Brazilian Journal of Medical and Biological Research, Volume: 50, Issue: 7, Published: 2017
  • Is there a role for voltage-gated Na+ channels in the aggressiveness of breast cancer? Reviews

    Rhana, P.; Trivelato, R.R.; Beirão, P.S.L.; Cruz, J.S.; Rodrigues, A.L.P.

    Abstract in English:

    Breast cancer is the most common cancer among women and its metastatic potential is responsible for numerous deaths. Thus, the need to find new targets for improving treatment, and even finding the cure, becomes increasingly greater. Ion channels are known to participate in several physiological functions, such as muscle contraction, cell volume regulation, immune response and cell proliferation. In breast cancer, different types of ion channels have been associated with tumorigenesis. Recently, voltage-gated Na+ channels (VGSC) have been implicated in the processes that lead to increased tumor aggressiveness. To explain this relationship, different theories, associated with pH changes, gene expression and intracellular Ca2+, have been proposed in an attempt to better understand the role of these ion channels in breast cancer. However, these theories are having difficulty being accepted because most of the findings are contrary to the present scientific knowledge. Several studies have shown that VGSC are related to different types of cancer, making them a promising pharmacological target against this debilitating disease. Molecular biology and cell electrophysiology have been used to look for new forms of treatment aiming to reduce aggressiveness and the disease progress.
  • Pain and distress outcomes in infants and children: a systematic review Reviews

    Oliveira, N.C.A.C.; Gaspardo, C.M.; Linhares, M.B.M.

    Abstract in English:

    The aim of the present study was to systematically review the recent literature about pain and distress outcomes in children and critically analyze the methodological quality of the reports. The systematic review was based on the PRISMA statement and performed by selecting articles that are indexed in scientific databases. The methodological quality of reports was examined using STROBE statement, for observational studies, and CONSORT statement, for randomized controlled trials. The PedIMMPACT consensus was used to evaluate the psychometric quality of pain instruments. We analyzed 23 empirical studies, including 14 randomized controlled trials, seven cross-sectional studies, and two studies with cohort designs. Fourteen studies included preschool- and schoolchildren, and nine studies included infants. Regarding studies with infants, pain responses were evaluated by heart rate, crying and behavioral observation scales, and distress was evaluated only by salivary cortisol. Four-handed care and sensorial saturation interventions were used to evaluate efficacy to reduce pain and distress responses. Concerning studies with children, both pain and distress responses were evaluated by self- and hetero-reports, behavioral observation and/or physiological measures. Distraction was effective for reducing pain and distress during burn dressing changes and needle procedures, and healing touch intervention reduced distress and pain in chronic patients. All of the studies scored at least 60% in the methodological quality assessment. The pain outcomes included measures of validity that were classified as well-established by the PedIMMPACT. This systematic review gathers scientific evidence of distress-associated pain in children. Pain and distress were measured as distinct constructs, and their associations were poorly analyzed.
  • Effects of heme oxygenase-1 recombinant Lactococcus lactis on the intestinal barrier of hemorrhagic shock rats Biomedical Sciences

    Gao, X.Y.; Zhou, X.F.; Wang, H.; Lv, N.; Liu, Y.; Guo, J.R.

    Abstract in English:

    This study aimed to investigate the effects of heme oxygenase-1 recombinant Lactococcus lactis (LL-HO-1) on the intestinal barrier of rats with hemorrhagic shock. One hundred Sprague-Dawley male rats (280–320 g) were randomly divided into healthy control group (N group) and hemorrhagic shock group (H group). Each group was subdivided into HO1t, HO2t, HO3t, PBS and LL groups in which rats were intragastrically injected with LL-HO-1 once, twice and three times, PBS and L. lactis (LL), respectively. The mortality, intestinal myeloperoxidase (MPO) activity, intestinal contents of TNF-α, IL-10 and HO-1, and intestinal Chiu's score were determined. Results showed that in N group, the HO-1 content increased after LL-HO-1 treatment, and significant difference was observed in HO1t group and HO2t group (P<0.05). In H groups, MPO activity and Chiu's score decreased, but IL-10 content increased in LL-HO-1-treated groups when compared with PBS and LL groups (P<0.05). When compared with N group, the MPO activity reduced dramatically in LL-HO-1-treated groups. Thus, in healthy rats (N group), intragastrical LL-HO-1 treatment may increase the intestinal HO-1 expression, but has no influence on the intestinal barrier. In hemorrhagic shock rats, LL-HO-1 may significantly protect the intestinal barrier, and repeating the intragastrical LL-HO-1 treatments twice has the most obvious protection.
  • Presence of t(14;18) translocation in healthy individuals varies according to ethnic background in the Brazilian population Biomedical Sciences

    Levy, D.; Bertoldi, E.R.M.; Ruiz, J.L.M.; Pereira, J.; Bydlowski, S.P.

    Abstract in English:

    Several groups have demonstrated that healthy individuals can present the t(14;18) translocation. In this report, the presence of the translocation was examined in healthy blood donors in Brazil, a country considered an ethnic melting pot. The translocation was detected by nested PCR in 227 peripheral blood samples from individuals with different ethnic backgrounds. The t(14;18) translocation was found in 45 of 85 White individuals (52.94%); in 57 of 72 Black individuals (79.17%); and in 68 of 70 individuals (97.14%) of Japanese-descent. In conclusion, the frequency of the t(14;18) translocation in the Brazilian population varies according to the ethnic background.
  • An ontogenic study of the behavioral effects of chronic intermittent exposure to ayahuasca in mice Biomedical Sciences

    Correa-Netto, N.F.; Masukawa, M.Y.; Nishide, F.; Galfano, G.S.; Tamura, F.; Shimizo, M.K.; Marcato, M.P.; Santos, J.G.; Linardi, A.

    Abstract in English:

    Ayahuasca is a beverage obtained from decoctions of the Banisteriopsis caapi plus Psychotria viridis. In religious contexts, ayahuasca is used by different age groups. However, little is known of the effects of ayahuasca during ontogenic development, particularly with regard to the functional characteristics of the central nervous system. Animal models are useful for studying the ontogenic effects of ayahuasca because they allow exclusion of the behavioral influence associated with the ritualistic use. We investigated the effects of exposure to ayahuasca (1.5 mL/kg, orally, twice a week) on memory and anxiety in C57BL/6 mice, with the post-natal day (PND) being used as the ontogenic criterion for classification: childhood (PND21 to PND35), adolescence (PND35 to PND63), adulthood (PND90-PND118), childhood-adolescence (PND21 to PND63), childhood-adulthood (PND21 to PND118) and adolescence-adulthood (PND35 to PND118). One day after the last ayahuasca exposure, the mice were subjected to the Morris water maze (MWM), open field and elevated plus maze tasks (EPM). Ayahuasca did not affect locomotion in the open field or open arms exploration in the EPM, but increased the risk assessment behavior in the childhood group. Ayahuasca did not cause any change in acquisition of spatial reference memory in the MWM task, but decreased the time spent on the platform quadrant during the test session in the adolescence group. These results suggest that, in mice, exposure to ayahuasca in childhood and adolescence promoted anxiety and memory impairment, respectively. However, these behavioral changes were not long-lasting since they were not observed in the childhood-adulthood and adolescence-adulthood groups.
  • Chronic intermittent exposure to ayahuasca during aging does not affect memory in mice Biomedical Sciences

    Correa-Netto, N.F.; Coelho, L.S.; Galfano, G.S.; Nishide, F.; Tamura, F.; Shimizu, M.K.; Santos, J.G.; Linardi, A.

    Abstract in English:

    The Quechua term ayahuasca refers to a beverage obtained from decoctions of the liana Banisteriopsis caapi with leaves of Psychotria viridis. The ritualistic use of ayahuasca is becoming a global phenomenon, with some individuals using this beverage throughout life, including in old age. Cognitive impairment is a common manifestation during aging. There are conflicting reports on the ability of some ayahuasca compounds to exert neuroprotective or neurotoxic effects that could improve or impair learning and memory. Animal models provide a relevant and accessible means of investigating the behavioral effects of ayahuasca without the environmental conditions associated with the ritualistic use of the beverage. In this study, we investigated the influence of chronic ayahuasca exposure throughout aging on the spatial reference and habituation memories of mice. Twenty-eight male c57bl/6 mice (6 months old) received ayahuasca or water (1.5 mL/kg, orally) twice a week for 12 months and were tested in the Morris water maze (MWM), open field and elevated plus maze (EPM) tasks before and after treatment. During aging, there was significant impairment in the evocation (but not acquisition) of spatial reference memory and in habituation to the open field. There was also a decrease in locomotor activity in the open field and EPM tests, whereas the anxiety parameters were unaltered. Ayahuasca treatment did not alter any of these parameters associated with aging. These findings indicate that chronic exposure to ayahuasca during aging did not affect memory in mice.
  • Increased expression of ID2, PRELP and SMOC2 genes in patients with endometriosis Biomedical Sciences

    Araujo, F.M.; Meola, J.; Rosa-e-Silva, J.C.; Paz, C.C.P.; Ferriani, R.A.; Nogueira, A.A.

    Abstract in English:

    Endometriosis is a benign, estrogen-dependent disease with symptoms such as pelvic pain and infertility, and it is characterized by the ectopic distribution of endometrial tissue. The expression of the ID2, PRELP and SMOC2 genes was compared between the endometrium of women without endometriosis in the proliferative phase of their menstrual cycle and the eutopic and ectopic endometrium of women with endometriosis in the proliferative phase. Paired tissue samples from 20 women were analyzed: 10 from endometrial and peritoneal endometriotic lesions and 10 from endometrial and ovarian endometriotic lesions. As controls, 16 endometrium samples were collected from women without endometriosis in the proliferative phase of menstrual cycle. Analysis was performed by real-time polymerase chain reaction (PCR). There was no significant difference between gene expression in the endometrium of women with and without endometriosis. The ID2 gene expression was increased in the most advanced stage of endometriosis and in ovarian endometriomas, the PRELP was more expressed in peritoneal lesions, and the SMOC2 was highly expressed in both peritoneal and endometrioma lesions. Considering that the genes studied participate either directly or indirectly in cellular processes that can lead to cell migration, angiogenesis, and inappropriate invasion, it is possible that the deregulation of these genes caused the development and maintenance of ectopic tissue.
  • microRNA-142-3p inhibits apoptosis and inflammation induced by bleomycin through down-regulation of Cox-2 in MLE-12 cells Biomedical Sciences

    Guo, F.; Lin, S.C.; Zhao, M.S.; Yu, B.; Li, X.Y.; Gao, Q.; Lin, D.J.

    Abstract in English:

    microRNA (miR)-142-3p is implicated in malignancy and has been identified as a biomarker for aggressive and recurrent lung adenocarcinomas. This study aimed to evaluate the inhibitory effect of miR-142-3p on apoptosis and inflammation induced by bleomycin in MLE-12 cells. MLE-12 cells were first transfected either with miR-142-3p mimic or miR-142-3p inhibitor and then the cells were exposed to 50 μg/mL of bleomycin. Thereafter, cell viability, apoptosis and the expression of pro-inflammatory cytokines were assessed using CCK-8, flow cytometry, RT-PCR and western blot analyses. Cox-2, PI3K, AKT and mTOR expressions were detected by western blotting after bleomycin was administered together with NS-398 (an inhibitor of Cox-2). As a result, cell viability was significantly decreased, as well as apoptosis and the expression of IL-1 and TNF-α were remarkably increased after 50 and 100 μg/mL of bleomycin administration. miR-142-3p overexpression alleviated bleomycin-induced apoptosis and overproduction of these two pro-inflammatory cytokines, while miR-142-3p suppression exhibited completely opposite results. Up-regulation of Cox-2 and inactivation of PI3K/AKT/mTOR were found in bleomycin-pretreated cells, while these abnormal regulations were partially abolished by miR-142-3p overexpression and NS-398. In conclusion, this study demonstrated that miR-142-3p overexpression protected bleomycin-induced injury in lung epithelial MLE-12 cells, possibly via regulating Cox-2 expression and PI3K/AKT/mTOR signaling pathway. These findings provide evidence that miR-142-3p may be a therapeutic strategy for idiopathic pulmonary fibrosis (IPF) treatment.
  • Two novel Co(II) complexes with two different Schiff bases: inhibiting growth of human skin cancer cells Biomedical Sciences

    Xiao, Y.-J.; Diao, Q.-C.; Liang, Y.-H.; Zeng, K.

    Abstract in English:

    Using two flexible Schiff bases, H2L1 and H2L2, two new cobalt II (Co(II))-coordination compounds, namely, Py3CoL1 (1) and Py3CoL2 (2) (Py=pyridine, L1=3,5-ClC6H2(O)C=NC6H3(O)-4-NO2, L2=3,5-BrC6H2(O)C=NC6H3(O)-4-NO2) have been synthesized under solvothermal conditions. Single crystal X-ray structural analysis revealed that compounds 1 and 2 are both six-coordinate in a distorted octahedral geometry, and the 1D chain structure was formed by the π…π and C-H…O interactions or C-H…Cl interaction. The in vitro antitumor activities of 1, 2 and their corresponding organic ligands Py, L1, and L2 were studied and evaluated, in which three human skin cancer cell lines (A-431, HT-144 and SK-MEL-30) were used in the screening tests.
  • Cantharidin suppressed breast cancer MDA-MB-231 cell growth and migration by inhibiting MAPK signaling pathway Biomedical Sciences

    Gu, X.-D.; Xu, L.-L; Zhao, H.; Gu, J.-Z; Xie, X.-H

    Abstract in English:

    As an active constituent of the beetle Mylabris used in traditional Chinese medicine, cantharidin is a potent and selective inhibitor of protein phosphatase 2A (PP2A) that plays a crucial role in cell cycle progression, apoptosis, and cell fate. The role and possible mechanisms exerted by cantharidin in cell growth and metastasis of breast cancer were investigated in this study. Cantharidin was found to inhibit cell viability and clonogenic potential in a time- and dose-dependent manner. Cell cycle analysis revealed that cell percentage in G2/M phase decreased, whereas cells in S and G1 phases progressively accumulated with the increasing doses of cantharidin treatment. In a xenograft model of breast cancer, cantharidin inhibited tumor growth in a dose-dependent manner. Moreover, high doses of cantharidin treatment inhibited cell migration in wound and healing assay and downregulated protein levels of major matrix metalloproteinases (MMP)-2 and MMP-9. MDA-MB-231 cell migration and invasion were dose-dependently inhibited by cantharidin treatment. Interestingly, the members of the mitogen-activated protein kinase (MAPK) signaling family were less phosphorylated as the cantharidin dose increased. Cantharidin was hypothesized to exert its anticancer effect through the MAPK signaling pathway. The data of this study also highlighted the possibility of using PP2A as a therapeutic target for breast cancer treatment.
  • Penetration of 0.3% ciprofloxacin, 0.3% ofloxacin, and 0.5% moxifloxacin into the cornea and aqueous humor of enucleated human eyes Biomedical Sciences

    Silva, G.C.M.; Jabor, V.A.P.; Bonato, P.S.; Martinez, E.Z.; Faria-e-Sousa, S.J.

    Abstract in English:

    We aimed to quantify the penetration of ciprofloxacin, ofloxacin, and moxifloxacin into the cornea and aqueous humor of cadaver eyes. A total of 60 enucleated eyes, not eligible for corneal transplantation, were divided into three groups and immersed in commercial solutions of 0.3% ciprofloxacin, 0.3% ofloxacin, or 0.5% moxifloxacin for 10 min. Whole corneas and samples of aqueous humor were then harvested and frozen, and drug concentrations analyzed by liquid chromatography tandem mass spectrometry. The mean corneal concentration of moxifloxacin was twice as high as ofloxacin, and the latter was twice as high as ciprofloxacin. The mean concentration of moxifloxacin in the aqueous humor was four times higher than the other antibiotics, and the mean concentrations of ciprofloxacin and ofloxacin were statistically similar. The amount of drug that penetrated the anterior chamber after a 10-min immersion was far below the safe limit of endothelial toxicity of each preparation. Moxifloxacin demonstrated far superior penetration into the cornea and anterior chamber of cadaver eyes compared to ciprofloxacin and ofloxacin. One should not expect endothelial toxicity with the commercial eye drops of ciprofloxacin, ofloxacin, and moxifloxacin that reach the anterior chamber through the cornea.
  • Extracellular diffusion quantified by magnetic resonance imaging during rat C6 glioma cell progression Biomedical Sciences

    Song, G.; Luo, T.; Dong, L.; Liu, Q.

    Abstract in English:

    Solution reflux and edema hamper the convection-enhanced delivery of the standard treatment for glioma. Therefore, a real-time magnetic resonance imaging (MRI) method was developed to monitor the dosing process, but a quantitative analysis of local diffusion and clearance parameters has not been assessed. The objective of this study was to compare diffusion into the extracellular space (ECS) at different stages of rat C6 gliomas, and analyze the effects of the extracellular matrix (ECM) on the diffusion process. At 10 and 20 days, after successful glioma modeling, gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) was introduced into the ECS of rat C6 gliomas. Diffusion parameters and half-life of the reagent were then detected using MRI, and quantified according to the mathematical model of diffusion. The main ECM components [chondroitin sulfate proteoglycans (CSPGs), collagen IV, and tenascin C] were detected by immunohistochemical and immunoblot analyses. In 20-day gliomas, Gd-DTPA diffused more slowly and derived higher tortuosity, with lower clearance rate and longer half-life compared to 10-day gliomas. The increased glioma ECM was associated with different diffusion and clearance parameters in 20-day rat gliomas compared to 10-day gliomas. ECS parameters were altered with C6 glioma progression from increased ECM content. Our study might help better understand the glioma microenvironment and provide benefits for interstitial drug delivery to treat brain gliomas.
  • Long-term effects of human amniotic membrane in a rat model of biliary fibrosis Biomedical Sciences

    Sant'Anna, L.B.; Brito, F.S.; Barja, P.R.; Nicodemo, M.C.

    Abstract in English:

    Liver fibrosis is the most common outcome of chronic liver diseases, and its progression to cirrhosis can only be effectively treated with liver transplantation. The amniotic membrane (AM) has been studied as an alternative therapy for fibrosis diseases mainly for its favorable properties, including anti-inflammatory, anti-scaring and immunomodulatory properties. It was recently demonstrated that the AM reduces the progression of biliary fibrosis to its advanced stage, cirrhosis, when applied on the liver for 6 weeks after fibrosis induction. Here, we investigated the effects of AM on rat fibrotic liver, during a prolonged period of time. Fibrosis was induced by bile duct ligation (BDL), and at the same time, a fragment of AM was applied around the liver. After 1, 3, 6, and 9 weeks, the degree of fibrosis was assessed by qualitative Knodell scoring, and by quantitative image analysis to quantify the area of collagen deposition in hepatic tissue. While fibrosis progressed rapidly in untreated BDL animals, leading to cirrhosis within 6 weeks, AM-treated livers showed confined fibrosis at the periportal area with few and thin fibrotic septa, but without cirrhosis. In addition, collagen deposition was reduced to about 36 and 55% of levels observed in BDL at 6 and 9 weeks after BDL, respectively, which shows that the longer the period of AM application, the lower the collagen deposition. These results suggested that AM applied as a patch onto the liver surface for longer periods attenuated the severity of biliary fibrosis and protected against liver degeneration caused by excessive collagen deposition.
  • Identification of IgE and IgG1 specific antigens in Echinococcus granulosus cyst fluid Clinical Investigation

    Li, S.; Qian, R.; Wang, S.; Ye, J.; Zheng, H.

    Abstract in English:

    Cystic echinococcosis (CE) is an anthropozoonotic disease with worldwide distribution and is caused by the cestode Echinococcus granulosus. Anaphylactic shock induced by CE rupture is a serious complication especially in patients with hydatid infections, as the resulting leakage of fluid contains highly toxic endogenous antigen. We aimed to isolate and identify the antigens of specific IgE and IgG1 (sIgE and sIgG1) in E. granulosus cyst fluid (EgCF). Crude antigen for EgCF was prepared from E. granulosus-infected sheep liver. Antigens were separated and identified by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (1D SDS-PAGE), two-dimensional gel electrophoresis (2-DE), and immunoblotting. Results of 1D SDS-PAGE and immunoblotting showed that 40.5 kDa protein was the major antigen of sIgE, and 35.5 kDa protein was the major antigen of sIgG1 in EgCF. Results of 2-DE and immunoblotting showed that main antigens of sIgE in EgCF were four proteins with pI values ranging from 6.5 to 9.0 and a molecular weight of 40.5 kDa. Main antigens of sIgG1 in EgCF were five proteins with pI values ranging from 6.5 to 9.0 and a molecular weight of 35.5 kDa. The antigens identified for sIgE and sIgG1 can provide critical insights into cellular and molecular mechanisms underlying anaphylactic shock induced by CE.
  • Erratum for: Primary cultures of mouse small intestinal epithelial cells using the dissociating enzyme type I collagenase and hyaluronidase Correction

  • Retraction notice for: Characteristics of liver fibrosis with different etiologies using a fully quantitative fibrosis assessment tool [Braz J Med Biol Res (2017) 50(6): e5234] Retraction

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