scholarly journals The role of HMGB1 in invasive Candida albicans infection

2020 ◽  
Author(s):  
Jiaojiao Wang ◽  
Chuanxin Wu ◽  
Yunying Wang ◽  
Chongxiang Chen ◽  
Jing Cheng ◽  
...  
Keyword(s):  
Ethyl Pyruvate ◽  
Survival Rates ◽  
High Mobility ◽  
Serum Levels ◽  
Bacterial Sepsis ◽  
Reactive Protein ◽  
Tnf Α ◽  
Hmgb1 Expression ◽  
Factor Α

AbstractBackgroundHigh mobility group box 1 (HMGB1) is an important “late” inflammatory mediator in bacterial sepsis. Ethyl pyruvate (EP), an inhibitor of HMGB1, can prevent bacterial sepsis by decreasing HMGB1 levels. However, the role of HMGB1 in fungal sepsis is still unclear. Therefore, we investigated the role of HMGB1 and EP in invasive C. albicans infection.MethodsWe measured serum HMGB1 levels in patients with sepsis with C. albicans infection and without fungal infection, and control subjects. We collected clinical indices to estimate correlations between HMGB1 levels and disease severity. Furthermore, we experimentally stimulated mice with C. albicans and C. albicans + EP. Then, we examined HMGB1 levels from serum and tissue, investigated serum levels of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), determined pathological changes in tissues, and assessed mortality.ResultsSerum HMGB1 levels in patients with severe sepsis with C. albicans infection were elevated. Increased HMGB1 levels were correlated with procalcitonin (PCT), C-reactive protein (CRP), 1,3-β-D-Glucan (BDG) and C. albicans sepsis severity. HMGB1 levels in serum and tissues were significantly increased within seven days after mice were infected with C. albicans. The administration of EP inhibited HMGB1 levels, decreased tissue damage, increased survival rates and inhibited the release of TNF-α and IL-6.ConclusionsHMGB1 levels were significantly increased in invasive C. albicans infections. EP prevented C. albicans lethality by decreasing HMGB1 expression and release. HMGB1 may provide an effective diagnostic and therapeutic target for invasive C. albicans infections.

Genetic Variation in TNF-α, its Relation with Inflammatory Biomarkers and Susceptibility to Rheumatoid Arthritis

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Khadiga Ahmed Ismail
Keyword(s):  
Rheumatoid Arthritis ◽  
Serum Level ◽  
Functional Disability ◽  
Serum Levels ◽  
Amplification Refractory Mutation System ◽  
Reactive Protein ◽  
Tnf Α ◽  
Mutation System ◽  
Potential Factor ◽  
Factor Α

Background: Tumor necrosis Factor-α (TNF-α) is encoded and controlled by TNF-α gene, which is involved in rheumatoid arthritis (RA) susceptibility. This research aimed to identify genetic variations of TNF-α (G308A) and to establish its association with inflammatory markers in Rheumatoid Arthritis predisposition. Methods: In the present study, fifty RA patients and fifty volunteers were involved and evaluated for the C-reactive protein, rheumatoid factor, and TNF-α were estimated by ELISA, Erythrocyte Sedimentation Rate (ESR) by Wintergreen method and for TNF-α-308 G>A polymorphism by polymerase chain reaction with amplification refractory mutation system (PCR-ARMS). Results: The CRP, RF, ESR and TNF-α were significantly elevated in RA patients relative to controls. The serum level TNF-α was also significantly elevated in female patients and in patients ≥50 years. Analysis of TNF-308 gene polymorphism revealed that GG genotypes were more prevalent in RA patients than in the healthy individuals and that GG genotype may be a potential factor to RA. The G allele was more common in RA than in the control. Elevated TNF-α serum levels were significantly associated the GG genotype and functional disability in RA patients. Conclusion: TNF-α promoter 308polymorphism GG genotype may be considered as a risk factor for RA and the TNF-α serum level was significantly related to the functional disability in the disease.

scholarly journals Systemic Inflammation and Clinical Outcomes in COVID-19: a retrospective study

2020 ◽  
Author(s):  
Meijia Wang ◽  
Zhenli Huang ◽  
Kun Tang ◽  
Pengfei Gao ◽  
Yanjiao Lu ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Clinical Outcomes ◽  
Systemic Inflammation ◽  
Trial Registration ◽  
Inflammatory Factors ◽  
Reactive Protein ◽  
Tnf Α ◽  
Registration Number ◽  
Factor Α

Abstract Background：COVID-19 causes epidemics and pandemics worldwide, but the role of pathophysiological parameters particularly systemic inflammation in COVID-19 has not been understood. We aimed to investigate clinical outcomes in view of systemic inflammation in COVID-19.Methods：In this retrospective study, the demographic and clinical data of 225 confirmed COVID-19 cases on admission at Tongji Hospital from January 28 to February 15, 2020, were extracted and analyzed. These patients were categorized by inflammation state on the basis of the expression of inflammatory factors or classified as severe and non-severe according to 2019 American Thoracic Society / Infectious Disease Society of America guidelines.Results: Among 225 patients with confirmed COVID-19, 155 patients (68.9%) categorized into hyperinflammation group and 70 (31.1%) were non- hyperinflammation group. Compared to non-hyperinflammation group, hyperinflammation group more frequently had chest tightness/dyspnea and lymphopenia, aberrant multiple indexes of organ function including the heart, liver, kidney, and coagulation, with higher level of C-reactive protein (hsCRP) as well as interleukin (IL)-6, IL-8, tumour necrosis factor α (TNF-α), etc. Hyperinflammation group were more likely to admit to intensive care unit (ICU) (52.3% vs 5.7%), receive ventilation (84.5% vs 10.0%) and be with higher mortality (44.5% vs 5.7%) than non-hyperinflammation group. The mortality of severe patients with hyperinflammation (60/99, 60.6%) was significantly higher than without hyperinflammation (2/20, 10.0%). Non-severe patients with hyperinflammation even tended to have higher mortality (9/56, 16.1%) than those in severe cases without hyperinflammation (2/20, 10%).Conclusion: Excessive systemic inflammation was correlated highly with poor clinical outcomes in COVID-19, particularly in severe cases. Non-severe patients with hyperinflammation even tended to have higher mortality than those in severe cases without hyperinflammation.Trial registration: This is a retrospective observational study without a trial registration number.

scholarly journals The role of HMGB1 in invasive Candida albicans infection

2020 ◽  
Author(s):  
Jiaojiao Wang ◽  
Chuanxin Wu ◽  
Yunying Wang ◽  
Chongxiang Chen ◽  
Jing Cheng ◽  
...  
Keyword(s):  
Severe Sepsis ◽  
Fungal Infection ◽  
Disease Severity ◽  
Therapeutic Target ◽  
Ethyl Pyruvate ◽  
Bacterial Sepsis ◽  
Infection Group ◽  
Protein Levels ◽  
Tnf Α

Abstract Background: High mobility group box 1 (HMGB1), an important “late” inflammatory mediator, is a therapeutic target for bacterial sepsis. Ethyl pyruvate (EP) has anti-inflammatory effects, and prevents bacterial sepsis by decreasing HMGB1 levels. However, the role of HMGB1 in fungal sepsis is still unclear. Therefore, we investigated HMGB1 mRNA and protein levels in serum and tissue from patients and mice with invasive C. albicans infection. We explored the anti-HMGB1 effects of EP, which may be of benefit in the diagnosis and treatment of invasive C. albicans infections. Methods: We measured serum HMGB1 mRNA and protein levels in four different patient groups: 23 control subjects (group 1), 35 patients with sepsis without fungal infection (group 2), 35 patients with severe sepsis without fungal infection (group 3), and 23 patients with severe sepsis with C. albicans infection (group 4). We collected clinical indices to estimate correlations between HMGB1 levels and disease severity. Furthermore, we experimentally stimulated mice with C. albicans and C. albicans + EP, and examined HMGB1 mRNA and protein levels from serum and tissue. We determined liver and kidney functions, investigated pathological changes in tissues and assessed mortality. We also investigated serum levels of the proinflammatory cytokines, tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) in these animals. Results: Serum HMGB1 mRNA and protein levels in patients with severe sepsis with C. albicans infection were elevated. Increased HMGB1 levels were correlated with procalcitonin (PCT), C-reactive protein (CRP), 1,3-β-D-Glucan (BDG) and C. albicans sepsis severity. HMGB1 mRNA and protein levels in serum and tissues were significantly increased within seven days after mice were infected with C. albicans. The administration of EP inhibited HMGB1 levels, decreased tissue damage, increased survival rates and inhibited the release of TNF-α and IL-6.Conclusions: Increased HMGB1 levels in patients with severe sepsis with C. albicans infection were positively correlated with PCT, CRP, BDG, and disease severity. EP prevented C. albicans lethality by decreasing HMGB1 expression and release. We suggest that HMGB1 plays a vital role in invasive C. albicans infections and may provide an effective diagnostic and therapeutic target for such infections in clinical settings.

Psoriasis: Tumor Necrosis Factor –α, Interleukin 18, C Reactive Protein Polymorphism , and Osteopontin Role

2018 ◽  
Vol 1 (1) ◽  
pp. 58-62
Author(s):  
Ibrahim Abed
Keyword(s):  
Skin Condition ◽  
Chronic Inflammatory Disease ◽  
Systemic Complications ◽  
Reactive Protein ◽  
Tnf Α ◽  
Inflammatory Processes ◽  
Chronic Skin ◽  
Abnormal Lipid Metabolism ◽  
Factor Α

  Background: Psoriasis is a common chronic skin disorder with prevalence of 2.7% in Iraqi community. Many factors affect the prevalence of psoriasis which include genetic, environmental, infectious, immunological, biochemical, endocrinological and psychological. Psoriasis is a chronic inflammatory disease with unknown exact pathogenesis, which may be started as skin condition that subsequently associated with systemic complications. The recurrent proliferative inflammatory processes in subject with psoriasis may lead to abnormal lipid metabolism and associated with cardiovascular diseases. Gene polymorphisms represent either a protective or risk factors for development of psoriasis and cardiovascular disease. Aim of the Study: The aim of the present study is to provide a picture about the association between psoriasis and atherosclerosis. Objectives: To: 1. Estimate the prevalence of impending atherosclerosis in patients with psoriasis. 2. Identify the pattern of association among inflammatory markers in one hand and lipoproteins as traditional markers in another. 3. Clarify the risk assessment of atherosclerosis in patients with psoriasis using multi- biomarkers score. 4. Appraise the inter – traditional and new markers. 5. Evaluate the role of IL-18, TNF -α, osteopontin in the pathogenesis of psoriasis and atherosclerosis. 6. Illustrate the association between disease susceptibility and different gene polymorphism such as IL-18, TNF-α and CRP.  

scholarly journals Ethyl pyruvate ameliorate inflammatory response of sinonasal mucosa by inhibiting HMGB1 in rats with acute rhinosinusitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiang Liang ◽  
Yang Shen ◽  
Xiaowei Zhang ◽  
Guangxiang He ◽  
Guolin Tan
Keyword(s):  
Inflammatory Response ◽  
Ethyl Pyruvate ◽  
Intervention Group ◽  
Serum Levels ◽  
Nasal Sinus ◽  
Bacterial Colony ◽  
Acute Rhinosinusitis ◽  
Tnf Α ◽  
Hmgb1 Expression ◽  
Sinonasal Mucosa

AbstractHigh mobility group box 1 (HMGB1) has been known to involve in the pathogenesis of many inflammatory diseases. The aim of this study was to establish animal model of acute rhinosinusitis (ARS), and determine whether ethyl pyruvate (EP) attenuate inflammatory response of sinonasal mucosa by inhibiting HMGB1 in ARS animals. Thirty-six Sprague Dawley (SD) rat were used as follows: six normal controls without intervention (group 1); thirty rats were used for establishment of ARS rats model by nasal insertion of Merocel sponge, and model rats without any treatments (group 2), treated with nasal drops of sterile saline (group 3), 10 μl EP (group 4), and 20 μl EP (group 5), twice a day for 5 days, respectively. Bacterial culture was done regularly and the main bacterial strains were identified using matrix-assisted laser desorption/ionization time of flight mass spectrometry. HMGB1 expression in sinonasal mucosa was detected by immunohistochemistry and RT-PCR. Serum levels of HMGB1, IL-6, and TNF-α were determined by ELISA. Data from 29 of 36 rats that had completed research were analyzed. Bacterial colony formation unit (CFU) of nasal secretion was significantly higher in each group of ARS rats compared with controls (p < 0.001). ARS rats treated with EP had only slightly decreased CFU, but significantly attenuated inflammatory response of sinonasal mucosa and decreased HMGB1 expression compared to those treated with saline alone (p < 0.001). Serum levels of HMGB1, IL-6 and TNF-α were significantly higher in ARS rats compared to controls, and decreased by EP treatments (p < 0.001). Nasal sponge packing led to acute inflammatory response of nasal sinus in rats, and increased the expression of HMGB1, IL-6, and TNF-α. Nasal drops with EP could attenuate the inflammation of sinonasal mucosa through inhibiting the expression of HMGB1, IL-6 and TNF-α in ARS rats.

scholarly journals Manipulation of Quercetin and Melatonin in the Down-Regulation of HIF-1α, HSP-70 and VEGF Pathways in Rat’s Kidneys Induced by Hypoxic Stress

Dose-Response ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 155932582094979
Author(s):  
Aliah R. Alshanwani ◽  
Sameerah Shaheen ◽  
Laila M. Faddah ◽  
Ahlam M. Alhusaini ◽  
Hanaa M. Ali ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Histopathological Examination ◽  
Hemoglobin Concentration ◽  
Vascular Endothelial ◽  
Hsp 70 ◽  
Reactive Protein ◽  
Defensive Role ◽  
Factor Α ◽  
Endothelial Growth Factor

Hypoxia may lead to inflammatory responses by numerous signaling pathways. This investigation intended to inspect the defensive role of Quercetin (Quer) and/ or Melatonin (Mel) against reno toxicity induced by Sodium nitrite (Sod ntr). Sod ntr injection significantly decreased blood hemoglobin concentration (Hb) with a concurrent increase in serum tumor necrosis factor- α, interleukin-6, C-reactive protein, creatinine, and urea levels. Over protein-expression of vascular endothelial growth factor and heat shock, protein-70 and mRNA of HIF-1α were also observed. Pretreatment of the Sod ntr- injected rats with the aforementioned antioxidants; either alone or together significantly improved such parameters. Histopathological examination reinforced the previous results. It was concluded that the combined administration of Quer and Mel may be useful as a potential therapy against renal injury induced by Sod ntr. HIF-1α and HSP-70 are implicated in the induction of hypoxia and its treatment.

C1QTNF6 participates in the pathogenesis of PCOS by affecting the inflammatory response of granulosa cells

2021 ◽  
Author(s):  
Sisi Yan ◽  
Jinli Ding ◽  
Yi Zhang ◽  
Jiayu Wang ◽  
Sainan Zhang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Mouse Models ◽  
Granulosa Cells ◽  
Polycystic Ovary ◽  
Serum Levels ◽  
Inflammatory Factors ◽  
Low Grade ◽  
Reactive Protein ◽  
Reproductive Endocrine ◽  
Factor Α

Abstract Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease. It has been reported that chronic low-grade inflammation might participate in its pathogenesis. C1q and TNF related 6 (C1QTNF6) is a newly identified adiponectin paralog associated with inflammation. The aim of the present study was to investigate the role of C1QTNF6 in the development of chronic inflammation in PCOS and the underlying molecular mechanism. After analyzing the expression of C1QTNF6 in the serum and granulosa cells (GCs) of PCOS patients and healthy controls, we verified the roles of C1QTNF6 in inflammation through dehydroepiandrosterone-induced PCOS mouse models and cell models of lipopolysaccharide (LPS)-induced inflammation. The results demonstrated that C1QTNF6 expression in the serum and GCs of patients with PCOS was significantly elevated compared with those of the controls, and similar results were observed in the serum and ovary of PCOS mouse models. In PCOS mice and C1QTNF6-overexpressing PCOS mice, serum levels of pro-inflammatory factors including C-reactive protein (CRP), interleukin 6 (IL6) and tumor necrosis factor-α (TNFα) were increased, while the opposite effects were observed when C1QTNF6 was downregulated in PCOS mice. Furthermore, C1QTNF6 overexpression upregulated the levels of TNFα, IL6, and CRP and activated the AKT/NF-κB pathway in LPS-treated KGN cells, whereas C1QTNF6 knockdown and BAY-117082 (an NF-κB inhibitor) treatment resulted in the opposite effects. Taken together, our results indicate that C1QTNF6 is involved in the pathogenesis of PCOS by affecting the inflammatory response via the AKT/NF-κB signaling pathway.

scholarly journals Rifaximin as a Potential Treatment for IgA Nephropathy in a Humanized Mice Model

2021 ◽  
Vol 11 (4) ◽  
pp. 309
Author(s):  
Vincenzo Di Leo ◽  
Patrick J. Gleeson ◽  
Fabio Sallustio ◽  
Carine Bounaix ◽  
Jennifer Da Silva ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Serum Levels ◽  
Humanized Mice ◽  
Polymeric Immunoglobulin Receptor ◽  
Oral Antibiotic ◽  
Mice Model ◽  
Immunoglobulin Receptor ◽  
Tnf Α ◽  
Factor Α ◽  
Growth Of Bacteria

IgA Nephropathy (IgAN) is the most common glomerulonephritis worldwide, characterized by the mesangial deposition of abnormally glycosylated IgA1 (Gd-IgA). The production of Gd-IgA occurs in mucose-associated lymphoid tissue (MALT). The microbiota plays a role in MALT modulation. Rifaximin (NORMIX®), a non-absorbable oral antibiotic, induces positive modulation of the gut microbiota, favoring the growth of bacteria beneficial to the host. Here, we evaluate the effect of rifaximin on a humanized mice model of IgAN (α1KI-CD89Tg). Methods: The α1KI-CD89Tg mice were treated by the vehicle (olive oil) or rifaximin (NORMIX®). Serum levels of hIgA, hIgA1–sCD89, and mIgG–hIgA1 immune complexes were determined. Glomerular hIgA1 deposit and CD11b+ cells recruitment were revealed using confocal microscopy. Furthermore, the mRNA of the B-Cell Activating Factor (BAFF), polymeric immunoglobulin receptor (pIgR), and Tumor Necrosing Factor-α (TNF-α) in gut samples were detected by qPCR. Results: Rifaximin treatment decreased the urinary protein-to-creatinine ratio, serum levels of hIgA1–sCD89 and mIgG–hIgA1 complexes, hIgA1 glomerular deposition, and CD11b+ cell infiltration. Moreover, rifaximin treatment decreased significantly BAFF, pIgR, and TNF-α mRNA expression. Conclusions: Rifaximin decreased the IgAN symptoms observed in α1KI-CD89Tg mice, suggesting a possible role for it in the treatment of the disease.

scholarly journals LPS Primes Brain Responsiveness to High Mobility Group Box-1 Protein

2021 ◽  
Vol 14 (6) ◽  
pp. 558
Author(s):  
Verena Peek ◽  
Lois M. Harden ◽  
Jelena Damm ◽  
Ferial Aslani ◽  
Stephan Leisengang ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Area Postrema ◽  
High Mobility ◽  
High Mobility Group ◽  
Direct Access ◽  
Significant Release ◽  
Factor Α ◽  
Culture Supernatants

High mobility group box (HMGB)1 action contributes to late phases of sepsis, but the effects of increased endogenous plasma HMGB1 levels on brain cells during inflammation are unclear. Here, we aimed to further investigate the role of HMGB1 in the brain during septic-like lipopolysaccharide-induced inflammation in rats (LPS, 10 mg/kg, i.p.). HMGB-1 mRNA expression and release were measured in the periphery/brain by RT-PCR, immunohistochemistry and ELISA. In vitro experiments with disulfide-HMGB1 in primary neuro-glial cell cultures of the area postrema (AP), a circumventricular organ with a leaky blood–brain barrier and direct access to circulating mediators like HMGB1 and LPS, were performed to determine the direct influence of HMGB1 on this pivotal brain structure for immune-to-brain communication. Indeed, HMGB1 plasma levels stayed elevated after LPS injection. Immunohistochemistry of brains and AP cultures confirmed LPS-stimulated cytoplasmatic translocation of HMGB1 indicative of local HMGB1 release. Moreover, disulfide-HMGB1 stimulation induced nuclear factor (NF)-κB activation and a significant release of interleukin-6, but not tumor necrosis factor α, into AP culture supernatants. However, only a few AP cells directly responded to HMGB1 with increased intracellular calcium concentration. Interestingly, priming with LPS induced a seven-fold higher percentage of responsive cells to HMGB1. We conclude that, as a humoral and local mediator, HMGB1 enhances brain inflammatory responses, after LPS priming, linked to sustained sepsis symptoms.

The Role of Tumor Necrosis Factor-α (TNF-α) Polymorphisms in Gastric Cancer: a Meta-Analysis

2021 ◽  
Author(s):  
Maryam Gholamalizadeh ◽  
Samaneh Mirzaei Dahka ◽  
Hadi Sedigh Ebrahim-Saraie ◽  
Mohammad Esmail Akbari ◽  
Azam Pourtaheri ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Meta Analysis ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor
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