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Beyond Vaccines: Clinical Status of Prospective COVID-19 Therapeutics.

Since November 2019 the SARS-CoV-2 pandemic has caused nearly 200 million infection and more than 4 million deaths globally (Updated information from the World Health Organization, as on 2nd Aug 2021). Within only one year into the pandemic, several vaccines were designed and reached approval for the immunization of the world population. The remarkable protective effects of the manufactured vaccines are demonstrated in countries with high vaccination rates, such as Israel and UK. However, limited production capacities, poor distribution infrastructures and political hesitations still hamper th

Идентификация и проверка генов, связанных со старением, у пациентов с множественной миеломой.

Это исследование было направлено на выявление и проверку связанных со старением генов (ARGs), связанных с множественной миеломой (MM), что способствовало более глубокому пониманию молекулярных механизмов, лежащих в основе этого заболевания. Для изучения функциональных ролей ARG в MM были проведены генной онтологии и Киото-Энциклопедии по обогащению генов и геномов. Потенциальные гены, выявленные с помощью наименьшего абсолютного сокращения и селекционного оператора (LASSO) логистической регрессии и рекурсивного устранения векторных функций (SVM-RFE), были сопоставлены с помощью диаграммы Венна

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… The most significant GO enrichment terms included the ‘positive regulation of miRNA transcription’, ‘regulation of miRNA transcription’ (biological process), ‘RNA polymerase II transcription regulator complex’, ‘high-density lipoprotein particle’, ‘plasma lipoprotein particle’ (cellular component), ‘ … DNA-binding transcription factor binding’, ‘RNA polymerase II-specific DNA-binding transcription factor binding’ and ‘transcription co-regulator binding’ (molecular function) ( Fig. 3A ). …

Расположение RNA на основе RiboTag обнаруживает олигодендроглиевую воспаление в аутоиммунном энцефаломиелите: последствия для патогенеза.

Клетки олигодендроглиевой линии (ООК) необходимы для миелинирования, ремиелиции и нейронной метаболической поддержки, но недавние данные указывают на то, что они также играют активную роль в нейроинфламмации. Цель этого исследования состояла в том, чтобы выявить подстрекательский транслатом ОРЦ в начале экспериментального аутоиммунного энцефаломиэлита (EAE) - широко используемой модели множественного склероза (MS) с использованием последовательности РНК на основе RNA, основанной на RiboTag. Мы пересекли мышей Риботага Olig2-Cre Мыши для получения экспресс-выражения реберосомного белка HA-тагон

Circulating Exosomal CircMYC Is Associated with Recurrence and Bortezomib Resistance in Patients with Multiple Myeloma

ObjectiveStudies have shown that serum circRNA can be used as a biomarker for many tumors. However, the role of exosomal circRNA in prognostic evaluation in patients with multiple myeloma (MM) remains unclear. In this study, we aimed to analyze the role of circulating exosomal circMYC in the relapse and prognosis of patients with MM.Materials and methodsCirculating exosomes from 122 patients with MM and 54 healthy people were isolated. Quantitative polymerase chain reaction was performed to measure circMYC exosomal expression. Kaplan-Meier survival curves with log-rank testing were used for es

Targeting BRD4: Potential therapeutic strategy for head and neck squamous cell carcinoma (Review).

As a member of BET (bromodomain and extra-terminal) protein family, BRD4 (bromodomain‑containing protein 4) is a chromatin‑associated protein that interacts with acetylated histones and actively recruits regulatory proteins, leading to the modulation of gene expression and chromatin remodeling. The cellular and epigenetic functions of BRD4 implicate normal development, fibrosis and inflammation. BRD4 has been suggested as a potential therapeutic target as it is often overexpressed and plays a critical role in regulating gene expression programs that drive tumor cell proliferation, survival, mi

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… The perturbed chromatin structure and nucleosome remodeling at the promoters allow transcription factors as well as RNA Polymerase II to enter and start the transcription process ( 18 ). … Furthermore, BRD4 coupling with RNA Polymerase II complex assists the complex to elongate through hyperacetylated nucleosomes by interacting with acetylated histones using bromodomains ( 19 ). …

Coronavirus Disease (COVID-19) Control between Drug Repurposing and Vaccination: A Comprehensive Overview.

Respiratory viruses represent a major public health concern, as they are highly mutated, resulting in new strains emerging with high pathogenicity. Currently, the world is suffering from the newly evolving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus is the cause of coronavirus disease 2019 (COVID-19), a mild-to-severe respiratory tract infection with frequent ability to give rise to fatal pneumonia in humans. The overwhelming outbreak of SARS-CoV-2 continues to unfold all over the world, urging scientists to put an end to this global pandemic through biological and

Tumor-educated leukocytes mRNA as a diagnostic biomarker for non-small cell lung cancer.

BackgroundThis study aimed to investigate the diagnostic and prognostic role of tumor-educated leukocytes (TELs) mRNA in Chinese patients with non-small cell lung cancer (NSCLC).MethodsThe TELs collected underwent total RNA isolation. RNA-sequencing (RNA-seq) technology was used to analyze the transcriptome of the TELs. The mRNA expression levels of differential genes were analyzed by RT-qPCR. Statistical analyses were performed using Prism and SPSS by Mann-Whitney nonparametric test, Kruskal-Wallis test and one-way ANOVA.ResultsWe used RNA-seq technology to screen 95 differential genes (DEGs)

Spiegelmer Aptamers: Innovative Approach in Breast Cancer.

Breast cancer remains one of the leading causes of cancer-related mortality among women worldwide, emphasizing the urgent need for improved diagnostic and therapeutic strategies. Aptamers which are synthetic oligonucleotides that specifically bind to target molecules, offer high affinity, low immunogenicity, and superior tumor penetration compared to antibodies. However, their clinical translation has been limited by instability in biological systems. Spiegelmers, a novel class of mirror-image aptamers composed of L-nucleotides, overcome this limitation through intrinsic nuclease resistance an

PRMT inhibitor promotes SMN2 exon 7 inclusion and synergizes with nusinersen to rescue SMA mice.

Spinal muscular atrophy (SMA) is a leading genetic cause of infant mortality. The advent of approved treatments for this devastating condition has significantly changed SMA patients' life expectancy and quality of life. Nevertheless, these are not without limitations, and research efforts are underway to develop new approaches for improved and long-lasting benefits for patients. Protein arginine methyltransferases (PRMTs) are emerging as druggable epigenetic targets, with several small-molecule PRMT inhibitors already in clinical trials. From a screen of epigenetic molecules, we have identifie

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… A recent study has shown that nusinersen, while promoting exon 7 inclusion, also induces a silencing histone mark H3K9me2 on SMN2 gene, creating a roadblock to RNA polymerase II elongation. … Nat Rev Cancer 13: 37–50 Yanling Zhao D, Gish G, Braunschweig U, Li Y, Ni Z, Schmitges FW, Zhong G, Liu K, Li W, Moffat J et al (2016) SMN and symmetric arginine dimethylation of RNA polymerase II C‐terminal domain control termination. …

Beyond regulations at DNA levels: A review of epigenetic therapeutics targeting cancer stem cells.

In the past few years, the paramount role of cancer stem cells (CSCs), in terms of cancer initiation, proliferation, metastasis, invasion and chemoresistance, has been revealed by accumulating studies. However, this level of cellular plasticity cannot be entirely explained by genetic mutations. Research on epigenetic modifications as a complementary explanation for the properties of CSCs has been increasing over the past several years. Notably, therapeutic strategies are currently being developed in an effort to reverse aberrant epigenetic alterations using specific chemical inhibitors. In thi

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… FIGURE 2 The miRNA biogenesis begins with their transcription by RNA polymerase II which produces primary miRNA (pri‐miRNA) as an end product. … For example, circ‐PAIP2 and circ‐EIF3J are reportedly combined with RNA polymerase II complex and translation‐related proteins, resulting in the increased expression of EIF3J and PAIP2 91 , 92 ; (3) translating proteins. …

Inhibition of CARM1 suppresses proliferation of multiple myeloma cells through activation of p53 signaling pathway.

BackgroundMultiple myeloma (MM) is a malignant proliferative disease of plasma cells, the incidence of which is increasing every year and remains incurable. The enzyme co-activator-associated arginine methyltransferase 1 (CARM1) is highly expressed in a variety of cancers, such as Hodgkin's lymphoma and acute myeloid leukemia, and CARM1 is closely associated with tumor cell proliferation. However, the role of CARM1 in MM has not been elucidated.Methods and resultsIn this study, we found that CARM1 is overexpressed in MM and closely associated with poor prognosis in MM. CCK-8 and colony formati

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… In addition, Fig. 4 E shows that CARM1 can negative regulation of transcription by RNA polymerase II and protein binding, indicating that CARM1 might negatively regulate the transcription of p53 by binding transcription factors. …

A review of potential suggested drugs for coronavirus disease (COVID-19) treatment.

The latest pandemic, coronavirus disease-2019 (COVID-19), is associated with high prevalence and easy transmission, which is expanding globally with no conventional treatment or vaccine. The new virus revealed 79% and 50% genomic similarities with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), respectively. Accordingly, since the disease resists testing and adopting new therapeutics, repositioning pre-existing drugs may present a fast and attractive strategy with known safety, characteristics, and dosage used. However, they

Bioinformatics Analysis of the Key Genes and Pathways in Multiple Myeloma.

ObjectiveTo study the differentially expressed genes between multiple myeloma and healthy whole blood samples by bioinformatics analysis, find out the key genes involved in the occurrence, development and prognosis of multiple myeloma, and analyze and predict their functions.MethodsThe gene chip data GSE146649 was downloaded from the GEO expression database. The gene chip data GSE146649 was analyzed by R language to obtain the genes with different expression in multiple myeloma and healthy samples, and the cluster analysis heat map was constructed. At the same time, the protein-protein interac

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… In GO analysis ( Figure 3 ), biological process (BP) is mainly enriched in transcription regulation, cell adhesion and cell differentiation of RNA polymerase II promoter. Cellular components (CC) are mainly extracellular exosomes, cytoplasm, cytoplasmic membrane, etc. … In GO analysis, DEG is mainly enriched in the transcription regulation, cell adhesion, cell differentiation of RNA polymerase II promoter, significant enrichment in protein binding rate, cell adhesion is the key to the spread and progress of multiple myeloma. …

РНК-Сек, базирующаяся на RNA-Seq, обнаруживает воспаление олигодендроглиевой линии в аутоиммунном энцефаломиелите.

Клетки олигодендроглиевой линии (ООК) имеют решающее значение для нейронных функций поддержки, включая минелинирование и воспоминание. Появляющиеся данные свидетельствуют об их активной роли в нейроинфламмации, особенно в таких условиях, как Множественный склероз (MS). В рамках этого исследования изучается возбудительный транслатом ОРЦ в начале экспериментального аутоиммунного энцефаломиелита (EAE), который представляет собой установленную модель НР. Использование последовательности РНК на основе RiboTag в генетически модифицированных системах Olig2-Cre Мыши RiboTag, мы опознали 1,556 Регулиру

Investigation of Some Long Noncoding RNAs (LncRNAs) in Pediatric Inflammatory Bowel Disease (IBD): An Iranian Study.

Introduction: According to the importance of long noncoding RNAs (LncRNA) in the pathogenesis of inflammatory bowel disease (IBD) and also the lack of study for pediatric IBD in this regard, we investigated the expression of a selected panel of LncRNAs in Iranian pediatric cases of IBD compared to adult cases and healthy samples. Methods: In this gene expression study, blood samples were taken from the three groups of pediatric IBD cases, adult IBD cases, and pediatric healthy samples (for gene expression calibration). The investigated LncRNAs were UCA1, CCAT, IFNG-AS1, and CDKN2B. Real-time P

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… LncRNAs, like mRNAs, are transcribed by RNA polymerase II, and after transcription, capping and polyadenylation processes occur in them [ 2 – 4 ]. …

Премии победителей и резюме 32nd Ежегодный симпозиум Общества протеинов; Бостон, ОЭТ, июль 9-12, 2018.

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Clinical outcomes of chemotherapy in cancer patients with different ethnicities.

BackgroundChoosing the most effective chemotherapeutic agent with safest side effect profile is a common challenge in cancer treatment. Although there are standardized chemotherapy protocols in place, protocol changes made after extensive clinical trials demonstrate significant improvement in the efficacy and tolerability of certain drugs. The pharmacokinetics, pharmacodynamics, and tolerance of anti-cancer medications are all highly individualized. A driving force behind these differences lies within a person's genetic makeup.Recent findingsPharmacogenomics, the study of how an individual's g

Boron Chemicals in Drug Discovery and Development: Synthesis and Medicinal Perspective.

A standard goal of medicinal chemists has been to discover efficient and potent drug candidates with specific enzyme-inhibitor abilities. In this regard, boron-based bioactive compounds have provided amphiphilic properties to facilitate interaction with protein targets. Indeed, the spectrum of boron-based entities as drug candidates against many diseases has grown tremendously since the first clinically tested boron-based drug, Velcade. In this review, we collectively represent the current boron-containing drug candidates, boron-containing retinoids, benzoxaboroles, aminoboronic acid, carboran

Нацеливание moTOR сигнализирующих путей в нескольких миеломах: биология и последствия для терапии.

Множественная миелома (ММ), рак неизлечимо дифференцированных плазменных клеток, является вторым по распространенности гематологической злокачественности и неизлечимо из-за неизбежного развития лекарственной устойчивости. Интенсивный синтез белка является отличительной чертой клеток MM, поддерживающей массовое производство клональных иммуноглобулинов или свободных световых цепей. Млекопитающая цель рэпамицин (mTR) киназы ценится как главный регулятор жизненно важных клеточных процессов, включая регулирование метаболизма и синтеза белка, и может быть найдена в two Мультипротеиновые комплексы, M

Осколки периферальной крови, полученные в результате ТРНК, являются новыми неинвазивными биомаркерами для диагностики и прогнозируемой стратификации в множестве миеломы.

В последнее время в качестве критически важных регуляторов в области онкологической биологии появились небольшие РНК, полученные в результате передачи РНК; однако их профили экспрессии и клиническая значимость в нескольких миеломах (ММ) по-прежнему плохо определены. МЕТОДЫ: Секвенирование высокой производительности было проведено для всеобъемлющей характеристики профилей выражения ТСНК в периферийных моноядерных клетках крови (ПБМК) из 22 новые пациенты с диагнозом MM и 19 здоровый контроль. Общие целевые гены были предсказаны путем интеграции MiRanda и TookScan, и была создана сеть взаимодейс

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… The BPs demonstrated enrichment for “regulation of nitrogen compound metabolic process” (GO:0051171), “regulation of primary metabolic process” (GO:0080090), “cellular component organization or biogenesis” (GO:0071840), “cellular component organization” (GO:0016043), “transcription by RNA polymerase … II” (GO:0006351) and “regulation of transcription by RNA polymerase II” (GO:0006366), indicating the target genes were primarily involved in critical processes such as nitrogen compound metabolism, RNA polymerase II transcription, and ribosome biogenesis, which reflects their central role in the regulation …