This research paper addresses the hypothesis that stress, induced by ACTH administration and cortisol release increases somatic cell count (SCC) in mammary secretion, and improves the effectiveness of dry off in goats. We report indicators of milk synthesis and mammary gland involution during dry off. Thirty Saanen goats were subjected to abrupt dry off and treatments: (1) ACTH administration (ACTH) or (2) placebo (Control) on days 1, 3, 6, 9, 12, 15, 30, and 60 of dry off. The expression of target genes in mammary tissue that are related to milk synthesis and cell survival such as insulin-like growth factor 1 receptor (IGF1R), phosphatidylinositol-3-kinase (PIK3CA), protein kinase B (AKT1) and mechanistic target of rapamycin (MTOR), casein (CSN2), lactalbumin (LALBA) and lactoferrin (LF) were evaluated, and plasma cortisol concentration, SCC, leucocyte count, and microbiological analyses in milk and mammary secretions were assessed. ACTH significantly downregulated the expression of IGF1R and upregulated the expression of PIK3CA in mammary tissue, increased lactoferrin concentration and SCC, and changed immune cell levels in mammary secretions compared to Control. Furthermore, ACTH administration increased the percentage of dry goats compared to the Control (73 vs. 46%, respectively). We conclude that the effect of stress via ACTH administration and cortisol release accelerated mammary involution during the early dry-off period.

Thromboembolic disorders are the second leading cause of death in breast cancer. Antiplatelet therapy combined with cancer therapy is a potential treatment strategy against cancer-associated thromboembolic disorders; however, the efficacy of such dual treatment has not been established. This study reports novel findings on the response of hormone-dependent breast cancer cell lines (MCF7/T47D) following 24 h treatment with Anastrozole, combined with Aspirin and Clopidogrel cocktail; and Atopaxar. Neutral red and lactate dehydrogenase assays were conducted to assess viability and cytotoxicity respectively. Flow cytometric Annexin-V/PI assay was used to assess the mode of cell death. Morphological alterations were studied using scanning electron microscopy. Statistical analysis was conducted using Statistica V13. Definitive outcomes were established with flow cytometric detection of phosphatidylserine exposure and propidium iodide staining, complemented with ultrastructural analysis. Results showed that a few cells were undergoing death mainly through secondary necrosis. Morphological features suggesting induced cell motility (pseudopodia/ruffled membranes) were observed in both cell lines; notably, T47D cells presented pronounced features than MCF7 cells. Overall, these findings suggest that such combined treatment may differentially promote cell survival, inducing a more aggressive breast cancer phenotype.

Activated pERK1/2 and pAKT are key players in supporting cell survival and proliferation pathways. Translocation of pERK1/2 into the nucleus, where it interacts with transcription factors and DNA itself, is instrumental in exerting an anti-apoptotic effect. In this study, pAKT levels, pERK1/2 nuclear localization and DNA fragmentation index (DFI) in cumulus cells of single cumulus–oocyte complexes of patients undergoing in vitro fertilization programmes were evaluated and correlated with the clinical outcome of the related embryos. For a positive clinical outcome of blastocyst development, pERK1/2 nuclear localization and DFI value had a significant inverse relationship, whereas the former and the intracellular accumulation of pAKT had a significant direct relationship. This relationship was not observed for the negative clinical outcome of the arrested embryos. Moreover, intracellular accumulation of pAKT and DFI value had a significant inverse relationship in all samples examined. The obtained data suggest that the intranuclear relocation of pERK1/2, along with an enhanced intracellular accumulation of pAKT, may exert a survival effect and increase cell viability, therefore providing a novel marker tool to choose the best oocyte to be fertilized and submitted to an intracytoplasmic sperm injection cycle.

Ragweed Parthenium (Parthenium hysterophorus L. # PTNHY) was found to exhibit autotoxicity. The active principle(s) were isolated from two parts of the plant using polar system. Principle(s) from the inflorescence were more effective than from the leaves. Leachates derived from the plant decreased percent cell survival and chlorophyll content. Leachates from leaves were more toxic to ragweed parthenium when applied to the foliage than when applied through the roots. The polar allelochemicals were highly effective in preventing rooting and sprouting of stem cutting and in reducing the regeneration potential of mature ragweed parthenium plants.

The aim of the present paper is to give a brief overview on the role of dietary fat in carcinogenesis and as possible anticancer agents. Dietary fat is an essential nutrient and important source for the essential fatty acids (FA), linoleic and α-linolenic acids, which contribute to proper growth and development. However, dietary fat has been associated with the development of colorectal, breast, prostate, endometrial and ovarian cancers, with the type and quality of fat playing an underlying role. Tumour growth is the disruption of the homoeostatic balance regulating cell differentiation, proliferation and apoptosis and is associated with altered lipid metabolism. Animal cancer models and human cancer biopsy tissue demonstrate that a characteristic lipid profile is associated with the growth and development of neoplastic lesions. This entails alterations in membrane cholesterol, phospholipid and PUFA metabolism. Particularly, alterations in cell membrane FA metabolism involving the n-6 and n-3 PUFA, are associated with changes in membrane structure, function, cellular oxidative status, activity of enzymes and signalling pathways. These events are a driving force in sustaining the altered growth of cancerous lesions and provide unique targets for intervention/cancer modulation. Challenges in utilising FA in cancer modulation exist regarding intake and effect on cell structure and biochemical interactions within the cell in the prevention of cancer development. Therefore, utilising dietary PUFA in a specific n-6:n-3 ratio may be an important chemopreventive tool in altering the growth characteristics of cancer cells.

Myostatin (MSTN), a member of the TGF-β superfamily, is a negative regulator of skeletal muscle mass. We have previously shown that the cell survival/apoptosis pathway is a downstream target of MSTN loss-of-function in mice through the regulation of the expression or abundance of many survival and apoptotic factors. In this study, we used western-blot and quantitative PCR (qPCR) analyses to validate these novel downstream targets of MSTN in double-muscled (DM) cattle v. their controls including 260-day-old foetuses and adult cows from the INRA95 strain. MSTN loss-of-function in DM foetuses and DM cows resulted in a glycolytic shift of the muscles (e.g. upregulation of H-MyBP, PGM1 and SNTA1 and downregulation of H-FABP), activation of cell survival pathway through regulation of some components of the PI3K/Akt pathway (e.g. upregulation of DJ-1 and Gsk-3βser9/Gsk-3βtotal ratio and downregulation of PTEN) and upregulation of cell survival factors translationally controlled tumour protein (14-3-3E, Pink1). We also found a lower abundance of pro-apoptotic transcripts and/or proteins (Caspase-3, caspase-8, caspase-9, BID, ID2 and Daxx) and a higher expression of anti-apoptotic transcripts (Traf2 and Bcl2l2) in DM muscles. All together, these results are in favour of activation of the cell survival pathway and loss of apoptosis pathway within the muscles of DM animals. Alteration of both pathways may increase myonuclear or satellite cell survival, which is crucial for protein synthesis. This could contribute to muscle hypertrophy in DM foetuses and DM cows.

Equivalent Uniform Dose (EUD) has been proposed as a means of comparing treatment plans which include large PTV dose heterogeneity. Moreover, it has been suggested that EUD is insensitive to the underlying cell survival model parameters used in its calculation, and that arbitrary values might be used. This dependence of EUD on radiobiological parameters has been studied using different cell survival models (exponential and linear quadratic) and a range of artificially generated and clinical (lung and prostate) treatment plans. EUD was found to be strongly dependent on the variable SF2, but not on α/β, or number of fractions. When clinical treatment plans were ranked in order of EUD, a dependence of rank order on SF2 was observed, suggesting that arbitrary SF2 values are not appropriate for treatment plan evaluation. These results suggest that tumour specific SF2 values should be used for EUD calculation, and this is discussed.

We analysed whether markers of cell differentiation and infectivity differed when compared to the parental sensitive strain [NR(Gs)] in an in vitro selected Leishmania strain [NR(Gr)] resistant to Glibenclamide®, an ATP-binding-cassette (ABC)-transporter blocker. The data show that the cell body area was larger in NR(Gr) compared to NR(Gs) and that functional characters associated with an infective metacyclic phenotype, such as resistance to the lytic effect of the alternative complement pathway and expression of the Meta-1 protein, were reduced. The infectivity of NR(Gr) to J774.1 macrophages was also significantly reduced. These results suggest that resistance in Leishmania against Glibenclamide®, a general blocker of P-glycoproteins, could produce functional modifications that may be relevant for Leishmania differentiation, infectivity and survival.