Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 43
Filtrar
1.
J Cell Biol ; 223(8)2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38713825

RESUMO

Whether, to what extent, and how the axons in the central nervous system (CNS) can withstand sudden mechanical impacts remain unclear. By using a microfluidic device to apply controlled transverse mechanical stress to axons, we determined the stress levels that most axons can withstand and explored their instant responses at nanoscale resolution. We found mild stress triggers a highly reversible, rapid axon beading response, driven by actomyosin-II-dependent dynamic diameter modulations. This mechanism contributes to hindering the long-range spread of stress-induced Ca2+ elevations into non-stressed neuronal regions. Through pharmacological and molecular manipulations in vitro, we found that actomyosin-II inactivation diminishes the reversible beading process, fostering progressive Ca2+ spreading and thereby increasing acute axonal degeneration in stressed axons. Conversely, upregulating actomyosin-II activity prevents the progression of initial injury, protecting stressed axons from acute degeneration both in vitro and in vivo. Our study unveils the periodic actomyosin-II in axon shafts cortex as a novel protective mechanism, shielding neurons from detrimental effects caused by mechanical stress.


Assuntos
Actomiosina , Axônios , Estresse Mecânico , Animais , Camundongos , Actomiosina/metabolismo , Axônios/metabolismo , Axônios/patologia , Cálcio/metabolismo , Células Cultivadas , Degeneração Neural/patologia , Ratos
2.
Animals (Basel) ; 14(9)2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38731330

RESUMO

The African swine fever virus (ASFV) encodes numerous proteins characterized by complex immune escape mechanisms. At present, the structure and function of these proteins, including the F317L protein, have yet to be fully elucidated. In this study, we examined the immunogenicity of the F317L protein. Mice were subcutaneously immunized with the F317L protein using initial and subsequent booster doses, and, at the 28th day post-treatment, we assessed the humoral and cellular immune responses of mice. The F317L protein stimulated production of specific antibodies and activated humoral immune responses. In addition, F317L stimulated the production of large amounts of IFN-γ by splenic lymphocytes, thereby activating cellular immune responses. Using informatics technology, we predicted and synthesized 29 F317L protein T cell epitopes, which were screened using IFN-γ ELISpot. Among these, the F25 (246SRRSLVNPWT255) peptide was identified as having a stronger stimulatory effect than the full-length protein. Collectively, our findings revealed that the ASFV F317L protein can stimulate both strong humoral and cellular immunity in mice, and that the F25 (246SRRSLVNPWT255) peptide may be a potential active T cell epitope. These findings will provide a reference for further in-depth studies of the F317L protein and screening of antigenic epitopes.

3.
Molecules ; 28(17)2023 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-37687235

RESUMO

As a fast and non-destructive spectroscopic analysis technique, Raman spectroscopy has been widely applied in chemistry. However, noise is usually unavoidable in Raman spectra. Hence, denoising is an important step before Raman spectral analysis. A novel spectral denoising method based on variational mode decomposition (VMD) was introduced to solve the above problem. The spectrum is decomposed into a series of modes (uk) by VMD. Then, the high-frequency noise modes are removed and the remaining modes are reconstructed to obtain the denoised spectrum. The proposed method was verified by two artificial noised signals and two Raman spectra of inorganic materials, i.e., MnCo ISAs/CN and Fe-NCNT. For comparison, empirical mode decomposition (EMD), Savitzky-Golay (SG) smoothing, and discrete wavelet transformation (DWT) are also investigated. At the same time, signal-to-noise ratio (SNR) was introduced as evaluation indicators to verify the performance of the proposed method. The results show that compared with EMD, VMD can significantly improve mode mixing and the endpoint effect. Moreover, the Raman spectrum by VMD denoising is more excellent than that of EMD, SG smoothing and DWT in terms of visualization and SNR. For the small sharp peaks, some information is lost after denoising by EMD, SG smoothing, DWT and VMD while VMD loses fewest information. Therefore, VMD may be an alternative method for Raman spectral denoising.

4.
Front Chem ; 10: 949461, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36110141

RESUMO

Due to the influence of uncontrollable factors such as the environment and instruments, noise is unavoidable in a spectral signal, which may affect the spectral resolution and analysis result. In the present work, a novel spectral denoising method is developed based on the Hilbert-Huang transform (HHT) and F-test. In this approach, the original spectral signal is first decomposed by empirical mode decomposition (EMD). A series of intrinsic mode functions (IMFs) and a residual (r) are obtained. Then, the Hilbert transform (HT) is performed on each IMF and r to calculate their instantaneous frequencies. The mean and standard deviation of instantaneous frequencies are calculated to further illustrate the IMF frequency information. Third, the F-test is used to determine the cut-off point between noise frequency components and non-noise ones. Finally, the denoising signal is reconstructed by adding the IMF components after the cut-off point. Artificially chemical noised signal, X-ray diffraction (XRD) spectrum, and X-ray photoelectron spectrum (XPS) are used to validate the performance of the method in terms of the signal-to-noise ratio (SNR). The results show that the method provides superior denoising capabilities compared with Savitzky-Golay (SG) smoothing.

5.
Br J Radiol ; 95(1134): 20210768, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35262392

RESUMO

OBJECTIVE: To explore the correlation between radiomic features and the pathology of pure ground-glass opacities (pGGOs), we established a radiomics model for predicting the pathological subtypes of minimally invasive adenocarcinoma (MIA) and precursor lesions. METHODS: CT images of 1521 patients with lung adenocarcinoma or precursor lesions appearing as pGGOs on CT in our hospital (The Third Affiliated Hospital of Sun Yat-sen University) from January 2015 to March 2021 were analyzed retrospectively and selected based on inclusion and exclusion criteria. pGGOs were divided into an atypical adenomatous hyperplasia (AAH)/adenocarcinoma in situ (AIS) group and an MIA group. Radiomic features were extracted from the original and preprocessed images of the region of interest. ANOVA and least absolute shrinkage and selection operator feature selection algorithm were used for feature selection. Logistic regression algorithm was used to construct radiomics prediction model. Receiver operating characteristic curves were used to evaluate the classification efficiency. RESULTS: 129 pGGOs were included. 2107 radiomic features were extracted from each region of interest. 18 radiomic features were eventually selected for model construction. The area under the curve of the radiomics model was 0.884 [95% confidence interval (CI), 0.818-0.949] in the training set and 0.872 (95% CI, 0.756-0.988) in the test set, with a sensitivity of 72.73%, specificity of 88.24% and accuracy of 79.47%. The decision curve indicated that the model had a high net benefit rate. CONCLUSION: The prediction model for pathological subtypes of MIA and precursor lesions in pGGOs demonstrated a high diagnostic accuracy. ADVANCES IN KNOWLEDGE: We focused on lesions appearing as pGGOs on CT and revealed the differences in radiomic features between MIA and precursor lesions. We constructed a radiomics prediction model and improved the diagnostic accuracy for the pathology of MIA and precursor lesions.


Assuntos
Adenocarcinoma , Neoplasias Pulmonares , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Invasividade Neoplásica , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
6.
Nanotechnology ; 33(40)2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35245913

RESUMO

S-doped Fe/Ni oxide and Fe/Ni hydride oxide catalysts exhibit good oxygen evolution reaction (OER) performance. Nevertheless, the over-doping of S and the agglomeration of active sites still hinder the improvement of the performance of these catalysts. The S/O ratio regulation can optimize the electronic structure effectively so as to improve the OER performance of the catalysts, but few studies have focused on this study. Here, we find a facile room-temperature method to synthesize the unique 3D ultra-thin FeNiOS nanosheets with an adjustable S/O ratio for OER. The FeNiOS-NS catalysts exhibit excellent OER performance with an overpotential of 235 mV at 10 mA cm-2and a small Tafel slope of 64.2 mV dec-1in 0.1 M KOH, which originated from the sufficient exposure of the active Fe-Ni component and the optimized electronic structure due to the tunable S/O ratio. This study demonstrates a novel strategy to optimize the OER performance of Ni-based catalysts.

7.
Breastfeed Med ; 16(12): 938-946, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34813377

RESUMO

Objective: To investigate the effects of breastfeeding (BF) on metabolic-related outcomes in women with previous gestational diabetes mellitus. Methods: Databases, including PubMed, Embase, Cochrane Library, and Web of Science, were searched until March 5, 2020. Finally, 14 high-quality articles were included. Relative risk (RR) and weighted mean difference (WMD) with 95% confidence interval (CI) were pooled using Stata14.0 Software. Results: Subjects in the BF group had a lower incidence of diabetes (RR: 0.611, 95% CI: 0.452-0.826, p < 0.001) and lower fasting plasma glucose level (WMD: -4.762, 95% CI: -5.552 to -3.973, p < 0.001), fasting insulin level (WMD: -21.513, 95% CI: -37.594 to -5.431, p = 0.009), homeostasis model assessment of insulin resistance (HOMA-IR) (WMD: -1.107, 95% CI: -1.683 to -0.532, p < 0.001), and triglyceride level (WMD: -33.951, 95% CI: -50.714 to -17.189, p < 0.001) than those in the non-BF group. The high-density lipoprotein level (WMD: 3.855, 95% CI: 2.629-5.081, p < 0.001), low-density lipoprotein level (WMD: 4.223, 95% CI: 0.6712-7.774, p = 0.020), and insulin sensitivity index (WMD: 1.503, 95% CI: 0.857-2.160, p < 0.001) in the BF group were higher than that in the non-BF group. No difference was found in the 2-hour postprandial blood glucose (WMD: -3.804, 95% CI: -8.237 to 0.630, p = 0.093), incidence of prediabetes mellitus (RR: 0.870, 95% CI: 0.750-1.009, p = 0.065), or cholesterol level (WMD: 1.377, 95% CI: -8.178 to 10.931, p = 0.778) between the two groups. Conclusion: BF may improve several metabolic markers and decrease the risk of developing diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Biomarcadores , Glicemia/metabolismo , Aleitamento Materno , Diabetes Gestacional/epidemiologia , Feminino , Humanos , Gravidez
9.
Autophagy ; 17(7): 1684-1699, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-32543267

RESUMO

Macroautophagy/autophagy is a membrane-mediated intracellular degradation pathway, through which bulky cytoplasmic content is digested in lysosomes. How the autophagy initiation and maturation steps are regulated is not clear. In this study, we found an E3 ubiquitin ligase complex, linear ubiquitin chain assembly complex (LUBAC) and a deubiquitinating enzyme (DUB) OTULIN localize to the phagophore area to control autophagy initiation and maturation. LUBAC key component RNF31/HOIP translocates to the LC3 puncta area when autophagy is induced. RNF31 knockdown inhibits autophagy initiation, and cells are more sensitive to bacterial infection. OTULIN knockdown, however, promotes autophagy initiation but blocks autophagy maturation. In OTULIN knockdown cells, excessive ubiquitinated ATG13 protein was recruited to the phagophore for prolonged expansion, and therefore inhibits autophagosome maturation. Together, our study provides evidence that LUBAC and OTULIN cooperatively regulate autophagy initiation and autophagosome maturation by mediating the linear ubiquitination and the stabilization of ATG13.Abbreviations: ATG: autophagy-related; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CQ: chloroquine; CUL1-FBXL20: cullin 1-F-box and leucine rich repeat protein 20; CUL3-KLHL20: cullin 3-kelch like family member 20; CUL4-AMBRA1: cullin 4-autophagy and beclin 1 regulator 1; CYLD: CYLD lysine 63 deubiquitinase; DAPI: 4',6-diamidino-2-phenylindole; DUB: deubiquitinating enzyme; EBSS: Earle's Balanced Salt Solution; GFP: green fluorescent protein; GST: glutathione S-transferase; IKBKG/NEMO: inhibitor of nuclear factor kappa B kinase regulatory subunit gamma; LUBAC: linear ubiquitin chain assembly complex; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3B; MIM: MIT-interacting motif; mRFP: monomeric red fluorescent protein; NEDD4: NEDD4 E3 ubiquitin protein ligase; NFKB: NF-kappaB complex; OPTN: optineurin; OTULIN: OTU deubiquitinase with linear linkage specificity; PIK3C3/Vps34: phosphatidylinositol 3-kinase catalytic subunit type 3; PtdIns: phosphatidylinositol; PtdIns3K: class III phosphatidylinositol 3-kinase complex; PtdIns3P: phosphatidylinositol 3-phosphate; RBCK1/HOIL1: RANBP2-type and C3HC4-type zinc finger containing 1; RB1CC1/FIP200: RB1-inducible coiled-coil 1; RIPK1: receptor interacting serine/threonine kinase 1; RNF216: ring finger protein 216; RNF31/HOIP: ring finger protein 31; RT-PCR: reverse transcriptase polymerase chain reaction; S. Typhimurium: Salmonella enterica serovar Typhimurium; SHARPIN: SHANK associated RH domain interactor; SMURF1: SMAD specific E3 ubiquitin protein ligase 1; SQSTM1: sequestosome 1; STING: stimulator of interferon response cGAMP interactor 1; STUB1/CHIP: STIP1 homology and U-box containing protein 1; TNF/TNF-alpha: tumor necrosis factor; TNFAIP3/A20: TNF alpha induced protein 3; TRAF6: TNF receptor associated factor 6; TRIM32: tripartite motif containing 32; UBAN: ubiquitin binding in TNIP/ABIN and IKBKG/NEMO proteins; ULK1/2: unc-51 like autophagy activating kinase 1/2; USP: ubiquitin specific peptidase; UVRAG: UV radiation resistance associated; VCPIP1: valosin containing protein interacting protein 1; WIPI2: WD repeat domain, phosphoinositide interacting protein 2; ZBTB16-CUL3-RBX1: zinc finger and BTB domain containing protein 16-cullin 3-ring-box 1; ZRANB1: zinc finger RANBP2-type containing 1.


Assuntos
Autofagia , Endopeptidases/metabolismo , Complexos Ubiquitina-Proteína Ligase/metabolismo , Endopeptidases/fisiologia , Técnicas de Silenciamento de Genes , Células HEK293 , Células HeLa , Humanos , Microscopia de Fluorescência , Complexos Ubiquitina-Proteína Ligase/fisiologia , Ubiquitinação
10.
iScience ; 23(11): 101708, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33241194

RESUMO

AMFR/gp78 and USP13 are a pair of ubiquitin ligase and deubiquitinase that ensure the accuracy of endoplasmic reticulum-associated degradation (ERAD). Depletion of USP13 leads to caspase activation and cleavage of the ERAD chaperone BAG6, which is reversed by knockdown of AMFR. However, the mechanism and physiological relevance of this regulation are still unclear. Here, by using the NEDDylator system, we screened out TXN as a substrate of AMFR and USP13 and showed its involvement in regulating CASP3 activation and BAG6 cleavage. Furthermore, we showed that the cleaved N-terminal BAG6 is located in the cytosol and interacts with both LC3B-I and unprocessed form of LC3B (Pro-LC3B) through the LIR1 motif to suppress autophagy. An NMR approach verified the direct interaction between BAG6 LIR1 and LC3B-I or Pro-LC3B. Collectively, our findings uncover a mechanism that converts BAG6 from an ERAD regulator to an autophagy tuner and apoptosis inducer during ER stress.

11.
J Exp Clin Cancer Res ; 39(1): 52, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32197643

RESUMO

BACKGROUND: Runt-related transcription factor 1 (RUNX1) is a heterodimeric transcription factor that binds to the core element of many enhancers and promoters and can accelerate apoptosis in various tumors. However, the regulatory mechanisms underlying RUNX1 expression in neuroblastoma (NB), a highly malignant tumor in childhood, remain largely unclear. In this study, we aimed to assess the role of RUNX1 in NB and to reveal the underlying mechanisms that may contribute to finding a potential therapeutics strategy against NB. METHODS: Growth, invasion, metastasis and angiogenesis were assessed using Cell Counting Kit-8 (CCK-8) immunocytochemistry, and studies involving soft agar, cell invasion, tube formation and whole animals. The levels of expression were measured using real-time quantitative PCR for RNA, Western blot and immunostaining analyses for proteins. Luciferase reporter and chromatin immunoprecipitation assays indicated that RUNX1 directly binds within the BIRC5, CSF2RB and NFKBIA promoter regions to facilitate transcription. The level of apoptosis was assessed by determining mitochondrial membrane potential and flow cytometry. RESULTS: RUNX1 was highly expressed in ganglioneuroma (GN) and well-differentiated (WD) tissues relative to the poorly differentiated (PD) and undifferentiated (UD) ones. Moreover, RUNX1 effectively reduced cell viability, invasion, metastasis, angiogenesis, and promoted apoptosis in vitro and in vivo. RUNX1 reduced BIRC5 transcription and increased CSF2RB and NFKBIA transcription by directly binding BIRC5, CSF2RB and NFKBIA promoters. In addition, cytotoxic drugs, especially cisplatin, significantly increased RUNX1 expression in NB cells and promoted apoptosis. CONCLUSIONS: These data show that RUNX1 is an independent surrogate marker for the progression of NB and it can be used for monitoring NB prognosis during therapy.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core/genética , Neuroblastoma/genética , Animais , Apoptose/fisiologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Subunidade alfa 2 de Fator de Ligação ao Core/biossíntese , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Progressão da Doença , Feminino , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Neuroblastoma/irrigação sanguínea , Neuroblastoma/metabolismo , Neuroblastoma/patologia
12.
BMC Med Educ ; 18(1): 234, 2018 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-30305087

RESUMO

BACKGROUND: Development assistance for health (DAH) is an important component of foreign assistance. International health consultants usually play a key role in the international DAH field. However, there is still a shortage of consulting training in China. To address this issue and develop new backup force of DAH for China, the Global Health Institute of Wuhan University (GHIWHU) launched a training program called the "Consulting Training Course for International Development Assistance for Health". The purpose of this article is to evaluate the impact of the training on participants. METHODS: We conducted the analysis using Kirkpatrick's model. An evaluation survey examining participants' reaction (level 1) and learning (level 2) was carried out among trainees following the training, and a follow-up telephone interview of application (level 3) was made in three months after the training. RESULTS: A total of 25 participants from Chinese Consortium of Universities for Global Health (CCUGH) attended the training program. Results of satisfaction evaluation indicated that the training program was well received, with more than 85% of participants felt satisfied or relatively satisfied with the training. Trainees' self-ratings of the consulting knowledge and skills showed a significant increase (p < 0.001) from pre- to post-training. The follow-up interview revealed that the majority of participants applied the acquired knowledge and skills under various circumstances such as consulting program, teaching processes, writing reports, and et al. Meanwhile, participants considered that the lack of opportunities was one of the major application barriers. In addition, they expressed the willingness to participate in more relevant training and the need for more practice opportunities. CONCLUSIONS: This is the first study evaluating a consulting training program in China. The results show that the training course has been successfully implemented and participants have been given consulting knowledge and skills. Future research should use better-designed training methods based on demand surveys and consider providing participants with practice or practicum opportunities. Also, it is necessary to conduct both primary and advanced training courses and evaluate participants' long-term behavior changes resulting from the training.


Assuntos
Educação Médica , Saúde Global , Pessoal de Saúde/educação , Cooperação Internacional , Encaminhamento e Consulta , China , Países em Desenvolvimento , Humanos , Modelos Educacionais , Avaliação de Programas e Projetos de Saúde
13.
J Hazard Mater ; 356: 53-60, 2018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-29807239

RESUMO

Removal of toxic organics and bacterial disinfection are important tasks in wastewater treatment. Most heavy metal-based catalysts for degradation of aqueous organic pollutants in heterogeneous Fenton-like processes suffer from the toxicity of leached metals. The present work reports environmentally benign systems for both degradation of organics and bacterial disinfection. Calcium substituted LaFeO3-δ perovskite was demonstrated as an efficient catalyst to activate peroxymonosulfate (PMS) for degradation of phenol, methylene blue and rhodamine 6 G. Compared to LaFeO3-δ and nanocrystal Fe3O4, the lattice oxygen vacancies in B-site cation-deficient perovskite of La0.8Ca0.2Fe0.94O3-δ (LaCaFeO3-δ) particles renders this material a greatly improved catalytic performance. Electron paramagnetic resonance (EPR) suggested that both sulfate (SO4-) and hydroxyl radicals (OH) played critical roles in the advanced oxidation processes. Moreover, silver doped perovskite (Ag-LaCaFeO3-δ)/PMS successfully inhibited the growth of waterborne pathogen Escherichia coli and Methicillin-resistant Staphylococcus aureus (MRSA) at a lower dose than silver ions, proving a synergetic effect between free radicals and Ag+ in killing the bacteria. Therefore, Ag-LaCaFeO3-δ/PMS would be promising for practical wastewater treatment.


Assuntos
Compostos de Cálcio , Ferro , Lantânio , Óxidos , Peróxidos/química , Prata , Titânio , Compostos de Cálcio/química , Compostos de Cálcio/farmacologia , Catálise , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Ferro/química , Ferro/farmacologia , Lantânio/química , Lantânio/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Azul de Metileno/química , Óxidos/química , Óxidos/farmacologia , Prata/química , Prata/farmacologia , Titânio/química , Titânio/farmacologia , Poluentes da Água/química , Purificação da Água/métodos
14.
Materials (Basel) ; 11(2)2018 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-29425163

RESUMO

Based on the fluorescence resonance energy transfer (FRET) mechanism, fluorescent DNA probes were prepared with a novel DNA hairpin template method, with SiO2 coated CdTe (CdTe/SiO2) core/shell nanoparticles used as the fluorescence energy donors and gold (Au) nanoparticles (AuNPs) as the energy acceptors. The nanostructure and energy donor/acceptor ratio in a probe were controlled with this method. The relationship between the nanostructure of the probes and FRET efficiency (quenching efficiency) were investigated. The results indicated that when the donor/acceptor ratios were 2:1, 1:1, and 1:2; the corresponding FRET efficiencies were about 33.6%, 57.5%, and 74.2%, respectively. The detection results indicated that the fluorescent recovery efficiency of the detecting system was linear when the concentration of the target DNA was about 0.0446-2.230 nmol/L. Moreover, the probes showed good sensitivity and stability in different buffer conditions with a low detection limit of about 0.106 nmol/L.

15.
Environ Toxicol ; 33(5): 587-593, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29436100

RESUMO

Colorectal cancer (CRC) is one of the most common cancers and causes of cancer-related death. There are several first-line chemotherapeutic drugs used to treat CRC. Oxaliplatin (OXA) is an alkylating cytotoxic agent that is usually combined with other chemotherapeutic drugs to treat stage II and stage III CRC. However, cancer cells commonly acquire multidrug resistance (MDR), which is a major obstruction to cancer treatment. Recent studies have shown that natural components from traditional Chinese medicine or foods that have many biological functions may be new adjuvant therapies in clinical trials. We challenged LoVo CRC cell lines with OXA in a dose-dependent manner to create an OXA-resistant model. The expression of ABCG2 was significantly higher, and levels of endoplasmic reticulum (ER) stress markers were lower than those Parental cells. However, Lupeol, which is found in fruits and vegetables, has been shown to have bioactive properties, including anti-tumor properties that are relevant to many diseases. In our study, Lupeol downregulated cell viability and activated cell apoptosis. Moreover, Lupeol decreased the expression of ABCG2 and activated ER stress to induce OXA-resistant cell death. Importantly, the anti-tumor effect of Lupeol in OXA-resistant cells was higher than that of LoVo Parental cells. In addition, we also confirmed our results with a xenograft animal model, and the tumor size significantly decreased after Lupeol injections. Our findings show that Lupeol served as a strong chemoresistant sensitizer and could be a new adjuvant therapy method for chemoresistant patients.


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Apoptose/efeitos dos fármacos , Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Estresse do Retículo Endoplasmático , Proteínas de Neoplasias/genética , Compostos Organoplatínicos/uso terapêutico , Triterpenos Pentacíclicos/farmacologia , Animais , Apoptose/genética , Morte Celular/efeitos dos fármacos , Morte Celular/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Resistencia a Medicamentos Antineoplásicos/genética , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Estresse do Retículo Endoplasmático/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Camundongos Nus , Oxaliplatina , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Biochem Biophys Res Commun ; 497(2): 726-733, 2018 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-29462615

RESUMO

Ubiquitination modification has been shown to play a key role in autophagy. Increasing studies reported the involvement of de-ubiquitinating enzymes (DUBs) in autophagy pathway. To systematically search how DUBs manipulate autophagy, we utilized a double fluorescence tagged LC3 stable HeLa cell line, and did a genome wide screen of 55 human DUBs which is about 60% coverage of the DUB family. We found a bunch of DUBs have impact on autophagy by either changing the LC3 puncta formation or the autophagy flux. One of them, Ubiquitin C-Terminal Hydrolase L1 (UCHL1) correlated to Parkinson's disease, strongly affects autophagy by inhibiting autophagosome formation. We found UCHL1 overexpression inhibits LC3 puncta formation and is dependent on its DUB activity. Knockdown of UCHL1 significantly promotes LC3 puncta formation. Further study revealed that UCHL1 may affect autophagy by interacting with LC3 but not other autophagy related proteins. Interestingly, a Parkinson's disease related mutant UCHL1 I93 M defects its DUB activity and can no longer inhibit autophagosome formation. We further screened 22 commercially available DUB inhibitors and found two potent UCHL1 inhibitors LDN-57444 (LDN) and NSC632839 (NSC), when treating cells, both strongly induce LC3 puncta formation. Taken together, our results indicated a new insight into the manner in which DUB regulates autophagy and provided potential drugs for the Parkinson's disease.


Assuntos
Autofagossomos/metabolismo , Autofagia , Ubiquitina Tiolesterase/metabolismo , Técnicas de Silenciamento de Genes , Células HeLa , Humanos , Ubiquitina/metabolismo , Ubiquitina Tiolesterase/genética , Ubiquitinação
17.
Environ Pollut ; 227: 596-605, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28457735

RESUMO

An increasing number of studies have been conducted to determine a possible linkage between maternal exposure to ambient fine particulate matter and effects on the developing human fetus that can lead to adverse birth outcomes, but, the present results are not consistent. A total of 23 studies published before July 2016 were collected and analyzed and the mean value of reported exposure to fine particulate matter (PM2.5) ranged from 1.82 to 22.11 We found a significantly increased risk of preterm birth with interquartile range increase in PM2.5 exposure throughout pregnancy (odds ratio (OR) = 1.03; 95% conditional independence (CI): 1.01-1.05). The pooled OR for the association between PM2.5 exposure, per interquartile range increment, and term low birth weight throughout pregnancy was 1.03 (95% CI: 1.02-1.03). The pooled ORs for the association between PM2.5 exposure per 10 increment, and term low birth weight and preterm birth were 1.05 (95% CI: 0.98-1.12) and 1.02 (95% CI: 0.93-1.12), respectively throughout pregnancy. There is a significant heterogeneity in most meta-analyses, except for pooled OR per interquartile range increase for term low birth weight throughout pregnancy. We here show that maternal exposure to fine particulate air pollution increases the risk of preterm birth and term low birth weight. However, the effect of exposure time needs to be further explored. In the future, prospective cohort studies and personal exposure measurements needs to be more widely utilized to better characterize the relationship between ambient fine particulate exposure and adverse birth outcomes.


Assuntos
Poluição do Ar/estatística & dados numéricos , Recém-Nascido de Baixo Peso , Exposição Materna/estatística & dados numéricos , Material Particulado/análise , Nascimento Prematuro/epidemiologia , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Peso ao Nascer/efeitos dos fármacos , Feminino , Humanos , Recém-Nascido , Exposição Materna/efeitos adversos , Razão de Chances , Gravidez , Estudos Prospectivos , Risco
18.
Sci Rep ; 7: 40482, 2017 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-28084399

RESUMO

Few studies have compared different methods when exploring the short-term effects of air pollutants on respiratory disease mortality in Wuhan, China. This study assesses the association between air pollutants and respiratory disease mortality with both time-series and time-stratified-case-crossover designs. The generalized additive model (GAM) and the conditional logistic regression model were used to assess the short-term effects of air pollutants on respiratory disease mortality. Stratified analyses were performed by age, sex, and diseases. A 10 µg/m3 increment in SO2 level was associated with an increase in relative risk for all respiratory disease mortality of 2.4% and 1.9% in the case-crossover and time-series analyses in single pollutant models, respectively. Strong evidence of an association between NO2 and daily respiratory disease mortality among men or people older than 65 years was found in the case-crossover study. There was a positive association between air pollutants and respiratory disease mortality in Wuhan, China. Both time-series and case-crossover analyses consistently reveal the association between three air pollutants and respiratory disease mortality. The estimates of association between air pollution and respiratory disease mortality from the case-crossover analysis displayed greater variation than that from the time-series analysis.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Doenças Respiratórias/mortalidade , Idoso , China/epidemiologia , Estudos Cross-Over , Feminino , Humanos , Umidade , Masculino , Pessoa de Meia-Idade , Dióxido de Nitrogênio/análise , Material Particulado/análise , Dióxido de Enxofre/análise , Temperatura , Fatores de Tempo
19.
Oncotarget ; 8(9): 16017-16026, 2017 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-27926481

RESUMO

Recent evidence indicates that metformin therapy may be associated with a decreased colorectal adenoma/colorectal cancer risk in type 2 diabetes patients. However, results are not consistent. We therefore performed a systematic review and meta-analysis to assess the association between metformin therapy and risk of colorectal adenomas/colorectal cancer in type 2 diabetes mellitus patients. We searched the literature published before Aug 31, 2016 in four databases: PubMed, Embase database, CNKI and VIP Library of Chinese Journal. Summary risk estimates (adjusted OR/adjusted RR/adjusted HR) with their 95% confidence interval (95% CI) were obtained using a random effects model. Twenty studies (including 12 cohort studies, 7 case-control studies and 1 randomized controlled trial study) were selected in terms of data of colorectal adenomas or colorectal cancer incidence. Metformin therapy was found to be associated with a decreased incidence of colorectal adenomas (unadjusted OR=0.80, 95% CI: 0.71-0.90, p=0.0002). When the adjusted data were analyzed, the summary estimate decreased to 25% reduction in colorectal adenomas risk (adjusted OR=0.75, 95% CI: 0.59-0.97, p=0.03). Besides, a significant reduction of colorectal cancer risk was also observed (unadjusted OR=0.73, 95% CI: 0.62-0.86, p=0.0002). And when the adjusted data were analyzed, colorectal cancer risk for metformin users was decreased with a reduction of 22%, compared with non-metformin users and other treatment users (adjusted OR=0.78, 95% CI: 0.70-0.87, p<0.00001). Our meta-analysis suggested that metformin therapy may be associated with a decreased risk of colorectal adenomas and colorectal cancer in type 2 diabetes mellitus patients.


Assuntos
Adenoma/prevenção & controle , Neoplasias Colorretais/prevenção & controle , Diabetes Mellitus Tipo 2/complicações , Metformina/uso terapêutico , Humanos
20.
Artigo em Inglês | MEDLINE | ID: mdl-27571088

RESUMO

This study assessed the public's health risk awareness of urban air pollution triggered by three megacities in China, and the data are the responses from a sample size of 3868 megacity inhabitants from Shanghai, Nanchang and Wuhan. Descriptive analyses were used to summarize the respondents' demographics, perceived health risks from air pollution and sources of health-related knowledge on urban air pollution. Chi-square tests were used to examine if participants' demographics were associated with participant's general attitudes towards current air quality and the three perceived highest health risks due to urban air pollution. We found low rate of satisfaction of current urban air quality as well as poor knowledge of air pollution related indicator. Participants' gender, age and travel experience were found to be associated with the satisfaction of current air quality. The knowledge of air pollution related indicator was significantly affected by respondents' education, monthly income, health status, and sites of study. As many as 46.23% of the participants expressed their feelings of anxiety when exposed to polluted air, especially females, older adults and those with poor health conditions. Most participants believed that coughs/colds, eye problems and skin allergies were the three highest health risks due to urban air pollution based on public education through television/radio, internet and newspaper/magazine. Further public health education is needed to improve public awareness of air pollution and its effects.


Assuntos
Poluição do Ar/efeitos adversos , Conhecimentos, Atitudes e Prática em Saúde , Saúde Pública , Adolescente , Adulto , Idoso , Conscientização , China , Cidades , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Saúde Pública/estatística & dados numéricos , Risco , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA