Related Biomarkers Research Articles

Update on autoantibodies and related biomarkers in autoimmune inflammatory myopathies.

Purpose of review This manuscript reviews recently published advances in the identification of autoimmune inflammatory myopathies (AIM)-specific and AIM-related autoantibodies considered of value in the workup of patients suspected of having AIM. Newer autoantibodies, developments, and advances in the methodology of testing, the gaps and pitfalls in using these assays as diagnostic biomarkers, and the importance of considering overlap diseases and unique clinical AIM phenotypes are discussed. Recent findings Summary The spectrum of autoantibodies and related biomarkers in AIM continues to expand. Many of these have clear clinical implications in regard to subsets and overlap conditions of AIM, associated malignancy and pathological findings.

Association between air pollution and primary liver cancer in European and east Asian populations: a Mendelian randomization study.

The incidence of primary liver cancer is increasing year by year, with environmental factors playing a non-negligible role. At present, many studies are still disputing whether air pollution is associated with primary liver cancer incidence, and it is difficult to draw causal inferences. Therefore, in this study, we used two-sample Mendelian randomization (MR) to assess the causal relationship between air pollution (including PM2.5, PM2.5-10, PM10, nitrogen dioxide and nitrogen oxides) and primary liver cancer risk and its related biomarkers (Alpha-fetoprotein, Osteopontin, Glypican-3 and Arginase-1). We used large-scale publicly available genome-wide association studies (GWAS) summary data to conduct MR analyses of European and East Asian populations. Inverse variance weighted (IVW) method was used as the main analysis method, and weighted median model, MR-Egger, simple model and weighted model methods were selected for quality control. Heterogeneity was checked by the Cochran's Q test. The MR-Egger regression and the MR-PRESSO global test detect pleiotropy. The sensitivity analysis was performed using the leave-one-out method. Between air pollution and primary liver cancer in either European (PM2.5: p = 0.993; PM2.5-10: p = 0.833; PM10: p = 0.257; nitrogen dioxide: p = 0.215; nitrogen oxides: p = 0.614) or East Asian (PM2.5: p = 0.718; PM2.5-10: p = 0.362; PM10: p = 0.720; nitrogen dioxide: p = 0.101; nitrogen oxides: p = 0.760) populations were found no statistical association. Notably, there was a causal relationship between nitrogen oxides and Arginase-1, a biomarker associated with hepatocellular differentiation, statistically significant associations remained after deletion for single nucleotide polymorphisms (SNPs) associated with alcohol intake frequency, Body mass index (BMI) and cancers (Beta: 4.46; 95%CI: 0.83-8.08; p = 0.015). There was no heterogeneity or pleiotropy in the results. This MR study found no evidence to support a causality between air pollution and primary liver cancer in European and East Asian populations, but nitrogen oxides may affect hepatocellular differentiation.

Decreased 25-Hydroxy Vitamin D Level Is Associated with All-Cause Mortality in Patients with Type 2 Diabetes at High Cardiovascular Risk.

Cardiovascular diseases are among the leading causes of morbidity and mortality, particularly in individuals with type 2 diabetes. There is a need for new biomarkers to improve the prediction of cardiovascular events and overall mortality. We investigated the association of selected atherosclerosis related biomarkers, specifically osteoprotegerin (OPG), 25-hydroxy-vitamin D (25(OH)D), C-reactive protein (CRP), lipopolysaccharide-binding protein (LBP), and asymmetric dimethylarginine (ADMA), with the occurrence of any cardiovascular event or all-cause mortality (primary outcome) during a 5.6-year follow-up of 190 patients with type 2 diabetes. Data were analyzed using logistic regression to adjust for baseline cardiovascular status and cardiovascular risk factors. The primary outcome occurred in 89 participants (46.8%) during the study. When analyzed individually, 25(OH)D, CRP, and LBP significantly predicted the primary outcome in multivariable models. However, in a model that included all biomarkers, only a decreased level of 25(OH)D remained a significant predictor of the primary outcome. Moreover, the level of 25(OH)D significantly predicted all-cause mortality: a reduction of 10 ng/mL was associated with a two-fold increase in all-cause mortality. Our study thus demonstrates that vitamin D deficiency was the strongest factor associated with the primary outcome and all-cause mortality after a 5.6-year follow-up in patients with type 2 diabetes at high cardiovascular risk.

Identification of functional genes regulating gastric cancer progression using integrated bioinformatics analysis.

Gastric cancer (GC) is one of the most common cancers and has a poor prognosis. Treatment of GC has remained unchanged over the past few years. To investigate the potential therapeutic targets and related regulatory biomarkers of GC. We obtained the public GC transcriptome sequencing dataset from the Gene Expression Omnibus database. The datasets contained 348 GC tissues and 141 healthy tissues. In total, 251 differentially expressed genes (DEGs) were identified, including 187 down-regulated genes and 64 up-regulated genes. The DEGs' enriched functions and pathways include Progesterone-mediated oocyte maturation, cell cycle, and oocyte meiosis, Hepatitis B, and the Hippo signaling pathway. Survival analysis showed that BUB1, MAD2L1, CCNA2, CCNB1, and BIRC5 may be associated with regulation of the cell cycle phase mitotic spindle checkpoint pathway. We selected 26 regulated genes with the aid of the protein-protein interaction network analyzed by Molecular Complex Detection. We focused on three critical genes, which were highly expressed in GC, but negatively related to patient survival. Furthermore, we found that knockdown of BIRC5, TRIP13 or UBE2C significantly inhibited cell proliferation and induced cell apoptosis. In addition, knockdown of BIRC5, TRIP13 or UBE2C increased cellular sensitivity to cisplatin. Our study identified significantly upregulated genes in GC with a poor prognosis using integrated bioinformatics methods.

Pyroptosis -related potential diagnostic biomarkers in steroid-induced osteonecrosis of the femoral head

PurposeSteroid-induced necrosis of the femoral head (SONFH) is a refractory orthopedic hip disease occurring in young and middle-aged people, with glucocorticoids being the most common cause. Previous experimental studies have shown that cell pyroptosis may be involved in the pathological process of SONFH, but its pathogenesis in SONFH is still unclear. This study aims to screen and validate potential pyroptosis-related genes in SONFH diagnosis by bioinformatics analysis to further elucidate the mechanism of pyroptosis in SONFH.MethodsThere were 33 pyroptosis-related genes obtained from the prior reviews. The mRNA expression was downloaded from GSE123568 dataset in the Gene Expression Omnibus (GEO) database, including 10 non-SONFH (following steroid administration) samples and 30 SONFH samples. The pyroptosis-related differentially expressed genes involved in SONFH were identified with “affy” and “limma” R package by intersecting the GSE123568 dataset with pyroptosis genes. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the pyroptosis-related differentially expressed genes involved in SONFH were conducted by “clusterProfiler” R package and visualized by “GOplot” R package. Then, the correlations between the expression levels of the pyroptosis-related differentially expressed genes involved in SONFH were confirmed with “corrplot” R package. Moreover, the protein–protein interaction (PPI) network was analysed by using GeneMANIA database. Next, The ROC curve of pyroptosis-related differentially expressed genes were analyzed by “pROC” R package.ResultsA total of 10 pyroptosis-related differentially expressed genes were identified between the peripheral blood samples of SONFH patients and non-SONFH patients based on the defined criteria, including 20 upregulated genes and 10 downregulated genes. The GO and KEGG pathway enrichment analyses revealed that these 10 pyroptosis-related differentially expressed genes involved in SONFH were particularly enriched in cysteine-type endopeptidase activity involved in apoptotic process, positive regulation of interleukin-1 beta secretion and NOD-like receptor signaling pathway. Correlation analysis revealed significant correlations among the 10 differentially expressed pyroptosis-related genes involved in SONFH. The PPI results demonstrated that the 10 pyroptosis-related differentially expressed genes interacted with each other. Compared to non-SONFH samples, these pyroptosis-related differentially expressed genes had good predictive diagnostic efficacy (AUC = 1.000, CI = 1.000–1.000) in the SONFH samples, and NLRP1 had the highest diagnostic value (AUC: 0.953) in the SONFH samples.ConclusionsThere were 10 potential pyroptosis-related differentially expressed genes involved in SONFH were identified via bioinformatics analysis, which might serve as potential diagnostic biomarkers because they regulated pyroptosis. These results expand the understanding of SONFH associated with pyroptosis and provide new insights to further explore the mechanism of action and diagnosis of pyroptosis associated in SONFH.

Associations of Alzheimer's-related plasma biomarkers with cognitive decline in Parkinson's disease.

Parkinson's disease (PD) is associated with cognitive decline through multiple mechanisms, including Alzheimer's disease (AD) pathology and cortical Lewy body involvement. However, its underlying mechanisms remain unclear. Recently, AD-related plasma biomarkers have emerged as potential tools for predicting abnormal pathological protein accumulation. We aimed to investigate the association between AD-related plasma biomarkers and cognitive decline in PD patients. Plasma biomarkers were measured in 70 PD patients (49 with nondemented Parkinson's disease (PDND) and 21 with Parkinson's disease dementia (PDD)) and 38 healthy controls (HCs) using a single-molecule array. The study evaluated (1) the correlation between plasma biomarkers and clinical parameters, (2) receiver operating characteristic curves and areas under the curve to evaluate the discrimination capacity of plasma biomarkers among groups, and (3) a generalized linear model to analyze associations with Addenbrooke's Cognitive Examination-Revised and Montreal Cognitive Assessment-Japanese version scores. Plasma glial fibrillary acidic protein significantly correlated with cognitive function tests, including all subdomains, with a notable increase in the PDD group compared with the HC and PDND groups, while plasma neurofilament light chain captured both cognitive decline and disease severity in the PDND and PDD groups. Plasma beta-amyloid 42/40 and pholphorylated-tau181 indicated AD pathology in the PDD group, but plasma beta-amyloid 42/40 was increased in the PDND group compared with HCs and decreased in the PDD group compared with the PDND group. AD-related plasma biomarkers may predict cognitive decline in PD and uncover underlying mechanisms suggesting astrocytic pathologies related to cognitive decline in PD.

SOD mineralized zeolitic imidazole framework-8 for the treatment of chemotherapy-related acute kidney injury

Acute kidney injury (AKI), a prevalent and fatal adverse event, seriously affects cancer patients undergoing chemotherapy. The most important pathological mechanism of AKI is oxidative stress from reactive oxygen species (ROS). Currently, ROS scavenging is a promising strategy to manage the risk of chemotherapy-induced AKI. Herein, we successfully synthesized SOD@ZIF-8 nanoparticles by biomimetic mineralization, which were taken up by cells and could improve cell viability by limiting oxidative stress damage, as found in in vitro studies. Moreover, SOD@ZIF-8 nanoparticles exhibit broad-spectrum antioxidant properties in addition to significant renal accumulation in AKI mice, preventing clinically related cisplatin-induced AKI in murine models. AKI alleviation in the model was validated by measuring blood serum, staining kidney tissue, and related biomarkers. SOD@ZIF-8 nanoparticle therapeutic efficiency exceeds NAC, a small molecular antioxidant functioning through free radical scavenging. The results suggest SOD@ZIF-8 nanoparticles as a potential therapeutic option for AKI and other ROS-related disorders.

Conservation strip-till modifies rhizosphere ammonia-oxidizing archaea and bacteria, increases nitrate accumulation and promotes maize growth at grain filling stage

Strip-till (ST) is a conservation tillage wherein the “inter-row” is not tilled and remains covered with protective residues, while the “row zone” is strip tilled. In comparison to conventional ridge tillage (CT), maize yield under ST is maintained due to its growth recovery at grain filling stage (GFS), though its growth lag at early growth stage in cold regions. To explore microbial mechanisms underlying the growth recovery, compared with CT, we investigated relationships among rhizosphere ammonia-oxidizing archaea and bacteria (AOA and AOB), rhizosphere soil characteristics, and maize growth under ST through a two-year field experiment in a Mollisol of Northeast China. Compared with CT, ST led to rhizosphere NO3--N accumulation at 0–5 cm location, which positively correlated with maize N accumulation and growth at GFS. ST significantly affected rhizosphere AOA and AOB communities at 0–5 and 20–30 cm locations, and decreased AOA abundance, norank_p_Thaumarchaeota relative abundance and bio-markers, but increased AOB abundance, richness, Nitrosospira relative abundance and bio-markers at 0–5 cm location. ST obviously increased the number of OTU hubs belonging to AOB Nitrosospira in networks and their complexity at 0–5 cm location. AOB community play a more important function role than AOA at 0–5 cm location. Rhizosphere NO3--N accumulation, maize N accumulation and growth recovery were closely related with AOB (especially Nitrosospira), but not AOA. It is concluded that, in contrast to CT, ST mainly stimulate rhizosphere AOB activity at 0–5 cm location (especially Nitrosospira) during grain filling stage, which contributes to more rhizosphere NO3--N accumulation and maize N absorption and faster growth. Our findings provide a theoretical basis for efficient crop-soil management to increase maize productivity under conservation tillage system.

Mixtures of urinary concentrations of phenols and phthalate biomarkers in relation to the ovarian reserve among women attending a fertility clinic

Although prior studies have found associations of the ovarian reserve with urinary concentrations of some individual phenols and phthalate metabolites, little is known about the potential associations of these chemicals as a mixture with the ovarian reserve. We investigated whether mixtures of four urinary phenols (bisphenol A, butylparaben, methylparaben, propylparaben) and eight metabolites of five phthalate diesters including di(2-ethylhexyl) phthalate were associated with markers of the ovarian reserve among 271 women attending a fertility center who enrolled in the Environment and Reproductive Health study (2004–2017). The analysis was restricted to one outcome per study participant using the earliest outcome after the last exposure assessment. Ovarian reserve markers included lower antral follicle count (AFC) defined as AFC < 7, circulating serum levels of day 3 follicle stimulating hormone (FSH) assessed by immunoassays, and diminished ovarian reserve (DOR) defined as either AFC < 7, FSH > 10 UI/L or primary infertility diagnosis of DOR. We applied Bayesian Kernel Machine Regression (BKMR) and quantile g-computation to estimate the joint associations and assess the interactions between chemical exposure biomarkers on the markers of the ovarian reserve while adjusting for confounders. Among all 271 women, 738 urine samples were collected. In quantile g-computation models, a quartile increase in the exposure biomarkers mixture was not significantly associated with lower AFC (OR = 1.10, 95 % CI = 0.52, 2.30), day 3 FSH levels (Beta = 0.30, 95 % CI = −0.32, 0.93) or DOR (OR = 1.02, 95 % CI = 0.52, 2.05). Similarly, BKMR did not show any evidence of associations between the mixture and any of the studied outcomes, or interactions between chemicals. Despite the lack of associations, these results need to be explored among women in other study cohorts.

ERS Mediated by GRP-78/PERK/CHOP Signaling Is Involved in Fluoride-Induced Ameloblast Apoptosis.

Fluoride can be widely ingested from the environment, and its excessive intake could result in adverse effects. Dental fluorosis is an early sign of fluoride toxicity which can cause esthetic and functional problems. Though apoptosis in ameloblasts is one of the potential mechanisms, the specific signal cascade is in-conclusive. High-throughput sequencing and molecular biological techniques were used in this study to explore the underlying pathogenesis of dental fluorosis, for its prevention and treatment. A fluorosis cell model was established. Viability and apoptosis rate of mouse ameloblast-derived cell line (LS8 cells) was measured using cell counting kit-8 (CCK-8) assay and flow cytometry analysis. Cells were harvested with or without 2-mM sodium fluoride (NaF) stimulation for high-throughput sequencing. Based on the sequencing data, subcellular structures, endoplasmic reticulum stress (ERS), and apoptosis related biomarkers were verified using transmission electron microscopy, quantitative real-time polymerase chain reaction, and Western blotting techniques. Expression of ERS markers, apoptosis related proteins, and enamel formation enzymes were detected using Western blotting after addition of 4-phenylbutyrate (4-PBA). NaF-inhibited LS8 cells displayed time- and dose- dependent viability. Additionally, apoptosis and morphological changes were observed. RNA-sequencing data showed that protein processing in endoplasmic reticulum was obviously affected. ERS and apoptosis were induced by excessive NaF. Downregulation of kallikrein-related peptidase 4 (KLK4) was also observed. Inhibition of ERS by 4-PBA rescued the apoptotic and functional protein changes in cells. Excessive fluoride induces apoptosis by activating ERS, which is mediated by GRP-78/PERK/CHOP signaling. Key proteinase is present in maturation-stage enamel; KLK4 was also affected by fluoride, but rescued by 4-PBA. This study presents a possibility for therapeutic strategies for dental fluorosis, while further exploration is required.

Cellular antioxidant activity measurement: An alternative to chemical antioxidant methods?

AbstractOxidative stress occurs when the production of reactive oxygen species (ROS) overpasses their degradation and buffering by endogenous antioxidants and those derived from the diet (exogenous antioxidants). In food science and nutrition, assessing antioxidant activity relies on chemical reactions—chemical test‐tube assays—and human and murine cell lines. Usually, an ROS inductor, such as hydrogen peroxide (H2O2) or peroxyl radicals (ROO•), is used to induce oxidation. Some biomarkers related to endogenous protection (i.e., catalase, superoxide dismutase, and glutathione reductase), oxidation‐end products (i.e., malondialdehyde), and intracellular ROS generation can be quantitatively determined. Herein, some insights into using human cell lines and related biomarkers are described, and the downsides of using chemical antioxidant assays are explained. In conclusion, research on antioxidants should be based on using relevant human cell cultures. In contrast, chemical antioxidant assays should be limited to an initial screening as their physiological importance is negligible.

Sodium Selenite Modulates Global Activation of Proinflammatory M1-like Macrophages, Necroinflammation and M1-like/M2-like Dichotomy at the Onset of Human Type 1 Diabetes.

The study aims to show that sodium selenite (Ss) would have an immunomodulatory effect on the functional activity of proinflammatory macrophages (Mφs) during their extended extracellular activation at the onset of human type 1 diabetes (T1D). Exacerbated activation of proinflammatory "M1" macrophages (Mφs) can promote chronic local pancreatic islet inflammation and T1D development. We investigated the ex vivo effects of Ss on the immune modulation of global/extended activation of human proinflammatory M1-like Mφs. Experiments were carried out on primary monocytes-derived Mφs (MDMs). The levels of IL-1β, TNF-α, H2O2 and intracellular free calcium ions (ifCa2+), and the ratios of IL-1β-to-IL-10 and TNF-α-to-IL-10 were markedly increased in T1D Mφs than in healthy control Mφs. Conversely, both IL-10 production and arginase 1 (ARG1) activity were downregulated in T1D Mφs. Additionally, Ss treatment induced a marked downregulation of respiratory burst, ifCa2+ levels, M1-like Mφ-associated inducible nitric oxide (NO) synthase (iNOS) activity, cell necrosis and related necroinflammation biomarkers, including IL-1β and TNF-α, CD14 expression, and the ratios of iNOS-to-ARG1, IL-1β-to-IL-10, and TNF-α-to-IL-10. Moreover, Ss upregulated anti-inflammatory "M2-like" Mφ activity as demonstrated by ARG1 activity and IL-10 production, as well as phagocytosis capacity. Ss exerts a potent immunomodulatory role on functional activities of human proinflammatory T1D M1-like Mφs subjected to extended activation, as well as on the M1-like/M2-like dichotomy. Additionally, the current study provides a novel therapeutic approach using Ss to promote the anti-inflammatory function of Mφs at the onset of T1D.

HS-SPME-GC-MS Untargeted Analysis of Normal Rat Organs Ex Vivo: Differential VOC Discrimination and Fingerprint VOC Identification.

The investigation of volatile organic compounds (VOCs) in human metabolites has been a topic of interest as it holds the potential for the development of non-invasive technologies to screen for organ lesions in vivo. However, it remains unclear whether VOCs differ among healthy organs. Consequently, a study was conducted to analyze VOCs in ex vivo organ tissues obtained from 16 Wistar rats, comprising 12 different organs. The VOCs released from each organ tissue were detected by the headspace-solid phase microextraction-gas chromatography-mass spectrometry technique. In the untargeted analysis of 147 chromatographic peaks, the differential volatiles of rat organs were explored based on the Mann-Whitney U test and fold change (FC > 2.0) compared with other organs. It was found that there were differential VOCs in seven organs. A discussion on the possible metabolic pathways and related biomarkers of organ differential VOCs was conducted. Based on the orthogonal partial least squares discriminant analysis and receiver operating characteristic curve, we found that differential VOCs in the liver, cecum, spleen, and kidney can be used as the unique identification of the corresponding organ. In this study, differential VOCs of organs in rats were systematically reported for the first time. Profiles of VOCs produced by healthy organs can serve as a reference or baseline that may indicate the presence of disease or abnormalities in the organ's function. Differential VOCs can be used as the fingerprint of organs, and future integration with metabolic research may contribute to the development of healthcare.

To Assess the Role of Immune Infiltrating Immune Cells of Patients With Chronic Heart Failure With Atrial Fibrillation and Nursing Care in These Patients.

This research aimed to assess the role of immune infiltrating immune cells of patients with chronic heart failure with atrial fibrillation and nursing care inthesepatients. For this aim, 400 patients from 22 centres across our nations were recruited in the index cohort based on worsening signs/symptoms and poor management of HF. The validation cohort consisted of patients who had previously participated in the index cohort. The primary goal was to reduce all-cause mortality as well as unscheduled hospitalisations due to heart failure. Hospitalizations for heart failure (HF), total mortality, and death attributable to cardiovascular disease were secondary objectives. Results showed that interleukin-6 (IL-6) levels in patients ranged from 3.1 to 11.21 pg/mL on average, with 228 patients (or 57% of the total) having IL-6 levels that were higher than the 95th percentile of normal values (> 4.45 pg/mL). The average age of the group was 69.85±9.68 years, and there were 295 males in the group (73.75 percent). 17 Patients who had higher levels of IL-6 tended to be older, more frequently suffered from heart failure with preserved ejection fraction (HFpEF), and more frequently suffered from anaemia, diabetes, and atrial fibrillation. Patients who had higher levels of IL-6 also had a greater likelihood of suffering from these conditions. Patients who had higher levels of IL-6 also had a shorter distance travelled during the 6MWT and had a lower chance of completing the test. Both test completion [OR (95% CI) per doubling of IL-6: 0.81 (0.71 - 0.91), P< 0.001] and total distance covered [B (95% CI) per doubling of IL-6: 28.11 (32.58 to-21.98), P< 0.001] were negatively associated with increasing levels of IL-6, Patients who had high levels of IL-6 had higher median hepcidin levels than patients who had low levels of IL-6. This was discovered by comparing the two groups' hepcidin levels. There was a correlation between increased levels of IL-6 and increased levels of NT-proBNP and CRP, as well as a reduction in eGFR. In conclusion, independent predictors of IL-6 were younger age, high-flow partial ejection fraction (HFpEF), atrial fibrillation (AF), iron insufficiency, and higher levels of NT-proBNP, PCT, hepcidin, and TNF-/IL-1 related biomarkers. Last but not least, IL-6 levels in the plasma were able to predict death and/or hospitalisation due to HF on their own, although they did not contribute to differentiation in prior models.

Molecular mechanisms contributing to the development of beef sensory texture and flavour traits and related biomarkers: Insights from early post-mortem muscle using label-free proteomics

Beef sensory quality comprises a suite of traits, each of which manifests its ultimate phenotype through interaction of muscle physiology with environment, both in vivo and post-mortem. Understanding variability in meat quality remains a persistent challenge, but omics studies to uncover biological connections between natural variability in proteome and phenotype could provide validation for exploratory studies and offer new insights. Multivariate analysis of proteome and meat quality data from Longissimus thoracis et lumborum muscle samples taken early post-mortem from 34 Limousin-sired bulls was conducted. Using for the first-time label-free shotgun proteomics combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS), 85 proteins were found to be related with tenderness, chewiness, stringiness and flavour sensory traits. The putative biomarkers were classified in five interconnected biological pathways; i) muscle contraction, ii) energy metabolism, iii) heat shock proteins, iv) oxidative stress, v) regulation of cellular processes and binding. Among the proteins, PHKA1 and STBD1 correlated with all four traits, as did the GO biological process ‘generation of precursor metabolites and energy’. Optimal regression models explained a high level (58–71%) of phenotypic variability with proteomic data for each quality trait. The results of this study propose several regression equations and biomarkers to explain the variability of multiple beef eating quality traits. Thanks to annotation and network analyses, they further suggest protein interactions and mechanisms underpinning the physiological processes regulating these key quality traits. SignificanceThe proteomic profiles of animals with divergent quality profiles have been compared in numerous studies; however, a wide range of phenotypic variation is required to better understand the mechanisms underpinning the complex biological pathways correlated with beef quality and protein interactions. We used multivariate regression analyses and bioinformatics to analyse shotgun proteomics data to decipher the molecular signatures involved in beef texture and flavour variations with a focus on multiple quality traits. We developed multiple regression equations to explain beef texture and flavour. Additionally, potential candidate biomarkers correlated with multiple beef quality traits are suggested, which could have utility as indicators of beef overall sensory quality. This study explained the biological process responsible for determining key quality traits such as tenderness, chewiness, stringiness, and flavour in beef, which will provide support for future beef proteomics studies.

Weighing poor immunometabolic health in relatives for severity of affective symptoms: A study of patients with depressive and anxiety disorders and their siblings

BackgroundAffective (i.e. depressive and anxiety) disorders often co-occur with immunometabolic diseases and related biological pathways. Although many large population-based and meta-analytic studies have confirmed this link in community and clinical samples, studies in at-risk samples of siblings of persons with affective disorders are lacking. Furthermore, this somatic-mental co-occurrence may be partially explained by familial clustering of the conditions. First, we examined whether the association between a wide range of immunometabolic diseases and related biomarker based risk-profiles with psychological symptoms replicates in at-risk siblings of probands with affective disorders. Second, leveraging on a sibling-pair design, we disentangled and quantified the effect of probands’ immunometabolic health on siblings’ psychological symptoms and on the association between immunometabolic health and these symptoms in siblings. MethodsThe sample included 636 participants (Mage = 49.7; 62.4% female) from 256 families, each including a proband with lifetime depressive and/or anxiety disorders and at least one of their sibling(s) (N = 380 proband-sibling pairs). Immunometabolic health included cardiometabolic and inflammatory diseases, body mass index (BMI), and composite metabolic (based on the five metabolic syndrome components) and inflammatory (based on interleukin-6 and C-reactive protein) biomarker indices. Overall affective symptoms and specific atypical, energy-related depressive symptoms were derived from self-report questionnaires. Mixed-effects analyses were used to model familial clustering. ResultsIn siblings, inflammatory disease (γ = 0.25, p = 0.013), higher BMI (γ = 0.10, p = 0.033) and metabolic index (γ = 0.28, p < 0.001) were associated with higher affective symptoms, with stronger associations for atypical, energy-related depressive symptoms (additionally associated with cardiometabolic disease; γ = 0.56, p = 0.048). Immunometabolic health in probands was not independently associated with psychological symptoms in siblings nor did it moderate the association between immunometabolic health and psychological symptoms estimated in siblings. ConclusionsOur findings demonstrate that the link between later life immunometabolic health and psychological symptoms is consistently present also in adult siblings at high risk for affective disorders. Familial clustering did not appear to have a substantial impact on this association. Instead, individual lifestyle, rather than familial factors, may have a relatively higher impact in the clustering of later life immunometabolic conditions with psychological symptoms in at-risk adult individuals. Furthermore, results highlighted the importance of focusing on specific depression profiles when investigating the overlap with immunometabolic health.

Platelets-related signature based diagnostic model in rheumatoid arthritis using WGCNA and machine learning.

Rheumatoid arthritis (RA) is an autoinflammatory disease that may lead to severe disability. The diagnosis of RA is limited due to the need for biomarkers with both reliability and efficiency. Platelets are deeply involved in the pathogenesis of RA. Our study aims to identify the underlying mechanism and screening for related biomarkers. We obtained two microarray datasets (GSE93272 and GSE17755) from the GEO database. We performed Weighted correlation network analysis (WGCNA) to analyze the expression modules in differentially expressed genes identified from GSE93272. We used KEGG, GO and GSEA enrichment analysis to elucidate the platelets-relating signatures (PRS). We then used the LASSO algorithm to develop a diagnostic model. We then used GSE17755 as a validation cohort to assess the diagnostic performance by operating Receiver Operating Curve (ROC). The application of WGCNA resulted in the identification of 11 distinct co-expression modules. Notably, Module 2 exhibited a prominent association with platelets among the differentially expressed genes (DEGs) analyzed. Furthermore, a predictive model consisting of six genes (MAPK3, ACTB, ACTG1, VAV2, PTPN6, and ACTN1) was constructed using LASSO coefficients. The resultant PRS model demonstrated excellent diagnostic accuracy in both cohorts, as evidenced by area under the curve (AUC) values of 0.801 and 0.979. We elucidated the PRSs occurred in the pathogenesis of RA and developed a diagnostic model with excellent diagnostic potential.

CEBP-β and PLK1 as Potential Mediators of the Breast Cancer/Obesity Crosstalk: In Vitro and In Silico Analyses.

Over the last two decades, obesity has reached pandemic proportions in several countries, and expanding evidence is showing its contribution to several types of malignancies, including breast cancer (BC). The conditioned medium (CM) from mature adipocytes contains a complex of secretes that may mimic the obesity condition in studies on BC cell lines conducted in vitro. Here, we report a transcriptomic analysis on MCF-7 BC cells exposed to adipocyte-derived CM and focus on the predictive functional relevance that CM-affected pathways/processes and related biomarkers (BMs) may have in BC response to obesity. CM was demonstrated to increase cell proliferation, motility and invasion as well as broadly alter the transcript profiles of MCF-7 cells by significantly modulating 364 genes. Bioinformatic functional analyses unraveled the presence of five highly relevant central hubs in the direct interaction networks (DIN), and Kaplan-Meier analysis sorted the CCAAT/enhancer binding protein beta (CEBP-β) and serine/threonine-protein kinase PLK1 (PLK1) as clinically significant biomarkers in BC. Indeed, CEBP-β and PLK1 negatively correlated with BC overall survival and were up-regulated by adipocyte-derived CM. In addition to their known involvement in cell proliferation and tumor progression, our work suggests them as a possible "deus ex machina" in BC response to fat tissue humoral products in obese women.

1542-P: Commercially Available Aspartame-Based Sweetener Damages Morphology of Major Organs Both in Normal and Type 2 Diabetic Rats

Non-nutritive sweeteners (NNS) such as aspartame have become highly popular as sugar substitutes for diabetics. Majority of studies have reported controversial results and used aspartame in its pure form, which is not consumed by people practically. Hence, the present study was aimed at investigating the effects of commercially available aspartame-based sweetener on diabetes related parameters and its associated complications in both normal and type 2 diabetic rats. Seven-week-old male Sprague-Dawley rats were randomly divided into four groups, namely: Normal Control (NC), Toxicological Aspartame (TASP), Diabetic Control (DBC) and Diabetic Aspartame (DASP). Type 2 diabetes was induced experimentally in the DBC and DASP groups only and animals with non-fasting blood glucose levels &amp;gt;300 mg/dL were considered as diabetic. During 13 weeks experimental period, the control groups received normal drinking water, whilst TASP and DASP groups were given aspartame-containing NNS solutions, ad libitum, at concentrations equivalent to the sweetness of 20% and 10% sucrose solution, respectively. Treatment with toxicological aspartame resulted in significantly reduced serum fructosamine and creatinine levels in normal rats, when brain, heart, liver, kidney and pancreatic tissue morphologies were significantly damaged in both normal and diabetic rats. The data of this study suggest that although aspartame-based NNS may not have higher degree of detrimental effects on diabetes associated parameters, the significantly damaged morphology of the major organ tissues as well as deterioration of related serum biomarkers both in normal and diabetic conditions raises a concern of its use as a NNS in various food and food products. Disclosure S.N.Dlamini: None. S.Islam: None. Funding South African Sugar Association (Project 233)

#3915 RELATIONSHIP BETWEEN URINARY DCR2/CR LEVEL AND POOR PROGNOSIS OF DIABETIC NEPHROPATHY

Abstract Background and Aims Diabetic kidney disease(DKD) has a high prevalence rate and many complications, and it has become the main reason for the progression of chronic kidney disease to end-stage renal disease (ESRD). At present, some clinical biomarkers, such as urinary albumin / creatinine ratio (ACR), serum creatinine and cystatin C, are of positive significance in evaluating the course of DKD, but these indicators are greatly affected by the state of the body itself, which can no longer meet the clinical needs. Decoy receptor 2 (DcR2) is the transmembrane receptor of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and is a biomarker of cell senescence and apoptosis resistance. Our previous study found that the level of urinary DcR2/Cr is closely related to renal function damage and renal interstitial injury. Considering that there is still a lack of research on predicting the poor prognosis of DKD with related biomarkers, this study detected the level of DcR2/Cr in the urine of patients with DKD for the first time to analyze the relationship between the poor prognosis of DKD and to determine whether urinary DcR2/Cr can be used as an index to predict the poor prognosis of DKD. Method A total of 181 inpatients with DKD were collected from the Department of Nephrology of Daping Hospital from 2018 to 2022, of which 121 urine samples were collected. The clinical data of the patients were collected and divided into three quantiles according to the level of urinary DcR2/Cr. Group 1: DcR2/Cr &amp;lt; 321ng / mmol. group 2: 321 ≤ DcR2/Cr ≤ 505ng / mmol. group 3: DcR2/Cr &amp;gt; 505ng / mmol. The adverse prognosis was based on the occurrence of end point events. Multivariate Cox regression analysis was used to evaluate the relationship between urinary DcR2/Cr level and poor prognosis of DKD. ROC curve was used to analyze the value of biomarkers in predicting the poor prognosis of DKD. Results With the increase of urinary DcR2/Cr level, the levels of urinary Microalbumin, ACR, NAG, CYC and serum creatinine increased, while urinary creatinine and eGFR decreased gradually. Correlation analysis showed that the level of DcR2/Cr was positively correlated with ACR, cystatin C and NAG, and negatively correlated with eGFR, while DcR2/Cr was positively correlated with IFTA score, renal artery hyaline change score and renal arteriosclerosis score. Cox regression analysis showed that there was a significant correlation between the level of DcR2/Cr and the occurrence of poor prognosis (corrected by the model), and the risk of poor prognosis in the DcR2/Cr3 group was 9.903 times higher than that in the DcR2/Cr1 group. Kaplan-Meier survival curve showed that the higher the level of DcR2/Cr, the worse the prognosis. ROC curve analysis showed that the area under urinary DcR2 curve was the largest (AUC = 0.811), which was higher than ACR, CYC and SCr, and the best intercept value was 389.0ng/mmol. Conclusion Urinary DcR2/Cr is superior to ACr, Scr, Cyc and other clinical indexes in predicting the poor prognosis of DKD. It is an effective biomarker for predicting poor prognosis of DKD.