Chinese herbal Jin-Ying-Tang attenuates the inflammatory response by inhibiting the activation of TLR4/MyD88/TRAF-6/NIK pathway at the mRNA level in LPS-stimulated mouse mammary epithelial cells

Introduction: The effects of Jin-Ying-Tang (JYT) on Toll-like Receptor 4 (TLR4) signalling transduction of lipopolysaccharide (LPS)-stimulated mouse mammary epithelial cells (MECs) in vitro were examined. Material and Methods: The cytotoxicity of JYT (0.06-62.50 mg/mL) on mouse MECs was determined by MTT assay. The MECs were co-cultured with LPS in the presence or absence of JYT (39.10 mu g/mL, 391 mu g/mL, 3910 mu g/mL). The concentrations of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) in the culture supernatants were detected by ELISA. The mRNA expression of TLR4 and downstream TLR4 signalling molecules such as myeloid differentiation factor 88 (MyD88), tumour necrosis factor receptor associated factor 6 (TRAF-6), inhibitor kappa B (I kappa B), and nuclear factor.B inducing kinase (NIK) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Results: The results showed that the IC50 of JYT on MECs was 12.25 mg/mL and JYT could significantly decrease the concentrations of IL-6 and TNF-alpha in LPS-stimulated MECs (P < 0.05). The mRNA expression of TLR4, MyD88, TRAF-6, I kappa B, and NIK was also significantly decreased when the LPS-stimulated MECs were cocultured at appropriate concentrations of JYT (P < 0.05, P < 0.01). Conclusion: These observations indicate a potential mechanism through which JYT attenuates the systemic inflammatory response to LPS-stimulated mouse mammary epithelial cells by inhibiting the activation of TLR4/MyD88/TRAF-6/NIK pathway at the mRNA level

Chinese herbal Jin-Ying-Tang attenuates the inflammatory response by inhibiting the activation of TLR4/MyD88/TRAF-6/NIK pathway at the mRNA level in LPS-stimulated mouse mammary epithelial cells

Introduction: The effects of Jin-Ying-Tang (JYT) on Toll-like Receptor 4 (TLR4) signalling transduction of lipopolysaccharide (LPS)-stimulated mouse mammary epithelial cells (MECs) in vitro were examined. Material and Methods: The cytotoxicity of JYT (0.06-62.50 mg/mL) on mouse MECs was determined by MTT assay. The MECs were co-cultured with LPS in the presence or absence of JYT (39.10 mu g/mL, 391 mu g/mL, 3910 mu g/mL). The concentrations of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) in the culture supernatants were detected by ELISA. The mRNA expression of TLR4 and downstream TLR4 signalling molecules such as myeloid differentiation factor 88 (MyD88), tumour necrosis factor receptor associated factor 6 (TRAF-6), inhibitor kappa B (I kappa B), and nuclear factor.B inducing kinase (NIK) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Results: The results showed that the IC50 of JYT on MECs was 12.25 mg/mL and JYT could significantly decrease the concentrations of IL-6 and TNF-alpha in LPS-stimulated MECs (P < 0.05). The mRNA expression of TLR4, MyD88, TRAF-6, I kappa B, and NIK was also significantly decreased when the LPS-stimulated MECs were cocultured at appropriate concentrations of JYT (P < 0.05, P < 0.01). Conclusion: These observations indicate a potential mechanism through which JYT attenuates the systemic inflammatory response to LPS-stimulated mouse mammary epithelial cells by inhibiting the activation of TLR4/MyD88/TRAF-6/NIK pathway at the mRNA level

Transcriptome analysis of Rpl11-deficient zebrafish model of Diamond-Blackfan Anemia

AbstractTo comprehensively reflect the roles of Rpl11 on the transcriptome of zebrafish model of Diamond-Blackfan Anemia (DBA), we performed whole-genome transcriptome sequencing on the Illumina Hi-Seq 2000 sequencing platform. Two different transcriptomes of zebrafish Rpl11-deficient and control Morpholino (Mo) embryos were collected and analyzed. The experimental design and methods, including sample preparation, RNA-Seq data evaluation and treatment, were described in details so that representative high-throughput sequencing data were acquired for assessing the actual impacts of Rpl11 on zebrafish embryos. We provided the accession number GSE51326 for easy access to the database

Secreted protein acidic and rich in cysteine (SPARC) is associated with nasopharyngeal carcinoma metastasis and poor prognosis

<p>Abstract</p> <p>Background</p> <p>The aim of the present study was to analyse the expression of Secreted protein acidic and rich in cysteine (SPARC) in nasopharyngeal carcinoma (NPC) specimens, and to evaluate its correlation with clinicopathologic features, including survival of patients with NPC</p> <p>Methods</p> <p>NPC tissue microarrays (TMAs) were constructed from Sun Yat-sen University Cancer Center (SYSUCC), another three centers on mainland China, Singapore and Hong Kong. Using quantitative RT-PCR and Western-blotting techniques, we detected mRNA and protein expression of SPARC in NPC cell lines and immortalized nasopharyngeal epithelial cells (NPECs) induced by Bmi-1 (NPEC2 Bmi-1). The difference of SPARC expression in the cell lines was tested using a <it>t</it>-test method. The relationship between the SPARC expression and clinicopathological data was assessed by chi-square. Survival analysis was estimated using the Kaplan-Meier approach with log-rank test. Univariate and multivariate analyses of clinical variables were performed using Cox proportional hazards regression models.</p> <p>Results</p> <p>The expression levels of SPARC mRNA and protein were markedly higher in NPC cell lines than in NPEC2 Bmi-1. Especially, the expression levels of SPARC mRNA and protein were much lower in the 6-10B than in the 5-8 F (<it>P </it>= 0.002, <it>P </it>= 0.001). SPARC immunostaining revealed cytoplasmic localization in NPC cells and no staining in the stroma and epithelium.</p> <p>In addition, high level of SPARC positively correlated with the status of distant metastasis (<it>P </it>= 0.001) and WHO histological classification (<it>P </it>= 0.023). NPC patients with high SPARC expression also had a significantly poorer prognosis than patients with low SPARC expression (log-rank test, <it>P </it>< 0.001), especially patients with advanced stage disease (log-rank, <it>P </it>< 0.001). Multivariate analysis suggested that the level of SPARC expression was an independent prognostic indicator for the overall survival of patients with NPC (<it>P </it>< 0.001).</p> <p>Conclusions</p> <p>SPARC expression is common in NPC patients. Our data shows that elevated SPARC expression is a potential unfavorable prognostic factor for patients with NPC.</p

HTRA1 variant increases risk to neovascular age-related macular degeneration in Chinese population

AbstractAge-related macular degeneration (AMD) is a leading cause of irreversible visual impairment in the world. Advanced AMD can be divided into wet AMD (choroidal neovascularization) and dry AMD (geographic atrophy, GA). Drusen is characterized by deposits in the macula without visual loss and is an early AMD sign in the Caucasian population. rs11200638 in the promoter of HTRA1 has recently been shown to increases the risk for wet AMD in both Caucasian and Hong Kong Chinese populations. In order to replicate these results in a different cohort, we genotyped rs11200638 for 164 Chinese patients (90 wet AMD and 74 drusen) and 106 normal controls in a Han Mainland Chinese cohort. The genotypes were compared using chi square analysis for an additive allelic model. rs11200638 was significantly associated with wet AMD (p=5.00×10−12). Unlike in the Caucasian population, the risk allele of rs11200638 was not associated with drusen in our Chinese population. These findings confirm the association of HTRA1 with wet AMD

MTHFR Gene Polymorphism Association With Psoriatic Arthritis Risk and the Efficacy and Hepatotoxicity of Methotrexate in Psoriasis.

Aims To assess whether MTHFR rs1801131 and rs1801133 SNPs are associated with concomitant psoriatic arthritis (PsA) and investigate the efficacy and hepatotoxicity of MTX in patients with psoriasis in the Han Chinese population. Methods This prospective, single-arm, interventional study recruited a total of 309 patients with psoriasis, 163 with psoriatic arthritis and 146 without psoriatic arthritis, who completed a 12-week MTX treatment and 1,031 healthy controls. Patients' characteristics including age, gender, disease duration, height, weight, smoking status, alcohol consumption, medical history, disease severity and liver function test results were accessed and recorded. Single nucleotide polymorphism (SNP) genotyping of rs1801131 and rs1801133 in the MTHFR gene was performed. Results The rs1801133 CC genotype was more frequent in patients with PsA than those with PsO and healthy controls (42.3% vs. 28.8% vs. 33.1%, p < 0.05). The 90% reduction from baseline PASI score (PASI 90) response rates to MTX were significantly higher in patients with the rs1801133 TT genotype than those with the CT and CC genotype (33.96% vs. 19.31% vs. 14.41%, OR = 2.76, p = 0.006). The rs1801133 CT+TT genotype was more frequent in PsA patients with abnormal liver function than in those with normal liver function (p < 0.05). In addition, patients with the rs1801131 CT genotype had lower PASI 75 response rates to MTX (OR = 0.49, p = 0.01), and lower risk of ALT elevation (OR = 0.46, p = 0.04). Conclusions This study provided some evidence for MTHFR polymorphism association with the risk of PsA and the efficacy and hepatotoxicity of the low-dose MTX in the Chinese population. Given the relatively small sample size and potentially missed diagnosis of PsA, the results from this study warrant further investigation

Selection and environmental adaptation along a path to speciation in the Tibetan frog Nanorana parkeri.

Tibetan frogs, Nanorana parkeri, are differentiated genetically but not morphologically along geographical and elevational gradients in a challenging environment, presenting a unique opportunity to investigate processes leading to speciation. Analyses of whole genomes of 63 frogs reveal population structuring and historical demography, characterized by highly restricted gene flow in a narrow geographic zone lying between matrilines West (W) and East (E). A population found only along a single tributary of the Yalu Zangbu River has the mitogenome only of E, whereas nuclear genes of W comprise 89-95% of the nuclear genome. Selection accounts for 579 broadly scattered, highly divergent regions (HDRs) of the genome, which involve 365 genes. These genes fall into 51 gene ontology (GO) functional classes, 14 of which are likely to be important in driving reproductive isolation. GO enrichment analyses of E reveal many overrepresented functional categories associated with adaptation to high elevations, including blood circulation, response to hypoxia, and UV radiation. Four genes, including DNAJC8 in the brain, TNNC1 and ADORA1 in the heart, and LAMB3 in the lung, differ in levels of expression between low- and high-elevation populations. High-altitude adaptation plays an important role in maintaining and driving continuing divergence and reproductive isolation. Use of total genomes enabled recognition of selection and adaptation in and between populations, as well as documentation of evolution along a stepped cline toward speciation

Discovery of a high-altitude ecotype and ancient lineage of Arabidopsis thaliana from Tibet

Arabidopsis thaliana (A. thaliana) has long been a model species for dicotyledon study, and was the first flowering plant to get its genome completed sequenced [1]. Although most wild A. thaliana are collected in Europe, several studies have found a rapid A. thaliana west-east expansion from Central Asia [2]. The Qinghai-Tibet Plateau (QTP) is close to Central Asia and known for its high altitude, unique environments and biodiversity [3]. However, no wild-type A. thaliana had been either discovered or sequenced from QTP. Studies on the A. thaliana populations collected under 2000 m asl have shown that the adaptive variations associated with climate and altitudinal gradients [4]. Hence a high-altitude A. thaliana provides a precious natural material to investigate the evolution and adaptation process. Here, we present the genome of a new ecotype of A. thaliana collected in the Gongga County, Tibet (4200 m asl) (Fig. 1a), to demonstrate its evolutionary history and adaptation to highaltitude regions

Nonlinear optical diode effect in a magnetic Weyl semimetal

Weyl semimetals have emerged as a promising quantum material system to discover novel electrical and optical phenomena, due to their combination of nontrivial quantum geometry and strong symmetry breaking. One crucial class of such novel transport phenomena is the diode effect, which is of great interest for both fundamental physics and modern technologies. In the electrical regime, giant electrical diode effect (the nonreciprocal transport) has been observed in Weyl systems. In the optical regime, novel optical diode effects have been theoretically considered but never probed experimentally. Here, we report the observation of the nonlinear optical diode effect (NODE) in the magnetic Weyl semimetal CeAlSi, where the magnetic state of CeAlSi introduces a pronounced directionality in the nonlinear optical second-harmonic generation (SHG). By physically reversing the beam path, we show that the measured SHG intensity can change by at least a factor of six between forward and backward propagation over a wide bandwidth exceeding 250 meV. Supported by density-functional theory calculations, we establish the linearly dispersive bands emerging from Weyl nodes as the origin of the extreme bandwidth. Intriguingly, the NODE directionality is directly controlled by the direction of magnetization. By utilizing the electronically conductive semimetallic nature of CeAlSi, we demonstrate current-induced magnetization switching and thus electrical control of the NODE in a mesoscopic spintronic device structure with current densities as small as 5 kA/cm$^2$. Our results advance ongoing research to identify novel nonlinear optical/transport phenomena in magnetic topological materials. The NODE also provides a way to measure the phase of nonlinear optical susceptibilities and further opens new pathways for the unidirectional manipulation of light such as electrically controlled optical isolators.Comment: 28 pages, 12 figure

Caveolin-1 enhances resveratrol-mediated cytotoxicity and transport in a hepatocellular carcinoma model

<p>Abstract</p> <p>Background</p> <p>Resveratrol (RES), an estrogen analog, is considered as a potential cancer chemo-preventive agent. However, it remains unclear how RES is transported into cells. In this study, we observed that Caveolin-1(CAV1) expression can increase the cytotoxic and pro-apoptotic activity of RES in a dose- and time-dependent manner both <it>in vitro </it>and <it>in vivo </it>in a Hepatocellular Carcinoma animal model.</p> <p>Methods</p> <p>High performance liquid chromatography (HPLC) demonstrated that RES intra-cellular concentration is increased about 2-fold in cells stably expressing CAV1 or CAVM1 (a scaffolding domain (81-101AA)-defective CAV1 mutant) compared to the untransduced human Hepatoblastoma cell line (HepG2) or after transduction with the green fluorescent protein (GFP) control vector. The increased intra-cellular transport of RES was abolished in cells stably expressing CAVM2 (a cholesterol shuttle domain (143-156AA)-defective CAV1 mutant) or CAVRNAi. In order to further characterize CAV1-dependent RES transport, we synthesized RES-dansyl chloride derivatives as fluorescent probes to visualize the transport process, which demonstrated a distribution consistent with that of CAV1 in HepG2 cells.</p> <p>Results</p> <p>In addition, RES endocytosis was not mediated by estrogen receptor (ER) α and β, as suggested by lack of competitive inhibition by estrogen or Tamoxifen. Pathway analysis showed that RES can up-regulate the expression of endogenous CAV1; this activates further the MAPK pathway and caspase-3 expression.</p> <p>Discussion</p> <p>This study provides novel insights about the role played by CAV1 in modulating cellular sensitivity to RES through enhancement of its internalization and trafficking.</p