This study aims to investigate the expression of Pentraxin 3 (PTX3) and Nod-like receptor family pyrin domain-containing 3 (NLRP3) in myocarditis and to elucidate their roles and potential interplay in the pathogenesis of myocarditis.

Immunofluorescence staining was performed on myocardial autopsy specimens from deceased patients with severe myocarditis or severe trauma. H9C2 cardiomyocytes were divided into five groups: Control, Lipopolysaccharide (LPS), LPS + PTX3 overexpression, LPS + small interfering RNA targeting PTX3 (si-PTX3), and LPS + PTX3 overexpression + si-NLRP3. The expression levels of PTX3 and NLRP3 at the RNA level were quantified using quantitative real-time polymerase chain reaction (qPCR), while protein expression was assessed via western blot. The concentrations of interleukin-1β (IL-1β) and IL-18 were determined by enzyme-linked immunosorbent assay (ELISA). Macrophages migration was evaluated using Transwell assays.

Immunofluorescence staining revealed co-localization and increased expression of PTX3 and NLRP3 in the myocardium of patients with severe myocarditis. In vitro experiments demonstrated that PTX3 enhanced the expression of NLRP3, IL-1β, and IL-18 in LPS-stimulated cardiomyocytes. Furthermore, PTX3 was shown to promote macrophage migration by regulating NLRP3 expression, as assessed by Transwell assays.

Our findings suggest that PTX3-mediated NLRP3 activation contributes to inflammatory responses and promotes macrophage migration in myocarditis. This study provides a foundation for future investigations into PTX3-targeted therapies for myocarditis.

Pentraxin-3 (PTX3) is a soluble pattern recognition molecule (PRM) characterized by a C-terminal pentraxin structural domain and a unique N-terminal structural domain. As a key component of the innate immune system, PTX3 can be rapidly released into the extracellular space during microbial invasion and inflammatory responses. It plays a crucial role in regulating complement activation, enhancing the ability of myeloid cells to recognize pathogens, and exerting various immune effects. PTX3 is integral to the regulation of innate immunity, inflammation, and tumor dynamics through its dual function as both a pro-inflammatory and anti-inflammatory mediator depending on the context. This role is closely linked to its diverse molecular and cellular targets. Additionally, PTX3 has been implicated in the pathogenesis of various lung diseases through its involvement in numerous physiological and pathological processes. In this paper, we summarize the complex immunological functions of PTX3 and review the multifaceted roles it plays in the development of infectious lung diseases. Our objective is to highlight the potential for clinical targeting of PTX3 as a biomarker in infectious diseases and to propose it as a viable alternative in future therapeutic strategies.

Proteinogram is a semiquantitative method specially used in clinic to separate the serum proteins from patients for use in the diagnosis of diseases. However, this methodology has only been applied very recently with this approach in farmed fish. Thus, the aim of this study was to explore the changes in the serum proteinogram of gilthead seabream (Sparus aurata), after triggering an acute or chronic sterile inflammation. For this, two experiments were carried out: i) Acute inflammation experiment: seabream specimens were injected intramuscularly with 50 μL of λ-carrageenan (0.5 mg fish-1) or buffer (control) and blood samples were collected at 3, 6 and 24 h post-injection; ii) Chronic inflammation experiment: specimens were injected at 0, 7 and 14 days with 500, 250 and 250 μL of λ-carrageenan, respectively (20 mg fish-1) or buffer, and blood samples were collected at 15 days post-injection. In both cases, serum was obtained and processed by electropherograms and HPLC-mass spectrometry. Results of electropherograms of control fish revealed four major proteins of 19.5, 76.3, 104.4, and 156.7 kDa in the serum. These four proteins were correlated with apolipoprotein A-II (II (the counterpart of mammalian albumin, Apo fraction), serotransferrin (β fraction), inter-α-trypsin inhibitor heavy chain H3-like (α1 fraction) and α-2-macroglobulin-like (α2 fraction) according to the results obtained with HPLC-mass spectrometry. In a statistical view (p < 0.05), no variations were detected in the four major serum protein bands between the control and the acutely inflamed groups. However, in chronically inflamed fish, the Apo fraction decreased statistically compared to the control group. In contrast, the α1 and α2 fractions were statistically increased in the serum of fish sampled 15 days after λ-carrageenan injection, compared to those found in the control fish. α1 and α2 protein fractions are recognized indicators of inflammation in mammals. Consequently, our study presents a novel method for assessing both acute and chronic λ-carrageenan-induced sterile inflammation in gilthead seabream, which could be applicable to other marine species for diagnostic purposes.

Understanding the relationship between reproductive health and kidney function is important to provide holistic care for people living with kidney disease. Chronic kidney disease (CKD) has negative impacts on both male and female fertility owing to factors including inflammation, hormonal dysregulation, reduced ovarian reserve, reduced sperm quality and sexual dysfunction. However, pregnancy is achievable for most cisgender women with kidney disease, including kidney transplant recipients and patients on dialysis. CKD in pregnancy is associated with health risks to the mother and child, including increased risk of progression of kidney disease, hypertensive complications of pregnancy, and neonatal complications including fetal growth restriction, preterm birth and stillbirth. However, with appropriate pre-pregnancy counselling, fertility assessment and support, health optimization, and evidence-based antenatal care, the majority of patients will achieve a good outcome. Medication safety should be reviewed before and during pregnancy and lactation, weighing the risk of disease flare against potential adverse effects on the offspring. Important areas for further research include the optimal timing of delivery and the short- and long-term cardiovascular and renal impacts of pregnancy in patients with CKD, as well as long-term kidney and cardiovascular outcomes in their offspring.

Pediatric CNS infections have been identified as a global health problem, associated with an increased death rate and fatal consequences. Pentraxin 3 (PTX3) is an acute-phase mediator that increases in body fluids and plasma throughout inflammation. Our study was designed to assess the diagnostic and prognostic value of cerebrospinal fluid (CSF) PTX3 levels in pediatric patients with different central nervous system (CNS) infections.

We enrolled 100 children hospitalized at Fayoum University Children's Hospital with suspected CNS infections fulfilling the case criteria for CNS infections. We recorded their medical history and examination data upon admission. The C-reactive protein (CRP) level, complete blood count (CBC), CSF PTX3 level, CSF analysis and culture, and blood culture were assessed in all patients at the time of admission.

Levels of PTX3 were significantly correlated with the duration of symptoms before admission, length of hospital stay, patient outcomes, CRP levels, CSF findings, and CSF cultures (P value < 0.001). Patients who needed mechanical ventilation or experienced adverse outcomes had greater levels of PTX3, which were more prevalent in those with a bacterial etiology (P value < 0.05).

PTX3 indicates disease severity and prognosis. PTX3 showed statistically significant sensitivity when discriminating between bacterial and aseptic CNS infections, as well as between bacterial CNS infections and controls. However, it has lower sensitivity and specificity than other CSF biomarkers, though it is higher than serum CRP.

Chronic kidney disease (CKD) is a strong risk factor for cardiovascular mortality and morbidity. We hypothesized that a senescent phenotype instigated by uremic toxins could account for early vascular aging (EVA) and vascular dysfunctions of microvasculature in end stage kidney disease (ESKD) patients which ultimately lead to increased cardiovascular complication. To test this hypothesis, we utilized both in vivo, and ex vivo approaches to study endothelial and smooth muscle function and structure, and characterized markers related to EVA in 82 ESKD patients (eGFR <15 ml/min) and 70 non-CKD controls. In vivo measurement revealed no major difference in endothelial function between ESKD and control group, aside from higher stiffness detected in the microcirculation of ESKD participants. In contrast, ex vivo measurements revealed a notable change in the contribution of endothelium-derived factors and increased stiffness in ESKD patients vs. controls. In support, we demonstrated that ex vivo exposure of arteries to uremic toxins such as Trimethylamine N-oxide, Phenylacetylglutamine, or extracellular vesicles from CKD patients impaired endothelial function via diminishing the contribution of endothelium-derived relaxing factors such as nitric oxide and endothelium derived hyperpolarizing factor. Uremic arteries displayed elevated expression of senescence markers (p21CIP1, p16INK4a, and SA-β-gal), calcification marker (RUNX2), and reduced expression of Ki67, sirtuin1, Nrf2, and MHY11 markers, indicating the accumulation of senescent cells and EVA phenotype. Correspondingly, treating uremic vessel rings ex vivo with senolytic agents (Dasatinib + Quercetin) effectively reduced the senescence-associated secretory phenotype and changed the origin of extracellular vesicles. Notably, sex differences exist for certain abnormalities suggesting the importance of biological sex in the pathogenesis of vascular complications. In conclusion, the uremic microvasculature is characterized by a "senescence signature", which may contribute to EVA and cardiovascular complications in ESKD patients and could be alleviated by treatment with senolytic agents.

Non-alcoholic fatty liver disease is a globally prevalent disorder that can rapidly progress if not detected early. Currently, no accepted markers exist for early diagnosis and prognosis of NAFLD. This review describes derangement in major metabolic pathways of lipid, carbohydrate, and amino acids in NAFLD. It suggests that measuring levels of thrombospondin, TyG index, asymmetric dimethylarginine, LAL-A, GLP-1, FGF-21, and GSG index are potential markers for early diagnosis of NAFLD. A single marker may not indicate early NAFLD, and further large-scale studies on correlating levels of Thrombospondin-2, triglyceride-glucose index, and FGF-21 with NAFLD are warranted.

Macrophages, crucial components of the human immune system, can be polarized into M1/M2 phenotypes, each with distinct functions and roles. Macrophage polarization has been reported to be significantly involved in the inflammation and fibrosis observed in kidney injury. MicroRNA (miRNA), a type of short RNA lacking protein-coding function, can inhibit specific mRNA by partially binding to its target mRNA. The intricate association between miRNAs and macrophages has been attracting increasing interest in recent years. This review discusses the role of miRNAs in regulating macrophage-mediated kidney injury. It shows how miRNAs can influence macrophage polarization, thereby altering the biological function of macrophages in the kidney. Furthermore, this review highlights the significance of miRNAs derived from exosomes and extracellular vesicles as a crucial mediator in the crosstalk between macrophages and kidney cells. The potential of miRNAs as treatment applications and biomarkers for macrophage-mediated kidney injury is also discussed.

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.

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.

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.

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).

Pentraxin 3 (PTX3) is an acute phase protein produced in various tissues in response to microbial and sterile stimuli, which regulates the inflammation outcomes. PTX3 has not been investigated in myocarditis. Our aim was to assess circulating and cardiac tissue expression of PTX3 in 55 patients with myocarditis proven by magnetic resonance and/or endomyocardial biopsy. A major proportion of patients with myocarditis displayed significantly increased plasma PTX3 levels as compared with controls (26/30 vs. 0/10), with higher diagnostic yield than conventional biomarkers in the study group. Cardiac tissue analysis revealed PTX3 expression in all patients (40/40), with viral myocarditis exhibiting higher signal intensity than autoimmune myocarditis, and with a predominant localization in cardiomyocytes. Abnormal plasma PTX3 was associated with systolic dysfunction and heart failure at presentation. Interestingly, patients who recovered by 12 months had higher baseline PTX3 levels. Our preliminary data support the potential use of PTX3 as a biomarker in myocarditis.

Serum amyloid P component (SAP) is a member the innate immune humoral arm and participated in various processes, including the innate immune responses, tissue remodeling, and the pathogenesis of inflammatory diseases. Remarkably, SAP is a highly versatile immunomodulatory factor that can serve as a drug target for treating amyloid diseases and reduce inflammation, fibrosis degree, and respiratory disease. In this review, we focus on the biological activities of SAP and its application in different systemic immune-associated diseases. First, we reviewed the regulatory effects of SAP on innate immune cells and possible mechanisms. Second, we emphasized SAP as a diagnostic marker and therapeutic target for immune-associated diseases, including the neuropsychiatric disorders. Third, we presented several recommendations for regulating SAP in immune cell function and potential areas for future research. Some authorities consider SAP to be a pattern recognition molecule that plays multiple roles in the innate immune system and inflammation. Developing therapeutics that target SAP or its associated signaling pathways may be a promising strategy for treating immune-associated diseases.

This study aimed to investigate the regulatory mechanism of the adipose factor interleukin (IL)-6 in promoting pentraxin 3 (PTX3) expression in triple-negative breast cancer (TNBC).

We established an in vitro coculture model of mature adipocytes and TNBC cells using a Transwell system. Cell scratch, Transwell migration, and matrix invasion assays were used to evaluate the migration and invasion abilities of TNBC cells cocultured with adipocytes. Next, we used lentivirus-mediated functional depletion experiments to study PTX3's role in the adipocyte-dependent migration of TNBC cells.

After coculturing TNBC cells with adipocytes, PTX3 expression was upregulated, which accompanied enhanced cell migration and invasion. Using GEO data and RNA-seq analysis, we identified PTX3 as a key target gene influenced by the adipose TNBC microenvironment. IL-6 upregulation in the conditioned medium of mature adipocytes and in the serum of high-fat diet mice was associated with this effect, and the recombinant protein IL-6 significantly promoted the migration and invasion of TNBC cells along with the phosphorylation of intracellular STAT3 and the upregulation of PTX3. PTX3 knockdown inhibited TNBC cell migration and eliminated the enhanced migration caused by coculturing with adipocytes. Furthermore, in vivo experiments confirmed that the PTX3 knockdown reduced obesity-induced lung metastasis. Subsequent experiments with cytokines and drug inhibitors confirmed that adipocyte-derived IL-6 promoted PTX3 expression by activating the STAT3 signaling pathway. Additionally, bioinformatic analysis indicated that PTX3 promotes TNBC metastasis by regulating the matrix metalloproteinase (MMP) family.

Our study elucidated Obesity-related metabolic inflammation promotes the progression via the IL-6/STAT3/PTX3/MMP7 axis.

Sepsis poses a significant threat to human health due to its high morbidity and mortality rates worldwide. Traditional diagnostic methods for identifying sepsis or its causative organisms are time-consuming and contribute to a high mortality rate. Biomarkers have been developed to overcome these limitations and are currently used for sepsis diagnosis, prognosis prediction, and treatment response assessment. Over the past few decades, more than 250 biomarkers have been identified, a few of which have been used in clinical decision-making. Consistent with the limitations of diagnosing sepsis, there is currently no specific treatment for sepsis. Currently, the general treatment for sepsis is conservative and includes timely antibiotic use and hemodynamic support. When planning sepsis-specific treatment, it is important to select the most suitable patient, considering the heterogeneous nature of sepsis. This comprehensive review summarizes current and evolving biomarkers and therapeutic approaches 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.

C-reactive protein (CRP) is a plasma protein that is evolutionarily conserved, found in both vertebrates and many invertebrates. It is a member of the pentraxin superfamily, characterized by its pentameric structure and calcium-dependent binding to ligands like phosphocholine (PC). In humans and various other species, the plasma concentration of this protein is markedly elevated during inflammatory conditions, establishing it as a prototypical acute phase protein that plays a role in innate immune responses. This feature can also be used clinically to evaluate the severity of inflammation in the organism. Human CRP (huCRP) can exhibit contrasting biological functions due to conformational transitions, while CRP in various species retains conserved protective functions in vivo. The focus of this review will be on the structural traits of CRP, the regulation of its expression, activate complement, and its function in related diseases in vivo.

Pentraxins (PTXs) are a family of pattern recognition proteins (PRPs) that play a role in pathogen recognition during infection via pathogen-associated molecular patterns (PAMPs). Here, we characterized a short-chained pentraxin isolated from kuruma shrimp (Marsupenaeus japonicus) hemocytes (MjPTX). MjPTX contains the pentraxin signature HxCxS/TWxS (where x can be any amino acid), although the second conserved residue of this signature differed slightly (L instead of C). In the phylogenetic analysis, MjPTX clustered closely with predicted sequences from crustaceans (shrimp, lobster, and crayfish) displaying high sequence identities exceeding 52.67 %. In contrast, MjPTX showed minimal sequence identity when compared to functionally similar proteins in other animals, with sequence identities ranging from 20.42 % (mouse) to 28.14 % (horseshoe crab). MjPTX mRNA transcript levels increased significantly after artificial infection with Vibrio parahaemolyticus (48 h), White Spot Syndrome Virus (72 h) and Yellow Head Virus (24 and 48 h). Assays done in vitro revealed that recombinant MjPTX (rMjPTX) has an ability to agglutinate Gram-negative and Gram-positive bacteria and to bind microbial polysaccharides and bacterial suspensions in the presence of Ca2+. Taken together, our results suggest that MjPTX functions as a classical pattern recognition protein in the presence of calcium ions, that is capable of binding to specific moieties present on the surface of microorganisms and facilitating their clearance.

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.

Chronic limb-threatening ischemia (CLTI), the advanced stage of peripheral arterial disease, is diagnosed in the presence of ischemic rest pain, non-healing ulcers, or gangrene. Several studies have demonstrated that inflammation and endothelial dysfunction are some of the main substrates of CLTI.

A narrative review was conducted and reported according to PRISMA guidelines. Three databases were searched-Web of Science, Medline, and EMBASE-for the studies assessing CLTI and the biological markers related to it.

We included 22 studies, and all the markers identified (C-reactive protein, D-dimers, fibrinogen, cytokines, IL-6, TNF-α, ICAM-1 (Intracellular Adhesion Molecule-1), VCAM-1 (Vascular Cell Adhesion Molecule-1), neutrophile-to-lymphocytes ratio (NLR), IL-8, Pentraxin-3, neutrophil gelatinase-associated lipocalin (NGAL), calprotectin, E-selectin, P-selectin, neopterin, High-Mobility Group Box-1 protein (HGMB-1), Osteoprotegerin (OPG) and Sortilin) were positively associated with advanced CLTI, with major limb or major cardiovascular events in these patients.

All the studied markers had increased values in patients with CLTI, especially when associated with diabetes mellitus, proving a very important association between diabetes and major limb or cardiovascular events in these patients. There is a need for more studies to validate these markers in terms of diagnosis or prognosis in CLTI patients and in trying to find new medical strategies that target inflammation or endothelial dysfunction in these patients.

Neuronal pentraxin 2 (Nptx2), a member of the synaptic protein family linked to excitatory synaptic formation, is found to be upregulated in epileptic mice, yet its role in epilepsy has been unclear. In vivo, we constructed a mouse model of epilepsy by using kainic acid induction. In vitro experiments, a Mg2+-free medium was used to induce epileptiform discharges in neurons. The results showed that the Nptx2 was upregulated in epileptic mice. Moreover, Nptx2 knockdown reduced the number of seizures and seizure duration. Knocking down Nptx2 not only reduced the number and duration of seizures but also showed a decrease in electroencephalogram amplitude. Behavioral tests indicated improvements in learning and memory abilities after Nptx2 knockdown. The Nissl staining and Timms staining revealed that Nptx2 silencing mitigated epilepsy-induced brain damage. The immunofluorescence staining revealed that Nptx2 absence resulted in a reduction of apoptosis. Nptx2 knockdown reduced Bax, cleaved caspase3, and cleaved caspase9 expression, while increased Bcl-2 expression. Notably, Nptx2 knockdown inhibited GluA1 phosphorylation at the S831 site and reduced the GluA1 membrane expression. The PSD95 expression declined in the epilepsy model, while the Nptx2 knockdown reversed it. Collectively, our study indicated that Nptx2 silencing not only alleviated brain damage and neuron apoptosis but also improved learning and memory ability in epileptic mice, suggesting Nptx2 as a promising target for epilepsy treatment.

Understanding the immune response to Aspergillus fumigatus, a common cause of invasive fungal infections (IFIs) in immunocompromised individuals, is critical for developing effective treatments. Tcells play a critical role in the immune response to A. fumigatus, with different subsets having distinct functions. Th1 cells are important for controlling fungal growth, while Th2 cells can exacerbate infection. Th17 cells promote the clearance of fungi indirectly by stimulating the production of various antimicrobial peptides from epithelial cells and directly by recruiting and activating neutrophils. Regulatory T cells have varied functions in A.fumigatus infection. They expand after exposure to A. fumigatus conidia and prevent organ injury and fungal sepsis by downregulating inflammation and inhibiting neutrophils or suppressing Th17 cells. Regulatory T cells also block Th2 cells to stop aspergillosis allergies. Immunotherapy with CAR T cells is a promising treatment for fungal infections, including A. fumigatus infections, especially in immunocompromised individuals. However, further research is needed to fully understand the mechanisms underlying the immune response to A. fumigatus and to develop effective immunotherapies with CAR-T cells for this infection. This literature review explores the role of Tcell subsets in A.fumigatus infection, and the effects of CAR-T cell therapy on this fungal infection.

Human immunodeficiency virus (HIV) infection causes chronic inflammation in affected individuals. Chronic inflammation may hinder immunological recovery. Treatment with combination antiretroviral therapy (cART) is insufficient to reduce inflammation. Pentraxin 3 (PTX3) is an inflammatory marker associated with cardiovascular disease, malignancy, and acute infection. This study evaluated the usefulness of serum PTX3 levels in measuring inflammation levels, which may be associated with the probability of immune recovery in people living with HIV (PLH). In this single-center prospective study, we measured serum PTX3 levels in PLH treated with cART. Clinical information on HIV status, type of cART administered, and CD4+ and CD8+ T cell counts at the initial diagnosis of HIV and at study enrollment was obtained from each participant. PLH were divided into good and poor responder groups according to their CD4+ T cell counts at enrollment. A total of 198 PLH were enrolled in this study. A total of 175 and 23 participants were assigned to the good and poor responder groups, respectively. The poor responder group exhibited higher PTX3 levels (0.53 ng/mL vs. 1.26 ng/mL, p = .032). Logistic regression analysis demonstrated that low body mass index [odds ratio (OR) = 0.8, p = .010], low initial CD4+ T cell counts at diagnosis (OR = 0.994, p = .001), and high PTX3 levels (OR = 1.545, p = .006) are clinical factors that were significantly associated with poor immune recovery in PLH. According to the Youden index, PTX3 levels >1.25 ng/mL are associated with poor immune recovery. PLH should be clinically, virologically, and immunologically evaluated. Serum PTX level is a useful inflammatory marker associated with immune recovery in PLH treated with cART.

Cardiovascular disease (CVD) is the primary global cause of death, and inflammation is a crucial factor in the development of CVDs. The acute phase inflammatory protein pentraxin 3 (PTX3) is a biomarker reflecting the immune response. Recent research indicates that PTX3 plays a vital role in CVDs and has been investigated as a possible biomarker for CVD in clinical trials. PTX3 is implicated in the progression of CVDs through mechanisms such as exacerbating vascular endothelial dysfunction, affecting angiogenesis, and regulating inflammation and oxidative stress. This review summarized the structure and function of PTX3, focusing on its multifaceted effects on CVDs, such as atherosclerosis, myocardial infarction, and hypertension. This may help in explaining the varying PTX3 functions and usage, as well as in utilizing target organs to manage diseases. Moreover, elucidating the opposite role of PTX3 in the cardiovascular system will demonstrate the therapeutic and predictive potential in human diseases.

Zinpentraxin alfa is a recombinant human pentraxin-2 (PTX-2) developed for the treatment of various fibrotic diseases with the hypothesis that supplementing endogenous PTX-2 levels through intravenous administration should increase its regulatory capacity in circulation and at the site of disease, thereby promoting healing and reducing fibrosis. Zinpentraxin alfa has been studied in various clinical trials, particularly in patients with idiopathic pulmonary fibrosis, where it has demonstrated efficacy in slowing decline in lung function in a phase 2 study. In the present investigation, we summarize findings from 14-day repeat-dose toxicity studies in rats and cynomolgus monkeys supporting early clinical development of zinpentraxin alfa. In addition, we also describe the findings from the embryo-fetal developmental (EFD) studies conducted in rats and rabbits, since the intended fibrosis patient population may include patients of childbearing potential. Zinpentraxin alfa was well tolerated by rats and monkeys in general toxicity studies with no treatment-related adverse effects, as well as by pregnant rats over the same dose range in a definitive EFD study. In contrast, substantial toxicity was observed in a rabbit dose-range-finder EFD study. Zinpentraxin alfa was poorly tolerated by pregnant rabbits and effects on the dams correlated with post-implantation fetal losses. The disparate effects of zinpentraxin alfa on embryo-fetal development between the two species suggests a potential unknown biological function of PTX-2 in pregnancy in the rabbit, which may be relevant to humans. Our findings warrant the consideration for highly effective contraceptive measures to avoid pregnancy in patients enrolled in clinical studies with zinpentraxin alfa.

Myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia, and myelofibrosis, are characterized by somatic gene mutations in bone marrow stem cells, which trigger an inflammatory response influencing the development of associated cardiovascular complications. In recent years, the same mutations were found in individuals with cardiovascular diseases even in the absence of hematological alterations. These genetic events allow the identification of a new entity called 'clonal hematopoiesis of indeterminate potential' (CHIP), as it was uncertain whether it could evolve toward hematological malignancies. CHIP is age-related and, remarkably, myocardial infarction, stroke, and heart failure were frequently reported in these individuals and attributed to systemic chronic inflammation driven by the genetic mutation. We reviewed the connection between clonal hematopoiesis, inflammation, and cardiovascular diseases, with a practical approach to improve clinical practice and highlight the current unmet needs in this area of knowledge.

The complement is a crucial immune defense system that triggers rapid immune responses and offers efficient protection against foreign invaders and unwanted host elements, acting as a sentinel. Activation of the complement system occurs upon the recognition of pathogenic microorganisms or altered self-cells by pattern-recognition molecules (PRMs) such as C1q, collectins, ficolins, and pentraxins. Recent accumulating evidence shows that pentraxins establish a cooperative network with different classes of effector PRMs, resulting in synergistic effects in complement activation. This review describes the complex interaction of pentraxins with the complement system and the implications of this cooperative network for effective host defense during pathogen invasion.

Idiopathic pulmonary fibrosis (IPF) is a progressive fatal interstitial lung disease that affects three million patients worldwide and currently without an effective cure. Zinpentraxin alfa, a recombinant human pentraxin-2 (rhPTX-2) protein, has been evaluated as a potential drug candidate for the treatment of IPF. Clinical pharmacokinetic analysis of zinpentraxin alfa has been challenging historically due to interference from serum amyloid P component (SAP), an endogenous human pentraxin-2 protein. These molecules share an identical primary amino acid sequence and glycan composition; however, zinpentraxin alfa possesses α2,3-linked terminal sialic acid residues while SAP is an α2,6-linked isomer. By taking advantage of this only structural difference, we developed a novel assay strategy where α2,3-sialidase was used to selectively hydrolyze α2,3-linked sialic acid residues, resulting in desialylated zinpentraxin alfa versus unchanged sialylated SAP, following an immunoaffinity capture step. Subsequent tryptic digestion produced a unique surrogate asialo-glycopeptide from zinpentraxin alfa and allowed specific quantification of the biotherapeutic in human plasma. In addition, a common peptide shared by both molecules was selected as a surrogate to determine total hPTX-2 concentrations, i.e., sum of zinpentraxin alfa and SAP. The quantification methods for both zinpentraxin alfa and total hPTX-2 were validated and used in pharmacokinetic assessment in IPF patients. The preliminary results suggest that endogenous SAP levels remained largely constant in IPF patients throughout the treatment with zinpentraxin alfa. Our novel approach provides a general bioanalytical strategy to selectively quantify α2,3-sialylated glycoproteins in the presence of their corresponding α2,6-linked isomers.

Chronic stress deteriorates the immune function of fish, thereby increasing their vulnerability to infections. However, the molecular and cellular mechanisms underlying stress-mediated immunosuppression and infection susceptibility in fish remain largely unknown. Understanding these mechanisms will contribute to improving fish welfare and their farm production. Herein, we review the challenges of sturgeon aquaculture in subtropical countries, where current climate change has giving rise to significant temperature increments during summer. This leads to the exposure of fish to stressful conditions during these months. Chronic heat stress deserves attention considering the rapid warming rate of the planet. It is already affecting wild fish populations, with disastrous consequences for sturgeons, which are one of the most endangered fish species in the world. In this context, we discuss the most recent advances through the studies on the effects of chronic heat stress on the innate immune components of sturgeons. To this end, we summarise the findings of studies focusing on the aquaculture of Russian sturgeons and observations made on other Acipenser species. Special attention is given to acute-phase proteins, as they might be valuable biomarkers of heat stress and infection, with applicability in monitoring the fish health status in farms.

Pentraxin-3 (PTX3) is a component of humoral innate immunity with essential functions both in promotion and resolution of inflammation. We aimed to study the PTX3 in the plasma and in the muscle of patients with idiopathic inflammatory myopathies (IIM) and whether PTX3 may correlate with disease activity. Plasma PTX3 levels were assessed in 20 patients with IIMs, 10 dermatomyositis (DM), and 10 polymyositis (PM), compared to 10 patients with rheumatoid arthritis (RA) and 10 healthy donors (HDs) aged, sex, and body mass index matched. Disease activity in IIMs was assessed by Myositis Disease Activity Assessment Visual Analog Scale (MYOACT), while disease activity score on 28 joints (DAS28) was used for RA patients. Muscle histopathology and immunohistochemical (IHC) analyses were also performed. Mean plasma PTX3 levels were significantly higher in IIM patients than HDs (518 ± 260 pg/ml vs. 275 ± 114 pg/ml, P = 0.009). Linear regression analysis adjusted for age, sex, and disease duration showed a direct correlation between PTX3 and CPK levels (β: 0.590), MYOACT (β: 0.759), and physician global assessment of disease activity (β: 0.832) in IIMs. No association between PTX3 levels and DAS28 was found in RA. Global PTX3 pixel fraction was higher in IIM than HDs muscle, but a lower PTX3 expression was found in perifascicular areas of DM and in myofibers with sarcolemmal staining for membrane attack complement. PTX3 plasma levels were increased in IIMs and correlated with disease activity suggesting a possible role as biomarker of disease activity. PTX3 showed a different distribution in DM or PM muscle.

The immune system is divided into two broad categories, consisting of innate and adaptive immunity. As recognition and effector factors of innate immunity and regulators of adaptive immune responses, lectins are considered to be important defense chemicals against microbial pathogens, cell trafficking, immune regulation, and prevention of autoimmunity. Pentraxins, important members of animal lectins, play a significant role in protecting the body from pathogen infection and regulating inflammatory reactions. They can recognize and bind to a variety of ligands, including carbohydrates, lipids, proteins, nucleic acids and their complexes, and protect the host from pathogen invasion by activating the complement cascade and Fcγ receptor pathways. Based on the primary structure of the subunit, pentraxins are divided into short and long pentraxins. The short pentraxins are comprised of C-reactive protein (CRP) and serum amyloid P (SAP), and the most important member of the long pentraxins is pentraxin 3 (PTX3). The CRP and SAP exist in both vertebrates and invertebrates, while the PTX3 may be present only in vertebrates. The major ligands and functions of CRP, SAP and PTX3 and three activation pathways involved in the complement system are summarized in this review. Their different characteristics in various animals including humans, and their evolutionary trees are analyzed. The clinical applications of CRP, SAP and PTX3 in human are reviewed. Some questions that remain to be understood are also highlighted.

Pentraxin 3 (PTX3) is a soluble pattern recognition molecule in the innate immune system that has multiple functions. It is involved in resisting pathogen infection. However, the functions of PTX3 in teleost fish are not well understood. In this study, we identified and characterized PTX3 in Nile tilapia (Oreochromis niloticus) (OnPTX3). The open reading frame of OnPTX3 was found to be 1305 bp, encoding 434 aa. We conducted spatial mRNA expression analysis and found that the expression of OnPTX3 was significantly increased after infection with Streptococcus agalactiae and Aeromonas hydrophila, both in vivo and in vitro. We also observed that recombinant OnPTX3 protein could bind and agglutinate bacterial pathogen. Furthermore, OnPTX3 enhanced the phagocytosis of bacteria (S. agalactiae and A. hydrophila) by head kidney macrophages. Additionally, OnPTX3 was found to influence the expression of inflammatory cytokines, suggesting its involvement in the regulation of the inflammatory response. Moreover, OnPTX3 was shown to promote complement-mediated hemolysis and possess antibacterial activity. In conclusion, our research demonstrates that OnPTX3 has bacterial binding and agglutination activities, enhances phagocytosis, and regulates inflammation. It plays a crucial role in the defense of Nile tilapia against pathogenic bacteria, providing valuable insights for the prevention and control of aquatic diseases in the future.

Fetal death is a complication of pregnancy caused by multiple etiologies rather than being the end-result of a single disease process. Many soluble analytes in the maternal circulation, such as hormones and cytokines, have been implicated in its pathophysiology. However, changes in the protein content of extracellular vesicles (EVs), which could provide additional insight into the disease pathways of this obstetrical syndrome, have not been examined. This study aimed to characterize the proteomic profile of EVs in the plasma of pregnant women who experienced fetal death and to evaluate whether such a profile reflected the pathophysiological mechanisms of this obstetrical complication. Moreover, the proteomic results were compared to and integrated with those obtained from the soluble fraction of maternal plasma.

This retrospective case-control study included 47 women who experienced fetal death and 94 matched, healthy, pregnant controls. Proteomic analysis of 82 proteins in the EVs and the soluble fractions of maternal plasma samples was conducted by using a bead-based, multiplexed immunoassay platform. Quantile regression analysis and random forest models were implemented to assess differences in the concentration of proteins in the EV and soluble fractions and to evaluate their combined discriminatory power between clinical groups. Hierarchical cluster analysis was applied to identify subgroups of fetal death cases with similar proteomic profiles. A p-value of <.05 was used to infer significance, unless multiple testing was involved, with the false discovery rate controlled at the 10% level (q < 0.1). All statistical analyses were performed by using the R statistical language and environment-and specialized packages.

Nineteen proteins (placental growth factor, macrophage migration inhibitory factor, endoglin, regulated upon activation normal T cell expressed and presumably secreted (RANTES), interleukin (IL)-6, macrophage inflammatory protein 1-alpha, urokinase plasminogen activator surface receptor, tissue factor pathway inhibitor, IL-8, E-Selectin, vascular endothelial growth factor receptor 2, pentraxin 3, IL-16, galectin-1, monocyte chemotactic protein 1, disintegrin and metalloproteinase domain-containing protein 12, insulin-like growth factor-binding protein 1, matrix metalloproteinase-1(MMP1), and CD163) were found to have different plasma concentrations (of an EV or a soluble fraction) in women with fetal death compared to controls. There was a similar pattern of change for the dysregulated proteins in the EV and soluble fractions and a positive correlation between the log2-fold changes of proteins significant in either the EV or the soluble fraction (ρ = 0.89, p < .001). The combination of EV and soluble fraction proteins resulted in a good discriminatory model (area under the ROC curve, 82%; sensitivity, 57.5% at a 10% false-positive rate). Unsupervised clustering based on the proteins differentially expressed in either the EV or the soluble fraction of patients with fetal death relative to controls revealed three major clusters of patients.

Pregnant women with fetal death have different concentrations of 19 proteins in the EV and soluble fractions compared to controls, and the direction of changes in concentration was similar between fractions. The combination of EV and soluble protein concentrations revealed three different clusters of fetal death cases with distinct clinical and placental histopathological characteristics.

The pentraxins represent a family of multifunctional proteins composed of long and short pentamers. The latter includes serum amyloid P component (SAP) and C-reactive protein (CRP) whereas the former includes neuronal PTX1 and PTX2 (NPTX1 and NPTX2, respectively), PTX3 and PTX4. These serve as a bridge between adaptive immunity and innate immunity and a link between inflammation and immunity. Similarities and differences between long and short pentamers are examined and their roles in autoimmune disease are discussed. Increased CRP and PTX3 could indicate the activity of rheumatoid arthritis, systemic lupus erythematosus or other autoimmune diseases. Mechanistically, CRP and PTX3 may predict target organ injury, regulate bone metabolic immunity and maintain homeostasis as well as participate in vascular endothelial remodeling. Interestingly, PTX3 is pleiotropic, being involved in inflammation and tissue repair. Given the therapeutic potential of PTX3 and CRP, targeting these factors to exert a beneficial effect is the focus of research efforts. Unfortunately, studies on NPTX1, NPTX2, PTX4 and SAP are scarce and more research is clearly needed to elaborate their potential roles in autoimmune disease.

The major barrier to an HIV cure is the HIV reservoir: latently-infected cells that persist despite effective antiretroviral therapy (ART). There have been few cohort-based studies evaluating host genomic or transcriptomic predictors of the HIV reservoir. We performed host RNA sequencing and HIV reservoir quantification (total DNA [tDNA], unspliced RNA [usRNA], intact DNA) from peripheral CD4+ T cells from 191 ART-suppressed people with HIV (PWH). After adjusting for nadir CD4+ count, timing of ART initiation, and genetic ancestry, we identified two host genes for which higher expression was significantly associated with smaller total DNA viral reservoir size, P3H3 and NBL1, both known tumor suppressor genes. We then identified 17 host genes for which lower expression was associated with higher residual transcription (HIV usRNA). These included novel associations with membrane channel (KCNJ2, GJB2), inflammasome (IL1A, CSF3, TNFAIP5, TNFAIP6, TNFAIP9, CXCL3, CXCL10), and innate immunity (TLR7) genes (FDR-adjusted q<0.05). Gene set enrichment analyses further identified significant associations of HIV usRNA with TLR4/microbial translocation (q = 0.006), IL-1/NRLP3 inflammasome (q = 0.008), and IL-10 (q = 0.037) signaling. Protein validation assays using ELISA and multiplex cytokine assays supported these observed inverse host gene correlations, with P3H3, IL-10, and TNF-α protein associations achieving statistical significance (p<0.05). Plasma IL-10 was also significantly inversely associated with HIV DNA (p = 0.016). HIV intact DNA was not associated with differential host gene expression, although this may have been due to a large number of undetectable values in our study. To our knowledge, this is the largest host transcriptomic study of the HIV reservoir. Our findings suggest that host gene expression may vary in response to the transcriptionally active reservoir and that changes in cellular proliferation genes may influence the size of the HIV reservoir. These findings add important data to the limited host genetic HIV reservoir studies to date.

Zinpentraxin alfa (rhPTX-2; PRM-151) is currently being developed for the treatment of fibrotic diseases such as idiopathic pulmonary fibrosis and myelofibrosis. Notably, because it is administered chronically and has an endogenously expressed counterpart, clinical studies of zinpentraxin alpha must include immunogenicity assessments. Since the typical homogenous bridging ELISA assay does not adequately measure anti-drug antibodies (ADAs) against zinpentraxin alfa, additional assay formats have been developed to evaluate immunogenicity of this therapeutic. Here, we present the evaluation of four distinct assay formats that were used to measure zinpentraxin alpha ADA: step-wise bridging, direct binding, total ADA, and the semi-homogeneous formats, based on multiple parameters including assay sensitivity, precision, and drug tolerance. This paper presents the full details of method development for each of the aforementioned assay formats including evaluation of sample pre-treatment, determination of cut point, and assessment of assay performance by analyzing a subset of clinical samples. Overall, the semi-homogenous ADA assay format with no sample pre-treatment was selected for the measurement of zinpentraxin alpha immunogenicity as it provided the desired sensitivity, drug tolerance, and reproducibility. Our study emphasizes the importance of assay format evaluation during drug development and the necessity to select the most suitable assay format and sample pre-treatment method by which to evaluate therapeutic drug immunogenicity.

Renal fibrosis is the common pathological feature of various chronic kidney diseases (CKD). Tubular cell senescence plays a key role in the progression of renal fibrosis. However, the underlying mechanisms are still in mystery. In this study, we identified, Pentraxin 3 (PTX3), belonging to the Pentraxin family, is a new fibrogenic factor. PTX3 was increased in various CKD models. PTX3 was primarily localized in tubular epithelial cells and upregulated, accompanied by mitochondrial dysfunction and cellular senescence. Overexpression of PTX3 aggravated mitochondrial damage and accelerated cell senescence in tubular cells, leading to more severe fibrogenesis in kidneys. However, knockout of PTX3 significantly preserved mitochondrial homeostasis, and blocked cellular senescence in primary cultured tubular cells. Furthermore, KYA1797K, a destabilizer of β-catenin, greatly inhibited PTX3-induced mitochondrial dysfunction, tubular cell senescence, and renal fibrosis. Overexpression of PTX3 triggered nuclear translocation of β-catenin, an activating form of β-catenin. PTX3-induced mitochondrial dysfunction and tubular cell senescence were also significantly inhibited by knockdown of p16INK4A, a senescence-related protein. In a clinical cohort, we found PTX3 was increased in urine and serum in patients with CKD. Urinary PTX3 negatively correlated with eGFR. PTX3 also increased gradually following the severity of diseases, triggering the fibrogenesis. Taken together, our results provide strong evidences that PTX3 is a new fibrogenic factor in the development of renal fibrosis through β-catenin-induced mitochondrial dysfunction and cell senescence. This study further suggests PTX3 is a new diagnostic factor to renal fibrosis and provides a new therapeutic target against renal fibrosis.

Glioma is the most common and fatal type of brain tumour. Owing to its aggressiveness and lethality, early diagnosis and prediction of patient survival are very important. This study aimed to identify key genes and biomarkers for glioma that can guide clinicians in making rapid diagnosis and prognostication.

Data mining of The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Repository of Molecular Brain Neoplasia Data, and Genotype-Tissue Expression Project brain expression data revealed significantly differentially expressed genes (DEGs), and the risk scores of individual patients were calculated. WGCNA was utilized to screen for genes most related to clinical diagnosis. Prognostic genes associated with glioma were selected via combining the LASSO regression with univariate and multivariate Cox regression and protein-protein interaction network analyses. Then, a nomogram was constructed. And CGGA dataset was utilized to validated. The protein expression levels of the signature were detected using the human protein atlas. Drug response prediction was carried out using the package "pRRophetic".

A six-gene signature (KLF6, CHI3L1, SERPINE1, ANGPT2, TGFBR1, and PTX3) was identified and used to stratify patients into low- and high-risk groups. Survival, ROC curve, and Cox analyses clarified that the six hub genes were a favourable independent prognostic factor for patients with glioma. A nomogram was set up by integrating clinical parameters with risk signatures, showing high precision for predicting 2-, 3-, 4-, 5-years survival. In addition, the expression of most genes was consistent with protein expression. Furthermore, the sensitivity to the top ten drugs in the GDSC database of the high-risk group was significantly higher than the low-risk group.

Based on genetic profiles and clinicopathological features, including age, grade, isocitrate dehydrogenase mutation status, we constructed a comprehensive prognostic model for patients with glioma. These signatures can be regarded as biomarkers to predict the prognosis of gliomas, possibly providing more therapeutic strategies for future clinical research.