Goffsantiago5846

Autophagy is a major cause of pathological vascular remodeling under hypoxic pulmonary hypertension (PH). Sirtuin 3 (Sirt 3) has recently been reported to be involved in the regulation of autophagy, however, its role as an autophagy regulator during hypoxic PH, particularly the molecular mechanism, remains poorly understood. In the present study, Western blot, immunohistochemistry, immunofluorescence, bromodeoxyuridine incorporation and cell cycle analyses were performed to elucidate the underlying mechanism of hypoxia-induced autophagy and cell proliferation with respect to Sirt 3. We observed that the Sirt 3 expression was decreased under hypoxia and that Sirt 3 overexpression significantly inhibited the effects of hypoxia on autophagy. Next, we investigated the mechanistic role of microRNAs in Sirt 3-associated autophagy under hypoxic conditions, with luciferase reporter, microscale thermophoresis and RNA immunoprecipitation assays, results confirming that Sirt 3 is a direct target of miR-874-5p. Furthermore, miR-874-5p was upregulated following hypoxia, and miR-874-5p depletion in turn inhibited autophagy and consequently suppressed abnormal smooth muscle cell proliferation. These findings provide insight into the contribution of the miR-874-5p/Sirt 3 cascade with regard to changes in autophagy and proliferation associated with PH.Non-small cell lung cancer (NSCLC) is the most frequent type of lung cancer accounting up to 80-85% of all lung cancer (LC) cases. Gemcitabine (Gem), a pyrimidine nucleoside antimetabolite, is widely used chemotherapy offering several months survival benefit in patients with NSCLC. The emergence of Gem resistance is a main clinical concern in cancer treatment and thus a continuous demand for development of new therapeutic strategies to improve its antitumor activity. Hence, we report an adjuvant therapeutic regimen based on natural compound, gambogic acid (GA) which has been shown to enhanced Gem induced inhibition of cancer cell growth, arrest cell cycle, and induce apoptosis by enhanced accumulation of Gem. The in vitro cell viability, clonogenicity, invasion, and migration assays demonstrated a significant higher therapeutic effect of Gem when it was combined with GA in A549 and H1299 cells. A better access of internalization of drug molecules achieved in rhodamine 123 assay when GA was used as adjuvant treatment. Further, GA and Gem combination significantly reduced tubular formation of HUVEC cells indicates lowering angiogenesis potential. Microarray and Western blot studies confirm that GA + Gem co-treatment strategy promotes cancer cell death by downregulating anti-apoptotic proteins, chemoresistance-associated proteins, and upregulation of apoptosis proteins. More importantly, a significant higher therapeutic benefit was noticed for GA and Gem combination in A549 xenograft mice model. Together, these results offer a rationale to evaluate the clinical translational possibility of GA as adjuvant therapy to overcome Gem resistance. This combination regimen can be a new therapeutic concept to eradicate this devastating disease.Therapies of cancer are as diverse as multifaceted the cancer is. Anticancer drugs include, but not limited to synthetic, semisynthetic and natural drugs and monoclonal antibodies. A recent decline in new drug development has led to the rebirth of herbal therapeutics in the form of dietary supplements and botanical preparations. Medicinal plants comprise of complex phytochemicals due to vast biosynthetic capacity. A wide array of phytochemicals has been pharmacologically evaluated for their chemo-preventive and chemotherapeutic potential for several decades. These phytochemicals target cancer at diverse sites such as apoptotic pathways, genetic and epigenetic mutations, damage to deoxyribonucleic acid, production of reactive oxygen species, autophagy, invasion and metastasis of cancer cells, and modulation of cell signaling through Janus-activated kinase/Signal transducer and activator of transcription, Notch, mitogen-activated protein kinase/Extracellular signal-regulated kinase, phosphatidylinositol 3-kinase/Protein kinase B/mammalian target of rapamycin, Nuclear factor kappa B, Wingless-related integration site and Transforming growth factor β pathways. This review focuses on the therapeutic targets of anticancer and chemo-preventive phytochemicals and their mode of action.

This study was aimed to identify an accurate gene expression signature to predict overall survival (OS) in patients with ovarian cancer (OC).

Expression data and corresponding clinical information were obtained from two independent databases the Cancer Genome Atlas (TCGA) dataset and International Cancer Genome Consortium (ICGC) dataset. Multiple analysis methods including univariate and multivariate COX regression analysis and Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis were utilized to build the signature. Receiver operating characteristic (ROC) and Kaplan-Meier (KM) survival analyses were used to assess the predictive accuracy of this gene signature.

A novel 10-gene signature with high predictive accuracy for OS in OC patients was constructed and validated in the training and validation set. Based on the results of univariate and multivariate analyses, the presence of risk Score was identified as an independent prognostic factor for survival of OC patients. Moreover, we developed a nomogram model based on these 10 genes in the signature, which also displayed a favorable predictive efficacy for prognosis in OC.

Our results identified a robust 10-gene signature for OC prognosis prediction, which might be applied to assist clinical decision-making and individualized treatment.

Our results identified a robust 10-gene signature for OC prognosis prediction, which might be applied to assist clinical decision-making and individualized treatment.

To identify the association between phenolic chemicals and the risk of earlier puberty based on the available evidence by systematic review and meta-analysis.

Databases PubMed, Web of Science, and Cochrane Library were searched and retrieved appropriate journal articles on the association between phenols exposure and earlier puberty in children published before February 14, 2020. Stata software version 12.0 and Excel were used for statistical analysis.

Nine studies were included in the meta-analysis with total subjects of 4737. All the subjects included in our studies were girls. The pooled estimate has shown the association between 2, 5- dichrolophenol exposure, and earlier puberty in children with effect size (ES) 1.13 (95% CI 1.06, 1.20). Exposed to other types of phenolic chemicals such as bisphenol A, Triclosan, Benzophenone-3 were not statistically significant associated with the risk of earlier puberty in children with the overall pooled estimates of ES of 1.09 (95%CI 0.88, 1.35), ES 1.05(95% CI puberty in children. Future cohort studies should be conducted with more sample sizes to determine the relationship between 2, 5- dichlorophenol, and the risk of earlier puberty in children of all gender.Noise pollution is a major environmental problem due to its impact on human health and implications for other spheres of society. Since road traffic is the main source of noise pollution, the use of measurement methodologies to accurately determine the environmental noise levels to which the façades of buildings in cities are exposed is an important issue. This paper presents an experimental study in urban environments that uses different configurations to evaluate the influence of the position of the microphone and the parking lanes on the levels of road traffic noise to which the population is exposed. In urban settings in which sound waves propagate without obstacles between the lanes of traffic and the receivers, broadband results for the differences between noise levels measured by microphones placed at heights of 4.0 and 1.5 m showed a significant increase with an increase in the distance between the microphone and sound source of between -0.8 and 0.9 dBA over a range from 2 to 8 m. This difference between the two microphones was greater at points where a lane of parked vehicles was located between the road traffic lanes and the receivers were placed near the façades of building. At the same heights, the broadband difference in sound levels ranged from 2.7 to 4.5 dBA. This acoustic shielding effect due to the presence of parked vehicles started to be relevant in the 250 Hz band and increased progressively with frequency. Taking into account these experimental results and the recommendations in the European Noise Directive, it would be important to apply corrections to sound indicators for road traffic noise that are related to the height of the microphone. Making a distinction between urban configurations with and without lines of parked vehicles between the microphone and the road traffic lanes would be advisable.

Prenatal exposure to organophosphate (OP) pesticides associate with impaired neurodevelopment in humans and animal models. However, much uncertainty exists about the brain structural alterations underlying these associations. The objective of this study was to determine whether maternal OP pesticide metabolite concentrations in urine repeatedly measured during gestation are associated with brain morphology and white matter microstructure in 518 preadolescents aged 9-12 years.

Data came from 518 mother-child pairs participating in the Generation R Study, a population-based birth cohort from Rotterdam, the Netherlands. Maternal urine concentrations were determined for 6 dialkylphosphates (DAPs) including 3 dimethyl (DM) and 3 diethyl (DE) alkyl phosphate metabolites, collected at early, mid, and late pregnancy. At child's age 9-12 years, magnetic resonance imaging was performed to obtain T1-weighted images for brain volumes and surface-based cortical thickness and corticalsurface area, and diffusion tensor sequences for normal neurodevelopment. No associations were observed with structural brain morphology, including brain volumes, cortical thickness, and cortical surface area.The objective of this study is to evaluate comparatively the odor removal efficacy of two biofilters operated under different conditions and to identify taxonomically the microbial communities responsible for butyric acid degradation. Both biofiltration systems, which were filled with non-inoculated wood chips and exposed to gas streams containing butyric acid, were evaluated under different operational conditions (gas airflow and temperature) from the physical-chemical, microbiological and olfactometric points of view. The physical-chemical characterization showed the acidification of the packing material and the accumulation of butyric acid during the biofiltration process ( less then 60 days). The removal efficacy was found to be 98-100% during the first 20 days of operation, even at high odor concentration. Changes in the operational temperature increased the odor load factor from 400 to 1400 ouE/m2·s, which led to the reduction of microbiota in the packing material, and a drastic drop of the odor removal efficacy. However, the progressive increase in gas airflow improved the biodegradation efficacy of butyric acid up to 88% with odor loadings as high as 33,000 ouE/m3, while a linear relationship between odor inlet load and removal capacity was also found. The analysis of the microbial community showed that Proteobacteria was the most abundant phylum along the biofiltration time (58-92%) and regardless of the operational conditions. Finally, principal component analysis applied to the physical-chemical and microbiological data set revealed significant differences between the two biofilters under study.