α1-antitrypsin and its C-terminal fragment attenuate effects of degranulated neutrophil-conditioned medium on lung cancer HCC cells, in vitro

BACKGROUND: Tumor microenvironment, which is largely affected by inflammatory cells, is a crucial participant in the neoplastic process through promotion of cell proliferation, survival and migration. We measured the effects of polymorphonuclear neutrophil (PMN) conditioned medium alone, and supplemented with serine proteinase inhibitor α-1 antitrypsin (AAT) or its C-terminal fragment (C-36 peptide), on cultured lung cancer cells. METHODS: Lung cancer HCC cells were grown in a regular medium or in a PMN-conditioned medium in the presence or absence of AAT (0.5 mg/ml) or its C-36 peptide (0.06 mg/ml) for 24 h. Cell proliferation, invasiveness and release of IL-8 and VEGF were analyzed by [(3)H]-thymidine incorporation, Matrigel invasion and ELISA methods, respectively. RESULTS: Cells exposed to PMN-conditioned medium show decreased proliferation and IL-8 release by 3.9-fold, p < 0.001 and 1.3-fold, p < 0.05, respectively, and increased invasiveness by 2-fold (p < 0.001) compared to non-treated controls. In the presence of AAT, PMN-conditioned medium loses its effects on cell proliferation, invasiveness and IL-8 release, whereas VEGF is up-regulated by 3.7-fold (p < 0.001) compared to controls. Similarly, C-36 peptide abolishes the effects of PMN-conditioned medium on cell invasiveness, but does not alter its effects on cell proliferation, IL-8 and VEGF release. Direct HCC cell exposure to AAT enhances VEGF, but inhibits IL-8 release by 1.7-fold (p < 0.001) and 1.4-fold (p < 0.01) respectively, and reduces proliferation 2.5-fold (p < 0.01). In contrast, C-36 peptide alone did not affect these parameters, but inhibited cell invasiveness by 51.4% (p < 0.001), when compared with non-treated controls. CONCLUSIONS: Our data provide evidence that neutrophil derived factors decrease lung cancer HCC cell proliferation and IL-8 release, but increase cell invasiveness. These effects were found to be modulated by exogenously present serine proteinase inhibitor, AAT, and its C-terminal fragment, which points to a complexity of the relationships between tumor cell biological activities and local microenvironment

Thermography based inflammation monitoring of udder state in dairy cows: sensitivity and diagnostic priorities comparing with routine California mastitis test

Objectives of this study is to evaluate possibilities for early detection of udder’s diseases of Lithuanian Black and White cows and compare thermography and routine California mastitis test (CMT) results. Cows were examined in the negative and at positive ambient temperature. Infrared thermography (IRT) applied skin surface thermograms of teats in the area of Furstenberg’s rosette analyzed as posing evidence based signs of subclinical mastitis coincide with the CMT. It is shown, that subclinical inflammatory processes of cow’s mammary gland can be simply and successfully identified at an early stage of pathology development applying the thermal imaging method. IRT results measuring the skin surface temperature of teat sphincters of healthy dairy cows and cows with subclinical mastitis were completely similar to the CMT findings. Effectiveness of IRT does not depend from ambient conditions: inflammation can be easily detected both in positive and negative ambient temperatures. We confirm IRT being as alternative, noninvasive, high sensitive, rapid and portable method for subclinical various origins inflammatory processes of cow’s udder, which can be certified for practical subclinical mastitis screening and subsequent detection

Učinak dodatka Lactobacillus sakei na prinos mlijeka, lipidni profil i oksidativni status krava u laktaciji

The aim of the study was to investigate if feeding with Lactobacillus sakei could be beneficial for dairy cows. For this purpose, twenty mid-lactation cows were randomly allocated into two groups: the control, which received standard food, and the test group, which received standard food with L. sakei supplementation (5.0*108 colony forming units of L. sakei per day) for a two month period. Before and after the experimental period milk production and serum lipid profile (total cholesterol, high density lipoprotein cholesterol, and triglycerides) and oxidative markers (paraoxonase 1, total antioxidant capacity [TAC], total oxidant status [TOS], and oxidative stress index [OSI]) were evaluated. After the experimental period the control group showed very a mild, although significant decrease in serum triglycerides, while in the test group significant decreases in serum total cholesterol and TAC, and increases in triglycerides, TOS, and OSI were observed. The results of the present research indicate that L. sakei supplementation may not be beneficial for dairy cows, as alterations in lipid profile and increased oxidative stress were observed, without any increase in milk production.Cilj je ovog rada bio istražiti može li Lactobacillus sakei dodan u hranu poboljšati proizvodnju mlijeka u mliječnih krava. U tu je svrhu 20 krava u sredini laktacije nasumično bilo podijeljeno u dvije skupine: kontrolnu, koja je dobivala uobičajenu hranu i pokusnu, koja je dobivala uobičajenu hranu s dodatkom L. sakei (5,0x108 stanica L. sakei na dan). Pokus je trajao dva mjeseca. Prije i nakon pokusnog razdoblja promatrana je proizvodnja mlijeka i određivan lipidni profil (ukupni kolesterol, kolesterol visoke gustoće i trigliceridi) te oksidacijski biljezi (paraoksonaza 1, ukupni antioksidacijski kapacitet, ukupni oksidacijski status i indeks oksidacijskog stresa). Nakon pokusnog razdoblja kontrolna skupina pokazivala je blago, ali ipak signifikantno sniženje serumskih triglicerida, dok se u pokusne skupine značajno snizio ukupni kolesterol u serumu i ukupni antioksidacijski kapacitet, a povisili su se trigliceridi, vrijednosti ukupnog oksidacijskog statusa i indeks oksidacijskog stresa. Rezultati upućuju na zaključak da dodatak L. sakei nije bio od koristi za mliječne krave s obzirom na to da su bile ustanovljene promjene u lipidnom profilu i povišenje oksidacijskog stresa bez povećane proizvodnje mlijek

Programmed cell death 6 interacting protein (PDCD6IP) and Rabenosyn-5 (ZFYVE20) are potential urinary biomarkers for upper gastrointestinal cancer

PURPOSE: Cancer of the upper digestive tract (uGI) is a major contributor to cancer-related death worldwide. Due to a rise in occurrence, together with poor survival rates and a lack of diagnostic or prognostic clinical assays, there is a clear need to establish molecular biomarkers. EXPERIMENTAL DESIGN: Initial assessment was performed on urine samples from 60 control and 60 uGI cancer patients using MS to establish a peak pattern or fingerprint model, which was validated by a further set of 59 samples. RESULTS: We detected 86 cluster peaks by MS above frequency and detection thresholds. Statistical testing and model building resulted in a peak profiling model of five relevant peaks with 88% overall sensitivity and 91% specificity, and overall correctness of 90%. High-resolution MS of 40 samples in the 2-10 kDa range resulted in 646 identified proteins, and pattern matching identified four of the five model peaks within significant parameters, namely programmed cell death 6 interacting protein (PDCD6IP/Alix/AIP1), Rabenosyn-5 (ZFYVE20), protein S100A8, and protein S100A9, of which the first two were validated by Western blotting. CONCLUSIONS AND CLINICAL RELEVANCE: We demonstrate that MS analysis of human urine can identify lead biomarker candidates in uGI cancers, which makes this technique potentially useful in defining and consolidating biomarker patterns for uGI cancer screening

Thermography based inflammation monitoring of udder state in dairy cows: sensitivity and diagnostic priorities comparing with routine California mastitis test

Objectives of this study is to evaluate possibilities for early detection of udder’s diseases of Lithuanian Black and White cows and compare thermography and routine California mastitis test (CMT) results. Cows were examined in the negative and at positive ambient temperature. Infrared thermography (IRT) applied skin surface thermograms of teats in the area of Furstenberg’s rosette analyzed as posing evidence based signs of subclinical mastitis coincide with the CMT. It is shown, that subclinical inflammatory processes of cow’s mammary gland can be simply and successfully identified at an early stage of pathology development applying the thermal imaging method. IRT results measuring the skin surface temperature of teat sphincters of healthy dairy cows and cows with subclinical mastitis were completely similar to the CMT findings. Effectiveness of IRT does not depend from ambient conditions: inflammation can be easily detected both in positive and negative ambient temperatures. We confirm IRT being as alternative, noninvasive, high sensitive, rapid and portable method for subclinical various origins inflammatory processes of cow’s udder, which can be certified for practical subclinical mastitis screening and subsequent detection

Simvastatin inhibits TLR8 signaling in primary human monocytes and spontaneous TNF production from rheumatoid synovial membrane cultures

Simvastatin has been shown to have anti-inflammatory effects that are independent of its serum cholesterol lowering action, but the mechanisms by which these anti-inflammatory effects are mediated have not been elucidated. To explore the mechanism involved, the effect of simvastatin on Toll-like receptor (TLR) signalling in primary human monocytes was investigated. A short pre-treatment with simvastatin dose-dependently inhibited the production of tumor necrosis factor-α (TNF) in response to TLR8 (but not TLRs 2, 4, or 5) activation. Statins are known inhibitors of the cholesterol biosynthetic pathway, but intriguingly TLR8 inhibition could not be reversed by addition of mevalonate or geranylgeranyl pyrophosphate; downstream products of cholesterol biosynthesis. TLR8 signalling was examined in HEK 293 cells stably expressing TLR8, where simvastatin inhibited IKKα/β phosphorylation and subsequent NF-κB activation without affecting the pathway to AP-1. Since simvastatin has been reported to have anti-inflammatory effects in RA patients and TLR8 signalling contributes to TNF production in human RA synovial tissue in culture, simvastatin was tested in these cultures. Simvastatin significantly inhibited the spontaneous release of TNF in this model which was not reversed by mevalonate. Together, these results demonstrate a hitherto unrecognized mechanism of simvastatin inhibition of TLR8 signalling that may in part explain its beneficial anti-inflammatory effects

Thermography based inflammation monitoring of udder state in dairy cows: sensitivity and diagnostic priorities comparing with routine California mastitis test

Objectives of this study is to evaluate possibilities for early detection of udder’s diseases of Lithuanian Black and White cows and compare thermography and routine California mastitis test (CMT) results. Cows were examined in the negative and at positive ambient temperature. Infrared thermography (IRT) applied skin surface thermograms of teats in the area of Furstenberg’s rosette analyzed as posing evidence based signs of subclinical mastitis coincide with the CMT. It is shown, that subclinical inflammatory processes of cow’s mammary gland can be simply and successfully identified at an early stage of pathology development applying the thermal imaging method. IRT results measuring the skin surface temperature of teat sphincters of healthy dairy cows and cows with subclinical mastitis were completely similar to the CMT findings. Effectiveness of IRT does not depend from ambient conditions: inflammation can be easily detected both in positive and negative ambient temperatures. We confirm IRT being as alternative, noninvasive, high sensitive, rapid and portable method for subclinical various origins inflammatory processes of cow’s udder, which can be certified for practical subclinical mastitis screening and subsequent detection

European dog owner perceptions of obesity and factors associated with human and canine obesity

Abstract Obesity is a common nutrition-related disorder leading to reduced life expectancy in both humans and dogs. With the aim of identifying new prevention and control options, the study objectives were (1) to investigate dog-owner perceptions about obesity in terms of themselves and their dogs, and (2) to identify factors associated with obesity and possible social, environmental and economic drivers for its development in dog owners and their pets. A cross-sectional questionnaire-based study was performed across multiple countries. The questionnaire focused on human and canine obesity, associated factors and potential drivers, and was distributed online and in the form of hard copies among dog owners in 11 European countries. In total, 3,185 responses from ten countries were included in multivariable analyses. Between 19.1% and 48.8% of the dog owners reported to be overweight/obese. Owner-reported overweight/obesity in dogs ranged from 6.0% to 31.3% based on body condition score charts, and 31.8% to 69.4% based on body fat index charts. Common factors associated with obesity in owners and their dogs were age, gender and owners’ attitudes to diet and physical activity. Dog owners who did not consider obesity to be a disease were more likely to have obese dogs