Neuron-specific Enolase Research Articles

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.

A signal amplifying photoelectrochemical immunosensor based on the synergism of Au@CoFe2O4 and CdS/NiCo2O4 for the sensitive detection of neuron-specific enolases

Neuron-specific enolase (NSE), a marker of small cell lung cancer, is over-expressed in patient serum. To reduce the threat of lung cancer to human health and life, a rapid and effective method for the sensitive detection of NSE is necessary. In this study, a sandwich-type photoelectrochemical (PEC) immunosensor for the rapid and sensitive detection of NSE was constructed. To provide a powerful and stable photocurrent signal, the bandgap-matched CdS/NiCo2O4 was used as the substrate material. In addition, Au@CoFe2O4, which can form a step electron transfer mode with NiCo2O4, was proposed for the first time as a second antibody (Ab2) marker to amplify photoelectric signals. The constructed signal-amplified PEC immunosensor showed good linearity in the range of 1 pg/mL − 100 ng/mL with a detection limit as low as 0.24 pg/mL (S/N=3). The constructed PEC immunosensor has shown excellent stability, selectivity, reproducibility, and repeatability. It showed recoveries in the range of 98% − 105% and relative standard deviations (RSD) within 5% in sample analysis. The method proposed in this study is expected to be more widely used in the future for the detection of other disease markers as well as environmental pollutants.

Reticular Heterojunction for Organic Photoelectrochemical Transistor Detection of Neuron-Specific Enolase.

Reticular heterojunctions on the basis of metal-organic frameworks (MOFs) and covalent organic frameworks (COFs) have sparked considerable interest in recent research endeavors, which nevertheless have seldom been studied in optoelectronic biosensing. In this work, its utilization for organic photoelectrochemical transistor (OPECT) detection of the important cancer biomarker of neuron-specific enolase (NSE) is reported. A MOF@COF@CdS quantum dots (QDs) heterojunction is rationally designed to serve as the photogating module against the polymeric channel. Linking with a sandwich complexing event, target-dependent alternation of the photogate is achieved, leading to the changed photoelectric conversion efficiency as indicated by the amplified OPECT signals. The proposed assay demonstrates good analytical performance in detecting NSE, featuring a linear detection range from 0.1pgmL-1 to 100ngmL-1, with a detection limit of 0.033pgmL-1.

Improved diagnostic accuracy with three lung tumor markers compared to six-marker panel.

Combining multiple tumor markers increases sensitivity for lung cancer diagnosis in the cost of false positive. However, some would like to check as many as tumor markers in the fear of missing cancer. We though to propose a panel of fewer tumor markers for lung cancer diagnosis. Patients with suspected lung cancer who simultaneously underwent all six tests [carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA), squamous cell carcinoma-associated antigen (SCC), neuron-specific enolase (NSE), pro-gastrin-releasing peptide (ProGRP), and sialyl Lewis-X antigen (SLX)] were included. Tumor markers with significant impact on the lung cancer in a logistic regression model were included in our panel. Area under the curve (AUC) was compared between our panel and the panel of all six. We included 1,733 [median 72 years, 1,128 men, 605 women, 779 (45%) confirmed lung cancer]. Logistic regression analysis suggested CEA, CYFRA, and NSE were independently associated with the lung cancer diagnosis. The panel of these three tumor markers [AUC =0.656, 95% confidence interval (CI): 0.630-0.682, sensitivity 0.650, specificity 0.662] had better (P<0.001) diagnostic performance than six tumor markers (AUC =0.575, 95% CI: 0.548-0.602, sensitivity 0.829, specificity 0.321). Compared to applying all six markers (at least one marker above the upper limit of normal), the panel with three markers (at least one marker above the upper limit of normal) led to a better predictive value by lowering the risk of false positives.

Correlations of Expression Levels of Lung Cancer Marker Gene Eno2 and Genes of Carcinogenesis and Apoptosis in the Hypothalamus of Mice with Depression-Like Behavior.

We experimentally demonstrated that chronic social stress during the development of a depression-like state enhances lung metastasis and modifies the expression of many carcinogenesis- and apoptosis-related genes in the hypothalamus of mice, including genes involved in lung cancer pathogenesis in humans. Analysis of the expression of genes encoding the major clinical markers of lung cancer in the hypothalamus of mice with depression-like behavior revealed increased expression of the Eno2 gene encoding neuron-specific enolase, a blood marker of lung cancer progression in humans. It was shown that the expression of this gene in the hypothalamus correlated with the expression of many carcinogenesis- and apoptosis-related genes. The discovered phenomenon may have a fundamental significance and requires further studies.

An Integrated Clinical and Computerized Tomography-Based Radiomic Feature Model to Separate Benign from Malignant Pleural Effusion

Introduction: Distinguishing between malignant pleural effusion (MPE) and benign pleural effusion (BPE) poses a challenge in clinical practice. We aimed to construct and validate a combined model integrating radiomic features and clinical factors using computerized tomography (CT) images to differentiate between MPE and BPE. Methods: A retrospective inclusion of 315 patients with pleural effusion (PE) was conducted in this study (training cohort: n = 220; test cohort: n = 95). Radiomic features were extracted from CT images, and the dimensionality reduction and selection processes were carried out to obtain the optimal radiomic features. Logistic regression (LR), support vector machine (SVM), and random forest were employed to construct radiomic models. LR analyses were utilized to identify independent clinical risk factors to develop a clinical model. The combined model was created by integrating the optimal radiomic features with the independent clinical predictive factors. The discriminative ability of each model was assessed by receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA). Results: Out of the total 1,834 radiomic features extracted, 15 optimal radiomic features explicitly related to MPE were picked to develop the radiomic model. Among the radiomic models, the SVM model demonstrated the highest predictive performance [area under the curve (AUC), training cohort: 0.876, test cohort: 0.774]. Six clinically independent predictive factors, including age, effusion laterality, procalcitonin, carcinoembryonic antigen, carbohydrate antigen 125 (CA125), and neuron-specific enolase (NSE), were selected for constructing the clinical model. The combined model (AUC: 0.932, 0.870) exhibited superior discriminative performance in the training and test cohorts compared to the clinical model (AUC: 0.850, 0.820) and the radiomic model (AUC: 0.876, 0.774). The calibration curves and DCA further confirmed the practicality of the combined model. Conclusion: This study presented the development and validation of a combined model for distinguishing MPE and BPE. The combined model was a powerful tool for assisting in the clinical diagnosis of PE patients.

Effect of high-frequency (5Hz) rTMS stimulating left DLPFC combined with galantamine on cognitive impairment after ischemic stroke and serum homocysteine and neuron-specific enolase.

To investigate the efficacy of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) combined with galantamine in patients with cognitive impairment after stroke and its effect on serum homocysteine (Hcy) and neuron-specific enolase (NSE) levels. A total of 90 patients with cognitive impairment after the first ischemic stroke were enrolled. They were randomly divided into rTMS+ cognitive rehabilitation group, Galantamine + cognitive rehabilitation group, and rTMS+ Galantamine + cognitive rehabilitation group. All groups received routine medical treatment and limb rehabilitation treatment. The rTMS stimulation site was the left dorsolateral prefrontal cortex (left DLPFC), the magnetic stimulation frequency was 5 Hz, the magnetic stimulation intensity was 80% of the motor threshold level, and 3,000 pulses were given every day. The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Fugl-Meyer scale, and modified Barthel index, as well as rehabilitation scale and serum NSE and Hcy were evaluated before and after treatment (after 4 weeks). After 4 weeks of treatment, the scores of MMSE, MoCa scale, Fugl-Meyer scale, and modified Barthel index in the three groups were significantly higher than those before treatment (all p < 0.05), while the serum NSE and Hcy levels of the three groups were decreased. rTMS+ Galantamine + cognitive rehabilitation group had higher scale scores, and the difference between the three groups was statistically significant compared with the other two groups (all p < 0.05). Cognitive rehabilitation combined with HF-rTMS and galantamine could improve the cognitive function of patients to the greatest extent, promote the recovery of physical activity, improve the self-care ability of daily life, and effectively reduce the serum HCY and NSE levels in patients with cognitive impairment after stroke. No randomized controlled trials of similar combination treatments have been reported. The better therapeutic effect may be related to the fact that galantamine combined with repetitive transcranial magnetism can activate the brain cholinergic system more extensively, promote brain neural remodeling through long-term potentiation and inhibit local neuroinflammatory responses in brain injury.

Local control and toxicity outcomes following consolidative radiation therapy in patients with high-risk neuroblastoma: a 20-year experience at a single center.

Intensive multimodal treatment can improve survival in patients with high-risk neuroblastoma, and consolidative radiation therapy has contributed to local control. We examined the clinical outcomes of patients who underwent consolidative radiation therapy at our institution. We retrospectively reviewed the records of patients with high-risk neuroblastoma who underwent consolidative radiation therapy from March 2001 to March 2021 at Asan Medical Center. Patients underwent multimodal treatment including high-dose chemotherapy, surgery, stem cell transplantation, and maintenance therapy. Radiation (median, 21.0 Gy; range, 14-36) was administered to the primary site and surrounding lymph nodes. This study included 37 patients, and the median age at diagnosis was 2.8 years (range, 1.3-10.0). Four patients exhibited local failure, and 5-year free-from locoregional failure rate was 88.7%, with a median followup period of 5.7 years. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 59.1% and 83.6%, respectively. Univariate analysis revealed that patients with neuron-specific enolase levels > 100 ng/mL had significantly worse DFS and OS (P = 0.036, 0.048), and patients with no residual disease before radiation therapy showed superior OS (P = 0.029). Furthermore, patients with 11q deletion or 17q gain exhibited poor DFS and OS, respectively (P = 0.021, 0.011). Six patients experienced grade 1 acute toxicity. Late toxicity was confirmed in children with long-term survival, predominantly hypothyroidism and hypogonadism, typically < grade 3, possibly attributed to combination treatment. Four patients experienced late toxicity ≥ grade 3 with chronic kidney disease, growth hormone abnormality, ileus, premature epiphyseal closure, and secondary tumor, and recovered by hospitalization or surgical treatment. In patients with high-risk neuroblastoma, consolidative radiotherapy to the primary tumor site resulted in excellent local control and a tolerable safety profile.

Blood biomarkers for the differentiation between central and peripheral vertigo in the emergency department: a systematic review and meta-analysis.

In patients with acute vestibular syndrome (AVS), differentiating between stroke and nonstroke causes is challenging in the emergency department (ED). Correct diagnosis of vertigo etiology is essential for early optimum treatment and disposition. The aim of this systematic review and meta-analysis was to summarize the published evidence on the potential of blood biomarkers in the diagnosis and differentiation of peripheral from central causes of AVS. A literature search was conducted for studies published until January 1, 2023, in PubMed, Ovid Medline, and EMBASE databases analyzing biomarkers for the differentiation between central and peripheral AVS. The Quality Assessment of Diagnostic Accuracy Studies questionnaire 2 was used for quality assessment. Pooled standardized mean difference and 95% confidence intervals were calculated if a biomarker was reported in two or more studies. Heterogeneity among included studies was investigated using the I2 metric. A total of 17 studies with 859 central and 4844 peripheral causes of acute dizziness or vertigo, and analysis of 61 biomarkers were included. The general laboratory markers creatinine, blood urea nitrogen, albumin, C-reactive protein, glucose, HbA1c, leukocyte counts, and neutrophil counts and the brain-derived biomarkers copeptin, S100 calcium-binding protein β (S100β), and neuron-specific enolase (NSE) significantly differentiated central from peripheral causes of AVS. This systematic review and meta-analysis highlights the potential of generalized inflammatory markers and brain-specific blood protein markers of NSE and S100β as diagnostic biomarkers for central from peripheral differentiation in AVS. These results, as a complement to clinical characteristics, provide guidance for future large-scale diagnostic research, in this challenging ED patient population.

Medical Management of Acute Spinal Cord Injury with Aspiration pneumonia in a Kid

A two-month-old, non-descript female goat kid was brought to the Veterinary Clinical Complex, Veterinary College and Research Institute, Orathanadu, with a history of continuous high-pitched bleating, respiratory distress, and forelimb paresis over the past two days. The animal has appeared lethargic with an abnormal gait. Neurological examination revealed sluggish sensory and motor reflexes in the forelimbs and palpation elicited pain in the thoracic and dorsal spinal areas (C7-T2). Auscultation revealed exaggerated heart sounds and prolonged expiration. Radiographic examination ruled out spinal involvement but revealed left lung consolidation with pulmonary infiltration. Cerebrospinal fluid analysis showed an increase in neuron-specific enolase (NSE). The condition was tentatively diagnosed as acute spinal cord injury with aspiration pneumonia. Inj. Progesterone and intranasal Budesonide were administered along with a Progesterone patch applied to the lateral neck region. Successful medical management led to gradual clinical improvement observed from the seventh day and completely recovered after 15 days of treatment.

Lower versus higher blood pressure targets in comatose patients resuscitated from out-of-hospital cardiac arrest-Protocol for a secondary Bayesian analysis of the box trial.

The management of blood pressure targets during intensive care after out-of-hospital cardiac arrest (OHCA) remains a topic of debate. The blood Pressure and Oxygenation Targets After OHCA (BOX) trial explored the efficacy of two different blood pressure targets in 789 patients during intensive care after OHCA. In the primary frequentist analysis, no statistically significant differences were found for neurological outcome after 90 days. This protocol outlines secondary Bayesian analyses of 365-day all-cause mortality and two secondary outcomes: neurological outcome after 365 days, and plasma neuron-specific enolase, a biomarker of brain injury, after 48 h. We will employ adjusted Bayesian logistic and linear regressions, presenting results as relative and absolute differences with 95% confidence intervals. We will use weakly informative priors for the primary analyses, and skeptical and evidence-based priors (where available) in sensitivity analyses. Exact probabilities for any benefit/harm will be presented for all outcomes, along with probabilities of clinically important benefit/harm (risk differences larger than 2%-points absolute) and no clinically important differences for the binary outcomes. We will assess whether heterogeneity of treatment effects on mortality is present according to lactate at admission, time to return of spontaneous circulation, primary shockable rhythm, age, hypertension, and presence of ST-elevation myocardial infarction. This secondary analysis of the BOX trial aim to complement the primary frequentist analysis by quantifying the probabilities of beneficial or harmful effects of different blood pressure targets. This approach seeks to provide clearer insights for researchers and clinicians into the effectiveness of these blood pressure management strategies in acute medical conditions, particularly focusing on mortality, neurological outcomes, and neuron-specific enolase.

'Evaluation of beta-2-microglobulin and neuron-specific enolase as prognostic factors in patients over 65 years of age with frailty syndrome hospitalized for acute coronary syndrome'.

The aim of the study is to assess the value of beta-2-microglobulin (B2M) and neuron-specific enolase (NSE) as prognostic factors in the population of patients over 65 years of age with frailty hospitalized due to acute coronary syndrome (ACS). Patients aged ≥65 years with ACS were included. Assessment of frailty was carried out using the FRAIL scale. The measurement of NSE and B2M was carried out three times during hospitalization: (1) at the time of admission, (2) on the second day of hospitalization, (3) on the seventh day of hospitalization, or the day of discharge if it was before the seventh day. The primary endpoint was all-cause mortality, and the secondary endpoint was unscheduled rehospitalization. Of the 127 patients, frailty was identified in 39.3%. Multivariate analysis of variance showed significantly higher levels of NSE ( P = 0.012) and B2M ( P < 0.001) in patients with frailty compared to the nonfrail group and significant changes in marker levels during hospitalization - decreased NSE ( P < 0.001) and increased B2M levels ( P < 0.001). Elevated B2M-1 level was an independent marker of the occurrence of frailty [odds ratio (OR), 1.98 (1.09-4.00); P = 0.044], and the optimal cutoff point for the diagnosis of frailty was 2.85 mg/l [area under the curve (AUC), 0.718 (0.632-0.795)] with sensitivity 52% and specificity 84.4% ( P < 0.001). Elevated NSE-3 level was associated with all-cause mortality, and each 1 ng/ml increase in NSE-3 increased the risk of death by 1.07-fold [OR, 1.07 (1.03-1.10]). Meanwhile, elevated B2M-3 level was associated with unscheduled rehospitalization, and each 1 mg/l increase in B2M-3 increased the risk of unscheduled rehospitalization by 1.21-fold [OR, 1.21 (1.03-1.42)]. The Harrell's C-index for all-cause mortality was higher for NSE-3 [0.820 (95% confidence interval {CI}, 0.706-0.934)] compared to frailty assessed by the FRAIL scale [0.715 (95% CI, 0.580-0.850)], which means that additional NSE-3 assessment may improve the prediction of all-cause mortality. However, Uno's C-Statistic analysis showed that the difference was not statistically significant (Pr>chi-square 0.556). Harrell's C-index for unscheduled rehospitalization was higher for frailty assessed by the FRAIL scale compared to B2M-3. Monitoring NSE and B2M marker levels in patients over 65 years of age with frailty and ACS does not provide additional benefits in terms of prognostic ability compared to tests assessing frailty. B2M, assessed upon hospital admission and monitoring NSE and B2M levels during hospitalization may be considered in the diagnosis of frailty and risk stratification in a group of patients for whom currently available frailty diagnostic tools cannot be used.

Early systemic insults following traumatic brain injury: association with biomarker profiles, therapy for intracranial hypertension, and neurological outcomes—an analysis of CENTER-TBI data

PurposeWe analysed the impact of early systemic insults (hypoxemia and hypotension, SIs) on brain injury biomarker profiles, acute care requirements during intensive care unit (ICU) stay, and 6-month outcomes in patients with traumatic brain injury (TBI).MethodsFrom patients recruited to the Collaborative European neurotrauma effectiveness research in TBI (CENTER-TBI) study, we documented the prevalence and risk factors for SIs and analysed their effect on the levels of brain injury biomarkers [S100 calcium-binding protein B (S100B), neuron-specific enolase (NSE), neurofilament light (NfL), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and protein Tau], critical care needs, and 6-month outcomes [Glasgow Outcome Scale Extended (GOSE)].ResultsAmong 1695 TBI patients, 24.5% had SIs: 16.1% had hypoxemia, 15.2% had hypotension, and 6.8% had both. Biomarkers differed by SI category, with higher S100B, Tau, UCH-L1, NSE and NfL values in patients with hypotension or both SIs. The ratio of neural to glial injury (quantified as UCH-L1/GFAP and Tau/GFAP ratios) was higher in patients with hypotension than in those with no SIs or hypoxia alone. At 6 months, 380 patients died (22%), and 759 (45%) had GOSE ≤ 4. Patients who experienced at least one SI had higher mortality than those who did not (31.8% vs. 19%, p < 0.001).ConclusionThough less frequent than previously described, SIs in TBI patients are associated with higher release of neuronal than glial injury biomarkers and with increased requirements for ICU therapies aimed at reducing intracranial hypertension. Hypotension or combined SIs are significantly associated with adverse 6-month outcomes. Current criteria for hypotension may lead to higher biomarker levels and more negative outcomes than those for hypoxemia suggesting a need to revisit pressure targets in the prehospital settings.

Cortisol as a cerebral cortex neurons apoptosis regulator in acute phase of ischemic stroke (clinical and pathological study)

In response to ischemic stroke (IS) a natural activation of the stress-realizing system occurs. The features of this activation influence the outcome of the acute period and the prognosis of recovery and can be adjusted. At the same time, the role of the stress-realizing system in the pathogenesis of IS is still unexplored.Objective: to investigate the effect of peripheral blood cortisol concentration on the regulation of apoptosis of neurons of the cerebral cortex in the acute phase of IS.Material and methods. A prospective clinical and pathological study was performed. It included 9 patients with IS in the left middle cerebral artery territory who were admitted to hospital and died in the hyperacute phase of IS and had no infectious complications, allergic reactions or oncological diseases and who did not undergo thrombolysis. The cerebral cortex was examined. Neuron-specific enolase (NSE), protein 53 (p53), caspase 3, caspase 8, Fas receptor (CD95), and Fas apoptotic inhibitory molecule 2 (FAIM2) were determined on the slices using an indirect immunoperoxidase immunohistochemical staining method. A total of 567 microscopic fields were analysed for the group of patients with IS and 63 fields for the control group (three people). Before death, the blood concentrations of sFas, sFasL, cortisol, adrenocorticotropic hormone, adrenaline and norepinephrine were determined by enzyme immunoassay (the control group consisted of 28 people).Results. Significant correlation was found between the proportion of casp3-positive neurons and the concentration of cortisol in peripheral blood in zones 2 (r=0.263; p&lt;0.01) and 3 (r=0.383; p&lt;0.01). In the 2nd zone, significant negative correlation was found with the concentrations of sFas (r=-0.177; p&lt;0.05) and sFasL (r=-0.164; p&lt;0.05); in the 3rd zone, significant positive correlation was found with the ratio of the concentrations of sFasL and sFas (r=0.240; p&lt;0.01). The proportion of Fas-positive neurons in the cerebral cortex correlated significantly with the concentration of the soluble form of this molecule (for the 1st zone – r=0.222, for the 2nd zone – r=0.438, for the 3rd zone – r=0.289; p&lt;0.01) and the ratio of the concentrations of sFasL and sFas (respectively: r=0.231, r=0.266 and r=0.281; p&lt;0.01) in the peripheral blood.Conclusion. Peripheral blood cortisol concentration is a factor that determines the regulation of apoptosis of neurons in the cerebral cortex in the acute phase of IS.

Pharmacodynamics and mechanism of Erigeron breviscapus granules in the treatment of ischemic stroke in mice by regulating sphingolipid metabolism based on metabolomics

AimErigeron breviscapus (Vant.) Hand.-Mazz. (EB) granules is the extract preparation of EB, with clear curative effect and unclear mechanism. This study intends to systematically explore the specific mechanism of EB granules in the treatment of IS from the metabolic perspective. MethodsThe model of transient middle cerebral artery occlusion (tMCAO) in mice was established by the suture-occluded method. The therapeutic effect of EB granules on tMCAO mice was evaluated by behavioral evaluation, brain water content determination, 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, and levels of lactate dehydrogenase (LDH) and neuron specific enolase (NSE) in serum. In order to screen differential metabolites, non-targeted metabolomics technology was used to detect the metabolites in serum before and after administration. Univariate statistics, multivariate statistics and bioinformatics were used to analyze the changes of metabolites in serum of tMCAO mice. The possible related mechanism of EB granules in treating IS was screened by pathway enrichment analysis, and the preliminary verification was carried out at animal level by enzyme linked immunosorbent assay (ELISA) and western blot (WB). ResultsEB granules could significantly improve behavior of tMCAO mice, reduce brain water content and cerebral infarction volume, improve morphology of brain tissue, reduce the levels of LDH and NSE in serum. A total of 232 differential metabolites were screened, which were mainly enriched in many biological processes such as sphingolipid metabolism. The differential metabolite S1P and its receptors S1PR1 and S1PR2 in sphingolipid metabolism were verified. The results showed that the level of S1P in brain tissue increased and the protein expression of S1PR1 decreased significantly after modeling, and reversed after administration, but there was no significant difference in the protein expression of S1PR2. ConclusionThe therapeutic effects of EB granules may be related to affecting sphingolipid metabolism through regulating S1P/S1PR1.

Recent advance in electrochemical immunosensors for lung cancer biomarkers sensing

Abstract Lung cancer has a high mortality rate largely due to late-stage diagnosis. Detecting protein and genetic biomarkers through electrochemical immunosensors enables non-invasive early diagnosis. This review discusses recent advances in electrochemical immunosensors for detecting clinically relevant lung cancer biomarkers. The use of nanomaterials like graphene, carbon nanotubes, metal nanoparticles, and conducting polymers in sensor fabrication improves electron transfer kinetics, enhances signal transduction, and allows higher antibody loading. Smart surface immobilization strategies optimize antibody orientation and binding capacity. Amplification approaches utilizing nanomaterials, enzymes, polymers, dendrimers, and DNA nanostructures are applied to enhance output signal per binding event. Various electroanalytical techniques including amperometry, potentiometry, impedance spectroscopy, and voltammetry are employed for quantitative monitoring. Recent immunosensors showcase low detection limits and wide linear ranges for measurement of major biomarkers like carcinoembryonic antigen, neuron specific enolase, and cytokeratin fragment 21-1. Emerging biomarkers such as microRNAs and circulating tumor cells have also been targeted. However, reproducibility, selectivity, multiplexing, and integration with point-of-care platforms need improvement for widespread clinical translation. Overall, electrochemical immunosensors hold immense potential for sensitive, affordable lung cancer diagnosis if ongoing efforts can address current limitations.

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.

Delayed CCL23 response is associated with poor outcomes after cardiac arrest

Chemokines, a family of chemotactic cytokines, mediate leukocyte migration to and entrance into inflamed tissue, contributing to the intensity of local inflammation. We performed an analysis of chemokine and immune cell responses to cardiac arrest (CA). Forty-two patients resuscitated from cardiac arrest were analyzed, and twenty-two patients who underwent coronary artery bypass grafting (CABG) surgery were enrolled. Quantitative antibody array, chemokines, and endotoxin quantification were performed using the patients blood. Analysis of CCL23 production in neutrophils obtained from CA patients and injected into immunodeficient mice after CA and cardiopulmonary resuscitation (CPR) were done using flow cytometry. The levels of CCL2, CCL4, and CCL23 are increased in CA patients. Temporal dynamics were different for each chemokine, with early increases in CCL2 and CCL4, followed by a delayed elevation in CCL23 at forty-eight hours after CA. A high level of CCL23 was associated with an increased number of neutrophils, neuron-specific enolase (NSE), worse cerebral performance category (CPC) score, and higher mortality. To investigate the role of neutrophil activation locally in injured brain tissue, we used a mouse model of CA/CPR. CCL23 production was increased in human neutrophils that infiltrated mouse brains compared to those in the peripheral circulation. It is known that an early intense inflammatory response (within hours) is associated with poor outcomes after CA. Our data indicate that late activation of neutrophils in brain tissue may also promote ongoing injury via the production of CCL23 and impair recovery after cardiac arrest.

Association between PET–CT accumulation in the hypothalamic/pituitary regions and neuron-specific enolase/primary tumor in limited-stage small cell lung cancer: a case-controlled retrospective study

BackgroundResearch on the relationship between neuron-specific enolase (NSE) levels and normal organs, particularly the central nervous system, in small cell lung cancer is limited. Therefore, this study aimed to investigate the relationship between positron emission tomography–computed tomography (PET–CT) accumulation at hypothalamic/pituitary regions, tumor activity, and NSE level in limited-stage small cell lung cancer. We retrospectively analyzed patients who were diagnosed with limited-stage small cell lung cancer at Tokyo Medical University Hospital between July 1, 2019, and May 31, 2023, and were treated with chemoradiotherapy or radiotherapy. Leukocytes, erythrocytes, hemoglobin, platelets, total protein, albumin, NSE, and carcinoembryonic antigen were measured in blood samples obtained before treatment initiation. The maximum standardized uptake value (SUVmax), volume, and total lesion glycolysis (TLG) of each hypothalamic /pituitary region, primary tumor, and lymph node metastases were extracted from PET–CT images. The total tumor volume (primary tumor volume plus lymph node metastases volume) and total TLG (primary tumor TLG plus lymph node metastases TLG) were calculated.ResultsThis study included 19 patients (mean age, 70.1 ± 8.8 years; 13 men and 6 women); the pathology in all patients was small cell lung cancer. Patients were classified into two groups according to the NSE reference value (16.3 ng/mL): six patients having NSE level below the reference value and 13 having NSE level above the reference value. The SUVmax in the hypothalamic/pituitary region was 2.95 in the NSE < 16.3 ng/mL group and 4.10 in the NSE > 16.3 ng/mL group, with a statistically significant difference (p = 0.03). The total tumor volume was 17.8 mL in the NSE < 16.3 ng/mL group and 98.9 mL in the NSE > 16.3 ng/mL group, with a statistically significant difference (p < 0.01). A correlation coefficient of r = 0.458 (p = 0.0486) was observed between SUVmax in the hypothalamus/pituitary and NSE level. A correlation coefficient of r = 0.647 (p < 0.01) was also observed between total tumor volume and NSE level. Finally, a correlation coefficient of r = 0.53 (p = 0.01) was observed between hypothalamic/pituitary TLG and primary tumor TLG.ConclusionsThe findings demonstrated a correlation between hypothalamic/pituitary activity and tumor activity, suggesting the prognostic significance of NSE.

Effects of Dexmedetomidine on Cognitive Function, Oxidative Stress and Brain Protection in Patients Undergoing Craniocerebral Surgery

Background: The protective mechanism of dexmedetomidine on the brains of patients undergoing craniocerebral surgery remains unclear. The aim of this study was to examine the impact of dexmedetomidine on cognitive function, oxidative stress, and brain protection in such patients. Methods: Fifty-four patients who underwent craniocerebral surgery at our hospital from January 2020 to June 2023 were retrospectively selected as study subjects. They were divided into two groups: the control group (n = 27) and the study group (n = 27), based on different auxiliary anesthesia protocols. Patients in the study group received dexmedetomidine before anesthesia induction, using a midline intravenous pump to assist anesthesia, while the control group received an equivalent amount of normal saline. The remaining anesthesia induction and maintenance protocols were consistent for both groups. Cognitive function was assessed using the Mini Mental State Examination (MMSE) before and 1 day after surgery for both groups. Oxidative stress indicators, including malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) levels in the serum of both groups, were measured using enzyme-linked immunosorbent assay (ELISA). Additionally, changes in postoperative brain injury indicators, namely neuron-specific enolase (NSE) and central nervous system-specific protein (S100β), were detected and compared in the serum of both groups. Concurrently, postoperative adverse reactions were recorded for both groups. Results: The MMSE scale scores of both groups of patients 24 hours after surgery were significantly lower than those before surgery. However, the MMSE scale scores of the study group patients were notably higher than those in the control group, with a statistically significant difference (p &lt; 0.05). One hour after surgery, the serum levels of MDA, GSH-Px, and SOD in both groups of patients were significantly elevated compared to pre-surgery levels. Yet, the study group exhibited significantly lower levels of MDA, GSH-Px, and SOD in comparison to the control group, and these differences were statistically significant (p &lt; 0.05). The serum levels of NSE and S100β in both groups were markedly higher than preoperative levels 24 hours after surgery. However, the study group demonstrated significantly lower levels of serum NSE and S100β compared to the control group, with a statistically significant difference (p &lt; 0.05). The incidence of postoperative complications in the study group was 7.41% (2/27), indicating a decreasing trend compared to 18.52% (5/27) in the control group. However, this difference did not reach statistical significance (χ2 = 1.477, p = 0.224). Conclusion: Dexmedetomidine-assisted anesthesia in craniocerebral surgery can effectively enhance postoperative cognitive function, mitigate oxidative stress, and facilitate overall postoperative recovery for patients. The intervention exhibits a favorable safety profile with no reported serious adverse reactions, establishing it as a relatively safe and reliable approach.