Electrospun skin dressings for diabetic wound treatment: a systematic review.

Abstract: Diabetes mellitus is a metabolic disease characterized by persistent hyperglycemia associated with a lack of insulin production or insulin resistance. In diabetic patients, the capacity for healing is generally decreased, leading to chronic wounds. One of the most common treatments for chronic wounds is skin dressings, which serve as protection from infection, reduce pain levels, and stimulate tissue healing. Furthermore, electrospinning is one of the most effective techniques used for manufacturing skin dressings. Objective: The purpose of this study was to perform a systematic review of the literature to examine the effects of electrospun skin dressings from different sources in the process of healing skin wounds using in vivo experiments in diabetic rats. Methods: The search was carried out according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and the Medical Subject Headings (MeSH) descriptors were defined as "wound dressing," "diabetes," "in vivo," and "electrospun." A total of 14 articles were retrieved from PubMed and Scopus databases. Results: The results were based mainly on histological analysis and macroscopic evaluation, demonstrating moderate evidence synthesis for all experimental studies, showing a positive effect of electrospun skin dressings for diabetic wound treatment. Conclusion: This review confirms the significant benefits of using electrospun skin dressings for skin repair and regeneration. All the inks used were demonstrated to be suitable for dressing manufacturing. Moreover, in vivo findings showed full wound closure in most of the studies, with well-organized dermal and epidermal layers.

Supplementation of carotenoids from peach palm waste (Bactris gasipaes) obtained with an ionic liquid mediated process displays kidney anti-inflammatory and antioxidant outcomes.

Sustainable extraction processes based on alternative solvents to recover bioactive compounds of different raw materials have been highlighted as excellent alternatives to supply the needs of society towards a bioeconomy strategy. Little is known about the safety and biological effect of compounds extracted by these processes. In this work, carotenoids from Bactris gasipaes wastes obtained by an IL-based process were investigated in terms of safety, anti-inflammatory and, antioxidant activity in a high-fat-diet animal model on the kidney. Wistar rats were supplemented or not by carotenoids extracted with IL or VOS. The animals supplemented with carotenoids had lower weight than control and high-fat diets. In the animals supplemented with carotenoids, the group IL improved anti-inflammatory and antioxidant activity compared with carotenoids obtained by VOS. Also, the group HFD-VOS showed moderate-severe injuries on the kidney. Then, ILs could represent a novel tool for natural pigments safely applied to food industry.

Dehydrodieugenol improved lung inflammation in an asthma model by inhibiting the STAT3/SOCS3 and MAPK pathways.

BACKGROUND: Eugenol, a common phenylpropanoid derivative found in different plant species, has well-described anti-inflammatory effects associated with the development of occupational hypersensitive asthma. Dehydrodieugenol, a dimeric eugenol derivative, exhibits anti-inflammatory and antioxidant activities and can be found in the Brazilian plant species Nectandra leucantha (Lauraceae). The biological effects of dehydrodieugenol on lung inflammation remain unclear. PURPOSE: This study aimed to investigate the effects of eugenol and dehydrodieugenol isolated from N. leucantha in an experimental model of asthma. METHODS: In the present work, the toxic effects of eugenol and dehydrodieugenol on RAW 264.7 cells and their oxidant and inflammatory effects before lipopolysaccharide (LPS) exposure were tested. Then, male BALB/c mice were sensitized with ovalbumin through a 29-day protocol and treated with vehicle, eugenol, dehydrodieugenol or dexamethasone for eight days beginning on the 22nd day until the end of the protocol. Lung function; the inflammatory profile; and the protein expression of ERK1/2, JNK, p38, VAChT, STAT3, and SOCS3 in the lung were evaluated by immunoblotting. RESULTS: Eugenol and dehydrodieugenol were nontoxic to cells. Both compounds inhibited NO release and the gene expression of IL-1ß and IL-6 in LPS-stimulated RAW 264.7 cells. In OVA-sensitized animals, dehydrodieugenol reduced lung inflammatory cell numbers and the lung concentrations of IL-4, IL-13, IL-17, and IL-10. These anti-inflammatory effects were associated with inhibition of the JNK, p38 and ERK1/2, VAChT and STAT3/SOCS3 pathways. Moreover, treatment with dehydrodieugenol effectively attenuated airway hyperresponsiveness. CONCLUSION: The obtained data demonstrate, for the first time, that dehydrodieugenol was more effective than eugenol in counteracting allergic airway inflammation in mice, especially its inhibition of the JNK, p38 and ERK1/2, components of MAPK pathway. Therefore, dehydrodieugenol can be considered a prototype for the development of new and effective agents for the treatment of asthmatic patients.

Gum arabic reduces inflammation, oxidative, and nitrosative stress in the gastrointestinal tract of mice with chronic kidney disease.

The aim of this study was to investigate some biochemical indices of inflammation and oxidative and nitrosative stresses in the gastrointestinal tract of mice with experimental chronic kidney disease (CKD) and treated with gum arabic (GA). Male CD1 mice (n = 28) were randomly distributed into four groups and treated for four consecutive weeks: group 1: Control: received the same diet without treatment until the end of the study; group 2: Adenine: switched to a powder diet containing adenine (0.2% w/w in feed); group 3: Gum acacia (GA): given normal feed and GA in drinking water at a concentration of 15% w/v; and group 4: Adenine + GA: given adenine in the feed as in the second group plus GA in the drinking water at concentration of 15% w/v. CKD was induced to mice by adenine feeding and concomitantly treated with the prebiotic dietary fiber gum acacia, GA (15% in drinking water). Duodenal mucosa from CKD mice had significantly higher concentrations of TNF-alfa, IL- 6, and TGF-beta-1 and lipid peroxidation. Moreover, low concentrations of IL-10, some antioxidants (catalase, glutathione reductase, total antioxidant capacity, and superoxide dismutase), and nuclear factor erythroid 2-related factor 2 were found in the duodenum. The levels of nitrosative stress (nitrite, nitrate, and total nitrate) were significantly increased by CKD, as well as the concentrations of ammonia and urea creatinine in the cecal content. Concomitant GA treatment significantly mitigated these harmful effects. Taken together, GA reduces inflammation and duodenal oxidative and nitrosative stress in the gastrointestinal tract of mice with CKD.

Low concentrations of sodium arsenite induce hepatotoxicity in prepubertal male rats.

Arsenic (As) can contaminate air, soil, water, and organisms through mobilization of natural mineralogical deposits or anthropogenic actions. Inorganic-As compounds are more toxic and widely available in aquatic environments, including drinking water reservoir catchments. Since little is known about its effects on prepubertal mammals, the present study focused on it. Hence, As was administered through drinking water to male Wistar rats from postnatal day 23 to 53. Negative control group received vehicle only (filtered water); As 1 group received AsNaO2 at 0.01 mg L-1 and As2 group received AsNaO2 at 10 mg L-1 . It was investigated hepatic and renal toxicity of AsNaO2 (ie, histopathology and apoptosis analysis), as well as its mutagenicity (ie, micronucleus test in liver and bone marrow), cytotoxicity (ie, frequency and type of erythrocytes in blood), and genotoxicity (ie, comet assay in blood). Also, As determination was performed in hepatic and renal tissues. Data obtained revealed that immature organisms present a pattern of arsenic accumulation similar to that observed in adults, suggesting similarity in metabolic processes. In addition, liver showed to be an important target tissue for As toxicity in these experimental conditions, exhibiting infiltrate of defense cells, DNA damages, and increased apoptosis rates.

Inhibition of MAPK and STAT3-SOCS3 by Sakuranetin Attenuated Chronic Allergic Airway Inflammation in Mice.

Asthma allergic disease is caused by airway chronic inflammation. Some intracellular signaling pathways, such as MAPK and STAT3-SOCS3, are involved in the control of airway inflammation in asthma. The flavonoid sakuranetin demonstrated an anti-inflammatory effect in different asthma models. Our aim was to clarify how sakuranetin treatment affects MAPK and STAT3-SOCS3 pathways in a murine experimental asthma model. Mice were submitted to an asthma ovalbumin-induction protocol and were treated with vehicle, sakuranetin, or dexamethasone. We assayed the inflammatory profile, mucus production, and serum antibody, STAT3-SOCS3, and MAPK levels in the lungs. Morphological alterations were also evaluated in the liver. LPS-stimulated RAW 264.7 cells were used to evaluate the effects of sakuranetin on nitric oxide (NO) and cytokine production. In vivo, sakuranetin treatment reduced serum IgE levels, lung inflammation (eosinophils, neutrophils, and Th2/Th17 cytokines), and respiratory epithelial mucus production in ovalbumin-sensitized animals. Considering possible mechanisms, sakuranetin inhibits the activation of ERK1/2, JNK, p38, and STAT3 in the lungs. No alterations were found in the liver for treated animals. Sakuranetin did not modify in vitro cell viability in RAW 264.7 and reduced NO release and gene expression of IL-1ß and IL-6 induced by LPS in these cells. In conclusion, our data showed that the inhibitory effects of sakuranetin on eosinophilic lung inflammation can be due to the inhibition of Th2 and Th17 cytokines and the inhibition of MAPK and STAT3 pathways, reinforcing the idea that sakuranetin can be considered a relevant candidate for the treatment of inflammatory allergic airway disease.

Role of polyphenols and nonpolyphenols against toxicity induced by fluoride: a comprehensive review.

Since its discovery as an antimicrobial agent, fluoride has been used in the control of dental caries. Many studies have shown that the chronic exposure of fluoride in high concentrations causes adverse effects in multiple organs; the use of bioactive compounds present in foods as a tool to mitigate the effects of fluoride could potentially be useful for populations in different parts of the world are exposed to fluoride in a chronic and systemic way. Thus, the aim of this comprehensive review is to present and discuss the published papers that focused on the use of polyphenols and nonpolyphenols that can mitigate the harmful activities promoted by fluoride exposure. Certainly, these data will contribute toward a better understanding of the role of food compounds in the pathological outcomes induced by fluoride. The new information will be added to that already available for regulatory purposes as a safe way to promote oral healthcare and prevent oral carcinogenesis.

Sleep deprivation induces pathological changes in rat masticatory muscles: Role of Toll like signaling pathway and atrophy.

The aim of this study was to evaluate the Toll like signaling pathway and atrophy after sleep deprivation (SD) in rat masticatory muscles: masseter and temporal. A total of 24 animals was distributed into three groups: Control group (CTL, n = 8), subjected to SD for 96 h (SD96, n = 8) and subjected to SD for 96 h more 96 h of sleep recovery (SD96 + R, n = 8). Histopathological analysis revealed the presence of acute inflammatory cells, congested vessels, fibrosis, and high cellularity in the skeletal muscle fibers from masseter and temporal submitted to SD. These morphological alterations were not observed in the control group since neither inflammatory cells nor congested vessels were observed to this group. In the group SD96 + R, the absence of inflammation was noticed to the masseter only. In this group, COX-2 and TNF-alpha downregulation were detected when comparing to control group. MyD88 and pIKK decreased in SD96 and SD96 + R groups being pNFKBp50 downregulatated in SD96 + R. MyD88 expression increased in rats submitted to SD96 and SD96 + R in temporal when compared to control group. On the other hand, pIKK decreased the protein expression in groups SD96 and SD96 + R while pNFKBp50 showed a decreased protein expression in group SD96 only. The activation of atrophy by means of MAFbx upregulation was detected in temporal muscle in SD96 and SD96 + R when compared to control. In summary, our results show that SD is able to induce morphological alterations in rat masticatory muscles. Toll like signaling pathway and atrophy play important roles in ethiopathogenesis induced by SD, being dependent of skeletal muscle type.

Grape skin extract mitigates tissue degeneration, genotoxicity, and oxidative status in multiple organs of rats exposed to cadmium.

The aim of this study was to investigate whether grape skin extract can mitigate the noxious activities induced by cadmium exposure in multiple organs of rats. For this purpose, histopathological analysis for the liver, genotoxicity, and oxidative status in the blood and liver were investigated in this setting. A total of 20 Wistar rats weighing 250 g, on average, and 8 weeks of age were distributed into four groups (n=5) as follows: control group (nontreated group); cadmium group (Cd); and grape skin extract groups (Cd+GS) at 175 or 350 mg/l. Histopathological analysis in liver showed that animals treated with grape skin extract showed improved tissue degeneration induced by cadmium intoxication. Genetic damage was reduced in blood and hepatocytes as indicated by comet and micronucleus assays in animals treated with grape skin extract. Copper-zinc superoxide dismutase and cytochrome c gene expression increased in groups treated with grape skin extract in liver cells. Grape skin extract also reduced the 8-hydroxy-2'-deoxyguanosine levels in liver cells compared with the cadmium group. Taken together, our results indicate that grape skin extract can mitigate tissue degeneration, genotoxicity, and oxidative stress induced by cadmium exposure in multiple organs of Wistar rats.

Prebiotic and Synbiotic Modifications of Beta Oxidation and Lipogenic Gene Expression after Experimental Hypercholesterolemia in Rat Liver.

Background and aims: Non-alcoholic fatty liver disease (NAFLD) is characterized by the presence of fat in hepatocytes because of decreased ß-oxidation and increased lipogenesis. Prebiotics, probiotics, and synbiotic have modulatory effects on intestinal microbiota and may influence the gut-liver axis. Our aim was to evaluate the effects of prebiotic, probiotics, and synbiotic on liver histopathology and gene expression related to ß-oxidation and lipogenesis after hypercholesterolemia. Methods: Wistar male adult rats (n = 40) were submitted to hypercholesterolemic conditions (HPC) (60 days). On Day 30 of HPC, rats were subdivided in 5 groups: negative control (NC): without HPC + Gv (distilled water); positive control (PC): with HPC + Gv (distilled water); prebiotic (PRE): HPC + Gv with prebiotic (Fiber FOS®); probiotic (PRO): HPC + Gv with probiotic strains Gv (Probiatop®); and synbiotic (SYN): HPC + Gv with synbiotic (Simbioflora®). All rats were sacrificed on Day 30 post-treatment. Blood was collected to verify total serum cholesterol, and liver tissue was sampled to verify histopathological changes and gene expression. Gene expression related to ß-oxidation (PPAR-α and CPT-1) and lipogenesis (SREBP-1c, FAS and ME) was evaluated in liver tissue using RT-qPCR. Results: PC had higher cholesterol levels when compared to NC. PRE and SYN rats had lower cholesterol levels than PC. PC rats showed more histopathological changes than NC rats; PRE and SYN rats showed fewer alterations than PC rats. PPAR-α was expressed at higher levels in SYN and PC rats compared with PRE and PRO rats. CPT-1 expression was similar in all groups. SREBP-1c was expressed at higher levels in PC rats compared with NC rats; levels were lower in SYN rats compared with PRO rats; levels were lower in PRE rats compared with PC and PRO rats. FAS was expressed at lower levels in PRE rats compared with SYN rats. ME expression was lower in PC rats compared with NC rats. Conclusion: Prebiotic and synbiotic supplementation improve hepatic alterations related to hypercholesterolemia. These changes appear to be mediated by altered expression of genes related to ß-oxidation and lipogenesis.

Influence of Oral and Gut Microbiota in the Health of Menopausal Women.

Sex differences in gut microbiota are acknowledged, and evidence suggests that gut microbiota may have a role in higher incidence and/or severity of autoimmune diseases in females. Additionally, it has been suggested that oral, vaginal, and gut microbiota composition can be regulated by estrogen levels. The association of vaginal microbiota with vulvovaginal atrophy at menopause is well described in the literature. However, the relevance of oral and gut microbiota modulation in the immune system during estrogen deficiency and its effect on inflammatory diseases is not well explored. Estrogen deficiency is a condition that occurs in menopausal women, and it can last approximately 30 years of a woman's life. The purpose of this mini- review is to highlight the importance of alterations in the oral and gut microbiota during estrogen deficiency and their effect on oral and inflammatory diseases that are associated with menopause. Considering that hormone replacement therapy is not always recommended or sufficient to prevent or treat menopause-related disease, we will also discuss the use of probiotics and prebiotics as an option for the prevention or treatment of these diseases.

Intermediate purification of CHO-derived recombinant human Factor IX using hydrophobic interaction membrane-based chromatography and its comparison to a sulfated resin.

This work investigated the use of hydrophobic interaction membrane chromatography for intermediate purification of recombinant human Factor IX (rFIX) produced by CHO cells. The first purification step was based on a strong anion exchange monolith, thus forming a purification process fully based on convective media, which allow operation at high flow rates and low pressure drops, as well as modular scale-up. Although the starting material was challenging (CHO cell culture supernatant harvested at 70% cell viability), the two-step purification process showed promising results, with a global purification factor of 298, a global recovery of 69%, and DNA and endotoxin levels close to regulatory limits. Final host cell DNA (68.8 ng per dose of 500 IU), endotoxins (60 EU per dose of 500 IU) and activated FIX (FIXa/FIX = 2.33%) were in levels close to those recommended by regulatory authorities. HCP removal was of 99.98%, decreasing from 9 424 358 ppm in the supernatant to a final HCP value of 2071 ppm. The use of a supernatant harvested at higher viability and/or the addition of a third polishing step focusing on HCP removal could allow meeting the desired HCP range of 50-100 ppm, as well as the regulatory requirements for the other critical contaminants.