CAR-T Regulatory (CAR-Treg) Cells: Engineering and Applications DOI Creative Commons
Motahareh Arjomandnejad,

Acadia L. Kopec,

Allison M. Keeler

и другие.

Biomedicines, Год журнала: 2022, Номер 10(2), С. 287 - 287

Опубликована: Янв. 26, 2022

Regulatory T cells are critical for maintaining immune tolerance. Recent studies have confirmed their therapeutic suppressive potential to modulate responses in organ transplant and autoimmune diseases. However, the unknown nonspecific antigen recognition of polyclonal Tregs has impaired potency initial clinical findings. To address this limitation, specificity can be conferred by engineering expression transgenic T-cell receptor (TCR) or chimeric (CAR). In contrast TCR Tregs, CAR major histocompatibility complex (MHC) independent less dependent on interleukin-2 (IL-2). Furthermore, maintain Treg phenotype function, home target tissue show enhanced efficacy compared Tregs. Additional development engineered is needed increase Tregs’ function stability, prevent exhaustion, assess safety profile. Further understanding will necessary before moving broader applications. Here, we summarize recent utilizing modulating diseases, transplantation, gene therapy future

Язык: Английский

Stem cell-based therapy for human diseases DOI Creative Commons
Duc M. Hoang,

Phuong T. Pham,

Trung Q. Bach

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Авг. 6, 2022

Abstract Recent advancements in stem cell technology open a new door for patients suffering from diseases and disorders that have yet to be treated. Stem cell-based therapy, including human pluripotent cells (hPSCs) multipotent mesenchymal (MSCs), has recently emerged as key player regenerative medicine. hPSCs are defined self-renewable types conferring the ability differentiate into various cellular phenotypes of body, three germ layers. MSCs progenitor possessing self-renewal (limited vitro) differentiation potential lineages, according International Society Cell Gene Therapy (ISCT). This review provides an update on recent clinical applications using either or derived bone marrow (BM), adipose tissue (AT), umbilical cord (UC) treatment diseases, neurological disorders, pulmonary dysfunctions, metabolic/endocrine-related reproductive skin burns, cardiovascular conditions. Moreover, we discuss our own trial experiences targeted therapies setting, propose MSC origin concept how may contribute role downstream applications, with ultimate objective facilitating translational research medicine applications. The mechanisms discussed here support proposed hypothesis BM-MSCs potentially good candidates brain spinal injury treatment, AT-MSCs disorder regeneration, UC-MSCs disease acute respiratory distress syndrome treatment.

Язык: Английский

Процитировано

617

Hemicyanine‐Based Near‐Infrared Activatable Probes for Imaging and Diagnosis of Diseases DOI

Ziling Zeng,

Si Si Liew, Xin Wei

и другие.

Angewandte Chemie International Edition, Год журнала: 2021, Номер 60(51), С. 26454 - 26475

Опубликована: Июль 15, 2021

Molecular activatable probes with near-infrared (NIR) fluorescence play a critical role in vivo imaging of biomarkers for drug screening and disease diagnosis. With structural diversity high quantum yields, hemicyanine dyes have emerged as versatile scaffold the construction optical probes. This Review presents survey hemicyanine-based NIR (HNAPs) early diagnosis diseases. The molecular design principles HNAPs towards signaling against various are discussed focus on their broad applications detection diseases including inflammation, acute organ failure, skin diseases, intestinal cancer. progress not only proves unique value preclinical research but also highlights translational potential clinical

Язык: Английский

Процитировано

248

The influence of cytokines on the complex pathology of ulcerative colitis DOI Creative Commons
Hiroshi Nakase, Noriko Sato, Naomi Mizuno

и другие.

Autoimmunity Reviews, Год журнала: 2021, Номер 21(3), С. 103017 - 103017

Опубликована: Дек. 10, 2021

Ulcerative colitis (UC) specifically affects the colon and rectum through multifactorial mechanisms associated with genetic alterations, environmental factors, microbiota, mucosal immune dysregulation. In patients corticosteroid-refractory UC, current therapies primarily employ antibodies against tumor necrosis factor-α, α4β7 integrin, interleukin (IL)-12/23 p40; a small-molecule Janus kinase inhibitor. Despite these revolutionary molecular targeting introduced during last two decades, 30%–55% of fail to respond such agents in induction phase, requiring changes treatment. Here we review basic clinical research aimed address this problem, focusing on pathogenic effects cytokines produced by innate adaptive cells. For example, IL-1β, IL-6, T helper (Th) 1-, Th2-, Th17-associated are expressed at relatively higher levels intestinal tissues UC. However, their expression depend disease stage patient characteristics. The complex pathology UC may induce differences responses therapy. findings studies strongly support argument that future targeted must focus cytokine stages as well distinct profiles individual patients.

Язык: Английский

Процитировано

238

Ulcerative colitis: an update DOI Open Access
Jonathan Segal, Jean‐Frédéric LeBlanc, Ailsa Hart

и другие.

Clinical Medicine, Год журнала: 2021, Номер 21(2), С. 135 - 139

Опубликована: Март 1, 2021

ABSTRACT

Ulcerative colitis is a relapsing and remitting disease that increasing in incidence prevalence. Management aims to achieve rapid resolution of symptoms, mucosal healing improvement patient's quality life. 5-aminosalicylate acid medications remain the first-line treatment for mild moderate disease. In event suboptimal response these medications, escalation immunosuppressive biologics may be necessary. Importantly, despite best medical therapy, surgery required proportion patients. The future will likely see an array new therapeutic options those with ulcerative potential more personalised approach.

Язык: Английский

Процитировано

219

Kaempferol Alleviates Murine Experimental Colitis by Restoring Gut Microbiota and Inhibiting the LPS-TLR4-NF-κB Axis DOI Creative Commons

Yifan Qu,

Xinyi Li, Fengying Xu

и другие.

Frontiers in Immunology, Год журнала: 2021, Номер 12

Опубликована: Июль 22, 2021

Intestinal microbiota dysbiosis is an established characteristic of ulcerative colitis (UC). Regulating the gut attractive alternative UC treatment strategy, considering potential adverse effects synthetic drugs used to treat UC. Kaempferol (Kae) anti-inflammatory and antioxidant flavonoid derived from a variety medicinal plants. In this study, we determined efficacy mechanism action Kae as anti-UC agent in dextran sulfate sodium (DSS)-induced mice. DSS challenge mouse model led weight loss, diarrhea accompanied by mucous blood, histological abnormalities, shortening colon, all which were significantly alleviated pretreatment with Kae. addition, intestinal permeability was shown improve using fluorescein isothiocyanate (FITC)-dextran administration. DSS-induced destruction barrier also prevented administration via increases levels ZO-1, occludin, claudin-1. Furthermore, decreased IL-1β, IL-6, TNF-α downregulated transcription array inflammatory signaling molecules, while it increased IL-10 mRNA expression. Notably, reshaped microbiome elevating Firmicutes Bacteroidetes ratio; increasing linear discriminant analysis scores beneficial bacteria, such Prevotellaceae Ruminococcaceae; reducing richness Proteobacteria DSS-challenged There evident shift profile fecal metabolites group. Serum LPS downstream TLR4-NF-κB supplementation. Moreover, transplantation Kae-treated mice confirmed on modulating alleviate Therefore, may exert protective against through regulating TLR4-related pathways. This study demonstrates its therapeutic mechanisms, offers novel insights into prevention diseases natural products.

Язык: Английский

Процитировано

203

The Gut Microbiome and Inflammatory Bowel Diseases DOI Open Access
Yue Shan, Mirae Lee, Eugene B. Chang

и другие.

Annual Review of Medicine, Год журнала: 2021, Номер 73(1), С. 455 - 468

Опубликована: Сен. 23, 2021

Inflammatory bowel diseases (IBD) arise from a convergence of genetic risk, environmental factors, and gut microbiota, where each is necessary but not sufficient to cause disease. Emerging evidence supports bidirectional relationship between disease progression changes in microbiota membership function. Thus, the study microbiome host-microbe interactions should provide critical insights into pathogenesis as well leads for developing microbiome-based diagnostics interventions IBD. In this article, we review most recent advances understanding IBD highlight importance going beyond establishing description association gain mechanistic causes consequences The aims contextualize findings form conceptional frameworks etiopathogenesis future development interventions.

Язык: Английский

Процитировано

188

The metabolic nature of inflammatory bowel diseases DOI
Timon E. Adolph,

Moritz Meyer,

Julian Schwärzler

и другие.

Nature Reviews Gastroenterology & Hepatology, Год журнала: 2022, Номер 19(12), С. 753 - 767

Опубликована: Июль 29, 2022

Язык: Английский

Процитировано

173

Network Pharmacology Prediction and Molecular Docking-Based Strategy to Discover the Potential Pharmacological Mechanism of Huai Hua San Against Ulcerative Colitis DOI Creative Commons

Jiaqin Liu,

Jian Liu, Xiaoliang Tong

и другие.

Drug Design Development and Therapy, Год журнала: 2021, Номер Volume 15, С. 3255 - 3276

Опубликована: Июль 1, 2021

Huai Hua San (HHS), a famous Traditional Chinese Medicine (TCM) formula, has been widely applied in treating ulcerative colitis (UC). However, the interaction of bioactives from HHS with targets involved UC not elucidated yet.A network pharmacology-based approach combined molecular docking and vitro validation was performed to determine bioactives, key targets, potential pharmacological mechanism against UC.Bioactives HHS, as well UC-related were retrieved public databases. Crucial bioactive ingredients, signaling pathways acquired through bioinformatics analysis, including protein-protein (PPI), Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) analysis. Subsequently, carried out predict combination active compounds core targets. Lastly, experiments conducted further verify findings.A total 28 ingredients 421 HHS-UC-related screened. Bioinformatics analysis revealed that quercetin, luteolin, nobiletin may be candidate agents. JUN, TP53, ESR1 could become therapeutic PI3K-AKT pathway might play an important role UC. Moreover, suggested ESR1, respectively. Cell showed most ingredient inhibit levels inflammatory factors phosphorylated c-Jun, PI3K-Akt LPS-induced RAW264.7 cells, which confirmed prediction by pharmacology strategy docking.Our results comprehensively illustrated It also provided promising uncover scientific basis TCM formulae diseases.

Язык: Английский

Процитировано

169

Dopamine, Immunity, and Disease DOI Creative Commons

Breana Channer,

Stephanie Matt,

Emily Nickoloff-Bybel

и другие.

Pharmacological Reviews, Год журнала: 2022, Номер 75(1), С. 62 - 158

Опубликована: Дек. 8, 2022

The neurotransmitter dopamine is a key factor in central nervous system (CNS) function, regulating many processes including reward, movement, and cognition. Dopamine also regulates critical functions peripheral organs, such as blood pressure, renal activity, intestinal motility. Beyond these functions, growing body of evidence indicates that an important immunoregulatory factor. Most types immune cells express receptors other dopaminergic proteins, take up, produce, store, and/or release dopamine, suggesting immunomodulation for function. Targeting pathways could be promising avenue the treatment inflammation disease, but despite increasing research this area, data on specific effects disease remain inconsistent poorly understood. Therefore, review integrates current knowledge role cell function inflammatory signaling across systems. We discuss understanding regulation CNS tissues, highlighting diseases Parkinson’s several neuropsychiatric conditions, neurologic human immunodeficiency virus, bowel rheumatoid arthritis, others. Careful consideration given to influence experimental design results, we note number areas need further research. Overall, our immunology at cellular, tissue, level prompts development therapeutics strategies targeted toward ameliorating through immunity.

Significance Statement

Canonically, recognized involved cognition, reward. However, acts modulator periphery. This comprehensively assesses pathogenesis cellular tissue level. will provide broad access information fields, identify investigation, drive therapeutic strategies.

Язык: Английский

Процитировано

156

MUC2 and related bacterial factors: Therapeutic targets for ulcerative colitis DOI
Dianbo Yao,

Wanlin Dai,

Ming Dong

и другие.

EBioMedicine, Год журнала: 2021, Номер 74, С. 103751 - 103751

Опубликована: Дек. 1, 2021

Язык: Английский

Процитировано

155