OBJECTIVE: Alzheimer\'s disease (AD) is the most-prevalent form of dementia and imposes substantial burdens at the personal and societal levels. The apolipoprotein E (APOE) ε4 allele is a genetic factor known to increase AD risk and exacerbate brain atrophy and its symptoms. We aimed to provide a comprehensive review of the impacts of APOE ε4 on brain atrophy in AD as well as in mild cognitive impairment (MCI) as a transitional stage of AD.
METHODS: We performed a coordinate-based meta-analysis of voxel-based morphometry studies to compare gray-matter atrophy patterns between carriers and noncarriers of APOE ε4. We obtained coordinate-based structural magnetic resonance imaging data from 1,135 individuals who met our inclusion criteria among 12 studies reported in PubMed and Google Scholar.
RESULTS: We found that atrophy of the hippocampus and parahippocampus was significantly greater in APOE ε4 carriers than in noncarriers, especially among those with AD and MCI, while there was no significant atrophy in these regions in healthy controls who were also carriers.
CONCLUSIONS: The present meta-analysis has highlighted the significant link between the APOE ε4 allele and hippocampal atrophy in both AD and MCI, which emphasizes the critical influence of the allele on neurodegeneration, especially in the hippocampus. These findings improve the understanding of AD pathology, potentially facilitating progress in early detection, targeted interventions, and personalized care strategies for individuals at risk of AD who carry the APOE ε4 allele.

Lipoprotein(a) (Lp(a)) is an atherogenic low-density lipoprotein (LDL)-like particle that is currently regarded as a non-modifiable risk factor for atherosclerotic cardiovascular disease. The number of patients detected with elevated Lp(a) concentrations has been increasing in recent years, although the implication of this finding is unclear for patients and physicians. We screened our lipid clinic database for patients aged >65 years with very high Lp(a) concentrations, which were defined as >230 nmol/L, and cardiovascular outcomes were assessed. The patients\' (n = 16) mean (±standard deviation) age was 72.2 ± 7.1 years and the mean Lp(a) concentration was 313 ± 68 nmol/L. After a cumulative 129.0 patient-year follow-up (mean: 8.1 ± 4.2 years), the mean age was 80.3 ± 7.0 years. We observed a low baseline prevalence of cardiovascular events, with only two patients having a history of cardiovascular events. Furthermore, zero incident adverse cardiovascular events were recorded over the follow-up. Therefore, very high Lp(a) concentrations and disease-free old age are not mutually exclusive. Our aggregated clinical experience is that there is only a modest association between elevated Lp(a) concentrations and adverse outcomes. Nonetheless, we still advise treating modifiable risk factors in these patients.

OBJECTIVE: Although various randomized controlled trials (RCTs) have evaluated the effect of raloxifene on apolipoproteins and lipoprotein(a) concentrations in postmenopausal women, the results have been inconsistent and inconclusive. Therefore, we conducted this meta-analysis of RCTs to investigate the effect of raloxifene administration on apolipoproteins and lipoprotein(a) [Lp(a)] concentrations in postmenopausal women.
METHODS: Two independent researchers systematically searched the scientific literature (including PubMed/Medline, Scopus, Web of Science, and EMBASE) for English-language randomized controlled trials (RCTs) published up to June 2024. We included RCTs reporting the impact of raloxifene on apolipoprotein A-I (ApoA-I), apolipoprotein B (ApoB), and Lp(a) levels in postmenopausal women. The primary outcome of interest was change in Lp(a), and the secondary outcomes were changes in ApoA-I and ApoB.
RESULTS: The present meta-analysis incorporated 12 publications with 14 RCT arms. The comprehensive outcomes derived from the random-effects model revealed a statistically significant increase in ApoA-I (WMD: 6.06 mg/dL, 95% CI: 4.38, 7.75, P < 0.001) and decrease in ApoB concentrations (WMD: -8.48 mg/dL, 95% CI: -10.60, -6.36, P < 0.001) and Lp(a) (WMD: -3.02 mg/dL, 95% CI: -4.83, -1.21, P < 0.001) following the administration of raloxifene in postmenopausal women. In the subgroup analyses, the increase in ApoA-I and the decrease in ApoB and Lp(a) levels were greater in RCTs with a mean participant age of ≥60 years and a duration of ≤12 weeks.
CONCLUSIONS: The current meta-analysis of RCTs demonstrates that treatment with raloxifene reduces ApoB and Lp(a) levels while increasing ApoA-I levels in postmenopausal women. Since these effects on lipid components are associated with a reduced risk of cardiovascular disease (CVD), raloxifene could be a suitable therapy for postmenopausal women who are at an increased risk of CVD and have other medical indications for raloxifene administration.

UNASSIGNED: Unexplained recurrent pregnancy loss (URPL) is a clinical dilemma in reproductive fields. Its diagnosis is mainly exclusionary after extensive clinical examination, and some of the patients may still face the risk of miscarriage.
UNASSIGNED: We analyzed follicular fluid (FF) from in vitro fertilization (IVF) in eight patients with URPL without endocrine abnormalities or verifiable causes of abortion and eight secondary infertility controls with no history of pregnancy loss who had experienced at least one normal pregnancy and delivery by direct data-independent acquisition (dDIA) quantitative proteomics to identify differentially expressed proteins (DEPs). In this study, bioinformatics analysis was performed using online software including g:profiler, String, and ToppGene. Cytoscape was used to construct the protein-protein interaction (PPI) network, and ELISA was used for validation.
UNASSIGNED: Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the DEPs are involved in the biological processes (BP) of complement and coagulation cascades. Apolipoproteins (APOs) are key proteins in the PPI network. ELISA confirmed that APOB was low-expressed in both the FF and peripheral blood of URPL patients.
UNASSIGNED: Dysregulation of the immune network intersecting coagulation and inflammatory response is an essential feature of URPL, and this disequilibrium exists as early as the oogenesis stage. Therefore, earlier intervention is necessary to prevent the development of URPL. Moreover, aberrant lipoprotein regulation appears to be a key factor contributing to URPL. The mechanism by which these factors are involved in the complement and coagulation cascade pathways remains to be further investigated, which also provides new candidate targets for URPL treatment.

BACKGROUND:  Prediabetes is defined as a hyperglycemic state between normal glucose metabolism and diabetes mellitus. It is also recognized as a predisposing factor for cardiovascular disease. Apolipoprotein is a constituent of lipoproteins, and its ratio levels (ApoB/ApoA1 ratio) are considered an independent risk factor for cardiovascular diseases. This study aimed to evaluate the apolipoprotein ratio (ApoB/ApoA1 ratio) and lipoprotein ratio (low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio) in prediabetes in relation to glycemic levels and establish the association between apolipoprotein and lipoprotein ratios in prediabetic individuals and their glycemic levels.
METHODS:  A case-control study was conducted among 150 participants, 75 with prediabetes and 75 apparently healthy individuals (with no prediabetes or diabetes), from January 1, 2023 to December 30, 2023. The parameters involved are fasting serum glucose, insulin, blood HbA1c%, HDL-C, LDL-C, apolipoprotein A, apolipoprotein B, and lipoprotein(a) (Lp(a)), measured using different principles.
RESULTS: Prediabetes was more predominant in males (58.7%), particularly those aged over 40 years (74.7%). The mean Lp(a) (46.18±11.66 mg/dl), LDL-C/HDL-C ratio (1.74±0.96), and ApoB/ApoA ratio (1.10±0.62) were significantly higher among prediabetic individuals. Moreover, these ratios were insignificantly higher in prediabetic individuals with HbA1c level (5.8-6.4%) and fasting glucose level (100-125 mg/dl) than those with lower levels.
CONCLUSIONS: Prediabetic individuals exhibited a notably elevated average level of Lp(a), as well as increased mean ApoB/ApoA1 ratio and mean LDL-C/HDL-C ratio compared to individuals who were apparently healthy.

The protective effect of high-density lipoprotein (HDL) on atherosclerosis is well known, and its mechanisms of action has been extensively studied. However, the impact of HDL on heart failure and its mechanisms are still controversial or unknown. The cardioprotective role of HDL may be reflected in its antioxidant, anti-inflammatory, anti-apoptotic, and endothelial function protection. In epidemiological studies, high-density lipoprotein cholesterol (HDL-C) levels have been negatively associated with heart failure (HF). The major protein component of HDL-C is apolipoprotein (Apo) A-I, while paraoxonase-1 (PON-1) is an essential mediator for many protective functions of HDL, and HDL may act through components like (Apo) A-I or PON-1 to delay heart failure progress. HDL can slow heart failure disease progression through parts like (Apo) A-I or PON-1. The potential causality between HDL and heart failure, the role of HDL in the pathogenesis of HF, and its interaction with C-reactive protein (CRP), triglycerides (TG), and monocytes in the process of heart failure have been briefly summarized and discussed in this article. HDL plays an important role in the pathogenesis, progression and treatment of HF.

Blood plasma is one of the most commonly analyzed and easily accessible biological samples. Here, we describe an automated liquid-liquid extraction platform that generates accurate, precise, and reproducible samples for metabolomic, lipidomic, and proteomic analyses from a single aliquot of plasma while minimizing hands-on time and avoiding contamination from plasticware. We applied mass spectrometry to examine the metabolome, lipidome, and proteome of 90 plasma samples to determine the effects of age, time of day, and a high-fat diet in mice. From 25 μl of mouse plasma, we identified 907 lipid species from 16 different lipid classes and subclasses, 233 polar metabolites, and 344 proteins. We found that the high-fat diet induced only mild changes in the polar metabolome, upregulated apolipoproteins, and induced substantial shifts in the lipidome, including a significant increase in arachidonic acid and a decrease in eicosapentaenoic acid content across all lipid classes.

UNASSIGNED: Post-stroke upper limb (UL) motor improvement is associated with adaptive neuroplasticity and motor learning. Both intervention-related (including provision of intensive, variable, and task-specific practice) and individual-specific factors (including the presence of genetic polymorphisms) influence improvement. In individuals with stroke, most commonly, polymorphisms are found in Brain Derived Neurotrophic Factor (BDNF), Apolipoprotein (APOE) and Catechol-O-Methyltransferase (COMT). These involve a replacement of cystine by arginine (APOEε4) or valines by 1 or 2 methionines (BDNF:val66met, met66met; COMT:val158met; met158met). However, the implications of these polymorphisms on post-stroke UL motor improvement specifically have not yet been elucidated.
UNASSIGNED: Examine the influence of genetic polymorphism on post-stroke UL motor improvement.
UNASSIGNED: Systematic Review and Meta-Analysis.
UNASSIGNED: We conducted a systematic search of the literature published in English language. The modified Downs and Black checklist helped assess study quality. We compared change in UL motor impairment and activity scores between individuals with and without the polymorphisms. Meta-analyses helped assess change in motor impairment (Fugl Meyer Assessment) scores based upon a minimum of 2 studies/time point. Effect sizes (ES) were quantified based upon the Rehabilitation Treatment Specification System as follows: small (0.08-0.18), medium (0.19 -0.40) and large (≥0.41).
UNASSIGNED: We retrieved 10 (4 good and 6 fair quality) studies. Compared to those with BDNF val66met and met66met polymorphism, meta-analyses revealed lower motor impairment (large ES) in those without the polymorphism at intervention completion (0.5, 95% CI: 0.11-0.88) and at retention (0.58, 95% CI:0.06-1.11). The presence of CoMT val158met or met158met polymorphism had similar results, with lower impairment (large ES ≥1.5) and higher activity scores (large ES ranging from 0.5-0.76) in those without the polymorphism. Presence of APOEε4 form did not influence UL motor improvement.
UNASSIGNED: Polymorphisms with the presence of 1 or 2 met alleles in BDNF and COMT negatively influence UL motor improvement.
UNASSIGNED: https://osf.io/wk9cf/.
This research paper focuses on the impact of variations in DNA sequence in certain genes on improvement seen in the arms in people who have had a stroke. In this study, we studied the role of 3 genes previously identified as having variations in DNA sequence. The authors searched published research articles from 2000 onwards and selected articles that satisfied certain criteria. We then checked the quality of the selected papers. Next, we combined common data from same tests used to examine motor improvement in the arms to check if there was an overall effect. A total of 10 papers were found. The selected articles were either good or moderate in quality. Variations in DNA structure in 2 out of the 3 genes studied affected the ability to improve the use of the arms in daily life after a stroke. Such information can have important implications in the extent of recovery that is possible after a stroke. It can also be helpful to decide the best rehabilitation options that can be offered to help maximize their ability to use the arms after a stroke.

Background: Breast cancer is the second most common cause of cancer-related mortality globally. Apolipoprotein L3 (APOL3), a member of the apolipoprotein family, has been implicated in the pathogenesis of cardiovascular diseases. Nevertheless, the functions and underlying mechanisms of APOL3 in breast cancer have yet to be elucidated. Methods: The patient data were sourced from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Quantitative real-time PCR (qRT-PCR), western blotting, and immunohistochemistry (IHC) assays were used to assess expression of APOL3. Cell proliferation rates were determined by Cell Counting Kit-8 (CCK-8) and colony formation assays. Flow cytometry was used to examine cell cycle distribution. Western blotting was conducted to investigate the expression of cell cycle related proteins. A xenograft model was used to evaluate the effect of APOL3 in vivo. APOL3-binding proteins were identified through mass spectrometry, co-immunoprecipitation (CO-IP) assay and immunofluorescence assay. Results: APOL3 expression was significantly downregulated in breast cancer, and its low expression was correlated with poor prognostic outcomes. Overexpression of APOL3 suppressed breast cancer cell proliferation, induced cell cycle disruption. Conversely, knockdown of APOL3 promoted cell proliferation. In vivo animal experiments demonstrated that APOL3 overexpression can inhibit tumor proliferation. Mass spectrometry, CO-IP and immunofluorescence assay confirmed the interaction between APOL3 and Y-box binding protein 1 (YBX1). Furthermore, YBX1 knockdown following APOL3 knockdown mitigated the enhanced proliferation. These results provide new ideas for clinically targeting APOL3 to inhibit proliferation in breast cancer. Conclusions: Our findings indicate that APOL3 inhibits breast cancer cell proliferation and cell cycle modulating P53 pathway through the interaction of YBX1.

Apolipoprotein-E4 (ApoE4) is an important genetic risk factor for Alzheimer\'s disease. The development of targeted-replacement human ApoE knock-in mice facilitates research into mechanisms by which ApoE4 affects the brain. We performed meta-analyses and meta-regression analyses to examine differences in cognitive performance between ApoE4 and ApoE3 mice. We included 61 studies in which at least one of the following tests was assessed: Morris Water Maze (MWM), novel object location (NL), novel object recognition (NO) and Fear Conditioning (FC) test. ApoE4 vs. ApoE3 mice performed significantly worse on the MWM (several outcomes, 0.17 ≤ g ≤ 0.60), NO (exploration, g=0.33; index, g=0.44) and FC (contextual, g=0.49). ApoE4 vs. ApoE3 differences were not systematically related to sex or age. We conclude that ApoE4 knock-in mice in a non-AD condition show some, but limited cognitive deficits, regardless of sex and age. These effects suggest an intrinsic vulnerability in ApoE4 mice that may become more pronounced under additional brain load, as seen in neurodegenerative diseases.