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

A new multi-anticipative car-following model with consideration of the desired following distance

We propose in this paper an extension of the multi-anticipative optimal velocity car-following model to consider explicitly the desired following distance. The model on the following vehicle’s acceleration is formulated as a linear function of the optimal velocity and the desired distance, with reaction-time delay in elements. The linear stability condition of the model is derived. The results demonstrate that the stability of traffic flow is improved by introducing the desired following distance, increasing the time gap in the desired following distance or decreasing the reaction-time delay. The simulation results show that by taking into account the desired following distance as well as the optimal velocity, the multi-anticipative model allows longer reaction-time delay in achieving stable traffic flows

In situ production of titanium dioxide nanoparticles in molten salt phase for thermal energy storage and heat-transfer fluid applications

In this study, TiO2 nanoparticles (average particle size 16 nm) were successfully produced in molten salt phase and were showed to significantly enhance the specific heat capacity of a binary eutectic mixture of sodium and potassium nitrate (60/40) by 5.4 % at 390 °C and 7.5 % at 445 °C for 3.0 wt% of precursors used. The objective of this research was to develop a cost-effective alternate method of production which is potentially scalable, as current techniques utilized are not economically viable for large quantities. Enhancing the specific heat capacity of molten salt would promote more competitive pricing for electricity production by concentrating solar power plant. Here, a simple precursor (TiOSO4) was added to a binary eutectic mixture of potassium and sodium nitrate, heated to 450 °C, and cooled to witness the production of nanoparticles

Advances in understanding ischemic acute kidney injury

Acute kidney injury (AKI) is independently associated with increased morbidity and mortality. Ischemia is the leading cause of AKI, and short of supportive measures, no currently available therapy can effectively treat or prevent ischemic AKI. This paper discusses recent developments in the understanding of ischemic AKI pathophysiology, the emerging relationship between ischemic AKI and development of progressive chronic kidney disease, and promising novel therapies currently under investigation. On the basis of recent breakthroughs in understanding the pathophysiology of ischemic AKI, therapies that can treat or even prevent ischemic AKI may become a reality in the near future

Anti-Arthritic Effects of Magnolol in Human Interleukin 1β-Stimulated Fibroblast-Like Synoviocytes and in a Rat Arthritis Model

Fibroblast-like synoviocytes (FLS) play an important role in the pathologic processes of destructive arthritis by producing a number of catabolic cytokines and metalloproteinases (MMPs). The expression of these mediators is controlled at the transcriptional level. The purposes of this study were to evaluate the anti-arthritic effects of magnolol (5,5′-Diallyl-biphenyl-2,2′-diol), the major bioactive component of the bark of Magnolia officinalis, by examining its inhibitory effects on inflammatory mediator secretion and the NF-κB and AP-1 activation pathways and to investigate its therapeutic effects on the development of arthritis in a rat model. The in vitro anti-arthritic activity of magnolol was tested on interleukin (IL)-1β-stimulated FLS by measuring levels of IL-6, cyclooxygenase-2, prostaglandin E2, and matrix metalloproteinases (MMPs) by ELISA and RT-PCR. Further studies on how magnolol inhibits IL-1β-stimulated cytokine expression were performed using Western blots, reporter gene assay, electrophoretic mobility shift assay, and confocal microscope analysis. The in vivo anti-arthritic effects of magnolol were evaluated in a Mycobacterium butyricum-induced arthritis model in rats. Magnolol markedly inhibited IL-1β (10 ng/mL)-induced cytokine expression in a concentration-dependent manner (2.5–25 µg/mL). In clarifying the mechanisms involved, magnolol was found to inhibit the IL-1β-induced activation of the IKK/IκB/NF-κB and MAPKs pathways by suppressing the nuclear translocation and DNA binding activity of both transcription factors. In the animal model, magnolol (100 mg/kg) significantly inhibited paw swelling and reduced serum cytokine levels. Our results demonstrate that magnolol inhibits the development of arthritis, suggesting that it might provide a new therapeutic approach to inflammatory arthritis diseases

Expression and biological-clinical significance of hTR, hTERT and CKS2 in washing fluids of patients with bladder cancer

<p>Abstract</p> <p>Background</p> <p>at present, pathogenesis of bladder cancer (BC) has not been fully elucidated. Aim of this study is to investigate the role of human telomerase RNA (<it>hTR</it>), human telomerase reverse transcriptase (<it>hTERT</it>) and CDC28 protein kinase regulatory subunit 2 (<it>CKS2</it>) in bladder carcinogenesis and their possible clinical significance;</p> <p>Methods</p> <p>the transcript levels of <it>hTR</it>, <it>hTERT </it>and <it>CKS2 </it>were quantified by Real time reverse transcriptase chain reaction in exfoliated cells from bladder washings of 36 patients with BC and 58 controls. The statistical significance of differences between BC bearing patients and control groups, in the general as well as in the stratified analysis (superficial or invasive BC), was assessed by Student's t test. Non parametric Receiver Operating Characteristics analysis (ROC) was performed to ascertain the accuracy of study variables to discriminate between BC and controls. The clinical value of concomitant examination of <it>hTR</it>, <it>hTERT </it>and <it>CKS2 </it>was evaluated by logistic regression analysis;</p> <p>Results</p> <p>a significant decrease in <it>hTR </it>and a significant increase in <it>hTERT </it>or <it>CKS2 </it>gene expression were found between BC bearing patients and controls, as well as in the subgroups analysis. The area under the curve (AUC) indicated an average discrimination power for the three genes, both in the general and subgroups analysis, when singularly considered. The ability to significantly discriminate between superficial and invasive BC was observed only for <it>hTR </it>transcript levels. A combined model including <it>hTR </it>and <it>CKS2 </it>was the best one in BC diagnosis;</p> <p>Conclusions</p> <p>our results, obtained from a sample set particularly rich of exfoliated cells, provide further molecular evidence on the involvement of <it>hTR, hTERT </it>and <it>CKS2 </it>gene expression in BC carcinogenesis. In particular, while <it>hTERT </it>and <it>CKS2 </it>gene expression seems to have a major involvement in the early stages of the disease, <it>hTR </it>gene expression, seems to be more involved in progression. In addition, our findings suggest that the studied genes have a clinical role in discriminating between BC and controls in the general as well as in the stratified analysis, when singularly considered. A combined model improved over the single marker BC diagnosis.</p

Galectin-8 in IgA Nephritis: Decreased Binding of IgA by Galectin-8 Affinity Chromatography and Associated Increased Binding in Non-IgA Serum Glycoproteins

Background Immunoglobulin A nephritis (IgAN) is the most common primary glomerulonephritis worldwide. It is caused by accumulation of IgA1-containing immune complexes in the kidney resulting in renal failure, which is thought to be due to altered glycosylation of IgA with a decrease of 2-3-sialylated galactosides (NeuAc alpha 2-3Gal). less thanbrgreater than less thanbrgreater thanPurpose The purpose of this study was to analyze whether altered glycosylation of IgA would lead to an altered binding to galectin-8, an endogenous lectin with strong affinity for 2-3-sialylated galactosides. Galectins are a family of beta-galactoside-binding proteins; by binding various glycoproteins, they play important roles in the regulation of cellular functions in inflammation and immunity. Hence, an altered binding of IgA to galectin-8 could lead to pathologic immune functions, such as glomerulonephritis. less thanbrgreater than less thanbrgreater thanMethods Affinity chromatography of serum glycoproteins on the human sialogalactoside-binding lectin galectin-8N permitted quantitation of bound and unbound fractions, including IgA. less thanbrgreater than less thanbrgreater thanResults Analysis of similar to 100 IgA nephritis sera showed that the galectin-8N unbound fraction of IgA increased compared to similar to 100 controls, consistent with the known loss of galactosylation. A subgroup of similar to 15% of the IgAN patients had a ratio of galectin-8 bound/unbound IgA andlt;0.09, not found for any of the controls. Unexpectedly, the galectin-8N-binding fraction of serum glycoproteins other than IgA increased in the sera of IgAN patients but not in controls, suggesting a previously unrecognized change in this disease. less thanbrgreater than less thanbrgreater thanConclusion This is the first study that relates a galectin, an endogenous lectin family, to IgA nephritis and thus should stimulate new avenues of research into the pathophysiology of the disease.Funding Agencies|Swedish Research Council (Vetenskapsradet)|2008-3356|Swedish Foundation for Swedish Research|FFL4|Swedish Healthcare System (ALF)||Region Skane||</p

Metadherin Contributes to the Pathogenesis of Diffuse Large B-cell Lymphoma

BACKGROUND: Metadherin (MTDH) has been demonstrated as a potentially crucial mediator of various types of human malignancies. However, the expression and role of MTDH in diffuse large-B-cell lymphoma (DLBCL) have not been reported yet. This study aimed to illuminate the role of MTDH in the pathogenesis of DLBCL. METHODOLOGY/PRINCIPAL FINDINGS: A remarkable elevation of MTDH on mRNA level was detected in DLBCL tissues by quantitative polymerase chain reaction (PCR). Using Western-blot analysis we found that the expression of MTDH protein was significantly upregulated in DLBCL cell lines and DLBCL tissues compared with peripheral blood mononuclear cells (PBMCs) from healthy samples and tissues from patients of reactive hyperplasia of lymph node. The results showed high expression of MTDH in 23 of 30 (76.67%) DLBCL tissues by using immunohistochemical analysis and the over expression of MTDH was strongly correlated to the clinical staging of patients with DLBCL (P<0.05). Furthermore, the finding suggested that the increase of MTDH in DLBCL cells could distinctly enhance cell proliferation and inhibit cell apoptosis; meanwhile, inhibition of MTDH expression by specific siRNA clearly enhanced LY8 cell apoptosis. Upregulation of MTDH elevated the protein level of total β-catenin and translocation of β-catenin to the nucleus directly or indirectly. Knockdown of MTDH decreased the level of total, cytoplasmic β-catenin and reduced nuclear accumulation of β-catenin protein. This indicated that the function of MTDH on the development of DLBCL was mediated through regulation of Wnt/β-catenin signaling pathway. CONCLUSIONS/SIGNIFICANCE: Our results suggest that MTDH contributes to the pathogenesis of DLBCL mediated by activation of Wnt/β-catenin pathway. This novel study may contribute to further investigation on the useful biomarkers and potential therapeutic target in the DLBCL patients

Preventive Effects of Omega-3 and Omega-6 Fatty Acids on Peroxide Mediated Oxidative Stress Responses in Primary Human Trabecular Meshwork Cells

Pathologic processes in glaucoma include increased apoptosis, accumulation of extracellular material in the trabecular meshwork and optic nerve, condensations of the cytoskeleton and precocious cellular senescence. Oxidative stress was shown to generate these alterations in primary ocular cells. Fatty acids omega-3 and -6 are alleged to constitute a prophylaxis against these deleterious effects. Here, we tested actual preventive effects omega-3 and -6 against peroxide induced stress responses in primary human trabecular meshwork cells. Changes of mitochondrial activity, proliferation, heat shock proteins, extracellular matrix components, and inflammatory markers were evaluated. Alterations of the cytoskeleton were evaluated by phalloidin labeling. Here we report a repressive effect of omega-6 on metabolic activity and proliferation, which was not detected for omega-3. Both agents were able to prevent the anti-proliferative effect of H2O2, but only omega-3 prevented metabolic repression. Expression of heat shock protein 27 was unaltered by both fatty acids, whereas heat shock protein 90 was significantly induced by both. Omega-6 increased fibronectin and connective tissue growth factor synthesis, as well as the amount of secreted fibronectin. Omega-3, instead, induced plasminogen activator inhibitor 1 synthesis. H2O2 further increased fibronectin production in omega-6 supplemented cells, which was not the case in omega-3 treated cells. H2O2 stimulation of plasminogen activator inhibitor 1 and connective tissue growth factor was repressed by both fatty acids. Both fatty acids appeared to abolish H2O2 mediated stimulation of nuclear factor κB and IL-6, but not IL-1α and IL-8. H2O2 induced formation of cross-linked actin networks and stress fibers, which was reduced by preemptive application of omega-3. Omega-6, in contrast, had no protective effect on that, and even seemed to promote condensation. Based on the observed side effects of omega-6, omega-3 appears to be the more beneficial fatty acid in respect of prophylactic intake for prevention of a glaucomatous disease