Inhibition of yeast‐to‐filamentous growth transitions in Candida albicans by a small molecule inducer of mammalian apoptosis

The opportunistic fungal pathogen of humans Candida albicans is able to grow in different morphological forms such as round or oval yeasts and filamentous hyphae and pseudohyphae. Morphogenesis, the ability to switch between the yeast and filamentous growth forms, is important for adapting to new microenvironments in the human host and for pathogenesis. The molecular pathways governing morphogenesis are complex and incompletely understood. Previously, we identified several small organic molecules that specifically inhibit the initiation of hyphal growth in C. albicans without affecting cell viability or budded growth. One molecule from that screen is known to induce apoptosis in mammalian cells. In this study, we have screened additional inducers of mammalian apoptosis and identified BH3I‐1, as well as several structural derivatives of BH3I‐1, that act as specific inhibitors of morphogenesis under a variety of environmental conditions. Chemical epistasis experiments suggest that BH3I‐1 acts downstream of the hypha‐specific gene regulators Rfg1, Nrg1 and Ume6.     

Protection efficiencies of surface-active inhibitors in zinc-air batteries

Zinc (Zn) particles in alkaline electrolyte of a Zn-air battery (ZAB) are unstable and prone to corrosion. Zinc oxide (ZnO) generated on the surface of Zn particles affects the electrochemical reactions and reduces the battery efficiency. Thus, inhibiting the self-corrosion rate of Zn particles has become acritical issue for the development of these batteries. In this study, a research endeavor has been attempted by employing three types and concentrations of organic inhibitors in ZABs to constrain Zn anode corrosion. Significant analyses like polarization curve, constant current discharge, AC impedance, and dendrite growth are executed for in-depth understanding of the influences of these inhibitors. The experimental results reveal that the inhibiting efficiency of 10 wt% Sodium dodecyl benzene sulfonate surpassed polyethylene glycol 600 (PEG 600) and polysorbate 20 (Tween 20), with a maximum current density of 476.20 mA/cm² and voltage output of 1.4 V along with discharge capacitance of 10.31 Ah for 2 hours and 8 minutes. Zn anode surface analysis exposes significant dendrite growth and elemental Zn required for passivation suppression. Nevertheless, the results are also justified by Nyquist and Bode plots. Thus, the selected inhibitor will proficiently guarantee the enhanced performance and stability of the ZABs obtained and provide enormous opportunities for its applications.     

Small-Molecule Inhibition of Glucose Transporters GLUT-1–4

Glucose addiction is observed in cancer and other diseases that are associated with hyperproliferation. The development of compounds that restrict glucose supply and decrease glycolysis has great potential for the development of new therapeutic approaches. Addressing facilitative glucose transporters (GLUTs), which are often upregulated in glucose-dependent cells, is therefore of particular interest. This article reviews a selection of potent, isoform-selective GLUT inhibitors and their biological characterization. Potential therapeutic applications of GLUT inhibitors in oncology and other diseases that are linked to glucose addiction are discussed.     

Nitroreductase-Mediated Release of Inhibitors of Lysine-Specific Demethylase 1 (LSD1) from Prodrugs in Transfected Acute Myeloid Leukaemia Cells

Lysine-specific demethylase 1 (LSD1) has evolved as a promising therapeutic target for cancer treatment, especially in acute myeloid leukaemia (AML). To approach the challenge of site-specific LSD1 inhibition, we developed an enzyme-prodrug system with the bacterial nitroreductase NfsB (NTR) that was expressed in the virally transfected AML cell line THP1-NTR⁺. The cellular activity of the NTR was proven with a new luminescent NTR probe. We synthesised a diverse set of nitroaromatic prodrugs that by design do not affect LSD1 and are reduced by the NTR to release an active LSD1 inhibitor. The emerging side products were differentially analysed using negative controls, thereby revealing cytotoxic effects. The 2-nitroimidazolyl prodrug of a potent LSD1 inhibitor emerged as one of the best prodrug candidates with a pronounced selectivity window between wild-type and transfected THP1 cells. Our prodrugs are selectively activated and release the LSD1 inhibitor locally, proving their suitability for future targeting approaches.     

Nutrient contents,rumen protein degradability and antinutritional factors in some colour- and white-flowering cultivars of Vicia faba beans

Six colour-flowering (Scirocco, Alfred, Carola, Condor, Tina and Herz Freya) and six white-flowering (Caspar, Albatros, Gloria, Tyrol, Vasco and Cresta) cultivars of Vicia faba were studied. The crude protein contents of colour- and white-flowering cultivars were 267±13·6 and 283±18·8 g kg⁻¹, respectively, which did not differ significantly at P<0·05. The levels of lipids, crude fibre, starch and ash varied from 14 to 22 g kg⁻¹, 88 to 143 g kg⁻¹, 407 to 485 g kg⁻¹ and 32 to 42 g kg⁻¹, respectively. The calculated organic matter digestibility (OMD) and metabolisable energy (ME) of the white-flowering cultivars were significantly higher (P<0·001) than those of the colour-flowering cultivars (OMD: 889·1±26·6 g kg⁻¹ vs 797·5±17·1 g kg⁻¹; ME: 13·97±0·49 vs 12·30±0·34 MJ kg⁻¹). In all cultivars, sulphur amino acids were lower than adequate concentration when compared with recommended amino acid pattern of FAO/WHO/UNO reference protein for a 2–5-year-old child. The in vitro rumen nitrogen degradability of colour-flowering cultivars was significantly lower (P<0·01) compared to that of white-flowering cultivars (71·4±9·3% vs 88·0±11·1%). Amongst colour-flowering varieties, the contents of total phenols (TP), tannins (T) and condensed tannins (CT) were highest in Alfred (28·3, 21·0 and 35·4 g kg⁻¹, respectively). The contents of TP and T were similar (about 15 and 10 g kg⁻¹, respectively) in Carola, Tina and Herz Freya, and the CT were in the order: Condor>Herz Freya>Carola. The CT were not detected in white-flowering varieties, T were virtually absent and TP were extremely low (4·0–4·9 g kg⁻¹). The activities of other antinutritional factors (white- and colour-flowering cultivars, respectively: trypsin inhibitor activity 3·05±0·34 and 1·85±0·09 mg trypsin inhibited g⁻¹; lectin 27·2±9·4 and 27·1±5·1 mg ml⁻¹ assay medium producing haemagglutination; phytate 15·0±2·7 and 16·6±2·3 g kg⁻¹) were very low. A strong negative correlation (r=-0·92, P<0·001) between tannins and in vitro rumen protein degradability was observed which suggested that tannins have adverse effect on protein degradability. Similarly negative correlations between tannin levels and metabolisable energy (r=-0·89; P<0·001) and organic matter digestibility (r=-0·89; P<0·001) were observed. The correlation coefficient between trypsin inhibitor activity and tannins was negative and highly significant (r=-0·88, P<0·001), whereas between tannins and saponins it was significantly positive (r=0·96, P<0·001). ©1997 SCI     

碱性蛋白酶水解制备蛋黄降压肽工艺条件优化

以经超临界CO2萃取除去大部分蛋黄油和卵磷脂的鸡蛋蛋黄蛋白质为原料,选用碱性蛋白酶水解该蛋白质制备蛋黄降压肽(ACEI),用高效液相色谱(HPLC)测定酶解产物对血管紧张素酶(ACE)的抑制活性(IP)。研究了不同水解温度、酶用量([E]/[S])、底物浓度([S])和pH值时蛋白质水解度(DH)随时间的变化规律,并进一步考察了不同DH产物的氮溶解指数(NSI)及对ACE抑制活性(IP)。结果表明,获得具有较高活性和较好溶解性的产物需控制蛋白质DH在16%～20%之间,以IP为考察指标得到该碱性蛋白酶水解鸡蛋蛋黄蛋白质制备降压肽的适宜条件为:水解时间300min,水解温度45℃,[E]/[S]为50AU/kg,[S]为7%,pH值9.5,此时DH为16.3%,NSI值为89.09%,水解物对ACE的IP值可达到68.28%。     

电厂水处理药剂实验室评价及应用

通过控制循环冷却水动态模拟试验条件，研究阻垢缓蚀剂的性能，确定循环水应用的最佳控制指标。应用结果表明，试验研究所获取的运行参数对企业减少新鲜水用量、节约用水，保证电厂安全经济运行和可持续性发展具有指导意义。     

The Inhibition of the Inducible Nitric Oxide Synthase Enhances the DPSC Mineralization under LPS-Induced Inflammation

Nitric oxide (NO) is a key messenger in physiological and pathological processes in mammals. An excessive NO production is associated with pathological conditions underlying the inflammation response as a trigger. Among others, dental pulp inflammation results from the invasion of dentin by pathogenic bacteria. Vital functions of pulp mesenchymal stem cells (DPSCs, dental pulp stem cells), such as mineralization, might be affected by the inducible NOS (iNOS) upregulation. In this context, the iNOS selective inhibition can be considered an innovative therapeutic strategy to counteract inflammation and to promote the regeneration of the dentin-pulp complex. The present work aims at evaluating two acetamidines structurally related to the selective iNOS inhibitor 1400W, namely CM544 and FAB1020, in a model of LPS-stimulated primary DPSCs. Our data reveal that CM544 and even more FAB1020 are promising anti-inflammatory compounds, decreasing IL-6 secretion by enhancing CD73 expression-levels, a protein involved in innate immunity processes and thus confirming an immunomodulatory role of DPSCs. In parallel, cell mineralization potential is retained in the presence of compounds as well as VEGF secretion, and thus their angiogenetic potential. Data presented lay the ground for further investigation on the anti-inflammatory potential of acetamidines selectively targeting iNOS in a clinical context.     

Effects of three phenolic acids on chlorophyll content and growth of soybean and grain sorghum seedlings

Experiments were designed to test the hypothesis that interference with chlorophyll metabolism may be one mechanism of inhibition of plant growth in allelopathic interactions. Effects of ferulic,p-coumaric, and vanillic acids on soybean and grain sorghum growth and chlorophyll content were quantified and compared after seedlings were treated with these compounds in a nutrient culture. Following a 6-day treatment cycle, dry weights of soybean seedlings were reduced by both 10^–3 M and 5 × 10^–4 M treatments of ferulic,p-coumaric and vanillic acids. Soybean weight reductions in each case were paralleled by a significant reduction in the concentration (g Chl/mg dry wt) of chlorophylls a and b and total chlorophyll in the unifoliate leaves. Sorghum seedling growth was also reduced by each of the compounds at the 5 × 10^–4 M level, but leaf chlorophyll concentration was not below that of control plants.