PLA2-MjTX-II from Bothrops moojeni snake venom exhibits antimetastatic and antiangiogenic effects on human lung cancer cells.

Phospholipases A2 (PLA2s) from snake venom possess antitumor and antiangiogenic properties. In this study, we evaluated the antimetastatic and antiangiogenic effects of MjTX-II, a Lys49 PLA2 isolated from Bothrops moojeni venom, on lung cancer and endothelial cells. Using in vitro and ex vivo approaches, we demonstrated that MjTX-II reduced cell proliferation and inhibited fundamental processes for lung cancer cells (A549) growth and metastasis, such as adhesion, migration, invasion, and actin cytoskeleton decrease, without significantly interfering with non-tumorigenic lung cells (BEAS-2B). Furthermore, MjTX-II caused cell cycle alterations, increased reactive oxygen species production, modulated the expression of pro- and antiangiogenic genes, and decreased vascular endothelial growth factor (VEGF) expression in HUVECs. Finally, MjTX-II inhibited ex vivo angiogenesis processes in an aortic ring model. Therefore, we conclude that MjTX-II exhibits antimetastatic and antiangiogenic effects in vitro and ex vivo and represents a molecule that hold promise as a pharmacological model for antitumor therapy.

A novel diselenide attenuates the carrageenan-induced inflammation by reducing neutrophil infiltration and the resulting tissue damage in mice.

Selenium-containing compounds have emerged as promising treatment for redox-based and inflammatory diseases. This study aimed to investigate the in vitro and in vivo anti-inflammatory activity of a novel diselenide named as dibenzyl[diselanediyIbis(propane-3-1diyl)] dicarbamate (DD). DD reacted with HOCl (k = 9.2 x 107 M-1s-1), like glutathione (k = 1.2 x 108 M-1s-1), yielding seleninic and selenonic acid derivatives, and it also decreased HOCl formation by activated human neutrophils (IC50=4.6 µM) and purified myeloperoxidase (MPO) (IC50=3.8 µM). However, tyrosine, MPO-I and MPO-II substrates, did not restore HOCl formation in presence of DD. DD inhibited the oxidative burst in dHL-60 cells with no toxicity up to 25 µM for 48h. Next, an intraperitoneal administration of 25, 50, and 75 mg/kg DD decreased total leukocyte, neutrophil chemotaxis, and inflammation markers (MPO activity, lipid peroxidation, albumin exudation, nitrite, TNF-α, IL-1ß, CXCL1/KC, and CXCL2/MIP-2) on a murine model of carrageenan-induced peritonitis. Likewise, 50 mg/kg DD (i.p.) decreased carrageenan-induced paw edema over 5h. Histological and immunohistochemistry analyses of the paw tissue showed decreased neutrophil count, edema area, and MPO, carbonylated, and nitrated protein staining. Furthermore, DD treatment decreased the fMLP-induced chemotaxis of human neutrophils (IC50=3.7 µM) in vitro with no toxicity. Lastly, DD presented no toxicity in a single-dose model using mice (50 mg/kg, i.p.) over 15 days and in Artemia salina bioassay (50 to 2000 µM), corroborating findings from in silico toxicological study. Altogether, these results demonstrate that DD attenuates carrageenan-induced inflammation mainly by reducing neutrophil migration and the resulting damage from MPO-mediated oxidative burst.

Antiangiogenic properties of BthMP, a P-I metalloproteinase from Bothrops moojeni snake venom by VEGF pathway in endothelial cells.

Angiogenesis is a process that is controlled by a delicate combination of proangiogenic and antiangiogenic molecules and can be disrupted in various illnesses, including cancer. Non-cancerous diseases can also have an abnormal or insufficient vascular growth, inflammation and hypoxia, which exacerbate angiogenesis. These conditions include atherosclerosis, psoriasis, endometriosis, asthma, obesity and AIDS. Based on that, the present work assessed the in vitro and ex vivo antiangiogenic properties stemming from BthMP, a P-I metalloproteinase from Bothrops moojeni snake venom, via the VEGF pathway. BthMP at a concentration of 5 and 40 µg/mL showed no toxicity to endothelial cells (HUVEC) in the MTT assay and was not able to induce necrosis and colony proliferation. Interestingly, BthMP inhibited adhesion, migration and invasion of HUVECs in Matrigel and arrested in vitro angiogenesis by reducing the average number of nodules in toxin-treated cells by 9.6 and 17.32 at 5 and 40 µg/mL, respectively, and the number of tubules by 15.9 at 5 µg/mL and 21.6 at 40 µg/mL in a VEGF-dependent way, an essential proangiogenic property. Furthermore, BthMP inhibited the occurrence of the angiogenic process in an ex vivo aortic ring test by decreasing new vessel formation by 52% at 5 µg/mL and by 66% at 40 µg/mL and by increasing the expression of an antiangiogenic gene, SFLT-1, and decreasing the expression of the proangiogenic genes VEGFA and ANGPT-1. Finally, this toxin reduces the production of nitric oxide, a marker that promotes angiogenesis and VEGF modulation, and decreases the protein expression of VEGFA in the supernatant of the HUVEC culture by about 30 %. These results suggest that BthMP has a promising antiangiogenic property and proves to be a biotechnological mechanism for understanding the antiangiogenic responses induced by snake venom metalloproteinases, which could be applied to a variety of diseases that exhibit an imbalance of angiogenesis mechanisms.

Effects of 5α-dihydrotestosterone on the modulation of monocyte/macrophage response to Staphylococcus aureus: an in vitro study.

BACKGROUND: Staphylococcus aureus (S. aureus) is a pathogen responsible for a wide range of clinical manifestations and potentially fatal conditions. There is a paucity of information on the influence of androgens in the immune response to S. aureus infection. In this study, we evaluated the influence of the hormone 5α-dihydrotestosterone (DHT) on mouse peritoneal macrophages (MPMs) and human peripheral blood monocytes (HPBMs) induced by S. aureus. METHODS: An in vitro model of MPMs from BALB/c sham males, orchiectomised (OQX) males, and females was used. Cells were inoculated with 10 µL of S. aureus, phage-type 80 or sterile saline (control) for 6 h. The MPMs of OQX males and females were pre-treated with 100 µL of 10-2 M DHT for 24 h before inoculation with S. aureus. The concentration of the cytokines TNF-α, IL-1α, IL-6, IL-8, and IL-10; total nitrites (NO-2); and hydrogen peroxide (H2O2) were measured in the supernatant of MPM cultures. In addition, the toll-like receptor 2 (TLR2) and nuclear factor kappa B (NF-kB) genes that are involved in immune responses were analysed. For the in vitro model of HPBMs, nine men and nine women of childbearing age were selected and HPBMs were isolated from samples of the volunteers' peripheral blood. In women, blood was collected during the periovulatory period. The HPBMs were inoculated with S. aureus for 6 h and the supernatant was collected for the analysis of cytokines TNF-α, IL-6, IL-12; and GM-CSF, NO-2, and H2O2. The HPBMs were then removed for the analysis of 84 genes involved in the host's response to bacterial infections by RT-PCR array. GraphPad was used for statistical analysis with a p value < 0.05. RESULTS: Our data demonstrated that MPMs from sham males inoculated with S. aureus displayed higher concentrations of inflammatory cytokines and lower concentrations of IL-10, NO-2, and H2O2 when compared with MPMs from OQX males and females. A similar result was observed in the HPBMs of men when compared with those of women. Previous treatment with DHT in women HPBMs increased the production of pro-inflammatory cytokines and decreased the levels of IL-10, NO-2, and H2O2. The analysis of gene expression showed that DHT increased the activity of the TLR2 and NF-kB pathways in both MPMs and HPBMs. CONCLUSIONS: We found that DHT acts as an inflammatory modulator in the monocyte/macrophage response induced by S. aureus and females exhibit a better immune defence response against this pathogen.

Therapeutic or lifelong training effects on pancreatic morphological and functional parameters in an animal model of aging and obesity.

AIMS: Obesity, aging, and physical training are factors influencing pancreatic functional and morphological parameters. Aiming to clarify the impact of the interaction of these factors, we analyzed the effect of therapeutic or lifelong physical training on body adiposity and pancreatic functional and morphological parameters of aged and obese rats. METHODS: 24 male Wistar rats were (initial age = 4 months and final age = 14 months) randomly divided into three aged and obese experimental groups (n = 8/group): untrained, therapeutic trained, and lifelong trained. Body adiposity, plasmatic concentration and pancreatic immunostaining of insulin, markers of tissue inflammation, lipid peroxidation, activity and immunostaining of antioxidant enzymes, and parameters of pancreatic morphology were evaluated. RESULTS: Lifelong physical training improved the body adiposity, plasmatic insulin concentration, and macrophage immunostaining in the pancreas. The animals submitted to therapeutic and lifelong training showed an increase in the density of the pancreatic islets; lower insulin, Nuclear Factor Kappa B (NF-κB), and Transforming Growth Factor beta (TGF-ß) immunostaining in the pancreatic parenchyma, as well as lower pancreatic tissue lipid peroxidation, lower fibrosis area, increased catalase and glutathione peroxidase (GPx) activity and increased heme oxygenase-1 (HO-1) immunostaining, with the greatest effect in the lifelong training group. CONCLUSION: Lifelong training promoted greater beneficial effects on the pancreatic functional and morphological parameters of aged and obese animals compared to therapeutic exercise.

Time-Course of Redox Status, Redox-Related, and Mitochondrial-Dynamics-Related Gene Expression after an Acute Bout of Different Physical Exercise Protocols.

We investigated the magnitude of exercise-induced changes in muscular bioenergetics, redox balance, mitochondrial function, and gene expression within 24 h after the exercise bouts performed with different intensities, durations, and execution modes (continuous or with intervals). Sixty-five male Swiss mice were divided into four groups: one control (n = 5) and three experimental groups (20 animals/group), submitted to a forced swimming bout with an additional load (% of animal weight): low-intensity continuous (LIC), high-intensity continuous (HIC), and high-intensity interval (HII). Five animals from each group were euthanized at 0 h, 6 h, 12 h, and 24 h postexercise. Gastrocnemius muscle was removed to analyze the expression of genes involved in mitochondrial biogenesis (Ppargc1a), fusion (Mfn2), fission (Dnm1L), and mitophagy (Park2), as well as inflammation (Nos2) and antioxidant defense (Nfe2l2, GPx1). Lipid peroxidation (TBARS), total peroxidase, glutathione peroxidase (GPx), and citrate synthase (CS) activity were also measured. Lactacidemia was measured from a blood sample obtained immediately postexercise. Lactacidemia was higher the higher the exercise intensity (LIC < HIC < HII), while the inverse was observed for TBARS levels. The CS activity was higher in the HII group than the other groups. The antioxidant activity was higher 24 h postexercise in all groups compared to the control and greater in the HII group than the LIC and HIC groups. The gene expression profile exhibited a particular profile for each exercise protocol, but with some similarities between the LIC and HII groups. Taken together, these results suggest that the intervals applied to high-intensity exercise seem to minimize the signs of oxidative damage and drive the mitochondrial dynamics to maintain the mitochondrial network, similar to low-intensity continuous exercise.

Natural vertical cotransmission of Dengue virus and Chikungunya virus from Aedes aegypti in Brumado, Bahia, Brazil.

BACKGROUND: Arthropod-borne viruses have recently emerged and are pathogens of various human diseases, including dengue, zika, and chikungunya viruses. METHODS: We collectedAedes aegyptilarvae (N = 20) from Brumado, Bahia, Brazil, and treated and individually preserved the specimens. We analyzed the samples for dengue, zika, and chikungunya viruses using molecular biology methods. RESULTS: We found that 25% (N = 5) and 15% (N = 3) were positive exclusively for dengue and chikungunya viruses, respectively; 15% (N = 3) were coinfected with both. CONCLUSIONS: This is the first report of dengue and chikungunya virus coinfection in A. aegypti larvae.

Heterologous Expression, Purification, and Immunomodulatory Effects of Recombinant Lipoprotein GUDIV-103 Isolated from Ureaplasma diversum.

Ureaplasma diversum is a bacterial pathogen that infects cattle and can cause severe inflammation of the genital and reproductive systems. Lipid-associated membrane proteins (LAMPs), including GUDIV-103, are the main virulence factors in this bacterium. In this study, we heterologously expressed recombinant GUDIV-103 (rGUDIV-103) in Escherichia coli, purified it, and evaluated its immunological reactivity and immunomodulatory effects in bovine peripheral blood mononuclear cells (PBMCs). Samples from rabbits inoculated with purified rGUDIV-103 were analysed using indirect enzyme-linked immunosorbent assay and dot blotting to confirm polyclonal antibody production and assess kinetics, respectively. The expression of this lipoprotein in field isolates was confirmed via Western blotting with anti-rGUDIV-103 serum and hydrophobic or hydrophilic proteins from 42 U. diversum strains. Moreover, the antibodies produced against the U. diversum ATCC 49783 strain recognised rGUDIV-103. The mitogenic potential of rGUDIV-103 was evaluated using a lymphoproliferation assay in 5(6)-carboxyfluorescein diacetate succinimidyl ester−labelled bovine PBMCs, where it induced lymphocyte proliferation. Quantitative polymerase chain reaction analysis revealed that the expression of interleukin-1ß, toll-like receptor (TLR)-α, TLR2, TLR4, inducible nitric oxide synthase, and caspase-3−encoding genes increased more in rGUDIV-103−treated PBMCs than in untreated cells (p < 0.05). Treating PBMCs with rGUDIV-103 increased nitric oxide and hydrogen peroxide levels. The antigenic and immunogenic properties of rGUDIV-103 suggested its suitability for immunobiological application.

Interaction between cigarette smoke exposure and physical training on inflammatory and oxidative profile in mice muscle.

Regular physical training and cigarette smoke exposure (CSE) have opposite effects on physical performance, antioxidant, and inflammatory profile. However, the interaction between these events is not well studied. We aimed to investigate how regular physical training and CSE interact, and in what is the outcome of this interaction on the physical performance, skeletal muscle antioxidant defense and molecular profile response of pro and anti-inflammatory cytokines. Male C57BL/6 mice were randomly divided into 4 groups (n = 8/group): 1) Sedentary group (SED); 2) 4 weeks of control, followed by 4 weeks of CSE (SED + CSEG); 3) Physically active (PA) along 8 weeks (forced swim training, 5 times a week); 4) Physically active and exposed to the cigarette smoke (PA + CSEG), group submitted to forced swim training for 4 weeks, followed by 4 weeks of concomitant training and CSE. Physical performance was evaluated before and after the experimental period (8 weeks), total peroxidase and glutathione peroxidase (GPx) activities, expression of genes encoding TNF-α, MCP-1, IL1ß, IL-6, IL-10, TGF-ß, HO-1 and the TNF-α/IL-10 ratio were determined from gastrocnemius muscle at the end of experimental period. The CSE attenuated the aerobic capacity adaptation (time to exhaustion in swimming forced test) promoted by physical training and inhibit the improvement in local muscle resistance (inverted screen test). The regular physical training enhanced the antioxidant defense, but the CSE abrogated this benefit. The CSE induced a harmful pro-inflammatory profile in skeletal muscle from sedentary animals whereas the regular physical training induced an opposite adaptation. Likewise, the CSE abolished the protective effect of physical training. Together, these results suggest a negative effect of CSE including, at least in part, the inhibition/attenuation of beneficial adaptations from regular physical training.

Natural vertical cotransmission of Dengue virus and Chikungunya virus from Aedes aegypti in Brumado, Bahia, Brazil

ABSTRACT Background: Arthropod-borne viruses have recently emerged and are pathogens of various human diseases, including dengue, zika, and chikungunya viruses. Methods: We collectedAedes aegyptilarvae (N = 20) from Brumado, Bahia, Brazil, and treated and individually preserved the specimens. We analyzed the samples for dengue, zika, and chikungunya viruses using molecular biology methods. Results: We found that 25% (N = 5) and 15% (N = 3) were positive exclusively for dengue and chikungunya viruses, respectively; 15% (N = 3) were coinfected with both. Conclusions: This is the first report of dengue and chikungunya virus coinfection in A. aegypti larvae.

Relationship between Th17 immune response and cancer.

Cancer is the second leading cause of death worldwide and epidemiological projections predict growing cancer mortality rates in the next decades. Cancer has a close relationship with the immune system and, although Th17 cells are known to play roles in the immune response against microorganisms and in autoimmunity, studies have emphasized their roles in cancer pathogenesis. The Th17 immune response profile is involved in several types of cancer including urogenital, respiratory, gastrointestinal, and skin cancers. This type of immune response exerts pro and antitumor functions through several mechanisms, depending on the context of each tumor, including the protumor angiogenesis and exhaustion of T cells and the antitumor recruitment of T cells and neutrophils to the tumor microenvironment. Among other factors, the paradoxical behavior of Th17 cells in this setting has been attributed to its plasticity potential, which makes possible their conversion into other types of T cells such as Th17/Treg and Th17/Th1 cells. Interleukin (IL)-17 stands out among Th17-related cytokines since it modulates pathways and interacts with other cell profiles in the tumor microenvironment, which allow Th17 cells to prevail in tumors. Moreover, the IL-17 is able to mediate pro and antitumor processes that influence the development and progression of various cancers, being associated with variable clinical outcomes. The understanding of the relationship between the Th17 immune response and cancer as well as the singularities of carcinogenic processes in each type of tumor is crucial for the identification of new therapeutic targets.

Antimicrobial photodynamic therapy (aPDT) with curcumin controls intradermal infection by Staphylococcus aureus in mice with type 1 diabetes mellitus: a pilot study.

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the main pathogens that cause infections in diabetic individuals. In this paper, we report the outcomes of our investigation on the intradermal application of antimicrobial photodynamic therapy (PDT) with curcumin in an infection induced by MRSA ATCC 43300 strain in the ear of mice with Type 1 Diabetes Mellitus (T1DM). A solution containing 100 µg of curcumin was photoactivated ex vivo with a LED light (450 nm) delivering a fluency of 13.5 J/cm3. This solution was administered in the ear intradermally, at the same inoculum site as the MRSA ATCC 43300 strain (PDT Group). This study also included the use of two control groups (both infected): One was treated with saline and the other was treated with non-photoactivated curcumin. The animals were euthanized 24 h after these treatments and samples of draining lymph node and treated ear were collected for examination. The PDT group showed lower bacterial load in the draining lymph node when compared to the saline and curcumin groups (p-value <0.05) 24 h after treatment. In addition to bacterial load, the PDT group presented a higher concentration of nitrates and nitrites in the draining lymph node when compared to the saline and curcumin groups (p-value <0.001). Examining the infectious site, despite apparently having similar inflammatory cell recruitment compared with the control groups, the PDT group showed a profile with less intense activity in the myeloperoxidase expression when compared to the saline group (p-value <0.001). Additionally, the detected concentration of cytokines such as IL-1ß, IL-12, and IL-10 was significantly lower in the PDT group when compared to the saline group (p-value <0.01; p-value <0.05; p-value <0.05, respectively), thus presenting a less intense inflammatory response during infection resolution. Our pilot study showed for the first time the therapeutic potential of PDT using curcumin when administered intradermally in the treatment of infections caused by S. aureus in mice with T1DM.

Lactiplantibacillus plantarum strains isolated from spontaneously fermented cocoa exhibit potential probiotic properties against Gardnerella vaginalis and Neisseria gonorrhoeae.

BACKGROUND: Probiotics are important tools in therapies against vaginal infections and can assist traditional antibiotic therapies in restoring healthy microbiota. Recent research has shown that microorganisms belonging to the genus Lactobacillus have probiotic potential. Thus, this study evaluated the potential in vitro probiotic properties of three strains of Lactiplantibacillus plantarum, isolated during the fermentation of high-quality cocoa, against Gardnerella vaginalis and Neisseria gonorrhoeae. Strains were evaluated for their physiological, safety, and antimicrobial characteristics. RESULTS: The hydrophobicity of L. plantarum strains varied from 26.67 to 91.67%, and their autoaggregation varied from 18.10 to 30.64%. The co-aggregation of L. plantarum strains with G. vaginalis ranged from 14.73 to 16.31%, and from 29.14 to 45.76% with N. gonorrhoeae. All L. plantarum strains could moderately or strongly produce biofilms. L. plantarum strains did not show haemolytic activity and were generally sensitive to the tested antimicrobials. All lactobacillus strains were tolerant to heat and pH resistance tests. All three strains of L. plantarum showed antimicrobial activity against the tested pathogens. The coincubation of L. plantarum strains with pathogens showed that the culture pH remained below 4.5 after 24 h. All cell-free culture supernatants (CFCS) demonstrated activity against the two pathogens tested, and all L. plantarum strains produced hydrogen peroxide. CFCS characterisation in conjunction with gas chromatography revealed that organic acids, especially lactic acid, were responsible for the antimicrobial activity against the pathogens evaluated. CONCLUSION: The three strains of L. plantarum presented significant probiotic characteristics against the two pathogens of clinical importance. In vitro screening identified strong probiotic candidates for in vivo studies for the treatment of vaginal infections.

Gardnerella vaginalis and Neisseria gonorrhoeae Are Effectively Inhibited by Lactobacilli with Probiotic Properties Isolated from Brazilian Cupuaçu (Theobroma grandiflorum) Fruit.

In recent years, certain Lactobacillus sp. have emerged in health care as an alternative therapy for various diseases. Based on this, this study is aimed at evaluating in vitro the potential probiotics of five lactobacilli strains isolated from pulp of cupuaçu fruit fermentation against Gardnerella vaginalis and Neisseria gonorrhoeae. Our lactobacilli strains were classified as safe for use in humans, and they were tolerant to heat and pH. Our strains were biofilm producers, while hydrophobicity and autoaggregation varied from 13% to 86% and 13% to 25%, respectively. The coaggregation of lactobacilli used in this study with G. vaginalis and N. gonorrhoeae ranged from 15% to 36% and 32% to 52%, respectively. Antimicrobial activity was present in all tested Lactobacillus strains against both pathogens, and the growth of pathogens in coculture was reduced by the presence of our lactobacilli. Also, all tested lactobacilli reduced the pH of the culture, even in incubation with pathogens after 24 hours. The cell-free culture supernatants (CFCS) of all five lactobacilli demonstrated activity against the two pathogens with a halo presence and CFCS characterization assay together with gas chromatography revealed that lactic acid was the most abundant organic acid in the samples (50% to 62%). Our results demonstrated that the organic acid production profile is strain-specific. This study revealed that cupuaçu is a promising source of microorganisms with probiotic properties against genital pathogens. We demonstrated by in vitro tests that our Lactobacillus strains have probiotic properties. However, the absence of in vivo tests is a limitation of our work due to the need to evaluate the interaction of our lactobacilli with pathogens in the vaginal mucosa. We believe that these findings may be useful in developing a product containing our lactobacilli and their supernatants in order to support with vaginal health.

Anticariogenic activities of Libidibia ferrea, gallic acid and ethyl gallate against Streptococcus mutans in biofilm model.

ETHNOPHARMACOLOGICAL RELEVANCE: In Brazil, ethnopharmacological studies show that Libidibia ferrea (Mart. ex Tul.) L. P. Queiroz is commonly used in folk medicine as an antifungal, antimicrobial and anti-inflammatory. In the Amazon region, the dried fruit powder of L. ferrea are widely used empirically by the population in an alcoholic tincture as an antimicrobial mouthwash in oral infections and the infusion is also recommended for healing oral wounds. However, there are few articles that have evaluated the antimicrobial activity against oral pathogens in a biofilm model, identifying active compounds and mechanisms of action. AIM OF THE STUDY: The aim of this study was to evaluate the antimicrobial and anti-adherence activities of the ethanolic extract, fractions and isolated compounds (gallic acid and ethyl gallate) of the fruit and seed of L. ferrea against Streptococcus mutans. The inhibition of acidicity/acidogenicity and the expression of the S. mutans GTF genes in biofilms were also evaluated. MATERIALS AND METHODS: Minimal Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and Minimum Inhibitory Concentration of Cell Adhesion (MICA) were evaluated with ethanolic extract (EELF), fractions, gallic acid (GA) and ethyl gallate (EG) against S. mutans. Inhibition of biofilm formation, pH drop and proton permeability tests were conducted with EELF, GA and EG, and also evaluated the expression of the GTF genes in biofilms. The compounds of dichloromethane fraction were identified by GC-MS. RESULTS: This is the first report of shikimic, pyroglutamic, malic and protocatechuic acids identified in L. ferrea. EELF, GA and EG showed MIC at 250 µg/mL, and MBC at 1000 µg/mL by EELF. EELF biofilms showed reduced dry weight and acidogenicity of S. mutans in biofilms. GA and EG reduced viable cells, glucans soluble in alkali, acidogenicity, aciduricity and downregulated expression of gtfB, gtfC and gtfD genes in biofilms. SEM images of GA and EG biofilms showed a reduction of biomass, exopolysaccharide and microcolonies of S. mutans. CONCLUSIONS: The ethanolic extract of fruit and seed of L. ferrea, gallic acid and ethyl gallate showed great antimicrobial activity and inhibition of adhesion, reduction of acidogenicity and aciduricity in S. mutans biofilms. The results obtained in vitro validate the use of this plant in ethnopharmacology, and open opportunities for the development of new oral anticariogenic agents, originated by plants that can inhibit pathogenic biofilm that leads to the development of caries.

Simultaneous circulation of zakat, dengue, and chikungunya viruses and their vertical co-transmission among Aedes aegypti.

The outbreaks caused by the Aedes aegypti-transmitted dengue virus (DENV), zakat virus (ZIKV), and chikungunya virus (CHIKV) result in a significant impact to the health systems of tropical countries. Furthermore, the occurrence of patients coinfected by at least two of these arboviruses is an aggravating factor in that scenario. On this basis, surveillance tools such as the Rapid Index Survey for Aedes aegypti (LIRAa) are used to estimate vector infestation in order to improve the prediction of human outbreaks. Ae. aegypti eggs were collected in the city of Vitória da Conquista, in Bahia State, Brazil, and subsequently hatched into larvae, which were analyzed in pools or individually for the presence of DENV, ZIKV, and CHIKV by molecular biology methods. The detection data for arboviruses were crossed with the LIRAa obtained in each region of the study city. Thirty larvae pools were analyzed, and fourteen (46.6%) of them were detected positive for DENV, ZIKV, and/or CHIKV. Among the individually analyzed larvae (n = 30), nine (30%) were positive for any of these arboviruses, and four (13.3%) were simultaneously coinfected by DENV and ZIKV. Furthermore, there was a positive correlation between the detection of circulating arboviruses and LIRAa. The simultaneous Ae. aegypti larvae infection by two different arboviruses is an unprecedented finding. This result suggests the occurrence of a vertical arboviruses co-transmission from the female mosquito to its offspring in nature. The occurrence of concomitant circulation of DENV, ZIKV, and CHIKV in Ae. aegypti from a single study region is another finding of this article. Finally, LIRAa seems to not only estimate vector infestation but also to predict circulation of arboviruses.

High-intensity interval training is more effective than continuous training to reduce inflammation markers in female rats with cisplatin nephrotoxicity.

AIMS: Cisplatin (CP) is an antineoplastic widely used in the treatment of various solid tumors, however, its clinical application is limited by nephrotoxicity. Here, we compared the impact of preconditioning with high-intensity interval training (HIIT) with continuous training of low (LIT) and moderate (MIT) intensity on innate immunity markers in female rats with CP-induced acute kidney injury. MATERIALS AND METHODS: The rats were divided into five groups (n = 7): saline control and sedentary (C + S); CP and sedentary (CP + S); CP and LIT (CP + LIT); CP and MIT (CP + MIT) and CP and HIIT (CP + HIIT). The training intensity was determined by a maximum running test. At the end of training, the rats received a single dose of CP (5 mg/kg), and 7 days later they were euthanized. We evaluated renal function parameters (serum creatinine, glomerular filtration rate and proteinuria), renal structure, macrophage tissue infiltration, immunolocalization of nuclear transcription factor kappa B (NF-κB), renal levels of tumor necrosis factor-alpha (TNF-α), interleukin 1ß (IL-1ß), and interleukin 6 (IL-6), and gene expression of monocyte chemoattractant protein-1 (MCP-1), toll-like receptor 4 (TLR4), and NF-κB in renal tissue. KEY FINDINGS: Although both MIT and HIIT attenuated the degree of renal injury, only the HIIT prevented changes in renal function. The three training protocols mitigated the increase in expression of all inflammatory markers, however, this effect was more pronounced in HIIT. SIGNIFICANCE: All training protocols promoted renoprotective actions, but HIIT was more effective in mitigating CP-induced acute kidney injury, in part by modulation of important markers of the innate immune response.

Tempol reduces inflammation and oxidative damage in cigarette smoke-exposed mice by decreasing neutrophil infiltration and activating the Nrf2 pathway.

Cigarette smoke is a complex mixture capable of triggering inflammation and oxidative damage in animals at pulmonary and systemic levels. Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) reduces tissue injury associated with inflammation in vivo by mechanisms that are not completely understood. Here we evaluated the effect of tempol on inflammation and oxidative damage induced by acute exposure to cigarette smoke in vivo. Male C57BL/6 mice (n = 32) were divided into 4 groups (n = 8 each): 1) control group exposed to ambient air (GC), 2) animals exposed to cigarette smoke for 5 days (CSG), mice treated 3) prior or 4) concomitantly with tempol (50 mg/kg/day) and exposed to cigarette smoke for 5 days. The results showed that the total number of leukocytes and neutrophils increased in the respiratory tract and lung parenchyma of mice exposed to cigarette smoke. Likewise, MPO levels and activity as well as lipid peroxidation and lung protein nitration and carbonylation also increased. Administration of tempol before or during exposure to cigarette smoke inhibited all the above parameters. Tempol also reduced the pulmonary expression of the inflammatory cytokines Il-6, Il-1ß and Il-17 to basal levels and of Tnf-α by approximately 50%. In contrast, tempol restored Il-10 and Tgf-ß levels and enhanced the expression of Nrf2-associated genes, such as Ho-1 and Gpx2. Accordingly, total GPx activity increased in lung homogenates of tempol-treated animals. Taken together, our results show that tempol protects mouse lungs from inflammation and oxidative damage resulting from exposure to cigarette smoke, likely through reduction of leukocyte infiltration and increased transcription of some of the Nrf2-controlled genes.

Anthropometric indicators as screening tools for sarcopenia in older adult women.

OBJECTIVE: To investigate the association between sarcopenia and different anthropometric indicators, and identify the best indicator to discriminate sarcopenia in community-dwelling older adult women. METHOD: Data from 173 older adult women (≥60 years), living in Lafaiete Coutinho, a small-sized city in northeastern Brazil, were analyzed. Sarcopenia was defined based on the European consensus on definition and diagnosis using three components: muscle mass, muscle strength and performance. The association between sarcopenia and anthropometric indicators (body mass index, corrected arm muscle area and calf perimeter) was tested using the binary logistic regression technique. RESULTS: The adjusted regression model indicated that all anthropometric indicators were inversely associated with sarcopenia, and an increase by one unit in body mass index, corrected arm muscle area or calf circumference decreased the probability of sarcopenia in older adult women by approximately 85%, 16% and 72%, respectively. CONCLUSION: All the studied anthropometric indicators can be used as discriminators of sarcopenia in an older adult women population. To this end body mass index exhibited better sensitivity and calf circumference better specificity. The results of the study may improve nursing practice and that of other healthcare professionals, enabling sarcopenia screening in older adult women from simple and low-cost anthropometric indicators.