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Current Medical Science Jun 2024To investigate the serum lipid profiles of patients with localized osteosarcoma around the knee joint before and after neoadjuvant chemotherapy.
OBJECTIVE
To investigate the serum lipid profiles of patients with localized osteosarcoma around the knee joint before and after neoadjuvant chemotherapy.
METHODS
After retrospectively screening the data of 742 patients between January 2007 and July 2020, 50 patients aged 13 to 39 years with Enneking stage II disease were included in the study. Serum lipid levels, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein-α [Lp(a)], and apolipoprotein A1, B, and E (ApoA1, ApoB, and ApoE), and clinicopathological characteristics were collected before and after neoadjuvant chemotherapy.
RESULTS
The mean levels of TC, TG, and ApoB were significantly increased following neoadjuvant chemotherapy (16%, 38%, and 20%, respectively, vs. pretreatment values; P<0.01). The mean levels of LDL-C and ApoE were also 19% and 16% higher, respectively (P<0.05). No correlation was found between the pretreatment lipid profile and the histologic response to chemotherapy. An increase in Lp(a) was strongly correlated with the Ki-67 index (R=0.31, P=0.023). Moreover, a trend toward longer disease-free survival (DFS) was observed in patients with decreased TG and increased LDL-C following chemotherapy, although this difference was not statistically significant (P=0.23 and P=0.24, respectively).
CONCLUSION
Significant elevations in serum lipids were observed after neoadjuvant chemotherapy in patients with localized osteosarcoma. There was no prognostic significance of pretreatment serum lipid levels on histologic response to neoadjuvant chemotherapy. The scale of increase in serum Lp(a) might have a potential prognostic role in osteosarcoma. Patients with increased LDL-C or reduced TG after chemotherapy seem to exhibit a trend toward favorable DFS.
PubMed: 38926330
DOI: 10.1007/s11596-024-2852-8 -
The Science of the Total Environment Jun 2024Coal dust (CD) is a common pollutant, and epidemiological surveys indicate that long-term exposure to coal dust not only leads to the occurrence of pulmonary diseases...
Coal dust (CD) is a common pollutant, and epidemiological surveys indicate that long-term exposure to coal dust not only leads to the occurrence of pulmonary diseases but also has certain impacts on cognitive abilities. However, there is little open-published literature on the effects and specific mechanisms of coal dust exposure on the cognition of patients with Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD). An animal model has been built in this study with clinical population samples to explore the changes in neuroinflammation and cognitive abilities with coal dust exposure. In the animal model, compared to C57BL/6 mice, APP/PS1 mice exposed to coal dust exhibited more severe cognitive impairment, accompanied by significantly elevated levels of neuroinflammatory factors Apolipoprotein E4 (AOPE4) and Interleukin-6 (IL6) in the hippocampus, and more severe neuronal damage. In clinical sample sequencing, it was found that there is significant upregulation of AOPE4, neutrophils, and IL6 expression in the peripheral blood of MCI patients compared to normal individuals. Mechanistically, cell experiments revealed that IL6 could promote the phosphorylation of ERK1/2 and enhance the expression of transcription factor SP1, thereby promoting AOPE4 expression. The results of this study suggest that coal dust can promote the upregulation of IL6 and AOPE4 in patients, exacerbating cognitive impairment.
PubMed: 38925396
DOI: 10.1016/j.scitotenv.2024.174202 -
Arteriosclerosis, Thrombosis, and... Jul 2024In fitting with the American Heart Association’s 100th anniversary of its founding and organizing a Centennial Collection to celebrate this event, lipoprotein(a)... (Review)
Review
In fitting with the American Heart Association’s 100th anniversary of its founding and organizing a Centennial Collection to celebrate this event, lipoprotein(a) [Lp(a)] celebrates its 61 birthday in November 2024. There has been substantial progress in understanding the biology and pathophysiology of Lp(a) in the last 6 decades, including its discovery as a unique β-lipoprotein containing the pathognomonic apolipoprotein(a) moiety covalently bound to apolipoprotein B-100, its independent monogenetic association with cardiovascular disease and calcific aortic valve disease, its increased content of pro-atherogenic and pro-inflammatory of oxidized phospholipids relative to other lipoproteins and the development of RNA therapeutics to lower plasma Lp(a) levels. The validation or refutation of the “Lp(a) hypothesis”, namely that lowering plasma Lp(a) will lead to clinical benefit, is ongoing in 3 clinical outcomes trials. This essay reviews the discovery of Lp(a), summarizes the seminal pathophysiological findings since its discovery, discusses ongoing clinical trials with novel drugs and approaches, and provides a look ahead to unanswered questions.
Topics: Animals; Humans; Biomarkers; Cardiovascular Diseases; History, 21st Century; Lipoprotein(a)
PubMed: 38924439
DOI: 10.1161/ATVBAHA.124.319483 -
Science Translational Medicine Jun 2024Alzheimer's disease (AD) is currently defined by the aggregation of amyloid-β (Aβ) and tau proteins in the brain. Although biofluid biomarkers are available to measure...
Alzheimer's disease (AD) is currently defined by the aggregation of amyloid-β (Aβ) and tau proteins in the brain. Although biofluid biomarkers are available to measure Aβ and tau pathology, few markers are available to measure the complex pathophysiology that is associated with these two cardinal neuropathologies. Here, we characterized the proteomic landscape of cerebrospinal fluid (CSF) changes associated with Aβ and tau pathology in 300 individuals using two different proteomic technologies-tandem mass tag mass spectrometry and SomaScan. Integration of both data types allowed for generation of a robust protein coexpression network consisting of 34 modules derived from 5242 protein measurements, including disease-relevant modules associated with autophagy, ubiquitination, endocytosis, and glycolysis. Three modules strongly associated with the apolipoprotein E ε4 ( ε4) AD risk genotype mapped to oxidant detoxification, mitogen-associated protein kinase signaling, neddylation, and mitochondrial biology and overlapped with a previously described lipoprotein module in serum. Alterations of all three modules in blood were associated with dementia more than 20 years before diagnosis. Analysis of CSF samples from an AD phase 2 clinical trial of atomoxetine (ATX) demonstrated that abnormal elevations in the glycolysis CSF module-the network module most strongly correlated to cognitive function-were reduced by ATX treatment. Clustering of individuals based on their CSF proteomic profiles revealed heterogeneity of pathological changes not fully reflected by Aβ and tau.
Topics: Humans; Alzheimer Disease; Proteomics; Apolipoprotein E4; Atomoxetine Hydrochloride; tau Proteins; Amyloid beta-Peptides; Male; Aged; Female; Biomarkers
PubMed: 38924431
DOI: 10.1126/scitranslmed.adn3504 -
Journal of Diabetes Jul 2024Cardiovascular disease (CVD) is recognized as a primary and severe comorbidity in patients with type 2 diabetes mellitus (T2DM) and is also identified as a leading cause...
BACKGROUND
Cardiovascular disease (CVD) is recognized as a primary and severe comorbidity in patients with type 2 diabetes mellitus (T2DM) and is also identified as a leading cause of mortality within this population. Consequently, the identification of novel biomarkers for the risk stratification and progression of CVD in individuals with T2DM is of critical importance.
METHODS
This retrospective cohort study encompassed 979 patients diagnosed with T2DM, of whom 116 experienced CVD events during the follow-up period. Clinical assessments and comprehensive blood laboratory analyses were conducted. Age- and sex-adjusted Cox proportional hazard regression analysis was utilized to evaluate the association between lipoprotein-associated phospholipase A (Lp-PLA), C1q/tumor necrosis factor-related protein 3 (CTRP-3), and the incidence of CVD in T2DM. The diagnostic performance of these biomarkers was assessed through receiver operating characteristic (ROC) curve analysis and the computation of the area under the curve (AUC).
RESULTS
Over a median follow-up of 84 months (interquartile range: 42 [32-54] months), both novel inflammatory markers, Lp-PLA and CTRP-3, and traditional lipid indices, such as low-density lipoprotein cholesterol and apolipoprotein B, exhibited aberrant expression in the CVD-afflicted subset of the T2DM cohort. Age- and sex-adjusted Cox regression analysis delineated that Lp-PLA (hazard ratio [HR] = 1.007 [95% confidence interval {CI}: 1.005-1.009], p < 0.001) and CTRP-3 (HR = 0.943 [95% CI: 0.935-0.954], p < 0.001) were independently associated with the manifestation of CVD in T2DM. ROC curve analysis indicated a substantial predictive capacity for Lp-PLA (AUC = 0.81 [95% CI: 0.77-0.85], p < 0.001) and CTRP-3 (AUC = 0.91 [95% CI: 0.89-0.93], p < 0.001) in forecasting CVD occurrence in T2DM. The combined biomarker approach yielded an AUC of 0.94 (95% CI: 0.93-0.96), p < 0.001, indicating enhanced diagnostic accuracy.
CONCLUSIONS
The findings suggest that the biomarkers Lp-PLA and CTRP-3 are dysregulated in patients with T2DM who develop CVD and that each biomarker is independently associated with the occurrence of CVD. The combined assessment of Lp-PLA and CTRP-3 may significantly augment the diagnostic precision for CVD in the T2DM demographic.
Topics: Humans; Diabetes Mellitus, Type 2; Male; Female; Biomarkers; Middle Aged; Cardiovascular Diseases; 1-Alkyl-2-acetylglycerophosphocholine Esterase; Retrospective Studies; Aged; Follow-Up Studies; ROC Curve; Risk Factors
PubMed: 38924255
DOI: 10.1111/1753-0407.13574 -
Pathogens (Basel, Switzerland) Jun 2024This study investigates the impact of Epstein-Barr virus (EBV) infection on children's proteomes across different phases of the disease, utilising seventy-nine blood...
This study investigates the impact of Epstein-Barr virus (EBV) infection on children's proteomes across different phases of the disease, utilising seventy-nine blood samples categorised into three groups: EBV-naive patients, acute infectious mononucleosis (IM) cases, and convalescents followed up for 12 months post-IM. The aim is to identify proteins influenced by EBV infection, shedding light on the chronic processes triggered by the virus. The results reveal thirty-nine proteins distinguishing between naive patients and those with IM, including actin, lumican, peroxiredoxin-2, fibulin-1, gelsolin, and alpha-2-macroglobulin, which are involved in immune responses, cell adhesion, and inflammation. Elevated oxidative stress markers like peroxiredoxin-2 in IM patients suggest potential links to EBV's induction of reactive oxygen species. Increased levels of apolipoproteins A-I, A-IV, C-IV, and M during IM imply associations with viral infection, while complement system proteins (C1q, C1r, and C8 gamma chain) are also elevated, reflecting their role in the immune response and viral clearance. This study's focus on children provides unique insights into EBV's impact on young populations, emphasising proteomics' role in uncovering protein associations and understanding the virus's long-term consequences. However, specific relationships between identified proteins and EBV infection require further investigation.
PubMed: 38921769
DOI: 10.3390/pathogens13060471 -
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