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Brazilian Journal of Medical and Biological Research, Volume: 53, Número: 8, Publicado: 2020
  • Biomechanical and biochemical investigation of erythrocytes in late stage human leptospirosis Research Article

    Silva, J.A.X.; Albertini, A.V.P.; Fonseca, C.S.M.; Silva, D.C.N.; Carvalho, V.C.O.; Lima, V.L.M.; Fontes, A.; Costa, E.V.L.; Nogueira, R.A.

    Resumo em Inglês:

    Leptospirosis is a zoonotic disease caused by bacteria of the genus Leptospira, which can cause lipid changes in the erythrocyte membrane. Optical tweezers were used to characterize rheological changes in erythrocytes from patients with leptospirosis in the late stage. Biochemical methods were also used for quantification of plasma lipid, erythrocyte membrane lipid, and evaluation of liver function. Our data showed that the mean elastic constant of erythrocytes from patients with leptospirosis was around 67% higher than the control (healthy individuals), indicating that patient’s erythrocytes were less elastic. In individuals with leptospirosis, several alterations in relation to control were observed in the plasma lipids, however, in the erythrocyte membrane, only phosphatidylcholine showed a significant difference compared to control, increasing around 41%. With respect to the evaluation of liver function of individuals with leptospirosis, there was a significant increase in levels of alanine transaminase (154%) and aspartate transaminase (150%), whereas albumin was 43.8% lower than control (P<0.01). The lecithin-cholesterol acyltransferase fractional activity was 3.6 times lower in individuals with leptospirosis than in the healthy individuals (P<0.01). The decrease of the erythrocyte elasticity may be related to the changes of erythrocyte membrane phospholipids composition caused by disturbances that occur during human leptospirosis, with phosphatidylcholine being a strong candidate in the erythrocyte rheological changes.
  • Temporomandibular inflammation mobilizes parvalbumin and FosB/deltaFosB neurons of amygdala and dorsal raphe Research Article

    Nascimento, G.C.; de Paula, B.B.; Lowry, C.A.; Leite-Panissi, C.R.A.

    Resumo em Inglês:

    Pathophysiological mechanisms involved in orofacial pain and their relationship with emotional disorders have emerged as an important research area for multidisciplinary studies. In particular, temporomandibular disorders (TMD) have been evaluated clinically from both physiological and psychological perspectives. We hypothesized that an altered neuronal activity occurs in the amygdala and the dorsal raphe nucleus (DR), encephalic regions involved in the modulation of painful and emotional information. Adult male Wistar rats were used in an experimental complete Freund's adjuvant (CFA)-induced temporomandibular joint (TMJ) inflammation model. CFA was applied for 1 or 10 days, and the animals were euthanized for brain samples dissection for FosB/ΔFosB and parvalbumin (PV) immunostaining. Our results were consistent in showing that the amygdala and DR were activated in the persistent inflammatory phase (10 days) and that the expression of PV+ interneurons in the amygdala was decreased. In contrast, in the DR, the expression of PV+ interneurons was increased in persistent states of CFA-induced TMJ inflammation. Moreover, at 10 days of inflammation, there was an increased co-localization of PV+ and FosB/ΔFosB+ neurons in the basolateral and central nucleus of the amygdala. Different nuclei of the amygdala, as well as portions of the DR, were activated in the persistent phase (10 days) of TMJ inflammation. In conclusion, altered activity of the amygdala and DR was detected during persistent inflammatory nociception in the temporomandibular joint. These regions may be essential for both sensory and affective dimensions of orofacial pain.
  • Subjective time under altered states of consciousness in ayahuasca users in shamanistic rituals involving music Research Article

    Campagnoli, A.P.S.; Pereira, L.A.S.; Bueno, J.L.O.

    Resumo em Inglês:

    Ayahuasca is described as a hallucinogenic substance whose property is to alter the subjective experience of time and impair the perception of the passage of time during stimuli of more than two to three seconds. The dose-dependent effects of two concentrations of ayahuasca in the ritualistic context were investigated employing temporal reproduction tasks in participants experienced in shamanistic ayahuasca rituals. The study was conducted on nine healthy volunteers who ingested two doses of ayahuasca at two times during a ritual session. The doses of each session, consumed in amounts ranging from 20 to 60 mL, were either of low concentration or of experimental ayahuasca according to a double-blind procedure. Participants performed the task of immediately listening and reproducing, with a laptop, 20-s musical stimuli during the session. The results showed that significant temporal distortion was triggered by the musical stimulus presented without the ingestion of ayahuasca, with means of 16.33 to 16.52 s. There were minor temporal distortions after ingestion of ayahuasca: a mean of 17.91 s for control ayahuasca and of 18.38 s for experimental ayahuasca. These results with less temporal distortion among participants with ayahuasca intake disagree with other studies of hallucinogens involving temporal reproduction.
  • Modulation of Wnt/β-catenin signaling in IL-17A-mediated macrophage polarization of RAW264.7 cells Research Article

    Yuan, Chao; Yang, Dandan; Ma, Jia; Yang, Jiali; Xue, Jing; Song, Fuyang; Liu, Xiaoming

    Resumo em Inglês:

    Macrophages play pivotal roles in host defense and immune homeostasis, which have two major functional polarization states, the classically activated M1 and the alternatively activated M2. Interleukin (IL)-17A is an immune modulator able to shape macrophage phenotypes. Wnt/β-catenin is a developmental signaling pathway that plays crucial roles in morphogenesis and tissue homeostasis, which has also been recently demonstrated playing roles in immune regulation. A growing amount of evidence suggests that both Wnt and IL-17A signaling are involved in macrophage polarization. However, their interaction in macrophage polarization remains elusive. The aim of present study was to explore impacts of Wnt/β-catenin on IL-17A-mediated macrophage M1/M2 polarization in murine monocyte/macrophage-like cell line RAW264.7. Results revealed that IL-17A activated Wnt/β-catenin signaling and induced macrophage M1 polarization, but inhibited M2 polarization. In contrast, the activation of Wnt/β-catenin signaling led to the inhibition of M1 macrophage polarization but the promotion of M2 polarization. Importantly, the activation of Wnt/β-catenin also showed abilities to inhibit the IL-17A-induced M1 macrophage polarization while diminishing the IL-17A-inhibited M2 polarization. Molecular analysis further uncovered that the JAK/STAT signaling pathway was involved in the interaction of Wnt/β-catenin and IL-17A in the modulation of macrophage polarization. These results suggested that the Wnt/β-catenin signaling modulated IL-17A-altered macrophage polarization in part by regulating the JAK/STAT signaling pathway. This study thus revealed a novel function of Wnt/β-catenin signaling in regulating IL-17A-altered macrophage polarization.
  • Low expression of microRNA-328 can predict sepsis and alleviate sepsis-induced cardiac dysfunction and inflammatory response Research Article

    Sun, Bin; Luan, Chunye; Guo, Lisha; Zhang, Bing; Liu, Yufang

    Resumo em Inglês:

    Sepsis often leads to cardiac dysfunction and inflammation. This study investigated the clinical value of microRNA-328 (miR-328) in sepsis and its role in cardiac dysfunction and inflammation caused by sepsis. The expression level of miR-328 in the serum of the subjects was detected by qRT-PCR. Receiver operating characteristic (ROC) curve measured the diagnostic value of miR-328 in sepsis. Rat sepsis model was established to detect left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), and maximal rate of increase/decrease of left ventricular pressure (±dp/dtmax). Myocardial injury markers serum cardiac troponin I (cTnI), myocardial kinase isoenzyme (CK-MB), and inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). miR-328 expression was assessed in serum of sepsis patients and in rat models of sepsis. The AUC of ROC curve was 0.926, sensitivity 87.60%, and specificity 86.36%. Compared with the sham group, LVSP and +dp/dtmax were decreased in the rat model of sepsis. LVEDP, -dp/dtmax, cTnI, CK-MB, tumor necrosis factor-α, interleukin (IL)-6, and IL-1β were upregulated in the rat model of sepsis. The low expression of miR-328 reversed these indicators. miR-328 is a diagnostic marker for patients with sepsis, and decreasing the expression level of miR-328 can ameliorate cardiac dysfunction and cardiac inflammation in sepsis.
  • A method to assess heart rate variability in neonate rats: validation in normotensive and hypertensive animals Research Article

    Freitas, S.C.F.; dos Santos, C. Paixão; Arnold, A.; Stoyell-Conti, F.F.; Dutra, M.R.H.; Veras, M.; Irigoyen, M.C.; De Angelis, K.

    Resumo em Inglês:

    Several studies have focused on the heart rate variability (HRV) of murine species, while studies discussing HRV in murine neonates and infants remain scarce, since recording hemodynamic signals through invasive methods in small animals has been found to be quite challenging. Thus, this study aimed at describing and validating a novel method to assess HRV in newborn rats. An electrocardiogram (ECG) system was used to determine RR intervals in awake newborns and evaluate HRV in normotensive (Wistar) and hypertensive (SHR) neonate rats. After birth, ECG was recorded in the awake newborns, and they were allowed to rest on a heated surface, restricted only by the weight of the adhesive ECG electrodes. The electrodes were cut and adapted to provide more comfort to the animal, and gently placed on the newborn's skin. RR intervals were recorded over a 30-min period using an ECG system together with LabChart software (4 KHz). Three sequences of 5 min each from the ECG recording period were analyzed in time and frequency domains, using CardioSeries software. ECG data resulted in a clearly interpretable signal that was used to generate an RR interval sequence through time for the analysis of HRV. SHR neonates presented increased cardiac sympathovagal balance compared to Wistar neonates (low frequency/high frequency: 3.85±0.71 vs 0.90±0.09). In conclusion, the ECG setup here described may be used to record RR intervals to assess HRV in neonate rats, thus detecting early impairment of HRV in hypertensive newborns.
  • Treatment with zolpidem after ethanol administration potentiates the expression of ethanol-induced behavioral sensitization in mice Research Article

    Brandão, N.R.N.; Libarino-Santos, M.; Marinho, E.A.V.; Oliveira, T.S.; Borges, A.L.N.; Oliveira, A.P.; Oliveira-Campos, D.; Azevedo-Souza, N.; Santos, V.F.L.; Berro, L.F.; Oliveira-Lima, A.J.

    Resumo em Inglês:

    Contradictory findings suggest that the behavioral and abuse-related effects of ethanol are mediated by its action at α1 subunit-containing GABAA (α1GABAA) receptors. In the present study, we investigated the effects of a sub-chronic post-ethanol administration treatment with zolpidem, an α1-preferring positive allosteric modulator at GABAA receptors, on the subsequent expression of ethanol-induced behavioral sensitization in mice. Animals received ethanol (1.8 g/kg, ip) or saline treatments every other day for 15 days (8 treatment sessions) and were subsequently treated with zolpidem (0.5 mg/kg, ip) or vehicle 4 times on alternate days. At the end of the treatment phase, animals were challenged with saline or ethanol on separate days for the evaluation of the expression of conditioned locomotion and behavioral sensitization. Eight-day treatment with ethanol did not lead to the development of ethanol-induced behavioral sensitization. Animals treated with ethanol and subsequently administered vehicle showed similar locomotion frequencies during the last ethanol challenge compared to the control group receiving ethanol for the first time. Animals treated with ethanol and subsequently administered zolpidem expressed behavioral sensitization to ethanol during the ethanol challenge. The present study adds to the literature by providing further evidence of a role of α1GABAA receptors on the behavioral effects of ethanol. Because of the current highly prevalent co-abuse of ethanol and benzodiazepine drugs in humans, the use of zolpidem and other α1GABAA receptor ligands during ethanol withdrawal should be monitored carefully.
  • Long non-coding RNA LINC01268 promotes cell growth and inhibits cell apoptosis by modulating miR-217/SOS1 axis in acute myeloid leukemia Research Article

    Chen, Beili; Li, Yuchuan; Nie, Yuwei; Tang, Ailin; Zhou, Qin

    Resumo em Inglês:

    The aim of this study was to evaluate the pathogenic role of newly identified long non-coding (lnc)-RNA LINCO1268 in acute myeloid leukemia (AML), and investigate its therapeutic potential. The expression level of LINC01268 in AML was measured by quantitative PCR (qPCR). The viability, cell cycle progression, and apoptosis of AML cells were measured by CCK-8 assay and flow cytometry, respectively. The interaction between LINC01268 and miR-217 were predicted by the miRDB website, and then verified by luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The relationship between miR-217 and SOS1 was predicted by TargetScan website, and verified by luciferase reporter assay. LINC01268 was significantly upregulated by 1.6 fold in bone marrow samples of AML patients, which was associated with poor prognosis. LINC01268 was also significantly upregulated in AML cells. LINC01268 knockdown inhibited viability and cell cycle progression but promoted apoptosis of AML cells. Furthermore, LINC01268 functioned as a ceRNA via competitively binding to miR-217, and SOS1 was identified as a target of miR-217. Moreover, LINC01268 positively regulated SOS1 expression to promote AML cell viability and cell cycle progression but inhibited apoptosis via sponging miR-217. LINC01268 promoted cell growth and inhibited cell apoptosis through modulating miR-217/SOS1 axis in AML. This study offers a novel molecular mechanism for a better understanding of the pathology of AML. LINC01268 could be considered as a potential biomarker for the therapy and diagnosis of AML.
  • Hyaluronic acid versus dexamethasone for the treatment of recurrent aphthous stomatitis in children: efficacy and safety analysis Research Article

    Yang, Zheng; Li, Miaojuan; Xiao, Lin; Yi, Zhiming; Zhao, Min; Ma, Shengjie

    Resumo em Inglês:

    The objective of this study was to compare the safety and efficacy of 0.2% hyaluronic acid (HA) topical gel and dexamethasone topical ointment in the treatment of recurrent aphthous ulcers (RAU) in children. This retrospective observational study included 104 patients who had more than two episodes of oral aphthous ulcers per year and were treated with HA (n=52) or dexamethasone (n=52) from August 15, 2014 to September 3, 2018. Therapy efficacy was evaluated based on the ulcer size and pain score before versus 7 days after either therapy. The paired t-test, chi-squared test, and independent t-test were utilized for statistical analyses. There was no significant difference in ulcer size or pain score between the HA and dexamethasone groups, on day 1 or day 7. Both treatments were tolerated well and no side effects were reported. No significant differences in body temperature, respiration rate, pulse, or systolic/diastolic blood pressure were observed between the start (day 1) and end of treatment (day 7), for either treatment. HA and dexamethasone showed similar efficacy in reducing ulcer size and pain scores, and were tolerated equally well in children with RAU. Future high-quality studies with larger numbers of patients are needed to confirm our findings.
  • Predictors of chest drainage of pneumothorax in neonates Research Article

    Tan, Ya-lan; Zhan, Yang; Geng, Jia; Chen, Wei; Guo, Wan-Liang

    Resumo em Inglês:

    This is a retrospective, single-center observational study to explore the predictors of chest drainage for neonatal pneumothorax. A total of 183 neonates (age ≤28 days) who presented to the Children's Hospital of Soochow University between January 1, 2015 and December 31, 2018 for pneumothorax or developed pneumothorax during a hospital stay were included. Demographic data, clinical presentation, and imaging characteristics of neonatal pneumothorax were collected and analyzed. We used univariate and multivariate logistic regression analyses to determine significant predictors of chest drainage of pneumothorax in neonates. Pneumothorax occurred within 24 h after birth in 131 (71.6%) cases, between 24 and 48 h after birth in 41 (22.4%) cases, and 48 h after birth in 11 (6.0%) cases. Univariate and multivariate logistic regression analyses revealed that lung collapse ≥1/3 on initial chest X-ray (OR 4.99, 95%CI 2.25-11.07), chest retractions (OR 8.12, 95%CI 2.88-22.89), cyanosis (OR 2.25, 95%CI 1.08-4.66), and frothing from mouth (OR 2.49, 95%CI 1.12-5.49) (P<0.05 for all) were significant predictors of the need for chest drainage due to pneumothorax. In conclusion, the thorough evaluation of the above predictive factors can guide treatment and improve patient outcome.
  • Estrogen attenuates TGF-β1-induced EMT in intrauterine adhesion by activating Wnt/β-catenin signaling pathway Research Article

    Cao, Jia; Liu, Dan; Zhao, Shiyun; Yuan, Liwei; Huang, Yani; Ma, Jingwen; Yang, Zhijuan; Shi, Bin; Wang, Libin; Wei, Jun

    Resumo em Inglês:

    Although estrogen has crucial functions for endometrium growth, the specific dose and underlying molecular mechanism in intrauterine adhesion (IUA) remain unclear. In this study, we aimed to investigate the effects of estrogen on epithelial-mesenchymal transition (EMT) in normal and fibrotic endometrium, and the role of estrogen and Wnt/β-catenin signaling in the formation of endometrial fibrosis. CCK-8 and immunofluorescence assay were performed to access the proliferation of different concentrations of estrogen on normal human endometrial epithelial cells (hEECs). qRT-PCR and western blot assay were utilized to explore the effect of estrogen on EMT in normal and fibrotic endometrium, and main components of Wnt/β-catenin signaling pathway in vitro. Hematoxylin and eosin and Masson staining were used to evaluate the effect of estrogen on endometrial morphology and fibrosis in vivo. Our results indicated that the proliferation of normal hEECs was inhibited by estrogen at a concentration of 30 nM accompanied by upregulation of mesenchymal markers and downregulation of epithelial markers. Interestingly, in the model of transforming growth factor β1 (TGF-β1)-induced endometrial fibrosis, the same concentration of estrogen inhibited the process of EMT, which might be partially mediated by regulation of the Wnt/β-catenin pathway. In addition, relatively high doses of estrogen efficiently increased the number of endometrial glands and reduced the area of fibrosis as determined by the reduction of EMT in IUA animal models. Taken together, our results demonstrated that an appropriate concentration of estrogen may prevent the occurrence and development of IUA by inhibiting the TGF-β1-induced EMT and activating the Wnt/β-catenin pathway.
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