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 A549cells. 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).

Background. Colorectal cancer (CRC) is a malignancy derived from the glandular epithelial cells in the colon. Patients with inflammatory bowel disease (IBD) are more likely to develop CRC. Cancer proliferation is characterized by the loss of inhibition of apoptosis, which involves caspase-3 activation. This study examined the effects of the pomegranate peel extract on the expression of caspase-3 in mice crypt cells induced by dextran sodium sulfate (DSS) 2. Methods. The experimental study was done in six groups. All treatments were done in 42 days. The groups were all induced by DSS through water drinking, except for the normal group, which was only given water. The treatments given included the pomegranate extract in two doses (240mg and 480mg/kg bw/day), aspirin, and ellagic acid. The specimens were then fixated and stained for the immunohistochemistry scoring for the expression of caspase-3, which was then analyzed statistically. Results. The H-scores of each treatment group were 213.23±8.32 (DSS group), 243.81±18.69 (normal group), 226.10±12.38 (pomegranate peel extract of 240mg/kg/d), 238.84±15.81 (pomegranate peel extract of 480mg/kg/d), 227.47±12.15 (aspirin), and 224.01±18.39 (ellagic acid). Statistical differences were found in one-way analysis of variance (ANOVA) and post hoc analysis among the DSS group, normal group, and dose 2 group (pomegranate peel extract of 480mg/kg/day). Conclusions. The ethanol extract of pomegranate was able to induce apoptosis, which was demonstrated by the increase of caspase-3 expression.

The development of a tumor has a strong relationship with cellular immunity mediated by T lymphocytes. Some research showed that mangiferin can increase host immunity but its scientific base was still unclear. The purpose of this study was to explain the role of mangiferin as an immunostimulator on in vitro T lymphocytes culture of mammary tumor bearing mice. T lymphocytes were isolated from the spleen of mice after two weeks of mammary tumor transplantation. The isolation was performed by using sterile nylon net and passed through nylon wool. Isolated T lymphocytes were cultured in vitro on RPMI 1640 medium. The culture of T lymphocytes was divided into three groups containing 5, 25 and 50 mg/L of mangiferin, and a control group (RPMI medium). The proportion of T lymphocytes and IL-2Rα (CD25) expressed T cells were evaluated using immunoflouorescens techniques after one and three days of lymphocytes cultures. Our study showed that 5, 25 and 50 mg/L mangiferin was effective to enhance IL-2Rα (CD25) on T lymphocytes culture and T lymphocytes prolifferation.

Introduction. The severity of coronavirus disease 2019 (COVID-19) was known to be affected by hyperinflammation. Identification of important proteins associated with hyperinflammation is critical. These proteins can be a potential target either as biomarkers or targets in drug discovery. Therefore, we combined enrichment analysis of these proteins to identify biological knowledge related to hyperinflammation. Moreover, we conducted transcriptomic data analysis to reveal genes contributing to disease severity. Methods. We performed large-scale gene function analyses using gene ontology to identify significantly enriched biological processes, molecular functions, and cellular components associated with our proteins. One of the appropriate methods to functionally group large-scale protein-protein interaction (PPI) data into small-scale clusters is fuzzy K-partite clustering. We collected the transcriptomics data from GEO Database (GSE 164805 and GPL26963 platform). Moreover, we created a data set and analyzed gene expression using Orange Data-mining version 3.30. PPI analysis was performed using the STRING database with a confidence score >0.9. Results. This study indicated that four proteins were associated with 25 molecular functions, three were associated with 22 cellular components, and one was associated with ten biological processes. All GOs of molecular function, cellular components, and 9 of 14 biological processes were associated with important cytokines related to the COVID-19 cytokine storm present in the resulting cluster. The expression analysis showed the interferon-related genes IFNAR1, IFI6, IFIT1, and IFIT3 were significant genes, whereas PPIs showed their interactions were closely related. Conclusion. A combination of enrichment using GOs and transcriptomic analysis showed that hyperinflammation and severity of COVID-19 may be caused by interferon signaling.

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 ( ) 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.