Inhibitory effect of butylphthalide on apoptosis of hippocampal neurons in Alzheimer disease rats via SIRT1/NF-κB signaling pathway

AIM: To investigate the effect of butylphthalide on apoptosis of hippocampal neurons in Alzheimer disease (AD) rats via SIRT1/NF-κB signaling pathway and its mechanism. METHODS: AD rat model was established by intragastric administration of AlCl₃ and intraperitoneal injection of D-galactose. After treated with butylphthalide at 25 mg/kg (low dose), 50 mg/kg (medium dose) and 100 mg/kg (high dose), the effects of butylphthalide on the morphology of hippocampal neurons, apoptosis rate, and the protein levels of Bcl-2, Bax, cleaved caspase-3 and the SIRT1/NF-κB signaling pathway associated proteins were determined by HE staining, flow cytometry and Western blot, respectively. After treated with SIRT1 agonist SRT1720 and inhibitor sirtinol, the role of SIRT1/NF-κB signaling pathway in hippocampal neuronal apoptosis was observed. On the basis of giving 50 mg/kg butylphthalide, sirtinol was administered, and the effect of butylphthalide on neuronal apoptosis regulated by SIRT1/NF-κB signaling pathway was evaluated. RESULTS: The morphology of hippocampal neurons in the AD rats were improved, the apoptosis rate of hippocampal neurons and the protein levels of Bax and cleaved caspase-3 were inhibited, and the protein levels of Bcl-2 and the activation of SIRT1/NF-κB signaling pathway were promoted by butylphthalide significantly (P<0.05). The protein expression of Bcl-2 and the activation of SIRT1/NF-κB signaling pathway were promoted, and the apoptosis of hippocampal neurons and the protein levels of Bax and cleaved caspase-3 were inhibited by SRT1720 remarkably (P<0.05), whereas the effect of sirtinol was contrary to that of SRT1720. After sirtinol treatment, the inhibitory effect of butylphthalide on apoptosis of hippocampal neurons, the protein levels of Bax and cleaved caspase-3, and the promotion of Bcl-2 protein expression in hippocampal neurons were markedly weakened (P<0.05). CONCLUSION: Butylphthalide inhibits the apoptosis of hippocampal neurons in the AD rats by down-regulating the protein expression of Bax and cleaved caspase-3, and up-regulating the protein expression of Bcl-2 through activating SIRT1/NF-κB signaling pathway.     

Dietary histidine requirement of juvenile blunt snout bream (Megalobrama amblycephala)

An eight‐week feeding trial was conducted to determine the dietary histidine requirement of juvenile blunt snout bream. The results showed that final body weight, weight gain rate and specific growth rate significantly increased with increasing dietary histidine levels up to 9.9 g/kg (p < .05) and decreased gradually thereafter, while feed conversion ratio showed a converse trend. The survival rate, condition factor, viscerosomatic and hepatosomatic index were not significantly affected by the graded dietary histidine levels (p > .05). About 9.9 g/kg dietary histidine level significantly improved whole‐body protein and lowered moisture content. The contents of plasma total protein, cholesterol, urea and triglyceride levels were not significantly affected by dietary histidine levels. About 9.9 g/kg dietary histidine level significantly upregulated target of rapamycin and insulin‐like growth factor mRNA levels (p < .05), and 12.1 g/kg and 14.2 g/kg dietary histidine levels significantly upregulated eukaryotic translation initiation factor 4E‐binding protein 2 and ribosomal protein S6 kinase‐polypeptide 1 mRNA levels (p < .05). Based on second‐degree polynomial regression analysis of weight gain rate, and specific growth rate against dietary histidine levels, the dietary histidine requirement for juvenile blunt snout bream was estimated to be 11.2 g/kg of diet, corresponding to 36.1 g/kg of dietary protein.     

Changes in phenolic content,composition, and antioxidant activity of blood oranges during cold and on-tree storage

Citrus fruits are rich in phenolic compounds that possess several health benefits. However, few studies have focused on the changes in phenolic compounds in citrus fruits during postharvest storage. This study dynamically monitored the phenolic content, components and antioxidant activity of ‘Tarocco’ blood oranges during a period of 12-week cold storage and on-tree storage, respectively. We investigated the alteration mechanism of phenolic compounds in blood oranges by evaluating phenylpropanoid pathway-related enzyme activities and gene expression. Results showed that flavanones were the main phenolic compounds in blood oranges. Both storage methods mainly stimulated the accumulation of phenolic acids to improve total phenolic content, which reached the maximum at week 12. Nonetheless, blood oranges had a higher phenolic content and antioxidant activity under on-tree storage than cold storage. Furthermore, the enzyme activities and gene expression of the phenylpropanoid pathway demonstrated that the accumulation of phenolics in blood oranges during storage was highly related to the activation of the phenylpropanoid pathway. These results demonstrate that on-tree storage is a potential approach for extending the supply period of blood orange from the perspective of phenolic compounds.     

硒对奶牛乳腺炎的调节作用及抗炎机制

奶牛乳腺炎在临产和泌乳期奶牛中发病率较高,严重影响乳腺健康和牛奶生产,对世界范围内的奶牛业造成重大经济损失。微量元素硒可降低奶牛乳腺炎的发病率和严重程度。本文从硒与奶牛乳腺炎的关系、硒在炎症中对先天性免疫和获得性免疫的调节作用以及硒对炎症相关信号转导机制的调控等几个方面进行了综述,为通过饲粮补硒以改善奶牛乳腺健康提供理论支持。     

Suppression of mel18 enhances differentiation of acute myeloid leukemia cell line HL60 induced by cinnamaldehyde

AIM: To investigate the effect of suppression of mel18 gene on the differentiation of human acute myeloid leukemia cell line HL60 induced by cinnamaldehyde (CA). METHODS: HL60 cells were treated with low concentration of CA or all-trans retinoic acid (ATRA). shRNAmel18 vector and shRNALuc control vector were employed to package lentiviruses which were then used to infect HL60 cells. The virus-infected HL60 cells were treated with low concentration of CA, and ATRA was used as a positive control of differentiation-inducing agent. The differentiation markers on the cell surface and cell cycle of virus-infected HL60 cells were analyzed by flow cytometry. Western blot was used to determine the expression of MEL18, cyclin D1 and p27, as well as the phosphorylation level of Akt. RESULTS: Low concentration of CA and ATRA increased the expression of granulocytic differentiation marker CD11b on the HL60 cells, with the decreased expression of MEL18 in the HL60 cells. The expression of MEL18 decreased in shmel18 virus-infected HL60 cells (shmel18-HL60 cells), but did not change in shLuc-HL60 cells. The expression of CD11b on shmel18-HL60 cells increased with G₁-phase arrest, which went even higher after treatment with CA. The phosphorylation level of Akt and the expression of cyclin D1 decreased in shmel18-HL60 cells with the increase in the expression of p27. CONCLUSION: Inhibition of mel18 gene leads HL60 cell granulocytic differentiation. mel18 gene may affect the differentiation of HL60 cells by regulating cyclin D1 and p27 via PI3K/Akt signaling pathway. PI3K/Akt signaling pathway is also involved in CA-induced differentiation of HL60 cells by suppressing mel18 gene expression.     

Okadaic Acid: A Tool to Study the Hippo Pathway

Mammalian Ste20-like kinases 1 and 2 (MST1 and MST2) are activated in NIH3T3 cells exposed to okadaic acid. The Hippo pathway is a newly emerging signaling that functions as a tumor suppressor. MST1 and MST2 work as core kinases of the Hippo pathway and their activities depend on the autophosphorylation, which is negatively regulated by protein phosphatase 2A (PP2A). Okadaic acid has been frequently used to enhance the phosphorylation of MST1 and MST2 and to trigger the activation of the Hippo pathway. However other components of the Hippo pathway could also be targets of okadaic acid. In this review we first briefly summarize the molecular architecture of the Hippo pathway for the reference of researchers outside the field. We explain how MST kinases are regulated by PP2A and how okadaic acid activates MST2. Thereafter we discuss which components of the Hippo pathway are candidate substrates of protein phosphatases and which points we need to consider in the usage of okadaic acid to study the Hippo pathway.     

Hippo通路及Wwtr1基因的研究进展

Hippo信号通路是在果蝇中发现的,能够调控器官大小,其功能异常会导致肿瘤发生。对Hippo通路及其上游调控因子进行了综述,并对其与其他信号途径之间的关联也进行了介绍。最后,重点阐述了Wwtr1基因的一些生物学功能和研究进展。     

HBx modulates apoptosis by activating JAK2/STAT3 signaling pathway in human renal proximal tubular epithelial cells

AIM: To investigate the correlation of hepatitis B virus X protein (HBx) with renal tubular epithelial cell apoptosis in hepatitis B virus-associated glomerulonephritis (HBVGN) and the possible signaling mechanism. METHODS: The activation of JAK2/STAT3 signal pathway and the expression of apoptosis-related proteins in human kindey proximal tubular epithelial cells (HK-2 cells) were determined by Western blotting after transfection with HBx eukaryotic expression vector. The cell proliferation was observed by CCK-8 assay. The cell apoptosis was analyzed by the imaging of HO33342 staining, transmission electron microscopy and flow cytometry with Annexin V/PI double staining. RESULTS: After transfection of the target gene HBx, the expression levels of both p-JAK2 and p-STAT3 were significantly increased. At the same time, the cell proliferation was obviously inhibited, and the apoptotic rate was increased. After incubation with AG490, the JAK2/STAT3 signal pathway was partially blocked, and the cell apoptosis induced by HBx was reduced. CONCLUSION：HBx up-regulates the activation of JAK2/STAT3 signal pathway to induce renal tubular epithelial cell apoptosis, which is possibly involved in the pathogenic mechanism that HBV directly damages nephridial tissue.     

Research Progress on Propionate Application in Ruminant

Propionate is a kind of new,efficient and safe additive with the functions of anti-mildew,anticorrosion and treatment of diseases,which is widely used in feed processing industry. Propionate is decomposed into propionic acid and mineral elements in the rumen, and propionic acid is the main active ingredient. Propionate can promote rumen development,regulate blood glucose,maintain energy balance,therefore,it has been used to treat ketosis in practice production. At present,the propionate has been studied mostly at the rumen infusion stage,and in vitro experiments are focused on the liver gluconeogenesis pathway,which revolves around energy metabolism. But there are a few researches about the effects of propionate on production performance and fermentation. With the development of study of short chain fatty acids in the medical field,it brings a new opportunity for its development in husbandry. Whether propionate has the ability to promote rumen development, alleviate inflammation and enhance immunity needed to be further explored and verified. This paper mainly introduces the metabolic pathway and the mechanism of propionate and its application value in ruminant animal nutrition,combined with the production performance and maintain health,in order to reveal its potential value and provides scientific basis for its application in ruminant.