Individual Serum Research Articles

CORRELATION BETWEEN MAGNESIUM AND CALCIUM LEVELS ON HEALTH IN THE ELDERLY WITH DEGENERATIVE TYPE 2 DIABETES MELLITUS

Diabetes Mellitus (DM) is a metabolic disorder characterized by elevated blood glucose levels due to decreased insulin secretion from pancreatic beta cells or insulin resistance. Magnesium and calcium are essential minerals that play crucial roles in various enzymatic activities, significantly influencing important biological functions, particularly in relation to metabolic syndrome. The purpose of the research is to investigate the correlation between magnesium and calcium levels in the serum of elderly individuals with type 2 diabetes mellitus. The study method is descriptive observation with cross-sectional studies. The examination sample used 25 serum samples of people with diabetes with age inclusion criteria over 50 years old without any other degenerative diseases. The analysis of the data from the results of the study was then carried out by the SpSS test of the relationship between magnesium levels and the condition of type 2 DM, especially in the context of aging and its impact on metabolic health. Based on the examination of magnesium levels using the xylidil blue method, 23 patients (92%) showed normal results, while 2 patients (8%) showed numbers above normal on average. There was no significant relationship between blood sugar and magnesium levels, blood sugar with calcium levels, and between magnesium with calcium with a significance of p 0.058, p 0.179, and p 0,114, respectively. The findings of this study could enhance the understanding of the complex interactions between these essential minerals and their potential roles in managing metabolic syndrome, ultimately contributing to better health outcomes for older adults with DM.

MSC-sEVs exacerbate senescence by transferring bisecting GlcNAcylated GPNMB

BackgroundThe senescence of bone marrow mesenchymal stem cells (BMMSCs) is increasingly recognized as a critical factor contributing to the pathophysiology of age-related diseases. Recent studies suggest that small extracellular vesicles (sEVs) derived from the serum of elderly individuals may play a pivotal role in promoting BMMSC senescence. Glycoprotein non-metastatic melanoma protein B (GPNMB), a type I transmembrane glycoprotein, is upregulated during cellular senescence and can regulate stem cell ageing. However, the precise mechanisms by which GPNMB influences BMMSCs senescence remain poorly understood. Understanding this relationship could provide valuable insights into therapeutic strategies for enhancing BMMSCs function and mitigating age-related degeneration.MethodsIn this study, we conducted comprehensive in vitro experiments to elucidate the effects of sEVs isolated from the serum of elderly donors on the senescence of BMMSCs. We employed advanced proteomic analysis to quantify the expression levels of GPNMB in both BMMSCs and sEVs. Statistical methods were utilized to investigate the correlations between GPNMB expression, glycosylation modifications, and established senescence markers.ResultsOur findings demonstrate a robust positive correlation between the expression of GPNMB in BMMSCs and sEVs and the induction of cellular senescence. Notably, we observed that elevated levels of GPNMB, particularly those bearing bisecting N-acetylglucosamine (GlcNAc) modifications, significantly enhance the senescent phenotype of BMMSCs. Furthermore, we identified the bisecting GlcNAc modification at the Asn 249 residue of GPNMB as a critical determinant for its senescence-promoting function.ConclusionsThis study elucidates the substantial role of sEVs derived from mesenchymal stem cells in exacerbating BMMSC senescence through mechanisms that are critically dependent on the presence of bisecting GlcNAcylated GPNMB. These insights emphasize the necessity of targeting glycosylation modifications of GPNMB in the design of novel senolytic therapies aimed at mitigating cellular ageing and its associated pathologies.

Elevated Serum Cytokines as Biomarkers for Type 1 Diabetes Mellitus in Diyala Province

The study aims to examine the levels of cytokines in the serum of individuals with type 1 diabetes mellitus and compare these levels to those of healthy controls. This research aimed to assess the levels of some cytokines that includes IL-4, IL-9, IL-13, IL-35, IL-12, IL-17, IL-21 and IL-33 in Type I diabetes mellitus. In this study, 60 samples were collected from patients and 30 samples from healthy individuals, collected during the period from the of July 2023 to the March 2024.Results of this study showed a significant increase in the concentration of IL-4, IL-9, IL-13, IL-35, IL-12, IL-17, IL-21 and IL-33 in the serum of type 1 diabetes mellitus with the control group there were [10.22±2.065, 73.983±5.117, 35.90±3.343, 3.10±1.612, 19.80±3.433, 20.86±4.010,70.75±8.57, and 398.71±47.157, respectively] than in healthy groups [6.793±0.924, 47.00±5.535, 20.72±2.534, 1.01±10.597, 10.34±2.036, 10.79±1.818, 44.83±7.201 and 277.59±39.451, respectively. The results of the current study showed an imbalance in cytokines production that includes IL 4, IL 9, IL 13, IL 35, IL 12, IL 17, IL 21 and IL 33 in type 1 diabetes mellitus [T1DM] patients. The imbalance between pro- and anti-inflammatory cytokines could contribute to pancreatic β-cell destruction, offering insights for potential biomarkers and future therapies.

Skin-Interfaced Wearable Sensor for Long-Term Reliable Monitoring of Uric Acid and pH in Sweat.

Wearable sweat sensors offering real-time monitoring of biomarker levels suffer from stability and accuracy issues, primarily due to low biomarker concentrations, fluctuating sweat pH, and material detachment from sensor deformation. Here, we developed a wearable sensing system integrated with two advanced electrodes and a flexible microchannel for long-term reliable monitoring of sweat pH and uric acid (UA). By printing the ink doped with nanomaterials (Co3O4@CuCo2O4 and polyaniline), we achieved highly stable electrodes for the direct analysis of perspiration, without additional surface modification. Additionally, real-time pH analysis provided a means for sensitivity calibration, reducing the effect of individual metabolism and exercise intensity. As a result, the wearable sensing system for effective gout management was validated by accurately tracking the UA fluctuations in serum and sweat of hyperuricemia patients and healthy individuals. These findings offer a reliable method for tracking biomarkers to assess personal health.

Long-term increase in soluble interleukin-6 receptor levels in convalescents after mild COVID-19 infection.

Serum levels of interleukin-6 (IL-6) are increased in COVID-19 patients. IL-6 is an effective therapeutic target in inflammatory diseases and tocilizumab, a monoclonal antibody that blocks signaling via the IL-6 receptor (IL-6R), is used to treat patients with severe COVID-19. However, the IL-6R exists in membrane-bound and soluble forms (sIL-6R), and the sIL-6R in combination with soluble glycoprotein 130 (sgp130) forms an IL-6-neutralizing buffer system capable of neutralizing small amounts of IL-6. In this study, we analyzed serum levels of IL-6, sIL-6R and sgp130 in the serum of COVID-19 convalescent individuals with a history of mild COVID-19 disease and in acute severely ill COVID-19 patients compared to uninfected control subjects. Furthermore, we used single cell RNA sequencing data in order to determine which immune cell types are sources and targets of the individual cytokines and whether their expression is altered in severe COVID-19 patients. We find that sIL-6R levels are not only increased in acute severely ill patients, but also in convalescents after a mild COVID-19 infection. We show that this increase in sIL-6R results in an enhanced capacity of the sIL-6R/sgp130 buffer system, but that significantly enhanced free IL-6 is still present due to an overload of the buffer. Further, we identify IL-6 serum levels, age and the number of known pre-existing medical conditions as crucial determinants of disease outcome for the patients. We also show that IL-11 has no major systemic role in COVID-19 patients and that sCD25 is only increased in acute severely ill COVID-19 patients, but not in mild convalescent individuals. In conclusion, our study shows long-lasting alterations of the IL-6 system after COVID-19 disease, which might be relevant when applying anti-IL-6 or anti-IL-6R therapy.

Oral supplementation with propionate is reflected in the serum of healthy individuals.

Short-chain fatty acids (SCFAs), including propionic acid (PA), are key in immunological research. Supplementing PA has shown benefits for autoimmune diseases. A comprehensive understanding of the PA pharmacokinetics is essential for the optimal design and execution of studies utilizing orally administered PA. We propose two methods of measuring PA in serum, carried out by different laboratories. Blood samples from 20 volunteers were collected hourly following PA supplementation. Serum propionate quantification was performed with two independent mass spectrometry-based (MS) analyses, including liquid-chromatography (LC)-MS and direct-infusion (DI)-MS. PA levels increased within 1 h of ingestion of 500 mg PA. Serum concentrations ranged from 1.3 to 4.5 µmol/L, rising significantly after 1 h (p < 0.05). Serum levels returned to baseline within 2 h. No significant differences were found regarding sex or diet. The shown pharmacokinetics can be used in future PA research.

Comparability of the LDH measurement and analysis based on external quality assessment.

Lactate dehydrogenase (LDH) is a critical enzyme widely used in clinical diagnostics. However, variations in measurement systems can lead to inconsistent results, potentially impacting clinical decision-making. This study aimed to evaluate the comparability of lactate dehydrogenase measurements by comparing routine methods with the IFCC reference method, and to analyze the standardization status of LDH testing through external quality assessment (EQA).. We analyzed 40 individual serum samples using four routine LD measurement systems: Siemens ADVIA 2400, Hitachi 7600/BioSino, Beckman AU5800, and Roche Cobas C501, alongside the IFCC reference method. The analytical quality specification (±6.4 %) was based on biological variation. Our study also included a comprehensive external quality assessment (EQA) program conducted by the Beijing Center for Clinical Laboratory (BCCL) over three years (2020, 2021, and 2023) to evaluate the consistency and reliability of LD measurements across different reagents. The acceptance limit is based on the requirement of desirable biological variability (±11.4 %). All four measurement systems showed strong correlations with the IFCC reference method (r ≥ 0.98). Relative average deviations ranged from -5.23 % to 3.71 %, within the acceptable biological variation limit. External quality assessment revealed high pass rates (94.7 %-98.7 %) across reagent groups, with significant improvements observed in some reagent groups from 2020 to 2023.. While the four LD measurement systems demonstrated good correlation with the IFCC reference method, some systems require further standardization. The study provides valuable insights into LD measurement accuracy and supports ongoing efforts to enhance laboratory testing comparability.

The Predictive Value of tPSA, fPSA, fPSA/tPSA Combined with Ultrasound Parameters in Postoperative Gleason Grading of Prostate Cancer.

Prostate cancer (PCa) is a common malignant tumor in men. This study aimed to explore the predictive value of serum biomarkers combined with ultrasound parameters for postoperative Gleason grading in PCa. This study included 65 PCa patients who underwent transurethral resection of the prostate in our hospital from January 2021 to December 2023. Based on postoperative Gleason grading, the study subjects were divided into a Mild Group (n = 34) and a Severe Group (n = 31). Levels of serological biomarkers such as total prostate-specific antigen (tPSA), free prostate-specific antigen (fPSA), and fPSA/tPSA (the ratio of fPSA to tPSA), along with ultrasound (US) parameters, including prostate-specific antigen density (PSAD), intraglandular prostate-specific antigen density (IGPSAD), extraglandular prostate-specific antigen density (EGPSAD), and US score were compared between the two groups to evaluate their predictive values for postoperative Gleason grading. The fPSA, tPSA, fPSA/tPSA ratio, PSAD, IGPSAD, EGPSAD, and US scores in the Severe Group were significantly different from those in the Mild Group (p < 0.05). The combined evaluation of fPSA, tPSA, fPSA/tPSA, PSAD, IGPSAD, EGPSAD, and US score for predicting postoperative Gleason grading in PCa patients revealed an area under the curve (AUC) of 0.947, indicating a better predictive performance. The AUC of multi-parameter union was significantly higher than that of individual parameters and serum indicators union (fPSA, tPSA and fPSA/tPSA) (p < 0.05). The combined use of multiple parameters (fPSA, tPSA, fPSA/tPSA, PSAD, IGPSAD, EGPSAD and US Score) shows better predictive performance than individual testing. The combined application has high predictive value in postoperative Gleason grading of PCa. These findings can effectively guide clinical decision-making and optimize diagnostic strategies for developing effective and targeted therapeutic interventions for PCa.

Mediating Effects of Serum Lipids and Physical Activity on Hypertension Management of Urban Elderly Residents in China.

Background/Objectives: Investigating the importance and potential causal effects of serum lipid biomarkers in the management of hypertension is vital, as these factors positively impact the prevention and control of cardiovascular disease (CVD). Methods: We surveyed 3373 urban residents using longitudinal data from the CHARLS database, collected between 2015 and 2020. Pearson correlation methods were employed to explore the relationships among the numerical variables. A logistic regression model was utilized to identify the risk factors for hypertension. The dose-effect relationship between serum lipids and BP was assessed using restricted cubic splines (RCS). Additionally, piecewise structural equation modeling (PiecewiseSEM) was conducted to further elucidate the direct and indirect pathways involving individual body indices, serum lipids, and PA on BP responses at different levels of physical activity (PA). Results: The four serum lipids showed significant differences between hypertensive and non-hypertensive residents (p < 0.05). All lipids, except for HDL cholesterol, demonstrated extremely significant positive correlations with both systolic blood pressure (SBP) and diastolic blood pressure (DBP) (p < 0.001). All serum lipid variables were significantly associated with the incidence of hypertension. Specifically, triglycerides (bl_tg), HDL (bl_hdl), and low-density lipoprotein LDL cholesterol were identified as significant risk factors, with odds ratios (ORs) of 1.56 (95% CI: 1.33-1.85, p < 0.001), 1.16 (95% CI: 1.02-1.33, p < 0.05), and 1.62 (95% CI: 1.23-2.15, p < 0.001), respectively. Conversely, cholesterol (bl_cho) was a protective factor for hypertension, with an OR of 0.60 (95% CI: 0.42-0.82, p < 0.01). PA showed weak relationships with blood pressure (BP); however, PA levels had significant effects, particularly at low PA levels. The four serum lipids had the most mediating effect on BP, especially under low PA level conditions, while PA exhibited a partly weak mediating effect on BP, particularly under high PA level conditions. Conclusions: Serum lipids have significant nonlinear relationships with BP and PA levels exert different influences on BP. The significant mediating effects of serum lipids and the weak mediating effects of PA on individual body indices related to SBP and DBP demonstrate significant differences across varying levels of PA, highlighting the importance of low PA levels in hypertension management. This study could provide valuable recommendations and guidance in these areas.

Genetic variation in the RETN promoter, accompanied by latent sarcopenic obesity, led to insulin resistance in a Japanese cohort: the Toon Genome Study.

Resistin, inducing insulin resistance, is elevated in the sera of individuals with the G-A haplotype at c.-420 C>G (rs1862513) and c.-358 G>A (rs3219175). This haplotype is associated with visceral obesity and low grip strength. To elucidate the hidden relationship between the G-A haplotype and insulin resistance, integration of specific phenotypes defined by body composition and 75 g OGTT would be a promising strategy. The 803 Japanese participants (average age: 62 years), attending annual medical checkups, were evaluated every 5 years. Participants were categorised by skeletal muscle mass, visceral fat score and OGTT results. Hierarchical clustering was performed using body composition and glucose metabolism parameters. Whole blood cells from participants homozygous for the G-A or C-G haplotype (n=25 and 33, respectively), matched for age, sex and BMI, using propensity score matching, were used for RNA-seq, pathway analysis and RT-PCR. Multivariate analysis showed that individuals with the G-A haplotype, when accompanied by latent skeletal muscle loss and visceral obesity (latent sarcopenic obesity), presented a pronounced deterioration in insulin resistance over a 5 year period. Cluster 2, identified using hierarchical clustering, was characterised by low skeletal muscle mass, visceral obesity and insulin resistance. This cluster, with the G-A haplotype, demonstrated deterioration in insulin resistance. RNA-seq and RT-PCR revealed altered expression of mitophagy-related genes in whole blood cells of the G-A homozygotes. The G-A haplotype, accompanied by latent low skeletal muscle mass and visceral obesity, led to the deterioration of insulin resistance over a 5 year period in this cohort, possibly through the altered expression of mitophagy-related genes.

Studying the impact of probiotic agents on the pathogenetic and clinical features of generalized periodontitis

Generalized periodontitis remains one of the most prevalent dental diseases, complications of which significantly deteriorate patients’ quality of life. Currently, the use of probiotic agents is considered a promising direction to enhance the effectiveness of non-surgical treatment of this pathology. Studying the impact of different probiotics on the pathogenetic and clinical features of generalized periodontitis will allow proposing optimized protocols for comprehensive treatment, reducing patient rehabilitation periods and improving the overall dental health of the population. The aim of this study is to examine the influence of various probiotic agents on the pathogenetic and clinical characteristics, treatment effectiveness of generalized periodontitis in adult patients by analyzing professional scientific literature. The literature review provides a brief overview of various probiotic groups and discusses pathogenetic mechanisms of their interaction with the microbiota of oral biofilms. The immunomodulatory mechanisms of probiotics on local and systemic immune responses in patients with generalized periodontitis, inhibition of enzymes responsible for bone tissue resorption, are presented. The analysis results of scientific sources regarding the dynamics of changes in clinical symptoms, microbiological, immunological, and biochemical parameters of saliva and blood serum in individuals with generalized periodontitis receiving comprehensive rehabilitation using probiotic agents compared to patients treated with traditional protocols are provided. The study highlights statistical differences in clinical and laboratory indicators of periodontitis progression at different treatment intervals. Conclusions. The use of probiotic agents for treating patients with generalized periodontitis significantly influences the clinical course of the disease by altering the species composition of dental biofilms and modulating local immune and inflammatory reactions. However, the known results of experimental and clinical studies often have conflicting findings regarding the efficacy of specific probiotic strains and the duration of inflammatory process stabilization over extended periods after treatment, which means a further study is required.

Spatial omics-based machine learning algorithms for the early detection of hepatocellular carcinoma

BackgroundWorldwide, hepatocellular carcinoma (HCC) is the second most lethal cancer, although early-stage HCC is amenable to curative treatment and can facilitate long-term survival. Early detection has proved difficult, as proteomics, transcriptomics, and genomics have been unable to discover suitable biomarkers.MethodsTo find new biomarkers of HCC, we utilized a spatial omics N-glycan imaging method to identify altered glycosylation in cancer tissue (n = 53) and in paired serum of individuals with HCC (n = 23). Glycoproteomics identified the glycoproteins carrying these N-glycan structures, and we utilized an antibody array-based glycan imaging method to examine all the N-glycans associated with the identified glycoproteins. N-glycans from the examined glycoproteins were used to create machine learning algorithms, which were tested in a case-control sample set of 100 patients with cirrhosis and HCC and 101 matched patients with cirrhosis alone.ResultsSpatial glycan imaging identifies thirteen branched, fucosylated, and high mannose glycans as altered in HCC tissue and in matched patient serum. Glycoproteomics identifies over 50 proteins containing these changes, of which sixteen glycoproteins were selected for further testing in an independent patient set. Algorithms using a combination of glycan and glycoproteins accurately differentiate early-stage and all HCC from cirrhosis with AUROC values of 0.88–0.97.ConclusionsIn conclusion, we present the development and application of a new biomarker platform, which can identify effective biomarkers for the early detection of HCC. This platform may also apply to other diseases, in which changes in N-linked glycosylation are known to occur.

Pristine NiMOF Sandwiched between 1D and 3D Engineered Au Particles and Dendrites for Ultraswift Folic Acid Sensing in Cellular Microenvironment.

Catalytic metal-organic frameworks (MOFs)-based sensor matrices can act synergistically with Au metallic nanostructures to generate amplified signal readouts by causing the electro-oxidation of the target analyte. Folic acid (FA), an essential water-soluble vitamin and a precursor for enzymes, requires timely and precise monitoring in the serum of individuals with varying clinical diagnoses. An attempt has been made in this direction through our work, where the rapid detection of FA through its oxidation at metal centers from hybrid nanomaterials is deployed for signal generation. A nonenzymatic, nonimmunometric approach involving a sandwich model, comprising NiMOF layered between gold nanoparticles (AuNPs) and gold nanodendrites (AuNDs) incorporated within a sensor matrix, has been deployed for this purpose. The probe displayed great analytical performance with a linear dynamic range (LDR) from 1 × 10-11 M to 1 × 10-3 M and a limit of detection (LOD) of 0.43 × 10-11 M. The probe's average response time with respect to changes in FA concentration was recorded as less than 2.1 s, making it a rapid sensing platform for FA detection. The real-life applicability of the developed sensor was tested in serum, followed by analysis in a breast cancer cellular microenvironment, which yielded a current recovery between 95.11 and 98.17%. The in vitro analysis was further validated through live-cell imaging using the standard method of fluorescence. The shorter fabrication time of the developed sensor compared to existing ones makes it a facile and efficient sensing platform for FA detection in clinical settings. This study represents the first report on the conjunction of 1D, 2D, and 3D materials as a sensing matrix for molecular detection applications.

Expression and Purification of ADAMTSL5 in E. coli and Validation of Activity in Psoriasis Serum.

A disintegrin and metalloprotease domain containing thrombospondin type 1 motif-like 5 (ADAMTSL5), a protein linked to psoriasis, was obtained by prokaryotic expression and purification for potential utilization as a new auxiliary diagnostic marker for psoriasis. It was subsequently applied in psoriasis research. The designed ADAMTSL5 gene was inserted into the pET-30a (+) vector and expressed in the BL21 (DE3) strain as a fusion protein. Following this, the recombinant ADAMTSL5 protein was purified using affinity chromatography. Purified ADAMTSL5, obtained in conjunction with magnetic beads, was directly employed in both psoriasis patients and healthy individuals. The results indicated that the molecular weight of the ADAMTSL5 protein obtained through prokaryotic expression and purification was approximately 27 kDa, with a protein concentration of 0.96 mg/mL. Analysis of anti-ADAMTSL5 levels in the serum of both psoriasis patients and healthy individuals using magnetic microparticle chemiluminescence demonstrated that anti-ADAMTSL5 levels in the serum of psoriasis patients surpassed those of healthy individuals, showing a significant difference with p < 0.001. The experimental findings presented here may contribute to the utilization of ADAMTSL5 as a marker for diagnosing psoriasis, offering novel insights and experimental avenues for further investigation.

Curcumin targets CXCL16-mediated podocyte injury and lipid accumulation in diabetic kidney disease treatment.

Among the complications of diabetes, diabetic kidney disease (DKD) frequently emerges, typified by the detrimental effects on renal function, manifesting through inflammation, dysregulated lipid metabolism, and harm to podocytes. Existing research underscores the significance of the soluble form of C-X-C chemokine ligand 16 (CXCL16) within the context of renal impairments. However, whether CXCL16 is involved in the pathogenesis of DKD remains elusive. We report that CXCL16 levels in the serum and kidneys of individuals with DKD were elevated and correlated with various lipid parameters. The expression of CXCL16 in human podocytes subjected to high glucose or palmitic acid induction and exogenous CXCL16 administration in these cells were examined. Higher CXCL16 levels were linked to abnormal lipid metabolism. Exogenous CXCL16 administration induced lipid droplets, microfilament disorganization, apoptosis, oxidative stress, and inflammation, inhibited PPAR γ,up-regulated COX2 expression, and inhibited Nrf2 translocation in podocytes. Molecular analysis revealed that Curcumin (Cur), a polyphenolic compound derived from Curcuma longa and an Nrf2 agonist, targets the ATP-binding pocket of CXCL16, inhibiting its kinase activity. Meanwhile, Cur therapy alleviated podocyte injury, lipid accumulation, improved glomerulopathy, and reduced albuminuria. Furthermore, after silencing CXCL16 expression in podocytes using siRNA, the effects of exogenous CXCL16 were nullified, and Cur no longer exhibited any significant impact. Thus, CXCL16 participates in the pathogenesis of DKD. Inhibition of CXCL16 has shown promising results in experimental models, suggesting its beneficial effects in ameliorating DKD.

The Value of Repeat 5-HIAA Measurements as a Predictor of Carcinoid Heart Disease: A Prospective 5-Year Follow-Up Study in Patients with Small Intestinal Neuroendocrine Tumors.

Background: Small intestinal neuroendocrine tumors (SI-NETs) are characterized by carcinoid syndrome and carcinoid heart disease (CHD). The aim of the present study was to identify early risk markers for carcinoid heart disease and survival in a prospective median-term follow-up setting. Methods: We measured 5-HIAA and cumulative 5-HIAA exposure (Cum-5-HIAA) based on repeated measurements, proBNP, vascular function, hepatic tumor load, and transthoracic echocardiography (TTE) at baseline and during the median 5-year follow-up. Of 65 patients with SI-NETs, 54 patients underwent a prospective follow-up. In addition, survival was evaluated during the median follow-up of 6 years. Results: At baseline, three patients had CHD. During the median follow-up of 5 years, two patients (4%) developed CHD. Cum-5-HIAA and proBNP correlated with CHD (Westberg score, Spearman's ρ = 0.32 and 0.31, respectively). Cum-5-HIAA had a superior diagnostic capability, predicting CHD in receiver operator characteristic analysis with an AUC of 0.98 (95% CI: 0.94-1.00) and outperformed proBNP, chromogranin A (CgA), and individual serum 5-HIAA measurements (AUC = 0.75, 0.85, and 0.91, respectively). Minor changes in valve regurgitation were frequently detected but did not correlate with vascular function. Regurgitation increased or decreased in 29% of tricuspid and 30% of pulmonic valves. CHD, hepatic tumor load, serum 5-HIAA, and elevated aortic pulse wave velocity (PWV) were associated with increased mortality in SI-NET patients. Conclusions: Cum-5-HIAA is a promising biomarker for CHD risk and outperformed other biomarkers. CHD and hepatic tumor load are the strongest predictors of mortality. PWV is a novel predictor of survival. The incidence of CHD was low among the SI-NET patients, probably reflecting successful treatment regimens.

Altered extracellular atp, adp, and amp hydrolysis in blood serum of sedentary individuals after an acute, strength, exercise session

Nucleotidases participate in the regulation of physiological and pathological events, such as inflammation and coagulation. Different types of physical exercise promote changes in purinergic signaling. In the present study, we investigated the activities of soluble nucleotidases in the blood serum of sedentary young male adults before and after a resistance exercise session. In addition, we evaluated how this type of exercise could influence the concentrations of adenine nucleotides in the blood serum. The individuals were submitted to a strength exercise session, consisting of 8 exercises. Blood samples were collected pre- and post-exercise, and serum was separated for analysis. Results showed increases in ATP, ADP, and AMP hydrolysis post-exercise, compared to pre-exercise values. Our results demonstrate that a resistance exercise session modifies ATP metabolism, being one more form of exercise that can positively influence cardiovascular and metabolic health.

Downregulation of miR-214 promotes dilated Cardiomyopathy Progression through PDE5A-Mediated cGMP regulation

Dilated cardiomyopathy (DCM) is a myocardial disorder resulting in a substantial decline in cardiac function and potentially leading to heart failure. This research combines bioinformatics analysis with empirical validation to explore the roles and mechanisms of miR-214 in DCM. Using the DEseq2 R package, a total of 125 differentially expressed circulating miRNAs (DE c-miRNAs) and 784 DE genes (DEGs) were identified. Cross-analysis between target genes of DE c-miRNAs and DEGs identified 124 common genes, and protein-protein interaction analysis of common genes identified 11 hub genes. Twelve DE c-miRNAs were further verified by quantifying their levels in the serum of DCM patients and healthy individuals. miR-214 levels were significantly decreased in serum from DCM patients, positively correlated with left ventricular ejection fraction and left ventricular fractional shortening. Further analysis showed that miR-214 directly targets and negatively regulates phosphodiesterase 5 A (PDE5A). Elevated PDE5A expression reduced cGMP levels; however, using sildenafil, a PDE5A inhibitor, reversed this effect, substantiating the regulatory mechanism of miR-214 on cGMP via PDE5A. These results provide new potential targets for the diagnosis and treatment of DCM.

Synthesis of Ti4+ modified COF-based polymer for efficient enrichment of phosphopeptides in colorectal cancer serum

In this study, we propose a Ti4+ modified COF-based polymers (COF-PA-Ti4+) with a facile synthesis method for efficient enrichment of phosphopeptides in colorectal cancer serum. Thanks to the abundant modification sites provided by radical polymerization on COF, as well as the excellent hydrophilicity of vinyl phosphate and the strong chelating ability of Ti4+, COF-PA-Ti4+ have superior performance on phosphopeptides enrichment. Employing COF-PA-Ti4+ as the enrichment material, the detection method exhibits high selectivity (1:1000), low detection limit (low as 0.005 fmol μL−1), high size-exclusion effect (1:10,000), excellent reusability (10 cycles), good recovery (98.7 ± 0.6 %), and loading capacity (50 mg g−1), with analysis performed via MALDI-TOF MS. Most importantly, after enriching phosphopeptides from the serum of colorectal cancer (CRC) patients and healthy individuals by COF-PA-Ti4+, we discovered significant differences in the phosphopeptides between the two groups, validating the feasibility of this approach. Taken together, these results confirm that COF-PA-Ti4+ has an outstanding contribution to the precise capture of phosphopeptides and provides an innovative approach for rapid diagnosis of early CRC.

The association between circulating short-chain fatty acids and blood pressure in Chinese elderly population

The gut microbiome primarily generates short-chain fatty acids (SCFAs) by fermenting dietary fibers. Though previous studies have linked SCFAs to blood pressure, there remains a lack of research on the relationship between SCFAs levels in the serum of elderly individuals and blood pressure. Based on this, we investigated the associations of serum SCFAs with blood pressure in Chinese older adults in a cross-sectional study. In this report, we recruited 1013 older adults over 60 years of age from June to September 2016 in Lu 'an City, China. Using Ultra High Performance Liquid Chromatography-Quadrupole-Exactive-Orbitrap-Mass Spectrometry (UHPLC-QE-Orbitrap MS), we measured the level of various SCFAs, including acetic acid (AA), propanoic acid (PA), butyric acid (BA), isobutyric acid (iso-BA), valeric acid (VA), isovaleric acid (iso-VA), and caproic acid (CA), in serum samples collected from Chinese elderly adults. The study recruited 1013 older adults in total. Multiple logistic regression analysis shows that AA (OR = 0.696, 95%CI: 0.501–0.966) and VA (OR = 0.713, 95%CI: 0.516–0.985) are negatively associated with hypertension. Linear regression analysis shows a negative correlation between AA (β = -3.89, 95% CI: -7.12 – -0.66) and the systolic blood pressure (SBP) levels, and a significant negative association between iso-VA (β = -2.11, 95% CI: -3.94 – -0.29) and diastolic blood pressure (DBP) levels. Whether in unadjusted or adjusted linear regression models, we all observe significant positive associations between CA and blood pressure levels. In the Bayesian kernel-machine regression (BKMR) models, the trends between the mixture of SCFAs and hypertension, SBP are inverse, but not significant; we also observe a significant negative correlation between AA and SBP, and a significant negative association between iso-VA and DBP levels, while CA is significantly positively correlated with SBP and DBP. Collectively, our results advocate for considering SCFA as a potential intervention to lower blood pressure, and especially AA may be a possible target for research. This may provide new perspectives for understanding the role of SCFAs in hypertension.