Polymeric nanoparticles are designed to transport and deliver nitric oxide (NO) into hepatic stellate cells (HSCs) for the potential treatment of both liver fibrosis and portal hypertension. The nanoparticles, incorporating NO donor molecules (S-nitrosoglutathione compound), are designed for liver delivery, minimizing systemic delivery of NO. The nanoparticles are decorated with vitamin A to specifically target HSCs. We demonstrate, using in vitro and in vivo experiments, that the targeted nanoparticles are taken up specifically by rat primary HSCs and the human HSC cell line accumulating in the liver. When nanoparticles, coated with vitamin A, release NO in liver cells, we find inhibition of collagen I and α-smooth muscle actin (α-SMA), fibrogenic genes associated with activated HSCs expression in primary rat liver and human activated HSCs without any obvious cytotoxic effects. Finally, NO-releasing nanoparticles targeted with vitamin A not only attenuate endothelin-1 (ET-1) which elicites HSC contraction but also acutely alleviates haemodynamic disorders in bile duct-ligated-induced portal hypertension evidenced by decreasing portal pressure (≈20%) and unchanging mean arterial pressure. This study clearly shows, for the first time, the potential for HSC targeted nanoparticle delivery of NO as a treatment for liver diseases with proven efficacy for alleviating both liver fibrosis and portal hypertension.

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The aim of the present work was to investigate the effects of feeding regimens (pasture vs. mixed diet) on meat quality, fatty acids, volatile compounds, and antioxidant properties in lamb meat. In total, 24 lambs were allotted into two feeding regimens at 10.23 kg live weight. Lambs were fed on pasture grass (PG group, n = 12) or mixed diet (M group, n = 12). Longissimus thoracis (LT) muscle samples from the M group had a higher intramuscular fat (IMF) (p < 0.05), pH45minvalue (p < 0.01), and ash (p < 0.05) than the PG group. In contrast, the shear force (p < 0.05), L*(p < 0.05), and b* (p < 0.001) in M group were lower than in PG group. Analyses indicated that PG group contained higher linolenic acid (C18:3n3) and docosatrienoic acid (C22:3n6) (p < 0.05) than the M group. Major volatile compounds in the muscles included hexanal, heptanal, nonanal, octanal, 1‐pentanol, 1‐hexanol, 1‐octen‐3‐ol, and 2,3‐octanedione. The levels of hexanal, nonanal, and 2,3‐octanedione were significantly lower in PG lamb muscle (p < 0.01). In contrast, 1‐pentanol and 1‐hexanol levels were higher in M lamb muscle (p < 0.01). Muscle from PG lamb exhibited higher catalase (CAT) and glutathione peroxidase (GPx) activity (p < 0.05). PG muscle also contained a higher radical‐scavenging ability (RSA; p < 0.001) and cupric‐reducing antioxidant capacity (CUPRAC; p < 0.05). Overall, the improved antioxidant status in PG muscle inhibited lipid peroxidation (aldehydes and ketones), thereby improving the meat quality.

• Adiponectin activates HSC iNOS/NO and SEC eNOS/NO systems. • Adiponectin inhibits HSC proliferation and migration but promotes its apoptosis. • Adiponectin inhibits CCL4-induced liver fibrosis by modulation of liver iNOS/NO. • Adiponectin stimulates HSC iNOS/NO via adipoR2-AMPK-JNK/ErK1/2-NF-κB pathway.

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