DNA damage response signaling: A common link between cancer and cardiovascular diseases

Cancer Medicine, Journal Year: 2022, Volume and Issue: 12(4), P. 4380 - 4404

Published: Sept. 26, 2022

Abstract DNA damage response (DDR) signaling ensures genomic and proteomic homeostasis to maintain a healthy genome. Dysregulation either in the form of down‐ or upregulation DDR pathways correlates with various pathophysiological states, including cancer cardiovascular diseases (CVDs). Impaired is studied as signature mechanism for cancer; however, it also plays role ischemia‐reperfusion injury (IRI), inflammation, function, aging, demonstrating complex intriguing relationship between pathophysiology CVDs. Accordingly, there are increasing number reports indicating higher incidences CVDs patients. In present review, we thoroughly discuss (1) different pathways, (2) functional cross talk among mechanisms, (3) cancer, (4) commonalities differences CVDs, (5) (6) interventional strategies targeting instability (7) future perspective.

Language: Английский

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p53 contributes to cardiovascular diseases via mitochondria dysfunction: A new paradigm

Free Radical Biology and Medicine, Journal Year: 2023, Volume and Issue: 208, P. 846 - 858

Published: Sept. 29, 2023

Cardiovascular diseases (CVDs) are leading causes of global mortality; however, their underlying mechanisms remain unclear. The tumor suppressor factor p53 has been extensively studied for its role in cancer and is also known to play an important regulating CVDs. Abnormal expression levels modifications contribute the occurrence development Additionally, mounting evidence underscores critical involvement mitochondrial dysfunction Notably, studies indicate that abnormalities directly correlate with may even interact each other. Encouragingly, small molecule inhibitors targeting have exhibited remarkable effects animal models Moreover, therapeutic strategies aimed at mitochondrial-related molecules replacement therapy demonstrated advantageous potential. Therefore, or mitochondria holds immense promise as a pioneering approach combating In this comprehensive review, we delve into how influences dysfunction, including energy metabolism, oxidative stress, mitochondria-induced apoptosis, autophagy, dynamics, various Furthermore, summarize discuss potential significance treatment

Language: Английский

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Protective effect of secretory APE1/Ref‐1 on doxorubicin‐induced cardiotoxicity via suppression of ROS and p53 pathway

ESC Heart Failure, Journal Year: 2024, Volume and Issue: 11(2), P. 1182 - 1193

Published: Jan. 29, 2024

Abstract Aims The clinical application of doxorubicin (DOX), a potent anthracycline anticancer drug that effectively treats various malignancies, is limited by its side effects, such as cardiomyopathy. Apurinic/apyrimidinic endonuclease 1/redox factor‐1 (APE1/Ref‐1) multifunctional protein can be secreted and promising target for the reduction DOX‐induced inflammation oxidative stress. We aimed to investigate protective role secretory APE1/Ref‐1 against cardiac injury. Methods results Designated adenoviral preprotrypsin‐leading sequence (Ad‐PPTLS‐APE1/Ref‐1) was used overexpress assess in preventing cardiomyopathy vitro . Our findings revealed exposure significantly decreased N‐terminal pro‐B‐type natriuretic peptide levels DOX‐treated H9C2 cells. In addition, reduced severity cardiomyocyte injury apoptosis both vivo cardiotoxicity models. observed cardioprotective effects were mediated via inhibition p53 signalling pathway enhancement cell viability through attenuation stress cardiomyocytes. Conclusions study provides evidence has potential inhibit toxicity inhibiting related These suggest supplementation strategy attenuate damage preclinical model. Further investigations are essential validate therapeutic efficacy safety intervention human subjects.

Language: Английский

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“Unravelling the impacts of climatic heat events on cardiovascular health in animal models”

Environmental Research, Journal Year: 2024, Volume and Issue: 248, P. 118315 - 118315

Published: Feb. 1, 2024

Language: Английский

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Protein–protein interaction network-based integration of GWAS and functional data for blood pressure regulation analysis

Human Genomics, Journal Year: 2024, Volume and Issue: 18(1)

Published: Feb. 8, 2024

Abstract Background It is valuable to analyze the genome-wide association studies (GWAS) data for a complex disease phenotype in context of protein–protein interaction (PPI) network, as related pathophysiology results from function interacting polyprotein pathways. The analysis may include design and curation phenotype-specific GWAS meta-database incorporating genotypic eQTL linking PPI other biological datasets, development systematic workflows network-based integration toward protein pathway prioritization. Here, we pursued this blood pressure (BP) regulation. Methods relational scheme implemented Microsoft SQL Server BP-GWAS enabled combined storage of: attributes mined Catalog literature, Ensembl-defined SNP-transcript associations, GTEx data. BP-protein interactome was reconstructed PICKLE meta-database, extending GWAS-deduced network with shortest paths connecting all GWAS-proteins into one component. shortest-path intermediates were considered BP-related. For prioritization, new integrated GWAS-based scoring two criteria: considering role by (RbSP) novel promoting common neighbors GWAS-prioritized proteins. Prioritized proteins ranked number satisfied criteria. Results includes 6687 variants linked 1167 BP-associated protein-coding genes. 1065 proteins, 672 forming connected RbSP contains 1443 additional, network-deduced indicated that essentially are at most second neighbors. prioritized set derived union BP-significant any or included 335 ~ 2/3 deduced BP extension 126 least ESR1 only satisfying three criteria, followed top-10 INSR, PTN11, CDK6, CSK, NOS3, SH2B3, ATP2B1, FES FINC, two. Pathway revealed numerous bioprocesses, which indeed functionally supported BP-associated, our understanding about Conclusions workflow could be used multifactorial diseases.

Language: Английский

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Effects of essential oils on heat‐stressed poultry: A review

Journal of Animal Physiology and Animal Nutrition, Journal Year: 2024, Volume and Issue: 108(5), P. 1481 - 1497

Published: May 29, 2024

Abstract While certain animal species are sensitive to heat stress, poultry particularly modern breeds, more susceptible high ambient temperatures. This has major implications for the industry, as stress causes large financial losses. These economic losses will probably increase a consequence of predicted rise in global Heat adversely affects various aspects poultry, including physiological responses, growth and production performance, meat quality, egg reproductive activities. effects occur through specific molecular metabolic pathways. To mitigate impacts it is crucial go beyond administrative practices implement dietary interventions during temperature. Such aim optimize development stressed bird terms health, profitability. Essential oils have shown promising mitigating negative improved antioxidant status, yield well quality poultry. They actively participate pathways that help counteract stress. The article discusses essential oil supplementation on relationships between enzyme activity, these molecular, pathways, parameters such product heat‐stressed

Language: Английский

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A functional PVA aerogel-based membrane obtaining sutureability through modified electrospinning technology and achieving promising anti-adhesion effect after cardiac surgery

Bioactive Materials, Journal Year: 2021, Volume and Issue: 10, P. 355 - 366

Published: Aug. 19, 2021

Pericardial barrier destruction, inflammatory cell infiltration, and fibrous tissue hyperplasia, trigger adhesions after cardiac surgery. There are few anti-adhesion materials that both functional sutureable for pericardial reconstruction. Besides, a studies have reported on the mechanism of preventing adhesion. Herein, membrane with sutureability was developed via modified electrospinning method. It composed poly(l-lactide-co-caprolactone) (PLCL) nanofibers, poly(vinyl alcohol) (PVA) aerogel, melatonin, named PPMT. The PPMT had special microstructure manifested as staggered arrangement nanofibers surface layered macroporous aerogel structure in cross-section. Besides providing porosity hydrophilicity obtained from PVA, also suitable mechanical properties stitching due to addition PLCL nanofibers. Furthermore, it inhibited proliferation fibroblasts by suppressing activation Fas P53, achieved anti-inflammatory effects affecting activity cells reducing release pro-inflammatory factors, such interleukin 8 (IL-8) tumor necrosis factor α (TNF-α). Finally, vivo transplantation showed up-regulated expression matrix metalloproteinase-1 (MMP1) inhibitor (TIMP1), down-regulated Vinculin transforming growth β (TGF-β) myocardium, thereby formation adhesions. Collectively, these results demonstrate great potential practical application anti-adhesion.

Language: Английский

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Sirt6 protects cardiomyocytes against doxorubicin-induced cardiotoxicity by inhibiting P53/Fas-dependent cell death and augmenting endogenous antioxidant defense mechanisms

Cell Biology and Toxicology, Journal Year: 2021, Volume and Issue: 39(1), P. 237 - 258

Published: Oct. 28, 2021

Language: Английский

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Transcription Factors Involved in the Development and Prognosis of Cardiac Remodeling

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Feb. 2, 2022

To compensate increasing workload, heart must work harder with structural changes, indicated by size and changing shape, causing cardiac remodeling. However, pathological unlimited compensated remodeling will ultimately lead to decompensation failure. In the past decade, numerous studies have explored many signaling pathways involved in remodeling, but complete mechanism of is still unrecognized, which hinders effective treatment drug development. As gene transcriptional regulators, transcription factors control multiple cellular activities play a critical role This review summarizes regulation fetal reprogramming, energy metabolism, apoptosis, autophagy cardiomyocytes myofibroblast activation fibroblasts factors, an emphasis on their potential roles development prognosis

Language: Английский

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TRIM35-mediated degradation of nuclear PKM2 destabilizes GATA4/6 and induces P53 in cardiomyocytes to promote heart failure

Science Translational Medicine, Journal Year: 2022, Volume and Issue: 14(669)

Published: Nov. 2, 2022

Pyruvate kinase M2 (PKM2) is a glycolytic enzyme that translocates to the nucleus regulate transcription factors in different tissues or pathologic states. Although studied extensively cancer, its biological role heart remains unresolved. PKM1 more abundant than PKM2 isoform cardiomyocytes, and thus, we speculated not genetically redundant may be critical regulating cardiomyocyte-specific important for cardiac survival. Here, showed nuclear ( S37 P-PKM2) cardiomyocytes interacts with prosurvival proapoptotic factors, including GATA4, GATA6, P53. Cardiomyocyte-specific PKM2-deficient mice Pkm2 Mut Cre + ) developed age-dependent dilated dysfunction had decreased amounts of GATA4 GATA6 (GATA4/6) but increased P53 compared Control hearts. Nuclear prevented caspase-1–dependent cleavage degradation GATA4/6 while also providing molecular platform MDM2-mediated reduction In preclinical failure mouse model, were decreased, whereas was cardiomyocytes. Loss ubiquitination dependent associated induction E3 ubiquitin ligase TRIM35. mice, TRIM35 overexpression resulted P-PKM2 along littermate controls similar mice. patients left ventricles, increase This study supports previously unrecognized as mediates cell signaling events essential

Language: Английский

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