Complex genetic relationships between neurodegenerative disorders and neuropsychiatric symptoms have been shown, suggesting shared pathogenic mechanisms and emphasizing the potential for developing common therapeutic ...Complex genetic relationships between neurodegenerative disorders and neuropsychiatric symptoms have been shown, suggesting shared pathogenic mechanisms and emphasizing the potential for developing common therapeutic targets. Apolipoprotein E(APOE) genotypes and their corresponding protein(Apo E) isoforms may influence the biophysical properties of the cell membrane lipid bilayer. However, the role of APOE in central nervous system pathophysiology extended beyond its lipid transport function. In the present review article, we analyzed the links existing between APOE genotypes and the neurobiology of neuropsychiatric symptoms in neurodegenerative and vascular diseases. APOE genotypes(APOE ε2, APOE ε3, and APOE ε4) were implicated in common mechanisms underlying a wide spectrum of neurodegenerative diseases, including sporadic Alzheimer's disease, synucleinopathies such as Parkinson's disease and Lewy body disease, stroke, and traumatic brain injury. These shared pathways often involved neuroinflammation, abnormal protein accumulation, or responses to acute detrimental events. Across these conditions, APOE variants are believed to contribute to the modulation of inflammatory responses, the regulation of amyloid and tau pathology, as well as the clearance of proteins such as α-synuclein. The bidirectional interactions among Apo E, amyloid and mitochondrial metabolism, immunomodulatory effects, neuronal repair, and remodeling underscored the complexity of Apo E's role in neuropsychiatric symptoms associated with these conditions since from early phases of cognitive impairment such as mild cognitive impairment and mild behavioral impairment. Besides Apo E-specific isoforms' link to increased neuropsychiatric symptoms in Alzheimer's disease(depression, psychosis, aberrant motor behaviors, and anxiety, not apathy), the APOE ε4 genotype was also considered a significant genetic risk factor for Lewy body disease and its worse cognitive outcomes. Conversely, the APOE ε2 variant has been observed not to exert a protective effect equally in all neurodegenerative diseases. Specifically, in Lewy body disease, this variant may delay disease onset, paralleling its protective role in Alzheimer's disease, although its role in frontotemporal dementia is uncertain. The APOE ε4 genotype has been associated with adverse cognitive outcomes across other various neurodegenerative conditions. In Parkinson's disease, the APOE ε4 allele significantly impacted cognitive performance, increasing the risk of developing dementia, even in cases of pure synucleinopathies with minimal co-pathology from Alzheimer's disease. Similarly, in traumatic brain injury, recovery rates varied, with APOE ε4 carriers demonstrating a greater risk of poor long-term cognitive outcomes and elevated levels of neuropsychiatric symptoms. Furthermore, APOE ε4 influenced the age of onset and severity of stroke, as well as the likelihood of developing stroke-associated dementia, potentially due to its role in compromising endothelial integrity and promoting blood–brain barrier dysfunction.展开更多
Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primar...Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment.Metabolic abnormalities are commonly observed in patients with Alzheimer's disease.The liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's disease.Notably,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease.In this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism.Furthermore,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.展开更多
Background:Chronic obstructive pulmonary disease(COPD)is a prevalent respiratory ailment that has risen to become the foremost cause of mortality globally,and statins are a widely used class of lipid-modifying drugs.D...Background:Chronic obstructive pulmonary disease(COPD)is a prevalent respiratory ailment that has risen to become the foremost cause of mortality globally,and statins are a widely used class of lipid-modifying drugs.Data from some observational studies suggest an association between statins use and COPD.Objectives:The main objective of this study was to investigate whether lipids and apolipoproteins are bidirectionally causally associated with COPD at the genetic level using a Mendelian randomization(MR)design,and to determine the potential role of circulating inflammatory proteins as mediators in this association.Methods:The publicly available Genome-Wide Association Study(GWAS)database was utilised for the purposes of the analysis.The data on high-density lipoprotein(HDL-C),low-density lipoprotein(LDL-C),triglycerides(TG),apolipoprotein A-1(ApoA1),and apolipoprotein B(ApoB)were obtained from the UK BioBank,while the COPD dataset was obtained from the FinnGen BioBank R11(number of cases:21,617,number of controls:372,627).Furthermore,data were gathered on genetic variants linked to inflammatory processes,encompassing 91 circulating inflammatory proteins(n=14,823 individuals).A two-sample MR study was conducted using these data to assess the association between HDL-C,LDL-C,TG,ApoA1,and ApoB with the risk of COPD.Furthermore,in order to investigate the potential mediating influence of inflammatory factor alterations between lipids and COPD,a two-step Mendelian randomization(MR)mediation analysis was conducted.Results:The forward MR methods identified two lipids that were found to have a causal relationship with the development of COPD.An elevated level of LDL-C and ApoB was found to be associated with a diminished risk of COPD.Furthermore,the researchers identified circulating inflammatory factors that were determined to be the causal agents in the development of COPD.Mediation analysis indicated that the inflammatory protein S100-A12 may act as a mediator between the LDL-C and COPD pathways.Conclusion:The present MR study provides genetic evidence for a causal relationship between lipids and apolipoproteins and COPD,as well as identifying the inflammatory protein S100-A12 as a potential mediator of the COPD association.The findings offer valuable insights into the mechanistic studies of statins for COPD and potential targets for disease intervention and treatment.展开更多
BACKGROUND Apolipoprotein E epsilon 4(APOE4)is recognized as a genetic risk factor for cognitive decline and neurodegeneration in both type 2 diabetes mellitus(T2DM)and Alzheimer’s disease,while glycated hemoglobin(H...BACKGROUND Apolipoprotein E epsilon 4(APOE4)is recognized as a genetic risk factor for cognitive decline and neurodegeneration in both type 2 diabetes mellitus(T2DM)and Alzheimer’s disease,while glycated hemoglobin(HbA1c)reflects persistent hyperglycemia and serves as a key indicator of long-term glycemic control in T2DM.Although both factors have been individually linked to neurobehavioral deficits,it remains uncertain whether HbA1c contributes to APOE4-related cognitive and olfactory impairment in individuals with T2DM.AIM To investigate the role of HbA1c in APOE4-associated cognitive and olfactory dysfunction in patients with T2DM.METHODS Of 636 T2DM patients were recruited from five medical centers in Wuhan,Hubei Province,China.APOE genotyping was evaluated by polymerase chain reaction using Gerard’s method.Cognitive and olfactory functions were assessed by mini-mental state examination and Connecticut chemosensory clinical research center test,respectively.Regression analysis was employed to assess the independent and interactive effects of HbA1c on APOE4-associated cognitive and olfactory function.RESULTS APOE4 was associated with increased risks of cognitive impairment[odds ratios(OR)=1.815,P=0.021]and olfactory dysfunction(OR=2.588,P<0.001).Higher HbA1c levels were also related to worse cognitive(OR=1.189,P<0.001)and olfactory performance(OR=1.149,P=0.011).HbA1c exerted a moderating effect,yet not a mediating effect,between APOE4 and its impacts on cognition and olfaction.Specifically,a higher level of HbA1c exacerbated the damaging effect of APOE4,as shown by significant interaction effects on both cognitive impairment(OR=2.687,P<0.001)and olfactory dysfunction(OR=1.440,P=0.027).CONCLUSION Elevated HbA1c levels are associated with increased risks of cognitive and olfactory impairments in patients with T2DM and may exacerbate the detrimental effects of APOE4.These findings underscore the need for early preventive strategies targeting individuals with both poor glycemic control and APOE4 carriage to mitigate neurodegenerative risk.展开更多
BACKGROUND Young-onset type 2 diabetes mellitus(T2DM)is associated with adverse health outcomes and increased mortality.Vitamin D(VitD)deficiency is likewise linked to various adverse health outcomes and is significan...BACKGROUND Young-onset type 2 diabetes mellitus(T2DM)is associated with adverse health outcomes and increased mortality.Vitamin D(VitD)deficiency is likewise linked to various adverse health outcomes and is significantly associated with lipid metabolism in patients with T2DM.However,little is known regarding the me-chanisms of interaction between VitD and apolipoprotein A1(apoA1)in young-onset T2DM.AIM To evaluate the relationship between VitD and apoA1 levels in patients with young-onset T2DM.METHODS This cross-sectional study was conducted at Zhejiang Provincial People’s Hospital between January 2019 and December 2023.A total of 642 patients with T2DM who aged 18-40 years were included and matched with 642 individuals without diabetes(controls)based on age and sex.No specific intervention was applied,and data were collected from medical records and laboratory tests.The re-lationship between VitD and apoA1 levels was examined using Spearman’s correlation and logistic regression models.RESULTS We found that VitD levels were significantly lower in patients with T2DM compared to controls(15.9 ng/mL vs 17.4 ng/mL,P<0.001),with a notable positive correlation between VitD deficiency and reduced apoA1 levels.Multifactor logistic regression analysis identified that severe VitD deficiency was an independent risk factor for apoA1 in young-onset T2DM patients(odds ratio=3.43,95%confidence interval:1.16-10.20,β=1.23,P=0.026).CONCLUSION Our findings reveal an association between VitD and apoA1 in young-onset T2DM,suggesting that VitD may play a crucial role in metabolic regulation and cardiovascular risk management.展开更多
BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a cancer with a poor prognosis,characterized by distinct geographical distribution and family clustering.AIM To investigate if ethnic differences(Han vs Kazakh)cau...BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a cancer with a poor prognosis,characterized by distinct geographical distribution and family clustering.AIM To investigate if ethnic differences(Han vs Kazakh)cause molecular variations in ESCC patients via genomic sequencing 299 samples.METHODS Here,we sequenced samples from 299 ESCC patients collected from Henan Key Laboratory for Esophageal Cancer Research and National Key Laboratory of Metabolic Dysregulation and Esophageal Cancer Prevention and Treatment,The First Affiliated Hospital of Zhengzhou University,including Han and Kazakh ethnic groups,and performed a genomic comparative analysis of these two ethnic cohorts.RESULTS ESCC patients of Kazakh ethnicity present with a later age of onset compared to Han.Kazakh patients exhibit a slightly higher tumor mutation burden compared to their Han counterparts.Three genes GIGYF1,CACNA1D,and ACOT11 exhibited mutation frequencies threefold higher in Kazakh patients than in Han.This enrichment may be associated with Kazakhs’adaptation to cold climates and consumption of high-calorie diets.Among Han patients,the apolipoprotein B messenger RNA-editing enzyme catalytic polypeptide(APOBEC)-associated single base substitutions(SBS)13 mutational signature is more prevalent,whereas SBS6,indicative of DNA mismatch repair deficiency,is more common in Kazakh patients.Additionally,Han Chinese patients with APOBEC-enriched tumors exhibit a significantly higher mutation load than those without.Moreover,patients lacking the APOBEC signature demonstrate superior survival probability compared to the APOBEC-enriched group.CONCLUSION Living environment and diet are major factors in the development of ESCC.Genomic difference may provide guidance for the formulation of clinical treatment plans for ESCC from different ethnics regions.展开更多
Objective: To study the effects of Apolipoprotein E (ApoE) polymorphism onserum levels of lipids, lipoproteins and apolipoproteins. Methods: Fragments of ApoE gene forthex-on containing codon 112 and 158 polymorphic l...Objective: To study the effects of Apolipoprotein E (ApoE) polymorphism onserum levels of lipids, lipoproteins and apolipoproteins. Methods: Fragments of ApoE gene forthex-on containing codon 112 and 158 polymorphic locus were amplified by PCR, and then digested untilCfo I endonuclease. Genotypes and alleles frequencies of 168 healthy persons in Jiangsu area werecalculated. The effects of ApoE genotypes and alleles on serum lipids, lipoproteins andapolipoproteins variation were analyzed. Results: The effects of ApoE alleles on total cholesterol(TC), law density lipoprotein-cholesterol (LDL-C), ApoB was: along a decreasing gradientε_4>ε_3>ε_2. The effect of ε_4 allele was to increase serum levels of TC, LDL-C and ApoB, andthe ε_2 allele had an effect opposite to that of ε_4 allele. Conclusion: ApoE polymorphism is anindependent genetic factor on individual serum levels of lipids and apolipoproteins.展开更多
研究背景:研究证实阿司匹林对控制慢性血管疾病进展有显著效果,抗血小板药物应运而生。目前状况:抗血小板药物成为防治老年慢性疾病(chronic diseases of old age)不能或缺的常规性辅助治疗方案,阿司匹林、氯吡格雷、华法林、地奥斯明...研究背景:研究证实阿司匹林对控制慢性血管疾病进展有显著效果,抗血小板药物应运而生。目前状况:抗血小板药物成为防治老年慢性疾病(chronic diseases of old age)不能或缺的常规性辅助治疗方案,阿司匹林、氯吡格雷、华法林、地奥斯明、利伐沙班等临床应用逐年增多,但效果参差不齐;同时,发生抗血小板药物抵抗或出血风险等不良反应的情况逐年增多,不但影响疗效,有些还威胁患者的生命,长期应用抗血小板药物的安全性问题可见一斑,安全有效的抗血小板方案备受关注。研究方法:对使用抗血小板药物的慢性血管疾病患者,观察其临床表现和治疗反应,检测其CYP2C19、APOE基因突变情况,用对照研究的方法探讨CYP2C19、APOE基因突变,慢性血管疾病临床表征及其与抗血小板药物反应的关系。结果和结论:CYP2C19和APOE基因突变在慢性血管疾病中可能有明确的临床特征,精准地掌控CYP2C19和APOE基因突变及其与临床药物精准靶点的关系,对慢性血管疾病的精准诊断和精准治疗都有现实意义。展开更多
BACKGROUND:Hypertriglyceridemia is an unusual cause of acute pancreatitis and sometimes considered to be an epiphenomenon.This study aimed to investigate the clinical and analytical features and the APOE genotypes in ...BACKGROUND:Hypertriglyceridemia is an unusual cause of acute pancreatitis and sometimes considered to be an epiphenomenon.This study aimed to investigate the clinical and analytical features and the APOE genotypes in patients with acute pancreatitis and severe hypertriglyceridemia.METHODS:We undertook a one-year,prospective study of patients with acute pancreatitis whose first laboratory analysis on admission to the emergency department included measurement of serum triglycerides.The APOE genotype was determined and the patients answered an established questionnaire within the first 24 hours concerning their alcohol consumption,the presence of co-morbidities and any medications being taken.The patients’ progression,etiological diagnosis,hospital stay and clinical and radiological severity were all recorded.RESULTS:Hypertriglyceridemia was responsible for 7 of 133 cases of pancreatitis (5%);the remaining cases were of biliary (53%),idiopathic (26%),alcoholic (11%) or other (5%) origin.Compared with these remaining cases,the patients with hypertriglyceridemia were significantly younger,had more relapses,and more often had diabetes mellitus.They usually consumed alcohol or consumed it excessively on the days before admission.Also,the ε4 allele of the APOE gene was more common in this group (P<0.05).CONCLUSION:One of 20 episodes of acute pancreatitis is caused by hypertriglyceridemia and it is linked to genetic (ε4 allele) and comorbid factors such as diabetes and,especially,alcohol consumption.展开更多
AIM： To identify a multi serum protein pattern as well as single protein markers using surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry （SELDI-TOF-MS） for detection and differentiation ...AIM： To identify a multi serum protein pattern as well as single protein markers using surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry （SELDI-TOF-MS） for detection and differentiation of liver fibrosis （F1-F2）, liver cirrhosis （F4） and hepatocellular carcinoma （HCC） in patients with chronic hepatitis C virus （HCV）. METHODS： Serum samples of 39 patients with F1/F2 fibrosis, 44 patients with F4 fibrosis, 34 patients with HCC were applied to CM10 arrays and analyzed using the SELDI-TOF ProteinChip System （PBS-Ⅱc; Ciphergen Biosystems） after anion-exchange fractionation. All patients had chronic hepatitis C and histologically confirmed fibrosis stage/HCC. Data were analyzed for protein patterns by multivariate statistical techniques and artificial neural networks. RESULTS： A 4 peptide/protein multimarker panel （7486, 12843, 44293 and 53598 Da） correctly identified HCCs with a sensitivity of 100% and specificity of 85% in a two way-comparison of HCV-cirrhosis versus HCV-HCC training samples （AUROC 0.943）. Sensitivity and specificity for identification of HCC were 68% and 80% for random test samples. Cirrhotic patients could be discriminated against patients with F1 or F2 fibrosis using a 5 peptide/protein multimarker pattern （2873, 6646, 7775, 10525 and 67867 Da） with a specificity of 100% and a sensitivity of 85% in training samples （AUROC 0.976） and a sensitivity and specificity of 80% and 67% for random test samples. Combination of the biomarker classifiers with APR/score and alfa-fetopotein （AFP） improved the diagnostic performance. The 6646 Da marker protein for liver fibrosis was identified as apolipoprotein C-I. CONCLUSION： SELDI-TOF-MS technology combined with protein pattern analysis seems a valuable approach for the identification of liver cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis C. Host probably a combination of different serum markers will help to identify liver cirrhosis and early-stage hepatocellular carcinomas in the future.展开更多
AIM: To determine the possible association of the ApoB100 (Xba Ⅰ ), ApoE (Hha Ⅰ ) and CYP7A1 (Bsa Ⅰ ) gene polymorphisms, with the development of cholesterol gallstone disease (GD) in a Mexican population. METHODS:...AIM: To determine the possible association of the ApoB100 (Xba Ⅰ ), ApoE (Hha Ⅰ ) and CYP7A1 (Bsa Ⅰ ) gene polymorphisms, with the development of cholesterol gallstone disease (GD) in a Mexican population. METHODS: The polymorphisms were analyzed by polymerase chain reaction followed by restriction fragment length polymorphism, in two groups matched by ethnicity, age and sex: patients with GD (n = 101) and stone-free control subjects (n = 101). RESULTS: Allelic frequencies in patients and controls were: 34.16% vs 41.58% (P = 0.124) for X+of ApoB-100; 4.46% vs 5.94% (P = 0.501) for E2, 85.64% vs 78.22% (P = 0.052) for E3, 9.90% vs 15.84% (P = 0.075) for E4 of ApoE; and 25.74% vs 27.72% (P = 0.653) for C of CYP7A1. Differences in genotypic frequencies between the studied groups were not significant (P < 0.05). CONCLUSION: These results demonstrated that no association exists between the studied polymorphisms and cholelithiasis in this high prevalent population.展开更多
AIM:To prospectively investigate the association between the XbaⅠpolymorphisms of apolipoprotein B(APOB)gene and gallstone formation following gastrectomy.METHODS:The study was conducted between January 2005 and Dece...AIM:To prospectively investigate the association between the XbaⅠpolymorphisms of apolipoprotein B(APOB)gene and gallstone formation following gastrectomy.METHODS:The study was conducted between January 2005 and December 2006.A total of 186 gastric cancer patients who had undergone radical gastrectomy were grouped according to XbaⅠpolymorphisms of APOB gene(X+X-group,n=24 and X-X-group,n=162)and compared.The XbaⅠpolymorphisms of APOB gene were detected by polymerase chain reaction-restriction fragment length polymorphism(PCRRFLP).RESULTS:The incidence of gallstone was significantly higher in the X+X-group than in the X-X-group[54.2%vs 9.3%,RR=5.85(2.23-15.32),P<0.001].The serum levels of total cholesterol(TC)and low-density lipoprotein(LDL)were higher in the X+X-than in the X-X-group(4.02±1.12 vs 3.48±0.88,P=0.004 before surgery and 3.88±1.09 vs 3.40±0.86,P=0.008 after surgery).LDL was 2.21±0.96 vs 1.89±0.84(P=0.042)before surgery and 2.09±0.95 vs 1.72±0.85(P=0.029)after surgery in the two groups.No relationship was found between XbaⅠpolymorphisms and gallbladder motility.CONCLUSION:In Chinese patients after radical gastrectomy,X+allele of APOB gene is another risk factor for the development of gallstone besides the gallbladder motility disorder after surgery.展开更多
Objective To examine the relationship between apolipoprotein E (Apo E) gene polymorphism and risk of coronary artery disease (CAD), analyzing association of polymorphism with classical risk factors. Methods A total of...Objective To examine the relationship between apolipoprotein E (Apo E) gene polymorphism and risk of coronary artery disease (CAD), analyzing association of polymorphism with classical risk factors. Methods A total of 124 patients (including 84 Han population and 40 Uygur population) with angiographically verified CAD or myocardial infarction were prospectively evaluated. Data referring to hypertension, diabetes, and tobacco consump-tion were recorded. The levels of total cholesterol (TC), high density lipoprotein (HDL) cholesterol, Apo A1 and B, and triglycerides (TG) were determined. DNA was obtained from 124 patients and 70 controls. In order to determine Apo E genotypes, DNA was PCR amplified and digested with HhaI. The genetic polymorphism of Apo E is due to three common alleles, epsilon(ε) 2, ε3, ε4, at a single autosomal gene locus. These alleles determine the six phenotypes E2/2, E3/3, E4/4, E4/2, E4/3, and E3/2. Results In Uygur population, the frequency of the ε2, ε3, and ε4 was 0.155, 0.648, and 0.197 respectively. In Han po-pulation, the frequency of the ε2, ε3, and ε4 was 0.081, 0.772, and 0.146 respectively. In the patient group, the frequency of the ε2, ε3, and ε4was 0.060, 0.758, and 0.182 respectively. In the control group, the frequency of the ε2, ε3, and ε4 was 0.193, 0.671, and 0.136 respectively. ε2 frequency of Uygur’ patients and controls was 0.050 and 0.290 respectively. Serum low density lipoprotein (LDL) cholesterol, TC, and TG values tended to decrease from the Apo E-4 phenotypes to Apo E-2 phenotypes. When deletion polymorphism of ε2 was compared with the common risk factors for CAD, its risk ratio (RR) is 4.38. Conclusions These studies confirm and find that Apo E phenotype distribution in Uygur population differs significantly from that in Han population in Xinjiang. CAD patients have significantly lower ε2 allele and slightly higher ε3 or ε4 allele frequency than controls, especially in Uygur population. It shows protective effects of ε2 on CAD.展开更多
Hepatitis C virus(HCV) is a hepatotrophic virus and a major cause of chronic liver disease,including hepatocellular carcinoma,worldwide. The life cycle of HCV is closely associated with the metabolism of lipids and li...Hepatitis C virus(HCV) is a hepatotrophic virus and a major cause of chronic liver disease,including hepatocellular carcinoma,worldwide. The life cycle of HCV is closely associated with the metabolism of lipids and lipoproteins. The main function of lipoproteins is transporting lipids throughout the body. Triglycerides,free cholesterol,cholesteryl esters,and phospholipids are the major components of the transported lipids. The pathway of HCV assembly and secretion is closely linked to lipoprotein production and secretion,and the infectivity of HCV particles largely depends on the interaction of lipoproteins. Moreover,HCV entry into hepatocytes is strongly influenced by lipoproteins. The key lipoprotein molecules mediating these interactions are apolipoproteins. Apolipoproteins are amphipathic proteins on the surface of a lipoprotein particle,which help stabilize lipoprotein structure. They perform a key role in lipoprotein metabolism by serving as receptor ligands,enzyme co-factors,and lipid transport carriers. Understanding the association between the life cycle of HCV and lipoprotein metabolism is important because each step of the life cycle of HCV that is associated with lipoprotein metabolism is a potential target for anti-HCV therapy. In this article,we first concisely review the nature of lipoprotein and its metabolism to better understand the complicated interaction of HCV with lipoprotein. Then,we review the outline of the processes of HCV assembly,secretion,and entry into hepatocytes,focusing on the association with lipoproteins. Finally,we discuss the clinical aspects of disturbed lipid/lipoprotein metabolism and the significance of dyslipoproteinemia in chronic HCV infection with regard to abnormal apolipoproteins.展开更多
AIM: To evaluate the tissular expression of Androgen (A), Estrogen (E) and Progesterone (Pg) receptors, and Apolipoprotein D (ApoD), in liver tumors from resected hepatocellular carcinoma (HCC) cases in order to asses...AIM: To evaluate the tissular expression of Androgen (A), Estrogen (E) and Progesterone (Pg) receptors, and Apolipoprotein D (ApoD), in liver tumors from resected hepatocellular carcinoma (HCC) cases in order to assess their possible relationship to prognosis. METHODS: We performed an immunohistochemical study using tissue microarrays (containing more than 260 cancer specimens, from 31 HCC patients and controls) to determine the presence of specif ic antibodies against AR, ER, PgR and ApoD, correlating their findings with several clinico-pathological and biological variables. The staining results were categorized using a semi-quantitive score based on their intensity, and the percentage of immunostained cells was measured. RESULTS: A total of 21 liver tumors (67.7%) were positive for AR; 16 (51.6%) for ER; 26 (83.9%) for PgR and 12 (38.7%) stained for ApoD. We have found a wide variability in the immunostaining score values for each protein, with a median (range) of 11.5 (11.5-229.5) for AR; 11.1 (8.5-65) for ER; 14.2 (4-61) for PgR; and 37.7 (13.8-81.1) for ApoD. A history of heavy ethanol consumption, correlated positively with AR and PgR and negatively with ER status. HCV chronic infection also correlated positively with AR and PgR status. However, the presence of ApoD immunostaining did not correlate with any of these variables. Tumors with a positive immuno-staining for PgR showed a better prognosis. CONCLUSION: Our results indicate a moderate clinical value of the steroid receptor status in HCC, emphasizing the need to perform further studies in order to evaluate the possible role of new hormonal-based therapies.展开更多
Recent reports have shown that apolipoprotein E （APOE） polymorphisms are involved in neurodegenerative disease. However, it is unclear whether APOE affects post-stroke depression. Accordingly, we hypothesized that A...Recent reports have shown that apolipoprotein E （APOE） polymorphisms are involved in neurodegenerative disease. However, it is unclear whether APOE affects post-stroke depression. Accordingly, we hypothesized that APOE polymorphisms modify the risk of post-stroke depression. Here, we performed a hospital-based case-control study （including 76 cerebral infarction cases with post-stroke depression, 88 cerebral infarction cases without post-stroke depression, and 109 controls without any evidence of post-stroke depression or cerebral infarction） to determine possible association between APOE rs429358 and rs7412 polymorphisms and risk of post-stroke depression. Our findings show no difference among the groups with regards genotype distribution of the rs7412 polymorphism. In contrast, APOE genotypes with rs429358-C alleles increased the risk of post-stroke depression. Further, the rs429358 polymorphism was associated with significantly decreased regional cerebral blood flow values in the left temporal lobe of post-stroke depression cases. Additionally, the rs429358 polymorphism was not only associated with depression severity, but with increasing serum levels of total cholesterol. These resuits suggest that the APOE rs429358 polymorphism is associated with increased risk of developing post-stroke depression, and that APOE rs429358-C allele genotypes may be detrimental to recovery of nerve function after stoke. Indeed, these findings provide clinical data for future post-stroke depression gene interventions.展开更多
Objective We aimed to investigate the cumulative effect of high CRP level and apolipoprotein B-to-apolipoprotein A-1（ApoB/ApoA-1） ratio on the incidence of ischemic stroke（IS） or coronary heart disease（CHD） in a...Objective We aimed to investigate the cumulative effect of high CRP level and apolipoprotein B-to-apolipoprotein A-1（ApoB/ApoA-1） ratio on the incidence of ischemic stroke（IS） or coronary heart disease（CHD） in a Mongolian population in China.Methods From June 2003 to July 2012,2589 Mongolian participants were followed up for IS and CHD events based on baseline investigation.All the participants were divided into four subgroups according to C-reactive protein（CRP） level and ApoB/ApoA-1 ratio.Cox proportional hazard models were used to estimate the hazard ratios（HRs） and 95% confidence intervals（CIs） for the IS and CHD events in all the subgroups.Results The HRs（95% CI） for IS and CHD were 1.33（0.84-2.12）,1.14（0.69-1.88）,and 1.91（1.17-3.11） in the ‘low CRP level with high ApoB/ApoA-1＇,‘high CRP level with low ApoB/ApoA-1＇,and ‘high CRP level with high ApoB/ApoA-1＇ subgroups,respectively,in comparison with the ‘low CRP level with low ApoB/ApoA-1＇ subgroup.The risks of IS and CHD events was highest in the ‘high CRP level with high ApoB/ApoA-1＇ subgroup,with statistical significance.Conclusion High CRP level with high ApoB/ApoA-1 ratio was associated with the highest risks of IS and CHD in the Mongolian population.This study suggests that the combination of high CRP and ApoB/ApoA-1 ratio may improve the assessment of future risk of developing IS and CHD in the general population.展开更多
Objective Apolipoprotein E （apoE） is associated with increased risk of age-related diseases, such as Alzheimer＇s disease （AD） and cerebrovascular disease （CVD）. The present study aims to investigate the age-rel...Objective Apolipoprotein E （apoE） is associated with increased risk of age-related diseases, such as Alzheimer＇s disease （AD） and cerebrovascular disease （CVD）. The present study aims to investigate the age-related general morphological changes of the brain in GFAP-apoE transgenic mice, especially the alterations in number and size of hippocampal pyramidal cells and the microvascular lesions in the thalamus. Methods Nine female apoE4/4 mice were divided into 3 groups （n=3 in each group）： 3-4 months （young group）, 9-10 months （middle-aged group） and 20-21 months （old group）. Age-matched apoE3/ 3 mice were employed as control group （n=3 in each group）. The paraffin sections of brain tissue were stained by 2 conventional staining methods, thionin staining and hematoxylin-esion（HE） staining, the former of which was to observe the hippocampal cells, while the latter was used to examine the brain microvasculature. Results There was no apparent difference in the cortical layer between apoE3/3 and apoE4/4 mice, neither any significant difference in the number of cells in hippocampal CA1-CA3 subfields between apoE3/3 and apoE4/4 mice at various age points （P 〉 0.05）. However, the mean size of pyramidal cells in CA1 subfield in apoE3/3 and apoE4/4 mice decreased as mice were getting older （P 〈 0.001）. At the age of 20-21 months, this cellular atrophy in apoE4/4 mice was more severe than that in old apoE3/3 mice （P 〈 0.05）. Furthermore, microvascular lesion in the thalamus was detected in all the 3 old apoE4/4 mice, at varying degrees （5.24%, 1.41% and 3.97%, respectively）, while only one apoE3/3 mouse exhibited microvascular lesion in the thalamus, at a low level （0.85%）. Conclusion The current study suggests that the cell size in hippocampal CA1 subfield decreases with aging, irrespective of apoE genotype. Cellular atrophy in CA1 subfield and the microvascular lesion in the thalamus are both more severe in old apoE4/4 mice as compared with those in age-matched apoE3/3 mice. Doubts still exist on whether the decreased cell size in hippocampal CA1 subfield in old apoE4/4 mice is associated with dysfunction in learning and memory and whether the microvascular lesions indicate a higher risk of stroke in human apoE4 allele mice. To clarify these issues, further investigations are needed.展开更多
文摘Complex genetic relationships between neurodegenerative disorders and neuropsychiatric symptoms have been shown, suggesting shared pathogenic mechanisms and emphasizing the potential for developing common therapeutic targets. Apolipoprotein E(APOE) genotypes and their corresponding protein(Apo E) isoforms may influence the biophysical properties of the cell membrane lipid bilayer. However, the role of APOE in central nervous system pathophysiology extended beyond its lipid transport function. In the present review article, we analyzed the links existing between APOE genotypes and the neurobiology of neuropsychiatric symptoms in neurodegenerative and vascular diseases. APOE genotypes(APOE ε2, APOE ε3, and APOE ε4) were implicated in common mechanisms underlying a wide spectrum of neurodegenerative diseases, including sporadic Alzheimer's disease, synucleinopathies such as Parkinson's disease and Lewy body disease, stroke, and traumatic brain injury. These shared pathways often involved neuroinflammation, abnormal protein accumulation, or responses to acute detrimental events. Across these conditions, APOE variants are believed to contribute to the modulation of inflammatory responses, the regulation of amyloid and tau pathology, as well as the clearance of proteins such as α-synuclein. The bidirectional interactions among Apo E, amyloid and mitochondrial metabolism, immunomodulatory effects, neuronal repair, and remodeling underscored the complexity of Apo E's role in neuropsychiatric symptoms associated with these conditions since from early phases of cognitive impairment such as mild cognitive impairment and mild behavioral impairment. Besides Apo E-specific isoforms' link to increased neuropsychiatric symptoms in Alzheimer's disease(depression, psychosis, aberrant motor behaviors, and anxiety, not apathy), the APOE ε4 genotype was also considered a significant genetic risk factor for Lewy body disease and its worse cognitive outcomes. Conversely, the APOE ε2 variant has been observed not to exert a protective effect equally in all neurodegenerative diseases. Specifically, in Lewy body disease, this variant may delay disease onset, paralleling its protective role in Alzheimer's disease, although its role in frontotemporal dementia is uncertain. The APOE ε4 genotype has been associated with adverse cognitive outcomes across other various neurodegenerative conditions. In Parkinson's disease, the APOE ε4 allele significantly impacted cognitive performance, increasing the risk of developing dementia, even in cases of pure synucleinopathies with minimal co-pathology from Alzheimer's disease. Similarly, in traumatic brain injury, recovery rates varied, with APOE ε4 carriers demonstrating a greater risk of poor long-term cognitive outcomes and elevated levels of neuropsychiatric symptoms. Furthermore, APOE ε4 influenced the age of onset and severity of stroke, as well as the likelihood of developing stroke-associated dementia, potentially due to its role in compromising endothelial integrity and promoting blood–brain barrier dysfunction.
基金financially supported by the Science and Technology Innovation Program of Hunan Province,No.2022RC1220(to WP)China Postdoctoral Science Foundation,No.2022M711733(to ZZ)+2 种基金the National Natural Science Foundation of China,No.82160920(to ZZ)Hebei Postdoctoral Scientific Research Project,No.B2022003040(to ZZ)Hunan Flagship Department of Integrated Traditional Chinese and Western Medicine(to WP)。
文摘Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment.Metabolic abnormalities are commonly observed in patients with Alzheimer's disease.The liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's disease.Notably,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease.In this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism.Furthermore,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.
基金supported by the Key Support Project of Regional Innovation and Development Joint Fund of National Natural Science Foundation of China(U20A20398)the National Natural Science Foundation of China(82104454,82374399)+1 种基金the Clinical Medical Research Transformation Project of Anhui Province(202304295107020111)the Natural Science Research Key Project of Anhui Provincial Department of Education(KJ2021A0542).
文摘Background:Chronic obstructive pulmonary disease(COPD)is a prevalent respiratory ailment that has risen to become the foremost cause of mortality globally,and statins are a widely used class of lipid-modifying drugs.Data from some observational studies suggest an association between statins use and COPD.Objectives:The main objective of this study was to investigate whether lipids and apolipoproteins are bidirectionally causally associated with COPD at the genetic level using a Mendelian randomization(MR)design,and to determine the potential role of circulating inflammatory proteins as mediators in this association.Methods:The publicly available Genome-Wide Association Study(GWAS)database was utilised for the purposes of the analysis.The data on high-density lipoprotein(HDL-C),low-density lipoprotein(LDL-C),triglycerides(TG),apolipoprotein A-1(ApoA1),and apolipoprotein B(ApoB)were obtained from the UK BioBank,while the COPD dataset was obtained from the FinnGen BioBank R11(number of cases:21,617,number of controls:372,627).Furthermore,data were gathered on genetic variants linked to inflammatory processes,encompassing 91 circulating inflammatory proteins(n=14,823 individuals).A two-sample MR study was conducted using these data to assess the association between HDL-C,LDL-C,TG,ApoA1,and ApoB with the risk of COPD.Furthermore,in order to investigate the potential mediating influence of inflammatory factor alterations between lipids and COPD,a two-step Mendelian randomization(MR)mediation analysis was conducted.Results:The forward MR methods identified two lipids that were found to have a causal relationship with the development of COPD.An elevated level of LDL-C and ApoB was found to be associated with a diminished risk of COPD.Furthermore,the researchers identified circulating inflammatory factors that were determined to be the causal agents in the development of COPD.Mediation analysis indicated that the inflammatory protein S100-A12 may act as a mediator between the LDL-C and COPD pathways.Conclusion:The present MR study provides genetic evidence for a causal relationship between lipids and apolipoproteins and COPD,as well as identifying the inflammatory protein S100-A12 as a potential mediator of the COPD association.The findings offer valuable insights into the mechanistic studies of statins for COPD and potential targets for disease intervention and treatment.
基金Supported by the China Postdoctoral Science Foundation General Program,No.2024M762504the Intramural Research Program of Liyuan Hospital,Tongji Medical College,Huazhong University of Science and Technology,No.2023 LYYYGZRP0004.
文摘BACKGROUND Apolipoprotein E epsilon 4(APOE4)is recognized as a genetic risk factor for cognitive decline and neurodegeneration in both type 2 diabetes mellitus(T2DM)and Alzheimer’s disease,while glycated hemoglobin(HbA1c)reflects persistent hyperglycemia and serves as a key indicator of long-term glycemic control in T2DM.Although both factors have been individually linked to neurobehavioral deficits,it remains uncertain whether HbA1c contributes to APOE4-related cognitive and olfactory impairment in individuals with T2DM.AIM To investigate the role of HbA1c in APOE4-associated cognitive and olfactory dysfunction in patients with T2DM.METHODS Of 636 T2DM patients were recruited from five medical centers in Wuhan,Hubei Province,China.APOE genotyping was evaluated by polymerase chain reaction using Gerard’s method.Cognitive and olfactory functions were assessed by mini-mental state examination and Connecticut chemosensory clinical research center test,respectively.Regression analysis was employed to assess the independent and interactive effects of HbA1c on APOE4-associated cognitive and olfactory function.RESULTS APOE4 was associated with increased risks of cognitive impairment[odds ratios(OR)=1.815,P=0.021]and olfactory dysfunction(OR=2.588,P<0.001).Higher HbA1c levels were also related to worse cognitive(OR=1.189,P<0.001)and olfactory performance(OR=1.149,P=0.011).HbA1c exerted a moderating effect,yet not a mediating effect,between APOE4 and its impacts on cognition and olfaction.Specifically,a higher level of HbA1c exacerbated the damaging effect of APOE4,as shown by significant interaction effects on both cognitive impairment(OR=2.687,P<0.001)and olfactory dysfunction(OR=1.440,P=0.027).CONCLUSION Elevated HbA1c levels are associated with increased risks of cognitive and olfactory impairments in patients with T2DM and may exacerbate the detrimental effects of APOE4.These findings underscore the need for early preventive strategies targeting individuals with both poor glycemic control and APOE4 carriage to mitigate neurodegenerative risk.
基金Supported by the Medical Science and Technology Project of Zhejiang Province,No.2022KY518General Scientific Research Project of Zhejiang Provincial Education Department,No.Y202352799Medical Science and Technology Project of Zhejiang Province,No.2024KY726.
文摘BACKGROUND Young-onset type 2 diabetes mellitus(T2DM)is associated with adverse health outcomes and increased mortality.Vitamin D(VitD)deficiency is likewise linked to various adverse health outcomes and is significantly associated with lipid metabolism in patients with T2DM.However,little is known regarding the me-chanisms of interaction between VitD and apolipoprotein A1(apoA1)in young-onset T2DM.AIM To evaluate the relationship between VitD and apoA1 levels in patients with young-onset T2DM.METHODS This cross-sectional study was conducted at Zhejiang Provincial People’s Hospital between January 2019 and December 2023.A total of 642 patients with T2DM who aged 18-40 years were included and matched with 642 individuals without diabetes(controls)based on age and sex.No specific intervention was applied,and data were collected from medical records and laboratory tests.The re-lationship between VitD and apoA1 levels was examined using Spearman’s correlation and logistic regression models.RESULTS We found that VitD levels were significantly lower in patients with T2DM compared to controls(15.9 ng/mL vs 17.4 ng/mL,P<0.001),with a notable positive correlation between VitD deficiency and reduced apoA1 levels.Multifactor logistic regression analysis identified that severe VitD deficiency was an independent risk factor for apoA1 in young-onset T2DM patients(odds ratio=3.43,95%confidence interval:1.16-10.20,β=1.23,P=0.026).CONCLUSION Our findings reveal an association between VitD and apoA1 in young-onset T2DM,suggesting that VitD may play a crucial role in metabolic regulation and cardiovascular risk management.
基金Supported by the National Natural Science Foundation of China,No.U1301227National Major Science and Technology Projects,No.2024ZD05209060Henan Province Jointly Built Science and Technology Key Projects,No.LHGJ20210337.
文摘BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a cancer with a poor prognosis,characterized by distinct geographical distribution and family clustering.AIM To investigate if ethnic differences(Han vs Kazakh)cause molecular variations in ESCC patients via genomic sequencing 299 samples.METHODS Here,we sequenced samples from 299 ESCC patients collected from Henan Key Laboratory for Esophageal Cancer Research and National Key Laboratory of Metabolic Dysregulation and Esophageal Cancer Prevention and Treatment,The First Affiliated Hospital of Zhengzhou University,including Han and Kazakh ethnic groups,and performed a genomic comparative analysis of these two ethnic cohorts.RESULTS ESCC patients of Kazakh ethnicity present with a later age of onset compared to Han.Kazakh patients exhibit a slightly higher tumor mutation burden compared to their Han counterparts.Three genes GIGYF1,CACNA1D,and ACOT11 exhibited mutation frequencies threefold higher in Kazakh patients than in Han.This enrichment may be associated with Kazakhs’adaptation to cold climates and consumption of high-calorie diets.Among Han patients,the apolipoprotein B messenger RNA-editing enzyme catalytic polypeptide(APOBEC)-associated single base substitutions(SBS)13 mutational signature is more prevalent,whereas SBS6,indicative of DNA mismatch repair deficiency,is more common in Kazakh patients.Additionally,Han Chinese patients with APOBEC-enriched tumors exhibit a significantly higher mutation load than those without.Moreover,patients lacking the APOBEC signature demonstrate superior survival probability compared to the APOBEC-enriched group.CONCLUSION Living environment and diet are major factors in the development of ESCC.Genomic difference may provide guidance for the formulation of clinical treatment plans for ESCC from different ethnics regions.
文摘Objective: To study the effects of Apolipoprotein E (ApoE) polymorphism onserum levels of lipids, lipoproteins and apolipoproteins. Methods: Fragments of ApoE gene forthex-on containing codon 112 and 158 polymorphic locus were amplified by PCR, and then digested untilCfo I endonuclease. Genotypes and alleles frequencies of 168 healthy persons in Jiangsu area werecalculated. The effects of ApoE genotypes and alleles on serum lipids, lipoproteins andapolipoproteins variation were analyzed. Results: The effects of ApoE alleles on total cholesterol(TC), law density lipoprotein-cholesterol (LDL-C), ApoB was: along a decreasing gradientε_4>ε_3>ε_2. The effect of ε_4 allele was to increase serum levels of TC, LDL-C and ApoB, andthe ε_2 allele had an effect opposite to that of ε_4 allele. Conclusion: ApoE polymorphism is anindependent genetic factor on individual serum levels of lipids and apolipoproteins.
文摘研究背景:研究证实阿司匹林对控制慢性血管疾病进展有显著效果,抗血小板药物应运而生。目前状况:抗血小板药物成为防治老年慢性疾病(chronic diseases of old age)不能或缺的常规性辅助治疗方案,阿司匹林、氯吡格雷、华法林、地奥斯明、利伐沙班等临床应用逐年增多,但效果参差不齐;同时,发生抗血小板药物抵抗或出血风险等不良反应的情况逐年增多,不但影响疗效,有些还威胁患者的生命,长期应用抗血小板药物的安全性问题可见一斑,安全有效的抗血小板方案备受关注。研究方法:对使用抗血小板药物的慢性血管疾病患者,观察其临床表现和治疗反应,检测其CYP2C19、APOE基因突变情况,用对照研究的方法探讨CYP2C19、APOE基因突变,慢性血管疾病临床表征及其与抗血小板药物反应的关系。结果和结论:CYP2C19和APOE基因突变在慢性血管疾病中可能有明确的临床特征,精准地掌控CYP2C19和APOE基因突变及其与临床药物精准靶点的关系,对慢性血管疾病的精准诊断和精准治疗都有现实意义。
基金supported by a grant from Grupos de Investigacion y Desarrollo Tecnologico de la Junta de Andalucía(Grupo consolidado CTS-159)
文摘BACKGROUND:Hypertriglyceridemia is an unusual cause of acute pancreatitis and sometimes considered to be an epiphenomenon.This study aimed to investigate the clinical and analytical features and the APOE genotypes in patients with acute pancreatitis and severe hypertriglyceridemia.METHODS:We undertook a one-year,prospective study of patients with acute pancreatitis whose first laboratory analysis on admission to the emergency department included measurement of serum triglycerides.The APOE genotype was determined and the patients answered an established questionnaire within the first 24 hours concerning their alcohol consumption,the presence of co-morbidities and any medications being taken.The patients’ progression,etiological diagnosis,hospital stay and clinical and radiological severity were all recorded.RESULTS:Hypertriglyceridemia was responsible for 7 of 133 cases of pancreatitis (5%);the remaining cases were of biliary (53%),idiopathic (26%),alcoholic (11%) or other (5%) origin.Compared with these remaining cases,the patients with hypertriglyceridemia were significantly younger,had more relapses,and more often had diabetes mellitus.They usually consumed alcohol or consumed it excessively on the days before admission.Also,the ε4 allele of the APOE gene was more common in this group (P<0.05).CONCLUSION:One of 20 episodes of acute pancreatitis is caused by hypertriglyceridemia and it is linked to genetic (ε4 allele) and comorbid factors such as diabetes and,especially,alcohol consumption.
基金Supported by a research grant of the Jurgen Manchot Stiftung
文摘AIM： To identify a multi serum protein pattern as well as single protein markers using surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry （SELDI-TOF-MS） for detection and differentiation of liver fibrosis （F1-F2）, liver cirrhosis （F4） and hepatocellular carcinoma （HCC） in patients with chronic hepatitis C virus （HCV）. METHODS： Serum samples of 39 patients with F1/F2 fibrosis, 44 patients with F4 fibrosis, 34 patients with HCC were applied to CM10 arrays and analyzed using the SELDI-TOF ProteinChip System （PBS-Ⅱc; Ciphergen Biosystems） after anion-exchange fractionation. All patients had chronic hepatitis C and histologically confirmed fibrosis stage/HCC. Data were analyzed for protein patterns by multivariate statistical techniques and artificial neural networks. RESULTS： A 4 peptide/protein multimarker panel （7486, 12843, 44293 and 53598 Da） correctly identified HCCs with a sensitivity of 100% and specificity of 85% in a two way-comparison of HCV-cirrhosis versus HCV-HCC training samples （AUROC 0.943）. Sensitivity and specificity for identification of HCC were 68% and 80% for random test samples. Cirrhotic patients could be discriminated against patients with F1 or F2 fibrosis using a 5 peptide/protein multimarker pattern （2873, 6646, 7775, 10525 and 67867 Da） with a specificity of 100% and a sensitivity of 85% in training samples （AUROC 0.976） and a sensitivity and specificity of 80% and 67% for random test samples. Combination of the biomarker classifiers with APR/score and alfa-fetopotein （AFP） improved the diagnostic performance. The 6646 Da marker protein for liver fibrosis was identified as apolipoprotein C-I. CONCLUSION： SELDI-TOF-MS technology combined with protein pattern analysis seems a valuable approach for the identification of liver cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis C. Host probably a combination of different serum markers will help to identify liver cirrhosis and early-stage hepatocellular carcinomas in the future.
基金Supported by PROFAPI-UAS and CECYT from Sinaloa, México
文摘AIM: To determine the possible association of the ApoB100 (Xba Ⅰ ), ApoE (Hha Ⅰ ) and CYP7A1 (Bsa Ⅰ ) gene polymorphisms, with the development of cholesterol gallstone disease (GD) in a Mexican population. METHODS: The polymorphisms were analyzed by polymerase chain reaction followed by restriction fragment length polymorphism, in two groups matched by ethnicity, age and sex: patients with GD (n = 101) and stone-free control subjects (n = 101). RESULTS: Allelic frequencies in patients and controls were: 34.16% vs 41.58% (P = 0.124) for X+of ApoB-100; 4.46% vs 5.94% (P = 0.501) for E2, 85.64% vs 78.22% (P = 0.052) for E3, 9.90% vs 15.84% (P = 0.075) for E4 of ApoE; and 25.74% vs 27.72% (P = 0.653) for C of CYP7A1. Differences in genotypic frequencies between the studied groups were not significant (P < 0.05). CONCLUSION: These results demonstrated that no association exists between the studied polymorphisms and cholelithiasis in this high prevalent population.
基金Supported by Zhongshan Hospital,Fudan University,Shanghai,China
文摘AIM:To prospectively investigate the association between the XbaⅠpolymorphisms of apolipoprotein B(APOB)gene and gallstone formation following gastrectomy.METHODS:The study was conducted between January 2005 and December 2006.A total of 186 gastric cancer patients who had undergone radical gastrectomy were grouped according to XbaⅠpolymorphisms of APOB gene(X+X-group,n=24 and X-X-group,n=162)and compared.The XbaⅠpolymorphisms of APOB gene were detected by polymerase chain reaction-restriction fragment length polymorphism(PCRRFLP).RESULTS:The incidence of gallstone was significantly higher in the X+X-group than in the X-X-group[54.2%vs 9.3%,RR=5.85(2.23-15.32),P<0.001].The serum levels of total cholesterol(TC)and low-density lipoprotein(LDL)were higher in the X+X-than in the X-X-group(4.02±1.12 vs 3.48±0.88,P=0.004 before surgery and 3.88±1.09 vs 3.40±0.86,P=0.008 after surgery).LDL was 2.21±0.96 vs 1.89±0.84(P=0.042)before surgery and 2.09±0.95 vs 1.72±0.85(P=0.029)after surgery in the two groups.No relationship was found between XbaⅠpolymorphisms and gallbladder motility.CONCLUSION:In Chinese patients after radical gastrectomy,X+allele of APOB gene is another risk factor for the development of gallstone besides the gallbladder motility disorder after surgery.
文摘Objective To examine the relationship between apolipoprotein E (Apo E) gene polymorphism and risk of coronary artery disease (CAD), analyzing association of polymorphism with classical risk factors. Methods A total of 124 patients (including 84 Han population and 40 Uygur population) with angiographically verified CAD or myocardial infarction were prospectively evaluated. Data referring to hypertension, diabetes, and tobacco consump-tion were recorded. The levels of total cholesterol (TC), high density lipoprotein (HDL) cholesterol, Apo A1 and B, and triglycerides (TG) were determined. DNA was obtained from 124 patients and 70 controls. In order to determine Apo E genotypes, DNA was PCR amplified and digested with HhaI. The genetic polymorphism of Apo E is due to three common alleles, epsilon(ε) 2, ε3, ε4, at a single autosomal gene locus. These alleles determine the six phenotypes E2/2, E3/3, E4/4, E4/2, E4/3, and E3/2. Results In Uygur population, the frequency of the ε2, ε3, and ε4 was 0.155, 0.648, and 0.197 respectively. In Han po-pulation, the frequency of the ε2, ε3, and ε4 was 0.081, 0.772, and 0.146 respectively. In the patient group, the frequency of the ε2, ε3, and ε4was 0.060, 0.758, and 0.182 respectively. In the control group, the frequency of the ε2, ε3, and ε4 was 0.193, 0.671, and 0.136 respectively. ε2 frequency of Uygur’ patients and controls was 0.050 and 0.290 respectively. Serum low density lipoprotein (LDL) cholesterol, TC, and TG values tended to decrease from the Apo E-4 phenotypes to Apo E-2 phenotypes. When deletion polymorphism of ε2 was compared with the common risk factors for CAD, its risk ratio (RR) is 4.38. Conclusions These studies confirm and find that Apo E phenotype distribution in Uygur population differs significantly from that in Han population in Xinjiang. CAD patients have significantly lower ε2 allele and slightly higher ε3 or ε4 allele frequency than controls, especially in Uygur population. It shows protective effects of ε2 on CAD.
文摘Hepatitis C virus(HCV) is a hepatotrophic virus and a major cause of chronic liver disease,including hepatocellular carcinoma,worldwide. The life cycle of HCV is closely associated with the metabolism of lipids and lipoproteins. The main function of lipoproteins is transporting lipids throughout the body. Triglycerides,free cholesterol,cholesteryl esters,and phospholipids are the major components of the transported lipids. The pathway of HCV assembly and secretion is closely linked to lipoprotein production and secretion,and the infectivity of HCV particles largely depends on the interaction of lipoproteins. Moreover,HCV entry into hepatocytes is strongly influenced by lipoproteins. The key lipoprotein molecules mediating these interactions are apolipoproteins. Apolipoproteins are amphipathic proteins on the surface of a lipoprotein particle,which help stabilize lipoprotein structure. They perform a key role in lipoprotein metabolism by serving as receptor ligands,enzyme co-factors,and lipid transport carriers. Understanding the association between the life cycle of HCV and lipoprotein metabolism is important because each step of the life cycle of HCV that is associated with lipoprotein metabolism is a potential target for anti-HCV therapy. In this article,we first concisely review the nature of lipoprotein and its metabolism to better understand the complicated interaction of HCV with lipoprotein. Then,we review the outline of the processes of HCV assembly,secretion,and entry into hepatocytes,focusing on the association with lipoproteins. Finally,we discuss the clinical aspects of disturbed lipid/lipoprotein metabolism and the significance of dyslipoproteinemia in chronic HCV infection with regard to abnormal apolipoproteins.
文摘AIM: To evaluate the tissular expression of Androgen (A), Estrogen (E) and Progesterone (Pg) receptors, and Apolipoprotein D (ApoD), in liver tumors from resected hepatocellular carcinoma (HCC) cases in order to assess their possible relationship to prognosis. METHODS: We performed an immunohistochemical study using tissue microarrays (containing more than 260 cancer specimens, from 31 HCC patients and controls) to determine the presence of specif ic antibodies against AR, ER, PgR and ApoD, correlating their findings with several clinico-pathological and biological variables. The staining results were categorized using a semi-quantitive score based on their intensity, and the percentage of immunostained cells was measured. RESULTS: A total of 21 liver tumors (67.7%) were positive for AR; 16 (51.6%) for ER; 26 (83.9%) for PgR and 12 (38.7%) stained for ApoD. We have found a wide variability in the immunostaining score values for each protein, with a median (range) of 11.5 (11.5-229.5) for AR; 11.1 (8.5-65) for ER; 14.2 (4-61) for PgR; and 37.7 (13.8-81.1) for ApoD. A history of heavy ethanol consumption, correlated positively with AR and PgR and negatively with ER status. HCV chronic infection also correlated positively with AR and PgR status. However, the presence of ApoD immunostaining did not correlate with any of these variables. Tumors with a positive immuno-staining for PgR showed a better prognosis. CONCLUSION: Our results indicate a moderate clinical value of the steroid receptor status in HCC, emphasizing the need to perform further studies in order to evaluate the possible role of new hormonal-based therapies.
基金supported in part by the National Natural Science Foundation of China,No.81160146
文摘Recent reports have shown that apolipoprotein E （APOE） polymorphisms are involved in neurodegenerative disease. However, it is unclear whether APOE affects post-stroke depression. Accordingly, we hypothesized that APOE polymorphisms modify the risk of post-stroke depression. Here, we performed a hospital-based case-control study （including 76 cerebral infarction cases with post-stroke depression, 88 cerebral infarction cases without post-stroke depression, and 109 controls without any evidence of post-stroke depression or cerebral infarction） to determine possible association between APOE rs429358 and rs7412 polymorphisms and risk of post-stroke depression. Our findings show no difference among the groups with regards genotype distribution of the rs7412 polymorphism. In contrast, APOE genotypes with rs429358-C alleles increased the risk of post-stroke depression. Further, the rs429358 polymorphism was associated with significantly decreased regional cerebral blood flow values in the left temporal lobe of post-stroke depression cases. Additionally, the rs429358 polymorphism was not only associated with depression severity, but with increasing serum levels of total cholesterol. These resuits suggest that the APOE rs429358 polymorphism is associated with increased risk of developing post-stroke depression, and that APOE rs429358-C allele genotypes may be detrimental to recovery of nerve function after stoke. Indeed, these findings provide clinical data for future post-stroke depression gene interventions.
基金supported by the National Natural Science Foundation of China(grant Nos.30972531 and 81320108026)a project of the Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘Objective We aimed to investigate the cumulative effect of high CRP level and apolipoprotein B-to-apolipoprotein A-1（ApoB/ApoA-1） ratio on the incidence of ischemic stroke（IS） or coronary heart disease（CHD） in a Mongolian population in China.Methods From June 2003 to July 2012,2589 Mongolian participants were followed up for IS and CHD events based on baseline investigation.All the participants were divided into four subgroups according to C-reactive protein（CRP） level and ApoB/ApoA-1 ratio.Cox proportional hazard models were used to estimate the hazard ratios（HRs） and 95% confidence intervals（CIs） for the IS and CHD events in all the subgroups.Results The HRs（95% CI） for IS and CHD were 1.33（0.84-2.12）,1.14（0.69-1.88）,and 1.91（1.17-3.11） in the ‘low CRP level with high ApoB/ApoA-1＇,‘high CRP level with low ApoB/ApoA-1＇,and ‘high CRP level with high ApoB/ApoA-1＇ subgroups,respectively,in comparison with the ‘low CRP level with low ApoB/ApoA-1＇ subgroup.The risks of IS and CHD events was highest in the ‘high CRP level with high ApoB/ApoA-1＇ subgroup,with statistical significance.Conclusion High CRP level with high ApoB/ApoA-1 ratio was associated with the highest risks of IS and CHD in the Mongolian population.This study suggests that the combination of high CRP and ApoB/ApoA-1 ratio may improve the assessment of future risk of developing IS and CHD in the general population.
基金supported by Outstanding Youth Teacher Fund of Anhui Province, China (No.2009SQRZ041ZD)
文摘Objective Apolipoprotein E （apoE） is associated with increased risk of age-related diseases, such as Alzheimer＇s disease （AD） and cerebrovascular disease （CVD）. The present study aims to investigate the age-related general morphological changes of the brain in GFAP-apoE transgenic mice, especially the alterations in number and size of hippocampal pyramidal cells and the microvascular lesions in the thalamus. Methods Nine female apoE4/4 mice were divided into 3 groups （n=3 in each group）： 3-4 months （young group）, 9-10 months （middle-aged group） and 20-21 months （old group）. Age-matched apoE3/ 3 mice were employed as control group （n=3 in each group）. The paraffin sections of brain tissue were stained by 2 conventional staining methods, thionin staining and hematoxylin-esion（HE） staining, the former of which was to observe the hippocampal cells, while the latter was used to examine the brain microvasculature. Results There was no apparent difference in the cortical layer between apoE3/3 and apoE4/4 mice, neither any significant difference in the number of cells in hippocampal CA1-CA3 subfields between apoE3/3 and apoE4/4 mice at various age points （P 〉 0.05）. However, the mean size of pyramidal cells in CA1 subfield in apoE3/3 and apoE4/4 mice decreased as mice were getting older （P 〈 0.001）. At the age of 20-21 months, this cellular atrophy in apoE4/4 mice was more severe than that in old apoE3/3 mice （P 〈 0.05）. Furthermore, microvascular lesion in the thalamus was detected in all the 3 old apoE4/4 mice, at varying degrees （5.24%, 1.41% and 3.97%, respectively）, while only one apoE3/3 mouse exhibited microvascular lesion in the thalamus, at a low level （0.85%）. Conclusion The current study suggests that the cell size in hippocampal CA1 subfield decreases with aging, irrespective of apoE genotype. Cellular atrophy in CA1 subfield and the microvascular lesion in the thalamus are both more severe in old apoE4/4 mice as compared with those in age-matched apoE3/3 mice. Doubts still exist on whether the decreased cell size in hippocampal CA1 subfield in old apoE4/4 mice is associated with dysfunction in learning and memory and whether the microvascular lesions indicate a higher risk of stroke in human apoE4 allele mice. To clarify these issues, further investigations are needed.
