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In-Depth Analysis of the Extracorporeal Proteome Adsorbed to Dialysis Membranes during Hemodialysis.

Used hemodialysis membranes (HD-M) are a valuable reservoir of biological information. Proteins bind to HD-M, but whether this process depends on the type of membrane or patient factors or selectively affects specific protein classes has not been adequately elucidated. State-of-the-art proteomics techniques are capable of identifying and quantifying this therapy-specific subproteome to enable the analysis of disease- or membrane-induced pathophysiologies. We demonstrate the feasibility of the deep proteomic characterization of the extracorporeal proteome adsorbed to HD-M. A shotgun proteomics

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… The enrichment analysis of the same proteins for their molecular function revealed the broad and diverse involvement of the proteins bound to hemodialyzer membranes, ranging from fibrinogen and RAGE receptor binding to phosphatidylcholine-sterol and peroxiredoxin activity and to haptoglobin and complement … Noticeable results were the most prominent terms in both categories being related to lipoproteins, as well as some overrepresented terms, such as RAGE receptor, fibrinogen and vesicle-related terms. …

Уменьшается объем клаустрома в множестве склерозов и прогнозов инвалидности.

ЦЕЛЬ: Клаустром представляет собой небольшую, тонкую структуру преимущественно серых веществ с широкой связью и загадочной функцией. О воздействии патологии клаустрома на множественный склероз (MS) известно мало. МЕТОДЫ: В этом исследовании была проведена оценка того, был ли сокращен объем клаустрома в НР и было ли сокращение связано с конкретными областями инвалидности. Мы сравнили влияние сокращения объема клауструма на неврологические расстройства с хорошо изученным таламусом. Данные, полученные из 15,793 Для проведения первичного анализа использовались участники исследования MS PATHS. Втор

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… In brief, each subject and visit contributed a 3D T1‐weighted MP‐RAGE and a 3D T2‐weighted FLAIR image. Both sequences were acquired with 1 mm [ 3 ] isotropic voxels with the same field of view. All imaging was performed on 3 T Siemens (Erlangen, Germany) scanners. Subjects in the John L. … FLAIR images (voxel size 1 × 1 × 3 mm) and MP‐RAGE (voxel size 1 × 1 × 1 mm) were acquired. Claustrum and Thalamus Segmentation Claustrum probability maps were generated using a deep learning segmentation tool applied to T1‐weighted images [ 16 ]. …

Neutrophil extracellular traps in homeostasis and disease.

Neutrophil extracellular traps (NETs), crucial in immune defense mechanisms, are renowned for their propensity to expel decondensed chromatin embedded with inflammatory proteins. Our comprehension of NETs in pathogen clearance, immune regulation and disease pathogenesis, has grown significantly in recent years. NETs are not only pivotal in the context of infections but also exhibit significant involvement in sterile inflammation. Evidence suggests that excessive accumulation of NETs can result in vessel occlusion, tissue damage, and prolonged inflammatory responses, thereby contributing to the

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… When activated, RAGE activates multiple intracellular signaling pathways and promotes the production of various inflammatory substances. HMGB1, by binding to RAGE, induces neutrophil activation and promotes the formation of NETs, a process that is dependent on the involvement of NADPH oxidase. … The disulfide HMGB1 has also been observed in venous thrombosis to promote pro-thrombotic NET formation mediated by RAGE. …

Peripheral Neuropathy During Concomitant Administration of Proteasome Inhibitors and Factor Xa Inhibitors: Identifying the Likelihood of Drug-Drug Interactions.

Backgrounds: Proteasome inhibitors (PI) cause toxic peripheral neuropathy (PN), which is one of the dose-limiting adverse events of these treatments. Recent preclinical studies find that factor Xa inhibitor (FXaI), rivaroxaban, promotes PN in animals receiving oxaliplatin. Cancer patients can receive combined therapy of PI and FXaI. This study aimed to identify and characterize the interaction signals for the concomitant use of PI and FXaI resulting in PN. Methods: Reports from the United States FDA Adverse Event Reporting System (FAERS) were extracted from the first quarter of 2004 to the fir

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… HMGB1 activates the receptor for advanced glycosylation end-product (RAGE) and other receptors, causing hyperalgesia/allodynia in animal models. … In particular, LMWH, another anticoagulant that preferentially inhibits RAGE but not HMGB1 accumulation, can prevent and reverse HMGB1-dependent pain, including CIPN, in rodents treated with paclitaxel ( Sekiguchi et al., 2018 ) or oxaliplatin ( Tsubota et al., 2019 ). …

New prognostic biomarkers and therapeutic effect of bevacizumab for patients with non-small-cell lung cancer.

BackgroundSeveral biomarkers have emerged as potential prognostic and predictive markers for non-small-cell lung cancer (NSCLC). Successful inhibition of angiogenesis with the antivascular endothelial growth factor antibody, bevacizumab, has improved the efficacy seen with standard cytotoxic therapy of NSCLC. However, despite such enhanced treatment strategies, the prognosis for patients with advanced NSCLC remains poor.Patients and methodsWe assessed potential biomarkers in 161 NSCLC patients and 42 control patients. Enzyme-linked immunosorbent assay methods were used to evaluate three biomar

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… crucial role in the cellular response to tissue damage. 62 HMGB1 expression is detectable in multiple immune and inflammatory diseases, 63 and HMGB1 protein is sequestered by thrombomodulin in vivo. 64 Moreover, HMGB1 stimulates toll-like receptor (TLR) and receptor for advanced glycation end products (RAGE … Activation of TLR or RAGE on endothelial cells or platelets stimulates release of PAI-1 and PDMP into the circulation and promotes vasculopathy. Therefore, the presence of HMGB1, PDMP, and PAI-1 could contribute to vascular complications such as thrombosis formation. …

Autophagic mechanisms in longevity intervention: role of natural active compounds.

The term 'autophagy' literally translates to 'self-eating' and alterations to autophagy have been identified as one of the several molecular changes that occur with aging in a variety of species. Autophagy and aging, have a complicated and multifaceted relationship that has recently come to light thanks to breakthroughs in our understanding of the various substrates of autophagy on tissue homoeostasis. Several studies have been conducted to reveal the relationship between autophagy and age-related diseases. The present review looks at a few new aspects of autophagy and speculates on how they m

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… 172 ) Tannins Corilagin Gastric cancer (SGC7901, BGC823) Autophagy induction Induces ROS (Ref. 173 ) Tannins Punicalagin Glioblastoma (U87-MG) Autophagy induction Increases AMPK/p27 (Ref. 174 ) Terpenoids Lucidone Pancreatic ductal adenocarcinoma (MIA Paca-2) Autophagy inhibition Inhibits the HMGB1/RAGE … Lucidone, a terpeneoid, inhibited autophagy via HMGB1/RAGE/PI3K/Akt signalling pathway in pancreatic cancer cells (Ref. 175 ). Celastrol induced autophagy by targeting AR/miR-101 and served as epigenetic regulator in prostate cancer cell lines (Ref. 176 ). …

Mechanisms of chemotherapy-induced behavioral toxicities.

While chemotherapeutic agents have yielded relative success in the treatment of cancer, patients are often plagued with unwanted and even debilitating side-effects from the treatment which can lead to dose reduction or even cessation of treatment. Common side effects (symptoms) of chemotherapy include (i) cognitive deficiencies such as problems with attention, memory and executive functioning; (ii) fatigue and motivational deficit; and (iii) neuropathy. These symptoms often develop during treatment but can remain even after cessation of chemotherapy, severely impacting long-term quality of lif

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… Extracellular HMGB1 can promote angiogenesis, stem cell migration, as well as neutrophil recruitment and subsequent pro-inflammatory immune responses via the activation of TLR2, TLR4, and RAGE. … Additionally, HMGB1 can also activate numerous immune cells including macrophages and dendritic cells via TLR and RAGE to stimulate the release of cytokines such as TNF-α, interleukin (IL)-1α, IL-1β, and IL-6 (Lotze and Tracey, 2005 ). …

Bortezomib-induced peripheral neuropathy: from molecular mechanisms to clinical management.

Bortezomib (BTZ) is a first-generation proteasome inhibitor that has shown significant efficacy in the treatment of multiple myeloma (MM), providing significant therapeutic benefits without severely compromising overall patient health. However, one of the most common and debilitating side effects associated with BTZ therapy is bortezomib-induced peripheral neuropathy (BIPN). This condition is the leading complication observed in patients undergoing BTZ treatment and has a profound impact on treatment regimens, often necessitating dose reductions or alterations in the dosing schedule. Despite t

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… Research indicates that BIPN may arise from the activation of the RAGE/STAT3 signaling pathway in the dorsal horn, which is driven by the accumulation of methylglyoxal. … Intrathecal metformin injection significantly reduced methylglyoxal levels and RAGE upregulation in the dorsal horn of the spinal cord in a rat model of BIPN, effectively blocking BTZ-induced central sensitization and mechanical pain abnormalities ( Wei et al., 2017 ). …

Капиллероскопия с капиллароскопией в диабетической ретинопатии: микровирусные озарения, клиническая ценность и проблемы с переводом - обзор повествования.

Диабетическая ретинопатия (DR) является одним из основных микроваскуловых осложнений сахарного диабета и одной из основных причин предотвратимой потери зрения. В настоящее время DR рассматривается как проявление системной диабетической микроангиопатии, а не изолированного окулярного расстройства. Оценка на основе сетчатки может не в полной мере отражать системное микроваскулярное бремя, особенно в тех случаях, когда доступ к специализированной сетчатке сетчатки ограничен. Капиллероскопия с капиллярным влагом (НКЦ) позволяет напрямую и неинвазивно визуализировать периферическую капиллярную морф

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… Several interconnected pathways are implicated: the AGEs–RAGE axis amplifies oxidative stress and impairs endothelial function ( 16 , 17 ); PKC activation modulates vascular permeability and enhances VEGF-mediated pro-angiogenic signaling ( 18 ); and the polyol pathway compromises antioxidant defenses … improvement; NS, Not significant; NVC, Nailfold videocapillaroscopy; NVU, Neurovascular unit; OCT, Optical coherence tomography; OCTA, Optical coherence tomography angiography; OR, Odds ratio; PDGF-BB, Platelet-derived growth factor BB; PDR, Proliferative diabetic retinopathy; PKC, Protein kinase C; RAGE …

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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… Antagonism of HMGB1 receptors, TLR4, receptor for advanced glycation end products (RAGE) and CXCR4, prevented the appearance of mechanical allodynia, whilst only RAGE was overexpressed in the DRG; no modifications of TLR4, CXCR4 and RAGE were observed in the sciatic nerve ( Tsubota et al., 2019 ). … As previously mentioned, HMGB1 can bind to different receptors: RAGE, CXCR4 and TLR4. …

Research progress in inducing immunogenic cell death of tumor cells.

Immunogenic cell death (ICD) is a regulated cell death (RCD) pathway. In response to physical and chemical signals, tumor cells activate specific signaling pathways that stimulate stress responses in the endoplasmic reticulum (ER) and expose damage-associated molecular patterns (DAMPs), which promote antitumor immune responses. As a result, the tumor microenvironment is altered, and many tumor cells are killed. The ICD response in tumor cells requires inducers. These inducers can be from different sources and contribute to the development of the ICD either indirectly or directly. The combinati

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… During the ICD response in tumor cells, HMGB1 is released extracellularly to bind to pattern recognition receptors (PRRs), including Toll-like receptors and receptors of advanced glycation end products (RAGE) ( 30 ). … Moreover, immune cells are recruited to exert a powerful antitumor immune effect by interacting with RAGE ( 32 ). …

Immune Dysfunction in Uremia 2020.

Cardiovascular disease and infections are major causes for the high incidence of morbidity and mortality of patients with chronic kidney disease. Both complications are directly or indirectly associated with disturbed functions or altered apoptotic rates of polymorphonuclear leukocytes, monocytes, lymphocytes, and dendritic cells. Normal responses of immune cells can be reduced, leading to infectious diseases or pre-activated/primed, giving rise to inflammation and subsequently to cardiovascular disease. This review summarizes the impact of kidney dysfunction on the immune system. Renal failur

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… AGEs exert their harmful effects by binding to their cell surface receptor, RAGE [ 227 ]. Compared to unmodified proteins, proteins modified with glucose in vitro increase PMNL chemotaxis and the stimulation of glucose uptake by PMNLs [ 228 ]. … AOPPs also interact with RAGE, suggesting that different oxidation products exert their biological effects via common signal transduction pathways [ 233 ]. As uremic toxins with pro-inflammatory effects, they activate the oxidative burst in PMNLs and monocytes [ 234 ]. …

PRMT inhibitor promotes SMN2 exon 7 inclusion and synergizes with nusinersen to rescue SMA mice.

Spinal muscular atrophy (SMA) is a leading genetic cause of infant mortality. The advent of approved treatments for this devastating condition has significantly changed SMA patients' life expectancy and quality of life. Nevertheless, these are not without limitations, and research efforts are underway to develop new approaches for improved and long-lasting benefits for patients. Protein arginine methyltransferases (PRMTs) are emerging as druggable epigenetic targets, with several small-molecule PRMT inhibitors already in clinical trials. From a screen of epigenetic molecules, we have identifie

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… Nat Biotechnol 33: 290–295 Piazzon N, Rage F, Schlotter F, Moine H, Branlant C, Massenet S (2008) In vitro and in cellulo evidences for association of the survival of motor neuron complex with the Fragile X mental retardation protein. … Nat Biotechnol 28: 1057–1068 Rage F, Boulisfane N, Rihan K, Neel H, Gostan T, Bertrand E, Bordonné R, Soret A (2013) Genome‐wide identification of mRNAs associated with the protein SMN whose depletion decreases their axonal localization. …

HMGB1 enhances chemotherapy resistance in multiple myeloma cells by activating the nuclear factor-κB pathway.

Chemotherapy resistance is a main obstacle in the clinical chemotherapeutic treatment of multiple myeloma (MM). High-mobility group box 1 (HMGB1) has been revealed to be associated with the sensitivity of MM cells to chemotherapy, but how HMGB1 regulates chemotherapy resistance in MM has yet to be fully elucidated. In the present study, the exact molecular mechanism underlying HMGB1-mediated drug resistance in MM was explored using three chemotherapy-resistant MM cells (RPMI8226/ADR, RPMI8226/BOR and RPMI8226/DEX) that were successfully established. Reverse transcription-quantitative polymeras

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… High mobility group box 1 promotes the epithelial-to-mesenchymal transition in prostate cancer PC3 cells via the RAGE/NF-κB signaling pathway. Int J Oncol. 2018;53:659–671. doi: 10.3892/ijo.2018.4420. 27. Livak KJ, Schmittgen TD. … Convergence and amplification of toll-like receptor (TLR) and receptor for advanced glycation end products (RAGE) signaling pathways via high mobility group B1 (HMGB1) Angiogenesis. 2008;11:91–99. doi: 10.1007/s10456-008-9093-5. 40. …

The Application of Aptamer and Research Progress in Liver Disease.

Aptamers, as a kind of small-molecule nucleic acid, have attracted much attention since their discovery. Compared with biological reagents such as antibodies, aptamers have the advantages of small molecular weight, low immunogenicity, low cost, and easy modification. At present, aptamers are mainly used in disease biomarker discovery, disease diagnosis, treatment, and targeted drug delivery vectors. In the process of screening and optimizing aptamers, it is found that there are still many problems need to be solved such as the design of the library, optimization of screening conditions, the tr

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… | RAGE | Melanoma liver metastasis | Inhibits tumor angiogenesis and inhibits melanoma growth and liver metastasis | Therapy | [ 115 ] Aptamers are Used in the Diagnosis and Therapy of Liver Cancer Cancer may not show symptoms in its early stages, which prevents timely diagnosis and treatment of cancer … RAGE-aptamer attenuates the growth and liver metastasis of malignant melanoma in nude mice. Molecular Medicine (Cambridge, Massachusetts) 2017;23:295–306. doi: 10.2119/molmed.2017.00099. 116. Zhang GQ, Zhong LP, Yang N, Zhao YX. …

Clinical characteristics and outcomes of patients on haemodialysis at Jimma medical center, Ethiopia: a 7-Year review.

BACKGROUND: Haemodialysis is the primary kidney replacement therapy modality in Africa. In Ethiopia, the number of patients undergoing Haemo … ients underwent Haemodialysis at Jimma Medical Center, with a predominance of males (69.1%). The average age of patients was 42.7 (± 12.8) years with 69.1% (95% CI: 57.5-79.1%) diagnosed with chronic kidney disease, while 30.9% (95% CI: 20.9-42.5%) had acute kidney injury. Among chronic kidney disease patients, common clinical features included nausea …

Semaglutide: a key medication for managing cardiovascular-kidney-metabolic syndrome.

Recent trials underscore the cardiovascular (CV), renal, and metabolic benefits of semaglutide in individuals with and without type 2 diabetes (T2D). In T2D, semaglutide enhances glycemic control, reduces major adverse CV events (MACE), and slows chronic kidney disease (CKD) progression. The SUSTAIN-6 trial demonstrated a 26% MACE reduction (HR 0.74; 95% CI: 0.58-0.95; p = 0.02) in high CV-risk patients with T2D using semaglutide (0.5 or 1.0 mg weekly). Similarly, the FLOW trial showed a 24% reduction in major kidney disease events (HR 0.76; 95% CI: 0.66-0.88; p = 0.002) with weekly 1.0 mg sem

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… Preclinical studies show that receptor for advanced glycation end products (RAGE) deletion reduces inflammation, and RAGE knockout mice are protected against nephropathy [ 19 , 20 ]. AGEs and ROS also drive endothelial dysfunction, a key factor in diabetic vascular complications [ 14 , 17 , 18 ]. … Transactivation of RAGE mediates angiotensin-induced inflammation and atherogenesis. J Clin Invest. 2019;129(1):406–421. doi: 10.1172/JCI99987 21. Whaley-Connell A, Sowers JR. Oxidative stress in the cardiorenal metabolic syndrome. …

The Impact of Ketogenic Nutrition on Obesity and Metabolic Health: Mechanisms and Clinical Implications.

The ketogenic diet (KD) has recently gained increasing popularity. This high-fat, adequate-protein, and carbohydrate-poor eating pattern leads to nutritional ketosis. The KD has long been known for its antidiabetic and antiepileptic effects and has been used therapeutically in these contexts. Recently, the KD, due to its effectiveness in inducing weight loss, has also been proposed as a possible approach to treat obesity. Likewise, a KD is currently explored as a supporting element in the treatment of obesity-associated metabolic disorders and certain forms of cancer. Here, we discuss the meta

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… In a cohort of 37 patients with OA who underwent fasting for 8 days, a significant, but non-sustained, reduction in RAGE levels in serum but not of AGEs was found; however, no correlation with improvement in clinical endpoints of OA was found. 129 Low-carbohydrate diets have been reported to provide … AGE-RAGE interaction does not explain the clinical improvements after therapeutic fasting in osteoarthritis. Complement Med Res. 2018;25:167-172. 10.1159/000486237 130. Strath LJ, Jones CD, Philip George A, et al. …

Исследование безопасности фамфридина у пациентов с различными стадиями множественного склероза.

Fampridine является единственным лекарственным средством, утвержденным Администрацией США по контролю за продуктами питания и лекарствами для лиц с множественным склерозом (MS) в целях улучшения их передвижения и продемонстрировал клинически существенное улучшение функции похода в группе пациентов с повышенным уровнем инвалидности (ESDSS) из группы MS. 4 в адрес 7. Тем не менее, согласно сообщениям, это лекарство имеет некоторые неблагоприятные последствия (АЭ), такие, как припадок из-за его фармакологических свойств. Цель этого исследования заключалась в оценке распространенности побочных эфф

Нейтрофильные внеклеточные ловушки в расстройствах центральной нервной системы: механизмы, последствия и новые перспективы.

Нейтрофильные внеклеточные ловушки (НЕТ) в качестве важнейшего защитного механизма нейтрофилов в последние годы привлекли все большее внимание к их роли в расстройствах центральной нервной системы (КНС). В настоящем обзоре содержится исчерпывающая краткая информация об основных характеристиках и механизмах формирования ННО, а также освещаются последние результаты исследований, касающихся их участия в различных заболеваниях НКЦ. Обсуждаются конкретные механистические идеи, в том числе то, как НЕТ усугубляют ишемический инсульт в результате иммунотромбоза, способствуют нарушению кровеносных барь

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… Moreover, their findings indicate that NETs generated by neutrophils infiltrating tumors facilitate communication between glioma development and the tumor microenvironment by modulating the HMGB1/RAGE/IL-8 pathway ( 52 ). …