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Eternal Youth: A Comprehensive Exploration of Gene, Cellular, and Pharmacological Anti-Aging Strategies.

The improvement of human living conditions has led to an increase in average life expectancy, creating a new social and medical problem-aging, which diminishes the overall quality of human life. The aging process of the body begins with the activation of effector signaling pathways of aging in cells, resulting in the loss of their normal functions and deleterious effects on the microenvironment. This, in turn, leads to chronic inflammation and similar transformations in neighboring cells. The cumulative retention of these senescent cells over a prolonged period results in the deterioration of

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… Astroglial expression of clusterin ( Clu ) mediated by AAV was found to promote excitatory neurotransmission in wild-type mice and restore synaptic deficits in Clu knockout mice. … Clusterin secreted from astrocyte promotes excitatory synaptic transmission and ameliorates Alzheimer’s disease neuropathology Mol. Neurodegener. 2021 16 5 10.1186/s13024-021-00426-7 33517893 PMC7849119 154. Bartus R.T. Baumann T.L. Brown L. Kruegel B.R. Ostrove J.M. Herzog C.D. …

Spermidine/spermine N1-acetyltransferase-1 as a diagnostic biomarker in human cancer.

AimSSAT-1 is an enzyme that plays a critical role in cell growth. Amantadine, a FDA-approved antiviral drug, is a substrate for SSAT-1. The utility of amantadine as an agent to demonstrate elevated SSAT-1 activity linked to cancer was conducted.ResultsHigh levels of SSAT-1 expression were measured in tumor human cell lines, and in breast, prostate and lung tumor tissue. An increase in the urinary levels of acetylated amantadine in cancer patients was observed.ConclusionIncreases in SSAT-1 contents in tumor tissue could be of value in targeting cancers with high SSAT-1 expression for confirmati

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… Pharmacol. 65 10 2024 2035 1987 3322538 10.1139/y87-317 13 Bettuzzi S Davalli P Astancolle S Tumor progression is accompanied by significant changes in the levels of expression of polyamine metabolism regulatory genes and clusterin (sulfated glycoprotein 2) in human prostate cancer specimens Cancer …

Human-Induced Pluripotent Stem Cell Models for Amyloid Cardiomyopathy: From Mechanistic Insights to Therapeutic Discovery.

Amyloid cardiomyopathy (ACM), driven by transthyretin (TTR) and immunoglobulin light chain (LC) amyloid fibrils, remains a major clinical challenge due to limited mechanistic understanding and insufficient preclinical models. Human-induced pluripotent stem cells (iPSCs) have emerged as a transformative platform to model ACM, offering patient-specific and genetically controlled systems. In this review, we summarize recent advances in the use of iPSC-derived cardiomyocytes (iPSC-CMs) in both two-dimensional (2D) monolayer cultures and three-dimensional (3D) constructs-including spheroids, organo

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… Factors such as oxidative modifications (especially at Cys-10) [ 33 , 34 ], impaired chaperone activity (e.g., clusterin) [ 35 ], and protease-mediated cleavage [ 36 ] are believed to contribute to the destabilization of TTR wild-type tetramers and fibril formation in the heart. … Evidence for a functional role of the molecular chaperone clusterin in amyloidotic cardiomyopathy. Am. J. Pathol. 2011;178:61–68. doi: 10.1016/j.ajpath.2010.11.015. 36. …

Insulin-Like Growth Factor 2 mRNA-Binding Protein 3 Modulates Aggressiveness of Ewing Sarcoma by Regulating the CD164-CXCR4 Axis.

Ewing sarcoma (EWS) is the second most common bone and soft tissue-associated malignancy in children and young adults. It is driven by the fusion oncogene EWS/FLI1 and characterized by rapid growth and early metastasis. We have previously discovered that the mRNA binding protein IGF2BP3 constitutes an important biomarker for EWS as high expression of IGF2BP3 in primary tumors predicts poor prognosis of EWS patients. We additionally demonstrated that IGF2BP3 enhances anchorage-independent growth and migration of EWS cells suggesting that IGF2BP3 might work as molecular driver and predictor of E

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… family, VCAM1, GM-CSF receptor, PLAU (UPA), PI3K cat class IB (p110-gamma), CCL13 8 | Immune response_Alternative complement pathway | 53 | 2.9E−11 | 4.6E−09 | 16 | C5aR, C3a, C3, C5 convertase (C3b2Bb), Factor I, Factor Ba, C3b, CRIg, Factor Bb, C3aR, C3 convertase (C3bBb), iC3b, C3dg, Factor B, C3c, Clusterin …

Pathogenesis and kidney prognosis of renal amyloidosis.

Light chain (AL), serum amyloid A (AA), transthyretin (ATTR), leukocyte cell derived chemotaxin 2 (ALECT2), and fibrinogen Aa (AFib) amyloidosis are some of the most common types of protein-deposition disorders involving the kidney. Each amyloidogenic protein differs in its origin and little is known about the exact mechanisms that govern renal tropism and tissue injury for each amyloid subtype. While amyloidogenic precursor protein is different in each subtype of amyloidosis, its aggregation into fibrils depositing in target organs and leading to disruption of tissue architecture and progress

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… Guo J Guan Q Liu X Relationship of clusterin with renal inflammation and fibrosis after the recovery phase of ischemia-reperfusion injury BMC Nephrol 2016 17 133 10.1186/s12882-016-0348-x 27649757 PMC5028988 Guo J, Guan Q, Liu X et al (2016) Relationship of clusterin with renal inflammation and fibrosis …

Meibomian Gland Dysfunction Is Associated with Low Levels of Immunoglobulin Chains and Cystatin-SN.

Meibomian gland dysfunction (MGD) is a highly prevalent condition and the most common cause of evaporative dry eye disease. Studying the proteome of MGD can result in important advances in the management of the condition. Here, we collected tear film samples from treatment naïve patients with MGD (n = 10) and age-matched controls (n = 11) with Schirmer filtration paper. The samples were analyzed with label-free quantification nano liquid chromatography-tandem mass spectrometry. The proteins were considered differentially expressed if p < 0.05. A total of 88 proteins were significantly regulate

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… The overexpression of annexin-A1, clusterin, alpha-1-acid glycoprotein 1, and lactoperoxidase has previously been reported in MGD, while the downregulation of thioredoxin-1, Ig gamma-1, membrane-associated phospholipase A2, and antileukoproteinase has been reported. …

A Molecular Signature of Circulating MicroRNA Can Predict Osteolytic Bone Disease in Multiple Myeloma.

BACKGROUND: Multiple myeloma bone disease (MMBD) constitutes a common and severe complication of multiple myeloma (MM), impacting the quality of life and survival. We evaluated the clinical value of a panel of 19 miRNAs associated with osteoporosis in MMBD. METHODS: miRNAs were isolated from the plasma of 62 newly diagnosed MM patients with or without MMBD. First-strand cDNA was synthesized, and relative quantification was performed using qPCR. Lastly, we carried out extensive biostatistical analysis. RESULTS: Circulating levels of let-7b-5p, miR-143-3p, miR-17-5p, miR-214-3p, and miR-335-5p

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… High clusterin (CLU) mRNA expression levels in tumors of colorectal cancer patients predict a poor prognostic outcome Clin. Biochem. 2020 75 62 69 10.1016/j.clinbiochem.2019.10.008 31672651 32. Kalioraki M.A. Artemaki P.I. Sklirou A.D. Kontos C.K. Adamopoulos P.G. Papadopoulos I.N. Trougakos I.P. …

7-day longitudinal proteomics of critically ill patients: a pilot study.

An adult's health, indicated by measurable parameters, is stable over time. With the exception of circadian rhythms, variability in these pa … s. The effects of time on the protein level variances did not exceed 5%. Z-score-based hierarchical clustering analysis revealed that the daily data of each patient were clustered together indicating that the plasma proteome of ICU patients both bears individual traits and remains stable during short-term progression of the patients' condition. Therefore, i …

Direct Intercellular Communications and Cancer: A Snapshot of the Biological Roles of Connexins in Prostate Cancer.

Tissue homeostasis is the result of a complex intercellular network controlling the behavior of every cell for the survival of the whole organism. In mammalian tissues, cells do communicate via diverse long- and short-range communication mechanisms. While long-range communication involves hormones through blood circulation and neural transmission, short-range communication mechanisms include either paracrine diffusible factors or direct interactions (e.g., gap junctions, intercellular bridges and tunneling nanotubes) or a mixture of both (e.g., exosomes). Tumor growth represents an alteration

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… Moreover, in this study, the authors defined a series of events that involve stress-induced expression of chaperones, clusterin and the Y box binding protein 1 (YB-1) and AR variants, phophoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling, actin remodeling and TNT-mediated intercellular communication …

Biomarkers of Chemotherapy-Induced Peripheral Neuropathy: Current Status and Future Directions.

Chemotherapy induced peripheral neuropathy (CIPN) is an often severe and debilitating complication of multiple chemotherapeutic agents that can affect patients of all ages, across cancer diagnoses. CIPN can persist post-therapy, and significantly impact the health and quality of life of cancer survivors. Identifying patients at risk for CIPN is challenging due to the lack of standardized objective measures to assess for CIPN. Furthermore, there are no approved preventative treatments for CIPN, and therapeutic options for CIPN remain limited once it develops. Biomarkers of CIPN have been studie

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… Novel roles for osteopontin and clusterin in peripheral motor and sensory axon regeneration . J Neurosci. ( 2014 ) 34 : 1689 – 700 . 10.1523/JNEUROSCI.3822-13.2014 24478351 PMC3905142 30. Pizzamiglio C Ripellino P Prandi P Clemente N Saggia C Rossi V . …

Exosome-Enriched Hub Gene Networks Identify Diagnostic Biomarkers and Repurposable Therapeutic Targets in Endometriosis.

Endometriosis is a heterogeneous chronic inflammatory disorder associated with substantial diagnostic delay and limited therapeutic options, highlighting the need of robust non-invasive biomarkers and actionable molecular targets to complement existing low-sensitivity tests. To identify conserved pathogenic mechanisms with translational potential, here, we uniformly reprocessed three independent the Gene Expression Omnibus (GEO) microarray cohorts (GSE7305, GSE25628, and GSE11691) and applied a strict, directionally consistent intersection strategy to identify conserved transcriptional signals

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… adhesion, cell migration ExoCarta | Up | ADIRF | adipogenesis regulatory factor | 17.3 | 12.9 | 9.0 | None AKR1C1 | aldo-keto reductase family 1, member C1 | 2.9 | 5.9 | 2.2 | None CFD | complement factor D (adipsin) | 9.1 | 8.5 | 4.1 | None CFH | complement factor H | 36.3 | 6.0 | 4.4 | None CLU | clusterin …

Long Noncoding RNA 00472: A Novel Biomarker in Human Diseases.

Long non-coding RNAs (lncRNAs) play important roles in human diseases. They control gene expression levels and influence various biological processes through multiple mechanisms. Functional abnormalities in lncRNAs are strongly associated with occurrence and development of various diseases. LINC00472, which is located on chromosome 6q13, is involved in several human diseases, particularly cancers of the breast, lung, liver, osteosarcoma, bladder, colorectal, ovarian, pancreatic and stomach. Importantly, LINC00472 can be used as a biomarker for breast cancer cell sensitivity to chemotherapeutic

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… Clinical Importance of Serum Secreted Clusterin in Predicting Invasive Breast Cancer and Treatment Responses . Bioengineered 12 , 278 – 285 . 10.1080/21655979.2020.1868732 33356806 PMC8806267 Chen Z. Chen L. Sun B. Liu D. He Y. Qi L. ( 2021 ). …

Myelin Displacement and Revention in the Central Nervous System: Молекулярные механизмы, болезни и перспективные терапевтические цели.

Майлин пластичность имеет основополагающее значение для формирования нейронных сетей и оптимизации нейронных функций, формирования схем, регулирующих эмоции, сознание, сенсацию и управление двигателем. Подкомбинированный олигодендроцитами, миелин подвергается пожизненной реконструкции, которая требует высокой метаболической активности; это делает миелин-олигодендроцитную единицу весьма восприимчивой к метаболическому стрессу, старению и патологическим оскорблениям. Хотя обезвоживание является основной характеристикой различных хронических неврологических расстройств, в настоящем обзоре особо п

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… Additionally, other genes that increase the risk of AD including triggering receptor expressed on TREM2, clusterin (CLU), and phosphatidylinositol‐binding clathrin assembly protein (PICALM), all of which also affect the integrity of the myelin sheath [ 71 , 72 , 73 ]. …

Advances in antisense oligonucleotide treatment for cancer.

RNA therapeutics, including antisense oligonucleotides (ASOs), have emerged as a promising class of drugs, with several already approved for clinical use. To date, most approved ASO-based RNA therapies target non-malignant disorders such as neurodegenerative diseases, and only a single therapy in this class has been approved for cancer. Notably, nearly half of existing RNA therapeutics act by modulating RNA splicing. Given the growing evidence implicating aberrant RNA splicing in cancer pathogenesis, the development of ASO-based therapeutics for oncologic indications is expected to accelerate.

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… FDA approved Phase I/III , recruiting | [ 88 , 92 , 93 ] Danvatirsen (AZD9150) | STAT3 | DLBCL, NSCLC, HNSCC | Phase I/II , completed Phase I/II , recruiting | [ 94–96 ] Oblimersen (G3139, Genasense) | BCL2 | CLL, AML, non-Hodgkin lymphoma | Phase III , completed | [ 97 , 98 ] Custirsen (OGX-011) | Clusterin …

Микроэкология и тренировка: целевое воздействие на ось микробиота-Гут-Брэйна для лечения заболеваний центральной нервной системы.

Кишечная микробиота (ГМ) может играть решающую роль в развитии и развитии заболеваний центральной нервной системы (ЦНС). Микроэкология и упражнение могут влиять на состав и функции ГМ, оказывая тем самым позитивное воздействие на НКЦ. Ожидается, что комбинированные физические упражнения и микроэкология позволят более комплексно и эффективно решать проблемы, связанные с заболеваниями CNS, через ось микробиота-гут-мозгов (MMBA), потенциально превысив результаты отдельных мероприятий. Однако в настоящее время по этой теме не проводится соответствующих обзоров. В этом обзоре мы изучаем взаимосвязь

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… Some proteins in the serum showed a significant increase, including alpha-1 antitrypsin, fetuin A, vitamin D-binding protein, histidine-rich glycoprotein, apolipoprotein J (clusterin), apolipoproteins E and A1, and immunoglobulin J chain. …

Многофункциональная роль аполипопротеина Е в нейродегенеративных заболеваниях.

Генетическое разнообразие в гене аполипопротеина Е (АпоЭ) было определено в качестве основного фактора риска уязвимости в плане генетического риска для спорадического заболевания Альцгеймера (САД). В частности, аллея АпоЕ4 является важным фактором риска для SAD, в то время как аллея АпоЕ2 обеспечивает защиту по сравнению с более распространенными аллеями АпоЕ3. В настоящем обзоре рассматривается роль АпоЭ в АД и других нейродегенеративных расстройствах. ApoE — белок переноса холестерина — влияет на несколько путей нейродегенерации, особенно в AD. Помимо своей установленной роли в метаболизме и

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… Additionally, other identified ligands for TREM2 include ApoE, clusterin (CLU/ApoJ), Aβ, phosphatidylinositol, and phosphatidylcholine ( Ulland and Colonna, 2018 ; Gratuze et al., 2018 ). …

Chronic stress: a fourth etiology in tumorigenesis?

Chronic stress, driven by persistent psychological, environmental, or physiological factors, is a prolonged heightened state of stress response that disrupts homeostasis. When unmanaged, it will lead to sustained negative emotions such as depression, loneliness, anxiety, and emotional adversity. This persistent emotional distress not only exacerbates mental health disorders but also poses significant risks to physical health. Increasing evidence suggests a strong link between chronic stress, stress-related hormones, and the rising incidence of malignancies. As a result, chronic stress might be

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… Glucocorticoids drive upregulation of the therapy-resistance oncoproteins lens epithelium-derived growth factor p75 (LEDGF/p75) and clusterin (CLU) in prostate cancer cells via GR activation. … associated agonist of cell death Brain-derived-neurotrophic factor Cancer-associated fibroblasts Cyclic adenosine monophosphate Chemokine (C-C motif) ligand Cell-derived xenograft CCAAT enhancer-binding protein beta Cyclic guanosine 3’,5’-cyclic monophosphate Circadian locomotor output cycles kaput Clusterin …

Cancer Metabolism as a Therapeutic Target and Review of Interventions.

Cancer is amenable to low-cost treatments, given that it has a significant metabolic component, which can be affected through diet and lifestyle change at minimal cost. The Warburg hypothesis states that cancer cells have an altered cell metabolism towards anaerobic glycolysis. Given this metabolic reprogramming in cancer cells, it is possible to target cancers metabolically by depriving them of glucose. In addition to dietary and lifestyle modifications which work on tumors metabolically, there are a panoply of nutritional supplements and repurposed drugs associated with cancer prevention and

High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer.

Mounting evidence indicates that vitamin C has the potential to be a potent anti-cancer agent when administered intravenously and in high doses (high-dose IVC). Early phase clinical trials have confirmed safety and indicated efficacy of IVC in eradicating tumour cells of various cancer types. In recent years, the multi-targeting effects of vitamin C were unravelled, demonstrating a role as cancer-specific, pro-oxidative cytotoxic agent, anti-cancer epigenetic regulator and immune modulator, reversing epithelial-to-mesenchymal transition, inhibiting hypoxia and oncogenic kinase signalling and b

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… These analyses revealed, among others, deregulation of apoptotic gene clusterin as well as genes involved in extracellular matrix remodeling in melanoma cell line A2058, as well as increased TNF-related apoptosis-inducing ligand (TRAIL) transcripts in breast cancer cell line MDA-MB-231. …

Апиген как потенциальный модулятор нейроинфламмации в многоразовом склерозе: обзор.

Множественный склероз (MS) — хроническое воспалительное заболевание центральной нервной системы (CNS), характеризующееся нейроинфламмацией и обезвоживанием. Несмотря на то, что в течение последнего десятилетия расширились возможности лечения MS, нынешняя терапия направлена главным образом на периферийные иммунные системы и часто связана со значительными побочными эффектами. Кроме того, эта терапия до сих пор не предлагает решений для последующего нейродегенерации, сопровождающего развитие болезни. Результаты исследований, проведенных с использованием клеточных и животных моделей и исследований

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… Reactive astrocytes can also secrete clusterin (CLU), a glycoprotein highly elevated in active multiple sclerosis lesions that inhibits OPC differentiation directly, induces OPC and oligodendrocyte apoptosis through suppression of PI3K-AKT signaling, and concurrently impairs astrocyte-mediated clearance …