Investigation of associations between apolipoprotein A5 and C3 gene polymorphisms with plasma triglyceride and lipid levels

SUMMARY OBJECTIVE: The aim of this study was to determine frequency and associations between APOA5 c.56C>G, −1131T>C, c.553G>T, and APOC3 −482C>T and SstI gene polymorphisms with hypertriglyceridemia. METHODS: Under a case-control study model, 135 hypertriglyceridemic and 178 normotriglyceridemic control participants were recruited. Polymerase chain reaction and restriction fragment length polymorphism methods were utilized for genotyping. Statistical calculations were performed by comparing allele and genotype frequencies between groups. Clinical characteristics were compared between groups and intra-group genotypes. RESULTS: APOC3 gene −482C>T and SstI polymorphic genotypes and allele frequencies were significantly higher in hypertriglyceridemic group (genotype frequencies, p=0.035, p=0.028, respectively). Regression analysis under unadjusted model confirmed that APOC3 −482C>T and SstI polymorphisms were significantly contributing to have hypertriglyceridemia (p=0.02, odds ratio [OR]=1.831 (95% confidence interval [CI] 1.095-3.060); p=0.04, OR=1.812 (1.031-3.183), respectively). APOA5 c.56C>G was in complete linkage disequilibrium with APOA5 c.553G>T polymorphism (D'=1). CONCLUSION: For the first time in a population sample from Turkey, among the five polymorphisms of APOA5 and APOC3 genes investigated, APOC3 −482C>T and SstI polymorphisms were associated with elevated serum TG levels, while APOA5 c.56C>G, −1131T>C, and c.553G>T polymorphisms were not.

Serum amyloid A in children and adolescents: association with overweight and carotid intima-media thickness

ABSTRACT Objective To compare serum amyloid A concentrations between overweight and eutrophic children and adolescents and to relate it to lipid profiles, glucose tolerance, and carotid intima-media thickness. Methods One hundred children and adolescents (mean age: 10.8±3.16 years) were included and divided into two groups: overweight and non-overweight. The following were evaluated: Z-score body mass index, carotid intima-media thickness, lipid metabolism biomarkers (lipid profile and apolipoproteins A1 and B), inflammatory biomarkers (ultra-sensitive C-reactive protein and serum amyloid A), and glucose homeostasis model assessment of insulin resistance. Results The groups were homogeneous in age, sex, and pubertal stage. Higher levels of triglycerides, apolipoprotein B, homeostasis model assessment of insulin resistance, ultrasensitive C-reactive protein, serum amyloid A, and carotid intima-media thickness were observed in the overweight group. In the multivariate analysis, age (OR=1.73; 95%CI: 1.16-2.60, p=0.007), Z-score body mass index (OR=3.76; 95%CI: 1.64-8.59, p=0.002), apolipoprotein-B (OR=1.1; 95%CI: 1.01-1.2, p=0.030), and carotid intima-media thickness (OR=5.00; 95%CI: 1.38-18.04, p=0.014) were independently associated with serum amyloid A levels above the fourth quartile of the studied sample (>9.4mg/dL). Conclusion Overweight children and adolescents had higher serum amyloid A concentrations than eutrophic children. There was an independent association between higher concentrations of serum amyloid A and Z-score, body mass index, apolipoprotein B, and carotid intima-media thickness, indicating the importance of this inflammatory biomarker in identifying the early risk of atherosclerosis.

Associações entre Obesidade Eutrófica e Alterações no Perfil Lipídico de Adultos Jovens / Associations between Normal-Weight Obesity and Disturbances in the Lipid Profile of Young Adults

Resumo Fundamento A obesidade eutrófica (OE) é caracterizada por índice de massa corporal (IMC) normal, mas com alto percentual de gordura corporal (%GC), o que aumenta os riscos de comorbidades cardiometabólicas. A avaliação e interpretação precisas dos dados de composição corporal são necessárias para reduzir esses riscos. Objetivos Comparar o perfil cardiometabólico de indivíduos com OE e %GC normal e avaliar os fatores de risco associados. Métodos Foi realizado estudo transversal com 222 adultos brasileiros de uma comunidade universitária, dos quais 157 tinham OE e 65 tinham IMC e %GC normais (grupo sem OE). Todos os participantes relataram ser assintomáticos e sem problemas de saúde subjacentes. Foram avaliadas características socioeconômicas, estilo de vida, consumo alimentar, antropometria, medidas de composição corporal (por meio de absorciometria radiológica de dupla energia) e perfis lipídico e glicêmico. Valor de p < 0,05 foi estabelecido como significativo. Resultados A mediana de idade dos participantes foi de 23 anos (intervalo interquartil: 21 a 25), sendo a maioria do sexo feminino (67,1%). Não foram encontradas diferenças significativas na pressão arterial, idade ou nível de atividade física entre os grupos com e sem OE. No entanto, a frequência de distúrbios do perfil lipídico foi maior no grupo com OE (54%) em comparação com o grupo sem OE (34%) (p < 0,006). Circunferência do pescoço, %GC e distúrbios do perfil lipídico foram positivamente associados com a OE. Conclusão Indivíduos com OE apresentam pior perfil cardiometabólico do que aqueles sem OE, e essa condição está associada a importantes biomarcadores. Torna-se importante abordar esses resultados para prevenir complicações cardiometabólicas de longo prazo. A avaliação e a interpretação precisas dos dados da composição corporal, independentemente do IMC, são cruciais nesse cenário.

Abstract Background Normal-weight obesity (NWO) is characterized by normal body mass index (BMI) but high body fat percentage (%BF) that increases the risks of cardiometabolic comorbidities. Accurate assessment and interpretation of body composition data are necessary to reduce these risks. Objectives To compare the cardiometabolic profile of individuals with NWO and normal %BF and evaluate the associated risk factors. Methods A cross-sectional study was conducted with 222 Brazilian adults from a university community, of whom 157 had NWO and 65 had normal BMI and %BF (non-NWO). All participants reported being asymptomatic and without underlying health conditions. Socioeconomic, lifestyle, food intake, anthropometry, body composition measures (using dual-energy radiological absorptiometry), and lipid and glycemic profiles were evaluated. A p < 0.05 was established as significant. Results The median age of the participants was 23 years (interquartile range: 21 to 25), and most were female (67.1%). No significant differences were found in blood pressure, age, or physical activity levels between the NWO and non-NWO groups. However, the frequency of lipid profile disturbances was higher in the NWO group (54%) compared to the non-NWO group (34%) (p < 0.006). Neck circumference, %BF, and lipid profile disturbances were positively associated with NWO. Conclusion Individuals with NWO have a worse cardiometabolic profile than those without NWO, and this condition is associated with important biomarkers. Addressing these outcomes is important for preventing long-term cardiometabolic complications. Accurate assessment and interpretation of body composition data, regardless of BMI, are crucial in this scenario.

Association of serum lipoproteins and inflammatory parameters derived from the blood test with renal function in COVID-19 outpatients

Abstract Changes in lipoprotein metabolism are among the main causes of hemodynamic impairment in renal function. COVID-19 is an multisystemic inflammatory disease, aggravating this situation. This cross-sectional study investigated the relationship of serum lipoprotein profile with inflammatory parameters and renal function in 95 COVID-19 outpatients in comparison with 173 with flu-like symptoms. Serum samples were collected for the determination of total cholesterol and fractions, apolipoproteins (Apo A-I and Apo B), urea (sUr) and creatinine (sCr). The glomerular filtration rate (eGFR) was calculated. Neutrophil/lymphocyte (NLR) and platelet/lymphocyte (PLR) ratios were calculated as inflammatory parameters derived from the blood tests. COVID-19 patients presented lower high-density lipoprotein cholesterol (HDL-c) (47.90 ± 1.543 vs. 51.40 ± 0.992) and higher PLR (190.9 ± 9.410 vs. 137.6 ± 5.534) and NLR (3.40 ± 0.22 vs. 2.80 ± 0.15). Both NLR and PLR correlated with each other (r = 0.639). Furthermore, the Apo B/Apo A-I ratio was correlated with PLR (r = 0.5818) and eGFR (r = -0.2630). COVID-19 patients classified as at high risk of developing acute myocardial infarction based on the Apo B/ Apo A-I ratio had higher values for sUr/sCr. Thus, serum apolipoproteins, PLR, and NLR could be related to renal dysfunction in COVID-19.

Lipoprotein glomerulopathy caused by mutation of apolipoprotein E gene in children: a report of two cases / 中华肾脏病杂志

The paper reports two cases of lipoprotein glomerulopathy (LPG) in children. The Sanger sequencing results in 2 cases indicated apolipoprotein E gene mutation[c.127 (exon3) C>T, p.R43C (p.Arg43Cys); c.494 (exon4) G>C, p.R165P (p.Arg165Pro),respectively]. Renal pathological presentation of two children showed that a large number of lipoprotein emboli were formed in the glomerular capillary loop, and the diagnosis of LPG was confirmed. The onset of LPG has no specific clinical manifestation, which is easy to be undiagnosed or misdiagnosed. Renal biopsy is a diagnostic means, glucocorticoid treatment is ineffective, and long-term lipid-lowering treatment may be required for LPG.

Interaction between apolipoprotein E genotypes, excessive daytime sleepiness, and cognitive function in obstructive sleep apnea patients / Interação entre genótipos da apolipoproteína E, sonolência excessiva diurna e função cognitiva em pacientes com apneia obstrutiva do sono

Abstract Background Some studies show an association between the apolipoprotein E ε4 allele (ApoEε4) and obstructive sleep apnea syndrome (OSAS), and other studies, an association between ApoEε4 and excessive daytime sleepiness (EDS), but there are no data in the literature on the interaction between EDS, cognitive function, and ApoEε4 in patients with OSA. Objective To examine the cognitive function of adults with and without EDS and with and without ApoEε4. Methods A total of 21 male and female patients aged between 33 and 79 years, underwent a clinical interview, ApoE genotyping, neuropsychological evaluation, polysomnography, and the application of the Epworth Sleepiness Scale. Results Excessive daytime sleepiness was associated with lower intelligence quotient (IQ; total performance) and worse immediate visual memory, regardless of the ApoE genotype. Patients carrying the ApoEε3/ε4 genotype had a worse performance in divided attention, constructional praxis, perceptual organization, and cognitive flexibility. A combination of the ε4 allele and EDS potentiates the negative effect on cognition, except for immediate visual memory. In this case, patients had a worse performance in terms of processing speed, selective attention, and visuomotor coordination. Conclusions Excessive daytime sleepiness and the ApoEε3/ε4 genotype are associated with worse cognitive performance in OSA patients. The combination of EDS and ε4 allele potentiates cognitive impairment.

Resumo Antecedentes Alguns estudos mostram uma associação entre o alelo ε4 da apolipoproteina E (ApoEε4) e a síndrome da apneia obstrutiva do sono (SAOS), e outros, entre ApoEε4 e a sonolência excessiva diurna (SED), mas não há dados na literatura sobre a interação entre SED, função cognitiva e ApoEε4 em pacientes com SAOS. Objetivo Avaliar a função cognitiva em adultos com SAOS com e sem SED e com e sem ApoEε4. Métodos Ao todo, 21 pacientes, de 33 a 79 anos, homens e mulheres, foram avaliados clinicamente, e submetidos a genotipagem ApoE, avaliação neuropsicológica, polissonografia, e aplicação da Escala de Sonolência de Epworth. Resultados A SED esteve associada com menor quociente de inteligência (QI; desempenho geral) e pior memória visual imediata, independentemente do genótipo ApoE. Pacientes com genótipo ApoEε3/ε4 apresentaram pior desempenho na atenção dividida, praxe construcional, organização perceptiva e flexibilidade cognitiva. A combinação do alelo ε4 com a SED potencializa esse efeito deletério na cognição, exceto na memória visual imediata. Nesse caso, os pacientes tiveram uma menor velocidade de processamento cognitivo, e piores atenção seletiva e coordenação visiomotora. Conclusões A SED e o genótipo ApoEε3/ε4 estão associados a um pior desempenho cognitivo em pacientes com SAOS. A combinação de SED e do alelo ε4 potencializa esse efeito.

Effect of Gravidity on Cardiovascular Markers in Normotensive Pregnant Women

Gravidity, or the number of pregnancies a woman has had, is linked to a number of biochemical alterations, including changes in cardiovascular parameters. These modifications may increase the likelihood of cardiovascular disease in this population. The aim of this research was to evaluate the effect gravidity has on some cardiovascular markers among normotensive pregnant women. A cross-sectional study of 100 women of reproductive age was carried out at Rivers State University and Rivers State University Teaching Hospital, the subjects were chosen at random for the study. Blood samples were taken and tested for total cholesterol, triglycerides, high density lipoprotein, uric acid, and Apolipoprotein A1 and B. Apolipoprotein A1 and B were all measured in blood samples for biochemical analysis. The levels of low density lipoprotein and very low density lipoprotein were determined. Graph Pad Prism Version 8.0.2.263 was used to analyze the data from the study. Result gotten from the study showed that Gravidity had no significant effect on biochemical parameters (TC, TG, UA, LDL, Apo A1, Apo B, CRP, and VLDL) in pregnant women (P>0.05), but there was a significant increase (P<0.05) in HDL levels among the group; 0.87 ± 0.21 (1-2), 0.93 ± 0.21 (3-4), 0.86 ± 0.12(5-6) and 1.30 ± 0.00 for (7-8). The effect of gravidity (1-2, 3-4, 5-6, 7-8) on HDL was shown to be significant for ANOVA and Turkey post hoc multiple comparison test; (1-2 vs 7-8) (P= 0.0204) and (5-6 vs 7-8) (P= 0.0250).. This study demonstrated that gravidity had little or no effect on the biochemical parameters but increases the HDL cholesterol level in normotensive pregnant women.

Apolipoprotein B and ischemic stroke / 国际脑血管病杂志

Studies have shown that plasma apolipoprotein B (ApoB) has a good predictive value for ischemic stroke and plays an important role in the prevention and treatment of ischemic stroke. More and more guidelines and consensus opinions began to recommend ApoB as a routine intervention target. This article reviews the biological characteristics, clinical detection advantages, and role and treatment prospect of ApoB in the prevention and treatment of ischemic stroke.

Analysis of solute carrier organic anion transporter family member 1b1 and apolipoprotein E genes in a population from southern Yunnan / 中国基层医药

Objective:To analyze the distribution of solute carrier organic anion transporter family member 1b1 ( SLCO1B1) and apolipoprotein E ( ApoE) genes in a population from southern Yunnan. Methods:The data of 104 patients who received treatment in Southern Central Hospital of Yunnan Province (The First People's Hospital of Honghe State) between May 2019 and June 2020 were collected. The distribution of SLCO1B1 and ApoE genes and their relationship with nationality, sex, and age were analyzed and compared between different regions. Results:The percentage of patients carrying *1a/*1a, *1a/*1b, *1b/*1b, *1a/*15, *1b/*15, five phenotypes of SLCO1B1 gene, in the population from southern Yunnan was 4.81%, 32.69%, 42.31%, 12.50% and 7.69% respectively. Phenotypes *1a/*5, *5/*5, *5/*15 and *15/*15 were not detected. Normal metabolic phenotype of SLCO1B1 accounted for 79.81%, and intermediate metabolic phenotype of SLCO1B1 accounted for 20.19%. Weak metabolic phenotype was not detected. The percentage of patients carrying E2/E2, E2/E3, E3/E3, E3/E4, E4/E4, five phenotypes of ApoE gene in the population from southern Yunnan was 0.96%, 16.35%, 70.19%, 11.54% and 0.96% respectively. E2/E4 phenotype was not detected. The percentage of patients with ApoE protective phenotype, ApoE normal phenotype, and ApoE risk phenotype was 17.31%, 70.19% and 12.50% respectively. The observed polymorphism mutation frequency of SLCO1B1 and ApoE genes was consistent with the Hardy-Weinberg equilibrium ( P > 0.05), suggesting constancy and a population representation. The Fisher test showed that SLCO1B1 gene distribution differed significantly between ethnic minorities and Han nationality in southern Yunnan ( P = 0.013). There was no significant difference in SLCO1B1 gene distribution between different sexes and between different ages (all P > 0.05). There was no significant difference in ApoE gene distribution between ethnic minorities and Han nationality, between different sexes, and between different ages in the population from southern Yunnan (all P > 0.05). Conclusion:SLCO1B1 gene distribution is related to nationality in the population from southern Yunnan, but it is unrelated to sex and age. ApoE gene distribution is unrelated to nationality, sex and age.

Analysis of small dense low-density lipoprotein cholesterol level and the relationship with corresponding lipid components in healthy adults / 中华检验医学杂志

Objective:To investigate the small and dense low density lipoprotein cholesterol (sdLDL-C) level, ratios of sdLDL-C/low density lipoprotein cholesterol (LDL-C), sdLDL-C/high density lipoprotein cholesterol (HDL-C) and sdLDL-C/apolipoprotein B (apoB), and their correlation with lipid components in healthy adults.Methods:A total of 1 151 healthy adults, who underwent physical examination in Beijing Anzhen Hospital Affiliated to Capital Medical University from September to December 2020 (557 men and 594 women), were included in this study. They were divided into five age groups: 18-29 years old ( n=247), 30-44 years old ( n=269), 45-59 years old ( n=225), 60-74 years old ( n=207) and 75-90 years old ( n=203) according to the age classification standard of the United Nations World Health Organization in 2018. The levels of total cholesterol (TC), triglyceride (TG), HDL-C, LDL-C, sdLDL-C, apoA1 and apoB were measured, and the distribution of sdLDL-C, sdLDL-C/LDL-C, sdLDL-C/HDL-C and sdLDL-C/apoB in different sex and age groups were analyzed. Pearson/Spearman correlation was used to analyze the correlation between the above four indexes and other blood lipid components. Results:SdLDL-C, sdLDL-C/LDL-C, sdLDL-C/HDL-C and sdLDL-C/apoB were higher in male group ([0.56±0.23] mmol/L, 0.24±0.07, 0.49±0.22, 0.27±0.07) than those in female group ([0.48±0.18] mmol/L, 0.20±0.06, 0.36±0.17, 0.23±0.07) (all P<0.01). SdLDL-C, sdLDL-C/LDL-C, sdLDL-C/HDL-C and sdLDL-C/apoB were different among different age groups of male and female participants (all P<0.001). SdLDL-C level was significantly higher in males than in females among 18-29 years old group, 30-44 years old group, 45-59 years old group (all P<0.05). SdLDL-C, sdLDL-C/LDL-C, sdLDL-C/HDL-C and sdLDL-C/apoB were higher in males of 18-29 years old group, 30-44 years old group, 45-59 years old group and 60-74 years old group than in females of corresponding age groups (all P<0.05). The level of sdLDL-C of all participants was positively correlated with TC, TG, LDL-C, apoB, non-HDL-C and remnant cholesterol ( r＝0.50, 0.45, 0.67, 0.68, 0.61, 0.11, all P<0.01), and negatively correlated with HDL-C and apoA1 ( r＝-0.17 and -0.10, P<0.01). Conclusions:The levels of sdLDL-C, sdLDL-C/LDL-C, sdLDL-C/HDL-C and sdLDL-C/apoB in healthy adults are different in healthy adults of different ages and sex. There is a high correlation between sdLDL-C and apoB.

Vascular mild cognitive impairment and its relationship to hemoglobin A1c levels and apolipoprotein E genotypes in the Dominican Republic / Comprometimento cognitivo leve vascular e sua relação com os níveis de hemoglobina a1c e genótipos apolipoproteína e na república dominicana

ABSTRACT. Dementia and vascular mild cognitive impairment (VaMCI) currently impose a tremendous human and economic burden on patients from aging populations and their families worldwide. Understanding the interplay of cardiometabolic risk factors and apolipoprotein E (APOE) may direct us to a more personalized medicine and preventative care in MCI and dementia. Objective: To evaluate the relationship of cardiometabolic risk factors with MCI and assess the APOE genotype's role in an elderly cohort in the Dominican Republic. Methods: We studied a cohort of 180 participants 65 years of age and older using a combined assessment of cardiometabolic risk factors, neuropsychological battery tests, and APOE genotyping. We used the number of failed tests as a proxy to predict MCI. Results: We found that patients with the ε3-ε4 APOE genotype had 2.91 higher number of failed cognitive tests (p=0.027) compared to patients with the ε3-ε3 genotyped. The rate of test failures increased 10% (p=0.025) per unit increase in HbA1c percentage. Conclusions: Increased Hemoglobin A1c levels and ε3-ε4 APOE genotypes seem to have an association with the development of VaMCI.

RESUMO. A demência e o comprometimento cognitivo leve vascular (VaMCI) atualmente impõem uma enorme carga humana e econômica aos pacientes de populações envelhecidas e suas famílias em todo o mundo. Compreender a interação dos fatores de risco cardiometabólicos e apolipoproteína E (APOE) pode nos direcionar para uma medicina mais personalizada e de cuidados preventivos em MCI e demência. Objetivo: Avaliar a relação dos fatores de risco cardiometabólicos com o MCI e o papel do genótipo APOE em uma coorte de idosos na República Dominicana. Métodos: Estudamos uma coorte de 180 participantes com 65 anos de idade ou mais, utilizando uma avaliação combinada de fatores de risco cardiometabólicos, uma bateria de testes neuropsicológicos e genotipagem APOE. Adotou-se o número de testes com mau desempenho para o diagnóstico de MCI. Resultados: Verificou-se que os pacientes com o genótipo ε3-ε4 do APOE apresentaram 2,91 vezes mais testes cognitivos com mau desempenho (p=0,027) em comparação com os pacientes com o genótipo ε3-ε3. A taxa de falhas de teste aumentou 10% (p=0,025) por aumento de unidade na porcentagem de HbA1c. Conclusões: Níveis mais altos de HbA1c e os genótipos ε3-ε4 do APOE parecem estar associados ao desenvolvimento de VaMCI.

Interaction between physical exercise and APOE gene polymorphism on cognitive function in older people

We aimed to present an overview of the literature regarding the interaction between physical exercise and APOE gene polymorphism on cognitive function, particularly in patients with Alzheimer's disease (AD). Firstly, this review focused on the effect of the physical exercise on cognitive function, regardless of APOE gene polymorphism. Some studies have shown that a high level of cardiorespiratory fitness is associated with less neuronal damage with an improvement in memory score tests whereas other studies failed to detect any association between physical exercise and cognitive improvement either in healthy individuals or patients with AD. Taken together, standardized protocols and more longitudinal studies are required to provide a better insight into the effects of physical exercise on cognitive function. Although there is no agreement in the literature regarding the effects of physical exercise on cognitive function, it is well established that it improves social interaction and the feeling of well-being, thereby positively contributing to the quality of life of the elderly. Regarding the influence of physical exercise on cognitive function in APOE ε4 allele carriers, the data trend shows that the carriers of allele ε4 for APOE gene were more responsive to the beneficial effects of physical exercise on cognitive function compared with non-carriers. Nevertheless, studies with larger sample sizes will provide more accuracy about this relationship.

Association between apolipoprotein E polymorphism and myocardial infarction in patients with type 2 diabetes mellitus / 中华检验医学杂志

Objective:To investigate the relationship between the E2 and E4 alleles of apolipoprotein E (apoE) gene and myocardial infarction (MI) in type 2 diabetes Mellitus (T2DM) patients, and to explore the relationship between apoE polymorphism and blood lipid metabolism.Methods:This case control study was conducted from August 2016 to March 2020 in China-Japan Friendship Hospital, 3 459 inpatients with T2DM were included including 3 044 patients without MI (T2DM group) and 415 patients with MI (T2DM+MI group). Real time fluorescent quantitative PCR was used to detect apoE polymorphism. Automatic biochemical analyzer was used to detect lipid levels. Logistic regression analyses were performed to determine the association of apoE with risk of MI in patients with T2DM.Results:(1) The frequency of E4 allele in T2DM+MI group (12.29%, 102/830) was significantly higher than in T2DM group (9.13%,556/6 088), while the frequency of E2 allele in T2DM+MI group (7.35%,61/830) was significantly lower than that in T2DM group (8.21%,500/6 088), P=0.012. Logistic regression analyses showed that E4 allele carrier (E3/E4+E4/E4) faced a higher risk for MI in T2DM patients ( OR=1.48, 95% CI 1.14-1.92, P=0.003), while E2 allele carrier(E2/E3+E2/E2)did not face a higher risk of MI in T2DM patients ( OR=0.88, P=0.642). (2) The levels of apoE polymorphism and blood lipid: The levels of TC, LDL-C and apoB increased in the order of E4 allele, wild type and E2 allele ( P<0.05). The levels of HDL-C, apoA1 and apoE decreased in the order of E4 allele, Wild type and E2 allele ( P<0.05). Conclusion:The E4 allele is a risk factor for MI in T2DM patients, and apoE polymorphism can affect blood lipid level in this patent cohort.

Role of Erbin in sepsis-associated encephalopathy in mice and the relationship with NLRP3 inflammasomes / 中华麻醉学杂志

Objective:To evaluate the role of ErbB2 interacting protein (Erbin) in sepsis-associated encephalopathy (SAE) in mice and the relationship with nod-like receptor thermoprotein domain associated protein 3 (NLRP3) inflammasomes.Methods:Sixty SPF-grade healthy male wild-type C57BL/6 mice and 60 Erbin (-/-)C57BL/6 mice, aged 8-10 weeks, weighing 20-25 g, were divided into 4 groups ( n=30 each) by a random number table method: wild-type sham operation group (WT+ Sham group), wild-type SAE group (WT+ SAE group), Erbin (-/-) sham operation group (EKO+ Sham group) and Erbin (-/-) plus SAE group (EKO+ SAE group). The model of SAE was established by cecal ligation and perforation in anesthetized mice.Open field test (total distance moved) was performed at 7 days after establishing the model, new object recognition test (recognition index) was performed at 8 days after establishing the model, and Morris water maze test (time of staying at target quadrant) was performed at 10 days after establishing the model.The mice were sacrificed, and hippocampal tissues were removed for microscopic examination of pathologic changes (by HE staining) and for determination of neuron count, expression of NLRP3, caspase-1 and apoptosis-associated speck-like protein containing a CARD (ASC) (by Western blot), the number of NLRP3 positive cells (by immunohistochemistry), and contents of interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and IL-18 (by enzyme-linked immunosorbent assay). The cell survival rate was calculated. Results:Compared with group WT+ Sham, the time of staying at target quadrant was significantly shortened, the recognition index and cell survival rate were decreased, the contents of IL-1β, IL-18 and TNF-α and the number of NLRP3 positive cells were increased, and the expression of NLRP3, caspase-1 and ASC was up-regulated in group WT+ SAE ( P<0.05). Compared with group EKO+ Sham, the time of staying at target quadrant was significantly shortened, the recognition index and cell survival rate were decreased, the contents of IL-1β, IL-18 and TNF-α and the number of NLRP3 positive cells were increased, and the expression of NLRP3, caspase-1 and ASC was up-regulated in group EKO+ SAE ( P<0.05). Compared with group WT+ SAE, the time of staying at target quadrant was significantly shortened, the recognition index and cell survival rate were decreased, the contents of IL-1β, IL-18 and TNF-α and the number of NLRP3 positive cells were increased, and the expression of NLRP3, caspase-1 and ASC was up-regulated in group EKO+ SAE ( P<0.05). There was no significant difference in total distance moved between the four groups ( P>0.05). Conclusion:Erbin can exert endogenous protection by inhibiting the activation of NLRP3 inflammasomes in mice with SAE.

Mechanism of neuronal damage induced by sevoflurane: the relationship between phosphorylation of Tau protein and apolipoprotein E containing 18 kDa fragments / 中华麻醉学杂志

Objective:To evaluate the relationship between phosphorylation of Tau protein and apolipoprotein E (ApoE) containing 18 kDa fragments and investigate the mechanism of neuronal damage induced by sevoflurane.Methods:Primary neurons (ApoE3 and ApoE2 genotypes, 24 dishes for each genotype) of fetal mice cultured until the 5th day were divided into 4 groups ( n=12 each) using a random number table method: ApoE3 control group (A3C group), ApoE3 sevoflurane group (A3S group), ApoE2 control group (A2C group) and ApoE2 sevoflurane group (A2S group). Neurons were treated with 21% oxygen + 5% carbon dioxide + 4.1% sevoflurane for 4 h in A3S and A2S groups, while the neurons were only treated with 21% oxygen + 5% carbon dioxide in A3C and A2C groups.The cell proteins were then extracted to detect the expression of full-length ApoE and ApoE, AT8 and PHF1 containing 18 kDa fragments (by Western blot), expression of ApoE mRNA (by real-time polymerase chain reaction), and concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in the supernatant (by enzyme-linked immunosorbent assay). Results:Compared with A2C group, the expression of ApoE mRNA and full-length ApoE in neurons was up-regulated ( P<0.05), and no significant change was found in the expression of AT8 and PHF1 and concentrations of TNF-α and IL-6 in the supernatant in A2S group ( P>0.05). Compared with A3C group, the expression of ApoE mRNA, full-length ApoE, and ApoE, AT8 and PHF1 containing 18 kDa fragments was up-regulated, and the concentrations of TNF-α and IL-6 in the supernatant were increased in A3S group ( P<0.05). Conclusion:Sevoflurane may promote phosphorylation of Tau proteins and increase inflammatory responses through up-regulating the expression of ApoE containing 18 kDa fragments, thus leading to neuronal damage.

Apolipoprotein E genotypes and vascular cognitive impairment / 国际脑血管病杂志

Vascular cognitive impairment is the only cognitive impairment disease that can be intervened at present. In recent years, the research on its genetic factors has attracted much attention. Among them, apolipoprotein E (ApoE) and its genotypes are closely associated with lipid metabolism, β-amyloid aggregation and deposition, the changes of brain structure and function, and are closely correlated with the pathogenesis of dementia. This article discusses some possible mechanisms of ApoE and its genotypes affecting cognitive function, in order to provide reference for the management of cognitive function in patients with vascular cognitive impairment.

Adiposidade Corporal e Apolipoproteínas em Crianças e Adolescentes: Metanálise de Estudos Prospectivos / Body Adiposity and Apolipoproteins in Children and Adolescents: A Meta-Analysis of Prospective Studies

Resumo Fundamento Excesso de adiposidade corporal e doenças cardiovasculares são problemas mundiais com crescente prevalência em crianças e adolescentes, sendo necessário investigar a relação destes, afim de construir estratégias de enfrentamento. Objetivo Investigar influência do excesso de adiposidade corporal sobre os níveis séricos de apolipoproteínas B e A1 (ApoB e ApoA1) em crianças e adolescentes. Métodos Busca sistemática nas bases de dados Medline/PubMed, Embase, Lilacs, Web of Science, Ovid e Science Direct de coortes consideradas elegíveis, avaliando-se qualidade metodológica e risco de viés; estudos combináveis, com boa qualidade e baixo risco de viés foram analisados com metanálise; a medida sumária utilizada foi a diferença de média ponderada e seu respectivo intervalo de confiança a 95%. Resultados 8 artigos preencheram os critérios de elegibilidade, incluindo indivíduos com média de idade variando de 9 a 15,7 anos. Para a metanálise, incluíram-se 4 artigos, com total de 7.974 crianças e adolescentes. Observou-se aumento médio de 4,94 mg/dL (IC 95%: 4,22 a 5,67 mg/dL) nos níveis de ApoB naqueles com excesso de adiposidade. Para a ApoA1, identificou-se redução média de -8,13 mg/dL (IC 95%: - 9,09 a -7,17 mg/dL) nos níveis séricos desse marcador em indivíduos com maior adiposidade corporal. Além disso, a influência do excesso de adiposidade corporal sobre os níveis de ApoA1 e ApoB foi maior entre adolescentes do que entre crianças. Conclusões O excesso de adiposidade corporal influenciou tanto na redução dos valores de ApoA1 quanto no aumento dos níveis de ApoB em crianças e adolescentes, e tais alterações foram mais relevantes entre adolescentes.(Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

Abstract Background Excess Weight and Cardiovascular Diseases are health problems with increasing prevalence among children and adolescents, hence the need to investigate the issues related to them to better deal with the problem. Objective To investigate the influence of excess adiposity on the levels of apolipoprotein B and A1 in children and adolescents. Methods A systematic search was conducted in the PubMed, Embase, Lilacs, Web of Science, Ovid and Science direct databases, searching for cohort eligible studies and evaluating their results, methodological quality and risk of bias; combinable studies with good quality and low risk of bias were evaluated by meta-analysis. The summary measure used was the weighted mean difference (WMD) with its respective 95% confidence interval. Results 8 articles attended the eligibility criteria including individuals with age mean varying from 9 to 15.7 years of age. The meta-analysis included 4 articles with a total of 7,974 children and adolescents. It was observed a mean increase of 4,94mg/dL (95%CI: 4,22 to 5,67) in the ApoB levels in individuals with excess of body adiposity. For the ApoA1, we identified a mean reduction of -8,13mg/dL (95%CI: -9,09 to -7,17 mg/dL) in its levels in children and adolescents with higher body adiposity. Beside this, the influence of excess adiposity on the ApoB and ApoA1 levels was higher between adolescents than children. Conclusions The excess of body adiposity influenced both the reduction of ApoA1 values and the increase of ApoB levels, being these changes more relevant among adolescents. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

Armonizacion del estudio de lipidos en el laboratorio clinico / Harmonization of the study of lipids in the clinical laboratory

Los profesionales que ejercen la bioquimica clinica son conscientes de la falta de resultados comparables entre laboratorios, independientemente de donde y cuando se realicen. Durante muchos anos el centro de la gestion de la calidad estuvo en la estandarizacion de los procedimientos de medida, la armonizacion va mas alla del metodo y los resultados analiticos e incluye todos los aspectos que hay que tener en cuenta durante el proceso total de la prueba. Los laboratorios de bioquimica clinica han logrado en las ultimas decadas importantes mejoras en la calidad de los procesos analiticos, pero es necesario un esfuerzo mayor dedicado a la vulnerabilidad de los procedimientos extra analiticos para asegurar la comparacion y la concordancia de los resultados obtenidos por diferentes laboratorios clinicos. Las iniciativas destinadas a mejorar la armonizacion de los resultados de laboratorio tienen una dimension etica y de gran importancia en el diagnostico de las dislipemias asociadas al desarrollo de aterosclerosis y la evaluacion del riesgo cardiovascular. Los estudios poblacionales aun muestran dificultades en la identificacion del mejor biomarcador que pueda evidenciar adecuadamente el riesgo cardiovascular en un individuo. La correlacion, discordancia y concordancia muestran que es necesario el diseno de un perfil de pruebas de laboratorio personalizado, con marcadores estandarizados y armonizados, que permita la prediccion del riesgo.

The health professionals who practice clinical biochemistry are aware of the lack of comparable results between laboratories, regardless of where and when they are performed. For many years, the objective of the quality management was the standardization of measurement procedures. The harmonization is beyond the methods and the analytical results, and it includes all the aspects to be taken into account during the whole process of the test. The clinical biochemistry laboratories have achieved important improvements in the quality of the analytical processes in the last decades, but greater effort is necessary for the vulnerability of the extra analytical procedures to ensure the comparison and the agreement of the results obtained by different clinical laboratories. The initiatives aimed to improve the harmonization of laboratory results have an ethical dimension and importance in the diagnosis of dyslipidemia associated with the development of atherosclerosis and the assessment of cardiovascular risk. The population studies still show difficulties in the identification of the best biomarker that can adequately show the cardiovascular risk in an individual. The correlation, discordance and concordance between biomarkers show that it is necessary to design a personalized laboratory test profile, and with standardized and harmonized markers that allow the prediction of risk.

Os profissionais que exercem a bioquímica clínica Clinical estão cientes da falta de resultados comparáveis entre laboratórios, independentemente de onde e quando forem realizados. Por muitos anos, o centro de gestão da qualidade esteve na padronização dos procedimentos de medição, a harmonização vai além do método analítico e dos resultados analíticos e inclui todos os aspectos a considerar durante o processo do teste. Laboratórios bioquímica clínica têm alcançado, nas últimas décadas grandes melhorias na qualidade dos processos analíticos, mas precisa de um esforço maior dedicado à vulnerabilidade dos procedimentos extra-analíticos, para garantir a comparação e concordancia dos resultados obtidos pelos diferentes laboratórios clínicos. Iniciativas para melhorar a harmonização dos resultados laboratoriais têm uma dimensão ética e de grande importȃncia no diagnóstico de dislipidemias associadas ao desenvolvimento de aterosclerose e à avaliação do risco cardiovascular. As pesquisas populacionais mostram ainda dificuldades em identificar o melhor biomarcador que possa demonstrar em forma adecuada o risco cardiovascular em um individuo, a correlação, discordância e concordância mostram que é necessário o desenho de um perfil de testes personalizado, com marcadores padronizados e harmonizada, que permite a previsão de risco.

Serum lipids and lipoproteins: a brief review of the composition, transport and physiological functions

The dietary fats are composed primarily of triacylglycerols and some amount of phospholipids and cholesterol. Being hydrophobic in nature, these are insoluble in water, and hence cannot be transported in the blood plasma per se; to enable these lipids to be transported by the blood stream to various peripheral tissues, nature has devised the technique of making these soluble by binding them to proteins. These proteins involved in lipid transport are known as apolipoproteins, and the protein-lipid particle is known as lipoprotein. Thus, lipoproteins can be considered to be the primary transportmechanism to carry lipids from the alimentary tract to various parts of the body. Lipoproteins have gained prominence in medical field over the past few decades because of their role in the aetio-pathogenesis of cardiovascular diseases, principally atherosclerosis which is the cause of coronary artery disease and myocardial infarction. The various types and sub-types of lipoproteins have been found to have differing and even opposing roles in the development of arterial diseases. An understanding of the differing populations of lipoproteins, the associated proteins and other enzymes, and the myriad variety of inter-actions among themselves and with body cells is vital to our understanding the pathways involved in the development of cardio-vascular disordersand in determining the precise steps where pharmacological interventions can be introduced