Diacylglycerol: Efficacy and Mechanism of Action of an Anti‐Obesity Agent

Obesity is at the forefront of global health issues and directly contributes to many chronic illnesses. Several dietary components show promise in the treatment of obesity, one of which is oil rich in diacylglycerols (DAGs). Present objectives are to examine scientific knowledge concerning DAG to assess evidence supporting the effects on substrate oxidation rates, body weight and fat mass, and blood lipids, and to assess safety, as well as elucidate potential mechanisms of action. DAG can be synthesized by an enzymatic process to produce mainly 1, 3‐isoform DAG. This 1, 3‐DAG oil is believed to have the ability to increase β‐oxidation, to enhance body weight loss, to suppress body fat accumulation, and to lower serum triacylglycerol levels postprandially. While certain animal and human studies indicate that consumption of 1, 3‐DAG has positive physiological effects, others report no effect. The mechanisms of action of DAG are suggested to decrease the resynthesis of chylomicrons as well as shunting them directly to the liver through the portal vein, where they are oxidized. This increased fat oxidation may influence control of food intake by increasing satiety. Further study into the precise mechanism is required to understand its effects. Safety studies show no risks in consuming a diet rich in DAG oil. Overall, consumption of oils with higher amounts of DAG, specifically 1, 3‐DAG, may be useful in the battle against obesity.     

The Efficacy of Nano Silver Sulfadiazine and Nano Benzalkonium Chloride on Heterotrophic Biofilms

Microbiology - Silver sulfadiazine and benzalkonium chloride are biocidal agents known to be effective against microorganisms. Although planktonic cells are easily affected by these agents,...     

植物生长素的作用机制

介绍了生长素受体、生长素诱导基因以及生长素诱导ATPase活化,特别对近几年来生长素信号转导的研究进展进行了概述.     

Cancer: Towards a general theory of the target

General theories (GT) are reductionist explications of apparently independent facts. Here, in reviewing the literature, I develop a GT to simplify the cluttered landscape of cancer therapy targets by revealing they cluster parsimoniously according to only a few underlying principles. The first principle is that targets can be only exploited by either or both of two fundamentally different approaches: causality‐inhibition, and ‘acausal’ recognition of some marker or signature. Nonetheless, each approach must achieve both of two separate goals, efficacy (reduction in cancer burden) and selectivity (sparing of normal cells); if the mechanisms are known, this provides a definition of rational treatment. The second principle is target fragmentation, whereby the target may perform up to three categoric functions (cytoreduction, modulation, cytoprotection), potentially mediated by physically different target molecules, even on different cell types, or circulating freely. This GT remains incomplete until the minimal requirements for cure, or alternatively, proof that cure is impossible, become predictable.     

Oral Efficacy of Apigenin against Cutaneous Leishmaniasis: Involvement of Reactive Oxygen Species and Autophagy as a Mechanism of Action

Background

The treatment for leishmaniasis is currently based on pentavalent antimonials and amphotericin B; however, these drugs result in numerous adverse side effects. The lack of affordable therapy has necessitated the urgent development of new drugs that are efficacious, safe, and more accessible to patients. Natural products are a major source for the discovery of new and selective molecules for neglected diseases. In this paper, we evaluated the effect of apigenin on Leishmania amazonensis in vitro and in vivo and described the mechanism of action against intracellular amastigotes of L. amazonensis.

Methodology/Principal Finding

Apigenin reduced the infection index in a dose-dependent manner, with IC₅₀ values of 4.3 μM and a selectivity index of 18.2. Apigenin induced ROS production in the L. amazonensis-infected macrophage, and the effects were reversed by NAC and GSH. Additionally, apigenin induced an increase in the number of macrophages autophagosomes after the infection, surrounding the parasitophorous vacuole, suggestive of the involvement of host autophagy probably due to ROS generation induced by apigenin. Furthermore, apigenin treatment was also effective in vivo, demonstrating oral bioavailability and reduced parasitic loads without altering serological toxicity markers.

Conclusions/Significance

In conclusion, our study suggests that apigenin exhibits leishmanicidal effects against L. amazonensis-infected macrophages. ROS production, as part of the mechanism of action, could occur through the increase in host autophagy and thereby promoting parasite death. Furthermore, our data suggest that apigenin is effective in the treatment of L. amazonensis-infected BALB/c mice by oral administration, without altering serological toxicity markers. The selective in vitro activity of apigenin, together with excellent theoretical predictions of oral availability, clear decreases in parasite load and lesion size, and no observed compromises to the overall health of the infected mice encourage us to supports further studies of apigenin as a candidate for the chemotherapeutic treatment of leishmaniasis.     

Mechanism of Action of Two Flavone Isomers Targeting Cancer Cells with Varying Cell Differentiation Status

Apoptosis can be triggered in two different ways, through the intrinsic or the extrinsic pathway. The intrinsic pathway is mediated by the mitochondria via the release of cytochrome C while the extrinsic pathway is prompted by death receptor signals and bypasses the mitochondria. These two pathways are closely related to cell proliferation and survival signaling cascades, which thereby constitute possible targets for cancer therapy. In previous studies we introduced two plant derived isomeric flavonoids, flavone A and flavone B which induce apoptosis in highly tumorigenic cancer cells of the breast, colon, pancreas, and the prostate. Flavone A displayed potent cytotoxic activity against more differentiated carcinomas of the colon (CaCo-2) and the pancreas (Panc28), whereas flavone B cytotoxic action is observed on poorly differentiated carcinomas of the colon (HCT 116) and pancreas (MIA PaCa). Apoptosis is induced by flavone A in better differentiated colon cancer CaCo-2 and pancreatic cancer Panc 28 cells via the intrinsic pathway by the inhibition of the activated forms of extracellular signal-regulated kinase (ERK) and pS6, and subsequent loss of phosphorylation of Bcl-2 associated death promoter (BAD) protein, while apoptosis is triggered by flavone B in poorly differentiated colon cancer HCT 116 and MIA PaCa pancreatic cancer cells through the extrinsic pathway with the concomitant upregulation of the phosphorylated forms of ERK and c-JUN at serine 73. These changes in protein levels ultimately lead to activation of apoptosis, without the involvement of AKT.     

The Toxic Action of Molybdenum in Relation to Soils and Crops

The harmful effect of molybdenum on animals is well established, but there is comparatively little knowledge of the conditions in which molybdenum is poisonous to plants. Obvious differences in response to molybdenum poisoning in different soils have been previously noted, but no adequate explanation has been put forward.
Tomatoes grown in ordinary loam showed little outward sign of poisoning with heavy doses of sodium molybdate, but some depression of crop occasionally occurred, especially when the dose was divided into early and late treatments. The response varied with season and variety. On certain light and fen soils the plants were killed at an early stage with the heavier dressing of molybdate, and seriously injured with the lighter dose, the leaves showing the golden colour characteristic of molybdenum poisoning in various plants.
The reaction of different crops varied considerably in the same soil with similar treatments. On old cucumber soil tomatoes showed no sign of toxicity even with the heavy dressing, flax was progressively damaged with increasing doses, while Solanum nodiflorum was most seriously affected even with the lighter dressing of molybdate. It was impossible to predict the reaction between soil, poison and crop without actual experiment.
The growth of flax was greatly impeded on a manganese-deficient fen soil, and the molybdenum toxicity was masked in consequence. When the deficiency was corrected the poisonous effect of molybdenum on this soil was very marked, even with the lower dressing.
The composting of loam with peat usually, but not invariably, resulted in a reduction of the toxicity of molybdenum. The different results obtained with several crops on a variety of soils still yield no definite clue to the factors which determine the relative toxicity of molybdenum to plant growth and such points as soil acidity, response to climatic conditions and nutritive deficiencies are among those which need further investigation.     

Mechanism of Action of Showdomycin

Showdomycin, 2-β-d-ribofuranosylmaleimide, inhibited the incorporation of amino acids and purine and pyrimidine bases into macromolecules in E. coli K-12 cells at low concentrations. The inhibitory action of showdomycin could be reversed by the addition of a nucleoside or a sulfhydryl compound. In marked contrast to common nucleosides, the pseudouridine showed no such effect. This may indicate that the N-glycosyl linkage in the nucleoside is a structural requirement for its reversing activity on the inhibitory action of showdomycin.

N-Ethylmaleimide, which has structural similarity to showdomycin, inhibited the incorporation of amino acids and purine and pyrimidine bases as well as showdomycin. The inhibitory action of N-ethylmaleimide, however, was not reversed by the addition of a nucleoside. This may indicate that there may be difference in the mechanism of the inhibitory action between N-ethylmaleimide and showdomycin.     

Mechanism of Action of Showdomycin

The effect of showdomycin on the syntheses of deoxyribonucleotides from various pyrimidine and purine derivatives was studied in cell-free systems from E. coli.

The formations of deoxycytidine phosphates, deoxyuridine phosphates, deoxyguanosine phosphates and deoxyadenosine phosphates from the corresponding ribonucleoside diphosphates were all inhibited by low concentrations of showdomycin. The formation of deoxythymidine phosphates from dUMP was also very susceptible to the antibiotic. These inhibitory actions of showdomycin could be reversed by a sulfhydryl compound (mercaptoethanol) but not by nucleosides, in contrast to a previous finding that the inhibitory action of this antibiotic on the cell growth was reversed by compounds belonging to both of these groups.

N-Ethylmaleimide (NEM), a thiol reagent which has a structure related to the aglycone moiety of showdomycin, was also found to be a potent inhibitor of both the reduction of CDP and the methylation of dUMP as showdomycin. A mercurial thiol reagent, p-chloromercuribenzoic acid (PCMB), however, was found to be inactive against the methylation of dUMP although the salvage synthesis of dUMP was inhibited by low concentrations of this reagent.

The formations of deoxythymidine phosphates and of deoxyuridine phosphates from their respective pyrimidine bases and a deoxyribosyl donor were quite resistant to showdomycin.     

Mechanism of Action of Showdomycin

¹⁴C-Labelled showdomycin was rapidly taken up by Escherichia coli K-12 cells. The showdomycin uptake was highly temperature dependent, sensitive to azide and N-ethyl-maleimide, but was only partially inhibited by treatment with high concentration of iodoacetic acid.

The uptake of showdomycin was inhibited by a wide variety of nucleosides but not by purine and pyrimidine bases, nucleotides, ribose or ribose-5-phosphate. The inhibition of showdomycin uptake by adenosine was of a competitive type.

Since nucleosides inhibited the uptake of showdomycin but did not facilitate its efflux, they must play a role of inhibitors to the entry of the antibiotic into cells.

Removal of extracellular showdomycin by washing, or inhibition of its subsequent entry into cells by the addition of nucleosides or sulfhydryl compounds resulted in a rapid decrease in the intracellular level of the antibiotic during subsequent incubation.     

Mechanism of Action of Showdomycin

Among the syntheses of DNA, RNA and protein in Escherichia coli cells, the DNA synthesis was found to be preferentially inhibited at lower concentrations of showdomycin. At such lower concentrations of this antibiotic, serious decreases in the synthesis of deoxycytidine phosphates and in de novo synthesis of deoxythymidine phosphates were found in parallel with the decrease in the synthesis of DNA, although the syntheses of other pyrimidine nucleotides were not significantly diminished. The salvage synthesis of deoxythymidine phosphates was very resistant to this antibiotic. The inhibitory action of this antibiotic on DNA synthesis could be reversed by the concomitant addition of a thiol compound or a nucleoside. When a nucleoside was added after the completion of the inhibition by showdomycin, the recovery of the DNA synthesis from the inhibition was detected only after the recovery of the syntheses of pyrimidine ribotides, pyrimidine deoxyribotides and RNA have become distinct.     

胰岛素原C肽作用机制

Ｃ肽是胰岛素原中连接ＡＢ两条链的连接肽。在胰岛 β细胞分泌颗粒中 ,胰岛素原经蛋白酶裂解 ,形成等摩尔由ＡＢ链组成的胰岛素和Ｃ肽 ,然后分泌并进入血液。Ｃ肽的种族差异很大 ,其中人Ｃ肽含 31个氨基酸。在胰岛素原分子中Ｃ肽对胰岛素原分子的折叠、二硫键的正确配对等分子结构的形成起重要作用 ,而血液中游离Ｃ肽的生理功能却一直不清楚。近来的研究发现 ,给予Ｉ型糖尿病大鼠超生理剂量的人Ｃ肽配伍胰岛素治疗 ,能防止血管、神经机能障碍[1] ,长期 (3个月 )给予胰岛素配伍Ｃ肽 ,可使Ｉ型糖尿病病人减少尿白蛋白排泄率 ,改善肾功能和自主…     

Nano Defensin: A Promising Antibacterial Agent Against Colorectal Cancer Related Bacteria

International Journal of Peptide Research and Therapeutics - Colorectal cancer (CRC) is one of the most common causes of cancer death in the world. Although genes are considered the most important...     

Mechanism of Action of Luteinizing Hormone

WE have reported¹ studies on luteinized rat ovary in which we found that an approximate doubling of the rate of steroid synthesis following stimulation with luteinizing hormone was not associated with any change in the tissue NADPH/NADP⁺ concentration ratio. We concluded that it was unlikely that luteinizing hormone brought about the increase in steroid synthesis solely by increasing the production of NADPH by glucose 6-phosphate dehydrogenase or another cytoplasmic NADPH-linked dehydrogenase, as had been suggested^2,3.     

Mechanism of Action of Abscission Accelerators

Abscission zone explants of Gossypium hirsutum L., Cassia fistula L., and Coleus blumei Benth. were used to investigate correlations between endogenous rates of ethylene evolution and time of abscission. Additions of 0.1 nl/ml ethylene to the explants markedly accelerated abscission; continuous aeration of the explants, to prevent accumulation of small amounts of endogenously produced ethylene, inhibited abscission compared with that of sealed controls. Substances that stimulated abscission simultaneously accelerated ethylene evolution on all three species and at any position of application. The positional effects of auxin are explained as being due to differences in transport in the explant. Thus, distally applied auxin inhibits abscission, regardless of the accelerated rate of ethylene evolution, by being rapidly transported to the abscission zone. Auxin applied proximally stimulates abscission because it is unable to move as rapidly to the abscission zone and the ethylene effect becomes dominant. Ethylene was found to be most effective on aged tissues, and it is concluded that abscission rates are determined by an increase in sensitivity of the tissue to the ethylene that is already being produced.     

青蒿素类药物的作用机制:一个长久未决的基础研究挑战

青蒿素是中国自主研制的抗疟良药,高效、低毒,许多基于青蒿素研发的衍生物具有良好的抗疟效果,近年来已成为抗疟的一线药物,受到世界医疗卫生界的充分肯定.虽然青蒿素结构奇特,抑疟效果显著,但40年来其生物作用机制之谜一直未被彻底破解.针对青蒿素类药物的作用机制,提出了不同的假说,如血红素参与青蒿素的激活并被烷基化从而起到抑疟作用,线粒体参与青蒿素的激活和作用过程,某些特定的蛋白是青蒿素作用靶点等.除抑疟外,青蒿素类药物在杀灭其他种类寄生虫、抑制某些癌症细胞以及抗病毒、治疗类风湿等方面也有一定作用.本文将对青蒿素类药物作用机制的研究进行综述及展望,包括抗疟疾过程中的药物激活、作用靶点以及简要的青蒿素抑制肿瘤细胞作用机制,以期为今后的研究提供帮助.     

The Effect of Molybdenum upon the Nitrogen Metabolism of Anabaena cylindrica: II. A More Detailed Study of the Action of Molybdenum in Nitrate Assimilation

Molybdenum-deficiency in Anabaena cylindrica results in a decreaseof all the organic nitrogen fractions determined analyticallywith the exception of amide which occurs at approximately thesame concentration irrespective of the molybdenum status. Molybdenum-rich,nitrogen-starved cells assimilate nitrate to protein rapidlyin the dark; similarly treated molybdenum-deficient cells rapidlyreduce nitrate to ammonia and amide, but the further synthesisto peptides and proteins proceeds very slowly. The rate of endogenousrespiration is higher in deficient than in normal cells, butthe rate of glycolysis is lower. No period of adaptation isrequired, after the addition of molybdenum to deficient cells,before normal nitrogen metabolism commences. Glucose, acetate,fumarate, succinate, and citrate are respired by normal anddeficient cells in the dark. Acetate has no effect on nitratereduction, glucose stimulates the reduction for a short period,while fumarate (and probably succinate) and, somewhat less efficiently,citrate, stimulate reduction in both normal and deficient cellsand enable the deficient cells to assimilate nitrate completelyto protein. It would seem that, in the absence of molybdenum,there is an insufficient supply of hydrogen and/or energy donorsto permit complete nitrate assimilation.