Neutrophil degranulation biomarkers characterize restrictive echocardiographic pattern with diastolic dysfunction in patients with diabetes

Ministrini, Stefano; Andreozzi, Francesco; Montecucco, Fabrizio; Minetti, Silvia; Bertolotto, Maria; Liberale, Luca; Mannino, Gaia Chiara; Succurro, Elena; Cassano, Velia; Miceli, Sofia; Perticone, Maria; Sesti, Giorgio; Sciacqua, Angela

doi:10.1111/eci.13640

Cited by 6 publications

(2 citation statements)

References 41 publications

(81 reference statements)

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“…MMP-9 (gelatinase B) is produced by immune cells (neutrophils, monocytes) and fibroblasts and plays a crucial role in ECM remodeling. We previously reported a significant increase in leukocyte MMP-2 expression in children/adolescents with essential hypertension [ 28 ], and up-regulation of MMP-2 expression has been found to be associated with the adipose tissue development [ 29 ]. We can speculate that increased serum MMP-9 observed in the obese children may originate from fat macrophages which display rather limited inflammatory phenotype further confirmed here by the low expression of the leukocyte MMP-2 , decreased MMP-2/TIMP-2 ratio, low TNF levels and negative correlations between leukocyte TIMP-2 expression and AST, ALT, and TGG plasma levels, as well as between leukocyte MMP-12 expression and GGTP plasma concentrations.…”

Section: Discussionmentioning

confidence: 99%

Implications of the Matrix Metalloproteinases, Their Tissue Inhibitors and Some Other Inflammatory Mediators Expression Levels in Children Obesity-Related Phenotypes

Wierzbicka-Rucińska,

Kubiszewska,

Grzywa-Czuba

et al. 2024

JPM

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Objectives: Matrix metalloproteinases (MMPs) are calcium-dependent zinc-containing endo-peptidases engaged in many biological processes including adipogenesis, angiogenesis, and tissue remodeling. Fat tissue infiltration by peripheral leukocytes plays an important role in transition of fat tissue residual, non-inflammatory status into the pro-inflammatory one, resulting in fat tissue inflammation and expansion as well as production of many mediators like adipokines and cytokines. The aim of this study was to investigate the expression of MMPs, their endogenous tissue inhibitors (TIMPs), and selected inflammatory mediators in leukocytes and plasma of children with simple obesity to find their associations with obesity-related phenotypes. Material and methods: Twenty-six overweight/obese children and twenty-three healthy volunteers participated in the study. The leukocyte mRNA expression levels of MMP-2, -9, -12 -14, TIMP-1, -2, and IL-6 were analyzed by the real time quantitative PCR. Plasma MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios as well as the concentrations of MMP-9, TIMP-1, IL-1 beta, IL-6, TNF- alpha, leptin and resistin were tested by ELISA assays. Gelatin zymography was used to assess the activity of the leukocyte MMPs proteins. Results: The obese children showed the following: a) increased expression of leukocyte TIMP-1 and slight elevation (close to statistical significance) of leukocyte MMP-9 (p = 0.054), the decline in MMP-2, b) elevation of plasma MMP-9, leptin, and MMP9/TIMP1 ratio, c) reduced expression of plasma TNF-alpha and MMP-2/TIMP-2 ratio. Several negative correlations were found: TIMP2 vs. ALT (r = −0.536), AST (r = −0.645) and TTG (r = −0.438), IL-6 vs. GGTP (r = −0.815), and MMP12 vs. TTG (r = −0.488), leptin vs. ALT (r = −0.569), MMP-9 vs. total cholesterol (r = −0.556). The only positive correlation was that of plasma leptin level vs. GGTP (r = 0.964). Conclusions: At the beginning of obesity development (children), possibly compensatory reactions prevail, reflected here by an increase in the expression of leukocyte MMPs inhibitor TIMP-1, decrease in the level of leukocyte MMP-2 and plasma MMP-2, MMP2/TIMP-2 ratio, low plasma TNF-alpha and negative correlations between the expression of TIMP-2 and liver (AST, ALT) or fat (TTG) inflammatory markers.

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Section: Discussionmentioning

confidence: 99%

Implications of the Matrix Metalloproteinases, Their Tissue Inhibitors and Some Other Inflammatory Mediators Expression Levels in Children Obesity-Related Phenotypes

Wierzbicka-Rucińska,

Kubiszewska,

Grzywa-Czuba

et al. 2024

JPM

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“…51 Neutrophil degranulation is related to an aberrant echocardiographic patterning T2D. 52 The expression of the FAS signaling pathway (CD95) was connected to systemic and skeletal muscle insulin resistance. 53 IFN-gamma or TNF-alpha Mediated Cell Proliferation is associated with T2D.…”

Section: Discussionmentioning

confidence: 99%

High throughput biological sequence analysis using machine learning-based integrative pipeline for extracting functional annotation and visualization

Al Amin,

Naznin,

Yeasmin

et al. 2024

F1000Res

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The Differential Gene Expression (DGE) approach to find out the expressed genes relies on measures such as log-fold change and adjusted p-values. Although fold change is commonly employed in gene expression studies, especially in microarray and RNA sequencing experiments to quantify alterations in a gene’s expression level, a limitation and potential hazard of relying on fold change in this context is its inherent bias. As a consequence, it might incorrectly categorize genes that have significant differences but minor ratios, resulting in poor detection of mutations in genes with high expression levels. In contrast, machine learning offers a more comprehensive view, adept at capturing the non-linear complexities of gene expression data and providing robustness against noise that inspired us to utilize machine learning models to explore differential gene expression based on feature importance in Type 2 Diabetes (T2D), a significant global health concern, in this study. Moreover, we validated biomarkers based on our findings expressed genes with previous studies to ensure the effectiveness of our ML models in this work which led us to go through to analysis pathways, gene ontologies, protein-protein interactions, transcription factors, miRNAs, and drug predictions to deal with T2D. This study aims to consider the machine learning technique as a good way to know about expressed genes profoundly not relying on the DGE approach, and to control or reduce the risk of T2D patients by helping drug developer researchers.

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Circulating Osteopontin Predicts Clinical and Radiological Response in First-Line Treatment of Advanced Non-Small Cell Lung Cancer

Ramoni,

Coco,

Rossi

et al. 2024

Lung

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Purpose Pembrolizumab-based regimens are conditioned by the expression of PD-L1, but durable response rate is limited by innate and acquired resistance mechanisms. Here, we focus on osteopontin (OPN), an upfront biomarker of senescence, which closely associated with natural history of non-small cell lung cancer (NSCLC). Methods Seventy-nine patients eligible to pembrolizumab regimens—alone or in combination with chemotherapy—as first-line treatment of advanced NSCLC were enrolled. Predictive value of OPN toward iRECIST progression disease (PD) was set as first outcome. Secondary ones included performance status (ECOG) at baseline, early (first and best) responses, and overall survival (OS). Results High Serum OPN characterized patients with worse ECOG-PS (p = 0.015) at baseline and subjects experienced PD/death at first (OR 1.17 [1.02 to 1.35]; p = 0.030) and best responses (0.04 [0.00 to 0.81]; p = 0.035). OPN was associated with time-to-progression (B -2.74 [−4.46 to −1.01]) and time-to death (−0.13 [−0.20 to −0.05]). Cox regression models unveil a predictive value for iRECIST-PD (HR 1.01 [1.00 to 1.02]; p = −0.005), RECIST-PD (HR 1.01 [1.00 to 1.02]; p = 0.017), and OS (HR 1.02 [1.01 to 1.03]; p = 0.001). These models were internally validated through bootstrap resampling and characterized by relevant discrimination ability at ROC curve analyses. Conclusion Baseline levels of serum OPN is closely associated with performance status and short/long term outcomes in patients with advanced NSCLC, which are candidate to pembrolizumab-based regimens. As upfront biomarker of senescence, OPN may pave the way for future studies focusing on senescence patterns in NSCLC.

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Neutrophil degranulation biomarkers characterize restrictive echocardiographic pattern with diastolic dysfunction in patients with diabetes

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 6 publications

References 41 publications

Implications of the Matrix Metalloproteinases, Their Tissue Inhibitors and Some Other Inflammatory Mediators Expression Levels in Children Obesity-Related Phenotypes

Implications of the Matrix Metalloproteinases, Their Tissue Inhibitors and Some Other Inflammatory Mediators Expression Levels in Children Obesity-Related Phenotypes

High throughput biological sequence analysis using machine learning-based integrative pipeline for extracting functional annotation and visualization

Circulating Osteopontin Predicts Clinical and Radiological Response in First-Line Treatment of Advanced Non-Small Cell Lung Cancer

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