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1.
Food Chem ; 320: 126684, 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32229394

RESUMO

Refrigeration is used to retard senescence and extend the storage life of 'Nanguo' pears, but fruits subjected to long-term refrigeration are prone to pericarp browning during subsequent shelf life. To uncover the potential effects of membrane lipid changes during fruit pericarp browning, changes in fruit appearance and cell ultrastructure were observed after different storage durations. Membrane lipid content as well as the activity and gene expression of enzymes involved in membrane lipid metabolism and membrane stability were analyzed. Results showed that long-term refrigeration increased the activity and expression of PLD, LOX, lipase, and membrane stability-related genes that promoted membrane lipid degradation and peroxidation, reduced membrane lipid unsaturation, and led to severe browning. Overall, membrane instability induced by disordered membrane lipid metabolism under low temperature stress may account for pericarp browning of cold stored 'Nanguo' pears.

2.
Chem Commun (Camb) ; 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32239070

RESUMO

The limited discharge capacity of LiCoO2 can be improved by increasing its working potential, but it suffers from Co4+ dissolution and decomposition of the electrolyte. Nitriles have attracted great interest as high-voltage electrolytes due to their wide electrochemical window. However, the cathodic interfacial stability of nitrile electrolytes with a high-voltage LiCoO2 cathode has yet to be explored. Herein, we adopted an SN-based deep eutectic electrolyte with SN as the only solvent and found that Co4+ could be reduced by the SN solvent on the interface of the LiCoO2 electrode, causing a reverse phase change of LiCoO2 and severe self-discharge of the LiCoO2|Li and LiCoO2|Li4Ti5O12 batteries. When LiDFOB was introduced into the electrolyte, the self-discharge behavior of cells could be largely decelerated. The series of characterizations performed in our work revealed that the cathode/electrolyte interface generated from the LiDFOB salt could stabilize the interface of LiCoO2 and suppress the dissolution of the ions of the transition metal Co.

3.
Mol Med Rep ; 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32236614

RESUMO

Non-small-cell lung cancer (NSCLC) is the fundamental form of lung cancer and the leading cause of cancer­related mortality in humans. Numerous studies have identified a role for microRNAs (miRs) in cell proliferation, invasion and metastasis in numerous types of cancer, including lung cancer. In the present study, the functional roles and molecular mechanisms of miR­28 in NSCLC tumorigenesis were investigated. Reverse transcription­quantitative PCR (RT­qPCR) was used to measure miR­28 expression levels in NSCLC tumor tissues and cell lines. A dual­luciferase assay was performed to observe the direct interaction between miR­28 and PTEN in A549 cells. Furthermore, the effect of miR­28 on the mRNA and protein expression levels of PTEN was examined by RT­qPCR and western blotting, respectively. A Cell Counting kit­8 assay was performed to identify the relationship between the miR­28/PTEN axis and tumor cell proliferation using cells infected with lentivirus (LV)­anti­miR­28 or LV­anti­miR­28 + short hairpin RNA­PTEN. miR­28 expression was upregulated in NSCLC tumor tissues and cell lines compared with the control groups. PTEN was identified as the downstream gene of miR­28 in NSCLC and was negatively regulated by miR­28. In addition, miR­28 knockdown suppressed the proliferation of A549 and H292 cells. Cells infected with LV­anti­miR­28 + short hairpin RNA­PTEN promoted tumor cell proliferation in A549 and H292 cells compared with cells infected with LV­anti­miR­28. Taken together, the present study suggested that miR­28 might serve as the promoter in the development of NSCLC by targeting PTEN. Therefore, the miR­28/PTEN axis may serve as a potential diagnostic and therapeutic target for NSCLC.

4.
Mol Reprod Dev ; 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32215983

RESUMO

BRG1-associated factor 250a (BAF250a) is a component of the SWI/SNF adenosine triphosphate-dependent chromatin remodeling complex, which has been shown to control chromatin structure and transcription. BAF250a was reported to be a key component of the gene regulatory machinery in embryonic stem cells controlling self-renewal, differentiation, and cell lineage decisions. Here we constructed Baf250aF/F ;Gdf9-cre (Baf250aCKO ) mice to specifically delete BAF250a in oocytes to investigate the role of maternal BAF250a in female germ cells and embryo development. Our results showed that BAF250a deletion did not affect folliculogenesis, ovulation, and fertilization, but it caused late embryonic death. RNA sequencing analysis showed that the expression of genes involved in cell proliferation and differentiation, tissue morphogenesis, histone modification, and nucleosome remodeling were perturbed in Baf250aCKO MII oocytes. We showed that covalent histone modifications such as H3K27me3 and H3K27ac were also significantly affected in oocytes, which may reduce oocyte quality and lead to birth defects. In addition, the DNA methylation level of Igf2r, Snrpn, and Peg3 differentially methylated regions was decreased in Baf250aCKO oocytes. Quantitative real-time polymerase chain reaction analysis showed that the relative messenger RNA (mRNA) expression levels of Igf2r and Snrpn were significantly increased. The mRNA expression level of Dnmt1, Dnmt3a, Dnmt3l, and Uhrf1 was decreased, and the protein expression in these genes was also reduced, which might be the cause for impaired imprinting establishment. In conclusion, our results demonstrate that BAF250a plays an important role in oocyte transcription regulation, epigenetic modifications, and embryo development.

5.
Zhongguo Gu Shang ; 33(2): 99-105, 2020 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-32133805

RESUMO

OBJECTIVE: To explore the application value of 3D printing technology in preoperative surgery plan and intraoperative auxiliary operation for adult kyphoscoliosis deformity. METHODS: The clinical data of 12 adult patients with kyphoscoliosis deformity treated from September 2017 to January 2019 were retrospectively analyzed. There were 3 males and 9 females, aged from 21 to 63 years old with an average of (47.67±13.32) years old. Among them, 4 cases were congenital kyphoscoliosis, 2 cases were old tuberculosis thoracolumbar kyphosis ; 2 cases were idiopathic kyphoscoliosis, 4 cases were degenerative kyphoscoliosis. The CT scan data of the patient's spine was imported into Mimics17.0 software to establish the three dimensional model of the spine, and the spine model was produced by 3D printer. Using the spine model simulated operation, preoperative surgery program planning and formulated a precise surgery, and further analysed postoperative imaging parameters improvement. All the patients were followed up for more than 1 year. Before and after operation and at the last follow-up, the scoliosis Cobb angle, maximum kyphosis Cobb angle, and coronal plane balance (distance between C 7 plumbline and center sacral vertical line, C7PL-CSVL), sagittal plane balance (sagittal vertical axis, SVA), pelvic parameters and other related imaging parameters were measured to further evaluate its orthopedic effect. RESULTS: Twelve patients with spine deformity were treated with different osteotomy and internal fixation fusion methods under the guidance of a 1∶1 spine model (pedicle screw placement of 4 patients with severe deformity were assisted by pedicle screw guide plates), nail placement and osteotomy have good effects, no major tissue damage such as blood vessels, nerves and spinal cord during and after surgery, no complications such as cerebrospinal fluid leakage and infection. Preoperative Cobb angle of scoliosis was (56.5±22.5) °, Cobb angle of kyphosis was (65.2±19.5) °, C7 PL-CSVL was (45.8±16.9) mm, SVA was (48.7±25.4) mm. Postoperative at 4 weeks, Cobb angle of scoliosis was (20.8±11.5) °, and Cobb angle of kyphosis was (22.0±6.6) °, with correction rates of (65.1±9.7)% and (64.6± 10.6)%, respectively ; C7 PL-CSVL was (22.3±8.9) mm, and SVA was (23.3±13.1) mm, all of which were significantly improved compared with preoperative results. The mean follow-up time was (18.5±7.9) months in 12 patients. At the last follow-up, the Cobb angles of scoliosis and kyphosis were (22.2±10.8) ° and (23.6±7.7) °, respectively, C7 PL-CSVL was (23.5±10.8) mm, and SVA was (24.7±12.5) mm. The results were statistically significant compared preoperative (P<0.05). There was no significant difference at the postoperative at 4 weeks and the last follow-up (P>0.05). CONCLUSION: The 3D print model can visually and clearly show the vertebral morphology and structure of adult kyphoscolisis and its spatial relationship with the adjacent vertebrae, blood vessels, and nerves, which provides a good and intuitive stereoscopic anatomical structure observation for the individualization of the surgical plan. Pre-simulation of operations to determine the internal fixation, fusion segment and osteotomy orthopedic way, may to provide a reference for actual clinical surgery, and can improve the accuracy and safety of surgery.


Assuntos
Cifose , Parafusos Pediculares , Escoliose , Fusão Vertebral , Adulto , Feminino , Humanos , Cifose/diagnóstico por imagem , Cifose/cirurgia , Masculino , Pessoa de Meia-Idade , Impressão Tridimensional , Estudos Retrospectivos , Escoliose/diagnóstico por imagem , Escoliose/cirurgia , Resultado do Tratamento , Adulto Jovem
7.
Zool Res ; 41(2): 123-137, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32150792

RESUMO

Interleukin-34 (IL-34) is a novel cytokine that plays an important role in innate immunity and inflammatory processes by binding to the colony-stimulating factor-1 receptor (CSF-1R). However, information on the function of IL-34 in fish remains limited. In the present study, we identified an IL-34 homolog from mudskippers ( Boleophthalmus pectinirostris). In silico analysis showed that the mudskipper IL-34 (BpIL-34) was similar to other known IL-34 variants in sequence and structure and was most closely related to an orange-spotted grouper ( Epinephelus coioides) homolog. BpIL-34 transcripts were constitutively expressed in various tissues, with the highest level of expression found in the brain. Edwardsiella tarda infection significantly up-regulated the mRNA expression of BpIL-34 in the mudskipper tissues. The recombinant mature BpIL-34 peptide (rBpIL-34) was purified and used to produce anti-rBpIL-34 IgG. Western blot analysis combined with PNGase F digestion revealed that native BpIL-34 in monocytes/macrophages (MOs/MФs) was N-glycosylated. In vitro, rBpIL-34 treatment enhanced the phagocytotic and bactericidal activity of mudskipper MOs/MФs, as well as the mRNA expression of pro-inflammatory cytokines like tumor necrosis factor α ( BpTNF-α) and BpIL-1ß in these cells. Furthermore, the knockdown of mudskipper CSF-1R1 ( BpCSF-1R1), but not mudskipper BpCSF-1R2, significantly inhibited the rBpIL-34-mediated enhanced effect on MO/MФ function. In conclusion, our results indicate that mudskipper BpIL-34 modulates the functions of MOs/MФs via BpCSF-1R1.

8.
Xenobiotica ; : 1-6, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32150479

RESUMO

Apatinib, a small molecule anti-angiogenic tyrosine kinase inhibitor is used extensively to treat advanced gastric cancer and simvastatin (SV) is often co-prescribed to treat cardiovascular disease in cancer patients. As both apatinib and SV are metabolized primarily by cytochrome P450 variant CYP3A4, they are likely to interact. Therefore, the potential effect of SV co-administration on pharmacokinetics of apatinib in Sprague-Dawley male rats is demonstrated for the first time.Sixteen rats were randomly divided into two groups (n = 8), 2 mg/kg SV orally co-administrated for seven days (group B) and the corresponding control group (group A). Apatinib concentrations of rat plasma samples were detected by ultra-performance liquid chromatography tandem mass spectrometry. Pharmacokinetic parameters were calculated using non compartmental methods.Co-administration of SV for seven days significantly increased area under curve (AUC(0-t)), AUC(0-∞) and maximum plasma concentration of apatinib by 2.4-, 2.4-, and 2.7-fold, respectively while decreasing apparent volume of distribution and clearance by 81.7 and 73.9%, respectively.These findings suggest that concomitant administration of SV with 7 days may have inhibited the metabolism of apatinib in rats.

9.
Sci Total Environ ; 719: 137404, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32120098

RESUMO

Housing inequality, where the wealthy hold much more housing than those 5 less so, is common worldwide, but how it correlates with haze pollution and hence air pollution has not been studied to date. Due to the market-oriented and finance-driven evolution of its housing system over the last two decades, housing inequality is particularly prominent in post-reform urban China while air pollution has become an increasingly serious problem too. This study explores the relationship between housing inequality and air pollution using 2002-2009 spatial panel data of 65 Chinese cities, to find that housing inequality contributes to exacerbating air pollution. It is also shown that an excessive demand for real estate development due to the uneven distribution of the housing stock is an important mechanism underlying the correlation between housing inequality and air pollution. In addition, such factors as economic development, city size, urbanization level, industrial structure, and capital stock all have different degrees of impact on the correlation between housing inequality and air pollution. The paper concludes by discussing the policy implications of this research and offering some policy recommendations.

10.
Microbiol Res ; 236: 126443, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32146293

RESUMO

Recently, the characteristics of prevalent bacterial pathogens causing bovine mastitis have become increasingly complicated, and many commensal or unusual bacterial species have been isolated from milk samples of cows with mastitis. Strain JS20170427COW was isolated dominantly from the milk of Holstein Friesian cows with mastitis in Jiangsu province in China. Colonies of this strain showed a hillock-like protrusion, with a pale-yellow color at the protrusion and a transparent edge, 4-5 mm in diameter after cultivation at 37 °C for 24 h on 5% sheep blood-enriched agar. Although 16 s rRNA analysis showed the closest relationship with the family Flavobacteriaceae containing Elizabethkingia spp., Riemerella sp. and Soonwooa buanensis, the bacterial species of strain JS20170427COW could not be identified adequately because it had a sequence identity of less than 95 % in 16 s rRNA when compared with all the known species of the family Flavobacteriaceae. Unexpectedly, both the first and re-sequencing data determined the whole genome size of strain JS20170427COW to be 2.69 Mb, which is different from the above three closest bacterial species. Therefore, we hypothesized that strain JS20170427COW is a novel taxon of Flavobacteriaceae. Further identification using conserved genes, single-nucleotide polymorphisms (SNPs), phylogenetic and average nucleotide identity analyses based on whole genome data suggested that JS20170427COW was more likely to be an Elizabethkingia-like strain, but that it does not belong to the Elizabethkingia genus. Comparison of the predicted open reading frames (ORFs) revealed that strain JS20170427COW encodes more special genes than Elizabethkingia species. In summary, we identified a novel Flavobacteriaceae taxon showing a close relationship with Elizabethkingia subspecies, which has potential pathogenicity in bovine mastitis.

11.
Sci Data ; 7(1): 90, 2020 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-32165614

RESUMO

Turbot (Scophthalmus maximus) is a commercially important flatfish species in aquaculture. It has a drastic sexual dimorphism, with females growing faster than males. In the present study, we sequenced and de novo assembled female and male turbot genomes. The assembled female genome was 568 Mb (scaffold N50, 6.2 Mb, BUSCO 97.4%), and the male genome was 584 Mb (scaffold N50, 5.9 Mb, BUSCO 96.6%). Using two genetic maps, we anchored female scaffolds representing 535 Mb onto 22 chromosomes. Annotation of the female anchored genome identified 87.8 Mb transposon elements and 20,134 genes. We identified 17,936 gene families, of which 369 gene families were flatfish specific. Phylogenetic analysis showed that the turbot, Japanese flounder and Chinese tongue sole form a clade that diverged from other teleosts approximately 78 Mya. This report of female and male turbot draft genomes and annotated genes provides a new resource for identifying sex determination genes, elucidating the evolution of adaptive traits in flatfish and developing genetic techniques to increase the sustainability of turbot aquaculture.


Assuntos
Linguados/genética , Genoma , Animais , Evolução Molecular , Feminino , Masculino , Anotação de Sequência Molecular , Filogenia , Fatores Sexuais
12.
Biomed Pharmacother ; 126: 110048, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32145587

RESUMO

Disulfiram (DSF) is an FDA approved anti-alcoholism drug in use for more than 60 years. Recently, antitumor activity of the DSF/copper (DSF/Cu) complex has been identified. Its anti-multiple myeloma activity, however, has barely been investigated. In the present study, our results demonstrated that the DSF/Cu complex induced apoptosis of MM cells and MM primary cells. The results indicated that DSF/Cu significantly induced cell cycle arrest at the G2/M phase in MM.1S and RPMI8226 cells. Moreover, JC-1 and Western blot results showed that DSF/Cu disrupted mitochondrial membrane integrity and cleaved caspase-8 in MM cells, respectively, suggesting that it induced activation of extrinsic and intrinsic apoptosis pathways. Interestingly, DSF/Cu induced caspase-3 activation was partly blocked by Z-VAD-FMK (zVAD), a pan-caspase inhibitor, indicating at caspase-dependent and -independent paths involved in DSF/Cu induced myeloma cell apoptosis machinery. Additionally, activation of the c-Jun N-terminal kinase (JNK) signaling pathway was observed in DSF/Cu treated MM cells. More importantly, our results demonstrated that DSF/Cu significantly reduced tumor volumes and prolonged overall survival of MM bearing mice when compared with the controls. Taken together, our novel findings showed that DSF/Cu has potent anti-myeloma activity in vitro and in vivo highlighting valuable clinical potential of DSF/Cu in MM treatment.

13.
J Med Chem ; 63(6): 3370-3380, 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32115956

RESUMO

To validate PDE4 inhibitors as novel therapeutic agents against vascular dementia (VaD), 25 derivatives were discovered from the natural inhibitor α-mangostin (IC50 = 1.31 µM). Hit-to-lead optimization identified a novel and selective PDE4 inhibitor 4e (IC50 = 17 nM), which adopted a different binding pattern from PDE4 inhibitors roflumilast and rolipram. Oral administration of 4e at a dose of 10 mg/kg exhibited remarkable therapeutic effects in a VaD model and did not cause emesis to beagle dogs, indicating its potential as a novel anti-VaD agent.

14.
Food Funct ; 11(3): 2693-2703, 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32182310

RESUMO

Broadly, bok-choy is known for its potential benefits as part of a human diet. However, the effects and deeper investigations of bok-choy on human health are still insufficient. This study aimed to investigate the beneficial effects of two cultivars of bok-choy, 'Suzhouqing' (green cultivar) and 'Ziluolan' (purple cultivar), on growth performance, lipid metabolism and related gene expressions in Syrian golden hamsters. Fifty six male Syrian golden hamsters (6-months-old) were randomly assigned into 6 groups: normal diet (A), high-fat diet (B), high-fat diet + 5% 'Suzhouqing' (C), high-fat diet + 7% 'Suzhouqing' (D), high-fat diet + 5% 'Ziluolan' (E), and high-fat diet + 7% 'Ziluolan' (F), fed for 56 consecutive days. On day 0, 28 and 56, blood and liver samples were collected to examine the lipid profile, liver enzymes, histomorphology and related gene expressions. The results showed that group B had significantly increased levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase, while (P < 0.05) showed impaired levels of high-density lipoprotein cholesterol compared with group A. Group D, E and F had significantly reduced levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase, while the level of high-density lipoprotein cholesterol was significantly increased compared with group B. Remarkably, the mRNA expressions of CEBP-α, DGAT1, lipoprotein lipase (LPL), FASN and 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA) were significantly up-regulated and carnitine palmitoyl transferase 2 (CPT2), Cyp27A1 and proliferator activated receptor alpha (PPAR-α) were significantly down-regulated in group B compared with group A. However, in group D, E and F, the mRNA expression levels of CCAAT enhancer binding protein alpha, DGAT1, LPL, FASN and HMG-CoA were significantly down-regulated and CPT2, Cyp27A1 and PPAR-α were significantly up-regulated compared with group B. In conclusion, different amounts of bok-choy added to the diets incredibly improved the lipid-profile, enhanced liver enzyme activities and related gene expression. The hamsters supplemented with 7% 'Ziluolan' exhibited the best performance among all the other high-fat groups, which shows that Ziluolan could be a great alternative for the reduction of fat accumulation and conserving health.

15.
Oncotarget ; 11(7): 755-757, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32133049

RESUMO

[This corrects the article DOI: 10.18632/oncotarget.4708.].

16.
Sci Total Environ ; 714: 136731, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32018959

RESUMO

Green logistics policies (GLP) are essential to the progress of green logistics, the promotion of green growth, and the fulfillment of sustainable development. However, as the uncertainty and ambiguity of factors that influence the implementation of GLP, it is urgent to explore and reveal the antecedents and functional mechanism of the effectiveness of GLP. This study adopts grounded theory method to conduct in-depth interviews, and concludes that five major factors, such as the perfection of GLP system, the green governance capacity of government, the level of perception of logistics enterprises on GLP, the level of social supervision, and the development level of logistics industry, which influence the effectiveness of GLP. And then presents the integrated model of antecedents of the effectiveness of GLP, revealing the influence path and internal mechanism of these influencing factors. It is of great significance to enhancing the effectiveness of GLP, upgrading green logistics, and achieving the green development.

17.
Yonsei Med J ; 61(3): 210-217, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32102121

RESUMO

PURPOSE: The goal of this study was to explore the effects of hsa-let-7g on cell proliferation and apoptosis, and elucidate its role in lung cancer development. MATERIALS AND METHODS: The expression levels of has-let-7g and HOXB1 in tissues and cells were measured by qRT-PCR. An inhibitor of hsa-let-7g or one targeting a control messenger RNA were transfected into A549 and H1944 lung cancer cells, and the effects of hsa-let-7g dysregulation on cell viability and apoptosis were analyzed using CCK-8 and apoptosis detection assays. HOXB1 was confirmed as the target gene of hsa-let-7g, based on luciferase reporter assay results. The relationship between hsa-let-7g and HOXB1 was confirmed by co-transfection of inhibitors of hsa-let-7g and HOXB1 followed by Western blot, CCK-8, and apoptosis detection assays. RESULTS: We observed high expression of hsa-let-7g in lung cancer tissues compared to the corresponding normal tissues, and generally higher expression of hsa-let-7g in patients with advanced tumor classification. The results of CCK-8 and apoptosis detection experiments showed that the inhibition of hsa-let-7g significantly inhibited proliferation of A549 and H1944 cells, but also promoted apoptosis. HOXB1 is a specific target of hsa-let-7g, and downregulation of HOXB1 in lung cancer cells reversed the suppressive effects caused by knocking down hsa-let-7g. CONCLUSION: These data collectively suggest that the expression of hsa-let-7g inhibits lung cancer cells apoptosis and promotes proliferation by down-regulating HOXB1. The results from this study demonstrate the potential of hsa-let-7g/HOXB1 axis as a therapeutic target for the treatment of lung cancer.

18.
J Ethnopharmacol ; 252: 112618, 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-32006632

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Sini decoction (SND) is a famous Traditional Chinese Medicine (TCM) formula composed of Acontium carmichaeli, Zingiber officinale and Glycyrrhiza uralensis, which is considered as an efficient formula against doxorubicin (DOX)-induced heart failure. But the compatibility mechanism of SND remains unclear. AIM OF THE STUDY: The present study aimed to investigate the compatibility mechanism of SND against DOX-induced heart failure in rats. MATERIALS AND METHODS: Mass spectrometry-based serum metabolomics were performed. The relative distance values (RDVs) of SND, A. carmichaeli-free decoction (ACFD), Z. officinale-free decoction (ZOFD) and G. uralensis-free decoction (GUFD) treated groups from the control/DOX groups in multidimensional space were calculated to provide a measure of compatibility effect of SND. SND, ACFD, ZOFD, GUFD-targeted metabolic pathways were identified and compared to investigate the synergistic mechanism of SND by computational systems analysis. Real-time quantitative PCR was further employed to validate the key metabolic pathways at the level of the gene. RESULTS: The RDVs combined with the hemodynamic and biochemical analysis showed that the protection effects were sorted as SND > GUFD > ZOFD > ACFD. It revealed that DOX-induced heart failure perturbed 16 metabolic pathways, and SND, GUFD, ZOFD and ACFD-treated groups could significantly reversed 12, 10, 7 and 6 metabolic pathways of these 16 metabolic pathways, respectively. Metabolic pathway and RT-PCR analysis indicated that both SND and GUFD could protect DOX-induced heart failure mainly by regulating PLA2-COX pathway and PLA2-CYP pathway. CONCLUSION: It can be concluded that A. carmichaeli played an essential role in attenuation of DOX-induced heart failure among the three herb constituents of SND and the constituent herbs mutually reinforced each other. This work demonstrated that metabolomics combined with computational systems analysis was a promising tool for uncovering the compatibility effects of TCM.

19.
Inflamm Bowel Dis ; 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32105310

RESUMO

BACKGROUND: CALM was a randomized phase 3 trial in patients with Crohn's disease (CD) that demonstrated improved endoscopic outcomes when treatment was escalated based on cutoffs for inflammatory biomarkers, fecal calprotectin (FC), C-reactive protein (CRP), and CD Activity Index (CDAI) remission vs CDAI response alone. The purpose of this post hoc analysis of CALM was to identify drivers of treatment escalation and evaluate the association between biomarker cutoff concentrations and endoscopic end points. METHODS: The proportion of patients achieving CD Endoscopic Index of Severity (CDEIS) <4 and no deep ulcers 48 weeks after randomization was evaluated according to CRP <5 mg/L or ≥5 mg/L and FC <250 µg/g or ≥250 µg/g. Subgroup analyses were performed according to disease location, and sensitivity analyses were conducted in patients with elevated CRP and/or FC at baseline. The association between endoscopic end points and biomarker cutoffs was performed using χ 2 test. RESULTS: The proportion of patients who achieved the primary end point CDEIS <4 and no deep ulcers was significantly greater for those with FC <250 µg/g (74%; P < 0.001), with an additive effect for CRP <5 mg/L. The association of FC <250 µg/g with improved endoscopic outcomes was independent of disease location, although the greatest association was observed for ileocolonic disease. Fecal calprotectin <250 µg/g, CRP <5 mg/L, and CDAI <150 gave a sensitivity/specificity of 72%/63% and positive/negative predictive values of 86%/42% for CDEIS <4 and no deep ulcers 48 weeks after randomization. CONCLUSION: This post hoc analysis of CALM demonstrated that a cutoff of FC <250 µg/g is a useful surrogate marker for mucosal healing in CD.

20.
mSphere ; 5(1)2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-32075882

RESUMO

Intrapartum antibiotic prophylaxis reduces the risk of infection to a mother and neonate, but antibiotic-mediated maternal and neonatal microbiota dysbiosis increases other health risks to newborn infants. We studied the impact of perinatal antibiotic prophylaxis on the microbiota in mothers and newborns with full-term or preterm delivery. Ninety-eight pregnant women and their neonates were divided into the following four groups: full term without antibiotic exposure (FT), full term with antibiotic exposure (FTA), preterm without antibiotic exposure (PT), and preterm with antibiotic exposure (PTA). Bacterial composition was analyzed by sequencing the 16S rRNA gene from maternal vaginal swabs (V) and neonatal meconium (F). The results showed that in maternal vaginal and neonatal meconium microbiota, FT and PT groups had a higher load of Lactobacillus spp. than did the FTA and PTA groups. In addition, whether in the mother or newborn, the dissimilarity in microbiota between FT and PT was the lowest compared to that between other groups. Compared to the FT and PT groups, the dissimilarity in microbial structures between the vagina and meconium decreased in the FTA and PTA groups. The health outcome of infants reveals an association between early-onset sepsis and antibiotic-mediated microbiota dysbiosis. In conclusion, perinatal antibiotic exposure is related to the establishment of gut microbiota and health risks in newborns. Promoting the rational usage of antibiotics with pregnant women will improve neonatal health.IMPORTANCE Perinatal antibiotic prophylaxis is an effective method for preventing group B Streptococcus (GBS) infection in newborns. Antibiotic exposure unbalances women's vaginal microbiota, which is associated with the establishment of the newborn gut microbiota. However, the influence of perinatal antibiotic exposure on neonatal gut microbiota colonization and health outcomes remains unclear. In this study, we found that perinatal antibiotic exposure induced microbiota dysbiosis in a woman's vagina and the neonatal gut, and we highlight a significant decrease in the abundance of Lactobacillus spp. The influence of antibiotic use on the microbiota was greater than that from gestational age. Additionally, full-term newborns without antibiotic exposure had no evidence of early-onset sepsis, whereas in full-term or preterm newborns with antibiotic exposure before birth, at least one infant was diagnosed with early-onset sepsis. These results suggest an association between perinatal antibiotic exposure and microbial dysbiosis in maternal vaginal and neonatal gut environments, which may be related to the occurrence of early-onset sepsis.

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