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Background: Annexin A1 (ANXA1) and the NOD‐like receptor family pyrin domain‐containing protein 3 (NLRP3) inflammasome play important roles in bone remodeling. However, expression profiles of these factors in bone cells under diabetes mellitus (DM) and estrogen‐deficient conditions are poorly understood. This study investigated the immunoexpression of ANXA1 and its formyl peptide receptor 2 (FPR2), as well as NLRP3 inflammasome mediators, during remodeling of the alveolar process in diabetic and estrogen‐deficient rats. Methods: Twenty adult female Wistar rats were divided into four groups (n = 5): Sham‐operated (SHAM) and ovariectomized (OVX) rats received a vehicle solution, and SHAM and OVX rats were intraperitoneally administered 60 mg/kg/body weight (BW) of streptozotocin (STZ) to induce DM (SHAM‐Di and OVX‐Di groups). After 7 weeks, the rats were euthanized and their maxillae were fixed in phosphate‐buffered 4% formaldehyde and embedded in paraffin. Sections were stained with hematoxylin/eosin (H&E) and picrosirius red or subjected to immunohistochemical detection of ANXA1, FPR2, NLRP3, interleukin‐1β (IL‐1β), and cyclooxygenase‐2 (COX2). Results: Estrogen deficiency and DM were associated with deleterious effects in bone tissue, as evidenced by a lower number of osteocytes and higher number of empty lacunae in the SHAM‐Di and OVX‐Di groups compared to the nondiabetic groups. Both diabetic groups showed a smaller vascular area and weaker collagen fiber birefringence intensity in alveolar bone tissue. A significantly higher number of ANXA1/FPR2‐positive osteoblasts, osteocytes, and osteoclasts was accompanied by a significantly higher number of these cells immunolabeled for COX2, NLRP3, and IL‐1β in the diabetic and OVX groups, especially in both estrogen‐deficient and diabetic rats. Conclusion: These results indicate a possible role for the ANXA1/FPR2 pathway as a fine‐tuning/anti‐inflammatory regulator to counterbalance exacerbated COX2/NLRP3/IL‐1β activation in bone cells during bone remodeling under estrogen deficiency and DM. [ABSTRACT FROM AUTHOR]

Background: Paroxetine, a selective serotonin reuptake inhibitor (SSRI) antidepressant, has caused male sexual dysfunction; however, the paroxetine mechanisms of action in testes are still unclear. Objectives: Paroxetine serotonergic effects in testes were evaluated, focusing on steroidogenesis and the correlation between macrophages population and possible TNF‐α‐derived oxidative stress. We also verified whether the changes are reversible following treatment interruption. Materials and methods: Adult rats received paroxetine (PG35 and PG65) or tap water (CG) for 35 days. PG65 was maintained without treatment for 30 more days. Intratesticular testosterone (IT), nitrite, and malondialdehyde concentrations were measured. To confirm serotonergic and estrogenic effects, Htr1b and Esr1 expressions were analyzed. The daily sperm production (DSP), frequency of abnormal seminiferous tubules (ST), SC number, ST area, and Leydig cells nuclear area (LCnu) were evaluated. TUNEL+ germ cells, M1 (CD68+), and M2 (Perls+) macrophages were quantified. 17β‐HSD7, CYP19A1, NDRG2, oxytocin, TNF‐α, and iNOS were evaluated by immunoreactions. Oxytocin and NDRG2 protein levels as well as Tnfa mRNA expression were also analyzed. Results: The Htr1b downregulation in testes confirmed the paroxetine serotonergic effect. The testicular sections showed abnormal ST frequency, ST atrophy and reduction of DSP, LCnu, SC number and Perls+ macrophages. TUNEL+ germ cells and LC were associated with strong NDRG2 immunoexpression. Paroxetine reduced IT levels and 17β‐HSD7 immunoexpression in parallel to increased CYP19A1, oxytocin, TNF‐α and iNOS. Esr1 and Tnfa overexpression and increased number of CD68+ macrophages were also observed together with high nitrite and malondialdehyde levels. Most parameters were not recovered in PG65. Conclusions: Paroxetine serotonergic effect impairs LC steroidogenesis, via aromatization, increasing estrogen/testosterone ratio, which in turn upregulate NDRG2, promoting apoptosis, and impairing sperm production. Serotonin–estrogen pathways may be responsible for M2/M1 polarization, Tnfa upregulation, and induction of oxidative stress. The unrecovered testicular changes after treatment discontinuation are due to persistent paroxetine serotonin/estrogen effects. [ABSTRACT FROM AUTHOR]

Aim: To evaluate whether the bioceramic materials Bio‐C Pulpo (Bio‐C, Angelus) and mineral trioxide aggregate (MTA) Repair HP (MTA‐HP, Angelus) induce fibroblast proliferation and release of interleukin‐10 (IL‐10), an anti‐inflammatory cytokine, stimulating connective tissue remodelling. The tissue response of Bio‐C and MTA‐HP was compared with the White MTA (WMTA; Angelus) since studies have demonstrated that WMTA induces tissue repair. Methodology: Bio‐C, MTA‐HP and WMTA were inserted into polyethylene tubes and implanted in the subcutaneous tissue of Holtzman rats for 7, 15, 30 and 60 days. As a control group (CG), empty tubes were implanted subcutaneously. The number of fibroblasts (FB), Ki‐67‐, fibroblast growth factor‐1‐ (FGF‐1) and IL‐10‐immunolabelled cells and collagen content in the capsules was obtained. The data were subjected to two‐way anova followed by Tukey's test (p ≤.05). Results: At 7 days, significant differences in the number of FB were not detected amongst Bio‐C, MTA‐HP and WMTA groups (p ˃.05). The capsules of all groups exhibited a significant increase in the number of FB and content of collagen over time. From 7 to 60 days, a significant reduction in the number of FGF‐1‐ and Ki‐67‐immunolabelled cells was seen in the capsules of all specimens. In all periods, no significant difference in the number of FGF‐1‐immunolabelled cells was detected between Bio‐C and CG specimens. At 60 days, significant differences in the immunoexpression of FGF‐1 were not observed amongst the groups. At 7 and 15 days, the highest immunoexpression for Ki‐67 was present in Bio‐C specimens whilst, after 30 and 60 days, no significant difference was observed amongst the bioceramic materials. At 7 days, few IL‐10 immunolabelled cells were present in the capsules of all specimens whereas, at 60 days, a significant increase in the IL‐10‐immunostaining was present in all groups. At 60 days, the Bio‐C, MTA‐HP and WMTA groups showed a greater number of IL‐10‐immunolabelled cells than in the CG specimens (p <.0001). Conclusions: Bio‐C, MTA‐HP and WMTA stimulate fibroblast proliferation, leading to the formation of collagen‐rich capsules. FGF‐1 and IL‐10 may mediate the remodelling of capsules around Bio‐C, MTA‐HP and WMTA bioceramic materials. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the tissue reaction of a tricalcium silicate‐based repair material associated with 30% calcium tungstate (TCS + CaWO4) in comparison to Bio‐C Repair (Bio‐C; Angelus) and to MTA Repair HP (MTA HP; Angelus). Methodology: Polyethylene tubes filled with one of the materials or left empty (control group, CG) were implanted into the subcutaneous tissues of rats for 7, 15, 30 and 60 days (n = 32/group). The capsule thickness, number of inflammatory cells, collagen content, interleukin‐6 (IL‐6), osteocalcin (OCN), von Kossa reaction and analysis under polarized light were evaluated. The data were subjected to generalized linear models for repeated measures, except the OCN. OCN data were submitted to Kruskal–Wallis and Dunn's post hoc test and Friedman followed by Nemenyi's test at significance level of 5%. Results: At all time points, significant differences in the number of inflammatory cells were not observed between TCS + CaWO4 and Bio‐C, whereas, at 15, 30 and 60 days, no significant difference was detected between TCS + CaWO4 and MTA HP. At all periods, significant differences were not detected in the number of fibroblasts in TCS + CaWO4 versus MTA HP, and, at 60 days, no significant difference was demonstrated between these groups and CG. Significant differences in the immunoexpression of IL‐6 were not detected amongst bioceramic materials at all periods. From 7 to 60 days, significant reduction in the number of inflammatory cells, number of IL‐6‐immunopositive cells and in the capsule thickness was accompanied by significant increase in the collagen in all groups. OCN‐immunolabelled cells, von Kossa‐positive structures and amorphous calcite deposits were observed around all materials, whereas, in the CG, these structures were not seen. Conclusions: These findings indicate that the experimental material (TCS + CaWO4) is biocompatible and has a bioactive potential, similar to the MTA HP and Bio‐C Repair, and suggest its use as a root repair material. [ABSTRACT FROM AUTHOR]