Mechanism Of Inflammatory Reaction Research Articles

Research Progress of Duodenal-Jejunal Bypass Liner in the Treatment of Obesity and Type 2 Diabetes Mellitus.

With the development of economy and improvement of people's living standards, the incidence of obesity and type 2 diabetes mellitus (T2DM) has increased significantly and obesity has also become one of the most important risk factors of T2DM. In light of these trends, there have been many ways to take effect in losing weight. However, they also have corresponding deficiencies including inapparent curative effect, complex and incomplete reversible procedures and severe complications. Duodenal-Jejunal Bypass Liner (DJBL), which mimics Roux-en-Y gastric bypass (RYGB), is proved to play a key role in weight loss and control of T2DM. DJBL is reversible, less invasive and is more suitable for the treatment of obesity and T2DM, which is associated with multiple mechanisms, including incretin effect, gastric emptying mechanism, bile acid regulation, intestinal microbiota, inflammatory reaction mechanism and neural mechanism. In our review, we aimed to elaborate DJBL's clinical efficacy, safety and mechanisms in detail.

Patterns of development of cardiovascular disorders in patients with COVID-19 (brief review)

Introduction. Cardiovascular diseases remain the leading cause of death, both in Russia and in most other countries, and the problem of cardiovascular disorders in patients with COVID-19 is currently extremely important.Aim. To summarize the literature data on patterns of development of cardiovascular disorders in patients with COVID-19.Results. The article presents a literature review of the PubMed and Google Scholar databases on the patterns of development of cardiovascular disorders in patients with COVID-19. The pathogenetic relationship of the viral spike S-protein with angiotensin-converting enzyme 2 in the mechanisms of regulation of the cardiovascular and immune systems was shown. The role of pro-inflammatory cytokines in the formation of inflammation and fibrosis in cardiovascular pathology has been determined. The changes in the cardiovascular system against the background of COVID-19 were demonstrated. The basic principles of the interaction of the SARS-CoV-2 virus with endotheliocytes and cardiomyocytes, the mechanisms of inflammatory reactions that underlie the development of cardiovascular pathology in COVID-19 are described.Conclusion. An analysis of current data regarding damage to the cardiovascular system in COVID-19 led to the conclusion that, despite considerable achievements in this field of research, many aspects are not fully understood and require further study. The practical significance of this review is determined in the identification of potential therapeutic targets for the prevention of complications in COVID-19, as well as in expanding the possibilities of diagnosing SARS-CoV-2. Probably the crucial importance to reduce complications, as well as associated mortality, is the development of an effective method for modulating the immune response.

MiR-331-3p Inhibits Inflammatory Response after Intracerebral Hemorrhage by Directly Targeting NLRP6.

Background The mechanism of inflammatory reaction after intracerebral hemorrhage remains unclear, which to some extent restrains the therapeutic development of hemorrhagic stroke. The present study attempts to verify whether NLRP6 plays an important role in inflammatory reaction after intracerebral hemorrhage and identify the critical microRNA during the process. Methods Suitable simulated cerebral hemorrhage environments were established in vitro and in vivo. BV2 cells were treated with hemin to induce cell damage. Collagenase was used to establish a model of mouse cerebral hemorrhage. The relationship among NLRP6, miR-331-3p, and the corresponding inflammatory expression was closely observed during this process. Techniques, such as western blot, real-time quantitative PCR, immunofluorescence, and immunocytochemistry, were used to detect the expression of relative genes and molecules in the in vitro and in vivo models. Results Downregulated miR-331-3p increased the expression of NLRP6 and alleviated the expression of TNF-α and IL-6. The neurological function recovery of mice was promoted after intracerebral hemorrhage. Conclusion miR-331-3p regulated the inflammatory response after cerebral hemorrhage by negatively regulating the expression of NLRP6.

Deubiquitinase Inhibitor b-AP15 Attenuated LPS-Induced Inflammation via Inhibiting ERK1/2, JNK, and NF-Kappa B.

b-AP15 is a deubiquitinase (DUB) inhibitor of 19S proteasomes, which in turn targets ubiquitin C-terminal hydrolase 5 (UCHL5) and ubiquitin-specific peptidase 14 (USP14). Nuclear factor kappa B (NF-κB) is closely linked to cellular response in macrophages when the organism is in the state of microbial infection, and it acts as a vital part in the mechanism of inflammatory reaction. However, the molecular mechanism by which DUB inhibitors, especially b-AP15, regulates inflammation remains poorly understood. This study aimed to investigate the relationship between b-AP15 and inflammation. The results showed that b-AP15 treatment significantly reduced the amounts of inflammatory indicators, such as tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) in lipopolysaccharide (LPS)-stimulated THP-1 and macrophages. Meanwhile, similar results were obtained from in vivo experiments. In addition, b-AP15 also significantly improved the survival rate of sepsis mouse via high-density LPS mediation. Furthermore, b-AP15 also inhibited the ERK1/2 and JNK phosphorylation, increased IκBα levels, and inhibited NF-κB p65 by removing them from the cytoplasm into the nucleus. All these findings suggested that b-AP15 has anti-inflammatory action and acts as a potential neoteric target drug for treating microbial infection.

MiR-16-1 expression, heat shock protein 70 and inflammatory reactions in astrocytes of mice with epilepsy induced by encephalitis B virus infection.

The upregulation of miR-16-1 expression and heat shock protein 70 (HSP70) and inflammatory reaction mechanism in astrocytes of mice with epilepsy induced by encephalitis B virus infection were studied. Six-to-eight-week-old healthy male C57BL/6 mice received intraperitoneal injection of pilocarpine (320–340 mg/kg, 40 mg/ml) to induce status epilepsy. After 7 days, mice were inoculated with 100 µl Dulbecco's modified Eagle's medium (DMEM) in the neck, including 6.25×23 PFU Japanese encephalitis virus P3 wild strain. The experiment was divided into 4 groups, including, the healthy control group, the epilepsy model group, the model group + negative inoculation group and the virus infection group with 10 mice in each group. The healthy control group received intraperitoneal injection of the same amount of normal saline; the model group + negative inoculation group was injected with the same amount of DMEM without P3. One and three days after infection, 5 mice from each group were sacrificed, hippocampus tissues were obtained and astrocytes were isolated. After purification, glial fibrillary acidic protein was identified by immunohistochemical staining. Infected glial cells were detected by P3 antigen of immunofluorescence staining. RT-PCR method was used to detect the expression of miR-16-1 mRNA in astrocytes. Western blot analysis was used to detect the expression of HSP70. ELISA method was used to detect the levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α and nuclear factor-κB (NF-κB) inflammatory factors in tail vein blood. Level of expression of miR-16-1 mRNA, HSP70 as well as IL-6, TNF-α and NF-κB inflammatory factor levels of virus infected mice of 1 and 3 days were significantly higher (P<0.05) than those of model group and negative inoculation group and lowest in control group. In conclusion, the level of expression of miR-16-1 and HSP70 can be increased by the infection of Japanese encephalitis virus on the astrocytes of mice with epilepsy, to promote the expression of IL-6, TNF-α and NF-κB of inflammatory factors.

Epochal neuroinflammatory role of high mobility group box 1 in central nervous system diseases

The central nervous system (CNS) is enriched with a developed reaction reserve dubbed “neuroinflammation”, which facilitates it to cope with pathogens, toxins, traumata and degeneration. Inflammation is a significant biological activity in reaction to injury, infection, and trauma agonized by cells or tissues. A positive inflammatory reaction mechanism removes attacking pathogens, initiating wound healing and angiogenesis. The High Mobility Group Box 1 (HMGB1) protein is abundant and ubiquitous nuclear proteins that bind to DNA, nucleosome and other multi-protein complexes in a dynamic and reversible fashion to regulate DNA processing in the context of chromatin. Complex genetic and physiological variations as well as environmental factors that drive emergence of chromosomal instability, development of unscheduled cell death, skewed differentiation, and altered metabolism are central to the pathogenesis of human diseases and disorders. HMGB1 protein, senses and coordinates the cellular stress response and plays a critical role not only inside of the cell as a DNA chaperone, chromosome guardian, autophagy sustainer, and protector from apoptotic cell death, but also outside the cell as the prototypic damage associated molecular pattern molecule (DAMP). This DAMP, in conjunction with other factors such as cytokine, chemokine, and growth factor activity, orchestrating the inflammatory and immune response. All of these characteristics make HMGB1 a critical molecular target in multiple human diseases including infectious diseases, ischemia, immune disorders, neurodegenerative diseases, metabolic disorders, and cancer. With regards to these various disease condition above, our review focus on the role of HMGB1 and CNS Diseases.

Histopathology of nasal mucosa and inflammatory changes in nasal wash of symptomatic rhinitis patients

This article was originally published online on 8 April 2015 The extent of epithelial damage in allergic (AR) and nonallergic rhinitis (NAR) and its association to inflammatory changes in nasal washes (NW) are not fully understood. Investigate the relationship of inflammatory cells in NW and the level of epithelial damage and basement membrane thickening (BMT) of the upper airway mucosa Total nasal symptom score (TNSS), NW and turbinate biopsy specimens were obtained from 36 AR and 20 NAR patients. Atopic patients had positive skin prick test to D.pteronyssinus (35/97%) and L.perenne (18/50%) extracts from Hollister-Stier. Total and differential cell counts were evaluated by a quantitative method of nasal cytology; albumin and IL-8 concentrations were determined in the supernatant of NW. The epithelium damage and BMT were assessed on H&E-stained sections by staging system. Statistical analysis was performed by nonparametric Mann-Whitney U test for comparison between cell counts and differences in frequencies by Fisher exact test. The median age was 24.5ys. (14-58). TNSS was higher in AR (9 [1-18]) as compared to NAR (6.5 [0-12]) (p=0.01). Total cell and neutrophil counts, as well as albumin and IL-8 levels were not different in NW of AR and NAR patients. Median eosinophil count in nasal fluid (ECNF) was higher in AR (3% [0-66]) than in NAR (1% [0-21]) (p<0.01). ROC curve analysis and AUC for ECNF accuracy in distinguishing AR from NAR, has showed a cut-off value of 4%, AUC=0.71. ECNF was ≥4% in 44% of AR and 20% of NAR patients; at this point the probability of atopy was 80%, with 44% sensitivity and 90% specificity. Epithelial damage was more frequent in AR (94%) than in NAR (65%) (p<0,01). According to the presence of BMT, NW of AR patients without BMT had higher median eosinophil (3% [1-7]) and neutrophils (47.5% [0-87]) counts compared to eosinophils (1% [0-4]) and neutrophils (12% [0-23]) counts in NAR. On the other hand, in the presence of BMT, there were no differences in the NW of AR and NAR patients. The intragroup analysis showed that neutrophil count was higher in NW of NAR patients with BMT (45% [12-83]) than without BMT (12% [0-23]) (p<0.01). The best cut-off value of ECNF to discriminate atopic patients was 4%. Despite of differences in mechanisms of inflammatory reactions in rhinitis, airway remodeling assessed by BMT is associated with similar cellularity in NW of both AR and NAR.

Abstract P159: Th17 Cells Are Indispensable for Cardiac Inflammation in Autoimmune Myocarditis

Background: Chronic inflammation is closely associated with heart failure; however, the molecular and cellular mechanisms of inflammatory reactions remain to be fully elucidated. Interleukin(IL)-17 is a pro-inflammatory cytokine that is produced by Th17 cells. Th17 cells are induced by IL-6 and transforming growth factor(TGF-β), through up-regulation of its specific transcriptional factor, retinoic acid receptor-related orphan nuclear receptor(ROR)γt. Th17 cells are reported to participate in pathogenesis of chronic inflammatory disease. In this study, we examined the functional roles of Th17 signaling in cardiac inflammation using murine experimental autoimmune myocarditis(EAM) model. Methods and Results: EAM was induced in wild-type(WT) and/or RORγt-eGFP knock-in Balb/c mice by immunization twice with α-myosin heavy chain peptide. Three weeks after the first immunization, the mRNA expression of RORγt was up-regulated and correlated with the disease severity in heart. Additionally, in immunostaining and flow cytometry analysis, we observed a significant number of Th17 cells among inflammatory cells infiltrating myocardium from WT and RORγt-eGFP knock-in heterozygous mice. These data showed that Th17 cells were remarkably recruited in EAM heart. Moreover, depression of Th17 differentiation suppressed disease severity completely with inhibition of RORγt and IL-17 transcriptional activity, whereas IL-17 neutralizing antibody to lesser extent. Finally, RORγt-eGFP knock-in homozygous mice were protected from cardiac inflammation. Conclusion: Our results indicated that Th17 activation through RORγt pathway is a critical mechanism for the development of myocarditis. However, IL-17 is not crucial for induction of EAM, suggesting that other Th17 producing pro-inflammatory cytokines are involved. It could be proposed that Th17 cells are novel therapeutic target against chronic inflammation in heart.

Regulation of atherosclerotic plaque growth and stability by testosterone and its receptor via influence of inflammatory reaction

Background Platelets play crucial roles in the development of arterial thrombosis and other pathophysiologies leading to clinical ischemic events. Defective regulation of platelet activation/aggregation is a predominant cause for arterial thrombosis. The purposes of the study are to determine whether atherosclerotic plaque growth or stability is regulated by physiological doses of testosterone via its receptor, and to further investigate the possible mechanisms of inflammatory reaction. Methods and results We prepared models of castrated male rabbits. Pathological sections of aorta were performed hematoxylin–eosin (HE) staining and Masson's trichrome staining. Total plasma testosterone was measured using ADVIA Centaur® Immunoassay System (Bayer, Germany). Serum TNF α and IL 6 were assayed using radio-immunoassay kit and serum sICAM-1 and MMP 2 were measured using ELISA kit. Our results showed that castration significantly lowered plasma testosterone levels, whereas testosterone replacement at a dose of 6 mg/kg/two-week restored circulating testosterone to physiological levels, without being altered by treatment with flutamide (a testosterone receptor inhibitor). Testosterone undecanoate replacement reduced the plaque area and the aortic intimal thickness, whereas the fibrous cap thickness and collagen contents increased in castrated rabbits. However, the presence of flutamide increased the plaque area and the aortic intimal thickness, whereas the fibrous cap thickness and collagen contents decreased in castrated rabbits again. Moreover, the levels of serum TNF α, IL 6, sICAM and MMP 2 increased in cholesterol-rich diet rabbits as compared with standard diet rabbits. Castration caused increases in the levels of serum TNF α, IL 6, sICAM and MMP 2 in castrated rabbits as compared with sham-operated rabbits. Treatment of testosterone undecanoate reduced the levels of serum TNF α, IL 6, sICAM and MMP 2 in castrated rabbits, while the presence of flutamide increased the levels of serum TNF α, IL 6, sICAM and MMP 2 again. Conclusion Replacement of physiological testosterone regulates atherosclerotic plaque growth and stability via its receptor in castrated rabbits, which is probably related to their influence on inflammatory reaction.

Acute inflammatory reaction mechanism from the viewpoint of cytokine.

Acute inflammatory reaction mechanism from the viewpoint of cytokine.