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Biomarker Insights 2024Colorectal cancer (CRC) prognosis is determined by the disease stage with low survival rates for advanced stages. Current CRC screening programs are mainly using...
BACKGROUND
Colorectal cancer (CRC) prognosis is determined by the disease stage with low survival rates for advanced stages. Current CRC screening programs are mainly using colonoscopy, limited by its invasiveness and high cost. Therefore, non-invasive, cost-effective, and accurate alternatives are urgently needed.
OBJECTIVE AND DESIGN
This retrospective multi-center plasma proteomics study was performed to identify potential blood-based biomarkers in 36 CRC patients and 26 healthy volunteers by high-resolution mass spectrometry proteomics followed by the validation in an independent CRC cohort (60 CRC patients and 44 healthy subjects) of identified selected biomarkers.
RESULTS
Among the 322 identified plasma proteins, 37 were changed between CRC patients and healthy volunteers and were associated with the complement cascade, cholesterol metabolism, and SERPIN family members. Increased levels in CRC patients of the complement proteins C1QB, C4B, and C5 as well as pro-inflammatory proteins, lipopolysaccharide-binding protein (LBP) and serum amyloid A4, constitutive (SAA4) were revealed for first time. Importantly, increased level of C5 was verified in an independent validation CRC cohort. Increased C4B and C8A levels were correlated with cancer-associated inflammation and CRC progression, while cancer-associated inflammation was linked to the acute-phase reactant leucine-rich alpha-2-glycoprotein 1 (LRG1) and ceruloplasmin. Moreover, a 4-protein signature including C4B, C8A, apolipoprotein C2 (APO) C2, and immunoglobulin heavy constant gamma 2 was changed between early and late CRC stages.
CONCLUSION
Our results suggest that C5 could be a potential biomarker for CRC diagnosis. Further validation studies will aid the application of these new potential biomarkers to improve CRC diagnosis and patient care.
PubMed: 38911905
DOI: 10.1177/11772719241257739 -
EBioMedicine Jun 2024Mapping gut microecological features to serum metabolites (SMs) will help identify functional links between gut microbiome and cardiometabolic health.
BACKGROUND
Mapping gut microecological features to serum metabolites (SMs) will help identify functional links between gut microbiome and cardiometabolic health.
METHODS
This study encompassed 836-1021 adults over 9.7 year in a cohort, assessing metabolic syndrome (MS), carotid atherosclerotic plaque (CAP), and other metadata triennially. We analyzed mid-term microbial metagenomics, targeted fecal and serum metabolomics, host genetics, and serum proteomics.
FINDINGS
Gut microbiota and metabolites (GMM) accounted for 15.1% overall variance in 168 SMs, with individual GMM factors explaining 5.65%-10.1%, host genetics 3.23%, and sociodemographic factors 5.95%. Specifically, GMM elucidated 5.5%-49.6% variance in the top 32 GMM-explained SMs. Each 20% increase in the 32 metabolite score (derived from the 32 SMs) correlated with 73% (95% confidence interval [CI]: 53%-95%) and 19% (95% CI: 11%-27%) increases in MS and CAP incidences, respectively. Among the 32 GMM-explained SMs, sebacic acid, indoleacetic acid, and eicosapentaenoic acid were linked to MS or CAP incidence. Serum proteomics revealed certain proteins, particularly the apolipoprotein family, mediated the relationship between GMM-SMs and cardiometabolic risks.
INTERPRETATION
This study reveals the significant influence of GMM on SM profiles and illustrates the intricate connections between GMM-explained SMs, serum proteins, and the incidence of MS and CAP, providing insights into the roles of gut dysbiosis in cardiometabolic health via regulating blood metabolites.
FUNDING
This study was jointly supported by the National Natural Science Foundation of China, Key Research and Development Program of Guangzhou, 5010 Program for Clinical Research of Sun Yat-sen University, and the 'Pioneer' and 'Leading goose' R&D Program of Zhejiang.
PubMed: 38908099
DOI: 10.1016/j.ebiom.2024.105209 -
Life Science Alliance Sep 2024Apolipoprotein E4, the most important genetic risk factor for Alzheimer's disease, is shown to internalize into neurons and intersect with amyloid-β in...
Apolipoprotein E4, the most important genetic risk factor for Alzheimer's disease, is shown to internalize into neurons and intersect with amyloid-β in endosomes-autophagosomes of neurites and modulate intraneuronal amyloid-β-42.
PubMed: 38906679
DOI: 10.26508/lsa.202402875 -
Environment International Jun 2024Emerging evidence has linked arsenic exposure and metabolic homeostasis, but the mechanism is incompletely understood, especially at relatively low concentrations. In...
Emerging evidence has linked arsenic exposure and metabolic homeostasis, but the mechanism is incompletely understood, especially at relatively low concentrations. In this study, we used a mouse model to evaluate the health impacts and metabolic toxicity of arsenic exposure in drinking water at environmentally relevant levels (0.25 and 1.0 ppm). Our results indicated that arsenic damaged intestinal barrier and induced arsenic accumulation, oxidative stress, and pathological changes in the liver and illum. Interestingly, arsenic increased the hepatic triglyceride (TG) and total cholesterol (TC), while reduced serum TG and TC levels. The liver transcriptome found that arsenic exposure caused transcriptome perturbation and promoted hepatic lipid accumulation by regulating the exogenous fatty acids degradation and apolipoproteins related genes. The serum metabolomics identified 74 and 88 differential metabolites in 0.25 and 1.0 ppm, respectively. The KEGG disease and subcellular location analysis indicated that arsenic induced liver and intestinal diseases, and the mitochondrion might be the target organelle for arsenic-induced toxicity. Co-enrichment of transcriptome and metabolome identified 24 metabolites and 9 genes as metabolic toxicity biomarkers. Moreover, 40 male (20 nonalcoholic fatty liver disease (NAFLD) cases and 20 healthy controls) was further selected to validate our findings. Importantly, the significantly changed L-palmitoylcarnitine, 3-hydroxybutyric acid, 2-hydroxycaproic acid and 6 genes of Hadha, Acadl, Aldh3a2, Cpt1a, Cpt2, and Acox1 were found in the NAFLD cases. The results from integrated multi-omics and chemical-protein network analysis indicated that L-palmitoylcarnitine played a critical role in metabolic toxicity by regulating mitochondrial fatty acids β-oxidation genes (Cpt1a, Cpt2). In conclusion, these findings provided new clues for the metabolic toxicity of arsenic exposure at environmentally relevant levels, which involved in the late-life NAFLD development. Our results also contribute to understanding the human responses and phenotypic changes to this hazardous material exposure in the environment.
PubMed: 38906090
DOI: 10.1016/j.envint.2024.108819 -
Alternative Therapies in Health and... Jun 2024To evaluate the impact of differential emergency treatment measures on the prognosis of patients with ACS.
OBJECTIVE
To evaluate the impact of differential emergency treatment measures on the prognosis of patients with ACS.
METHODS
76 patients with ACS treated in the emergency department of our hospital from January 2017 to September 2021 were selected as the research objects. According to their main symptoms, general signs, and various examination results when arriving at the hospital, differential emergency treatment measures were implemented, so as to ensure the curative effect.
RESULT
After comprehensive emergency treatment, the venous blood test indicators of patients, including creatinine (CR), uric acid (UA), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein A (LPA), Apolipoprotein AI (ApoAI), Apolipoprotein B (ApoB), Potassium ion (K+), glucose (GLU), Cardiac troponin I (cTn) returned to normal. In addition, the proportion of patients without cardiogenic shock, ventricular fibrillation, respiratory and cardiac arrest, cerebral infarction, cerebral hemorrhage, arrhythmia, heart rupture, and other adverse reactions are as high as 92% (70/76).
CONCLUSION
For patients with ACS, it is necessary to take correct emergency rescue and treatment measures immediately, especially to actively implement the percutaneous coronary intervention (PCI) method, so as to give full play to the safety and effectiveness of emergency treatment and curb the possibility of patient death as much as possible.
PubMed: 38904625
DOI: No ID Found -
Health Science Reports Jun 2024This article explores the association between fractures, particularly in the elderly, and elevated plasma high-density lipoprotein cholesterol (HDL-C) levels. The study...
BACKGROUND
This article explores the association between fractures, particularly in the elderly, and elevated plasma high-density lipoprotein cholesterol (HDL-C) levels. The study challenges the conventional idea of HDL-C as "good cholesterol" by revealing its potential role as a risk factor for fractures. Factors contributing to fractures in the elderly, such as diminishing bone strength due to aging-related tissue breakdown, are discussed. Sedentary lifestyles, low bone mineral density (BMD), and habits like smoking and alcohol consumption compound fracture susceptibility.
MATERIALS AND METHODS
The study delves into mechanisms linking elevated HDL-C to fractures, using data from the ASPREE-Fracturesub-study of the ASPREE trial involving Australian and American participants aged 65 and above.
RESULTS
The study showed that over a 4-year period, elevated HDL-C levels in healthy older people were linked to a 14% higher fracture risk. This revelation expands the understanding of fracture risk factors beyond the established norms.
CONCLUSION
The article emphasizes the need to reconsider HDL-C's traditional role as an indicator of cardiovascular health, particularly in light of medications like Statins and Anacetrapib that raise HDL-C levels. It calls for further exploration into the relationship between HDL-C, fractures at varying sites, and different age groups. Practical implications involve incorporating fracture risk associated with high HDL-C into clinical considerations, alongside advocating lifestyle changes for optimal HDL-C levels. In summary, this study prompts a reevaluation of HDL-C's implications in clinical practice, demanding further investigation into the intricacies of this relationship.
PubMed: 38903661
DOI: 10.1002/hsr2.2187 -
Cureus May 2024Background The study aims to assess the association of apolipoprotein E (APOE) gene polymorphisms with serological lipid and inflammatory markers to determine their...
Background The study aims to assess the association of apolipoprotein E (APOE) gene polymorphisms with serological lipid and inflammatory markers to determine their potential role in predicting the risk of cardiovascular diseases (CVDs) and Alzheimer's disease (AD). Methodology A total of 915 individuals underwent testing for lipid and inflammatory biomarkers at Vibrant America Clinical Laboratory. Clinical data, blood lipid and inflammatory profiles, and APOE genotyping were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results Compared to the E3/E3 genotype, individuals with E2/E3 genotypes showed higher levels of high-density lipoprotein (HDL), triglycerides, apolipoprotein A (APOA), high-sensitivity C-reactive protein (hs-CRP), and myeloperoxidase (MPO). E2/E4 genotype carriers had higher levels of HDL, triglycerides, Lp(a), and N-terminal pro b-type natriuretic peptide (BNPNT). E3/E4 genotypes were associated with elevated levels of total cholesterol, LDL, Lp(a), hs-CRP, small-density low-density lipoprotein (SDLDL), oxidized LDL (OXLDL), MPO, LDL-CAL, PLAC, and APOB. The E4/E4 group displayed higher concentrations of total cholesterol, LDL, APOB, Lp(a), hs-CRP, SDLDL, OXLDL, MPO, LDLCAL, and PLAC compared to E3/E3 carriers. These findings highlight the potential atherogenic effect of the ε4 allele and the protective effect of the ε2 allele based on lipid and inflammatory marker profiles. Conclusions This study provides strong evidence linking APOE gene polymorphism to abnormal serum lipid and inflammatory profiles. Individuals carrying the ε4 alleles exhibited dysregulated lipid metabolism and abnormal inflammatory markers, increasing their risk of CVD and AD. Early detection and prompt diagnosis are crucial for implementing therapeutic, dietary, and lifestyle interventions to mitigate risks and prevent or delay lipid and inflammation-related disorders.
PubMed: 38903305
DOI: 10.7759/cureus.60721 -
Frontiers in Neuroanatomy 2024Literature suggests a common pathophysiological ground between carotid atherosclerosis (CAS) and white matter alterations in the brain. However, the association between...
INTRODUCTION
Literature suggests a common pathophysiological ground between carotid atherosclerosis (CAS) and white matter alterations in the brain. However, the association between carotid intima-media thickness (CIMT) and white matter hyperintensities (WMH) has not been conclusively reported. The current systematic review explores and reports the relationship between CIMT and WMH among asymptomatic/non-stroke adults.
METHODS
A recent literature search on PubMed, SCOPUS, and Web of Science databases was conducted in compliance with the PRISMA protocol. The pre-defined Population-Intervention-Comparison-Outcome-Study (PICOS) criteria included observational studies investigating the CIMT-WMH association among non-stroke adults undergoing magnetic resonance imaging and carotid ultrasound.
RESULTS
Out of 255 potential results, 32 studies were critically assessed for selection, and finally, 10 articles were included, comprising 5,116 patients (females = 60.2%; males = 39.8%) aged between 36-71 years. The included studies earned high quality ratings (6-9) based on the Newcastle-Ottawa-Scale criteria. Qualitative synthesis showed a significantly parallel relationship between increased CIMT and greater WMH burden in 50% of the studies. In addition, significant risk factors related to the CIMT-WMH association included older age, hypertension, depression, migraine, Hispanic ethnicity, and apolipoprotein E (ɛ4) in postmenopausal women.
CONCLUSION
Overall, the cumulative evidence showed a consistent CIMT-WMH association in asymptomatic middle-aged and older non-stroke adults, indicating that CAS may contribute to the progression of pathologically hyperintense white matter in the brain. However, further research is warranted to infer the plausible relationship between CIMT and WMH in the absence of stroke.
PubMed: 38903057
DOI: 10.3389/fnana.2024.1394766 -
Circulation Journal : Official Journal... Jun 2024Because apolipoprotein-A2 (ApoA2), a key component of high-density lipoprotein cholesterol (HDL-C), lacks clear clinical significance, we investigated its impact on...
BACKGROUND
Because apolipoprotein-A2 (ApoA2), a key component of high-density lipoprotein cholesterol (HDL-C), lacks clear clinical significance, we investigated its impact on cardiovascular events in patients undergoing percutaneous coronary intervention (PCI).Methods and Results: We examined 638 patients who underwent PCI with a new-generation drug-eluting stent for acute or chronic coronary syndrome and had their apolipoprotein levels measured between 2016 and 2021. The patients were divided into 2 groups based on the median serum ApoA2 values, and the incidence of major adverse cardiovascular events (MACE) was assessed. Of the 638 patients, 563 (88%) received statin treatment, with a median serum LDL-C level of 93 mg/dL. Furthermore, 137 patients (21.5%) experienced MACE, and Kaplan-Meier analysis revealed that the higher ApoA2 group had a significantly lower incidence of MACE than the lower ApoA2 group (30.9% vs. 41.6%). However, the other apolipoproteins, including ApoA1, ApoB, ApoC2, ApoC3, and ApoE, showed no significant differences in MACE. Multivariable Cox hazard analysis indicated that ApoA2 was an independent predictor of MACEs (hazard ratio, 0.666; 95% confidence interval, 0.465-0.954). Furthermore, ApoA2 levels exhibited the strongest inverse association with high-sensitivity C-reactive protein levels (r=-0.479).
CONCLUSIONS
Among all the apolipoproteins, the serum ApoA2 level may be the strongest predictor of future cardiovascular events and prognosis in patients undergoing PCI.
PubMed: 38897974
DOI: 10.1253/circj.CJ-24-0242 -
Bioscience Reports Jun 2024Lipoprotein(a) (Lp(a)) is a low-density lipoprotein (LDL)-like particle in which the apolipoprotein B component is covalently linked to apolipoprotein(a). Lp(a) is a...
Lipoprotein(a) (Lp(a)) is a low-density lipoprotein (LDL)-like particle in which the apolipoprotein B component is covalently linked to apolipoprotein(a). Lp(a) is a well-established independent risk factor for cardiovascular diseases. Plasma lipoprotein(a) concentrations vary enormously between individuals and ethnic groups. Several nucleotide polymorphisms in the SLC22A3 gene associate with Lp(a) concentration in people of different ethnicities. We investigated the association of a Polynesian-specific (Māori and Pacific peoples) SLC22A3 gene coding variant p.Thr44Met) with the plasma concentration of Lp(a) in a cohort of 302 healthy Polynesian males. An apolipoprotein(a)-size independent assay assessed plasma lipoprotein(a) concentrations, all other lipid and apolipoprotein concentrations were measured using standard laboratory techniques. Quantitative real-time polymerase chain reaction was used to determine apolipoprotein(a) isoforms. The range of metabolic (HbA1c, blood pressure and blood lipids) and blood lipid variables were similar between the non-carriers and carriers in age, ethnicity and BMI adjusted models. However, rs8187715 SLC22A3 variant was significantly associated with lower lipoprotein(a) concentrations. Median lipoprotein(a) concentration was 10.60 nmol/L (IQR 5.40 to 41.00) in non-carrier group, and was 7.60 nmol/L (IQR 5.50 to 12.10) in variant carrier group (p <0.05). Lp(a) concentration inversely correlated with apolipoprotein(a) isoform size. After correction for apolipoprotein(a) isoform size, metabolic parameters and ethnicity, the association between the SLC22A3 variant and plasma Lp(a) concentration remained. This study is the first to identify the association of this gene variant and low plasma Lp(a) concentrations. This provides evidence for better guidance on ethnic specific cut-offs when defining "elevated" and "normal" plasma Lp(a) concentrations in clinical applications.
PubMed: 38896441
DOI: 10.1042/BSR20240403