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31.
Fang Jiang Chengsheng Ju Chuan-Guo Guo Ka Shing Cheung Bofei Li Simon Y. K. Law Wallis C. Y. Lau Wai K. Leung 《Helicobacter》2023,28(4):e12990
Background
To investigate risks of hospitalization for upper gastrointestinal bleeding (UGIB) in H. pylori-eradicated patients newly started on warfarin or direct oral anti-coagulants (DOACs).Methods
We identified all patients who had previously received H. pylori eradication therapy or were found to have no H. pylori on endoscopy and were then newly started on warfarin or DOACs from a population-based electronic healthcare database. Primary analysis was the risk of UGIB between warfarin and DOACs users in H. pylori-eradicated patients. Secondary analysis included the UGIB risk between H. pylori-eradicated and H. pylori-negative patients who were newly started on warfarin or DOACs. The hazard ratio (HR) of UGIB was approximated by pooled logistic regression model incorporating the inverse propensity of treatment weightings with time-varying covariables.Results
Among H. pylori-eradicated patients, DOACs had a significantly lower risk of UGIB (HR: 0.26, 95% CI 0.09–0.71) compared with warfarin. In particular, lower UGIB risks with DOACs were observed among older ( ≥ 65 years) patients, female, those without a history of UGIB or peptic ulcer, or ischemic heart disease, and non-users of acid-suppressive agents or aspirin. Secondary analysis showed no significant difference in UGIB risk between H. pylori-eradicated and H. pylori-negative patients newly started on warfarin (HR: 0.63,95% CI 0.33–1.19) or DOACs (HR: 1.37, 95% CI 0.45–4.22).Conclusions
In H. pylori-eradicated patients, new users of DOACs had a significantly lower risk of UGIB than new warfarin users. Furthermore, the risk of UGIB in new warfarin or DOACs users was comparable between H. pylori-eradicated and H. pylori-negative patients. 相似文献32.
Abstract: CSF glutamine concentrations were studied in 12 patients with benign brain tumors (meningioma, craniopharyngioma, or osteofibroma), 12 patients with malignant brain tumors (astrocytoma, medulloblastoma, pinealoblastoma, or chondrosarcoma), 9 patients with non-cerebral tumors, and a reference group of 24 patients. The mean ± SD levels in the benign tumor group (424 ± 124 μ M ) were significantly lower (p < 0.0004) than those in the reference group (642 ± 195 μ M ). There was no significant difference between the CSF glutamine concentrations in the malignant cerebral tumor group (643 ± 210 μ M ) or noncerebral tumor group (599 ± 127 μ M ) and those in the reference group. In patients with benign brain tumors there was indication of an inverse linear relationship between the logarithm of CSF glutamine concentration and tumor diameter. 相似文献
33.
Mathupala SP Colen CB Parajuli P Sloan AE 《Journal of bioenergetics and biomembranes》2007,39(1):73-77
Metabolic aberrations in the form of altered flux through key metabolic pathways are primary hallmarks of many malignant tumors.
Primarily the result of altered isozyme expression, these adaptations enhance the survival and proliferation of the tumor
at the expense of surrounding normal tissue. Consequently, they also expose a unique set of targets for tumor destruction
while sparing healthy tissues. Despite this fact, development of drugs to directly target such altered metabolic pathways
of malignant tumors has been under-investigated until recently. One such target is the ultimate step of glycolysis, which,
as expected, presents itself as a metabolic aberration in most malignant tumors. Termed “aerobic glycolysis” due to abnormal
conversion of pyruvic acid to lactic acid even under normoxia, the altered metabolism requires these tumors to rapidly efflux
lactic acid to the microenvironment in order to prevent poisoning themselves. Thus, exposed is a prime “choke-point” to target
these highly malignant, frequently chemo- and radio- resistant tumors. This review will focus on current outcomes in targeting
lactate efflux in such tumors using glioma as a model, an ongoing project in our laboratory for the past half-decade, as well
as supporting evidence from recent studies by others on targeting this “tail-end” of glycolysis in other tumor models. 相似文献
34.
Walter M Lucet IS Patel O Broughton SE Bamert R Williams NK Fantino E Wilks AF Rossjohn J 《Journal of molecular biology》2007,367(3):839-847
c-Fms, a member of the Platelet-derived Growth Factor (PDGF) receptor family of receptor tyrosine kinases (RTKs), is the receptor for macrophage colony stimulating factor (CSF-1) that regulates proliferation, differentiation and survival of cells of the mononuclear phagocyte lineage. Abnormal expression of c-fms proto-oncogene is associated with a significant number of human pathologies, including a variety of cancers and rheumatoid arthritis. Accordingly, c-Fms represents an attractive therapeutic target. To further understand the regulation of c-Fms, we determined the 2.7 A resolution crystal structure of the cytosolic domain of c-Fms that comprised the kinase domain and the juxtamembrane domain. The structure reveals the crucial inhibitory role of the juxtamembrane domain (JM) that binds to a hydrophobic site immediately adjacent to the ATP binding pocket. This interaction prevents the activation loop from adopting an active conformation thereby locking the c-Fms kinase into an autoinhibited state. As observed for other members of the PDGF receptor family, namely c-Kit and Flt3, three JM-derived tyrosine residues primarily drive the mechanism for autoinhibition in c-Fms, therefore defining a common autoinhibitory mechanism within this family. Moreover the structure provides an understanding of c-Fms inhibition by Gleevec as well as providing a platform for the development of more selective inhibitors that target the inactive conformation of c-Fms kinase. 相似文献
35.
Genetic deletion in mice of pregnancy-associated plasma protein A (PAPP-A), a recently identified metalloproteinase in the insulin-like growth factor system, extends by 30-40% both mean and maximum lifespan with no reduction in food intake or secondary endocrine abnormalities. Furthermore, these mice have markedly reduced incidence of spontaneous tumors. The findings implicate PAPP-A as a critical regulator of lifespan and age-related diseases, and suggest PAPP-A as a possible target to promote longevity. 相似文献
36.
Kelly S Swanson Scot E Dowd Jan S Suchodolski Ingmar S Middelbos Brittany M Vester Kathleen A Barry Karen E Nelson Manolito Torralba Bernard Henrissat Pedro M Coutinho Isaac KO Cann Bryan A White George C Fahey Jr 《The ISME journal》2011,5(4):639-649
This study is the first to use a metagenomics approach to characterize the phylogeny and functional capacity of the canine gastrointestinal microbiome. Six healthy adult dogs were used in a crossover design and fed a low-fiber control diet (K9C) or one containing 7.5% beet pulp (K9BP). Pooled fecal DNA samples from each treatment were subjected to 454 pyrosequencing, generating 503 280 (K9C) and 505 061 (K9BP) sequences. Dominant bacterial phyla included the Bacteroidetes/Chlorobi group and Firmicutes, both of which comprised ∼35% of all sequences, followed by Proteobacteria (13–15%) and Fusobacteria (7–8%). K9C had a greater percentage of Bacteroidetes, Fusobacteria and Proteobacteria, whereas K9BP had greater proportions of the Bacteroidetes/Chlorobi group and Firmicutes. Archaea were not altered by diet and represented ∼1% of all sequences. All archaea were members of Crenarchaeota and Euryarchaeota, with methanogens being the most abundant and diverse. Three fungi phylotypes were present in K9C, but none in K9BP. Less than 0.4% of sequences were of viral origin, with >99% of them associated with bacteriophages. Primary functional categories were not significantly affected by diet and were associated with carbohydrates; protein metabolism; DNA metabolism; cofactors, vitamins, prosthetic groups and pigments; amino acids and derivatives; cell wall and capsule; and virulence. Hierarchical clustering of several gastrointestinal metagenomes demonstrated phylogenetic and metabolic similarity between dogs, humans and mice. More research is required to provide deeper coverage of the canine microbiome, evaluate effects of age, genetics or environment on its composition and activity, and identify its role in gastrointestinal disease. 相似文献
37.
Larisa Obukhova Tatiana Kopytova Elena Murach Natalya Shchelchkova Claudia Kontorshchikova Igor Medyanik Natalia Orlinskaya Artem Grishin Michael Kontorshchikov Dariya Badanina 《Current issues in molecular biology》2022,44(12):6439
This research was aimed at investigating the features of free radical activity and the parameters of glutathione metabolism in tumor tissues and the peritumoral zone at different degrees of glial tumor anaplasia. We analyzed postoperative material from 20 patients with gliomas of different degrees of anaplasia. The greatest differences compared to adjacent noncancerous tissues were found in the tumor tissue: an increased amount of glutathione and glutathione-related enzymes at Grades I and II, and a decrease of these parameters at Grades III and IV. For the peritumoral zone of Grades I and II, the indices changed in different directions, while for Grades III and IV, they occurred synchronously with the tumor tissue changes. For Low Grade and High Grade gliomas, opposite trends were revealed regarding changes in the level of glutathione and the enzymes involved in its metabolism and in the free radical activity in the peritumoral zone. The content of glutathione and the enzymes involved in its metabolism decreased with the increasing degree of glioma anaplasia. In contrast, free radical activity increased. The glutathione system is an active participant in the antioxidant defense of the body and can be used to characterize the cell condition of gliomas at different stages of tumor development. 相似文献
38.
39.
Au Yeung KJ Smith A Zhao A Madden KB Elfrey J Sullivan C Levander O Urban JF Shea-Donohue T 《Experimental parasitology》2005,109(4):201-208
The effects of deficiencies in the antioxidant nutrients, vitamin E and selenium, on the host response to gastrointestinal nematode infection are unknown. The aim of the study was to determine the effect of antioxidant deficiencies on nematode-induced alterations in intestinal function in mice. BALB/c mice were fed control diets or diets deficient in selenium or vitamin E and the response to a secondary challenge inoculation with Heligmosomoides polygyrus was determined. Egg and worm counts were assessed to determine host resistance. Sections of jejunum were mounted in Ussing chambers to measure changes in permeability, absorption, and secretion, or suspended in organ baths to determine smooth muscle contraction. Both selenium and vitamin E deficient diets reduced resistance to helminth infection. Vitamin E, but not selenium, deficiency prevented nematode-induced decreases in glucose absorption and hyper-contractility of smooth muscle. Thus, vitamin E status is an important factor in the physiological response to intestinal nematode infection and may contribute to antioxidant-dependent protective mechanisms in the small intestine. 相似文献
40.
Gorla L Cantù M Miccichè F Patelli C Mondellini P Pierotti MA Bongarzone I 《Cellular signalling》2006,18(12):2272-2282
We report the identification of proteins induced in response to RET/PTC2, an oncogene implicated in thyroid cancers. Anti-phosphotyrosine antibody affinity resin was used to purify Tyr(P)-containing and interacting proteins from 293T and NIH3T3 cells which were transfected with kinase active or inactive RET/PTC and RETMEN2 oncogenes. Proteins were separated by one-dimensional SDS-PAGE, extracted by in-gel digestion, and identified by MALDI-TOF peptide mass fingerprinting. The expression and tyrosine phosphorylation of Sam68, a protein implicated in mRNA nucleocytoplasmic translocation and splicing, were further examined in RET-transfected cells and thyroid tumors. Of relevance, cells transfected with RETMEN2B examined for anti-phosphotyrosine bound proteins, showed other proteins implicated in splicing: DEAD-box p68 RNA helicase, SYNCRIP, and hnRNP K. Western blotting analysis suggested that these proteins are singularly tyrosine phosphorylated in RETMEN2B-transfected cells, and that they constitutively bind with Sam68. The study concludes that regulation of splicing factors is likely to be important in RET-mediated thyroid carcinogenesis. 相似文献