151 research outputs found
Antibiotic use during pregnancy increases offspring asthma severity in a dose‐dependent manner
Background: The use of antibiotics during pregnancy is associated with increased allergic asthma risk in the offspring, and given that approximately 25% of pregnant women are prescribed antibiotics, it is important to understand the mechanisms contributing to this phenomenon. Currently, there are no studies that directly test this association experimentally. Our objective was to develop a mouse model in which antibiotic treatment during pregnancy results in increased offspring asthma susceptibility.
Methods: Pregnant mice were treated daily from gestation day 8-17 with an oral solution of the antibiotic vancomycin, and three concentrations were tested. At weaning, offspring were subjected to an adjuvant-free experimental asthma protocol using ovalbumin as an allergen. The composition of the gut microbiome was determined in mothers and offspring with samples collected from five different time points; shortchain fatty acids were also analyzed in allergic offspring.
Results: We found that maternal antibiotic treatment during pregnancy was associated with increased offspring asthma severity in a dose-dependent manner. Furthermore, maternal vancomycin treatment during pregnancy caused marked changes in the gut microbiome composition in both mothers and pups at several different time points. The increased asthma severity and intestinal microbiome changes in pups were also associated with significantly decreased cecal short-chain fatty acid concentrations.
Conclusion: Consistent with the "Developmental Origins Hypothesis," our results confirm that exposure to antibiotics during pregnancy shapes the neonatal intestinal environment and increases offspring allergic lung inflammation
Enhanced neuronal Met signalling levels in ALS mice delay disease onset
Signalling by receptor tyrosine kinases (RTKs) coordinates basic cellular processes during development and in adulthood. Whereas aberrant RTK signalling can lead to cancer, reactivation of RTKs is often found following stress or cell damage. This has led to the common belief that RTKs can counteract degenerative processes and so strategies to exploit them for therapy have been extensively explored. An understanding of how RTK stimuli act at cellular levels is needed, however, to evaluate their mechanism of therapeutic action. In this study, we genetically explored the biological and functional significance of enhanced signalling by the Met RTK in neurons, in the context of a neurodegenerative disease. Conditional met-transgenic mice, namely Rosa26LacZ−stop−Met, have been engineered to trigger increased Met signalling in a temporal and tissue-specific regulated manner. Enhancing Met levels in neurons does not affect either motor neuron (MN) development or maintenance. In contrast, increased neuronal Met in amyotrophic lateral sclerosis (ALS) mice prolongs life span, retards MN loss, and ameliorates motor performance, by selectively delaying disease onset. Thus, our studies highlight the properties of RTKs to counteract toxic signals in a disease characterized by dysfunction of multiple cell types by acting in MNs. Moreover, they emphasize the relevance of genetically assessing the effectiveness of agents targeting neurons during ALS evolution
Human surfactant protein D alters oxidative stress and HMGA1 expression to induce p53 apoptotic pathway in eosinophil leukemic cell line
This article is made available through the Brunel Open Access Publishing Fund. Copyright: © 2013 Mahajan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Surfactant protein D (SP-D), an innate immune molecule, has an indispensable role in host defense and regulation of
inflammation. Immune related functions regulated by SP-D include agglutination of pathogens, phagocytosis,
oxidative burst, antigen presentation, T lymphocyte proliferation, cytokine secretion, induction of apoptosis and
clearance of apoptotic cells. The present study unravels a novel ability of SP-D to reduce the viability of leukemic
cells (eosinophilic leukemic cell line, AML14.3D10; acute myeloid leukemia cell line, THP-1; acute lymphoid leukemia
cell lines, Jurkat, Raji; and human breast epithelial cell line, MCF-7), and explains the underlying mechanisms. SP-D
and a recombinant fragment of human SP-D (rhSP-D) induced G2/M phase cell cycle arrest, and dose and timedependent
apoptosis in the AML14.3D10 eosinophilic leukemia cell line. Levels of various apoptotic markers viz.
activated p53, cleaved caspase-9 and PARP, along with G2/M checkpoints (p21 and Tyr15 phosphorylation of cdc2)
showed significant increase in these cells. We further attempted to elucidate the underlying mechanisms of rhSP-D
induced apoptosis using proteomic analysis. This approach identified large scale molecular changes initiated by SPD
in a human cell for the first time. Among others, the proteomics analysis highlighted a decreased expression of
survival related proteins such as HMGA1, overexpression of proteins to protect the cells from oxidative burst, while a
drastic decrease in mitochondrial antioxidant defense system. rhSP-D mediated enhanced oxidative burst in
AML14.3D10 cells was confirmed, while antioxidant, N-acetyl-L-cysteine, abrogated the rhSP-D induced apoptosis.
The rhSP-D mediated reduced viability was specific to the cancer cell lines and viability of human PBMCs from
healthy controls was not affected. The study suggests involvement of SP-D in host’s immunosurveillance and
therapeutic potential of rhSP-D in the eosinophilic leukemia and cancers of other origins.Department of Biotechnology, Indi
Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a tissue biomarker for detection of early Hepatocellular carcinoma in patients with cirrhosis
Heterogeneous nuclear ribonucleoprotein K is over expressed, aberrantly localised and is associated with poor prognosis in colorectal cancer
Heterogeneous ribonucleoprotein K (hnRNP K) is a member of the hnRNP family which has several different cellular roles including transcription, mRNA shuttling, RNA editing and translation. Several reports implicate hnRNP K having a role in tumorigenesis, for instance hnRNP K increases transcription of the oncogene c-myc and hnRNP K expression is regulated by the p53/MDM 2 pathway. In this study comparing normal colon to colorectal cancer by proteomics, hnRNP K was identified as being overexpressed in this type of cancer. Immunohistochemistry with a monoclonal antibody to hnRNP K (which we developed) on colorectal cancer tissue microarray, confirmed that hnRNP K was overexpressed in colorectal cancer (P<0.001) and also showed that hnRNP K had an aberrant subcellular localisation in cancer cells. In normal colon hnRNP K was exclusively nuclear whereas in colorectal cancer the protein localised both in the cytoplasm and the nucleus. There were significant increases in both nuclear (P=0.007) and cytoplasmic (P=0.001) expression of hnRNP K in Dukes C tumours compared with early stage tumours. In Dukes C patient's good survival was associated with increased hnRNP K nuclear expression (P=0.0093). To elaborate on the recent observation that hnRNP K is regulated by p53, the expression profiles of these two proteins were also analysed. There was no correlation between hnRNP K and p53 expression, however, patients who presented tumours that were positive for hnRNP K and p53 had a poorer survival outcome (P=0.045)
Lipidna peroksidacija i aktivnost antioksidativnih enzima u eritrocitima radnika profesionalno izloženih aluminiju
Current research indicates that lipid peroxidation could have a role in aluminium toxicity. The aim of this study was to asses lipid peroxidation and antioxidative enzyme activity in erythrocytes of workers occupationally exposed to aluminium. We investigated a group of 59 workers (Al group) exposed to aluminium fumes (contamination factor F=8.07 to 13.47, national maximal allowed concentration value is 2 mg m-3). The control group (C group) consisted of 75 subjects employed in lime production who had not been occupationally exposed to aluminium or any known toxic substance. Erythrocyte aluminium concentrations were significantly higher in the exposed group than controls [Al group (8.41±3.66) µg L-1, C group (5.60±0.86) µg L-1, p<0.001]. In the Al group, erythrocyte malondialdehyde concentration was also significantly higher [Al group (189.59±81.27) µmol L-1, C group (105.21±49.62) µmol L-1, p<0.001] and antioxidative enzyme activity reduced for glucoso-6-phosphatedehydrogenase [Al group (5.05±1.70) IU g-1 Hb, C group (12.53±4.12) IU g-1 Hb, p<0.001], glutathione reductase [Al group (1.41±0.56) IU g-1 Hb, C group (1.89±0.57) IU g-1 Hb, p<0.001], glutathione peroxidase [Al group (12.37±5.76) IU g-1 Hb, C group (15.54±4.85) IU g-1 Hb, p<0.001], catalase [Al group (116.76±26.60) IU g-1 Hb, C group (158.81±71.85) IU g-1 Hb, p<0.001] and superoxide dismutase [Al group (1175.8±149.9) IU mg-1 Hb, C group (1377.9±207.5) IU mg-1 Hb, p<0.001].Rezultati suvremenih istraživanja pokazuju da lipidna peroksidacija može imati važnu ulogu u toksičnosti aluminija. Cilj istraživanja bio je da se ispita lipidna peroksidacija i aktivnost antioksidativnih enzima u eritrocitima kod radnika profesionalno izloženih aluminiju. Ispitivanjem je obuhvaćena skupina od 59 radnika (Al skupina) profesionalno izloženih aluminiju (faktor onečišćenja F=8,07 do 13,47, nacionalna maksimalno dopuštena koncentracija je 2 mg m-3). Kontrolna skupina sastojala se od 75 osoba zaposlenih u proizvodnji vapna koje nikada nisu bile profesionalno izložene aluminiju ni drugim toksičnim tvarima. U skupini izloženoj aluminiju utvrđene su statistički signifikantno više koncentracije aluminija u eritrocitima nego u kontrolnoj skupini [Al skupina (8,41±3,66) µg L-1, kontrolna skupina (5,60±0,86) µg L-1, p<0,001]. U Al skupini utvrđene su statistički značajno više koncentracije malondialdehida u eritrocitima [Al skupina (189,59±81,27) µmol L-1, kontrolna skupina (105,21±49,62) µmol L-1, p<0,001]. Također, u Al skupini utvrđene su i statistički značajno niže aktivnosti antioksidativnih enzima u eritrocitima: glukozo- 6-fosfatdehidrogenaza [Al skupina (5,05±1,70) IU g-1 Hb, kontrolna skupina (12,53±4,12) IU g-1 Hb, p<0,001], glutationreduktaza [Al skupina (1,41±0,56) IU g-1 Hb, kontrolna skupina (1,89±0,57) IU g-1 Hb, p<0,001], glutationperoksidaza [Al skupina (12,37±5,76) IU g-1 Hb, kontrolna skupina (15,54±4,85) IU g-1 Hb, p<0,001], katalaza [Al skupina (116,76±26,60) IU g-1 Hb, kontrolna skupina (158,81±71,85) IU g-1 Hb, p<0,001] i superoksiddizmutaza [Al skupina (1175,8±149,9) IU mg-1 Hb, kontrolna skupina (1377,9±207,5) IU mg-1 Hb, p<0,001]
Signals: I. Survey description
SIGNALS, the Star formation, Ionized Gas, and Nebular Abundances Legacy Survey, is a large observing programme designed to investigate massive star formation and H II regions in a sample of local extended galaxies. The programme will use the imaging Fourier transform spectrograph SITELLE at the Canada–France–Hawaii Telescope. Over 355 h (54.7 nights) have been allocated beginning in fall 2018 for eight consecutive semesters. Once completed, SIGNALS will provide a statistically reliable laboratory to investigate massive star formation, including over 50 000 resolved H II regions: the largest, most complete, and homogeneous data base of spectroscopically and spatially resolved extragalactic H II regions ever assembled. For each field observed, three datacubes covering the spectral bands of the filters SN1 (363–386 nm), SN2 (482–513 nm), and SN3 (647–685 nm) are gathered. The spectral resolution selected for each spectral band is 1000, 1000, and 5000, respectively. As defined, the project sample will facilitate the study of small-scale nebular physics and many other phenomena linked to star formation at a mean spatial resolution of ∼20 pc. This survey also has considerable legacy value for additional topics, including planetary nebulae, diffuse ionized gas, and supernova remnants. The purpose of this paper is to present a general outlook of the survey, notably the observing strategy, galaxy sample, and science requirements
Beads-free protein immunoprecipitation for a mass spectrometry-based interactome and posttranslational modifications analysis
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