Study on interaction with high-abundant blood proteins and identification of low-abundant proteins to 5-phenyl-1-(p-tolyl)-1 H-1,2,3-triazole by serum proteomics.

In this study, a comprehensive investigation was undertaken to elucidate a simple triazole compound, 5-phenyl-1-(p-tolyl)-1 H-1,2,3-triazole (PPTT), its interactions with high-abundant proteins and identification of low-abundant proteins by serum proteomics. Employing a combination of spectroscopic techniques and computational chemistry, the interactions between PPTT and three high-abundance blood globular proteins, namely human serum albumin (HSA), human immunoglobulin G (HIgG), and hemoglobin (BHb), were explored, thereby ascertaining their binding constants and thermodynamic parameters at the molecular level. Subsequently, based on the differential proteomics, utilizing two-dimensional gel electrophoresis (2-DE) in conjunction with matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF-MS), the research team isolated and identified differentially expressed low-abundance proteins in human blood serum samples following exposure to PPTT. The results showed that there were twenty highly expressed proteins identified from blood serum samples intervened by PPTT. Combining bioinformatics techniques, these proteins were classified, providing preliminary insights like preproprotein or precursors inhibiting the activity of elastase, defending and regulating the immune system, carrying lipid, and other functions into their biological functionalities. One of the differential proteins, apolipoprotein A-1 (ApoA-1) protein, was selected as a possible target to explore the mechanism of action of PPTT intervention on the related signaling pathways involved in human hepatocellular carcinomas(Hep G2) cells. These research findings offer scientifically sound guidance for further in-depth exploration, development, and application of the 1,2,3-triazole compound.

Differences in HDL Remodeling during Healthy Pregnancy and Pregnancy with Cardiometabolic Complications.

This study investigated the longitudinal trajectory of changes in antioxidative and anti-inflammatory high-density lipoprotein (HDL) components during healthy pregnancy and pregnancy with cardiometabolic complications. We recruited and longitudinally followed 84 women with healthy pregnancies and 46 pregnant women who developed cardiometabolic pregnancy complications (gestational diabetes mellitus and hypertensive disorders of pregnancy). Their general lipid profiles, oxidative stress status, inflammatory status, and antioxidative and anti-inflammatory HDL components were analyzed. The results of our study confirmed the expected trajectory for the routine lipid parameters. Our study results indicate more intensive oxidative stress and a higher level of inflammation in the group with complications compared with the control group. Sphingosine-1-phosphate (S1P) was significantly lower in the first trimester in the group with complications compared with the control group (p < 0.05). We did not find significant differences in the apolipoprotein A1 (Apo A1) concentrations in the first trimester between the control group and the group with complications, but in the second and third trimesters, the group with complications had significantly higher concentrations (p < 0.001, p < 0.05, respectively). The S1P, paraoxonase 1 (PON1), and serum amyloid A (SAA) concentrations were significantly lower in the group with complications in the first trimester. During the second trimester, only the SAA concentrations were identified as significantly lower in the group with complications compared with the control group, while in the third trimester, the PON1, apolipoprotein M (Apo M), and SAA concentrations were all significantly lower in the group with complications. Through a multivariate binary logistic regression analysis, the S1P concentration in the first trimester was distinguished as an HDL-associated marker independently associated with cardiometabolic pregnancy complications. In conclusion, our study results showed that HDL remodeling differs between healthy pregnancies and pregnancies with maternal cardiometabolic complications, with changed HDL composition and functionality consequently impacting its biological functionality in the latter case.

Association of apolipoprotein A1 levels with lumbar bone mineral density and ß-CTX in osteoporotic fracture individuals: a cross-sectional investigation.

Background: The relationship between the levels of high-density lipoprotein (HDL) and bone mineral density (BMD) is controversial. Furthermore, the specific role of apolipoprotein A1 (APOA1), a primary HDL component, in regulating BMD remains unclear. This study aimed to elucidate the correlation between APOA1 levels and lumbar BMD in patients with osteoporotic fracture (OPF) for novel insights into potential therapeutic strategies against osteoporosis. Methods: This study included 587 OPF patients enrolled at the Kunshan Hospital, Affiliated with Jiangsu University between January 2017 and July 2022. The patient's serum APOA1 levels were determined, followed by the assessment of lumbar BMD and C-terminal telopeptide of type I collagen (ß-CTX) as outcome variables. The association of APOA1 levels with lumbar BMD and ß-CTX was assessed via Generalized Estimating Equations (GEE) and spline smoothing plot analyses. A generalized additive model (GAM) helped ascertain non-linear correlations. Moreover, a subgroup analysis was also conducted to validate the result's stability. Results: It was observed that APOA1 levels were positively correlated with lumbar BMD (ß = 0.07, 95% CI: 0.02 to 0.11, p = 0.0045), indicating that increased APOA1 levels were linked with enhanced lumbar BMD. Furthermore, APOA1 levels were negatively related to ß-CTX (ß = -0.19, 95% CI: -0.29 to -0.09, p = 0.0003), suggesting APOA1 might reduce osteolysis. In addition, these findings were robustly supported by subgroup and threshold effect analyses. Conclusion: This study indicated that increased APOA1 levels were correlated with enhanced lumbar BMD and decreased osteolysis in OPF patients. Therefore, APOA1 may inhibit osteoclast activity to prevent further deterioration in osteoporotic patients. However, further research I warranted to validate these conclusions and elucidate the underlying physiologies.

Obesity and adiposity promote the development of non-suppurative otitis media: a Mendelian randomization study.

Background: Observational studies have found that obesity is associated with the development of non-suppurative otitis media (NSOM), but the causality and pathogenesis are unclear. This study aimed to investigate the association between obesity, lipid metabolism, and NSOM at the genetic level. Methods: We performed a bidirectional two-sample Mendelian randomization (MR) study to examine the causal relationship between obesity, lipid metabolism-related factors, and NSOM by using the datasets obtained from the IEU Open genome-wide association studies (GWAS) Project. Furthermore, a multivariate MR (MVMR) analysis on lipid indicators was conducted to validate the results. We then used obesity or body mass index (BMI) as the exposure and NSOM as the outcome to search for possible mediators in lipids and adipokines. Results: Using NSOM as the outcome, we found nine positive exposure results related to obesity and lipid metabolism. Among them, obesity, BMI, body fat percentage, waist circumference, hip circumference, and resistin were risk factors, while apolipoprotein A1 (apoA1), high-density lipoprotein cholesterol (HDL-C), and nerve growth factor (NGF) were protective factors. Then, we used the obesity and lipid metabolism-related factors as outcomes and NSOM as the exposure to perform the MR analysis, which failed to obtain positive results. In the MVMR analysis, we found that HDL cholesterol and apoA1 remained causally associated with NSOM after correction for other potential confounders. Simultaneously, when obesity or BMI was used as the exposure and NSOM as the outcome, HDL cholesterol or apoA1 served as mediators through a two-step MR analysis. The MR analysis for mediation, obesity, and BMI reduced the production of HDL or apoA1, which served as protective factors affecting the development of NSOM. Conclusion: At the genetic level, obesity and adiposity may promote the development of NSOM, while NSOM has no effect on obesity and adiposity. Obesity can also encourage the progress of NSOM by reducing HDL cholesterol/apoA1. Resistin may be a potential risk factor for NSOM, whereas NGF may be a potential protective factor.

Anti-apolipoprotein A-1 IgG, incident cardiovascular events, and lipid paradox in rheumatoid arthritis.

Objective: To validate the prognostic accuracy of anti-apolipoprotein A-1 (AAA1) IgG for incident major adverse cardiovascular (CV) events (MACE) in rheumatoid arthritis (RA) and study their associations with the lipid paradox at a multicentric scale. Method: Baseline AAA1 IgG, lipid profile, atherogenic indexes, and cardiac biomarkers were measured on the serum of 1,472 patients with RA included in the prospective Swiss Clinical Quality Management registry with a median follow-up duration of 4.4 years. MACE was the primary endpoint defined as CV death, incident fatal or non-fatal stroke, or myocardial infarction (MI), while elective coronary revascularization (ECR) was the secondary endpoint. Discriminant accuracy and incidence rate ratios (IRR) were respectively assessed using C-statistics and Poisson regression models. Results: During follow-up, 2.4% (35/1,472) of patients had a MACE, consisting of 6 CV deaths, 11 MIs, and 18 strokes; ECR occurred in 2.1% (31/1,472) of patients. C-statistics indicated that AAA1 had a significant discriminant accuracy for incident MACE [C-statistics: 0.60, 95% confidence interval (95% CI): 0.57-0.98, p = 0.03], mostly driven by CV deaths (C-statistics: 0.77; 95% CI: 0.57-0.98, p = 0.01). IRR indicated that each unit of AAA1 IgG increase was associated with a fivefold incident CV death rate, independent of models' adjustments. At the predefined and validated cut-off, AAA1 displayed negative predictive values above 97% for MACE. AAA1 inversely correlated with total and HDL cholesterol. Conclusions: AAA1 independently predicts CV deaths, and marginally MACE in RA. Further investigations are requested to ascertain whether AAA1 could enhance CV risk stratification by identifying patients with RA at low CV risk.

High Apolipoprotein B/Apolipoprotein A1 is Associated with Vitamin D Deficiency Among Type 2 Diabetes Patients.

Purpose: To explore the relationship between vitamin D (VitD) deficiency and the apolipoprotein B/apolipoprotein A1 (apo B/A1) in type 2 diabetes mellitus (T2DM) patients. Methods: This was a retrospective study that lasted 2 years and 6 months, collecting information and laboratory data from 784 patients with T2DM. Patients were divided into VitD deficiency group (n = 433) and non-VitD deficiency group (n = 351) based on VitD levels. Calculated apo B/A1 ratio, and patients were further divided into high-apo B/A1 group (n = 392) and low-apo B/A1 group (n = 392) based on the median of the apo B/A1. All data were analyzed using Prism 8.0.1 and R version 4.3.1 software. Results: Apo B/A1 levels of T2DM patients combined with VitD deficiency was significantly higher than that of non-VitD deficiency patients, and the VitD levels of patients with high apo B/A1 was significantly lower than that patients with low apo B/A1 (all P<0.001). Spearman correlation analysis showed that VitD levels were negatively correlated with apo B/A1 (r=-0.238, P<0.001). Multiple linear regression analysis revealed after adjusting other factors, VitD levels were significantly negatively associated with apo B/A1 (ß=-0.123, P=0.001). Binary logistic regression analysis showed apoB/A1 was an independent risk factor for VitD deficiency in T2DM patients. Restrictive cubic spline indicated a significant linear relationship between apoB/A1 and VitD deficiency (P general trend <0.0001, P nonlinear = 0.0896), after stratification of gender, the results showed that apo B/A1 was more susceptible to VitD deficiency in female patients. The receiver operating characteristic (ROC) curve analysis showed that the area under the curve, sensitivity and specificity of the apo B/A1 for VitD deficiency were 0.654, 66.3% and 59.8%, respectively. Conclusion: The apo B/A1 was significantly negatively associated with VitD levels and an independent risk factor for VitD deficiency in patients with T2DM.

Relationships Between the Apolipoprotein Levels and Sarcopenia in Inpatients with Type 2 Diabetes Mellitus: A Cross-Sectional Study.

Background: Apolipoprotein (Apo) may be associated with sarcopenia in elderly inpatients with type 2 diabetes mellitus (T2DM), but fewer studies are available. In this study, we explored the association of ApoA1, ApoB, and ApoB/ApoA1 with sarcopenia and compared the predictive role of Apo indicators for sarcopenia in an elderly T2DM. Objective: To investigate the relationships between the Apo and sarcopenia in elderly inpatients with T2DM. Methods: This study included 253 inpatients with T2DM (mean age of 70.11±5.44 years, 32.8% male). The inpatients were divided into the sarcopenic group (n = 100) and non-sarcopenic group (n = 153). The associations among the Apo and sarcopenia were assessed using multivariate analyses. Results: Inpatients in the sarcopenia group showed lower ApoA1 levels than those in the non-sarcopenia group (1.25±0.21 vs 1.36±0.20 g/L, P < 0.05) and showed higher ApoB/ApoA1 and ApoB levels than those in the non-sarcopenia group (0.82±0.27 vs 0.69±0.19 g/L, P < 0.05;1.00±0.32 vs 0.93±0.24 g/L, P < 0.05, respectively). After adjusting for age and BMI, the logistic regression model indicated that ApoA1 was a protective factor for elderly inpatients with T2DM sarcopenia.(OR =0.079,95% CI: 0.021~0.306, P < 0.05);ApoB and AopB/AopA1 were risk factors for elderly inpatients with T2DM sarcopenia.(OR =3.578,95% CI:1.318~9.715, P < 0.05;OR =16.440,95% CI:4.437~60.427, P < 0.05, respectively). AopB/AopA1 provided an AUC value of 0.765 in elderly men.(95% CI: 0.665~0.866, P<0.05). Conclusion: ApoA1, AopB, and AopB/AopA1 are associated with sarcopenia in elderly inpatients with T2DM, and AopB/AopA1 may be a potential predictor of sarcopenia in elderly men with T2DM.

Association of High apoB/apoA1 Ratio with Increased Erythrocytes, Platelet/Lymphocyte Ratio, D-dimer, Uric Acid and Cardiac Remodeling in Elderly Heart Failure Patients: A Retrospective Study.

Background: Previous studies have confirmed that high apolipoprotein B/apolipoprotein A1 (apoB/apoA1) ratio was associated with increased mortality from heart failure (HF). Furthermore, the association of plasma apoB/apoA1 ratio with clinical characteristics and adverse cardiac remodeling is still limited in chronic HF with mildly reduced ejection fraction (HFmrEF) elderly patients. Therefore, this study investigated the association of apoB/apoA1 ratio with clinical characteristics and adverse cardiac remodeling in chronic HFmrEF elderly patients. Methods: A total of 587 Chinese elderly (≥65 years) with coronary heart disease (CHD), HFmrEF (EF 40-50%) and related blood biochemical data were collected retrospectively. The cross-sectional data of echocardiographic and blood parameters were compared between binary apoB/apoA1 groups. Results: In the elderly CHD patients with chronic HFmrEF, the univariate correlation analysis showed that apoB/apoA1 was correlated with younger age, increased prevalence of type 2 diabetes, erythrocytes, platelet/lymphocyte ratio (PLR), D-dimer, fibrinogen, high sensitivity C-reactive protein and uric acid, and adverse cardiac remodeling (All P < 0.05). However, multivariate logistic binary regression analysis found that high apoB/apoA1 ratio (≥0.62) was independently correlated with younger age, increased erythrocytes, PLR, D-dimer and uric acid, and adverse cardiac remodeling (All P < 0.05). Conclusion: In this retrospective study, the high apoB/apoA1 ratio is found to be associated with younger age, increased erythrocytes, PLR, D-dimer and uric acid, and adverse cardiac remodeling in Chinese CHD elderly with chronic HFmrEF.

The neutrophil-to-apolipoprotein A1 ratio is associated with adverse outcomes in patients with acute decompensated heart failure at different glucose metabolic states: a retrospective cohort study.

BACKGROUND: The present study was performed to assess the association between the neutrophil-to-apolipoprotein A1 ratio (NAR) and outcomes in patients with acute decompensated heart failure (ADHF) at different glucose metabolism states. METHODS: We recruited 1233 patients with ADHF who were admitted to Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University from December 2014 to October 2019. The endpoints were defined as composites of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke and exacerbation of chronic heart failure. The restricted cubic spline was used to determine the best cutoff of NAR, and patients were divided into low and high NAR groups. Kaplan-Meier plots and multivariable Cox proportional hazard models were used to investigate the association between NAR and the risk of adverse outcomes. RESULTS: During the five-year follow-up period, the composite outcome occurred in 692 participants (56.1%). After adjusting for potential confounding factors, a higher NAR was associated with a higher incidence of composite outcomes in the total cohort (Model 1: HR = 1.42, 95% CI = 1.22-1.65, P<0.001; Model 2: HR = 1.29, 95% CI = 1.10-1.51, P = 0.002; Model 3: HR = 1.20, 95% CI = 1.01-1.42, P = 0.036). At different glucose metabolic states, a high NAR was associated with a high risk of composite outcomes in patients with diabetes mellitus (DM) (Model 1: HR = 1.54, 95% CI = 1.25-1.90, P<0.001; Model 2: HR = 1.40, 95% CI = 1.13-1.74, P = 0.002; Model 3: HR = 1.31, 95% CI = 1.04-1.66, P = 0.022), and the above association was not found in patients with prediabetes mellitus (Pre-DM) or normal glucose regulation (NGR) (both P>0.05). CONCLUSIONS: The NAR has predictive value for adverse outcomes of ADHF with DM, which implies that the NAR could be a potential indicator for the management of ADHF.

Oncolytic adenovirus encoding apolipoprotein A1 suppresses metastasis of triple-negative breast cancer in mice.

BACKGROUND: Dysregulation of cholesterol metabolism is associated with the metastasis of triple-negative breast cancer (TNBC). Apolipoprotein A1 (ApoA1) is widely recognized for its pivotal role in regulating cholesterol efflux and maintaining cellular cholesterol homeostasis. However, further exploration is needed to determine whether it inhibits TNBC metastasis by affecting cholesterol metabolism. Additionally, it is necessary to investigate whether ApoA1-based oncolytic virus therapy can be used to treat TNBC. METHODS: In vitro experiments and mouse breast cancer models were utilized to evaluate the molecular mechanism of ApoA1 in regulating cholesterol efflux and inhibiting breast cancer progression and metastasis. The gene encoding ApoA1 was inserted into the adenovirus genome to construct a recombinant adenovirus (ADV-ApoA1). Subsequently, the efficacy of ADV-ApoA1 in inhibiting the growth and metastasis of TNBC was evaluated in several mouse models, including orthotopic breast cancer, spontaneous breast cancer, and human xenografts. In addition, a comprehensive safety assessment of Syrian hamsters and rhesus monkeys injected with oncolytic adenovirus was conducted. RESULTS: This study found that dysregulation of cholesterol homeostasis is critical for the progression and metastasis of TNBC. In a mouse orthotopic model of TNBC, a high-cholesterol diet promoted lung and liver metastasis, which was associated with keratin 14 (KRT14), a protein responsible for TNBC metastasis. Furthermore, studies have shown that ApoA1, a cholesterol reverse transporter, inhibits TNBC metastasis by regulating the cholesterol/IKBKB/FOXO3a/KRT14 axis. Moreover, ADV-ApoA1 was found to promote cholesterol efflux, inhibit tumor growth, reduce lung metastasis, and prolonged the survival of mice with TNBC. Importantly, high doses of ADV-ApoA1 administered intravenously and subcutaneously were well tolerated in rhesus monkeys and Syrian hamsters. CONCLUSIONS: This study provides a promising oncolytic virus treatment strategy for TNBC based on targeting dysregulated cholesterol metabolism. It also establishes a basis for subsequent clinical trials of ADV-ApoA1 in the treatment of TNBC.

Apolipoprotein A1 and high-density lipoprotein limit low-density lipoprotein transcytosis by binding SR-B1.

Atherosclerosis results from the deposition and oxidation of LDL and immune cell infiltration in the sub-arterial space leading to arterial occlusion. Studies have shown that transcytosis transports circulating LDL across endothelial cells lining blood vessels. LDL transcytosis is initiated by binding to either scavenger receptor B1 (SR-B1) or activin A receptor-like kinase 1 on the apical side of endothelial cells leading to its transit and release on the basolateral side. HDL is thought to partly protect individuals from atherosclerosis due to its ability to remove excess cholesterol and act as an antioxidant. Apolipoprotein A1 (APOA1), an HDL constituent, can bind to SR-B1, raising the possibility that APOA1/HDL can compete with LDL for SR-B1 binding, thereby limiting LDL deposition in the sub-arterial space. To examine this possibility, we used in vitro approaches to quantify the internalization and transcytosis of fluorescent LDL in coronary endothelial cells. Using microscale thermophoresis and affinity capture, we find that SR-B1 and APOA1 interact and that binding is enhanced when using the cardioprotective variant of APOA1 termed Milano (APOA1-Milano). In male mice, transiently increasing the levels of HDL reduced the acute deposition of fluorescently labeled LDL in the atheroprone inner curvature of the aorta. Reduced LDL deposition was also observed when increasing circulating wild-type APOA1 or the APOA1-Milano variant, with a more robust inhibition from the APOA1-Milano. The results suggest that HDL may limit SR-B1-mediated LDL transcytosis and deposition, adding to the mechanisms by which it can act as an atheroprotective particle.

Increased Apolipoprotein A1 Expression Correlates with Tumor-Associated Neutrophils and T Lymphocytes in Upper Tract Urothelial Carcinoma.

An increased neutrophil-to-lymphocyte ratio (NLR) is a poor prognostic biomarker in various types of cancer, because it reflects the inhibition of lymphocytes in the circulation and tumors. In urologic cancers, upper tract urothelial carcinoma (UTUC) is known for its aggressive features and lack of T cell infiltration; however, the association between neutrophils and suppressed T lymphocytes in UTUC is largely unknown. In this study, we examined the relationship between UTUC-derived factors and tumor-associated neutrophils or T lymphocytes. The culture supernatant from UTUC tumor tissue modulated neutrophils to inhibit T cell proliferation. Among the dominant factors secreted by UTUC tumor tissue, apolipoprotein A1 (Apo-A1) exhibited a positive correlation with NLR. Moreover, tumor-infiltrating neutrophils were inversely correlated with tumor-infiltrating T cells. Elevated Apo-A1 levels in UTUC were also inversely associated with the population of tumor-infiltrating T cells. Our findings indicate that elevated Apo-A1 expression in UTUC correlates with tumor-associated neutrophils and T cells. This suggests a potential immunomodulatory effect on neutrophils and T cells within the tumor microenvironment, which may represent therapeutic targets for UTUC treatment.

Predictive value of neutrophil to apolipoprotein A1 ratio in patients with acute ischaemic stroke.

The neutrophil to apolipoprotein A1 ratio has emerged as a possible prognostic biomarker in different medical conditions. Nonetheless, the predictive potential of neutrophil to apolipoprotein A1 ratio in determining the 3-month prognosis of acute ischaemic stroke patients who undergo intravenous thrombolysis has yet to be fully acknowledged. In this study, 196 acute ischaemic stroke patients with recombinant tissue plasminogen activator and 133 healthy controls were included. Meanwhile, we incorporated a total of 386 non-thrombolytic acute ischaemic stroke patients. The acute ischaemic stroke patients with recombinant tissue plasminogen activator were divided into four groups based on quartiles of neutrophil to apolipoprotein A1 ratio. The association between neutrophil to apolipoprotein A1 ratio and the 3-month prognosis was evaluated through univariate and multivariate regression analyses. Additionally, subgroup analyses were conducted to investigate the predictive value of neutrophil to apolipoprotein A1 ratio in different patient populations. Adverse outcomes were defined as a modified Rankin Scale score of 3-6. The study findings revealed a significant association between elevated neutrophil to apolipoprotein A1 ratio levels and poor prognosis in acute ischaemic stroke patients. In the highest quartile of neutrophil to apolipoprotein A1 ratio levels (Q4), after controlling for age, gender, admission National Institutes of Health Stroke Scale score, blood urea nitrogen and stroke subtypes, the odds ratio for adverse outcomes at 3 months was 13.314 (95% confidence interval: 2.878-61.596, P = 0.001). An elevated neutrophil to apolipoprotein A1 ratio value was found to be associated with a poor prognosis in acute ischaemic stroke patients, regardless of whether they received recombinant tissue plasminogen activator treatment or not. The new model, which incorporating neutrophil to apolipoprotein A1 ratio into the conventional model, demonstrated a statistically significant improvement in discriminatory power and risk reclassification for 3-month poor outcomes in acute ischaemic stroke patients treated with recombinant tissue plasminogen activator. The new model exhibited a categorical net reclassification index (P = 0.035) of 12.9% and an integrated discrimination improvement (P = 0.013) of 5.2%. Subgroup analyses indicated that the predictive value of neutrophil to apolipoprotein A1 ratio differed across stroke subtypes. Neutrophil to apolipoprotein A1 ratio is a potential biomarker for predicting the prognosis of acute ischaemic stroke patients. The clinical implications of our findings are significant, as early identification and intervention in high-risk patients can improve their outcomes. However, further studies are required to validate our results and elucidate the underlying mechanisms of the association between neutrophil to apolipoprotein A1 ratio and poor prognosis in acute ischaemic stroke patients.

[－75 G/A Polymorphism of Apolipoprotein A1 Gene Promoter Region in Normal Pregnant Women and Patients With Gestational Diabetes Mellitus]. / æ­£å¸¸å­•å¦‡åŠå¦Šå¨ ç³–å°¿ç— æ‚£è€ apoA1åŸºå› å¯åŠ¨å­åŒºï¼75 G/Aå¤šæ€æ€§çš„ç ”ç©¶.

Objective: To investigate the －75 G/A single-nucleotide polymorphism in the promoter region of apolipoprotein A1 gene (apoA1) and its association with gestational diabetes mellitus (GDM) in pregnant women and to provide references for the exploration in the molecular genetic basis of GDM. Methods: A total of 626 GDM patients and 1022 normal pregnant women, ie, the controls, were included in the study. The genotyping of apoA1 －75 G/A polymorphism was performed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and glucose (Glu) were measured by enzymatic methods. Plasma insulin (INS) was measured by chemiluminescence immunoassay. The protein levels of apoA1 and apoB were measured by the turbidimetric immunoassay. Results: Allele frequencies of G and A were 0.718 and 0.282 in the GDM group and 0.713 and 0.287 in the control group, respectively. Distribution of the genotype frequencies was found to be in Hardy-Weinberg equilibrium in both the GDM and control groups. There was no significant difference in the frequencies of alleles G and A and the genotypes of apoA1 －75 G/A polymorphism between the GDM and the control group (P>0.05). In the GDM group, the carriers with the genotype AA were associated with significantly higher levels of TC, HDL-C, and apoA1 than those with genotypes GG and GA did (all P<0.05). After the GDM patients were divided into obese and non-obese subgroups, the genotype-related apoA1 variation was observed only in obese patients, while the genotype-related TC and HDL-C variations were evident in non-obese patients (P<0.05). In the control group, carriers of genotypes AA and GA had higher systolic blood pressure (SBP) and HDL-C than the carriers of genotype GG did (all P<0.05). Carriers of genotypes AA had significantly lower Glu levels than carriers of genotypes GG and GA did (P<0.05). The control subjects were further divided into subgroups according to their body mass index (BMI). Analysis of the subgroups showed that AA carriers were associated with higher SBP levels in the obese control women only, while lower Glu levels were evident in both obese and non-obese control women. Conclusion: These results suggest that －75 G/A polymorphism in the apoA1 gene is not associated with GDM. However, the genetic variation is closed associated with the plasma apoA1, HDL-C, and TC levels in GDM patients and plasma HDL-C, Glu, and SBP levels in the control subjects. The apoA1 variant-associated lipids and SBP variation is BMI dependent in both groups.

People living with HIV display increased anti-apolipoprotein A1 auto-antibodies, inflammation, and kynurenine metabolites: a case-control study.

Objective: This study aimed to study the relationship between auto-antibodies against apolipoprotein A1 (anti-apoA1 IgG), human immunodeficiency virus (HIV) infection, anti-retroviral therapy (ART), and the tryptophan pathways in HIV-related cardiovascular disease. Design: This case-control study conducted in South Africa consisted of control volunteers (n = 50), people living with HIV (PLWH) on ART (n = 50), and untreated PLWH (n = 44). Cardiovascular risk scores were determined, vascular measures were performed, and an extensive biochemical characterisation (routine, metabolomic, and inflammatory systemic profiles) was performed. Methods: Anti-apoA1 IgG levels were assessed by an in-house ELISA. Inflammatory biomarkers were measured with the Meso Scale Discovery® platform, and kynurenine pathway metabolites were assessed using targeted metabolomic profiling conducted by liquid chromatography-multiple reaction monitoring/mass spectrometry (LC-MRM/MS). Results: Cardiovascular risk scores and vascular measures exhibited similarities across the three groups, while important differences were observed in systemic inflammatory and tryptophan pathways. Anti-apoA1 IgG seropositivity rates were 15%, 40%, and 70% in control volunteers, PLWH ART-treated, and PLWH ART-naïve, respectively. Circulating anti-apoA1 IgG levels were significantly negatively associated with CD4+ cell counts and positively associated with viremia and pro-inflammatory biomarkers (IFNγ, TNFα, MIPα, ICAM-1, VCAM-1). While circulating anti-apoA1 IgG levels were associated with increased levels of kynurenine in both control volunteers and PLWH, the kynurenine/tryptophan ratio was significantly increased in PLWH ART-treated. Conclusion: HIV infection increases the humoral response against apoA1, which is associated with established HIV severity criteria and kynurenine pathway activation.

Serum apolipoproteins and mortality risk: evidence from observational and Mendelian randomization analyses.

BACKGROUND: Apolipoproteins (APOs) have emerged as significant players in lipid metabolism that affects the risk of chronic disease. However, the impact of circulating APO concentrations on premature death remains undetermined. OBJECTIVES: This study aimed to investigate the associations of serum APOs with all-cause, cardiovascular disease (CVD)-related, and cancer-related mortality. METHODS: We included 340,737 participants who had serum APO measurements from the UK Biobank. Restricted cubic splines and multivariable Cox regression models were used to assess the associations between APOs and all-cause and cause-specific mortality by computing hazard ratios (HRs) and 95% confidence intervals (CIs). Based on 1-sample Mendelian randomization (MR) design, including 398,457 participants of White ancestry who had genotyping data from the UK Biobank, we performed instrumental variable analysis with 2-stage least squares regression to assess the association between genetically predicted APOs and mortality. RESULTS: After adjusting for potential confounders including high-density and low-density lipoprotein particles, we observed nonlinear inverse relationships of APOA1 with all-cause, CVD-related, and cancer-related mortality (P-nonlinear < 0.001). By contrast, positive relationships were observed for APOB and all-cause (P-nonlinear < 0.001), CVD-related (P-linear < 0.001), and cancer-related (P-linear = 0.03) mortality. MR analysis showed consistent results, except that the association between APOB and cancer mortality was null. Furthermore, both observational and MR analyses found an inverse association between APOA1 and lung cancer-related mortality (HR comparing extreme deciles: 0.46; 95% CI: 0.26, 0.80; and HR: 0.78; 95% CI: 0.63, 0.97, respectively). CONCLUSIONS: Our findings indicate that circulating APOA1 has potential beneficial effects on all-cause, CVD-related, and lung cancer-related death risk, whereas APOB may confer detrimental effects on all-cause and CVD-related death risk.

Low serum apolipoprotein A1 level predicts poor prognosis of patients with diffuse large B-cell lymphoma in the real world: a retrospective study.

BACKGROUND: Apolipoprotein A1 (ApoA1) is a member of the apolipoprotein family with diverse functions. It is associated with the pathogenesis and prognosis of several types of tumors. However, the role of serum apolipoprotein A1 (ApoA1) in the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) remains unclear. This study aimed to elucidate its influence on clinical outcomes in patients with DLBCL. METHODS: We retrospectively analyzed a cohort of 1583 consecutive DLBCL patients admitted to the Fujian Medical University Union Hospital between January 2011 and December 2021. 949 newly diagnosed DLBCL patients who met the inclusion criteria were enrolled for statistical analysis. Receiver operating characteristic curve analysis was performed to determine the optimal cut-off value for serum ApoA1 levels for prognostic prediction among patients with DLBCL. The correlations between serum ApoA1 levels and clinical and laboratory parameters were analyzed. Prognostic significance was analyzed using univariate and multivariate Cox proportional hazards models. RESULTS: Newly diagnosed patients with DLBCL demonstrated low serum ApoA1 levels (< 0.925 g/L), had more B symptoms, higher levels of serum lactate dehydrogenase (LDH) (>upper limit of normal), poorer performance status (Eastern Cooperative Oncology Group score of 2-4), higher percentage of advanced stage and non-germinal center B-cell (non-GCB) subtype, more cases of > 1 extranodal site, higher International Prognostic Index (IPI) score (3-5), and higher incidence of relapse or refractory diseases compared with those with high serum ApoA1 levels (≥ 0.925 g/L). Low serum ApoA1 levels were an independent adverse prognostic factor for overall survival (OS) but not progression-free survival (PFS). CONCLUSIONS: Low serum ApoA1 levels were associated with poor treatment response and inferior survival in newly diagnosed patients with DLBCL.

Prognostic role of apolipoproteins on long-term major adverse cardiac events after percutaneous coronary intervention.

BACKGROUND/PURPOSE: Apolipoprotein (apo) levels are associated with coronary risk. However, the relationship between apo levels after percutaneous coronary intervention (PCI) and long-term major adverse cardiac events (MACEs) remains unclear. We aimed to investigate the association between lipid levels, including apo, at follow-up, and long-term MACEs in patients undergoing PCI. METHODS/MATERIALS: In total, 241 patients who underwent PCI between January 2004 and August 2008 were included in this study. MACEs were defined as cardiac death, acute coronary syndrome, or coronary revascularization of new lesions. The primary endpoint was MACE, and the secondary endpoint was a composite of cardiac death and acute coronary syndrome. RESULTS: During a mean follow-up period of 2079 days, the following cardiovascular events occurred in 78 patients: cardiovascular death (n = 1), non-fatal acute myocardial infarctions (n = 10), and revascularizations of new lesions (n = 67). Multivariate cox's proportional hazards analysis showed that the apo B level was an independent risk factor for MACEs (hazard ratio 1.11, 95 % confidence interval 1.03-1.20; P = 0.009). In the Kaplan-Meier estimation for primary endpoints, significant differences were observed in the apo B level and apo B/apo A1 ratio (P = 0.04 and P = 0.004, respectively). However, there was no difference in the LDL-C level and LDL-C/HDL-C ratio. At the secondary endpoint, only the apo B/apo A1 ratio was a prognostic factor (P = 0.007). CONCLUSIONS: In the long-term cardiovascular events of patients undergoing PCI, the apo B level and apo B/apo A1 ratio were more valuable prognostic factors for cardiovascular events compared to the LDL-C level and LDL-C/HDL-C ratio.

A new risk factor for coronary artery disease can be detected by an ApoA1 mAb-based assay.

BACKGROUND: This study aimed to find coronary artery disease (CAD) related apolipoprotein A1 (ApoA1) monoclonal antibody (mAb) and to evaluate the diagnostic value of the assay based on it. METHODS: Patients with CAD diagnosed by coronary angiography (disease group, n = 180) and healthy subjects (control group, n = 199) were recruited. The correlation between methods and CAD were evaluated by Spearman's rank correlation coefficients. Receiver operating characteristic (ROC) curve analysis was used to evaluate the auxiliary diagnostic value of methods for CAD. Odds ratios (ORs) of the test results in CAD were estimated using logistic regression analysis. RESULTS: Measurements from an ApoA1 mAb were found significantly positively correlated with CAD (r = 0.243, P < 0.01), unlike the measurements from the ApoA1 pAb were negatively correlated with CAD (r = -0.341, P < 0.001). The areas under the ROC curve of the ApoA1 mAb and pAb measurements were 0.704 and 0.563, respectively, in patients with normal HDL-C levels. ApoA1 values from the mAb assay had a significant positive impact on CAD risk. CONCLUSION: An ApoA1 mAb-based assay can distinguish a high-density lipoprotein (HDL) subclass positively related to CAD, which can be used to improve and reappraise CAD risk assessment.