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Background and Objectives: The hormonal state of hypoestrogenism is associated with the accumulation of white adipose tissue, which can induce an increase in pro-inflammatory markers, leading to progressive health complications. Melatonin can act on adipose tissue mass, promoting its reduction and influencing inflammation, reducing IL-6 and releasing IL-10, pro- and anti-inflammatory markers, respectively. However, the role of melatonin regarding such parameters under the context of hypoestrogenism remains unknown. The aim of this study was to determine the effect of 12 weeks of hypoestrogenism and melatonin on white adipose tissue mass and circulating levels of IL-6, IL-10, TGF-β-1, and leukotriene C4 (LTC4). Materials and Methods: The animals (Wistar rats with sixteen weeks of age at the beginning of the experiment) under hypoestrogenism were submitted to the surgical technique of bilateral ovariectomy. The animals received melatonin (10 mg·kg−1) or vehicles by orogastric gavage every day for 12 weeks and administration occurred systematically 1 h after the beginning of the dark period. White adipose tissue (perigonadal, peritoneal, and subcutaneous) was collected for mass recording, while blood was collected for the serum determination of IL-6, IL-10, TGF-β-1, and LTC4. Results: Hypoestrogenism increased the perigonadal and subcutaneous mass and IL-6 levels. Melatonin kept hypoestrogenic animals in physiological conditions similar to the control group and increased thymus tissue mass. Conclusions: Hypoestrogenism appears to have a negative impact on white adipose tissue mass and IL-6 and although melatonin commonly exerts a significant effect in preventing these changes, this study did not have a sufficiently negative impact caused by hypoestrogenism for melatonin to promote certain benefits. [ABSTRACT FROM AUTHOR]

Background/Aims: Swine erysipelas is a disease caused by Erysipelothrix rhusiopathiae, a Gram-positive bacillus, which has great economic importance because it leads to the loss of the swine herd. To control this disease, animals are immunized with a cellular vaccine of killed or attenuated E. rhusiopathiae, but even with herd vaccination, cases of swine erysipelas outbreaks have been reported in the United States, China and Japan, leading to the search for other antigenic components of the bacteria that may promote greater protection against E. rhusiopathiae. The surface protein SpaA from E. rhusiopathiae has been shown to be a candidate to constitute a subunit vaccine, since it has already been reported to induce a host immune response against the bacterium. DnaK, a hsp70 molecular chaperone, also seems to be a good candidate in the composition of a vaccine, as it has been demonstrated to be an antigenic protein of the bacteria. Methods: This work evaluated the immunogenicity and protection induced by the E. rhusiopathiae SpaA and DnaK recombinant proteins in a murine model, by intramuscular administration to mice with two doses of 100 µg at 21-day interval between them. The candidate proteins were tested either separately and together, compared with the commercial vaccine and the non-vaccination condition, and mice were challenged with a virulent strain of E. rhusiopathiae. Serum was collected to assess the produced antibodies and peripheral blood cells, whereas spleen and kidney tissues were assayed for E. rhusiopathiae [ABSTRACT FROM AUTHOR]

Background/Aims: A new type of nanoparticle, called NP CB-EDA (Black Carbon modified with ethylenediamine), is commonly used in the oil industry. In the literature, few studies are found in biological models, making NP-EDA potential cytotoxicity in organisms unclear. As its large surface area is capable of interacting with the biological system, that interaction could lead to factors harmful to health. The objective of this study was to investigate the cytotoxic effect of NP CB-EDA on fibroblasts LA-9 at 24 and 48 hours, at different concentrations of the nanoparticle (1, 50, 250, 500 and 1000 µg/ml). Methods: NP CB-EDA was characterized by TEM microscopy and its effect on cell viability (MTT method), cell morphology (optical microscopy), cell membrane (lactate dehydrogenase release - LDH), oxidative stress pathways (species levels reactive oxygen, ROS and nitrogen, NOS) and apoptosis/necrosis (flow cytometry) were evaluated. Results: The results show that NP CB-EDA at concentrations of 500 and 1000 µg/ ml form clusters. The nanoparticle can be absorbed by cells decreasing cell viability. There was damage to the cell membrane of fibroblasts LA 9, an increase in the production of ROS, NOS and pro-inflammatory interleukins TNF-α and IL-6; it was also observed an increase in % of cells in the state of apoptosis in the two periods analyzed, being this response more significant in 24 hours, and concentrations of 250, 500 and 1000 µg/ml presenting higher cytotoxicity. Conclusion: The data suggest that NP CB-EDA in fibroblasts LA9 presents cytotoxic potential, which is associated with oxidative stress and apoptosis. [ABSTRACT FROM AUTHOR]

Unlabelled: The significance of polyphenol intake for the prevention of chronic diseases is controversial.Objective: this study investigated the chemical composition and antioxidant potential of an anthocyanin-rich extract from Euterpe edulis fruits (LPEF) and its effects on liver steatosis in dyslipidemic apoE-/- knockout mice.Materials and Methods: mice were divided into G1 (C57BL/6) standard diet; G2 (apoE-/-) standard diet, G3 (apoE-/-) 2% LPEF, G4 (apoE-/-) 6% LPEF, G5 (apoE-/-) 10% LPEF, G6 (apoE-/-) 2% α-tocopherol acetate. After 75 days of treatment, the animals were euthanized. The LPEF contained a high level of monomeric anthocyanins (301.4 mg/100g) and marked antioxidant activity.Results: Catalase activity was reduced in G3, G4, G5 and G6 compared to G2. Superoxide dismutase was reduced only in G4. The animals in G4, G5, and G6 showed low HDL and triglycerides levels compared to G2. The proportion of lipid droplets in liver tissue was reduced in G4 and G5 compared to G2, G3, and G6.Conclusion: The results indicated that E. edulis pulp is rich in anthocyanins and the LPEF dietary consumption can reduce the severity of liver steatosis in apoE-/- mice, an effect that is potentially mediated by the antioxidant activity of this extract and modulation of triglyceride serum levels. [ABSTRACT FROM AUTHOR]

Background: While type 1 diabetes mellitus (T1DM) increases bone fragility physical exercise improves bone quality and strength. Research question: To test whether swimming training attenuates the deterioration of femoral neck structural and mechanical properties in growing rats with untreated streptozotocin (STZ)-induced T1DM. Type of study: Randomised controlled study. Methods: Male Wistar rats (4-weeks-old; initial body weight: 80-90 g) were divided into 4 groups of 10 animals: diabetes sedentary (DS; 60 mg/kg of STZ, single i.p.); diabetes exercised (DE; 60 mg/kg of STZ, single i.p.); control sedentary (CS, same single dose of vehicle); and control exercised (CE, same single dose of vehicle). Six weeks later animals from DE and CE groups underwent a low-intensity swimming training (5 sessions/wk, 90 min/session, load: 4% of body weight) for 8 weeks. The femoral neck mechanical properties were measured. Bone mineral density (BMD) and mineral content (BMC), as well as the femoral neck bone volume (BV/TV) and collagen content were assessed. Results: Rats with T1DM exhibited reduced body weight, femoral weight and length, BMC and BMD, femoral neck collagen content, BV/TV, trabecular thickness, maximum load, stiffness and tenacity, and increased trabecular spacing compared to controls. Swimming training increased femoral BMC and BMD, femoral neck collagen content, BV/TV, trabecular thickness, stiffness and yield point energy, and reduced trabecular spacing in control animals, but not in T1DM animals. Conclusion: Low-intensity swimming training seems to be ineffective in attenuating the deterioration of the femoral neck structural and mechanical properties in growing rats with untreated STZ-induced T1DM. [ABSTRACT FROM AUTHOR]

This study aimed to determine the concentrations of inflammatory markers in visceral adipose tissue (VAT) and skeletal muscle, and changes in body mass and adipocyte size in diet-induced obese rats after moderate-intensity continuous training (MICT) and/or dietary intervention. After 8 weeks of obesity induction through a high-fat diet (HFD) consumption, twenty diet-induced obese male Wistar rats were divided into four groups as follows: (i) control rats fed with HFD (HFD-SED), (ii) obese rats fed with HFD and submitted to MICT (HFD-MICT), (iii) obese rats that were submitted to a nutritional intervention by switching HFD to chow diet (CD-SED), and (iv) obese rats that were submitted to MICT and nutritional intervention (CD-MICT). All the animals in the training groups were submitted to MICT, with an intensity of 50-85% of V max , 60 min/day, 3 days/week for 8 weeks. Gastrocnemius muscle (GAST) and mesenteric adipose tissue (mWAT) were collected to quantify tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, and IL-10 using ELISA. The body mass was recorded before and after the experimental protocols, and the adipocyte morphology was assessed using histological analysis. The results showed that HFD-SED had higher body mass, higher concentrations of inflammatory markers in mWAT, and higher increase in adipocyte size. The CD-SED and CD-MICT groups presented with reduced body mass, relative weight of mWAT, and adipocyte size. Moreover, the inflammatory markers in mWAT were reduced after dietary intervention (TNF-α), MICT (IL-10 and TNF-α), or both interventions combined (IL-6 and TNF-α). In contrast, there was no reduction in GAST-relative weight or concentrations of inflammatory markers for any treatment. Finally, we concluded that 8 weeks of dietary intervention alone and combined with MICT were effective in reducing some of the deleterious effects caused by obesity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Costa, Furino, Castro, Alves and Duarte.)

Obesity is an epidemic disease and the expansion of adipose tissue, especially visceral fat, promotes the secretion of factors that lead to comorbidities such as diabetes and cardiovascular diseases. Thus, diet and exercise have been proposed as an intervention to reverse these complications. An adipocytokine, known as irisin, mediates the beneficial effects of exercise. It has been proposed as a therapeutic potential in controlling obesity. In view of the above, this paper attempts to determine the modulation of irisin, visceral adiposity and biochemical markers in response to dietary intervention and aerobic exercise. To do this, 52 diet-induced obese male Wistar rats were divided into the following four groups: high-fat diet and exercise (HFD-Ex); HFD-Sedentary (HFD-Sed); chow-diet and exercise (CD-Exercise); and CD-Sed. The exercise-trained group performed a treadmill protocol for 60 min/day, 3 days/week for 8 weeks. Body mass (BM), body fat (BF), fat mass (FM), and fat-free mass (FFM) were analyzed. Mesenteric (MES), epididymal (EPI), and retroperitoneal (RET) adipose tissue was collected and histological analysis was performed. Biochemical irisin, triglycerides, glucose, insulin and inflammatory markers were determined and, FNDC5 protein expression was analyzed. In this study, the diet was the most important factor in reducing visceral adiposity in the short and long term. Exercise was an important factor in preserving muscle mass and reducing visceral depots after a long term. Moreover, the combination of diet and exercise can enhance these effects. Diet and exercise exclusively were the factors capable of increasing the values of irisin/FNDC5, however it did not bring cumulative effects of both interventions. Prescriptions to enhance the obesity treatments should involve reducing visceral adiposity by reducing the fat content in the diet associated with aerobic exercise., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Furino, Alves, Marine, Sene-Fiorese, Rodrigues, Arrais-Lima, Mattiello, Castro, Borra, Rocha, Malavazi and Duarte.)

Background/aims: Cancer is the second most deadly disease in the world. The bladder cancer is one of the most aggressive types and shows a continuous increase in the number of cases. The use of bacteria as live vectors to deliver molecules directly to the tumor is a promising tool and has been used as an adjuvant treatment against several types of cancer. The aim of this study was to investigate the antitumor effect of Interleukin 2 (IL-2), TNF-related apoptosis-inducing ligand (TRAIL) and protein MIX against murine bladder cancer cells, lineage MB49., Methods: The attenuated Salmonella strain SL3261 was transformed by inserting the IL-2 and TRAIL genes. The effects of proteins on cell viability (MTT method), cell morphology (optical microscopy), cell recovery (clonogenic assay), cell membrane (lactate dehydrogenase release - LDH), on oxidative stress pathway (levels of nitric oxide, NO) and apoptosis (flow cytometry and high resolution epifluorescence images) were evaluated at intervals of 24 and 48 hours of action., Results: The results showed that there was a decrease in cell viability via damage to the cell membrane, alteration of cell morphology, non-recovery of cells, increase in the production of NO and incubate for of cells in the state of apoptosis in the two periods analyzed., Conclusion: The data presented suggest that IL-2, TRAIL and their MIX proteins in MB49 cells have cytotoxic potential and that this is associated with oxidative stress and apoptosis pathways. These results may contribute to the development of new therapeutic strategies for bladder cancer., Competing Interests: The authors have no conflicts of interest to declare., (© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)

This study aimed to determine the expression of omentin and vaspin, inflammatory markers, body composition, and lipid profile in diet-induced obese rats and high-intensity interval training (HIIT). Forty Wistar rats were divided into four groups: untrained normal diet, trained normal diet (T-ND), untrained high-fat diet (Unt-HFD), and trained high-fat diet (T-HFD). For the animals of the Unt-HFD and T-HFD groups, a high-fat diet was offered for 4 weeks. After that, all the animals in the T-ND and T-HFD groups were submitted to HITT, three times per week, for 10 weeks (2 weeks of adaptation and 8 weeks of HIIT). Muscle (gastrocnemius), liver, epididymal adipose tissue, retroperitoneal adipose tissue, visceral adipose tissue (VAT), and serum were collected to analyze TNF-α, IL-6, PCR, IL-8, IL-10, IL-4, vaspin, and omentin. A body composition analysis was performed before adaptation to HIIT protocol and after the last exercise session using dual-energy X-ray absorptiometry. Omentin and vaspin in the VAT were quantified using Western blotting. The results showed that, when fed a high-fat diet, the animals obtained significant gains in body fat and elevated serum concentrations of vaspin and blood triglycerides. The HIIT was able to minimize body fat gain but did not reduce visceral fat despite the increase in maximum exercise capacity. Moreover, there was a reduction in the serum levels of adiponectin, IL-6, and IL-10. Finally, we concluded that, although the training protocol was able to slow down the weight gain of the animals, there was no reduction in visceral fat or an improvement in the inflammatory profile, including no changes in omentin and vaspin., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Costa, Castro, Marine, Fabrizzi, Furino, Malavazi, Anibal and Duarte.)

Schistosomiasis, caused by Schistosoma mansoni trematode worm, affects more than 1.5 million people in Brazil. The current treatment consists in the administration of Praziquantel, the only medicine used for treatment for more than 40 years. Some of the limitations of this drug consist in its inactivity against schistosomula and parasite eggs, the appearance of resistant strains and non-prevention against reinfection. Thus, the objective of this study was to evaluate the effect of immunization with recombinant functional enzymes of the purine salvage pathway of S. mansoni , Nucleoside Diphosphate Kinase (NDPK) and Adenylosuccinate Lyase (ADSL), to evaluate the host immune response, as well as the parasite load after vaccination. For this, Balb/c mice were divided into 5 groups: control (uninfected and untreated), non-immunized/infected, NDPK infected, ADSL infected, and NDPK + ADSL infected. Immunized groups received three enzyme dosages, with a 15-day interval between each dose, and after 15 days of the last application the animals were infected with 80 cercariae of S. mansoni . On the 47th day after the infection, fecal eggs were counted and, on the 48th day after the infection, the evaluation of leukocyte response, parasite load, antibody production, cytokines quantification, and histopathological analysis were performed. The results showed that immunizations with NDPK, ADSL or NDPK + ADSL promoted a discreet reduction in eosinophil counts in lavage of peritoneal cavity. All immunized animals showed increased production and secretion of IgG1, IgG2a, and IgE antibodies. Increased production of IL-4 was observed in the group immunized with the combination of both enzymes (NDPK + ADSL). In addition, in all immunized groups there were reductions in egg counts in the liver and intestine, such as reductions in liver granulomas. Thus, we suggest that immunizations with these enzymes could contribute to the reduction of schistosomiasis transmission, besides being important in immunopathogenesis control of the disease., (Copyright © 2020 Cagnazzo, Nogueira, Castro, Neris, Fattori, Correia, Albuquerque, Fragelli, Mendes, Allegretti, Soares, Romanello, Torini, Pereira and Anibal.)

Leishmaniases are diseases with high epidemiological relevance and wide geographical distribution. In Brazil, Leishmania (Leishmania) amazonensis is related to the tegumentary form of leishmaniasis. The treatment for those diseases is problematic as the available drugs promote adverse effects in patients. Therefore, it is important to find new therapeutic targets. In this regard, one alternative is the study of biomolecules produced by endophytic microorganisms. In this study, the total extract produced by the endophytic Paenibacillus polymyxa RNC-D was used to evaluate the leishmanicidal, nitric oxide, and cytokines production using RAW 264.7 macrophages. The results showed that, in the leishmanicidal assay with L. amazonensis , EC50 values at the periods of 24 and 48 hours were 0.624 mg/mL and 0.547 mg/mL, respectively. Furthermore, the cells treated with the extract presented approximately 25% of infected cells with an average of 3 amastigotes/cell in the periods of 24 and 48 hours. Regarding the production of cytokines in RAW 264.7 macrophages infected/treated with the extract, a significant increase in TNF- α was observed at the periods of 24 and 48 hours in the treated cells. The concentrations of IFN- γ and IL-12 showed significant increase in 48 hours. A significant decrease in IL-4 was observed in all cells treated with the extract in 24 hours. It was observed in the treated cells that the NO production by RAW 264.7 macrophages increased between 48 and 72 hours. The endophytic Paenibacillus polymyxa RNC-D extract modulates the mediators of inflammation produced by RAW 264.7 macrophages promoting L. amazonensis death. The immunomodulatory effects might be a promising target to develop new immunotherapeutic and antileishmanial drugs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (Copyright © 2020 Débora Meira Neris et al.)

This study aims to analyze the effects of resisted, aerobic, and combined exercises on omentin levels in visceral adipose tissue and muscle of rats with experimental diabetes to verify whether these adipokines are related to the glucose pathway and inflammation process in this model. Male Wistar rats received a high-fat diet for 4 weeks and a low dose of streptozotocin (35 mg/kg) to induce experimental diabetes. After inducing diabetes, the animals were divided into 4 experimental groups ( n = 10): diabetic control (C); resistance training (RT); aerobic training (AT); and combined training (CT). The groups were exercised for 12 weeks, 3 times/week, where: RT means the stair climbing protocol until exhaustion; AT is the 30 min/day reaching 20 m/min protocol, and CT is the combination of RT and AT. The AT group showed reduced retroperitoneal and mesenteric adipose tissue and abdominal fat deposits. Our study also showed a possible control of blood glucose, as well as decreased Interleukin 6 (IL-6) and C-reactive protein, increased circulating adiponectin and increased omentin in visceral adipose tissue. In addition, the AT group affected the glucose pathway by stimulating phosphorylation of Akt in muscle tissue. Omentin also showed a strong positive correlation with adiponectin and a moderate negative correlation with IL-6. Thus, our findings indicated that omentin in type 2 diabetes is changed by AT. Furthermore, increased omentin levels had a close association with the glucose pathway by stimulating phosphorylation of Akt in muscle tissue and with IL-6 in serum, suggesting that omentin is likely to have anti-inflammatory and protective action in experimental diabetes.