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  • 1
    Language: English
    In: Science (American Association for the Advancement of Science), 2015-07-17, Vol.349 (6245), p.309-312
    Description: Morphinan alkaloids from the opium poppy are used for pain relief. The direction of metabolites to morphinan biosynthesis requires isomerization of (S)- to (R)-reticuline. Characterization of high-reticuline poppy mutants revealed a genetic locus, designated STORR [(S)- to (R)-reticuline] that encodes both cytochrome P450 and oxidoreductase modules, the latter belonging to the aldo-keto reductase family. Metabolite analysis of mutant alleles and heterologous expression demonstrate that the P450 module is responsible for the conversion of (S)-reticuline to 1,2-dehydroreticuline, whereas the oxidoreductase module converts 1,2-dehydroreticuline to (R)-reticuline rather than functioning as a P450 redox partner. Proteomic analysis confirmed that these two modules are contained on a single polypeptide in vivo. This modular assembly implies a selection pressure favoring substrate channeling. The fusion protein STORR may enable microbial-based morphinan production.
    Subject(s): REPORTS
    ISSN: 0036-8075
    E-ISSN: 1095-9203
    Source: JSTOR Life Sciences
    Source: Single Journals
    Source: Academic Search Ultimate
    Source: Alma/SFX Local Collection
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  • 2
    Language: English
    In: Science (American Association for the Advancement of Science), 2015-07-17, Vol.349 (6245), p.309-312
    Description: Morphinan alkaloids from the opium poppy are used for pain relief. The direction of metabolites to morphinan biosynthesis requires isomerization of (S)- to (R)-reticuline. Characterization of high-reticuline poppy mutants revealed a genetic locus, designated STORR [(S)- to (R)-reticuline] that encodes both cytochrome P450 and oxidoreductase modules, the latter belonging to the aldo-keto reductase family. Metabolite analysis of mutant alleles and heterologous expression demonstrate that the P450 module is responsible for the conversion of (S)-reticuline to 1,2-dehydroreticuline, whereas the oxidoreductase module converts 1,2-dehydroreticuline to (R)-reticuline rather than functioning as a P450 redox partner. Proteomic analysis confirmed that these two modules are contained on a single polypeptide in vivo. This modular assembly implies a selection pressure favoring substrate channeling. The fusion protein STORR may enable microbial-based morphinan production.
    Subject(s): Base Sequence ; Benzylisoquinolines - chemistry ; Benzylisoquinolines - metabolism ; Cytochrome P-450 Enzyme System - genetics ; Cytochrome P-450 Enzyme System - metabolism ; Genetic Loci ; Isoquinolines - chemistry ; Isoquinolines - metabolism ; Molecular Sequence Data ; Morphinans - chemistry ; Morphinans - metabolism ; Mutation ; Oxidation-Reduction ; Papaver - enzymology ; Papaver - genetics ; Plant Proteins - genetics ; Plant Proteins - metabolism ; Quaternary Ammonium Compounds - chemistry ; Quaternary Ammonium Compounds - metabolism
    E-ISSN: 1095-9203
    Source: JSTOR Life Sciences
    Source: Single Journals
    Source: Academic Search Ultimate
    Source: Alma/SFX Local Collection
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  • 3
    Language: English
    In: Science (American Association for the Advancement of Science), 2018-10-19, Vol.362 (6412), p.343-347
    Description: Morphinan-based painkillers are derived from opium poppy ( L.). We report a draft of the opium poppy genome, with 2.72 gigabases assembled into 11 chromosomes with contig N50 and scaffold N50 of 1.77 and 204 megabases, respectively. Synteny analysis suggests a whole-genome duplication at ~7.8 million years ago and ancient segmental or whole-genome duplication(s) that occurred before the Papaveraceae-Ranunculaceae divergence 110 million years ago. Syntenic blocks representative of phthalideisoquinoline and morphinan components of a benzylisoquinoline alkaloid cluster of 15 genes provide insight into how this cluster evolved. Paralog analysis identified P450 and oxidoreductase genes that combined to form the gene fusion essential for morphinan biosynthesis in opium poppy. Thus, gene duplication, rearrangement, and fusion events have led to evolution of specialized metabolic products in opium poppy.
    Subject(s): Alkaloids ; Analysis ; Benzylisoquinolines - metabolism ; Chemical properties ; Evolution, Molecular ; Gene Duplication ; Gene Fusion ; Gene Order ; Genes ; Genetic aspects ; Genome, Plant ; Genomes ; Genomics ; Morphinans - metabolism ; Multigene Family ; NADPH-Ferrihemoprotein Reductase - genetics ; Opioids ; Opium ; Opium poppy ; Papaver - genetics ; Papaver - metabolism ; Plant Proteins - genetics ; Production processes ; Synteny
    ISSN: 0036-8075
    E-ISSN: 1095-9203
    Source: Single Journals
    Source: Academic Search Ultimate
    Source: Alma/SFX Local Collection
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  • 4
    Language: English
    In: Science (American Association for the Advancement of Science), 2012-06-29, Vol.336 (6089), p.1704-1708
    Description: Noscapine is an antitumor alkaloid from opium poppy that binds tubulin, arrests metaphase, and induces apoptosis in dividing human cells. Elucidation of the biosynthetic pathway will enable improvement in the commercial production of noscapine and related bioactive molecules. Transcriptomic analysis revealed the exclusive expression of 10 genes encoding five distinct enzyme classes in a high noscapine-producing poppy variety, HN1. Analysis of an F₂ mapping population indicated that these genes are tightly linked in HN1, and bacterial artificial chromosome sequencing confirmed that they exist as a complex gene cluster for plant alkaloids. Virus-induced gene silencing resulted in accumulation of pathway intermediates, allowing gene function to be linked to noscapine synthesis and a novel biosynthetic pathway to be proposed.
    Subject(s): Alkaloids ; Antineoplastic Agents, Phytogenic - biosynthesis ; Biological and medical sciences ; Biosynthesis ; Capsules ; Classical genetics, quantitative genetics, hybrids ; Enzymes ; Fundamental and applied biological sciences. Psychology ; Gene silencing ; Genes ; Genes, Plant ; Genetic aspects ; Genetics of eukaryotes. Biological and molecular evolution ; Genomes ; Latex ; Libraries ; Molecular Sequence Data ; Morphinans ; Multigene Family ; Noscapine - metabolism ; Open reading frames ; Papaver - enzymology ; Papaver - genetics ; Papaver - metabolism ; Physiological aspects ; Pteridophyta, spermatophyta ; REPORTS ; Research ; Vegetals
    ISSN: 0036-8075
    E-ISSN: 1095-9203
    Source: JSTOR Life Sciences
    Source: Single Journals
    Source: Academic Search Ultimate
    Source: Alma/SFX Local Collection
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  • 5
    Language: English
    In: Medicina (Kaunas, Lithuania), 2020-12-23, Vol.57 (1), p.6
    Description: The combination of immune checkpoint inhibitors and definitive radiotherapy is investigated for the multimodal treatment of cisplatin non-eligible locally advanced head and neck cancers (HNC). In the case of recurrent and metastatic HNC, immunotherapy has shown benefit over the EXTREME protocol, being already considered the standard treatment. One of the biggest challenges of multimodal treatment is to establish the optimal therapy sequence so that the synergistic effect is maximal. Thus, superior results were obtained for the administration of anti-CTLA4 immunotherapy followed by hypofractionated radiotherapy, but the anti-PD-L1 therapy demonstrates the maximum potential of radio-sensitization of the tumor in case of concurrent administration. The synergistic effect of radiotherapy-immunotherapy (RT-IT) has been demonstrated in clinical practice, with an overall response rate of about 18% for HNC. Given the demonstrated potential of radiotherapy to activate the immune system through already known mechanisms, it is necessary to identify biomarkers that direct the "nonresponders" of immunotherapy towards a synergistic RT-IT stimulation strategy. Stimulation of the immune system by irradiation can convert "nonresponder" to "responder". With the development of modern techniques, re-irradiation is becoming an increasingly common option for patients who have previously been treated with higher doses of radiation. In this context, radiotherapy in combination with immunotherapy, both in the advanced local stage and in recurrent/metastatic of HNC radiotherapy, could evolve from the "first level" of knowledge (i.e., ballistic precision, dose conformity and homogeneity) to "level two" of "biological dose painting" (in which the concept of tumor heterogeneity and radio-resistance supports the need for doses escalation based on biological criteria), and finally to the "third level" ofthe new concept of "immunological dose painting". The peculiarity of this concept is that the radiotherapy target volumes and tumoricidal dose can be completely reevaluated, taking into account the immune-modulatory effect of irradiation. In this case, the tumor target volume can include even the tumor microenvironment or a partial volume of the primary tumor or metastasis, not all the gross and microscopic disease. Tumoricidal biologically equivalent dose (BED) may be completely different from the currently estimated values, radiotherapy treating the tumor in this case indirectly by boosting the immune response. Thus, the clinical target volume (CTV) can be replaced with a new immunological-clinical target volume (ICTV) for patients who benefit from the RT-IT association (Image 1).
    Subject(s): ab-scopal ; Cisplatin ; head and neck cancers ; Head and Neck Neoplasms - radiotherapy ; Humans ; Immunotherapy ; Opinion ; radiotherapy ; Re-Irradiation ; Tumor Burden ; Tumor Microenvironment
    ISSN: 1648-9144
    ISSN: 1010-660X
    E-ISSN: 1648-9144
    Source: PubMed Central
    Source: Alma/SFX Local Collection
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
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  • 6
    Language: English
    In: Molecules (Basel, Switzerland), 2014-08-12, Vol.19 (8), p.12011-12030
    Description: Novel derivatives were prepared by reaction of aromatic amines with 2-(4-ethylphenoxymethyl)benzoyl isothiocyanate, affording the N-[2-(4-ethylphenoxymethyl) benzoyl]-Nꞌ-(substituted phenyl)thiourea. Structural elucidation of these compounds was performed by IR, NMR spectroscopy and elemental analysis. The new compounds were used in combination with Fe3O4 and polyvinylpyrrolidone (PVP) for the coating of medical surfaces. In our experiments, catheter pieces were coated by Matrix Assisted Pulsed Laser Evaporation (MAPLE) technique. The microbial adherence ability was investigated in 6 multi-well plates by using culture based methods. The obtained surfaces were also assessed for their cytotoxicity with respect to osteoblast cells, by using fluorescence microscopy and MTT assay. The prepared surfaces by advanced laser processing inhibited the adherence and biofilm development ability of Staphylococcus aureus and Pseudomonas aeruginosa tested strains while cytotoxic effects on the 3T3-E1 preosteoblasts embedded in layer shaped alginate hydrogels were not observed. These results suggest that the obtained medical surfaces, based on the novel thiourea derivatives and magnetic nanoparticles with a polymeric shell could represent a promising alternative for the development of new and effective anti-infective strategies.
    Subject(s): Anti-Bacterial Agents - chemical synthesis ; Anti-Bacterial Agents - chemistry ; Anti-Bacterial Agents - pharmacology ; anti-biofilm ; benzamides ; Benzamides - chemical synthesis ; Benzamides - chemistry ; Benzamides - pharmacology ; Biofilms - drug effects ; Biofilms - growth & development ; core ; core/shell nanostructure ; Humans ; Iron Compounds - chemistry ; Iron Compounds - pharmacology ; Magnetic Resonance Spectroscopy ; magnetite ; Nanostructures - administration & dosage ; Nanostructures - chemistry ; Polyvinyls - chemical synthesis ; Polyvinyls - chemistry ; Polyvinyls - pharmacology ; Pseudomonas aeruginosa - drug effects ; Pseudomonas aeruginosa - growth & development ; Pyrrolidines - chemical synthesis ; Pyrrolidines - chemistry ; Pyrrolidines - pharmacology ; shell nanostructure ; Staphylococcus aureus - drug effects ; Staphylococcus aureus - growth & development ; thiourea derivatives
    ISSN: 1420-3049
    E-ISSN: 1420-3049
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
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  • 7
    Language: English
    In: Journal of clinical medicine, 2021-02-04, Vol.10 (4), p.587
    Description: Locally advanced head and neck cancer is a unique challenge for cancer management in the Covid-19 situation. The negative consequences of delaying radio-chemotherapy treatment make it necessary to prioritize these patients, the continuation of radiotherapy being indicated even if SARS-CoV-2 infection is confirmed in the case of patients with moderate and mild symptoms. For an early scenario, the standard chemo-radiotherapy using simultaneous integrated boost (SIB) technique is the preferred option, because it reduces the overall treatment time. For a late scenario with limited resources, hypo-fractionated treatment, with possible omission of chemotherapy for elderly patients and for those who have comorbidities, is recommended. Concurrent chemotherapy is controversial for dose values 〉2.4 Gy per fraction. The implementation of hypo-fractionated regimens should be based on a careful assessment of dose-volume constraints for organs at risks (OARs), using recommendations from clinical trials or dose conversion based on the linear-quadratic (LQ) model. Induction chemotherapy is not considered the optimal solution in this situation because of the risk of immunosuppression even though in selected groups of patients TPF regimen may bring benefits. Although the MACH-NC meta-analysis of chemotherapy in head and neck cancers did not demonstrate the superiority of induction chemotherapy over concurrent chemoradiotherapy, an induction regimen could be considered for cases with an increased risk of metastasis even in the case of a possible Covid-19 pandemic scenario.
    Subject(s): chemotherapy ; Covid-19 ; head and neck cancer ; non-surgical ; radiotherapy
    ISSN: 2077-0383
    E-ISSN: 2077-0383
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: Alma/SFX Local Collection
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  • 8
    Language: English
    In: Annals of nuclear medicine, 2021-09-01, Vol.35 (9), p.967-993
    Description: Keywords: Bone scan; Cardiac amyloidosis; Transthyretin cardiac amyloidosis; Transthyretin cardiac amyloidosis detection methods; Personalized medicine Cardiac amyloidosis is a protein deposition disease characterized by the infiltration of the myocardium and coronary arteries resulting in a progressive thickening of both ventricles, interatrial septum and atrioventricular valves, eventually leading to organ failure. It is a disease hard to diagnose, due to the lack of diagnostic investigations. However, development of new and more accurate examinations is undergoing. Endomyocardial biopsy is the gold standard investigation for this disease, but it has its limitations (invasive and not widely available). Other investigations may be able to detect the presence of cardiac amyloidosis but cannot specify the type involved. To that end, nuclear medicine through bone scanning offers a simple, non-invasive solution to detect, differentiate and diagnose transthyretin cardiac amyloidosis (ATTR) from other types of cardiac amyloidosis. In order to demonstrate the importance of bone scanning we will present a few methods of image processing based on literature and a personalized method, followed by a few important examples of positive cases. The aim of this review was to present the current methods of ATTR detection with emphasis on nuclear medicine bone scanning and its important place in the decision algorithm of the cardiologist for a personalized approach to this pathology. Author Affiliation: (1) Nuclear Medicine Laboratory, County Emergency Hospital "Sf. Spiridon", IaÈi, Romania (2) Cardiology Department, County Emergency Hospital "Sf. Spiridon", IaÈi, Romania (3) University of Medicine and Pharmacy U.M.F "Grigore T. Popa", IaÈi, Romania (4) Endocrinology Department, County Emergency Hospital "Sf. Spiridon", IaÈi, Romania (a) teodor_y_2005@yahoo.com Article History: Registration Date: 06/28/2021 Received Date: 12/29/2020 Accepted Date: 06/27/2021 Online Date: 07/17/2021 Byline:
    Subject(s): Algorithms ; Amyloidosis ; Cardiology ; Image processing
    ISSN: 0914-7187
    E-ISSN: 1864-6433
    Source: Alma/SFX Local Collection
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  • 9
    Language: English
    In: BMC infectious diseases, 2013-12-16, Vol.13 (S1), p.P81-P81
    Subject(s): Poster Presentation
    ISSN: 1471-2334
    E-ISSN: 1471-2334
    Source: BioMedCentral Open Access
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
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  • 10
    Language: English
    In: Experimental and therapeutic medicine, 2021-01, Vol.21 (1), p.81-81
    Description: Gestational diabetes mellitus is an important healthcare problem with serious implications both to the mother and to the foetus. The necessity of clear screening criteria for the pregnant woman and also identifying from an early stage the risk groups can be beneficial instruments for better management of gestational diabetes. The present report identify the main screening criteria for patients at risk for gestational diabetes and the therapeutic-nutritional therapy for women that have gestational diabetes. The different diagnostic criteria, as well as the new instruments through which these criteria can be applied, are still heterogeneous, and it is necessary to unify and promote them. The prevalence of gestational diabetes has significantly increased in recent years, and this has led to an increase in the direct and indirect costs of healthcare. Establishing the optimal time and initiating the correct treatment is critical to achieving glycemic control and to minimize the impact on fetal development and perinatal complications.
    Subject(s): Birth weight ; Body fat ; Care and treatment ; Children & youth ; Congenital diseases ; Diabetes in pregnancy ; Diagnosis ; Fasting ; Gestational diabetes ; gestational diabetes mellitus ; Glucose ; Insulin resistance ; management of gestational diabetes ; Mortality ; Obstetrics ; Peptides ; Pregnancy ; Review ; Risk factors ; screening ; treatment of gestational diabetes ; Womens health
    ISSN: 1792-0981
    E-ISSN: 1792-1015
    Source: Academic Search Ultimate
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