Neuron-specific Enolase Concentrations Research Articles

Label-Free Assessment of Neuron-Specific Enolase via Polydopamine over a Carbon-Nanotube-Based Flexible Immunosensor.

A label-free electrochemical immunosensor was developed for the rapid and sensitive detection of neuron-specific enolase (NSE). The electropolymerization of dopamine in conjunction with highly conductive carbon nanotubes offers a simple and quick platform for the direct anchoring of antibodies without the assistance of any coupling agent as well as a blocking agent. The developed immunosensor exhibited a wider detection range from 120 pM (9 ng mL-1) to 3 nM (200 ng mL-1) for NSE with a high sensitivity of 3.9 μA pM-1 cm-2 in 0.1 M phosphate-buffered saline (PBS) at physiological pH (7.4). Moreover, the short recognition time (15 min) for the antigen enabled the detection to be fast and less invasive. Additionally, the evaluation of a rate constant at various concentrations of NSE via feedback mode of scanning electrochemical microscopy (SECM) explained the profound effect of antigen concentration on the rate of flow of electrons. Therefore, the proposed immunosensor can be a promising tool for the early detection of small cell lung cancer in a very short period of time with consistent accuracy.

Predictive value of TCCD and regional cerebral oxygen saturation for detecting early postoperative brain injury.

This study aims to analyze the risk factors for early postoperative brain injury in patients undergoing cardiovascular surgery and explore the predictive value of transcranial color Doppler (TCCD) and regional cerebral oxygen saturation (rSO2) for detecting early postoperative brain injury in cardiovascular surgery patients. A total of 55 patients undergoing cardiovascular surgery with cardiopulmonary bypass in Changzhou No.2 The People's Hospital of Nanjing Medical University were included in this study. Neuron-specific enolase (NSE) concentration was measured 24h after operation. Patients were divided into brain injury (NSE ≥ 16.3 ng/mL) and normal (0 < NSE < 16.3 ng/mL) groups according to the measured NSE concentration. The clinical outcomes between the two groups were compared, including decreased rSO2 and cerebral blood flow (as measured by TCCD) levels. The risk factors of early postoperative brain injury were analyzed by multivariate logistic regression analysis, and the significant variables were analyzed by receiver operating characteristic (ROC) analysis. A total of 50 patients were included in this study, with 20 patients in the brain injury group and 30 patients in the normal group. Cardiopulmonary bypass time (min) (107 ± 29 vs. 90 ± 28, P = 0.047) and aortic occlusion time (min) (111 (IQR 81-127) vs. 87 (IQR 72-116), P = 0.010) were significantly longer in the brain injury group than in the normal group. Patients in the brain injury group had greater decreased rSO2 (%) (27.0 ± 7.3 vs. 17.5 ± 6.1, P < 0.001) and cerebral blood flow (%) (44.9 (IQR 37.8-69.2) vs. 29.1 (IQR 12.0-48.2), P = 0.004) levels. Multivariate logistic regression analysis suggested that decreased rSO2 and cerebral blood flow levels, aortic occlusion time, and history of atrial fibrillation were independent risk factors for early postoperative brain injury (P < 0.05). ROC analysis reported that the best cutoff values for predicting early postoperative brain injury were 21.4% and 37.4% for decreased rSO2 and cerebral blood flow levels, respectively (P < 0.05). The decreased rSO2 and cerebral blood flow levels, aorta occlusion time, and history of atrial fibrillation were independent risk factors for early postoperative brain injury. TCCD and rSO2 could effectively monitor brain metabolism and cerebral blood flow and predict early postoperative brain injury.

A nomogram based on neuron-specific enolase and substantia nigra hyperechogenicity for identifying cognitive impairment in Parkinson's disease.

One in four individuals with Parkinson's disease (PD) experience cognitive impairment (CI). However, few practical models integrating clinical and neuroimaging biomarkers have been developed to address CI in PD. This study aimed to evaluate the correlation between circulating neuron-specific enolase (NSE) levels, substantia nigra hyperechogenicity (SNH), and cognitive function in PD and to develop a nomogram based on clinical and neuroimaging biomarkers for predicting CI in patients with PD. A total of 385 patients with PD who underwent transcranial sonography (TCS) from January 2021 to December 2022 at Beijing Tiantan Hospital, Capital Medical University, were recruited as the training cohort. For validation, 165 patients with PD treated from January 2023 to December 2023 were enrolled. Data for SNH, plasma NSE, and other clinical measures were collected, and cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Logistic regression analysis was employed to select potential risk factors and establish a nomogram. The receiver operating characteristic curve and calibration curve were generated to evaluate the performance of the nomogram. Patients with PD exhibiting CI displayed advanced age, elevated Unified PD Rating Scale-III (UPDRS-III) score, an increased percentage of SNH, higher levels of plasma NSE and homocysteine (Hcy), a larger SNH area, and lower education levels compared to PD patients without CI. Gender [odds ratio (OR) =0.561, 95% confidence interval (CI): 0.330-0.954, P=0.03], age (OR =1.039; 95% CI: 1.011-1.066; P=0.005), education level (OR =0.892; 95% CI: 0.842-0.954; P<0.001), UPDRS-III scores (OR =1.026; 95% CI: 1.009-1.043; P=0.003), plasma NSE concentration (OR =1.562; 95% CI: 1.374-1.776; P<0.001), and SNH (OR =0.545; 95% CI: 0.330-0.902; P=0.02) were independent predictors of CI in patients with PD. A nomogram developed using these six factors yielded a moderate discrimination performance with an area under the curve (AUC) of 0.823 (95% CI 0.781-0.864; P<0.001). The calibration curve demonstrated acceptable agreement between predicted outcomes and actual values. Validation further confirmed the reliability of the nomogram, with an AUC of 0.864 (95% CI: 0.805-0.922; P<0.001). The level of NSE in plasma and the SNH assessed by TCS are associated with CI in patients with PD. The proposed nomogram has the potential to facilitate the detection of cognitive decline in individuals with PD.

Serum Neuron-Specific Enolase as a Biomarker of Neonatal Brain Injury-New Perspectives for the Identification of Preterm Neonates at High Risk for Severe Intraventricular Hemorrhage.

Neonatal brain injury (NBI) is a critical condition for preterm neonates with potential long-term adverse neurodevelopmental outcomes. This prospective longitudinal case-control study aimed at investigating the levels and prognostic value of serum neuron-specific enolase (NSE) during the first 3 days of life in preterm neonates (<34 weeks) that later developed brain injury in the form of either periventricular leukomalacia (PVL) or intraventricular hemorrhage (IVH) during their hospitalization. Participants were recruited from one neonatal intensive care unit, and on the basis of birth weight and gestational age, we matched each case (n = 29) with a neonate who had a normal head ultrasound scan (n = 29). We report that serum NSE levels during the first three days of life do not differ significantly between control and preterm neonates with NBI. Nevertheless, subgroup analysis revealed that neonates with IVH had significantly higher concentrations of serum NSE in comparison to controls and neonates with PVL on the third day of life (p = 0.014 and p = 0.033, respectively). The same pattern on the levels of NSE on the third day of life was also observed between (a) neonates with IVH and all other neonates (PVL and control; p = 0.003), (b) neonates with II-IV degree IVH and all other neonates (p = 0.003), and (c) between control and the five (n = 5) neonates that died from the case group (p = 0.023). We conclude that NSE could be an effective and useful biomarker on the third day of life for the identification of preterm neonates at high risk of developing severe forms of IVH.

Identification of risk factors of EGFR-TKIs primary resistance in lung adenocarcinoma patients and construction of a risk predictive model: a case-control study.

Lung cancer is one of the malignancies with the highest incidence and mortality rates. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are recommended as the first-line treatment for patients with EGFR-mutated lung adenocarcinoma (LUAD). However, some patients with EGFR-sensitive mutations develop primary resistance to EGFR-TKIs. This study aims to analyze the clinical characteristics of LUAD patients with primary resistance to EGFR-TKIs, identify independent risk factors for primary resistance, and establish a risk predictive model to provide reference for clinical decision-making. We collected data from LUAD patients with EGFR-sensitive mutations (19del/21L858R) who were hospitalized in our institution between 2020 and 2022 and received first-generation EGFR-TKIs with follow-up exceeding 6 months. These patients were categorized into primary resistance and sensitive groups based on treatment outcomes. We compared general clinical data, laboratory tests, and tumor-related characteristics between the two groups, analyzed risk factors for primary resistance to EGFR-TKIs, and constructed a risk predictive model. The model's predictive value was comprehensively assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curves. Serum neuron-specific enolase (NSE) concentration (P=0.03), serum pro-gastrin-releasing peptide (ProGRP) concentration (P=0.01), and Ki67 expression (P<0.001) were identified as independent risk factors for primary resistance to EGFR-TKIs in LUAD. The combined presence of these three risk factors had the highest predictive value [area under the curve (AUC) =0.975, P<0.001]. We constructed a predictive model for the risk of primary resistance to EGFR-TKIs in LUAD patients, incorporating these three parameters, and represented it through a visually interpretable nomogram. The calibration curve of the nomogram demonstrated its strong predictive ability. Further decision curve analysis indicated the model's clinical utility. Based on a single-center retrospective case-control study, we identified serum NSE concentration, ProGRP concentration, and Ki67 expression as independent risk factors for primary resistance to EGFR-TKIs in LUAD patients. We constructed and validated a risk predictive model based on these findings. This predictive model holds promise for clinical application, aiding in the development of personalized treatment strategies and providing a scientific basis for early identification of primary resistance patients.

Moxibustion preconditioning reduces inflammatory response in rats with cerebral ischemia-reperfusion injury by regulating PI3K / AKT / mTOR signaling pathway.

To observe the effect of moxibustion preconditioning on inflammatory response in rats with cerebral ischemia reperfusion injury (CIRI), so as to explore its mechanisms underlying improving CIRI. Seventy-five male SD rats were randomly divided into sham operation, model, moxibustion preconditioning 3 days (Moxi 1), moxibustion preconditioning 5 days (Moxi 2) and moxibustion preconditioning 7 days (Moxi 3) groups, with 15 rats in each group. Moxibustion was applied at "Baihui"(GV20), "Dazhui"(GV14) and "Zusanli"(ST36) for 20 min once a day, totally for 3, 5 or 7 days. Thirty minutes after the last moxibustion treatment, the CIRI model was established by occlusion of the middle cerebral artery. The neurological deficit score was assessed by using Longa's method. The infarct size of the brain assessed after staining with 2% triphenyltetrazolium chloride (TTC). The morphological changes of cortical neurons were observed by HE staining. The contents of inflammatory factors interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), S-100β protein (S-100β) and neuron-specific enolase (NSE) were detected by ELISA. The expression of phosphatidylinositol-3-kinase (PI3K), p-PI3K, protein kinase B (AKT) and mammalian target of rapamycin (mTOR) proteins in the ischemic cortex tissues were detected by immunohistochemistry and Western blot. Compared with the sham operation group, the neurological function score and the percentage of cerebral ischemic volume were increased (P<0.01). The contents of serum IL-1β, TNF-α, S-100β and NSE were significantly increased (P<0.01), while the protein expressions of PI3K, p-PI3K, AKT and mTOR in the cerebral cortex were significantly decreased (P<0.01) in the model group. Compared with the model group, the neurological function score and the percentage of cerebral ischemic volume were significantly decreased (P<0.01). The contents of serum IL-1β, TNF-α, S-100β and NSE were significantly decreased (P<0.01), and the expressions of PI3K, p-PI3K, AKT and mTOR proteins in the cerebral cortex were significantly increased (P<0.01) in three moxibustion groups. Compared with the Moxi 1 and Moxi 2 groups, the above indicators were significantly improved in rats of the Moxi 3 group (P<0.01, P<0.05). Moxibustion preconditioning can significantly improve the neurological function of rats after ischemia-reperfusion, inhibit serum inflammatory factors IL-1 β and TNF-α, inhibit brain tissue injury markers S-100β and NSE, which may be related to the activation of PI3K/AKT/mTOR signaling pathway. The protective effect of moxibustion preconditioning for 7 days on CIRI was better than that of 5 days and 3 days.

Novel immunosensor based on electrochemiluminescence inner filter effect and static quenching between fibrillary Ag-MOGs and SiO2@PANI@AuNPs for enabling the sensitive detection of neuron-specific enolase.

Metal-organic gels (MOGs) are unique supramolecular gels that are convenient to synthesize. In this work, a cathodic electrochemiluminescence (ECL) system based on Ag-MOGs as a luminophore and K2S2O8 as a co-reactor was developed. The ECL spectrum of the Ag-MOGs overlapped significantly with the strong UV-Vis spectrum of the SiO2@PANI@AuNPs, which effectively quenched the ECL luminescence of the Ag-MOGs. Relying on theinner filter effect between Ag-MOGs and SiO2@PANI@AuNPs, a novel ECL-IFE immunosensor was developed for the detection of neuron-specific enolase (NSE). Under optimal conditions, the ECL signal of the immunosensor displayed excellent linearity over the NSE concentration range of 10 fg/mL-100 ng/mL. The limit of detection (LOD) was 2.6 fg/mL (S/N = 3) with a correlation coefficient R2 of 0.9975. The ECL immunosensor also exhibited excellent stability and reproducibility for the detection of NSE. The results reported provide afeasible concept for the development analytical methods for the detection of other clinically relevant biomarkers.

Meta-analysis of evaluating neuron specific enolase as a serum biomarker for sepsis-associated encephalopathy

IntroductionBrain dysfunction in sepsis is known as Sepsis-associated encephalopathy (SAE), which often results in severe cognitive and neurological sequelae and increases the risk of death. Neuron specific enolase (NSE) may serve as an important neurocritical biomarker for detection and longitudinal monitoring in SAE patients. Our Meta-analysis aimed to explore the diagnostic and prognostic value of serum NSE in SAE patients. Currently, no systematic Review and Meta-analysis have been assessed that NSE as a biomarker of SAE. MethodsThe study protocol was registered in the PROSPERO database (CRD42023398736) and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We conducted a systematic review and Meta-analysis to evaluate the serum NSE’s diagnostic accuracy for SAE and prognostic strength for probability of death of septic patients. We systematic searched electronic bibliographic databases from PubMed, MEDLINE, Web of Science, Embase, Cochrane databases, CNKI, CQVIP, and WFSD. QUADAS-2 assessment tool was used to evaluate quality and risk of bias of the selected studies. Subgroup analyses, funnel plots, sensitivity analyses were also carried out. Review Manager version 5.4 and Stata16.0. was used for statistical analysis. ResultsThis Meta-analysis included 22 studies with 1361 serum samples from SAE patients and 1580 serum samples from no-encephalopathy septic (NE) patients. The Meta-analysis showed that individuals with SAE had higher serum NSE level than NE controls (SMD 1.93 (95 % CI 1.51–2.35), P < 0.00001). In addition, there are 948 serum samples from survival septic patients and 446 serum samples from non-survival septic patients, septic patients with survival outcomes had lower serum NSE levels than those with death outcomes (SMD −1.87 (95 % CI −2.43 to −1.32), P < 0.00001). ConclusionOur Meta-analysis reveals a significant association between elevated NSE concentrations and the increased likelihood of concomitant SAE and mortality during septic patients. This comprehensive analysis will equip ICU physicians with up-to-date insights to accurately identify patients at risk of SAE and implement appropriate intervention strategies to mitigate morbidity and improve neurological outcomes. However, it is important to note that the presence of substantial heterogeneity among studies poses challenges in determining the most effective discrimination cutoff values and optimal sampling collection time.

Toxoplasma gondii infection associated with inflammasome activation and neuronal injury

Toxoplasma gondii (TOXO) infection typically results in chronic latency due to its ability to form cysts in the brain and other organs. Latent toxoplasmosis could promote innate immune responses and impact brain function. A large body of evidence has linked TOXO infection to severe mental illness (SMI). We hypothesized that TOXO immunoglobulin G (IgG) seropositivity, reflecting previous infection and current latency, is associated with increased circulating neuron-specific enolase (NSE), a marker of brain damage, and interleukin-18 (IL-18), an innate immune marker, mainly in SMI. We included 735 patients with SMI (schizophrenia or bipolar spectrum) (mean age 32 years, 47% women), and 518 healthy controls (HC) (mean age 33 years, 43% women). TOXO IgG, expressed as seropositivity/seronegativity, NSE and IL-18 were measured with immunoassays. We searched for main and interaction effects of TOXO, patient/control status and sex on NSE and IL-18. In the whole sample as well as among patients and HC separately, IL-18 and NSE concentrations were positively correlated (p < 0.001). TOXO seropositive participants had significantly higher NSE (3713 vs. 2200 pg/ml, p < 0.001) and IL-18 levels (1068 vs. 674 pg/ml, p < 0.001) than seronegative participants, and evaluation within patients and HC separately showed similar results. Post-hoc analysis on cytomegalovirus and herpes simplex virus 1 IgG status showed no associations with NSE or IL-18 which may suggest TOXO specificity. These results may indicate ongoing inflammasome activation and neuronal injury in people with TOXO infections unrelated to diagnosis.

Electroacupuncture Therapy Effectively Protects the Rat Brain after Intracerebral Hemorrhage

Objective. Electroacupuncture (Ea) is a useful complementary and alternative therapy for intracerebral hemorrhage (ICH). However, the neurobiological basis for the Ea treatment of ICH is still unclear. The primary aim of the present study was to explore whether Ea prevents brain edema, apoptosis, excitotoxicity, and neuroinflammation in rats after hemorrhagic stroke. Methods. Rats were randomly divided into Sham, Control, and Ea groups. We used modified neurological severity score (mNSS) and gait analysis to estimate neurological function in rats, and PET/CT to assess glucose uptake and the hemorrhagic focus volume. Measurement of the brain water content and TUNEL staining were used to evaluate brain edema and cell apoptosis, respectively. The serum myelin basic protein (MBP), neuron-specific enolase (NSE), calcium-binding protein B (S100B), and tumor necrosis factor-α (TNF-α) concentrations were examined with ELISA. The expression levels of the CD68, GALC, Arg-1, iNOS, NR2A, Glu2R, AQP4, MAP2, GFAP, AQP9, Bcl-2, Bax, and Glu proteins around the hematoma were detected via immunohistochemistry staining. Western blot was used to analyze the levels of the AQP4, AQP9, Bax, Bcl-2, iNOS, and Arg-1 proteins. Results. Ea treatment improved neurological function and reduced the hemorrhagic area and brain water content in rats after ICH. The serum concentrations of MBP, NSE, S100B, and TNF-α all decreased significantly in the Ea group compared with the Control group. Expression levels of the Glu, NR2A, AQP4, AQP9, Bax, GFAP, iNOS, and CD68 proteins in brain tissue surrounding the hematoma were obviously suppressed in ICH rats following Ea treatment. Moreover, Ea stimulation increased the levels of the MAP2, GALC, Glu2R, Arg-1, and Bcl-2 proteins, but reduced the number of TUNEL-positive cells in rats after ICH. Conclusion. The results of this study suggest that Ea may exert neuroprotective effects by suppressing brain edema, apoptosis, excitotoxicity, and neuroinflammation.

Clinical value of serum DJ-1 in lung adenocarcinoma.

DJ-1 is an oncoprotein secreted by cancer cells. However, the physiological and pathological significance of DJ-1 secretion is not clearly understood. This study investigated the clinical value of serum DJ-1 in lung adenocarcinoma (LUAD). The study involved 224 LUAD patients, 110 patients with benign pulmonary disease and 100 healthy controls from the First Affiliated Hospital of Nanjing Medical University. We detected the expression of DJ-1 in lung cell lines in vitro. Meanwhile, serum concentrations of DJ-1, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and cytokeratin 19 fragment (CYFRA21-1) were measured. The diagnostic performance of LUAD was obtained using receiver operating characteristic (ROC) curves. Kaplan-Meier, univariate and multivariate Cox regression analyses were performed for progression-free survival (PFS). DJ-1 was highly expressed in LUAD cell lines. Serum DJ-1 levels were significantly higher in the LUAD group compared to the benign pulmonary disease group (5.04 vs. 3.66 ng/mL, P<0.001) and healthy controls (5.04 vs. 3.51 ng/mL, P<0.001). DJ-1 levels were associated with gender (P=0.002), smoking history (P=0.042) and lymph node metastasis (P=0.040). ROC curve analysis of DJ-1 revealed an area under the curve (AUC) of 0.758 (95% CI [0.714-0.803], P<0.001) with a sensitivity of 63.8% and specificity of 78.6% at a cutoff value of 4.62 ng/mL for the detection of LUAD. Univariate and multivariate analyses confirmed that the preoperative serum DJ-1 level, tumor stage and smoking history were independent prognostic factors of PFS. Our study is the first to explore the clinical value of serum DJ-1 in LUAD comprehensively. Serum DJ-1 could be a potential diagnostic and prognostic biomarker for LUAD.

Effects of parecoxib on postoperative cognitive dysfunction and serum levels of NSE and S100β in elderly patients undergoing surgery.

To investigate the effects of parecoxib on postoperative cognitive dysfunction, and serum levels of neuron-specific enolase (NSE) and S100β protein (S100β) in elderly patients undergoing surgery. The retrospective cohort study method was used to collect the clinical data of 94 elderly patients who underwent elective orthopedic and general anesthesia surgery in our hospital from September 2020 to February 2022. 94 patients were divided into the control group (47 cases) and the study group (47 cases), according to different intervention methods. In the study group, 40 mg of parecoxib was injected intravenously into patients 30 min before the induction of anesthesia, and the patients in the control group were given the same dose of normal saline intravenously before the operation. The basic clinical data of the patients were collected. The levels of the indexes before operation and 6 hours after operation were compared between the two groups, including the Montreal Cognitive Scale (MoCA) score, inflammatory factor indicators [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), interleukin-10 (IL-10), interleukin-1β (IL-1β), monocyte chemokine-1 (MCP-1), and inducible nitric oxide synthase (iNOS)], serum cortisol (CORT), beta-amyloid (β-AP), adiponectin (ADP), NSE, and S100β. No significant differences in the preoperative MoCA score, TNF-α, IL-6, CRP, IL-10, IL-1β, MCP-1, iNOS, CORT, β-AP, ADP, NSE, and S100β levels were observed between the two groups (p>0.05). The postoperative MoCA score in the study group was significantly higher than that in the control group (p<0.05). The postoperative levels of TNF-α, IL-6, CRP and IL-1β in the study group were significantly lower than those in the control group (p<0.05), and the postoperative levels of IL-10, MCP-1 and iNOS in the study group were significantly higher than those in the control group (p<0.05). Parecoxib can notably inhibit the levels of postoperative inflammatory cytokines, improve neurological dysfunction, and reduce the occurrence of postoperative cognitive dysfunction in patients. The contents of serum NSE and S100β have potential value in the diagnosis of postoperative cognitive dysfunction in elderly patients.

Plasma neuron specific enolase (NSE), tumour necrosis factor-alpha (TNF-α) and soluble IL-2 receptor alpha (sIL-2Rα) levels in children with developmental delay (DD): Use of combined ROC curves to increase their diagnostic value

BackgroundDevelopmental delay (DD) occurs when children fail to reach developmental milestones in comparison to peers of the same age range. However, there are no valuable biomarkers for the early diagnosis of DD. Since there is no specific marker for screening the disease, we evaluated plasma NSE, TNF-α and sIL2-Rα as potential markers for this purpose. MethodsIn this cross-sectional randomized case-control study, a total of 174 DD patients and 49 matched elderly controls aged between 2 months and 60 months were recruited. A sensitive enzyme-linked immunosorbent assay and an immunoradiometric assay were used to evaluate the levels of plasma IL-1, IL-6, IL-8, IL-10, sIL2-Rα, TNF-α, and NSE. Statistical analyses using t test, χ2, ANOVA, ROC curves and binary logistic regression models were performed. ResultsIn comparison to the control group, the DD group had greater levels of NSE, TNF-α, and sIL2-Rα(p < 0.05). In the binary logistic regression analysis of DD, NSE had an odds ratio (OR) of 1.783 (95 % CI 1.297 to 2.451, p = 0.000), indicating that NSE was an independent risk factor for DD. The plasma TNF-α level was positively correlated with plasma NSE and sIL2-Rα levels in the DD group (r = 0.366 and 0.433, respectively), and the DQ score and plasma sIL2-Rα level in the DD group were positively correlated. The ROC curve revealed that the respective areas under the NSE, TNF-α, and sIL2-Rα ROC curves were 0.9797, 0.9365, and 0.8533, respectively. Moreover, a significant increase in AUC was observed using combined ROC curve analysis. ConclusionsChildren with DD have significantly altered plasma concentrations of sIL2-Rα, NSE, and TNF-α. NSE, TNF-α and sIL2-Rα can be used as DD blood biomarkers. This information may be helpful in early diagnosis and intervention.

Surveilling brain damage using brain biomarkers in hypoglycemic neonatal calves with diarrhea.

Hypoglycemia is a condition associated with neonatal diarrhea in calves, leading to increased mortality and neurological clinical signs. The aim of the present study was to determine the development of brain damage in hypoglycemic calves with neonatal diarrhea and the diagnostic and prognostic significance of these biomarkers. Ten healthy and 50 hypoglycemic calves with diarrhea were included in the study. Clinical examination, blood gases and complete blood count were performed at admission. Blood serum calcium-binding protein B (S100B), neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal hydrolysis isoenzyme-1 (UCHL-1), activitin A (ACT), adrenomodullin (AM) concentrations, and creatine kinase-BB (CK-BB) enzyme activity were measured using commercial bovine-specific ELISA kits to assess brain damage. Of the hypoglycemic calves enrolled in the study, 13 (26%) survived and 37 (74%) died. In addition, 32 (64%) of the calves had severe acidosis and 24 (48%) had sepsis. S100B, GFAP, UCHL-1, CK-BB (p < 0.001) and NSE (p < 0.05) concentrations were significantly higher in hypoglycemic calves compared to healthy calves, while ACT concentrations were lower. Blood glucose concentration was negatively correlated with serum S100B, GFAP, UCHL-1, and CK-BB enzyme activity and positively correlated with ACT in hypoglycemic calves (p < 0.01). Brain injury biomarkers were not predictive of mortality (p > 0.05). Morever, severe hypoglycemia, severe acidosis and sepsis variables were not found to have sufficient capacity to predict mortality when considered alone or together (p > 0.05). In conclusion, brain damage may develop as a consequence of hypoglycemia in calves. S100B, NSE, GFAP, UCHL-1, ACT, and CK-BB concentrations can be used to diagnose brain damage in hypoglycemic calves. However, the variables of severe hypoglycemia, severe acidosis, and sepsis together with the biomarkers of brain injury have a limited value in predicting the prognosis of neonatal calves with diarrhea.

Exploring the application value of pro-gastrin-releasing peptide in the clinical diagnosis and surgical treatment of medullary thyroid carcinoma.

To investigate the relationship between pro-gastrin-releasing peptide (ProGRP) and the clinical characteristics of patients with medullary thyroid carcinoma (MTC) and the value of ProGRP in surgical treatment monitoring. A total of 347 patients with MTC and non-MTC malignant and benign thyroid diseases were enrolled. The concentrations of neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), calcitonin (CT), and ProGRP were determined by Elecsys® assays. The NSE, CEA, CT, and ProGRP levels in different thyroid disease groups were compared, and ProGRP levels in different clinicopathological feature groups pre and postoperatively were further compared. The CT, CEA, NSE, and ProGRP levels were upregulated in the MTC group compared to those in the non-MTC malignant and benign thyroid disease groups. The area under the receiver operating characteristic curve (AUC) of ProGRP for the diagnosis of MTC was 0.832(0.787-0.871), similar to that of CT and CEA. The sensitivity and specificity were 71.4% and 92.7%, respectively, and the optimal cut-off value was 61.8 pg/mL. The AUC of ProGRP combined with CT or CEA for the diagnosis of MTC was 0.933 (0.900-0.958) and 0.922 (0.886-0.949), respectively, which were higher than those of a single index. ProGRP levels were higher in patients with lymph nodes and distant metastases than in patients without metastases. The postoperative level of ProGRP was lower than that before treatment. ProGRP is comparable to CEA and CT as an MTC biomarker with broad prospects. It has potential application value in the progression of MTC assessment and the evaluation of surgical intervention effects.

Effects of remote ischemic preconditioning in severe traumatic brain injury: A single-center randomized controlled trial.

Traumatic brain injury (TBI) is a significant contributor to global mortality and impairment. Experimental data has shown the advantages of remote ischemic preconditioning (RIPC) in treating brain injury, however, there is a lack of evidence-based medicine regarding its clinical effectiveness and safety. In this study, we investigated whether RIPC could enhance outcomes in patients with severe TBI. Between January 2019 and December 2022, a comprehensive assessment was conducted on 392 individuals with severe TBI. Out of these, 304 patients were initially included and randomly assigned to receive either RIPC treatment (n = 153) or a control treatment (n = 151). The main measures of results included Glasgow Outcome Scale scores at 6 months, the occurrence of cerebral infarction during hospitalization, mortality rate within 30 days, levels of neuron-specific enolase and S-100β, any adverse effects, expenses incurred during hospitalization, and duration of hospital stay. The 2 groups did not show any statistically significant differences in baseline clinical data. The Glasgow Outcome Scale scores at 6 months in the RIPC group showed significant improvement when compared with the control group. Additionally, the application of RIPC therapy can reduce the concentrations of neuron-specific enolase and S-100β. There was no notable distinction observed between the 2 groups regarding the adverse reactions of RIPC-induced objective indications of tissue or neurovascular harm. In the RIPC group, there was a significant reduction in both the duration of hospital stays and the expenses associated with hospitalization. The results of this study suggest that RIPC has the potential to enhance clinical outcomes, mitigate nerve damage, and reduce both hospital expenses and length of stay in patients with severe TBI. The use of RIPC is a reliable and efficient method for managing severe TBI.

Impaired glucose utilization in the brain of patients with delirium following hip fracture.

Alterations in brain energy metabolism have long been proposed as one of several neurobiological processes contributing to delirium. This is supported by previous findings of altered CSF lactate and neuron-specific enolase concentrations and decreased glucose uptake on brain-PET in patients with delirium. Despite this, there are limited data on metabolic alterations found in CSF samples, and targeted metabolic profiling of CSF metabolites involved in energy metabolism has not been performed. The aim of the study was to investigate whether metabolites related to energy metabolism in the serum and CSF of patients with hip fracture are associated with delirium. The study cohort included 406 patients with a mean age of 81 years (standard deviation 10 years), acutely admitted to hospital for surgical repair of a hip fracture. Delirium was assessed daily until the fifth postoperative day. CSF was collected from all 406 participants at the onset of spinal anaesthesia, and serum samples were drawn concurrently from 213 participants. Glucose and lactate in CSF were measured using amperometry, whereas plasma glucose was measured in the clinical laboratory using enzymatic photometry. Serum and CSF concentrations of the branched-chain amino acids, 3-hydroxyisobutyric acid, acetoacetate and β-hydroxybutyrate were measured using gas chromatography-tandem mass spectrometry (GC-MS/MS). In total, 224 (55%) patients developed delirium pre- or postoperatively. Ketone body concentrations (acetoacetate, β-hydroxybutyrate) and branched-chain amino acids were significantly elevated in the CSF but not in serum among patients with delirium, despite no group differences in glucose concentrations. The level of 3-hydroxyisobutyric acid was significantly elevated in both CSF and serum. An elevation of CSF lactate during delirium was explained by age and comorbidity. Our data suggest that altered glucose utilization and a shift to ketone body metabolism occurs in the brain during delirium.

A Swine Model of Neural Circuit Electromagnetic Fields: Effects of Immediate Electromagnetic Field Stimulation on Cortical Injury.

Background Neurologic diseases have profound disability, mortality, and socioeconomic effects worldwide. Treatment of these disorders varies but is largely limited to unique factors associated with neural physiology. Early studies have evaluated alterations in electromagnetic fields (EMF) due to neural disorders with subsequent modulation of EMF as a potential treatment modality. Swine models have begun to be evaluated as translational models in this effect. Methods EMF measurements of a Yucatan miniswine were recorded using proprietary non-contact, non-invasive induction sensors with a dual layer Mu-metal and interlaced copper mesh helmet. The swine then underwent controlled cortical impact (CCI) to simulate traumatic brain injury (TBI). Twenty minutes post-injuryafter surgical wound closure, the swine underwent targeted EMF signal modulation using a signal generator to stimulate the swine's injured cortical circuit using a sinusoidal wave individualized at 2.5 Hz with a 500mV positive offset at 1V. After 10 days of stimulation, settings were modified to another individualized frequency of 5.5 Hz, 500mV positive offset and 1V for stimulation. Behavioral patterns in swine were evaluated, and EMF measurements were recorded daily prior to, during, and after stimulation. Artificial intelligence (AI) models evaluated patterns in EMF signals.Histology of the stimulated swine cortex was evaluated using hematoxylin and eosin staining and pentachrome staining and compared to a control swine without stimulation and a swine that had received stimulation two days post-injury in a delayed fashion. Serial serum specimens and tissue at the time of euthanasia were obtained for assessment of neuron-specific enolase (NSE) concentration. Results Pre-operative and post-stimulation measurements demonstrated differences in patterns and activity early on. There was an identified peak at 1.6Hz, not frequently seen pre-operatively. There were convergent frequencies in both data setsat 10.5 Hz and 3.9 Hz. Plateaus and decreased variability of changes in slope were identified early in the post-injury phase. AI modeling identified early similarities in pre-operative and post-stimulation measurements through the patterns of peaks with similarities on postoperative day 10 and similarities in the valleys on postoperative day 17.Histologic specimens identified increased degrees of apoptosis and cellular death in the non-stimulated control compared to the stimulated swine. Similarly, the immediately stimulated swine had less apoptosis and increased histologic viability at the site of injury compared to the two-day delayed stimulation swine. There were increased levels of NSE noted in the stimulated swine at the site of injury compared to non-injured sites and the control swine. Conclusions Cortical function was appropriately measured through induction sensors and shielding in the form of a helmet and electromagnetic field channels. Early stimulation resulted in the early and durable recovery of neuronal circuit-driven electromagnetic field patterns. Histology identified increased viability of neurons with fewer apoptotic neurons and glial cells in stimulated swine with early stimulation identifying the best effect compared to a non-stimulated subject. This recovery identifies change and recovery at the circuit, cellular, and subcellular levels that potentiatethe need for further study of EMF modulation as a treatment modality in neurological disorders.

Predicting poor neurological outcomes following out-of-hospital cardiac arrest using neuron-specific enolase and neurofilament light chain in patients with and without haemolysis.

Hypoxic-ischaemic brain injury following out-of-hospital cardiac arrest (OHCA) is a common complication and a major cause of death. Neuron-specific enolase (NSE) and neurofilament light chain (NfL) are released after brain injury and elevated concentrations of both are associated with poor neurological outcome. We explored the influence of haemolysis on the prognostic performance of NSE and NfL. The study is based on post hoc analyses of a randomized, single-centre, double-blinded, controlled trial (IMICA), where comatose OHCA patients of presumed cardiac cause were included. Free-haemoglobin was measured at admission to quantify haemolysis. NSE and NfL were measured after 48 h to estimate the extent of brain injury. Montreal Cognitive Assessment score (MoCA) was assessed to evaluate neurocognitive impairments. Seventy-three patients were included and divided into two groups by the median free-haemoglobin at admission. No group differences in mortality or poor neurological outcome were observed. The high-admission free-haemoglobin group had a significantly higher concentration of NSE compared to the low-admission free-haemoglobin group (27.4 µmol/L vs. 19.6 µmol/L, P = 0.03), but no differences in NfL. The performance of NSE and NfL in predicting poor neurological outcome were high for both, but NfL was numerically higher [area under the ROC (AUROC) 0.90 vs. 0.96, P = 0.09]. Furthermore, NfL, but not NSE, was inversely correlated with MoCA score, R2 = 0.21, P = 0.006. High free-haemoglobin at admission was associated with higher NSE concentration after 48 h, but, the performance of NSE and NfL in predicting poor neurological outcome among OHCA patients were good regardless of early haemolysis. Only elevated NfL concentrations were associated with cognitive impairments.

Calcitonin gene-related peptide inhibits neuronal apoptosis in heatstroke rats via PKA/p-CREB pathway

PurposeThe incidence of heatstroke (HS) is not particularly high; however, once it occurs, the consequences are serious. It is reported that calcitonin gene-related peptide (CGRP) is protective against brain injury in HS rats, but detailed molecular mechanisms need to be further investigated. In this study, we further explored whether CGRP inhibited neuronal apoptosis in HS rats via protein kinase A (PKA)/p-cAMP response element-binding protein (p-CREB) pathway. MethodsWe established a HS rat model in a pre-warmed artificial climate chamber with a temperature of (35.5 ± 0.5) °C and a relative humidity of 60% ± 5%. Heatstress was stopped once core body temperature reaches above 41 °C. A total of 25 rats were randomly divided into 5 groups with 5 animals each: control group, HS group, HS+CGRP group, HS+CGRP antagonist (CGRP8-37) group, and HS+CGRP+PKA/p-CREB pathway blocker (H89) group. A bolus injection of CGRP was administered to each rat in HS+CGRP group, CGRP8-37 (antagonist of CGRP) in HS+CGRP8-37 group, and CGRP with H89 in HS+CGRP+H89 group. Electroencephalograms were recorded and the serum concentration of S100B, neuron-specific enolase (NSE), neuron apoptosis, activated caspase-3 and CGRP expression, as well as pathological morphology of brain tissue were detected at 2 h, 6 h, and 24 h after HS in vivo. The expression of PKA, p-CREB, and Bcl-2 in rat neurons were also detected at 2 h after HS in vitro. Exogenous CGRP, CGRP8-37, or H89 were used to determine whether CGRP plays a protective role in brain injury via PKA/p-CREB pathway. The unpaired t-test was used between the 2 samples, and the mean ± SD was used for multiple samples. Double-tailed p < 0.05 was considered statistically significant. ResultsElectroencephalogram showed significant alteration of θ (54.50 ± 11.51 vs. 31.30 ± 8.71, F = 6.790, p = 0.005) and α wave (16.60 ± 3.21 vs. 35.40 ± 11.28, F = 4.549, p = 0.020) in HS group compared to the control group 2 h after HS. The results of triphosphate gap terminal labeling (TUNEL) showed that the neuronal apoptosis of HS rats was increased in the cortex (9.67 ± 3.16 vs. 1.80 ± 1.10, F = 11.002, p = 0.001) and hippocampus (15.73 ± 8.92 vs. 2.00 ± 1.00, F = 4.089, p = 0.028), the expression of activated caspase-3 was increased in the cortex (61.76 ± 25.13 vs. 19.57 ± 17.88, F = 5.695, p = 0.009) and hippocampus (58.60 ± 23.30 vs. 17.80 ± 17.62, F = 4.628, p = 0.019); meanwhile the expression of serum NSE (5.77 ± 1.78 vs. 2.35 ± 0.56, F = 5.174, p = 0.013) and S100B (2.86 ± 0.69 vs. 1.35 ± 0.34, F = 10.982, p = 0.001) were increased significantly under HS. Exogenous CGRP decreased the concentrations of NSE and S100B, and activated the expression of caspase-3 (0.41 ± 0.09 vs. 0.23 ± 0.04, F = 32.387, p < 0.001) under HS; while CGRP8-37 increased NSE (3.99 ± 0.47 vs. 2.40 ± 0.50, F = 11.991, p = 0.000) and S100B (2.19 ± 0.43 vs. 1.42 ± 0.30, F = 4.078, p = 0.025), and activated the expression caspase-3 (0.79 ± 0.10 vs. 0.23 ± 0.04, F = 32.387, p < 0.001). For the cell experiment, CGRP increased Bcl-2 (2.01 ± 0.73 vs. 2.15 ± 0.74, F = 8.993, p < 0.001), PKA (0.88 ± 0.08 vs. 0.37 ± 0.14, F = 20.370, p < 0.001), and p-CREB (0.87 ± 0.13 vs. 0.29 ± 0.10, F = 16.759, p < 0.001) levels; while H89, a blocker of the PKA/p-CREB pathway reversed the expression. ConclusionsCGRP can protect against HS-induced neuron apoptosis via PKA/p-CREB pathway and reduce activation of caspase-3 by regulating Bcl-2. Thus CGRP may be a new target for the treatment of brain injury in HS.