Результаты поиска

Revealing G4 Structures as Drug Targets: Exploring the Potential of Novel Therapeutic Agents.

G-quadruplex (G4) structures represent noncanonical secondary formations found in DNA and RNA. Recent research reveals that G4s are abnormally enriched in various cancers, with closely linked to malignancy, metastatic potential, and prognosis. These structures have emerged as promising biomarkers for cancer with notable clinical relevance. Concurrently, investigations into compounds that selectively recognize DNA or RNA G4s as potential anticancer agents offer new avenues for early cancer diagnosis and therapeutic strategies. This review systematically analyzes the chemical structural characte

Совпадение в полном тексте источника
… For instance, in liposarcoma, the stabilization of a G4 conformation within the MDM2 promoter P2 region directly obstructs RNA polymerase II elongation and suppresses p53 degradation by silencing MDM2 transcription and subsequently apoptosis in cancer cells [ 94 ]. …

Структурный анализ признания35 Пропагандистский элемент SigW из Bacillus subtilis.

Сигма - это ключевые белки, которые служат посредником при наборе полимеразы РНК в стимулирующие области генов, для инициирования бактериальной транскрипции. Множественные сигма-факторы в бактерии избирательно распознают последовательности их когтевых промоутеров, тем самым вызывая выражение своих собственных регулонов. В настоящем документе мы сообщаем о кристаллической структуре4 Домена Bacillus subtilis SigW, связанная с...35 Пропаганда. Специфические водородные соединения:35 элемент стимулятора с спиралью распознавания α9 ЗАПЛАНИРОВАННЫЕ ЗАСЕДАНИЯ4 домена происходит на three нуклеотиды пос

Identification of broad anti-coronavirus chemical agents for repurposing against SARS-CoV-2 and variants of concern.

Endemic human coronaviruses (hCoVs) 229E and OC43 cause respiratory disease with recurrent infections, while severe acute respiratory syndrome (SARS)-CoV-2 spreads across the world with impact on health and societies. Here, we report an image-based multicycle infection procedure with α-coronavirus hCoV-229E-eGFP in an arrayed chemical library screen of 5440 clinical and preclinical compounds. Toxicity counter selection and challenge with the β-coronaviruses OC43 and SARS-CoV-2 in tissue culture and human airway epithelial explant cultures (HAEEC) identified four FDA-approved compounds with ora

COVID-19 Therapeutic Options Under Investigation.

Since its emergence in China in December 2019, COVID-19 has quickly spread around the globe causing a pandemic. Vaccination or the development of herd immunity seems the only way to slow down the spread of the virus; however, both are not achievable in the near future. Therefore, effective treatments to mitigate the burden of this pandemic and reduce mortality rates are urgently needed. Preclinical and clinical studies of potential antiviral and immunomodulatory compounds and molecules to identify safe and efficacious therapeutics for COVID-19 are ongoing. Two compounds, remdesivir, and dexame

Bortezomib inhibits chikungunya virus replication by interfering with viral protein synthesis.

Chikungunya virus (CHIKV) is an alphavirus that causes a febrile illness accompanied by myalgia and arthralgia. Despite having re-emerged as a significant public health threat, there are no approved therapeutics or prophylactics for CHIKV infection. In this study, we explored the anti-CHIKV effects of proteasome inhibitors and their potential mechanism of antiviral action. A panel of proteasome inhibitors with different functional groups reduced CHIKV infectious titers in a dose-dependent manner. Bortezomib, which has been FDA-approved for multiple myeloma and mantle cell lymphoma, was further

Совпадение в полном тексте источника
… Another example is RpbI, a catalytic subunit of RNA polymerase II. Recently, Akhrymuk and colleagues reported that the nsP2 of CHIKV, SINV and SFV induce the shut-off of host transcription by causing the proteasomal degradation of RpbI [ 53 ]. … Evasion of the innate immune response: the Old World alphavirus nsP2 protein induces rapid degradation of Rpb1, a catalytic subunit of RNA polymerase II. J Virol. 2012;86(13):7180–91. 10.1128/JVI.00541-12 54. Varjak M, Zusinaite E, Merits A. …

The important role of the histone acetyltransferases p300/CBP in cancer and the promising anticancer effects of p300/CBP inhibitors.

Histone acetyltransferases p300 (E1A-associated protein p300) and CBP (CREB binding protein), collectively known as p300/CBP due to shared sequence and functional synergy, catalyze histone H3K27 acetylation and consequently induce gene transcription. p300/CBP over-expression or over-activity activates the transcription of oncogenes, leading to cancer cell growth, resistance to apoptosis, tumor initiation and development. The discovery of small molecule inhibitors targeting p300/CBP histone acetyltransferase activity, bromodomains, dual inhibitors of p300/CBP and BRD4 bromodomains, as well as p

Совпадение в полном тексте источника
… Introduction RNA polymerases II (RNA Pol II) catalyses gene transcription to generate message RNAs (mRNAs) (Girbig et al. 2022 ). … Structure and mechanism of the RNA polymerase II transcription machinery. …

The Role of Nucleotide Excision Repair in Cisplatin-Induced Peripheral Neuropathy: Mechanism, Prevention, and Treatment.

Platinum-based chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common dose-limiting effects of cancer treatment and results in dose reduction and discontinuation of life-saving chemotherapy. Its debilitating effects are often permanent and lead to lifelong impairment of quality of life in cancer patients. While the mechanisms underlying the toxicity are not yet fully defined, dorsal root ganglia sensory neurons play an integral role in symptom development. DNA-platinum adducts accumulate in these cells and inhibit normal cellular function. Nucleotide excision repair (NER)

Совпадение в полном тексте источника
… The DNA lesion, as indicated by the red star, stalls transcription by RNA polymerase II (RNA pol II). UVSSA and USP7 stabilize and form a complex with CSB. CSA binds to CSB, likely resulting in backward translocation of RNA pol II and allowing room for NER machinery. …

Инсило-исследования для понимания взаимодействий флавонового ингибитора с nsp12-РНК-зависимой РНК-полимеразой SARS-CoV-2 и его гомологами.

Цель. ВИРУС COVID-19 продолжает быть важной проблемой здравоохранения. РНК-зависимый РНК-полимераза (RdRp) SARS-CoV-2, которая критична для репликации, поэтому является потенциальным объектом для лекарственной терапии. Методология. На основе экспериментальных структур RdRp от SARS-CoV-2 были сгенерированы вычислительные модели его гомологов от SARS-CoV-1, MERS и летучих мышей. SARS-CoV-2 RdRp был использован для виртуального скрининга в нуклеотидном связывающем сайте с молекулами из базы данных COCONUT Natural Products с помощью Glide. Комплексы с верхней ингибиторной молекулой были смоделиров

Multiple myeloma: clinical characteristics, current therapies and emerging innovative treatments targeting ribosome biogenesis dynamics.

Multiple myeloma (MM) is a clinical disorder characterized by aberrant plasma cell growth in the bone marrow microenvironment. Globally, the prevalence of MM has been steadily increasing at an alarming rate. In the United States, more than 30,000 cases will be diagnosed in 2024 and it accounts for about 2% of cancer diagnoses and more than 2% of cancer deaths, more than double the worldwide figure. Both symptomatic and active MM are distinguished by uncontrolled plasma cell growth, which results in severe renal impairment, anemia, hypercalcemia, and bone loss. Multiple drugs have been approved

Структурно-ориентированное понимание специфичности 2ДГ-III реберосчег.

Рибосчемы сохраняют некодированные домена РНК, в основном расположенные на 5'-конец бактериальных MRNA, которые служат регулятором генного экспрессии. Недавно третий класс 2Дексигуанозин реберосколка.2'-dG-III) был идентифицирован из семейства рибоколдов, проявляющих сопоставимую связь с 2ДиДжи, Гунанин и гуанозин. Чтобы прояснить уникальный механизм распознавания лиганда, мы раскрыли его кристаллы в комплексе с различными производными пурины, включая 2ДиДжи, Гунанин и гуанозин. Трехсторонняя структура показывает типичную архитектуру, похожую на вилку, с three вырезки, соединяющиеся в центре t

Non-Exosomal and Exosomal Circulatory MicroRNAs: Which Are More Valid as Biomarkers?

MicroRNAs (miRNAs) are a group of small non-coding RNAs with approximately 19-25 nucleotides that are involved in regulating a range of developmental and physiological processes. Non-exosomal circulating and exosomal miRNAs have also been proposed to be useful in diagnostics as biomarkers for diseases and different types of cancer. In this review, the quantity of miRNAs and of reliable experimental data analyses of miRNAs that come from exosomal and non-exosomal sources are discussed from the perspective of their use as biomarkers for cancer and other diseases, including viral infections, nerv

A review of feline infectious peritonitis virus infection.

Feline infectious peritonitis (FIP) is an infectious disease characterized by non-specific laboratory changes and clinical signs. Clinical symptoms include anorexia, jaundice, fever, and weight loss. Moreover, some lesions are found in the digestive and respiratory systems. FIP, whose virulence varies, cannot be distinguished using several diagnostic methods. Moreover, feline coronaviruses (FCoVs) can be classified into two serotypes based on differences in their amino acid sequences, spike (S) protein sequences, and antibody (Ab) neutralization. There are two pathotypes, namely those caused b

Emerging therapeutics in the management of COVID-19.

The severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019, COVID-19) pandemic has placed a tremendous burden on healthcare systems globally. Therapeutics for treatment of the virus are extremely inconsistent due to the lack of time evaluating drug efficacy in clinical trials. Currently, there is a deficiency of published literature that comprehensively discusses all therapeutics being considered for the treatment of COVID-19. A review of the literature was performed for articles related to therapeutics and clinical trials in the context of the current COVID-19 pandemic. We

Molecular Targeting and Rational Chemotherapy in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a molecularly complex disease with multiple aberrant genetic pathways involved in its pathogenesis. Approximately one-third to one-half of patients with AML would relapse, and no standard therapy is established for relapsing and/or refractory AML (RR-AML) yet. It is unlikely that blockage of only one specific pathway will lead to prolonged remissions and cures in all fractions of the AML patients population. Nowadays, novel therapeutic agents with rational combination are being recognized which improve the cure rate for relapsed AML. These drugs and their metabo

The novel role of circular RNA ST3GAL6 on blocking gastric cancer malignant behaviours through autophagy regulated by the FOXP2/MET/mTOR axis.

Gastric cancer (GC) ranks third in mortality among all cancers worldwide. Circular RNAs (circRNAs) play an important role in the occurrence and development of gastric cancer. Forkhead box P2 (FOXP2), as a transcription factor, is closely associated with the development of many types of tumours. However, the regulatory network between FOXP2 and circRNAs remains to be explored. In our study, circST3GAL6 was significantly downregulated in GC and was associated with poor prognosis in GC patients. Overexpression of circST3GAL6 inhibited the malignant behaviours of GC cells, which was mediated by in

Усовершенствованные испытания самообслуживания в системном склерозе

Системный склероз — это системное аутоиммунное ревматическое заболевание, характеризующееся иммунными аномалиями, приводящее к васкулопатии и фиброзу. Тестирование самодисциплины становится все более важной частью диагностики и прогнозирования. Клинические врачи были ограничены антиядерной антителной (АНА), антитопоизомеразой I (также известной как anti-Scl-70) антитела и антисентромерные антитела. Многие врачи в настоящее время улучшили доступ к расширенному профилю автоантиорганических тестов. В этой статье мы анализируем эпидемиологию, клинические ассоциации и предсказанную ценность совреме

Feline infectious peritonitis.

The article discusses feline infectious peritonitis (FIP), an important disease frequently seen in veterinary practice. FIP causes many problems to the veterinarian as it can be difficult to definitively diagnose the disease, as there is no effective treatment, and as prophylactic interventions are not very successful. Although intense research has created a lot of new knowledge about this disease in the last years, there are still many unanswered questions. The objective of this article is to review recent knowledge and to increase understanding of the complex pathogenesis of FIP.

The crosstalk network of non-coding RNAs: Emerging opportunities for the clinical application of osteoporosis.

Current methods for testing bone density lack the capability to detect patients with early bone loss, and existing osteoporosis therapies have limitations in their efficacy and safety. Therefore, the development of more precise and convenient diagnostic technologies and novel treatments is of paramount importance. Extracellular vesicle (EV)-mediated non-coding RNA (ncRNA) interaction networks enable both the detection of early bone loss and targeted therapy for enhanced treatment outcomes. In this review, we highlight the utility of EVs for carrying various ncRNAs (e.g., miRNAs, lncRNAs, and c

Совпадение в полном тексте источника
… polymerase II (RNA Pol II) into pri-miRNAs, which have complex secondary structures ranging in length from several hundred to several thousand nucleotides. … RNA polymerase II transcribes long single-stranded RNA precursors, which are then processed into mature piRNAs through a complex process (mainly through the ping-pong cycle). The mature piRNA binds to PIWI proteins to form the piRISC complex to exert its function. …

Next generation sequencing: new tools in immunology and hematology.

One of the hallmarks of the adaptive immune system is the specificity of B and T cell receptors. Thanks to somatic recombination, a large repertoire of receptors can be generated within an individual that guarantee the recognition of a vast number of antigens. Monoclonal antibodies have limited applicability, given the high degree of diversity among these receptors, in BCR and TCR monitoring. Furthermore, with regard to cancer, better characterization of complex genomes and the ability to monitor tumor-specific cryptic mutations or translocations are needed to develop better tailored therapies

Совпадение в полном тексте источника
… Additionally, by ontology analysis, they identified "negative regulation of transcription from RNA polymerase II," suggesting the potential presence of a feedback loop, in which specific miRNAs and transcription factors regulate their own expression by 2 pathways, depending on MDS grade: by enhancing …

miRNA-seq identification and clinical validation of CD138+ and circulating miR-25 in treatment response of multiple myeloma.

BackgroundDespite significant advancements in multiple myeloma (MM) therapy, the highly heterogenous treatment response hinders reliable prognosis and tailored therapeutics. Herein, we have studied the clinical utility of miRNAs in ameliorating patients' management.MethodsmiRNA-seq was performed in bone marrow CD138+ plasma cells (PCs) of 24 MM and smoldering MM (sMM) patients to analyze miRNAs profile. CD138+ and circulating miR-25 levels were quantified using in house RT-qPCR assays in our screening MM/sMM cohort (CD138+ plasma cells n = 167; subcohort of MM peripheral plasma samples n = 69)