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Lingjun Tong

Bio: Lingjun Tong is an academic researcher from Ocean University of China. The author has contributed to research in topics: Gut flora & Medicine. The author has an hindex of 4, co-authored 9 publications receiving 62 citations. Previous affiliations of Lingjun Tong include National University of Singapore.

Papers
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Journal ArticleDOI
TL;DR: In this paper, extracellular vesicles (EVs) have emerged as an attractive drug delivery system and the authors assess their pre-clinical applications, in the form of a systematic review.

70 citations

Journal ArticleDOI
TL;DR: In this paper, the effects of milk-derived extracellular vesicles (mEVs) as nanoparticles as novel drug vehicles due to their pivotal role in cell-cell communication were investigated.
Abstract: Scope Milk-derived extracellular vesicles (mEVs) as nanoparticles are being developed as novel drug vehicles due to their pivotal role in cell-cell communication. As an important bioactive component in milk, little is known about their effect on the gut microbiota and intestinal immunity. Therefore, the effects of mEVs on gut microbiota and intestinal immunity in mice are investigated. Methods and results First, a new method to obtain high-yield mEVs is developed. Afterward, the colonic contents from C57BL/6 mice fed different doses of mEVs (8 weeks) are collected and the microbial composition via 16S rRNA gene sequencing is analyzed. It is found that mEVs could alter the gut microbiota composition and modulate their metabolites-short-chain fatty acids (SCFAs). Furthermore, the effects of mEVs on intestinal immunity are evaluated. It is observed that the expression levels of Muc2, RegIIIγ, Myd88, GATA4 genes, and IgA, sIgA are increased in the intestine, which are significant for the integrity of the mucus layer. Conclusion These findings reveal that the genes with critical importance for intestinal barrier function and immune regulation are modified in mice by oral administration mEVs, which also result in the changes of the relative composition of gut microbiome and SCFAs.

63 citations

Journal ArticleDOI
TL;DR: In this paper, an effective protocol for the isolation of extracellular vesicles from milk (mEVs) and discovered that mEVs contained large amounts of immune-active proteins and modulated the gut immunity and microbiota in healthy mice.
Abstract: Rationale: Bovine milk constitutes an essential part of human diet, especially for children, due to its enrichment of various nutrients. We recently developed an effective protocol for the isolation of extracellular vesicles from milk (mEVs) and discovered that mEVs contained large amounts of immune-active proteins and modulated the gut immunity and microbiota in healthy mice. Here, we aimed to explore the therapeutic effects of mEVs on inflammatory bowel disease. Methods: MicroRNAs and protein content in mEVs were analyzed by RNA sequencing and proteomics, respectively, followed by functional annotation. Ulcerative colitis (UC) was induced by feeding mice with dextran sulfate sodium. Intestinal immune cell populations were phenotyped by flow cytometry, and the gut microbiota was analyzed via 16S rRNA sequencing. Results: We showed that abundant proteins and microRNAs in mEVs were involved in the regulation of immune and inflammatory pathways and that oral administration of mEVs prevented colon shortening, reduced intestinal epithelium disruption, inhibited infiltration of inflammatory cells and tissue fibrosis in a mouse UC model. Mechanistically, mEVs attenuated inflammatory response via inhibiting TLR4-NF-κB signaling pathway and NLRP3 inflammasome activation. Furthermore, mEVs were able to correct cytokine production disorder and restore the balance between T helper type 17 (Th17) cells and interleukin-10+Foxp3+ regulatory T (Treg) cells in the inflamed colon. The disturbed gut microbiota in UC was also partially recovered upon treatment with mEVs. The correlation between the gut microbiota and cytokines suggests that mEVs may modulate intestinal immunity via influencing the gut microbiota. Conclusions: These findings reveal that mEVs alleviate colitis by regulating intestinal immune homeostasis via inhibiting TLR4-NF-κB and NLRP3 signaling pathways, restoring Treg/Th17 cell balance, and reshaping the gut microbiota.

61 citations

Journal ArticleDOI
TL;DR: In this paper, the effect of extracellular vesicles released from L. rhamnosus GG (LGG-EVs) on dextran sulfate sodium (DSS)-induced colitis was explored.
Abstract: Ulcerative colitis (UC) is a relapsing and remitting inflammatory disease. Probiotics have a potential beneficial effect on the prevention of UC onset and relapse in clinical trials. Lactobacillus rhamnosus GG (L. rhamnosus GG) have shown clinical benefits on UC patients, however, the precise mechanisms are unknown. The aim of this study is to explore the effect of extracellular vesicles released from L. rhamnosus GG (LGG-EVs) on dextran sulfate sodium (DSS)-induced colitis and propose the underlying mechanism of LGG-EVs for protecting against colitis. The results showed that LGG-EVs could prevent colonic tissue damage and shortening of the colon (p < 0.01), and ameliorate intestinal inflammation by inhibiting TLR4-NF-κB-NLRP3 axis activation. Consistently, the pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-2) were suppressed effectively upon LGG-EVs treatment (p < 0.05). The 16S rRNA sequencing showed that LGG-EVs administration could reshape the gut microbiota in DSS-induced colitis mice, which further alters the metabolism pathways of gut microbiota. These findings propose a novel perspective of L. rhamnosus GG in attenuating inflammation mediated by extracellular vesicles and offer consideration for developing oral gavage of LGG-EVs for colitis therapies.

32 citations

Journal ArticleDOI
TL;DR: Lactis F1-7 and Lactobacillus vaginalis FN3 could regulate bile acid metabolism by downregulating the FXR gene and reduce the absorption of exogenous cholesterol by regulating NPC1L1.
Abstract: Probiotics effectively regulated lipid metabolism and improved hyperlipidemia. The purpose of this study was to further evaluate the functions of lipid-lowering strains in vivo and elucidate the mechanism. The hyperlipidemia model was constructed using a high fat diet, and four lipid-lowering strains were selected for intervention. In the four strains, the strains Lactobacillus vaginalis FN3 (FN3) and Bifidobacterium animalis subsp. Lactis F1-7 (F1-7) reduced TG, TC and LDL and increased HDL. These two strains decreased TC and TC in the liver of high fat diet fed mice, and they increased total bile acids (TBA) in feces. F1-7 and FN3 reduced the mRNA levels of Farnesoid X Receptor (FXR), recombinant Fibroblast Growth Factor 15 (FGF 15) and Niemann-Pick C1-Like 1 (NPC1L1), and up-regulated the Liver X Receptor (LXR) mRNA level. They decreased the protein expressions of FXR and NPC1L1. In addition, F1-7 up-regulated the protein expression of cholesterol 7-alpha hydroxylase (CYP7A1). In summary, Bifidobacterium animalis subsp. Lactis F1-7 and Lactobacillus vaginalis FN3 could regulate bile acid metabolism by downregulating the FXR gene and reduce the absorption of exogenous cholesterol by regulating NPC1L1. F1-7 could also participate in the FXR/FGF15 pathway to improve hyperlipidemia, which showed better effects than FN3.

20 citations


Cited by
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Journal ArticleDOI
TL;DR: In this article, the authors outline recent advances in artificial exosomes through nanobiotechnology and discuss their strengths, limitations, and future perspectives, and discuss the development of Artificial Exosomes holds great values for translational nanomedicine.
Abstract: Exosomes are lipid bilayer membrane vesicles and are emerging as competent nanocarriers for drug delivery. The clinical translation of exosomes faces many challenges such as massive production, standard isolation, drug loading, stability and quality control. In recent years, artificial exosomes are emerging based on nanobiotechnology to overcome the limitations of natural exosomes. Major types of artificial exosomes include 'nanovesicles (NVs)', 'exosome-mimetic (EM)' and 'hybrid exosomes (HEs)', which are obtained by top-down, bottom-up and biohybrid strategies, respectively. Artificial exosomes are powerful alternatives to natural exosomes for drug delivery. Here, we outline recent advances in artificial exosomes through nanobiotechnology and discuss their strengths, limitations and future perspectives. The development of artificial exosomes holds great values for translational nanomedicine.

91 citations

Journal ArticleDOI
TL;DR: The role of extracellular vesicle (EV) in the development and activation of B cells and T cells is summarized in this paper , which highlights key progress related to deciphering the roles of EVs in antimicrobial defence and in allergic, autoimmune and antitumour immune responses.
Abstract: The twenty-first century has witnessed major developments in the field of extracellular vesicle (EV) research, including significant steps towards defining standard criteria for the separation and detection of EVs. The recent recognition that EVs have the potential to function as biomarkers or as therapeutic tools has attracted even greater attention to their study. With this progress in mind, an updated comprehensive overview of the roles of EVs in the immune system is timely. This Review summarizes the roles of EVs in basic processes of innate and adaptive immunity, including inflammation, antigen presentation, and the development and activation of B cells and T cells. It also highlights key progress related to deciphering the roles of EVs in antimicrobial defence and in allergic, autoimmune and antitumour immune responses. It ends with a focus on the relevance of EVs to immunotherapy and vaccination, drawing attention to ongoing or recently completed clinical trials that aim to harness the therapeutic potential of EVs.

88 citations

Journal ArticleDOI
TL;DR: In this paper , the authors presented the development of lipid nanoparticles for COVID-19 vaccine delivery in 2020, which can deliver a drug for 12 hours after oral administration through an initial immediate dose followed by the remaining released gradually.

75 citations

Journal ArticleDOI
TL;DR: In this paper, extracellular vesicles (EVs) have emerged as an attractive drug delivery system and the authors assess their pre-clinical applications, in the form of a systematic review.

70 citations

Journal ArticleDOI
13 May 2020-Proteome
TL;DR: The role of milk-derived EVs in inter-organismal, cross-species communication and in drug delivery is discussed.
Abstract: Milk is considered as more than a source of nutrition for infants and is a vector involved in the transfer of bioactive compounds and cells. Milk contains abundant quantities of extracellular vesicles (EVs) that may originate from multiple cellular sources. These nanosized vesicles have been well characterized and are known to carry a diverse cargo of proteins, nucleic acids, lipids and other biomolecules. Milk-derived EVs have been demonstrated to survive harsh and degrading conditions in gut, taken up by various cell types, cross biological barriers and reach peripheral tissues. The cargo carried by these dietary EVs has been suggested to have a role in cell growth, development, immune modulation and regulation. Hence, there is considerable interest in understanding the role of milk-derived EVs in mediating inter-organismal and cross-species communication. Furthermore, various attributes such as it being a natural source, as well as its abundance, scalability, economic viability and lack of unwarranted immunologic reactions, has generated significant interest in deploying milk-derived EVs for clinical applications such as drug delivery and disease therapy. In this review, the role of milk-derived EVs in inter-organismal, cross-species communication and in drug delivery is discussed.

69 citations