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1.
J Am Chem Soc ; 145(4): 2219-2229, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36656821

RESUMO

Bioorthogonal click-and-release reactions are powerful tools for chemical biology, allowing, for example, the selective release of drugs in biological media, including inside animals. Here, we developed two new families of iminosydnone mesoionic reactants that allow a bioorthogonal release of electrophilic species under physiological conditions. Their synthesis and reactivities as dipoles in cycloaddition reactions with strained alkynes have been studied in detail. Whereas the impact of the pH on the reaction kinetics was demonstrated experimentally, theoretical calculations suggest that the newly designed dipoles display reduced resonance stabilization energies compared to previously described iminosydnones, explaining their higher reactivity. These mesoionic compounds react smoothly with cycloalkynes under physiological, copper-free reaction conditions to form a click pyrazole product together with a released alkyl- or aryl-isocyanate. With rate constants up to 1000 M-1 s-1, this click-and-release reaction is among the fastest described to date and represents the first bioorthogonal process allowing the release of isocyanate electrophiles inside living cells, offering interesting perspectives in chemical biology.


Assuntos
Cicloparafinas , Animais , Reação de Cicloadição , Alcinos/química , Química Click , Azidas/química
2.
Lab Chip ; 22(23): 4729-4734, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36367074

RESUMO

Hot embossing is a cost-effective and flexible fabrication technology with high replication accuracy for feature sizes as small as 50 nm. Here we develop a reinforced polydimethylsiloxane (PDMS) mold for hot embossing of cyclic olefin polymer (COP) sheets in the fabrication of microfluidic chips and demonstrate the method by fabricating chips for automated sample digitization in digital nucleic acid assays. The PDMS is hardened by adding an investment powder as a dopant and is constrained with an aluminum frame to prevent lateral expansion during hot pressing. The reinforced PDMS mold demonstrated excellent performance in hot embossing (180 °C, 103 kPa, 5 min) for micropatterning COP sheets, with highly reproducible features as small as 10 µm (width of draining channel). In contrast, the microscale features were inconsistent and distorted when omitting either the investment powder or frame from the PDMS mold. COP chips were assembled by thermally bonding patterned and unpatterned COP sheets. We tested the performance of the COP chip for automated sample digitization in a digital LAMP assay used to quantify human papillomavirus-18 (HPV-18) DNA. A mixture of nucleic acid amplification reagents was loaded into the main channel of the chip using a syringe pump, then the solution was spontaneously partitioned into chambers (∼0.6 nL), which were then isolated by flowing oil through the chip. The digital LAMP assay produced accurately absolute quantitation of DNA at concentrations ranging from 10 to 1000 copies per µL. The strategy presented here provides a simple, low-cost method to prepare molds for hot embossing, which facilitates rapid validation of microfluidic designs.


Assuntos
Cicloparafinas , Ácidos Nucleicos , Humanos , Microfluídica/métodos , Polímeros , Pós , Dimetilpolisiloxanos
3.
Molecules ; 27(19)2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36234884

RESUMO

Until now, the intermediate responsible for the acyl transfer of a highly enantioselective tetrapeptide organocatalyst for the kinetic resolution of trans-cycloalkane-1,2-diols has never been directly observed. It was proposed computationally that a π-methylhistidine moiety is acylated as an intermediate step in the catalytic cycle. In this study we set out to investigate whether we can detect and characterize this key intermediate using NMR-spectroscopy and mass spectrometry. Different mass spectrometric experiments using a nano-ElectroSpray Ionization (ESI) source and tandem MS-techniques allowed the identification of tetrapeptide acylium ions using different acylation reagents. The complexes of trans-cyclohexane-1,2-diols with the tetrapeptide were also detected. Additionally, we were able to detect acylated tetrapeptides in solution using NMR-spectroscopy and monitor the acetylation reaction of a trans-cyclohexane-1,2-diol. These findings are important steps towards the understanding of this highly enantioselective organocatalyst.


Assuntos
Cicloparafinas , Metilistidinas , Acilação , Álcoois , Catálise , Cicloexanos , Peptídeos , Espectrometria de Massas por Ionização por Electrospray/métodos , Estereoisomerismo
4.
Oxid Med Cell Longev ; 2022: 3322535, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36211814

RESUMO

Major depressive disorder (MDD) is a common mental disorder with high morbidity. Stress negatively affects for MDD development, whereby transport of stress-induced inflammatory mediators to the central nervous system (CNS) is associated with the etiology of mood disorders. Muscone is a pharmacologically active ingredient isolated from musk, with anti-inflammatory and neuroprotective effects. We hypothesized that muscone may ameliorate depression-like behavior by regulating inflammatory responses. To test this hypothesis, we used the chronic restraint stress (CRS) depression model, and CRS mice were treated with muscone (10 mg/kg, i.g., respectively) for 14 days. The effects of the drug on depressive-like behaviors were evaluated via the open field test (OFT), novelty-suppressed feeding test (NSFT), tail suspension test (TST), and forced swimming test (FST). Quantitative reverse transcription-PCR (qRT-PCR) was utilized to assess levels of proinflammatory cytokines (IL-6, TNF-α, COX2, and IL-1) and the anti-inflammatory cytokines (IL-4 and IL-10). We also determined levels of oxidative stress factors (malondialdehyde, superoxide dismutase, and glutathione peroxidase), as well as doublecortin (DCX) expression by immunofluorescence. The results showed that depression-like behavior and inflammatory levels were improved after muscone treatment. Muscone also significantly improved neurogenesis in the CRS mouse hippocampus and decreased oxidative stress in both the central and peripheral nervous systems. In conclusion, this work is the first to demonstrate that muscone has an antidepressant effect using a CRS model. Oxidative stress, neurogenesis, and inflammatory pathways are key factors affected by the drug and may represent new therapeutic targets to treat MDD, in this impact. These results may represent a new therapeutic target for MDD.


Assuntos
Transtorno Depressivo Maior , Fármacos Neuroprotetores , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Comportamento Animal , Ciclo-Oxigenase 2/metabolismo , Cicloparafinas , Depressão/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológico , Proteínas do Domínio Duplacortina , Glutationa Peroxidase/metabolismo , Hipocampo/metabolismo , Mediadores da Inflamação/metabolismo , Interleucina-1 , Interleucina-10/metabolismo , Interleucina-4/metabolismo , Interleucina-6/metabolismo , Malondialdeído/metabolismo , Camundongos , Doenças Neuroinflamatórias , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo , Estresse Psicológico/tratamento farmacológico , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
5.
Anal Chem ; 94(41): 14151-14158, 2022 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-36200347

RESUMO

One of the biggest challenges in membrane protein (MP) research is to secure physiologically relevant structural and functional information after extracting MPs from their native membrane. Amphipathic polymers represent attractive alternatives to detergents for stabilizing MPs in aqueous solutions. The predominant polymers used in MP biochemistry and biophysics are amphipols (APols), one class of which, styrene maleic acid (SMA) copolymers and their derivatives, has proven particularly efficient at MP extraction. In order to examine the relationship between the chemical structure of the polymers and their ability to extract MPs from membranes, we have developed two novel classes of APols bearing either cycloalkane or aryl (aromatic) rings, named CyclAPols and ArylAPols, respectively. The effect on solubilization of such parameters as the density of hydrophobic groups, the number of carbon atoms and their arrangement in the hydrophobic moieties, as well as the charge density of the polymers was evaluated. The membrane-solubilizing efficiency of the SMAs, CyclAPols, and ArylAPols was compared using as models (i) two MPs, BmrA and a GFP-fused version of LacY, overexpressed in the inner membrane of Escherichia coli, and (ii) bacteriorhodopsin, naturally expressed in the purple membrane of Halobacterium salinarum. This analysis shows that, as compared to SMAs, the novel APols feature an improved efficiency at extracting MPs while preserving native protein-lipid interactions.


Assuntos
Bacteriorodopsinas , Cicloparafinas , Carbono , Detergentes/química , Lipídeos , Maleatos/química , Polímeros/química , Poliestirenos/química
6.
J Org Chem ; 87(21): 14580-14587, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36206555

RESUMO

Described is a mild method that merges organophotoredox catalysis with hydrogen atom transfer to enable C-H alkylation of quinoxalin-2(1H)-ones with feedstock aldehydes, amides, alcohols, ethers, or cycloalkanes. This reaction occurred under environmentally benign and external oxidant-free reaction conditions, providing a general and sustainable access to various C3-alkylated quinoxalinone derivatives with broad substituent diversity and good functional group compatibility.


Assuntos
Álcoois , Cicloparafinas , Aldeídos , Hidrogênio , Amidas , Éteres , Quinoxalinas , Alquilação , Catálise
7.
Biochim Biophys Acta Mol Basis Dis ; 1868(12): 166539, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36100155

RESUMO

Muscone is the main active compound of Moschus. In this paper, the cardioprotective effect of Muscone on acute myocardial ischemia (AMI) rats and its potential mechanisms were investigated. AMI rat models were established to evaluate the protective effect and antioxidative function of Muscone on the hearts. Moreover, Western blot analysis was conducted to quantify the phosphorylated PI3K and AKT levels in PI3K/Akt pathway for further investigating the mechanism of Muscone. Results showed that Muscone could markedly lessen the infarct size and myocardial injury, improve cardiac function, inhibit cardiomyocyte apoptosis and down-regulate serum reactive oxygen species level as indicated by the decreased MDA, BNP and c-TnI activities and the increased SOD, GSH-px, CAT activities and the expression of Bax protein. In addition, it was revealed that Muscone notably promoted the phosphorylation of PI3K and AKT. These findings denote that Muscone exerts a protective effect in heart via inhibition of oxidative stress and apoptosis, offering new insights into the treatment of CHD and the clinical application of Muscone.


Assuntos
Cicloparafinas , Isquemia Miocárdica , Transdução de Sinais , Animais , Cicloparafinas/farmacologia , Isquemia Miocárdica/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Proteína X Associada a bcl-2/metabolismo , Proteína X Associada a bcl-2/farmacologia
8.
Annu Int Conf IEEE Eng Med Biol Soc ; 2022: 4131-4134, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-36086103

RESUMO

Neural prostheses are systems that interact with the human nervous system to recover function lost as a result of disease by recording or stimulating neural signals. Neural implants have a variety of components, but among them, designing highly efficient wireless power transmission systems is particularly important. However, there is a problem that it is difficult to design a wireless power transmission system with high transmission efficiency because power transmission efficiency is affected by various coil parameters. In addition, nerve implants are mainly designed based on polymer substrates, but studies have not been conducted on the process of manufacturing coils based on polymer substrates. In this study, to overcome the mentioned problems, an easy and fast manufacturing process was proposed before designing a precise coil on a polymer substrate. Coil was made by manually winding the 200um copper wire, and the coil was packaged using COC. The coil feasibility test was conducted after fabrication to evaluate the performance of fabrication process. It did not fit the expected frequency because the wire was manually wound to make a small size coil. However, the wire wound coil is expected to be more efficient than the coil made through the PCB process, and if the sophistication is supplemented, it can be used as a highly efficient coil for wireless power transmission.


Assuntos
Cicloparafinas , Humanos , Polímeros , Próteses e Implantes
9.
Langmuir ; 38(37): 11392-11405, 2022 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-36069741

RESUMO

Endoscopes are ubiquitous in minimally invasive or keyhole surgeries globally. However, frequent removal of endoscopes from the patient's body due to the lens contaminations results in undesirable consequences. Therefore, a cost-effective process chain to fabricate thermoplastic-based endoscope lenses with superior antifouling and optical properties is proposed in this research. Such multifunctional surface response was achieved by lubricant impregnation of nanostructures. Two types of topographies were produced by femtosecond laser processing of metallic molds, especially to produce single-tier laser-induced periodic surface structures (LIPSS) and two-tier multiscale structures (MS). Then, these two LIPSS and MS masters were used to replicate them onto two thermoplastic substrates, namely polycarbonate and cyclic olefin copolymer, by using hot embossing. Finally, the LIPSS and MS surfaces of the replicas were infiltrated by silicone oils to prepare lubricant-impregnated surfaces (LIS). Droplet sliding tests revealed that the durability of the as-prepared LIS improved with the increase of the lubricant viscosity. Moreover, the single-tier LIPSS replicas exhibited longer-lasting lubricant conservation properties than the MS ones. Also, LIPSS-LIS replicas demonstrated an excellent optical transparency, better than the MS-LIS ones, and almost match the performance of the reference polished ones. Furthermore, the LIPSS-LIS treatment led to superior antifouling characteristics, i.e., regarding fogging, blood adhesion, protein adsorption, and microalgae attachment, and thus demonstrated its high suitability for treating endoscopic lenses. Finally, a proof-of-concept LIPSS-LIS treatment of endoscope lenses was conducted that confirmed their superior multifunctional response.


Assuntos
Incrustação Biológica , Cicloparafinas , Incrustação Biológica/prevenção & controle , Endoscópios , Humanos , Lasers , Lubrificantes , Óleos de Silicone , Propriedades de Superfície
10.
ACS Chem Neurosci ; 13(19): 2913-2923, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-36095282

RESUMO

Since amyloid ß (Aß) oligomers are more cytotoxic than fibrils, various dimer models have been synthesized. We focused on the C-terminal region that could form a hydrophobic core in the aggregation process and identified a toxic conformer-restricted dimer model (E22P,G38DAP-Aß40 dimer) with an l,l-2,6-diaminopimelic acid linker (n = 3) at position 38, which exhibited moderate cytotoxicity. We synthesized four additional linkers (n = 2, 4, 5, 7) to determine the most appropriate distance between the two Aß40 monomers for a toxic dimer model. Each di-Fmoc-protected two-valent amino acid was synthesized from a corresponding dialdehyde or cycloalkene followed by ozonolysis, using a Horner-Wadsworth-Emmons reaction and asymmetric hydrogenation. Then, the corresponding Aß40 dimer models with these linkers at position 38 were synthesized using the solid-phase Fmoc strategy. Their cytotoxicity toward SH-SY5Y cells suggested that the shorter the linker length, the stronger the cytotoxicity. Particularly, the E22P,G38DAA-Aß40 dimer (n = 2) formed protofibrillar aggregates and exhibited the highest cytotoxicity, equivalent to E22P-Aß42, the most cytotoxic analogue of Aß42. Ion mobility-mass spectrometry (IM-MS) measurement indicated that all dimer models except the E22P,G38DAA-Aß40 dimer existed as stable oligomers (12-24-mer). NativePAGE analysis supported the IM-MS data, but larger oligomers (30-150-mer) were also detected after a 24 h incubation. Moreover, E22P,G38DAA-Aß40, E22P,G38DAP-Aß40, and E22P,G38DAZ-Aß40 (n = 5) dimers suppressed long-term potentiation (LTP). Overall, the ability to form fibrils with cross ß-sheet structures was key to achieving cytotoxicity, and forming stable oligomers less than 150-mer did not correlate with cytotoxicity and LTP suppression.


Assuntos
Doença de Alzheimer , Cicloparafinas , Neuroblastoma , Ozônio , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Ácido Diaminopimélico , Humanos , Fragmentos de Peptídeos/metabolismo
11.
Annu Int Conf IEEE Eng Med Biol Soc ; 2022: 4877-4879, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-36086311

RESUMO

Cyclic Olefin Copolymer is emerging as a packaging material for implantable electrodes due to its physical properties such as low water absorption rate and low water vapor permeability. The electrode-tissue interface is often regarded as a major focus of implantable electrodes, but its packaging should also be considered thoroughly since it directly contacts the adjoining body cells. Therefore, eliminating any sharp boundaries or edges around the package would be beneficial to minimize potential inflammatory responses caused by physical/mechanical stresses. To smooth both inner/outer edges of a cyclic olefin copolymer packaging, an optimal UV laser condition was investigated by varying its marking speed and iterations. Clinical relevance - This establishes a method that can selectively smooth the edges around a cyclic olefin copolymer pack-aged implantable electrodes for reduced mechanical mismatch after insertion.


Assuntos
Cicloparafinas , Eletrodos Implantados , Lasers , Luz , Polímeros
12.
Am J Physiol Regul Integr Comp Physiol ; 323(4): R571-R580, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35968898

RESUMO

Muskrat is a small fur animal with a pair of scent glands that can secrete muskrat musk during breeding season. The consensus is muskrat musk functions as a pheromone, but we hypothesized it has a broader role. In previous research, we found the presence of muscone in muskrat musk. To study whether the muscone can affect the apoptosis of muskrat prostate, we carried out the following investigations. Primary muskrat prostate cells were cultured and treated with muscone. Then we drew cell proliferation curves by applying the CCK-8 and used TdT-mediated dUTP nick end labeling (TUNEL) to detect apoptosis. Levels of mRNA transcription and protein expression of Bcl-2 as well as Bax were detected by qRT-PCR and the Western blot. Meanwhile, we collected tissue samples of muskrat prostates and froze sections to analyze the fluorescence signal intensity of BCL-2 and BAX via immunofluorescence. Under the treatment of 30 µmol/L muscone, the proliferation rate of the experimental group exceeded that of the control group, and the proportion of cells undergoing apoptosis was lower in the experimental group. The qRT-PCR and Western blot result showed that, in the experimental group, the ratio of Bcl-2 to Bax mRNA transcription levels increased by 2.85 times and their corresponding protein expression ratio increased by 2.37 times (P < 0.05). Immunofluorescence results were consistent with the cell experiment's results. The fluorescence signal intensity of BCL-2 was higher in the breeding season than nonbreeding season but vice versa for BAX. Based on these results, we speculate that the muscone could regulates prostate development by inhibiting apoptosis.


Assuntos
Arvicolinae , Próstata , Animais , Apoptose , Arvicolinae/fisiologia , Cicloparafinas , Masculino , Feromônios/metabolismo , Próstata/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Mensageiro/metabolismo , Sincalida/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
13.
J Phys Chem A ; 126(36): 6185-6193, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35998622

RESUMO

The conformational landscape of the medium-size cyclic ketone cycloundecanone has been investigated using chirped-pulse Fourier transform microwave spectroscopy and computational calculations. Nine conformations were observed in the rotational spectrum and identified from the comparison of experimental and theoretical rotational constants as well as the observed and predicted types of rotational transitions. All singly substituted 13C isotopologues were observed for the most abundant conformer, which allowed the determination of partial substitution and effective structures. The most abundant conformer dominates the rotational spectrum and is almost 40 times more abundant than the least abundant conformer. Conformational preferences are governed by the combination of transannular H···H and eclipsed HCCH interactions.


Assuntos
Cetonas , Micro-Ondas , Cicloparafinas , Conformação Molecular , Análise Espectral
14.
Mol Neurobiol ; 59(9): 5891-5901, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35809154

RESUMO

Spinal cord injury (SCI) is a devastating neurological disorder that usually damages sensorimotor and autonomic functions. Signaling pathways can play a key role in the repair process of SCI. The plexin-B2 acts as a receptor for angiogenin and mediates ribosomal RNA transcription, influencing cell survival and proliferation. Protein kinase B serine/threonine kinase interacts with angiogenin to form a positive feedback effect. Brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor can induce angiogenin nuclear translocation. Moreover, the BDNF can promote the secretion of angiogenin. Interestingly, all of them can activate the angiogenin/plexin-B2 axis. Muscone has anti-inflammatory and proliferative features as it can inhibit nuclear transcription factor kappa-B (NF-κB) and activate the angiogenin/plexin-B2 axis, thus being significant agent in the SCI repair process. Herein, we review the potential mechanism of angiogenin/plexin-B2 axis activation and the role of muscone in SCI treatment. Muscone may attenuate inflammatory responses and promote neuronal regeneration after SCI.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Traumatismos da Medula Espinal , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Moléculas de Adesão Celular , Cicloparafinas , Humanos , NF-kappa B/metabolismo , Proteínas do Tecido Nervoso/agonistas , Proteínas do Tecido Nervoso/metabolismo , Ribonuclease Pancreático , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
15.
J Org Chem ; 87(13): 8796-8801, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35732004

RESUMO

A nickel-catalyzed tandem Ueno-Stork cyclization is developed to enable stereoselective 1,2-dicarbofunctionalization of cyclic alkenes and efficiently build various bicyclic products. This new protocol does not involve any toxic or difficult-to-remove tin reagent and is scalable and amenable to build all-carbon quaternary centers.


Assuntos
Cicloparafinas , Níquel , Alcenos , Catálise , Ciclização
16.
J Ethnopharmacol ; 296: 115475, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-35718056

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Musk is a representative drug of aroma-relieving traditional Chinese medicine, and it is a commonly used traditional Chinese medicine for the treatment of ischemic stroke. Muscone is the core medicinal component of musk. AIM OF THE STUDY: We sought to identify the target of muscone in the treatment of ischemic stroke using network pharmacology, an animal model of ischemic stroke, and differential proteomics. MATERIALS AND METHODS: The drug targets of muscone in the treatment of ischemic stroke were predicted and analyzed using information derived from sources such as the Traditional Chinese Medicine Systems Pharmacology database and Swiss Target Prediction tool. The animal model of focal cerebral ischemia was established by suture-based occlusion of the middle cerebral artery of rats. The rats were divided into six groups: sham-operated control, model, musk, muscone1, muscone2, and muscone3. Neurological deficit scores were calculated after intragastric administration of musk or muscone. The microcirculation blood flow of the pia mater was detected using a laser speckle blood flow meter. The cerebral infarction rate was detected by 2,3,5-triphenyltetrazolium chloride staining. The necrosis rate of the cerebral cortex and the hippocampal neurons was detected by hematoxylin and eosin staining. Blood-brain barrier damage was detected by the Evans blue method. Quantitative proteomics analysis in the sham-operated control, model, and muscone groups was performed using tandem-mass-tags. Considering fold changes exceeding 1.2 as differential protein expression, the quantitative values were compared among groups by analysis of variance. Furthermore, a protein-protein interaction network was constructed, and differentially expressed proteins were analyzed by gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. RESULTS: Network pharmacology identified 339 targets for the intersection of 17 components of musk and cerebral ischemia-reperfusion injury. The GO and KEGG enrichment items mainly identified regulation of neuronal synaptic structure and transfer function, synaptic neurotransmitters, and receptor activity. Zoopery showed that the model group had a higher behavioral score, cerebral infarction rate, cortical and hippocampal neuron death rate, Evans blue exudation in the brain, and bilateral pia mater microcirculation blood flow differences than the sham-operated control group (P <0.01). Compared with the model group, the behavioral score, infarction rate, hippocampal neuronal mortality, and Evans blue content decreased significantly in the musk, muscone2, and muscone3 groups (P <0.05). Proteomic analysis showed that 160 genes were differentially expressed among the sham-operated control, model, and muscone groups. GO items with high enrichment included neuronal synapses, postsynaptic signal transduction, etc. KEGG items with high enrichment included cholinergic synapses, calcium signaling pathway, dopaminergic synapses, etc. Protein interaction analysis revealed that the top three protein pairs were Ndufa10/Ndufa6, Kcna2/Kcnab2, and Gsk3b/Traf6. CONCLUSIONS: Muscone can reduce neuronal necrosis, protect the blood-brain barrier, and improve the neurological damage caused by cerebral ischemia via molecular mechanisms mainly involving the regulation of neuronal synaptic connections. Muscone is an important active component responsible for the "consciousness-restoring resuscitation" effect of musk on ischemic stroke.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Animais , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Infarto Cerebral , Estado de Consciência , Cicloparafinas , Modelos Animais de Doenças , Azul Evans/uso terapêutico , Ácidos Graxos Monoinsaturados , Infarto da Artéria Cerebral Média/metabolismo , Necrose , Proteômica , Ratos , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/metabolismo
17.
Chem Asian J ; 17(15): e202200466, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35644928

RESUMO

Groups on the upper rim of cavitands can play major roles in the recognition of small molecules. Water-soluble deep cavitands 1, 2 or 3 bearing the walls upper rim of imidazole, urea, and methyl urea, respectively, were synthesized and characterized as hosts of small-molecule guests. The vase forms of 1 or 2 are stabilized through H-bonding to solvent water molecules between adjacent walls. Various small alkyl organic molecules - alcohols, halides, cycloalkane derivatives and heterocycles - are efficiently bound in 1. For n-alcohols (C5 to C12), the -OH end is fixed at the upper rim and the alkyl parts are in the hydrophobic cavity. The longer alcohol guests (C7-C12) show coiling. Cycloalkane guests rotate rapidly on all 3 axes within the host cavity, while heterocycles show orientations placing their heteroatoms near the cavitand rim. Competition studies between alkyl chlorides, bromides and iodides showed preference for binding of iodides in 1. Competition between cavitands for hexyl halide guests halide showed the order 2>1>3.


Assuntos
Cicloparafinas , Água , Álcoois , Éteres Cíclicos , Iodetos , Modelos Moleculares , Resorcinóis , Ureia , Água/química
18.
Chem Rec ; 22(9): e202200130, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35680609

RESUMO

Organofluorine compounds have had an increasing impact in synthetic organic chemistry and pharmaceutical research over the past two decades. Their syntheses and the development of novel synthetic approaches towards versatile fluorinated small molecules have received great interest. Our research team has designed various selective and stereocontrolled methods for the construction of fluorine-containing small molecular entities, involving the transformation of various functionalized cycloalkenes across their ring olefin bond. The synthetic methodologies developed to access various pharmacologically interesting fluorinated derivatives with multiple chiral centers might be valuable protocols for the preparation of other classes of organic compounds as well.


Assuntos
Cicloparafinas , Halogenação , Flúor/química , Compostos Orgânicos , Estereoisomerismo
19.
Anal Chim Acta ; 1205: 339782, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35414388

RESUMO

Some inborn errors of metabolism and other diseases can result in increasing blood ammonium (hyperammonemia episodes), which can cause serious neurological complications in patients or even death. Early diagnosis, follow up and treatment are essential to minimize irreversible damages in brain. Currently, adequate analytical instrumentation for the necessary ammonium bedside determination is not available in all health centers but only in clinical laboratories of reference hospitals. We therefore have developed a low cost and portable potentiometric Point-of-Care microanalyzer (POC) to address this problem. It consists of a cyclic olefin copolymer-based microanalyzer, the size of a credit card and working in continuous flow, which integrates microfluidics, a gas-diffusion module and a potentiometric detection system. The analytical features achieved are a linear range from 30 to 1000 µmol L-1 NH4+, a detection limit of 18 µmol L-1 NH4+ and a required sample volume of 100 µL, which comply with the medical requirements. Plasma and blood samples are analyzed with no significant differences observed between ammonium concentrations obtained with both the proposed microanalyzer and the reference method. This demonstrates the value of the developed POC for bedside clinical applications.


Assuntos
Compostos de Amônio , Cicloparafinas , Humanos , Microfluídica , Sistemas Automatizados de Assistência Junto ao Leito , Potenciometria
20.
J Sep Sci ; 45(12): 2045-2054, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35324077

RESUMO

Cosmetics that have medicinal effects, including anti-inflammatory and antioxidant, have become a daily care routine consumption. The peptide additives, such as carnosine and nicotinamide, were frequently used to realize these medicinal effects. To accomplish rapid and effective quantitation of carnosine and niacinamide in cosmetics, capillary zone electrophoresis was executed in cyclic olefin copolymer microchips having both dynamic and static coatings. The static coating of cyclic olefin copolymer microchannel was constructed from bovine serum albumin adsorption, immobilization, and active site closure, while the dynamic coating was formed by adding surfactant into running buffer of capillary zone electrophoresis. The static coating can improve the hydrophilicity of cyclic olefin copolymer surface and avoid nonspecific peptide adsorption. The dynamic coating of sodium dodecyl sulfate in running buffer proved to be useful in flow velocity adjustment and the column efficiency enhancement in the capillary zone electrophoresis separation channel of the cyclic olefin copolymer microchip device. A separation resolution up to 4.24 on the mixture of carnosine and nicotinamide was obtained. Moreover, an analysis method was established and applied to simultaneous carnosine and nicotinamide determination in a liquid whitening essence and a solid antiglycation pill, and the results were verified by comparison with high-performance liquid chromatography methods, indicating its potential in complex sample analysis.


Assuntos
Carnosina , Cosméticos , Cicloparafinas , Eletroforese Capilar , Niacinamida , Polímeros/química
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