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Introduction: The association between triamcinolone hexacetonide (TH) and gold nano-particles (GNPs) represents a promising treatment due to the potential anti-inflammatory and anti-oxidant effects of these compounds. In this study, we evaluated the effects of intra-articular treat-ment of TH associated with GNPs in a mechanical model of osteoarthritis (OA). Methods: Fifty Wistar rats were divided into five groups: Sham; OA; OA+TH; OA+GNPs; OA+TH-GNPs. Both applications were performed 30 and 60 days after the model was induced. Af-ter 30 days of the last application, the animals were euthanized. Results: Only the combined treatment with TH and GNPs promoted a reduction in pro-inflammatory cytokines and an increase in anti-inflammatory cytokines. The OA+TH-GNPs group obtained a significant reduction in the production of oxidants and oxidative damage markers while an increase in antioxidants. Histologically, all treated groups showed results of a significant increase in cartilage thickness and chondrocyte count, the OA+TH-GNPs group had similar behavior to the group without osteoarthritis, with significantly smaller amounts of chondrocytes than the OA group. Conclusion: The intra-articular use of TH associated with GNPs may be able to prevent the pro-gression of the pathology and minimize joint degradation.

Background: Oxidative stress is a key factor in the worsening of diabetes, requiring an increase in the activity of the antioxidant system, culminating in a balance in the body. The aim of the present study was to evaluate the redox state in the skeletal and cardiac muscles in rats induced to diabetes model and submitted to swimming exercise training for 4 weeks. Methods: Wistar rats were separated into the following four groups: untrained control (C); trained control (T); untrained alloxan-induced diabetes (D); trained alloxan-induced diabetes (TD). The animals were submitted to swimming exercise training for 4 weeks. The redox state of skeletal and cardiac muscles was analyzed by TBARS, -SH groups and, H2O2 production as well as by the SOD and Catalase activity. Besides, a histomorphometry analysis was performed in the cardiac muscle in which the total number of cardiomyocytes and the total area of collagen fibers were measured.Results: On the Soleus muscles, the TD group showed increased of H2O2 and Catalase compared to T group; and SOD compared to D group. About the red gastrocnemius, TD group presented higher SOD and lower Catalase relation to D group. Regarding to cardiac muscle, TD group presented lower TBARS than D group, while it was higher in -SH groups and Catalase compared to D group. Moreover, the swimming exercise led to a decrease in hyperglycemia, benefits in pathogenesis and physio-pathogenesis, evidenced by a reduced number of cardiomyocytes and area of collagen fibers. Conclusions: The swimming protocol exercise in diabetic rats was able to control the hyperglycemia, control of oxidative damage and minimize the fibrosis on cardiac muscle in diabetic rats.

Background The repair of burns in diabetic patients is a clinical problem. It is relevant to study alternative therapies that can improve the healing process. Our aim was to investigate the effects of Solidago chilensis associated or not with laser on burns in diabetic rats. Methods The animals were divided in four groups (n = 30): C- without treatment; S– S. chilensis extract; L-laser irradiated; LS- laser and S. chilensis. In 7, 14 and 21 days samples were collected after the injury to structural, morphometric and molecular analysis. Results Our results demonstrate the association of S. chilensis and laser reduced the inflammatory infiltrate and favored the angiogenesis. In the groups treated only with laser or with the plant, extract showed higher levels of VEGF. The LLLT promoted higher collagen I and reduction of collagen III. It was also observed higher MMP-2 activation and a decreasing of the active isoform of MMP-9 in the S, L and LS groups. Conclusions The treatments improved the repair of burns in diabetic rats, since it reduced the inflammatory infiltrate and favored the collagen organization presenting similar effects in the burn repair of the diabetics.

Diabetes mellitus, which is characterized by hyperglycemia, leads to poor wound healing. Azadirachta indica has antidiabetic properties and further promotes the healing of epidermal wounds. Here, we investigated the effects of topical application of A. indica extract on excisional lesions in hyperglycemic rats. The animals were divided into four groups (n=15): non-hyperglycemic and treated with carbopol gel (NH), non-hyperglycemic and treated with A. indica + carbopol gel (NHT), hyperglycemic and treated with carbopol gel (H), and hyperglycemic and treated with A. indica + carbopol gel (HT). Lesions were made on the animals’ back, with a punch of 1.5-cm diameter. Samples of the skin/lesion were collected on the 2nd, 7th, and 14th days post-injury for histological examination (inflammatory infiltrate, blood vessels, and fibroblasts), biochemical analysis (MPO [myeloperoxidase], neutrophilic infiltrate and NAG [N-acetylglycosaminidase], and macrophagic infiltrate), oxidative stress (oxidants such as NO [nitric oxide] and DCF [2′,7′-dichlorodihydrofluorescein diacetate], oxidative damage by carbonyl sulfhydryl radicals, and antioxidants such as SOD [superoxide dismutase] and GSH [glutathione]), and analysis of reepithelialization by assessing the wound healing rate. The topical application of A. indica extract in the excisional wounds of hyperglycemic rats accelerated wound healing through anti-inflammatory, antioxidant, angiogenic, and fibrillogenic effects. Thus, these results show that A. indica extract has the potential to be used as a therapeutic agent for treating excisional wounds in hyperglycemic.

This study aimed to evaluate the effects of intra-articular treatment with hyaluronic acid (HA) associated with GNPs in a mechanical model of osteoarthritis induced by median meniscectomy (MM). Fifty Wistar rats (2 months weighing between 250 and 300 g) were used, divided into five groups of 10 animals each: Sham, osteoarthritis (OA), OA + HA, OA + gold nanoparticles (GNPs), and OA + HA + GNPs. Intra-articular treatment was started 30 days after the model was induced, with a frequency of 2 weeks for 60 days. Fifteen days after the last application, the animals were euthanized with the removal of the joint tissue for biochemical and histological analysis. The model used was able to mimic osteoarthritis, characterized by the presence of high levels of proinflammatory cytokines, oxidative stress, and degeneration of joint surfaces (Grade III, according to SCORE OARSI). The isolated use of HA or GNPs provided beneficial results to the joint; however, only the group subjected to the association between HA and GNPs showed the attenuation of oxidative stress and reduced proinflammatory markers, with a simultaneous increase in levels of anti-inflammatory cytokines and growth factors. Upon histological analysis, only the OA + HA + GNPs group achieved the restoration of the thickness of the joint cartilage with reduced damage and return to the intact joint surface. The results found demonstrated that the association of GNPs with HA was able to reverse the deleterious effects caused by the model by inhibiting the progressive degeneration of joint surfaces, representing a promising treatment for osteoarthritis.

The literature has shown the beneficial effects of microcurrent (MC) therapy on tissue repair. We investigated if the application of MC at 10 μA/90 s could modulate the expression of remodeling genes transforming growth factor beta (Tgfb), connective tissue growth factor (Ctgf), insulin-like growth factor 1 (Igf1), tenascin C (Tnc), Fibronectin (Fn1), Scleraxis (Scx), Fibromodulin (Fmod) and tenomodulin in NIH/3T3 fibroblasts in a wound healing assay. The cell migration was analyzed between days 0 and 4 in both fibroblasts (F) and fibroblasts + MC (F+MC) groups. On the 4th day, cell viability and gene expression were also analyzed after daily MC application. Higher expression of Ctgf and lower expression of Tnc and Fmod, respectively, were observed in the F+MC group in relation to F group (p

The combination of electrical stimulation (ES) and bone tissue engineering (BTE) has been successful in treatments of bone regeneration. This study evaluated the effects of ES combined with PCL + β-TCP 5% scaffolds obtained by rotary jet spinning (RJS) in the regeneration of bone defects in the calvaria of Wistar rats. We used 120 animals with induced bone defects divided into 4 groups (n = 30): (C) without treatment; (S) with PCL+ β-TCP 5% scaffold; (ES) treated with ES (10 μA/5 min); (ES + S) with PCL + β-TCP 5% scaffold. The ES occurred twice a week during the entire experimental period. Cell viability (in vitro: Days 3 and 7) and histomorphometric, histochemical, and immunohistochemical (in vivo; Days 30, 60, and 90) analysis were performed. In vitro, ES + S increased cell viability after Day 7 of incubation. In vivo, it was observed modulation of inflammatory cells in ES therapy, which also promoted blood vessels proliferation, and increase of collagen. Moreover, ES therapy played a role in osteogenesis by decreasing ligand kappa B nuclear factor-TNFSF11 (RANKL), increasing alkaline phosphatase (ALP), and decreasing the tartarate-resistant acid phosphatase. The combination of ES with RJS scaffolds may be a promising strategy for bone defects regeneration, since the therapy controlled inflammation, favored blood vessels proliferation, and osteogenesis, which are important processes in bone remodeling.

Burns are a public health problem, with second-degree burns as one of the most common types. Although intense inflammation worsens burn healing, effective therapies are scarce. Thus, infections and hypertrophic scars may occur, which compromise patient quality of life and may delay healing. Argon atmospheric plasma (AP) has been shown to positively influence wound healing. In the context of identifying effective and alternative therapies for the treatment of second-degree burns, the present study evaluated AP in the treatment of second-degree burns in rats compared to that for sham treatment on the 2nd, 7th, 14th, and 21st days post-injury. Our results revealed proinflammatory effect for AP by recruiting predominantly neutrophils on the 7th day and macrophages on the 21st day compared to sham treatment, allowing a greater production of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-17, and also controlled the inflammation by IL-10 and transforming growth factor (TGF)-β1. AP also showed antioxidant activity important for controlling oxidative damage on the 2nd day. This favored the induction of angiogenesis from the 2nd day and induction fibroplasia and fibrillogenesis after the 14th day, which enhanced burn healing with the formation of a thinner burn eschar before the 21st day post-burn. Thus, AP effectively modulated the inflammatory phase of second-degree burn healing through the control of oxidative damage that favored the following phases. Therefore, AP is a relevant alternative in the treatment of second-degree burns.

Background Dermabrasion is related with mechanical and surgical traumas on the skin; usually topical antiseptics and/or saline have been used for healing. Natural products for wound healing can also be used for abrasions, such as latex from Hevea brasiliensis. Objective This study aimed to evaluate the in vitro viability and migratory/proliferative effects of latex serum from H. brasiliensis and to compare with a commercially available standard antiseptic solution and saline in experimental dermabrasion on rats. Methods For in vitro evaluation, MTT and scratch assays were used. In vivo testing was performed in 72 rats submitted to dermabrasion, treated with saline, antiseptic, or latex serum. This study evaluated re-epithelialization, neutrophilic infiltration, and the quantification of crust and epidermis. Results Latex showed viability at 1% and 0.1% concentrations and migratory/proliferative activity at 0.01% concentrations. The re-epithelialization was highest in latex group on 7th day. The latex group displayed lower thickness of crusts and greater extent of epidermal layers. The latex and antiseptic groups showed increases of myeloperoxidase levels on the 2nd day and showed important reductions from the 7th day. Study limitations Acute superficial wound model in rats and non-use of gel-cream (medium) without latex. Conclusion In conclusion, non-toxic latex stimulated migration/proliferation of keratinocytes in vitro and significantly accelerated wound healing in animal excoriation models compared to chlorhexidine or saline.

Evaluate the bone remodeling during orthodontic movement with corticotomy when submitted to low-intensity electrical stimulation application (microcurrent—MC) and low-level laser therapy (LLLT). One hundred and fifty Wistar rats were divided into the following 5 groups: (C) submitted to tooth movement; (Cort) tooth movement/corticotomy; (Cort-L) tooth movement/corticotomy/laser AsGaAl 808 nm (4.96J/50s); (Cort-Mc) tooth movement/corticotomy/microcurrent (10 μA/5 min); (Cort-L-Mc) tooth movement/corticotomy and laser/microcurrent alternated. Inflammation, angiogenesis, and osteogenesis were evaluated in the periodontal ligament (PDL) and alveolar bone on the 7th, 14th, and 21st days of orthodontic movement. The quantification of inflammatory infiltrate, angiogenesis and expression of TGF-β1, VEGF, and collagen type I were favorably modulated by the application of therapies such as low-level laser therapy (LLLT), MC, or both combined. However, electrical stimulation increased fibroblasts, osteoclasts and RANK numbers, birefringent collagen fiber organization, and BMP-7 and IL-6 expression. Low-level laser therapy (LLLT) and MC application both improved the process of bone remodeling during orthodontic treatment with corticotomy. Still, electrical current therapy promoted a more effective tooth displacement but presented expected root resorption similar to all experimental treatments. It is important to know the effects of minimally invasive therapies on cellular and molecular elements involved in the bone remodeling of orthodontic treatment associated with corticotomy surgery, in order to reduce the adverse effects in the use of this technique and to establish a safer clinical routine.

We propose a new family of distributions called the exponentiated Kumaraswamy-G class with three extra positive parameters, which generalizes the Cordeiro and de Castro's family. Some special distributions in the new class are discussed. We derive some mathematical properties of the proposed class including explicit expressions for the quantile function, ordinary and incomplete moments, generating function, mean deviations, reliability, Rényi entropy and Shannon entropy. The method of maximum likelihood is used to fit the distributions in the proposed class. Simulations are performed in order to assess the asymptotic behavior of the maximum likelihood estimates. We illustrate its potentiality with applications to two real data sets which show that the extended Weibull model in the new class provides a better fit than other generalized Weibull distributions.

Alternanthera brasiliana (L.) Kuntze is recognized for its healing properties; however, its therapeutic effects remain unclear. Therefore, our study aimed to elucidate the wound healing activities of A. brasiliana using in vitro and in vivo assays. In vitro assays were used to evaluate the antibacterial, anti-inflammatory, and antioxidant effects of A. brasiliana extract. For the in vivo study, two dorsal excisions were established in Wistar rats using a punch (1.5 cm in diameter), which were topically treated daily with 2% carbopol gel (Ctrl group) or 20% hydroalcoholic plant extract with 2% carbopol gel (A. brasiliana–Ab group). After the 2nd, 7th, 14th, and 21st days, inflammation, oxidative damage, antioxidants, angiogenesis, tissue formation, and re-epithelialization were evaluated. In vitro, Ab reduced nitric oxide, anion superoxide, and pro-inflammatory cytokine production. In vivo, Ab presented lower levels of inflammatory infiltrate, although increased levels of IL-1β and TGF-β1 were observed. The plant extract controlled oxidative damage by antioxidants, which favored angiogenesis, collagenesis, and wound re-epithelialization. Thus, the topical application of the hydroalcoholic extract of 20% A. brasiliana was distinguished by its important anti-inflammatory and antioxidant activities both in vivo and in vitro. The plant extract also stimulated angiogenesis and tissue formation, accelerating total re-epithelization, which is promising for wound healing.

Healing is the process responsible for restoring the integrity of the body's internal or external structures when they rupture. Photobiomodulation (PBM) stands out as one of the most efficient resources in the treatment of epithelial lesions, as well as hyaluronic acid (HA), which has been emerging as a new molecule for the treatment of dermal and epidermal lesions. The biological application of gold nanoparticles (GNPs) shows promising results. This study aimed to investigate the possible anti-inflammatory and antioxidant effects of the association between PBM and GNPs-linked HA in an epithelial lesion model. Fifty Wistar rats were randomly distributed in the Control Group (CG); (PBM); (PBM + HA); (PBM + GNPs); (PBM + GNPs-HA). The animals were anesthetized, trichotomized, and induced to a surgical incision in the dorsal region. Topical treatment with HA (0.9%) and/or GNPs (30 mg/kg) occurred daily associated with 904 nm laser irradiation, dose of 5 J/cm2, which started 24 h after the lesion and was performed daily until the seventh day. The levels of proinflammatory (IL1 and TNFα), anti-inflammatory (IL10 and IL4) and growth factors (FGF and TGFβ) cytokines and oxidative stress parameters were evaluated, besides histological analysis through inflammatory infiltrate, fibroblasts, new vessels, and collagen production area. Finally, for the analysis of wound size reduction, digital images were performed and subsequently analyzed by the IMAGEJ software. The treated groups showed a decrease in proinflammatory cytokine levels and an increase in anti-inflammatory cytokines. TGFβ and FGF levels also increased in the treated groups, especially in the combination therapy group (PBM + GNPs-HA). Regarding the oxidative stress parameters, MPO, DCF, and Nitrite levels decreased in the treated groups, as well as the oxidative damage (Carbonyl and Thiol groups). In contrast, antioxidant defense increased in the groups with the appropriate therapies proposed compared to the control group. Histological sections were analyzed where the inflammatory infiltrate was lower in the PBM + GNPs-HA group. The number of fibroblasts was higher in the PBM and PBM + HA treated groups, whereas collagen production was higher in all treated groups. Finally, in the analysis of the wound area contraction, the injury group presented a larger area in cm2 compared to the other groups. Taken together, these results allow us to observe that the combination of PBM + GNPs-HA optimized the secretion of anti-inflammatory cytokines, proliferation and cell differentiation growth factors, and made an earlier transition to the chronic phase, contributing to the repair process.

Cardiovascular diseases affect a large part of the population during adulthood. Several epidemiological and experimental studies have demonstrated an association between maternal protein restriction and a marked risk of developing heart disease during early intrauterine and postnatal life. Maternal nutritional conditions act by modulating the microenvironment, thus favoring adaptive processes of the fetal organism for development to occur. However, the physiological profile is established in this period and its effects can be observed in the long term. In the present study, the cardiac muscles of 15-day-old offspring of Wistar rats subjected to maternal protein restriction during pregnancy and/or lactation were evaluated to identify possible cardiac changes relevant for heart disease in adulthood. The offspring of restricted female rats during pregnancy had a lower birth weight. Male offspring subjected to restriction during pregnancy and lactation showed an increase in the concentration of H

Obesity in menopausal women occurs because of the systemic effects of loss of ovarian function, resulting in increased body weight and oxidative stress. Caloric restriction (CR) is essential for weight loss, since it provides benefits associated with metabolic normalization resulting from the action of sirtuins. The aim of this work was to evaluate the physiological effects of weight cycling in ovariectomized females. Females aged 2 mo ( n = 8/group) were submitted to simulated surgery, ovariectomy (OVX group), and ovariectomy with weight fluctuation (WF group). In the WF group, weight cycling was performed two times, using 21 days of ad libitum commercial feed and 21 days of caloric restriction with 40% of the feed consumed by the OVX group. After 17 wk, the animals were evaluated experimentally. Weight fluctuations reduced triacylglycerol and the adipose tissue index of the WF animals, while increasing the expression of antioxidant proteins. In addition to causing fluctuations in the physiological parameters, the weight cycling led to increases of adipocyte number and serum fatty acids. These effects were reflected in increased expression of the sirtuin (SIRT) 1 and SIRT4 proteins, as well as protein complexes of the mitochondrial electron transport chain, especially in the liver and adipose tissues. The weight-cycling results suggested that mitochondrial and nuclear sirtuins were active in cellular signaling for the control of lipid metabolism, oxidative phosphorylation, and redox status. Weight cycling was able to restore the health characteristics of lean animals.

Nicotinamide adenine dinucleotide (NAD)+ precursors such as nicotinamide activate sirtuins and enhance energy metabolism. The aim of this study was to evaluate the metabolic effects of nicotinamide in ovariectomized (OVX) female rats to establish molecular targets against obesity, which support the safe therapeutic application of nicotinamide. The OVX animals were divided into groups: SHAM (simulated surgery), SHAMn (two weeks of 35 mg·kg–1 nicotinamide per day, by gavage), OVX, and OVXn (two weeks of 35 mg·kg–1 nicotinamide per day, by gavage). The results indicated that nicotinamide favored lipolysis, as evidenced by an increase in free fatty acid and hepatic triglyceride levels, which were not fully normalized during the treatment period. The lipolysis appeared to be due to increased SIRT1 and mitochondrial oxidative phosphorylation in muscle and adipose tissue. There were decreases in muscle and fat nicotinamide N-methyltransferase (NNMT), which were associated with decreases in mass and triglyceride, low-density lipoprotein cholesterol (LDLc), and total cholesterol content. Nicotinamide appeared to be beneficial for the glycemic profile, with normal hepatic glycogen storage and a tendency towards insulin sensitivity in the OVXn. In the SHAMn group, nicotinamide led to glucose intolerance, together with reduced muscle expressions of nicotinamide phosphoribosyltransferase (NAMPT) and SIRT3, suggesting that there were no short-term benefits. Supplementation with nicotinamide led to tissue-specific adaptive lipid and molecular changes in OVX rats.

Percutaneous collagen induction (PCI) is an alternative treatment for skin dysfunctions, it aims to stimulate collagen production by encouraging normal wound healing that occurs after any trauma by inducing microlesions; also it may be potentiated with the association with drugs such as hyaluronic acid (HA). Our objective was to evaluate the effects of PCI associated with hyaluronic acid (0.9%) on inflammatory process, oxidative stress, and collagen production in rat epidermis. For the study, 36 adult Wistar rats were randomly divided into 6 groups (n = 6): Control; PCI 0.5; PCI 1.0; HA; PCI 0.5 + HA; and PCI 1.0 + HA. The animals were anesthetized, trichotomized, and the application of therapies was performed once; After 7 days, the animals were euthanized for removal of the skin region. Levels of pro-inflammatory (IL1, IL6, TNFα), anti-inflammatory (IL4 and IL10) cytokines and growth factors (FGF, TGFβ) were evaluated, besides oxidative stress parameters and histological analysis. In combination groups, there is a decrease in TNFα compared with the control and PCI groups in contrast to a significant increase in anti-inflammatory cytokines and growth factors. Oxidant and oxidative damage levels showed a significant decrease in PCI + HA groups in relation to PCI groups while antioxidant defense increased in PCI + HA groups compared with the control group. The number of fibroblasts was increased in the PCI 1.0 group in relation to the control, HA, and PCI 0.5. The number of blood vessels and collagen area was increased in groups PCI and PCI + HA compared with the HA group. We conclude that the combination of PCI with HA is able to accelerate the acute inflammatory process, reducing its deleterious effects and anticipating the chronic response, contributing to tissue repair.

Purpose: To evaluate the healing potential of the electrospinning membranes of Poly (Lactic Acid) (PLA) associated with Sedum dendroideum extract in burn injuries in rats. Methods: Seventy-five rats were submitted to burn injury on their back skin: (C) untreated; (F) with daily topical application of S. dendroideum extract; (M) with electrospinning membranes of PLA; (MF10) with electrospinning membranes of PLA with 10% S. dendroideum extract; (MF25) with electrospinning membranes of PLA with 25% S. dendroideum extract. Tissue samples were taken after 2, 6 and 14 days of the burn injury and were subjected to histomorfometric analysis of quantification of fibroblasts, collagen fibers, blood vessels, and inflammatory infiltrate Results: The histomorphometric analysis showed an increase in the number of fibroblasts, collagen fibers and blood vessels in the burns treated with membranes of PLA, associated or not with the 10% and 25% extract. The extract of S. dendroideum promoted the increase of collagen fibers. Conclusion: The electrospinning PLA membrane, isolated or associated with the S. dendrodeum extract, favored the healing of burn injuries in this experimental model, with an increase of fibroblasts, collagen fibers, and blood vessels. S. dendroideum isolated only stimulated the collagenesis.

The objective of this study was to evaluate the effects of red Light Emiting Diode (red LED) irradiation on fibroblasts in adipose-derived mesenchymal stem cells (ASC) co-culture on the scratch assay. We hypothesized that red LED irradiation could stimulate paracrine secretion of ASC, contributing to the activation of genes and molecules involved in cell migration and tissue repair. ASC were co-cultured with NIH/3T3 fibroblasts through direct contact and subjected to red LED irradiation (1.45 J/cm2/5min6s) after the scratch assay, during 4 days. Four groups were established: fibroblasts (F), fibroblasts + LED (FL), fibroblasts + ASC (FC) and fibroblasts + LED + ASC (FLC). The analyzes were based on Ctgf and Reck expression, quantification of collagen types I and III, tenomodulin, VEGF, TGF-β1, MMP-2 and MMP-9, as well as viability analysis and cell migration. Higher Ctgf expression was observed in FC compared to F. Group FC presented higher amount of tenomodulin and VEGF in relation to the other groups. In the cell migration analysis, a higher number of cells was observed in the scratched area of the FC group on the 4th day. There were no differences between groups considering cell viability, Reck expression, amount of collagen types I and III, MMP-2 and TGF-β1, whereas TGF-β1 was not detected in the FC group and the MMP-9 in none of the groups. Our hypothesis was not supported by the results because the red LED irradiation decreased the healing response of ASC. An inhibitory effect of the LED irradiation associated with ASC co-culture was observed with reduction of the amount of TGF-β1, VEGF and tenomodulin, possibly involved in the reduced cell migration. In turn, the ASC alone seem to have modulated fibroblast behavior by increasing Ctgf, VEGF and tenomodulin, leading to greater cell migration. In conclusion, red LED and ASC therapy can have independent effects on fibroblast wound healing, but the combination of both does not have a synergistic effect. Therefore, future studies with other parameters of red LED associated with ASC should be tested aiming clinical application for tissue repair., Biological sciences; Cell biology; Proteins; Biomedical engineering; Molecular biology; Regenerative medicine; Scratch assay; Ctgf; TGF-β1; Tenomodulin; Repair; Cell migration

The limitations of bone reconstruction techniques have stimulated the tissue engineering for the repair of large bone defects using osteoconductive materials and osteoinductive agents. This study evaluated the effects of low intensity electric current on the inorganic bovine graft in calvaria defects. Bone defects were performed with piezoelectric system in the calvaria of Wistar rats divided into four groups (n = 24): (C) without grafting and without electrical stimulation; (E) with grafting; (MC) without grafting and submitted to electrical stimulation; (MC + E) with grafting and submitted to electrical stimulation. Inflammatory, angiogenic and osteogenic events during bone repair at the 10th, 30th, 60th, and 90th days were considered. Several inflammatory markers demonstrated the efficacy of grafting in reducing inflammation, particularly when subjected to electrical stimulation. Angiogenesis and collagen organization were more evident by electrical stimulation application on the grafts. Moreover, the osteogenic cell differentiation process indicated that the application of microcurrent on grafting modulated the homeostasis of bone remodeling. It is concluded that microcurrent favored the performance of grafts in calvarial rat model. Low-intensity electrical current might improve the osteoconductive property of grafting in bone defects. Therefore, electrical current becomes an option as complementary therapy in clinical trials involving bone surgeries and injuries. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 924-932, 2019.

Additive manufactured scaffolds are widely used as 3D support structures for tissue engineering. This paper investigates the mechanisms behind bone regeneration due to the combined use of 3D printed poly (ϵ-caprolactone)/graphene (PCL/G) electro-active scaffolds and electrical stimulation. A comprehensive in vivo study was conducted to assess the proposed approach, using a rat model. Results show that the combined use of electro-active scaffolds and electrical stimulation therapy accelerates the bone regeneration process and the formation of more organized new bone, through fast angiogenesis, and a rapid transition to the mineralization and bone remodelling phase. The mechanism is investigated and explained.

Made available in DSpace on 2022-04-29T08:30:18Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-09-01 Objective: To evaluate formulations of 1 % silver (Ag) nanoparticles for treating traumatic lesions induced in the oral mucosa of rats, because these lesions are commonly observed in the dental clinic, and their therapeutic forms are scarce. Methods: Wistar rats were punch-injured (two circular fragments, 4.0 mm in diameter) in the oral mucosa (one on each side), and were treated topically (twice per week) with the treatments/groups including: no injury, control, vehicle, diluted Ag, soluble Ag, and solid Ag. On the 2nd, 7th, and 14th days postinjury, biopsies were collected for immunohistochemistry and biochemical analysis. Results: The group diluted Ag revealed a higher level of inflammatory infiltrate on the 2nd day, whereas solid Ag presented lower levels. The Ag solid group presented higher IL-1β on the 2nd day and increased IL-10 and TGF-β1 throughout the follow-up. Moreover, all three Ag groups presented lower levels of oxidative stress markers and, on the 7th day, the diluted Ag and solid Ag groups revealed higher antioxidants. Diluted Ag and soluble Ag groups presented greater blood vessels proliferation, whereas soluble Ag and solid Ag groups revealed greater VEGF on the 2nd and 14th days. Furthermore, all three Ag groups were highlighted during fibroplasia, although collagenesis was similar to that observed in the control group. Conclusions: Although diluted Ag was noticeable for its important angiogenesis and fibroplasia, solid Ag was the most suitable formulation in healing oral lesions as it efficiently controlled inflammation and oxidative stress, thus favoring angiogenesis and tissue formation. Graduate Program in Biomedical Sciences University Center of Herminio Ometto Foundation – FHO, Dr. Maximiliano Baruto Ave, 500. Jardim Universitario Laboratory of Magnetic Materials and Colloids Department of Physical Chemistry Institute of Chemistry Sao Paulo State University (UNESP), Prof. Francisco Degni Ave, 55. Jardim Quitandinha Laboratory of Experimental Physiopathology Graduate Program in Science of Health Universidade do Extremo Sul Catarinense - UNESC, Universitaria Ave, 1105. Universitario, Bloco S - Room 017 Graduate Program in Odontology University Center of Herminio Ometto Foundation – FHO, Dr. Maximiliano Baruto Ave, 500. Jardim Universitario Laboratory of Magnetic Materials and Colloids Department of Physical Chemistry Institute of Chemistry Sao Paulo State University (UNESP), Prof. Francisco Degni Ave, 55. Jardim Quitandinha

Introduction This study aimed to assess the anti-inflammatory and antimicrobial effects of mouthwashes with 0.12% chlorhexidine (CLX) and 0.5% Zingiber officinale essential oil (ZOEO). Methods The gas chromatography-mass spectrometry of ZOEO was developed, and the mouthwash was prepared. Thirty-one adult subjects of both sexes with fixed orthodontic appliances were selected. For 7 days, the mouthwashes with CLX, ZOEO, and flavored sterile water placebo were used randomly, with a 15-day interval between each solution. Saliva was collected before the first mouthwash, 1 minute and 15 minutes after it, and on the seventh day. The patients were subjected to clinical examinations of the bonded bracket index proposed by Ciancio, bleeding on probing, and sensory analysis (flavor). Generalized linear models were used to assess in vitro cell viability. The GENMOD procedure was used to assess the changes of bleeding on probing, and Friedman and Wilcoxon tests were used for data on colony-forming units per milliliter (CFU/mL), bonded bracket index, and flavor, at the 5% significance level. Results In the microbiologic analysis, the ZOEO mouthwash presented antimicrobial effectiveness for Streptococcus mutans as well as the CLX mouthwash, but it did not show the same substantivity. The ZOEO was efficient in controlling dental biofilm and reducing gingival bleeding. The sensory analyses showed that the flavor for ZOEO and CLX solutions presented low acceptability. Conclusions The ZOEO mouthwash has an anti-inflammatory property with an effect on reducing gingival bleeding. However, it requires adjustments to the formulation to improve flavor quality.

We investigated the structural and functional adaptations of the pancreas during weight cycling in animals submitted to hypoestrogenism. Female Wistar rats were distributed among the following test groups: ShamAL (AL, ad libitum); OVXAL (ovariectomized); and OVXcycle (dietary restriction with weight cycling). The ShamAL and OVXAL groups received commercial feed ad libitum, whereas the OVXcycle group received 21 days of commercial feed ad libitum, and 21 days of caloric restriction, with caloric intake amounting to 40% of the amount of feed consumed by the rats in the OVXAL group. The tolerance tests for glucose and insulin were applied. After euthanasia, the pancreas and adipose tissue were collected. The disappearance of glucose during the insulin assay occurred at a higher rate in tissues from the OVXcycle group, compared with the OVXAL group. Fasting glycemia and perirenal adipose tissue were lower in the OVXcycle group. By comparison with the ShamAL and OVXAL groups, the OVXcycle group showed higher protein expression of the M1 and M3 receptors and SOD1–2, as well as higher carbachol-induced insulin secretion. Under highly stimulatory conditions with 16.7 mmol/L glucose, the OVXAL and OVXcycle groups presented lower insulin secretion compared with the ShamAL group. Morphological analysis revealed higher iron deposition in the OVXAL islets by comparison with the OVXcycle group. These results show that ovariectomy accelerated the loss of pancreatic islet function, and that weight cycling could restore the function of the islets.

Crotamine is a single-chain polypeptide with cell-penetrating properties, which is considered a promising molecule for clinical use. Nevertheless, its biosafety data are still scarce. Herein, we assessed the in vivo proinflammatory properties of crotamine, including its local effect and systemic serum parameters. Sixty male Wistar rats were intradermically injected with 200, 400 and 800 &micro, g crotamine and analyzed after 1, 3 and 7 days. Local effect of crotamine was assessed by determination of MPO and NAG activities, NO levels and angiogenesis. Systemic inflammatory response was assessed by determination of IL-10, TNF-&alpha, CRP, NO, TBARS and SH groups. Crotamine induced macrophages and neutrophils chemotaxis as evidenced by the upregulation of both NAG (0.5&ndash, 0.6 OD/mg) and MPO (0.1&ndash, 0.2 OD/mg) activities, on the first and third day of analysis, respectively. High levels of NO were observed for all concentrations and time-points. Moreover, 800 &mu, g crotamine resulted in serum NO (64.7 &mu, M) and local tissue NO (58.5 &mu, M) levels higher or equivalent to those recorded for their respective histamine controls (55.7 &mu, M and 59.0 &mu, M). Crotamine also induced a significant angiogenic response compared to histamine. Systemically, crotamine induced a progressive increase in serum CRP levels up to the third day of analysis (22.4&ndash, 45.8 mg/mL), which was significantly greater than control values. Crotamine (400 &mu, g) also caused an increase in serum TNF-&alpha, in the first day of analysis (1095.4 pg/mL), however a significant increase in IL-10 (122.2 pg/mL) was also recorded for the same time-point, suggesting the induction of an anti-inflammatory effect. Finally, crotamine changed the systemic redox state by inducing gradual increase in serum levels of TBARS (1.0&ndash, 1.8 &mu, M/mL) and decrease in SH levels (124.7&ndash, 19.5 &mu, M/mL) throughout the experimental period of analysis. In summary, rats intradermally injected with crotamine presented local and systemic acute inflammatory responses similarly to histamine, which limits crotamine therapeutic use on its original form.

The repair process consists of molecular and cellular events that can be accelerated by specific therapies. Considering this, the objective of this study was to evaluate the effects of ibuprofen phonophoresis associated with gold nanoparticles in the animal model of traumatic muscle injury. Was used 80 male wistar rats divided into eight groups: Sham; Muscle injury (MI); MI + therapeutic pulsed ultrasound (TPU); MI + Ibuprofen (IBU); MI + GNPs; MI + TPU+ IBU; MI + TPU + GNPs and MI + TPU + IBU + GNPs. The lesion in the gastrocnemius was performed by a single direct trauma impact on the injured press. The animals were treated with pulsed ultrasound and the gel with gold nanoparticles and/or ibuprofen. The treatment was applied daily for 5 days and the first session was 12 h after the muscle injury. The gastrocnemius muscle was surgically removed for analyzes biochemical, molecular and histological. In the analyzes only the MI + TPU + IBU + GNPs group showed a reduction in TNF-a and IL-1 levels, with a concomitant increase in the levels of anti-inflammatory cytokines. In the analysis of oxidative stress, only the MI + TPU + IBU + GNPs group presented a reversal of the condition when compared to the MI group. In the histological analysis, the MI group presented a large cell infiltrate and a centralized nucleus and only the MI + TPU + IBU + GNPs group showed a structural improvement, also in the pain results the MI + TPU + IBU + GNPs showed a significant difference in comparison to the MI group (p0.01). We believe that the effects of phonophoresis with anti-inflammatory drugs associated with gold nanoparticles may potentiate the reduction of the inflammatory response and regulate the cellular redox state.

A cicatrização de feridas é uma resposta biológica à lesão tecidual. Inúmeras pesquisas e diversos métodos estão sendo desenvolvidos e empregados para acelerar o processo de cicatrização. A utilização de fitoterápicos tem merecido crescente interesse, assim, a presente revisão faz uma descrição das perspectivas na utilização de fitoterápicos na cicatrização tecidual. A pesquisa foi realizada a partir de uma revisão da literatura especializada, sendo consultados artigos científicos publicados entre os anos de 1996 e 2016. Empresas e pesquisadores de diferentes áreas do conhecimento e a população em geral têm demonstrado interesse nos fitoterápicos como alternativas para o tratamento de diversas afecções e lesões. Este fato ocorre principalmente pelo menor custo e a possibilidade de menores efeitos adversos dos fitoterápicos em comparação aos medicamentos alopáticos, assim como, pela biodiversidade da flora brasileira.Descritores: Medicamentos Fitoterápicos; Cicatrização; Ferimentos e Lesões.

Made available in DSpace on 2019-10-04T12:32:46Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-01-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Herminio Ometto Foundation Introduction: Periodontitis is characterized by inflammatory mediators beyond T lymphocyte function and phenotype (Thl/Th2/Th17). The clinical diversity in periodontitis makes it difficult to characterize the immune response in patients. This study evaluated the profile of the adaptive immune response in the periodontal disease model. Methods: 72 rats (Wistar) were divided into a control group (CTL/day 0) and periodontitis (PD15/15 days and PD60/60 days). In the PD15 and PD60 groups, periodontal disease was induced by ligature with a silk thread placed in the cervical region of the upper first molar. After euthanasia, the periodontal tissue was analyzed by flow cytometry (CD4, CD8, CD25, CD44), semi-quantitative RT-PCR (T-bet, GATA-3, ROR gamma t), semi-quantitative RT-PCR and ELISA IFN-gamma, TNF-alpha, IFN-gamma, IL-4, IL-6, IL-10, IL-17) and by Western blotting (Caspase-9, PCNA). Results: The number of CD4(+) CD25(+), CD4(+) CD44(+), CD8(+) CD25(+) and CD8(+) CD44(+) cells and expression levels of T-bet and GATA-3 are increased in the PD60 group compared to PD15 and CTL. The ROR gamma-t gene transcript increased in the PD15 group in relation to PD60 and CTL. The cytokines IFN-gamma, TNF-alpha and IL-17 increased in the PD60 group in relation to PD15. The expression of Caspase-9 was higher in the PD60 group than in PD15. Conclusions: The results suggest that the evolution of gingivitis to periodontitis is related to the accumulation of activated Thl cells (IFN-gamma and TNF-alpha) associated with the presence of increased IL-17. Studies with inhibitors of these cytokines in periodontal disease may lead to therapy directed at blocking the inflammatory process in this pathology, interrupting bone loss. Ctr Univ Herminio Ometto UNIARARAS, Grad Program Biomed Sci, Araras, SP, Brazil Ctr Univ Herminio Ometto UNIARARAS, Grad Program Odontol, Araras, SP, Brazil Sao Paulo State Univ, Dept Diag & Surg, Sch Dent, Araraquara, SP, Brazil Univ Estadual Campinas, Inst Biol, Dept Genet Evolut & Bioagents, Campinas, SP, Brazil Sao Paulo State Univ, Dept Diag & Surg, Sch Dent, Araraquara, SP, Brazil FAPESP: 2012-51110-8

Wound healing studies are intricate, mainly because of the multifaceted nature of the wound environment and the complexity of the healing process, which integrates a variety of cells and repair phases, including inflammation, proliferation, reepithelialization and remodelling. There are a variety of possible preclinical models, such as in mice, rabbits and pigs, which can be used to mimic acute or impaired for example, diabetic and nutrition-related wounds. These can be induced by many different techniques, with excision or incision being the most common. After determining a suitable model for a study, investigators need to select appropriate and reproducible methods that will allow the monitoring of the wound progression over time. The assessment can be performed by non-invasive protocols such as wound tracing, photographic documentation (including image analysis), biophysical techniques and/or by invasive protocols that will require wound biopsies. In this article, we provide an overview of some of the most often needed and used: (a) preclinical/animal models including incisional, excisional, burn and impaired wounds; (b) methods to evaluate the healing progression such as wound healing rate, wound analysis by image, biophysical assessment, histopathological, immunological and biochemical assays. The aim is to help researchers during the design and execution of their wound healing studies.

BACKGROUND: Various studies have shown that phototherapy promotes the healing of cutaneous wounds. OBJECTIVE: To investigate the effect of phototherapy on healing of cutaneous wounds in nourished and undernourished rats. METHODS: Forty rats, 20 nourished plus 20 others rendered marasmus with undernourishment, were assigned to four equal groups: nourished sham, nourished Light Emitting Diode treated, undernourished sham and undernourished Light Emitting Diode treated. In the two treated groups, two 8-mm punch wounds made on the dorsum of each rat were irradiated three times per week with 3 J/cm2 sq cm of combined 660 and 890nm light; wounds in the other groups were not irradiated. Wounds were evaluated with digital photography and image analysis, either on day 7 or day 14, with biopsies obtained on day 14 for histological studies. RESULTS: Undernourishment retarded the mean healing rate of the undernourished sham wounds (p < 0.01), but not the undernourished Light emission diode treated wounds, which healed significantly faster (p < 0.001) and as fast as the two nourished groups. Histological analysis showed a smaller percentage of collagen in the undernourished sham group compared with the three other groups, thus confirming our photographic image analysis data. CONCLUSION: Phototherapy reverses the adverse healing effects of undernourishment. Similar beneficial effects may be achieved in patients with poor nutritional status.

Diabetes can cause serious health complications, which can affect every organ of the body, including the skin. The molecular etiology has not yet been clarified for all diabetic skin conditions. Thus, this study aimed to investigate the changes of diabetes in skin compared to non-diabetic skin in rats. Fifteen days after establishing the diabetic status, skin samples from the dorsum-cervical region were harvested for subsequent analysis of alterations caused by diabetes. Our results demonstrate that diabetes stimulated higher inflammation and oxidative stress in skin, but antioxidant defense levels were lower compared to the non-diabetic group (p

The purpose of this study was to evaluate the efficacy of chitosan-alginate membrane to accelerate wound healing in experimental cutaneous wounds. Two wounds were performed in Wistar rats by punching (1.5 cm diameter), treated with membranes moistened with saline solution (CAM group) or with saline only (SL group). After 2, 7, 14, and 21 days of surgery, five rats of each group were euthanized and reepithelialization was evaluated. The wounds/scars were harvested for histological, flow cytometry, neutrophil infiltrate, and hydroxyproline analysis. CAM group presented higher inflammatory cells recruitment as compared to SL group on 2(nd) day. On the 7(th) day, CAM group showed higher CD11b(+) level and lower of neutrophils than SL group. The CAM group presented higher CD4(+) cells influx than SL group on 2(nd) day, but it decreased during the follow up and became lower on 14(th) and 21(st) days. Higher fibroplasia was noticed on days 7 and 14 as well as higher collagenesis on 21(st) in the CAM group in comparison to SL group. CAM group showed faster reepithelialization on 7(th) day than SL group, although similar in other days. In conclusion, chitosan-alginate membrane modulated the inflammatory phase, stimulated fibroplasia and collagenesis, accelerating wound healing process in rats.

This paper presents a mechanism to provide a real-time assessment of voice quality on mobile handled devices. This solution considers the voice degradations caused by the radio frequency channel and packet losses on the IP network. Furthermore, the network architecture of the proposed solution is introduced and the application is implemented on the user mobile device.

A cicatrização de feridas é uma resposta biológica à lesão tecidual sendo que diversos métodos terapêuticos estão sendo desenvolvidos e empregados para acelerar tal processo. Entre esses se observa a utilização de estimulação elétrica de baixa intensidade que favorece numerosos eventos no processo cicatricial assim como estimula eventos celulares, a circulação local e também promove alívio de quadros dolorosos. Sua aplicação é subsensorial não causando dor e/ou desconforto. Efeitos colaterais não são observados constituindo uma técnica de baixo custo e não invasiva. O presente estudo descreve a utilização da microcorrente (MC) como método não farmacológico no processo de reparo tecidual. Para isso foi realizada revisão da literatura, sendo consultados artigos científicos localizados nas bases de dados Medline, Scielo, Lilacs, portal de Periódicos CAPES e GoogleAcadêmico, publicados entre os anos de 1997 e 2014. Conclui-se que a MC é uma técnica inovadora e eficiente, podendo ser usada de forma isolada ou associada a outros métodos físicos ou a curativos visando à reparação tecidual, diminuição da inflamação, dor, podendo ser utilizada na melhoria da qualidade de vida.Descritores: Condutas Terapêuticas; Terapia por Estimulação Elétrica; Cicatrização.

Ethnopharmacological relevance Struthanthus vulgaris (Vell.) Mart. (Loranthaceae) has been largely used in traditional folk medicine in Brazil as an anti-inflammatory agent and to treat various skin disorders, including wounds. Aims of the study To investigated the influence of 5% Struthanthus vulgaris ointment during cutaneous wound healing in rats. Materials and methods Twenty Wistar rats were used in each group according the daily treatment, S. vulgaris 5% ointment (SV 5%) and vehicle control groups. Four full thicknesses wounds were punched in back side skin of each animal, and five animals were sacrificed after 2, 7, 14 and 21 days after surgery for histological, immunological and biochemical analysis. Results A significant wound closured area in the S. vulgaris 5% group of about 38% and 35% as compared to 19% and 21% in the control group was observed after 2 and 5 days, respectively. Histological and biochemical analysis of the skin biopsies showed that S. vulgaris treated wounds exhibited increased granulation tissue and regulated the inflammatory response by modulating the release of pro and anti-inflammatory cytokines like IL-1α, TNF-α and IL-10, nitric oxide and, growth factors like TGF-β. Moreover, S. vulgaris showed a marked and robust increase in the deposition and organization of collagen fibers in the wounds, and improve the quality of the scar tissue. Conclusions Altogether these data revealed that S. vulgaris seems to prevent an over expression of inflammation and accelerates wound epithelialization and might be beneficial for treating healing disorders.

In a previous study, we performed the chemical characterization of a polyvinyl alcohol (PVA) membrane supplemented with latex proteins (LP) displaying wound healing activity, and its efficacy as a delivery system was demonstrated. Here, we report on aspects of the mechanism underlying the performance of the PVA-latex protein biomembrane on wound healing. LP-PVA, but not PVA, induced more intense leukocyte (neutrophil) migration and mast cell degranulation during the inflammatory phase of the cicatricial process. Likewise, LP-PVA induced an increase in key markers and mediators of the inflammatory response (myeloperoxidase activity, nitric oxide, TNF, and IL-1β). These results demonstrated that LP-PVA significantly accelerates the early phase of the inflammatory process by upregulating cytokine release. This remarkable effect improves the subsequent phases of the healing process. The polyvinyl alcohol membrane was fully absorbed as an inert support while LP was shown to be active. It is therefore concluded that the LP-PVA is a suitable bioresource for biomedical engineering.