作物秸秆对黄瓜衰老中根系活力和叶片氮代谢的影响

以‘津优4号’黄瓜为试验材料,研究施用不同作物秸秆对衰老过程中黄瓜根系活力和叶片氮代谢关键酶、叶片氮素含量及可溶性蛋白含量等影响。结果表明,与对照相比,作物秸秆还田不仅显著提高了黄瓜的根系活力、叶绿素含量和叶片氮代谢关键酶硝酸还原酶、谷氨酰胺合成酶、谷氨酸合成酶的活性,降低了谷氨酸脱氢酶活性,而且还降低了叶片铵态氮的含量(15.6 μg·g^-1),提高了叶片硝态氮、可溶性蛋白及游离氨基酸的含量,有效地保持较高的氮代谢水平,延缓了黄瓜的衰老。其中施用玉米秸秆效果最好,黄瓜的根系活力、硝酸还原酶活性、可溶性蛋白含量分别比对照提高了23.4%、33.3%、18.7%,其次为花生秸秆,硝酸还原酶活性比对照提高了10.8%,施用稻壳效果不明显。     

Pharmacokinetic aspects and in vitro–in vivo correlation potential for lipid-based formulations

Lipid-based formulations have been an attractive choice among novel drug delivery systems for enhancing the solubility and bioavailability of poorly soluble drugs due to their ability to keep the drug in solubilized state in the gastrointestinal tract. These formulations offer multiple advantages such as reduction in food effect and inter-individual variability, ease of preparation, and the possibility of manufacturing using common excipients available in the market. Despite these advantages, very few products are available in the present market, perhaps due to limited knowledge in the in vitro tests (for prediction of in vivo fate) and lack of understanding of the mechanisms behind pharmacokinetic and biopharmaceutical aspects of lipid formulations after oral administration. The current review aims to provide a detailed understanding of the in vivo processing steps involved after oral administration of lipid formulations, their pharmacokinetic aspects and in vitro in vivo correlation (IVIVC) perspectives. Various pharmacokinetic and biopharmaceutical aspects such as formulation dispersion and lipid digestion, bioavailability enhancement mechanisms, impact of excipients on efflux transporters, and lymphatic transport are discussed with examples. In addition, various IVIVC approaches towards predicting in vivo data from in vitro dispersion/precipitation, in vitro lipolysis and ex vivo permeation studies are also discussed in detail with help of case studies.KEY WORDS: Pharmacokinetics, Lipolysis, IVIVC, Efflux transporters, Lymphatic delivery, Food effectAbbreviations: ADME, absorption/distribution/metabolism/elimination; AUC, area under the curve; BCS, biopharmaceutics classification system; BDDCS, biopharmaceutics drug disposition classification system; CACO, human epithelial colorectal adenocarcinoma cells; C_max, maximum plasma concentration; CMC, critical micellar concentration; CYP, cytochrome; DDS, drug delivery systems; FaSSGF, fasted-state simulated gastric fluid; FaSSIF, fasted-state simulated intestinal fluid; FeSSIF, fed-state simulated intestinal fluid; GIT, gastrointestinal tract; IVIVC, in vitro in vivo correlation; LCT, long chain triglyceride; LFCS, lipid formulation classification system; log P, n-octanol/water partition coefficient; MCT, medium chain triglyceride; MDCK, Madin–Darby canine kidney cells; NCE, new chemical entity; P-app, apparent permeability; P-gp, permeability glycoprotein; SCT, short chain triglyceride; SEDDS, self-emulsifying drug delivery system; SIF, simulated intestinal fluid; SMEDDS, self-microemulsifying drug delivery system; SNEDDS, self-nanoemulsifying drug delivery system; Vit E, vitamin E     

BCG-induced trained immunity in macrophage: reprograming of glucose metabolism

Abstract

Memory is no longer a privilege of adaptive immunity. Innate immune cells can exhibit a long-term immune activation after infection or vaccination, which is called “trained immunity.” In addition to defense against mycobacterial infection, BCG-induced trained immunity can also exert nonspecific protection, which is regulated by metabolic rewiring and epigenetic reprograming. Enhanced glycolysis and glutamine-driven tricarboxylic acid cycle have been proven to be important metabolic pathways for trained immunity induced by BCG, which is dependent on Akt/mTOR pathway.     

Complement and human T cell metabolism: Location,location, location

The complement system represents one of the evolutionary oldest arms of our immune system and is commonly recognized as a liver-derived and serum-active system critical for providing protection against invading pathogens. Recent unexpected findings, however, have defined novel and rather “uncommon” locations and activities of complement. Specifically, the discovery of an intracellularly active complement system—the complosome—and its key role in the regulation of cell metabolic pathways that underly normal human T cell responses have taught us that there is still much to be discovered about this system. Here, we summarize the current knowledge about the emerging functions of the complosome in T cell metabolism. We further place complosome activities among the non-canonical roles of other intracellular innate danger sensing systems and argue that a “location-centric” view of complement evolution could logically justify its close connection with the regulation of basic cell physiology.     

Metabolic determinants of lupus pathogenesis

The metabolism of healthy murine and more recently human immune cells has been investigated with an increasing amount of details. These studies have revealed the challenges presented by immune cells to respond rapidly to a wide variety of triggers by adjusting the amount, type, and utilization of the nutrients they import. A concept has emerged that cellular metabolic programs regulate the size of the immune response and the plasticity of its effector functions. This has generated a lot of enthusiasm with the prediction that cellular metabolism could be manipulated to either enhance or limit an immune response. In support of this hypothesis, studies in animal models as well as human subjects have shown that the dysregulation of the immune system in autoimmune diseases is associated with a skewing of the immunometabolic programs. These studies have been mostly conducted on autoimmune CD4⁺ T cells, with the metabolism of other immune cells in autoimmune settings still being understudied. Here we discuss systemic metabolism as well as cellular immunometabolism as novel tools to decipher fundamental mechanisms of autoimmunity. We review the contribution of each major metabolic pathway to autoimmune diseases, with a focus on systemic lupus erythematosus (SLE), with the relevant translational opportunities, existing or predicted from results obtained with healthy immune cells. Finally, we review how targeting metabolic programs may present novel therapeutic venues.     

Interaction of pretilachlor with PS-II activity of the cyanobacterium Desmonostoc muscorum PUPCCC 405.10

Interaction of pretilachlor with photosystem (PS)-II of the cyanobacterium Desmonostoc muscorum PUPCCC 405.10 has been studied in this paper. Pretilachlor negatively affected growth, chlorophyll a (Chl a), photosynthesis, and carbon dissimilation in a dose-dependent manner. Effects were also observed in PSs, especially PS-II (an 11–35% decrease), as well as the whole photosynthetic electron transport activity. The fluorescence emission spectrum of Chl a revealed a dose-dependent effect of pretilachlor on both the antenna and the core complex of PSs, with more severe effect on the former. Data of O-J-I-P fluorescence transient of Chl a revealed that pretilachlor interfered with electron flow between Q_A and Q_B sites of PS-II. It was further observed that pretilachlor decreased maximum fluorescence, variable and relative variable fluorescence, maximum quantum yield, quantum yield of electron transport, the rate of trapped exciton movement, quantum yield of electron transfer, and performance index of primary photochemistry; however, there was a progressive increase in the net rate of PS-II closure, quantum yield of energy dissipation, and effective antenna size per active reaction center. A decrease in photosynthetic activity leads to a decrease in carbon dissimilation, as evidenced by low activity of glucose-6-phosphate dehydrogenase and pyruvate kinase. Thus, pretilachlor, which is otherwise known to kill weeds by interfering with cell division, affected the growth of the cyanobacteria by interacting with PS-II.     

Cellular metabolism dictates T cell effector function in health and disease

In a healthy person, metabolically quiescent T lymphocytes (T cells) circulate between lymph nodes and peripheral tissues in search of antigens. Upon infection, some T cells will encounter cognate antigens followed by proliferation and clonal expansion in a context-dependent manner, to become effector T cells. These events are accompanied by changes in cellular metabolism, known as metabolic reprogramming. The magnitude and variation of metabolic reprogramming are, in addition to antigens, dependent on factors such as nutrients and oxygen to ensure host survival during various diseases. Herein, we describe how metabolic programmes define T cell subset identity and effector functions. In addition, we will discuss how metabolic programs can be modulated and affect T cell activity in health and disease using cancer and autoimmunity as examples.     

共转录因子CITED1在小鼠骨代谢中的调控作用

目的在体研究CITED1在骨代谢即成骨/破骨平衡中的调节作用,为骨质疏松的治疗提供相应的理论基础。方法利用野生型小鼠(WT小鼠)和构建的CITED1基因敲除小鼠(KO小鼠),显微电子计算机断层扫描(CT)定量测量WT小鼠和KO小鼠股骨长度、骨量和骨皮质以及骨松质厚度等骨骼表型。用ELISA检测骨代谢的血液学相关指标。用RT-qPCR检测骨标志基因的表达,从分子水平探究骨代谢改变的原因。结果 KO小鼠颅骨成骨细胞中CITED1表达极少,表明敲除成功。KO小鼠股骨长度、骨量和骨皮质以及骨松质厚度显著高于WT小鼠。KO小鼠外周血血清中I型原胶原肽(P1NP)、骨钙素(OC)和骨碱性磷酸酶(BALP)浓度均显著高于WT小鼠,而抗酒石酸酸性磷酸酶(TRAP)的浓度显著低于WT小鼠。RT-qPCR结果显示,KO小鼠颅骨成骨细胞中OC和BALP基因表达较WT小鼠显著增加(P<0. 001);同时,KO小鼠颅骨成骨细胞中抗酒石酸酸性磷酸酶(TRAP)的表达较WT小鼠显著降低(P<0. 05)。结论小鼠CITED1敲除后可以通过上调OC和BALP基因表达,下调TRAP基因的表达,促进骨形成,抑制骨吸收。