Resumo em Inglês:

The neutrophil is an important cell in host defense against infections, acting as the first line of microorganism control. However, this cell exhibits dysregulated activity in sepsis and may contribute to the pathogenesis of the disease. This systematic review aimed to highlight the major scientific findings regarding neutrophil activity in sepsis reported in clinical and experimental research published in the last 10 years. The search was conducted in the Virtual Health Library of PAHO-WHO (BVS) and PubMed databases, and articles published between January 2007 and May 2017 in Portuguese, English, and Spanish were eligible. Article selection was carried out independently by two reviewers (CB and IB). A total of 233 articles were found, of which 87 were identified on PubMed and 146 on BVS. Eighty-two articles were duplicates. Of the remaining 151 articles, 19 met the inclusion criteria after title, abstract, and full-text analysis. Overall, research in clinical samples and animal models of sepsis showed reduced capacity of neutrophils to migrate and delayed apoptosis, but there was no consensus on the phagocytic activity of neutrophils in sepsis. Molecules, such as pentraxin 3 (PTX3), have been analyzed as potential diagnostic markers in sepsis but the diversity of soluble molecules detected in blood samples of sepsis patients did not enable further understanding of the correlation of these circulating molecules with neutrophil activity during sepsis. Optimal understanding of the function of neutrophils in sepsis remains a challenge that, if overcome, would eventually allow targeted therapeutic interventions in patients affected by this severe syndrome.

Resumo em Inglês:

Obesity affects the respiratory system through various mechanisms, including systemic inflammation and direct mechanical hindrance due to fat deposition in the chest and abdomen. In addition, changes in the neural control of respiration and increases in thoracic blood volume can promote abnormalities in lung function. Thus, determining relationships between the distance covered in the 6-min walk test (6MWT) and demographic and lung function variables may help us better understand the mechanisms involved in reduced functional exercise capacity in obesity. To explore the determinants of the 6-min walking distance (6MWD) and evaluate the influence of lung function on the distance covered, 263 obese Brazilian women performed the 6MWT and underwent spirometry and respiratory muscle strength measurement. The mean age was 41.8±11.1 years. The mean body mass index (BMI) was 45±8 kg/m2. The 6MWD showed correlations with height (r=0.319), age (r=-0.281), weight (r=-0.370), BMI (r=-0.561), forced vital capacity (FVC, r=0.443), expiratory peak flow (r=0.278), maximal inspiratory pressure (MIP, r=0.326), and maximal expiratory pressure (r=0.259), all with P<0.0001. In the stepwise forward regression analysis, BMI, FVC, age, and MIP were the independent predictive variables for 6MWD, explaining 41% of its variability. The reference equation including lung function was as follows: 6MWD (m) = 513.6 - (4.439 × BMIkg/m2) + (1.136 × FVC%predicted) - (1.048 × ageyrs) + (0.544 × MIP%predicted). Thus, the inclusion of lung function in a reference equation for 6MWD contributes to a better prediction of the distance covered in this population.

Resumo em Inglês:

We aimed to investigate the association of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (lnc-MALAT1) with acute ischemic stroke (AIS), and its association with disease severity, inflammation, and recurrence-free survival (RFS) in AIS patients. One hundred and twenty AIS patients and 120 controls were recruited. Venous blood samples from AIS patients (within 24 h after symptoms onset) and controls (at entry to study) were collected to detect plasma lnc-MALAT1 expression by real-time quantitative polymerase chain reaction. AIS severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) score. Plasma concentrations of inflammation factors (including C-reactive protein (CRP), tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-8, IL-10, IL-17, and IL-22) were measured and RFS was calculated. lnc-MALAT1 expression was decreased in AIS patients compared to controls, and it had a close correlation with AIS (AUC=0.791, 95% CI: 0.735-0.846). For disease condition, lnc-MALAT1 expression negatively correlated with NIHSS score and pro-inflammatory factor expression (including CRP, TNF-α, IL-6, IL-8, and IL-22), while it positively correlated with anti-inflammatory factor IL-10 expression. Furthermore, lnc-MALAT1 expression was elevated in AIS patients with diabetes. For prognosis, no statistical correlation of lnc-MALAT1 expression with RFS was found, while a trend for longer RFS was observed in patients with lnc-MALAT1 high expression compared to those with lnc-MALAT1 low expression.

Resumo em Inglês:

Preeclampsia (PE) is a complex pregnancy syndrome. Convincing evidence indicates that long non-coding RNAs (lncRNAs) are involved in the pathogenesis of PE. This research mainly investigated the mechanism of family with sequence similarity 99 member A (FAM99A) in PE. The expressions of FAM99A, miR-134-5p, and YAP1 were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell apoptosis, migration, and invasion were detected by flow cytometry or transwell assay. The interaction between miR-134-5p and FAM99A or YAP1 was confirmed by dual-luciferase reporter assay. The protein expression of YAP1 was determined by western blot assay. FAM99A and YAP1 were significantly up-regulated, and miR-134-5p was significantly down-regulated in PE tissues (n=30). miR-134-5p was verified as a candidate of FAM99A and YAP1. FAM99A promoted cell metastasis, but reduced apoptosis in HTR8/SVneo cells by regulating miR-134-5p. miR-134-5p down-regulated YAP1 expression to suppress cell metastasis, while it induced apoptosis in HTR8/SVneo cells. FAM99A positively modulated YAP1 expression by sponging miR-134-5p. FAM99A modulated YAP1 to accelerate cell migration and invasion, and inhibited cell apoptosis in PE cells by sponging miR-134-5p. The novel regulatory network may shed light on the pathogenesis of PE.

Resumo em Inglês:

Acne is a kind of common, chronic skin condition caused by the inflammation of the sebaceous glands in hair follicles. Recent studies have demonstrated that baicalin (BA) possesses potential anti-inflammatory properties. In this study, we evaluated the anti-inflammatory activity of BA in vitro and in vivo. Heat-killed Propionibacterium acnes-induced THP-1 cells and live P. acnes-injected male Sprague Dawley rats were used for establishing the acne model. The rate of ear swelling was calculated, and the severity was determined by hematoxylin and eosin staining. The production of cytokines [interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF-α)] in the cell supernatant and ear tissue homogenates was measured by ELISA. Protein levels of JNK, ERK, P38, IκBα, P65, Nod-like receptor pyrin domain-containing 3 (NLRP3), pro-caspase-1, and IL-1β in THP-1 cells and ear tissues were detected by western blotting. NLRP3 and IL-1β were detected by immunohistochemistry, and the NLRP3, IL-1β and pro-caspase-1 mRNAs were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The results showed that BA decreased the expression of pro-inflammatory cytokines in vitro and in vivo. Moreover, BA down-regulated the phosphorylation of JNK, ERK1/2, and κBα and inhibited the nuclear translocation of p65. Furthermore, BA inhibited the activation of NLRP3 inflammasome, at both the gene and protein levels. Taken together, the results demonstrated that BA might exert its anti-inflammatory activity by inhibiting NF-κB/MAPK signaling pathways and consequently suppressing the activation of the NLRP3 inflammasome both in vivo and in vitro.

Resumo em Inglês:

LINC00355 has been reported aberrantly over-expressed and associated with poor prognosis in various types of cancer. However, reports regarding the effect of LINC00355 on lung squamous cell carcinoma (SCC) are rare. This study aimed to explore the function of LINC00355 in the development and progression of lung SCC and reveal the underlying mechanism. The expression and subcellular location of LINC00355 were determined by qRT-PCR and RNA-FISH, respectively. The lung SCC cell growth was analyzed by CCK-8 assay, transwell invasion, wound healing, colony formation, and flow cytometry assays. Reactive oxygen species level was evaluated by DCFH-DA probes. Bioinformatics online websites, luciferase reporter assay, RNA binding protein immunoprecipitation (RIP), and RNA pull-down assays were utilized to investigate the interaction among LINC00355, miR-466, and Ly-1 antibody reactive clone (LYAR). The results showed that LINC00355 was upregulated in lung SCC and was positively associated with poor overall survival in lung SCC patients. LINC00355 was mainly located in the cytoplasm of SCC cells. Additionally, LINC0035 functioned as a competing endogenous RNA (ceRNA) to target miR-466, and LYAR was identified as a direct target of miR-466. LINC00355 expression negatively correlated with miR-466 level, and positively correlated with LYAR level. Mechanistically, knockdown of LINC00355 inhibited cell proliferation, migration and invasion, promoted cell apoptosis in vitro, and suppressed tumor growth in vivo through targeting miR-466, and thus down-regulated LYAR expression. These findings provide a new sight for understanding the molecular mechanism of lung SCC and indicate that LINC00355 may serve as a potential biomarker for the diagnosis and treatment of lung SCC.

Resumo em Inglês:

Previous analyses of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) identified four main dietary patterns (DP). The aim of this study was to explore the association between the previously defined DP and renal function (RF). A cross-sectional study using the ELSA-Brasil baseline data was carried out. DP (“traditional”, “fruits and vegetables”, “bakery”, and “low sugar/low fat), metabolic syndrome (MS) using the Joint Interim Statement criteria, microalbuminuria (MA), and glomerular filtration rate (eGFR) through the CKD-EPI equation were evaluated. Abnormal RF was defined as eGFR<60 mL·min-1·(1.73 m2)-1 and MA≥3.0 mg/dL. Factors associated with RF were determined and mediation analysis was performed to investigate the association between DP, MS, and RF. A total of 15,105 participants were recruited, with a mean age of 52±9 years; 8,134 participants (54%) were females. The mediation analysis identified indirect associations between “bakery” and “fruits and vegetables”, and both were associated with decreased eGFR and albuminuria in both genders, compared with “traditional” and “low sugar/low fat” patterns in the general population. There was a direct association of the “bakery” pattern with MA in men (OR: 1.17, 95%CI: 1.92-1.48). The “fruits and vegetables” pattern also showed a direct association with reduced eGFR in women (OR: 1.65, 95%CI: 1.28-2.12), although there was no significance after adjustment. The “fruits and vegetables” and “bakery” DPs were associated with renal dysfunction. The only independent, direct association was between “bakery” DP and MA in men, raising concerns about DP and renal damage in men.

Resumo em Inglês:

Recent evidence suggests that glaucoma and Alzheimer's disease are neurodegenerative diseases sharing common pathophysiological and etiological features, although findings are inconclusive. We sought to investigate whether self-reported glaucoma patients without dementia present poorer cognitive performance, an issue that has been less investigated. We employed cross-sectional data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) and included participants ≥50 years of age without a known diagnosis of dementia and a self-reported glaucoma diagnosis. We excluded those with previous stroke, other eye conditions, and using drugs that could impair cognition. We evaluated cognition using delayed word recall, phonemic verbal fluency, and trail making (version B) tests. We used multinomial linear regression models to investigate associations between self-reported glaucoma with cognition, adjusted by several sociodemographic and clinical variables. Out of 4,331 participants, 139 reported glaucoma. Fully-adjusted models showed that self-reported glaucoma patients presented poorer performance in the verbal fluency test (β=-0.39, 95%CI=-0.64 to -0.14, P=0.002), but not in the other cognitive assessments. Thus, our results support the hypothesis that self-reported glaucoma is associated with poor cognitive performance; however, longitudinal data are necessary to corroborate our findings.

Resumo em Inglês:

The sympathetic nervous system (SNS) plays a fundamental role in the pathophysiology of cardiovascular diseases, including primary arterial hypertension. In this study, we aimed to investigate whether the expression of the rate-limiting enzyme in catecholamine synthesis, tyrosine hydroxylase (TH), and the β2-adrenergic receptor (β2-AR) in immune cells from peripheral blood, reflect central SNS activity in spontaneously hypertensive rats (SHR). TH expression in the lower brainstem and adrenal glands and β2-AR expression in the lower brainstem were analyzed by western blot analyses. In the leukocytes, TH and β2-AR expression was evaluated by flow cytometry before and after chronic treatment with the centrally-acting sympathoinhibitory drug clonidine. Western blot analyses showed increased TH and β2-AR expression in the lower brainstem and increased TH in adrenal glands from SHR compared to normotensive Wistar Kyoto rats (WKY). Lower brainstem from SHR treated with clonidine presented reduced TH and β2-AR levels, and adrenal glands had decreased TH expression compared to SHR treated with vehicle. Flow cytometry showed that the percentage of leukocytes that express β2-AR is higher in SHR than in WKY. However, the percentage of leukocytes that expressed TH was higher in WKY than in SHR. Moreover, chronic treatment with clonidine normalized the levels of TH and β2-AR in leukocytes from SHR to similar levels of those of WKY. Our study demonstrated that the percentage of leukocytes expressing TH and β2-AR was altered in arterial hypertension and can be modulated by central sympathetic inhibition with clonidine treatment.

Resumo em Inglês:

The aim of this study was to evaluate the antimicrobial activity and toxicity of glass ionomer cement (GIC) modified with 5-methyl-2-(1-methylethyl)phenol (thymol) against Streptococcus mutans in silico and in vitro. The antimicrobial activity of thymol on GIC modified with concentrations of 2% (GIC-2) and 4% (GIC-4) was evaluated in a model of planktonic cell biofilm using agar diffusion test, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), dynamic biofilm (continuous flow cell parallel), and bacterial kinetics. Conventional GIC (GIC-0) was used as a control. Thymol toxicity was evaluated in Artemia salina and in silico using Osiris® software. Differences between groups were estimated by analysis of variance, followed by Tukey post hoc test, with a 5% significance level. The results of the agar diffusion test between groups were not significantly different (P≥0.05). Thymol had potential bacteriostatic and bactericidal activity against Streptococcus mutans with respect to planktonic growth, with MIC of 100 µg/mL and MBC of 400 µg/mL. The groups GIC-0, GIC-2, and GIC-4 reduced the biofilm by approximately 10, 85, and 95%, respectively. Bacterial kinetics showed efficiency of the modified GICs for up to 96 h. GIC with thymol was effective against S. mutans, with significant inhibition of the biofilms. Analyses in silico and using Artemia salina resulted in no relevant toxicity, suggesting potential for use in humans. GIC-2 was effective against S. mutans biofilm, with decreased cell viability.

Resumo em Inglês:

Psoriasis is a chronic inflammatory skin disorder in humans, and the inflammatory reaction plays an important role in development and onset of psoriasis. 4'-O-β-D-glucosyl-5-O-methylvisamminol (4GMV) is one of the major active chromones isolated from Saposhnikoviae divaricata (Turcz.) Schischk, which has been reported to exhibit excellent anti-inflammatory activities. However, the possible therapeutic effect on psoriasis and underlying mechanism has not been reported. Thus, the aim of this study was to investigate the protective effect of 4GMV on the imiquimod (IMQ)-induced psoriasis-like lesions in BALB/c mice and the anti-inflammatory effect on the lipopolysaccharide (LPS)-induced inflammation in RAW264.7 macrophages. The results demonstrated that 4GMV decreased IMQ-induced keratinocyte proliferation and inflammatory cell infiltration. Moreover, 4GMV treatment significantly inhibited the production of NO, PEG 2, and cytokines such as interleukin (IL)-1β, IL-6, interferon (IFN)-γ, and IL-22 in LPS-stimulated RAW264.7 macrophages. 4GMV also suppressed the LPS-upregulated protein expressions of iNOS and COX-2 in a dose-dependent manner. Furthermore, qRT-PCR analysis showed that 4GMV down-regulated the mRNA level of IL-1β and IL-6 expression. Further studies by western blot indicated that 4GMV inhibited the activation of upstream mediator NF-κB by suppressing the expression of TLR4 and the phosphorylation of IκBα and p65. The phosphorylation of JNK, p38, and ERK were also markedly reversed by 4GMV in LPS-treated RAW264.7 macrophages. Taken together, these results demonstrated that 4GMV showed a protective effect in IMQ-induced psoriasis-like mice and inhibited inflammation through the NF-κB and MAPK signaling pathways, indicating that 4GMV might be a potential therapeutic drug for psoriasis.

Resumo em Inglês:

This study aimed to explore the association between serum non-high-density lipoprotein cholesterol (non-HDL-C) and cognitive dysfunction risk in patients with acute ischemic stroke (AIS). This cross-sectional study enrolled 583 AIS patients. Biochemical markers and lipid profile were collected after admission. AIS patients were classified into high group (non-HDL-C ≥3.4 mM) and normal group (non-HDL-C <3.4 mM). Mini-Mental State Examination scale (MMSE), Montreal Cognitive Assessment scale (MoCA), Activities of Daily Living (ADL) scale, Neuropsychiatric Inventory (NPI), and Hamilton Depression scale 21 version (HAMD-21) were applied on the third day after admission. Compared with the control group, patients of the high group had higher body mass index and higher frequency of intracranial artery stenosis, and exhibited higher levels of non-HDL-C, total cholesterol, triglycerides, low-density lipoprotein cholesterol, homocysteine, fasting blood glucose, and glycosylated hemoglobin (HbA1c), and lower levels of high-density lipoprotein cholesterol (all P<0.05). Compared with the control group, patients of the high group had significantly lower MMSE and MoCA scores (MMSE: 26.01±4.17 vs 23.12±4.73, P<0.001; MoCA: 22.28±5.28 vs 20.25±5.87, P<0.001) and higher scores on the NPI and HAMD-21 (both P<0.001). MMSE (r=-0.306, P<0.001) and MoCA scores (r=-0.251, P<0.001) were negatively associated with non-HDL-C level. Multivariate regression analysis revealed that non-HDL-C level (OR=1.361, 95%CI: 1.059-1.729, P=0.016) was independently associated with the presence of cognitive dysfunction after adjusting for confounding factors. High serum non-HDL-C level might significantly increase the risk of cognitive dysfunction after AIS.

Resumo em Inglês:

Breast cancer (BC) is a commonly diagnosed cancer in females. MicroRNA-660-5p (miR-660-5p) has been reported to be involved in the occurrence and development of BC. However, the regulatory network of miR-660-5p in BC has not been fully addressed. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the enrichment of miR-660-5p and tet-eleven translocation 2 (TET2) in BC tissues and cells. Cell counting kit-8 (CCK8), flow cytometry, and transwell migration and invasion assays were used to measure cell proliferation, apoptosis, migration, and invasion. The target relationship between miR-660-5p and TET2 was confirmed by dual luciferase reporter assay. Protein expression was measured by western blot. The expression of miR-660-5p was elevated in BC, and high expression of miR-660-5p was closely related to lymph node metastasis, advanced TNM stage, and vascular invasion of BC tumors. miR-660-5p silencing inhibited cell proliferation and metastasis, but induced apoptosis of BC cells. TET2 was identified as a direct target of miR-660-5p, and the interference of TET2 partly reversed the suppressive effects of miR-660-5p silencing on the malignant potential of BC cells. miR-660-5p promoted BC progression partly through modulating TET2 and PI3K/AKT/mTOR signaling. miR-660-5p/TET2 axis might be a promising target for BC treatment.