Life | Special Issue : Emerging Biomarkers: Recent Findings and Its Application in Pathological Conditions Detection

Research

15 pages, 4751 KiB

Open AccessArticle

Human Amniotic Mesenchymal Stem Cells and Fibroblasts Accelerate Wound Repair of Cystic Fibrosis Epithelium

by Elisa Beccia, Valeria Daniello, Onofrio Laselva, Giorgia Leccese, Michele Mangiacotti, Sante Di Gioia, Gianfranco La Bella, Lorenzo Guerra, Maria Matteo, Antonella Angiolillo and Massimo Conese

Life 2022, 12(5), 756; https://doi.org/10.3390/life12050756 - 19 May 2022

Cited by 2 | Viewed by 1890

Abstract

Cystic fibrosis (CF) airways are affected by a deranged repair of the damaged epithelium resulting in altered regeneration and differentiation. Previously, we showed that human amniotic mesenchymal stem cells (hAMSCs) corrected base defects of CF airway epithelial cells via connexin (CX)43-intercellular gap junction [...] Read more.

Cystic fibrosis (CF) airways are affected by a deranged repair of the damaged epithelium resulting in altered regeneration and differentiation. Previously, we showed that human amniotic mesenchymal stem cells (hAMSCs) corrected base defects of CF airway epithelial cells via connexin (CX)43-intercellular gap junction formation. In this scenario, it is unknown whether hAMSCs, or fibroblasts sharing some common characteristics with MSCs, can operate a faster repair of a damaged airway epithelium. A tip-based scratch assay was employed to study wound repair in monolayers of CFBE14o- cells (CFBE, homozygous for the F508del mutation). hAMSCs were either co-cultured with CFBE cells before the wound or added to the wounded monolayers. NIH-3T3 fibroblasts (CX43+) were added to wounded cells. HeLa cells (CX43-) were used as controls. γ-irradiation was optimized to block CFBE cell proliferation. A specific siRNA was employed to downregulate CX43 expression in CFBE cells. CFBE cells showed a delayed repair as compared with wt-CFTR cells (16HBE41o-). hAMSCs enhanced the wound repair rate of wounded CFBE cell monolayers, especially when added post wounding. hAMSCs and NIH-3T3 fibroblasts, but not HeLa cells, increased wound closure of irradiated CFBE monolayers. CX43 downregulation accelerated CFBE wound repair rate without affecting cell proliferation. We conclude that hAMSCs and fibroblasts enhance the repair of a wounded CF airway epithelium, likely through a CX43-mediated mechanism mainly involving cell migration. Full article

(This article belongs to the Special Issue Emerging Biomarkers: Recent Findings and Its Application in Pathological Conditions Detection)

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17 pages, 3693 KiB

Open AccessArticle

LC-MS/MS-Based Serum Protein Profiling for Identification of Candidate Biomarkers in Pakistani Rheumatoid Arthritis Patients

by Sidrah Jahangir, Peter John, Attya Bhatti, Muhammad Muaaz Aslam, Javaid Mehmood Malik, James R. Anderson and Mandy J. Peffers

Life 2022, 12(3), 464; https://doi.org/10.3390/life12030464 - 21 Mar 2022

Cited by 2 | Viewed by 3179

Abstract

Rheumatoid arthritis is an autoimmune disorder of complex disease etiology. Currently available serological diagnostic markers lack in terms of sensitivity and specificity and thus additional biomarkers are warranted for early disease diagnosis and management. We aimed to screen and compare serum proteome profiles [...] Read more.

Rheumatoid arthritis is an autoimmune disorder of complex disease etiology. Currently available serological diagnostic markers lack in terms of sensitivity and specificity and thus additional biomarkers are warranted for early disease diagnosis and management. We aimed to screen and compare serum proteome profiles of rheumatoid arthritis serotypes with healthy controls in the Pakistani population for identification of potential disease biomarkers. Serum samples from rheumatoid arthritis patients and healthy controls were enriched for low abundance proteins using ProteoMiner^TM columns. Rheumatoid arthritis patients were assigned to one of the four serotypes based on anti-citrullinated peptide antibodies and rheumatoid factor. Serum protein profiles were analyzed via liquid chromatography-tandem mass spectrometry. The changes in the protein abundances were determined using label-free quantification software ProgenesisQI^TM followed by pathway analysis. Findings were validated in an independent cohort of patients and healthy controls using an enzyme-linked immunosorbent assay. A total of 213 proteins were identified. Comparative analysis of all groups (false discovery rate < 0.05, >2-fold change, and identified with ≥2 unique peptides) identified ten proteins that were differentially expressed between rheumatoid arthritis serotypes and healthy controls including pregnancy zone protein, selenoprotein P, C4b-binding protein beta chain, apolipoprotein M, N-acetylmuramoyl-L-alanine amidase, catalytic chain, oncoprotein-induced transcript 3 protein, Carboxypeptidase N subunit 2, Apolipoprotein C-I and Apolipoprotein C-III. Pathway analysis predicted inhibition of liver X receptor/retinoid X receptor activation pathway and production of nitric oxide and reactive oxygen species pathway in macrophages in all serotypes. A catalogue of potential serum biomarkers for rheumatoid arthritis were identified. These biomarkers can be further evaluated in larger cohorts from different populations for their diagnostic and prognostic potential. Full article

(This article belongs to the Special Issue Emerging Biomarkers: Recent Findings and Its Application in Pathological Conditions Detection)

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17 pages, 1354 KiB

Open AccessArticle

A Novel Paradigm Based on ST2 and Its Contribution towards a Multimarker Approach in the Diagnosis and Prognosis of Heart Failure: A Prospective Study during the Pandemic Storm

by Radu-Stefan Miftode, Daniela Constantinescu, Corina Maria Cianga, Antoniu Octavian Petris, Amalia-Stefana Timpau, Adrian Crisan, Irina-Iuliana Costache, Ovidiu Mitu, Dana-Teodora Anton-Paduraru, Ionela-Larisa Miftode, Mariana Pavel-Tanasa, Petru Cianga and Ionela-Lacramioara Serban

Life 2021, 11(10), 1080; https://doi.org/10.3390/life11101080 - 13 Oct 2021

Cited by 17 | Viewed by 2481

Abstract

Background: Acute heart failure (HF) represents an increasingly common and challenging presentation in the emergency room, also inducing a great socio-economic burden. Extensive research was conducted toward finding an ideal biomarker of acute HF, both in terms of sensitivity and specificity, but today [...] Read more.

Background: Acute heart failure (HF) represents an increasingly common and challenging presentation in the emergency room, also inducing a great socio-economic burden. Extensive research was conducted toward finding an ideal biomarker of acute HF, both in terms of sensitivity and specificity, but today practicians’ interest has shifted towards a more realistic multimarker approach. Natriuretic peptides (NPs) currently represent the gold standard for diagnosing HF in routine clinical practice, but novel molecules, such as sST2, emerge as potentially useful biomarkers, providing additional diagnostic and prognostic value. Methods: We conducted a prospective, single-center study that included 120 patients with acute HF and 53 controls with chronic HF. Of these, 13 patients (eight with acute HF, five from the control group) associated the coronavirus-19 disease (COVID-19). The diagnosis of HF was confirmed by a complete clinical, biological and echocardiographic approach. Results: The serum levels of all studied biomarkers (sST2, NT-proBNP, cardiac troponin) were significantly higher in the group with acute HF. By area under the curve (AUC) analysis, we noticed that NT-proBNP (AUC: 0.976) still had the best diagnostic performance, closely followed by sST2 (AUC: 0.889). However, sST2 was a significantly better predictor of fatal events, showing positive correlations for both in-hospital and at 1-month mortality rates. Moreover, sST2 was also associated with other markers of poor prognosis, such as the use of inotropes or high lactate levels, but not with left ventricle ejection fraction, age, body mass index or mean arterial pressure. sST2 levels were higher in patients with a positive history of COVID-19 as compared with non-COVID-19 patients, but the differences were statistically significant only within the control group. Bivariate regression showed a positive and linear relationship between NT-proBNP and sST2 (r(120) = 0.20, p < 0.002). Conclusions: we consider that sST2 has certain qualities worth integrating in a future multimarker test kit alongside traditional biomarkers, as it provides similar diagnostic value as NT-proBNP, but is emerging as a more valuable prognostic factor, with a better predictive value of fatal events in patients with acute HF. Full article

(This article belongs to the Special Issue Emerging Biomarkers: Recent Findings and Its Application in Pathological Conditions Detection)

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10 pages, 432 KiB

Open AccessArticle

High-Sensitivity C-Reactive Protein Relationship with Metabolic Disorders and Cardiovascular Diseases Risk Factors

by Małgorzata Koziarska-Rościszewska, Anna Gluba-Brzózka, Beata Franczyk and Jacek Rysz

Life 2021, 11(8), 742; https://doi.org/10.3390/life11080742 - 26 Jul 2021

Cited by 12 | Viewed by 2393

Abstract

Background. Chronic inflammation is considered to be involved in the development of CVD. It is important to find a simple test that enables the identification of patients at risk and that may be used in primary care. The aim of this study is [...] Read more.

Background. Chronic inflammation is considered to be involved in the development of CVD. It is important to find a simple test that enables the identification of patients at risk and that may be used in primary care. The aim of this study is to investigate the associations of high-sensitivity C-reactive protein (hsCRP) with selected factors—age, gender, obesity, dyslipidemia, diabetes, hyperuricemia, vitamin D-25(OH)D, cardiovascular diseases (CVD), coronary heart disease, cerebrovascular disease, and hypertension. Results. Statistically significant correlations were found between hsCRP and the following: age (rs = 0.304, p = 0.0000); gender (female) (p = 0.0173); BMI (rs = 0.295, p = 0.0001); waist circumference (rs = 0.250, p = 0.0007); dyslipidemia (p = 0.0159); glycemia (rs = 0.173, p = 0.0207); and significant negative correlations between hsCRP and 25(OH)D (rs = −0.203, p = 0.0065). In patients with CVD, hypertension, diabetes, or visceral obesity, hsCRP was significantly higher than in the subgroup without these disorders. There was a statistically significant relationship between hsCRP and the number of the metabolic syndrome elements (p = 0.0053). Conclusions. The hsCRP test seem to be a simple test that may be used at the primary care level to identify patients at risk of metabolic disorders, CVD, and hypertension. Vitamin D concentration may be a determining factor of systemic inflammation (it may have a modulating effect). Full article

(This article belongs to the Special Issue Emerging Biomarkers: Recent Findings and Its Application in Pathological Conditions Detection)

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13 pages, 3619 KiB

Open AccessArticle

Expression Status and Prognostic Value of m⁶A RNA Methylation Regulators in Lung Adenocarcinoma

by Xiuhong Li, Zian Feng, Rui Wang, Jie Hu, Xiaodong He and Zuojun Shen

Life 2021, 11(7), 619; https://doi.org/10.3390/life11070619 - 26 Jun 2021

Cited by 4 | Viewed by 1894

Abstract

N⁶-methyladenosine (m⁶A) RNA modification is the most abundant modification method in mRNA, and it plays an important role in the occurrence and development of many cancers. This paper mainly discusses the role of m⁶A RNA methylation regulators [...] Read more.

N⁶-methyladenosine (m⁶A) RNA modification is the most abundant modification method in mRNA, and it plays an important role in the occurrence and development of many cancers. This paper mainly discusses the role of m⁶A RNA methylation regulators in lung adenocarcinoma (LUAD) to identify novel prognostic biomarkers. The gene expression data of 19 m⁶A methylation regulators in LUAD patients and its relevant clinical parameters were extracted from The Cancer Genome Atlas (TCGA) database. We selected three significantly differentially expressed m⁶A regulators in LUAD to construct the risk signature, and evaluated its prognostic prediction efficiency using the receiver operating characteristic (ROC) curve. Kaplan–Meier survival analysis and Cox regression analysis were used to identify the independent prognostic significance of the risk signature. The ROC curve indicated that the area under the curve (AUC) was 0.659, which means that the risk signature had a good prediction efficiency. The results of the Kaplan–Meier survival analysis and Cox regression analysis showed that the risk score can be used as an independent prognostic factor for LUAD. In addition, we explored the differential signaling pathways and cellular processes related to m⁶A methylation regulators in LUAD. Full article

(This article belongs to the Special Issue Emerging Biomarkers: Recent Findings and Its Application in Pathological Conditions Detection)

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15 pages, 1675 KiB

Open AccessEditor’s ChoiceArticle

CEACAM6’s Role as a Chemoresistance and Prognostic Biomarker for Pancreatic Cancer: A Comparison of CEACAM6’s Diagnostic and Prognostic Capabilities with Those of CA19-9 and CEA

by Benediktas Kurlinkus, Marija Ger, Algirdas Kaupinis, Eugenijus Jasiunas, Mindaugas Valius and Audrius Sileikis

Life 2021, 11(6), 542; https://doi.org/10.3390/life11060542 - 9 Jun 2021

Cited by 7 | Viewed by 2482

Abstract

Survival rates from pancreatic cancer have remained stagnant for decades due to the heterogenic nature of the disease. This study aimed to find a new advanced biomarker and evaluate its clinical capabilities, thus enabling more individualised pancreatic cancer management. Between 2013 and 2020, [...] Read more.

Survival rates from pancreatic cancer have remained stagnant for decades due to the heterogenic nature of the disease. This study aimed to find a new advanced biomarker and evaluate its clinical capabilities, thus enabling more individualised pancreatic cancer management. Between 2013 and 2020, 267 patients were included in the study. Surgically collected pancreatic tissue samples were analysed via high-definition mass spectrometry. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) was discovered as a possible promising pancreatic cancer biomarker. The predominance of CEACAM6 to pancreatic cancer was validated using antibodies in tissue samples. CEACAM6, carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA) blood serum concentrations were evaluated for clinical evaluation and comparison. Kaplan–Meier survival analyses were used to evaluate disease-free survival (DFS) and overall survival (OS). Poorer overall survival was significantly dependent on increased CEACAM6 blood serum concentrations (17.0 vs. 12.6 months, p = 0.017) in pancreatic cancer patients after radical treatment and adjuvant chemotherapy. Increased CEA and CA19-9 concentrations showed no significant dependencies with survival. Thus, CEACAM6 is a promising new biomarker with significant prognostic value and prediction of chemoresistance properties, enabling the improvement of individualised approaches to patients with pancreatic cancer. Full article

(This article belongs to the Special Issue Emerging Biomarkers: Recent Findings and Its Application in Pathological Conditions Detection)

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10 pages, 796 KiB

Open AccessArticle

Altered Blood Levels of Anti-Gal Antibodies in Alzheimer’s Disease: A New Clue to Pathogenesis?

by Antonella Angiolillo, Alessandro Gandaglia, Alessia Arcaro, Andrea Carpi, Fabrizio Gentile, Filippo Naso and Alfonso Di Costanzo

Life 2021, 11(6), 538; https://doi.org/10.3390/life11060538 - 9 Jun 2021

Cited by 6 | Viewed by 2406

Abstract

Alzheimer’s disease is a neurodegenerative disorder whose pathological mechanisms, despite recent advances, are not fully understood. However, the deposition of beta amyloid -peptide and neuroinflammation, which is probably aggravated by dysbiotic microbiota, seem to play a key role. Anti-Gal are the most abundant [...] Read more.

Alzheimer’s disease is a neurodegenerative disorder whose pathological mechanisms, despite recent advances, are not fully understood. However, the deposition of beta amyloid -peptide and neuroinflammation, which is probably aggravated by dysbiotic microbiota, seem to play a key role. Anti-Gal are the most abundant xenoreactive natural antibodies. They are supposed to stem from immunization against the gut microbiota and have been implicated in the pathogenesis of several diseases, including multiple sclerosis. These antibodies target the alpha-Gal epitope, expressed on the terminal sugar units of glycoprotein or glycolipid of all mammals except apes, Old World monkeys and humans. The alpha-Gal is constitutively expressed in several bacteria constituting the brain microbiota, and alpha-Gal-like epitopes have been detected in gray matter, amyloid plaque, neurofibrillary tangles and corpora amylacea of the human brain, suggesting a potential link between anti-Gal and Alzheimer’s disease etiopathogenesis. For the first time, our study searched for possible alterations of anti-Gal immunoglobulin levels in Alzheimer’s disease patients. IgG and IgM blood levels were significantly lower, and IgA significantly higher in patients than in healthy subjects. These results suggest that such immunoglobulins might be implicated in Alzheimer’s disease pathogenesis and open new scenarios in the research for new biomarkers and therapeutic strategies. Full article

(This article belongs to the Special Issue Emerging Biomarkers: Recent Findings and Its Application in Pathological Conditions Detection)

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14 pages, 1123 KiB

Open AccessArticle

Association of SDF1 and MMP12 with Atherosclerosis and Inflammation: Clinical and Experimental Study

by María Marcos-Jubilar, Josune Orbe, Carmen Roncal, Florencio J. D. Machado, José Antonio Rodriguez, Alejandro Fernández-Montero, Inmaculada Colina, Raquel Rodil, Juan C. Pastrana and José A. Páramo

Life 2021, 11(5), 414; https://doi.org/10.3390/life11050414 - 1 May 2021

Cited by 8 | Viewed by 2174

Abstract

BACKGROUND: Atherosclerosis is the main etiology of cardiovascular diseases (CVD), associated to systemic inflammation. Matrix metalloproteinases (MMPs) are related to atherosclerosis progression through the SDF1/CXCR4 axis promoting macrophages recruitment within the vascular wall. The goal was to assess new circulatory inflammatory markers in [...] Read more.

BACKGROUND: Atherosclerosis is the main etiology of cardiovascular diseases (CVD), associated to systemic inflammation. Matrix metalloproteinases (MMPs) are related to atherosclerosis progression through the SDF1/CXCR4 axis promoting macrophages recruitment within the vascular wall. The goal was to assess new circulatory inflammatory markers in relation to atherosclerosis. METHODS: Measurement of SDF1, MMP12 and CRP in blood samples of 298 prospective patients with cardiovascular risk. To explore atherosclerosis progression, CXCR4/SDF1 axis and MMP12 expression were determined by RT-qPCR and by immunohistochemistry in the aorta of accelerated and delayed atherosclerosis mice models (Apoe-/- and Apoe-/-Mmp10-/-). RESULTS: SDF1, MMP12 and CRP were elevated in patients with clinical atherosclerosis, but after controlling by confounding factors, only SDF1 and CRP remained increased. Having high levels of both biomarkers showed 2.8-fold increased risk of presenting clinical atherosclerosis (p = 0.022). Patients with elevated SDF1, MMP12 and CRP showed increased risk of death in follow-up (HR = 3.2, 95%CI: 1.5–7.0, p = 0.004). Gene and protein expression of CXCR4 and MMP12 were increased in aortas from Apoe-/- mice. CONCLUSIONS: The combination of high circulating SDF1, MMP12 and CRP identified patients with particular inflammatory cardiovascular risk and increased mortality. SDF1/CXCR4 axis and MMP12 involvement in atherosclerosis development suggests that they could be possible atherosclerotic targets. Full article

(This article belongs to the Special Issue Emerging Biomarkers: Recent Findings and Its Application in Pathological Conditions Detection)

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