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.

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.

Effect of Shouwu Jiangzhi decoction on hyperlipidemia Golden Syrian hamsters based on TNF-α/MAPK/apoB-48 pat / 中国药科大学学报

@#To investigate the mechanism of Shouwu Jiangzhi decoction in treatment of hyperlipidemia by suppress apoB-48 in small intestines, Golden Syrian hamsters were randomly devided into blank group, model group, fenobrate treatment group and Shouwu Jiangzhi decoction treatment group based on weight. The hyperlipidemia models of golden Syrian hamsters were induced by high fat diet(HFD)treatment for 4 weeks, then administered orally with drugs for 4 weeks. The serum indexes of HDL-C, LDL-C, TG and TC were determined by microplate methods, ELISA kits were used to evaluate the contents of serum TNF-α, apoB-48 and FFA. The protein expression levels of p38, ERK, JNK, SREBP, TNF-α and apoB-48 in small intestines were determined by Western blots. The results showed that Shouwu Jiangzhi decoction can effectively increase the serum HDL-C level and reduce the serum level of TG, LDL-C, TNF-α and apoB-48 in HFD-induced hamsters. Furthermore, Shouwu Jiangzhi decoction can significantly downregulate the protein expressions of p38, JNK, ERK, SREBP, TNF-α and apoB-48 in small intestines. Results above indicate that Shouwu Jiangzhi decoction may downregulate the protein expression of apoB-48 to treat hyperlipidemia via partially downregulating TNF-α/MAPK signal pathway.

Ultrassequenciamento exômico dos principais genes relacionados com a hipercolesterolemia familial / Ultrasequensing exomic of the main genes related to familial hypercholesterolemia

A frequência de Hipercolesterolemia Familial (HF) ainda é desconhecida no Brasil, principalmente pela ausência de estudos com caracterização genotípica associada à fenotípica. Os dados epidemiológicos existentes se baseiam apenas no fenótipos e carecem do diagnóstico molecular confirmatório. O objetivo do presente estudo foi identificar as principais causas genéticas da HF em pacientes diagnosticados fenotipicamente através de um painel exômico com 61 genes a fim de contribuir para um sistema de confirmação do diagnostico molecular em uma amostra da população brasileira. Para isso foram incluídos 141 pacientes, não aparentados, portadores de HF atendidos pelo setor de dislipidemias do Instituto Dante Pazzanese de Cardiologia, Laboratório de Analises Clinicas da Faculdade de Ciências Farmacêuticas da Universidade Federal do Rio Grande do Norte e do Programa Hipercol Brasil do Instituto do Coração. As amostras de sangue periférico foram obtidas para determinações fenotípicas laboratoriais e extração de DNA genômico. A biblioteca de DNA foi construída utilizando o kit Nextera® Rapid Capture Enrichment Custom enriquecendo os éxons de 61 genes que direta ou indiretamente estão relacionados com metabolismo do colesterol. O ultrassequenciamento foi realizado utilizando kit MiSeq Reagent (300 a 500 ciclos) na plataforma MiSeq (Illumina). Os resultados de sequenciamento foram inicialmente alinhados a uma sequência referência e analisados para eliminação de falsos positivos, segundo os parâmetros de qualidade, tais como: cobertura mínima de 30x, frequência do alelo alterado maior que 20% e diferença da distribuição das leituras entre as sequências nucleotídicas menor que 15%. Foram identificadas 472 diferentes variantes em 56 dos genes presentes no painel, sendo 45 consideradas como não descritas. Nos genes APOA1, APOA2, LIPC, RBP4 e TIMP1 não foram observadas variantes dentro dos critérios estabelecidos. Das variantes observadas 25 identificadas em 30 (21,2%) pacientes já tinha sido publicadas em relação à HF nos três principais genes (LDLR, APOB e PCSK9), confirmando o diagnóstico. Foi caracterizado genotipicamente outras dislipidemias primárias em 7 pacientes, sem diagnóstico molecular de HF, através de variantes identificadas no ultrassequenciamento em outros genes. Dos 104 pacientes que não possuíam nenhuma variante já previamente caracterizada, 69 possuíam variantes relacionados com o metabolismo do colesterol. As variantes sem patogenicidade conhecida foram avaliadas através de ferramentas de predição in silico e 22 delas possuíam características sugestivas de patogenicidade em pelo menos 4 das ferramentas utilizadas, duas delas também mostraram alterar a estrutura da proteína segundo análises de docking molecular. Foram identificadas também 223 variantes em região não transcritas (UTR). Quando realizada as análises estatística de todas as variantes identificadas, observamos associação de 13 variantes com concentrações mais elevadas de colesterol da LDL, 5 com concentrações mais elevadas de apolipoproteina B-100, 5 com concentrações mais elevadas de colesterol total, 6 com presença de arco córneo, 2 com manifestação de xantelasmas, 2 com ausência de xantomas e 3 com a presença de doença arterial coronariana. Dessas 6 variantes já haviam sido previamente descritas com HF ou algum outro fenótipo associado e 2 não tinham citação na literatura pesquisada, mas possuíam característica patogênica para a proteína segundo as ferramentas de predição in silico. Este estudo permitiu a identificação das causas genéticas da HF em pacientes brasileiros diagnosticados fenotipicamente, mostrando que a técnica escolhida permitiu caracterizar 21,2% dos pacientes. Além disso, foi possível identificar outras dislipidemias primárias e caracterizar algumas variantes que, apesar de necessitarem serem validadas, indicam uma possível associação com a HF, aumentando o esclarecimento do fenótipo com o genótipo para 74,5%. Este estudo também possibilitou a identificação de novas variantes que devem ser avaliadas para confirmar associação com a doença e utilizar para o diagnóstico propondo um novo painel poligênico

The frequency of Familial Hypercholesterolemia (FH) is still unknown in Brazil, mainly due to the absence of studies with genotypic characterization associated with phenotype. Existing epidemiological data are based only on the phenotypes and lack the confirmatory molecular diagnosis. The aim of the present study was to identify main genetic causes of FH in patients diagnosed phenotypically through an exomic panel with 61 genes in order to contribute to a system of confirmation molecular diagnosis in a sample of the Brazilian population. To this end, 141 non-related patients with FH treated by the dyslipidemia sector of the Institute Dante Pazzanese of Cardiology, Clinical Analysis Laboratory of the Faculty of Pharmaceutical Sciences of the University Federal of Rio Grande do Norte and the Hipercol Brazil Program of the Heart Institute. Peripheral blood samples were obtained for laboratory phenotypic determinations and extraction of genomic DNA. The DNA library was constructed using the Nextera® Rapid Capture Enrichment Custom kit, enriching with éxons of 61 genes that are directly or indirectly related to cholesterol metabolism. Ultrasequencing was performed using MiSeq Reagent kit (300 to 500 cycles) on the MiSeq platform (Illumina). The sequencing results were initially aligned to a reference sequence and analyzed for false positive elimination according to quality parameters such as: minimum coverage of 30x, altered allele frequency greater than 20%, and difference in the distribution of reads between sequences nucleotides less than 15%. 472 different variants were identified in 56 of the genes present in the panel, of which 45 were considered not described. In the APOA1, APOA2, LIPC, RBP4 and TIMP1 genes no variants were observed within the established criteria. In 25 of the variants observed presents in 30 (21.2%) patients had already been published in relation to FH in the three main genes (LDLR, APOB and PCSK9), confirming the diagnosis. Other primary dyslipidemias were caracterized genotypically in 7 patients, without molecular diagnosis of HF, through variants identified in ultrasequencing in other genes. Of the 104 patients who did not have any previously characterized variant, 69 had variants related to cholesterol metabolism. The variants without known pathogenicity were evaluated using in silico prediction tools and 22 of them had characteristics suggestive of pathogenicity at least 4 of the tools used, two of them also showed to alter the structure of the protein according to molecular docking analyzes. Were also identified 223 non-transcribed region (UTR) variants. Statistical analysis of all the variants identified showed association of 13 variants with higher concentrations of LDL cholesterol, 5 with higher concentrations of apolipoprotein B-100, 5 with higher concentrations of total cholesterol, 6 with presence of an arc corneal, 2 with manifestation of xanthelasms, 2 with absence of xanthomas and 3 with the presence of coronary artery disease. Of these 6 variants had previously been described with HF or some other associated phenotype and 2 had no citation in the researched literature, but had a pathogenic characteristic for the protein according to in silico prediction tools. This study allowed the identification of the genetic causes of FH in Brazilian patients diagnosed phenotypically, showing that the technique chosen allowed to characterize 21.2% of the patients. In addition, it was possible to identify other primary dyslipidemias and to characterize some variants that, although they need to be validated, indicate a possible association with HF, increasing the clarification of the phenotype with the genotype to 74.5%. This study also allowed the identification of new variants that should be evaluated to confirm association with the disease and to use for the diagnosis proposing a new polygenic panel

Clinical Implication of ApoB (12669G/A) Gene Polymorphism and Risk of Cardio Vascular Disease in Indian Population

Background: Cardiovascular disease is rising day by day due to having high fat diet and due to genetic alterations. Materials & Methods: Study included 70 CVD patients and their peripheral blood samples were collected for genotyping by venipuncture under aseptic condition in EDTA vials (2ml) as well as in serum vials (3ml) for biochemical parameters. Genomic DNA extraction was done by phenol chloroform method from blood samples collected in EDTA vials from cases as well as controls for genotype study. Results: The difference of genotype between cases and controls was found to be significant (p=0.0003). Study observed that high percentage of GA 29 (41.4%) and AA 8 (11.4%) genotype was found in patients compared to controls GA 10 (20%) and AA 0 (0%) while lower GG 33 (47.2%) genotype in patients compared to control GG 40 (80%) genotype. Compared to the GG genotype, the OR 3.51 (1.49-8.25) and 20.55 (1.14-369.6) for the heterozygous GA and homozygous AA genotypes were estimated, suggesting a possible dominant effect of Apo B polymorphism on CVD risk. In smokers, compared to the GG genotype, the OR 2.19 (0.69-6.88) and 1.71 (0.29-9.87) for the heterozygous GA and homozygous AA genotypes. In alcoholism, compared to the GG genotype, the OR 2.66 (0.93-7.57) and 8.4 (0.92-76.19) for the heterozygous GA and homozygous AA genotypes. Patients with mutant  homozygous AA, heterozygous GA genotypes showed 123.3+14.34 (mg/dl) and 76.92+24.09 Apo B level in CVD patients compared to wild type GG homozygous genotypes were 70.82+17.12. Conclusion: It was observed that Apo B gene polymorphism and smoking behaviour found to be associated with increased risk of CVD in Indian population.

Association Analysis between Genetic Polymorphisms of CYP4A11, Apolipoprotein B and E Genes and Essential Hypertension Susceptibility / 昆明医科大学学报

Objective To investigate the association between single nucleotide polymorphisms (SNPs) in CYP4A11 and ApoB、 ApoE genesandthe risk of essential hypertension. Methods By means of correlation analysis, this case-controlled study included a total of 350 essential hypertension patients admitted in the first Hospital of Xi'an from June 2012 to December 2016, and another 350 cases with matched ages and sexes enrolled for routine check-ups as the healthy control group. The genotypes of CYP4A11 and ApoB、 ApoE genes were determined by MassARRAY method. SPSS 21.0 software was used to determine the correlation between SNPs and the risk of primary hypertension.Results Comparing the allele frequencies of SNPs, we found rs1126742 (OR=1. 45, 95 % CI, 1.09-1.92,P=0.008)、 rs3890011 (OR=1.98, 95 % CI, 1.06-1.85, P=0.001) and rs9332978 (OR=1.54, 95%CI, 1.27-1.91,P=0.004) on CYP4A11 were significantly associated with an increased risk of essential hypertension; XbaⅠpolymorphism in ApoB gene was associated with essential hypertension risks (OR=1.55,95%CI, 1.15-2.55,P=0.001);ε4 in ApoE gene was also found associated with essential hypertension risks (OR=1.49, 95 % CI, 1.09-2.35, P=0.012), while ε2 andε3 not associated.Comparing the genotype frequencies of SNPs,we found the GG genotype of rs9332978, TC and CC genotype of rs1126742, CG and GG genotypes of rs3890011 were associated with increased risks of essential hypertension (P＜0.05) .The X -X- genotype of XbaⅠin ApoB gene were associated with increased risks of essential hypertension (OR=2.45, 95%CI, 1.25-3.25, P=0.035) . The E2/E4、E3/E4、E4/E4 genotype of ApoE were associated with increased risks of essential hypertension (P＜0.05).In the genetic model analysis, we found that the minor allele "A" of rs9332978 was associated with an increased risk of essential hypertension under dominant model (P＜0.05) . The minor allele "T" of rs1126742 was associated with increased risks essential hypertension under dominant and recessive models (P＜0.05) . Conclusion Gene polymorphisms of CYP4A11、ApoB and ApoE play an important role in the occurrence and development of essential hypertension.

Advances of anti-inflammation therapy targeting ApoB-100 against atherosclerosis / 上海交通大学学报（医学版）

Atherosclerosis is an inflammatory disease of arterial wall caused by many factors, which is the main pathological basis of many cardiovascular diseases. Currently, "inflammatory response" theory is widely accepted as pathogenesis of atherosclerosis. Abnormal increase of apolipoprotein ApoB-100, a composition of low density lipoprotein (LDL), which causes pathological inflammation, is a major factor leading to atherosclerosis. Therefore, inhibition of ApoB-100 induced pathological inflammatory response by immunotherapy is expected to delay the development of atherosclerosis. This review focused on the recent advances of ApoB-100 vaccine and other ApoB-100 inhibitors against atherosclerosis.

Complejos inmunes IgM-ApoB100 modificadas / Immune complexes IgM-modified ApoB100 / Complexos Imunes IgM-ApoB100 modificadas

La aterosclerosis es la patología vascular de mayor prevalencia, lo cual motiva numerosas investigaciones sobre su fisiopatogenia. Las lipoproteínas pueden ser modificadas por mecanismos de oxidación y acetilación entre otros, a nivel de sus componentes lipídicos como proteicos, tornándose aterogénicas. Las Apolipoproteínas B100 modificadas (ApoB100m), desempeñan un rol activo en el desarrollo de las lesiones ateroscleróticas conjuntamente con otros factores de riesgo. Éstas tienen la capacidad de producir respuesta inmune llevando a la producción de anticuerpos y la subsecuente formación de complejos inmunes. La importancia de los anticuerpos contra las ApoB100m en la aterogénesis todavía no está clara, existiendo datos contradictorios respecto a si su rol es protectivo o aterogénico. Se establecieron dos objetivos: Determinar los niveles de complejos inmunes circulantes IgM-ApoB100m por enzimoinmunoanálisis, en sujetos normales (sin riesgo aterogénico) y pacientes con alto riesgo y establecer su correlación con los factores de riesgo aterogénico ya establecidos, mediante un estudio observacional transversal. Se obtuvieron valores medios más elevados de IgM-ApoB100m en el grupo de sujetos normales. Los complejos inmunes IgM-ApoB100m correlacionan negativamente con los factores de riesgo aterogénicos clásicos (sexo masculino, avanzada edad, dislipemia, LDL-C aumentado y HDL-C disminuido).

Atherosclerosis is the most prevalent vascular disease, which motivates extensive research on its pathogenesis. Lipoproteins can be modified by acetylation and oxidation mechanisms, at the level of lipid components as protein, becoming atherogenic. Modified Apolipoprotein B100 (ApoB100m), play an active role in the development of atherosclerotic lesions in conjunction with other risk factors. These have the ability to produce immune response leading to antibody production and subsequent formation of immune complexes. The importance of antibodies against ApoB100m in atherogenesis is still unclear since, contradictory data exist on whether their role is protective or atherogenic. Two objectives were established: to determine the levels of circulating immune complexes IgM-ApoB100m by enzyme immunoassay, in normal subjects (without atherogenic risk) and high-risk patients and to establish its correlation with atherogenic risk factors established by a cross-sectional study. Higher mean values of IgM-ApoB100m were obtained in the group of normal subjects. Immune complexes IgM-ApoB100 negatively correlated with classic atherogenic risk factors (male, older, dyslipidemia, increased LDL-C and decreased HDL-C).

A aterosclerose é a doença vascular mais prevalente, o que motiva numerosas pesquisas sobre sua patogênese. As lipoproteínas podem ser modificadas por meio de mecanismos de oxidação e de acetilação entre outros, em nível de seus componentes lipídicos como proteicos, tornando-se aterogênicas. As apolipoproteínas B100 modificadas (ApoB100m), desempenham um papel ativo no desenvolvimento de lesões ateroscleróticas em conjunto com outros fatores de risco. Elas têm a capacidade de produzir resposta imune que conduz à produção de anticorpos e subsequente formação de complexos imunes. A importância de anticorpos contra a ApoB100m na aterogênese ainda não é clara, existindo dados contraditórios sobre se seu papel é de proteção ou aterogênico. Foram estabelecidos dois objetivos. Determinar os níveis de complexos imunes circulantes IgM-ApoB100m por enzimoimunoanálise em indivíduos normais (sem risco aterogênico) e pacientes de alto risco e, estabelecer sua correlação com os fatores de risco aterogênico já estabelecidos por um estudo Observacional Transversal. Foram obtidos valores médios mais elevados de IgM-ApoB100m no grupo de indivíduos normais. Os complexos imunes IgM-ApoB100 correlacionam negativamente com os fatores de risco aterogênicos clássicos (sexo masculino, idosos, dislipidemia, LDL-C aumentado e HDL-C diminuído).

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.

The influence of lipid metabolic markers on hip osteoarthritis / 中华风湿病学杂志

Objective To investigate the influence of lipid metabolic markers on hip osteoarthritis (OA) and the correlation with the pain of hip.Methods In this retrospectively cross sectional analysis,393 subjects fufilling the inclusive criteria were continuously included from June 2013 to September 2014.The presentation of hip X-ray of subjects were classified into OA group and non-OA group in terms of Kellgren-Lawrence grading scale,the subjects with Kellgren-Lawrence (K-L)≥2 was classified into OA group.The average of age in total was (62±9) years.There were 183 males and 210 females,the number of patients with OA was 182.There were 210 patients with hypertension and 118 patients with diabetes while the number of smoking patients was 74.The demographic information,risk factors,blood pressure,blood glucose,lipid metabolic markers were analyzed.Differences in proportions were compared using the Chi-square test.Difterences in continuous variables were tested for statistical significance using t test analysis.VAS score was used to evaluate the severity of hip pain.Independent risk factors were confirmed by using multiple logistic regression analysis.The correlation between the risk factors and severity of hip pain was analyzed by Spearman correlation analysis.Results Statistically significance existed in age (t=-4.849),sex (x2=8.946),BMI (t=-4.794),hypertension (x2=4.751),smoking (x2=7.062),metabolic syndrome (x2=34.406),apolipoprotein A1 (t=2.352),apolipoprotein B (t=-6.870),high density lipoprotein cholesterol (t=2.519),triglyceride (t=-4.652) and ApoB/ApoA1 ratio (t=-4.901) between OA group and non OA group.Age [OR =1.060(1.033,1.086)],metabolic syndrome [OR=3.682(2.284,5.938)] and ApoB/ApoA1 ratio [OR=5.743(2.393,13.785)] were the independent risk factors.The ApoB/ApoA1 ratio had positive correlation with the severity of hip pain(r=0.379).Conclusion ApoB/ApoA1 ratio is the independent risk factor of hip osteoarthritis,and has positive correlation with the severity of hip pain.The ApoB/ApoA1 ratio should be monitored in hip osteoarthritis patients in clinical work,to get the relief of pain and improve hip osteoarthritis.

Effects of berberine-evodiamine compatibility on expressions of intestinal ACAT2, ApoB48 and NPC1L1 in hypercholesterolemic rat / 中成药

AIM To investigate the effects of berberine-evodiamine compatibility on expressions of intestinal acyl-CoA:cholesterol acyltransferase 2 (ACAT2),apolipoprotein B48 (ApoB48),and Niemann-Pick C1 Like 1 (NPC1L1) proteins in hypercholesterolemic rats.METHODS Fifty SD rats were assigned to control and model groups.After establishing the hypercholesterolemic rat model by feeding high fat and high cholesterol food,forty SD rats were equally divided into model control group,atorvastatin group,berberine-evodiamine compatibility groups (89.2 mg/kg,178.4 mg/kg).After four weeks treatment,serum triglycerides (TG),total cholesterol (TC),low-density lipoprotein cholesterol (LDL-C),high density lipoprotein cholesterol (HDL-C) were detected.Then the contents of cholesterol and β-sitoesterol in serum were determined by GC.The expressions of ACAT2,ApoB48 and NPC1 L1 proteins in the small intestine were assayed with immunohistochemistry technology.RESULTS Serum TC,TG and liver TC were significantly decreased in 89.2 mg/kg and 178.4 mg/kg berberineevodiamine compatibility groups compared with those in the model control group (P ＜ 0.01).Serum LDL-C and liver TC were also significantly decreased in 89.2 mg/kg berberine-evodiamine compatibility group (P ＜ 0.05).GC analysis indicated that the amount of cholesterol level and β-sitoesterol in serum were decreased in 178.4 mg/kg berberine-evodiamine compatibility group (P ＜ 0.05) and 89.2 mg/kg berberine-evodiamine compatibility group (P ＜ 0.01).Immunohistochemistry analysis manifested that the average luminous density of ACAT2,ApoB48 and NPC1L1 proteins in two dosages of berberine-evodiamine compatibility group were descended markedly compared with those in the model control group (P ＜ 0.05 or P ＜ 0.01).CONCLUSION The mechanisms underlying the cholesterol metabolism activity of berberine-evodiamine compatibility are mediated most likely by down-regulating the expressions of intestinal ACAT2,ApoB48 and NPC1 L1 proteins in hypercholesterolemic rats.

Effects of berberine-evodiamine compatibility on expressions of intestinal ACAT2, ApoB48 and NPC1L1 in hypercholesterolemic rat / 中成药

AIM To investigate the effects of berberine-evodiamine compatibility on expressions of intestinal acyl-CoA:cholesterol acyltransferase 2 (ACAT2),apolipoprotein B48 (ApoB48),and Niemann-Pick C1 Like 1 (NPC1L1) proteins in hypercholesterolemic rats.METHODS Fifty SD rats were assigned to control and model groups.After establishing the hypercholesterolemic rat model by feeding high fat and high cholesterol food,forty SD rats were equally divided into model control group,atorvastatin group,berberine-evodiamine compatibility groups (89.2 mg/kg,178.4 mg/kg).After four weeks treatment,serum triglycerides (TG),total cholesterol (TC),low-density lipoprotein cholesterol (LDL-C),high density lipoprotein cholesterol (HDL-C) were detected.Then the contents of cholesterol and β-sitoesterol in serum were determined by GC.The expressions of ACAT2,ApoB48 and NPC1 L1 proteins in the small intestine were assayed with immunohistochemistry technology.RESULTS Serum TC,TG and liver TC were significantly decreased in 89.2 mg/kg and 178.4 mg/kg berberineevodiamine compatibility groups compared with those in the model control group (P ＜ 0.01).Serum LDL-C and liver TC were also significantly decreased in 89.2 mg/kg berberine-evodiamine compatibility group (P ＜ 0.05).GC analysis indicated that the amount of cholesterol level and β-sitoesterol in serum were decreased in 178.4 mg/kg berberine-evodiamine compatibility group (P ＜ 0.05) and 89.2 mg/kg berberine-evodiamine compatibility group (P ＜ 0.01).Immunohistochemistry analysis manifested that the average luminous density of ACAT2,ApoB48 and NPC1L1 proteins in two dosages of berberine-evodiamine compatibility group were descended markedly compared with those in the model control group (P ＜ 0.05 or P ＜ 0.01).CONCLUSION The mechanisms underlying the cholesterol metabolism activity of berberine-evodiamine compatibility are mediated most likely by down-regulating the expressions of intestinal ACAT2,ApoB48 and NPC1 L1 proteins in hypercholesterolemic rats.

Effects of APOA1 and APOB100 on Progression of Coronary Artery Lesion / 中山大学学报(医学科学版)

[Objective] The retrospective study was designed to analyze the dynamic relationship between the Apolipoprotein A 1,B100 and the progression of coronary artery lesion.[Methods] Patients who underwent the second coronary angiography or coronary 320-slice CTA at a minimum review interval of 6 months after their first examinations in the Third Affiliated Hospital of Sun Yat-sen University from 2010 to 2015 (n =245),were divided into non progress group (n =114) and progress group (n =131).We compared the differences of clinical and Biochemical data between two groups,and tried to find out the relationship by Logistic Regression analysis.[Results] The baseline levels of APOA1 (1.33 ± 0.29 vs 1.24 ± 0.25,P =0.015),APOA1/AOPB100(1.56 ± 0.65 vs 1.38 ± 0.44,P =0.014)in non progress group were higher than those in progress group.The baseline levels of APOB 100 were similar in both groups.The follow-up levels of APOA1 were higher than the baseline levels in both groups,the variation was significant in progress group (1.24 -± 0.25 vs 1.31 ± 0.28,P =0.006).The levels of APOA1 and APOA1/APOB100 were correlated with progression of coronary artery lesion negatively in single-variate logistic regression analysis.The level of APOA 1 (OR =0.245,P =0.005) was correlated with progression of coronary artery lesion negatively in multivariate logistic regression analysis.[Conclusions] APOA1 may has the effect of delaying the progression of coronary artery lesion,and may predict the progression of coronary artery lesion.

Association of ApoB/A-1 ratio with type 2 diabetes mellitus in Chinese Han ethnic population:A cross-sectional study / 中华内分泌代谢杂志

In this cross-sectional study, consecutive Chinese Han ethnic inpatients in the Division of Cardiology, the First Affiliated Hospital of Soochow University from January 1, 2010 to December 31, 2013 were included. According to the exclusion criteria, 9 587 patients [1 604 with type 2 diabetes mellitus (T2DM) and 7 983 without T2DM]were obtained for final analysis. Logistic regression model was used to analyze the association of ApoB/A-1 ratio with T2DM and the possible interactions between ApoB/A-1 ratio and other risk factors. The results showed that the distribution of ApoB/A-1 ratio was positively skewed in Chinese Han ethic population. The median of ApoB/A-1 ratio of female was lower than that of male (0.68 vs 0.73,P<0.01). In all groups, the proportion of T2DM was increased with the raised ApoB/A-1 ratio. By the stratification analyses of sex, age, coronary artery disease, and the use of statins, ApoB/A-1 ratio was still correlated with T2DM. There existed significant interactions between ApoB/A-1 ratio and the smoking status or creatinine in T2DM.

A study on the relationship between ApoB/ApoA1 and carotid intima -media thickness among obese children / 预防医学

Objective To explore the relationship between ApoB/ApoA1 ratio and the common carotid arterial intima -media thickness (CCA IMT)among obese children.Methods A total of 53 obese children in the Zhuji People's hospital outpatient were enrolled as obese group.Other 59 no -obese healthy children were recruited as control group.Serum fasting glUAose (FG),fasting insulin (FI),total cholesterol (TC),triglyceride (TG),high density lipoprotein cholesterol (HDL -C),low density lipoprotein cholesterol (LDL -C),lipoprotein A,apolipoprotein A1 (ApoA1 ), apolipoprotein B (ApoB),alanine aminotransferase (ALT),aspartate amino transferase (AST),and uric acid (UA) were measured in the clinical laboratory.Body mass index (BMI),waist to hipline (W/H)ratio,ApoB/ApoA1 ratio, insulin resistance by homeostasis model (HOMA -IR),and βcell function by homeostasis model (HOMA -β)were calculated.The common carotid arterial IMT of obese children was measured by B -mode ultrasound.All factors between two groups were compared by independent t test.The differences between the two groups were compared,and the correlation between CCA IMT and other factors in obesity group was analyzed by stepwise multiple regression model.Results In the obese group,lg(ALT),lg(AST),lg(UA),ln(10*TG),TC,LDL -C,ApoB,ApoB/ApoA1,lg(HOMA -β), and ln(10* HOMA -IR)were significantly higher than those in control group (P <0.05,respectively)while HDL -C and ApoA1 in obese group were lower than those in control group (P <0.01,respectively).Bivariate correlation analysis showed that CCA IMT was inversely correlated with ApoA1 and positively correlated with ApoB/ApoA1,lg(ALT),and lg (AST)(P <0.05,respectively).Analysis using multiple regression method showed that ApoB/ApoA1 was positively correlated with CCA IMT in these obese children (P <0.05 ).Conclusion In obese children,ApoB /ApoA1 was the independent determinant of CCA IMT,which may be a risk factor for atherosclerosis early in life.

ApoB/ApoA-I Ratio is a Potential Marker to Assess the Severity of Chronic Hepatitis B Virus Infection / 现代检验医学杂志

Objective To observe the change of the sera lipid profiles in patients with chronic hepatitis B Virus (HBV)infec-tion.Methods Sera from 254 patients suffered from liver disease were collected and divided into four groups according to the severity of the disease (71 of Cirrhosis;80,46,51 of Light,Moderate and Highly severity of the chronic HBV infection, respectively).Sera of 59 healthy patients were collected as control.The concentrations of their sera lipids (CHOL and TG), lipoprotein (HDL and LDL)and apolipoproteins (ApoA-I and ApoB)were determined and compared.Results Compared to the control group,the levels of the CHOL,TG,HDL,LDL,ApoA-I and ApoB were varied in degree in the chronic HBV in-fection group and the cirrhosis group.For the highly severity group and the cirrhosis group,statistics analysis showed de-creased and significantly different lipid and apolipoprotein results when compared to the control group.For the light and moderate severity group,when compared to the control group,levels of TG,HDL and ApoA-I were decreased with remarka-ble difference.The ApoB/ApoA-I ratio of the chronic HBV infection (Highly severity group)was 2.10±1.44,which was significantly higher than that of any other group (P<0.05).Conclusion The ApoB/ApoA-I ratio can be a potential marker for the evaluation of the severity of the chronic HBV infection.

-LDL/ApoB-100 en niños obesos resistentes a la insulina como herramienta clínica para valorar el riesgo cardiovascular / c-LDL/ApoB-100 in insulin resistance obese children as a clinical tool for assessing cardiovascular risk / c-LDL/Apo B-100 em crianças obesas insulino-resistentes como ferramenta clínica para avaliar o risco cardiovascular

La obesidad es la enfermedad nutricional más frecuente en niños y adolescentes en los países desarrollados. Se caracteriza por un estado proinfamatorio que supone una interrupción de las señales de traducción de la insulina con la consiguiente resistencia a la insulina. El objetivo del estudio fue valorar la presencia de factores de riesgo cardiovasculares y de partículas de c-LDL pequeñas y densas mediante el cálculo del índice c-LDL/ApoB-100 en una población infantil obesa insulinorresistente. Se incluyeron niños de ambos sexos con edades comprendidas entre 2 y 12 años que acudieron a las consultas de pediatría del Hospital Universitario Virgen Macarena. Se reclutó una cohorte de 200 niños correspondiente a un total de 97 niños y 103 niñas distribuidos en los siguientes grupos: Grupo 1: n=96 con obesidad (P97) y resistencia a la insulina (RI); y Grupo 2, n=104, con peso normal (P<80). Se calculó el per-centilo del IMC para cada edad y sexo así como se analizó el perfil lipídico y bioquímico. Ambos grupos contaron con el consentimiento informado previo a la extracción de la muestra por parte de los familiares. El cociente c-LDL/ApoB-100 alcanzó mayor significación estadística y área bajo la curva (AUC) que otros cocientes valorados, con una sensibilidad (S)=87 y especificidad (E)=0,585 para el valor de 1,3 y un AUC de 0,78 y p<0,001. Además, se obtuvo una correlación negativa entre el cociente c-LDL/ApoB-100 y el HOMA (p<0,05), el fbrinógeno (p<0,05) y us-PCR (p<0,05). El cociente c-LDL/ApoB-100 podría ser un parámetro determinante de la presencia de partículas pequeñas y densas con alta sensibilidad, significación estadística y valor predictivo positivo en una población infantil obesa e insulinorresistente como herramienta clínica para valorar el riesgo cardiovascular.

Obesity is the most common( nutritional disease in children and adolescents in developed countries. It is a proinfammatory disease that implies a break in the transduction signal of insulin with subsequent insulin resistance. The aim of the study was to assess the presence of particles of small and dense c-LDL by calculating the c-LDL/ApoB-100 index in an insulin resistant obese children population. Children of both sexes aged between 2 and 12 attending the pediatric outpatient clinics of Hospital Universitario Virgen Macarena were included. It recruited a cohort of 200 children, with a total of 103 girls and 97 boys distributed in the following groups: Group 1: n=96 obese (P97) and IR and n=104 normal weight, Group 2 (P<80). BMI percentile for age and sex as well as lipid and biochemical profle were calculated. Both groups had informed consent from relatives before the extraction. The c-LDL/ApoB-100 achieved greater statistical significance and area under the curve (AUC) than other ratios measured with sensibil-ity (S)=87 and specificity (E)=0.585 for the value of 1.3 with an AUC of 0.78 and p<0.001. Besides, a negative correlation between the c-LDL/Apo-B-100 and HOMA (p<0.05), fbrinogen (p<0.05) and us-PCR (p<0.05) ratios is obtained. The LDL/ApoB-100 ratio is a determining parameter for presence of small and dense LDL particles with high sensitivity, statistical significance and positive predictive value in an insulin resistant obese children population as a clinical tool to assess cardiovascular risk.

A obesidade é a doença nutricional mais comum em crianças e adolescentes nos países desenvolvidos. Caraceriza-se por um estado pró-infamatório que supõe uma interrupção dos sinais de tradução da insulina com a conseguinte resistência à insulina. O objetivo do estudo foi avaliar a presença de fatores de risco cardiovasculares e de partículas de c-LDL pequenas e densas através do cálculodo índice c-LDL/ Apo B-100 numa população infantil resistente à insulina. Foram incluídas crianças de ambos os sexos com idade entre 2 e 12 anos, que foram às consultas de pediatria do Hospital Universitário Virgem Macarena. Foi recrutado um grupo de 200 crianças, correspondente a um total de 97 meninos e 103 meninas distribuídos nos seguintes grupos: Grupo 1: n=96 obesidade (P97) e resistência à insulina (RI) e n=104 Grupo 2 de peso normal (P<80). Calculou-se o percentil do IMC para cada idade e sexo, bem como o perfil lipídico e bioquímico. Ambos os grupos tinham o consentimento informado antes da ex-tração da amostra por parte da família. O quociente de c-LDL/ApoB-100 atinge significação estatística maior e área sob a curva que outros quocientes avaliados com uma sensibilidade (S)=87 e especificida-de (E)=0,585 para o valor de 1,3, e uma AUC de 0,78 e p<0,001. Além disso, foi obtida uma correla-ção negativa entre o quociente c-LDL/Apo-B-100 e o HOMA (p<0,05), o fbrinogênio (p<0,05) e us-PCR (p<0,05). O quociente c-LDL/ApoB-100 poderia ser um parâmetro de determinação da presença de partículas pequenas e densas com alta sensibilidade, significação estatística e valor preditivo positivo numa população infantil obesa e insulino-resistente como ferramenta clínica para avaliar o risco cardiovascular.

Correlation between the Xba I polymorphism of apoB gene and serum lipid profiles in Li ethnic group

OBJECTIVE@#To study correlation between the Xba I polymorphism of apoB gene and plasma lipid profiles in Li ethnic group.@*METHODS@#Total 151 cases of healthy Li people were recruited randomly by cluster sampling and 200 Han people were recruited as control; blood was drawn to analyze Xba I polymorphism distribution of apoB gene and serum lipid levels.@*RESULTS@#There were lower serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels in serum of Li people; while, high density lipoprotein cholesterol (HDL-C), X-/X+ genotype and X+ allele frequencies exhibited higher levels than Han people. Interestingly, HDL-C level was reduced, while LDL-C level was enhanced in subjects carrying heterozygous (X-/X+) genotype compared to homozygous (X-/X-) genotype. Additionally, there were no difference in serum level of triglyceride, TC, apoprotein A (apo A) and apoprotein B (apo B) between Li and Han people, the same results were showed between X-/X+ and X-/X- genotype carriers.@*CONCLUSIONS@#Xba I polymorphism of apoB gene is correlated to the profiles of serum lipid level, X-/X+ genotype carriers are phenotyped with higher LDL-C level and lower level of HDL-C in Li ethnic group.

Marcadores de respuesta inflamatoria y riesgo coronario en pacientes con artritis reumatoide / Markers of inflammatory response and coronary risk in patients with rheumatoid arthritis

Objetivo: evaluar la asociación entre los niveles séricos de Proteína C Reactiva e índices Apoproteína B/Apoproteína A1, Apoproteína B/LDL colesterol, LDL/HDL colesterol, índice aterogénico, lipoproteína (a) y componentes C3 y C4 del complemento sérico; así como la capacidad predictiva de la proteína C Reactiva, C3 y C4 complemento sobre los parámetros del lipidograma mencionados, se realizó un estudio transversal en pacientes portadores de Artritis Reumatoide y controles sanos de la provincia Matanzas. Métodos: las determinaciones de los parámetros individuales fueron realizadas por método inmunoturbidimétrico y enzimocolorimétrico. El Software estadístico SPSS, versión 18,0 fue empleado para el procesamiento de los resultados. Resultados: la correlación de Spearman detectó asociación de la proteína C Reactiva con los índices ApoB/LDL colesterol y LDL/HDL colesterol exclusivamente en los pacientes, Rho de Spearman= 0,439 (p=0,002); -0,300 (p=0,043), respectivamente; mientras manifestó asociación de esta con el C4 complemento en ambos grupos, Rho de Spearman= 0,355 (p=0,015); 0,376 (p=0,000), pacientes y controles, respectivamente. La proteína C reactiva predijo el índice ApoB/LDL colesterol mediante el análisis de regresión lineal en los pacientes: R²=0,192 F=10,488 (p=0,002), en tanto las proteínas del complemento C3 y C4 estimaron significativamente el nivel de lipoproteína(a); R²=0,170 F=4,396 (p=0,018). Los resultados apoyan la hipótesis del vínculo entre respuesta inflamatoria y predominio de Lipoproteínas de baja densidad más proaterogénicas; así como la posible estimación de marcadores del riesgo coronario relacionados con el metabolismo lipoproteico a partir de los niveles séricos de Proteína C Reactiva, C3 y C4 complemento en pacientes con Artritis Reumatoide...

Objective: evaluate the association between serum levels of C-reactive protein and the indices apoprotein B/apoprotein A1, apoprotein B/LDL cholesterol, LDL/HDL cholesterol, atherogenic index, lipoprotein (a) and serum complement components C3 and C4, as well as the prediction capacity of C-reactive protein, C3 and C4 complement with respect to the above mentioned lipidogram parameters. A cross-sectional study was conducted of patients with rheumatoid arthritis and healthy controls from the province of Matanzas. Methods: individual parameters were determined by immunoturbidimetry and enzymatic colorimetry. Results were processed with the statistical software SPSS version 18.0. Results: spearman rank correlation spotted an association of C-reactive protein with indices ApoB/LDL cholesterol and LDL/HDL cholesterol exclusively in patients, Spearman's Rho = 0.439 (p=0.002); -0.300 (p=0.043); -0.300 (p=0.043), respectively; and an association of C-reactive protein with C4 complement in both groups, Spearman's Rho = 0.355 (p=0.015); 0.376 (p=0.000), patients and controls, respectively. C-reactive protein predicted the ApoB/LDL cholesterol index by linear regression analysis in patients: R²=0.192 F=10.488 (p=0.002), whereas C3 and C4 complement proteins significantly estimated the level of lipoprotein (a): R²=0.170 F=4.396 (p=0.018). Results support the hypothesis about the link between inflammatory response and the predominance of more proatherogenic low density lipoproteins, as well as the potential estimation of coronary risk markers related to lipoprotein metabolism based on serum levels of C-reactive protein, C3 and C4 complement in patients with rheumatoid arthritis...

Association of ApoB/ApoA-1 Ratio with Insulin Resistance in Patients with Non-alcoholic Fatty Liver Disease / 昆明医科大学学报

Objective This study aims to investigate the association of apoB/apoA-1 ratio with insulin resistance (IR) in patients with non-alcoholic fatty liver disease (NAFLD) . Methods A total of 224 patients with NAFLD and 166 healthy subjects were enrolled as NAFLD group and control group. Weight, height and blood pressure were recorded. Serum levels of fasting blood glucose (FPG), insulin (Fins), lipids, glycated hemoglobin (HbA1c) were measured. Homeostasis model assessment-insulin resistance (HOMA-IR) indices were calculated. Results Compared with control group, NAFLD group had higher apoB/apoA-1 ratio (0.76 ± 0.28 vs 0.61 ± 0.26) and HOMA-IR (2.43 ± 1.68 vs 1.86 ± 1.61) . Spearman correlation analysis showed that in NAFLD group, HOMA-IR positively correlated with age, body mass index (BMI), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), apoB/apoA-1 ratio (r =0.34, P < 0. 05) and HbA1c, and negatively correlated with high-density lipoprotein cholesterol (HDL-c) . Multiple linear regression analysis revealed that apoB/apoA-1 ratio was still associated with HOMA-IR in NAFLD group after adjustment for age and BMI. Conclusion The apoB/apoA-1 ratio is closely associated with IR in patients with NAFLD. ApoB/apoA-1 ratio may play a role in the development of IR in NAFLD.