Notes

Facts accumulation concerns perceptual mindset and overseeing.
ulmonary function and physical activity might attenuate the adverse effects of PM2.5 among populations at intermediate to high-risk of CVD. These findings provide new robust evidence on health effects of air pollution and call for effective prevention measures among people at CVD risk.Presently, toxicological assessment of multiple veterinary antimicrobials has not been performed on mammals. In this study, we assessed the short-term toxicity of enrofloxacin (E) combined with colistin (C) and quinocetone (Q). Young male rats were orally dosed drug mixtures and single drugs in 14 consecutive days, each at the dose of 20, 80, and 400 mg/(kg·BW) for environmental toxicologic study. The results showed that at the high dose treatment, the combination of E + C+Q significantly decreased body intake, lymphocytes count on rats; significantly increased the values of Alanine aminotransferase (ALT), Glutamic oxaloacetic transaminase (AST) and, cholinesterase (CHE); it also got the severest histopathological changes, where sinusoidal congestion and a large number of black particles in sinusoids were observed. AZD9291 research buy This means E + C+Q in the high dose groups was able to cause significant damage to the liver. Other combinations or doses did not induce significant liver damage. Transcriptome analysis was then performed on rats in high dose group for further research. For E + C and E + Q, an amount of 375 and 480 differently expressed genes were filtered out, revealing their possible underlying effect on genomes. For E + C+Q, a weighted gene co-expression network analysis was performed and 96 hub genes were identified to reveal the specific effect induced by this combination. This study indicates that joint toxicity should be taken into consideration when involving the risk assessment of these antimicrobials.A novel coronavirus (SARS-CoV-2) has caused more than 150 million confirmed infections worldwide, while it is not clear whether it affects the coastal waters. This paper proposed a biophysical model based on 16 scenarios with different virus half-life parameters to assess potential viral contamination from 25 municipal sewage outfalls into the Bohai Sea. Viral concentration maps showing spatial and temporal changes are provided based on a biophysical model under multiple scenarios. Results demonstrate that adjacent sea areas can become exposed to SARS-CoV-2 via water-borne transport from outfalls, with a higher risk in winter, because SARS-CoV-2 can be highly stable at low temperature. As coastal waters are the ultimate sink for wastewater and the epidemic will last for long time, this work is of great importance to raise awareness, identify vulnerable areas for marine mammals, and avoid the risk of exposure of tourists at bathing beach.The associations of bisphenol A exposure during pregnancy with risk of preterm birth (PTB) and changes in gestational age have remained controversial. To conduct the meta-analysis, the relevant studies were searched through PubMed, OVID, and Web of Science from inception through June ‎17, ‎2020. Data were independently extracted and analyzed using odds ratio (OR) or regression coefficient (β) and their 95% confidence intervals (CIs). We identified 668 references and included 7 studies for preterm birth and 9 studies for gestational age. The included studies reported that the median or geometric mean (GM) of maternal urinary BPA ranged from 0.48 to 6.44 ng/ml. The meta-analysis estimated OR to be 1.36 (95% CI 1.03, 1.69) for preterm birth associated with maternal urinary BPA exposure during pregnancy. In the subgroup analysis based on BPA exposure level, a significant association was observed between preterm birth and higher BPA exposure among the populations had BPA median or GM concentrations higher than 2.16 ng/ml (OR 1.92; 95% CI 1.38, 2.47). In the subgroup analyses by maternal urinary BPA exposure assessed in different trimesters, a significant association of preterm birth was only observed with BPA assessed in the third trimester (OR 1.62; 95% CI 1.15, 2.09). In addition, higher maternal urinary BPA exposure during pregnancy was associated with decreased gestational age by 0.50 (-0.87, -0.13) days, and the subgroup analyses also showed that only BPA exposure in the third trimester was associated with decreased gestational age by 1.36 (-2.21, -0.52) days. This meta-analysis demonstrated that higher BPA exposure was associated with an increased risk of preterm birth and decreased length of gestational age, and suggested that BPA exposure in the third trimester of pregnancy may be a critical susceptible period of preterm birth.
Azithromycin reduced airway remodeling in animal models of asthma. However, its effect on human subjects has not been studied yet. This study aimed to investigate the effect of long-term treatment with azithromycin on airways wall thickness in patients with severe persistent asthma.

In this randomized, double-blind, placebo-controlled clinical trial, patients with severe persistent asthma received azithromycin (250mg, BID, three days a week), prednisolone (5mg, BID), or placebo for eight months in three separate groups in addition to the standard therapy. The improvement in right upper lobe apical segmental bronchus (RB1) wall thickness obtained by high resolution computed tomography was set as the primary outcome. Secondary outcomes included cough severity, dyspnea severity, asthma control test (ACT) score, asthma exacerbation rate, pulmonary function tests, and fractional exhaled nitric oxide (FENO).

Seventy-eight out of ninety randomized subjects completed eight months of treatment with azithromycin (n=25), prednisolone (n=27), or placebo (n=26). Bronchial wall thickness percentage did not change significantly in any of the groups. However, the inner radius and lumen area of azithromycin and prednisolone-treated subjects increased significantly (p<0.05 for both). Azithromycin also significantly improved the dyspnea severity, ACT score, FENO, and FEV1, FEF
, and FEV1/FVC (p<0.05 for all). Cough severity or asthma exacerbation rate did not change significantly after eight months of treatment with azithromycin.

Long-term treatment with azithromycin increased lumen radius and lumen area in patients with severe persistent asthma. However, there was no significant change in wall thickness in any of the treatment groups.

IRCT.com (IRCT20091111002695N8).
IRCT.com (IRCT20091111002695N8).
Lung function impairment in COPD is known to be related to reductions of left heart size, while short-term interventional trials with bronchodilators showed positive effects on cardiac parameters. We investigated whether COPD maintenance therapy has analogous long-term effects.

Pooled data of GOLD grade 1-4 patients from visits 1 and 3 (1.5y apart) of the COSYCONET cohort were used. Medication was categorized as use of ICS, LABA+ICS, LABA+LAMA and triple therapy (LABA+LAMA+ICS), contrasting "always" versus "never". Echocardiographic parameters comprised left ventricular end-diastolic and -systolic diameter (LVEDD, LVESD), ejection fraction (LVEF) and left atrial diameter (LA). Associations were identified by multiple regression analysis, as well as propensity score analysis.

Overall, 846 patients (mean age 64.5y; 41% female) were included, 53% using ICS at both visits, 51% LABA+ICS, 56% LABA+LAMA, 40% LABA+LAMA+ICS (triple) therapy. Conversely, 30%, 32%, 28% and 42% had no ICS, LABA+ICS, LABA+LAMA or triple therapy, respectively, at both visits. Among echocardiographic measures, only LA showed statistically significant associations (increases) with medication, whereby significant effects were linked to ICS, LABA+ICS and LABA+LAMA (p<0.05 each, "always" versus "never") and propensity score analyses underlined the role of LABA+LAMA.

In this observational study, COPD maintenance therapy, especially LABA+LAMA, was linked to left atrial size, consistent with the results of short-term interventional trials. These findings suggest that maintenance medication for COPD does not only improve lung function and patient reported outcomes but may also have an impact on the cardiovascular system.

NCT01245933.
NCT01245933.The aim of this study was to synthesize chalcone-polyamine conjugates in order to enhance bioavailability and selectivity of chalcone core towards cancer cells, using polyamine-based vectors. Indeed, it is well-known that polyamine transport system is upregulated in tumor cells. 3',4,4',5'-tetramethoxychalcone was selected as parent chalcone since it was found to be an efficient anti-proliferative agent on various cancer cells. A series of five chalcone-polyamine conjugates was obtained using the 4-bromopropyloxy-3',4',5'-trimethoxychalcone as a key intermediate. Chalcone core and polyamine tails were fused through an amine bond. These conjugates were found to possess a marked in vitro antiproliferative effect against colorectal (HT-29 and HCT-116) and prostate cancer (PC-3 and DU-145) cell lines. The most active conjugate (compound 8b) was then chosen for further biological evaluations to elucidate mechanisms responsible for its antiproliferative activity. Investigations on cell cycle distribution revealed that this conjugate can prevent the proliferation of human colorectal and prostate cancer cells by blocking the cell cycle at the G1 and G2 phase, respectively. Flow cytometry analysis revealed a sub-G1 peak, characteristic of apoptotic cell population and our inquiries highlighted apoptosis induction at early and later stages through several pro-apoptotic markers. Therefore, this chalcone-N1-spermidine conjugate could be considered as a promising agent for colon and prostatic cancer adjuvant therapy.Matrix metalloproteinase-9 (MMP-9) and monoamine oxidase-A (MAO-A) are central signaling nodes in CRC and promotors of distant metastasis associated with high mortality rates. Novel series of quinoxaline-based dual MMP-9/MAO-A inhibitors were synthesized to suppress CRC progression. The design rationale combines the thematic pharmacophoric features of MMP-9 and MAO-A inhibitors in hybrid scaffolds. All derivatives were initially screened via MTT assay for cytotoxic effects on normal colonocytes to assess their safety profiles, then evaluated for their anticancer potential on HCT116 cells overexpressing MMP-9 and MAO-A. The most promising derivatives 8, 16, 17, 19, and 28 exhibited single digit nanomolar IC50 against HCT116 cells within their safe doses (EC100) on normal colonocytes. They suppressed HCT116 cell migration by 73.32, 61.29, 21.27, 28.82, and 27.48%, respectively as detected by wound healing assay. Enzymatic assays revealed that the selected derivatives were superior to the reference MMP-9 and MAO-A inhibitors (quercetin and clorgyline, respectively). The nanomolar dual MMP-9/MAO-A inhibitor 19 was identified as the most potent and balanced dual inhibitor among the evaluated series with considerable selectivity against MAO-A over MAO-B. Besides, qRT-PCR analysis was conducted to explore the hit compounds' potential to downregulate hypoxia-inducing factor (HIF-1α) in HCT116 cells being correlated with MAO-A mediated CRC migration and invasion. The five above-mentioned compounds significantly downregulated HIF-1α by more than 5 folds. Docking simulations predicted their possible binding modes with MMP-9 and MAO-A and highlighted their essential structural features. Finally, they recorded drug-like in silico physicochemical parameters and ADMET profiles.
Homepage: https://www.selleckchem.com/products/azd9291.html