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1.
J Mater Chem B ; 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32373848

RESUMO

Researchers developing implantable neural probes face a dilemma. Rigid neural probes facilitate direct implantation, but the brain tissue suffers from a vulnerable interface and a strong neuroinflammatory response due to mechanical mismatch between the probe and the brain tissue. Flexible neural probes offer stable interfaces and eliminate neuroinflammatory responses but require auxiliary implantation. Here, we have created a new kind of micro fiber-shaped neural probe with alterable elastic moduli before and after implantation. Carbon nanotube fibers and calcium crosslinked sodium alginate functioned as the core electrode and sheath layer, respectively. The response of calcium crosslinked sodium alginate to water will alter the probe elastic moduli from ∼10 GPa to ∼10 kPa post implantation, which is close to the elastic modulus of brain tissue. The micro fiber probes were directly implanted into mouse brains without any additional materials. After implantation, they became soft and offered dynamically adaptable interfaces with a reduced inflammatory response, benefiting long-term monitoring of neuron signals. Continuous four week monitoring of neuron signals was achieved. The simplicity of the strategy makes it suitable for versatile neuron techniques in neuron recording and modulation.

2.
Scand J Immunol ; 91(6): e12885, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32248557

RESUMO

Autosomal dominant hyper IgE syndrome (AD-HIES) caused by STAT3 gene mutation is a rare primary immunodeficiency disease. To better understand the disease, we described the clinical characteristics of 20 AD-HIES patients in Chongqing, China and explored the effect of mutations in different domains of STAT3 gene on the function of STAT3 protein by Western blot and confocal microscopy. The mean age at onset was 0.12 years. The mean age at diagnosis was 5.31 years. The most common presentation was eczema, pneumonia, skin abscesses and chronic mucocutaneous candidiasis. Seven patients suffered from BCG complications. R382W/Q were identified in 12 patients, V637M mutation in three patients. Three patients have died. The phosphorylated STAT3 was expressed more in wild-type(WT) and R382W mutant STAT3 in the cytoplasm of COS7 cells with epidermal growth factor(EGF) stimulation, less in the V637M mutation and T620S mutation. Dynamic observation showed that STAT3 cytoplasmic accumulation and nuclear translocation occurred rapidly after EGF stimulation in WT-STAT3-GFP, the time of accumulation and nuclear translocation was later and the expression was less in R382W-STAT3-GFP compared with WT-STAT3-GFP, followed by V637M and T620S mutation. These results suggested that our patients had earlier onset, diagnostic age and higher rate of BCG complications. However, our patients had higher incidence of mortality though the earlier diagnostic age. We did not find a significant genotype/phenotype correlation, but Src homology 2 domain mutations (V637M and T620S) had a greater effect on STAT3 phosphorylation and nuclear translocation than DNA-binding domain mutation (R382W) in vitro.

3.
Int J Antimicrob Agents ; : 105950, 2020 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-32234465

RESUMO

Viral respiratory diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) always pose a severe threat to people. First identified in late December 2019, a novel coronavirus (2019-nCoV; SARS-CoV-2) has affected many provinces in China and multiple countries worldwide. The viral outbreak has aroused panic and a public-health emergency around the world, and the number of infections continues to rise. However, the causes and consequences of the pneumonia remain unknown. To effectively implement epidemic prevention, early identification and diagnosis are critical to disease control. Here we scrutinise a series of available studies by global scientists on the clinical manifestations, detection methods and treatment options for the disease caused by SARS-CoV-2, named coronavirus disease 2019 (COVID-19), and also propose potential strategies for preventing the infection.

4.
Toxicol In Vitro ; 66: 104834, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32200033

RESUMO

Cadmium (Cd) is a pervasive harmful metal in the environment. It is a well-known inducer of tumorigenesis, but its mechanism is still unclear. We have previously reported that Cd-induced autophagy was apoptosis-dependent and prevents apoptotic cell death to ensure the growth of A549 cells. In this study, the mechanism was further investigated. Cd treatment increased glucose uptake and lactate release significantly. Meanwhile, the protein level of GLUT1,HKII,PKM2 and LDHA increased in a time-dependent manner, indicating that Cd induced aerobic glycolysis in A549 and HELF cells. The inhibitors of autophagy, 3MA, and CQ, repressed Cd-induced glycolysis-related proteins, indicating that autophagy was involved in Cd-induced glycolysis in A549 and HELF cells. Knockdown of ATG4B or ATG5 by siATG4B and siATG5 decreased Cd-induced glycolysis, while overexpression of ATG4B enhanced glycolysis. These results demonstrated that Cd-induced glycolysis was autophagy-dependent. Then, glycolysis inhibitor, 2DG and siPKM2 could inhibit Cd-induced cell viability and cell cycle progression compared to only Cd treatment, indicating that glycolysis played an important role in Cd-induced cell growth. Finally, co-treatment of transfection of ATG4B-DNA plasmids with 2DG or siPKM2 further demonstrated that the autophagy-glycolysis axis played an important role in Cd-induced cell cycle progression. Taken together, our results suggested that Cd-induced glycolysis is autophagy-dependent and the autophagy-glycolysis axis underlies the mechanism of Cd-induced cell growth in A549 and HELF cells.

5.
Theranostics ; 10(8): 3767-3778, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32206121

RESUMO

Purpose: Lung cancer is the leading cause of cancer related deaths worldwide. We have previously identified many differentially expressed genes (DEGs) from large scale pan-cancer dataset using the Cross-Value Association Analysis (CVAA) method. Here we focus on Progestin and AdipoQ Receptor 4 (PAQR4), a member of the progestin and adipoQ receptor (PAQR) family localized in the Golgi apparatus, to determine their clinical role and mechanism in the development of non-small cell lung cancer (NSCLC). Methods: The protein expression profile of PAQR4 was examined by IHC using tissue microarrays, and the effects of PAQR4 on cell proliferation, colony formation and xenograft tumor formation were tested in NSCLC cells. Real-time RT-PCR, co-immunoprecipitation (co-IP) and GST-pulldown assays were used to explore the mechanism of action of PAQR4. Results: We provided evidence showing that PAQR4 is increased in NSCLC cancer cell lines (A549, H1299, H1650, H1975, H358, GLC-82 and SPC-A1), and identified many mutations in PAQR4 in non-small cell lung cancer (NSCLC) tissues. We demonstrated that PAQR4 high expression correlates with a worse clinical outcome, and that its knockdown suppresses cell proliferation by inducing apoptosis. Importantly, overexpressed PAQR4 physically interacts with Nrf2 in NSCLC cells, blocking the interaction between Nrf2 and Keap1. Conclusion: Our results suggest that PAQR4 depletion enhances the sensitivity of cancerous cell to chemotherapy both in vitro and xenograft tumor formation in vivo, by promoting Nrf2 protein degradation through a Keap1-mediated ubiquitination process.

6.
J Control Release ; 321: 483-496, 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32061623

RESUMO

Chelating Cu from tumors has been verified as an effective and promising strategy for cancer therapy through antiangiogenesis. However, systematic removal Cu by injecting with Cu chelators will result unavoidable side effects, since Cu is indispensable to the body. In this work, a micelle targeting to tumors' newborn vessels based on a polypeptide was developed to co-load DOX and Probe X, which can go through an "OFF-to-ON" procedure to report the Cu+-capture events in vivo in a real-time way by giving near infrared (NIR) fluorescence and photoacoustic signal. By co-delivering antiangiogenesis and chemotherapeutic reagents, the tumor can be significantly suppressed, meanwhile with a low systematic toxicity. Hopefully, this work can offer new insights in designing sophisticated antitumor strategy.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32048425

RESUMO

To date, assessment tools for older people are different between hospitals and nursing homes in China. The difference between assessment tools can lead to poor communication of information between hospitals and nursing homes, which causes discontinuity of care and adverse outcomes when older people are transferred between these different settings. Continuity Assessment Record and Evaluation (CARE) is a comprehensive geriatric assessment tool developed in the United States of America. This study aimed to evaluate the reliability and validity of the Mandarin Version of CARE for older people who are transferred between hospitals and nursing homes. Using a convenience sampling method, 120 older people in hospitals and 120 older people in nursing homes in Shanghai were selected to test the internal consistency, interrater reliability and criterion-related validity of CARE from May to November 2017. When used among hospital, 70.0% (7/10) of the subscales had a Cronbach's alpha coefficients of greater than 0.7, 94.3% (50/53) of the items had an intraclass correlation coefficient (ICC) of greater than 0.75. When used in nursing homes, 90.0% (9/10) of the subscales had a Cronbach's alpha coefficients of greater than 0.7, 94.3% (50/53) of the items had an ICC of greater than 0.75. For both settings, the correlation coefficients of the subscales with their corresponding instruments for criterion-related validity were all greater than 0.8 (p < .01). The Mandarin version of CARE exhibits good reliability and validity. It can be used as an assessment tool for transition between hospitals and nursing homes.

8.
J Med Genet ; 57(6): 371-379, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31888956

RESUMO

BACKGROUND: Congenital vertebral malformations (CVMs) manifest with abnormal vertebral morphology. Genetic factors have been implicated in CVM pathogenesis, but the underlying pathogenic mechanisms remain unclear in most subjects. We previously reported that the human 16p11.2 BP4-BP5 deletion and its associated TBX6 dosage reduction caused CVMs. We aim to investigate the reciprocal 16p11.2 BP4-BP5 duplication and its potential genetic contributions to CVMs. METHODS AND RESULTS: Patients who were found to carry the 16p11.2 BP4-BP5 duplication by chromosomal microarray analysis were retrospectively analysed for their vertebral phenotypes. The spinal assessments in seven duplication carriers showed that four (57%) presented characteristics of CVMs, supporting the contention that increased TBX6 dosage could induce CVMs. For further in vivo functional investigation in a model organism, we conducted genome editing of the upstream regulatory region of mouse Tbx6 using CRISPR-Cas9 and obtained three mouse mutant alleles (Tbx6up1 to Tbx6up3 ) with elevated expression levels of Tbx6. Luciferase reporter assays showed that the Tbx6up3 allele presented with the 160% expression level of that observed in the reference (+) allele. Therefore, the homozygous Tbx6up3/up3 mice could functionally mimic the TBX6 dosage of heterozygous carriers of 16p11.2 BP4-BP5 duplication (approximately 150%, ie, 3/2 gene dosage of the normal level). Remarkably, 60% of the Tbx6up3/up3 mice manifested with CVMs. Consistent with our observations in humans, the CVMs induced by increased Tbx6 dosage in mice mainly affected the cervical vertebrae. CONCLUSION: Our findings in humans and mice consistently support that an increased TBX6 dosage contributes to the risk of developing cervical CVMs.

9.
Bioconjug Chem ; 31(2): 332-339, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-31613602

RESUMO

Over the past two decades, amorphous nanoscale coordination polymers (NCPs) and crystalline nanoscale metal-organic frameworks (NMOFs) have emerged as attractive nanomaterials in biomedical applications, especially in drug delivery, biomedical imaging, and biosensing. The biodegradability, tunable composition, and feasible functionality of NCPs/NMOFs make them excellent contrast agents or nanocarriers for biomedical imaging, including magnetic resonance (MR) imaging, positron emission tomography (PET), computed tomography (CT), optical imaging, and photoacoustic (PA) imaging. In this Topical Review, we will summarize the recent advances of NCPs/NMOFs in biomedical imaging with emphasis on research over the past three years. A variety of imaging technologies based on NCPs/NMOFs will be discussed, followed by the introduction of the application of NCPs/NMOFs in multimodal imaging where optical/MR imaging is highlighted. In the final part, we will make concluding remarks and point out the challenges and prospects for the further development in this area of research.

10.
Toxicol Lett ; 320: 95-102, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31760062

RESUMO

Exposure to organic solvent in industry, including n-hexane is correlated with central-peripheral axonopathy, which is mediated by its active metabolite, 2,5-hexanedione (HD). However, the underlying mechanism is still largely unknown. Recently identified microRNAs (miRNAs) may play important roles in toxicant exposure and in the process of toxicant-induced neuropathys. To examine the role of miRNAs in HD-induced toxicity, neuropathic animal model was successfully built. miRNA microarray analysis revealed 105 differentially expressed miRNAs after HD exposure. Bioinformatics analysis showed that "Axon" and "Neurotrophin Signaling Pathway" was the top significant GO term and pathway, respectively. 7 miRNAs both related to "Axon" and "Neurotrophin Signaling Pathway" were screened out and further confirmed by Real-Time PCR. Correspondingly, the deregulation expression levels of proteins of four target genes (GSK3ß, Map3k1, BDNF and MAP1B) were further confirmed via western blot, verifying the results of gene target analysis. Taken together, our results showed that the axon-related miRNAs to be associated with MAP1B or neurotrophin signal pathways changed in nerve tissues following HD exposure. These miRNAs may play important roles in HD-induced neurotoxicity.


Assuntos
Axônios/efeitos dos fármacos , Hexanonas/toxicidade , MicroRNAs/metabolismo , Síndromes Neurotóxicas/etiologia , Nervo Isquiático/efeitos dos fármacos , Solventes/toxicidade , Medula Espinal/efeitos dos fármacos , Animais , Axônios/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Bases de Dados Genéticas , Regulação da Expressão Gênica , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , MAP Quinase Quinase Quinase 1/genética , MAP Quinase Quinase Quinase 1/metabolismo , Masculino , MicroRNAs/genética , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Síndromes Neurotóxicas/genética , Síndromes Neurotóxicas/metabolismo , Ratos Sprague-Dawley , Nervo Isquiático/metabolismo , Transdução de Sinais , Medula Espinal/metabolismo , Transcriptoma
11.
J Perianesth Nurs ; 35(1): 60-66, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31522954

RESUMO

PURPOSE: Medical staff shortages remain a serious challenge, particularly to medical administrators. We aimed to analyze the effectiveness of a collaborative nursing care model in treatment of diabetic foot. DESIGN: A quasi-experimental pilot study. METHODS: Twenty-eight patients with diabetic foot treated by transverse tibial bone transport between January 2017 and March 2018 were randomized. The observational group received collaborative nursing care, while the control group received usual nursing care. Postoperative dorsal foot skin temperature, visual analog scale, self-rating anxiety scale (SAS) score, and other endpoints were assessed. FINDINGS: Postoperative dorsal foot skin temperature was significantly higher in the observation group than in the control group. Visual analog scale and SAS scores were significantly lower in the observational group than in the control group. CONCLUSIONS: The collaborative nursing care model enhanced collaboration between patient and health care providers, shortened hospital stay, and relieved postoperative pain and anxiety.

12.
J Hazard Mater ; 384: 121390, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31735470

RESUMO

Chronic arsenic exposure is a significantly risk factor for pancreatic dysfunction and type 2 diabetes (T2D). Ferroptosis is a newly identified iron-dependent form of oxidative cell death that relies on lipid peroxidation. Previous data have indicated that ferroptosis is involved in various diseases, including cancers, neurodegenerative diseases, and T2D. However, the concrete effect and mechanism of ferroptosis on pancreatic dysfunction triggered by arsenic remains unknown. In this study, we verified that ferroptosis occurred in animal models of arsenic-induced pancreatic dysfunction through assessing proferroptotic markers and morphological changes in mitochondria. In vitro, arsenic caused execution of ferroptosis in a dose-dependent manner, which could be significantly reduced by ferrostatin-1. Additionally, arsenic damaged mitochondria manifested as diminishing of mitochondrial membrane potential, reduced cytochrome c level and production of mitochondrial reactive oxygen species (MtROS) in MIN6 cells. Using the Mito-TEMPO, we found the autophagy level and subsequent ferroptotic cell death induced by arsenic were both alleviated. With autophagy inhibitor chloroquine, we further revealed that ferritin regulated ferroptosis through the MtROS-autophagy pathway. Collectively, NaAsO2-induced ferroptotic cell death is relied on the MtROS-dependent autophagy by regulating the iron homeostasis. Ferroptosis is involved in pancreatic dysfunction triggered by arsenic, and arsenic-induced ferroptosis involves MtROS, autophagy, ferritin.

13.
Psychiatry Res ; 285: 112731, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31839419

RESUMO

Accumulating evidence has shown that insulin-like growth factors (IGFs) are implicated in schizophrenia. Altered serum levels of IGF-1 have been found in schizophrenia patients and are associated with psychopathological symptoms. However, whether there is a relationship between IGF-1 and cognitive impairment in schizophrenia remains unknown. Thirty schizophrenia patients and 26 healthy controls were recruited for this study. The Positive and Negative Syndrome Scale was adopted to assess schizophrenic symptoms, and a battery of neuropsychological tests was employed to evaluate cognitive function. Serum IGF-1 content was determined by enzyme-linked immunosorbent assay (ELISA). We found that patients with schizophrenia performed more poorly than healthy controls in most cognitive tasks, excluding visual memory. The serum IGF-1 concentrations in schizophrenia patients were much lower than those in controls. Correlation analyses revealed that the levels of serum IGF-1 were positively correlated with executive function and attention scores in patients. Furthermore, IGF-1 was an independent contributor to deficits in executive function and attention among schizophrenia patients. Collectively, serum IGF-1 levels were significantly correlated with cognitive performance in schizophrenia patients, indicating that decreased IGF-1 levels might contribute to the pathophysiology of schizophrenia-associated cognitive impairments. The regulation of IGF-1 signaling might be a potential treatment strategy for cognitive impairments in schizophrenia.

14.
Chemosphere ; 242: 124959, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31669990

RESUMO

Long-term exposure to arsenic can cause liver injury and fibrosis. The activation of hepatic stellate cells (HSCs) plays an essential role in the process of liver fibrosis. We found that NaAsO2 caused liver damage and fibrosis in vivo, accompanied by excessive collagen deposition and HSCs activation. In addition, NaAsO2 upregulated autophagy flux, elevated the level of cytoplasmic cathepsin B (CTSB), and activated the NOD-like receptors containing pyrin domain 3 (NLRP3) inflammasome in a subtle way. Consistent with these findings in vivo, we demonstrated that NaAsO2-induced activation of HSCs depended on CTSB-mediated NLRP3 inflammasome activation in HSC-t6 cells and rats primary HSCs. Moreover, inhibition of autophagy decreased the cytoplasmic CTSB and alleviated the activation of the NLRP3 inflammasome, thereby attenuating the NaAsO2-induced HSCs activation. In summary, these results indicated that NaAsO2 induced HSCs activation via autophagic-CTSB-NLRP3 inflammasome pathway. These findings may provide a novel insight into the potential mechanism of NaAsO2-induced liver fibrosis.


Assuntos
Arsênico/toxicidade , Autofagia , Catepsina B/metabolismo , Células Estreladas do Fígado/metabolismo , Inflamassomos/fisiologia , Cirrose Hepática/induzido quimicamente , Animais , Arsênico/metabolismo , Inflamassomos/metabolismo , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/patologia , Masculino , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos
15.
ACS Appl Mater Interfaces ; 12(1): 373-379, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31840494

RESUMO

A simple and label-free sensing platform with low background based on the chain-displacement triggered self-assembly of Ag NCs was developed for ratiometric visual analysis of intracellular miRNA-21. Based on this sensitively ratiometric sensing approach, a picomole limit detection for miRNA-21 can be obtained. Most importantly, compared with the traditional single base mismatch detection method, our proposed method can realize single base mismatch detection according to the remarkable fluorescence color conversion, rather than simple fluorescence intensity change, which can obviously improve the accuracy and reliability. In addition, successful multicolor real-time monitoring of intracellular miRNA-21 makes the probe a potential candidate for miRNA-21 inhibiting drug screening. Furthermore, MCF-7, HeLa, and normal L02 cells can also be visually differentiated according to the fluorescence color by using the label-free sensing platform, showing its potential prospect in target visual analysis.

16.
J Transl Med ; 17(1): 422, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31847906

RESUMO

BACKGROUND: The growth differentiation factor 11 (GDF11) was shown to reverse age-related hypertrophy on cardiomyocytes and considered as anti-aging rejuvenation factor. The role of GDF11 in regulating metabolic homeostasis is unclear. In this study, we investigated the functions of GDF11 in regulating metabolic homeostasis and energy balance. METHODS: Using a hydrodynamic injection approach, plasmids carrying a mouse Gdf11 gene were delivered into mice and generated the sustained Gdf11 expression in the liver and its protein level in the blood. High fat diet (HFD)-induced obesity was employed to examine the impacts of Gdf11 gene transfer on HFD-induced adiposity, hyperglycemia, insulin resistance, and hepatic lipid accumulation. The impacts of GDF11 on metabolic homeostasis of obese and diabetic mice were examined using HFD-induced obese and STZ-induced diabetic models. RESULTS: Gdf11 gene transfer alleviates HFD-induced obesity, hyperglycemia, insulin resistance, and fatty liver development. In obese and STZ-induced diabetic mice, Gdf11 gene transfer restores glucose metabolism and improves insulin resistance. Mechanism study reveals that Gdf11 gene transfer increases the energy expenditure of mice, upregulates the expression of genes responsible for thermoregulation in brown adipose tissue, downregulates the expression of inflammatory genes in white adipose tissue and those involved in hepatic lipid and glucose metabolism. Overexpression of GDF11 also activates TGF-ß/Smad2, PI3K/AKT/FoxO1, and AMPK signaling pathways in white adipose tissue. CONCLUSIONS: These results demonstrate that GDF11 plays an important role in regulating metabolic homeostasis and energy balance and could be a target for pharmacological intervention to treat metabolic disease.

17.
Int J Med Mushrooms ; 21(6): 583-593, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679230

RESUMO

Tacrine is the first drug licensed for the treatment of Alzheimer disease. Unfortunately, reversible hepatotoxicity limits its clinical use. In our previous study, we found that tacrine induced apoptosis in HepG2 cells by reactive oxygen species (ROS) formation and mitochondria dysfunction. Inonotus obliquus is a mushroom traditionally used as a folk medicine in Asia. In this study, the possible protective effect of polysaccharides from I. obliquus was investigated. The results showed that I. obliquus polysaccharides (IOP) reduced tacrine-induced apoptosis in HepG2 cells. Inhibition of tacrine-induced ROS generation, 8-OHdG formation in mitochondrial DNA, and loss of the mitochondrial transmembrane potential by IOP were also observed. Furthermore, IOP decreased the cytochrome c release and activation of caspase-3 induced by tacrine. These data suggest that IOP could inhibit tacrine-induced apoptosis in HepG2 cells. The protection is mediated by an antioxidant protective mechanism. Consumption of IOP may be a plausible way to prevent tacrine-induced hepatotoxicity.


Assuntos
Apoptose/efeitos dos fármacos , Basidiomycota/química , Polissacarídeos Fúngicos/farmacologia , Mitocôndrias/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Tacrina/farmacologia , Ásia , Células Hep G2 , Humanos , Medicina Tradicional , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/fisiologia , Espécies Reativas de Oxigênio/antagonistas & inibidores
18.
J Cancer ; 10(23): 5843-5851, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737120

RESUMO

Background: The incidence and mortality rate of gastric cancer has markedly declined over the past few decades, due to the progress and advances in the development of diagnostic and treatment regimens. However, there is still a large portion of patients who are first diagnosed during the advanced stage of gastric cancer when chemotherapy is needed. Unfortunately, resistance to chemotherapeutic agents is the most frequent occurrence during treatment, which indicates a need for the discovery of novel therapeutic anticancer drugs. Methods: The tumor-suppression effect of eight different cucurbitacins was evaluated in gastric cancer cell lines, and the Cucurbitacin E (CuE) showing the greatest effect was used in further studies to explore the mechanism and potential synergistic effect of Dox both in vitro and in vivo. Results: Compared with other cucurbitacins, CuE showed the greatest antiproliferative activity against the gastric cancer cell lines. Further investigations revealed that CuE suppressed the growth of gastric cancer cell lines through the induction of G2/M arrest and subsequent apoptosis by impairing AKt activation and reducing its expression in gastric cancer cells. Furthermore, our results indicate that CuE can significantly enhance the cytotoxicity of doxorubicin (Dox) both in vitro and in vivo. Conclusion: In summary, we present the first evidence of the efficacy of CuE for the inhibition of gastric cancer growth and the synergistic antitumorigenic effect of CuE and Dox, both in vitro and in vivo.

19.
Cardiovasc Res ; 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31591643

RESUMO

AIMS: Sinus venous valve (SVV) and sinoatrial node (SAN) develop together at the sinoatrial junction during embryogenesis. SVV ensures unidirectional cardiac input and SAN generates sinus rhythmic contraction, respectively; both functions are essential for embryonic survival. We aim to reveal the potential role of endocardial NOTCH signaling in SVV and SAN formation. METHODS AND RESULTS: We specifically deleted Notch1 in the endocardium using an Nfatc1Cre line. This deletion resulted in underdeveloped SVV and SAN, associated with reduced expression of T-box transcription factors, Tbx5 andTbx18, which are essential for the formation of SVV and SAN. The deletion also led to decreased expression of Wnt2 in myocardium of SVV and SAN. WNT2 treatment was able to rescue the growth defect of SVV and SAN resulted from the Notch1 deletion in whole embryo cultures. Furthermore, the Notch1 deletion reduced the expression of Nrg1 in the SVV myocardium and supplement of NRG1 restored the growth of SVV in cultured Notch1 knockout embryos. CONCLUSION: Our findings support that endocardial NOTCH1 controls the development of SVV and SAN by coordinating myocardial WNT and NRG1 signaling functions.

20.
Toxicology ; 428: 152304, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31586597

RESUMO

Zearalenone (ZEA), one of the mycotoxins widely found in food and feed, can stimulate an inflammatory reaction. In the present study, we demonstrated that ZEA induced the activation of NLRP3 inflammasome even pyroptotic cell death in rat Insulinoma Cell Line (INS-1). Meanwhile, according to the results of western blot and TEM, the level of autophagy was elevated by ZEA, which protected against the activation of NLRP3 inflammasome and inflammatory response caused by ZEA. Furthermore, we indicated that ZEA-induced NF-κB p65 activation contributed to the activation of the NLRP3 inflammasome, inflammatory response, and pyroptosis in INS-1 cells, which were indicated by western blot and immunofluorescence, and the activation of NF-κB p65 induced by ZEA was autophagy-dependent. This study demonstrates that ZEA induces NLRP3-dependent pyroptosis via activation of NF-κB modulated by autophagy in INS-1 cells.

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