Kaempferol protects against streptozotocin-induced diabetic cardiomyopathy in rats by a hypoglycemic effect and upregulating SIRT1.

This study investigated if kaempferol could attenuate the oxidative, inflammatory, and fibrotic damage of the left ventricles (LVs) in streptozotocin (STZ)-diabetic rats by modulating silent mating type information regulation 2 homolog 1 (SIRT1) signaling. Adult male rats were divided into 5 groups (n = 12/each) as control, control + kaempferol, STZ-induced diabetes mellitus (STZ-DM), STZ-DM + kaempferol, and STZ-DM + kaempferol + EX-527, a sirtuin 1 (SIRT1) inhibitor. Administration of kaempferol to diabetic rats significantly preserved the systolic and diastolic functions of the LVs that was associated with a significant reduction in ventricular collagen deposition, infiltration of inflammatory cells, and protein expression of Bcl2-associated X protein (Bax), cleaved caspase-3, and cytochrome-C. In both the control and diabetic rats, kaempferol attenuated the loss in body weights, reduced fasting glucose levels, and increased fasting insulin levels and HOMA-ß. Besides, kaempferol lowered the levels of reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), downregulated the transforming growth factor-ß1 (TGF-ß1) and reduced the nuclear levels of NF-κB p65. In concomitant, kaempferol increased the LV levels of manganese superoxide dismutase (MnSOD) and glutathione (GSH) and stimulated the total protein levels of Bcl2, the nuclear activity of SIRT1, and nuclear levels of nuclear factor erythroid 2-related factor 2 (Nrf2). These events were associated with increased deacetylase activity and total levels of SIRT1 and a parallel decrease in the acetylation of Nrf2, NF-κB, smad2, and FOXO1. In conclusion: kaempferol attenuate diabetic cardiomyopathy in STZ-treated rats through its hypoglycaemic and insulin-releasing effects, as well as a cardiac independent mechanism that involves activation of SIRT1.

The potential of using climate indices as powerful tools to explain mortality anomalies: An application to mainland Spain.

Changes in the frequency and magnitude of extreme weather events represent one of the key indicators of climate change and variability. These events can have an important impact on mortality rates, especially in the ageing population. This study assessed the spatial and seasonal distributions of mortality rates in mainland Spain and their association with climatic conditions over the period 1979-2016. The analysis was done on a seasonal and annual basis using 79 climatic indices and regional natural deaths data. Results indicate large spatial variability of natural deaths, which is mostly related to how the share of the elderly in the population varied across the studied regions. Spatially, both the highest mortality rates and the largest percentage of elders were found in the northwest areas of the study domain, where an extreme climate prevails, with very cold winters and hot summers. A strong seasonality effect was observed, winter shows more than 10% of natural deaths compared to the rest of the seasons. Also, results suggest a strong relation between climatic indices and natural deaths, albeit with a high spatial and seasonal variability. Climatic indices and natural deaths show a stronger correlation in winter and summer than in spring and autumn.

The complex multi-sectoral impacts of drought: Evidence from a mountainous basin in the Central Spanish Pyrenees.

We analyzed the impacts of drought severity on a variety of sectors in a topographically complex basin (the upper Aragón basin 2181 km2) in the Central Spanish Pyrenees. Using diverse data sources including meteorological and hydrological observations, remote sensing and tree rings, we analyze the possible hydrological implications of drought occurrence and severity on water availability in various sectors, including downstream impacts on irrigation water supply for crop production. Results suggest varying responses in forest activity, secondary growth, plant phenology, and crop yield to drought impacts. Specifically, meteorological droughts have distinct impacts downstream, mainly due to water partitioning between streamflow and irrigation channels that transport water to crop producing areas. This implies that drought severity can extend beyond the physical boundaries of the basin, with impacts on crop productivity. This complex response to drought impacts makes it difficult to develop objective basin-scale operational definitions for monitoring drought severity. Moreover, given the high spatial variability in responses to drought across sectors, it is difficult to establish reliable drought thresholds from indices that are relevant across all socio-economic sectors. The anthropogenic impacts (e.g. water regulation projects, ecosystem services, land cover and land use changes) pose further challenges to assessing the response of different systems to drought severity. This study stresses the need to consider the seasonality of drought impacts and appropriate drought time scales to adequately assess and understand their complexity.

Dehydroepiandrosterone protects against acetaminophen-induced liver damage in rats by upregulation of Bcl-2 and activation of sirt signalling.

The study examined the protective effect of exogenous administration of dehydroepiandrosterone (DHEA) against acetaminophen (APAP) -induced liver damage in rats and tested the underlying mechanism(s). Male rats were divided into 5 groups as control, control + DHEA, APAP, APAP + DHEA, and APAP + DHEA + EX-527 (SIRT1 inhibitor). Treatments were conducted for 10 days and then followed by intragastric administration of a single dose of APAP. DHEA not only reduced serum alanine transaminase (ALT) and aspartate aminotransferase (AST) but also preserved the liver structures. Besides, DHEA reduced hepatic levels of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), Bax, cleaved caspase-3. In the livers of both the control and APAP-treated rats, DHEA suppressed the generation of reactive oxygen species (ROS) and malondialdehyde (MDA), increased levels of glutathione (GSH), MnSOD (SOD2), and Bcl-2 levels, lowered Bax/Bcl-2 ratio, enhanced the activity of nuclear factor erythroid-derived 2-like 2 (Nrf2), and inhibited nuclear factor kappaB (NF-κB) p65. All these effects coincided with a significant increase in the levels and activity of SIRT1 and a reduction in the acetylation of Nrf2, p53, forkhead box class O transcription factor 1 (FOXO1), and NF-κB p65. Except for Bcl-2, treating the rats with EX-527 abolished the beneficial effects of DHEA on all these markers. In conclusion, DHEA prevents APAP-induced liver damage by concomitant upregulation of Bcl-2 and SIRT1-dependent effect.

Knowledge about sources of dietary fibres and health effects using a validated scale: a cross-country study.

OBJECTIVES: Dietary fibre (DF) is one of the components of diet that strongly contributes to health improvements, particularly on the gastrointestinal system. Hence, this work intended to evaluate the relations between some sociodemographic variables such as age, gender, level of education, living environment or country on the levels of knowledge about dietary fibre (KADF), its sources and its effects on human health, using a validated scale. STUDY DESIGN: The present study was a cross-sectional study. METHODS: A methodological study was conducted with 6010 participants, residing in 10 countries from different continents (Europe, America, Africa). The instrument was a questionnaire of self-response, aimed at collecting information on knowledge about food fibres. The instrument was used to validate a scale (KADF) which model was used in the present work to identify the best predictors of knowledge. The statistical tools used were as follows: basic descriptive statistics, decision trees, inferential analysis (t-test for independent samples with Levene test and one-way ANOVA with multiple comparisons post hoc tests). RESULTS: The results showed that the best predictor for the three types of knowledge evaluated (about DF, about its sources and about its effects on human health) was always the country, meaning that the social, cultural and/or political conditions greatly determine the level of knowledge. On the other hand, the tests also showed that statistically significant differences were encountered regarding the three types of knowledge for all sociodemographic variables evaluated: age, gender, level of education, living environment and country. CONCLUSIONS: The results showed that to improve the level of knowledge the actions planned should not be delineated in general as to reach all sectors of the populations, and that in addressing different people, different methodologies must be designed so as to provide an effective health education.

Knowledge about dietary fibres (KADF): development and validation of an evaluation instrument through structural equation modelling (SEM).

OBJECTIVES: Because there is scientific evidence that an appropriate intake of dietary fibre should be part of a healthy diet, given its importance in promoting health, the present study aimed to develop and validate an instrument to evaluate the knowledge of the general population about dietary fibres. STUDY DESIGN: The present study was a cross sectional study. METHODS: The methodological study of psychometric validation was conducted with 6010 participants, residing in 10 countries from three continents. The instrument is a questionnaire of self-response, aimed at collecting information on knowledge about food fibres. Exploratory factor analysis (EFA) was chosen as the analysis of the main components using varimax orthogonal rotation and eigenvalues greater than 1. In confirmatory factor analysis by structural equation modelling (SEM) was considered the covariance matrix and adopted the maximum likelihood estimation algorithm for parameter estimation. RESULTS: Exploratory factor analysis retained two factors. The first was called dietary fibre and promotion of health (DFPH) and included seven questions that explained 33.94% of total variance (α = 0.852). The second was named sources of dietary fibre (SDF) and included four questions that explained 22.46% of total variance (α = 0.786). The model was tested by SEM giving a final solution with four questions in each factor. This model showed a very good fit in practically all the indexes considered, except for the ratio χ(2)/df. The values of average variance extracted (0.458 and 0.483) demonstrate the existence of convergent validity; the results also prove the existence of discriminant validity of the factors (r(2) = 0.028) and finally good internal consistency was confirmed by the values of composite reliability (0.854 and 0.787). CONCLUSIONS: This study allowed validating the KADF scale, increasing the degree of confidence in the information obtained through this instrument in this and in future studies.

G-Protein-Coupled Chemokine Receptor Gene in Lumpy Skin Disease Virus Isolates from Cattle and Water Buffalo (Bubalus bubalis) in Egypt.

Lumpy skin disease virus (LSDV), sheep poxvirus (SPV) and goat poxvirus (GPV) are the most serious poxviruses of ruminants. In this study, we analysed the G-protein-coupled chemokine receptor (GPCR) genes of LSDV isolates from cattle and water buffalo (Bubalus bubalis) in Egypt during the summer of 2011. Multiple alignments of the nucleotide sequences revealed that the water buffalo LSDV isolate differed from the cattle isolate at four nucleotide positions, and both isolates had nine nucleotide mutations from the reference strain, Egyptian tissue culture-adapted cattle LSDV/Ismailyia88 strain. Compared with the GPCR sequences of SPV and GPV strains, a 21 nucleotide insertion and a 12 nucleotide deletion were identified in the GPCR genes of our used isolates and other LSDVs. The amino acid sequences of GPCR genes of our isolates contained the unique signature of LSDV (A11 , T12 , T34 , S99 and P199 ). Phylogenetic analyses showed that the GPCR genes of cattle and water buffalo LSDVs were closest genetically, indicating a potential transmission of cattle LSDV to water buffalo.

Sequence analysis of attachment gene of lumpy skin disease and sheep poxviruses.

In Egypt, protection of cattle against lumpy skin disease (LSD) was carried out using a sheep poxvirus (Kenyan strain) vaccination strategy. In the present study 15 skin nodules from LSD suspected cows and 5 scab samples from sheep pox (SP) suspected sheep were collected. Hyperimmune rabbit sera to Lumpy skin disease virus (LSDV)/Ismailyia88 strain and sheep pox virus (SPV)/ Kenyan vaccinal strain were prepared. The causative agent in the collected samples was identified using immunoflourescence (IF) and immunoperoxidase techniques. Of the 15 skin nodules suspected of LSD, 10 showed a positive reaction and 3 out of 5 skin scabs suspected of sheeppox were found to be positive. An antigenic correlation between field skin isolate of LSDV, tissue culture adapted LSDV/Ismailyia88 strain, field skin isolate of SPV and SPV/Kenyan vaccinal strain was studied using prepared hyperimmune sera. Also, nucleotide sequence of the PCR amplified attachment gene fragments of field skin isolate of LSDV, tissue culture adapted LSDV/Ismailyia88 strain, field skin isolate of SPV and SPV /Kenyan vaccinal strain were compared. The results revealed that the four used viruses were antigenically identical. Sequence analysis indicated that field skin LSDV isolate is more related to tissue culture adapted LSDV/Ismailyia88 strain than to vaccinal SPV/ Kenyan strain and the skin isolate of SPV is more closely related to field skin isolate of LSDV than to SPV/Kenyan vaccinal strain. Thus, further study should be applied on the advantage of a LSD vaccine prepared from LSDV in protection of cattle against LSD compared to the commonly used sheep pox vaccine.

Comparative analysis of the sialic acid binding activity and the tropism for the respiratory epithelium of four different strains of avian infectious bronchitis virus.

Avian infectious bronchitis virus (IBV) is a major pathogen in commercial poultry flocks. We recently demonstrated that sialic acid serves as a receptor determinant for IBV on the tracheal epithelium. Here we compared the IBV strains Beaudette, 4/91, Italy02, and QX for their sialic acid-binding properties. We demonstrate that sialic acid binding is important for the infection of primary chicken kidney cells and the tracheal epithelium by all four strains. There were only slight differences between the four strains, indicating the universal usage of sialic acids as receptor determinants by IBV. In addition, we analysed the primary target cells in the respiratory epithelium of the four different strains and found that all of them infected ciliated cells and goblet cells.

Heat shock protein expression independently predicts survival outcome in schistosomiasis-associated urinary bladder cancer.

BACKGROUND: Heat shock proteins (HSPs) are synthesized by cells in response to various stress conditions, including carcinogenesis. These molecules have been studied in several malignancies, among which bladder carcinoma. This is the first study attempting to clarify the significance of HSP27 and HSP70 in schistosomiasis-associated bladder carcinoma and their relation to prognosis. METHODS: HSP27 and HSP70 were localized immunohistochemically in tissue sections from 75 chistosomiasis-associated bladder carcinomas. Their expression was correlated with clinical and pathological features and their impact on 5-year disease-free survival was studied with univariate and multivariate analysis. RESULTS: In all, 45 and 51 patients were positive for HSP27 and HSP70 expression, respectively. A significant correlation was found between expression of both HSPs and tumor grade, stage, DNA ploidy and recurrence. In univariate analysis, a statistically significant association of HSP27 and HSP70 expression with 5-year disease-free survival was found. In a multivariate Cox proportional hazards model, both HSP27 and HSP70 maintained a statistically significant impact on survival. CONCLUSIONS: The current results indicate that expression of HSP27 and HSP70 may have prognostic relevance in patients with schistosomiasis-associated bladder cancer. HSPs may be useful markers for patients with this type of bladder carcinoma and may be used for predicting disease progression.

Prognostic value of carcinoma-associated antigen MK-1 in urinary bladder carcinoma.

BACKGROUND: The present study has been performed to evaluate the expression of MK-1 in schistosomiasis-associated squamous cell carcinoma of the urinary bladder and to correlate this new marker with the conventional histopathological parameters. PATIENTS AND METHODS: Paraffin sections of 5-microm thickness from 81 cases were prepared for hematoxylin and eosin staining and immunohistochemical analysis of MK-1 expression was carried out. RESULTS: Forty-six cases (56.8%) were positive for MK-1 protein expression. Significant correlations between MK-1 expression and tumor grade (p=0.004), schistosoma (p=0.031), DNA ploidy (p=0.001), and tumor recurrence (p<0.001) were observed. MK-1, sex, tumor grade, stage, schistosoma, DNA ploidy, and recurrence were evaluated in relation to outcome. Univariate and multivariate analysis of survival were performed. The overall 5-year survival was 51.85%. In univariate analysis, MK-1 expression, tumor grade, DNA ploidy, and recurrence had a significant impact on the survival of these patients. In a Cox proportional hazards model, recurrence maintained its significant impact on survival. CONCLUSIONS: These findings suggest that MK-1 is a prognostic marker for recurrence: 34 (87.2%) of 39 recurrent cases were positive for MK-1 expression. However, only recurrence was an independent prognostic factor in patients with schistosomiasis- associated squamous cell carcinoma of the bladder.

Distinct serum immunoglobulins pattern in Egyptian patients with chronic HCV infection analyzed by nephelometry.

Hepatitis C has emerged as a major worldwide public health problem. The host immune response to HCV infection is composed of both a non-specific immune response, including interferon (IFN) production and natural killer (NK) cell activity, and a virus-specific immune response, including humoral and cellular components. Susceptibility to infection has been related to immunological disturbances. Several studies have provided experimental evidence of disorders of both cellular and humoral immunity. The present study was carried out to evaluate the serum immunoglobulins level (IgG, IgM, IgA) and IgG-subclasses (IgG1-4) in chronic hepatitis C patients in comparison with healthy control patients. This study included 50 patients with biochemical, serologic, virologic, and histologic evidence of chronic hepatitis C. Total IgG, IgA, and IgM were assayed by nephelometry. IgG subclasses were assayed using human IgG subclasses enzyme immunoassay. The results showed a significant increase of total serum IgG and IgM levels found in patients with chronic HCV compared with the healthy control patients (P < 0.001 for each). There was a statistically significant difference in the IgG subclasses (IgG1 to IgG4) between the patients and controls (P < 0.001 for each). On the other hand, no significant difference was found between patients and healthy controls in IgA level (P = 0.4). The normal total serum immunoglobulins pattern is apparently shifted in chronic hepatitis C infection in the Egyptian patients. This pattern may include an ethnic or biologic background and could be used in the differentiation of the patients with minimal liver disease.

Prognostic value of p53 and MDM2 expression in bilharziasis-associated squamous cell carcinoma of the urinary bladder.

The aim of this study was to elucidate the associations between immunostaining for MDM2 and p53, their respective expression in squamous cell carcinoma of the urinary bladder, and the value of these variables for predicting treatment outcome after cystectomy. Inactivation of TP53 might play a role in the development and progression of bladder cancer. Complex formation with the MDM2 product is one mechanism that inactivates the p53 protein. Therefore, the MDM2 and the p53 protein were investigated to study potential interactions in bladder cancer. Fifty archival bladder tissue specimens were immunohistochemically stained using monoclonal antibodies against p53 and MDM2. Staining for p53 was observed in 48% of the specimens and staining for MDM2 in 20%. Univariate analysis demonstrated a significant correlation between p53 accumulation and survival (p = 0.0101), while the correlation between MDM2 and survival was not significant (p = 0.7183). The combined expression of MDM2 and p53 doest not add to the prognostic information provided by p53 alone.