International Journal of Inflammation最新文献

Coronavirus disease-19 (COVID-19) is correlated to a severe condition caused by a cytokine storm during which numerous proinflammatory cytokines, including interleukin-6 (IL-6) are released. IL-6 is a critical driver in the COVID-19 inflammatory state, and the inhibition is considered a potential treatment approach to prevent serious complications. Meanwhile, Melaleuca cajuputi is a plant with antibacterial, antiviral, anti-inflammatory, and antioxidant activities. Therefore, this aimed to investigate the anti-inflammatory potential of M. cajuputi in silico. Extraction of leaves was conducted by using 96% ethanol, followed by fractionation to obtain active compounds. Subsequently, LC/MS and GC/MS analyses were performed to obtain active compound profiling. Protein-protein interaction (PPI), as well as molecular docking and dynamic analyses, were performed to examine interaction of active compounds of M. cajuputi with IL-6. The results showed that 30 protein nodes played a significant role in COVID-19 cytokine storm and eight active compounds had interactions with IL-6. Among the active compounds, pinostrobin chalcone had the best delta G interaction with IL-6. In conclusion, M. cajuputi has potential activity as an anti-inflammatory agent against COVID-19.

Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by inflammation, progressive vasculopathy, and fibrosis of skin and internal organs. The aim of the study was to evaluate extended inflammatory parameters (EIP) in patients with SSc in comparison to the control group of healthy subjects.

Methods: A total of 28 patients with SSc and 29 healthy controls (HCs) were included in the study. The following EIP parameters were analyzed: neutrophil reactive intensity (NEUT-RI), neutrophil granularity intensity (NEUT-GI), antibody-synthesizing lymphocytes (AS-LYMP), and reactive lymphocytes (RE-LYMP).

Results: Patients with SSc showed significantly higher values of parameters determining neutrophil reactivity and neutrophil granularity when compared to HCs (respectively, 49.16 FI vs. 44.33 FI, p < 0.001, and 152.01 SI vs. 147.51 SI, p < 0.001). Moreover, patients with SSc had higher absolute numbers of RE-LYMP than HCs (0.69 × 10³/µl vs. 0.04 × 10³/µl, p < 0.001). Importantly, significant correlations between the RE-LYMP and either IL-6 (R = 0.447, p < 0.001) or ESR (R = 0.532, p < 0.001) were found among patients with SSc.

Conclusions: Changes in NEUT-RI, NEUT-GI, and RE-LYMP levels positively correlate with inflammation in SSc and, thus, could potentially be used as an additional reliable inflammatory biomarker to assess inflammation in this disease.

The hypothalamic-pituitary-somatotropic (HPS) axis controls many physiological and pathophysiological processes. The phenomenon of insensitivity to growth hormone resistance (GHres) was previously reported to be due to the development of inflammation. Therefore, the primary aim of the study was to determine the impact of inflammation caused by lipopolysaccharides (LPS) on the secretory activity of the HPS axis in sheep. The further goal was to determine the effect of inflammatory factors on individual components involved in intracellular signal transduction to GH via the GH receptor (GHR). The research was carried out on 24 seasonal sheep kept under a short-day photoperiod, randomly divided into two groups. Before the experiment, the sheep estrous cycles were synchronized. The results of the current study in a sheep model showed that inflammation impairs the activity of the somatotropic axis. On the one hand, LPS injection stimulated (p < 0.01) GH secretion, and on the other hand, it reduced the liver's sensitivity to this hormone by directly reducing (p < 0.01) GHR expression and activating the GHR inhibitory signal transduction mechanism. A symptom of such an inhibitory postreceptor signaling pathway may be due to an increase in SOCS3 expression (p < 0.01). The effect of various inhibition pathways is a significant reduction in the expression of the main transcription activator IGF1-STAT5B (p < 0.05). The action of GHres in the liver resulted in the inhibition of IGF1 secretion, which in the long term may have negative consequences for growth and development. Our study suggests that disruption of the GH cell signaling pathway may be one of the important elements of the pathophysiology of inflammation. It can suppress growth and hepatic metabolism to spare energy expenditure.

Inflammatory and antimicrobial diseases constitute a major burden for society, and fighting them is a WHO strategic priority. Most of the treatments available to fight inflammatory diseases are anti-inflammatory drugs, such as corticosteroids or immunomodulators that lack cellular specificity and lead to numerous side effects. In addition to suppressing undesired inflammation and reducing disease progression, these drugs lessen the immune system protective functions. Furthermore, treating infectious diseases is more and more challenging due to the rise of microbial resistance to antimicrobial drugs. Thus, controlling the inflammatory process locally without compromising the ability to combat infections is an essential feature in the treatment of inflammatory diseases. We isolated three forms (DRS-DA2N, DRS-DA2NE, and DRS-DA2NEQ) of the same peptide, DRS-DA2, which belongs to the dermaseptin family, from the Mexican tree frog Pachymedusa dacnicolor. Interestingly, DRS-DA2N and DRS-DA2NEQ exhibit a dual activity by inducing the death of leukocytes as well as that of Gram-negative and Gram-positive bacteria, including multiresistant strains, without affecting other cells such as epithelial cells or erythrocytes. We showed that the death of both immune cells and bacteria is induced rapidly by DRS-DA2 and that the membrane is permeabilized, leading to the loss of membrane integrity. We also validated the capacity of DRS-DA2 to regulate the pool of inflammatory cells in vivo in a mouse model of noninfectious peritonitis. After the induction of peritonitis, a local injection of DRS-DA2N could decrease the number of inflammatory cells locally in the peritoneal cavity without inducing a systemic effect, as no changes in the number of inflammatory cells could be detected in blood or in the bone marrow. Collectively, these data suggest that this peptide could be a promising tool in the treatment of inflammatory diseases, such as inflammatory skin diseases, as it could reduce the number of inflammatory cells locally without suppressing the ability to combat infections.

Materials and methods: 130 subjects were enrolled in a case-control study at two tertiary university hospitals from Tabriz (Imam and Razi), Iran. Of these, 65 subjects were MS patients serving as the case group, and 65 subjects were healthy individuals serving as the control group. After DNA extraction from all samples, the EBER region of EBV genome was used as the primer for the detection of EBV. RNA was extracted from PBMCs, and cDNA synthesis was performed by using Sina Gene kit. Subsequently, each sample was analysed by RT-PCR with two sets of primers to detect specifically multiple sclerosis retroviruses (MSRV) env, and RT-PCR was repeated for each HERV-W env. Positive sample was used in order to confirm the result.

Results: In the case group, 19 (29.2%) patients were male and 46 (70.8%) patients were female. Nevertheless, in the control group, 21 (32.3%) subjects were male and 44 (67.7%) subjects were female. No significant difference was found between groups in gender (p = 0.70). The mean range in control and case groups was 33/38 ± 9/85 and 33.18 ± 8.65, respectively. No significant difference was found between groups in age (p = 0.902). 4 (6.2%) patients in case groups were found to be positive for EBV DNA (p = 0.119). Expression of the env gene of HERVs was observed in 10 (15.38%) and two (3.07%) specimens in the case and control groups (p = 0.030), separately. A comparison of the prevalence of the HERV ENV genome between the two study groups showed a significant difference (p = 0.005).

Conclusion: The results of this study failed to show any difference between MS patients and healthy controls in the rate of EBV infection. It can be concluded that the expression of HERV-W/env genes may be involved in the development of MS in these patients.

Background: Overweight and obesity are global health issues, impacting a significant portion of young adults. Obesity is a complex condition influenced by genetics and environmental factors, leading to increased susceptibility to cardiovascular diseases (CVDs), hypertension, dyslipidemia, and insulin resistance. Irisin, a protein derived from the cleavage of fibronectin type III domain-containing protein 5, may have relationship with these cardiometabolic diseases.

Objective: This systematic review aims to examine the relationship between serum irisin levels and obesity, particularly in individuals predisposed to cardiovascular risk factors.

Methods: A thorough literature search was conducted in multiple databases, including "Science Direct," "Scopus," "PubMed," and "Lilacs," from July 2020. Inclusion criteria encompassed subjects with metabolic disorders (with or without obesity, BMI ≥30 kg/m²), clinical trials, and observational studies published between 2010 and June 2020. Exclusion criteria were animal studies, meta-analyses, systematic reviews, studies evaluating only healthy subjects, and those investigating disorders beyond cardiometabolic diseases.

Results: Out of 151 identified articles, 30 met the inclusion criteria. These studies, published between 2013 and 2020, assessed adults (≥21 years) and included 26 observational studies and 4 clinical trials (n = 7585 subjects). All studies examined irisin's role in obesity and CVDs, often including associated diseases such as type 2 diabetes and hypertension. Despite varying sample sizes, the samples within the articles were homogeneous. Observational studies exhibited a low risk of bias in at least 60% of the evaluated domains. Clinical trials demonstrated a low risk of bias in at least 50% of the domains. Limitations. Although the systematic review provides valuable insights, it is limited by the available literature and the varying methodologies used across studies.

Conclusion: The review suggests that irisin plays a significant role as both a preventive measure and a biomarker for comorbidities linked to obesity and cardiometabolic disorders. Future research should focus on standardized irisin measurement methods and diverse populations to further elucidate its mechanisms of action.

Background: Hyperactivation of protein tyrosine phosphatase (PTP1B) has been associated with several metabolic malfunctions ranging from insulin resistance, metaflammation, lipotoxicity, and hyperglycaemia. Liver metabolism failure has been proposed as a core element in underlying endocrine disorders through persistent inflammation and highly fibrotic phenotype.

Methods: In this study, the outcomes of PTP1B inhibition using trodusquemine (MSI-1436) on key equine metabolic syndrome (EMS)-related alterations including inflammation, fibrosis, and glucose uptake have been analyzed in liver explants collected from EMS-affected horses using various analytical techniques, namely, flow cytometry, RT-qPCR, and Western blot.

Results: PTP1B inhibition using trodusquemine resulted in decreased proinflammatory cytokines (IL-1β, TNF-α, and IL-6) release from liver and PBMC affected by EMS and regulated expression of major proinflammatory microRNAs such as miR-802 and miR-211. Moreover, MSI-1436 enhanced the anti-inflammatory profile of livers by elevating the expression of IL-10 and IL-4 and activating CD4⁺CD25⁺Foxp3⁺ regulatory T cells in treated PBMC. Similarly, the inhibitor attenuated fibrogenic pathways in the liver by downregulating TGF-β/NOX1/4 axis and associated MMP-2/9 overactivation. Interestingly, PTP1B inhibition ameliorated the expression of TIMP-1 and Smad7, both important antifibrotic mediators. Furthermore, application of MSI-1436 was found to augment the abundance of glycosylated Glut-2, which subsequently expanded the glucose absorption in the EMS liver, probably due to an enhanced Glut-2 stability and half-life onto the plasma cell membranes.

Conclusion: Taken together, the presented data suggest that the PTP1B inhibition strategy and the use of its specific inhibitor MSI-1436 represents a promising option for the improvement of liver tissue integrity and homeostasis in the course of EMS and adds more insights for ongoing clinical trials for human MetS management.

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.