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181.
Khan KM Rahim F Halim SA Taha M Khan M Perveen S Zaheer-Ul-Haq Mesaik MA Iqbal Choudhary M 《Bioorganic & medicinal chemistry》2011,19(14):4286-4294
Benzothiazole derivatives 1-26 have been synthesized and their in vitro β-glucuronidase potential has been evaluated. Compounds 4 (IC(50)=8.9 ± 0.25 μM), 5 (IC(50)=36.1 ± 1.80 μM), 8 (IC(50)=8.9 ± 0.38 μM), 13 (IC(50)=19.4 ± 1.00 μM), 16 (IC(50)=4.23 ± 0.054 μM), and 18 (IC(50)=2.26 ± 0.06 μM) showed β-glucuronidase activity potent than the standard (d-saccharic acid 1,4-lactone, IC(50)=48.4 ± 1.25 μM). Compound 9 (IC(50)=94.0 ± 4.16 μM) is found to be the least active among the series. All active analogs were also evaluated for cytotoxicity and none of the compounds showed any cytotoxic effect. Furthermore, molecular docking studies were performed using the gold 3.0 program to investigate the binding mode of benzothiazole derivatives. This study identifies a novel class of β-glucuronidase inhibitors. 相似文献
182.
Glycogen phosphorylase (GP) is a valid anti-diabetic target. Accordingly, we applied a drug discovery workflow to unveil novel inhibitory GP leads via combining pharmacophore modeling, QSAR analysis and in silico screening, followed by synthetic exploration of active hits. Virtual screening identified six low micromolar inhibitory leads from the National Cancer Institute (NCI) list of compounds. The most potent hits exhibited anti-GP IC(50) values of 3.2 and 4.1 μM. Synthetic exploration of hit 59 (IC(50)=4.1 μM) yielded 25 lead inhibitors with the best illustrating IC(50) of 3.0 μM. Interestingly, we prepared several novel mixed oxalyl amide anti-GP leads employing new chemical reaction involving succinic acid-based adducts. 相似文献
183.
184.
Elshahed MS Youssef NH Luo Q Najar FZ Roe BA Sisk TM Bühring SI Hinrichs KU Krumholz LR 《Applied and environmental microbiology》2007,73(15):4707-4716
We investigated the phylogenetic diversity and metabolic capabilities of members of the phylum Planctomycetes in the anaerobic, sulfide-saturated sediments of a mesophilic spring (Zodletone Spring) in southwestern Oklahoma. Culture-independent analyses of 16S rRNA gene sequences generated using Planctomycetes-biased primer pairs suggested that an extremely diverse community of Planctomycetes is present at the spring. Although sequences that are phylogenetically affiliated with cultured heterotrophic Planctomycetes were identified, the majority of the sequences belonged to several globally distributed, as-yet-uncultured Planctomycetes lineages. Using complex organic media (aqueous extracts of the spring sediments and rumen fluid), we isolated two novel strains that belonged to the Pirellula-Rhodopirellula-Blastopirellula clade within the Planctomycetes. The two strains had identical 16S rRNA gene sequences, and their closest relatives were isolates from Kiel Fjord (Germany), Keauhou Beach (HI), a marine aquarium, and tissues of marine organisms (Aplysina sp. sponges and postlarvae of the giant tiger prawn Penaeus monodon). The closest recognized cultured relative of strain Zi62 was Blastopirellula marina (93.9% sequence similarity). Detailed characterization of strain Zi62 revealed its ability to reduce elemental sulfur to sulfide under anaerobic conditions, as well as its ability to produce acids from sugars; both characteristics may potentially allow strain Zi62 to survive and grow in the anaerobic, sulfide- and sulfur-rich environment at the spring source. Overall, this work indicates that anaerobic metabolic abilities are widely distributed among all major Planctomycetes lineages and suggests carbohydrate fermentation and sulfur reduction as possible mechanisms employed by heterotrophic Planctomycetes for growth and survival under anaerobic conditions. 相似文献
185.
Identification and Isolation of a Castellaniella Species Important during Biostimulation of an Acidic Nitrate- and Uranium-Contaminated Aquifer
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Anne M. Spain Aaron D. Peacock Jonathan D. Istok Mostafa S. Elshahed Fares Z. Najar Bruce A. Roe David C. White Lee R. Krumholz 《Applied microbiology》2007,73(15):4892-4904
Immobilization of uranium in groundwater can be achieved through microbial reduction of U(VI) to U(IV) upon electron donor addition. Microbial community structure was analyzed in ethanol-biostimulated and control sediments from a high-nitrate (>130 mM), low-pH, uranium-contaminated site in Oak Ridge, TN. Analysis of small subunit (SSU) rRNA gene clone libraries and polar lipid fatty acids from sediments revealed that biostimulation resulted in a general decrease in bacterial diversity. Specifically, biostimulation resulted in an increase in the proportion of Betaproteobacteria (10% of total clones in the control sediment versus 50 and 79% in biostimulated sediments) and a decrease in the proportion of Gammaproteobacteria and Acidobacteria. Clone libraries derived from dissimilatory nitrite reductase genes (nirK and nirS) were also dominated by clones related to Betaproteobacteria (98% and 85% of total nirK and nirS clones, respectively). Within the nirK libraries, one clone sequence made up 59 and 76% of sequences from biostimulated sediments but only made up 10% of the control nirK library. Phylogenetic analysis of SSU rRNA and nirK gene sequences from denitrifying pure cultures isolated from the site indicate that all belong to a Castellaniella species; nearly identical sequences also constituted the majority of biostimulated SSU rRNA and nirK clone libraries. Thus, by combining culture-independent with culture-dependent techniques, we were able to link SSU rRNA clone library information with nirK sequence data and conclude that a potentially novel Castellaniella species is important for in situ nitrate removal at this site. 相似文献
186.
Redouane Rouas Makram Merimi Mehdi Najar Nabil El Zein Mohammad Fayyad-Kazan Mimoune Berehab Douaa Agha Dominique Bron Arsene Burny Walid Rachidi Bassam Badran Philippe Lewalle Hussein Fayyad-Kazan 《Journal of cellular physiology》2019,234(10):17459-17472
Regulatory T cells (Tregs) are central for maintaining immune balance and their dysfunction drives the expansion of critical immunologic disorders. During the past decade, microRNAs (miRNAs) have emerged as potent regulators of gene expression among which immune-related genes and their immunomodulatory properties have been associated with different immune-based diseases. The miRNA signature of human peripheral blood (PB) CD8+CD25 +CD127 low Tregs has not been described yet. We thus identified, using TaqMan low-density array (TLDA) technique followed by individual quantitative real-time polymerase chain reaction (qRT-PCR) confirmation, 14 miRNAs, among which 12 were downregulated whereas two were upregulated in CD8 +CD25 +CD127 low Tregs in comparison to CD8 +CD25 − T cells. In the next step, microRNA Data Integration Portal (mirDIP) was used to identify potential miRNA target sites in the 3′-untranslated region (3′-UTR) of key Treg cell-immunomodulatory genes with a special focus on interleukin 10 (IL-10) and transforming growth factor β (TGF-β). Having identified potential miR target sites in the 3′-UTR of IL-10 (miR-27b-3p and miR-340-5p) and TGF-β (miR-330-3p), we showed through transfection and transduction assays that the overexpression of two underexpressed miRNAs, miR-27b-3p and miR-340-5p, downregulated IL-10 expression upon targeting its 3′-UTR. Similarly, overexpression of miR-330-3p negatively regulated TGF-β expression. These results highlighted an important impact of the CD8 + Treg mirnome on the expression of genes with significant implication on immunosuppression. These observations could help in better understanding the mechanism(s) orchestrating Treg immunosuppressive function toward unraveling new targets for treating autoimmune pathologies and cancer. 相似文献
187.
Rajapandian Kanagaraj Miguel B. Araujo Rathin Barman Priya Davidar Rahul De Dinesh K. Digal G. V. Gopi A. J. T. Johnsingh Kashmira Kakati Stephanie Kramer‐Schadt Babu R. Lamichhane Salvador Lyngdoh M. D. Madhusudan Muneer Ul Islam Najar Jyotirmayee Parida Narendra M. B. Pradhan Jean‐Philippe Puyravaud R. Raghunath P. P. Abdul Rahim K. Muthamizh Selvan Naresh Subedi Antonio Trabucco Swati Udayraj Thorsten Wiegand Amirtharaj C. Williams Surendra P. Goyal 《Diversity & distributions》2019,25(5):822-838
188.
Tara Fresques Brad Niles Sofia Aronova Huzefa Mogri Taha Rakhshandehroo Ted Powers 《The Journal of biological chemistry》2015,290(3):1395-1403
Complex sphingolipids are important components of eukaryotic cell membranes and, together with their biosynthetic precursors, including sphingoid long chain bases and ceramides, have important signaling functions crucial for cell growth and survival. Ceramides are produced at the endoplasmic reticulum (ER) membrane by a multicomponent enzyme complex termed ceramide synthase (CerS). In budding yeast, this complex is composed of two catalytic subunits, Lac1 and Lag1, as well as an essential regulatory subunit, Lip1. Proper formation of ceramides by CerS has been shown previously to require the Cka2 subunit of casein kinase 2 (CK2), a ubiquitous enzyme with multiple cellular functions, but the precise mechanism involved has remained unidentified. Here we present evidence that Lac1 and Lag1 are direct targets for CK2 and that phosphorylation at conserved positions within the C-terminal cytoplasmic domain of each protein is required for optimal CerS activity. Our data suggest that phosphorylation of Lac1 and Lag1 is important for proper localization and distribution of CerS within the ER membrane and that phosphorylation of these sites is functionally linked to the COP I-dependent C-terminal dilysine ER retrieval pathway. Together, our data identify CK2 as an important regulator of sphingolipid metabolism, and additionally, because both ceramides and CK2 have been implicated in the regulation of cancer, our findings may lead to an enhanced understanding of their relationship in health and disease. 相似文献
189.
Mohamed T. El-Saadony Osama S. F. Khalil Ali Osman Mashaeal S. Alshilawi Ayman E. Taha Salama M. Aboelenin Mustafa Shukry Ahmed M. Saad 《Saudi Journal of Biological Sciences》2021,28(8):4581-4591
This study aimed to prolong the raw buffalo milk handling and cold storage period by controlling the microbes, enhancing sensory properties and their functionality after supplementing bioactive peptides. The additions included hen and duck egg white protein isolates (HPI and DPI), pepper seed protein (PSP), and pepsin-kidney bean protein hydrolysate (PKH). Five milk treatments were prepared and evaluated as non-supplemented milk (M- Control), hen egg white protein isolate-supplemented milk (M-HPI), duck egg white protein isolate-supplemented milk (M-DPI), pepper seeds protein-supplemented milk (M-PSP), and kidney bean hydrolysate-supplemented milk (M-PKH). Pyrogallol, protocatechuic, catechin, benzoic and caffeine were the main phenolic compounds, Apignin-6-arabinose, naringin, hesperidin, naringenin, kaempferol 3–2-p-comaroyl were the dominant flavonoids in milk samples based on HPLC profile. During 30 days of cold storage, the antioxidant potential of peptides-supplemented milk samples was significantly decreased (p ≤ 0.05) as decrement of phenolic compounds and flavonoids; the pH was nearly stable, the titratable acidity and total soluble solids (TTS) were (p ≤ 0.05) raised. PSP and PKH were inhibited (p ≤ 0.05) the decay of sugars in M-PSP, and M-PKH by reducing 45% of bacterial load as compared to other milk samples. PSP was significantly (p ≤ 0.05) scavenged 87% of DPPḢ compared to other peptides. Besides, PSP followed by PKH reduced considerably (p ≤ 0.05) the growth of tested bacteria, molds, and yeasts. The PSP has significantly increased the whiteness of M-PSP as compared to other milk samples. M-PSP had the highest score in color, taste, and flavor, followed by M-PKH. 相似文献
190.