Valsartan as a prophylactic treatment against breast cancer development and niche activation: What molecular sequels follow chronic AT-1R blockade?

AIMS: Transactivation of insulin-growth-factor-receptor (IGF-1R) by angiotensin-II-type-1-receptor (AT-1R) was only demonstrated in vascular-smooth-muscle cells and has never been tested in breast-cancer (BC). This investigation addressed the impact of chronic AT-1R blockade by valsartan (Val) on possible concurrent AT-1R/IGF-1R signaling inhibition, regressing BC-tumor-microenvironment (TME) cellular components activation, and hindering BC development. MAIN METHODS: The effect of different Val doses (10, 20, 40 & 80 mg/kg/day for 490 days) was tested on dimethylbenz(a)anthracene (DMBA)-induced progesterone-promoted-BC in rats. The influence on intratumoral/circulating angiotensin-II (ANG-II) levels and AT-1R/Mas-R immunofluorescent-expression were assessed. The potential AT-1R/IGF-1R crosstalk within TME-BC-stem-cells (BCSCs) and cancer-associated-fibroblasts (CAFs) was evaluated by fluorescently marking these cells and locating the immunofluorescently-stained AT-1R/IGF-1R in them using confocal-laser-microscopy and further quantified by flow cytometry. In addition, the molecular alterations following blocking AT-1R were inspected including determining Src; crucial for IGF-1R transactivation by AT-1R, Notch-1; IGF-IR transcriptional-regulator, and PI3K/Akt &IL-6/STAT expression. Further, the suppression of CSCs' capabilities to maintain pluripotency, stemness features, epithelial-to-mesenchymal-transition (EMT), and angiogenesis was evaluated by assessing NANOG gene, aldehyde-dehydrogenase (ALDH), N-cadherin and vascular-endothelial-growth-factor (VEGF), respectively. Furthermore, the proliferative marker; Ki-67, was detected by immunostaining, and tumors were histologically graded using Elston-Ellis-modified-Scarff-Bloom-Richardson method. KEY FINDINGS: Prophylactic Val significantly reduced tumor size, prolonged latency, reduced tumor histopathologic grade, decreased circulating/intratumoral-ANG-II levels, increased Mas-R, and decreased AT1R expression. AT-1R/IGF-1R were co-expressed with a high correlation coefficient on CAFs/BCSCs. Moreover, Val significantly attenuated IGF-1R transactivation and transcriptional regulation via Src and Notch-1 genes' downregulation and reduced Src/IGF-IR-associated PI3K/Akt and IL-6/STAT3 signaling. Further, Val significantly decreased intratumoral NANOG, ALDH, N-cadherin, VEGF, and Ki-67 levels. SIGNIFICANCE: Chronic Val administration carries a potential for repurposing as adjuvant or conjunct therapy for patients at high risk for BC.

Consequences of dietary cinnamon and ginger oils supplementation on blood biochemical parameters, oxidative status, and tissue histomorphology of growing Japanese quails.

The present study aimed to investigate the impact of various concentrations of ginger and cinnamon oils as antibiotic substitutes on some blood biochemical parameters, antioxidant capacity, and histopathological profile of the liver and gut of growing Japanese. A total of 900 Japanese quails were randomly allotted into 6 treatment groups. Each group had 5 replicates (30 chicks each). The first group received a basal diet and served as the control, while the second received a basal diet plus 0.5 g of colistin antibiotic/kg diet. The third and fourth groups were supplemented with 0.5 mL and 1.0 mL of ginger oil (GO)/kg diet, respectively. While the fifth and sixth groups received basal diet with 0.5 and 1.0 mL of cinnamon oil (CO)/kg diet, respectively. Results showed that adding herbal oils significantly (P < 0.05) decreased the aspartate aminotransferase (AST) and urea levels compared to control and colistin groups. Various levels of GO and CO significantly (P < 0.05) reduced cholesterol levels compared to control birds. Compared to the control and antibiotic groups, Japanese quails supplemented with various levels of herbal oils (GO and CO) had more extraordinarily significant (P < 0.05) values for total antioxidant capacity (TAC), superoxide dismutase (SOD), glutathione peroxidase (GPX), and glutathione reductase (GSR). Regarding histopathologic examination, the jejunum displayed a nearly empty lumen, a few fusions, and mild goblet cell metaplasia. On the other hand, the duodenum looked tall and had a few fusions of villi and remnants of removal in its lumina. It could be concluded that cinnamon and GO improved birds' blood biochemical parameters, electorate oxidative stress, and enhanced intestinal and hepatic histology of the treated quails. Also, the levels of 0.5 mL CO and 0.5 mL GO may be an acceptable substitute for antibiotics (colistin) in the diets of growing Japanese quail.

Influence of tomato processing by-product extract as dietary supplementation on growth performance, carcass characteristics and antioxidant status of growing rabbits under high ambient temperature.

This study evaluated the effects of dietary supplementation of tomato processing by-product extract (TPBE) on growth performance, carcass characteristics and antioxidant status of growing rabbits under high ambient temperature. A total of eighty weaned New Zealand White (NZW) male rabbits (6-weeks-old; initial body weight, 730.28 ± 36.05 g) were randomly assigned to 4 groups. The first group was the control without supplementation; while the other groups were fed diets supplemented with 100, 200 and 250 mg TPBE/kg. The results showed that TPBE contained 211.85 mg/100g as total phenols and total flavones of 303.36 mg/100g. Rabbits fed a 250 mg TPBE-supplemented diet showed the heaviest body weight, the lowest feed intake and the best feed conversion ratio. TPBE diets reduced mortality percentage. Dietary supplementation of 250 mg TPBE had the highest dressing percentage. Plasma total protein, globulin, catalase and glutathione peroxidase of rabbits fed diets supplemented with 200 and 250 mg TPBE were high. Plasma total cholesterol, triglycerides, plasma hydrogen peroxide and malondialdehyde concentrations were decreased with dietary levels of TPBE. Rabbits fed 250 mg TPBE had higher T-AOC than the other groups. TPBE supplemented diets improved net revenue and economic efficiency. Conclusively, TPBE is containing appreciable content of polyphenols and flavonoids and the dietary supplementation of TPBE (250 mg/kg diet) had a positive impact on growth performance, reducing mortality and enhancing the antioxidant status of rabbits reared under high ambient temperature.

Rice gluten meal as a substitute for soybean meal in the diets for growing rabbits.

The impacts of different dietary levels of rice gluten meal (RGM) on growth performance, digestibility, carcass characteristics, and blood traits of growing New Zealand White (NZW) rabbits were studied. One hundred and twenty, 6 weeks old weaned male rabbits (body weight; 682 [g] ± 23) were randomly allotted into four groups. The control diet contained 160 [g/kg] soybean meal (SBM), while the other three diets were obtained by replacing 40, 80, and 120 [g/kg] SBM with RGM (RGM40, RGM80, and RGM120, respectively). The results showed that RGM contained higher levels of dry matter (DM), crude protein (CP), ether extract (EE), ash, and gross energy than SBM. RGM contained a high level of arginine followed by leucine and valine as essential amino acids and high levels of glutamic, aspartic acid, and alanine as non-essential amino acids. The obtained results showed that the final body weight of rabbits fed diets containing 40, 80, and 120 [g/kg] RGM was higher than those fed the control diet. The daily weight gain of rabbits fed RGM diets increased (p < 0.05) by 10.50%, 6.50%, and 10.00%, respectively, compared to the control group. Rabbits fed RGM80 showed the highest (p < 0.05) digestibility of DM, organic matter (OM), EE, neutral detergent fibre (NDF), and acid detergent fibre (ADF) compared to the other tested levels. Rabbits fed RGM120 had the highest (p < 0.05) digestible energy (DE) and digestible crude protein (DCP) values. RGM inclusion levels of 40 and 80 [g/kg] increased (p < 0.05) plasma total protein and albumin compared to the control group. Rabbits fed a diet containing RGM40 had the highest (p < 0.05) globulin level. The highest (p < 0.05) plasma urea concentration level was measured in the rabbit group fed the RGM120 diet. Conclusively, RGM could be a valuable ingredient for growing rabbits, as at all the tested levels improved growth performance, digestibility, and nutritional values.

Intranasal Oxytocin Attenuates Cognitive Impairment, ß-Amyloid Burden and Tau Deposition in Female Rats with Alzheimer's Disease: Interplay of ERK1/2/GSK3ß/Caspase-3.

Oxytocin is a neuropeptide hormone that plays an important role in social bonding and behavior. Recent studies indicate that oxytocin could be involved in the regulation of neurological disorders. However, its role in modulating cognition in Alzheimer's disease (AD) has never been explored. Hence, the present study aims to investigate the potential of chronic intranasal oxytocin in halting memory impairment & AD pathology in aluminum chloride-induced AD in female rats. Morris water maze was used to assess cognitive dysfunction in two-time points throughout the treatment period. In addition, neuroprotective effects of oxytocin were examined by assessing hippocampal acetylcholinesterase activity, ß-amyloid 1-42 protein, and Tau levels. In addition, ERK1/2, GSK3ß, and caspase-3 levels were assessed as chief neurobiochemical mediators in AD. Hippocampi histopathological changes were also evaluated. These findings were compared to the standard drug galantamine alone and combined with oxytocin. Results showed that oxytocin restored cognitive functions and improved animals' behavior in the Morris test. This was accompanied by a significant decline in acetylcholinesterase activity, 1-42 ß-amyloid and Tau proteins levels. Hippocampal ERK1/2 and GSK3ß were also reduced, exceeding galantamine effects, thus attenuating AD pathological hallmarks formation. Determination of caspase-3 revealed low cytoplasmic positivity, indicating the ceasing of neuronal death. Histopathological examination confirmed these findings, showing restored hippocampal cells structure. Combined galantamine and oxytocin treatment showed even better biochemical and histopathological profiles. It can be thus concluded that oxytocin possesses promising neuroprotective potential in AD mediated via restoring cognition and suppressing ß-amyloid, Tau accumulation, and neuronal death.

Effects of ecofriendly synthesized calcium nanoparticles with biocompatible Sargassum latifolium algae extract supplementation on egg quality and scanning electron microscopy images of the eggshell of aged laying hens.

In the present study, 200 Brown commercial egg-type layers (60 wk old) were used to study the effects of different levels of ecofriendly synthesis of calcium (Ca) nanoparticles (0.0, 0.50, 1.0, and 1.5 g/kg diet) with biocompatible Sargassum latifolium algae extract (SL-CaNps) on exterior egg quality traits, electronic microscopic view of eggshells, Ca and phosphorus (P) retention, serum Ca and P concentrations, and the histology of the uterus. Hens fed with dietary SL-CaNps powder had higher egg weight and shell weight % values than those of the control group. All SL-CaNps treatment groups had the greatest values of shell weight per unit surface area and shell thickness. Dietary supplementation of SL-CaNps at graded levels up to 1.5 g/kg diet had higher serum Ca and inorganic P levels than that of the control. Laying hens fed with SL-CaNps-added diets had beneficial effects on shell ultrastructure in terms of well-developed palisade and mammillary layers. The numbers of apical cells along the branched tubular gland were greater in SL-CaNps-treated groups than those of control. Conclusively, supplementing SL-CaNps powder up to 1.5 g/kg to the diet of laying hens improved eggshell thickness, shell weight% and shell weight per unit surface and has no adverse effect on their eggshell quality or electronic microscopic view of their eggshell.