The influence of Castanea sativa Mill. flower extract on hormonally and chemically induced prostate cancer in a rat model

Prostate cancer (PCa) is one of the most common cancers in men, with a huge impact on their health. The use of Castanea sativa Mill. flowers (CFs) in beverages has been reported, through ancestral claims, as having health benefits. In vitro research has evidenced the properties of CFs, such as antitumor and antioxidant activities. This study aimed to evaluate the effects of CF extract in an animal model of PCa. Forty male Wistar Unilever rats were randomly assigned to four groups: control, induced, control + CF, and induced + CF groups. Animals from the induced groups were exposed to a multistep protocol for PCa induction. The CF extract, rich in trigalloyl-HHDP-glucoside and obtained via decoction, was administered to the CF groups in drinking water (3 mg per animal per day) for 49 weeks. Animals were sacrificed at 61 weeks of age. Regarding the effects of CFs on dorsolateral prostate tumorigenesis, no significant differences were observed between the induced and induced + CF groups. However, animals exposed to the CF extract showed fewer inflammation areas on the dorsolateral prostate lobe than those not exposed to CF. Moreover, the CF extract alleviated the hepatic oxidative stress associated with the multistep protocol, resulting in lower levels of lipid peroxidation. These results suggest that CF extract has antioxidant and anti-inflammatory properties. This journal is.This work was supported by European Investment Funds by FEDER/COMPETE/POCI - Operational Competitiveness and Internationalization and National Funds by FCT - Portuguese Foundation for Science and Technology, under the projects UIDB/04033/2020 (CITAB), UIDB/00690/2020 (CIMO), UIDB/50006/2020 (LAQV), UIDB/CVT/00772/2020 (CECAV), and UIDP/00616/2020 (CQ-VR), the project RUNawayPCa (POCI-01-0145- FEDER-016728 and PTDC/DTP-DES/6077/2014), and PhD fellowship SFRH/BD/136747/2018. L. Barros also acknowledges national funding by FCT, P.I., through the institutional scientific employment program-contract for her contract. The Interreg Program received financial support from the Project IBERPHENOL, Project Number 0377_IBERPHENOL_6_E, cofinanced by the European Regional Development Fund (ERDF) through POCTEP 2014-2020.info:eu-repo/semantics/publishedVersio

Uloga prirodnih spojeva kod raka mliječnih žlijezda u štakora; blagotvorni učinci vodenog ekstrakta Santolina chamaecyparissus L.

Breast cancer is the most diagnosed cancer among women, and a leading cause of death worldwide. Santolina chamaecyparissus L. is a plant with multiple health benefits, including anticancer and anti-diabetic properties. This study aimed to assess the chemopreventive effects of S. chamaecyparissus aqueous extract (SCE) in an animal model of mammary cancer. A total of 28 four-week-old female Wistar rats were divided into four groups: control, MNU-induced (IND), SCE-supplemented (SCE), and SCE+IND. SCE was added to drinking water (12.72 mg/kg body weight) ad libitum. MNU was administered via the intraperitoneal route at 50 days of age. Weekly monitoring of body weight, food/drink intake, humane endpoints, and number of mammary tumours were recorded. Twenty weeks after MNU administration, animals were sacrificed by anaesthetic overdose and a necropsy was performed. Blood samples were used to determine blood count and serum biochemistry analysis, while kidney and liver samples were analysed for oxidative stress. Tumour samples were collected for gene expression and histology studies. SCE chemical composition was analysed by LC-MS and contained 19 phenolic compounds, with the most abundant being myricetin-O-glucuronide and 1,3-O-dicaffeoylquinic acid. Two animals in the IND group were sacrificed due to exceeding the humane endpoint limits. SCE supplementation delayed mammary tumour development, reducing its volume and weight. SCE had a positive impact on haematological parameters, particularly the neutrophil-lymphocyte ratio (P=0.026). No significant differences were observed in serum biochemistry, except for creatinine kinase MB, or in oxidative stress markers. Gene expression analysis showed significantly reduced VEGF expression levels (P=0.0158) in tumours from SCE+IND. These findings suggest that SCE is deserving of further study to identify the individual compounds and to understand its influence on animal models during cancer development.Rak dojke najčešće je dijagnosticiran rak u žena i vodeći uzrok smrti na svijetu. Santolina chamaecyparissus L. je biljka s višestrukim blagotvornim učincima za zdravlje, uključujući antitumorska i antidijabetička svojstva. Cilj je ove studije bio procijeniti kemopreventivne učinke vodenog ekstrakta S. chamaecyparissus (SCE) na životinjama obeljelim od raka mliječnih žlijezda. Dvadeset i osam četiri ženki starih tjedna wistar štakora podijeljeno je u četiri skupine: kontrolnu, MNU-inducirano (IND), s dodatkom SCE (SCE) i SCE+IND. Skupini SCE je dodan vodi za piće (12,72 mg/kg tjelesne mase) ad libitum; MNU je primijenjen intraperitonealnim putem u 50. danu života. Tjedno je bilježeno praćenje tjelesne mase, unosa hrane/tekućine, humano usmrćivanje i broj tumora mliječnih žlijezda. Dvadeset tjedana nakon primjene MNU, životinje su žrtvovane predoziranjem anestetikom i obavljena je razudba. Uzorci krvi su rabljeni za određivanje krvne slike i analizu biokemije seruma, dok su uzeti uzorci bubrega i pluća rabljeni za analize oksidativnog stresa. Uzorci tumora su prikupljeni za studije ekspresije gena i histološke studije. Analiziran je kemijski sastav skupine SCE pomoću LC-MS i otkriveno je da sadrži 19 fenolnih spojeva od kojih su najobilniji bili miricetin-O-glukuronid i 1,3-O-dikafeoilkina kiselina. Dvije životinje iz IND skupini žrtvovane su zbog prekoračenja ograničenja za humano usmrćivanje. Skupini SCE dodatak je odgodio razvoj tumora mliječnih žlijezda, smanjujući njegov volumen i masu. Skupina SCE je imala pozitivni učinak na hematološke parametre, posebice na omjer neutrofila i limfocita (P=0,026). Nikakve značajne razlike nisu otkrivene u biokemiji seruma, osim kreatinin kinaze MB, niti u markerima oksidativnog stresa. Analiza ekspresije gena pokazala je značajno smanjene razina ekspresije VEGF (P=0,0158) u tumora iz skupine SCE+IND. Ovi nalazi ukazuju da bi skupinu SCE trebalo dodatno ispitati da bi se identificirali pojedinačni spojevi i razumio njegov utjecaj na životinjama oboljelih od raka mliječnih žlijezda

Determinant Factors of Dividend Payments in Brazil

This study identifies factors that shaped cash disbursement distribution policies employed by Brazilian public companies listed on the Brazilian Securities, Commodities and Futures Exchange (BM&FBOVESPA) from 1995 to 2011. Relationships between Dividends/Total Assets and potential determinants discussed in the literature, including firm size, corporate governance, profitability, leverage, market to book, liquidity, investment, risk, profit growth, information asymmetry and agency conflict, are examined. The following econometric methods are employed: (1) Tobit, given the nature of the dividend data, and (2) the Generalized Method of Moments (GMM) to control for endogenous regressors. Significant positive variables found include size, return on assets (ROA), market to book, liquidity and profit growth. It can thus be inferred that larger firm size, profitability, market value, liquidity and profit growth correlate with greater firm pro pensity to distribute money to shareholders, thus supporting the theory of corporate finance. Significant negative variables found include leverage, liquidity squared, capex, beta and tag along 100%. It is thus inferred that more significantly leveraged companies that invest more heavily in fixed assets and that exhibit high liquidity, higher risk and less conflict between controlling and minority shareholders will be less likely to pay dividends to shareholders.</p

Profile of Central and Effector Memory T Cells in the Progression of Chronic Human Chagas Disease

Chagas disease is a parasitic infection caused by protozoan Trypanosoma cruzi that affects approximately 11 million people in Latin America. The involvement of the host's immune response on the development of severe forms of Chagas disease has not been fully elucidated. Studies on the immune response against T. cruzi infection show that the immunoregulatory mechanisms are necessary to prevent the deleterious effect of excessive immune response stimulation and consequently the fatal outcome of the disease. A recall response against parasite antigens observed in in vitro peripheral blood cell culture clearly demonstrates that memory response is generated during infection. Memory T cells are heterogeneous and differ in both the ability to migrate and exert their effector function. This heterogeneity is reflected in the definition of central (TCM) and effector memory (TEM) T cells. Our results suggest that a balance between regulatory and effectors T cells may be important for the progression and development of the disease. Furthermore, the high percentage of central memory CD4+ T cells in indeterminate patients after stimulation suggests that these cells may modulate host's inflammatory response by controlling cell migration to tissues and their effector role during chronic phase of the disease

Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants

BACKGROUND: One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age-standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are affecting the number of adults with diabetes. METHODS: We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence—defined as fasting plasma glucose of 7·0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs—in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue. FINDINGS: We used data from 751 studies including 4 372 000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4·3% (95% credible interval 2·4–7·0) in 1980 to 9·0% (7·2–11·1) in 2014 in men, and from 5·0% (2·9–7·9) to 7·9% (6·4–9·7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28·5% due to the rise in prevalence, 39·7% due to population growth and ageing, and 31·8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target. INTERPRETATION: Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults affected, has increased faster in low-income and middle-income countries than in high-income countries. FUNDING: Wellcome Trust