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1.
BMC Gastroenterol ; 24(1): 182, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778244

RESUMO

Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) has become the leading cause of chronic liver disease. Liver biopsy, as the diagnostic gold standard, is invasive and has sampling bias, making it particularly important to search for sensitive and specific biomarkers for diagnosis. Cytokeratin 18 (CK18) M30 and M65 are products of liver cell apoptosis and necrosis, respectively, and liver-expressed antimicrobial peptide 2 (LEAP-2) is a related indicator of glucose and lipid metabolism. Correlation studies have found that all three indicators positively correlate with the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Through comparison of diagnostic values, it was found that CK18 M65 can better distinguish between healthy individuals and MAFLD; LEAP-2 can effectively distinguish MAFLD from other liver diseases, especially ALD.


Assuntos
Alanina Transaminase , Aspartato Aminotransferases , Biomarcadores , Queratina-18 , Fígado , Humanos , Queratina-18/sangue , Biomarcadores/sangue , Fígado/patologia , Biópsia , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Peptídeos Catiônicos Antimicrobianos/sangue , Masculino , Pessoa de Meia-Idade , Feminino , Fígado Gorduroso/diagnóstico , Fígado Gorduroso/patologia , Fígado Gorduroso/sangue , Adulto , Sensibilidade e Especificidade , Fragmentos de Peptídeos
2.
Mol Biol Rep ; 51(1): 386, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38441676

RESUMO

BACKGROUND: There was significant difference in muscle development between fat-type and lean-type pig breeds. METHODS AND RESULTS: In current study, transcriptome analysis and bioinformatics analysis were used to compare the difference in longissimus dorsi (LD) muscle at three time-points (38 days post coitus (dpc), 58 dpc, and 78 dpc ) between Huainan (HN) and Large white (LW) pig breeds. A total of 24500 transcripts were obtained in 18 samples, and 2319, 2799, and 3713 differently expressed genes (DEGs) were identified between these two breeds at 38 dpc, 58 dpc, and 78 dpc, respectively. And the number and foldchange of DEGs were increased, the alternative splice also increased. The cluster analysis of DEGs indicated the embryonic development progress of LD muscle between these two breeds was different. There were 539 shared DEGs between HN and LW at three stages, and the top-shared DEGs were associated with muscle development and lipid deposition, such as KLF4, NR4A1, HSP70, ZBTB16 and so on. CONCLUSIONS: The results showed DEGs between Huainan (HN) and Large white (LW) pig breeds, and contributed to the understanding the muscle development difference between HN and LW, and provided basic materials for improvement of meat quality.


Assuntos
Biologia Computacional , Perfilação da Expressão Gênica , Feminino , Gravidez , Suínos/genética , Animais , Análise por Conglomerados , Desenvolvimento Embrionário , Obesidade , Vitaminas
3.
Angew Chem Int Ed Engl ; 62(20): e202301091, 2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-36929860

RESUMO

A cobalt-catalyzed deuteration of amidoacrylates using deuterated methanol afforded α,ß-dideuterio-α-amino esters in excellent enantiomeric ratios (mostly >95 : 5) and almost complete deuteration (99 %). The new protocol was used to prepare dideuterio-α-amino acid fragments in some drugs. Furthermore, the stereoselective deuteration was applied in a concise synthesis of dideuterio l-DOPA.

4.
J Am Chem Soc ; 144(10): 4507-4514, 2022 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-35245025

RESUMO

Multivalent interaction is often used in molecular design and leads to engineered multivalent ligands with increased binding avidities toward target molecules. The resulting binding avidity relies critically on the rigid scaffold that joins multiple ligands as the scaffold controls the relative spatial positions and orientations toward target molecules. Currently, no general design rules exist to construct a simple and rigid DNA scaffold for properly joining multiple ligands. Herein, we report a crystal structure-guided strategy for the rational design of a rigid bivalent aptamer with precise control over spatial separation and orientation. Such a pre-organization allows the two aptamer moieties simultaneously to bind to the target protein at their native conformations. The bivalent aptamer binding has been extensively characterized, and an enhanced binding has been clearly observed. This strategy, we believe, could potentially be generally applicable to design multivalent aptamers.


Assuntos
Aptâmeros de Nucleotídeos , Aptâmeros de Nucleotídeos/química , DNA , Ligantes , Conformação Molecular
5.
Arch Microbiol ; 204(8): 538, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35916974

RESUMO

A Gram-positive, non-motile, non-spore-forming and short rod-shaped actinomycete strain, designated GA224T, was isolated from electronic waste-associated bioaerosols. The optimal growth conditions for this isolate, a facultatively anaerobic bacterium, were 37 °C and pH 8.0. The cell-wall peptidoglycan type was B2γ, with 2,4-diaminobutyric acid (DAB) as the diamino acids, while the major menaquinone was MK-12. The polar lipid profile was composed of diphosphatidylglycerol, phosphatidylglycerol, unidentified phospholipids, unidentified glycolipids and an unidentified lipid. The major cellular fatty acids were anteiso-C15:0 and iso-C16:0. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain GA224T fell within the genus Microcella. The draft genome of strain GA224T comprised 2,495,189 bp with a G + C content of 72.2 mol%. The average nucleotide identity and digital DNA-DNA hybridization values between strain GA224T and the type strain of the type species of Microcella species were lower than 95% and 70%, respectively. Based on the phenotypic, chemotaxonomic and genomic data, strain GA224T represents a novel species, for which the name Microcella aerolata sp. nov. is proposed, with GA224T as the type strain (= GDMCC 1.2165 T = JCM 34462 T).


Assuntos
Actinomycetales , Resíduo Eletrônico , Actinomycetales/genética , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/análise , Fosfolipídeos/análise , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/química
6.
Int J Syst Evol Microbiol ; 72(11)2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36748705

RESUMO

A novel Gram-stain-negative, non-motile, spherical-shaped and facultatively anaerobic bacterial strain, designated as GB24T was isolated from bioaerosols of an E-waste dismantling site in Guiyu, Guangdong Province, South PR China. Growth occurred at 15-40 °C (optimum 37 °C), pH 5.5-9.5 (optimum 7.0), and up to 0.5 % NaCl (w/v) under aerobic conditions, GB24T was characterized taxonomically and phylogenetically. The sole isoprenoid quinone detected was ubiquinone-10 (Q-10). The polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, three unidentified glycolipids, one unidentified phospholipid, and one unidentified aminolipid. Carotenoid pigments were produced. The major cellular fatty acids (> 10 % of total fatty acids) were C17 : 1ω6c (51.5 %) and summed feature 8 (13.5 %, comprising C18 : 1ω7c and/or C18 : 1ω6c). Phylogenetic analysis based on 16S rRNA gene sequence and draft genome grouped strain GB24T into the genus Roseicella. GB24T was most closely related to Roseicella frigidaeris DB1506T with 97.5 % 16S rRNA gene sequence similarity. The draft genome of GB24T comprised 6 153 170 bp with a DNA G+C content of 71.5 %. The average nucleotide identity (ANI) and in silico DNA-DNA hybridization (isDDH) values between GB24T and DB1506T were 83.2 % (Ortho ANI), 83.3 % [ANI by blast (ANIb)] and 27.0 %, respectively. Further genomic analysis of GB24T revealed the secondary metabolite clusters of terpene and phosphonate, which indicate the capacity for malleobactin (14 %) and phosphinothricin (6 %) tripeptide production. On the basis of the genotypic, chemotaxonomic and phenotypic results, GB24T represents a novel species, for which the name Roseicella aerolata sp. nov. is proposed. The type strain of Roseicella aerolata is GB24T (= GDMCC 1.2169T = JCM 34449T).


Assuntos
Resíduo Eletrônico , Ácidos Graxos , Ácidos Graxos/química , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Composição de Bases , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genética , Fosfolipídeos/química , Ubiquinona/química
7.
Bioorg Chem ; 127: 105939, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35700569

RESUMO

Thirty-three novel paeonol etherized aryl urea derivatives (PEUs) were synthesized via a bromination-Williamson Ether Synthesis-deprotection-nucleophilic addition reaction sequence. The structures of PEUs were characterized by LC-MS, HRMS, 1H NMR and 13C NMR spectra. The levels of nitric oxide (NO), tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages were initially employed to evaluate the anti-inflammatory effects of all compounds. Remarkably, b16 exhibited a good anti-inflammatory activity at 2.5 µm which is the same as the potency of paeonol at 20 µm. The results of mechanism research displayed that the anti-inflammatory effect of b16 was ascribed to the inhibition of the TLR4/MyD88 signaling pathway and inflammatory factors. Additionally, b16 distinctly reduced the generation of free radicals in macrophages and strikingly increased the mitochondrial membrane potential. According to the structure-activity relationships (SAR) of PEUs, the incorporation of halogens on the benzene ring and the hydrogen of phenol hydroxyl substituted by aryl urea, were beneficial to enhance the anti-inflammatory activities. Molecular docking results illustrated that the binding ability of b16 to TLR4 was stronger than that of paeonol. In summary, the novel aryl urea-derivied paeonol b16 could be a new promising candidate for the treatment of inflammation-related diseases.


Assuntos
Fator 88 de Diferenciação Mieloide , Receptor 4 Toll-Like , Acetofenonas , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Lipopolissacarídeos/farmacologia , Camundongos , Simulação de Acoplamento Molecular , Fator 88 de Diferenciação Mieloide/metabolismo , Fator 88 de Diferenciação Mieloide/farmacologia , Células RAW 264.7 , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Ureia/farmacologia
8.
BMC Pulm Med ; 22(1): 259, 2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35768814

RESUMO

BACKGROUND: The expression profiles and molecular mechanisms of CXC chemokine receptors (CXCRs) in Lung adenocarcinoma (LUAD) have been extensively explored. However, the comprehensive prognostic values of CXCR members in LUAD have not yet been clearly identified. METHODS: Multiple available datasets, including Oncomine datasets, the cancer genome atlas (TCGA), HPA platform, GeneMANIA platform, DAVID platform and the tumor immune estimation resource (TIMER) were used to detect the expression of CXCRs in LUAD, as well as elucidate the significance and value of novel CXCRs-associated genes and signaling pathways in LUAD. RESULTS: The mRNA and/or protein expression of CXCR1, CXCR2, CXCR3, CXCR4, CXCR5 and CXCR6 displayed predominantly decreased in LUAD tissues as compared to normal tissues. On the contrary, compared with the normal tissues, the expression of CXCR7 was significantly increased in LUAD tissues. Subsequently, we constructed a network including CXCR family members and their 20 related genes, and the related GO functions assay showed that CXCRs connected with these genes participated in the process of LUAD through several signal pathways including Chemokine signaling pathway, Cytokine-cytokine receptor interaction and Neuroactive ligand-receptor interaction. TCGA and Timer platform revealed that the mRNA expression of CXCR family members was significantly related to individual cancer stages, cancer subtypes, patient's gender and the immune infiltration level. Finally, survival analysis showed that low mRNA expression levels of CXCR2 (HR = 0.661, and Log-rank P = 1.90e-02), CXCR3 (HR = 0.674, and Log-rank P = 1.00e-02), CXCR4 (HR = 0.65, and Log-rank P = 5.01e-03), CXCR5 (HR = 0.608, and Log-rank P = 4.80e-03) and CXCR6 (HR = 0.622, and Log-rank P = 1.85e-03) were significantly associated with shorter overall survival (OS), whereas high CXCR7 mRNA expression (HR = 1.604, and Log-rank P = 4.27e-03) was extremely related with shorter OS in patients. CONCLUSION: Our findings from public databases provided a unique insight into expression characteristics and prognostic values of CXCR members in LUAD, which would be benefit for the understanding of pathogenesis, diagnosis, prognosis prediction and targeted treatment in LUAD.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Humanos , Neoplasias Pulmonares/patologia , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
9.
AAPS PharmSciTech ; 22(3): 111, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33748928

RESUMO

Dihydromyricetin (DMY) is highly effective in counteracting acute alcohol intoxication. However, its poor aqueous solubility and permeability lead to the low oral bioavailability and limit its clinic application. The aim of this work is to use Solutol®HS15 (HS 15) as surfactant to develop novel micelle to enhance the oral bioavailability of DMY by improving its solubility and permeability. The DMY-loaded Solutol®HS15 micelles (DMY-Ms) were prepared by the thin-film hydration method. The particle size of DMY-Ms was 13.97 ± 0.82 nm with an acceptable polydispersity index of 0.197 ± 0.015. Upon entrapped in micelles, the solubility of DMY in water was increased more than 25-fold. The DMY-Ms had better sustained release property than that of pure DMY. In single-pass intestinal perfusion models, the absorption rate constant (Ka) and permeability coefficient (Papp) of DMY-Ms were 5.5-fold and 3.0-fold than that of pure DMY, respectively. The relative bioavailability of the DMY-Ms (AUC0-∞) was 205% compared with that of pure DMY (AUC0-∞), indicating potential for clinical application. After administering DMY-Ms, there was much lower blood alcohol level and shorter duration of the loss of righting relax (LORR) in drunk animals compared with that treated by pure DMY. In addition, the oral administration of DMY-Ms greatly reduced oxidative stress, and significantly defended liver and gastric mucosa from alcoholic damages in mice with alcohol-induced tissue injury. Taken together, HS 15-based micelle system greatly improves the bioavailability of DMY and represents a promising strategy for the management of acute alcoholism. Graphical abstract.


Assuntos
Intoxicação Alcoólica/tratamento farmacológico , Flavonóis/administração & dosagem , Flavonóis/uso terapêutico , Intoxicação Alcoólica/patologia , Animais , Área Sob a Curva , Disponibilidade Biológica , Depressores do Sistema Nervoso Central/sangue , Etanol/sangue , Excipientes , Flavonóis/farmacocinética , Mucosa Gástrica/patologia , Hepatite Alcoólica/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Micelas , Nanopartículas , Equilíbrio Postural/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Tensoativos
10.
Yi Chuan ; 43(11): 1066-1077, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34815209

RESUMO

Castration can reduce odor and fights in boars, but the carcass yield is reduced, and the intramuscular fat content is increased. Understanding its molecular mechanism is of great significance for production. Recent studies have shown that circular RNAs (circRNAs) play an important role(s) in the regulation of muscle development. To explore the effects of circRNAs on the development of longissimus dorsi (LD) muscle after castration, six Huainan male pigs were selected and three of which were randomly castrated. Six pigs were slaughtered when their body weight reached around 130 kg, and the LD muscle samples were collected. The differentially expressed circRNAs (DECs) were screened by high-throughput sequencing and functionally analyzed using the KEGG databases. DECs-miRNAs network was constructed, and the expression profiles of candidate circRNAs and their interactions with miRNAs were verified in porcine skeletal muscle satellite cells. The results showed that a total of 5866 circRNAs were obtained, and 370 DECs were identified in LD muscle between the castrated and intact groups (| log2Foldchange | > 1, padj <0.8). KEGG enrichment indicated that the parental genes for the DECs were mainly enriched in the pathways associated with muscle development, muscle fiber type transformation, and energy metabolism. There were 8 miRNAs and 69 circRNAs enriched in the DECs-miRNA network. circRNA_2241 and circRNA_4237 were selected for verification, which showed that these two circRNAs really existed and their expression profiles were consistent with the sequencing results. Further, preliminary analysis showed that circRNA_2241 interacted with miR-1, and testosterone promoted circRNA_2241 but inhibited miR-1 expression. These results confirmed that circRNAs might participate in the regulation of LD muscle development after castration by interacting with miRNAs, thereby providing new materials and references for analyses on the molecular mechanisms of castration on the regulation of muscle development.


Assuntos
MicroRNAs , RNA Circular , Animais , Sequenciamento de Nucleotídeos em Larga Escala , Masculino , MicroRNAs/genética , Desenvolvimento Muscular , Músculos , Suínos/genética
11.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(10): 981-986, 2021 Oct 15.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-34719411

RESUMO

OBJECTIVES: To study the safety and efficacy of dexmedetomidine hydrochloride combined with midazolam in fiberoptic bronchoscopy in children. METHODS: A total of 118 children who planned to undergo fiberoptic bronchoscopy from September 2018 to February 2021 were enrolled. They were divided into a control group (n=60) and an observation group (n=58) using a random number table. The observation group received intravenous pumping of dexmedetomidine hydrochloride (2 µg/mL) at 1 µg/kg and then intravenous injection of midazolam at 0.05 mg/kg, followed by dexmedetomidine hydrochloride pumped intravenously at 0.5-0.7 µg/(kg·h) 10 minutes later to maintain anesthesia. The control group was given intravenous pumping of propofol at 2 mg/kg and then intravenous injection of midazolam at 0.05 mg/kg, followed by propofol pumped intravenously at 4-6 mg/(kg·h) 10 minutes later to maintain anesthesia. Fiberoptic bronchoscopy was performed after the children were unconscious. Heart rate (HR), respiratory rate, blood oxygen saturation, and mean arterial pressure (MAP) were recorded before inserting the bronchoscope (T0), at the time of inserting the bronchoscope (T1), when the bronchoscope reached the glottis (T2), when the bronchoscope reached the carina (T3), and when the bronchoscope entered the bronchus (T4). The intraoperative peak airway pressure (Ppeak), examination time, degree of sedation, extent of amnesia, incidence of adverse reactions, postoperative awakening time, and postoperative agitation score were also recorded. RESULTS: Compared with the control group, the observation group had significantly decreased MAP at T1 to T4 and HR at T1 to T3 (P<0.05). Compared with that at T0, MAP was significantly increased at T1 to T4 in the control group and at T3 in the observation group (P<0.05). HR was significantly higher at T1 to T3 than at T0 (P<0.05). Compared with the control group, the observation group showed significantly lower intraoperative Ppeak value, incidence of intraoperative adverse reactions, and postoperative agitation score, significantly shorter examination time, and better effects of amnesia and anesthesia (P<0.05). There was no significant difference in the degree of intraoperative sedation and postoperative awakening time between the two groups (P>0.05). CONCLUSIONS: Dexmedetomidine hydrochloride combined with midazolam is a safe and effective way to administer general anesthesia for fiberoptic bronchoscopy in children, which can ensure stable vital signs during examination, reduce intraoperative adverse reactions and postoperative agitation, shorten examination time, and increase amnesic effect.


Assuntos
Dexmedetomidina , Midazolam , Brônquios , Broncoscopia , Criança , Dexmedetomidina/efeitos adversos , Humanos , Hipnóticos e Sedativos/efeitos adversos , Estudos Prospectivos
12.
Yi Chuan ; 42(4): 388-402, 2020 Apr 20.
Artigo em Zh | MEDLINE | ID: mdl-32312708

RESUMO

The normal estrus in weaned primiparous sows has a great impact on pig production and abnormal estrus is the main reason for the elimination of primiparous sows. In this study, we studied the long intergenic noncoding RNAs (lincRNAs) in the hypothalamic-pituitary-ovarian axis of anestrous and estrous primiparous sows. These long intergenic noncoding RNAs (lincRNAs) were screened and compared through RNA-seq analysis. The expression profiles of lincRNAs were obtained and their characteristics and functions were preliminarily analyzed. There are 3519 novel lincRNAs identified in the hypothalamic-pituitary-ovarian axis of anestrous and estrous primiparous sows. Compared with estrous primiparous sows, 17 differentially expressed lincRNAs were indentified, including 12 up-regulated lincRNAs and 5 down-regulated lincRNAs (FC≥2, P<0.05). The four lincRNA transcripts obtained through selection were verified by qRT-PCR, which are consistent with the RNA-seq results. The GO, KEGG pathway, and lincRNA-mRNA co-expression network analysis of these 17 lincRNAs revealed that these lincRNAs were mainly involved in reproductive activities, such as oocyte meiosis mature, ovarian cells differentiation and granulosa cells apoptosis. The results enriched the data resources of pig lincRNAs and provided useful information for further research about the reproductive performance of primiparous sows.


Assuntos
Estro/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Ovário/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Feminino , Reprodução , Suínos , Transcriptoma
13.
Molecules ; 23(10)2018 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-30332802

RESUMO

Oxaziridines have emerged as powerful and elegant oxygen- and nitrogen-transfer agents for a broad array of nucleophiles, due to the remarkably high and tunable reactivities. However, the asymmetric catalysis involving oxaziridines is still in its infancy. Herein, this review aims to examine recent advances in the catalytic asymmetric transformations of oxaziridines, including oxidation, amination, cycloaddition and deracemization.


Assuntos
Aziridinas/química , Aminação , Catálise , Reação de Cicloadição , Estrutura Molecular
14.
J Biol Chem ; 291(5): 2087-106, 2016 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-26504080

RESUMO

Tumor invasiveness depends on the ability of tumor cells to breach endothelial barriers. In this study, we investigated the mechanism by which the adhesion of melanoma cells to endothelium regulates adherens junction integrity and modulates tumor transendothelial migration (TEM) by initiating thrombin generation. We found that the B-Raf(V600E) mutation in metastatic melanoma cells up-regulated tissue factor (TF) expression on cell membranes and promoted thrombin production. Co-culture of endothelial monolayers with metastatic melanoma cells mediated the opening of inter-endothelial spaces near melanoma cell contact sites in the presence of platelet-free plasma (PFP). By using small interfering RNA (siRNA), we demonstrated that B-Raf(V600E) and TF silencing attenuated the focal disassembly of adherens junction induced by tumor contact. Vascular endothelial-cadherin (VE-cadherin) disassembly was dependent on phosphorylation of p120-catenin on Ser-879 and VE-cadherin on Tyr-658, Tyr-685, and Tyr-731, which can be prevented by treatment with the thrombin inhibitor, hirudin, or by silencing the thrombin receptor, protease-activated receptor-1, in endothelial cells. We also provided strong evidence that tumor-derived thrombin enhanced melanoma TEM by inducing ubiquitination-coupled VE-cadherin internalization, focal adhesion formation, and actin assembly in endothelium. Confocal microscopic analysis of tumor TEM revealed that junctions transiently opened and resealed as tumor cells accomplished TEM. In addition, in the presence of PFP, tumor cells preferentially transmigrated via paracellular routes. PFP supported melanoma transmigration under shear conditions via a B-Raf(V600E)-thrombin-dependent mechanism. We concluded that the activation of thrombin generation by cancer cells in plasma is an important process regulating melanoma extravasation by disrupting endothelial junction integrity.


Assuntos
Endotélio Vascular/metabolismo , Melanoma/metabolismo , Proteínas Proto-Oncogênicas B-raf/metabolismo , Neoplasias Cutâneas/metabolismo , Trombina/metabolismo , Tromboplastina/metabolismo , Antígenos CD/metabolismo , Caderinas/metabolismo , Adesão Celular , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Movimento Celular , Impedância Elétrica , Inativação Gênica , Células Endoteliais da Veia Umbilical Humana , Humanos , Mutação , Metástase Neoplásica , Permeabilidade , Fosforilação , Plasma/metabolismo , RNA Interferente Pequeno/metabolismo , Ubiquitinação
15.
Org Biomol Chem ; 15(6): 1329-1333, 2017 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-28106218

RESUMO

A convergent and efficient NHC-catalyzed enantioselective tandem Michael addition/lactonization sequence of ynals with 1,2-dione as the dual-nucleophile is disclosed. This straightforward strategy expeditiously assembles the synthetically and pharmaceutically valuable optically active fused dihydropyranones in good to high yields (70-88%) and with excellent enantioselectivities (92-99% ee).

16.
Org Biomol Chem ; 15(22): 4731-4749, 2017 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-28540374

RESUMO

N-Heterocyclic carbenes (NHCs) have emerged as powerful and elegant organocatalysts in a variety of newly developed and unprecedented enantioselective transformations due to their unique umpolung capacity. As a supplement to conventional enantioselective organocatalysis, NHC-induced non-asymmetric catalysis has gradually attracted much interest in recent years. Herein, this review aims to reveal the recent developments in NHC-promoted non-asymmetric umpolung transformations resulting in the expeditious construction of versatile achiral natural heterocycles, carbocycles and acylated products.

17.
Korean J Parasitol ; 53(3): 361-4, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26174833

RESUMO

Gynandromorphic ticks are extremely rare, and often attract parasitologists' attention. During our examination of tick specimens, an engorged gynandromorph of Hyalomma asiaticum was noticed. This is the first record of gynandromorphic ticks from China. In this study, several important morphological structures of normal and gynandromorphic H. asiaticum were analyzed. Comparing to the normal H. asiaticum, the gynandromorphic specimen was a typical bipartite protogynander. Its right side showed normal female characteristics, whereas the left side had normal male traits. Different from other gynandromorphic ticks containing 1 anus, this tick reported here had 2 complete anuses, and the anus of the male part had a single adanal plate.


Assuntos
Quimera/anatomia & histologia , Ixodidae/anatomia & histologia , Doenças dos Ovinos/parasitologia , Infestações por Carrapato/veterinária , Animais , Quimera/genética , China , Feminino , Ixodidae/genética , Masculino , Ovinos , Infestações por Carrapato/parasitologia
18.
Org Lett ; 26(23): 4868-4872, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38832854

RESUMO

A new strategy for facile access to multifunctionalized furans via N-heterocyclic carbene-catalyzed cross-coupling/cyclization of ynenones with aldehydes has been explored. This protocol features readily obtainable starting materials, mild and metal-free conditions, broad substrate scope, good functional group tolerance, excellent yields, and easy scale-up. Synthetic utility of the protocol has been further corroborated through functionalization of complex substrates and postmodifications of the product.

19.
Org Lett ; 25(42): 7745-7750, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37843414

RESUMO

A rhodium-catalyzed carbene N-H insertion protocol for simultaneously controlling the C-N axial and spiro-central chiralities is disclosed, resulting in the rapid assembly of enantiopure N-arylindolinone-spiroacetal derivatives in high yields with excellent enantioselectivities. This promising strategy features the chiral C-N axis, spiro-central chirality, functional group tolerance, and late-stage diversification. DFT calculations indicate that the N-H insertion is the axial-chirality-determining step and that the 1,5-H shift step is regiospecifically caused by the spirocycle.

20.
Pharmaceutics ; 15(9)2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37765265

RESUMO

Intraperitoneal injection of dihydromyricetin (DMY) has shown promising potential in the treatment of alcoholism. However, its therapeutic effect is limited due to its low solubility, poor stability, and high gut-liver first-pass metabolism, resulting in very low oral bioavailability. In this study, we developed a DMY-loaded self-emulsifying drug delivery system (DMY-SEDDS) to enhance the oral bioavailability and anti-alcoholism effect of DMY. DMY-SEDDS improved the oral absorption of DMY by facilitating lymphatic transport. The area under the concentration-time curve (AUC) of DMY in the DMY-SEDDS group was 4.13-fold higher than in the DMY suspension group. Furthermore, treatment with DMY-SEDDS significantly enhanced the activities of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) in the liver of mice (p < 0.05). Interestingly, DMY-SEDDS also increased ADH activity in the stomach of mice with alcoholism (p < 0.01), thereby enhancing ethanol metabolism in the gastrointestinal tract and reducing ethanol absorption into the bloodstream. As a result, the blood alcohol concentration of mice with alcoholism was significantly decreased after DMY-SEDDS treatment (p < 0.01). In the acute alcoholism mice model, compared to saline treatment, DMY-SEDDS prolonged the onset of LORR (loss of righting reflex) (p < 0.05) and significantly shortened the duration of LORR (p < 0.01). Additionally, DMY-SEDDS treatment significantly reduced gastric injury in acute alcoholism mice. Collectively, these findings demonstrate the potential of DMY-SEDDS as a treatment in the treatment of alcoholism.

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