DNA aptamer-conjugated lipid nanoparticle for targeted PTEN mRNA delivery to prostate cancer cells.

The use of messenger RNA (mRNA) as a cancer vaccine and gene therapy requires targeted vehicle delivery to the site of disease. Here, we designed a mRNA-encapsulating lipid nanoparticle (LNP) conjugated with anti-programmed death-ligand 1 (PD-L1) DNA aptamer that delivers mRNA encoding a tumor suppressor gene, namely phosphatase and tensin homolog (PTEN), to castration-resistant prostate cancer (CRPC) cells expressing PD-L1 on the cell surface. The DNA aptamer-conjugated LNP-based mRNA delivery system (Apt-LNP[PTEN mRNA]) mediated efficient mRNA delivery and transfection in CRPC cells than LNPs without targeting ligands.

Mesoporous Silica Particle as an RNA Adsorbent for Facile Purification of In Vitro-Transcribed RNA.

Messenger RNA vaccines against SARS-CoV-2 hold great promise for the treatment of a wide range of diseases by using mRNA as a tool for generating vaccination antigens as well as therapeutic proteins in vivo. Increasing interest in mRNA preparation warrants reliable methods for in vitro transcription (IVT) of mRNA, which must entail the elimination of surplus side products such as immunogenic double-stranded RNA (dsRNA). We developed a facile method for the removal of dsRNA from in vitro transcribed RNA with mesoporous silica particles as RNA adsorbents.

Aptamer-conjugated nano-liposome for immunogenic chemotherapy with reversal of immunosuppression.

Cancer cells have various immune evasion mechanisms that resist the immune cells by reprogramming the tumor microenvironment (TME), such as programmed death-ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase-1 (IDO1) overexpression. One of the approaches to restore antitumor immune response by T-cells is through induction of immunogenic cell death (ICD). Thus, drug carrier containing IDO1 siRNA and ICD inducer would be effective anticancer regimen to modulate the immunosuppressive TME by reversing the IDO1-mediated immunosuppression in a synergistic combination with ICD induction.

Skeletal muscle respiratory capacity is enhanced in rats consuming an obesogenic Western diet.

Obesity-induced lipid oversupply promotes skeletal muscle mitochondrial biogenesis. Previous investigations have utilized extreme high-fat diets (HFD) to induce such mitochondrial perturbations despite their disparity from human obesogenic diets. Here, we evaluate the effects of Western diet (WD)-induced obesity on skeletal muscle mitochondrial function.

The effect of exercise on the skeletal muscle phospholipidome of rats fed a high-fat diet.

The aim of this study was to examine the effect of endurance training on skeletal muscle phospholipid molecular species from high-fat fed rats. Twelve female Sprague-Dawley rats were fed a high-fat diet (78.1% energy).

Effect of L-carnitine supplementation and aerobic training on FABPc content and beta-HAD activity in human skeletal muscle.

Both regular physical exercise and carnitine supplementation exert a role in energy metabolism and may improve endurance capacity. We investigated whether a combination of long-term carnitine ingestion and exercise training reveals any interactive effects on cytosolic fatty acid-binding protein (FABPc) expression and beta-hydroxyacyl CoA dehydrogenase (beta-HAD) activity in human skeletal muscle. Twenty-eight untrained healthy males randomly divided into four experimental groups: a placebo (CON; n = 7), exercise training (ET; n = 7, 40 min session(-1), five times per week at 60% VO2max), carnitine supplementation (CS; n = 7, 4 g day(-1)), and exercise training and carnitine supplementation (CT; n = 7).

Saturated, but not n-6 polyunsaturated, fatty acids induce insulin resistance: role of intramuscular accumulation of lipid metabolites.

Consumption of a Western diet rich in saturated fats is associated with obesity and insulin resistance. In some insulin-resistant phenotypes this is associated with accumulation of skeletal muscle fatty acids. We examined the effects of diets high in saturated fatty acids (Sat) or n-6 polyunsaturated fatty acids (PUFA) on skeletal muscle fatty acid metabolite accumulation and whole-body insulin sensitivity.

Effect of exercise training on muscle glucose transporter 4 protein and intramuscular lipid content in elderly men with impaired glucose tolerance.

This study determined the effects of exercise training on adaptations of skeletal muscle including fibre composition, capillarity, intra-muscular triglyceride concentration (IMTG), as well as glucose transporter 4 protein (GLUT4) and metabolic enzyme activities. Percutaneous muscle biopsies from the vastus lateralis muscle were obtained from non-obese elderly Korean men (n = 10; age range 58-67 years) with impaired glucose tolerance. Subjects performed 12 weeks of endurance exercise training (60-70% of the heart rate reserve).

Postexercise muscle triacylglycerol and glycogen metabolism in obese insulin-resistant zucker rats.

Objective: To determine the impact of insulin resistance and obesity on muscle triacylglycerol (IMTG) and glycogen metabolism during and after prolonged exercise.

Research Methods And Procedures: Female lean (fa/?; N = 40, ZL) and obese insulin-resistant (fa/fa; N = 40, ZO) Zucker rats performed an acute bout of swimming exercise (8 times for 30 minutes) followed by 6 hours of carbohydrate supplementation (CHO) or fasting (FAST). IMTG and glycogen were measured in the extensor digitorum longus (EDL) and red vastus lateralis (RVL) muscles.

Exercise alters the profile of phospholipid molecular species in rat skeletal muscle.

We have determined the effect of two exercise-training intensities on the phospholipid profile of both glycolytic and oxidative muscle fibers of female Sprague-Dawley rats using electrospray-ionization mass spectrometry. Animals were randomly divided into three training groups: control, which performed no exercise training; low-intensity (8 m/min) treadmill running; or high-intensity (28 m/min) treadmill running. All exercise-trained rats ran 1,000 m/session for 4 days/wk for 4 wk and were killed 48 h after the last training bout.

Dietary regulation of fat oxidative gene expression in different skeletal muscle fiber types.

Objective: To determine the effect of a high-fat diet on the expression of genes important for fat oxidation, the protein abundance of the transcription factors peroxisome proliferator-activated receptor (PPAR) isoforms alpha and gamma, and selected enzyme activities in type I and II skeletal muscle.

Research Methods And Procedures: Sprague-Dawley rats consumed either a high-fat (HF: 78% energy, n = 8) or high-carbohydrate (64% energy, n = 8) diet for 8 weeks while remaining sedentary.

Results: The expression of genes important for fat oxidation tended to increase in both type I (soleus) and type II (extensor digitorum longus) fiber types after an HF dietary intervention.

Greater effect of diet than exercise training on the fatty acid profile of rat skeletal muscle.

We determined the interaction of diet and exercise-training intensity on membrane phospholipid fatty acid (FA) composition in skeletal muscle from 36 female Sprague-Dawley rats. Animals were randomly divided into one of two dietary conditions: high-carbohydrate (64.0% carbohydrate by energy, n = 18) or high fat (78.

Effect of training on activation of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase pathways in rat soleus muscle.

1. The effect of a chronic programme of either low- or moderate-to-high-intensity treadmill running on the activation of the extracellular-signal regulated protein kinase (ERK1/2) and the p38 mitogen-activated protein kinase (MAPK) pathways was determined in rat muscle. 2.