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1.
Int J Mol Sci ; 22(11)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34205975

RESUMO

High-density lipoproteins (HDLs) are a class of blood particles, principally involved in mediating reverse cholesterol transport from peripheral tissue to liver. Omics approaches have identified crucial mediators in the HDL proteomic and lipidomic profile, which are involved in distinct pleiotropic functions. Besides their role as cholesterol transporter, HDLs display anti-inflammatory, anti-apoptotic, anti-thrombotic, and anti-infection properties. Experimental and clinical studies have unveiled significant changes in both HDL serum amount and composition that lead to dysregulated host immune response and endothelial dysfunction in the course of sepsis. Most SARS-Coronavirus-2-infected patients admitted to the intensive care unit showed common features of sepsis disease, such as the overwhelmed systemic inflammatory response and the alterations in serum lipid profile. Despite relevant advances, episodes of mild to moderate acute kidney injury (AKI), occurring during systemic inflammatory diseases, are associated with long-term complications, and high risk of mortality. The multi-faceted relationship of kidney dysfunction with dyslipidemia and inflammation encourages to deepen the clarification of the mechanisms connecting these elements. This review analyzes the multifaced roles of HDL in inflammatory diseases, the renal involvement in lipid metabolism, and the novel potential HDL-based therapies.


Assuntos
COVID-19/patologia , Lipoproteínas HDL/metabolismo , Sepse/patologia , Injúria Renal Aguda/etiologia , COVID-19/complicações , COVID-19/metabolismo , COVID-19/virologia , Colesterol/metabolismo , Proteínas do Sistema Complemento/metabolismo , Humanos , Metabolismo dos Lipídeos , Lipoproteínas HDL/química , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/fisiologia , Sepse/complicações , Sepse/metabolismo , Internalização do Vírus
2.
Int J Mol Sci ; 22(11)2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34199904

RESUMO

Nutrition determines our health, both directly and indirectly. Consumed foods affect the functioning of individual organs as well as entire systems, e.g., the cardiovascular system. There are many different diets, but universal guidelines for proper nutrition are provided in the WHO healthy eating pyramid. According to the latest version, plant products should form the basis of our diet. Many groups of plant compounds with a beneficial effect on human health have been described. Such groups include anthocyanins and iridoids, for which it has been proven that their consumption may lead to, inter alia, antioxidant, cholesterol and lipid-lowering, anti-obesity and anti-diabetic effects. Transcription factors directly affect a number of parameters of cell functions and cellular metabolism. In the context of lipid and cholesterol metabolism, five particularly important transcription factors can be distinguished: liver X receptor (LXR), peroxisome proliferator-activated receptor-α (PPAR-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer binding protein α (C/EBPα) and sterol regulatory element-binding protein 1c (SREBP-1c). Both anthocyanins and iridoids may alter the expression of these transcription factors. The aim of this review is to collect and systematize knowledge about the impact of anthocyanins and iridoids on transcription factors crucial for lipid and cholesterol homeostasis.


Assuntos
Antocianinas/farmacologia , Colesterol/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Homeostase , Iridoides/farmacologia , Lipídeos/análise , Fatores de Transcrição/metabolismo , Animais , Humanos , Metabolismo dos Lipídeos , Fatores de Transcrição/genética
3.
Molecules ; 26(12)2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34205604

RESUMO

Rutin (R) and quercetin (Q) are two widespread dietary flavonoids. Previous studies regarding the plasma cholesterol-lowering activity of R and Q generated inconsistent results. The present study was therefore carried out to investigate the effects of R and Q on cholesterol metabolism in both HepG2 cells and hypercholesterolemia hamsters. Results from HepG2 cell experiments demonstrate that both R and Q decreased cholesterol at doses of 5 and 10 µM. R and Q up-regulated both the mRNA and protein expression of sterol regulatory element binding protein 2 (SREBP2), low-density lipoprotein receptor (LDLR), and liver X receptor alpha (LXRα). The immunofluorescence study revealed that R and Q increased the LDLR expression, while only Q improved LDL-C uptake in HepG2 cells. Results from hypercholesterolemia hamsters fed diets containing R (5.5 g/kg diet) and Q (2.5 g/kg diet) for 8 weeks demonstrate that both R and Q had no effect on plasma total cholesterol. In the liver, only Q reduced cholesterol significantly. The discrepancy between the in vitro and in vivo studies was probably due to a poor bioavailability of flavonoids in the intestine. It was therefore concluded that R and Q were effective in reducing cholesterol in HepG2 cells in vitro, whereas in vivo, the oral administration of the two flavonoids had little effect on plasma cholesterol in hamsters.


Assuntos
Colesterol/sangue , Colesterol/metabolismo , Quercetina/farmacologia , Rutina/farmacologia , Administração Oral , Animais , Linhagem Celular Tumoral , Cricetinae , Flavonoides/farmacologia , Células Hep G2 , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Receptores X do Fígado/metabolismo , Masculino , RNA Mensageiro/metabolismo , Receptores de LDL/sangue , Receptores de LDL/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Triglicerídeos/sangue , Triglicerídeos/metabolismo , Regulação para Cima/efeitos dos fármacos
4.
Molecules ; 26(12)2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34205624

RESUMO

Studies have reported that cholesterol, a molecule found mainly in animals, is also present in some plants and algae. This study aimed to determine whether cholesterol exists in three dehydrated algae species, namely, Pyropia tenera, Saccharina japonica, and Undaria pinnatifida, and in one plant species, namely, Perilla frutescens (four perilla seed oil samples were analyzed). These species were chosen for investigation because they are common ingredients in East Asian cuisine. Gas chromatography-flame ionization detection (GC-FID) analysis found that cholesterol was present in P. tenera (14.6 mg/100 g) and in all four perilla seed oil samples (0.3-0.5 mg/100 g). High-performance liquid chromatography with evaporative light-scattering detection (HPLC-ELSD) also demonstrated that cholesterol was present in P. tenera (14.2 mg/100 g) and allowed the separation of cholesterol from its isomer lathosterol. However, cholesterol could not be detected by HPLC-ELSD in the perilla seed oil samples, most likely because it is only present in trace amounts. Moreover, liquid chromatography-tandem mass spectrometry (LC-MS/MS) confirmed the presence of cholesterol in both P. tenera and perilla seed oil. MRM results further suggested that lathosterol (a precursor of cholesterol) was present in P. tenera.


Assuntos
Perilla frutescens/metabolismo , Petróleo/metabolismo , Óleos Vegetais/metabolismo , Sementes/metabolismo , Ácido alfa-Linoleico/metabolismo , Colesterol/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Espectrometria de Massas em Tandem/métodos
5.
Front Endocrinol (Lausanne) ; 12: 611526, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34248834

RESUMO

Background: It has been reported that dyslipidemia is related to coronavirus-related diseases. Critical patients with coronavirus disease 2019 (COVID-19) who suffered from multiple organ dysfunctions were treated in the intensive care unit (ICU) in Wuhan, China. Whether the lipids profile was associated with the prognosis of COVID-19 in critical patients remained unclear. Methods: A retrospective study was performed in critical patients (N=48) with coronavirus disease 2019 in Leishenshan hospital between February and April 2020 in Wuhan. The parameters including lipid profiles, liver function, and renal function were collected on admission day, 2-3days after the admission, and the day before the achievement of clinical outcome. Results: Albumin value and creatine kinase (ck) value were statistically decreased at 2-3 days after admission compared with those on admission day (P<0.05). Low density lipoprotein (LDL-c), high density lipoprotein (HDL-c), apolipoprotein A (ApoA), and apolipoprotein A (Apo B) levels were statistically decreased after admission (P<0.05). Logistic regression showed that HDL-c level both on admission day and the day before the achievement of clinical outcome were negatively associated with mortality in critical patients with COVID-19. Total cholesterol (TC) level at 2-3days after admission was related to mortality in critical patients with COVID-19. Conclusions: There were lipid metabolic disorders in the critical patients with COVID-19. Lower levels of HDL-c and TC were related to the progression of critical COVID-19.


Assuntos
COVID-19/mortalidade , Dislipidemias/epidemiologia , Mortalidade Hospitalar , Insuficiência de Múltiplos Órgãos/mortalidade , Idoso , Idoso de 80 Anos ou mais , Apolipoproteínas A/sangue , Apolipoproteínas B/sangue , COVID-19/sangue , COVID-19/epidemiologia , China/epidemiologia , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estado Terminal , Dislipidemias/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/epidemiologia , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença
6.
Medicina (Kaunas) ; 57(6)2021 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-34199243

RESUMO

Background and Objectives: The efficacy of hydroxy methyl glutaryl-coenzyme A reductase inhibitors (statins) in reducing the incidence of cardiovascular events pushed the target LDL-cholesterol (LDL-C) levels lower and lower in successive guidelines despite signals regarding potential cognitive side effects. We evaluated the relationship between cognitive impairment and LDL-C levels in elderly ischemic stroke patients. Materials and Methods: 29 ischemic stroke patients aged 65 and above with LDL-C levels ≤70 mg/dL, classified according to the TOAST criteria, underwent detailed neuropsychological testing comprising the MMSE test, Montreal Cognitive Assessment (MoCA) and Addenbrooke's Cognitive Evaluation (ACE-III) test. Their performances were compared to those of 29 age-matched ischemic stroke patients with LDL-Cl levels >71 mg/dL. Results: The MMSE test failed to detect significant cognitive differences between the two groups. The MoCA and ACE-III tests detected impairments in visuo-spatial/executive function, attention, and recall/memory in patients with low LDL-C. A stepwise linear regression model of the ACE-III total scores revealed that LDL-cholesterol levels could contribute to 13.8% of the detected cognitive dysfunction, second in importance only to age, which contributed to 38.8% of the detected impairment. Conclusions: Physicians should be cautious when prescribing statins to elderly people. Hydrophilic ones may be preferred in cognitively impaired patients.


Assuntos
Isquemia Encefálica , Inibidores de Hidroximetilglutaril-CoA Redutases , AVC Isquêmico , Acidente Vascular Cerebral , Idoso , Colesterol , Cognição , Humanos , Neurologistas , Testes Neuropsicológicos
7.
Int J Mol Sci ; 22(11)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34206021

RESUMO

Apolipoprotein A-I (ApoA-I) is the major protein of high density lipoprotein (HDL) particles and has a crucial role in reverse cholesterol transport (RCT). It has been postulated that elevating production of de novo ApoA-I might translate into the formation of new functional HDL particles that could lower cardiovascular disease (CVD) risk via RCT. During inflammation, serum ApoA-I concentrations are reduced, which contributes to the development of dysfunctional HDL particles as Serum Amyloid A (SAA) overtakes the position of ApoA-I within the HDL particles. Therefore, instead of elevating serum HDL cholesterol concentrations, rescuing lower serum ApoA-I concentrations could be beneficial in both normal and inflamed conditions. Several nutritional compounds, amongst others short chain fatty acids (SCFAs), have shown their capacity to modulate hepatic lipoprotein metabolism. In this review we provide an overview of HDL and more specific ApoA-I metabolism, SCFAs physiology and the current knowledge regarding the influence of SCFAs on ApoA-I expression and synthesis in human liver cells. We conclude that the current evidence regarding the effect of SCFAs on ApoA-I transcription and secretion is promising, however there is a need to investigate which dietary fibres could lead to increased SCFAs formation and consequent elevated ApoA-I concentrations.


Assuntos
Apolipoproteína A-I/genética , Ácidos Graxos Voláteis/metabolismo , Inflamação/genética , Fígado/metabolismo , Apolipoproteína A-I/metabolismo , Colesterol/genética , Colesterol/metabolismo , Ácidos Graxos Voláteis/genética , Humanos , Inflamação/metabolismo , Inflamação/patologia , Proteína Amiloide A Sérica/genética , Proteína Amiloide A Sérica/metabolismo
8.
Cent Eur J Public Health ; 29(2): 117-121, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34245551

RESUMO

OBJECTIVES: There has been insufficient evidence for a quantitative recommendation for dietary cholesterol, therefore, we aim to investigate the optimal cholesterol intake related to a lower all-cause mortality risk. METHODS: The National Health and Nutrition Examination Survey (NHANES) is a large population survey to investigate public health in the United States. We analysed data from 1999-2002 linked with mortality data obtained through 2006. Cox proportional hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated to assess risks for all-cause mortality associated with cholesterol intake. RESULTS: A total of 7,728 participants were analysed in the present study, and 519 assumed death events. Compared with the third quartile (216-373 mg/day) of cholesterol intake, the risks of mortality increased in both the first two and the last quartiles (quartile 1: HR 1.53, 95% CI 1.16-2.00; quartile 2: HR 1.22, 95% CI 0.94-1.60; quartile 4: HR 1.39, 95% CI 1.05-1.83). The association between cholesterol intake and the risk of all-cause mortality followed a U-shaped curve, with the cholesterol intake associated with the lowest mortality being 328 mg/day. CONCLUSIONS: The present study suggests an optimal cholesterol intake for lowering the all-cause mortality risk.


Assuntos
Doenças Cardiovasculares , Colesterol , Humanos , Mortalidade , Inquéritos Nutricionais , Modelos de Riscos Proporcionais , Fatores de Risco , Estados Unidos/epidemiologia
9.
Molecules ; 26(11)2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34198955

RESUMO

Hyaluronic acid (HA) is one of the most used biopolymers in the development of drug delivery systems, due to its biocompatibility, biodegradability, non-immunogenicity and intrinsic-targeting properties. HA specifically binds to CD44; this property combined to the EPR effect could provide an option for reinforced active tumor targeting by nanocarriers, improving drug uptake by the cancer cells via the HA-CD44 receptor-mediated endocytosis pathway. Moreover, HA can be easily chemically modified to tailor its physico-chemical properties in view of specific applications. The derivatization with cholesterol confers to HA an amphiphilic character, and then the ability of anchoring to niosomes. HA-Chol was then used to coat Span® or Tween® niosomes providing them with an intrinsic targeting shell. The nanocarrier physico-chemical properties were analyzed in terms of hydrodynamic diameter, ζ-potential, and bilayer structural features to evaluate the difference between naked and HA-coated niosomes. Niosomes stability was evaluated over time and in bovine serum. Moreover, interaction properties of HA-coated nanovesicles with model membranes, namely liposomes, were studied, to obtain insights on their interaction behavior with biological membranes in future experiments. The obtained coated systems showed good chemical physical features and represent a good opportunity to carry out active targeting strategies.


Assuntos
Materiais Biomiméticos/química , Colesterol/química , Receptores de Hialuronatos/metabolismo , Ácido Hialurônico/farmacologia , Animais , Bovinos , Membrana Celular , Sistemas de Liberação de Medicamentos , Estabilidade de Medicamentos , Ácido Hialurônico/síntese química , Ácido Hialurônico/química , Lipossomos , Nanoestruturas , Tamanho da Partícula , Soro/química
10.
Int J Mol Sci ; 22(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207150

RESUMO

P2X7 receptors (P2X7) are cationic channels involved in many diseases. Following their activation by extracellular ATP, distinct signaling pathways are triggered, which lead to various physiological responses such as the secretion of pro-inflammatory cytokines or the modulation of cell death. P2X7 also exhibit unique behaviors, such as "macropore" formation, which corresponds to enhanced large molecule cell membrane permeability and current facilitation, which is caused by prolonged activation. These two phenomena have often been confounded but, thus far, no clear mechanisms have been resolved. Here, by combining different approaches including whole-cell and single-channel recordings, pharmacological and biochemical assays, CRISPR/Cas9 technology and cell imaging, we provide evidence that current facilitation and macropore formation involve functional complexes comprised of P2X7 and TMEM16, a family of Ca2+-activated ion channel/scramblases. We found that current facilitation results in an increase of functional complex-embedded P2X7 open probability, a result that is recapitulated by plasma membrane cholesterol depletion. We further show that macropore formation entails two distinct large molecule permeation components, one of which requires functional complexes featuring TMEM16F subtype, the other likely being direct permeation through the P2X7 pore itself. Such functional complexes can be considered to represent a regulatory hub that may orchestrate distinct P2X7 functionalities.


Assuntos
Anoctaminas/metabolismo , Receptores Purinérgicos P2X7/metabolismo , Trifosfato de Adenosina/metabolismo , Algoritmos , Animais , Anoctaminas/química , Sistemas CRISPR-Cas , Membrana Celular/metabolismo , Permeabilidade da Membrana Celular , Colesterol/metabolismo , Células HEK293 , Humanos , Imuno-Histoquímica , Modelos Biológicos , Oócitos , Receptores Purinérgicos P2X7/química
11.
Int J Mol Sci ; 22(13)2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34281263

RESUMO

Cholesterol is a foundational molecule of biology. There is a long-standing interest in understanding how cholesterol metabolism is intertwined with cancer biology. In this review, we focus on the known connections between lung cancer and molecules mediating cholesterol efflux. A major take-home lesson is that the roles of many cholesterol efflux factors remain underexplored. It is our hope that this article would motivate others to investigate how cholesterol efflux factors contribute to lung cancer biology.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Colesterol/metabolismo , Neoplasias Pulmonares/metabolismo , Transportador 1 de Cassete de Ligação de ATP/genética , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Transportadores de Cassetes de Ligação de ATP/genética , Animais , Apolipoproteína A-I/genética , Apolipoproteína A-I/metabolismo , Transporte Biológico Ativo , Humanos , Proteínas Relacionadas a Receptor de LDL/genética , Proteínas Relacionadas a Receptor de LDL/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , MicroRNAs/genética , MicroRNAs/metabolismo , Modelos Biológicos
12.
Medicina (Kaunas) ; 57(6)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34205836

RESUMO

Background and Objectives: It is known that neutrophils are involved in the pro-inflammatory processes and thus, can have a great impact on the pathophysiology of heart failure (HF). Moreover, hypercholesterolemia heightens neutrophil production, thereby accelerating cardiovascular inflammation. However, there is a lack of information about the relation of low inflammation to the state of stress, hypercholesterolemia, and pro-thrombotic statement in patients with chronic HF. Therefore, we aimed to determine whether platelet, cholesterol and cortisol levels differ in a different inflammatory condition groups according to the neutrophil count in patients diagnosed with CHF with reduced ejection fraction (CHFrEF), and whether there is a correlation between those readings. Materials and Methods: The average of neutrophil count was 4.37 × 109 L; therefore, 180 patients were separated into two groups: one with relatively a higher inflammatory environment (neutrophil count ≥ 4.37 × 109 L (n = 97)) and one with a relatively lower inflammatory environment (neutrophil count < 4.38 × 109 L (n = 83)). We also determined the levels of lymphocytes, monocytes, platelet count (PLT), mean platelet volume (MPV), platelet aggregation, the levels of cortisol and cholesterol and the concentrations of C reactive protein (CRP) and fibrinogen. Results: We found that CRP, fibrinogen and cortisol concentrations were statistically significantly higher in the group with higher neutrophil counts. However, there were no differences among cholesterol concentration and other markers of platelet function between the groups. We also showed that PLT, leukocyte and monocyte counts were higher in the group with a higher neutrophil count, and the PLT correlated with other cell type count and CRP. In addition, the neutrophil count correlated with concentrations of fibrinogen, evening cortisol and CRP. Conclusions: Cortisol, fibrinogen and CRP levels, PLT and monocyte counts were higher in the CHFrEF patient group with higher neutrophil counts. The cholesterol levels and platelet function readings did not differ between the groups. The neutrophil count correlated with evening cortisol concentration.


Assuntos
Insuficiência Cardíaca , Neutrófilos , Biomarcadores , Colesterol , Humanos , Hidrocortisona , Contagem de Leucócitos , Volume Plaquetário Médio , Volume Sistólico
13.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(3): 350-356, 2021 Jun 30.
Artigo em Chinês | MEDLINE | ID: mdl-34238410

RESUMO

Objective To compare the performance of contrast-enhanced ultrasound(CEUS)and ultrasound(US)in the differential diagnosis between cholesterol polyps and gallbladder adenomas. Methods A total of 136 patients with gallbladder polyp lesions(GPLs)and undergoing cholecystectomy in the First Medical Center of Chinese PLA General Hospital from January 2019 to October 2020 were retrospectively analyzed.All the patients underwent US and CEUS examinations before cholecystectomy.US and CEUS images of cholesterol polyps and gallbladder adenomas were compared for the evaluation of the performance of CEUS in the diagnosis of gallbladder adenomas. Results The 136 cases of GPLs included 95 cases of cholesterol polyps and 41 cases of gallbladder adenomas.Cholesterol polyps and gallbladder adenomas showed significant differences in the maximum size of GPLs( Z=-5.189, P<0.001), polyp blood flow signal(χ 2=33.630, P<0.001), vascular stalk width(Z=-7.366, P<0.001), polyp enhancement time(χ 2=22.487, P<0.001), enhancement intensity in arterial phase(χ 2=44.371, P<0.001), polyp vascular morphology(χ 2=53.814, P<0.001)and gallbladder wall integrity(χ 2=13.277, P=0.001).The sensitivity, specificity and accuracy of CEUS in distinguishing gallbladder adenomas from cholesterol polyps were 85.37%, 89.47% and 88.24%, respectively, and the area under the curve was 0.874. Conclusion CEUS can effectively distinguish gallbladder adenomas from cholesterol polyps and help patients with GPLs to select the appropriate treatment.


Assuntos
Adenoma , Vesícula Biliar , Adenoma/diagnóstico por imagem , Colesterol , Meios de Contraste , Diagnóstico Diferencial , Vesícula Biliar/diagnóstico por imagem , Humanos , Estudos Retrospectivos , Ultrassonografia
14.
Int J Mol Sci ; 22(11)2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34204880

RESUMO

Dysregulated mammalian target of rapamycin (mTOR) activity is associated with various neurodevelopmental disorders ranging from idiopathic autism spectrum disorders (ASD) to syndromes caused by single gene defects. This suggests that maintaining mTOR activity levels in a physiological range is essential for brain development and functioning. Upon activation, mTOR regulates a variety of cellular processes such as cell growth, autophagy, and metabolism. On a molecular level, however, the consequences of mTOR activation in the brain are not well understood. Low levels of cholesterol are associated with a wide variety of neurodevelopmental disorders. We here describe numerous genes of the sterol/cholesterol biosynthesis pathway to be transcriptionally regulated by mTOR complex 1 (mTORC1) signaling in vitro in primary neurons and in vivo in the developing cerebral cortex of the mouse. We find that these genes are shared targets of the transcription factors SREBP, SP1, and NF-Y. Prenatal as well as postnatal mTORC1 inhibition downregulated expression of these genes which directly translated into reduced cholesterol levels, pointing towards a substantial metabolic function of the mTORC1 signaling cascade. Altogether, our results indicate that mTORC1 is an essential transcriptional regulator of the expression of sterol/cholesterol biosynthesis genes in the developing brain. Altered expression of these genes may be an important factor contributing to the pathogenesis of neurodevelopmental disorders associated with dysregulated mTOR signaling.


Assuntos
Colesterol/genética , Neurônios/metabolismo , Proteínas Quinases/genética , Proteínas de Ligação a Elemento Regulador de Esterol/genética , Serina-Treonina Quinases TOR/genética , Animais , Autofagia/genética , Fator de Ligação a CCAAT/genética , Córtex Cerebral/crescimento & desenvolvimento , Córtex Cerebral/metabolismo , Colesterol/biossíntese , Regulação da Expressão Gênica no Desenvolvimento/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Camundongos , Neurogênese/genética , Cultura Primária de Células , Transdução de Sinais/genética , Transcrição Genética/genética
15.
Vestn Otorinolaringol ; 86(3): 127-133, 2021.
Artigo em Russo | MEDLINE | ID: mdl-34269036

RESUMO

The report presents modern views on the origin and pathomorphological characteristics of the cholesterol granuloma of the petrous apex of temporal bone, its clinical comparison with congenital cholesteatoma of the same localization. The differential diagnostic features in CT and MRI scans are analyzed in detail, and the principles of surgical treatment, indications and contraindications are discussed. Also the case of atypical course of cholesterol granuloma is presented, which was difficult in the diagnostics but with a successful treatment result.


Assuntos
Colesteatoma , Tomografia Computadorizada por Raios X , Colesteatoma/diagnóstico , Colesteatoma/cirurgia , Colesterol , Granuloma , Humanos , Imageamento por Ressonância Magnética , Osso Petroso/cirurgia , Osso Temporal/diagnóstico por imagem , Osso Temporal/cirurgia
16.
Trop Anim Health Prod ; 53(3): 380, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34191160

RESUMO

This research was done to detect some meat quality traits and tissue fatty acid combination of the longissimus dorsi thoracis (LT) muscle of Brown Swiss bulls at the different slaughter weights (SW). The animal material of the study comprised 20 Brown Swiss bulls. In the study, Brown Swiss bulls were divided into two groups according to their SW as low (LSW (n = 10); 431-503 kg) and high (HSW (n = 10); 504-583 kg). In the study, the LSW group showed the lowest final pH value (pHF) (5.44) (P < 0.05). As the SW increase, the L* (lightness) value decreased in the LT muscle of Brown Swiss bulls (P > 0.05). In the research, the differences observed between the SW groups considering a* (redness) and C (chroma) values were found significant (P < 0.05). LT muscle water holding capacity (PL) decreased (P < 0.01) with increasing slaughter weight. In the study, the differences observed between SW groups in terms of drip losses (DL) after 3-day (DRP3) and 7-day (DRP7) storages and cooking losses (CL) determined were found insignificant (P > 0.05). Freeze-thaw loss (FL) and ether extract (PEE) were found 4.35% and 1.01% higher, respectively, in the HSW group than the LSW group (P < 0.05). Cholesterol content was determined as 66.15 and 70.68 mg 100 g-1 meat in LSW and HSW groups, respectively. The ratios of n-6/n-3 (P < 0.05) and PUFA/SFA (P > 0.05) in the LT muscle decreased with the increase of SW. As a result, when LSW and HSW slaughter weight groups were evaluated considering the water losses causing financial losses in meat and fatty acids having beneficial effects on human health, it was seen that the LSW group came to the fore.


Assuntos
Ácidos Graxos , Carne , Animais , Peso Corporal , Bovinos , Colesterol , Culinária , Ácidos Graxos/análise , Masculino , Carne/análise
17.
J Proteome Res ; 20(7): 3463-3474, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34080435

RESUMO

The COVID-19 pandemic has become a worldwide health crisis. So far, most studies have focused on the epidemiology and pathogenesis of this infectious disease. Little attention has been given to the disease sequelae in patients recovering from COVID-19, and nothing is known about the mechanisms underlying these sequelae. Herein, we profiled the serum proteome of a cohort of COVID-19 patients in the disease onset and recovery stages. Based on the close integration of our proteomic analysis with clinical data, we propose that COVID-19 is associated with prolonged disorders in cholesterol metabolism and myocardium, even in the recovery stage. We identify potential biomarkers for these disorders. Moreover, severely affected patients presented more serious disturbances in these pathways. Our findings potentially support clinical decision-making to improve the prognosis and treatment of patients.


Assuntos
COVID-19 , Proteômica , Colesterol , Humanos , Miocárdio , Pandemias , Proteoma , SARS-CoV-2
18.
Molecules ; 26(9)2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-34066903

RESUMO

The effect of effective microorganisms (EM) on internal organ morphology, intestinal morphometry, and serum biochemical activity in Japanese quails under Clostridium perfringens challenge was determined. After 30 days of EM addition, one group of quails was orally inoculated with Clostridium perfringens. The second group did not receive EM and was inoculated with C. perfringens. In the gut, EM supplementation reduced the number of lesions, enhanced gut health, and protected the mucosa from pathogenic bacteria. EM showed an anti-inflammatory effect and fewer necrotic lesions in villi. In the internal organs, EM showed a protective effect against a typical lesion of C. perfringens infection. Necrosis and degeneration of the hepatocytes, necrosis of bile ducts, and bile duct proliferation were more severe in the infected group without EM. Morphometric evaluation showed significantly higher villi in the jejunum after EM addition. A greater crypt depth was observed in the C. perfringens group. Biochemical analysis of the blood indicated lower cholesterol on the 12th day of the experiment and between-group differences in total protein, lactate dehydrogenase (LDH), and albumin levels in the EM group. Further studies are needed to improve EM activity against pathologic bacteria as a potential alternative to antibiotics and to develop future natural production systems.


Assuntos
Anti-Inflamatórios/uso terapêutico , Doenças das Aves/sangue , Doenças das Aves/dietoterapia , Infecções por Clostridium/sangue , Infecções por Clostridium/dietoterapia , Clostridium perfringens , Enterite/sangue , Enterite/dietoterapia , Mucosa Intestinal/microbiologia , Probióticos/uso terapêutico , Substâncias Protetoras/uso terapêutico , Codorniz/sangue , Codorniz/microbiologia , Ração Animal/microbiologia , Animais , Ductos Biliares/patologia , Doenças das Aves/microbiologia , Colesterol/sangue , Infecções por Clostridium/microbiologia , Enterite/microbiologia , Feminino , Hepatócitos/patologia , Mucosa Intestinal/patologia , Jejuno/microbiologia , Jejuno/patologia , L-Lactato Desidrogenase/sangue , Necrose , Albumina Sérica/análise , Resultado do Tratamento
19.
Molecules ; 26(9)2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066579

RESUMO

Mass spectrometry imaging is a powerful tool for analyzing the different kinds of molecules in tissue sections, but some substances cannot be measured easily, due to their physicochemical properties. In such cases, chemical derivatization could be applied to introduce the charge into the molecule and facilitate its detection. Here, we study cholesterol derivatization with betaine aldehyde from tissue slices and evaluate how different sample preparation methods influence the signal from the derivatization product. In this study, we have tested different solutions for betaine aldehyde, different approaches to betaine aldehyde deposition (number of layers, deposition nozzle height), and different MALDI matrices for its analysis. As a result, we proved that the proposed approach could be used for the analysis of cholesterol in different tissues.


Assuntos
Betaína/análogos & derivados , Colesterol/análise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Animais , Betaína/química , Encéfalo/metabolismo , Cerebelo/metabolismo , Colesterol/química , Íons , Rim/metabolismo , Limite de Detecção , Fígado/metabolismo , Camundongos
20.
Molecules ; 26(11)2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34067439

RESUMO

Ezetimibe is a well-known drug that lowers blood cholesterol levels by reducing its absorption in the small intestine when joining to Niemann-Pick C1-like protein (NPC1L1). A ligand-based study on ezetimibe analogues is reported, together with one-hit synthesis, highlighted in the study. A convenient asymmetric synthesis of (2S,3S)-N-α-(R)-methylbenzyl-3-methoxycarbonylethyl-4-methoxyphenyl ß-lactam is described starting from Baylis-Hillman adducts. The route involves a domino process: allylic acetate rearrangement, stereoselective Ireland-Claisen rearrangement and asymmetric Michael addition, which provides a δ-amino acid derivative with full stereochemical control. A subsequent inversion of ester and acid functionality paves the way to the lactam core after monodebenzylation and lactam formation. It also shows interesting results when it comes to a pharmacophore study based on ezetimibe as the main ligand in lowering blood cholesterol levels, revealing which substituents on the azetidine-2-one ring are more similar to the ezetimibe skeleton and will more likely bind to NPC1L1 than ezetimibe.


Assuntos
Técnicas de Química Sintética , Desenho de Fármacos , Ezetimiba/análogos & derivados , Ezetimiba/síntese química , Alelos , Amidas/química , Aminoácidos/química , Anticolesterolemiantes/administração & dosagem , Anticolesterolemiantes/síntese química , Colesterol/sangue , Humanos , Ligantes , Espectroscopia de Ressonância Magnética , Proteínas de Membrana Transportadoras/metabolismo , Simulação de Acoplamento Molecular , Piridinas/química , Estereoisomerismo
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