Staphylococcus aureus (S. aureus) internalization into bovine mammary epithelial cells (bMECs) is considered an important pathogenic mechanism for the establishment of mastitis. Given the interesting ...link between selenium (Se) status and mastitis, our objective was to prove that Se was essential to suppress pro-inflammatory mediators, in part, by modulation of Toll-like receptor2 (TLR2), nuclear factor kappaB (NF-κB) and mitogen activated protein kinase (MAPK) signal transduction pathway in bMECs.
Results showed that Se (0~ 16 μM) did not affect the growth of bMECs. The mRNA expression of TLR2, Myeloid differentiation factor 88 (Myd88), Interleukin-1 receptor-associated kinase4 (Irak4), Interleukin-1 receptor-associated kinase1 (Irak1) and TNF receptor-associated factor6 (Traf6) in TLR2 signal pathway were increased or significantly increased by S. aureus. Se played an important role in regulating the genes expression of TLR2, Myd88, Traf6 but not in controlling the expression of Irak4 and Irak1. In addition, Se exerted strong inhibitory effects on the genes expression of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) induced by S. aureus. To further investigate the possible signaling mechanisms involved in the processes, we analyzed the role of MAPK and NF-κB signaling pathway in inflammation response in S. aureus-stimulated bMECs in vitro. Results showed that the phosphorylation of inhibitory kappaB alpha (IκBα), p65, p38 and extracellular regulated protein kinase (Erk) were significantly increased in S. aureus-stimulated bMECs. It indicated that S. aureus activated NF-κB and MAPK signaling pathway. We also examined the effects of Se on the phosphorylation of IκBα, p65, p38 and Erk in NF-κB and MAPK signaling pathway, which have well been proved to control the synthesis and release of pro-inflammatory mediators during inflammation. The findings are exciting, that pretreatment with Se (4, 8 μM) significantly suppressed the phosphorylation of IκBα, p65, p38 and Erk.
These results suggest that Se down-regulates inflammatory mediators TNF-α, IL-1β and IL-6 gene expressions via TLR2, NF-κB and MAPK signaling pathway in S. aureus-stimulated bMECs, which may be responsible for the anti-inflammatory effect of Se.
Fallgirls provides an analysis of the abuses that took place at Abu Ghraib in terms of social theory, gender and power, based on first-hand participant-observations of the courts-martials of Lynndie ...England and Sabrina Harman. This book examines the trials themselves, including interactions with soldiers and defense teams, documents pertaining to the courts-martials, US government reports and photographs from Abu Ghraib, in order to challenge the view that the abuses were carried out at the hands of a few rogue soldiers. With a keen focus on gender and sexuality as prominent aspects of the abuses themselves, as well as the ways in which they were portrayed and tried, Fallgirls engages with modern feminist thought and contemporary social theory in order to analyse the manner in which the abuses were framed, whilst also exploring the various lived realities of Abu Ghraib by both prisoners and soldiers alike.
In response to the incidence of oculofacial traumas that were observed during the wars in Iraq and Afghanistan, military medical care provider training programs have placed an increased focus on the ...treatment of ocular traumas. As such, the Lateral Canthotomy and Cantholysis (LCC) Training System was developed to simulate the anatomy of the human eye and to mimic the symptoms of an eye that is afflicted with a retrobulbar hemorrhage. We report a mixed-methods psychophysics study that was conducted during the development of the LCC Training System to determine the appropriate retrobulbar pressure to be simulated by the trainer to provide anatomically accurate sensations of pressure. More than 200 eye inserts with either pre-or post-LCC pressures were evaluated by oculofacial trauma subject matter experts. The captured evaluations enabled the research team to identify and specify the pressure requirements that would be used by manufacturers to produce an anatomically and tactically-accurate trainer.
Abstract
In the current study, uranium concentrations were measured in tap water samples collected from selected regions in Muthanna governorate southern Iraq. Fission track analysis technique with ...alpha track detector (CR-39) has been applied to determine the uranium content. The results of this experimental investigation showed that the highest value of uranium concentration in tap water samples was 4.05 ± 0.16 μg/l found in Al-Hassan district, while the lowest value was 2.02 ± 0.13 μg/l found in Al-Mualimin district. The average value of uranium content in tap water samples was 3.01 ± 0.15 μg/l. The results of the uranium content were compared with the published data and they were found to be within the safety levels.
Von Marokko bis Bahrain: Die Jahre 2010 und 2011 markieren bis heute eine gesellschaftspolitische Zäsur in Nordafrika und im Nahen Osten. Mit unglaublichem Mut erhoben sich Millionen Menschen gegen ...Herrschende, deren Macht innenpolitisch auf brutaler Repression und außenpolitisch auf einer fatalen Mischung aus westlichen Interessen, Gleichgültigkeit und Kurzsichtigkeit beruhte. Das Besondere an diesen Aufständen aber ist, dass nicht sozioökonomische Forderungen im Mittelpunkt standen, sondern etwas, das geistiger scheint und existentieller ist: Würde. Vieles von dem, was die Protestierenden anstrebten, hat sich nicht erfüllt. Doch zeichnet sich in den Auseinandersetzungen der Beiträger*innen dieses Bandes mit dem, was sie erlebt und erreicht haben, ab, was trotz allem aus den Revolutionen gewachsen ist: Räume für Debatten, die vorher undenkbar waren, und die Möglichkeit, erstmals in einer Zukunft zu schwelgen, die sie repräsentiert.
Influenza A virus (IAV) is the most common infectious agent in humans, and infects approximately 10-20% of the world's population, resulting in 3-5 million hospitalizations per year. A scientific ...literature search was performed using the PubMed database and the Medical Subject Headings (MeSH) "Influenza A H1N1" and "Genetic susceptibility". Due to the amount of information and evidence about genetic susceptibility generated from the studies carried out in the last influenza A H1N1 pandemic, studies published between January 2009 to May 2020 were considered; 119 papers were found. Several pathways are involved in the host defense against IAV infection (innate immune response, pro-inflammatory cytokines, chemokines, complement activation, and HLA molecules participating in viral antigen presentation). On the other hand, single nucleotide polymorphisms (SNPs) are a type of variation involving the change of a single base pair that can mean that encoded proteins do not carry out their functions properly, allowing higher viral replication and abnormal host response to infection, such as a cytokine storm. Some of the most studied SNPs associated with IAV infection genetic susceptibility are located in the
,
,
, and
genes, affecting host immune responses through abnormal complement activation. Also, SNPs in
(which participates in endosomes and lysosomes fusion) represent some of the most critical polymorphisms associated with IAV infection, suggesting an ineffective virus clearance. Regarding inflammatory response genes, single nucleotide variants in
,
,
,
,
,
,
, and HLA complex are associated with altered phenotype in pro-inflammatory molecules, participating in IAV infection and the severest form of the disease.
Von Marokko bis Bahrain: Die Jahre 2010 und 2011 markieren bis heute eine gesellschaftspolitische Zäsur in Nordafrika und im Nahen Osten. Mit unglaublichem Mut erhoben sich Millionen Menschen gegen ...Herrschende, deren Macht innenpolitisch auf brutaler Repression und außenpolitisch auf einer fatalen Mischung aus westlichen Interessen, Gleichgültigkeit und Kurzsichtigkeit beruhte. Das Besondere an diesen Aufständen aber ist, dass nicht sozioökonomische Forderungen im Mittelpunkt standen, sondern etwas, das geistiger scheint und existentieller ist: Würde. Vieles von dem, was die Protestierenden anstrebten, hat sich nicht erfüllt. Doch zeichnet sich in den Auseinandersetzungen der Beiträger*innen dieses Bandes mit dem, was sie erlebt und erreicht haben, ab, was trotz allem aus den Revolutionen gewachsen ist: Räume für Debatten, die vorher undenkbar waren, und die Möglichkeit, erstmals in einer Zukunft zu schwelgen, die sie repräsentiert.
Interleukin-1receptor-associated kinase 1 (IRAK1) plays a critical role in systemic lupus erythematosus (SLE). It was reported that SLE was associated with an inflammatory response mediated by ...defective immune tolerance, including overproduction of autoantibodies, chronic inflammation, and organ damage. Previous reports stated paeoniflorin (PF) had an immunosuppressive effect. The purpose of this study was to determine the anti-inflammatory effect of PF in SLE and its underlying mechanisms. Followed by induced with lipopolysaccharide (LPS), the splenocytes and the isolated CD4+ T lymphocytes of MRL/lpr mice were divided into three groups: control group, LPS group, and LPS + PF group, respectively. MRL/MP mice were used as the control group (treated with distilled water). The MRL/lpr mice were randomly divided into three groups: the model group (treated with distilled water), the prednisone group, and the PF group. The MRL/lpr mice were treated with prednisone acetate (5 mg/kg) and PF (25, 50, and 75 mg/kg) for eight weeks. Subsequently, ELISA, qRT-PCR, western blotting, HE, and Masson staining were performed to detect various indicators. The results of Cell Counting Kit-8 (CCK-8) showed that 10 μg/mL of LPS had the optimum effect on cell viability, and 50 μmol/L of PF had no obvious cytotoxicity to LPS-treated cells. PF reduced the expression level of IRAK1-nuclearfactor-κB (NF-κB) and its downstream inflammatory cytokines in the splenocytes and CD4+ T lymphocytes of MRL/lpr mice stimulated by LPS, especially in the latter. The serum antibody contents in the PF group mice were reduced, and the kidney damage was also alleviated accordingly. Moreover, the IRAK1/inhibitor of the nuclear factor-κB kinase (IKK)/NF-κB inhibitor (IκB)/NF-κB pathways was found to be involved in the anti-inflammation effect of PF in the kidney and spleen. In conclusion, it is thought that PF may have the potential to be used as a therapeutic agent to reduce the inflammatory activity of SLE. Inhibition of the IRAK1-NF-κB pathway may help formulate novel therapeutic tactics for SLE.
Cellular heterogeneity and immune cell molecular phenotypes may be involved in the malignant progression of glioblastoma (GBM). In this study, we aimed to know whether the heterogeneity of ...tumour-associated macrophages contributes to the recurrence and outcomes of glioblastoma patients. Single-cell RNA sequencing (scRNA-Seq) data were used to assess the heterogeneity of CD45 + immune cells in recurrent GBM and analyse differentially expressed genes (DEGs) in master cells. Then, a prognostic signature based on the identified DEGs was established and validated, the correlation between risk score and tumour microenvironment (TME) was explored. The correlation between immune infiltration and
LGMN
, an important DEG in GBM tumour-associated macrophages (TAMs) was illuminated, using integrated bioinformatics analyses. Finally, immunohistochemistry and multiplex immunohistochemistry (mIHC) were used to analyse the expression of
LGMN
in GBM tissues from our hospital. scRNA-Seq analysis showed that the heterogeneity of recurrent GBM mainly comes from TAMs, which can be divided into 8 cell subclusters. Among these subclusters, TAM1 (markers: CXCL10, ADORA3), TAM3 (markers: MRC1, CFP), TAM4 (markers: GPNMB, PLTP), and TAM5 (markers: CCL4, IRAK2) were specifically present in recurrent GBM. After 342 DEGs in TAMs were identified, a prognostic signature was established based on 13 TAM-associated DEGs, and this signature could serve as an excellent prognostic predictor for patients with GBM.
LGMN
, one of 13 TAM-associated DEGs, was an important gene in lysosome pathway, we found that macrophage infiltration levels were higher after
LGMN
upregulation. GBM tissues from our hospital were collected for histopathologic validation, then
LGMN
was co-expressed with CD68, which is associated with the immune regulation of GBM. In conclusion, cell heterogeneity of TAMs is important for recurrent GBM, a prognostic signature based on 13 TAM-related DEGs can predict the survival outcome of GBM patients. An important DEG,
LGMN
may regulate the immune cell infiltration of GBM.
To explore the mechanisms of ovarian aging, we performed overall analysis on the age-related alterations of gene expression profiles in mouse germinal vesicle (GV) stage oocytes by means of ...single-cell RNA-sequencing method (scRNA-seq).
Two age groups (5-week-old and 32-week-old) female KM mice were used as young and old models. Subsequently, GV oocytes were collected for scRNA-seq. The bioinformatics was performed to analyze and compare the differences of gene expression profile between GV oocytes of young and old mice.
The analysis of scRNA-seq data showed that there were 624 differential expressed genes (DEGs) between two age groups of mouse GV stage oocytes. Four hundred forty-nine DEGs were up-regulated while 175 DEGs were down-regulated in the GV oocytes of the old group. KEGG pathway analysis revealed that the genes involved in mitochondrial function including oxidative phosphorylation and ATP production pathway were significantly down-regulated in GV oocytes of 32-week-old mice, especially the mitochondrial encoded NADH dehydrogenase (mt-Nd), including mt-Nd2, mt-Nd3, mt-Nd4, mt-Nd4L and mt-Nd5. Analysis of DEGs revealed that endoplasmic reticulum stress-related genes including AdipoR2, IRAK-1, RCAN1 and MsrB1 were significantly down-regulated in GV oocytes of 32-week-old mice. Also, analysis of DEGs demonstrated that anti-oxidation-related genes including Erbb3、Rcan1、Gsto2 and Msrb1 were significantly down-regulated in GV oocytes of old group.
The disorder of mitochondrial function, endoplasmic reticulum stress and the reduced antioxidant capability might be involved in the progression of oocyte aging. Especially, the down regulation of mitochondrial encoded subunits of respiratory chain complexes might play critical roles in the relevant mechanisms.
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