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Pathogens (Basel, Switzerland) Jun 2024This study investigates the impact of Epstein-Barr virus (EBV) infection on children's proteomes across different phases of the disease, utilising seventy-nine blood...
This study investigates the impact of Epstein-Barr virus (EBV) infection on children's proteomes across different phases of the disease, utilising seventy-nine blood samples categorised into three groups: EBV-naive patients, acute infectious mononucleosis (IM) cases, and convalescents followed up for 12 months post-IM. The aim is to identify proteins influenced by EBV infection, shedding light on the chronic processes triggered by the virus. The results reveal thirty-nine proteins distinguishing between naive patients and those with IM, including actin, lumican, peroxiredoxin-2, fibulin-1, gelsolin, and alpha-2-macroglobulin, which are involved in immune responses, cell adhesion, and inflammation. Elevated oxidative stress markers like peroxiredoxin-2 in IM patients suggest potential links to EBV's induction of reactive oxygen species. Increased levels of apolipoproteins A-I, A-IV, C-IV, and M during IM imply associations with viral infection, while complement system proteins (C1q, C1r, and C8 gamma chain) are also elevated, reflecting their role in the immune response and viral clearance. This study's focus on children provides unique insights into EBV's impact on young populations, emphasising proteomics' role in uncovering protein associations and understanding the virus's long-term consequences. However, specific relationships between identified proteins and EBV infection require further investigation.
PubMed: 38921769
DOI: 10.3390/pathogens13060471 -
Apolipoprotein A-I levels in the survival of patients with colorectal cancer: a retrospective study.Frontiers in Endocrinology 2024Abnormal lipid levels have been associated with cancer incidence and progression. However, limited studies have investigated the relationship between apolipoprotein A-I...
BACKGROUND
Abnormal lipid levels have been associated with cancer incidence and progression. However, limited studies have investigated the relationship between apolipoprotein A-I (ApoA-I) and colorectal cancer (CRC). This study assessed the significance of ApoA-I levels in progression-free survival (PFS) and overall survival (OS) of patients with CRC.
METHODS
Survival curves were compared using Kaplan-Meier analysis, while the predictive values of various lipid indicators in CRC prognosis were evaluated based on receiver operating characteristic curves. The factors influencing PFS and OS in patients with CRC were analyzed using Cox proportional hazards regression models. Finally, the relationship between ApoA-I level and disease recurrence was investigated through logistic regression analysis. The optimal Apo-I level was determined through maximally selected rank statistics.
RESULTS
Using the optimal ApoA-I cutoff value (0.9 g/L), the 1,270 patients with CRC were categorized into low (< 0.9 g/L, 275 cases) and high (≥0.9 g/L, 995 cases) ApoA-I groups. Compared with other lipid indicators, ApoA-I demonstrated superior predictive accuracy. The high ApoA-I group exhibited significantly higher survival rates than the low ApoA-I group (PFS, 64.8% vs. 45.2%, < 0.001; OS, 66.1% vs. 48.6%, < 0.001). Each one-standard-deviation increase in ApoA-I level was related to a 12.0% decrease in PFS risk (hazard ratio [HR] 0.880; 95% confidence interval [CI], 0.801-0.968; = 0.009) and an 11.2% decrease in OS risk (HR 0.888; 95%CI, 0.806-0.978; = 0.015). Logistic regression analysis revealed that patients with low ApoA-I had a 32.5% increased risk of disease recurrence (odds ratio [OR] 0.675; 95%CI, 0.481-0.946; = 0.0225) compared with those with high ApoA-I. PFS/OS nomograms based on ApoA-I demonstrated excellent prognostic prediction accuracy.
CONCLUSIONS
Serum ApoA-I level may be a valuable and non-invasive tool for predicting PFS and OS in patients with CRC.
Topics: Humans; Apolipoprotein A-I; Colorectal Neoplasms; Male; Female; Middle Aged; Retrospective Studies; Aged; Prognosis; Biomarkers, Tumor; Survival Rate; Adult; Kaplan-Meier Estimate
PubMed: 38919478
DOI: 10.3389/fendo.2024.1318416 -
BMC Cardiovascular Disorders Jun 2024This study investigated the possible relationship between the Apo lipoprotein A1 /high-density lipoprotein cholesterol (ApoA1/HDL-C) ratio and coronary artery disease...
INTRODUCTION
This study investigated the possible relationship between the Apo lipoprotein A1 /high-density lipoprotein cholesterol (ApoA1/HDL-C) ratio and coronary artery disease (CAD) in patients with type 2 diabetes (T2D).
METHODS
This was a matched case-control study of 482 patients with T2D in two groups of CAD and (n = 241) non-CAD (n = 241). The patients were classified into four quartiles according to the ApoA1/HDL-C ratio, and multivariate logistic regression analysis was performed to assess the relationship between ApoA1/HDL-C and CAD. ROC analysis was also conducted.
RESULTS
This study showed that the ApoA1/HDL-C ratio has an independent association with CAD in individuals with T2D. The CAD group exhibited a significantly higher ApoA1/HDL-C ratio than those without CAD (p-value = 0.004). Moreover, the risk of CAD increased significantly across the ApoA1/HDL-C ratio quartiles, with the highest odds in the fourth quartile. The second quartile showed an odds ratio (OR) of 2.03 (p-value = 0.048) compared to the first. Moving to the third quartile, the OR increased to 2.23 (p-value = 0.023). The highest OR was noted in the fourth, reaching 3.41 (p-value = 0.001). Employing a cut-off value of 2.66 and an area under the curve (AUC) of 0.885, the ApoA1/HDL-C ratio predicts CAD among patients with T2D with a sensitivity of 75% and a specificity of 91% (p-value < 0.001).
CONCLUSION
The current study revealed an independent association between ApoA1/HDL-C ratio and CAD in patients with T2D. This ratio can be a promising tool for predicting CAD during the follow-up of patients with T2D, aiding in identifying those at higher risk for CAD.
Topics: Humans; Diabetes Mellitus, Type 2; Apolipoprotein A-I; Coronary Artery Disease; Male; Female; Middle Aged; Cholesterol, HDL; Case-Control Studies; Aged; Biomarkers; Predictive Value of Tests; Risk Assessment; Risk Factors; Prognosis
PubMed: 38914982
DOI: 10.1186/s12872-024-03986-w -
Journal of Cellular and Molecular... Jun 2024Our previous study reckons that the impact of the rs1801133 variant of 5,10-methylenetetrahydrofolate reductase (MTHFR) on coronary artery disease (CAD) is possibly...
Our previous study reckons that the impact of the rs1801133 variant of 5,10-methylenetetrahydrofolate reductase (MTHFR) on coronary artery disease (CAD) is possibly mediated by cardiometabolic disorder. This study is performed to verify this hypothesis. Four hundred and thirty CAD patients and 216 CAD-free individuals were enrolled in this case-control study. The rs1801133 variant was genotyped by PCR-RFLP. Severity of coronary lesions was evaluated by number of stenotic coronary vessels and extent of coronary stenosis. The rs1801133 T allele significantly increased homocysteine levels in patients with CAD and CAD-free individuals. Individuals with the T allele of rs1801133 had an increased risk of developing CAD. In contrast, individuals with the TT genotype of rs1801133 were at high risk of multiple vessel lesions. The carriers of CT genotype had higher levels of systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), and high-sensitivity C-reactive protein (hs-CRP), and lower levels of apolipoprotein A1 (APOA1) than those with CC genotype in male patients with CAD. The receiver operating characteristic (ROC) curve and precision-recall (PR) curve indicated that hyperhomocysteinemia was sensitive to predict the severity of CAD. Multivariate logistic regression revealed that homocysteine, rs1801133, age, smoking, weight, body mass index (BMI), lipoprotein(a) [Lp(a)], and hs-CRP were independent risk factors for CAD. The increased risk of CAD and severity of coronary lesions associated with rs1801133 in the Chinese Han population were attributed, at least partly, to high homocysteine levels. Hyperhomocysteinemia had a high predictive value for severe CAD or multiple vessel lesions.
Topics: Humans; Homocysteine; Male; Coronary Artery Disease; Middle Aged; Female; Case-Control Studies; Methylenetetrahydrofolate Reductase (NADPH2); Polymorphism, Single Nucleotide; Severity of Illness Index; Aged; Risk Factors; Genetic Predisposition to Disease; ROC Curve; Genotype; C-Reactive Protein; Alleles; Apolipoprotein A-I
PubMed: 38896027
DOI: 10.1111/jcmm.18474 -
Medicine Jun 2024The objective of the current study is to assess the usefulness of HbA1cAp ratio in predicting in-hospital major adverse cardiac events (MACEs) among acute ST-segment... (Observational Study)
Observational Study
Establishment and validation of nomogram model for predicting major adverse cardiac events in patients with acute ST-segment elevation myocardial infarction based on glycosylated hemoglobin A1c to apolipoprotein A1 ratio: An observational study.
The objective of the current study is to assess the usefulness of HbA1cAp ratio in predicting in-hospital major adverse cardiac events (MACEs) among acute ST-segment elevation myocardial infarction (STEMI) patients that have undergone percutaneous coronary intervention (PCI). Further, the study aims to construct a ratio nomogram for prediction with this ratio. The training cohort comprised of 511 STEMI patients who underwent emergency PCI at the Huaibei Miners' General Hospital between January 2019 and May 2023. Simultaneously, 384 patients treated with the same strategy in First People's Hospital of Hefei formed the validation cohort during the study period. LASSO regression was used to screen predictors of nonzero coefficients, multivariate logistic regression was used to analyze the independent factors of in-hospital MACE in STEMI patients after PCI, and nomogram models and validation were established. The LASSO regression analysis demonstrated that systolic blood pressure, diastolic blood pressure, D-dimer, urea, and glycosylated hemoglobin A1c (HbA1c)/apolipoprotein A1 (ApoA1) were significant predictors with nonzero coefficients. Multivariate logistic regression analysis was further conducted to identify systolic blood pressure, D-dimer, urea, and HbA1c/ApoA1 as independent factors associated with in-hospital MACE after PCI in STEMI patients. Based on these findings, a nomogram model was developed and validated, with the C-index in the training set at 0.77 (95% CI: 0.723-0.817), and the C-index in the validation set at 0.788 (95% CI: 0.734-0.841), indicating excellent discrimination accuracy. The calibration curves and clinical decision curves also demonstrated the good performance of the nomogram models. In patients with STEMI who underwent PCI, it was noted that a higher HbA1c of the ApoA1 ratio is significantly associated with in-hospital MACE. In addition, a nomogram is constructed having considered the above-mentioned risk factors to provide predictive information on in-hospital MACE occurrence in these patients. In particular, this tool is of great value to the clinical practitioners in determination of patients with a high risk.
Topics: Humans; Nomograms; ST Elevation Myocardial Infarction; Male; Female; Apolipoprotein A-I; Middle Aged; Glycated Hemoglobin; Percutaneous Coronary Intervention; Aged; Risk Assessment; Logistic Models; Risk Factors
PubMed: 38875361
DOI: 10.1097/MD.0000000000038563 -
Journal of Medical Case Reports Jun 2024Homozygous mutations in the APOA5 gene constitute a rare cause of monogenic hypertriglyceridemia, or familial chylomicronemia syndrome (FCS). We searched PubMed and...
BACKGROUND
Homozygous mutations in the APOA5 gene constitute a rare cause of monogenic hypertriglyceridemia, or familial chylomicronemia syndrome (FCS). We searched PubMed and identified 16 cases of homozygous mutations in the APOA5 gene. Severe hypertriglyceridemia related to monogenic mutations in triglyceride-regulating genes can cause recurrent acute pancreatitis. Standard therapeutic approaches for managing this condition typically include dietary interventions, fibrates, and omega-3-fatty acids. A novel therapeutic approach, antisense oligonucleotide volanesorsen is approved for use in patients with FCS.
CASE PRESENTATION
We report a case of a 25-years old Afghani male presenting with acute pancreatitis due to severe hypertriglyceridemia up to 29.8 mmol/L caused by homozygosity in APOA5 (c.427delC, p.Arg143Alafs*57). A low-fat diet enriched with medium-chain TG (MCT) oil and fibrate therapy did not prevent recurrent relapses, and volanesorsen was initiated. Volanesorsen resulted in almost normalized triglyceride levels. No further relapses of acute pancreatitis occurred. Patient reported an improve life quality due to alleviated chronic abdominal pain and headaches.
CONCLUSIONS
Our case reports a rare yet potentially life-threatening condition-monogenic hypertriglyceridemia-induced acute pancreatitis. The implementation of the antisense drug volanesorsen resulted in improved triglyceride levels, alleviated symptoms, and enhanced the quality of life.
Topics: Humans; Male; Adult; Pancreatitis; Apolipoprotein A-V; Hypertriglyceridemia; Recurrence; Homozygote; Mutation; Oligonucleotides; Hyperlipoproteinemia Type I; Diet, Fat-Restricted; Triglycerides
PubMed: 38872171
DOI: 10.1186/s13256-024-04532-0 -
BMC Genomics Jun 2024The association between Apolipoprotein A5 (APOA5) genetic polymorphisms and susceptibility to metabolic syndrome (MetS) has been established by many studies, but there... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The association between Apolipoprotein A5 (APOA5) genetic polymorphisms and susceptibility to metabolic syndrome (MetS) has been established by many studies, but there have been conflicting results from the literature. We performed a meta-analysis of observational studies to evaluate the association between APOA5 gene polymorphisms and the prevalence of MetS.
METHODS
PubMed, Web of Science, Embase, and Scopus were searched up to April 2024. The random effects model was used to estimate the odds ratios (ORs) and 95% confidence intervals (CI) of the association between APOA5 gene polymorphisms and the prevalence of MetS development. The potential sources of heterogeneity were evaluated by subgroup analyses and sensitivity analyses.
RESULTS
A total of 30 studies with 54,986 subjects (25,341 MetS cases and 29,645 healthy controls) were included. The presence of rs662799 and rs651821 polymorphisms is associated with an approximately 1.5-fold higher likelihood of MetS prevalence (OR = 1.42, 95% CI: 1.32, 1.53, p < 0.001; I = 67.1%; P-heterogeneity < 0.001; and OR = 1.50, 95% CI: 1.36-1.65, p < 0.001), respectively. MetS is also more prevalent in individuals with the genetic variants rs3135506 and rs2075291. There was no evidence of a connection with rs126317.
CONCLUSION
The present findings suggest that polymorphisms located in the promoter and coding regions of the APOA5 gene are associated with an increased prevalence of MetS in the adult population. Identifying individuals with these genetic variations could lead to early disease detection and the implementation of preventive strategies to reduce the risk of MetS and its related health issues. However, because the sample size was small and there was evidence of significant heterogeneity for some APOA5 gene polymorphisms, these results need to be confirmed by more large-scale and well-designed studies.
Topics: Metabolic Syndrome; Apolipoprotein A-V; Humans; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Odds Ratio
PubMed: 38867151
DOI: 10.1186/s12864-024-10493-x -
Frontiers in Endocrinology 2024Observational studies suggest an association between telomere length (TL) and blood lipid (BL) levels. Nevertheless, the causal connections between these two traits...
BACKGROUND
Observational studies suggest an association between telomere length (TL) and blood lipid (BL) levels. Nevertheless, the causal connections between these two traits remain unclear. We aimed to elucidate whether genetically predicted TL is associated with BL levels via Mendelian randomization (MR) and vice versa.
METHODS
We obtained genetic instruments associated with TL, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-1 (ApoA-1) and apolipoprotein B (ApoB) from large-scale genome-wide association studies (GWASs). The causal relationships between TL and BL were investigated via bidirectional MR, multivariable MR and mediation analysis methods. The inverse variance weighted (IVW) method was employed as the principal methodology, complemented by several other estimators to enhance the robustness of the analysis.
RESULTS
In the forward MR analyses, we identified significant positive correlation between genetically predicted TL and the levels of TG (β=0.04, 95% confidence interval [CI]: 0.01 to 0.06, p = 0.003). In the reverse MR analysis, TG (β=0.02, 95% CI: 0.01 to 0.03, p = 0.004), LDL-C (β=0.03, 95% CI: 0.01 to 0.04, p = 0.001) and ApoB (β=0.03, 95% CI: 0.01 to 0.04, p = 9.71×10) were significantly positively associated with TL, although this relationship was not observed in the multivariate MR analysis. The mediation analysis via two-step MR showed no significant mediation effects acting through obesity-related phenotypes in analysis of TL with TG, while the effect of LDL-C on TL was partially mediated by body mass index (BMI) in the reverse direction, with mediated proportion of 12.83% (95% CI: 0.62% to 25.04%).
CONCLUSIONS
Our study indicated that longer TL were associated with higher TG levels, while conversely, higher TG, LDL-C, and ApoB levels predicted longer TL, with BMI partially mediating these effects. Our findings present valuable insights into the development of preventive strategies and interventions that specifically target TL-related aging and age-related diseases.
Topics: Humans; Mendelian Randomization Analysis; Genome-Wide Association Study; Lipids; Cholesterol, LDL; Triglycerides; Telomere; Cholesterol, HDL; Polymorphism, Single Nucleotide; Telomere Homeostasis; Apolipoprotein A-I
PubMed: 38863926
DOI: 10.3389/fendo.2024.1338698 -
Aging Jun 2024Although platinum-based chemotherapy is the frontline regimen for colorectal cancer (CRC), drug resistance remains a major challenge affecting its therapeutic...
Although platinum-based chemotherapy is the frontline regimen for colorectal cancer (CRC), drug resistance remains a major challenge affecting its therapeutic efficiency. However, there is limited research on the correlation between chemotherapy resistance and lipid metabolism, including PIK3CA mutant tumors. In this present study, we found that PIK3CA-E545K mutation attenuated cell apoptosis and increased the cell viability of CRC with L-OHP treatment and . Mechanistically, PIK3CA-E545K mutation promoted the nuclear accumulation of SREBP1, which promoted the transcription of Apolipoprotein A5 (APOA5). APOA5 activated the PPARγ signaling pathway to alleviate reactive oxygen species (ROS) production following L-OHP treatment, which contributed to cell survival of CRC cells. Moreover, APOA5 overexpression enhanced the stemness-related traits of CRC cells. Increased APOA5 expression was associated with PIK3CA mutation in tumor specimens and poor response to first-line chemotherapy, which was an independent detrimental factor for chemotherapy sensitivity in CRC patients. Taken together, this study indicated that PIK3CA-E545K mutation promoted L-OHP resistance by upregulating APOA5 transcription in CRC, which could be a potent target for improving L-OHP chemotherapeutic efficiency. Our study shed light to improve chemotherapy sensitivity through nutrient management in CRC.
Topics: Humans; Colorectal Neoplasms; Drug Resistance, Neoplasm; Apolipoprotein A-V; Oxaliplatin; Reactive Oxygen Species; Class I Phosphatidylinositol 3-Kinases; Mutation; Animals; Cell Line, Tumor; Antineoplastic Agents; Mice; Male; Apoptosis; Sterol Regulatory Element Binding Protein 1; Female; Gene Expression Regulation, Neoplastic; Signal Transduction
PubMed: 38848145
DOI: 10.18632/aging.205872 -
PLoS Computational Biology May 2024Lecithin:cholesterol acyltransferase (LCAT) exhibits α-activity on high-density and β-activity on low-density lipoproteins. However, the molecular determinants...
Systematic evaluation of lecithin:cholesterol acyltransferase binding sites in apolipoproteins via peptide based nanodiscs: regulatory role of charged residues at positions 4 and 7.
Lecithin:cholesterol acyltransferase (LCAT) exhibits α-activity on high-density and β-activity on low-density lipoproteins. However, the molecular determinants governing LCAT activation by different apolipoproteins remain elusive. Uncovering these determinants would offer the opportunity to design and explore advanced therapies against dyslipidemias. Here, we have conducted coarse-grained and all-atom molecular dynamics simulations of LCAT with nanodiscs made with α-helical amphiphilic peptides either derived from apolipoproteins A1 and E (apoA1 and apoE) or apoA1 mimetic peptide 22A that was optimized to activate LCAT. This study aims to explore what drives the binding of peptides to our previously identified interaction site in LCAT. We hypothesized that this approach could be used to screen for binding sites of LCAT in different apolipoproteins and would provide insights to differently localized LCAT activities. Our screening approach was able to discriminate apoA1 helixes 4, 6, and 7 as key contributors to the interaction with LCAT supporting the previous research data. The simulations provided detailed molecular determinants driving the interaction with LCAT: the formation of hydrogen bonds or salt bridges between peptides E4 or D4 and LCAT S236 or K238 residues. Additionally, salt bridging between R7 and D73 was observed, depending on the availability of R7. Expanding our investigation to diverse plasma proteins, we detected novel LCAT binding helixes in apoL1, apoB100, and serum amyloid A. Our findings suggest that the same binding determinants, involving E4 or D4 -S236 and R7-D73 interactions, influence LCAT β-activity on low-density lipoproteins, where apoE and or apoB100 are hypothesized to interact with LCAT.
Topics: Phosphatidylcholine-Sterol O-Acyltransferase; Binding Sites; Molecular Dynamics Simulation; Apolipoproteins; Apolipoprotein A-I; Humans; Peptides; Nanostructures; Protein Binding; Apolipoproteins E
PubMed: 38805510
DOI: 10.1371/journal.pcbi.1012137