Role of microRNAs in Immune Regulation with Translational and Clinical Applications

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1942 - 1942

Published: Feb. 5, 2024

MicroRNAs (miRNAs) are 19-23 nucleotide long, evolutionarily conserved noncoding RNA molecules that regulate gene expression at the post-transcriptional level. In this review, involvement of miRNAs is summarized in differentiation and function immune cells, anti-infective responses, immunodeficiencies autoimmune diseases. Roles anticancer immunity transplantation solid organs hematopoietic stem cells also discussed. Major focus put on translational clinical applications miRNAs, including establishment noninvasive biomarkers for differential diagnosis prediction prognosis. Patient selection response to biological therapy one most promising fields application. Replacement or inhibition has enormous therapeutic potential, with constantly expanding possibilities. Although important challenges still await solutions, evaluation miRNA fingerprints may contribute an increasingly personalized management dysregulation a remarkable reduction toxicity treatment side effects. More detailed knowledge molecular effects physical exercise nutrition system facilitate self-tailored lifestyle recommendations advances prevention.

Language: Английский

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Exercise Inhibits Doxorubicin-Induced Cardiotoxicity via Regulating B Cells

Circulation Research, Journal Year: 2024, Volume and Issue: 134(5), P. 550 - 568

Published: Feb. 7, 2024

Doxorubicin is an effective chemotherapeutic agent, but its use limited by acute and chronic cardiotoxicity. Exercise training has been shown to protect against doxorubicin-induced cardiotoxicity, the involvement of immune cells remains unclear. This study aimed investigate role exercise-derived B in protecting cardiotoxicity further determine whether cell activation antibody secretion play a this protection.

Language: Английский

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Molecular insights of exercise therapy in disease prevention and treatment

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 29, 2024

Despite substantial evidence emphasizing the pleiotropic benefits of exercise for prevention and treatment various diseases, underlying biological mechanisms have not been fully elucidated. Several attributed to signaling molecules that are released in response by different tissues such as skeletal muscle, cardiac adipose, liver tissue. These molecules, which collectively termed exerkines, form a heterogenous group bioactive substances, mediating inter-organ crosstalk well structural functional tissue adaption. Numerous scientific endeavors focused on identifying characterizing new mediators with properties. Additionally, some investigations molecular targets exerkines cellular cascades trigger adaption processes. A detailed understanding tissue-specific downstream effects is crucial harness health-related mediated improve targeted programs health disease. Herein, we review current vivo exerkine-induced signal transduction across multiple target highlight preventive therapeutic value exerkine diseases. By aspects research, provide comprehensive overview (i) underpinnings secretion, (ii) receptor-dependent receptor-independent adaption, (iii) clinical implications these disease treatment.

Language: Английский

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Altered atlas of exercise-responsive microRNAs revealing miR-29a-3p attacks armored & cold tumors and boosts anti-B7-H3 therapy

Research, Journal Year: 2025, Volume and Issue: 8

Published: Jan. 1, 2025

Increasing evidence has shown that physical exercise remarkably inhibits oncogenesis and progression of numerous cancers exercise-responsive microRNAs (miRNAs) exert a marked role in exercise-mediated tumor suppression. In this research, expression prognostic values miRNAs were examined breast cancer (BRCA) further pan-cancer types. addition, multiple independent public in-house cohorts, vitro assays involving multiple, macrophages, fibroblasts, cells, vivo models utilized to uncover the tumor-suppressive roles miR-29a-3p cancers. Here, we reported was miRNA, which lowly expressed tissues associated with unfavorable prognosis BRCA. Mechanistically, targeted cells down-regulate B7 homolog 3 (B7-H3) expression. Single-cell RNA sequencing (scRNA-seq) cytometry by time-of-flight (CyTOF) demonstrated attacked armored cold tumors, thereby shaping an immuno-hot microenvironment (TME). Translationally, liposomes developed loaded (lipo@miR-29a-3p), lipo@miR-29a-3p exhibited promising antitumor effects mouse model great biocompatibility. conclusion, uncovered is critical tumors inhibiting B7-H3 Thus, restoration could be alternative strategy for therapy.

Language: Английский

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ExerGeneDB: A physical exercise-regulated differential gene expression database

Journal of sport and health science/Journal of Sport and Health Science, Journal Year: 2025, Volume and Issue: unknown, P. 101027 - 101027

Published: Jan. 1, 2025

Exercise induces molecular changes that involve multiple organs and tissues. Moreover, these are modulated by various exercise parameters-such as intensity, frequency, mode, duration-as well clinical features like gender, age, body mass index (BMI), each eliciting distinct biological effects. To assist researchers in understanding from a comprehensive perspective includes organs, diverse regimens, range of features, we developed Regulated Genes Database (ExerGeneDB), database exercise-regulated differential genes. ExerGeneDB aggregated publicly available exercise-related sequencing datasets subjected them to uniform quality control preprocessing. The data, encompassing variety types, were organized into specialized Notably, conducted analyses on this collected leveraging curated information accounting for important factors such BMI. has assembled 1692 samples rats mice 4492 human samples. It contains data tissues skeletal muscle, blood, adipose tissue, intestine, heart, liver, spleen, lungs, kidneys, brain, spinal cord, bone marrow, bones. bulk Ribonucleic acid (RNA-seq) (including non-coding RNA (ncRNA) protein-coding RNA), microarray ncRNA single cell RNA-seq data. compiles re-analyzes with focus information. This culminated the creation an interactive regulation website can be found at: https://exergenedb.com.

Language: Английский

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Targeting B7-H3 inhibition-induced activation of fatty acid synthesis boosts anti-B7-H3 immunotherapy in triple-negative breast cancer

Journal for ImmunoTherapy of Cancer, Journal Year: 2025, Volume and Issue: 13(4), P. e010924 - e010924

Published: April 1, 2025

Triple-negative breast cancer (TNBC) is the most malignant cancer, highlighting need for effective immunotherapeutic targets. The immune checkpoint molecule B7-H3 has recently gained attention as a promising therapeutic target due to its pivotal role in promoting tumorigenesis and progression. However, impact of inhibitors (B7-H3i) remains unclear. Transcriptomic metabolomic analyses were conducted explore underlying mechanisms inhibition TNBC. efficacy combined treatment strategy was substantiated through comprehensive phenotypic assays vitro validated vivo using animal models. blockade induces "primed death" stress state cells, leading distinct alterations metabolic pathways. Specifically, knockdown activated AKT signaling pathway upregulated sterol regulatory element-binding protein 1 (SREBP1), which turn elevated FASN expression. simultaneous both more effectively attenuated progression Our findings propose an "immune attack-metabolic compensation" dynamic model suggest feasibility dual-targeting that concurrently inhibits enhance TNBC patients.

Language: Английский

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MiR-421 mediates PM _2.5 -induced endothelial dysfunction via crosstalk between bronchial epithelial and endothelial cells

Inhalation Toxicology, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 10

Published: May 22, 2024

Objective PM2.5 is closely linked to vascular endothelial injury and has emerged as a major threat human health. Our previous research indicated that exposure induced an increased release of miR-421 from the bronchial epithelium. However, role in PM2.5-induced remains elusive.

Language: Английский

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Amplification-Free Strategy for miRNA Quantification in Human Serum Using Single Particle ICP–MS and Gold Nanoparticles as Labels

Analytical Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: July 19, 2024

MicroRNAs (miRNAs), which are short single-stranded RNA sequences between 18 and 24 nucleotides, known to play a crucial role in gene expression. Changes their expression not only involved many diseases but also as response physiological changes, such physical exercise. In this work, new analytical strategy for the sensitive specific analysis of miRNA human plasma is presented. The developed does depend on any nucleic acid amplification process can be obtained direct correlation number events by using single-particle ICP–MS measurements. high selectivity assay (up single nucleotide polymorphisms) achieved double hybridization target with complementary capture oligonucleotide that conjugated magnetic microparticle simultaneously reporter gold nanoparticle. Thanks novel approach followed method, stoichiometry oligonucleotide-nanoparticle conjugates need addressed quantification miRNA, represents big advantage over other similar methods. optimized method applied determination biomarker exercise non-spiked serum samples, results validated against rt-qPCR. sensitivity permits differentiation among sedentary sportive subjects. This general platform easily sequence modifying oligonucleotides, paving way multiple clinically interesting applications.

Language: Английский

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Combination of Evidence from Bibliometrics and Bioinformatics Analysis Identifies miR-21 as a Potential Therapeutical Target for Diabetes

Metabolites, Journal Year: 2024, Volume and Issue: 14(8), P. 403 - 403

Published: July 25, 2024

Many microRNAs (miRNAs) have been identified as being involved in diabetes; however, the question of which ones may be most promising therapeutical targets still needs more investigation. This study aims to understand overall development tendency and identify a specific miRNA molecule attenuate diabetes. We developed combined analysis method based on bibliometrics bioinformatics visualize research institutions, authors, cited references, keywords target for Our data showed that diabetes-related is receiving continuously increasing attention, with large number publications, indicating this hot topic diabetes research. Scientists from different institutions are collaborating closely field. miR-21, miR-146a, miR-155, miR-34a frequently mentioned high-frequency related references. Moreover, among all above miRNAs, further strengthens argument miR-21 top significantly upregulated patients plays an important role pathogenesis provide way promote clinical translation miRNA-related strategies diabetes, could also indicate present future directions area.

Language: Английский

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Intradialytic exercise in haemodialysis patients: applicability and effects on muscle function

Published: May 28, 2024

Chronic kidney disease (CKD) negatively impacts quality of life and increases mortality risks, while the financial costs nephrology care dialysis therapy strain healthcare system patients. Haemodialysis is one renal replacement options for CKD patients with established failure. Dialysis therapy- disease-related complications contribute to patients' sedentary behaviour poor muscle functions (MF), which their frailty. This associated increased risks hospitalisation, mortality. Promotion physical activity has a strong potential suppress deterioration in MF. In this thesis, we explored effects intradialytic exercise (IDE) on MF, roles age, sex gene expression profile these effects. We further surveyed providers' perceptions benefits, barriers IDE. found that IDE prevented loss particularly middle-aged female patients, higher specific microribonucleic acid (miRNA-206). Healthcare were benefits mostly related psychosocial functioning, predominantly regarded exercise-related damage vascular access points. Limitations personal resources frequently reported as barriers. Our findings show might be effective preventing MF deterioration, especially if prescriptions are personalised regarding patient's socio-demographic genetic factors. Safe sustainable implementation requires adjustments minimise risk injury, alignment planned activities clinical profile, adequate availability resources.

Language: Английский

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