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Необычная реакция профилей белков HERV-W в множестве склерозов: потенциальные биомаркеры для развития заболеваний.

ВВЕДЕНИЕ: Протеины конверта syncytin-1 и fHERV-W из эндогенной ретровирусной семьи человека "W" (HERV-W) были определены в качестве потенциальных факторов риска при множественном склерозе (MS). Цель этого исследования заключается в оценке как юморальной, так и клеточной иммунной реакции на антигенные пептиды, получаемые из этих белков, в различных клинических формах и фазах МУ. МЕТОДЫ: Косвенный анализ иммуносорбента, связанного с ферментом (ELISA), использовался для измерения ответов на иммуноглобулин G (IgG) syncytin-1env 486-500 и fHERV-Wenv 486-504 Пептиды у пациентов с склерозом. Дискрими

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… During the last 6 hours of culture, brefeldin A (BFA) (10 µg/ml) and monensin (0.7 µg/ml) (BD Biosciences, San Diego, CA, USA) were added. After incubation, cell cultures were washed with saline buffer (PBS) and centrifugated at 300 x g for 5 min at RT, discarding the supernatant. …

Выражение Brd4 в CD4 T клеток и в микроглии поощряет нейроинфламмацию в экспериментальном аутоиммунном энцефаломиелите.

Микроглии являются постоянными врожденными иммунными клетками центральной нервной системы (СНС), которые обеспечивают антимикробную защиту, но также способствуют нейроинфламмации. BRD4 — читатель хроматинов, связывающий себя с ацетилированными гистонами и направляющий транскрипцию множества генов. Однако неизвестно, регулирует ли и каким образом БРД4 функцию микроглии. Мы рассмотрели роль микроглии и BRD4 в нейро-воспалительном заболевании, экспериментальном аутоиммунном энцефаломиелите (EAE), модели мыши для множественных склерозов. Ранее сообщалось, что в EAE при первоначальной активации Т к

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… Prior to staining aliquots of splenocytes and lymph node cells (1 × 10 6 ) and neural mononuclear cells (5 × 10 4 ) were restimulated using PMA (50 ng/ml) and ionomycin (1 µg/ml) with 1 µl/ml Monensin at 37 0 C for 6 h. …

The TGF-β/SMAD pathway is an important mechanism for NK cell immune evasion in childhood B-acute lymphoblastic leukemia.

Natural killer (NK) cells are key components of the innate immune system, providing potent antitumor immunity. Here, we show that the tumor growth factor-β (TGF-β)/SMAD signaling pathway is an important mechanism for NK cell immune evasion in childhood B-acute lymphoblastic leukemia (ALL). We characterized NK cells in 50 consecutive children with B-ALL at diagnosis, end induction and during maintenance therapy compared with age-matched controls. ALL-NK cells at diagnosis had an inhibitory phenotype associated with impaired function, most notably interferon-γ production and cytotoxicity. By mai

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… CD107a antibody, monensin (BD GolgiStop) and BFA (Brefeldin A, Sigma, UK) were added to cultures at the start of incubation as previously published.( 15 ) Cells were stained with CD56 and CD3 mAb (Fisher Scientific), fixed/permeabilized (BD Biosciences), followed by intracellular cytokine staining with …

Unraveling the Anti-Cancer Mechanisms of Antibiotics: Current Insights, Controversies, and Future Perspectives.

Cancer persists as a significant global health challenge, claiming millions of lives annually despite remarkable strides in therapeutic innovation. Challenges such as drug resistance, toxicity, and suboptimal efficacy underscore the need for novel treatment paradigms. In this context, the repurposing of antibiotics as anti-cancer agents has emerged as an attractive prospect for investigation. Diverse classes of antibiotics have exhibited promising anti-cancer properties in both in vitro and in vivo studies. These mechanisms include the induction of apoptosis and cell cycle arrest, generation o

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… Monensin, a polyether antibiotic primarily used in veterinary medicine, exhibited anti-cancer properties when combined with erlotinib for the treatment of triple-negative breast cancer (TNBC) cells. … Combination of Monensin and Erlotinib Synergistically Inhibited the Growth and Cancer Stem Cell Properties of Triple-Negative Breast Cancer by Simultaneously Inhibiting EGFR and PI3K Signaling Pathways. Breast Cancer Res. Treat. 2024;207:435–451. doi: 10.1007/s10549-024-07374-y. 120. …

Magnetic Resonance Imaging Findings in 13 Neurologic Pot-Bellied Pigs.

This study reports the magnetic resonance imaging (MRI) findings in 13 pot-bellied pigs presented to our institution with neurological deficits. Nine pigs had abnormal MRI findings (7 with spinal cord localization and 2 with brain localization), with three of them having histopathological confirmation of the diagnoses. MRI diagnoses included a myopathy suspected to be secondary to Erysipelothrix rhusiopathiae, a round cell neoplasia involving the vertebral canal, myelomalacia, a cervical cyst like extradural lesion, pelvic fracture with secondary cauda equina involvement, two cases of fibrocar

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… Other common causes of muscle disease in this species include metabolic causes such as vitamin E and/or selenium deficiency, trauma, bacterial infections ( Actinobacillus suis, Clostridium sp.), Porcine Stress syndrome, Gossypol or Monensin toxicities, or parasitic myopathies ( Trichinella, Taenia ) …

Преодоление сопротивления CD44-overexpressing миэлома через комбинированную терапию с клетками ATRA, борцезомиба и NK.

CD44 — гликпротеин, часто переоцениваемый раком и связанный с плохим прогнозом. Мы проанализировали прогнозируемую значимость CD44 в перевыражении в миеломе (MM) и изучили терапевтическую эффективность сочетания естественной клеточной терапии убийцы (NK) с транс-ретиновой кислотой (ATRA) и борцезомибом (Bor) против CD44-overexpressing Мм. Для оценки результатов выживаемости по отношению к выражению CD44 были проанализированы клинические данные из базы данных CoMMpass. Ячейки NK были расширены за счет здоровых доноров с использованием K562-OX40L-mbIL-18/21 кормовые клетки, дополненные интерлейк

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… After 1 h, Monensin (BD Biosciences, San Jose, CA, USA) was added to the wells. Following a total of 4 h incubation, the cells were stained with antibodies against CD3 and CD56 for 20 min and analyzed on a BD FACSCalibur flow cytometer, collecting 10,000 events per sample. …

Role of autophagy in cholangiocarcinoma: An autophagy-based treatment strategy.

Cholangiocarcinomas (CCAs) are diverse biliary epithelial tumours involving the intrahepatic, perihilar and distal parts of the biliary tree. The three entirely variable entities have distinct epidemiology, molecular characteristics, prognosis and strategy for clinical management. However, many cholangiocarcinoma tumor-cells appear to be resistant to current chemotherapeutic agents. The role of autophagy and the therapeutic value of autophagy-based therapy are largely unknown in CCA. The multistep nature of autophagy offers a plethora of regulation points, which are prone to be deregulated and

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… Hydroxy-chloroquine (HCQ) | Autophagosome-lysosome fusion Clomipramine | Alter acidification of lysosomes Verteporfin | Alter acidification of lysosomes Paclitaxel | Microtubule stabilizer- inhibit phosphorylation of VPS34 at T159 Spain-1 | Inhibits the activity of ubiquitin-specific peptidases, USP10 and USP13 Monensin …

A probiotic approach identifies a Treg-centred immunoregulation via modulation of gut microbiota metabolites in people with multiple sclerosis and healthy individuals.

BACKGROUND: Modulation of the gut microbiota composition has been suggested as a potential disease modifying therapy in immune-mediated diseases such as multiple sclerosis (MS). However, a conclusive mechanism linking gut microbiota modulation to peripheral immune responses has remained elusive so far. METHODS: In this exploratory cohort study, people with MS (pwMS) and healthy controls (HC) supplemented a lactobacilli-rich probiotic for two or six weeks and were additionally investigated six weeks after the last intake. Immune cell phenotyping was performed in blood samples, complemented by

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… Intracellular cytokine staining and analysis 1 × 10 6 freshly isolated PBMCs were stimulated with ionomycin (0.75 mg/mL in DMSO, Sigma–Aldrich) and PMA (β = 1 mg/mL in R10, Sigma–Aldrich) together with Golgi-Stop Solution (containing Monensin, BD Biosciences) for 3 h at 37 °C. …

GZMK-expressing CD8+ T cells promote recurrent airway inflammatory diseases.

Inflammatory diseases are often chronic and recurrent, and current treatments do not typically remove underlying disease drivers1. T cells participate in a wide range of inflammatory diseases such as psoriasis2, Crohn's disease3, oesophagitis4 and multiple sclerosis5,6, and clonally expanded antigen-specific T cells may contribute to disease chronicity and recurrence, in part by forming persistent pathogenic memory. Chronic rhinosinusitis and asthma are inflammatory airway diseases that often present as comorbidities7. Chronic rhinosinusitis affects more than 10% of the general population8. Am

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… Subsequently, the cells were stimulated by either plate-bound anti-CD3 (9 μg ml −1 , clone OKT3) and anti-CD28 (9 μg ml −1 , clone CD28.2) antibodies or PMA (50 ng ml −1 ) and ionomycin (1 μg ml −1 ) for 4 h in the presence of the FITC-anti-LAMP1 antibodies (clone H4A3, BioLegend), and monensin (5 μΜ …

TH1-позиция наивной CD4-T субпопуляции клеток отражает антиопухоль и аутоиммунную болезнь.

Наив CD4 T клетки традиционно рассматриваются как тщеславное, однородное, отдыхающее население, но возникающие данные свидетельствуют об их неоднородности, которая может иметь решающее значение для понимания контекста заболеваний и терапевтических последствий. В этом исследовании мы идентифицируем отдельные подгруппы как в муринных, так и в наивных наивных наивных CD4 T клеток с помощью одноклеточных, РНК-секва (scRNA-seq), с особым акцентом на подгруппе, которая выражает сверхвысокий уровень интерлейкина-7 рецептора (IL-7Rsup-hi), наряду с CD97, IL-18R и LI6C. Эта подгруппа, отсутствующая в т

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… For further intracellular cytokine staining, cultured cells were re-stimulated by PMA (P-1585; Sigma, 40 ng/ml) and ionomycin (I-0634; Sigma, 0.8μg/ml) in the precence of monensin (51-2092kz; BD Bioscience). …

Targeting Reactive Oxygen Species Capacity of Tumor Cells with Repurposed Drug as an Anticancer Therapy.

Accumulating evidence shows that elevated levels of reactive oxygen species (ROS) are associated with cancer initiation, growth, and response to therapies. As concentrations increase, ROS influence cancer development in a paradoxical way, either triggering tumorigenesis and supporting the proliferation of cancer cells at moderate levels of ROS or causing cancer cell death at high levels of ROS. Thus, ROS can be considered an attractive target for therapy of cancer and two apparently contradictory but virtually complementary therapeutic strategies for the regulation of ROS to treat cancer. Desp

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… Doxycycline, salinomycin, monensin and ivermectin repositioned as cancer drugs Bioorganic & Medicinal Chemistry Letters 2019 29 13 1549 1554 10.1016/j.bmcl.2019.04.045 2-s2.0-85064895735 31054863 121 Tan Q. Yan X. Song L. …

Organelle-oriented nanomedicines in tumor therapy: Targeting, escaping, or collaborating?

Precise tumor therapy is essential for improving treatment specificity, enhancing efficacy, and minimizing side effects. Targeting organelles is a key strategy for achieving this goal and is a frontier research area attracting a considerable amount of attention. The concept of organelle targeting has a significant effect on the structural design of the nanodrugs employed. Most notably, the intricate interactions among different organelles in a tumor cell essentially create a unified system. Unfortunately, this aspect might have been somewhat overlooked when existing organelle-targeting nanodru

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… These include chondroitin sulfate (CS), retinoic acid (RA), six-cysteine (C 6 ) peptide, monensin, etc . ( Fig. 11 b) [ 231 , 232 ]. …

Mechanisms Behind the Pharmacological Application of Biochanin-A: A review.

This review was aimed at summarizing the cellular and molecular mechanisms behind the various pharmacological actions of biochanin-A. Many studies have been reported claiming its application in cancers, metabolic disorders, airway hyperresponsiveness, cardiac disorders, neurological disorders, etc. With regard to hormone-dependent cancers like breast, prostate, and other malignancies like pancreatic, colon, lung, osteosarcoma, glioma that has limited treatment options, biochanin-A revealed agreeable results in arresting cancer development. Biochanin-A has also shown therapeutic benefits when a

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… The effects of biochanin-A were similar to that of monensin, an antibiotic that is used conventionally for SARA treatment in cattles. …

Primed for global coronavirus pandemic: Emerging research and clinical outcome.

The global effort to combat and contain the coronavirus disease 2019 (COVID-19) caused by the recently discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now proceeding on a war footing. The world was slow to react to the developing crisis, but once the contours of the impending calamity became evident, the different state and non-state actors have raced to put their act together. The COVID-19 pandemic has blatantly exposed the shortcomings of our healthcare system and the limitations of medical science, despite considerable advances in recent years. To effectively tack

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… Many other approved antibiotics like ritavancin, dalbavancin, and monensin, and an anti-protozoal drug, emetine, have also been found to inhibit several coronaviruses and viruses belonging to other families, in vitro , and thus could be potentially repurposed for the treatment of COVID-19 [ 126 ]. …

Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.

Protein folding is a fundamental process ensuring that polypeptide chains acquire the correct three-dimensional structures required for biological function. This complex journey from nascent polypeptides to mature proteins is tightly regulated by the cellular proteostasis network-an integrated system of molecular chaperones, folding enzymes, and degradation machineries. Disruptions in this network lead to dysproteostasis, a pathological state implicated in a growing list of human diseases, including neurodegenerative disorders, metabolic syndromes, and cancer. In this review, we provide a comp

Natural Products as Anticancer Agents: Current Status and Future Perspectives.

Natural products have been an invaluable and useful source of anticancer agents over the years. Several compounds have been synthesized from natural products by modifying their structures or by using naturally occurring compounds as building blocks in the synthesis of these compounds for various purposes in different fields, such as biology, medicine, and engineering. Multiple modern and costly treatments have been applied to combat cancer and limit its lethality, but the results are not significantly refreshing. Natural products, which are a significant source of new therapeutic drugs, are cu

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