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Novel insights into the phylogenetic and metabolic diversity of preussia-like fungi.

The genus Preussia (Sporormiaceae, Pleosporales) represents one of the most diverse and metabolically active groups of ascomycetes. The genu … (LSU) nrDNA. Additional regions within protein-encoding genes were used, including the DNA-directed RNA polymerase II second-largest subunit (rpb2) and translation elongation factor 1-α (tef1-α) regions. These data were used to reconstruct a robust phylogenetic framework for Preussia s.l. and to delineate lineage structure and generic boundaries. Ten well-supported …

Effect of the Shensong Yangxin Capsule on Energy Metabolism in Angiotensin II-Induced Cardiac Hypertrophy.

BACKGROUND: Shensong Yangxin Capsule (SSYX), traditional Chinese medicine, has been used to treat arrhythmias, angina, cardiac remodeling, cardiac fibrosis, and so on, but its effect on cardiac energy metabolism is still not clear. The objective of this study was to investigate the effects of SSYX on myocardium energy metabolism in angiotensin (Ang) II-induced cardiac hypertrophy. METHODS: We used 2 μl (10-6 mol/L) AngII to treat neonatal rat cardiomyocytes (NRCMs) for 48 h. Myocardial α-actinin staining showed that the myocardial cell volume increased. Expression of the cardiac hypertrophic

Effects of traditional chinese medicine on endotoxin and its receptors in rats with non-alcoholic steatohepatitis.

AIMS: The aim of this research is to study the effects of traditional Chinese medicine on endotoxin and its receptors in rats with nonalcoholic steatohepatitis (NASH). METHODS: Fifty-six SD rats were divided into seven groups. All the animals were fed high fatty diet for 12 weeks. Rats with non-alcoholic steatohepatitis (NASH) were treated with traditional Chinese medicine according to low-dose, middle-dose, high-dose and Lipitor from fifth week. All rats were killed at the end of 12th week. The liver pathology changes were observed under light microscope. The levels of serum lipoid, alanine

Effect of TGF-β on ocular surface epithelial cells.

A role for transforming growth factor (TGF)-β in the pathogenesis of some ocular surface diseases has been proposed. We determined if secretion of TGF-β and expression of TGF-β receptors RI, RII, and RIII by human ocular surface epithelial cells were modified under inflammatory conditions. We also determined how these cells responded to TGF-β. A human corneal epithelial (HCE) cell line and a conjunctival epithelial cell line (IOBA-NHC) were exposed to TGF-β1 and -β2 and to proinflammatory cytokines. TGF-β receptor mRNAs were analyzed by real time reverse transcription polymerase chain reaction

Current and future role of genetic screening in gynecologic malignancies.

The world of hereditary cancers has seen exponential growth in recent years. While hereditary breast and ovarian cancer and Lynch syndrome account for the majority of mutations encountered by gynecologists, newly identified deleterious genetic mutations continue to be unearthed with their associated risks of malignancies. However, these advances in genetic cancer predispositions then force practitioners and their patients to confront the uncertainties of these less commonly identified mutations and the fact that there is limited evidence to guide them in expected cancer risk and appropriate ri

The IGF system in the neonatal ovine uterus.

Postnatal development of the ovine uterus primarily involves uterine gland morphogenesis or adenogenesis. Adenogenesis involves the budding differentiation of the glandular epithelium (GE) from the luminal epithelium (LE) and then GE proliferation and coiling/branching morphogenetic development within the stroma between birth (postnatal day or PND 0) and PND 56. Insulin-like growth factor (IGF)-I and IGF-II mRNAs were previously found to be expressed only in the endometrial stroma, whereas the IGF receptor (IGF-1R) mRNA was most abundant in epithelia and in stroma, suggesting that an intrinsic

Overexpression of miR-142-3p improves mitochondrial function in cardiac hypertrophy.

BACKGROUND AND PURPOSE: Our previous studies have shown that Src homology 2 (SH2) B adaptor protein 1 (SH2B1) plays an important role in cardiac hypertrophy, but the specific mechanism remains to be studied. Through bioinformatics and related research, it is found that miR-14 2-3 p is closely related to SH2B1. Exploring the relationship between miR-14 2-3 p and gene SH2B1 expression is beneficial for the treatment of cardiac hypertrophy. SH2B1 is a key factor regulating energy metabolism, mitochondria are the main organelles of energy metabolism and cardiac hypertrophy are closely related to m

Expression of TNF receptors and related signaling molecules in the bone marrow from patients with myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are characterized by peripheral blood cytopenias despite hypercellularity of the bone marrow regarded as the result of ineffective hematopoiesis mainly caused by apoptosis. In this study, we examined the role of tumor necrosis factor (TNF)-induced apoptosis in the bone marrow cells of MDS patients. The constitutive expression of mRNA for TNF receptors (TNFR), including TNFRI and TNFRII, and the adapter molecules, such as the TNF receptor-associated death domain protein (TRADD), Fas-associated death domain protein (FADD), receptor interacting protein (RIP) and TN

Activated pulmonary macrophages are insufficient for resistance against Pneumocystis carinii.

CD4+ T cells are pivotal for elimination of Pneumocystis carinii from infected lungs, and alveolar macrophages are considered the main effector cells clearing the infected host of P. carinii organisms. To investigate this issue, several mutant mouse strains were used in a previously established experimental setup which facilitates natural acquisition of disease through inhalation of airborne fungal organisms. Mutant mice deficient in major histocompatibility complex class II molecules (A beta(-/-)), T-cell receptor alphabeta cells (TCR beta(-/-)), or all mature T and B lymphocytes (RAG-1(-/-))

Expressions of topoisomerase IIα and BCRP in metastatic cells are associated with overall survival in small cell lung cancer patients.

The aim of this study was to investigate the mRNA expression levels of multidrug resistance-associated proteins in chemo-naïve metastatic lung cancer cells and to determine the correlation with response to chemotherapy and overall survival. Metastatic cells were obtained by transbronchial fine needle aspiration biopsy of enlarged mediastinal lymph nodes in 14 patients with small cell lung cancer (SCLC) and 7 patients with non-small cell lung cancer (NSCLC). After cytological confirmation of lung cancer type, total RNA was extracted from biopsy samples and reverse transcribed to cDNA, and real-

Lost in transcription: molecular mechanisms that control HIV latency.

Highly active antiretroviral therapy (HAART) has limited the replication and spread of the human immunodeficiency virus (HIV). However, despite treatment, HIV infection persists in latently infected reservoirs, and once therapy is interrupted, viral replication rebounds quickly. Extensive efforts are being directed at eliminating these cell reservoirs. This feat can be achieved by reactivating latent HIV while administering drugs that prevent new rounds of infection and allow the immune system to clear the virus. However, current approaches to HIV eradication have not been effective. Moreover,

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… Gene–specific RNA polymerase II phosphorylation and the CTD code Nat. Struct. Mol. Biol. 2010 17 1279 1286 10.1038/nsmb.1913 20835241 PMC3048030 32. Lenasi T. Peterlin B.M. Dovc P. … Promoter–proximal pausing of RNA polymerase II: emerging roles in metazoans Nat. Rev. Genet. 2012 13 720 731 10.1038/nrg3293 22986266 PMC3552498 57. Core L.J. Lis J.T. …

Структурная основа регламентации стенограмм с помощью нарождающегося элемента РНК, HK022 potRNA.

Переписка, в которой RNA полимеразы (RNAPs) производят RNA из ДНК, является первым шагом в генной экспрессии. Таким образом, она сильно регулируется либо трансэлементами, такими как белковые факторы, и/или резьбами, как конкретные последовательности на ДНК. В лямбдоидной фаге HK022 содержится резьбовое пятно, которое подавляет падение и прекращение во время транскрипции ранних фаговых генов. Протокол PotRNA осуществляет исключительно деятельность по борьбе с растлением/прекращением путем прямого взаимодействия с комплексом удлинения RNA E.coli (EC) с помощью неизвестного структурного механизма

Transcription and Translation Inhibitors in Cancer Treatment.

Transcription and translation are fundamental cellular processes that govern the protein production of cells. These processes are generally up regulated in cancer cells, to maintain the enhanced metabolism and proliferative state of these cells. As such cancerous cells can be susceptible to transcription and translation inhibitors. There are numerous druggable proteins involved in transcription and translation which make lucrative targets for cancer drug development. In addition to proteins, recent years have shown that the "undruggable" transcription factors and RNA molecules can also be targ

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… Pol II, RNA polymerase II; TFIID, transcription factor IID; CDK, cyclin dependent kinase. Transcription of genes starts with the binding of transcription factor II D (TFIID) to the core promoter of the gene (Patel et al., 2020 ). … There it starts the assembly of the large pre-initiation complex (PIC), which includes various transcription factors, cofactors, RNA polymerase II (Pol II), TFIIH and Mediator complexes. …

" Nucleolus in Human Beasons: Ribosome Biogenesis " , " Nucleolar Survey " и " Terrapeutic Opportunities " .

Nucleolus превратился в динамичную и многофункциональную субядерную органилию, интегрирующую рибосомный биогенез с клеточным ростом и сигнализацией стресса. Регулирование нуклеолярной функции все чаще признается в качестве главного движителя человеческих заболеваний, связывающего изменённое рибосомное производство и нуклеолярное наблюдение с раком, рибосомопатиями, синдромами преждевременного старения, нейродегенерацией и иммунными расстройствами. В этом обзоре мы интегрируем структурные, молекулярные и болезнетворные перспективы нуклеолярной биологии для определения того, как рипосомный биоге

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… Genes encoding ribosomal proteins (RPs) and RiBi factors are transcribed by RNA Polymerase II (Pol II) in the nucleoplasm and then translated into proteins in the cytoplasm. The RPs are then imported into the nucleus and nucleolus for assembly into their respective ribosomal subunits. … RNA Polymerase II (Pol II) transcribes genes encoding the ~80 ribosomal proteins (RPs), over 200 RiBi assembly factors, and over 200 small nucleolar RNPs (snoRNPs) in the nucleoplasm [ 17 , 18 , 19 ]. …

Ribosome Biogenesis and Function in Cancer: From Mechanisms to Therapy.

Ribosome biogenesis is a highly coordinated, multi-step process that assembles the ribosomal machinery responsible for translating mRNAs into proteins. It begins with the rate-limiting step of RNA polymerase I (Pol I) transcription of the 47S ribosomal RNA (rRNA) genes within a specialised nucleolar region in the nucleus, followed by rRNA processing, modification, and assembly with ribosomal proteins and the 5S rRNA produced by Pol III. The ribosomal subunits are then exported to the cytoplasm to form functional ribosomes. This process is tightly regulated by the PI3K/RAS/MYC oncogenic network

Primed for global coronavirus pandemic: Emerging research and clinical outcome.

The global effort to combat and contain the coronavirus disease 2019 (COVID-19) caused by the recently discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now proceeding on a war footing. The world was slow to react to the developing crisis, but once the contours of the impending calamity became evident, the different state and non-state actors have raced to put their act together. The COVID-19 pandemic has blatantly exposed the shortcomings of our healthcare system and the limitations of medical science, despite considerable advances in recent years. To effectively tack

Recent advances in development of CDK7 inhibitors and their clinical trials: a narrative review.

Background and objectiveCDK7, a member of the CDK-activating kinase (CAK) family, plays a key role in cell cycle, transcriptional regulation and in regulating the proliferation and apoptosis of tumor cells. Some evidence suggests that CDK7 is a promising target for cancer treatments, so it is of great significance to develop an efficient and highly selective CDK7 inhibitor. CDK7 inhibitors have not yet been marketed. This review focuses on some selective CDK7 inhibitors currently in clinical research, and introduces their targets, indications, and the latest clinical trial progress in detail.M

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… During RNA polymerase II-mediated transcription: (I) In initiation, TFIIH helicases unwind promoter DNA while CDK7 phosphorylates Ser5/7 residues of the RNA polymerase II c-terminal domain (CTD), facilitating promoter clearance ( 18 - 20 ). … polymerase II. …

Drug repurposing approach to fight COVID-19.

Currently, there are no treatment options available for the deadly contagious disease, coronavirus disease 2019 (COVID-19). Drug repurposing is a process of identifying new uses for approved or investigational drugs and it is considered as a very effective strategy for drug discovery as it involves less time and cost to find a therapeutic agent in comparison to the de novo drug discovery process. The present review will focus on the repurposing efficacy of the currently used drugs against COVID-19 and their mechanisms of action, pharmacokinetics, dosing, safety, and their future perspective. R

Perturbing Enhancer Activity in Cancer Therapy.

Tight regulation of gene transcription is essential for normal development, tissue homeostasis, and disease-free survival. Enhancers are distal regulatory elements in the genome that provide specificity to gene expression programs and are frequently misregulated in cancer. Recent studies examined various enhancer-driven malignant dependencies and identified different approaches to specifically target these programs. In this review, we describe numerous features that make enhancers good transcriptional targets in cancer therapy and discuss different approaches to overcome enhancer perturbation.

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… Ready, pause, go: Regulation of RNA polymerase II pausing and release by cellular signaling pathways Trends Biochem. Sci. 2015 40 516 525 10.1016/j.tibs.2015.07.003 26254229 PMC4553066 117. Washburn R.S. Gottesman M.E. … Cdk7 is required for full activation of Drosophila heat shock genes and RNA polymerase II phosphorylation in vivo Mol. Cell. Biol. 2003 23 6876 6886 10.1128/MCB.23.19.6876-6886.2003 12972606 PMC193928 125. Lolli G. …

Chromatin structure, transcriptional activity and DNA repair efficiency affect the outcome of chemotherapy in multiple myeloma.

BackgroundMelphalan is one of the most active chemotherapeutic agents in the treatment of multiple myeloma (MM). However, the mechanism underlying differential patient responses to melphalan therapy is unknown.MethodsChromatin structure, transcriptional activity and DNA damage response signals were examined following ex vivo treatment with melphalan of both malignant bone marrow plasma cells (BMPCs) and peripheral blood mononuclear cells (PBMCs) of MM patients, responders (n=57) or non-responders (n=28) to melphalan therapy. PBMCs from healthy controls (n=25) were also included in the study.Re

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… That is, BMPCs from non-responders repair melphalan-induced N -alkylpurines located in the TS very rapidly resulting in fewer remaining DNA lesions, low number of blocked RNA polymerase II molecules and thus lower severity and faster recovery of transcription inhibition. … Reduced repair efficiency of the TS of active genes correlates with high numbers of blocked RNA polymerase II complexes acting as lesion detectors, phosphorylation of p53 at serine 15, increased cellular chemosensitivity and better clinical response to melphalan therapy. …