The initiation of intestinal inflammation involves complex intercellular cross-talk of inflammatory cells, including the epithelial and immune cells, and the gut microbiome. This multicellular ...complexity has hampered the identification of the trigger that orchestrates the onset of intestinal inflammation. To identify the initiator of inflammatory host–microbiome cross-talk, we leveraged a pathomimetic “gut inflammation-on-a-chip” undergoing physiological flow and motions that recapitulates the pathophysiology of dextran sodium sulfate (DSS)-induced inflammation in murine models. DSS treatment significantly impaired, without cytotoxic damage, epithelial barrier integrity, villous microarchitecture, and mucus production, which were rapidly recovered after cessation of DSS treatment. We found that the direct contact of DSS-sensitized epithelium and immune cells elevates oxidative stress, in which the luminal microbial stimulation elicited the production of inflammatory cytokines and immune cell recruitment. In contrast, an intact intestinal barrier successfully suppressed oxidative stress and inflammatory cytokine production against the physiological level of lipopolysaccharide or nonpathogenic Escherichia coli in the presence of immune elements. Probiotic treatment effectively reduced the oxidative stress, but it failed to ameliorate the epithelial barrier dysfunction and proinflammatory response when the probiotic administration happened after the DSS-induced barrier disruption. Maintenance of epithelial barrier function was necessary and sufficient to control the physiological oxidative stress and proinflammatory cascades, suggesting that “good fences make good neighbors.” Thus, the modular gut inflammation-on-a-chip identifies the mechanistic contribution of barrier dysfunction mediated by intercellular host–microbiome cross-talk to the onset of intestinal inflammation.
Transitional cell carcinoma (TCC) is the most common malignant tumor of the canine urinary tract and tends to have a poor prognosis due to its invasive potential. Recent studies have reported that up ...to 80% of canine urothelial carcinoma has the BRAF V595E mutation, which is homologous to the human V600E mutation. Activating the BRAF mutation is an actionable target for developing effective therapeutic agents inhibiting the BRAF/mitogen-activated protein kinase (MAPK) pathway in canine cancer as well as human cancer. We established novel canine TCC cell lines from two tumor tissues and one metastatic lymph node of canine TCC patients harboring the BRAF V595E mutation. Tumor tissues highly expressed the BRAF mutant and phosphorylated extracellular signal-related kinases (ERK)1/2 proteins. The derived cell lines demonstrated activated MAPK pathways. We also evaluated the cell lines for sensitivity to BRAF inhibitors. Sorafenib, a multiple kinase inhibitor targeting RAF/vascular endothelial growth factor receptor (VEGFR), successfully inhibited the BRAF/MAPK pathway and induced apoptosis. The established canine TCC cell lines responded with greater sensitivity to sorafenib than to vemurafenib, which is known as a specific BRAF inhibitor in human cancer. Our results demonstrated that canine TCC cells showed different responses compared to human cancer with the BRAF V600E mutation. These cell lines would be valuable research materials to develop therapeutic strategies for canine TCC patients.
The present study examines two possible routes lonely people can take to alleviate their loneliness: One route via escape motivation and smartphone-mediated communication vs. another route via ...relationship motivation and face-to-face interaction. Two hypothesized path models were tested with a total of 930 U.S. American participants who were nationally recruited through a professional survey company. Those with a high level of loneliness tend to rely more on smartphone-mediated communication, while being reluctant to engage in face-to-face interaction. Such combination of the two increases the possibility of developing problematic use of smartphone but decreases perceived social support from their social networks. Furthermore, a multi-group analysis suggested that young adults of age 31–40 would develop problematic use of smartphone more than adolescents of age 13–18.
•Examined two possible routes lonely people can take to alleviate their loneliness.•Lonely people rely on smartphone while not much on face-to-face interaction.•Young adults might develop problems with smartphone more than teenagers.
Previous studies have identified microplastics (MPs) in commercial table salts but could not exactly address the origin of the MPs because of several limitations. The present study is based on the ...hypothesis that commercial sea salts can act as an indicator of MP pollution in the surrounding environment unless the MPs are filtered out during the manufacturing process. A total of 39 different salt brands produced at geospatially different sites, including 28 sea salt brands from 16 countries/regions on six continents, were investigated. A wide range of MP content (in number of MPs per kg of salt; n/kg) was found: 0–1674 n/kg (excluding one outlier of 13 629 n/kg) in sea salts, 0–148 n/kg in rock salt, and 28–462 n/kg in lake salt. Relatively high MP content was identified in sea salts produced in Asian countries/regions. The abundance of MPs in unrefined sea salts (n = 25) exhibited significant linear correlations with plastic emissions from worldwide rivers (r 2= 0.33; p = 0.003) and with the MP pollution levels in surrounding seawater (r 2= 0.46; p = 0.021) in the published literature. The results indicate that not only is Asia a hot spot of global plastic pollution, as previous studies have suggested, but also that sea salt can be a good indicator of the magnitude of MP pollution in the surrounding marine environment.
Obesity and metabolic syndrome (MetS) are associated with high risk of cardiac dysfunction and heart failure. We assessed the effect of obesity and metabolic health status on left ventricular (LV) ...structure and function in subjects without overt heart disease.
In 789 subjects (58.8±13.0 years, 50.7% males) without overt heart disease, LV morphology and function were compared among 6 groups stratified by body mass index (BMI) (normal weight, overweight and obese) and metabolic health status (meeting ≤1 criterion of MetS excluding waist circumference defined as metabolically healthy; otherwise, metabolically unhealthy).
LV ejection fraction (LVEF) was not different among the 6 groups (P>0.05). However, high BMI and poor metabolic health were associated with poorer global longitudinal strain (GLS), higher LV mass index (LVMI) and higher E/e' (P<0.001). Poor metabolic health status was associated with greater adverse changes in LV structure and function than obesity, and among MetS components, high systolic blood pressure (SBP) showed the greatest impact. Higher SBP, BMI and triglycerides were independently associated with worse GLS, and higher SBP was also associated with worse LVMI and E/e´. GLS, LVMI and E/e´ worsened in proportion to the number of MetS criteria or continuous MetS scores. Adverse myocardial changes associated with obesity were significant in the metabolically healthy group, but not in the metabolically unhealthy group.
Obesity and poor metabolic health status were associated with subclinical decrement in LV systolic and diastolic function, and higher LV mass, but not with LVEF, in subjects without overt heart disease.
Silicon monoxide (SiO), similar to its more common counterpart silicon (Si), is considered as an attracting anode material for advanced Li-ion batteries (LiBs) due to its high theoretical capacity. ...However, many electrochemical properties of SiO have not been explored as much as those of Si. In this study, we report fundamental properties of SiO as an anode material, which offer promising LiB performances superior to pure Si anodes. The Li-ion diffusion in SiO was found to be consistently faster than that in Si, as evidenced by galvanostatic intermittent titration technique (GITT) and electrochemical impedance spectroscopy (EIS). As a result, SiO anodes can deliver much improved fast charging/discharging capability compared with pure Si anodes, which indicates that SiO is a better candidate for high-power cell applications. The volume expansion rate of SiO particles was determined to be ∼118% by using scanning electron microscopy (SEM)-based particle size distribution (PSD) analysis, which is less than half of that of Si particles (c.a. 280%). Meanwhile, the open circuit potential (OCP) of SiO was found to be very close to Si, except near the end of delithiation state. These results provide fundamental information on SiO for its future applications as the next generation LiB anodes.
•Li-ion diffusion in SiO is faster than Si as evidenced by GITT and EIS experiments.•SiO anodes outperform Si anodes during fast-charging and fast-discharging.•OCP measured by GITT exhibits lower hysteresis than that by C/50-rate cycling.•PSD data showed a low volume expansion (∼118%) of SiO compared with Si.•As a result, SiO is a better candidate for high-power cell applications.
Mitochondrial ribosomes in cancer Kim, Hyun-Jung; Maiti, Priyanka; Barrientos, Antoni
Seminars in cancer biology,
12/2017, Letnik:
47
Journal Article
Recenzirano
Odprti dostop
Abstract Mitochondria play fundamental roles in the regulation of life and death of eukaryotic cells. They mediate aerobic energy conversion through the oxidative phosphorylation (OXPHOS) system, and ...harbor and control the intrinsic pathway of apoptosis. As a descendant of a bacterial endosymbiont, mitochondria retain a vestige of their original genome (mtDNA), and its corresponding full gene expression machinery. Proteins encoded in the mtDNA, all components of the multimeric OXPHOS enzymes, are synthesized in specialized mitochondrial ribosomes (mitoribosomes). Mitoribosomes are therefore essential in the regulation of cellular respiration. Additionally, an increasing body of literature has been reporting an alternative role for several mitochondrial ribosomal proteins as apoptosis-inducing factors. No surprisingly, the expression of genes encoding for mitoribosomal proteins, mitoribosome assembly factors and mitochondrial translation factors is modified in numerous cancers, a trait that has been linked to tumorigenesis and metastasis. In this article, we will review the current knowledge regarding the dual function of mitoribosome components in protein synthesis and apoptosis and their association with cancer susceptibility and development. We will also highlight recent developments in targeting mitochondrial ribosomes for the treatment of cancer.
To develop a practical thyroid imaging reporting and data system (TIRADS) with which to categorize thyroid nodules and stratify their malignant risk.
The institutional review board approved this ...retrospective study, and the requirement to obtain informed consent for the review of images and records was waived. From May to December 2008, ultrasonographically (US)-guided fine-needle aspiration biopsy (FNAB) was performed in 3674 focal thyroid nodules in 3414 consecutive patients. The study included the 1658 thyroid nodules (≥1 cm in maximum diameter at US) in 1638 patients (1373 women, 265 men) for which pathologic diagnosis or follow-up findings were available. Univariate and multivariate analyses with generalized estimating equations were performed to investigate the relationship between suspicious US features and thyroid cancer. A score for each significant factor was assigned and multiplied by the β coefficient obtained for each significant factor from multivariate logistic regression analysis. Scores for each significant factor were then added, resulting in an equation that fitted the probability of malignancy in thyroid nodules. The authors evaluated the fitted probability by using a regression equation; the risk of malignancy was determined according to the number of suspicious US features.
The following US features showed a significant association with malignancy: solid component, hypoechogenicity, marked hypoechogenicity, microlobulated or irregular margins, microcalcifications, and taller-than-wide shape. As the number of suspicious US features increased, the fitted probability and risk of malignancy also increased. Positive predictive values according to the number of suspicious US features were significantly different (P < .001).
Risk stratification of thyroid malignancy by using the number of suspicious US features allows for a practical and convenient TIRADS.
This study investigated bioaccumulation and toxicity derived from heavy metals in laying hens. The 160 52-week old laying hens were divided into 5 treatments with 8 replicates of 4 birds per pen. The ...treatments consisted of the control diet (without heavy metals), control diet with half the available dosage (AD, 5 ppm lead and 0.2 ppm mercury), AD (10 ppm lead and 0.4 ppm mercury), 2-fold AD (20 ppm lead and 0.8 ppm mercury), and 3-fold AD (30 ppm lead and 1.2 ppm mercury), and were provided to the laying hens for 8 weeks. Food and water were provided on an ad libitum basis at all times. Body weight and food intake were recorded once every two weeks, and eggs were collected and recorded daily. Two birds from each pen were euthanized to collect blood and organ samples on week 4 and 8. The 3-fold AD diet reduced food intake compared to that of the control and AD diets (P<0.05). Hens fed the half AD diet had darker yolk compared to those fed the control and AD diet on week 4 (P<0.05). Hens fed the 2- and 3-fold AD diets had increased relative liver weight, blood glutamic pyruvic transaminase and glutamic oxaloacetic transaminase levels (P<0.05), while F1 follicle weights decreased on week 4 and 8. No difference was found in egg production rate, egg quality, ovarian follicle, blood metabolites including protein, globulin, albumin, and urea nitrogen throughout the study (P>0.05). Heavy metal concentrations in the liver, eggs, and feathers were not detected at both week 4 and 8. Our results indicate that in-feed heavy metals for layer diets up to 30 ppm of lead and 1.2 ppm of mercury brought on hepatic dysfunction increasing blood metabolites that are associated with liver inflammation.
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