Parental betaine supplementation promotes gosling growth with epigenetic modulation of IGF gene family in the liver.

Betaine is widely used as a feed additive in the chicken industry to promote laying performance and growth performance, yet it is unknown whether betaine can be used in geese to improve the laying performance of goose breeders and the growth traits of offspring goslings. In this study, laying goose breeders at 39 wk of age were fed basal (Control, CON) or betaine-supplemented diets at low (2.5 g/kg, LBT) or high (5 g/kg, HBT) levels for 7 wk, and the breeder eggs laid in the last week were collected for incubation. Offspring goslings were examined at 35 and 63 d of age. The laying rate tended to be increased (P = 0.065), and the feed efficiency of the breeders was improved by betaine supplementation, while the average daily gain of the offspring goslings was significantly increased (P < 0.05). Concentrations of insulin-like growth factor 2 (IGF-2) in serum and liver were significantly increased in the HBT group (P < 0.05), with age-dependent alterations of serum T3 levels. Concurrently, hepatic mRNA expression of the IGF gene family was significantly increased in goslings derived from betaine-treated breeders (P < 0.05). A higher ratio of proliferating cell nuclear antigen (PCNA)-immunopositive nuclei was found in the liver sections of the HBT group, which was confirmed by significantly upregulated hepatic expression of PCNA mRNA and protein (P < 0.05). Moreover, hepatic expression of thyroxine deiodinase type 1 (Dio1) and thyroid hormone receptor ß (TRß) was also significantly upregulated in goslings of the HBT group (P < 0.05). These changes were associated with significantly higher levels of global DNA 5-mC methylation, together with increased expression of methyl transfer genes (P < 0.05), including betaine-homocysteine methyltransferase (BHMT), glycine N-methyltransferase (GNMT), and DNA (cytosine-5-)-methyltransferase 1 (DNMT1). The promoter regions of IGF-2 genes, as well as the predicted TRß binding site on the IGF-2 gene, were significantly hypomethylated (P < 0.05). These results indicate that gosling growth can be improved by dietary betaine supplementation in goose breeders via epigenetic modulation of the IGF gene family, especially IGF-2, in the liver.

The goose industry plays important roles in economics, cultures, and ecosystems, yet the low laying and growth rates of many indigenous breeds hinders the development of the goose farming. Betaine, an important methyl donor, is commonly used as a feed additive in livestock and poultry to enhance animal growth. Dietary supplementation of betaine in laying hens or gestational sows has been reported to promote the growth of their offspring. Here, we sought to investigate whether and how dietary betaine supplementation affects the growth and development of offspring goslings. In this study, goose breeders, both male and female, were fed a basal diet supplemented respectively with 0, 2.5, or 5 g/kg betaine for 7 wk. Goslings hatched from the breeder eggs of different groups were raised under the same standard condition for assessing the growth performance. Parental betaine increases the growth rate of offspring goslings with decreased DNA methylation on the IGF-2 gene promoter and increased expression of the IGF-2 gene in the liver. These results provide scientific evidence for the inter-generational effect of betaine on gosling growth.

Effect of 12-week shen-based qigong exercise on the residual symptoms of schizophrenia: Study protocol for a single-centre randomised controlled trial.

Introduction: Negative symptoms and cognitive impairment are common residual symptoms of schizophrenia that seriously affect the quality of life and social function of patients. The intervention of residual symptoms is an important part of schizophrenia rehabilitation. Traditional Chinese exercise has been applied as a supplementary rehabilitation method for schizophrenia. However, research on its use and pertinence in the rehabilitation of residual symptoms remains lacking. In this study, we will verify the intervention effect of a new method, namely, shen-based qigong exercise, on the residual symptoms of schizophrenia, in the hopes of finding a safe and effective rehabilitation method for the residual symptoms of schizophrenia. Methods: This is a single-centre randomised controlled trial. A total of 60 schizophrenics who meet the criteria will be randomly divided into the control and intervention groups in accordance with the ratio of 1:1. Conventional drug treatment will remain unchanged in both groups. In this case, the control group will be given daily rehabilitation, whereas the intervention group will be given daily rehabilitation and shen-based qigong exercise intervention. The intervention period will be 12 weeks. The primary outcome will be negative symptoms assessed by the Scale for the Assessment of Negative Symptoms. The secondary outcome will be the global cognitive function assessed by the Repeatable Battery for the Assessment of Neuropsychological Status and event-related potential P300. Other outcomes will include specific cognitive domain (i.e. working memory), quality of life and social function. The results will be measured within 1 week before and after the intervention. Discussion: The results of this study will likely help find an economical and convenient rehabilitation method for the residual symptoms of schizophrenia and, at the same time, may promote the popularisation and application of traditional Chinese exercises and traditional Chinese medicine theories in the treatment of mental diseases. Trial registration: ClinicalTrials.gov registry number: NCT05310955.

Autophagy is involved in the neuroprotective effect of nicotiflorin.

ETHNOPHARMACOLOGICAL RELEVANCE: Nicotiflorin is a flavonoid glycoside derived from the traditional Chinese medicine FlosCarthami, dried petals of Carthamus tinctorius L., and has been confirmed to be a promising novel drug candidate for ischemic stroke. Yet, the exact role of nicotiflorin in cerebral I/R injury is uncharacterized and the possible mechanisms have not been clearly expounded. AIM OF THE STUDY: The present study was designed to determine the effect of nicotiflorin on cerebral ischemia/reperfusion (I/R) injury and its relationship with autophagy. MATERIALS AND METHODS: Middle cerebral artery occlusion (MCAO) in rats and oxygen-glucose deprivation and reintroduction (OGD/R) in SH-SY5Y cells were established in in vivo and in vitro models, respectively. The severity of MCAO was assessed by brain infarct size, neurological scores and survival rate. The severity of OGD/R was evaluated by cell viability, lactate dehydrogenase (LDH) release and cell apoptosis. The level of autophagy was evaluated both in vivo and in vitro. Autophagosomes were observed using transmission electron microscopy and autophagic flux was measured using mRFP-GFP-tandem fluorescent LC3 adenovirus. Autophagy-related proteins (LC3-II/I, SQSTM1, beclin-1, Phospho-mTOR/mTOR) were measured by immunoblot. Autophagy-related mRNA levels (Becn1, Atg7) were detected by Real-Time PCR. Inhibition of autophagy was implemented by 3-Methyladenine (3-MA) or chloroquine in vitro. RESULTS: In vivo, nicotiflorin treatment alleviated brain damage and neurological deficit while it dramatically increased 72 h survival rate in rats. In vitro, nicotiflorin treatment also ameliorated the severity of OGD/R. Moreover, nicotiflorin treatment increased ischemic penumbra autophagy (autophagosomes, BECN1, LC3-II/I ratio, SQSTM1, Phospho-mTOR/mTOR, Atg7). In vitro, nicotiflorin likewise enhanced autophagy and promoted autophagy flux. Furthermore, the blockade of autophagy by 3-MA or chloroquine disabled the efficacic of nicotiflorin in preventing cell damage upon OGD/R insult. CONCLUSION: These findings suggest that autophagy plays a significant role in the protective effect of nicotiflorin against ischemic stroke.

Tauroursodeoxycholic Acid Protects Nucleus Pulposus Cells from Compression-Induced Apoptosis and Necroptosis via Inhibiting Endoplasmic Reticulum Stress.

Tauroursodeoxycholic acid (TUDCA) is a kind of hydrophilic bile acid, which could protect cells from death via inhibiting endoplasmic reticulum (ER) stress. However, the role of TUDCA in compression-induced intervertebral disc degeneration (IVDD) has not been elucidated. Here, we used a previously described device to mimic in vivo compression conditions. NP cells treated with DMSO or TUDCA were exposed to compression. Then, cell viability, morphology, and apoptosis were detected. Furthermore, apoptosis-related proteins and necroptosis markers were detected too. To investigate the specific cytoprotective mechanisms of TUDCA in IVDD, we detected the ER morphology by electron microscopy. In addition, the ER stress of nucleus pulposus (NP) cells was quantitatively evaluated by analyzing the level of ER-stress-associated proteins. Our results revealed that TUDCA could protect NP cells from excessive compression-induced death by reducing the apoptosis and necroptosis. In addition, ER stress is involved in pathogenesis of IVDD induced by excessive compression and plays a detrimental role. TUDCA exerts its protective functions by inhibiting ER stress. In conclusion, TUDCA could protect NP cells from compression-induced death, which suggested that treatment by TUDCA may be a potential method to retard IVDD.