Non-coding RNAs as therapeutic targets and biomarkers in ischaemic heart disease

Nature Reviews Cardiology, Год журнала: 2024, Номер 21(8), С. 556 - 573

Опубликована: Март 18, 2024

Язык: Английский

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Senescent cardiac fibroblasts: A key role in cardiac fibrosis

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2023, Номер 1869(4), С. 166642 - 166642

Опубликована: Янв. 18, 2023

Язык: Английский

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Whole-transcriptome sequencing in neural and non-neural tissues of a mouse model identifies miR-34a as a key regulator in SMA pathogenesis

Molecular Therapy — Nucleic Acids, Год журнала: 2025, Номер 36(2), С. 102490 - 102490

Опубликована: Фев. 20, 2025

Spinal muscular atrophy (SMA) is a severe neurodegenerative disorder caused by deficiency of survival motor neuron (SMN). While significant progress has been made in SMA therapy rescuing SMN expression, limited knowledge about downstream genes hindered the development alternative therapies. Here, we conducted whole-transcriptome sequencing spinal cord, heart, and liver tissues mouse model at early postnatal ages to explore critical coding non-coding RNAs (ncRNAs). A large number differentially expressed (DE-RNAs) were obtained, including 2,771 mRNAs, 382 microRNAs (miRNAs), 1,633 long ncRNAs, 1,519 circular RNAs. Through in-depth data mining, unveiled deregulation miR-34a all tissues. Analysis competitive endogenous RNA networks DE-RNAs identified multiple novel targets Spag5 mRNA, lncRNA00138536, circRNA007386. Further vitro studies using myoblast human cardiomyocyte cell lines showed that knockdown upregulated miR-34a-5p overexpression alone disrupted cell-cycle progression through regulating its targets, recapitulating gene expression patterns observed cardiac tissue mice. Our results miRNA involved pathology, which sheds insights into molecular basis widespread abnormalities forms SMA.

Язык: Английский

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Nutraceutical activation of Sirt1: a review

Open Heart, Год журнала: 2022, Номер 9(2), С. e002171 - e002171

Опубликована: Дек. 1, 2022

The deacetylase sirtuin 1 (Sirt1), activated by calorie restriction and fasting, exerts several complementary effects on cellular function that are favourable to healthspan; it is often thought of as an ‘anti-aging’ enzyme. Practical measures which might boost Sirt1 activity therefore considerable interest. A number nutraceuticals have potential in this regard. Nutraceuticals reported enhance synthesis or protein expression include ferulic acid, tetrahydrocurcumin, urolithin A, melatonin, astaxanthin, carnosic acid neochlorogenic acid. half-life can be enhanced with the natural nicotinamide catabolite N1-methylnicotinamide. availability Sirt1’s obligate substrate NAD+ increased ways: riboside mononucleotide substrates for synthesis; activators AMP-activated kinase—such berberine—can increase phosphoribosyltransferase, rate limiting nutraceutical quinones such thymoquinone pyrroloquinoline quinone promoting oxidation NADH. Induced ketosis—as via ingestion medium-chain triglycerides—can brain lessening reduction mediated glycolysis. Post-translational modifications O-GlcNAcylation sulfonation its activity, suggesting administration glucosamine agents hydrogen sulfide may aid activity. Although resveratrol has poor pharmacokinetics, bind activate allosterically—as so-called sirtuin-activating compound drugs. Since oxidative stress reduce multiple ways, effective antioxidant supplementation blunts also help preserve some circumstances. Combination regimens providing physiologically meaningful doses these agents, capable activating health promotion. Such amplify benefits sodium-glucose cotransporter-2 (SGLT2) inhibitors non-diabetic disorders, appear reflect upregulation kinase activities.

Язык: Английский

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Melatonin ameliorates arsenic‐induced cardiotoxicity through the regulation of the Sirt1/Nrf2 pathway in rats

BioFactors, Год журнала: 2023, Номер 49(3), С. 620 - 635

Опубликована: Янв. 7, 2023

Abstract Chronic arsenic (As) exposure, mainly as a result of drinking contaminated water, is associated with cardiovascular diseases. Mitochondrial dysfunction, oxidative stress, inflammation, apoptosis, and autophagy have been suggested the molecular etiology As cardiotoxicity. Melatonin (Mel) powerful antioxidant. Mel improves diabetic cardiomyopathy, cardiac remodeling, heart failure. Following pre‐treatment (10, 20, or 30 mg/kg/day i.p.), rats were orally gavaged (15 mg/kg/day) for 28 days. Electrocardiographic findings showed that decreased As‐mediated QT interval prolongation. The effects on levels glutathione (GSH) malondialdehyde (MDA) reversed by pretreatment. also modulated Sirt1 Nrf2 expressions promoted As. down‐regulated markers such Beclin‐1 expression LC3‐II/I ratio. Moreover, cleaved‐caspase‐3 Bax/Bcl‐2 ratio was Reduced miR‐34a miR‐144 Mel. histopathological changes injury exposure moderated may improve As‐induced dysfunction through anti‐oxidative, anti‐apoptotic, anti‐autophagic mechanisms.

Язык: Английский

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A change of heart: understanding the mechanisms regulating cardiac proliferation and metabolism before and after birth

The Journal of Physiology, Год журнала: 2023, Номер 601(8), С. 1319 - 1341

Опубликована: Март 6, 2023

Mammalian cardiomyocytes undergo major maturational changes in preparation for birth and postnatal life. Immature contribute to cardiac growth via proliferation thus the heart has capacity regenerate. To prepare life, structural metabolic associated with increased output function must occur. This includes exit from cell cycle, hypertrophic growth, mitochondrial maturation sarcomeric protein isoform switching. However, these come at a price: loss of regenerative such that damage life is permanent. significant barrier development new treatments repair contributes failure. The transitional period cardiomyocyte complex multifaceted event. In this review, we focus on studies have investigated critical transition as well novel factors may regulate drive process. We also discuss potential use biomarkers detection myocardial infarction and, broader sense, cardiovascular disease.

Язык: Английский

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Accelerating Patterned Vascularization Using Granular Hydrogel Scaffolds and Surgical Micropuncture

Small, Год журнала: 2023, Номер 20(8)

Опубликована: Окт. 12, 2023

Abstract Bulk hydrogel scaffolds are common in reconstructive surgery. They allow for the staged repair of soft tissue loss by providing a base revascularization. Unfortunately, they limited both slow and random vascularization, which may manifest as treatment failure or suboptimal repair. Rapidly inducing patterned vascularization within biomaterials has profound translational implications current clinical paradigms scaleup regenerative engineering platforms. To address this long‐standing challenge, novel microsurgical approach granular scaffold (GHS) technology co‐developed to hasten pattern microvascular network formation. In surgical micropuncture (MP), targeted recipient blood vessels perforated using microneedle accelerate cell extravasation angiogenic outgrowth. By combining MP with an adjacent GHS precisely tailored void space architecture, formation assessed density, diameter, length, intercapillary distance is rapidly guided. This work opens new opportunities engineering, advancing surgery, medicine.

Язык: Английский

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The dysregulation of miRNAs in epilepsy and their regulatory role in inflammation and apoptosis

Functional & Integrative Genomics, Год журнала: 2023, Номер 23(3)

Опубликована: Авг. 31, 2023

Abstract Epilepsy is a neurological disorder that impacts millions of people worldwide, and it characterized by the occurrence recurrent seizures. The pathogenesis epilepsy complex, involving dysregulation various genes signaling pathways. MicroRNAs (miRNAs) are group small non-coding RNAs play vital role in regulation gene expression. They have been found to be involved epilepsy, acting as key regulators neuronal excitability synaptic plasticity. In recent years, there has growing interest exploring miRNA regulatory network epilepsy. This review summarizes current knowledge miRNAs inflammation apoptosis discusses its potential new avenue for developing targeted therapies treatment

Язык: Английский

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Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: A Systematic Review

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(18), С. 10948 - 10948

Опубликована: Сен. 19, 2022

Immune checkpoint inhibitors (ICIs) are an important advancement in the field of cancer treatment, significantly improving survival patients with a series advanced malignancies, like melanoma, non-small cell lung (NSCLC), hepatocellular carcinoma (HCC), renal (RCC), and Hodgkin lymphoma. ICIs act upon T lymphocytes antigen-presenting cells, targeting programmed death protein 1 (PD1), ligand (PD-L1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), breaking immune tolerance cells against malignant enhancing body’s own response. A variety cardiac-adverse effects associated ICI-based including pericarditis, arrhythmias, cardiomyopathy, acute coronary syndrome, myocarditis being most studied due to its often-unexpected onset severity. Overall, Myocarditis is rare but presents immune-related adverse event (irAE) that has high fatality rate. Considering rising number oncological treated severity their potential effects, good understanding continuous investigation cardiac irAEs utmost importance. This systematic review aimed revise recent publications (between 2016–2022) on ICI-induced toxicities highlight therapeutical approach evolution selected cases.

Язык: Английский

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Role of microRNA-34a in blood–brain barrier permeability and mitochondrial function in ischemic stroke

Frontiers in Cellular Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Окт. 19, 2023

Over the past decade, there has been an uptick in number of studies conducting research on role microRNA (miRNA) molecules stroke. Among these molecules, miR-34a emerged as a significant player, its levels have observed to exhibit substantial rise following ischemic events. Elevated found multiple effects, including modulation inflammatory involved post-stroke recovery process, well negative effects blood–brain barrier (BBB) permeability. Interestingly, increase appears BBB permeability post stroke, through effect mitochondrial function. The strength function is crucial for limiting para-cellular and maintaining structural integrity BBB. Furthermore, activation repair mechanisms reduction event damage depend healthy activity. This review aims emphasize involvement specifically interaction with genes cerebrovascular endothelial cells, function, lastly regulatory A comprehensive understanding contribution pathogenesis stroke holds value establishing foundation development future therapeutics diagnostic markers.

Язык: Английский

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