lncRNA H19 Aggravates Brain Injury in Rats following Experimental Intracerebral Hemorrhage via NF-κB Pathway

Objective. To explore the effect of long noncoding RNA H19 (lncRNA H19) on brain injury in rats following experimental intracerebral hemorrhage (ICH). Methods. Rat ICH model was established with type IV collagenase. The neurological function scores were evaluated, and the water content in brain tissue was measured. The nerve injury indexes, inflammatory factors, and oxidative stress indexes were also measured. Moreover, the expression of lncRNA H19 was determined by qRT-PCR, and Western blot detected NF-κB pathway-related protein expression. Results. Compared with the sham group, the neurological function scores, the water content in brain tissue, and levels of injury indicators myelin basic protein (MBP), S-100B, and neuron-specific enolase (NSE) in the ICH rats were significantly increased. Meanwhile, the levels of TNF-α, IL-6, IL-1β, ROS, and MDA were significantly increased, but the levels of SOD were significantly decreased. In addition, the expression of lncRNA H19 in the brain tissue in the ICH group was significantly higher than that in the sham group. After further interference with lncRNA H19 expression (sh-H19 group), the levels of all the above indicators were reversed and the neurological damage was improved. Western blot results showed that the expression of NF-κBp65 and IKKβ was significantly higher, and IκBα expression was lower in the perivascular hematoma tissue in the ICH group compared with the sham group. Compared with the sh-NC group, NF-κBp65 and IKKβ expression were significantly lower and IκBα was significantly higher in the sh-H19 group. Conclusion. lncRNA H19 exacerbated brain injury in rats with ICH by promoting neurological impairment, brain edema, and releasing inflammatory responses and oxidative stress. This may be related to the activation of NF-κB signaling pathway.

Clinical Significance of Tumor Markers for Advanced Thymic Carcinoma: A Retrospective Analysis from the NEJ023 Study

The optimal tumor marker for predicting the prognosis of advanced thymic carcinoma (ATC) remains unclear. We conducted a multi-institutional retrospective study of patients with ATC. A total of 286 patients were treated with chemotherapy. Clinicopathological information, including serum tumor markers, was evaluated to determine the overall survival (OS) and progression-free survival (PFS). The carcinoembryonic antigen, cytokeratin-19 fragment, squamous cell carcinoma (SCC) antigen, progastrin-releasing peptide, neuron-specific enolase (NSE), and alpha-fetoprotein levels were evaluated. In the Kaplan–Meier analysis, the OS was significantly shorter in the patients with elevated NSE levels than in those with normal NSE levels (median, 20.3 vs. 36.8 months; log-rank test p = 0.029; hazard ratio (HR), 1.55; 95% confidence interval (CI), 1.05–2.31 (Cox proportional hazard model)); a similar tendency regarding the PFS was observed (median, 6.4 vs. 11.0 months; log-rank test p = 0.001; HR, 2.04; 95% CI, 1.31–3.18). No significant differences in the OS and PFS were observed among the other tumor markers. In both univariate and multivariate analyses of the patients with SCC only, the NSE level was associated with the OS and PFS. Thus, the NSE level may be a prognostic tumor marker for thymic carcinoma, regardless of histology.

Total Protein–Chloride Ratio in Pleural Fluid Independently Predicts Overall Survival in Malignant Pleural Effusion at the First Diagnosis

ObjectivePre-treatment biomarkers to estimate overall survival (OS) for malignant pleural effusion (MPE) are unidentified, especially those in pleural fluid. We evaluated the relationship between OS and total protein–chloride ratio in malignant pleural effusion (PE TPClR).Materials and MethodsA retrospective study was undertaken to identify patients from 2006 to 2018 who had pathologically or cytologically confirmed MPE and received no tumor-targeted therapy. We recorded the pre-treatment clinicopathologic characteristics and follow-up status. OS was estimated by the Kaplan–Meier method, and the association between variables and OS was evaluated by Cox proportional hazards models.ResultsWe screened 214 patients who met the eligibility criteria. The optimal cutoff value for the PE TPClR was set at 0.53. The univariate analysis showed that there was a significant correlation between PE TPClR and OS (P < 0.001). The multivariate analysis between OS and the variables selected from the univariate analysis showed that the levels of neutrophil, alkaline phosphatase, neuron-specific enolase, platelets, albumin in peripheral blood, and white blood cells in pleural effusion were also independent predictors of OS.ConclusionIn patients with MPE, pre-treatment PE TPClR independently predicts OS. Although further research is necessary to generalize our results, this information will help clinicians and patients to determine the most appropriate treatment for MPE patients.

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 Pathophysiological Aspects of Cerebral Diseases

Introduction. Cerebrovascular disorders are the main causes of heavy burden health worldwide, also, it is critical to understand the pathophysiological mechanism and then trying to prevent the neurological sequels. Objective. To discuss the inflammatory and oxidative stress aspects associated to the cerebrovascular diseases, focusing on biomarkers, also the role of omega oils, and the intracellular molecular network associated to the tissue burden on those conditions. Results. One of the most promising biomarkers it is Neuron-Specific Enolase (NSE). Serum NSE levels were elevated in stroke-patients compared to the non-stroke controls. Also, studies have demonstrated that in specific ratio omega oils 3, 6 and 9 can ameliorate the inflammatory and oxidative stress in nervous tissue and could be useful to the inflammatory and oxidative stress negative effects of cerebrovascular diseases. In addition, the study of the molecular mechanisms is essential to understand which molecules could be addressed in cascade of events preventing the permanent damage on the nervous tissue. Final considerations. The studies on cerebrovascular disorders must precisely identify the mechanisms and key molecules involved and improve the time of diagnostics and prognostics reducing the negative impacts of those conditions.

Neurometabolic Therapy in Patients with Encephalopathy Associated with COVID-19

The objective: to evaluate the effectiveness of neurometabolic therapy in patients with severe course of the new coronavirus infection of COVID-19 complicated by the development of encephalopathy.Subjects and Methods. A pilot prospective study was carried out with the participation of 61 patients with a severe course of COVID-19 complicated by encephalopathy. The patients were randomized into two groups: the study group (n = 34), the patients in which, in contrast to the control group (n = 27), received Cytoflavin in addition to the main therapy in a daily dose of up to 40 ml for 5 days. The dynamics of the general and neurological status was assessed on days 3‒4 and 6‒7 days of treatment using the NEWS (National Early Warning Score), Glasgow coma and ICDSC (Intensive Care Delirium Screening Checklist) scales. Additionally, the blood level of neuron-specific enolase (NSE) was investigated at baseline and on days 6‒7.Results. Patients in most cases were elderly or senile with a high comorbidity index (up to 4 points according to Charlson). The persistence of delirious symptoms correlated with their age and low SpO2 levels. In half of the cases (50.8%), the disease had an unfavorable outcome. In the study group, by the 6‒7th day of treatment, there was a significant positive dynamics of the general condition, assessed by the NEWS scale (p = 0.012), a tendency towards a faster recovery of the overall score on the Glasgow scale (p = 0.083), a tendency towards more rapid regression of delirious symptoms by ICDSC scale (p = 0.055) versus the comparison group.Conclusions. Given the high risk of an unfavorable outcome in patients with a severe course of COVID-19 complicated by the development of encephalopathy, the additional use of Cytoflavin is advisable since it contributes to the regression of the symptoms of encephalopathy and may have a positive effect on the course of the disease.

Neural Function Recovery and Safety of Mild Hypothermia Therapy Combined with Monosialotetrahexosylganglioside on Neonatal Asphyxia Complicated by Hypoxic Ischemic Encephalopathy

Objective. To explore the effect and safety of mild hypothermia therapy combined with monosialotetrahexosylganglioside (GM1) on neural function recovery of neonatal asphyxia complicated by hypoxic ischemic encephalopathy (HIE). Methods. The clinical data of 90 neonates with HIE were retrospectively analyzed. According to the treatment methods, the neonates were divided into a routine group, a mild hypothermia group, and a combination group, with 30 cases in each group. The differences in neural function recovery, biochemical indexes, clinical signs recovery, efficacy, and complications were observed in the three groups after treatment. Results. After treatment, the score of neonatal behavioral neurological assessment (NBNA) and level of superoxide dismutase (SOD) in the combination group were higher than those of the other two groups ( P < 0.05 ). The levels of neuron-specific enolase (NSE), S-100β protein, and plasma neuropeptide Y (NPY) in the combination group were lower than those in the other two groups, and the recovery time of consciousness, muscle tension, and reflex was shorter ( P < 0.05 ). The combination group showed higher total effective rate and lower incidence of complications as compared with the other two groups ( P < 0.05 ). Conclusion. Mild hypothermia therapy combined with GM1 for the treatment of neonatal asphyxia complicated by HIE can promote the recovery of neural function and reduce the incidence of complications in neonates.

Low Doses of Imidacloprid Induce Oxidative Stress and Neural Cell Disruption in Earthworm Eisenia fetida

Imidacloprid is a widely used pesticide that belongs to the class of neonicotinoids. There is a piece of rising evidence that neonicotinoids exert cytotoxic effects in non-target organisms including vertebrate species such as mammals. Nevertheless, dose-limiting toxicity and molecular mechanisms of neonicotinoids' deleterious effects are still poorly understood. In accord to imidacloprid fate in the environment, the most of used pesticide is absorbed in the soil. Therefore, earthworms, which are prevailing soil organisms, could be considered as a target of neonicotinoids toxicity. The earthworm’s simple nervous system is a prospective model for neurotoxicological studies. We exposed earthworms to imidacloprid in a paper contact test with a doses range of 0.1‑0.4 µg/cm2 for 14 days. In the present work, we studied the imidacloprid effect on oxidative stress generation and neuronal marker neuron-specific enolase (NSE) expression. The exposure to imidacloprid induced a dose-dependent decrease in NSE. Both reactive oxygen species production and lipid peroxidation level were upregulated as well. Observed NSE decline suggests imidacloprid-caused disturbance in earthworm neuron cells. Obtained data have shown that relatively low doses of imidacloprid are potent to induce cytotoxicity in neurons. Furthermore, neurotoxicity could be recognized as one of an individual scenario of the general imidacloprid toxicity. Thus, presented results suggest the cytotoxicity of imidacloprid low doses in non-target organisms and hypothesize that NSE downregulation could be estimated as a biomarker of neonicotinoid cytotoxicity in a nervous system of non-insect species.