Search Results (447)

(1) Background: The assessment of neonatal health and prognosis is one of the most critical areas in pediatric medicine. Intrauterine inflammation and the fetal inflammatory response syndrome (FIRS) are increasingly recognized as major determinants of neonatal morbidity. Interleukin-6 (IL-6), measured in the umbilical cord (UC) blood, has emerged as a promising biomarker, reflecting both intrauterine conditions and early neonatal risk. This narrative review aims to synthesize current evidence on the predictive value of umbilical cord blood IL-6 for neonatal outcome, including sepsis, respiratory distress, hypoxic–ischemic encephalopathy (HIE) and mortality. (2) Methods: A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science. Studies reporting umbilical cord IL-6 levels in relation to neonatal outcomes were analyzed and summarized narratively. (3) Results: Evidence consistently indicates that elevated umbilical cord IL-6 is associated with early-onset neonatal sepsis (EONS) and respiratory complications, and provides prognostic insight into neurological outcomes, even though results are influenced by gestational age (GA), mode of delivery, and the presence of chorioamnionitis. (4) Conclusions: UC IL-6 represents a valuable early biomarker for neonatal risk stratification and supports clinical decision-making. Future research should prioritize assay standardization, reference interval development, and prospective multicenter studies to validate its integration into routine neonatal care. Full article

Purinergic P2X7 receptors (P2X7Rs) may provide cardioprotection against ischemic heart disease. Cardiac angiogenesis is an endogenous adaptive response of hypoxic cardiomyocytes, mediated by vascular endothelial growth factor (VEGF) via hypoxia-inducible factor-1α (HIF-1α). The study aimed to determine whether P2X7Rs can regulate cardiac pro-angiogenic signaling in hypoxic H9c2 cardiomyocytes by modulating the angiogenic factor VEGF through HIF-1α genes. H9c2 rat cardiomyocytes were exposed to hypoxia alone or in combination with the P2X7R antagonist A740003. Subsequently, ATP levels and LDH activity were measured. The expression of P2X7R, HIF-1α, and VEGF was detected. Intracellular ATP level was significantly lower in hypoxia cardiomyocytes, whereas extracellular ATP, HIF-1α, and LDH levels were significantly higher in hypoxic cardiomyocytes. These effects were associated with increased P2X7R and VEGF gene expressions. Pretreatment with A740003 reversed HIF-1α and VEGF expressions in hypoxic cardiomyocytes. The findings suggest that P2X7Rs regulate pro-angiogenic signaling in hypoxic cardiomyocytes through the HIF-1α/VEGF pathway. Thus, the P2X7R-mediated HIF-1α/VEGF pathway may represent a novel approach to stimulating angiogenesis and preventing heart failure in ischemic heart disease. Full article

Ischemia/reperfusion injury (IRI) is a common damage due to the restoration of blood flow following an ischemic injury. Its pathogenesis is mainly linked to the production of reactive oxygen species (ROS), which sustain cell damage and promote cell death. The tardigrade damage suppressor protein (Dsup) is a DNA-binding protein that enables tardigrades to tolerate stress conditions, including oxidative stress. We investigated the ability of the Dsup to protect human cells from IRI, using an in vitro model of hypoxia and reoxygenation. We exposed HEK293TT cells transfected with the Dsup to hypoxic injury and analyzed cell viability, oxidative stress, expression of antioxidant proteins using functional assays, and a proteomic approach to dissect the molecular mechanisms modulated by the Dsup. Dsup expression significantly enhanced cell survival following hypoxia-reoxygenation and markedly reduced intracellular ROS levels. Proteomic and Western blot analyses revealed a significant upregulation of antioxidant enzymes in Dsup-expressing cells. Furthermore, the Dsup modulated autophagy and key stress-related pathways, including the MAPK cascade. This study demonstrates that the Dsup protects human cells from IRI by reducing oxidative stress and modulating key cytoprotective pathways. Our results establish the Dsup as a promising candidate for future therapeutic applications against IRI, meriting further exploration in in vivo models. Full article

Myocardial infarction (MI) remains a leading cause of mortality worldwide, yet effective cardioprotective strategies remain limited in clinical settings. Vascular endothelial growth factor B (VEGFB) has emerged as a promising therapeutic candidate in MI, but the role of its co-receptor, Neuropilin-1 (NRP1), in cardiomyocyte (CM) survival under ischemic stress remains poorly understood. Here, we investigated VEGFB-NRP1 signaling using an in vivo zebrafish model of cardiac injury as well as in vitro hypoxia models in CMs. We demonstrated that VEGFB overexpression conferred protection against ischemic injury and enhanced cardiac regeneration in the zebrafish heart. Mechanistically, we showed that VEGFB treatment enhances CM viability through reducing reactive oxygen species (ROS), ferroptosis activation, and preserving mitochondrial integrity. We also demonstrated that NRP1 knockdown in the CMs abolished the VEGFB-mediated protective effects, indicating the significant role of NRP1 signaling in VEGFB-induced cardioprotective effects in MI. Lastly, using transcriptome analysis, we confirmed that VEGFB induces anti-apoptotic and anti-ferroptosis gene programs in CMs in response to hypoxic stress. Collectively, our findings provide mechanistic insight into cell death activation pathways, including ferroptosis, in response to ischemic stress and further validate the therapeutic potential of VEGFB in promoting CM survival in ischemic heart disease. Full article

Background/Objectives: Sudden unexpected postnatal collapse (SUPC) is a rare but catastrophic event affecting apparently healthy neonates during the first days of life. Therapeutic hypothermia has been increasingly applied in this setting due to pathophysiological overlap with hypoxic–ischemic encephalopathy, but its effectiveness remains uncertain. The aim of this review is to systematically identify, appraise, and synthesize the evidence on therapeutic hypothermia for SUPC. Methods: We searched MEDLINE, Scopus, Embase, Web of Science, and Cochrane up to February 2025. Eligible studies included term or near-term infants with SUPC within seven days of life who underwent therapeutic hypothermia. Data were extracted on demographics, collapse circumstances, therapeutic hypothermia protocol, mortality, seizures, neuroimaging, and neurodevelopment. Results: Thirteen studies were included, encompassing 70 infants. Most events occurred within two hours of life, during skin-to-skin or breastfeeding, and were strongly associated with primiparity. Therapeutic hypothermia was typically initiated within six hours of collapse, using whole-body cooling at 33–34 °C for 72 h. Mortality was approximately 10% (widely ranging from 0 to 50%). Seizures were frequent (70–90%), and MRI abnormalities were reported in about half of cases. Approximately half of survivors demonstrated normal neurodevelopment at one year. Study quality was low to moderate, and risk of bias substantial. Conclusions: Therapeutic hypothermia is feasible in SUPC and survival with favorable outcomes has been documented, but the certainty of evidence is very low. Given recurrent risk factors such as primiparity and early skin-to-skin/breastfeeding, enhanced vigilance and preventive strategies are essential. Therapeutic hypothermia should be considered case by case, ideally within specialized centers and supported by registries. Full article

Despite significant progress in preclinical research aimed at developing effective therapies for the acute and long-term consequences of perinatal asphyxia, there is still a lack of clinical protocols to regenerate the neonatal brain damaged by hypoxic-ischemic (HI) injury. To date, only therapeutic hypothermia is routinely used in neonates who have experienced perinatal asphyxia. It has been shown to be effective only in limiting the spread of brain damage caused by a cascade of molecular and biochemical events triggered by limited blood supply to the body’s organs, including the fragile, developing brain. Ongoing clinical trials are exploring pharmacological approaches aimed at promoting neurogenesis and gliogenesis to repair damaged neural tissue, as well as modulating the neuroinflammation that results from the cellular response to HI injury. Among promising therapeutic agents, erythropoietin, and melatonin have emerged as major drugs with potential neuroprotective effects in neonatal hypoxic-ischemic encephalopathy. Erythropoietin is recognized for its anti-apoptotic, anti-oxidative, and anti-inflammatory properties, supporting neural cell survival and regeneration. Melatonin acts as a potent antioxidant and anti-inflammatory agent, helping to reduce oxidative stress and inflammation triggered by HI injury. As clinical trials on suffering neonates are highly demanding, the ethical and practical concerns of therapeutic approaches are discussed. An urgent need to develop a safe, feasible, and effective clinical approach to promote the restoration of appropriate neurodevelopment in the near future is highlighted. This review summarizes the clinical trials conducted to date, discusses their outcomes and limitations, and considers translational potential of the tested treatment strategies. Full article

Novel coronavirus (SARS-CoV-2) is highly infectious and pathogenic. Novel coronavirus infection can not only cause respiratory diseases but also lead to multiple organ damage through direct or indirect mechanisms, in which the liver is one of the most frequently affected organs. It has been reported that 15–65% of coronavirus disease 2019 (COVID-19) patients experience liver dysfunction, mainly manifested as mild to moderate elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Severe patients may progress to liver failure, develop hepatic encephalopathy, or have poor coagulation function. The mechanisms underlying this type of liver injury are complex. Pathways—including direct viral infection (via ACE2 receptors), immune-mediated responses (e.g., cytokine storm), ischemic/hypoxic liver damage, thrombosis, oxidative stress, neutrophil extracellular trap formation (NETosis), and the gut–liver axis—remain largely speculative and lack robust clinical causal evidence. In contrast, drug-induced liver injury (DILI) has been established as a well-defined causative factor using the Roussel Uclaf Causality Assessment Method (RUCAM). Treatment should simultaneously consider antiviral therapy and liver protection therapy. This article systematically reviewed the mechanism, clinical diagnosis, treatment, and management strategies of COVID-19-related liver injury and discussed the limitations of current research and the future directions, hoping to provide help for the diagnosis and treatment of such patients. Full article

Background and Objectives: Neuron-specific enolase (NSE) is an isoenzyme of enolase, of which the γ isoform is expressed in nerve cells. The activity of NSE occurs during late neuronal differentiation, which determines the specificity of the enzyme for neurodevelopmental cells. The activity of NSE is also observed in processes associated with neuronal damage. The aim of this study was to present the state of the art related to the knowledge, advances, and possible developmental directions in terms of the use of NSE as a biomarker in the diagnosis of selected neurological and mental disorders (NDs, MDs), with particular emphasis on ischemic stroke (IS) and psychotic disorders (PSDs). Materials and Methods: A literature review was performed using the PubMed, Embase, and Scopus databases. Keywords such as “neuron-specific enolase”, “neuron-specific enolase in schizophrenia”, “neuron-specific enolase in ischemic stroke”, “neuron-specific enolase in psychiatric disorders”, and “neuron-specific enolase in neurological diseases” were used during the literature search. A total of 11,350 items were found. However, 188 papers were finally selected after applying the filters (“clinical trial”, “meta-analysis”, “randomized control trial”, and “systematic review”). Results: The literature was analyzed and 67 items relevant to the subject of this study were selected. This article points out the differences in NSE levels in different clinical groups, such as patients after an incident of hypoxic/ischemic encephalopathy (HIE), neuroinfection, or particular inflammatory processes in the nervous system region, as well as central nervous system (CNS) injury, selected MD, neurodegenerative disorders (NGDs), headaches, or epilepsy (EP). Conclusions: In the future, they may serve to support further work on the use of enolase as a potential biomarker of the described diseases. Full article

Background: Incarcerated patients with neurological complaints present substantial diagnostic and care-delivery challenges in emergency departments (EDs). We delineate the clinical spectrum, severity, and outcomes among incarcerated patients managed in an ED with an embedded neuro-emergency expert model. Methods: A retrospective observational study of adult ED visits for neurological symptoms was conducted from September 2018 to June 2025 at a government-designated regional emergency center serving multiple correctional facilities. Incarceration was confirmed in the electronic medical record. Extracted variables included demographics, chief complaint, comorbidities, triage and acuity scale, Glasgow Coma Scale (GCS), neuroimaging, ED diagnoses, and outcomes (hospital admission, ICU care, ED/in-hospital mortality). Results: Sixty-five patients were included (median age 57.0 years [IQR 47.0–64.5]; 95% male). Chief complaints were altered mental status (36.9%), hemiparesis (21.5%), and seizures (13.8%). On arrival, 40.0% had GCS ≤ 12, including 23.1% with severe impairment (GCS 3–8). Non-contrast head CT was obtained in 95.4% and diffusion-weighted MRI in 38.5%. Frequent diagnoses were psychiatric/functional neurological disorder (16.9%), metabolic encephalopathy (15.4%), and acute ischemic stroke (12.3%). Serious conditions (stroke, hypoxic brain injury, central nervous system infection, status epilepticus, and neuroleptic malignant syndrome) were diagnosed in 41.5%. Hospital admission occurred in 63.1% (ICU care in 47.7%); in-hospital mortality was 10.8%. Conclusions: ED visits by incarcerated individuals with neurological complaints were often linked to serious diagnoses, ICU use, and mortality, challenging assumptions of exaggeration. Over two in five had stroke, hypoxic brain injury, central nervous system infection, or status epilepticus. The findings support rapid, systematic, bias-aware evaluation with early neurological involvement, clear imaging triggers, safety protocol, and expedited transfers from correctional facilities. Full article

Background: Out-of-hospital cardiac arrest (OHCA) survivors demonstrate wide variation in neurological outcomes due to hypoxic–ischemic brain injury. Early prognostic stratification in the emergency department is essential to inform clinical decisions. This study aimed to improve the revised Cardiac Arrest Syndrome for Therapeutic hypothermia (rCAST) score by incorporating additional clinical variables and to evaluate its ability to predict poor neurological outcomes. Methods: This multicenter observational study analyzed OHCA survivors treated with targeted temperature management (TTM) between October 2015 and December 2018 at 22 university-affiliated hospitals participating in the Korean Hypothermia Network prospective registry. The primary outcome was poor neurological status at one month, defined as a Cerebral Performance Category (CPC) score of 3–5. Independent predictors were identified using multivariable logistic regression and incorporated into a modified rCAST (mCAST) score. Results: Among 881 included patients, age > 65 years (odds ratio [OR], 13.87; 95% confidence interval [CI], 7.38–26.08) and absence of brainstem reflexes (OR, 2.31; 95% CI, 1.29–4.12) were identified as independent predictors and added to the mCAST score. The mCAST demonstrated higher prognostic accuracy than the original rCAST (area under the curve [AUC], 0.849 vs. 0.823; p < 0.001). In the high-severity group, the mCAST identified a higher poor outcome rate (95.1% vs. 90.9%) while reducing the proportion of patients in this group (20.7% vs. 31.3%). Conclusions: The mCAST score improves early prognostic accuracy during the immediate post-cardiac arrest period by incorporating age and brainstem reflexes and may offer refined risk stratification without compromising clinical feasibility. Full article

This review explores the maternal gut microbiome’s role in shaping neonatal neurodevelopmental outcomes following perinatal asphyxia (PA), a leading cause of infant mortality and disability with limited therapeutic options beyond hypothermia. We synthesized current evidence on microbiome-mediated neuroprotective mechanisms against hypoxic-ischemic brain injury. The maternal microbiome influences fetal development through bioactive metabolites (short-chain fatty acids, indole derivatives) that cross the placental barrier, bacterial antigen regulation, and infant microbiome colonization. These pathways activate multiple protective mechanisms: anti-inflammatory signaling via NF-κB suppression and regulatory T cell expansion; antioxidant defenses through Nrf2 activation; neural repair via BDNF upregulation and neurogenesis; and oxytocin system modulation. Animal models demonstrate that maternal dysbiosis from high-fat diet or antibiotics exacerbates PA-induced brain damage, increasing inflammatory markers and hippocampal injury. Conversely, probiotic supplementation, dietary fiber, and specific interventions (omega-3, resveratrol) reduce neuroinflammation and oxidative injury. Human studies link maternal dysbiosis-associated conditions (obesity, gestational diabetes) with adverse pregnancy outcomes, though direct clinical evidence for PA severity remains limited. Understanding the maternal microbiome-fetal brain axis opens therapeutic avenues, including prenatal probiotics, dietary modifications, and targeted metabolite supplementation to prevent or mitigate PA-related neurological sequelae, potentially complementing existing neuroprotective strategies. Full article

The prevalence of hypoxia-caused eye diseases is increasing, but effective, non-invasive treatment options are not available. Abscisic acid (ABA) is a plant hormone with anti-inflammatory and antioxidant effects. ABA is also present in various mammalian tissues and plays an important role in metabolic processes. Therefore, we aimed to investigate the potential protective role of ABA eye drops in ischemic retinopathy. Retinal ischemia was induced by permanent unilateral common carotid artery occlusion (UCCAO) in mice. Half of the animals received ABA eye drops two times a day for two weeks. Optical coherence tomography (OCT) was used to follow the changes in retinal thickness. Moreover, immunohistochemistry and molecular biology methods were used to explore the morphological changes and the underlying mechanisms, respectively. Based on OCT measurements, ischemic retinopathy was successfully developed. The decrease in the thickness of numerous retinal layers could be prevented with ABA eye drops. The ganglion cell number decreased significantly after UCCAO in the central and peripheral regions of the retina. ABA treatment could moderate the damage in both regions. Furthermore, our apoptosis array results suggest that ABA regulates the apoptotic pathways under hypoxic conditions. In conclusion, ABA eye drops may represent a new potential therapeutic option for the treatment of ischemic retinopathy. Full article

Background and Objectives: Neonates with moderate-to-severe hypoxic–ischemic encephalopathy (HIE) in low- and middle-income countries (LMICs) remain at high risk of neurological sequelae despite access to therapeutic hypothermia (TH). Real-time accessible biomarkers are required to improve risk stratification and guide neuroprotective care in these settings. This study evaluated the predictive capacity of heart rate variability (HRV) metrics for brain injury detected using magnetic resonance imaging (MRI) in neonates with HIE who underwent TH at an LMIC. Materials and Methods: We conducted a prospective observational study of 87 neonates treated with TH in a tertiary neonatal intensive care unit in Colombia. HRV was recorded during the first 24 h of TH, during rewarming, and 24 h after rewarming. Brain MRI was performed within the first week of life and scored using the Rutherford system. Associations between HRV metrics and global and regional brain injuries were analyzed using receiver operating characteristic (ROC) curves and multivariable logistic regression models. Results: Low-frequency (LF) and high-frequency (HF) powers were significantly lower in neonates with MRI abnormalities. LF power during rewarming demonstrated the highest predictive accuracy (AUC = 0.90), followed by HF power during the first 24 h (AUC = 0.80). Region-specific analyses showed that LF power reduction was significantly associated with white matter and basal ganglia injury. Conclusions: HRV, particularly LF power during rewarming, is a promising and accessible biomarker for regional brain injury in neonates with perinatal asphyxia treated with TH. Full article

Background: This study examined the effects of repeated ischemic preconditioning (IPC) combined with normobaric hypoxia on anaerobic performance and physiological stress markers. Methods: Fourteen physically active males (22.3 ± 3.1 years) completed three randomized, single-blind crossover sessions under the following conditions: (1) normoxia (NOR), (2) normobaric hypoxia (HYP; FiO₂ = 14.7%), and (3) hypoxia with IPC (IPC-HYP). Each session included three 30 s cycling Wingate tests separated by four minutes of passive recovery. Blood samples were collected pre-exercise, immediately post-exercise, and 15 min post-exercise to assess lactate, pH, bicarbonate (HCO₃⁻), and creatine kinase (CK) activity. Results: Peak power output was highest under NOR during Wingate II and III. IPC-HYP attenuated the decline in peak power compared to that under HYP (e.g., Wingate II: 15.56 vs. 12.52 W/kg). IPC-HYP induced greater lactate accumulation (peak: 15.45 mmol/L, p < 0.01), more pronounced acidosis (pH: 7.18 post-exercise), and lower bicarbonate (9.9 mmol/L, p < 0.01). CK activity, measured immediately and then 1 h and 24 h post-exercise, was highest under IPC-HYP at 24 h (568.5 U/L). Conclusions: IPC-HYP mitigates the decline in peak anaerobic power observed under hypoxia, despite eliciting greater metabolic and muscular stress. These findings suggest that IPC may enhance physiological adaptation to hypoxic training, potentially improving anaerobic performance. Full article

Background: Fetal size is often dichotomized as normal or abnormal using the 10th percentile of estimated fetal weight (EFW) or abdominal circumference as a cutoff. While the risk of adverse perinatal outcomes decreases with increasing fetal weight percentile, no percentile completely eliminates that risk. Objective: The aim of this study was to compare perinatal outcomes between fetuses with an EFW between the 10th and 20th percentiles and those with an EFW between the 20th and 90th percentiles (i.e., >20 and <90) at the beginning of the accelerated growth stage (28.0–30.0 weeks’ gestation). Methods: We conducted a retrospective cohort study of singleton pregnancies managed at a quaternary center in Mexico City (2017–2024). Outcomes were compared based on EFW percentiles at 28.0–30.0 weeks. The primary outcome was adverse neonatal outcome (ANeO), defined as the presence of at least one of the following: umbilical artery pH ≤ 7.1, 5 min Apgar ≤ 7, NICU admission, early neonatal hypoglycemia, non-reassuring fetal status, respiratory distress syndrome, intraventricular hemorrhage, hypoxic–ischemic encephalopathy, or perinatal death. Secondary outcomes included progression to fetal growth restriction (FGR) and low birth weight. Modified Poisson regression was used to estimate adjusted risk ratios (aRRs) with 95% confidence intervals (CIs). Results: Among 650 cases, ANeO occurred in 45.8% of fetuses in the 10th–20th percentile group vs. 29.4% in the 20th–90th percentile group (aRR: 1.51, 95% CI: 1.22–1.86; p < 0.001). FGR and low birth weight were also more frequent in the 10th–20th percentile group (21.1% and 27.6% vs. 6.4% and 5.8%, respectively; p < 0.001). Conclusions: Fetuses between the 10th and 20th percentiles at 28–30 weeks have increased risks of neonatal morbidity, FGR, and low birth weight. Full article