Maternal physical activity prevents the overexpression of hypoxia-inducible factor 1-α and cardiorespiratory dysfunction in protein malnourished rats.

Maternal physical activity attenuates cardiorespiratory dysfunctions and transcriptional alterations presented by the carotid body (CB) of rats. Rats performed physical activity and were classified as inactive/active. During gestation and lactation, mothers received either normoprotein (NP-17% protein) or low-protein diet (LP-8% protein). In offspring, biochemical serum levels, respiratory parameters, cardiovascular parameters and the mRNA expression of hypoxia-inducible factor 1-alpha (HIF-1α), tyrosine hydroxylase (TH) and purinergic receptors were evaluate. LP-inactive pups presented lower RF from 1st to 14th days old, and higher RF at 30 days than did NP-inactive and NP-active pups. LP-inactive pups presented with reduced serum protein, albumin, cholesterol and triglycerides levels and an increased fasting glucose level compared to those of NP-inactive and NP-active groups. LP and LP-inactive animals showed an increase in the cardiac variability at the Low-Frequency bands, suggesting a major influence of sympathetic nervous activity. In mRNA analyses, LP-inactive animals showed increased HIF-1α expression and similar expression of TH and purinergic receptors in the CB compared to those of NP groups. All these changes observed in LP-inactive pups were reversed in the pups of active mothers (LP-active). Maternal physical activity is able to attenuate the metabolic, cardiorespiratory and HIF-1α transcription changes induced by protein malnutrition.

Induction of cancer cell death by apoptosis and slow release of 5-fluoracil from metal-organic frameworks Cu-BTC.

This study aimed to evaluate the mechanism associated with cytotoxic activity displayed by the drug 5-fluorouracil incorporated in Cu-BTC MOF and its slow delivery from the Cu-BTC MOF. Structural characterization encompasses elemental analysis (CHNS), differential scanning calorimetry (DSC), thermogravimetric analysis (TG/DTG), Fournier transform infrared (FIT-IR) and X-ray diffraction (XRD) was performed to verify the process of association between the drug 5-FU and Cu-BTC MOF. Flow cytometry was done to indicate that apoptosis is the mechanism responsible for the cell death. The release profile of the drug 5-FU from Cu-BTC MOF for 48 hours was obeisant. Also, the anti-inflammatory activity was evaluated by the peritonitis testing and the production of nitric oxide and pro-inflammatory cytokines were measured. The chemical characterization of the material indicated the presence of drug associated with the coordination network in a proportion of 0.82 g 5-FU per 1.0 g of Cu-BTC MOF. The cytotoxic tests were carried out against four cell lines: NCI-H292, MCF-7, HT29 and HL60. The Cu-BTC MOF associated drug was extremely cytotoxic against the human breast cancer adenocarcinoma (MCF-7) cell line and against human acute promyelocytic leukemia cells (HL60), cancer cells were killed by apoptosis mechanisms. The drug demonstrated a slow release profile where 82% of the drug was released in 48 hours. The results indicated that the drug incorporated in Cu-BTC MOF decreased significantly the number of leukocytes in the peritoneal cavity of rodents as well as reduced levels of cytokines and nitric oxide production.