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Soil sustains human life by nourishing crops, storing food sources, and housing microbes, which may affect the nutrition and biosynthesis of secondary metabolites, some of which are used as drugs. To identify lead compounds for a new class of drugs, we collected soil-derived fungal strains from various environments, including urban areas. As various human pathogens are assumed to influence the biosynthetic pathways of metabolites in soil fungi, leading to the production of novel scaffolds, we focused our work on densely populated urban areas and tourist attractions. A soil-derived fungal extract library was screened against MDA-MB-231 cells to derive their cytotoxic activity. Notably, 10 µg/mL of the extract of Trichoderma guizhouense (DS9-1) was found to exhibit an inhibitory effect of 71%. Fractionation, isolation, and structure elucidation efforts led to the identification of nine new peptaibols, trichoguizaibols A-I (1-9), comprising 14 amino acid residues (14-AA peptaibols), and three new peptaibols, trichoguizaibols J-L (10-12), comprising 18 amino acid residues (18-AA peptaibols). The chemical structures of 1-12 were determined based on their 1D and 2D NMR spectra, HRESIMS, electronic circular dichroism data, and results of the advanced Marfey's method. The 18-AA peptaibols were found to exhibit cytotoxicity against MDA-MB-231, SK-Hep1, SKOV3, DU145, and HCT116 cells greater than that of the 14-AA peptaibols. Among these compounds, 10-12 exhibited potent sub-micromolar IC50 values. These results are expected to shed light on a new direction for developing novel scaffolds as anticancer agents.
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The occurrence of autophagy in recombinant Chinese hamster ovary (rCHO) cell culture has attracted attention due to its effects on therapeutic protein production. Given the significance of glycosylation in therapeutic proteins, this study examined the effects of autophagy-inhibiting chemicals on sialylation of Fc-fusion glycoproteins in rCHO cells. Three chemical autophagy inhibitors known to inhibit different stages were separately treated with two rCHO cell lines that produce the same Fc-fusion glycoprotein derived from DUKX-B11 and DG44. All autophagy inhibitors significantly decreased the sialylation of Fc-fusion glycoprotein in both cell lines. The decrease in sialylation of Fc-fusion glycoprotein is unlikely to be attributed to the release of intracellular enzymes, given the high cell viability and low activity of extracellular sialidases. Interestingly, the five intracellular nucleotide sugars remained abundant in cells treated with autophagy inhibitors. In the mRNA expression profiles of 27 N-glycosylation-related genes using the NanoString nCounter system, no significant differences in gene expression were noted. With the positive effect of supplementing nucleotide sugar precursors on sialylation, attempts were made to enhance the levels of intracellular nucleotide sugars by supplying these precursors. The addition of nucleotide sugar precursors to cultures treated with inhibitors successfully enhanced the sialylation of Fc-fusion glycoproteins compared to the control culture. This was particularly evident under mild stress conditions and not under relatively severe stress conditions, which were characterized by a high decrease in sialylation. These results suggest that inhibiting autophagy in rCHO cell culture decreases sialylation of Fc-fusion glycoprotein by constraining the availability of intracellular nucleotide sugars. KEY POINTS: ⢠The autophagy inhibition in rCHO cell culture leads to a significant reduction in the sialylation of Fc-fusion glycoprotein. ⢠The pool of five intracellular nucleotide sugars remained highly abundant in cells treated with autophagy inhibitors. ⢠Supplementation of nucleotide sugar precursors effectively restores decreased sialylation, particularly under mild stress conditions but not in relatively severe stress conditions.
Assuntos
Autofagia , Glicoproteínas , Animais , Cricetinae , Células CHO , Cricetulus , Glicoproteínas/genética , Nucleotídeos , AçúcaresRESUMO
The traditional medicinal mushroom Hericium erinaceus is known for enhancing peripheral nerve regeneration through targeting nerve growth factor (NGF) neurotrophic activity. Here, we purified and identified biologically new active compounds from H. erinaceus, based on their ability to promote neurite outgrowth in hippocampal neurons. N-de phenylethyl isohericerin (NDPIH), an isoindoline compound from this mushroom, together with its hydrophobic derivative hericene A, were highly potent in promoting extensive axon outgrowth and neurite branching in cultured hippocampal neurons even in the absence of serum, demonstrating potent neurotrophic activity. Pharmacological inhibition of tropomyosin receptor kinase B (TrkB) by ANA-12 only partly prevented the NDPIH-induced neurotrophic activity, suggesting a potential link with BDNF signaling. However, we found that NDPIH activated ERK1/2 signaling in the absence of TrkB in HEK-293T cells, an effect that was not sensitive to ANA-12 in the presence of TrkB. Our results demonstrate that NDPIH acts via a complementary neurotrophic pathway independent of TrkB with converging downstream ERK1/2 activation. Mice fed with H. erinaceus crude extract and hericene A also exhibited increased neurotrophin expression and downstream signaling, resulting in significantly enhanced hippocampal memory. Hericene A therefore acts through a novel pan-neurotrophic signaling pathway, leading to improved cognitive performance.
Assuntos
Sistema de Sinalização das MAP Quinases , Memória Espacial , Camundongos , Animais , Transdução de Sinais , Neurônios/metabolismo , Hipocampo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Receptor trkB/metabolismo , Células CultivadasRESUMO
Zaluzanin C (ZC), a sesquiterpene lactone isolated from Laurus nobilis L., has been reported to have anti-inflammatory and antioxidant effects. However, the mechanistic role of ZC in its protective effects in Kupffer cells and hepatocytes has not been elucidated. The purpose of this study was to elucidate the efficacy and mechanism of action of ZC in Kupffer cells and hepatocytes. ZC inhibited LPS-induced mitochondrial ROS (mtROS) production and subsequent mtROS-mediated NF-κB activity in Kupffer cells (KCs). ZC reduced mRNA levels of pro-inflammatory cytokines (Il1b and Tnfa) and chemokines (Ccl2, Ccl3, Ccl4, Cxcl2 and Cxcl9). Tumor necrosis factor (TNF)-α-induced hepatocyte mtROS production was inhibited by ZC. ZC was effective in alleviating mtROS-mediated mitochondrial dysfunction. ZC enhanced mitophagy and increased mRNA levels of fatty acid oxidation genes (Pparα, Cpt1, Acadm and Hadha) and mitochondrial biosynthetic factors (Pgc1α, Tfam, Nrf1 and Nrf2) in hepatocytes. ZC has proven its anti-lipid effect by improving lipid accumulation in hepatocytes by enhancing mitochondrial function to facilitate lipid metabolism. Therefore, our study suggests that ZC may be an effective compound for hepatoprotection by suppressing inflammation and lipid accumulation through regulating mtROS.
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Hepatócitos , Células de Kupffer , Humanos , Células de Kupffer/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Mitocôndrias/metabolismo , RNA Mensageiro/metabolismo , Lipídeos/farmacologia , Fígado , Metabolismo dos LipídeosRESUMO
The secondary metabolites from Hericium erinaceus are well-known to have neurotrophic and neuroprotective effects. Isohericerinol A (1), isolated by our colleagues from its fruiting parts has a strong ability to increase the nerve growth factor secretion in C6 glioma cells. The current work describes the total synthesis of 1 and its regioisomer 5 in a few steps. We present two different approaches to 1 and a regiodivergent approach for both 1 and 5 by utilizing easily accessible feedstocks. Interestingly, the natural product 1, regioisomer 5, and their intermediates exhibited potent neurotrophic activity in in vitro experimental systems. Thus, these synthetic strategies provide access to a systematic structure-activity relationship study of natural product 1.
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Produtos Biológicos , Glioma , Fármacos Neuroprotetores , Produtos Biológicos/farmacologia , Humanos , Fármacos Neuroprotetores/farmacologiaRESUMO
PURPOSE: Central diabetes insipidus is a complication that may occur after pituitary surgery and has been difficult to predict. This study aimed to identify the cutoff levels of serum copeptin and its optimal timing for predicting the occurrence of central diabetes insipidus in patients who underwent transsphenoidal surgery. METHODS: This was a prospective observational study of patients who underwent transsphenoidal surgery for pituitary gland or stalk lesions. Copeptin levels were measured before surgery, 1 h after extubation, and on postoperative days 1, 2, 7, and 90. RESULTS: Among 73 patients, 14 (19.2%) and 13 (17.8%) patients developed transient and permanent central diabetes insipidus, respectively. There was no significant difference in copeptin levels before surgery and 1 h after extubation; copeptin levels on postoperative days 1, 2, 7, and 90 were significantly lower in patients with permanent central diabetes insipidus than in those without central diabetes insipidus. Copeptin measurement on postoperative day 2 exhibited the highest performance for predicting permanent central diabetes insipidus among postoperative days 1, 2, and 7 (area under the curve [95% confidence interval] = 0.754 [0.632-0.876]). Serum copeptin level at postoperative day 2(< 3.1 pmol/L) showed a sensitivity of 92.3% and a negative predictive value of 97.1%. The ratio of copeptin at postoperative day 2 to baseline (< 0.94) presented a sensitivity of 84.6% and a negative predictive value of 94.9%. The copeptin levels > 3.4 and 7.5 pmol/L at postoperative day 2 and 7 may have ruled out the occurrence of CDI with a negative predictive value of 100%. CONCLUSION: The copeptin level at postoperative day 2 and its ratio to baseline can predict the occurrence of permanent central diabetes insipidus after pituitary surgery.
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Diabetes Insípido Neurogênico , Diabetes Mellitus , Doenças da Hipófise , Humanos , Diabetes Insípido Neurogênico/etiologia , Doenças da Hipófise/complicações , Hipófise/cirurgia , Glicopeptídeos , Complicações Pós-Operatórias/epidemiologiaRESUMO
BACKGROUND: Bacterial exposure from house dust has been associated with asthma and atopy in children but whether these relationships are present in adults remains unclear. OBJECTIVE: We sought to examine associations of house dust microbiota with adult asthma, atopy, and hay fever. METHODS: Vacuumed bedroom dust samples from the homes of 879 participants (average age, 62 years) in the Agricultural Lung Health Study, a case-control study of asthma nested within a farming cohort, were subjected to 16S rRNA amplicon sequencing to characterize bacterial communities. We defined current asthma and hay fever using questionnaires and current atopy by blood specific IgE level > 0.70 IU/mL to 1 or more of 10 common allergens. We used linear regression to examine whether overall within-sample bacterial diversity differed by outcome, microbiome regression-based kernel association test to evaluate whether between-sample bacterial community compositions differed by outcome, and analysis of composition of microbiomes to identify differentially abundant bacterial taxa. RESULTS: Overall diversity of bacterial communities in house dust was similar by asthma status but was lower (P < .05) with atopy or hay fever. Many individual bacterial taxa were differentially abundant (false-discovery rate, <0.05) by asthma, atopy, or hay fever. Several taxa from Cyanobacteria, Bacteroidetes, and Fusobacteria were more abundant with asthma, atopy, or hay fever. In contrast, several taxa from Firmicutes were more abundant in homes of individuals with adequately controlled asthma (vs inadequately controlled asthma), individuals without atopy, or individuals without hay fever. CONCLUSIONS: Microbial composition of house dust may influence allergic outcomes in adults.
Assuntos
Asma/microbiologia , Bacteroidetes/fisiologia , Cianobactérias/fisiologia , Poeira/análise , Fusobactérias/fisiologia , Hipersensibilidade Imediata/microbiologia , Microbiota/imunologia , RNA Ribossômico 16S/genética , Rinite Alérgica Sazonal/microbiologia , Idoso , Agricultura , Asma/imunologia , Estudos de Casos e Controles , Poeira/imunologia , Feminino , Interações entre Hospedeiro e Microrganismos , Humanos , Hipersensibilidade Imediata/imunologia , Imunoglobulina E/metabolismo , Masculino , Microbiota/genética , Pessoa de Meia-Idade , Grupos Populacionais , Rinite Alérgica Sazonal/imunologia , Estados UnidosRESUMO
RATIONALE: Genome-wide association studies (GWASs) have identified numerous loci associated with lower pulmonary function. Pulmonary function is strongly related to smoking and has also been associated with asthma and dust endotoxin. At the individual SNP level, genome-wide analyses of pulmonary function have not identified appreciable evidence for gene by environment interactions. Genetic Risk Scores (GRSs) may enhance power to identify gene-environment interactions, but studies are few. METHODS: We analysed 2844 individuals of European ancestry with 1000 Genomes imputed GWAS data from a case-control study of adult asthma nested within a US agricultural cohort. Pulmonary function traits were FEV1, FVC and FEV1/FVC. Using data from a recent large meta-analysis of GWAS, we constructed a weighted GRS for each trait by combining the top (p value<5×10-9) genetic variants, after clumping based on distance (±250 kb) and linkage disequilibrium (r2=0.5). We used linear regression, adjusting for relevant covariates, to estimate associations of each trait with its GRS and to assess interactions. RESULTS: Each trait was highly significantly associated with its GRS (all three p values<8.9×10-8). The inverse association of the GRS with FEV1/FVC was stronger for current smokers (pinteraction=0.017) or former smokers (pinteraction=0.064) when compared with never smokers and among asthmatics compared with non-asthmatics (pinteraction=0.053). No significant interactions were observed between any GRS and house dust endotoxin. CONCLUSIONS: Evaluation of interactions using GRSs supports a greater impact of increased genetic susceptibility on reduced pulmonary function in the presence of smoking or asthma.
Assuntos
Asma , Estudo de Associação Genômica Ampla , Adulto , Asma/genética , Estudos de Casos e Controles , Endotoxinas/toxicidade , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Fumar/efeitos adversosRESUMO
Four compounds, hericerin (1), isohericerinol A (2), N-de-phenylethyl isohericerin (3) and corallocin A (4) were isolated from the fruiting bodies of Hericium erinaceus, a lion's mane mushroom (Hericiaceae). Among them, isohericerinol A (2) was newly reported in nature. Further investigation of the neurotrophic effect of isolated compounds demonstrated that isohericerinol A (2) strongly increased the nerve growth factor (NGF) production in C6 glioma cells followed by corallocin A (4) and hericerin (1). Increased NGF production by these compounds promoted the neurite outgrowth in N2a neuronal cells. Western blot analysis also showed the increased protein expression of NGF, brain-derived neurotrophic factor (BDNF) and synaptophysin (SYP) in C6-N2a cells. Taken together, our present study characterized the neurotrophic constituents of H. erinaceus, which may support the potential use of memory improvement.
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Fator Neurotrófico Derivado do Encéfalo/biossíntese , Carpóforos/química , Hericium/química , Isoindóis/farmacologia , Fator de Crescimento Neural/biossíntese , Sinaptofisina/biossíntese , Animais , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Isoindóis/química , Isoindóis/isolamento & purificação , Simulação de Acoplamento Molecular , Estrutura Molecular , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos , Relação Estrutura-AtividadeRESUMO
Three new guaianolide lactones (1-3) and four new 9-oxonerolidol glucosides (5-8) together with 20 known compounds were isolated from the MeOH extract of the flowers of Chrysanthemum indicum. Their structures were elucidated based on the interpretation of NMR, HRESIMS, and electronic circular dichroism (ECD) data along with acid hydrolysis. Of the isolates, sesquiterpenoids 1-4 and 15 and flavones 17 and 18 exhibited inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide production in RAW 264.7 cells with IC50 values in the range 0.2-27.0 µM.
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Anti-Inflamatórios/farmacologia , Chrysanthemum/química , Sesquiterpenos/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Flavonas/isolamento & purificação , Flavonas/farmacologia , Flores/química , Glucosídeos/isolamento & purificação , Lactonas/isolamento & purificação , Camundongos , Estrutura Molecular , Óxido Nítrico/biossíntese , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Plantas Medicinais/química , Células RAW 264.7 , República da Coreia , Sesquiterpenos/isolamento & purificaçãoRESUMO
Bioactivity-guided isolation of a MeOH extract of Aralia cordata led to the isolation of four new ent-pimarane diterpenoids (1-4) and a diacetylene (5) together with 21 known compounds (6-26). Their structures were established based on the interpretation of one- and two-dimensional NMR and HRESIMS data. The absolute configurations of the new isolates were determined by electronic circular dichroism data analysis, single crystal X-ray diffraction, and Mosher's esterification method. All compounds exhibited inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages with IC50 values ranging from 1.1 to 69.4 µM.
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Alcinos/farmacologia , Aralia/química , Diterpenos/farmacologia , Óxido Nítrico/biossíntese , Alcinos/isolamento & purificação , Animais , Diterpenos/isolamento & purificação , Macrófagos/efeitos dos fármacos , Camundongos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Raízes de Plantas/química , Células RAW 264.7 , República da CoreiaRESUMO
Three new ursane-type triterpenes (1-3) and twenty-one known triterpenoids (4-24) were isolated from the methanolic extract of the whole plants of Potentilla chinensis. Their structures were elucidated by extensive spectroscopic analysis of 1D and 2D NMR (HSQC, HMBC, COSY and ROESY) and HRESIMS data. The bioassay screening revealed the inhibitory effects on nitric oxide production of compounds 2, 5, 7, 9, 10, and 13-24 in LPS-induced RAW264.7 macrophages.
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Óxido Nítrico/antagonistas & inibidores , Triterpenos Pentacíclicos/farmacologia , Potentilla/química , Animais , Relação Dose-Resposta a Droga , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Estrutura Molecular , Óxido Nítrico/biossíntese , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/isolamento & purificação , Células RAW 264.7 , Relação Estrutura-AtividadeRESUMO
Investigation of chemical constituents of Masclura tricuspidata leaves resulted in the isolation of 47 isoflavonoids possessing prenyl groups with different numbers and structures. Among them, sixteen compounds named cudracusisoflavones A-P (1-16) were first isolated from nature. The isoflavonoids isolated from M. tricuspidata leaves showed anti-diabetic effects as measured by inhibition on α-glucosidase activity and advanced glycation end-products (AGEs) formations. Especially, cudracusisoflavone L (12), a new compound, together with gancaonin M (27), erysenegalensein E (41) and millewanin G (44) showed strong α-glucosidase inhibition with IC50 values <10.0 µM. In addition, cudracusisoflavones A (1), D (4), M (13) and N (14), together with known prenylated isoflavonoids efficiently inhibited methylglyoxal (MGO)- or glyoxal (GO)-induced AGE formations. Structure activity relationship together with molecular docking analysis suggested the importance of hydroxy group and linear type of prenyl moiety for α-glucosidase inhibition. Conclusively, diverse prenylated isoflavonoids in M. tricuspidata leaves might ameliorate glycotoxicity-induced metabolic diseases.
Assuntos
Flavonoides/farmacologia , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Inibidores de Glicosídeo Hidrolases/farmacologia , Hipoglicemiantes/farmacologia , Moraceae/química , alfa-Glucosidases/metabolismo , Relação Dose-Resposta a Droga , Flavonoides/química , Flavonoides/isolamento & purificação , Produtos Finais de Glicação Avançada/metabolismo , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Glicosilação/efeitos dos fármacos , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Simulação de Acoplamento Molecular , Estrutura Molecular , Folhas de Planta/química , Saccharomyces cerevisiae/enzimologia , Relação Estrutura-AtividadeRESUMO
BACKGROUND: To explore the association of thrombo-inflammatory biomarkers with severity in coronavirus disease (COVID-19), we measured antiphospholipid antibodies (aPL) and calprotectin in sera of COVID-19 patients. METHODS: Anticardiolipin antibodies (aCL) and anti-ß2-glycoprotein I antibodies were measured using enzyme-linked immunosorbent assay (ELISA) and multiplex flow immunoassay (MFIA) in hospitalized COVID-19 patients (N = 105) and healthy controls (N = 38). Anti-phosphatidylserine/prothrombin antibodies, calprotectin, and C-reactive protein (CRP) levels were also measured. We assessed the potential correlation between calprotectin levels and various laboratory parameters that were measured during the hospitalization period. After stratifying COVID-19 patients into two groups by their oxygenation status or acute respiratory distress syndrome presentation, the discriminatory performance of each biomarker was evaluated. RESULTS: A high proportion of COVID-19 patients (29.5%, 31/105) had low aCL IgM titers that were detectable by ELISA but mostly below the detection limit of MFIA. Calprotectin levels in severe groups of COVID-19 were significantly higher than those in non-severe groups, while CRP levels revealed no significant differences. Serum calprotectin levels showed strong to moderate degree of correlation with other routinely used parameters including peak levels of CRP, ferritin, procalcitonin, BUN, and neutrophil-to-lymphocyte ratio, but a negative correlation with minimal lymphocyte count and CD4+ T cells. The discriminatory performance was highest for calprotectin in discriminating severe groups of COVID-19. CONCLUSIONS: Serum calprotectin levels were significantly elevated in severe COVID-19 cases. The prevalence of clinically significant aPL did not differ. The link between calprotectin and inflammatory pathway in COVID-19 may help improve the management and outcomes of COVID-19 patients.
Assuntos
Anticorpos Antifosfolipídeos/sangue , COVID-19/sangue , Complexo Antígeno L1 Leucocitário/sangue , SARS-CoV-2 , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Proteína C-Reativa/análise , COVID-19/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
Vitis amurensis roots have been reported to have the potential for skin whitening through the evaluation of melanogenesis and tyrosinase inhibitory activities. In this study, V. amurensis roots were utilized to quickly select whitening ingredients using LC-Q-TOF-MS coupled with tyrosinase inhibitory assay, and to optimize the extraction process for use as a skin whitening functional material by response surface methodology. Results showed that V. amurensis roots exhibited tyrosinase inhibitory effects by two stilbene oligomers, ε-viniferin (1) and vitisin B (2), as predicted by LC-Q-TOF-MS coupled with bioassay. The optimal extraction conditions (methanol concentration 66%, solvent volume 140 mL, and extraction time 100 min) for skin whitening ingredients were established with the yields 6.20%, and tyrosinase inhibitory activity was 87.27%. The relationship between each factor and its corresponding response was confirmed by Pearson's correlation analysis. The solvent volume showed clear linear relationship with yields, and methanol concentration had a strong linear relationship with tyrosinase inhibitory activity for compounds 1 and 2, as well as their combination. Overall, LC-Q-TOF-MS coupled with bioassay was proved to have the potential to effectively find new active constituents, as well as known active constituents; vitisin B can be proposed as a new natural potential whitening agent.
Assuntos
Benzofuranos/química , Bioensaio , Inibidores Enzimáticos/química , Monofenol Mono-Oxigenase , Fenóis/química , Raízes de Plantas/química , Estilbenos/química , Vitis/química , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/químicaRESUMO
Streptococcus zoonotic bacteria cause serious problems in aquaculture with clinical effects on humans. A structure-antibacterial activity relationships analysis of 22 isoflavones isolated from M. tricuspidata (leaves, ripe fruits, and unripe fruits) against S. iniae revealed that prenylation of the isoflavone skeleton was an important key for their antibacterial activities (minimum inhibitory concentrations: 1.95-500 µg/mL). Through principal component analysis, characteristic prenylated isoflavones such as 6,8-diprenlygenistein (4) were identified as pivotal compounds that largely determine each part's antibacterial activities. M. tiricuspidata ripe fruits (MTF), which showed the highest antibacterial activity among the parts tested, were optimized for high antibacterial activity and low cytotoxicity on fathead minnow cells using Box-Behnken design. Optimized extraction conditions were deduced to be 50%/80 °C/7.5 h for ethanol concentration/extraction temperature/time, and OE-MTF showed contents of 6,8-diprenlygenistein (4), 2.09% with a MIC of 40 µg/mL. These results suggest that OE-MTF and its active isoflavones have promising potential as eco-friendly antibacterial agents against streptococcosis in aquaculture.
Assuntos
Antibacterianos , Cyprinidae/microbiologia , Doenças dos Peixes , Frutas/química , Isoflavonas , Maclura/química , Extratos Vegetais/química , Streptococcus iniae/crescimento & desenvolvimento , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Doenças dos Peixes/tratamento farmacológico , Doenças dos Peixes/microbiologia , Isoflavonas/química , Isoflavonas/isolamento & purificação , Isoflavonas/farmacologia , PrenilaçãoRESUMO
Orbitides are plant-derived small cyclic peptides with a wide range of biological activities. Phytochemical investigation of the whole plants of Dianthus chinensis was performed with the aim to discover new bioactive orbitides. Five undescribed proline-containing orbitides, dianthiamides A-E (1-5), were isolated from a methanolic extract of Dianthus chinensis. Their structures were elucidated by extensive analysis of 1D and 2D NMR and HRESI-TOF-MS as well as ESI-MS/MS fragmentation data. The absolute configuration of the amino acid residues of compounds 1-5 was determined by Marfey's method. All compounds were tested for their cytotoxic activity, and dianthiamide A (1) exhibited weak activity against A549 cell line with IC50 value of 47.9 µM.
Assuntos
Amidas/química , Dianthus/química , Peptídeos Cíclicos/química , Prolina/química , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Linhagem Celular Tumoral , Humanos , Isomerismo , Espectroscopia de Prótons por Ressonância MagnéticaRESUMO
Epigenome-wide studies of methylation in children support a role for epigenetic mechanisms in asthma; however, studies in adults are rare and few have examined non-atopic asthma. We conducted the largest epigenome-wide association study (EWAS) of blood DNA methylation in adults in relation to non-atopic and atopic asthma.We measured DNA methylation in blood using the Illumina MethylationEPIC array among 2286 participants in a case-control study of current adult asthma nested within a United States agricultural cohort. Atopy was defined by serum specific immunoglobulin E (IgE). Participants were categorised as atopy without asthma (n=185), non-atopic asthma (n=673), atopic asthma (n=271), or a reference group of neither atopy nor asthma (n=1157). Analyses were conducted using logistic regression.No associations were observed with atopy without asthma. Numerous cytosine-phosphate-guanine (CpG) sites were differentially methylated in non-atopic asthma (eight at family-wise error rate (FWER) p<9×10-8, 524 at false discovery rate (FDR) less than 0.05) and implicated 382 novel genes. More CpG sites were identified in atopic asthma (181 at FWER, 1086 at FDR) and implicated 569 novel genes. 104 FDR CpG sites overlapped. 35% of CpG sites in non-atopic asthma and 91% in atopic asthma replicated in studies of whole blood, eosinophils, airway epithelium, or nasal epithelium. Implicated genes were enriched in pathways related to the nervous system or inflammation.We identified numerous, distinct differentially methylated CpG sites in non-atopic and atopic asthma. Many CpG sites from blood replicated in asthma-relevant tissues. These circulating biomarkers reflect risk and sequelae of disease, as well as implicate novel genes associated with non-atopic and atopic asthma.
Assuntos
Asma , Epigenoma , Adulto , Asma/genética , Estudos de Casos e Controles , Criança , Ilhas de CpG , Metilação de DNA , Epigênese Genética , Estudo de Associação Genômica Ampla , Humanos , Pulmão , Estados UnidosRESUMO
BACKGROUND: Ambient air pollution can contribute to the development and exacerbation of COPD. However, the influence of air pollution on objective COPD phenotypes, especially from imaging, is not well studied. We investigated the influence of long-term exposure to air pollution on lung function and quantitative imaging measurements in a Korean cohort of participants with and without COPD diagnosis. METHODS: Study participants (N = 457 including 296 COPD cases) were obtained from the COPD in Dusty Areas (CODA) cohort. Annual average concentrations of particulate matter less than or equal to 10 µm in diameter (PM10) and nitrogen dioxide (NO2) were estimated at the participants' residential addresses using a spatial air pollution prediction model. All the participants underwent volumetric computerized tomography (CT) and spirometry measurements and completed survey questionnaires. We examined the associations of PM10 and NO2 with FVC, FEV1, emphysema index, and wall area percent, using linear regression models adjusting for age, gender, education, smoking, height, weight, and COPD medication. RESULTS: The age of study participants averaged 71.7 years. An interquartile range difference in annual PM10 exposure of 4.4 µg/m3 was associated with 0.13 L lower FVC (95% confidence interval (CI), - 0.22- -0.05, p = 0.003). Emphysema index (mean = 6.36) was higher by 1.13 (95% CI, 0.25-2.02, p = 0.012) and wall area percent (mean = 68.8) was higher by 1.04 (95% CI, 0.27-1.80, p = 0.008). Associations with imaging phenotypes were not observed with NO2. CONCLUSIONS: Long-term exposure to PM10 correlated with both lung function and COPD-relevant imaging phenotypes in a Korean cohort.
Assuntos
Poluição do Ar/efeitos adversos , Exposição Ambiental/efeitos adversos , Dióxido de Nitrogênio/efeitos adversos , Material Particulado/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Poluentes Atmosféricos/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dióxido de Nitrogênio/administração & dosagem , Material Particulado/administração & dosagem , Fenótipo , Doença Pulmonar Obstrutiva Crônica/etiologia , República da Coreia/epidemiologia , Fatores de Tempo , Tomografia Computadorizada por Raios X/tendênciasRESUMO
Actinidia arguta, commonly called hardy kiwifruit or kiwiberry, has cold-resistant properties and can be cultivated in Asia, including Korea. Seven new triterpenoids (2-4 and 8-11) along with eight known triterpenoids were isolated from the leaves of A. arguta through various chromatographic techniques. The new triterpenoids were defined as actiniargupenes A-C (2-4), actinidic acid derivatives with phenylpropanoid constituent units, dehydroisoactinidic acid (8), and actiniargupenes D-F (9-11), asiatic acid derivatives with phenylpropanoid substituents, on the basis of 1D and 2D NMR and MS data. Among the triterpenoids, those with a phenylpropanoid constituent unit showed inhibitory activity on α-glucosidase, which suggested the importance of the phenylpropanoid moiety. Molecular docking analysis demonstrated the interaction between the 4'-OH group of the phenylpropanoid moiety and α-glucosidase.