Expression Of Neuron-specific Enolase Research Articles

Research progress of neuron-specific enolase in cognitive disorder: a mini review.

Numerous studies have demonstrated that neuron-specific enolase (NSE) serves as a distinctive indicator of neuronal injury, with its concentration in blood reflecting the extent and magnitude of nervous system damage, and the expression of serum NSE is correlated with cognitive dysfunction. The assessment of NSE holds significant importance in diagnosing cognitive dysfunction, assessing disease severity, predicting prognosis, and guiding treatment. In this review, the research progress of NSE in cognitive dysfunction was reviewed, and the value of serum NSE level in predicting disease severity and prognosis of patients with cognitive dysfunction was discussed.

Lipid peroxidation-induced ferroptosis as a therapeutic target for mitigating neuronal injury and inflammation in sepsis-associated encephalopathy: insights into the hippocampal PEBP-1/15-LOX/GPX4 pathway

BackgroundSepsis-associated encephalopathy (SAE) refers to the widespread impairment of brain function caused by noncentral nervous system infection mediated by sepsis. Lipid peroxidation-induced ferroptosis contributes to the occurrence and course of SAE. This study aimed to investigate the relationship between neuronal injury and lipid peroxidation-induced ferroptosis in SAE.MethodsBaseline data were collected from pediatric patients upon admission, and the expression levels of various markers related to lipid peroxidation and ferroptosis were monitored in the serum and peripheral blood mononuclear cells (PBMCs) of patients with SAE as well as SAE model mice. The hippocampal phosphatidylethanolamine-binding protein (PEBP)-1/15-lysine oxidase (LOX)/ glutathione peroxidase 4 (GPX4) pathway was assessed for its role on the inhibitory effect of ferroptosis in SAE treatment.ResultsThe results showed elevated levels of S100 calcium-binding protein beta (S-100β), glial fibrillary acidic protein, and malondialdehyde in the serum of SAE patients, while superoxide dismutase levels were reduced. Furthermore, analysis of PBMCs revealed increased transcription levels of PEBP1, LOX, and long-chain fatty acyl-CoA synthetase family member 4 (ACSL4) in SAE patients, while the transcription levels of GPX4 and cystine/glutamate transporter xCT (SLC7A11) were decreased. In comparison to the control group, the SAE mice exhibited increased expression of S-100β and neuron-specific enolase (NSE) in the hippocampus, whereas the expression of S-100β and NSE were reduced in deferoxamine (DFO) mice. Additionally, iron accumulation was observed in the hippocampus of SAE mice, while the iron ion levels were reduced in the DFO mice. Inhibition of ferroptosis alleviated the mitochondrial damage (as assessed by transmission electron microscopy, hippocampal mitochondrial ATP detection, and the JC-1 polymer-to-monomer ratio in the hippocampus) and the oxidative stress response induced by SAE as well as attenuated neuroinflammatory reactions. Further investigations revealed that the mechanism underlying the inhibitory effect of ferroptosis in SAE treatment is associated with the hippocampal PEBP-1/15-LOX/GPX4 pathway.ConclusionThese results offer potential therapeutic targets for the management of neuronal injury in SAE and valuable insights into the potential mechanisms of ferroptosis in neurological disorders.

Endoplasmic reticulum stress and death receptor-mediated apoptosis in the neuronal differentiation of adult adipose-derived stromal cells

Apoptosis is the primary cause of cell death in the differentiation of Adipose-derived stromal cells (ADSCs) into neurons. However, the relationship between endoplasmic reticulum stress (ERS) and death receptor-mediated apoptosis in ADSC-induced neuronal differentiation is not clear. ADSCs were isolated and induced to differentiate into neurons using β-mercaptoethanol. The expression of neuron-specific enolase (NSE), GRP94, CHOP, Fas/FasL, TNFR1/TNF-α, DR5/TRAIL, Caspase8, and Caspase3 in ADSCs was examined using immunocytochemistry and Western blotting before induction, during pre-induction, and after induction. Transmission electron microscopy (TEM) was used to observe changes in the morphology of the endoplasmic reticulum (ER), and the MTT assay was employed to measure cell viability in the uninduced and induced groups. Additionally, the number of apoptotic cells during the induction process was measured using flow cytometry with Annexin V/PI. With increasing induction time, the positive expression rates of CHOP, Fas/FasL, Caspase8, Caspase-3, and NSE gradually increased, while the positive expression rate of GRP94 decreased. TNFR1/TNF-α and DR5/TRAIL peaked at 5 h post-induction and then decreased at 8 h. TEM revealed swelling and expansion of the ER, vacuolar changes, and degranulation in cells. The MTT assay showed a gradual decrease in the absorbance of surviving cells in all groups. Flow cytometry indicated an increasing rate of apoptosis in cells. Therefore, ERS in the normal culture and growth of ADSCs, manifesting as enhanced unfolded protein response (UPR), maintains the normal survival of ADSCs. However, in the process of ADSC-induced differentiation into neurons, ERS and death receptor-mediated apoptosis are significant causes of cell death.

Tumor protein D52 (isoform 3) induces NF-κB – STAT3 mediated EMT driving neuroendocrine differentiation of prostate cancer cells

In prostate cancer (PCa) patients, a proto-oncogene Tumor protein D52 (TPD52) is overexpressed, and it is involved in different cellular functions. In this study, we report that TPD52 expression is positively associated with the emergence of neuroendocrine PCa (NEPC). With overexpression of TPD52 in LNCaP cells, we found neuroendocrine differentiation (NED) of cells in in-vitro and distinct NED features confirmed by NE markers neuron-specific enolase (NSE) and chromogranin A (CHR-A). Further, we investigated the molecular mechanisms involved in TPD52 mediated NED of PCa cells. We found that TPD52 activates the NF- κB – STAT3 axis for the induction of NED in LNCaP cells. Indeed, inhibition of NF-κB – STAT3 attenuated the progression of NED in TPD52 positive LNCaP cells. Importantly, silencing of TPD52 expression or inhibition of NF-κB – STAT3 activity in a neuroendocrine cell line NCI-H660 showed a marked decrease in the expression of NSE and CHR-A, confirming the reversal of the NE properties. Notably, TPD52 overexpression in LNCaP cells induced expression of N-cadherin, Vimentin, ZEB1, and Snail1 indicating that TPD52 positively regulates epithelial to mesenchymal transition (EMT) of PCa cells towards NED. Moreover, silencing of Snail1 in TPD52 positive cells blocked the progression of NED and, in NCI-H660 cells reversed NE properties as expected. Of the few requirements of TPD52, activation of NF-κB – STAT3 is essential for promoting EMT compelling NED of LNCaP cells. Collectively, these results reveal that TPD52 is associated with the progression of NEPC and emphasizes the need for therapeutic targeting of TPD52 in PCa.

Effect of Wnt/β-catenin signaling pathway in neural differentiation of human bone marrow mesenchymal stem cells

To explore the effect of basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and the combination of bFGF and EGF in the neural differentiation of human bone marrow mesenchymal stem cells (hBMSCs), and the role of Wnt/β-catenin signaling pathway in this process. The identified 4th-generation hBMSCs were divided into five groups according to different induction conditions, namely control group (group A), EGF induction group (group B), bFGF induction group (group C), EGF and bFGF combined induction group (group D), and EGF, bFGF, and Dickkopf-related protein 1 (DKK-1) combined induction group (group E). After 7 days of continuous induction, the cell morphology was observed by inverted fluorescence phase contrast microscopy, levels of genes that were related to neural cells [Nestin, neuron-specific enolase (NSE), microtubule-associated protein 2 (MAP-2), and glial fibrillary acidic protein (GFAP)] and key components of the Wnt/β-catenin signaling pathway (β-catenin and Cyclin D1) were detected by RT-PCR, and the levels of proteins that were related to neural cells (Nestin and GFAP) as well as genes that were involved in Wnt/β-catenin signaling pathway [β-catenin, phosphorylation β-catenin (P-β-catenin), Cytoplasmic β-catenin, and Nuclear β-catenin] were explored by cellular immunofluorescence staining and Western blot. When compared to groups A and B, the typical neuro-like cell changes were observed in groups C-E, and most obviously in group D. RT-PCR showed that the relative expressions of Nestin, NSE, and MAP-2 genes in groups C-E, the relative expressions of GFAP gene in groups D and E, the relative expression of NSE gene in group B, the relative expressions of β-catenin gene in groups C and D, and the relative expressions of Cyclin D1 gene in groups B-D significantly increased when compared with group A ( P<0.05). Compared with group E, the relative expressions of Nestin, NSE, MAP-2, GFAP, β-catenin, and CyclinD1 genes significantly increased in group D ( P<0.05); compared with group C, the relative expression of Nestin gene in group D significantly decreased ( P<0.05), while NSE, MAP-2, and GFAP genes significantly increased ( P<0.05). The cellular immunofluorescence staining showed that the ratio of NSE- and GFAP-positive cells significantly increased in groups C-E than in group A, in group D than in groups C and E ( P<0.05). Western blot assay showed that the relative expression of NSE protein was significantly higher in groups C and D than in group A and in group D than in groups C and E ( P<0.05). In addition, the relative expression of GFAP protein was significantly higher in groups C-E than in group A and in group D than in group E ( P<0.05). Besides, the relative expressions of β-catenin, Cytoplasmic β-catenin, Nuclear β-catenin, and the ratio of Nuclear β-catenin to Cytoplasmic β-catenin were significantly higher in groups C and D than in group A and in group D than in group E ( P<0.05), whereas the relative expression of P-β-catenin protein was significantly lower in groups C and D than in group A and in group D than in group E ( P<0.05). Different from EGF, bFGF can induce neural differentiation of hBMSCs. In addition, EGF can enhance the hBMSCs neural differentiation of bFGF, while the Wnt/β-catenin signaling pathway may play a positive regulatory role in these processes.

Identification of the potential ferroptosis key genes in lung cancer with bone metastasis.

To identify the potential key genes of ferroptosis in the pathogenesis of lung cancer with bone metastasis (LCBM) by bioinformatics analysis to provide new targets for treating LCBM and an indicator for early monitoring. We first obtained differentially expressed genes (DEGs) associated with ferroptosis from the Gene Expression Omnibus (GEO) database. MiRWalk 2.0 was used to predict the key microRNAs (miRNAs) and construct related gene-miRNA interaction networks. The functional enrichment analysis of key miRNAs was performed using the miEAA database. Finally, the clinical data of 105 lung cancer patients were retrospectively analyzed, and logistic regression analysis was conducted to assess the relationship between serum alkaline phosphatase (ALP), neuron-specific enolase (NSE), and bone metastasis in lung cancer patients, and a receiver operating characteristic (ROC) curve was drawn. We identified 15 ferroptosis-related genes that were differentially expressed in lung cancer bone metastasis. GO and KEGG enrichment analyses suggested that these genes may affect the oxidative stress response, hypoxia response, rough endoplasmic reticulum, mitochondrial outer membrane, iron-sulfur cluster binding, virus receptor activity, central carbon metabolism in cancer, the interleukin-17 (IL-17) signaling pathway, and other aspects to participate in the occurrence and development of lung cancer bone metastasis. Among the 105 lung cancer patients included in the study, 39 cases had bone metastasis, and the incidence rate was 37.14%. A high Eastern Cooperative Oncology Group (ECOG) score and serum ALP and NSE overexpression were associated with bone metastasis in patients with lung cancer. By assessing the risk of bone metastasis in patients with lung cancer, we found that the Area Under Curves (AUCs) of serum ALP and NSE alone and combined were >0.70. The differentially expressed ferroptosis-related genes and predicted miRNA regulatory network in lung cancer bone metastasis and the related functional enrichment analysis provide new targets for the treatment of lung cancer bone metastasis. At the same time, from a serological perspective, it was found that early monitoring of serum ALP and NSE expression in patients with lung cancer could be considered to assess the risk of bone metastasis in the future.

Diagnostic values of glial fibrillary acidic protein, neuron-specific enolase and protein S100β for sepsis-associated encephalopathy

Abstract Background To investigate the expressions of glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE) and protein S100β and their diagnostic values for sepsis-associated encephalopathy (SAE). Methods One hundred patients with sepsis treated from August 2021 to August 2022 were included. They were assigned to a sepsis group (n=65) and an SAE group (n=35), while 50 healthy volunteers physically examined in the same period were enrolled as a control group. The levels of GFAP and NSE were detected by enzyme-linked immunosorbent assay, and that of S100β was determined by transmitted immunoturbidimetric assay. The expressions of GFAP, NSE and S100β in patients with SAE were detected, and their correlations and diagnostic values were analyzed. Results Compared to patients with mild and moderate SAE, those with severe SAE had higher levels of GFAP, NSE and S100β (P&lt;0.05). The levels of GFAP, NSE and S100β were higher in coma patients than those with consciousness disturbance, and they were higher in patients with a poor prognosis than those with a good prognosis (P&lt;0.05). Positive correlations were identified between GFAP and NSE (r=0.573, P=0.001), GFAP and S100β (r=0.468, P=0.005), and NSE and S100β (r=0.540, P=0.001) expression in patients with SAE. Compared with GFAP, NSE and S100β alone, their combination had higher sensitivity and lower specificity for diagnosing SAE (P&lt;0.05). Conclusions There are correlations among GFAP, NSE and S100β, and the combined detection of these three indicators is highly valuable for the diagnosis of SAE.

Synergistic effects of electroacupuncture and bone marrow stromal cells transplantation therapy in ischemic stroke.

Animal studies and clinical trials demonstrated the effectiveness of a combination of transplanted bone marrow stromal cells (BMSC) and electroacupuncture (EA) treatment in improving neurological deficits. However, the ability of the BMSC-EA treatment to enhance brain repair processes or the neuronal plasticity of BMSC in ischemic stroke model is unclear. The purpose of this study was to investigate the neuroprotective effects and neuronal plasticity of BMSC transplantation combined with EA in ischemic stroke. A male Sprague-Dawley (SD) rat middle cerebral artery occlusion (MCAO) model was used. Intracerebral transplantation of BMSC, transfected with lentiviral vectors expressing green fluorescent protein (GFP), was performed using a stereotactic apparatus after modeling. MCAO rats were treated with BMSC injection alone or in combination with EA. After the treatment, proliferation and migration of BMSC were observed in different groups by fluorescence microscopy. Quantitative real-time PCR (qRT-PCR), Western blotting, and immunohistochemistry were performed to examine changes in the levels of neuron-specific enolase (NSE) and nestin in the injured striatum. Epifluorescence microscopy revealed that most BMSC in the cerebrum were lysed; few transplanted BMSC survived, and some living cells migrated to areas around the lesion site. NSE was overexpressed in the striatum of MCAO rats, illustrating the neurological deficits caused by cerebral ischemia-reperfusion. The combination of BMSC transplantation and EA attenuated the expression of NSE, indicating nerve injury repair. Although the qRT-PCR results showed that BMSC-EA treatment elevated nestin RNA expression, less robust responses were observed in other tests. Our results show that the combination treatment significantly improved restoration of neurological deficits in the animal stroke model. However, further studies are required to see if EA could promote the rapid differentiation of BMSC into neural stem cells in the short term.

VEGFA-modified DPSCs combined with LC-YE-PLGA NGCs promote facial nerve injury repair in rats

ObjectiveThe aim of this research was to investigate the effect of vascular endothelial growth factor A (VEGFA)-overexpressing rat dental pulp stem cells (rDPSCs) combined with laminin-coated and yarn-encapsulated poly(l-lactide-co-glycolide) (PLGA) nerve guidance conduit (LC-YE-PLGA NGC) in repairing 10 mm facial nerve injury in rats. Study DesignrDPSCs isolated from rat mandibular central incisor were cultured and identified in vitro and further transfected with the lentiviral vectors (Lv-VEGFA). To investigate the role and mechanisms of VEGFA in neurogenic differentiation in vitro, semaxanib (SU5416), Cell Counting Kit-8 (CCK-8), real-time quantitative polymerase chain reaction (qPCR) and Western blotting were performed. Ten-millimeter facial nerve defect models in rats were established and bridged by LC-YE-PLGA NGCs. The repair effects were detected by transmission electron microscopy (TEM), compound muscle action potential (CMAP), immunohistochemistry and immunofluorescence. ResultsExtracted cells exhibited spindle-shaped morphology, presented typical markers (CD44+CD90+CD34−CD45−), and presented multidirectional differentiation potential. The DPSCs with VEGFA overexpression were constructed successfully. VEGFA enhanced the proliferation and neural differentiation ability of rDPSCs, and the expression of neuron-specific enolase (NSE) and βIII-tubulin was increased. However, these trends were reversed with the addition of SU5416. This suggests that VEGFA mediates the above effects mainly through vascular endothelial growth factor receptor 2 (VEGFR2) binding. The LC-YE-NGC basically meet the requirements of facial nerve repair. For the in vivo experiment, the CMAP latency period was shorter in DPSCS-VEGFA-NGC group in comparison with other experimental groups, while the amplitude was increased. Such functional recovery correlated well with an increase in histological improvement. Further study suggested that VEGFA-modified DPSCs could increase the myelin number, thickness and axon diameter of facial nerve. NSE, βIII-tubulin and S100 fluorescence intensity and immunohistochemical staining intensity were significantly enhanced. ConclusionVEGFA-modified rDPSCs combined with LC-YE-PLGA NGCs have certain advantages in the growth and functional recovery of facial nerves in rats.

Brain damage serum biomarkers induced by COVID-19 in patients from northeast Brazil.

Neurological symptoms have been often reported in COVID-19 disease. In the present study, we evaluated brain damage associated with the increase of serum levels of neurological biomarkers S100B and neuron-specific enolase (NSE) induced by SARS-CoV-2 infection, in a population from Northeastern Brazil. Thirty-six healthy control (G1) individuals and 141 patients with confirmed COVID-19 were enrolled in this study. Positive-COVID-19 patients were divided into two groups according to the severity of illness by the National Institute of Health (NIH) criteria, 76 patients with mild symptoms for COVID-19 and (G2) and 65 with acute respiratory conditions requiring supplemental oxygenation via intensive care unit (ICU) admission (G3). A follow-up study was conducted with 23 patients from G2 14 (D14) and 21 (D21) days after the onset of symptoms. Serum levels of NSE and S100B were measured using the enzyme-linked immunoassay method (ELISA). Results revealed a significant positive association between G3 patients and S100B serum expression (p = 0.0403). The serum levels of NSE were also significantly enhanced in the G3 group compared to the control (p < 0.0001) and G2 group (p < 0.0001). In addition, clinical features such as symptoms and oxygenation status were not correlated with NSE or S100B serum expression. The follow-up study demonstrated a decrease over time (21days) in NSE serum expression (p < 0.0001). These results suggest that brain damage is followed by acute virus exposure, with no long-term effects. Future work examining COVID-19 recovery will shed light on chronic neurological damage of SARS-CoV-2 infection.

MRI changes and expressions of neuron-specific enolase and monocyte chemoattractant protein-1 in cerebrospinal fluid in patients with severe herpes simplex virus encephalitis.

The objective of this research was to analyze the MRI changes and the expression of neuron-specific enolase (NSE) and monocyte chemoattractant protein-1 (MCP-1) in cerebrospinal fluid (CSF) of patients with severe herpes simplex encephalitis. For this purpose, 68 patients with severe herpes simplex virus encephalitis diagnosed and treated in our hospital from April 2020 to April 2021 were selected as the study objects of the study group. In addition, 68 healthy people who underwent normal physical examinations in our hospital were selected as the control group at the same time. They were examined by magnetic resonance imaging (MRI) within one week after the study group was enrolled. CSF samples were collected one week after the onset of the disease in the study group and 2-4 days after the first spinal anesthesia in the control group, Enzyme linked immunosorbent assay (ELIEA) was used to detect the expression of NSE and MCP-1 in cerebrospinal fluid of the two groups, and the linear correlation between NSE and MCP-1 were analyzed. Results showed that compared with the control group, the expression of NSE and MCP-1 in the cerebrospinal fluid of the study group increased significantly (P<0.05). The expression of NSE and MCP-1 in patients with severe herpes simplex encephalitis in a coma was significantly higher than that in patients without severe herpes simplex encephalitis in a coma (P<0.05). NSE and MCP-1 were positively correlated (r=0.597, P=0.001). NSE and MCP-1 were risk factors for severe herpes simplex encephalitis, and the difference was statistically significant (P<0.05). In conclusion, magnetic resonance imaging of patients with severe herpes simplex encephalitis is characterized by multiple lesions in the temporal lobe, insula, and frontal lobe base (especially the marginal system involved) with unilateral or bilateral asymmetric distribution, and abnormal high expression of NSE and MCP-1 in the cerebrospinal fluid of such patients, which has important value in the early diagnosis of this disease.

Tetrandrine alleviates inflammation and neuron apoptosis in experimental traumatic brain injury by regulating the IRE1α/JNK/CHOP signal pathway.

The aim of this study was to investigate the therapeutic roles of Tetrandrine (TET) on traumatic brain injury (TBI) and the underlying mechanism. Traumatic injury model of hippocampal neurons and TBI mouse model were established to evaluate the therapeutic effects. The expression of neuron-specific enolase (NSE), Caspase 3, and Caspase 12 was detected by immunofluorescence. The expression of TNF-α, NF-κB, TRAF1, ERS markers (GADD34 and p-PERK), IRE1α, CHOP, JNK, and p-JNK were evaluated by western blot. Flow cytometry was used to determine the apoptosis of neurons. Brain injury was assessed by Garcia score, cerebral water content, and Evan blue extravasation test. Hematoxylin and eosin staining was used to determine the morphological changes of hippocampal tissue. Apoptosis was assessed by TUNEL staining. In traumatic injury model of hippocampal neurons, TET downregulated NSE, TNF-α, NF-κB, TRAF1, GADD34, p-PERK, IRE1α, CHOP, and p-JNK expression. TET reduced Caspase 3 and Caspase 12 cleavage. Apoptosis rate was inhibited by the introduction of TET. TET improved the Garcia neural score, decreased the cerebral water content and Evans blue extravasation, and reduced NSE, TNF-α, NF-κB, TRAF1, IRE1α, CHOP, and p-JNK expression in mice with TBI, which was significantly reversed by Anisomycin, a JNK selective activator. TET alleviated inflammation and neuron apoptosis in experimental TBI by regulating the IRE1α/JNK/CHOP signal pathway.

Paternal preconceptional diet enriched with n-3 polyunsaturated fatty acids affects offspring brain function in mice.

Recent studies demonstrate that paternal nutrition prior to conception may determine offspring development and health through epigenetic modification. This study aims to investigate the effects of paternal supplementation of n-3 polyunsaturated fatty acids (n-3 PUFAs) on the brain development and function, and associated gene imprinting in the offspring. Three to four-week-old male C57BL/6J mice (founder) were fed with an n-3 PUFA-deficient diet (n-3 D), and two n-3 PUFA supplementation diets - a normal n-3 PUFA content diet (n-3 N) and a high n-3 PUFA content diet (n-3 H) for 12 weeks. Then they were mated to 10-week-old virgin female C57BL/6J mice to generate the offspring. The results showed that paternal n-3 PUFA supplementation in preconception reduced the anxiety- and depressive-like behavior, and improved sociability, learning and memory in the offspring, along with increased synaptic number, upregulated expressions of neuron specific enolase, myelin basic protein, glial fibrillary acidic protein, brain-derived neurotrophic factor in the hippocampus and cerebral cortex, and altered expressions of genes associated with mitochondria biogenesis, fusion, fission and autophagy. Furthermore, with paternal n-3 PUFA supplementation, the expression of imprinted gene Snrpn was downregulated both in testes of the founder mice and their offspring, but upregulated in the cerebral cortex and hippocampus, with altered DNA methylation in its differentially methylated region. The data suggest that higher paternal intake of n-3 PUFAs in preconception may help to maintain optimal brain development and function in the offspring, and further raise the possibility of paternal nutritional intervention for mental health issues in subsequent generations.

Hyperbaric oxygen therapy promotes consciousness, cognitive function, and prognosis recovery in patients following traumatic brain injury through various pathways.

ObjectiveThe aim of this study was to investigate the clinical curative effect of hyperbaric oxygen (HBO) treatment and its mechanism in improving dysfunction following traumatic brain injury (TBI).MethodsPatients were enrolled into control and HBO groups. Glasgow coma scale (GCS) and coma recovery scale-revised (CRS-R) scores were used to measure consciousness; the Rancho Los Amigos scale-revised (RLAS-R) score was used to assess cognitive impairment; the Stockholm computed tomography (CT) score, quantitative electroencephalography (QEEG), and biomarkers, including neuron-specific enolase (NSE), S100 calcium-binding protein beta (S100β), glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and vascular endothelial growth factor (VEGF), were used to assess TBI severity. The patients were followed up 6 months after discharge and assessed with the Glasgow outcome scale-extended (GOSE), functional independence measure (FIM), and the disability rating scale (DRS).ResultsThe CRS-R scores were higher in the HBO group than the control group at 10 days after treatment. The RLAS-R scores were higher in the HBO group than the control group at 10 and 20 days after treatment. The Stockholm CT scores were significantly lower in the HBO group than the control group at 10 days after treatment. HBO depressed the (δ + θ)/(α + β) ratio (DTABR) of EEG, with lower δ band relative power and higher α band relative power than those in the control group. At 20 days after treatment, the expression of NSE, S100β, and GFAP in the HBO group was lower than that in controls, whereas the expression of BDNF, NGF, and VEGF in the HBO group was higher than that in controls. Six months after discharge, the HBO group had lower DRS scores and higher FIM and GOSE scores than the control group significantly.ConclusionsHBO may be an effective treatment for patients with TBI to improve consciousness, cognitive function and prognosis through decreasing TBI-induced hematoma volumes, promoting the recovery of EEG rhythm, and modulating the expression of serum NSE, S100β, GFAP, BDNF, NGF, and VEGF.

Study of the mechanism by which MSCs combined with LITUS treatment improve cognitive dysfunction caused by traumatic brain injury

Traumatic brain injury (TBI) substantially affects the quality of life of patients, and an effective therapy is unavailable. Previous studies have shown that mesenchymal stem cells (MSCs) and low-intensity transcranial ultrasound (LITUS) are effective treatments for neurological damage, inflammation, edema and cognitive impairment caused by TBI. However, it is unclear whether the combination of the two treatments exerts an additive effect. In this study, a rat TBI model was established using the controlled cortical impact (CCI) method. Neurological function was assessed by determining the rat modified neurological score (mNSS), and cognitive function was assessed using the Y-maze. Pathological changes in the injured tissue were observed using hematoxylin-eosin (HE) staining and immunohistochemistry (IHC), and western blot was performed to detect the expression levels of Nestin, neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), growth-associated protein-43 (GAP-43), postsynaptic density protein (PSD-95), brain-derived neurotrophic factor (BDNF), tumor necrosis factor-α (TNF-α), and aquaporin-4 (AQP-4). Real-time fluorescence quantitative polymerase chain reaction (RT–PCR) was performed to detect the expression levels of GAP-43, PSD-95, BDNF, TNF-α, and AQP-4 mRNA to investigate whether MSCs combined with LITUS exert an additive therapeutic effect of alleviating the cognitive dysfunction caused by TBI and the possible mechanisms involved. Rats exhibited cognitive dysfunction 28 days after TBI, and MSCs combined with LITUS treatment ameliorated the cognitive deficits caused by TBI via increasing Nestin, NSE, GAP-43, PSD-95, and BDNF expression and attenuating the inflammatory response and edema caused by TBI via reducing TNF-α and AQP-4 expression. According to these results, MSCs combined with LITUS is more effective than MSCs alone for the treatment of TBI, and the mechanism may be the promotion of neuronal proliferation and differentiation, and the attenuation of the inflammatory response and edema, which ameliorates the spatial learning memory impairment caused by TBI. MSCs combined with LITUS treatment represents a new approach for the clinical treatment of patients with TBI.

Expression of Neuron-Specific Enolase and Other Neuroendocrine Markers is Correlated with Prognosis and Response to Therapy in Non-Hodgkin Lymphoma.

Objective Non-Hodgkin lymphoma (NHL) is a common hematological malignancy. There is very little known about the expression of neuroendocrine immunohistochemical markers and their clinical significance in NHL due to the paucity of studies. Our objective was to study the expression of neuroendocrine immunohistochemical markers in NHL and correlate with clinical parameters. Materials and Methods All cases diagnosed as NHL on morphology and immunohistochemistry (World Health Organization, 2016 classification) were included in the study. Immunohistochemistry for neuron-specific enolase (NSE), synaptophysin, and chromogranin A was performed. The results were correlated with clinical parameters and response to chemotherapy. Results A total of 66 cases were included in the study with a male-to-female ratio of 3.1:1. The most frequent subtypes observed were diffuse large B-cell lymphoma not otherwise specified and follicular lymphoma. Among the neuroendocrine markers, positivity was observed only for NSE, whereas the other markers were uniformly negative. It was positive in both B- and T-cell lymphomas and in many different subtypes. No relation with the age and sex of the patients was observed. However, NSE-positive cases, more frequently, presented in the advanced stage as compared with NSE negative (61 vs. 38%). All NSE-positive cases showed remission with chemotherapy. Conclusion Among the neuroendocrine immunohistochemical markers, positivity was observed only for NSE. This isolated positivity suggests cross-binding of NSE antibodies with some other isoenzyme of NSE. NSE positivity was associated with higher stage and better response to therapy. Despite this apparent paradox, it is recommended that NSE should be part of routine immunohistochemical panel for NHL.

Neuron-specific enolase promotes stem cell-like characteristics of small-cell lung cancer by downregulating NBL1 and activating the BMP2/Smad/ID1 pathway

Little is known about the biological functions of neuron-specific enolase (NSE) as a specific biomarker for small-cell lung cancer (SCLC). Herein, we elucidate the effect and mechanism of NSE on SCLC stem cell-like characteristics. Upregulated NSE expression was observed in spheroid cells. The gain-of-function and loss-of-function approaches demonstrated that modulation of NSE positively regulated cell proliferation, drug resistance, spherical clone formation, tumor growth, and stem cell-like characteristics of SCLC cells. Mechanistic studies revealed that NSE might downregulate the expression of neuroblastoma suppressor of tumorigenicity 1 (NBL1) by interacting with NBL1, thereby attenuating the competitive inhibitory effect of NBL1 on BMP2 and enhancing the interaction between BMP2 and BMPR1A; this, in turn, may activate the BMP2/Smad/ID1 pathway and promote SCLC stem cell-like characteristics. Moreover, overexpression of NBL1or knockdown of BMP2 rescued the NSE-induced stem cell-like characteristics. In clinical specimens, NSE expression was positively associated with ALDH1A1 expression and negatively correlated with NBL1 expression. High NSE and ALDH1A1 expressions and low NBL1 expression were correlated with poor prognosis in patients with SCLC. In summary, our study demonstrated that NSE promoted stem cell-like characteristics of SCLC via NBL1 and the activation of the BMP2/Smad/ID1 pathway.

Reduced Concentrations of NSE, S100β, Aβ, and Proinflammatory Cytokines in Elderly Patients Receiving Ultrasound-Guided Combined Lumbar Plexus-Sciatic Nerve Block during Hip Replacement.

Objective The increase of hip fractures is related to the aging of the population, which has caused a huge medical burden in many countries. Hip replacement has been approved as a highly successful surgical intervention for the patients with hip fractures. Different anesthesia choices in the surgical intervention are associated with the prognosis of patients. This study focused on investigating the application of ultrasound-guided combined lumbar plexus-sciatic nerve block in elderly patients with hip fractures. Methods In this retrospective study, 62 elderly patients received combined spinal-epidural anesthesia and 58 elderly patients underwent ultrasound-guided combined lumbar plexus-sciatic nerve block during the surgery. Hemodynamic monitoring including pulse oxygen saturation (SpO2), heart rate and blood pressure, the assessment of pain intensity using Visual Analogue Scale (VAS), cognitive function assessment through Montreal Cognitive Assessment (MoCA) and biomarkers consisting of serum levels of neuron specific-enolase (NSE), S100 beta protein (S100-β), and amyloid beta protein (Aβ), as well as immune function by interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and high sensitivity C-reactive protein (hs-CRP) were detected in this study. Furthermore, length of hospital stay (LOS) and adverse reactions including hematoma, hypotension, nausea, and vomit were analyzed. Results The findings indicated that comparing with the patients receiving combined spinal-epidural anesthesia, those undergoing ultrasound-guided combined lumbar plexus-sciatic nerve block showed significantly lower level of heart rate, higher level of SpO2, and lower level of diastolic pressure and systolic pressure at 5 minutes and 30 minutes after anesthesia and after surgery (P < 0.05), indicated obviously lower VAS score at 12, 24, and 48 hours after surgery (P < 0.05), and revealed higher MoCA score at 12 days after surgery (P < 0.05). A significantly higher level of NSE, S100β, Aβ, IL-6, IL-1β, TNF-α, and hs-CRP was revealed in the two groups receiving different anesthesia methods at 10 days after surgery compared with that before surgery (P < 0.05). However, the patients receiving ultrasound-guided combined lumbar plexus-sciatic nerve block had obviously lower expression of NSE, S100β, Aβ, IL-6, IL-1β, TNF-α, and hs-CRP compared with the group accepting combined spinal-epidural anesthesia (P < 0.05). The two groups indicated no significant difference in incidence of hypotension and vomit, etc. (P < 0.05), but showed remarkable difference referring to total incidence of adverse reactions and LOS (P < 0.05). Conclusion The application of ultrasound-guided combined lumbar plexus-sciatic nerve block in hip replacement contributes to the stability of hemodynamics and alleviation of postoperative pain intensity. It can reduce cognitive and immune impairment of the elderly patients with hip fractures.

Identification of a Glycosyltransferase Signature for Predicting Prognosis and Immune Microenvironment in Neuroblastoma.

Neuroblastoma (NB) is one of the most common solid tumors in children. Glycosyltransferases (GTs) play a crucial role in tumor development and immune escape and have been used as prognostic biomarkers in various tumors. However, the biological functions and prognostic significance of GTs in NB remain poorly understood. The expression data from Gene Expression Omnibus (GEO) and Therapeutically Applicable Research to Generate Effective Treatments (TARGET) were collected as training and testing data. Based on a progression status, differentially expressed GTs were identified. We constructed a GTscore through support vector machine, least absolute shrinkage and selection operator, and Cox regression in NB, which included four prognostic GTs and was an independent prognostic risk factor for NB. Patients in the high GTscore group had an older age, MYCN amplification, advanced International Neuroblastoma Staging System stage, and high risk. Samples with high GTscores revealed high disialoganglioside (GD2) and neuron-specific enolase expression levels. In addition, a lack of immune cell infiltration was observed in the high GTscore group. This GTscore was also associated with the expression of chemokines (CCL2, CXCL9, and CXCL10) and immune checkpoint genes (cytotoxic T-lymphocyte–associated protein 4, granzyme H, and granzyme K). A low GTscore was also linked to an enhanced response to anti–PD-1 immunotherapy in melanoma patients, and one type of tumor was also derived from neuroectodermal cells such as NB. In conclusion, the constructed GTscore revealed the relationship between GT expression and the NB outcome, GD2 phenotype, and immune infiltration and provided novel clues for the prediction of prognosis and immunotherapy response in NB.

The clinical value of EEG monitoring and silver nanoparticles to detect the levels of serum Nesfatin-1, S100β and neuron-specific enolase in evaluating the severity and prognosis of epilepsy

This study aimed to explore the clinical value of electroencephalogram (EEG) monitoring and the use of silver nanoparticles to detect serum levels of Nesfatin-1, S100β and Neuron-specific enolase (NSE) in assessing the severity and prognosis of epilepsy. A total of 54 epilepsy patients treated at our hospital from June 2017 to June 2019 were selected as the epilepsy group, and 54 healthy subjects were selected as the control group. EEG and serum levels of Nesfatin-1, S100β, and NSE in epilepsy patients without seizure and within 1 hour of seizure were ascertained and compared. The Liverpool Seizure Severity Scale (LSSS) score was used to evaluate the severity of epilepsy in patients, and the correlation between EEG findings and serum Nesfatin-1, S100β , and NSE levels was analyzed. ROC analysis was also conducted on the levels of the three factors. The patients were followed up for 1 year, the mortality rate was calculated, and the levels of Nesfatin-1, S100β, and NSE in deceased and non-deceased patients were compared. There were 50 cases (92.6%) with EEG abnormalities in the epilepsy group and 31 cases (57.4%) with epileptic EEGs in the epileptic non-seizure group. There was a significant difference in the proportion of abnormal EEGs between the two groups of epilepsy patients (P &lt;0.05); the biomarker (Nesfatin-1, S100β, and NSE) serum levels were higher in both the non-seizure group and epileptic group than the control group, and the levels in the seizure group were higher than those in the non-seizure group (P &lt; 0.05); seizures in patients with epilepsy were positively correlated with EEG abnormalities and biomarker serum levels. There was, however, no significant correlation between EEG abnormalities and biomarker serum levels. ROC analysis of epilepsy patients and their serum levels of Nesfatin-1, S100β and NSE showed that the area under the curve corresponding to each index was 0.850, 0.881, and 0.868, respectively (P &lt; 0.05). With regards to deceased patients, the proportion with an abnormal EEG was 100% (15/15), which was higher than 41.0% (16/39) of non-deceased patients. Serum levels of biomarkers were also significantly higher than those in non-deceased patients (P &lt; 0.05). Changes in EEG and biomarker serum levels were closely related to the severity of epilepsy. The proportion of patients with abnormal EEGs during seizure periods was higher, and the expression of serum Nesfatin-1, S100β and NSE was also increased, which means they can be used as markers of epilepsy and have an impact on its prognosis