PTX3 Levels Research Articles

The role of pentraxin 3 and cathepsin B levels in pregnancies complicated by preeclampsia

Objective The objective of this study was to compare the levels of cathepsin B and pentraxin 3 in maternal serum of pregnant women with preeclampsia in the second trimester, to ascertain the impact of these levels on maternal and fetal outcomes, and to present a comprehensive analysis of the combined effects of cathepsin B and pentraxin 3 levels. Methods This prospective case-control study was conducted at Bursa Yuksek Ihtisas Training and Research Hospital between 1 January 2022 and 31 December 2022. The study included 78 pregnant women diagnosed with preeclampsia and 78 healthy pregnant women in the second trimester, between the ages of 18 and 45. Once a diagnosis of preeclampsia was established, maternal serum samples were obtained from the pregnant women prior to the initiation of any therapeutic intervention. Once all samples had been collected, the values for cathepsin B and pentraxin 3 were determined using the ELISA method. Results The results demonstrated a statistically significant elevation in the levels of pentraxin 3 (p = 0.008) and cathepsin B (p = 0.005) in pregnancies affected by preeclampsia when compared to those deemed healthy. Moreover, pentraxin-3 (p = 0.007) and cathepsin B (p = 0.002) were found to be significantly elevated in severe preeclampsia compared to mild preeclampsia. A comparison of the groups with and without HELLP syndrome revealed no statistically significant difference between the two groups. The ROC analysis revealed that the Cathepsin B 7.04 cut-off value was statistically significantly associated with the prediction of preeclampsia in all cases, with a sensitivity of 78.2% and a specificity of 47.4% (p = 0.005, AUC = 0.631). Conclusion The levels of CB and PTX3 may be employed as biomarkers to facilitate the early diagnosis of PE during the second trimester. Furthermore, these biomarkers may prove to be promising for the prediction of PE severity.

Serum pentraxin-3 expression varies according to polycystic ovary syndrome phenotypes.

Pentraxin-3 (PTX-3) is a multibiological protein involved in cumulus cell expansion, fertilization, and implantation. This study was designed to analyze how circulating PTX-3 levels change in women with polycystic ovary syndrome (PCOS). A total of 50 Turkish participants, 35 of whom had PCOS and 15 of whom were fertile, were included in the study. Patients in the PCOS group were divided into 4 different phenotypes according to the NIH criteria (phenotypes A-D). The number of patients in phenotype A was the highest 13 (37.1%). In the calculations made without phenotyping, the serum ptx3 levels of the PCOS group were found to be significantly lower compared to the fertile control group (3.32 ± 0.73 ng/mL vs 4.97 ± 1.29 ng/mL; P < .001). The ptx3 value of phenotypes A and B was significantly lower than phenotype D (P = .008 and P = .009, respectively). When the phenotypes were compared with the fertile control group, the PTX-3 levels of phenotypes A and B were significantly lower than the fertile group. Although the ptx3 levels of phenotypes C and D were lower than the fertile group, the difference did not reach statistical significance. This is the first study to investigate serum ptx3 levels by phenotype in PCOS. While serum PTX-3 levels decreased in phenotypes A and B, ptx3 levels in phenotypes C and D were similar in fertile patients.

Profiles of cytokines in patients with antineutrophil cytoplasmic antibody-associated vasculitis.

This study aimed to identify plasma biomarkers that are significantly altered in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and are closely associated with AAV disease activity, as well as to explore their role in the pathogenesis of AAV. Cytokines were measured using Human Immune Response Panel 80-Plex in plasma from 59 patients with AAV and 20 healthy controls (HCs). The differentially expressed cytokines between the two groups and the possible signaling pathway involved in the pathogenesis of AAV were analyzed by bioinformatics. Relationship analysis was performed between these cytokines and clinical parameters to identify the biomarkers that can effectively indicate disease activity. We identified 65 differentially expressed cytokines between the two groups. Among them, 43 cytokines significantly affected the risk of AAV. Bioinformatic analysis showed that the 43 cytokines were primarily enriched in signaling pathways such as cytokine-cytokine receptor interaction, viral protein interaction with cytokine and cytokine receptor, chemokine signaling pathway, and IL-17 signaling pathway. The levels of 25 cytokines were significantly positively correlated with Birmingham Vasculitis Activity Score (BVAS), and the levels of 2 cytokines were significantly negatively correlated with BVAS. Receiver operating characteristic analysis showed that 9 cytokines can distinguish between disease relapse and remission (PTX3: area under curve (AUC)=0.932, IL34: AUC=0.856, IL2RA: AUC=0.833, CCL23: AUC=0.826, VEGFA: AUC=0.811, TNFSF13: AUC=0.795, Granzyme A: AUC=0.788, CSF3: AUC=0.773 and IL1A: AUC=0.765). The elevated levels of these 9 cytokines suggested a risk of disease relapse. The AUC of CCL11 in disease relapse and remission was 0.811 (p=0.0116). Unlike the other 9 cytokines, a negatively association existed between CCL11 level and the risk of disease relapse. A group of cytokines that may be involved in AAV pathogenesis was identified. Increased PTX3, IL34, IL2RA, CCL23, and VEGFA levels correlate with active disease in AAV and may be used as biomarkers to identify the disease relapse of AAV.

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.

SMR and PTX3 levels associate with COVID-19 outcome and survival but not with Long COVID

Biomarkers for monitoring COVID-19 disease course are lacking. Study aim was to identify biomarkers associated with disease severity, survival, long-term outcome, and Long COVID. As excessive macrophages activation is a hallmark of COVID-19 and complement activation is key in this, we selected the following proteins involved in these processes: PTX3, C1q, C1-INH, C1s/C1-INH, and sMR. EDTA-plasma concentrations were measured in 215 patients and 47 controls using ELISA. PTX3, sMR, C1-INH, and C1s/C1-INH levels were associated with disease severity. PTX3 and sMR were also associated with survival and long-term immune recovery. Lastly, sMR levels associate with ICU admittance. sMR (AUC 0.85) and PTX3 (AUC 0.78) are good markers for disease severity, especially when used in combination (AUC 0.88). No association between biomarker levels and Long COVID was observed. sMR has not previously been associated with COVID-19 disease severity, ICU admittance or survival and may serve as marker for disease course.

#887 Complement biomarkers in IgA nephropathy and IgA vasculitis with renal involvement: can urine rather than blood be the answer?

Abstract Background and Aims IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide. Dysregulation of the complement system is considered a part of the pathogenesis and can occur both in the circulation and locally in the kidney. Despite this, most studies have focused on complement biomarkers in the blood, rather than in urine. Our aim was to evaluate a wide range of complement-related proteins in blood and urine at diagnosis and their association with disease activity in biopsy findings, proteinuria, and outcome. We added PTX-3, a protein expressed in activated endothelial cells, which can be both produced by and activate mesangial cells in IgAN and has a function in all three complement pathways. Adult-onset IgA vasculitis with renal involvement (IgAVN) shares many similarities with IgAN and cannot currently be distinguished by kidney biopsy or any established biomarker. We therefore also aimed to compare the same biomarkers between these two disorders. Method In a Swedish cohort of 96 patients with IgAN (n = 65) and IgAVN (n = 31), who had been followed prospectively for a median of 10.8 years, we performed the following analysis in plasma and urine in samples stored at the time of kidney biopsy. Analyses in plasma (p-) included C3bc, C4c, C5b-9, MASP2, MASP3, MAP1, FCN 1-3, MBL, CL11 and PTX-3 and in urine (u-) C3bc, C4c, C5b-9, MASP3, FCN2, FCN3, MBL and PTX-3. An in-house developed sandwich ELISA was used for all analyses. Kidney biopsies were classified according to the Oxford MEST-C score, describing (simplified for this small cohort) the presence vs absence (1 vs 0) of mesangial proliferation (M), endocapillary proliferation (E), segmental sclerosis (S), tubular atrophy/interstitial fibrosis (T) and crescents (C). Severe outcome was defined by a combination of an eGFR slope &amp;gt; 2.5 ml/min/1.73 m2 per year or end stage kidney disease. For statistical analysis, Mann-Whitney U test was performed for comparison between independent groups, Chi squared test and Fisher's test for categorical variables and Spearman's ranks test for correlation analysis. Median values are presented without IQR for this abstract. Results Urine samples were available in 59 patients (IgAN n = 39, IgAVN n = 20). Patients with detectable u-MBL (28.9%) and u-C5b-9 (27.1%) had higher levels of proteinuria than those with undetectable levels (1.5 g/d vs 0.71g/d; p = 0.009 and 2.3 g/d vs 0.7 g/d respectively; p &amp;lt; 0.001). Lower eGFR (71 ml/min/1.73 m2 vs 88 ml/min/1.73 m2; p = 0.034) were observed if u-C5b-9 was measurable. Detectable levels of u-PTX-3 and u-MBL were more often found in the presence of M1 vs M0 (53% vs 20%; p = 0.022 and 47% vs 12.5%; p = 0.011), E1 vs E0 (55% vs 14%; p = 0.001 and 40% vs 11%; p = 0.020) and C1 vs C0 (56% vs 11%; p = 0.003 and 44% vs 11%; p = 0.012). No differences in proteinuria or eGFR were seen in patients with or without detectable u-PTX-3. The degree of proteinuria was positively correlated to the levels of u-C3bc (r = 0.33; p = 0.011) and u-C4c (r = 0.39; p &amp;lt; 0.001). U-C4c levels were higher in patients with M1 vs M0 (54.4 Au/mL vs 23.8 Au/mL; p = 0.037) and T1 vs T0 (53.2 Au/mL vs 23.8 Au/mL; p = 0.034). Concerning the analyses in plasma (n = 95), lower p-MASP3 and p-CL11 levels were correlated with lower eGFR (r = 0.29; p = 0.004 and r = 0.31, p = 0.002). Moreover, lower p-MASP3 levels were detected in patients with E1 vs E0 (2918 ng/mL vs 3404 ng/mL; p = 0.002) and C1 vs C0 (3053 ng/mL vs 3427 ng/mL; p = 0.015). Both p-C5b-9 (13.3 Au/mL vs 8.2 Au/mL; p = 0.001) and p-FCN 1 (395 ng/mL vs 289 ng/mL; p = 0.001) were higher in patients with C1 vs C0. No single complement-related protein was associated with severe outcome, and no statistically significant differences in plasma or urine levels between patients with IgAN and IgAVN were observed. Conclusion Increased urinary levels of MBL and PTX-3 could be potential biomarkers of disease activity in both IgAN and IgAVN, whereas excretion of C5b-9 might be more unspecific and associated with chronic damage. However, these results need to be confirmed in larger and more ethnically diverse cohorts. The impact of treatment on these potential biomarkers for disease activity need to be evaluated in longitudinal studies.

Inhibition of Amyloid-β (Aβ)-Induced Cognitive Impairment and Neuroinflammation in CHI3L1 Knockout Mice through Downregulation of ERK-PTX3 Pathway.

Several clinical studies reported that the elevated expression of Chitinase-3-like 1 (CHI3L1) was observed in patients suffering from a wide range of diseases: cancer, metabolic, and neurological diseases. However, the role of CHI3L1 in AD is still unclear. Our previous study demonstrated that 2-({3-[2-(1-Cyclohexen-1-yl)ethyl]-6,7-dimethoxy-4-oxo-3,4-dihydro-2-quinazolinyl}culfanyl)-N-(4-ethylphenyl)butanamide, a CHI3L1 inhibiting compound, alleviates memory and cognitive impairment and inhibits neuroinflammation in AD mouse models. In this study, we studied the detailed correlation of CHI3L1 and AD using serum from AD patients and using CHI3L1 knockout (KO) mice with Aβ infusion (300 pmol/day, 14 days). Serum levels of CHI3L1 were significantly elevated in patients with AD compared to normal subjects, and receiver operating characteristic (ROC) analysis data based on serum analysis suggested that CHI3L1 could be a significant diagnostic reference for AD. To reveal the role of CHI3L1 in AD, we investigated the CHI3L1 deficiency effect on memory impairment in Aβ-infused mice and microglial BV-2 cells. In CHI3L1 KO mice, Aβ infusion resulted in lower levels of memory dysfunction and neuroinflammation compared to that of WT mice. CHI3L1 deficiency selectively inhibited phosphorylation of ERK and IκB as well as inhibition of neuroinflammation-related factors in vivo and in vitro. On the other hand, treatment with recombinant CHI3L1 increased neuroinflammation-related factors and promoted phosphorylation of IκB except for ERK in vitro. Web-based gene network analysis and our results showed that CHI3L1 is closely correlated with PTX3. Moreover, in AD patients, we found that serum levels of PTX3 were correlated with serum levels of CHI3L1 by Spearman correlation analysis. These results suggest that CHI3L1 deficiency could inhibit AD development by blocking the ERK-dependent PTX3 pathway.

Comparison of Pentraxin-3 in Migraine Patients without Aura and Healthy Controls

Background and Objectives: Migraine is a common cerebrovascular condition marked by one-sided, pulsating headache, which may or may not be accompanied with an aura. Migraine is mostly found in females who are of childbearing age. One of the speculated mechanisms for the pathophysiology of migraine is endothelial dysfunction. A new biomarker of inflammatory disorders, pentraxin-3 is often produced by endothelium injury. In earlier investigations, it was shown that migraine sufferers had elevated levels of pentraxin-3. Our study's objectives were to analyze the serum pentraxin-3 levels in migraine sufferers without aura and healthy controls.Methods: It was a cross-sectional comparative study. This was done at the IMBB Department, University of Lahore, Lahore Pakistan, from March 2020 to April 2022. We took 40 diagnosed migraine cases and 40 healthy controls. Detailed examination was done and proformas were filled by both cases and controls. Serum was collected by each of them and pentraxin-3 values were determined by using specific Elisa kits. SPSS version 22 was used for statistical analysis. For normality of data Shapiro wilk test was used. Mann whiteny U test was used for the comparision of means of pentraxin-3 in migrainers and healthy controls.Results: The data were non-normally distributed after the Shapiro-Wilk Test. The average age of the controls was 25±6.06 years, while that of individuals with migraines was 26±7.78 years. Patients with migraine were mostly women. The majority of the patients had BMI category 18 to 24.5. Patients with migraine had mean pentraxin-3 levels of 145.75 ±157.7 pg/l, compared to 43.65 ±33.01 pg/l in the control group. Median was100.5 in cases and 31.15 in controls. P-value was 0.0001.Conclusion: When compared to the control group, migraine patients had considerably higher blood levels of PTX-3, and no correlations between age, BMI, marital status, smoking history, and usage of preventative medications were found.Key words: migraine, pentraxin-3, endothelial dysfunction, C-reactive protein (CRP),

The correlation between pentraxin-3, matrix metalloproteinase-9, and estimated glomerular filtration rate in patients with chronic kidney disease

Background: Chronic kidney disease (CKD) is diagnosed when there is a sustained decrease in the estimated glomerular filtration rate (EGFR) over a period of more than 3 months. While Pentraxin-3 (PTX-3) and Matrix Metalloproteinase-9 (MMP-9) levels increase during the acute phase of the kidney injury, chronic conditions often exhibit alteration in the epithelial mesenchymal transition (EMT).Objectives: This study aimed to elucidate the correlation between serum PTX-3, MMP-9, and eGFR in patients with CKD. Method: Thirty hypertensive patients with CKD stages 3, 4, and 5, aged between 16 and 65 years, were enrolled in the study (15 males and 15 females). Diagnosis of CKD was based on the 2012 Kidney Disease Improving Global Outcomes (KDIGO) criteria, utilizing serum creatinine, and CKD-epidemiology Collaboration (CKD-EPI) estimates. Subsequently, serum MMP-9 and PTX-3 levels were quantified. Result: Patients with CKD exhibited significantly higher serum levels of PTX3 and MMP9. Furthermore. a significant negative connection between PTX-3, MMP-9, and EGFR was observed. Additionally, CKD patients displayed a correlation between PTX-3 and MMP-9 concentrations.Conclusion: Plasma levels of PTX-3 and MMP-9 serve as unique, promising, and important markers that contribute to the pathogenesis of CKD.

Improved therapeutic consistency and efficacy of CD317+ MSCs through stabilizing TSG6 by PTX3

BackgroundPreviously, we have demonstrated that the batch variations of human platelet lysate (conventional MSC expansion medium) induce MSC heterogeneity and therapeutic inconsistency. On the other hand, the MSCs expanded with chemical defined medium have improved therapeutic consistency.MethodsIn the current study, we studied the MSC subpopulation composition and variation in different types and batches of MSC expansion medium with scRNA-seq analysis.ResultsMSCs expanded with different batches of media have higher levels of heterogeneity from the perspective of cell subpopulation composition at transcriptome levels and therapeutic inconsistency. The CD317+ subpopulation has enhanced immune suppression activities. And the percentage of CD317+ MSCs within MSCs is tightly correlated with its immune suppression activities, and also contributes to the heterogeneity and therapeutic inconsistency of MSCs. the CD317+ MSCs have increased expression levels of PTX3, which might stabilize the TSG6 protein and improve the therapeutic effectsConclusionsThus, purifying CD317+ MSCs is one efficient strategy to reduce MSC heterogeneity and increase the therapeutic consistency of MSCs.

Prognostic value of serum IGF-1, Gal-3, and PTX-3 levels in elderly patients with chronic heart failure.

To evaluate the diagnostic and prognostic value of insulin-like growth factor-1 (IGF-1), galactoagglutinin-3 (GAL-3), and pentamerin-3 (PTX-3) levels in elderly patients with chronic heart failure (CHF). In this retrospective study, 107 elderly CHF patients treated in Xiangyang Central Hospital were designated as the observation group, and 60 healthy individuals were selected as the control group. The cardiac function indexes and serum IGF-1, Gal-3, and PTX-3 levels were compared between the two groups. Furthermore, the serum IGF-1, Gal-3, and PTX-3 levels in patients across different cardiac function grades were compared, as well as in patients with poor or favorable prognosis. Additionally, receiver operating characteristic (ROC) curve was adopted to explore the diagnostic value of serum IGF-1, Gal-3, and PTX-3 levels for senile CHF; and multivariate logistic regression analysis was used to screen the independent factors affecting patients' prognosis. The serum IGF-1 level was significantly lower, while the levels of Gal-3 and PTX-3 were significantly higher in the observation group than those of the control group (all P<0.05). The serum IGF-1 level in patients with cardiac function grade IV was lower than that of the patients with cardiac function grade II and III, while the levels of Gal-3 and PTX-3 were higher than those with cardiac function grade II and III (all P<0.05). The serum IGF-1 level in the patients with cardiac function grade III was lower than those with cardiac function grade II, while the levels of Gal-3 and PTX-3 were higher in patients with grade III than those with grade II (all P<0.05). The serum IGF-1 level was lower, while the levels of Gal-3 and PTX-3 were higher in the patients with poor prognosis than those with favorable prognosis (all P<0.05). In elderly CHF patients, IGF-1 level were decreases, while the levels of Gal-3 and PTX-3 were increase. These biomarkers show high sensitivity in diagnosing CHF and are closely linked to the prognosis, indicating their value for clinical assessment and management of CHF.

Differential blood-based biomarkers of subcortical and deep brain small vessel disease.

Cerebral small vessel disease is the most common cause of lacunar strokes (LS). Understanding LS pathogenesis is vital for predicting disease severity, prognosis, and developing therapies. To research molecular profiles that differentiate LS in deep brain structures from those in subcortical white matter. Prospective case-control study involving 120 patients with imaging-confirmed LS and a 120 control group. We examined the relationship between Alzheimer's disease biomarkers [amyloid beta (Aβ1-40, Aβ1-42)], serum inflammatory marker (interleukin-6, IL-6), and endothelial dysfunction markers [soluble tumor necrosis factor-like weak inducer of apoptosis, and pentraxin-3 (sTWEAK, PTX3)] with respect to LS occurring in deep brain structures and subcortical white matter. In addition, we investigated links between LS, leukoaraiosis presence (white matter hyperintensities, WMHs), and functional outcomes at 3 months. Poor outcome was defined as a modified Rankin scale >2 at 3 months. Significant differences were observed in levels of IL-6, PTX3, and sTWEAK between patients with deep lacunar infarcts and those with recent small subcortical infarcts (20.8 versus 15.6 pg/mL, p < 0.001; 7221.3 versus 4624.4 pg/mL, p < 0.0001; 2528.5 versus 1660.5 pg/mL, p = 0.001). Patients with poor outcomes at 3 months displayed notably higher concentrations of these biomarkers compared to those with good outcomes. By contrast, Aβ1-40 and Aβ1-42 were significantly lower in patients with deep LS (p < 0.0001). Aβ1-42 levels were significantly higher in patients with LS in subcortical white matter who had poor outcomes. WMH severity only showed a significant association with deep LS and correlated with sTWEAK (p < 0.0001). The pathophysiological mechanisms of lacunar infarcts in deep brain structures seem different from those in the subcortical white matter. As a result, specific therapeutic and preventive strategies should be explored.

Association of PTX3 gene polymorphisms and PTX3 plasma levels with leprosy susceptibility

BackgroundPentraxin 3 (PTX3) is a soluble pattern recognition receptor that plays a crucial role in modulating the inflammatory response and activating the complement system. Additionally, plasma PTX3 has emerged as a potential biomarker for various infectious diseases. The aim of this study was to evaluate the association of PTX3 gene polymorphisms and PTX3 plasma levels with susceptibility to leprosy and clinical characteristics.MethodsPatients with leprosy from a hyperendemic area in the Northeast Region of Brazil were included. Healthy household contacts and healthy blood donors from the same geographical area were recruited as a control group. The rs1840680 and rs2305619 polymorphisms of PTX3 were determined by real-time PCR. Plasma levels of PTX3 were determined by ELISA.ResultsA total of 512 individuals were included. Of these, 273 were patients diagnosed with leprosy; 53 were household contacts, and 186 were healthy blood donors. No association was observed between PTX3 polymorphisms and susceptibility to leprosy or development of leprosy reaction or physical disability. On the other hand, plasma levels of PTX3 were significantly higher in patients with leprosy when compared to household contacts (p = 0.003) or blood donors (p = 0.04). It was also observed that PTX3 levels drop significantly after multidrug therapy (p < 0.0001).ConclusionsOur results suggest that PTX3 may play an important role in the pathogenesis of leprosy and point to the potential use of this molecule as an infection marker.

Nonlinear associations between computed tomography-measures of adiposity and long pentraxin-3 in the Multi-Ethnic Study of Atherosclerosis.

Long pentraxin-3 (PTX-3) is an acute phase protein associated with cardiovascular disease, lung injury, and mortality. We evaluated the association between computed tomography (CT)-measurements of adipose tissue and plasma levels of PTX-3. We performed a cross-sectional analysis of community-dwelling adults enrolled in the multi-center Multiethnic Study of Atherosclerosis who underwent cardiac or abdominal CT and had available PTX-3 measurements. There was a U-shaped association between pericardial adipose tissue volume (PAT), abdominal visceral adipose tissue area (VAT), hepatic attenuation, and PTX-3 levels, with extremes of adiposity associated with greater PTX-3 levels. Using multivariable-adjusted piecewise regression models, among participants with low PAT, every 1% increase in PAT volume was associated with a 13.8% decrease in PTX-3 (95% confidence interval [CI] -21.6 to -6.0); among participants with high PAT, every 1% increase in PAT volume was associated with a 6.0% increase in PTX-3 (95% CI -0.4 to 12.5). Results were similar for abdominal VAT and hepatic attenuation. In a cohort of community-dwelling adults, we demonstrated a "U-shaped" association between pericardial, abdominal visceral, and hepatic adiposity with PTX3 levels, suggesting that extreme adiposity is associated with greater circulating levels of PTX3. Further work is required to identify the mechanisms linking adiposity and PTX-3.

Bone morphogenetic protein 6 induces downregulation of pentraxin 3 expression in human granulosa lutein cells in women with polycystic ovary syndrome

PurposeTo evaluate whether PTX3 is differentially expressed in the granulosa lutein cells derived from women with PCOS and whether BMP6 can regulate the expression of PTX3 in hGL cells.MethodsThe expression levels of BMP6 and PTX3 in granulosa lutein cells were evaluated by RT-qPCR. The correlation between the expression levels of BMP6 /PTX3 and oocyte quality indexes were analyzed using clinical samples. The cells were incubated with BMP6 at different concentrations and times to check the expression of PTX3 in KGN cells. TGF-β type I inhibitors and small interfering RNA targeting ALK2/3/6,SMAD1/5/8 and SMAD4 were used to study the involvement of SMAD dependent pathways in KGN cells.ResultsThe levels of BMP6 in hGL cells were negatively correlated with the corresponding oocyte maturation rate and high-quality embryo rate, whereas the levels of PTX3 were positively correlated with the corresponding oocyte maturation rate in PCOS. Additionally, the in vitro cell cultured results showed BMP6 significantly inhibited the expression of PTX3 in KGN cells. Furthermore, using a dual inhibition approach (kinase inhibitors and small interfering RNAs), we identified the ALK2/ALK3 type I receptors and BMPR2/ACVR2A type II receptors and the downstream SMAD1/SMAD5-SMAD4 signaling pathway were responsible for the BMP6-induced cellular activities in KGN cells.ConclusionsThe suppressive effect of BMP6 on PTX3 was mediated by ALK2/ALK3 type I receptors and BMPR2/ACVR2A type II receptors in granulosa cells through the SMAD1/5-SMAD4 dependent signaling pathway in PCOS.Our findings provides new insights into the understanding of the pathogenesis of PCOS-related ovulatory disorders.

Study of Pentraxin-3 as an Early Marker of Diabetic Vascular Complications in Children and Adolescents with Type 1 Diabetes Mellitus

Background Vascular complications are the major cause of morbidity and mortality in diabetic patients. These can result from interactions between systemic metabolic abnormalities, such as hyperglycemia, dyslipidemia, genetic and epigenetic modulators, and local tissue responses to toxic metabolites. Aim of the Work To assess the role of PTX3 as an early marker of vascular complications in children and adolescents with type 1 diabetes mellitus and its correlation with metabolic control and its relation to hsCRP level. Patients and Methods Fifty adolescents with type 1 diabetes mellitus and 40 age and sex matched control group, Detailed history taking, full systemic examination were done, Patients also were investigated using HbA1c, lipid profile, ALT, Alb/Cr ratio in urine, PTX3, hsCRP and carotid intima media thickness (CIMT). An informed consent was obtained from patients, controls or their legal guardians before enrollment in the study. Inclusion criteria Patients with type 1 diabetes their age ranging from 5 to 18 years old with at least 5 years disease duration and on regular clinic visits and multiple daily insulin therapy . Exclusion criteria Patients with proven vascular complications and those with any clinical evidence of infection, hematological diseases, tumors, liver dysfunction, urinary tract disorders, connective tissue disease, or other autoimmune diseases, also patients with morbid obesity were excluded. Results PTX3 and hsCRP were significantly higher in patients compared to control group. A significant positive correlation between serum PTX3 and level of HbA1c%, level of Triglycerides (TG), level of Total Cholesterol was observed. Additionally, PTX3 and hsCRP levels were elevated in patients with elevated lipid profile (TG and Cholesterol) and high HbA1c% level in comparison with those with normal lipid profile and those with controlled HbA1c% level (p &amp;lt; 0.001). No significant difference was found between patients and control groups as regard CIMT. Conclusion . The increased levels of PTX3 and hsCRP in patients with uncontrolled diabetes even before development of both microvascular and macrovascular complications add a promising tool for their follow up and applying early protective measures.

The Effect of Interval Training on PTX3, VCAM-1, and CRP in Rats with Metabolic Syndrome

Background: Sedentary lifestyle and lack of exercise cause cardiovascular diseases and metabolic syndrome. Decreased movement in recent decades has caused cardiovascular diseases. Methods: In this research, 35 male Wistar rats weighing 220 ± 20 g were divided into 5 groups (seven rats in each group) by a simple random method. The first and second experimental groups were given 100 grams per liter of fructose with water for 6 weeks, and the third experimental group received this for 14 weeks. The training group performed the interval training protocol on the treadmill for eight weeks and 5 days a week. One-way analysis of variance (ANOVA) was used to compare the groups. Results: The use of the fructose diet for 6 weeks and 14 weeks caused metabolic syndrome in male Wistar rats. Induction of metabolic syndrome increased the plasma levels of PTX3, VACM-1, and CRP at the end of 6 weeks (P = 0.001, P = 0.018, and P = 0.004, respectively) and the fourteenth week (P = 0.001, P = 0.001, and P = 0.001, respectively). Eight weeks of interval training significantly reduced PTX3, VACM-1, and CRP (P = 0.034, P = 0.027 and P = 0.021, respectively). Conclusions: The fructose diet caused metabolic syndrome and a significant increase in inflammatory markers in rats, and high-intensity interval training significantly reduced inflammatory factors in them.

Diagnostic Value of PTX-3 Combined with PCT and CRP for Neonatal Sepsis

Aim: Neonatal sepsis is a critical illness among neonates and is the leading cause of neonatal death. In this study, we compared the changes in serum PTX-3 levels in neonates with sepsis and non-septicemia, as well as the diagnostic advantages and value of serum PTX-3 compared to traditional indicators such as WBC, CRP, and PCT. Methods: A total of 109 neonates were included in this study. Neonates were divided into three groups: 35 neonates were assigned to the sepsis group; 36 to the local infection group; and 38 assigned to the control group. Blood was collected to measure complete blood counts, CRP, PCT, liver and kidney function, lactate, and PTX-3 levels. Results: CRP, PCT, and PTX-3 in the sepsis group were significantly higher compared to the local infection group and non-infection group (P&lt;0.01 or P&gt;0.05). PCT and PTX-3 levels in the local infection group were significantly higher compared to the non-infection group (P&gt;0.05). The combination of WBC+CRP+PCT+PTX-3 was more sensitive for the diagnosis of neonatal infection. For the diagnosis of neonatal sepsis, CRP was the most sensitive index, with PTX-3 having the best specificity. The combination of WBC+CRP+PTX-3 was found to significantly improve the sensitivity and specificity of diagnosis. Conclusion: PTX-3 could be used as a new biomarker for neonatal sepsis, while the combination with WBC, CRP, and PCT could significantly improve the sensitivity and specificity for sepsis diagnosis.

Alpha-Fetoprotein as a Factor of Differentiation and Functional Activity of Myeloid-Derived Suppressor Cells.

We studied the role of alpha-fetoprotein (AFP) in regulation of differentiation and functional activity of human myeloid-derived suppressor cells (MDSC) in vitro. To obtain MDSC, CD11b+ cells were isolated from the peripheral blood of healthy donors followed by cytokine induction (IL-1β+GM-CSF) into the MDSC phenotype. The cell functions were assessed by the expression of indoleamine 2,3-dioxygenase (IDO) and arginase-1 (Arg1) and cytokine profile of the cell cultures. Native AFP did not affect the total number of MDSC and the percentage of polymorphonuclear MDSC (PMN-MDSC), but increased the number of monocytic MDSC (M-MDSC). AFP did not change the expression of Arg1, but in low concentrations (10 and 50 U/ml) increased the number of IDO-containing cells. AFP modulated the cytokine profile of CD11b+ cells: it reliably decreased the level of IL-19 (50 and100 U/ml) and showed a tendency to decrease the levels of IL-34, MMP-2, sCD163, CHI3L1, OPN and to increase the levels of IL-29, IL-32, APRIL, PTX3, and sTNF-R1. Thus, we have demonstrated a regulatory effect of native AFP at the level of MDSC generated from CD11b+ cells under conditions of cytokine induction in vitro.

Effects of insulin-like growth factor 1, leukemia inhibitory factor, and basic fibroblast growth factor on goat oocyte maturation and early embryonic development in vitro

In this study, we investigated the effects of insulin-like growth factor 1 (IGF-1), leukemia inhibitory factor (LIF), and basic fibroblast growth factor (bFGF) on the in vitro maturation of goat oocytes and early embryonic development of in vitro-fertilized (IVF) oocytes. We also aimed to prepare an efficient in vitro maturation culture system for goat oocytes as a technical basis for improving both the quality of goat oocytes and the efficiency of embryo production in vitro. The experimental results revealed that the addition of bFGF (40 ng/mL), LIF (20 ng/mL), and IGF-1 (20 ng/mL) to the maturation medium improved the maturation rate of goat oocytes. Compared with the control group, the in vitro maturation rate of oocytes (83.0% vs. 70.93%, P < 0.05) and the development rate of IVF blastocysts (45.88% vs. 35.81%, P < 0.05) in the bFGF, LIF, and IGF-1 (FLI) group were significantly increased. The total number of developing blastocysts (114.40 vs. 83.20, P < 0.05) and the ratio of inner cell mass cells (39.50 vs. 25.33, P < 0.05) were also significantly higher in the FLI group than in the control group. Evaluation of maternal gene expression revealed that FLI could significantly increase the expression levels of DNMT1, ZAR1, and NLRP5 and cumulus cell expansion genes PTX3, TNFAIP6, PTGS2, and HAS2 in mature oocytes (P < 0.01). We indirectly proved that bFGF, LIF, and IGF-1 support goat oocyte maturation and early embryonic development. In summary, this study established a reliable and efficient in vitro goat oocyte maturation culture system using bFGF, LIF, and IGF-1. The results of this study can serve as a technical basis for improving the quality of goat oocytes matured in vitro, potential of early embryonic development, IVF of goat embryos, and in vitro production of other livestock.