Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 43
Filtrar
1.
Mol Med ; 28(1): 46, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35505281

RESUMO

BACKGROUND: Risperidone, an atypical antipsychotic, impedes serotonin and dopamine receptor systems. Meanwhile, tumor necrosis factor-α (TNF-α) is known to participate in regulating osteoblast functions. Consequently, the current study aimed to investigate whether the influences of Risperidone on osteoblast functions are associated with TNF-α and special AT-rich sequence-binding protein (SATB2). METHODS: Firstly, we searched the DGIdb, MEM and GeneCards databases to identify the critical factors involved in the effects of Risperidone on osteoblasts, as well as their interactions. Afterwards, osteoblast cell line MC3T3-E1 was transduced with lentivirus carrying si-TNF-α, si-SATB2 or both and subsequently treated with Risperidone. Various abilities including differentiation, autophagy and apoptosis of osteoblasts were examined after different treatments. Finally, animal experiments were performed with Risperidone alone or together with lentivirus to verify the function of Risperidone in vivo and the mechanism. RESULTS: It was found that Risperidone might promote TNF-α expression, thereby inhibiting the expression of SATB2 to affect the autophagy and apoptosis in osteoblasts. Furthermore, as shown by our experimental findings, Risperidone treatment inhibited the differentiation and autophagy, and promoted the apoptosis of osteoblasts, as evidenced by elevated levels of OPG, p62, cleaved PARP1, cleaved caspase-3, cleaved caspase-8, and cleaved caspase-9, and reduced levels of LC3 II/I, Beclin1, collagen I, and RANKL. In addition, Risperidone was also found to elevate the expression of TNF-α to down-regulate SATB2, thereby inhibiting the differentiation and autophagy and enhancing the apoptosis of osteoblasts in vitro and in vivo. CONCLUSIONS: Collectively, our findings indicated that Risperidone affects the differentiation of osteoblasts by inhibiting autophagy and enhancing apoptosis via TNF-α-mediated down-regulation of SATB2.


Assuntos
Antipsicóticos , Risperidona , Animais , Antipsicóticos/metabolismo , Antipsicóticos/farmacologia , Apoptose , Autofagia , Osteoblastos , Risperidona/metabolismo , Risperidona/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
2.
Cell Death Discov ; 8(1): 244, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35508474

RESUMO

Pyroptosis is inflammation-associated caspase-1-dependent programmed cell death, which confers a crucial role in sepsis. The present study intends to investigate the regulatory network and function of the microarray-predicted YTHDF1 in caspase-1-dependent pyroptosis of sepsis. Peripheral blood of patients with sepsis was collected to determine WWP1 and YTHDF1 expression. An in vitro sepsis cell model was induced in RAW264.7 cells using lipopolysaccharide (LPS) and ATP and an in vivo septic mouse model by cecal ligation and perforation (CLP). After gain- and loss-of-function assays in vitro and in vivo, TNF-α and IL-1ß levels and the cleavage of gasdermin-D (GSDMD) were detected by ELISA and Western blot assay, followed by determination of lactate dehydrogenase (LDH) activity. Immunoprecipitation and meRIP assay were performed to detect the ubiquitination of NLRP3 and the m6A modification of WWP1 mRNA. The binding of WWP1 to YTHDF1 was explored using RIP-RT-qPCR and dual luciferase gene reporter assay. It was noted that WWP1 and YTHDF1 were downregulated in clinical sepsis samples, LPS + ATP-treated RAW264.7 cells, and CLP-induced mice. The ubiquitination of NLRP3 was promoted after overexpression of WWP1. WWP1 translation could be promoted by YTHDF1. Then, WWP1 or YTHDF1 overexpression diminished LDH activity, NLRP3 inflammasomes and caspase-1-mediated cleavage of GSDMD in LPS + ATP-induced RAW264.7 cells. Overexpressed YTHDF1 restrained inflammatory response in CLP-induced mice. Collectively, the alleviatory effect of m6A reader protein YTHDF1 may be achieved through promotion of NLRP3 ubiquitination and inhibition of caspase-1-dependent pyroptosis by upregulating WWP1.

3.
Chemistry ; : e202201018, 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35420241

RESUMO

Enantioselective, intermolecular alkene arylamination was achieved through gold redox catalysis. Screening of ligands revealed chiral P,N ligands as the optimal choice, giving alkene aminoarylation with good yields (up to 80 %) and excellent stereoselectivity (up to 99 : 1 er). As the first example of enantioselective gold redox catalysis, this work confirmed the feasibility of applying a chiral ligand at the gold(I) stage, with the stereodetermining step (SDS) at the gold(III) intermediate, thus opening up a new way to conduct gold redox catalysis with stereochemistry control.

4.
Front Oncol ; 12: 800291, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35296014

RESUMO

Background: Perturbation of tryptophan (TRP) metabolism contributes to the immune escape of cancer; however, the explored TRP metabolites are limited, and their efficacy in clarifying the susceptibility and progression of esophageal cancer (EC) remains ambiguous. Our study sought to evaluate the effects of the TRP metabolic profile on the clinical outcomes of EC using a Chinese population cohort; and to develop a risk prediction model targeting TRP metabolism. Method: A total of 456 healthy individuals as control subjects and 393 patients with EC who were followed up for one year as case subjects were enrolled. Quantification of the plasma concentrations of TRP and its metabolites was performed using HPLC-MS/MS. The logistic regression model was applied to evaluate the effects of the clinical characteristics and plasma metabolites of the subjects on susceptibility and tumor metastasis events, whereas Cox regression analysis was performed to assess the overall survival (OS) of the patients. Results: Levels of creatinine and liver enzymes were substantially correlated with multiple metabolites/metabolite ratios in TRP metabolism, suggesting that hepatic and renal function would exert effects on TRP metabolism. Age- and sex-matched case-control subjects were selected using propensity score matching. Plasma exposure to 5-HT was found to be elevated 3.94-fold in case subjects (N = 166) compared to control subjects (N = 203), achieving an AUC of 0.811 for predicting susceptibility event. Subsequent correlation analysis indicated that a higher plasma exposure to 5-HIAA significantly increased the risk of lymph node metastasis (OR: 2.16, p = 0.0114). Furthermore, it was figured out that OS was significantly shorter for patients with elevated XA/KYN ratio (HR: 1.99, p = 0.0016), in which medium and high levels of XA/KYN versus low level had a significantly lower OS (HR: 0.48, p = 0.0080 and HR: 0.42, p = 0.0031, respectively). Conclusion: This study provides a pivotal basis for targeting endogenous TRP metabolism as a potential therapeutic intervention.

5.
Front Pharmacol ; 12: 739749, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34744722

RESUMO

Objective: The aim of the present study is to explore the combination of dexmedetomidine (DXM) and tramadol (TMD) on sedative effect in patients with pregnancy-induced hypertension (PIH). Methods: A total of 356 patients with pregnancy-induced hypertension (PIH) were randomly divided into three groups: DXM, TMD and DXM + TMD groups. These patients were treated with different doses of DXM, TMD or combination of DXM and TMD by a patient-controlled intravenous injection device. The scores of static pain and dynamic pain, sedation degree, and adverse reaction were recorded. The plasma levels of inflammatory mediators IL-10 and C-reactive protein (CRP), and the serum level of p-p38-MAPK were evaluated. Results: It was found that administration with DXM 1.0 µg/kg/h + TMD 700 mg and DXM 2.0 µg/kg/h + TMD 600 mg result in stronger sedative effect than single administration with DXM or TMD. The mean arterial pressure (MAP) and heart rate (HR) of patients with PIH were decreased with the combinational treatment of DXM and TMD. Interestingly, the PIH patients injected with DXM 1.0 µg/kg/h + TMD 700 mg and DXM 2.0 µg/kg/h + TMD 600 mg showed stronger sedative effect. In addition, the plasma level of level of IL-10 was increased and CRP decreased. The serum level of p-p38/MAPK was decreased. Conclusion: Taken together, our study indicates that combination of DXM and TMD effectively lowers blood pressure and reduces inflammation through increasing the level of IL-10, reducing CRP and inhibiting p-p38/MAPK in patients with PIH. This study suggests that the combination of DXM and TMD could be an anesthetic choice in the management of PIH.

6.
Iran J Public Health ; 50(3): 566-572, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34178804

RESUMO

BACKGROUND: To explore the effects of risk factors-based nursing management on the occurrence of pressure sores in hospitalized patients. METHODS: From Jan 2018 to Jun 2018, 289 hospitalized patients were divided into pressure sores group [100] and control group [189] for retrospective analysis. Overall, 260 hospitalized patients from Jun 2018 to Dec 2018 were followed up for nursing intervention. Overall 130 patients received risk factors-based nursing case management were in the intervention group, whereas 130 patients who received routine nursing care were in the control group. The chi-square test and t-test were used to compare the count data and the measurement data between groups, respectively. RESULTS: Age, body weight and proportions of patients with impaired nutritional intake, diabetes or stroke in pressure sores group were higher than those in normal group (P<0.05). Hospital stay and operative time in pressure sores group was longer than those in normal group (P<0.05). The frequency of assistant activity in pressure sores group was significantly lower than that in control group (P<0.05).In addition, the score of uroclepsia in pressure sores group was lower than that in normal group (P<0.05). Patients in the intervention group showed lower risk for pressure sores and more satisfied than patients in control group (P<0.001). CONCLUSION: Advanced age, high body weight, diabetes and stroke, long hospital stay, long operative time, poor nutritional status and severe uroclepsia were independent risk factors of pressure sores. Risk factors-based nursing case management can effectively reduce the occurrence and risk of pressure sores for hospitalized patients.

7.
Invest Ophthalmol Vis Sci ; 62(3): 30, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33749721

RESUMO

Purpose: This study aims to reveal retinal abnormities in a spontaneous diabetic nonhuman primate model and explore the mechanism of featured injuries. Methods: Twenty-eight cynomolgus monkeys were identified to suffer from spontaneous type 2 diabetes from a colony of more than eight-hundred aged monkeys, and twenty-six age-matched ones were chosen as controls. Their blood biochemistry profiles were determined and retinal changes were examined by multimodal imaging, hematoxylin and eosin staining, and immunofluorescence. Retinal pigment epithelium (RPE) cells were further investigated by RNA sequencing and computational analyses. Results: These diabetic monkeys were characterized by early retinal vascular and neural damage and dyslipidemia. The typical acellular capillaries and pericyte ghost were found in the diabetic retina, which also exhibited reduced retinal nerve fiber layer thickness compared to controls (all P < 0.05). Of note, distinct sub-RPE drusenoid lesions were extensively observed in these diabetic monkeys (46.43% vs. 7.69%), and complements including C3 and C5b-9 were deposited in these lesions. RNA-seq analysis revealed complement activation, AGE/RAGE activation and inflammatory response in diabetic RPE cells. Consistently, the plasma C3 and C4 were particularly increased in the diabetic monkeys with drusenoid lesions (P = 0.028 and 0.029). Conclusions: The spontaneous type 2 diabetic monkeys featured with early-stage retinopathy including not only typical vascular and neural damage but also a distinct sub-RPE deposition. The complement activation of RPE cells in response to hyperglycemia might contribute to the deposition, revealing an unrecognized role of RPE cells in the early-stage pathological process of diabetic retinopathy.


Assuntos
Complemento C3/metabolismo , Complexo de Ataque à Membrana do Sistema Complemento/metabolismo , Retinopatia Diabética/metabolismo , Modelos Animais de Doenças , Epitélio Pigmentado da Retina/metabolismo , Animais , Ativação do Complemento , Diabetes Mellitus Tipo 2 , Retinopatia Diabética/diagnóstico , Dislipidemias/diagnóstico , Hiperglicemia/diagnóstico , Macaca fascicularis , Imagem Multimodal , Drusas Retinianas/diagnóstico , Epitélio Pigmentado da Retina/patologia , Vasos Retinianos/patologia
8.
Artigo em Inglês | MEDLINE | ID: mdl-33780342

RESUMO

Tracking the dynamic modules during cancer progression is essential for studying cancer pathogenesis, diagnosis and therapy. However, current algorithms only focus on detecting dynamic modules from temporal cancer networks without integrating the heterogeneous genomic data, thereby resulting in undesirable performance. To attack this issue, a novel algorithm (aka TANMF) is proposed to detect dynamic modules in cancer temporal attributed networks, which integrates the temporal networks and gene attributes. To obtain the dynamic modules, the temporality and gene attributed are incorporated into an overall objective function, which transforms the dynamic module detection into an optimization problem. TANMF jointly decomposes the snapshots at two subsequent time steps to obtain the latent features of dynamic modules, where the attributes are fused via regulations. Furthermore, L1 constraint is imposed to improve the robustness. Experimental results demonstrate that TANMF is more accurate than state-of-the-art methods in terms of accuracy. By applying TANMF to breast cancer data, the obtained dynamic modules are more enriched by the known pathways and associated with the survival time of patients. The proposed model and algorithm provide an effective way for the integrative analysis of heterogeneous omics.

9.
Schizophr Bull ; 47(3): 615-623, 2021 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-33159208

RESUMO

Exosomes have been suggested as promising targets for the diagnosis and treatment of neurological diseases, including schizophrenia (SCZ), but the potential role of exosome-derived metabolites in these diseases was rarely studied. Using ultra-performance liquid chromatography-tandem mass spectrometry, we performed the first metabolomic study of serum-derived exosomes from patients with SCZ. Our sample comprised 385 patients and 332 healthy controls recruited from 3 clinical centers and 4 independent cohorts. We identified 25 perturbed metabolites in patients that can be used to classify samples from patients and control participants with 95.7% accuracy (95% CI: 92.6%-98.9%) in the training samples (78 patients and 66 controls). These metabolites also showed good to excellent performance in differentiating between patients and controls in the 3 test sets of participants, with accuracies 91.0% (95% CI: 85.7%-96.3%; 107 patients and 62 controls), 82.7% (95% CI: 77.6%-87.9%; 104 patients and 142 controls), and 99.0% (95% CI: 97.7%-100%; 96 patients and 62 controls), respectively. Bioinformatic analysis suggested that these metabolites were enriched in pathways implicated in SCZ, such as glycerophospholipid metabolism. Taken together, our findings support a role for exosomal metabolite dysregulation in the pathophysiology of SCZ and indicate a strong potential for exosome-derived metabolites to inform the diagnosis of SCZ.


Assuntos
Exossomos/metabolismo , Metaboloma/fisiologia , Esquizofrenia/sangue , Esquizofrenia/diagnóstico , Adulto , Biomarcadores/metabolismo , Cromatografia Líquida , Feminino , Humanos , Masculino , Metabolômica , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem
10.
Cancer Cell Int ; 20(1): 569, 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33292221

RESUMO

BACKGROUND: Expression of the long non-coding mRNA LINC00152 has been reported to correlate with cancer cell resistance to oxaliplatin (L-OHP). However, little is known regarding the molecular mechanism of LINC00152 in esophageal cancer (EC). Hence, we intended to characterize the role of LINC00152 in EC, with a special focus on epithelial-mesenchymal transition (EMT) and L-OHP resistance. METHODS: We collected EC tissues and identified EC cell lines with higher L-OHP resistance, and then characterized expression patterns of LINC00152, Zeste Homologue 2 (EZH2), Zinc finger e-box binding homeobox (ZEB1) and EMT-related genes using RT-qPCR and Western blot analysis. Furthermore, their functional significance was identified by gain and loss-of-function experiments. The relationship among LINC00152, EZH2 and ZEB1 was examined using RIP, RNA pull-down and ChIP assays. Additionally, resistance of EC cells to L-OHP was reflected by CCK-8 assay to detect cell viability. Animal experiments were also conducted to detect the effects of the LINC00152/EZH2/ZEB1 on EMT and L-OHP resistance. RESULTS: LINC00152, EZH2 and ZEB1 were highly expressed in EC tissues and Kyse-150/TE-1 cells. As revealed by assays in vitro and in vivo, LINC00152 positively regulated ZEB1 expression through interaction with EZH2 to enhance EMT and L-OHP resistance in EC cells. In contrast, silencing of LINC00152 contributed to attenuated EMT and drug resistance of EC cells to L-OHP. CONCLUSIONS: Our study demonstrates that LINC00152/EZH2/ZEB1 axis can regulate EMT and resistance of EC cells to L-OHP, thus presenting a potential therapeutic target for EC treatment.

11.
J Cosmet Sci ; 71(3): 133-148, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33022209

RESUMO

Many outbreaks of Burkholderia cepacia complex (Bcc) infections are associated with contaminations in personal care products (PCPs). This study aimed to analyze a collection of Bcc isolates in PCPs and assess the susceptibility of preservatives, including dimethoxy dimethyl hydantoin (DMDMH), methylisothiazolinone-chloromethylisothiazolinone (MIT/cMIT), and methyl 4-hydroxybenzoate (MH). The Bcc isolates collected during the 3-year (2015-2017) study period were further examined by biochemical identification system, phylogenetic analysis based on recA nucleotide sequences, and multilocus sequence typing analysis. Preservatives susceptibility testing of Bcc bacteria were evaluated by minimum inhibitory concentration and minimum bactericidal concentration. A total of seven distinct sequence types (STs) were identified, which belonged to four different Bcc species: Burkholderia cenocepacia (ST621, ST258, and novel ST), Burkholderia lata (ST339 and ST336), Burkholderia contaminans (ST482), Burkholderia cepacia (ST922). For DMDMH and MH, the maximum permitted concentrations according to the safety specification of cosmetics (0.6% and 0.4%) were able to inhibit or kill all Bcc strains, but 40% of Bcc isolates could survive at higher than maximum permitted concentrations of MIT/cMIT (of a mixture in the ratio 3:1 of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one). The PCPs contamination of Bcc strains should be given more attention by manufacturers because of its diversity in molecular epidemiology and its low susceptibility to preservatives such as MIT/cMIT.


Assuntos
Complexo Burkholderia cepacia , Cosméticos , Técnicas de Tipagem Bacteriana , Burkholderia , Complexo Burkholderia cepacia/genética , Cosméticos/efeitos adversos , Epidemiologia Molecular , Filogenia
12.
Clin Transl Med ; 10(5): e189, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32997403

RESUMO

BACKGROUND: Dyslipidaemia contributes to the progression of coronary artery disease (CAD) toward adverse outcomes. Plasma lipidomic measure may improve the prognostic performances of clinical endpoints of CAD. Our research is designed to identify the correlations between plasma lipid species and the risks of death, major adverse cardiovascular event (MACE) and left ventricular (LV) remodeling in patients with CAD. METHODS: A total of 1569 Chinese patients with CAD, 1011 single-centre patients as internal training cohort, and 558 multicentre patients as external validation cohort, were enrolled. The concentration of plasma lipids in both cohorts was determined through widely targeted lipidomic profiling. Least absolute shrinkage and selection operator Cox and multivariate Cox regressions were used to develop prognostic models for death and MACE, respectively. RESULTS: Ten (Cer(d18:1/20:1), Cer(d18:1/24:1), PE(30:2), PE(32:0), PE(32:2), PC(O-38:2), PC(O-36:4), PC(16:1/22:2), LPC(18:2/0:0) and LPE(0:0/24:6)) and two (Cer(d18:1/20:1) and LPC(20:0/0:0)) lipid species were independently related to death and MACE, respectively. Cer(d18:1/20:1) and Cer(d18:1/24:1) were correlated with LV remodeling (P < .05). The lipidic panel incorporating 10 lipid species and two traditional biomarkers for predicting 5-year death risk represented a remarkable higher discrimination than traditional model with increased area under the curve from 76.56 to 83.65%, continuous NRI of 0.634 and IDI of 0.131. Furthermore, the panel was successfully used in differentiating multicentre patients with low, middle, or high risks (P < .0001). Further analysis indicated that the number of double bonds of phosphatidyl choline and the content of carbon atoms of phosphatidyl ethanolamines were negatively associated with death risk. CONCLUSIONS: Improvement in the prediction of death confirms the effectiveness of plasma lipids as predictors to risk classification in patients with CAD. The association between the structural characteristics of long-chain polyunsaturated fatty acids and death risk highlights the need for mechanistic research that characterizes the role of individual lipid species in disease pathogenesis.

13.
Front Neurosci ; 14: 823, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32982663

RESUMO

Oxidative stress has been suggested to play a key role in multiple sclerosis (MS), but clinical data on oxidative stress markers in MS patients were inconsistent. This study sought to quantitatively summarize the data of oxidative stress markers in the blood and cerebrospinal fluid (CSF) of patients with MS in the literature. We conducted a systematic search of PubMed and Web of Science and included studies if they provided data on the concentrations of oxidative stress markers in the peripheral blood and CSF of MS patients and healthy control (HC) subjects. The systematic search resulted in the inclusion of 31 studies with 2,001 MS patients and 2,212 HC subjects for meta-analysis. Random-effects meta-analysis demonstrated that patients with MS had significantly increased concentrations of blood oxidative stress markers compared with HC subjects for malondialdehyde (MDA; Hedges' g, 2.252; 95% CI, 1.080 to 3.424; p < 0.001) and lipid hydroperoxide by tert-butyl hydroperoxide-initiated chemiluminescence (CL-LOOH; Hedges' g, 0.383; 95% CI, 0.065 to 0.702; p = 0.018). In contrast, concentrations of albumin (Hedges' g, -1.036; CI, -1.679 to -0.394; p = 0.002) were significantly decreased in MS patients when compared with those in HC subjects. However, the other analyzed blood oxidative stress markers did not show significant differences between cases and controls. Furthermore, this meta-analysis showed significant association between CSF MDA and MS (Hedges' g, 3.275; 95% CI, 0.859 to 5.691; p = 0.008). Taken together, our results revealed increased blood and CSF MDA and decreased blood albumin levels in patients with MS, strengthening the clinical evidence of increased oxidative stress in MS.

14.
Angew Chem Int Ed Engl ; 59(46): 20470-20474, 2020 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-32748527

RESUMO

The gold-catalyzed intermolecular oxyarylation of alkenes is reported. This work employed the oxidative addition of aryl iodides to Me-DalphosAu+ for the formation of a AuIII -Ar intermediate. The better binding ability of alkenes over O nucleophiles ensured the success of intermolecular oxyarylation, giving desired products with a broad substrate scope and high efficiency (>50 examples with up to 95 % yield). One-pot converting of methoxy groups into other nucleophiles allowed achieving alkene difunctionalization with the construction of C-N, C-S, and C-C bonds under mild conditions.


Assuntos
Alcenos/química , Ouro/química , Catálise , Estrutura Molecular , Oxirredução , Estereoisomerismo
15.
J Exp Clin Cancer Res ; 39(1): 131, 2020 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-32653028

RESUMO

BACKGROUND: Esophageal cancer (EC) represents one of the most aggressive digestive neoplasms globally, with marked geographical variations in morbidity and mortality. Chemoprevention is a promising approach for cancer therapy, while acquired chemoresistance is a major obstacle impeding the success of 5-fluorouracil (5-FU)-based chemotherapy in EC, with the mechanisms underlying resistance not well-understood. In the present study, we focus on exploring the role of long non-coding RNA (lncRNA) HOTAIR in EC progression and sensitivity of EC cells to 5-FU. METHODS: Paired cancerous and pre-cancerous tissues surgically resected from EC patients were collected in this study. Promoter methylation of the MTHFR was assessed by methylation-specific PCR. RIP and ChIP assays were adopted to examine the interaction of DNA methyltransferases (DNMTs) with lncRNA HOTAIR and MTHFR, respectively. EC cells resistant to 5-FU were induced by step-wise continuous increasing concentrations of 5-FU. The sensitivity of EC cells to 5-FU in vivo was evaluated in nude mice treated with xenografts of EC cells followed by injection with 5-FU (i.p.). RESULTS: We found reciprocal expression patterns of lncRNA HOTAIR and MTHFR in EC tissues and human EC cells. Interference with lncRNA HOTAIR enhanced 5-FU-induced apoptosis, exhibited anti-proliferative activity, and reduced promoter methylation of the MTHFR in EC cells. Besides, overexpression of MTHFR attenuated the acquired chemoresistance induced by overexpression of lncRNA HOTAIR in EC cells. At last, enhanced chemosensitivity was observed in vivo once nude mice xenografted with lncRNA HOTAIR-depleted EC cells. CONCLUSION: Together, our study proposes that pharmacologic targeting of lncRNA HOTAIR sensitizes EC cells to 5-FU-based chemotherapy by attenuating the promoter hypermethylation of the MTHFR in EC.


Assuntos
Metilação de DNA , Resistencia a Medicamentos Antineoplásicos , Neoplasias Esofágicas/tratamento farmacológico , Fluoruracila/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , RNA Longo não Codificante/genética , Animais , Antimetabólitos Antineoplásicos/farmacologia , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Proliferação de Células , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Humanos , Metilenotetra-Hidrofolato Redutase (NADPH2)/química , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Prognóstico , Regiões Promotoras Genéticas , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Cureus ; 12(5): e8339, 2020 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-32617214

RESUMO

Intravenous unfractionated heparin (UFH) remains one of the most commonly used anticoagulants in the hospital setting. The optimal protocol for initiation and maintenance of UFH has been difficult to determine. Over the past two decades, weight-based nomogram protocols have gained favor. Herein, we present a retrospective study of 377 patients at a single tertiary academic center treated with low intensity (LI) and standard intensity (SI) UFH protocols for therapeutic anticoagulation. UFH levels are measured by anti-Xa assay activity with therapeutic levels of 0.30 to 0.70 IU/mL for SI and 0.25 to 0.35 IU/mL for LI.  Patients treated on the LI protocol were more likely to have had a previous history of bleeding and lower baseline hemoglobin. Incidence of new or worsening thrombus while on UFH was comparable between both protocols (odds ratio (OR) 0.93, 95% confidence interval (CI) 0.29-2.98, p=0.899). Patients on LI protocol had higher incidence of bleeding while on UFH (OR 1.21, 95% CI 0.51-2.89, p=0.667). Our study thus suggests that the LI protocol may have comparable efficacy to the SI protocol in treating venous thromboembolism (VTE) and that target anti-Xa levels of 0.25 to 0.35 IU/mL may be more optimal in high-risk patients.

17.
Clin Transplant ; 34(3): e13797, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31997402

RESUMO

Postautologous stem cell transplantation (ASCT) engraftment syndrome (ES) is a well-known clinical complication; however, many aspects remain largely controversial. In this retrospective study, we reviewed records of 156 ASCTs done over 2 years in our institution. Our results show that 45 (34 multiple myeloma/amyloidosis and 11 lymphoma) of 156 adult patients (29%) were diagnosed with ES. Patients with ES were significantly more likely to have fever, rash, and diarrhea upon engraftment. Risk factors for ES included shorter time from diagnosis to ASCT (P = .029), and lower number of pretransplant treatment regimens (0.012). Post-ASCT, patients with ES had significantly lower absolute lymphocyte count on first engraftment day (P = .014). Most ES patients received treatment with steroids. Initial dose of prednisone/methylprednisolone was 2 mg/kg (n = 34), 1 mg/kg (n = 7), while four patients received 1000 mg IV with median length of therapy 7.5 days. One ES patient with inadequate steroid therapy died of ES complications, while another developed respiratory failure requiring intubation but had full recovery with steroids treatment. In conclusion, patients with shorter time from diagnosis to ASCT and with less prior therapy are more likely to develop ES. Overall survival of ES patients has improved with greater awareness of the diagnosis and earlier use of steroids.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Adulto , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Retrospectivos , Transplante de Células-Tronco , Transplante Autólogo , Resultado do Tratamento
18.
RSC Adv ; 10(69): 42340-42348, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-35516740

RESUMO

In this study, we designed a simple procedure for the synthesis of fungus-derived biomass porous carbon (FBPC), which was further used to prepare a MnO2@FBPC composite by a hydrothermal method. The MnO2@FBPC nanocomposite showed a porous structure, large specific surface area, and high conductivity, and was modified on the carbon ionic liquid electrode (CILE) to obtain a working electrode for the sensitive voltammetric determination of rutin. The electrochemical response of rutin was studied via cyclic voltammetry with electrochemical parameters calculated. Under the optimal conditions, the linear range for the rutin analysis was obtained by the differential pulse voltammetry from 0.008 to 700.0 µmol L-1 with the detection limit of 2.67 nmol L-1 (3σ). This MnO2@FBPC/CILE was applied to directly detect the rutin concentration in drug and human urine samples with satisfactory results.

19.
Am J Cancer Res ; 9(10): 2233-2248, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31720085

RESUMO

Esophageal cancer (EC) is one of the most common malignancies in the world. The currently used chemotherapeutic drug for the treatment of EC is paclitaxel (PTX), the efficacy of which is affected by the development of drug resistance. The present study aims to define the role of the long noncoding RNA (lncRNA) DDX11-AS1 in the progression of EC with the involvement of PTX-resistant EC cells. First, EC and adjacent normal tissue samples were collected from 82 patients with EC, after which the expression levels of DDX11-AS1, TOP2A and TAF1 were determined. The results showed that DDX11-AS1, TOP2A and TAF1 were highly expressed in EC tissues, and there was a positive correlation between the expression levels of DDX11-AS1 and TOP2A. A PTX-resistant EC cell line was constructed. Next, we evaluated the effects of DDX11-AS1 and TOP2A on the resistance of EC cells to PTX, and the regulatory relationships between DDX11-AS1, TOP2A and TAF1 were investigated. DDX11-AS1 could promote TOP2A transcription via TAF1, and the knockdown of TOP2A or DDX11-AS1 could increase the sensitivity of EC cells to PTX. The effect of DDX11-AS1 on the growth of PTX-inhibited tumors was confirmed using a tumor formation assay in nude mice. It was verified that knocking down DDX11-AS1 reduced the expression level of TOP2A and inhibited tumor growth. In conclusion, our findings suggest that DDX11-AS1 knockdown results in reduced resistance of EC cells to PTX by inhibiting TOP2A transcription via TAF1. Therefore, DDX11-AS1 knockdown could be a promising therapeutic strategy for EC.

20.
Mikrochim Acta ; 186(12): 783, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31732804

RESUMO

Porous carbon was prepared from wheat flour by alkali treatment and carbonization. The resulting biomass-derived porous carbon (BPC) was employed to prepare a Pt-Au-BPC nanocomposite by a hydrothermal method. The material was then placed on the surface of a carbon ionic liquid electrode (CILE). The Pt-Au-BPC was characterized by SEM, XPS, and the modified CILE by electrochemical methods. They revealed a porous structure, a large specific surface with high conductivity. Pt-Au-BPC/CILE was applied to the sensitive determination of quercetin. Electrochemical response was studied by cyclic voltammetry and differential pulse voltammetry (DPV). Under optimized experimental conditions, the oxidation peak current (measured at 0.48 V vs. Ag/AgCl by DPV) increases linearly in the 0.15 to 6.0 µM and in the 10.0 to 25.0 µM quercetin concentration range. The detection limit is 50.0 nM (at 3σ). The Pt-Au-BPC/CILE was applied to the direct determination of quercetin in ginkgo tablets sample and gave satisfactory results. Graphical abstract A Pt-Au-BPC nanocomposite modified carbon ionic liquid electrode was applied to differential pulse voltammetric determination of quercetin. BPC: biomass-derived porous carbon.


Assuntos
Carbono/química , Nanocompostos/química , Quercetina/análise , Biomassa , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Eletrodos , Farinha , Ginkgo biloba/química , Ouro/química , Líquidos Iônicos/química , Limite de Detecção , Nanopartículas Metálicas/química , Platina/química , Porosidade , Compostos de Piridínio/química , Reprodutibilidade dos Testes , Comprimidos/análise , Triticum/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...