Therapeutic trial of fluvastatin in a cell line xenograft model of canine mammary gland cancer

The Hippo signalling pathway is involved in breast cancer and canine mammary tumour (CMT). This study sought to evaluate the efficacy of fluvastatin on the Hippo pathway and its main effectors, YAP and TAZ, in vivo in a murine CMT cell line xenograft model. On treatment day 1, mice were divided into four groups: vehicle, fluvastatin, doxorubicin or a combination therapy. Tumour volumes were monitored with callipers and tissues harvested on day 28th of treatment. Histopathological examination of tumour tissues and major organs was performed as well as tumour evaluation of necrosis, apoptosis, cellular proliferation, expression of YAP, TAZ and the mRNA levels of four of their target genes (CTGF, CYR61, ANKRD1 and RHAMM2). Results showed a statistically significant variation in tumour volumes only for the combination therapy and final tumour weight only for the doxorubicin group compared to control. There was no significant difference in tumour necrosis, expression of CC3, ki-67, YAP and TAZ measured by immunohistochemistry and in the mRNA levels of the target genes. Unexpectedly, lung metastases were found in the control group (9) and not in the fluvastatin treated group (7). In addition, mass spectrometry-based quantification of fluvastatin reveals concentrations comparable to levels reported to exert therapeutic effects. This study shows that fluvastatin tumours concentration reached therapeutic levels without having an effect on the hippo pathway or various tumour parameters. Interestingly, only the control group had lung metastases. This study is the first to explore the repurposing of statins for cancer treatment in veterinary medicine.     

Interaction between chromaffin and sustentacular cells in adrenal medulla of viscacha (Lagostomus maximus maximus)

New evidence provides valuable information about the participation of sustentacular cells in chromaffin cell catecholamine secretion. In this process, calcium ions play an important role. It has been shown that there is an intense ionic traffic between both types of cells. Moreover, sustentacular cells take an active part in calcium metabolism, regulating levels of the ion and indirectly, the synthesis and release of catecholamines. This background information encouraged us to study the sustentacular population of Lagostomus adrenal medulla and its morphologic relationship with the chromaffin population. The animals were captured, transported to the animal facilities, anaesthetized and killed. The adrenal gland was processed by immunohistochemistry using antiserum against S-100 (subunit alpha and beta), a specific marker. Through the morphological and immunohistochemical study, it was found that there are sustentacular cells in deferent regions of adrenal medulla, mainly in the basal zone of chromaffin cells, which constitute the glomerular structure around blood capillaries. Cytoplasmic extentions of sustentacular cells penetrate into chromaffin cells and make contact with the basal membrane of the capillary endothelium. The relationship among chromaffin cells, capillaries and sustentacular cells suggests that they may intervene actively in the adrenal medulla metabolism.     

Induction of proinflammatory cytokines and caspase-1 by leptin in monocyte/macrophages from holstein cows

The proliferation of peripheral blood mononuclear cells (PBMC) containing both monocyte/macrophages and T lymphocytes increased after treatment with T-cell mitogen (concanavalin A: Con A). PBMC treated with either leptin alone or combination of leptin and ConA showed enhanced proliferative activity by 10-40%, compared with those treated with ConA alone. In contrast, isolated T lymphocytes treated with leptin and ConA showed lowered proliferative activity than the ConA-treated alone, indicating that leptin induced production of some cytokines from monocyte/macrophages, that subsequently resulted in enhancement of T lymphocytes proliferation in PBMC. Among the cytokines examined, monocyte/monocytes constitutively expressed interleukin (IL)-1beta, IL-12p35, IL-18 mRNA, and faintly expressed tumor necrosis factor (TNF)-alpha and IL-12p40 mRNA. Leptin treatment augmented the monocyte/macrophages mRNA expression of only TNF-alpha and IL-12p40 to comparable levels of cells treated with lipopolysaccharide (LPS). However, leptin treatment increased monocyte/macrophages production of IL-1beta as well as TNF-alpha, and induced the mRNA expression of caspase-1, which is shown to mediate the conversion of latent pro-IL-1beta and pro-IL-18 to active forms. These results suggest that leptin directly acts on monocyte/macrophages to produce factors that induce T lymphocytes proliferation such as IL-12p35/p40 complex through IL-12p40 induction and IL-1beta/IL-18 production through caspase-1 induction.     

A survey of rift valley fever and associated risk factors among the one-humped camel (<Emphasis Type="Italic">Camelus dromedaries</Emphasis>) in Sudan

Background

Rift valley fever (RVF) is a mosquito-borne viral disease of domestic livestock and wild ruminants. In camels RVF may cause abortion among pregnant camels, but is most often asymptomatic among other camels. In this study, a seroepidemiological survey was conducted to determine the prevalence of RVFV antibodies and to identify the potential risk factors associated with RVFV seropositivity among the Sudanese one-humped camel (Camelus dromedaries) in Khartoum State, Sudan. A cross sectional study was conducted in Khartoum State, Sudan, in a total of 240 camels selected randomly from four localities. Sera sampled were tested for the presence of RVFV-specific immunoglobulin G (IgG) antibodies using a competitive enzyme-linked immunosorbent assay (c-ELISA).

Results

RVFV seropositivity was recorded in 23 out of 240 animals, prevalence rate of 9.6 % among camels in Khartoum State. Age (OR?=?8.29, p-value?=?0.04) and heavy rainfall (OR?=?5.36, p value?=?0.01) were recorded as potential risk factors for contracting RVF.

Conclusions

Older age and heavy rainfall were considered as potential risk factors for seropositivity to RVF. Surveillance for RVF among camels and distribution of mosquito vectors should continue to better understand the clinical signs associated with RVFV infection in camels and provide public health authorities an opportunity to anticipate and prepare for a possible RVF outbreak in Khartoum State, Sudan.

     

Prevalence of amyloid deposition in mature healthy chickens in the flock that previously had outbreaks of vaccine-associated amyloidosis

Avian amyloid A (AA) amyloidosis is commonly observed in adult birds with chronic inflammation, such as that caused by bacterial infection. We previously described vaccine-associated AA amyloidosis in juvenile chickens. In this study, the prevalence of amyloid deposition was measured in mature healthy chickens that survived a previous outbreak of avian AA amyloidosis while they were juveniles. Herein, we analyzed the amyloid deposition in mature chickens and compared the prevalence of amyloid deposition with juvenile chickens obtained in our previous study (Murakami et al., 2013). We found that: 1) amyloid deposition in the liver was absent in mature chickens, while juvenile chickens had a rate of 24%; 2) amyloid deposition in the spleen was observed in 36% of juvenile chickens and in 40% of mature chickens; 3) amyloid deposition in the pectoral muscle of mature chickens (43.75%) was approximately half that of juvenile chickens (88%). These results suggest that additional amyloid deposition in chickens previously exposed to AA amyloidosis may not worsen with age. Further, amyloid deposition in chickens may tend to regress when causative factors, such as vaccinations and/or chronic inflammation, are absent.     

Risk assessment of pesticide residues in South African raw wheat

The presence of pesticide residues in wheat produced and imported in South Africa was determined and their health risks assessed. Pesticides were detected in all local (median = 1, range: 1–3, n = 71) and imported (median = 1, range: 1–6, n = 13) samples. Multiple pesticides (>1 pesticide) were detected in about 30% local samples and 39% imported samples. Eight different pesticides were detected in total. The most frequently detected pesticides were mercaptothion (99%), permethrin (19%) and chlorpyrifos (17%). Nine (11%) samples exceeded the EU wheat MRL for permethrin (0.05 mg/kg) which included 7 (10%) local samples and 2 (15%) imported samples. The highest fenitrothion level (0.65 mg/kg) corresponds to an intake that was below but near the estimated short-term safety threshold. The results call for an investigation into the levels of pesticide residues in cereal-based food and for tighter regulation and regular monitoring by government and industry.     

Effect of growth stage on the content and composition of the essential oil and phenolic fraction of sweet marjoram (Origanum majorana L.)

The variation in the content and composition of Origanum majorana L. essential oil has been studied. Plant material has been harvested at four phenological stages (early vegetative, late vegetative, budding and full-flowering). Essential oil yield varied from 0.04 to 0.09% reached during the full-flowering stage. Analysis of the essential oils by GC and GC/MS revealed the presence of 38 components represented mainly by oxygenated monoterpenes (64.01–71.4%), monoterpene hydrocarbons (21.73–29.92%) and sesquiterpene hydrocarbons (1.47–4.05%). The main components were terpinen-4-ol (29.13–32.57%), cis-sabinene hydrate (19.9–29.27%), trans-sabinene hydrate (3.5–11.61%), γ-terpinene (2.11–8.20%), bornyl acetate (1.52–2.94%) and linalool (1.05–1.39%). On the other hand, phenolic contents varied from 2.706 to 6.834 mg/g of dry weight obtained during the later vegetative stage. RP-HPLC analysis of the methanolic extract of O. majorana L. dried aerial parts showed the predominance of phenolic acids during the early vegetative stage whereas flavonoids predominate during the other stages of growth. The main phenolic acids identified were trans-2-hydroxycinnamic, rosmarinic, vanillic, chlorogenic, gallic and cinnamic whereas the main flavonoids were amentoflavone, apigenin, quercetin, luteolin, coumarin and rutin. Results obtained showed that later vegetative stage is characterized by the highest contents of bioactive compounds and therefore it could be considered as the best stage for harvesting marjoram plants.     

Araguspongine C Induces Autophagic Death in Breast Cancer Cells through Suppression of c-Met and HER2 Receptor Tyrosine Kinase Signaling

Receptor tyrosine kinases are key regulators of cellular growth and proliferation. Dysregulations of receptor tyrosine kinases in cancer cells may promote tumorigenesis by multiple mechanisms including enhanced cell survival and inhibition of cell death. Araguspongines represent a group of macrocyclic oxaquinolizidine alkaloids isolated from the marine sponge Xestospongia species. This study evaluated the anticancer activity of the known oxaquinolizidine alkaloids araguspongines A, C, K and L, and xestospongin B against breast cancer cells. Araguspongine C inhibited the proliferation of multiple breast cancer cell lines in vitro in a dose-dependent manner. Interestingly, araguspongine C-induced autophagic cell death in HER2-overexpressing BT-474 breast cancer cells was characterized by vacuole formation and upregulation of autophagy markers including LC3A/B, Atg3, Atg7, and Atg16L. Araguspongine C-induced autophagy was associated with suppression of c-Met and HER2 receptor tyrosine kinase activation. Further in-silico docking studies and cell-free Z-LYTE assays indicated the potential of direct interaction between araguspongine C and the receptor tyrosine kinases c-Met and HER2 at their kinase domains. Remarkably, araguspongine C treatment resulted in the suppression of PI3K/Akt/mTOR signaling cascade in breast cancer cells undergoing autophagy. Induction of autophagic death in BT-474 cells was also associated with decreased levels of inositol 1,4,5-trisphosphate receptor upon treatment with effective concentration of araguspongine C. In conclusion, results of this study are the first to reveal the potential of araguspongine C as an inhibitor to receptor tyrosine kinases resulting in the induction of autophagic cell death in breast cancer cells.     

Phosphorus Adsorption Isotherm: A Key Aspect for Effective Use and Environmentally Friendly Management of Phosphorus Fertilizers in Calcareous Soils

Crop response to the phosphorus (P) application is often erratic in most soil types in the world. In Algeria, there is no information on the P behavior in calcareous soils. The purposes of this work were to investigate the degree of P fixing capacity and to predict P fertilizer requirements of crops according to calcareous levels in the soil. Soil samples (at 0–30 cm depth) were collected and spiked with 0, 25 and 50% of lime (CaCO₃). Phosphate sorption curves were well fitted to the Freundlich equation. Results indicated that the calcareous level was predominantly controlled the P sorption indices [sorption capacity (a), and P sorption energy (n)] to affect the estimation of external d P requirement (EPR_0.2) and P fertilizer rates. The understanding of P sorption and desorption by soils and extrapolating the developed relationship between soil calcareous contents and P fertilizer rates would be quite promising and accurate approach for the economic and effective use of P fertilizers in calcareous soils of Algeria.     

Nutrient uptake and use efficiencies in Medicago ciliaris under salinity

Salt-induced responses of Medicago ciliaris was studied under controlled conditions. Twenty-two-day old seedlings were cultivated for one month in a nutrient medium added or not with 75 mM sodium chloride (NaCl). Our results showed that this species is relatively salt-tolerant since the whole biomass production of salt-treated plants was affected a little (?30%) as compared to the control. The slight salt effect was mainly nutritional and concerned both macro potassium, calcium and magnesium (K, Ca, and Mg) and micro-nutrients iron (Fe). K and Fe uptake efficiencies were more affected than those of Ca and Mg. Nevertheless, M. ciliaris was able to counterbalance this impact by increasing both K and Fe use efficiencies. The enhancement of K use efficiency could be due in part to the plant aptitude to accumulate sodium (Na⁺) ions within its shoot tissues and to use them for osmotic adjustment. This “includer” behavior allowed M. ciliaris to maintain an adequate water status under saline conditions.