Plant-nanoparticles enhance anti-PD-L1 efficacy by shaping human commensal microbiota metabolites.

Diet has emerged as a key impact factor for gut microbiota function. However, the complexity of dietary components makes it difficult to predict specific outcomes. Here we investigate the impact of plant-derived nanoparticles (PNP) on gut microbiota and metabolites in context of cancer immunotherapy with the humanized gnotobiotic mouse model.

Tryptophan As a New Member of RNA-Induced Silencing Complexes Prevents Colon Cancer Liver Metastasis.

Essential amino acids (EAA) and microRNAs (miRs) control biological activity of a cell. Whether EAA regulates the activity of miR has never been demonstrated. Here, as proof-of-concept, a tryptophan (Trp, an EAA) complex containing Argonaute 2 (Ago2) and miRs including miR-193a (Trp/Ago2/miR-193a) is identified.

Outer Membrane Vesicles Released from Garlic Exosome-like Nanoparticles (GaELNs) Train Gut Bacteria that Reverses Type 2 Diabetes via the Gut-Brain Axis.

Gut microbiota function has numerous effects on humans and the diet humans consume has emerged as a pivotal determinant of gut microbiota function. Here, a new concept that gut microbiota can be trained by diet-derived exosome-like nanoparticles (ELNs) to release healthy outer membrane vesicles (OMVs) is introduced. Specifically, OMVs released from garlic ELN (GaELNs) trained human gut Akkermansia muciniphila (A.

An extracellular vesicular mutant KRAS-associated protein complex promotes lung inflammation and tumor growth.

Extracellular vesicles (EVs) contain more than 100 proteins. Whether there are EVs proteins that act as an 'organiser' of protein networks to generate a new or different biological effect from that identified in EV-producing cells has never been demonstrated. Here, as a proof-of-concept, we demonstrate that EV-G12D-mutant KRAS serves as a leader that forms a protein complex and promotes lung inflammation and tumour growth via the Fn1/IL-17A/FGF21 axis.

Gut bacterial isoamylamine promotes age-related cognitive dysfunction by promoting microglial cell death.

The intestinal microbiome releases a plethora of small molecules. Here, we show that the Ruminococcaceae metabolite isoamylamine (IAA) is enriched in aged mice and elderly people, whereas Ruminococcaceae phages, belonging to the Myoviridae family, are reduced. Young mice orally administered IAA show cognitive decline, whereas Myoviridae phage administration reduces IAA levels.

Ginger nanoparticles mediated induction of Foxa2 prevents high-fat diet-induced insulin resistance.

The obesity epidemic has expanded globally, due in large part to the increased consumption of high-fat diets (HFD), and has increased the risk of major chronic diseases, including type 2 diabetes. Diet manipulation is the foundation of prevention and treatment of obesity and diabetes. The molecular mechanisms that mediate the diet-based prevention of insulin resistance, however, remain to be identified.

Garlic exosome-like nanoparticles reverse high-fat diet induced obesity via the gut/brain axis.

Obesity is becoming a global epidemic and reversing the pathological processes underlying obesity and metabolic co-morbidities is challenging. Obesity induced chronic inflammation including brain inflammation is a hallmark of obesity via the gut-brain axis. The objective of this study was to develop garlic exosome-like nanoparticles (GaELNs) that inhibit systemic as well as brain inflammatory activity and reverse a HFD induced obesity in mice.

Exosome-like nanoparticles from Mulberry bark prevent DSS-induced colitis via the AhR/COPS8 pathway.

Bark protects the tree against environmental insults. Here, we analyzed whether this defensive strategy could be utilized to broadly enhance protection against colitis. As a proof of concept, we show that exosome-like nanoparticles (MBELNs) derived from edible mulberry bark confer protection against colitis in a mouse model by promoting heat shock protein family A (Hsp70) member 8 (HSPA8)-mediated activation of the AhR signaling pathway.

Various potentially toxic element tolerances in different rice genotypes correlate with distinct physiological responses and alterations in DNA methylation.

Potentially toxic elements (PTEs) are harmful to plant growth and reduce crop productivity. In this work, we studied three rice genotypes (T-35, RZ-1, and RZ-2) to quantify the diverse PTE effects and tolerances by examining morphology, physiology, and DNA methylation patterns. Morphological results showed that T-35 exhibits the highest tolerance to all studied PTE stressors (Cu, Cd, Cr).

Restoring Oat Nanoparticles Mediated Brain Memory Function of Mice Fed Alcohol by Sorting Inflammatory Dectin-1 Complex Into Microglial Exosomes.

Microglia modulate pro-inflammatory and neurotoxic activities. Edible plant-derived factors improve brain function. Current knowledge of the molecular interactions between edible plant-derived factors and the microglial cell is limited.

Lemon exosome-like nanoparticles enhance stress survival of gut bacteria by RNase P-mediated specific tRNA decay.

Diet and bile play critical roles in shaping gut microbiota, but the molecular mechanism underlying interplay with intestinal microbiota is unclear. Here, we showed that lemon-derived exosome-like nanoparticles (LELNs) enhance lactobacilli toleration to bile. To decipher the mechanism, we used GG (LGG) as proof of concept to show that LELNs enhance LGG bile resistance via limiting production of Msp1 and Msp3, resulting in decrease of bile accessibility to cell membrane.

Plant-derived exosomal microRNAs inhibit lung inflammation induced by exosomes SARS-CoV-2 Nsp12.

Lung inflammation is a hallmark of coronavirus disease 2019 (COVID-19). In this study, we show that mice develop inflamed lung tissue after being administered exosomes released from the lung epithelial cells exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Nsp12 and Nsp13 (exosomes). Mechanistically, we show that exosomes are taken up by lung macrophages, leading to activation of nuclear factor κB (NF-κB) and the subsequent induction of an array of inflammatory cytokines.

miR-375 prevents high-fat diet-induced insulin resistance and obesity by targeting the aryl hydrocarbon receptor and bacterial tryptophanase () gene.

Diet manipulation is the basis for prevention of obesity and diabetes. The molecular mechanisms that mediate the diet-based prevention of insulin resistance are not well understood. Here, as proof-of-concept, ginger-derived nanoparticles (GDNP) were used for studying molecular mechanisms underlying GDNP mediated prevention of high-fat diet induced insulin resistance.

High-fat diet-induced upregulation of exosomal phosphatidylcholine contributes to insulin resistance.

High-fat diet (HFD) decreases insulin sensitivity. How high-fat diet causes insulin resistance is largely unknown. Here, we show that lean mice become insulin resistant after being administered exosomes isolated from the feces of obese mice fed a HFD or from patients with type II diabetes.

Lemon Exosome-like Nanoparticles-Manipulated Probiotics Protect Mice from Infection.

is the leading cause of antibiotic-associated colitis. Here, we report that lemon exosome-like nanoparticles (LELNs) manipulated probiotics to inhibit infection (CDI). LELN-manipulated GG (LGG) and ST-21 (STH) (LELN-LS) decrease CDI mortality via an LELN-mediated increase in bile resistance and gut survivability.

Plant-Derived Exosomal Nanoparticles Inhibit Pathogenicity of Porphyromonas gingivalis.

Plant exosomes protect plants against infection; however, whether edible plant exosomes can protect mammalian hosts against infection is not known. In this study, we show that ginger exosome-like nanoparticles (GELNs) are selectively taken up by the periodontal pathogen Porphyromonas gingivalis in a GELN phosphatidic acid (PA) dependent manner via interactions with hemin-binding protein 35 (HBP35) on the surface of P. gingivalis.

Plant-Derived Exosomal MicroRNAs Shape the Gut Microbiota.

The gut microbiota can be altered by dietary interventions to prevent and treat various diseases. However, the mechanisms by which food products modulate commensals remain largely unknown. We demonstrate that plant-derived exosome-like nanoparticles (ELNs) are taken up by the gut microbiota and contain RNAs that alter microbiome composition and host physiology.

Blood exosomes regulate the tissue distribution of grapefruit-derived nanovector via CD36 and IGFR1 pathways.

Tumor-specific delivery of therapeutics is challenging. One of the major hurdles for successfully delivering targeted agents by nanovectors is the filtering role of the liver in rapidly sequestering nanovectors from the circulation. Exosomes, a type of endogenous nanoparticle, circulate continuously in the peripheral blood and play a role in intercellular communication.

Broccoli-Derived Nanoparticle Inhibits Mouse Colitis by Activating Dendritic Cell AMP-Activated Protein Kinase.

The intestinal immune system is continuously exposed to massive amounts of nanoparticles derived from food. Whether nanoparticles from plants we eat daily have a role in maintaining intestinal immune homeostasis is poorly defined. Here, we present evidence supporting our hypothesis that edible nanoparticles regulate intestinal immune homeostasis by targeting dendritic cells (DCs).

MVP-mediated exosomal sorting of miR-193a promotes colon cancer progression.

Exosomes are emerging mediators of intercellular communication; whether the release of exosomes has an effect on the exosome donor cells in addition to the recipient cells has not been investigated to any extent. Here, we examine different exosomal miRNA expression profiles in primary mouse colon tumour, liver metastasis of colon cancer and naive colon tissues. In more advanced disease, higher levels of tumour suppressor miRNAs are encapsulated in the exosomes.

Isolation, identification, and characterization of novel nanovesicles.

Extracellular microvesicles (EVs) have been recognized for many potential clinical applications including biomarkers for disease diagnosis. In this study, we identified a major population of EVs by simply screening fluid samples with a nanosizer. Unlike other EVs, this extracellular nanovesicle (named HG-NV, HG-NV stands for HomoGenous nanovesicle as well as for Huang-Ge- nanovesicle) can be detected with a nanosizer with minimal in vitro manipulation and are much more homogenous in size (8-12 nm) than other EVs.