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Translational Pediatrics Jun 2023Bronchopulmonary dysplasia (BPD) is the most common morbidity associated with prematurity and remains a significant clinical challenge. Bioinformatic approaches, such as... (Review)
Review
BACKGROUND AND OBJECTIVE
Bronchopulmonary dysplasia (BPD) is the most common morbidity associated with prematurity and remains a significant clinical challenge. Bioinformatic approaches, such as genomics, transcriptomics, and proteomics, have emerged as novel methods for studying the underlying mechanisms driving BPD pathogenesis. These methods can be used alongside clinical data to develop a better understanding of BPD and potentially identify the most at risk neonates within the first few weeks of neonatal life. The objective of this review is to provide an overview of the current state-of-the-art in bioinformatics for BPD research.
METHODS
We conducted a literature review of bioinformatics approaches for BPD using PubMed. The following keywords were used: "biomedical informatics", "bioinformatics", "bronchopulmonary dysplasia", and "omics".
KEY CONTENT AND FINDINGS
This review highlighted the importance of omic-approaches to better understand BPD and potential avenues for future research. We described the use of machine learning (ML) and the need for systems biology methods for integrating large-scale data from multiple tissues. We summarized a handful of studies that utilized bioinformatics for BPD in order to better provide a view of where things currently stand, identify areas of ongoing research, and concluded with challenges that remain in the field.
CONCLUSIONS
Bioinformatics has the potential to enable a more comprehensive understanding of BPD pathogenesis, facilitating a personalized and precise approach to neonatal care. As we continue to push the boundaries of biomedical research, biomedical informatics (BMI) will undoubtedly play a key role in unraveling new frontiers in disease understanding, prevention, and treatment.
PubMed: 37427053
DOI: 10.21037/tp-23-133 -
Annual Review of Genomics and Human... Aug 2023The transforming growth factor β (TGF-β) and bone morphogenetic protein (BMP) signaling pathways play a pivotal role in bone development and skeletal health. More than... (Review)
Review
The transforming growth factor β (TGF-β) and bone morphogenetic protein (BMP) signaling pathways play a pivotal role in bone development and skeletal health. More than 30 different types of skeletal dysplasia are now known to be caused by pathogenic variants in genes that belong to the TGF-β superfamily and/or regulate TGF-β/BMP bioavailability. This review describes the latest advances in skeletal dysplasia that is due to impaired TGF-β/BMP signaling and results in short stature (acromelic dysplasia and cardiospondylocarpofacial syndrome) or tall stature (Marfan syndrome). We thoroughly describe the clinical features of the patients, the underlying genetic findings, and the pathomolecular mechanisms leading to disease, which have been investigated mainly using patient-derived skin fibroblasts and mouse models. Although no pharmacological treatment is yet available for skeletal dysplasia due to impaired TGF-β/BMP signaling, in recent years advances in the use of drugs targeting TGF-β have been made, and we also discuss these advances.
Topics: Animals; Mice; Osteochondrodysplasias; Osteosclerosis; Biological Availability; Bone Development; Transforming Growth Factor beta
PubMed: 37624666
DOI: 10.1146/annurev-genom-120922-094107 -
Diagnostics (Basel, Switzerland) Sep 2023This paper presents a rare case of fetal hydrops detected at just 23 weeks of gestation in a 22-year-old woman's first pregnancy. The fetal ultrasound revealed severe...
This paper presents a rare case of fetal hydrops detected at just 23 weeks of gestation in a 22-year-old woman's first pregnancy. The fetal ultrasound revealed severe skeletal anomalies, craniofacial deformities, and thoracic abnormalities, suggesting a complex and severe skeletal dysplasia, potentially type IA Achondrogenesis-a lethal autosomal recessive condition marked by ossification delay. This case highlights the significance of advanced genetic testing, such as next-generation sequencing (NGS) and whole-genome sequencing (WGS), in diagnosing and understanding skeletal dysplasias. Skeletal dysplasias represent a group of genetic disorders that affect osteogenesis. The prevalence of this condition is 1 in 4000 births. Sadly, 25% of affected infants are stillborn, and around 30% do not survive the neonatal period. There is a wide range of rare skeletal dysplasias, each with its own specific recurrence risk, dysmorphic expression, and implications for neonatal survival and quality of life. When skeletal dysplasia is incidentally discovered during routine ultrasound screening in a pregnancy not known to be at risk of a specific syndrome, a systematic examination of the limbs, head, thorax, and spine is necessary to reach the correct diagnosis. Prenatal diagnosis of skeletal dysplasia is crucial for providing accurate counselling to future parents and facilitating the proper management of affected pregnancies. An accurate diagnosis can be a real challenge due to the wide spectrum of clinical presentations of skeletal dysplasia but advances in imaging technologies and molecular genetics have improved accuracy. Additionally, some of these skeletal dysplasias may present clinical overlap, making it especially difficult to distinguish. After the 11th revision of genetic skeletal disorder nosology, there are 771 entities associated with 552 gene mutations. The most common types of skeletal dysplasia are thanatophoric dysplasia, osteogenesis imperfect, achondroplasia, achondrogenesis, and asphyxiating thoracic dystrophy.
PubMed: 37761271
DOI: 10.3390/diagnostics13182905 -
Biomedical Reports Nov 2023Cervical myelopathy is a well-described medulla spinalis syndrome characterized by sensory disorders, such as pain, numbness, or paresthesia in the limbs, and motor... (Review)
Review
Cervical myelopathy is a well-described medulla spinalis syndrome characterized by sensory disorders, such as pain, numbness, or paresthesia in the limbs, and motor disorders, such as muscle weakness, gait difficulties, spasticity, or hyperreflexia. If left untreated, cervical myelopathy can significantly affect the quality of life of patients, while in severe cases, it can cause disability or even quadriplegia. Cervical myelopathy is the final stage of spinal cord insult and can result from transgene dysplasias of the spinal cord, and acute or chronic injuries. Spondylosis is a common, multifactor cause of cervical myelopathy and affects various elements of the spine. The development of spondylotic changes in the spine is gradual during the patient's life and the symptoms are presented at a late stage, when significant damage has already been inflicted on the spinal cord. Spondylosis is widely considered a condition affecting the middle aged and elderly. Given the fact that the population is gradually becoming older, in the near future, clinicians may have to face an increased number of patients with spondylotic myelopathy.
PubMed: 37881604
DOI: 10.3892/br.2023.1666 -
Frontiers in Pediatrics 2023
PubMed: 38027276
DOI: 10.3389/fped.2023.1303761 -
European Journal of Pediatrics Jul 2024Bronchopulmonary dysplasia (BPD) is the most common serious complication of very preterm infants (VPI) or very low birth weight (VLBW) infants. Studies implicate viral... (Meta-Analysis)
Meta-Analysis Review
Bronchopulmonary dysplasia (BPD) is the most common serious complication of very preterm infants (VPI) or very low birth weight (VLBW) infants. Studies implicate viral infections in etiopathogenesis. The aim of this study was to summarize the relationship between viral infections and BPD through a systematic review and meta-analysis. We searched PubMed, Embase, the Web of Science Core Collection, and the Cochrane Database on December 19, 2023. We included observational studies that examined the association between viral infections and BPD in preterm infants. We extracted data on study methods, participant characteristics, exposure assessment, and outcome measures. We assessed study risk of bias using the Newcastle-Ottawa Scale (NOS). We included 17 and 15 studies in the qualitative review and meta-analysis, respectively. The meta-analysis showed a significant association between viral infection and BPD diagnosed at 36 weeks postmenstrual age (odds ratio (OR): 2.42, 95% confidence interval: 1.89-3.09, 13 studies, very low certainty of evidence). In a subgroup analysis of specific viruses, cytomegalovirus (CMV) proved to be significantly associated with BPD diagnosed at 36 weeks postmenstrual age (OR: 2.34, 95% confidence interval: 1.80-3.05, 11 studies). We did not find an association between viral infection and BPD diagnosed on the 28th day of life, probably due to the small sample size of the included prospective studies. Conclusion: Viral infections, especially CMV, are associated with an increased risk of BPD in preterm infants. Methodologically reliable prospective studies with large samples are needed to validate our conclusions, and high-quality randomized controlled studies are needed to explore the effect of prevention or treatment of viral infections on the incidence of BPD. What is Known: • Studies have attempted to identify viral infections and bronchopulmonary dysplasia in preterm infants; however, results have been inconsistent. What is New: • Systematic demonstration that viral infections, particularly cytomegalovirus, are positively associated with bronchopulmonary dysplasia diagnosed in preterm infants at the 36th week of postmenstrual age. • The importance of screening for viral infections in preterm infants, especially cytomegalovirus. More high-quality studies should be produced in the future to investigate the causal relationship between viral infections and bronchopulmonary dysplasia.
Topics: Humans; Bronchopulmonary Dysplasia; Infant, Newborn; Infant, Premature; Virus Diseases; Infant, Very Low Birth Weight
PubMed: 38634889
DOI: 10.1007/s00431-024-05565-9 -
American Journal of Respiratory Cell... Oct 2023Worldwide, the incidence of both preterm births and chronic lung disease of infancy, or bronchopulmonary dysplasia, remains high. Infants with bronchopulmonary dysplasia...
Worldwide, the incidence of both preterm births and chronic lung disease of infancy, or bronchopulmonary dysplasia, remains high. Infants with bronchopulmonary dysplasia have larger and fewer alveoli, a lung pathology that can persist into adulthood. Although recent data point to a role for hypoxia-inducible factor-1α (HIF-1α) in mediating pulmonary angiogenesis and alveolarization, the cell-specific role of HIF-1α remains incompletely understood. Thus, we hypothesized that HIF-1α, in a distinct subset of mesenchymal cells, mediates postnatal alveolarization. To test the hypothesis, we generated mice with a cell-specific deletion of HIF-1α by crossing SM22α promoter-driven Cre mice with HIF-1α mice (SM22α-HIF-1α), determined SM-22α-expressing cell identity using single-cell RNA sequencing, and interrogated samples from preterm infants. Deletion of HIF-1α in SM22α-expressing cells had no effect on lung structure at day 3 of life. However, at 8 days, there were fewer and larger alveoli, a difference that persisted into adulthood. Microvascular density, elastin organization, and peripheral branching of the lung vasculature were decreased in SM22α-HIF-1α mice, compared with control mice. Single-cell RNA sequencing demonstrated that three mesenchymal cell subtypes express SM22α: myofibroblasts, airway smooth muscle cells, and vascular smooth muscle cells. Pulmonary vascular smooth muscle cells from SM22α-HIF-1α mice had decreased angiopoietin-2 expression and, in coculture experiments, a diminished capacity to promote angiogenesis that was rescued by angiopoietin-2. Angiopoietin-2 expression in tracheal aspirates of preterm infants was inversely correlated with overall mechanical ventilation time, a marker of disease severity. We conclude that SM22α-specific HIF-1α expression drives peripheral angiogenesis and alveolarization in the lung, perhaps by promoting angiopoietin-2 expression.
Topics: Animals; Humans; Infant, Newborn; Mice; Angiopoietin-2; Bronchopulmonary Dysplasia; Hypoxia-Inducible Factor 1, alpha Subunit; Infant, Premature; Lung
PubMed: 37290124
DOI: 10.1165/rcmb.2023-0045OC -
BMC Veterinary Research Oct 2023Human and veterinary medicine have historically presented many medical areas of potential synergy and convergence. Mechanical osteoarthritis (MOA) is characterized by a... (Review)
Review
Human and veterinary medicine have historically presented many medical areas of potential synergy and convergence. Mechanical osteoarthritis (MOA) is characterized by a gradual complex imbalance between cartilage production, loss, and derangement. Any joint instability that results in an abnormal overload of the joint surface can trigger MOA. As MOA has a prevailing mechanical aetiology, treatment effectiveness can only be accomplished if altered joint mechanics and mechanosensitive pathways are normalized and restored. Otherwise, the inflammatory cascade of osteoarthritis will be initiated, and the changes may become irreversible. The management of the disease using non-steroidal anti-inflammatory drugs, analgesics, physical therapy, diet changes, or nutraceuticals is conservative and less effective. MOA is a determinant factor for the development of hip dysplasia in both humans and dogs. Hip dysplasia is a hereditary disease with a high incidence and, therefore, of great clinical importance due to the associated discomfort and significant functional limitations. Furthermore, on account of analogous human and canine hip dysplasia disease and under the One Medicine concept, unifying veterinary and human research could improve the well-being and health of both species, increasing the acknowledgement of shared diseases. Great success has been accomplished in humans regarding preventive conservative management of hip dysplasia and following One Medicine concept, similar measures would benefit dogs. Moreover, animal models have long been used to better understand the different diseases' mechanisms. Current research in animal models was addressed and the role of rabbit models in pathophysiologic studies and of the dog as a spontaneous animal model were highlighted, denoting the inexistence of rabbit functional models to investigate therapeutic approaches in hip MOA.
Topics: Animals; Humans; Dogs; Rabbits; Osteoarthritis, Hip; Hip Dislocation; Hip Dysplasia, Canine; Joint Instability; Dietary Supplements; Dog Diseases
PubMed: 37875898
DOI: 10.1186/s12917-023-03777-z