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Introduction: Drugs that block the renin-angiotensin system (RAS) are widely used for treating hypertension, heart and kidney failure, and the harmful effects of diabetes. Components of the RAS have been identified in various organs, but little is known of their effects on bone remodeling. The aim of this study was to evaluate whether the blockage of the RAS influences strain-induced bone remodeling in a model of orthodontic tooth movement.Methods: An orthodontic appliance was placed in C57BL6/J mice that were randomly divided into 2 groups: vehicle-treated mice (VH) and mice treated with losartan (an angiotensin II receptor blocker). Orthodontic tooth movement and the number of tartrate-resistant acid phosphatase-positive cells were determined by histopathologic analysis. The expression of mediators involved in bone remodeling was evaluated by quantitative real-time polymerase chain reaction. Blood pressure was measured before and during the experimental period.Results: Orthodontic tooth movement and tartrate-resistant acid phosphatase-positive cells were significantly reduced in the losartan group compared with the VH group. mRNA levels of osteoclast markers (RANK, RANKL, cathepsin K, and metalloproteinase 13) were lower in the losartan mice than in the VH group, whereas the expressions of osteoblast markers and negative regulators of bone resorption (periostin, dentin matrix protein, alkaline phosphatase, collagen 1A1, semaphorin 3A3, metalloproteinase 2, and osteoprotegerin) were higher in the VH group.Conclusions: Blockage of the RAS system decreases osteoclast differentiation and activity and, consequently, results in decreased strain-induced bone remodeling in orthodontic tooth movement. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to compare the salivary epidermal growth factor (EGF) levels between patients with oral leukoplakia (OL) and clinically healthy individuals, to evaluate the association between salivary and tissular EGF, and to correlate EGF with clinicopathologic data, including the presence of dysplasia. Study Design Salivary EGF levels were measured in 32 patients and 32 controls. The tissue expressions of EGF and its receptor (EGFR) were immunohistochemically evaluated. Results Salivary EGF levels were similar in patients with OL compared with controls. There was no association between the salivary levels and immunohistochemical expression of EGF. An absence of EGF detection by immunohistochemistry was associated with development of multiple lesions. Dysplastic lesions showed a tendency toward presenting higher salivary EGF levels. Conclusions Currently, it is not possible to indicate salivary EGF as a biomarker for OL. Further studies are needed to elucidate the role of EGF in oral carcinogenesis. A follow-up study is necessary to evaluate the changes in EGF values following the surgical excision of OL. [ABSTRACT FROM AUTHOR]

Evaluate the effects of smoking on dendritic cells (DCs), cytokines, clinical periodontal parameters, and number of teeth in samples of human chronic periodontitis (CP). [ABSTRACT FROM AUTHOR]

Abstract: Aim: Evaluate the effects of smoking on chemokines of the human chronic periodontitis (CP). Materials and methods: Gingival samples were obtained from 23 smokers (S) and 20 non-smokers (NS) diagnosed with CP. Periodontal examination was performed. The CCL2, CCL3, CCL5, CCL19, CCL20, and CXCL8 chemokine levels were measured in gingival tissues using enzyme-linked immunosorbent assay. Chemokines were compared between S and NS, and were correlated with the number of cigarettes per day (C/day) and time of the smoking habit in years (SH/years). Results: CCL3 and CXCL8 of S were significantly smaller than that found in NS subjects, whereas the CCL5 levels increased in the S group. Negative correlations could be observed between CCL19 levels and SH/year. Conclusion: Smoking suppresses the immune response which may contribute to an increased susceptibility to periodontal disease in smokers. [Copyright &y& Elsevier]

Abstract: Periodontal disease (PD) is a chronic inflammatory and alveolar bone destructive disease triggered by microorganisms from the oral biofilm. Oral inoculation of mice with the periodontopathogen Aggregatibacter actinomycetemcomitans (Aa) induces marked alveolar bone loss and local production of inflammatory mediators, including Macrophage Migration Inhibitory Factor (MIF). The role of MIF for alveolar bone resorption during PD is not known. In the present study, experimental PD was induced in BALB/c wild-type mice (WT) and MIF knockout mice (MIF−/−) through oral inoculation of Aa. Despite enhanced number of bacteria, MIF−/− mice had reduced infiltration of TRAP-positive cells and reduced alveolar bone loss. This was associated with decreased neutrophil accumulation and increased levels of IL-10 in periodontal tissues. TNF-α production was similar in both groups. In vitro, LPS from Aa enhanced osteoclastic activity in a MIF-dependent manner. In conclusion, MIF has role in controlling bacterial growth in the context of PD but contributes more significantly to the progression of bone loss during PD by directly affecting differentiation and activity of osteoclasts. [Copyright &y& Elsevier]

Abstract: Objective: The beneficial effects of kappa opioid agonist U-50,488 in preventing periodontal disease (PD) progression in rats have already been described, but its mechanism of action is unknown. The present study evaluated the expression of TNF-α, IL-6, IL-8 and IL-10 in the gingival tissues of rats with ligature-induced PD, treated with U-50,488. It also correlated the effects of this agonist with myeloperoxidase (MPO) activity and the presence of osteoclasts. Design: Male Holtzman rats weighing 250–300g were divided into four groups: (1) control, (2) ligature, (3) ligature+saline and (4) ligature+kappa agonist. Experimental PD was induced by placing a sterile silk ligature around the 2nd left upper molar. Rats from groups 3 to 4 were locally administered with either saline or U-50,488, respectively, from day 3 to day 5 following ligation. After 5 or 11 days, the rats were euthanized and periodontal tissue samples were collected for histological and morphometric analysis and for determination of TNF-α, IL-6, IL-8, IL-10 and MPO. Results: Ligature placement induced significant alveolar bone loss. The number of osteoclasts, degree of MPO activity, IL-6, IL-8 and TNF-α expression were also increased by PD. U-50,488 reduced both bone loss and the number of osteoclasts, but did not alter histological inflammatory infiltrate or MPO activity. U-50,488 significantly reduced IL-6 and increased IL-10 levels, but did not affect TNF-α and IL-8. Conclusion: Lowering the levels of IL-6 and increasing IL-10 are important mechanisms by which U-50,488 reduces alveolar bone loss in ligature-induced periodontal disease. [Copyright &y& Elsevier]

Summary: Objective: A surgical variation of the technique of facial translocation procedure is proposed, which has been called midfacial translocation for approach to the entire medial and lateral region of the middle third of the face, including the rhinopharynx, sphenoid sinus, pterygomaxillary fossa, odontoid process, and clivus. Patients and methods: The medical records of five treated patients accordingly were reviewed for an analysis of the surgical technique, the disease, the topography of the lesion, and the complications. Results: The approach permitted ventral decompression of the bulbomedullary junction with resection of the C1 arch and the odontoid process in four patients and resection of a chordoma of the clivus located along the midline and extending intradurally in the fifth patient. Only one patient presented with dehiscence of the posterior half of the soft palate, this being the only complication observed following surgery in these patients. Three months postoperatively, no patient presented any aesthetic alteration of the face. Functionally, there was only infraorbital hypoaesthesia on the side of flap rotation. Conclusion: The technique of midfacial translocation provides both good surgical approach and access to the rhinopharynx, pterygomaxillary fossa, high odontoid process and clivus, with few adverse sequelae for the patient. [Copyright &y& Elsevier]

Abstract: Central mucoepidermoid carcinoma is a rare mandibular neoplasm. The objective of this paper was to report two cases. [Copyright &y& Elsevier]

• Endogenous opioid system is a player in alveolar bone turnover. • Kappa opioid receptors activation might contribute to decrease alveolar bone loss. • Inhibition of Kappa opioid receptors increases osteoclast number in alveolar bone. Bone resorption associated to chronic diseases, such as arthritis and periodontitis, results from exacerbated immuno-inflammatory host response that leads to tissue breakdown. The significance of opioid pathways as endogenous modulators of inflammatory events has already been described. Thus, the aim of this work is to determine whether some of the main three opioid receptors are endogenously activated to prevent bone loss during experimentally-induced alveolar bone resorption. This study used an experimental model of alveolar bone resorption induced by ligature in rats. A silk thread was placed around the 2nd maxillary molar of male Wistar rats. In the 3rd, 4th and 5th day after ligation the rats received a local injection of different concentrations of opioid antagonists Cyprodime, Naltrindole, or Nor-binaltorphimine, which specifically block mü, delta and kappa opioid receptors, respectively. In the 7th experimental day, rats were euthanized and their maxillae collected for evaluation of alveolar bone and fiber attachment loss, morphometric counting of osteoclasts and osteoblasts, as well as the levels of cytokines IL-1β, IFN-γ, and IL-6 by ELISA. Selective antagonism of kappa opioid receptors, but not mü and delta, exacerbated alveolar bone resorption induced by ligature in rats. The increased bone loss associated with higher number of osteoclasts surrounding alveolar bone, although osteoblasts' counting remained unchanged. The concentrations of IL-1β and IL-6 in periodontal tissues were also significantly higher in the rats treated with the kappa antagonist. Inhibiting kappa opioid receptors exacerbates alveolar bone resorption. [ABSTRACT FROM AUTHOR]

Secondary bacterial infections often complicate viral respiratory infections. We hypothesize that perturbation of the gut microbiota during influenza A virus (IAV) infection might favor respiratory bacterial superinfection. Sublethal infection with influenza transiently alters the composition and fermentative activity of the gut microbiota in mice. These changes are attributed in part to reduced food consumption. Fecal transfer experiments demonstrate that the IAV-conditioned microbiota compromises lung defenses against pneumococcal infection. In mechanistic terms, reduced production of the predominant short-chain fatty acid (SCFA) acetate affects the bactericidal activity of alveolar macrophages. Following treatment with acetate, mice colonized with the IAV-conditioned microbiota display reduced bacterial loads. In the context of influenza infection, acetate supplementation reduces, in a free fatty acid receptor 2 (FFAR2)-dependent manner, local and systemic bacterial loads. This translates into reduced lung pathology and improved survival rates of double-infected mice. Lastly, pharmacological activation of the SCFA receptor FFAR2 during influenza reduces bacterial superinfection. • Influenza alters the production of SCFAs by the gut microbiota • The dysbiotic microbiota transfers susceptibility to respiratory bacterial infection • Supplementation with acetate restores the killing activity of alveolar macrophages • Activation of the SCFA receptor FFAR2 protects against bacterial superinfection Sencio et al. provide insights into the mechanisms that underlie bacterial superinfection post-influenza. The authors demonstrate that influenza infection remotely alters the production of short-chain fatty acids (SCFAs) by the gut microbiota. Supplementation with acetate or pharmacological activation of the SCFA receptor FFAR2 reduces susceptibility to secondary bacterial infection. [ABSTRACT FROM AUTHOR]

The renin-angiotensin system (RAS), aside its classical hormonal properties, has been implicated in the pathogenesis of inflammatory disorders. The angiotensin converting enzyme 2/angiotensin-(1-7)/Mas Receptor (ACE2/Ang-(1-7)/MasR) axis owns anti-inflammatory properties and was recently associated with bone remodeling in osteoporosis. Thus, the aim of this study was to characterize the presence and effects of the ACE2/Ang-(1-7)/MasR axis in osteoblasts and osteoclasts in vitro and in vivo. ACE2 and MasR were detected by qPCR and western blotting in primary osteoblast and osteoclast cell cultures. Cells were incubated with different concentrations of Ang-(1-7), diminazene aceturate (DIZE – an ACE2 activator), A-779 (MasR antagonist) and/or LPS in order to evaluate osteoblast alkaline phosphatase and mineralized matrix, osteoclast differentiation and cytokine expression, and mRNA levels of osteoblasts and osteoclasts markers. An experimental model of alveolar bone resorption triggered by dysbiosis in rats was used to evaluate bone remodeling in vivo. Rats were treated with Ang-(1-7), DIZE and/or A-779 and periodontal samples were collected for immunohistochemistry, morphometric analysis, osteoblast and osteoclast count and cytokine evaluation. Human gingival samples from healthy and periodontitis patients were also evaluated for detection of ACE2 and MasR expression. Osteoblasts and osteoclasts expressed ACE2 and MasR in vitro and in vivo. LPS stimulation or alveolar bone loss induction reduced ACE2 expression. Treatment of bone cells with Ang-(1-7) or DIZE stimulated osteoblast ALP, matrix synthesis, upregulated osterix, osteocalcin and collagen type 1 transcription, reduced IL-6 expression, and decreased osteoclast differentiation, RANK and IL-1β mRNA transcripts, and IL-6 and IL-1β levels, in a MasR-dependent manner. In vivo , Ang-(1-7) and DIZE decreased alveolar bone loss through improvement of osteoblast/osteoclast ratio. A-779 reversed such phenotype. ACE2/Ang-(1-7)/MasR axis activation reduced IL-6 expression, but not IL-1β. ACE2 and MasR were also detected in human gingival samples, with higher expression in the healthy than in the inflamed tissues. These findings show that the ACE2/Ang-(1-7)/MasR is an active player in alveolar bone remodeling. Unlabelled Image • Osteoblasts and osteoclasts express ACE2 and MasR. • ACE2/Ang-(1-7)/MasR axis activation stimulates osteoblasts and inhibits osteoclasts. • ACE2/Ang-(1-7)/MasR axis activation reduces bone resorption triggered by dysbiosis. • ACE2 and MasR expression is downregulated in human samples of periodontitis patients. [ABSTRACT FROM AUTHOR]

Introduction: Cytokines and chemokines regulate bone remodeling during orthodontic tooth movement. CC chemokine ligand 2 (CCL2) is involved in osteoclast recruitment and activity, and its expression is increased in periodontal tissues under mechanical loading. In this study, we investigated whether the CC chemokine receptor 2 (CCR2)-CCL2 axis influences orthodontic tooth movement. Methods: A coil spring was placed in CCR2-deficient (CCR2−/−), wild-type, vehicle-treated, and P8A-treated (CCL2 analog) mice. In a histopathologic analysis, the amounts of orthodontic tooth movement and numbers of osteoclasts were determined. The expression of mediators involved in bone remodeling was evaluated by real-time polymerase chain reaction. Results: Orthodontic tooth movement and the number of TRAP-positive cells were significantly decreased in CCR2−/− and P8A-treated mice in relation to wild-type and vehicle-treated mice, respectively. The expressions of RANKL, RANK, and osteoblasts markers (COL-1 and OCN) were lower in CCR2−/− than in wild-type mice. No significant difference was found in osteoprotegerin levels between the groups. Conclusions: These data suggested a reduction of osteoclast and osteoblast activities in the absence of CCR2. The CCR2-CCL2 axis is positively associated with osteoclast recruitment, bone resorption, and orthodontic tooth movement. Therefore, blockage of the CCR2-CCL2 axis might be used in the future for modulating the extent of orthodontic tooth movement. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Orthodontic tooth movement (OTM) is achieved by alveolar bone remodelling induced by mechanical loading. Whilst interleukin-1 (IL-1) is directly involved in OTM, the role of interleukin-1 receptor antagonist (IL-1Ra), a naturally occurring IL-1 antagonist, is not completely defined. Therefore, the aim of this study was to investigate the effects of IL-1Ra on OTM. Methods: An orthodontic appliance was placed in C57BL6 mice treated with vehicle or IL-1Ra (10mg/kg/day). OTM and TRAP-positive osteoclasts were evaluated after 12 days of mechanical loading and the levels of cytokines on periodontal tissues were analysed by ELISA after 12 and 72h. Results: Mice treated with IL-1Ra showed diminished OTM and decreased numbers of TRAP-positive osteoclasts. In line with this, lower levels of IL-1β and TNF-α, and higher levels of IL-10, were observed on periodontal tissues of IL-1Ra-treated mice in relation to the vehicle-treated group. Conclusion: The present study suggests that IL-1Ra downregulates OTM, probably by its anti-inflammatory actions. [Copyright &y& Elsevier]

Abstract: Aim: The aim of this study was to evaluate early detection of temporomandibular joint (TMJ) inflammatory changes based on 1-thio-β-d-glucose radiolabeled with technetium-99m. Method: The method applied a TMJ inflammation model in rats followed by radiopharmaceutical synthesis, intravenous administration of 99mTc-1-TG and kinetic scintigraphy imaging. Results: Results show a significant difference of 99mTc-1-TG uptake between inflamed TMJ and the control joint. The biodistribution of 99mTc-1-TG by images showed the kidneys’ excretion. Conclusion: As conclusion, 99mTc-1-TG is a helpful tool in TMJ inflammatory process detection. [Copyright &y& Elsevier]

Leishmaniases, a group of diseases caused by the species of the protozoan parasite Leishmania , remains a significant public health concern worldwide. Host immune responses play a crucial role in the outcome of Leishmania infections, and several mediators that regulate inflammatory responses are potential targets for therapeutic approaches. Annexin A1 (AnxA1), an endogenous protein endowed with anti-inflammatory and pro-resolving properties, has emerged as a potential player. We have shown that during L. braziliensis infection, deficiency of AnxA1 exacerbates inflammatory responses but does not affect parasite burden. Here, we have investigated the role of AnxA1 in L. amazonensis infection, given the non-healing and progressive lesions characteristic of this infectious model. Infection of AnxA1 KO BALB/c mice resulted in increased lesion size and tissue damage associated with higher parasite burdens and enhanced inflammatory response. Notably, therapeutic application of the AnxA1 peptidomimetic Ac2–26 improves control of parasite replication and increases IL-10 production in vivo and in vitro , in both WT and AnxA1 KO mice. Conversely, administration of WRW4, an inhibitor of FPR2/3, resulted in larger lesions and decreased production of IL-10, suggesting that the effects of AnxA1 during L. amazonensis infection are associated with the engagement of these receptors. Our study illuminates the role of AnxA1 in L. amazonensis infection, demonstrating its impact on the susceptibility phenotype of BALB/c mice. Furthermore, our results indicate that targeting the AnxA1 pathway by using the Ac2–26 peptide could represent a promising alternative for new treatments for leishmaniasis. [Display omitted] • The role of the mediator AnxA1 in Leishmania infection is not yet understood. • Lack of endogenous AnxA1 increases susceptibility of BALB/c mice to Leishmania amazonensis infection. • Treatment with the peptide Ac2- 26 reduces lesion progression, induces IL-10 production and improves parasite clearance. • Inhibition of the AnxA1 receptor FPR2 results in larger lesions in infected BALB/c mice. • Ac2-26 is a potential target for immunotherapy treatment in Leishmania infection. [ABSTRACT FROM AUTHOR]

COVID-19 affects primarily the lung. However, several other systemic alterations, including muscle weakness, fatigue and myalgia have been reported and may contribute to the disease outcome. We hypothesize that changes in the neuromuscular system may contribute to the latter symptoms observed in COVID-19 patients. Here, we showed that C57BL/6J mice inoculated intranasally with the murine betacoronavirus hepatitis coronavirus 3 (MHV-3), a model for studying COVID-19 in BSL-2 conditions that emulates severe COVID-19, developed robust motor alterations in muscle strength and locomotor activity. The latter changes were accompanied by degeneration and loss of motoneurons that were associated with the presence of virus-like particles inside the motoneuron. At the neuromuscular junction level, there were signs of atrophy and fragmentation in synaptic elements of MHV-3-infected mice. Furthermore, there was muscle atrophy and fiber type switch with alteration in myokines levels in muscles of MHV-3-infected mice. Collectively, our results show that acute infection with a betacoronavirus leads to robust motor impairment accompanied by neuromuscular system alteration. • Betacoronavirus infection causes motor impairment. • Motoneuron loss is caused by betacoronavirus infection. • Betacoronavirus infection causes neuromuscular junction degeneration. • Skeletal muscle atrophy is developed after betacoronavirus infection. [ABSTRACT FROM AUTHOR]