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1.
Cancer Control ; 28: 10732748211041881, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34569311

RESUMO

BACKGROUND: Although Helicobacter pylori (Hp) as high risk factor for gastric cancer have been investigated from human trial, present data is inadequate to explain the effect of Hp on the changes of metabolic phenotype of gastric cancer in different stages. PURPOSE: Herein, plasma of human superficial gastritis (Hp negative and positive), early gastric cancer and advanced gastric cancer analyzed by UPLC-HDMS metabolomics can not only reveal metabolic phenotype changes in patients with gastric cancer of different degrees (30 Hp negative, 30 Hp positive, 20 early gastric cancer patients, and 10 advanced gastric cancer patients), but also auxiliarily diagnose gastric cancer. RESULTS: Combined with multivariate statistical analysis, the results represented biomarkers different from Hp negative, Hp positive, and the alterations of metabolic phenotype of gastric cancer patients. Forty-three metabolites are involved in amino acid metabolism, and lipid and fatty acid metabolism pathways in the process of cancer occurrence, especially 2 biomarkers glycerophosphocholine and neopterin, were screened in this study. Neopterin was consistently increased with gastric cancer progression and glycerophosphocholine tended to consistently decrease from Hp negative to advanced gastric cancer. CONCLUSION: This method could be used for the development of rapid targeted methods for biomarker identification and a potential diagnosis of gastric cancer.

2.
Cell Metab ; 33(10): 2059-2075.e10, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34536344

RESUMO

Myocardial ischemia-reperfusion (MIR) injury is a major cause of adverse outcomes of revascularization after myocardial infarction. To identify the fundamental regulator of reperfusion injury, we performed metabolomics profiling in plasma of individuals before and after revascularization and identified a marked accumulation of arachidonate 12-lipoxygenase (ALOX12)-dependent 12-HETE following revascularization. The potent induction of 12-HETE proceeded by reperfusion was conserved in post-MIR in mice, pigs, and monkeys. While genetic inhibition of Alox12 protected mouse hearts from reperfusion injury and remodeling, Alox12 overexpression exacerbated MIR injury. Remarkably, pharmacological inhibition of ALOX12 significantly reduced cardiac injury in mice, pigs, and monkeys. Unexpectedly, ALOX12 promotes cardiomyocyte injury beyond its enzymatic activity and production of 12-HETE but also by its suppression of AMPK activity via a direct interaction with its upstream kinase TAK1. Taken together, our study demonstrates that ALOX12 is a novel AMPK upstream regulator in the post-MIR heart and that it represents a conserved therapeutic target for the treatment of myocardial reperfusion injury.

3.
World J Gastroenterol ; 27(4): 358-370, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33584068

RESUMO

BACKGROUND: A previous study showed that irrigation with 100 mL saline reduced residual common bile duct (CBD) stones, which potentially cause recurrent stones after endoscopic retrograde cholangiopancreatography. AIM: To determine whether saline irrigation can improve CBD clearance after lithotripsy. METHODS: This prospective self-controlled study enrolled patients receiving mechanical lithotripsy for large (> 1.2 cm) CBD stones. After occlusion cholangiography confirmed CBD stone clearance, peroral cholangioscopy (POC) was performed to determine clearance scores based on the number of residual stones. The amounts of residual stones spotted via POC were graded on a 5-point scale (score 1, worst; score 5, best). Scores were documented after only stone removal (control) and after irrigation with 50 mL and 100 mL saline, respectively. The stone composition was analyzed using infrared spectroscopy. RESULTS: Between October 2018 and January 2020, 47 patients had CBD clearance scores of 2.4 ± 1.1 without saline irrigation, 3.5 ± 0.7 with 50 mL irrigation, and 4.6 ± 0.6 with 100 mL irrigation (P < 0.001). Multivariate analysis showed that CBD diameter > 15 mm [odds ratio (OR) = 0.08, 95% confidence interval (CI): 0.01-0.49; P = 0.007] and periampullary diverticula (PAD) (OR = 6.51, 95%CI: 1.08-39.21; P = 0.041) were independent risk factors for residual stones. Bilirubin pigment stones constituted the main residual stones found in patients with PAD (P = 0.004). CONCLUSION: Irrigation with 100 mL of saline may not clear all residual CBD stones after lithotripsy, especially in patients with PAD and/or a dilated (> 15 mm) CBD. Pigment residual stones are soft and commonly found in patients with PAD. Additional saline irrigation may be required to remove retained stones.


Assuntos
Cálculos Biliares , Litotripsia , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Ducto Colédoco/diagnóstico por imagem , Ducto Colédoco/cirurgia , Cálculos Biliares/diagnóstico por imagem , Cálculos Biliares/terapia , Humanos , Litotripsia/efeitos adversos , Estudos Prospectivos
4.
Ann Transl Med ; 8(20): 1295, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33209875

RESUMO

Background: In Chinese herbal medicine, Tanshinone IIA (Tan-IIA) is one of the main compounds extracted from Salvia miltiorrhiza Bunge. Tan-IIA has been demonstrated to inhibit the growth of various tumors. However, the detailed molecular and cellular mechanisms of the antitumor effect of Tan-IIA have yet to be fully illuminated. Methods: A2780 and ID-8 were treated with 0, 1.2, 2.4, 4.8, or 9.6 µg/mL Tan-IIA for 24 hours. Cell counting Kit-8 assay and EdU staining were used to evaluate cell proliferation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and flow cytometry were performed to analyze apoptosis. Western blot was carried out to determine the protein levels. Flow cytometry was used for cell cycle analysis. The levels of mRNA expression were analyzed by real-time polymerase chain reaction. The anti-tumor effect of Tan-IIA was observed in a tumor-bearing mouse model. Results: Tan-IIA inhibited the proliferation of ovarian cancer cells in a dose-dependent manner by inducing G2/M phase arrest. It also down-regulated B-cell lymphoma 2 (Bcl-2) and up-regulated Bcl-2-associated X protein (Bax) in ovarian cancer cells to induce apoptosis, and suppressed cell migration by inhibiting focal adhesion kinase phosphorylation. Tan-IIA significantly reduced vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX2) mRNA expression in ovarian cancer cells. In vivo, Tan-IIA significantly inhibited tumor growth by inducing apoptosis and promoting anti-angiogenesis. Conclusions: The results of this study shed light on the molecular and cellular mechanisms for the antitumor effect of Tan-IIA.

5.
Inorg Chem ; 59(20): 14856-14860, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-32986428

RESUMO

A flexible-robust copper(II) metal-organic framework, denoted as LIFM-100, has been successfully synthesized using a fluorinated linear dicarboxylate to link copper ions. LIFM-100 exhibits a breathing effect, which can transform reversibly between a large form (lp) and a narrow form (np) from single crystal to single crystal. In addition, LIFM-100 shows good thermal and chemical stability. By the introduction of trifluoromethyl functional groups and uncoordinated carboxyl acids, LIFM-100 features a good CO2/R22 adsorption/separation performance at 298 K, showing potential in natural gas purification and CO2/R22 capture.

6.
Chronic Dis Transl Med ; 6(3): 182-187, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32885154

RESUMO

Nephrotic syndrome is a relatively common clinical disease. Associated dyslipidemia is a risk factor for the occurrence and development of cardiovascular and renal diseases that might gradually develop into atherosclerosis, glomerulosclerosis or tubulointerstitial injury. It also confers an elevated risk of complications such as thromboembolism. If not properly controlled over the long term, dyslipidemia will become a key factor in a poor prognosis. Furthermore, dyslipidemia correlates with an increase in hepatic compensatory synthetic lipoprotein levels and a decrease in lipoprotein clearance, which can be sourced to the downregulation of hepatic and lipoprotein lipase activities in endothelial cells, muscle, and adipose tissue, and clinically characterized as hypertriglyceridemia or hypercholesterolemia. However, further investigations into the mechanism(s) of dyslipidemia are needed, with the resultant detailed perspectives and analyses substantially aiding the further development of treatment guidelines. Currently, statins represent the most popular type of pharmaceutical intervention because they lower hepatic cholesterol production and promote the absorption of low-density lipoprotein-cholesterol from the bloodstream, followed by second-line and other potential therapies to regulate the expression of specific receptors.

7.
Iran J Basic Med Sci ; 23(8): 1012-1019, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32952947

RESUMO

Objectives: To investigate and test the hypotheses that TGF-ß1 enhanced myocardial differentiation through Wnt/ß-catenin pathway with rat bone marrow mesenchymal stem cells (BMSCs). Materials and Methods: Lentiviral vectors carrying the TGF-ß1 gene were transduced into rat BMSCs firstly. Then several kinds of experimental methods were used to elucidate the related mechanisms by which TGF-ß1 adjusts myocardial differentiation in rat BMSCs. Results: Immunocytochemistry revealed that cTnI and Cx43 expressed positively in the cells that were transduced with TGF-ß1. The results of Western blot (WB) test showed that the levels of intranuclear ß-catenin and total ß-catenin were all significantly decreased. However, the cytoplasmic ß-catenin level was largely unchanged. Moreover, the levels of GSK-3ß were largely unchanged in BMSCs, whereas phosphorylated GSK-3ß was significantly decreased in BMSCs. When given the activator of Wnt/ß-catenin pathway (lithium chloride, LiCl) to BMSCs transducted with TGF-ß1, ß-catenin was increased, while phosphorylated ß-catenin was decreased. In addition, cyclinD1, MMP-7, and c-Myc protein in BMSCs transducted with Lenti-TGF-ß1-GFP were significantly lower. Conclusion: These results indicate that TGF-ß1 promotes BMSCs cardiomyogenic differentiation by promoting the phosphorylation of ß-catenin and inhibiting cyclinD1, MMP-7, and c-Myc expression in Wnt/ß-catenin signaling pathway.

8.
Chem Commun (Camb) ; 56(73): 10702-10705, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32789365

RESUMO

Triphenylimidazole-based ampholytes with intramolecular charge transfer were designed with the introduction of carboxyl groups. In solution, the synergistic solvent and ionization effects on the ampholytes led to a unique pendulum-type fluorescence variation during the water content increasing process. Among them, 4-(4,5-bis(4-hydroxyphenyl)-1H-imidazol-2-yl)benzoic acid showed the most prominent three-step fluorescence switching property.

9.
Ann Transl Med ; 8(12): 752, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32647677

RESUMO

Background: Paclitaxel is a widely used clinical first line chemotherapy drug for ovarian carcinoma. Tanshinone I (Tan-I) is one of the vital fat-soluble components, which derived from Chinese herbal medicine, Salvia miltiorrhiza Bunge. Herein, we evaluated whether Tan-I could enhance the efficacy of ovarian cancer to chemotherapy of Paclitaxel. Methods: Ovarian cancer cells A2780 and ID-8 were exposed with Tan-I (4.8 µg/mL), Paclitaxel (0.1 µg/mL), or Tan-I combination with Paclitaxel for 24 hours. The cell proliferation was analyzed by CCK8 and EdU staining. Cell apoptosis was analyzed by the TUNEL assay and flow cytometry. The protein levels were determined by western blot. Cell migration was analyzed by Transwell and wound healing. Cell senescence was analyzed by senescence-associated b-galactosidase staining. Antitumor activity was analyzed by a subcutaneous tumor xenograft model of human ovarian cancer in nude mice. The protein expression and apoptosis level of tumor tissues were analyzed by immunohistochemistry and TUNEL staining. Results: Tan-I treatment significantly elevated the Paclitaxel-cause reduction of A2780 and ID-8 cell proliferation and cell migration. Tan-I combination with Paclitaxel promotes apoptosis of cancer cells by promoting Bax expression and Bcl-2 expression. Besides, Tan-I treatment can notably increase Paclitaxel-inducing cell senescence by promoting DNA damage and senescence-associated proteins such as p21 and p16. Furthermore, the result of the transplanted tumor model indicated that Tan-I combination with Paclitaxel could inhibit tumor growth in vivo by inhibiting cell proliferation and inducing cell apoptosis. Conclusions: Natural compound Tan-I enhances the efficacy of ovarian cancer to Paclitaxel chemotherapy. The results will help to supply the potential clinical use of ovarian carcinoma cells.

10.
World J Gastroenterol ; 26(19): 2403-2415, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32476801

RESUMO

BACKGROUND: Different types of periampullary diverticulum (PAD) may differentially affect the success of endoscopic retrograde cholangiopancreatography (ERCP) cannulation, but the clinical significance of the two current PAD classifications for cannulation is limited. AIM: To verify the clinical value of our newly proposed PAD classification. METHODS: A new PAD classification (Li-Tanaka classification) was proposed at our center. All PAD patients with native papillae who underwent ERCP from January 2012 to December 2017 were classified according to three classification systems, and the effects of various types of PAD on ERCP cannulation were compared. RESULTS: A total of 3564 patients with native papillae were enrolled, including 967 (27.13%) PAD patients and 2597 (72.87%) non-PAD patients. In the Li-Tanaka classification, type I PAD patients exhibited the highest difficult cannulation rate (23.1%, P = 0.01), and type II and IV patients had the highest cannulation success rates (99.4% in type II and 99.3% in type IV, P < 0.001). In a multivariable-adjusted logistic model, the overall successful cannulation rate in PAD patients was higher than that in non-PAD patients [odds ratio (OR) = 1.87, 95% confidence interval (CI): 1.04-3037, P = 0.037]. In addition, compared to the non-PAD group, the difficulty of cannulation in the type I PAD group according to the Li-Tanaka classification was greater (OR = 2.04, 95%CI: 1.13-3.68, P = 0.004), and the successful cannulation rate was lower (OR = 0.27, 95%CI: 0.11-0.66, P < 0.001), while it was higher in the type II PAD group (OR = 4.44, 95%CI: 1.61-12.29, P < 0.01). CONCLUSION: Among the three PAD classifications, the Li-Tanaka classification has an obvious clinical advantage for ERCP cannulation, and it is helpful for evaluating potentially difficult and successful cannulation cases among different types of PAD patients.


Assuntos
Ampola Hepatopancreática/patologia , Cateterismo/métodos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Divertículo/cirurgia , Duodenopatias/cirurgia , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Ampola Hepatopancreática/cirurgia , Cateterismo/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Divertículo/diagnóstico , Divertículo/patologia , Duodenopatias/diagnóstico , Duodenopatias/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
12.
Cell Metab ; 31(5): 892-908.e11, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32375062

RESUMO

Nonalcoholic steatohepatitis (NASH) is becoming one of the leading causes of hepatocellular carcinoma (HCC). Sorafenib is the only first-line therapy for advanced HCC despite its serious adverse effects. Here, we report that at an equivalent of approximately one-tenth the clinical dose for HCC, sorafenib treatment effectively prevents the progression of NASH in both mice and monkeys without any observed significant adverse events. Mechanistically, sorafenib's benefit in NASH is independent of its canonical kinase targets in HCC, but involves the induction of mild mitochondrial uncoupling and subsequent activation of AMP-activated protein kinase (AMPK). Collectively, our findings demonstrate a previously unappreciated therapeutic effect and signaling mechanism of low-dose sorafenib treatment in NASH. We envision that this new therapeutic strategy for NASH has the potential to translate into a beneficial anti-NASH therapy with fewer adverse events than is observed in the drug's current use in HCC.

13.
Chemistry ; 26(37): 8254-8261, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32125735

RESUMO

Known for excellent stability, porosity and functionality, the high-valent Zr4+ metal-organic frameworks (Zr-MOFs) still meets synthetic challenge in modulating the strength of Zr-Ocarboxylate linkage. Herein we explore the unusual coordination dynamics of fluorinated Zr-MOFs by designing two trifluoromethyl modified ligands with distinct geometry preference to form a family of thermodynamic and kinetic products. The low-connecting kinetic Zr-MOFs possess substitutable coordination sites to endow Zr6 -cluster with extra dynamic behaviors, thus opening a post-synthetic pathway to sequential reassembly/disassembly processes. Comprehensive factors, including ligand geometry, Zr6 -cluster connectivity, acid modulator and reaction temperature/concentration, have been studied for controllable syntheses. The stability, hydrophobicity and gas adsorption/separation properties of obtained Zr-MOFs are explored. This work sheds light on the understanding of the dynamic coordination chemistry of Zr-MOFs beyond strong Zr-O bond, which poses a versatile platform for modification and functionalization of Zr-MOFs.

14.
Am J Physiol Regul Integr Comp Physiol ; 318(2): R351-R359, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31746626

RESUMO

Maternal high-fat diet (HFD) is associated with metabolic syndrome and cardiovascular diseases in adult offspring. Our previous study demonstrated that maternal HFD enhances pressor responses to ANG II or a proinflammatory cytokine (PIC), which is associated with increased expression of brain renin-angiotensin system (RAS) components and PICs in adult offspring. The present study further investigated whether inhibition of angiotensin-converting enzyme (ACE) or tumor necrosis factor-α (TNF-α) blocks sensitization of ANG II hypertension in offspring of HFD dams. All offspring were bred from dams with normal fat diet (NFD) or HFD starting two weeks before mating and maintained until weaning of the offspring. Then the weaned offspring were treated with an ACE inhibitor (captopril) or a TNF-α inhibitor (pentoxifylline) in the drinking water through the end of testing with a slow-pressor dose of ANG II. RT-PCR analyses of the lamina terminalis and paraventricular nucleus revealed upregulation of mRNA expression of several RAS components and PICs in male offspring of HFD dams when compared with age-matched offspring of NFD dams. The enhanced gene expression was attenuated by blockade of either RAS or PICs. Likewise, ANG II administration produced an augmented pressor response in offspring of HFD dams. This was abolished by either ACE or TNF-α inhibitor. Taken together, this study provides mechanistic evidence and a therapeutic strategy that systemic inhibition of the RAS and PICs can block maternal HFD-induced sensitization of ANG II hypertension, which is associated with attenuation of brain RAS and PIC expression in offspring.


Assuntos
Angiotensina II , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Captopril/farmacologia , Dieta Hiperlipídica , Hipertensão/prevenção & controle , Pentoxifilina/farmacologia , Efeitos Tardios da Exposição Pré-Natal , Inibidores do Fator de Necrose Tumoral/farmacologia , Fenômenos Fisiológicos da Nutrição Animal , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Modelos Animais de Doenças , Feminino , Hipertensão/induzido quimicamente , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Gravidez , Ratos Sprague-Dawley , Sistema Renina-Angiotensina/efeitos dos fármacos
15.
Angew Chem Int Ed Engl ; 58(47): 17033-17040, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31507037

RESUMO

We transformed the hydrophilic metal-organic framework (MOF) UiO-67 into hydrophobic UiO-67-Rs (R=alkyl) by introducing alkyl chains into organic linkers, which not only protected hydrophilic Zr6 O8 clusters to make the MOF interspace superoleophilic, but also led to a rough crystal surface beneficial for superhydrophobicity. The UiO-67-Rs displayed high acid, base, and water stability, and long alkyl chains offered better hydrophobicity. Good hydrophobicity/oleophilicity were also possible with mixed-ligand MOFs containing metal-binding ligands. Thus, a (super)hydrophobic MOF catalyst loaded with Pd centers efficiently catalyzed Sonogashira reactions in water at ambient temperature. Studies of the hydrophobic effects of the coordination interspace and the outer surface suggest a simple de novo strategy for the synthesis of superhydrophobic MOFs that combine surface roughness and low surface energy. Such MOFs have potential for environmentally friendly catalysis and water purification.

16.
Hepatology ; 70(5): 1750-1769, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31077413

RESUMO

Hepatic ischemia-reperfusion (IR) injury is the leading cause of liver dysfunction and failure after liver resection or transplantation and lacks effective therapeutic strategies. Here, we applied a systematic proteomic analysis to identify the prominent contributors to IR-induced liver damage and promising therapeutic targets for this condition. Based on an unbiased proteomic analysis, we found that toll-interacting protein (Tollip) expression was closely correlated with the hepatic IR process. RNA sequencing analysis and phenotypic examination showed a dramatically alleviated hepatic IR injury by Tollip deficiency both in vivo and in hepatocytes. Mechanistically, Tollip interacts with apoptosis signal-regulating kinase 1 (ASK1) and facilitates the recruitment of tumor necrosis factor receptor-associated factor 6 (TRAF6) to ASK1, leading to enhanced ASK1 N-terminal dimerization and the subsequent activation of downstream mitogen-activated protein kinase (MAPK) signaling. Furthermore, the Tollip methionine and phenylalanine motif and TRAF6 ubiquitinating activity are required for Tollip-regulated ASK1-MAPK axis activation. Conclusion: Tollip is a regulator of hepatic IR injury by facilitating ASK1 N-terminal dimerization and the resultant c-Jun N-terminal kinase/p38 signaling activation. Inhibiting Tollip or its interaction with ASK1 might be promising therapeutic strategies for hepatic IR injury.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Fígado/irrigação sanguínea , Proteômica , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/etiologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL
17.
BMC Genomics ; 20(1): 371, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31088355

RESUMO

BACKGROUND: Barbarea vulgaris is a wild cruciferous plant and include two distinct types: the G- and P-types named after their glabrous and pubescent leaves, respectively. The types differ significantly in resistance to a range of insects and diseases as well as glucosinolates and other chemical defenses. A high-density linkage map was needed for further progress to be made in the molecular research of this plant. RESULTS: We performed restriction site-associated DNA sequencing (RAD-Seq) on an F2 population generated from G- and P-type B. vulgaris. A total of 1545 SNP markers were mapped and ordered in eight linkage groups, which represents the highest density linkage map to date for the crucifer tribe Cardamineae. A total of 722 previously published genome contigs (50.2 Mb, 30% of the total length) can be anchored to this high density genetic map, an improvement compared to a previously published map (431 anchored contigs, 38.7 Mb, 23% of the assembly genome). Most of these (572 contigs, 31.2 Mb) were newly anchored to the map, representing a significant improvement. On the basis of the present high-density genetic map, 37 QTL were detected for eleven traits, each QTL explaining 2.9-71.3% of the phenotype variation. QTL of glucosinolates, leaf size and color traits were in most cases overlapping, possibly implying a functional connection. CONCLUSIONS: This high-density linkage map and the QTL obtained in this study will be useful for further understanding of the genetic of the B. vulgaris and molecular basis of these traits, many of which are shared in the related crop watercress.


Assuntos
Barbarea/genética , Mapeamento Cromossômico/métodos , Locos de Características Quantitativas , Análise de Sequência de DNA/métodos , Barbarea/fisiologia , DNA de Plantas/genética , Ligação Genética , Fenótipo , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Polimorfismo de Nucleotídeo Único
18.
World J Gastroenterol ; 25(13): 1580-1591, 2019 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-30983818

RESUMO

BACKGROUND: Early gastric cancer (EGC), compared with advanced gastric cancer (AGC), has a higher 5-year survival rate. However, due to the lack of typical symptoms and the difficulty in diagnosing EGC, no effective biomarkers exist for the detection of EGC, and gastroscopy is the only detection method. AIM: To provide new biomarkers with high specificity and sensitivity through analyzed the differentially expressed microRNAs (miRNAs) in EGC and AGC and compared them with those in benign gastritis (BG). METHODS: We examined the differentially expressed miRNAs in the plasma of 30 patients with EGC, AGC, and BG by miRNA chip analysis. Then, we analyzed and selected the significantly different miRNAs using bioinformatics. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) confirmed the relative transcription level of these miRNAs in another 122 patients, including patients with EGC, AGC, Helicobacter pylori (H. pylori)-negative gastritis (Control-1), and H. pylori-positive atrophic gastritis (Control-2). To establish a diagnostic model for the detection of plasma miRNA in EGC, we chose miRNAs that can be used to determine EGC and AGC from Control-1 and Control-2 and miRNAs in EGC from all other groups. RESULTS: Among the expression profiles of the miRNA chips in the three groups in the discovery set, of 117 aberrantly expressed miRNAs, 30 confirmed target prediction, whereas 14 were included as potential miRNAs. The RT-qPCR results showed that 14 potential miRNAs expression profiles in the two groups exhibited no differences in terms of H. pylori-negative gastritis (Control-1) and H. pylori-positive atrophic gastritis (Control-2). Hence, these two groups were incorporated into the Control group. A combination of four types of miRNAs, miR-7641, miR-425-5p, miR-1180-3p and miR-122-5p, were used to effectively distinguish the Cancer group (EGC + AGC) from the Control group [area under the curve (AUC) = 0.799, 95% confidence interval (CI): 0.691-0.908, P < 0.001]. Additionally, miR-425-5p, miR-24-3p, miR-1180-3p and miR-122-5p were utilized to distinguish EGC from the Control group (AUC = 0.829, 95%CI: 0.657-1.000, P = 0.001). Moreover, the miR-24-3p expression level in EGC was lower than that in the AGC (AUC = 0.782, 95%CI: 0.571-0.993, P = 0.029), and the miR-4632-5p expression level in EGC was significantly higher than that in AGC (AUC = 0.791, 95%CI: 0.574-1.000, P = 0.024). CONCLUSION: The differentially expressed circulatory plasma miR-425-5p, miR-1180-3p, miR-122-5p, miR-24-3p and miR-4632-5p can be regarded as a new potential biomarker panel for the diagnosis of EGC. The prediction and early diagnosis of EGC can be considerably facilitated by combining gastroscopy with the use of these miRNA biomarkers, thereby optimizing the strategy for effective detection of EGC. Nevertheless, larger-scale human experiments are still required to confirm our findings.


Assuntos
Biomarcadores Tumorais/sangue , Detecção Precoce de Câncer/métodos , MicroRNAs/sangue , Neoplasias Gástricas/diagnóstico , Adulto , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/isolamento & purificação , Biópsia , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Masculino , MicroRNAs/genética , MicroRNAs/isolamento & purificação , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Estômago/patologia , Neoplasias Gástricas/sangue , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
19.
Life Sci ; 216: 129-139, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30414426

RESUMO

AIMS: This study aims to investigate the pathophysiological role and mechanism of pigment epithelium-derived factor (PEDF) deletion in ovarian damage. METHODS: Female PEDF-knockout mice and their wild-type littermates were used in this study. Relevant tests were performed at 8-10 weeks or 32 weeks of age. KEY FINDINGS: Compared to the wild-type mice, the PEDF-knockout mice showed diminished ovarian reserve (DOR), worse ovum quality after injection to induce controlled ovarian stimulation, increased serum follicle stimulating hormone (FSH) level and an follicle stimulating hormone/luteinizing hormone (FSH/LH) ratio. Moreover, severe ovarian oxidative damage was found in ovaries of PEDF-knockout mice that mainly manifested as an accumulation of reactive oxygen species (ROS), NF­E2-related factor 2 (Nrf2) pathway activation, significantly upregulated expression of ROS-generating genes. Correspondingly, the PEDF-knockout mice exhibited lipid metabolism disorder and insulin resistance, which mainly manifested as obesity, abdominal fat accumulation, adipocyte enlargement, severe ectopic fat deposition, dyslipidemia, changes in adipokine levels, hyperglycemia, hyperinsulinemia, impaired glucose tolerance, impaired insulin tolerance and significantly declined protein kinase B (Akt) phosphorylation levels. SIGNIFICANCE: Loss of PEDF leads to ovarian oxidative damage accompanied by DOR in mice, this is related to PEDF deficiency induced severe insulin resistance and lipid metabolism disorder. Therefore, PEDF may be a potential target for the treatment of diseases related to ovarian oxidative damage.


Assuntos
Proteínas do Olho/genética , Fatores de Crescimento Neural/genética , Reserva Ovariana/fisiologia , Ovário/fisiopatologia , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Serpinas/genética , Gordura Abdominal/metabolismo , Animais , Proteínas do Olho/metabolismo , Feminino , Resistência à Insulina/genética , Resistência à Insulina/fisiologia , Metabolismo dos Lipídeos/genética , Metabolismo dos Lipídeos/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fatores de Crescimento Neural/metabolismo , Obesidade/patologia , Reserva Ovariana/genética , Estresse Oxidativo/genética , Serpinas/metabolismo , Regulação para Cima
20.
Inorg Chem ; 58(1): 61-64, 2019 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-30588809

RESUMO

A trifluoromethyl functionalized linker and Cu-O chain composed MOF, LIFM-100, was used as "crystalline sponge" to determine eight hardly crystallized liquids' configurations based on its flexibility conformation, suitable pore size, electron-rich channel environment, and low symmetric space group. The H bond interactions between host-guest and guest-guest were well analyzed.

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