Encephalopathy is a term for any diffuse disease of brain that alters brain function or structure with very different etiologies and prognoses. There are some reports that steroids have good effects on some encephalopathies with nonvasculitic autoimmune causes. We describe a 63-year-old woman with a 3-month history of progressive gait disturbance, cognitive decline and increasing confusion in whom steroid treatment resulted in dramatic clinical recovery.
14-3-3 Proteins ; Brain ; Female ; Gait ; Humans ; Middle Aged ; Prognosis ; Steroids

This is a report of a patient with Creutzfeldt-Jakob disease. The 67-year-old male first developed partial and secondary generalized tonic-clonic seizures. He was disoriented and could not perform calculations nor recall objects shown to him 5 minutes earlier. Magnetic resonance images revealed hyperintensities of white matter lesions in fluid-attenuated inversion recovery weighted image. We detected protein 14-3-3 in the cerebrospinal fluid.
14-3-3 Proteins ; Aged ; Cerebrospinal Fluid ; Creutzfeldt-Jakob Syndrome* ; Humans ; Magnetic Resonance Imaging ; Male ; Seizures

BACKGROUND: Creutzfeldt-Jakob disease (CJD) shares common clinical features with Hashimoto's encephalopathy (HE). The 14-3-3 protein is a relatively sensitive and specific marker of CJD but is not commonly detected in HE. We report the case of a patient with HE with unusual features including positive 14-3-3 protein in the cerebrospinal fluid (CSF) and an atypical course mimicking that of CJD. CASE REPORT: A 64-year-old male was admitted due to acute-onset cognitive dysfunction. HE was suspected based on increased titers of anti-thyroid microsomal antibody and an excellent response to steroid. However, 14-3-3 protein was detected in the CSF and a recurrent attack with progressive cognitive decline, pyramidal symptoms and myoclonus mimicking CJD occurred. Cognitive dysfunction showed progressive worsening and the response to steroid treatment was decreased. CONCLUSIONS: 14-3-3 protein could be considered a general marker of neuronal destruction and not specific to CJD. The clinical manifestations of HE are variable and its diagnosis is difficult due to the lack of a specific phenotype and reliable diagnostic criteria. We recommend that patients with clinical features of CJD and antithyroid antibodies should be considered for empirical steroid treatment for HE, despite a positive result for 14-3-3 protein.
14-3-3 Proteins* ; Antibodies ; Cerebrospinal Fluid* ; Creutzfeldt-Jakob Syndrome* ; Diagnosis ; Humans ; Male ; Middle Aged ; Myoclonus ; Neurons ; Phenotype

OBJECTIVE: Purpose of our study was to examine the expression level of 14-3-3 proteins and Bcl-2 family and to estimate the interaction between 14-3-3 proteins and Bcl-2 family in normal and preeclamptic placenta. METHODS: Placental tissues were sampled from preeclampsia with caesarean delivery (n=5) and normal pregnant women with caesarean delivery (n=5). Western blot and immunoprecipitation related Western blotting were performed on all placental samples. Unpaired Student t-test was used to determine the statistical significance. RESULTS: Western blot analysis revealed that the expression of Bax and 14-3-3 zeta was significantly greater in the preeclamptic placenta than in the normal placenta. Immunoprecipitation related Western blotting revealed that the interaction between 14-3-3 zeta and Bax was significantly less in the preeclamptic placenta than in the normal placenta. CONCLUSION: Increased expression of Bax and reduced interaction (between) 14-3-3 zeta and Bax in preeclamptic placenta might influence pathogenesis or sequelae of preeclampsia. Further study is needed to identify the trigger that induces dissociation of Bax from 14-3-3 proteins.
14-3-3 Proteins* ; bcl-2-Associated X Protein ; Blotting, Western ; Female ; Humans ; Immunoprecipitation ; Placenta* ; Pre-Eclampsia* ; Pregnant Women

BACKGROUND: The 14-3-3 sigma (sigma) protein has a negative regulatory role in the cell cycle progression of the. Down-regulation or overexpression of the 14-3-3 sigma protein has been reported in various human cancers. METHODS: Immunohistochemistry for the 14-3-3 sigma protein was performed in non-neoplastic bile duct cells, intraductal papillary neoplasms of the liver (IPNL), mass-forming intrahepatic cholangiocarcinomas (ICC) and non-papillary extrahepatic cholangiocarcinomas (ECC). We investigated the methylation status of the 14-3-3 sigma gene in 45 cases of these 3 tumor groups. RESULTS: The non-neoplastic bile duct cells demonstrated negative or weakly positive cytoplasmic immunoreactivity for the 14-3-3 sigma protein and no methylation of the 14-3-3 sigma gene. Overexpression as well as negative immunoreactivity associated with hypermethylation of the 14-3-3 sigma protein was observed in 16 (69.6%) of 23 cases of IPNL, in 21 (63.6%) of 33 cases of mass-forming ICC and in 27 (71.1%) of 38 cases of non-papillary ECC. Negative immunoreactivity was increased in the invasive IPNL (4/6, 66.7%), as well as in the poorly differentiated cases of mass-forming ICC (8/12, 66.7%) and the non-papillary ECC (5/8, 62.5%). CONCLUSIONS: The similar rates for the abnormal expression of the 14-3-3 sigma protein among the three groups of biliary neoplasms indicate its general association with biliary carcinogenesis. Furthermore, the loss of the 14-3-3 sigma protein may be involved in the tumor progression and differentiation in the biliary carcinogenesis.
14-3-3 Proteins ; Bile Ducts ; Biliary Tract Neoplasms ; Carcinogenesis ; Cell Cycle ; Cholangiocarcinoma ; Cytoplasm ; Down-Regulation ; Humans ; Immunohistochemistry ; Liver ; Methylation*

OBJECTIVEOsteosarcoma is the most common type of malignant bone tumor in children and adolescents. The role of E3 ligases in tumorigenesis is currently a focus in tumor research. In the present study, we investigated the role of the E3 ligase tripartite motif 21 (TRIM21) in osteosarcoma cell proliferation.

METHODS3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays were used to assess osteosarcoma cell viability. U2-OS cells stably carrying a recombinant lentivirus expressing tetracycline-regulated TRIM21 were screened. Co-immunoprecipitation was coupled with LCMS/MS analysis to identify novel interacting partners of TRIM21. Co-immunoprecipitation and bimolecular fluorescence complementation (BIFC) were performed to validate the interactions between TRIM21 and its novel partner YWHAZ. A TRIM21-ΔRING construct was generated to test the effects of TRIM21 ligase activity on YWHAZ.

RESULTSTRIM21 positively regulated osteosarcoma cell proliferation. Overexpression of TRIM21 enhanced osteosarcoma cell tolerance toward various stresses. YWHAZ protein was identified as a novel interacting partner of TRIM21 and its expression levels were negatively regulated by TRIM21. The RING domain of TRIM21 was required for TRIM21 negative regulation of YWHAZ expression. However, overexpression of YWHAZ did not affect positive regulation of osteosarcoma cell proliferation by TRIM21.

CONCLUSIONOur results further clarify the molecular mechanisms underlying the pathogenesis of osteosarcoma.

14-3-3 Proteins ; genetics ; metabolism ; Cell Proliferation ; genetics ; Humans ; Osteosarcoma ; genetics ; Ribonucleoproteins ; genetics ; metabolism ; Tumor Cells, Cultured

To investigate changes of 14-3-3beta from apoptosis induced by PrP106-126 polypeptide, HeLa cell was incubated with PrP106-126 for 4h or 8h. Nucleus changes and the expression of PARP were detected differently by Hoechst staining and Western blotting. Expressing of protein and mRNA from 14-3-3beta was determined by Western blotting and Real-time PCR. The results show that typical nucleus pyknosis and chip of apoptosis and degradation of PARP were induced by PrP106-126 peptide in HeLa cells. Degradation of 14-3-3beta appeared in apoptosis groups induced by PrP106-126 peptide. However, 14-3-3beta mRNA did not display any changes in apoptosis groups. This study indicated that degradation of antiapoptosis protein 143-3beta induced by PrP106-126 peptide may be one of pathogenesis mechanism of prion disease.
14-3-3 Proteins ; metabolism ; Apoptosis ; drug effects ; HeLa Cells ; Humans ; Peptide Fragments ; pharmacology ; Prions ; pharmacology ; Proteolysis ; drug effects

The 14-3-3 proteins comprise a family of highly conserved acidic protein with subunit molecular mass 28-33kD and are widely found in different eukaryotic cells. 14-3-3 proteins were the first polypeptides shown to have phosphoserine/threonine (pSer/Thr) binding properties which firmly established its importance in cell signaling. 14-3-3 proteins tend to form dimeric proteins to modulate protein-protein interactions. 14-3-3 proteins have been shown to contribute to the regulation of such crucial cellular processes as metabolism, signal transduction, cell cycle control, cell growth and differentiation, apotosis, protein trafficking, transcription, stress responses and malignant transformation. Many reports link 14-3-3 to disorders, particularly the neurological disorders and cancer. The 14-3-3 test has been used for the diagnosis of prion diseases. 14-3-3 could be exploited for therapeutic purposes. In this review, we discuss the structure, function of 14-3-3 protein and the related research progress in therapeutic applications.
14-3-3 Proteins ; chemistry ; genetics ; physiology ; therapeutic use ; Humans ; Neoplasms ; diagnosis ; therapy ; Nervous System Diseases ; diagnosis ; therapy

OBJECTIVE: To investigate the changes of GATA-1 protein expression during erythroid differentiation of K562 cells under hypoxia and how GATA-1 can regulate erythroid differentiation by up-regulating the expression of miR-451a and inhibiting the expression of 14-3-3ζ. METHODS: K562 cells were divided into 2 groups: the normoxia group and the hypoxia group, after the induction of hemin for 96 h, the positive cells rate of the benzidine staining, the mRNA expression of γ-globin and the expression of CD235a were detected, and the success of the model was verified. The changes of GATA-1 and miR-451a expression in the above-mentioned 2 groups, the changes of miR-451a expression after over-expressed GATA-1 were detected by Western blot and qRT-PCR. The cells in normoxic group and hypoxia group were divided into negative control group (NC group) and miR-451a over-expression group respectively, and the degree of erythroid differentiation in the four groups was judged according to the corresponding erythroid differentiation indexes, and the expression of 14-3-3ζ was detected by Western blot after over-expressed miR-451a. RESULTS: The positive cell rate of benzidine staining, mRNA expression of γ-globin and the expression of CD235a after 96 h induction by K562 cells under hypoxia were significantly higher than 0 h, suggesting that the erythroid differentiation model of K562 cells under hypoxia was replicated successfully. The expression levels of GATA-1 protein and miR-451a in the hypoxic group were significantly higher than that in the normoxic group (P<0.05). The expression level of miR-451a in hypoxia group was significantly higher than that in NC group after overexpressed GATA-1 (P<0.05). After over-expressed of miR-451a under hypoxia, the positive cell rate of benzidine staining, the mRNA expression level of γ-globin and the expression of CD235a were significantly higher than those in NC group (P<0.05). The expression level of 14-3-3ζ protein in miR-451a over-expressed group was lower than that in NC group under hypoxia (P<0.05). CONCLUSION Hypoxia can significantly increase the expression of GATA-1 protein, and the increase of GATA-1 expression can up-regulate the expression of miR-451a, thereby inhibiting the expression of 14-3-3ζ protein, which hinders the cell proliferation in erythroid differentiation model of K562 cells and plays an important role in promoting erythroid differentiation.
14-3-3 Proteins ; Cell Differentiation ; Erythroid Cells/metabolism* ; GATA1 Transcription Factor/metabolism* ; Humans ; Hypoxia ; K562 Cells ; MicroRNAs/genetics*

BACKGROUND AND PURPOSE: The level of 14-3-3 protein in the cerebrospinal fluid (CSF) is increased in Creutzfeldt-Jakob disease (CJD) patients, which has led to it being used as a clinical biomarker for the ante-mortem diagnosis of human prion diseases. However, the specificity of the 14-3-3 protein is less reliable for CJD diagnosis. Newly developed assays including real-time quaking-induced conversion (RT-QuIC) have made it possible to detect the PrPSc-like abnormal prion isoform with a high sensitivity in animal and human specimens that might contain a minute amount of PrP(Sc) due to in vitro prion replication. METHODS: This study applied a highly sensitive RT-QuIC assay using recombinant human PrP to detect PrP(Sc) in the CSF of 81 patients with sporadic CJD (sCJD) in Korea. RESULTS: RT-QuIC analysis of the CSF samples based on the expression levels of 14-3-3 and total tau proteins revealed positivity in 62 of 81 sCJD patients (sensitivity of 76.5%) but no positive results in the 100 non-CJD patients. CONCLUSIONS: The sensitivity of the RT-QuIC in this study was similar to that in some previous reports, and the specificity of RT-QuIC was higher than that of 14-3-3 in CSF, suggesting that RT-QuIC analysis can complement the weakness of the specificity of 14-3-3 for the diagnosis of sCJD. These results indicate that RT-QuIC might be very useful for the rapid and specific diagnosis of sCJD and provide a practical novel method for the ante-mortem diagnosis of human prion diseases.
14-3-3 Proteins ; Animals ; Cerebrospinal Fluid ; Complement System Proteins ; Creutzfeldt-Jakob Syndrome* ; Diagnosis* ; Humans ; Korea* ; Prion Diseases ; Sensitivity and Specificity ; tau Proteins