Graptopetalum paraguayense

Role of inflammation-induced oxidative stress in the pathogenesis and progression of chronic inflammatory airways diseases has received increasing attention in recent years. Nuclear factor erythroid 2-related factor 2 is the primary transcription factor that regulates the expression of antioxidant and detoxifying enzymes. Graptopetalum paraguayense E. Walther, a vegetable consumed in Taiwan, has been used in folk medicine for protection against liver injury through elevating antioxidation. Recently, we found that gallic acid is an active compound of Graptopetalum paraguayense E. Walther, which has been reported to inhibit T-helper 2 cytokines. Currently, we assumed that Graptopetalum paraguayense E. Walther may potentially protect against ovalbumin-induced allergy and airway inflammation. Results demonstrated that Graptopetalum paraguayense E. Walther ethanolic extracts (GPE) clearly inhibited airway inflammation, mucus cell hyperplasia, and eosinophilia in OVA-challenged mice. Additionally, GPE also prevented T-cell infiltration and Th2 cytokines, including interleukin- (IL-)4, IL-5, and IL-13 generations in bronchial alveolar lavage fluid. The adhesion molecules ICAM-1 and VCAM-1 were substantially reduced by GPE treatment mediated by Nrf2 activation. Moreover, GPE attenuated GATA3 expression and inhibited Th2 signals of the T cells. These findings suggested that GPE ameliorated the development of airway inflammation through immune regulation

Oromotor variability in children with mild spastic cerebral palsy: a kinematic study of speech motor control

<p>Abstract</p> <p>Background</p> <p>Treating motor speech dysfunction in children with CP requires an understanding of the mechanism underlying speech motor control. However, there is a lack of literature in quantitative measures of motor control, which may potentially characterize the nature of the speech impairments in these children. This study investigated speech motor control in children with cerebral palsy (CP) using kinematic analysis.</p> <p>Methods</p> <p>We collected 10 children with mild spastic CP, aged 4.8 to 7.5 years, and 10 age-matched children with typical development (TD) from rehabilitation department at a tertiary hospital. All children underwent analysis of percentage of consonants correct (PCC) and kinematic analysis of speech tasks: poly-syllable (PS) and mono-syllable (MS) tasks using the Vicon Motion 370 system integrated with a digital camcorder. Kinematic parameters included spatiotemporal indexes (STIs), and average values and coefficients of variation (CVs) of utterance duration, peak oral opening displacement and velocity. An ANOVA was conducted to determine whether PCC and kinematic data significantly differed between groups.</p> <p>Results</p> <p>CP group had relatively lower PCCs (80.0-99.0%) than TD group (<it>p </it>= 0.039). CP group had higher STIs in PS speech tasks, but not in MS tasks, than TD group did (<it>p </it>= 0.001). The CVs of utterance duration for MS and PS tasks of children with CP were at least three times as large as those of TD children (<it>p </it>< 0.01). However, average values of utterance duration, peak oral opening displacement and velocity and CVs of other kinematic data for both tasks did not significantly differ between two groups.</p> <p>Conclusion</p> <p>High STI values and high variability on utterance durations in children with CP reflect deficits in relative spatial and/or especially temporal control for speech in the CP participants compared to the TD participants. Children with mild spastic CP may have more difficulty in processing increased articulatory demands and resulted in greater oromotor variability than normal children. The kinematic data such as STIs can be used as indices for detection of speech motor control impairments in children with mild CP and assessment of the effectiveness in the treatment.</p

Computational Procedure of Performance Assessment of Lifetime Index of Products for the Weibull Distribution with the Progressive First-Failure-Censored Sampling Plan

Process capability analysis has been widely applied in the field of quality control to monitor the performance of industrial processes. In practice, lifetime performance index CL is a popular means to assess the performance and potential of their processes, where L is the lower specification limit. This study will apply the large-sample theory to construct a maximum likelihood estimator (MLE) of CL with the progressive first-failure-censored sampling plan under the Weibull distribution. The MLE of CL is then utilized to develop a new hypothesis testing procedure in the condition of known L

Proopiomelanocortin gene delivery induces apoptosis in melanoma through NADPH oxidase 4-mediated ROS generation

AbstractHypoxia in the tumor microenvironment triggers differential signaling pathways for tumor survival. In this study, we characterize the involvement of hypoxia and reactive oxygen species (ROS) generation in the antineoplastic mechanism of proopiomelanocortin (POMC) gene delivery in a mouse B16-F10 melanoma model in vivo and in vitro. Histological analysis revealed increased TUNEL-positive cells and enhanced hypoxic activities in melanoma treated with adenovirus encoding POMC (Ad-POMC) but not control vector. Because the apoptotic cells were detected mainly in regions distant from blood vessels, it was hypothesized that POMC therapy might render melanoma cells vulnerable to hypoxic insult. Using a hypoxic chamber or cobalt chloride (CoCl2), we showed that POMC gene delivery elicited apoptosis and caspase-3 activation in cultured B16-F10 cells only under hypoxic conditions. The apoptosis induced by POMC gene delivery was associated with elevated ROS generation in vitro and in vivo. Blocking ROS generation using the antioxidant N-acetyl-l-cysteine abolished the apoptosis and caspase-3 activities induced by POMC gene delivery and hypoxia. We further showed that POMC-derived melanocortins, including α-MSH, β-MSH, and ACTH, but not γ-MSH, contributed to POMC-induced apoptosis and ROS generation during hypoxia. To elucidate the source of ROS generation, application of the NADPH oxidase inhibitor diphenyleneiodonium attenuated α-MSH-induced apoptosis and ROS generation, implicating the proapoptotic role of NADPH oxidase in POMC action. Of the NADPH oxidase isoforms, only Nox4 was expressed in B16-F10 cells, and Nox4 was also elevated in Ad-POMC-treated melanoma tissues. Silencing Nox4 gene expression with Nox4 siRNA suppressed the stimulatory effect of α-MSH-induced ROS generation and cell apoptosis during hypoxia. In summary, we demonstrate that POMC gene delivery suppressed melanoma growth by inducing apoptosis, which was at least partly dependent on Nox4 upregulation

Activation of Endothelial Cells by Antiphospholipid Antibodies—A Possible Mechanism Triggering Thrombosis in Patients with Antiphospholipid Syndrome

Antiphospholipid syndrome (APS) is an antibody-mediated hypercoagulable state characterized by recurrent venous and arterial thromboembolic events. The presence of serum antibodies are collectively termed as antiphospholipid antibodies (aPL) and is the hallmark of the disease. Interest in the pathogenesis has mostly been focused on the blood coagulation factor. However, endothelial cells might play an important role. When stimulated, cell membrane would flip to expose negatively charged phospholipids and activation markers such as adhesive molecules may appear. We consider that these changes may play an important role in the initiation of the thrombotic process when endothelial cells encounter aPL. In this study, we incubated human umbilical vein endothelial cells (HUVECs) with IgG isolated from patients with APS and found that the HUVECs were activated by the expression of negatively charged phospholipids, as shown by high annexin V binding and negative propidium iodide staining and by an increase in the level of intracellular cell adhesion molecule-1 on the cell surface. The above findings indicate that endothelial cells can be activated on exposure to aPL and trigger the thrombotic event

Stage-Specific Expression of TNFα Regulates Bad/Bid-Mediated Apoptosis and RIP1/ROS-Mediated Secondary Necrosis in Birnavirus-Infected Fish Cells

Infectious pancreatic necrosis virus (IPNV) can induce Bad-mediated apoptosis followed by secondary necrosis in fish cells, but it is not known how these two types of cell death are regulated by IPNV. We found that IPNV infection can regulate Bad/Bid-mediated apoptotic and Rip1/ROS-mediated necrotic death pathways via the up-regulation of TNFα in zebrafish ZF4 cells. Using a DNA microarray and quantitative RT-PCR analyses, two major subsets of differentially expressed genes were characterized, including the innate immune response gene TNFα and the pro-apoptotic genes Bad and Bid. In the early replication stage (0–6 h post-infection, or p.i.), we observed that the pro-inflammatory cytokine TNFα underwent a rapid six-fold induction. Then, during the early-middle replication stages (6–12 h p.i.), TNFα level was eight-fold induction and the pro-apoptotic Bcl-2 family members Bad and Bid were up-regulated. Furthermore, specific inhibitors of TNFα expression (AG-126 or TNFα-specific siRNA) were used to block apoptotic and necrotic death signaling during the early or early-middle stages of IPNV infection. Inhibition of TNFα expression dramatically reduced the Bad/Bid-mediated apoptotic and Rip1/ROS-mediated necrotic cell death pathways and rescued host cell viability. Moreover, we used Rip1-specific inhibitors (Nec-1 and Rip1-specific siRNA) to block Rip1 expression. The Rip1/ROS-mediated secondary necrotic pathway appeared to be reduced in IPNV-infected fish cells during the middle-late stage of infection (12–18 h p.i.). Taken together, our results indicate that IPNV triggers two death pathways via up-stream induction of the pro-inflammatory cytokine TNFα, and these results may provide new insights into the pathogenesis of RNA viruses

Lactiplantibacillus plantarum-encapsulated microcapsules prepared from okra polysaccharides improved intestinal microbiota in Alzheimer’s disease mice

BackgroundOkra contains a viscous substance rich in water-soluble material, including fibers, pectin, proteoglycans, gum, and polysaccharides. This study explored the use of okra polysaccharides by microorganisms and their potential to improve microbiota.MethodsThe regulation of microcapsules prepared from okra polysaccharides with or without L. plantarum encapsulation on intestinal microbiota was assessed through 16S metagenomic analysis and short-chain fatty acids (SCFAs) in AppNL-G-F/NL-G-F mice (Alzheimer’s disease; AD model).ResultsWe found that Lactobacillaceae and Lactobacillus were majorly regulated by microcapsules prepared from okra polysaccharides in AD mice. Similarly, microcapsules prepared from okra polysaccharides with L. plantarum encapsulation markedly elevated the abundance of Lactobacillaceae and Lactobacillus and increased SCFAs in AD mice.ConclusionOur results suggest that microcapsules prepared from okra polysaccharides with or without L. plantarum encapsulation may improve intestinal microbiota by elevating Lactobacillus levels in AD mice