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Marine natural products play an important role in biopesticides. Seven new secondary metabolites with different structural classes, including two cycloheptapeptides, scortide A (1) and scortide B (2), two 19-nor-diterpenoids, talascortene H (3) and talascortene I (4), two diterpenoid acids, talascortene J (5) and talascortene K (6), and one triterpenoid, talascortene L (7) were isolated and identified from the sea-anemone-derived endozoic fungus Talaromyces scorteus AS-242. Their structures were comprehensively assigned by spectroscopic data analysis, single-crystal X-ray diffraction, tandem mass spectrometry, and electronic circular dichroism (ECD) calculations. The result of the antimicrobial assay demonstrated that compounds 1 - 6 have inhibitory activity against several human, aquatic, and plant pathogens with minimum inhibitory concentration (MIC) values ranging from 1 to 64 µg/mL. Specially, compounds 2 and 4 showed significant activities against the pathogenic fungus Curvularia spicifera with the MIC value of 1 µg/mL, providing an experimental basis of 2 and 4 with the potential as lead compounds to be developed into biopesticides.
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Pruebas de Sensibilidad Microbiana , Talaromyces , Humanos , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Fungicidas Industriales/farmacología , Fungicidas Industriales/química , Fungicidas Industriales/aislamiento & purificación , Estructura Molecular , Relación Estructura-Actividad , Talaromyces/química , Talaromyces/metabolismo , Diterpenos/química , Diterpenos/aislamiento & purificación , Diterpenos/farmacologíaRESUMEN
The radical decarboxylative azidation of structurally diverse uronic acids has been established as an efficient approach to reverse glycosyl azides and rare sugar-derived glycosyl azides under the action of Ag2CO3, 3-pyridinesulfonyl azide, and K2S2O8. The power of this method has been highlighted by the divergent synthesis of 4'-C-azidonucleosides using Vorbrüggen glycosylation of nucleobases with 4-C-azidofuranosyl acetates. The antiviral assessment of the resulting nucleosides revealed one compound as a potential inhibitor of covalently closed circular DNA.
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Antivirales , Azidas , Nucleósidos , Azidas/química , Antivirales/síntesis química , Antivirales/química , Antivirales/farmacología , Estructura Molecular , Nucleósidos/química , Nucleósidos/síntesis química , Nucleósidos/farmacología , GlicosilaciónRESUMEN
The cinnamoyl lipid compound youssoufene A1 (1), featuring a unique dearomatic carbon-bridged dimeric skeleton, exhibits increased inhibition against multidrug resistant Enterococcus faecalis as compared to monomeric youssoufenes. However, the formation process of this intriguing dearomatization/dimerization remains unknown. In this study, an unusual "gene-within-gene" thioesterase (TE) gene ysfF was functionally characterized. The gene was found to naturally encodes two proteins, an entire YsfF with α/ß-hydrolase and 4-hydroxybenzoyl-CoA thioesterase (4-HBT)-like enzyme domains, and a nested YsfFHBT (4-HBT-like enzyme). Using an intracellular tagged carrier-protein tracking (ITCT) strategy, in vitro reconstitution and in vivo experiments, we found that: i) both domains of YsfF displayed thioesterase activities; ii) YsfF/YsfFHBT could accomplish the 6π-electrocyclic ring closure for benzene ring formation; and iii) YsfF and cyclase YsfX together were responsible for the ACP-tethered dearomatization/dimerization process, possibly through an unprecedented Michael-type addition reaction. Moreover, site-directed mutagenesis experiments demonstrated that N301, E483 and H566 of YsfF are critical residues for both the 6π-electrocyclization and dimerization processes. This study enhances our understanding of the multifunctionality of the TE protein family.
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Lípidos , Tioléster Hidrolasas , Dimerización , Tioléster Hidrolasas/química , Mutagénesis Sitio-DirigidaRESUMEN
Silvetia siliquosa, the only species of the family Fucaceae in China, is used as a medicine food homology. Fucoidan from S. siliquosa was extracted by hot water twice thoroughly (13 % of total yield), and a purified fucoidan SSF with a molecular weight of 93 kD was obtained. Chemical composition analysis demonstrated that SSF was primarily composed of sulfate (21.68 wt%) and fucose (84 % of all neutral monosaccharides). IR, methylation analysis, NMR and ESI-MS results indicated SSF had the backbone of mainly (1 â 3)-α-L-fucopyranose and minor (1 â 4)-α-L-fucopyranose, with little 1,3 and 1,4 branched ß-D-Xylp and ß-D-Galp. The in vitro immunomodulatory test on RAW 264.7 cells showed that SSF could up-regulate the expression of immune related factors and proteins in a concentration-dependent manner, but the immunomodulatory effect disappeared from desulfated SSF. This research indicated that highly sulfated fucan possessed immunomodulatory effect and the importance of sulfate groups in the activity of SSF.
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Phaeophyceae , Polisacáridos , Animales , Ratones , Células RAW 264.7 , Polisacáridos/farmacología , Polisacáridos/química , Sulfatos/química , Pared CelularRESUMEN
An efficient protocol has been established for ß-glycosylations with 2-deoxy-2-(2,4-dinitrobenzenesulfonyl)amino (2dDNsNH)-glucopyranosyl/galactopyranosyl selenoglycosides using PhSeCl/AgOTf as an activating system. The reaction features highly ß-selective glycosylation with a wide range of alcohol acceptors that are either sterically hindered or poorly nucleophilic. Thioglycoside- and selenoglycoside-based alcohols prove to be viable nucleophiles, opening up new opportunities for one-pot construction of oligosaccharides. The power of this approach is highlighted by the efficient assembly of tri-, hexa-, and nonasaccharides composed of ß-(1 â 6)-glucosaminosyl residues based on one-pot preparation of a triglucosaminosyl thioglycoside with DNs, phthaloyl, and 2,2,2-trichloroethoxycarbonyl as the protecting groups of amino groups. These glycans are potential antigens for developing glycoconjugate vaccines against microbial infections.
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Oligosacáridos , Tioglicósidos , Glicosilación , Oligosacáridos/químicaRESUMEN
Neuronal apoptosis is considered one of the hallmarks of ischemic stroke. Dual specificity phosphatase 10 (DUSP10), a member of the dual-specificity phosphatase family, which is involved in the regulation of apoptosis process. This study aimed to investigate the effect of on apoptosis in primary cortical neurons exposed to oxygen-glucose deprivation and reoxygenation (OGD/R) and mice suffered from transient middle cerebral artery occlusion and reperfusion (MCAO/R). The results showed that DUSP10 overexpression improved survival and reduced apoptosis in neurons subjected to OGD/R, which was manifested by decreased apoptotic proteins (cleaved caspase 3 and bax) and TUNEL+ cells, as well as increased the anti-apoptotic protein (bcl-2). DUSP10 overexpression inhibited the p38/JNK signaling pathway after OGD/R treatment, whilst DUSP10 knockdown had opposite effects. In addition, the p38 inhibitor SB203580 or JNK inhibitor SP600125 attenuated the increased apoptosis of OGD/R-stimulated neurons treated with DUSP10 silencing. Consistently, DUSP10 knockdown exacerbated infarct volume in MCAO/R injury. The data of Nissl staining and TUNEL-NeuN double staining revealed that DUSP10 interference aggravated neuronal damage in the ischemic penumbra of mice. Furthermore, DUSP10 inhibition activated the p38/JNK axis accompanied by enhanced phosphorylation of p38 and JNK in vivo. In summary, DUSP10 is a neuroprotective agent against ischemic stroke-induced neuronal damage via suppressing the p38/JNK signaling pathway.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Daño por Reperfusión , Animales , Ratones , Apoptosis , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo , Glucosa/metabolismo , Infarto de la Arteria Cerebral Media/metabolismo , Accidente Cerebrovascular Isquémico/metabolismo , Sistema de Señalización de MAP Quinasas , Neuronas/metabolismo , Oxígeno/metabolismo , Daño por Reperfusión/metabolismoRESUMEN
RATIONALE: Thymoma is a rare malignant tumor but it is the most common primary tumor of the anterior mediastinum. The current imaging methods for thymoma screening suffer from false positive rate problems, and thymoma pathogenesis remains elusive. Study of thymoma metabolic characteristics could provide clues for improving the diagnosis and understanding the pathogenesis of thymoma. METHODS: Metabolic profiling of plasma from thymoma and thymic hyperplasia patients was performed using ultrahigh-performance liquid chromatography combined with high-resolution mass spectrometry in both positive and negative ionization modes. After pre- and post-processing, the dataset was divided into three age groups and statistical analysis was performed to select differential metabolites of thymoma. For feature identification, experimental tandem mass spectra were matched to those of databases and available chemical standards, and also manually annotated with plausible chemical structures to ensure high identification confidence. RESULTS: A total of 47 differential metabolites were identified in thymoma. Significantly higher levels of histidine, sphinganine 1-phosphate, lactic acid dimer, phenylacetylglutamine, LPC (18:3) and LPC (16:1), and significantly lower levels of phenylalanine, indole-3-propionic acid (IPA), hippuric acid and mesobilirubinogen were associated with thymoma. Tryptophan level in thymoma-associated myasthenia gravis (TAMG) was significantly lower than that of the MG(-) group. IPA and hippuric acid abundances exhibited increasing trends from indolent to aggressive thymoma. CONCLUSIONS: Our study revealed aberrant aromatic amino acid metabolism and fatty acid oxidation might be associated with thymoma. The identified unique metabolic characteristics of thymoma may provide valuable information for study of the molecular mechanism of thymoma pathogenesis, and improvement of diagnosis and discovery of new therapeutic strategies for thymoma.
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Timoma , Hiperplasia del Timo , Neoplasias del Timo , Humanos , Timoma/complicaciones , Timoma/diagnóstico , Timoma/patología , Hiperplasia del Timo/complicaciones , Hiperplasia del Timo/patología , Neoplasias del Timo/complicaciones , Neoplasias del Timo/diagnóstico , Neoplasias del Timo/patología , Metabolómica , Espectrometría de Masas , Cromatografía LiquidaRESUMEN
Background/Aims: The gastrointestinal symptom of diabetes mellitus, chronic constipation, seriously affects patients' life. Whereas, the mechanism of chronic constipation is still ambiguous, resulting in a lack of effective therapies for this symptom. As a part of the smooth muscle cells, interstitial cells of Cajal, and platelet-derived growth factor receptor alpha-positive (PDGFRα+) cells syncytium (SIP syncytium), PDGFRα+ cells play an important role in regulating colonic motility. According to our previous study, in PDGFRα+ cells in colons of diabetic mice, the function of the P2Y1 purinergic receptor/type 3 small-conductance calcium-activated potassium (SK3) channel signaling pathway is strengthened, which may lead to colonic dysmotility. The purpose of this study is to investigate the changes in SK3 channel properties of PDGFRα+ cells in diabetic mice. Methods: Whole-cell patch clamp, Western blotting, superoxide dismutase activity measurement, and malondialdehyde measurement were main methods in the present study. Results: The present study revealed that when dialysed with low calcium ion (Ca2+) solution, the SK3 current density was significantly decreased in PDGFRα+ cells from diabetic mice. However, the SK3 current density in PDGFRα+ cells was enhanced from diabetic mice when dialysed with high Ca2+ solution. Moreover, hydrogen peroxide-treatment mimicked this phenomenon in SK3 transgenic HEK293 cells. The subunit of SK3 channels, protein kinase CK2, was up-regulated in colonic muscle layers and hydrogen peroxide-treated HEK293 cells. Additionally, protein phosphatase 2A, the subunit of SK3 channels, was not changed in streptozotocin-treated mouse colons or hydrogen peroxide-treated HEK293 cells. Conclusion: The diabetic oxidative stress-induced upregulation of CK2 contributed to modulating SK3 channel sensitivity to Ca2+ in colonic PDGFRα+ cells, which may result in colonic dysmotility in diabetic mice.
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Purpose: This study aimed to investigate the expression of inducible T-cell co-stimulator (ICOS) and its ligand (ICOSLG), along with their association with clinicopathological features and influence on the immune profile in colorectal cancer (CRC). Patients and Methods: The Cancer Genome Atlas Colorectal Adenocarcinoma cohorts were used. We also analyzed 131 clinical samples of colon lesions, including precancerous lesions (hyperplastic polyps, low-grade dysplasia, and high-grade dysplasia) and CRC tissues. We conducted immunohistochemical (IHC) assays and multiple IHC (mIHC) of CD4+, Foxp3+ tumor-infiltrating lymphocytes (TILs), and PD-1/PD-L1 immune checkpoints in precancerous lesions and CRC samples from our patient subsets to determine changes and correlations in ICOS and ICOSLG expression during progression through the adenoma-carcinoma pathway. Results: High expression of ICOS and ICOSLG was a significant factor in CRC in multiple analyses and was positively correlated with CD4+/Foxp3+ TIL density and PD-1/PD-L1 expression, which increased with the sequential progression of lesions from precancerous tissues to carcinoma. Multivariable logistic regression analysis suggested that the location and expression level of ICOS/ICOSLG may be involved in precancerous-carcinoma progression. The co-expression status of PD-1 and ICOS/ ICOSLG could stratify patients with colorectal lesions into three groups of low, moderate, and high risk of progression. According to this classification and mIHC assays, we found a strong correlation between increased PD-1+ICOS+ or PD-1+ICOSLG+ co-expression and CRC, which might be deemed an independent factor in carcinogenesis. Conclusion: Increased ICOS/ICOSLG expression may be associated with the progressive formation of Foxp3+ TILs in the immune microenvironment and may further promote the development of the abnormal cytology of colorectal lesions from precancerous neoplasia to CRC. Our findings support the interpretation that enhanced co-expression of PD-1+ICOS+ or PD-1+ICOSLG+ contributes to the immune-active microenvironment of the colorectal adenoma-carcinoma sequence.
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Background: We quantified and evaluated the allocation of soil and water resources in the Aksu River Basin to measure the consequences of climate change on an agricultural irrigation system. Methods: We first simulated future climate scenarios in the Aksu River Basin by using a statistical downscaling model (SDSM). We then formulated the optimal allocation scheme of agricultural water as a multiobjective optimization problem and obtained the Pareto optimal solution using the multi-objective grey wolf optimizer (MOGWO). Finally, optimal allocations of water and land resources in the basin at different times were obtained using an analytic hierarchy process (AHP). Results: (1) The SDSM is able to simulate future climate change scenarios in the Aksu River Basin. Evapotranspiration (ET0) will increase significantly with variation as will the amount of available water albeit slightly. (2) To alleviate water pressure, the area of cropland should be reduced by 127.5 km2 under RCP4.5 and 377.2 km2 under RCP8.5 scenarios. (3) To be sustainable, the allocation ratio of forest land and water body should increase to 39% of the total water resource in the Aksu River Basin by 2050.
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Cambio Climático , Agua , Agricultura , Riego Agrícola , ChinaRESUMEN
An efficient approach to 6-deoxy-heptose constructs has been established by one-carbon homologation of the sugar chain of hexoses. The reaction features the formation of sugar-based α-substituted propanedinitriles and ensuing diverse oxidative transformations under mild reaction conditions that are compatible with a wide range of sugars bearing various functional/protecting groups. The applications of this method are demonstrated by a divergent assembly of Campylobacter jejuni strain 81-176 capsular trisaccharide repeating unit derivatives.
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Campylobacter jejuni , Trisacáridos , Carbono , Heptosas , HexosasRESUMEN
Gold(I)-catalyzed stereoselective ß-glycosylation of primary alcohols is achieved using the orthogonally protected mannosyl α-ortho-hexynylbenzoate (OABz) donors devoid of 4,6-O-tethering groups used in conventionally constructing ß-mannosidic bonds. The potential of this methodology is showcased by the first assembly of ß-1,6-tri/hexa-/nonamannosides and related sulfated congeners through a convergent strategy. The synthesis features the stereocontrolled ß-glycosylation of α-trimannosyl OABz donors and the late-stage sulfonation. This work is expected to expedite the preparation of ß-1,6-mannans and functionalized derivatives.
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Our previous study indicated that streptozotocin (STZ)-induced diabetes leads to colonic platelet-derived growth factor receptor-α-positive (PDGFRα+ ) cell proliferation accompanied by slow colonic transit in mice; however, the mechanism of this effect is unclear. The present study used western blotting, immunohistochemistry, and quantitative PCR to investigate whether proteinase-activated receptor 2 (PAR2) mediates PDGFRα+ cell proliferation. Our results showed that PDGFRα, PAR2, and Ki-67 coexpression was increased in the diabetic colonic muscle layer. PDGFRα and PAR2 mRNA and protein expression levels were also markedly enhanced in the diabetic colonic muscle layer. Mice treated with 2-furoyl-LIGRLO-amide (2-F-L-a), a PAR2 agonist, exhibited significant colon elongation and increased smooth muscle weight. In the 2-F-L-a-treated mice, PDGFRα, PAR2, and Ki-67 coexpression was increased and PDGFRα and PAR2 mRNA and protein expression was significantly enhanced in the colonic smooth muscle layer. 2-F-L-a also increased proliferation and PDGFRα expression in NIH/3T3 cells cultured in high glucose, while LY294002, a PI3K antagonist, decreased cell proliferation and PDGFRα expression. PI3K and Akt protein and mRNA expression and p-Akt protein expression in diabetic and 2-F-L-a-treated mice were markedly reduced in colonic smooth muscle. 2-F-L-a also reduced PI3K, Akt, and p-Akt protein expression in NIH/3T3 cells, while the PI3K antagonist LY294002 increased this expression. The results indicate that PAR2 is involved in the proliferation of PDGFRα+ cells through the PI3K/Akt signaling pathway in the colon of STZ-induced diabetic mice, which may contribute to the slow transit and constipation that are associated with diabetes.
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Proliferación Celular , Colon/metabolismo , Diabetes Mellitus Experimental/metabolismo , Receptor PAR-2/metabolismo , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Animales , Células Cultivadas , Colon/citología , Colon/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos ICR , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/fisiología , Células 3T3 NIH , Oligopéptidos/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptor PAR-2/agonistas , Receptor PAR-2/genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Transducción de SeñalRESUMEN
Human milk oligosaccharides (HMOs) exhibit various biological activities for infants, such as serving as prebiotics, blocking pathogens, and aiding in brain development. HMOs are a complex mixture of hetero-oligosaccharides that are generally highly branched, containing multiple structural isomers and no intrinsic chromophores, presenting a challenge to both their resolution and quantitative detection. While liquid chromatography-mass spectrometry (LC-MS) has become the primary strategy for analysis of various compounds, the very polar and chromophore-free properties of native glycans hinder their separation in LC and ionization in MS. Various labeling approaches have been developed to achieve separation of glycans with higher resolution and greater sensitivity of detection. Here, we compared five commonly used labeling techniques [by 2-aminobenzamide, 2-aminopyridine, 2-aminobenzoic acid (2-AA), 2,6-diaminopyridine, and 1-phenyl-3-methyl-5-pyrazolone] for analyzing HMOs specifically under hydrophilic-interaction chromatography-mass spectrometry (HILIC-MS) conditions. The 2-AA labeling showed the most consistent deprotonated molecular ions, the enhanced sensitivity with the least structural selectivity, and the sequencing-informative tandem MS fragmentation spectra for the widest range of HMOs; therefore, this labeling technique was selected for further optimization under the porous graphitized carbon chromatography-mass spectrometry (PGC-MS) conditions. The combination strategy of 2-AA labeling and PGC-MS techniques provided online decontamination (removal of excess 2-AA, salts, and lactose) and resolute detection of many HMOs, enabling us to characterize the profiles of complicated HMO mixtures comprehensively in a simple protocol.
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Objective: To investigate the effects of IMPX977 on long term potentiation (LTP) at Schaffer collateral-CA1 synapses in vitro and on methyl CpG binding protein 2 (Mecp2) expression in mice cortex and hippocampus. Methods: Thirty-two C57BL/6 mice were randomly divided into four groups: control, olive oil (vehicle), IMPX977 low (5 mg/kg) and high (15 mg/kg) groups. Mice were administrated every other day orally for two weeks. Extracellular recording technique in vitro was used to record the effects of IMPX977 on Schaffer collateral-CA1 LTP pathway in acute mice hippocampal slices. The Mecp2 protein expression level was detected by Western blotting. Results: Compared to the control group, vehicle did not alter the synaptic transmission in Schaffer collateral-CA1 synapses, however, IMPX977 at concentrations of 5 mg/kg and 15 mg/kg significantly enhanced fEPSP (field excitatory postsynaptic potential) slope in Schaffer collateral-CA1 pathway to (179.6 ± 17.8)% and (191.4 ± 21.4)%, individually 60 min after HFS, IMPX977 improved LTP induction significantly at Schaffer collateral-CA1 pathway at least. Also, IMPX977 significantly elevated MeCP2 protein level in cortex. Conclusion: The effects of IMPX977 on synaptic transmission and Mecp2 protein expression provided convincing evidence that IMPX977 could be promising new drug candidates for Rett syndrome treatment.
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It is generally considered that enteric neuropathy is one of the causative factors in diabetic gastroparesis. Our previous study demonstrated that there is a loss of NOS neurons in diabetic mice. However, the underlying mechanism remains unclear. The present study was designed to clarify the relationship between neuronal P2X7R and NOS neuron damage. The effect of P2X7R on diabetes-induced gastric NOS neurons damage and its mechanism were investigated by using quantitative RT-PCRï¼immunofluorescence, western blot, isometric force recording, intracellular calcium ([Ca2+]i) measurement and whole-cell patch clamp techniques. The immunohistochemistry and western blot results showed that nNOS expression was significantly down-regulated in diabetic mice, meanwhile, electric field stimulation-induced NOS sensitive relaxation was significantly suppressed. Myenteric neurons expressed P2X7R and pannexin1, and the mRNA and protein level of P2X7R and pannexin1 were up-regulated in diabetic mice. BzATP, a P2X7R activator, evoked [Ca2+]i increase in Hek293 cells with heterologous expression of P2X7R (Hek293-P2X7R cells) and the same dose of ATP-induced [Ca2+]i was more obvious in Hek293-P2X7R cells than in Hek293 cells. Application of BzATP activated an inward current of Hek293-P2X7R in a dose dependent manner. Hek293-P2X7R but not untransfected Hek293 cells could take up of YO-PRO-1. In addition, the uptake of YO-PRO-1 by Hek293-P2X7R was blocked by oxATP, a P2X7 antagonist and CBX, a pannexin1 inhibitor. The results suggest that the P2X7R of enteric neurons may be involved in diabetes-induced NOS neuron damage via combining with pannexin-1 to form transmembrane pores which induce macromolecular substances and calcium into the cells.
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Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Mucosa Gástrica/metabolismo , Neuronas/metabolismo , Óxido Nítrico/metabolismo , Receptores Purinérgicos P2X7/metabolismo , Adenosina Trifosfato/análogos & derivados , Adenosina Trifosfato/farmacología , Animales , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Calcio/metabolismo , Fundus Gástrico/efectos de los fármacos , Fundus Gástrico/metabolismo , Mucosa Gástrica/efectos de los fármacos , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Células HEK293 , Humanos , Espacio Intracelular/efectos de los fármacos , Espacio Intracelular/metabolismo , Masculino , Ratones , Ratones Endogámicos ICR , Neuronas/efectos de los fármacos , Neuronas/patología , Óxido Nítrico Sintasa de Tipo I/metabolismoRESUMEN
BACKGROUND: In this study, we evaluated the effect of rs6265 polymorphism on the expression of brain-derived neurotrophic factor (BDNF) and relevant downstream targets, as well as the involvement of this polymorphism in bladder cancer. METHOD: A computational analysis and luciferase assays were used to explore the interaction among BDNF, miR-205, and cyclin J (CCNJ). Real-time polymerase chain reaction (RT-PCR) and Western blot analysis were carried out to determine the effect of rs6265 polymorphism on the expression of BDNF and relevant downstream genes. RESULT: BDNF directly inhibited miR-205 expression but enhanced the expression of CCNJ, which was identified as a virtual target gene of miR-205. Furthermore, the inhibitory effect of BDNF carrying the Val genotype, defined as BDNF (Val), on miR-205 expression was much stronger than that of BDNF (Met), while the inductive effect of BDNF (Val) on CCNJ expression was much weaker than that of BDNF (Met). miR-205 and CCNJ small interfering RNA (siRNA) were found to reduce cell proliferation and arrest the cells in G0/G1 phase. In addition, miR-205 expression in patients carrying BDNF genotyped as Met/Met (defined as Met/Met group) was much higher than patients carrying BDNF genotyped as Val/Val and Val/Met (defined as Val/Val group and Val/Met group). As an inhibitor of CCNJ expression, the inhibitory effect of miR-205 was much higher in the Met/Met group than that in the Val/Val and Val/Met groups. CONCLUSION: In summary, we suggested that the rs6265 polymorphism in BDNF upregulates the expression of CCNJ in bladder cancer via the inhibition of miR-205 expression, which leads to the promoted proliferation of bladder cancer cells.
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The DSSAT model, integrated the calibrated Hargreaves ET model and dynamic crop coefficient, was run with the generated weather data by SDSM4.2 and CanESM2 to predict the potential yield and crop water requirement (ETC) of winter wheat in the Huang-Huai-Hai Plain in China under RCP4.5 and RCP8.5 scenarios. The results showed that the spatial distribution of potential yield in the future under RCP4.5 and RCP8.5 were similar, characterized by an increasing trend from the northwest inland to the southeast coast. The spatial distribution of ETC decreased gradually from the Shandong Peninsula to the surrounding area, and the minimum ETC was observed in the southern part of Huang-Huai-Hai Plain. The potential yield, ETC, and effective precipitation during winter wheat growing seasons might increase in the future under RCP4.5, while irrigation water requirements (IWR) would decrease. Under RCP8.5, the effective precipitation during the wheat growing seasons decreased first and then increased. However, the potential yield, ETC, and IWR of winter wheat increased first and then decreased. This study can provide some scientific evidence to mitigate the negative effects of climate change on agricultural production and water use in the Huang-Huai-Hai Plain.
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Riego Agrícola , Cambio Climático , Modelos Teóricos , Estaciones del Año , Triticum/fisiología , Aclimatación , China , Transpiración de PlantasRESUMEN
BACKGROUND/AIMS: Genistein is a natural isoflavone enriched in soybeans. It has beneficial effects for patients with mucopolysaccharidose type III through inhibiting glycosaminoglycan biosynthesis. However, other studies indicate that genistein does not always inhibit glycosaminoglycan biosynthesis. METHODS: To understand the underlying molecular mechanisms, CHOK1, CHO3.1, CHO3.3, and HCT116 cells were treated with genistein and the monosaccharide compositions and quantity of all glycans from the cell lysate were measured after thorough acid hydrolysis followed by HPLC analysis. In addition, the glycosaminoglycan disaccharide compositions were obtained by stable isotope labeling coupled with LC/MS analysis. RESULTS: Genistein treatment reduced the amount of glycans but increased the amount of glycosaminoglycans in HCT116 cells. In contrast, genistein treatment reduced both glycan and glycosaminoglycan quantities in CHOK1, CHO3.1, and CHO3.3 cells in addition to differential changes in glycosaminoglycan disaccharide compositions. CONCLUSION: Genistein treatment reduced overall glycan quantity but glycosaminoglycan quantities were either increased or decreased in a cell type-dependent manner.