International Journal of Inflammation最新文献

Different protein degradation pathways exist in cells. However, the bulk of cellular proteins are degraded by the ubiquitin-proteasome system (UPS), which is one of these pathways. The upkeep of cellular protein homeostasis is facilitated by the ubiquitin-proteasome system, which has a variety of important functions. With the emergence of eukaryotic organisms, the relationship between ubiquitylation and proteolysis by the proteasome became apparent. Severe acute respiratory syndrome coronavirus-2 (SARS-Coronavirus-2) hijacks the ubiquitin-proteasome system and causes their viral proteins to become ubiquitinated, facilitating assembly and budding. Ubiquitination of the enzyme keratin-38 (E-K38) residue gave the virion the ability to engage with at least one putative cellular receptor, T-cell immunoglobin-mucin (TIM-1), boosting virus entry, reproduction, and pathogenesis. A fraction of infectious viral particles produced during replication have been ubiquitinated. The ubiquitin system promotes viral replication. In order to replicate their viral genome after entering the host cell, viruses combine the resources of the host cell with recently generated viral proteins. Additionally, viruses have the ability to encode deubiquitinating (DUB)-active proteins that can boost viral replication through both direct and indirect means. The SARS-Coronavirus-2 papain-like protease (PLpro) protein is a DUB enzyme that is necessary for breaking down viral polyproteins to create a working replicase complex and promote viral propagation. The ubiquitin-like molecule interferon-stimulated gene 15 (ISG15), which is likewise a regulator of the innate immune response and has antiviral characteristics, can also be broken down by this enzyme. However, limiting the E1-activating enzyme's ability to suppress the ubiquitination pathway prevented virus infection but did not prevent viral RNA genome translation. Numerous investigations have revealed that the use of proteasome inhibitors has a detrimental effect on the replication of SARS-Coronavirus-2 and other viruses in the host cell. Studies have shown that the use of proteasome inhibitors is also known to deplete free cellular ubiquitin, which may have an impact on viral replication and other vital cellular functions.

In traditional Cameroonian medicine, to relieve many inflammations, parts of Vernonia guineensis, are very widely used. This study considered the evaluation of acute toxicity and anti-inflammatory properties of the hydroethanolic extract of the roots of Vernonia guineensis. In an acute toxicity study, 250, 2500, and 5000 mg/kg were administered orally to mice in a single dose, and general behavior, adverse effects, and mortality were monitored. In vitro and in vivo anti-inflammatory tests were performed, and then histological, serum, hematological, and oxidative stress parameters have been evaluated. In an acute toxicity, all groups revealed neither mortality nor any significant alteration in behavior; only drowsiness, sedation, and lethargy were observed at 5000 mg/kg. For in vitro tests, the extract inhibited anti-inflammatory activity. In the formalin test, at 250 mg/kg, the extract inhibited edema with a percentage of 56.41% (4^th hour) in an acute treatment and 74.44% (10^th day). Joint edema was reduced by 67.24% (24^th hour) in a single treatment and by 74.25% (7^th day) in repeated treatment. The extract caused an increase in red blood cell, hemoglobin, and serum protein levels and reduced the white blood cells as well as the activities of alkaline phosphatase and alanine aminotransferase. The extract modulated oxidative stress parameters in the brain, spinal cord, liver, and kidneys. The extract protected the joint by reducing the bone and cartilage erosion. The present work highlights the anti-inflammatory, antioxidant, and antianemic properties of the hydroethanolic extract of the roots of Vernonia guineensis, which supports its empirical use in traditional medicine for the treatment of inflammatory pathologies.

Cigarette smoke (CS) was known for its effect of increasing oxidative stress that could trigger tissue injury and endothelial dysfunction mediated by free radicals and reactive oxygen species (ROS). ROS itself is a key signaling molecule that plays a role in the development of inflammatory disorders. Nuclear factor erythroid2 related factor2 (Nrf2) is the main regulator of antioxidant cellular response to cell and tissue-destroying components caused by CS. Nrf2 protein that is significantly activated in the smokers' small airway epithelium is followed by a series of gene expression changes in the same cells. This study aims to observe differentially expressed genes (DEGs) in the human small airway epithelium of smokers compared to genes whose expression changes due to astaxanthin (AST) treatment, an antioxidant compound that can modulate Nrf2. Gene expression data that was stored in the GEO browser (GSE 11952) was analyzed using GEO2R to search for DEG among smokers and nonsmokers subject. DEG was further compared to those genes whose expression changes due to astaxanthin treatment (AST) that were obtained from the Comparative Toxicogenomics Database (CTD; https://ctdbase.org/). DEG (p < 0.05) analysis result shows that there are 23 genes whose expression regulation is reversed compared to gene expression due to AST treatment. The gene function annotations of the 23 DEGs showed the involvement of some of these genes in chemical and oxidative stress, reactive oxygen species (ROS), and apoptotic signaling pathways. All of the genes were involved/associated with chronic bronchitis, adenocarcinoma of the lung, non-small-cell lung carcinoma, carcinoma, small cell lung carcinoma, type 2 diabetes mellitus, emphysema, ischemic stroke, lung diseases, and inflammation. Thus, AST treatment for smokers could potentially decrease the development of ROS and oxidative stress that leads to inflammation and health risks associated with smoking.

Arachidonic acid (AA) is a key precursor for proinflammatory and anti-inflammatory derivatives that regulate the inflammatory response. The modulation of AA metabolism is a target for searching a therapeutic agent with potent anti-inflammatory action in cardiovascular disorders. Therefore, our study aims to determine the potential preventive impact of N-acetylcysteine (NAC) supplementation on myocardial inflammation and the occurrence of oxidative stress in obesity induced by high-fat feeding. The experiment was conducted for eight weeks on male Wistar rats fed a standard chow or a high-fat diet (HFD) with intragastric NAC supplementation. The Gas-Liquid Chromatography (GLC) method was used to quantify the plasma and myocardial AA levels in the selected lipid fraction. The expression of proteins included in the inflammation pathway was measured by the Western blot technique. The concentrations of arachidonic acid derivatives, cytokines and chemokines, and oxidative stress parameters were determined by the ELISA, colorimetric, and multiplex immunoassay kits. We established that in the left ventricle tissue NAC reduced AA concentration, especially in the phospholipid fraction. NAC administration ameliorated the COX-2 and 5-LOX expression, leading to a decrease in the PGE2 and LTC4 contents, respectively, and augmented the 12/15-LOX expression, increasing the LXA4 content. In obese rats, NAC ameliorated NF-κB expression, inhibiting the secretion of proinflammatory cytokines. NAC also affected the antioxidant levels in HFD rats through an increase in GSH and CAT contents with a simultaneous decrease in the levels of 4-HNE and MDA. We concluded that NAC treatment weakens the NF-κB signaling pathway, limiting the development of myocardial low-grade inflammation, and increasing the antioxidant content that may protect against the development of oxidative stress in rats with obesity induced by an HFD.

Hyaluronic acid (HA), used in a variety of medical applications, is associated in rare instances to long-term adverse effects. Although the aetiology of these events is unknown, a number of hypotheses have been proposed, including low molecular weight of HA (LMW-HA) in the filler products. We hypothesized that cross-linked HA and its degradation products, in a low-grade inflammatory microenvironment, could impact immune responses that could affect cell behaviours in the dermis. Using two different cross-linking technologies VYC-15L and HYC-24L+, and their hyaluronidase-induced degradation products, we observed for nondegraded HA, VYC-15L and HYC-24L+, a moderate and transient increase in IL-1β, TNF-α in M1 macrophages under low-grade inflammatory conditions. Endothelial cells and fibroblasts were preconditioned using inflammatory medium produced by M1 macrophages. 24 h after LMW-HA fragments and HA stimulation, no cytokine was released in these preconditioned cells. To further characterize HA responses, we used a novel in vivo murine model exhibiting a systemic low-grade inflammatory phenotype. The intradermal injection of VYC-15L and its degradation products induced an inflammation and cell infiltration into the skin that was more pronounced than those by HYC-24L+. This acute cutaneous inflammation was likely due to mechanical effects due to filler injection and tissue integration rather than its biological effects on inflammation. VYC-15L and its degradation product potentiated microvascular response to acetylcholine in the presence of a low-grade inflammation. The different responses with 2D cell models and mouse model using the two tested cross-linking HA technologies showed the importance to use integrative complex model to better understand the effects of HA products according to inflammatory state.

Background: Patients with moderate or severe COVID-19 infection suffer from varying levels of fatigue; however, there is a lack of understanding regarding the effect of inflammation on fatigue; and whether these relationships differ according to the severity of the infection.

Aim: To assess the relationships between selected inflammatory biomarkers and fatigue levels among hospitalized Jordanian patients with moderate or severe COVID-19 infection.

Methods: A quantitative cross-sectional design was used. A total of 352 participants were recruited for the study. Data regarding fatigue type and level were collected using the Chalder fatigue scale. Laboratory test results regarding several selected inflammatory biomarkers (e.g., ESR, CRP, IL-6, D-dimer, and others) were collected from patient records. The severity of the COVID-19 infection was determined using the criteria of the Ministry of Health in Jordan based on the results of O₂% (oxygen saturation).

Results: The mean scores of the total fatigue level significantly differed between the two levels of the severity of COVID-19 infection (moderate and severe levels) (t = -3.0, p < 0.05). Similar findings were observed with physiological fatigue (t = -3.50, p < 0.05), and no significant difference was observed in psychological fatigue. Out of the selected inflammatory markers, only neutrophil and lymphocyte count had a significant influence on total fatigue level.

Conclusion: The level and type of fatigue was affected by the severity of the disease. However, the disease process itself represented by the levels of the inflammatory markers showed little influence on fatigue. The implications such as continuous screening of fatigue, and monitoring of the levels of the inflammatory markers are important to assist in diagnosing and managing COVID-19 patients. Furthermore, the relationship between the inflammatory process and fatigue is complex and requires further exploration.

Several key player factors, such as cytokine and complement, play an important role in the pathogenesis of systemic lupus erythematosus (SLE). The purpose of this study was to reveal the association between complement 3 (C3), complement 4 (C4), interleukin-6 (IL-6), and transforming growth factor-β (TGF-β) with SLE disease activity, renal damage, and hematological activity in patients with naïve SLE. The Laboratory of Clinical Pathology Dr. Soetomo General Hospital in Surabaya performed all laboratory examinations on thirty women with naïve SLE. The SLE diagnosis is based on ACR criteria (1998 revised criteria) from Dr. Soetomo General Hospital Surabaya, Indonesia, and the systemic lupus activity measurement (SLAM) score is used to assess the disease activity. The correlation was statistically tested using the Spearman and Pearson tests. The differences in cytokine and complement levels are between SLE severity groups using the two-way Anova and Kruskal-Wallis. The unpaired T-test and Mann-Whitney test were used to determine the differences between the relatively normal and the more severe groups of organ damage and hematological activity. All tests were two-tailed, analyzed with GraphPad Prism 9 for windows, and a p value of less than 0.05 was considered statistically significant. This study found a significant decrease in C3 (20.2, 16.4-24.2 mg/dL) and C4 (7, 6-14.3 mg/dL) and an increase in IL-6 (35.60 ± 7.43 mg/dL) and TGF-β (311.1 ± 290.8 mg/dL) in the group of severe patients with SLAM scores >30. Although there is no significant relationship between SLAM and renal impairment or hematologic activity, patients with higher SLAM had a significant decrease in complement; this complement decrease was also significant in patients with higher leukocyte counts. An insignificant increase in cytokines was also observed in patients with higher SLAM. Patients with high serum creatinine levels had a significant increase in TGF-β, whereas those with a faster ESR had a significant increase in IL-6. In conjunction with complements evaluation, assessment of the cytokine profile may become a promising marker for reliable diagnosis and treatment of SLE in the future.

The incidence of COVID-19 infection and death is known to be lower in tuberculosis (TB) endemic countries than in nonendemic countries. The Bacillus Calmette-Guerin (BCG) vaccination, which is commonly administered in TB endemic countries, was previously reported to have a nonspecific protective effect against several infections, including COVID-19. In this study, we used a differentially expressed genes (DEG) approach to analyze the genes modulated by BCG vaccination and COVID-19 infection. The Gene Expression Omnibus (GEO) database was used to select a COVID-19 gene expression data set with GSE164805, GSE14408, and GSE58636, and DEG in each data set were identified using the GEO2R online tools and selected using the adjusted p value (padj) 0.05 criteria. The protein-protein interaction (PPI) network was constructed from DEGs with the same trend of expression (upregulation or downregulation) using STRING version 11. The PPI network was performed by using the highest confidence number (0.9). DEGs that have a high-trust network were collected and functional cluster analysis of biological processes from Gene Ontology (GO), pathway analysis from the Human KEGG pathway, and COVID-19-related gene analysis was carried out using the Enrichr database. We found that either BCG or tuberculin increased the expression of several genes related to hyperinflammation, such as CCL3, CCL4, CSF2, IL1B, and LTA. In severe COVID-19, these genes were downregulated. This leads to the hypothesis that revaccination may have a protective effect against the severity of COVID-19 by reducing the hyperinflammatory status.

Background: Pharmacotherapy with medicinal plants is a promising approach to treat cancer. Cinnamon is a medicinal plant whose properties have been proven in various fields of medical sciences. Among its biological activities, its antioxidant and antiviral effects can be mentioned. In this study, the antitumor effects of Cinnamon with a focus on glucose metabolism in bladder cancer carcinoma cell-line 5637 were investigated.

Methods: Aqueous extract of Cinnamon was prepared from Cinnamon bark. Bladder cancer 5637cell line were treated with different concentrations of aqueous extract of Cinnamon. MTT was used to evaluate cell viability at 24, 48, and 72 h. The concentration of 1.25, 2.50, and 5 mg/ml was used. Apoptosis was assessed with Hochest33258 staining. For evaluating of aqueous extract of Cinnamon effect on glycolysis, the gene expression of epidermal growth factor receptor 2 (ErbB2), heat shock protein transcription factor1 (HSF1), and lactate dehydrogenase A (LDHA), as well as protein levels of HSF1 and LDHA, LDH activity, glucose consumption, and lactate production, were measured.

Results: Aqueous extract of Cinnamon significantly decreased ErbB2, HSF1, and LDHA gene expression and also decreased the protein level of HSF1 and LDHA, LDH activity, glucose consumption, and lactate production dose-dependently (p < 0.05).

Conclusion: Our finding showed that the aqueous extract of Cinnamon can inhibit proliferation in 5637 cells by inhibition of glycolysis and induction of apoptosis.