Impact of risk factors on intervened and non-intervened coronary lesions.

INTRODUCTION: In-stent restenosis (ISR) and aggravated non-intervened coronary lesions (ANL) are two pivotal aspects of disease progression in patients with coronary artery disease (CAD). Established risk factors for both include hyperlipidemia, hypertension, diabetes, chronic kidney disease, and smoking. However, there is limited research on the comparative risk factors for the progression of these two aspects of progression. The aim of this study was to analyze and compare the different impacts of identical risk factors on ISR and ANL. METHODS: This study enrolled a total of 510 patients with multiple coronary artery lesions who underwent repeated coronary angiography (CAG). All patients had previously undergone percutaneous coronary intervention (PCI) and presented non-intervened coronary lesions in addition to the previously intervened vessels. RESULTS: After data analysis, it was determined that HbA1c (OR 1.229, 95% CI 1.022-1.477, P=0.028) and UA (OR 1.003, 95% CI 1.000-1.005, P=0.024) were identified as independent risk factors for ISR. Furthermore, HbA1c (OR 1.215, 95% CI 1.010-1.460, P=0.039), Scr (OR 1.007, 95% CI 1.003-1.017, P=0.009), and ApoB (OR 1.017, 95% CI 1.006-1.029, P=0.004) were identified as independent risk factors for ANL. The distribution of multiple blood lipid levels differed between the ANL only group and the ISR only group. Non-HDL-C (2.17 mmol/L vs. 2.44 mmol/L, P=0.007) and ApoB (63.5 mg/dL vs. 71.0 mg/dL, P=0.011) exhibited significantly higher values in the ANL only group compared to the ISR only group. CONCLUSIONS: Blood glucose levels and chronic kidney disease were identified as independent risk factors for both ISR and ANL, while elevated lipid levels were only significantly associated with ANL. In patients with non-intervened coronary lesions following PCI, it is crucial to assess the concentration of non-HDL-C and ApoB as they serve as significant risk factors.

Angiopoietin-like Proteins and Lipoprotein Lipase: The Waltz Partners That Govern Triglyceride-Rich Lipoprotein Metabolism? Impact on Atherogenesis, Dietary Interventions, and Emerging Therapies.

Over 50% of patients who take statins are still at risk of developing atherosclerotic cardiovascular disease (ASCVD) and do not achieve their goal LDL-C levels. This residual risk is largely dependent on triglyceride-rich lipoproteins (TRL) and their remnants. In essence, remnant cholesterol-rich chylomicron (CM) and very-low-density lipoprotein (VLDL) particles play a role in atherogenesis. These remnants increase when lipoprotein lipase (LPL) activity is inhibited. ApoCIII has been thoroughly studied as a chief inhibitor and therapeutic options to curb its effect are available. On top of apoCIII regulation of LPL activity, there is a more precise control of LPL in various tissues, which makes it easier to physiologically divide the TRL burden according to the body's requirements. In general, oxidative tissues such as skeletal and cardiac muscle preferentially take up lipids during fasting. Conversely, LPL activity in adipocytes increases significantly after feeding, while its activity in oxidative tissues decreases concurrently. This perspective addresses the recent improvements in our understanding of circadian LPL regulations and their therapeutic implications. Three major tissue-specific lipolysis regulators have been identified: ANGPTL3, ANGPTL4, and ANGPTL8. Briefly, during the postprandial phase, liver ANGPTL8 acts on ANGPTL3 (which is released continuously from the liver) to inhibit LPL in the heart and muscle through an endocrine mechanism. On the other hand, when fasting, ANGPTL4, which is released by adipocytes, inhibits lipoprotein lipase in adipose tissue in a paracrine manner. ANGPTL3 inhibitors may play a therapeutic role in the treatment of hypertriglyceridemia. Several approaches are under development. We look forward to future studies to clarify (a) the nature of hormonal and nutritional factors that determine ANGPTL3, 4, and 8 activities, along with what long-term impacts may be expected if their regulation is impaired pharmacologically; (b) the understanding of the quantitative hierarchy and interaction of the regulatory actions of apoCIII, apoAV, and ANGPTL on LPL activity; (c) strategies for the safe and proper treatment of postprandial lipemia; and (d) the effect of fructose restriction on ANGPTL3, ANGPTL4, and ANGPTL8.

The Impact of Pinus koraiensis Leaf Extract Consumption on Postprandial ApoB100 and Lipid Metabolism: A Randomized, Double-Blind, Placebo-Controlled Trial in Healthy Participants Subjected to an Oral High-Fat Challenge.

Pinus koraiensis (PK) leaf extract, derived from Korean pine byproducts, holds promise for alleviating postprandial hyperlipidemia. In this study, we investigated the potential of PK leaf extract for modulating postprandial hyperlipidemia in adults with normal or borderline fasting triglyceride levels. In a randomized, double-blind, parallel design, 70 subjects were randomly assigned to either the placebo or PK group for 4 weeks. After 4 weeks of consuming PK leaf extract, the results indicated a trend toward decreased serum apolipoprotein B-100 (ApoB100) levels 2 h after a high-fat challenge. Furthermore, significant improvements were observed in the incremental area under the curve (iAUC) at 0-4 h and 2-4 h compared to baseline, particularly among individuals with a higher body weight (>61.35 kg) and daily caloric intake (>1276.5 kcal). Based on these findings, PK leaf extract may have beneficial effects on postprandial lipoprotein metabolism, especially among individuals with a relatively high body weight and caloric intake.

Correlation Analysis of ApoB, ApoA1, and ApoB/ApoA1 with Cortical Morphology in Patients with Memory Complaints.

Background: Apolipoproteins and cortical morphology are closely associated with memory complaints, and both may contribute to the development of Alzheimer's disease. Objective: To examine whether apolipoprotein B (ApoB), apolipoprotein A-1 (ApoA1), and their ratio (ApoB/ApoA1) are associated with cortical morphology in patients with memory complaints. Methods: Ninety-seven patients underwent neuropsychological testing, measurements of ApoB, ApoA1, ApoB/ApoA1, plasma Alzheimer's biomarker, apolipoprotein E (ApoE) genotyping, and 3T structural magnetic resonance imaging (sMRI) scans. Based on sMRI scanning locations, patients were categorized into the University of Electronic Science and Technology (UESTC) and the Fourth People's Hospital of Chengdu (FPHC). The Computational Anatomy Toolbox within Statistical Parametric Mapping was used to calculate each patient's cortical morphology index based on sMRI data. The cortical morphology index and apolipoproteins were also analyzed. Results: Significant positive correlations were found between ApoB and sulcal depth in the lateral occipital cortex among the UESTC, the FPHC, and the total sample groups, and negative correlations were observed between sulcal depth in the lateral occipital cortex and the scores of the Shape Trails Test Part A and B. In the FPHC group, the scores of the Montreal Cognitive Assessment Basic, delayed recall of the Auditory Verbal Learning Test, Animal Fluency Test and Boston Naming Test were positively correlated with the sulcal depth. Conclusions: ApoB is associated with the sulcal depth in the lateral occipital cortex, potentially relating to speed/executive function in individuals with memory complaints.

APOBEC-1 Complementation Factor: From RNA Binding to Cancer.

BACKGROUND: APOBEC-1 complementation factor (A1CF) and Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-1 (APOBEC-1) constitute the minimal proteins necessary for the editing of apolipoprotein B (apoB) mRNA in vitro. Unlike APOBEC-1 and apoB mRNA, the ubiquitous expression of A1CF in human tissues suggests its unique biological significance, with various factors such as protein kinase C, thyroid hormones, and insulin regulating the activity and expression of A1CF. Nevertheless, few studies have provided an overview of this topic. OBJECTIVE: We conducted a literature review to describe the molecular mechanisms of A1CF and its relevance to human diseases. METHOD: In the PubMed database, we used the keywords 'A1CF' and 'APOBEC-1 complementation factor' to collect peer-reviewed articles published in English from 2000 to 2023. Two authors independently reviewed the articles and reached the consensus. RESULT: After reviewing 127 articles, a total of 61 articles that met the inclusion criteria were included in the present review. Studies revealed that A1CF is involved in epigenetic regulation of reproductive cells affecting embryonic development, and that it is closely associated with the occurrence of gout due to its editing properties on apoB. A1CF can also affect the process of epithelial-mesenchymal transition in renal tubular epithelial cells and promote liver regeneration by controlling the stability of IL-6 mRNA, but no influence on cardiac function was found. Furthermore, increasing evidence suggests that A1CF may promote the occurrence and development of breast cancer, lung cancer, renal cell carcinoma, hepatocellular carcinoma, endometrial cancer, and glioma. CONCLUSION: This review clarifies the association between A1CF and other complementary factors and their impact on the development of human diseases, aiming to provide guidance for further research on A1CF, which can help treat human diseases and promote health.

MicroRNA-615-3p decreases apo B expression in human liver cells.

Plasma lipids are mainly carried in apolipoprotein B (apoB) containing lipoproteins. High levels of these lipoproteins are associated with several metabolic diseases and lowering their plasma levels are associated with reduced incidence of atherosclerotic cardiovascular disease. MicroRNAs (miRs) are small non-coding RNAs that reduce protein expression of their target mRNAs and are potential therapeutic agents. Here, we identified a novel miR-615-3p that interacts with human 3'-UTR of apoB mRNA, induces post-transcriptional mRNA degradation, and reduces cellular and secreted apoB100 in human hepatoma Huh-7 cells. Reducing cellular miR-615-3p levels by CRISPR-sgRNA increased cellular and secreted apoB100 indicating endogenous miR regulates apoB expression. Overexpression of miR-615-3p along with or without palmitic acid treatment decreased cellular and media apoB and increased cellular triglyceride levels without inducing endoplasmic reticulum stress. These studies have identified miR-615-3p as a negative regulator of apoB expression in human liver derived cells. It is likely that there are more miRs that regulate apoB-containing lipoprotein assembly and secretion. Discovery of additional miRs may uncover novel mechanisms that control lipoprotein assembly and secretion.

Gene Mutation in Patients with Familial Hypercholesterolemia and Response to Alirocumab Treatment-A Single-Centre Analysis.

Background: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder characterized by significantly elevated levels of low-density lipoprotein (LDL) cholesterol, which plays a major role in the progression of atherosclerosis and leads to a heightened risk of premature atherosclerotic cardiovascular disease. Methods: We have carried out an observational study on a group of 17 patients treated at the Outpatient Lipid Clinic from 2019 to 2024. Result: The most frequent mutation observed was found in the LDL receptor (LDLR) gene, which was identified in ten patients (58.8%). Five patients were identified to have a mutation in the apolipoprotein B (APOB) gene, whereas two patients had two points mutations, one in the LDLR, and the other in the APOB gene. The average age of patients with LDLR mutation was 54.8 (12.3); for APOB mutation it was 61.4 (9.3) and for patients with two points mutation it was 61.5 (14.8). The study results showed that at Week 12, individuals with LDLR-defective heterozygotes who were given alirocumab 150 mg every two weeks experienced a 63.0% reduction in LDL cholesterol levels. On the other hand, individuals with APOB heterozygotes experienced a 59% reduction in LDL cholesterol levels. However, in patients with double heterozygous for mutations in LDLR and APOB genes, there was a hyporesponsiveness to alirocumab, and the reduction in LDL-C was only by 23% in two individuals. Conclusions: In patients with a single mutation, there was a greater response to treatment with alirocumab in contrast to patients with double heterozygous mutation, who did not respond to treatment with PCSK9 inhibitors.

Extracellular vesicles loaded with ApoB-100 protein affect the occurrence of coronary heart disease in patients after injury of spinal cord.

Spinal cord injury (SCI) patients have an increased susceptibility to coronary heart disease (CHD) due to dysregulated lipid deposition. We conducted a comprehensive investigation to gain insights into the specific roles of Apolipoprotein B-100 (APOB-100) in the development of CHD in patients suffering from SCI. First, we established an SCI rat model through semitransection. APOB-100 expression in plasma exosomes obtained from patients were determined. Subsequently, we found APOB-100 affected macrophage polarization when treating co-cultured neurons/macrophages lacking Sortilin with extracellular vesicles derived from SCI rats, where APOB-100 co-immunoprecipitated with Sortilin. Moreover, APOB-100 upregulation reduced neuronal cell viability and triggered apoptosis by upregulating Sortilin, leading to a decline in the Basso, Beattie, and Bresnahan (BBB) scale, exacerbation of neuron injury, increased macrophage infiltration, and elevated blood lipid-related indicators in SCI rats, which could be reversed by silencing Sortilin. In conclusion, APOB-100 from post-SCI patients' extracellular vesicles upregulates Sortilin, thereby endangering those patients to CHD.

Enhanced atherosclerosis in apolipoprotein E knockout rabbits: role of apoB48-rich remnant lipoproteins.

Introduction: Apolipoprotein E (apoE) acts as a binding molecule for both the low-density lipoprotein receptor and the lipoprotein receptor-related protein and this function is essential for facilitating the hepatocyte uptake of lipoproteins containing apoB. The absence of apoE leads to increased atherogenicity in both humans and mice, although the precise molecular mechanisms remain incompletely understood. Objectives: This study aimed to investigate the susceptibility of apoE knockout (KO) rabbits, in comparison with wild-type (WT) rabbits, to diet-induced hyperlipidemia and atherosclerosis. Methods: ApoE KO rabbits and WT rabbits were fed a diet containing 0.3% cholesterol for 16 weeks. Plasma lipid levels, lipoproteins, and apolipoproteins were analyzed. Atherosclerosis was evaluated at the endpoint of experiments. In addition, we evaluated the oxidizability of those lipoproteins containing apoB to investigate the possible mechanisms of atherosclerosis. Results: Male apoE KO rabbits showed significantly elevated levels of total cholesterol and triglycerides compared to WT rabbits, while female apoE KO rabbits displayed similar high total cholesterol levels, albeit with significantly higher triglycerides levels than WT controls. Notably, both male (2.1-fold increase) and female (1.6-fold increase) apoE KO rabbits exhibited a significantly augmented aortic lesion area compared to WT controls. Pathological examination showed that the increased intimal lesions in apoE KO rabbits were featured by heightened infiltration of macrophages (2.7-fold increase) and smooth muscle cells (2.5-fold increase). Furthermore, coronary atherosclerotic lesions were also increased by 1.3-fold in apoE KO rabbits. Lipoprotein analysis revealed that apoB48-rich beta-very-low-density lipoproteins were notably abundant in apoE KO rabbits, suggesting that these remnant lipoproteins of intestinal origin serve as the primary atherogenic lipoproteins. Moreover, apoB48-rich remnant lipoproteins isolated from apoE KO rabbits exhibited heightened susceptibility to copper-induced oxidation. Conclusions: The findings indicate that apoB48-rich remnant lipoproteins, resulting from apoE deficiency, possess greater atherogenic potential than apoB100-rich remnant lipoproteins, regardless of plasma TC levels.

Genetic association of lipids and lipid-lowering drug target genes with Endometrial carcinoma: a drug target Mendelian randomization study.

Background: Aberrant lipid metabolism is intricately linked to the development of endometrial cancer, and statin lipid-lowering medications are regarded as promising adjunctive therapies for future management of this malignancy. This study employed Mendelian randomization (MR) to explore the causal association between lipid traits and endometrial cancer while assessing the potential impact of drug targets on lower lipids on endometrial cancer. Method: Two-sample Mendelian randomization was employed to probe the causal association between lipid traits and endometrial carcinoma. Drug-target Mendelian randomization was also utilized to identify potential drug-target genes for managing endometrial carcinoma. In instances where lipid-mediated effects through particular drug targets were notable, the impacts of these drug targets on endometrial carcinoma risk factors were investigated to bolster the findings. Result: No causal association between genetically predicted lipid traits (LDL-C, TG, TC, and HDL-C) and EC was found in two-sample Mendelian randomization. In drug target Mendelian randomization, genetic modeling of apolipoprotein B (APOB) (OR [95%CI]=0.31, [0.16-0.60]; p=4.73e-04) and cholesteryl ester transfer protein (CETP) (OR [95%CI]=1.83, [1.38-2.43]; p=2.91e-05) genetic mimicry was associated with non-endometrioid carcinoma. Conclusion: The results of our MR study revealed no causal association between genetically predicted lipid traits (LDL-C, TG, TC, and HDL-C) and EC. Among the six lipid-lowering drug targets, we observed a significant association between lower predicted APOB levels and higher CETP levels with an increased risk of endometrioid carcinoma. These findings provide novel insights into the importance of lipid regulation in individuals with endometrial carcinoma, warranting further clinical validation and mechanistic investigations.

Proteogenomic Analysis Identifies a Causal Association between Plasma Apolipoprotein B Levels and Liver Cancer Risk.

Liver oncogenesis is accompanied by discernible protein changes in the bloodstream. By employing plasma proteomic profiling, we can delve into the molecular mechanisms of liver cancer and pinpoint potential biomarkers. In this nested case-control study, we applied liquid chromatography-tandem mass spectrometry for proteome profiling in baseline plasma samples. Differential protein expression was determined and was subjected to functional enrichment, network, and Mendelian randomization (MR) analyses. We identified 193 proteins with notable differential levels between the groups. Of these proteins, MR analysis offered a compelling negative association between apolipoprotein B (APOB) and liver cancer. This association was further corroborated in the UK Biobank cohort: genetically predicted APOB levels were associated with a 31% (95% CI 19-42%) decreased risk of liver cancer; and phenotypic analysis indicated an 11% (95% CI 8-14%) decreased liver cancer risk for every 0.1 g/L increase of circulating APOB levels. Multivariable MR analysis suggested that the hepatic fat content might fully mediate the APOB-liver cancer connection. In summary, we identified some plasma proteins, particularly APOB, as potential biomarkers of liver cancer. Our findings underscore the intricate link between lipid metabolism and liver cancer, offering hints for targeted prophylactic strategies and early detection.

Mechanisms modulating foam cell formation in the arterial intima: exploring new therapeutic opportunities in atherosclerosis.

In recent years, the role of macrophages as the primary cell type contributing to foam cell formation and atheroma plaque development has been widely acknowledged. However, it has been long recognized that diffuse intimal thickening (DIM), which precedes the formation of early fatty streaks in humans, primarily consists of lipid-loaded smooth muscle cells (SMCs) and their secreted proteoglycans. Recent studies have further supported the notion that SMCs constitute the majority of foam cells in advanced atherosclerotic plaques. Given that SMCs are a major component of the vascular wall, they serve as a significant source of microvesicles and exosomes, which have the potential to regulate the physiology of other vascular cells. Notably, more than half of the foam cells present in atherosclerotic lesions are of SMC origin. In this review, we describe several mechanisms underlying the formation of intimal foam-like cells in atherosclerotic plaques. Based on these mechanisms, we discuss novel therapeutic approaches that have been developed to regulate the generation of intimal foam-like cells. These innovative strategies hold promise for improving the management of atherosclerosis in the near future.

Differential distribution of plasma apoA-I and apoB levels and clinical significance of apoB/apoA-I ratio in ischemic stroke subtypes.

Background and purpose: Ischemic stroke (IS) is classified into clinical subtypes and likely influenced by various lipid components. Nevertheless, the roles of apolipoprotein A-I (apoA-I), apolipoprotein B (apoB), and apoB/apoA-I ratio in different IS subtypes remain underexplored. This study aimed to investigate the differential distribution of plasma apoA-I and apoB levels among IS subtypes and to evaluate the predictive value of the apoB/apoA-I ratio in assessing IS subtypes and disease severity. Methods: In this study, 406 IS patients were categorized into three IS-subtypes based on clinical manifestations and imaging assessment, including intracranial atherosclerosis-related IS patients (ICAS, n = 193), extracranial atherosclerosis-related IS patients (ECAS, n = 111), and small artery occlusion-related IS patients (SAO, n = 102). Plasma apoA-I and apoB levels were measured upon hospital admission. Random forest (RF) models were performed to assess predictive values of these apolipoproteins apoB, apoA-I and their ratio in assessing IS subtype stratification and disease severity. Results: Serum apoA-I levels were significantly lower in ICAS compared to ECAS and SAO patients (p < 0.0001), while apoB levels were higher in ICAS patients (p < 0.0001). The apoB/apoA-I ratio was significantly higher in ICAS compared to ECAS and SAO patients (p < 0.0001). Correlation analyses found a significant correlation between the apoB/apoA-I ratio and conventional lipid components. Additionally, RF models and plots of variable importance and distribution of minimal depth revealed that the apoB/apoA-I ratio played the most influential predictor in predicting IS subtypes and stenosis severity. Conclusion: Our study shows the differential distribution of apoA-I and apoB IS subtypes and reveals the significance of the apoB/apoA-I ratio in assessing IS subtypes and arterial stenosis severity. Further studies are warranted to validate these findings and enhance their clinical applicability.

Research Hotspots and Development Trends on Apolipoprotein B in the Field of Atherosclerosis: A Bibliometric Analysis.

BACKGROUND: Cardiovascular diseases caused by atherosclerosis (AS) are the leading causes of disability and death worldwide. Apolipoprotein B (ApoB), the core protein of low-density lipoproteins, is a major contributor to cardiovascular disease-related morbidity and mortality, with apolipoprotein B (ApoB) playing a critical role in its pathogenesis. However, no bibliometric studies on the involvement of ApoB in AS have been published. This study aimed to conduct a comprehensive bibliometric analysis to explore the current and future trends regarding the role of ApoB in AS. METHODS: Utilizing the Web of Science Core Collection, a thorough search was conducted for ApoB in AS-related papers related to research on ApoB in the field of AS during 1991-2023. The analysis focused on annual publication trends, leading countries/regions and institutions, influential authors, journal and key journals. CiteSpace and VOSviewer were employed to visualize reference co-citations, and keyword co-occurrences, offering insights into the research landscape and emerging trends. RESULTS: This bibliometric analysis employed network diagrams for cluster analysis of a total of 2105 articles and reviews, evidencing a discernible upward trend in annual publication volume. This corpus of research emanates from 76 countries/regions and 2343 organizations, illustrating the widespread international engagement in ApoB-related AS studies. Notably, the United States and the University of California emerge as the most prolific contributors, which underscores their pivotal roles in advancing this research domain. The thematic investigation has increasingly focused on elucidating the mechanistic involvement of ApoB in atherosclerosis, its potential as a diagnostic biomarker, and its implications for therapeutic strategies. CONCLUSION: This bibliometric analysis provides the first comprehensive perspective on the evolving promise of ApoB in AS-related research, emphasizing the importance of this molecule in opening up new diagnostic and therapeutic avenues. This study emphasizes the need for continued research and interdisciplinary efforts to strengthen the fight against AS. Furthermore, it emphasizes the critical role of international collaboration and interdisciplinary exploration in leveraging new insights to achieve clinical breakthroughs, thereby addressing the complexities of AS by focusing on ApoB.

The effect of pulmonary rehabilitation on cardiovascular risk, oxidative stress and systemic inflammation in patients with COPD.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is a leading cause of death, and cardiovascular (CV) comorbidities play a role. Evidence of the pulmonary rehabilitation (PR) effect in reducing the CV risk (CVR) in COPD patients is limited. In this study, we aimed to determine the impact of an 8-week PR program (PRP) on the CVR of the overall population and to compare the impact on the exacerbator versus non-exacerbator patients. PATIENTS AND METHODS: This was a prospective study that included adults who had post-bronchodilator forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) (FEV1/FVC) ratio <70 % and FEV1 <80 % predicted, had quit smoking for at least 1 year and had a history of tobacco consumption greater than 10 packs/year, and were clinically stable in the last 8 weeks. Pre- and post-PRP assessments included respiratory function evaluation, laboratory tests, and exercise capacity assessment (6-min walking test [6MWT]). CVR was assessed using different risk prediction models. RESULTS: A total of 50 patients (28 exacerbators and 22 non-exacerbators) completed the PRP (median age: 64.5 years, men: 72 %; arterial hypertension: 70 %, dyslipidemia: 30 %, diabetes: 20 %; CV disease (CVD): 24 %. After the PRP, exacerbator patients showed a significant decrease in the CVR calculated by the COPDCoRi model (p < 0.001); patients with ≥30-m increase on the 6MWT showed statistically significant lower levels of glucose (p = 0.004), HbA1c (p = 0.004) and BODE index score (p = 0.026) compared to patients with <30-m increase. CONCLUSIONS: PR reduced certain modifiable CVR factors and CVD risk, especially in exacerbator patients.

Early-onset Parkinson's disease with mutations in both the PRKN gene and the APOB gene: A case report. / PRKNåŸºå› åˆå¹¶APOBåŸºå› çªå˜çš„æ—©å‘åž‹å¸•é‡‘æ£®ç— 1例.

The incidence rate of Parkinson's disease ranks the second among degenerative diseases of the nervous system, only lower than Alzheimer's disease. Early-onset Parkinson's disease (EPOD) refers to Parkinson's disease with initial symptoms appearing before the age of 50. EOPD is associated with certain genetic mutations and has distinct clinical features. This study reports a case of EOPD with mutations in both the PRKN and the APOB genes. The patient presented with the initial symptom of unstable walking at the age of 28, followed by bradykinesia, limb tremors, masked face, shuffling gait, and cogwheel rigidity in both upper limbs. The blood lipid test showed total cholesterol of 6.48 mmol/L and low-density lipoprotein cholesterol of 4.13 mmol/L. Genetic testing showed a deletion in exon 5 and a point mutation [c.850G>C(p.Gly284Arg)] in exon 7 of the PRKN gene, as well as a point mutation [c.10579C>T(p.Arg3527Trp)] in exon 26 of the APOB gene. Based on these clinical manifestations and examination results, the patient was diagnosed with EOPD. The compound heterozygous mutations in the PRKN gene, as well as the combined mutations in the PRKN and APOB genes, are both reported for the first time, expanding the spectrum of genetic mutations associated with EOPD.

Association of cerebrospinal fluid NPY with peripheral ApoA: a moderation effect of BMI.

BACKGROUND: Apoprotein A-I (ApoA-I) and Apoprotein B (ApoB) have emerged as novel cardiovascular risk biomarkers influenced by feeding behavior. Hypothalamic appetite peptides regulate feeding behavior and impact lipoprotein levels, which effects vary in different weight states. This study explores the intricate relationship between body mass index (BMI), hypothalamic appetite peptides, and apolipoproteins with emphasis on the moderating role of body weight in the association between neuropeptide Y (NPY), ghrelin, orexin A (OXA), oxytocin in cerebrospinal fluid (CSF) and peripheral ApoA-I and ApoB. METHODS: In this cross-sectional study, we included participants with a mean age of 31.77 ± 10.25 years, categorized into a normal weight (NW) (n = 73) and an overweight/obese (OW/OB) (n = 117) group based on BMI. NPY, ghrelin, OXA, and oxytocin levels in CSF were measured. RESULTS: In the NW group, peripheral ApoA-I levels were higher, while ApoB levels were lower than in the OW/OB group (all p < 0.05). CSF NPY exhibited a positive correlation with peripheral ApoA-I in the NW group (r = 0.39, p = 0.001). Notably, participants with higher CSF NPY levels had higher peripheral ApoA-I levels in the NW group and lower peripheral ApoA-I levels in the OW/OB group, showing the significant moderating effect of BMI on this association (R2 = 0.144, ß=-0.54, p < 0.001). The correlation between ghrelin, OXA and oxytocin in CSF and peripheral ApoB in both groups exhibited opposing trends (Ghrelin: r = -0.03 and r = 0.04; OXA: r = 0.23 and r=-0.01; Oxytocin: r=-0.09 and r = 0.04). CONCLUSION: This study provides hitherto undocumented evidence that BMI moderates the relationship between CSF NPY and peripheral ApoA-I levels. It also reveals the protective role of NPY in the NW population, contrasting with its risk factor role in the OW/OB population, which was associated with the at-risk for cardiovascular disease.

A retrospective study of Parkinson's disease in Southwest China 2021-2024: An age-based approach.

BACKGROUND: Globally, Parkinson's disease (PD) is one of the common neurodegenerative diseases in the elderly with increasing morbidity and disability, and its clinical pathogenesis is not clear. OBJECTIVE: To compare the differences in disease severity and blood biomarkers levels and their correlation between patients with early-onset Parkinson's disease (EOPD) and late-onset Parkinson's disease (LOPD). METHODS: A total of 342 patients diagnosed with PD were retrospectively collected. PD patients were categorized into EOPD (24 patients) and LOPD (318 patients) according to the age of onset of the disease. The Hoehn-Yahr (HY) staging was used to assess the severity of the disease in PD patients. Subjective rating scales such as the Mini-mental State Examination (MMSE) were used to assess the motor and non-motor functions of the patients. The differences of objective blood biomarkers such as triglyceride (TG) between the two groups were investigated. The correlation between them and PD was explored by logistic analysis. RESULTS: Percentage of EOPD group with HY staged as intermediate to late and Scales for Outcomes in Parkinson's Disease-Autonomic (SCOPA-AUT), Movement Disorder Society-Unified Parkinson's disease Rating Scale-III (MDS-UPDRS-III), Montreal Cognitive Assessment (MoCA) score and TG, non-high-density lipoprotein-cholesterol (N-HDL-C), homocysteine (HCY), apolipoprotein B (Apo-B), free triiodothyronine (FT3), free thyroxine (FT4), high-sensitivity C-reactive protein (hs-CRP) levels were lower than those in the LOPD group (P < 0.05); and the proportion of HY staged as early stage, Hamilton Anxiety Scale (HAMA) and Fatigue severity scale (FSS) scores and the levels of vitamin B12 were higher than those in the LOPD group (P < 0.05). The results of Multifactorial Logistic regression analysis showed that N-HDL-C [OR = 1.409, 95 % CI (1.063, 1.868)], Apo-B [OR = 0.797, 95 % CI (0.638, 0.997)], Vitamin B12 [OR = 0.992, 95 % CI (0.987, 0.998)] and hs-CRP [OR = 1.124, 95 % CI (1.070, 1.182)] were independent factors affecting the severity of PD, with significant differences between groups (P < 0.05). CONCLUSION: N-HDL-C, Apo-B, Vitamin B12, and hs-CRP levels play an important role in the progression of PD.