Echinacea purpurea-derived homogeneous polysaccharide exerts anti-tumor efficacy via facilitating M1 macrophage polarization

Echinacea purpurea modulates tumor progression,but the underlying mechanism is poorly defined.We isolated and purified a novel homogeneous polysaccharide from E.purpurea(EPPA),which was shown to be an arabinogalactan with a mean molecular mass(Mr)of 3.8×10^(4)Da and withα-(1→5)-L-Arabinan as the backbone and a-L-Araf-(1→,→6)-b-D-Galp-(1→,and →4)-α-D-GalpA-(1/as the side chains.Interestingly,oral administration of EPPA suppresses tumor progression in vivo and shapes the immune cell profile(e.g.,facilitating M1 macrophages)in tumor micro-environment by single-cell RNA sequencing(scRNA-seq)analysis.

Gut microbiota bridges dietary nutrients and host immunity

Dietary nutrients and the gut microbiota are increasingly recognized to cross-regulate and entrain each other,and thus affect host health and immune-mediated diseases.Here,we systematically review the current understanding linking dietary nutrients to gut microbiota-host immune interactions,emphasizing how this axis might influence host immunity in health and diseases.Of relevance,we highlight that the implications of gut microbiota-targeted dietary intervention could be harnessed in orchestrating a spectrum of immune-associated diseases.

Glutamine metabolism in Th17/Treg cell fate:applications in Th17 cell-associated diseases

Alteration in the Th17/Treg cell balance is implicated in various autoimmune diseases and these disease-associated pathologies.Increasing investigations have shown that glutamine metabolism regulates the differentiation of Th17 and Treg cells.Here we summarize the mechanisms by which glutamine metabolism regulates Th17/Treg cell fate.Some examples of a glutamine metabolism-dependent modulation of the development and progression of several Th17/Treg cell-associated diseases are provided afterward.This review will provide a comprehensive understanding of the importance of glutamine metabolism in the fate of Th17/Treg cell differentiation.

Melatonin shapes bacterial clearance function of porcine macrophages during enterotoxigenic Escherichia coli infection

Due to the immature gastrointestinal immune system,weaning piglets are highly susceptible to pathogens,e.g.,enterotoxigenic Escherichia coli(ETEC).Generally,pathogens activate the immune cells(e.g.,macrophages)and shape intracellular metabolism(including amino acid metabolism);nevertheless,the metabolic cues of tryptophan(especially melatonin pathway)in directing porcine macrophage function during ETEC infection remain unclear.Therefore,this study aimed to investigate the changes in the serotonin pathway of porcine macrophages during ETEC infection and the effect of melatonin on porcine macrophage functions.Porcine macrophages(3D4/21 cells)were infected with ETEC,and the change of serotonin pathway was analysed by reverse transcription PCR and metabolomic analysis.The effect of melatonin on porcine macrophage function was also studied with proteomic analysis.In order to investigate the effect of melatonin on bacterial clearance function of porcine macrophages during ETEC infection,methods such as bacterial counting,reverse transcription PCR and western blotting were used to detect the corresponding indicators.The results showed that ETEC infection blocked melatonin production in porcine macrophages(P<0.05)which is largely associated with the heat-stable enterotoxin b(STb)of ETEC(P<0.05).Interestingly,melatonin altered porcine macrophage functions,including bacteriostatic and bactericidal activities based on proteomic analysis.In addition,melatonin pretreatment significantly reduced extracellular lactate dehydrogenase(LDH)activity(P<0.05),indicating that melatonin also attenuated ETEC-triggered macrophage death.Moreover,melatonin pretreatment resulted in the decrease of viable ETEC in 3D4/21 cells(P<0.05),suggesting that melatonin enhances bacterial clearance of porcine macrophages.These results suggest that melatonin is particularly important in shaping porcine macrophage function during ETEC infection.

Melatonin inhibits Gram-negative pathogens by targeting citrate synthase

Bacterial infections caused by Gram-negative pathogens represent a growing burden for public health worldwide.Despite the urgent need for new antibiotics that effectively fight against pathogenic bacteria,very few compounds are currently under development or approved in the clinical setting.Repurposing compounds for other uses offers a productive strategy for the development of new antibiotics.Here we report that the multifaceted melatonin effectively improves survival rates of mice and decreases bacterial loads in the lung during infection.Mechanistically,melatonin specifically inhibits the activity of citrate synthase of Gram-negative pathogens through directly binding to the R300,D363,and H265 sites,particularly for the notorious Pasteurella multocida.These findings highlight that usage of melatonin is a feasible and alternative therapy to tackle the increasing threat of Gram-negative pathogen infections via disrupting metabolic flux of bacteria.