DSIF factor Spt5 coordinates transcription, maturation and exoribonucleolysis of RNA polymerase II transcripts.

Precursor messenger RNA (pre-mRNA) is processed into its functional form during RNA polymerase II (Pol II) transcription. Although functional coupling between transcription and pre-mRNA processing is established, the underlying mechanisms are not fully understood. We show that the key transcription termination factor, RNA exonuclease Xrn2 engages with Pol II forming a stable complex.

First record of the genus Haritalodes Warren, 1890 and H. derogata (Fabricius, 1775) (Lepidoptera: Crambidae: Spilomelinae) from Türkiye and its morphological and molecular identification.

The genus Haritalodes Warren, 1890 is represented by 12 species worldwide except in the Nearctic and Neotropical regions. Haritalodes derogata (Fabricius, 1775), commonly known as the cotton leaf roller moth, is the most widely distributed species of the genus and is common in the West Palaearctic Region. This species is one of the most serious pests of Malvaceae.

DEAD-box ATPase Dbp2 is the key enzyme in an mRNP assembly checkpoint at the 3'-end of genes and involved in the recycling of cleavage factors.

mRNA biogenesis in the eukaryotic nucleus is a highly complex process. The numerous RNA processing steps are tightly coordinated to ensure that only fully processed transcripts are released from chromatin for export from the nucleus. Here, we present the hypothesis that fission yeast Dbp2, a ribonucleoprotein complex (RNP) remodelling ATPase of the DEAD-box family, is the key enzyme in an RNP assembly checkpoint at the 3'-end of genes.

Impact of Surgery-Induced Myeloid-derived Suppressor Cells and the NOX2/ROS Axis on Postoperative Survival in Human Pancreatic Cancer.

Unlabelled: Preclinical studies imply that surgery triggers inflammation that may entail tumor outgrowth and metastasis. The potential impact of surgery-induced inflammation in human pancreatic cancer is insufficiently explored. This study included 17 patients with periampullary cancer [pancreatic ductal adenocarcinoma (PDAC) n = 14, ampullary carcinoma n = 2, cholangiocarcinoma n = 1] undergoing major pancreatic cancer surgery with curative intent.

Preserving nutrient content in red cabbage juice powder via foam-mat hybrid microwave drying: Application in fortified functional pancakes.

Red cabbage, a highly nutritious cool-season cruciferous vegetable, is rich in anthocyanins; however, the instability of anthocyanins during processing and storage poses challenges. This study aimed to optimize the foam-mat drying process of red cabbage juice (RCJ) with a high anthocyanin content using a hybrid microwave hot air-drying system (MW-HAD) as a dehydration method compared to conventional techniques (HAD) using response surface methodology (RSM). Additionally, the produced red cabbage juice powder (RCJP) was used to enrich the pancake formulation.

Comparison of ohmic heating- and microwave-assisted extraction techniques for avocado leaves valorization: Optimization and impact on the phenolic compounds and bioactivities.

Avocado tree pruning activities generate a substantial amount of residual biomass, which includes different parts of the plant, such as leaves, twigs, branches, and small fruits. This study aimed to investigate the impact of different green extraction methods of microwave-assisted extraction (MAE) and ohmic heating-assisted extraction (OHAE) for the phenolic extraction of avocado leaves based on a statistical approach, central composite design (CCD), and response surface methodology (RSM). Water was preferred using as an environmentally and health-friendly solvent for both methods.

A New Approach for the Development and Optimization of Gluten-Free Noodles Using Flours from Byproducts of Cold-Pressed Okra and Pumpkin Seeds.

The significant protein and dietary fiber content of cold-pressed pumpkin (PSF) and okra (OSF) seed byproducts are well-known. However, their impact on noodles' nutritional quality has never been studied. For the first time, noodle formulation was developed employing a genetic algorithm in the R programming language to achieve the most optimal sensory attributes as well as nutritional composition, color, cooking, and textural properties.

Kluai Hin (Musa sapientum Linn.) peel as a source of functional polyphenols identified by HPLC-ESI-QTOF-MS and its potential antidiabetic function.

To date, information on the polyphenolic composition of Kluai Hin banana peel and pulp and the potential antidiabetic activity of its major active compounds is limited. This study aimed to identify polyphenols in extracts of fresh and freeze-dried Kluai Hin banana peel and pulp (methanol:water; M:W, 80:20 for flavonoids and acetone:water:acetic acid; A:W:A, 50:49:1 for phenolic acids) by RP-HPLC-DAD and HPLC-ESI-QTOF-MS. Additionally, inhibition of α-amylase and α-glucosidase activities was investigated with crude extracts from Kluai Hin banana peel and pulp, and compared with its major polyphenols ((+)-catechin, (-)-epicatechin and gallic acid) and the antidiabetic drug acarbose.

Acute Effect of Riceberry Waffle Intake on Postprandial Glycemic Response in Healthy Subjects.

Gluten-free products have been developed due to increasing consumer demand. The improvement of the sensory quality and nutritional value of these products may support functional food development and provide health benefits. The purpose of this study was to develop a gluten-free waffle formulation with Riceberry rice flour by replacing the sucrose with maltitol and palm sugar powder.

Impact of IL-1β and the IL-1R antagonist on relapse risk and survival in AML patients undergoing immunotherapy for remission maintenance.

Interleukin-1 beta (IL-1β), a pro-inflammatory cytokine, has been ascribed a role in the expansion of myeloid progenitors in acute myeloid leukemia (AML) and in promoting myeloid cell-induced suppression of lymphocyte-mediated immunity against malignant cells. This study aimed at defining the potential impact of IL-1β in the post-remission phase of AML patients receiving immunotherapy for relapse prevention in an international phase IV trial of 84 patients (ClinicalTrials.gov; NCT01347996).

Phosphoinositide 3-Kinase Signaling in the Tumor Microenvironment: What Do We Need to Consider When Treating Chronic Lymphocytic Leukemia With PI3K Inhibitors?

Phosphoinositide 3-kinases (PI3Ks) and their downstream proteins constitute a signaling pathway that is involved in both normal cell growth and malignant transformation of cells. Under physiological conditions, PI3K signaling regulates various cellular functions such as apoptosis, survival, proliferation, and growth, depending on the extracellular signals. A deterioration of these extracellular signals caused by mutational damage in oncogenes or growth factor receptors may result in hyperactivation of this signaling cascade, which is recognized as a hallmark of cancer.

NOX2-Derived Reactive Oxygen Species in Cancer.

The formation of reactive oxygen species (ROS) by the myeloid cell NADPH oxidase NOX2 is critical for the destruction of engulfed microorganisms. However, recent studies imply that ROS, formed by NOX2 myeloid cells in the malignant microenvironment, exert multiple actions of relevance to the growth and spread of neoplastic cells. By generating ROS, tumor-infiltrating myeloid cells and NOX2 leukemic myeloid cells may thus (i) compromise the function and viability of adjacent cytotoxic lymphocytes, including natural killer (NK) cells and T cells, (ii) oxidize DNA to trigger cancer-promoting somatic mutations, and (iii) affect the redox balance in cancer cells to control their proliferation and survival.

Idelalisib Rescues Natural Killer Cells from Monocyte-Induced Immunosuppression by Inhibiting NOX2-Derived Reactive Oxygen Species.

The phosphatidylinositol-4,5-bisphosphate-3 kinase-δ (PI3Kδ) inhibitor idelalisib, used alone or in combination with anti-CD20, is clinically efficacious in B-cell lymphoma and chronic lymphocytic leukemia (CLL) by promoting apoptosis of malignant B cells. PI3K regulates the formation of reactive oxygen species (ROS) by the myeloid NADPH oxidase NOX2, but the role of PI3Kδ in myeloid cell-induced immunosuppression is unexplored. We assessed the effects of idelalisib on the spontaneous and IgG antibody-induced ROS production by human monocytes, on ROS-induced cell death of human natural killer (NK) cells, and on tumor cell clearance in an NK cell-dependent mouse model of metastasis.

System-wide analyses of the fission yeast poly(A) RNA interactome reveal insights into organization and function of RNA-protein complexes.

Large RNA-binding complexes play a central role in gene expression and orchestrate production, function, and turnover of mRNAs. The accuracy and dynamics of RNA-protein interactions within these molecular machines are essential for their function and are mediated by RNA-binding proteins (RBPs). Here, we show that fission yeast whole-cell poly(A) RNA-protein crosslinking data provide information on the organization of RNA-protein complexes.

Isolated limb perfusion with melphalan activates interferon-stimulated genes to induce tumor regression in patients with melanoma in-transit metastasis.

Hyperthermic isolated limb perfusion (ILP) with high-dose melphalan is a treatment option for melanoma patients with metastasis confined to limbs (in-transit metastasis). The therapy entails a complete response (CR) rate of 50-70%. Cellular immunity is proposed to impact on the clinical efficacy of ILP, but the detailed aspects of ILP-induced immune activation remain to be explored.

Increased risk of brain metastases in ovarian cancer patients with BRCA mutations.

Purpose: To estimate the risk for brain metastases in patients with ovarian cancer using real-world data, and assess whether BRCA mutations increase that risk.

Methods: This retrospective study included 4515 patients diagnosed with ovarian cancer between January 1, 2011, and January 31, 2018, from the Flatiron Health database, a longitudinal, demographically, and geographically diverse database derived from electronic health records in the United States.

Results: Forty-six (1%) patients were diagnosed with brain metastases after being diagnosed with ovarian cancer.

NOX2 inhibition reduces oxidative stress and prolongs survival in murine KRAS-induced myeloproliferative disease.

Mutations leading to constitutive RAS activation contribute in myeloid leukemogenesis. RAS mutations in myeloid cells are accompanied by excessive formation of reactive oxygen species (ROS), but the source of ROS and their role for the initiation and progression of leukemia have not been clearly defined. To determine the role of NOX2-derived ROS in RAS-driven leukemia, double transgenic LSL-Kras × Mx1-Cre mice expressing oncogenic KRAS in hematopoietic cells (M-Kras) were treated with N-methyl-histamine (NMH) that targeted the production of NOX2-derived ROS in leukemic cells by agonist activity at histamine H receptors.

NOX2 in autoimmunity, tumor growth and metastasis.

Myeloid cell NADPH oxidase isoform 2 (NOX2) generates reactive oxygen species (ROS) that participate in defense against microbial pathogens. Humans with compromised NOX2-mediated ROS formation develop chronic granulomatous disease characterized by recurrent bacterial and fungal infections. Additionally, impaired NOX2 function entails hyperactive lymphocytes and autoimmunity in humans and in murine models.

Cytomegalovirus Serostatus Affects Autoreactive NK Cells and Outcomes of IL2-Based Immunotherapy in Acute Myeloid Leukemia.

Human cytomegalovirus (CMV) infection is reported to promote NK cell differentiation and education. The CMV-induced generation of highly differentiated adaptive-like NK cells has been proposed to affect favorably on the maintenance of remission in patients with acute myeloid leukemia (AML) after allogeneic stem cell transplantation (allo-SCT). The impact of CMV infection and adaptive-like NK cells on relapse and survival of patients with AML not receiving allo-SCT remains unknown.

Anti-Leukemic Properties of Histamine in Monocytic Leukemia: The Role of NOX2.

In patients with acute myeloid leukemia (AML), treatment with histamine dihydrochloride (HDC) and low-dose IL-2 (HDC/IL-2) in the post-chemotherapy phase has been shown to reduce the incidence of leukemic relapse. The clinical benefit of HDC/IL-2 is pronounced in monocytic forms of AML, where the leukemic cells express histamine type 2 receptors (HR) and the NAPDH oxidase-2 (NOX2). HDC ligates to HRs to inhibit NOX2-derived formation of reactive oxygen species, but details regarding the anti-leukemic actions of HDC remain to be elucidated.

Green and Chamomile Teas, but not Acarbose, Attenuate Glucose and Fructose Transport via Inhibition of GLUT2 and GLUT5.

Scope: High glycaemic sugars result in blood-glucose spikes, while large doses of post-prandial fructose inundate the liver, causing an imbalance in energy metabolism, both leading to increased risk of metabolic malfunction and type 2 diabetes. Acarbose, used for diabetes management, reduces post-prandial hyperglycaemia by delaying carbohydrate digestion.

Methods And Results: Chamomile and green teas both inhibited digestive enzymes (α-amylase and maltase) related to intestinal sugar release, as already established for acarbose.

Role of NOX2-Derived Reactive Oxygen Species in NK Cell-Mediated Control of Murine Melanoma Metastasis.

The NADPH oxidase of myeloid cells, NOX2, generates reactive oxygen species (ROS) to eliminate pathogens and malignant cells. NOX2-derived ROS have also been proposed to dampen functions of natural killer (NK) cells and other antineoplastic lymphocytes in the microenvironment of established tumors. The mechanisms by which NOX2 and ROS influence the process of distant metastasis have only been partially explored.

Sirtuin1 (SIRT1) in the Acetylation of Downstream Target Proteins.

Acetylation has been shown to be an important posttranslational modification (PTM) of both histone and nonhistone proteins with particular implications in cell signaling and transcriptional regulation of gene expression. Many studies have already demonstrated that SIRT1 is able to deacetylate histones and lead to gene silencing. It can also regulate the function of tumor suppressors including FOXO proteins and p53 by deacetylation.