Interleukin-10 (IL-10) is an immunoregulatory cytokine that plays a pivotal role in modulating inflammation. IL-10 has inhibitory effects on proinflammatory cytokine production and function in vitro and in vivo; as such, IL-10 is viewed as a potential treatment for various inflammatory diseases. However, a significant drawback of using IL-10 in clinical application is the fact that the biologically active form of IL-10 is an unstable homodimer, which has a short half-life and is easily degraded in vivo. Consequently, IL-10 therapy using recombinant native IL-10 has had only limited success in the treatment of human disease. To improve the therapeutic potential of IL-10, we have generated a novel form of IL-10, which consists of two IL-10 monomer subunits linked in a head to tail fashion by a flexible linker. We show that the linker length per se did not affect the expression and biological activity of the stable IL-10 molecule, which was more active than natural IL-10, both in vitro and in vivo. We confirmed that the new form of IL-10 had a much-improved temperature- and pH-dependent biological stability compared to natural IL-10. The IL-10 dimer protein binds to the IL-10 receptor similarly to the natural IL-10 protein, as shown by antibody blocking and through the genetic modifications of one monomer in the IL-10 dimer specifically at the IL-10 receptor binding site. Finally, we showed that stable IL-10 is more effective at suppressing LPS-induced-inflammation in vivo compared to the natural IL-10. In conclusion, we have developed a new stable dimer version of the IL-10 protein with improved stability and efficacy to suppress inflammation. We propose that this novel stable IL-10 dimer could serve as the basis for the development of targeted anti-inflammatory drugs.

Background: SARS, MERS, and COVID-19 share similar characteristics. For instance, the genetic homology of SARS-CoV-2 compared to SARS-CoV and MERS-CoV is 80% and 50%, respectively, which may cause similar clinical features. Moreover, uncontrolled release of proinflammatory mediators (also called a cytokine storm) by activated immune cells in SARS, MERS, and COVID-19 patients leads to severe phenotype development. Aim: This systematic review and meta-analysis aimed to evaluate the inflammatory cytokine profile associated with three strains of severe human coronavirus diseases (MERS-CoV, SARS-CoV, and SARS-CoV-2). Method: The PubMed, Embase, and Cochrane Library databases were searched for studies published until July 2020. Randomized and observational studies reporting the inflammatory cytokines associated with severe and non-severe human coronavirus diseases, including MERS-CoV, SARS-CoV, and SARS-CoV-2, were included. Two reviewers independently screened articles, extracted data, and assessed the quality of the included studies. Meta-analysis was performed using a random-effects model with a 95% confidence interval to estimate the pooled mean of inflammatory biomarkers. Results: A high level of circulating IL-6 could be associated with the severity of infection of the three coronavirus strains. TNF, IL-10, and IL-8 are associated with the severity of COVID-19. Increased circulating levels of CXCL10/IP10 and CCL2/MCP-1 might also be related to the severity of MERS. Conclusion: This study suggests that the immune response and immunopathology in the three severe human coronavirus strains are somewhat similar. The findings highlight that nearly all studies reporting severe cases of SARS, MERS, and COVID-19 have been associated with elevated levels of IL-6. This could be used as a potential therapeutic target to improve patients’ outcomes in severe cases. Systematic Review Registration: PROSPERO registration 94 number: CRD42020209931.

This study aimed to determine the chemical composition of the essential oils (EOs) of Ocimum basilicum L., as well as to evaluate the antibacterial, antidiabetic, dermatoprotective, and anti-inflammatory properties, and the EOs and aqueous extracts of O. basilicum. The antibacterial activity was evaluated against bacterial strains, Gram-positive and Gram-negative, using the well diffusion and microdilution methods, whereas the antidiabetic activity was assessed in vitro using two enzymes involved in carbohydrate digestion, α-amylase and α-glucosidase. On the other hand, the dermatoprotective and anti-inflammatory activities were studied by testing tyrosinase and lipoxygenase inhibition activity, respectively. The results showed that the chemical composition of O. basilicum EO (OBEO) is dominated by methyl chavicol (86%) and trans-anethol (8%). OBEO exhibited significant antibacterial effects against Gram-negative and Gram-positive strains, demonstrated by considerable diameters of the inhibition zones and lower MIC and MBC values. In addition, OBEO exhibited significant inhibition of α-amylase (IC₅₀ = 50.51 ± 0.32 μg/mL) and α-glucosidase (IC₅₀ = 39.84 ± 1.2 μg/mL). Concerning the anti-inflammatory activity, OBEO significantly inhibited lipoxygenase activity (IC₅₀ = 18.28 ± 0.03 μg/mL) compared to the aqueous extract (IC₅₀ = 24.8 ± 0.01 μg/mL). Moreover, tyrosinase was considerably inhibited by OBEO (IC₅₀ = 68.58 ± 0.03 μg/mL) compared to the aqueous extract (IC₅₀ = 118.37 ± 0.05 μg/mL). The toxicological investigations revealed the safety of O. basilicum in acute and chronic toxicity. The finding of in silico analysis showed that methyl chavicol and trans-anethole (main compounds of OBEO) validate the pharmacokinetics of these compounds and decipher some antibacterial targets.

Interleukin-10 (IL-10) is a dimeric cytokine encoded by the IL-10 gene on chromosome 1

Inflammatory Bowel Diseases (IBD), which encompass ulcerative colitis (UC) and Crohn’s disease (CD), are characterized by chronic inflammation and tissue damage of the gastrointestinal tract. This study aimed to uncover novel disease-gene signatures, dysregulated pathways, and the immune cell infiltration landscape of inflamed tissues. Eight publicly available transcriptomic datasets, including inflamed and non-inflamed tissues from CD and UC patients were analyzed. Common differentially expressed genes (DEGs) were identified through meta-analysis, revealing 180 DEGs. DEGs were implicated in leukocyte transendothelial migration, PI3K-Akt, chemokine, NOD-like receptors, TNF signaling pathways, and pathways in cancer. Protein–protein interaction network and cluster analysis identified 14 central IBD players, which were validated using eight external datasets. Disease module construction using the NeDRex platform identified nine out of 14 disease-associated genes (CYBB, RAC2, GNAI2, ITGA4, CYBA, NCF4, CPT1A, NCF2, and PCK1). Immune infiltration profile assessment revealed a significantly higher degree of infiltration of neutrophils, activated dendritic cells, plasma cells, mast cells (resting/activated), B cells (memory/naïve), regulatory T cells, and M0 and M1 macrophages in inflamed IBD tissue. Collectively, this study identified the immune infiltration profile and nine disease-associated genes as potential modulators of IBD pathogenesis, offering insights into disease molecular mechanisms, and highlighting potential disease modulators and immune cell dynamics.

Background: Large numbers of people infected with COVID-19 developed acute symptoms. Post-COVID-19 conditions have been reported after recovery or discharge from the hospital. However, little is known about the prevalence and possible risk factors of post-COVID-19 conditions in the Saudi community. Here, we describe the incidence of post-COVID-19 conditions among the general population of Saudi Arabia. Methods: We conducted a cross-sectional, nationwide study using an online survey in Saudi Arabia from 1 September 2021 to 28 February 2022. The survey was distributed using social media platforms, such as Twitter, WhatsApp, and Facebook. Patients with SARS-CoV-2 infection were included in the questionnaire adapted from published studies. Result: The study enrolled 7520 individuals who were previously infected with SARS-CoV-2. Most patients in our study were symptomatic and their acute symptoms may persist for more than six days. On the other hand, long-term complications may develop and continue for an extended period (post-COVID-19 conditions). Most of these complications are respiratory, neurological, psychological, or skin related. The proportion of long-term complications reported in this study is 36% among SARS-CoV-2-infected individuals. In addition, being female, old age, number of chronic complications, long-term medication, length of stay in hospital and intensive care unit, and duration of acute symptoms may be significant predictors of post-COVID-19 symptoms. Conclusion: In conclusion, the incidence of post-COVID-19 conditions among the Saudi population was high, which urges further investigation into the risk factors associated with post-COVID-19 symptoms.