52,684 results match your criteria initiation factor

Zebrafish Minichromosome Maintenance Protein 5 Gene Regulates the Development and Migration of Facial Motor Neurons via Fibroblast Growth Factor Signaling.

Dev Neurosci 2021 Jun 15:1-11. Epub 2021 Jun 15.

Department of Histology and Embryology, Department of Pathology, Development and Regeneration Key Lab of Sichuan Province, Chengdu Medical College, Chengdu, China.

Minichromosome maintenance protein 5 (MCM5), a member of the microchromosomal maintenance protein family, plays an important role in the initiation and extension of DNA replication. However, its role in neural development in zebrafish remains unclear. Here, we used morpholino (MO) and CRISPR/Cas9 to knock down mcm5 and investigated the developmental features of facial motor neurons (FMNs) in the hindbrain of zebrafish. Read More

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Inhibition of translation initiation factor eIF4a inactivates heat shock factor 1 (HSF1) and exerts anti-leukemia activity in AML.

Leukemia 2021 Jun 14. Epub 2021 Jun 14.

Department of Leukemia, Section of Molecular Hematology and Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Eukaryotic initiation factor 4A (eIF4A), the enzymatic core of the eIF4F complex essential for translation initiation, plays a key role in the oncogenic reprogramming of protein synthesis, and thus is a putative therapeutic target in cancer. As important component of its anticancer activity, inhibition of translation initiation can alleviate oncogenic activation of HSF1, a stress-inducible transcription factor that enables cancer cell growth and survival. Here, we show that primary acute myeloid leukemia (AML) cells exhibit the highest transcript levels of eIF4A1 compared to other cancer types. Read More

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Distinct mechanisms of the human mitoribosome recycling and antibiotic resistance.

Nat Commun 2021 06 14;12(1):3607. Epub 2021 Jun 14.

Division of Translational Medicine, Wadsworth Center, New York State Department of Health, Empire State Plaza, Albany, NY, USA.

Ribosomes are recycled for a new round of translation initiation by dissociation of ribosomal subunits, messenger RNA and transfer RNA from their translational post-termination complex. Here we present cryo-EM structures of the human 55S mitochondrial ribosome (mitoribosome) and the mitoribosomal large 39S subunit in complex with mitoribosome recycling factor (RRF) and a recycling-specific homolog of elongation factor G (EF-G2). These structures clarify an unusual role of a mitochondria-specific segment of RRF, identify the structural distinctions that confer functional specificity to EF-G2, and show that the deacylated tRNA remains with the dissociated 39S subunit, suggesting a distinct sequence of events in mitoribosome recycling. Read More

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Intravitreal anti-VEGF use in France: a cross-sectional and longitudinal Nationwide observational study.

Acta Ophthalmol 2021 Jun 14. Epub 2021 Jun 14.

EPI-PHARE (French National Agency for Medicines and Health Products Safety (ANSM) and French National Health Insurance (CNAM)), Saint-Denis, France.

Purpose: To describe the sociodemographic, medical and management characteristics of patients using intravitreal (IVT) anti-vascular endothelial growth factors (VEGF) in France.

Methods: An observational study was conducted in patients treated with IVT ranibizumab or aflibercept, aged 18 years or older using the French National Health Insurance Databases covering 99% of the French population. Patients currently treated in 2018 were included in a cross-sectional approach to describe treatment history over the previous 6 years. Read More

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Long non-coding RNA NORAD inhibition upregulates microRNA-323a-3p to suppress tumorigenesis and development of breast cancer through the PUM1/eIF2 axis.

Cell Cycle 2021 Jun 14:1-13. Epub 2021 Jun 14.

Department of Thyroid and Breast Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Long non-coding RNAs (lncRNAs) are known to competitively bind with microRNAs (miRNAs) to participate in human cancers. We aim to explore the role of non-coding RNA activated by DNA damage (NORAD) binding to miR-323a-3p in breast cancer (BC) with the involvement of pumilio RNA-binding family member 1 (PUM1)/eukaryotic initiation factor 2 (eIF2) axis. Expression of NORAD, miR-323a-3p and PUM1 in tissues and cell lines was detected, and the correlation between NORAD expression and clinicopathological features of BC patients was analyzed. Read More

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Prevalence and risk factors of hemodynamic instability associated with preload-dependence during continuous renal replacement therapy in a prospective observational cohort of critically ill patients.

Ann Intensive Care 2021 Jun 14;11(1):95. Epub 2021 Jun 14.

Service de Médecine Intensive - Réanimation, Hôpital De La Croix Rousse, Hospices Civils de Lyon, 103 Grande Rue de la Croix Rousse, 69004, Lyon, France.

Background: Hemodynamic instability is a frequent complication of continuous renal replacement therapy (CRRT). Postural tests (i.e. Read More

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Efficacy and safety of modified fluorouracil/leucovorin plus irinotecan and oxaliplatin (mFOLFIRINOX) compared with S-1 as second-line chemotherapy in metastatic pancreatic cancer.

JGH Open 2021 Jun 10;5(6):679-685. Epub 2021 May 10.

Department of Hepatobiliary and Pancreatic Oncology Osaka International Cancer Institute Osaka Japan.

Background And Aim: The optimal standard second-line chemotherapy for metastatic pancreatic cancer (MPC) remains unclear. Here, we evaluated the efficacy and safety of modified fluorouracil/leucovorin plus irinotecan and oxaliplatin (mFOLFIRINOX) compared with oral fluoropyrimidine S-1 as a second-line chemotherapy in patients with MPC.

Methods: We retrospectively reviewed 76 consecutive patients with metastatic pancreatic adenocarcinoma who underwent mFOLFIRINOX or S-1 treatment as a second-line chemotherapy after gemcitabine plus nab-paclitaxel (GnP) failure at our department between December 2014 and February 2019. Read More

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A Robust Mammary Organoid System to Model Lactation and Involution-like Processes.

Bio Protoc 2021 Apr 20;11(8):e3996. Epub 2021 Apr 20.

Cellular Plasticity & Disease Modeling - Department of Developmental & Stem Cell Biology, CNRS UMR3738 - Institut Pasteur, 25 rue du Dr Roux, Paris 75015, France.

The mammary gland is a highly dynamic tissue that changes throughout reproductive life, including growth during puberty and repetitive cycles of pregnancy and involution. Mammary gland tumors represent the most common cancer diagnosed in women worldwide. Studying the regulatory mechanisms of mammary gland development is essential for understanding how dysregulation can lead to breast cancer initiation and progression. Read More

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Identification of Two Novel Compound Heterozygous Mutations Underlying Wolcott-Rallison Syndrome in a Chinese Family.

Front Pediatr 2021 26;9:679646. Epub 2021 May 26.

Institutes of Biomedical Sciences, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan, China.

Wolcott-Rallison syndrome is a rare autosomal recessive inheritance disorder caused by the defectiveness of eukaryotic translation initiation factor 2 alpha kinase 3 (), which encodes the PKR-like endoplasmic reticulum kinase (PERK). Defect in results in a permanent diabetes in early infancy or newborn period, a tendency to develop skeletal fractures and other associated disorders such as severe liver and renal dysfunction, and central hypothyroidism. Two patients with Wolcott-Rallison syndrome-like manifestations in a Chinese family and family members were genetically analyzed to identify if any variations that occurred in , which may cause Wolcott-Rallison syndrome. Read More

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Cryptococcal Meningitis in an HIV-Negative Puerperal Woman.

Case Rep Infect Dis 2021 25;2021:6665624. Epub 2021 May 25.

Head of Department of Infectious Diseases, Infectious Diseases Service, Hospital Garcia de Orta EPE, Almada, Portugal.

Cryptococcal meningitis is a common opportunistic infection in HIV-infected patients and other immunocompromised people. Pregnancy, which is a state of relative immunosuppression, can also be a risk factor for the development of cryptococcal meningitis. We report a clinical case of a 41-year-old woman who developed a severe meningeal syndrome after an otherwise normal pregnancy. Read More

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Decreased microRNA-768-3p expression indicates a poor prognosis in patients with breast cancer and promotes breast cancer cell viability, migration and invasion.

Oncol Lett 2021 Aug 2;22(2):579. Epub 2021 Jun 2.

Department of Oncology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261031, P.R. China.

Breast cancer is the most common malignancy in women and microRNA-768-3p (miR-768-3p) is abnormally expressed in hepatocellular carcinoma, non-small cell lung carcinomas and melanoma. The aim of the present study was to evaluate the prognostic value and biological function of miR-768-3p in breast cancer. The expression of miR-768-3p in tumor tissues and adjacent tissues of 116 patients with breast cancer obtained by surgery and normal breast cell lines MCF-10A and breast cancer cell lines (MCF-7, MDA-MB-231, T-47D and SK-BR-3) were detected by reverse transcription-quantitative PCR. Read More

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The Interaction Between Microglia and Macroglia in Glaucoma.

Front Neurosci 2021 28;15:610788. Epub 2021 May 28.

Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai General Hospital, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China.

Glaucoma, a neurodegenerative disease that leads to irreversible vision loss, is characterized by progressive loss of retinal ganglion cells (RGCs) and optic axons. To date, elevated intraocular pressure (IOP) has been recognized as the main phenotypic factor associated with glaucoma. However, some patients with normal IOP also have glaucomatous visual impairment and RGC loss. Read More

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Liver stiffness assessed by shear-wave elastography declines in parallel with immunoregulatory proteins in patients with chronic HCV infection during DAA therapy.

Clin Hemorheol Microcirc 2021 Jun 8. Epub 2021 Jun 8.

Department of Gastroenterology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, Regensburg, Germany.

Background: A rapid decline of liver stiffness (LS) was detected by non-invasive methods in patients with chronic hepatitis C (HCV) infection during treatment with direct-acting antivirals (DAA).

Objective: To investigate the influence of inflammation on LS.

Methods: We prospectively examined LS by sonographic shear-wave elastography in 217 patients during DAA therapy from treatment initiation (BL) to 12 weeks after end of therapy (SVR12). Read More

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[Pyoderma gangrenosum].

Ugeskr Laeger 2021 Jun;183(24)

Pyoderma gangrenosum is a diagnostic and therapeutic challenge. A misdiagnosis or delayed diagnosis can lead to increased morbidity and death. A fast workup and initiation of treatment is essential. Read More

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Mechanisms of triggering malaria gametocytogenesis by AP2-G.

Parasitol Int 2021 Jun 10:102403. Epub 2021 Jun 10.

Department of Medical Zoology, Mie University School of Medicine, Mie, Tsu 514-8507, Japan.

The transcription factor (TF) AP2-G is essential for gametocytogenesis in the malaria parasite; however, it remains unclear if AP2-G determines commitment to sexual stage development fate in the schizont stage, or whether AP2-G directly initiates sexual stage differentiation and development beginning in the late-trophozoite stage. In this study, we addressed this issue by investigating the expression profile of AP2-G and determining genome-wide target genes in Plasmodium berghei. Fluorescence microscopy showed that AP2-G expression was first observed in the parasite 12 h after erythrocyte invasion and peaked at 18 h when sexual features were first manifested in early gametocytes. Read More

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Predictive value of change in effective arterial elastance in norepinephrine weaning: a retrospective study.

Ann Palliat Med 2021 Jun 7. Epub 2021 Jun 7.

Medical Intensive Care Unit, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Background: The weaning of vasopressors is usually an empirical choice made by clinicians. The aim of this study is to assess the predictive value of change in effective arterial elastance (ΔEa%) induced by fluid administration in early initiation of norepinephrine (NE) weaning.

Methods: Included were intensive care unit (ICU) septic shock patients with an indwelling pulmonary artery catheter who experienced initial resuscitation and required a fluid challenge. Read More

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Trastuzumab-induced cardiotoxicity: a review of clinical risk factors, pharmacologic prevention, and cardiotoxicity of other HER2-directed therapies.

Breast Cancer Res Treat 2021 Jun 11. Epub 2021 Jun 11.

Georgetown Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Rd NW, Washington, DC, 20007, USA.

Purpose: Despite great success as a targeted breast cancer therapy, trastuzumab use may be complicated by heart failure and loss of left ventricular contractile function. This review summarizes the risk factors, imaging, and prevention of cardiotoxicity associated with trastuzumab and other HER2-targeted therapies.

Findings: Cardiovascular disease risk factors, advanced age, and previous anthracycline treatment predispose to trastuzumab-induced cardiotoxicity (TIC), with anthracycline exposure being the most significant risk factor. Read More

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Contactless Sleep Monitoring for Early Detection of Health Deteriorations in Community-Dwelling Older Adults: Exploratory Study.

JMIR Mhealth Uhealth 2021 Jun 11;9(6):e24666. Epub 2021 Jun 11.

Gerontechnology and Rehabilitation Group, ARTORG Center for Biomedical Engineering Research, University of Bern, Bern, Switzerland.

Background: Population aging is posing multiple social and economic challenges to society. One such challenge is the social and economic burden related to increased health care expenditure caused by early institutionalizations. The use of modern pervasive computing technology makes it possible to continuously monitor the health status of community-dwelling older adults at home. Read More

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Atrial remodeling and atrial fibrillation in acquired forms of cardiovascular disease.

Heart Rhythm O2 2020 Jun 18;1(2):147-159. Epub 2020 May 18.

Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

Atrial fibrillation (AF) is prevalent in common conditions and acquired forms of heart disease, including diabetes mellitus (DM), hypertension, cardiac hypertrophy, and heart failure. AF is also prevalent in aging. Although acquired heart disease is common in aging individuals, age is also an independent risk factor for AF. Read More

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Tocilizumab decreases T cells but not macrophages in the synovium of patients with rheumatoid arthritis while it increases the levels of serum interleukin-6 and RANKL.

RMD Open 2021 Jun;7(2)

Rheumatology Unit, Department of Gastroentorogy, Dematology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden.

Objectives: Our knowledge about the effect of tocilizumab (TCZ) on the synovium in rheumatoid arthritis (RA) is limited. The aim of this study was to investigate the effect of TCZ on citrullination and on inflammation in the synovial tissue and in the peripheral blood.

Methods: 15 patients with RA underwent synovial biopsy before and 8 weeks after TCZ initiation. Read More

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Protective effects of sodium butyrate on rotavirus inducing endoplasmic reticulum stress-mediated apoptosis via PERK-eIF2α signaling pathway in IPEC-J2 cells.

J Anim Sci Biotechnol 2021 Jun 11;12(1):69. Epub 2021 Jun 11.

Institute of Animal Nutrition, Sichuan Agricultural University, Huimin Road 211#, Chengdu, Sichuan Province, 611130, P. R. China.

Background: Rotavirus (RV) is a major pathogen that causes severe gastroenteritis in infants and young animals. Endoplasmic reticulum (ER) stress and subsequent apoptosis play pivotal role in virus infection. However, the protective mechanisms of intestinal damage caused by RV are poorly defined, especially the molecular pathways related to enterocytes apoptosis. Read More

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FOXR2 Stabilizes MYCN Protein and Identifies Non--Amplified Neuroblastoma Patients With Unfavorable Outcome.

J Clin Oncol 2021 Jun 10:JCO2002540. Epub 2021 Jun 10.

Hopp-Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.

Purpose: Clinical outcomes of patients with neuroblastoma range from spontaneous tumor regression to fatality. Hence, understanding the mechanisms that cause tumor progression is crucial for the treatment of patients. In this study, we show that activation identifies a subset of neuroblastoma tumors with unfavorable outcome and we investigate the mechanism how FOXR2 relates to poor outcome in patients. Read More

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Serum and hematologic responses after three cycles of cabazitaxel therapy as predictors of survival in castration-resistant prostate cancer.

Cancer Chemother Pharmacol 2021 Jun 10. Epub 2021 Jun 10.

Department of Urology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.

Background: In this study, we investigated the association between the early response of serum and hematological variables and the outcome of cabazitaxel therapy.

Patients And Methods: The medical records of 59 consecutive patients who had previously received docetaxel chemotherapy for the treatment of metastatic castration-resistant prostate cancer (CRPC) and who received cabazitaxel at our hospital between January 2011 and March 2020 were retrospectively reviewed and statistically analyzed.

Results: The median follow-up period after cabazitaxel initiation was 15. Read More

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Identifying Dendritic Cell-Related Genes Through a Co-Expression Network to Construct a 12-Gene Risk-Scoring Model for Predicting Hepatocellular Carcinoma Prognosis.

Front Mol Biosci 2021 24;8:636991. Epub 2021 May 24.

Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

The prognostic prediction of hepatocellular carcinoma (HCC) is still challenging. Immune cells play a crucial role in tumor initiation, progression, and drug resistance. However, prognostic value of immune-related genes in HCC remains to be further clarified. Read More

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Site-specific resolution of enthesitis in patients with axial spondyloarthritis treated with tumor necrosis factor inhibitors.

Arthritis Res Ther 2021 Jun 9;23(1):165. Epub 2021 Jun 9.

Department of Rheumatology, Lausanne University Hospital (CHUV), Lausanne, Switzerland.

Background: Enthesitis is a hallmark of spondyloarthritis (SpA) with a substantial impact on quality of life. Reports of treatment effectiveness across individual enthesitis sites in real-world patients with axial SpA (axSpA) are limited. We investigated the evolution of enthesitis following tumor necrosis factor inhibitor (TNFi) initiation in axSpA patients, both cumulatively and at specific axial and peripheral sites. Read More

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Adjunct Immune Globulin for Vaccine-Induced Thrombotic Thrombocytopenia.

N Engl J Med 2021 Jun 9. Epub 2021 Jun 9.

From the Departments of Medicine (A.B., D.M.A., T.E.W., J.W.S., Z.A.A.A.M., A.S., J.G.K., I.N.) and Pathology and Molecular Medicine (A.B., T.E.W.), Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, the Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB (T.P., J.M.S.), the Department of Hematology/Oncology, Centre Hospitalier de l'Université de Montreal, Montreal (N.B.), and the Department of Hematology/Oncology, Hôpital Régional de Saint-Jérôme, St. Jerome, QC (M.-C.L.) - all in Canada.

The use of high-dose intravenous immune globulin (IVIG) plus anticoagulation is recommended for the treatment of vaccine-induced immune thrombotic thrombocytopenia (VITT), a rare side effect of adenoviral vector vaccines against coronavirus disease 2019 (Covid-19). We describe the response to IVIG therapy in three of the first patients in whom VITT was identified in Canada after the receipt of the ChAdOx1 nCoV-19 vaccine. The patients were between the ages of 63 and 72 years; one was female. Read More

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Zika Virus Induces an Atypical Tripartite Unfolded Protein Response with Sustained Sensor and Transient Effector Activation and a Blunted BiP Response.

mSphere 2021 Jun 9:e0036121. Epub 2021 Jun 9.

Faculty of Biology, Medicine and Health, School of Biological Sciences, The University of Manchester, Manchester, United Kingdom.

To study how the Zika virus (ZIKV) interacts with the host unfolded protein response (UPR), we undertook a kinetics study. We show that ZIKV infection triggers an atypical tripartite UPR in A549 cells involving transient activation of the effectors X-box-binding protein 1, activating transcription factor 4 (ATF4), CCAAT enhancer-binding protein-homologous protein, and growth arrest and DNA damage-inducible protein 34 during early infection and sustained activation of all three UPR sensors: RNA-activated protein kinase-like endoplasmic reticulum-resident kinase (PERK), inositol-requiring kinase-1α (IRE1α), and ATF6. Sustained phosphorylation of the eukaryotic translation initiation factor 2α and rRNA degradation coincide with host translational shutoff, cell lysis, and virus release during late infection. Read More

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Hematological parameters abnormalities and associated factors in HIV-positive adults before and after highly active antiretroviral treatment in Goba Referral Hospital, southeast Ethiopia: A cross-sectional study.

SAGE Open Med 2021 28;9:20503121211020175. Epub 2021 May 28.

School of Medical Laboratory Sciences, Institute of Health, Jimma University, Jimma, Ethiopia.

Objectives: Hematological abnormalities of the major blood cell lines are frequently reported in patients with HIV-1 infection, in patients without antiretroviral therapy, and during the advanced stages of the disease. Chronic immune activation and inflammation results in the progressive depletion of CD4+ T-cells play a significant role in the clinical progression and pathogenesis of this infection. This study was aimed at assessing the prevalence of hematological abnormalities and their associated factors before and after the initiation of antiretroviral therapy in adults with HIV-1 infection in a referral hospital. Read More

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Comparative phytochemistry of flavaglines (= rocaglamides), a group of highly bioactive flavolignans from species (Meliaceae).

Harald Greger

Phytochem Rev 2021 Jun 4:1-40. Epub 2021 Jun 4.

Chemodiversity Research Group, Faculty of Life Sciences, University of Vienna, Rennweg 14, 1030 Wien, Austria.

Flavaglines are formed by cycloaddition of a flavonoid nucleus with a cinnamic acid moiety representing a typical chemical character of the genus of the family Meliaceae. Based on biosynthetic considerations 148 derivatives are grouped together into three skeletal types representing 77 cyclopenta[]benzofurans, 61 cyclopenta[]benzopyrans, and 10 benzo[]oxepines. Apart from different hydroxy, methoxy, and methylenedioxy groups of the aromatic rings, important structural variation is created by different substitutions and stereochemistries of the central cyclopentane ring. Read More

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Transglutaminase 2 promotes tumorigenicity of colon cancer cells by inactivation of the tumor suppressor p53.

Oncogene 2021 Jun 8. Epub 2021 Jun 8.

Goethe University Hospital Frankfurt, Department of Medicine, Hematology/Oncology, Frankfurt am Main, Germany.

Despite a high clinical need for the treatment of colorectal carcinoma (CRC) as the second leading cause of cancer-related deaths, targeted therapies are still limited. The multifunctional enzyme Transglutaminase 2 (TGM2), which harbors transamidation and GTPase activity, has been implicated in the development and progression of different types of human cancers. However, the mechanism and role of TGM2 in colorectal cancer are poorly understood. Read More

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