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The Hypoxia-Retinoid Axis in Idiopathic Pulmonary Fibrosis: Multifaceted Etiology and Therapeutic Potential.

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease with limited therapeutic options. This review focuses on the role of retinoids, particularly all-trans retinoic acid (atRA), and hypoxia in the pathogenesis of IPF. Despite an established understanding of genetic and environmental factors in IPF, the interplay between retinoid signaling and the response to hypoxia remains poorly explored due to its complexity. Preclinical evidence suggests that atRA could help reduce pulmonary fibrosis by modulating TGF-β signaling pathways and epithelial-to-mesenchymal transition (EM

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… Furthermore, cellular senescence has been observed in lung epithelium and mesenchymal cells of IPF patients, suggesting that senescent fibroblasts could be enough to start a progressive fibrogenic reaction in the lung [ 31 , 32 ]. 2. … Using the lung organoid model, it has been discovered that AE2 cells may have intermediate transition states associated with aging, cellular senescence, TGF-β, and HIF1 [ 126 ]. …

Association between Gut Microbiota and Biological Aging: A Two-Sample Mendelian Randomization Study.

Recent observational studies revealed an association between gut microbiota and aging, but whether gut microbiota are causally associated with the aging process remains unknown. We used a two-sample Mendelian randomization approach to investigate the causal association between gut microbiota and biological age acceleration using the largest available gut microbiota GWAS summary data from the MiBioGen consortium and GWAS data on biological age acceleration. We further conducted sensitivity analysis using MR-PRESSO, MR-Egger regression, Cochran Q test, and reverse MR analysis. Streptococcus (IVW

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… Cellular senescence and the senescent secretory phenotype: Therapeutic opportunities J. Clin. Investig. 2013 123 966 972 10.1172/JCI64098 23454759 PMC3582125 65. Yesilkaya H. Andisi V.F. Andrew P.W. Bijlsma J.J.E. … Cellular senescence in ageing: From mechanisms to therapeutic opportunities Nat. Rev. Mol. Cell Biol. 2021 22 75 95 10.1038/s41580-020-00314-w 33328614 PMC8344376 67. Connor M.G. Camarasa T.M.N. Patey E. Rasid O. Barrio L. Weight C.M. Miller D.P. Heyderman R.S. Lamont R.J. Enninga J. …

Chemotherapy Side-Effects: Not All DNA Damage Is Equal.

Recent advances have increased survival rates of children and adults suffering from cancer thanks to effective anti-cancer therapy, such as chemotherapy. However, during treatment and later in life they are frequently confronted with the severe negative side-effects of their life-saving treatment. The occurrence of numerous features of accelerated aging, seriously affecting quality of life, has now become one of the most pressing problems associated with (pediatric) cancer treatment. Chemotherapies frequently target and damage the DNA, causing mutations or genome instability, a major hallmark

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… Subsequently, DNA damage can result in (1) mutations and drive carcinogenesis or (2) impaired DNA replication, DNA and/or RNA synthesis, cell-cycle arrest, cellular senescence or cell death, and contribute to cellular or organ functional decline and accelerate aging. … Cellular senescence drives age-dependent hepatic steatosis Nat. Commun. 2017 8 15691 10.1038/ncomms15691 28608850 PMC5474745 96. Mollman J.E. Glover D.J. Hogan W.M. Furman R.E. Cisplatin neuropathy. …

ISEV2018 абстрактная книга

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Mechanisms of Chemotherapy-Induced Neurotoxicity.

Since the first clinical trials conducted after World War II, chemotherapeutic drugs have been extensively used in the clinic as the main cancer treatment either alone or as an adjuvant therapy before and after surgery. Although the use of chemotherapeutic drugs improved the survival of cancer patients, these drugs are notorious for causing many severe side effects that significantly reduce the efficacy of anti-cancer treatment and patients' quality of life. Many widely used chemotherapy drugs including platinum-based agents, taxanes, vinca alkaloids, proteasome inhibitors, and thalidomide ana

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… Lower doses of chemotherapy, similar to the levels of chemotherapeutic drugs found in the brain after systemic administration, may cause cellular senescence. Senescent cells are non-proliferating but remain metabolically active. …

Болезни Увечье с возрастом в экспериментальной модели множественного склероза: роль иммунозенсии.

Начавшийся множественный склероз (MS) у пожилых людей соотносится с более высоким риском развития первичных прогрессивных MS, ускорения перехода к вторичным прогрессивным MS и увеличения накопления инвалидности. Это явление может быть связано с возрастными изменениями в иммунной системе: с возрастом иммунная система проходит процесс, называемый иммунной сенсацией, который характеризуется снижением функции как врожденной, так и адаптивной иммунной реакции. Такое снижение может привести к снижению способности контролировать воспаление и восстанавливать поврежденные ткани. Кроме того, пожилые люд

The Landscape of lncRNAs in Multiple Myeloma: Implications in the "Hallmarks of Cancer", Clinical Perspectives and Therapeutic Opportunities.

Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides that are not translated into proteins. Nowadays, lncRNAs are gaining importance as key regulators of gene expression and, consequently, of several biological functions in physiological and pathological conditions, including cancer. Here, we point out the role of lncRNAs in the pathogenesis of multiple myeloma (MM). We focus on their ability to regulate the biological processes identified as "hallmarks of cancer" that enable malignant cell transformation, early tumor onset and progression. The aberrant expression of lncR

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… The updated version of “hallmarks of cancer” introduced cellular senescence as a new mechanism promoting malignant onset by the release of senescence-associated factors that modify the surrounding microenvironment [ 95 ]. … The Paradoxical Role of Cellular Senescence in Cancer. Front. Cell Dev. Biol. 2021;9:722205. doi: 10.3389/fcell.2021.722205. 96. Liu S., Otsuyama K., Ma Z., Abroun S., Shamsasenjan K., Amin J., Asaoku H., Kawano M.M. …

Tumor heterogeneity as a driver of drug resistance and its implications for personalized therapy.

Tumors are highly dynamic diseases characterized by significant heterogeneity. They consist of multiple cellular populations with distinct properties that respond differently to therapeutic pressure. This heterogeneity may arise from spatial variation across tumor regions (spatial heterogeneity) as well as from temporal changes during tumor evolution and treatment (temporal heterogeneity). As a consequence, drug-resistant subclones often emerge under therapy and contribute to treatment failure. Advances in single-cell and spatial multi-omics technologies enable precise quantification of tumor

Mesenchymal Stem Cell-Based Therapy for Kidney Disease: A Review of Clinical Evidence.

Mesenchymal stem cells form a population of self-renewing, multipotent cells that can be isolated from several tissues. Multiple preclinical studies have demonstrated that the administration of exogenous MSC could prevent renal injury and could promote renal recovery through a series of complex mechanisms, in particular via immunomodulation of the immune system and release of paracrine factors and microvesicles. Due to their therapeutic potentials, MSC are being evaluated as a possible player in treatment of human kidney disease, and an increasing number of clinical trials to assess the safety

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… Cellular senescence: when bad things happen to good cells. Nature Reviews Molecular Cell Biology. 2007;8(9):729–740. doi: 10.1038/nrm2233. 16. Le Blanc K., Frassoni F., Ball L., et al. …

Тайрозин Брютона: потенциальная новая цель для неврологических расстройств.

Тирозиновая киназа Брютона (BTK) является важной частью канала сигнала B-клектора, который широко изучался при различных видах недугов. Недавние исследования расширили наши знания о его роли в метаболизме, а также в неврологических расстройствах. Она может играть важную роль в патофизиологии неврологических заболеваний, таких как множественный склероз, болезнь Альцгеймера, повреждение мозга и несколько других. Активация воспалений, главным образом NLRP3, является одним из основных механизмов, с помощью которого она поощряет воспаление мозга, связанное со старением и болезнями. В настоящем доку

Specific epigenetic regulators serve as potential therapeutic targets in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF), a disorder observed mostly in older human beings, is characterised by chronic and progressive lung scarring leading to an irreversible decline in lung function. This health condition has a dismal prognosis and the currently available drugs only delay but fail to reverse the progression of lung damage. Consequently, it becomes imperative to discover improved therapeutic compounds and their cellular targets to cure IPF. In this regard, a number of recent studies have targeted the epigenetic regulation by histone deacetylases (HDACs) to develop and categorise

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… Thus, the studies using MSCs have also unravelled a functional role for one of the HDACs in regulating cellular senescence linked to IPF [ 262 ]. …

Application of Chimeric Antigen Receptor T Cells in the Treatment of Hematological Malignancies.

T cell immune protection plays a pivotal role in the treatment of patients with hematological malignancies. However, T cell exhaustion might lead to the possibility of immune escape of hematological malignancies. Adoptive cell therapy (ACT) with chimeric antigen receptor T (CAR-T) cells can restore the activity of exhausted T cell through reprogramming and is widely used in the treatment of relapsed/refractory (r/r) hematological malignancies. Of note, CD19, CD20, CD30, CD33, CD123, and CD269 as ideal targets have shown extraordinary potential for CAR-T cell therapy and other targets such as C

Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies.

Metastatic dissemination of solid tumors, a leading cause of cancer-related mortality, underscores the urgent need for enhanced insights into the molecular and cellular mechanisms underlying metastasis, chemoresistance, and the mechanistic backgrounds of individuals whose cancers are prone to migration. The most prevalent signaling cascade governed by multi-kinase inhibitors is the mitogen-activated protein kinase (MAPK) pathway, encompassing the RAS-RAF-MAPK kinase (MEK)-extracellular signal-related kinase (ERK) pathway. RAF kinase is a primary mediator of the MAPK pathway, responsible for th

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… Furthermore, the RAS/RAF/MAPK pathway is closely linked to the induction of cellular senescence, which is mediated by these CDK inhibitors, resulting in a premature G1 arrest. 214 Tumor ECM Degradation and angiogenesis Furthermore, the RAS/RAF/MAPK pathway plays a vital role in degradation of extracellular … senescence. 239 , 240 NF-κB activation promotes metastasis by increasing the expression of many metastatic genes, including cyclooxygenase 2 ( COX2) , genes encoding metalloproteinases, VEGF , and SNAIL . 241 , 242 Jacqueline’s group demonstrated that RAS can activate NF-κB transcriptional activity …

Роль неизлечимой терапии восстановления с помощью кладрибинных таблеток в борьбе с повторным множественным склерозом у пожилых пациентов.

Патофизиология и представление повторных множественных склерозов (RMS) существенно различаются между молодыми и пожилыми пациентами. Пожилые пациенты, как правило, страдают меньшим числом рецидивов MS, но имеют хронически воспалительный фенотип (инфламагирование), связанный с ускоренными возрастными изменениями адаптивной и врожденной иммунной системы (иммунонесценность). Как представляется, эффективность большинства методов коррекции заболеваний (ДМТ) снижается с увеличением возраста, что, вероятно, объясняется отходом от воспаления мозга в качестве основной движущей силы развития НР. В резул

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… Immunosenescence and inflammaging The term “cellular senescence” relates to a natural consequence of aging in which cells of the body become unable to replicate [ 30 ]. …

Using an integrated omics approach to uncover the mechanisms underlying chemotherapy-induced peripheral neuropathy (CIPN).

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect with limited treatment options. The primary challenge in developing therapies is the lack of identified neurotoxic mechanisms. To address this, an integrated omics approach, combining transcriptomics, proteomics, and metabolomics, is essential to map the biological changes underlying the condition. Here, we show how data from these complementary approaches converge on key mechanisms involved in CIPN through a critical summary of animal and human studies. Current research highlights several key drivers of CIPN, such

From Cells to Environment: Exploring the Interplay between Factors Shaping Bone Health and Disease.

The skeletal system is an extraordinary structure that serves multiple purposes within the body, including providing support, facilitating movement, and safeguarding vital organs. Moreover, it acts as a reservoir for essential minerals crucial for overall bodily function. The intricate interplay of bone cells plays a critical role in maintaining bone homeostasis, ensuring a delicate balance. However, various factors, both intrinsic and extrinsic, can disrupt this vital physiological process. These factors encompass genetics, aging, dietary and lifestyle choices, the gut microbiome, environment

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… Furthermore, telomere length, an indicator of cellular senescence, has been implicated as a marker of age-related disease progression. Numerous studies have indicated that telomere shortening impairs bone cell proliferation, differentiation, and normal function [ 19 , 20 ]. … Bone Aging, Cellular Senescence, and Osteoporosis. JBMR Plus. 2021;5:e10488. doi: 10.1002/jbm4.10488. 18. Pignolo R.J., Samsonraj R.M., Law S.F., Wang H., Chandra A. Targeting Cell Senescence for the Treatment of Age-Related Bone Loss. Curr. Osteoporos. …

The Confluence of Nanotechnology and Heat Shock Protein 70 in Pioneering Glioblastoma Multiforme Therapy: Forging Pathways Towards Precision Targeting and Transformation.

Heat-shock protein 70 (HSP70) and nanotechnology have emerged as promising avenues in glioblastoma multiforme (GBM) therapy, addressing the critical challenges posed by its aggressive nature and therapeutic resistance. HSP70's dual role in cellular stress response and tumour survival emphasises its potential as both a biomarker and therapeutic target. This review explores the innovative integration of HSP70 with nanotechnology, emphasising advancements in imaging, drug delivery and combination therapies. Nanoparticles, including SPIONs, liposomes, gold nanoparticles and metal-organic framework

Picropodophyllin inhibits the growth of pemetrexed-resistant malignant pleural mesothelioma via microtubule inhibition and IGF-1R-, caspase-independent pathways.

BackgroundAcquired pemetrexed resistance leads to treatment interruption in patients with malignant pleural mesothelioma (MPM). Insulin-like growth factor-I receptor (IGF-1R) inhibitor is a candidate for treating pemetrexed-naïve MPM. However, the efficacy of cytotoxic and targeted drugs in acquired-pemetrexed resistant MPM is unclear. We explored anticancer drugs, including the IGF-1R inhibitor picropodophyllin, against acquired pemetrexed-resistant MPMs.MethodsAcquired pemetrexed-resistant human MPM cell lines, named as H2452/PEM and 211H/PEM after their parental lines H2452 and 211H, respec

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… To evaluate PEM-induced cellular senescence, we measured SA-βGal activity. … Thus, PEM primarily promoted apoptosis in H2452 cells and induced G2/M phase arrest with cellular senescence in 211H cells but not in the PEM-resistant lines. These results consistently indicate that H2452/PEM and 211H/PEM cells are resistant to PEM and exhibit different characteristics. …

Нацеливание экспорта эндоплазмического ретикулума нарушает метаболическую устойчивость в множестве миэломы.

Множественная миелома (ММ) характеризуется производством и секрецией большого количества иммуноглобулинов, в результате чего эта злонамеренность в значительной степени зависит от механизмов, которые поддерживают клеточный протеостаз. Несмотря на значительный клинический прогресс, достигнутый в области деградативной ветки протеостаза, гораздо меньше внимания уделяется биосинтетической ветке. В этом исследовании мы продемонстрировали, что сдерживание экспорта эндоплазмического ретикулума (ER), зависящего от COPII, приводит к смерти клеток в нескольких линиях ММ и основных клеток, созданных пацие

Exosomes: A new option for osteoporosis treatment.

Osteoporosis is a systemic bone disease characterized by reduced bone mass and destruction of bone microarchitecture, leading to increased bone fragility and susceptibility to fracture. However, the pathogenesis and molecular mechanisms of this disease remain unclear. Extracellular vesicles, structures originating from the plasma membrane and ranging from 30 nm to 5 µm in diameter, play an important role in intercellular communication in the bone microenvironment. Exosomes are extracellular vesicles that deliver cargo molecules, including endogenous proteins, lipids and nucleic acids. These ca