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1.
Acta Cir Bras ; 35(4): e202000403, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32578723

RESUMO

PURPOSE: To collect data capable of pointing out the effects of the ultracavitation treatment on the liver of rabbits after adipose tissue application, by means of histological analyses of the liver and hematological and biochemical exams. METHODS: This is an experimental study with 12 albino rabbits as sample, which were divided into 3 groups and submitted to a hypercaloric diet for one month. Subsequently, subjects underwent UCV treatment: 3 minutes, 30 W, continuous mode at 100%, every 2 ERAS = 441.02 J/cm2, intensity of 10w/cm2. They were then euthanized and underwent biopsy after 24 hours. RESULTS: After 48 hours from the ultracavitation treatment, the animals' livers presented greater amount of fat infiltration if compared to the amount presented 96 hours after the treatment. However, laboratory tests showed no alterations. Values were maintained within normal parameters of cholesterol, triglycerides, liver enzymes, hemoglobin and hematocrit levels. CONCLUSIONS: This study has identified that infiltrates may appear on livers after the treatment, despite high hematological and biochemical tests results. The fat infiltrates reduction 96 h after treatment suggests lower risks to animal health, if the period between applications is respected.


Assuntos
Tecido Adiposo/patologia , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Lipodistrofia/patologia , Lipodistrofia/terapia , Fígado/patologia , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Colesterol/sangue , Feminino , Hematócrito , Hemoglobinas/análise , Ablação por Ultrassom Focalizado de Alta Intensidade/efeitos adversos , Lipodistrofia/sangue , Masculino , Coelhos , Valores de Referência , Reprodutibilidade dos Testes , Fatores de Risco , Resultado do Tratamento , Triglicerídeos/sangue
2.
J Clin Lipidol ; 14(3): 297-304, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32430154

RESUMO

BACKGROUND: Many patients with coronavirus disease 2019 (COVID-19) suffer multiple organ dysfunctions. However, whether patients develop dyslipidemia is unknown. OBJECTIVE: In this study, we aimed to investigate the pathological alterations of low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and total cholesterol (TC) in COVID-19 patients and their relationships with the disease severity. METHODS: A retrospective study was performed to examine serum levels of LDL-c, HDL-c, and TC on 597 COVID-19 patients (mild: 394; severe, 171; critical: 32) who were hospitalized in our center between February 1 and March 3, 2020. Age- and gender-matched normal subjects (n = 50) who had routine laboratory lipid tests between October 1 and November 1, 2019 in our center were included as the control group. RESULTS: LDL-c and TC levels were significantly lower in COVID-19 patients as compared with normal subjects (P < .001). There were significant and gradual decreases in levels of LDL-c (median (IQR) in mg/dL, mild: 91 (76, 104); severe: 86 (69, 102); critical: 69 (48, 81); P < .02) and TC (mild: 173 (148, 203); severe: 167 (138, 197); critical: 125 (95, 162); P < .05) across all three groups. HDL-c levels only decreased significantly in critical cases as compared with levels in mild and severe cases. LDL-c and TC levels inversely correlated with C-reactive protein and interleukin-6, and positively correlated with the number of lymphocytes in patients. CONCLUSIONS: Development of hypolipidemia begins in patients with mild symptoms. It progressively becomes worse in an association with the disease severity.


Assuntos
Betacoronavirus , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Infecções por Coronavirus/sangue , Pneumonia Viral/sangue , Índice de Gravidade de Doença , Idoso , Colesterol/sangue , Infecções por Coronavirus/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Estudos Retrospectivos
3.
Nano Lett ; 20(6): 4543-4549, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32375002

RESUMO

Lipid nanoparticle (LNP) packaged mRNA vaccines have been deployed against infectious diseases such as COVID-19, yet their structural features remain unclear. Cholesterol, a major constituent within LNPs, contributes to their morphology that influences gene delivery. Herein, we examine the structure of LNPs containing cholesterol derivatives using electron microscopy, differential scanning calorimetry, and membrane fluidity assays. LNPs formulated with C24 alkyl derivatives of cholesterol show a polymorphic shape and various degrees of multilamellarity and lipid partitioning, likely due to phase separation. The addition of methyl and ethyl groups to the C24 alkyl tail of the cholesterol backbone induces multilamellarity (>50% increase compared to cholesterol), while the addition of a double bond induces lipid partitioning (>90% increase compared to cholesterol). LNPs with multilamellar and faceted structures, as well as a lamellar lipid phase, showed higher gene transfection. Unraveling the structure of mRNA-LNPs can enable their rational design toward enhanced gene delivery.


Assuntos
Colesterol/análogos & derivados , Infecções por Coronavirus/prevenção & controle , Portadores de Fármacos/química , Nanopartículas/química , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , RNA Mensageiro/administração & dosagem , Vacinas Virais/administração & dosagem , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/genética , Técnicas de Transferência de Genes , Células HeLa , Humanos , Lipídeos/química , Nanopartículas/ultraestrutura , Transição de Fase , Fitosteróis/química , RNA Mensageiro/genética , Transfecção , Vacinas Virais/genética
4.
Gene ; 749: 144720, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32360840

RESUMO

AIMS: The purpose of present study was to examine the correlations of LDL (LDLR) and HDL (SR-B1) receptors with lipoproteins, miR-199a-5p, miR-199b-5p, miR-455-5p in the malignant and benign breast tumors. METHODS: Total cholesterol-rich-lipoproteins and the receptors were determined using enzymatic-homogeneous and ELISA methods. The expression levels of miRNAs were detected by qRT-PCR. RESULTS: Receptor expressions and lipoproteins concentration were significantly higher in the malignant tumors (p < 0.05). Positive correlation was found for LDLR with Ki67% and Her2+. HDL-C content of TNBC tumors was higher than those of Non-TNBC (p < 0.05). The expression level of miR-199a-5p was found to be downregulated significantly in the malignant tumors of <2 cm, TNBC, HER2- or stage3. The expression of miR-199b-5p was downregulated in the malignant tumors and was negatively associated with TNBC, stage and Her2+. The expression of miR-455-5p was significantly correlated with Her2- (p < 0.05). A positive correlation was observed for SR-B1 or LDLR with HDL-C or LDL-C and also for SR-B1 with LDLR, although a reverse association was detected for the expression of miR-199b-5p with LDLR in the malignant tumors (p < 0.05). No significant correlations were found for miR-199a-5p or miR-455-5p with LDLR or SR-B1 expressions and also for LDL-C and SR-B1 with clinicopathological features (p ≥ 0.05). CONCLUSIONS: Mechanisms potentially involved in the present findings may be due to the lipid internalization and lipoprotein consumption through LDLR and SR-B1 over expression. It is noteworthy that the expression of miR-199b-5p is negatively correlated with LDLR which may suggest it as a suppressor for LDLR expression in the breast cancer.


Assuntos
Neoplasias da Mama/metabolismo , MicroRNAs/metabolismo , Receptores de LDL/metabolismo , Receptores Depuradores Classe B/metabolismo , Adulto , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Colesterol/metabolismo , Feminino , Humanos , Lipoproteínas/metabolismo , Pessoa de Meia-Idade
5.
Med Hypotheses ; 141: 109750, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32388138

RESUMO

Although not widely studied, behavioral host manipulation by various pathogens has been documented. Host manipulation is the process by which a pathogen evolves adaptations to manipulate the behavior of the host to maximize reproduction (Ro) of the pathogen. The most notable example is rabies. When a host is infected with the rabies virus it gets into the host's central nervous system and triggers hyper aggression. The virus is also present in the rabid animal's saliva so being bitten transmits the infection to a new host and the old host is left to eventually die if untreated. Toxoplasmosis is another example. When mice are infected they demonstrate a fearlessness toward cats, thus increasing their chances of being eaten. Toxoplasmosis needs the digestive tract of the feline to survive. Recent studies have shown that exposure to toxoplasmosis in humans (e.g., through cat feces) has also been associated with behavioral changes that are predicted to enhance the spread of the pathogen. Even the common influenza virus has been shown to selectively increase in-person sociality during the 48-hour incubation period, thus producing an obvious vector for transmission. Here we hypothesize that the novel coronavirus, SARS-CoV2, which produces the COVID-19 disease may produce similar host manipulations that maximize its transmission between humans.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/virologia , Interações Hospedeiro-Patógeno , Modelos Biológicos , Pneumonia Viral/virologia , Comportamento Social , Adulto , Animais , Doenças Assintomáticas/psicologia , Betacoronavirus/genética , Betacoronavirus/fisiologia , Evolução Biológica , Cuidadores , Criança , Comportamento Infantil , Pré-Escolar , Colesterol/sangue , Infecções por Coronavirus/transmissão , Coleta de Dados , Feminino , Feto/virologia , Giro do Cíngulo/fisiopatologia , Especificidade de Hospedeiro , Interações Hospedeiro-Patógeno/fisiologia , Humanos , Lactente , Recém-Nascido , Período de Incubação de Doenças Infecciosas , Masculino , Pandemias , Pneumonia Viral/transmissão , Gravidez , Complicações Infecciosas na Gravidez/virologia , Efeitos Tardios da Exposição Pré-Natal
6.
Nature ; 581(7808): 339-343, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32433613

RESUMO

Cholesterol is an essential component of mammalian cell membranes, constituting up to 50% of plasma membrane lipids. By contrast, it accounts for only 5% of lipids in the endoplasmic reticulum (ER)1. The ER enzyme sterol O-acyltransferase 1 (also named acyl-coenzyme A:cholesterol acyltransferase, ACAT1) transfers a long-chain fatty acid to cholesterol to form cholesteryl esters that coalesce into cytosolic lipid droplets. Under conditions of cholesterol overload, ACAT1 maintains the low cholesterol concentration of the ER and thereby has an essential role in cholesterol homeostasis2,3. ACAT1 has also been implicated in Alzheimer's disease4, atherosclerosis5 and cancers6. Here we report a cryo-electron microscopy structure of human ACAT1 in complex with nevanimibe7, an inhibitor that is in clinical trials for the treatment of congenital adrenal hyperplasia. The ACAT1 holoenzyme is a tetramer that consists of two homodimers. Each monomer contains nine transmembrane helices (TMs), six of which (TM4-TM9) form a cavity that accommodates nevanimibe and an endogenous acyl-coenzyme A. This cavity also contains a histidine that has previously been identified as essential for catalytic activity8. Our structural data and biochemical analyses provide a physical model to explain the process of cholesterol esterification, as well as details of the interaction between nevanimibe and ACAT1, which may help to accelerate the development of ACAT1 inhibitors to treat related diseases.


Assuntos
Microscopia Crioeletrônica , Esterol O-Aciltransferase/química , Esterol O-Aciltransferase/ultraestrutura , Colesterol/química , Colesterol/metabolismo , Histidina/química , Histidina/metabolismo , Holoenzimas/química , Holoenzimas/ultraestrutura , Humanos , Ligantes , Modelos Moleculares , Multimerização Proteica , Eletricidade Estática
7.
Medicine (Baltimore) ; 99(20): e20202, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443343

RESUMO

AIM: Maintenance hemodialysis (MHD) frequency is associated with survival and complication rates. Achieving the optimal balance between healthcare, quality of life (QOL), and medical costs is challenging. We compared complications, inflammatory status, nutritional status, and QOL between patients with different MHD frequencies. MATERIAL AND METHODS: This was a multicenter randomized trial of patients treated between May 2011 and August 2017 at 3 tertiary hospitals in Wenzhou. Patients were grouped according to their treatment schedule over 1 year: twice-weekly or 3-times-weekly. Complications, biochemistry parameters, and QOL (KDQOL-SFTM 1.3 scale) were assessed. RESULTS: One hundred forty patients were included aged 29 to 68 years (mean age, 50.9 ±â€Š4.3 years). There were no significant differences in infection, heart failure, or cerebral hemorrhage complications between the 2 groups (P = .664). Pre-dialysis hemoglobin, high-sensitivity C-reactive protein, serum albumin, total cholesterol, triglyceride, calcium, phosphate, parathyroid hormone, and ejection fraction were similar in both groups (P > .05). After 1 year of MHD, both groups exhibited significant improvements in these parameters (all P < .05) with no significant differences between groups. Serum creatinine, blood urea nitrogen (BUN), and weekly standard hemodialysis treatment adequacy did not improve after treatment (all P > .05), although a difference in BUN was observed between the 2 groups (P < .001). QOL was superior in the twice-weekly group than in the 3-times-weekly group (all P < .05), except for social support, which was slightly better in the 3-times-weekly group than in the twice-weekly group. CONCLUSIONS: Twice- and 3-times-weekly MHD resulted in comparable inflammatory and nutritional clinical outcomes and adverse events. QOL was better for the twice-weekly schedule. Even for patients with economic constraints, twice- or 3-times-weekly MHD should be selected with caution after consideration of BUN levels at baseline.


Assuntos
Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , Diálise Renal/tendências , Nitrogênio da Ureia Sanguínea , Proteína C-Reativa/análise , Cálcio/sangue , Hemorragia Cerebral/epidemiologia , China/epidemiologia , Colesterol/sangue , Creatinina/sangue , Feminino , Insuficiência Cardíaca/epidemiologia , Hemoglobinas/análise , Humanos , Infecções/epidemiologia , Inflamação/epidemiologia , Masculino , Pessoa de Meia-Idade , Estado Nutricional/fisiologia , Hormônio Paratireóideo/sangue , Fosfatos/sangue , Qualidade de Vida/psicologia , Diálise Renal/economia , Diálise Renal/psicologia , Albumina Sérica , Volume Sistólico/fisiologia , Triglicerídeos/sangue
9.
Chin J Nat Med ; 18(3): 186-195, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32245588

RESUMO

Alcoholic liver disease (ALD) has become one of the leading causes of death in the world. Berbamine (BM), a natural product mainly derived from Berberis vulgaris L, possesses multiple bioactivities as a traditional medicine. However, the protective effect of BM on ALD remains unknown. In this study, we investigated the effect of BM on ethanol-induced hepatic injury in mice and its underlying mechanism. It was shown that BM at 0.3125-40 µmol·L-1had no effect on macrophages and hepatocytes proliferation. BM at 5-20 µmol·L-1 significantly inhibited lipopolysaccharide (LPS) or acetate-induced IL-1ß and IL-6 mRNA expression in RAW264.7 cells. Moreover, BM treatment significantly inhibited LPS-induced p65 and STAT3 phosphorylation in RAW264.7 cells. Hepatic histopathology analysis showed that inflammatory cells infiltration and lipid accumulation were suppressed by 25 and 50 mg·kg-1 BM administration in ethanol-induced hepatic injury mouse model. Meanwhile, BM treatment significantly inhibited serum ALT and AST levels in ethanol-fed mice. Oil red O staining results showed that BM administration ameliorated hepatic lipid accumulation in ethanol-fed mice. Preventions of ethanol-induced hepatic injury by BM were reflected by markedly decreased serum and hepatic triglyceride (TG) and total cholesterol (TC) contents. Real-time PCR results showed that BM treatment significantly inhibited pro-inflammatory cytokines mRNA expression in ethanol-fed mouse liver. Remarkably, the mechanism of action of BM was related to the reduction of ethanol-induced NF-κB and STAT3 phosphorylation levels in liver. In addition, BM treatment significantly inhibited ERK phosphorylation but not JNK and p38 of MAPK pathway. Taken together, our results demonstrate a beneficial effect of BM on ethanol-induced liver injury via a mechanism associated with inactivation of NF-κB, STAT3 and ERK pathway, which gives insight into the further evaluation of the therapeutic potential of BM for ALD.


Assuntos
Benzilisoquinolinas/farmacologia , Doença Hepática Crônica Induzida por Substâncias e Drogas/tratamento farmacológico , Inflamação/tratamento farmacológico , Fígado/efeitos dos fármacos , Animais , Colesterol/sangue , Citocinas/metabolismo , Etanol/efeitos adversos , Feminino , Hepatócitos/efeitos dos fármacos , Metabolismo dos Lipídeos , Sistema de Sinalização das MAP Quinases , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Células RAW 264.7 , Fator de Transcrição STAT3/metabolismo , Triglicerídeos/sangue
10.
Anticancer Res ; 40(4): 1833-1841, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234871

RESUMO

BACKGROUND/AIM: Time-restricted feeding (TRF) during the dark phase of the day restores metabolic homeostasis in mice. MATERIALS AND METHODS: We performed untargeted metabolomic analysis on plasma from mice subjected to TRF that attenuates high-fat diet-enhanced spontaneous metastasis of Lewis lung carcinoma (LLC). RESULTS: Twenty-four of 152 identified metabolites differed among the four dietary groups (non-LLC-bearing mice fed the AIN93G diet and LLC-bearing mice fed the AIN93G, the high-fat diet (HFD), or TRF of the HFD). Component 1 of sparse partial least squares-discriminant analysis showed a clear separation between non-LLC-bearing and LLC-bearing mice. Major metabolites responsible for the changes were elevations in α-tocopherol, docosahexaenoic acid, cholesterol, dihydrocholestrol, isoleucine, leucine, and phenylalanine and decreases in lactic acid and pyruvic acid in LLC-bearing mice particularly those fed the HFD. Time-restricted feeding shifted the metabolic profile of LLC-bearing mice towards that of non-LLC-bearing controls. CONCLUSION: Time-restricted feeding improves metabolic profile of LLC-bearing mice.


Assuntos
Carcinoma Pulmonar de Lewis/sangue , Jejum/sangue , Metabolômica , Animais , Carcinoma Pulmonar de Lewis/dietoterapia , Colestanol/sangue , Colesterol/sangue , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Ácidos Docosa-Hexaenoicos/sangue , Jejum/fisiologia , Humanos , Insulina/sangue , Isoleucina/sangue , Ácido Láctico/sangue , Leucina/sangue , Camundongos , Metástase Neoplásica , Fenilalanina/sangue , Ácido Pirúvico/sangue , alfa-Tocoferol/sangue
11.
Nutrients ; 12(4)2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32252374

RESUMO

Low-carbohydrate diets (LCDs) often differ in their diet composition, which may lead to conflicting results between randomized controlled trials. Therefore, we aimed to compare the effects of different degrees of carbohydrate (CHO) restriction on cardiometabolic risk markers in humans. The experimental LCDs of 37 human trials were classified as (1) moderate-low CHO diets (<45-40 E%, n = 13), (2) low CHO diets (<40-30 E%, n = 16), and (3) very-low CHO diets (<30-3 E%; n = 8). Summary estimates of weighted mean differences (WMDs) in selected risk markers were calculated using random-effect meta-analyses. Differences between the LCD groups were assessed with univariate meta-regression analyses. Overall, the LCDs resulted in significant weight loss, reduced diastolic blood pressure BP, and increased total cholesterol and high-density lipoprotein cholesterol (HDL-C), without significant differences between the three LCD groups. Higher low-density lipoprotein cholesterol (LDL-C) concentrations were found with the very-low CHO diets compared to the moderate-low CHO diets. Decreases in triacylglycerol (TAG) concentrations were more pronounced with the low and very-low CHO diets, compared to the moderate-low CHO diets. Substitution of CHO by mainly saturated fatty acids (SFAs) increased total cholesterol, LDL-C, and HDL-C concentrations. Except for LDL-C and TAGs, effects were not related to the degree of CHO restriction. Potential effects of nutrient exchanges should be considered when following LCDs.


Assuntos
Colesterol/metabolismo , Dieta com Restrição de Carboidratos , Carboidratos da Dieta/administração & dosagem , Carboidratos da Dieta/metabolismo , Triglicerídeos/metabolismo , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Humanos
12.
PLoS One ; 15(4): e0230769, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32259832

RESUMO

Bottlenose dolphins (Tursiops truncatus) are long-lived mammals that can develop chronic aging-associated conditions similar to humans, including metabolic syndrome. Initial studies suggest that these conditions may be attenuated in dolphins using a modified fish diet. Serum metabolomics, fatty acid panels, and blood-based health indices were compared between 20 dolphins on a modified, 50% wild-type diet (50% mullet, 25% capelin, and 25% squid and/or herring) and 10 dolphins on a baseline diet (75% capelin and 25% squid and/or herring). Blood samples were collected at Months 0, 1, 3 and 6. Dolphins on the modified diet had lower insulin (7.5 ± 4.0 and 14.8 ± 14.0 µIU/ml, P = 0.039), lower cholesterol (160 ± 26 and 186 ± 24 mg/dl, P = 0.015) and higher hematocrit (46 ± 3 and 44 ± 3%, P = 0.043) by Month 1 compared to controls. Dolphins with anemia (hemoglobin ≤ 12.5 g/dl, n = 6) or low-normal hemoglobin (12.5-13.5 g/dl, n = 3) before placed on the modified diet had normal hemoglobin concentrations (> 13.5 g/dl) by Month 3. The modified diet caused a significant shift in the metabolome, which included 664 known metabolites. Thirty prioritized metabolites at Months 1 and 3 were 100% predictive of dolphins on the modified diet. Among 25 prioritized lipids, 10 (40%) contained odd-chain saturated fatty acids (OCFAs); C15:0 was the highest-prioritized OCFA. Increased dietary intake of C15:0 (from 1.3 ± 0.4 to 4.5 ± 1.1 g/day) resulted in increased erythrocyte C15:0 concentrations (from 1.5 ± 0.3 to 5.8 ± 0.8 µg/ml, P < 0.0001), which independently predicted raised hemoglobin. Further, increasing age was associated with declining serum C15:0 (R2 = 0.14, P = 0.04). While higher circulating OCFAs have been previously associated with lower risks of cardiometabolic diseases in humans, further studies are warranted to assess potential active roles of OCFAs, including C15:0, in attenuating anemia.


Assuntos
Anemia/etiologia , Anemia/metabolismo , Golfinho Nariz-de-Garrafa/sangue , Golfinho Nariz-de-Garrafa/metabolismo , Ácidos Graxos/metabolismo , Peixes/sangue , Peixes/metabolismo , Metaboloma/fisiologia , Animais , Colesterol/metabolismo , Dieta/métodos , Feminino , Masculino , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo
13.
Phys Rev Lett ; 124(10): 108102, 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32216409

RESUMO

Lipid rafts serve as anchoring platforms for membrane proteins. Thus far they escaped direct observation by light microscopy due to their small size. Here we used differently colored dyes as reporters for the registration of both ordered and disordered lipids from the two leaves of a freestanding bilayer. Photoswitchable lipids dissolved or reformed the domains. Measurements of domain mobility indicated the presence of 120 nm wide ordered and 40 nm wide disordered domains. These sizes are in line with the predicted roles of line tension and membrane undulation as driving forces for alignment.


Assuntos
Lipídeos de Membrana/administração & dosagem , Microdomínios da Membrana/química , Colesterol/química , Colesterol/metabolismo , Diglicerídeos/química , Diglicerídeos/metabolismo , Lipídeos de Membrana/química , Lipídeos de Membrana/metabolismo , Microdomínios da Membrana/metabolismo , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Microscopia Confocal/métodos , Modelos Químicos , Fosfatidilcolinas/química , Fosfatidilcolinas/metabolismo , Espectrometria de Fluorescência/métodos
14.
Subcell Biochem ; 94: 399-420, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32189309

RESUMO

High-density lipoprotein (HDL) and its main protein component apolipoprotein (apo)A-I, play an important role in cholesterol homeostasis. It has been demonstrated that HDLs comprise of a very heterogeneous group of particles, not only regarding size but also composition. HDL's best described function is its role in the reverse cholesterol transport, where lipid-free apoA-I or small HDLs can accept and take up cholesterol from peripheral cells and subsequently transport this to the liver for excretion. However, several other functions have also been described, like anti-oxidant, anti-inflammatory and anti-thrombotic effects. In this article, the general features, synthesis and metabolism of apoA-I and HDLs will be discussed. Additionally, an overview of HDL functions will be given, especially in the context of some major pathologies like cardiovascular disease, cancer and diabetes mellitus. Finally, the therapeutic potential of raising HDL will be discussed, focussing on the difficulties of the past and the promises of the future.


Assuntos
Apolipoproteína A-I/metabolismo , Lipoproteínas HDL/metabolismo , Apolipoproteína A-I/biossíntese , Doenças Cardiovasculares/metabolismo , Colesterol/metabolismo , Diabetes Mellitus/metabolismo , Humanos , Neoplasias/metabolismo
15.
Subcell Biochem ; 94: 421-436, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32189310

RESUMO

As normal constituents of blood serum, the Serum Amyloid A (SAA) proteins are small (104 amino acids in humans) and remarkably well-conserved in mammalian evolution. They are synthesized prominently, but not exclusively, in the liver. Fragments of SAA can associate into insoluble fibrils (called "amyloid") characteristic of "secondary" amyloid disease in which they can interrupt normal physiology and lead to organ failure. SAA proteins comprise a family of molecules, two members of which (SAA1 and SAA2) are (along with C-reactive protein, CRP) the most prominent members of the acute phase response (APR) during which their serum levels rise dramatically after trauma, infection and other stimuli. Biologic function (s) of SAA are unresolved but features are consistent with a prominent role in primordial host defense (including the APR ). SAA proteins are lipophilic and contribute to high density lipoproteins (HDL) and cholesterol transport. SAA proteins interact with specific receptors and have been implicated in tissue remodeling through metalloproteinases, local tissue changes in atherosclerosis, cancer metastasis, lung inflammation, maternal-fetal health and intestinal physiology. Molecular details of some of these are emerging.


Assuntos
Proteína Amiloide A Sérica , Reação de Fase Aguda , Amiloide/química , Amiloide/metabolismo , Animais , Colesterol/metabolismo , Doença , Humanos , Lipoproteínas HDL/metabolismo , Fígado/metabolismo , Proteína Amiloide A Sérica/química , Proteína Amiloide A Sérica/metabolismo
16.
Clin Chim Acta ; 505: 176-182, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32156606

RESUMO

BACKGROUND: Recent studies revealed that several genetic polymorphisms of haptoglobin gene (HP) and the haptoglobin-related protein gene (HPR) associated not only with haptoglobin (HP) but total, non-HDL, and/or LDL cholesterol concentrations in various populations. METHODS: Association between serum HP concentrations and polymorphisms of HP and the HPR gene, or anthropometric and metabolic factors were examined in Mongolian participants (n = 927) using linear regression analyses. RESULTS: The association of HP and HPR polymorphisms with serum HP concentration but not serum lipids concentrations was observed. However, subgroup analysis revealed that the association of HP and HPR polymorphisms with serum HP concentration was weakened in subgroup of obese (BMI ≥ 30) subjects and positive correlations between serum HP and non-HDL cholesterol, HDL cholesterol or triglyceride concentrations were observed in the obese subjects as compared with in subgroups of normal weight (BMI < 25) and overweight (25 ≤ BMI < 30) subjects. CONCLUSION: The degree of obesity strongly affects the relationships between serum HP concentrations and several genetic, anthropometric and metabolic factors. These results suggested that we need to take into account the degree of obesity when considering the HP polymorphisms as predictive markers for clinical states.


Assuntos
Colesterol/sangue , Haptoglobinas/análise , Obesidade/sangue , Obesidade/epidemiologia , Triglicerídeos/sangue , Adulto , Antígenos de Neoplasias/sangue , Antígenos de Neoplasias/genética , Grupo com Ancestrais do Continente Asiático , HDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Haptoglobinas/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mongólia/epidemiologia , Sobrepeso/sangue , Sobrepeso/genética , Polimorfismo Genético/genética , Polimorfismo de Nucleotídeo Único/genética
17.
Rev Assoc Med Bras (1992) ; 66(1): 67-73, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32130384

RESUMO

OBJECTIVES: Individuals living with HIV seem to be more prone to changes in the redistribution of body fat, characterized as lipodystrophy, which may occur in conjunction with metabolic diseases. In the present study, such impacts were assessed in adults with and without HIV and associated with the time of virus diagnosis and treatment with antiretroviral. METHODS: A cross-sectional study with 123 adults, in which 87 had HIV and 36 without HIV, of both sexes, in outpatient follow-up at the Specialized Care Service (SAE) in Macaé-RJ. The following were made: 1) Alteration in body fat distribution, measured by anthropometric parameters and self-reported lipodystrophy; 2) Biochemical profile; 3) Association between HIV diagnosis time and antiretroviral treatment. RESULTS: 54.47% (n = 67) males, 45.52% (n = 56) females, mean age 37 years. Of these 87 were people living with HIV, 29% (n = 25) had self-reported lipodystrophy, mean time of virus infection, and antiretroviral treatment (5.80 ± 4.56 and 5.14 ± 3.82 years), respectively. Patients with self-reported lipodystrophy had a greater change in body fat distribution between 3-6 years of HIV diagnosis and a negative cholesterol profile. The antiretroviral treatment time influenced total cholesterol and triglycerides, even for patients without self-reported lipodystrophy, with a further nine years under treatment. CONCLUSION: In this study, the negative cholesterol profile was mainly related to antiretroviral treatment time, even for patients without self-reported lipodystrophy, and changes in body fat distribution, measured by anthropometry, was especially associated with time for HIV infection in those with lipodystrophy self-reported.


Assuntos
Antirretrovirais/uso terapêutico , Distribuição da Gordura Corporal , Infecções por HIV/tratamento farmacológico , Síndrome de Lipodistrofia Associada ao HIV/epidemiologia , Síndrome de Lipodistrofia Associada ao HIV/fisiopatologia , Tecido Adiposo/fisiopatologia , Adolescente , Adulto , Análise de Variância , Terapia Antirretroviral de Alta Atividade , Índice de Massa Corporal , Brasil/epidemiologia , Colesterol/sangue , Estudos Transversais , Feminino , Infecções por HIV/sangue , Síndrome de Lipodistrofia Associada ao HIV/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Autorrelato , Fatores Sexuais , Fatores de Tempo , Triglicerídeos/sangue , Adulto Jovem
18.
Nat Commun ; 11(1): 1128, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111832

RESUMO

The sterol-regulatory element binding proteins (SREBP) are central transcriptional regulators of lipid metabolism. Using haploid genetic screens we identify the SREBP Regulating Gene (SPRING/C12ORF49) as a determinant of the SREBP pathway. SPRING is a glycosylated Golgi-resident membrane protein and its ablation in Hap1 cells, Hepa1-6 hepatoma cells, and primary murine hepatocytes reduces SREBP signaling. In mice, Spring deletion is embryonic lethal yet silencing of hepatic Spring expression also attenuates the SREBP response. Mechanistically, attenuated SREBP signaling in SPRINGKO cells results from reduced SREBP cleavage-activating protein (SCAP) and its mislocalization to the Golgi irrespective of the cellular sterol status. Consistent with limited functional SCAP in SPRINGKO cells, reintroducing SCAP restores SREBP-dependent signaling and function. Moreover, in line with the role of SREBP in tumor growth, a wide range of tumor cell lines display dependency on SPRING expression. In conclusion, we identify SPRING as a previously unrecognized modulator of SREBP signaling.


Assuntos
Colesterol/metabolismo , Glicoproteínas de Membrana/metabolismo , Transdução de Sinais , Proteínas de Ligação a Elemento Regulador de Esterol/metabolismo , Animais , Linhagem Celular , Desenvolvimento Embrionário/genética , Retículo Endoplasmático/metabolismo , Expressão Gênica , Complexo de Golgi/metabolismo , Haploidia , Hepatócitos/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Glicoproteínas de Membrana/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas de Ligação a Elemento Regulador de Esterol/genética
19.
PLoS One ; 15(3): e0219275, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32163417

RESUMO

Pathogenic bacteria often damage tissues by secreting toxins that form pores in cell membranes, and the most common pore-forming toxins are cholesterol-dependent cytolysins. During bacterial infections, glutamine becomes a conditionally essential amino acid, and glutamine is an important nutrient for immune cells. However, the role of glutamine in protecting tissue cells against pore-forming toxins is unclear. Here we tested the hypothesis that glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins. Stromal and epithelial cells were sensitive to damage by the cholesterol-dependent cytolysins, pyolysin and streptolysin O, as determined by leakage of potassium and lactate dehydrogenase from cells, and reduced cell viability. However, glutamine deprivation increased the leakage of lactate dehydrogenase and reduced the viability of cells challenged with cholesterol-dependent cytolysins. Without glutamine, stromal cells challenged with pyolysin leaked lactate dehydrogenase (control vs. pyolysin, 2.6 ± 0.6 vs. 34.4 ± 4.5 AU, n = 12), which was more than three-fold the leakage from cells supplied with 2 mM glutamine (control vs. pyolysin, 2.2 ± 0.3 vs. 9.4 ± 1.0 AU). Glutamine cytoprotection did not depend on glutaminolysis, replenishing the Krebs cycle via succinate, changes in cellular cholesterol, or regulators of cell metabolism (AMPK and mTOR). In conclusion, although the mechanism remains elusive, we found that glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria.


Assuntos
Colesterol/metabolismo , Citoproteção/efeitos dos fármacos , Citotoxinas/toxicidade , Glutamina/farmacologia , Animais , Proteínas de Bactérias/toxicidade , Toxinas Bacterianas/toxicidade , Bovinos , Células HeLa , Proteínas Hemolisinas/toxicidade , Humanos , L-Lactato Desidrogenase/metabolismo , Estreptolisinas/toxicidade , Células Estromais/efeitos dos fármacos
20.
Ann Hematol ; 99(5): 937-945, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32166377

RESUMO

Hydroxyurea (HU) is used as a therapy in sickle cell anemia (SCA). Many studies have established that HU improves patient quality of life by reducing symptoms. However, the effect of HU on erythrocytes is not well-described. We evaluated several parameters related to oxidative stress and total lipid content of erythrocytes in patients with SCA. The patient cohort consisted of 7 SCA patients treated with HU, 17 untreated SCA patients, and 15 healthy subjects. Erythrocytes from patients with SCA displayed increased oxidative stress relative to the control group, including higher thiobarbituric acid reactive substances (TBARS), Fe3+ content, and osmotic fragility, and decreased total cholesterol. We observed that treatment of SCA patients with HU increased Fe3+ content and activity of glutathione peroxidase, and decreased glutathione reductase activity, glutathione levels, total cholesterol, and phospholipid content comaperaded to patients untreated with HU. Thus, HU alters biochemical characteristics of erythrocytes; future studies will determine whether they are beneficial or not.


Assuntos
Anemia Falciforme , Eritrócitos Anormais/metabolismo , Hidroxiureia/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Adulto , Anemia Falciforme/sangue , Anemia Falciforme/tratamento farmacológico , Colesterol/sangue , Feminino , Humanos , Masculino , Fragilidade Osmótica/efeitos dos fármacos , Fosfolipídeos/sangue , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
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