Anti-VEGFR-2 Kinase Effects of Cyclo (Nα-dinicotinoyl)-bis-[(L-valinyl)- L-lysine] and its Anticancer Activities Against Different Cancer Cell Lines

The current work aimed at preparing a cyclo (Nα-dinicotinoyl)-bis-[(L-valinyl)-L-lysine] from previously established synthetic routs. The derivative was investigated for its potential anticancer activities as well as its possible mechanism of action. The prepared compound showed variable anticancer activities against all tested cell lines. Furthermore, it showed very promising activities in terms of obtained IC50 values compared to known used drugs. The mechanism of action studies showed that the prepared tripeptide may act on cancerous cells through its inhibitory action on tyrosine kinase pathway. Animal model experiments proved the potential of the synthesized tripeptide as an anticancer agent against PC3 cancer cells

Statistical Optimization Approaches for High Cell Biomass Production of Lactobacillus casei

216-221Probiotic bacteria are known to treat and prevent diseases and hence promote physical and mental wellness due to their significant brain-gut relationship. The main challenge involved in probiotic commercialization is the bio processing limitation to produce high cell mass, especially with the cultivation of lactic acid bacteria which produces lactic acid as a by product. Synthesis of lactic acid by lactic acid bacteria inhibits bacterial growth, and in turn disrupts high cell mass production. Current work presents the findings for Lactobacillus casei medium optimization by response surface methodology in shake flask level. A simple medium using 4 components: lactose, soybean meal, yeast extract and magnesium sulphate has been identified to produce high cell mass than generic mediaused for probiotic cultivation, such as the MRS medium. Secondly, response surface methodology using Box-Behken Design was employed as an optimization strategy. After optimization process, the production of Lactobacillus casei biomass increased by about 164.6% recording 6.51g.L-1 compared to cell biomass obtained using initial un-optimized medium (2.46g.L-1)

Medium Optimization using Response Surface Methodology for High Cell Mass Production of Lactobacillus acidophilus

608-614Lactobacillus acidophilus belongs to probiotic microflora inhabiting human gut that provide beneficially enhances human health. Besides balancing the intestinal flora and inhibiting pathogenic microorganisms, the existence of L. acidophilus inside the intestine can restore gut flora following antibiotics treatments. However, usually microorganisms from lactic acid bacteria group are known as fastidious microorganism and naturally required complex nutrients to promote their cellular growth. Therefore, twelve reported cultivation media were screened for their capability to support cell growth of L. acidophilus. The most suitable medium was further optimized using response surface methodology (RSM) and Box-Behnken design to maximize cell growth of L.acidophilus. Using this statistical approach, about 2.5-fold increase in maximal cell dry weight was achieved (5.14 g L-1) compared to the original medium (2.05 g L-1).This increase was accompanied by a significant increase in cell growth rates as well. The new medium formulation composed of (g L-1): glucose, 50; yeast extract, 20.91; ammonium citrate, 3.42; citric acid, 0.5; KH2PO4, 1.5; MgSO4.7H2O, 0.4; MnSO4.7H2O, 0.05; sodium acetate, 1; tween 80, 1

The effect of mycorrhizal fungi and organic fertilizers on quantitative and qualitative traits of two important satureja species

The quantitative yield and essential oil percentage and composition of two important savory species in response to various fertilizers were explored in a field experiment as a factorial study based on a randomized complete block design with three replications in north Lorestan, Iran, in 2017–2019. The first factor was assigned to three mycorrhizal fungi (Funneliformis mosseae, Rhizophagus irregularis, and Glomus fasciculatum), phosphate biofertilizer (Baravar-2), fish manure (800 kg/ha), cattle manure (20 t/ha), vermicompost (5 t/ha), and a control (no fertilization); the second factor was assigned to two savory species, including Satureja khuzestanica and S. rechingeri. The results of the combined analysis of variance for the second and third years showed that the simple effects of fertilizers and species were significant on all recorded traits, except for some constituents of the essential oil. Among the mycorrhizal fungi, R. irregularis and S. khuzestanica outperformed S. rechingeri in all traits, except for essential oil content and yield. The interaction between year and species was significant for all traits. The essential oil content of S. rechingeri in the third year (5.1%) was 18% higher than that of S. rechingeri in the second year (4.3%) and 41% higher than that of S. khuzestanica in the third year (3.6%). According to the results, the foliar application of vermin compost at a rate of 5 t/ha can contribute to the sustainable production of both savory species, improving their growth and essential oil yield

Tree bark scrape fungus: a potential source of laccase for application in bioremediation of non-textile dyes

Although laccase has been recognized as a wonder molecule and green enzyme, the use of low yielding fungal strains, poor production, purification, and low enzyme kinetics have hampered its large-scale application. Thus,this study aims to select high yielding fungal strains and optimize the production, purification, and kinetics of laccase of Aspergillus sp. HB-RZ4. The results obtained indicated that Aspergillus sp. HB-RZ4 produced a significantly large amount of laccase under meso-acidophilic shaking conditions in a medium containing glucose and yeast extract. A 25 μM CuSO4 was observed to enhance the enzyme yield. The enzyme was best purified on a Sephadex G-100 column. The purified enzyme resembled laccase of A. flavus. The kinetics of the purified enzyme revealed high substrate specificity and good velocity of reaction,using ABTS as a substrate. The enzyme was observed to be stable over various pH values and temperatures. The peptide structure of the purified enzyme was found to resemble laccase of A. kawachii IFO 4308. The fungus was observed to decolorize various dyes independent of the requirement of a laccase mediator system. Aspergillus sp. HB-RZ4 was observed to be a potent natural producer of laccase, and it decolorized the dyes even in the absence of a laccase mediator system. Thus, it can be used for bioremediation of effluent that contains non-textile dyes. © 2020 Sayyed et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Investigation of Growth Inhibitory Effects of cyclo (Nα-pyrido)-bis-[(L-valinyl)-L-ornthenyl acid hydrazide] on Various Cancer Cells as well as in vitro VEGFR-2 Kinase Inhibition

During the current work, we synthesized a new peptide derivative; 4,13-diisopropyl-2,5,12,15-tetraoxo-3,6,11,14-tetraaza-1(3,5)-pyridinacyclopentadecaphane-7-carbohydrazide. The prepared hydrazide was investigated for its in vivo as well as in vitro anticancer effects. Results revealed that this derivative has a great potential against 6 cancerous cell lines. Furthermore, the highest effect was obtained against HT1080 and HeLa cells, where the compound showed 7.4- and 15.1-folds increased activity against them, respectively. Additionally, the compound seems to exert its potential anticancer effect by affecting the kinase enzyme VEGFR-2. Finally, the compound showed promising results when tested in in vivo against prostate cancer developed animal models

Bioprocess optimization for pectinase production using Aspergillus niger in a submerged cultivation system

Background: Pectinase enzymes present a high priced category of microbial enzymes with many potential applications in various food and oil industries and an estimated market share of $ 41.4 billion by 2020. Results: The production medium was first optimized using a statistical optimization approach to increase pectinase production. A maximal enzyme concentration of 76.35 U/mL (a 2.8-fold increase compared with the initial medium) was produced in a medium composed of (g/L): pectin, 32.22; (NH4)2SO4, 4.33; K2HPO4, 1.36; MgSO4.5H2O, 0.05; KCl, 0.05; and FeSO4.5H2O, 0.10. The cultivations were then carried out in a 16-L stirred tank bioreactor in both batch and fed-batch modes to improve enzyme production, which is an important step for bioprocess industrialization. Controlling the pH at 5.5 during cultivation yielded a pectinase production of 109.63 U/mL, which was about 10% higher than the uncontrolled pH culture. Furthermore, fed-batch cultivation using sucrose as a feeding substrate with a rate of 2 g/L/h increased the enzyme production up to 450 U/mL after 126 h. Conclusions: Statistical medium optimization improved volumetric pectinase productivity by about 2.8 folds. Scaling-up the production process in 16-L semi-industrial stirred tank bioreactor under controlled pH further enhanced pectinase production by about 4-folds. Finally, bioreactor fed-batch cultivation using constant carbon source feeding increased maximal volumetric enzyme production by about 16.5-folds from the initial starting conditions

Statistically Designed Bioprocess for Enhanced Production of Alkaline Protease in Bacillus cereus HP_RZ17

491-498Alkaline protease is one of the bulk enzymes having wide commercial demand for various applications. It is commercially produced by a submerged fermentation process employing various bacteria, Bacillus sp. being the most widely used species. Statistical optimization of the process for the production of alkaline proteases from rhizospheric bacteria and its application in the biocontrol of plant pathogens has not been explored fully and needs to be studied for the development of efficient bioprocess. We report the enhanced production of alkaline protease in the minimal salt medium (MSM) optimized using statistical approaches such as Plackett Burman Design (PBD) and Response Surface Methodology (RSM). In the first step; PBD, among the total eight variables, three variables namely, yeast extract (pppBacillus cereus HP_RZ17. These three variables were further analyzed in the second step i.e. Central Composite Design (CCD) of RSM. The optimum yield of alkaline protease by B. cereus HP_RZ17 (130.72 UmL-1) was obtained under the optimal conditions such as yeast extract (0.899% w/v), fructose (0.873% w/v), and pH (11.25) of production media. The statistically optimized values of variables used for the scale-up of the process at 5 L capacity bioreactor enhanced the alkaline protease yield (132.48 UmL-1) by 1.09 fold vis-à-vis un-optimized protocol (121.96 UmL-1) in B. cereus HP_RZ17