Senescence Biomarkers CKAP4 and PTX3 Stratify Severe Kidney Disease Patients.

INTRODUCTION: Cellular senescence is the irreversible growth arrest subsequent to oncogenic mutations, DNA damage, or metabolic insult. Senescence is associated with ageing and chronic age associated diseases such as cardiovascular disease and diabetes. The involvement of cellular senescence in acute kidney injury (AKI) and chronic kidney disease (CKD) is not fully understood. However, recent studies suggest that such patients have a higher-than-normal level of cellular senescence and accelerated ageing. METHODS: This study aimed to discover key biomarkers of senescence in AKI and CKD patients compared to other chronic ageing diseases in controls using OLINK proteomics. RESULTS: We show that senescence proteins CKAP4 (p-value < 0.0001) and PTX3 (p-value < 0.0001) are upregulated in AKI and CKD patients compared with controls with chronic diseases, suggesting the proteins may play a role in overall kidney disease development. CONCLUSIONS: CKAP4 was found to be differentially expressed in both AKI and CKD when compared to UHCs; hence, this biomarker could be a prognostic senescence biomarker of both AKI and CKD.

The effect of aerobic and high-intensity interval training on plasma pentraxin 3 and lipid parameters in overweight and obese women.

Background: It is unclear whether different exercise programs lead to an increase in the concentration of plasma Pentraxin3 (PTX3), an anti-inflammatory protein. This study aimed to investigate the effects of aerobic exercise (AE) and high-intensity interval training (HIIT) on plasma PTX3 levels in overweight and obese women. Method: A total of 45 sedentary women aged between 32.26 ± 6.30 voluntarily participated in the study. The control group (CG, n = 15) was selected among normal-weight women. Women in the group of participants who partook in exercise consisted of overweight and obese women according to a random method, including the AE group (n = 15) and the HIIT group (n = 15). The AE session conducted was 50 min in duration and consisted of warm-up exercises (5 min), and primary exercises (40 min, basic aerobic-step exercises). HIIT consists of warm-up exercises (5 min), primary exercises (work intervals: 6-10 × 1 min (80-90% HRmax), rest intervals: 1 min (walk, 50% HRmax), 21-29 min running. The exercises were applied for three sessions/week for 12 weeks. Fasting blood samples were taken from all participants before and after exercise and their body composition was measured. Results: As a result of two different 12-week exercises, serum PTX3 levels increased significantly by 47.53% in the AE group and 50.21% in the HIIT group (p < 0.01). It was determined that the mean PTX3 before and after exercise increased from 1.71 ± 0.43 to 2.47 ± 0.40 ng/dL and HIIT from 1.62 ± 0.39 to 2.31 ± 0.33 ng/dL. A significant decrease in body mass index (BMI) values were detected, approximately 5.81% in the AE group and 5.06% in the HIIT group (p < .01). A significant decrease was detected in glucose, insulin, HOMA-IR, LDL-C, and hsCRP whereas HDL-C and VO2max value increased significantly in both exercise groups (p < .05; p < .01). There were no significant differences in TG and TC levels between groups (p > .05). Also, no significant differences were found between the two types of exercises in terms of parameters. A significant negative correlation in the total sample was found between PTX3 with BMI, fat mass, LDL-C, and hsCRP. Conclusion: The percentage change in PTX3 values was not different between exercise types, whereas PTX3 was increased with exercise, regardless of the type of exercise. It can be said that both aerobic and HIIT increase PTX3, VO2max levels and improve lipid metabolism in overweight and obese women.

The assessment of pentraxin 3: a diagnostic and prognostic biomarker in lower respiratory tract infections in children.

BACKGROUND: Pentraxin 3 (PTX3) is an acute-phase reactant that is elevated in the plasma during inflammatory responses. We aimed to evaluate the utility of PTX3 as a clinical marker in children with lower respiratory tract infections (LRTIs) and the association between PTX3 and LRTIs severity. METHODS: We included 60 patients admitted to Fayoum University Hospital with LRTIs fulfilling the WHO criteria for diagnosing LRTIs. We collected data on peak temperature, respiratory rate, heart rate, oxygen saturation upon admission, and length of hospital stay. The complete blood count (CBC), C-reactive protein (CRP) level, and PTX3 were measured upon admission. RESULTS: PTX3 levels were significantly correlated with peak temperature, duration of hospital stay, the Pediatric Respiratory Severity Score (PRESS), total leucocytic count (TLC), CRP, and blood cultures. CONCLUSION: PTX-3 represented the severity of the disease and predicted the prognosis. Pentraxin levels demonstrate a statistically significant sensitivity of (93.3%) and a specificity of (70%) at the cut-off value (of 8.84) with an area under the curve (90.7%) in the diagnosis of LRTIs.

Pentraxin-3 (PTX-3) as a potential biomarker for predicting death in hospitalized patients with COVID-19.

BACKGROUND: Pentraxin 3 (PTX3) is an acute-phase protein that belongs to the pentraxin family, which plays an important role in the body's defense against pathogens. PTX3 levels have been associated with inflammatory processes, and it is a possible biomarker for the diagnosis and prognosis of different infectious diseases, including COVID-19. The objective of this study was to analyze the potential of PTX3 as a plasma biomarker for predicting death in patients hospitalized with COVID-19. METHODS: The study included a total of 312 patients with COVID-19, admitted from July 2020 to August 2021 to hospital ward and intensive care unit beds at two hospitals in the Northeast Region of Brazil. PTX3 was measured using ELISA in samples collected within 24 h after hospital admission. Maximally selected rank statistics were used to determine the PTX3 cutoff point that best distinguished patients who died from those who survived. A receiver operating characteristic (ROC) curve was used to determine the performance of the biomarker. Survival analysis was performed using a Kaplan-Meier curve, and a Cox regression model was used to determine predictors associated with death. RESULTS: Of the 312 patients included in the study, 233 recovered and 79 died. Patients who died had higher PTX3 levels at the time of admission, when compared to those who recovered (median: 52.84 versus 10.79 ng/mL; p < 0.001). PTX3 showed area under the ROC (AUC) = 0.834, higher than other markers used in clinical practice, such as C-reactive protein (AUC = 0.72) and D-dimer (AUC = 0.77). Furthermore, according to the Kaplan-Meier survival curve, patients with PTX3 concentrations above the cutoff point (27.3 ng/mL) had a lower survival rate (p = 0.014). In multivariate Cox regression, PTX3 > 27.3 ng/mL was an important predictor of death, regardless of other confounding factors (hazard ratio = 1.79; p = 0.027). CONCLUSION: PTX3 can be considered as a potential biomarker for predicting death in patients hospitalized with COVID-19.

Modulation of diabetes-related retinal pathophysiology by PTX3.

Diabetic retinopathy (DR) is a common complication of diabetes characterized by vascular pathology and neuroinflammation. Pentraxin 3 (PTX3) is a soluble pattern recognition molecule that functions at the crossroads between innate immunity, inflammation, and tissue remodeling. DR is known to involve inflammatory pathways, although the potential relevance of PTX3 has not been explored. We found that PTX3 protein levels increased in the retina of diabetic mice. Similarly, evaluation of a publicly available transcriptomic human dataset revealed increased PTX3 expression in DR with diabetic macular edema and proliferative retinopathy, when compared to nondiabetic retinas or diabetic retinas without complications. To further understand the role of PTX3 within DR, we employed the streptozotocin-induced diabetes model in PTX3 knockout mice (PTX3KO), which were followed up for 9 mo to evaluate hallmarks of disease progression. In diabetic PTX3KO mice, we observed decreased reactive gliosis, diminished microglia activation, and reduced vasodegeneration, when compared to diabetic PTX3 wild-type littermates. The decrease in DR-associated pathological features in PTX3KO retinas translated into preserved visual function, as evidenced by improved optokinetic response, restored b-wave amplitude in electroretinograms, and attenuated neurodegeneration. We showed that PTX3 induced an inflammatory phenotype in human retinal macroglia, characterized by GFAP upregulation and increased secretion of IL6 and PAI-1. We confirmed that PTX3 was required for TNF-α-induced reactive gliosis, as PTX3KO retinal explants did not up-regulate GFAP in response to TNF-α. This study reveals a unique role for PTX3 as an enhancer of sterile inflammation in DR, which drives pathogenesis and ultimately visual impairment.

Pentraxin 3 mediates inflammation and adipogenesis in Graves' orbitopathy pathogenesis.

Pentraxin 3 (PTX3) is a prototypic humoral soluble pattern-recognition molecule known to function in immunity-related inflammation. Given the lack of information on the precise functions of PTX3 in the pathogenesis of Graves' orbitopathy (GO), this study investigated the role of PTX3 in the inflammation and adipogenesis mechanisms of GO. We first compared the PTX3 expression between orbital tissues from patients with GO and normal controls using real-time PCR, which estimated significantly higher PTX3 transcript levels in the GO tissues than in the normal tissues. In addition, PTX3 production was markedly increased upon interleukin (IL)-1ß and adipogenic stimulation. We then evaluated the effects of silencing PTX3 in primary orbital fibroblast cultures by analyzing the expression levels of pro-inflammatory cytokines, adipogenesis-related proteins, and downstream transcription factors in cells transfected with or without small interfering RNA against PTX3, using western blot. Silencing PTX3 attenuated the IL-1ß-induced secretion of pro-inflammatory cytokines, including IL-6, IL-8, monocyte chemotactic protein-1, intercellular adhesion molecule-1, and cyclooxygenase-2, and suppressed the IL-1ß-mediated activation of p38 kinase, nuclear factor-κB, and extracellular signal-regulated kinase. Moreover, PTX3 knockdown suppressed adipogenic differentiation, as assessed using Oil Red O staining, as well as the expression of adipogenesis-associated transcription factors including peroxisome proliferator-activated receptor-γ, CCAAT/enhancer-binding proteins α and ß, adipocyte protein 2, adiponectin, and leptin. Thus, this study suggests that PTX3 plays a significant role in the pathogenesis of GO and may serve as a novel therapeutic target for the condition.

Plasma concentrations of IL-6, MIP-1ß, IP-10, and PTX-3 as predictors of the immunological response to antiretroviral treatment in people with HIV.

Despite effective antiretroviral therapy (ART), 15-30% of people with HIV experience poor CD4+ T-cell recovery, termed immunologic non-responders (INR). This study aims to evaluate whether pre-ART plasma levels of interleukin-6 (IL-6), interferon gamma-induced protein-10 (IP-10), macrophage inflammatory protein-1-ß (MIP-1ß), and/or pentraxin-3 (PTX-3) could predict subsequent immunologic recovery. Seventy-four participants were enrolled and classified as INR and immunologic responders (IR) based on CD4+/CD8+ ratio increase over 24 months after starting ART. The results showed no significant differences in cytokine levels between INR and IR. Therefore, IL-6, IP-10, MIP-1ß, and PTX-3 were unsuitable as predictive markers of poor immune recovery.

Unique hyaluronan structure of expanded oocyte-cumulus extracellular matrix in ovarian follicles.

In preovulatory follicles, after the endogenous gonadotropin surge, the oocyte-cumulus complexes (OCCs) produce hyaluronan (HA) in a process called "cumulus expansion". During this process, the heavy chains (HCs) of the serum-derived inter-alpha-trypsin inhibitor (IαI) family bind covalently to synthesized HA and form a unique structure of the expanded cumulus HA-rich extracellular matrix. Understanding the biochemical mechanism of the covalent linkage between HA and the HCs of the IαI family is one of the most significant discoveries in reproductive biology, since it explains basis of the cumulus expansion process running in parallel with the oocyte maturation, both essential for ovulation. Two recent studies have supported the above-mentioned findings: in the first, seven components of the extracellular matrix were detected by proteomic, evolutionary, and experimental analyses, and in the second, the essential role of serum in the process of cumulus expansion in vitro was confirmed. We have previously demonstrated the formation of unique structure of the covalent linkage of HA to HCs of IαI in the expanded gonadotropin-stimulated OCC, as well as interactions with several proteins produced by the cumulus cells: tumor necrosis factor-alpha-induced protein 6, pentraxin 3, and versican. Importantly, deletion of these genes in the mice produces female infertility due to defects in the oocyte-cumulus structure.

Interplay between host humoral pattern recognition molecules controls undue immune responses against Aspergillus fumigatus.

Pentraxin 3 (PTX3), a long pentraxin and a humoral pattern recognition molecule (PRM), has been demonstrated to be protective against Aspergillus fumigatus, an airborne human fungal pathogen. We explored its mode of interaction with A. fumigatus, and the resulting implications in the host immune response. Here, we demonstrate that PTX3 interacts with A. fumigatus in a morphotype-dependent manner: (a) it recognizes germinating conidia through galactosaminogalactan, a surface exposed cell wall polysaccharide of A. fumigatus, (b) in dormant conidia, surface proteins serve as weak PTX3 ligands, and (c) surfactant protein D (SP-D) and the complement proteins C1q and C3b, the other humoral PRMs, enhance the interaction of PTX3 with dormant conidia. SP-D, C3b or C1q opsonized conidia stimulated human primary immune cells to release pro-inflammatory cytokines and chemokines. However, subsequent binding of PTX3 to SP-D, C1q or C3b opsonized conidia significantly decreased the production of pro-inflammatory cytokines/chemokines. PTX3 opsonized germinating conidia also significantly lowered the production of pro-inflammatory cytokines/chemokines while increasing IL-10 (an anti-inflammatory cytokine) released by immune cells when compared to the unopsonized counterpart. Overall, our study demonstrates that PTX3 recognizes A. fumigatus either directly or by interplaying with other humoral PRMs, thereby restraining detrimental inflammation. Moreover, PTX3 levels were significantly higher in the serum of patients with invasive pulmonary aspergillosis (IPA) and COVID-19-associated pulmonary aspergillosis (CAPA), supporting previous observations in IPA patients, and suggesting that it could be a potential panel-biomarker for these pathological conditions caused by A. fumigatus.

Functional variants of the pentraxin 3 gene are associated with the metastasis and progression of prostate cancer.

Age, ethnic background and genetic components have been identified as the established risks for prostate cancer (PCa). Pentraxin 3 (PTX3), originally identified as a pattern-recognition molecule for defence against infectious agents, has multiple functions in tissue repair and in the regulation of cancer-associated inflammation. In this study, we sought to investigate the impact of PTX3 gene variants on the development of PCa. Genotypes of four common single-nucleotide polymorphisms (SNPs) of PTX3 gene, including rs1840680, rs2305619, rs3816527 and rs2120243, were profiled among 705 PCa patients and 705 ethnicity-matched controls. In this study, we found that patients who carry at least one minor allele (C) of rs3816527 (AC and CC) tended to develop advanced forms of diseases (clinical large T stage, OR, 1.593, p = 0.032; pathologically-confirmed nodal spread, OR, 1.987, p = 0.011; metastatic tumour, OR, 3.896, p = 0.032) as compared with those homologous for the major allele (AA). Further stratification analysis showed that such association of rs3816527 with lymphatic and distal metastasis of PCa was accentuated in the younger age group (≤65 at diagnosis) but not seen in the older age group (>65 at diagnosis), suggesting an age-specific effect of PTX3 variants. Prediction of PTX3 protein structure implied that polymorphism may alter the quaternary organization and oligomerization of PTX3 protein. Moreover, our gene silencing experiments and survey of public datasets revealed that elevation of PTX3 levels in PCa was required for cell migration and associated with tumour metastasis. Our results highlight an association of PTX3 rs3816527 with the progression of PCa.

Genetic evidence for serum amyloid P component as a drug target in neurodegenerative disorders.

The mechanisms responsible for neuronal death causing cognitive loss in Alzheimer's disease (AD) and many other dementias are not known. Serum amyloid P component (SAP) is a constitutive plasma protein, which is cytotoxic for cerebral neurones and also promotes formation and persistence of cerebral Aß amyloid and neurofibrillary tangles. Circulating SAP, which is produced exclusively by the liver, is normally almost completely excluded from the brain. Conditions increasing brain exposure to SAP increase dementia risk, consistent with a causative role in neurodegeneration. Furthermore, neocortex content of SAP is strongly and independently associated with dementia at death. Here, seeking genomic evidence for a causal link of SAP with neurodegeneration, we meta-analysed three genome-wide association studies of 44 288 participants, then conducted cis-Mendelian randomization assessment of associations with neurodegenerative diseases. Higher genetically instrumented plasma SAP concentrations were associated with AD (odds ratio 1.07, 95% confidence interval (CI) 1.02; 1.11, p = 1.8 × 10-3), Lewy body dementia (odds ratio 1.37, 95%CI 1.19; 1.59, p = 1.5 × 10-5) and plasma tau concentration (0.06 log2(ng l-1) 95%CI 0.03; 0.08, p = 4.55 × 10-6). These genetic findings are consistent with neuropathogenicity of SAP. Depletion of SAP from the blood and the brain, by the safe, well tolerated, experimental drug miridesap may thus be neuroprotective.

Can Vitamin D Reduce Inflammation? The Influence of Supplementation on Selected Immunological Markers.

There is increasing evidence that vitamin D (VitD) supplementation may reduce inflammation in individuals with multiple sclerosis (MS). The aim of this study was to evaluate the effect of different doses of VitD on selected markers of inflammation in patients with relapsing-remitting MS (RRMS). Participants were divided depending on the supplemented dose of VitD into a high-dose (2000 IU/d; HD) group and a low-dose (15,960 IU/month; LD) group (n = 23 and n = 29, respectively). The concentration of 25(OH)D and the levels of CXCL16, PTX3, ALCAM, IL-1RA, and OPG were measured initially and after six months of VitD supplementation in blood serum. A significant increase in the concentrations of CXCL16, PTX3, and OPG was observed during the study (p = 0.02, p = 0.01, and p < 0.01, respectively). Furthermore, a higher increase in PTX3 and OPG in the LD group was observed (p = 0.04 and p = 0.03, respectively). A significant positive correlation was observed between the 25(OH)D serum concentration and PTX3 (R = 0.28, p < 0.05) and OPG (R = 0.28, p < 0.05) only at the beginning of the study. In patients with RRMS, such doses of VitD might be too low to induce obvious beneficial effects on the pro-inflammatory and inflammatory balance.

PTX3 promotes cementum formation and cementoblast differentiation via HA/ITGB1/FAK/YAP1 signaling pathway.

Cementum is a vital component of periodontium, yet its regeneration remains a challenge. Pentraxin 3 (PTX3) is a multifunctional glycoprotein involved in extracellular matrix remodeling and bone metabolism regulation. However, the role of PTX3 in cementum formation and cementoblast differentiation has not been elucidated. In this study, we initially observed an increase in PTX3 expression during cementum formation and cementoblast differentiation. Then, overexpression of PTX3 significantly enhanced the differentiation ability of cementoblasts. While conversely, PTX3 knockdown exerted an inhibitory effect. Moreover, in Ptx3-deficient mice, we found that cementum formation was hampered. Furthermore, we confirmed the presence of PTX3 within the hyaluronan (HA) matrix, thereby activating the ITGB1/FAK/YAP1 signaling pathway. Notably, inhibiting any component of this signaling pathway partially reduced the ability of PTX3 to promote cementoblast differentiation. In conclusion, our study indicated that PTX3 promotes cementum formation and cementoblast differentiation, which is partially dependent on the HA/ITGB1/FAK/YAP1 signaling pathway. This research will contribute to our understanding of cementum regeneration after destruction.

Validating genetic variants in innate immunity linked to infectious events in acute myeloid leukemia post-induction chemotherapy.

Infectious events, such as sepsis and invasive fungal disease (IFD), pose significant risks in patients with acute myeloid leukemia (AML). Previous studies, including our own, have suggested a potential role of single nucleotide polymorphisms (SNPs) within the innate immune system in influencing individual infection susceptibility. However, many of these associations lack validation in independent cohorts. This study sought to validate the impact of 11 candidate SNPs across 6 genes (TLR2, TLR4, Dectin-1, DC-SIGN, PTX3, L-Ficolin) in an independent cohort of patients. Two cohorts with newly diagnosed AML patients receiving intensive induction chemotherapy were analyzed: a stratification cohort comprising 186 patients and a validation cohort consisting of 138 patients. Multiple SNPs in each cohort were found to be associated to infectious complications, notably the DC-SIGN SNP rs4804800 demonstrated a significant association with sepsis in both cohorts. SNPs within the PTX3 and Dectin-1 genes were linked to IFD development in one cohort each. This study represents the first validation study of candidate genes associated with infectious events in AML patients after intensive induction chemotherapy. Identifying genetic predispositions to infections could significantly impact the management of antimicrobial prophylaxis and treatment in AML patients.

The impact of obesity, age, and gender on plasmatic levels of selected glycoprotein biomarkers and miRNA-499 in OSA patients.

BACKGROUND: The current obstructive sleep apnea (OSA) diagnostic uses polysomnography or limited polygraphy and requires specialized personnel and technical equipment. Glycoprotein biomarkers and microRNAs are being explored as a possible new method for screening. We aimed to evaluate whether certain biomarkers and microRNA, previously identified as related to OSA, could be influenced by factors such as gender, age, and obesity level in patients with OSA. METHODS: In this retrospective analytical study, patients with moderate to severe OSA (n = 130) were compared with the control group. Serum levels of selected biomarkers and microRNA were taken from both groups. The group of OSA patients was then stratified by gender, obesity level, and age to see the possible influence of those variables on biomarker levels. RESULTS: Levels of all studied biomarkers - C-reactive protein (CRP), high-sensitivity troponin I (hsTnI), pentraxin-3 (PTX-3), and microRNA-499 were significantly higher in patients with OSA compared to the control group. In the OSA group only hsTnI showed a statistically significant relationship with gender. Levels of CRP and hsTnI showed a significant dependence on the level of obesity. Dependency on age was proven for hsTnI. CRP, PTX-3, and microRNA-499 did not have any statistically significant relationship with age. CONCLUSION: We found that serum levels of pentraxin-3 and microRNA-499 in patients with moderate to severe obstructive sleep apnoea are independent of gender, obesity, and age. CRP was affected by the level of obesity and hsTnI was influenced by all 3 variables. We consider these findings important for further research of OSA biomarkers.

Longitudinal soluble marker profiles reveal strong association between cytokine storms resulting from macrophage activation and disease severity in COVID-19 disease.

SARS-CoV2 infection results in a range of disease severities, but the underlying differential pathogenesis is still not completely understood. At presentation it remains difficult to estimate and predict severity, in particular, identify individuals at greatest risk of progression towards the most severe disease-states. Here we used advanced models with circulating serum analytes as variables in combination with daily assessment of disease severity using the SCODA-score, not only at single time points but also during the course of disease, to correlate analyte levels and disease severity. We identified a remarkably strong pro-inflammatory cytokine/chemokine profile with high levels for sCD163, CCL20, HGF, CHintinase3like1 and Pentraxin3 in serum which correlated with COVID-19 disease severity and overall outcome. Although precise analyte levels differed, resulting biomarker profiles were highly similar at early and late disease stages, and even during convalescence similar biomarkers were elevated and further included CXCL3, CXCL6 and Osteopontin. Taken together, strong pro-inflammatory marker profiles were identified in patients with COVID-19 disease which correlated with overall outcome and disease severity.

Influence of Dulaglutide on Serum Biomarkers of Atherosclerotic Plaque Instability: An Interventional Analysis of Cytokine Profiles in Diabetic Subjects-A Pilot Study.

Background and Objectives: The rise in global diabetes cases, reaching a staggering 529 million in 2021 from 108 million in 1980, underscores the urgency of addressing its complications, notably macrovascular ones like coronary artery, cerebrovascular, and peripheral artery diseases, which contribute to over 50% of diabetes mortality. Atherosclerosis, linked to hyperglycemia-induced endothelial dysfunction, is pivotal in cardiovascular disease development. Cytokines, including pentraxin 3 (PTX3), copeptin, lipoprotein(a) [Lp(a)], and matrix metalloproteinase-9 (MMP-9), influence atherosclerosis progression and plaque vulnerability. Inhibiting atherosclerosis progression is crucial, especially in diabetic individuals. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), increasingly used for type 2 diabetes, show promise in reducing the cardiovascular risk, sparking interest in their effects on atherogenesis. This study sought to examine the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on biomarkers that indicate the instability of atherosclerotic plaques. These biomarkers include pentraxin 3 (PTX3), copeptin (CPC), matrix metalloproteinase-9 (MMP-9), and lipoprotein(a) [Lp(a)]. Materials and Methods: A total of 34 participants, ranging in age from 41 to 81 years (with an average age of 61), who had been diagnosed with type 2 diabetes mellitus (with a median HbA1c level of 8.8%), dyslipidemia, and verified atherosclerosis using B-mode ultrasonography, were included in the study. All subjects were eligible to initiate treatment with a GLP-1 RA-dulaglutide. Results: Significant reductions in anthropometric parameters, blood pressure, fasting glucose levels, and HbA1c levels were observed posttreatment. Moreover, a notable decrease in biochemical markers associated with atherosclerotic plaque instability, particularly PTX3 and MMP-9 (p < 0.001), as well as Lp(a) (p < 0.05), was evident following the GLP-1 RA intervention. Conclusions: These findings underscore the potential of GLP-1 RAs in mitigating atherosclerosis progression and plaque vulnerability, thus enhancing cardiovascular outcomes in individuals with type 2 diabetes mellitus.

Effects of a medium cut-off dialyzer on inflammation and cardiac and vascular function in hemodialysis patients with heart failure.

INTRODUCTION: Expanded hemodialysis (HDx) could provide clearance of larger middle-molecule uremic toxins. We compared the effect of hemodialysis with medium cut-off membranes and high-flux (HFHD) membranes regarding changes in inflammation and vascular and left ventricular function. METHODS: This was a single-center, prospective, parallel-group comparative study. Patients were divided into two groups (HDx: 25 patients and HFHD: 26 patients). All measurements were performed at baseline and 12 weeks. Serum c-reactive protein, interkelukin-18, pentraxin-3, ß-2 microglobulin, and brain natriuretic peptide were measured. We used pulse wave velocity and augmentation index to assess arterial stiffness and echocardiography to evaluate left and right ventricular function. FINDINGS: We enrolled 51 patients. Although serum c-reactive protein, interkelukin-18, pentraxin 3, and ß-2 microglobulin were significantly decreased in the HDx group (p = 0.02, p < 0.001, p = 0.002, and p = 0.02, respectively), there was no significant change in HFHD group at 12th week. Serum c-reactive protein and interkelukin-18were significantly lower in the HDx group compared to the HFHD group in the 12th week (p = 0.007 and p = 0.03, respectively). We observed a significant decrease in pulse wave velocity in the HDx group at the end of the study (p = 0.03). Although there was no significant change in pulse wave velocity in the HFHD group, pulse wave velocity was similar between the HDx and HFHD groups in the 12th week. We detected a significant decrease in the mean isovolumetric relaxation time in the HDx group (p = 0.006). However, there was no significant difference in isovolumetric relaxation time between the HDx and HFHD groups in the 12th week. DISCUSSION: HDx provides better clearance of middle molecular uremic toxins and inflammatory biomarkers, and it may be associated with better central hemodynamic parameters and diastolic functions.

Synergistic impact of innate immunity hyper-activation and endothelial dysfunction on the magnitude of organ failure in the infection-sepsis continuum.

OBJECTIVES: Identifying host response biomarkers implicated in the emergence of organ failure during infection is key to improving the early detection of this complication. METHODS: Twenty biomarkers of innate immunity, T-cell response, endothelial dysfunction, coagulation, and immunosuppression were profiled in 180 surgical patients with infections of diverse severity (IDS) and 53 with no infection (nIDS). Those better differentiating IDS/nIDS in the area under the curve were combined to test their association with the sequential organ failure assessment score by linear regression analysis in IDS. Results were validated in another IDS cohort of 174 patients. RESULTS: C-reactive protein, procalcitonin, pentraxin-3, lipocalin-2 (LCN2), tumoral necrosis factor-α, angiopoietin-2, triggering receptor expressed on myeloid cells-1 (TREM-1) and interleukin (IL)-15 yielded an area under the curve ≥0.75 to differentiate IDS from nIDS. The combination of LCN2, IL-15, TREM-1, angiopoietin-2 (Dys-4) showed the strongest association with sequential organ failure assessment score in IDS (adjusted regression coefficient; standard error; P): Dys-4 (3.55;0.44; <0.001), LCN2 (2.24; 0.28; <0.001), angiopoietin-2 (1.92; 0.33; <0.001), IL-15 (1.78; 0.40; <0.001), TREM-1(1.74; 0.46; <0.001), tumoral necrosis factor-α (1.60; 0.31; <0.001), pentraxin-3 (1.12; 0.18; <0.001), procalcitonin (0.85; 0.12; <0.001). Dys-4 provided similar results in the validation cohort. CONCLUSIONS: There is a synergistic impact of innate immunity hyper-activation (LCN2, IL-15, TREM-1) and endothelial dysfunction (angiopoietin-2) on the magnitude of organ failure during infection.