scholarly journals Long-Term Environmental Hypoxia Exposure and Haematopoietic Prolyl Hydroxylase-1 Deletion Do Not Impact Experimental Crohn’s Like Ileitis

Biology ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 887
Author(s):  
Cara De Galan ◽  
Martine De Vos ◽  
Pieter Hindryckx ◽  
Debby Laukens ◽  
Sophie Van Welden

Environmental hypoxia and hypoxia-induced signalling in the gut influence inflammatory bowel disease pathogenesis, however data is limited to colitis. Hence, we investigated the effect of environmental hypoxia and immune cell-specific deletion of oxygen sensor prolyl hydroxylase (PHD) 1 in a Crohn’s like ileitis mouse model. Therefore, 5-week-old C57/BL6 TNF∆ARE/+ mice and wildtype (WT) littermates were housed in normoxia (21% O2) or hypoxia (8% O2) for 10 weeks. Systemic inflammation was assessed by haematology. Distal ileal hypoxia was evaluated by pimonidazole staining. The ileitis degree was scored on histology, characterized via qPCR and validated in haematopoietic Phd1-deficient TNF∆ARE/+ mice. Our results demonstrated that hypoxia did not impact body weight evolution in WT and TNF∆ARE/+ mice. Hypoxia increased red blood cell count, haemoglobin, haematocrit and increased pimonidazole intensity in the ileum. Interestingly, hypoxia evoked an increase in circulatory monocytes, ileal mononuclear phagocytes and proinflammatory cytokine expression in WT mice. Despite these alterations, no histological or ileal gene expression differences could be identified between TNF∆ARE/+ mice housed in hypoxia versus normoxia nor between haematopoietic Phd1-deficient TNF∆ARE/+ and their WT counterparts. Therefore, we demonstrated for the first time that long-term environmental hypoxia or haematopoietic Phd1-deletion does not impact experimental ileitis development.

2015 ◽  
Vol 148 (4) ◽  
pp. S-176 ◽  
Author(s):  
Laura Targownik ◽  
Aruni Tennakoon ◽  
Harminder Singh ◽  
Zoann Nugent ◽  
Lisa Lix ◽  
...  

1970 ◽  
Vol 19 (1) ◽  
pp. 89-99
Author(s):  
K. Choudhary ◽  
M. Singh ◽  
M. S. Rathore ◽  
N. S. Shekhawat

This long term study demonstrates for the first time that it is possible to propagate embryogenic Vigna trilobata and to subsequently initiate the differentiation of embryos into complete plantlets. Initiation of callus was possible on 2,4-D. Somatic embryos differentiated on modified MS basal nutrient medium with 1.0 mg/l  of 2,4-D and 0.5 mg/l  of Kn. Sustained cell division resulted in globular and heart shape stages of somatic embryos. Transfer of embryos on to a fresh modified MS basal medium with 0.5 mg/l of Kn and 0.5 mg/l of GA3 helped them to attain maturation and germination. However, the propagation of cells, as well as the differentiation of embryos, were inhibited by a continuous application of these growth regulators. For this reason, a long period on medium lacking these growth regulators was necessary before the differentiation of embryos occurred again. The consequences for improving the propagation of embryogenic cultures in Vigna species are discussed. Key words: Pasture  legume, Vigna trilobata, Globular, Heart shape, somatic embryogenesis D.O.I. 10.3329/ptcb.v19i1.4990 Plant Tissue Cult. & Biotech. 19(1): 89-99, 2009 (June)


2017 ◽  
pp. 34-47
Author(s):  
Hoi Le Quoc ◽  
Nam Pham Xuan ◽  
Tuan Nguyen Anh

The study was targeted at developing a methodology for constructing a macroeconomic performance index at a provincial level for the first time in Vietnam based on 4 groups of measurements: (i) Economic indicators; (ii) oriented economic indicators; (iii) socio-economic indicators; and (iv) economic - social – institutional indicators. Applying the methodology to the 2011 - 2015 empirical data of all provinces in Vietnam, the research shows that the socio-economic development strategy implemented by those provinces did not provide balanced outcomes between growth and social objectives, sustainability and inclusiveness. Many provinces focused on economic growth at the cost of structural change, equality and institutional transformation. In contrast, many provinces were successful in improving equality but not growth. Those facts threaten the long-term development objectives of the provinces.


Author(s):  
O. D. Golyaeva ◽  
O. V. Kurashev ◽  
S. D. Knyazev ◽  
А. Yu. Bakhotskaya

The main goal of the scientific institution was and remains to improve the assortment of fruit and berry crops for the development of domestic horticulture. Black currant breeding at VNIISPK was started by A.F Tamarova and continued by the doctor of agricultural Sciences T.P.Ogoltsova and doctor of agricultural Sciences S.D. Knyazev. A long-term breeding program has been developed. The main goals of the program are to create black currant cultivars with continuous resistance to diseases, first of all powdery mildew, as wells resistance to pests, i.e. bud mite. As a result of the long-term work, over 40 black currant cultivars have been developed, 14 of them are zoned. Red currant breeding was led by the candidate of agricultural Sciences L.V. Bayanova; since 2001 the work has been continued by the candidate of agricultural Sciences O.D. Golyaeva. ‘Heinemanns Rote Spӓtlese’, the descendant of R. multiflorum Kit., was involved in the red currant breeding for the first time in Russia. On its genetic basis, a series of late maturing cultivars with long and dense racemes was created. At the Institute, in total 21cultivars of red currants have been developed, 13 of them are zoned. At present, red currant cultivars make up 25.5% of the zoned assortment in Russia. The first research on gooseberries was stated by V.P. Semakin and A.F Tamarova; since 1992 the systematic gooseberry breeding has been carried out by the candidate of agricultural Sciences O.V. Kurashev. On the basis of Grossularia robusta, we have created gooseberry forms that are resistant to powdery mildew and leaf spots. These forms are highly productive, weakly thorned, having bush habit suitable for mechanized harvest. The result of breeding activities was the transfer of 6 gooseberry cultivars to State agricultural testing: ‘Solnechny Zaychik’, ‘Nekrasovsky’, ‘Yupiter’, ‘Zemlianichny’, ‘Moryachok’ and ‘Discovery’.


2019 ◽  
Vol 25 (1) ◽  
pp. 57-63 ◽  
Author(s):  
Clara Yzet ◽  
Stacy S. Tse ◽  
Maia Kayal ◽  
Robert Hirten ◽  
Jean-Frédéric Colombel

The emergence of biologic therapies has revolutionized the management of inflammatory bowel disease (IBD) by halting disease progression, increasing remission rates and improving long-term clinical outcomes. Despite these well-described benefits, many patients are reluctant to commence therapy due to drug safety concerns. Adverse events can be detected at each stage of drug development and during the post-marketing period. In this article, we review how to best assess the safety parameters of new IBD medications, from the earliest stage of development to population-based registries, with a focus on the special populations often excluded from the evaluation process.


2020 ◽  
Vol 20 (11) ◽  
pp. 875-886
Author(s):  
Yingyi Wang ◽  
Bao Jin ◽  
Na Zhou ◽  
Zhao Sun ◽  
Jiayi Li ◽  
...  

Background:: Neoantigens are newly formed antigens that have not been previously recognized by the immune system. They may arise from altered tumor proteins that form as a result of mutations. Although neoantigens have recently been linked to antitumor immunity in long-term survivors of cancers, such as melanoma and colorectal cancer, their prognostic and immune-modulatory role in many cancer types remains undefined. Objective: The purpose of this study is to identify prognostic markers for long-term extrahepatic cholangiocarcinoma (EHCC) survival. Methods: We investigated neoantigens in EHCC, a rare, aggressive cancer with a 5-year overall survival rate lower than 10%, using a combination of whole-exome sequencing (WES), RNA sequencing (RNA-seq), computational biophysics, and immunohistochemistry. Results: : Our analysis revealed a decreased neutrophil infiltration-related trend of high-quality neoantigen load with IC50 <500 nM (r=-0.445, P=0.043). Among 24 EHCC patients examined, we identified four long-term survivors with WDFY3 neoantigens and none with WDFY3 neoantigens in the short-term survivors. The WDFY3 neoantigens are associated with a lower infiltration of neutrophils (p=0.013), lower expression of CCL5 (p=0.025), CXCL9 (p=0.036) and TIGIT (p=0.016), and less favorable prognosis (p=0.030). In contrast, the prognosis was not significantly associated with tumor mutation burden, neoantigen load, or immune cell infiltration. Conclusion:: We suggest that the WDFY3 neoantigens may affect prognosis by regulating antitumor immunity and that the WDFY3 neoantigens may be harnessed as potential targets for immunotherapy of EHCC.


2020 ◽  
Vol 15 ◽  
Author(s):  
Maria Carla Di Paolo ◽  
Cristiano Pagnini ◽  
Maria Giovanna Graziani

: Inflammatory bowel diseases (IBDs) are chronic conditions characterized by unknown etiology and pathogenesis with deregulation of mucosal immunity. Among possible treatments, corticosteroids, already available from the 50’, are still the mainstay of treatment for moderate-severe disease. Nonetheless, the use of steroids is still largely empirical and solid evidence about therapeutic schemes are lacking. Moreover, due to the important side-effects and for the unsatisfactory impact on long-term natural history of disease, the steroid sparing has become an important therapeutic goal in IBD management. Besides conventional steroids, the so called “low bioavailability” steroids, which are steroids with high affinity for peripheral receptors and elevated hepatic first-pass metabolism, have demonstrated efficacy and more favorable safety profile. In the present review of the literature evidence of efficacy and safety of conventional and low bioavailability steroids in IBD patients are evaluated, and practical suggestions for a correct use in clinical practice are presented according to the current clinical guidelines.


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