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Phytochemical study on the methanol extract of the leaves of Phyllanthus reticulatus led to the isolation of two new compounds, phyllanreticosides A (1) and B (2) together with ten known ones (3-12). Their chemical structures were determined by HR-ESI-MS, NMR, and ECD spectra in comparison with the literature. Three ellagitannins, phyllanreticoside A (1), corilagin (3), and phyllanthusiin C (4) inhibited lipopolysaccharide(LPS)-induced nitric oxide production in RAW 264.7 cells with IC50 values of 63.2, 83.2, and 5.6 µM, respectively. In addition, compounds 1, 3, and 4 exhibited significantly antimicrobial activity (MICs: 16-128 µg/mL) towards some of seven microbial strains, including Bacillus cereus, Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica, and Candida albicans.
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Phytochemical study on the methanol extract of the stems of Tinospora crispa (L.) Hook.f. & Thomson led to the isolation of thirteen compounds including three undescribed cis-clerodane-type furanoditerpenoids (1-3) and ten known ones (4-13). Their chemical structures were determined by IR, HR-ESI-MS, 1D-, and 2D-NMR spectra. Compounds 2-6 and 8 inhibited moderately NO production in LPS activated RAW 264.7 cell with the IC50 values of 83.5, 57.6, 75.3, 78.1, and 74.7 µM, respectively.
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Phytochemical studies on Aphanamixis plants have attracted considerable attention over the past few decades due to the structural diversities and significant biological activities of terpenoids produced by these plants. In the present study, five new acyclic diterpene lactone derivatives, aphanamixionolides A-E (1-5), and three known tirucallane-type triterpenes, namely, piscidinol A (6), hispidone (7), and bourjotinolone A (8), were isolated from the leaves of Aphanamixis polystachya. Their structures were elucidated by comprehensive analyses of HR-ESI-MS and NMR spectroscopic data and by comparison with those reported in the literature. Absolute configurations of the new compounds were determined by experimental and TD-DFT calculated ECD spectra. Compounds 1-8 inhibited NO production with IC50 values of 10.2-37.7 µM, which are comparable to positive control l-NMMA (IC50: 31.5 µM).
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BACKGROUND: Prostate cancer (PCa) is one of the most common malignant tumors of the male urinary system, and its incidence and mortality rates have been increasing worldwide. Benign prostatic hyperplasia (BPH) represents stromal and epithelial cell proliferation in the prostate in elderly males. Abnormal activation of inflammation-related signalling molecules, such as toll-like receptor 4 (TLR4) and Janus kinase/signal transducers and activators of transcription (JAK/STAT) has been linked to the initiation and progression of various human diseases including PCa and BPH. Cylindromatosis (CYLD) gene alterations are associated with PCa progression. In this study, the contribution of CYLD, JAK2, and TLR4 gene variants to PCa and BPH risks and their associations with prostate-specific antigen (PSA) levels, immunophenotype, and clinical features in Vietnamese men were determined. METHODS: A total of 102 patients with PCa, 65 with BPH, and 114 healthy controls were enrolled. The immunophenotype was analyzed by flow cytometry, cytokine secretion by enzyme-linked immunosorbent assay (ELISA), and gene variants by DNA sequencing. RESULTS: Lower levels of transforming growth factor ß (TGF-ß) and higher numbers of CD13+CD117- and CD56+CD25+ cells were observed in the PCa group than in the BPH group. Genetic analysis of the CYLD gene identified five single nucleotide polymorphisms (SNPs), of which c.2351-47 C>T, c.2351-46A>T, and rs1971432171 T>G had significantly higher frequencies in PCa patients than in the control and BPH groups. Sequencing of the TLR4 gene revealed five nucleotide changes, in which the rs2149356 SNP showed an increased risk for both PCa and BPH and the c.331-206 SNP had a reduced risk for PCa. Importantly, the expansion of activated natural killer (NK) cells and higher levels of PSA were found in PCa patients carrying the CT genotype of the CYLD c.2351-47 compared to those with the wild-type genotype. CONCLUSION: Activation of NK cells in CYLD-sensitive PCa patients was associated with serum PSA release and the CYLD c.2351-47 variant may be a significant risk factor for prostatitis in PCa patients.
Assuntos
Enzima Desubiquitinante CYLD , Janus Quinase 2 , Antígeno Prostático Específico , Hiperplasia Prostática , Neoplasias da Próstata , Receptor 4 Toll-Like , Humanos , Masculino , Hiperplasia Prostática/genética , Hiperplasia Prostática/sangue , Neoplasias da Próstata/genética , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/sangue , Receptor 4 Toll-Like/genética , Enzima Desubiquitinante CYLD/genética , Enzima Desubiquitinante CYLD/metabolismo , Antígeno Prostático Específico/sangue , Idoso , Janus Quinase 2/genética , Pessoa de Meia-Idade , Imunofenotipagem , Genótipo , Polimorfismo de Nucleotídeo Único , Estudos de Casos e ControlesRESUMO
Structural imperfections can cause both beneficial and detrimental consequences on the excitonic characteristics of transition metal dichalcogenides (TMDs). Regarding valley selection, structural defects typically promote valley depolarization in monolayer TMDs, but defect healing via an additional growth process can restore valley polarization in vertical heterobilayers (VHs). In this study, we analyzed the valley polarization of center-nucleated and edge-nucleated VHs (WS2/MoS2) grown using a controlled growth process and discovered that defect-related photoluminescence (PL) is strongly suppressed in the center-nucleated VHs due to defect healing. Additionally, we demonstrated that the valley polarization of lower-lying intralayer excitons is more sensitive to the defect density of the sample than to higher-lying intralayer excitons. Despite defect healing in the center-nucleated VHs, the temperature-dependent PL study indicated that valley depolarization of the lower-lying intralayer excitons becomes significant below 100 K because of stronger hybridization of defect states. Also, we conducted a comprehensive study on the excitation intensity dependence to investigate the electron-doping-induced Auger recombination mechanism, which also contributes to valley depolarization of intralayer excitons via regeneration of intervalley trions. Our findings provide valuable insight into the development of VH-based valleytronic devices.
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Eight furostanol glycosides including five undescribed compounds, named tribufurostanosides A-E (1-5), and three known ones (6-8) were isolated from the fruits of Tribulus terrestris L. Their chemical structures were determined by the IR, HR-ESI-MS, 1D-, and 2D-NMR spectra. Furostanols 1-8 significantly inhibited nitric oxide production in LPS activated RAW 264.7â cells with IC50 values ranging from 14.2 to 64.7â µM, compared to that of the positive control compound, dexamethazone (IC50 13.6â µM).
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Alterations in signaling pathways and modulation of cell metabolism are associated with the pathogenesis of cancers, including hepatocellular carcinoma (HCC). Small ubiquitin-like modifier (SUMO) proteins and NF-κB family play major roles in various cellular processes. The current study aims to determine the expression profile of SUMO and NF-κB genes in HCC tumors and investigate their association with the clinical outcome of HCC. The expression of 5 genes - SUMO1, SUMO2, SUMO3, NF-κB p65, and NF-κB p50 - was quantified in tumor and adjacent non-tumor tissues of 58 HBV-related HCC patients by real-time quantitative PCR and was analyzed for the possible association with clinical parameters of HCC. The expression of SUMO2 was significantly higher in HCC tumor tissues compared to the adjacent non-tumor tissues (Pâ =â .01), while no significant difference in SUMO1, SUMO3, NF-κB p65, and NF-κB p50 expression was observed between HCC tumor and non-tumor tissues (Pâ >â .05). In HCC tissues, a strong correlation was observed between the expression of SUMO2 and NF-κB p50, between SUMO3 and NF-κB p50, between SUMO3 and NF-κB p65 (Spearman rhoâ =â 0.83; 0.82; 0.772 respectively; Pâ <â .001). The expression of SUMO1, SUMO2, SUMO3, NF-κB p65, and NF-κB p50 was decreased in grade 3 compared to grades 1 and 2 in HCC tumors according to the World Health Organization grades system. Our results highlighted that the SUMO2 gene is upregulated in tumor tissues of patients with HCC, and is related to the development of HCC, thus it may be associated with the pathogenesis of HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina , Humanos , Carcinoma Hepatocelular/virologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , Neoplasias Hepáticas/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/genética , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Proteína SUMO-1/genética , Proteína SUMO-1/metabolismo , NF-kappa B/metabolismo , Adulto , Fator de Transcrição RelA/metabolismo , Fator de Transcrição RelA/genética , Vírus da Hepatite B/genética , Subunidade p50 de NF-kappa B/genética , Subunidade p50 de NF-kappa B/metabolismo , Idoso , Regulação Neoplásica da Expressão Gênica , Ubiquitinas/genética , Ubiquitinas/metabolismo , Hepatite B/complicações , Hepatite B/genéticaRESUMO
BACKGROUND: Fasciocutaneous free deltoid flaps are used to reconstruct hand, foot, and maxillofacial defects. Although anatomical studies of this flap pedicle have been performed on cadavers, there are no reports on the use of 320-detector row computed tomography angiography (CTA-320) to investigate the deltoid flap pedicle in living humans. This study aimed to investigate the arterial characteristics of the deltoid flap pedicle using the CTA-320 system in living humans. METHODS: Twenty-seven adult Vietnamese patients with 54 healthy deltoid regions underwent CTA-320 to investigate arterial blood supply before clinical free-flap transfer. Two- and three-dimensional reconstruction images of the arterial pedicle were visualized, and clinical reconstruction results were evaluated. RESULTS: The cutaneous vessel branches of the deltoid flap were separated from the posterior circumflex humeral artery (PCHA) and originated from the axillary (77.78%), subscapular (12.96%), and brachial (9.26%) arteries. The PCHA penetrated the quadrangular space in 90.74% of patients. The cutaneous arterial branch was present in the deltoid-triceps groove in 100% of patients. The average diameter and length of the PCHA were 3.38 ± 0.58 and 43.08 ± 6.60 mm, respectively. The average diameter and length of the flap cutaneous branch were 1.49 ± 0.28 and 44.57 ± 4.83 mm, respectively. The findings of CTA-320 were aligned with the intraoperative clinical findings well. All deltoid flaps were successfully free-transferred with good outcomes. CONCLUSION: The CTA-320 is a practical and effective method for investigating deltoid flap pedicles. It enables accurate flap design and harvesting of flaps, thereby enhancing the clinical success of free-flap transfer.
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Launaea sarmentosa, also known as Sa Sam Nam, is a widely used remedy in Vietnamese traditional medicine and cuisine. However, the chemical composition and bioactivity of its essential oil have not been elucidated yet. In this study, we identified 40 compounds (98.6% of total peak area) in the essential oil via GC-MS analysis at the first time. Among them, five main compounds including Thymohydroquinone dimethyl ether (52.4%), (E)-α-Atlantone (9.0%), Neryl isovalerate (6.6%), Davanol D2 (isomer 2) (3.9%), and trans-Sesquisabinene hydrate (3.9%) have accounted for 75.8% of total peak area. The anti-bacterial activity of the essential oil against 4 microorganisms including Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa has also investigated via agar well diffusion assay. The results showed that the essential oil exhibited a strong antibacterial activity against Bacillus subtilis with the inhibition zones ranging from 8.2 to 18.7 mm. To elucidate the anti-bacterial effect mechanism of the essential oil, docking study of five main compounds of the essential oil (Thymohydroquinone dimethyl ether, (E)-α-Atlantone, Neryl isovalerate, Davanol D2 (isomer 2), and trans-Sesquisabinene hydrate) against some key proteins for bacterial growth such as DNA gyrase B, penicillin binding protein 2A, tyrosyl-tRNA synthetase, and dihydrofolate reductase were performed. The results showed that the main constituents of essential oil were highly bound with penicillin binding protein 2A with the free energies ranging -27.7 to -44.8 kcal/mol, which suggests the relationship between the antibacterial effect of essential oil and the affinity of main compounds with penicillin binding protein. In addition, the free energies of main compounds of the essential oil with human cyclooxygenase 1, cyclooxygenase 2, and phospholipase A2, the crucial proteins related with inflammatory response were less than diclofenac, a non-steroidal antiinflammatory drug. These findings propose the essential oil as a novel and promising anti-bacterial and anti-inflammatory medicine or cosmetic products.
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Antibacterianos , Bacillus subtilis , Hemiterpenos , Simulação de Acoplamento Molecular , Óleos Voláteis , Ácidos Pentanoicos , Antibacterianos/farmacologia , Antibacterianos/isolamento & purificação , Antibacterianos/química , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Bacillus subtilis/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Tetra-Hidrofolato Desidrogenase/metabolismo , DNA Girase/metabolismo , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Testes de Sensibilidade Microbiana , Cromatografia Gasosa-Espectrometria de MassasRESUMO
Cassava root rot disease caused by the fungal pathogens Fusarium solani and Lasiodiplodia theobromae produces severe damages on cassava production. This research was conducted to produce and assess silver nanoparticles (AgNPs) synthesized by Trichoderma harzianum for reducing root rot disease. The results revealed that using the supernatants of T. harzianum on a silver nitrate solution changed it to reddish color at 48 h, indicating the formation of AgNPs. Further characterization was identified using dynamic light scattering (DLS) and scanning electron microscope (SEM). DLS supported that the Z-average size is at 39.79 nm and the mean zeta potential is at - 36.5 mV. SEM revealed the formation of monodispersed spherical shape with a diameter between 60-75 nm. The antibacterial action of AgNPs as an antifungal agent was demonstrated by an observed decrease in the size of the fungal colonies using an increasing concentration of AgNPs until the complete inhibition growth of L. theobromae and F. solani at > 58 µg mL-1 and at ≥ 50 µg mL-1, respectively. At in vitro conditions, the applied AgNPs caused a decrease in the percentage of healthy aerial hyphae of L. theobromae (32.5%) and of F. solani (70.0%) compared to control (100%). The SR-FTIR spectra showed the highest peaks in the first region (3000-2800 cm-1) associated with lipids and fatty acids located at 2962, 2927, and 2854 cm-1 in the AgNPs treated samples. The second region (1700-1450 cm-1) consisting of proteins and peptides revealed the highest peaks at 1658, 1641, and 1548 cm-1 in the AgNPs treated samples. The third region (1300-900 cm-1), which involves nucleic acid, phospholipids, polysaccharides, and carbohydrates, revealed the highest peaks at 1155, 1079, and 1027 cm-1 in the readings from the untreated samples. Finally, the observed root rot severity on cassava roots treated with AgNPs (1.75 ± 0.50) was significantly lower than the control samples (5.00 ± 0.00).
Assuntos
Manihot , Nanopartículas Metálicas , Doenças das Plantas , Raízes de Plantas , Prata , Nanopartículas Metálicas/química , Prata/química , Prata/farmacologia , Doenças das Plantas/microbiologia , Manihot/microbiologia , Manihot/química , Raízes de Plantas/microbiologia , Fusarium/efeitos dos fármacos , Antifúngicos/farmacologia , Antifúngicos/química , Hypocreales/metabolismo , Hypocreales/efeitos dos fármacos , Trichoderma/metabolismoRESUMO
Four undescribed spirostan glycosides, (25S)-5α-spirostan- 12-one-2α,3ß-diol-3-O-ß-D-glucopyranosyl-(1â4)-ß-D-galactopyranoside (1), (25S)-5α-spirostan-12-one-2α,3ß-diol-3-O-ß-D-galatopyranosyl-(1â2)-ß-D-glucopyranosyl- (1â4)-ß-D-galactopyranoside (2), (25S)-5α-spirostan-12-one-2α,3ß-diol-3-O-ß-D-glucopyranosyl-(1â2)-[ß-D-glucopyranosyl-(1â3)]-ß-D-glucopyranosyl-(1â4)-ß-D-galactopyranoside (3), and hecogenin 3-O-ß-D-glucopyranosyl-(1â3)-[ß-D-xylopyranosyl-(1â2)]-ß-D-glucopyranosyl-(1â4)-[α-L-rhamnopyranosyl-(1â2)]-ß-D-galactopyranoside (4), together with eleven known compounds (5-15) were isolated from the branches and leaves of Tribulus terrestris. Their chemical structures were established through spectroscopic methods, including HR-ESI-MS, 1D-, and 2D-NMR spectra. Preliminary biological evaluation on NO production inhibitory activity in LPS activated RAW 264.7â cells showed that compoundsâ 1-3, 5, and 6 had significant inhibitory effects with IC50 values ranging from 2.4 to 18.3â µM, compared to that of the positive control compound, dexamethazone (IC50 13.6â µM).
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Glicosídeos , Lipopolissacarídeos , Óxido Nítrico , Folhas de Planta , Espirostanos , Tribulus , Camundongos , Animais , Células RAW 264.7 , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Tribulus/química , Folhas de Planta/química , Glicosídeos/química , Glicosídeos/farmacologia , Glicosídeos/isolamento & purificação , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Espirostanos/química , Espirostanos/isolamento & purificação , Espirostanos/farmacologia , Caules de Planta/química , Relação Estrutura-AtividadeRESUMO
Phytochemical study on the methanol extract of the stem barks of Aphanamixis polystachya led to the isolation of four previously undescribed (1-4) and ten known compounds (5-14). Their chemical structures were elucidated to be 11-methoxysawaranospiroride C (1), 6α,9S,10,13-tetrahydroxymegastigmane-3-one (2), 11-hydroxyaphanamixin B (3), (2Z,6E,13E)-2,6,13-triene-11,15-dihydroxyphytanic acid (4), cinnacasside D (5), cinnacasside E (6), vilsonol F (7), (3S,5R,6S,7E,9R)-3,5,6,9-tetrahydroxy-7-en-megastigmane (8), (3S,5R,6R,7E,9R)-3,6,9,10-tetrahydroxy-7-en-megastigmane (9), citroside A (10), threo-1-(3,4,5-trimethoxyphenyl)-1,2,3-propanetriol (11), 3,4,5-trimethoxyphenyl-1-O-ß-D-glucopyranoside (12), p-coumaric acid (13), ferulic acid (14) by HR-ESI-MS, ECD, 1D-, and 2D-NMR spectra. Compounds 1, 3, 4, and 9 showed NO production inhibitory activity in LPS activated RAW 264.7 cells with IC50 values of 42.0, 67.9, 20.5, and 78.6â µM, respectively, while the remaining compounds were inactive with IC50 values over 100â µM.
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Lipopolissacarídeos , Óxido Nítrico , Casca de Planta , Camundongos , Células RAW 264.7 , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Animais , Casca de Planta/química , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Óxido Nítrico/metabolismo , Caules de Planta/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
In this study, seven new pentacyclic triterpene glycosides, named dendrocinaosides A-G (1-7), and six known ones (8-13) were isolated from the whole plants of Dendrobium officinale. Their structures were determined by analyses of HR-ESI-MS, 1D and 2D NMR spectra. Compounds 1-4, 8, and 9 potentially inhibited α-glucosidase and α-amylase activities with the IC50 values ranging from 31.3 ± 2.2 to 42.4 ± 2.5 µM for anti α-glucosidase and from 36.5 ± 1.8 to 56.4 ± 2.0 µM for anti α-amylase activities, respectively, which were lower than that of the positive control, acarbose, showing IC50 values of 47.1 ± 1.4 µM for anti α-glucosidase and 145.7 ± 2.2 µM for anti α-amylase.
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Stone wool is widely used as an efficient thermal insulator within the construction industry; however, its performance can be significantly impacted by the presence of water vapor. By altering the material's characteristics and effective thermo-physical properties, water vapor can reduce overall efficacy in various environmental conditions. Therefore, understanding water adsorption on stone wool surfaces is crucial for optimizing insulation properties. Through the investigation of interaction between water molecules and calcium aluminosilicate (CAS) phase surfaces within stone wool using density functional theory (DFT), we can gain insight into underlying mechanisms governing water adsorption in these materials. This research aims to elucidate the molecular-level interaction between water molecules and CAS surfaces, which is essential for understanding fundamental properties that govern their adsorption process. Both dissociative and molecular adsorptions were investigated in this study. For molecular adsorption, the adsorption energy ranged from - 84 to - 113 kJ mol - 1 depending on surface orientation. A wider range of adsorption energy ( - 132 to - 236 kJ mol - 1 ) was observed for dissociative adsorption. Molecular adsorption was energetically favored on (010) surfaces while dissociative adsorption was most favorable on (111) surfaces. This DFT study provides valuable insights into the water adsorption behavior on low index surfaces of CAS phase in stone wool, which can be useful for designing effective strategies to manage moisture-related issues in construction materials. Based on these findings, additional research on the dynamics and kinetics of water adsorption and desorption processes of this thermal isolation material is suggested.
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In this study, nine triterpene glycosides including seven previously undescribed compounds (1-7), were isolated from leaves of Cryptolepis buchananii R.Br. ex Roem. and Schult. using various chromatographic methods. The chemical structures of the compounds were elucidated to be 3-O-ß-D-glucopyranosyl-(1 â 6)-ß-D-glucopyranosyluncargenin C 28-O-α-L-rhamnopyranosyl-(1 â 2)-ß-D-glucopyranosyl ester (1), 3-O-ß-D-glucopyranosyl-(1 â 2)-ß-D-glucopyranosyluncargenin C 28-O-α-L-rhamnopyranosyl-(1 â 2)-ß-D-glucopyranosyl ester (2), 3-O-ß-D-glucopyranosyl-(1 â 2)-ß-D-glucopyranosyluncargenin C 28-O-ß-D-glucopyranosyl-(1 â 4)-α-L-rhamnopyranosyl-(1 â 2)-ß-D-glucopyranosyl ester (3), 3-O-ß-D-glucopyranosyl-(1 â 2)-ß-D-glucopyranosylhederagenin 28-O-α-L-rhamnopyranosyl-(1 â 2)-ß-D-glucopyranosyl ester (4), 3-O-ß-D-glucopyranosylarjunolic acid 28-O-α-L-rhamnopyranosyl-(1 â 2)-ß-D-glucopyranosyl ester (5), 3-O-ß-D-glucopyranosyl-(1 â 2)-ß- D-glucopyranosyl-6ß,23-dihydroxyursolic acid 28-O-α-L-rhamnopyranosyl-(1 â 2)-ß-D-glucopyranosyl ester (6), 3-O-ß-D-glucopyranosyl-6ß,23-dihydroxyursolic acid 28-O-α-L-rhamnopyranosyl-(1 â 2)-ß-D-glucopyranosyl ester (7), asiatic acid 28-O-α-L-rhamnopyranosyl-(1 â 2)-ß-D-glucopyranosyl ester (8), and 3-O-ß-D-glucopyranosylasiatic acid 28-O-α-L-rhamnopyranosyl-(1 â 2)-ß-D-glucopyranosyl ester (9), through infrared, high-resolution electrospray ionization mass spectrometry, one- and two-dimensional nuclear magnetic resonance spectral analyses. The isolates inhibited nitric oxide production in lipopolysaccharide-activated RAW 264.7 cells, with half-maximal inhibitory concentration (IC50) values of 18.8-58.5 µM, compared to the positive control compound, dexamethasone, which exhibited an IC50 of 14.1 µM.
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Glicosídeos , Óxido Nítrico , Folhas de Planta , Triterpenos , Triterpenos/química , Triterpenos/farmacologia , Triterpenos/isolamento & purificação , Óxido Nítrico/metabolismo , Glicosídeos/química , Glicosídeos/farmacologia , Glicosídeos/isolamento & purificação , Camundongos , Animais , Estrutura Molecular , Folhas de Planta/química , Células RAW 264.7 , Extratos Vegetais/química , Extratos Vegetais/farmacologiaRESUMO
OBJECTIVE: A growing body of literature suggests that preoperative opioid exposure is an independent predictor of poor outcomes in surgical patients. No outcomes data exist on preoperative opioid use and craniotomies/craniectomies. The objective of this study was to determine the impact of preoperative opioid use on 90-day adverse events after craniotomy or craniectomy. METHODS: A single-center retrospective cohort study of 2445 patients undergoing a craniotomy/craniectomy between January 1, 2013, and October 1, 2018, was conducted. Baseline demographics, pre- and postoperative opioid use (morphine milligram equivalents [MMEs]), and surgical metrics were recorded. Patients were categorized based on whether they took prescription opioids preoperatively, defined as within 1 month of surgery, or were opioid naive. The outcomes were mortality and adverse events 90 days after craniotomy/craniectomy. RESULTS: Overall, 26.6% of patients composed the preoperative opioid group. The median daily MME intake among this group was 34.6 (IQR 14.1-90) MMEs. Lower employment rates (p < 0.001), uninsured status (p = 0.016), and intravenous drug use (p = 0.006) were associated with preoperative opioid use. Preoperative opioid use was associated with increased venous thromboembolism (p = 0.001), acute kidney injury (p = 0.002), acute respiratory failure (p < 0.001), myocardial infarction (p = 0.002), delirium (p < 0.001), and infection (p < 0.001). Preoperative opioid use was an independent predictor of overall 90-day adverse events (OR 1.643, 95% CI 1.289-2.095; p < 0.001) and 90-day mortality (OR 1.690, 95% CI 1.254-2.277; p < 0.001). CONCLUSIONS: Preoperative opioid use was independently associated with 90-day postoperative adverse events and mortality. Opioid use increases vulnerability in craniotomy/craniectomy patients and necessitates close monitoring to improve outcomes.
Assuntos
Analgésicos Opioides , Craniotomia , Complicações Pós-Operatórias , Humanos , Feminino , Masculino , Craniotomia/efeitos adversos , Craniotomia/mortalidade , Analgésicos Opioides/uso terapêutico , Analgésicos Opioides/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/mortalidade , Idoso , Dor Pós-Operatória/tratamento farmacológico , Período Pré-Operatório , Estudos de CoortesRESUMO
A phytochemical study of the aerial parts of Piper mutabile C. DC. revealed seven undescribed compounds [two (2-7')-neolignans and five polyoxygenated cyclohexene glycosides] and six known propenylcatechol derivatives. The chemical structures of the isolated compounds were elucidated by extensive HR-ESI-MS and NMR analyses, as well as comparison with the literature. The absolute configurations of the (2-7')-neolignans were confirmed by GIAO 13C NMR calculations with a sorted training set strategy and TD-DFT calculation ECD spectra. The (2-7')-neolignans and polyoxygenated cyclohexene glycosides are unusual in natural sources. Undescribed neolignans 1 and 2 inhibited NO production in RAW 264.7 cells, with respective IC50 values of 14.4 and 9.5 µM.
Assuntos
Cicloexenos , Glicosídeos , Lignanas , Óxido Nítrico , Compostos Fitoquímicos , Piper , Componentes Aéreos da Planta , Óxido Nítrico/biossíntese , Óxido Nítrico/metabolismo , Óxido Nítrico/antagonistas & inibidores , Células RAW 264.7 , Camundongos , Piper/química , Estrutura Molecular , Componentes Aéreos da Planta/química , Animais , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Lignanas/farmacologia , Lignanas/isolamento & purificação , Lignanas/química , Glicosídeos/farmacologia , Glicosídeos/isolamento & purificação , Glicosídeos/química , Cicloexenos/farmacologia , Cicloexenos/isolamento & purificação , ChinaRESUMO
Cyclooxygenases 1 and 2 (COX-1/2) are enzymes renowned for inducing inflammatory responses through the production of prostaglandins. Thus, the development of COX inhibitors has been a promising approach for identifying compounds with anti-inflammatory potential. In this study, we designed 27 new compounds (1-27) based on the structure of a previously known COX inhibitor, using the Ligand Designer tool. Our aim was to improve the affinity of the compounds with COX enzymes by inducing interactions with residue Arg120 while retaining the good π-π stacking interactions of the chromene-phenyl scaffold. Through screening based on ligand-binding free energy defined by molecular docking simulations and MM/GBSA technique, compounds 9 and 10 were identified as having the highest ability to inhibit COX proteins. The binding affinities of the two compounds with COX-1/2 were superior to those of the original NAI10 compound and the reference drug indomethacin. Our virtual screening suggests that compounds 9 and 10 have a strong ability to inhibit COX-1/2 and thus could be promising candidates for further anti-inflammatory drug studies. In essence, our study underscores the pivotal role of the N-aryl iminocoumarin scaffold in shaping the future landscape of novel anti-inflammatory drug development.
Assuntos
Anti-Inflamatórios , Inibidores de Ciclo-Oxigenase 2 , Simulação de Acoplamento Molecular , Ligantes , Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/químicaRESUMO
Two undescribed triterpenes, syzyfolium A (1) and syzyfolium B (2), together with twelve known compounds, terminolic acid (3), actinidic acid (4), piscidinol A (5), threo-dihydroxydehydrodiconiferyl alcohol (6), lariciresinol-4-O-ß-D-glucoside (7), icariol A2 (8), 14ß,15ß-dihydroxyklaineanone (9), garcimangosone D (10), (+)-catechin (11), myricetin-3-O-α-L-rhamnopyranoside (12), quercitrin (13), and 3, 4, 5-trimethoxyphenyl-(6'-O-galloyl)-O-ß-D-glucopyranoside (14) were isolated from the leaves of Syzygium myrsinifolium. Their chemical structures were determined by IR, HR-ESI-MS, 1D and 2D NMR spectra. Compounds 3 and 4 inhibited significantly α-glucosidase with IC50 values of 23.99 and 36.84, respectively, and compounds 1 and 2 inhibited significantly α-amylase with IC50 values of 35.48 and 43.65â µM, respectively.
Assuntos
Syzygium , Triterpenos , Syzygium/química , alfa-Glucosidases , Extratos Vegetais/farmacologia , Triterpenos/farmacologia , alfa-Amilases , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/químicaRESUMO
BACKGROUND: Dengue is one of the most common diseases in the tropics and subtropics. Whilst mortality is a rare event when adequate supportive care can be provided, a large number of patients get hospitalised with dengue every year that places a heavy burden on local health systems. A better understanding of the support required at the time of hospitalisation is therefore of critical importance for healthcare planning, especially when resources are limited during major outbreaks. METHODS: Here we performed a retrospective analysis of clinical data from over 1500 individuals hospitalised with dengue in Vietnam between 2017 and 2019. Using a broad panel of potential biomarkers, we sought to evaluate robust predictors of prolonged hospitalisation periods. RESULTS: Our analyses revealed a lead-time bias, whereby early admission to hospital correlates with longer hospital stays - irrespective of disease severity. Importantly, taking into account the symptom duration prior to hospitalisation significantly affects observed associations between hospitalisation length and previously reported risk markers of prolonged stays, which themselves showed marked inter-annual variations. Once corrected for symptom duration, age, temperature at admission and elevated neutrophil-to-lymphocyte ratio were found predictive of longer hospitalisation periods. CONCLUSION: This study demonstrates that the time since dengue symptom onset is one of the most significant predictors for the length of hospital stays, independent of the assigned severity score. Pre-hospital symptom durations need to be accounted for to evaluate clinically relevant biomarkers of dengue hospitalisation trajectories.