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1.
Trends Biotechnol ; 38(5): 468-469, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32302578

RESUMO

Microbial production of medium-chain fatty acids (MCFAs) is challenging, as they are rare metabolites and toxic to cells. Recently, Zhu et al. performed multidimensional engineering in Saccharomyces cerevisiae, including engineering fatty acid synthases and improving cellular tolerance to MCFAs, to build an efficient MCFA cell factory.

2.
J Integr Med ; 18(3): 229-241, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32307268

RESUMO

OBJECTIVE: Lung-toxin Dispelling Formula No. 1, referred to as Respiratory Detox Shot (RDS), was developed based on a classical prescription of traditional Chinese medicine (TCM) and the theoretical understanding of herbal properties within TCM. Therapeutic benefits of using RDS for both disease control and prevention, in the effort to contain the coronavirus disease 2019 (COVID-19), have been shown. However, the biochemically active constituents of RDS and their mechanisms of action are still unclear. The goal of the present study is to clarify the material foundation and action mechanism of RDS. METHODS: To conduct an analysis of RDS, an integrative analytical platform was constructed, including target prediction, protein-protein interaction (PPI) network, and cluster analysis; further, the hub genes involved in the disease-related pathways were identified, and the their corresponding compounds were used for in vitro validation of molecular docking predictions. The presence of these validated compounds was also measured in samples of the RDS formula to quantify the abundance of the biochemically active constituents. In our network pharmacological study, a total of 26 bioinformatic programs and databases were used, and six networks, covering the entire Zang-fu viscera, were constructed to comprehensively analyze the intricate connections among the compounds-targets-disease pathways-meridians of RDS. RESULTS: For all 1071 known chemical constituents of the nine ingredients in RDS, identified from established TCM databases, 157 passed drug-likeness screening and led to 339 predicted targets in the constituent-target network. Forty-two hub genes with core regulatory effects were extracted from the PPI network, and 134 compounds and 29 crucial disease pathways were implicated in the target-constituent-disease network. Twelve disease pathways attributed to the Lung-Large Intestine meridians, with six and five attributed to the Kidney-Urinary Bladder and Stomach-Spleen meridians, respectively. One-hundred and eighteen candidate constituents showed a high binding affinity with SARS-coronavirus-2 3-chymotrypsin-like protease (3CLpro), as indicated by molecular docking using computational pattern recognition. The in vitro activity of 22 chemical constituents of RDS was validated using the 3CLpro inhibition assay. Finally, using liquid chromatography mass spectrometry in data-independent analysis mode, the presence of seven out of these 22 constituents was confirmed and validated in an aqueous decoction of RDS, using reference standards in both non-targeted and targeted approaches. CONCLUSION: RDS acts primarily in the Lung-Large Intestine, Kidney-Urinary Bladder and Stomach-Spleen meridians, with other Zang-fu viscera strategically covered by all nine ingredients. In the context of TCM meridian theory, the multiple components and targets of RDS contribute to RDS's dual effects of health-strengthening and pathogen-eliminating. This results in general therapeutic effects for early COVID-19 control and prevention.


Assuntos
Antivirais/química , Betacoronavirus/química , Infecções por Coronavirus/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Pneumonia Viral/tratamento farmacológico , Antivirais/uso terapêutico , Betacoronavirus/enzimologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Cisteína Endopeptidases/química , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Espectrometria de Massas , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/virologia , Mapas de Interação de Proteínas , Proteínas não Estruturais Virais/química
3.
Inorg Chem ; 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32275143

RESUMO

Macrocyclic molecules with multiple coordination sites have been widely used as promising ligands to build polynuclear metal clusters; however, cyclic silsesquioxane-based metal clusters are still rare. Herein, we report a new octanuclear Co-silsesquioxane cluster [Co8(OH)2{(MeSiO2)6}2(bpy)2(Obpy)2] (SD/Co8c; SD = SunDi), wherein the Co8 disc-like core is sandwiched by two hexamethylcyclohexasiloxanolate ligands (MeSiO2)6 at two poles and finally encircled by two bpy (bpy = 2,2'-bipyridine) and two Obpy (HObpy = 6-hydroxy-2,2'-bipyridine) ligands at the equatorial region. Interestingly, both MeSi(OMe)3 and bpy undergo in situ transformations to generate hexameric cyclic (MeSiO2)6 and Obpy, respectively. The unusual hydroxylation of bpy and the OH- anion in the center of Co8 core provide additional binding sites to induce the formation of the larger cluster instead of the traditional hexanuclear cluster. The solution stability and fragmentation route in the gas phase were studied by cold-spray ionization and collision-induced dissociation mass spectrometry, respectively. Both results reveal that the Co8 core is quite stable in solution as well as in the gas phase, even with increased collision voltage. Magnetic susceptibility studies of SD/Co8c show the slow magnetization relaxation indicative of single-molecule magnet (SMM) behavior. This work not only presents the multiple in situ ligand-transformation-assisted assembly of polynuclear cobalt cluster but also provides some new insights into the magnetism-structure relationship for SMMs.

4.
Zhongguo Zhong Yao Za Zhi ; 45(2): 267-273, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32237308

RESUMO

In this study, the texture analyzer acupuncture pressure sensor was used to objectively characterize the "herb soaking with exact amount of water" for moistening process of ginseng. The single factor rotation experiment was used to investigate the effects of puncture speed, puncture depth and puncture site on puncture force and work. According to ginseng processing method in Chinese Pharmacopoeia, ginseng medicinal materials with diameters of about 1 cm and 2 cm were selected, and puncture experiments were carried out at the set measurement time to determine the hardness, work and water absorption of the ginseng moistening process. The endpoint threshold for the ginseng softening process was determined and verified. To reflect the actual internal conditions of the ginseng softening process, the puncture depth was preferably 70%, and the puncture speed was 30 mm·min~(-1). In the ginseng moistening process, the softening hardness and the puncture work were in accordance with the first-order kinetic equation y=a×exp(-k×x). The 0 h initial hardness a of 1 cm and 2 cm ginseng herbs were 289.8 N and 1 227 N, and the rate constants K were 0.149 4 N·h~(-1) and 0.100 7 N·h~(-1), respectively. After the ginseng was completely softened, the force required for puncture was 10 N, which can be used as the standard for "drug penetration". At this time, the water absorption rate of ginseng was 70%-100%. The softening time of ginseng with a diameter of 1 cm was about 20-22 h, and the softening time of ginseng with a diameter of 2 cm was about 40-46 h. A needle-type pressure sensor was used to accurately determine the end point of the softening process of ginseng and reduce the loss of active ingredients. The study results provide reference for the softening process kinetics and the process intelligent monitoring of other dried roots and rhizomes.

6.
J Nat Prod ; 83(4): 1082-1091, 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-32130008

RESUMO

Fumiquinazoline alkaloids have attracted much attention from medicinal and natural product chemists due to their interesting structures and biological potential. In this study, three new and 12 known fumiquinazoline alkaloids were isolated and characterized from the marine fungus Scedosporium apiospermum F41-1. The structures of the new compounds and their absolute configurations were determined using NMR spectroscopy, ECD, and OR calculations. The compounds were evaluated for their antidiabetic potential by determining their triglyceride-promoting activity using 3T3-L1 adipocytes. One of the new compounds, scequinadoline J (14), as well as scequinadolines D (9) and E (10), was found to promote triglyceride accumulation in 3T3-L1 cells. Scequinadoline D (9) demonstrated the most potent activity, with an EC50 value of 0.27 ± 0.03 µM. Quantitative polymerase chain reaction experiments suggested that scequinadoline D (9) acts through activation of the PPARγ pathway. It stimulated the mRNA expression of PPARγ, AMPKα, C/EBPα, LXRα, SCD-1, and FABP4. In addition, its triglyceride-promoting efficacy could be blocked by a double dose of the PPARγ antagonist GW9662. These results indicated that scequinadoline D (9) is a potent insulin sensitizer that targets adipocytes and may be useful for the treatment of type 2 diabetes mellitus after further investigation.

7.
Mar Drugs ; 18(2)2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32028626

RESUMO

Three new compounds, monarubins A-C (1, 6 and 13), together with ten known compounds, including four alkaloids (2-5), two isocoumarins (7 and 8) and four polyketides (9-12), were isolated from marine shellfish-associated fungus Monascus ruber BB5. The structures were determined on the basis of the 1D and 2D NMR, MS, UV and IR data. The absolute configurations of compounds 3, 6 and 13 were determined by ECD calculations. The NMR data of compounds deoxyhydroxyaspergillic acid (3) and 2-hydroxy-6-(1-hydroxy-1-methylpropyl)-3-sec-buthylpyrazine (4) were first reported. All of the isolated compounds were evaluated for their cytotoxic activities against human nasopharyngeal carcinoma cell lines CNE1, CNE2, SUNE1 and HONE1 and hepatocellular carcinoma cell lines QGY7701 and HepG2. Monarubin B (6) displayed potent cytotoxicities against the cancer cell lines HepG2 and QGY7701 with IC50 values of 1.72 and 0.71 µΜ, respectively; lunatinin (7) showed moderate cytotoxic activities against the cancer cell lines HepG2, QGY7701 and SUNE1 with the IC50 values of 9.60, 7.12 and 28.12 µΜ, respectively.

8.
Metab Eng ; 59: 36-43, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31954846

RESUMO

Riboswitches with desired properties, such as sensitivity, threshold, dynamic range, is important for its application. However, the property change of a natural riboswitch is difficult due to the lack of the understanding of aptamer ligand binding properties and a proper screening method for both rational and irrational design. In this study, an effective method to change the threshold of riboswitch was established in vivo based on growth coupled screening by combining both positive and negative selections. The feasibility of the method was verified by the model library. Using this method, an N-acetylneuraminic acid (NeuAc) riboswitch was evolved and modified riboswitches with high threshold and large dynamic range were obtained. Then, using a new NeuAc riboswitch, both ribosome binding sites and key gene in NeuAc biosynthesis pathway were optimized. The highest NeuAc production of 14.32 g/l that has been reported using glucose as sole carbon source was obtained.

9.
Auris Nasus Larynx ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31932074

RESUMO

OBJECTIVE: MiR-506 has been reported to be associated with multiple malignancies, but its roles in nasopharyngeal cancer (NPC) are not fully understood. Our objective is to demonstrate its effects on NPC and the underlying mechanisms. METHODS: Totally fifteen pairs of NPC and adjacent non-tumorous tissues were collected for the detection of miR-506 and enhancer of zeste homolog 2 (EZH2) expression. Dual luciferase reporter assay was employed for verifying the relationship between miR-506 and EZH2. The flow cytometry and MTT assays were employed to explore the effects of miR-506 and EZH2 on the cell apoptosis and proliferation, respectively. Wound closure and transwell assays were used to evaluate the cell migration and invasion abilities. Western blotting or RT-qPCR assays were applied to detect the alterations of miR-506, EZH2 and epithelial-mesenchymal transition (EMT)-related markers. Morphological changes of cells with EMT were assessed by light microscopy. RESULTS: MiR-506 was significantly decreased and EZH2 was obviously increased in NPC tissues. Overexpression of miR-506 decreased the EZH2 level, promoted apoptosis, inhibited proliferation, invasion and migration of NPC cells. Accordingly, miR-506 overexpression attenuated EMT process of NPC cells as demonstrated by the alterations of EMT-related markers and the morphological changes. In addition, the luciferase assay proved that miR-506 directly targeted EZH2. Furthermore, the overexpression of EZH2 reversed the tumor-suppressive effects induced by miR-506 mimics. CONCLUSION: MiR-506 acted as a tumor suppressor to promote apoptosis and inhibit invasion and migration via directly targeting EZH2. MiR-506 can be a candidate target for gene therapy against NPC.

10.
Clin Gastroenterol Hepatol ; 18(2): 457-467.e21, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31306800

RESUMO

BACKGROUND & AIMS: Treatment of chronic hepatitis B virus (HBV) infection with entecavir suppresses virus replication and reduces disease progression, but could require life-long therapy. To investigate clinical outcome events and safety associated with long-term treatment with entecavir, we followed up patients treated with entecavir or another standard-of-care HBV nucleos(t)ide analogue for up to 10 years. We assessed long-term outcomes and relationships with virologic response. METHODS: Patients with chronic HBV infection at 299 centers in Asia, Europe, and North and South America were assigned randomly to groups that received entecavir (n = 6216) or an investigator-selected nonentecavir HBV nucleos(t)ide analogue (n = 6162). Study participants were followed up for up to 10 years in hospital-based or community clinics. Key end points were time to adjudicated clinical outcome events and serious adverse events. In a substudy, we examined relationships between these events and virologic response. RESULTS: There were no significant differences between groups in time to event assessments for primary end points including malignant neoplasms, liver-related HBV disease progression, and death. There were no differences between groups in the secondary end points of nonhepatocellular carcinoma malignant neoplasms and hepatocellular carcinoma. In a substudy of 5305 patients in China, virologic response, regardless of treatment group, was associated with a reduced risk of liver-related HBV disease progression (hazard ratio, 0.09; 95% CI, 0.038-0.221) and hepatocellular carcinoma (hazard ratio, 0.03; 95% CI, 0.009-0.113). Twelve patients given entecavir (0.2%) and 50 patients given nonentecavir drugs (0.8%) reported treatment-related serious adverse events. CONCLUSIONS: In a randomized controlled trial of patients with chronic HBV infection, we associated entecavir therapy with a low rate of adverse events over 10 years of follow-up evaluation. Patients receiving entecavir vs another nucleos(t)ide analogue had comparable rates of liver- and non-liver-related clinical outcome events. Participants in a China cohort who maintained a virologic response, regardless of treatment group, had a reduced risk of HBV-related outcome events including hepatocellular carcinoma. ClinicalTrials.gov identifier no: NCT00388674.

11.
Int J Biol Macromol ; 144: 995-1003, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31669470

RESUMO

This paper introduces a cheap simple MWCNTs@paper biosensor for the detection of CA19-9, which is a biomarker of pancreatic cancer. By adding the CA19-9 antibody to the surface of MWCNTs which are deposited on the microporous filter paper, the correlation between the concentration of CA19-9 and resistance of biosensor element was linear due to the site-specific binding of antigen and antibody. The detection range is wide (0 U/mL-at least 1000 U/mL), and even in the low concentration of CA19-9, the linearity remains satisfying. Based on this property, it could be used for the detection of early-stage pancreatic cancer. Besides, this research originally introduces a vacuum freeze-drying method for the long-term preservation of biosensor, prolonging its storage time from 3 h to at least 7 days, which signifcantly promoted its value in practical application. One piece of the MWCNTs@paper biosensor only cost $2 (about 30 times cheaper than ELISA) approximately, and the detection speed is satisfying (2 h, 12 times faster than ELISA), which will possibly increase its opportunity of mass production and clinical practice.

12.
J Nat Prod ; 83(1): 79-87, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31886665

RESUMO

The effects of a single-amino-acid culture strategy on secondary metabolite production in the marine-derived fungus Trichoderma erinaceum F1-1 were investigated by culturing the fungus in GPY medium supplemented or not supplemented with l-phenylalanine. A suite of secondary metabolites, including seven terpenoids (1-7) and one polyketide (8), among which are four new compounds, harziandione A (1), cyclonerodiols A and B (3, 4), and trichodermaerin A (6), were isolated from the GPY medium without l-phenylanine, whereas 18 aromatic compounds (9-26), including six new compounds, trichoderolides A-F (9, 10, and 14-17), were isolated from the culture grown in the GPY medium with l-phenylalanine. The structures of the new compounds were determined by high-resolution mass spectrometry, NMR spectroscopic analysis, optical rotation calculations, chemical methods, and X-ray crystallography. Compounds 10, 12, 13, and 26 exhibited cytotoxic activities against MDA-MB-435 human melanocyte cancer cells. Compound 26 was cytotoxic to A549 adenocarcinomic human alveolar basal epithelial cells.

13.
J Pharm Biomed Anal ; 177: 112813, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31472326

RESUMO

Differentiated composition in precursor ions for different subclasses of ginsenosides in the negative electrospray-ionization mode has been reported, which lays a foundation for the sorted and untargeted identification of ginsenosides. Carboxyl-free ginsenosides simultaneously from Panax ginseng, P. quinquefolius, and P. notoginseng, were comprehensively characterized and statistically compared. A neutral loss/product ion scan (NL-PIS) incorporated untargeted profiling approach, coupled to ultra-high performance liquid chromatography, was developed on a linear ion-trap/Orbitrap mass spectrometer for characterizing carboxyl-free ginsenosides. It incorporated in-source fragmentation (ISF) full scan-MS1, mass tag-MS2, and product ion scan-MS3. Sixty batches of ginseng samples were analyzed by metabolomics workflows for the discovery of ginsenoside markers. Using formic acid (FA) as the additive, carboxyl-free ginsenosides (protopanaxadiol-type, protopanaxatriol-type, and octillol-type) gave predominant FA-adducts, while rich deprotonated molecules were observed for carboxyl-containing ginsenosides (oleanolic acid-type and malonylated) when source-induced dissociation (SID) was set at 0 V. Based on the NL transition [M+FA‒H]- > [M-H]- and the characteristic sapogenin product ions, a NL-PIS approach was established. It took advantage of the efficient full-information acquisition of ISF-MS1 (SID: 50 V), the high specificity of mass tag (NL: 46.0055 Da)-induced MS2 fragmentation, and the substructure fragmentation of product ion scan-MS3. We could characterize 216 carboxyl-free ginsenosides, and 21 thereof were potentially diagnostic for the species differentiation. Conclusively, sorted and untargeted characterization of the carboxyl-free ginsenosides was achieved by the established NL-PIS approach. In contrast to the conventional NL or PIS-based survey scan strategies, the high-accuracy MSn data obtained can enable more reliable identification of ginsenosides.


Assuntos
Ginsenosídeos/análise , Espectrometria de Massas/métodos , Panax/química , Cromatografia Líquida de Alta Pressão/métodos , Íons/análise , Panax/classificação
14.
FEMS Yeast Res ; 19(8)2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31778177

RESUMO

Engineering microbial cell factories is a potential approach of sustainable production of chemicals, fuels and pharmaceuticals. However, testing the production of molecules in high throughput is still a time-consuming and laborious process since product synthesis usually does not confer a clear phenotype. Therefore, it is necessary to develop new techniques for fast high-producer screening. Genetically encoded biosensors are considered to be promising devices for high-throughput analysis owing to their ability to sense metabolites and couple detection to an actuator, thereby facilitating the rapid detection of small molecules at single-cell level. Here, we review recent advances in the design and engineering of biosensors in Saccharomyces cerevisiae, and their applications in metabolic engineering. Three types of biosensor are introduced in this review: transcription factor based, RNA-based and enzyme-coupled biosensors. The studies to improve the features of biosensors are also described. Moreover, we summarized their metabolic engineering applications in dynamic regulation and high producer selection. Current challenges in biosensor design and future perspectives on sensor applications are also discussed.

15.
BMC Med ; 17(1): 204, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31727112

RESUMO

BACKGROUND: Brain innate immunity is vital for maintaining normal brain functions. Immune homeostatic imbalances play pivotal roles in the pathogenesis of neurological diseases including Parkinson's disease (PD). However, the molecular and cellular mechanisms underlying the regulation of brain innate immunity and their significance in PD pathogenesis are still largely unknown. METHODS: Cre-inducible diphtheria toxin receptor (iDTR) and diphtheria toxin-mediated cell ablation was performed to investigate the impact of neuron-glial antigen 2 (NG2) glia on the brain innate immunity. RNA sequencing analysis was carried out to identify differentially expressed genes in mouse brain with ablated NG2 glia and lipopolysaccharide (LPS) challenge. Neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice were used to evaluate neuroinflammatory response in the presence or absence of NG2 glia. The survival of dopaminergic neurons or glial cell activation was evaluated by immunohistochemistry. Co-cultures of NG2 glia and microglia were used to examine the influence of NG2 glia to microglial activation. RESULTS: We show that NG2 glia are required for the maintenance of immune homeostasis in the brain via transforming growth factor-ß2 (TGF-ß2)-TGF-ß type II receptor (TGFBR2)-CX3C chemokine receptor 1 (CX3CR1) signaling, which suppresses the activation of microglia. We demonstrate that mice with ablated NG2 glia display a profound downregulation of the expression of microglia-specific signature genes and remarkable inflammatory response in the brain following exposure to endotoxin lipopolysaccharides. Gain- or loss-of-function studies show that NG2 glia-derived TGF-ß2 and its receptor TGFBR2 in microglia are key regulators of the CX3CR1-modulated immune response. Furthermore, deficiency of NG2 glia contributes to neuroinflammation and nigral dopaminergic neuron loss in MPTP-induced mouse PD model. CONCLUSIONS: These findings suggest that NG2 glia play a critical role in modulation of neuroinflammation and provide a compelling rationale for the development of new therapeutics for neurological disorders.

16.
Chin Med J (Engl) ; 132(19): 2315-2324, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31567376

RESUMO

BACKGROUND: Nucleos(t)ide analog (NA) in combination with peginterferon (PegIFN) therapy in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) shows better effectiveness than NA monotherapy in hepatitis B surface antigen loss, termed "functional cure," based on previous published studies. However, it is not known which strategy is more cost-effective on functional cure. The aim of this study was to analyze the cost-effectiveness of first-line monotherapies and combination strategies in HBeAg-positive CHB patients in China from a social perspective. METHODS: A Markov model was developed with functional cure and other five states including CHB, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and death to assess the cost-effectiveness of seven representative treatment strategies. Entecavir (ETV) monotherapy and tenofovir disoproxil fumarate (TDF) monotherapy served as comparators, respectively. RESULTS: In the two base-case analysis, compared with ETV, ETV generated the highest costs with $44,210 and the highest quality-adjusted life-years (QALYs) with 16.78 years. Compared with TDF, treating CHB patients with ETV and NA - PegIFN strategies increased costs by $7639 and $6129, respectively, gaining incremental QALYs by 2.20 years and 1.66 years, respectively. The incremental cost-effectiveness ratios were $3472/QALY and $3692/QALY, respectively, which were less than one-time gross domestic product per capita. One-way sensitivity analysis and probabilistic sensitivity analyses showed the robustness of the results. CONCLUSION: Among seven treatment strategies, first-line NA monotherapy may be more cost-effective than combination strategies in HBeAg-positive CHB patients in China.

17.
Antioxidants (Basel) ; 8(9)2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31480577

RESUMO

BACKGROUND: Although kidney injury caused by cisplatin has attracted much attention, cisplatin-induced cardiotoxicity is elusive. Our previous studies have confirmed that saponins (ginsenosides) from Panax quinquefolius can effectively reduce acute renal injuries. Our current study aimed to identify the potential effects of saponins from leaves of P. quinquefolius (PQS) on cisplatin-evoked cardiotoxicity. METHODS: Mice were intragastrically with PQS at the doses of 125 and 250 mg/kg daily for 15 days. The mice in cisplatin group and PQS + cisplatin groups received four times intraperitoneal injections of cisplatin (3 mg/kg) two days at a time from the 7th day, respectively. All mice were killed at 48 h following final cisplatin injection. Body weights, blood and organic samples were collected immediately. RESULTS: Our results showed that cisplatin-challenged mice experienced a remarkable cardiac damage with obvious histopathological changes and elevation of lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB) and cardiac troponin T (cTnT) concentrations and viabilities in serum. Cisplatin also impaired antioxidative defense system in heart tissues manifested by a remarkable reduction in reduced glutathione (GSH) content and superoxide dismutase (SOD) activity, demonstrating the overproduction of reactive oxygen species (ROS) and oxidative stress. Interestingly, PQS (125 and 250 mg/kg) can attenuate cisplatin-evoked changes in the above-mentioned parameters. Additionally, PQS administration significantly alleviated the oxidation resulted from inflammatory responses and apoptosis in cardiac tissues via inhibition of overexpressions of TNF-α, IL-1ß, Bax, and Bad as well as the caspase family members like caspase-3, and 8, respectively. CONCLUSION: Findings from our present research clearly indicated that PQS exerted significant effects on cisplatin-induced cardiotoxicity in part by inhibition of the NF-κB activity and regulation of PI3K/Akt/apoptosis mediated signaling pathways.

18.
Chem Asian J ; 14(21): 3855-3862, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31496032

RESUMO

In this work, we report a new mixed-extractor strategy to improve the sorting yield of large-diameter semiconducting single-walled carbon nanotubes (s-SWCNTs) with high purity. In the new mixed-extractor strategy, two kinds of conjugated polymers with different rigidity, poly(9,9-n-dihexyl-2,7-fluorene-alt-9-phenyl-3,6-carbazole) (PDFP) and poly(9,9-dioctylfluorene-alt-benzothiadiazole) (P8BT), are used to sort large-diameter s-SWCNTs through two simple sonication processes. To our surprise, although PDFP itself shows no selectivity toward s-SWCNTs, it can greatly enhance the sorting yield of P8BT. Using the PDFP/P8BT mixed-extractor method, the yield of sorted s-SWCNTs has been enhanced by 5 times with a purity above 99 % in comparison to that using P8BT single-extractor method. In addition, the photoluminescence (PL) excitation maps shows that the PDFP/P8BT mixed-extractor system not only enhances the sorting yield substantially, but also tends to be enrichment of (15,4) SWCNTs with the diameter of 1.36 nm.

19.
Aging (Albany NY) ; 11(17): 7123-7149, 2019 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-31495785

RESUMO

Polycomb group (PcG) proteins have recently been identified as critical regulators in tumor initiation and development. However, the function of CBX8 in human hepatocellular carcinoma (HCC) remains largely unknown. Our study was designed to explore the biological function and clinical implication of CBX8 in HCC. We investigated the interplay between CBX8 and cell cycle through Gene Set Enrichment Analysis and western blotting. Bioinformatics tools and co-immunoprecipitation were used to explore cell cycle regulation. Finally, we studied the expression and clinical significance of CBX8 in HCC through 3 independent datasets. CBX8 was upregulated in HCC and its expression correlated with cell cycle progression. CyclinD1 was downregulated by CBX8 knockdown but upregulated by CBX8 overexpression. YBX1 interacted with CBX8 and regulated the cell cycle. Moreover, targeting YBX1 with specific siRNA impaired CBX8-mediated regulation of CyclinD1. CBX8 overexpression boosted HCC cell growth, while CBX8 knockdown suppressed cell proliferation. Further, YBX1 interacted with CBX8. YBX1 knockdown compromised the proliferation of CBX8 overexpressing cells. CBX8 promotes HCC cell proliferation through YBX1 mediated cell cycle progression and is related to poor HCC prognoses. Therefore, CBX8 may serve as a potential target for the diagnosis and treatment of HCC.

20.
Front Microbiol ; 10: 1649, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31379793

RESUMO

The complete and efficient utilization of both glucose and xylose is necessary for the economically viable production of biofuels and chemicals using lignocellulosic feedstocks. Although recently obtained recombinant Saccharomyces cerevisiae strains metabolize xylose well when xylose is the sole carbon source in the medium (henceforth referred to as "X stage"), their xylose consumption rate is significantly reduced during the xylose-only consumption phase of glucose-xylose co-fermentation ("GX stage"). This post-glucose effect seriously decreases overall fermentation efficiency. We showed in previous work that THI2 deletion can alleviate this post-glucose effect, but the underlying mechanisms were ill-defined. In the present study, we profiled the transcriptome of a thi2Δ strain growing at the GX stage. Thi2p in GX stage cells regulates genes involved in the cell cycle, stress tolerance, and cell viability. Importantly, the regulation of Thi2p differs from a previous regulatory network that functions when glucose is the sole carbon source, which suggests that the function of Thi2p depends on the carbon source. Modeling research seeking to optimize metabolic engineering via TFs should account for this important carbon source difference. Building on our initial study, we confirmed that several identified factors did indeed increase fermentation efficiency. Specifically, overexpressing STT4, RGI2, and TFC3 increases specific xylose utilization rate of the strain by 36.9, 29.7, 42.8%, respectively, in the GX stage of anaerobic fermentation. Our study thus illustrates a promising strategy for the rational engineering of yeast for lignocellulosic ethanol production.

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