The Effects of Milk Protein Polymorphisms on Milk Components and Cheese-Producing Ability

Abstract A Total of 2005 first lactation Holstein-Friesian cows with known 305-d lactation yield for milk, fat, and protein were available. For each cow, genotypes for α s1 -casein, β-casein, κ-casein, and β-lactoglobulin were known. It appears that the milk protein variants α s1 -casein, β-casein, and κ-casein may not be segregating independently. Effects of genetic variants of milk proteins on estimated individual Parmesan cheese yields were investigated. The relationships of the genetic variants of milk proteins to total lactation milk yield, fat yield, protein yield, fat percentage, and protein percentage were also investigated. Least squares analysis of the data indicated that α s1 -casein genotype significantly influenced milk yield, fat yield, and protein yield with the highest yields obtained for the genotype BB . Cheese yield on a fixed amount of milk and fat percentage were significantly related to β-lactoglobulin genotype with the highest estimates obtained for BB . Protein percentage was influenced by α s1 -casein and κ-casein, with the genotypes BC and BB , respectively, having the highest percentages. Significantly higher lactation cheese yields were estimated with α s1 -casein genotype BB . Using the prediction equation to estimate cheese yield (on data from another study), it was found that differences in Parmesan cheese yield from milk of either κ-casein genotype AA or BB were greater than expected based on composition. Differences in salted curd yield from another study using milk of either β-lactoglobulin genotype AA or BB were also greater than expected

3D-Printed Lipid Mesophases for the Treatment of Chronic Liver Disease

Although lipid-based formulations are an attractive approach for enhancing the oral bioavailability of lipophilic drugs, their addition into solid oral dosage forms has been proven challenging due to their high viscosity and heat sensitivity. Therefore, unlike the traditional tableting process, this study employed semi-solid extrusion 3D-printing to produce-at room temperature-gastro-resistant printlets containing a high percentage of bioactive lipids for the effective delivery of lipophilic drugs through self-emulsification. The bio-compatible lipidic mesophase ink, owing to a tunable 3D nanostructure, is employed as a starting material to produce printlets via additive manufacturing. An active lipid mixture - with antifibrotic properties - is blended with the antioxidant vitamin E and water, and the ink printability is optimized by carefully tailoring its composition, and thus its phase identity. The obtained printlets disintegrated upon contact with intestinal fluids forming colloidal structures that enhanced the solubility of a poorly water-soluble drug. The printlets exhibited antifibrotic activity on human hepatic stellate cells, LX-2, suggesting that the generated self-emulsified colloidal structures made both the fibrosis-resolving bioactive excipients and the drug promptly available, enhancing their cell uptake and, in turn, their therapeutic activity.Lipidic mesophases are employed as starting material to produce gastro-resistant oral dosage forms via 3Dprinting. The formulation contains a high percentage of bioactive lipids and it is suitable for the effective delivery of lipophilic drugs through self-emulsification. Indeed, upon contact with intestinal fluids printlets disintegrate, forming colloidal structures that enhance the bioavailability of the drug and its therapeutic activity

Antimicrobial Nanoplexes meet Model Bacterial Membranes: the key role of Cardiolipin

Antimicrobial resistance to traditional antibiotics is a crucial challenge of medical research. Oligonucleotide therapeutics, such as antisense or Transcription Factor Decoys (TFDs), have the potential to circumvent current resistance mechanisms by acting on novel targets. However, their full translation into clinical application requires efficient delivery strategies and fundamental comprehension of their interaction with target bacterial cells. To address these points, we employed a novel cationic bolaamphiphile that binds TFDs with high affinity to form self-assembled complexes (nanoplexes). Confocal microscopy revealed that nanoplexes efficiently transfect bacterial cells, consistently with biological efficacy on animal models. To understand the factors affecting the delivery process, liposomes with varying compositions, taken as model synthetic bilayers, were challenged with nanoplexes and investigated with Scattering and Fluorescence techniques. Thanks to the combination of results on bacteria and synthetic membrane models we demonstrate for the first time that the prokaryotic-enriched anionic lipid Cardiolipin (CL) plays a key-role in the TFDs delivery to bacteria. Moreover, we can hypothesize an overall TFD delivery mechanism, where bacterial membrane reorganization with permeability increase and release of the TFD from the nanoplexes are the main factors. These results will be of great benefit to boost the development of oligonucleotides-based antimicrobials of superior efficacy

Temperature-triggered in situ forming lipid mesophase gel for local treatment of ulcerative colitis

Ulcerative colitis is a chronic inflammatory bowel disease that strongly affects patient quality of life. Side effects of current therapies necessitate new treatment strategies that maximise the drug concentration at the site of inflammation, while minimizing systemic exposure. Capitalizing on the biocompatible and biodegradable structure of lipid mesophases, we present a temperature-triggered in situ forming lipid gel for topical treatment of colitis. We show that the gel is versatile and can host and release drugs of different polarities, including tofacitinib and tacrolimus, in a sustained manner. Further, we demonstrate its adherence to the colonic wall for at least 6 h, thus preventing leakage and improving drug bioavailability. Importantly, we find that loading known colitis treatment drugs into the temperature-triggered gel improves animal health in two mouse models of acute colitis. Overall, our temperature-triggered gel may prove beneficial in ameliorating colitis and decreasing adverse effects associated with systemic application of immunosuppressive treatments

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Associação de SNPs nos genes para κ-caseína e β-lactoglobulina com curvas de lactação em cabras leiteiras

O objetivo deste trabalho foi identificar o modelo com melhor ajuste aos dados de produção de leite, gordura, proteína e sólidos totais para cabras leiteiras, bem como associar polimorfismos de nucleotídeo único (SNPs) nos genes para κ-caseína (κ-CSN3) e β-lactoglobulina (β-LG) aos parâmetros das curvas de produção e qualidade do leite. Foram avaliados 4.160 registros de produção de leite, gordura, proteína e sólidos totais de cabras das raças Alpina, Saanen e mestiça, no Estado de Antioquia, na Colômbia. Os modelos não lineares com melhor ajuste à estrutura dos dados foram os de Nelder, para produção de leite, e de Cappio-Borlino, para qualidade do leite. As análises de associação mostraram efeito significativo do SNP κ-CSN3 sobre o pico de produção, a produção inicial e a persistência das características qualitativas do leite. Já o SNP β-LG apresentou efeito significativo sobre os picos de produção de leite e gordura, e sobre o tempo necessário para atingir o pico de produção de proteína. A identificação e a estimação da influência dos marcadores SNP avaliados sobre as curvas de lactação e a qualidade do leite podem contribuir para a seleção de caprinos leiteiros