Pediatric Research最新文献

{"title":"Anlotinib mediates intrinsic drug resistance in hepatoblastoma through the GAD1/GABA pathway.","authors":"Haijin Huang, Yanping Feng, Yuhui Xu, Jianping Liu, Wei Peng, Linshan Zeng, Yong Zeng, Jinping Liu, Xiao He, Haijin Liu","doi":"10.1038/s41390-025-04074-1","DOIUrl":"https://doi.org/10.1038/s41390-025-04074-1","url":null,"abstract":"<p><strong>Background: </strong>Intrinsic resistance reduces the effectiveness of many anticancer therapies. Anlotinib, a small-molecule multi-targeted tyrosine kinase inhibitor, has shown potential in treating hepatoblastoma. This study investigates the role of γ-aminobutyric acid (GABA) in anlotinib resistance using in vivo and in vitro models.</p><p><strong>Methods: </strong>HuH-6 hepatoblastoma cells were implanted into nude mice to assess the effects of anlotinib on tumor growth. Neurotransmitter-targeted metabolomics was performed to analyze neurotransmitter metabolism in xenograft tumor tissues. In vitro, HuH-6 and HepG2 cells were treated with anlotinib to evaluate changes in GABA synthesis, degradation, and associated protein expression.</p><p><strong>Results: </strong>Anlotinib significantly inhibited HuH-6 tumor growth but was less effective than cisplatin. Neurotransmitter-targeted metabolomics showed tumors treated with anlotinib exhibited increased GABA levels. Anlotinib treatment also upregulated the protein expression of GAD1, a key enzyme in GABA synthesis. In vitro, anlotinib treatment enhanced GABA release and GAD1 expression in hepatoblastoma cells. Exogenous GABA stimulation promoted cell proliferation in vitro and tumor growth in vivo. Notably, GAD1 knockdown enhanced anlotinib's inhibitory effects on hepatoblastoma in vitro and in vivo.</p><p><strong>Conclusion: </strong>Anlotinib induces intrinsic resistance in hepatoblastoma by upregulating GAD1 and increasing GABA accumulation. Targeting GAD1 may enhance anlotinib's therapeutic efficacy and help overcome resistance.</p><p><strong>Impact: </strong>Anlotinib upregulates GAD1 to enhance GABA synthesis, driving intrinsic resistance in hepatoblastoma by activating tumor-promoting GABA signaling in the tumor microenvironment. First identification of the GAD1/GABA axis as a critical mediator of anlotinib resistance, expanding understanding of neurotransmitter-driven drug tolerance in pediatric cancers. GAD1 knockdown synergizes with anlotinib to overcome resistance, establishing a combinatorial strategy to enhance antitumor efficacy in preclinical models. Proposes targeting GABA metabolism to optimize anlotinib-based therapies, addressing unmet needs in refractory hepatoblastoma treatment.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduction of neonatal intensive care unit (NICU) parental perceptions of child vulnerability and risk of vulnerable child syndrome utilizing cognitive behavioral therapy: randomized controlled trial.","authors":"Margaret K Hoge, Elizabeth Heyne, Steven Brown, Roy Heyne, Richard J Shaw, Lina Chalak","doi":"10.1038/s41390-025-04094-x","DOIUrl":"https://doi.org/10.1038/s41390-025-04094-x","url":null,"abstract":"<p><strong>Background: </strong>Neonatal intensive care unit (NICU) parental emotional trauma can distort parental perceptions of child vulnerability (PPCV), resulting in adverse child developmental outcomes, known as Vulnerable Child Syndrome (VCS). We hypothesize utilizing a novel trauma-informed cognitive behavioral therapy (CBT) intervention will reduce PPCV in premature NICU infants' parents.</p><p><strong>Methods: </strong>English and Spanish speaking parents of preterm infants (<31 weeks gestational age) were randomized from April 2019 to March 2020 to receive either a 5-session trauma-informed CBT intervention created for this study educating parents on PPCV concepts, or to a control group receiving standard of care. Principal outcome measure was PPCV change measured by the Vulnerable Baby Scale (VBS) scores from enrollment (33 weeks post menstrual age) to study end (6 months chronological age).</p><p><strong>Results: </strong>8 control and 12 intervention families completed the study (n = 42 randomized) due to COVID-19 mandatory research pause. CBT intervention group had a median VBS decrease of 6 points vs. 0 point in controls (P = 0.07). Post-hoc Bayesian analysis of VBS PPCV reduction (utilized due to limited n) favored CBT to control by 95%.</p><p><strong>Conclusion: </strong>This is the first parental trauma-informed CBT intervention to demonstrate a PPCV decrease and lower risk of development of VCS in a high-risk NICU population.</p><p><strong>Impact: </strong>A brief intervention shows promise in fostering improved parenting perceptions, behaviors, and outcomes. NICU parental trauma negatively impacts parental perceptions of child vulnerability and their parenting styles resulting in poor child developmental outcomes, summarized as Vulnerable Child Syndrome (VCS). Currently, there is no effective treatment standard of care to address this important clinical issue. This manuscript contributes to our understanding of the following: Trauma-informed cognitive behavioral therapy lowers parents' perceptions of vulnerability in an at-risk NICU population. This is the first published intervention to demonstrate efficacy in reducing NICU parental perceptions of child vulnerability, a key contributor to VCS. Implementation of this intervention with NICU families has the potential to reduce the risk of VCS and improve parent-child outcomes and child developmental outcomes.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov identifier: NCT03906435.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk factors for severe pertussis in children and the application of exchange transfusion.","authors":"Qihong Chen, Lihua Lin, Shuping Xiong, Dandan Ge, Yungang Yang","doi":"10.1038/s41390-025-04118-6","DOIUrl":"https://doi.org/10.1038/s41390-025-04118-6","url":null,"abstract":"<p><strong>Objective: </strong>To identify risk factors for severe pertussis and assess the efficacy of exchange transfusion in children.</p><p><strong>Methods: </strong>We analyzed pediatric pertussis cases, comparing mild and severe presentations using hospital data on demographics, symptoms, lab findings, echocardiography, and complications, and employed ROC analysis to determine severe pertussis risk factors.</p><p><strong>Results: </strong>Our study analyzed 119 mild and 64 severe pertussis cases, with severe cases characterized by earlier onset, spasmodic cough, shortness of breath, and rales. Risk factors for severity included lack of DTaP vaccination and pulmonary hypertension. Severe cases also showed higher WBC and lymphocyte counts and more mixed infections. Logistic regression identified shortness of breath, no DTaP, younger age, and high WBC as severity predictors (P < 0.05). ROC analysis predicted severity with age < 3.68 months and WBC > 27.93 × 10⁹/L (AUC = 0.606, 0.725; P < 0.05). Exchange transfusion in patients with rising WBC and shortness of breath normalized pulmonary hypertension and led to recovery.</p><p><strong>Conclusion: </strong>Clinicians should closely monitor unvaccinated children with shortness of breath, onset before 3.68 months, and WBC > 27.93 × 10⁹/L for severe pertussis risk. Exchange transfusion is advised for those with WBC > 40 × 10⁹/L and pulmonary hypertension, showing significant therapeutic benefit.</p><p><strong>Impact: </strong>This study delineates four key predictors of severe pertussis in children: younger age, lack of DTaP vaccination, shortness of breath, and elevated white blood cell (WBC) counts. We establish WBC > 27.93 × 10⁹/L as a robust quantitative biomarker for severity prediction (AUC = 0.725), providing clinicians with an objective threshold to prioritize intensive monitoring and intervention. Exchange transfusion demonstrates efficacy in reducing WBC levels and resolving pulmonary hypertension in critical cases. These findings reinforce the imperative of DTaP vaccination to prevent severe disease and inform evidence-based management protocols.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breastfeeding beyond infancy supports adequate growth, development, and nutritional intake.","authors":"Meghan R Crimmins, Clark R Sims, David K Williams, Aline Andres, Sarah Sobik","doi":"10.1038/s41390-025-04111-z","DOIUrl":"https://doi.org/10.1038/s41390-025-04111-z","url":null,"abstract":"<p><strong>Background and objective: </strong>The objective of this study was to examine the associations of breastfeeding beyond infancy (BBI, >1 year) on toddler growth, development, and diet.</p><p><strong>Methods: </strong>Participants (n = 185) of a prospective longitudinal study were categorized into 3 groups: formula fed (FF, N = 22), breastfed up to 12 months (BF, N = 108), and breastfed up to 24 months (PBF, N = 55). Data collected included demographics, anthropometrics, toddler Healthy Eating Index (HEI), Child Feeding Questionnaire (CFQ), and Bayley scales of infant and toddler development (BSID).</p><p><strong>Results: </strong>At age 24 months, linear modeling showed PBF children had lower weight-for-length z-scores in comparison to both FF and BF children. FF infants had lower HEI scores for total fruit compared to BF and PBF infants, whereas PBF infants had higher seafood HEI scores. Feeding responsibility was lower in BF parents than FF parents. Restriction was lower in BF and FF groups compared to PBF, and pressure feeding was less common in PBF. Developmental testing revealed no significant differences between the three groups.</p><p><strong>Conclusion: </strong>These results strengthen evidence that BBI supports adequate childhood growth, nutritional status, and development. Further studies are needed to evaluate the effect of BBI on health status in childhood.</p><p><strong>Clinical trial id: </strong>#NCT01131117 IMPACT: This research supports the current recommendations to continue breastfeeding up to 24 months. This research indicates that breastfeeding beyond infancy supports adequate growth, nutritional status, and overall development. This article adds to the growing body of literature that breastfeeding beyond 12 months should be supported. This article is one of the first prospective longitudinal studies to investigate breastfeeding beyond infancy.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Burdens of interpersonal violence in adolescents and young adults.","authors":"Leiwen Fu, Ke Liu, Bingyi Wang, Tian Tian, Zhen Lu, Weijie Zhang, Junye Bian, Huachun Zou","doi":"10.1038/s41390-025-04114-w","DOIUrl":"https://doi.org/10.1038/s41390-025-04114-w","url":null,"abstract":"<p><strong>Background: </strong>Interpersonal violence (IV) is a common problem among adolescents and young adults and has long-term consequences for the health and development of youth.</p><p><strong>Methods: </strong>Data on incidence and disability adjusted life years (DALYs) of IV (physical violence by firearm, by sharp object, sexual violence, and by other means) for adolescents and young adults aged 10-24 years in 204 countries and territories were retrieved from the GBD 2019. The age standardised rate (ASR) and estimated annual percentage change (EAPC) were used to analyze the global trends by sex, and SDI.</p><p><strong>Results: </strong>Globally, in 2019, the age-standardised incidence rate (ASIR) of IV among adolescents and young adults was 566.0 per 100,000 person years. From 1990 to 2019, the IV incidence and the age-standardised DALYs rate of IV among adolescents and young adults decreased globally. At the regional level, the largest increases in ASIR of IV from 1990 to 2019 were observed in Oceania (0.94%), Caribbean (0.81%), and Southern Latin America (0.63%). A reversed V-shaped association was found between the SDI and the burden of IV at the regional level.</p><p><strong>Conclusions: </strong>Unwavering efforts must be made to prevent IV among adolescents and young adults and care for victims of IV.</p><p><strong>Impact: </strong>Although the burden of IV is decreasing worldwide from 1990 to 2019, the most significant increase was found in Oceania, the Caribbean, and Latin America. High-income North America continues to be affected by physical violence by firearm, while East Asia continues to face issues with sexual violence. Unwavering efforts must be made to prevent IV among adolescents and young adults and care for victims of IV, including clinical and mental health.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence of probiotic sepsis and morbidity risk in premature infants: a meta-analysis.","authors":"Keith Feldman, Janelle R Noel-MacDonnell, Lucy B Pappas, Jermine Harriet Romald, Shelby L Olson, Alexandra Oschman, Alain C Cuna, Venkatesh Sampath","doi":"10.1038/s41390-025-04072-3","DOIUrl":"https://doi.org/10.1038/s41390-025-04072-3","url":null,"abstract":"<p><strong>Background: </strong>For preterm infants, supplementation with probiotics improves rates of necrotizing enterocolitis (NEC) and other morbidities. Case reports of probiotic sepsis have prompted warnings from the American Academy of Pediatrics and the Federal Drug Administration. However, incidence rates of probiotic sepsis are lacking, making it challenging to evaluate risk-benefit tradeoffs. We performed a meta-analysis and review of probiotic sepsis events in preterm infants to evaluate tradeoffs against NEC, mortality, and clinical sepsis outcomes.</p><p><strong>Methods: </strong>Dual-reviewers screened 160 articles, selecting 77 for review. Pooled estimates of incidence were computed using random-effect models. Case reports captured infant demographics, hospital course, and outcome.</p><p><strong>Results: </strong>For 20,323 exposed infants across 63 studies, 8 probiotic sepsis cases were identified [estimate: 0% (95% CI: 0-10%)]. Risk-benefit calculations note an additional 62 cases of NEC, 42 deaths, and 92 clinical sepsis events in the unexposed cohort per case of probiotic sepsis. Case reports identified 27 probiotic sepsis events, mostly in extremely-low-birthweight infants (median GA/BW: 28 weeks, 970.0 g) and those at risk for bacterial translocation.</p><p><strong>Conclusion: </strong>Probiotic sepsis is extremely rare in preterm infants, with the greatest risk in an identifiable sub-population. Estimates highlighted increased morbidities in unexposed cohorts compared to probiotic sepsis incidence, suggesting consideration of risk-benefit may be warranted.</p><p><strong>Impact: </strong>This study quantifies the risk of probiotic sepsis in preterm infants utilizing a meta-analysis. In over 20,000 exposed infants across 40 randomized trials and 23 observational studies, 8 cases of probiotic sepsis were identified (<0.04%). Assessing this risk against improvements in morbidities with probiotic use, we can expect 62 more cases of NEC, 42 more deaths, and 92 more cases of clinical sepsis per case of probiotic sepsis (1:2500) avoided in the unexposed group. While the use of probiotics carries risk, rates for probiotic sepsis presented by this analysis highlight a favorable benefit/risk ratio in preterm infants.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the effectiveness of elimination diet in infants with CMP-induced allergic proctocolitis using CoMiSS.","authors":"Menşure Nur Çelik, Eda Köksal, Sinem Polat Terece, Gizem Köken, Hacer İlbilge Ertoy Karagöl, Arzu Bakirtas","doi":"10.1038/s41390-025-04117-7","DOIUrl":"https://doi.org/10.1038/s41390-025-04117-7","url":null,"abstract":"<p><strong>Background: </strong>There are no data on using the Cow's Milk Protein Related Symptom Score (CoMiSS), a clinical screening tool, to monitor symptom improvement in infants with cow's milk protein allergy (CMPA). This study aimed to evaluate the efficacy of CoMiSS on elimination diet response in infants diagnosed with Cow's Milk Protein Associated Proctocolitis (CMPAP) compared with healthy controls METHODS: A case-control study with follow-up compared infants with CMPAP on an elimination diet to healthy peers. Infants with CMPAP (n = 13) and healthy infants (n = 22), aged 17-26 weeks, were included. Four visits were conducted at six, seven, nine, and 12 months of age. CoMiSS was assessed at each visit.</p><p><strong>Results: </strong>CoMiSS significantly decreased after the four-week elimination diet (p < 0.05). At study's end, total CoMiSS scores increased in both groups (p < 0.05). The crying score's median was higher in CMPAP infants than controls at Visits 1 and 3 (p < 0.05). No significant changes were found for other symptoms.</p><p><strong>Conclusions: </strong>CoMiSS tends to decrease during elimination diet in infants with CMPAP, which is promising for its use in evaluating dietary response. Monitoring the crying score and developing the defecation score specific to CMPAP would serve this purpose more.</p><p><strong>Impact: </strong>The CoMiSS can be a promising tool for monitoring responses to elimination diets in infants with proctocolitis, a specific subgroup of CMPA. It highlights the potential of CoMiSS to monitor dietary response and suggests refinements for its application, such as focusing on crying scores and developing a CMPA-specific defecation score. The findings pave the way for a novel use of CoMiSS beyond its screening purpose, potentially enhancing clinical management of CMPA in infants with proctocolitis. This approach could lead to more tailored and effective dietary interventions, improving patient outcomes and contributing to the refinement of CMPA management tools.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychosocial factors and the development of childhood overweight and obesity: a UK cohort study.","authors":"I Gusti Ngurah Edi Putra, Michael Daly, Eric Robinson","doi":"10.1038/s41390-025-04113-x","DOIUrl":"https://doi.org/10.1038/s41390-025-04113-x","url":null,"abstract":"<p><strong>Background: </strong>We examined the role of psychosocial factors in overweight and obesity development.</p><p><strong>Methods: </strong>UK Millennium Cohort Study data of children with normal weight at baseline were analysed. Weight changes were determined from baselines at ages 11 (n = 7979) and 14 (n = 6906) to follow-up at age 17. Baseline individual psychosocial factors were combined into two distinct indexes (caregiver-reported child mental health, child-reported psychosocial well-being). Regression models examined the associations between baseline indexes and individual psychosocial factors and overweight and obesity development (vs. no development) and body mass index (BMI) z-score changes.</p><p><strong>Results: </strong>Worse child mental health, but not psychosocial well-being, at age 11 was associated with overweight and obesity development (OR = 1.14; 95% CI = 1.02, 1.27) and increased BMI z-scores (β = 0.08; 95% CI = 0.04, 0.12) to age 17. No psychosocial indexes at age 14 predicted the outcomes. Further analyses showed that child mental health at ages 11 vs. 14 was more likely to predict the outcomes. Based on individual factors, externalising symptoms and experiencing peer bullying at age 11 may be important contributors to overweight and obesity development.</p><p><strong>Conclusions: </strong>Poor child mental health at age 11 is associated with overweight and obesity development by age 17. Late childhood/early adolescence may be a sensitive period in which psychosocial factors predict body weight trajectories.</p><p><strong>Impact: </strong>Worse psychosocial factors, particularly poor mental health, at ages 11, but not 14, were associated with overweight and obesity development and increased BMI z-scores by age 17. Late childhood/early adolescence may be a sensitive period for mental health in predicting future weight change. Future research will benefit from exploring this potential sensitive period and understanding potential mechanisms.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Equitable research is better research: let's invest in doing it right.","authors":"Shazeen Suleman, David Keller, Maya I Ragavan","doi":"10.1038/s41390-025-04119-5","DOIUrl":"https://doi.org/10.1038/s41390-025-04119-5","url":null,"abstract":"","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic analysis identifying proteins relevant for treatment success following experimental neonatal inflammation-sensitized hypoxia-ischemia.","authors":"Hannah Burkard, Damjan Osredkar, Elke Maes, Maria E Bernis, Anna-Sophie Bremer, Margit Zweyer, Paul Dowling, Kay Ohlendieck, Marianne Thoresen, Hemmen Sabir","doi":"10.1038/s41390-025-04097-8","DOIUrl":"https://doi.org/10.1038/s41390-025-04097-8","url":null,"abstract":"<p><strong>Background: </strong>Understanding the mechanisms of injury following neonatal hypoxic-ischemic encephalopathy (HIE) is a major goal in neonatal research. HIE can have severe effects on cognitive and motor development in newborns, including an increased risk of death. As the incidence is 10-20 times higher in low- and middle-income countries compared to developed countries, the interest in a therapy exists worldwide. Therapeutic hypothermia (HT) is the only effective treatment after HIE. However, TH is not universally effective, particularly in cases of inflammation-sensitized hypoxia-ischemia (HI); it provides limited benefit.</p><p><strong>Methods: </strong>To identify proteins that may contribute to the reduced efficacy of HT in the case of pre-HI inflammation sensitization, the proteomic profiles of animals subjected to HI and HT combined with lipopolysaccharide (LPS) were analyzed via liquid chromatography mass spectrometry (LC-MS/MS).</p><p><strong>Results: </strong>We identified proteins that potentially support the efficacy of HT and those that prevent the success of the therapy in the neonatal rat model of inflammation-sensitized HI.</p><p><strong>Conclusion: </strong>This study represents a step forward in identifying proteins related to the efficacy of HT following inflammation-sensitized HI.</p><p><strong>Impact: </strong>Therapeutic hypothermia is the only available treatment for neonatal hypoxic-ischemic encephalopathy, but not effective in models of inflammation-sensitized hypoxic-ischemic brain injury. Using liquid chromatography mass spectrometry, we identified proteins possibly having an effect on the treatment success of therapeutic hypothermia following experimental inflammation-sensitized hypoxic-ischemic brain injury. This proteomic analysis reveals proteins as potential markers that could prevent or support the efficacy of therapeutic hypothermia in experimental neonatal inflammation-sensitized hypoxic-ischemic encephalopathy.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}