Endotoxin Triggers Tumor Initiation Events in Nontumorigenic Breast Epithelial Cells and Enhances Invasion-Related Phenotype in Pretumorigenic and Tumorigenic Breast Epithelial CellsRead the full article
International Journal of Inflammation publishes papers on the molecular basis, cell biology and pharmacology of inflammation, including acute/chronic inflammation and the cellular processes/molecular mechanisms involved in inflammatory responses.
International Journal of Inflammation maintains an Editorial Board of practicing researchers from around the world, to ensure manuscripts are handled by editors who are experts in the field of study.
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Influence of Pathogen Type on Neonatal Sepsis Biomarkers
Understanding immunoregulation in newborns can help to determine the pathophysiology of neonatal sepsis and will contribute to improve the diagnosis, prognosis, and treatment and remains an urgent and unmet medical need to understand hyperinflammation or hypoinflammation associated with sepsis in newborns. This study included infants (up to 4 days old). The “sepsis” criteria was a positive blood culture. C-reactive protein demonstrates a strong dependence on the pathogen etiology. Therefore, its diagnostic odds ratio in Gram-positive bacteremia was 2.7 and the sensitivity was 45%, while Gram-negative was 15.0 and 81.8%, respectively. A neutrophil-lymphocyte ratio above 1 and thrombocytopenia below 109 cells/L generally do not depend on the type of pathogen and have a specificity of 95%; however, the sensitivity of these markers is low. nCD64 demonstrated good analytical performance and was equally discriminated in both Gram (+) and Gram (−) cultures. The sensitivity was 87.5–89%, and the specificity was 65%. The HLA-DR and programmed cell death protein study found that activation-deactivation processes in systemic infection is different at points of application depending on the type of pathogen: Gram-positive infections showed various ways of activation of monocytes (by reducing suppressive signals) and lymphocytes (an increase in activation signals), and Gram-negative pathogens were most commonly involved in suppressing monocytic activation. Thus, the difference in the bacteremia model can partially explain the problems with the high variability of immunologic markers in neonatal sepsis.
Osteoarthritis Affects Mammalian Oogenesis: Effects of Collagenase-Induced Osteoarthritis on Oocyte Cytoskeleton in a Mouse Model
Known as a degenerative joint disorder of advanced age affecting predominantly females, osteoarthritis can develop in younger and actively working people because of activities involving loading and injuries of joints. Collagenase-induced osteoarthritis (CIOA) in a mouse model allowed us to investigate for the first time its effects on key cytoskeletal structures (meiotic spindles and actin distribution) of ovulated mouse oocytes. Their meiotic spindles, actin caps, and chromatin were analyzed by immunofluorescence. A total of 193 oocytes from mice with CIOA and 209 from control animals were obtained, almost all in metaphase I (M I) or metaphase II (MII). The maturation rate was lower in CIOA (26.42% M II) than in controls (55.50% M II). CIOA oocytes had significantly larger spindles (average 37 μm versus 25 μm in controls, ), with a proportion of large spindles more than 64% in CIOA versus up to 15% in controls (). Meiotic spindles were wider in 68.35% M I and 54.90% M II of CIOA oocytes (mean 18.04 μm M I and 17.34 μm M II versus controls: 11.64 μm M I and 12.64 μm M II), and their poles were approximately two times broader (mean 6.9 μm) in CIOA than in controls (3.6 μm). CIOA oocytes often contained disoriented microtubules. Actin cap was visible in over 91% of controls and less than 20% of CIOA oocytes. Many CIOA oocytes without an actin cap had a nonpolarized thick peripheral actin ring (61.87% of M I and 52.94% of M II). Chromosome alignment was normal in more than 82% in both groups. In conclusion, CIOA affects the cytoskeleton of ovulated mouse oocytes—meiotic spindles are longer and wider, their poles are broader and with disorganized fibers, and the actin cap is replaced by a broad nonpolarized ring. Nevertheless, meiotic spindles were successfully formed in CIOA oocytes and, even when abnormal, allowed correct alignment of chromosomes.
Idiopathic Pulmonary Comorbidities and Mechanisms
Idiopathic pulmonary fibrosis (IPF) is a disease with an unknown etiology mainly characterized by a progressive decline of lung function due to the scarring of the tissue deep in the lungs. The overall survival after diagnosis remains low between 3 and 5 years. IPF is a heterogeneous disease and much progress has been made in the past decade in understanding the disease mechanisms that contributed to the development of two new drugs, pirfenidone and nintedanib, which improved the therapeutic management of the disease. The understanding of the cofactors and comorbidities of IPF also contributed to improved management of the disease outcome. In the present review, we evaluate scientific evidence which indicates IPF as a risk factor for other diseases based on the complexity of molecular and cellular mechanisms involved in the disease development and of comorbidities. We conclude from the existing literature that while much progress has been made in understating the mechanisms involved in IPF development, further studies are still necessary to fully understand IPF pathogenesis which will contribute to the identification of novel therapeutic targets for IPF management as well as other diseases for which IPF is a major risk factor.
Increased Levels of CD107a and Intracellular Cytokines in IL-2 Stimulated PBMCs from Endometriosis Patients
It has been postulated that the immune system is impaired in individuals with endometriosis, with attention directed to natural killer (NK) cells. Specifically, it has been hypothesized that altered numbers of peripheral NK cells in blood are associated with the presence of endometriotic lesions. This study aimed to evaluate the level of the peripheral NK cell surface marker CD107a in endometriosis in the presence of IL-2 stimulation. Peripheral blood mononuclear cells (PBMCs) were obtained from 7 women with endometriosis and 7 women without endometriosis. The PBMCs were divided into two groups and either treated with recombinant IL-2 or left untreated. The cytotoxic activity of the PBMCs toward target cells (K562) was evaluated. Then, both groups were cocultured for 4 days. The expressions of CD107a, TNF-α, and IFN-γ were determined using flow cytometry analysis. There was no difference in the expression of CD107a prior to IL-2 stimulation in PBMCs from women with endometriosis compared to those from women without endometriosis. However, we observed upregulation of the expression of the surface marker CD107a after treatment in the endometriosis group. In addition, there was a significant difference in CD107a expression in the endometriosis group before versus after stimulation with IL-2 ( < 0.01). We also found no difference in the production of TNF-α and IFN-γ before versus after treatment with IL-2 in either groups. The levels of CD107a were significantly enhanced in peripheral blood taken from women with endometriosis after treatment with IL-2.
Xanthine Oxidase-Induced Inflammatory Responses in Respiratory Epithelial Cells: A Review in Immunopathology of COVID-19
Xanthine oxidase (XO) is an enzyme that catalyzes the production of uric acid and superoxide radicals from purine bases: hypoxanthine and xanthine and is also expressed in respiratory epithelial cells. Uric acid, which is also considered a danger associated molecule pattern (DAMP), could trigger a series of inflammatory responses by activating the inflammasome complex path and NF-κB within the endothelial cells and by inducing proinflammatory cytokine release. Concurrently, XO also converts the superoxide radicals into hydroxyl radicals that further induce inflammatory responses. These conditions will ultimately sum up a hyperinflammation condition commonly dubbed as cytokine storm syndrome (CSS). The expression of proinflammatory cytokines and neutrophil chemokines may be reduced by XO inhibitor, as observed in human respiratory syncytial virus (HRSV)-infected A549 cells. Our review emphasizes that XO may have an essential role as an anti-inflammation therapy for respiratory viral infection, including coronavirus disease 2019 (COVID-19).
Phase I/II Clinical Trial of Autologous Activated Platelet-Rich Plasma (aaPRP) in the Treatment of Severe Coronavirus Disease 2019 (COVID-19) Patients
Background. The outbreak of Coronavirus Disease 2019 (COVID-19) has been increasing rapidly. This disease causes an increase in proinflammatory cytokine production that leads to cytokine storm or cytokine release syndrome (CRS). Autologous activated platelet-rich plasma (aaPRP) contains various types of growth factors and anti-inflammatory cytokines that may have the potential to suppress CRS. This study of phase I/II trial was aimed to evaluate the safety and efficacy of aaPRP to treat severe COVID-19 patients. Methods. A total of 10 severe COVID-19 patients from Koja Regional Public Hospital (Koja RPH) were admitted to the intensive care unit (ICU). All patients received aaPRP administration three times. Primary outcomes involving the duration of hospitalization, oxygen needs, time of recovery, and mortality were observed. Secondary outcomes involving C-reactive protein (CRP), neutrophil, lymphocyte, and lymphocyte-to-CRP (LCR) and neutrophil-lymphocyte ratio (NLR) were analyzed. Results. All patients were transferred to the ICU with a median duration of 9 days. All patients received oxygen at enrollment and nine of ten patients recovered from the ICU and transferred to the ward room. There was one patient who passed away in the ICU due to heart failure. The results of secondary outcomes showed that CRP value and lymphocytes counts were significantly decreased while neutrophils, LCR, and NLR were slightly increased after aaPRP administration. Conclusions. Our results of the phase I/II trial demonstrated that the use of aaPRP in severe COVID-19 patients was safe and not associated with serious adverse events, which showed that aaPRP was a promising adjunctive therapy for severe COVID-19 patients.