Low-protein diets supplemented with isoleucine alleviate lipid deposition in broilers through activating 5' adenosine monophosphate-activated protein kinase and janus kinase 2/signal transducer and activator of transcription 3 signaling pathways.

This study aimed to evaluate the effect of isoleucine (Ile) on growth performance, meat quality and lipid metabolism of broilers fed a low-protein diet (LPD). The 396 one-day-old male Cobb broilers were allocated to 4 treatment groups as follows: control diet (CON), LPD, LPD + 0.13% Ile (LPD-LI) and LPD + 0.26% Ile (LPD-HI), with nine replicates of 11 broilers each for 42 d. The Ile increased average daily gain, average daily feed intake, fiber density and the mRNA level of myosin heavy chain (MyHC)-I in breast muscle, and decreased feed to gain ratio, shear force, fiber diameter and the mRNA level of MyHC-IIb in breast muscle, which were impaired by the LPD. Compared to the LPD group, broilers in LPD-LI and LPD-HI groups had lower serum lipid levels, liver fat content, abdominal adipose percentage and mRNA levels of peroxisome proliferator-activated receptor-γ, CCAAT/enhancer binding protein-α, ki-67, topoisomerase II alpha (TOP2A) and thioredoxin-dependent peroxidase 2 in abdominal adipose and liver X receptors-α, sterol regulatory element binding protein 1 (SREBP1), acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) in liver, and higher mRNA levels of peroxisome proliferator activated receptor-α, carnitine palmitoyl-transferase 1 (CPT-1), and acyl-CoA oxidase 1 (ACOX1) in liver, which were equal to the CON levels. A LPD supplemented with Ile decreased enzyme activities of ACC and FAS in liver and glycerol-3-phosphate dehydrogenase and TOP2A in abdominal adipose, and increased enzyme activities of CPT-1 and ACOX1 in liver. Furthermore, Ile supplementation enhanced the mRNA level of leptin receptor and protein levels of phospho-5' adenosine monophosphate-activated protein kinase (AMPK), mechanistic target of rapamycin, ribosomal protein 70 S6 kinase, janus kinase 2 (JAK2), and signal transducer and activator of transcription 3 (STAT3), and decreased the protein level of SREBP1 in the liver of broilers in LPD group. In conclusion, dietary supplementation with Ile to 0.83% could improve growth performance and meat quality and alleviate lipid deposition of broilers fed a LPD through activating AMPK and JAK2/STAT3 signaling pathways.

Chlorogenic acid improves growth performance and intestinal health through autophagy-mediated nuclear factor erythroid 2-related factor 2 pathway in oxidatively stressed broilers induced by dexamethasone.

The effects of chlorogenic acid (CGA) on growth performance, intestinal morphology, antioxidant capacity, and the autophagy-mediated nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in oxidatively stressed broilers were investigated. A total of 400 one-day-old male Cobb broilers were divided randomly into 4 groups using a 2 × 2 factorial arrangement with 2 CGA supplemental levels (0 and 500 mg/kg) and 2 dexamethasone (DEX) challenge levels (0 and 3 mg/kg body weight). All the broilers were injected intraperitoneally with DEX or sterile saline beginning at the age of 15 d for 6 consecutive days. The experiment lasted for 21 d. The CGA increased average daily gain (ADG), villus height, villus height/crypt depth (V/C) value, and the protein expressions of Occludin and ZO-1 in the ileum and decreased the feed:gain (F:G) ratio, which were impaired by the DEX challenge. Superoxide dismutase (SOD), catalase (CAT), gutathione S-transferase (GST), and heme oxygenase-1 (HO-1) activities in the serum and ileum were increased by CGA, whereas protein carboxyl (PCO) level in the serum and ileum, and malondialdehyde (MDA) level in the ileum were decreased of the DEX challenged broilers. The DEX challenge decreased microtubule-associated protein 1 light chain 3 (LC3)-II, Beclin1, and autophagy-related gene (ATG) 7 mRNA expressions, and the LC3-II/LC3-I value and increased LC3-I, cysteinyl aspartate specific proteinase (Caspase)-3 and Caspase-9 mRNA expressions in the ileum, which were improved by CGA. DEX also decreased the protein expressions of Kelch-like ECH-associated protein-1 (Keap1), Nrf2, HO-1, NADPH quinone oxidoreductase-1(NQO-1) and increased sequestosome 1 (p62) in the ileum, which were improved by CGA. Interactions occurred between DEX and CGA for the ADG, F:G ratio, villus height, crypt depth, V/C value, and SOD, CAT, GST, and HO-1 activities, MDA and PCO levels, LC3-II/LC3-I value, and expressions of LC3-I, LC3-II, Beclin1, ATG7, Caspase-3, Caspase-9, Occludin, ZO-1, Keap1, Nrf2, HO-1, NQO-1, and p62. In conclusion, CGA improved the growth performance and intestinal health of oxidatively stressed broilers by activating the autophagy-mediated Nrf2 pathway.

LncRNA BE503655 inhibits osteosarcoma cell proliferation, invasion/migration via Wnt/ß-catenin pathway.

Aim: In previous studies, numerous dysregulated long non-coding RNAs (lncRNAs) were identified by RNA-sequencing (RNA-seq). However, the relationship between lncRNA and osteosarcoma remains unclear. In the present study, the function and mechanism of lncRNA BE503655 were investigated. Methods: Transwell, cell cycle and proliferation were used to evaluate the function of lncRNA BE503655. Real-time PCR and Western blotting were used to detect the expression of lncRNA BE503655 and ß-catenin. Results: LncRNA BE503655 is overexpressed in human osteosarcoma and osteosarcoma cell lines. Knockdown lncRNA BE503655 suppresses cell proliferation, invasion and migration. High expression of BE503655 was significantly related to Enneking stage, distant metastasis and histological grade. Moreover, we also provided evidences that lncRNA BE503655 played its functions dependent on regulation of Wnt/ß-catenin signaling in osteosarcoma. Conclusion: Taken together, we verified the role of lncRNA BE503655 and provided possible mechanism in osteosarcoma. Our study provided new insights into clinical treatment of osteosarcoma and further intervention target.

LncRNA BDNF-AS is associated with the malignant status and regulates cell proliferation and apoptosis in osteosarcoma.

Long non-coding RNA (LncRNA) brain-derived neurotrophic factor antisense (BDNF-AS) has been found to be down-regulated and function in a tumor suppressive role in human cancers. However, the expression status and function of BDNF-AS is still unknown in osteosarcoma (OS). In our study, BDNF-AS expression was found to be decreased in OS tissues and cells. Moreover, BDNF-AS low expression was correlated with advanced Enneking stage, large tumor size and poor prognosis in OS patients. The multivariate analysis suggested low expression of BDNF-AS was an independent unfavorable prognostic factor for overall survival in OS patients. The in vitro studies indicated that BDNF-AS overexpression inhibits OS cell proliferation and promotes cell apoptosis through regulating cleaved caspase-3. In conclusion, BDNF-AS serves as a tumor suppressive lncRNA in OS.