Extracellular matrix remodeling in tumor progression and immune escape: from mechanisms to treatments

Molecular Cancer, Год журнала: 2023, Номер 22(1)

Опубликована: Март 11, 2023

The malignant tumor is a multi-etiological, systemic and complex disease characterized by uncontrolled cell proliferation distant metastasis. Anticancer treatments including adjuvant therapies targeted are effective in eliminating cancer cells but limited number of patients. Increasing evidence suggests that the extracellular matrix (ECM) plays an important role development through changes macromolecule components, degradation enzymes stiffness. These variations under control cellular components tissue via aberrant activation signaling pathways, interaction ECM to multiple surface receptors, mechanical impact. Additionally, shaped regulates immune which results suppressive microenvironment hinders efficacy immunotherapies. Thus, acts as barrier protect from supports progression. Nevertheless, profound regulatory network remodeling hampers design individualized antitumor treatment. Here, we elaborate on composition ECM, discuss specific mechanisms remodeling. Precisely, highlight impact development, proliferation, anoikis, metastasis, angiogenesis, lymphangiogenesis, escape. Finally, emphasize "normalization" potential strategy for anti-malignant

Язык: Английский

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Transforming growth factor-β in myocardial disease

Nature Reviews Cardiology, Год журнала: 2022, Номер 19(7), С. 435 - 455

Опубликована: Янв. 4, 2022

Язык: Английский

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Fibrosis: Types, Effects, Markers, Mechanisms for Disease Progression, and Its Relation with Oxidative Stress, Immunity, and Inflammation

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(4), С. 4004 - 4004

Опубликована: Фев. 16, 2023

Most chronic inflammatory illnesses include fibrosis as a pathogenic characteristic. Extracellular matrix (ECM) components build up in excess to cause or scarring. The fibrotic process finally results organ malfunction and death if it is severely progressive. Fibrosis affects nearly all tissues of the body. associated with inflammation, metabolic homeostasis, transforming growth factor-β1 (TGF-β1) signaling, where balance between oxidant antioxidant systems appears be key modulator managing these processes. Virtually every system, including lungs, heart, kidney, liver, can affected by fibrosis, which characterized an excessive accumulation connective tissue components. Organ frequently caused remodeling, also linked high morbidity mortality. Up 45% fatalities industrialized world are damage any organ. Long believed persistently progressing irreversible, has now been revealed very dynamic preclinical models clinical studies variety systems. pathways from and/or main topics this review. Furthermore, different organs their effects was discussed. Finally, we highlight many principal mechanisms fibrosis. These could considered promising targets for development potential therapies important human diseases.

Язык: Английский

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Fibroblasts: Immunomodulatory factors in refractory diabetic wound healing

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Авг. 5, 2022

Diabetes is a systemic disease in which patients with diabetes may develop peripheral neuropathy of the lower extremities and vascular due to long-term continuous exposure high glucose. Delayed wound healing one major complications diabetes. Slow diabetic associated glucose toxicity. When condition deteriorates, patient needs be amputated, seriously affects quality life even endangers patient. In general, delayed lack chemokines, abnormal inflammatory response, angiogenesis epithelial formation, fibroblast dysfunction. The incidence several chronic debilitating conditions increasing diabetes, such as renal insufficiency, heart failure, hepatic insufficiency. Fibrosis an inappropriate deposition extracellular matrix (ECM) proteins. It common causing organ fibrotic mechanism fibroblasts involve direct activation permanent fibroblasts. also degeneration fibers after hyperglycemia stimulates immune cells, or organ-specific parenchymal cells. Numerous studies confirm that play essential role treating its complications. primary function construct reshape ECM. Nowadays, widespread use single-cell RNA sequencing (scRNA-seq), number have found become critical sentinel can detect not only regulation response but molecular pattern related injury. By exploring heterogeneity functional changes manuscript discusses used immunomodulatory factors refractory healing, providing new ideas for treatment healing.

Язык: Английский

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Diabetic cardiomyopathy: Early diagnostic biomarkers, pathogenetic mechanisms, and therapeutic interventions

Cell Death Discovery, Год журнала: 2023, Номер 9(1)

Опубликована: Июль 21, 2023

Abstract Diabetic cardiomyopathy (DCM) mainly refers to myocardial metabolic dysfunction caused by high glucose, and hyperglycemia is an independent risk factor for cardiac function in the absence of coronary atherosclerosis hypertension. DCM, which a severe complication diabetes, has become leading cause heart failure diabetic patients. The initial symptoms are inconspicuous, patients gradually exhibit left ventricular eventually develop total failure, brings great challenge early diagnosis DCM. To date, underlying pathological mechanisms DCM complicated have not been fully elucidated. Although there therapeutic strategies available treatment focused on controlling blood glucose lipids, lack effective drugs targeting injury. Thus, large percentage with inevitably failure. Given neglected symptoms, intricate cellular molecular mechanisms, drugs, it necessary explore diagnostic biomarkers, further understand signaling pathways involved pathogenesis summarize current strategies, new targeted interventions.

Язык: Английский

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Macrophages in cardiovascular diseases: molecular mechanisms and therapeutic targets

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Май 31, 2024

Abstract The immune response holds a pivotal role in cardiovascular disease development. As multifunctional cells of the innate system, macrophages play an essential initial inflammatory that occurs following injury, thereby inducing subsequent damage while also facilitating recovery. Meanwhile, diverse phenotypes and phenotypic alterations strongly associate with distinct types severity diseases, including coronary heart disease, valvular myocarditis, cardiomyopathy, failure, atherosclerosis aneurysm, which underscores importance investigating macrophage regulatory mechanisms within context specific diseases. Besides, recent strides single-cell sequencing technologies have revealed heterogeneity, cell–cell interactions, downstream therapeutic targets at higher resolution, brings new perspectives into macrophage-mediated potential Remarkably, myocardial fibrosis, prevalent characteristic most cardiac remains formidable clinical challenge, necessitating profound investigation impact on fibrosis In this review, we systematically summarize functional plasticity diseases unprecedented insights introduced by technologies, focus different causes characteristics especially relationship between inflammation (myocardial infarction, pressure overload, dilated diabetic cardiomyopathy aging) vascular injury (atherosclerosis aneurysm). Finally, highlight preclinical/clinical targeting strategies translational implications.

Язык: Английский

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Stress hyperglycemia ratio as a prognostic indicator for long-term adverse outcomes in heart failure with preserved ejection fraction

Cardiovascular Diabetology, Год журнала: 2024, Номер 23(1)

Опубликована: Фев. 13, 2024

Abstract Background Recent studies highlighted that stress hyperglycemia ratio (SHR) is a potential predictor for future risk in heart failure (HF) patients. However, its implications specifically HF with preserved ejection fraction (HFpEF) are not yet fully elucidated. We aimed to investigate the association between SHR and long-term clinical outcomes HFpEF Methods patients enrolled 2015 2023, were followed (mean 41 months) composite outcome of all-cause, cardiovascular mortality, rehospitalization. was established as acute-chronic glycemia from admission blood glucose glycated hemoglobin. The optimal cut-off predict based on event prediction determined through ROC analysis, cutoff identified at 0.99. effect adverse examined Cox hazards Kaplan-Meier survival methods. A Pearson correlation analysis conducted assess relationship severity HF, indicated by N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Furthermore, incremental prognostic value further assessed integrated discrimination improvement (IDI) net reclassification (NRI). Results Among 400 patients, 190 individuals (47.5%) encountered events over 41-month follow-up period. significantly elevated compared those without ( p < 0.001). All stratified into high n = 124) low 276) groups cutoff. group had higher incidence than (log-rank; Additional poorer prognosis left ventricular EF (LVEF) levels (50 LVEF 60) (SHR > 0.99) comparison other (log-rank In adjusted after accounting age, sex, diabetes, NT-proBNP, remained independently predictive (adjusted HR: 2.34, 95% CI 1.49–3.67; adding model MAGGIC score provided an predicting events. Additionally, displayed slight NT-proBNP. Conclusion Elevated associated increased readmission lower SHR. valuable tool stratifying risks among

Язык: Английский

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Cardiac Fibrosis in heart failure: Focus on non-invasive diagnosis and emerging therapeutic strategies

Molecular Aspects of Medicine, Год журнала: 2023, Номер 93, С. 101194 - 101194

Опубликована: Июнь 27, 2023

Heart failure is a leading cause of mortality and hospitalization worldwide. Cardiac fibrosis, resulting from the excessive deposition collagen fibers, common feature across spectrum conditions converging in heart failure. Eventually, either reparative or reactive nature, long-term cardiac fibrosis contributes to development progression associated with poor clinical outcomes. Despite this, specific antifibrotic therapies are lacking, making an urgent unmet medical need. In this context, better patient phenotyping needed characterize heterogenous features advance toward its personalized management. review, we will describe different phenotypes focus on potential usefulness imaging techniques circulating biomarkers for non-invasive characterization condition tracking impact. We also recapitulate effects existing non-heart drugs discuss strategies under preclinical targeting activation fibroblasts at levels, as well additional extracardiac processes.

Язык: Английский

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NPRC deletion attenuates cardiac fibrosis in diabetic mice by activating PKA/PKG and inhibiting TGF-β1/Smad pathways

Science Advances, Год журнала: 2023, Номер 9(31)

Опубликована: Авг. 2, 2023

Cardiac fibrosis plays a key role in the progression of diabetic cardiomyopathy (DCM). Previous studies demonstrated cardioprotective effects natriuretic peptides. However, peptide receptor C (NPRC) on cardiac DCM remains unknown. Here, we observed that myocardial NPRC expression was increased mice and patients with DCM.

Язык: Английский

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Central role of cardiac fibroblasts in myocardial fibrosis of diabetic cardiomyopathy

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Март 31, 2023

Diabetic cardiomyopathy (DCM), a main cardiovascular complication of diabetes, can eventually develop into heart failure and affect the prognosis patients. Myocardial fibrosis is factor causing ventricular wall stiffness in DCM. Early control myocardial DCM great significance to prevent or postpone progression failure. A growing body evidence suggests that cardiomyocytes, immunocytes, endothelial cells involve fibrogenic actions, however, cardiac fibroblasts, participants collagen production, are situated most central position fibrosis. In this review, we systematically elaborate source physiological role fibroblasts context DCM, also discuss potential action mechanism promoting fibrosis, so as provide guidance for formulating strategies prevention treatment

Язык: Английский

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