Triple-Functional Probiotics with Intracellularly Synthesized Selenium Nanoparticles for Colitis Therapy by Regulating the Macrophage Phenotype and Modulating Gut Microbiota.

The dysregulated macrophage phenotype, as the main cause of colitis, not only enhanced oxidative stress to exacerbate inflammatory responses but was closely related with gut microbial dysbiosis. It was needed to simultaneously address the three issues for the effective treatment of colitis, but it was not satisfied. Here, we developed "three-birds-one-stone" probiotics, named Se@EcN-C/A, for colitis treatment.

Surface Mineralization of Engineered Bacterial Outer Membrane Vesicles to Enhance Tumor Photothermal/Immunotherapy.

Gram-negative bacteria can naturally produce nanosized spherical outer membrane vesicles (OMVs) with a lipid bilayer membrane, possessing immunostimulatory capabilities to be potentially applied in tumor therapy. However, the systemic toxicity induced by pathogen-associated molecular patterns (PAMPs) of OMVs is the main obstacle for their clinical translation. Herein, melanin-loaded OMVs were produced with a genetic engineering strategy and further coated with calcium phosphate (CaP) to reduce their toxicity to enhance tumor treatment effects.

Genetically engineered probiotics for an optical imaging-guided tumor photothermal therapy/immunotherapy.

Bacteria-based cancer therapy (BCT) has been extensively investigated because of the tumor targeting and antitumor immunity activating abilities of bacteria over traditional nanodrugs, but their potential systemic toxicity poses a challenge. Therefore, it is important to visualize the precise localization and real-time distribution of bacteria to guide the treatment. Herein, biogenetically engineered Nissle 1917 (EcN) were constructed to highly express tyrosinase to intracellularly generate cyanine 5-labeled melanin-like polymers (Cy5-Mel), thus endowing them with a bright fluorescence and an excellent photothermal performance upon NIR laser irradiation, thereby inducing the intense immunogenic death of tumor cells and release of tumor-associated antigens.

Engineered Extracellular Vesicles to Enhance Antigen Presentation for Boosting Light-Driven Tumor Immunotherapy.

Extracellular vesicles (EVs) have emerged as potential tools for tumor-target therapy accompanied with activating anticancer immune responses by serving as an integrated platform, but usually suffered from the limited cross presentation of tumor-associated antigen by dendritic cells (DCs). Here, a straightforward engineering strategy to construct heat shock proteins 70 (HSP70) highly expressed EVs incapsulated with Te nanoparticles (Te@EVs ) for tumor photothermal therapy triggering improved immunotherapy is proposed. Tumor cells are firstly used as bioreactors for intracellular synthesis of Te nanoparticles, and NIR irradiation is subsequently introduced to upregulate the expression of HSP70 to give engineered Te@EVs through exocytosis.

Bimetallic Ions Functionalized Metal-Organic-Framework Nanozyme for Tumor Microenvironment Regulating and Enhanced Photodynamic Therapy for Hypoxic Tumor.

Photodynamic therapy (PDT), as a light irradiation inducing reactive oxygen species (ROS) generation for cancer treatment, offers facile and promising solutions with respect to spatiotemporal control of ROS generation, and minimizes the systemic toxicity and side effects for highly precise tumor therapy. However, the PDT efficiency is often severely compromised by the complex tumor microenvironment (TME), such as the hypoxic condition and overexpressed antioxidants. Here, for the first time, a bimetallic ion-modified metal-organic framework nanozyme (Zr -MOF-Ru /Pt -Ce6@HA, ZMRPC@HA) is designed.

The role of imaging in targeted delivery of nanomedicine for cancer therapy.

Nanomedicines overcome the pharmacokinetic limitations of traditional drug formulations and have promising prospect in cancer treatment. However, nanomedicine delivery in vivo is still facing challenges from the complex physiological environment. For the purpose of effective tumor therapy, they should be designed to guarantee the five features principle, including long blood circulation, efficient tumor accumulation, deep matrix penetration, enhanced cell internalization and accurate drug release.

Bacterially Synthesized Tellurium Nanorods for Elimination of Advanced Malignant Tumor by Photothermal Immunotherapy.

Probiotic Escherichia coli Nissle 1917 (EcN) are employed as a bioreactor for intracellularly synthesizing tellurium nanorods (TeNRs) providing a biohybrid therapeutic platform (Te@EcN) for the elimination of advanced malignant tumor by photothermal immunotherapy. Te@EcN is found to possess superior photothermal property upon near-infrared irradiation, and can efficiently accumulate and retain in tumors, although EcN loses proliferation ability after the synthesis of TeNRs, thus inducing considerable immunogenic tumor cell death. Under co-stimulation by EcN acting as immunoadjuvants, maturation of dendritic cells and priming of cytotoxic T cells are largely promoted.

Inhibitor of Differentiation-2 Protein Ameliorates DSS-Induced Ulcerative Colitis by Inhibiting NF-κB Activation in Neutrophils.

The loss of inhibitor of differentiation-2 (ID2) could lead to the development of colitis in mice, supplementation with exogenous ID2 protein might be a potential strategy to ameliorate colitis. In this study, the effects of ID2 protein supplementation on Dextran sodium sulfate (DSS)-induced colitis were investigated. Firstly, we confirmed that the expression of ID2 was reduced in the colon tissues of DSS-induced colitis mice and patients with ulcerative colitis (UC).

Interplay between the Gut Microbiome and Metabolism in Ulcerative Colitis Mice Treated with the Dietary Ingredient Phloretin.

A growing number of healthy dietary ingredients in fruits and vegetables have been shown to exhibit diverse biological activities. Phloretin, a dihydrochalcone flavonoid that is abundant in apples and pears, has anti-inflammatory effects on ulcerative colitis (UC) mice. The gut microbiota and metabolism are closely related to each other due to the existence of the food-gut axis in the human colon.

Albumin-Templated BiSe-MnO Nanocomposites with Promoted Catalase-Like Activity for Enhanced Radiotherapy of Cancer.

Novel and effective radiosensitizers that can enhance radiosensitivity of tumor tissues and increase the local radiation dose are highly desirable. In this work, templated by bovine serum albumin (BSA), BiSe-MnO nanocomposites (BiSe-MnO@BSA) were fabricated via biomineralization, while BiSe nanodots act as radiosensitizers to increase the local radiation dosage because of their strong X-ray attenuation ability, and MnO with catalase-like activity can increase the oxygen concentration in tumors by triggering the decomposition of tumor endogenous HO so as to improve the hypoxia-associated radioresistance of tumors. Owing to the interaction of the two components in the interface, BiSe-MnO@BSA showed promoted catalytic activity compared to MnO@BSA, favoring tumor radiotherapy (RT) sensitization.

Influence of the densities and nutritional components of bacterial colonies on the culture-enriched gut bacterial community structure.

Isolating relevant microorganisms is still a substantial challenge that limits the use of bacteria in the maintenance of human health. To confirm which media and which bacterial colony densities can enrich certain kinds of bacteria, we selected eight common media and used them to enrich the gut microorganisms on agar plates. Then, we calculated the numbers of bacterial colonies and collected the bacterial culture mixtures from each kind of medium.

The responses of the gut microbiota to MBL deficiency.

Mannose-binding lectin (MBL) deficiency is a common innate immune system deficiency, and is associated with exacerbations and increased colonization of some pathogens. However, the response of the gut microbiota, a pivotal factor in host health, to MBL deficiency is not clear. In this study, MBL and wild-type (WT) mice were generated by backcrossing from MBL-A and MBL-C knockout (KO) mice, and fecal samples were collected at different ages (4th, 8th, 12th, 19th and 27th weeks).

Saikosaponin-d ameliorates dextran sulfate sodium-induced colitis by suppressing NF-κB activation and modulating the gut microbiota in mice.

Saikosaponin-d (SSd), extracts from Bupleurum falcatum L, exhibits anti-inflammatory and anti-infectious activities. However, the effect of SSd on intestinal inflammation has not been investigated. The aim of this study was to evaluate the effect of SSd on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice, and to elucidate the underlying mechanisms.

Phloretin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice by regulating the gut microbiota.

Phloretin, extracted from the pericarp and velamen of apples or pears, is a dihydrochalcone flavonoid with anti-bacterial and anti-inflammatory activities. It has been reported that phloretin has anti-inflammatory effects in ulcerative colitis (UC) mice. However, the role of the gut microbiota in the phloretin anti-UC process remains unclear.

The Differences between Luminal Microbiota and Mucosal Microbiota in Mice.

The differences between luminal microbiota (LM) and mucosal microbiota (MAM) were little known, especially in duodenum. In this study, LM and MAM in colon and duodenum of mice were investigated through 16S rRNA high-throughput sequencing. The lowest bacterial diversity and evenness were observed in duodenal LM (D_LM), followed by duodenal MAM (D_MAM).

Chitooligosaccharides Prevents the Development of Colitis-Associated Colorectal Cancer by Modulating the Intestinal Microbiota and Mycobiota.

Gut microbes play a crucial role in the development of colorectal cancer. Chitooligosaccharides (COS), are oligomer that are depolymerized from chitosan and possess a wide range of biological activities. In this study, the effects of COS on colorectal cancer (CRC) development were evaluated using azoxymethane and dextran sulfate sodium (AOM/DSS) induced mouse model of CRC (CACM).