Protective effect of Dendrobium officinale polysaccharides on experimental Sjogren's syndrome

Sjogren's syndrome (SS), usually described as a chronic inflammation which results in xerostomia (dry mouth) and xerophthalmia (dry eyes). According to the theory of traditional Chinese medicine, body fluid impairment causes the dryness, inducing water secretion deficiency. Discovery of a family of water-specific membrane channel proteins, the aquaporins, provides an interesting molecular mechanism of water permeability and transportation which were found abnormal in tissues of SS patients. Thus, this dryness may lead to the dysfunction in organs as various systematic manifestations. We established an autoallergic mouse model in vivo, and human salivary gland cell line A-253 in vitro. Polysaccharides of Dendrobium officinale (DP) were administrated as treatment, which was described to nourish yin and promote the body fluid. Results showed that immunization with SG autoantigen induced decrease of body weight and increased water intake, decreased AQP5 expression in a series of organs related to body fluid. Sera from model mice induced apoptosis of A-253 cells with activation of caspase-3. Administration of DP could reverse these pathological changes in both the animal and cell model. Thus, DP may be a promising candidate for the treatment of SS by up-regulating the expression of AQP-5 and protecting cells from apoptosis. © 2010 The Berkeley Electronic Press. All rights reserved.published_or_final_versio

Comprehensive and Holistic Analysis of HT-29 Colorectal Cancer Cells and Tumor-Bearing Nude Mouse Model: Interactions Among Fractions Derived From the Chinese Medicine Formula Tian Xian Liquid in Effects on Human Colorectal Carcinoma

The Chinese medicine formula Tian Xian Liquid (TXL) has been used clinically for cancer therapy in China for more than 25 years. However, the comprehensive and holistic effects of its bioactive fractions for various antitumor therapeutic effects have not been unraveled. This is the first study to scientifically elucidate the holistic effect of Chinese medicine formula for treating colon cancer, hence allowing a better understanding of the essence of Chinese medicine formula, through the comparison of the actions of TXL and its functional constituent fractions, including ethyl acetate (EA), butanol (BU), and aqueous (WA) fractions. Tissue-specific proliferative/antiproliferative effects of these fractions on human colorectal carcinoma HT-29 cells and splenocytes were studied by using the MTT assay. Their modulations on the expression of markers of antiproliferation, antimetastasis, reversion of multidrug resistance in treated HT-29 cells were examined with real-time polymerase chain reaction and Western blot analysis, and their modulations in a xenografted nude mouse model were examined by Western blot analysis. Results revealed that EA fraction slightly inhibited the proliferation of HT-29 cells, but tissue-specifically exerted the most potent antiproliferative effect on splenocytes. On the contrary, only TXL and BU fraction tissue-specifically contributed to the proliferation of splenocytes, but inhibited the proliferation of HT-29 cells. WA fraction exerted the most potent antiproliferative effect on HT-29 cells and also the strongest inhibitory action on tumor size in the nude mouse model in our previous study. In the HT-29 model, TXL and WA fraction exerted the most pronounced effect on upregulation of p21 mRNA and protein; TXL, and EA and WA fractions exerted the effect on downregulation of G1 phase cell cycle protein, cyclin D1 mRNA and protein; EA and BU fractions exerted the most prominent anti-invasive effect on anti-invasion via downregulation of MMP-1 mRNA; TXL potently reversed most multidrug resistance via downregulation of MDR-1 protein. In conclusion, the comprehensive and holistic effects of TXL were demonstrated with (a) mutual accentuation and mutual enhancement, (b) mutual counteraction and mutual suppression, and (c) mutual antagonism among the 3 constituent fractions. Moreover, the design of the present study may lead to further development of more tissue-specific effective drugs with minimal side effects for clinical use in combating carcinoma.published_or_final_versio

Protective effect of Dendrobium officinale polysaccharides on experimental Sjogren's syndrome

Sjogren's syndrome (SS), usually described as a chronic inflammation which results in xerostomia (dry mouth) and xerophthalmia (dry eyes). According to the theory of traditional Chinese medicine, body fluid impairment causes the dryness, inducing water secretion deficiency. Discovery of a family of water-specific membrane channel proteins, the aquaporins, provides an interesting molecular mechanism of water permeability and transportation which were found abnormal in tissues of SS patients. Thus, this dryness may lead to the dysfunction in organs as various systematic manifestations. We established an autoallergic mouse model in vivo, and human salivary gland cell line A-253 in vitro. Polysaccharides of Dendrobium officinale (DP) were administrated as treatment, which was described to nourish yin and promote the body fluid. Results showed that immunization with SG autoantigen induced decrease of body weight and increased water intake, decreased AQP5 expression in a series of organs related to body fluid. Sera from model mice induced apoptosis of A-253 cells with activation of caspase-3. Administration of DP could reverse these pathological changes in both the animal and cell model. Thus, DP may be a promising candidate for the treatment of SS by up-regulating the expression of AQP-5 and protecting cells from apoptosis. © 2010 The Berkeley Electronic Press. All rights reserved.published_or_final_versio

Adding control to arbitrary unknown quantum operations

While quantum computers promise significant advantages, the complexity of quantum algorithms remains a major technological obstacle. We have developed and demonstrated an architecture-independent technique that simplifies adding control qubits to arbitrary quantum operations-a requirement in many quantum algorithms, simulations and metrology. The technique is independent of how the operation is done, does not require knowledge of what the operation is, and largely separates the problems of how to implement a quantum operation in the laboratory and how to add a control. We demonstrate an entanglement-based version in a photonic system, realizing a range of different two-qubit gates with high fidelity.Comment: 9 pages, 8 figure

Modelling of macrosegregation in direct chill casting considering columnar-to-equiaxed transition using 3-phase Eulerian approach

A 3-phase Eulerian approach is used to model the macrosegregation during solidification in direct chill (DC) casting of binary bronze (Cu-Sn). The three phases are the melt, the solidifying columnar dendrites and the equiaxed grains. The thermodynamic information of Cu-Sn is included based on published thermodynamic data, which are coupled with the 3-phase solidification model. The occurrence of columnar-to-equiaxed transition (CET), phase interactions, feeding flow, equiaxed sedimentation and their influence on macrosegregation are considered in the model. The model is applied to a laboratory DC casting process of bronze as a benchmark to demonstrate the model potentials. The simulation results of mixed columnar and equiaxed solidification as well as the formation of macrosegregation are presented. The focus of this work is to analyze and discuss the macrosegregation mechanisms by different flow including feeding flow and crystal sedimentation

A metabolite-derived protein modification integrates glycolysis with KEAP1-NRF2 signalling.

Mechanisms that integrate the metabolic state of a cell with regulatory pathways are necessary to maintain cellular homeostasis. Endogenous, intrinsically reactive metabolites can form functional, covalent modifications on proteins without the aid of enzymes1,2, and regulate cellular functions such as metabolism3-5 and transcription6. An important 'sensor' protein that captures specific metabolic information and transforms it into an appropriate response is KEAP1, which contains reactive cysteine residues that collectively act as an electrophile sensor tuned to respond to reactive species resulting from endogenous and xenobiotic molecules. Covalent modification of KEAP1 results in reduced ubiquitination and the accumulation of NRF27,8, which then initiates the transcription of cytoprotective genes at antioxidant-response element loci. Here we identify a small-molecule inhibitor of the glycolytic enzyme PGK1, and reveal a direct link between glycolysis and NRF2 signalling. Inhibition of PGK1 results in accumulation of the reactive metabolite methylglyoxal, which selectively modifies KEAP1 to form a methylimidazole crosslink between proximal cysteine and arginine residues (MICA). This posttranslational modification results in the dimerization of KEAP1, the accumulation of NRF2 and activation of the NRF2 transcriptional program. These results demonstrate the existence of direct inter-pathway communication between glycolysis and the KEAP1-NRF2 transcriptional axis, provide insight into the metabolic regulation of the cellular stress response, and suggest a therapeutic strategy for controlling the cytoprotective antioxidant response in several human diseases

Seatbelt use and risk of major injuries sustained by vehicle occupants during motor-vehicle crashes: A systematic review and meta-analysis of cohort studies

BackgroundIn 2004, a World Health Report on road safety called for enforcement of measures such as seatbelt use, effective at minimizing morbidity and mortality caused by road traffic accidents. However, injuries caused by seatbelt use have also been described. Over a decade after publication of the World Health Report on road safety, this study sought to investigate the relationship between seatbelt use and major injuries in belted compared to unbelted passengers.MethodsCohort studies published in English language from 2005 to 2018 were retrieved from seven databases. Critical appraisal of studies was carried out using the Scottish Intercollegiate Guidelines Network (SIGN) checklist. Pooled risk of major injuries was assessed using the random effects meta-analytic model. Heterogeneity was quantified using I-squared and Tau-squared statistics. Funnel plots and Egger's test were used to investigate publication bias. This review is registered in PROSPERO (CRD42015020309).ResultsEleven studies, all carried out in developed countries were included. Overall, the risk of any major injury was significantly lower in belted passengers compared to unbelted passengers (RR 0.47; 95%CI, 0.29 to 0.80; I-2=99.7; P=0.000). When analysed by crash types, belt use significantly reduced the risk of any injury (RR 0.35; 95%CI, 0.24 to 0.52). Seatbelt use reduces the risk of facial injuries (RR=0.56, 95% CI=0.37 to 0.84), abdominal injuries (RR=0.87; 95% CI=0.78 to 0.98) and, spinal injuries (RR=0.56, 95% CI=0.37 to 0.84). However, we found no statistically significant difference in risk of head injuries (RR=0.49; 95% CI=0.22 to 1.08), neck injuries (RR=0.69: 95%CI 0.07 to 6.44), thoracic injuries (RR 0.96, 95%CI, 0.74 to 1.24), upper limb injuries (RR=1.05, 95%CI 0.83 to 1.34) and lower limb injuries (RR=0.77, 95%CI 0.58 to 1.04) between belted and non-belted passengers.ConclusionIn sum, the risk of most major road traffic injuries is lower in seatbelt users. Findings were inconclusive regarding seatbelt use and susceptibility to thoracic, head and neck injuries during road traffic accidents. Awareness should be raised about the dangers of inadequate seatbelt use. Future research should aim to assess the effects of seatbelt use on major injuries by crash type

Salt-inducible kinases (SIKs) regulate TGFβ-mediated transcriptional and apoptotic responses

The signalling pathways initiated by members of the transforming growth factor-β (TGFβ) family of cytokines control many metazoan cellular processes, including proliferation and differentiation, epithelial-mesenchymal transition (EMT) and apoptosis. TGFβ signalling is therefore strictly regulated to ensure appropriate context-dependent physiological responses. In an attempt to identify novel regulatory components of the TGFβ signalling pathway, we performed a pharmacological screen by using a cell line engineered to report the endogenous transcription of the TGFβ-responsive target gene PAI-1. The screen revealed that small molecule inhibitors of salt-inducible kinases (SIKs) attenuate TGFβ-mediated transcription of PAI-1 without affecting receptor-mediated SMAD phosphorylation, SMAD complex formation or nuclear translocation. We provide evidence that genetic inactivation of SIK isoforms also attenuates TGFβ-dependent transcriptional responses. Pharmacological inhibition of SIKs by using multiple small-molecule inhibitors potentiated apoptotic cell death induced by TGFβ stimulation. Our data therefore provide evidence for a novel function of SIKs in modulating TGFβ-mediated transcriptional and cellular responses.</p

Neurogenesis Drives Stimulus Decorrelation in a Model of the Olfactory Bulb

The reshaping and decorrelation of similar activity patterns by neuronal networks can enhance their discriminability, storage, and retrieval. How can such networks learn to decorrelate new complex patterns, as they arise in the olfactory system? Using a computational network model for the dominant neural populations of the olfactory bulb we show that fundamental aspects of the adult neurogenesis observed in the olfactory bulb -- the persistent addition of new inhibitory granule cells to the network, their activity-dependent survival, and the reciprocal character of their synapses with the principal mitral cells -- are sufficient to restructure the network and to alter its encoding of odor stimuli adaptively so as to reduce the correlations between the bulbar representations of similar stimuli. The decorrelation is quite robust with respect to various types of perturbations of the reciprocity. The model parsimoniously captures the experimentally observed role of neurogenesis in perceptual learning and the enhanced response of young granule cells to novel stimuli. Moreover, it makes specific predictions for the type of odor enrichment that should be effective in enhancing the ability of animals to discriminate similar odor mixtures

From presence to consciousness through virtual reality

Immersive virtual environments can break the deep, everyday connection between where our senses tell us we are and where we are actually located and whom we are with. The concept of 'presence' refers to the phenomenon of behaving and feeling as if we are in the virtual world created by computer displays. In this article, we argue that presence is worthy of study by neuroscientists, and that it might aid the study of perception and consciousness