Abnormal global and local connectivity in patients with anti-N-methyl-D-aspartate receptor encephalitis: A resting-state functional MRI study.

OBJECTIVE: We decided to investigate the changes of global and local connectivity in anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis patients based on eigenvector centrality (EC) and regional homogeneity (ReHo). We sought new biomarkers to identify the patients based on multivariate pattern analysis (MVPA). METHODS: Functional MRI (fMRI) was performed on all participants. EC, ReHo and MVPA were used to analyze the fMRI images. The correlation between the global or local connectivity and neuropsychology tests was detected. RESULTS: The MoCA scores of the patients were lower than those of the healthy controls (HCs), while the HAMD24 and HAMA scores of the patients were higher than those of the HCs. Increased EC values in the right calcarine (CAL.R) and decreased EC values in the right putamen (PUT.R) distinguished these subjects with anti-NMDAR encephalitis from HCs. The higher ReHo values in the left postcentral gyrus (PoCG.L) were detected in the patients. The correlation analysis showed that the EC values in the PUT.R were negatively correlated with HAMD24 and HAMA scores, while the ReHo values in the PoCG.L were negatively correlated with MoCA scores. Better classification performance was reached in the EC-based classifier (AUC = 0.80), while weaker classification performance was achieved in the ReHo-based classifier (AUC = 0.74) or the classifier based on EC and ReHo (AUC = 0.74). The brain areas with large weights were located in the frontal lobe, parietal lobe, cerebellum and basal ganglia. CONCLUSION: Our findings suggest that abnormal global and local connectivity may play an important part in the pathophysiological mechanism of neuropsychiatric symptoms in the anti-NMDAR encephalitis patients. The EC-based classifier may be better than the ReHo-based classifier in identifying anti-NMDAR encephalitis patients.

Longitudinal alterations of cortical structural-functional coupling in temporal lobe epilepsy.

BACKGROUND AND PURPOSE: To investigate the longitudinal alterations of cortical structural-functional coupling (SF coupling) in patients with temporal lobe epilepsy (TLE) over a 2-year follow-up, thereby exploring the neuropathophysiological mechanisms of TLE. METHODS: Twenty-eight TLE patients and 42 age- and gender-matched healthy controls (HCs) were recruited. We used resting-state functional MRI and diffusion-weighted imaging to estimate and compare SF coupling at the multiscale network level (whole-brain, modular, and regional levels). Then, we analyzed the relationships between the spatial patterns of SF coupling, the principal functional connectivity (FC) gradient, and the functional participation coefficient (PC). Finally, we related regional SF coupling changes between baseline and follow-up to the expression of regional TLE-specific genes. RESULTS: Compared with HCs, TLE patients showed higher baseline SF couplings within the whole-brain, limbic, and default-mode modules. SF couplings within visual and dorsal attention modules were increased at follow-up compared to baseline. In all three groups, the spatial patterns of SF coupling aligned with the principal FC gradient and the functional PC. The longitudinal change in regional SF coupling in TLE patients was significantly positively correlated with the expression of the CUX2 gene. CONCLUSIONS: Aberrant SF coupling was revealed in TLE and related to macroscale cortical hierarchies, functional segregation, and TLE-specific gene expression; these data help increase our understanding of the neuropathophysiological mechanisms underlying TLE.

Cerebral gray matter volume changes in patients with anti-N-methyl-D-aspartate receptor encephalitis: A voxel-based morphometry study.

Background: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disease with typical clinical features. Whether and how cerebral gray matter structural damage inherent to the disorder affects cognitive function in patients is still unclear. Therefore, this study aimed to explore the changes in cerebral gray matter volume and whether these alterations contribute to cognitive impairment and mood disorders. Methods: Forty patients with anti-NMDAR encephalitis and forty healthy controls (HCs) matched for gender, age, and education were recruited. All participants underwent attention network tests (ANT), neuropsychological tests and magnetic resonance imaging (MRI). Voxel-based morphological analysis (VBM) and correlation analysis was performed on all participants. Finally, according to the course of disease, patients were divided into two groups: NMDARE_SD (short duration; course ≤ 2 years since diagnosis) and NMDARE_LD (long duration; course >2 years since diagnosis), to evaluate gray matter volume changes that differ as a function of disease course. Results: Compared to HCs, patients with anti-NMDAR encephalitis showed decreased executive control ability and lower MoCA score, while increased anxiety and depression as reflected by HAMA and HAMD24 scores (all P < 0.05). In VBM analysis, patients showed decreased gray matter volume in bilateral thalamus, left medial prefrontal cortex (mPFC_L), left superior temporal gyrus (STG_L), and left rectus gyrus. In the analysis stratified by disease course, the NMDARE_LD group exhibited decreased gray matter volume in the left precuneus and right posterior cerebellar lobe compared to the NMDARE_SD group. Conclusions: Patients with anti-NMDAR encephalitis have cognitive, executive, and emotional dysfunction, and the sites of gray matter atrophy are concentrated in the thalamus, frontal lobe, and temporal lobe. These abnormalities may be involved in the process of cognitive and affective dysfunction.Patients with different courses of anti-NMDAR encephalitis have different brain atrophy sites. These results may help to clarify the contradiction between clinical and imaging manifestations of anti NMDAR encephalitis, which is worthy of further longitudinal studies.

Disruption of Cerebellar-Cerebral Functional Connectivity in Temporal Lobe Epilepsy and the Connection to Language and Cognitive Functions.

Objective: To investigate the changes in the cerebellar-cerebral language network in temporal lobe epilepsy (TLE) patients from the cerebellar perspective, the research analyzes the changes of language and cognitive network in terms of functional connectivity (FC), as well as their efficiency of the reorganization were evaluated basing on relationship between the network metrics and neuropsychological scale scores. Methods: 30 TLE patients and 30 healthy controls were recruited. Brain activity was evaluated by voxel-mirrored homotopic connectivity analysis (VMHC). Two groups were analyzed and compared in terms of language FC using the following methods: Seed-to-Voxel analysis, pairwise correlations [region of interest(ROI)-to-ROI] and graph theory. Correlation analysis was performed between network properties and neuropsychological score. Results: Compared with healthy participants, VMHC values in the Cerebellum Anterior Lobe, Frontal Lobe, Frontal_Sup_R/L, Cingulum_Ant_R/L, and Cingulum_Mid_R/L were decreased in TLE patients. Decreased FC was observed from the Cerebelum_10_R to the left inferior frontal gyrus, from the Cerebelum_6_R to the left Lingual Gyrus, from the Cerebelum_4_5_R to left Lingual Gyrus, left Cuneal Cortex and Precuneous Cortex, from the Cerebelum_3_R to Brain-Stem, and from the Cerebelum_Crus1_L to Cerebelum_6_R in TLE patients. The FC was enhanced between bilateral Cingulum_Mid and angular gyrus and frontoparietal insular cranium, between Frontal_Sup_Med L and left/right superior temporal gyrus (pSTG l/r), while it was decreased between left middle temporal gyrus and pSTG l/r. Compared with controls, the Betweenness Centrality (BC) of the right superior marginal gyrus (SMG), Temporal_Pole_Mid_R and Temporal_Mid_L as well as the Degree Centrality (DC) and Nodal Efficiency (NE) of the right SMG were lower in TLE patients. Further analysis showed that decreased VMHC in bilateral Cerebellum Anterior Lobe was positively correlated with the Boston Naming Test score in TLE patients, but it was negatively correlated with the Verbal Fluency Test score. The NE and DC of SMG_R were both negatively correlated with visual perception score in Montreal Cognitive Assessment. Conclusion: Our results suggest that presence of abnormalities in the static functional connectivity and the language and cognitive network of TLE patients. Cerebellum potentially represents an intervention target for delaying or improving language and cognitive deficits in patients with TLE.

Correlation Between the Functional Connectivity of Basal Forebrain Subregions and Vigilance Dysfunction in Temporal Lobe Epilepsy With and Without Focal to Bilateral Tonic-Clonic Seizure.

Purpose: Previous research has shown that subcortical brain regions are related to vigilance in temporal lobe epilepsy (TLE). However, it is unknown whether alterations in the function and structure of basal forebrain (BF) subregions are associated with vigilance impairment in distinct kinds of TLE. We aimed to investigate changes in the structure and function BF subregions in TLE patients with and without focal to bilateral tonic-clonic seizures (FBTCS) and associated clinical features. Methods: A total of 50 TLE patients (25 without and 25 with FBTCS) and 25 healthy controls (HCs) were enrolled in this study. The structural and functional alterations of BF subregions in TLE were investigated using voxel-based morphometry (VBM) and resting-state functional connectivity (rsFC) analysis. Correlation analyses were utilized to investigate correlations between substantially altered imaging characteristics and clinical data from patients. Results: FBTCS patients had a lower rsFC between Ch1-3 and the bilateral striatum as well as the left cerebellum posterior lobe than non-FBTCS patients. In comparison to non-FBTCS patients, the rsFC between Ch4 and the bilateral amygdala was also lower in FBTCS patients. Compared to HCs, the TLE patients had reduced rsFC between the BF subregions and the cerebellum, striatum, default mode network, frontal lobe, and occipital lobes. In the FBTCS group, the rsFC between the left Ch1-3 and striatum was positive correlated with the vigilance measures. In the non-FBTCS group, the rsFC between the left Ch4 and striatum was significantly negative correlated with the alertness measure. Conclusion: These results extend current understanding of the pathophysiology of impaired vigilance in TLE and imply that the BF subregions may serve as critical nodes for developing and categorizing TLE biomarkers.

Aberrant resting-state interhemispheric functional connectivity in patients with anti-N-methyl-D-aspartate receptor encephalitis.

PURPOSE: Previous studies have discovered different neuroimaging features in anti-NMDAR encephalitis associated with cognitive dysfunction. However, it is unknown whether there is a correlation between abnormal homotopic connectivity and cognitive impairment in anti-NMDAR encephalitis. We aim to explore the homotopic connectivity patterns of patients with anti-NMDAR encephalitis and their associations with clinical characteristics. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) was performed on 29 patients with anti-NMDAR encephalitis and 26 healthy controls (HCs). Voxel-mirrored homotopic connectivity (VMHC) and multivariate pattern analysis (MVPA) were applied to analyze the imaging data. A correlation was also performed between aberrant brain regions and clinical parameters. RESULTS: Compared to HCs, the performance of alertness in the patient group was typically worse (p < 0.05). A significant decrease in VMHC was observed in many regions of the patients in comparison to HCs, including the cerebellar 6, para-hippocampal gyrus, insula, precuneus, and middle frontal gyrus (p < 0.001). The insula and middle frontal gyrus were found to show positive correlations with alertness. The MVPA method achieved a classification accuracy of 74.55% with a sensitivity of 82.76% and a specificity of 65.38% in discriminating patients from HCs. CONCLUSION: Our findings indicate that interhemispheric functional imbalance may play a significant role in the pathophysiology of cognitive dysfunction in anti-NMDAR encephalitis. The MVPA results suggest that abnormal VMHC may play a crucial role in the identification of patients with anti-NMDAR encephalitis from HCs.

Effect of perioperative blood pressure variability on cerebral hyperperfusion syndrome after carotid artery stenting: A retrospective study.

OBJECTIVE: To investigate the effect of perioperative blood pressure variability on cerebral hyperperfusion syndrome after carotid artery stenting. METHODS: A retrospective analysis was conducted of data collected from 418 patients who underwent carotid artery stenting in Guangxi Zhuang Autonomous Region People's Hospital in China. The blood pressure data were collected during operation (after balloon dilation, before stent release, after stent release) and within 3 days after the operation. The blood pressure variability was evaluated by measuring the mean, maximum, minimum, max-min, standard deviation (SD) of systolic blood pressure (SBP) and diastolic blood pressure (DBP). The correlation between blood pressure variability and cerebral hyperperfusion syndrome was analysed. RESULTS: Blood pressure data from 418 patients were analysed. Twenty patients (4.8%) developed cerebral hyperperfusion syndrome. The parameters of blood pressure variability were divided into four groups according to quartile. After adjusting for age, symptomatic carotid stenosis, unilateral carotid stenosis, bilateral carotid stenosis, collateral circulation, diabetes mellitus and chronic kidney disease, multivariate analysis showed that SBPMax, SBPMin, SBPMax-Min, SBPCV, DBPSD, DBPMax, DBPMin, DBPMax-Min and DBPCV were associated with the occurrence of cerebral hyperperfusion syndrome (P < 0.05), respectively. CONCLUSION: This study suggests that blood pressure variability during the perioperative period may increase the risk of cerebral hyperperfusion syndrome.

Disturbance of functional and effective connectivity of the salience network involved in attention deficits in right temporal lobe epilepsy.

The salience network (SN) acts as a switch that generates transient control signals to regulate the executive control network (ECN) and the default mode network (DMN) and has been implicated in cognitive processes. Temporal lobe epilepsy (TLE) is usually accompanied by different types of cognitive deficits, but whether it is associated with dysfunctional connectivity of the SN remains unknown. To address this, thirty-six patients with right TLE (rTLE) and thirty-six healthy controls (HCs) were recruited for the present study. All of the participants were subjected to attention network test (ANT) and resting-state functional resonance imaging (rs-fMRI) scanning. The patient group showed deficits in attention performance. Moreover, the functional connectivity (FC) and effective connectivity (EC) were analyzed based on key SN hubs (the anterior cingulate cortex (ACC) and the bilateral anterior insula (AI)). When compared with those in the HC group, the ACC showed increased FC with the left middle frontal gyrus and the left precentral gyrus, and the right AI showed decreased FC with the right precuneus and the right superior occipital gyrus in the patient group. The EC analysis revealed an increased inflow of information from the left middle temporal gyrus to the ACC and the right AI and an increased outflow of information from the bilateral AI to the left middle frontal gyrus. Furthermore, in the correlation analysis, the abnormal EC from the right AI to the left middle temporal gyrus was positively correlated with the executive control effect. These findings demonstrated aberrant modulation of the SN in rTLE, which was particularly characterized by dysfunctional connectivity between the SN and key brain regions in the DMN and ECN. Elucidation of this effect may further contribute to the comprehensive understanding of the neural mechanisms of the SN in regard to attention deficits in patients with TLE.

Inhibition of CAMK II modulates water permeability by reducing AQP4 expression in astrocytes after oxygen-glucose deprivation.

The predominant form of edema that occurs during the early stage of ischemic stroke is cytotoxic, resulting in neuronal injury during brain ischemia and reperfusion. Intracellular calcium (Ca2+) is elevated following brain ischemia leading to increased cell membrane permeability. Ca2+/calmodulin-dependent protein kinase II (CaMK II), the downstream molecular signal of N-methyl-d-aspartate receptors (NMDARs), is sensitive to elevations in intracellular Ca2+. Aquaporin-4 (AQP4), which is expressed primarily in the brain, is a water-transport protein. However, it is unclear whether CaMK II regulates AQP4 expression to modulate cellular water permeability. We exposed cultured astrocytes to a hypoxic and glucose-free environment to mimic an ischemic environment in vitro. We investigated the effects of oxygen-glucose deprivation (OGD) on astrocytic viability and swelling, as well as CaMK II and AQP4 expression. We also studied the effects of CaMK II inhibition on cell swelling, viability and AQP4 expression. OGD increased astrocytic swelling and expression of CaMK II and AQP4, and it decreased astrocyte viability. Inhibition of CaMK II resulted in reduced astrocyte water permeability and AQP4 expression. We concluded that the upregulation of CaMK II promoted astrocyte swelling by increasing the expression of AQP4 after OGD.

A selective NLRP3 inflammasome inhibitor attenuates behavioral deficits and neuroinflammation in a mouse model of Parkinson's disease.

Nod-like receptor pyrin containing (NLRP)3 inflammasome-mediated neuroinflammation is involved in the pathology of Parkinson's disease (PD), but the roles of other inflammasomes in PD remain unclear. The NLRP3 inhibitor MCC950 exerts neuroprotective effects in several neurological diseases. Using a 1-methyl-4-phenyl-1,2,3,6-tetrahydro pyridine (MPTP)-induced mouse model with or without intraperitoneal MCC950 administration, we assessed whether specifically the NLRP3 inflammasome is activated in the nigrostriatal system and whether MCC950 has therapeutic potential in this PD model. Western blots were used to determine the nigrostriatal expression of inflammasome-specific proteins, including NLRP1, NLRP2, NLRP3, nod-like receptor CARD containing 4 (NLRC4), and absent in melanoma 2 (AIM2). The pole, hanging, and swimming tests were used to assess functional deficits, western blots and immunostainings were used to analyze dopaminergic neuronal degeneration, as well as activation of glial cells and the NLRP3 inflammasome. NLRP3 expression in the nigrostriatal system of MPTP-induced mice was significantly increased compared to control, whereas NLRP1, NLRP2, NLRC4, and AIM2 expression in the nigrostriatal system, as well as NLRP3 expression in the cerebral cortex and hippocampus, were similar in the two groups. Furthermore, MPTP-induced mice exhibited behavioral dysfunctions, dopaminergic neuronal degeneration, and activation of glial cells and the NLRP3 inflammasome. MCC950 treatment of MPTP-induced mice improved behavioral dysfunctions, reduced dopaminergic neuronal degeneration, and inhibited the activation of glial cells and the NLRP3 inflammasome. In conclusion, these findings indicated that NLRP3, not NLRP1, NLRP2, NLRC4, and AIM2, may be the key inflammasome that promotes MPTP-induced pathogenesis. MCC950 protects against MPTP-induced nigrostriatal damage and may be a novel promising therapeutic approach in treating MPTP-induced PD.

Silencing matrix metalloproteinase 9 exerts a protective effect on astrocytes after oxygen-glucose deprivation and is correlated with suppression of aquaporin-4.

Cerebral ischemia, followed by brain edema, can be life-threatening. It has been widely reported that matrix metalloproteinase-9 (MMP-9) and aquaporin-4 (AQP4) have prominent roles in the development of brain edema. However, the exact mechanisms by which MMP-9 and AQP4 influence brain edema are not fully understood. In this study, astrocytes were subjected to oxygen-glucose deprivation (OGD) /reperfusion (OGD/R) injury, an in vitro model of Ischemia/reperfusion (I/R). Cell viability was evaluated through the measurement of LDH release. The expression of MMP-9 and AQP4 also were measured by qPCR and western blot. Subsequently, we knocked out the MMP-9 gene using MMP-9 siRNA. AQP4 and its gene expression, and the LDH release rate were measured using ELISA, Western blotting, and RT-PCR. We also assessed cAMP-dependent protein kinase (PKA), cGMP-dependent protein kinase (PKG), protein kinase C (PKC), and Ca2+/calmodulin-dependent protein kinase II (CaMK II) in MMP-9 knockout astrocytes. All measurements were performed with or without an OGD/R challenge. OGD/reperfusion enhanced LDH release levels, and also increased MMP-9 and AQP4 expression in astrocytes. Silencing the MMP-9 gene decreased LDH release levels, and also was associated with decreased AQP4 expression. The expression of PKC, but not PKA, PKG, or CaMK II, was decreased. This study revealed that OGD/reperfusion could cause cell damage in vitro. MMP-9 silencing protected astrocytes from hypoxic insult, and the protective effect may be enhanced by the downregulation of AQP4 expression. In conclusion, downregulating MMP-9 expression may be useful for the prevention and treatment of brain ischemia.

[Corrigendum] Overexpression of the chimeric plasmin-resistant VEGF165/VEGF183 (132-158) protein in murine breast cancer induces distinct vascular patterning adjacent to tumors and retarded tumor growth.

After the publication of the article, the authors noted that they had made an error regarding certain facts in their manuscript: In the abstract VEGF192 (132-158) should be changed to VEGF183 (132-158) (Page 1, Line 2). In addition, width should be changed to width2 (Page 3, Line 50). The authors regret these errors. [the original article was published in the Molecular Medicine Reports 11: 1483-1489, 2015 DOI: 10.3892/mmr.2014.2866]

Overexpression of VEGF183 promotes murine breast cancer cell proliferation in vitro and induces dilated intratumoral microvessels.

Vascular endothelial growth factor (VEGF) was considered as a critical growth factor for tumor expansion. The roles of VEGF121, VEGF165, and VEGF189 in tumor growth have been intensely investigated; however, involvements of another extracellular matrix (ECM)-binding VEGF isoform, namely VEGF183 (six amino acids shorter than VEGF189 in exon 6a), in physiological or pathological processes are still unclear although the wide tissue distribution. To investigate the role of VEGF183 in carcinogenesis, we generated murine breast cancer cell (EMT-6) clones stably overexpressing VEGF183, VEGF121, VEGF165, and VEGF189 shortened as V183, V121, V165, and V189, respectively. Methylthiazolyldiphenyl-tetrazolium bromide (MTT) results showed that VEGF183, like all other VEGF-overexpressing isoforms except for VEGF121, could enhance the proliferation of mouse breast cancer EMT-6 cells. Immunochemistry results displayed that overexpressing VEGF183 and VEGF189 in EMT-6 cells induced larger proportional dilated microvessels. On the other hand, results from cell wound healing experiments demonstrated that all of the VEGF-overexpressing isoforms could increase the chemotaxis of EMT-6 cells in vitro. In conclusion, our results supported the idea that overexpression of VEGF183 promotes murine breast cancer cell proliferation in vitro and induces dilated intratumoral microvessels, and it plays a dissimilar role in comparison with that of VEGF189.

Overexpression of the chimeric plasmin-resistant VEGF165/VEGF183 (132-158) protein in murine breast cancer induces distinct vascular patterning adjacent to tumors and retarded tumor growth.

A chimeric plasmin­resistant vascular endothelial growth factor (VEGF)165/VEGF183 (132-158) protein, named as VEGF183 (according to the nomenclature of VEGF), designed by a previous study, was demonstrated to have an enhanced affinity for the extracellular matrix (ECM) amongst other bioactivities. However, it is now accepted that mutant VEGFs frequently demonstrate different angiogenic activities and produce different vascular patterning from the parental molecule. The present study hypothesized that VEGF183, due to its enhanced binding affinity to the ECM, would exhibit a different angiogenic activity and produce a different vascular patterning compared to those of VEGF165. Murine breast cancer EMT­6 cells were manipulated to stably overexpress VEGF165 or VEGF183. These cells were then inoculated intradermally into BALB/c mice in order to monitor the formation of vascular patterning in skin proximal to tumors. In vivo angiogenesis experiments revealed that overexpression of VEGF183 in murine breast cancer cells resulted in irregular, disorganized and dense vascular patterning as well as induced a significant inhibition of tumor growth compared with that of VEGF165. In addition, allograft tumor immunochemical assays of VEGF183­overexpressing tumors demonstrated significantly lower vascular densities than those of VEGF165­overexpressing tumors; however, VEGF183 tumors had a significantly enlarged vascular caliber. Conversely, cell wound healing experiments revealed that VEGF183­overexpressing EMT­6 cells had significantly decreased migration rates compared with those of VEGF165­overexpressing EMT­6 cells. In conclusion, the results of the present study supported the hypothesis that the altered ECM affinity of VEGF induced structural alterations to vasculature. In addition, these results provided a novel insight into VEGF design and indirect evidence for the function of exon 8 in VEGF. [Corrected]

Isolation and identification of a new ent-kaurane diterpenoid from the leaves of Isodon japonica.

A new ent-kaurane diterpenoid, 3α, 14ß, 16α-trihydroxy-ent-kaurane (1), together with seven known diterpenoids (2-8), was isolated from the leaves of Isodon japonica. Their structures were elucidated by spectroscopic methods, including 1D and 2D NMR experiments, IR, HR-ESI-MS and X-ray crystallographic analysis.

Abnormal expression of fibrinogen gamma (FGG) and plasma level of fibrinogen in patients with hepatocellular carcinoma.

UNLABELLED: Abnormal expression of genes has been related to progression of hepatocellular carcinoma (HCC). The present study investigated the mRNA expression of fibrinogen gamma (FGG) in HCC and levels of plasma fibrinogen of patients with HCC. MATERIALS AND METHODS: Northern blot and semiquantitative RT-PCR were performed to determine the mRNA transcription of FGG. The plasma fibrinogen was measured quantitatively by the von Clauss method. RESULTS: FGG was significantly up-regulated at the mRNA level in the SMMC-7721 and HepG2 HCC cell lines. FGG mRNA transcript was also up-regulated in HCC tissues when compared to non-cancerous adjacent tissues as control. The laboratory investigation of blood samples from 114 HCC patients showed significantly higher levels of plasma fibrinogen compared to healthy persons as control (3.75+/-1.41 vs. 2.90+/-0.46 g l(-1)) (p<0.01). Moreover, plasma fibrinogen increased progressively with the tumor clinical stage of HCC patients. By multivariate logistic regression analysis, a positive level of plasma fibrinogen was found to have a significant correlation with the presence of tumor thrombosis. CONCLUSION: FGG mRNA was expressed abnormally in HCC and elevated plasma fibrinogen may serve as a useful predictor of clinical progression of HCC patients.

Messenger RNA expression of translationally controlled tumor protein (TCTP) in liver regeneration and cancer.

OBJECTIVE: Translationally controlled tumor protein (TCTP) was recently reported to be involved in tumor reversion. In order to understand TCTP mRNA transcript in proliferative tissue and malignant lesions, the mRNA expression of TCTP was determined in a rat model of liver regeneration and human liver cancer tissues. In addition, the potential role of TCTP on suppression of liver cancer was investigated. MATERIALS AND METHODS: Liver regeneration model was established by a two-thirds partial hepatectomy (PH) in adult, male Sprague-Dawley rat. TCTP mRNA expression was determined by semiquantitative RT-PCR analysis. Antisense mRNA of TCTP was transfected into the SMMC-7721 liver cancer cell line. Biological assay of proliferation and cell cycle were analysed by MTT and flow cytometry, respectively. RESULTS: After PH of rats, the level of TCTP mRNA transcript was upregulated slightly in liver tissue at 1 hour followed by a high expression from 3 to 12 hours, which then decreased dramatically at 24 hours before returning to original level during liver tissue proliferation. TCTP mRNA transcript increased significantly in liver cancer tissues when compared to non-cancerous adjacent tissues as control. The transfection with antisense oligodeoxynucleotides of TCTP led to decreased proliferation of SMMC-7721 cells resulting in cell cycle arrest and pro-apoptosis. CONCLUSION: The results suggested that TCTP mRNA expression might be stage-specific in the proliferation of liver tissue but alter abnormally in cancer lesions. TCTP could be used as a potential target for suppression of liver tumorigenicity.

[Cloning and identification of fibrinogen gamma polypeptide (FGG) gene differentially expressed in human hepatocellular carcinoma].

BACKGROUND & OBJECTIVE: Abnormal expression of genes is related to development and progression of hepatocellular carcinoma (HCC); however, the detailed mechanism is unclear yet because the known genetic information is not sufficient at present. This study was to explore cloning and identification of fibrinogen gamma polypeptide (FGG) gene differentially expressed in human hepatocellular carcinoma. METHODS: The suppression subtractive hybridization was used to obtain subtracted cDNA products of HCC, then the products were cloned by T/A method. The differential expression of gene in HCC was identified by DNA sequencing analysis, Northern blot analysis, rapid amplification of cDNA end (RACE), and reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Firstly, a cDNA fragment of 787 nucleotides was screened from the subtracted cDNA clones, and it was further discovered that the expression of the cDNA fragment was higher significantly in human hepatocellular carcinoma cell strains of SMMC-7721 and HepG2 than in normal hepatocytes by Northern blot analysis. The RACE was carried out and the gene of 1 597 bp containing polyA in 3'end was obtained, which has an entire open reading frame encoding 437 amino acids. Homology analysis showed that this was a gene encoding human FGG. RT-PCR analysis of FGG showed that the amplification of cancerous tissues, especially in metastasis of HCC, was raised as compared to that of adjacent non-cancerous tissues. CONCLUSION: Overexpression of FGG was discovered in SMMC-7721 and HepG2 cells. The up-regulation of FGG may be associated with the pathogenesis of HCC.