Delivery of miR-3529-3p using MnO2 -SiO2 -APTES nanoparticles combined with phototherapy suppresses lung adenocarcinoma progression by targeting HIGD1A.

BACKGROUND: The present study aimed to investigate the function of miR-3529-3p in lung adenocarcinoma and MnO2 -SiO2 -APTES (MSA) as a promising multifunctional delivery agent for lung adenocarcinoma therapy. METHODS: Expression levels of miR-3529-3p were evaluated in lung carcinoma cells and tissues by qRT-PCR. The effects of miR-3529-3p on apoptosis, proliferation, metastasis and neovascularization were assessed by CCK-8, FACS, transwell and wound healing assays, tube formation and xenografts experiments. Luciferase reporter assays, western blot, qRT-PCR and mitochondrial complex assay were used to determine the targeting relationship between miR-3529-3p and hypoxia-inducible gene domain family member 1A (HIGD1A). MSA was fabricated using MnO2 nanoflowers, and its heating curves, temperature curves, IC50, and delivery efficiency were examined. The hypoxia and reactive oxygen species (ROS) production was investigated by nitro reductase probing, DCFH-DA staining and FACS. RESULTS: MiR-3529-3p expression was reduced in lung carcinoma tissues and cells. Transfection of miR-3529-3p could promote apoptosis and suppress cell proliferation, migration and angiogenesis. As a target of miR-3529-3p, HIGD1A expression was downregulated, through which miR-3529-3p could disrupt the activities of complexes III and IV of the respiratory chain. The multifunctional nanoparticle MSA could not only efficiently deliver miR-3529-3p into cells, but also enhance the antitumor function of miR-3529-3p. The underlying mechanism may be that MSA alleviates hypoxia and has synergistic effects in cellular ROS promotion with miR-3529-3p. CONCLUSIONS: Our results establish the antioncogenic role of miR-3529-3p, and demonstrate that miR-3529-3p delivered by MSA has enhanced tumor suppressive effects, probably through elevating ROS production and thermogenesis.

Maternal Chronic Folate Supplementation Ameliorates Behavior Disorders Induced by Prenatal High-Fat Diet Through Methylation Alteration of BDNF and Grin2b in Offspring Hippocampus.

SCOPE: Maternal consumption of a high-fat diet (HFD) during pregnancy increases the risk of behavioral problems. Folate plays an important role in neuroplasticity and the preservation of neuronal integrity. This study aims at determining the influence of diets supplemented with folate on offspring behavior, and the mechanisms involved. METHODS AND RESULTS: Female mice were fed a control diet, an HFD, control diet supplemented with folate, or an HFD supplemented with folate for 5 weeks before mating. Open field task and elevated plus maze are used to evaluate the offspring behaviors. Results showed that offspring cognitive performance and anxiety-related behaviors, including those related to open field exploration and elevated plus maze, were significantly improved when dams were treated with folate in pregnancy. Moreover, the maternal folate supplement decreased BDNF and Grin2b methylation and upregulated their expressions in the brain of offspring, which were associated with decreasing the expression of DNA methyltransferases compared with those dams were treated only HFD in pregnancy. CONCLUSION: Maternal folate supplementation ameliorates behavior disorders induced by prenatal high-fat diet. The beneficial effects were associated with methylation and expression alteration of BDNF and Grin2b genes.

Protective effects of maternal methyl donor supplementation on adult offspring of high fat diet-fed dams.

Obesity has become a global public health problem associated with metabolic dysfunction and chronic disorders. It has been shown that the risk of obesity and the DNA methylation profiles of the offspring can be affected by maternal nutrition, such as high-fat diet (HFD) consumption. The aim of this study was to investigate whether metabolic dysregulation and physiological abnormalities in offspring caused by maternal HFD can be alleviated by the treatment of methyl donors during pregnancy and lactation of dams. Female C57BL/6 mice were assigned to specific groups and given different nutrients (control diet, Control+Met, HFD and HFD+Met) throughout gestation and lactation. Offspring of each group were weaned onto a control diet at 3 weeks of age. Physiological (weight gain and adipose composition) and metabolic (plasma biochemical analyses) outcomes were assessed in male and female adult offspring. Expression and DNA methylation profiles of obesogenic-related genes including PPAR γ, fatty acid synthase, leptin and adiponectin were also detected in visceral fat of offspring. The results showed that dietary supplementation with methyl donors can prevent the adverse effects of maternal HFD on offspring. Changes in the expression and DNA methylation of obesogenic-related genes indicated that epigenetic regulation may contribute to the effects of maternal dietary factors on offspring outcomes.

Irradiation-mediated carbon nanotubes' use in cancer therapy.

Anticancer drugs such as biological therapeutic proteins and peptides are used for treatment of a variety of tumors. However, their wider use has been hindered by their poor bioavailability and the uncontrollable sites of action in vivo. Cancer nano-therapeutics is rapidly progressing, which is being applied for solving some limitations of conventional drug delivery systems. To improve the bio-distribution of anticancer drugs, carbon nanotubes have been used as one of the most effective drug carriers. This review discusses the carbon nanotubes-mediated methods for the delivery of anticancer drugs, with emphasis on the radiation-induced drug-targeted releasing and selective photo-thermal cancer therapy.

Aged black garlic extract induces inhibition of gastric cancer cell growth in vitro and in vivo.

There is mounting evidence that garlic extracts possess significant anticancer actions. However, no studies have been reported on the effects of aged black garlic extracts (ABGE) on gastric cancer in vitro or in vivo. To examine the potential action of ABGE against gastric cancer, the present study evaluated its effect on the inhibition of cell proliferation and induction of apoptosis in SGC-7901 human gastric cancer cells. Additionally, we performed an in vivo study by inoculating the murine foregastric carcinoma cell line in Kunming mice and treating them with various doses of ABGE (0, 200, 400 and 800 mg/kg, intraperitoneally) for 2 weeks. Dose-dependent apoptosis was detected in ABGE-treated cells in in vitro studies. In tumor-bearing mice, significant antitumor effects of ABGE were observed, such as growth inhibition of inoculated tumors. Further investigation of serum superoxide dismutases, glutathione peroxidase, interleukin-2 and the increased indices of spleen and thymus indicated that the anticancer action of ABGE may be partly due to its antioxidant and immunomodulative effects.