scholarly journals The Biological Properties of the Strain Francisella tularensis 15 NIIEG with Decreased Gene Expression sodB, Encoding Fe-Dependent Superoxide Dismutase

2016 ◽  
Vol 15 (5) ◽  
pp. 24-29
Author(s):  
M. A. Sotnikova ◽  
T. B. Kravchenko ◽  
I. V. Bakhteeva ◽  
R. I. Mironova ◽  
T. I. Kombarova ◽  
...  

Relevance. Superoxide anion has bactericidal properties and is also an important inducer of proinflammatory cytokines in macrophages. We have created F. tularensis 15/sodBII strain with transiently decreased FeSOD synthesis level and more sensitive to oxidative stress. So we suggest that the modified vaccine strain have lower reactogenicity. Goal. Studying of effect of sodB gene expression modulation on biological properties of vaccine F. tularensis strain 15 NIIEG. Materials and methods. F. tularensis survival in macrophage-like cell line J774.1A and in spleen and liver of infected mice were analyzed through colony-forming unit enumeration. Strains reactogenicity was assessed by the dynamics of change in weight of infected mice. Efficacy of immune response generated by mutant strain of F. tularensis 15/sodBII was estimated with virulent F. tularensis strain Schu S4 infection in the BALB/c mice model. Results. Degree of protection was significantly more pronounced in the mice vaccinated with the strain F. tularensis with decreased sodB gene expression in comparison with parental F. tularensis strain NIIEG 15. Conclusions. The modified strain of F. tularensis 15/sodBII may be consider as a promising variant for development of a new tularemia vaccine with reduced reactogenicity.

Vaccines ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 4 ◽  
Author(s):  
Muktha S. Natrajan ◽  
Nadine Rouphael ◽  
Lilin Lai ◽  
Dmitri Kazmin ◽  
Travis L. Jensen ◽  
...  

Background: Tularemia is a potential biological weapon due to its high infectivity and ease of dissemination. This study aimed to characterize the innate and adaptive responses induced by two different lots of a live attenuated tularemia vaccine and compare them to other well-characterized viral vaccine immune responses. Methods: Microarray analyses were performed on human peripheral blood mononuclear cells (PBMCs) to determine changes in transcriptional activity that correlated with changes detected by cellular phenotyping, cytokine signaling, and serological assays. Transcriptional profiles after tularemia vaccination were compared with yellow fever [YF-17D], inactivated [TIV], and live attenuated [LAIV] influenza. Results: Tularemia vaccine lots produced strong innate immune responses by Day 2 after vaccination, with an increase in monocytes, NK cells, and cytokine signaling. T cell responses peaked at Day 14. Changes in gene expression, including upregulation of STAT1, GBP1, and IFIT2, predicted tularemia-specific antibody responses. Changes in CCL20 expression positively correlated with peak CD8+ T cell responses, but negatively correlated with peak CD4+ T cell activation. Tularemia vaccines elicited gene expression signatures similar to other replicating vaccines, inducing early upregulation of interferon-inducible genes. Conclusions: A systems vaccinology approach identified that tularemia vaccines induce a strong innate immune response early after vaccination, similar to the response seen after well-studied viral vaccines, and produce unique transcriptional signatures that are strongly correlated to the induction of T cell and antibody responses.


Virology ◽  
1990 ◽  
Vol 177 (1) ◽  
pp. 380-383 ◽  
Author(s):  
V.S. Kalyanaraman ◽  
V. Rodriguez ◽  
S. Josephs ◽  
R.C. Gallo ◽  
M.G. Sarngadharan

2010 ◽  
Author(s):  
Reamin Chu ◽  
Hang‐Rong Lei ◽  
Cheng‐Se Lin ◽  
Cheng‐Se Lin ◽  
Chien‐Yueh Lee ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2780
Author(s):  
Atsushi Tanabe ◽  
Hiroeki Sahara

Numerous findings have indicated that CSCs, which are present at a low frequency inside primary tumors, are the main cause of therapy resistance and cancer recurrence. Although various therapeutic methods targeting CSCs have been attempted for eliminating cancer cells completely, the complicated characteristics of CSCs have hampered such attempts. In analyzing the biological properties of CSCs, it was revealed that CSCs have a peculiar metabolism that is distinct from non-CSCs to maintain their stemness properties. The CSC metabolism involves not only the catabolic and anabolic pathways, but also intracellular signaling, gene expression, and redox balance. In addition, CSCs can reprogram their metabolism to flexibly respond to environmental changes. In this review, we focus on the flexible metabolic mechanisms of CSCs, and highlight the new therapeutics that target CSC metabolism.


2013 ◽  
Vol 14 (4) ◽  
pp. S45
Author(s):  
C. Monteiro ◽  
M. Matos ◽  
D. Lima ◽  
V. Galhardo

2021 ◽  
Vol 8 ◽  
Author(s):  
Zheng Wang ◽  
Yanchen Zhao ◽  
Yan Jiang ◽  
Weihua Chu

In this study, an extracellular acidic polysaccharide (EAPS) from marine Rhodotorula sp. RY1801 was extracted, and its biological properties were investigated. EAPS is mainly composed of monosaccharides, including mannose, rhamnose, glucose, galactose, and fucose, had an average molecular weight of 5.902 × 107 Da. The results indicated that EAPS can promote the growth of Lactobacillus acidophilus and L. acidophilus plantarum. EAPS is capable of scavenging both superoxide anion and hydroxyl radicals in vitro. The highest scavenging rate of superoxide anion and hydroxyl radicals is 29 and 84%, respectively. Using in vivo model, we found that the EAPS can expand the lifespan and increase the disease resistance of Caenorhabditis elegans against Klebsiella pneumoniae infection via the DAF-2/DAF-16 pathway. These results suggested that EAPS from marine Rhodotorula sp. RY1801 could promote the growth of beneficial bacteria and can be used as an antioxidant and immunomodulator, which had considerable potential in the food and health industry.


2020 ◽  
Author(s):  
So Yeong Cheon ◽  
Bon-Nyeo Koo ◽  
So Yeon Kim ◽  
Eun Hee Kam ◽  
Junhyun Nam ◽  
...  

Abstract BackgroundPostoperative delirium is a common neuropsychiatric syndrome resulting in a high postsurgical mortality rate and decline in postdischarge function. Extensive research has been performed on both human and animal delirium models due to their clinical significance, focusing on systemic inflammation and consequent neuroinflammation playing a key in the pathogenesis of postoperative cognitive dysfunctions. Since animal models are widely utilized for pathophysiological study of neuropsychiatric disorders, this study aimed at examining the validity of the scopolamine-induced delirium mice model with respect to the neuroinflammatory hypothesis of delirium. MethodsMale C57BL/6 mice were treated with intraperitoneal scopolamine (2 mg/kg). Neurobehavioural tests were performed to evaluate the changes in cognitive functions, including learning and memory, and the level of anxiety after surgery or scopolamine treatment. The levels of pro-inflammatory cytokines (IL-1ꞵ, IL-18, and TNF-α) and inflammasome components (NLRP3, ASC, and caspase-1) in different brain regions were measured. Gene expression profiles were also examined using whole-genome RNA sequencing analyses to compare gene expression patterns of different mice models.Results Scopolamine treatment showed significant increase in the level of anxiety and impairments in memory and cognitive function associated with increased level of pro-inflammatory cytokines and NLRP3 inflammasome components. Genetic analysis confirmed the different expression patterns of the genes involved in immune response and inflammation and those related with the development of the nervous system in both surgery and scopolamine-induced mice models. Conclusions The scopolamine-induced delirium mice model successfully showed that analogous neuropsychiatric changes coincide with the neuroinflammatory hypothesis for pathogenesis of delirium.


Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3308
Author(s):  
Irina Zarafu ◽  
Lilia Matei ◽  
Coralia Bleotu ◽  
Petre Ionita ◽  
Arnaud Tatibouët ◽  
...  

Starting from isoniazid and carboxylic acids as precursors, thirteen new hydrazides and 1,3,4-oxadiazoles of 2-(4-substituted-phenoxymethyl)-benzoic acids were synthesized and characterized by appropriate means. Their biological properties were evaluated in terms of apoptosis, cell cycle blocking, and drug metabolism gene expression on HCT-8 and HT-29 cell lines. In vitro antimicrobial tests were performed by the microplate Alamar Blue assay for the anti-mycobacterial activities and an adapted agar disk diffusion technique for other non-tubercular bacterial strains. The best antibacterial activity (anti-Mycobacterium tuberculosis effects) was proved by 9. Compounds 7, 8, and 9 determined blocking of G1 phase. Compound 7 proved to be toxic, inducing apoptosis in 54% of cells after 72 h, an effect that can be predicted by the increased expression of mRNA caspases 3 and 7 after 24 h. The influence of compounds on gene expression of enzymes implicated in drug metabolism indicates that synthesized compounds could be metabolized via other pathways than NAT2, spanning adverse effects of isoniazid. Compound 9 had the best antibacterial activity, being used as a disinfectant agent. Compounds 7, 8, and 9, seemed to have antitumor potential. Further studies on the action mechanism of these compounds on the cell cycle may bring new information regarding their biological activity.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6055-6055
Author(s):  
Haitham Mirghani ◽  
Catherine Ory ◽  
Nicolas Ugolin ◽  
Furrat Amen ◽  
Joel Guigay ◽  
...  

6055 Background: Strong evidence supports the hypothesis that high-risk human papillomavirus (HPV), particularly HPV16, is a causative agent for an increasing subset of oropharyngeal squamous cell carcinomas (OPSCC). These tumors have distinct oncogenic mechanisms and a more favorable prognosis than tobacco induced OPSCC. Although these differences emphasize the need for a specific therapeutic approach, HPV status is still not used to guide treatment. A better understanding of the molecular profile related to HPV16 induced OPSCC may help to develop personalized treatments. Methods: To identify an HPV16-related molecular signature, we compared the gene expression profile of 15 transcriptionally active HPV16-positive and 15 HPV16-negative OPSCC. The study was conducted in two steps. First, a learning set of 16 OPSCC comprising 8 HPV16-positives and 8 HPV16-negatives OPSCC was analyzed in order to identify the signature. Potentially confounding factors of stage, sex and tobacco consumption were equally distributed in both groups. Secondarily, the robustness of this signature was further confirmed by blind case-by-case classification of an independent set of 14 OPSCC. Results: We identified a signature composed of 224 genes which discriminates HPV16-induced OPSCC from their tobacco induced counterparts. After the viral status was revealed, 13 out of 14 tumors were correctly classified according to tumor etiology, 1/14 was undetermined and none were misclassified. Interestingly, deregulated genes in HPV16-positive tumors are principally involved in innate immunity, in cell cycle regulation through the TP53/RB/E2F pathway, and autophagy through mTOR regulation. Well known targets of E6 and E7 proteins are also found to be deregulated. Conclusions: Our results demonstrate that a set of selected genes can distinguish OPSCC according to etiology. These genes shed light on HPV16 induced carcinogenesis since specific molecular pathways are deregulated. Further investigations are required for a better understanding of the differing natural histories and biological properties of these tumors. These properties may be exploited as a target of novel therapeutic agents in HPV-related OPSCC.


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