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Acute kidney injury: pathogenesis and therapeutic interventions.

Acute kidney injury (AKI) is a prevalent clinical condition that is associated with unacceptably high morbidity and mortality, as well as the development of chronic kidney disease (CKD). The pathogenesis of AKI is highly complex and heterogeneous, primarily attributed to metabolic disturbances arising from the disease itself and the administration of medications related to treatment. In recent years, AKI in cancer patients is highly concerned. The emergence of AKI caused injuries and dysfunction of remote organs but also enhanced the health-care costs. It's essential for early recognition of A

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… Cellular senescence represents an irreversible state of cell cycle arrest characterized by changes at transcriptional, metabolic, and secretory levels, as well as alterations in cellular morphology and chromatin organization. … Preliminary animal studies have highlighted the presence of cellular senescence in AKI, underscoring its significant impact on disease prognosis [ 169 ]. …

Geriatric assessments and frailty scores in multiple myeloma patients: a needed tool for individualized treatment?

PURPOSE OF REVIEW: Multiple myeloma is a disease of elderly adults. Improvement in survival has occurred because of biological insights and novel agents. Therapeutic options involve choices today, thus have become more complex. Demographics have led to an increased number of elderly patients and age may be associated with a poorer outcome but is not the only prognostic predictor today. RECENT FINDINGS: To evaluate patients' health status rather than their chronological age alone, frailty scores and functional geriatric assessments are used to identify prognostic groups, avoid adverse events,

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… Current biomarkers of inflammation, cellular senescence, endocrine, genomic and immune profiles are examined and displayed in Fig. 1 b [ 6 , 7 ▪ ]. …

Molecular mechanisms of the preventable causes of cancer in the United States.

Annually, there are 1.6 million new cases of cancer and nearly 600,000 cancer deaths in the United States alone. The public health burden associated with these numbers has motivated enormous research efforts into understanding the root causes of cancer. These efforts have led to the recognition that between 40% and 45% of cancers are associated with preventable risk factors and, importantly, have identified specific molecular mechanisms by which these exposures modify human physiology to induce or promote cancer. The increasingly refined knowledge of these mechanisms, which we summarize here,

Quantification of cell-free DNAfor the analysis of CD19-CAR-T cells during lymphoma treatment.

Chimeric antigen receptor (CAR)-T cells are increasingly used for the treatment of hematologic malignancies. Treatment success relies highly upon sufficient expansion of CAR-T effector cells. Accordingly, longitudinal quantification of CAR-T cells during therapy is clinically important. Techniques to quantify CAR-T cells in patient blood samples are based on flow cytometry and PCR. However, cellular kinetics of CAR-T cells are very complex and under current investigation. In this study, feasibility of CAR-T cell quantification by cell-free DNA (cfDNA) was analyzed. cfDNA isolated from 74 blood

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… In contrast, other therapies cause cytostatic effects and cellular senescence without the release of cfDNA. 26 Cytotoxic T cells induce apoptosis rapidly via FAS-Ligand and the perforin/granzyme pathway. …

Clinical Outcomes and Treatment Strategies of Adult Transplant-Associated Thrombotic Microangiopathy: External Validation of Harmonizing Definitions and High-Risk Criteria.

Transplant-associated thrombotic microangiopathy (TA-TMA) is an endothelial dysfunction syndrome observed after allogeneic hematopoietic cell transplant (alloHCT). Our aim was to externally validate the impact of high-risk features on the clinical outcomes of adult patients meeting the updated TA-TMA harmonizing criteria. Between 2005 and 2022, 99 patients were diagnosed with TA-TMA at Mayo Clinic Rochester (incidence 6.2%) after a median of 137 days post alloHCT (IQR: 34-283 days). The development of TA-TMA was associated with an inferior overall survival posttransplant (HR: 3.8, 95% CI: 2.97

Посттрансляционные изменения в нейроиммунных клетках во время нейроинфламмации: комплексные сети регулирования и терапевтические возможности.

Нейроинфламмация представляет собой общий патологический механизм, лежащий в основе широкого спектра нарушений центральной нервной системы (КНС), включая нейродегенеративные расстройства (НДД), ишемический инсульт (ИС), травматическое повреждение мозга (ТБИ) и демиелионирующие заболевания, такие как множественный склероз (МС). Этот процесс начинается с организованной реакции микроглий, астроцитов, олигодендроцитов, нейронов, эндотелиальных клеток головного мозга и проникновения в периферийные иммунные клетки. Нейроинфламмация может облегчить ремонт тканей или, наоборот, увековечить хроническое

Radiation-induced lung damage promotes breast cancer lung-metastasis through CXCR4 signaling.

Radiotherapy is a mainstay in the postoperative treatment of breast cancer as it reduces the risks of local recurrence and mortality after both conservative surgery and mastectomy. Despite recent efforts to decrease irradiation volumes through accelerated partial irradiation techniques, late cardiac and pulmonary toxicity still occurs after breast irradiation. The importance of this pulmonary injury towards lung metastasis is unclear. Preirradiation of lung epithelial cells induces DNA damage, p53 activation and a secretome enriched in the chemokines SDF-1/CXCL12 and MIF. Irradiated lung epith

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… An indicator of cellular senescence, p21, was maintained up to 4 days after irradiation, which explains the lower number of cells (Figure 1B, 1C and 1D ). Figure 1 Lung epithelial cells radiation response and senescence markers A. … In vitro experimentation on lung epithelial cells, the major pulmonary cell type, revealed potent H2AX and p53 responses to radiation which coincided with morphological changes, induction of cellular senescence markers and an enhanced secretion of multiple chemokines and growth factors. …

Абстрактный сборник ISEV2022.

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Comprehensive analysis of mRNA-microRNA-lncRNA expression profiles in post-traumatic elbow heterotopic ossification using RNA sequencing and experimental validation.

BackgroundThis study aimed to profile the molecular signatures of post-traumatic elbow heterotopic ossification (HO) to identify key regulators and potential therapeutic targets.MethodsTotal RNA from post-traumatic elbow HO tissues (n=4) and normal bone tissues (n=6) was subjected to high-throughput sequencing to identify differentially expressed mRNAs (DEGs), microRNAs (DEMs), and lncRNAs (DELs). Bioinformatics analyses included Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein-protein interaction network construction, and transcription factor (TF)

Translation of Epigenetics in Cell-Free DNA Liquid Biopsy Technology and Precision Oncology.

Technological advancements in cell-free DNA (cfDNA) liquid biopsy have triggered exponential growth in numerous clinical applications. While cfDNA-based liquid biopsy has made significant strides in personalizing cancer treatment, the exploration and translation of epigenetics in liquid biopsy to clinical practice is still nascent. This comprehensive review seeks to provide a broad yet in-depth narrative of the present status of epigenetics in cfDNA liquid biopsy and its associated challenges. It highlights the potential of epigenetics in cfDNA liquid biopsy technologies with the hopes of enha

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… The potency of cellular plasticity is also dictated by cellular senescence which is a hallmark of biological and chronological aging [ 51 , 52 ]. … Cellular senescence plays a key role in the regenerative capacity of tissues and may serve as a potential indicator of pathological tissue states and age-related diseases [ 51 , 52 , 53 ]. …

HMGB1: новая биомаркировка и лечебная цель аутоиммунной и аутовоспалительной кожных заболеваний.

Вставка 1 группы высокой подвижности (HMGB1) выражена почти во всех человеческих клетках. Во время активации клеток и клеточной смерти нуклеопротеин HMGB1 может перемещаться в внеклеточное пространство, тем самым посредничая ранним подстрекательским ответом как сигнализация или молекулярный рисунок, связанный с повреждением (DAMP). Внешнеклеточный HMGB1 взаимодействует с иммунными клетками, связываясь с системой распознавания рецепторов Toll-подобных (TLR), включая TLR2 и TLR4, и рецептором для современных продуктов для гликации (RAGE), тем самым содействуя иммунной реакции для защиты хоста от

Advances in Extracellular Matrix-Associated Diagnostics and Therapeutics.

The extracellular matrix (ECM) is the common denominator of more than 50 chronic diseases. Some of these chronic pathologies lead to enhanced tissue formation and deposition, whereas others are associated with increased tissue degradation, and some exhibit a combination of both, leading to severe tissue alterations. To develop effective therapies for diseases affecting the lung, liver, kidney, skin, intestine, musculoskeletal system, heart, and solid tumors, we need to modulate the ECM's composition to restore its organization and function. Across diverse organ diseases, there are common denom

Iron deprivation in cancer--potential therapeutic implications.

Iron is essential for normal cellular function. It participates in a wide variety of cellular processes, including cellular respiration, DNA synthesis, and macromolecule biosynthesis. Iron is required for cell growth and proliferation, and changes in intracellular iron availability can have significant effects on cell cycle regulation, cellular metabolism, and cell division. Perhaps not surprisingly then, neoplastic cells have been found to have higher iron requirements than normal, non-malignant cells. Iron depletion through chelation has been explored as a possible therapeutic intervention i

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… Cellular senescence as a tumor-suppressor mechanism. Trends Cell Biol. 2001;11:S27–S31. doi: 10.1016/s0962-8924(01)02151-1. 31. Lagger G., Doetzlhofer A., Schuettengruber B., Haidweger E., Simboeck E., Tischler J., Chiocca S., Suske G., Rotheneder H., Wintersberger E., et al. …

NAD+‒circadian rhythm coupling in dementia.

The circadian rhythm system and sleep coordinate whole-body functions across the 24-h cycle, yet these rhythms progressively deteriorate with neurodegenerative diseases, including dementia. Growing evidence indicates that nicotinamide adenine dinucleotide (NAD+) interacts with the circadian system through multiple molecular pathways and that NAD+ levels decline with dementia. In this review, we synthesize current evidence on the bidirectional relationship between NAD+ metabolism and circadian regulation in several dementia disorders, emphasizing the key circadian pathways, the nicotinamide pho

Иммунитет в нейромодуляции: исследование нейронных и иммунных путей в расстройствах мозга.

Иммунитет четко регулирует функцию мозга. Она непосредственно участвует в патологических процессах таких нейродегенеративных заболеваний, как болезнь Паркинсона и Альцгеймера, посттравматические заболевания, множественный склероз, травма головного мозга и психические расстройства (большое расстройство организма, серьезное депрессивное расстройство (МДС), расстройства тревожности, расстройства психоза и шизофрения, а также расстройства нервного развития (НРД). Нейромодулирование в настоящее время является одной из ведущих терапевтических стратегий лечения этих расстройств, однако пока мало что

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… Therefore, these insights demonstrate how neuroimmune mechanisms and cellular senescence contribute to neurodegeneration. We will analyze how neuromodulation techniques can be used to modulate these processes. …

Cardiotoxicity of Chemotherapy: A Multi-OMIC Perspective.

Chemotherapy-induced cardiotoxicity is a critical issue in cardio-oncology, as cancer treatments often lead to severe cardiovascular complications. Approximately 10% of cancer patients succumb to cardiovascular problems, with lung cancer patients frequently experiencing arrhythmias, cardiac failure, tamponade, and cardiac metastasis. The cardiotoxic effects of anti-cancer treatments manifest at both cellular and tissue levels, causing deformation of cardiomyocytes, leading to contractility issues and fibrosis. Repeated irradiation and chemotherapy increase the risk of valvular, pericardial, or

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… Fasudil Protects Against Adriamycin-induced Acute Heart Injury by Inhibiting Oxidative Stress, Apoptosis, and Cellular Senescence Curr. Pharm. Des. 2022 28 2426 2435 10.2174/1381612828666220729103430 35909282 48. Li M. Sala V. De Santis M.C. Cimino J. Cappello P. Pianca N. Di Bona A. Margaria J.P. …

Oxidative Stress: Signaling Pathways, Biological Functions, and Disease.

The dysregulated accumulation of reactive oxygen species (ROS) and reactive nitrogen species disrupts redox homeostasis, triggering oxidative stress (OS) and driving pathophysiological changes across multiple organ systems. OS modulates critical signaling pathways, induces inflammation, impairs mitochondrial function, alters metabolic homeostasis, and dysregulates autophagy, contributing to disease progression. While prior research has largely focused on OS within single-organ diseases (e.g., neurodegenerative, cardiovascular, and oncological disorders), the systemic role of OS in pan-organ di

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… Besides, OS can reshape the tumor microenvironment through induction of cellular senescence and the senescence‐associated secretory phenotype (SASP). …

Monoclonal Gammopathies and the Bone Marrow Microenvironment: From Bench to Bedside and Then Back Again.

Multiple myeloma (MM) is an incurable hematologic malignancy characterized by a multistep evolutionary pathway, with an initial phase called monoclonal gammopathy of undetermined significance (MGUS), potentially evolving into the symptomatic disease, often preceded by an intermediate phase called "smoldering" MM (sMM). From a biological point of view, genomic alterations (translocations/deletions/mutations) are already present at the MGUS phase, thus rendering their role in disease evolution questionable. On the other hand, we currently know that changes in the bone marrow microenvironment (TM

Mechanistic Insights into the Metabolic Pathways and Neuroprotective Potential of Pentacyclic Triterpenoids: In-Depth Analysis of Betulin, Betulinic, and Ursolic Acids.

Due to their complexity, both genotypic and phenotypic, neurodegenerative diseases are one of the main causes of death globally nowadays. Among phytochemicals of high scientific interest, based on experimental studies, pentacyclic triterpenoids (TTs), including mainly betulin, betulinic, and ursolic acid, became targets of scientific research in recent years, especially in terms of their biological activity and pharmacological potential. Due to their anti-inflammatory and antioxidant properties, as well as their involvement in cellular signal transductions, they have been observed to act as an

Пространственные омики нейроинфламмации: осмысления заболеваний мозга.

Нейроинфламмация является общей патологической особенностью различных заболеваний мозга, однако подстрекательская активность редко распределяется равномерно по заболевшим тканям. Вместо этого микроглии, астроциты, проникающие в иммунные клетки и подстрекательские посредники, часто организуются вокруг конкретных патологических структур, включая амилоидные таблетки, демиелинированные поражающие ободья, ишемические границы, некротические области опухоли и белые отсеки периваскулярной материи. Хотя в рамках одноклеточных подходов, основанных на оптовых и диссоциационных подходах, было определено м