Scielo RSS <![CDATA[Brazilian Journal of Medical and Biological Research]]> vol. 51 num. 6 lang. en <![CDATA[SciELO Logo]]> <![CDATA[Dietary intake and eating behavior in depot medroxyprogesterone acetate users: a systematic review]]> Because of weight gain, women often discontinue hormonal contraception, especially depot medroxyprogesterone acetate (DMPA). Our objective was to conduct a systematic review of studies describing dietary intake or eating behavior in DMPA users to understand whether the use of DMPA is associated with changes in dietary habits and behaviors leading to weight gain. We searched the PubMed, POPLINE, CENTRAL Cochrane, Web of Science, and EMBASE databases for reports published in English between 1980 and 2017 examining dietary intake or eating behavior in healthy women in reproductive age and adolescents using DMPA (150 mg/mL). Of the 749 publications screened, we excluded 742 due to duplicates (96), not addressing the key research question (638), not reporting dietary intake data (4), and not evaluating the relationship of body weight and dietary or eating behaviors (4). We identified seven relevant studies, including one randomized placebo-controlled trial, one non-randomized paired clinical trial, and five cohort studies. The randomized trial found no association and the other reports were inconsistent. Findings varied from no change in dietary intake or eating behavior with DMPA use to increased appetite in the first six months of DMPA use. Few studies report dietary intake and eating behavior in DMPA users and the available data are insufficient to conclude whether DMPA use is associated with changes in dietary habits or behavior leading to weight gain. <![CDATA[Exploration of gene functions for esophageal squamous cell carcinoma using network-based guilt by association principle]]> Gene networks have been broadly used to predict gene functions based on guilt by association (GBA) principle. Thus, in order to better understand the molecular mechanisms of esophageal squamous cell carcinoma (ESCC), our study was designed to use a network-based GBA method to identify the optimal gene functions for ESCC. To identify genomic bio-signatures for ESCC, microarray data of GSE20347 were first downloaded from a public functional genomics data repository of Gene Expression Omnibus database. Then, differentially expressed genes (DEGs) between ESCC patients and controls were identified using the LIMMA method. Afterwards, construction of differential co-expression network (DCN) was performed relying on DEGs, followed by gene ontology (GO) enrichment analysis based on a known confirmed database and DEGs. Eventually, the optimal gene functions were predicted using GBA algorithm based on the area under the curve (AUC) for each GO term. Overall, 43 DEGs and 67 GO terms were gained for subsequent analysis. GBA predictions demonstrated that 13 GO functions with AUC&gt;0.7 had a good classification ability. Significantly, 6 out of 13 GO terms yielded AUC&gt;0.8, which were determined as the optimal gene functions. Interestingly, there were two GO categories with AUC&gt;0.9, which included cell cycle checkpoint (AUC=0.91648), and mitotic sister chromatid segregation (AUC=0.91597). Our findings highlight the clinical implications of cell cycle checkpoint and mitotic sister chromatid segregation in ESCC progression and provide the molecular foundation for developing therapeutic targets. <![CDATA[Neonatal tobacco smoke reduces thermogenesis capacity in brown adipose tissue in adult rats]]> Maternal smoking is a risk factor for progeny obesity. We have previously shown, in a rat model of neonatal tobacco smoke exposure, a mild increase in food intake and a considerable increase in visceral adiposity in the adult offspring. Males also had secondary hyperthyroidism, while females had only higher T4. Since brown adipose tissue (BAT) hypofunction is related to obesity, here we tested the hypothesis that higher levels of thyroid hormones are not functional in BAT, suggesting a lower metabolic rate. We evaluated autonomic nerve activity in BAT and its function in adult rats that were exposed to tobacco smoke during lactation. At birth, litters were adjusted to 3 male and 3 female pups/litter. From postnatal day (PND) 3 to 21, Wistar lactating rats and their pups were divided into SE group, smoke-exposed in a cigarette smoking machine (4 times/day) and C group, exposed to filtered air. Offspring were sacrificed at PND180. Adult SE rats of both genders had lower interscapular BAT autonomic nervous system activity, with higher BAT mass but no change in morphology. BAT UCP1 and CPT1a protein levels were decreased in the SE groups of both genders. Male SE rats had lower β3-AR, TRα1, and TRβ1 expression while females showed lower PGC1α expression. BAT Dio2 mRNA and hypothalamic POMC and MC4R levels were similar between groups. Hypothalamic pAMPK level was higher in SE males and lower in SE females. Thus, neonatal cigarette smoke exposure induces lower BAT thermogenic capacity, which can be obesogenic at adulthood. <![CDATA[miR-27a protects human mitral valve interstitial cell from TNF-α-induced inflammatory injury via up-regulation of NELL-1]]> MicroRNAs (miRNAs) have been reported to be associated with heart valve disease, which can be caused by inflammation. This study aimed to investigate the functional impacts of miR-27a on TNF-α-induced inflammatory injury in human mitral valve interstitial cells (hMVICs). hMVICs were subjected to 40 ng/mL TNF-α for 48 h, before which the expressions of miR-27a and NELL-1 in hMVICs were altered by stable transfection. Trypan blue staining, BrdU incorporation assay, flow cytometry detection, ELISA, and western blot assay were performed to detect cell proliferation, apoptosis, and the release of proinflammatory cytokines. We found that miR-27a was lowly expressed in response to TNF-α exposure in hMVICs. Overexpression of miR-27a rescued hMVICs from TNF-α-induced inflammatory injury, as cell viability and BrdU incorporation were increased, apoptotic cell rate was decreased, Bcl-2 was up-regulated, Bax and cleaved caspase-3/9 were down-regulated, and the release of IL-1β, IL-6, and MMP-9 were reduced. NELL-1 was positively regulated by miR-27a, and NELL-1 up-regulation exhibited protective functions during TNF-α-induced cell damage. Furthermore, miR-27a blocked JNK and Wnt/β-catenin signaling pathways, and the blockage was abolished when NELL-1 was silenced. This study demonstrated that miR-27a overexpression protected hMVICs from TNF-α-induced cell damage, which might be via up-regulation of NELL-1 and thus modulation of JNK and Wnt/β-catenin signaling pathways. <![CDATA[Andrographolide protects mouse astrocytes against hypoxia injury by promoting autophagy and S100B expression]]> Andrographolide (ANDRO) has been studied for its immunomodulation, anti-inflammatory, and neuroprotection effects. Because brain hypoxia is the most common factor of secondary brain injury after traumatic brain injury, we studied the role and possible mechanism of ANDRO in this process using hypoxia-injured astrocytes. Mouse cortical astrocytes C8-D1A (astrocyte type I clone from C57/BL6 strains) were subjected to 3 and 21% of O2 for various times (0–12 h) to establish an astrocyte hypoxia injury model in vitro. After hypoxia and ANDRO administration, the changes in cell viability and apoptosis were assessed using CCK-8 and flow cytometry. Expression changes in apoptosis-related proteins, autophagy-related proteins, main factors of JNK pathway, ATG5, and S100B were determined by western blot. Hypoxia remarkably damaged C8-D1A cells evidenced by reduction of cell viability and induction of apoptosis. Hypoxia also induced autophagy and overproduction of S100B. ANDRO reduced cell apoptosis and promoted cell autophagy and S100B expression. After ANDRO administration, autophagy-related proteins, S-100B, JNK pathway proteins, and ATG5 were all upregulated, while autophagy-related proteins and s100b were downregulated when the jnk pathway was inhibited or ATG5 was knocked down. ANDRO conferred a survival advantage to hypoxia-injured astrocytes by reducing cell apoptosis and promoting autophagy and s100b expression. Furthermore, the promotion of autophagy and s100b expression by ANDRO was via activation of jnk pathway and regulation of ATG5. <![CDATA[Influence of expiratory positive airway pressure on cardiac autonomic modulation at rest and in submaximal exercise in COPD patients]]> The aim of this study was to evaluate the effect of expiratory positive airway pressure (EPAP) on heart rate variability (HRV) indices at rest and during 6-min walk test (6MWT) in chronic obstructive pulmonary disease (COPD) patients. Fifteen moderate to severe COPD patients were randomized and evaluated with and without (Non-EPAP) a 5 cmH2O EPAP device. Respiratory rate (RR) was collected at rest (5 min), during the 6MWT (5 min), and at recovery (5 min). Indices of HRV were computed in the time domain, in the frequency domain, and nonlinear analysis. For EPAP and Non-EPAP during the 6MWT, we found an increased mean heart rate (HR) (P=0.001; P=0.001) while mean RR (P=0.001; P=0.015) and RR tri index decreased (P=0.006; P=0.028). Peripheral oxygen saturation (P=0.019) increased at rest only in the EPAP group. In EPAP, correlations were found between forced expiratory volume in 1 s (FEV1) and low frequency (LF) sympathetic tonus (P=0.05; r=-0.49), FEV1 and high frequency (HF) parasympathetic tonus at rest (P=0.05; r=0.49), lactate at rest and LF during the 6MWT (P=0.02; r=-0.57), and lactate at rest and HF during 6MWT (P=0.02; r=0.56). Through a linear regression model, we found that lactate at rest explained 27% of the alterations of LF during 6MWT. The use of 5 cmH2O EPAP improved autonomic cardiac modulation and its complexity at rest in COPD patients. Although it did not influence the performance of the 6MWT, the EPAP device caused alterations in resting lactate concentration with an effect on sympatho-vagal control during the test. <![CDATA[Beetle (<em>Ulomoides dermestoides</em>) fat improves diabetes: effect on liver and pancreatic architecture and on PPARγ expression]]> Ulomoides dermestoides is a beetle traditionally consumed to treat diabetes. In this study, we performed a composition analysis of U. dermestoides to obtain the principal fractions, which were used to assess the effect on glycemia, liver and pancreatic architecture, and PPARγ and GLUT4 expression. Normal mice and alloxan-induced diabetic mice were administered fractions of chitin, protein or fat, and the acute hypoglycemic effect was evaluated. A subacute study involving daily administration of these fractions to diabetic mice was also performed over 30 days, after which the liver and pancreas were processed by conventional histological techniques and stained with hematoxylin and eosin to evaluate morphological changes. The most active fraction, the fat fraction, was analyzed by gas chromatography-mass spectrometry (GC-MS), and PPARγ and GLUT4 mRNA expressions were determined in 3T3-L1 adipocytes. The protein and fat fractions exhibited hypoglycemic effects in the acute as well as in the 30-day study. Only the fat fraction led to elevated insulin levels and reduced glycemia, as well as lower intake of water and food. In the liver, we observed recovery of close hepatic cords in the central lobule vein following treatment with the fat fraction, while in the pancreas there was an increased density and percentage of islets and number of cells per islet, suggesting cellular regeneration. The GC-MS analysis of fat revealed three fatty acids as the major components. Finally, increased expression of PPARγ and GLUT4 was observed in 3T3-L1 adipocytes, indicating an antidiabetic effect. <![CDATA[Protective effect of yerba mate intake on the cardiovascular system: a <em>post hoc</em> analysis study in postmenopausal women]]> The prevalence of cardiovascular and metabolic diseases is increased in postmenopausal women, which contributes to the burden of illnesses in this period of life. Yerba mate (Ilex paraguariensis) is a native bush from Southern South America. Its leaves are rich in phenolic components, which may have antioxidant, vasodilating, hypocholesterolemic, and hypoglycemic proprieties. This post hoc analysis of the case-control study nested in the Obesity and Bone Fracture Cohort evaluated the consumption of yerba mate and the prevalence of hypertension, dyslipidemia, and coronary diseases in postmenopausal women. Ninety-five postmenopausal women were included in this analysis. A questionnaire was applied to evaluate the risk factors and diagnosis of cardiovascular diseases and consumption of yerba mate infusion. Student's t-test and chi-square test were used to assess significant differences between groups. The group that consumed more than 1 L/day of mate infusion had significantly fewer diagnoses of coronary disease, dyslipidemia, and hypertension (P&lt;0.049, P&lt;0.048, and P&lt;0.016, respectively). Furthermore, the serum levels of glucose were lower in the group with a higher consumption of yerba mate infusion (P&lt;0.013). The serum levels of total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides were similar between the groups. This pragmatic study points out the benefits of yerba mate consumption for the cardiovascular and metabolic systems. The ingestion of more than 1 L/day of mate infusion was associated with fewer self-reported cardiovascular diseases and lower serum levels of glucose. Longitudinal studies are needed to evaluate the association between yerba mate infusion and reduction of cardiovascular diseases in postmenopausal women. <![CDATA[Quality of life on hemodialysis and inflammation: a descriptive analysis]]> Chronic kidney disease (CKD) is highly prevalent worldwide. Patients with CKD on hemodialysis are more likely to present behavioral changes and worse quality of life as a result of their routine and complications. They also have higher levels of cytokines. The aim of this study is to assess the relationship between the inflammatory profile and quality of life measured by KDOQL-SF36 in hemodialysis outpatients. Patients older than 21 years of age and on routine hemodialysis for at least 6 months with treatment on a regular weekly basis were included and their anthropometric parameters and serum inflammatory markers were evaluated. Thirty patients consented to participate. Homocysteine (Hcy) levels were correlated with worse glomerular filtration rate (GFR; P=0.003) and creatinine (P=0.002). IL-6 was not correlated with worse nutritional status taking into account body mass index (BMI; kg/m2; P=0.83). On the other hand, TNF-alpha was positively correlated with albumin (P=0.008), nutritional status by BMI (P=0.04), and nutritional status by arm circumference area (P=0.04). IL-6 was correlated with activity limitation (P=0.02) and Hcy with work status (P=0.04). Hcy was correlated with nutritional status and inflammatory markers. In this population, the majority of the sections in KDOQL-SF36 were not correlated with cytokines levels. <![CDATA[Long non-coding RNA-ROR aggravates myocardial ischemia/reperfusion injury]]> Long non-coding RNAs (lncRNAs) play an important role in the pathogenesis of cardiovascular diseases, especially in myocardial infarction and ischemia/reperfusion (I/R). However, the underlying molecular mechanism remains unclear. In this study, we determined the role and the possible underlying molecular mechanism of lncRNA-ROR in myocardial I/R injury. H9c2 cells and human cardiomyocytes (HCM) were subjected to either hypoxia/reoxygenation (H/R), I/R or normal conditions (normoxia). The expression levels of lncRNA-ROR were detected in serum of myocardial I/R injury patients, H9c2 cells, and HCM by qRT-PCR. Then, levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) were measured by kits. Cell viability, apoptosis, apoptosis-associated factors, and p38/MAPK pathway were examined by MTT, flow cytometry, and western blot assays. Furthermore, reactive oxygen species (ROS) production was determined by H2DCF-DA and MitoSOX Red probes with flow cytometry. NADPH oxidase activity and NOX2 protein levels were measured by lucigenin chemiluminescence and western blot. Results showed that lncRNA-ROR expression was increased in I/R patients and in H/R treatment of H9c2 cells and HCM. Moreover, lncRNA-ROR significantly promoted H/R-induced myocardial injury via stimulating release of LDH, MDA, SOD, and GSH-PX. Furthermore, lncRNA-ROR decreased cell viability, increased apoptosis, and regulated expression of apoptosis-associated factors. Additionally, lncRNA-ROR increased phosphorylation of p38 and ERK1/2 expression and inhibition of p38/MAPK, and rescued lncRNA-ROR-induced cell injury in H9c2 cells and HCM. ROS production, NADPH oxidase activity, and NOX2 protein levels were promoted by lncRNA-ROR. These data suggested that lncRNA-ROR acted as a therapeutic agent for the treatment of myocardial I/R injury. <![CDATA[TNF-α inhibits SCF, ghrelin, and substance P expressions through the NF-κB pathway activation in interstitial cells of Cajal]]> Ulcerative colitis is a chronic inflammatory disease of the colon where intestinal motility is disturbed. Interstitial cells of Cajal (ICC) are required to maintain normal intestinal motility. In the present study, we assessed the effect of tumor necrosis factor-alpha (TNF-α) on viability and apoptosis of ICC, as well as on the expression of stem cell factor (SCF), ghrelin, and substance P. ICC were derived from the small intestines of Swiss albino mice. Cell viability and apoptosis were measured using CCK-8 assay and flow cytometry, respectively. ELISA was used to measure the concentrations of IL-1β, IL-6, ghrelin, substance P, and endothelin-1. Quantitative RT-PCR was used to measure the expression of SCF. Western blotting was used to measure the expression of apoptosis-related proteins, interleukins, SCF, and NF-κB signaling pathway proteins. TNF-α induced inflammatory injury in ICC by decreasing cell viability and increasing apoptosis and levels of IL-1β and IL-6. TNF-α decreased the levels of SCF, ghrelin, and substance P, but had no effect on endothelin-1. TNF-α down-regulated expressions of SCF, ghrelin, and substance P by activating the NF-κB pathway in ICC. In conclusion, TNF-α down-regulated the expressions of SCF, ghrelin, and substance P via the activation of the NF-κB pathway in ICC. <![CDATA[LncRNA HULC mediates radioresistance via autophagy in prostate cancer cells]]> Prostate cancer (PCa) is the second leading cause of cancer death in men. Irradiation is one of the available options for treatment of PCa, however, approximately 10–45% of PCa are resistant to irradiation. We aimed to explore the role of long non-coding RNA highly upregulated in liver cancer (HULC) in the sensitivity of PCa cells to irradiation. Survival rate, cell apoptosis, cycle, expressions of related proteins, and caspase-3 activity were assessed to explore the effects of HULC on sensitivity of PCa cells to irradiation. Expression of HULC in DU-145, PC3, LNCaP, and RWPE-1 cells was determined and the influence of HULC on DU-145 cells was explored. Then, PC3 cells aberrantly expressing HULC were implanted into NOD-SCID mice for tumor xenograft study. Changes of autophagy after aberrant expression of HULC in vivo and in vitro were tested. Furthermore, the interacted protein of HULC and involved signaling pathway were investigated. In PC3 and LNCaP cells under irradiation, survival rate and cell cycle were decreased and apoptosis was increased by HULC knockdown. HULC knockdown arrested PC3 cells at G0/G1 phase. DU-145 was sensitive to irradiation, and resistance to irradiation of DU-145 cells was enhanced by HULC overexpression. Moreover, HULC knockdown enhanced the sensitivity of PC3 xenografts to irradiation. HULC knockdown promoted autophagy through interaction with Beclin-1 and inhibition of mTOR, resulting in increased apoptosis. HULC knockdown improved sensitivity of PCa cells to irradiation both in vivo and in vitro. HULC suppressed Beclin-1 phosphorylation, thereby reduced autophagy, involving the mTOR pathway.