Abnormal trial-to-trial variability in P300 time-varying directed eeg network of schizophrenia.

Cognitive disturbance in identifying, processing, and responding to salient or novel stimuli are typical attributes of schizophrenia (SCH), and P300 has been proven to serve as a reliable psychosis endophenotype. The instability of neural processing across trials, i.e., trial-to-trial variability (TTV), is getting increasing attention in uncovering how the SCH "noisy" brain organizes during cognition processes. Nevertheless, the TTV in the brain network remains unrevealed, notably how it varies in different task stages. In this study, resorting to the time-varying directed electroencephalogram (EEG) network, we investigated the time-resolved TTV of the functional organizations subserving the evoking of P300. Results revealed anomalous TTV in time-varying networks across the delta, theta, alpha, beta1, and beta2 bands of SCH. The TTV of cross-band time-varying network properties can efficiently recognize SCH (accuracy: 83.39%, sensitivity: 89.22%, and specificity: 74.55%) and evaluate the psychiatric symptoms (i.e., Hamilton's depression scale-24, r = 0.430, p = 0.022, RMSE = 4.891; Hamilton's anxiety scale-14, r = 0.377, p = 0.048, RMSE = 4.575). Our study brings new insights into probing the time-resolved functional organization of the brain, and TTV in time-varying networks may provide a powerful tool for mining the substrates accounting for SCH and diagnostic evaluation of SCH.

Genome-Wide Association Study Identifies IFIH1 and HLA-DQB1*05:02 Loci Associated With Anti-NMDAR Encephalitis.

BACKGROUND AND OBJECTIVES: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a rare autoimmune neurologic disorder, the genetic etiology of which remains poorly understood. Our study aims to investigate the genetic basis of this disease in the Chinese Han population. METHODS: We performed a genome-wide association study and fine-mapping study within the major histocompatibility complex (MHC) region of 413 Chinese patients with anti-NMDAR encephalitis recruited from 6 large tertiary hospitals and 7,127 healthy controls. RESULTS: Our genome-wide association analysis identified a strong association at the IFIH1 locus on chromosome 2q24.2 (rs3747517, p = 1.06 × 10-8, OR = 1.55, 95% CI, 1.34-1.80), outside of the human leukocyte antigen (HLA) region. Furthermore, through a fine-mapping study of the MHC region, we discovered associations for 3 specific HLA class I and II alleles. Notably, HLA-DQB1*05:02 (p = 1.43 × 10-12; OR, 2.10; 95% CI 1.70-2.59) demonstrates the strongest association among classical HLA alleles, closely followed by HLA-A*11:01 (p = 4.36 × 10-7; OR, 1.52; 95% CI 1.29-1.79) and HLA-A*02:07 (p = 1.28 × 10-8; OR, 1.87; 95% CI 1.50-2.31). In addition, we uncovered 2 main HLA amino acid variation associated with anti-NMDAR encephalitis including HLA-DQß1-126H (p = 1.43 × 10-12; OR, 2.10; 95% CI 1.70-2.59), exhibiting a predisposing effect, and HLA-B-97R (p = 3.40 × 10-8; OR, 0.63; 95% CI 0.53-0.74), conferring a protective effect. Computational docking analysis suggested a close relationship between the NR1 subunit of NMDAR and DQB1*05:02. DISCUSSION: Our findings indicate that genetic variation in IFIH1, involved in the type I interferon signaling pathway and innate immunity, along with variations in the HLA class I and class II genes, has substantial implications for the susceptibility to anti-NMDAR encephalitis in the Chinese Han population.

A hybrid graph network model for ASD diagnosis based on resting-state EEG signals.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder and early diagnosis is crucial for effective treatment. Stable and effective biomarkers are essential for understanding the underlying causes of the disorder and improving diagnostic accuracy. Electroencephalography (EEG) signals have proven to be reliable biomarkers for diagnosing ASD. Extracting stable connectivity patterns from EEG signals helps ensure robustness in ASD diagnostic systems. In this study, we propose a hybrid graph convolutional network framework called Rest-HGCN, which utilizes resting-state EEG signals to capture differential patterns of brain connectivity between normal children and ASD patients using graph learning strategies. The Rest-HGCN combines brain network analysis techniques and data-driven strategies to extract discriminative graph features from resting-state EEG signals. By automatically extracting differential graph patterns from these signals, the Rest-HGCN achieves reliable ASD diagnosis. To evaluate the performance of Rest-HGCN, we conducted ASD diagnosis experiments using k-fold cross-validation on the public ABC-CT resting EEG dataset. The proposed Rest-HGCN model achieved accuracies of 87.12 % and 85.32 % in single-subject and cross-experiment analyses, respectively. The results suggest that Rest-HGCN can effectively capture discriminant graph patterns from resting EEG signals and achieve robust ASD diagnosis. This may provide an effective and convenient tool for clinical ASD diagnosis.

The long-term effect of modulated acoustic stimulation on alteration in EEG brain network of chronic tinnitus patients: An exploratory study.

Acoustic stimulation is one of the most influential techniques for distressing tinnitus, while how it functions to reverse neural changes associated with tinnitus remains undisclosed. In this study, our objective is to investigate alterations in brain networks to shed light on the enigma of acoustic intervention for tinnitus. We designed a 75-day long-term acoustic intervention experiment, during which chronic tinnitus patients received daily modulated acoustic stimulation with each session lasting 15 days. Every 15 days, professional tinnitus assessments were conducted, collecting both electroencephalogram (EEG) and tinnitus handicap inventory (THI) data from the patients. Thereafter, we investigated the changes in EEG network organizations during continuous acoustic stimulation and their progressive evolution throughout long-term therapy, alongside exploring the associations between the evolving changes of the network alterations and THI. Our current study findings reveal reorganization in alpha/beta long-range frontal-parietal-occipital connections as well as local frontal and parietal-occipital regions induced by acoustic stimulation. Furthermore, we observed a decrease in modulation effects as therapy sessions progressed. These alterations in brain networks reflect the reversal of tinnitus-related neural activities, particularly distress and perception; thus contributing to tinnitus rehabilitation through long-term modulation effects. This study provides unique insights into how long-term acoustic intervention affects the network organizations of tinnitus patients and deepens our understanding of the pathophysiological mechanisms underlying tinnitus rehabilitation.

Resting-state network predicts the decision-making behaviors of the proposer during the ultimatum game.

Objective. The decision-making behavior of the proposer is a key factor in achieving effective and equitable maintenance of social resources, particularly in economic interactions, and thus understanding the neurocognitive basis of the proposer's decision-making is a crucial issue. Yet the neural substrate of the proposer's decision behavior, especially from the resting-state network perspective, remains unclear.Approach. In this study, we investigated the relationship between the resting-state network and decision proposals and further established a multivariable model to predict the proposers' unfair offer rates in the ultimatum game.Main results.The results indicated the unfair offer rates of proposers are significantly related to the resting-state frontal-occipital and frontal-parietal connectivity in the delta band, as well as the network properties. And compared to the conservative decision group (low unfair offer rate), the risk decision group (high unfair offer rate) exhibited stronger resting-state long-range linkages. Finally, the established multivariable model did accurately predict the unfair offer rates of the proposers, along with a correlation coefficient of 0.466 between the actual and predicted behaviors.Significance. Together, these findings demonstrated that related resting-state frontal-occipital and frontal-parietal connectivity may serve as a dispositional indicator of the risky behaviors for the proposers and subsequently predict a highly complex decision-making behavior, which contributed to the development of artificial intelligence decision-making system with biological characteristics as well.

Role of hypoxia-inducible factor in postoperative delirium of aged patients: A review.

Postoperative delirium is common, especially in older patients. Delirium is associated with prolonged hospitalization, an increased risk of postoperative complications, and significant mortality. The mechanism of postoperative delirium is not yet clear. Cerebral desaturation occurred during the maintenance period of general anesthesia and was one of the independent risk factors for postoperative delirium, especially in the elderly. Hypoxia stimulates the expression of hypoxia-inducible factor-1 (HIF-1), which controls the hypoxic response. HIF-1 may have a protective role in regulating neuron apoptosis in neonatal hypoxia-ischemia brain damage and may promote the repair and rebuilding process in the brain that was damaged by hypoxia and ischemia. HIF-1 has a neuroprotective effect during cerebral hypoxia and controls the hypoxic response by regulating multiple pathways, such as glucose metabolism, angiogenesis, erythropoiesis, and cell survival. On the other hand, anesthetics have been reported to inhibit HIF activity in older patients. So, we speculate that HIF plays an important role in the pathophysiology of postoperative delirium in the elderly. The activity of HIF is reduced by anesthetics, leading to the inhibition of brain protection in a hypoxic state. This review summarizes the possible mechanism of HIF participating in postoperative delirium in elderly patients and provides ideas for finding targets to prevent or treat postoperative delirium in elderly patients.

Disease-specific resting-state EEG network variations in schizophrenia revealed by the contrastive machine learning.

Given a multitude of genetic and environmental factors, when investigating the variability in schizophrenia (SCZ) and the first-degree relatives (R-SCZ), latent disease-specific variation is usually hidden. To reliably investigate the mechanism underlying the brain deficits from the aspect of functional networks, we newly iterated a framework of contrastive variational autoencoders (cVAEs) applied in the contrasts among three groups, to disentangle the latent resting-state network patterns specified for the SCZ and R-SCZ. We demonstrated that the comparison in reconstructed resting-state networks among SCZ, R-SCZ, and healthy controls (HC) revealed network distortions of the inner-frontal hypoconnectivity and frontal-occipital hyperconnectivity, while the original ones illustrated no differences. And only the classification by adopting the reconstructed network metrics achieved satisfying performances, as the highest accuracy of 96.80% ± 2.87%, along with the precision of 95.05% ± 4.28%, recall of 98.18% ± 3.83%, and F1-score of 96.51% ± 2.83%, was obtained. These findings consistently verified the validity of the newly proposed framework for the contrasts among the three groups and provided related resting-state network evidence for illustrating the pathological mechanism underlying the brain deficits in SCZ, as well as facilitating the diagnosis of SCZ.

Dietary patterns, skeletal muscle mass loss, and cardiovascular risk among elderly men: A preliminary cross-sectional study in Sichuan province.

The present study investigated the correlation between dietary patterns (DPs) with skeletal muscle mass (SMM) and cardiovascular risks in Sichuan males aged ≥65-years-old. Three major DPs were extracted by principal component analysis: animal-based and processed food, traditional food, and ovo-lacto vegetarian food, which accounted for 14.83%, 14.36%, and 11.86% of the variance, respectively. Adjusted logistic regression analysis showed that animal-based and processed food DP was positively associated with overweight/obesity(OR: 3.25, 95% CI: 1.94-5.46) and dyslipidemia(OR: 3.53, 95% CI: 2.00-6.22). Traditional DP was negatively associated with overweight/obesity(OR: 0.51, 95% CI: 0.36-0.72), dyslipidemia(OR: 0.50, 95% CI: 0.35-0.75), and high blood pressure(OR: 0.54, 95% CI: 0.38-0.77), but positively associated with decreased SMM (OR: 2.21, 95% CI: 1.36-3.16). Ovo-lacto vegetarian DP was negatively associated with dyslipidemia (OR: 0.56, 95% CI: 0.39-0.81) and hyperuricemia (OR: 0.56, 95% CI: 0.39-0.79), but positively associated with decreased SMM (OR: 1.57, 95% CI: 0.74-2.32). How to choose the best DP to control the cardiovascular risks and fight skeletal muscle loss needs further investigation in the future.

Alcohol use among patients with epilepsy in western China. A hospital-based study.

AMIS: Alcohol consumption has multiple negative consequences for people with epilepsy, including precipitation of seizure or status epilepticus, worsening of seizure control, increased adverse effects of anti-seizure medications, increased sudden unexpected death in epilepsy, and premature mortality. The aim of this study was to investigate alcohol use and explore the sociodemographic and clinical factors associated with alcohol use among patients with epilepsy in western China. METHODS: A face-to-face questionnaire on alcohol use was conducted at Sichuan Provincial People's Hospital from December 2020 to June 2021. All adult patients who came to our epilepsy center (inpatient and outpatient) were invited to participate in this study. Logistic regression was used to evaluate the possible risk factors associated with alcohol use within the last 12 months. RESULTS: A total of 425 patients completed this study, 24.2% of patients with epilepsy had used alcohol within the last 12 months, being male and having a history of alcohol use were independently associated factors. Among patients who had used alcohol within the last 12 months, 52.4% complained of worsening of seizure control, heavy alcohol use, and frequent alcohol use were independently associated with worsening of seizure control after alcohol use in patients with epilepsy. CONCLUSION: This study revealed that the rate of alcohol use among patients with epilepsy was high. Male patients with a history of alcohol use were more prone to alcohol use after a diagnosis of epilepsy. Heavy alcohol use and frequent alcohol use were independently associated with worsening of seizure control after alcohol use in patients with epilepsy. Patient education on the destructive effects of alcohol use is needed for patients with epilepsy.

Dietary patterns and metabolic syndrome among urbanized Tibetans: A cross-sectional study.

The prevalence of metabolic syndrome (MetS) and the major dietary patterns among urbanized Tibetans are unclear. The present study aimed to investigate the prevalence of MetS among Jiarong Tibetans in Aba Plateau, identify the major dietary patterns, and evaluate their association with the risk of MetS. In this cross-sectional study on 476 subjects, 18-80-years-old, dietary intakes were evaluated using a simplified food frequency questionnaire (SFFQ). MetS was defined according to the International Diabetes Federation (IDF) guidelines. Principal component analysis was performed to assess the major dietary patterns. Multivariate logistic regression analysis examined the associations between dietary patterns and the risk of MetS. The prevalence of Mets in the population was 37.6%. Herein, three major dietary patterns were extracted: traditional Tibetan, urbanized, and healthy dietary patterns. After adjusting for potential confounders (Model 1: adjusted for sex and age; Model 2: adjusted for sex, age, smoking status, drinking situation, physical activity level and total energy intake), subjects in the highest tertile of the healthy dietary had a lower risk of MetS compared to those from the lowest tertile. Also, no significant statistical association was established between the risk of MetS and the traditional Tibetan and urbanized diet.

18F-FDG PET/CT imaging findings of multiple solitary fibrous tumor: A case report.

RATIONALE: Solitary fibrous tumor(SFT) is a rare and distinct clinical entity. There are few descriptions in the literature regarding the PET manifestations of SFTs. Herein,we report a case of multiple malignant SFT with PET/CT imaging findings and PET/Contrast Enhanced CT image findings. PATIENT CONCERNS: A 30-year-old woman presented with a history of a mass in neck increased gradually over 6 months without jaundice or other symptoms of obstruction.Serum laboratory results and tumor markers (AFP, CEA,CA199,CA724,CA153 and CA125)were normal. The whole body PET/CT scan showed lightly or mildly hypermetabolic and inhomogeneous metabolic which was different from other reports, and it was the first report of 18F-FDG-PET/CT findings of multiple malignant SFTs, which were confirmed by positive immunohistochemical staining for CD2-40, CD99, SMA and negative immunohistochemical staining for S100 and CD34. DIAGNOSES: She was diagnosed with multiple malignant solitary fibrous tumors which was confirmed by pathological results and 18F-FDG-PET/CT findings. INTERVENTIONS: The patient didn't receive any treatment because she was not suitable for surgery and refused any other therapy. OUTCOMES: The patient has been followed up for one year,and she was still alive. LESSONS: SFTs should be detected early and treated early.It was of high value in the diagnosis and differential diagnosis of SFTs by PET/CT imaging findings, which can not only identify the benign and malignant lesions, but also identify the lesion involved range.

Aetiological Features of Elderly Patients with Newly Diagnosed Symptomatic Epilepsy in Western China.

AIMS: Recent epidemiological studies have indicated that the incidence of epilepsy peaks after 60 years old, and epilepsy has become increasingly prevalent in elderly populations. The aim of this study is to identify the aetiologic characteristics of epilepsy in the elderly. METHODS: We retrospectively recruited elderly patients with newly diagnosed epilepsy identified in three epilepsy centres in western China; elderly patients were defined as individuals aged 60 years or older. Demographic characteristics, clinical epilepsy data, and the diagnosis and aetiology of epilepsy were recorded. RESULTS: A total of 760 patients with newly diagnosed epilepsy were enrolled in our study. Of these patients, 25% had experienced one or more episodes of status epilepticus, and 62.4% were confirmed as symptomatic. Among the symptomatic cohort, stroke and traumatic brain injury (TBI) were the two most common causes of epilepsy, followed by cerebral tumour, dementia, hippocampal sclerosis (HS), and central nervous system (CNS) infection. When analysed by residence and age, ischaemic stroke was the most common cause of epilepsy in urban patients, whereas traumatic brain injury was the leading cause of epilepsy in rural patients. CONCLUSION: More than three-fifths of newly diagnosed epilepsy cases in elderly patients were confirmed as symptomatic, and stroke and traumatic brain injury were the primary aetiologies in elderly epileptic patients.

Neuroprotective effect of lurasidone via antagonist activities on histamine in a rat model of cranial nerve involvement.

Cranial nerve involvement frequently involves neuron damage and often leads to psychiatric disorder caused by multiple inducements. Lurasidone is a novel antipsychotic agent approved for the treatment of cranial nerve involvement and a number of mental health conditions in several countries. In the present study, the neuroprotective effect of lurasidone by antagonist activities on histamine was investigated in a rat model of cranial nerve involvement. The antagonist activities of lurasidone on serotonin 5­HT7, serotonin 5­HT2A, serotonin 5­HT1A and serotonin 5­HT6 were analyzed, and the preclinical therapeutic effects of lurasidone were examined in a rat model of cranial nerve involvement. The safety, maximum tolerated dose (MTD) and preliminary antitumor activity of lurasidone were also assessed in the cranial nerve involvement model. The therapeutic dose of lurasidone was 0.32 mg once daily, administered continuously in 14­day cycles. The results of the present study found that the preclinical prescriptions induced positive behavioral responses following treatment with lurasidone. The MTD was identified as a once daily administration of 0.32 mg lurasidone. Long­term treatment with lurasidone for cranial nerve involvement was shown to improve the therapeutic effects and reduce anxiety in the experimental rats. In addition, treatment with lurasidone did not affect body weight. The expression of the language competence protein, Forkhead­BOX P2, was increased, and the levels of neuroprotective SxIP motif and microtubule end­binding protein were increased in the hippocampal cells of rats with cranial nerve involvement treated with lurasidone. Lurasidone therapy reinforced memory capability and decreased anxiety. Taken together, lurasidone treatment appeared to protect against language disturbances associated with negative and cognitive impairment in the rat model of cranial nerve involvement, providing a basis for its use in the clinical treatment of patients with cranial nerve involvement.

LncRNA SNHG5 regulates imatinib resistance in chronic myeloid leukemia via acting as a CeRNA against MiR-205-5p.

Imatinib resistance has become a major obstacle for the treatment of chronic myeloid leukemia (CML). The present study aimed to investigate the effects of the long non-coding RNA, SNHG5 on imatinib resistance in CML and explored the underlying mechanisms. The quantitative real-time PCR results showed that SNHG5 and ABCC2 expressions were up-regulated in the isolated peripheral blood cells of the CML patients when compared with healthy controls, and SNHG5 expression levels was positively correlated with ABCC2 in CML patients. In vitro studies showed that the expressions of SNHG5 and ABCC2 were up-regulated in imatinib resistant cells (K562-R) when compared to K562 cells. Bioinformatics analysis showed the interaction between SNHG5 and miR-205-5p, which was further confirmed by luciferase reporter assay and RNA immune-precipitation in K562 cells. Overexpression of SNHG5 suppressed the expression of miR-205-5p and the expression of SNHG5 was negatively correlated with the miR-205-5p expression in CML patients. In addition, ABCC2 was predicted as a downstream target of miR-205-5p, which was further confirmed by the luciferase reporter assay in K562-R cells, and overexpression of miR-205-5p suppressed the expression of ABCC2 in K562-R cells. In vitro functional assay showed that overexpression of SNHG5 in K562 cells increased imatinib resistance and knock-down of SNHG5 reduced the imatinib resistance in K562-R cells. Further experiments showed that SNHG5 promotes imatinib resistance through regulating ABCC2. Taken together, SNHG5 promotes imatinib resistance in CML via acting as a competing endogenous RNA against miR-205-5p.

Development of Small Molecules Targeting the Wnt Signaling Pathway in Cancer Stem Cells for the Treatment of Colorectal Cancer.

Colorectal cancer (CRC) was ranked third in morbidity and mortality in the United States in 2013. Although substantial progress has been made in surgical techniques and postoperative chemotherapy in recent years, the prognosis for colon cancer is still not satisfactory, mainly because of cancer recurrence and metastasis. The latest studies have shown that cancer stem cells (CSCs) play important roles in cancer recurrence and metastasis. Drugs that target CSCs might therefore have great therapeutic potential in prevention of cancer recurrence and metastasis. The wingless-int (Wnt) signaling pathway in CSCs has been suggested to play crucial roles in colorectal carcinogenesis, and has become a popular target for anti-CRC therapy. Dysregulation of the Wnt signaling pathway, mostly by inactivating mutations of the adenomatous polyposis coli tumor suppressor or oncogenic mutations of ß-catenin, has been implicated as a key factor in colorectal tumorigenesis. Abnormal increases of ß-catenin levels represents a common pathway in Wnt signaling activation and is also observed in other human malignancies. These findings highlight the importance of developing small-molecule drugs that target the Wnt pathway. Herein we provide an overview on the current development of small molecules that target the Wnt pathway in colorectal CSCs and discuss future research directions.

Detection of colorectal cancer by DNA methylation biomarker SEPT9: past, present and future.

Colorectal cancer has become the third most common cancer in the world. Early diagnosis and treatment can significantly reduce colorectal cancer mortality. The current routinely used fecal-based screening methods do not provide satisfactory sensitivity. Although colonoscopy provides macroscopic diagnosis, the compliance is low due to its inconvenience and complications. Hence, the development of new screening methods is needed urgently. Peripheral blood SEPT9 gene methylation assay has become a potential option with promising future for early detection and screening of colorectal cancer. It is shown to be convenient, reliable with good compliance by several clinical trials. This article will review the theoretical foundation and development of the assay, focusing on its clinical trials, comparing it with other screening methods and discussing its future applications.

Percutaneous Fine-Needle 5% Ethanol-Cisplatin Intratumoral Injection Combined with Second-Line Chemotherapy Improves On the Standard of Care in Patients with Platinum-Pretreated Stage IV Non-Small Cell Lung Cancer.

BACKGROUND: Efficacy of second-line chemotherapy in platinum-pretreated non-small cell lung cancer (NSCLC) is poor. This study investigated efficacy of computed tomography-guided percutaneous fine-needle 5% ethanol-cisplatin intratumoral injection (CT-PFNECII) combined with second-line chemotherapy in patients with platinum-pretreated stage IV NSCLC. PATIENTS: Between October 2011 and July 2013, 34 eligible patients were randomly assigned to receive either CT-PFNECII combined with second-line chemotherapy (combination group, n = 17) or second-line chemotherapy alone (chemotherapy group, n = 17). The primary end points were the proportions of patients who achieved an overall response rate (ORR) and disease control rate (DCR). Secondary end points were median survival and progression-free survival (PFS). RESULTS: The ORR and DCR in the combination group were significantly higher than in the chemotherapy group (23.53% vs 11.76% for ORR, P < .01; and 58.82% vs 35.29% for DCR, P < .01). Compared with patients in the chemotherapy group, patients in the combination group had significantly longer PFS (5.4 months vs 3.0 months, P < .01) and median survival (9.5 months vs 5.3 months, P < .01). CONCLUSIONS: CT-PFNECII combined with second-line chemotherapy provided a higher response rate and improved survival than second-line chemotherapy for patients with platinum-pretreated stage IV NSCLC.

Different imaging findings of inflammatory myofibroblastic tumor of the liver.

Inflammatory myofibroblastic tumor (IMT) in the liver is an uncommon lesion of uncertain pathogenesis. In most cases, symptomatological imaging and clinical studies suggest malignancy. We report a case of liver IMT with imaging findings from positron emission tomography/computed tomography (PET/CT), contrast-enhanced computed tomography (CECT) and contrast-enhanced ultrasonography (CEUS). This report was the first to depict a PET/CT scan of a liver IMT that revealed an inhomogeneous, intense (fluorine 18)-fluoro-2-deoxy-D-glucose uptake. The CECT and CEUS images showed a hepatic artery supplying blood to the mass and necrosis. The characteristic histopathological features and the presence of spindle cells expressing smooth muscle actin, collagen fibers and lymphocytes allowed for the diagnosis of liver IMT. Recognizing such findings will help to achieve a correct diagnosis and may prevent inappropriate treatment.

Cyclosporine A inhibits breast cancer cell growth by downregulating the expression of pyruvate kinase subtype M2.

The high proliferative rate of tumor cells leads to metabolic needs distinct from those of their normal counterparts. An embryonic- and tumor-specific isoform of the enzyme pyruvate kinase M2 (PKM2) is overexpressed in cancer cells to increase the use of glycolytic intermediates for macromolecular biosynthesis and tumor growth. We report that Cyclosporin A (CsA) can regulate the expression and activity of PKM2 in breast cancer cell lines MCF-7, MDA-MB-435 and MDA-MB-231. PKM2 was found to be highly expressed in the three breast cancer cell lines compared to normal primary breast cells. Treatment with CsA inhibited the viability of breast cancer cells in a time- and dose-dependent manner. CsA significantly downregulated the expression of PKM2 in breast cancer cells and decreased adenosine triphosphate (ATP) synthesis, which induced cancer cells to undergo necrosis. Furthermore, the growth suppression effect of CsA was impaired in MCF-7 cells when they were transfected with the PKM2 overexpression plasmid, suggesting that CsA was an effective inhibitor of PKM2-dependent proliferation of breast cancer cells. These results may provide new insights into the mechanism of CsA in cancer therapy.

Scorpion ethanol extract and valproic acid effects on hippocampal glial fibrillary acidic protein expression in a rat model of chronic-kindling epilepsy induced by lithium chloride-pilocarpine.

The present study analyzed the effects of ethanol extracts of scorpion on epilepsy prevention and hippocampal expression of glial fibrillary acidic protein in a lithium chloride-pilocarpine epileptic rat model. Results were subsequently compared with valproic acid. Results showed gradually-increased hippocampal glial fibrillary acidic protein expression following model establishment; glial fibrillary acidic protein mRNA expression was significantly increased at 3 days, reached a peak at 7 days, and then gradually decreased thereafter. Ethanol extracts of scorpion doses of 580 and 1 160 mg/kg, as well as 120 mg/kg valproic acid, led to a decreased number of glial fibrillary acidic protein-positive cells and glial fibrillary acidic protein mRNA expression, as well as decreased seizure grades and frequency of spontaneously recurrent seizures. The effects of 1 160 mg/kg ethanol extracts of scorpion were equal to those of 120 mg/kg valproic acid. These results suggested that the anti-epileptic effect of ethanol extracts of scorpion were associated with decreased hippocampal glial fibrillary acidic protein expression in a rat model of lithium chloride-pilocarpine induced epilepsy.