after the treatment. In patients with moderately and severely elevated baseline TG levels, treatment with PCSK9 inhibitor significantly reduced their TG levels (P < 0.005). CONCLUSIONS: PCSK9 inhibitor has a significant TG-lowering effect in patients with moderate to severe hypertriglyceridemia but not in patients with only mildly elevated baseline TG level.


Assuntos
Hipertrigliceridemia , Humanos , Hipolipemiantes , Pró-Proteína Convertase 9 , Triglicerídeos
8.
Nat Commun ; 11(1): 4107, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32796836

RESUMO

Foamy macrophages, which have prominent lipid droplets (LDs), are found in a variety of disease states. Toll-like receptor agonists drive triacylglycerol (TG)-rich LD development in macrophages. Here we explore the basis and significance of this process. Our findings indicate that LD development is the result of metabolic commitment to TG synthesis on a background of decreased fatty acid oxidation. TG synthesis is essential for optimal inflammatory macrophage activation as its inhibition, which prevents LD development, has marked effects on the production of inflammatory mediators, including IL-1ß, IL-6 and PGE2, and on phagocytic capacity. The failure of inflammatory macrophages to make PGE2 when TG-synthesis is inhibited is critical for this phenotype, as addition of exogenous PGE2 is able to reverse the anti-inflammatory effects of TG synthesis inhibition. These findings place LDs in a position of central importance in inflammatory macrophage activation.


Assuntos
Inflamação/metabolismo , Lipidômica/métodos , Triglicerídeos/metabolismo , Animais , Células Cultivadas , Citometria de Fluxo , Glucose/metabolismo , Glicerol/metabolismo , Células HEK293 , Humanos , Metabolismo dos Lipídeos/fisiologia , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Confocal , Microscopia Eletrônica , Palmitatos/metabolismo , Análise de Sequência de RNA
9.
PLoS Genet ; 16(8): e1008941, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32760060

RESUMO

Apolipoprotein B-containing lipoproteins (B-lps) are essential for the transport of hydrophobic dietary and endogenous lipids through the circulation in vertebrates. Zebrafish embryos produce large numbers of B-lps in the yolk syncytial layer (YSL) to move lipids from yolk to growing tissues. Disruptions in B-lp production perturb yolk morphology, readily allowing for visual identification of mutants with altered B-lp metabolism. Here we report the discovery of a missense mutation in microsomal triglyceride transfer protein (Mtp), a protein that is essential for B-lp production. This mutation of a conserved glycine residue to valine (zebrafish G863V, human G865V) reduces B-lp production and results in yolk opacity due to aberrant accumulation of cytoplasmic lipid droplets in the YSL. However, this phenotype is milder than that of the previously reported L475P stalactite (stl) mutation. MTP transfers lipids, including triglycerides and phospholipids, to apolipoprotein B in the ER for B-lp assembly. In vitro lipid transfer assays reveal that while both MTP mutations eliminate triglyceride transfer activity, the G863V mutant protein unexpectedly retains ~80% of phospholipid transfer activity. This residual phospholipid transfer activity of the G863V mttp mutant protein is sufficient to support the secretion of small B-lps, which prevents intestinal fat malabsorption and growth defects observed in the mttpstl/stl mutant zebrafish. Modeling based on the recent crystal structure of the heterodimeric human MTP complex suggests the G865V mutation may block triglyceride entry into the lipid-binding cavity. Together, these data argue that selective inhibition of MTP triglyceride transfer activity may be a feasible therapeutic approach to treat dyslipidemia and provide structural insight for drug design. These data also highlight the power of yolk transport studies to identify proteins critical for B-lp biology.


Assuntos
Proteínas de Transporte/genética , Lipídeos/genética , Lipoproteínas/genética , Triglicerídeos/genética , Animais , Fígado Gorduroso/genética , Fígado Gorduroso/patologia , Trato Gastrointestinal/metabolismo , Humanos , Imunoprecipitação , Gotículas Lipídicas/metabolismo , Lipoproteínas/metabolismo , Mutação de Sentido Incorreto/genética , Mutação Puntual/genética , Transporte Proteico/genética , Triglicerídeos/metabolismo , Peixe-Zebra/genética
10.
Yakugaku Zasshi ; 140(8): 1051-1061, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32741863

RESUMO

It has been reported that medium-chain triglyceride (MCT) have various physiological functions, such as anti-obesity and hypolipidemic effects. They can also elicit increased disaccharidase activity and intestinal cell proliferation. However, a meta-analysis of randomized controlled trials, comparing the effects of MCT on weight loss and body composition, detected commercial bias. Additional research on the physiological functions is needed in order to have conclusive evidence. Thus, we sought to evaluate the various functions of MCT by conducting a feeding study in rats. Rats fed a diet containing 15% (w/w) MCT, had significantly lower visceral fat weight, plasma and liver lipid concentrations; they had significantly higher intestinal maltase and glucoamylase activities; and they had a greater number of Ki-67 positive cells/crypt, compared to the rats fed a diet containing 15% (w/w) lard. The effects of a diet containing 5% (w/w) MCT was observed only for plasma cholesterol levels and the number of Ki-67 positive cells/crypt; in which some results were found to be inconsistent with previous reports. These results indicate that physiological functions of MCT are numerous and need to be confirmed by additional research.


Assuntos
Glucana 1,4-alfa-Glucosidase/metabolismo , Intestino Delgado/enzimologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Triglicerídeos/administração & dosagem , Triglicerídeos/farmacologia , alfa-Glucosidases/metabolismo , Animais , Fármacos Antiobesidade , Proliferação de Células/efeitos dos fármacos , Dieta , Hipolipemiantes , Intestino Delgado/citologia , Gordura Intra-Abdominal , Antígeno Ki-67/metabolismo , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos Sprague-Dawley , Triglicerídeos/química
11.
Nat Commun ; 11(1): 3944, 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769983

RESUMO

Triacylglycerols (TG) are synthesized at the endoplasmic reticulum (ER) bilayer and packaged into organelles called lipid droplets (LDs). LDs are covered by a single phospholipid monolayer contiguous with the ER bilayer. This connection is used by several monotopic integral membrane proteins, with hydrophobic membrane association domains (HDs), to diffuse between the organelles. However, how proteins partition between ER and LDs is not understood. Here, we employed synthetic model systems and found that HD-containing proteins strongly prefer monolayers and returning to the bilayer is unfavorable. This preference for monolayers is due to a higher affinity of HDs for TG over membrane phospholipids. Protein distribution is regulated by PC/PE ratio via alterations in monolayer packing and HD-TG interaction. Thus, HD-containing proteins appear to non-specifically accumulate to the LD surface. In cells, protein editing mechanisms at the ER membrane would be necessary to prevent unspecific relocation of HD-containing proteins to LDs.


Assuntos
Membrana Celular/metabolismo , Bicamadas Lipídicas/metabolismo , Gotículas Lipídicas/metabolismo , Proteínas de Membrana/metabolismo , Triglicerídeos/metabolismo , Dicroísmo Circular , Retículo Endoplasmático/metabolismo , Proteínas de Membrana/química , Simulação de Dinâmica Molecular , Domínios Proteicos , Transporte Proteico , Triglicerídeos/química
12.
Life Sci ; 257: 118125, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32702444

RESUMO

AIM: Nonalcoholic fatty liver disease (NAFLD) is a growing health problem worldwide. Impaired autophagy has been linked to NAFLD pathogenesis. Whether transfer RNA (tRNA)-derived fragments (tRFs) regulate the progression of NAFLD via autophagy is not clear. Here, we aimed to identify autophagy- or adipogenesis-related tRFs and investigate their roles in NAFLD. METHODS: Small RNA sequencing was performed on NAFLD and control mice, and candidate tRFs were validated using quantitative reverse transcription PCR (qRT-PCR). The role of a key tRF was investigated using Oil red O staining, western blotting, qRT-PCR and a luciferase reporter assay. KEY FINDINGS: In NAFLD mice, the expression of p62 was increased and the ratio of LC3B-II/LC3-I was decreased compared to control mice. We identified nine differentially expressed tRFs, among which tRF-3001b was found to be significantly upregulated in NAFLD mice compared to the control liver tissues. Autophagy was decreased in FA (fatty acids)-induced LO2 cells, while silencing of tRF-3001b significantly abrogated the decrease in autophagy and increase in lipid formation. Moreover, chloroquine (CQ) dramatically abrogated the effect of tRF-3001b inhibition on lipid formation. Mechanistically, tRF-3001b targeted and inhibited the expression of the autophagy-related gene Prkaa1. In vivo, tRF-3001b silencing significantly improved pathology and decreased the levels of triglycerides and cholesterol in NAFLD mice, while CQ dramatically abrogated the effect of tRF-3001b deficiency. SIGNIFICANCE: tRF-3001b may aggravate the development of NAFLD by inhibiting autophagy via targeting Prkaa1.


Assuntos
Autofagia , Hepatopatia Gordurosa não Alcoólica/metabolismo , RNA de Transferência/metabolismo , Animais , Western Blotting , Linhagem Celular , Colesterol/sangue , Ensaio de Imunoadsorção Enzimática , Humanos , Metabolismo dos Lipídeos , Camundongos , Camundongos Endogâmicos C57BL , RNA de Transferência/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de RNA , Triglicerídeos/sangue
13.
Zhongguo Zhong Yao Za Zhi ; 45(13): 3203-3210, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-32726030

RESUMO

The animal model of hyperlipidemia in rats was established to investigate the lipid-lowering effect and mechanism of Danhong Injection on hyperlipidemic rats. SD rats were selected as the research object. The rats in normal group were fed with basic diet, and the rats in other groups were fed with high-fat diet to establish hyperlipidemia model. The successfully modeled rats were randomly divided into model group, Danhong Injection low, medium, high dose(1.0, 2.0, 4.0 mL·kg~(-1)) groups, and simvastatin(2.0 mg·kg~(-1)) group. Danhong Injection groups received intraperitoneal administration, and simvastatin group received intragastrical administration, once a day for 4 weeks. At the first, second, third, and fourth weekends after administration, blood was collected from the orbital vein to detect the levels of total cholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-C), and high-density lipoprotein cholesterol(HDL-C), and then the atherosclerosis index(AI) was calculated. After 4 weeks of administration, the animals were sacrificed, and their heart, liver, spleen, lung, kidney and adipose tissue were extracted and weighed respectively to calculate the organ index of each group. The expressions of acyl-coaoxidase 1(Acox1), adenosine 5'-monophosphate(AMP)-activated protein kinase alpha(AMPK-α), bile salt export pump(BSEP), peroxisome proliferator-activated receptor gamma(PPAR-γ), catalase(CAT) and superoxide dismutase(SOD) mRNA in liver tissues were detected by fluorescence quantitative PCR; the content of cholesteryl ester transfer protein(CETP) and lecithin cholesterol acyltransferase(LCAT) in serum was detected by ELISA. The results showed that as compared with the normal group, the levels of serum TC, TG and LDL-C in the model group were significantly increased, and the level of HDL-C was significantly decreased, indicating that the hyperlipidemia rat model was successfully constructed. As compared with the model group, Danhong Injection could decrease the contents of TC, TG, LDL-C and increase the content of HDL-C in hyperlipidemia rats; reduce the body weight of hyperlipidemia rats, and reduce the liver weight, liver index, fat weight and fat index; it had no significant effect on the main organ indexes such as heart, spleen, lung and kidney; but it could increase the expressions of Acox1, AMPK-α, BSEP, PPAR-γ, CAT and SOD mRNA in liver tissues of rats; it could also reduce the level of CETP and increase the level of LCAT in serum; and the regulatory effect of Danhong Injection groups all showed a dose-dependent effect. It can be concluded that Danhong Injection can regulate the blood lipid contents, reduce the blood lipid levels and alleviate the accumulation of body fat in rats with hyperlipidemia. The mechanism may be related to inhibiting lipid metabolism disorder and oxidative stress induced by high-fat diet feeding, and improving the imbalance of lipid transport system.


Assuntos
Hiperlipidemias , Animais , Dieta Hiperlipídica , Medicamentos de Ervas Chinesas , Metabolismo dos Lipídeos , Lipídeos , Fígado , Ratos , Ratos Sprague-Dawley , Triglicerídeos
14.
Intern Med ; 59(14): 1705-1710, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32669515

RESUMO

Objective Lipoprotein (a), or Lp (a), has been shown to be associated with the development of chronic kidney disease (CKD) in populations of various ethnicities. This study aimed to investigate the association between serum Lp (a) and CKD in Japanese patients. Methods A total of 6,130 subjects who underwent a serum Lp (a) level assessment for any reason (e.g. any type of surgery requiring prolonged bed rest or risk factors for atherosclerosis, such as hypertension or diabetes) were retrospectively investigated at Kanazawa University Hospital from April 2004 to March 2014. Of these, 1,895 subjects were excluded because of the lack of clinical data. Subjects were assessed for Lp (a), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, hypertension, diabetes, smoking, body mass index (BMI), coronary artery disease (CAD), and CKD (stage ≥3). Results When the study subjects were divided into quartiles of Lp (a) levels, significant trends were observed with regard to the presence of CKD (p = 2.7×10-13). A multiple regression analysis showed that Lp (a) was significantly associated with CKD [odds ratio (OR), 1.12; 95% confidence interval (CI), 1.08-1.17; p = 1.3×10-7, per 10 mg/dL], independent of other classical risk factors, including age, gender, BMI, hypertension, diabetes, smoking, LDL cholesterol, and triglycerides. Under these conditions, Lp (a) was significantly associated with CAD (OR = 1.11, 95% CI = 1.06-1.16; p = 1.7×10-6, per 10 mg/dL), independent of other risk factors. Conclusion Serum Lp (a) was associated with CKD, independent of other classical risk factors in a Japanese population.


Assuntos
Hiperlipidemias/complicações , Lipoproteína(a)/sangue , Insuficiência Renal Crônica/etiologia , Adulto , Idoso , Doenças Cardiovasculares/complicações , LDL-Colesterol/sangue , Doença da Artéria Coronariana/sangue , Feminino , Hospitalização , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Razão de Chances , Curva ROC , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Triglicerídeos/sangue
15.
Life Sci ; 257: 118028, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32615185

RESUMO

AIMS: Sertoli cells (SCs) play an important role in the process of spermatogenesis. SCs provide energy for germ cells (GCs) and themselves through glycolysis and fatty acid oxidation (FAO) respectively. High fat diet (HFD) impairs spermatogenesis by damaging function of SCs, however whether HFD disrupts energy metabolism in SCs remains unclear. MAIN METHODS: To explore this hypothesis, we built male Wistar rat model fed on HFD and cultured rats' primary SCs with palmitic acid (PA). Rats' fertility and sperm quality were evaluated in vivo. Glycolysis, lactate production and mitochondrial respiration were assessed by using extracellular flux analyzer, and the expression of enzymes involved in glucose and FAO was analyzed by Real-Time PCR or Western Blotting. KEY FINDINGS: The showed that the sperm concentration and pups per litter significantly decreased in rats fed on HFD compared to those rats fed on normal diet. There was an elevation of lactate levels in testicular tissue of rats fed on HFD and primary SCs exposed to PA. In vitro, PA increased glycolytic flux, and lactate production, and the levels of carnitine palmitoyltransferase I (CPT1) and long chain acyl-CoA dehydrogenase (LCAD) which were two key enzymes for fatty acid ß oxidation. Further analysis showed that mitochondrial respiration was impaired by PA, followed by the decrease in ATP turnover, maximal respiration and the increase in proton leak. SIGNIFICANCE: Taken together, the elevated lactate level, lipid metabolism disorder and mitochondrial dysfunction caused by HFD lead to SCs dysfunction, which ultimately leads to decreased sperm quality.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Células de Sertoli/metabolismo , Espermatogênese/fisiologia , Animais , Metabolismo Energético , Ácidos Graxos/metabolismo , Glucose/metabolismo , Glicólise , Insulina/metabolismo , Metabolismo dos Lipídeos/fisiologia , Masculino , Oxirredução , Ácido Palmítico , Ratos , Ratos Wistar , Triglicerídeos/metabolismo
17.
BMC Infect Dis ; 20(1): 473, 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32620082

RESUMO

BACKGROUND: People living with the Human Immunodeficiency Virus (PLHIV) have an increased susceptibility to develop non-communicable diseases such as cardiovascular disease (CVD). Infection with HIV contributes to the development of CVD independent of traditional risk factors, with endothelial dysfunction being the central physiological mechanism. While HIV-related mortality is declining due to antiretroviral treatment (ART), the number of deaths due to CVD is rising in South Africa - the country with the highest number of PLHIV and the world's largest ART programme. The EndoAfrica study was developed to determine whether HIV infection and ART are associated with cardiovascular risk markers and changes in vascular structure and function over 18 months in adults from different provinces of South Africa. This paper describes the rationale, methodology and baseline cohort profile of the EndoAfrica study conducted in the North West Province, South Africa. METHODS: In this case-control study, conducted between August 2017 and June 2018, 382 volunteers of African descent (276 women; 106 men), comprising of 278 HIV infected and 104 HIV free individuals were included. We measured health behaviours, a detailed cardiovascular profile, and performed biomarker analyses. We compared baseline characteristics, blood pressure, vascular function and biochemical markers between those infected and HIV free. RESULTS: At baseline, the HIV infected participants were older (43 vs 39 years), less were employed (21% vs 40%), less had a tertiary education (7% vs 16%) and their body mass index was lower (26 vs 29 kg/m2) than that of the HIV free participants. While the cardiovascular profile, flow-mediated dilation and pulse wave velocity did not differ, glycated haemoglobin was lower (p = 0.017) and total cholesterol, high density lipoprotein cholesterol, triglycerides, gamma-glutamyltransferase and tobacco use were higher (all p < 0.047) in PLHIV. CONCLUSION: Despite PLHIV being older, preliminary cross-sectional analysis suggests that PLHIV being treated with ART do not have poorer endothelial or vascular function compared to the HIV free participants. More detailed analyses on the baseline and follow-up data will provide further clarity regarding the cardiovascular profile of South Africans living with HIV.


Assuntos
Síndrome de Imunodeficiência Adquirida/complicações , Síndrome de Imunodeficiência Adquirida/epidemiologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , HIV , Síndrome de Imunodeficiência Adquirida/sangue , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Adulto , Antirretrovirais/uso terapêutico , Biomarcadores/sangue , Pressão Sanguínea , Estudos de Casos e Controles , HDL-Colesterol/sangue , Estudos Transversais , Feminino , Hemoglobina A Glicada/análise , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Doenças não Transmissíveis , Análise de Onda de Pulso , Fatores de Risco , África do Sul/epidemiologia , Triglicerídeos/sangue
18.
PLoS One ; 15(7): e0235990, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32701948

RESUMO

BACKGROUND AND AIMS: Alcoholic steatohepatitis (ASH)-the inflammation of fatty liver-is caused by chronic alcohol consumption and represents one of the leading chronic liver diseases in Western Countries. ASH can lead to organ dysfunction or progress to hepatocellular carcinoma (HCC). Long-term alcohol abstinence reduces this probability and is the prerequisite for liver transplantation-the only effective therapy option at present. Elevated enzymatic activity of cytochrome P450 2E1 (CYP2E1) is known to be critically responsible for the development of ASH due to excessively high levels of reactive oxygen species (ROS) during metabolization of ethanol. Up to now, no rational drug discovery process was successfully initiated to target CYP2E1 for the treatment of ASH. METHODS: In this study, we applied a rational drug design concept to develop drug candidates (NCE) including preclinical studies. RESULTS: A new class of drug candidates was generated successfully. Two of the most promising small compounds named 12-Imidazolyl-1-dodecanol (abbr.: I-ol) and 1-Imidazolyldodecane (abbr.: I-an) were selected at the end of this process of drug discovery and developability. These new ω-imidazolyl-alkyl derivatives act as strong chimeric CYP2E1 inhibitors at a nanomolar range. They restore redox balance, reduce inflammation process as well as the fat content in the liver and rescue the physiological liver architecture of rats consuming continuously a high amount of alcohol. CONCLUSIONS: Due to its oral application and therapeutic superiority over an off-label use of the hepatoprotector ursodeoxycholic acid (UDCA), this new class of inhibitors marks the first rational, pharmaceutical concept in long-term treatment of ASH.


Assuntos
Inibidores do Citocromo P-450 CYP2E1/uso terapêutico , Citocromo P-450 CYP2E1/metabolismo , Fígado Gorduroso Alcoólico/tratamento farmacológico , Alcanos/síntese química , Alcanos/farmacologia , Alcanos/uso terapêutico , Animais , Citocromo P-450 CYP2E1/química , Inibidores do Citocromo P-450 CYP2E1/síntese química , Inibidores do Citocromo P-450 CYP2E1/farmacologia , Fígado Gorduroso Alcoólico/metabolismo , Fígado Gorduroso Alcoólico/patologia , Feminino , Células Hep G2 , Humanos , Lipoproteínas VLDL/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Índice de Gravidade de Doença , Triglicerídeos/sangue , Ácido Ursodesoxicólico/análise
19.
Food Chem ; 332: 127405, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32603919

RESUMO

The two-phase technology for olive oil extraction generates large amounts of patè olive cake (POC), a by-product that is rich in bioactive health-promoting compounds. Here, response surface methodology (RSM) was used to maximize supercritical-CO2 oil extraction from POC, while minimizing operative temperature, pressure and time. Under the optimal parameters (40.2 °C, 43.8 MPa and time 30 min), the oil yield was 14.5 g·100 g-1 dw (~65% of the total oil content of the freeze-dried POC matrix), as predicted by RSM. Compared with freeze-dried POC, the oil contained more phytosterols (13-fold), tocopherols (6-fold) and squalene (8-fold) and was a good source of pentacyclic triterpenes. When the biological effects of POC oil intake (20-40 µL·die-1) were evaluated in the livers of BALB/c mice, no significant influence on redox homeostasis was observed. Notably, a decline in liver triglycerides alongside increased activities of NAD(P)H:Quinone Oxidoreductase 1, Carnitine Palmitoyl-CoA Transferase and mitochondrial respiratory complexes suggested a potential beneficial effect on liver fatty acid oxidation.


Assuntos
Cromatografia com Fluido Supercrítico/métodos , Azeite de Oliva/química , Animais , Dióxido de Carbono/química , Peroxidação de Lipídeos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Olea/metabolismo , Azeite de Oliva/isolamento & purificação , Azeite de Oliva/farmacologia , Fitosteróis/química , Fitosteróis/isolamento & purificação , Propriedades de Superfície , Temperatura , Tocoferóis/química , Tocoferóis/isolamento & purificação , Triglicerídeos/metabolismo
20.
Adv Exp Med Biol ; 1207: 237-264, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32671753

RESUMO

Autophagy is an evolutionarily conserved process in eukaryotes that processes the turnover of intracellular substances. Atherosclerosis is a disease caused by multiple factors, it mainly occurs on the walls of large and medium blood vessels and atherosclerotic plaques form in the intima of the blood vessels. Hyperlipidemia is considered to be a very dangerous factor leading to cardiovascular and cerebrovascular diseases, especially atherosclerosis. This chapter mainly introduces the key role of autophagy in hyperlipidemia and atherosclerosis, that is, impaired lipophagy affects the degradation of triacylglycerol, cholesterol, etc., leading to hyperlipidemia in atherosclerosis. In patients, excessive levels of autophagy accelerate the rupture of atherosclerotic plaque. This chapter also describes the advances in the treatment of atherosclerosis and hyperlipidemia by targeted autophagy.


Assuntos
Aterosclerose , Autofagia , Hiperlipidemias , Colesterol , Humanos , Placa Aterosclerótica , Triglicerídeos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA