A rare case of abetalipoproteinemia

The disease studiedhere abetalipoproteinemia (ABL) is a very rare autosomal recessive disorder which is caused by microsomal triglyceride alteration in protein gene mutation. ABL is defined by a lack of lipids and apolipoprotein B in the plasma, as well as fat malabsorption and a variety of clinical symptoms. We report a 21-year-old male with a history of persistent diarrhea, steatorrhea, and growth retardation who was born to consanguineous parents. The patient was diagnosed with ABL and was treated with dietary changes and fat-soluble vitamin replacement, as well as being monitored on an outpatient basis.

The value of serum levels of Apo B/A1, MAP1-LC3 and ICAM-1 in early assessment of acute pancreatitis / 中华急诊医学杂志

Objective:To investigate the early evaluation potential of serum levels of apolipoprotein B/apolipoprotein A1 (Apo B/A1), microtubule-associated protein 1-light chain 3 (MAP1-LC3) and intercellular adhesion molecule-1 (ICAM-1) in acute pancreatitis (AP) patients.Methods:A total of 413 AP patients who were treated at the Second Affiliated Hospital of Anhui Medical University between January 2019 and August 2020 were enrolled. Serum samples were collected from AP patients within 24 h of admission. Patients were divided into the non-severe acute pancreatitis (Non-SAP, n=315) and severe acute pancreatitis (SAP, n=98) groups according to the severity of the disease. Sixty healthy controls were recruited. The differences of serum Apo B/A1, MAP1-LC3 and ICAM-1 among the three groups were compared by one-way analysis of variance, and the correlation between Apo B/A1, MAP1-LC3 and ICAM-1 and the severity of AP was analyzed by Pearson correlation analysis. Sensitivity and specificity in assessing AP severity were predicted by receiver operating characteristic curve (ROC). Results:The early levels of Apo B/A1, MAP1-LC3 and ICAM-1 were all significantly higher for AP patients than for healthy controls ( P<0.05), and the levels of Apo B/A1, MAP1-LC3 and ICAM-1 in SAP patients were significantly higher than those in non-SAP patients[Apo B/A1: 2.21±1.40 vs. (0.96±0.34); MAP1-LC3: 0.92±0.29 vs. (0.48±0.24) ng/mL and ICAM-1: (235.57±54.50 ) vs. (120.28±61.69)ng/mL; P<0.05]. Pearson correlation analysis showed that levels of Apo B/A1, MAP1-LC3 and ICAM-1 were positively correlated with the first Ranson score after admission ( P<0.05), and ICAM-1 showed the highest degree of correlation with AP severity ( r=0.519). Areas under the receiver operating characteristic curve (AUROC) were 0.769 for Apo B/A1, 0.811 for MAP1-LC3, 0.828 for ICAM-1, and 0.938 for combined detection. Conclusions:Serum levels of Apo B/A1, MAP1-LC3 and ICAM-1 within 24 h after admission are significantly correlated with the severity of AP, which has clinical significance for early prediction of the severity of AP.

Apolipoproteína B: sus ventajas en el manejo del riesgo cardiovascular aterosclerótico / Apolipoprotein B: its advantages in the assessment of atherosclerotic cardiovascular risk / Apolipoproteína B: suas vantagens no manejo do risco cardiovascular aterosclerótico

Resumen Se analiza la determinación de apolipoproteína B (Apo B) en la evaluación y tratamiento de la enfermedad cardiovascular aterosclerótica (ECVA) con respecto a tres aspectos: a) marcador de riesgo aterogénico; b) ventajas sobre los lípidos; c) utilidad en el laboratorio bioquímico. Apo B participa en la aterogénesis. Habitualmente las partículas lipoproteicas aterogénicas se evalúan por su contenido en colesterol pero su masa por partícula es muy variable. Sin embargo, cada partícula tiene una molécula de Apo B por lo que es un estimador de su número y marcador de riesgo. Apo B desempeña un rol causal y explica mejor que el colesterol LDL (C-LDL) la relación etiológica con la enfermedad, tiene mayor capacidad discriminante que los lípidos, agregación familiar y mejor parámetro para el manejo del tratamiento en presencia de C-LDL<70 mg/dL, hipertrigliceridemia moderada, síndrome metabólico, obesidad y diabetes. Puede determinarse sin ayuno previo con trazabilidad respecto de un patrón de referencia, comparabilidad y armonía de los resultados entre los laboratorios y menor error analítico que el colesterol no-HDL. C-LDL sigue siendo el objetivo primario para la evaluación y tratamiento del riesgo aterogénico. Por consenso se han informado los valores de corte para Apo B según categorías de riesgo de ECVA y se recomendó su uso cuando sea posible determinarla. Apo B es un excelente marcador de riesgo aterogénico, presenta mayor exactitud y precisión que los lípidos y su inclusión en el manejo de casos clínicos específicos contribuye a mejorar la calidad del tratamiento.

Abstract The determination of apolipoprotein B (Apo B) in the evaluation and treatment of atherosclerotic cardiovascular disease (ACVD) is analyzed, referring to three aspects: a) marker of atherogenic risk; b) advantages over lipids; c) utility in the biochemical laboratory. Apo B participates in atherogenesis. Atherogenic lipoprotein particles are usually evaluated for their cholesterol content, but their mass per particle is highly variable. However, each particle has an Apo B molecule so it is an estimator of its number and a marker of risk. Apo B plays a causal role and explains better than LDL cholesterol (LDL-C) the etiological relationship with the disease; it has a greater discriminating capacity than lipids, family aggregation and it is a better parameter for the management of treatment in the presence of LDL-C<70 mg/dL, moderate hypertriglyceridemia, metabolic syndrome, obesity, and diabetes. It can be determined without prior fasting with traceability to a reference standard, comparability and harmony of results between laboratories and lower analytical error than non-HDL cholesterol. LDL-C remains the primary endpoint for the evaluation and treatment of atherogenic risk. By consensus, cut-off values for Apo B have been reported according to ACVD risk categories and its use was recommended when it is possible to determine it. Apo B is an excellent marker of atherogenic risk, it has greater accuracy and precision than lipids and its inclusion in the management of specific clinical cases contributes to improving the quality of treatment.

Resumo A determinação da apolipoproteína B (Apo B) na avaliação e tratamento da doença cardiovascular aterosclerótica (DCVA) é analisada, referindo-se a três aspectos: a) marcador de risco aterogênico; b) vantagens sobre os lipídios; c) utilidade no laboratório bioquímico. Apo B participa da aterogênese. As partículas de lipoproteína aterogênica são geralmente avaliadas quanto ao seu conteúdo de colesterol, mas sua massa por partícula é altamente variável. No entanto, cada partícula possui uma molécula de Apo B, por isso é um estimador de seu número e um marcador de risco. A Apo B tem papel causal e explica melhor que o colesterol LDL (C-LDL) a relação etiológica com a doença, tem maior capacidade discriminante que os lipídios, agregação familiar e melhor parâmetro para o manejo do tratamento na presença de C-LDL<70 mg/dL, hipertrigliceridemia moderada, síndrome metabólica, obesidade e diabetes. Pode ser determinado sem jejum prévio com rastreabilidade a respeito de um padrão de referência, comparabilidade e harmonia de resultados entre laboratórios e menor erro analítico do que o colesterol não-HDL. O C-LDL continua sendo o objetivo primário para a avaliação e tratamento do risco aterogênico. Por consenso, os valores de corte da Apo B foram reportados de acordo com as categorias de risco de DCVA e seu uso foi recomendado quando possível. A Apo B é um excelente marcador de risco aterogênico, possui maior acurácia e precisão que os lipídeos e sua inclusão no manejo de casos clínicos específicos contribui para a melhoria da qualidade do tratamento.

Association of HDL-Cholesterol Level and ApoB/ApoA Ratio with Coronary Artery Disease Severity and Type 2 Diabetes Mellitus.

The ApoB/ApoA-I ratio reflects the balance between pro- and anti-atherogenic particles, all of which contain cholesterol. The ApoB/A ratio is valid in both genders of all ages and is independent of the lipid levels and phenotypes. This study has been designed to investigate the association between the ratio of apolipoprotein B (apo B)/ apolipoprotein A1 (apo A1) and HDL-C with severity of coronary artery disease in patients with and without type 2 diabetes mellitus.METHODSThe present case control study was carried out in departments of Cardiology and Biochemistry, Vinayaka Missions Hospital, Salem. Fasting blood samples have been collected from 109 CAD patients and 71 control subjects. Serum lipids were measured enzymatically, ApoA-I and Apo B were analysed by immunoturbidimetric method. The study was approved by ethics committee and informed consent was obtained.RESULTSIn our study, Apo A-1 level was significantly low (1.187±0.20) and Apo B was found to be significantly high (1.64±0.62) in CAD with diabetes subjects, when compared to CAD without diabetes. HDL level was found to be significantly lowered in CAD patients. A significant positive association was observed between ApoA-1 and lipid parameters in CAD subjects with HDL-C at (p= 0.00).CONCLUSIONSApo B/Apo A1 ratio may be a healthier forecaster than conventional lipid markers to explore the severity of CAD. This study suggests that instead of measurement of lipid profiles alone, a better indicator apo B, A-I and B/A-I ratio measurement, which in turn highlights the cholesterol balance, can reduce the delay in the recognition of CAD.

Dietary and Blood Lipids in Cardiovascular Disease

Blood lipids are essential for life; at the same time, elevated or reduced levels of some of the components of lipid are related to risk of atherosclerotic cardiovascular disease (ASCVD).This article provides a review on dietary and blood lipids with their impact on cardiovascular health. The role of apolipoprotein B (ApoB), Lipoprotein(a) ((Lp(a))and other lipoprotein particles in the development of ASCVD has been reviewed. There are newevidences that ApoB the structural protein of most of the lipoprotein particles (carrier of blood lipids), in addition to low density lipoprotein-cholesterol (LDL-C), plays a central role in the pathogenesis of atherosclerosis with increased risk for ASCVD. Elevated levels of Lp(a) concentrations are associated with an increased risk of ASCVD, but it appears to be a weaker risk factor than ApoB or LDL-C

The APOB rs693 polymorphism impacts the lipid profile of Brazilian older adults

The apolipoprotein B (APOB) gene contains several polymorphic sites described as risk modifiers for cardiovascular events. The objective of this study was to verify the association of the classic APOB Xba I polymorphism (rs693) with atherosclerotic risk factors in a segment of the Brazilian elderly population considering their usual dietary intake. Clinical and biochemical characteristics as well as total caloric and fat intake data were determined from 644 elderly individuals. Polymorphism analysis was performed by conventional polymerase chain reaction followed by enzyme restriction. Statistical analyses compared measures and proportions according to different APOB genotypic combinations. Statistically significant association was found between Xba I polymorphism and serum LDL, total cholesterol, and total lipid levels, with important elevations among T homozygotes compared to the other genotypes. There was homogeneity in all other parameters analyzed (including intake pattern), with a tendency for reduced levels of circulating apolipoprotein B among TT individuals. Our results pointed out that genetic variation in APOB affected the lipemic profile of elderly individuals in a context not biased by diet, generating a pattern suggestive of secretory disorder of lipoprotein particles, with possible implication in atherosclerotic risk.

Correlation between Pretreatment Serum Apolipoprotein Level and Prognosis of Small Cell Lung Cancer Patients / 中国肺癌杂志

BACKGROUND@#Lung cancer is the leading cause of cancer-related death, and small cell lung cancer (SCLC) has a poor prognosis in all types of lung cancer. This study evaluated the relationship between pretreatment serum apolipoprotein levels and prognosis in patients with SCLC, seeks a new index can guide diagnosis and treatment of SCLC.@*METHODS@#This study retrospectively analyzed the clinical data of 122 patients with SCLC. The clinical results of patients with serum apolipoprotein levels within 2 weeks before treatment were collected, including apolipoprotein AI (ApoA-I), apolipoprotein B (ApoB), and the ratio of apolipoprotein B to apolipoprotein AI (ApoB/ApoA-I). Patients' progression-free survival (PFS) and overall survival (OS) are the main outcome indicators. The best critical to determine the index's value by X-tile tool. For survival analysis, Kaplan-Meier method was used for analysis, and Cox regression analysis method was used for single factor analysis and multifactor analysis.@*RESULTS@#Compared with patients with low ApoA-I levels, patients with high ApoA-I levels (ApoA-I>1.12 g/L) had better OS (21.5 mon vs 12.3 mon, P=0.007) and PFS (7.3 mon vs 5.5 mon, P=0.017). In contrast, patients with higher ApoB/ApoA-I levels had worse median OS than patients with lower ApoB/ApoA-I levels (13.4 mon vs 20.7 mon, P=0.012). Multivariate Cox regression analysis showed that ApoA-I was an independent prognostic factor affecting PFS in SCLC patients (HR=0.67, 95%CI: 0.45-0.99, P=0.043). ApoB/ApoA-I is an independent risk factor for OS in patients with SCLC (HR=1.98, 95%CI: 1.21-3.23, P=0.007).@*CONCLUSIONS@#Serum ApoA-I level and ApoB/ApoA-I level before treatment can be important prognostic factors for SCLC, which is helpful to judge the prognosis of patients.

Small interfering RNA for cancer treatment: overcoming hurdles in delivery

In many ways, cancer cells are different from healthy cells. A lot of tactical nano-based drug delivery systems are based on the difference between cancer and healthy cells. Currently, nanotechnology-based delivery systems are the most promising tool to deliver DNA-based products to cancer cells. This review aims to highlight the latest development in the lipids and polymeric nanocarrier for siRNA delivery to the cancer cells. It also provides the necessary information about siRNA development and its mechanism of action. Overall, this review gives us a clear picture of lipid and polymer-based drug delivery systems, which in the future could form the base to translate the basic siRNA biology into siRNA-based cancer therapies.

Effect of viral macrophage inflammatory protein Ⅱ on the expression of APOBEC3G in 293T cells / 中华皮肤科杂志

Objective@#To assess the effect of viral macrophage inflammatory protein (vMIP) -Ⅱ on the expression of apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G) , and to explore the mechanisms.@*Methods@#A recombinant plasmid pEGFP-N3-K4 (vMIP-Ⅱ plasmid group) and an empty plasmid pEGFP-N3 (empty plasmid group) were separately transfected into 293T cells, and quantitative PCR and Western blot analysis were performed to evaluate the effect of transfection with vMIP-Ⅱ gene on the APOBEC3G expression in 293T cells. Some 293T cells in the empty plasmid group and vMIP-Ⅱ plasmid group were treated with 1 000 IU/ml interferon (IFN) -α for 36 hours, and then Western blot analysis was conducted to determine the APOBEC3G expression in the empty plasmid group and vMIP-Ⅱ plasmid group with or without IFN-α treatment. Some 293T cells transfected with vMIP-Ⅱ plasmids were treated with 75 μmol/L AG490 (a JAK/STAT signaling pathway inhibitor) and 20 μmol/L U0126 (an ERK signaling pathway inhibitor) separately; after 24 hours, total protein was extracted from 293T cells, and Western blot analysis was conducted to determine the expression of APOBEC3G. A recombinant plasmid containing APOBEC3G promoter was constructed by using a luciferase reporter gene, and the promoter fragment included the full-length promoter sequence (POS) of APOBEC3G, sequences with the lengths of 1 560, 960, 720, 480, 420, 360, 330 and 240 bp, and the regulatory element-free region (NEG) of APOBEC3G, separately. Some 293T cells were co-transfected with the recombinant plasmid carrying luciferase reporter gene and vMIP-Ⅱ plasmid (experimental group), or the recombinant plasmid and empty plasmid (control group). Subsequently, the activity of the APOBEC3G promoter was evaluated, and the key promoter region through which the transcriptional activity of APOBEC3G was regulated by vMIP-Ⅱ was analyzed. Statistical analysis was carried out by using t test, one-way analysis of variance and least significant difference (LSD) -t test.@*Results@#The mRNA and protein expression of APOBEC3G was significantly higher in the vMIP-Ⅱ plasmid group (2.500 ± 0.013, 1.472 ± 0.013 respectively) than in the control group (1, 0.364 ± 0.030 respectively; t = 6.22, 6.54 respectively, both P < 0.05) . The APOBEC3G expression significantly differed among the empty plasmid group, vMIP-Ⅱ plasmid group, empty plasmid + IFN-α group and vMIP-Ⅱ plasmid + IFN-α group (1, 2.030 ± 0.108, 2.700 ± 0.081 and 2.600 ± 0.099 respectively; F = 67.026, P < 0.001) , but there was no significant difference between the vMIP-Ⅱ plasmid group and empty plasmid + IFN-α group (t = 3.46, P > 0.05) . The APOBEC3G expression also significantly differed among the vMIP-Ⅱ plasmid group, vMIP-Ⅱ plasmid + AG490 group and vMIP-Ⅱ plasmid + U0126 group (0.617 ± 0.025, 0.179 ± 0.061, 0.359 ± 0.012 respectively; F = 70.019, P < 0.001) , and was significantly lower in the vMIP-Ⅱ plasmid + AG490 group and vMIP-Ⅱ plasmid + U0126 group than in the vMIP-Ⅱ plasmid group (t = 9.66, 11.836 respectively, both P < 0.01) . Luciferase activity assay showed that the promoter activity significantly differed among the vMIP-Ⅱ plasmid groups transfected with POS, 1 560-, 960-, 720-, 480-, 420-, 360-, 330-, 240-bp or NEG sequences (F = 81.092, P < 0.001) , and the APOBEC3G promoter activity decreased greatly from the 720-bp group to 480-bp group.@*Conclusion@#vMIP-Ⅱ upregulates the expression of APOBEC3G, likely through the JAK/STAT signaling pathway or the key promoter region regulating the transcriptional activity of APOBEC3G.

Ablation of gut microbiota alleviates obesity-induced hepatic steatosis and glucose intolerance by modulating bile acid metabolism in hamsters

Since metabolic process differs between humans and mice, studies were performed in hamsters, which are generally considered to be a more appropriate animal model for studies of obesity-related metabolic disorders. The modulation of gut microbiota, bile acids and the farnesoid X receptor (FXR) axis is correlated with obesity-induced insulin resistance and hepatic steatosis in mice. However, the interactions among the gut microbiota, bile acids and FXR in metabolic disorders remained largely unexplored in hamsters. In the current study, hamsters fed a 60% high-fat diet (HFD) were administered vehicle or an antibiotic cocktail by gavage twice a week for four weeks. Antibiotic treatment alleviated HFD-induced glucose intolerance, hepatic steatosis and inflammation accompanied with decreased hepatic lipogenesis and elevated thermogenesis in subcutaneous white adipose tissue (sWAT). In the livers of antibiotic-treated hamsters, cytochrome P450 family 7 subfamily B member 1 (CYP7B1) in the alternative bile acid synthesis pathway was upregulated, contributing to a more hydrophilic bile acid profile with increased tauro--muricholic acid (TMCA). The intestinal FXR signaling was suppressed but remained unchanged in the liver. This study is of potential translational significance in determining the role of gut microbiota-mediated bile acid metabolism in modulating diet-induced glucose intolerance and hepatic steatosis in the hamster.

Correlation between ratio of Apo A1／Apo B and heart failure／ / 心血管康复医学杂志

To analyze the correlation between ratio of apolipoprotein A 1 (ApoA1 )／apolipoprotein B (ApoB) and heart failure (HF).Methods : A total of 150 HF patients treated in our department were divided into NYHA class II group (n＝54) ,class III group (n＝48) and class IV group (n＝48).Their LVEF ,stroke volume (SV) ,cardiac output (CO) ,cardiac index (CI) ,levels of BNP ,serum Apo A1 and Apo B were measured ,and Apo A1／Apo B was calculated ,then correlation analysis was performed .Results : Compared with class II group ,there were significant reductions in LVEF [ (37. 29 ± 6. 25)% vs.(34. 66 ± 5.90)% vs.(32.55 ± 5. 23)%] ,SV [ (36. 40 ± 4.18) ml vs .(34.05 ± 3. 49) ml vs.(31.72 ± 5.44) ml] ,CO [ (3.71 ± 0.59) L／min vs .(3.39 ± 0. 43) L／min vs.(3. 17 ± 0.44) L／min] ,CI [ (2. 16 ± 0.50 ) L· min－1 · m－2 vs.(1. 76 ± 0.37 ) L· min－1 · m－2 vs.(1. 44 ± 0.43) L·min－1 ·m－2 ] ,and ApoA1／ApoB [ (1.17 ± 0.44) vs.(0. 98 ± 0.28) vs.(0. 65 ± 0.24)] in class III group and class IV group ,and those of class IV group were significantly lower than those of class III group ;significant rise in levels of plasma BNP [ (469.23 ± 63. 12) pg／ml vs.(612. 52 ± 80.34) pg／ml vs.(822.96 ± 97.22) pg／ml] in class III group and class IV group ,and those of class IV group were significantly higher than those of class III group ,P＜0.05 or ＜0.01. Pearson correlation analysis indicated that serum Apo A 1／Apo B was significant positively correla‐ted with LVEF ,SV ,CO and CI ( r＝0. 422～0. 603 , P＜0.05 or ＜0.01) ,and significant inversely correlated with plasma BNP level ( r＝ －0. 625 , P＝0.002).Conclusion :The worse the cardiac function is ,the lower serum Apo A1／Apo B is in HF patients .There is positive correlation between them .21－3

Effect of viral macrophage inflammatory protein Ⅱ on the expression of APOBEC3G in 293T cells / 中华皮肤科杂志

Objective To assess the effect of viral macrophage inflammatory protein (vMIP)-Ⅱ on the expression of apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G),and to explore the mechanisms.Methods A recombinant plasmid pEGFP-N3-K4 (vMIP-Ⅱ plasmid group) and an empty plasmid pEGFP-N3 (empty plasmid group) were separately transfected into 293T cells,and quantitative PCR and Western blot analysis were performed to evaluate the effect of transfection with vMIP-]Ⅱ gene on the APOBEC3G expression in 293T cells.Some 293T cells in the empty plasmid group and vMIP-Ⅱ plasmid group were treated with 1 000 IU/ml interferon (IFN)-α for 36 hours,and then Western blot analysis was conducted to determine the APOBEC3G expression in the empty plasmid group and vMIP-Ⅱ plasmid group with or without IFN-α treatment.Some 293T cells transfected with vMIP-Ⅱplasmids were treated with 75 μ mol/L AG490 (a JAK/STAT signaling pathway inhibitor) and 20 μ mol/L U0126 (an ERK signaling pathway inhibitor) separately;after 24 hours,total protein was extracted from 293T cells,and Western blot analysis was conducted to determine the expression of APOBEC3G.A recombinant plasmid containing APOBEC3G promoter was constructed by using a luciferase reporter gene,and the promoter fragment included the full-length promoter sequence (POS) of APOBEC3G,sequences with the lengths of 1 560,960,720,480,420,360,330 and 240 bp,and the regulatory element-free region (NEG) of APOBEC3G,separately.Some 293T cells were co-transfected with the recombinant plasmid carrying luciferase reporter gene and vMIP-Ⅱ plasmid (experimental group),or the recombinant plasmid and empty plasmid (control group).Subsequently,the activity of the APOBEC3G promoter was evaluated,and the key promoter region through which the transcriptional activity of APOBEC3G was regulated by vMIP -Ⅱ was analyzed.Statistical analysis was carried out by using t test,one-way analysis of variance and least significant difference (LSD)-t test.Results The mRNA and protein expression of APOBEC3G was significantly higher in the vMIP-Ⅱ plasmid group (2.500 ± 0.013,1.472 ± 0.013 respectively) than in the control group (1,0.364 ± 0.030 respectively;t =6.22,6.54 respectively,both P ＜ 0.05).The APOBEC3G expression significantly differed among the empty plasmid group,vMIP-Ⅱ plasmid group,empty plasmid + IFN-oα group and vMIP-Ⅱ plasmid + IFN-α group (1,2.030 ± 0.108,2.700 ± 0.081 and 2.600 ± 0.099 respectively;F =67.026,P ＜ 0.001),but there was no significant difference between the vMIP-Ⅱ plasmid group and empty plasmid + IFN-α group (t =3.46,P ＞ 0.05).The APOBEC3G expression also significantly differed among the vMIP-Ⅱ plasmid group,vMIP-Ⅱ plasmid + AG490 group and vMIP-Ⅱplasmid + U0126 group (0.617 ± 0.025,0.179 ± 0.061,0.359 ± 0.012 respectively;F =70.019,P ＜ 0.001),and was significantly lower in the vMIP-Ⅱ plasmid + AG490 group and vMIP-Ⅱ plasmid + U0126 group than in the vMIP-Ⅱ plasmid group (t =9.66,11.836 respectively,both P ＜ 0.01).Luciferase activity assay showed that the promoter activity significantly differed among the vMIP-Ⅱ plasmid groups transfected with POS,1 560-,960-,720-,480-,420-,360-,330-,240-bp or NEG sequences (F =81.092,P ＜ 0.001),and the APOBEC3G promoter activity decreased greatly from the 720-bp group to 480-bp group.Conclusion vMIP-Ⅱ upregulates the expression of APOBEC3G,likely through the JAK/STAT signaling pathway or the key promoter region regulating the transcriptional activity of APOBEC3G.

Rol del enterocito en la dislipidemia de la diabetes mellitus tipo 2 / Role of the enterocyte in type 2 diabetes mellitus associated dyslipidemia

En la diabetes mellitus tipo 2 el aumento en la producción de quilomicrón en el estado post-prandial se asocia a mayor riesgo cardiovascular. La evidencia actual posiciona al enterocito como actor principal en la dislipemia de la diabetes mellitus tipo 2 debido a que aumenta la producción de apolipoproteína B-48 en respuesta a una elevación de ácidos grasos libres y glucosa. El metabolismo del quilomicrón se encuentra regulado por múltiples factores independientes además de la ingesta de grasa alimentaria. Entre estos factores se destacan las hormonas intestinales, como el péptido similar al glucagón tipo 1 que disminuye la producción de apolipoproteína B-48 y el péptido similar al glucagón tipo 2 que la aumenta. Por otro lado, la insulina inhibe de forma aguda la producción de quilomicrón en el sujeto sano mientras que en la diabetes mellitus tipo 2, este efecto está ausente. La comprensión de los factores reguladores emergentes de la secreción de quilomicrón permite vislumbrar nuevos mecanismos de control en su metabolismo y aportar estrategias terapéuticas focalizadas en la hiperlipidemia posprandial en la diabetes mellitus tipo 2 con la reducción del riesgo cardiovascular.

In type 2 diabetes mellitus there is an overproduction of chylomicron in the postprandial state that is associated with increased cardiovascular risk. Current evidence points out a leading role of enterocyte in dyslipidemia of type 2 diabetes mellitus, since it increases the production of apolipoprotein B-48 in response to a raise in plasma free fatty acids and glucose. The chylomicron metabolism is regulated by many factors apart from ingested fat, including hormonal and metabolic elements. More recently, studies about the role of gut hormones, have demonstrated that glucagon-like peptide-1 decreases the production of apolipoprotein B-48 and glucagon-like peptide-2 enhances it. Insulin acutely inhibits intestinal chylomicron production in healthy humans, whereas this acute inhibitory effect on apolipoprotein B-48 production is blunted in type 2 diabetes mellitus. Understanding these emerging regulators of intestinal chylomicron secretion may offer new mechanisms of control for its metabolism and provide novel therapeutic strategies focalized in type 2 diabetes mellitus postprandial hyperlipidemia with the reduction of cardiovascular disease risk.

Apolipoprotein B and angiotensin-converting enzyme polymorphisms and aerobic interval training: randomized controlled trial in coronary artery disease patients

Physical training has been strongly recommended as a non-pharmacological treatment for coronary artery disease (CAD). Genetic polymorphisms have been studied to understand the biological variability in response to exercise among individuals. This study aimed to verify the possible influence of apolipoprotein B (ApoB: rs1042031 and rs693) and angiotensin-converting enzyme (ACE-ID: rs1799752) genotypes on the lipid profile and functional aerobic capacity, respectively, after an aerobic interval training (AIT) program in patients with CAD and/or cardiovascular risk factors. Sixty-six men were randomized and assigned to trained group (n=32) or control group (n=34). Cardiopulmonary exercise test was performed to determine the ventilatory anaerobic threshold (VAT) from cardiorespiratory variables. The AIT program, at an intensity equivalent to %VAT (70-110%), was conducted three times a week for 16 weeks. ApoB gene polymorphisms (−12669C>T (rs1042031) and −7673G>A (rs693)) were identified by real-time polymerase chain reaction (PCR). I/D polymorphism in the ACE gene (rs1799752) was identified through PCR and fragment size analysis. After 16 weeks, low-density lipoprotein (LDL) levels increased in the trained and control groups with the GA+AA genotype (−7673G>A) of the ApoB gene. Trained groups with ACE-II and ACE-ID genotypes presented an increase in oxygen consumption (VO2VAT) and power output after the AIT program. The presence of the ACE I-allele was associated with increased aerobic functional capacity after the AIT program. Increased LDL levels were observed over time in patients with the −7673G>A polymorphism of the ApoB gene. Trial Registration Information: ClinicalTrials.gov: NCT02313831

Clinical significance of apolipoprotein B/apolipoprotein A1 ratio detection for patients with polycystic ovary syndrome combined with metabolic syndrome / 中华内分泌外科杂志

Objective To study the clinical significance of apolipoprotein B and apolipoprotein A1 ratio (ApoB/ApoA1) in patients with polycystic ovary syndrome (PCOS) combined metabolic syndrome (MS),by detecting the level of ApoB and ApoA1 in patients' serum.Methods 160 patients with PCOS were selected in our hospital from Jan.2014 to Dec.2015,and they were divided into MS group and non-MS group according to the diagnostic criteria of MS.The anthropometric measurements,endocrine markers,glucose and lipid metabolism indexes of patients in the two groups were measured and compared.Correlation of ApoB/ApoA 1 ratio and components of MS were analyzed,respectively.Relationship between ApoB/ApoA1 ratio and the number of abnormal components in MS were also investigated.Results Significant difference was found in the levels of ApoB ((1.01±0.34) g/L) and ApoA1((1.15±0.29) g/L) between MS group and non-MS group (P＜0.05),and ApoB/ApoA1 ratio in MS group was obviously higher than that in non-MS group (P＜0.05).ApoB/ApoAl ratio was positively correlated with BMI,waist circumference (WC),systolic blood pressure (SBP),diastolic blood pressure (DBP),fasting plasma glucose (FPG),insulin resistance index (HOMA-IR),high triglycerides (TG) and low density lipoprotein (LDL-C),respectively,and it was negatively correlated with high density lipoprotein (HDL-C)(P＜0.05).However,there was no significant correlation between ApoB/ApoA1 ratio and the age,fasting insulin (FINS),as well as the total cholesterol (TC) (P＞0.05).Moreover,ApoB/ApoA1 ratio increased with increase in the number of abnormal components (P＜0.05).Conclusion ApoB/ApoA1 ratio is closely related to the components of MS,and it may have important clinical significance for diagnosis of PCOS combined MS and preventing long-term complications of PCOS.

Value of serum 25 hydroxy vitamin D ,homocysteine and apolipoprotein B/A1 in patients with essential hypertension / 国际检验医学杂志

Objective To investigate the value of serum 25 hydroxy vitamin D [25(OH)D] ,homocysteine (Hcy) and apolipoprotein B/A1 in patients with essential hypertension.Methods Totally 191 cases of essen-tial hypertension admitted in the hospital from May 2016 to May 2017 were selected as observation group ,and were divided into hypertension grade 1 group (54 cases) ,hypertension grade 2 group (78 cases) ,hypertension grade 3 group (59 cases) in accordance with the classification of hypertension.54 healthy people who under-went healthy assessment during the same period were selected as the control group.The changes of serum 25 (OH) D ,Hcy and apolipoprotein B/A1 ,and the sensitivity and the specificity of combined detection of 25 (OH)D ,Hcy and apolipoprotein B/A1 were compared.Results The serum 25 (OH) D level in the observa-tion group was lower than that in the control group ,while the levels of Hcy and apolipoprotein B/A1 were higher than those in the control group ,and the differences were statistically significant (P＜0.05).The level of serum 25 (OH) (OH) D in hypertension grade 3 group was lower than those in hypertension grade 2 group and hypertension grade 1 group ,but the levels of Hcy and apolipoprotein B/A1 were higher than those in hy-pertension grade 2 group and hypertension grade 1 group ,and the differencs were statistically significant (P＜0.05) ;the level of serum 25 (OH) D in hypertension grade 2 group was lower than that in hypertension grade 1 group ,but the levels of Hcy and apolipoprotein B/A1 were higher than those in hypertension grade 1 group , and the difference was statistically significant (P＜0.05).The sensitivity and the specificity of combined de- tection of 25 (OH) D ,Hcy and apolipoprotein B/A1 were higher than those of single detection of 25 (OH) D , Hcy and apolipoprotein B/A1.Conclusion Serum 25 (OH) D level decreased in patients with essential hyper-tension ,while Hcy and apolipoprotein B/A1 levels increased ,and the combined detection of 25(OH)D ,Hcy and apolipoprotein B/A1 had high sensitivity and specificity in diagnosis.

Correlation of apolipoprotein AI, apolipoprotein B and their ratio with the severity of cerebral white matter lesions / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the correlation of apolipoprotein AI (ApoAI), ApoB, ApoB/ApoAI and the severity of brain white matter lesions (WML).</p><p><b>METHODS</b>A total of 648 patients with WML confirmed by brain magnetic resonance imaging (MRI) were divided into mild WML group (=386) and moderate to severe WML group (=262) according to evaluations with the Fazekas scale. The demographic data, blood biochemical parameters and the levels of ApoAI, ApoB and ApoB/AI ratio were compared between the two groups to identify the risk factors of moderate to severe WML.</p><p><b>RESULTS</b>Univariate analysis showed that age, gender, hypertension, diabetes, coronary heart disease, previous stroke, homocysteine, HDL-C, ApoAI, and ApoB/AI ratio all differed significantly between the two groups ( < 0.05), but ApoB levels were similar between them ( > 0.05). Multivariate logistic regression analysis revealed that with ApoAI and ApoB/AI ratio as the continuous variables, after adjustment for the compounding factors, ApoB/AI ratio was an independent risk factor (OR=11.456, 95% : 3.622-36.229, < 0.001) and ApoAI was an independent protective factor for moderate to severe WML (OR=0.068, 95% : 0.018-0.262, < 0.001). With the upper quartiles of ApoAI level (1.38 g/L) and ApoB/AI ratio (0.58) as their respective cutoff values, patients with a high ApoAI level and a low ApoB/AI ratio were found to have the lowest incidence of moderate to severe WML ( < 0.001).</p><p><b>CONCLUSIONS</b>An increased ApoB/AI ratio is an independent risk factor and an increased ApoAI level is an independent protective factor for moderate to severe WML.</p>

Association between polymorphisms in the APOB gene and hyperlipidemia in the Chinese Yugur population

We investigated the influence of apolipoprotein B gene (APOB) variants on the risk of hyperlipidemia (HL) in 631 middle-aged and elderly members of the Chinese Yugur population (HL, n=336; normolipidemia, n=295). APOB polymorphisms were identified using mass spectrometry, and five single nucleotide polymorphisms (rs1042034, rs2163204, rs512535, rs676210, and rs679899) and serum lipids were further analyzed. rs1042034 and rs676210 were significantly associated with HL (P<0.05). Compared with the GG or AA genotype, individuals with AG and AG+AA in rs1042034 and with AG and AG+GG in rs676210 had a 1.67-fold (95%CI=1.20-2.33),1.63-fold (95%CI=1.19-2.24), 1.72-fold (95%CI=1.24-2.40), and 1.67-fold (95%CI=1.21-2.291) increased risk of high HL, respectively. rs2163204 was in strong linkage disequilibrium with rs1042034, rs676210, and rs679899, and strong disequilibrium was observed between rs1042034 and rs676210 (D′>0.9). Compared with the GTGAA haplotype, haplotypes ATGGA and ATAGG were more strongly associated with HL [odds ratio (OR)=1.46, 95%CI=0.02-2.11; OR=1.63, 95%CI=1.03-2.60, respectively]. The risk factors age (P=0.008), body mass index (P<0.0001), GA+GG genotype in rs676210 (P=0.009), and alcohol consumption (P=0.056) contributed strongly to HL development. The A allele of rs1042034 and the G allele of rs676210 may thus predispose middle-aged and elderly members of the Chinese Yugur population to HL in combination with other genetic or nutritional factors, and could be used as new genetic markers for HL screening.

The analysis of risk factors and subtypes with CISS classification of minor stroke / 中国神经精神疾病杂志

Objective To investigate the features of risk factors of minor stroke with CISS classification in Guangdong Province. Methods We retrospectively investigated the patients admitted within 3 days of the occurrence of a minor stroke, and were classified by CISS criteria as large artery atherosclerosis (LAA), cardiogenic stroke (CS), penetrating artery disease (PAD), other etiology (OE), undetermined etiology (UE). Results In this study, 303 pa-tients met the inclusion criteria of minor stroke. The highest percentage of the risk factors included hypertension (72.3%), hyperlipidemia (58.3%), and diabetes mellitus (39.9%). Among different subtypes, 41.9% were diagnosed with LAA, and 50.8% with PAD. Plasma triglyceride (TG)(1.765 ±1.18)mg/L vs.(2.19 ±1.84)mg/L,P=0.03], apolipoproteinsB (ApoB) [(0.95±0.29)mg/L vs.(1.11±0.46)mg/L,P=0.009]C-reactive protein (CRP) [(6.63±11.30) mg/L vs.(3.42 ±5.02)mg/L,P=0.042] and ApoB/ApoA1 ratio [(0.754 ±0.25)mg/L vs.(0.875 ±0.49)mg/L,P=0.019], differed significantly between group LAA and PAD. Conclusion Hypertension, hyperlipidemia and diabetes mellitus are the major risk factors of minor stroke. The most common subtypes of the minor stroke patients in Guangdong Province are LAA and PAD, and detecting their TG, apoB, CRP level and apoB/apoA1 ratio might help subclassify minor stroke according to CISS.

Validation of a Newly Developed Equation for Estimating Serum Apolipoprotein B: Associations with Cardiovascular Disease Surrogate Markers in Koreans

PURPOSE: Many clinical guidelines recommend apolipoprotein B (apoB) measurement, particularly in subjects with metabolic syndrome or type 2 diabetes. Recently, we developed a new equation to estimate serum apoB (apoBE). We validated the clinical relevance of apoBE and compared the performance of the equation with conventional lipid measurements and direct measurement of apoB. MATERIALS AND METHODS: Study subjects were recruited from patients who visited the Health Screening Center at Kangbuk Samsung Hospital between January and December 2009 for routine medical examinations (n=78125). For analysis of coronary calcium score, we recruited study subjects from the same institution between January 2007 and December 2010 (n=16493). RESULTS: apoBE was significantly correlated with serum high-sensitivity C-reactive level {r=0.18 [95% confidence interval (CI), 0.18–0.19]} in partial correlation analysis adjusted for age, sex, and body mass index. apoBE was associated with a Framingham risk score indicating more than moderate risk (10-year risk ≥10%), the presence of microalbuminuria, and the presence of coronary artery calcium in multivariate logistic regression analysis. These associations were comparable to those of directly-measured serum apoB [odds ratio per 1 SD 3.02 (2.75–3.27) vs. 2.70 (2.42–3.02) for a Framingham risk score indicating more than moderate risk, 1.31 (1.21–1.41) vs. 1.35 (1.25–1.45) for the presence of microalbuminuria, and 1.33 (1.26–1.41) vs. 1.31 (1.23–1.38) for the presence of coronary calcium score respectively]. These findings were also consistently observed in subgroup analysis for subjects with type 2 diabetes. CONCLUSION: The associations between cardiovascular surrogate markers and apoBE were comparable to those of directly-measured apoB.