Accessibility / Report Error
Brazilian Journal of Medical and Biological Research, Volume: 53, Issue: 7, Published: 2020
  • Heart failure with preserved ejection fraction: an update on pathophysiology, diagnosis, treatment, and prognosis Review

    Ma, Chao; Luo, Huan; Fan, Lei; Liu, Xiaoyan; Gao, Chengshan

    Abstract in English:

    Heart failure (HF) with preserved ejection fraction (HFpEF) is a clinical syndrome in which patients have symptoms and signs of HF with normal or near-normal left ventricular ejection fraction (LVEF ≥50%). Roughly half of all patients with HF worldwide have an LVEF ≥50% and nearly half have an LVEF <50%. Thanks to the increased scientific attention about the condition and improved characterization and diagnostic tools, the incidence of HF with reduced ejection fraction (HFrEF) dropped while that of HFpEF has increased by 45%. HFpEF has no single guideline for diagnosis or treatment, the patient population is heterogeneously and inconsistently described, and longitudinal studies are lacking. To better understand and overcome the disease, in this review, we updated the latest knowledge of HFpEF pathophysiology, introduced the existing promising diagnostic methods and treatments, and summarized its prognosis by reviewing the most recent cohort studies.
  • Reaching task performance is associated to neuromuscular junction adaptations in rats with induced diabetes mellitus Research Article

    Estrada-Bonilla, Y.C.; Castro, P.A.T.S.; Luna, G.L.F.; Souza, A.B.A.; Santos, G.S.; Salvini, T.F.; Leal, A.M.O.; Russo, T.L.

    Abstract in English:

    Upper limb performance is affected by diabetes mellitus (DM). Neuromuscular junction (NMJ) is a key structure to understand the relationship between performance and morphology in DM. The aim of the study was to analyze NMJ plasticity due to DM in an animal model and its relationship with the function of forelimbs in rats. Twelve Wistar rats were divided into control (C) and DM groups. Animals were trained to perform a grasping task, following procedures of habituation, shaping, and reaching task. DM was induced using streptozotocin. Forelimb neuromuscular performance for dexterity was evaluated one day before DM induction and five weeks following induction. After that, biceps, triceps, and finger flexors and extensors were removed. Connective tissue and muscle fiber cross-sectional area (CSA) were measured. NMJ was assessed by its morphometric characteristics (area, perimeter, and maximum diameter), using ImageJ software. Motor performance analyses were made using single pellet retrieval task performance test. Student’s t-test was used for comparisons between groups. A significant decrease in all NMJ morphometric parameters was observed in the DM group compared with the C group. Results showed that DM generated NMJ retraction in muscles involved in a reaching task. These alterations are related to signs of muscular atrophy and to poor reaching task performance. In conclusion, induced DM caused NMJ retraction and muscular atrophy in muscles involved in reaching task performance. Induced DM caused significantly lower motor performance, especially in the final moments of evaluation, when DM compromised the tropism of the muscular tissue.
  • MicroRNA-424-5p inhibits the proliferation, migration, and invasion of nasopharyngeal carcinoma cells by decreasing AKT3 expression Research Article

    Zhao, Chong; Zhao, Feng; Chen, Huiying; Liu, Yuehua; Su, Jiping

    Abstract in English:

    This study examined the expression and potential mechanism of microRNA (miRNA)-424-5p in nasopharyngeal carcinoma (NPC). NPC tissues were collected from 40 patients who were enrolled in the study, and skin samples were collected from 26 healthy subjects during plastic surgery as controls. We performed various in vitro assays using miR-424-5p to examine its function in primary NPC-1 cells. Bioinformatics was employed to analyze potential target genes and signaling pathways of miR-424-5p. We found that miR-424-5p expression in NPC tissues is downregulated and negatively correlated with lymph node metastasis and clinical staging. Expression of miR-424-5p in NPC cells was also downregulated, and transfection with miR-424-5p mimics inhibited proliferation, migration, and invasion of NPC-1 cells. Bioinformatics identified the AKT3 gene as a potential target of miR-424-5p and dual luciferase assays confirmed this finding. Upregulation of AKT3 expression rescued the inhibitory effect of miR-424-5p on the proliferation, migration, and invasion. Our results suggest that miR-424-5p inhibited the proliferation, migration, and invasion of NPC cells by decreasing AKT3 expression.
  • Knocking down LSD1 inhibits the stemness features of colorectal cancer stem cells Research Article

    Chen, J.; Zhao, Jianyong; Ding, J.; Wang, Ziwei; Du, Jiyi; Wu, Chenchang

    Abstract in English:

    As a top leading cause of cancer death in many countries, colorectal cancer (CRC) has drawn increasing attention to the study of the pathological mechanism. According to the “cancer stem cell hypothesis”, malignancies originate from a small fraction of cancer cells that show self-renewal properties to initiate and sustain tumor growth and tumor metastasis. Therefore, these cancer stem cells (CSC) probably play important roles in tumor recurrence, metastasis, and drug resistance. Previous research reported that lysine-specific histone demethylase 1 (LSD1) maintains cancer stemness through up-regulating stemness markers SOX2 and OCT4. CD133 is believed to be the most robust surface marker for CRC stem cells, however the regulatory effect of LSD1 on stemness of CD133+ CRC has never been reported. In this study, our objectives included: 1) to isolate pure CD133+ and CD133− cells from SW620 cell line; 2) to investigate the effect of LSD1 on the characteristics of CD133+ stem cancer cells by knocking down the target gene. Results suggested that the SW620 cell line had both CD133+ and CD133− subsets. The CD133+ subset exhibited more CSC-like characteristics compared with the CD133− subset with higher viability, colony formation rate, migration and invasion rate, resistance to anti-cancer drugs, and apoptosis in vitro. The CD133+ also induced faster tumor formation and larger tumors in vivo. In the LSD1-knockdown CD133+ cells, the CSC-like characteristics had been all weakened. We conclude that LSD1 was important for CSCs to maintain their “stemness” features, which could be a potential therapeutic target of CRC.
  • Ophiopogonin D of Ophiopogon japonicus ameliorates renal function by suppressing oxidative stress and inflammatory response in streptozotocin-induced diabetic nephropathy rats Research Article

    Qiao, Yanhong; Jiao, Haiyan; Wang, Feng; Niu, Huimin

    Abstract in English:

    Ophiopogonin D (OP-D) is the principal pharmacologically active ingredient from Ophiopogon japonicas, which has been demonstrated to have numerous pharmacological activities. However, its protective effect against renal damage in streptozotocin (STZ)-induced diabetic nephropathy (DN) rats remains unclear. The present study was performed to investigate the protective effect of OP-D in the STZ-induced DN rat model. DN rats showed renal dysfunction, as evidenced by decreased serum albumin and creatinine clearance, along with increases in serum creatinine, blood urea nitrogen, TGF-β1, and kidney hypertrophy, and these were reversed by OP-D. In addition, STZ induced oxidative damage and inflammatory response in diabetic kidney tissue. These abnormalities were reversed by OP-D treatment. The findings obtained in the present study indicated that OP-D might possess the potential to be a therapeutic agent against DN via inhibiting renal inflammation and oxidative stress.
  • Relationship between PI3K/mTOR/RhoA pathway-regulated cytoskeletal rearrangements and phagocytic capacity of macrophages Research Article

    Bao, H.R.; Chen, J.L.; Li, F.; Zeng, X.L.; Liu, X.J.

    Abstract in English:

    The objective of this study was to investigate the relationship between PI3K/mTOR/RhoA signaling regulated cytoskeletal rearrangements and phagocytic capacity of macrophages. RAW264.7 macrophages were divided into four groups; blank control, negative control, PI3K-RNAi, and mTOR-RNAi. The cytoskeletal changes in the macrophages were observed. Furthermore, the phagocytic capacity of macrophages against Escherichia coli is reported as mean fluorescence intensity (MFI) and percent phagocytosis. Transfection yielded 82.1 and 81.5% gene-silencing efficiencies against PI3K and mTOR, respectively. The PI3K-RNAi group had lower mRNA and protein expression levels of PI3K, mTOR, and RhoA than the blank and negative control groups (Р<0.01). The mTOR-RNAi group had lower mRNA and protein levels of mTOR and RhoA than the blank and the negative control groups (Р<0.01). Macrophages in the PI3K-RNAi group exhibited stiff and inflexible morphology with short, disorganized filopodia and reduced number of stress fibers. Macrophages in the mTOR-RNAi group displayed pronounced cellular deformations with long, dense filopodia and an increased number of stress fibers. The PI3K-RNAi group exhibited lower MFI and percent phagocytosis than blank and negative control groups, whereas the mTOR-RNAi group displayed higher MFI and percent phagocytosis than the blank and negative controls (Р<0.01). Before and after transfection, the mRNA and protein levels of PI3K were both positively correlated with mTOR and RhoA (Р<0.05), but the mRNA and protein levels of mTOR were negatively correlated with those of RhoA (Р<0.05). Changes in the phagocytic capacity of macrophages were associated with cytoskeletal rearrangements and were regulated by the PI3K/mTOR/RhoA signaling pathway.
  • Detoxification effects of long-chain versus a mixture of medium- and long-chain triglyceride-based fat emulsion on propafenone poisoning Research Article

    An, Xusheng; Mei, Yong; Sun, Hao; Zhang, Jinsong

    Abstract in English:

    In the present study, we aimed to compare the detoxifying effects of two fat emulsions containing either long-chain triglyceride or a mixture of medium-chain and long-chain triglycerides in the propafenone-poisoned rat model. Rats were randomly divided into 3 groups according to the fat emulsions used: long-chain triglyceride-based fat emulsion (LL) group; medium-chain and long-chain triglyceride-based fat emulsion (ML) group; normal saline (NS) group. Propafenone was continuously pumped (velocity=70 mg/kg per h) until the mean blood pressure dropped to 50% of basal level. Then, LL/ML fat emulsions or NS was intravenously infused instantly with a loading-dose (1.5 mL/kg) and a maintenance dose (0.25 mL/kg per min) for 1 h. Subsequently, the propafenone was added to plasma (3.5 μg/mL) in vitro, mixed with three doses of LL or ML (1, 2, or 4%). Finally, after centrifugation, the concentration of propafenone was measured. Rats treated with LL exhibited accelerated recovery, characterized by higher blood pressure and heart rate. Rats in both the LL and ML groups demonstrated decreased propafenone in plasma (time-points: 15, 25, and 60 min). However, rats that received LL showed lower propafenone in myocardial tissue at the end of detoxification treatment. Rats in the ML group had the lowest value of pH, the minimum content of HCO3-, and the highest production of lactic acid at the end. In the in vitro experiments, propafenone decreased more dramatically in the LL group compared to the ML group. Long-chain triglyceride fat emulsion had a better effect on treating propafenone poisoning in rats.
  • lncRNA PCGEM1 strengthens anti-inflammatory and lung protective effects of montelukast sodium in children with cough-variant asthma Research Article

    Xu, Zhenxing; Meng, Lingling; Xie, Yuejuan; Guo, Wei

    Abstract in English:

    Montelukast sodium is an effective and well-tolerated anti-asthmatic drug. Long non-coding RNAs (lncRNAs) are involved in the treatment of asthma. Therefore, this study aimed to investigate the effect of montelukast sodium on children with cough-variant asthma (CVA) and the role of lncRNA prostate cancer gene expression marker 1 (PCGEM1) in drug efficacy. The efficacy of montelukast sodium was evaluated by assessing the release of inflammatory factors and pulmonary function in CVA children after a 3-month treatment. An ovalbumin (OVA)-sensitized mouse model was developed to simulate asthmatic conditions. PCGEM1 expression in clinical peripheral blood samples and lung tissues of asthmatic mice was determined. Asthmatic mice experienced nasal inhalation of PCGEM1 overexpression with simultaneous montelukast sodium to investigate the roles of PCGEM1 in asthma treatment. The NF-κB axis after PCGEM1 overexpression was detected to explore the underling mechanisms. Consequently, montelukast sodium contributed to reduced levels of pro-inflammatory factors and improved pulmonary function in CVA children. PCGEM1 was poorly expressed in OVA-sensitized asthmatic mice and highly expressed in CVA children with response to the treatment. PCGEM1 overexpression enhanced the anti-inflammatory effects and promoted effects on pulmonary function of montelukast sodium in CVA children and OVA-sensitized asthmatic mice. Furthermore, PCGEM1 inhibited the activation of the NF-κB axis. This study demonstrated the anti-inflammatory and lung-protective effects of montelukast sodium on CVA, which was strengthened by overexpression of PCGEM1. Findings in this study highlighted a potential anti-asthmatic target of montelukast sodium.
  • Development of a three-channel automatic climbing training system for rat rehabilitation after ischemic stroke Research Article

    Chen, Chi-Chun; Chang, Ching-Ping

    Abstract in English:

    This paper reports the development of a three-channel automatic speed-matching climbing training system that could train three rats at the same time for rehabilitation after an ischemic stroke. An infrared (IR) remote sensor was installed at the end of each channel to monitor the real-time position of a climbing rat. This research was carried out in five stages: i) system design; ii) hardware circuit; iii) running speed control; iv) functional testing; and v) verification using an animal model of cerebral stroke. The rehabilitated group significantly outperformed the middle cerebral artery occlusion (MCAo) sedentary group in the rota-rod and inclined plate tests 21 days after a stroke. The rehabilitated group also had a cerebral infarction volume of 28.34±19.4%, far below 56.81±18.12% of the MCAo group 28 days after the stroke, validating the effectiveness of this training platform for stroke rehabilitation. The running speed of the climbing rehabilitation training platform was designed to adapt to the physical conditions of subjects, and overtraining injuries can be completely prevented accordingly.
  • Erratum for: “Puerarin inhibits hepatocellular carcinoma invasion and metastasis through miR-21-mediated PTEN/AKT signaling to suppress the epithelial-mesenchymal transition” [Braz J Med Biol Res (2020) 53(4): e8882] Erratum

Associação Brasileira de Divulgação Científica Av. Bandeirantes, 3900, 14049-900 Ribeirão Preto SP Brazil, Tel. / Fax: +55 16 3315-9120 - Ribeirão Preto - SP - Brazil
E-mail: bjournal@terra.com.br