Magnetic resonance imaging assessment of substantia nigral iron deposition in Parkinson's disease: a meta-analysis.

OBJECTIVE: The pathogenesis of Parkinson's disease (PD) is associated with abnormal iron accumulation. Magnetic resonance imaging (MRI) studies have shown that patients with Parkinson's disease have an increased amount of iron in their substantia nigra (SN). We have undertaken a meta-analysis of studies using MRI in PD, to explore the potential role of MRI in diagnosing PD using abnormal iron deposition in SN as a candidate biomarker. MATERIALS AND METHODS: Searches of PubMed, Embase, and Medline databases revealed 16 studies that compared PD patients and healthy controls (HC). A sensitivity analysis and subgroup analysis were performed to evaluate the reliability of our results. Estimates were pooled by the fixed-effects model. As an expression of I2, we computed the proportion of variation due to heterogeneity. RESULTS: We included 16 studies with sample sizes of 435 PD and 355 HC in our meta-analysis. Results showed that SN iron deposition was significantly elevated (p<0.00001) in patients with PD compared to HC ones (SMD=0.72, 95% confidence interval 0.57 to 0.87, p<0.00001). CONCLUSIONS: Our findings, based on a homogeneous group-level analysis, suggest that MRI-based SN iron deposition could be used to distinguish PD from HC. For a more rigorous investigation of SN iron deposition in PD, larger cohort studies are needed.

Overexpression of UBE2C correlates with poor prognosis in gastric cancer patients.

OBJECTIVE: The ubiquitin-conjugating enzyme E2C (UBE2C) has been known as a crucial factor upregulated in various tumors. The functions of UBE2C is mainly involved in the pathway protein ubiquitination. This study investigates the expression of UBE2C in gastric cancers and its correlation with overall survival rate. MATERIALS AND METHODS: Real-time PCR (RT-PCR) and Western blotting were performed to determine the expression of UBE2C in gastric cancer samples and adjacent normal tissues. Immunohistochemical staining was used to assess the expression of UBE2C in 216 paraffin-embedded gastric cancer tissues. RESULTS: The mRNA and relevant protein levels of UBE2C in gastric cancer tissues are significantly greater than those in the adjacent normal tissues. Also, the expression of UBE2C is found to correlate with lymphatic metastasis, serosa invasion, TNM (Malignant Tumors) staging and Lauren's classification (p<0.05). The univariate analysis shows that the overexpression of UBE2C associates with poor prognosis (p=0.001). The multivariate analysis demonstrates that expression of UBE2C, lymphatic metastasis, and TNM staging are independent prognostic indicators. CONCLUSIONS: This study shows that overexpression of UBE2C contributes to the development of gastric cancer, and UBE2C has the potential to be exploited as a therapeutic target.

The investigation of genetic and clinical features in Chinese patients with juvenile amyotrophic lateral sclerosis.

Juvenile amyotrophic lateral sclerosis (JALS) occurs at an age of onset below 25 years with a heterogeneous disease onset location, variable progression and survival time. To investigate whether an ALS gene profile could resolve any aspects of clinical symptom heterogeneity, we have used targeted sequencing technology in a cohort of 12 JALS patients of Chinese descent. We detected 5 likely pathogenic mutations, 2 in familial probands and 3 in sporadic patients. One was a known TARDBP mutation (p.G348V) and 4 were FUS frameshift mutations including a known p.Gln519Ilefs*9 mutation and 3 novel mutations, p.Gly515Valfs*14, p.Gly486Profs*30, and p.Arg498Alafs*32. Of the 4 FUS mutations, 2 were able to be confirmed as de novo mutations. The TARDBP mutation carrier showed a classic ALS phenotype. All patients with FUS mutations experienced limb weakness at an early age and developed bulbar symptoms during the disease course. FUS mutations have previously been associated with increased JALS disease progression, however, we found a large range 12 to 84 months in disease survival (mean 58.2 months). Our results justify future screening for variants in FUS as it remains the most frequent genetic determinant of early onset, JALS (found in 30% of our patients).

Risks of undernutrition and malnutrition in hospitalized pediatric patients with spinal cord injury.

STUDY DESIGN: Prospective study. OBJECTIVES: To describe the nutritional risk/status of Chinese children with spinal cord injury (SCI) at admission and determine the relationship between nutritional risk/status and demography/SCI characteristics. SETTING: China Rehabilitation Research Center, Beijing, China. METHODS: Baseline clinical data, appetite level, anthropometric measurements and Screening Tool for the Assessment of Malnutrition in Pediatrics (STAMP) scores were obtained for pediatric SCI patients. The relationships among the demographic/SCI characteristics and STAMP score and z-scores of weight-for-age (WAZ), height-for-age (HAZ) and body mass index-for-age (BAZ) were assessed. The risk of undernutrition was compared with actual nutritional status. RESULTS: Forty-five children including 12 boys and 33 girls were included. The risks of undernutrition using the STAMP tool and malnutrition were 51.1% and 55.6%, respectively. Children with different demographic characteristics had similar nutritional status and risk of malnutrition. The risk of undernutrition was associated with nutritional status, including WAZ (P<0.001), HAZ (P=0.001), BAZ (P<0.001) and appetite level (P<0.001). Compared with nutritional status, STAMP had a sensitivity of 100%, a specificity of 73.3% and an overall agreement of 82.2%. As the duration of SCI increased, the risks of overweight and stunting increased. CONCLUSIONS: Nutritional screening in all pediatric SCI patients should be performed periodically. The decreasing trends in nutritional status and appetite level after SCI require special attention. The STAMP may be an alternative method for assessing nutritional status in Chinese children with SCI.

Mucormycosis or extranodal natural killer/T cell lymphoma, similar symptoms but different diagnosis.

Facial mucormycosis and extranodal natural killer/T cell lymphoma (NK/TCL) are characterized by facial progressive swelling, ulceration and destruction. Patient one was a 58-year-old woman, who had typical clinical-pathological symptoms of tumor. She was hospitalized in order to remove the tumor. But the diagnosis turned out to be primary mucor infection, which was corrected by positive tissue culture and fungal elements in histology. She was also diagnosed with type 2 diabetes mellitus and acute myelocytic leukemia M2a. With the antifungal therapy, her symptoms, signs and general conditions improved. Regrettably, she gave up the treatment, and died three months later for unknown reason. Patient two was a 60-year-old woman, with the complaints of chronic sinusitis, swelling and necrotic lesion in the right temporal area. Although the mycelium was recovered in biopsy tissues from the necrotic lesion, the diagnosis was revised to extranodal NK/TCL by reviewing the histopathological features and immunophenotypic analysis. The patient also voluntarily abandoned treatment, and died at home for unknown reason. The differential diagnosis of facial mucormycosis and extranodal NK/TCL is usually perplexing.

The regulatory effects of autophagy to the CNE2 cells radio-sensitization.

To investigate the effects of autophagy activator and autophagy inhibitor on the CNE2 radiation sensitivity of nasopharyngeal carcinoma cells. RNA interference technology was used to silence the atg5 gene and autophagy inhibition cell model was constructed. Rapamycin and chloroquine were treated respectively on cells with X-ray 5Gy irradiation. Cells' growth status were observed for 8 days and control group was set. The cell viability was detected by MTT assay and colony formation assay, and the cell cycle was analyzed by flow cytometry. Compared with the control group, the survival rate, clone formation rate and the survival rate of the irradiation of the other three groups were significantly lower. (P<0.05) Most cells were detected in the G0/G1 phase in the other three groups except the control group, and cells of the other two periods were less than those in the G0/G1 phase. The autophagy inhibitor or activator and atg5 silencing can be increased by CNE2 radiation therapy, however, the sensitization effect increase of autophagy activator is better than others.

Protective effect of nicotine on the cultured rat basal forebrain neurons damaged by ß-Amyloid (Aß)25-35 protein cytotoxicity.

OBJECTIVE: We sought to investigate the intervention effect of nicotine on ß-amyloid (Aß)25-35 protein cytotoxicity in the rat basal forebrain neurons primary cultures. MATERIALS AND METHODS: For this purpose, freshly isolated rat basal forebrain neurons were cultured for 7 days and then exposed to either Aß(25-35) or the combination of Aß(25-35) and nicotine for 48 hours. The effects of Aß(25-35) and nicotine on neurons morphology, growth status and TrkA expression were evaluated through microscopy, MTT assay, RT-PCR and immunocytochemistry. RESULTS: We found that the exposure of cultured neurons to Aß(25-35) resulted in remarkable morphological changes. The average process number and length as well as the maximum process length of neurons were significantly decreased as compared with those of control. MTT assay showed that Aß(25-35) impaired the growth of neurons. Aß(25-35) also inhibited the expression of TrkA at both mRNA and protein levels. However, the addition of nicotine significantly attenuated these changes, indicating that nicotine could protect the neurons from the cytotoxicity of Aß(25-35). CONCLUSIONS: Nicotine could be useful for the treatment of Alzheimer's disease through its ability to rescue the neurons from Aß(25-35) cytotoxicity and the protective effect involved upregulated expression of TrkA receptors.

Laboratorial characteristics of patients with diarrhoea suffering from egg white allergy

BACKGROUND: Egg allergy is associated with diarrhoeal symptoms. However, the mechanism underlying allergic diarrhoea remains unclear. OBJECTIVE: To determine whether egg white-specific IgE antibodies coexist with egg white-specific IgG antibodies in patients with egg allergy featuring diarrhoeal symptoms, and whether there is any relationship between these two antibody types. METHODS: A total of 89 patients with egg allergy featuring diarrhoeal symptoms (average age, 23.2 years; range, 1-78 years), all of whom tested positive for egg white-specific IgG, were enrolled in this study. The concentration of total IgE, egg white-specific IgE and number of eosinophils in the serum were determined. RESULTS: Among the 89 egg white allergic patients tested, 49 (55.1%) patients showed high reactivity to egg white-specific IgG, 48 (53.9%) patients had elevated serum total IgE levels, and 25 (28.1%) patients had elevated absolute eosinophil numbers. Out of the 89 egg white allergic patients, 25 showed elevated egg white-specific IgE antibody levels. Of the 25 patients who were positive for egg white-specific IgE antibody, 21 presented high sensitive reaction to egg white-specific IgG, three presented moderate sensitive reaction to egg white-specific IgG, and one presented mild sensitive reaction to egg white-specific IgG. A moderate correlation between egg white-specific IgG and egg white-specific IgE, egg white-specific IgG and absolute eosinophil number was found in the egg white allergic patients (r = 0.438, P = 0.000; r = 0.322, P = 0.002). Egg white-specific IgE levels varied in different age groups; the egg white-specific IgE concentration of younger patients (age ≤ 18 years, mean rank 54.29) was significantly higher than that of the adult patients (age > 18 years, mean rank 34.61) (Z = −3.629, P = 0.000). CONCLUSION: Egg white-specific IgE antibody could coexist with egg white-specific IgG antibody in patients suffering from egg white allergy. Aberrant changes in the concentration of egg white-specific IgE antibody were associated with the presence of egg white-specific IgG antibody

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Laboratorial characteristics of patients with diarrhoea suffering from egg white allergy.

BACKGROUND: Egg allergy is associated with diarrhoeal symptoms. However, the mechanism underlying allergic diarrhoea remains unclear. OBJECTIVE: To determine whether egg white-specific IgE antibodies coexist with egg white-specific IgG antibodies in patients with egg allergy featuring diarrhoeal symptoms, and whether there is any relationship between these two antibody types. METHODS: A total of 89 patients with egg allergy featuring diarrhoeal symptoms (average age, 23.2 years; range, 1-78 years), all of whom tested positive for egg white-specific IgG, were enrolled in this study. The concentration of total IgE, egg white-specific IgE and number of eosinophils in the serum were determined. RESULTS: Among the 89 egg white allergic patients tested, 49 (55.1%) patients showed high reactivity to egg white-specific IgG, 48 (53.9%) patients had elevated serum total IgE levels, and 25 (28.1%) patients had elevated absolute eosinophil numbers. Out of the 89 egg white allergic patients, 25 showed elevated egg white-specific IgE antibody levels. Of the 25 patients who were positive for egg white-specific IgE antibody, 21 presented high sensitive reaction to egg white-specific IgG, three presented moderate sensitive reaction to egg white-specific IgG, and one presented mild sensitive reaction to egg white-specific IgG. A moderate correlation between egg white-specific IgG and egg white-specific IgE, egg white-specific IgG and absolute eosinophil number was found in the egg white allergic patients (r=0.438, P=0.000; r=0.322, P=0.002). Egg white-specific IgE levels varied in different age groups; the egg white-specific IgE concentration of younger patients (age≤18 years, mean rank 54.29) was significantly higher than that of the adult patients (age>18 years, mean rank 34.61) (Z=-3.629, P=0.000). CONCLUSION: Egg white-specific IgE antibody could coexist with egg white-specific IgG antibody in patients suffering from egg white allergy. Aberrant changes in the concentration of egg white-specific IgE antibody were associated with the presence of egg white-specific IgG antibody.

Phosphorylation of human La protein at Ser 366 by casein kinase II contributes to hepatitis B virus replication and expression in vitro.

Human La protein (hLa) is a multifunctional RNA-binding protein involved in the regulation of hepatitis B virus (HBV) expression. Casein kinase II (CK2), a protein kinase, is known to activate hLa by phosphorylating Ser(366). Tetrabromobenzimidazole (TBBz) has been shown to be a specific inhibitor of CK2 activity, which suggests that TBBz may be useful for reducing HBV gene expression. The aim of our study was to determine whether inhibition of CK2 by TBBz and decreased phosphorylation of hLa Ser(366) (pLa) would reduce HBV gene expression. pLa and total La expression levels were evaluated by immunohistochemistry in human liver tissues with or without HBV infection. HepG2.2.15 cells (an HBV-expressing cell line) were treated with TBBz, and cell viability and pLa levels were evaluated. Knockdown of hLa and CK2 levels by specific siRNA and mutant hLa Ala(366) were utilized to establish the roles of pLa and CK2 in HBV gene expression. HBV DNA replication and HBsAg and HBeAg levels were analysed in HepG2.2.15 cell supernatants by standard methods. pLa was significantly overexpressed in HBV-infected human liver samples. TBBz decreased the phosphorylation of hLa, which coincided with decreased HBV expression. Mutant hLa Ala(366) had reduced viral expression compared with hLa Ser(366) treatment in hLa siRNA knockdown cells. Knockdown of CK2 also decreased the HBV parameters. hLa plays a key role in the regulation of HBV gene expression in a CK2-dependent mechanism via phosphorylation of hLa at Ser(366).

A systematic analysis of the predicted human La protein targets identified a hepatitis B virus infection signature.

The human La (hLa) protein functions in RNA metabolism and is activated by casein kinase 2 (CK2) phosphorylation. Hepatitis B virus (HBV) can exploit hLa to stabilize its RNA and promote its pathogenesis. To enhance our knowledge of host molecular pathways involved in HBV pathogenesis, a bioinformatic approach was used to generate an expression profile of all predicted target genes of CK2-activated hLa in HBV-infected cells. A computerized literature search was performed to identify English language studies of HBV-, hLa- and CK2-related molecules. The data were pooled and the genes were classified in three functional groups by gene ontology (GO) analysis. HBV, hLa and CK2 targets were predicted, respectively, by a computational method, followed by screening for matching gene symbols in the NCBI human sequences, GO, pathway and network analyses. hLa targets and respective networks in the viral mechanisms of HBV were obtained by the final integrative analysis. Thirty-seven hub genes were identified by overlap calculation, suggesting that hLa may play an important role in the development and progression of HBV through cytokine-cytokine receptor interaction, hematopoietic cell lineage, cell adhesion molecules (CAMs), antigen processing and presentation, Jak-STAT signalling pathway, natural killer cell-mediated cytotoxicity, apoptosis, T-cell receptor signalling pathway, complement and coagulation cascades, protein export and other pathways. Our data may help researchers to predict the molecular mechanisms of hLa in the development and progression of HBV through CK2 comprehensively. Moreover, the present data indicate that hLa targets may be a series of promising candidates for HBV.

Induction of immune-related gene expression in Ctenopharyngodon idella kidney cells by secondary metabolites from immunostimulatory Alcaligenes faecalis FY-3.

This study was undertaken to isolate active secondary metabolites from immunostimulatory Alcaligenes faecalis FY-3 and evaluate their activities using grass carp Ctenopharyngodon idella kidney (CIK) cells. By applying chromatography techniques and successive recrystallization, three purified metabolites were obtained and identified by spectral data (mass spectrometry and nuclear magnetic resonance) as: (1) phenylacetic acid, (2) p-hydroxyphenylacetylamide and (3) cyclo-(Gly-(L)-Pro). CIK cells were stimulated by different concentrations (1, 10 and 100 µg/ml) of the isolated compounds, and expression of MyD88, IL-1ß, TNF-α, type I-IFN and IL-8 genes at different time points (2, 8 and 24 h) post-stimulation was quantified by real-time PCR. The known immunostimulatory agent lipopolysaccharide (LPS) was used as a positive control. To analyse whether these compounds are toxic to the cells, the methyl tetrazolium assay was employed to measure changes in cell viability. The obtained results revealed that transcribing level of MyD88, an important adaptor molecule in toll-like receptor signalling pathway, was augmented remarkably by all the three isolated compounds and LPS as early as 2-h exposure. These compounds also induced gene expression of cytokines such as IL-1ß, TNF-α and type I-IFN. Under the experimental conditions, none of the test compounds is toxic to the CIK cells. These findings demonstrate that the immunostimulatory properties of the three metabolites [phenylacetic acid, p-hydroxyphenylacetylamide and cyclo-(Gly-(L)-Pro)] from A. faecalis FY-3 in CIK cells and highlight the potential of using these metabolites as immunostimulants in fish aquaculture.

Pubertal development timing in urban Chinese boys.

We describe current pubertal development in healthy urban Chinese boys. A cross-sectional study of the pubertal development of 18,807 urban Chinese boys aged from 3.50 to 18.49years was conducted between 2003 and 2005. Testicular volume was evaluated with a Prader orchidometer. Pubic hair development was assessed according to the Tanner method. Data on spermarche were collected using the status quo method. Probit analysis was used to calculate the median age and 95% CI at different stages of testicular development, pubic hair development and spermarche. By age 9, 12.99% of the boys had a testicular volume of 4mL or greater. The median age of onset of puberty defined as the age at attainment of testicular volume of 4mL or greater was 10.55 (95% CI 10.27-10.79) years. The median age for onset of pubic hair development (PH(2) ) and spermarche was 12.78 (95%CI 12.67-12.89) years and 14.05 (95%CI 13.80-14.32) years, respectively. Pubertal onset in urban Chinese boys is earlier than currently used clinical norms but their pubic hair development occurs relatively late in comparison with the reported data from numerous other countries. There is also evidence of a secular trend towards an earlier age of spermarche since 1979 in Chinese urban boys.

Novel cancer suppressor gene for esophageal cancer: manganese superoxide dismutase.

OBJECTIVES: To explore the expression of manganese superoxide dismutase (MnSOD) in esophageal squamous cell carcinoma (ESCC) and its relationship with clinicopathological characteristics and biological behavior. METHODS: On 45 patients with ESCC, immunohistochemistry (SP method), reverse transcription-polymerase chain reaction (RT-PCR), and Western blot were used to detect MnSOD protein and mRNA expression in ESCC and in its adjacent normal tissue 5 cm apart from the edge of cancer lesion and without documented microscopic invasive cancer. Meanwhile, the relationship between the pathological features of esophageal cancer and its biological behavior was analyzed. RESULTS: In ESCC and normal esophageal tissue, MnSOD protein expression was identified 31.1% (14/45) and 86.7% (31/45) (P= 0.000), respectively, with the relative expression levels of MnSOD mRNA 0.310 ± 0.036 and 0.482 ± 0.053 (P= 0.000), relatively. Western blot study showed that the relative expressions of MnSOD protein in cancer lesion and in adjacent normal tissue were 0.384 ± 0.038 and 0.766 ± 0.041, respectively (P= 0.000). With longer lesion, deeper invasion, and poorer differentiation, the expression of MnSOD would get lower, indicating that the levels of MnSOD protein and mRNA expression were closely related to the length of lesion, depth of invasion, and degree of differentiation in ESCC (P < 0.05). Nevertheless, the result showed no association with the presence of lymph node metastasis, cancer location, and macroscopic classification (P > 0.05). CONCLUSIONS: MnSOD protein and mRNA expression both decreased in ESCC, which may be related to carcinogenesis and the development of esophageal cancer. Therefore, detecting the expression of MnSOD in esophageal carcinoma would be of clinical significance in understanding its biological behavior and in guiding therapeutic strategy of esophageal cancer.

Comparative proteomic analysis of proteins influenced by melanin-concentrating hormone and melanin-concentrating hormone receptor 2 interaction.

Melanin-concentrating hormone receptor 2 (MCHR2), a second G protein-coupled receptor for melanin-concentrating hormone (MCH), has been known for many years. However, its physiological function is poorly understood. To identify the proteins involved in MCHR2 physiological function, a comparative proteomic analysis of protein expression in SH-SY5Y cells stably expressing human MCHR2 (SH-SY5Y-MCHR2) and control SH-SY5Y cells (SH-SY5Y-mock) - both treated with MCH - was conducted. Significant changes were observed in the expression of 34 proteins, including isocitrate dehydrogenase (NAD) subunit alpha, mitochondrial (IDH3A), phosphoenolpyruvate carboxykinase 1 (PCK1), 6-phosphofructo-2-kinase/fructose-2.6-biphosphatase 4 (PFKFB4), insulin-induced gene 2 protein (INSIG2), and acyl-coenzyme A thioesterase 8 (ACOT8). Among the proteins, IDH3A, PCK1, PFKFB4 increased significantly, and INSIG2, ACOT8 decreased significantly in experimental cells compared with control cells; these findings were further confirmed by semi-quantitative RT-PCR and Western blot analysis. The comparative proteome data may provide a valuable clue to further understand MCHR2 physiological function, and several differentially regulated proteins may be used as target proteins for the development of novel drugs.