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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 137-144, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33554810

RESUMO

OBJECTIVE: To investigate the short-term efficacy and safety of generic bortezomib in the treatment of Chinese patients with multiple myeloma (MM). METHODS: Clinical data of 62 MM patients (median age of 62 years) who had accepted at least 2 cycles of chemotherapy based on generic bortezomib in our center from December 2017 to July 2019 were retrospectively analyzed, including 47 newly diagnosed patients and 15 with disease recurrence or progression. RESULTS: Anemia, renal dysfunction, hypoproteinemia and high level of ß 2-microglobulin were all improved rapidly after induction treatment. In 56 patients who had completed at least 4 cycles of chemotherapy, the overall response rate (ORR) was 85.7%, and 64.3% of the patients achieved very good partial response (VGPR) or better, and 28.6% achieved complete remission (CR) or better. In the 19 patients who had already completed all planned induction and consolidation treatment (9 cycles of chemotherapy or 4-6 cycles of chemotherapy plus autologous hematopoietic stem cell transplantation), 84.2% achieved VGPR or better, and 57.9% achieved CR or stringent complete remission (sCR). Median follow-up time was 300 days with data cut-off date of September 20, 2019, and the progression-free survival (PFS) rate and overall survival (OS) rate were 62.1% and 85.3%, respectively. The possible adverse reactions associated with bortezomib were grade 1-2, the most common hematologic adverse reaction was thrombocytopenia (27.4%), and the most common non-hematologic adverse reaction was peripheral neuropathy (43.5%), followed by asthenia (37.1%). CONCLUSION: The disease severity can be rapidly alleviated after generic bortezomib-based chemotherapy, and a favorable short-term efficacy and survival have been observed with a generally acceptable toxicity profile. However, the long-term outcomes will be examined through further follow-up.


Assuntos
Mieloma Múltiplo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/uso terapêutico , Dexametasona/uso terapêutico , Intervalo Livre de Doença , Humanos , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Recidiva Local de Neoplasia , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento
2.
Chemosphere ; 274: 129739, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33529949

RESUMO

To our knowledge, little evidence is available about effects of aircraft noise (AN), a non-chemical stressor, on cognitive function. Again, it is unknown whether or not the heat stress (HS)-induced cognitive deficits can be exacerbated by AN. The adult male mice were assigned to four groups: group 1 mice exposed to non-HS (24-26 °C 2 h daily for 4 consecutive days) and white noise (WN) (2 h daily for 4 consecutive days), group 2 mice exposed to WN and HS (32-34 °C 2 h daily for 4 consecutive days), group 3 mice exposed to AN and non-HS (2 h daily for 4 consecutive days) and group 4 mice exposed to AN and HS (2 h daily for consecutive 4 days). Cognitive function were determined by passive avoidance, Y-maze, Morris water maze, and novel object recognition tests. Gut barrier and blood-brain-barrier (BBB) permeability, upload of lipopolysaccharide (LPS) translocation, systemic and central inflammation, and stress reactions were examined. Heat stressed mice displayed both increased stress reactions and learning and memory loss. Heat stress also caused gut barrier hyperpermeability, increased upload of LPS translocation, systemic inflammation, BBB disruption and hippocampal neuroinflammation. Aircraft noise stressed mice did not display systemic inflammation but caused gut barrier hyperpermeability, increased upload of LPS translocation, increased stress reactions, BBB disruption, hippocampal neuroinflammation and cognitive deficits. Aircraft noise exposure further exacerbated the heat stress-induced cognitive deficits and its complications. Our data suggest that AN, like HS, causes cognitive impairments via similar mechanisms in male mice.

3.
EBioMedicine ; 62: 103126, 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33232873

RESUMO

BACKGROUND: The high heterogeneity of acute myeloid leukaemia (AML) reflected in the patient- and disease-related factors accounts for the unsatisfactory prognosis despite the introduction of novel therapeutic approaches and drugs in recent years. METHODS: In the development set (n = 412), parameters including age, hematopoietic cell transplantation-comorbidity index, white blood cell count, hemoglobin, biallelic CEBPA mutations, DNMT3A mutations, FLT3-ITD/NPM1 status, and ELN cytogenetic risk status were identified as independent prognostic factors for overall survival (OS) in the multivariable Cox regression analysis. A nomogram combining these predictors for individual risk estimation was established thereby. FINDINGS: The prognostic model demonstrated promising performance in the development cohort. The calibration plot, C-index (0.74), along with the 1-, 2- and 3-year area under the receiver operating characteristic curve (AUC, 0.76, 0.79, and 0.74, respectively) in the validation set (n = 238) substantiated the robustness of the model. In addition to stratifying young (age ≤ 60 years) and elderly patients (age > 60 years) into three and two risk groups with significant distinct outcomes, the prognostic model succeeded in distinguishing eligible candidates for hematopoietic stem cell transplantation. INTERPRETATION: The prognostic model is capable of survival prediction, risk stratification and helping with therapeutic decision-making with the use of easily acquired variables in daily clinical routine. FUNDING: This work was supported in part by grants from the National Natural Science Foundation of China (81770141), the National Key R&D Program of China (2016YFE0202800), and Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20161406).

4.
Inflammopharmacology ; 28(6): 1553-1566, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32959092

RESUMO

We aimed to elucidate the role of cortical and hippocampal dendritic spines on neurological deficits associated with hippocampal microgliosis, hippocampal neurogenesis, and neuroinflammation in mice with cortical compact impact (CCI) injury. In the present study, we found that CCI reduced spatial memory mean latency (10 s. vs 50 s) and motor dysfunction (130 s. vs 150 s.) in mice, as determined by Morris water maze and rotarod test, respectively. Golgi staining of cortical pyramidal neurons revealed that, compared to the controls, the CCI group treated with vehicle solution had significantly lower values of dendritic order (or dendritic branch number) (4.0 vs 6.2), total spine length (400 µm vs 620 µm) and spine density (40 spines/µm vs 60 spines/µm), but had significantly higher values of dendritic beading (40 beadings/mm vs 20 beadings/mm). Additionally, Sholl analysis showed that, compared to controls, the CCI + NS group mice had significantly lower values of dendritic intersections (1.0 vs 2.0). Immunofluorescence assay also revealed that, compared to controls, the CCI + NS group mice had significantly higher values of the newly formed hippocampal cells (1250/mm2 vs 1000/mm2) but significantly lower values of dendritic order (2.0 branch # vs 4.2 branch #), total spine length (180 µm vs 320 µm) and intersection (1.0 vs 3.0). The CCI + NS group mice further showed significantly higher numbers of microglia in the dentate gyrus of the hippocampus and higher concentrations of pro-inflammatory cytokines in the cerebrospinal fluids. All the CCI-induced spatial memory (40 s) and motor (150 s) dysfunction, deranged dendritic and spine morphology of cortical pyramidal neurons or hippocampal newly formed cells, hippocampal microgliosis, and central neuroinflammation were all significantly reduced by melatonin administration during post-CCI. Simultaneously, melatonin therapy caused an enhancement in the compensatory hippocampal neurogenesis and neurotrophic growth factors (e.g., doublecortin-1) and compensatory central anti-inflammatory cytokines. Our results indicate that melatonin attenuates the spatial memory and motor deficits via the modification of cortical and hippocampal dendritic spine morphology, hippocampal microgliosis and neurogenesis, and neuroinflammation in mice with traumatic brain injury.

5.
3 Biotech ; 10(8): 346, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32728513

RESUMO

In the current study, we report the high-quality draft genome sequence of Neonectria sp. DH2, an endophytic fungus isolated from Meconopsis grandis Prain in Tibet. The whole genome is about 45.8 Mbp, with a GC content of 53%. A total of 14,163 genes are predicted to encode proteins, and 557 of them are considered as unique, as no matches are found in five gene databases. A neighbor-joining phylogenetic tree based on internal transcribed spacer (ITS) region sequences shows that Neonectria sp. DH2 was most closely related to Neonectria ramulariae. 47 biosynthetic gene clusters (BGC) were identified in Neonectria sp. DH2 genome, and only 5 BGCs shows significant similarities to previously reported BGCs. The presence of 42 unique BGCs in Neonectria sp. DH2 suggests that it has great potential to produce novel secondary metabolites.

6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(3): 833-841, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32552944

RESUMO

OBJECTIVE: To investigate the effects of high dose vitamin C on proliferation and apoptosis of acute myeloid leukemia (AML) cell lines including HL-60, U937 and primary CD34+ leukemia cells in AML. METHODS: CD34+ cells were sorted by using immunomagnetic cell sorting system, then the primary CD34+ leukemia cells, including HL-60 and U937 cell lines were cultured in vitro. Cells in each group were treated with different concentrations of vitamin C, the survival rate of cells was determined by MTT assay, the apoptosis rate of cells was evaluated by Annexin V/PI double staining, the expression of apoptotic proteins-including cleaved caspase 3, cleaved caspase-9 and cleaved PARP were detected by Western blot. RESULTS: The proliferation of HL-60 and U937 cells could be inhibited by high dose vitamin C, which showed a concentration-dependent manner (r=-0.9664; r=-0.9796). HL-60 and U937 cells were treated with different concentrations of vitamin C (8 and 20 mmol/L) for 24 hours, respectively, it was found that with the increasing of vitamin C concentration, cell apoptosis rate was significantly increased (r=0.9905; r=0.9971), and the expression of apoptosis related proteins including cleaved caspase 3, cleaved caspase-9 and cleaved PARP was aslo significantly increased with the increasing of concentration. In addition, it was found that with or without the mutation of TET2, high dose vitamin C could inhibit the proliferation (r=-0.9719; r=-0.9699) and promote the apoptosis (r=0.9998; r=0.9901) of primary CD34+ leukemia cells in AML, which showed a dose-dependent manner, but it showed no effect on the proliferation (r=-0.2032) and apoptosis (r=0.1912) of normal CD34+ cells. CONCLUSION: High dose vitamin C can inhibit the proliferation and promote the apoptosis of acute myeloid leukemia cells, and selectively kill primary CD34+ leukemia cells in AML.


Assuntos
Apoptose , Leucemia Mieloide Aguda , Ácido Ascórbico , Proliferação de Células , Células HL-60 , Humanos , Células U937
7.
Biomed Pharmacother ; 127: 110194, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32371315

RESUMO

BACKGROUND: Heat stroke-induced mortality is rising across the globe. So, the design of prophylactic and/or therapeutic modalities for heat stroke is pressing need. The common plant derived flavonoid exhibits strong anti-oxidant and anti-inflammatory activities; however, its effects in heat stroke remain unknown. The study aimed to investigate the cardioprotective effects of myricetin on heat stroke induced acute myocardial injury as well as lethality in rats and to explore the underlying mechanisms. METHODS: Myocardial injury was induced by subjecting the anesthetized rats to a high ambient temperature of 43 °C for 70 min. An intragastrical dose of myricetin (5-25 mg/kg body weight) was given to rats once per day for one week prior to the start of heat stress. Heat shock protein 72 antibodies was given intraperitoneally to rats 24 h before the start of heat stress. Myocardial injury severity was estimated by determing myocardial damage scores, myocardial injury indicators, myocardial oxidative and inflammatory factors. Western blot analysis was used for cardiac expression of heat shock protein (HSP)72. RESULTS: Significant (P < 0.05) up-regulation of HSP-72 after chronic administration of myricetin coincided with significant (P < 0.05) reduction in hyperthermia, hypotension, cardiac inflammatory and oxidative damage and lethality. Inhibition of HSP-72 showed a significant (P < 0.05) reversal in the cardiaprotection as well as survival. CONCLUSIONS: Our results indicate that myricetin diminishes myocardial injury as well as lethality in heat stroke by up-regulating HSP-72 and show promise as a novel prevention therapeutic for heat stroke.

8.
J Ovarian Res ; 13(1): 45, 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-32334623

RESUMO

OBJECTIVE: Currently, the function and mechanisms of long non-coding RNAs (lncRNAs) involved in the metastasis of epithelial ovarian cancer (EOC), especially those of the lncRNAs participated in the epithelial-mesenchymal transition (EMT) process, remains largely unknown. Here, we focused on a lncRNA named AOC4P and analysed its role in EOC. MATERIALS AND METHODS: The expression of AOC4P gene was examined with quantitative real-time quantitative PCR (qRT-PCR). The cell migration and invasion were detected by Transwell and scratch assays. The in vivo metastatic activity was evaluated by intraperitoneal metastasis model. The downstream genes were investigated by a tumour EMT real-time polymerase chain reaction (RT-PCR) array, and validated by qRT-PCR and Western blot. RESULTS: The results showed that AOC4P expression levels were decreased in EOC tissues and cell lines, and that the under-expression of AOC4P was positively correlated with FIGO stage and lymph node metastasis. Furthermore, the knockdown of AOC4P expression in poorly metastatic EOC cell lines remarkably facilitated cell migration/invasion while the overexpression of AOC4P in highly metastatic EOC cell lines reduced the metastatic ability of these cells in vitro. Consistently, the anti-metastatic role of AOC4P in vivo was also verified by bioluminescence imaging and tumour dissection. Mechanistically, the anti-metastatic effect of AOC4P in EOC was partially mediated by the EMT process accompanied by the alterations in MMP9 and COL1A2 expression. CONCLUSION: These data highlight that AOC4P plays a critical role in EOC invasion/metastasis and could function as a novel and effective target for the lncRNA-based anti-metastatic clinical management of EOC.

9.
Metab Brain Dis ; 35(6): 1017-1034, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32240489

RESUMO

Atherosclerosis has been associated with the progression of cognitive impairment and the effect of metabolic changes in the brain on cognitive function may be pronounced. The aim is to reveal the metabolic changes during atherosclerosis and clarify the possible role of exercise in regulating hippocampal metabolism. Hence, A rat model of atherosclerosis was established by high-fat diet feeding in combination with vitamin D3 intraperitoneal injection, then 4 weeks of aerobic exercise was conducted. Metabolomics based on GC-MS was applied to detect small molecules metabolites and western blot was used to detect the concentration of enzymes involved in metabolic changes in rat hippocampus. Compared to the control group, metabolites including xylulose 5-phosphate, threonine, succinate, and nonanoic acid were markedly elevated, whereas methyl arachidonic acid and methyl stearate decreased in the AS group, accompanied by a raised concentration of aldose reductase and glucose 6-phosphate dehydrogenase as well as a declined concentration of acetyl-CoA carboxylase and fatty acid synthase. After 4 weeks' aerobic exercise, the levels of succinic acid, branched chain amino acids, nonanoic acid, desmosterol, and aldose reductase decreased, whereas methyl arachidonic acid, methyl stearate, and glyceraldehyde-3-phosphate elevated in the hippocampus of the TAS group in comparison with the AS group. These results suggest that atherosclerosis could cause a severe metabolic disturbance, and aerobic exercise plays an important role in regulating atherosclerosis-induced disorder of glucose metabolism in the hippocampus.

10.
J Vis Exp ; (157)2020 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-32281968

RESUMO

Incomplete spinal cord injury (SCI) often leads to impairments of sensorimotor functions and is clinically the most frequent type of SCI. Human Brown-Séquard syndrome is a common type of incomplete SCI caused by a lesion to one half of the spinal cord which results in paralysis and loss of proprioception on the same (or ipsilesional) side as the injury, and loss of pain and temperature sensation on the opposite (or contralesional) side. Adequate methodologies for producing a spinal cord lateral hemisection (HX) and assessing neurological impairments are essential to establish a reliable animal model of Brown-Séquard syndrome. Although lateral hemisection model plays a pivotal role in basic and translational research, standardized protocols for creating such a hemisection and assessing unilateralized function are lacking. The goal of this study is to describe step-by-step procedures to produce a rat spinal lateral HX at the 9th thoracic (T9) vertebral level. We, then, describe a combined behavior scale for HX (CBS-HX) that provides a simple and sensitive assessment of asymmetric neurological performance for unilateral SCI. The CBS-HX, ranging from 0 to 18, is composed of 4 individual assessments which include unilateral hindlimb stepping (UHS), coupling, contact placing, and grid walking. For CBS-HX, the ipsilateral and contralateral hindlimbs are assessed separately. We found that, after a T9 HX, the ipsilateral hindlimb showed impaired behavior function whereas the contralateral hindlimb showed substantial recovery. The CBS-HX effectively discriminated behavioral functions between ipsilateral and contralateral hindlimbs and detected temporal progression of recovery of the ipsilateral hindlimb. The CBS-HX components can be analyzed separately or in combination with other measures when needed. Although we only provided visual descriptions of the surgical procedures and behavioral assessments of a thoracic HX, the principle may be applied to other incomplete SCIs and at other levels of the injury.


Assuntos
Traumatismos da Medula Espinal/fisiopatologia , Medula Espinal/cirurgia , Animais , Comportamento Animal , Modelos Animais de Doenças , Masculino , Ratos , Medula Espinal/patologia
11.
Nutr Metab (Lond) ; 17: 26, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32256674

RESUMO

Background: Androgen receptor (AR) has been reported to play vital roles in exercise-induced increase of muscle mass in rats, but needs to be further verified and the mechanism behind remains unclear. As AR target genes, insulin growth factor-1 (IGF-1) and IGF-1 receptor (IGF-1R) promote muscle hypertrophy through activating PI3K/Akt- mammalian target of rapamycin (mTOR) pathway, a classic pathway of muscle hypertrophy. So the main purpose of this study was using AR antagonist flutamide to demonstrate AR's effect on training-induced muscle hypertrophy and its possible mechanism: IGF-1/IGF-1R- PI3K/Akt- mTOR pathway? Methods: Forty-eight Sprague Dawley male rats aged 7 weeks were randomly divided into six groups: control (C), flutamide (F), resistance training (R), resistance training plus flutamide (R + F), endurance training (E), and endurance training plus flutamide (E + F) groups. Flutamide was used to block AR in rats. Rats in R and R + F groups fulfilled 3 weeks of ladder climbing with progressively increased load, while E and E + F rats completed 3-week moderate intensity aerobic exercise on a treadmill. The relative muscle mass (muscle mass/body weight) of rats was detected. Serum levels of testosterone and IGF-1 of rats were determined by ELISA, and mRNA levels of IGF-1R and mTOR in muscles by real-time PCR. Protein levels of AR, IGF-1, IGF-1R, mTOR, PI3K, Akt, p-PI3K and p-Akt in muscles were detected by Western blot. Results: (1) The training-induced rise in the relative muscle mass and the expression levels of AR were only found in the gastrocnemius of R rats and in the soleus of E rats (selective muscle hypertrophy), which were blocked by flutamide. (2) Serum testosterone in the R and E rat were increased, and flutamide exerted no effect. (3) The levels of IGF-1, IGF-1R and mTOR as well as the activities of PI3K and Akt were enhanced selectively (in the gastrocnemius of R rats and in the soleus of E rats), which were reduced by flutamide. Conclusions: AR exerted an essential role in both resistance training and endurance training-induced muscle hypertrophy, which was mediated at least partly through IGF-1/IGF-1R- PI3K/Akt- mTOR pathway.

12.
Cancer Med ; 9(7): 2299-2308, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32017467

RESUMO

BACKGROUND: Brain metastases are one of the most common intracranial neoplasms. Increasing evidence have indicated that systemic immunotherapy may provide long-term benefits for brain metastases. Herein, we presented the results of an immune oncology panel RNA sequencing platform for patients with brain metastases from different primary sites. METHODS: We investigated 25 samples of human brain metastases from lung cancer (n = 12), breast cancer (n = 6), and colorectal cancer (n = 7). Besides, 13 paired samples of adjacent noncancerous brain tissue (10 from patients with lung cancer and 3 from patients with breast cancer) were collected as controls. By comparing the brain metastases and paired samples of adjacent noncancerous brain tissue from 13 patients, we detected three upregulated and six downregulated genes, representing the malignant properties of cancer cells and increased immune infiltration in the microenvironment. Next, we profiled the immune-related genes in brain metastases from three primary cancer types. RESULTS: A group of genes were significantly overexpressed in the microenvironment of brain metastases from lung cancer, covering the checkpoint pathways, lymphocyte infiltration, and TCR-coexpression. Especially, immune checkpoint molecules, PD-L1, PD-L2, and IDO1 were expressed at higher levels in brain metastases from lung cancer than those from the other two cancer types. CONCLUSIONS: This study presents an immune landscape of brain metastases from different cancer types. With high RNA expression levels of PD-1/PD-L1 axis and immune infiltration in brain metastases, it would be worthwhile to explore the efficacy of immune checkpoint blockade for lung cancer patients with intracranial metastases.

13.
Int J Cancer ; 146(9): 2588-2598, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31577838

RESUMO

Peritoneal metastasis is a critical feature and clinical challenge in epithelial ovarian cancer (EOC). We previously identified a novel long noncoding RNA (lncRNA, TC0101441) in epithelial ovarian cancer (EOC) using microarrays. However, the impact of TC0101441 on EOC metastasis and prognosis remains unclear. TC0101441 expression in EOC tissues and its correlation with clinicopathological factors and prognosis were examined. A series of in vitro and in vivo assays were performed to elucidate the roles and mechanism of TC0101441 in EOC metastasis. We found that TC0101441 levels were elevated in EOC tissues compared with those in normal controls and significantly correlated with an advanced clinical stage and lymph node metastasis. TC0101441 was determined to be an independent prognostic predictor of overall survival (OS) and disease-free survival (DFS). Furthermore, loss-of-function assays showed that TC0101441 promoted the invasive and metastatic capacities of EOC cells both in vitro and in vivo. Mechanistically, the prometastatic effects of TC0101441 were linked to the induction of epithelial-mesenchymal transition (EMT). Importantly, KiSS1 was identified as a downstream target gene of TC0101441 and was downregulated by TC0101441 in EOC cells. After TC0101441 was silenced, the corresponding phenotypes of EOC cell invasion and EMT were reversed by the overexpression of KiSS1. Taken together, our data suggest that TC0101441 functions as a potential promigratory/invasive oncogene by promoting EMT and metastasis in EOC through downregulation of KiSS1, which may represent a novel prognostic marker and therapeutic target in EOC.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Epitelial do Ovário/patologia , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Kisspeptinas/metabolismo , Neoplasias Peritoneais/secundário , RNA Longo não Codificante/genética , Animais , Apoptose , Biomarcadores Tumorais/genética , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/metabolismo , Movimento Celular , Proliferação de Células , Feminino , Humanos , Kisspeptinas/genética , Metástase Linfática , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/metabolismo , Prognóstico , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Ultrason Sonochem ; 61: 104850, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31698197

RESUMO

As a novel type of carbon materials, graphynes possesses the merits of high carrier mobility and large surface areas, etc. However, to date, the main research of graphynes is focused on theoretical calculation whereas few strategies have been reported for the fabrication of graphynes. In this work, a facile method named ultrasound-promoted synthesis was developed to fabricate γ-graphyne using PhBr6 and CaC2 as the raw materials. The reaction system in argon atmosphere ultrasonically vibrated for 24 h in the ultrasonic bath at a power of 180 W and frequency of 53 kHz. The structure, morphology, and component of the obtained samples were detected by X-ray diffraction, Raman spectroscopy, X-ray photoelectron spectroscopy, FT-IR spectra, scanning electron microscopy, transmission electron microscopy, and the selected area electron diffraction. The electrochemical and photoelectrochemical measurements indicate that γ-graphyne can be used as superior electrode mateirals in supercapacitor and photoelectrochemical catalysis. From the results of galvanostatic charge/discharge measurements, the γ-graphyne supercapacitor delivers a maximum specific capacitance of 81 F/g at 0.2 A/g and a capacitance retention rate of 87.5% after 5000 cycles at 3 A/g. Moreover, UV-vis light photoelectrochemical response and high carrier density are observed for γ-graphyne. It is also demonstrated that the charge-transfer resistance is low by Tafel slopes and Nyquist plots. This work puts forward a new and facile strategy for the fabrication of γ-graphyne and explores its application in the field of solar energy conversion and storage.

15.
BMC Genomics ; 20(1): 831, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703614

RESUMO

BACKGROUND: Formalin-fixed and paraffin-embedded (FFPE) blocks held in clinical laboratories are an invaluable resource for clinical research, especially in the era of personalized medicine. It is important to accurately quantitate gene expression with degraded and small amounts of total RNA from FFPE materials. RESULTS: High concordance in transcript quantifications were shown between FF and FFPE samples using the same kit. The gene expression using the TaKaRa kit showed a difference with other kits, which may be due to the different principle of rRNA depletion or the amount of input total RNA. For seriously degraded RNA from FFPE samples, libraries could be constructed with as low as 50 ng of total RNA, although there was residual rRNA in the libraries. Data analysis with HISAT demonstrated that the unique mapping ratio, percentage of exons in unique mapping reads and number of detected genes decreased along with the decreasing quality of input RNA. CONCLUSIONS: The method of RNA library construction with rRNA depletion can be used for clinical FFPE samples. For degraded and low-input RNA samples, it is still possible to obtain repeatable RNA expression profiling but with a low unique mapping ratio and high residual rRNA.


Assuntos
Formaldeído , Inclusão em Parafina , Estabilidade de RNA , RNA Ribossômico/genética , Análise de Sequência de RNA/métodos , Fixação de Tecidos
16.
EBioMedicine ; 48: 478-490, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31628020

RESUMO

BACKGROUND: Urea, the end product of protein metabolism, has been considered to have negligible toxicity for a long time. Our previous study showed a depression phenotype in urea transporter (UT) B knockout mice, which suggests that abnormal urea metabolism may cause depression. The purpose of this study was to determine if urea accumulation in brain is a key factor causing depression using clinical data and animal models. METHODS: A meta-analysis was used to identify the relationship between depression and chronic diseases. Functional Magnetic Resonance Imaging (fMRI) brain scans and common biochemical indexes were compared between the patients and healthy controls. We used behavioural tests, electrophysiology, and molecular profiling techniques to investigate the functional role and molecular basis in mouse models. FINDINGS: After performing a meta-analysis, we targeted the relevance between chronic kidney disease (CKD) and depression. In a CKD mouse model and a patient cohort, depression was induced by impairing the medial prefrontal cortex. The enlarged cohort suggested that urea was responsible for depression. In mice, urea was sufficient to induce depression, interrupt long-term potentiation (LTP) and cause loss of synapses in several models. The mTORC1-S6K pathway inhibition was necessary for the effect of urea. Lastly, we identified that the hydrolysate of urea, cyanate, was also involved in this pathophysiology. INTERPRETATION: These data indicate that urea accumulation in brain is an independent factor causing depression, bypassing the psychosocial stress. Urea or cyanate carbamylates mTOR to inhibit the mTORC1-S6K dependent dendritic protein synthesis, inducing impairment of synaptic plasticity in mPFC and depression-like behaviour. CKD patients may be able to attenuate depression only by strict management of blood urea.


Assuntos
Depressão/etiologia , Depressão/metabolismo , Potenciação de Longa Duração , Carbamilação de Proteínas , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Ureia/sangue , Adulto , Idoso , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Depressão/diagnóstico , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo
17.
Onco Targets Ther ; 12: 7699-7711, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571921

RESUMO

Purpose: Exosomes are key mediators of cellular communication by transporting molecules, including long noncoding RNAs (lncRNAs), and have been regarded as promising non-invasive biomarkers. This study aimed to evaluate the expression pattern and clinical significance of serum exosomal lncRNA antisense hypoxia inducible factor (aHIF) in epithelial ovarian cancer (EOC). Patients and methods: Sixty-two EOC patients in Obstetrics and Gynecology Hospital of Fudan University were enrolled. The expression levels of aHIF in tissues and serum exosomes were examined by RT-qPCR. The origin of serum exosomal aHIF was explored in vitro and in vivo. Univariate and multivariate Cox regression analyses were used to evaluate the prognostic factors of EOC. A prognostic predictive nomogram was formulated in R software. Results: We isolated exosomes, identified exosomal aHIF in the serum of EOC patients. The expression of serum exosomal aHIF was higher in EOC patients and was correlated with the aHIF level in EOC tissues. In vitro and in vivo, the results indicated that serum exosomal aHIF was derived from tumor cells. Kaplan-Meier survival analysis demonstrated that EOC patients with higher serum exosomal aHIF expression had poorer overall survival. Cox multivariate regression model revealed that FIGO stage, residual tumor size, and serum exosomal aHIF level were independent prognostic factors of EOC. Based on the prognostic value of serum exosomal aHIF, we established a nomogram model that showed a good predictive ability for EOC patients. Conclusion: Serum exosomal aHIF is overexpressed in EOC and can serve as a noninvasive predictive biomarker for unfavorable prognosis.

18.
Onco Targets Ther ; 12: 6145-6156, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31496722

RESUMO

Purpose: The long noncoding RNA LINC00673 has emerged as an important regulator of cancer development and progression. However, the clinical significance and biological roles of LINC00673 in epithelial ovarian cancer (EOC) remain unclear. In this study, we aimed to explore the oncogenic roles and underlying molecular mechanisms of LINC00673 in EOC. Patients and methods: The expression levels of LINC00673 in EOC tissues and cell lines were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Real-time cellular analysis (RTCA), flow cytometry, and transwell assays were conducted to investigate cell proliferation, apoptosis, migration and invasion in vitro. Subcutaneous transplanted tumors were established to explore the oncogenic role of LINC00673 in vivo. Differentially expressed genes were analyzed using transcriptome sequencing. Protein levels were determined by Western blot assays. Results: LINC00673 was upregulated in EOC tissues and cell lines compared to their corresponding normal controls. High expression of LINC00673 was associated with advanced International Federation of Gynecology and Obstetrics (FIGO) stage, serous histological subtype, lymph node metastasis and poor prognosis in patients with EOC. LINC00673 was also identified as an independent prognostic factor for EOC. In addition, LINC00673 promoted cell migration, invasion and proliferation and inhibited cell apoptosis in vitro and induced tumor growth in vivo. Mechanistically, opioid growth factor receptor (OGFR) was found to be a potential downstream target gene that mediated the oncogenic effect of LINC00673 in EOC. Conclusion: LINC00673 contributes to EOC proliferation and metastasis and may be a promising prognostic biomarker for EOC patients.

19.
ACS Med Chem Lett ; 10(8): 1180-1186, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31413803

RESUMO

Aberration in FGFR4 signaling drives carcinogenesis and progression in a subset of hepatocellular carcinoma (HCC) patients, thereby making FGFR4 an attractive molecular target for this disease. Selective FGFR4 inhibition can be achieved through covalently targeting a poorly conserved cysteine residue in the FGFR4 kinase domain. We report mass spectrometry assays and cocrystal structures of FGFR4 in covalent complex with the clinical candidate BLU554 and with a series of four structurally related inhibitors that define the inherent reactivity and selectivity profile of these molecules. We further reveal the structure of FGFR1 with one of our inhibitors and show that off-target covalent binding can occur through an alternative conformation that supports targeting of a cysteine conserved in all members of the FGFR family. Collectively, we propose that rotational freedom, steric hindrance, and protein dynamics explain the exceptional selectivity profile of BLU554 for targeting FGFR4.

20.
Environ Pollut ; 254(Pt A): 112938, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31404731

RESUMO

In the present study, the competitive adsorption of Cu2+, Pb2+, and Cd2+ by a novel natural adsorbent (i.e., argillaceous limestone) modified with chitosan (C-AL) was investigated. The results demonstrated that both intraparticle diffusion and chemisorption marked significant contributions to the Cu2+ adsorption process by both raw argillaceous limestone (R-AL) and C-AL in mono-metal adsorption systems. Antagonism was found to be the predominant competitive effect for Cu2+, Pb2+ and Cd2+ adsorptions by C-AL in the multi-metal adsorption system. The three-dimensional simulation and FTIR analysis revealed that the presence of Cu2+ suppressed Pb2+ and Cd2+ adsorptions, while the effect of Cd2+ on Cu2+ and Pb2+ adsorptions was insignificant. The spectroscopic analyses evidenced that amide groups in C-AL played a crucial role in metal adsorption. The preferential adsorptions of Pb2+ > Cu2+ > Cd2+ were likely due to the different affinities of the metals to the lone pair of electrons on the N atom from the amide groups and/or the O atoms from the -OH and -COO- groups on C-AL. The interactions between C-AL and metal ions and between various metal species influenced their competitive adsorption behaviors. C-AL exhibited a superior metal adsorption capacity in comparison with that the capacities of other natural adsorbents reported during the last decade, suggesting its potential practical applications.


Assuntos
Cádmio/química , Carbonato de Cálcio/química , Quitosana/química , Cobre/química , Recuperação e Remediação Ambiental/métodos , Chumbo/química , Adsorção , Íons , Metais Pesados/química , Análise Espectral
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