8-Prenylkaempferol Suppresses Influenza A Virus-Induced RANTES Production in A549 Cells via Blocking PI3K-Mediated Transcriptional Activation of NF-κB and IRF3

8-Prenylkaempferol (8-PK) is a prenylflavonoid isolated from Sophora flavescens, a Chinese herb with antiviral and anti-inflammatory properties. In this study, we investigated its effect on regulated activation, normal T cell expressed and secreted (RANTES) secretion by influenza A virus (H1N1)-infected A549 alveolar epithelial cells. Cell inoculation with H1N1 evoked a significant induction in RANTES accumulation accompanied with time-related increase in nuclear translocation of nuclear factor-κB (NF-κB) and interferon regulatory factor 3 (IRF-3), but showed no effect on c-Jun phosphorylation. 8-PK could significantly inhibit not only RANTES production but also NF-κB and IRF-3 nuclear translocation. We had proved that both NF-κB and IRF-3 participated in H1N1-induced RANTES production since NF-κB inhibitor pyrrolidinedithio carbamate (PDTC) and IRF-3 siRNA attenuated significantly RANTES accumulation. H1N1 inoculation also increased PI3K activity as well as Akt phosphorylation and such responsiveness were attenuated by 8-PK. In the presence of wortmannin, nuclear translocation of NF-κB and IRF3 as well as RANTES production by H1N1 infection were all reversed, demonstrating that PI3K-Akt pathway is essential for NF-κB- and IRF-3-mediated RANTES production in A549 cells. Furthermore, 8-PK but not wortmannin, prevented effectively H1N1-evoked IκB degradation. In conclusion, 8-PK might be an anti-inflammatory agent for suppressing influenza A virus-induced RANTES production acts by blocking PI3K-mediated transcriptional activation of NF-κB and IRF-3 and in part by interfering with IκB degradation which subsequently decreases NF-κB translocation

3,4-Di-O-Caffeoylquinic Acid Inhibits Angiotensin-II-Induced Vascular Smooth Muscle Cell Proliferation and Migration by Downregulating the JNK and PI3K/Akt Signaling Pathways

We previously reported 3,4-di-O-caffeoylquinic acid (CQC) protected vascular endothelial cells against oxidative stress and restored impaired endothelium-dependent vasodilatation. Here, we further investigated its anti-atherosclerotic effect against angiotensin II (Ang II) evoked proliferation and migration of cultured rat vascular smooth muscle cells (rVSMC). The results showed CQC (1–20 μM) clearly inhibited Ang-II-stimulated BrdU incorporation and cell migration of rVSMC in a concentration-dependent manner but without significant cytotoxicity. Western blot analysis revealed Ang II increased the phosphorylation levels of Akt and mitogen-activated protein kinases (MAPKs;p38, ERK1/2 and JNK) in rVSMC. In the presence of phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin and three individual MAPK inhibitors SB203580, PD98059 and SP600125, both Ang-II-induced cell proliferation and migration were significantly attenuated, although to differing extents, suggesting the PI3K and MAPK signal pathways all participated in regulating rVSMC proliferation and migration. Also, the CQC pretreatment markedly suppressed Ang-II-induced phosphorylation of Akt and JNK rather than ERK1/2, although it failed to affect p38 phosphorylation. In conclusion, our data demonstrate CQC may act by down-regulating Akt, JNK and part of the ERK1/2 pathways to inhibit Ang-II-induced rVSMC proliferation and migration. The anti-atherosclerotic effect of CQC is achieved either by endothelial cells protection or by VSMC proliferation/migration inhibition, suggesting this compound may be useful in preventing vascular diseases

One-stage reconstruction of large lower lip defect and oral competence with free composite anterolateral thigh-tensor fasciae latae flap

SummaryReconstruction for a large lower lip defect is a challenge to reconstructive surgeons. The most challenging problem is to maintain oral competence and prevent sialorrhea. We present three cases of such a defect reconstructed with composite anterolateral thigh-tensor fascia lata free flaps in one stage. The patients reported in this communication had advanced squamous cell carcinoma in the lower lip. A large lower lip defect (>90%) resulted in each case from wide excision of the tumor. A composite anterolateral thigh-tensor fasciae latae free flap was used to reconstruct the defect and to restore the dynamic oral competence in one stage. A tensor fasciae latae sling was attached by two strips sutured together to the upper orbicularis oris muscle in the first case. The four-strip method, a modification of the method described by Serkan,1 was adopted in the second case. The upper two strips bilaterally sutured to the orbicularis oris muscles in a mode somewhat different from Serkan’s method. The tensor fasciae latae sling was attached by two strips sutured to the periosteum of both zygomatic eminences in the third case. The tensor fasciae latae sling of Case 1 failed with persistent sialorrhea. The second case had good oral competence and comprehensible speech ability without sialorrhea. The third case had an acceptable result before he was lost to follow-up. A composite anterolateral thigh-tensor fasciae latae free flap is a good choice for a large lower lip defect to achieve oral competence reconstruction in one stage. Simultaneous dynamic and static suspensions are suggested to maintain oral competence and prevent sialorrhea

Anti-inflammatory and anti-infectious effects of Evodia rutaecarpa (Wuzhuyu) and its major bioactive components

This article reviews the anti-inflammatory relative and anti-infectious effects of Evodia rutaecarpa and its major bioactive components and the involvement of the nitric oxide synthases, cyclooxygenase, NADPH oxidase, nuclear factor kappa B, hypoxia-inducible factor 1 alpha, reactive oxygen species, prostaglandins, tumor necrosis factor, LIGHT, amyloid protein and orexigenic neuropeptides. Their potential applications for the treatment of endotoxaemia, obesity, diabetes, Alzheimer's disease and their uses as cardiovascular and gastrointestinal protective agents, analgesics, anti-oxidant, anti-atherosclerosis agents, dermatological agents and anti-infectious agents are highlighted. Stimulation of calcitonin gene-related peptide release may partially explain the analgesic, cardiovascular and gastrointestinal protective, anti-obese activities of Evodia rutaecarpa and its major bioactive components

Intercellular calcium signaling in a gap junction-coupled cell network establishes asymmetric neuronal fates in C. elegans

The C. elegans left and right AWC olfactory neurons specify asymmetric subtypes, one default AWC(OFF) and one induced AWC(ON), through a stochastic, coordinated cell signaling event. Intercellular communication between AWCs and non-AWC neurons via a NSY-5 gap junction network coordinates AWC asymmetry. However, the nature of intercellular signaling across the network and how individual non-AWC cells in the network influence AWC asymmetry is not known. Here, we demonstrate that intercellular calcium signaling through the NSY-5 gap junction neural network coordinates a precise 1AWC(ON)/1AWC(OFF) decision. We show that NSY-5 gap junctions in C. elegans cells mediate small molecule passage. We expressed vertebrate calcium-buffer proteins in groups of cells in the network to reduce intracellular calcium levels, thereby disrupting intercellular communication. We find that calcium in non-AWC cells of the network promotes the AWC(ON) fate, in contrast to the autonomous role of calcium in AWCs to promote the AWC(OFF) fate. In addition, calcium in specific non-AWCs promotes AWC(ON) side biases through NSY-5 gap junctions. Our results suggest a novel model in which calcium has dual roles within the NSY-5 network: autonomously promoting AWC(OFF) and non-autonomously promoting AWC(ON)

Use of Seasonal Influenza Vaccination and Its Associated Factors among Elderly People with Disabilities in Taiwan: A Population-Based Study

Influenza immunization among elderly people with disabilities is a critical public health concern; however, few studies have examined the factors associated with vaccination rates in non-Western societies.By linking the National Disability Registration System and health service claims dataset from the National Health Insurance program, this population-based study investigated the seasonal influenza vaccination rate among elderly people with disabilities in Taiwan (N = 283,172) in 2008. A multivariate logistic regression analysis was conducted to adjust for covariates.Nationally, only 32.7% of Taiwanese elderly people with disabilities received influenza vaccination. The strongest predictor for getting vaccinated among older Taiwanese people with disabilities was their experience of receiving an influenza vaccination in the previous year (adjusted odds ratio [AOR] = 6.80, 95% confidence interval [CI]: 6.67-6.93). Frequent OPD use (AOR = 1.85, 95% CI: 1.81-1.89) and undergoing health examinations in the previous year (AOR = 1.66, 95% CI: 1.62-1.69) also showed a moderate and significant association with receiving an influenza vaccination.Although free influenza vaccination has been provided in Taiwan since 2001, influenza immunization rates among elderly people with disabilities remain low. Policy initiatives are required to address the identified factors for improving influenza immunization rates among elderly people with disabilities

Analyzing 13 Years of Cetacean Strandings: Multiple Stressors to Cetaceans in Taiwanese Waters and Their Implications for Conservation and Future Research

This study summarizes the postmortem investigations of 73 cetaceans stranded on the coast of Taiwan between 2001 and 2013, including 51 Delphinidae, 17 Kogiidae, 3 Ziphiidae, 1 Physeteridae, and 1 Balaenopteridae. Of these, eight (11%) were categorized into direct human-related strandings, including fisheries interaction (bycatch), vessel collision and other anthropogenic-related pathology. Gastrointestinal foreign bodies were found in eight individuals (11%). Most of the bacteria isolated from stranded dolphins were zoonotic pathogens including extended-spectrum β-lactamases Escherichia coli, which indicates waste pollution from land. Severe parasite infestation was found in 36 of the cases (49%), which suggests that the immune function could be compromised. Thirty-eight cases (52%) were diagnosed with myocardial patchy fibrosis or dilated cardiomyopathy. The evidence shown here indicates that cetaceans around Taiwanese waters may suffer from multiple stressors. This study provides baseline data for the health assessment of cetacean populations in Taiwan, which may ultimately provide recommendations for future cetacean conservation and research throughout the western Pacific