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Current Issues in Molecular Biology Jun 2024Autoantibodies against apolipoprotein A-I (ApoA-I) are associated with cardiovascular disease risks. We aimed to examine the 4-hydroxy-2-nonenal (HNE) modification of...
Low Levels of IgM Recognizing 4-Hydroxy-2-Nonenal-Modified Apolipoprotein A-I Peptide and Its Association with the Severity of Coronary Artery Disease in Taiwanese Patients.
Autoantibodies against apolipoprotein A-I (ApoA-I) are associated with cardiovascular disease risks. We aimed to examine the 4-hydroxy-2-nonenal (HNE) modification of ApoA-I in coronary artery disease (CAD) and evaluate the potential risk of autoantibodies against their unmodified and HNE-modified peptides. We assessed plasma levels of ApoA-I, HNE-protein adducts, and autoantibodies against unmodified and HNE-peptide adducts, and significant correlations and odds ratios (ORs) were examined. Two novel CAD-specific HNE-peptide adducts, ApoA-I and ApoA-I, were identified. Notably, immunoglobulin G (IgG) anti-ApoA-I HNE, IgM anti-ApoA-I HNE, IgG anti-ApoA-I, IgG anti-ApoA-I, and HNE-protein adducts were significantly correlated with triglycerides, creatinine, or high-density lipoprotein in CAD with various degrees of stenosis (<30% or >70%). The HNE-protein adduct (OR = 2.208-fold, = 0.020) and IgM anti-ApoA-I HNE (2.046-fold, = 0.035) showed an increased risk of progression from >30% stenosis in CAD. HNE-protein adducts and IgM anti-ApoA-I HNE may increase the severity of CAD at high and low levels, respectively.
PubMed: 38921045
DOI: 10.3390/cimb46060374 -
Clinical and Translational... Jun 2024Dyslipidemia is one of the main risk factors for chronic metabolic diseases. Our previous studies have shown that washed microbiota transplantation (WMT) has a...
BACKGROUND AND AIMS
Dyslipidemia is one of the main risk factors for chronic metabolic diseases. Our previous studies have shown that washed microbiota transplantation (WMT) has a significant improvement effect on patients with hyperlipidemia and hypolipemia in the Chinese population. The purpose of this study is to further explore the long-term efficacy and safety of WMT in patients with hyperlipidemia.
METHODS
Clinical data of patients who received WMT for multi-course were collected. Changes of blood lipid indexes before and after WMT, including triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), lipoprotein a (LIP) and Apolipoprotein B (ApoB).
RESULTS
A total of 124 patients were enrolled, including 56 cases in hyperlipidemia group and 68 cases with normal lipids. The mean observation time was 787.80 ± 371.45 days, and the longest follow-up time was 1534 days. TC and non-HDL-C in hyperlipidemia group with 1 to 4 courses of WMT were significantly reduced (p < 0.05); TG decreased significantly after the second course (p < 0.05); LDL-C also significantly decreased after the fourth course of treatment (p < 0.05); TG, TC and non-HDL-C significantly decreased in single-course, double-course and multiple-course (p < 0.05). In terms of time period, over one-year group, the improvement of multi-course treatment was more significant than single and double-course. In terms of comprehensive efficacy, WMT restored 32.14% of patients in hyperlipidemia group to normal lipid group (p < 0.001), of which 30.00% recovered to normal lipid group within one-year (p = 0.004), and 65.38% reassigned to normal lipid group over one-year (p = 0.003). In addition, over one-year treatment, WMT significantly degraded the high-risk and the medium-risk group of ASCVD risk stratification in hyperlipidemia cases. There were no serious adverse events.
CONCLUSIONS
WMT had a long-term improvement effect on patients with hyperlipidemia. The effect of multiple courses over one year was more significant than that of single/double courses and also had a significant de-stratification effect on the risk of ASCVD with high safety. Therefore, WMT provides a safe and long-term effective clinical treatment for patients with dyslipidemia.
PubMed: 38920288
DOI: 10.14309/ctg.0000000000000735 -
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 -
BMB Reports Jun 2024The heterotrimeric molecular motor kinesin-2 is involved in the microtubule-dependent transport of intracellular cargo. It consists of two distinct motor subunits...
The heterotrimeric molecular motor kinesin-2 is involved in the microtubule-dependent transport of intracellular cargo. It consists of two distinct motor subunits (KIF3A, and KIF3B) and a non-motor subunit, kinesin-associated protein 3 (KAP3). The cargo-binding domain (CBD) at the carboxyl (C)-terminus of KIF3s plays an important role in the interaction with several different binding proteins. To identify the binding proteins for heterotrimeric kinesin-2, we performed a yeast two-hybrid screen and found a new interaction with Disables-1 (Dab1), the intracellular adaptor protein of reelin receptors. Dab1 bound to the CBD of KIF3A, but did not interact with the C-terminal domain of KIF3B, KIF5B, KIF17 or KAP3. The phosphotyrosine binding (PTB) domain-containing region of Dab1 is essential for the interaction with KIF3A. KIF3A interacted with GST-Dab1, and GST-CaMKIIα, but did not interact with GST-apolipoprotein E receptor 2 (ApoER2)-C or with GST alone. When co-expressed in HEK-293T cells, KIF3A co-precipitated with Dab1, but not with KIF5B. Dab1 and KIF3A were co-localized in cultured cells. We also identified deduced cell surface expression of ApoER2 in KIF3A dominant-negative cells. These results suggest that the KIF3A plays a role in the intracellular trafficking of ApoER2 to the cell surface.
PubMed: 38919020
DOI: No ID Found -
BMC Neuroscience Jun 2024Diabetes raises the risk of dementia, mortality, and cognitive decline in the elderly, potentially because of hereditary variables such as APOE. In this study, we aim to... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIM
Diabetes raises the risk of dementia, mortality, and cognitive decline in the elderly, potentially because of hereditary variables such as APOE. In this study, we aim to evaluate Diabetes mellitus and the risk of incident dementia in APOE ɛ4 carriers.
METHOD
We thoroughly searched PubMed (Medline), Scopus, and Google Scholar databases for related articles up to September 2023. The titles, abstracts, and full texts of articles were reviewed; data were extracted and analyzed.
RESULT
This meta-analysis included nine cohorts and seven cross-sectional articles with a total of 42,390 population. The study found that APOE ɛ4 carriers with type 2 diabetes (T2D) had a 48% higher risk of developing dementia compared to non-diabetic carriers (Hazard Ratio;1.48, 95%CI1.36-1.60). The frequency of dementia was 3 in 10 people (frequency: 0.3; 95%CI (0.15-0.48). No significant heterogeneity was observed. Egger's test, which we performed, revealed no indication of publication bias among the included articles (p = 0.2).
CONCLUSION
Overall, diabetes increases the risk of dementia, but further large-scale studies are still required to support the results of current research.
Topics: Humans; Dementia; Apolipoprotein E4; Diabetes Mellitus, Type 2; Heterozygote; Risk Factors; Incidence
PubMed: 38918708
DOI: 10.1186/s12868-024-00878-9 -
BioRxiv : the Preprint Server For... Jun 2024The effects of sex, race, and Apolipoprotein E ( ) - Alzheimer's disease (AD) risk factors - on white matter integrity are not well characterized. Diffusion MRI data...
INTRODUCTION
The effects of sex, race, and Apolipoprotein E ( ) - Alzheimer's disease (AD) risk factors - on white matter integrity are not well characterized. Diffusion MRI data from nine well-established longitudinal cohorts of aging were free-water (FW)-corrected and harmonized. This dataset included 4,702 participants (age=73.06 ± 9.75) with 9,671 imaging sessions over time. FW and FW-corrected fractional anisotropy (FA ) were used to assess differences in white matter microstructure by sex, race, and ε4 carrier status. Sex differences in FA in association and projection tracts, racial differences in FA in projection tracts, and ε4 differences in FW limbic and occipital transcallosal tracts were most pronounced. There are prominent differences in white matter microstructure by sex, race, and ε4 carrier status. This work adds to our understanding of disparities in AD. Additional work to understand the etiology of these differences is warranted. Sex, race, and ε4 carrier status relate to white matter microstructural integrity Females generally have lower FA compared to males Non-Hispanic Black adults generally have lower FA than non-Hispanic White adults ε4 carriers tended to have higher FW than non-carriers The authors used PubMed and Google Scholar to review literature that used conventional and free-water (FW)-corrected microstructural metrics to evaluate sex, race, and ε4 differences in white matter microstructure. While studies have previously explored differences by sex and ε4 status, less is known about racial differences and no large-scale FW-corrected analysis has been performed. Sex and race were more associated with FA while ε4 status was associated with FW metrics. Association, projection, limbic, and occipital transcallosal tracts showed the greatest differences. Future studies to determine the biological and social pathways that lead to sex, racial, and ε4 differences are warranted.
CONSENT STATEMENT
All participants provided informed consent in their respective cohort studies.
PubMed: 38915636
DOI: 10.1101/2024.06.10.598357 -
Clinical Kidney Journal Jun 2024
PubMed: 38915437
DOI: 10.1093/ckj/sfae161 -
International Journal of STD & AIDS Jun 2024We sought to determine the prevalence of sickle cell trait (SCT) and apolipoprotein-1 ( risk variants in people living with HIV (PLWH) in Nigeria, and to establish if...
BACKGROUND
We sought to determine the prevalence of sickle cell trait (SCT) and apolipoprotein-1 ( risk variants in people living with HIV (PLWH) in Nigeria, and to establish if SCT and high-risk status correlate with estimated glomerular filtration rate (eGFR) and/or prevalent chronic kidney disease (CKD).
METHODS
Baseline demographic and clinical data were obtained during three cross-sectional visits. CKD was defined as having an eGFR<60 mL/min/1.73 m. We collected urine specimens to determine urine albumin-creatine ratio and blood samples for sickle cell genotyping, testing, and for creatinine/cystatin C assessment. The associations between SCT, genotype, and eGFR/CKD stages/CKD were investigated using linear/ordinal logistic/logistic regression models, respectively.
RESULTS
Of 2443 participants, 599 (24.5%) had SCT, and 2291 (93.8%) had a low-risk genotype (0 or 1 risk variant), while 152 (6.2%) had high-risk genotype (2 allele copies). In total, 108 participants (4.4%) were diagnosed with CKD. In adjusted analyses, SCT was associated with lower eGFR (adjusted mean difference [aMD]= -2.33, 95% CI -4.25, -0.42), but not with worse CKD stages, or increased odds of developing CKD. Participants with the high risk genotype were more likely to have lower eGFR (aMD= -5.45, 95% CI -8.87, -2.03), to develop CKD (adjusted odds ratio [aOR] = 1.97, 95% CI: 1.03, 3.75), and to be in worse CKD stages (aOR = 1.60, 95% CI: 1.12, 2.29) than those with the low-risk genotype. There was no evidence of interaction between SCT and genotype on eGFR or risk of CKD.
CONCLUSION
Our findings highlight the multifaceted interplay of genetic factors in the pathogenesis of CKD in PLWH.
PubMed: 38915133
DOI: 10.1177/09564624241262397 -
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 -
Sexually Transmitted Infections Jun 2024The 2022 global outbreak of monkeypox virus (MPXV), previously confined to Central and West Africa, necessitates an enhanced understanding of its spread. Comprehensive...
OBJECTIVES
The 2022 global outbreak of monkeypox virus (MPXV), previously confined to Central and West Africa, necessitates an enhanced understanding of its spread. Comprehensive genomic surveillance to understand the virus's evolution and spread is needed, particularly in Asia.
METHODS
Genomic data from 169 MPXV genome sequences in Asia were analysed. Through advanced genomic sequencing of clinical samples, we analysed the distribution and mutations of MPXV lineages in Asia.
RESULTS
Phylogenetic analysis revealed a distinct clustering of C.1 strains rise in Northeast Asia in 2023, while genomic examination identified specific consensus mutations like R84K, R665C and L16F in C.1 strains. The mutations, coupled with an increased rate of apolipoprotein B mRNA-editing catalytic polypeptide-like 3 motif G-to-A mutations in C.1 (OR 24.87±8.81), indicate a potential adaptation mechanism.
CONCLUSIONS
Our findings underscore the need for ongoing surveillance and provide vital insights into MPXV's evolving dynamics, aiding in public health strategy formulation against this emerging infectious threat.
PubMed: 38914476
DOI: 10.1136/sextrans-2024-056119