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There are several reasons for skin damage, including genetic factors, disorders, acute trauma, hard-to-heal wounds, or surgical interventions. Whatever the cause, wounds have a substantial impact on people who experience them, their caregivers and the healthcare system. Advanced wound care products have been researched and developed, providing an opportunity for faster and more complete healing. Tissue engineering (TE) is a promising strategy that can overcome limitations when choosing a graft for a wound. Amniotic membrane is a highly abundant, readily available, and inexpensive biological tissue that does not raise ethical concerns, with many applications in different fields of TE and regenerative medicine. It has attractive physical characteristics, such as elasticity, rigidity and mechanical strength, among others. The effects can also be potentiated by association with other substances, such as hyaluronic acid and growth factors. This paper describes new perspectives involving the use of amniotic membranes.
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Âmnio , Engenharia Tecidual , Cicatrização , Humanos , Âmnio/transplante , Ferimentos e Lesões/terapia , Medicina Regenerativa/métodosRESUMO
Cost-effective strategies for the treatment of chronic wounds must be developed. The green synthesis of gold nanoparticles (GNPs) it is possible to guarantee a lower toxicity in biological tissues and greater safety of applicability, in addition to adding the effects of nanoparticles (NPs) to those of extracts. The objective of this study was to evaluate the effects of treatment with biosynthesized GNPs in a chronic wound model. Wistar rats were distributed into 7 groups: Acute Wound (AW); Chronic wound (CW); CW + GNPs-Açaí; CW + GNPs-DB; CW + AV-GNPs; CW + SafGel®; CW + 660 nm laser. The chronic injury model was induced with topically applied Resiquimod for 6 days. Treatments were then initated on the fourteenth day after the last application of Resiquimod and carried out daily for ten days. The proposed therapies with GNPs were able to significantly reduce the inflammatory score and increase the rate of wound contraction. In histology, there was a reduction in the inflammatory infiltrate and increased gene expression of fibronectin and type III collagen, mainly in the CW + AV-GNPs group. The therapies were able to reduce pro-inflammatory cytokines, increase anti-inflammatory cytokines, and reduce oxidative stress. The results demonstrated that the effects of GNPs appear to complement those of the extracts, thereby enhancing the tissue repair process.
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PURPOSE: Bacterial cellulose (BC) has shown high capacity for the treatment of wounds and burns, providing a moisty environment. Calcium alginate can be associated with BC to create gels that aid in wound debridement and contribute to appropriate wound healing. This study is aimed at characterizing and evaluating the use of bacterial cellulose/alginate gel in skin burns in rats. METHODS: Cellulose and cellulose/alginate gels were compared regarding the capacity of liquid absorption, moisture, viscosity, and potential cytotoxicity. The 2nd degree burns were produced using an aluminum metal plate (2.0cm) at 120ºC for 20s on the back of rats. The animals were divided into non-treated, CMC(Carboxymethylcellulose), Cellulose(CMC with bacterial cellulose), and Cellulose/alginate(CMC with bacterial cellulose and alginate). The animals received topical treatment 3 times/week. Biochemical (MPO, NAG and oxidative stress), histomorphometry and immunohistochemical assays (IL-1ß IL-10 and VEGF) were conducted on the 14th, 21st, 28th, and 35th days. RESULTS: Cellulose/Alginate gel showed higher absorption capacity and viscosity compared to Cellulose gel, with no cytotoxic effects. Cellulose/alginate presented lower MPO values, a higher percentage of IL-10, with greater and balanced oxidative stress profile. CONCLUSIONS: The use of cellulose/alginate gel reduced neutrophils and macrophage activation and showed greater anti-inflammatory response, which can contribute to healing chronic wounds and burns.
Assuntos
Alginatos , Queimaduras , Celulose , Hidrogéis , Ratos Wistar , Cicatrização , Animais , Alginatos/uso terapêutico , Celulose/uso terapêutico , Queimaduras/tratamento farmacológico , Queimaduras/terapia , Cicatrização/efeitos dos fármacos , Hidrogéis/uso terapêutico , Masculino , Ratos , Ácido Glucurônico/uso terapêutico , Ácidos Hexurônicos/uso terapêutico , Reprodutibilidade dos Testes , Viscosidade , Estresse Oxidativo/efeitos dos fármacos , Imuno-Histoquímica , Fatores de Tempo , Pele/lesões , Pele/efeitos dos fármacosRESUMO
BACKGROUND: Tracheal grafts have been investigated for over a century, aiming to replace various lesions. However, tracheal reconstruction surgery remains a challenge, primarily due to anatomical considerations, intraoperative airway management, the technical complexity of reconstruction, and the potential postoperative morbidity and mortality. Due to research development, the amniotic membrane (AM) and Wharton's Jelly (WJ) arise as alternatives within the new set of therapeutic alternatives. These structures hold significant therapeutic potential for tracheal defects. This study analyzed the capacity of tracheal tissue regeneration after 60 days of decellularized WJ and AM implantation in rabbits submitted to conventional tracheostomy. METHODS: An in vivo experimental study was carried out using thirty rabbits separated into three groups (Control, AM, and WJ) (n = 10). The analyses were performed 60 days after surgery through immunohistochemistry. RESULTS: Different immunomarkers related to scar regeneration, such as aggrecan, TGF-ß1, and α-SMA, were analyzed. However, they highlighted no significant difference between the groups. Collagen type I, III, and Aggrecan also showed no significant difference between the groups. CONCLUSIONS: Both scaffolds appeared to be excellent frameworks for tissue engineering, presenting biocompatibility and a desirable microenvironment for cell survival; however, they did not display histopathological benefits in trachea tissue regeneration.
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The pathological manifestation of the inflammatory process primarily stems from the heightened release of pro-inflammatory cytokines, with IL-1ß standing out as a pivotal cytokine. The excessive presence of IL-1ß disrupts immune signaling, thereby assuming a pathogenic and exacerbating role in the pathophysiology of numerous inflammatory diseases. Regulating IL-1ß levels becomes crucial, and the IL-1Ra molecule serves this purpose by binding to the IL-1R1 receptor, thereby impeding the binding of IL-1ß. Several pharmaceuticals have entered the market, aiming to neutralize IL-1ß's biological function through diverse mechanisms. However, the existing IL-1ß inhibitors are recombinant proteins, characterized by a high production cost and limited stability. Therefore, this study aimed to predict a peptide, named DAP1-2, based on the IL-1Ra molecule. DAP1-2 was designed to attenuate responses triggered by IL-1ß by blocking the IL-1R1 receptor. The selection of amino acids from the IL-1Ra molecule (PDB: I1RA) that interact with the three domains of the IL-1R1 receptor was performed using Swiss PDB Viewer. After prediction, chemical synthesis was made using the Fmoc-Synthesis technique. The efficacy of DAP1-2 was assessed using RAW 264.7 cells, which were exposed to LPS (5 µg/mL) for 24 h to induce IL-1ß expression and treated with the peptides in different concentrations. IL-1ß levels were assessed using ELISA, and the gene expression of IL-1ß was measured by RT-qPCR, additionally to the viability test. Results revealed a significant reduction in IL-1ß levels and gene expression in cells stimulated by LPS and treated with DAP1-2 in different concentrations. Furthermore, the MTT assay confirmed the nontoxic nature of the peptides on the cell lineage. This alternative approach shows promise as an IL-1 inhibitor, due to the stability, ease of production, and cost-effectiveness provided by the use of synthetic peptides.
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Interleucina-1beta , Receptores Tipo I de Interleucina-1 , Interleucina-1beta/metabolismo , Animais , Camundongos , Receptores Tipo I de Interleucina-1/metabolismo , Receptores Tipo I de Interleucina-1/antagonistas & inibidores , Humanos , Peptídeos/farmacologia , Células RAW 264.7 , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Ligação Proteica , Lipopolissacarídeos/imunologiaRESUMO
Type 2 diabetes mellitus (T2D) is a metabolic disease, which occurs largely due to unhealthy lifestyle. As oxidative stress is believed to promote T2D, by inducing damage to lipids, proteins, and DNA, appropriate dietary interventions seem critical to prevent, manage, and even reverse this condition. Brazil nuts (Bertholletia excelsa, H.B.K.) are nature's richest source of selenium, a mineral that has shown several health benefits. Therefore, this study aims to assess the effects of selenium consumption, through Brazil nuts, on biochemical and oxidative stress parameters, and genomic instability in T2D patients. We recruited 133 patients with T2D, registered in the Integrated Clinics of the University of Southern Santa Catarina (Brazil). Participants consumed one Brazil nut a day for six months. Blood samples and exfoliated buccal cells were collected at the beginning and the end of the intervention. The glycemic profile, lipid profile, renal profile and hepatic profile, DNA damage and selenium content were evaluated. A total of 74 participants completed the intervention. Brazil nut consumption increased selenium and GSH levels, GPx, and CAT activity while DCF and nitrites levels decreased. Total thiols increased, and protein carbonyl and MDA levels decreased. Levels of baseline and oxidative DNA damage in T2D patients were significantly decreased, as well as the frequency of micronuclei and nuclear buds. The fasting glucose levels, HDL and LDL cholesterol, and GGT levels that increased significantly in patients with type 2 diabetes were significantly reduced with nut consumption. Our results show an increase in antioxidant activity, along with reductions of protein and lipid oxidation as well as DNA damage, suggesting that Brazil nut consumption could be an ally in reducing oxidative stress and modulating the genomic instability in T2D patients.
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Bertholletia , Diabetes Mellitus Tipo 2 , Selênio , Humanos , Bertholletia/química , Selênio/farmacologia , Sobrepeso , Diabetes Mellitus Tipo 2/genética , Mucosa Bucal , Lipídeos , Dano ao DNA , Instabilidade GenômicaRESUMO
Obesity results from an energy imbalance and has been considered an epidemic due to its increasing rates worldwide. It is classified as a low-grade chronic inflammatory disease and has associated comorbidities. Different nutritional strategies are used for the purpose of weight loss, highlighting low-carbohydrate (LC) diets, ketogenic diets, and intermittent fasting (IF). These strategies can lead to metabolic and behavioral changes as they stimulate different biochemical pathways. Therefore, this study evaluated memory, energy metabolism, neuroinflammation, oxidative stress, and antioxidant defense parameters in mice subjected to an LC diet, ketogenic diet (KD), or IF. Eighty male Swiss mice, 60 days old, were divided into 4 groups: control, LC, KD, or IF. Body weight was measured weekly, and food intake every 48 h. After 15 days of nutritional interventions, the animals were subjected to the behavioral object recognition test and subsequently euthanized. Then, visceral fat was removed and weighed, and the brain was isolated for inflammatory and biochemical analysis. We concluded from this study that the LC and KD strategies could damage memory, IF improves the production of adenosine triphosphate (ATP), and the LC, KD, and IF strategies do not lead to neuroinflammatory damage but present damage at the level of oxidative stress.
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Dieta Cetogênica , Estresse Oxidativo , Animais , Masculino , Camundongos , Estresse Oxidativo/fisiologia , Transtornos da Memória/metabolismo , Transtornos da Memória/etiologia , Doenças Neuroinflamatórias/metabolismo , Dieta com Restrição de Carboidratos , Jejum/metabolismo , Metabolismo Energético/fisiologia , Encéfalo/metabolismoRESUMO
Alzheimer's disease (AD) and depression are inflammatory pathologies, leading to increased inflammatory response and neurotoxicity. Therefore, this study aimed to evaluate the effect of the treatment with fluoxetine and/or galantamine and/or donepezil on the levels of proinflammatory and anti-inflammatory cytokines in a mixed animal model of depression and dementia. Adult male Wistar rats underwent chronic mild stress (CMS) protocol for 40 days and were subjected to stereotaxic surgery for intra-hippocampal administration of amyloid-beta (Aêµ) peptide or artificial cerebrospinal fluid (ACSF) to mimic the dementia animal model. On the 42nd day, animals were treated with water, galantamine, donepezil, and/or fluoxetine, orally for 17 days. On the 57th and 58th days, the Splash and Y-maze tests for behavior analysis were performed. The frontal cortex and hippocampus were used to analyze the tumor necrosis factor alfa (TNF-α), interleukin 1 beta (IL-1êµ), IL-6, and IL-10 levels. The results of this study show that animals subjected to CMS and administration of Aêµ had anhedonia, cognitive impairment, increased TNF-α and IL-1êµ levels in the frontal cortex, and reduced IL-10 levels in the hippocampus. All treatment groups were able to reverse the cognitive impairment. Only donepezil did not decrease the TNF-α levels in the hippocampus. Fluoxetine + galantamine and fluoxetine + donepezil reversed the anhedonia. Fluoxetine reversed the anhedonia and IL-1êµ levels in the frontal cortex. In addition, fluoxetine + donepezil reversed the reduction of IL-10 levels in the hippocampus. The results indicate a pathophysiological interaction between AD and depression, and the association of medications in the future may be a possible therapeutic strategy to reduce inflammation, especially the fluoxetine-associated treatments.
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Demência , Depressão , Modelos Animais de Doenças , Donepezila , Fluoxetina , Galantamina , Hipocampo , Ratos Wistar , Animais , Masculino , Fluoxetina/farmacologia , Fluoxetina/uso terapêutico , Donepezila/farmacologia , Donepezila/uso terapêutico , Ratos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Demência/tratamento farmacológico , Depressão/tratamento farmacológico , Galantamina/farmacologia , Galantamina/uso terapêutico , Citocinas/metabolismo , Doenças Neuroinflamatórias/tratamento farmacológico , Estresse Psicológico/complicações , Peptídeos beta-Amiloides/metabolismo , Anedonia/efeitos dos fármacosRESUMO
Obesity causes inflammation in the adipose tissue and can affect the central nervous system, leading to oxidative stress and mitochondrial dysfunction. Therefore, it becomes necessary to seek new therapeutic alternatives. Gold nanoparticles (GNPs) could take carnitine to the adipose tissue, thus increasing fatty acid oxidation, reducing inflammation, and, consequently, restoring brain homeostasis. The objective of this study was to investigate the effects of GNPs associated with carnitine on the neurochemical parameters of obesity-induced mice. Eighty male Swiss mice that received a normal lipid diet (control group) or a high-fat diet (obese group) for 10 weeks were used. At the end of the sixth week, the groups were divided for daily treatment with saline, GNPs (70 µg/kg), carnitine (500 mg/kg), or GNPs associated with carnitine, respectively. Body weight was monitored weekly. At the end of the tenth week, the animals were euthanized and the mesenteric fat removed and weighed; the brain structures were separated for biochemical analysis. It was found that obesity caused oxidative damage and mitochondrial dysfunction in brain structures. Treatment with GNPs isolated reduced oxidative stress in the hippocampus. Carnitine isolated decreased the accumulation of mesenteric fat and oxidative stress in the hippocampus. The combination of treatments reduced the accumulation of mesenteric fat and mitochondrial dysfunction in the striatum. Therefore, these treatments in isolation, become a promising option for the treatment of obesity.
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Encéfalo , Carnitina , Modelos Animais de Doenças , Ouro , Nanopartículas Metálicas , Obesidade , Estresse Oxidativo , Animais , Carnitina/farmacologia , Carnitina/administração & dosagem , Carnitina/uso terapêutico , Ouro/farmacologia , Masculino , Obesidade/tratamento farmacológico , Obesidade/patologia , Obesidade/complicações , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Dieta Hiperlipídica , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/patologia , Lesões Encefálicas/metabolismo , Peso Corporal/efeitos dos fármacosRESUMO
Chronic hyperglycemia caused by diabetes mellitus (DM) slows down the healing process due to prolonged inflammation which impedes the regeneration progression. Photobiomodulation (PBM) is considered a non-pharmacological intervention and has anti-inflammatory and biostimulatory effects that accelerate the healing process. Currently found IL-1ß inhibitors are difficult to implement due to their cytotoxic potential, excessive amounts, and invasive administration, and therefore, the application of this peptide in diabetic wounds represents a promising intervention to help resolve the inflammatory response. This study aimed to investigate the effect of an IL-1ß inhibitor molecule associated with PBM irradiation in a model of epithelial injury in diabetic mice. After the induction of the DM model with streptozotocin (STZ), the skin lesion model was implemented through surgical excision. Sixty C57BL/6 mice divided into five experimental groups (n = 12) were used: excisional wound (EW), DM + EW, DM + EW + DAP 1-2 (inhibitor peptide), DM + EW + PBM, and DM + EW + PBM + DAP 1-2. Treatment started 12 h after wound induction and was performed daily for 5 days. Twenty-four hours after the last application, the animals were euthanized and the outer edge of the wound was removed. The results obtained demonstrate that the DM + EW + PBM + DAP 1-2 group caused a reduction in the levels of pro-inflammatory cytokines, an increase in anti-inflammatory cytokines, and an increase in TGF-ß and maintenance of the cellular redox state with a consequent reduction in levels of inflammatory infiltrate and concomitant stimulation of type III collagen gene expression, as well as a decrease in the size of the wound in square centimeter 6 days after the injury. Only the combination of therapies was able to favor the process of tissue regeneration due to the development of an approach capable of acting at different stages of the regenerative process, through the mechanisms of action of interventions on the inflammatory process by avoiding its stagnation and stimulating progression of regeneration.