Oral administration of iron-saturated bovine lactoferrin-loaded ceramic nanocapsules for breast cancer therapy and influence on iron and calcium metabolism

We determined the anticancer efficacy and internalization mechanism of our polymeric-ceramic nanoparticle system (calcium phosphate nanocores, enclosed in biodegradable polymers chitosan and alginate nanocapsules/nanocarriers [ACSC NCs]) loaded with iron-saturated bovine lactoferrin (Fe-bLf) in a breast cancer xenograft model. ACSC-Fe-bLf NCs with an overall size of 322±27.2 nm were synthesized. In vitro internalization and anticancer efficacy were evaluated in the MDA-MB-231 cells using multicellular tumor spheroids, CyQUANT and MTT assays. These NCs were orally delivered in a breast cancer xenograft mice model, and their internalization, cytotoxicity, biodistribution, and anticancer efficacy were evaluated. Chitosan-coated calcium phosphate Fe-bLf NCs effectively (59%, P≤0.005) internalized in a 1-hour period using clathrin-mediated endocytosis (P≤0.05) and energy-mediated pathways (P≤0.05) for internalization; 3.3 mg/mL of ACSC-Fe-bLf NCs completely disintegrated (~130-fold reduction, P≤0.0005) the tumor spheroids in 72 hours and 96 hours. The IC50 values determined for ACSC-Fe-bLf NCs were 1.69 mg/mL at 10 hours and 1.62 mg/mL after 20 hours. We found that Fe-bLf-NCs effectively (P≤0.05) decreased the tumor size (4.8-fold) compared to the void NCs diet and prevented tumor recurrence when compared to intraperitoneal injection of Taxol and Doxorubicin. Receptor gene expression and micro-RNA analysis confirmed upregulation of low-density lipoprotein receptor and transferrin receptor (liver, intestine, and brain). Several micro-RNAs responsible for iron metabolism upregulated with NCs were identified. Taken together, orally delivered Fe-bLf NCs offer enhanced antitumor activity in breast cancer by internalizing via low-density lipoprotein receptor and transferrin receptor and regulating the micro-RNA expression. These NCs also restored the body iron and calcium levels and increased the hematologic counts.

Higher dietary calcium intakes are associated with reduced risks of fractures, cardiovascular events, and mortality: a prospective cohort study of older men and women

The aim of this population-based, prospective cohort study was to investigate long-term associations between dietary calcium intake and fractures, non-fatal cardiovascular disease (CVD), and death from all causes. Participants were from the Melbourne Collaborative Cohort Study, which was established in 1990 to 1994. A total of 41,514 men and women (∼99% aged 40 to 69 years at baseline) were followed up for a mean (SD) of 12 (1.5) years. Primary outcome measures were time to death from all causes (n = 2855), CVD-related deaths (n = 557), cerebrovascular disease-related deaths (n = 139), incident non-fatal CVD (n = 1827), incident stroke events (n = 537), and incident fractures (n = 788). A total of 12,097 participants (aged ≥50 years) were eligible for fracture analysis and 34,468 for non-fatal CVD and mortality analyses. Mortality was ascertained by record linkage to registries. Fractures and CVD were ascertained from interview ∼13 years after baseline. Quartiles of baseline energy-adjusted calcium intake from food were estimated using a food-frequency questionnaire. Hazard ratios (HR) and odds ratios (OR) were calculated for quartiles of dietary calcium intake. Highest and lowest quartiles of energy-adjusted dietary calcium intakes represented unadjusted means (SD) of 1348 (316) mg/d and 473 (91) mg/d, respectively. Overall, there were 788 (10.3%) incident fractures, 1827 (9.0%) incident CVD, and 2855 people (8.6%) died. Comparing the highest with the lowest quartile of calcium intake, for all-cause mortality, the HR was 0.86 (95% confidence interval [CI] 0.76-0.98, ptrend  = 0.01); for non-fatal CVD and stroke, the OR was 0.84 (95% CI 0.70-0.99, ptrend  = 0.04) and 0.69 (95% CI 0.51-0.93, ptrend  = 0.02), respectively; and the OR for fracture was 0.70 (95% CI 0.54-0.92, ptrend  = 0.004). In summary, for older men and women, calcium intakes of up to 1348 (316) mg/d from food were associated with decreased risks for fracture, non-fatal CVD, stroke, and all-cause mortality.

Effect of increasing dietary calcium through supplements and dairy food on body weight and body composition: a meta-analysis of randomised controlled trials

This meta-analysis of randomised controlled trials assessed the effect of Ca on body weight and body composition through supplementation or increasing dairy food intake. Forty-one studies met the inclusion criteria (including fifty-one trial arms; thirty-one with dairy foods (n 2091), twenty with Ca supplements (n 2711). Ca intake was approximately 900 mg/d higher in the supplement groups compared with control. In the dairy group, Ca intake was approximately 1300 mg/d. Ca supplementation did not significantly affect body weight (mean change ( - 0·17, 95 % CI - 0·70, 0·37) kg) or body fat (mean change ( - 0·19, 95 % CI - 0·51, 0·13) kg) compared to control. Similarly, increased dairy food intake did not affect body weight ( - 0·06, 95 % CI - 0·54, 0·43) kg or body fat change ( - 0·36, 95 % CI - 0·80, 0·09) kg compared to control. Sub-analyses revealed that dairy supplementation resulted in no change in body weight (nineteen studies, n 1010) ( - 0·32, 95 % CI - 0·93, 0·30 kg, P= 0·31), but a greater reduction in body fat (thirteen studies, n 564) ( - 0·96, 95 % CI - 1·46, - 0·46 kg, P < 0·001) in the presence of energy restriction over a mean of 4 months compared to control. Increasing dietary Ca intake by 900 mg/d as supplements or increasing dairy intake to approximately 3 servings daily (approximately 1300 mg of Ca/d) is not an effective weight reduction strategy in adults. There is, however, an indication that approximately 3 servings of dairy may facilitate fat loss on weight reduction diets in the short term.

Synchrotron powder diffraction study of cements pastes

 Knowledge of the degree of hydration of cement pastes is critical for determining properties such as the durability of concrete. As part of an integrated study on the prediction of chloride ingress in reinforced concrete, synchrotron Xray powder diffraction was used to estimate the degree of hydration of cement pastes. While for the past 20 years the composition of Portland cement has been determined by Rietveld analysis of X-ray diffraction, nevertheless there are a number of factors, including the amorphous content of the cement and relative proportion of mineral polymorphs present in the initial clinker, whose impact on the analysis are still not completely understood. Analysis of the resulting diffraction patterns indicated enhanced identification of polymorphs of alite, belite, ferrite and aluminate, which are present in the initial unhydrated cement and clinker, as well as improved quantification of hydrated crystalline phases such as calcium hydroxide and ettringite, which are key phases determining the speed of the chemical reactions in cement. In this paper we describe the experience that we have gained in the determination of the degree of hydration of cement pastes. We detail the standards and precautions that we took to characterize production cements and their hydration products.

Comparative microarray analysis identifies commonalities in neuronal injury: evidence for oxidative stress, dysfunction of calcium signalling, and inhibition of autophagy-lysosomal pathway

Mitochondrial dysfunction, ubiquitin-proteasomal system impairment and excitotoxicity occur during the injury and death of neurons in neurodegenerative conditions. The aim of this work was to elucidate the cellular mechanisms that are universally altered by these conditions. Through overlapping expression profiles of rotenone-, lactacystin- and N-methyl-D-aspartate-treated cortical neurons, we have identified three affected biological processes that are commonly affected; oxidative stress, dysfunction of calcium signalling and inhibition of the autophagic-lysosomal pathway. These data provides many opportunities for therapeutic intervention in neurodegenerative conditions, where mitochondrial dysfunction, proteasomal inhibition and excitotoxicity are evident.

Combination of calcium and magnesium ions prevents substrate inhibition and promotes biomass and lipid production in thraustochytrids under higher glycerol concentration

Effect of calcium and magnesium ions was studied in detail in batch mode in shake flask cultures of two fast growing strains of thraustochytrids (Aurantiochytrium sp. DBTIOC-18 and Schizochytrium sp. DBTIOC-1) for biomass and lipid production. These strains were previously isolated from Indian marine biodiversity. Screening of these two strains on different carbon and nitrogen sources revealed the suitability of glycerol over glucose and sodium nitrate over yeast extract for the cultivation of these strains. The presence of higher concentration of glycerol in the medium inhibited the glycerol utilization by the cell thus resulting in lower biomass and lipid production in both the strains. Supplementing media with calcium and magnesium ions promoted glycerol utilization thus resulted in a substantial rise in volumetric production of biomass (55.12 g L-1, 48.12 g L-1), fatty acid for biodiesel (27.14 g L-1, 22.15 g L-1) and docosahexaenoic acid (14.57 g L-1, 10.12 g L-1) with both strains Aurantiochytrium sp. DBTIOC-18 and Schizochytrium sp. DBTIOC-1, respectively. Growth profile study of these two strains showed further improvement in production of biomass, fatty acid for biodiesel and docosahexaenoic acid when cultures were extended up to 7 days. Finding of this work underlines the importance of calcium and magnesium salts in designing new fermentation strategies to prevent substrate inhibition and achieve high cell density culture under high nutrient concentration especially carbon sources.