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Cancer response to chemotherapy is regulated not only by intrinsic sensitivity of cancer cells but also by tumor microenvironment. Tumor hypoxia, a condition of low oxygen level in solid tumors, is known to increase the resistance of cancer cells to chemotherapy. Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Due to lack of target in TNBC, chemotherapy is the only approved systemic treatment. We evaluated the effect of hypoxia on chemotherapy resistance in TNBC in a series of in vitro and in vivo experiments. Furthermore, we synthesized the calcium peroxide-modified magnetic nanoparticles (CaO2-MNPs) with the function of oxygen generation to improve and enhance the therapeutic efficiency of doxorubicin treatment in the hypoxia microenvironment of TNBC. The results of gene set enrichment analysis (GSEA) software showed that the hypoxia and autophagy gene sets are significantly enriched in TNBC patients. We found that the chemical hypoxia stabilized the expression of hypoxia-inducible factor 1α (HIF-1α) protein and increased doxorubicin resistance in TNBC cells. https://www.selleckchem.com/products/ml792.html Moreover, hypoxia inhibited the induction of apoptosis and autophagy by doxorubicin. In addition, CaO2-MNPs promoted ubiquitination and protein degradation of HIF-1α. Furthermore, CaO2-MNPs inhibited autophagy and induced apoptosis in TNBC cells. Our animal studies with an orthotopic mouse model showed that CaO2-MNPs in combination with doxorubicin exhibited a stronger tumor-suppressive effect on TNBC, compared to the doxorubicin treatment alone. Our findings suggest that combined with CaO2-MNPs and doxorubicin attenuates HIF-1α expression to improve the efficiency of chemotherapy in TNBC.Pulmonary delivery has high bioavailability, a large surface area for absorption, and limited drug degradation. Particle engineering is important to develop inhalable formulations to improve the therapeutic effect. In our work, the poorly water-soluble meloxicam (MX) was used as an active ingredient, which could be useful for the treatment of non-small cell lung cancer, cystic fibrosis, and chronic obstructive pulmonary disease. We aimed to produce inhalable "nano-in-micro" dry powder inhalers (DPIs) containing MX and additives (poly-vinyl-alcohol, leucine). We targeted the respiratory zone with the microcomposites and reached a higher drug concentration with the nanonized active ingredient. We did the following investigations particle size analysis, morphology, density, interparticular interactions, crystallinity, in vitro dissolution, in vitro permeability, in vitro aerodynamics (Andersen cascade impactor), and in silico aerodynamics (stochastic lung model). We worked out a preparation method by combining wet milling and spray-drying. We produced spherical, 3-4 µm sized particles built up by MX nanoparticles. The increased surface area and amorphization improved the dissolution and diffusion of the MX. The formulations showed appropriate aerodynamical properties 1.5-2.4 µm MMAD and 72-76% fine particle fraction (FPF) values. The in silico measurements proved the deposition in the deeper airways. The samples were suitable for the treatment of local lung diseases.Digitally supported dietary counselling may be helpful in increasing the protein intake in combined exercise and nutritional interventions in community-dwelling older adults. To study the effect of this approach, 212 older adults (72.2 ± 6.3 years) were randomised in three groups control, exercise, or exercise plus dietary counselling. The dietary counselling during the 6-month intervention was a blended approach of face-to-face contacts and videoconferencing, and it was discontinued for a 6-month follow-up. Dietary protein intake, sources, product groups, resulting amino acid intake, and intake per eating occasion were assessed by a 3-day dietary record. The dietary counselling group was able to increase the protein intake by 32% at 6 months, and the intake remained 16% increased at 12 months. Protein intake mainly consisted of animal protein sources dairy products, followed by fish and meat. This resulted in significantly more intake of essential amino acids, including leucine. The protein intake was distributed evenly over the day, resulting in more meals that reached the protein and leucine targets. Digitally supported dietary counselling was effective in increasing protein intake both per meal and per day in a lifestyle intervention in community-dwelling older adults. This was predominantly achieved by consuming more animal protein sources, particularly dairy products, and especially during breakfast and lunch.The pig gastrointestinal tract (GIT) is an open ecosystem in which microorganisms and their host are mutually involved and continually adapt to different factors and problems which may or may not be host dependent or due to the production system. The aim of the present review is to highlight the factors affecting the GIT microbial balance in young pigs, focusing on the pre- and post-weaning phases, to define a road map for improving pig health and the production efficiency of the food chain. Birth and weaning body weight, physiological maturation, colostrum and milk (composition and intake), genetic background, environmental stressors and management practices, antibiotic use and diet composition are considered. Overall, there is a lack of knowledge regarding the effect that some factors, including weaning age, the use of creep feed, the composition of the colostrum and milk and the use of antibiotics, may have on the gut microbiome of piglets. Furthermore, the information on the gut microbiome of piglets is mainly based on the taxonomy description, while there is a lack of knowledge regarding the functional modification of the microbiota, essential for the exploitation of microbiota potential for modulating pig physiology.The live attenuated vaccine strain, SG9R, has been used against fowl typhoid worldwide, but it can revert to the pathogenic smooth strain owing to single nucleotide changes such as nonsense mutations in the rfaJ gene. As SG9R possesses an intact Salmonella plasmid with virulence genes, it exhibits dormant pathogenicity and can cause fowl typhoid in young chicks and stressed or immunocompromised brown egg-laying hens. To tackle these issues, we knocked out the rfaJ gene of SG9R (named Safe-9R) to eliminate the reversion risk and generated detoxified strains of Safe-9R by knocking out lpxL, lpxM, pagP, and phoP/phoQ genes to attenuate the virulence. Among the knockout strains, live ΔlpxL- (Dtx-9RL) and ΔlpxM-9R (Dtx-9RM) strains induced remarkably less expression of inflammatory cytokines in chicken macrophage cells, and oil emulsion (OE) Dtx-9RL did not cause body weight loss in chicks. Live Dtx-9RM exhibited efficacy against field strain challenge in one week without any bacterial re-isolation, while the un-detoxified strains showed the development of severe liver lesions and re-isolation of challenged strains.
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