Understanding Long COVID; Mitochondrial Health and Adaptation—Old Pathways, New Problems

Biomedicines, Journal Year: 2022, Volume and Issue: 10(12), P. 3113 - 3113

Published: Dec. 2, 2022

Many people infected with the SARS-CoV-2 suffer long-term symptoms, such as "brain fog", fatigue and clotting problems. Explanations for "long COVID" include immune imbalance, incomplete viral clearance potentially, mitochondrial dysfunction. As conditions sub-optimal function are associated initial severity of disease, their prior health could be key in resistance to long COVID recovery. The SARs virus redirects host metabolism towards replication; response, can metabolically react control virus. Resolution is normally achieved after stress activates a hormetic negative feedback mechanism. It therefore possible that, some individuals function, "tip" into chronic inflammatory cycle. This might explain main including platelet Long thus described virally induced self-perpetuating imbalanced non-resolving state characterised by dysfunction, where reactive oxygen species continually drive inflammation shift glycolysis. would suggest that sufferer's needs "tipped" back using stimulus, physical activity, calorie restriction, or chemical compounds mimic these enhancing perhaps combination inhibitors quell response.

Language: Английский

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Uropathogenic Escherichia coli infection-induced epithelial trained immunity impacts urinary tract disease outcome

Nature Microbiology, Journal Year: 2023, Volume and Issue: 8(5), P. 875 - 888

Published: April 10, 2023

Previous urinary tract infections (UTIs) can predispose one to future infections; however, the underlying mechanisms affecting recurrence are poorly understood. We previously found that UTIs in mice cause differential bladder epithelial (urothelial) remodelling, depending on disease outcome, impacts susceptibility recurrent UTI. Here we compared urothelial stem cell (USC) lines isolated from with a history of either resolved or chronic uropathogenic Escherichia coli (UPEC) infection, elucidating evidence molecular imprinting involved epigenetic changes, including differences chromatin accessibility, DNA methylation and histone modification. Epigenetic marks USCs chronically infected enhanced caspase-1-mediated death upon UPEC promoting bacterial clearance. Increased Ptgs2os2 expression also occurred, potentially contributing sustained cyclooxygenase-2 expression, inflammation mucosal wounding-responses associated severe cystitis. Thus, infection acts as an epi-mutagen reprogramming epigenome, leading urothelial-intrinsic remodelling training innate response subsequent infection.

Language: Английский

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Glycyrrhetinic Acid Liposomes Encapsulated Microcapsules from Microfluidic Electrospray for Inflammatory Wound Healing

Advanced Functional Materials, Journal Year: 2023, Volume and Issue: 33(43)

Published: June 25, 2023

Abstract In diabetic wound healing, M1 macrophage accumulation and elevated inflammation are prevalent issues. Intelligent delivery systems that can sustainably release antioxidizing anti‐inflammatory ingredients expected for effective healing. Herein, a novel glycyrrhetinic acid (GA) liposomes encapsulated microcapsules system has desired features inflammatory repair is presented. As the bacteria could break down alginate shells, GA be controllably released from microcapsules, which promotes M2 polarization regulate their responses in microenvironment. Based on these, it demonstrated exhibits an immunomodulatory effect healing full‐thickness defect model rats. These results indicate capabilities of unitized efficient repair, such valuable clinical applications.

Language: Английский

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Skin Barrier in Atopic Dermatitis

Journal of Investigative Dermatology, Journal Year: 2024, Volume and Issue: 144(5), P. 989 - 1000.e1

Published: April 19, 2024

Language: Английский

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CD80 on skin stem cells promotes local expansion of regulatory T cells upon injury to orchestrate repair within an inflammatory environment

Immunity, Journal Year: 2024, Volume and Issue: 57(5), P. 1071 - 1086.e7

Published: April 26, 2024

Following tissue damage, epithelial stem cells (SCs) are mobilized to enter the wound, where they confront harsh inflammatory environments that can impede their ability repair injury. Here, we investigated mechanisms protect skin SCs within this environment. Characterization of gene expression profiles hair follicle (HFSCs) migrated into wound site revealed activation an immune-modulatory program, including CD80, major histocompatibility complex class II (MHCII), and CXC motif chemokine ligand 5 (CXCL5). Deletion CD80 in HFSCs impaired re-epithelialization, reduced accumulation peripherally generated Treg (pTreg) cells, increased infiltration neutrophils wounded skin. Importantly, similar healing defects were also observed mice lacking pTreg cells. Our findings suggest upon injury, establish a temporary protective network by promoting local expansion thereby enabling re-epithelialization while still kindling inflammation outside niche until barrier is restored.

Language: Английский

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Inflammatory tissue priming: novel insights and therapeutic opportunities for inflammatory rheumatic diseases

Annals of the Rheumatic Diseases, Journal Year: 2024, Volume and Issue: 83(10), P. 1233 - 1253

Published: May 3, 2024

Due to optimised treatment strategies and the availability of new therapies during last decades, formerly devastating chronic inflammatory diseases such as rheumatoid arthritis or systemic sclerosis (SSc) have become less menacing. However, in many patients, even state-of-the-art cannot induce remission. Moreover, risk for flares strongly increases once anti-inflammatory therapy is tapered withdrawn, suggesting that underlying pathological processes remain active absence overt inflammation. It has evident tissues ability remember past encounters with pathogens, wounds other irritants, react more and/or persistently next occurrence. This priming tissue bears a paramount role defence from microbes, but on hand drives pathologies (the Dr Jekyll Mr Hyde aspect adaptation). Emerging evidence suggests long-lived tissue-resident cells, fibroblasts, macrophages, plasma cells memory T determine an interplay infiltrating immune lymphoid myeloid origin, systemically acting factors cytokines, extracellular vesicles antibodies. Here, we review current state science priming, focusing tissue-occupying SSc, reflect most promising options targeting maladapted response these diseases.

Language: Английский

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Regulation of dormancy during tumor dissemination: the role of the ECM

Cancer and Metastasis Reviews, Journal Year: 2023, Volume and Issue: 42(1), P. 99 - 112

Published: Feb. 21, 2023

Language: Английский

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Mitochondrial Calcium Ion Nanogluttons Alleviate Periodontitis via Controlling mPTPs

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(15)

Published: March 12, 2023

Abstract The mitochondrial permeability transition (mPT) directly affects function in macrophages. Under inflammatory conditions, calcium ion (mitoCa 2+ ) overload triggers the persistent opening of mPT pores (mPTPs), further aggravating Ca and increasing reactive oxygen species (ROS) to form an adverse cycle. However, there are currently no effective drugs targeting mPTPs confine or unload excess . It is novelly demonstrated that initiation periodontitis activation proinflammatory macrophages depend on overopening mPTPs, which mainly triggered by mitoCa facilitates ROS leakage into cytoplasm. To solve above problems, mitochondrial‐targeted “nanogluttons” with PEG‐TPP conjugated surface PAMAM BAPTA‐AM encapsulated core designed. These nanogluttons can efficiently “glut” around inside mitochondria effectively control sustained mPTPs. As a result, significantly inhibit Further studies also unexpectedly reveal alleviation local periodontal inflammation mice accompanied diminished osteoclast activity reduced bone loss. This provides promising strategy for mitochondria‐targeted intervention loss be extended treat other chronic diseases associated overload.

Language: Английский

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Patient-derived organoid biobank identifies epigenetic dysregulation of intestinal epithelial MHC-I as a novel mechanism in severe Crohn’s Disease

Gut, Journal Year: 2024, Volume and Issue: 73(9), P. 1464 - 1477

Published: June 10, 2024

Objective Epigenetic mechanisms, including DNA methylation (DNAm), have been proposed to play a key role in Crohn’s disease (CD) pathogenesis. However, the specific cell types and pathways affected as well their potential impact on phenotype outcome remain unknown. We set out investigate of intestinal epithelial DNAm CD Design generated 312 organoids (IEOs) from mucosal biopsies 168 patients with (n=72), UC (n=23) healthy controls (n=73). performed genome-wide molecular profiling DNAm, bulk single-cell RNA sequencing. Organoids were subjected gene editing functional consequences changes evaluated using an organoid-lymphocyte coculture nucleotide-binding oligomerisation domain, leucine-rich repeat CARD domain containing 5 (NLRC5) dextran sulphate sodium (DSS) colitis knock-out mouse model. Results identified highly stable, CD-associated loss at major histocompatibility complex (MHC) class 1 loci NLRC5 cognate upregulation. Single-cell sequencing primary tissue IEOs confirmed transcriptional transactivator epithelium. Increased MHC-I expression adult paediatric was validated additional cohorts highlighted by demonstrating relative protection DSS-mediated inflammation NLRC5-deficient mice. showed significant correlation outcomes. Application machine learning approaches enabled development prognostic epigenetic signature. Conclusions Our study has epigenetically regulated novel mechanism

Language: Английский

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Stemness in solid malignancies: coping with immune attack

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 25, 2024

Language: Английский

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