The structural organisation of pentraxin-3 and its interactions with heavy chains of inter-α-inhibitor regulate crosslinking of the hyaluronan matrix

Matrix Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Pentraxin-3 (PTX3) is an octameric protein, comprised of eight identical protomers, that has diverse functions in reproductive biology, innate immunity and cancer. PTX3 interacts with the large polysaccharide hyaluronan (HA) to which heavy chains (HCs) inter-α-inhibitor (IαI) family proteoglycans are covalently attached, playing a key role (non-covalent) crosslinking HC•HA complexes. These interactions stabilise cumulus matrix, essential for ovulation fertilisation mammals, also implicated formation pathogenic matrices context viral lung infections. To better understand physiological pathological roles we have analysed how its quaternary structure underpins HA via HCs. A combination X-ray crystallography, cryo-electron microscopy (cryo-EM) AlphaFold predictive modelling revealed C-terminal pentraxin domains octamer arranged central cube, two long extensions on either side, each formed from four protomers assembled into tetrameric coiled-coil regions, essentially as described by (Noone et al., 2022; doi:10.1073/pnas.2208144119). From crystallography cryo-EM data, identified network inter-protomer salt bridges facilitate assembly octamer. Small angle scattering (SAXS) validated our model including analysis constructs: 'Half-PTX3' construct missing 24 N-terminal residues (Δ1-24-PTX3). SAXS determined length ∼520 Å and, combined 3D variability defined flexibility extensions. Biophysical analyses prototypical chain HC1 does not interact at pH 7.4, consistent previous studies showing that, this pH, only associates complexes if they presence. However, binds acidic can be incorporated pre-formed under these conditions. This provides novel mechanism regulation PTX3-mediated (e.g., during inflammation), likely mediated pH-dependent conformational change HC1. The was found associate simultaneously up molecules thus, potential form major node within matrices, i.e., where physical biochemical properties resulting could tuned HC/PTX3 composition.

Language: Английский

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Machine learning-based investigation of regulated cell death for predicting prognosis and immunotherapy response in glioma patients

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Feb. 20, 2024

Abstract Glioblastoma is a highly aggressive and malignant type of brain cancer that originates from glial cells in the brain, with median survival time 15 months 5-year rate less than 5%. Regulated cell death (RCD) autonomous orderly under genetic control, controlled by precise signaling pathways molecularly defined effector mechanisms, modulated pharmacological or interventions, plays key role maintaining homeostasis internal environment. The comprehensive systemic landscape RCD glioma not fully investigated explored. After collecting 18 RCD-related signatures opening literature, we comprehensively explored landscape, integrating multi-omics data, including large-scale bulk single-cell level lines, proteome data. We also provided machine learning framework for screening potentially therapeutic candidates. Here, based on sequencing samples, phenotypes, profile RCD, developed an gene pair scoring system, named RCD.GP signature, showing reliable robust performance predicting prognosis glioblastoma. Using consisting Lasso, RSF, XgBoost, Enet, CoxBoost Boruta, identified seven genes as potential targets verified SLC43A3 expressed grades lines through qRT-PCR. Our study insights into roles glioma, signature patients, constructed core candidates oncogenic prediction biomarker

Language: Английский

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Upregulation of the ZNF148/PTX3 axis promotes malignant transformation of dendritic cells in glioma stem‐like cells microenvironment

CNS Neuroscience & Therapeutics, Journal Year: 2023, Volume and Issue: 29(9), P. 2690 - 2704

Published: April 17, 2023

Abstract Background The recent development of dendritic cell (DC)‐based immunotherapy has resulted in advances glioblastoma multiforme (GBM) treatment. However, the fate DCs GBM microenvironment, especially microenvironments which glioma stem (GSCs)‐mediated remodeling highly immunosuppressive conditions, not yet been fully investigated. Methods Observed interaction between GSCs and primary cultured a dual‐color tracing model, monoclonal continuously passaged proliferative DCs, named transformed (t‐DCs). expression DC‐specific surface markers was analyzed using RT‐PCR, chromosome karyotype, flow cytometry. long pentraxin 3 (PTX3) its transcription factor zinc finger protein 148 (ZNF148) t‐DCs detected qRT‐PCR western blot. CCK8 transwell assays were conducted to assess effect ZNF148 PTX3 on proliferation, migration, invasion t‐DCs. Bioinformatics analysis, dual‐luciferase reporter assay, chromatin immunoprecipitation (ChIP)‐qPCR assay used explore relation PTX3. Results Transformed (t‐DCs) still expressed markers, namely, CD80 CD11c, immune‐related costimulatory molecules, CD80, CD86, CD40, ICAM‐1. levels these molecules decreased moderately compared those naive DCs. Stable overexpression further promoted proliferation migration vitro, increased tumorigenicity vivo. directly bound promoter region enhanced expression. Downregulation significantly reduced Overexpression t‐DCs, achieving same biological effects as Simultaneously, downregulation partially reversed Conclusion ZNF148/PTX3 axis played an important role regulating malignant transformation after cross‐talk with GSCs, this may serve new target for sensitizing DC‐based immunotherapy.

Language: Английский

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An angiogenic proteome study of black raspberry extract on neuroendocrine cancers

Deleted Journal, Journal Year: 2025, Volume and Issue: unknown, P. 200198 - 200198

Published: Feb. 1, 2025

Language: Английский

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Pentraxin-3 as a Biomarker in Diabetes Mellitus: Insights into Inflammation, Vascular Complications, and Modulation by Antidiabetic Medications

Biomedicines, Journal Year: 2025, Volume and Issue: 13(4), P. 891 - 891

Published: April 7, 2025

Diabetes mellitus (DM) is a multifactorial metabolic disorder associated with systemic inflammation and vascular complications. Pentraxin-3 (PTX3) has emerged as key biomarker of endothelial dysfunction in DM. We aimed to examine the role PTX3 DM assesses impact pharmacological interventions on its expression. The review included studies analyzing modulation by antidiabetic therapies, such sodium-glucose cotransporter-2 inhibitors (SGLT-2i), glucagon-like peptide-1 agonists (GLP-1a), dipeptidyl peptidase-4 (DPP-4i), well effects lifestyle interventions. Clinical experimental demonstrated strong correlation between levels progression. Elevated were diabetic complications, including nephropathy, retinopathy, cardiovascular diseases. Antidiabetic drugs showed differential expression, GLP-1a DPP-4i significantly reducing levels, while SGLT-2i displayed paradoxical increase. Lifestyle interventions, dietary modifications weight loss, yielded inconsistent effects, suggesting genetic factors influence regulation. While particularly DPP-4i, demonstrate anti-inflammatory further research needed standardize measurement explore potential therapeutic target. Personalized treatment strategies incorporating profiling may optimize control disease management patients.

Language: Английский

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Electrochemical immunosensor based on poly(5-aminoindole) for cancer biomarker pentraxin-3 detection

Microchimica Acta, Journal Year: 2025, Volume and Issue: 192(5)

Published: April 25, 2025

Language: Английский

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Significance of serum APE1-AAbs, PTX-3, and miR-486-3p in patients with colorectal cancer undergoing radical surgery

World Journal of Gastrointestinal Oncology, Journal Year: 2025, Volume and Issue: 17(5)

Published: May 15, 2025

BACKGROUND Colorectal cancer (CRC) is a common malignant tumor of the digestive tract worldwide, characterized by high incidence and mortality rates. AIM To investigate expression serum apurinic/apyrimidinic endonuclease 1 autoantibodies (APE1-AAbs), peripheral pentraxin-3 (PTX-3), miR-486-3p in patients with CRC undergoing radical surgery their relationship postoperative recurrence metastasis. METHODS A retrospective analysis was conducted on clinical data 154 who underwent laparoscopic our hospital from January 2022 to 2024. Patients were followed for one year postoperatively divided into an occurrence group (n = 28) non-occurrence 126) based whether they experienced or The levels APE1-AAbs, PTX-3, compared between two groups. Multivariate logistic regression performed identify risk factors metastasis patients. analyzed using Spearman correlation analysis. Receiver operating characteristic curves drawn evaluate predictive value alone combination CRC. RESULTS had significantly higher proportions age ≥ 60 years, lymph node metastasis, stage III disease, poor differentiation, diameter > 5 cm, platelet count, carcinoembryonic antigen, carbohydrate antigen 19-9 than (P < 0.05). those showed that elevated (odds ratio 1, P revealed positively correlated (r 0.642, 0.653, 0.631, respectively, curve area under values predicting 0.764, 0.783, 0.806, 0.875, outperforming individual markers CONCLUSION Serum are These three can be used as biomarkers. combined detection these has tests.

Language: Английский

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The structural organisation of pentraxin-3 and its interactions with heavy chains of inter-α-inhibitor regulate crosslinking of the hyaluronan matrix

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 14, 2024

ABSTRACT Pentraxin-3 (PTX3) is an octameric protein, comprised of eight identical protomers, that has diverse functions in reproductive biology, innate immunity and cancer. PTX3 interacts with the large polysaccharide hyaluronan (HA) to which heavy chains (HCs) inter-α-inhibitor (IαI) family proteoglycans are covalently attached, playing a key role (non-covalent) crosslinking HC•HA complexes. These interactions stabilise cumulus matrix, essential for ovulation fertilisation mammals, also implicated formation pathogenic matrices context viral lung infections. To better understand physiological pathological roles we have analysed how its quaternary structure underpins HA via HCs. A combination X-ray crystallography, cryo-electron microscopy (cryo-EM) AlphaFold predictive modelling revealed C-terminal pentraxin domains octamer arranged central cube, two long extensions on either side, each formed from four protomers assembled into tetrameric coiled-coil regions, essentially as described by (Noone et al ., 2022; doi:10.1073/pnas.2208144119). From crystallography cryo-EM data, identified network inter-protomer salt bridges facilitate assembly octamer. Small angle scattering (SAXS) validated our model including analysis constructs: ‘Half-PTX3’ construct missing 24 N-terminal residues (Δ1-24-PTX3). SAXS determined length ∼520 Å and, combined 3D variability defined flexibility extensions. Biophysical analyses prototypical chain HC1 does not interact at pH 7.4, consistent previous studies showing that, this pH, only associates complexes if they presence. However, binds acidic can be incorporated pre-formed under these conditions. This provides novel mechanism regulation PTX3-mediated (e.g., during inflammation), likely mediated pH-dependent conformational change HC1. The was found associate simultaneously up molecules thus, potential form major node within matrices, i.e., where physical biochemical properties resulting could tuned HC/PTX3 composition.

Language: Английский

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Giant exophytic gastrointestinal stromal tumor (GIST) causing gastric outlet obstruction: case report and review of literature

Romanian Journal of Morphology and Embryology, Journal Year: 2024, Volume and Issue: 64(4), P. 595 - 601

Published: Jan. 4, 2024

Background: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors, mostly located within the stomach.About 30% of GISTs incidentally diagnosed and as they become symptomatic may be associated with bleeding, bowel obstruction or spontaneous rupture.Case presentation: We present case a middle-aged patient giant gastric GIST, which presented for intermittent outlet symptoms, emphasize major imagistic, histopathological, therapeutic challenges that encountered.There only several cases exophytic GIST provoking obstruction.Tumor resection should adapted to every patient's status, focused on en bloc extraction, preservation invaded organs much possible.

Language: Английский

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

Cancers, Journal Year: 2024, Volume and Issue: 16(9), P. 1637 - 1637

Published: April 24, 2024

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

Language: Английский

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