Molecular and cellular pediatrics最新文献

{"title":"Novel WAC gene variant identified in the first documented case of DeSanto-Shinawi Syndrome in India.","authors":"Aradhana Dwivedi, Lakshita Chauhan, Pramod Kumar, Aashna Nanda, V Y Jayakrishnan","doi":"10.1186/s40348-025-00193-1","DOIUrl":"https://doi.org/10.1186/s40348-025-00193-1","url":null,"abstract":"<p><strong>Background: </strong>DeSanto-Shinawi Syndrome (DESSH) is a rare neurodevelopmental disorder characterized by intellectual disability, behavioral abnormalities, and distinctive dysmorphic features, linked to likely pathogenic/pathogenic variants in the WAC gene. We report the first documented case of DESSH in India, identified in a 3-year-old male presenting with global developmental delay and coarse facies.</p><p><strong>Results: </strong>Exome sequencing revealed a novel heterozygous nonsense likely pathogenic variant (c.1661 C>A(p.Ser554*)) in the WAC gene, expanding the genotypic spectrum associated with this condition. We employed computational methodologies to understand the effects of this novel variant on protein structure and function. In-silico prediction score suggested protein truncation due to the c.1661 C>A (p.Ser554*) variation in the WAC gene, expected to result in a loss of normal protein function.</p><p><strong>Conclusion: </strong>The findings advocate for increased awareness and genetic testing in atypical cases to facilitate accurate diagnosis and management. This case underscores the importance of considering DESSH in the differential diagnosis of similar neurodevelopmental disorders and enhances our understanding of the genetic diversity within the WAC gene.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"12 1","pages":"7"},"PeriodicalIF":2.4,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progress of personalized medicine of cystic fibrosis in the times of efficient CFTR modulators.","authors":"Burkhard Tümmler, Sophia Theres Pallenberg, Anna-Maria Dittrich, Simon Y Graeber, Lutz Naehrlich, Olaf Sommerburg, Marcus A Mall","doi":"10.1186/s40348-025-00194-0","DOIUrl":"https://doi.org/10.1186/s40348-025-00194-0","url":null,"abstract":"<p><strong>Background: </strong>Cystic fibrosis (CF) is a systemic disorder of exocrine glands that is caused by mutations in the CFTR gene.</p><p><strong>Main body: </strong>The basic defect in people with CF (pwCF) leads to impaired epithelial transport of chloride and bicarbonate that can be assessed by CFTR biomarkers, i.e. the β-adrenergic sweat rate and sweat chloride concentration (SCC), chloride conductance of the nasal respiratory epithelium (NPD), urine secretion of bicarbonate, intestinal current measurements (ICM) of chloride secretory responses in rectal biopsies and in bioassays of chloride transport in organoids or cell cultures. CFTR modulators are a novel class of drugs that improve defective posttranslational processing, trafficking and function of mutant CFTR. By April 2025, triple combination therapy with the CFTR potentiator ivacaftor (IVA) and the CFTR correctors elexacaftor (ELX) and tezacaftor (TEZ) has been approved in Europe for the treatment of all pwCF who do not carry two minimal function CFTR mutations. Previous phase 3 and post-approval phase 4 studies in pwCF who harbour one or two alleles of the major mutation F508del consistently reported significant improvements of lung function and anthropometry upon initiation of ELX/TEZ/IVA compared to baseline. Normalization of SCC, NPD and ICM correlated with clinical outcomes on the population level, but the restoration of CFTR function was diverse and not predictive for clinical outcome in the individual patient. Theratyping of non-F508del CF genotypes in patient-derived organoids and cell cultures revealed for most cases clinically meaningful increases of CFTR activity upon exposure to ELX/TEZ/IVA. Likewise, every second CF patient with non-F508del genotypes improved in SCC and clinical outcome upon exposure to ELX/TEZ/IVA indicating that triple CFTR modulator therapy is potentially beneficial for all pwCF who do not carry two minimal function CFTR mutations. This group who is not eligible for CFTR modulators may opt for gene addition therapy in the future, as the first-in-human trial with a recombinant lentiviral vector is underway.</p><p><strong>Future directions: </strong>The upcoming generation of pwCF will probably experience a rather normal life in childhood and adolescence. To classify the upcoming personal signatures of CF disease in the times of efficient modulators, we need more sensitive CFTR biomarkers that address the long-term course of airway and gut microbiome, host defense, epithelial homeostasis and multiorgan metabolism.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"12 1","pages":"6"},"PeriodicalIF":2.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12050259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding the role of extracellular vesicles in pathogenesis of cystic fibrosis.","authors":"Priya Kalsi, Nikhil Gupta, Gitanjali Goyal, Himanshu Sharma","doi":"10.1186/s40348-025-00190-4","DOIUrl":"https://doi.org/10.1186/s40348-025-00190-4","url":null,"abstract":"<p><strong>Background: </strong>Intercellular communication is a critical process that ensures cooperation between distinct cell types and maintains homeostasis. In the past decades, extracellular vesicles (EVs) have been recognized as key components in cell-to-cell communication. These EVs carry multiple factors such as active enzymes, metabolites, nucleic acids and surface molecules that can alter the behavior of recipient cells. Thus, the role of EVs in exacerbating disease pathology by transporting inflammatory mediators, and other molecular signals that contribute to chronic inflammation and immune dysregulation in various diseases including cystic fibrosis (CF) is well documented.</p><p><strong>Main body: </strong>CF is a genetic disorder characterized by chronic inflammation and persistent infections, primarily affecting the respiratory system. This review explores the multifaceted roles of EVs in CF lung disease, focusing on their biogenesis, cargo, and contributions to disease progression. It is well known that CF results from mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene, leading to defective ion transport, thick mucus secretion, and a propensity for bacterial infections. However, it has been observed that EVs derived from CF patients carry altered molecular cargo, including proteins, lipids, RNA, and DNA, which can exacerbate these conditions by promoting inflammation, and modulating immune responses. Beyond their pathogenic roles, EVs also hold significant therapeutic potential. Their natural ability to transfer bioactive molecules positions them as promising vectors for delivering therapeutic agents, such as gene therapy constructs and anti-inflammatory compounds. Accordingly, a study has shown that these EVs can act as a carrier molecule for transport of functional CFTR mRNA, helping to restore proper chloride ion channel function by correcting defective CFTR proteins in affected cells.</p><p><strong>Conclusion: </strong>This review aims to summarize the role of EVs and their molecular cargo in pathogenesis of CF lung disease via modulation of intracellular signaling leading to persistent inflammation and increased disease severity. We also explored the mechanisms of EV biogenesis, cargo selection, and their effects on recipient cells which may provide novel insights into CF pathogenesis and open new avenues for EV-based therapies aimed at improving disease management.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"12 1","pages":"5"},"PeriodicalIF":2.4,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hand hygiene versus additional non-sterile gloves and gowns use to prevent sepsis in preterm infants colonized with multi-resistant drug bacteria: the study protocol of the cluster-randomized, cross-over, non-inferiority BALTIC trial.","authors":"Kirstin Faust, Clara Haug, Julia Pagel, Reinhard Jensen, Anja Stein, Ursula Felderhoff-Müser, David Frommhold, Kirsten Brebach, Christian Wieg, Georg Hillebrand, Barbara Naust, Esther Schmidt, Lutz Koch, Susanne Schmidtke, Arne Simon, Michael Zemlin, Sascha Meyer, Christopher Scholzen, Natascha Köstlin-Gille, Christian Gille, Ann-Carolin Longardt, Manuela Kärlin, Mirjam Lusga, Wolfgang Göpel, Manuel Krone, Stefanie Kampmeier, Franziska Strecker, Dennis Nurjadi, Inke R König, Egbert Herting, Jan Rupp, Christoph Härtel","doi":"10.1186/s40348-025-00192-2","DOIUrl":"10.1186/s40348-025-00192-2","url":null,"abstract":"<p><strong>Background: </strong>Infections are highly relevant for neonatal mortality and long-term morbidities in survivors. Therefore, it is an urgent need to optimize and evaluate infection prevention and control (IPC) strategies. Several infection outbreaks in German neonatal intensive care units (NICUs) required rapid responses by hospitals and improved future preparedness. As a consequence, German authorities recommended weekly colonization screening on NICUs. This screening aims to detect multidrug-resistant organisms (MDRO) and bacteria with high transmissibility. According to these guidelines, infants colonized with multiresistant gram-negative (MRGN) bacteria with in-vitro resistance to piperacillin and cephalosporins (2MRGN) should be cared wearing non-sterile gloves and gowns in addition to standard hygiene precautions. Whether these extended IPC measures have an individual benefit for infants or contribute to the prevention of infection outbreaks has not yet been scientifically proven. This study aims to evaluate the effect of hand desinfection as compared to hand desinfection + gloves and gowns (barrier care) for the care of 2MRGN colonized infants in NICUs on infection and transmission rates through a multicenter, cluster randomized controlled trial (BALTIC study, Barrier protection to lower transmission and infection rates with Gram-negative 2-MRGN in preterm children).</p><p><strong>Methods: </strong>12 participating NICUs were randomly allocated to two trial arms: receiving the intervention \"standard precautions with a special focus on hand desinfection\" or control (standard precautions \"plus\" barrier care) for the care of 2MRGN positive infants. Cross over was performed after 12 months for another 12 months per site. Primary outcome was the rate of healthcare-associated (HA) Gram-negative bloodstream infections. Secondary outcomes included transmission rate with screening relevant bacteria, overall rate of clinical and culture-proven infections, number of antibiotic cycles and desinfectant use. Regular trainings and hygiene audits are standardized co-interventions.</p><p><strong>Benchmarking results: </strong>According to our single center data, 9.3% of NICU-treated infants are colonized with 2MRGN during their hospital stay. BALTIC randomized the first center in October 2020 and finished data collection including close-out monitoring in January 2024. Data analysis will be completed in May 2025.</p><p><strong>Conclusions: </strong>BALTIC should contribute to better evidence on the effectiveness of hand desinfection and extended barrier precautions in critically ill newborns. Further benefits include comprehensive multi-center data collection on MDRO colonization dynamics, an improved awareness on IPC strategies and establishment of network platforms including antimicrobial stewardship programs.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"12 1","pages":"4"},"PeriodicalIF":2.4,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PPP5C pathogenic variant identified: a potential key to gaining insight into developmental and epileptic encephalopathy?","authors":"Raffaele Falsaperla, Annamaria Sapuppo, Xena Giada Pappalardo, Roberta Rizzo, Roberta Rocca, Gaia Fusto, Silvia Marino, Vincenzo Sortino, Lucia Saccuzzo, Martino Ruggieri, Marco Fichera","doi":"10.1186/s40348-025-00191-3","DOIUrl":"10.1186/s40348-025-00191-3","url":null,"abstract":"<p><strong>Background: </strong>Emerging evidence suggesting a possible link between the PPP5C gene (protein phosphatase 5 catalytic subunit; OMIM#600658) and developmental and epileptic encephalopathy (DEE, OMIM#308350), although the clinical significance of pathogenic variants in this gene remains unclear. PPP5C is a member of the protein phosphatase catalytic subunit family, which is involved in various signaling pathways governing cell growth, differentiation, and responses to hormonal signals or cellular stress. To date, only one case with a PPP5C variant has been reported, associated with a severe neurological phenotype, including microcephaly, failure to thrive, and early-onset seizures.</p><p><strong>Results: </strong>We report a 12-year-old girl affected by epilepsy and learning disorders. At the age of five, she presented convulsive status epilepticus with respiratory failure at onset and she started anticonvulsant therapy with Levetiracetam with a significant improvement. Genetic analysis revealed a de novo heterozygous missense variant of PPP5C gene (c.202 C > T: p.Arg68Cys), which had not been previously described in the literature.</p><p><strong>Conclusion: </strong>This case expands the phenotypic spectrum associated with PPP5C variants, highlighting the potential role of this gene inneurological disorders. Our findings may provide some valuable insights into the spectrum of phenotypic manifestations linked to this gene less investigated in neuropediatrics.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"12 1","pages":"3"},"PeriodicalIF":2.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of the Effectiveness of Paracetamol and Ibuprofen in the Management of Patent Ductus Arteriosus in Preterm Neonates: A Randomized Controlled Trial.","authors":"S Mohsin Ali Shah, Shaista Azeem Khan, Faran Sadiq, Ruba Gul, Faizan Sadiq, Misbah Ullah Khan, Muhammad Khalid Khan, Faryal Uzma, Arooj Khan, Sabir Khan","doi":"10.1186/s40348-025-00189-x","DOIUrl":"10.1186/s40348-025-00189-x","url":null,"abstract":"<p><strong>Background: </strong>Patent ductus arteriosus is one of the most common cardiac conditions affecting the neonates. Considering the lack of studies done on this topic in healthcare settings in Khyber Pakhtunkhwa province, this study aims to find out the comparative effectiveness of paracetamol and ibuprofen in management of PDA in our healthcare setting to conclude a better management option for the condition.</p><p><strong>Objective: </strong>To find and compare the effectiveness of paracetamol and ibuprofen in the closure of patent ductus arteriosus in preterm neonates.</p><p><strong>Methodology: </strong>This randomized controlled trial was conducted in the Department of Nursery and Neonatal Intensive Care Unit, Khyber Teaching Hospital, Peshawar, Pakistan, from 10th April 2024 to 10th October 2024. A total of 256 neonates of both genders with patent ductus arteriosus were included. Group A received oral paracetamol, and Group B received oral ibuprofen. The effectiveness of the treatments was evaluated at the end of the treatment period.</p><p><strong>Results: </strong>The age range in this study was from 48 to 96 h, with a mean age of 71.79 ± 13.10 h in Group A and 73.40 ± 11.81 h in Group B. Efficacy was observed in 107 (83.6%) patients in Group A compared to 90 (70.3%) patients in Group B, showing a statistically significant difference (P = 0.011).</p><p><strong>Conclusion: </strong>Our study has concluded that paracetamol is more effective than ibuprofen in closing patent ductus arteriosus. The trials were retrospectively registered at NIH Trial Registry (NCT06601114) https://clinicaltrials.gov/study/NCT06601114 dated 15/09/2024.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"12 1","pages":"2"},"PeriodicalIF":2.4,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic delay in cerebral creatine deficiency disorders: lessons learned from a cross-sectional single center study, and guanidinoacetate and creatine measurements in Switzerland between 2015 and 2023.","authors":"Christina Kaufman, Anaïs D'Andrea, Annette Hackenberg, Martin Poms, Olivier Braissant, Johannes Häberle","doi":"10.1186/s40348-024-00188-4","DOIUrl":"10.1186/s40348-024-00188-4","url":null,"abstract":"<p><strong>Background: </strong>Cerebral creatine deficiency disorders (CCDD) are rare diseases caused by defects in the enzymes L-arginine: glycine amidinotransferase (AGAT) or guanidinoacetate-N-methyltransferase (GAMT), which are involved in synthesis of creatine; or by a defect in the creatine transporter (CRTR), which is essential for uptake of creatine as important energy source into the target cells. Patients with CCDD can present with a variety of unspecific symptoms: global developmental delay, speech-language disorder, behavioral abnormalities and seizures. Early treatment initiation is essential in AGAT and GAMT deficiencies to achieve a favorable outcome. This study describes the CCDD patient cohort in a single center, and an analysis of the referrals to two Swiss laboratories in Lausanne and Zurich between 2015 and 2023 for the two marker metabolites guanidinoacetate and creatine.</p><p><strong>Results: </strong>The patient cohort comprised 6 patients (defects: 2 GAMT, 4 CRTR), who were initially seen by different subspecialties depending on first symptoms. There was a diagnostic and therapeutic delay between 3 and 32 months (mean 13.8). Numbers of biomarker requests showed a constant increase during the study period, with a majority of tests performed in urine, the preferred sample for CCDD detection. Almost all samples (93.3%) were sent in by large hospitals (mainly from neurology, developmental pediatrics and metabolism) and only few (5.2%) by pediatricians in private practice, although those usually see the patients first.</p><p><strong>Conclusions: </strong>The data from this study demonstrate a relevant delay in identifying patients with these rare conditions, and a predominance of biomarker analysis requested from pediatric subspecialties that are involved in patient management often long after occurrence of symptoms. To reduce the diagnostic delay and the outcome of patients, the current practice of sample referral should be reflected and first-contact healthcare providers should be encouraged to initiate selective screening.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"12 1","pages":"1"},"PeriodicalIF":2.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myocardial mRNA expression of interleukin-6 and hypoxia inducible factor-1α in neonates with congenital cardiac defects.","authors":"Nesrine Farhat, Jaime Vazquez-Jimenez, Ruth Heying, Marie-Christine Seghaye","doi":"10.1186/s40348-024-00187-5","DOIUrl":"10.1186/s40348-024-00187-5","url":null,"abstract":"<p><strong>Background: </strong>In neonates with congenital heart disease (CHD), myocardial remodelling involves activation of inflammatory pathways. The role of hypoxemia related pathways is however unknown. This study was therefore designed to investigate myocardial mRNA expression of interleukin (IL)-6 and hypoxia-inducible factor (HIF)-1α in neonates with CHD and analyse its influence on post-operative outcome.</p><p><strong>Results: </strong>14 neonates with CHD scheduled for open cardiac surgery were studied. In group 1 (n = 5), pre-operative transcutaneous arterial oxygen saturation (SaO₂) was ≤ 85% and in group 2 (n = 9) > 85%. Expression of IL-6- and HIF-1α-mRNA was studied on right atrial biopsy by RT-PCR and corelated to post-operative (po) outcome. Group 1 patients showed higher mean arterial blood pressure (MAP) and lower glycaemia 4 h po (p = 0.047 and p = 0.021, respectively). In the whole cohort, SaO₂ correlated negatively with MAP (Pearson R: -0.662, p = 0.010). mRNA coding for IL-6 and HIF-1α was detected in the myocardium of all neonates independently of age, gender, or type of CHD. IL6-mRNA expression was not influenced by pre-operative hypoxemia but was associated with higher lactate levels in early po period (Pearson R: 0,611, p = 0,020). HIF-1α-mRNA expression correlated negatively with pre-operative SaO₂ (Pearson R: -0.551, p = 0.04) and with aspartate aminotransferase levels 4 h po (Pearson R: 0.625, p = 0.017).</p><p><strong>Conclusion: </strong>Our study shows that besides inflammatory pathways, hypoxemia related pathways are activated in the myocardium of neonates with CHD. Myocardial expression of both IL-6-mRNA and HIF-1α-mRNA relates to biological markers of a worse po outcome.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"11 1","pages":"14"},"PeriodicalIF":2.4,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of steroid therapy on pediatric acute liver failure: prognostic implication and interplay between TNF-α and miR-122.","authors":"Rania M El-Shanawany, Eman A El-Maadawy, Hanaa A El-Araby, Roba M Talaat","doi":"10.1186/s40348-024-00185-7","DOIUrl":"10.1186/s40348-024-00185-7","url":null,"abstract":"<p><strong>Background: </strong>Acute liver failure (ALF) is a rare illness marked by rapid deterioration of liver function, leading to high morbidity and mortality rates, particularly in children. While steroids have been observed to correlate with improved survival, evidence supporting their efficacy in ALF children remains limited. miR-122, a liver-specific microRNA, plays a pivotal role in liver pathology, with its expression significantly altered in various liver diseases. Thus, it is considered a potential biomarker for disease progression, aids in prognosis, and identifies therapeutic targets. Our study aims to assess the expression of miR-122 in 24 children with ALF, both before and after steroid therapy, alongside its relationship with tumor necrosis factor-α (TNF-α), to better understand its potential role in treatment response and disease outcomes. miR-122 levels were determined using quantitative real-time RT-PCR (qRT-PCR), while TNF-α levels were assessed using enzyme-linked immunosorbent assay (ELISA) in patient sera.</p><p><strong>Results: </strong>In ALF children who survived after steroid treatment, miR-122 was markedly decreased compared to both pre-treatment levels (p = 0.003) and levels in deceased patients (p = 0.01). In addition, TNF-α levels significantly increased in surviving patients compared to pre-treatment levels (p = 0.008) and levels in deceased children (p = 0.028). A negative correlation was observed between TNF-α and miR-122 following steroids (r=-0.46, p = 0.04). miR-122 demonstrated 72% sensitivity and 67% specificity in distinguishing survivors and non-survivors, as indicated by its receiver-operated characteristic curve. A positive correlation was found between miR-122 before steroid therapy and both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) before (r = 0.641, p = 0.002 and r = 0.512, p = 0.02, respectively) and after (r = 0.492, p = 0.03 and r = 0.652, p = 0.003, respectively) steroids treatment.</p><p><strong>Conclusion: </strong>Our data implies that lower miR-122 levels in steroids-treated ALF children are associated with a better outcome. Although miR-122 is not a strong standalone marker, it could be valuable in a biomarker panel. The increased TNF-α levels and decreased miR-122 expression indicate their involvement in the disease's pathophysiology. More studies are needed to validate our results.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"11 1","pages":"13"},"PeriodicalIF":2.4,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-stratification reveals age-specific intestinal microbiota signatures in juvenile idiopathic arthritis.","authors":"Lisa Budzinski, Toni Sempert, Leonie Lietz, René Maier, Gi-Ung Kang, Anne Sae Lim von Stuckrad, Carl Christoph Goetzke, Maria Roth, Aayushi Shah, Amro Abbas, Katrin Lehman, Kathleen Necke, Stefanie Bartsch, Ute Hoffmann, Mir-Farzin Mashreghi, Robert Biesen, Tilmann Kallinich, Hyun-Dong Chang","doi":"10.1186/s40348-024-00186-6","DOIUrl":"10.1186/s40348-024-00186-6","url":null,"abstract":"<p><strong>Objective: </strong>Juvenile Idiopathic Arthritis (JIA) comprises diverse chronic inflammatory conditions driven by malfunction of the immune system. The intestinal microbiota is considered a crucial environmental factor correlating with chronic inflammatory diseases, and for JIA certain alterations in the microbiota have already been described.</p><p><strong>Methods: </strong>Here, we have characterized intestinal microbiota samples from 54 JIA patients and 38 pediatric healthy controls by conventional 16S rRNA sequencing and by single-cell analysis for phenotypic features by multi-parameter microbiota flow cytometry (mMFC), which complements the population-based taxonomic profiling with the characterization of individual bacterial cells.</p><p><strong>Results: </strong>We found age to be a crucial confounder in microbiota analyses of JIA patients. Age stratification revealed specific microbiota alterations neglected by the general comparison of JIA patients and pediatric controls.</p><p><strong>Conclusion: </strong>Age groups presented distinct taxonomic profiles and microbiota phenotypic signatures which transitioned with age, highlighting changes in the microbiota-immune system interaction with age.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"11 1","pages":"12"},"PeriodicalIF":2.4,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142803936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}