Inhibitory effects of (-)-epigallocatechin-3-gallate on melanogenesis in ultraviolet A-induced B16 murine melanoma cell

Purpose: To investigate the anti-melanogenesis effect of green tea compound, (-)-epigallocatechin-3- gallate (EGCG), on B16 murine melanoma cell irradiated by ultraviolet A (UVA) in the search for natural skin-lightening alternative agents.Methods: B16 murine melanoma cells by UVA (9.0 J/cm2) for 0 to 32 min and then incubated in Dulbecco's Modified Eagle's Medium (DMEM) with EGCG (0-200 μg/mL) for 2 days. Cell viability was determined by MTT method and cell protein was quantified using a PA102 Bradford protein assay kit. Activity of tyrosinase (TRY) was determined based on the oxidation rate of 3,4-dihydroxy phenylalanine (DOPA). The ultra-structure of the melanosomes was observed by transmission electron microscopy (TEM).Results: TRY activity and melanin concentration were increased to 146.70 ± 10.28 % (p < 0.05) and 157.06 ± 6.37 % (p < 0.05), respectively, by 9.0 J/cm2 UVA irradiation for 8 min, compared to blank control without UV A and EGCG. EGCG inhibited the UV A induced increase in TRY activity and melanin level, and the optimum concentration of EGCG was 25 μg/mL. TRY activity and melanin concentration were decreased to 64.71 ± 4.41 (p < 0.05) and 86.24 ± 5.15 % (p < 0.05), respectively, compared to blank (control) which was neither treated by UVA nor by EGCG. TEM showed that UVA induced the formation of melanosomes while EGCG inhibited UVA-induced melanosome maturation.Conclusion: EGCG inhibits UVA-induced melanogenesis via suppression of TRY activity and melanosome maturation and is thus a potential alternative to melanogenesis inhibitor.Keywords: Green tea, Catechins, Melanin, Melanosome, Tyrosinase, Cell proliferatio

Stepwise pH control to promote synergy of chemical and biological processes for augmenting short-chain fatty acid production from anaerobic sludge fermentation

This is the author accepted manuscriptAlthough sludge-converted short-chain fatty acids (SCFAs) are promising feedstocks for biorefineries, it remains challenging to maximise SCFA production by enhancing synergies between chemical/biological hydrolysis and acidogenesis processes while employing a balanced composition of microbial communities to counteract methanogenesis. Herein, stepwise control of fermentation pH and chemical/microbiological composition analysis of fermented sludge were used to probe the underlying mechanisms of SCFA production. Fermentation at pH 11 during the first three days promoted both chemical and microbial hydrolysis of sludge proteins and provided a niche for Anaerobrancaceae sp. to transform soluble protein into SCFAs. When pH was decreased from 11 to 9, Acinetobacter, Proteiniborus, Proteiniclasticum, and other acetogens became predominant and stayed significantly more active than during first-stage fermentation at pH 11, which benefited the acidification of hydrolysed substrates. Further assays indicated that early-stage sludge fermentation at pH 11 decreased the total amount of methanogenic archaea and hence reduced the amount of SCFAs consumed for methane production. Thus, the use of stepwise pH control for sludge fermentation allowed one to establish process synergies, facilitate chemical and biological hydrolysis, inhibit methanogens, and promote the growth of acidifying bacterial communities, which resulted in efficient SCFA production from sludge.Royal Society Newton International Fellowshi

Cracking in asphalt materials

This chapter provides a comprehensive review of both laboratory characterization and modelling of bulk material fracture in asphalt mixtures. For the purpose of organization, this chapter is divided into a section on laboratory tests and a section on models. The laboratory characterization section is further subdivided on the basis of predominant loading conditions (monotonic vs. cyclic). The section on constitutive models is subdivided into two sections, the first one containing fracture mechanics based models for crack initiation and propagation that do not include material degradation due to cyclic loading conditions. The second section discusses phenomenological models that have been developed for crack growth through the use of dissipated energy and damage accumulation concepts. These latter models have the capability to simulate degradation of material capacity upon exceeding a threshold number of loading cycles.Peer ReviewedPostprint (author's final draft

MicroRNA-375 inhibits tumour growth and metastasis in oesophageal squamous cell carcinoma through repressing insulin-like growth factor 1 receptor

Background: To understand the involvement of micro- RNA (miRNA) in the development and progression of oesophageal squamous cell carcinoma (ESCC), miRNA profiles were compared between tumour and corresponding non-tumour tissues. Methods: miRCURY LNA array was used to generate miRNA expressing profile. Real-time quantitative PCR was applied to detectthe expression of miR-375 in ESCC samples and its correlation with insulin-like growth factor 1 receptor (IGF1R). Methylation-specific PCR was used to study the methylation status in the promoter region of miR-375. The tumour-suppressive effect of miR-375 was determined by both in-vitro and in-vivo assays. Results: The downregulation of miR-375 was frequently detected in primary ESCC, which was significantly correlated with advanced stage (p=0.003), distant metastasis (p<0.0001), poor overall survival (p=0.048) and disease-free survival (p=0.0006). Promoter methylation of miR-375 was detected in 26 of 45 (57.8%) ESCC specimens. Functional assays demonstrated that miR-375 could inhibit clonogenicity, cell motility, cell proliferation, tumour formation and metastasis in mice. Further study showed that miR-375 could interact with the 39-untranslated region of IGF1R and downregulate its expression. In clinical specimens, the expression of IGF1R was also negatively correlated with miR-375 expression (p=0.008). Conclusions: This study demonstrates that miR-375 has a strong tumour-suppressive effect through inhibiting the expression of IGF1R. The downregulation of miR-375, which is mainly caused by promoter methylation, is one of the molecular mechanisms involved in the development and progression of ESCC.published_or_final_versio

Podoplanin-positive cancer cells at the edge of esophageal squamous cell carcinomas are involved in invasion

Podoplanin (PDPN) is a well established lymphatic endothelial marker and has frequently been observed in cancer cells at the edge of cancer masses. Previous studies investigating the association between PDPN expression and patient prognosis have had contradictory results. In the present study, it was hypothesized that the different locations of PDPNpositive cells may explain these varying results. The present study aimed to focus on PDPN expression at the edge of esophageal cancer cell nests. In order to analyze the clinical significance of this PDPN expression, immunohistochemistry was performed using esophageal cancer tissue microarrays. PDPN expression at the edge of the cancer cell nest was found to be significantly associated with invasion (P<0.05) and poor prognosis (P<0.001) in patients with cancer. To further investigate the role of PDPN expression in cancer cells, the PDPN gene was cloned and transfected into esophageal squamous cell carcinoma (ESCC) cell lines. PDPN expression was also knocked down using small interfering RNA. PDPNpositive cancer cells were found to exhibit invasion characteristics. Thus, PDPN expression at the edge of a cancer cell nest may indicate invasion and represent a poor prognostic factor for ESCCs.published_or_final_versio

Refractive change following pseudophakic vitrectomy: a retrospective review

Background To assess the occurrence and magnitude of refractive change in pseudophakic eyes undergoing 20 gauge pars plana vitrectomy without scleral buckling and to investigate possible aetiological factors. Methods Retrospective case note review of 87 pseudophakic eyes undergoing 20 gauge pars plana vitrectomy for a variety of vitreo-retinal conditions over a three-year period. Anterior chamber depth (ACD) was measured before and after vitrectomy surgery in 32 eyes. Forty-three pseudophakic fellow eyes were used as controls. Results Eighty-seven eyes (84 patients) were included in the study. Mean spherical equivalent refraction prior to vitrectomy was -0.20 dioptres, which changed to a mean of -0.65 dioptres postoperatively (standard deviation of refractive change 0.59, range-2.13 to 0.75 dioptres) (p < 0.001). Sixty-one of the 87(70%) eyes experienced a myopic shift and 45(52%) eyes had a myopic shift of -0.5 dioptres or more. Mean fellow eye refraction was -0.19 dioptres preoperatively and -0.17 dioptres postoperatively (p = 0.14)(n = 37) Mean ACD preoperatively was 3.29 mm and postoperatively 3.27 mm (p = 0.53) (n = 32) and there was no significant change in ACD with tamponade use. Regression analysis revealed no statistically significant association between changes in anterior chamber depth, as well as a wide variety of other pre-, intra and postoperative factors examined, and the refractive change observed. Conclusion Significant refractive changes occur in some pseudophakic patients undergoing 20 g pars plana vitrectomy. The mean change observed was a small myopic shift but the range was large. The aetiology of the refractive change is uncertain

A space-time continuous finite element method for 2D viscoelastic wave equation

International audienceA widespread approach to software service analysis uses session types. Very different type theories for binary and multiparty protocols have been developed; establishing precise connections between them remains an open problem. We present the first formal relation between two existing theories of binary and multiparty session types: a binary system rooted in linear logic, and a multiparty system based on automata theory. Our results enable the analysis of multiparty protocols using a (much simpler) type theory for binary protocols, ensuring protocol fidelity and deadlock-freedom. As an application, we offer the first theory of multiparty session types with behavioral genericity. This theory is natural and powerful; its analysis techniques reuse results for binary session types

Immune adaptor ADAP in T cells regulates HIV-1 transcription and cell-cell viral spread via different co-receptors

Background: Immune cell adaptor protein ADAP (adhesion and degranulation-promoting adaptor protein) mediates aspects of T-cell adhesion and proliferation. Despite this, a connection between ADAP and infection by the HIV-1 (human immunodeficiency virus-1) has not been explored. Results: In this paper, we show for the first time that ADAP and its binding to SLP-76 (SH2 domain-containing leukocyte protein of 76 kDa) regulate HIV-1 infection via two distinct mechanisms and co-receptors. siRNA down-regulation of ADAP, or expression of a mutant that is defective in associating to its binding partner SLP-76 (termed M12), inhibited the propagation of HIV-1 in T-cell lines and primary human T-cells. In one step, ADAP and its binding to SLP-76 were needed for the activation of NF-κB and its transcription of the HIV-1 long terminal repeat (LTR) in cooperation with ligation of co-receptor CD28, but not LFA-1. In a second step, the ADAP-SLP-76 module cooperated with LFA-1 to regulate conjugate formation between T-cells and dendritic cells or other T-cells as well as the development of the virological synapse (VS) and viral spread between immune cells. Conclusions: These findings indicate that ADAP regulates two steps of HIV-1 infection cooperatively with two distinct receptors, and as such, serves as a new potential target in the blockade of HIV-1 infection