Impact of apolipoprotein E isoforms on sporadic Alzheimer's disease:beyond the role of amyloid beta

The impact of apolipoprotein E(ApoE)isoforms on sporadic Alzheimer's disease has long been studied;however,the influences of apolipoprotein E gene(APOE)on healthy and pathological human brains are not fully understood.ApoE exists as three common isoforms(ApoE2,ApoE3,and ApoE4),which differ in two amino acid residues.Traditionally,ApoE binds cholesterol and phospholipids and ApoE isoforms display diffe rent affinities for their receptors,lipids transport and distribution in the brain and periphery.The role of ApoE in the human depends on ApoE isoforms,brain regions,aging,and neural injury.APOE E4 is the strongest genetic risk factor for sporadic Alzheimer's disease,considering its role in influencing amyloid-beta metabolism.The exact mechanisms by which APOE gene variants may increase or decrease Alzheimer's disease risk are not fully understood,but APOE was also known to affect directly and indirectly tau-mediated neurodegeneration,lipids metabolism,neurovascular unit,and microglial function.Consistent with the biological function of ApoE,ApoE4 isoform significantly alte red signaling pathways associated with cholesterol homeostasis,transport,and myelination.Also,the rare protective APOE variants confirm that ApoE plays an important role in Alzheimer's disease pathogenesis.The objectives of the present mini-review were to describe classical and new roles of various ApoE isoforms in Alzheimer's disease pathophysiology beyond the deposition of amyloid-beta and to establish a functional link between APOE,brain function,and memory,from a molecular to a clinical level.APOE genotype also exerted a heterogeneous effect on clinical Alzheimer's disease phenotype and its outcomes.Not only in learning and memory but also in neuro psychiatric symptoms that occur in a premorbid condition.Cla rifying the relationships between Alzheimer's disease-related pathology with neuropsychiatric symptoms,particularly suicidal ideation in Alzheimer's disease patients,may be useful for elucidating also the underlying pathophysiological process and its prognosis.Also,the effects of anti-amyloid-beta drugs,recently approved for the treatment of Alzheimer's disease,could be influenced by the APOE genotype.

27-Hydroxycholesterol/liver X receptor/apolipoprotein E mediates zearalenone-induced intestinal immunosuppression:A key target potentially linking zearalenone and cancer

Zearalenone(ZEN)is a mycotoxin that extensively contaminates food and feed,posing a significant threat to public health.However,the mechanisms behind ZEN-induced intestinal immunotoxicity remain unclear.In this study,Sprague-Dawley(SD)rats were exposed to ZEN at a dosage of 5 mg/kg/day b.w.for a duration of 14 days.The results demonstrated that ZEN exposure led to notable pathological alterations and immunosuppression within the intestine.Furthermore,ZEN exposure caused a significant reduction in the levels of apolipoprotein E(ApoE)and liver X receptor(LXR)(P<0.05).Conversely,it upregulated the levels of myeloid-derived suppressor cells(MDSCs)markers(P<0.05)and decreased the presence of 27-hydroxycholesterol(27-HC)in the intestine(P<0.05).It was observed that ApoE or LXR agonists were able to mitigate the immunosuppressive effects induced by ZEN.Additionally,a bioinformatics analysis highlighted that the downregulation of ApoE might elevate the susceptibility to colorectal,breast,and lung cancers.These findings underscore the crucial role of the 27-HC/LXR/ApoE axis disruption in ZEN-induced MDSCs proliferation and subsequent inhibition of T lymphocyte activation within the rat intestine.Notably,ApoE may emerge as a pivotal target linking ZEN exposure to cancer development.

Hepatocyte growth factor enhances the ability of dental pulp stem cells to ameliorate atherosclerosis in apolipoprotein E-knockout mice

BACKGROUND Atherosclerosis(AS),a chronic inflammatory disease of blood vessels,is a major contributor to cardiovascular disease.Dental pulp stem cells(DPSCs)are capable of exerting immunomodulatory and anti-inflammatory effects by secreting cytokines and exosomes and are widely used to treat autoimmune and inflam-mation-related diseases.Hepatocyte growth factor(HGF)is a pleiotropic cytokine that plays a key role in many inflammatory and autoimmune diseases.AIM To modify DPSCs with HGF(DPSC-HGF)and evaluate the therapeutic effect of DPSC-HGF on AS using an apolipoprotein E-knockout(ApoE-/-)mouse model and an in vitro cellular model.METHODS ApoE-/-mice were fed with a high-fat diet(HFD)for 12 wk and injected with DPSC-HGF or Ad-Null modified DPSCs(DPSC-Null)through tail vein at weeks 4,7,and 11,respectively,and the therapeutic efficacy and mechanisms were analyzed by histopathology,flow cytometry,lipid and glucose measurements,real-time reverse transcription polymerase chain reaction(RT-PCR),and enzyme-linked immunosorbent assay at the different time points of the experiment.An in vitro inflammatory cell model was established by using RAW264.7 cells and human aortic endothelial cells(HAOECs),and indirect co-cultured with supernatant of DPSC-Null(DPSC-Null-CM)or DPSC-HGF-CM,and the effect and mechanisms were analyzed by flow cytometry,RT-PCR and western blot.Nuclear factor-κB(NF-κB)activators and inhibitors were also used to validate the related signaling pathways.RESULTS DPSC-Null and DPSC-HGF treatments decreased the area of atherosclerotic plaques and reduced the expression of inflammatory factors,and the percentage of macrophages in the aorta,and DPSC-HGF treatment had more pronounced effects.DPSCs treatment had no effect on serum lipoprotein levels.The FACS results showed that DPSCs treatment reduced the percentages of monocytes,neutrophils,and M1 macrophages in the peripheral blood and spleen.DPSC-Null-CM and DPSC-HGF-CM reduced adhesion molecule expression in tumor necrosis factor-αstimulated HAOECs and regulated M1 polarization and inflammatory factor expression in lipopolysaccharide-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway.CONCLUSION This study suggested that DPSC-HGF could more effectively ameliorate AS in ApoE-/-mice on a HFD,and could be of greater value in stem cell-based treatments for AS.

New insights into ATR inhibition in muscle invasive bladder cancer:The role of apolipoprotein B mRNA editing catalytic subunit 3B

Background:Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC),an endogenous mutator,induces DNA damage and activates the ataxia telangiectasia and Rad3-related(ATR)-checkpoint kinase 1(Chk1)pathway.Although cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer(MIBC),it has a poor survival rate.Therefore,this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B(APOBEC3B)expressing MIBC.Methods:Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with MIBC.The APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot analysis.Western blot analysis was performed to confirm differences in phosphorylated Chk1(pChk1)expression according to the APOBEC3B expression.Cell viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with cisplatin.Results:There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with MIBC.Cells with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B levels.Combination treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B expression.Compared to cisplatin single treatment,combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B expression.Conclusion:Our study shows that APOBEC3B’s higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR inhibition.This result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.

Ferroptosis mechanism and Alzheimer's disease

Regulated cell death is a genetically determined form of programmed cell death that commonly occurs during the development of living organisms.This process plays a crucial role in modulating homeostasis and is evolutionarily conserved across a diverse range of living organisms.Ferroptosis is a classic regulatory mode of cell death.Extensive studies of regulatory cell death in Alzheimer’s disease have yielded increasing evidence that fe rroptosis is closely related to the occurrence,development,and prognosis of Alzheimer’s disease.This review summarizes the molecular mechanisms of ferroptosis and recent research advances in the role of ferro ptosis in Alzheimer’s disease.Our findings are expected to serve as a theoretical and experimental foundation for clinical research and targeted therapy for Alzheimer’s disease.

Isoform-and cell-state-specific APOE homeostasis and function

Apolipoprotein E is the major lipid transporter in the brain and an important player in neuron-astrocyte metabolic coupling.It ensures the survival of neurons under stressful conditions and hyperactivity by nourishing and detoxifying them.Apolipoprotein E polymorphism,combined with environmental stresses and/or age-related alterations,influences the risk of developing late-onset Alzheimer’s disease.In this review,we discuss our current knowledge of how apolipoprotein E homeostasis,i.e.its synthesis,secretion,degradation,and lipidation,is affected in Alzheimer’s disease.

Associations between physical activity levels and ATPase inhibitory factor 1 concentrations in older adults

Background:Adenosine triphosphatase inhibitory factor 1(IF1)is a key protein involved in energy metabolism.IF1 has been linked to various agerelated diseases,although its relationship with physical activity(PA)remains unclear.Additionally,the apolipoprotein A-I(apoA-I),a PA-modulated lipoprotein,could play a role in this relationship because it shares a binding site with IF1 on the cell-surface ATP synthase.We examined here the associations between chronic PA and plasma IF1 concentrations among older adults,and we investigated whether apoA-I mediated these associations.Methods:In the present work,1096 healthy adults(63.8%females)aged 70 years and over who were involved in the Multidomain Alzheimer Prevention Trial study were included.IF1 plasma concentrations(square root of ng/mL)were measured at the 1-year visit of the Multidomain Alzheimer Prevention Trial,while PA levels(square root of metabolic equivalent task min/week)were assessed using questionnaires administered each year from baseline to the 3-year visit.Multiple linear regressions were performed to investigate the associations between the first-year mean PA levels and IF1 concentrations.Mediation analyses were conducted to examine whether apoA-I mediated these associations.Mixedeffect linear regressions were carried out to investigate whether the 1-year visit IF1 concentrations predicted subsequent changes in PA.Results:Multiple linear regressions indicated that first-year mean PA levels were positively associated with IF1 concentrations(B=0.021;SE=0.010;p=0.043).Mediation analyses revealed that about 37.7%of this relationship was mediated by apoA-I(B_(ab)=0.008;SE=0.004;p=0.023).Longitudinal investigations demonstrated that higher concentrations of IF1 at the 1-year visit predicted a faster decline in PA levels over the subsequent 2 years(time×IF1:B=0.148;SE=0.066;p=0.025).Conclusion:This study demonstrates that regular PA is associated with plasma IF1 concentrations,and it suggests that apoA-I partly mediates this association.Additionally,this study finds that baseline concentrations of IF1 can predict future changes in PA.However,further research is needed to fully understand the mechanisms underlying these observations.

Liver as a new target organ in Alzheimer's disease:insight from cholesterol metabolism and its role in amyloid-beta clearance

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.

Apolipoprotein E2 inhibits mitochondrial apoptosis in pancreatic cancer cells through ERK1/2/CREB/BCL-2 signaling

Background: Apolipoprotein E2(ApoE2) is a pleiotropic protein that influences several aspects of cancer metabolism and development. Evading apoptosis is a vital factor for facilitating cancer cell growth. However, the role and mechanism of ApoE2 in regulating cell apoptosis of pancreatic cancer remain unclear. Methods: In this study, we firstly detected the m RNA and protein expressions of ApoE2 in PANC-1 and Capan-2 cells by real-time polymerase chain reaction and Western blotting. We then performed TUNEL and flow cytometric analyses to explore the role of recombinant human ApoE2, p CMV6-ApoE2 and si ApoE2 in the apoptosis of PANC-1 and Capan-2 cells. Furthermore, we investigated the molecular mechanism through which ApoE2 affected apoptosis in PANC-1 cells using immunofluorescence, immunoprecipitation, Western blotting and co-immunoprecipitation analysis. Results: ApoE2 phosphorylated ERK1/2 and inhibited pancreatic cancer cell apoptosis. In addition, our data showed that ApoE2/ERK1/2 altered the expression and mitochondrial localization of BCL-2 via activating CREB. ApoE2/ERK1/2/CREB also increased the total BCL-2/BAX ratio, inhibited the opening of the mitochondrial permeability transition pore and the depolarization of mitochondrial transmembrane potential, blocked the leakage of cytochrome-c and the formation of the apoptosome, and consequently, suppressed mitochondrial apoptosis. Conclusions: ApoE2 regulates the mitochondrial localization and expression of BCL-2 through the activation of the ERK1/2/CREB signaling cascade to evade the mitochondrial apoptosis of pancreatic cancer cells. ApoE2 may be a distinct prognostic marker and a potential therapeutic target for pancreatic cancer.

Seed-Specific Expression of Apolipoprotein A-IMilano Dimer in Engineered Rice Lines

Apolipoprotein A-IMilano(ApoA-IM)has been shown to significantly reduce coronary atherosclerotic plaques.However,the preparation of cost-effective pharmaceutical formulations of ApoA-IM is limited by the high cost and difficulty of purifying the protein and producing the highly effective dimeric form.The aim of this study was to create an expression cassette that specifically drives the expression of dimeric ApoA-IM in the protein bodies of rice seeds.The ApoA-IM protein under control of the 13 kDa prolamin promoter is expressed exclusively in its dimeric form within the seeds,and immunocytochemical and immunogold analyses confirmed its expression in different caryopsis tissue such as seed coat,aleurone cell and endosperm,particularly in amyloplast and storage vacuoles.A plant-based ApoA-IM production system offered numerous advantages over current production systems,including the direct production of the most therapeutically effective dimeric ApoA-IM forms,long-term protein storage in seeds,and ease of protein production by simply growing plants.Therefore,seeds had the potential to serve as a costeffective source of therapeutic ApoA-IM.

Apolipoprotein A1 suppresses the hypoxia-induced angiogenesis of human retinal endothelial cells by targeting PlGF

AIM:To investigate the anti-angiogenic effect of apolipoprotein A1(apoA1)on primary human retinal vascular endothelial cells(HRECs)and explore the possible mechanism.METHODS:The primary HRECs were transfected with apoA1-GFP recombinant lentiviral and were compared with cells undergoing transfection with empty lentiviral vectors.Hypoxia chambers were used to simulate the anoxic environment of cells under pathological condition.The concentrations of secreted vascular endothelial growth factor(VEGF)and placental growth factor(PlGF)were measured by enzyme-linked immunosorbent assay(ELISA).Cell migration ability was detected by wound healing assay.The sprouting of HRECs was determined by tube formation assay.The protein levels of extracellular signal regulated kinase 1/2(ERK1/2)and phosphor ylated ERK1/2(p-ERK1/2)were measured by Western blot.RESULTS:Overexpressed apoA1 in hypoxia-induced HRECs significantly suppressed PlGF(0.67±0.10 folds,P=0.007).Overexpressed apoA1 also attenuated hypoxiainduced cell migration(0.32±0.11 folds,P<0.0001),tube formation(0.66±0.01 folds,P<0.0001)and the phosphorylation levels of ERK(0.6±0.11 folds,P=0.025).Pretreatment of mitogen-activated protein kinase kinase(MEK)inhibitor(U0126)further reduced the PlGF and angiogenesis in hypoxia-induced HRECs.CONCLUSION:ApoA 1 inhibits the angiogenesis at least in part by inactivating ERK1/2 in hypoxia-induced HRECs.Moreover,apoA1 suppresses the PlGF expression,which selectively associated with pathological angiogenesis.

Apolipoprotein C1 promotes tumor progression in gastric cancer

Background:Gastric cancer(GC)is a malignancy with the worst prognosis that seriously threatens human health,especially in East Asia.Apolipoprotein C1(apoc1)belongs to the apolipoprotein family.In addition,apoc1 has been associated with various tumors.However,its role in GC remains unclear.Methods:Firstly,we quantified its expression in GC and adjacent tumor tissues,using The Cancer Genome Atlas(TCGA).Next,we assessed cell invasion and migration abilities.Finally,we revealed the role of apoc1 in the tumor microenvironment(TME),immune cell infiltration and drug sensitivity.Results:Firstly,in TCGA database,it has been shown that elevated expression of apoc1 was identified in various cancers,including GC,then we found that high expression of apoc1 was significantly correlated with poor prognosis in GC.Histologically,apoc1 expression is proportional to grade,cancer stage,and T stage.The experimental results showed that apoc1 promoted cell invasion and migration.Then GO,KEGG,and GSEA pathway analyses indicated that apoc1 may be involved in the WNT pathway and immune regulation.Furthermore,we found out the tumor-infiltrating immune cells related to apoc1 in the tumor microenvironment(TME)using TIMER.Finally,we investigated the correlation between apoc1 expression and drug sensitivity,PD-1 and CTLA-4 therapy.Conclusions:These results suggest that apoc1 participates in the evolution of GC,and may represent a potential target for detection and immunotherapy in GC.

Association of apolipoprotein E gene polymorphism with the occurrence and therapeutic effect of ischemic stroke

At present,ischemic stroke seriously affects people's life and health,and its occurrence,development and therapeutic effect are affected by many factors.With the deep research on ischemic cerebral apoplexy disease,people have a deeper understanding of its virulence genes.The apolipoprotein E genotype is the research focus recently,its genetic type is not only involved in the occurrence and development of ischemic cerebral apoplexy,but also causes different therapeatic effects.In this paper,we reviewed the relationship between apolipoprotein E gene polymorphism and lipid metabolism and atherosclerosis in ischemic stroke,as well as the differences in the therapeutic effects of thrombolysis,thrombectomy and lipid-lowering among different genotypes.

The Effects of Apolipoprotein E Polymorphism on Serum Lipids, Lipoproteins and Apolipoproteins Variation

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.

Replacement of leisure-time sedentary behavior with various physical activities and the risk of dementia incidence and mortality:A prospective cohort study

Background:Whether or not there is targeted pharmacotherapy for dementia,an active and healthy lifestyle that includes physical activity(PA)may be a better option than medication for preventing dementia.We examined the association between leisure-time sedentary behavior(SB)and the risk of dementia incidence and mortality.We further quantified the effect on dementia risk of replacing sedentary time with an equal amount of time spent on different physical activities.Methods:In the UK Biobank,484,169 participants(mean age=56.5 years;45.2%men)free of dementia were followed from baseline(2006-2010)through July 30,2021.A standard questionnaire measured individual leisure-time SB(watching TV,computer use,and driving)and PA(walking for pleasure,light and heavy do-it-yourself activity,strenuous sports,and other exercise)frequency and duration in the 4 weeks prior to evaluation.Apolipoprotein E(APOE)genotype data were available for a subset of 397,519(82.1%)individuals.A Cox proportional hazard model and an isotemporal substitution model were used in this study.Results:During a median 12.4 years of follow-up,6904 all-cause dementia cases and 2115 deaths from dementia were recorded.In comparison to participants with leisure-time SB<5 h/day,the hazard ratio((HR),95%confidence interval(95%CI))of dementia incidence was 1.07(1.02-1.13)for 5-8 h/day and 1.25(1.13-1.38)for>8 h/day,and the HR of dementia mortality was 1.35(1.12-1.61)for>8 h/day.A 1 standard deviation increment of sedentary time(2.33 h/day)was strongly associated with a higher incidence of dementia and mortality(HR=1.06,95%CI:1.03-1.08 and HR=1.07,95%CI:1.03-1.12,respectively).The association between sedentary time and the risk of developing dementia was more profound in subjects<60 years than in those>60 years(HR=1.26,95%CI:1.00-1.58 vs.HR=1.21,95%CI:1.08-1.35 in>8 h/day,p for interaction=0.013).Replacing 30 min/day of leisure sedentary time with an equal time spent in total PA was associated with a6%decreased risk and 9%decreased mortality from dementia,with exercise(e.g.,swimming,cycling,aerobics,bowling)showing the strongest benefit(HR=0.82,95%CI:0.78-0.86 and HR=0.79,95%CI:0.72-0.86).Compared with APOEε4 noncarriers,APOEε4 carriers are more likely to see a decrease in Alzheimer’s disease incidence and mortality when PA is substituted for SB.Conclusion:Leisure-time SB was positively associated with the risk of dementia incidence and mortality.Replacing sedentary time with equal time spent doing PA may be associated with a significant reduction in dementia incidence and mortality risk.

Triglyceride levels and apolipoprotein E polymorphism in patients with acute pancreatitis

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.

XbaⅠpolymorphisms of apolipoprotein B gene:Another risk factor of gallstone formation after radical gastrectomy

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.

APOLIPOPROTEIN E GENE POLYMORPHISMS AND RISK FOR CORONARY ARTERY DISEASE IN CHINESE XINJIANGUYGUR AND HAN POPULATION

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.

Liver expression of steroid hormones and Apolipoprotein D receptors in hepatocellular carcinoma

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.

Apolipoprotein E polymorphisms increase the risk of post-stroke depression

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.