Targeting and exploitation of tumor-associated neutrophils to enhance immunotherapy and drug delivery for cancer treatment

Neutrophils,the most abundant leukocytes in human blood,are essential fighter immune cells against microbial infection.Based on the finding that neutrophils can either restrict or promote cancer progression,tumor-associated neutrophils(TAN)are classified into anti-tumor N1 and pro-tumor N2 subsets.One of the major mechanisms underlying the tumor-promoting function of N2-TANs is suppression of adaptive immune cells,in particular,cytotoxic T lymphocytes.Currently,no established methodologies are available that can unequivocally distinguish immunosuppressive TANs and granulocytic/polymorphonuclear myeloid-derived suppressor cells(G/PMN-MDSC).In view of the critical role of PMN-MDSCs in immune evasion and resistance to cancer immunotherapy,as established from data obtained with diverse cancer models,therapeutic strategies targeting these cells have been actively developed to enhance the efficacy of immunotherapy.Here,we have reviewed the available literature on strategies targeting PMN-MDSCs and summarized the findings into four categories:(1)depletion of existing PMN-MDSCs,(2)blockade of the development of PMNMDSCs,(3)blockade of PMN-MDSC recruitment,(4)inhibition of immunosuppressive function.Owing to their high mobility to inflamed organs and ability to trespass the blood-brain barrier,neutrophils are outstanding candidate carriers in nanoparticle-based therapies.Another attractive application of neutrophils in cancer therapy is the use of neutrophil membrane-derived nanovesicles as a surrogate of extracellular vesicles for more efficient and scalable drug delivery.In the second part of the review,we have highlighted recent advances in the field of neutrophil-based cancer drug delivery.Overall,we believe that neutrophil-based therapeutics are a rapidly growing area of cancer therapy with significant potential benefits.

Optimization of Acetic Acid Fermentation Process of Apple Cider Vinegar

This paper studied the fermentation rules of apple cider vinegar from fruit juice,to provide a theoretical guidance for the production of apple cider vinegar.Using Fuji apples as raw materials,the process parameters(fermentation temperature,fermentation time,stirring speed,and inoculation amount)of apple cider vinegar fermentation were optimized through single-factor experiments and response surface analysis.The results indicated that the fermentation temperature had no significant effect on the total acid content of apple cider vinegar fermentation,the fermentation time had an extremely significant effect on the total acid content of apple cider vinegar fermentation,and the stirring speed and inoculation amount had a significant effect on the total acid content of apple cider vinegar fermentation.Through process optimization,the optimal process parameters for apple cider vinegar fermentation are fermentation temperature of 33℃,fermentation time of 39 h,stirring speed of 1500 r/min,and acetic acid bacteria inoculation amount of 7%.Under such conditions,the total acid content of fermented apple cider vinegar is 62.22 g/L,very close to the predicted value of the model,indicating that the process parameters of acetic acid fermentation obtained by response surface methodology(RSM)optimization are reliable and can be used for actual production prediction.

Application of Transcriptomics in the Analysis of Community Structure of Food Fermented with Lactic Acid Bacteria

Revealing the structural characteristics,succession changes and functional genes of the microbial community in lactic acid bacteria-fermented food has been the focus of scientific research and industrial production for many years.In recent years,high-throughput sequencing technology has become an important tool for the research of lactic acid bacteria-fermented food microorganisms due to its advantages of high efficiency and being relatively cheap.In this paper,starting from the research on the genome,transcriptome and metabonomic levels of high-throughput sequencing technology,we reviewed the progress of transcriptomics in the study on microbial community structure,interaction,and functional gene mining of lactic acid bacteria-fermented food,and analyzed and discussed the main problems and development trends it faces,providing a certain reference for the scientific research and industrial production of fermented food in the future.

H19 recruited N^(6)-methyladenosine(m^(6)A)reader YTHDF1 to promote SCARB1 translation and facilitate angiogenesis in gastric cancer

Background:Angiogenesis is described as a complex process in which new microvessels sprout from endothelial cells of existing vasculature.This study aimed to determine whether long non-coding RNA(lncRNA)H19 induced the angiogenesis of gastric cancer(GC)and its possible mechanism.Methods:Gene expression level was determined by quantitative real-time polymerase chain reaction and western blotting.Cell counting kit-8,transwell,5-Ethynyl-2′-deoxyuridine(EdU),colony formation assay,and human umbilical vein endothelial cells(HUVECs)angiogenesis assay as well as Matrigel plug assay were conducted to study the proliferation,migration,and angiogenesis of GC in vitro and in vivo.The binding protein of H19 was found by RNA pull-down and RNA Immunoprecipitation(RIP).High-throughput sequencing was performed and next Gene Ontology(GO)as well as Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis was conducted to analyze the genes that are under H19 regulation.Methylated RIP(me-RIP)assay was used to investigate the sites and abundance among target mRNA.The transcription factor acted as upstream of H19 was determined through chromatin immunoprecipitation(ChIP)and luciferase assay.Results:In this study,we found that hypoxia-induced factor(HIF)-1a could bind to the promoter region of H19,leading to H19 overexpression.High expression of H19 was correlated with angiogenesis in GC,and H19 knocking down could inhibit cell proliferation,migration and angiogenesis.Mechanistically,the oncogenic role of H19 was achieved by binding with the N^(6)-methyladenosine(m^(6)A)reader YTH domain-containing family protein 1(YTHDF1),which could recognize the m^(6)A site on the 3′-untransated regions(3′-UTR)of scavenger receptor class B member 1(SCARB1)mRNA,resulting in over-translation of SCARB1 and thus promoting the proliferation,migration,and angiogenesis of GC cells.Conclusion:HIF-1a induced overexpression of H19 via binding with the promoter of H19,and H19 promoted GC cells proliferation,migration and angiogenesis through YTHDF1/SCARB1,which might be a beneficial target for antiangiogenic therapy for GC.

lncRNA TUG1 regulates Smac/DIABLO expression by competitively inhibiting miR-29b and modulates the apoptosis of lens epithelial cells in age-related cataracts

Background:As one of the early discovered long non-coding RNAs(lncRNA),taurine upregulation gene 1(TUG1)has been widely expressed in a variety of tumors.Moreover,it promotes cell proliferation,differentiation,apoptosis,and migration.However,our understanding of its importance in the pathogenesis of cataracts remains limited.This study aimed to explore the mechanism by which lncRNA TUG1 mediates lens epithelial cell apoptosis in age-related cataracts(ARC)by regulating the microRNAs(miR-29b)/second mitochondria-derived activator of caspases axis,and to identify more non-surgical strategies for cataract treatment.Methods:The messenger RNA expression levels of TUG1,miR-29b,and Smac were detected using quantitative real-time polymerase chain reaction in vivo and in vitro.The expression of the Smac protein was analyzed by Western blotting and immunofluorescence.Flow cytometry and cell counting kit-8 assays were used to detect the cell apoptosis and proliferation rates,respectively.The targeted regulatory relationship between lncRNA TUG1,miR-29b,and Smac was verified by viral vector construction,co-transfection,nuclear and cytoplasmic separation,luciferase reporter assays,and RNA immunoprecipitation.Results:TUG1 and Smac were expressed at high levels in ARC and HLE-B3 cells treated with 200μmol/L H_(2)O_(2),whereas miR-29b expression was decreased.In vitro cell experiments confirmed that down-regulation of TUG1 could inhibit the apoptosis of lens epithelial cells.Mechanistically,Smac expression was negatively regulated by miR-29b.TUG1 competitively inhibited miR-29b expression and caused greater release of Smac.In addition,miR-29b partially reversed the effects of TUG1 on human lens epithelial cell line cells.Conclusions:lncRNA TUG1 increases Smac expression and promotes apoptosis of lens epithelial cells in ARC by competitively inhibiting miR-29b.This mechanism is the cytological basis for ARC formation.Based on these results,the lncRNA TUG1/miR29b/Smac axis may be a new molecular pathway that regulates ARC development.

The Impact of COVID-19 on Tuberculosis Patients’Behavior of Seeking Medical Care——China,2020

Summary What is already known on this topic?The coronavirus disease 2019(COVID-19)pandemic has disrupted the tuberculosis(TB)service system.However,the impact on TB patients in China remains unknown.What is added by this report?This report firstly addressed the impact of COVID-19 on TB patients in China.About half of TB patients did not revisit the hospital due to personal reasons.The reasons for irregular medication and postponing or cancelling examination after full treatment course were different.

Effectiveness of the Integrated TB Surveillance System--China,2018-2019

What is already known about this topic?China’s national health information system provides important support and means for deepening the country’s medical and health reform,for improving relevant delivery services,for enhancing the level of scientific management of health,and for promoting the goal of basic medical and health services for everyone in China.What is added by this report?To further the construction of the national health information system,the National Center for Tuberculosis Control and Prevention of China CDC,started a pilot project for a new tuberculosis(TB)integrated health(iHealth)surveillance system,which was integrated with regional health information platforms.The goal was to explore automatic data exchange between hospitals and disease control facilities to reduce the workload of data-entry.What are the implications for public health practice?This pilot proved that data sharing and automatic exchanges between different information systems can be achieved through a unified surveillance dataset,which could provide a reference point for the construction of surveillance systems for other infectious diseases or for the entire public health information system.