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Close interactions between lncRNAs, lipid metabolism and ferroptosis in cancer.

Abnormal lipid metabolism including synthesis, uptake, modification, degradation and transport has been considered a hallmark of malignant tumors and contributes to the supply of substances and energy for rapid cell growth. Meanwhile, abnormal lipid metabolism is also associated with lipid peroxidation, which plays an important role in a newly discovered type of regulated cell death termed ferroptosis. Long noncoding RNAs (lncRNAs) have been proven to be associated with the occurrence and progression of cancer. Growing evidence indicates that lncRNAs are key regulators of abnormal lipid metabo

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… When there is too much FA, most of the FA can be connected to the glycerol backbone to form TG, which is then stored in cytoplasmic lipid droplets (LDs) 145 . This storage itself is not disease-causing, but TG, as a substance for storing FA, can release FA at any time. … LncRNAs regulate the synthesis of triglyceride First, FA is activated into fatty acyl-CoA (FA-CoA), and FA-CoA forms lysophosphatidic acid (LPA) under the action of glycerol 3-phosphate acyltransferase (GPAT). …

Novel A Автоматизированная химилюминесцентная иммуномасса для обнаружения самоорганических организмов против аквапорина-4 в нейромиэлита Оптика Спектрума.

Фон/цели: Нейромиелитное расстройство спектра (NMOSD) является аутоиммунным неврологическим заболеванием, которое в первую очередь влияет на зрительный нерв и спинной мозг. Согласно существующим международным согласованным руководящим принципам для НМОСР, подтверждение наличия аквапорина-4 иммуноглобулина G антитела (AQP4-IgG) является одним из наиболее важных диагностических критериев, поскольку AQP4-IgG является важным диагностическим биомаркером НМОСД. В настоящее время имеется несколько анализов для обнаружения AQP4-IgG, включая клеточные анализы (CBA) и иммуносорбенты, связанные с фермент

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… Fractions containing the antibodies were dialyzed against 50% ( v / v ) glycerol/phosphate-buffered saline. Purified antibodies were checked by SDS-PAGE and were quantified using a Nanodrop instrument (Thermo Fisher Scientific, Waltham, MA, USA). They were stored below −20 °C until use. 2.4. …

Zoledronic acid enhances lipopolysaccharide-stimulated proinflammatory reactions through controlled expression of SOCS1 in macrophages.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious side effect of nitrogen-containing bisphosphonate (NBP) use. Many studies have shown that BRONJ is limited to the jawbone and does not occur in the other bones. We hypothesized that BRONJ is related to local bacterial iections and involves the innate immune system. To examine the relationship between BRONJ and innate immunity, we examined the effects of NBPs on macrophages, one of the important cell types in innate immunity. The expression of toll-like receptor-4 (TLR4) in cells after pretreatment with zoledronic acid (ZOL) d

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… Samples containing equal protein were mixed with 5× sample buffer (20% glycerol, 10% 0-mercaptoethanol, 6% sodium dodecyl sulfate, and 125mM Tris-HCl [pH 6.8]). …

Sclerostin induced tumor growth, bone metastasis and osteolysis in breast cancer.

Breast cancer is the second leading cause of cancer-related deaths among women worldwide. Many patients suffer from bone metastasis. Sclerostin, a key regulator of normal bone remodeling, is critically involved in osteolytic bone diseases. However, its role in breast cancer bone metastasis remains unknown. Here, we found that sclerostin was overexpressed in breast cancer tumor tissues and cell lines. Inhibition of sclerostin by antibody (Scl-Ab) significantly reduced migration and invasion of MDA-MB-231 and MCF-7 cells in a time- and dose-dependent manner. In xenograft model, sclerostin inhibi

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… Western blot analysis Western blot analysis was performed using protein extracted from cell lysates or supernatant culture medium, which were dissolved in loading buffer (5× solution of 50% glycerol, 10% sodium dodecyl sulfate, 5% β-mercaptoethanol, 0.5% bromophenol blue, and 250 mM Tris-HCl pH 6.8) …

Selective molecular inhibition of the HDAC6 ZnF-UBP binding domain impairs multiple myeloma cell function.

Multiple myeloma is a plasma cell malignancy with a poor prognosis despite the recent development of new therapeutic options. Histone deacetylase 6 (HDAC6) is overexpressed in multiple myeloma cells and may be involved in the acquisition of resistance to conventional anti-proteasome treatments. In addition to displaying a deacetylase catalytic activity, HDAC6 plays an essential role in the regulation of autophagy and cell death by recognizing ubiquitinated motifs from misfolded proteins through its C-terminal ZnF-UBP binding domain. These defective proteins are sent to the aggresome to facilit

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… The supernatant was discarded, and the pellet was resuspended in buffer (20 mM Tris-HCl (pH 8), 500 mM NaCl, 20 mM imidazole (pH 8), 10% glycerol, 10 mM β-mercaptoethanol, 1 mM PMSF). … Protein samples (30 μg) were mixed with loading buffer (50 mM Tris pH 6.8, 6.5% glycerol, 1% sodium dodecyl sulfate, 50 mM dithiothreitol, 0.012% bromophenol blue) and heated to 95 °C for 5 min. …

Fasting-Mimicking Diet Is Safe and Reshapes Metabolism and Antitumor Immunity in Patients with Cancer.

In tumor-bearing mice, cyclic fasting or fasting-mimicking diets (FMD) enhance the activity of antineoplastic treatments by modulating systemic metabolism and boosting antitumor immunity. Here we conducted a clinical trial to investigate the safety and biological effects of cyclic, five-day FMD in combination with standard antitumor therapies. In 101 patients, the FMD was safe, feasible, and resulted in a consistent decrease of blood glucose and growth factor concentration, thus recapitulating metabolic changes that mediate fasting/FMD anticancer effects in preclinical experiments. Integrated

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… One major issue related to the use of fasting/FMD in patients with cancer is the risk of causing progressive weight loss by inducing or accelerating the release of amino acids, glycerol, and fatty acids from skeletal muscles and adipose tissue ( 28 ). … Because of the complexity of homeostatic mechanisms regulating systemic metabolism in humans, such as glycerol- or amino acid–sustained neoglucogenesis, we expected less significant metabolic changes in patients than in mice ( 7, 30–32 ). …

Microorganisms Associated with the Marine Sponge Scopalina hapalia: A Reservoir of Bioactive Molecules to Slow Down the Aging Process.

Aging research aims at developing therapies that delay normal aging processes and some related pathologies. Recently, many compounds and extracts from natural products have been shown to slow aging and/or extend lifespan. Marine sponges and their associated microorganisms have been found to produce a wide variety of bioactive secondary metabolites; however, those from the Southwest of the Indian Ocean are much less studied, especially regarding anti-aging activities. In this study, the microbial diversity of the marine sponge Scopalina hapalia was investigated by metagenomic analysis. Twenty-s

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… For long-term strain collection, the microorganisms were stored at −80 °C in a cryoprotectant medium (skimmed milk (Régilait, Macon, France) 10% ( w / v ), glycerol (Carlo Erba, Val de Reuil, France) 10% ( v / v ) and sea salts 33 g/L). … On arrival, the strains were cultivated on malt extract agar (MEA) and dichloran 18% glycerol agar (DG18). DNA was extracted from one MEA plate after an incubation period of three days in the dark at 25 °C, using the Qiagen DNeasy Ultraclean™ Microbial DNA Isolation Kit (Qiagen, Germany). …

Bioabsorbable polymers in cancer therapy: latest developments.

Cancer is a devastating disease, being responsible for 13 % of all deaths worldwide. One of the main challenges in treating cancer concerns the fact that anti-cancer drugs are not highly specific for the cancer cells and the "death" of healthy cells in the course of chemotherapy treatment is inevitable. In this sense, the use of drug delivery systems (DDS) can be seen as a powerful tool to minimize or overcome this very important issue. DDS can be designed to target specific tissues in order to mitigate side effects. Bioabsorbable polymers, due to their inherent characteristics, and because th

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… Yohe et al. [ 123 ] prepared 3D superhydrophobic electrospun meshes based on PCL and the hydrophobic polymer dopant poly(glycerol monostearate- co -ε-caprolactone) (PGC-C18) and tested their potential as local DDS for colorectal cancer cells, using CPT-11 and SN-18 as model drugs. … hydroxyhexanoate) poly(2-ethylbutoxy phospholane)- b -poly(2-butynylphospholane)- g -poly(ethylene glycol) poly(ɛ-caprolactone) poly(D-lactic acid) poly(D,L-lactic acid) poly(ethyl ethylene phosphate) poly(ethylene glycol) poly(ethylene oxide)- b -poly(3-hydroxybutyrate)- b -poly(ethylene oxide) poly(glycerol …

Unc-51 like kinase 3 (ULK3) contributes to autophagy and cell survival in multiple myeloma.

Despite effective therapies such as proteasome inhibitors, multiple myeloma (MM) patients relapse with refractory disease. Analysis of RNA sequencing data from CD138 + MM patient cells (n = 813) across disease stages identifies an autophagy gene signature. Particularly elevated ULK3 expression is strongly associated with disease progression. Functional studies reveal that ULK3 supports MM cell survival via the ULK-ATG13-FIP200 complex. We generate small-molecule kinase inhibitors (SG3-014/MA9-060) exhibiting nanomolar potency against ULK3, with binding confirmed by co-crystallization. While ex

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… Cell pellets were resuspended in lysis buffer containing 50 mM HEPES (pH 7.4), 500 mM NaCl, 20 mM imidazole, 0.5 mM tris(2-carboxyethyl) phosphine (TCEP), 10 µM MnCl₂, 5% glycerol, 0.1% Triton X-100, and EDTA-free protease inhibitor cocktail (1 tablet per 50 mL; Roche). … Clarified lysate was applied to Ni-NTA Superflow resin (Qiagen), and the fusion protein was eluted using a linear imidazole gradient in buffer containing 50 mM HEPES (pH 7.4), 500 mM NaCl, 0.5 mM TCEP and 5% glycerol. …

Causal relationships between immune cells, inflammatory factors, serum metabolites, and hepatic cancer: A two-sample Mendelian randomization study.

BackgroundObservational studies and clinical trials suggest associations between immune cells, inflammatory factors, serum metabolites, and hepatic cancer. However, the causal relationships between these factors and hepatic cancer remain to be established.ObjectiveTo explore the causal relationships between immune cells, inflammatory factors, serum metabolites, and hepatic cancer.MethodsThis study employed comprehensive two-sample Mendelian randomization (MR) utilizing publicly available genetic data (GWAS) to analyze causal relationships between 731 immune cell traits, 91 inflammatory factors

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… Additionally, 2-stearoyl-GPE (18:0) levels (GCST90199928), 3beta-hydroxy-5-cholestenoate levels (GCST90200014), and Benzoate to oleoyl-linoleoyl-glycerol (18:1 to 18:2) [2] ratio (GCST90200987) were also identified as risk factors for hepatic cancer. …

Efficacy of phosphodiesterase type 5 inhibitors in univentricular congenital heart disease: the SV-INHIBITION study design.

AIMS: In univentricular hearts, selective lung vasodilators such as phosphodiesterase type 5 (PDE5) inhibitors would decrease pulmonary resistance and improve exercise tolerance. However, the level of evidence for the use of PDE5 inhibitors in patients with a single ventricle (SV) remains limited. We present the SV-INHIBITION study rationale, design, and methods. METHODS AND RESULTS: The SV-INHIBITION trial is a nationwide multicentre, randomized, double blind, placebo-controlled, Phase III study, aiming to evaluate the efficacy of sildenafil on the ventilatory efficiency during exercise, in

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… hepatic insufficiency (Child‐Pugh C class) • Hypersensitivity to the active substance or to any of the excipients of the tablet: microcrystalline cellulose, calcium hydrogen phosphate anhydrous, croscarmellose sodium, stearate of magnesium, hypromellose, titanium dioxide (E171), monohydrate lactose, glycerol …

TrkB promotes laryngeal cancer metastasis via activation PI3K/AKT pathway.

ObjectivesThe aim of our study was to investigate the role of TrkB pathway in tumor occurrence and development for in order to provide theoretical basis to laryngeal cancer therapy.Materials and methodsBiological characteristics of the cells were studied by migration tests and colony forming assay. Gene and protein expression analysis was performed by RT-PCR or western blot. in vivo experiments were conducted in syngeneic BALB/c mice.ResultsSignificant changes in protein and gene expression, including higher expression level of TrkB, were found in cells and laryngeal cancer specimens. we demon

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… The lysis buffer with pH 6.8 contained 10% glycerol, 5% 2-mercaptoethanol, 2% sodium dodecyl sulfate (SDS), 62.5 mmol/L Tris-HCl. The SDS–PAGE analysis was performed and membranes were incubated overnight at 4°C with antibodies directed against the indicated proteins. …

Dexamethasone and lenalidomide have distinct functional effects on erythropoiesis.

Corticosteroids and lenalidomide decrease red blood cell transfusion dependence in patients with Diamond-Blackfan anemia (DBA) and myelodysplastic syndrome (MDS), respectively. We explored the effects of dexamethasone and lenalidomide, individually and in combination, on the differentiation of primary human bone marrow progenitor cells in vitro. Both agents promote erythropoiesis, increasing the absolute number of erythroid cells produced from normal CD34(+) cells and from CD34(+) cells with the types of ribosome dysfunction found in DBA and del(5q) MDS. However, the drugs had distinct effects

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… group, CcEe antigens | Dex + Len | Rh antigens appear early during erythropoietic differentiation 45 JAK2 | Janus kinase 2 (a protein tyrosine kinase) | Dex + Len | Essential role in erythropoiesis, including response to erythropoietin 46 AQP3 | Aquaporin 3 (GIL blood group) | Dex + Len | Water and glycerol …

Adult-Onset Hyperammonemia: Case Report and Review of Literature.

INTRODUCTION: Hyperammonemia is a life-threatening condition most associated with liver disease, though non-cirrhotic causes are increasingly recognized. CASE PRESENTATION: We report an 18-year-old female presenting with 1 week of progressive confusion, abdominal pain, and nausea. Initial evaluation showed normal routine laboratories but markedly elevated ammonia and respiratory alkalosis. She rapidly deteriorated, requiring intubation and intensive care. Ammonia peaked at 795 µg/dL and improved rapidly after urgent venous hemofiltration and medical therapy, with full neurological recovery by

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… Intravenous nitrogen-scavenging therapy with sodium benzoate, sodium phenylbutyrate, and glycerol triphenyl butyrate promotes nitrogen ( Table 2 ). Therapy continues until HA resolves and enteral nutrition resumes. …

Микробиомы воспаления имеют функциональную патогенность, предсказанную реактивным белком C.

Мы изучаем специфические по болезням и перекрестные заболевания человеческого кишечного микробиома путем колонизации мышей, свободных от микробов, подверженных риску возбудителя артрита, колита или нейроинфламмы, с более чем 100 фекальными микробиомами человека от лиц с ревматоидным артритом, анкилосирующим спондилитом, множественным склерозом, язвительным колитом, болезнью Крона или раком цвета. Мы находим типичные воспалительные фенотипы, приводимые в действие микробиомами у лиц с кишечным воспалением или подстрекательским артритом, а также различные функции, характерные для микробиомов, у п

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… Samples were cryopreserved at −80°C at approximately 2.5 mg/mL in LYBHI media supplemented with 15% glycerol. …

Высоко избирательная и верзольная платформа для визуализации липаса Моноацилглицерол.

Monoacylglycerol Lipase (MAGL) — ключевой фермент для прекращения сигнала в эндоканнабиноидной системе (ECS). Ингибиция MAGL приводит к косвенной активации каннабиноидных рецепторов, что дает уникальные преимущества для лечения, например, множественных склерозов, эпилепсии и других неврологических расстройств. Технологии молекулярной съемки являются ценными инструментами, позволяющими преодолеть нынешнее плохое понимание распределения и роли MAGL в пато- и физиологических процессах в рамках сигнала ECS. В этой связи мы представляем информацию о проектировании, синтезе и подтверждении высокосел…

A novel alkaloid compound, DCZ0358, exerts significant antitumor activity in bortezomib-resistant multiple myeloma cells through inhibition of JAK2/STAT3 pathway.

Multiple myeloma (MM), the second most common haematological malignancy, is currently incurable because patients often develop multiple drug resistance and experience subsequent relapse of the disease. This study aims to identify a potential therapeutic agent that can counter bortezomib (BTZ) resistance in MM. DCZ0358, a novel alkaloid compound, is found to exert potent cytotoxic effects against BTZ-resistant MM cells in vivo and in vitro. The anti-myeloma activity of DCZ0358 is associated with inhibition of cell proliferation, promotion of cell apoptosis via caspase-mediated apoptotic pathway

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… Western blot analysis BTZ-resistant cells (2×10 5 cells/mL) were treated with various concentrations of DCZ0358 and lysed with lysis buffer (100 mM Tris-HCl, pH 6.8, 4% SDS, and 20% glycerol) to extract proteins. …

Direct phenotypic conversion of human fibroblasts into functional osteoblasts triggered by a blockade of the transforming growth factor-β signal.

A procedure to generate functional osteoblasts from human somatic cells may pave the way to a novel and effective transplantation therapy in bone disorders. Here, we report that human fibroblasts were induced to show osteoblast phenotypes by culturing with ALK5 i II, which is a specific inhibitor for activin-like kinase 5 (ALK5) (tumor growth factor-β receptor 1 (TGF-β R1)). Cells cultured with ALK5 i II expressed osteoblast-specific genes and massively produced calcified bone matrix, similar to the osteoblasts induced from mesenchymal stem cells (MSC-OBs). Treatment with vitamin D3 in additio

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… Osteogenic medium consisted of the complete medium supplemented with 50 μg/mL ascorbic acid, 10 mM β-glycerol phosphate, and 100 nM dexamethasone. Cell culture Fibroblasts were cultured in the complete medium, which was replaced by fresh one every 3 to 4 days. …

Enzimatic Paradox of Yeast Arginil-tRNA Synthetase: Исключительная передача Аргинина, контролируемая гибким механизмом признания tRNA.

Детерминанты идентичности необходимы для точного признания переноса РНК синтетиками аминоачил-тРНА. На сегодняшний день аргининские детерминанты в дрожжах сачаромице были выявлены исключительно in vitro и только на ограниченном числе изоприятцев trNA Arginin. В нынешнем исследовании мы выступаем за полный клеточный подход и расширяем исследования аргининских детерминант до всех four TRNA Arg изо-приемники. В более конкретном плане эта работа позволяет проанализировать актуальность нуклеотидов ТРНА на месте. 20, 35 и 36 в реакции дрожжей на аргинилацию. Мы построили 21 мутантов мутагенезом, упр

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… Complexes were formed in 10 μl of binding buffer containing 25 mM Tris-HCl, pH 7.5, 75 mM KCl, 10 mM MgCl 2 , 25% glycerol and separated at room temperature for 120 min at 120V on native 6% (37.5:1, acrylamide:bisacrylamide) gels (200 x 200 x 1.5 mm 3 ). …

Coming of Age for Autotaxin and Lysophosphatidate Signaling: Clinical Applications for Preventing, Detecting and Targeting Tumor-Promoting Inflammation.

A quarter-century after the discovery of autotaxin in cell culture, the autotaxin-lysophosphatidate (LPA)-lipid phosphate phosphatase axis is now a promising clinical target for treating chronic inflammatory conditions, mitigating fibrosis progression, and improving the efficacy of existing cancer chemotherapies and radiotherapy. Nearly half of the literature on this axis has been published during the last five years. In cancer biology, LPA signaling is increasingly being recognized as a central mediator of the progression of chronic inflammation in the establishment of a tumor microenvironmen

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… Overview of LPA Signaling and Its Importance in Reproduction and Embryonic Development As the simplest bioactive glycerolphospholipid, LPA contains a glycerol backbone with a phosphate head group, and an acyl chain (usually unsaturated) at the sn-1 (or sn-2) position ( Figure 2 ). … This suggests that glycerol-lysophospholipids other than LPA might be involved in pathogenesis of cancer directly or through being converted into LPA [ 156 ]. Advances in the LPA field have also been made in gynecological cancers. …