Epigenetic regulation in metabolic diseases: mechanisms and advances in clinical study

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 2, 2023

Abstract Epigenetics regulates gene expression and has been confirmed to play a critical role in variety of metabolic diseases, such as diabetes, obesity, non-alcoholic fatty liver disease (NAFLD), osteoporosis, gout, hyperthyroidism, hypothyroidism others. The term ‘epigenetics’ was firstly proposed 1942 with the development technologies, exploration epigenetics made great progresses. There are four main epigenetic mechanisms, including DNA methylation, histone modification, chromatin remodelling, noncoding RNA (ncRNA), which exert different effects on diseases. Genetic non-genetic factors, ageing, diet, exercise, interact jointly affect formation phenotype. Understanding could be applied diagnosing treating diseases clinic, biomarkers, drugs, editing. In this review, we introduce brief history well milestone events since proposal ‘epigenetics’. Moreover, summarise research methods general mechanisms modulation. Furthermore, interaction between genetic or factors. Finally, clinical trials applications

Language: Английский

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Large-scale plasma proteomics comparisons through genetics and disease associations

Nature, Journal Year: 2023, Volume and Issue: 622(7982), P. 348 - 358

Published: Oct. 4, 2023

High-throughput proteomics platforms measuring thousands of proteins in plasma combined with genomic and phenotypic information have the power to bridge gap between genome diseases. Here we performed association studies Olink Explore 3072 data generated by UK Biobank Pharma Proteomics Project

Language: Английский

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Small Molecule NF-κB Pathway Inhibitors in Clinic

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(14), P. 5164 - 5164

Published: July 21, 2020

Nuclear factor kappa B (NF-κB) signaling is implicated in all major human chronic diseases, with its role transcription of hundreds gene well established the literature. This has propelled research into targeting NF-κB pathways for modulating expression those genes and diseases mediated by them. In-spite critical, but often promiscuous played this pathway inhibition causing adverse drug reaction, currently many biologics, macromolecules, small molecules that modulate are market or clinical trials. Furthermore, marketed drugs were later found to also have activity repurposed new therapeutic interventions. Despite rising importance biologics discovery, got around 76% US-FDA (Food Drug Administration-US) approval last decade. encouraged us review information regarding clinically relevant molecule inhibitors from cell surface receptor stimulation nuclear signaling. We highlighted underexplored targets potential succeed clinic.

Language: Английский

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Novel insights into macrophage diversity in rheumatoid arthritis synovium

Autoimmunity Reviews, Journal Year: 2021, Volume and Issue: 20(3), P. 102758 - 102758

Published: Jan. 19, 2021

Language: Английский

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Antioxidant, Anti-Inflammatory, Anti-Menopausal, and Anti-Cancer Effects of Lignans and Their Metabolites

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(24), P. 15482 - 15482

Published: Dec. 7, 2022

Since chronic inflammation can be seen in severe, long-lasting diseases such as cancer, there is a high demand for effective methods to modulate inflammatory responses. Among many therapeutic candidates, lignans, absorbed from various plant sources, represent type of phytoestrogen classified into secoisolariciresionol (Seco), pinoresinol (Pino), matairesinol (Mat), medioresinol (Med), sesamin (Ses), syringaresinol (Syr), and lariciresinol (Lari). Lignans consumed by humans further modified END or ENL the activities gut microbiota. are known exert antioxidant anti-inflammatory activities, together with activity estrogen receptor-dependent pathways. may have potential postmenopausal symptoms, including cardiovascular disease, osteoporosis, psychological disorders. Moreover, antitumor efficacy lignans has been demonstrated cancer cell lines, hormone-dependent breast prostate well colorectal cancer. Interestingly, molecular mechanisms these involve inhibition signals, nuclear factor (NF)-κB pathway. Therefore, we summarize recent vitro vivo studies evaluating biological effects focusing on their values agents.

Language: Английский

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miRNAs insights into rheumatoid arthritis: Favorable and detrimental aspects of key performers

Life Sciences, Journal Year: 2022, Volume and Issue: 314, P. 121321 - 121321

Published: Dec. 24, 2022

Language: Английский

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Targeting strategies for bone diseases: signaling pathways and clinical studies

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 17, 2023

Abstract Since the proposal of Paul Ehrlich’s magic bullet concept over 100 years ago, tremendous advances have occurred in targeted therapy. From initial selective antibody, antitoxin to drug delivery that emerged past decades, more precise therapeutic efficacy is realized specific pathological sites clinical diseases. As a highly pyknotic mineralized tissue with lessened blood flow, bone characterized by complex remodeling and homeostatic regulation mechanism, which makes therapy for skeletal diseases challenging than other tissues. Bone-targeted has been considered promising approach handling such drawbacks. With deepening understanding biology, improvements some established bone-targeted drugs novel targets deliveries on horizon. In this review, we provide panoramic summary recent strategies based targeting. We highlight targeting structure biology. For agents, addition classic denosumab, romosozumab, PTH1R ligands, potential process key membrane expressions, cellular crosstalk, gene expression, all cells exploited. delivery, different matrix, marrow, are summarized comparison between ligands. Ultimately, review will summarize translation therapies perspective challenges application clinic future trends area.

Language: Английский

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Molecular and Cellular Mechanisms of Osteoporosis

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(21), P. 15772 - 15772

Published: Oct. 30, 2023

Osteoporosis is a widespread systemic disease characterized by decrease in bone mass and an imbalance of the microarchitecture tissue. Experimental clinical studies devoted to investigating main pathogenetic mechanisms osteoporosis revealed important role estrogen deficiency, inflammation, oxidative stress, cellular senescence, epigenetic factors development resorption due osteoclastogenesis, decreased mineralization tissue formation reduced function osteoblasts caused apoptosis age-depended differentiation osteoblast precursors into adipocytes. The current review was conducted describe basic at molecular levels elucidate most promising therapeutic strategies therapy based on articles cited PubMed up September 2023.

Language: Английский

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COVID-19 and Bone Loss: A Review of Risk Factors, Mechanisms, and Future Directions

Current Osteoporosis Reports, Journal Year: 2024, Volume and Issue: 22(1), P. 122 - 134

Published: Jan. 15, 2024

Abstract Purpose of Review SARS-CoV-2 drove the catastrophic global phenomenon COVID-19 pandemic resulting in a multitude systemic health issues, including bone loss. The purpose this review is to summarize recent findings related loss and potential mechanisms. Recent Findings early clinical evidence indicates an increase vertebral fractures, hypocalcemia, vitamin D deficiencies, BMD among patients. Additionally, lower associated with more severe infection. Preclinical models have shown increased osteoclastogenesis. infection could be result many factors that directly affect such as higher inflammation, activation NLRP3 inflammasome, recruitment Th17 cells, hypoxic environment, changes RANKL/OPG signaling. can exert indirect effects on skeleton, mechanical unloading may occur disease (e.g., bed rest) or BMI muscle wasting has also been Muscle cause issues influence bone. Medications used treat negative effect Lastly, worsen conditions diabetes negatively kidney function, all which contribute fracture risk. Summary through multiple direct Future work will needed determine what patient populations are at risk COVID-19-related increases risk, mechanisms behind loss, therapeutic options. This article part series manuscripts designed utility using artificial intelligence for writing scientific reviews.

Language: Английский

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Influence of the TGF-β Superfamily on Osteoclasts/Osteoblasts Balance in Physiological and Pathological Bone Conditions

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(20), P. 7597 - 7597

Published: Oct. 14, 2020

The balance between bone forming cells (osteoblasts/osteocytes) and resorbing (osteoclasts) plays a crucial role in tissue homeostasis repair. Several hormones, cytokines, growth factors-in particular the members of TGF-β superfamily such as morphogenetic proteins-not only regulate proliferation, differentiation, functioning these cells, but also coordinate communication them to ensure an appropriate response. Therefore, this review focuses on its influence formation repair, through regulation osteoclastogenesis, osteogenic differentiation stem osteoblasts/osteoclasts balance. After introducing main types their cooperation during remodeling fracture healing processes are discussed. Then, superfamily, signaling via canonical non-canonical pathways, well by Wnt/Notch or microRNAs described Its important homeostasis, disease is highlighted. Finally, clinical therapeutic uses associated complications debated.

Language: Английский

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