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RNA метилтрансферазы METTL8 устанавливает m3C32 в митохондриальном tRNASThr/Ser (UCN) для оптимизации структуры trNA и митохондриального перевода.

Модифицированные нуклеотиды в tRNA являются важными определяющими факторами сворачивания, структуры и функции. Здесь мы идентифицируем METTL8 как митохондриальный белок и активный РНК метилтрансферазы, ответственный за установку m3C32 в митохондриале человека (mt-)tRNAThr и mt-tRNAser (UCN). METTL8 имеет перекрестные связи с антикодоновой стволовой петлей (ASL) многих мт-тРНК в клетках, в связи с чем возникает вопрос о том, каким образом достигается целевая специфичность метилирования. Расчленение элементов распознавания mt-tRNA выявило наличие U34G35 и t6A37/(ms2)i6A37, которые одновременно п

Совпадение в полном тексте источника
… Evolutionary and functional analysis of yeast m 3 C methyltransferases 30 revealed a gene duplication event in fission yeast that separated the methylation activity of the S. cerevisiae Trm140 enzyme, which targets both tRNA Thr and tRNA Ser , into two distinct enzymes ( S. pombe Trm140 and Trm141). …

Acute and Chronic Cardiovascular Adverse Events in Patients with Acute Myeloid Leukemia: A Systematic Review.

Background/Objectives: Patients with acute myeloid leukemia (AML) have a higher propensity for adverse cardiovascular outcomes, primarily due to the toxic effects of chemotherapeutic agents. The purpose of this systematic review is to explore the association of acute myeloid leukemia treatment with adverse cardiovascular events. Methods: We systematically screened the literature for studies providing comparative data on cardiovascular toxicities in patients treated for acute myeloid leukemia. After the initial search, 3649 papers were screened and a final total number of 46 were included for t

Структурное и механистическое профилирование модулятуры Hurr1 vidofludimus позволяет проектировать лиганд на основе структуры.

В центре биомедицинских исследований находится фактор нейрозащиты, связанный с ядерным рецептором 1 (Nurr1, NR4A2) для его многообещающей нейрозащитной роли в болезни Паркинсона, болезни Альцгеймера и множественном склерозе. Его деятельность может контролироваться лигандами, предлагающими доступ к фармакологической модуляции Hurr1. Вместе с тем связующие эпитопы и механизмы молекулярной активации синтетических активаторов Hurr1 по-прежнему остаются труднодостижимыми, но имеют важное значение для продвижения к новым лекарствам лигандов Hurr1. Здесь мы охарактеризовали диссоциацию Hurr1 димера и

Magnitude of cancer-associated thrombosis in Africa: A systematic review and meta-analysis.

Comprehensive data on the epidemiology of cancer-related thrombosis in Africa has been sparse until recently. Thus, this review was aimed to investigate the magnitude of cancer-related thrombosis in Africa. To obtain key articles, comprehensive search was conducted using various databases. A random-effects model was used to determine the pooled magnitude. Heterogeneity across the studies was checked, and publication bias was determined. The pooled magnitude of thrombosis among cancer patients in Africa is 11.65% (95% confidence interval [CI]: 9.02-14.28). Advanced age, comorbidity, and level o

A study on a real-world data-based VTE risk prediction model for lymphoma patients.

BackgroundPatients diagnosed with malignant tumors exhibit a markedly elevated risk of venous thromboembolism (VTE), which has a negative impact on their prognosis. Currently, there is no reliable predictive model specifically for thrombosis risk in lymphoma patients. This study aims to develop and validate a machine learning model leveraging real-world data, offering a dependable risk assessment tool for the early identification of VTE in lymphoma patients.MethodsWe retrospectively analyzed 605 hospitalized patients with lymphoma between January 2019 and June 2024. Candidate predictors includ

Mitophagy related gene signature for prognosis and therapeutic evaluation in KIRC.

This study conducted a comprehensive investigation of the prognostic significance and immunological features associated with mitophagy-related gene signatures in clear cell renal cell carcinoma (KIRC). Our primary aim was to establish an optimized predictive model for precise prognosis stratification and treatment response prediction in KIRC patients. Through LASSO Cox regression analysis, we systematically identified mitophagy-related genes (MRGs) and implemented them to develop a prognostic risk stratification model. The model's reliability was rigorously validated using both internal cohort

The Role of Vitamin C in Cancer Prevention and Therapy: A Literature Review.

Vitamin C is a water-soluble antioxidant associated with the prevention of the common cold and is also a cofactor of hydrolases that participate in the synthesis of collagen and catecholamines, and in the regulation of gene expression. In cancer, vitamin C is associated with prevention, progression, and treatment, due to its general properties or its role as a pro-oxidant at high concentration. This review explores the role of vitamin C in cancer clinical trials and the aspects to consider in future studies, such as plasmatic vitamin C and metabolite excretion recording, and metabolism and tra

Эволюционно сохраненная созвездие функциональных резинов программирует реагирующую на вирус судьбу человека (эпи)генома.

Здоровье человека зависит от запутанной защитной клеточной реакции на микробные патогены, такие как вирусы. Несмотря на предпринятые значительные усилия, (эпи)геномические механизмы, используемые клетками человека для адаптации программ защитного генного экспрессия к микробным атакам, по-прежнему недостаточно изучены, главным образом из-за значительного отсутствия регистрации в vivo функциональных модулей резного регулирования (КРМ) генома человека. Здесь мы представляем реагирующую на вирус судьбу человека (эпи)генома, описываемого в наивных и инфицированных клетках функциональными геномами,

Calpastatin phosphorylation regulates radiation-induced calpain activity in glioblastoma.

Glioblastoma (GBM) is an aggressive, malignant brain tumor that inevitably develops resistance to conventional chemotherapy and radiation treatments. In order to identify signaling pathways involved in the development of radiation resistance, we performed mass spectrometry-based phospho-proteomic profiling of GBM cell lines and normal human astrocytes before and after radiation treatment. We found radiation induced phosphorylation of a number of proteins including calpastatin, specifically in GBM stem cells (GSCs). Herein, we focused on calpastatin, an endogenous inhibitor of calpain proteases

Болезни Увечье с возрастом в экспериментальной модели множественного склероза: роль иммунозенсии.

Начавшийся множественный склероз (MS) у пожилых людей соотносится с более высоким риском развития первичных прогрессивных MS, ускорения перехода к вторичным прогрессивным MS и увеличения накопления инвалидности. Это явление может быть связано с возрастными изменениями в иммунной системе: с возрастом иммунная система проходит процесс, называемый иммунной сенсацией, который характеризуется снижением функции как врожденной, так и адаптивной иммунной реакции. Такое снижение может привести к снижению способности контролировать воспаление и восстанавливать поврежденные ткани. Кроме того, пожилые люд

Ancient genes establish stress-induced mutation as a hallmark of cancer.

Cancer is sometimes depicted as a reversion to single cell behavior in cells adapted to live in a multicellular assembly. If this is the case, one would expect that mutation in cancer disrupts functional mechanisms that suppress cell-level traits detrimental to multicellularity. Such mechanisms should have evolved with or after the emergence of multicellularity. This leads to two related, but distinct hypotheses: 1) Somatic mutations in cancer will occur in genes that are younger than the emergence of multicellularity (1000 million years [MY]); and 2) genes that are frequently mutated in cance

Оценка причинно-следственного воздействия метаболомы на риск психических и нейродегенеративных расстройств.

Данные свидетельствуют о фенотипическом и биологическом переплетении между психическими и нейродегенеративными расстройствами. Дальнейшее выявление лежащих в основе взаимных и уникальных биологических механизмов может привести к появлению новых, многопорядковых и многопорядковых терапевтических целей. Метаболом представляет собой важную область для идентификации целей, поскольку метаболиты играют важнейшую роль в модуляции разнообразных биологических процессов.Мы использовали менделианскую случайность (MR) для проверки причинного воздействия ~ 1000 плазменных метаболитов и ~ 300 метаболитов на

Glucosylsphingosine (Lyso-Gb1): An Update on Its Use as a Biomarker in Gaucher Disease.

Gaucher disease (GD) is a lysosomal storage disorder caused by mutations in the glucocerebrosidase gene (GBA1), leading to acid β-glucosidase deficiency and the accumulation of glucosylceramide-derived glycosphingolipids. Its three phenotypes (non-neuronopathic, acute neuronopathic, and chronic neuronopathic) have variable clinical presentations including hepatosplenomegaly, cytopenia, bone disease, and neurological involvement. Early diagnosis and treatment are critical for improving outcomes, but GD is under-recognized due to non-specific symptoms and limited access to appropriate diagnostic

Canine Cancer: Strategies in Experimental Therapeutics.

Cancer is the most common cause of death in adult dogs. Many features of spontaneously developing tumors in pet dogs contribute to their potential utility as a human disease model. These include similar environmental exposures, similar clonal evolution as it applies to important factors such as immune avoidance, a favorable body size for imaging and serial biopsy, and a relatively contracted time course of disease progression, which makes evaluation of temporal endpoints such as progression free or overall survival feasible in a comparatively short time frame. These criteria have been leverage

CAR-T Therapies in Solid Tumors: Opportunities and Challenges.

Purpose of reviewThis review will discuss the challenges facing chimeric antigen receptor (CAR)-T cell application for solid tumors and opportunities to overcome these obstacles. In addition, this review will examine therapies that are in development for pediatric solid tumors.Recent findingsThe similar success of CAR-T cell treatment for hematological malignancies has not been observed in solid tumors because of the hostile tumor microenvironment and tumor heterogeneity. Most strategies developed to combat these limitations emphasize combinatorial techniques that still require further testing

Unveiling the role of histone deacetylases in neurological diseases: focus on epilepsy.

Epilepsy remains a prevalent chronic neurological disease that is featured by aberrant, recurrent and hypersynchronous discharge of neurons and poses a great challenge to healthcare systems. Although several therapeutic interventions are successfully utilized for treating epilepsy, they can merely provide symptom relief but cannot exert disease-modifying effect. Therefore, it is of urgent need to explore other potential mechanism to develop a novel approach to delay the epileptic progression. Since approximately 30 years ago, histone deacetylases (HDACs), the versatile epigenetic regulators re

Determining Risk Factors Associated with Cardiovascular Complications in Patients with Acute Leukemia: A Systematic Review.

BackgroundPatients with acute leukemia (AL) are at heightened risk of cardiovascular complications due to both disease-related and treatment-related factors. These complications include heart failure, arrhythmias, myocardial infarction, and thromboembolic events which may significantly impact morbidity and mortality.ObjectiveTo identify the risk factors contributing to cardiovascular complications in patients with acute leukemia.MethodsThis systematic review was conducted according to the PRISMA reporting guideline. Multiple databases including PubMed, Scopus, IEEE Xplore, the Cochrane Library

Medication-Related Osteonecrosis of the Jaw: A Systematic Review and a Bioinformatic Analysis.

The objective was to evaluate the current evidence regarding the etiology of medication-related osteonecrosis of the jaw (MRONJ). This study systematically reviewed the literature by searching PubMed, Web of Science, and ProQuest databases for genes, proteins, and microRNAs associated with MRONJ from the earliest records through April 2023. Conference abstracts, letters, review articles, non-human studies, and non-English publications were excluded. Twelve studies meeting the inclusion criteria involving exposure of human oral mucosa, blood, serum, saliva, or adjacent bone or periodontium to a

< < Элотузумаб > > CD16-Independent NK Спутниковая цитотоксичность против ячеек миеломы путем регулирования нескольких NK-подкрепляющих генов

Множественная миелома (ММ) — неразрешимая гематологическая порча, вызванная аномалиями в плазменных клетках. Комбинированная терапия с использованием антител и эффектов естественного убийцы (НК), которые являются врожденными иммунными клетками с безопасной и мощной антитумбурной активностью, является перспективным подходом к онкологической иммунной терапии и может усилить антитумберные эффекты. Elotuzumab (Elo) — антитело с иммунной оптимистикой, предназначенное для семейства молекул лимфоцитной активации. 7 (SLAMF7) на поверхности клеток MM и NK. Мы подтвердили, что Эло активно пропагандирует

A Systematic Review of Machine Learning Techniques in Hematopoietic Stem Cell Transplantation (HSCT).

Machine learning techniques are widely used nowadays in the healthcare domain for the diagnosis, prognosis, and treatment of diseases. These techniques have applications in the field of hematopoietic cell transplantation (HCT), which is a potentially curative therapy for hematological malignancies. Herein, a systematic review of the application of machine learning (ML) techniques in the HCT setting was conducted. We examined the type of data streams included, specific ML techniques used, and type of clinical outcomes measured. A systematic review of English articles using PubMed, Scopus, Web o