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Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease and bronchiolitis in children, as well as an important cause of morbidity and mortality in elderly and immunocompromised individuals. However, there is no safe and efficacious RSV vaccine or antiviral treatment. Toll Like Receptors (TLR) are important molecular mediators linking innate and adaptive immunity, and their stimulation by cognate agonists has been explored as antiviral agents. Imiquimod is known as a TLR7 agonist, but additionally acts as an antagonist for adenosine receptors. In this study, we demonstrate that imiquimod, but not resiquimod, has direct anti-RSV activity via PKA pathway in HEp-2 and A549 cells, independently of an innate response. Imiquimod restricts RSV infection after viral entry into the host cell, interfering with viral RNA and protein synthesis. Probably as a consequence of these anti-RSV properties, imiquimod displays cytokine modulating activity in RSV infected epithelial cells. Moreover, in a murine model of RSV infection, imiquimod treatment improves the course of acute disease, evidenced by decreased weight loss, reduced RSV lung titers, and attenuated airway inflammation. Consequently, imiquimod represents a promising therapeutic alternative against RSV infection and may inform the development of novel therapeutic targets to control RSV pathogenesis., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Based on aroeira's (Myracrodruon urundeuva) antimicrobial activity and a future trend to compose intracanal medication, the aim of this study was to assess in vivo inflamatory tissue response to the extracts by edemogenic and histological analysis containing inactivated facultative and anaerobic microorganisms. For edema quantification, eighteen animals were divided into three groups (n = 3, periods: 3 and 6 hours) and 0.2 mL of 1% Evans blue per 100 g of body weight was injected into the penile vein under general anesthesia. After 30 min the animals received a subcutaneous injection in the dorsal region of aqueous or ethanolic extract of aroeira or saline (control) containing inactivated bacteria. Samples were collected, immersed in formamide for 72h, and evaluated by spectrophotometry (630 m). For histological analysis, polyethylene tubes with the extracts were implanted in the dorsal of 30 male rats. Analysis of the fibrous capsule and inflammatory infiltrate were performed after 7 and 30 days. The aqueous extract group induced less edema in both postoperative periods compared to the other groups, but the differences were not significant (p > 0.05). Tissue repair was significantly better after 30 days than after 7 days (p < 0.01). The aqueous solution showed less inflammatory response than the ethanolic solution (p < 0.05), with tendency for better results than control after 7 days. After 30 days, the response to both extracts was similar to control. The aqueous and ethanolic aroeira extracts containing inactivated microorganisms showed a trend for better results than saline, even when associated with microorganisms, and facilitated the tissue repair process.

Objective: To evaluate the effects of cigarette smoke inhalation on the immune‐inflammatory profile of experimental apical periodontitis in rats. Methodology: In total, 32 male Wistar rats were divided into four groups (n = 8): AP—induced apical periodontitis; S—cigarette smoke inhalation; APS—induced AP and cigarette smoke inhalation; and C (control)—neither AP nor cigarette smoke inhalation. To induce cigarette smoke inhalation, the animals were kept in a chamber filled with tobacco smoke for 8 min thrice a day for 50 days. AP was induced 20 days after inhalation initiation by exposing their coronary pulp to their oral environment for 30 days. After animals were euthanized, their right hemimaxillae were removed for histopathological, semi‐quantitative and immunohistochemical (F4/80, CD206 and iNOS) analyses. Results: Quantitative data showed a moderate number of inflammatory infiltrates in AP and an intense number in APS (p <.05). Comparing F4/80+ cells showed no statistically significant differences among groups, but we found more CD206+ cells in AP than in C and S (p >.05). INOS+ immunostaining showed a significant increase in AP and APS, when compared with C and S (p <.05). APS had more iNOS+ cells than AP (p <.05). Conclusion: Cigarette smoke inhalation worsened AP, leading to a predominantly pro‐ inflammatory profile in our experimental model. [ABSTRACT FROM AUTHOR]

Biocompatibility and biomineralization of root canal dressings are important requirements for periapical healing. This study evaluated the inflammatory response, biomineralization and tissue repair by collagen fiber maturation in the subcutaneous tissue of rats. Eighteen Wistar rats (n = 6) received subcutaneous implants: calcium hydroxide + propylene glycol [CH+P], calcium hydroxide + propylene glycol + iodoform [CH+P+I], iodoform + carbowax [I+Cwax] and carbowax [Cwax]. Extra empty tubes were used as a control [C]. After 7, 15 and 30 days, the implants were removed with surrounding tissue for staining of hematoxylin-eosin, Von Kossa, picrosirius red and without staining for analysis under polarized light. Results were analyzed via Kruskal–Wallis followed by Dunn testing for nonparametric data and ANOVA followed by a Tukey post hoc test for parametric data (p < 5%). At 7 days, all groups showed a moderate inflammatory reaction and thick fibrous capsule, except the [Cwax] group, with a severe inflammatory infiltrate (p < 0.05). After 15 days, all groups but control had a decrease in inflammatory response. At 30 days, all groups presented a mild reaction and thin fibrous capsule (p > 0.05). Only groups containing calcium hydroxide were found to be positive using Von Kossa staining and polarized light in all periods. At 7 days, all groups showed a higher proportion of immature fibers. At 15 days, the [CH+P] and [Cwax] groups increased their proportion of mature/immature fibers. At 30 days, only the [CH+P] group presented a significant prevalence of mature collagen fibers (p < 0.05). All groups showed biocompatibility, but only groups containing calcium hydroxide induced biomineralization. The addition of iodoform delayed tissue healing. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to evaluate the effects of cigarette smoke inhalation (CSI) on inflammation, pro‐inflammatory mediators and haematological parameters in rats with induced apical periodontitis (AP). Methodology: Thirty‐two 3‐month‐old male Wistar rats were divided into four experimental groups (n = 8): C—Control; S—rats with CSI; AP—rats with AP; and SAP—rats with CSI + AP. Animals in groups S and SAP inhaled cigarette smoke by remaining inside a smoking chamber for 8 min, three times daily, for 50 days. After 20 days of smoke inhalation, animals in AP and SAP groups had the pulps of the lower right first molar exposed to oral environment for 30 days to induce AP. In these subsequent 30 days, animals in group S and SAP continued with CSI. On Day 50, animals were euthanized and mandibles were histologically processed to assess inflammatory infiltrate, immunohistochemical interleukins (IL‐1β, IL‐6 and TNF‐α), and blood samples collected for laboratory analysis. The Mann–Whitney test was performed for non‐parametric data and the pairwise analyses of Student's t‐test for parametric data, with a significance level of p <.050. Results: Inflammatory infiltrate was moderate in AP group and more severe in the SAP (p =.010). The interleukins IL‐6, IL‐1β and TNF‐α were higher in SAP group (p <.001) when compared to the AP group. A greater number of red blood cells (p =.010), haemoglobin (p =.007) and neutrophils (p =.014) were observed in the SAP group in comparison with the AP group. Conclusion: Cigarette smoke inhalation induced a more severe inflammatory infiltrate, with increased levels of pro‐inflammatory cytokines and changes in haematological parameters in rats with induced AP. Thus, CSI aggravated AP, exacerbating the inflammatory response. [ABSTRACT FROM AUTHOR]

Objectives: β‐Escin, one of the constituents of Aesculus hippocastanum L. (Hippocastanaceae) seed extract (AH), inhibits NF‐κB activation, which plays an important role in HSV‐1 replication. The aim was to examine the antiherpetic activity of β‐escin and AH, as well as their effect on the activation of NF‐κB and AP‐1 and cytokine secretion in epithelial cells and macrophages. Methods: Cell viability was evaluated using MTT assay, and antiviral and virucidal activity was determined by plaque assay. The effect on NF‐κB and AP‐1 signalling pathways activation was determined by a luciferase reporter assay, and cytokine production was measured by ELISA. Key findings: β‐Escin and AH had virucidal and anti‐HSV‐1 activities, and the antiviral activity was discovered for other enveloped viruses (VSV and Dengue). Moreover, β‐escin and AH significantly reduced NF‐κB and AP‐1 activation and cytokine production in macrophages stimulated with HSV‐1 and TLRs ligands. However, an enhanced activation of these pathways and an increase in the levels of pro‐inflammatory cytokines in β‐escin and AH‐treated HSV‐1‐infected epithelial cells were found. Conclusions: This study demonstrates virucidal and broad‐spectrum antiviral activities for β escin and AH. Besides, β‐escin and AH modulate cytokine production depending on the stimuli (viral or non‐viral) and the cell type under study. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate edemogenic activity and subcutaneous inflammatory reaction induced by Psidium cattleianum leaf extracts associated with Ca(OH)2. Thirty male Wistar rats, split equally into three groups [aqueous extract + Ca(OH)2; ethanolic extract + Ca(OH)2; and propylene glycol + Ca(OH)2], were assessed every 3 h or 6 h (five animals in each period). Under general anesthesia, 0.2 mL of 1% Evans blue per 100 g of body weight was injected into the penile vein and each combination to be evaluated was subcutaneously injected into the dorsal region 30 min thereafter. Edemogenic activity was analyzed by spectrophotometry (λ=630 nm). For inflammatory reaction analysis, 50 rats received four polyethylene tubes (three experimental groups) and an empty tube (control group). The assessments were made at 7, 15, 30, 60, and 90 days, followed by hematoxylin-eosin staining and by the assignment of scores for evaluation of tissue response intensity. Ethanolic extract + Ca(OH)2 yielded the largest edemogenic activity at 3 h. Intergroup differences at 6 h were not significant. The histological analysis showed progressive repair over time (p<0.05) and aqueous and ethanolic extracts produced similar responses to those of the control and Ca(OH)2 + propylene glycol groups. Psidium cattleianum leaf extracts used as Ca(OH)2 vehicles evoked similar tissue response when compared to Ca(OH)2 associated with propylene glycol. [ABSTRACT FROM AUTHOR]

Obturation of the root canal system aims to fill empty spaces, promoting hermetic sealing and preventing bacterial activity in periapical tissues. This should provide optimal conditions for repair, stimulating the process of biomineralization. An endodontic sealer should be biocompatible once it is in direct contact with periapical tissues. The aim of this study was to evaluate the rat subcutaneous tissue response to implanted polyethylene tubes filled with Smartpaste Bio, Acroseal, and Sealapex and investigate mineralization ability of these endodontic sealers. Forty Wistar rats were assigned to the three sealers groups and control group, (n = 10 animals/group) and received subcutaneous implants containing the test sealers, and the control group were implanted with empty tubes. After days 7, 15, 30, and 60, animals were euthanized and polyethylene tubes were removed with the surrounding tissues. Inflammatory infiltrate and thickness of the fibrous capsule were histologically evaluated. Mineralization was analyzed by Von Kossa staining and polarized light. Data were tabulated and analyzed via Kruskal-Wallis and Dunn's test. All tested materials induced a moderate inflammatory reaction in the initial periods. Smartpaste Bio induced the mildest inflammatory reactions after day 15. No difference was observed among groups after days 30 or 60. Von Kossa-positive staining and birefringent structures observed under polarized light revealed a larger mineralization area in Sealapex-treated animals followed by Smartpaste Bio-treated animals. At the end of the experiment, all tested sealers were found to be biocompatible. All sealers induced biomineralization, except Acroseal, which induced a mild tissue reaction. [ABSTRACT FROM AUTHOR]

Abstract: Meliacine (MA), an antiviral principle present in partially purified leaf extracts of Melia azedarach L., reduces viral load and abolishes the inflammatory reaction and neovascularization during the development of herpetic stromal keratitis in mice. 1-cinnamoyl-3,11-dihydroxymeliacarpin (CDM), obtained from MA, displays anti-herpetic and immunomodulatory activities in vitro. We investigated whether CDM interferes with the angiogenic process. CDM impeded VEGF transcription in LPS-stimulated and HSV-1-infected cells. It proved to have neither cytotoxic nor antiproliferative effect in HUVEC and to restrain HUVEC migration and formation of capillary-like tubes. Moreover, MA inhibits LMM3 tumor-induced neovascularization in vivo. We postulate that the antiangiogenic activity of CDM displayed in vitro as a consequence of their immunomodulatory properties is responsible for the antiangiogenic activity of MA in vivo, which would be associated with the lack of neovascularization in murine HSV-1-induced ocular disease. [Copyright &y& Elsevier]

Although human adenovirus (ADV) infections are mild and self-limited in immunocompetent individuals, they can be severe and life-threatening in immunocompromised patients. Despite their significant clinical impact, there are not currently approved antiviral therapies for ADV infections. On the other hand, in some cases, the immune response induced by ADV infection can cause tissue damage. Even more, in the case of adenovirus vectors used in gene therapy, host immunity generally antagonize viral efficacy. Therefore, the need for searching an effective and safe therapy is increasing. In this work, we describe the antiadenoviral activity of the synthetic stigmastane (22S, 23S)-22,23-dihydroxystigmast-4-en-3-one (Compound 1) with already reported antiviral and antiinflammatory activities against other viruses of clinical importance. Compound 1 displayed no virucidal activity and did not affect ADV entry to the cells. The compound inhibited viral replication and it also reduced cytokine secretion in epithelial and inflammatory infected cells. Thus, Compound 1 would be a promissory drug potentially useful against adenoviral infections as well as an adjuvant of adenoviral vectors in gene therapy. • (22S, 23S)-22,23-dihydroxystigmast-4-en-3-one (Compound 1) displays antiviral activity against Adenovirus. • The compound has no virucidal activity and does not affect virus entry to the cells. • Compound 1 affects early and late stages of virus multiplication cycle. • The antiadenoviral activity of Compound 1 is probably exerted through the inhibition of the AP-1 transcription factor. • Compound 1 reduces cytokine secretion in infected epithelial and inflammatory cells. [ABSTRACT FROM AUTHOR]