ABSTRACT
Lanthanum can reduce absorption of phosphate by forming lanthanum phosphate complexes after oral administration of lanthanum carbonate tablets (FOSRENOL®) in patients. Based on the pH-responsive interaction of phosphate and lanthanum ions, the chitosan coated siRNA-loaded lanthanum phosphate nanoparticles (CS/LaP/siRNA NPs) were prepared for improving cancer treatment, in which polysaccharide chitosan was used as the outer shell to control the excessive growth of lanthanum phosphate complexes, and enable intestinal mucoadhesion. The CS/LaP/siEGFR NPs exhibited significant biological activities in human colorectal cancer HT-29 cells by the synergistic effects of siEGFRs and lanthanum ions, such as downregulation of EGFR and upregulation of miR-34a. Furthermore, significant tumor growth inhibition was observed in both transgenic C57BL/6-ApcMinC/Nju cancer mouse model and AOM/DSS chemically induced orthotopic colorectal cancer mouse model after intestinal instillation administration of CS/LaP/siEGFR NPs. Therefore, the lanthanum-based siRNA delivery system would provide a potential and efficient strategy for the treatment of colorectal cancers.
Subject(s)
Chitosan , Colorectal Neoplasms , Nanoparticles , Animals , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Humans , Lanthanum , Mice , Mice, Inbred C57BL , Phosphates , RNA, Small InterferingABSTRACT
Astragalus polysaccharides (APS) have been shown to possess a variety of biological activities including anti-oxidant and anti-inflammation functions in a number of diseases. However, their function in pulmonary arterial hypertension (PAH) is still unknown. Rats received APS (200[Formula: see text]mg/kg once two days) for 2 weeks after being injected with monocrotaline (MCT; 60[Formula: see text]mg/kg). The pulmonary hemodynamic index, right ventricular hypertrophy, and lung morphological features of the rat models were examined, as well as the NO/eNOS ratio of wet lung and dry lung weight and MPO. A qRT-PCR and p-I[Formula: see text]B was used to assess IL-1[Formula: see text], IL-6 and TNF-[Formula: see text] and WB was used to detect the total I[Formula: see text]B. Based on these measurements, it was found that APS reversed the MCT-induced increase in mean pulmonary arterial pressure (mPAP) (from 32.731[Formula: see text]mmHg to 26.707[Formula: see text]mmHg), decreased pulmonary vascular resistance (PVR) (from 289.021[Formula: see text]mmHg[Formula: see text][Formula: see text] min/L to 246.351[Formula: see text]mmHg[Formula: see text][Formula: see text][Formula: see text]min/L), and reduced right ventricular hypertrophy (from 289.021[Formula: see text]mmHg[Formula: see text][Formula: see text][Formula: see text]min/L to 246.351 mmHg[Formula: see text][Formula: see text][Formula: see text]min/L) ([Formula: see text]0.05). In terms of pulmonary artery remodeling, the WT% and WA% decreased with the addition of APS. In addition, it was found that APS promoted the synthesis of eNOS and the secretion of NO, promoting vasodilation and APS decreased the MCT-induced elevation of MPO, IL-1[Formula: see text], IL-6 and TNF-[Formula: see text], reducing inflammation. Furthermore, APS was able to inhibit the activation of pho-I[Formula: see text]B[Formula: see text]. In couclusion, APS ameliorates MCT-induced pulmonary artery hypertension by inhibiting pulmonary arterial remodeling partially via eNOS/NO and NF-[Formula: see text]B signaling pathways.
Subject(s)
Astragalus Plant , Hypertension, Pulmonary/drug therapy , Monocrotaline/adverse effects , Polysaccharides/pharmacology , Animals , Anti-Inflammatory Agents , Antioxidants , Astragalus Plant/chemistry , Cytokines/metabolism , Disease Models, Animal , Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/metabolism , Male , NF-kappa B/metabolism , Nitric Oxide/metabolism , Nitric Oxide Synthase Type III/metabolism , Polysaccharides/isolation & purification , Rats, Sprague-Dawley , Signal Transduction/drug effects , Vascular Resistance/drug effectsABSTRACT
The effects of different NO3- concentrations (CK, 16 mmol x L(-1) NO3-; T1, 48 mmol x L(-1) NO3-; T2, 96 mmol x L(-1) NO3-; T3, 144 mmol x L(-1) NO3-) on the growth properties and antioxidant enzymes activities of strawberry seedlings were studied by sand culture. The results indicated that the plant height, leaf area, dry matter accumulation and root/shoot ratio of strawberry seedlings in T1, T2 and T3 were significantly decreased compared to the control (CK) after 15 days of treatment. The plant heights in T1, T2 and T3 decreased by 16.1%, 36.8% and 43.9%, and the areas of functional leaf decreased by 19.7%, 34.3% and 47.5% respectively, compared to the control. With the increasing NO3- concentration, the malondialdehyde (MDA), proline, soluble protein content and relative electronic leakage of the strawberry seedlings first increased and then decreased, but all those parameters in T1, T2 and T3 were higher than in the control. The activities of antioxidant enzymes, superoxide dismutase (SOD), peroxidase (POD), ascorbate peroxidase (APX) in both root and leaf, and catalase (CAT) in the root first increased and then decreased, but the CAT activity in the leaf gradually decreased with the increasing NO3 concentration. In T3, the activity of SOD in both root and leaf, APX in the root were lower than in the control. In sum, the osmolytes of strawberry seedlings increased and the plants become weaker under nitrate stress, and some antioxidant enzymes in strawberry seedlings increased at the low level of nitrate stress and decreased at the high level. The strawberry plants were stunted when growing under 48 mmol x L(-1) NO(3-) condition.