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1.
Inflammopharmacology ; 32(1): 335-354, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38097885

RESUMO

BACKGROUND: The clinical efficacy and safety of intravenous immunoglobulin (IVIg) treatment for COVID-19 remain controversial. This study aimed to map the current status and gaps of available evidence, and conduct a meta-analysis to further investigate the benefit of IVIg in COVID-19 patients. METHODS: Electronic databases were searched for systematic reviews/meta-analyses (SR/MAs), primary studies with control groups, reporting on the use of IVIg in patients with COVID-19. A random-effects meta-analysis with subgroup analyses regarding study design and patient disease severity was performed. Our outcomes of interest determined by the evidence mapping, were mortality, length of hospitalization (days), length of intensive care unit (ICU) stay (days), number of patients requiring mechanical ventilation, and adverse events. RESULTS: We included 34 studies (12 SR/MAs, 8 prospective and 14 retrospective studies). A total of 5571 hospitalized patients were involved in 22 primary studies. Random-effects meta-analyses of very low to moderate evidence showed that there was little or no difference between IVIg and standard care or placebo in reducing mortality (relative risk [RR] 0.91; 95% CI 0.78-1.06; risk difference [RD] 3.3% fewer), length of hospital (mean difference [MD] 0.37; 95% CI - 2.56, 3.31) and ICU (MD 0.36; 95% CI - 0.81, 1.53) stays, mechanical ventilation use (RR 0.92; 95% CI 0.68-1.24; RD 2.8% fewer), and adverse events (RR 0.98; 95% CI 0.84-1.14; RD 0.5% fewer) of patients with COVID-19. Sensitivity analysis using a fixed-effects model indicated that IVIg may reduce mortality (RR 0.76; 95% CI 0.60-0.97), and increase length of hospital stay (MD 0.68; 95% CI 0.09-1.28). CONCLUSION: Very low to moderate certainty of evidence indicated IVIg may not improve the clinical outcomes of hospitalized patients with COVID-19. Given the discrepancy between the random- and fixed-effects model results, further large-scale and well-designed RCTs are warranted.


Assuntos
COVID-19 , Imunoglobulinas Intravenosas , Humanos , Imunoglobulinas Intravenosas/efeitos adversos , Estudos Prospectivos , Estudos Retrospectivos , Revisões Sistemáticas como Assunto
2.
Plant Physiol ; 189(2): 1037-1049, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35238391

RESUMO

The regulatory mechanisms that link WRKY gene expression to fruit ripening are largely unknown. Using transgenic approaches, we showed that a WRKY gene from wild strawberry (Fragaria vesca), FvWRKY48, may be involved in fruit softening and ripening. We showed that FvWRKY48 is localized to the nucleus and that degradation of the pectin cell wall polymer homogalacturonan, which is present in the middle lamella and tricellular junction zones of the fruit, was greater in FvWRKY48-OE (overexpressing) fruits than in empty vector (EV)-transformed fruits and less substantial in FvWRKY48-RNAi (RNA interference) fruits. Transcriptomic analysis indicated that the expression of pectate lyase A (FvPLA) was significantly downregulated in the FvWRKY48-RNAi receptacle. We determined that FvWRKY48 bound to the FvPLA promoter via a W-box element through yeast one-hybrid, electrophoretic mobility shift, and chromatin immunoprecipitation quantitative polymerase chain reaction experiments, and ß-glucosidase activity assays suggested that this binding promotes pectate lyase activity. In addition, softening and pectin degradation were more intense in FvPLA-OE fruit than in EV fruit, and the middle lamella and tricellular junction zones were denser in FvPLA-RNAi fruit than in EV fruit. We speculated that FvWRKY48 maybe increase the expression of FvPLA, resulting in pectin degradation and fruit softening.


Assuntos
Fragaria , Parede Celular/genética , Parede Celular/metabolismo , Fragaria/genética , Fragaria/metabolismo , Frutas/genética , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas , Pectinas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Polissacarídeo-Liases
3.
Molecules ; 28(24)2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38138466

RESUMO

The polysaccharides extracted from Aspidopterys obcordata are thought to have anti-urolithiasis activity in Drosophila kidney stones. This study aimed to assess the effects of different extraction solvents on the yield, chemical composition, and bioactivity of polysaccharides from A. obcordata. A. obcordata polysaccharides were extracted by using four solutions: hot water, HCl solution, NaOH solution, and 0.1 M NaCl. The results revealed that the extraction solvents significantly influenced the extraction yields, molecular weight distribution, monosaccharide compositions, preliminary structural characteristics, and microstructures of polysaccharides. The NaOH solution's extraction yield was significantly higher than the other extraction methods. Vitro antioxidant activity assays revealed that the NaOH solution extracted exhibited superior scavenging abilities towards DPPH and ABTS radicals and higher FRAP values than other polysaccharides. The vitro assays conducted for calcium oxalate crystallization demonstrated that four polysaccharides exhibited inhibitory effects on the nucleation and aggregation of calcium oxalate crystals, impeded calcium oxalate monohydrate growth, and induced calcium oxalate dihydrate formation. The NaOH solution extracted exhibited the most pronounced inhibition of calcium oxalate crystal nucleation, while the hot water extracted demonstrated the most significant suppression of calcium oxalate crystal aggregation. Therefore, it can be inferred that polysaccharides extracted with NaOH solution exhibited significant potential as a viable approach for extracting polysaccharides from stems due to their superior yield and the remarkable bioactivity of the resulting products.


Assuntos
Oxalato de Cálcio , Polissacarídeos , Oxalato de Cálcio/química , Solventes , Hidróxido de Sódio , Polissacarídeos/farmacologia , Polissacarídeos/química , Água
4.
Acta Pharmacol Sin ; 43(5): 1167-1179, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34893685

RESUMO

The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing globally, being the most widespread form of chronic liver disease in the west. NAFLD includes a variety of disease states, the mildest being non-alcoholic fatty liver that gradually progresses to non-alcoholic steatohepatitis, fibrosis, cirrhosis, and eventually hepatocellular carcinoma. Small non-coding single-stranded microRNAs (miRNAs) regulate gene expression at the miRNA or translational level. Numerous miRNAs have been shown to promote NAFLD pathogenesis and progression through increasing lipid accumulation, oxidative stress, mitochondrial damage, and inflammation. The miR-23-27-24 clusters, composed of miR-23a-27a-24-2 and miR-23b-27b-24-1, have been implicated in various biological processes as well as many diseases. Herein, we review the current knowledge on miR-27, miR-24, and miR-23 in NAFLD pathogenesis and discuss their potential significance in NAFLD diagnosis and therapy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Hepatopatia Gordurosa não Alcoólica , Carcinoma Hepatocelular/patologia , Humanos , Fígado/metabolismo , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo
5.
Acta Pharmacol Sin ; 43(9): 2373-2385, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35046516

RESUMO

The protein arginine methyltransferase 5 (PRMT5), which is highly expressed in tumour tissues, plays a crucial role in cancer development. However, the mechanism by which PRMT5 promotes cancer growth is poorly understood. Here, we report that PRMT5 contributes to lipid metabolism reprogramming, tumour growth and metastasis depending on the SIRT7-mediated desuccinylation of PRMT5 K387 in tumours. Mass spectrometric analysis identified PRMT5 lysine 387 as its succinylation site. Moreover, the desuccinylation of PRMT5 K387 enhances the methyltransferase activity of PRMT5. SIRT7 catalyses the desuccinylation of PRMT5 in cells. The SIRT7-mediated dessuccinylation of PRMT5 lysine 387 fails to bind to STUB1, decreasing PRMT5 ubiquitination and increasing the interaction between PRMT5 and Mep50, which promotes the formation of the PRMT5-Mep50 octamer. The PRMT5-Mep50 octamer increases PRMT5 methyltransferase activity, leading to arginine methylation of SREBP1a. The symmetric dimethylation of SREBP1a increases the levels of cholesterol, fatty acid, and triglyceride biogenesis in the cells, escaping degradation through the ubiquitin-proteasome pathway. Functionally, the desuccinylation of PRMT5 K387 promotes lipid metabolism reprogramming, tumour growth and metastasis in vitro and in vivo in tumours.


Assuntos
Neoplasias , Sirtuínas , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Humanos , Metabolismo dos Lipídeos , Lisina , Proteína-Arginina N-Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/metabolismo , Sirtuínas/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
6.
Sensors (Basel) ; 22(20)2022 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-36298108

RESUMO

The printed circuit board (PCB) is the core control unit of electromechanical equipment. In order to determine the influence of the coupling vibration caused by vehicle-road interaction on the PCB reliability of roadside electromechanical equipment, first, the dynamic load of the vehicle tire is solved by establishing the dynamic model of a vehicle road. Then, the acceleration response data generated by road vibration are obtained by solving the road finite element model. Finally, the power density spectrum of the acceleration response is taken as input excitation, and the deformation response of the PCB under vehicle-road coupling vibration is analyzed. The experimental results show that when the vehicle is driving close to the roadside, the vibration caused by vehicle-road coupling will lead to a large deformation of the PCB, and the deformation value reaches 0.170 mm, which can cause structural damage to the PCB. This shows that the vehicle-road coupling vibration can affect the reliability of the roadside electromechanical equipment; thus, the optimal design of the PCB layout is created. After optimization, the first-order modal frequency of the PCB is increase by 5.4%, which reduces the risk of the components breaking away from the PCB substrate.


Assuntos
Condução de Veículo , Reprodutibilidade dos Testes , Aceleração , Vibração
7.
Int J Mol Sci ; 23(12)2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35743224

RESUMO

Dendrobium sinense, an endemic medicinal herb in Hainan Island, is rich in bibenzyls. However, the key rate-limited enzyme involved in bibenzyl biosynthesis has yet to be identified in D. sinense. In this study, to explore whether there is a significant difference between the D. sinense tissues, the total contents of bibenzyls were determined in roots, pseudobulbs, and leaves. The results indicated that roots had higher bibenzyl content than pseudobulbs and leaves. Subsequently, transcriptomic sequencings were conducted to excavate the genes encoding type III polyketide synthase (PKS). A total of six D. sinense PKS (DsPKS) genes were identified according to gene function annotation. Phylogenetic analysis classified the type III DsPKS genes into three groups. Importantly, the c93636.graph_c0 was clustered into bibenzyl synthase (BBS) group, named as D. sinense BBS (DsBBS). The expression analysis by FPKM and RT-qPCR indicated that DsBBS showed the highest expression levels in roots, displaying a positive correlation with bibenzyl contents in different tissues. Thus, the recombinant DsBBS-HisTag protein was constructed and expressed to study its catalytic activity. The molecular weight of the recombinant protein was verified to be approximately 45 kDa. Enzyme activity analysis indicated that the recombinant DsBBS-HisTag protein could use 4-coumaryol-CoA and malonyl-CoA as substrates for resveratrol production in vitro. The Vmax of the recombinant protein for the resveratrol production was 0.88 ± 0.07 pmol s-1 mg-1. These results improve our understanding with respect to the process of bibenzyl biosynthesis in D. sinense.


Assuntos
Bibenzilas , Dendrobium , Bibenzilas/química , Coenzima A , Dendrobium/química , Dendrobium/genética , Óxido Nítrico Sintase , Filogenia , Proteínas Recombinantes , Resveratrol
8.
J Sci Food Agric ; 102(10): 4373-4383, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35066866

RESUMO

BACKGROUND: Probiotics exhibit antibiotic properties and are capable of treating certain bacterial infections, including diarrhea. Therefore, the aim of this study is to investigate the effects of dietary supplementation with multispecies probiotic (MSP) on diarrhea, average daily gain (ADG) and intestinal development of neonatal calves challenged with Escherichia coli K99. RESULTS: Thirty-six neonatal Holstein calves were randomly assigned to three treatment groups. After E. coli K99 challenge, calves in the control (C) and MSP treatment groups had significantly higher ADG and feed efficiency, and significantly lower fecal scores than those of calves in the diarrhea (D) group. The mean time of diarrhea resolution was 4.5 and 3.1 days for calves in the D and MSP treatment groups, respectively. Furthermore, the structures of the various segments (duodenum, jejunum and ileum) of the small intestine of the calves, activities of several small intestinal enzymes, and expression of several energy metabolism-related genes in the small intestine segments were significantly affected by MSP treatments. CONCLUSION: Dietary supplementation of MSP had a positive effect in treating calf diarrhea; it improved ADG and feed efficiency and promoted development of the small intestine. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Assuntos
Escherichia coli , Probióticos , Ração Animal/análise , Animais , Bovinos , Diarreia/microbiologia , Diarreia/veterinária , Dieta/veterinária , Crescimento e Desenvolvimento , Probióticos/farmacologia , Desmame
9.
Med Sci Monit ; 27: e930921, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34408123

RESUMO

BACKGROUND Diabetes is related to higher risk of multiple cancers. This study aimed to explore the effect and mechanism of diabetes on liver metastasis of CRC. MATERIAL AND METHODS Overall and liver metastasis-free survival in diabetic and non-diabetic CRC patients were compared by Kaplan-Meier analysis. Expression of alphavß6 was detected by immunohistochemistry in clinical specimens. Effects of hyperglycemia on alphavß6 expression in colon cancer cells were assessed by western blot, real-time PCR, and flowcytometry. Effects of hyperglycemia on migration and invasion were demonstrated by Transwell assay. Expression and activity of MMP-9 and MMP-2 were determined by real-time PCR and gelatin zymography. Liver metastatic nodules were counted and b6 expression was detected by western blot in a liver metastasis mouse model. RESULTS CRC patients with diabetes had poorer overall and liver metastasis-free survival, and diabetes was associated with higher alphavß6 expression in CRC specimens. Hyperglycemia promoted the invasion and migration of colon cancer cells, and upregulated the expression and activity of MMP-9, which were attenuated by inhibition of alphavß6. Hyperglycemia upregulated the expression of ß6 and cell surface expression of avb6, which was reduced by ERK inhibitor. The in vitro results were confirmed in vivo in the mouse model. CONCLUSIONS Our study demonstrated the enhancing effect of hyperglycemia on liver metastasis of CRC, and showed that alphavß6 was involved in this process, suggesting that control of glucose levels and inhibition of alphavß6 can reduce the risk of liver metastasis in diabetic CRC patients.


Assuntos
Antígenos de Neoplasias/metabolismo , Neoplasias Colorretais/sangue , Hiperglicemia/metabolismo , Integrinas/metabolismo , Adulto , Animais , Antígenos de Neoplasias/genética , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal , Feminino , Expressão Gênica , Humanos , Hiperglicemia/patologia , Integrinas/genética , Neoplasias Hepáticas/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Metástase Neoplásica , RNA Longo não Codificante , Regulação para Cima
10.
Int Braz J Urol ; 47(1): 93-99, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32271508

RESUMO

HYPOTHESIS: Endoclip can be used as fiducial marker in urology. OBJECTIVE: To assess the feasibility, cost effectiveness and reliability of endoclips as novel fiducial markers in precision radiotherapy, as part of a trimodality bladder-preserving treatment (TBPT) of muscle-invasive bladder carcinoma. MATERIALS AND METHODS: This retrospective study was performed at Weifang People's Hospital (Weifang, China) from January 2015 to June 2018. A total of 15 patients underwent TBPT. Endoclips were applied to healthy edges of the resected bladder wall as novel fiducial markers. Radio-sensitizing chemotherapy and routine precision radiotherapy were given. The number and position of the endoclips during radiotherapy sessions were monitored. Complications and tumor recurrence were analyzed. RESULTS: The mean age (±standard deviation) of the patients was 67±10 years (range 46-79). There were 3 females and 12 males. Forty-nine endoclips were applied in all patients (3.3±0.8). The tumor was completely visibly resected in all patients. The number of endoclips remained the same through the planned last radiotherapy session (3.3±0.8), i.e., none were lost. All endoclips were removed after the last radiotherapy session. The average number of follow-up months was 38.9±13.2 (range 11-52). There were no procedure-related complications at discharge or follow-up. At one-year, overall recurrence-free survival was 93.3%. Two patients had recurrences at 18 months and 10 months after TBPT, respectively, and salvage radical cystectomy was performed with no further recurrences. Another patient died due to metastasis 9 months after the completion of therapy. CONCLUSIONS: Endoclips are reliable, safe and cost-effective as novel fiducial markers in precision-radiotherapy post-TBPT.


Assuntos
Carcinoma , Neoplasias da Bexiga Urinária , Idoso , China , Terapia Combinada , Cistectomia , Estudos de Viabilidade , Feminino , Marcadores Fiduciais , Humanos , Masculino , Pessoa de Meia-Idade , Músculos , Invasividade Neoplásica , Recidiva Local de Neoplasia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Resultado do Tratamento , Bexiga Urinária , Neoplasias da Bexiga Urinária/radioterapia , Neoplasias da Bexiga Urinária/cirurgia
11.
J Org Chem ; 85(6): 4067-4078, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32049523

RESUMO

A new traceless directing group, 2-(hydroxymethyl)pyridine, has been reported for the Cp*-free cobalt-catalyzed C-H activation/annulation reaction to synthesize isoquinolinones. The reaction exhibits good functional group tolerance, affording products in good to excellent isolated yields under mild conditions. Notably, the directing group can be removed directly in situ along the catalytic process.

12.
J Org Chem ; 85(17): 11190-11199, 2020 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-32786615

RESUMO

An efficient Cp*Co(III)-catalyzed C-H bond amidation of indolines at the C7-position using dioxazolone as amidating reagents was first reported. N-Methyl-N-(pyrimidin-2-yl)aniline was also found to be a competent coupling partner. This protocol exhibits several unique characteristics, including excellent isolated yields, good functional group tolerance, and operational convenience. Derivatization reactions revealed this method has great potential for applications in synthesis.

13.
Adv Skin Wound Care ; 33(9): 1-10, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32740027

RESUMO

OBJECTIVE: To gain insight into the magnitude of the problem of chronic skin wounds in a hospital in northern China. METHODS: Researchers conducted a retrospective analysis of electronic health records of cases and controls, including 1,977 patients with chronic skin wounds admitted to the hospital's medical wards over 5 years. Multiple logistic regression was used to establish factors correlating with the development of chronic wounds. RESULTS: The total prevalence of chronic wounds increased over the study period, and the occurrence of these wounds was significantly correlated with male sex, married status, unemployment, autumn season, and older age. The primary causes of chronic wounds were infection and diabetic ulcer. There were proportionally more wounds secondary to disease than traumatic wounds. The mean duration of hospitalization for patients with wounds was 13 days, and patients were readmitted an average of 10 times. CONCLUSIONS: With the rapidly aging population in China, disability and chronic wounds are significant problems. Reducing hospital lengths of stay and readmissions remains a challenge. Palliative care may be appropriate for the management of some chronic wounds to prevent and treat further complications. Establishing funding guarantees and the reasonable allocation of health resources is required.


Assuntos
Pacientes Internados/estatística & dados numéricos , Ferimentos e Lesões/epidemiologia , Ferimentos e Lesões/terapia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , China , Pé Diabético/epidemiologia , Pé Diabético/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Distribuição por Sexo
14.
Rev Esp Enferm Dig ; 112(6): 462-466, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32450701

RESUMO

OBJECTIVE: the aim of this study was to investigate the expression of integrin αvß6 in normal, hepatitis B, HBV-associated cirrhosis and HBV-associated HCC liver tissues. METHODS: immunohistochemistry and real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) were used to study the expression of integrin αvß6 in HBV-associated cirrhosis (n = 88), chronic hepatitis B ( n= 11), HBV-associated HCC (n = 84) and normal (n = 10) human liver tissues. RESULTS: the expression of integrin αvß6 was significantly upregulated in HBV-associated liver cirrhosis and the expression increased with an increase in severity of cirrhosis. Furthermore, it was moderately or weakly expressed in chronic hepatitis B and HBV-associated HCC liver tissues when compared to normal liver tissue. CONCLUSION: integrin αvß6 could be a predictive marker for the progression of liver cirrhosis associated with HBV infection. Further studies are needed to determine the association between the expression of integrin αvß6 in hepatitis B and HBV-associated HCC liver tissues.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Antígenos de Neoplasias/metabolismo , Vírus da Hepatite B , Hepatite B Crônica/complicações , Humanos , Integrinas/metabolismo , Cirrose Hepática/complicações
15.
Cancer Cell Int ; 19: 155, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31171919

RESUMO

BACKGROUND: Abnormal expression of the eukaryotic initiation factor 3 (eIF3) subunits plays critical roles in tumorigenesis and progression, and also has potential prognostic value in cancers. However, the expression and clinical implications of eIF3 subunits in glioma remain unknown. METHODS: Expression data of eIF3 for patients with gliomas were obtained from the Chinese Glioma Genome Atlas (CGGA) (n = 272) and The Cancer Genome Atlas (TCGA) (n = 595). Cox regression, the receiver operating characteristic (ROC) curves and Kaplan-Meier analysis were used to study the prognostic value. Gene oncology (GO) and gene set enrichment analysis (GSEA) were utilized for functional prediction. RESULTS: In both the CGGA and TCGA datasets, the expression levels of eIF3d, eIF3e, eIF3f, eIF3h and eIF3l highly were associated with the IDH mutant status of gliomas. The expression of eIF3b, eIF3i, eIF3k and eIF3m was increased with the tumor grade, and was associated with poorer overall survival [All Hazard ratio (HR) > 1 and P < 0.05]. By contrast, the expression of eIF3a and eIF3l was decreased in higher grade gliomas and was associated with better overall survival (Both HR < 1 and P < 0.05). Importantly, the expression of eIF3i (located on chromosome 1p) and eIF3k (Located on chromosome 19q) were the two highest risk factors in both the CGGA [eIF3i HR = 2.068 (1.425-3.000); eIF3k HR = 1.737 (1.166-2.588)] and TCGA [eIF3i HR = 1.841 (1.642-2.064); eIF3k HR = 1.521 (1.340-1.726)] databases. Among eIF3i, eIF3k alone or in combination, the expression of eIF3i was the more robust in stratifying the survival of glioma in various pathological subgroups. The expression of eIF3i was an independent prognostic factor in IDH-mutant lower grade glioma (LGG) and could also predict the 1p/19q codeletion status of IDH-mutant LGG. Finally, GO and GSEA analysis showed that the elevated expression of eIF3i was significantly correlated with the biological processes of cell proliferation, mRNA processing, translation, T cell receptor signaling, NF-κB signaling and others. CONCLUSIONS: Our study reveals the expression alterations during glioma progression, and highlights the prognostic value of eIF3i in IDH-mutant LGG.

16.
Org Biomol Chem ; 17(48): 10167-10171, 2019 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-31782473

RESUMO

A strategy for the synthesis of isoxazolidine/1,2-oxazinane-fused isoquinolin-1(2H)-ones from alkyne-tethered N-alkoxyamides is described, in which cheap Mn(acac)2 is used as a catalyst to facilitate a radical cascade annulation. The method features mild conditions, additive-free reaction and broad substrate scope. It is the first example via manganese/air catalytic systems to construct isoquinolin-1(2H)-one heterocycles.

17.
J Gastroenterol Hepatol ; 34(1): 12-21, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30311701

RESUMO

BACKGROUND AND AIM: Although treatment with direct-acting antivirals has dramatically improved morbidity and mortality attributable to chronic hepatitis C virus infection, universal access to these medicines has been slow in the Asia-Pacific region and Russia. This study evaluated efficacy and safety of elbasvir/grazoprevir in participants with hepatitis C virus infection from Asia-Pacific countries and Russia (C-CORAL). METHODS: C-CORAL was a phase 3, randomized, placebo-controlled study (NCT02251990). Treatment-naive, HIV-negative, cirrhotic and non-cirrhotic participants with chronic hepatitis C genotype 1, 4, or 6 infection were randomized to elbasvir 50 mg/grazoprevir 100 mg once daily for 12 weeks (immediate-treatment group) or placebo followed by deferred treatment with elbasvir/grazoprevir (deferred-treatment group). The primary efficacy outcome was sustained virologic response at 12 weeks, and the primary safety outcome was a comparison between the immediate-treatment group and placebo phase of the deferred-treatment group. RESULTS: A total of 489 participants were randomized (immediate-treatment group, n = 366; deferred-treatment group, n = 123). Sustained virologic response at 12 weeks in the combined immediate/deferred-treatment groups was 94.4% (459/486; 95% confidence interval = 92.4-96.5%). Sustained virologic response at 12 weeks was 98.2% in participants with genotype 1b, 91.9% with genotype 1a, and 66.7% with genotype 6 infection. Similar rates of adverse events and drug-related adverse events were seen in the immediate-treatment group versus placebo phase of the deferred-treatment group (51.0% vs 50.4% and 21.4% vs 21.1%). CONCLUSIONS: Elbasvir/grazoprevir for 12 weeks represents an effective and well-tolerated treatment option for treatment-naive people with genotype 1 infection from Asia-Pacific countries and Russia.


Assuntos
Antivirais/uso terapêutico , Benzofuranos/uso terapêutico , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Imidazóis/uso terapêutico , Quinoxalinas/uso terapêutico , Adulto , Alanina Transaminase/sangue , Antivirais/efeitos adversos , Aspartato Aminotransferases/sangue , Austrália , Benzofuranos/efeitos adversos , Método Duplo-Cego , Combinação de Medicamentos , Farmacorresistência Viral/genética , Ásia Oriental , Feminino , Genótipo , Hepacivirus/enzimologia , Humanos , Imidazóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Quinoxalinas/efeitos adversos , Federação Russa , Resposta Viral Sustentada , Tailândia , Vietnã , Proteínas não Estruturais Virais/metabolismo , Adulto Jovem
18.
Echocardiography ; 36(9): 1639-1645, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31393630

RESUMO

OBJECTIVES: The purpose of this study was to assess the factors influencing the late diastolic vortex in normal and abnormal ventricles. METHODS: Color Doppler data in left ventricle (LV) were acquired from apical long-axis view and analyzed using vector flow mapping in 57 patients with coronary artery disease, 57 patients with dilated cardiomyopathy, and 53 healthy volunteers. RESULTS: In normals, corrected area and flux of the end-diastolic vortex were positively correlated with transmitral A velocity and heart rate. Subjects with E/A <1 had higher vortex flux than those with E/A >1. Heart rate was the only independent predictor of corrected vortex area (R2  = .170, P = .004), and transmitral A velocity and heart rate were the independent predictors of corrected vortex flux (R2  = .490, P < .001). Patients with various mitral filling patterns showed significant differences in vortex area and flux. The vortex area and flux were positively correlated with transmitral i velocity and a'. Transmitral A velocity was the only independent predictor of corrected vortex area (R2  = .180, P < .001), while transmitral A velocity, heart rate, LV end-systolic short diameter, and end-diastolic long diameter were the independent determinants of corrected vortex flux (R2  = .593, P < .001). CONCLUSIONS: The end-diastolic vortex is formed and mainly affected by the late LV filling. The compensatory atrial contraction may enhance the end-diastolic vortex that facilitates coupling between diastole and systole. LV size can influence the end-diastolic vortex in patients with LV dysfunction and enlargement.


Assuntos
Cardiomiopatia Dilatada/diagnóstico por imagem , Doença da Artéria Coronariana/diagnóstico por imagem , Ecocardiografia Doppler em Cores , Adolescente , Adulto , Idoso , Velocidade do Fluxo Sanguíneo/fisiologia , Cardiomiopatia Dilatada/fisiopatologia , Estudos de Casos e Controles , Doença da Artéria Coronariana/fisiopatologia , Diástole/fisiologia , Eletrocardiografia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Volume Sistólico/fisiologia
19.
Entropy (Basel) ; 21(6)2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-33267262

RESUMO

Hydrological regionalization is a useful step in hydrological modeling and prediction. The regionalization is not always straightforward, however, due to the lack of long-term hydrological data and the complex multi-scale variability features embedded in the data. This study examines the multiscale soil moisture variability for the simulated data on a grid cell base obtained from a large-scale hydrological model, and clusters the grid-cell based soil moisture data using wavelet-based multiscale entropy and principal component analysis, over the Xijiang River basin in South China, for the period of 2002-2010. The effective regionalization, for 169 grid cells with the special resolution of 0.5° × 0.5°, produced homogeneous groups based on the pattern of wavelet-based entropy information. Four distinct modes explain 80.14% of the total embedded variability of the transformed wavelet power across different timescales. Moreover, the possible implications of the regionalization results for local hydrological applications, such as parameter estimation for an ungagged catchment and designing a uniform prediction strategy for a sub-area in a large-scale basin, are discussed.

20.
Biochem Cell Biol ; 96(6): 752-760, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29874469

RESUMO

MicroRNAs are critical regulators of the development and progression of laryngeal squamous cell carcinoma (LSCC). However, the role of microRNA-154 (miR-154) in the development and progression of LSCC has not been clarified. We found that down-regulated miR-154 expression in LSCC tissues was associated with poorer prognosis in LSCC patients. MiR-154 over-expression inhibited the proliferation, clonogenicity, and migration of LSCC cells and induced cell cycle arrest, which were reversed by miR-154 inhibition. MiR-154 targeted GALNT7 expression by reducing GALNT7-regulated luciferase activity in LSCC cells while up-regulating GALNT7 mRNA transcription in LSCC tissues and cells. GALNT7 silencing significantly attenuated the proliferation, clonogenicity, and migration of LSCC cells and induced cell cycle arrest. Finally, intravenous treatment with lentivirus for miR-154, but not scrambled control miRNA, significantly restrained the growth of implanted LSCC Hep-2 tumors and decreased the tumor mass by reducing GALNT7 expression in mice. Therefore, miR-154 may serve as a novel prognostic marker and therapeutic target for LSCC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/patologia , MicroRNAs/genética , N-Acetilgalactosaminiltransferases/deficiência , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Pontos de Checagem do Ciclo Celular , Movimento Celular , Proliferação de Células , Células Cultivadas , Feminino , Humanos , Neoplasias Laríngeas/metabolismo , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , N-Acetilgalactosaminiltransferases/genética , N-Acetilgalactosaminiltransferases/metabolismo , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Polipeptídeo N-Acetilgalactosaminiltransferase
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