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Демиелинция производит сдвиг в населении кортикальных нейронов, которые синапсируют с каллосальными олигодендроцитными клетками.

Клетки потомства олигодендроцитов (ОРК) получают синаптическое воздействие от различных нейронов в мозгу развивающихся и взрослых. Понимание того, меняются ли нейронные популяции, которые синапируют с OPC в здоровом мозге в результате обезвоживания и/или ремиэлирования, может способствовать совершенствованию стратегий нейрозащиты или миелинового ремонта, разрабатываемых для демиелинизирующих заболеваний, таких, как множественный склероз. Чтобы изучить эту возможность, мы использовали трансгенную технологию крелокса, чтобы облегчить инфекцию ОПС модифицированным вирусом бешенства, что позволяет

Immunomodulatory effects of the Agaricus blazei Murrill-based mushroom extract AndoSan in patients with multiple myeloma undergoing high dose chemotherapy and autologous stem cell transplantation: a randomized, double blinded clinical study.

Forty patients with multiple myeloma scheduled to undergo high dose chemotherapy with autologous stem cell support were randomized in a double blinded fashion to receive adjuvant treatment with the mushroom extract AndoSan, containing 82% of Agaricus blazei Murrill (19 patients) or placebo (21 patients). Intake of the study product started on the day of stem cell mobilizing chemotherapy and continued until the end of aplasia after high dose chemotherapy, a period of about seven weeks. Thirty-three patients were evaluable for all study endpoints, while all 40 included patients were evaluable fo

Evaluating the safety and feasibility of allogeneic NK cell infusion in high-risk lymphoma patients post-autologous stem cell transplantation.

Lymphoma, a cancer with poor prognosis is a growing global health challenge that encompasses two primary types, Hodgkin (HL) and non-Hodgkin lymphoma (NHL), each further divided into various subtypes with distinct biological behaviors. Conventional therapeutic strategies include chemotherapy, radiation, surgery, and autologous hematopoietic stem cell transplantation (auto-HSCT). Natural killer (NK) cells exhibit intrinsic cytotoxicity against tumor cells without the need for prior immunization or activation. In this prospective clinical trial, we evaluated the feasibility of allogeneic NK cell

SMAD2 S-palmitoylation promotes its linker region phosphorylation and TH17 cell differentiation in a mouse model of multiple sclerosis.

The transcriptional regulators SMAD2 and SMAD3 share the same primary signaling pathway in response to the cytokine TGFβ. However, whereas SMAD2 stimulates the differentiation of naive CD4+ T cells into proinflammatory T helper 17 cells (TH17 cells), SMAD3 stimulates the differentiation of anti-inflammatory regulatory T cells (Treg cells). Here, we report a dynamic SMAD2-specific posttranslational modification important for TH17 cell differentiation. SMAD2, but not SMAD3, was reversibly S-palmitoylated at cysteine-41 and cysteine-81 by the palmitoyltransferase DHHC7 and depalmitoylated by the

Крисдесалазин смягчает воспаление в экспериментальной аутоиммунной энцефаломиэлитовой модели склерозной мыши, регулируя иммунную систему.

Микроглиа/макропатии участвуют в разработке и восстановлении экспериментального аутоиммунного энцефаломиелита (EAE), а процесс перехода на макрофаж M1 (провоспалительное)/M2 (против воспаления) осуществляется на этапе развития заболеваний EAE. Мы провели оценку эффективности хрисдезалезина (нового микросомального простагландина E2 ингибитора синтазы-1) в модели EAE, включая его иммунную силу регулирования в липополисакхаридно-стимулированных макрофагах, и его нейрозащитное воздействие в макрофаге-еврокультуре. Крисдезалезин значительно смягчил клинические симптомы, интрузивную инфильтрацию кле

Bortezomib-Loaded Mesoporous Silica Nanoparticles Selectively Alter Metabolism and Induce Death in Multiple Myeloma Cells.

A mesoporous silica-based nanodevice bearing the antineoplastic drug bortezomib (BTZ), whose release is triggered in acidic environment and grafted with folic acid (FOL) as a targeting function (FOL-MSN-BTZ) was tested on folate receptor overexpressing (FR+) multiple myeloma (MM) cells and on FR negative (FR-) normal cells. FOL-MSN-BTZ efficacy studies were conducted by means of growth experiments, TEM, TUNEL assay and Western Blotting analysis (WB). Metabolic investigations were performed to assess cells metabolic response to MSNs treatments. FOL-MSN-BTZ exclusively killed FR+ MM cells, leadi

Regulation of Mucin 1 and multidrug resistance protein 1 by honokiol enhances the efficacy of doxorubicin-mediated growth suppression in mammary carcinoma cells.

Understanding the link between chemoresistance and cancer progression may identify future targeted therapy for breast cancer. One of the mechanisms by which chemoresistance is attained in cancer cells is mediated through the expression of multidrug resistance proteins (MRPs). Acquiring drug resistance has been correlated to the emergence of metastasis, accounting for the progression of the disease. One of the diagnostic markers of metastatic progression is the overexpression of a transmembrane protein called Mucin 1 (MUC1) which has been implicated in reduced survival rate. The objective of th

Neurodegeneration: can metabolites from Eremurus persicus help?

The number of patients affected by neurodegenerative diseases is increasing worldwide, and no effective treatments have been developed yet. Although precision medicine could represent a powerful tool, it remains a challenge due to the high variability among patients. To identify molecules acting with innovative mechanisms of action, we performed a computational investigation using SAFAN technology, focusing specifically on HuD. This target belongs to the human embryonic lethal abnormal visual-like (ELAV) proteins and plays a key role in neuronal plasticity and differentiation. The results high

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… Sigma-1 receptor agonists acting on aquaporin-mediated H2O2 permeability: new tools for counteracting oxidative stress. Int. J. Mol. Sci. 22, 9790. 10.3390/ijms22189790 Polavarapu P. L. (2016). Chiroptical spectroscopy. …

Conditional deletion of E11/podoplanin in bone protects against load-induced osteoarthritis.

BACKGROUND: Subchondral bone (SCB) thickening is one of the earliest detectable changes in osteoarthritic joints and is considered a potential trigger for subsequent articular cartilage degeneration. In this manuscript, we examine whether disruption to the SCB osteocyte network contributes to the initiation and pathogenesis of osteoarthritis. METHODS: We examined expression patterns of the glycoprotein E11/podoplanin by immunohistochemical labelling in murine, human and canine osteoarthritis models. We also examined the effects of twice-weekly administration of Bortezomib, a proteasome inhibi

:: разработка системы запретов на использование кинжалов на основе капсаицина для модуляции взаимодействия киназы A/PHB2 и митофагии в раковых клетках.

A/AURKA — киназа серена/трионина, часто перевоплощающаяся в рак. Недавние открытия указывают на подклеточные пулы АУРКА, в том числе в митохондрии. Там AURKA вызывает расчистку органеллой митофагией вместе с автоматическим посредником LC3 и его рецептором PHB2. Здесь мы показываем, что натуральный продукт капсаицин изменяет взаимодействие AURKA/PHB2. Мы синтезируем 16 Аналоговые аналоги капсаицина и передача энергии/флюоресценция Förster's Energy Transport/Fluorescence Life Time Imageing Microscope (FRET/FLIM) в клетках рака груди показывают, что соединения 12 и 13 :: расширение взаимодействия

Доказательства потенциала гуанидов против Leishmania (Viannia) braziliensis: исследование витро эффективности, токсичности и влияния на ответ иммунной системы.

Лейшманиаз — это сложная группа инфекционных и паразитарных заболеваний, которая поражает десятки тысяч людей на пяти континентах. Лечение лейшманиаза остается сложной задачей, так как оно зависит от лекарств, известных своей высокой токсичностью и ограниченной эффективностью, что делает необходимым поиск новых молекул, которые обеспечивали бы большую эффективность и безопасность. Настоящее исследование посвящено изучению влияния семи синтетических гуанидиновых производных (LQOF-G1, LQOF-G2, LQOF-G6, LQOF-G7, LQOF-G32, LQOF-G35 и LQOF-G36) на паразита Leishmania (Viannia) braziliensis и витроп

Arachidonic acid suppresses lung cancer cell growth and modulates lipid metabolism and the ERK/PPARγ signaling pathway.

Lung cancer remains the leading cause of cancer-related mortality worldwide, necessitating the development of new treatment strategies. Arachidonic acid (ARA), a polyunsaturated fatty acid, shows promise in cancer therapy due to its potential anti-tumor effects, although its role in lung cancer remains unclear. This study investigated the effects and underlying mechanism of ARA on A549 and NCI-H1299 lung cancer cells. In vitro assays were used to assess cell viability, apoptosis, colony formation, lipid droplet formation, and changes in cellular lipid content. ARA dose-dependently suppressed c

From Nature to Synthetic Compounds: Novel 1(N),2,3 Trisubstituted-5-oxopyrrolidines Targeting Multiple Myeloma Cells.

The insurgence of drug resistance in treating Multiple Myeloma (MM) still represents a major hamper in finding effective treatments, although over the past decades new classes of drugs, such as proteasome inhibitors and immunomodulatory drugs, have been discovered. Recently, our research team, within a Nature-Aided Drug Discovery project, isolated from Hibiscus Sabdariffa L. calyces the secondary metabolite called Hib-ester which possesses antiproliferative properties against human multiple myeloma RPMI 8226 cells, reduces migration and cell invasion and inhibits proteasome without neurotoxic

MAIT Cells in the Bone Marrow of Patients with Aplastic Anemia.

Mucosal-associated invariant T cells (MAIT cells) are a subset of T cells with innate, effector-like properties that play an essential role in the immune response to microbial infections. In humans, MAIT cells are detectable in the blood, liver, and lungs, but little is known about the frequency of these cells in the bone marrow. Also, the pathogenic role, if any, of MAIT cells in the development of aplastic anemia, a disease with an exquisite origin in the bone marrow, is currently unknown. We investigated the frequency and clinical relevance of bone marrow MAIT cells in a cohort of 14 patien

Biomedical Promise of Sustainable Microwave-Engineered Symmetric Curcumin Derivatives.

Curcumin is a polyphenol of the Curcuma longa plant, which can be used for various medicinal purposes, such as inflammation and cancer treatment. In this context, two symmetric curcumin derivatives (D1-(1E,6E)-1,7-bis(4-acetamidophenyl)hepta-1,6-diene-3,5-dione and D2-p,p-dihydroxy di-cinnamoyl methane) were obtained by the microwave-based method and evaluated for their antitumoral effect on human cervix cancer in comparison with toxicity on non-tumoral cells, taking into account that they were predicted to act as apoptosis agonists or anti-inflammatory agents. The HeLa cell line was incubated

Новое понимание механизма нейрохимического несбалансированности при множественном склерозе: ненормальный перенос внеклеточного пространства мозга.

Нейрохимический дисбаланс является фактором, способствующим возникновению неврологических симптомов при множественном склерозе (МС). Взрослая милиновая оболочка имеет решающее значение для транспортировки веществ в внеклеточном пространстве (ЭКС) и для поддержания местного гомеостаза. Поэтому мы предположим, что нарушение переноса ЭКС после демиелионирующих повреждений может привести к нейрохимическому дисбалансу в MS. В рамках нынешнего исследования для изучения пространственных нейрохимических изменений использовалась односторонняя модель MS, вызванная лизофосфатидилхолином. Результаты показ

Notch signaling drives multiple myeloma induced osteoclastogenesis.

Multiple myeloma (MM) is closely associated with bone destruction. Once migrated to the bone marrow, MM cells unbalance bone formation and resorption via the recruitment and maturation of osteoclast precursors. The Notch pathway plays a key role in different types of cancer and drives several biological processes relevant in MM, including cell localization within the bone marrow, proliferation, survival and pharmacological resistance. Here we present evidences that MM can efficiently drive osteoclastogenesis by contemporaneously activating Notch signaling on tumor cells and osteoclasts through

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

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

RXR Agonists Enhance Lenalidomide Anti-Myeloma Activity and T Cell Functions while Retaining Glucose-Lowering Effect.

Retinoid X receptor (RXR) heterodimerizes with the PPAR nuclear hormone receptor and regulates its downstream events. We investigated the effects of RXR agonists (LG100754, bexarotene, AGN194204, and LG101506) on lenalidomide's anti-myeloma activity, T cell functions, and the level of glucose and lipids in vivo. Genetic overexpression and CRISPR/Cas9 knockout experiments were conducted in multiple myeloma (MM) cell lines and Jurkat T cell lines to determine the roles of CRBN in RXR-agonist mediated effects. A xenograft mouse model of MM was established to determine the combination effect of LG