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PubMed2006

C-reactive protein levels in subjects with Prader-Willi syndrome and obesity.

PURPOSE: Prader-Willi syndrome is characterized by infantile hypotonia, feeding difficulties, hypogonadism, small hands and feet, mental deficiency, behavioral problems, and hyperphagia leading to obesity in early childhood. To date there have been no studies examining the associated risk of cardiovascular disease related to obesity in Prader-Willi syndrome, nor of circulating biomarkers such as C-reactive protein known to be predictive of cardiovascular disease. Therefore, we have measured the levels of C-reactive protein in a descriptive study of a cohort of Prader-Willi syndrome and comparison subjects. METHODS: An immunoassay was used to quantify C-reactive protein in plasma samples from subjects with Prader-Willi syndrome and obesity and compared to anthropometric and body composition data. RESULTS: The mean circulating C-reactive protein concentration for 28 subjects with Prader-Willi syndrome (13 females, 15 males; mean age 24.6 +/- 11.6 years; mean body mass index 35.9 +/- 11.9) was 10.3 +/- 8.8 mg/L. The mean C-reactive protein concentration for 22 nonsyndromic obese subjects (16 females, 6 males; mean age 32.3 +/- 12.2 years; mean body mass index 36.6 +/- 10.7) was 8.8 +/- 10.9 mg/L. The reported mean value for C-reactive protein was 2.6 +/- 3.0 mg/L from 100 healthy adults. CONCLUSIONS: The mean C-reactive protein values were similar between the subjects with Prader-Willi syndrome and obesity but significantly higher in Prader-Willi syndrome and obese subjects relative to normative data. Increased levels of C-reactive protein (>3.0 mg/L) are associated with cardiovascular disease suggesting subjects with Prader-Willi syndrome as well as obese subjects are at a similar increased risk.

Adolescent↗

PubMed2026

AgRP reflects glucocorticoid action: integrated experimental and clinical evidence.

PURPOSE: Glucocorticoids (GCs) are key regulators of energy homeostasis. Clinically, patients with Cushing's syndrome exhibit obesity, whereas adrenal insufficiency is associated with weight loss. However, circulating biomarkers reflecting GC action have not been established. Agouti-related protein (AgRP), an orexigenic neuropeptide, is upregulated by GC in the rodent hypothalamus. Here, we investigated whether AgRP is a surrogate marker of GC action through in vitro and in vivo experiments as well as a clinical study. METHODS: The GC-dependent transcriptional regulation of AgRP was examined using reporter assays in neuronal BE(2)C cells. In animal experiments, the effects of GC on hypothalamic AgRP mRNA expression in C57BL/6J mice were examined. Circulating AgRP levels were also analyzed in nine patients with adrenal Cushing's syndrome before and after surgery. RESULTS: Two functional glucocorticoid-responsive elements (GREs) were identified in the human AgRP gene promoter, through which GC enhanced AgRP transcriptional activity. In mice, corticosterone (CORT) administration induced hyperphagia and increased hypothalamic AgRP mRNA levels, which positively correlated with plasma CORT levels. In patients with adrenal Cushing's syndrome, circulating AgRP levels significantly decreased after surgery (118.7 ± 40.3 vs. 37.7 ± 9.5 pg/mL, p < 0.01) and positively correlated with serum cortisol levels (r = 0.79, p < 0.01). CONCLUSION: These findings demonstrate that GC positively regulates AgRP across molecular, animal, and clinical settings, supporting the hypothesis that circulating AgRP may serve as a surrogate indicator of GC action. Further studies are warranted to establish its clinical applicability.

Animals↗

PubMed2006

Adipocyte fatty acid-binding protein is a plasma biomarker closely associated with obesity and metabolic syndrome.

BACKGROUND: Adipocyte fatty acid-binding protein (A-FABP) is traditionally thought to be a cytosolic fatty acid chaperone expressed in adipocytes. Mice with targeted disruption of the A-FABP gene exhibit a striking phenotype with strong protection from insulin resistance, hyperglycemia, and atherosclerosis. The clinical relevance of these findings remains to be confirmed. METHODS: We used tandem mass spectrometry-based proteomic analysis to identify proteins secreted from adipocytes and present in human serum. We measured serum A-FABP concentrations in 229 persons (121 men and 108 women; age range, 33-72 years), including 100 lean [body mass index (BMI) <25 kg/m2] and 129 overweight/obese individuals (BMI >25 kg/m2) selected from a previous cross-sectional study. RESULTS: A-FABP was released from adipocytes and was abundantly present in human serum. Mean (SD) circulating concentrations of A-FABP were significantly higher in overweight/obese than in lean persons [32.3 (14.8) vs 20.0 (9.8) microg/L; P < 0.001]. Age- and sex-adjusted serum A-FABP concentrations correlated positively (P < 0.005) with waist circumference, blood pressure, dyslipidemia, fasting insulin, and the homeostasis model assessment insulin resistance index. Moreover, we observed a significant increase in A-FABP concentrations corresponding with increases in the number of components of the metabolic syndrome (P < 0.05). CONCLUSIONS: A-FABP is a circulating biomarker closely associated with obesity and components of the metabolic syndrome, and measurement of serum concentrations of A-FABP might be useful for clinical diagnosis of obesity-related metabolic and cardiovascular disorders.

Adipocytes↗

PubMed2006

Relationships between biomarkers of exposure and toxicokinetics in Fischer 344 rats and B6C3F1 mice administered single doses of acrylamide and glycidamide and multiple doses of acrylamide.

Acrylamide (AA) is a widely studied industrial chemical that is neurotoxic, mutagenic to somatic and germ cells and carcinogenic in rodents. AA is also formed in many commonly consumed starchy foods during cooking. Our previous toxicokinetic investigations of AA and its important genotoxic metabolite, glycidamide (GA), in rodents showed that AA is highly bioavailable from oral routes of administration, is widely distributed to tissues and that the dietary route, in particular, favors metabolism to GA. Measurements of DNA adducts in many tissues supported the hypothesis that AA is carcinogenic in rodent bioassays through metabolism to GA. The current investigation describes the development and validation of methodology for measuring hemoglobin (Hb) adducts with AA and GA in the same rodents previously used for toxicokinetic and DNA adduct measurements. The goal was to investigate possible relationships between these circulating biomarkers of exposure and serum toxicokinetic parameters for AA and GA and tissue GA-DNA adducts in rodents from both single and repeated dosing with AA. Significant correlations were observed between GA-Hb and liver GA-DNA adducts for either single or multiple dosing regimens with AA. Using available GA-Hb adduct data, empirical and allometric relationships permitted estimation of liver DNA adducts in humans in the range of 0.06-0.3 adducts/10(8) nucleotides. This approach may prove useful in extrapolating human cancer risks from findings in rodent bioassays.

Acrylamide↗

PubMed2006

Noninvasive detection of subclinical coronary atherosclerosis coupled with assessment of changes in plaque characteristics using novel invasive imaging modalities: the Integrated Biomarker and Imaging Study (IBIS).

OBJECTIVES: Our purpose was to assess noninvasive imaging in detection of subclinical atherosclerosis and to examine novel invasive modalities to describe prevalence and temporal changes in putative characteristics of "high-risk" plaques. BACKGROUND: Conventional coronary imaging cannot identify "high-risk" lesions. METHODS: Conventional (quantitative angiography and intravascular ultrasound [IVUS]) and novel imaging (IVUS-based palpography and gray scale echogenicity) were performed at baseline and 6 months later in 67 patients with diverse clinical presentations. Different imaging techniques were compared within a common segment defined by multislice computed tomography (MSCT). RESULTS: Compared with IVUS, the sensitivity, specificity, and positive and negative predictive value of MSCT for detecting significant plaque was 86%, 69%, 90%, and 61%, respectively. In coronary arteries with <50% stenosis, there were no temporal changes in luminal and plaque dimensions measured by quantitative coronary angiography or IVUS; however, a significant reduction in abnormal strain pattern was detected on palpography (density high strain spots/cm: 1.6 +/- 1.5 vs. 1.2 +/- 1.4, p = 0.0123. These changes were mainly related to significant changes in patients who presented with ST-segment elevation myocardial infarction. The assessment of plaque echogenicity showed no temporal changes. There were no correlations between circulating biomarkers and quantifiable imaging parameters. CONCLUSIONS: Mild angiographic disease is associated with large atherosclerotic plaques on MSCT. Conventional invasive coronary imaging reveals static luminal and plaque dimensions on standard medical therapy with plaque hypoechogenicity remaining unchanged over the 6-month period. By contrast, palpography measurements of strain correlate with clinical presentation and significantly decrease on standard medical therapy. Novel imaging modalities, such as palpography, might provide insights into plaque biology and might eventually serve as intermediate end points in interventional trials.

Coronary Angiography↗

PubMed2002

[Treatment monitoring, recurrence detection, prognosis. Here's where tumor markers make good sense].

Of the growing group of cancer biomarkers, circulating humoral tumour markers (TM) are the longest-known subgroup of substances with protein, lipid, glycolipid or carbohydrate structure, that can be used as probes for identifying the origin, growth and therapy-related debulking of a tumor. Relevant TM are well-defined and easy to determine, and disturbing factors and statistical characteristics well-known. They are most commonly used not so much for early detection, localization and diagnosis, but for treatment monitoring, detection of recurrence and, latterly, also for outcome prediction. Their particular value lies in their supporting role in invasive imaging or endoscopic procedures. In some cases, they may also prolong the intervals between for such procedures.

Biomarkers, Tumor↗

PubMed2026

Epigenetic and Transcriptional Regulatory Networks Underlying Psoriasis Pathogenesis.

Psoriasis is a chronic, immune-mediated dermatologic disorder characterized by the hyperproliferation of keratinocytes and dysregulated immune signaling. Although genome-wide association studies have identified susceptibility loci, the multifactorial nature of the disease underlines the importance of nongenetic regulatory mechanisms. Among these epigenetic modifications are those that critically link genetic predisposition with environmental stimuli. This review offers an in-depth overview of the current insights into the role of epigenetic regulation in the pathophysiology of psoriasis. Key mechanisms, including aberrant DNA methylation, histone post-translational modifications (eg, H3K27ac, H3K4me3), and dysregulated noncoding RNAs, are discussed in the context of inflammatory signaling and immune cell function. This review also explores how environmental factors such as UV radiation and air pollution induce the epigenetic reprogramming that perpetuates the proinflammatory state. Furthermore, it highlights the translational potential of targeting epigenetic regulators and epigenome-editing technologies, including clustered regularly interspaced short palindromic repeats (CRISPR) fusion systems, as precision therapeutic strategies. In parallel, advances in single-cell epigenomics, spatial transcriptomics, and the profiling of circulating biomarkers offer novel diagnostic tools. Despite advances, challenges persist, including the limited predictive value of preclinical models and variable epigenetic profiles. Positioning epigenetics as the bridge between genetic risk, environmental triggers, and therapeutic advances, this review presents a framework for precision medicine in psoriasis.

Humans↗

PubMed2006

The Genetics of Generalized Osteoarthritis (GOGO) study: study design and evaluation of osteoarthritis phenotypes.

PURPOSE: The primary goal of the Genetics of Generalized Osteoarthritis (GOGO) study is to identify chromosomal regions associated with increased susceptibility to generalized osteoarthritis (OA). Here we describe the study design and phenotype of the 2728 participants from the 1145 families recruited for this study. METHODS: GOGO is an investigator-initiated collaboration involving seven clinical academic sites and sponsored by GlaxoSmithKline. Family ascertainment was carried out between 1999 and 2002. A qualifying family required self-reported Caucasian ethnicity and at least two affected siblings with clinical hand OA. We hypothesized that this clinical phenotype would facilitate identification of participants with multijoint radiographic OA (rOA) in and beyond the hand. The "gold standard" case definition, however, was based on rOA (Kellgren-Lawrence grade > or =2) involving > or =3 hand joints distributed bilaterally and including at least one distal interphalangeal joint, with two of the three involved joints within a joint group (distal interphalangeal, proximal interphalangeal, or carpometacarpal). Radiographs of hips, knees and spine were also obtained. Additional siblings and living parents from qualifying families, both affected and unaffected, were invited to participate. RESULTS: A total of 2706 participants had complete clinical and radiological examination data. Of these, 2569 participants met clinical examination criteria for affected status; while 1963 (73%) participants met the prespecified radiographic criteria for affected status. This corresponded to a total of 707 families with at least two affected siblings that met the hand rOA criteria. Of those individuals with rOA of the hand, the frequency of rOA at other sites was highest for the knee (51%) and spine (54%), and less common for the hip (25%). Concordance rates among hand affected siblings were greatest for spine (36%) followed by knee (31%) and hip (9%); a total of 53% of the affected sib pairs were concordant for specific patterns of generalized rOA involving the hand and large joints (knees, hips or spine). CONCLUSIONS: GOGO represents a large multicenter collection of families with multiple joint OA that have been characterized both clinically and radiographically. The GOGO study will employ a comprehensive strategy for genetic screening based upon both qualitative and quantitative radiographic trait analyses, circulating biomarkers in a quantitative trait-based analysis, fine mapping, and candidate gene analysis. This sample should provide sufficient power to detect linkage to OA associated genes.

Adult↗

PubMed2026

Fatty acids and breast cancer: Epidemiology, subtype-specific metabolism, immune regulation, and clinical translation.

Fatty acids (FAs) are bioactive dietary and metabolic molecules that participate in membrane architecture, energy homeostasis, inflammatory signaling, gene regulation and immune function, all of which intersect with breast cancer (BC) risk, progression and treatment response. In this narrative review we integrate epidemiological, clinical, translational and mechanistic evidence on the role of FAs in BC. Saturated, monounsaturated, trans- and polyunsaturated FAs (PUFAs) are treated as distinct biological exposures rather than interchangeable measures of total fat intake. Similarly, evidence from dietary assessment, circulating biomarkers, erythrocyte membrane composition, adipose tissue stores and tumor lipid signatures is interpreted separately, because each captures exposure and biology at a different level. BC subtypes differ in FA synthesis, uptake, oxidation, storage and remodeling: luminal tumors are frequently linked to hormone-regulated lipogenesis, human epidermal growth factor receptor 2 (HER2)-positive tumors to growth-factor-driven lipid metabolism, and triple-negative tumors to exogenous FA uptake, inflammatory lipid mediators and ferroptosis-related vulnerabilities. FA-derived mediators also shape immune-cell polarization, cytokine signaling and the tumor microenvironment, and dietary FAs may reshape the gut microbiota; the fiber-derived short-chain FAs it produces, distinct from dietary FAs, likewise help regulate immune and inflammatory tone. Clinical data suggest possible roles for fat-quality modification and selected n-3 PUFA interventions, but findings are heterogeneous and not yet sufficient to support routine biomarker-guided precision onco-nutrition. Candidate biomarkers, such as erythrocyte n-6:n-3 composition, require prospective validation before clinical implementation. FA biology thus represents a modifiable but complex axis in BC prevention, tumor biology and supportive care.

Humans↗

PubMed2006

Urinary excretion of acrylamide and metabolites in Fischer 344 rats and B6C3F(1) mice administered a single dose of acrylamide.

Acrylamide (AA) is a widely studied industrial chemical that is neurotoxic, mutagenic to somatic and germ cells, and carcinogenic in mice and rats. AA is also formed during cooking in many commonly consumed starchy foods. Our previous toxicokinetic investigations of AA and its genotoxic metabolite, glycidamide (GA), in rodents showed that AA is highly bioavailable from oral routes of administration, is widely distributed to tissues, and that the dietary route, in particular, favors metabolism to GA. Formation and accumulation of mutagenic GA-DNA adducts in many tissues support the hypothesis that AA is carcinogenic in rodent bioassays through metabolism to GA. The current investigation describes the quantification of 24 h urinary metabolites, including free AA and GA and their mercapturic acid conjugates (AAMA and GAMA, respectively), using LC/MS/MS in F344 rats and B6C3F(1) mice following a dose of 0.1 mg/kg bw given by intravenous, gavage, and dietary routes of administration. Similar groups of rodents were used previously for serum/tissue toxicokinetic and adduct determinations (DNA and hemoglobin). The goal was to investigate relationships between urinary and circulating biomarkers of exposure, toxicokinetic parameters for AA and GA, and tissue GA-DNA adducts in rodents from single doses of AA. Significant linear correlations were observed between urinary levels of AA with AAMA and GA with GAMA in the current data sets for rats and mice. Concentrations of AA and AAMA correlated significantly with average AUC values determined previously for AA in groups of rats and mice similarly dosed with AA. Urinary GA and GAMA concentrations showed significant correlations with average AUC values for GA and liver GA-DNA adducts determined previously in rats and mice similarly dosed with AA. Despite statistical significance, considerable inter-animal variability was observed in all urinary measurements, which limited the degree of correlation with either average toxicokinetic or biomarker data collected from different groups of animals. These results suggest that urinary measurements of AA and its metabolites may be useful for prediction of internal exposures to AA and GA.

Acetylcysteine↗

PubMed2026

Adolescent depression as a systemic multimorbidity catalyst: integrated genetic and metabolic pathway analysis.

BACKGROUND: Although adolescent depression has been linked to individual chronic conditions, its broader role in shaping multimorbidity risk remains understudied. METHODS: A total of 87,562 UK Biobank participants were included, of whom 18,851 had documented adolescent depression. Cox proportional hazards models were applied to evaluate associations between adolescent depression and 24 chronic diseases, followed by stratified analyses by sex and age. Two-sample Mendelian randomization (MR) was then conducted to infer causality for diseases showing significant associations. Genomic colocalization analyses were performed using relevant GWAS data to identify shared causal variants. Mediation analyses were performed to detect possible mediating factors, including the frailty index, KDM biological age acceleration, allostatic load and 30 circulating biomarkers. RESULTS: Adolescent depression was associated with elevated risk for 12 chronic diseases, with strongest associations for hypothyroidism (HR = 1.29 [1.18-1.42]), diabetes (HR = 1.25 [1.13-1.38]) and chronic obstructive pulmonary disease (COPD) (HR = 1.74 [1.50-2.01]). Risks were notably higher among females and younger adults. MR confirmed likely causal relationships for hypothyroidism (OR = 1.45 [1.03-2.05]), diabetes (OR = 1.01 [1.01-1.02]) and COPD (OR = 1.04 [1.02-1.06]). Genomic colocalization revealed a shared genetic signal at the CDSN/PSORS1C1 locus between adolescent depression and hypothyroidism. Mediation analyses revealed disease-specific pathways: creatinine for hypothyroidism, testosterone for diabetes, KDM biological ageing for COPD and frailty index across all three conditions. CONCLUSIONS: Adolescent depression confers systemic vulnerability through genetic and metabolic mechanisms, with amplified risks in females and individuals aged ≤55 years. These findings support early, integrated interventions to mitigate long-term multimorbidity.

Humans↗

PubMed2026

Integrative Analysis Uncover the Effects and Multi-Omics Features of Thigh Muscle Fat Infiltration.

The health impacts and underlying biological pathways of thigh muscle fat infiltration (TMFI) remain incompletely understood. In this study, we analyzed TMFI measured by magnetic resonance imaging in 55,120 UK Biobank participants and found that higher TMFI was significantly associated with all-cause mortality as well as with all major system-specific diseases examined (p values ranged from 2.50 × 10-88 to 9.97 × 10-04). TMFI also mediated the effects of lifestyle factors on health-related outcomes, with mediation proportions ranging from 6.7% to 71.7%. A genome-wide association study (GWAS) identified 79 lead single nucleotide polymorphisms (SNPs) linked to TMFI, and the polygenic risk score for TMFI was significantly associated with mortality and all incident diseases across examined organ systems in an independent subset of UK Biobank participants of European ancestry who were not included in the TMFI GWAS (n = 362,286, all p < 0.05). Gene-drug interactions identified multiple drugs that could potentially modulate TMFI. Analysis of single-cell transcriptomic data indicated that myogenic cells were strongly linked to TMFI (p = 7.08 × 10-08). Summary-data-based Mendelian randomization and Transcriptome-Wide Association Study analyses revealed numerous genes whose expression in specific tissues was associated with TMFI. Proteomic and metabolomic profiling uncovered a broad array of circulating biomarkers associated with TMFI, many of which mediated the effects of modifiable factors and genetic risk on TMFI. Overall, our results highlight the biological relevance of TMFI to human health and provide insights into the multi-omics mechanisms underlying TMFI, identifying potential targets for interventions.

Humans↗

PubMed2005

Future of early detection of lung cancer: the role of mouse models.

Early detection represents one of the most promising approaches to improving lung cancer survival. To date, no screening strategies have been shown to decrease mortality from the disease. Furthermore, no reliable circulating biomarkers of lung cancer have been identified that allow early diagnosis. With the advent of gene targeting technology, new genetically engineered mouse models of lung cancer closely recapitulate the pathobiology of human disease. These mouse models have enabled novel approaches to early detection, including the identification of cancer-associated serum markers using proteomic technologies and the development of new molecular imaging tools. The application of innovative technologies to accurate mouse models promises to accelerate the discovery of new molecular targets and imaging biomarkers for the early detection of lung cancer.

Animals↗

PubMed2003

Human epicardial adipose tissue is a source of inflammatory mediators.

BACKGROUND: Inflammatory mediators that originate in vascular and extravascular tissues promote coronary lesion formation. Adipose tissue may function as an endocrine organ that contributes to an inflammatory burden in patients at risk of cardiovascular complications. In this study, we sought to compare expression of inflammatory mediators in epicardial and subcutaneous adipose stores in patients with critical CAD. METHODS AND RESULTS: Paired samples of epicardial and subcutaneous adipose tissues were harvested at the outset of elective CABG surgery (n=42; age 65+/-10 years). Local expression of chemokine (monocyte chemotactic protein [MCP]-1) and inflammatory cytokines (interleukin [IL]-1beta, IL-6, and tumor necrosis factor [TNF]-alpha) was analyzed by TaqMan real-time reverse transcription-polymerase chain reaction (mRNA) and by ELISA (protein release over 3 hours). Significantly higher levels of IL-1beta, IL-6, MCP-1, and TNF-alpha mRNA and protein were observed in epicardial adipose stores. Proinflammatory properties of epicardial adipose tissue were noted irrespective of clinical variables (diabetes, body mass index, and chronic use of statins or ACE inhibitors/angiotensin II receptor blockers) or plasma concentrations of circulating biomarkers. In a subset of samples (n=11), global gene expression was explored by DNA microarray hybridization and confirmed the presence of a broad inflammatory reaction in epicardial adipose tissue in patients with coronary artery disease. The above findings were paralleled by the presence of inflammatory cell infiltrates in epicardial adipose stores. CONCLUSIONS: Epicardial adipose tissue is a source of several inflammatory mediators in high-risk cardiac patients. Plasma inflammatory biomarkers may not adequately reflect local tissue inflammation. Current therapies do not appear to eliminate local inflammatory signals in epicardial adipose tissue.

Adipose Tissue↗

PubMed2005

Comprehensive survey of common genetic variation at the plasminogen activator inhibitor-1 locus and relations to circulating plasminogen activator inhibitor-1 levels.

BACKGROUND: Using a linkage disequilibrium (LD)-based approach, we sought to comprehensively define common genetic variation at the plasminogen activator inhibitor-1 (PAI-1) locus and relate common single nucleotide polymorphisms (SNPs) and haplotypes to plasma PAI-1 levels. METHODS AND RESULTS: In reference pedigrees, we defined LD structure across a 50-kb genomic segment spanning the PAI-1 locus via a dense SNP map (1 SNP every 2 kb). Eighteen sequence variants that capture underlying common genetic variation were genotyped in 1328 unrelated Framingham Heart Study participants who had plasma PAI-1 antigen levels measured. Regression analyses were used to examine associations of individual SNPs and of inferred haplotypes with multivariable-adjusted PAI-1 levels. Two genetic variants, SNP rs2227631 and the 4G/5G polymorphism, were strongly associated (P<0.0001) with PAI-1 levels. SNP rs2227631 is in tight LD (D'=0.97, r2=0.78) with the 4G/5G polymorphism, which makes it difficult to distinguish which of these 2 polymorphisms is responsible for the association with PAI-1 levels. In stepwise analysis considering all polymorphisms tested, 3 SNPs, rs2227631 (or the correlated 4G/5G polymorphism), rs6465787, and rs2227674, each explained 2.5%, 1%, and 1%, respectively, of the residual variance in multivariable-adjusted PAI-1 levels (stepwise P<0.0001, P=0.04, and P=0.03, respectively). A single common haplotype, at 50% frequency among Framingham Heart Study participants, was strongly associated with higher PAI-1 levels (haplotype-specific P=0.00001). The susceptibility haplotype harbors the minor alleles of SNP rs2227631 and the 4G/5G polymorphism. CONCLUSIONS: Three sequence variants at the PAI-1 locus, in sum, explain approximately 5% of the residual variance in multivariable-adjusted PAI-1 levels. For quantitative cardiovascular traits such as circulating biomarkers, defining LD structure in a candidate gene followed by association analyses with both SNPs and haplotypes is an effective approach to localize common susceptibility alleles.

Aged↗

PubMed2025

Discovering diabetes complications-related microRNAs: meta-analyses and pathway modeling approach.

PURPOSE: MicroRNAs(miRNA) play an important role in the pathogenesis of diabetic complications by regulating gene expression. The objective of this paper is to investigate micoRNA expression in diabetic nephropathy (DN), diabetic retinopathy (DR), diabetic neuropathy (DNP), and diabetic cardiopathy (DC). METHODS: We conducted this systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement and retrieved eligible microRNA-related studies of diabetic complications from PubMed, Embase, and Web of science databases. We enriched pathways corresponding to differentially expressed miRNAs using the miRPath tool on the DIANA website, and predicted their target genes with DIANA microT-CDS and TargetScan. RESULTS: Although many of the selected studies were of high scientific quality, the results were heterogeneous. Among the 71 selected articles, 79 miRNAs were differentially expressed in various complications of diabetes, of which miRNA126, miRNA192 and 17 others were reported in at least two or more studies. A total of 156 target genes were predicted and 103 pathways were obtained by KEGG enrichment analysis. CONCLUSION: This comprehensive systematic evaluation provides experimental evidence statistics for miRNAs as circulating biomarkers and highlights promising biomarkers. These results provide preliminary data to further investigate the role of miRNAs in the diagnosis and therapeutic targets of human diabetic complications and support future broader longitudinal studies to better substantiate the role of dysregulated miRNAs as potential biomarkers and therapeutic targets of diabetic complications.

Humans↗

PubMed2005

Conditional risk factors for atherosclerosis.

Although most patients who experience a coronary heart disease (CHD) event have one or more of the conventional risk factors for atherosclerosis, so do many people who have not yet experienced such an event. Therefore, predictive models based on conventional risk factors have a lower than desired accuracy, providing a stimulus to search for new tools to refine CHD risk prediction. In particular, there is intense interest in evaluating circulating biomarkers related to the atherosclerotic process that might add to our ability to better predict CHD risk. One such group of biomarkers was termed conditional risk factors in an American Heart Association/American College of Cardiology statement in 1999. The conditional risk factors include homocysteine, fibrinogen, lipoprotein(a), low-density lipoprotein particle size, and C-reactive protein. This review updates the conditional risk factors. The main focus is on the potential utility of these risk factors, which are currently available to clinicians, in the prediction of CHD risk in asymptomatic persons. The putative mechanisms of risk, available assays, evidence for association with CHD, and the clinical implications thereof are discussed for each of the risk factors.

Arteriosclerosis↗

PubMed1978

Tumor immunology of experimental osteosarcoma.

A spontaneous AP positive C3H murine OS was used to determine the effects of various treatment modalities. AP served as a useful circulating biomarker of the in vivo tumor growth. In animals whose tumor was amputated, the elevation of the marker indicated the presence of pulmonary metastases. It was used to establish the time of recurrence after a partially effective chemotherapy or combination modality. In this model, when the neoplasm was surgically excised at 10 days posttransplantation, 70--80% of the mice showed presence of lung metastases. Specific immunotherapy with irradiated tumor cells did not alter the course of the disease. Passively transferred immune allogeneic cells to tumor bearing mice at an effector to target cell ratio of 1:1 in vivo were ineffective. The murine OS model is extremely useful to plan and institute different combinations of treatment modalities and optimize the conditions for an effective treatment in a relatively short time.

Alkaline Phosphatase↗