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1.
Molecules ; 25(5)2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32182775

RESUMO

We describe here a mechanistic study of the iron-catalyzed carboazidation of alkenes involving an intriguing metal-assisted ß-methyl scission process. Although t-BuO radical has frequently been observed in experiments, the ß-methyl scission from a t-BuO radical into a methyl radical and acetone is still broadly believed to be thermodynamically spontaneous and difficult to control. An iron-catalyzed ß-methyl scission of t-BuO is investigated in this work. Compared to a free t-BuO radical, the coordination at the iron atom reduces the activation energy for the scission from 9.3 to 3.9 ~ 5.2 kcal/mol. The low activation energy makes the iron-catalyzed ß-methyl scission of t-BuO radicals almost an incomparably facile process and explains the selective formation of methyl radicals at low temperature in the presence of some iron catalysts. In addition, a radical relay process and an outer-sphere radical azidation process in the iron-catalyzed carboazidation of alkenes are suggested by density functional theory (DFT) calculations.

2.
iScience ; 23(3): 100902, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32106054

RESUMO

Polymerization and modification play central roles in polymer chemistry and are generally implemented in two steps, which suffer from the time-consuming two-step strategy and present considerable challenge for complete modification. By introducing the radical cascade reaction (RCR) into polymer chemistry, a one-step strategy is demonstrated to achieve synchronized polymerization and complete modification in situ. Attributed to the cascade feature of iron-catalyzed three-component alkene carboazidation RCR exhibiting carbon-carbon bond formation and carbon-azide bond formation with extremely high efficiency and selectivity in one step, radical cascade polymerization therefore enables the in situ synchronized polymerization through continuous carbon-carbon bond formation and complete modification through carbon-azide bond formation simultaneously. This results in a series of α, ß, and γ poly(amino acid) precursors. This result not only expands the methodology library of polymerization, but also the possibility for polymer science to achieve functional polymers with tailored chemical functionality from in situ polymerization.

3.
Aging (Albany NY) ; 12(4): 3993-4009, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32074084

RESUMO

Metformin is one of the most commonly used first-line oral medications for type 2 diabetes mellitus. Multiple observational studies, reviewed in numerous systematic reviews, have shown that metformin treatment may not only reduce the risk of cancer but may also improve the efficacy of cancer treatment in diabetic patients. Recent studies have been conducted to determine whether a similar protective effect can be demonstrated in nondiabetic cancer patients. However, the results are controversial. The potential optimal dose, schedule, and duration of metformin treatment and the heterogeneity of histological subtypes and genotypes among cancer patients might contribute to the different clinical benefits. In addition, as the immune property of metformin was investigated, further studies of the immunomodulatory effect of metformin on cancer cells should also be taken into account to optimize its clinical use. In this review, we present and discuss the latest findings regarding the anticancer potential of metformin in nondiabetic patients with cancer.

4.
Acad Radiol ; 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31982342

RESUMO

RATIONALE AND OBJECTIVES: We assess the performance of a model combining a deep convolutional neural network and a hand-crafted radiomics signature for predicting KRAS status in patients with colorectal cancer (CRC). MATERIALS AND METHODS: The primary cohort consisted of 279 patients with clinicopathologically confirmed CRC between April 2011 and April 2015. Portal venous phase computed tomographic images were analyzed to extract traditional hand-crafted radiomics features as well as deep learning features. A Wilcoxon rank sum test, the minimum redundancy maximum relevance algorithm, and multivariable logistic regression analysis were used to select features and build a radiomics signature. A combined model was then developed using multivariable logistic regression analysis. An independent validation cohort of 119 patients from May 2015 to April 2016 was used to confirm the combined model's predictive performance. RESULTS: The C-index of hand-crafted radiomics signature's discriminative ability was 0.719 (95% confidence interval, CI: 0.658-0.776) for the primary cohort and 0.720 (95% CI: 0.625-0.813) for the validation cohort. The C-index of the deep radiomics signature's discriminative ability was 0.754 (95% CI: 0.696-0.813) for the primary cohort and 0.786 (95% CI: 0.702-0.863) for the validation cohort. The combined model, which merged the hand-crafted radiomics features and deep radiomics features, achieve a C-index of 0.815 (95% CI: 0.766-0.868) for the primary cohort and 0.832 (95% CI: 0.762-0.905) for the validation cohort. CONCLUSION: This study presents a model that incorporates the hand-crafted and deep radiomics signature, which can be used for individualized preoperative prediction of KRAS mutations in patients with CRC.

5.
Inflammation ; 43(1): 32-43, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31894450

RESUMO

Air pollution events frequently occur in China during the winter. Most investigations of pollution studies have focused on the physical and chemical properties of PM2.5. Many of these studies have indicated that PM2.5 exacerbates asthma or eosinophil inflammation. However, few studies have evaluated the relationship between bacterial loads in PM2.5, and especially pathogenic bacteria and childhood asthma. Airborne PM2.5 samples from heavily polluted air were collected in Hangzhou, China between December 2014 and January 2015. PM2.5 and ovalbumin (OVA) were intratracheally administered twice in 4-week intervals to induce the allergic pulmonary inflammation in adolescent C57/BL6 mice. PM2.5 exposure caused neutrophilic alveolitis and bronchitis. In the presence of OVA, the levels of the Th2 cytokines IL-4, IL-12, and IL-17 were significantly increased in bronchoalveolar lavage fluids (BALF) after PM2.5 exposure, while eosinophil infiltration and mucin secretion were also induced. In addition to adjuvant effects on OVA-induced allergic inflammation, PM2.5 exposure also led to the maturation of dendritic cells. These results suggest that PM2.5 exposure may aggravate lung eosinophilia and that PM2.5-bound microbial can exacerbate allergic and inflammatory lung diseases.

6.
Nat Commun ; 11(1): 416, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964875

RESUMO

Organofluorine compounds have shown their great value in many aspects. Moreover, allenes are also a class of important compounds. Fluorinated or fluoroalkylated allenes might provide an option as candidates for drug and material developments, as allenes allow a great number of valuable transformations. Herein, we report a metal-free synthesis of difluoromethylated allenes via regioselective trifunctionalization of 1,3-enynes. This method proceeds through double C-F bond formation with concomitant introduction of an amino group to the allene. Synthetic applications are conducted and preliminary mechanistic studies suggest that a two-step pathway is involved. DFT calculations revealed an unusual dibenzenesulfonimide-assisted fluorination/fluoroamination with NFSI. In addition, kinetic reaction study revealed the induction period of both major and side products to support the proposed reaction mechanism. This work offers a convenient approach for the synthesis of a range of difluoromethylated allenes and is also a rare example of trifunctionalization of 1,3-enynes.

7.
Plant Physiol Biochem ; 147: 272-279, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31891861

RESUMO

Virus-induced gene silencing (VIGS) is a technology for rapid gene functional analysis that depends on the degradation of viral RNA and is part of the natural defense mechanism in plants. Senecio cruentus is an important Compositae ornamental species that is plentiful and available in a variety of colors and has a typical blue variety that is rare in Compositae. These advantages make it a good material for studying the anthocyanin biosynthesis and blue flower formation mechanism. With the development of gene sequencing technology, the functions of many candidate genes that may be involved in anthocyanin biosynthesis in S. cruentus need to be identified. However, a stable and rapid genetic transformation system of S. cruentus is still lacking. Here, we screened two cultivars, 'Venezia' and 'Jseter', selected ScPDS and ScANS as test genes, and investigated the effect of developmental periods, bacterial cell concentrations and infection methods on gene silencing efficiency. The results showed that the silencing efficiency of S. cruentus leaves was low (13%), and it was less affected by the parameters. However, the transcription factor gene ScbHLH17 was still silenced by VIGS, which resulted in the loss of anthocyanin accumulation in leaves, and the expression levels of anthocyanin biosynthesis pathway (ABP) structural genes, including ScCHI, ScDFR3 and ScANS, were decreased significantly. The result proved that ScbHLH17 was an important transcription factor that regulated flower color formation in S. cruentus. In addition, ScANS-silencing phenotypes were observed in S. cruentus capitulum by vacuum-infiltrating S1 stage buds for 10 min after scape injection. In general, the present study provided an important technical support for the study of anthocyanin metabolism pathways in S. cruentus.

8.
Org Lett ; 22(3): 991-996, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31967845

RESUMO

α-Deuterated alcohols have important applications in pharmaceuticals and mechanism studies. Here, we report a new and practical strategy for the reductive deuteration of ketones using a Mg/BrCH2CH2Br/D2O system, which affords α-deuterated alcohols in good yields and with almost quantitative incorporation of deuterium. The synthetic value of this method has been demonstrated by the easy access to deuterated drugs or drug derivatives. This method may inspire the discovery of other deuterium-containing drugs.

9.
Cancer Med ; 9(1): 290-301, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31709750

RESUMO

BACKGROUND: Early detection of urothelial carcinoma (UC) by noninvasive diagnostic methods with high accuracy is still underscored. This study aimed to develop a noninvasive assay incorporating both enrichment of urine exfoliated cells and immunoassays for UC detection. METHODS: Polystyrene dishes were exposed to oxygen plasma and modified with 3-aminopropyltriethoxysilane to prepare amine-functionalized nanostructured substrates (NS). Performance characterization of NS was evaluated by atomic force microscope and X-ray photoelectron spectroscopy. Urine exfoliated cells were captured by NS and then immunostained to detect urinary tumor cells (UTCs), which was called UTC assay. The receiver operating characteristic (ROC) curve, area under ROC curve (AUC), and Youden index were used to find the cutoff value of UTC assay. ROC analysis and McNemar test were used to compare the diagnostic accuracy of UTC assay with cytology. Kappa test was used to analyze the agreement of UTC assay and cytology with pathological diagnosis. RESULTS: Nanostructured substrates had good cell binding yields of nucleated cells and tumor cells. CK20+ CD45- CD11b- cells were considered as UTCs. UTC number ≥ 1 per sample could be considered as a positive result. By AUC and Kappa analysis, UTC assay showed good performance in UC detection. McNemar test demonstrated that UTC assay had a superior sensitivity even in low-grade subgroup and a similar specificity compared to cytology in UC diagnosis. CONCLUSIONS: Nanostructured substrates could be used to enrich the exfoliated cells from urine samples. UTC assay with NS has the potential to play a role in UC detection. The value of this assay still needs additional validation by large, multi-center studies.

10.
Chemosphere ; 241: 125013, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31604199

RESUMO

In this study, we investigated the phytotoxicity of an imidazolium-based ionic liquid, 1-allyl-3-methylimidazolium chloride ([Amim]Cl), against maize seedlings. It was found that in response to an increase in [Amim]Cl treatment concentrations, there were significant decreases in growth parameters (fresh weights and lengths) and the photosynthetic pigment contents of maize plants, whereas in contrast, the malondialdehyde content increased. In order to determine the molecular basis of [Amim]Cl-induced plant growth inhibition, an RNA-Seq analysis to examine the gene expression profiles of selected central biological pathways was performed. And a total of 4024 genes that were differentially expressed between control and 400 mg/L [Amim]Cl-treated plants were accordingly identified. Pathway enrichment analysis for the differentially expressed genes revealed that 12 of 15 genes in the porphyrin and chlorophyll metabolic pathways were down-regulated in response to [Amim]Cl treatment. Moreover, all six genes encoding key chlorophyll synthetic enzymes were down-regulated by [Amim]Cl. With regards to plant hormone metabolic pathways, the genes encoding key enzymes involved in ethybilene and abscisic acid (ABA) biosynthesis were up-regulated in response to [Amim]Cl treatment. Genes responsible for gibberellin (GA) inactivation were also stimulated by [Amim]Cl. These observations indicate that [Amim]Cl may promote the biosynthesis of senescence-related hormones (ethylene and ABA) as well as inactivation of growth-promoting hormones (GAs). It might be concluded that the observed [Amim]Cl-induced inhibition of maize seedling growth could be associated with changes in the gene expression profiles of these metabolic pathways.


Assuntos
Compostos Alílicos/farmacologia , Perfilação da Expressão Gênica , Imidazóis/farmacologia , Reguladores de Crescimento de Planta/metabolismo , Plântula/efeitos dos fármacos , Zea mays/metabolismo , Compostos Alílicos/toxicidade , Clorofila/metabolismo , Genes de Plantas , Imidazóis/toxicidade , Redes e Vias Metabólicas/genética , Fotossíntese/efeitos dos fármacos , Plântula/genética , Plântula/crescimento & desenvolvimento , Plântula/metabolismo , Zea mays/crescimento & desenvolvimento
11.
Artigo em Inglês | MEDLINE | ID: mdl-31812005

RESUMO

Pingyangmycin (PYM) and boanmycin (BAM), two individual components of bleomycin (bleomycin A5 and bleomycin A6), are glycopeptide antitumor antibiotics. An efficient procedure for the preparation of PYM and BAM from Streptomyces verticillus var. pingyangensis fermentation broth using macroporous cation-exchange (MCE) resin followed by medium-pressure preparative liquid chromatography (MPLC) based on monodisperse poly(styrene-co-divinylbenzene) (p(st-dvb)) microspheres was investigated in this paper. Nine frequently used MCE resins were screened by static adsorption and desorption to enrich PYM and BAM fromthe fermentation broth, and D157 resin was found to be the most effective. After one run of column-based dynamic adsorption and desorption, the contents of PYM and BAM were increased by factors of 13.8 and 12.1 with recovery yields of 84.21% and 81.47%, respectively. The enriched samples were subjected to MPLC with columns prepacked with the PolyRP 10-300 microspheres. The operational parameters of the MPLC, including the stationary phase and mobile phase compositions, sample/stationary phase ratio, sample loading scale and flow rate, were screened and optimized. The results showed that the separation and purification for PYM and BAM by MPLC were dramatically improved with a mobile phase modifier of 0.15 mol/L ammonium chloride aqueoussolution, a flow rate of 10 mL/min and a sample/stationary phase ratio of 1.0:100 (m/v, g/mL), and PYM and BAM with purities of more than 98.65% and 99.12% were obtained, respectively. The total recoveries of PYM and BAM reached 75.38% and 70.31%. The separation and purification method is simple, efficient, energy-saving, environmentally friendly and suitable for the large-scale preparation of high-purity PYM and BAM from Streptomyces verticillus var. pingyangensis fermentation broth.

12.
Lancet Oncol ; 21(2): 306-316, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31879220

RESUMO

BACKGROUND: Extranodal natural killer T-cell lymphoma (NKTCL; nasal type) is an aggressive malignancy with a particularly high prevalence in Asian and Latin American populations. Epstein-Barr virus infection has a role in the pathogenesis of NKTCL, and HLA-DPB1 variants are risk factors for the disease. We aimed to identify additional novel genetic variants affecting risk of NKTCL. METHODS: We did a genome-wide association study of NKTCL in multiple populations from east Asia. We recruited a discovery cohort of 700 cases with NKTCL and 7752 controls without NKTCL of Han Chinese ancestry from 19 centres in southern, central, and northern regions of China, and four independent replication samples including 717 cases and 12 650 controls. Three of these independent samples (451 cases and 5301 controls) were from eight centres in the same regions of southern, central, and northern China, and the fourth (266 cases and 7349 controls) was from 11 centres in Hong Kong, Taiwan, Singapore, and South Korea. All cases had primary NKTCL that was confirmed histopathologically, and matching with controls was based on geographical region and self-reported ancestry. Logistic regression analysis was done independently by geographical regions, followed by fixed-effect meta-analyses, to identify susceptibility loci. Bioinformatic approaches, including expression quantitative trait loci, binding motif and transcriptome analyses, and biological experiments were done to fine-map and explore the functional relevance of genome-wide association loci to the development of NKTCL. FINDINGS: Genetic data were gathered between Jan 1, 2008, and Jan 23, 2019. Meta-analysis of all samples (a total of 1417 cases and 20 402 controls) identified two novel loci significantly associated with NKTCL: IL18RAP on 2q12.1 (rs13015714; p=2·83 × 10-16; odds ratio 1·39 [95% CI 1·28-1·50]) and HLA-DRB1 on 6p21.3 (rs9271588; 9·35 × 10-26 1·53 [1·41-1·65]). Fine-mapping and experimental analyses showed that rs1420106 at the promoter of IL18RAP was highly correlated with rs13015714, and the rs1420106-A risk variant had an upregulatory effect on IL18RAP expression. Cell growth assays in two NKTCL cell lines (YT and SNK-6 cells) showed that knockdown of IL18RAP inhibited cell proliferation by cell cycle arrest in NKTCL cells. Haplotype association analysis showed that haplotype 47F-67I was associated with reduced risk of NKTCL, whereas 47Y-67L was associated with increased risk of NKTCL. These two positions are component parts of the peptide-binding pocket 7 (P7) of the HLA-DR heterodimer, suggesting that these alterations might account for the association at HLA-DRB1, independent of the previously reported HLA-DPB1 variants. INTERPRETATION: Our findings provide new insights into the development of NKTCL by showing the importance of inflammation and immune regulation through the IL18-IL18RAP axis and antigen presentation involving HLA-DRB1, which might help to identify potential therapeutic targets. Taken in combination with additional genetic and other risk factors, our results could potentially be used to stratify people at high risk of NKTCL for targeted prevention. FUNDING: Guangdong Innovative and Entrepreneurial Research Team Program, National Natural Science Foundation of China, National Program for Support of Top-Notch Young Professionals, Chang Jiang Scholars Program, Singapore Ministry of Health's National Medical Research Council, Tanoto Foundation, National Research Foundation Singapore, Chang Gung Memorial Hospital, Recruitment Program for Young Professionals of China, First Affiliated Hospital and Army Medical University, US National Institutes of Health, and US National Cancer Institute.

13.
Org Lett ; 22(2): 620-625, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31855441

RESUMO

A Cu-catalyzed synthesis of a range of value-added 1,1-diarylalkanes by radical alkylarylation of vinylarenes with alkyl peroxides as masked alkyl electrophiles is reported. The reaction features broad substrate scope, good functional group tolerance, and mild reaction conditions. Various bioactive molecules and key pharmaceutical intermediates have been easily synthesized by this method, demonstrating its synthetic value.

14.
Cancer Manag Res ; 11: 9439-9448, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31807073

RESUMO

Purpose: This study aimed to develop and validate a nomogram for predicting the malignancy of small (8-20 mm) solid indeterminate solitary pulmonary nodules (SPNs) in a Chinese population by using routine clinical and computed tomography data. Methods: The prediction model was developed using a retrospective cohort that comprised 493 consecutive patients with small indeterminate SPNs who were treated between December 2012 and December 2016. The model was independently validated using a second retrospective cohort comprising 216 consecutive patients treated between January 2017 and May 2018. The investigated variables included patient characteristics (e.g., age and smoking history), nodule parameters (e.g., marginal spiculation and significant enhancement), and tumor biomarker levels (e.g., carcinoembryonic antigen). A prediction model was developed by using multivariable logistic regression analysis, and the model's performance was presented as a nomogram. The model was evaluated based on its discriminative ability, calibration, and clinical usefulness. Results: The developed nomogram was ultimately based on age, marginal spiculation, significant enhancement, and pleural indentation. The Harrell concordance index values were 0.869 in the training cohort (95% confidence interval: 0.837-0.901) and 0.847 in the validation cohort (95% confidence interval: 0.792-0.902). The Hosmer-Lemeshow test revealed good calibration in each of the training and validation cohorts. Decision curve analysis confirmed that the nomogram was clinically useful (risk threshold from 0.10 to 0.85). Conclusion: Patient age, marginal spiculation, significant enhancement, and pleural indentation are independent predictors of malignancy in small indeterminate solid SPNs. The developed nomogram is easy-to-use and may allow the accurate prediction of malignancy in small indeterminate solid SPNs among Chinese patients.

15.
Onco Targets Ther ; 12: 8841-8851, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31802897

RESUMO

Purpose: In previous studies, we confirmed that the overexpression of lncRNA NORAD was associated with the occurrence and development of gastric cancer (GC). The aim of the present study was to explore the molecular mechanism of lncRNA NORAD on GC cell proliferation and apoptosis in vitro and in vivo. Patients and methods: The quantitative Real-Time PCR (qRT-PCR) was used to determine the expression levels of lncRNA NORAD and miR-214 in GC tissues and cells. The interaction between lncRNA NORAD and miR-214 was investigated by biological information and Dual-Luciferase gene reporter assay. Effect of lncRNA NORAD on GC tumor growth in vivo was studied in tumor xenograft model mice. The apoptosis of GC cells was determined by flow cytometry. The proliferation of GC cells was determined by 5-ethynyl-2´-deoxyuridine (EDU) and colony formation assays. Western Blot was used to determine the expressions of caspase-3, Akt and mTOR in GC tissues and cells. Results: The qRT-PCR results showed that lncRNA NORAD was highly expressed in human GC tissues and cell lines, while miR-214 was significantly down-regulated. Meanwhile, there was a direct interaction between lncRNA NORAD and miR-214. In addition, lncRNA NORAD could promote the growth and proliferation of GC cells both in vivo and in vitro. NOARD could also inhibit the apoptosis of GC cells by down-regulating caspase-3; however, miR-214 overexpression attenuated this effect. Moreover, lncRNA NORAD promoted the phosphorylation of Akt and mTOR in mouse GC tissues and GC cell lines, while miR-214 mimics inhibited that promotion. Conclusion: These results suggested that NORAD could promote the development of GC by inhibiting miR-214 expression and activating the Akt/mTOR signaling pathway.

16.
BMC Cardiovasc Disord ; 19(1): 244, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694566

RESUMO

BACKGROUND: The independent association of neck circumference (NC) on elevated blood pressure is still uncertain in adults of China. The aim of this study is to explore such association and investigate the predictive value of NC on hypertension. METHODS: A total of 4279 adults aged 20-80 years participated in the cross-sectional study in 2014. Anthropometric information, NC, body composition indexes such as waist circumference, hip circumference and body fat percentage, and blood pressure were measured. General linear regression model was used to explore the association between NC and blood pressure; Logistic regression models were fitted to calculate the multi-variable adjusted prevalence, and the association of NC with hypertension. RESULTS: The overall prevalence of hypertension and pre-hypertension were 11.05 and 23.63%, respectively. NC was positively associated with both SBP and DBP (p < 0.001). The adjusted prevalence of hypertension increased with elevated NC quartiles in both sexes (p for trend < 0.001), from 17.81 to 42.93% in male and 9.72 to 21.31% in female. For male, NC was only associated with hypertension (OR: 1.15, 95% CI: 1.05-1.25) but not with pre-hypertension (OR: 0.97, 95% CI: 0.88-1.06). However, in female, NC was associated with both pre-hypertension and hypertension, the BMI adjusted ORs were 1.15 (1.03-1.28) and 1.24 (1.14-1.34). The sex-specific AUCs for NC predicting hypertension were 0.633 in male and 0.663 in female, similar with AUCs of other body fat indexes. CONCLUSIONS: NC was associated with both pre-HTN and HTN independent from other body composition indexes. NC is a simple and useful anthropometric index to identify elevated blood pressure in Chinese adults.

17.
Front Plant Sci ; 10: 1147, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695707

RESUMO

Calcium-dependent protein kinases (CDPKs) are recognized as important calcium (Ca2+) sensors in signal transduction and play multiple roles in plant growth and developmental processes, as well as in response to various environmental stresses. However, little information is available about the CDPK family in the green microalga Chlamydomonas reinhardtii. In this study, 15 CrCDPK genes were identified in C. reinhardtii genome, and their functions in nitrogen (N) deficiency-induced oil accumulation were analyzed. Our results showed that all CrCDPK proteins harbored the typical elongation factor (EF)-hand Ca2+-binding and protein kinase domains. Phylogenetic analysis revealed that these CrCDPKs were clustered into one group together with a subclade of several CPKs from Arabidopsis and rice, clearly separating from the remaining AtCPKs and OsCPKs. These genes were located in 10 chromosomes and one scaffold of C. reinhardtii and contained 6-17 exons. RNA sequencing and quantitative reverse transcription (qRT)-PCR assays indicated that most of these CrCDPKs were significantly induced by N deficiency and salt stress. Lanthanum chloride (LaCl3), a plasma membrane Ca2+ channel blocker, limited oil accumulation in C. reinhardtii under N-deficient conditions, suggesting that Ca2+ was involved in N deficiency-induced oil accumulation. Furthermore, RNA interference (RNAi) silencing analyses demonstrated that six CrCDPKs played positive roles and three CrCDPKs played negative roles in N deficiency-induced oil accumulation in C. reinhardtii.

18.
Medicine (Baltimore) ; 98(44): e17867, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31689880

RESUMO

AIMS: Interleukin(IL)-22 plays an important role in promoting liver regeneration and repair, but its role in chronic HBV-related liver diseasesis not clear. The goal of this study was to evaluate associations between eight IL22 single nucleotide polymorphisms (SNPs) and the development of chronic HBV cirrhosis and HBV-related HCC within a Chinese Han population. METHODS: We investigated associations between single nucleotide polymorphisms (SNPs) in the IL22 gene (rs1026788, rs2227472, rs2227491, rs2227485, rs1179249, rs2046068,rs2227473, and rs7314777) and the risk of HBV-related chronic liver diseases within a Han population in Northeast China. A total of 649 participants were included in the study, including 103 patients with CHB, 264 patients with LC, and 282 patients with HCC. The odds ratios (OR) and corresponding 95% confidence intervals (CI) were calculated using chi-square test. Haplotype analysis was conducted by haploview software. RESULTS: Genotype and allele distributions of SNPs rs1179249 and rs2227472 differed between LC and CHB groups (both P < 0.05).The G alleles of SNP rs2227491 and rs1026788 were more frequent in the LC group than in the CHB group (P = 0.046, P = 0.041 respectively). A IL22 haplotype consisting of the minor alleles of SNP rs1179249 and the major alleles of seven other SNPs occurred less frequently in the LC and HCC groups than in the CHB group (28.2%, 33.94%, and 37.86%, respectively, P < 0.05). Moreover, there were no significant associations between smoking or drinking and IL22 SNPs on the risk of HCC (P > 0.05). CONCLUSION: IL22 genetic variations were associated with chronic HBV infection progression, especially in the HBV-LC group. The IL22 genetic variations may help clinicians initiate the correct treatment strategy at the CHB stage.


Assuntos
Carcinoma Hepatocelular/virologia , Hepatite B Crônica/genética , Interleucinas/genética , Cirrose Hepática/virologia , Neoplasias Hepáticas/virologia , Polimorfismo de Nucleotídeo Único , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Grupo com Ancestrais do Continente Asiático/genética , Carcinoma Hepatocelular/genética , Estudos de Casos e Controles , Progressão da Doença , Feminino , Hepatite B Crônica/complicações , Humanos , Cirrose Hepática/genética , Neoplasias Hepáticas/genética , Masculino , Pessoa de Meia-Idade , Mutação Puntual , Estudos Retrospectivos , Fumar/efeitos adversos
19.
Life Sci ; 238: 116962, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31628913

RESUMO

AIMS: Electroacupuncture (EAc) has a pulmonary protective effect during cardiopulmonary bypass (CPB), but its molecular mechanisms including inflammasome activation signaling pathways remains unclear. MATERIALS AND METHODS: Male Sprague Dawley rats were divided into control, CPB + EAc and CPB groups. Lung injury model was developed by CPB treatment and EAc (2/100 Hz) was carried out before CPB in the CPB + EAc group. Lung tissues were collected at two time points (0.5 h; 2 h) to determine cytokines release by ELISA kits, and protein expressions by Western blot. Serum collected at two time points (0.5 h; 2 h) from CPB and CPB + EAc treated groups were used in NR8383 cells to confirm the effect of EAc. KEY FINDINGS: CPB significantly increased the inflammatory mediators, histological damage and expression of inflammasome related protein and apoptosis, when compared with control group. The level of tumor necrosis factor-α(TNF-α), interleukin (IL)-18 and IL-1ß in the CPB + EAc treated group was significantly decreased along with histological changes compared to CPB. Moreover, EAc inhibited the activation of Nod like receptor protein-3 (NLRP3) inflammasome complex, caspase-8 and activated NF-E2-related factor 2 (p-Nrf2). In addition, serum from the CPB + EAc group prevented CPB induced activation of inflammasome and related mediators, reducing ROS generation and apoptosis in NR8383 macrophages. SIGNIFICANCE: These findings indicate that EAc had a critical anti-apoptotic role by suppression of ROS/Nrf2/NLRP3 inflammasome pathway. EAc might be a possible therapeutic treatment for CPB-induced acute lung injury.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Apoptose , Ponte Cardiopulmonar/efeitos adversos , Eletroacupuntura/métodos , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Inflamassomos , Masculino , Ratos , Ratos Sprague-Dawley
20.
Plant Physiol Biochem ; 142: 415-428, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31416008

RESUMO

The variation of flower color of chrysanthemum (Chrysanthemum×morifolium) is extremely rich, and carotenoids, which are mainly stored in the plastid, are important pigments that determine the color of chrysanthemum. However, the genetic regulation of the carotenoid metabolism pathway in this species still remains unclear. In this study, a pink chrysanthemum cultivar, 'Jianliuxiang Pink', and its three bud sport mutants (including white, yellow and red color mutants, 'Jianliuxiang White', 'Jianliuxiang Yellow' and 'Jianliuxiang Red', respectively) were used as experimental materials to analyze the dynamic changes of carotenoid components and plastid ultrastructure at different developmental stages of ray florets. We found that the carotenoid components and plastid ultrastructure of the four color cultivars in the early developmental stage of the chrysanthemum capitulum (S1) were almost identical, and the carotenoids mainly included violaxanthin, lutein and ß-carotene, which exist in proplastids and immature chloroplasts. With the development of capitulum, the chloroplasts in 'Jianliuxiang White' and 'Jianliuxiang Pink' were degraded, and the protoplasts did not transform but rather formed vesicles that accumulated trace amounts of carotenoids. The proplastids and chloroplasts in 'Jianliuxiang Yellow' and 'Jianliuxiang Red' were all transformed into chromoplasts and consist of lutein as well as lutein's isomer and derivatives. Using comparative transcriptomics combined with gene expression analysis, we found that CmPg-1, CmPAP10, and CmPAP13, which were involved in chromoplast transformation, CmLCYE, which was involved in carotenoid biosynthesis, and CmCCD4a-2, which was involved in carotenoid degradation, were differentially expressed between four cultivars, and these key genes therefore should affect the accumulation of carotenoids in chrysanthemum. In addition, six transcription factors, CmMYB305, CmMYB29, CmRAD3, CmbZIP61, CmAGL24, CmNAC1, were screened using weighted gene co-expression correlation network analysis (WGCNA) combined with correlative analysis to determine whether they play an important role in carotenoid accumulation by regulating structural genes related to the carotenoid metabolism pathway and plastid development. This study analyzed dynamic changes of carotenoid components and plastid ultrastructure of the four bud mutation cultivars of chrysanthemum and identified structural genes and transcription factors that may be involved in carotenoid accumulation. The above results laid a solid foundation for further analysis of the regulatory mechanism of the carotenoid biosynthesis pathway in chrysanthemum.


Assuntos
Carotenoides/metabolismo , Chrysanthemum/metabolismo , Carotenoides/análise , Cromatografia Líquida de Alta Pressão , Chrysanthemum/química , Chrysanthemum/genética , Cor , Flores/química , Flores/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/genética , Genes de Plantas , Redes e Vias Metabólicas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/fisiologia , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição/genética , Fatores de Transcrição/fisiologia , Transcriptoma
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