Результаты поиска

Стратегия выбора субстрата, взаимно исключающаяся, у человека m3C RNA трансферазы METTL2A и METTL6.

tRNAs содержат наиболее разнообразные посттранскрипционные модификации. 3-метилцитидин (m3C) широко распределяется на позиции C32 (m3C32) у эукариотических tRNAThr и tRNASer. m3C32 модифицируется единственным метилтрансферазой Trm140 у дрожжей-попыток; однако для его биогенеза участвуют два (Trm140 и Trm141 у деления дрожжей) или три энзима (METTL2A, METTL2B и METTL6 у млекопитающих). До сих пор неизвестно обоснование существования нескольких метилтрансфераз m3C32 и их механизм дифференциации по субстрату. Здесь мы обнаружили, что оба METTL2A и METTL2B выражены в живых организмах. Мы выделили

Регулирование ДИ микроцина и протеолитическое декольте являются уникальными среди известных микроцинов.

Microcin PDI подавляет разнообразие патогенных эшеричий с помощью белка-эффектора, МакпМ. В этом исследовании мы продемонстрировали, что выражение ингибиторского фенотипа вызывается при низких осмолярных условиях, а его выражение контролируется главным образом EnvZ/OmpR. two- компонентная система регулирования. Функциональные, мутагенезовые и дополняющие эксперименты были использованы для эмпирической демонстрации того, что ЭнвЗ требуется для ингибиторского фенотипа и что регулирование mcpM зависит от привязки фосфорилата OmpR к области mcpM. Фосфорилаты могут распознавать three :: различные и

Нейтрофильная активация и повторное расширение CAR-T, лежащее в основе синдрома высвобождения цитокина, во время цилакабтагенской автолексельной терапии в множестве миеломы.

Синдром цитокина (CRS) является наиболее распространенным осложнением химерика антигенного рецептора, перенаправления Т клеток (CAR-T). Существенно улучшено регулирование токсичности CAR-T, однако ДУС по-прежнему является одной из главных проблем в области безопасности. Здесь мы следим уровням сыворотки цитокина и циркулируем транскриптомы иммунных клеток в продольном направлении. 26 для понимания иммунологической кинетики CRS. Мы видим, что, хотя T лимфоциты и моноциты/макропаты являются основным общим источником цитокина в виде ДУС, нейтрофильная активация достигла пиков ранее, до появления

Recent advances in management of COVID-19: A review.

The coronavirus disease 2019 (COVID-19) pandemic caused and is still causing significant mortality and economic consequences all over the globe. As of today, there are three U.S Food and Drug administration (FDA) approved vaccines, Pfizer-BioNTech, Moderna and Janssen COVID-19 vaccine. Also, the antiviral drug remdesivir and two combinations of monoclonal antibodies are authorized for Emergency use (EUA) in certain patients. Furthermore, baricitinib was approved in Japan (April 23, 2021). Despite available vaccines and EUA, pharmacological therapy for the prevention and treatment of COVID-19 i

mRNA vaccine development and applications: A special focus on tumors (Review).

Cancer is characterized by unlimited proliferation and metastasis, and traditional therapeutic strategies usually result in the acquisition of drug resistance, thus highlighting the need for more personalized treatment. mRNA vaccines transfer the gene sequences of exogenous target antigens into human cells through transcription and translation to stimulate the body to produce specific immune responses against the encoded proteins, so as to enable the body to obtain immune protection against said antigens; this approach may be adopted for personalized cancer therapy. Since the recent coronaviru

BCL-2 and BCL-xL in Cancer: Regulation, Function, and Therapeutic Targeting.

The BCL-2 family of proteins plays a central role in the regulation of apoptosis, with BCL-2 and BCL-xL representing two of its most prominent antiapoptotic members. This review explores the molecular regulation of BCL-2 and BCL-xL genes, emphasizing the structural domains that define the functions of the broader BCL-2 family. Beyond their canonical roles in preventing mitochondrial outer membrane permeabilization, both proteins contribute significantly to cancer development. Their overexpression enhances invasiveness and tumor progression, supports angiogenesis, and critically modulates cellu

Совпадение в полном тексте источника
… A slower RNA polymerase II (RNAPII) rate of elongation can allow the repressor to bind to this region and induce BCL-xL production. …

Advances in antisense oligonucleotide development for target identification, validation, and as novel therapeutics.

Antisense oligonucleotides (As-ODNs) are single stranded, synthetically prepared strands of deoxynucleotide sequences, usually 18-21 nucleotides in length, complementary to the mRNA sequence of the target gene. As-ODNs are able to selectively bind cognate mRNA sequences by sequence-specific hybridization. This results in cleavage or disablement of the mRNA and, thus, inhibits the expression of the target gene. The specificity of the As approach is based on the probability that, in the human genome, any sequence longer than a minimal number of nucleotides (nt), 13 for RNA and 17 for DNA, normal

BCMA/CD19 CAR T cell therapy for refractory myasthenia gravis: Proteomic signatures and single-cell transcriptomics of disease flares.

Myasthenia gravis (MG) is an autoimmune disorder characterized by B cell dysfunction. Here, we designed B cell maturation antigen (BCMA)/CD19 chimeric antigen receptor T cell (CAR T cell) therapy for six refractory MGs, demonstrating favorable safety with grade 1 cytokine release syndrome observed. CAR T cell expansion induced profound B cell depletion, a sustained reduction in acetylcholine receptor (AChR) antibody titers, and symptom improvement. Five patients achieved drug-free remission with minimal manifestations by month 6, persisting through the 12-month follow-up despite B cell reconst

Non-Coding RNAs: The "Dark Side Matter" of the CLL Universe.

For many years in the field of onco-hematology much attention has been given to mutations in protein-coding genes or to genetic alterations, including large chromosomal losses or rearrangements. Despite this, biological and clinical needs in this sector remain unmet. Therefore, it is not surprising that recent studies have shifted from coded to non-coded matter. The discovery of non-coding RNAs (ncRNAs) has influenced several aspects related to the treatment of cancer. In particular, in chronic lymphocytic leukemia (CLL) the knowledge of ncRNAs and their contextualization have led to the ident

Sacubitril/Valsartan Ameliorates Crizotinib-Induced Cardiotoxicity in Mice.

BackgroundLung cancer is one of the major cause of death globally. Crizotinib is a first-line drug used in treating non-small-cell lung cancer (NSCLC). However, the pathophysiological mechanisms underlying its cardiotoxicity are unknown. This study investigated the mechanisms of crizotinib-induced cardiotoxicity and explored whether this toxicity can be prevented by the angiotensin receptor/neprilysin inhibitor sacubitril/valsartan.MethodsMale C57BL/6 mice were randomly divided into three groups: control, crizotinib (40 mg ⋅ kg - 1 ⋅ d - 1 for four weeks), and crizotinib + sacubitril/valsartan

The Application of Aptamer and Research Progress in Liver Disease.

Aptamers, as a kind of small-molecule nucleic acid, have attracted much attention since their discovery. Compared with biological reagents such as antibodies, aptamers have the advantages of small molecular weight, low immunogenicity, low cost, and easy modification. At present, aptamers are mainly used in disease biomarker discovery, disease diagnosis, treatment, and targeted drug delivery vectors. In the process of screening and optimizing aptamers, it is found that there are still many problems need to be solved such as the design of the library, optimization of screening conditions, the tr

Advances in Understanding Mitochondrial MicroRNAs (mitomiRs) on the Pathogenesis of Triple-Negative Breast Cancer (TNBC).

Triple-negative breast cancer (TNBC) is characterized by poor outcome and the most challenging breast cancer type to treat worldwide. TNBC manifests distinct profile of mitochondrial functions, which dictates reprogrammed metabolism, fosters tumor progression, and notably serves as therapeutic targets. Mitochondrial microRNAs (mitomiRs) are a group of microRNAs that critically modulate mitochondrial homeostasis. By a pathway-centric manner, mitomiRs tightly orchestrate metabolic reprogramming, redox status, cell apoptosis, mitochondrial dynamics, mitophagy, mitochondrial DNA (mtDNA) maintenanc

Совпадение в полном тексте источника
… As shown in Figure 1(b) , a miR gene is initially transcribed by RNA polymerase II into a primary miRNA (pri-miRNA) and then processed in the nucleus by microprocessor complex comprising an endoribonuclease Drosha and a double-stranded RNA-binding protein DiGeorge syndrome critical region 8 (DGCR8) into …

Целевые стратегии лечения рака цвета кожи: изучение использования аптемеров и золотых нанопчастей.

Рак цвета кожи (КЗК) является второй ведущей причиной смертности от рака и является причиной ~10% из всех случаев рака. По оценкам, во всем мире случаи, связанные с КПР 1.9 million и 930,000 смертями в 2022. Несмотря на расширение доступа к обследованиям и лечению в рамках КПР, ожидается, что показатели смертности резко возрастут в районах с низким уровнем ресурсов, что подчеркивает настоятельную необходимость принятия новаторских мер по лечению в рамках КПР. Текущая химиотерапия создает проблемы, такие, как плохая биодоступность, резистентность к многочисленным лекарствам и негативные побочны

Микроаэробный маленький белок от теплового шока способствует ризобию лимуминозараму/Писуму симбиозу и взаимодействует с широким диапазоном бактерироидных белков.

Во время создания симбиоза с бобовыми растениями ризобия подвергается воздействию враждебной физической и химической микроокружающей среды, к которой требуется адаптация. Протеины реакции на стресс, включая небольшие белки от теплового удара (SHSP), ранее, как было установлено, дифференцировались в бактерироидах, индуцируемых ризобием лимуминозарум бv. viciae UPM791 в различных хост-узлах. В ходе этой работы мы провели функциональный анализ зависящих от принимающей стороны SHSP RLV_1399. Рlv_1399- Исключенный штамм мутантов был нарушен в симбиотических свойствах гороха, но не чечевиц. Выражени

Identification of six hub genes and analysis of their correlation with drug sensitivity in acute myeloid leukemia through bioinformatics.

BackgroundAcute myeloid leukemia (AML) is a common hematopoietic malignancy and have unsatisfactory prognosis. Our study aimed to identify hub genes in AML and explore potential biomarkers through integrated bioinformatics.MethodsMicroarray datasets were analyzed to screen the differentially expressed genes (DEGs). Functional enrichment analysis was performed, and protein-protein interaction (PPI) network was generated by the STRING (11.0) database and Cytoscape (3.7.2) software. Hub genes were screened and verified through GEPIA2 and GEO microarray database. Sensitivity of AML cell lines with

Совпадение в полном тексте источника
… GO enrichment analysis revealed that changes in the most significant modules were mainly enriched in regulation of transcription from RNA polymerase II promoter, DNA-templated, cell proliferation and division. … Previous studies have reported that the dysregulation of transcription from RNA polymerase II promoter, cell proliferation, cell division and immune response play important roles in the carcinogenesis or progression of tumors ( 21 - 23 ). …

Telomerase-targeted therapies in myeloid malignancies.

Human telomeres are tandem arrays that are predominantly composed of 5'-TTAGGG-3' nucleotide sequences at the terminal ends of chromosomes. These sequences serve 2 primary functions: they preserve genomic integrity by protecting the ends of chromosomes, preventing inappropriate degradation by DNA repair mechanisms, and they prevent loss of genetic information during cellular division. When telomeres shorten to reach a critical length, termed the Hayflick limit, cell senescence or death is triggered. Telomerase is a key enzyme involved in synthesizing and maintaining the length of telomeres wit

Dysregulated TRK signalling is a therapeutic target in CYLD defective tumours.

Individuals with germline mutations in the tumour-suppressor gene CYLD are at high risk of developing disfiguring cutaneous appendageal tumours, the defining tumour being the highly organised cylindroma. Here, we analysed CYLD mutant tumour genomes by array comparative genomic hybridisation and gene expression microarray analysis. CYLD mutant tumours were characterised by an absence of copy-number aberrations apart from LOH chromosome 16q, the genomic location of the CYLD gene. Gene expression profiling of CYLD mutant tumours showed dysregulated tropomyosin kinase (TRK) signalling, with overex

Nucleotide Metabolism in Health and Disease.

Nucleotide metabolism is a fundamental biochemical process, providing the building blocks for DNA and RNA synthesis while driving critical cellular functions like energy transfer, signal transduction, and coenzyme synthesis. The precise regulation of nucleotide de novo synthesis, salvage, and degradation pathways is imperative for maintaining genomic stability and tissue homeostasis. Aberrations in these networks are increasingly recognized as primary drivers in various pathologies; notably, cancer cells exploit metabolic-functional reprogramming to enable rapid proliferation and therapeutic r

MSC Senescence-Related Genes Are Associated with Myeloma Prognosis and Lipid Metabolism-Mediated Resistance to Proteasome Inhibitors.

BackgroundComplex carcinogenic mechanisms and the existence of tumour heterogeneity in multiple myeloma (MM) prevent the most commonly used staging system from effectively interpreting the prognosis of patients. Since the microenvironment plays an important role in driving tumour development and MM occurs most often in middle-aged and elderly patients, we hypothesize that ageing of bone marrow mesenchymal stem cells (BM-MSCs) may be associated with the progression of MM.MethodsIn this study, we collected the transcriptome data on MM from The Cancer Genome Atlas (TCGA) and the Gene Expression O

Совпадение в полном тексте источника
… The main molecular functions (MFs) included voltage-gated sodium channel activation, sodium channel activity, catalytic-specific chromosome binding, and activation of RNA polymerase II-specificDNA-binding transcriptional activators ( Figure 3(a) ). …

NTRK Fusion in Non-Small Cell Lung Cancer: Diagnosis, Therapy, and TRK Inhibitor Resistance.

Neurotrophic tropomyosin receptor kinase (NTRK) gene fusion has been identified as an oncogenic driver of various solid tumors, and it is rare in non-smalll cell lung cancer (NSCLC) with a frequency of approximately less than 1%. Next-generation sequencing (NGS) is of priority for detecting NTRK fusions, especially RNA-based NGS. Currently, the tropomyosin receptor kinase (TRK) inhibitors have shown promising efficacy and well tolerance in patients with NTRK fusion-positive solid tumors, regardless of tumor histology. The first-generation TRK inhibitors (larotrectinib and entrectinib) are reco