Inhibitory effect of Cyrtomium falcatum on melanogenesis in α-MSH-stimulated B16F10 murine melanoma cells

Objective:To explore the anti-melanogenic potential of Cyrtomium falcatum.Methods:The effects of Cyrtomium falcatum crude extract and its solvent fractions on tyrosinase activity,melanin content,and the expressions of melanogenesis-related genes and proteins were analyzed inα-melanocyte-stimulating hormone(α-MSH)-stimulated B16F10 cells.Results:α-MSH treatment significantly increased tyrosinase activity,and extracellular and intracellular melanin content,as well as the expression levels of tyrosinase,microphthalmia-associated transcription factor(MITF),tyrosinase-related protein(TRP)-1,and TRP-2 in B16F10 cells.Treatment with Cyrtomium falcatum crude extract and its solvent fractions reduced tyrosinase activity and extracellular and intracellular melanin content and downregulated the expression levels of tyrosinase,MITF,TRP-1,and TRP-2 in a dose-dependent manner.Conclusions:Cyrtomium falcatum has potential anti-melanogenesis effects and can be used as a potential source material in cosmeceutical industry for the research and development of novel lead molecules with whitening properties.

Oxidative stress-initiated one-carbon metabolism drives the generation of interleukin-10-producing B cells to resolve pneumonia

The metabolic reprogramming underlying the generation of regulatory B cells during infectious diseases remains unknown.Using a Pseudomonas aeruginosa-induced pneumonia model,we reported that IL-10-producing B cells(IL-10+B cells)play a key role in spontaneously resolving infection-mediated inflammation.Accumulated cytosolic reactive oxygen species(ROS)during inflammation were shown to drive IL-10+B-cell generation by remodeling one-carbon metabolism.Depletion of the enzyme serine hydroxymethyltransferase 1(Shmt1)led to inadequate one-carbon metabolism and decreased IL-10+B-cell production.Furthermore,increased one-carbon flux elevated the levels of the methyl donor S-adenosylmethionine(SAM),altering histone H3 lysine 4 methylation(H3K4me)at the Il10 gene to promote chromatin accessibility and upregulate Il10 expression in B cells.Therefore,the one-carbon metabolism-associated compound ethacrynic acid(EA)was screened and found to potentially treat infectious pneumonia by boosting IL-10+B-cell generation.Overall,these findings reveal that ROS serve as modulators to resolve inflammation by reprogramming one-carbon metabolism pathways in B cells.

Detraining after tumor-bearing accelerates tumor growth while continuous training decreases tumor growth in mice

Objective:Previous studies have shown that exercise suppresses tumor growth.However,the effects of exercise with different intensities and exercise detraining after tumor-bearing on tumor progression remain unclear.The purpose of this study was to investigate the effects of continuous and disrupted free and exhausted swimming training after tumor-bearing on tumor progression in melanoma B16-F10-bearing C57BL/6 mice.Methods:C57BL/6 mice were subjected to free or exhausted swimming exercise training for 4 weeks prior to the injection of melanoma B16-F10 cells.Subsequently,the B16-F10-bearing mice were maintained with training consisting of free or exhausted swimming or without exercise for 2 weeks during the tumor challenge.Results:The tumor weight was increased by 42%and 109%in mice with 4-week exhausted swimming prior to B16-F10 tumor cells inoculation followed by 2-week training cessation compared with the tumor-bearing control(P<.05)and continuous training groups(P<.01).Tumor weights in groups with exercise detraining after tumor cell inoculation tended to be increased,while the proliferation of splenic T lymphocytes tended to be decreased compared with the group that maintained exercise intensity.After 6-weeks continuous free or exhausted swimming training,the tumor weight of mice was decreased and the proliferation of splenic T lymphocytes was increased compared with the tumor-bearing control group.The frequency of natural killer cells in tumors was increased in all exercise training groups of mice.Conclusions:These results suggest that maintaining exercise intensity after tumor-bearing slows tumor growth in mice,possibly because of the enhanced proliferative activity of splenic lymphocytes rather than natural killer cell infiltration.However,detraining after tumor-bearing might accelerate tumor progression because of the reduced proliferation of splenic T lymphocytes.

Synthesis of poly(amidoamine)-poly(ethyleneglycol)-poly(amidoamine) and preparation of its hydrogel solution containing doxorubicin

Many pH-and temperature-responsive polymers have been designed for preparing hydrogel.In the present study,in order to decrease the pH sensitivity of reported poly(amidoamine)-poly(ethyleneglycol)-poly(amidoamine)(PAA1580-PEG4600-PAA1580),we designed and synthesized poly(amidoamine)-poly(ethyleneglycol)-poly(amidoamine)(PAA-PEG-PAA)with shorter length of PAA chain by decreasing reaction temperature for preparing PAA-PEG-PAA hydrogel solution containing doxorubicin(DOX).The PAA-PEG-PAA was synthesized via the Michael-addition polymerization.The characteristic of PAA-PEG-PAA was evaluated.The PAA-PEG-PAA hydrogel solution was prepared and investigated.DOX-loaded PAA-PEG-PAA hydrogel solution was prepared,and its in vitro DOX release and in vitro anti-tumor activity were evaluated.Our results indicated that the viscosity of PAA-PEG-PAA hydrogel solution was concentration-and temperature-dependent.The sol-gel transition temperature of PAA-PEG-PAA hydrogel solution(12%,w/w)ranged from 35 to 29℃,and its pH ranged from 6.0 to 7.4.The released DOX from DOX-loaded PAA-PEG-PAA hydrogel showed sustained release characteristics.The in vitro anti-tumor activity of DOX-loaded PAA-PEG-PAA hydrogel was confirmed in B16 F10 cell line.Considering the acidic tumor microenvironment,this DOX-loaded PAA-PEG-PAA hydrogel solution would be easy in situ administration for intra-tumor injection or para-tumor injection forming hydrogel at body temperature.We suggested that this DOX-loaded PAA-PEG-PAAhydrogel solution,if containing photothermal conversion agents,would have a potential further use for photothermal therapy.