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81.
Catarina Macedo-Silva Vera Miranda-Gonalves Ana Lameirinhas Joana Lencart Alexandre Pereira Joo Lobo Rita Guimares Ana Teresa Martins Rui Henrique Isabel Bravo Carmen Jernimo 《Cell death & disease》2020,11(12)
Esophageal squamous cell carcinoma (ESCC), the most frequent esophageal cancer (EC) subtype, entails dismal prognosis. Hypoxia, a common feature of advanced ESCC, is involved in resistance to radiotherapy (RT). RT response in hypoxia might be modulated through epigenetic mechanisms, constituting novel targets to improve patient outcome. Post-translational methylation in histone can be partially modulated by histone lysine demethylases (KDMs), which specifically removes methyl groups in certain lysine residues. KDMs deregulation was associated with tumor aggressiveness and therapy failure. Thus, we sought to unveil the role of Jumonji C domain histone lysine demethylases (JmjC-KDMs) in ESCC radioresistance acquisition. The effectiveness of RT upon ESCC cells under hypoxic conditions was assessed by colony formation assay. KDM3A/KDM6B expression, and respective H3K9me2 and H3K27me3 target marks, were evaluated by RT-qPCR, Western blot, and immunofluorescence. Effect of JmjC-KDM inhibitor IOX1, as well as KDM3A knockdown, in in vitro functional cell behavior and RT response was assessed in ESCC under hypoxic conditions. In vivo effect of combined IOX1 and ionizing radiation treatment was evaluated in ESCC cells using CAM assay. KDM3A, KDM6B, HIF-1α, and CAIX immunoexpression was assessed in primary ESCC and normal esophagus. Herein, we found that hypoxia promoted ESCC radioresistance through increased KDM3A/KDM6B expression, enhancing cell survival and migration and decreasing DNA damage and apoptosis, in vitro. Exposure to IOX1 reverted these features, increasing ESCC radiosensitivity and decreasing ESCC microtumors size, in vivo. KDM3A was upregulated in ESCC tissues compared to the normal esophagus, associating and colocalizing with hypoxic markers (HIF-1α and CAIX). Therefore, KDM3A upregulation in ESCC cell lines and primary tumors associated with hypoxia, playing a critical role in EC aggressiveness and radioresistance. KDM3A targeting, concomitant with conventional RT, constitutes a promising strategy to improve ESCC patients’ survival.Subject terms: Predictive markers, Cancer 相似文献
82.
Mafalda C. O. Figueiredo Susana A. L. Lobo Sara H. Sousa Fábio P. Pereira Judy D. Wall Lígia S. Nobre Lígia M. Saraiva 《Journal of bacteriology》2013,195(11):2684-2690
Desulfovibrio species are Gram-negative anaerobic sulfate-reducing bacteria that colonize the human gut. Recently, Desulfovibrio spp. have been implicated in gastrointestinal diseases and shown to stimulate the epithelial immune response, leading to increased production of inflammatory cytokines by macrophages. Activated macrophages are key cells of the immune system that impose nitrosative stress during phagocytosis. Hence, we have analyzed the in vitro and in vivo responses of Desulfovibrio vulgaris Hildenborough to nitric oxide (NO) and the role of the hybrid cluster proteins (HCP1 and HCP2) and rubredoxin oxygen oxidoreductases (ROO1 and ROO2) in NO protection. Among the four genes, hcp2 was the gene most highly induced by NO, and the hcp2 transposon mutant exhibited the lowest viability under conditions of NO stress. Studies in murine macrophages revealed that D. vulgaris survives incubation with these phagocytes and triggers NO production at levels similar to those stimulated by the cytokine gamma interferon (IFN-γ). Furthermore, D. vulgaris
hcp and roo mutants exhibited reduced viability when incubated with macrophages, revealing that these gene products contribute to the survival of D. vulgaris during macrophage infection. 相似文献
83.
Angiotensin II acts on adrenal glomerulosa cells to induce the phospholipase C-mediated generation of inositol trisphosphate and sn-1,2-diacylglycerol as the major products of inositol phospholipid breakdown. This last product is known to activate protein kinase C, but its role in the action of angiotensin II on steroidogenesis has not been defined. We report herein that, in bovine adrenal glomerulosa cells, protein kinase C activators, such as phorbol 12,13-dibutyrate, 12-O-tetradecanoylphorbol-13-acetate, mezerein and sn 1,2 oleoyl acetoylglycerol, each failed to increase steroidogenesis. These results contrast with our recent report on the enhancement of aldosterone output by sn-1,2-dioctanoylglycerol (DiC8) [J. Steroid Biochem. 35 (1990) 19-33]. In addition, the difference between DiC8 and the other protein kinase activators was also observed in the pattern of 86Rb efflux from preloaded glomerulosa cells; only DiC8 mimicked the effect of angiotensin II on ion fluxes. Furthermore, staurosporine, a potent inhibitor of protein kinase C, was capable of amplifying the aldosterone output induced by a maximally effective concentration of DiC8 or angiotensin II. These data suggest that the effect of the cell permeant DiC8 on aldosterone biosynthesis either is not mediated by protein kinase C activation, or is mediated by a phorbol ester-insensitive isoenzyme of protein kinase C. 相似文献
84.
Helena Santos-Rosa Gonzalo Millán-Zambrano Namshik Han Tommaso Leonardi Marie Klimontova Simona Nasiscionyte Luca Pandolfini Kostantinos Tzelepis Till Bartke Tony Kouzarides 《Molecular cell》2021,81(13):2793-2807.e8
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85.
Leonardo Mata Helena Gaspar Fátima Justino Rui Santos 《Journal of applied phycology》2011,23(5):827-832
The genus Asparagopsis is a prolific source of halogenated metabolites. Due to its commercial applications, it has been intensively cultivated in
southern Portugal. In the present study, we assess if the internal levels of the major halogenated metabolites (bromoform
and dibromoacetic acid) in Asparagopsis taxiformis can be increased with hydrogen peroxide (H2O2) addition. Previous studies with red algae showed that the production/release of bromoform can be enhanced by exogenously
supplying H2O2. However, no study has assessed if H2O2 supply enhances the content of secondary metabolites within the biomass. This detail is important as the objective of the
proposed research is to enhance the content of these valuable metabolites in the produced biomass. Both the activity of the
haloperoxidase enzyme and the metabolite content were assessed on short-term and long-term incubation periods to H2O2. To determine the susceptibility of A. taxiformis photosynthetic performance to the imposed oxidative stress, the in vivo fluorescence of photosystem II was monitored. A. taxiformis was shown to be physiologically vulnerable to H2O2, given the observed decrease of the maximum quantum yield of photosynthesis (F
v/F
m). Contrary to what was expected, the presence of H2O2 inhibited the activity of the iodoperoxidase enzyme. Nevertheless, the extracted halogenated metabolites were higher over
the first hours of exposure to H2O2, decreasing after 48 h. These results are probably related to the prosthetic group of the halogenated enzyme in A. taxiformis and the long-term oxidative stress damage of H2O2 exposure. Considering the objective of the proposed research, addition of H2O2 to the cultures, prior (3 h) to biomass harvesting, increases the metabolite content. 相似文献
86.
87.
A F Borges 《Plastic and reconstructive surgery》1984,73(1):144-150
The seven best known skin tension lines are presented. The directions they convey are schematically compared with those of the relaxed skin tension lines. Commentaries and discussion by the author are given in order to help the reader arrive at his or her own conclusions on which directions his or her incisions should take so as to obtain the best scarring. 相似文献
88.
Beatriz Pereira Moreno Gislaine Cristiane Mantovanelli Letycia Lopes Ricardo Adriano Antnio Silva Rubem Silvrio De Oliveira Emy Luiza Ishii‐Iwamoto Maria Helena Sarragiotto Debora Cristina Baldoqui 《化学与生物多样性》2020,17(3)
Studies of the phytotoxic effects between plants can be a crucial tool in the discovery of innovative compounds with herbicide potential. In this sense, we can highlight ruzigrass (Urochloa ruziziensis), which is traditionally used in the crop rotation system in order to reduce weed emergence. The aim of this work was to characterize the secondary metabolites of ruzigrass and to evaluate its phytotoxic effects. In total, eight compounds were isolated: friedelin, oleanolic acid, α‐amyrin, 1‐dehydrodiosgenone, sitosterol and stigmasterol glycosides, tricin and p‐coumaric acid. Phytotoxic effects of the crude methanolic extract and fractions of ruzigrass were assessed using germination rate, initial seedling growth, and biomass of Bidens pilosa, Euphorbia heterophylla and Ipomoea grandifolia. Chemometric analysis discriminated the weed species into three groups, and B. pilosa was the most affected by fractions of ruzigrass. The phytotoxic activities of 1‐dehydrodiosgenone, tricin, and p‐coumaric acid are also reported, and p‐coumaric acid and 1‐dehydrodiosgenone were active against B. pilosa. 相似文献
89.
Josephine Joy Hubloher Sabine Zeidler Pedro Lamosa Helena Santos Beate Averhoff Volker Müller 《Environmental microbiology》2020,22(12):5156-5166
The stress protectant trehalose is synthesized in Acinetobacter baumannii from UPD-glucose and glucose-6-phosphase via the OtsA/OtsB pathway. Previous studies proved that deletion of otsB led to a decreased virulence, the inability to grow at 45°C and a slight reduction of growth at high salinities indicating that trehalose is the cause of these phenotypes. We have questioned this conclusion by producing ∆otsA and ∆otsBA mutants and studying their phenotypes. Only deletion of otsB, but not deletion of otsA or otsBA, led to growth impairments at high salt and high temperature. The intracellular concentrations of trehalose and trehalose-6-phosphate were measured by NMR or enzymatic assay. Interestingly, none of the mutants accumulated trehalose any more but the ∆otsB mutant with its defect in trehalose-6-phosphate phosphatase activity accumulated trehalose-6-phosphate. Moreover, expression of otsA in a ∆otsB background under conditions where trehalose synthesis is not induced led to growth inhibition and the accumulation of trehalose-6-phosphate. Our results demonstrate that trehalose-6-phosphate affects multiple physiological activities in A. baumannii ATCC 19606. 相似文献
90.
Henrik Gislason Jeremy Collie Brian R. MacKenzie Anders Nielsen Maria de Fatima Borges Teresa Bottari Corina Chaves Andrey V. Dolgov Jakov Dul
i Daniel Duplisea Heino O. Fock Didier Gascuel Luís Gil de Sola Jan Geert Hiddink Remment ter Hofstede Igor Isajlovi Jnas Pll Jonasson Ole Jrgensen Kristjn Kristinsson Gudrun Marteinsdottir Hicham Masski Sanja Mati‐Skoko Mark R. Payne Melita Peharda Jakup Reinert Jn Slmundsson Cristina Silva Lilja Stefansdottir Francisco Velasco Nedo Vrgo
《Global Ecology and Biogeography》2020,29(5):842-856