A study of granulysin and pentraxin 3 genetic polymorphisms and their contribution to acne susceptibility.

This study aims to examine the genetic polymorphisms of the granulysin (GNLY) and pentraxin 3 (PTX3) genes and their association with acne in Egypt. Acne vulgaris is classified as a disorder of the pilosebaceous unit. Clinical, histological, and immunological findings indicate that inflammation is involved in every stage of acne development. GNLY and PTX3 are both involved in the body's immune system and may play a role in the pathophysiology of acne. This case-control study included 180 participants who have acne and 180 healthy controls. Real-time PCR was used to genotype GNLY rs7908 and PTX3 rs2305619 polymorphisms. Genotype occurrence and allelic spreading for both single nucleotide polymorphisms (SNP) are in Hardy-Weinberg equilibrium. Regarding rs7908, no statistical difference was observed in the genotype and allele distributions between acne patients and controls. On the other hand, rs2305619 showed a statistical difference in the genotype and allele distributions between acne patients and controls, with a marked prevalence of the GG group and G allele in acne patients. Our study revealed a significant link between the PTX3 rs2305619 and acne susceptibility in Egypt, with the AG + GG genotype strongly predicting acne. In contrast, the GNYL rs7908 polymorphism was not associated with acne. These results highlight a genetic component to acne and suggest that PTX3 rs2305619 could be a key marker for understanding acne susceptibility.

Involvement of pentraxin-3 in the development of hypertension but not left ventricular hypertrophy in male spontaneously hypertensive rats.

Hypertension drives the development of concentric left ventricular hypertrophy (LVH). However, the relative contribution of pentraxin-3 (PTX-3), a novel marker for inflammatory cardiovascular disease, in the hypertrophic response to pressure overload has not been adequately elucidated. We investigated the role of PTX-3 in the development of LVH in spontaneously hypertensive rats (SHR), untreated and treated with either captopril (an ACE inhibitor) or hydralazine (a non-specific vasodilator). Three-month-old SHR received either 20 mg/kg/day hydralazine (SHR + H, n = 6), 40 mg/kg/day captopril (SHR + C, n = 6), or plain gelatine cubes (untreated SHR, n = 7) orally for 4 months. Wistar Kyoto rats (WKY, n = 7) were used as the normotensive controls. Blood pressure (BP) was measured using the tail-cuff method. Cardiac geometry and function were determined using M-mode echocardiography. Circulating concentrations of inflammatory markers were measured in plasma by ELISA. LV fibrosis and cardiomyocyte width were assessed by histology. Relative mRNA expression of PTX-3 was determined in the LV by RT-PCR. Untreated SHR exhibited greater systolic BP and relative wall thickness (RWT) compared to WKY. Captopril and hydralazine normalized BP but only captopril reversed RWT in SHR. Circulating PTX-3 and VCAM-1 levels were elevated in untreated SHR and reduced with captopril and hydralazine. Circulating PTX-3 was positively associated with systolic BP but lacked independent relations with indices of LVH. LV relative mRNA expression of PTX-3 was similar between the groups. PTX-3 may not be involved in the development of LVH in SHR, but plausibly reflects the localized inflammatory milieu associated with hypertension.

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.

Presence of heavy chain-hyaluronan/pentraxin 3 (HC-HA/PTX3) complex in human umbilical cord.

The heavy chain (HC)-hyaluronan (HA)/pentraxin 3 (HC-HA/PTX3) complex is formed by tumor necrosis factor-stimulated gene-6 (TSG-6) catalyzing the covalent (ester bond) transfer of HC1 from inter-α-trypsin inhibitor (IαI) to HA followed by tight binding of PTX3. The presence of such a complex has been found in human amniotic membrane (AM) and is considered to be a major matrix component responsible for its anti­inflammatory and anti­scarring properties to promote regenerative healing. Because the therapeutic potentials of AM and umbilical cord (UC) are similar, we herein evaluated whether human UC also contains HC-HA/PTX3. Immunostaining of UC cross-sections showed abundant PTX3, HC1, HA, TSG-6, and bikunin. Western blot analysis suggested the presence of HC1 complex bound via a NaOH-sensitive bond and tightly bound to PTX3 multimer in UC and AM extracts but not in chorion and placenta extracts. HC-HA/PTX3 was purified from UC extract by successive runs of density gradient ultracentrifugation and verified the presence of HC1 but not HC2 or HC3 based on western blot analysis. These results suggest the presence of HC-HA/PTX3 complex in UC is similar to AM.

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.

Pediatric nephrotic syndrome: The interplay of oxidative stress and inflammation.

Background: The pathophysiological mechanisms crucial in the development of nephrotic syndrome (NS) in the pediatric population are still not fully understood. This study aimed to investigate the relationship between hypertension, oxidative stress, and inflammation in pediatric patients during the acute phase of the disease. Methods: The study included 33 children, aged 2 to 9 years, with nephrotic syndrome. Blood samples were collected during the acute phase and remission. Parameters of oxidative status were determined, including total oxidative status (TOS), advanced oxidation protein products (AOPP), prooxidant-antioxidant balance (PAB), sulfhydryl groups (-SH), paraoxonase 1 (PON1), and total antioxidant status (TAS) in serum, measured spectrophotometrically. Inflam - matory parameters such as pentraxin 3 (PTX3), leptin, program med cell death ligand 1 (PD-L1), and E-cadherin were determined using enzyme-linked immunosorbent assay (ELISA). Results: Patients with nephrotic syndrome and hypertension had significantly higher levels of advanced oxidation protein products and total antioxidant status (p=0.029 and p=0.003, respectively). During the acute phase of the disease, lower activity of sulfhydryl groups and paraoxonase 1 was observed compared to remission (p<0.001, for both). Pentraxin 3 levels were higher, while leptin levels were lower during the acute phase (p<0.001, for both). Pentraxin 3 correlated with advanced oxidation protein products and total antioxidant status during the acute phase but not in remission (rs=0.42, p=0.027 and rs=0.43, p=0.025, respectively). A negative correlation between Advanced oxidation protein products and leptin was observed during the acute phase, which disappeared in remission (rs=-0.42, p=0.028). Conclusions: Results of this study show that hypertension influences oxidative stress markers, and decreased antioxidant capacity may contribute to nephrotic syndrome development. Pentraxin 3 appears as a potential disease activity marker, indicating a dynamic connection between inflammation and oxidative stress. Leptin may also play a role in oxidative stress in nephrotic syndrome.

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.

The Impact of Pentraxin 3 Serum Levels and Angiotensin-Converting Enzyme Polymorphism on Pulmonary Infiltrates and Mortality in COVID-19 Patients.

OBJECTIVES: The aim of this study was to examine the impact of the pentraxin 3 (PTX3) serum level and angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism on the severity of radiographic pulmonary infiltrates and the clinical outcomes of COVID-19. METHODS: The severity of COVID-19 pulmonary infiltrates was evaluated within a week of admission by analyzing chest X-rays (CXR) using the modified Brixia (MBrixa) scoring system. The insertion (I)/deletion (D) polymorphism of the ACE gene and the serum levels of PTX3 were determined for all patients included in the study. RESULTS: This study included 80 patients. Using a cut-off serum level of PTX3 ≥ 2.765 ng/mL, the ROC analysis (AUC 0.871, 95% CI 0.787-0.954, p < 0.001) showed a sensitivity of 85.7% and specificity of 78.8% in predicting severe MBrixa scores. Compared to ACE I/I polymorphism, D/D polymorphism significantly increased the risk of severe CXR infiltrates, OR 7.7 (95% CI: 1.9-30.1), and p = 0.002. Significant independent predictors of severe CXR infiltrates include hypertension (OR 7.71), PTX3 (OR 1.20), and ACE D/D polymorphism (OR 18.72). Hypertension (OR 6.91), PTX3 (OR 1.47), and ACE I/I polymorphism (OR 0.09) are significant predictors of poor outcomes. CONCLUSION: PTX3 and ACE D/D polymorphism are significant predictors of the severity of COVID-19 pneumonia. PTX3 is a significant predictor of death.

Pentraxin 3 as a marker of development and severity of stable coronary artery disease.

PURPOSE: Inflammation plays a crucial role in the development of atherosclerotic plaques. Pentraxin 3 (PTX3) is produced at the site of inflammation and has been identified as a specific marker of atherosclerosis, vascular inflammation, and progression of the coronary artery disease (CAD). The aim of the study was to establish if PTX3 has potential relations with classical markers of cardiovascular risk, and if PTX3 may act as an independent risk factor of CAD occurrence and advancement. MATERIALS AND METHODS: The study included 98 patients with stable CAD confirmed in coronary angiography (CAD group) (median age 65 interquartile range [IQR] 61-72 years; 72 â€‹% men). The control group consisted of 40 patients without CAD. RESULTS: The CAD group had significantly higher PTX3 concentration compared to the control group. There was a correlation with age, male gender, lipid profile and intima-media thickness. There was no correlation between PTX3 concentration and the number of coronary vessels with significant atherosclerotic lesions and the advancement of atherosclerotic lesions on the Gensini scoring scale. The cut-off point was determined for 0.89 â€‹ng/ml for the exclusion of angiographically significant atherosclerotic lesions. CONCLUSIONS: Patients with CAD have significantly higher concentration of PTX3. There was no correlation between PTX3 and the advancement of angiographically significant atherosclerotic lesions in coronary arteries. Low PTX3 concentration may serve as an indicator for the absence of atherosclerosis.

Progress in the study of pentraxin-3(PTX-3) as a biomarker for sepsis.

Sepsis is a intricate pathological process characterized by life-threatening organ dysfunction resulting from a dysregulated host response to infection. It stands as a prominent cause of mortality among critically ill patients globally. The pivotal focus in sepsis management lies in the early identification and prompt administration of antimicrobial agents. Owing to the constraints of current diagnostic methodologies, marked by insufficient sensitivity and delayed outcomes, extensive research has been undertaken to ascertain novel biomarkers for sepsis. In this review, we provide an overview discussing the latest advancements in the study of PTX-3 as a biomarker for sepsis. We acknowledge pivotal discoveries from preceding research and engage in discourse regarding the challenges and limitations confronted by PTX-3 as a sepsis biomarker.

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.

Plasma pentraxin-3 levels and its role in childhood obesity-Is it anti-inflammatory? A matched group study.

OBJECTIVE: Obesity has been associated with chronic low-grade systemic inflammation. This study aimed to investigate the relationship of pentraxin-3 (PTX-3) with anthropometric measurements, dietary content and physical activity level in children. DESIGN: A matched group study. PATIENTS: This study was conducted with 91 children aged 6-17 years, divided into two groups: "non-obese group" (Body Mass Index Standard Deviation Score [BMI SDS] <95th percentile) and "obese group" (BMI SDS ≥95th percentile). MEASUREMENTS: Plasma PTX-3 levels. RESULTS: The mean age of 91 children included in the study was 12.34 ± 2.86 years. Plasma PTX-3 levels were significantly higher in obese children (p = .028). No significant correlation was found between BMI SDS and plasma PTX-3 values, but a weak positive correlation was found when physical activity level was controlled (r = .176, p = .049). In addition, it was found that fat mass was a partial mediator of plasma PTX-3 level, and an increase in the amount of subcutaneous adipose tissue negatively affected plasma PTX-3 level. Plasma PTX-3 level showed a weak positive correlation (r = .223, p = .017) with physical activity score and dietary polyunsaturated fatty acid intake, while a weak negative correlation with neutrophil-to-lymphocyte ratio. One unit increase in physical activity score or polyunsaturated fatty acid level caused 0.730 and 2.061 unit increases in plasma PTX-3 level, respectively; while one unit increase in dietary fat intake caused 0.413-unit decrease. CONCLUSION: There was an indirect relationship between the amount of subcutaneous adipose tissue and PTX-3 level. The results of our study suggested that plasma PTX-3 was associated with lower levels of inflammation in children.

Association between blood Pentraxin-3 concentrations and rheumatic diseases: A systematic review and meta-analysis.

BACKGROUND: Among the Pentraxins, the long Pentraxin-3 (PTX-3) is associated with several processes, particularly in the earliest phases of the innate humoral response. Increased blood PTX-3 concentrations have been observed in a wide range of conditions, from infectious to cardiovascular disorders. Since its increase is more rapid than C-reactive protein (CRP), PTX-3 can be useful to detect and monitor early inflammation. To dissect its pathophysiological role in rheumatic diseases (RD), we conducted a systematic review and meta-analysis comparing blood PTX-3 concentrations in RD patients and healthy individuals and investigating possible associations with clinical, demographic, and study characteristics. METHODS: We performed a search of published evidence until April 2024 in PubMed, Web of Science and Scopus, which led to the selection of 60 relevant manuscripts from a total of 1072 records. RESULTS: Our synthesis revealed a statistically significant difference in PTX-3 concentrations between RD patients and controls (standard mean difference, SMD = 1.02, 95% CI 0.77-1.26, p < .001), that correlated with CRP concentrations. The effect size was associated with geographical region of study conduction, RD type, with a reduction of the observed heterogeneity in patients with low LDL-cholesterol and triglycerides concentrations. CONCLUSIONS: Our study has shown a significant increase in blood PTX-3 concentrations in RD patients, which was associated with specific patient characteristics. Nevertheless, additional studies are needed to better define the utility of measuring PTX-3 in the early phase of RD. Our study was conducted in compliance with the PRISMA 2020 statement (study protocol available at PROSPERO CRD42024516600).

EGF-like growth factors upregulate pentraxin 3 expression in human granulosa-lutein cells.

The epidermal growth factor (EGF)-like factors, comprising amphiregulin (AREG), betacellulin (BTC), and epiregulin (EREG), play a critical role in regulating the ovulatory process. Pentraxin 3 (PTX3), an essential ovulatory protein, is necessary for maintaining extracellular matrix (ECM) stability during cumulus expansion. The aim of this study was to investigate the impact of EGF-like factors, AREG, BTC, and EREG on the expression and production of PTX3 in human granulosa-lutein (hGL) cells and the molecular mechanisms involved. Our results demonstrated that AREG, BTC, and EREG could regulate follicular function by upregulating the expression and increasing the production of PTX3 in both primary (obtained from 20 consenting patients undergoing IVF treatment) and immortalized hGL cells. The upregulation of PTX3 expression was primarily facilitated by the activation of the extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling pathway, induced by these EGF-like factors. In addition, we found that the upregulation of PTX3 expression triggered by the EGF-like factors was completely reversed by either pretreatment with the epidermal growth factor receptor (EGFR) inhibitor, AG1478, or knockdown of EGFR, suggesting that EGFR is crucial for activating the ERK1/2 signaling pathway in hGL cells. Overall, our findings indicate that AREG, BTC, and EREG may modulate human cumulus expansion during the periovulatory stage through the upregulation of PTX3.

Pentraxin 3: A Main Driver of Inflammation and Immune System Dysfunction in the Tumor Microenvironment of Glioblastoma.

Brain tumors are a heterogeneous group of brain neoplasms that are highly prevalent in individuals of all ages worldwide. Within this pathological framework, the most prevalent and aggressive type of primary brain tumor is glioblastoma (GB), a subtype of glioma that falls within the IV-grade astrocytoma group. The death rate for patients with GB remains high, occurring within a few months after diagnosis, even with the gold-standard therapies now available, such as surgery, radiation, or a pharmaceutical approach with Temozolomide. For this reason, it is crucial to continue looking for cutting-edge therapeutic options to raise patients' survival chances. Pentraxin 3 (PTX3) is a multifunctional protein that has a variety of regulatory roles in inflammatory processes related to extracellular matrix (ECM). An increase in PTX3 blood levels is considered a trustworthy factor associated with the beginning of inflammation. Moreover, scientific evidence suggested that PTX3 is a sensitive and earlier inflammation-related marker compared to the short pentraxin C-reactive protein (CRP). In several tumoral subtypes, via regulating complement-dependent and macrophage-associated tumor-promoting inflammation, it has been demonstrated that PTX3 may function as a promoter of cancer metastasis, invasion, and stemness. Our review aims to deeply evaluate the function of PTX3 in the pathological context of GB, considering its pivotal biological activities and its possible role as a molecular target for future therapies.

Role of High-sensitivity C-reactive Protein in Future Cardiovascular Events in Hemodialysis Patients.

BACKGROUND/AIM: The pathogenesis of cardio-vascular disease (CVD) in hemodialysis (HD) patients involves inflammation and oxidative stress. High-sensitivity C-reactive protein (hs-CRP) is an established inflammatory biomarker associated with CVD. Several studies have suggested that the inflammatory biomarker pentraxin-3 (PTX-3) and the oxidative stress-related biomarker soluble lectin-like low-density lipoprotein receptor-1 (sLOX-1) are novel biomarkers for CVD in non-HD populations. This study aimed to clarify the association of these established and novel biomarkers with future cardiovascular (CV) events in HD patients. PATIENTS AND METHODS: This was a single-center prospective cohort study that included 255 HD patients. The primary outcome was the composite of nonfatal and fatal CV events. The event-free survival rate between the two groups according to the median plasma level of each biomarker at baseline was evaluated using the Kaplan-Meier method. The risk for CV events at elevated levels of each biomarker was estimated using Cox proportional hazard model. RESULTS: We observed 44 CV events during the median follow-up period of 743 days. The event-free survival rate significantly differed between the two groups in hs-CRP but not in PTX-3 or sLOX-1. The unadjusted hazard ratio (HR) for CV events in patients with hs-CRP levels above the median was 2.63 [95% confidence interval (CI)=1.37-5.02]. The HR remained significant after adjusting for age, sex, history of CVD, and diabetes (HR=2.30; 95%CI=1.20-4.43). CONCLUSION: In HD patients, hs-CRP may have a predictable role for future CV events, whereas PTX-3 and sLOX-1 do not.

Pentraxin-3 and Outcomes in CKD: A Systematic Review and Meta-analysis.

Rationale & Objective: Long pentraxin-3 (PTX-3) serves as a biomarker for prognosticating adverse clinical outcomes in individuals with chronic kidney disease (CKD). The objective of the current meta-analysis was to evaluate the prognostic efficacy of PTX-3 in patients with CKD. In addition, we compared the prognostic effectiveness of PTX-3 and the short pentraxin C-reactive protein (CRP) in the identical cohort of patients with CKD. Study Design: A systematic review and meta-analysis. Setting & Participants: Patients with CKD treated with or without dialysis. Selection Criteria for Studies: A cohort study with a minimum 1-year follow-up. Data Extraction: Risk measurements, adjusted hazard risk with 95% CI, and modified variables. Analytical Approach: To aggregate the adjusted effect estimates, a fixed-effects or random-effects model was employed. Results: Nine studies covering 1,825 patients with CKD were selected in the present review. Six of the 9 studies exclusively included patients receiving hemodialysis. The collected findings indicated that patients with CKD in the highest tertile of PTX-3 demonstrated significantly higher risks of all-cause mortality (HR, 1.92; 95% CI, 1.44-2.56), cardiovascular death (HR, 1.98; 95% CI, 1.28-3.05), infectious death (HR, 5.26; 95% CI, 1.60-17.31), and fatal and nonfatal cardiovascular events (HR, 1.81; 95% CI, 1.35-2.42), as compared with those in the lowest tertile. These significant associations with risk were also observed when effect estimates were presented as per unit change in the PTX-3. Moreover, when comparing the prognostic value of PTX-3 and CRP in the same individuals (5 studies covering 904 patients), PTX-3 proved to be a satisfactory predictor of adverse events in these patients, whereas CRP failed to exhibit such predictive capability, regardless of the type of effect estimate used. Limitations: A relatively small sample size and some heterogeneity. Conclusions: Pentraxin 3 is associated with adverse events in individuals with CKD and may be a more reliable predictor of adverse clinical events than CRP in this population.

Systemic inflammatory markers are useful in predicting the prognosis of patients with CKD. Pentraxin-3 (PTX-3) is an emerging biomarker of inflammation compared with other members of the pentraxin family, such as C-reactive protein (CRP). This meta-analysis evaluated the prognostic value of PTX-3 in predicting adverse outcomes in patients with CKD. Also, we compared the prognostic values between PTX-3 and CRP in the subset of studies with data on CRP. We found that patients with CKD with higher circulating PTX-3 levels had a significantly heightened risk of adverse outcomes compared with those with lower PTX-3 levels. By contrast, CRP did not appear to be a good predictor of adverse events. Pentraxin-3 might be a more reliable prognostic marker than CRP in patients with CKD.

Neutrophil activation biomarker pentraxin 3 for diagnosis and monitoring of macrophage activation syndrome occurrence in adult-onset Still's disease.

Macrophage activation syndrome (MAS) is a potentially fatal consequence of adult-onset Still's disease (AOSD), driven by a cytokine storm. Efficient early diagnosis of AOSD-associated MAS requires a sensitive and specific biomarker. In this study, we demonstrated that pentraxin 3 (PTX3), an acute phase protein, was associated with AOSD disease activity and served as a biomarker for AOSD-MAS. PTX3 levels were significantly increased in AOSD patients compared to other autoimmune diseases and healthy controls. Plasma PTX3 levels showed positive correlations with inflammatory markers, the systemic score and the HScore. In active AOSD with MAS, PTX3 levels were higher compared to those in non-AOSD haemophagocytic lymphohistiocytosis (HLH) patients. Moreover, the PTX3's area under the curve value for distinguishing AOSD with MAS exceeded that of soluble interleukin-2 receptor, ferritin and C-reactive protein. Furthermore, plasma levels of PTX3 were associated with circulating NET-DNA levels. To fully understand the underlying mechanism of PTX3 prompting AOSD and AOSD-MAS progression, we discovered that neutrophils exhibited enhanced NET formation and mitogen-activated protein kinases (MAPK) pathway activation upon PTX3 stimulation. More importantly, PTX3-induced NET formation was effectively dampened by MAPK pathway inhibitors. These findings collectively revealed that PTX3 has a favorable correlation with disease activity and may serve as a potential biomarker to differentiate AOSD patients with MAS. Additionally, PTX3 induces NET release via the MAPK pathway, suggesting a pathogenic role in AOSD-MAS.

Protopanaxadiol improves lupus nephritis by regulating the PTX3/MAPK/ERK1/2 pathway.

Lupus nephritis (LN) is a kidney disease that occurs after systemic lupus erythematosus (SLE) affects the kidneys. Pentraxin 3 (PTX3) is highly expressed in the serum of patients with LN. Renal PTX3 deposition is directly related to clinical symptoms such as proteinuria and inflammation. The excessive proliferation of mesangial cells (MCs) is one of the representative pathological changes in the progression of LN, which is closely related to its pathogenesis. Protopanaxadiol (PPD) is the main component of ginsenoside metabolism and has not been reported in LN. The aim of this study was to investigate the relationship between PTX3 and mesangial cell proliferation and to evaluate the potential role and mechanism of PPD in improving LN. PTX3 is highly expressed in the kidneys of LN patients and LN mice and is positively correlated with renal pathological indicators, including proteinuria and PCNA. The excessive expression of PTX3 facilitated the proliferation of MCs, facilitated the activation of the MAPK/ERK1/2 signaling pathway, and increased the expression of HIF-1α. Further studies showed that PPD can effectively inhibit the abnormal proliferation of MCs with high expression of PTX3 and significantly improve LN symptoms such as proteinuria in MRL/lpr mice. The mechanism may be related to the inhibition of the PTX3/MAPK/ERK1/2 pathway. In this study, both in vitro, in vivo, and clinical sample results show that PTX3 is involved in the regulation of MCs proliferation and the early occurrence of LN. Natural active compound PPD can improve LN by regulating the PTX3/MAPK/ERK1/2 pathway.