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61.
The purpose of this study was to develop a drug-loaded nanosystem that has the ability to achieve flexible yet rate-controlled
release of model drug isoniazid (INH) employing either an aqueous or emulsion-based salting-out approach. Formulation conditions
were aimed at reducing the polymeric size with subsequent rate-modulated INH release patterns from the polymeric nanosystem.
The emulsion-based salted-out nanosystems had particle sizes ranging from 77–414 nm and a zeta potential of −24 mV. The dispersant
dielectric constant was set at 78.5 and a conductivity of 3.99 mS/cm achieved. The reduced nanosystem size of the aqueous-based
approach has demonstrated an intrinsically enhanced exposure of methacrylic acid-ethyl acrylate to zinc sulphate which was
employed as a crosslinking reagent. This resulted in robustly interconnected polymeric supports in which INH was efficiently
embedded and subsequently released. The multi-layer perceptron data obtained showed that the aqueous and emulsion-based salting
out approaches had Power (law) (MSE = 0.020) and Linear (MSE = 0.038) relationships, respectively. Drug release from the nanosystems
occurred in two phases with an initial burst-release in aqueous-based nanosystems (30–100%) and significantly lower bursts
observed in emulsion-based nanosystems (20–65%) within the first 2 h. This was followed by a gradual exponential release phase
over the remaining 12 h. The nanosystems developed demonstrated the ability to control the release of INH depending on the
formulation approach adopted. 相似文献
62.
Dorgan KM Wooderchak WL Wynn DP Karschner EL Alfaro JF Cui Y Zhou ZS Hevel JM 《Analytical biochemistry》2006,350(2):249-255
Modification of small molecules and proteins by methyltransferases affects a wide range of biological processes. Here, we report an enzyme-coupled continuous spectrophotometric assay to quantitatively characterize S-adenosyl-L-methionine (AdoMet/SAM)-dependent methyltransferase activity. In this assay, S-adenosyl-L-homocysteine (AdoHcy/SAH), the transmethylation product of AdoMet-dependent methyltransferases, is hydrolyzed to S-ribosylhomocysteine and adenine by recombinant S-adenosylhomocysteine/5'-methylthioadenosine nucleosidase (SAHN/MTAN, EC 3.2.2.9). Subsequently, adenine generated from AdoHcy is further hydrolyzed to hypoxanthine and ammonia by recombinant adenine deaminase (EC 3.5.4.2). This deamination is associated with a decrease in absorbance at 265 nm that can be monitored continuously. Coupling enzymes are recombinant and easily purified. The utility of this assay was shown using recombinant rat protein arginine N-methyltransferase 1 (PRMT1, EC 2.1.1.125), which catalyzes the mono- and dimethylation of guanidino nitrogens of arginine residues in select proteins. Using this assay, the kinetic parameters of PRMT1 with three synthetic peptides were determined. An advantage of this assay is the destruction of AdoHcy by AdoHcy nucleosidase, which alleviates AdoHcy product feedback inhibition of S-adenosylmethionine-dependent methyltransferases. Finally, this method may be used to assay other enzymes that produce AdoHcy, 5'-methylthioadenosine, or compounds that can be cleaved by AdoHcy nucleosidase. 相似文献
63.
Tslil Gabrieli Yael Michaeli Sigal Avraham Dmitry Torchinsky Sapir Margalit Leonie Schütz Matyas Juhasz Ceyda Coruh Nissim Arbib Zhaohui Sunny Zhou Julie
A Law Elmar Weinhold Yuval Ebenstein 《Nucleic acids research》2022,50(16):e92
DNA methylation, specifically, methylation of cytosine (C) nucleotides at the 5-carbon position (5-mC), is the most studied and significant epigenetic modification. Here we developed a chemoenzymatic procedure to fluorescently label non-methylated cytosines in CpG context, allowing epigenetic profiling of single DNA molecules spanning hundreds of thousands of base pairs. We used a CpG methyltransferase with a synthetic S-adenosyl-l-methionine cofactor analog to transfer an azide to cytosines instead of the natural methyl group. A fluorophore was then clicked onto the DNA, reporting on the amount and position of non-methylated CpGs. We found that labeling efficiency was increased up to 2-fold by the addition of a nucleosidase, presumably by degrading the inactive by-product of the cofactor after labeling, preventing its inhibitory effect. We used the method to determine the decline in global DNA methylation in a chronic lymphocytic leukemia patient and then performed whole-genome methylation mapping of the model plant Arabidopsis thaliana. Our genome maps show high concordance with published bisulfite sequencing methylation maps. Although mapping resolution is limited by optical detection to 500–1000 bp, the labeled DNA molecules produced by this approach are hundreds of thousands of base pairs long, allowing access to long repetitive and structurally variable genomic regions. 相似文献
64.
Chiranjit Chowdhury Sunny Chun Michael R. Sawaya Todd O. Yeates Thomas A Bobik 《Molecular microbiology》2016,101(5):770-783
Bacterial microcompartments (MCPs) are complex organelles that consist of metabolic enzymes encapsulated within a protein shell. In this study, we investigate the function of the PduJ MCP shell protein. PduJ is 80% identical in amino acid sequence to PduA and both are major shell proteins of the 1,2‐propanediol (1,2‐PD) utilization (Pdu) MCP of Salmonella. Prior studies showed that PduA mediates the transport of 1,2‐PD (the substrate) into the Pdu MCP. Surprisingly, however, results presented here establish that PduJ has no role 1,2‐PD transport. The crystal structure revealed that PduJ was nearly identical to that of PduA and, hence, offered no explanation for their differential functions. Interestingly, however, when a pduJ gene was placed at the pduA chromosomal locus, the PduJ protein acquired a new function, the ability to mediate 1,2‐PD transport into the Pdu MCP. To our knowledge, these are the first studies to show that that gene location can determine the function of a MCP shell protein. We propose that gene location dictates protein‐protein interactions essential to the function of the MCP shell. 相似文献
65.
66.
The effects of administration of cortisol, corticosterone, testosterone, progesterone and a synthetic estrogen. diethylstilbestrol (DES) on total brain Na(+)-K+- ATPase were investigated in tilapia, O. mossambicus. Exogenous administration of 0.125 and 0.25 microg/g body weight of glucocorticoids and 0.125, 0.25 and 0.5 microg/g body weight of DES for 5 days significantly stimulated Na+(-) K+ ATPase activity by 14-41% in the brain, while 0.5 microg/g body weight of glucocorticoids did not evoke any response on the activity of the enzyme. Progesterone (0.125 and 0.25 microg/g body weight) administration significantly decreased the enzyme activity by 21-36% and high dose (0.5 microg/g body weight) was ineffective. Testosterone exhibited a biphasic effect on Na(+)-K+ ATPase activity--a low dose stimulated by 14% while middle and high doses inhibited it by 19-24%. The results seem to be the first report on the effect of steroids on brain ATPase activity in a teleost. When 0.25microg/g body weight of actinomycin D or puromycin was administered prior to the treatment of similar doses of hormones, the inhibitors significantly inhibited the effect of the hormones by 24-52%. This clearly shows that the effect of the hormones was sensitive to the action of inhibitors suggesting a possible genomic mode of action under long-term treatment. The results suggest that cortisol, corticosterone and DES may possibly stimulate the co-transport of glucose and excitation of membrane potential while progesterone and testosterone inhibit them in the brain of O. mossambicus by regulating the activity of Na(+)-K+ ATPase. 相似文献
67.
68.
González-Fernández Andrea Segarra Joel Sunny Armando Couturier Stephane 《Biodiversity and Conservation》2022,31(3):871-894
Biodiversity and Conservation - In 2013, the protection status of the Nevado de Toluca Volcano was changed from National Park to a less restrictive category. Much controversy has arisen surrounding... 相似文献
69.
Parastenocypris goddeerisi n.sp. and P. achandii n.sp. are described from temporary habitats in Kerala, southern India. The morphology of both males and females is illustrated
and the new species are compared to the known representatives of the genus. Stenocypris fernandoi Neale, described from Sri Lanka, is here referred to Parastenocypris. 相似文献
70.