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  • 1
    Online Resource
    Online Resource
    Proliferation Pattern of Pediatric Tumor-Derived Mesenchymal Stromal Cells and Role in Cancer Dormancy: A Perspective of Study for Surgical Strategy
    Frontiers Media SA ; 2021
    In:  Frontiers in Pediatrics Vol. 9 ( 2021-11-4)
    Details
    In: Frontiers in Pediatrics, Frontiers Media SA, Vol. 9 ( 2021-11-4)
    Abstract: The explanation for cancer recurrence still remains to be fully elucidated. Moreover, tumor dormancy, which is a process whereby cells enter reversible G 0 cell cycle arrest, appears to be a critical step in this phenomenon. We evaluated the cell cycle proliferation pattern in pediatric tumor-derived mesenchymal stromal cells (MSCs), in order to provide a better understanding of the complex mechanisms underlying cancer dormancy. Specimens were obtained from 14 pediatric patients diagnosed with solid tumors and submitted to surgery. Morphology, phenotype, differentiation, immunological capacity, and proliferative growth of tumor MSCs were studied. Flow cytometric analysis was performed to evaluate the cell percentage of each cell cycle phase. Healthy donor bone marrow-derived mesenchymal stromal cells (BM-MSCs) were employed as controls. It was noted that the DNA profile of proliferating BM-MSC was different from that of tumor MSCs. All BM-MSCs expressed the typical DNA profile of proliferating cells, while in all tumor MSC samples, ≥70% of the cells were detected in the G0/G1 phase. In particular, seven tumor MSC samples displayed intermediate cell cycle behavior, and the other seven tumor MSC samples exhibited a slow cell cycle. The increased number of tumor MSCs in the G0–G1 phase compared with BM-MSCs supports a role for quiescent MSCs in tumor dormancy regulation. Understanding the mechanisms that promote dormant cell cycle arrest is essential in identifying predictive markers of recurrence and to promote a dedicated surgical planning.
    Type of Medium: Online Resource
    ISSN: 2296-2360
    URL: Article
    DOI: 10.3389/fped.2021.766610
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2711999-3
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  • 2
    Online Resource
    Online Resource
    The Role of Hypoxia in Improving the Therapeutic Potential of Mesenchymal Stromal Cells. A Comparative Study From Healthy Lung and Congenital Pulmonary Airway Malformations in Infants
    Frontiers Media SA ; 2022
    In:  Frontiers in Bioengineering and Biotechnology Vol. 10 ( 2022-6-14)
    Details
    In: Frontiers in Bioengineering and Biotechnology, Frontiers Media SA, Vol. 10 ( 2022-6-14)
    Abstract: Mesenchymal stromal cells (MSCs) play an important role in the field of regenerative medicine thanks to their immunomodulatory properties and their ability to secrete paracrine factors. The use of MSCs has also been tested in children with congenital lung diseases inducing fibrosis and a decrease in lung function. Congenital malformations of the pulmonary airways (CPAM) are the most frequently encountered lung lesion that results from defects in early development of airways. Despite the beneficial properties of MSCs, interventions aimed at improving the outcome of cell therapy are needed. Hypoxia may be an approach aimed to ameliorate the therapeutic potential of MSCs. In this regard, we evaluated the transcriptomic profile of MSCs collected from pediatric patients with CPAM, analyzing similarities and differences between healthy tissue (MSCs-lung) and cystic tissue (MSCs-CPAM) both in normoxia and in cells preconditioned with hypoxia (0.2%) for 24 h. Study results showed that hypoxia induces cell cycle activation, increasing in such a way the cell proliferation ability, and enhancing cell anaerobic metabolism in both MSCs-lung and MSCs-CPAM-lung. Additionally, hypoxia downregulated several pro-apoptotic genes preserving MSCs from apoptosis and, at the same time, improving their viability in both comparisons. Finally, data obtained indicates that hypoxia leads to a greater expression of genes involved in the regulation of the cytoskeleton in MSCs-lung than MSCs-CPAM.
    Type of Medium: Online Resource
    ISSN: 2296-4185
    URL: Article
    DOI: 10.3389/fbioe.2022.868486
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2719493-0
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  • 3
    Online Resource
    Online Resource
    Prenatal Hypoxia and Placental Oxidative Stress: Insights from Animal Models to Clinical Evidences
    MDPI AG ; 2020
    In:  Antioxidants Vol. 9, No. 5 ( 2020-05-12), p. 414-
    Details
    In: Antioxidants, MDPI AG, Vol. 9, No. 5 ( 2020-05-12), p. 414-
    Abstract: Hypoxia is a common form of intrauterine stress characterized by exposure to low oxygen concentrations. Gestational hypoxia is associated with the generation of reactive oxygen species. Increase in oxidative stress is responsible for damage to proteins, lipids and DNA with consequent impairment of normal cellular functions. The purpose of this review is to propose a summary of preclinical and clinical evidences designed to outline the correlation between fetal hypoxia and oxidative stress. The results of the studies described show that increases of oxidative stress in the placenta is responsible for changes in fetal development. Specifically, oxidative stress plays a key role in vascular, cardiac and neurological disease and reproductive function dysfunctions. Moreover, the different finding suggests that the prenatal hypoxia-induced oxidative stress is associated with pregnancy complications, responsible for changes in fetal programming. In this way, fetal hypoxia predisposes the offspring to congenital anomalies and chronic diseases in future life. Several antioxidant agents, such as melatonin, erythropoietin, vitamin C, resveratrol and hydrogen, shown potential protective effects in prenatal hypoxia. However, future investigations will be needed to allow the implementation of these antioxidants in clinical practice for the promotion of health in early intrauterine life, in fetuses and children.
    Type of Medium: Online Resource
    ISSN: 2076-3921
    URL: Article
    DOI: 10.3390/antiox9050414
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2704216-9
    SSG: 15,3
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  • 4
    Online Resource
    Online Resource
    Transcriptomic Analysis of HCN-2 Cells Suggests Connection among Oxidative Stress, Senescence, and Neuron Death after SARS-CoV-2 Infection
    MDPI AG ; 2021
    In:  Cells Vol. 10, No. 9 ( 2021-08-25), p. 2189-
    Details
    In: Cells, MDPI AG, Vol. 10, No. 9 ( 2021-08-25), p. 2189-
    Abstract: According to the neurological symptoms of SARS-CoV-2 infection, it is known that the nervous system is influenced by the virus. We used pediatric human cerebral cortical cell line HCN-2 as a neuronal model of SARS-CoV-2 infection, and, through transcriptomic analysis, our aim was to evaluate the effect of SARS-CoV-2 in this type of cells. Transcriptome analyses revealed impairment in TXN gene, resulting in deregulation of its antioxidant functions, as well as a decrease in the DNA-repairing mechanism, as indicated by the decrease in KAT5. Western blot analyses of SOD1 and iNOS confirmed the impairment of reduction mechanisms and an increase in oxidative stress. Upregulation of CDKN2A and a decrease in CDK4 and CDK6 point to the blocking of the cell cycle that, according to the deregulation of repairing mechanism, has apoptosis as the outcome. A high level of proapoptotic gene PMAIP1 is indeed coherent with neuronal death, as also supported by increased levels of caspase 3. The upregulation of cell-cycle-blocking genes and apoptosis suggests a sufferance state of neurons after SARS-CoV-2 infection, followed by their inevitable death, which can explain the neurological symptoms reported. Further analyses are required to deeply explain the mechanisms and find potential treatments to protect neurons from oxidative stress and prevent their death.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells10092189
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2661518-6
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  • 5
    Online Resource
    Online Resource
    Effects of Simvastatin on Fetal Cardiac Impairment in the Diaphragmatic Experimental Hernia Model
    S. Karger AG ; 2019
    In:  Fetal Diagnosis and Therapy Vol. 46, No. 1 ( 2019), p. 28-37
    Details
    In: Fetal Diagnosis and Therapy, S. Karger AG, Vol. 46, No. 1 ( 2019), p. 28-37
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Statins and sildenafil have been shown to exert beneficial effects in cardiac injury. We hypothesized that antenatal maternal administration of simvastatin and/or sildenafil might also promote benefits in cardiac remodeling of congenital diaphragmatic hernia (CDH). Therefore, we performed micro-CT image analysis and histology of the heart after antennal treatment in experimental nitrofen-induced CDH. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 At 9.5 days post conception (dpc), pregnant rats were exposed to nitrofen. At 16 and 20 dpc fetuses were treated with simvastatin and/or sildenafil. At 21 dpc postmortem micro-CT and autopsy were performed. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 All nitrofen-treated fetuses had a lower birth weight compared to controls; in the simvastatin-treated group, a significant improvement in CDH was noted. Impairment of the lung and liver was also noted in CDH. Compared to controls, CDH rats showed lower ventricular mass, with greater left ventricular thickness; simvastatin decreased the ventricular mass and improved wall thickness. CDH rats exhibited myocardial hypotrophy, severe vascular depression in the left ventricle, and intense interstitial edema compared to controls and nitrofen-exposed animals without CDH. In CDH, the cardiac morphology appeared deformed with left ventricular wall verticalization. Simvastatin improved cardiac myocyte appearance and heart morphology. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 The potential to treat CDH with antenatal simvastatin may improve the management of this malformation.
    Type of Medium: Online Resource
    ISSN: 1015-3837 , 1421-9964
    URL: Article
    DOI: 10.1159/000490144
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2019
    detail.hit.zdb_id: 1482292-1
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  • 6
    Online Resource
    Online Resource
    Inflammation in Obesity-Related Complications in Children: The Protective Effect of Diet and Its Potential Role as a Therapeutic Agent
    MDPI AG ; 2020
    In:  Biomolecules Vol. 10, No. 9 ( 2020-09-16), p. 1324-
    Details
    In: Biomolecules, MDPI AG, Vol. 10, No. 9 ( 2020-09-16), p. 1324-
    Abstract: Obesity is a growing health problem in both children and adults, impairing physical and mental state and impacting health care system costs in both developed and developing countries. It is well-known that individuals with excessive weight gain frequently develop obesity-related complications, which are mainly known as Non-Communicable Diseases (NCDs), including cardiovascular disease, type 2 diabetes mellitus, metabolic syndrome, non-alcoholic fatty liver disease, hypertension, hyperlipidemia and many other risk factors proven to be associated with chronic inflammation, causing disability and reduced life expectancy. This review aims to present and discuss complications related to inflammation in pediatric obesity, the critical role of nutrition and diet in obesity-comorbidity prevention and treatment, and the impact of lifestyle. Appropriate early dietary intervention for the management of pediatric overweight and obesity is recommended for overall healthy growth and prevention of comorbidities in adulthood.
    Type of Medium: Online Resource
    ISSN: 2218-273X
    URL: Article
    DOI: 10.3390/biom10091324
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2701262-1
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  • 7
    Online Resource
    Online Resource
    Liver pathological alterations in fetal rabbit model of congenital diaphragmatic hernia
    Wiley ; 2022
    In:  Congenital Anomalies Vol. 62, No. 3 ( 2022-05), p. 105-112
    Details
    In: Congenital Anomalies, Wiley, Vol. 62, No. 3 ( 2022-05), p. 105-112
    Abstract: To date, fetal liver implication is not a well‐understood phenomenon in congenital diaphragmatic hernia (CDH). We evaluated the fetal morphologic changes on liver growth after surgical procedure in CDH experimental model. A diaphragmatic defect at gestational day E25 and tracheal occlusion (TO) at E27 were surgically created in rabbit fetuses. Five experimental groups were assessed: control group, left CDH, right CDH, CDH + TO, and TO alone. Body and organ growth were measured. For histological evaluation of the CDH effect, liver sections were collected. Left‐CDH group had livers with increased leukocyte infiltration in comparison with controls ( p  = 0.02). Increased capillary sinusoid congestion and hepatocyte vacuolation were greater in left‐CDH compared with the right‐CDH group ( p  = 0.05). Capillary sinusoid congestion and interstitial edema were more evident in the left‐CDH compared with CDH + TO group ( p  = 0.05). Increases in sinusoid congestion, hepatocyte vacuolation, and interstitial edema were also greater in the CDH + TO compared with controls ( p  ≤ 0.02). Intrathoracic liver weight was higher in right‐CDH compared with left‐CDH group ( p   〈  0.001). Total lung weights (TLW) were significantly lower in both left‐CDH compared with controls ( p   〈  0.001), CDH + TO ( p  = 0.01), and TO ( p   〈  0.01) and in right‐CDH compared with CDH + TO ( p   〈  0.01) and TO ( p   〈  0.01). Decreased kidney and heart weights were also recorded. Hemodynamics and structural fetal liver changes in laterality were noted in CDH model. Regulation of intrathoracic liver weights seems to be disturbed by the absence of diaphragmic contact. Pulmonary injury is supported by the effect of a first hit, while the growth of internal organs suggests a multisystemic remodeling related to the fetal adaptation.
    Type of Medium: Online Resource
    ISSN: 0914-3505 , 1741-4520
    URL: Issue
    URL: Article
    DOI: 10.1111/cga.v62.3
    DOI: 10.1111/cga.12462
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2139944-X
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  • 8
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    Online Resource
    Does Childhood Obesity Trigger Neuroinflammation?
    MDPI AG ; 2022
    In:  Biomedicines Vol. 10, No. 8 ( 2022-08-11), p. 1953-
    Details
    In: Biomedicines, MDPI AG, Vol. 10, No. 8 ( 2022-08-11), p. 1953-
    Abstract: Childhood obesity is constantly increasing around the world, and it has become a major public health issue. Considerable evidence indicates that overweight and obesity are important risk factors for the development of comorbidities such as cognitive decline, neuroinflammation and neurodegenerative diseases. It is known that during obesity, adipose tissue undergoes immune, metabolic and functional changes which could induce a neuroinflammatory response of the central nervous system (CNS). In this context, to inspect if obesity can start to trigger the neuroinflammation from a pediatric age, we surgically collected and analyzed adipose tissue from the periumbilical area of three obese children (AT-OB) and two normal-weight children (AT-Ctrl). We considered the transcriptomic profile of our samples to detect alterations in different biological processes that might be also involved in the inflammatory and neuroinflammatory response. Our results show alterations of lipid and fatty acids metabolism in AT-OB compared to the AT-Ctrl. We also observed an onset of inflammatory response in AT-OB. Interestingly, among the genes involved in neuroinflammation, GRN and SMO were upregulated, while IFNGR1 and SNCA were downregulated. Our study highlights that obesity may trigger inflammation and neuroinflammation from a pediatric age.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines10081953
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2720867-9
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  • 9
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    Discovering Genotype Variants in an Infant with VACTERL through Clinical Exome Sequencing: A Support for Personalized Risk Assessment and Disease Prevention
    MDPI AG ; 2021
    In:  Pediatric Reports Vol. 13, No. 1 ( 2021-01-05), p. 45-56
    Details
    In: Pediatric Reports, MDPI AG, Vol. 13, No. 1 ( 2021-01-05), p. 45-56
    Abstract: Congenital anomalies may have an increased risk of noncommunicable diseases (NCDs) We performed a clinical exome analysis in an infant affected by “Vertebral, Anorectal, Cardiac, Tracheoesophageal, Genitourinary, and Limb” (VACTERL) malformation association to identify potential biomarkers that may be helpful for preventing malignancy risk or other chronic processes. Among the variants, six variants that may be linked with VACTERL were identified in the exome analysis. The variants c.501G 〉 C on OLR1 and c.-8C 〉 G on PSMA6 were previously associated with myocardial infarction. The variants c.1936A 〉 G on AKAP10 and c.575A 〉 G on PON1 are linked to defects in cardiac conduction and artery disease, respectively. Alterations in metabolism were also suggested by the variants c.860G 〉 A on EPHX2 and c.214C 〉 A on GHRL. In addition, three variants associated with colon cancer were discovered. Specifically, the reported variants were c.723G 〉 A on CCND1 and c.91T 〉 A on AURKA proto-oncogenes as well as c.827A 〉 C in the tumor suppressor PTPRJ. A further inspection identified 15 rare variants carried by cancer genes. Specifically, these mutations are located on five tumor suppressors (SDHA, RB1CC1, PTCH1, DMBT1, BCR) and eight proto-oncogenes (MERTK, CSF1R, MYB, ROS1, PCM1, FGFR2, MYH11, BRCC3) and have an allele frequency lower than 0.01 in the Genome Aggregation Database (GnomAD). We observed that the cardiac and metabolic phenotypic traits are linked with the genotype of the patient. In addition, the risk of developing neoplasia cannot be excluded a priori. Long-term surgical issues of patients with VATER syndrome could benefit from the clinical exome sequencing of a personalized risk assessment for the appearance of further disease in pubertal timing and adult age.
    Type of Medium: Online Resource
    ISSN: 2036-7503
    URL: Article
    DOI: 10.3390/pediatric13010006
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2572005-3
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  • 10
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    Mesenchymal Stromal Cells for the Treatment of Interstitial Lung Disease in Children: A Look from Pediatric and Pediatric Surgeon Viewpoints
    MDPI AG ; 2021
    In:  Cells Vol. 10, No. 12 ( 2021-11-23), p. 3270-
    Details
    In: Cells, MDPI AG, Vol. 10, No. 12 ( 2021-11-23), p. 3270-
    Abstract: Mesenchymal stromal cells (MSCs) have been proposed as a potential therapy to treat congenital and acquired lung diseases. Due to their tissue-regenerative, anti-fibrotic, and immunomodulatory properties, MSCs combined with other therapy or alone could be considered as a new approach for repair and regeneration of the lung during disease progression and/or after post- surgical injury. Children interstitial lung disease (chILD) represent highly heterogeneous rare respiratory diseases, with a wild range of age of onset and disease expression. The chILD is characterized by inflammatory and fibrotic changes of the pulmonary parenchyma, leading to gas exchange impairment and chronic respiratory failure associated with high morbidity and mortality. The therapeutic strategy is mainly based on the use of corticosteroids, hydroxychloroquine, azithromycin, and supportive care; however, the efficacy is variable, and their long-term use is associated with severe toxicity. The role of MSCs as treatment has been proposed in clinical and pre-clinical studies. In this narrative review, we report on the currently available on MSCs treatment as therapeutical strategy in chILD. The progress into the therapy of respiratory disease in children is mandatory to ameliorate the prognosis and to prevent the progression in adult age. Cell therapy may be a future therapy from both a pediatric and pediatric surgeon’s point of view.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells10123270
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2661518-6
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