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1.
Biomed Pharmacother ; 121: 109603, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31707339

RESUMO

Accidental phosgene exposure can result in acute lung injury (ALI). Mesenchymal stem cells (MSCs) have been found to alleviate phosgene-induced ALI. However, the mechanism of MSCs underlying such protective effect remains largely unexplored. Exosomes, important components of microenvironment, are closely associated with intercellular information transfer. In the present study, we isolated lung exosomes in rats after phosgene exposure by ultracentrifugation and explored their effects on MSCs in vitro. ALI exosomes were elliptical in shape and 50-200 nm in size. ALI exosomes could promote proliferation and migration of MSCs. Moreover, ALI exosomes increased the secretion of IL-10, leading to enhanced immunoregulatory properties of MSCs. The paracrine factors, VEGF, HGF, LL-37 and Ang-1, were also augmented by ALI exosomes. However, ALI exosomes had no effect on differentiation of MSCs towards lung alveolar cells. To identify the effective miRNAs in ALI exosomes, we performed miRNA profile analysis. MiR-28-5p was considered as a possible effective molecule. We further studied the effect of miR-28-5p on MSCs. MiR-28-5p mimic promoted proliferation, migration, immunomodulation of MSCs. MiR-28-5p mimic promoted the paracrine of VEGF, HGF, LL-37 and Ang-1. Besides, we explored molecular mechanism of miR-28-5p in MSCs. PI3K/Akt signaling pathway was found significantly augmented by miR-28-5p mimic, indicating the activation in this process. Taken together, our findings could help identify the effects of lung-derived exosomes on MSCs, and the effective molecule in exosomes, miR-28-5p, activated MSCs through PI3K/Akt signaling pathway.

2.
J Cell Biochem ; 121(1): 231-243, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31190401

RESUMO

The significance of actin-related protein 2/3 complex subunit 4 (ARPC4) expression in bladder cancer, and its potential role in the invasion and migration of bladder cancer cells, has yet to be determined. This study was to identify the correlation between ARPC4 and lymph node metastasis, and to determine the role of ARPC4 in the invasive migration of T24 bladder cancer cells. One hundred and ninety-eight bladder cancer tissues and 40 normal bladder and lymph node tissues were examined. Tissue microarrays were constructed and subjected to immunohistochemical stating for ARPC4. Multiple logistic analysis was used to determine risk factors associated with bladder cancer metastasis. ARPC4 expression in T24 bladder cancer cells was suppressed using small interfering RNA and changes in protein levels were determined by Western blot analysis. The proliferation of bladder cancer cells after knocking down of ARPC4 was determined by cell counting kit-8. The effects of ARPC4 knockdown on T24 cell invasion and migration was determined using transwell and wound healing assays. Immunofluorescence analysis was performed to examine changes in pseudopodia formation and actin cytoskeleton structure. The expression of ARPC4 was elevated in bladder cancer tissues than normal tissues (84.3% vs 27.5%, P < 0.001). The multivariate logistic analysis demonstrated that the level of ARPC4, as a risk factor, was correlated with lymphatic metastasis (P < 0.05). ARPC4 knockdown attenuated proliferation, migration, invasion, and pseudopodia formation in T24 cells. ARPC4 expression, as a risk factor, is associated with lymphatic metastasis and is upregulated in bladder cancer tissues in comparison with normal tissues. Inhibition of ARPC4 expression significantly attenuates the proliferation, migration, and invasion of bladder cancer cell, possibly due to defects in pseudopodia formation.

3.
J Clin Lab Anal ; : e23136, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31793719

RESUMO

BACKGROUND: The oncogene a disintegrin and metalloproteinase 9 (ADAM9) was up-regulated in ovarian cancer tissues, and the present study aims to explore the potential diagnostic and prognostic value of ADAM9 in ovarian cancer (OC). METHODS: A total of 30 paired fresh OC tumor tissues and the paired-adjacent normal tissue, and 90 formalin-fixed paraffin-embedded (FFPE) OC samples and adjacent normal tissue were collected. The expression of OC in FFPE samples was examined by immunohistochemical methods, and the mRNA expression of ADAM9 in fresh tumor samples was examined by RT-qPCR methods. Receiver operating characteristics curve was drawn to analyze the potential diagnostic value of ADAM9. Kaplan-Meier survival analysis was performed to compare the overall survival (OS) and disease-free survival (DFS) of the ADAM9 positive and negative OC patients. RESULTS: The positive rate of ADAM9 in FFPE OC tumor tissue was markedly higher than in the non-tumorous tissue (61/90 vs 47/90), and increased expression level of ADAM9 may associate with higher histological grade, advanced Figo stage and increased risk of metastasis; moreover, the mRNA expression of ADAM9 was also increased in OC tissue compared with the normal tissue (P < .001), and results of ROC analysis suggested that ADAM9 is a sensitive marker for the diagnosis of OC( AUC 0.8389, 95% confidence interval 0.7333 to 0.9445); finally, increased expression of ADAM9 may indicate decreased OS (P = .004) and DFS (P = .014) of the patients. CONCLUSION: A disintegrin and metalloproteinase 9 was up-regulated in OC, and ADAM9 may serve as potential diagnostic and prognostic marker for the diagnosis and treatment of OC.

4.
ISA Trans ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31796209

RESUMO

In this technical note, we present an adaptive fuzzy hierarchical sliding mode control method to deal with the control problem of under-actuated switched nonlinear systems. For the system under consideration, both the issues of unknown uncertain functions and aperiodically updating input are taken into account, which are of practical importance. A bounded time-varying function is employed to make a linear transformation of the control input, leading to a transformed system that can be applied to the control design. By introducing the so-called hierarchical structure, a top layer hierarchical sliding surface containing all the system states' information is obtained. Furthermore, by carrying out fuzzy logic systems' universal approximation, the problem caused by unknown system uncertainties is tackled. The approximation errors together with the measurement error resulted from the effects of the triggering event are lumped into a function, and its upper bound is estimated on-line. Based on these, the boundedness of all the signals are verified by combining the Lyapunov theory and projection algorithm. To testify the validity of our control scheme, a simulation example is carried out.

5.
Mol Genet Genomic Med ; : e1032, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31701684

RESUMO

BACKGROUND: The aim of this study was to generate a prognostic model to predict survival outcome in pediatric Wilms tumor (WT). METHODS: The data including mRNA expression and clinical information of pediatric WT patients were downloaded from the Therapeutically Available Research to Generate Effective Treatments (TARGET) database. The differentially expressed genes were identified and a prognostic signature of pediatric WT was generated according to the results of univariate and multivariate Cox analysis. Receiver operating characteristic (ROC) curve was used to evaluate the five-mRNA signature in pediatric Wilms tumor patients. Bootstrap test with 500 times was used to perform the internal validation. RESULTS: We identified 6,964 differentially expressed mRNAs associated with pediatric WT, including 3,190 downregulated mRNAs and 3,774 up-regulated mRNAs. Univariate and multivariate Cox analysis identified five mRNAs (SPRY1, SPIN4, MAP7D3, C10orf71, and SPAG11A) to establish a predictive model. The risk score formula is as follows: Risk score = 0.3036*SPIN4 + 0.8576*MAP7D3 -0.1548*C10orf71 -0.7335*SPRY1 -0.2654*SPAG11A. The pediatric WT patients were divided into low-risk group and high-risk group based on the median risk score (value = 1.1503). The receiver operating characteristic (ROC) curve analysis revealed good performance of the 5-mRNA prognostic model (the area under the curve [AUC] was 0.821). Bootstrap test (Bootstrap resampling times = 500) was used to perform the internal validation and revealed that the AUC was 0.822. REACTOME, KEGG, and BIOCARTA pathway analyses demonstrated that these survival-related genes were mainly enriched in ErbB2 and ErbB3 signaling pathways, and calcium signaling pathway. CONCLUSION: The five-mRNA signature can predict the prognosis of patients with pediatric WT. It has significant implication in the understanding of therapeutic targets for pediatric WT patients. However, further study is needed to validate this five-mRNA signature and uncover more novel diagnostic or prognostic mRNAs candidates in pediatric WT patients.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31702495

RESUMO

BACKGROUND: Previous clinical studies have suggested that apolipoprotein M (apoM) is involved in glucose metabolism and play a causative role in insulin sensitivity. OBJECTIVE: We aimed to explore the potential mechanism of apoM on modulating glucose homeostasis and analyze differentially expressed genes by employing ApoM deficient (ApoM-/-) and wild type (WT) mice. METHOD: The metabolism of glucose in the hepatic tissues of high-fat diet ApoM-/- and WT mice was measured by a glycomics approach. Bioinformatic analysis was applied for analyzing the levels of differentially expressed mRNAs in the liver tissues of these mice. The insulin sensitivity of ApoM-/- and WT mice was compared using insulin tolerance test and the phosphorylation levels of protein kinase Akt (AKT) following insulin stimulation in different tissues were examined by Western blot. RESULTS: The majority of the hepatic glucose metabolites exhibited lower concentration levels in the ApoM-/- mice compared with those of the WT mice. Gene Ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that ApoM deficiency affected the genes associated with the metabolism of glucose. The insulin tolerance test suggested that insulin sensitivity was impaired in ApoM-/- mice. The phosphorylation levels of AKT in muscle and adipose tissues of ApoM-/- mice were significantly diminished in response to insulin stimulation compared with those noted in WT mice. CONCLUSION: ApoM deficiency led to the disorders of glucose metabolism and altered glucose metabolism related genes in mice liver. In vivo data indicated that apoM might augment insulin sensitivity by AKT-dependent mechanism.

7.
J Burn Care Res ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31720689

RESUMO

An important feature of acute respiratory distress syndrome (ARDS) is fluid lost into the interstitium of lung combined with its compromised reabsorption, resulting in the elevation of extravascular lung water (EVLW). Although ARDS is known as an early, common, and life-threatening complication in major burns, the issue of whether or how the EVLW index (EVLWI) correlates to its prognosis has not been identified yet. In this retrospectively study, 121 severely burned adults with ARDS occurred in two weeks postburn were analyzed and divided into two groups: survivors (73 patients) and non-survivors (48 patients) according to the 28-day outcome after injury. Compared to non-survivors, survivors exhibited bigger EVLWI reduction in day 2 after ARDS onset (ΔEVLWI2), with no differences in ARDS timing and other EVLWI variables. ΔEVLWI2, rather than EVLWI on 2 days after ARDS onset, was identified as an independent prognostic factor even after adjusting other significant factors by Cox proportional hazard analysis. ROC curve analysis showed that ΔEVLWI2 [AUC=0.723, 95% CI= (0.631- 0.816), P<0.001] was a relative predictor for survival on 28-day postburn, with a threshold of 1.9 ml/kg (63.0% sensitivity, 77.1% specificity). Kaplan-Meier survival curve analysis confirmed a significantly higher survival rate on 28-day postburn in patients with ΔEVLWI2 > 1.9 ml/kg (log-rank test: χ2 =14.780, P< 0.001). Taken together, our study demonstrated that ΔEVLWI2 is an independent prognostic factor for early ARDS in severe burns. ΔEVLWI2 higher than 1.9 ml/kg might predict a higher survival rate in those patients.

8.
Zootaxa ; 4624(4): zootaxa.4624.4.7, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31716201

RESUMO

A new species of the microhylid frog genus Microhyla is described from the Fanjing Mountain of Guizhou Province, China. Phylogenetic analyses based on DNA sequences of the the mitochondrial 12S rRNA, 16S rRNA and COI genes supported the new species as an independent lineage, closely related to M. beilunensis, M. mixtura and M. okinavensis. The uncorrected genetic distance on 16S rRNA gene between the new species and its closest congeners M. beilunensis, M. mixtura and M. okinavensis are 3.5%, 4.6% and 4.6% respectively. The new species is distinguished from its congeners by a combination of the following morphological characters: (1) body of medium size (SVL 19.0-22.7 mm in males and 22.5-23.0 mm in females); (2) disk and dorsal median longitudinal groove on finger tips absent; (3) toe with rudimentary webbing at base; (4) disk with dorsal median longitudinal groove present at toe tips except for the toe I; (5) two metatarsal tubercles on palm; (6) tibiotarsal articulation reaching the level between eye to nostril when leg stretched forward; (7) a distinct V-shaped white stripe on the upper midsection. The new species is known only from the type locality, and thus the finding of it has contributed to the endemic species diversity of China. It is needed to take strategy to protect the species and habitats due to the increased threats of environmental changes.


Assuntos
Anuros , Animais , Tamanho Corporal , China , Feminino , Masculino , Filogenia , RNA Ribossômico 16S
9.
World J Microbiol Biotechnol ; 35(12): 192, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31773365

RESUMO

Corynebacterium glutamicum is generally regarded as a safe microorganism, and widely used in the large-scale production of various amino acids and organic acids, such as L-glutamate, L-lysine and succinic acid. During the process of industrial fermentation, C. glutamicum is usually exposed to varying environmental stresses, such as variations in pH, salinity, temperature, and osmolality. Among them, pH fluctuations are regarded as one of the most frequent environmental stresses in microbial fermentation. In this review, we summarize the current knowledge of pH homeostasis mechanisms adopted by C. glutamicum for coping with low acidic pH and high alkaline pH stresses. Facing with low pH environments, C. glutamicum develops a variety of strategies to maintain intracellular pH homeostasis, such as lowering intracellular reactive oxygen species, the improvement of potassium transport, the regulation of mycothiol-related pathways, as well as the repression of sulfur assimilation. While during alkaline pH stresses, the Mrp-type Na+/H+ antiporters are shown to play a dominant role in conferring C. glutamicum cells resistance to alkaline pH. Furthermore, we also discuss the general strategies and prospects on metabolic engineering of C. glutamicum to improve alkaline or acid resistance.

10.
J Am Chem Soc ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31774664

RESUMO

The occurrence and development in early pathological stage of pancreatic cancer had been proved to be associated with mi-croRNAs. However, it remains a great challenge to monitor low-expression and even down-regulation microRNA among living cells, tissues and serum samples, directly. In this work, Staudinger reduction is firstly applied in intracellular mi-croRNA detection, establishing a set of smart hybridization-mediated Staudinger reduction probe (HMSR-probe) which containing designed oligonucleotide sequences. Meanwhile, 40 serum samples of healthy people (6), patients with pancreati-tis (22) and pancreatic cancer patients (12) are tested for exploring the potential clinical application. Of note, the molecules bound to nucleic acid confine reactive site into close proximity in a compact space, and non-connected product from Staudinger reaction facilitate turnover amplification to get ameliorative detection limit (1.3 × 10-15 M). Moreover, comparing with qRT-PCR, low false positive signal and excellent specificity makes the probe more suitable and convenient for pancre-atic cancer diagnosis in blood samples. For practical application, HMSR-probe enable accurate differentiation in cell and tissue samples under both 488 nm and 785 nm, and it get good coherence to known research. As a proof of concept, the reli-able results in distinguishing pancreatic cancer patients from different morbid stages might supply a feasible method for en-dogenous microRNA detection in fundamental research and clinical diagnostics.

11.
Target Oncol ; 14(6): 719-728, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31691892

RESUMO

BACKGROUND: Droplet digital polymerase chain reaction (ddPCR) is an emerging technology for quantitative cell-free DNA oncology applications. However, a ddPCR assay for the epidermal growth factor receptor (EGFR) p.Thr790Met (T790M) mutation suitable for clinical use remains to be established with analytical and clinical validations. OBJECTIVE: We aimed to develop and validate a new ddPCR assay to quantify the T790M mutation in plasma for monitoring and predicting the progression of advanced non-small-cell lung cancer (NSCLC). METHODS: Specificity of the ddPCR assay was evaluated with genomic DNA samples from healthy individuals. The inter- and intraday variations of the assay were evaluated using mixtures of plasmid DNA containing wild-type EGFR and T790M mutation sequences. We assessed the clinical utility of the T790M assay in a multicenter prospective study in patients with advanced NSCLC receiving tyrosine kinase inhibitor (TKI) treatment by analyzing longitudinal plasma DNA samples. RESULTS: We set the criteria for a positive call when the following conditions were satisfied: (1) T790M mutation frequency > 0.098% (3 standard deviations above the background signal); (2) at least two positive droplets in duplicate ddPCR reactions. Among the 62 patients with advanced NSCLC exhibiting resistance to TKI treatment, 15 had one or more serial plasma samples that tested positive for T790M. T790M mutation was detected in the plasma as early as 205 days (median 95 days) before disease progression, determined by imaging analysis. Plasma T790M concentrations also correlated with intervention after disease progression. CONCLUSIONS: We developed a ddPCR assay to quantify the T790M mutation in plasma. Quantification of longitudinal plasma T790M mutation may allow noninvasive assessment of drug resistance and guide follow-up treatment in TKI-treated patients with NSCLC. TRIAL REGISTRATION: Clinical Trials.gov identifier: NCT02804100.

12.
J Endod ; 45(12): 1543-1549, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31676043

RESUMO

The palatogingival groove is a developmental anomaly that typically starts near the cingulum of the maxillary incisors and extends along the roots at varying lengths and depths. Severe grooves that extend to the root apex often lead to complex combined periodontal-endodontic lesions. There are various therapeutic options available for these cases; however, the prognosis is unfavorable. Here, we report the successful surgical treatment of 3 cases of maxillary lateral incisors with severe palatogingival grooves using intentional replantation with a 2-segment restoration method. The teeth were gently extracted, resulting in minimal damage to the periodontal ligament. Under a dental operating microscope, 3 mm of the root end was resected. The palatogingival groove was removed, and root-end preparation was performed with a #700 fissure bur. The groove cavity was connected with root-end cavity to form a class II cavity. The cavity was then filled using a 2-segment restoration method (ie, dividing the cavity into 2 parts by the cementoenamel junction, the coronal portion was filled with a flowable composite while the radicular portion, including the root-end cavity, was filled with bioceramics). The tooth was then replanted into its alveolar bone and splinted with a flexible splint for 7 days. The sinus tract was closed at the 1-week postoperative visit. During subsequent recalls, the teeth showed almost complete periapical healing. In summary, intentional replantation with a 2-segment restoration method is a viable treatment modality for single-rooted teeth with a severe palatogingival groove that extends to the root apex.

13.
Aging (Albany NY) ; 11(21): 9478-9491, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672930

RESUMO

BACKGROUND: Numerous patients with clear cell renal cell carcinoma (ccRCC) experience drug resistance after immunotherapy. Regulatory T (Treg) cells may work as a suppressor for anti-tumor immune response. PURPOSE: We performed bioinformatics analysis to better understand the role of Treg cells in ccRCC. RESULTS: Module 10 revealed the most relevance with Treg cells. Functional annotation showed that biological processes and pathways were mainly related to activation of the immune system and the processes of immunoreaction. Four hub genes were selected: LCK, MAP4K1, SLAMF6, and RHOH. Further validation showed that the four hub genes well-distinguished tumor and normal tissues and were good prognostic biomarkers for ccRCC. CONCLUSION: The identified hub genes facilitate our knowledge of the underlying molecular mechanism of how Treg cells affect ccRCC in anti-tumor immune therapy. METHODS: The CIBERSORT algorithm was performed to evaluate tumor-infiltrating immune cells based on the Cancer Genome Atlas cohort. Weighted gene co-expression network analysis was conducted to explore the modules related to Treg cells. Gene Ontology analysis and pathway enrichment analysis were performed for functional annotation and a protein-protein interaction network was built. Samples from the International Cancer Genomics Consortium database was used as a validation set.

14.
Gene ; : 144145, 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31743769

RESUMO

Long non-coding RNA SNHG12 (lncSNHG12) plays important roles in the onset and progression of various cancers. However, the role of lncSNHG12 in osteosarcoma (OS) remains unclear. Therefore, the aim of the present study was to determine the function of lncSNHG12 in OS. A bioinformatics website was used to predict the downstream targets of lncSNHG12. In addition, qRT-PCR was employed to assess lncSNHG12 expression in OS cells. Cell migration and proliferation in vitro were verified using the transwell migration, clone formation, and CCK8 assays. Tumor metastasis and xenograft formation were monitored in nude mice with or without downregulation of lncSNHG12. The results show that lncSNHG12 was upregulated in OS cell lines. Downregulation lncSNHG12 suppressed the metastasis and proliferation both in vitro and in vivo. Also, lncSNHG12 downregulation suppressed the expression of insulin growth factor 1 receptor (IGF1R) expression through sponging miR-195-5p, which was verified with the luciferase reporter assay and rescue experiments. These findings suggest that downregulation of lncSNHG12 may suppress aggressive OS phenotypes. Moreover, lncSNHG12 silencing inhibited OS metastasis and growth by targeting the miR-195-5p/IGF1R axis, which represents a candidate marker and target for OS treatment and management.

15.
Inflamm Res ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31728561

RESUMO

OBJECTIVE: IL23R plays an important role in the pathogenesis of inflammatory bowel disease (IBD). The IL23R rs11209026 and rs10889677 polymorphisms have been shown to be associated with the development of Crohn's disease (CD) and ulcerative colitis (UC). But the results were inconsistent and inconclusive. So, we aim to investigate the genetic association between rs11209026 and rs10889677 polymorphisms and UC and CD risk by a meta-analysis. METHODS: Literature search was conducted through PubMed, CNKI, and web of science databases. Pooled OR and 95% CI was used to assess the association between the allelic, dominant and recessive models of IL23R rs11209026 and rs10889677 polymorphisms and UC and CD risk. RESULTS: 41 publications with 13,803 patients with CD and 17,446 controls, as well as 5876 patients with UC and 10,053 controls were included in the present study. All the genetic models of rs11209026 polymorphism significantly decrease CD and UC risk (except for the recessive model in UC) (p < 0.05). A subgroup analysis based on ethnicity showed that the allelic (p < 0.00001, OR = 0.65) and dominant models (p < 0.00001, OR = 0.61) of rs11209026 polymorphism were significantly associated with UC risk in Caucasians, but not in Asians (p > 0.05). In addition, the allelic (CD: p < 0.00001, OR = 1.34; UC: p < 0.00001, OR = 1.22) and dominant models (CD: p = 0.002, OR = 1.39; UC: p = 0.01, OR = 1.29), but not the recessive model of rs10889677 polymorphism significantly increase the risk of CD and UC (p > 0.05). A subgroup analysis showed that the genetic models of rs10889677 polymorphism were associated with CD risk in Caucasians (p < 0.05), but not in Asians (p > 0.05). The dominant model of rs10889677 polymorphism was associated with UC risk in Asians (p = 0.04, OR = 1.54), but not in Caucasians (p > 0.05). CONCLUSIONS: Our meta-analysis demonstrated that the rs11209026 polymorphism might be a protective factor against developing IBD, while the rs10889677 polymorphism might be a risk factor for IBD.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31657106

RESUMO

Designing effective electrocatalysts for the carbon dioxide (CO 2 ) reduction reaction (CRR) is an appealing approach to tackling the challenge posed by rising CO 2 levels and realizing a closed carbon cycle. However, CO 2 electrocatalysis still lacks a fundamental understanding owing to the complicated CRR mechanism and lack of model study systems. Herein, we have designed a model single-nickel-atom catalyst with a uniform structure and well-defined Ni-N 4 moiety on a conductive carbon support to explore the electrochemical CRR. Based on operando X-ray absorption near-edge structure spectroscopy, Raman spectroscopy and near ambient X-ray photoelectron spectroscopy investigations, Ni + in the single-nickel-atom catalyst resulting from in situ Ni 2+ reduction was found to be highly active for CO 2 activation, acting as an authentic catalytically active site for the CRR. Furthermore, through combination with a kinetics study, the rate-determining step of the CRR was determined to be *CO 2 - + H + → *COOH. This study tackles the four challenges faced by the CRR, namely, activity, selectivity, stability, and dynamics.

17.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(9): 1102-1107, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31657333

RESUMO

OBJECTIVE: To investigate the effects of fecal microbiota transplantation on septic gut flora and the cortex cholinergic anti-inflammatory pathway in rats. METHODS: Sixty clean grade male Sprague-Dawley (SD) rats were divided into normal saline (NS) control group, sepsis model group and fecal microbiota transplantation group by random number table, with 20 rats in each group. The rat model of sepsis was reproduced by injection of 10 mg/kg lipopolysaccharide (LPS) via tail vein, the rats in the NS control group was given the same amount of NS. The rats in the fecal microbiota transplantation group received nasogastric infusion of feces from healthy donor on the 1st day, 2 mL each time, for 3 times a day, the other two groups were given equal dose of NS by gavage. Fecal samples were collected on the 7th day after modeling, the levels of intestinal microbiota composition was determined using the 16SrDNA gene sequencing technology. The brain function was evaluated by electroencephalogram (EEG), and the proportion of each waveform in EEG was calculated. After sacrifice of rats, the brain tissues were harvested, the levels of protein expression of α7 nicotinic acetylcholine receptor (α7nAChR) were determined by Western Blot, and positive cells of Iba-1 in brain tissue were detected by immunohistochemistry method. The levels of interleukins (IL-6 and IL-1ß) and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Seven days after the reproduction of the model, all rats in the NS control group survived, while 10 rats and 8 rats died in the sepsis model group and fecal microbiota transplantation group, respectively, with mortality rates of 50% and 40% respectively. Finally, there were 20 rats in the NS control group, 10 in the sepsis model group and 12 in the fecal microbiota transplantation group. Compared with the NS control group, the diversity and composition of intestinal flora were changed, the incidence of abnormal EEG increased significantly, the expression of α7nAchR in the cortex decreased significantly, and the levels of Iba-1, TNF-α, IL-6 and IL-1ß were significantly increased in the model group, suggested that the intestinal flora was dysbiosis, and severe inflammatory reaction occurred in the cerebral cortex, and brain function was impaired. Compared with the model group, the diversity of intestinal flora in the fecal microbiota transplantation group was significantly increased (species index: 510.24±58.76 vs. 282.50±47.42, Chao1 index: 852.75±25.24 vs. 705.50±46.50, both P < 0.05), the dysbiosis of intestinal flora at phylum, family, genus level induced by LPS were also significantly reversed, and with the improvement of intestinal flora, the incidence of abnormal EEG waveforms was lower in the fecal microbiota transplantation group compared with that in the model group [25.0% (3/12) vs. 80.0% (8/10), P < 0.05], and the expression of α7nAChR protein in the cerebral cortex was significantly increased (α7nAChR/ß-actin: 1.56±0.05 vs. 0.82±0.07, P < 0.05), immunohistochemistry analysis showed that Iba-1 positive expression of microglia decreased significantly, and cerebral cortex TNF-α, IL-6, IL-1ß levels were significantly decreased [TNF-α (ng/L): 6.28±0.61 vs. 12.02±0.54, IL-6 (ng/L): 28.26±3.15 vs. 60.58±4.62, IL-1ß (ng/L): 33.63±3.48 vs. 72.56±2.25, all P < 0.05]. CONCLUSIONS: The results reveal that fecal microbiota transplantation has remarkably modulated the dysbiosis of intestinal microbiota and activated cholinergic anti-inflammatory pathway, and ameliorate the brain dysfunction in septic rats.


Assuntos
Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Sepse , Animais , Anti-Inflamatórios , Córtex Cerebral , Colinérgicos , Masculino , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa
18.
Biochem Biophys Res Commun ; 518(4): 752-758, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31472968

RESUMO

H2A.Z, a highly conserved histone H2A variant in eukaryotes, plays critical roles in multiple nuclear events. H2A.Z forms a heterodimer with H2B when incorporated into nucleosomes. The heterodimer dynamics has been implicated in H2A.Z functions. To gain insights into H2A.Z dynamics, we analyzed yeast H2A.Z-H2B dimer (ZB) and yeast H2A-H2B dimer (AB) using solution NMR spectroscopy. First, we measured the 1H-15N heteronuclear NOE ratio of ZB and showed that the H2A.Z αC-helix region (residues 100-118) undergoes less structure fluctuation than its H2A counterpart. Strikingly, substituting H2A residues G99N100V101 with H2A.Z counterparts R106A107 reduced the fluctuation of H2A αC-helix, suggesting that H2A.Z dynamics play an important role in αC-helix extension and H2A.Z-chaperones recognition. We next measured the hydrogen-deuterium exchange (HX) rate of ZB and verified that the H2A.Z α2 helix and H2B α2, α3 helices are mostly protected. Notably, we observed nearly identical HX profiles for dimerized ZB and AB, suggesting that they have similar solution structures and dynamic characters. Together, our study gains first insight into H2A.Z-H2B dimer dynamics and sheds light on how its dynamics affect the structure and function of H2A.Z variant.

19.
J Transl Med ; 17(1): 311, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533842

RESUMO

BACKGROUND: Prostate cancer (PCa) remains the second leading cause of deaths due to cancer in the United States in men. The aim of this study was to perform an integrative epigenetic analysis of prostate adenocarcinoma to explore the epigenetic abnormalities involved in the development and progression of prostate adenocarcinoma. The key DNA methylation-driven genes were also identified. METHODS: Methylation and RNA-seq data were downloaded for The Cancer Genome Atlas (TCGA). Methylation and gene expression data from TCGA were incorporated and analyzed using MethylMix package. Methylation data from the Gene Expression Omnibus (GEO) were assessed by R package limma to obtain differentially methylated genes. Pathway analysis was performed on genes identified by MethylMix criteria using ConsensusPathDB. Gene Ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were also applied for the identification of pathways in which DNA methylation-driven genes significantly enriched. The protein-protein interaction (PPI) network and module analysis in Cytoscape software were used to find the hub genes. Two methylation profile (GSE112047 and GSE76938) datasets were utilized to validate screened hub genes. Immunohistochemistry of these hub genes were evaluated by the Human Protein Atlas. RESULTS: A total of 553 samples in TCGA database, 32 samples in GSE112047 and 136 samples in GSE76938 were included in this study. There were a total of 266 differentially methylated genes were identified by MethylMix. Plus, a total of 369 differentially methylated genes and 594 differentially methylated genes were identified by the R package limma in GSE112047 and GSE76938, respectively. GO term enrichment analysis suggested that DNA methylation-driven genes significantly enriched in oxidation-reduction process, extracellular exosome, electron carrier activity, response to reactive oxygen species, and aldehyde dehydrogenase [NAD(P)+] activity. KEGG pathway analysis found DNA methylation-driven genes significantly enriched in five pathways including drug metabolism-cytochrome P450, phenylalanine metabolism, histidine metabolism, glutathione metabolism, and tyrosine metabolism. The validated hub genes were MAOB and RTP4. CONCLUSIONS: Methylated hub genes, including MAOB and RTP4, can be regarded as novel biomarkers for accurate PCa diagnosis and treatment. Further studies are needed to draw more attention to the roles of these hub genes in the occurrence and development of PCa.

20.
Anesthesiology ; 131(5): 1092-1109, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31517640

RESUMO

BACKGROUND: Sevoflurane administered to neonatal rats induces neurobehavioral abnormalities and epigenetic reprogramming of their germ cells; the latter can pass adverse effects of sevoflurane to future offspring. As germ cells are susceptible to reprogramming by environmental factors across the lifespan, the authors hypothesized that sevoflurane administered to adult rats could induce neurobehavioral abnormalities in future offspring, but not in the exposed rats themselves. METHODS: Sprague-Dawley rats were anesthetized with 2.1% sevoflurane for 3 h every other day between postnatal days 56 and 60. Twenty-five days later, exposed rats and nonexposed controls were mated to produce offspring. RESULTS: Adult male but not female offspring of exposed parents of either sex exhibited deficiencies in elevated plus maze (mean ± SD, offspring of both exposed parents vs. offspring of control parents, 35 ± 12 vs. 15 ± 15 s, P < 0.001) and prepulse inhibition of acoustic startle (offspring of both exposed parents vs. offspring of control parents, 46.504 ± 13.448 vs. 25.838 ± 22.866%, P = 0.009), and increased methylation and reduced expression of the potassium ion-chloride ion cotransporter KCC2 gene (Kcc2) in the hypothalamus. Kcc2 was also hypermethylated in sperm and ovary of the exposed rats. Surprisingly, exposed male rats also exhibited long-term abnormalities in functioning of the hypothalamic-pituitary-gonadal and -adrenal axes, reduced expression of hypothalamic and hippocampal Kcc2, and deficiencies in elevated plus maze (sevoflurane vs. control, 40 ± 24 vs. 25 ± 12 s, P = 0.038) and prepulse inhibition of startle (sevoflurane vs. control, 39.905 ± 21.507 vs. 29.193 ± 24.263%, P < 0.050). CONCLUSIONS: Adult sevoflurane exposure affects brain development in male offspring by epigenetically reprogramming both parental germ cells, while it induces neuroendocrine and behavioral abnormalities only in exposed males. Sex steroids may be required for mediation of the adverse effects of adult sevoflurane in exposed males.

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