Metronidazole, acyclovir and tetrahydrobiopterin may be promising to treat COVID-19 patients, through interaction with interleukin-12.

COVID-19 patients have shown overexpressed serum levels of several pro-inflammatory cytokines, leading to a high mortality rate due to numerous complications. Also, previous studies demonstrated that the metronidazole (MTZ) administration reduced pro-inflammatory cytokines and improved the treatment outcomes for inflammatory disorders. However, the effect and mechanism of action of MTZ on cytokines have not been studied yet. Thus, the current study aimed to identify anti-cytokine therapeutics for the treatment of COVID-19 patients with cytokine storm. The interaction of MTZ with key cytokines was investigated using molecular docking studies. MTZ-analogues, and its structurally similar FDA-approved drugs were also virtually screened against interleukin-12 (IL-12). Moreover, their mechanism of inhibition regarding IL-12 binding to IL-12 receptor was investigated by measuring the change in volume and area. IL-12-metronidazole complex is found to be more stable than all other cytokines under study. Our study also revealed that the active sites of IL-12 are inhibited from binding to its target, IL-12 receptor, by modifying the position of the methyl and hydroxyl functional groups in MTZ. Three MTZ analogues, metronidazole phosphate, metronidazole benzoate, 1-[1-(2-Hydroxyethyl)-5-nitroimidazol-2-yl]-N-methylmethanimine-oxide, and two FDA-approved drugs acyclovir (ACV), and tetrahydrobiopterin (THB) were also found to prevent binding of IL-12 to IL-12 receptor similar to MTZ by changing the surface and volume of IL-12 upon IL-12-drug/ligand complex formation. According to the RMSD results, after 100 ns MD simulations of human IL-12-MTZ/ACV/THB drug complexes, it was also observed that each complex was swinging within a few Å compared to their corresponding docking poses, indicating that the docking poses were reliable. The current study demonstrates that three FDA-approved drugs, namely, metronidazole, acyclovir and tetrahydrobiopterin, are potential repurposable treatment options for overexpressed serum cytokines found in COVID-19 patients. Similar approach is also useful to develop therapeutics against other human disorders.Communicated by Ramaswamy H. Sarma.

The impact of aerosol box on tracheal intubation during the COVID-19 pandemic: a systematic review.

INTRODUCTION: This study aimed to summarize the effect of the aerosol box on tracheal intubation in patients with COVID-19. AREAS COVERED: According to the PRISMA guidelines, a systematic search was performed to identify relevant literature on the 'impact of the aerosol box on tracheal intubation during the COVID-19 pandemic' in different electronic databases up to March 2021. Based on a set of predefined inclusion and exclusion criteria, 447 articles were screened. Finally, 20 articles were included in the current systematic review. The findings showed that the use of aerosol box during intubation could reduce droplet contamination on the healthcare workers but not necessarily aerosols. An increase in the time of intubation with the aerosol box was also observed in 9 out of 12 studies (75%); however, three studies reported no significant difference in the time of intubation with and without the aerosol box. Most studies (8 out of 9, 89%) were also shown that intubation with the aerosol box may lead to more difficulty. EXPERT OPINION: The proceduralist and other healthcare workers involved in airway management of COVID-19 infected patients should decide whether to apply the aerosol box with caution, balancing between benefits and risks, especially in difficult airway circumstances.

The emerging microbiome-based approaches to IBD therapy: From SCFAs to urolithin A.

Inflammatory bowel disease (IBD) is a group of chronic gastrointestinal inflammatory conditions which can be life-threatening, affecting both children and adults. Crohn's disease and ulcerative colitis are the two main forms of IBD. The pathogenesis of IBD is complex and involves genetic background, environmental factors, alteration in gut microbiota, aberrant immune responses (innate and adaptive), and their interactions, all of which provide clues to the identification of innovative diagnostic or prognostic biomarkers and the development of novel treatments. Gut microbiota provide significant benefits to its host, most notably via maintaining immunological homeostasis. Furthermore, changes in gut microbial populations may promote immunological dysregulation, resulting in autoimmune diseases, including IBD. Investigating the interaction between gut microbiota and immune system of the host may lead to a better understanding of the pathophysiology of IBD as well as the development of innovative immune- or microbe-based therapeutics. In this review we summarized the most recent findings on innovative therapeutics for IBD, including microbiome-based therapies such as fecal microbiota transplantation, probiotics, live biotherapeutic products, short-chain fatty acids, bile acids, and urolithin A.

Intimate partner violence against pregnant women during the COVID-19 pandemic: a systematic review and meta-analysis.

This systematic review and meta-analysis aimed to estimate the pooled prevalence of (intimate partner violence) IPV against pregnant women in the COVID-19 pandemic. A literature search was conducted in PubMed, Web of Science, and Scopus for observational studies regarding the prevalence of IPV against pregnant women during the COVID-19 pandemic. The search was performed with the following keywords: intimate partner violence, domestic violence, battered women, wife assault, partner assault, wife abuse, partner abuse, femicide, domestic homicide, pregnancy, gestation, pregnant women, COVID-19, SARS-CoV-2, 2019-nCoV, Coronavirus Disease-19, 2019 Novel Coronavirus, Wuhan Coronavirus, SARS Coronavirus 2, Wuhan Seafood Market Pneumonia Virus. Heterogeneity between the studies was assessed using Cochran's Q test and I2 index. In addition, a random-effects model was used to estimate the prevalence of IPV. Data analysis was performed in Stata software version 16. Six articles met our inclusion criteria, which were conducted on 2213 pregnant women. The pooled prevalence of total IPV was estimated at 22 percent (95 percent Confidence Interval [CI]: 4-40 percent). Moreover, the pooled prevalence of psychological, physical, and sexual violence was reported to be 24 percent (95 percent CI: 13-35 percent), 14 percent (95 percent CI: 7-20 percent), and 6 percent (95 percent CI: 4-9 percent), respectively. Publication bias was significant (P = .01). According to the results, IPV against pregnant women has been relatively prevalent during the COVID-19 pandemic. Therefore, identifying the women who are at the risk of IPV is essential to preventing the consequences of maternal-fetal abuse and designing strategies to facilitate the reporting of violence during pandemics.

The emerging role of microbiota-derived short-chain fatty acids in immunometabolism.

The accumulating evidence revealed that microbiota plays a significant function in training, function, and the induction of host immunity. Once this interaction (immune system-microbiota) works correctly, it enables the production of protective responses against pathogens and keeps the regulatory pathways essential for maintaining tolerance to innocent antigens. This concept of immunity and metabolic activity redefines the realm of immunometabolism, paving the way for innovative therapeutic interventions to modulate immune cells through immune metabolic alterations. A body of evidence suggests that microbiota-derived metabolites, including short-chain fatty acids (SCFAs) such as butyrate, acetate, and propionate, play a key role in immune balance. SCFAs act on many cell types to regulate various vital biological processes, including host metabolism, intestinal function, and the immune system. Such SCFAs generated by gut bacteria also impact immunity, cellular function, and immune cell fate. This is a new concept of immune metabolism, and better knowledge about how lifestyle affects intestinal immunometabolism is crucial for preventing and treating disease. In this review article, we explicitly focus on the function of SCFAs in the metabolism of immune cells, especially macrophages, neutrophils, dendritic cells (DCs), B cells, T (Th) helper cells, and cytotoxic T cells (CTLs).

Does CCL19 act as a double-edged sword in cancer development?

Cancer is considered a life-threatening disease, and several factors are involved in its development. Chemokines are small proteins that physiologically exert pivotal roles in lymphoid and non-lymphoid tissues. The imbalance or dysregulation of chemokines has contributed to the development of several diseases, especially cancer. CCL19 is one of the homeostatic chemokines that is abundantly expressed in the thymus and lymph nodes. This chemokine, which primarily regulates immune cell trafficking, is involved in cancer development. Through the induction of anti-tumor immune responses and inhibition of angiogenesis, CCL19 exerts tumor-suppressive functions. In contrast, CCL19 also acts as a tumor-supportive factor by inducing inflammation, cell growth, and metastasis. Moreover, CCL19 dysregulation in several cancers, including colorectal, breast, pancreatic, and lung cancers, has been considered a tumor biomarker for diagnosis and prognosis. Using CCL19-based therapeutic approaches has also been proposed to overcome cancer development. This review will shed more light on the multifarious function of CCL19 in cancer and elucidate its application in diagnosis, prognosis, and even therapy. It is expected that the study of CCL19 in cancer might be promising to broaden our knowledge of cancer development and might introduce novel approaches in cancer management.