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171.
172.
Background
Sjögren’s syndrome antigen B is expressed in the nucleus and surface membrane of human polymorphonuclear neutrophils and is released after cell death. However, its biological role is not clear. This study is aimed to investigate the effect of Sjögren’s syndrome antigen B on human polymorphonuclear neutrophils.Methods
Human recombinant Sjögren’s syndrome antigen B (rSSB) purified from E. coli was incubated with human polymorphonuclear neutrophils as well as retinoid acid-induced granulocytic differentiated HL-60 cells, HL-60 (RA). Interleukin (IL)-8 protein production and mRNA expressions were measured by enzyme-linked immunosorbent assay and quantitative-polymerase chain reaction, respectively. Uptake of fluorescein isothiocyanate (FITC)-rSSB was assessed by flow cytometry and fluorescence microscopy. Moreover, mitogen-activated protein kinase (MAPK) pathways and nuclear factor-kappaB activation were investigated.Results
Human rSSB stimulated IL-8 production from normal human neutrophils and HL-60 (RA) cells in a time- and dose-dependent manner. This IL-8-stimulated activity was blocked by chloroquine and NH4Cl, indicating that endosomal acidification is important for this effect. We found rSSB activated both MAPK pathway and nuclear factor-kappaB signaling to transcribe the IL-8 gene expression of cells. Furthermore, tumor necrosis factor-α exerted an additive effect and rSSB-anti-SSB immune complex exhibited a synergistic effect on rSSB-induced IL-8 production.Conclusions
Sjögren’s syndrome antigen B might act as an endogenous danger molecule to enhance IL-8 gene expression in human polymorphonuclear neutrophils. 相似文献173.
174.
Ching-Yu Yen Wei-Fan Chiang Shyun-Yeu Liu Chung-Chih Lin Kuo-An Liao Che-Yi Lin Wan-Fang Hsieh Yon-Chi Cheng Kai-Cheng Hsu Pin-Yen Lin Tai-Chi Chen I-Ling Lee Mei-Huei Lin Young-Chau Liu 《PloS one》2015,10(5)
Areca nut (AN) is a popular carcinogen used by about 0.6-1.2 billion people worldwide. Although AN contains apoptosis-inducing ingredients, we previously demonstrated that both AN extract (ANE) and its 30-100 kDa fraction (ANE 30-100K) predominantly induce autophagic cell death in both normal and malignant cells. In this study, we further explored the action mechanism of ANE 30-100K-induced autophagy (AIA) in Jurkat T lymphocytes and carcinoma cell lines including OECM-1 (mouth), CE81T/VGH (esophagus), SCC25 (tongue), and SCC-15 (tongue). The results showed that chemical- and small hairpin RNA (shRNA)-mediated inhibition of AMP-activated protein kinase (AMPK) resulted in the attenuation of AIA in Jurkat T but not in OECM-1 cells. Knockdown of Atg5 and Beclin 1 expressions ameliorated AIA in OECM-1/CE81T/VGH/Jurkat T and OECM-1/SCC25/SCC-15, respectively. Furthermore, ANE 30-100K could activate caspase-3 after inhibition of Beclin 1 expression in OECM-1/SCC25/SCC15 cells. Meanwhile, AMPK was demonstrated to be the upstream activator of the extracellular-regulated kinase (ERK) in Jurkat T cells, and inhibition of MEK attenuated AIA in Jurkat T/OECM-1/CE81T/VGH cells. Finally, we also found that multiple myeloma RPMI8226, lymphoma U937, and SCC15 cells survived from long-term non-cytotoxic ANE 30-100K treatment exhibited stronger resistance against serum deprivation through upregulated autophagy. Collectively, our studies indicate that Beclin-1 and Atg5 but not AMPK are commonly required for AIA, and MEK/ERK pathway is involved in AIA. Meanwhile, it is also suggested that long-term AN usage might increase the resistance of survived tumor cells against serum-limited conditions. 相似文献
175.
Yao-An Shen Chia-Yu Wang Yi-Tao Hsieh Yann-Jang Chen Yau-Huei Wei 《Cell cycle (Georgetown, Tex.)》2015,14(1):86-98
Cancer stem cells (CSCs) represent a subpopulation of tumor cells endowed with
self-renewal capacity and are considered as an underlying cause of tumor recurrence and
metastasis. The metabolic signatures of CSCs and the mechanisms involved in the regulation
of their stem cell-like properties still remain elusive. We utilized nasopharyngeal
carcinoma (NPC) CSCs as a model to dissect their metabolic signatures and found that CSCs
underwent metabolic shift and mitochondrial resetting distinguished from their
differentiated counterparts. In metabolic shift, CSCs showed a greater reliance on
glycolysis for energy supply compared with the parental cells. In mitochondrial resetting,
the quantity and function of mitochondria of CSCs were modulated by the biogenesis of the
organelles, and the round-shaped mitochondria were distributed in a peri-nuclear manner
similar to those seen in the stem cells. In addition, we blocked the glycolytic pathway,
increased the ROS levels, and depolarized mitochondrial membranes of CSCs, respectively,
and examined the effects of these metabolic factors on CSC properties. Intriguingly, the
properties of CSCs were curbed when we redirected the quintessential metabolic
reprogramming, which indicates that the plasticity of energy metabolism regulated the
balance between acquisition and loss of the stemness status. Taken together, we suggest
that metabolic reprogramming is critical for CSCs to sustain self-renewal, deter from
differentiation and enhance the antioxidant defense mechanism. Characterization of
metabolic reprogramming governing CSC properties is paramount to the design of novel
therapeutic strategies through metabolic intervention of CSCs. 相似文献
176.
The small GTPase Rab27a has been shown to control membrane trafficking and microvesicle transport pathways, in particular the secretion of exosomes. In the liver, high expression of Rab27a correlates with the development of hepatocellular carcinoma. We discovered that low abundance of Rab27a resulted in decreased hepatitis C virus (HCV) RNA and protein abundances in virus-infected cells. Curiously, both cell-associated and extracellular virus yield decreased in Rab27a depleted cells, suggesting that reduced exosome secretion did not cause the observed effect. Instead, Rab27a enhanced viral RNA replication by a mechanism that involves the liver-specific microRNA miR-122. Rab27a surrounded lipid droplets and was enriched in membrane fractions that harbor viral replication proteins, suggesting a supporting role for Rab27a in viral gene expression. Curiously, Rab27a depletion decreased the abundance of miR-122, whereas overexpression of miR-122 in Rab27a-depleted cells rescued HCV RNA abundance. Because intracellular HCV RNA abundance is enhanced by the binding of two miR-122 molecules to the extreme 5’ end of the HCV RNA genome, the diminished amounts of miR-122 in Rab27a-depleted cells could have caused destabilization of HCV RNA. However, the abundance of HCV RNA carrying mutations on both miR-122-binding sites and whose stability was supported by ectopically expressed miR-122 mimetics with compensatory mutations also decreased in Rab27a-depleted cells. This result indicates that the effect of Rab27a depletion on HCV RNA abundance does not depend on the formation of 5’ terminal HCV/miR-122 RNA complexes, but that miR-122 has a Rab27a-dependent function in the HCV lifecycle, likely the downregulation of a cellular inhibitor of HCV gene expression. These findings suggest that the absence of miR-122 results in a vulnerability not only to exoribonucleases that attack the viral genome, but also to upregulation of one more cellular factor that inhibit viral gene expression. 相似文献
177.
Yao-Li Chen Hui-Chuan Lin Kuo-Hua Lin Li-Si Lin Chia-En Hsieh Chih-Jan Ko Yu-Ju Hung Ping-Yi Lin 《PloS one》2015,10(3)
Background
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and liver resection is the only potential curative treatment option for those patients. Postoperative complications specific to elderly surgical patients such as delirium will be increasingly relevant in the coming decades. Herein, we aimed to investigate the risk factors for postoperative delirium in patients who have received hepatectomy for HCC.Methods
This is a single medical center observational study and the study subjects comprised 401 individuals who underwent liver resection for hepatocellular carcinoma during January 2009 to October 2013. Multivariate analysis was used to examine whether preoperative, intra-operative, or postoperative variables were associated with the development of delirium.Results
Of the 401 patients who underwent hepatectomy, 34 developed postoperative delirium (8.4%). In the majority of those patients, symptoms and signs of the syndrome occurred on postoperative day 2 and the mean duration of symptoms was 3.61 ± 3.71 days. Multivariate analysis revealed that advanced age (>71 years) [odds ratio (OR) = 1.133, 95% confidence interval (CI): 1.071–1.200, p<0.001], prolonged operative time (>190 minutes) (OR = 1.009, 95% CI: 1.000–1.017, p = 0.038), a decreased postoperative hemoglobin level (< 10.16 g/dL) (OR = 0.777, 95% CI: 0.613–0.983, p = 0.036), and history of hypnotic drug use (OR = 3.074, 95% CI: 1.045–9.039, p = 0.041) were independent risk factors for the development of postoperative delirium after hepatectomy.Conclusions
Although the mechanism of postoperative delirium is not well understood, numbers of studies have shown that patients with postoperative delirium tend to have prolonged hospital stay, worse postoperative outcome and an increased risk of short- and long-term mortality. In this study, we found that advanced age, prolonged operative time, postoperative low hemoglobin level and history of hypnotic drug use are independent risk factors for postoperative delirium. 相似文献178.
Hsin-Wei Chen Hui-Mei Hu Szu-Hsien Wu Chen-Yi Chiang Yu-Ju Hsiao Chia-Kai Wu Chun-Hsiang Hsieh Han-Hsuan Chung Pele Chong Chih-Hsiang Leng Chien-Hsiung Pan 《PloS one》2015,10(12)
Dengue is the leading cause of mosquito-borne viral infections and no vaccine is available now. Envelope protein domain III (ED3) is the major target for the binding of dengue virus neutralizing antibodies; however, the ED3-specifc T-cell response is less well understood. To investigate the T-cell responses to four serotypes of dengue virus (DENV-1 to 4), we immunized mice using either a tetravalent ED3-based DNA or protein vaccine, or combined both as a DNA prime-protein boost strategy (prime-boost). A significant serotype-dependent IFN-γ or IL-4 response was observed in mice immunized with either the DNA or protein vaccine. The IFN-γ response was dominant to DENV-1 to 3, whereas the IL-4 response was dominant to DENV-4. Although the similar IgG titers for the four serotypes were observed in mice immunized with the tetravalent vaccines, the neutralizing antibody titers varied and followed the order of 2 = 3>1>4. Interestingly, the lower IFN-γ response to DENV-4 is attributable to the immunodominance change between two CD4+ T-cell epitopes; one T-cell epitope located at E349-363 of DENV-1 to 3 was more immunogenic than the DENV-4 epitope E313-327. Despite DENV-4 specific IFN-γ responses were suppressed by immunodominance change, either DENV-4-specific IFN-γ or neutralizing antibody responses were still recalled after DENV-4 challenge and contributed to virus clearance. Immunization with the prime-boost elicited both IFN-γ and neutralizing antibody responses and provided better protection than either DNA or protein immunization. Our findings shed light on how ED3-based tetravalent dengue vaccines sharpen host CD4 T-cell responses and contribute to protection against dengue virus. 相似文献
179.
The subventricular zone (SVZ) is a proliferative region that provides neurons to olfactory bulb throughout life. The new neurons undergo cell migration from SVZ and travel until they reach their final destination. We previously showed in the early postnatal mouse a ventral migratory subpopulation from SVZ targets the Islands of Calleja (ICC) in the basal forebrain. However, unlike the well‐characterized rostral migratory stream, little is known about the guidance mechanisms operating in the ventrally directed migratory pathway. In this study, we examined the role of neurotransmitter γ‐aminobutyric acid (GABA) in SVZ‐derived progenitor ventral migration and the involvement of this neurotransmitter in the cytoarchitectual organization of dispersed cells into the tight clusters of the ICC. Our results show that the ventral SVZ cell migration rate was enhanced by GABA acting through a GABAA receptor and that GABA acts as a directional guidance cue for ventral migrating cells. Furthermore, disruption of GABA signaling inhibited the formation of Island clusters in vitro. Taken together, these data suggest that GABA is an important guidance and organizational cue for the Island of Calleja. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 791–804, 2015 相似文献
180.
Ming-Lun Yeh Cheng-Yuan Peng Chia-Yen Dai Hsueh-Chou Lai Chung-Feng Huang Ming-Yen Hsieh Jee-Fu Huang Shinn-Cherng Chen Zu-Yau Lin Ming-Lung Yu Wan-Long Chuang 《PloS one》2015,10(4)