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Nanoscale Oct 2022Small interfering RNA (siRNA) is ideal for gene silencing through a sequence-specific RNA interference process. The redundancy and complexity of molecular pathways in...
Small interfering RNA (siRNA) is ideal for gene silencing through a sequence-specific RNA interference process. The redundancy and complexity of molecular pathways in cancer create a need for multiplexed targeting that can be achieved with multiplexed siRNA delivery. Here, we delivered multiplexed siRNA with a PSMA-targeted biocompatible dextran nanocarrier to downregulate CD46 and PD-L1 in PSMA expressing prostate cancer cells. The selected gene targets, PD-L1 and CD46, play important roles in the escape of cancer cells from immune surveillance. PSMA, abundantly expressed by prostate cancer cells, allowed the prostate cancer-specific delivery of the nanocarrier. The nanocarrier was modified with acid cleavable acetal bonds for a rapid release of siRNA. Cell imaging and flow cytometry studies confirmed the PSMA-specific delivery of CD46 and PD-L1 siRNA to high PSMA expressing PC-3 PIP cells. Immunoblot, qRT-PCR and flow cytometry methods confirmed the downregulation of CD46 and PD-L1 following treatment with multiplexed siRNA.
Topics: Acetals; B7-H1 Antigen; Cell Line, Tumor; Dextrans; Humans; Male; Prostatic Neoplasms; RNA, Double-Stranded; RNA, Small Interfering
PubMed: 36093754
DOI: 10.1039/d2nr02200a -
Molecules (Basel, Switzerland) Oct 2022Two new compounds, ardisiapunine B () and ardisiapunine C (), were isolated from D. Dietr. Their structures were examined using HR-ESI-MS, IR, (1D, 2D) NMR...
Two new compounds, ardisiapunine B () and ardisiapunine C (), were isolated from D. Dietr. Their structures were examined using HR-ESI-MS, IR, (1D, 2D) NMR spectroscopic analyses, single-crystal X-ray diffraction, and ECD calculation. It was found that the two new compounds belong to unusual oleanane-type triterpenes, with compound bearing an acetal unit and a C-13-C-18 double bond, and compound bearing a C-28 aldehyde group and a C-18-C-19 double bond. The anti-inflammatory properties of compounds and were tested on NO production and cellular morphology using RAW264.7 cells, and their anti-tumor properties were tested on cytotoxic activities, cellular morphology, cell apoptosis, and cell cycle. The results showed that compound exhibited a potent cytotoxicity against HepG2 cell lines with an IC of 12.40 μM. Furthermore, it is possible that compound inhibits cell proliferation by blocking the cell G2/M phase and promoting cell apoptosis. Compound exhibited a potential anti-inflammatory activity by decreasing the production of NO in LPS-stimulated RAW264.7 cells. Comparative analysis of the structures of compounds and revealed that the acetal structure and double bond positions were the main differences between them, and these are presumed to be the main reasons for the extreme differences in their cytotoxicity and anti-inflammatory activities. From these new findings, two promising lead compounds were identified for the future development of potential anti-inflammatory or anti-tumor agents.
Topics: Acetals; Aldehydes; Anti-Inflammatory Agents; Antineoplastic Agents; Lipopolysaccharides; Molecular Structure; Oleanolic Acid; Triterpenes
PubMed: 36235179
DOI: 10.3390/molecules27196641 -
Carbohydrate Research Sep 2011Traditional strategies for oligosaccharide synthesis often require extensive protecting and/or leaving group manipulations between each glycosylation step, thereby... (Review)
Review
Traditional strategies for oligosaccharide synthesis often require extensive protecting and/or leaving group manipulations between each glycosylation step, thereby increasing the total number of synthetic steps while decreasing the efficiency of the synthesis. In contrast, expeditious strategies allow for the rapid chemical synthesis of complex carbohydrates by minimizing extraneous chemical manipulations. Oligosaccharide synthesis by selective activation of one leaving group over another is one such expeditious strategy. Herein, the significant improvements that have recently emerged in the area of the selective activation are discussed. The development of orthogonal strategy further expands the scope of the selective activation methodology. Surveyed in this article, are representative examples wherein these excellent innovations have been applied to the synthesis of various oligosaccharide sequences.
Topics: Acetals; Acylation; Carbohydrate Conformation; Carbohydrate Sequence; Chemistry, Organic; Fluorides; Glycomics; Glycosides; Glycosylation; Halogens; Heparin; Imidoesters; Ionic Liquids; Molecular Sequence Data; Oligosaccharides; Sulfoxides; Thiocyanates
PubMed: 21663897
DOI: 10.1016/j.carres.2011.05.004 -
Journal of Analytical Toxicology Oct 2022Presented is the analysis of four cannabinoid-based products. These products were part of a case involving visual and auditory hallucinations that precipitated the...
Presented is the analysis of four cannabinoid-based products. These products were part of a case involving visual and auditory hallucinations that precipitated the commission of a felony and subsequent arrest. The products were labeled to contain ∆8-tetrahydrocannabinol (∆8-THC) or THC acetate (THC-O-A). Primary reference materials were not available for ∆8-THC-O-A, ∆10-THC-O-A, cannabidiol di-acetate (CBD-di-O-A) or respective deuterated internal standards. THC-O-A and CBD-di-O-A standards were prepared by derivatizing ∆8-THC, ∆9-THC, ∆10-THC, CBD, ∆9-THC-d3 and CBD-d3 using acetic anhydride. The cannabinoid-based products were determined to contain ∆8-THC, ∆8-THC-O-A, ∆9-THC-O-A and CBD-di-O-A and/or other phytocannabinoids using three different analytical techniques. Direct analysis in real-time-time-of-flight mass spectrometry was used for identifying exact masses. A gas chromatograph-mass spectrometer was used for the identification of compounds and to quantitate THC-O-As in the products. A liquid chromatograph-tandem mass spectrometer was used to identify and quantitate phytocannabinoids and CBD-di-O-A in the products. To the authors' knowledge, this is the first case report involving the identification of THC-O-As and CBD-di-O-A in commercially available products. Minimal clinical/pharmacological data is available for these emerging synthetic cannabinoids/novel psychoactive substances.
Topics: Acetates; Acetic Anhydrides; Cannabidiol; Cannabinoids; Dronabinol; Humans
PubMed: 35674405
DOI: 10.1093/jat/bkac036 -
Transports of acetate and haloacetate in Burkholderia species MBA4 are operated by distinct systems.BMC Microbiology Nov 2012Acetate is a commonly used substrate for biosynthesis while monochloroacetate is a structurally similar compound but toxic and inhibits cell metabolism by blocking the...
BACKGROUND
Acetate is a commonly used substrate for biosynthesis while monochloroacetate is a structurally similar compound but toxic and inhibits cell metabolism by blocking the citric acid cycle. In Burkholderia species MBA4 haloacetate was utilized as a carbon and energy source for growth. The degradation of haloacid was mediated by the production of an inducible dehalogenase. Recent studies have identified the presence of a concomitantly induced haloacetate-uptake activity in MBA4. This uptake activity has also been found to transport acetate. Since acetate transporters are commonly found in bacteria it is likely that haloacetate was transported by such a system in MBA4.
RESULTS
The haloacetate-uptake activity of MBA4 was found to be induced by monochloroacetate (MCA) and monobromoacetate (MBA). While the acetate-uptake activity was also induced by MCA and MBA, other alkanoates: acetate, propionate and 2-monochloropropionate (2MCPA) were also inducers. Competing solute analysis showed that acetate and propionate interrupted the acetate- and MCA- induced acetate-uptake activities. While MCA, MBA, 2MCPA, and butyrate have no effect on acetate uptake they could significantly quenched the MCA-induced MCA-uptake activity. Transmembrane electrochemical potential was shown to be a driving force for both acetate- and MCA- transport systems.
CONCLUSIONS
Here we showed that acetate- and MCA- uptake in Burkholderia species MBA4 are two transport systems that have different induction patterns and substrate specificities. It is envisaged that the shapes and the three dimensional structures of the solutes determine their recognition or exclusion by the two transport systems.
Topics: Acetates; Acetic Acid; Biological Transport; Burkholderia; Cell Membrane; Metabolic Networks and Pathways; Transcriptional Activation
PubMed: 23167477
DOI: 10.1186/1471-2180-12-267 -
Oxidative Medicine and Cellular... 2013In Saccharomyces cerevisiae, the chronological lifespan (CLS) is defined as the length of time that a population of nondividing cells can survive in stationary phase. In...
In Saccharomyces cerevisiae, the chronological lifespan (CLS) is defined as the length of time that a population of nondividing cells can survive in stationary phase. In this phase, cells remain metabolically active, albeit at reduced levels, and responsive to environmental signals, thus simulating the postmitotic quiescent state of mammalian cells. Many studies on the main nutrient signaling pathways have uncovered the strong influence of growth conditions, including the composition of culture media, on CLS. In this context, two byproducts of yeast glucose fermentation, ethanol and acetic acid, have been proposed as extrinsic proaging factors. Here, we report that ethanol and acetic acid, at physiological levels released in the exhausted medium, both contribute to chronological aging. Moreover, this combined proaging effect is not due to a toxic environment created by their presence but is mainly mediated by the metabolic pathways required for their utilization as carbon/energy sources. In addition, measurements of key enzymatic activities of the glyoxylate cycle and gluconeogenesis, together with respiration assays performed in extreme calorie restriction, point to a long-term quiescent program favoured by glyoxylate/gluconeogenesis flux contrary to a proaging one based on the oxidative metabolism of ethanol/acetate via TCA and mitochondrial respiration.
Topics: Acetates; Ethanol; Saccharomyces cerevisiae
PubMed: 24062879
DOI: 10.1155/2013/802870 -
Journal of the American Chemical Society Nov 2022Aziridines are readily available C(sp) precursors that afford valuable β-functionalized amines upon ring opening. In this article, we report a Ni/photoredox methodology...
Aziridines are readily available C(sp) precursors that afford valuable β-functionalized amines upon ring opening. In this article, we report a Ni/photoredox methodology for C(sp)-C(sp) cross-coupling between aziridines and methyl/1°/2° aliphatic alcohols activated as benzaldehyde dialkyl acetals. Orthogonal activation modes of each alkyl coupling partner facilitate cross-selectivity in the C(sp)-C(sp) bond-forming reaction: the benzaldehyde dialkyl acetal is activated via hydrogen atom abstraction and β-scission via a bromine radical (generated in situ from single-electron oxidation of bromide), whereas the aziridine is activated at the Ni center via reduction. We demonstrate that an Ni(II) azametallacycle, conventionally proposed in aziridine cross-coupling, is not an intermediate in the productive cross-coupling. Rather, stoichiometric organometallic and linear free energy relationship studies indicate that aziridine activation proceeds via Ni(I) oxidative addition, a previously unexplored elementary step.
Topics: Acetals; Catalysis; Benzaldehydes; Nickel; Aziridines
PubMed: 36256882
DOI: 10.1021/jacs.2c09294 -
Experimental Physiology Aug 2009Oral acetate supplementation enhances glycogen synthesis in some mammals. However, while acetate is a significant energy source for skeletal muscle at rest in horses,...
Oral acetate supplementation enhances glycogen synthesis in some mammals. However, while acetate is a significant energy source for skeletal muscle at rest in horses, its effects on glycogen resynthesis are unknown. We hypothesized that administration of an oral sodium acetate-acetic acid solution with a typical grain and hay meal after glycogen-depleting exercise would result in a rapid appearance of acetate in blood with rapid uptake by skeletal muscle. It was further hypothesized that acetate taken up by muscle would be converted to acetyl CoA (and acetylcarnitine), which would be metabolized to CO2 and water via the tricarboxylic acid cycle, generating ATP within the mitochondria and thereby allowing glucose taken up by muscle to be preferentially incorporated into glycogen. Gluteus medius biopsies and jugular venous blood were sampled from nine exercise-conditioned horses on two separate occasions, at rest and for 24 h following a competition exercise test (CET) designed to simulate the speed and endurance test of a 3 day event. After the CETs, horses were allowed water ad libitum and either 8 l of a hypertonic sodium acetate-acetic acid solution via nasogastric gavage followed by a typical hay-grain meal (acetate treatment) or a hay-grain meal alone (control treatment). The CET significantly decreased muscle glycogen concentration by 21 and 17% in the acetate and control treatments, respectively. Acetate supplementation resulted in a rapid and sustained increase in plasma [acetate]. Skeletal muscle [acetyl CoA] and [acetylcarnitine] were increased at 4 h of recovery in the acetate treatment, suggesting substantial tissue extraction of the supplemented acetate. Acetate supplementation also resulted in an enhanced rate of muscle glycogen resynthesis during the initial 4 h of the recovery period compared with the control treatment; however, by 24 h of recovery there was no difference in glycogen replenishment between trials. It is concluded that oral acetate could be an alternative energy source in the horse.
Topics: Acetates; Acetic Acid; Acetyl Coenzyme A; Acetylcarnitine; Animals; Blood Glucose; Exercise Test; Female; Glycogen; Horses; Male; Muscle, Skeletal; Physical Conditioning, Animal; Sodium Acetate
PubMed: 19429643
DOI: 10.1113/expphysiol.2009.047068 -
Yakugaku Zasshi : Journal of the... Nov 2004Burow's solution, or aluminum acetate solution, is effective in inhibiting various microorganisms including methicillin-resistant Staphylococcus aureus (MRSA) that are...
Burow's solution, or aluminum acetate solution, is effective in inhibiting various microorganisms including methicillin-resistant Staphylococcus aureus (MRSA) that are commonly observed in chronic suppurative otitis media. It takes several days to prepare Burow's solution using aluminum sulfate, and the pharmaceutical properties of the solution are not fully understood. In this study, the effect of storage (5 months) of Burow's solution prepared according to the Teine-Keijin Hospital manual on its pharmaceutical properties and antibacterial activities was examined. We also attempted to develop a rapid preparation method of aluminum acetate (or 1.7% aluminum) solution using two commercially available compounds of aluminum acetate basic (Al(2)O(CH(3)CO(2))(4), Al(OH)(CH(3)CO(2))(2)). The properties of Burow's solution, pH, osmolarity and antibacterial activity, were the same among different preparations and its storage for 5 months at 4 degrees C had no effect on these properties. The antibacterial potency of Burow's solution was dependent on aluminum concentration and its antibacterial potency against S. aureus and several MRSA strains was of the same magnitude. In a rapid preparation, aluminum acetate basic was mixed with appropriate amounts of tartaric acid and acetic acid, and the suspension was boiled for 2-2.5 hr until dissolved. The rapidly prepared aluminum acetate solution showed the same pharmaceutical properties and antibacterial activities as those of Burow's solution. The newly developed preparation method for aluminum acetate solution is expected to be convenient and feasible for hospital treatment of chronic suppurative otitis media.
Topics: Acetates; Chemistry, Pharmaceutical; Dose-Response Relationship, Drug; Drug Resistance, Bacterial; Methicillin Resistance; Staphylococcus aureus; Technology, Pharmaceutical
PubMed: 15516810
DOI: 10.1248/yakushi.124.833 -
Organic Letters Apr 2021Sugars are abundant in waste biomass, making them sustainable chiral building blocks for organic synthesis. The demand for chiral saturated heterocyclic rings for...
Sugars are abundant in waste biomass, making them sustainable chiral building blocks for organic synthesis. The demand for chiral saturated heterocyclic rings for pharmaceutical applications is increasing as they provide well-defined three-dimensional frameworks that show increased metabolic resistance. A range of sugar thioacetals can be dehydrated selectively at C-2 under mild basic conditions, and the resulting ketene thioacetals can be applied to the production of useful chiral building blocks via further selective dehydration reactions.
Topics: Acetals; Carbohydrates; Chemistry Techniques, Synthetic; Dehydration; Ethylenes; Ketones; Molecular Structure; Stereoisomerism; Sulfhydryl Compounds
PubMed: 33729808
DOI: 10.1021/acs.orglett.1c00424