scholarly journals Effects of over-expression of TLR2 in transgenic goats on pathogen clearance and role of up-regulation of lysozyme secretion and infiltration of inflammatory cells

2012 ◽  
Vol 8 (1) ◽  
pp. 196 ◽  
Author(s):  
Shoulong Deng ◽  
Kun Yu ◽  
Baolu Zhang ◽  
Yuchang Yao ◽  
Yufeng Liu ◽  
...  
Keyword(s):  
Inflammatory Cells ◽  
Over Expression ◽  
Transgenic Goats ◽  
Pathogen Clearance

scholarly journals Responses of Mast Cells to Pathogens: Beneficial and Detrimental Roles

2021 ◽  
Vol 12 ◽  
Author(s):  
Mariela Jiménez ◽  
Daniel Cervantes-García ◽  
Laura E. Córdova-Dávalos ◽  
Marian Jesabel Pérez-Rodríguez ◽  
Claudia Gonzalez-Espinosa ◽  
...  
Keyword(s):  
Mast Cells ◽  
Current Knowledge ◽  
Inflammatory Cells ◽  
Biologically Active ◽  
Matrix Remodeling ◽  
Effector Cells ◽  
Antimicrobial Substances ◽  
Microbial Destruction ◽  
Pathogen Clearance

Mast cells (MCs) are strategically located in tissues close to the external environment, being one of the first immune cells to interact with invading pathogens. They are long living effector cells equipped with different receptors that allow microbial recognition. Once activated, MCs release numerous biologically active mediators in the site of pathogen contact, which induce vascular endothelium modification, inflammation development and extracellular matrix remodeling. Efficient and direct antimicrobial mechanisms of MCs involve phagocytosis with oxidative and non-oxidative microbial destruction, extracellular trap formation, and the release of antimicrobial substances. MCs also contribute to host defense through the attraction and activation of phagocytic and inflammatory cells, shaping the innate and adaptive immune responses. However, as part of their response to pathogens and under an impaired, sustained, or systemic activation, MCs may contribute to tissue damage. This review will focus on the current knowledge about direct and indirect contribution of MCs to pathogen clearance. Antimicrobial mechanisms of MCs are addressed with special attention to signaling pathways involved and molecular weapons implicated. The role of MCs in a dysregulated host response that can increase morbidity and mortality is also reviewed and discussed, highlighting the complexity of MCs biology in the context of host-pathogen interactions.

scholarly journals Cyclo-oxygenase 2, a putative mediator of vessel remodeling, is expressed in the brain AVM vessels and associates with inflammation

2021 ◽  
Author(s):  
Sara Keränen ◽  
Santeri Suutarinen ◽  
Rahul Mallick ◽  
Johanna P. Laakkonen ◽  
Diana Guo ◽  
...  
Keyword(s):  
Quantitative Polymerase Chain Reaction ◽  
Rank Correlation ◽  
Inflammatory Cells ◽  
Vessel Remodeling ◽  
Brain Avm ◽  
Inflammatory Drugs ◽  
Polymerase Chain ◽  
The Brain ◽  
Cox2 Expression

Abstract Background Brain arteriovenous malformations (bAVM) may rupture causing disability or death. BAVM vessels are characterized by abnormally high flow that in general triggers expansive vessel remodeling mediated by cyclo-oxygenase-2 (COX2), the target of non-steroidal anti-inflammatory drugs. We investigated whether COX2 is expressed in bAVMs and whether it associates with inflammation and haemorrhage in these lesions. Methods Tissue was obtained from surgery of 139 bAVMs and 21 normal Circle of Willis samples. The samples were studied with immunohistochemistry and real-time quantitative polymerase chain reaction (RT-PCR). Clinical data was collected from patient records. Results COX2 expression was found in 78% (109/139) of the bAVMs and localized to the vessels’ lumen or medial layer in 70% (95/135) of the bAVMs. Receptors for prostaglandin E2, a COX2-derived mediator of vascular remodeling, were found in the endothelial and smooth muscle cells and perivascular inflammatory cells of bAVMs. COX2 was expressed by infiltrating inflammatory cells and correlated with the extent of inflammation (r = .231, p = .007, Spearman rank correlation). COX2 expression did not associate with haemorrhage. Conclusion COX2 is induced in bAVMs, and possibly participates in the regulation of vessel wall remodelling and ongoing inflammation. Role of COX2 signalling in the pathobiology and clinical course of bAVMs merits further studies.

scholarly journals Chandipura virus dysregulates the expression of hsa-miR-21-5p to activate NF-κB in human microglial cells

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Neha Pandey ◽  
Meghana Rastogi ◽  
Sunit K. Singh
Keyword(s):  
Expression Pattern ◽  
Case Fatality ◽  
Microglial Cells ◽  
Luciferase Assay ◽  
Western India ◽  
Cellular Mirnas ◽  
Over Expression ◽  
Chandipura Virus ◽  
Tnf Α

Abstract Background Chandipura virus (CHPV) is a negative single-stranded RNA virus of the Rhabdoviridae family. CHPV infection has been reported in Central and Western India. CHPV causes acute encephalitis with a case fatality rate of 70 % and mostly affects children below 15 years of age. CHPV infection in brain leads to neuronal apoptosis and activation of the microglial cells. The microRNAs (miRNAs) are small endogenous non-coding RNA that regulate the gene expression. Viral infections perturb the expression pattern of cellular miRNAs, which may in turn affect the expression pattern of downstream genes. This study aims to investigate hsa-miR-21-5p mediated regulation of PTEN, AKT, NF-ĸBp65, IL-6, TNF-α, and IL-1β, in human microglial cells during CHPV infection. Methods To understand the role of hsa-miR-21-5p in CHPV infection, the human microglial cells were infected with CHPV (MOI-0.1). Real-time PCR, western blotting, Luciferase assay, over-expression and knockdown techniques were used to understand the role of hsa-miR-21-5p in the regulation of PTEN, AKT and, NF-ĸBp65, IL-6, TNF-α, and IL-1β in this study. Results The hsa-miR-21-5p was found to be upregulated during CHPV infection in human microglial cells. This led to the downregulation of PTEN which promoted the phosphorylation of AKT and NF-ĸBp65. Over-expression of hsa-miR-21-5p led to the decreased expression of PTEN and promoted further phosphorylation of AKT and NF-ĸBp65 in human microglial cells. However, the inhibition of hsa-miR-21-5p using hsa-miR-21-5p inhibitor restored the expression. Conclusions This study supports the role of hsa-miR-21-5p in the regulation of pro-inflammatory genes in CHPV infected human microglial cells.

scholarly journals Alzheimer’s Disease Pathogenesis: Role of Autophagy and Mitophagy Focusing in Microglia

2021 ◽  
Vol 22 (7) ◽  
pp. 3330
Author(s):  
Mehdi Eshraghi ◽  
Aida Adlimoghaddam ◽  
Amir Mahmoodzadeh ◽  
Farzaneh Sharifzad ◽  
Hamed Yasavoli-Sharahi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Target ◽  
Neurological Disorder ◽  
Inflammatory Cells ◽  
Disease Pathogenesis ◽  
Current Review ◽  
The Brain ◽  
Comprehensive Discussion

Alzheimer’s disease (AD) is a debilitating neurological disorder, and currently, there is no cure for it. Several pathologic alterations have been described in the brain of AD patients, but the ultimate causative mechanisms of AD are still elusive. The classic hallmarks of AD, including am-yloid plaques (Aβ) and tau tangles (tau), are the most studied features of AD. Unfortunately, all the efforts targeting these pathologies have failed to show the desired efficacy in AD patients so far. Neuroinflammation and impaired autophagy are two other main known pathologies in AD. It has been reported that these pathologies exist in AD brain long before the emergence of any clinical manifestation of AD. Microglia are the main inflammatory cells in the brain and are considered by many researchers as the next hope for finding a viable therapeutic target in AD. Interestingly, it appears that the autophagy and mitophagy are also changed in these cells in AD. Inside the cells, autophagy and inflammation interact in a bidirectional manner. In the current review, we briefly discussed an overview on autophagy and mitophagy in AD and then provided a comprehensive discussion on the role of these pathways in microglia and their involvement in AD pathogenesis.

scholarly journals The activity status of cofilin is directly related to invasion, intravasation, and metastasis of mammary tumors

2006 ◽  
Vol 173 (3) ◽  
pp. 395-404 ◽  
Author(s):  
Weigang Wang ◽  
Ghassan Mouneimne ◽  
Mazen Sidani ◽  
Jeffrey Wyckoff ◽  
Xiaoming Chen ◽  
...  
Keyword(s):  
Cell Motility ◽  
Cell Invasion ◽  
Actin Polymerization ◽  
Cancer Cell Invasion ◽  
Invasion And Metastasis ◽  
Over Expression ◽  
Cell Biol ◽  
Tumor Cell Motility ◽  
New Strategies

Understanding the mechanisms controlling cancer cell invasion and metastasis constitutes a fundamental step in setting new strategies for diagnosis, prognosis, and therapy of metastatic cancers. LIM kinase1 (LIMK1) is a member of a novel class of serine–threonine protein kinases. Cofilin, a LIMK1 substrate, is essential for the regulation of actin polymerization and depolymerization during cell migration. Previous studies have made opposite conclusions as to the role of LIMK1 in tumor cell motility and metastasis, claiming either an increase or decrease in cell motility and metastasis as a result of LIMK1 over expression (Zebda, N., O. Bernard, M. Bailly, S. Welti, D.S. Lawrence, and J.S. Condeelis. 2000. J. Cell Biol. 151:1119–1128; Davila, M., A.R. Frost, W.E. Grizzle, and R. Chakrabarti. 2003. J. Biol. Chem. 278:36868–36875; Yoshioka, K., V. Foletta, O. Bernard, and K. Itoh. 2003. Proc. Natl. Acad. Sci. USA. 100:7247–7252; Nishita, M., C. Tomizawa, M. Yamamoto, Y. Horita, K. Ohashi, and K. Mizuno. 2005. J. Cell Biol. 171:349–359). We resolve this paradox by showing that the effects of LIMK1 expression on migration, intravasation, and metastasis of cancer cells can be most simply explained by its regulation of the output of the cofilin pathway. LIMK1-mediated decreases or increases in the activity of the cofilin pathway are shown to cause proportional decreases or increases in motility, intravasation, and metastasis of tumor cells.

Over-expression of the rice OsAMT1-1 gene increases ammonium uptake and content, but impairs growth and development of plants under high ammonium nutrition

2006 ◽  
Vol 33 (2) ◽  
pp. 153 ◽  
Author(s):  
Mohammad S. Hoque ◽  
Josette Masle ◽  
Michael K. Udvardi ◽  
Peter R. Ryan ◽  
Narayana M. Upadhyaya
Keyword(s):  
Transgenic Plants ◽  
Ammonium Assimilation ◽  
Ammonium Transporter ◽  
Ammonium Uptake ◽  
Vegetative Stage ◽  
Over Expression ◽  
Transgenic Lines ◽  
Ammonium Nutrition ◽  
Maize Ubiquitin Promoter

A transgenic approach was undertaken to investigate the role of a rice ammonium transporter (OsAMT1-1) in ammonium uptake and consequent ammonium assimilation under different nitrogen regimes. Transgenic lines overexpressing OsAMT1-1 were produced by Agrobacterium-mediated transformation of two rice cultivars, Taipei 309 and Jarrah, with an OsAMT1-1 cDNA gene construct driven by the maize ubiquitin promoter. Transcript levels of OsAMT1-1 in both Taipei 309 and Jarrah transgenic lines correlated positively with transgene copy number. Shoot and root biomass of some transgenic lines decreased during seedling and early vegetative stage compared to the wild type, especially when grown under high (2 mm) ammonium nutrition. Transgenic plants, particularly those of cv. Jarrah recovered in the mid-vegetative stage under high ammonium nutrition. Roots of the transgenic plants showed increased ammonium uptake and ammonium content. We conclude that the decreased biomass of the transgenic lines at early stages of growth might be caused by the accumulation of ammonium in the roots owing to the inability of ammonium assimilation to match the greater ammonium uptake.

Abstract 207: Unc-51-like Kinase 1 (ULK1) Plays A Crucial Role In Mitophagy In Cardiomyocytes

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Toshiro Saito ◽  
Junichi Sadoshima
Keyword(s):  
Glucose Deprivation ◽  
High Ratio ◽  
Control Mechanisms ◽  
Oxygen Species ◽  
Predominant Role ◽  
Mitochondrial Quality Control ◽  
Over Expression ◽  
Pathological Conditions

The mitochondrion is an essential organelle that supplies ATP in cardiomyocytes (CMs). However, damaged mitochondria are harmful via the production of reactive oxygen species and induction of apoptosis in pathological conditions. Therefore, quality of mitochondria should be controlled tightly through various mitochondrial quality control mechanisms. Mitochondrial autophagy (mitophagy) is considered an integral part of this mechanism, and recent investigations uncovered the role of PINK1 and Parkin in mitophagy. However, these observations were made under artificial conditions, such as over-expression of Parkin or treatment with CCCP, and thus the precise mechanism has not been fully elucidated in more pathophysiologically relevant conditions. Recent evidence suggests that mitophagy can take place independently of ATG7, a molecule essential for the conventional form of autophagy, and that this form of autophagy is ULK1-dependent. We investigated the role of ULK1 and ATG7 in mediating mitophagy using mitochondria-targeted Keima (Mito-Keima) in cultured rat neonatal CMs. Keima has a bimodal excitation spectrum peaking at 440 and 560 nm, corresponding to the neutral and acidic pH, respectively. In CMs transfected with Mito-Keima, the fluorescent dots with a high 560nm/440nm ratio represent the mitochondria incorporated into autolysosomes which indicate mitophagy. Here we report that ULK1 plays a more predominant role in glucose deprivation (GD) -induced mitophagy than ATG7. Control CMs exhibited 8.7±1.0 % of the area of high-ratio dots per cells after GD. Knockdown of ULK1 significantly reduced the area to 2.3±0.9 % in CMs after GD (p<0.01, vs sh-Control). The reduction was significantly greater in CMs with knockdown of ULK1 than that of ATG7 (7.0±1.6 %, p<0.05, sh-ULK1 vs sh-ATG7). In addition, knockdown of Beclin1 and Drp1 also significantly decreased the area of high-ratio dots (about 1.0 % and 0.5 %, respectively). Overexpression of ULK1 was sufficient to induce mitophagy without starvation, whereas that of ATG7 was not. These results suggest that ULK1, Beclin1 and Drp1 play an essential role in mediating GD-induced mitophagy in CMs.

Truth and Privilege

2021 ◽  
Author(s):  
Lyndsay Campbell
Keyword(s):  
Nova Scotia ◽  
Social History ◽  
American Revolution ◽  
Institutional Design ◽  
Freedom Of Expression ◽  
Over Expression ◽  
Essential Question ◽  
The Press ◽  
The Common

Truth and Privilege is a comparative study that brings together legal, constitutional and social history to explore the common law's diverging paths in two kindred places committed to freedom of expression but separated by the American Revolution. Comparing Nova Scotia and Massachusetts, Lyndsay Campbell examines the development of libel law, the defences of truth and privilege, and the place of courts as fora for disputes. She contrasts courts' centrality in struggles over expression and the interpretation of individual rights in Massachusetts with concerns about defining protective boundaries for the press and individuals through institutional design in Nova Scotia. Campbell's rich analysis acts as a lens through which to understand the role of law in shaping societal change in the nineteenth century, shedding light on the essential question we still grapple with today: what should law's role be in regulating expression we perceive as harmful?

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