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Breast cancer is the most commonly diagnosed cancer and is one of the leading causes of cancer mortality in women worldwide. Natural product compounds have attracted significant attention for their potent effects against human cancers. Aloin, a natural phytochemical anthraquinone glycoside extracted from Aloe sp., has been previously reported for its antitumor activity. Autophagy is a highly conserved process that mediates the degradation of dysfunctional cellular components, such as senescent proteins and organelles. In the present study, we verified the involvement of autophagy in tolerance to aloin, especially in breast cancer cells with negative estrogen receptors, and as an alternative pathway to promote cell death in cells expressing mutant p53 status, which often limits the efficacy and accounts for resistance to chemotherapy. We studied the effect of aloin on 2 types of breast cancer cell lines, estrogen receptor-positive (T47D) and triple negative (MDA-MB231), and compared to an anthraquinone analog, doxorubicin (Dox) as a reference compound. Aloin inhibited the cell growth of both T47D and MDA-MB231 cancer cells, in a time- and dose-dependent manner with a more pronounced effect in the 72 h exposure regimen, and in the ERα+ breast cell line. The autophagic activity of aloin was emphasized by the formation of autophagosomes and autolysophagosomes, as early and late autophagic compartments, respectively, as well as the accumulation of acidic vesicular organelles in the tumor cells. Also, upregulation in the protein expression of some marker genes of autophagy such as beclin 1 and LC3BII/LC3I, and conversely down-regulation in p-mTOR and p62 was recorded. The results suggest that autophagy can be regarded as one of the mechanistic modes of aloin cytotoxicity in breast cancer cells that evade apoptosis through genetic mutations in p53. [ABSTRACT FROM AUTHOR]

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Directed evolution using error-prone polymerase chain reaction was employed in the current study to enhance the catalytic efficiency of a thermostable Geobacillus stearothermophilus xylanase XT6 parent. High-throughput screening identified two variants with enhanced activity. Sequencing analysis revealed the presence of a single-amino acid substitution (P209L or V161L) in each variant. The maximum activity of mutant V161L and P209L was at 85°C and 70°C, respectively. Both mutants exhibited maximum activity at pH 7. The thermal and alkaline tolerance of mutant V161L only were markedly improved. The two mutants were more resistant to ethanol inhibition than the parent. Substrate specificity of the two mutants was shifted from beechwood xylan to birchwood xylan. The potential of the two mutants to hydrolyze rice straw and sugarcane bagasse increased. Both turnover number (k cat) and catalytic efficiency (k cat/ k M) increased 12.2- and 5.7-folds for variant P209L and 13- and 6.5-folds for variant V161L, respectively, towards birchwood xylan. Based on the previously published crystal structure of extracellular G. stearothermophilus xylanase XT6, V161L and P209L mutation locate on βα-loops. Conformational changes of the respective loops could potentiate the loop swinging, product release and consequently result in enhancement of the catalytic performance. [ABSTRACT FROM AUTHOR]

The hepatoprotective potential of sulfated polysaccharide (SPS) from Ulva fasciata seaweed against galactosamine (GalN)-induced hepatotoxicity was investigated. Subcutaneous injection of 300 mg/kg GalN into rats caused acute liver injury as manifested by the downregulation of sirtuin 1 (SIRT1) gene expression and induction of hepatic proinflammatory cytokines production, and fibrosis as demonstrated by the significant upregulation of hepatic transforming growth factor beta 1 (TGF-β1) and collagen type I (Col1a1) genes expression. Conversely, pretreatment of rats with SPS attenuated GalN-induced hepatotoxicity via inducing liver SIRT1 gene expression and suppressing proinflammatory cytokines synthesis, which ultimately reduced liver fibrogenesis. Histological findings of liver tissues verified the biochemical data. The study clarified some of the molecular mechanisms by which SPS isolated from U. fasciata protects the liver against acute GalN-induced injury. Practical applications The results suggest the potential use of this edible SPS isolated from Ulva fasciata as a food additive to prevent and/or attenuate development of hepatitis. [ABSTRACT FROM AUTHOR]

This study was carried out to evaluate the effect of different levels of water thyme extract (WTE) on New Zeland White (NZW) growing male rabbits performance. Thirty sex rabbits with average body weight of 830 ± 50 g were assigned to 4 groups (9 rabbits per each group). Rabbits in the first group drank tap water (control group), while rabbits of the 2nd, 3rd and 4th groups drank WTE on concentrations of 0.25, 0.50 and 0.75% (W/V), respectively. Gas chromatography-mass spectrometry (GC- MS) was used for determination the WTE constituents. Results showed that, 100 peaks were obtained when WTE was subjected to GC-MS. The peaks area more than 0.5% were 10 peaks which corresponding to 10 compounds. The best (P<0.05) average daily body weight gain and feed conversion for total period (8 weeks) were obtained when rabbits drank 0.25% WTE as compared to control and other treated levels. The daily feed intake of all levels of WTE significantly (P<0.05) reduced. The mortality rate (%), average water intake, digestibility of all nutrients, nutritive values and carcass traits did not significantly differ between all tested levels of WTE and control. Caecum parameters (total volatile fatty acids, ammonia-N and pH values) were significantly (P<0.05) decreased when rabbits drank all levels of WTE in comparison with control rabbits. Results of blood analysis showed that, all levels of WTE did not significantly affected on blood hematological parameters measured. Serum enzymes showed that activities of aspartate amino transferase did not significantly (P<0.05) differ between all treatments. The activity of alanine amino transferase, total protein and albumin values were significantly (P<0.05) higher with levels 0.75% WTE compared to control. The economical efficiency obtained in rabbits drank 0.25, 0.50 and 0.75% WTE were 152.67, 97.75 and 76.60%, respectively in comparison to 100% of control. Conclusively, most results indicated that rabbits drank 0.25% WTE (2.5 g/100 ml water) had the best performance and economical efficiency. [ABSTRACT FROM AUTHOR]

Context: The antitumor activity of aloin, the active anthraquinone of Aloe juice, against different murine and human tumors has been reported. Objective: In the present study, the impact of repeated aloin treatment at its maximum tolerated dose on serum levels of lipid profile, some elements, iron status and kidney function, compared with doxorubicin (a cardiotoxic anthracycline and inhibitor of erythropoiesis), was assessed. Materials and methods: Rats were treated with a single dose of doxorubicin (30 mg/kg body weight, intraperitoneal) or aloin (50 mg/kg body weight, intramuscular) twice weekly over 2 weeks. Results: Acute doxorubicin treatment elevated serum levels of triacylglycerols (59.90%), total cholesterol (42.29%), cholesteryl esters (54.75%), low density lipoprotein-cholesterol (230.16%), very low density lipoprotein-cholesterol (56.42%), urea (287.53%), and creatinine (85.38%), whereas serum high density lipoprotein-cholesterol, sodium, and calcium levels were reduced (44.61, 9.61, and 9.76%, respectively), as compared with controls. In contrast, aloin treatment showed insignificant changes in all the aforementioned parameters. Both doxorubicin and aloin induced erythropoiesis impairment demonstrated by a reduction in blood hemoglobin concentration. While aloin treatment elevated serum iron level (30.28%), doxorubicin treatment reduced serum levels of iron (51.47%) and percent transferrin saturation (55.21%), and in contrast, increased serum total iron binding capacity (34.85%). The chelating affinities of iron-aloin and -doxorubicin complexes, which contain bidentate iron-binding moieties, have been shown in the infrared spectra. Discussion and conclusion: The non-cardiotoxic effect of aloin treatment was due to its non-atherogenic and iron-chelating activities, which might also contribute in part to its anti-proliferative activity. [ABSTRACT FROM AUTHOR]

In the current study, daily per os administration of propyl paraben (n-propyl-p-hydroxybenzoate) to adult male rats for four consecutive weeks induced severe hepatotoxicity as revealed by the significant elevation in serum marker enzymes along with a significant decrease in serum protein and its fractions. Furthermore, propyl paraben administration disturbed steroid hormones balance by suppressing serum testosterone level, with a concomitant increase in serum estradiol and an ultimate decrease in testosterone/estradiol ratio. Hepatic and testicular toxicity was furtherly attributed to oxidative stress induction, since propyl paraben altered the oxidant/antioxidant balance in both tissues. Signs of toxicity and histopathological changes in the liver and testes were observed by light microscopy of haematoxylin and eosin-stained sections. In conclusion, our data demonstrate the potency of propyl paraben as an endocrine disruptor to induce disturbances in normal steroid balance in adult male rats. In addition, the induced oxidative stress represents a common mechanism of propyl paraben toxicity in hepatic and testicular tissues. [ABSTRACT FROM AUTHOR]

Objective: The present study was undertaken to identify patient populations at high risk for bone metastases (BM) at any time after diagnosis of operable breast cancer. Subjects and methods: A total number of 59 cases with breast cancer after mastectomy was subdivided into two main groups that included 30 patients with radiologically confirmed BM and 29 patients with no bone metastasis (NBM). Patients with NBM were formerly observed for a one-year follow-up interval to monitor the development of bone metastasis (new BM). Parameters included a full blood picture, tumour markers (carcinoembryonic antigen and CA 15.3) and some biochemical markers (vascular endothelial growth factor and zinc levels, as well as tartrate-resistant acid phosphatase and alkaline phosphatase activities). Results: A significant elevation was recorded in carcinoembryonic antigen level and alkaline phosphatase activity, as well as inflammation and vascularisation markers at the time of primary diagnosis in patients with BM, compared with those without BM. CA 15.3 was significantly higher in the new BM group as compared with the other two groups (patients free of bone metastasis [free BM] and BM). According to the likelihood ratio, a panel of single, calculated as well as combined markers was proposed to predict BM within one year in breast cancer patients. Conclusion: Vascularisation and inflammation markers, as well as CA 15.3 are predictive of bone recurrence within one year in breast carcinoma patients. We suggest that in cancer validation studies it is imperative to search for markers that link to the premetastatic process and to determine what type of mechanism is active in each stage. [ABSTRACT FROM AUTHOR]

Aluminium (Al) is a neurotoxic metal that contributes to the progression of several neurodegenerative diseases. The aim of the present study was to evaluate the protective effect of dietary eugenol supplementation against aluminium (Al)- induced cerebral damage in rats. Male Wistar rats were divided into four groups: normal controls, rats fed a diet containing 6,000 μg g-1 eugenol, rats intoxicated daily with aluminium chloride (84 mg kg-1 body weight) p. o. and fed either a basal diet or a eugenol-containing diet. Daily oral administration of Al for four consecutive weeks to rats significantly reduced brain total antioxidant status (TAS) (11.42±0.31 μmol g-1 tissue, p<0.001) with a subsequent significant enhancement of lipid peroxidation (MDA) (32.55±1.68 nmol g-1 tissue, p<0.002). In addition, Al enhanced brain acetylcholinesterase activity (AChE) (46.22±4.90 U mg-1 protein, p<0.001), tumour necrosis factor alpha (TNF-α) (118.72±11.32 pg mg-1 protein, p<0.001), and caspase 3 (Casp-3) (8.77±1.26 ng mg-1 protein, p<0.001) levels, and in contrast significantly suppressed brain-derived neurotrophic factor (BDNF) (82.74±14.53 pg mg-1 protein, p<0.002) and serotonin (5-HT) (1.54±0.12 ng mg-1 tissue, p<0.01) levels. Furthermore, decreased glial fibrillary acidic protein (GFAP) immunostaining was noticed in the striatum of Al-intoxicated rats, compared with untreated controls. On the other hand, co-administration of dietary eugenol with Al intoxication restored brain BDNF (108.76±2.64 pg mg-1 protein) and 5-HT (2.13±0.27 ng mg-1 tissue) to normal levels, enhanced brain TAS (13.43±0.24 μmol g-1 tissue, p<0.05), with a concomitant significant reduction in TNF-α (69.98±4.74 pg mg-1 protein) and Casp-3 (3.80±0.37 ng mg-1 protein) levels (p<0.001), as well as AChE activity (24.50±3.25 U mg-1 protein, p<0.001), and increased striatal GFAP immunoreactivity, compared with Al-treated rats. Histological findings of brain tissues verified biochemical data. In conclusion, eugenol holds potential as a neuroprotective agent through its hydrophobic, antioxidant, and anti-apoptotic properties, as well as its neurotrophic ability against Al-induced brain toxicity in rats.