Role of intestinal microbiota-farnesoid X receptor axis in metabolic diseases

Intestinal microbiota is associated with metabolic diseases such as obesity, nonalcoholic fatty liver disease and insulin resistance. Farnesoid X receptor (FXR), also known as bile acid receptor, is a typical nuclear receptor, which is involved in the regulation of bile acid and glycolipid metabolism. Intestinal microbiota regulates FXR activity by affecting bile acid composition, where bile acid hydrolase plays an important role. Recent studies have found that intestinal microbiota affects the development of metabolic diseases through regulating the FXR, and the intestinal microbiota-FXR axis may be an ideal drug target for metabolic diseases.     

Research progress and important scientific issues of organ fibrosis

Organ fibrosis is a common pathogenetic change of parenchymal organs under chronic conditions, characterized by increased fibrous connective tissues and reduced parenchymal cells. The essence of renal fibrosis is the "repair of scars" after renal tissue damage. It involves a loss of renal parenchyma cells, activation of myofibroblasts, deposition of extracellular matrix, imbalance of metabolism and abnormal interactions with organs. Hepatic fibrosis is a kind of repair response induced by various chronic hepatic diseases, including viral hepatitis and metabolic liver disease, and it is the common pathological basis of end-stage hepatic disease. Pulmonary fibrosis is a progressive and fatal inflammatory interstitial lung disease, characterized by inflammatory destruction and extracellular matrix deposition. Myocardial fibrosis is a process of pathological repair after a variety of injuries caused by hypertension, hypertrophic cardiomyopathy, viral cardiomyopathy, valve disorders, myocardial ischemia, diabetes, obesity and other metabolic abnormalities. Organ fibrosis indicates some common pathogenesis, but the exact mechanisms differ from organs and still need further investigation to identify biomarkers for early diagnosis and to devise drugs specifically for fibrosis. This article comprehensively summarizes the recent developments in organ fibrosis over the last 3 years, including underlying mechanisms and urgent scientific issues remained.     

Anthocyanins attenuates hepatic fibrosis and inflammation in non-alcoho-lic fatty liver disease mice

AIM:To explore the therapeutic effect of anthocyanins from Fructus Acanthophorae on high-fat diet-induced non-alcoholic fatty liver disease (NAFLD) in mice and the potential mechanism. METHODS:NAFLD mouse model was established by high-fat diet, and interferred with anthocyanins. The liver weight, and serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), total cholesterol (TC) and low-density li-poprotein cholesterol (LDL-C) were measured. The liver tissues were staining with HE, Oil Red O and Masson's trichrome. The protein levels of inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6 and IL-10 in the liver tissues were determined by Western blot. The liver macrophage, white blood cell and mononuclear cell infiltration was detected by immunohistochemical method. The chemokines CCL7 and MCP-1 were also measured by immunohistochemical method. RESULTS:Anthocyanins significantly inhibited the increases in the liver weight, ALT, AST, TG, TC and LDL-C induced by high-fat diet. Anthocyanins attenuated the liver fibrosis and inflammatory cell infiltration caused by high-fat diet, and reduced the levels of inflammatory factors TNF-α, IL-1β, IL-6, IL-10 and inflammatory chemokines CCL7 and MCP-1 in the liver tissues. CONCLUSION:Anthocyanins significantly alleviate non-alcoholic fatty liver disease caused by high-fat diet though reducing inflammatory factors, inflammatory cell infiltration and inflammatory chemokines.     

Advance in biological properties of IL-38 and its role in pulmonary diseases

Interleukin-38 （IL-38） is the most recently discovered cytokine of the IL-1 family and is an IL-36 receptor inhibitor. IL-38 is mainly expressed in human immune organs and associated with a variety of diseases. In the process of apoptosis and necrosis caused by injury or inflammation， researchers have studied quiet a lot about the kinase， cleavage sites， activity regulatory mechanism， signal transduction ligand， transduction mode and potential receptors of IL-38， but many mechanisms are still unknown. This article reviews the role of IL-38 in the pathogenesis and progression of lung tumors， asthma and interstitial lung disease. We also discussed the role of IL-38 in the treatment of these diseases， the possible relationship between IL-38 and tuberculosis， and the direction of future studies on the mechanism of IL-38 action.     

枇杷花发育进程中氨基酸和碳水化合物代谢的变化

为研究影响枇杷（Eriobotrya japonica Lindl.‘Ninghaibai’）花的发育相关代谢机制，以花芽生理分化期、花芽形态分化期、花穗发育期、小花发育期和开花期这 5 个阶段的当年生春梢上顶芽、花芽或花穗为试验材料，采用 GC–MS 技术检测其代谢物质，并将 5 个阶段的差异代谢物质进行统计和归类，筛选出了相关性最高的代谢通路。此外，测定其可溶性糖、可溶性蛋白、淀粉含量以及 C/N 比，分析各营养物质在花不同发育阶段的变化。在整个发育进程中共检测出 430 种代谢物，氨基酸代谢和碳水化合物代谢是两个变化最显著的代谢通路，而小花发育期是代谢最为旺盛的阶段。可溶性糖、可溶性蛋白、淀粉含量以及 C/N 比的变化趋势与代谢组表型结果一致，C/N 比是决定花发育进程的重要因素之一。     

不同低温处理对黄瓜子叶极性脂组成的影响

 研究了黄瓜子叶极性脂的组分及其脂肪酸组成于不同温度(25、20、15、10 ℃)处理下的变化。结果表明: 黄瓜子叶在15 ℃处理条件下虽无可见冷伤害症状, 但类脂成分已发生显著变化。双半乳糖甘油二酯(DGDG) 含量明显升高, 而磷脂酰胆碱(PC) 、磷脂酰乙醇胺(PE) 大幅度减少; 且主要类脂MGDG、DGDG及PC 中不饱和度高的分子种含量增多,最终导致总类脂的不饱和脂肪酸, 尤其是亚麻酸增多。说明黄瓜子叶在15 ℃下处理7 d , 已经对低温产生了冷适应性。     

笃斯越橘响应低温和短光周期的蛋白质组分析

以3年生笃斯越橘苗为材料,将苗木分别置于对照(23℃,日照长度14 h),低温短日照(4℃,日照长度10 h)和低温长日照(4℃,日照长度14 h)的人工气候室中。处理21 d后,采用同位素标记相对和绝对定量(iTRAQ)蛋白质组学技术测定枝条蛋白质表达变化情况。结果显示:通过质谱鉴定出5 972个蛋白质,600个差异表达蛋白,其中在低温短日照与对照比对组中,丰度显著上调蛋白有140个,丰度显著下调蛋白有114个;在低温长日照与对照比对组中,丰度显著上调蛋白有255个,丰度显著下调蛋白有122个;在低温短日照与低温长日照比对组中,丰度显著上调蛋白有39个,丰度显著下调蛋白有187个。这些蛋白主要参与(1)RNA代谢,(2)蛋白质翻译后修饰,(3)碳水化合物转运和代谢,(4)能量代谢和转换,(5)脂质代谢,(6)次生代谢产物合成,(7)抗氧化与胁迫防御,(8)光合作用,(9)无机离子转运和代谢。结果表明与抗冻性有关的蛋白差异表达主要受低温诱导,少数蛋白表达受低温和光周期共同影响,低温短光周期更有利于抗冻性形成。低温锻炼可显著提高RNA代谢、蛋白质翻译后修饰、抗氧化和防御反应、次生代谢产物合成以及脂质代谢过程中许多蛋白质的丰度,提示这些代谢途径和相关蛋白可能在笃斯越橘抗冻机制中起重要作用。     

莴苣花青素研究进展

花青素为水溶性类黄酮化合物，具有保护植物免受紫外伤害、清除活性氧组分、抵抗逆境以及改变植物色泽等多种生物学功能，同时具有抗衰老、防肥胖以及预防心血管疾病等保健功效。少数莴苣品种表型为紫色，富含花青素。本文论述了莴苣花青素的生物合成与调控途径，以及影响莴苣花青素积累的因素，旨在为开发富含花青素的莴苣功能性食品提供参考依据。     

Advances on role of extracellular vesicles in chronic liver diseases

In recent years, extracellular vesicles are found as an important medium for intercellular signal communication in prokaryotic and higher eukaryotic cells for regulating a variety of biological processes. Extracellular vesicles include exosomes, microvesicles and apoptotic bodies, and can be released into extracellular media by almost all types of cells in vivo and in vitro. Extracellular vesicles are released under physiological and pathological conditions, including liver diseases, and have a wide range of effects on the target cells. This review summarizes the progress in understanding the role of extracellular vesicles in chronic liver diseases. Specifically, how extracellular vesicles regulate non-alcoholic steatohepatitis, alcoholic liver disease, viral hepatitis, liver fibrosis and hepatocellular carcinoma is discussed in detail highlighting extracellular vesicles as a promising therapeutic target for chronic liver diseases.     

Repair effect of purple sweet potato anthocyanin on intestinal barrier injury in mice with ulcerative colitis induced by DSS

AIM To explore the repair effect of purple sweet potato anthocyanin on intestinal barrier injury of ulcerative colitis mice induced by dextrin sulfate sodium （DSS）. METHODS The mice were randomly divided into normal drinking group， DSS model group， different doses of purple sweet potato anthocyanin （12.5， 25， 50 and 75 mg/kg） groups， and 5-aminosalicylic acid （5-ASA） positive drug control group. Except using normal drinking water for control group， the mice in the other groups were treated with 2.5% DSS in drinking water for 7 days to induce the ulcerative colitis model. The mice in purple sweet potato anthocyanin treatment group and the 5-ASA positive drug control group were given the drug by intragastric gavage on the first day of modeling. The body weight of the mice and the hematocheziawere recorded every day. After continuous administration for 8 days， the mice in each group were killed and colon tissue was retained. Immunohistochemical technique （IHC） was used to detect the expression of tight junction protein ZO-1 and occludin and inflammatory factors tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the colon of mice. The expression of mucin in goblet cells of colon tissue was observed by glycogen PAS staining. The protein expression of ZO-1， occludin， TNF-α were determined by Western blot， Sirius red staining was used to detect colonic fibrosis in mice. RESULTS Compared with control group， the disease activity index and histological injury of DSS model mice were significantly increased（P<0.01）. Compared with model group， the disease activity index scores of the mice in different dose groups of purple sweet potato anthocyanin were decreased. The expression and distribution of ZO-1 and occludin in colon tissues were increased， and the expression and distribution of TNF-α and IL-6 in colon tissues were decreased. Glycogen PAS staining showed a significant increase in the distribution and expression of mucin in goblet cells of colon tissues in the purple sweet potato anthocyanin treatment group. Sirius red staining also showed that the degree of fibrosis in the purple sweet potato anthocyanin treatment groups was lower than that in model group. CONCLUSION Purple sweet potato anthocyanins has therapeutic effect on ulcerative colitis in mice induced by DSS， mainly through up-regulating the expression of tight junction proteins ZO-1 and occludin， to protect the integrity of intestinal barrier， inhibiting the expression of inflammatory cytokines TNF-α and IL-6 and intestinal fibrosis， to suppress the development of colonic inflammation.     

Progress on role of CCN1 in pulmonary diseases

Cysteine-rich angiogenic inducer 61 (Cyr61/CCN1) is an extracellular matrix-associated signaling protein consisting of 381 amino-acid residues, which has the regulatory function for a multitude of cellular responses. The pleiotropic effects of CCN1 on the initiation and resolution of inflammation as well as oncogenesis and development of tumor were reported. According to the numerous data from experimental and clinical studies, this article provides an overview on CCN1 and summarizes the latest understanding of the role of CCN1 in pulmonary diseases.     

葡萄着色期果皮蛋白质组分析

为了研究葡萄不同着色期果皮中蛋白质表达特征,以着色初期、中期和后期等3个着色时期的葡萄果皮为研究对象,运用2-DE、MALDI-TOF/TOF-MS质谱技术以及生物信息学方法对差异蛋白进行分析,结果表明:(1)双向凝胶电泳显示,果皮着色3个时期有1050个高度重复的蛋白点,差异显著的蛋白点有162个,其中108个蛋白得到鉴定,有87个蛋白映射到葡萄蛋白质组数据库中;3个时期均表达的差异蛋白有20个,且随着果皮颜色加深,差异蛋白数量呈上升趋势。(2)GO分析显示,ATP合成酶β亚基(ATPβ)极显著富集于磷酸核糖代谢过程,对着色初期果皮生理代谢的能量需求具有重要意义。(3)KEGG分析表明,碳代谢、生物固碳、磷酸戊糖、氨基酸生物合成等代谢通路在果皮着色的不同时期显著富集。(4)qRT-PCR分析显示,S–腺苷甲硫氨酸合成酶基因(VvMETK4)在果皮着色后期表达量最高。     

Effects of oxidative stress and inflammatory response on kidney injury in mice with hyperthyroidism

AIM To explore the effects of oxidative stress and inflammatory response on kidney injury induced by hyperthyroidism in mice. METHODS Forty male Kunming mice were randomly divided into control group （n=20） and L-thyroxine （T4） group （n=20）. The mice in T4 group were intraperitoneally injected with T4 diluent at a dose of 1 mg/kg to induce hyperthyroidism， and those in control group were injected with normal saline of the same volume. After 7 weeks， the mice were weighed and dissected， the kidneys were removed and weighed， and the length of tibia was also measured. The activity of superoxide dismutase （SOD） and the content of malondialdehyde （MDA） in the kidney tissues were detected. The pathological changes of the kidney tissues were observed by HE staining. The levels of 4-hydroxynonenal （4-HNE）-modified proteins， interleukin-1 receptor-associated kinase 1 （IRAK1） and tumor necrosis factor receptor-related factor 6 （TRAF6） were determined by Western blot and immunohistochemistry. RESULTS Compared with control group， the body weight of the mice was decreased， while the kidney size and weight were increased significantly in T4 group. In addition， the ratios of kidney weight/body weight and kidney weight/tibia length were also increased （P<0.05）. In T4 group， the renal tubules were enlarged， and the epithelial cells of renal tubules were swollen and exfoliated， with vacuolar degeneration. Furthermore， reduced SOD activity， and increased MDA content and 4-HNE-modified proteins were found in T4 group， all of which were related to oxidative stress （P<0.05）. The levels of inflammation-related proteins IRAK1 and TRAF6 were significantly increased in T4 group （P<0.05）. CONCLUSION Excessive T4 may lead to kidney hypertrophy and injury in mice， and the mechanism may be related to oxidative stress and inflammatory response.     

茄科植物WRKY转录因子的研究进展

WRKY蛋白是植物中最大的具有重要作用的转录因子家族之一,通过特异性结合启动子区域的W-Box来调控基因的表达,其成员参与了茄科(Solanaceae)植物的生长、发育、代谢、生物和非生物胁迫响应和激素信号的转导等进程。综述茄科植物WRKY转录因子表达模式和在生物和非生物胁迫中调控作用的研究进展。     

Regulatory role of CCN1 in lipopolysaccharide-induced mouse acute lung injury

AIM: To observe the cellular location and expression change of cysteine-rich protein 61 (CYR61/CCN1) in lung tissues of the mice with lipopolysaccharide (LPS) intratracheal instillation, and to clarify the regulatory role of CCN1 expression in mediating inflammatory response. METHODS: The expression change of CCN1 in the lung tissues in vivo was observed by the method of immunohistochemistry, and immunofluorescence was employed to certify the cellular location of CCN1 in bronchial epithelial cells. Bronchial epithelial 16HBE cells were cultured in vitro, and the expression of CCN1 under the condition of LPS stimulation was quantified by RT-qPCR and Western blot with or without specific inhi-bitors of ERK1/2, JNK, P38 and PI3K signaling pathways. The mRNA expression levels of interleukin-6 (IL-6), IL-8, transformrg growth factor-β (TGF-β) and vascular endothlial growth factor (VEGF) were measured by RT-qPCR under the condition of recombinant CCN1 exposure or transfection with CCN1-siRNA. RESULTS: The results of immunohistochemistry indicated that CCN1 was primarily located in bronchial epithelium. The results of immunofluorescence revealed that CCN1 was localized in the cytoplasm. The specific inhibitors of ERK1/2, JNK, P38 and PI3K signaling pathways reversed the up-regulation of CCN1 upon LPS stimulation. Exposure to recombinant CCN1 resulted in the up-regulation of IL-6, IL-8, TGF-β and VEGF, while LPS-related up-regulation of IL-6, IL-8, TGF-β and VEGF was blocked by silencing of CCN1. CONCLUSION: Airway epithelium-derived CCN1 is up-regulated under the condition of lung injury and the regulatory mechanism involves ERK1/2, JNK, P38 and PI3K signal transduction pathways. CCN1 acts as an inflammatory mediator in amplification of inflammatory response, laying theoretical basis for the potential molecular therapeutic target of acute lung injury.     

Effects of resveratrol on levels of ceramide via regulating miRNA-122 in treating non-alcoholic fatty liver disease

AIM: To observe the therapeutical effects of resveratrol on non-alcoholic fatty liver disease and its potential mechanism. METHODS: Male C57BL/6J mice were fed with high-fat and high-cholesterol diet to established non alcoholic fatty liver disease model, and were administrated with resveratrol at doses of 80 mg/kg and 160 mg/kg. After 4-week treatment, the blood sample was collected for determination of total cholesterol (TC) and triglyceride (TG). The liver tissues were harvested for measuring the liver lipid content. The histopathological examination were conducted with hematoxylin and eosin staining. The ceramide levels in the liver tissues were detected by HPLC-MS. The microRNA (mi-RNA)-122 levels in the liver tissues were detected by real-time PCR. The protein levels of serine palmitoyltransferase (SPT) were determined by Western blot. The HepG2 cells were cultured and divided into 5 groups:control group, model group (induced by 0.25 mmol/L oleic acid), model+resveratrol group (treated with 5 μmol/L resveratrol), miRNA-122 siRNA group and resveratrol+miRNA-122 siRNA group. Except control group, the cells in other groups were stimulated with oleic acid and incubated with respective drugs simultaneously for 24 h. The levels of TC, TG and ceramide in the cells of each group were measured. The protein levels of SPT in each group were determined by Western blot. RESULTS: In non-alcoholic fatty liver disease mice, resveratrol dose-dependently reduced the serum TC and TG levels, decreased the lipid deposition, the ceramide level and the SPT protein level, and increased the level of miRNA-122 in the liver tissues. In the in vitro study, compared with model group, resveratrol reduced the serum TC and TG levels, decreased the ceramide level, reduced the SPT protein level. Compared with control group, the levels of TC, TG and ceramide, and the protein expression of SPT were increased in miRNA-122 siRNA group. Compared with miRNA-122 siRNA group, no statistical difference of TC, TG, ceramide and protein expression of SPT in resveratrol combined miRNA-122 siRNA group was observed. CONCLUSION: Resveratrol significantly reduces lipid accumulation by reduction of miRNA-122 and ceramide levels, and decrease in SPT protein levels in the liver.     

Advance in study of batokines

Brown adipose tissue is a type of adipose tissue and is present in all mammals. It is not only the main site for adaptive thermogenesis in vivo, but also secretes and releases many cytokines in the form of endocrine to regulate a variety of metabolic processes and prevent and treat obesity and metabolic diseases. Therefore, identification of the types and effects of brown adipocytokines (batokines) may be crucial for the treatment of a variety of obesity-related metabolic diseases. Based on the latest research progress, batokines and their functions are reviewed.