Background and Purpose
A long‐term imbalance between pro‐ and anti‐inflammatory mediators leads to airway remodelling, which is strongly correlated to most of the symptoms, severity and progression ...of chronic lung inflammation. The Angiotensin‐(1‐7) Ang‐(1‐7)/Mas receptor axis of the renin‐angiotensin system is associated with attenuation of acute and chronic inflammatory processes. In this study, we investigated the effects of Ang‐(1‐7) treatment in a model of chronic allergic lung inflammation.
Experimental Approach
Mice were sensitized to ovalbumin (OVA; 4 injections over 42 days, 14 days apart) and were challenged three times per week (days 21–46). These mice received Ang‐(1‐7) (1 μg·h−1, s.c.) by osmotic mini‐pumps, for the last 28 days. Histology and morphometric analysis were performed in left lung and right ventricle. Airway responsiveness to methacholine, analysis of Ang‐(1‐7) levels (RIA), collagen I and III (qRT‐PCR), ERK1/2 and JNK (Western blotting), IgE (elisa), cytokines and chemokines (elisa multiplex), and immunohistochemistry for Mas receptors were performed.
Key Results
Infusion of Ang‐(1‐7) in OVA‐sensitized and challenged mice decreased inflammatory cell infiltration and collagen deposition in the airways and lung parenchyma, and prevented bronchial hyperresponsiveness. These effects were accompanied by decreased IgE and ERK1/2 phosphorylation, and decreased pro‐inflammatory cytokines. Mas receptors were detected in the epithelium and bronchial smooth muscle, suggesting a site in the lung for the beneficial actions of Ang‐(1‐7).
Conclusions and Implications
Ang‐(1‐7) exerted beneficial attenuation of three major features of chronic asthma: lung inflammation, airway remodelling and hyperresponsiveness. Our results support an important protective role of Ang‐(1‐7) in lung inflammation.
Abstract
Dark magnetic spots crossing the stellar disk lead to quasiperiodic brightness variations, which allow us to constrain stellar surface rotation and photometric activity. The current work is ...the second of this series, where we analyze the Kepler long-cadence data of 132,921 main-sequence F and G stars and late subgiant stars. Rotation-period candidates are obtained by combining wavelet analysis with autocorrelation function. Reliable rotation periods are then selected via a machine-learning (ML) algorithm, automatic selection, and complementary visual inspection. The ML training data set comprises 26,521 main-sequence K and M stars from Paper I. To supplement the training, we analyze in the same way as Paper I, i.e., automatic selection and visual inspection, 34,100 additional stars. We finally provide rotation periods
P
rot
and associated photometric activity proxy
S
ph
for 39,592 targets. Hotter stars are generally faster rotators than cooler stars. For main-sequence G stars,
S
ph
spans a wider range of values with increasing effective temperature, while F stars tend to have smaller
S
ph
values in comparison with cooler stars. Overall for G stars, fast rotators are photometrically more active than slow rotators, with
S
ph
saturating at short periods. The combined outcome of the two papers accounts for average
P
rot
and
S
ph
values for 55,232 main-sequence and subgiant FGKM stars (out of 159,442 targets), with 24,182 new
P
rot
detections in comparison with McQuillan et al. The upper edge of the
P
rot
distribution is located at longer
P
rot
than found previously.
Colorectal cancer (CRC) screening relies primarily on stool analysis to identify occult blood. However, its sensitivity for detecting precancerous lesions is limited, requiring the development of new ...tools to improve CRC screening. Carcinogenesis involves significant alterations in mucosal epithelium glycocalyx that decisively contribute to disease progression. Building on this knowledge, we examined patient series comprehending premalignant lesions, colorectal tumors, and healthy controls for the T-antigen-a short-chain
-glycosylation of proteins considered a surrogate marker of malignancy in multiple solid cancers. We found the T-antigen in the secretions of dysplastic lesions as well as in cancer. In CRC, T-antigen expression was associated with the presence of distant metastases. In parallel, we analyzed a broad number of stools from individuals who underwent colonoscopy, which showed high T expressions in high-grade dysplasia and carcinomas. Employing mass spectrometry-based lectin-affinity enrichment, we identified a total of 262 proteins, 67% of which potentially exhibited altered glycosylation patterns associated with cancer and advanced pre-cancerous lesions. Also, we found that the stool (glyco)proteome of pre-cancerous lesions is enriched for protein species involved in key biological processes linked to humoral and innate immune responses. This study offers a thorough analysis of the stool glycoproteome, laying the groundwork for harnessing glycosylation alterations to improve non-invasive cancer detection.
Colorectal cancer (CRC) ranks as the third most prevalent cancer worldwide. Early detection of this neoplasia has proven to improve prognosis, resulting in a 90% increase in survival. However, ...available CRC screening methods have limitations, requiring the development of new tools. MicroRNA biomarkers have emerged as a powerful screening tool, as they are highly expressed in CRC patients and easily detectable in several biological samples. While microRNAs are extensively studied in blood samples, recent interest has now arisen in other samples, such as stool samples, where they can be combined with existing screening methods. Among the microRNAs described in the literature, microRNA-21-5p and microRNA-92a-3p and their cluster have demonstrated high potential for early CRC screening. Furthermore, the combination of multiple microRNAs has shown improved performance in CRC detection compared to individual microRNAs. This review aims to assess the available data in the literature on microRNAs as promising biomarkers for early CRC screening, explore their advantages and disadvantages, and discuss the optimal study characteristics for analyzing these biomarkers.
We present Q-U-I JOint TEnerife (QUIJOTE) intensity and polarisation maps at 10-20 GHz covering a region along the Galactic plane 24... l ... 45..., |b| ... 8... These maps result from 210 h of data, ...have a sensitivity in polarisation of ...40 ...K beam super( -1) and an angular resolution of ...1... Our intensity data are crucial to confirm the presence of anomalous microwave emission (AME) towards the two molecular complexes W43 (22...) and W47 (8...). We also detect at high significance (6...) AME associated with W44, the first clear detection of this emission towards a supernova remnant. The new QUIJOTE polarisation data, in combination with Wilkinson Microwave Anisotropy Probe (WMAP), are essential to (i) determine the spectral index of the synchrotron emission in W44, ... = -0.62 plus or minus 0.03, in good agreement with the value inferred from the intensity spectrum once a free-free component is included in the fit; (ii) trace the change in the polarisation angle associated with Faraday rotation in the direction of W44 with rotation measure -404 plus or minus 49 rad m super( -2) and (iii) set upper limits on the polarisation of W43 of ... < 0.39 per cent (95 per cent C.L.) from QUIJOTE 17 GHz, and <0.22 per cent from WMAP 41 GHz data, which are the most stringent constraints ever obtained on the polarisation fraction of the AME. For typical physical conditions (grain temperature and magnetic field strengths), and in the case of perfect alignment between the grains and the magnetic field, the models of electric or magnetic dipole emissions predict higher polarisation fractions. (ProQuest: ... denotes formulae/symbols omitted.)
Objective To describe the laboratory parameters and biomarkers of the cytokine storm syndrome associated with severe and fatal COVID-19 cases. Methods A search with standardized descriptors and ...synonyms was performed on November 28.sup.th, 2020 of the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, LILACS, and IBECS to identify studies of interest. Grey literature searches and snowballing techniques were additionally utilized to identify yet-unpublished works and related citations. Two review authors independently screened the retrieved titles and abstracts, selected eligible studies for inclusion, extracted data from the included studies, and then assessed the risk of bias using the Newcastle-Ottawa Scale. Eligible studies were those including laboratory parameters-including serum interleukin-6 levels-from mild, moderate, or severe COVID-19 cases. Laboratory parameters, such as interleukin-6, ferritin, hematology, C-Reactive Protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, creatinine, and D-dimer, were extracted from the studies. Meta-analyses were conducted using the laboratory data to estimate mean differences with associated 95% confidence intervals. Data synthesis The database search yielded 9,620 records; 40 studies (containing a total of 9,542 patients) were included in the final analysis. Twenty-one studies (n = 4,313) assessed laboratory data related to severe COVID-19 cases, eighteen studies (n = 4,681) assessed predictors for fatal COVID-19 cases and one study (n = 548) assessed laboratory biomarkers related to severe and fatal COVID-19 cases. Lymphopenia, thrombocytopenia, and elevated levels of interleukin-6, ferritin, D-dimer, aspartate aminotransferase, C-Reactive-Protein, procalcitonin, creatinine, neutrophils and leucocytes were associated with severe and fatal COVID-19 cases. Conclusions This review points to interleukin-6, ferritin, leukocytes, neutrophils, lymphocytes, platelets, C-Reactive Protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, creatinine, and D-dimer as important biomarkers of cytokine storm syndrome. Elevated levels of interleukin-6 and hyperferritinemia should be considered as red flags of systemic inflammation and poor prognosis in COVID-19.
Familial hypercholesterolemia (FH) is characterized by high low-density lipoprotein cholesterol (LDL-C) levels and a high risk of early coronary heart disease. Structural alterations in the LDLR, ...APOB, and PCSK9 genes were not found in 20-40% of patients diagnosed using the Dutch Lipid Clinic Network (DCLN) criteria. We hypothesized that methylation in canonical genes could explain the origin of the phenotype in these patients. This study included 62 DNA samples from patients with a clinical diagnosis of FH according to the DCLN criteria, who previously tested negative for structural alterations in the canonical genes, and 47 DNA samples from patients with normal blood lipids (control group). All DNA samples were tested for methylation in the CpG islands of the three genes. The prevalence of FH relative to each gene was determined in both groups and the respective prevalence ratios (PRs) were calculated. The methylation analysis of APOB and PCSK9 was negative in both groups, showing no relationship between methylation in these genes and the FH phenotype. As the LDLR gene has two CpG islands, we analyzed each island separately. The analysis of LDLR-island1 showed PR = 0.982 (CI 0.33-2.95; χ
= 0.001; p = 0.973), also suggesting no relationship between methylation and the FH phenotype. Analysis of LDLR-island2 showed a PR of 4.12 (CI 1.43-11.88; χ
= 13,921; p = 0.00019), indicating a possible association between methylation on this island and the FH phenotype.
The purpose of this study was to assess the impact of 24 wk of resistance training at two different intensities on cognitive functions in the elderly.
Sixty-two elderly individuals were randomly ...assigned to three groups: CONTROL (N = 23), experimental moderate (EMODERATE; N = 19), and experimental high (EHIGH; N = 20). The volunteers were assessed on physical, hemodynamic, cognitive, and mood parameters before and after the program.
On the 1 RM test (P < 0.001), the two experimental groups performed better than the CONTROL group, but they did not show differences between themselves. The EHIGH group gained more lean mass (P = 0.05) than the CONTROL group and performed better on the following tests: digit span forward (P < 0.001), Corsi's block-tapping task backward (P = 0.001), similarities (P = 0.03), Rey-Osterrieth complex figure immediate recall (P = 0.02), Toulouse-Pieron concentration test errors (P = 0.01), SF-36 (general health) (P = 0.04), POMS (tension-anxiety, P = 0.04; depression-dejection, P = 0.03; and total mood disorder, P = 0.03). The EMODERATE group scored higher means than the CONTROL group on digit span forward (P < 0.001), Corsi's block-tapping task backward (P = 0.01), similarities (P = 0.02), Rey-Osterrieth complex figure immediate recall (P = 0.02), SF-36 (general health, P = 0.005; vitality, P = 0.006), POMS (tension-anxiety, P = 0.001; depression-dejection, P = 0.006; anger-hostility, P = 0.006; fatigue-inertia, P = 0.02; confusion-bewilderment, P = 0.02; and total mood disorder, P = 0.001). We also found that IGF-1 serum levels were higher in the experimental groups (EMODERATE, P = 0.02; EHIGH, P < 0.001).
Moderate- and high-intensity resistance exercise programs had equally beneficial effects on cognitive functioning.
The guidelines for the Environmental Risk Assessment (ERA) of pharmaceuticals and personal care products (PPCP) recommend the use of standard ecotoxicity assays and the assessment of endpoints at the ...individual level to evaluate potential effects of PPCP on biota. However, effects at the sub-individual level can also affect the ecological fitness of marine organisms chronically exposed to PPCP. The aim of the current study was to evaluate the environmental risk of two PPCP in marine sediments: triclosan (TCS) and ibuprofen (IBU), using sub-individual and developmental endpoints. The environmental levels of TCS and IBU were quantified in marine sediments from the vicinities of the Santos submarine sewage outfall (Santos Bay, São Paulo, Brazil) at 15.14 and 49.0 ng g−1, respectively. A battery (n = 3) of chronic bioassays (embryo-larval development) with a sea urchin (Lytechinus variegatus) and a bivalve (Perna perna) were performed using two exposure conditions: sediment-water interface and elutriates. Moreover, physiological stress through the Neutral Red Retention Time Assay (NRRT) was assessed in the estuarine bivalve Mytella charruana exposed to TCS and IBU spiked sediments. These compounds affected the development of L. variegatus and P. perna (75 ng g−1 for TCS and 15 ng g−1 for IBU), and caused a significant decrease in M. charruana lysosomal membrane stability at environmentally relevant concentrations (0.08 ng g−1 for TCS and 0.15 ng g−1 for IBU). Chemical and ecotoxicological data were integrated and the risk quotient estimated for TCS and IBU were higher than 1.0, indicating a high environmental risk of these compounds in sediments. These are the first data of sediment risk assessment of pharmaceuticals and personal care products of Latin America. In addition, the results suggest that the ERA based only on individual-level and standard toxicity tests may overlook other biological effects that can affect the health of marine organisms exposed to PPCP.
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•Triclosan and ibuprofen were quantified in order of ng.g-1 in marine sediment.•Adverse effects were found in environmentally relevant concentrations.•Mytella charruana is an alternative species for monitoring marine and estuarine sediments.•Significant environmental risk for triclosan and ibuprofen in a tropical coastal zone.
This study presents the first data of sediment risk assessment of pharmaceuticals and personal care products in Latin America.
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