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Keywords = procollagen type I C-terminal propeptide (PICP)

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22 pages, 307 KiB  
Article
The Long-Term Impact of Preterm Birth on Metabolic Bone Profile and Bone Mineral Density in Childhood
by Panagiota Markopoulou, Artemis Doulgeraki, Arsinoi Koutroumpa, Georgios Polyzois, Helen Athanasopoulou, Christina Kanaka-Gantenbein and Tania Siahanidou
Metabolites 2025, 15(7), 463; https://doi.org/10.3390/metabo15070463 - 8 Jul 2025
Viewed by 397
Abstract
Background/Objectives: Recent data on long-term consequences of prematurity on bone health are conflicting. The aim of this study was to assess the metabolic bone profile and bone mineral density (BMD) in prepubertal children born prematurely and to examine possible associations between bone [...] Read more.
Background/Objectives: Recent data on long-term consequences of prematurity on bone health are conflicting. The aim of this study was to assess the metabolic bone profile and bone mineral density (BMD) in prepubertal children born prematurely and to examine possible associations between bone health parameters and perinatal morbidity factors. Methods: This cross-sectional observational study included 144 children of mean (SD) age 10.9 (1.6) years: 49 children born very preterm (≤32 gestational weeks), 37 moderate-to-late preterm (32+1 to 36+6 gestational weeks), and 58 born at term (controls). Serum levels of calcium/Ca, phosphorus/P, alkaline phosphatase/ALP, 25-hydroxyvitamin D/25(OH)D, bone formation markers (osteocalcin/OC, procollagen type I C-terminal propeptide/PICP, and insulin growth factor-1/IGF-1), and bone resorption markers (serum tartrate-resistant acid phosphatase 5b/bone TRAP5band urinary calcium-to-creatinine ratio) were measured. Total-body and lumbar-spine BMD and BMD Z-scores were calculated using dual-energy X-ray absorptiometry/DXA. Results: Children born very preterm showed significantly higher ALP, OC, PICP, and bone TRAP5b levels compared to controls, as well as compared to children born moderate-to-late preterm. Total-body and lumbar-spine BMD Z-scores were significantly lower in the very preterm-born group compared to controls. Gestational diabetes, preeclampsia, and bronchopulmonary dysplasia were associated with lower total-body BMD in the very preterm-born population. Conclusions: Preterm birth is associated with impaired metabolic bone profile and lower total-body and lumbar-spine BMD in childhood. Moderate-to-late preterm-born children exhibit altered metabolic bone parameters compared to very preterm-born children. Further research in children might allow better insight into the long-term impact of preterm birth on bone health. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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16 pages, 1361 KiB  
Article
Effect of an Intensive Lifestyle Intervention on Circulating Biomarkers of Atrial Fibrillation-Related Pathways among Adults with Metabolic Syndrome: Results from a Randomized Trial
by Linzi Li, Alvaro Alonso, Dora Romaguera, Angel M. Alonso-Gómez, Cristina Razquin, Lucas Tojal-Sierra, Miquel Fiol, Miguel Angel Martínez-González, Vinita Subramanya, Jordi Salas-Salvadó, Montserrat Fito and Estefanía Toledo
J. Clin. Med. 2024, 13(7), 2132; https://doi.org/10.3390/jcm13072132 - 7 Apr 2024
Cited by 2 | Viewed by 2132
Abstract
Background: Lifestyles influence atrial fibrillation (AF) risk. Determining the effect of lifestyle interventions on blood concentrations of biomarkers of AF-related pathways could help understand AF pathophysiology and contribute to AF prevention. Methods: We studied 532 participants enrolled in the PREDIMED-Plus trial, [...] Read more.
Background: Lifestyles influence atrial fibrillation (AF) risk. Determining the effect of lifestyle interventions on blood concentrations of biomarkers of AF-related pathways could help understand AF pathophysiology and contribute to AF prevention. Methods: We studied 532 participants enrolled in the PREDIMED-Plus trial, a Spanish randomized trial conducted in adults (55–75 years) with metabolic syndrome and body mass index between 27–40 kg/m2. Eligible participants were randomized 1:1 to an intensive lifestyle intervention, emphasizing physical activity, weight loss, and adherence to an energy-reduced Mediterranean diet or to a control group. Serum biomarkers [carboxy-terminal propeptide of procollagen type I (PICP), high-sensitivity troponin T (hsTnT), high-sensitivity C reactive protein (hsCRP), 3-nitrotyrosine (3-NT), and N-terminal propeptide of B-type natriuretic peptide (NT-proBNP)] were measured at baseline, 3 and 5 years after randomization. Mixed models were used to evaluate the effect of intervention on changes in biomarkers through year 5. Mediation analysis was performed to examine the proportion mediated by each component of the intervention. Results: At baseline, participants’ mean age was 65, 40% were female, and 50% were assigned to the intervention. After five years, mean changes in log-transformed biomarkers were −0.01 (PICP), 0.20 (hsTnT), −0.17 (hsCRP), 0.12 (3-NT), and 0.27 (NT-proBNP). Compared to the control group, participants in the intervention group experienced greater decreases in hsCRP (−14%, 95% confidence interval (CI) −26%, 0%) or smaller increases in 3-NT (−16%, 95% CI −25%, −5%) and NT-proBNP (−12%, 95% CI −23%, 1%). The intervention had minimal impact on hsTnT (−3%, 95% CI −7%, 2%) or PICP concentrations (−2%, 95% CI −9%, 6%). The effect of the intervention on hsCRP was primarily mediated by weight loss (89% at year 5). Conclusions: Over five years, a dietary and lifestyle intervention for weight-loss favorably affected concentrations of hsCRP, 3-NT, and NT-proBNP, pointing to specific mechanisms in pathways linking lifestyles and AF. Full article
(This article belongs to the Section Epidemiology & Public Health)
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47 pages, 2234 KiB  
Review
Revisiting Circulating Extracellular Matrix Fragments as Disease Markers in Myelofibrosis and Related Neoplasms
by Hans Carl Hasselbalch, Peter Junker, Vibe Skov, Lasse Kjær, Trine A. Knudsen, Morten Kranker Larsen, Morten Orebo Holmström, Mads Hald Andersen, Christina Jensen, Morten A. Karsdal and Nicholas Willumsen
Cancers 2023, 15(17), 4323; https://doi.org/10.3390/cancers15174323 - 29 Aug 2023
Cited by 5 | Viewed by 4292
Abstract
Philadelphia chromosome-negative chronic myeloproliferative neoplasms (MPNs) arise due to acquired somatic driver mutations in stem cells and develop over 10–30 years from the earliest cancer stages (essential thrombocythemia, polycythemia vera) towards the advanced myelofibrosis stage with bone marrow failure. The JAK2V617F mutation is [...] Read more.
Philadelphia chromosome-negative chronic myeloproliferative neoplasms (MPNs) arise due to acquired somatic driver mutations in stem cells and develop over 10–30 years from the earliest cancer stages (essential thrombocythemia, polycythemia vera) towards the advanced myelofibrosis stage with bone marrow failure. The JAK2V617F mutation is the most prevalent driver mutation. Chronic inflammation is considered to be a major pathogenetic player, both as a trigger of MPN development and as a driver of disease progression. Chronic inflammation in MPNs is characterized by persistent connective tissue remodeling, which leads to organ dysfunction and ultimately, organ failure, due to excessive accumulation of extracellular matrix (ECM). Considering that MPNs are acquired clonal stem cell diseases developing in an inflammatory microenvironment in which the hematopoietic cell populations are progressively replaced by stromal proliferation—“a wound that never heals”—we herein aim to provide a comprehensive review of previous promising research in the field of circulating ECM fragments in the diagnosis, treatment and monitoring of MPNs. We address the rationales and highlight new perspectives for the use of circulating ECM protein fragments as biologically plausible, noninvasive disease markers in the management of MPNs. Full article
(This article belongs to the Topic Biomarker Development and Application)
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20 pages, 401 KiB  
Review
Biomarkers for Prostate Cancer Bone Metastasis Detection and Prediction
by Mingshuai Ying, Jianshui Mao, Lingchao Sheng, Hongwei Wu, Guangchao Bai, Zhuolin Zhong and Zhijun Pan
J. Pers. Med. 2023, 13(5), 705; https://doi.org/10.3390/jpm13050705 - 22 Apr 2023
Cited by 13 | Viewed by 4868
Abstract
Prostate cancer (PCa) causes deaths worldwide, ranking second after lung cancer. Bone metastasis (BM) frequently results from advanced PCa, affecting approximately 90% of patients, and it also often results in severe skeletal-related events. Traditional diagnostic methods for bone metastases, such as tissue biopsies [...] Read more.
Prostate cancer (PCa) causes deaths worldwide, ranking second after lung cancer. Bone metastasis (BM) frequently results from advanced PCa, affecting approximately 90% of patients, and it also often results in severe skeletal-related events. Traditional diagnostic methods for bone metastases, such as tissue biopsies and imaging, have substantial drawbacks. This article summarizes the significance of biomarkers in PCa accompanied with BM, including (1) bone formation markers like osteopontin (OPN), pro-collagen type I C-terminal pro-peptide (PICP), osteoprotegerin (OPG), pro-collagen type I N-terminal pro-peptide (PINP), alkaline phosphatase (ALP), and osteocalcin (OC); (2) bone resorption markers, including C-telopeptide of type I collagen (CTx), N-telopeptide of type I collagen (NTx), bone sialoprotein (BSP), tartrate-resistant acid phosphatase (TRACP), deoxypyridinoline (D-PYD), pyridoxine (PYD), and C-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP); (3) prostate-specific antigen (PSA); (4) neuroendocrine markers, such as chromogranin A (CgA), neuron-specific enolase (NSE), and pro-gastrin releasing peptide (ProGRP); (5) liquid biopsy markers, such as circulating tumor cells (CTCs), microRNA (miRNA), circulating tumor DNA (ctDNA), and cell-free DNA (cfDNA) and exosomes. In summary, some of these markers are already in widespread clinical use, while others still require further laboratory or clinical studies to validate their value for clinical application. Full article
21 pages, 1616 KiB  
Article
A Fibrosis Biomarker Early Predicts Cardiotoxicity Due to Anthracycline-Based Breast Cancer Chemotherapy
by Ana de la Fuente, Marta Santisteban, Josep Lupón, José Manuel Aramendía, Agnes Díaz, Ana Santaballa, Amparo Hernándiz, Pilar Sepúlveda, Germán Cediel, Begoña López, José María López Picazo, Manuel M. Mazo, Gregorio Rábago, Juan José Gavira, Ignacio García-Bolao, Javier Díez, Arantxa González, Antoni Bayés-Genís and Susana Ravassa
Cancers 2022, 14(12), 2941; https://doi.org/10.3390/cancers14122941 - 14 Jun 2022
Cited by 5 | Viewed by 2823
Abstract
Anthracycline-based cancer chemotherapy (ACC) causes myocardial fibrosis, a lesion contributing to left ventricular dysfunction (LVD). We investigated whether the procollagen-derived type-I C-terminal-propeptide (PICP): (1) associates with subclinical LVD (sLVD) at 3-months after ACC (3m-post-ACC); (2) predicts cardiotoxicity 1-year after ACC (12m-post-ACC) in breast [...] Read more.
Anthracycline-based cancer chemotherapy (ACC) causes myocardial fibrosis, a lesion contributing to left ventricular dysfunction (LVD). We investigated whether the procollagen-derived type-I C-terminal-propeptide (PICP): (1) associates with subclinical LVD (sLVD) at 3-months after ACC (3m-post-ACC); (2) predicts cardiotoxicity 1-year after ACC (12m-post-ACC) in breast cancer patients (BC-patients); and (3) associates with LVD in ACC-induced heart failure patients (ACC-HF-patients). Echocardiography, serum PICP and biomarkers of cardiomyocyte damage were assessed in two independent cohorts of BC-patients: CUN (n = 87) at baseline, post-ACC, and 3m and 12m (n = 65)-post-ACC; and HULAFE (n = 70) at baseline, 3m and 12m-post-ACC. Thirty-seven ACC-HF-patients were also studied. Global longitudinal strain (GLS)-based sLVD (3m-post-ACC) and LV ejection fraction (LVEF)-based cardiotoxicity (12m-post-ACC) were defined according to guidelines. BC-patients: all biomarkers increased at 3m-post-ACC versus baseline. PICP was particularly increased in patients with sLVD (interaction-p < 0.001) and was associated with GLS (p < 0.001). PICP increase at 3m-post-ACC predicted cardiotoxicity at 12m-post-ACC (odds-ratio ≥ 2.95 per doubling PICP, p ≤ 0.025) in both BC-cohorts, adding prognostic value to the early assessment of GLS and LVEF. ACC-HF-patients: PICP was inversely associated with LVEF (p = 0.004). In ACC-treated BC-patients, an early increase in PICP is associated with early sLVD and predicts cardiotoxicity 1 year after ACC. PICP is also associated with LVD in ACC-HF-patients. Full article
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10 pages, 1595 KiB  
Article
Impact of Immunosuppressive Drugs on Fibroblasts: An In Vitro Study
by Gunar Wagner, Lisa Sievers, Malte Tiburcy, Wolfram Hubertus Zimmermann, Otto Kollmar, Gerhard Schmalz and Dirk Ziebolz
J. Clin. Med. 2022, 11(11), 3107; https://doi.org/10.3390/jcm11113107 - 31 May 2022
Cited by 2 | Viewed by 1999
Abstract
Background: The aim of this study was to compare the direct impact of different agents for immunosuppressive therapy on mouse fibroblasts as a possible cause of drug-induced gingival overgrowth (DIGO). Methods: 3T3 mouse fibroblasts were cultivated in cell-specific media (2 × 104 [...] Read more.
Background: The aim of this study was to compare the direct impact of different agents for immunosuppressive therapy on mouse fibroblasts as a possible cause of drug-induced gingival overgrowth (DIGO). Methods: 3T3 mouse fibroblasts were cultivated in cell-specific media (2 × 104 cells/mL) and treated for 6, 24, 48 and 72 h with one of three immunosuppressive drugs (IsDs): cyclosporin a (CsA), tacrolimus (TaC) and sirolimus (SiR). Different concentrations (10–750 ng/mL) were used to mimic serum levels under active immunosuppressive therapy conditions. Cell population characteristics (cell number, viability and morphology) were assessed using computer-assisted cell analysis. Expression of pro-collagen type I carboxy-terminal propeptide (PICP) was identified using an ELISA assay. Results: The influence of IsDs on the biological status of 3T3 fibroblasts was time- and dose-dependent. Comparing CsA and TaC, the total cell amount was enhanced using concentrations in the range of 10–150 ng/mL (p > 0.05). In contrast, treatment with SiR resulted in a decrease in the average cell number (p < 0.01). PICP and cell diameter of fibroblasts were not susceptible to IsD treatment (p > 0.05). Conclusions: Our results revealed time-dependent effects of IsDs, with distinct influences on cell number. The cell morphology and the PICP balance of the investigated fibroblast cell line remained unaffected. Hence, the potential role of IsDs is not a unilateral mechanism of action but rather a multifactorial process. Full article
(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)
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19 pages, 2704 KiB  
Article
Bone Metabolism and RANKL/OPG Ratio in Rheumatoid Arthritis Women Treated with TNF-α Inhibitors
by Agnieszka Jura-Półtorak, Anna Szeremeta, Krystyna Olczyk, Aleksandra Zoń-Giebel and Katarzyna Komosińska-Vassev
J. Clin. Med. 2021, 10(13), 2905; https://doi.org/10.3390/jcm10132905 - 29 Jun 2021
Cited by 39 | Viewed by 3747
Abstract
The aim of this study was to evaluate the effect of anti-tumor necrosis factor α (anti-TNF-α) therapy in combination with methotrexate on bone remodeling and osteoclastogenesis in female patients with RA. Serum levels of bone turnover markers (i.e., C- and N-terminal propeptides of [...] Read more.
The aim of this study was to evaluate the effect of anti-tumor necrosis factor α (anti-TNF-α) therapy in combination with methotrexate on bone remodeling and osteoclastogenesis in female patients with RA. Serum levels of bone turnover markers (i.e., C- and N-terminal propeptides of type I procollagen (PICP and PINP), C- and N-terminal cross-linking telopeptides of type I collagen (CTX-I and NTX-I), and soluble receptor activator of nuclear factor κB ligand (sRANKL) and osteoprotegerin (OPG)) were determined by immunoassay at baseline and 15 months after initiation of treatment. Bone mineral density was measured by dual-energy x-ray absorptiometry. We found a significant decrease in serum PINP levels, a biomarker of bone formation, and higher levels of CTX-I and sRANKL indicative of increased bone resorption in RA patients prior to TNFαI treatment compared to the controls. Anti-TNF-α therapy was effective in improving bone metabolism in RA patients as reflected in a decrease in CTX-I (at least partially due to the RANKL/OPG reduction) and a concomitant increase in PINP levels. The bone metabolism changes were independent of the type of TNFαI used. PINP and CTX-I were found to be useful markers of bone metabolism, which may prove the effectiveness of TNF-α therapy earlier than the bone density assessment. Full article
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