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Okay, so I need to translate this medical text into Russian. Let me first read through the original sentence carefully. The sentence is: "N-Azacytidine Inhibits Myeloma Cell Growth While Preserving Multiple Myeloma Patient Derived-Bone Marrow Mesenchymal Stromal Cells Differentiation." Hmm, the key here is to translate it accurately using proper clinical and anatomical terms. Let me break it down. First, "N-Azacytidine" is a drug name. In Russian, drug names are often transliterated or use the original name with some adaptation. I think in Russian medical literature, they might use the international nonproprietary name, which is "N-азацидидин" or maybe "N-азацидид"? Wait, no, let me check. Wait, the international nonproprietary name for N-Azacytidine is "азацидидин" (azacitidine) in Russian. Wait, but the chemical name is N-Azacytidine, which is a nucleoside analog. In Russian, the term for azacitidine is "азацидидин" (azacitidine). Wait, but the original says "N-Azacytidine", so maybe it's "N-азацидидин" but I think in Russian medical terms, they might just use "азацидидин" without the

Множественная миелома (ММ) — неизлечимая гематологическая порча, вызванная аномальным распространением неизлечимо дифференцированных плазменных клеток в костном мозге. Текущие исследования показывают, что N-azacytidine как эпигенетическое лекарство и нуклеозный метаболический ингибитор могут быть эффективными при лечении MM. Вместе с тем данные о мезенхимальных стромальных клетках костного мозга (МСЦВ) в качестве критической клеточной популяции в процессах гематопоизи и реконструирования костей ограничены.МЕТОДЫ: Воздействие N-azacytidine на клеточную линию миэломы AMO-1, мезенхимальные строма…

Отталкиваю меняющееся управление хмурящейся множественной миеломой.

Множественная миелома (SMM) представляет собой промежуточную клиническую стадию между моноклонной гаммопатией неопределенного значения (MMUS) и симптоматической множественной миеломой (MM). ШМ сопряжена с весьма изменчивым риском перехода к ММ, что требует индивидуальной стратификации рисков для руководства управлением. Исторически модели риска основывались на статических клинических маркерах, отражающих бремя опухоли, для прогнозирования прогресса. Несмотря на свою полезность, эти модели не смогли зафиксировать лежащую в основе этого заболевания биологическую неоднородность. Последние достиже

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… These included aging‐related signatures, germinal center‐associated polymerase eta somatic hypermutation, reactive oxygen species‐related damage, and apolipoprotein B mRNA editing catalytic polypeptide‐like (APOBEC) enzymes. 58 , 59 Notably, mutational activity of APOBEC cytidine deaminases has been …

Recent Clinical Update of Acute Myeloid Leukemia: Focus on Epigenetic Therapies.

Acute myeloid leukemia (AML) is a complicated disease characterized by genetic heterogeneity and simultaneous alterations in multiple genes. For decades, its only curative method has been intensive induction chemotherapy with or without allogeneic hematopoietic stem cell transplantation, and this approach cannot be applied to elderly patients, who make up more than 50% of AML patients. Recent advances in genomics facilitated the elucidation of various mutations related to AML, and the most frequent mutations were discovered in epigenetic regulators. Alterations to epigenetic modifications that

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… Currently, 2 azanucleosides that are pyrimidine analogues of cytidine, azacitidine, and decitabine are used as treatments for AML and myelodysplastic syndrome (MDS) patients who are not eligible for intensive chemotherapy. 11 , 13 These agents incorporate into DNA (decitabine) or RNA (azacitidine) and …

Therapies and nanotherapies for cervical cancer (Review).

Cervical cancer (CC) is a major global health concern, ranking fourth worldwide in mortality, due to its high death rate and strong link to persistent high-risk human papillomavirus infections, which drive cancer progression through cellular dysregulation. Conventional therapies used in the treatment of CC have significant disadvantages, such as adverse side effects that affect the quality of life of patients. These side effects may include nausea, vomiting, fatigue, hair loss, fertility problems, damage to nearby organs and systemic toxicity. To address these challenges, there has been an inc

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… lomustine | | Inhibition of DNA replication and transcription | Platinum analogs: Carboplatin, cisplatin and oxaliplatin | | | Triazenes: Dacarbazine, procarbazine and temozolamide | | | Alkyl sulfonate: Busulfan | | | Ethyleneimine: Thiotepa | Antimetabolites | Inhibition of DNA replication | Cytidine …

Hydralazine and Panobinostat Attenuate Malignant Properties of Prostate Cancer Cell Lines.

Among the well-established alterations contributing to prostate cancer (PCa) pathogenesis, epigenetics is an important player in its development and aggressive disease state. Moreover, since no curative therapies are available for advanced stage disease, there is an urgent need for novel therapeutic strategies targeting this subset of patients. Thus, we aimed to evaluate the combined antineoplastic effects of DNA methylation inhibitor hydralazine and histone deacetylase inhibitors panobinostat and valproic acid in several prostate cell lines. The effect of these drugs was assessed in four PCa

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… Recently, a combination of a DNMTi, 5-aza-2′-deoxycytidine (5-Aza-CdR) and a cytidine deaminase inhibitor, cedazuridine, has been approved for the treatment of myelodysplastic syndromes and chronic myelomonocytic leukemia [ 30 ]. …

Review of COVID-19 Therapeutics by Mechanism: From Discovery to Approval.

The global research and pharmaceutical community rapidly mobilized to develop treatments for coronavirus disease 2019 (COVID-19). Existing treatments have been repurposed and new drugs have emerged. Here we summarize mechanisms and clinical trials of COVID-19 therapeutics approved or in development. Two reviewers, working independently, reviewed published data for approved COVID-19 vaccines and drugs, as well as developmental pipelines, using databases from the following organizations: United States Food and Drug Administration (US-FDA), European Medicines Agency (EMA), Japanese Pharmaceutical

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… . | Cytidine nucleoside analogue to inhibition of viral replication. | EUA | 13 14 15 Azvudine | 2′-deoxy-2′-β-fluoro-4′-azidocytidine | Genuine Biotech | China | Azvudine 5 mg per day orally. | Nucleoside analogue | NMPA | 16 17 Veklury | Remdesivir | Gilead Sciences | USA | Remdesivir 200 mg via intravenous … It is metabolized to a cytidine nucleoside analog, forming a pharmacologically active ribonucleoside triphosphate (NHC-TP). NHC-TP incorporation into SARS-CoV-2 RNA by viral RNA polymerase (nsp12) introduces copying errors during viral RNA replication. …

Three- размерная структура комплекса Palbociclib-HIV TAR.

Мы представляем структуру HIV-1 элемент реакции на трансактивацию (TAR), связанный с киназным ингибитором palbociclib, однозначным лигандом nM и ингибитором с низким значением nM комплекса супер удлинения. Маленькая молекула перестраивает РНК, чтобы создать глубокий связующий карман в новой структуре ТАР. Он заменяет A22 на "интермолекулярную пару" с U40, создавая постоянно сложенную пару. 11 спираль, которая включает в себя three :: новые три базы, включая саму A22 и нуклеотиды UCU. Мутация нуклеотидов в связующем кармане или небольшие модификации малой молекулы, отменяющей связующую способно

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… The broad signal at 15.6 ( Supplementary Figs S17 and 21 ) is at the chemical shifts of cytidine protons in C+GC base triples [ 49 , 50 ], but the 180 ppm 15 N shift is unexpected. Nevertheless, all resonances for the C24 base appear as one major and one minor peak ( Supplementary Fig. …

Фармакомикробиомика: От взаимодействия хост-микробиома-наркотики к клиническому переводу в докторскую медицину.

Заметная межиндивидуальная изменчивость реакции на наркотики по-прежнему является серьезной проблемой в области клинической фармакологии и не может быть в полной мере объяснена только генетикой принимающей страны. Растущие данные свидетельствуют о том, что кишечная микробиота является дополнительным фактором, определяющим эффективность и токсичность наркотиков посредством двустороннего взаимодействия с фармакологической терапией. Это признание привело к появлению фармакомикробиомики - области, которая изучает, как микробные сообщества влияют на утилизацию наркотиков и реагирование на них, и ка

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… In vitro + Animal (mouse) | [ 36 ] Oestrogens (oral contraceptives) | Glucuronide deconjugation | β-glucuronidases (estrobolome) | Increased enterohepatic recirculation; potential reduced contraceptive efficacy with antibiotics | In vitro | [ 37 , 38 , 39 ] Gemcitabine | Deamination/inactivation | Cytidine …

Anti-PEG Antibodies and Their Biological Impact on PEGylated Drugs: Challenges and Strategies for Optimization.

Polyethylene glycol (PEG) has been widely utilized in optimizing therapeutics due to its excellent biocompatibility and chemical stability. However, multiple dosing of PEGylated drugs may result in toxicity due to PEG accumulation in tissues, leading to the formation of anti-PEG antibodies (APAs), which can accelerate drug clearance, reduce efficacy, and alongside enhanced side effects, such as allergic reactions. Notably, pre-existing APAs have also been detected in individuals with no prior exposure to PEGylated drugs, raising additional clinical concerns. This review summarizes the mechanis

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… The interaction of CD40 ligand on TFH cells with B cells triggers the expression of activation-induced cytidine deaminase (AID) [ 23 ]. …

2021 European Myeloma Network review and consensus statement on smoldering multiple myeloma: how to distinguish (and manage) Dr. Jekyll and Mr. Hyde.

According to the updated International Myeloma Working Group criteria, smoldering multiple myeloma (SMM) is an asymptomatic plasma cell disorder characterized by an M-component >3 g/dL, bone marrow plasma cell infiltration >10% and <60%, and absence of any myeloma-defining event. Active multiple myeloma is preceded by SMM, with a median time to progression of approximately 5 years. Cases of SMM range from the extremes of "monoclonal gammopathy of undetermined significance-like", in which patients never progress during their lifetimes, to "early multiple myeloma", in which transformation into s

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… Late mutations, developing at the time of progression, arise from aberrant activity of the APOBEC family of cytidine deaminases, whose activity is absent in normal plasma cells. 33-34 In clinical practice, recurrent translocations or hyperdiploidy can be assessed by fluorescence in situ hybridization …

Oncogenic Roles and Inhibitors of DNMT1, DNMT3A, and DNMT3B in Acute Myeloid Leukaemia.

Epigenetic alteration has been proposed to give rise to numerous classic hallmarks of cancer. Impaired DNA methylation plays a central role in the onset and progression of several types of malignancies, and DNA methylation is mediated by DNA methyltransferases (DNMTs) consisting of DNMT1, DNMT3A, and DNMT3B. DNMTs are frequently implicated in the pathogenesis and aggressiveness of acute myeloid leukaemia (AML) patients. In this review, we describe and discuss the oncogenic roles of DNMT1, DNMT3A, and DNMT3B in AML. The clinical response predictive roles of DNMTs in clinical trials utilising hy

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… This is thought to be due to degradation of both agents by cytidine-deaminase (CDA) present in the liver, spleen, and intestinal epithelium, resulting in their short plasma half-life. 93 – 95 Guadecitabine (SGI-110), a dinucleotide of decitabine, demonstrates improved stability in plasma due to CDA resistance …

The impact of age-related syndromes on ICU process and outcomes in very old patients.

In this narrative review, we describe the most important age-related "syndromes" found in the old ICU patients. The syndromes are frailty, comorbidity, cognitive decline, malnutrition, sarcopenia, loss of functional autonomy, immunosenescence and inflam-ageing. The underlying geriatric condition, together with the admission diagnosis and the acute severity contribute to the short-term, but also to the long-term prognosis. Besides mortality, functional status and quality of life are major outcome variables. The geriatric assessment is a key tool for long-term qualitative outcome, while immediat

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… Frasca D Landin AM Lechner SC Ryan JG Schwartz R Riley RL Aging down-regulates the transcription factor E2A, activation-induced cytidine deaminase, and Ig class switch in human B cells J Immunol 2008 180 5283 5290 10.4049/jimmunol.180.8.5283 18390709 19. …

Immunotherapy Combined with Metronomic Dosing: An Effective Approach for the Treatment of NSCLC.

Pioneering studies on tumor and immune cell interactions have highlighted immune checkpoint inhibitors (ICIs) as revolutionizing interventions for the management of NSCLC, typically combined with traditional MTD chemotherapies, which usually lead to toxicities and resistance to treatment. Alternatively, MTR chemotherapy is based on the daily low dose administration of chemotherapeutics, preventing tumor growth indirectly by targeting the tumor microenvironment. The effects of MTR administration of an oral prodrug of gemcitabine (OralGem), alone or with anti-PD1, were evaluated. Relevant in vit

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… Following gemcitabine dosing, rapid deamination by cytidine deaminase leads to the production of the inactive metabolite, dFdU [ 3 ]. …

Emerging disease-modifying therapies for sickle cell disease.

Sickle cell disease afflicts millions of people worldwide and approximately 100,000 Americans. Complications are myriad and arise as a result of complex pathological pathways 'downstream' to a point mutation in DNA, and include red blood cell membrane damage, inflammation, chronic hemolytic anemia with episodic vaso-occlusion, ischemia and pain, and ultimately risk of cumulative organ damage with reduced lifespan of affected individuals. The National Heart, Lung, and Blood Institute's 2014 evidence-based guideline for sickle cell disease management states that additional research is needed bef

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… Decitabine with ( NCT01685515 ) or without ( NCT01375608 ) tetrahydrouridine (a cytidine deaminase inhibitor that prevents rapid deactivation of decitabine, thereby allowing the use of an oral formulation of this latter) is a chemotherapy used to treat myelodysplastic syndrome and acute myeloid leukemia …

Ассоциированные клетки B в аутоиммунных болезнях: патогенез и клинические последствия.

Будучи разнородным подмножеством клеток В, связанные с возрастом клетки В (ABC) имеют различные транскрипционные профили, процессы экстрафолликулярной дифференциации и множественные функции в автоматическом иммунитете. Сигналы TLR7 и TLR9 наряду с стимуляцией IFN-__ и IL-21 имеют важное значение для дифференциации ABC, которая также регулируется хемокиновыми рецепторами, включая CXCR3 и CCR2, и интегралами, включая CD11b и CD11c. С учетом их функций, связанных с поглощением и представлением антигенов, секрецией цитокина, а также активацией ячеек Т, ABC демонстрируют потенциал в прогнозе, диагн

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… Activated MyD88 and NF-κB signaling initiates the transcription of proinflammatory cytokines and may cause activation-induced cytidine deaminase, contributing to SHM and class-switch recombination in ABCs [ 28 ]. TLR9 synergized with BCR to stimulate antigen-specific B cells [ 29 ]. …

Transplant oncology and anti-cancer immunosuppressants.

Organ transplantation is a life-saving intervention that enhances the quality of life for patients with end-stage organ failure. However, long-term immunosuppressive therapy is required to prevent allogeneic graft rejection, which inadvertently elevates the risk of post-transplant malignancies, especially for liver transplant recipients with a prior history of liver cancer. In response, the emerging field of transplant oncology integrates principles from oncology and immunology to improve outcomes for patients at high risk of tumor occurrence or recurrence following transplantation. Therefore,

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… Following oral administration, CAP is absorbed in the gastrointestinal tract and subsequently metabolized into its intermediary forms: 5’-deoxy-5-fluorocytidine and 5’-deoxy-5-fluorouridine, through the action of carboxylesterase and cytidine deaminase, respectively. …

Clinical Aspects of B Cell Immunodeficiencies: The Past, the Present and the Future.

B cells and antibodies are indispensable for host immunity. Our understanding of the mechanistic processes that underpin how B cells operate has left an indelible mark on the field of clinical pathology, and recently has also dramatically reshaped the therapeutic landscape of diseases that were once considered incurable. Evaluating patients with primary immunodeficiency diseases (PID)/inborn errors of immunity (IEI) that primarily affect B cells, offers us an opportunity to further our understanding of how B cells develop, mature, function and, in certain instances, cause further disease. In t

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… Although additional genes have been identified in non-X-linked HIGM syndromes, in this report we will briefly touch upon CD40, activation-induced cytidine deaminase (AID) and uracil-DNA glycosylase (UNG) deficiency disorders. 3.3.1. …

Chemotherapy Side-Effects: Not All DNA Damage Is Equal.

Recent advances have increased survival rates of children and adults suffering from cancer thanks to effective anti-cancer therapy, such as chemotherapy. However, during treatment and later in life they are frequently confronted with the severe negative side-effects of their life-saving treatment. The occurrence of numerous features of accelerated aging, seriously affecting quality of life, has now become one of the most pressing problems associated with (pediatric) cancer treatment. Chemotherapies frequently target and damage the DNA, causing mutations or genome instability, a major hallmark

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… It is a pyrimidine nucleoside analogue mimicking cytidine and deoxycytidine, which are necessary for DNA synthesis [ 43 ]. …

Спасение гиппокампальной синаптической пластичности и эффективности памяти Финголимода (FTY720) в модели APP/PS1 болезни Альцгеймера сопровождается коррекцией метаболизма финголипидов, полиаминов и фосфолипидного насыщенного состава.

Ранее, наши метаболомические, транскриптомные и геномные исследования характеризовали путь церамида/шфингомилена как терапевтическую цель в болезни Альцгеймера, и мы показали, что FTY720, фингозин-1-фосфахатный рецептор, утвержденный для лечения множественных склерозов, восстанавливает синаптическая пластичность и память в мышах APP/PS1. Для дальнейшего изучения того, как FTY720 спасает патологию, мы провели метаболический анализ мозга, плазмы и печени обученных APP/PS1 и диких мышей. APP/PS1 мыши продемонстрировали локальные нарушения мозга в полиаминах, фосфолипидах и сфинголипидах. Большинс

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… PEs are synthesized in mitochondria from PSs through the action of phosphatidylserine decarboxylase (PSD) although there is another major pathway for PE synthesis from cytidine diphosphate (CDP)-ethanolamine and diglycerides (DGs). …

Potential Immunotherapy Targets for Liver-Directed Therapies, and the Current Scope of Immunotherapeutics for Liver-Related Malignancies.

Liver cancer, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, is increasing in incidence and mortality across the globe. An improved understanding of the complex tumor microenvironment has opened many therapeutic doors and led to the development of novel pharmaceuticals targeting cellular signaling pathways or immune checkpoints. These interventions have significantly improved tumor control rates and patient outcomes, both in clinical trials and in real-world practice. Interventional radiologists play an important role in the multidisciplinary team given their expertise

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… Decitabine acts as a cytidine analogue, integrating itself into DNA and blocking methylation at that site. Following two phase I/II trials, its safety and efficacy at low doses have been validated both alone and in combination with chemotherapy or immunotherapy [ 207 , 208 ]. … Modifying decitabine with deoxyguanosine in an attempt to increase stability and prevent degradation by cytidine deaminase resulted in the production of guadecitabine. …