Failure to respond to interferon-α 2a therapy is associated with increased hepatic iron levels in patients with chronic hepatitis C

Recent reports suggest the hepatic iron concentration (HIC) may influence the activity of hepatitis and the response to interferon (IFN) therapy in patients with chronic hepatitis C (CH-C). We have evaluated iron status in 28 patients with CH-C and determined if pretreatment iron status can predict the response to IFN-α therapy in these patients. Increased serum iron, transferrin saturation, and ferritin levels were observed in 3 (11%), 11 (39%), and 5 (18%) patients, respectively. Hepatic iron deposits were histologically detected in 17 (61%) patients, and 14 of them had stainable hepatocytic iron. However, all HIC values were within the normal range (203–1279 μg/g). Seven of 17 patients treated with IFN-α for 6 mo had normalization of serum transaminases and disappearance of serum HCV-RNA (responders). Nonresponders had a significantly higher median HIC compared with responders (710 vs 343 μg/g, respectively;p < 0.05). There was no significant difference in other pretreatment iron parameters, serum HCV-RNA level, or HCV-genotype between responders and nonresponders. In conclusion, mild hepatic iron accumulation occurs in patients with CH-C. Increased hepatic iron stores are associated with poor response to IFN therapy. Pretreatment HIC may be an additional host-specific parameter with a predictive value for responsiveness to IFN therapy, in addition to well-known predictive viral factors.     

慢性乙型肝炎舌红苔黄和舌淡苔白不同舌象的尿代谢组研究

目的：探索慢性乙型肝炎舌红苔黄和舌淡苔白不同舌象者的尿代谢差异指标,为中医舌象生物学物质基础微观辨证提供证据。方法：采用气相色谱／质谱联用（GC／MS ）技术方法获取慢性乙型肝炎舌红苔黄和舌淡苔白不同舌象者的尿液样本代谢指纹谱,用无监督的学习模式进行多变量统计分析,观察不同组别的人群之间是否存在“自然”的分类结构。利用有监督的学习模式进行数据分类模型的建立和检验,寻找造成样本聚集和离散的主要差异变量。利用商业化的代谢物谱库以及标准品数据库,进行物质鉴定。结果：慢性乙型肝炎舌红苔黄和舌淡苔白者在有监督的学习模式下具有良好的分开趋势,慢乙肝不同舌象者较健康者的差异代谢物谱主要与能量代谢、氨基酸代谢、核苷酸代谢以及肠道菌群代谢相关。结论：舌象是机体变化的重要窗口,不同舌象的外在表观潜在体内的代谢差异。     

The Reduction of Peripheral Blood CD4+ T Cell Indicates Persistent Organ Failure in Acute Pancreatitis

ObjectiveFew data are available on the potential role of inflammatory mediators and T lymphocytes in persistent organ failure (POF) in acute pancreatitis (AP). We conducted a retrospective study to characterize their role in the progression of POF in AP.MethodsA total of 69 AP patients presented within 24 hours from symptom onset developing organ failure (OF) on admission were included in our study. There were 39 patients suffering from POF and 30 from transient OF (TOF). On the 1st, 3rd and 7th days after admission, blood samples were collected for biochemical concentration monitoring including serum IL-1β, IL-6, TNF-α and high-sensitivity C-reactive protein (hs-CRP). The proportions of peripheral CD4⁺ and CD8⁺ T lymphocytes were assessed based on flow cytometry simultaneously.ResultsPatients with POF showed a significantly higher value of IL-1β and hs-CRP on day 7 compared with the group of TOF (P < 0.05). Proportions of CD4⁺ T cells on days 1, 3, 7 and CD4⁺ / CD8⁺ ratio on day 1 were statistically lower in the group of POF patients (P < 0.05). A CD4⁺ T cell proportion of 30.34% on day 1 predicted POF with an area under the curve (AUC) of 0.798, a sensitivity with 61.54% and specificity with 90.00%, respectively.ConclusionsThe reduction of peripheral blood CD4⁺ T lymphocytes is associated with POF in AP, and may act as a potential predictor.     

Prediction of Severe Acute Pancreatitis Using a Decision Tree Model Based on the Revised Atlanta Classification of Acute Pancreatitis

Objective

To develop a model for the early prediction of severe acute pancreatitis based on the revised Atlanta classification of acute pancreatitis.

Methods

Clinical data of 1308 patients with acute pancreatitis (AP) were included in the retrospective study. A total of 603 patients who were admitted to the hospital within 36 hours of the onset of the disease were included at last according to the inclusion criteria. The clinical data were collected within 12 hours after admission. All the patients were classified as having mild acute pancreatitis (MAP), moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) based on the revised Atlanta classification of acute pancreatitis. All the 603 patients were randomly divided into training group (402 cases) and test group (201 cases). Univariate and multiple regression analyses were used to identify the independent risk factors for the development of SAP in the training group. Then the prediction model was constructed using the decision tree method, and this model was applied to the test group to evaluate its validity.

Results

The decision tree model was developed using creatinine, lactate dehydrogenase, and oxygenation index to predict SAP. The diagnostic sensitivity and specificity of SAP in the training group were 80.9% and 90.0%, respectively, and the sensitivity and specificity in the test group were 88.6% and 90.4%, respectively.

Conclusions

The decision tree model based on creatinine, lactate dehydrogenase, and oxygenation index is more likely to predict the occurrence of SAP.     

MiR130b-Regulation of PPARγ Coactivator- 1α Suppresses Fat Metabolism in Goat Mammary Epithelial Cells

Fat metabolism is a complicated process regulated by a series of factors. microRNAs (miRNAs) are a class of negative regulator of proteins and play crucial roles in many biological processes; including fat metabolism. Although there have been some researches indicating that miRNAs could influence the milk fat metabolism through targeting some factors, little is known about the effect of miRNAs on goat milk fat metabolism. Here we utilized an improved miRNA detection assay, S-Poly-(T), to profile the expression of miRNAs in the goat mammary gland in different periods, and found that miR-130b was abundantly and differentially expressed in goat mammary gland. Additionally, overexpressing miR-130b impaired adipogenesis while inhibiting miR-130b enhanced adipogenesis in goat mammary epithelial cells. Utilizing 3’-UTR assay and Western Blot analusis, the protein peroxisome proliferator-activated receptor coactivator-1α (PGC1α), a major regulator of fat metabolism, was demonstrated to be a potential target of miR-130b. Interestingly, miR-130b potently repressed PGC1α expression by targeting both the PGC1α mRNA coding and 3’ untranslated regions. These findings have some insight of miR-130b in mediating adipocyte differentiation by repressing PGC1α expression and this contributes to further understanding about the functional significance of miRNAs in milk fat synthesis.     

RNA Interference-Based Transgenic Maize Resistant to Maize Dwarf Mosaic Virus

Maize dwarf mosaic virus (MDMV) is a widespread pathogenic virus that causes serious loss of yield in maize (Zea mays). RNA interference (RNAi) triggered by hairpin RNA (hpRNA) transcribed from a transgenic inverted-repeat sequence is an effective way to defend against viruses in plants. In this study, an hpRNA expression vector containing a sense arm and an antisense arm of 150 bp separated by an intron of the maize actin gene was constructed to target the P1 protein (protease) gene of MDMV and used to transform Agrobacterium tumefaciens strain EHA105. The transformed Agrobacterium strain was used to transform maize embryonic calli isolated from immature embryos by an improved culture technique. In all, 46 plants were regenerated after stringent hygromycin B selection, and 18 of them were certified to be positive by PCR amplification. Of these positive plants, 13 were grown to produce offspring, and nine were identified by Southern blotting to have the transgene integrated with one or two copies. The resistance of three T₂ lines was evaluated in a field trial of dual MDMV inoculation in two environments and was found to be improved compared with the non-transformed control. The disease indexes of the transgenic plant lines h2, 13, and h1 were not significantly different from the highly resistant control line H9-21. The viral titers of the inoculated plants were detected by double antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA), and the result was in accord with the resistance evaluated in the field trial. The addition of uniconazole S3307 (0.25 mg l⁻¹) and ABT root-promoting powder (0.5 mg l⁻¹) showed a significant improvement of hardening in regenerated plantlets, which were stronger and generated a better fibrous root system than the control. This improvement could facilitate the transgenic operation of maize.     

Ribosomal protein L6 promotes growth and cell cycle progression through upregulating cyclin E in gastric cancer cells

Our previous study revealed that human ribosomal protein L6 (RPL6) was upregulated in multidrug-resistant gastric cancer cells and over-expression of RPL6 could protect gastric cancer cells from drug-induced apoptosis. The present study was designed to explore the role of RPL6 in tumorigenesis and development of gastric cancer. The expression of RPL6 in gastric cancer tissues and normal gastric mucosa was evaluated by immunohistochemical staining. It was found RPL6 was expressed at a higher level in gastric cancer tissues than that in normal gastric mucosa. RPL6 was then genetically overexpressed or knocked down in human immortalized gastric mucosa epithelial GES cells. It was demonstrated that upregulation of RPL6 accelerated the growth and enhanced in vitro colony forming ability of GES cells whereas downregulation of RPL6 showed adverse effects. Moreover, over-expression of RPL6 could promote G1 to S phase transition of GES cells. It was further evidenced that upregulation of RPL6 resulted in elevated cyclin E expression while downregulation of RPL6 caused decreased cyclin E expression in GES cells. Taken together, these data indicated that RPL6 was overexpressed in human gastric cancer and its over-expression could promote cell growth and cell cycle progression at least through upregulating cyclin E expression.     

Overexpression of stearoyl-CoA desaturase-1 results in an increase of conjugated linoleic acid (CLA) and n-7 fatty acids in 293 cells

The effect of human SCD1 heterologous expression on cellular fatty acid synthesis was investigated in the current study. The SCD1 gene expression cassette and PGK-neomycin-selectable marker cassette were co-introduced into HEK 293 cells by electroporation, and subsequently, SCD1 expression was evaluated by fatty acid analysis. RT-PCR analysis indicated that the foreign SCD1 gene could be expressed in transformed cell lines. Total lipid analysis of the transformed cells fed with vaccenic acid (t11-18:1) as a substrate showed that SCD1 expression resulted in an increase in c9t11-CLA from 0.73-1.03% to 2.69-2.86% (p < 0.05) and that the conversion efficiency was elevated from 5.11-6.88% to 16.49-20.06% (p < 0.05). Surprisingly, the concentration of t10c12-CLA was also increased, from 0.10-0.41% to 1.35-1.69% in SCD1 cells (p < 0.05). SCD1 expression also resulted in a significant (p < 0.05) increase in palmitoleic acid (16:1 n-7) from 1.56-2.26% to 3.47-4.04% and cis-vaccenic acid (18:1 n-7) from 2.42-3.97% to 6.20-7.22%, and the corresponding conversion ratio of n-7 fatty acid was elevated from 12.01-16.70% to 22.62-24.13% (p < 0.05). This study demonstrates that the foreign SCD1 gene was expressed with high efficiency and induced elevated c9t11-CLA, t10c12-CLA, and n-7 fatty acid levels in mammalian cells.     

BAK1 and BKK1 regulate brassinosteroid-dependent growth and brassinosteroid-independent cell-death pathways

Brassinosteroids (BRs) are phytosteroid hormones controlling various physiological processes critical for normal growth and development. BRs are perceived by a protein complex containing two transmembrane receptor kinases, BRASSINOSTEROID INSENSITIVE 1 (BRI1) and BRI1-ASSOCIATED RECEPTOR KINASE 1 (BAK1) [1-3]. BRI1 null mutants exhibit a dwarfed stature with epinastic leaves, delayed senescence, reduced male fertility, and altered light responses. BAK1 null mutants, however, only show a subtle phenotype, suggesting that functionally redundant proteins might be present in the Arabidopsis genome. Here we report that BAK1-LIKE 1 (BKK1) functions redundantly with BAK1 in regulating BR signaling. Surprisingly, rather than the expected bri1-like phenotype, bak1 bkk1 double mutants exhibit a seedling-lethality phenotype due to constitutive defense-gene expression, callose deposition, reactive oxygen species (ROS) accumulation, and spontaneous cell death even under sterile growing conditions. Our detailed analyses demonstrate that BAK1 and BKK1 have dual physiological roles: positively regulating a BR-dependent plant growth pathway, and negatively regulating a BR-independent cell-death pathway. Both BR signaling and developmentally controlled cell death are critical to optimal plant growth and development, but the mechanisms regulating early events in these pathways are poorly understood. This study provides novel insights into the initiation and crosstalk of the two signaling cascades.