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Иммунометаболизм в старении мозга и нейродегенерации: преодоление метаболических путей и иммунные ответные меры.

Сложный набор взаимодействий между иммунной системой и метаболизмом, известный как иммунометаболизм, стал критическим регулятором последствий заболеваний в центральной нервной системе. В ходе многочисленных исследований метаболические расстройства увязывались с ослабленной иммунной реакцией при старении мозга, нейродегенеративных расстройствах и травме мозга. В этом обзоре мы обсудим вопрос о том, как нарушения баланса иммунометаболизма мозга способствуют патофизиологии дисфункции мозга. В первой части обзора резюмируется вклад таких критических групп иммунной клетки, как микроглии, астроциты,

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… Exercise plasma boosts memory and dampens brain inflammation via clusterin . Nature , 600 : 494 - 499 . 34880498 10.1038/s41586-021-04183-x PMC9721468 [79] Kalsbeek MJT , Mulder L , Yi C-X ( 2016 ). Microglia energy metabolism in metabolic disorder . …

Machine Learning Approaches in Diagnosis, Prognosis and Treatment Selection of Cardiac Amyloidosis.

Cardiac amyloidosis is an uncommon restrictive cardiomyopathy featuring an unregulated amyloid protein deposition that impairs organic function. Early cardiac amyloidosis diagnosis is generally delayed by indistinguishable clinical findings of more frequent hypertrophic diseases. Furthermore, amyloidosis is divided into various groups, according to a generally accepted taxonomy, based on the proteins that make up the amyloid deposits; a careful differentiation between the various forms of amyloidosis is necessary to undertake an adequate therapeutic treatment. Thus, cardiac amyloidosis is thou

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… Clusterin, fibulin-1, vitronectin, complement component C9, three collagen proteins, as well as the well-known amyloid signature proteins apolipoprotein E, apolipoprotein A4, and serum amyloid P were discovered as novel “amyloid signature” proteins using a Boruta method applied on a random forest classifier …

Curcumin Nanoparticles as Promising Therapeutic Agents for Drug Targets.

Curcuma longa is very well-known medicinal plant not only in the Asian hemisphere but also known across the globe for its therapeutic and medicinal benefits. The active moiety of Curcuma longa is curcumin and has gained importance in various treatments of various disorders such as antibacterial, antiprotozoal, cancer, obesity, diabetics and wound healing applications. Several techniques had been exploited as reported by researchers for increasing the therapeutic potential and its pharmacological activity. Here, the dictum is the new room for the development of physicochemical, as well as biolo

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… Moreover, it was also found that the expression of Apolipoprotein J or clusterin was decreased, thereby reducing the severity of the disease. …

Green Tea Catechins for Prostate Cancer Prevention: Present Achievements and Future Challenges.

Green tea catechins (GTCs) are a family of chemically related compounds usually classified as antioxidant molecules. Epidemiological evidences, supported by interventional studies, highlighted a more than promising role for GTCs in human prostate cancer (PCa) chemoprevention. In the last decades, many efforts have been made to gain new insights into the mechanism of action of GTCs. Now it is clear that GTCs' anticancer action can no longer be simplistically limited to their direct antioxidant/pro-oxidant properties. Recent contributions to the advancement of knowledge in this field have shown

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… The chemopreventive action of catechins in the TRAMP mouse model of prostate carcinogenesis is accompanied by clusterin over-expression Carcinogenesis 2004 25 2217 2224 10.1093/carcin/bgh235 15358631 13. Ahmad N. Feyes D.K. Nieminen A.L. Agarwal R. Mukhtar H. …

Diverse antitumor effects of ascorbic acid on cancer cells and the tumor microenvironment.

Ascorbic acid has attracted substantial attention for its potential antitumor effects by acting as an antioxidant in vivo and as a cofactor in diverse enzymatic reactions. However, solid proof of its clinical efficacy against cancer and the mechanism behind its effect have not been established. Moreover, cancer forms cancer-specific microenvironments and interacts with various cells, such as cancer-associated fibroblasts (CAFs), to maintain cancer growth and progression; however, the effect of ascorbic acid on the cancer microenvironment is unclear. This review discusses the effects and mechan

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… Ascorbate induces apoptosis in melanoma cells by suppressing clusterin expression . Sci Rep ( 2017 ) 7 : 3671 . doi: 10.1038/s41598-017-03893-5 28623268 PMC5473908 63 Gerecke C Schumacher F Berndzen A Homann T Kleuser B . …

Bone Marrow Adipocytes, Adipocytokines, and Breast Cancer Cells: Novel Implications in Bone Metastasis of Breast Cancer.

Accumulating discoveries highlight the importance of interaction between marrow stromal cells and cancer cells for bone metastasis. Bone is the most common metastatic site of breast cancer and bone marrow adipocytes (BMAs) are the most abundant component of the bone marrow microenvironment. BMAs are unique in their origin and location, and recently they are found to serve as an endocrine organ that secretes adipokines, cytokines, chemokines, and growth factors. It is reasonable to speculate that BMAs contribute to the modification of bone metastatic microenvironment and affecting metastatic br

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… Clusterin confers resistance to TNF-alpha-induced apoptosis in breast cancer cells through NF-kappaB activation and Bcl-2 overexpression . J Chemother. ( 2012 ) 24 : 348 – 57 . 10.1179/1973947812Y.0000000049 23174100 116. Qiao Y He H Jonsson P Sinha I Zhao C Dahlman-Wright K . …

Dysregulated TRK signalling is a therapeutic target in CYLD defective tumours.

Individuals with germline mutations in the tumour-suppressor gene CYLD are at high risk of developing disfiguring cutaneous appendageal tumours, the defining tumour being the highly organised cylindroma. Here, we analysed CYLD mutant tumour genomes by array comparative genomic hybridisation and gene expression microarray analysis. CYLD mutant tumours were characterised by an absence of copy-number aberrations apart from LOH chromosome 16q, the genomic location of the CYLD gene. Gene expression profiling of CYLD mutant tumours showed dysregulated tropomyosin kinase (TRK) signalling, with overex

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… CLUL1 | 4.30 | Clusterin-like 1 (retinal) (CLUL1), transcript variant 2, mrna. DACT2 | 4.30 | Dapper, antagonist of beta-catenin, homolog 2 (Xenopus laevis) (DACT2), mrna. ADM2 | 4.25 | Adrenomedullin 2 (ADM2), mrna. SNX22 | 4.15 | Sorting nexin 22 (SNX22), mrna. …

Lipocalin 2-not only a biomarker: a study of current literature and systematic findings of ongoing clinical trials.

Lipocalin 2 (Lcn2), also known as neutrophil gelatinase-associated lipocalin, is an innate immune protein encoded by the LCN2 gene. In this study, we investigated various roles and functions of Lcn2 characterized in a systems-based format and evaluated its therapeutic potentials and clinical relevance for diagnosis and prognosis. An additional systematic presentation was presented for 70 ongoing clinical trials utilizing Lcn2 in the diagnostic and prognostic setting as a key outcome measure. With trials being conducted through December 2030, Lcn2 will become all the more relevant given its ass

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… Change of serum creatinine level [mg/dL]; change of serum urea level [mg/dL]; change of serum cystatin C level [mg/L]; measurement of urine creatinine level [g/L]; change of urine alpha-1-microglobulin (A1M); change of urine aquaporin 2 (AQP2) [ng/mL]; change of urine Caldesmon [ng/mL]; change of urine clusterin …

Advances in antisense oligonucleotide development for target identification, validation, and as novel therapeutics.

Antisense oligonucleotides (As-ODNs) are single stranded, synthetically prepared strands of deoxynucleotide sequences, usually 18-21 nucleotides in length, complementary to the mRNA sequence of the target gene. As-ODNs are able to selectively bind cognate mRNA sequences by sequence-specific hybridization. This results in cleavage or disablement of the mRNA and, thus, inhibits the expression of the target gene. The specificity of the As approach is based on the probability that, in the human genome, any sequence longer than a minimal number of nucleotides (nt), 13 for RNA and 17 for DNA, normal

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… , Multiple myeloma, NSCLC, AML RESTEN-MP | AVI | c-myc | MF | Systemic | Phase II | Restenosis ISIS 2503 | Isis | H-ras | PS | Systemic | Phase II | NSCLC, breast, colorectal and pancreatic cancer LErafAON-ETU | NeoPharm | raf kinase | PS | Systemic | Phase I | Advanced cancer OGX-011 | OncoGenex | Clusterin …

The Roles of EDA2R in Ageing and Disease.

Ageing is a complex biological process driven, in part, by inflammaging. Recent research identifies the ectodysplasin A2 receptor (EDA2R) as a key regulator of inflammaging and a novel biomarker of ageing, with its expression increasing with age across diverse tissues in humans and animal models. Elevated EDA2R gene expression is associated with accelerated ageing, cellular senescence, frailty, obesity, acne, radiation response and increased levels of inflammatory, renal, cardiac and vascular biomarkers. Similarly, elevated EDA2R protein levels, a critical component of the proteomic ageing clo

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… Other well‐established ageing biomarkers identified in multiple studies include A2M (Alpha‐2‐macroglobulin), ADIPO (Adiponectin), AHSG (Alpha‐2‐HS‐Glycoprotein), B2M (Beta‐2‐Microglobulin), CLU (Clusterin), CRP (C‐reactive protein), CST3 (Cystatin C), CTSB (Cathepsin B), GHR (Growth Hormone Receptor) …

Lost in Translation (LiT): IUPHAR Review 6.

Translational medicine is a roller coaster with occasional brilliant successes and a large majority of failures. Lost in Translation 1 ('LiT1'), beginning in the 1950s, was a golden era built upon earlier advances in experimental physiology, biochemistry and pharmacology, with a dash of serendipity, that led to the discovery of many new drugs for serious illnesses. LiT2 saw the large-scale industrialization of drug discovery using high-throughput screens and assays based on affinity for the target molecule. The links between drug development and university sciences and medicine weakened, but t

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… Renal function testing in man still relies, to a great extent, on measuring serum creatinine and GFR, although more sensitive biomarkers for renal tubular injury have been qualified in animals, for example, KIM‐1, albumin, total protein, β 2 ‐microglobulin, cystatin C, clusterin and trefoil factor‐3 …

RNA Therapeutics in Viral Infections and Cancer: Mechanisms, Challenges, and Prospects: A Review.

Background: RNA therapeutics represent a rapidly advancing field with significant potential for treating viral infections and cancer. This review examines the current landscape of RNA-based strategies, including siRNA, miRNA mimics, and antisense oligonucleotides. For viral infections, the focus is on hepatitis B (HBV) and C (HCV), HIV, and SARS-CoV-2. Approaches include targeting viral transcripts directly (e.g., siRNAs against HBV surface antigen) or host factors critical for viral replication (e.g., anti-miR-122 miravirsen for HCV). The successful development of mRNA vaccines for COVID-19 i

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… . | [ 147 ] Custirsen (OGX-011) | Clusterin | PS, 2′-MOE | Breast Cancer, Prostate Cancer, Non-small Cell Lung Cancer | I, II, III, completed | NCT01578655 , NCT01188187 , NCT00327340 , NCT00258375 , etc. | [ 148 ] Trabedersen (AP-12009, OT-101) | TGF-β2 | CED—convection-enhanced delivery | NSCLC, Pancreatic …

YKL-40-A Protein in the Field of Translational Medicine: A Role as a Biomarker in Cancer Patients?

YKL-40 is a 40 kDa glycoprotein produced by cancer cells, inflammatory cells and stem cells. It probably has a role in cell proliferation and differentiation, inflammation, protection against apoptosis, stimulation of angiogenesis, and regulation of extracellular tissue remodelling. Plasma levels of YKL-40 are often elevated in patients with localized or advanced cancer compared to age-matched healthy subjects. Several studies have demonstrated that high plasma YKL-40 is an independent prognostic biomarker of short survival in patients with different types of cancer. However, there is not yet

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… Clusterin plays an important role in hepatocellular carcinoma metastasis Oncogene 2006 25 1242 1250 10.1038/sj.onc.1209141 16247463 45. Schunkert H. Samani N.J. Elevated C-reactive protein in atherosclerosis – chicken or egg? Editorial N. Engl. J. …

RESEARCH COMMUNICATIONS OF THE 34th ECVIM-CA CONGRESS.

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… Retrospective Study ESVNU‐O‐9 | 11.50‐12.05 | Bernard | Effects and remanence of short‐course of telmisartan or benazepril on renal function of healthy dogs: a prospective, cross‐over, double‐masked, placebo‐controlled study Friday 6 September 2024 | | ESVNU‐O‐10 | 09.00‐09.15 | Gordin | Urinary Clusterin …

Exogenous Heat Shock Proteins in Oncology: Biological Roles and Clinical Implications.

Heat shock proteins (HSPs), particularly HSP70 and HSP90, are highly conserved molecular chaperones that protect cells from a wide range of stressors and maintain proteome homeostasis. In cancer, tumor cells frequently overexpress and actively release HSPs into the extracellular space and circulation in response to metabolic alterations, hypoxia, oxidative stress, and therapeutic interventions. Consequently, circulating HSP levels are often elevated in patients with malignancies compared with healthy individuals. This review summarizes current evidence on the diagnostic, prognostic, and predic

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… In breast cancer, eHSP90α cooperates with clusterin through LRP1 signaling to downregulate E-cadherin and upregulate mesenchymal markers (N-cadherin, Slug, Snail, ZEB1) [ 98 ]. In prostate cancer, eHSP90α suppresses E-cadherin through EZH2 [ 97 ]. …

Polyphenols as Antitumor Agents Targeting Key Players in Cancer-Driving Signaling Pathways.

Polyphenols constitute an important group of natural products that are traditionally associated with a wide range of bioactivities. These are usually found in low concentrations in natural products and are now available in nutraceuticals or dietary supplements. A group of polyphenols that include apigenin, quercetin, curcumin, resveratrol, EGCG, and kaempferol have been shown to regulate signaling pathways that are central for cancer development, progression, and metastasis. Here, we describe novel mechanistic insights on the effect of this group of polyphenols on key elements of the signaling

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… Possible chemoprotective activity by reduction of tumor biomarkers PCNA and clusterin | Demonstration of EGCG levels in plasma, urine, and bladder tissue and the establishment of a dose-response relationship, as did modulation of tissue biomarkers of proliferation and apoptosis. …

Nanotechnology in Prostate Cancer: PSMA-Targeted Nanoplatforms, TME-Responsive Therapy, Immunomodulation, and Clinical Translation Challenges.

The field of nanotechnology has demonstrated considerable potential in the diagnosis and treatment of prostate cancer, particularly through the use of prostate-specific membrane antigen (PSMA)-targeted platforms and tumor microenvironment (TME)-responsive systems. In the context of diagnosis, nanoparticle-based molecular imaging probes have been shown to enhance detection sensitivity and specificity. These probes include superparamagnetic iron oxide, which is utilized in magnetic resonance imaging, and near-infrared fluorescent nanomicelles. Additionally, nanostructured liquid biopsy systems h

Hematology

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Pituitary Adenylate Cyclase-Activating Polypeptide: 30 Years in Research Spotlight and 600 Million Years in Service.

Emerging from the depths of evolution, pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors (i.e., PAC1, VPAC1, VPAC2) are present in multicellular organisms from Tunicates to humans and govern a remarkable number of physiological processes. Consequently, the clinical relevance of PACAP systems spans a multifaceted palette that includes more than 40 disorders. We aimed to present the versatility of PACAP1-38 actions with a focus on three aspects: (1) when PACAP1-38 could be a cause of a malfunction, (2) when PACAP1-38 could be the cure for a malfunction, and (3) when PA

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… PACAP inhibits tumor growth and interferes with clusterin in cervical carcinomas FEBS Lett. 2014 588 4730 4739 10.1016/j.febslet.2014.11.004 25451228 31. Germano P.M. Le S.V. Oh D.S. Fan R. Lieu S. Siu A. Pisegna J.R. …

Hematology

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