Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.411
Filtrar
1.
Immunol Cell Biol ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919905

RESUMO

Epicutaneous sensitization (EC) with protein allergens is the most important sensitization route for atopic dermatitis. Plasmacytoid dendritic cells (PDCs) are characterized by massive secretion of IFN-α. B6 mice are Th1-prone and are representative of human non-atopy, whereas BALB/c mice are Th2-prone and are representative of human atopy. Here, we show that naive BALB/c mice contain a greater number of non-activated plasmacytoid dendritic cells in peripheral lymph nodes (LNs) than do naive B6 mice. Naïve BALB/c mice also have more CD8α- subset in lymph nodes than naïve B6 mice. Moreover, in vivo depletion of plasmacytoid dendritic cells during epicutaneous sensitization results in enhanced Th2 responses in BALB/c mice, but not in B6 mice. Mechanistically, when BALB/c mice undergo epicutaneous sensitization there is an increase in plasmacytoid dendritic cells entering draining lymph nodes. These cells exhibit modest activation including comparable co-stimulator expression but increased cytokine expression compared with those of naive mice. In vivo depletion of plasmacytoid dendritic cells during epicutaneous sensitization significantly increases the activation of dermal dendritic cells suggesting a regulatory effect on these cells. To this end, a suppressive effect of plasmacytoid dendritic cells on conventional dendritic cells was also demonstrated in vitro. Further, in vivo blockade of IFN-α by an anti-IFNAR Ab or in vivo reduction of IFN-α production of plasmacytoid dendritic cells by anti-siglec-H Ab both resulted in enhanced activation of dermal dendritic cells. Collectively, our results demonstrate that plasmacytoid dendritic cells suppress Th2 responses induced by epicutaneous sensitization via IFN-α-mediated regulation of dermal dendritic cells.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31897846

RESUMO

PURPOSE: The present study was intended to identify genetic causes of infertile patients with recurrent failure of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) attempts. METHODS: Infertile patients with recurrent IVF/ICSI failure from Shanghai Ji Ai Genetics & IVF Institute and the Ninth Hospital affiliated with Shanghai Jiao Tong University were recruited. Genomic DNA samples were extracted from their peripheral blood. Whole-exome sequencing and Sanger validation were performed to identify candidate variants. RESULTS: We identified novel transducin-like enhancer of split 6 (TLE6) gene mutations in three patients with recurrent IVF/ICSI failure. One patient carried a homozygous missense mutation (c.1226G>A; p.Arg409Gln) with subsequent fertilization failure, while the other two patients carried either a homozygous missense mutation (c.1621G>A; p.Glu541Lys) or a compound heterozygous missense mutation (c.388G>A/c.1507G>A; p.Asp130Asn/p.Val503Ile) and had viable but low-quality embryos. CONCLUSIONS: Our study expands the mutational and phenotypic spectrum of TLE6 and suggests the important role of TLE6 during embryonic development. Our findings have implications for the genetic diagnosis of female infertility with recurrent IVF/ICSI failure.

3.
Scand J Clin Lab Invest ; : 1-6, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31899967

RESUMO

The most prominent event that defines acute coronary syndrome (ACS) is the formation of an intra-arterial thrombus, usually resulting from activation of platelet and fibrinogen at the ruptured plaque. Usually, conventional coagulation tests (CCTs) are used to estimate the hemostatic properties of patients. However, CCTs have significant limitations because they each assess individual aspects of the coagulation cascade, which is a complex multifaceted process. And CCTs are performed with platelet-poor plasma, while the contribution of platelets to clot formation is not measured. In contrast, thromboelastography (TEG) is a test for global hemostasis with whole blood, from the beginning of coagulation through clot formation to the ending with fibrinolysis. The aim of this study was to investigate whether TEG parameters could be surrogate biomarkers of thrombus formation process and diagnosis of ACS. Receiver operating characteristic(ROC)curve was used to evaluate the diagnosis performance of each index. Logistic regression analysis was utilized to define the independent risk factors of ACS. The results showed that the shear elastic modulus parameter (G) was an independent diagnostic indicator for ACS (odds ratio [OR], 2.600; 95% confidence interval [CI], 2.035-3.322). The area under ROC curve of G was 0.866. The optimal cut-off value for the diagnosis of ACS was 10.55 dyne/cm2, while the sensitivity was 66.2% and the specificity was 92.4%. In conclusion, G could be used as an optimal indicator of activation of platelet and fibrinogen, which is eligible to be a useful biomarker for early diagnosis of ACS.

4.
Theranostics ; 10(1): 36-49, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31903104

RESUMO

Mesenchymal stem cells (MSCs) transplantation is a promising antifibrotic strategy but facing clinical controversies. Inspired by advances in nanomedicine, we aimed to bypass these clinical barriers of MSCs by identifying the key antifibrotic molecule of MSCs and developing a specific liver-targeting nanocarrier. Methods: Cytokines secreted by MSCs were examined with serum stimulation of cirrhotic patients. Immunohistochemistry, microarray, immunoblotting, and quantitative real-time PCR (qRT-PCR) were applied to identify the critical antifibrotic cytokine and to discover its role in modulating antifibrotic effects. Biomineralization method was used to prepare calcium phosphate nanoparticles (NPs). The targeting and therapeutic efficiency of NPs were evaluated by in vivo imaging and biochemical studies on fibrotic mice induced by CCl4. Results: The stimulated MSCs exhibited high-level expression of Tumor necrosis factor (TNF)-stimulated gene 6 (TSG-6). On animal study, exogenous administration of TSG-6 alone can ameliorate liver fibrosis while TSG-6 knocked MSCs (Lv-TSG-6 MSCs) lost antifibrotic effects. Further studies verified the importance of TSG-6 and identified its antifibrotic mechanism by modulating M2 macrophages and increasing matrix metalloproteinase 12 (MMP12) expression. Additionally, we found a feedback loop between TSG-6, MMP12 and pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß), which may improve our understanding of the aggravating process of cirrhosis and antifibrotic mechanisms of TSG-6 and MSCs. Based on these findings, we developed calcium phosphate nanoparticles (CaP@BSA NPs) by biomineralization method using bovine serum albumin (BSA) as the biotemplate. Imaging tracking and drug loading studies showed specific liver targeting and high TSG-6 loading efficacy of as-prepared CaP@BSA NPs. In vivo therapeutic study further demonstrated the improved therapeutic effects of TSG-6 loaded CaP@BSA. Conclusions: TSG-6 was a major antifibrotic cytokine of MSCs, TSG-6 loaded CaP@BSA NPs showed specific liver accumulation and improved therapeutic effects, which indicated translational potentials of CaP@BSA as a promising drug carrier for the liver disease management.

5.
DNA Cell Biol ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31913706

RESUMO

Hepatocellular carcinoma (HCC), the sixth most common malignancy worldwide, is characterized by a dismal prognosis due to high recurrence and metastasis rates. Thus, the need for the development of novel chemotherapeutic drugs is urgent. Cyclovirobuxine D (CVB-D), a steroidal alkaloid extracted from Buxus microphylla that has been extensively used to relieve the symptoms of cardiovascular diseases, has shown promising antineoplastic effects in recent studies. However, the therapeutic effects and underlying mechanisms of CVB-D on HCC remain largely unelucidated. This study experimentally indicated that CVB-D can repress HCC cell proliferation by arresting the cell cycle in G2 phase and can facilitate apoptosis. In addition, the migratory and invasive capabilities of HCC cells were noticeably attenuated by a nonlethal dose of CVB-D, and this attenuation was correlated with the inhibition of epithelial-mesenchymal transition (EMT). Moreover, in vivo, CVB-D displayed excellent anticancer effects in HCC tumor-bearing nude mice. Regarding the molecular mechanisms of CVB-D activity, decreased Slug expression was determined to be associated with the aforementioned anti-HCC functions of this extract, which might be regulated by epidermal growth factor receptor (EGFR) through the focal adhesion kinase (FAK)-associated PI3K/AKT and MEK/ERK1/2 signaling pathways. Collectively, our results revealed the suppressive effects of CVB-D on progressive behaviors of HCC, including proliferation, migration, invasion, and EMT, in addition to its outstanding proapoptotic effects, which were correlated with the inhibition of the EGFR-FAK-AKT/ERK1/2-Slug signaling pathway. These discoveries provide an experimental and theoretical foundation for the use of CVB-D as a promising candidate for HCC therapy.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31917182

RESUMO

OBJECTIVE: In foam sclerotherapy for varicose veins, ultrasound can track the spread of foam in only one direction. We hypothesized that using fluoroscopy in combination with ultrasound can reveal the spread of foam to deep veins through perforator veins and to other varicose veins in different directions. In this study, we examined the safety and effectiveness of ultrasound- and fluoroscopy-guided foam sclerotherapy for lower extremity venous ulcers. METHODS: This retrospective study included all patients receiving ultrasound- and fluoroscopy-guided foam sclerotherapy for varicose ulcers (Clinical, Etiology, Anatomy, and Pathophysiology class 6) of the lower extremities at the Fourth Affiliated Hospital of Jiangsu University (Zhenjiang, China) between May 1, 2016, and April 30, 2018. Polidocanol foam sclerosant was injected through indwelling needles (placed every 20 cm for saphenous veins and every 5-10 cm for others) into the varicose veins. When the contrast medium in the target vessels was replaced by the hypointense foam sclerosant or on signs of foam entry into the perforator veins under fluoroscopy, the injection was stopped and the site was manually pressed. All patients received postprocedure compression with elastic bandages until ulcer healing and compression stockings (30-40 mm Hg) thereafter. RESULTS: A total of 35 patients (42 limbs) were included. The maximal ulcer diameter was 3.6 ± 1.4 cm (range, 1.1-5.8 cm). The number of injection sites ranged from 3 to 10; total foam amount ranged from 4.5 to 35 mL. All 35 patients completed 12-month follow-up. Ulcer healing rate was 100%, and 1-year recurrence rate was 2.9%. The Venous Clinical Severity Score was 12.98 ± 3.91 before treatment, decreasing to 3.02 ± 2.39 at 12 months (P < .01). Superficial thrombophlebitis developed in 21 (50%) limbs. No deep venous thrombosis or pulmonary embolism was observed during follow-up. Among the 33 limbs (27 patients) with ultrasound examination at 12 months, 28 (84.8%) limbs had complete occlusion and the remaining 5 (15.2%) had recanalization. CONCLUSIONS: Ultrasound- and fluoroscopy-guided foam sclerotherapy is safe and effective for the treatment of venous ulcers of the lower extremities.

7.
Brain Behav ; : e01492, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31909567

RESUMO

OBJECTIVE: Neurologic deterioration (ND) and functional outcome after ischemic stroke (IS) are not accurately predicted by clinical pictures on admission. The aim of present study was to investigate the association of variants in P53 apoptotic pathway genes with ND and functional outcome after IS. METHODS: Genotypes of nine variants in apoptosis-relevant genes were measured in patients with acute IS. Gene-gene interactions were analyzed by generalized multifactor dimensionality reduction (GMDR). The primary outcome was ND. ND was diagnosed in patients who worsened ≥2 points (National Institutes of Health Stroke Scale [NIHSS] score) within the first 10 days of stroke onset. The secondary outcome was functional status at 90 days after IS as measured by modified Rankin Scale (mRS) score. RESULTS: A total of 705 enrolled patients, ND occurred in 174 (24.7%) patients, and 184 (26.1%) patients were poor functional outcome (mRS score > 2). Although the nine variants were not significantly associated with ND and functional outcome by univariate analysis, there was a gene-gene interaction among P53 rs1042522, MDM-2 rs2279744, and MMP-9 rs3918242 using GMDR analysis. The high-risk interaction among the three variants was independently associated with higher risk of ND (HR, 2.04, 95% CI: 1.22-5.64, p = .018) and poor functional outcome (OR, 2.68, 95% CI: 1.68-7.86, p = .004) after adjusting for the covariates. CONCLUSION: The interactions among P53 rs1042522, MDM-2 rs2279744, and MMP-9 rs3918242 may increase the risk of ND and poor functional outcome and may be considered as a genetic marker of predicting ND and poor functional outcome after stroke.

8.
Int J Mol Sci ; 21(2)2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31936264

RESUMO

Magnetic graphene composites (MGCs), which are composed of magnetic nanoparticles with graphene or its derivatives, played an important role in sensors development. Due to the enhanced electronic properties and the synergistic effect of magnetic nanomaterials and graphene, MGCs could be used to realize more efficient sensors such as chemical, biological, and electronic sensors, compared to their single component alone. In this review, we first reviewed the various routes for MGCs preparation. Then, sensors based on MGCs were discussed in different groups, including optical sensors, electrochemical sensors, and others. At the end of the paper, the challenges and opportunities for MGCs in sensors implementation are also discussed.

9.
Immunol Cell Biol ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31943336

RESUMO

Dimethyl itaconate (DI) is a membrane-permeable itaconate derivative with anti-inflammatory functions. However, the anti-inflammatory effect of DI has never been studied in fungal keratitis. In this study, we tested the protective effect of DI against fungal keratitis and assessed the role of NF-E2-related factor-2 (Nrf2)/ heme oxygenase-1 (HO-1) signaling in this process. Eyes of C57BL/6 (B6) mice were treated with 2 mM DI after infection with Aspergillus fumigatus (A. fumigatus). Human corneal epithelial cells (HCECs) were pretreated with 0.25 mM DI and then incubated with A. fumigatus. Clinical scoring, slit-lamp photography, myeloperoxidase (MPO) determination, flow cytometry and immunostaining were used to assess the disease response and treatment efficacy. PCR, Western blot and ELISA were used to assess the expression of IL-1ß, CXCL1, IL-6, IL-8, Nrf2 and HO-1. In addition, quantification of viable fungi, absorbance assays and fluorimetry were used to measure DI fungistatic activity. We observed that DI-treated eyes showed decreased clinical scores, fungal loads, polymorphonuclear neutrophil (PMN) infiltration and cytokine expression, compared with PBS-treated infected eyes. DI treatment decreased the cytokine levels in infected corneas and in HCECs stimulated with A. fumigatus. Moreover, DI treatment increased Nrf2 and HO-1 expression in corneas and nuclear Nrf2 accumulation in HCECs. DI-induced cytokine downregulation was inhibited by pretreatment with an Nrf2 or HO-1 inhibitor. Finally, DI treatment reduced the A. fumigatus absorbance and fungal mass. These data indicate that DI protects against fungal keratitis by limiting inflammation via the Nrf2/HO-1 signaling pathway and that DI inhibits the growth of A. fumigatus.

10.
Chem Rec ; 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31944590

RESUMO

The nano-oxide materials with special structures prepared by template methods have a good dispersion, regular structures and high specific surface areas. Therefore, in some areas, improved properties are observed than conventional bulk oxide materials. For example, in the treatment of dye wastewater, the treatment efficiency of adsorbents and catalytic materials prepared by template method was about 30 % or even higher than that of conventional samples. This review mainly focuses on the progress of inorganic, organic and biological templates in the preparation of micro- and nano- oxide materials with special morphologies, and the roles of the prepared materials as adsorbents and photocatalysts in dye wastewater treatment. The characteristics and advantages of inorganic, organic and biological template are also summarized. In addition, the applications of template method prepared oxides in the field of sensors, drug carrier, energy materials and other fields are briefly discussed with detailed examples.

11.
Eur J Med Chem ; 188: 112026, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31918072

RESUMO

Methicillin-resistant Staphylococcus aureus and the formation of persistent nongrowing subpopulations (persisters) is a serious threat to human. Our previous studies have proved that two cajaninstilbene acid (CSA) analogues, compound 5b and 5j display remarkable antibacterial activities, especially overcoming drug resistance of methicillin-resistant Staphylococcus aureus (MRSA). Present study found that 5b and 5j are capable of eradicating MRSA persisters. However, their underlying antibacterial mechanism is still obscure. In this study, biological evaluation was performed by transmission electron micrograph, membrane permeability and membrane depolarization experiment to reveal the effects of drugs on bacteria. Further, affinity-based protein profiling and transcriptional profiling were performed to characterise the protein targets in bacterial. Biological evaluation suggested that 5b has an effect on bacterial membrane, affinity-based protein profiling identified that 5b targets membrane associated protein PgsA and verified by in vitro labelling profile. Transcriptional profiling indicated that 5b interferes in phosphatidylglycerol (PG) synthesis pathway. This study identified a novel antibacterial target PgsA and it might be a potential target to combat the resistant bacteria.

12.
Pancreas ; 49(1): 96-104, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31856084

RESUMO

OBJECTIVE: Long noncoding RNAs (lncRNAs) have received increasing attention as potential regulators of several biological processes. However, the precise effects of lncRNAs in acute pancreatitis (AP) have seldom been studied. This study aimed to describe the microarray-based differential expression profile of messenger RNA (mRNAs) and lncRNAs in AP and identify candidate biomarkers for the diagnosis, prognosis, and treatment of AP. METHODS: A rat model of AP was generated with retrograde pancreatic ductal injection of sodium taurocholate, and the pancreas was harvested for microarray detection. The biological functions of differentially expressed mRNAs noted from microarray data were assessed by bioinformatics analysis. A coding-noncoding gene coexpression network was built for the most promising mRNAs, from which 10 lncRNAs were selected for subsequent validation by real-time quantitative reverse transcription polymerase chain reaction. RESULTS: There were 1156 lncRNAs and 3022 mRNAs distinctively dysregulated in rats with AP relative to the controls. The significantly enriched Gene Ontology term associated with upregulated mRNAs was immune system process. Kyoto Encyclopedia of Genes and Genomes functional analysis demonstrated that the upregulated transcripts were highly enriched in natural killer cell-mediated cytotoxicity. CONCLUSIONS: Further research is needed to establish lncRNAs uc.308-, BC158811, BC166549, BC166474, and BC161988 as diagnostic and therapeutic targets.

13.
Neoplasia ; 22(1): 1-9, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31751859

RESUMO

Sorafenib is the first approved systemic therapy for advanced hepatocellular carcinoma (HCC) and is the first-line choice in clinic. Sustained activation of receptor tyrosine kinases (RTKs) is associated with low efficacy of sorafenib in HCC. Activation of liver X receptor (LXR) has been reported to inhibit some RTKs. In this study, we found that the LXR agonist enhanced the anti-tumor activity of sorafenib in a subset of HCC cells with high LXR-ß/α gene expression ratio. Mechanically, the activation of LXR suppressed sorafenib dependent recruitment of MET and epidermal growth factor receptor (EGFR) in lipid rafts through cholesterol efflux. Our findings imply that LXR agonist can serve as a potential sensitizer to enhance the anti-tumor effect of sorafenib.

14.
Infect Drug Resist ; 12: 3695-3702, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819551

RESUMO

Background and objective: Infections caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E. coli) have raised public-health concerns and are becoming a global health challenge. This study aimed to investigate changes in antimicrobial resistance of E. coli responsible for early-onset sepsis (EOS) in a perinatal center in eastern China. Methods: Two periods, 2002 to 2008 and 2012 to 2018, were investigated. EOS was defined as the presence of a single potentially pathogenic bacterium grown from blood or cerebrospinal fluid in cultures drawn in any newborn infant within 72 hrs of birth. The changes in antimicrobial resistance of E. coli were analyzed. Results: A total of 163 cases of EOS were identified, and E. coli continued to be the leading pathogen in our neonatal intensive care unit (NICU). Overall resistance of E. coli to third-generation cephalosporins increased from 14.3% in 2002-2008 to 46.7% in 2012-2018 (p<0.05). This resistance pattern closely parallels ESBL production. Compared to that from term infants, E. coli isolated from preterm infants had a significantly higher rate of resistance to ampicillin (93.3% vs 48.4%, p<0.01) and gentamicin (60.0% vs 9.4%, p<0.01), as well as a higher rate of ESBL production (66.7% vs 15.6%, p<0.01). Conclusion: We conclude that ESBL-producing multi-drug resistant E. coli has emerged as the major pathogen responsible for early-onset neonatal sepsis, particularly in preterm infants. Clinicians should consider this trend and attempt to select proper effective antibiotics as the empirical treatment for early-onset neonatal sepsis.

15.
Shanghai Kou Qiang Yi Xue ; 28(4): 384-387, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31792478

RESUMO

PURPOSE: To investigate the effect of pit and fissure sealant combined with fluorine protective paint on prevention of children caries aged 5-8 years old. METHODS: Convenience sampling method was used to select 120 children who received oral health care in the First Affiliated Hospital of Zhejiang University and Hangzhou Dental Hospital from January 2014 to January 2017. They were grouped by random number table method: the control group (60 cases, 109 teeth) underwent pit and fissure sealant, and the experimental group (60 cases, 112 teeth) underwent pit and fissure sealant combined with fluorine protective paint. The patients were followed up for 2 years to compare the incident of dental caries. SPSS20.0 software package was used to analyze the data. RESULTS: The incidence of dental caries in the experiment group (2.68%) was significantly lower than that in the control group (10.09%) (P<0.05).The incidence of adjacent caries in the experiment group (1.79%) was significantly lower than that in the control group (9.17%) (P<0.05). At 1 and 2 years after sealing, the shedding rate(0.00%, 3.33%) of the sealant in the experiment group was significantly lower than that in the control group (10.00%, 15.00%)(P<0.05).The mean caries of the experiment group was significantly lower than that of the control group(P<0.05). CONCLUSIONS: The effect of combined pit and fissure sealant and fluoride protective paint on the prevention of dental caries in children aged 5-8 years old is ideal, which can reduce the incidence of dental caries and adjacent caries, reduce the mean caries, and keep the sealant intact. It is worthy of clinical promotion.

17.
ACS Nano ; 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31833366

RESUMO

Glucose oxidase (GOx) has been recognized as a "star" enzyme catalyst involved in cancer treatment in the past few years. Herein, GOx is mineralized with manganese-doped calcium phosphate (MnCaP) to form spherical nanoparticles (GOx-MnCaP NPs) by an in situ biomimetic mineralization method, followed by the loading of doxorubicin (DOX) to construct a biodegradable, biocompatible, and tumor acidity-responsive nanotheranostics for magnetic resonance imaging (MRI) and cascade reaction-enhanced cooperative cancer treatment. The GOx-driven oxidation reaction can effectively eliminate intratumoral glucose for starvation therapy, and the elevated H2O2 is then converted into highly toxic hydroxyl radicals via a Mn2+-mediated Fenton-like reaction for chemodynamic therapy (CDT). Moreover, the acidity amplification due to the gluconic acid generation will in turn accelerate the degradation of the nanoplatform and promote the Mn2+-H2O2 reaction for enhanced CDT. Meanwhile, the released Mn2+ ions can be used for MRI to monitor the treatment process. After carrying the anticancer drug, the DOX-loaded GOx-MnCaP can integrate starvation therapy, Mn2+-mediated CDT, and DOX-induced chemotherapy together, which showed greatly improved therapeutic efficacy than each monotherapy. Such an orchestrated cooperative cancer therapy demonstrated high-efficiency tumor suppression on 4T1 tumor-bearing mice with minimal side effects. Our findings suggested that the DOX-loaded GOx-MnCaP nanotheranostics with excellent biodegradability and biocompatibility hold clinical translation potential for cancer management.

18.
Life Sci ; : 117165, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31838136

RESUMO

AIMS: Previous work has reported the closely correlation between inflammation and carcinogenesis, while the role of NALP3, the key component of inflammasome activation in NSCLC remains elusive. This study was to unravel the mechanism of NALP3 on modulating NSCLC cancer cell growth. METHODS: IHC and immuno-blot were performed to analyze expression of NALP3 and indicated molecules. CCK-8 and xenograft nude mice assay were used to evaluate cell growth in vitro and in vivo. Bioenergetics assay was performed to measure OXPHOS and aerobic glycolysis. siRNA and shRNA were constructed to knockdown endogenous NALP3 and DNMT1. Co-immunoprecipitation was applied to confirm the interaction between NALP3 and DMAP1. BioProfile FLEX analyzer and Lactate Reagent Kit were used to measure relative level glucose uptake and lactate production. KEY FINDINGS: We reported NALP3 were up-regulated in NSCLC tumor tissues. NALP3 depletion suppressed cancer cell growth in vitro and in vivo. Moreover, data showed depletion of NALP3 promoted cell bioenergetics switch from aerobic glycolysis to OXPHOS. Additionally, we found NALP3 interacted with DMAP1 and alteration of NALP3 increased DNMT1 level. Subsequently, we clarified depletion of DNMT1 significantly suppressed NSCLC cell growth and orchestrated cellular metabolism which was similar to the effects of NALP3 knockdown. Finally, our data showed high NALP3 was associated with poor outcomes, and correlated with TNM stage and differentiation. SIGNIFICANCE: Current study elucidated NALP3 could promote metabolic reprogramming to regulate NSCLC cell growth and suggested that NALP3 may be considered as a novel biomarker and therapeutic target for NSCLC patients.

19.
Inorg Chem ; 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31880926

RESUMO

All-inorganic CsPbX3 (X = Cl, Br, I) perovskite quantum dots (QDs) have great potential for various applications due to their excellent photoluminescence properties. However, poor stability under long-term storage hinders their applications. Herein we report the utilization of porous boron nitride nanofibers (BNNFs) as a promising carrier for anchoring of CsPbBr3 QDs. Due to the good dispersion and immobilization of CsPbBr3 QDs, the resulting CsPbBr3/BNNF composites show excellent photostability and superior long-term storage stability in an air environment. Moreover, the CsPbBr3/BNNF composites exhibit an interesting ammonia-responsive behavior: i.e., a distinct decrease in photoluminescence intensity upon exposure to ammonia gas and the subsequent photoluminescence recovery after post-treatment in nitrogen gas. Even after treatment with ammonia gas for 3 h, the composites can still be recovered under nitrogen gas treatment. The fast response, reversibility, and stability of CsPbBr3/BNNF composites in the presence of ammonia gas could inspire a broader range of applications.

20.
Int J Mol Sci ; 21(1)2019 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-31881805

RESUMO

The anti-tumor activity of diosgenin, a new steroidal constituent present in fenugreek, on two human breast cancer cell lines, MCF-7 and Hs578T, was studied. Diosgenin treatment resulted in cell growth inhibition, cell cycle arrest, and apoptosis in concentration- and time-dependent manners in both cell lines. Western blot analyses of whole cell lysates for cell cycle proteins showed that diosgenin altered phosphorylated cyclin checkpoint1 (p-Chk1Ser345) and cyclin B expression, which resulted in G2/M phase blockade. Mechanistically, Cdc25C-Cdc2 signaling was involved in inactivating Chk1Ser345 by p53-dependence in MCF-7 cells and p21-dependence in Hs578T cells that are p53-deficient. Moreover, diosgenin induced a significant loss of the mitochondrial membrane potential in breast cancer cells, and prominently affected cell death through down-regulation of the anti-apoptotic protein, Bcl-2. This released cytochrome c and activated the caspase signaling cascade. Taken together, these findings reveal that the anti-proliferative activity of diosgenin involves the induction of G2/M phase arrest via modulating the Cdc25C-Cdc2-cyclin B pathway and mitochondria-mediated apoptosis in human breast cancer cell lines. This suggests the potential usefulness of diosgenin in treating breast cancer.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA