A novel HDAC8 inhibitor H7E exerts retinoprotective effects against glaucomatous injury via ameliorating aberrant Müller glia activation and oxidative stress.

Glaucoma is considered a neurodegenerative disease characterized by progressive visual field defects that may lead to blindness. Although controlling intraocular pressure (IOP) is the mainstay of glaucoma treatment, some glaucoma patients have unmet needs due to unclear pathogenic mechanisms. Recently, there has been growing evidence that neuroinflammation is a potential target for the development of novel antiglaucoma agents. In this study, we investigated the protective effects and cellular mechanisms of H7E, a novel small molecule inhibits HDAC8, using in vitro and in vivo glaucoma-like models. Importantly, H7E mitigated extracellular MMP-9 activity and MCP-1 levels in glutamate- or S100B-stimulated reactive Müller glia. In addition, H7E inhibited the upregulation of inflammation- and proliferation-related signaling pathways, particularly the ERK and JNK MAPK pathways. Under conditions of oxidative damage, H7E prevents retinal cell death and reduces extracellular glutamate released from stressed Müller glia. In a mouse model of NMDA-induced retinal degeneration, H7E alleviated functional and structural defects within the inner retina as assessed by electroretinography and optical coherence tomography. Our results demonstrated that the newly identified compound H7E protects against glaucoma damage by specifically targeting HDAC8 activity in the retina. This protective effect is attributed to the inhibition of Müller glial activation and the prevention of retinal cell death caused by oxidative stress.

Comparison of propofol and desflurane for postoperative neurocognitive function in patients with aneurysmal subarachnoid hemorrhage: A prospective randomized trial.

Background: Following aneurysmal subarachnoid hemorrhage, 40-50% of survivors experience cognitive dysfunction, which affects their quality of life. Anesthetic agents play a pivotal role in aneurysm surgeries. However, substantial evidence regarding their effects on neurocognitive function is lacking. This study evaluated the effects of propofol and desflurane on postoperative neurocognitive function and serum S-100B levels. Methods: One hundred patients were equally randomized to receive either propofol (Group P) or desflurane (Group D). Cognitive function was assessed using the Montreal Cognitive Assessment scale at three different time points: Preoperatively, at the time of discharge, and one month after surgery. Perioperative serum levels of S-100B were also measured. Results: The preoperative mean cognitive score in Group P was 21.64 + 4.46 and in Group D was 21.66 + 4.07 (P = 0.79). At discharge, a significant decrease in cognitive scores was observed compared to preoperative scores (Group P- 20.91 + 3.94, P = 0.03 and Group D-19.28 + 4.22, P = 0.00); however, scores were comparable between the two groups (P = 0.09). One month following surgery, mean cognitive scores were 22.63 + 3.57 in Group P and 20.74 + 3.89 in Group D, and the difference was significant (P = 0.04). Higher memory and orientation scores were observed in Group P than in Group D at one month (P < 0.05) in the subgroup analysis. Both groups had similar serum S-100B levels. Conclusion: The mean cognitive scores one month after surgery improved significantly with propofol compared with desflurane, but without clinical significance. Individual domain analysis demonstrated that orientation and memory scores were better preserved with propofol.

Clinical value of serum LINC02446 and S100B in early diagnosis and prognosis assessment of traumatic brain injury.

OBJECTIVE: To detect the expression levels of LINC02446 and S100B in serum of patients with traumatic brain injury (TBI) and explore their values as diagnostic and prognostic indicators for TBI. METHOD: Abnormal expressed RNAs in brain injury were screened from the dataset GSE1131475. Serums were collected from moderate to severe TBI patients at 1-3 and 4-12 h post injury. Quantitative polymerase chain reaction was used to detect the expression levels of LINC02446 and S100B in serum. The Glasgow Outcome Scale was used for prognostic evaluation. The diagnostic and prognostic efficacy of LINC02446 and S100B in TBI was evaluated using the receiver operating characteristic (ROC) curve. RESULT: The serum expression levels of LINC02446 and S100B in the TBI group were significantly increased. The expression levels of LINC02446 and S100B in the severe TBI group were significantly higher than those in the mild TBI group. ROC curve analysis showed that the combination of LINC02446 and S100B can distinguish TBI patients from healthy controls, as well as mild TBI from moderate to severe TBI. At the 6-month follow-up, the expression levels of LINC02446 and S100B in TBI patients with poor prognosis were significantly higher than those in patients with good prognosis, and ROC results showed their differentiation value. Moreover, the expression level of LINC02446 at 0-3 h can serve as an independent prognostic factor for poor prognosis. CONCLUSION: Serum LINC02446 and S100B hold clinical application value in the diagnosis and prognosis of TBI and are expected to become new potential biomarkers.

A Prospective Study on Neural Biomarkers in Patients with Long-COVID Symptoms.

BACKGROUND: this prospective observational study aims to assess serum levels of glial fibrillary acidic protein (GFAP), s100b, and total Tau in long-COVID patients, exploring correlations with symptoms, cognitive decline, mental health, and quality of life. METHODS: Long-COVID patients visiting our outpatient clinic (February 2021-December 2022) were screened alongside age- and sex-matched controls. GFAP, s100b, and total Tau in serum were measured with ELISA. Cognitive function, depression, anxiety, post-traumatic stress disorder, and quality of life were evaluated using MoCA, HADS (depression and anxiety), IES-R, and SF-36, respectively. RESULTS: Sixty-five long-COVID patients and 20 controls were included. GFAP levels were significantly higher in long-COVID patients (p = 0.031), though not correlating with the presence of long-COVID symptoms. S100b and total Tau showed no significant differences between patients and controls. Nervous system-related symptoms were reported in 47% of patients. High rates of cognitive decline (65.9%), depression (32.2%), anxiety (47.5%), and post-traumatic stress disorder (44.1%) were observed. Over 80% of the study population scored below normative cutoffs for SF-36, indicating a significant impact on quality of life. CONCLUSIONS: in this long-COVID cohort with substantial psychological and cognitive symptoms, GFAP levels were elevated compared to controls, though not correlating with the presence of long-COVID symptoms.

Serum S100B protein and white matter changes in schizophrenia before and after medication.

Schizophrenia patients have abnormalities in white matter (WM) integrity in brain regions. S100B has been shown to be a marker protein for glial cells. The atypical antipsychotics have neuroprotective effects on the brain. It is not clear whether antipsychotics can induce S100B changes and improve symptoms by protecting oligodendrocytes. To investigate WM and S100B changes and associations and determine the effect of quetiapine on WM and S100B in schizophrenia patients, we determined serum S100B levels with solid phase immunochromatography and fractional anisotropy（FA）values of 36 patients and 40 healthy controls. Patients exhibited significantly higher serum concentrations of S100B and decreased FA values in left postcentral，right superior frontal，right thalamus, and left inferior occipital gyrus, while higher in right temporal cortex WM compared with healthy controls. Following treatment with quetiapine, patients had decreased S100B and higher FA values in right cerebellum，right superior frontal，right thalamus, and left parietal cortex，and decreased FA values in right temporal cortex WM compared with pre-treatment values. Furthermore, S100B were negatively correlated with PANSS positive scores and positively correlated with FA values in the left postcentral cortex. In addition，the percentage change in FA values in the right temporal cortex was positively correlated with the percentage change in the S100B, percentage reduction in PANSS scores, and percentage reduction in PANSS-positive scores. Our findings demonstrated abnormalities in S100B and WM microstructure in patients with schizophrenia. These abnormalities may be partly reversed by quetiapine treatment.

Correlation analysis between the amniotic fluid contamination and clinical grading of neonatal hypoxic-ischemic encephalopathy and biomarkers of brain damage.

BACKGROUND: Amniotic fluid contamination (AFC) is a risk factor for neonatal hypoxic ischemic encephalopathy (HIE); however, the correlation between AFC level and the incidence and clinical grading of HIE, in addition to relevant biomarkers of brain damage, have not been assessed. METHODS: This single-center observational study included 75 neonates with moderate-to-severe HIE. The neonates with HIE were divided into four subgroups according to the AFC level: normal amniotic fluid with HIE group (NAF-HIE), I°AFC with HIE group (I°AFC-HIE), II°AFC with HIE group (II°AFC-HIE), and III°AFC with HIE group (III°AFC-HIE). The control groups consisted of 35 healthy neonates. The clinical grading of neonatal HIE was performed according to the criteria of Sarnat and Sarnat. Serum tau protein and S100B were detected by enzyme-linked immunosorbent assay kits. Correlations of serum tau protein and S100B were evaluated using the Pearson correlation analysis. RESULTS: (1) The incidence of neonatal HIE in the NAF-HIE group was 20 cases (26. 7%), I°AFC-HIE was 13 cases (17.3%), II°AFC-HIE was 10 cases (13.3%), and III°AFC-HIE was 32 cases (42. 7%). The incidence of moderate-to-severe HIE in the I°-III°AFC-HIE groups was 73.3% (55/75). (2) In 44 cases with severe HIE, 26 cases (59.1%) occurred in the III°AFC-HIE group, which had a significantly higher incidence of severe HIE than moderate HIE (p < 0.05). In NAF-HIE and I°AFC-HIE groups, the incidence of moderate HIE was 45.2% and 29.0%, respectively, which was higher than that of severe HIE (X2 = 9.2425, p < 0.05; X2 = 5.0472, p < 0.05, respectively). (3) Serum tau protein and S100B levels in the HIE groups were significantly higher than in the control group (all p < 0.05), and were significantly higher in the III°AFC-HIE group than in the NAF-HIE and I°AFC-HIE groups (all p < 0.05). (4) Serum tau protein and S100B levels in the severe HIE group were significantly higher in the moderate HIE group (all p < 0.05). (5) Serum tau protein and S100B levels were significantly positively correlated (r = 0.7703, p < 0.0001). CONCLUSION: Among children with severe HIE, the incidence of III°AFC was higher, and the levels of serum tau protein and S100B were increased. AFC level might be associated with HIE grading.

Correlation Study on the Prognostic Value of miR-21 and S-100B Protein Levels in Neonatal Hypoxic-Ischemic Encephalopathy Undergoing Hypothermia Therapy.

OBJECTIVE: To evaluate the variations in serum levels of microRNA-21 (miR-21) and S-100B protein in neonates with hypoxic-ischemic encephalopathy (HIE) after receiving hypothermia therapy and explore the correlation of these biomarkers with the neurodevelopmental prognosis of the infants. METHODS: This retrospective analysis included 90 neonatal HIE patients diagnosed and treated between January 2019 and December 2022. Real-time quantitative PCR and enzyme-linked immunosorbent assay (ELISA) methods were used to measure miR-21 and S-100B protein levels. Neurodevelopmental assessments were conducted at one year, and follow-up was performed using the Bayley Scales of Infant and Toddler Development third edition. Statistical analysis was carried out using SPSS software, with t-tests for continuous variables, chi-square tests for categorical data, Pearson correlation coefficient for correlation analysis, and multivariate regression analysis to adjust for confounding factors. RESULTS: After hypothermia therapy, the observation group showed a significant decrease in miR-21 and S-100B protein levels (P < 0.001), and neurodevelopmental scores were significantly higher than the control group (P < 0.05). Correlation analysis indicated a negative correlation between miR-21 and neurodevelopmental scores (r=-0.62, P < 0.001), as well as a negative correlation between S-100B protein levels (r=-0.76, P < 0.001). Multivariate regression analysis demonstrated that miR-21 levels and S-100B protein levels maintained independent negative correlations with neurodevelopmental scores (P < 0.001). CONCLUSION: Hypothermia therapy significantly reduces serum levels of miR-21 and S-100B protein in neonatal HIE patients and may be associated with better prognosis. miR-21 and S-100B serve as prognostic biomarkers, aiding in predicting and improving the treatment outcomes and long-term prognosis of neonatal HIE.

1,25(OH)2D3 supplementation alleviates gut-vascular barrier disruption via inhibition of S100B/ADAM10 pathway.

Gut-vascular barrier (GVB) is the second barrier in mucosa to control systemic dissemination of gut bacteria. Severe burns induce enteroglial cells to produce S100B and endothelial cells to generate ADAM10 and cause vitamin D3 insufficiency/deficiency and GVB disruption. It is not clear whether vitamin D3 supplementation attenuates GVB damage via regulation of S100B/ADAM10 pathway. Here, GVB disruption was induced by 30% of total body surface area scalds. Rats were treated with 1,25(OH)2D3 (0.05, 0.5 or 5 µg/kg) or S100B monoclonal antibody (S100BmAb, 10 µg/kg) or GI254023X (ADAM10 inhibitor, 100 mg/kg). Rat enteric glial cell-line CRL2690 and rat intestinal microvascular endothelial cells (RIMECs) were treated with S100B (5 µM) or plus 1,25(OH)2D3 (0.05, 0.5 or 5 µM) or GI254023X (5 µM). S100B, TNF-α, 25(OH)D3 and 1,25(OH)2D3 in serum and gut mucosa were determined by enzyme-linked immunosorbent assay. The endothelial permeability was measured using FITC-dextran 70 kDa. ADAM10 and ß-catenin expression was assayed by Western blot. The results showed that 1,25(OH)2D3 and 25(OH)D3 concentration in serum reduced whereas TNF-α and S100B in serum and gut mucosa increased in burned rats. S100BmAb, GI254023X and 1,25(OH)2D3 treatment lowered burns-increased GVB permeability. 1,25(OH)2D3 also decreased S100B concentration in serum and gut mucosa. 1,25(OH)2D3 inhibited S100B release from TNF-α-treated CRL2690 and raised ß-catenin while decreasing ADAM10 protein in S100B-treated RIMECs. 1,25(OH)2D3 and GI254023X also decreased the endothelial permeability of S100B-treated RIMECs. Collectively, these findings provide evidence that severe burns lower serum 25(OH)D3 and 1,25(OH)2D3 concentration. 1,25(OH)2D3 supplementation alleviates burns-elicited GVB disruption via inhibition of S100B/ADAM10 signaling.

Combining biomarkers of BNIP3 L, S100B, NSE, and accessible measures to predict sepsis-associated encephalopathy: a prospective observational study.

BACKGROUND: Accurate identification of delirium in sepsis patients is crucial for guiding clinical diagnosis and treatment. However, there are no accurate biomarkers and indicators at present. We aimed to identify which combinations of cognitive impairment-related biomarkers and other easily accessible assessments best predict delirium in sepsis patients. METHODS: One hundred and one sepsis patients were enrolled in a prospective study cohort. S100B, NSE, and BNIP3 L biomarkers were detected in plasma and cerebrospinal fluid and patients' optic nerve sheath diameter (ONSD). The optimal biomarkers identified by Logistic regression are combined with other factors such as ONSD to filter out the perfect model to predict delirium in sepsis patients through Logistic regression, Naïve Bayes, decision tree, and neural network models. MAIN RESULTS: Among all biomarkers, compared with BNIP3 L (AUC = .706, 95% CI = .597-.815) and NSE (AUC = .711, 95% CI = .609-.813) in cerebrospinal fluid, plasma S100B (AUC = .729, 95% CI = .626-.832) had the best discrimination performance for delirium in sepsis patients. Logistic regression analysis showed that the combination of cerebrospinal fluid BNIP3 L with plasma S100B, ONSD, neutrophils, and age provided the best discrimination to cognitive impairment in sepsis patients (accuracy = .901, specificity = .923, sensitivity = .911), which was better than Naïve Bayes, decision tree, and neural network models. Neutrophils, ONSD, and cerebrospinal fluid BNIP3 L were consistently the major contributors in a few models. CONCLUSIONS: The logistic regression showed that the combination model was strongly correlated with cognitive dysfunction in sepsis patients.

Concentrations of S100B and neurofilament light chain in blood as biomarkers for checkpoint inhibitor-induced CNS inflammation.

BACKGROUND: Cancer treatment with immune checkpoint inhibition (ICI) can cause immune-related adverse events in the central nervous system (CNS irAE). There are no blood biomarkers to detect CNS irAE. We investigated if concentrations of S100-calcium-binding protein B (S100B) and neurofilament light chain (NfL) in blood can be used as biomarkers for CNS irAE and assessed the incidence of CNS irAE in a cohort of ICI-treated patients. METHODS: In this single-centre, retrospective cohort study, we examined medical records and laboratory data of 197 consecutive patients treated with combined CTLA-4 and PD-1 inhibition (ipilimumab; ipi + nivolumab; nivo) for metastatic melanoma or renal cell carcinoma. CNS irAE was diagnosed using established criteria. Concentrations of S100B and NfL in blood were measured in patients with CNS irAE and in 84 patients without CNS irAE. FINDINGS: Nine of 197 patients (4.6%) fulfilled criteria for CNS irAE. S100B and NfL in blood increased during CNS inflammation and normalized during immunosuppression. CNS irAE was detected with a sensitivity of 100% (S100B) and 79% (NfL) and a specificity of 89% (S100B) and 74% (NfL). Patients with CNS irAE had simultaneous increased concentration of C-reactive protein (CRP) (9/9) and alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) in blood (8/9). INTERPRETATION: Analysis of S100B, NfL and CRP in blood facilitates the diagnosis of CNS irAE. CNS irAE may be more common than previously reported. There may be shared immune mechanisms between CNS and hepatitis irAE. FUNDING: Supported by funding from the Swedish Cancer Foundation, the ALF-agreement, and Jubileumsklinikens Cancerfond.

Neurodesarrollo a los 2 años en cardiopatía congénita: utilidad pronóstica de los marcadores de daño cerebral / Neurodevelopmental outcomes in congenital heart disease: Usefulness of biomarkers of brain injury

Introducción: En la actualidad, las alteraciones del neurodesarrollo son la complicación más frecuente en los pacientes con cardiopatía congénita (CC) en edad escolar. Analizamos la incidencia de eventos neurológicos agudos (ENA) en pacientes con CC sometidos a cirugía cardiaca y la utilidad de los neuromarcadores para predecir el neurodesarrollo. Métodos: Estudio prospectivo observacional en recién nacidos (RN) con CC diagnosticada prenatalmente, y sometidos a cirugía el primer año de vida. Se evaluaron: 1) biomarcadores sanguíneos de lesión cerebral (S100B, enolasa neuronal específica) en sangre de cordón y periquirúrgicos; 2) datos clínicos y analíticos perinatales y periquirúrgicos; 3) tratamientos y complicaciones, y 4) neurodesarrollo (escala de Bayley III) a los 2 años. Resultados: Se incluyeron 84 RN con CC de diagnóstico fetal, confirmada posnatalmente, sometidos a cirugía cardiaca en el primer año de vida. Diecisiete pacientes tenían corazón univentricular, 20 pacientes obstrucción izquierda y 10 síndromes genéticos. Fallecieron en el periodo posquirúrgico 5 pacientes (5,9%) y 9 pacientes presentaron ENA (10,7%). Las puntuaciones medias en el test de Bayley III fueron normales, pero el 31% tuvieron alteración cognitiva, motora o en el lenguaje. Los pacientes con síndromes genéticos, ENA y CC univentriculares tuvieron peor neurodesarrollo. La elevación de S100B en el postoperatorio inmediato se correlacionó con peores puntuaciones. Conclusiones: Los pacientes con CC sometidos a cirugía tienen mayor riesgo de sufrir alteraciones del neurodesarrollo. Los pacientes con síndromes genéticos o corazones univentriculares presentan peores resultados. Presentar ENA posquirúrgico puede contribuir a peores resultados. Niveles de S100B elevados en el postoperatorio se correlacionan con peores resultados en los test de neurodesarrollo a los 2 años...(AU)

Introduction: At present, neurodevelopmental abnormalities are the most frequent type of complication in school-aged children with congenital heart disease (CHD). We analysed the incidence of acute neurologic events (ANEs) in patients with operated CHD and the usefulness of neuromarkers for the prediction of neurodevelopment outcomes. Methods: Prospective observational study in infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. We assessed the following variables: (1) serum biomarkers of brain injury (S100B, neuron-specific enolase) in cord blood and preoperative blood samples; (2) clinical and laboratory data from the immediate postnatal and perioperative periods; (3) treatments and complications; (4) neurodevelopment (Bayley-III scale) at age 2 years. Results: The study included 84 infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. Seventeen had univentricular heart, 20 left ventricular outflow obstruction and 10 genetic syndromes. The postoperative mortality was 5.9% (5/84) and 10.7% (9/84) patients experienced ANEs. The mean overall Bayley-III scores were within the normal range, but 31% of patients had abnormal scores in the cognitive, motor or language domains. Patients with genetic syndromes, ANEs and univentricular heart had poorer neurodevelopmental outcomes. Elevation of S100B in the immediate postoperative period was associated with poorer scores. Conclusions: Children with a history of cardiac surgery for CHD in the first year of life are at risk of adverse neurodevelopmental outcomes. Patients with genetic syndromes, ANEs or univentricular heart had poorer outcomes. Postoperative ANEs may contribute to poorer outcomes. Elevation of S100B levels in the postoperative period was associated with poorer neurodevelopmental outcomes at 2 years...(AU)

Clinical value of S100B in detecting intracranial injury in elderly patients with mild traumatic brain injury.

OBJECTIVE: The biomarker S100B is a sensitive biomarker to detect traumatic intracranial injury in patients mild traumatic brain injury (mTBI). Higher blood values of S100B, resulting in lower specificity and decreased head computed tomography (CT) reduction has been regarded as one of shortcomings in patients over 65 years of age. The purpose of this study was to assess the accuracy of plasma S100B to detect intracranial injury in elderly patients with mTBI. METHODS: A posthoc analysis was performed of a larger prospective cohort study. Previous recorded patient variables and plasma values of S100B from patients with mTBI who presented to the Emergency Department (ED) within 6 h of injury, underwent a head CT and had a blood sample drawn as part of their routine clinical care, were partitioned at 65 years of age. Sensitivity, specificity, negative predictive value, and positive predictive value of plasma S100B for predicting traumatic intracranial lesions on head CT, with a cut-off set at 0.105 µg/L, were calculated. Results were compared with data from an additional systematic review on the accuracy of S100B to detect intracranial injury in elderly patients with mTBI. RESULTS: Data of 240 patients (48.4 %) of 65 years or older were analyzed. Sensitivity and NPV of S100B were 89 % and 86 % respectively, which is lower than among younger patients (both 97 %). The specificity decreased stepwise with older age: 22 %, 18 %, and 5 % for the age groups 65-74, 75-84, and ≥ 85 years old, respectively. The meta-analysis comprised 4 studies and the current study with data from 2166 patients. Pooled data estimated the sensitivity of s100B as 97.4 % (95 % CI 83.3-100 %) and specificity as 17.3 % (95 % CI 9.5-29.3 %) to detect intracranial injury in elderly patients with mTBI. CONCLUSION: The biomarker S100B at the routine threshold has a limited clinical value in the management of elderly mTBI patients mainly due to a poor specificity leading to only a small decrease in head CTs. Alternate cut-off values and combining several plasma biomarkers with clinical variables may be useful strategies to increase the accuracy of S100B in (subgroups of) elderly mTBI patients.

Biological Markers in Newly Diagnosed Generalized Anxiety Disorder Patients: 8-OHdG, S100B and Oxidative Stress.

Purpose: Generalized Anxiety Disorder (GAD) is a chronic disease persisting for at least 6 months, characterized by excessive and continuous anxiety, which leads to evident problems and functional disorders. S100B is a glial protein that plays a role in intercellular communication regulating cell growth and differentiation, and intracellular signal transmission. This study aimed to analyze the serum S100B, 8-OHdG, and oxidative stress levels of patients newly diagnosed with GAD who had not started treatment, to better understand the underlying neurobiological basis of the etiology of GAD. Patients and Methods: Forty-four patients diagnosed with GAD according to DSM-5 diagnostic criteria and 44 healthy controls were included in the study. The Beck Anxiety Inventory (BAI) was used to determine the anxiety levels of the GAD patients. The serum S100B, 8-OHdG, total oxidant status (TOS), and total antioxidant status (TAS) levels were measured in the patient and control groups. Results: The 8-OHdG values of the GAD group were determined to be statistically significantly higher than those of the control group (p=0.028). No significant difference was determined between the GAD patients and the control group in respect of the TAS, TOS, and oxidative stress index (OSI) values (p>0.05). The S100B levels of the GAD group were found to be higher than those of the control group. Conclusion: The results of this study showed that there could be DNA damage because of oxidative stress in GAD patients. There is a need for further studies to confirm the role of S100B protein in GAD etiology and pathogenesis.

Minor head injury in anticoagulated patients: performance of biomarkers S100B, NSE, GFAP, UCH-L1 and Alinity TBI in the detection of intracranial injury. A prospective observational study.

OBJECTIVES: Data in literature indicate that in patients suffering a minor head injury (MHI), biomarkers serum levels could be effective to predict the absence of intracranial injury (ICI) on head CT scan. Use of these biomarkers in case of patients taking oral anticoagulants who experience MHI is very limited. We investigated biomarkers as predictors of ICI in anticoagulated patients managed in an ED. METHODS: We conducted a single-cohort, prospective, observational study in an ED. Our structured clinical pathway included a first head CT scan, 24 h observation and a second CT scan. The outcome was delayed ICI (dICI), defined as ICI on the second CT scan after a first negative CT scan. We assessed the sensitivity (SE), specificity (SP), negative predictive value (NNV) and positive predictive value (PPV) of the biomarkers S100B, NSE, GFAP, UCH-L1 and Alinity TBI in order to identify dICI. RESULTS: Our study population was of 234 patients with a negative first CT scan who underwent a second CT scan. The rate of dICI was 4.7 %. The NPV for the detection of dICI were respectively (IC 95 %): S100B 92.7 % (86.0-96.8 %,); ubiquitin C-terminal hydrolase-L1 (UCH-L1) 91.8 % (83.8-96.6 %); glial fibrillary protein (GFP) 100 % (83.2-100 %); TBI 100 % (66.4-100 %). The AUC for the detection of dICI was 0.407 for S100B, 0.563 for neuron-specific enolase (NSE), 0.510 for UCH-L1 and 0.720 for glial fibrillary acidic protein (GFAP), respectively. CONCLUSIONS: The NPV of the analyzed biomarkers were high and they potentially could limit the number of head CT scan for detecting dICI in anticoagulated patients suffering MHI. GFAP and Alinity TBI seem to be effective to rule out a dCI, but future trials are needed.

Predicting Short- and Long-Term Functional Outcomes Based on Serum S100B Protein Levels in Patients with Ischemic Stroke.

BACKGROUND: Ischemic stroke is one of the leading causes of mortality and disability. The neuroimaging methods are the gold standard for diagnostics. Biomarkers of cerebral ischemia are considered to be potentially helpful in the determination of the etiology and prognosis of patients with ischemic stroke. AIM: This study aimed to investigate the usefulness of serum S100B protein levels as a short- and long-term prognostic factor in patients with ischemic stroke. STUDY DESIGN AND METHODS: The study group comprised 65 patients with ischemic stroke. S100B protein levels were measured by immunoenzymatic assay. Short-term functional outcome was determined by the NIHSS score on day 1 and the difference in the NIHSS scores between day 1 and day 9 (delta NIHSS). Long-term outcome was assessed by the modified Rankin Scale (MRS) at 3 months after the stroke. At the end of the study, patients were divided into groups based on the NIHSS score on day 9 (0-8 "good" and >8 "poor"), the delta NIHSS ("no improvement" ≤0 and >0 "improvement"), and the MRS ("good" 0-2 and >2 "poor"). Differences in S100B levels between groups were analyzed with the ROC curve to establish the optimal cut-off point for S100B. The odds ratio was calculated to determine the strength of association. Correlations between S100B levels at three time points and these variables were evaluated. RESULTS: We revealed a statistically significant correlation between S100B levels at each measurement point (<24 h, 24-48 H, 48-72 h) and the NIHSS score on day 9 (R Spearman 0.534, 0.631, and 0.517, respectively) and the MRS score after 3 months (R Spearman 0.620, 0.657, and 0.617, respectively). No statistically significant correlation was found between S100B levels and the delta NIHSS. Analysis of the ROC curve confirmed a high sensitivity and specificity for S100B. The calculated AUC for the NIHSS on day 9 were 90.2%, 95.0%, and 82.2%, respectively, and for the MRS, 83.5%, 83.4%, and 84.0%, respectively. After determining the S100B cut-off, the odds ratio for beneficial effect (NIHSS ≤ 8 at day 9 or MRS 0-2 after 3 months) was determined for each sampling point. CONCLUSION: S100B is a useful marker for predicting short- and long-term functional outcomes in patients with ischemic stroke.

The Multifaceted S100B Protein: A Role in Obesity and Diabetes?

The S100B protein is abundant in the nervous system, mainly in astrocytes, and is also present in other districts. Among these, the adipose tissue is a site of concentration for the protein. In the light of consistent research showing some associations between S100B and adipose tissue in the context of obesity, metabolic disorders, and diabetes, this review tunes the possible role of S100B in the pathogenic processes of these disorders, which are known to involve the adipose tissue. The reported data suggest a role for adipose S100B in obesity/diabetes processes, thus putatively re-proposing the role played by astrocytic S100B in neuroinflammatory/neurodegenerative processes.

Elevated S100B urine levels predict seizures in infants complicated by perinatal asphyxia and undergoing therapeutic hypothermia.

OBJECTIVES: Seizures (SZ) are one of the main complications occurring in infants undergoing therapeutic hypothermia (TH) due to perinatal asphyxia (PA) and hypoxic ischemic encephalopathy (HIE). Phenobarbital (PB) is the first-line therapeutic strategy, although data on its potential side-effects need elucidation. We investigated whether: i) PB administration in PA-HIE TH-treated infants affects S100B urine levels, and ii) S100B could be a reliable early predictor of SZ. METHODS: We performed a prospective case-control study in 88 PA-HIE TH infants, complicated (n=44) or not (n=44) by SZ requiring PB treatment. S100B urine levels were measured at 11 predetermined monitoring time-points from first void up to 96-h from birth. Standard-of-care monitoring parameters were also recorded. RESULTS: S100B significantly increased in the first 24-h independently from HIE severity in the cases who later developed SZ and requested PB treatment. ROC curve analysis showed that S100B, as SZ predictor, at a cut-off of 2.78 µg/L achieved a sensitivity/specificity of 63 and 84 %, positive/negative predictive values of 83 and 64 %. CONCLUSIONS: The present results offer additional support to the usefulness of S100B as a trustable diagnostic tool in the clinical daily monitoring of therapeutic and pharmacological procedures in infants complicated by PA-HIE.

Neurodevelopmental outcomes in congenital heart disease: Usefulness of biomarkers of brain injury.

INTRODUCTION: At present, neurodevelopmental abnormalities are the most frequent type of complication in school-aged children with congenital heart disease (CHD). We analysed the incidence of acute neurologic events (ANEs) in patients with operated CHD and the usefulness of neuromarkers for the prediction of neurodevelopment outcomes. METHODS: Prospective observational study in infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. We assessed the following variables: (1) serum biomarkers of brain injury (S100B, neuron-specific enolase) in cord blood and preoperative blood samples; (2) clinical and laboratory data from the immediate postnatal and perioperative periods; (3) treatments and complications; (4) neurodevelopment (Bayley-III scale) at age 2 years. RESULTS: the study included 84 infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. Seventeen had univentricular heart, 20 left ventricular outflow obstruction and 10 genetic syndromes. The postoperative mortality was 5.9% (5/84) and 10.7% (9/84) patients experienced ANEs. The mean overall Bayley-III scores were within the normal range, but 31% of patients had abnormal scores in the cognitive, motor or language domains. Patients with genetic syndromes, ANEs and univentricular heart had poorer neurodevelopmental outcomes. Elevation of S100B in the immediate postoperative period was associated with poorer scores. CONCLUSIONS: children with a history of cardiac surgery for CHD in the first year of life are at risk of adverse neurodevelopmental outcomes. Patients with genetic syndromes, ANEs or univentricular heart had poorer outcomes. Postoperative ANEs may contribute to poorer outcomes. Elevation of S100B levels in the postoperative period was associated with poorer neurodevelopmental outcomes at 2 years. Studies with larger samples and longer follow-ups are needed to define the role of these biomarkers of brain injury in the prediction of neurodevelopmental outcomes in patients who undergo surgery for management of CHD.

Aggregation-induced signal amplification strategy based on peptide self-assembly for ultrasensitive electrochemical detection of melanoma biomarker.

The detection of melanoma circulating biomarker in liquid biopsies is current under evaluation for being potentially utilized for earlier cancer diagnosis and its metastasis. Herein, we developed a non-invasive electrochemical approach for ultrasensitive detection of the S100B, serving as a potential promising blood circulating biomarker of melanoma, based on an aggregation-induced signal amplification (AISA) strategy via in-situ peptide self-assembly. The fundamental principle of this assay is that the designed amphiphilic peptides (C16-Pep-Fc), fulfilling multiple functions, feature both a recognition region for specific binding to S100B and an aggregation (self-assembly) region for the formation of peptide nanomicelles under mild conditions. The C16 tails were encapsulated within the hydrophobic core of the aggregates, while the relatively hydrophilic recognition fragment Pep and Fc tag were exposed on the outer surface for subsequent recognition of S100B and signal output. AISA provided remarkable accumulation of electroactive Fc moieties that enabled ultrasensitive S100B detection of as low as 0.02 nM, which was 10-fold lower than un-amplified approach and better than previously reported assays. As a proof-of-concept study, further experiments also highlighted the good reproducibility and stability of AISA and demonstrated its usability when applied to simulated serum samples. Hence, this work not only presented a valuable assay tool for ultrasensitive detecting protein biomarker, but also advocated for the utilization of aggregation-induced signal amplification in electrochemical biosensing system, given its considerable potential for future practical applications.

Recent Advance of S100B Proteins in Spontaneous Intracerebral Hemorrhage and Aneurysmal Subarachnoid Hemorrhage.

Human health is seriously endangered by spontaneous intracerebral hemorrhage (ICH) and aneurysmal subarachnoid hemorrhage (aSAH). Because the majority of ICH and aSAH survivors experience disability, increased risk of stroke recurrence, cognitive decline, and systemic vascular disease, ICH and aSAH assume special importance in neurological disease. Early detection and prediction of neurological function and understanding of etiology and correction are the basis of successful treatment. ICH and aSAH cause complex inflammatory cascades in the brain. In order to establish precise staging and prognosis, as well as provide a basis for treatment selection and monitoring, it is imperative to determine appropriate biological markers according to pathological and physiological mechanisms. In this review, we focus on the research progress of S100B, an endogenous danger signaling molecule, as a potential biomarker for ICH and aSAH, assisting in the development of further basic research and clinical translational studies.