Aim： Receptor-interacting protein 3 （RIP3） is involved in tumor necrosis factor receptor signaling, and results in NF-KB-mediated prosurvival signaling and programmed cell death. The aim of this ...study was to determine whether overexpression of the RIP3 gene could sensitize human breast cancer cells to parthenolide in vitro. Methods： The expression of RIP3 mRNA in human breast cancer cell lines （MCF-7, MDA-MB-231, MDA-MB-435 and T47D） was detected using RT-PCR. Both MDA-MB-231 and MCF-7 cells were transfected with RIP3 expression or blank vectors via lentivirus. Cell viability was measured with MTT assay; intracellular ROS level and cell apoptosis were analyzed using flow cytometry. Results： RIP3 mRNA expression was not detected in the four human breast cancer cell lines tested. However, the transfection induced higher levels of RIP3 protein in MCF-7 and MDA-MB-231 cells. Furthermore, overexpression of RIP3 decreased the IC50 values of parthenolide from 17.6 to 12.6 μmol/L in MCF-7 cells, and from 16.6 to 9.9 μmol/L in MDA-MB-231 cells. Moreover, overexpression of RIP3 significantly increased parthenolide-induced apoptosis and ROS accumulation in MCF-7 and MDA-MB-231 cells. Pretreatment with N-acetyl-cysteine abrogated the increased sensitivity of RIP3-transfected MCF-7 and MDA-MB-231 cells to parthenolide. Conclusion： Overexpression of RIP3 sensitizes MCF-7 and MDA-MB-231 breast cancer cells to parthenolide in vitro via intracellular ROS accumulation.
The overall survival of patients with hepatocellular carcinoma (HCC) remains poor, and the molecular pathogenesis remains incompletely defined in HCC. Here we report that increased expression of ...alphaB-Crystallin in human HCC predicts poor survival and disease recurrence after surgery. Multivariate analysis identifies alphaB-Crystallin expression as an independent predictor for postoperative recurrence and overall survival. We show that elevated expression of alphaB-Crystallin promotes HCC progression in vivo and in vitro. We demonstrate that alphaB-Crystallin overexpression fosters HCC progression by inducing epithelial-mesenchymal transition (EMT) in HCC cells through activation of the extracellular-regulated protein kinase (ERK) cascade, which can counteract the effect of sorafenib. alphaB-Crystallin complexes with and elevates 14-3-3zeta protein, leading to up-regulation of ERK1/2 activity. Moreover, overexpression of alphaB-Crystallin in HCC cells induces EMT progression through an ERK1/2/Fra-1/slug signaling pathway. Clinically, our data reveal that overexpression of both alphaB-Crystallin and 14-3-3zeta correlates with the HCC poorest survival outcomes, and sorafenib response is impaired in patients with alphaB-Crystallin overexpression. Conclusion: These data suggest that the alphaB-Crystallin-14-3-3zeta complex acts synergistically to promote HCC progression by constitutively activating ERK signaling. This study reveals alphaB-Crystallin as a potential therapeutic target for HCC and a biomarker for predicting sorafenib treatment response. (HEPATOLOGY 2013) PUBLICATION ABSTRACT
Along with the development of economy and society, type 2 diabetic mellitus (T2DM) has become one of the most common diseases at the global level. As one of the complications of T2DM, diabetic ...neuropathic pain (DNP) stubbornly and chronically affects the health and life of human beings. In the pain field, dorsal root ganglion (DRG) is generally considered as the first stage of the sensory pathway where the hyperexcitability of injured neurons is associated with different kinds of peripheral neuropathic pains. The abnormal electrophysiology is mainly due to the changed properties of voltage-gated sodium channels (VGSCs) and the increased sodium currents (I(Na)). Curcumin is an active ingredient extracted from turmeric and has been demonstrated to ameliorate T2DM and its various complications including DNP effectively. The present study demonstrates that the I(Na) of small-sized DRG neurons are significantly increased with the abnormal electrophysiological characteristics of VGSCs in type 2 diabetic neuropathic pain rats. And these abnormalities can be ameliorated efficaciously by a period of treatment with curcumin.
As one of the largest gene families, F-box domain proteins have important roles in regulating various devel- opmental processes and stress responses. In this study, we have investigated a rice F-box ...domain gene, MAIF1. The MAIF1 protein is mainly localized in the plasma membrane and nucleus. MAIF1 expression is induced rapidly and strongly by abscisic acid （ABA） and abiotic stresses. MAIF1 expression is also induced in root tips by sucrose, independent of its hy- drolytic hexose products, glucose and fructose, and the plant hormones auxin and cytokinin. Overexpression of MAIF1 reduces rice ABA sensitivity and abiotic stress tolerance and promotes rice root growth. These results suggest that MAIF1 is involved in multiple signaling pathways in regulating root growth. Growth restraint in plants is an acclimatization strategy against abiotic stress, Our results also suggest that MAIF1 plays the negative role in response to abiotic stress possibly by regulating root growth.
Abstract
Accumulating evidence suggests that long non-coding RNA (lncRNA) plays important roles in some malignant tumors. However, the mechanism underlying how lncRNA regulates hepatocellular ...carcinoma (HCC) process remains largely unknown. In this study, we explored the potential role of lncRNA 00607 as a novel tumor suppressor in HCC. In this study, we examined the regulation of lncRNA 00607 by the important inflammatory cytokine tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). We also determined the expression of LINC000607 in 159 HCC tumors and paired adjacent tissues. Effects of LINC000607 in HCC proliferation and apoptosis were examined in vitro in HCC cell lines and in vivo tumor xenografts. Furthermore, we also examine underlying mechanism by which lncRNA 00607 regulates NF-κB p65 and how LIN00607 exerts its tumor suppressor role in HCC. We found that lncRNA 00607 expression level is lower in HCC tumors compared with matched normal liver tissue, and its low expression predicts worse prognosis in HCC. Functionally, lncRNA 00607 overexpression leads to decreased HCC cell proliferation in vitro and in vivo, enhanced apoptosis and chemotherapeutic drug sensitivity. Mechanistically, lncRNA 00607 inhibits the p65 transcription by binding to the p65 promoter region, therefore contributing to increased p53 levels in HCC. Taken together, the findings of this study show that the TNF-α/IL-6-lncRNA 00607-NF-κB p65/p53 signaling axis represents a novel therapeutic avenue in cancer chemotherapy.
LINC00607 overexpression leads to decreased HCC cell proliferation in vitro and in vivo, enhanced apoptosis and chemotherapeutic drug sensitivity. Mechanistically, LINC00607 inhibits the p65 transcription by binding to the p65 promoter region, therefore contributing to increased p53 levels in HCC.
Two novel enediyne-derived natural products, amycolamycins A and B (1 and 2), were characterized from a locust-associated actinomycete Amycolatopsis sp. HCa4. Amycolamycins A and B contain a unique ...2-(cyclopentaainden-5-yl)oxirane core with suspected enediyne polyketide biosynthetic origin. Sequencing and analysis of the acm biosynthetic gene cluster allowed us to propose the biosynthetic pathway of 1 and 2. Moreover, amycolamycin A (1) was selectively cytotoxic to the M231 breast cancer cell line.
Fishbones are the most commonly ingested foreign bodies that cause gastrointestinal tract penetration.However,fishbones embedded in the gastrointestinal tract that lead to foreign body granulomas ...that mimic submucosal tumors are rare.Herein,we describe a56-year-old woman who presented with a 20-dayhistory of upper abdominal pain.Endoscopy revealed an elevated lesion in the gastric antrum.An abdominal computed tomography scan showed a mass in the gastric antrum and a linear calcified lesion in the mass.An endoscopic ultrasonography examination revealed a 3.9 cm×2.2 cm,irregular,hypoechoic mass with indistinct margins in the muscularis propria layer.The patient was initially diagnosed as having a submucosal tumor,and subsequent surgical resection showed that the lesion was a foreign body granuloma caused by an embedded fishbone.Our case indicated that the differential diagnosis of a foreign body granuloma should be considered in cases of elevated lesions in the gastrointestinal tract.
AIM： To investigate whether hepatitis B virus （HBV） could induce a hepatitis B virus core antigen （HBcAg）specific cytotoxic T lymphocyte （CTL） response in vitro by dendritic cells （DCs） transduced ...with lentiviral vector-encoding ubiquitinated hepatitis B virus core antigen （LV-Ub-HBcAg）.
METHODS： Recombinant LV-Ub-HBcAg were transfected into highly susceptible 293 T cells to obtain high virus titres, Bone marrow-derived DCs isolated from BALB/c mice were cultured with recombinant granulocyte-macrophage colony-stimulating factor and recombinant interleukin （IL）-4. LV-Ub-HBcAg, lentiviral vector-encoding hepatitis B virus core antigen （LV-HBcAg）, lentiviral vector （LV） or lipopolysaccharide were added to induce DC maturation, and the DC phenotypes were analyzed by flow cytometry. The level of IL-12 in the supernatant was detected by enzyme-linked immunosorbent assay （ELISA）. T lymphocytes were proliferated using Cell Counting Kit-8. DCs were cultured and induced to mature using different LVs, and co-cultured with allogeneic T cells to detect the secretion levels of IL-2, IL-4, IL-10and interferon-γ in the supernatants of T cells by ELISA. Intracellular cytokines of proliferative T cells were analyzed by flow cytometry, and specific CTL activity was measured by a lactate dehydrogenase release assay.
RESULTS： LV-Ub-HBcAg-induced DCs secreted more IL-12 and upregulated the expression of CD80, CD86 and major histocompatibility class I, DCs sensitised by different LVs effectively promoted cytokine secretion; the levels of IL-2 and interferon-y induced by LV-Ub- HBcAg were higher than those induced by LV-HBcAg, Compared with LV-HBcAg-transduced DCs, LV-Ub- HBcAg-transduced DCs more efficiently stimulated the proliferation of T lymphocytes and generated HBcAgspecific cytotoxic T lymphocytes.
CONCLUSION： LV-Ub-HBcAg effectively induced DC maturation. The mature DCs efficiently induced T cell polarisation to Thl and generated HBcAg-specific CTLs.
Background Previous brain imaging studies suggested that the brain activity underlying the perception of chronic pain may differ from that underlying acute pain. To investigate the brain regions ...involved in chronic spontaneous pain due to brachial plexus avulsion （BPA）, fluorine-18^fluorodeoxyglucose （18^F-FDG） positron emission tomography （PET） scanning was applied to determine the glucose metabolic changes in patients with pain due to BPA.
Methods Six right-handed patients with chronic spontaneous pain due to left-BPA and twelve right-handed age- and sex-matched healthy control subjects participated in the 18^F-FDG PET study. The patients were rated by visual analog scale （VAS） during scanning and Hamilton depression scale and Hamilton anxiety scale after scanning. Statistical parametric mapping 2 （SPM2） was applied for data analysis.
Results Compared with healthy subjects, the patients had significant glucose metabolism decreases in the right thalamus and SI （P 〈0.001, uncorrected）, and significant glucose metabolism increases in the right orbitofrontal cortex （OFC） （BAll）, left rostral insula cortex and left dorsolateral prefrontal cortex （DLPFC） （BA10/46） （P 〈0.001, uncorrected）.
Conclusion These findings suggest that the brain areas involved in emotion, attention and internal modulation of pain may be related to the chronic spontaneous pain due to BPA.
PDF
![[alpha]B-crystallin complex...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0270-9139/small "[alpha]B-crystallin complexes with 14-3-3[zeta] to induce epithelial-mesenchymal transition and resistance to sorafenib in hepatocellular carcinoma")
