Search results for: orthotopic brain tumor

Authors: Diea Gamal Abo El-Hassan, Salwa Ahmed Aly, Abdelrahman Mahmoud Abdelgwad

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The major conjugated linoleic acid (CLA) isomers have anticancer effect, especially breast cancer cells, inhibits cell growth and induces cell death. Also, CLA has several health benefits in vivo, including antiatherogenesis, antiobesity, and modulation of immune function. The present study aimed to assess the safety and anticancer effects of milk fat CLA against in vivo Ehrlich ascites carcinoma (EAC) in female Swiss albino mice. This was based on acute toxicity study, detection of the tumor growth, life span of EAC bearing hosts, and simultaneous alterations in the hematological, biochemical, and histopathological profiles. Materials and Methods: One hundred and fifty adult female mice were equally divided into five groups. Groups (1-2) were normal controls, and Groups (3-5) were tumor transplanted mice (TTM) inoculated intraperitoneally with EAC cells (2×106 /0.2 mL). Group (3) was (TTM positive control). Group (4) TTM fed orally on balanced diet supplemented with milk fat CLA (40 mg CLA/kg body weight). Group (5) TTM fed orally on balanced diet supplemented with the same level of CLA 28 days before tumor cells inoculation. Blood samples and specimens from liver and kidney were collected from each group. The effect of milk fat CLA on the growth of tumor, life span of TTM, and simultaneous alterations in the hematological, biochemical, and histopathological profiles were examined. Results: For CLA treated TTM, significant decrease in tumor weight, ascetic volume, viable Ehrlich cells accompanied with increase in life span were observed. Hematological and biochemical profiles reverted to more or less normal levels and histopathology showed minimal effects. Conclusion: The present study proved the safety and anticancer efficiency of milk fat CLA and provides a scientific basis for its medicinal use as anticancer attributable to the additive or synergistic effects of its isomers.

Keywords: anticancer activity, conjugated linoleic acid, Ehrlich ascites carcinoma, % increase in life span, mean survival time, tumor transplanted mice.

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Authors: Vinod Kumar Tewari, Mazhar Husain, Hari Kishan Das Gupta

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Background: Primary or secondary brain death is also accompanied with vasospasm of the perforators other than tissue disruption & further exaggerates the anoxic damage, in the form of neuropraxia. In normal conditions the excitatory impulse propagates as anterograde neurotransmission (ANT) and at the level of synapse, glutamate activates NMDA receptors on postsynaptic membrane. Nitric oxide (NO) is produced by Nitric oxide Synthetase (NOS) in postsynaptic dendride or cell body and travels backwards across a chemical synapse to bind to the axon terminal of a presynaptic neuron for regulation of ANT this process is called as the retrograde neurotransmission (RNT). Thus the primary function of NO is RNT and the purpose of RNT is regulation of chemical neurotransmission at synapse. For this reason, RNT allows neural circuits to create feedback loops. The haem is the ligand binding site of NO receptor (sGC) at presynaptic membrane. The affinity of haem exhibits > 10,000-fold excess for NO than Oxygen (THE 10,000 FOLD EFFECT). In pathological conditions ANT, normal synaptic activity including RNT is absent. NO donors like sodium nitroprusside (SNP) releases NO by activating NOS at the level of postsynaptic area. NO now travels backwards across a chemical synapse to bind to the haem of NO receptor at axon terminal of a presynaptic neuron as in normal condition. NO now acts as impulse generator (at presynaptic membrane) thus bypasses the normal ANT. Also the arteriolar perforators are having Nitric Oxide Synthetase (NOS) at the adventitial side (outer border) on which sodium nitroprusside (SNP) acts; causing release of Nitric Oxide (NO) which vasodilates the perforators causing gush of blood in brain’s tissue and reversal of brain death. Objective: In brain death cases we only think for various transplantations but this study being a pilot study reverses some criteria of brain death by vasodilating the arteriolar perforators. To study the effect of intrathecal sodium nitroprusside (IT SNP) in cases of brain death in which: 1. Retrograde transmission = assessed by the hyperacute timings of reversal 2. The arteriolar perforator vasodilatation caused by NO and the maintenance of reversal of brain death reversal. Methods: 35 year old male, who became brain death after head injury and has not shown any signs of improvement after every maneuver for 6 hours, a single superfusion done by SNP via transoptic canal route for quadrigeminal cistern and cisternal puncture for IV ventricular with SNP done. Results: He showed spontaneous respiration (7 bouts) with TCD studies showing start of pulsations of various branches of common carotid arteries. Conclusions: In future we can give this SNP via transoptic canal route and in IV ventricle before declaring the body to be utilized for transplantations or dead or in broader way we can say that in near future it is possible to revert back from brain death or we have to modify our criterion.

Keywords: brain death, intrathecal sodium nitroprusside, TCD studies, perforators, vasodilatations, retrograde transmission, 10, 000 fold effect

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Authors: S. Kawther, C. Marshall

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Educational neuroscience has the intention of transforming research findings of the underpinning neural processes of learning to educational practices. A main criticism of the field, hitherto, is that less focus has been put on studying the in-progress practical application of these findings. Therefore, this study aims to gain a better understanding of teachers’ perceptions of the practical application and utilization of brain knowledge. This was approached by investigating the answer to 'What are the facilitators and barriers for bringing research from neuroscience to bear on education?'. Following a qualitative design, semi-structured interviews were conducted with 12 teachers who had a proficient course in educational neuroscience. Thematic analysis was performed on the transcribed data applying Braun & Clark’s steps. Findings emerged with four main themes: time, knowledge, teacher’s involvement, and system. These themes revealed that some effective brain-based practices are being engaged in by the teachers. However, the lack of guidance and challenges regarding this implementation were also found. This study discusses findings in light of the development of educational neuroscience implementation.

Keywords: brain-based, educational neuroscience, neuroeducation, neuroscience-informed

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Authors: Aferdita Stroka Koka, Laver Stroka, Juna Musa, Samanda Celaj

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Non-melanoma skin cancers (NMSCs) are the most common human malignancies. About 5.4 million basal and squamous cell skin cancers are diagnosed each year in the US and new cases continue to grow. About eight out of ten of these are basal cell cancers. Squamous cell cancers occur less often. NMSC usually are treatable, but treatment is expensive and can leave scars. In 2019, 167 patients of both sexes suffering from NMSC were treated by traditional medicine. Patients who have been diagnosed with Basal Cell Carcinoma were 122 cases, Squamous Cell Carcinoma 32 cases and both of them 13 cases. Of these,122 cases were ulcerated lesions and 45 unulcerated lesions. All patients were treated with the herbal solution called NILS, which contains extracts of some Albanian plants such as Allium sativum, Jugulans regia and Laurus nobilis. The treatment is done locally, on the surface of the tumor, applying the solution until the tumor mass is destroyed and, after that, giving the necessary time to the wound to make the regeneration that coincides with the complete healing of the wound. We have prepared a collection of photos for each case. Since the first sessions, a shrinkage and reduction of the tumor mass were evident, up to the total disappearance of the lesion at the end of treatment. The normal period of treatment lasted 1 to 2 weeks, depending on the size of the tumor, then take care of it until the closure of the wound, taking the whole process from 1 to 3 months. In 7 patients, the lesion failed to be dominated by treatment and they underwent standard treatment with radiotherapy or surgery, while in 10 patients, the lesion recurred and was treated again. The aim of this survey was to put in evidence the good results obtained by treatment of NMSC with Albanian traditional medicine methods.

Keywords: local treatment, nils, NMSC, traditional medicine

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Authors: Ramandeep Kaur, Gurjit Singh Bhathal

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Cancer diagnosis is very difficult task. Magnetic resonance imaging (MRI) scan is used to produce image of any part of the body and provides an efficient way for diagnosis of cancer or tumor. In existing method, fuzzy clustering mean (FCM) is used for the diagnosis of the tumor. In the proposed method FCM is used to diagnose the cancer of the foot. FCM finds the centroids of the clusters of the foot cancer obtained from MRI images. FCM thresholding result shows the extract region of the cancer. Morphological operations are applied to get extracted region of cancer.

Keywords: magnetic resonance imaging (MRI), fuzzy C mean clustering, segmentation, morphological operations

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Authors: Rehab F. Abdel-Rahman, Sally A. El Awdan, Rehab R. Hegazy, Dina F. Mansour, Hanan A. Ogaly, Marwan Abdelbaset

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Disorders of the cerebral circulation are the leading cause of numerous neurological and psychiatric illnesses. The transient middle cerebral artery occlusion model (MCAO) is considered to be a reliable and reproducible rodent model of cerebral ischemia. The purpose of the current study was to examine the neuroprotective effects of Crocus sativus (saffron) in a rat model of left middle cerebral artery MCAO. Male Wistar rats were anesthetized and subjected to 1 h of MCAO followed by 48 h reperfusion or sham surgery. One group of the ischemia operated animals was kept as left brain ischemia/reperfusion (I/R). Another 2 operated groups received saffron extract (100 or 200 mg/kg, i.p) four times (60 min before the surgery, during the surgery, and on days 1 and 2 after the occlusion). During the experiment, behavioral tests were performed. After 72 h the animals were euthanized and their left brain hemispheres were used in the biochemical, histopathological, and immunohistochemical studies. Saffron administration revealed an improvement in I/R-induced alteration of locomotor balance and coordination ability of rats. Moreover, saffron decreased the brain content of malondialdehyde, nitric oxide, brain natriuretic peptide and vascular endothelial growth factor with significant increase of reduced glutathione. Immunohistochemical evaluation of caspase-3 and Bax protein expression revealed reduction in I/R-enhanced apoptosis in saffron treated rats. In conclusion, saffron treatment decreases ischemic brain injury in association with inhibition of apoptotic and oxidative cell death in a dose dependent manner.

Keywords: caspase-3, cerebral ischemia, Crocus sativus, rats, vascular endothelial growth factor

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Authors: Seokbeen Lim, Gilwon Yoon

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The readiness potential in brain waves is a brain activity related with an intention whose potential arises even before its conscious intention. This study was carried out in order to understand the generation and mechanism of the readiness potential more. The experiment with two subjects was conducted in two ways following the Oddball task protocol. Firstly, auditory stimuli were randomly presented to the subjects. The subject was allowed to press the keyboard with the right index finger only when the subject heard the target stimulus but not the standard stimulus. Secondly, unlike the first one, the auditory stimuli were randomly presented, and the subjects pressed the keyboard in the same manner, but at the same time with grasping action of the left hand. The readiness potential showed up for both of these experiments. In the first Oddball experiment, the readiness potential was detected only when the target stimulus was presented. However, in the second Oddball experiment with the left hand action of grasping something, the readiness potential was detected at the presentation of for both standard and target stimuli. However, detected readiness potentials with the target stimuli were larger than those of the standard stimuli. We found an interesting phenomenon that the readiness potential was able to be detected even the standard stimulus. This indicates that motor-related readiness potentials can be generated only by the intention to move. These results present a new perspective in psychology and brain engineering since subconscious brain action may be prior to conscious recognition of the intention.

Keywords: readiness potential, auditory stimuli, event-related potential, electroencephalography, oddball task

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Authors: Louise Moles, Steve Riley, Sarah D. Lichenstein, Marzieh Babaeianjelodar, Robert Kohler, Annie Cheng, Corey Horien Abigail Greene, Wenjing Luo, Jonathan Ahern, Bohan Xu, Yize Zhao, Chun Chieh Fan, R. Todd Constable, Sarah W. Yip

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Background: Risks for depression are myriad and include both genetic and brain-based factors. However, relationships between these systems are poorly understood, limiting understanding of disease etiology, particularly at the developmental level. Methods: We use a data-driven machine learning approach connectome-based predictive modeling (CPM) to identify functional connectivity signatures associated with polygenic risk scores for depression (DEP-PRS) among youth from the Adolescent Brain and Cognitive Development (ABCD) study across diverse brain states, i.e., during resting state, during affective working memory, during response inhibition, during reward processing. Results: Using 10-fold cross-validation with 100 iterations and permutation testing, CPM identified connectivity signatures of DEP-PRS across all examined brain states (rho’s=0.20-0.27, p’s<.001). Across brain states, DEP-PRS was positively predicted by increased connectivity between frontoparietal and salience networks, increased motor-sensory network connectivity, decreased salience to subcortical connectivity, and decreased subcortical to motor-sensory connectivity. Subsampling analyses demonstrated that model accuracies were robust across random subsamples of N’s=1,000, N’s=500, and N’s=250 but became unstable at N’s=100. Conclusions: These data, for the first time, identify neural networks of polygenic depression risk in a large sample of youth before the onset of significant clinical impairment. Identified networks may be considered potential treatment targets or vulnerability markers for depression risk.

Keywords: genetics, functional connectivity, pre-adolescents, depression

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Authors: Ningning Liu, Gaoding Jia, Yinshan Wang, Haimei Li, Xinian Zuo, Yufeng Wang, Lu Liu, Qiujin Qian

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Background: There has been speculation that a high IQ may not necessarily provide protection against attention deficit hyperactivity disorder (ADHD), and there may be a U-shaped correlation between IQ and ADHD symptoms. However, this speculation has not been validated in the ADHD population in any study so far. Method: We conducted a study with 5,138 children who have been professionally diagnosed with ADHD and have a wide range of IQ levels. General Linear Models were used to determine the optimal model between IQ and ADHD core symptoms with sex and age as covariates. The ADHD symptoms we looked at included the total scores (TO), inattention (IA) and hyperactivity/impulsivity (HI). Wechsler Intelligence scale were used to assess IQ [Full-Scale IQ (FSIQ), Verbal IQ (VIQ), and Performance IQ (PIQ)]. Furthermore, we examined the correlation between IQ and the execution function [Behavior Rating Inventory of Executive Function (BRIEF)], as well as between IQ and brain surface area, to determine if the associations between IQ and ADHD symptoms are reflected in executive functions and brain structure. Results: Consistent with previous research, the results indicated that FSIQ and VIQ both showed a linear negative correlation with the TO and IA scores of ADHD. However, PIQ showed an inverted U-shaped relationship with the TO and HI scores of ADHD, with 103 as the peak point. These findings were also partially reflected in the relationship between IQ and executive functions, as well as IQ and brain surface area. Conclusion: To sum up, the relationship between IQ and ADHD symptoms is not straightforward. Our study confirms long-standing academic hypotheses and finds that PIQ exhibits an inverted U-shaped relationship with ADHD symptoms. This study enhances our understanding of symptoms and behaviors of ADHD with varying IQ characteristics and provides some evidence for targeted clinical intervention.

Keywords: ADHD, IQ, execution function, brain imaging

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Authors: A. Vani, M. N. Mamatha

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Visual signal processing in human beings occurs in the occipital lobe of the brain. The signals that are generated in the brain are universal for all the human beings and they are called Visual Evoked Potential (VEP). Generally, the visually impaired people lose sight because of severe damage to only the eyes natural photo sensors, but the occipital lobe will still be functioning. In this paper, a technique of artificially generating VEP is proposed to enhance the visual ability of the subject. The system uses the electrical photoreceptors to capture image, process the image, to detect and recognize the subject or object. This voltage is further processed and can transmit wirelessly to a BIOMEMS implanted into occipital lobe of the patient’s brain. The proposed BIOMEMS consists of array of electrodes that generate the neuron potential which is similar to VEP of normal people. Thus, the neurons get the visual data from the BioMEMS which helps in generating partial vision or sight for the visually challenged patient. 

Keywords: BioMEMS, neuro-prosthetic, openvibe, visual evoked potential

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Authors: Chang Liang, Weizhi Gong, Yan Zhang

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Purpose: Hepatocellular carcinoma (HCC) is a malignant tumor with a high mortality rate and poor prognosis worldwide. Murine double minute 2 (MDM2) regulates the tumor suppressor p53, increasing cancer risk and accelerating tumor progression. Speckle-type POX virus and zinc finger protein (SPOP), a key of subunit of Cullin-Ring E3 ligase, inhibits tumor genesis and progression by the ubiquitination of its downstream substrates. This study aimed to clarify whether SPOP and MDM2 are mutually regulated in HCC and the correlation between SPOP and MDM2 and the prognosis of HCC patients. Methods: First, the expression of SPOP and MDM2 in HCC tissues were detected by TCGA database. Then, 53 paired samples of HCC tumor and adjacent tissues were collected to evaluate the expression of SPOP and MDM2 using immunohistochemistry. Chi-square test or Fisher’s exact test were used to analyze the relationship between clinicopathological features and the expression levels of SPOP and MDM2. In addition, Kaplan‒Meier curve analysis and log-rank test were used to investigate the effects of SPOP and MDM2 on the survival of HCC patients. Last, the Multivariate Cox proportional risk regression model analyzed whether the different expression levels of SPOP and MDM2 were independent risk factors for the prognosis of HCC patients. Results: Bioinformatics analysis revealed the low expression of SPOP and high expression of MDM2 were related to worse prognosis of HCC patients. The relationship between the expression of SPOP and MDM2 and tumor stem-like features showed an opposite trend. The immunohistochemistry showed the expression of SPOP protein was significantly downregulated while MDM2 protein significantly upregulated in HCC tissue compared to that in para-cancerous tissue. Tumors with low SPOP expression were related to worse T stage and Barcelona Clinic Liver Cancer (BCLC) stage, but tumors with high MDM2 expression were related to worse T stage, M stage, and BCLC stage. Kaplan–Meier curves showed HCC patients with high SPOP expression and low MDM2 expression had better survival than those with low SPOP expression and high MDM2 expression (P < 0.05). A multivariate Cox proportional risk regression model confirmed that a high MDM2 expression level was an independent risk factor for poor prognosis in HCC patients (P <0.05). Conclusion: The expression of SPOP protein was significantly downregulated, while the expression of MDM2 significantly upregulated in HCC. The low expression of SPOP and high expression. of MDM2 were associated with malignant progression and poor prognosis of HCC patients, indicating a potential therapeutic target for HCC patients.

Keywords: hepatocellular carcinoma, murine double minute 2, speckle-type POX virus and zinc finger protein, ubiquitination

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Authors: Lian Zeng

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Double-Spear 1-H2-1 (DS1-H2-1) is an oncolytic virus and an innovative biological drug candidate. The chemical composition of the drug product is a live attenuated West Nile virus (WNV) containing the human T cell costimulator (CD86) gene. After intratumoral injection, the virus can rapidly self-replicate in the injected site and lyse/kill the tumor by repeated infection among tumor cells. We also established xenograft tumor models in mice to evaluate the drug candidate's efficacy on those tumors. The results from preclinical studies on transplanted tumors in immunodeficient mice showed that DS1-H2-1 had significant oncolytic effects on human-origin cancers: it completely (100%) shrieked human glioma; limited human neuroblastoma growth reached as high as 95% growth inhibition rate (%TGITW). The safety data of preclinical animal experiments confirmed that DS1-H2-1 is safe as a biological drug for clinical use. In the preclinical drug efficacy experiment, virus-drug administration with different doses did not show abnormal signs and disease symptoms in more than 300 tested mice, and no side effects or death occurred through various administration routes. Intravenous administration did not cause acute infectious disease or other side effects. However, the replication capacity of the virus in tumor tissue via intravenous administration is only 1% of that of direct intratumoral administration. The direct intratumoral administration of DS1-H2-1 had a higher rate of viral replication. Therefore, choosing direct intratumoral injection can ensure both efficacy and safety.

Keywords: oncolytic virus, WNV-CD86, immunotherapy drugs, glioma, neuroblastoma

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Authors: Amil Suleimanov, Aigul Saduakassova, Denis Vinnikov

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Objective: To assess functional visceral fat (VAT) activity evaluated by ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) as a predictor of metastases in colorectal cancer (CRC). Materials and methods: We assessed 60 patients with histologically confirmed CRC who underwent 18F-FDG PET/CT after a surgical treatment and courses of chemotherapy. Age, histology, stage, and tumor grade were recorded. Functional VAT activity was measured by maximum standardized uptake value (SUVmax) using ¹⁸F-FDG PET/CT and tested as a predictor of later metastases in eight abdominal locations (RE – Epigastric Region, RLH – Left Hypochondriac Region, RRL – Right Lumbar Region, RU – Umbilical Region, RLL – Left Lumbar Region, RRI – Right Inguinal Region, RP – Hypogastric (Pubic) Region, RLI – Left Inguinal Region) and pelvic cavity (P) in the adjusted regression models. We also report the best areas under the curve (AUC) for SUVmax with the corresponding sensitivity (Se) and specificity (Sp). Results: In both adjusted for age regression models and ROC analysis, 18F-FDG accumulation in RLH (cutoff SUVmax 0.74; Se 75%; Sp 61%; AUC 0.668; p = 0.049), RU (cutoff SUVmax 0.78; Se 69%; Sp 61%; AUC 0.679; p = 0.035), RRL (cutoff SUVmax 1.05; Se 69%; Sp 77%; AUC 0.682; p = 0.032) and RRI (cutoff SUVmax 0.85; Se 63%; Sp 61%; AUC 0.672; p = 0.043) could predict later metastases in CRC patients, as opposed to age, sex, primary tumor location, tumor grade and histology. Conclusions: VAT SUVmax is significantly associated with later metastases in CRC patients and can be used as their predictor.

Keywords: ¹⁸F-FDG, PET/CT, colorectal cancer, predictive value

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Authors: Muhammad Faisal Khilji, Rana Shoaib Hamid, Asim Qureshi

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A fifty years old female presented in the emergency department of a tertiary care hospital with complaints of migraine type headache for the last few months. Her last episode of headache was severe, increasing in intensity, associated with nausea but no fever, lasting more than 24 hours and not resolving with analgesics. On examination there was no neurological deficit. CT scan of brain showed a large Pedunculated, non-expansible, non-aggressive bony lesion in the clivus with its sharp fragment impinging into the pons. Findings were further confirmed with MRI brain. Trans-sphenoidal excision biopsy was done and histopathology proved the lesion to be osteochondroma of clivus.

Keywords: osteochondroma, clivus, headache, CT scan

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Authors: Matthew Baucum

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With the increasing popularity of fMRI as an experimental method, psychology and neuroscience can greatly benefit from advanced techniques for summarizing and synthesizing large amounts of data from brain imaging studies. One promising avenue is automated meta-analyses, in which natural language processing methods are used to identify the brain regions consistently associated with certain semantic concepts (e.g. “social”, “reward’) across large corpora of studies. This study builds on this approach by demonstrating how, in fMRI meta-analyses, individual voxels can be treated as vectors in a semantic space and evaluated for their “proximity” to terms of interest. In this technique, a low-dimensional semantic space is built from brain imaging study texts, allowing words in each text to be represented as vectors (where words that frequently appear together are near each other in the semantic space). Consequently, each voxel in a brain mask can be represented as a normalized vector sum of all of the words in the studies that showed activation in that voxel. The entire brain mask can then be visualized in terms of each voxel’s proximity to a given term of interest (e.g., “vision”, “decision making”) or collection of terms (e.g., “theory of mind”, “social”, “agent”), as measured by the cosine similarity between the voxel’s vector and the term vector (or the average of multiple term vectors). Analysis can also proceed in the opposite direction, allowing word cloud visualizations of the nearest semantic neighbors for a given brain region. This approach allows for continuous, fine-grained metrics of voxel-term associations, and relies on state-of-the-art “open vocabulary” methods that go beyond mere word-counts. An analysis of over 11,000 neuroimaging studies from an existing meta-analytic fMRI database demonstrates that this technique can be used to recover known neural bases for multiple psychological functions, suggesting this method’s utility for efficient, high-level meta-analyses of localized brain function. While automated text analytic methods are no replacement for deliberate, manual meta-analyses, they seem to show promise for the efficient aggregation of large bodies of scientific knowledge, at least on a relatively general level.

Keywords: FMRI, machine learning, meta-analysis, text analysis

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Authors: Maria Isabel Garcia-Planas, Maria Victoria Garcia-Camba

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Recent advances in cognitive neuroscience have allowed a step forward in perceiving the processes involved in learning from the point of view of the acquisition of new information or the modification of existing mental content. The evoked potentials technique reveals how basic brain processes interact to achieve adequate and flexible behaviours. The objective of this work, using evoked potentials, is to study if it is possible to distinguish if a patient suffers a specific type of learning disorder to decide the possible therapies to follow. The methodology used, is the analysis of the dynamics of different areas of the brain during a cognitive activity to find the relationships between the different areas analyzed in order to better understand the functioning of neural networks. Also, the latest advances in neuroscience have revealed the existence of different brain activity in the learning process that can be highlighted through the use of non-invasive, innocuous, low-cost and easy-access techniques such as, among others, the evoked potentials that can help to detect early possible neuro-developmental difficulties for their subsequent assessment and cure. From the study of the amplitudes and latencies of the evoked potentials, it is possible to detect brain alterations in the learning process specifically in dyscalculia, to achieve specific corrective measures for the application of personalized psycho pedagogical plans that allow obtaining an optimal integral development of the affected people.

Keywords: dyscalculia, neurodevelopment, evoked potentials, Learning disabilities, neural networks

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Authors: Jaspal Rana, Varinder Singh

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Oxidative stress has been identified as an underlying cause of ischemia-reperfusion (IR) related cognitive dysfunction and brain damage. Therefore, antioxidant based therapies to treat IR injury are being investigated. Allium cepa L. (onion) is used as culinary medicine and is documented to have marked antioxidant effects. Hence, the present study was designed to evaluate the effect of A. cepa outer scale extract (ACE) against IR induced cognition and biochemical deficit in mice. ACE was prepared by maceration with 70% methanol and fractionated into ethylacetate and aqueous fractions. Bilateral common carotid artery occlusion for 10 min, followed by 24 h reperfusion, was used to induce cerebral IR injury. Following IR injury, ACE (100 and 200 mg/kg) was administered orally to animals for 7 days once daily. Behavioral outcomes (memory and sensorimotor functions) were evaluated using Morris water maze and neurological severity score. Cerebral infarct size, brain thiobarbituric acid reactive species, reduced glutathione, and superoxide dismutase activity were also determined. Treatment with ACE significantly ameliorated IR mediated deterioration of memory and sensorimotor functions and rose in brain oxidative stress in animals. The results of the present investigation revealed that ACE improved functional outcomes after cerebral IR injury which may be attributed to its antioxidant properties.

Keywords: allium cepa, cerebral ischemia, memory, sensorimotor

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Authors: Debajyoti Mukherjee, Arathy B. S., Arpita Sahu, Saranga P. Pogula

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A functional model to mimic the functional correctness of a neural network compute accelerator IP is very crucial for design validation. Neural network workloads are based on a Brain Floating Point (BF-16) data type. The major challenge we were facing was the incompatibility of GCC compilers to the BF-16 datatype, which we addressed with a native BF-16 generator integrated into our functional model. Moreover, working with big GEMM (General Matrix Multiplication) or SpMM (Sparse Matrix Multiplication) Work Loads (Dense or Sparse) and debugging the failures related to data integrity is highly painstaking. In this paper, we are addressing the quality challenge of such a complex neural network accelerator design by proposing a functional model-based scoreboard or software model using SystemC. The proposed functional model executes the assembly code based on the ISA of the processor IP, decodes all instructions, and executes as expected to be done by the DUT. The said model would give a lot of visibility and debug capability in the DUT, bringing up micro-steps of execution.

Keywords: ISA, neural network, Brain Float-16, DUT

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Authors: C. Papapicco

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Motherhood is an existential human relationship that lasts for the whole life and is always interwoven with subjectivity and culture. As a result of the brain drain, the motherhood becomes motherhood at distance. Starting from the hypothesis that re-signification of the mother at distance practices is culturally relevant; the research aims to understand the experience of mother at a distance in order to extrapolate the strategies of management of the empty nest. Specifically, the research aims to evaluate the experience of a brain drain’s mother, who created a blog that intends to take care of other parents at a distance. Actually, the blog is the only artifact symbol of the Italian culture of motherhood at distance. In the research, a Netnographic Analysis of the blog mammedicervelliinfuga.com is offered with the aim of understanding if the online world becomes an opportunity to manage the role of mother at a distance. A narrative interview with the blog creator was conducted and then the texts were analyzed by means of a Diatextual Analysis approach. It emerged that the migration projects of talented children take on different meanings and representations for parents. Thus, it is shown that the blog becomes a new form of understanding and practicing motherhood at a distance.

Keywords: brain drain, diatextual analysis, distance motherhood blog, online and offline narrations

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Authors: Olfat Shaker, Miriam Wadie, Reham Ali, Ayman Yosry

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Colorectal cancer (CRC) is a major cause of mortality and morbidity and accounts for over 9% of cancer incidence worldwide. Silent information regulator 2 homolog 1 (SIRT1) gene is located in the nucleus and exert its effects via modulation of histone and non-histone targets. They function in the cell via histone deacetylase (HDAC) and/or adenosine diphosphate ribosyl transferase (ADPRT) enzymatic activity. The aim of this work was to study the relationship between SIRT1 polymorphism and its protein level in colorectal cancer patients in comparison to control cases. This study includes 2 groups: thirty healthy subjects (control group) & one hundred CRC patients. All subjects were subjected to: SIRT-1 serum level was measured by ELISA and gene polymorphisms of rs12778366, rs375891 and rs3740051 were detected by real time PCR. For CRC patients clinical data were collected (size, site of tumor as well as its grading, obesity) CRC patients showed high significant increase in the mean level of serum SIRT-1 compared to control group (P<0.001). Mean serum level of SIRT-1 showed high significant increase in patients with tumor size ≥5 compared to the size < 5 cm (P<0.05). In CRC patients, percentage of T allele of rs12778366 was significantly lower than controls, CC genotype and C allele C of rs 375891 were significantly higher than control group. In CRC patients, the CC genotype of rs12778366, was 75% in rectosigmoid and 25% in cecum & ascending colon. According to tumor size, the percentage of CC genotype was 87.5% in tumor size ≥5 cm. Conclusion: serum level of SIRT-1 and T allele, C allele of rs12778366 and rs 375891 respectively can be used as diagnostic markers for CRC patients.

Keywords: CRC, SIRT1, polymorphisms, ELISA

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Authors: Anjani Kumar Tiwari, Neelam Kumari, Anil Mishra

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The family of phosphodiesterases (PDEs) plays a critical role in control of the level, localization, and duration of intracellular 3’-5’-cyclic adenosine monophosphate (cAMP) and 3’-5’-cyclic guanosine monophosphate (cGMP) signals by specifically hydrolyzing these cyclic nucleotides. As the involvement of cyclic nucleotide second messengers in cell signaling and homeostasis is established, the regulation of these pathways in the brain by various PDE isoforms is an area of considerable interest, as they are involved in nearly all brain functions and in the etiology of neuropsychiatric diseases. The PDE10A isoform, isolated from different species and characterized regarding structure and function, has received much attention in recent years, particularly in the context of schizophrenia and Huntington’s disease, which are both related to a role of PDE10A in the regulation of striatal dopaminergic neurotransmission. Quinazoline analogue 1-(4-methoxyphenyl)-6,7-dimethoxyquinazoline, was evaluated as specific PET marker for phosphodiesterase (PDE) 10A. Here, we report the radiosynthesis of [11C]2 and the in vitro and in vivo evaluation of [11C]2 as a potential positron emission tomography (PET) radiotracer for imaging PDE10A in the central nervous system (CNS). The radiosynthesis of [11C]2 was achieved by O-methylation of the corresponding des-methyl precursor with [11C]methyl iodide. [11C]2 was obtained with ∼50% radiochemical yield. PET imaging studies in rat brain displayed initial specific uptake with very rapid clearance of [11C]2 from brain. Though [11C]2 is not an ideal radioligand for clinical imaging of PDE10A in the CNS. Modified analogue of quinazoline having a higher potency for inhibiting PDE10A and improved pharmacokinetic properties will be necessary for imaging this enzyme with PET.

Keywords: PDE10A, PET, radiotracer, quinazoline

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Authors: A. F. Suleimanov, A. B. Saduakassova, V. S. Pokrovsky, D. V. Vinnikov

Abstract:

Relevance: Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, with relapse occurring in about 70% of advanced cases with poor prognoses. The aim of the study was to evaluate functional visceral fat activity (VAT) evaluated by ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) as a predictor of metastases in epithelial ovarian cancer (EOC). Materials and methods: We assessed 53 patients with histologically confirmed EOC who underwent ¹⁸F-FDG PET/CT after a surgical treatment and courses of chemotherapy. Age, histology, stage, and tumor grade were recorded. Functional VAT activity was measured by maximum standardized uptake value (SUVₘₐₓ) using ¹⁸F-FDG PET/CT and tested as a predictor of later metastases in eight abdominal locations (RE – Epigastric Region, RLH – Left Hypochondriac Region, RRL – Right Lumbar Region, RU – Umbilical Region, RLL – Left Lumbar Region, RRI – Right Inguinal Region, RP – Hypogastric (Pubic) Region, RLI – Left Inguinal Region) and pelvic cavity (P) in the adjusted regression models. We also identified the best areas under the curve (AUC) for SUVₘₐₓ with the corresponding sensitivity (Se) and specificity (Sp). Results: In both adjusted-for regression models and ROC analysis, ¹⁸F-FDG accumulation in RE (cut-off SUVₘₐₓ 1.18; Se 64%; Sp 64%; AUC 0.669; p = 0.035) could predict later metastases in EOC patients, as opposed to age, sex, primary tumor location, tumor grade, and histology. Conclusions: VAT SUVₘₐₓ is significantly associated with later metastases in EOC patients and can be used as their predictor.

Keywords: ¹⁸F-FDG, PET/CT, EOC, predictive value

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Authors: Javad Abdi, Azam Famil Khalili

Abstract:

Modeling emotions have attracted much attention in recent years, both in cognitive psychology and design of artificial systems. However, it is a negative factor in decision-making; emotions have shown to be a strong faculty for making fast satisfying decisions. In this paper, we have adapted a computational model based on the limbic system in the mammalian brain for control engineering applications. Learning in this model based on Temporal Difference (TD) Learning, we applied the proposed controller (termed BELBIC) for a simple model of a submarine. The model was supposed to reach the desired depth underwater. Our results demonstrate excellent control action, disturbance handling, and system parameter robustness for TDBELBIC. The proposal method, regarding the present conditions, the system action in the part and the controlling aims, can control the system in a way that these objectives are attained in the least amount of time and the best way.

Keywords: artificial neural networks, temporal difference, brain emotional learning based intelligent controller, heating- ventilating and air conditioning

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Authors: Forouzan Salehi Fergeni

Abstract:

Converting the movement intents of a person into commands for action employing brain signals like electroencephalogram signals is a brain-computer interface (BCI) system. When left or right-hand motions are imagined, different patterns of brain activity appear, which can be employed as BCI signals for control. To make better the brain-computer interface (BCI) structures, effective and accurate techniques for increasing the classifying precision of motor imagery (MI) based on electroencephalography (EEG) are greatly needed. Subject dependency and non-stationary are two features of EEG signals. So, EEG signals must be effectively processed before being used in BCI applications. In the present study, after applying an 8 to 30 band-pass filter, a car spatial filter is rendered for the purpose of denoising, and then, a method of analysis of variance is used to select more appropriate and informative channels from a category of a large number of different channels. After ordering channels based on their efficiencies, a sequential forward channel selection is employed to choose just a few reliable ones. Features from two domains of time and wavelet are extracted and shortlisted with the help of a statistical technique, namely the t-test. Finally, the selected features are classified with different machine learning and neural network classifiers being k-nearest neighbor, Probabilistic neural network, support-vector-machine, Extreme learning machine, decision tree, Multi-layer perceptron, and linear discriminant analysis with the purpose of comparing their performance in this application. Utilizing a ten-fold cross-validation approach, tests are performed on a motor imagery dataset found in the BCI competition III. Outcomes demonstrated that the SVM classifier got the greatest classification precision of 97% when compared to the other available approaches. The entire investigative findings confirm that the suggested framework is reliable and computationally effective for the construction of BCI systems and surpasses the existing methods.

Keywords: brain-computer interface, channel selection, motor imagery, support-vector-machine

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Authors: Norah Al Hokbany, Ibrahim Al Jammaz, Basem Al Otaibi, Yousif Al Malki, Subhani M. Okarvi

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Objective: The folate receptor is over-expressed in a wide variety of human tumors. Conjugates of folate have been shown to be selectively taken up by tumor cells via the folate receptor. In an attempt to develop new folate radiotracers with favorable biochemical properties for detecting folate receptor-positive cancers. Methods: we synthesized ⁶⁴Cu-NOTA- and ⁶⁴Cu-NOTAM-folate conjugates using a straightforward and simple one-step reaction. Radiochemical yields were greater than 95% (decay-corrected) with a total synthesis time of less than 20 min. Results: Radiochemical purities were always greater than 98% without high-performance liquid chromatography (HPLC) purification. These synthetic approaches hold considerable promise as a rapid and simple method for ⁶⁴Cu-folate conjugate preparation with high radiochemical yield in a short synthesis time. In vitro tests on the KB cell line showed that significant amounts of the radio conjugates were associated with cell fractions. Bio-distribution studies in nude mice bearing human KB xenografts demonstrated a significant tumor uptake and favorable bio-distribution profile for ⁶⁴Cu-NOTA- and ⁶⁴Cu-NOTAM-folate conjugate. The uptake in the tumors was blocked by the excess injection of folic acid, suggesting a receptor-mediated process. Conclusion: These results demonstrate that the ⁶⁴Cu-NOTAM-folate conjugate may be useful as a molecular probe for the detection and staging of folate receptor-positive cancers, such as ovarian cancer and their metastasis, as well as monitoring tumor response to treatment.

Keywords: folate, receptor, tumor imaging, ⁶⁴Cu-NOTA-folate, PET

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Authors: Marawan Abd Elbaset Mohamed, Hanan A. Ogaly, Rehab F. Abdel-Rahman, Ahmed-Farid O.A., Marwa S. Khattab, Reham M. Abd-Elsalam

Abstract:

Liver fibrosis is a severe worldwide health concern due to various chronic liver disorders. Hepatic encephalopathy (HE) is one of its most common complications affecting liver and brain cognitive function. Beta-Carotene (B-Car) is an organic, strongly colored red-orange pigment abundant in fungi, plants, and fruits. The study attempted to know B-Car neuroprotective potential against thioacetamide (TAA)-induced neurotoxicity and cognitive decline in HE in rats. Hepatic encephalopathy was induced by TAA (100 mg/kg, i.p.) three times per week for two weeks. B-Car was given orally (10 or 20 mg/kg) daily for two weeks after TAA injections. Organ body weight ratio, Serum transaminase activities, liver’s antioxidant parameters, ammonia, and liver histopathology were assessed. Also, the brain’s mitogen-activated protein kinase (MAPK), nuclear factor kappa B (NF-κB), antioxidant parameters, adenosine triphosphate (ATP), adenosine monophosphate (AMP), norepinephrine (NE), dopamine (DA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) cAMP response element-binding protein (CREB) expression and B-cell lymphoma 2 (Bcl-2) expression were measured. The brain’s cognitive functions (Spontaneous locomotor activity, Rotarod performance test, Object recognition test) were assessed. B-Car prevented alteration of the brain’s cognitive function in a dose-dependent manner. The histopathological outcomes supported these biochemical evidences. Based on these results, it could be established that B-Car could be assigned to treat the brain’s neurotoxicity consequences of HE via downregualtion of MAPK/NF-κB signaling pathways.

Keywords: beta-carotene, liver injury, MAPK, NF-κB, rat, thioacetamide

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Authors: Morgane Chatard, Clémentine Puech, Nathalie Perek, Frédéric Roche

Abstract:

Several neurological disorders are linked to repeated hypoxia. The impact of such repeated hypoxic stress, on endothelial cells function of the blood-brain barrier (BBB) is little studied in the literature. Indeed, the study of hypoxic stress in cellular pathways is complex using hypoxia exposure because HIF 1α (factor induced by hypoxia) has a short half life. Our study presents an innovative induction method of repeated hypoxic stress, more reproducible, which allows us to study its impacts on an in vitro contact co-culture BBB model. Repeated hypoxic stress was induced by hydralazine (a mimetic agent of hypoxia pathway) during two hours and repeated during 24 hours. Then, BBB integrity was assessed by permeability measurements (transendothelial electrical resistance and membrane permeability), tight junction protein expressions (cell-ELISA and confocal microscopy) and by studying expression and activity of efflux transporters. First, this study showed that repeated hypoxic stress leads to a BBB’s dysfunction illustrated by a significant increase in permeability. This loss of membrane integrity was linked to a significant decrease of tight junctions’ protein expressions, facilitating a possible transfer of potential cytotoxic compounds in the brain. Secondly, we demonstrated that brain microvascular endothelial cells had set-up defence mechanism. These endothelial cells significantly increased the activity of their efflux transporters which was associated with a significant increase in their expression. In conclusion, repeated hypoxic stress lead to a loss of BBB integrity with a decrease of tight junction proteins. In contrast, endothelial cells increased the expression of their efflux transporters to fight against cytotoxic compounds brain crossing. Unfortunately, enhanced efflux activity could also lead to reducing pharmacological drugs delivering to the brain in such hypoxic conditions.

Keywords: BBB model, efflux transporters, repeated hypoxic stress, tigh junction proteins

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Authors: Hiroyuki Aoki

Abstract:

Molecular imaging has attracted much attention to visualize a tumor site in a living body on the basis of biological functions. A fluorescence in vivo imaging technique has been widely employed as a useful modality for small animals in pre-clinical researches. However, it is difficult to observe a site deep inside a body because of a short penetration depth of light. A photo-acoustic effect is a generation of a sound wave following light absorption. Because the sound wave is less susceptible to the absorption of tissues, an in vivo imaging method based on the photoacoustic effect can observe deep inside a living body. The current study developed an in vivo imaging agent for a photoacoustic imaging method. Nano-particles of poly(lactic acid) including indocyanine dye were developed as bio-compatible imaging agent with strong light absorption. A tumor site inside a mouse body was successfully observed in a photo-acoustic image. A photo-acoustic imaging with polymer nano-particle agent would be a powerful method to visualize a tumor.

Keywords: nano-particle, photo-acoustic effect, polymer, dye, in vivo imaging

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Authors: Yujie Yuan, Yiyang Fan, Hong Fan

Abstract:

Objective: The RNA methylation recognition protein Aly/REF export factor (ALYREF) is considered one type of “reader” protein acting as a recognition protein of m5C, has been reported involved in several biological progresses including cancer initiation and progression. 5-methylcytosine (m5C) is a conserved and prevalent RNA modification in all species, as accumulating evidence suggests its role in the promotion of tumorigenesis. It has been claimed that ALYREF mediates nuclear export of mRNA with m5C modification and regulates biological effects of cancer cells. However, the systematical regulatory pathways of ALYREF in cancer tissues have not been clarified, yet. Methods: The expression level of ALYREF in pan-cancer and their normal tissues was compared through the data acquired from The Cancer Genome Atlas (TCGA). The University of Alabama at Birmingham Cancer data analysis Portal UALCAN was used to analyze the relationship between ALYREF and clinical pathological features. The relationship between the expression level of ALYREF and prognosis of pan-cancer, and the correlation genes of ALYREF were figured out by using Gene Expression Correlation Analysis database GEPIA. Immune related genes were obtained from TISIDB (an integrated repository portal for tumor-immune system interactions). Immune-related research was conducted by using Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) and TIMER. Results: Based on the data acquired from TCGA, ALYREF has an obviously higher-level expression in various types of cancers compared with relevant normal tissues excluding thyroid carcinoma and kidney chromophobe. The immunohistochemical images on The Human Protein Atlas showed that ALYREF can be detected in cytoplasm, membrane, but mainly located in nuclear. In addition, a higher expression level of ALYREF in tumor tissue generates a poor prognosis in majority of cancers. According to the above results, cancers with a higher expression level of ALYREF compared with normal tissues and a significant correlation between ALYREF and prognosis were selected for further analysis. By using TISIDB, we found that portion of ALYREF co-expression genes (such as BIRC5, H2AFZ, CCDC137, TK1, and PPM1G) with high Pearson correlation coefficient (PCC) were involved in anti-tumor immunity or affect resistance or sensitivity to T cell-mediated killing. Furthermore, based on the results acquired from GEPIA, there was significant correlation between ALYREF and PD-L1. It was exposed that there is a negative correlation between the expression level of ALYREF and ESTIMATE score. Conclusion: The present study indicated that ALYREF plays a vital and universal role in cancer initiation and progression of pan-cancer through regulating mitotic progression, DNA synthesis and metabolic process, and RNA processing. The correlation between ALYREF and PD-L1 implied ALYREF may affect the therapeutic effect of immunotherapy of tumor. More evidence revealed that ALYREF may play an important role in tumor immunomodulation. The correlation between ALYREF and immune cell infiltration level indicated that ALYREF can be a potential therapeutic target. Exploring the regulatory mechanism of ALYREF in tumor tissues may expose the reason for poor efficacy of immunotherapy and offer more directions of tumor treatment.

Keywords: ALYREF, pan-cancer, immunotherapy, PD-L1

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Authors: Nandini Nalika, Suhel Parvez

Abstract:

Nanotechnology has emerged to play a vital role in developing all through the industrial world with an immense production of nanomaterials including nanoparticles (NPs). Many toxicological studies have confirmed that due to unique small size and physico-chemical properties of NPs (1-100nm), they can be potentially hazardous. Metallic NPs of small size have been shown to induce higher levels of cellular oxidative stress and can easily pass through the Blood Brain Barrier (BBB) and significantly accumulate in brain. With the wide applications of titanium dioxide nanoparticles (TNPs) in day-to-day life in form of cosmetics, paints, sterilisation and so on, there is growing concern regarding the deleterious effects of TNPs on central nervous system and mitochondria appear to be important cellular organelles targeted to the pro-oxidative effects of NPs and an important source that contribute significantly for the production of reactive oxygen species after some toxicity or an injury. The aim of our study was to elucidate the effect of TNPs in anatase form with different concentrations (5-50 µg/ml) following with various oxidative stress markers in isolated brain mitochondria as an in vitro model. Oxidative stress was determined by measuring the different oxidative stress markers like lipid peroxidation as well as the protein carbonyl content which was found to be significantly increased. Reduced glutathione content and major glutathione metabolizing enzymes were also modulated signifying the role of glutathione redox cycle in the pathophysiology of TNPs. The study also includes the mitochondrial enzymes (Complex 1, Complex II, complex IV, Complex V ) and the enzymes showed toxicity in a relatively short time due to the effect of TNPs. The study provide a range of concentration that were toxic to the neuronal cells and data pointing to a general toxicity in brain mitochondria by TNPs, therefore, it is in need to consider the proper utilization of NPs in the environment.

Keywords: mitochondria, nanoparticles, brain, in vitro

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