Mesenchymal Stem Cell‐Derived Extracellular Vesicles with High PD‐L1 Expression for Autoimmune Diseases Treatment

Advanced Materials, Год журнала: 2021, Номер 34(1)

Опубликована: Окт. 8, 2021

Autoimmune diseases are the third most common disease influencing quality of life many patients. Here, a programmed cell death-ligand 1 + (PD-L1) mesenchymal stem (MSC) derived extracellular vesicles (MSC-sEVs-PD-L1) using lentivirus-mediated gene transfection technology is developed for reconfiguration local immune microenvironment affected tissue in autoimmune diseases. MSC-sEVs-PD-L1 exhibits an impressive ability to regulate various activated cells immunosuppressed state vitro. More importantly, dextran sulfate sodium-induced ulcerative colitis (UC) and imiquimod-induced psoriasis mouse models, significantly high accumulation observed inflamed tissues compared PD-L1+ MSCs. Therapeutic efficiency both UC models demonstrated reshape inflammatory ecosystem context. A as natural delivery platform treatment with clinical potential.

Язык: Английский

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Extracellular vesicles of Fusobacterium nucleatum compromise intestinal barrier through targeting RIPK1-mediated cell death pathway

Gut Microbes, Год журнала: 2021, Номер 13(1)

Опубликована: Янв. 1, 2021

Microbial factors that mediate microbes-host interaction in ulcerative colitis (UC), a chronic disease seriously affecting human health, are not fully known. The emerging oncobacterium Fusobacterium nucleatum (Fn) secretes extracellular vesicles carrying several types of harmful molecules the intestine which can alter interaction, especially epithelial homeostasis UC. However, mechanism is yet clear. Previously, we isolated EVs by ultracentrifugation Fn culture media and characterized them as potent inducer pro-inflammatory cytokines. Here, examined detail. We found macrophage/Caco-2 co-cultures, FnEVs significantly promoted barrier loss oxidative stress damage, related to necroptosis caused activation receptor-interacting protein kinase 1 (RIPK1) 3 (RIPK3). Furthermore, migration RIPK1 RIPK3 into necrosome Caco2 cells. Notably, these effects were reversed TNF-α neutralizing antibody or Necrostatin-1 (Nec-1), inhibitor. This suggested FADD-RIPK1-caspase-3 signaling involved process. Moreover, observed verified murine model treated with adoptive transfer FnEVs-trained macrophages. In conclusion, propose RIPK1-mediated cell death promotes FnEVs-induced gut disruption UC findings be used basis further investigate this disease.

Язык: Английский

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Engineered Bacteriophage Therapeutics: Rationale, Challenges and Future

BioDrugs, Год журнала: 2021, Номер 35(3), С. 255 - 280

Опубликована: Апрель 21, 2021

The current problems with increasing bacterial resistance to antibacterial therapies, resulting in a growing frequency of incurable infections, necessitates the acceleration studies on antibacterials new generation that could offer an alternative antibiotics or support their action. Bacteriophages (phages) can kill antibiotic-sensitive as well antibiotic-resistant bacteria, and thus are major subject such studies. Their efficacy curing infections has been demonstrated vivo experiments clinic. Unlike antibiotics, phages have narrow range specificity, which makes them safe for commensal microbiota. However, targeting even only most clinically relevant strains pathogenic bacteria requires large collections characterized phages, whose specificity would cover all strains. environment is rich source diverse but due complex relationships safety concerns, some naturally occurring be considered therapeutic applications. Still, number diversity make detailed characterization potentially promising virtually impossible. Moreover, no single phage combines features required ideal agent. Additionally, rapid acquisition by may already approved therapy ineffective turn search environmental better into endless race. An strategy acquiring desired properties short time minimal cost regarding acquisition, characterization, approval based targeted genome modifications isolates known properties. first example demonstrating potential this diseases resistant traditional recent successful treatment progressing disseminated Mycobacterium abscessus infection teenage patient use engineered phage. In review, we briefly present methods genetic engineering, highlighting advantages disadvantages, provide examples genetically modified host range, improved activity, proven efficacy. We also summarize novel uses not killing situ modification human microbiota attenuate symptoms certain metabolic, immune, mental disorders.

Язык: Английский

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Breaking the barriers: the role of gut homeostasis in Metabolic-Associated Steatotic Liver Disease (MASLD)

Gut Microbes, Год журнала: 2024, Номер 16(1)

Опубликована: Март 21, 2024

Obesity, insulin resistance (IR), and the gut microbiome intricately interplay in Metabolic-associated Steatotic Liver Disease (MASLD), previously known as Non-Alcoholic Fatty (NAFLD), a growing health concern. The complex progression of MASLD extends beyond liver, driven by "gut-liver axis," where diet, genetics, gut-liver interactions influence disease development. pathophysiology involves excessive liver fat accumulation, hepatocyte dysfunction, inflammation, fibrosis, with subsequent risk hepatocellular carcinoma (HCC). gut, tripartite barrier, mechanical, immune, microbial components, engages constant communication liver. Recent evidence links dysbiosis disrupted barriers to systemic inflammation progression. Toll-like receptors (TLRs) mediate immunological crosstalk between recognizing structures triggering immune responses. "multiple hit model" development factors like resistance, dysbiosis, genetics/environmental elements disrupting axis, leading impaired intestinal barrier function increased permeability. Clinical management strategies encompass dietary interventions, physical exercise, pharmacotherapy targeting bile acid (BA) metabolism, modulation approaches through prebiotics, probiotics, symbiotics, fecal microbiota transplantation (FMT). This review underscores microbiome, their impact on therapeutic prospects.

Язык: Английский

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Emerging role of the host microbiome in neuropsychiatric disorders: overview and future directions

Molecular Psychiatry, Год журнала: 2023, Номер 28(9), С. 3625 - 3637

Опубликована: Сен. 1, 2023

Abstract The human body harbors a diverse ecosystem of microorganisms, including bacteria, viruses, and fungi, collectively known as the microbiota. Current research is increasingly focusing on potential association between microbiota various neuropsychiatric disorders. resides in parts body, such oral cavity, nasal passages, lungs, gut, skin, bladder, vagina. gut gastrointestinal tract has received particular attention due to its high abundance role psychiatric neurodegenerative However, presents other tissues, though less abundant, also plays crucial immune system homeostasis, thus influencing development progression For example, imbalance associated periodontitis might increase risk for Additionally, studies using postmortem brain samples have detected widespread presence bacteria brains patients with Alzheimer’s disease. This article provides an overview emerging host disorders discusses future directions, underlying biological mechanisms, reliable biomarkers microbiota, microbiota-targeted interventions, this field.

Язык: Английский

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A major mechanism for immunomodulation: Dietary fibres and acid metabolites

Seminars in Immunology, Год журнала: 2023, Номер 66, С. 101737 - 101737

Опубликована: Фев. 27, 2023

Язык: Английский

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Gut-liver axis calibrates intestinal stem cell fitness

Cell, Год журнала: 2024, Номер 187(4), С. 914 - 930.e20

Опубликована: Янв. 26, 2024

Язык: Английский

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The immunology of systemic lupus erythematosus

Nature Immunology, Год журнала: 2024, Номер 25(8), С. 1332 - 1343

Опубликована: Июль 15, 2024

Язык: Английский

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Gut Microbiota and Autoimmune Diseases: Mechanisms, Treatment, Challenges, and Future Recommendations

Current Clinical Microbiology Reports, Год журнала: 2024, Номер 11(1), С. 18 - 33

Опубликована: Янв. 16, 2024

Abstract Purpose of Review This review provides an overview the role dysbiosis (imbalanced gut microbiota) in maintenance host homeostasis and immune function summarizes recent evidence connecting microbiota to development autoimmune diseases (ADs) (such as rheumatoid arthritis, type 1 diabetes, systemic lupus erythematosus, multiple sclerosis, spondyloarthritis, irritable bowel syndrome). The potential mechanisms that underlie host-microbiota interaction are also discussed evaluate manipulation a therapeutic approach managing ADs. Additionally, this addresses current challenges microbiota-host research future recommendations. Recent Findings findings suggested pathogenesis ADs appears be multifaceted involving both genetic environmental factors. Dysbiosis or imbalanced has been increasingly identified one main factors can modulate responses contribute Summary New highlighted significance microbial etiology numerous diseases. Understanding relationship between host, however, goes beyond taxonomic concerns, demanding multidisciplinary efforts design new approaches take individual variances into account.

Язык: Английский

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A dynamic atlas of immunocyte migration from the gut

Science Immunology, Год журнала: 2024, Номер 9(91)

Опубликована: Янв. 5, 2024

Dysbiosis in the gut microbiota affects several systemic diseases, possibly by driving migration of perturbed intestinal immunocytes to extraintestinal tissues. Combining Kaede photoconvertible mice and single-cell genomics, we generated a detailed map migratory trajectories from colon, at baseline, models inflammation. All lineages emigrated colon an S1P-dependent manner. B lymphocytes represented largest contingent, with unexpected circulation nonexperienced follicular cells, which carried gut-imprinted transcriptomic signature. T cell emigration included distinct groups RORγ

Язык: Английский

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