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BACKGROUND: Collagen is a component of Pyogenic Granuloma (PG) and Peripheral Ossifying Fibroma (POF) and performs different functions in these lesions. The objective of this study is to evaluate the role of collagen and immunostaining for Transforming Growth Factor beta (TGF-ß) in the clinical and microscopic findings of PG and POF. MATERIAL AND METHODS: PG (n=20) and POF (n=20) were selected for clinical evaluation (sex, age, localization, size and evolution time) and microscopic analysis (picrosirius red staining for collagen analysis and immunohistochemistry for TGF-ß) performed in the superficial and deep areas of the two lesions. ANOVA/Bonferroni and t-test, Pearson correlation and χ2 were used to compare the sites and parameters analyzed (p<0.05, GraphPad Prism 5.0). RESULTS: The depth of PG presented the highest amount of collagen (p<0.001), and its surface showed the lowest amount of type 1 collagen (yellow-red strong birefringence). Type 1 collagen gradually increased in depth of PG, surface and depth of POF (p<0.001). The number of TGF-ß+ cells was lower on the surface of PG compared with the depth of PG and the two areas of POF (p<0.001). Sex and localization did not affect these parameters, but the profile of collagen and immunostaining for TGF-ß suffered from modifications by the time of evolution and the size of the lesion. CONCLUSIONS: Although PG and POF are reactive gingival lesions, the expression of TGF-ß and its role in collagen showed different biological behaviors in these lesions, suggesting different biological origins for its components.

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BACKGROUND: This study aimed to analyze whether immunohistochemistry (IHC) is more sensitive than hematoxylin-eosin (H&E) staining for identifying perineural invasion (PNI) or lymphovascular invasion (LVI) in oral squamous cell carcinoma (OSCC). MATERIAL AND METHODS: In this systematic review and meta-analysis (Prospective Register of Systematic Reviews - CRD 42021256515), data were obtained from six databases (PubMed, Scopus, LILACS, Web of Science, EBSCO, LIVIVO, Embase) and the grey literature. Cross-sectional observational studies of the diagnostic sensitivity of IHC for PNI and LVI were included. Studies were selected in two phases: first collection and reference retrieval. The Quality Assessment of Diagnostic Accuracy Studies-2 tool assessed study quality, while the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach assessed evidence quality. The meta-analysis (random effects model) was performed using MedCalc 18.2.1 software (MedCalc®) (p<0.05). RESULTS: Four studies (560 patients with 295 biopsies) were analyzed. The combined sensitivity was 76% (95% confidence interval [CI], 44.30-97.19%) and specificity was 42% (95% CI, 23.40-62.02%). The positive predictive value (PPV) and negative predictive value (NPV) were 61% (95% CI, 49.78-71.53%) and 70% (95% CI, 37.63-94.43%). The overall accuracy was 58% (95% CI, 45.17-70.65%). The risk of bias was low, and GRADE analysis showed a very low certainty of evidence. CONCLUSIONS: Our data suggest that IHC staining to highlight PNI/LVI may be useful in cases in which H&E analysis results in a negative decrease in the prevalence of false-negative cases and underestimated treatment.

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Nonalcoholic fatty liver disease (NAFLD), characterized by hepatosteatosis and steatohepatitis, is intrinsically related to obesity. Our previous study reported on the anti-obese activity of α,ß-amyrin (AMY), a pentacyclic triterpene isolated from Protium heptaphyllum. This study investigated its ability to prevent fatty liver and the underlying mechanism using the mouse model of NAFLD. NAFLD was induced in male Swiss mice fed a high fat diet (HFD) for 15 weeks. The controls were fed a normal chow diet (ND). The mice were simultaneously treated with AMY at 10 and 20 mg/kg or fenofibrate at 50 mg/kg. Lipid levels along with metabolic and inflammatory parameters were assessed in liver and serum. The liver sections were histologically examined using H&E staining. RT-qPCR and western blotting assays were performed to analyze signaling mechanisms. Mice fed HFD developed severe hepatic steatosis with elevated triglycerides and lipid droplets compared with ND controls. This was associated with a decrease in AMP-activated protein kinase (AMPK) activity, an increase of mechanistic target of rapamycin complex 1 (mTORC1) signaling, and enhanced sterol regulatory element binding protein 1 (SREBP1) expression, which have roles in lipogenesis, inhibition of lipolysis, and inflammatory response. AMY treatment reversed these signaling activities and decreased the severity of hepatic steatosis and inflammatory response, evidenced by serum and liver parameters as well as histological findings. AMY-induced reduction in hepatic steatosis seemed to involve AMPK-mTORC1-SREBP1 signaling pathways, which supported its beneficial role in the prevention and treatment of NAFLD.

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It was previously demonstrated that the methanol fraction of Sideroxylon obtusifolium (MFSOL) promoted anti-inflammatory and healing activity in excisional wounds. Thus, the present work investigated the healing effects of MFSOL on human keratinocyte cells (HaCaT) and experimental burn model injuries. HaCaT cells were used to study MFSOL's effect on cell migration and proliferation rates. Female Swiss mice were subjected to a second-degree superficial burn protocol and divided into four treatment groups: Vehicle, 1.0% silver sulfadiazine, and 0.5 or 1.0% MFSOL Cream (CrMFSOL). Samples were collected to quantify the inflammatory mediators, and histological analyses were performed after 3, 7, and 14 days. The results showed that MFSOL (50 µg/mL) stimulated HaCaT cells by increasing proliferation and migration rates. Moreover, 0.5% CrMFSOL attenuated myeloperoxidase (MPO) activity and also stimulated the release of interleukin (IL)-1ß and IL-10 after 3 days of treatment. CrMFSOL (0.5%) also enhanced wound contraction, promoted improvement of tissue remodeling, and increased collagen production after 7 days and VEGF release after 14 days. Therefore, MFSOL stimulated human keratinocyte (HaCaT) cells and improved wound healing via modulation of inflammatory mediators of burn injuries.

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It was previously demonstrated that the methanol fraction of Sideroxylon obtusifolium (MFSOL) promoted anti-inflammatory and healing activity in excisional wounds. Thus, the present work investigated the healing effects of MFSOL on human keratinocyte cells (HaCaT) and experimental burn model injuries. HaCaT cells were used to study MFSOL's effect on cell migration and proliferation rates. Female Swiss mice were subjected to a second-degree superficial burn protocol and divided into four treatment groups: Vehicle, 1.0% silver sulfadiazine, and 0.5 or 1.0% MFSOL Cream (CrMFSOL). Samples were collected to quantify the inflammatory mediators, and histological analyses were performed after 3, 7, and 14 days. The results showed that MFSOL (50 μg/mL) stimulated HaCaT cells by increasing proliferation and migration rates. Moreover, 0.5% CrMFSOL attenuated myeloperoxidase (MPO) activity and also stimulated the release of interleukin (IL)-1β and IL-10 after 3 days of treatment. CrMFSOL (0.5%) also enhanced wound contraction, promoted improvement of tissue remodeling, and increased collagen production after 7 days and VEGF release after 14 days. Therefore, MFSOL stimulated human keratinocyte (HaCaT) cells and improved wound healing via modulation of inflammatory mediators of burn injuries.

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Nonalcoholic fatty liver disease (NAFLD), characterized by hepatosteatosis and steatohepatitis, is intrinsically related to obesity. Our previous study reported on the anti-obese activity of α,β-amyrin (AMY), a pentacyclic triterpene isolated from Protium heptaphyllum. This study investigated its ability to prevent fatty liver and the underlying mechanism using the mouse model of NAFLD. NAFLD was induced in male Swiss mice fed a high fat diet (HFD) for 15 weeks. The controls were fed a normal chow diet (ND). The mice were simultaneously treated with AMY at 10 and 20 mg/kg or fenofibrate at 50 mg/kg. Lipid levels along with metabolic and inflammatory parameters were assessed in liver and serum. The liver sections were histologically examined using H&E staining. RT-qPCR and western blotting assays were performed to analyze signaling mechanisms. Mice fed HFD developed severe hepatic steatosis with elevated triglycerides and lipid droplets compared with ND controls. This was associated with a decrease in AMP-activated protein kinase (AMPK) activity, an increase of mechanistic target of rapamycin complex 1 (mTORC1) signaling, and enhanced sterol regulatory element binding protein 1 (SREBP1) expression, which have roles in lipogenesis, inhibition of lipolysis, and inflammatory response. AMY treatment reversed these signaling activities and decreased the severity of hepatic steatosis and inflammatory response, evidenced by serum and liver parameters as well as histological findings. AMY-induced reduction in hepatic steatosis seemed to involve AMPK-mTORC1-SREBP1 signaling pathways, which supported its beneficial role in the prevention and treatment of NAFLD.

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Objetivou-se, com este estudo, avaliar o processo de cicatrização da musculatura reto-abdominal em coelhos submetidos à laparorrafia, utilizando-se o fio de sutura à base de quitosana, comparando-o aos fios de categute cromado e poliglactina 910. Foram utilizados 24 coelhos adultos, divididos aleatoriamente em quatro grupos: quitosana e categute 15 dias (QC-15dias), quitosana e categute 30 dias (QC-30 dias), quitosana e poliglactina 910 15 dias (QP-15 dias) e quitosana e poliglactina 910 30 dias (QP-30 dias). Cada grupo foi composto por seis coelhos, nos quais foram realizadas duas incisões, uma do lado direito e outra do lado esquerdo e, posteriormente, a laparorrafia, com o fio de quitosana de um lado e o categute cromado ou poliglactina 910 do outro. Realizou-se análise clínico-cirúrgica, histológica e avaliação de achados de necropsia, além de testes de citotoxicidade e de mecânica no fio de quitosana. Ele apresentou baixa resistência mecânica e citotóxica. O fio de quitosana não proporcionou uma cicatrização satisfatória em coelhos, pois desencadeou uma resposta inflamatória acentuada.(AU)

The objective of this study was to evaluate the healing process of the recto-abdominal muscles in rabbits submitted to laparorrhaphy using chitosan-based suture yarn, comparing it to chrome catgut and polyglactin 910 yarns. Twenty-four adult rabbits were divided in to four random groups: chitosan and polyglactin 910 15 days (QP-15 days) and chitosan and polyglactin 910 30 days (QC-30 days), chitosan and polyglactin 910 15 days (QP-15 days) QP-30 days). Each group consisted of six rabbits, in which two incisions were made, one on the right side and one on the left side, and later the laparorraphy with the chitosan yarn on one side and chromed catgut or polyglactin 910 on the other. Clinical-surgical, histological and necropsy findings were evaluated, as well as cytotoxicity and mechanical tests on the chitosan wire. It presented low mechanical and cytotoxic resistance. Chitosan thread did not provide satisfactory healing in rabbits, as it triggered a marked inflammatory response.(AU)

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This study aims to determine the antitumor potential of cashew gum in vitro and in vivo. The cashew gum (CG) structure is similar to already showed in literature. The cytotoxicity effect of CG was performed by MTT assay, and B16-F10 melanoma model was used to evaluate antitumor effect. The tumor inhibition was calculated based on tumor weight. Hematological, histopathological, FTIR, oxidative stress and Western Blot analysis were performed to elucidate the mechanism of inhibition and toxic effects. As results, CG did not demonstrate cytotoxicity in vitro, however showed a significant tumor inhibition in vivo, with about 36.9 to 43% of reduction in tumor mass, with no toxicity to organs. Animals treated with CG did not show toxicity in normal tissues, FTIR spectrum and oxidative stress analysis of the tumor tissue indicated that CG cause tumor inhibition with the presence of apoptosis morphotype cells, without alterations in the levels of antioxidants components. In addition, it was observed that CG reduced the expression of γH2AX without changing the expression of caspase-3. With this, we can suggest that this polymer can assist in the anticancer activity and/or decrease the side effects of standard drugs used in treatment of cancer.

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This manuscript describes the experimental observation of vasculogenesis in chick embryos by means of network analysis. The formation of the vascular network was observed in the area opaca of embryos from 40 to 55 h of development. In the area opaca endothelial cell clusters self-organize as a primitive and approximately regular network of capillaries. The process was observed by bright-field microscopy in control embryos and in embryos treated with Bevacizumab (Avastin®), an antibody that inhibits the signalling of the vascular endothelial growth factor (VEGF). The sequence of images of the vascular growth were thresholded, and used to quantify the forming network in control and Avastin-treated embryos. This characterization is made by measuring vessels density, number of cell clusters and the largest cluster density. From the original images, the topology of the vascular network was extracted and characterized by means of the usual network metrics such as: the degree distribution, average clustering coefficient, average short path length and assortativity, among others. This analysis allows to monitor how the largest connected cluster of the vascular network evolves in time and provides with quantitative evidence of the disruptive effects that Avastin has on the tree structure of vascular networks.

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BACKGROUND: The aim of the present study was to analyze the epidemiological data of digital panoramic radiographs revealing suggestive images of carotid artery calcifications (CAC) from a Northeast Brazilian population. MATERIAL AND METHODS: A cross-sectional retrospective study was conducted with 2,500 digital panoramic radiographs obtained from a single imaging reference center in Northeast Brazil. Images from individuals of both sexes and older than 18 years were included and those that did not cover the region of cervical vertebrae or presented low radiographic quality were excluded. Data were analyzed regarding prevalence, location (bilateral, right or left), sex, and age using the Chi-square test at the significance level of 5%. RESULTS: An amount of 96 (4%) patients presented suggestive images of CAC. The female sex (p=0.003) and individuals aged up to 70 years (p=0.002) were statically significant. 40.4% were found bilaterally, 37.6% on the right side (p<0.001) and 22% on the left side. CONCLUSIONS: In conclusion, this study showed a low prevalence of suggestive images of CAC in digital panoramic radiographs from a Northeast Brazilian population. It was observed a higher prevalence of CAC associated with female sex, older patients, and right side location.

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