Resumo em Inglês:

Oxidative stress plays an important role in the development of diabetic cardiomyopathy. In the present study, we determined whether the effect of astragalus polysaccharides (APS) on diabetic cardiomyopathy was associated with its impact on oxidative stress. Streptozotocin (STZ)-induced diabetic mice and heterozygous superoxide dismutase (SOD2+/-) knockout mice were administered APS. The hemodynamics, cardiac ultrastructure, and the apoptosis, necrosis and proliferation of cardiomyocytes were assessed to evaluate the effect of APS on diabetic and oxidative cardiomyopathy. Furthermore, H2O2 formation, oxidative stress/damage, and SOD activity in cardiomyocytes were evaluated to determine the effects of APS on cardiac oxidative stress. APS therapy improved hemodynamics and myocardial ultrastructure with reduced apoptosis/necrosis, and enhanced proliferation in cardiomyocytes from both STZ-induced diabetic mice and heterozygous SOD2+/- knockout mice. In addition, APS therapy reduced H2O2 formation and oxidative stress/damage, and enhanced SOD activity in both groups of mice. Our findings suggest that APS had benefits in diabetic cardiomyopathy, which may be partly associated with its impact on cardiac oxidative stress.

Resumo em Inglês:

The molecular mechanism of nasopharyngeal carcinoma (NPC) is poorly understood and effective therapeutic approaches are needed. This research aimed to excavate the attractor modules involved in the progression of NPC and provide further understanding of the underlying mechanism of NPC. Based on the gene expression data of NPC, two specific protein-protein interaction networks for NPC and control conditions were re-weighted using Pearson correlation coefficient. Then, a systematic tracking of candidate modules was conducted on the re-weighted networks via cliques algorithm, and a total of 19 and 38 modules were separately identified from NPC and control networks, respectively. Among them, 8 pairs of modules with similar gene composition were selected, and 2 attractor modules were identified via the attract method. Functional analysis indicated that these two attractor modules participate in one common bioprocess of cell division. Based on the strategy of integrating systemic module inference with the attract method, we successfully identified 2 attractor modules. These attractor modules might play important roles in the molecular pathogenesis of NPC via affecting the bioprocess of cell division in a conjunct way. Further research is needed to explore the correlations between cell division and NPC.

Resumo em Inglês:

Pseudobrickellia brasiliensis (Asteraceae) is a plant commonly known as arnica-do-campo and belongs to the native flora of the Brazilian Cerrado. The alcoholic extract of the plant has been used as an anti-inflammatory agent in folk medicine, but the biological mechanism of action has not been elucidated. The present study evaluated the composition of P. brasiliensis aqueous extract and its effects on pro-inflammatory cytokine production and lymphocyte proliferation. The extracts were prepared by sequential maceration of P. brasiliensis leaves in ethanol, ethyl acetate, and water. Extract cytotoxicity was evaluated by trypan blue exclusion assay, and apoptosis and necrosis were measured by staining with annexin V-FITC and propidium iodide. The ethanolic (ETA) and acetate (ACE) extracts showed cytotoxic effects. The aqueous extract (AQU) was not cytotoxic. Peripheral blood mononuclear cells stimulated with phorbol myristate acetate and ionomycin and treated with AQU (100 μg/mL) showed reduced interferon (IFN)-γ and tumor necrosis factor (TNF)-α expression. AQU also inhibited lymphocyte proliferative response after nonspecific stimulation with phytohemagglutinin. The aqueous extract was analyzed by liquid chromatography coupled with photodiode array detection and mass spectrometry. Quinic acid and its derivatives 5-caffeoylquinic acid and 3,5-dicaffeoylquinic acid, as well as the flavonoids luteolin and luteolin dihexoside, were detected. All these compounds are known to exhibit anti-inflammatory activity. Taken together, these findings demonstrate that P. brasiliensis aqueous extract can inhibit the pro-inflammatory cytokine production and proliferative response of lymphocytes. These effects may be related to the presence of chemical substances with anti-inflammatory actions previously reported in scientific literature.

Resumo em Inglês:

This study aimed to investigate possible asymmetries and relationships between performance of dominant and non-dominant upper limbs (UL) in patients with Duchenne and Becker muscular dystrophies (DMD/BMD), to compare UL performance of patients and healthy subjects and to investigate the relationship between timed performance of UL and age, motor function and muscle strength in DMD/BMD patients. Sixteen patients with DMD and 3 with BMD were evaluated with Jebsen-Taylor Test (timed performance), Vignos scale and Dimension 3 of Motor Function Measure (motor function), and Medical Research Council scale (muscle strength) on a single session. ANOVA showed no asymmetry between dominant and non-dominant UL, except in the writing subtest, in patients and in healthy controls. There were relationships between dominant and non-dominant UL performances. Correlations between timed performance, motor function and muscle strength were found, but age was not correlated with these variables. These findings may reduce the assessment time, prevent fatigue and provide more accurate clinical reasoning involving UL in DMD/BMD treatment.

Resumo em Inglês:

The aim of this study was to evaluate the feasibility of endoscopy to remove keratocystic odontogenic tumors (KCOTs) with virtual 3D mandibular images. Fifteen patients (mean age, 40.27±14.58 years) who underwent endoscopic mandibular KCOT enucleation between May 2009 and October 2009 were included. Virtual 3D mandibular reconstructions derived from computed tomography (CT) imaging were generated for all patients. Recurrence and pathological fracture were evaluated as the primary outcome variables at 1 and 12 months after operation. Secondary infection and inferior alveolar nerve injury were evaluated as the secondary outcome variables at 1 and 6 months after operation. None of the 15 patients exhibited signs of recurrence or pathological fracture after operation. During long-term follow-up, no symptoms of inferior alveolar nerve injury or secondary infection were observed and no signs of recurrence were found in any of the patients. Endoscopy helps surgeons to remove mandibular KCOTs with small incisions. Moreover, endoscopy can provide clear and magnified views and help to avoid damage to the inferior alveolar neurovascular bundle. Therefore, under the support of preoperative virtual 3D mandibular images, the application of endoscopy to remove the tumors should be considered to be a treatment option for KCOTs.

Resumo em Inglês:

As a mechanism compensating for obstructive coronary artery disease, coronary collateral circulation (CCC) has attracted cardiologists for a long time to explore its potential impact. In the present study, Chinese patients suffering from ≥95% coronary stenosis, as diagnosed by angiography, have been investigated for the correlation between CCC and lipoprotein(a) [Lp(a)] levels. A cohort of 654 patients was divided into four categories according to Rentrop grades 0, 1, 2, and 3. Lp(a) levels were divided into model 1, discretized with critical values of 33 and 66%, and model 2, discretized with a cutoff value of 30.0 mg/dL. Furthermore, we evaluated the correlation between CCC and serum Lp(a) levels. The four groups had significantly different Lp(a) levels (25.80±24.72, 18.99±17.83, 15.39±15.80, and 8.40±7.75 mg/dL; P<0.001). In model 1, concerning R0, the risk in the third Lp (a) tertile (OR=3.34, 95%CI=2.32-4.83) was greater than that in the first tertile. In model 2, concerning R0, the risk in Lp(a) >30.0 group (OR=6.77, 95%CI=4.44-10.4) was greater than that of Lp(a) <30.0 mg/dL. The worst condition of CCC can be predicted independently by Lp(a) levels. In addition to clinical usage, Lp(a) levels can also be utilized as biological markers.

Resumo em Inglês:

Sickle cell anemia (SCA) causes dysfunction of multiple organs, with pulmonary involvement as a major cause of mortality. Recently, there has been growing interest in the nitrogen single-breath washout (N2SBW) test, which is able to detect ventilation heterogeneity and small airway disease when the results of other pulmonary function tests (PFTs) are still normal. Thus, the objectives of the present study were to assess the heterogeneity in the ventilation distribution in adults with SCA and to determine the association between the ventilation distribution and the clinical, cardiovascular, and radiological findings. This cross-sectional study included 38 adults with SCA who underwent PFTs, echocardiography, computed tomography (CT), and 6-min walk test. To evaluate the ventilation heterogeneity, the patients were categorized according to the phase III slope of the N2SBW (SIIIN2). Compared with adults with lower SIIIN2 values, adults with higher SIIIN2 values showed lower hemoglobin levels (P=0.048), a history of acute chest syndrome (P=0.001), an elevated tricuspid regurgitation velocity (P=0.039), predominance of a reticular pattern in the CT (P=0.002), a shorter 6-min walking distance (6MWD) (P=0.002), and lower peripheral oxygen saturation (SpO2) after exercise (P=0.03). SIIIN2 values correlated significantly with hemoglobin (rs=-0.344; P=0.034), forced vital capacity (rs=-0.671; P<0.0001), diffusing capacity for carbon monoxide (rs=-0.376; P=0.019), 6MWD (rs=-0.554; P=0.0003), and SpO2 after exercise (P=0.040). Heterogeneity in the ventilation distribution is one of the most common pulmonary dysfunctions in adults with SCA. Moreover, relationships exist between ventilation heterogeneity, worsening of pulmonary structural damage, and reduced tolerance for exercise.

Resumo em Inglês:

This study aimed to investigate the function and mechanism of microRNA-143 (miR-143) in the occurrence and development of breast cancer (BC). A total of 30 BC tissues, 30 corresponding noncancerous tissues, and 10 normal control (NC) breast tissues were obtained to detect the levels of miR-143, extracellular signal-regulated kinase 5 (ERK5) and mitogen-activated protein 3 kinase 7 (MAP3K7) using RT-qPCR, western blotting or immunohistochemistry. The correlation of miR-143 with ERK5 or MAP3K7 was evaluated using Pearson correlation analysis. MCF-7 cells were transiently transfected with miR-143 mimic, miR-143 inhibitor, miR-143 mimic/inhibitor + si-ERK5, si-MAP3K7 or si-cyclin D1. Then, cell growth was evaluated by MTT assay and the expressions of phospho-ERK5 (p-ERK5), ERK5, p-MAP3K7, MAP3K7 and cyclin D1 were detected by western blotting. Results showed that, compared with noncancerous tissues or NC breast tissues, miR-143 level was decreased, while p-ERK5, ERK5, p-MAP3K7 and MAP3K7 expressions were increased in BC tissues (all P<0.01). The miR-143 level was negatively correlated with the mRNA level of ERK5 or MAP3K7 (r=-4.231 or r=-4.280, P<0.01). In addition, up-regulated miR-143 significantly decreased the expressions of p-ERK5, ERK5, p-MAP3K7, MAP3K7 and cyclin D1 (all P<0.01), as well as cell viability in MCF-7 cells (all P<0.05) while the effect of down-regulated miR-143 was the opposite. In conclusion, both ERK5 and MAP3K7 may be the target genes of miR-143. Increased expression of miR-143 can inhibit cell growth, which may be associated with ERK5 and MAP3K7 expressions in BC.

Resumo em Inglês:

Cancer stem cells reside in a distinct region within the tumor microenvironment that it is believed to play a fundamental role in regulating stemness, proliferation, survival, and metabolism of cancer cells. This study aimed to analyze the effect of extracellular alkalinization on metabolism and survival of human CD24-/CD44+ breast cancer stem cells (BCSCs). BCSCs were cultured in alkalinized DMEM-F12 and incubated at 37°C, 5% CO2, and 20% O2 for 30 min, 6, 24, and 48 h. After each incubation period, we analyzed the modulation of various mRNA expressions related to pH and cellular metabolic regulation using the qRT-PCR. Metabolic state was measured using colorimetric and fluorometric assays. To examine cell proliferation and apoptosis, we used trypan blue and annexin V/propidium iodide assay, respectively. This study demonstrated that alkalinization could stimulate extracellular carbonic anhydrase (CAe) activity, as well as CA9 and HIF1α expression. Under alkaline pH and HIF1α regulation, glucose consumption, extracellular lactate production, and LDH activity of BCSCs were upregulated while O2 consumption was downregulated. These metabolic shifts seemed to promote apoptosis and suppress the proliferation of BCSCs. To conclude, modulation of the extracellular environment through alkalinization could change the metabolic states of BCSCs, which in turn affect the cell survival.

Resumo em Inglês:

Both sorafenib and interleukin-27 (IL-27) are antineoplastic drugs. This study aimed to investigate the synergistic effect of these two drugs on bladder cancer cells. HTB-9 and T24 cells were stimulated with IL-27 (50 ng/mL), sorafenib (2 μM) or the synergistic action of these two drugs. The cells without treatment acted as control. Cell proliferation, apoptosis and invasion were measured by bromodeoxyuridine assay, flow cytometry and modified Boyden chamber, respectively. Simultaneously, both modified Boyden chamber and scratch assay were used to assess cell migration. Finally, the phosphorylation levels of key kinases in the Akt/mechanistic target of rapamycin (mTOR)/mitogen-activated protein kinase (MAPK) pathway, and expression levels of matrix metalloproteinase (MMP)-2 and MMP-9 were detected by western blot analysis. Stimulation with IL-27 or sorafenib repressed proliferation, migration and invasion but promoted apoptosis, and the effects were all enhanced by the combination of these two drugs in HTB-9 cells. The effect of the combined treatment on bladder cancer cells was verified in T24 cells. Additionally, the phosphorylation levels of AKT, mTOR and MAPK as well as the expression levels of MMP-2 and MMP-9 were all decreased by a single treatment of IL-27 or sorafenib, and further decreased by the combined treatment of these two drugs. The combination of IL-27 and sorafenib inhibited proliferation, migration and invasion and promoted apoptosis of bladder cancer cells compared with mono-drug treatment. Additionally, the AKT/mTOR/MAPK pathway might be implicated in the functional effects by down-regulations of MMP-2 and MMP-9.

Resumo em Inglês:

Ischemia/reperfusion injury is still a major cause of morbidity and mortality during liver surgery and transplantation. A variety of surgical and pharmacological therapeutic strategies have been investigated to minimize the effects of ischemia/reperfusion. The aim of our study was to analyze and compare preventive influences of ischemic preconditioning, adenosine and prostaglandin E1 in the experimental model of hepatic ischemia/reperfusion injury. Adult chinchilla rabbits were divided into four groups: 10 rabbits subjected to liver ischemic preconditioning (3-min period of inflow occlusion followed by a 5-min period of reperfusion) followed by 45 min of Pringle maneuver; 10 rabbits subjected to pre-treatment with intraportal injection of adenosine followed by 45 min of Pringle maneuver; 10 rabbits subjected to pre-treatment with intraportal injection of prostaglandin E1 followed by 45 min of Pringle maneuver; and control group of 10 rabbits subjected to 45 min of inflow liver ischemia without any preconditioning. On the second postoperative day, blood samples were obtained and biochemical parameters of liver function were measured and compared. Liver tissue samples were also obtained and histopathological changes were compared. Based on biochemical and histopathological parameters, it was demonstrated that ischemic preconditioning provided the best protection against hepatic ischemia/reperfusion injury. This was probably due to a wider range of mechanisms of action of this method oriented to reduce oxidative stress and inflammation, and restore liver microcirculation and hepatocyte energy compared to the examined pharmacological strategies.

Resumo em Inglês:

Asthma is a chronic allergic disease characterized by airway inflammation, airway hyper-responsiveness (AHR), and mucus hypersecretion. T-lymphocytes are involved in the pathogenesis of asthma, mediating airway inflammatory reactions by secreting cytokines. The phosphoinositide 3-kinase (PI3K) and Notch signaling pathways are associated with T cell signaling, proliferation, and differentiation, and are important in the progression of asthma. Thus, compounds that can modulate T cell proliferation and function may be of clinical value. Here, we assessed the effects of tangeretin, a plant-derived flavonoid, in experimental asthma. BALB/c mice at postnatal day (P) 12 were challenged with ovalbumin (OVA). Separate groups of mice (n=18/group) were administered tangeretin at 25 or 50 mg/kg body weight by oral gavage. Dexamethasone was used as a positive control. Tangeretin treatment reduced inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF) and also restored the normal histology of lung tissues. OVA-specific IgE levels in serum and BALF were reduced. AHR, as determined by airway resistance and lung compliance, was normalized. Flow cytometry analyses revealed a reduced Th17 cell population. Tangeretin reduced the levels of Th2 and Th17 cytokines and raised IFN-γ levels. PI3K signaling was inhibited. The expressions of the Notch 1 receptor and its ligands Jagged 1 and 2 were downregulated by tangeretin. Our findings support the possible use of tangeretin for treating allergic asthma.