Zobrazení zdroje stránky Forsythberntsen0205

BACKGROUND/OBJECTIVES The winter holiday season in the United States, which spans mid-November to mid-January, contributes to over half of annual body weight gain. Although self-reported data have linked this weight change to both increased energy intake and reduced physical activity, objective techniques have never been used; and thus, the actual cause of holiday weight gain is controversial. Here, we aimed to determine changes in components of energy balance leading to the holiday weight gain. METHODS Body weight change was compared between the pre-holiday (mid-September to mid-November) and the holiday period (mid-November to early January). Total energy expenditure (TEE) was measured using doubly labeled water during holiday time (early to mid-December). Subjective (ratings) and physiological (appetite-regulating hormones) measures of appetite, eating-away-from-home frequency, and incentive salience of food pictures were also evaluated. RESULTS In 23 obese adults (87% female), body weight change during the holidays (0.41 ± 0.42 kg) was significantly higher (P = 0.02) than the body weight change during the pre-holiday period (-0.86 ± 0.42 kg). TEE was unchanged during the two periods, suggesting no role of energy expenditure on weight gain. However, participants reported lower satisfaction after a meal pre-load which was significantly correlated with increased body weight during the holiday period. An increase in number of episodes of eating at sit-down restaurants was also reported during that period. Overall, these changing behaviors were supported by a non-significant increase in energy intake (+80 kcal/day, P = 0.07) observed during the study holiday period. CONCLUSION We conclude that a decrease in energy expenditure does not result in the weight increase, but that increase in food intake is the more likely cause. Our data imply that compromised internal satiety mechanisms in presence of external food cues and diet-related behavioral variables during the holidays may influence weight gain.BACKGROUND/OBJECTIVES Physical activity is beneficial to lipid profiles; however, the association between sedentary behavior and sleep and pediatric dyslipidemia remains unclear. We aimed to investigate whether sedentary behavior or sleep predicted lipid profiles in children over a 2-year period. SUBJECTS/METHODS Six hundered and thirty children from the QUALITY cohort, with at least one obese parent, were assessed prospectively at ages 8-10 and 10-12 years. Measures of sedentary behavior included self-reported TV viewing and computer/video game use. Seven-day accelerometry was used to derive sedentary behavior and sleep duration. Adiposity was assessed using DEXA scans. Twenty-four-hour dietary recalls yielded estimates of carbohydrate and fat intake. Outcomes included fasting total cholesterol, triglycerides, HDL and LDL-cholesterol. Multivariable models were adjusted for adiposity and diet. RESULTS At both Visit 1 (median age 9.6 year) and Visit 2 (median age 11.6 year), children were of normal weight (55%), overweight (22%), or obese (22%). Every additional hour of TV viewing at Visit 1 was associated with a 7.0% triglyceride increase (95% CI 3.5, 10.6; P  less then  0.01) and 2.6% HDL decrease (95% CI -4.2, -0.9; P  less then  0.01) at Visit 2; findings remained significant after adjusting for adiposity and diet. Every additional hour of sleep at Visit 1 predicted a 4.8% LDL decrease (95% CI -9.0, -0.5; P = 0.03) at Visit 2, after adjusting for fat intake; this association became nonsignificant once controlling for adiposity. CONCLUSIONS Longer screen time during childhood appears to deteriorate lipid profiles in early adolescence, even after accounting for other major lifestyle habits. There is preliminary evidence of a deleterious effect of shorter sleep duration, which should be considered in further studies.Limited therapeutic options are available for advanced-stage hepatocellular carcinoma owing to its poor diagnosis. Drug resistance to sorafenib, the only available targeted agent, is commonly reported. The comprehensive elucidation of the mechanisms underlying sorafenib resistance may thus aid in the development of more efficacious therapeutic agents. To clarify the signaling changes contributing to resistance, we applied quantitative phosphoproteomics to analyze the differential phosphorylation changes between parental and sorafenib-resistant HuH-7 cells. Consequently, an average of ~1500 differential phosphoproteins were identified and quantified, among which 533 were significantly upregulated in resistant cells. Further bioinformatic integration via functional categorization annotation, pathway enrichment and interaction linkage analysis led to the discovery of alterations in pathways associated with cell adhesion and motility, cell survival and cell growth and the identification of a novel target, EphA2, in resistant HuH-7R cells. In vitro functional analysis indicated that the suppression of EphA2 function impairs cell proliferation and motility and, most importantly, overcomes sorafenib resistance. The attenuation of sorafenib resistance may be achieved prior to its development through the modulation of EphA2 and the subsequent inhibition of Akt activity. Binding analyses and in silico modeling revealed a ligand mimic lead compound, prazosin, that could abate the ligand-independent oncogenic activity of EphA2. [https://www.selleckchem.com/ click here] Finally, data obtained from in vivo animal models verified that the simultaneous inhibition of EphA2 with sorafenib treatment can effectively overcome sorafenib resistance and extend the projected survival of resistant tumor-bearing mice. Thus our findings regarding the targeting of EphA2 may provide an effective approach for overcoming sorafenib resistance and may contribute to the management of advanced hepatocellular carcinoma.Protein disulfide isomerase (PDI) participates in the pathogenesis of numerous diseases. Increasing evidence indicates that intravascular cell-derived PDI plays an important role in the initiation and progression of cardiovascular diseases, including thrombosis and vascular inflammation. Recent studies with PDI conditional knockout mice have advanced our understanding of the function of cell-specific PDI in disease processes. Furthermore, the identification and development of novel small-molecule PDI inhibitors has led into a new era of PDI research that transitioned from the bench to bedside. In this review, we will discuss recent findings on the regulatory role of PDI in cardiovascular disease.Ultrafine particles (UFPs) are aerosols with an aerodynamic diameter of 0.1 µm (100 nm) or less. link2 There is a growing concern in the public health community about the contribution of UFPs to human health. Despite their modest mass and size, they dominate in terms of the number of particles in the ambient air. A particular concern about UFPs is their ability to reach the most distal lung regions (alveoli) and circumvent primary airway defenses. Moreover, UFPs have a high surface area and a capacity to adsorb a substantial amount of toxic organic compounds. Harmful systemic health effects of PM10 or PM2.5 are often attributable to the UFP fraction. In this review, we examine the physicochemical characteristics of UFPs to enable a better understanding of the effects of these particles on human health. The characteristics of UFPs from diesel combustion will be discussed in the greatest detail because road vehicles are the primary source of UFP emissions in urban pollution hotspots. Finally, we will elaborate on the role of UFPs on global climate change, since the adverse effects of UFPs on meteorological processes and the hydrological cycle may even be more harmful to human health than their direct toxic effects.Ultrafine particles (PM0.1), which are present in the air in large numbers, pose a health risk. They generally enter the body through the lungs but translocate to essentially all organs. Compared to fine particles (PM2.5), they cause more pulmonary inflammation and are retained longer in the lung. Their toxicity is increased with smaller size, larger surface area, adsorbed surface material, and the physical characteristics of the particles. Exposure to PM0.1 induces cough and worsens asthma. Metal fume fever is a systemic disease of lung inflammation most likely caused by PM0.1. The disease is manifested by systemic symptoms hours after exposure to metal fumes, usually through welding. PM0.1 cause systemic inflammation, endothelial dysfunction, and coagulation changes that predispose individuals to ischemic cardiovascular disease and hypertension. PM0.1 are also linked to diabetes and cancer. PM0.1 can travel up the olfactory nerves to the brain and cause cerebral and autonomic dysfunction. Moreover, in utero exposure increases the risk of low birthweight. link3 Although exposure is commonly attributed to traffic exhaust, monitored students in Ghana showed the highest exposures in a home near a trash burning site, in a bedroom with burning coils employed to abate mosquitos, in a home of an adult smoker, and in home kitchens during domestic cooking. The high point-source production and rapid redistribution make incidental exposure common, confound general population studies and are compounded by the lack of global standards and national reporting. The potential for PM0.1 to cause harm to health is great, but their precise role in many illnesses is still unknown and calls for more research.The relationship between ambient particulate matter exposure and health has been well established. Ultrafine particles (UFP) with a diameter of 100 nm or less are known to increase pulmonary disease risk. Biological factors in dust containing UFP can cause severe inflammatory reactions. Pulmonary diseases develop primarily as a result of chronic inflammation caused by immune dysfunction. Thus, this review focuses on the adverse pulmonary effects of biological UFP, principally lipopolysaccharide (LPS), and bacterial extracellular vesicles (EVs), in indoor dust and the pathophysiological mechanisms involved in the development of chronic pulmonary diseases. The impact of LPS-induced pulmonary inflammation is based primarily on the amount of inhaled LPS. When relatively low levels of LPS are inhaled, a cascade of immune responses leads to Th2 cell induction, and IL-5 and IL-13 released by Th2 cells contributes to asthma development. Conversely, exposure to high levels of LPS induces a Th17 cell response, leading to increased production of IL-17, which is associated with asthma, COPD, and lung cancer incidence. Responses to bacterial EV exposure can similarly be broadly divided based on whether one of two mechanisms, either intracellular or extracellular, is activated, which depends on the type of the parent cell. Extracellular bacteria-derived EVs can cause neutrophilic inflammation via Th17 cell induction, which is associated with asthma, emphysema, COPD, and lung cancer. On the other hand, intracellular bacteria-derived EVs lead to mononuclear inflammation via Th1 cell induction, which increases the risk of emphysema. In conclusion, future measures should focus on the overall reduction of LPS sources in addition to the improvement of the balance of inhaled bacterial EVs in the indoor environment to minimize pulmonary disease risk.