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1.
J Transl Med ; 22(1): 579, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890720

RESUMO

BACKGROUND: This study developed a nomogram model using CT-based delta-radiomics features and clinical factors to predict pathological complete response (pCR) in esophageal squamous cell carcinoma (ESCC) patients receiving neoadjuvant chemoradiotherapy (nCRT). METHODS: The study retrospectively analyzed 232 ESCC patients who underwent pretreatment and post-treatment CT scans. Patients were divided into training (n = 186) and validation (n = 46) sets through fivefold cross-validation. 837 radiomics features were extracted from regions of interest (ROIs) delineations on CT images before and after nCRT to calculate delta values. The LASSO algorithm selected delta-radiomics features (DRF) based on classification performance. Logistic regression constructed a nomogram incorporating DRFs and clinical factors. Receiver operating characteristic (ROC) and area under the curve (AUC) analyses evaluated nomogram performance for predicting pCR. RESULTS: No significant differences existed between the training and validation datasets. The 4-feature delta-radiomics signature (DRS) demonstrated good predictive accuracy for pCR, with α-binormal-based and empirical AUCs of 0.871 and 0.869. T-stage (p = 0.001) and differentiation degree (p = 0.018) were independent predictors of pCR. The nomogram combined the DRS and clinical factors improved the classification performance in the training dataset (AUCαbin = 0.933 and AUCemp = 0.941). The validation set showed similar performance with AUCs of 0.958 and 0.962. CONCLUSIONS: The CT-based delta-radiomics nomogram model with clinical factors provided high predictive accuracy for pCR in ESCC patients after nCRT.


Assuntos
Quimiorradioterapia , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Terapia Neoadjuvante , Nomogramas , Curva ROC , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/diagnóstico por imagem , Resultado do Tratamento , Idoso , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/diagnóstico por imagem , Reprodutibilidade dos Testes , Adulto , Área Sob a Curva , Estudos Retrospectivos , Radiômica
2.
Heliyon ; 9(9): e19317, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37662759

RESUMO

The purpose of this study was to develop a bio-mechanical pulp from rice straw with thermal and low chemical dosage. The process is carried out by thermal alkali kneading pretreatment (0-5% NaOH) with a high concentration kneader, enzyme pretreatment (0.2-4%) and Hollander beater. The results showed that the addition of NaOH was the main factor affecting the properties of pulp and paper, and the best properties of straw pulp could be obtained when NaOH and enzyme dosage were 5% and 0.2%, respectively. Although the optimum rice straw pulp is inferior to straw soda pulp in terms of tensile, burst and ring crush index, it is superior to old corrugated cardboard pulp and partially meets the CNS standards of corrugated medium paper and linerboard without the addition of chemicals. Therefore, the bio-mechanical rice straw pulp in this study has the potential to be produced as industrial paper.

3.
Chemosphere ; 312(Pt 1): 137293, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36403811

RESUMO

Standard reference materials (SRMs) have been commonly used to perform quality assurance and quality control (QA/QC) in soil total metal concentration analyses or bioaccessibility assessment. In this study, 10 experimenters from 4 laboratories determined bioaccessibility of lead (Pb) in 4 widely-used SRMs (NIST 2710a, NIST 2587, BGS 102, and GBW 07405). Based on the gastric phase (GP) of the unified BARGE bioaccessibility method (UBM) and the Solubility Bioavailability Research Consortium procedure (SBRC), Pb bioaccessibility in SRMs was compared within and between laboratories to assess their intra-laboratory repeatability and inter-laboratory reproducibility. Lead bioaccessibility was 14.1 ± 2.44%-101 ± 2.48% in the 4 SRMs. The values were in vivo validated based on a mouse model in previous studies (R2 = 0.97-0.98), suggesting the reliability of Pb bioaccessibility data. Strong correlations were observed for Pb bioaccessibility among 7 experimenters (R2 = 0.94-0.99) at the Nanjing University (NJU) laboratory and similar strong correlations were also found between each two of the 4 laboratories (R2 = 0.94-0.98), illustrating consistency in intra- and inter-laboratory performance. The intra-laboratory repeatability and inter-laboratory reproducibility were generally acceptable with relative standard deviations (RSDs) of Pb bioaccessibility being ≤10% within laboratory and ≤20% between laboratories, except in a soil with low bioaccessible Pb (BSG 102). Our study suggested that measurements of Pb bioaccessibility in SRMs based on the two in vivo validated methods were repeatable and reproducible within and between laboratories, further verified their reliability being used as QA/QC samples during Pb bioaccessibility assessment.


Assuntos
Poluentes do Solo , Solo , Camundongos , Animais , Poluentes do Solo/análise , Reprodutibilidade dos Testes , Chumbo/análise , Disponibilidade Biológica
4.
Nanomaterials (Basel) ; 12(17)2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36080107

RESUMO

The spontaneous emission of a fluorophore is altered by the surrounding electromagnetic field. Therefore, the radiation of the fluorophore can be engineered by inter-coupling with the nanoscale plasmons. This work proposes a nanoscale hemisphere structure that enhances the electric field and further modulates its effects on fluorophores by adjusting the radius of the hemisphere. A full-wave simulation is carried out using the finite element method, and the radiation characteristics of the nanoscale hemisphere are studied in detail. Compared with free space, the structure has generated significant enhancement exceeding 30. Through curve fitting, the relationship between the enhanced peak wavelength and the radius of the hemisphere is obtained.

5.
J Oncol ; 2022: 1533779, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35813859

RESUMO

Liensinine is a bioactive component of Plumula Nelumbinis extracted from the green embryo of the mature seeds of Nelumbonaceae and exhibits therapeutic functions and noteworthy anti-tumor effects in recent studies. However, the potential anti-tumor property and the underlying mechanisms of liensinine in nonsmall-cell lung cancer (NSCLC) have not been illustrated. In this study, we demonstrated that liensinine has the potential anti-tumor property, and it could inhibit growth of NSCLC in vitro and in vivo. In addition, we found that although it induced significant accumulation of autophagosomes, liensinine could quench them for degradation and blocked autophagic flux. Importantly, we observed that liensinine inhibited the normal function of mitochondrial energy supply and impaired the lysosomal function. This research firstly provides a possibility insight that liensinine could be a novel therapeutic strategy for NSCLC.

6.
Sci Rep ; 12(1): 3493, 2022 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-35241751

RESUMO

In this study, we separately used a laboratory Hollander beater, a pilot scale 12″ single-disc refiner and an expanded trial with a commercial paper mold mill to investigate the feasibility of using thermal-alkali/enzyme pretreated rice straw semi-chemical mechanical pulp to substitute portions of old corrugated carton board (OCC) pulp in the paper industry. In the laboratory plan, sequential treatments of NaOH at a 5-10% dosage and enzymes at a 0.2-4% dosage were applied to rice straw, followed by beating using a Hollander beater for 1-2 h to complete the rice straw semi-chemical mechanical pulping process. When the NaOH dosage, enzyme dosage and refining time were 10%, 0.2% and 1 h, the best quality rice straw pulp was obtained. Along with the increase in NaOH dosage, the pulp freeness decreased significantly, and the pulp accepted rate increased. Enzymatic treatment enhanced rice straw quality only after NaOH dosage treatment, which then reacted with rice straw to increase the quality of pulp. In the expanded trial, the rice straw semi-chemical mechanical pulp was blended with OCC pulp (0%, 25%, 50%, 75% and 100%) to form handsheets. Along with an increase in rice straw proportions, the tensile index, burst index, and ring-crush index increased by 109-200%, 13-196%, and 124-187%, respectively. In an online commercial paper mold mill trial, blending rice straw pulp with OCC could successfully make paper-mold egg cartons, with both mill operation and product smoothness appearance being highly acceptable.


Assuntos
Álcalis , Oryza , Estudos de Viabilidade , Hidróxido de Sódio
7.
Chemosphere ; 288(Pt 3): 132655, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34710465

RESUMO

To understand how Cd in different fractions contributes to Cd bioaccessibility by in vitro assays, Cd bioaccessibility in 12 contaminated soils was determined by four assays (UBM, SBRC, IVG, and PBET) and correlated with different Cd fractions based on a sequential extraction scheme. The Cd bioaccessibility in the gastric phase (GP) was high (35-107%, averaging at 77%), implicating high risk to human health, while it decreased to 19-88% averaging at 47% in the intestinal phased (IP). From the GP to IP, the reduction of extractable Cd (0.45-48 mg kg-1) and Fe (118-3884 mg kg-1) showed significant correlation (R = 0.54-0.74) via UBM, SBRC, and IVG, suggesting co-precipitation with Fe and/or sorption onto Fe oxides maybe responsible for decrease in Cd bioaccessibility. Although Cd bioaccessibility varied among assays, their results show some consistency based on their correlation in the GP (R = 0.56-0.90) and IP (0.34-0.73, excluding UBM-IP and PBET-IP). Sequential extraction data show that Cd was primarily associated with the exchangeable fraction (E1; 7.05-72.9%, averaging 39.4%). The carbonate (C2; 6.86-44.8%, 21.9%) and Fe/Mn oxides fraction (F3; 12.5-53.6%, 28.2%) were similar, while organic (O4; 0.62-25.0%, 7.91%) and residual fraction (R5; 0.22-8.54%, 2.62%) were the lowest. Significant correlation (R = 0.59-0.88) between the first two fractions (E1+C2) and bioaccessible Cd suggest they were the main sources of bioaccessible Cd in those contaminated soils.


Assuntos
Cádmio , Poluentes do Solo , Bioensaio , Disponibilidade Biológica , Poluição Ambiental , Humanos , Solo , Poluentes do Solo/análise
8.
Cancer Cell Int ; 21(1): 531, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34641863

RESUMO

BACKGROUND: The role of Diphenyldifluoroketone (EF24), a synthetic analogue of curcumin with noteworthy antitumor potential, remains unclear in non-small cell lung cancer (NSCLC). Herein, the inhibitory effect of EF24 on NSCLC and its mechanism were studied. METHODS: Cytotoxicity was measured by MTT assay, colony formation assay and xenograft model. Cell apoptosis and reactive oxygen species (ROS) level were quantified by flow cytometer. Protein level was detected by western blot assay. Mitochondria and autophagosomes were observed using transmission electron microscope and confocal microscopy. RESULTS: In-vitro, EF24 significantly induced proliferation inhibition, apoptosis, mitochondrial fission and autophagy of NSCLC cell lines. These cytotoxic effects were significantly attenuated by two reactive oxygen species (ROS) scavengers, indicating its anti-cancer effects largely depend on ROS accumulation. In-vivo, EF24 inhibited tumor growth in a dose-dependent manner. Moreover, no pathological changes of heart, lung, spleen, kidney and liver of mice were observed. Collectively, EF24 induced ROS accumulation, in turn activates cell apoptosis, and then exerts its cytotoxicity on NSCLC cells. CONCLUSIONS: The results showed that EF24 exerted cytotoxicity against NSCLC via ROS accumulation. Thus, EF24 might serve as a potential anti-cancer agent for the treatment of NSCLC.

9.
J Oncol ; 2021: 5538911, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34188681

RESUMO

TIPE1, a newly identified member in TIPE (TNFAIP8) family, plays an important role in tumorigenesis and immune regulation, but its role in ovarian cancer, especially in tumor metastasis, remains unknown. In the current study, we aimed to reveal the protein expression spectrum of TIPE1 in normal human tissues and explored its relationship with metastasis in ovarian cancer. The results of IHC staining showed that TIPE1 protein was not only detected in cytoplasm in most human tissues but also expressed in both cytoplasm and nucleus in squamous epithelium and some epithelial-derived cells with secretory functions, such as esophagus, cervix uteri and ovary, and thyroid gland. Moreover, TIPE1 protein was downregulated in ovarian cancer tissues compared with that in the paracancerous. More importantly, TIPE1 suppressed tumorigenesis and metastasis of ovarian cancer in vitro and in vivo, as evidence shows its ability to suppress growth, colony formation, migration, and epithelial-mesenchymal transition (EMT) of ovarian cancer. Taken together, our results demonstrate the suppressor role of TIPE1 in ovarian cancer metastasis, indicating TIPE1 might be a metastasis predictor and a novel therapeutic target for ovarian cancer.

10.
Bull Environ Contam Toxicol ; 107(5): 967-974, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34132817

RESUMO

In this study, soils spiked with copper oxide nanoparticles (CuO NPs) or Cu(NO3)2 and aged as long as 90 days were utilized to investigate effect of soil properties and aging on oral and inhalation bioaccessibility of CuO NPs. Results showed that oral bioaccessibility of CuO NPs in gastric phase (GP) ranged from 70% to 84%, it significantly decreased to 50%-70% in intestinal phase (IP). The inhalation bioaccessibility of CuO NPs in artificial lysosomal fluid (ALF) ranged from 66% to 85%, and much higher than that in Gamble's solution (GS, 3.3%-23%). By comparing CuO NPs to Cu(NO3)2 bioaccessibility, insignificant difference was found. The aging time (D15 and D90) had limited effect on their oral and inhalation bioaccessibility. CEC and free Al were positively and clay content was negatively correlated with CuO NPs inhalation bioaccessibility, while Cu(NO3)2 inhalation bioaccessibility decreased with increasing soil clay content and pH. Our findings provide an essential basis to evaluate the human health risks of CuO NPs.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Poluentes do Solo , Idoso , Cobre/análise , Humanos , Óxidos , Solo , Poluentes do Solo/análise
11.
Thorac Cancer ; 12(5): 659-666, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33474827

RESUMO

BACKGROUND: Despite the emerging insights into many snoRNAs (small nucleolar RNAs) which are detectable in body fluids and serve as noninvasive biomarkers, few studies have previously discussed the role of snoRNAs in tumor-educated platelets (TEPs). Herein, we systematically estimated dysregulation of snoRNAs in non-small cell lung cancer (NSCLC) and clarified the biomarker potential of SNORD55 in platelets. METHODS: We compared expression of snoRNAs between NSCLC and normal tissues using SNORic datasets. Platelets were isolated from plasma using low-speed centrifugation and subjected to quantitative polymerase chain reaction (qPCR) for SNORD55 detection. RESULTS: SNORD55 was significantly decreased in TEPs from NSCLC patients especially in early-stage patients compared with healthy controls. Importantly, we validated that TEP SNORD55 was capable of acting as a promising biomarker for NSCLC. It exerted diagnostic performance for NSCLC diagnosis, possessing an AUC of 0.803, as well as for early NSCLC diagnosis, possessing an AUC of 0.784. Moreover, the combination of TEP SNORD55 and carcinoembryonic antigen (CEA) improved the diagnostic efficiency of cancer progression. In addition, TEP SNORD55 also potentially acts as a noninvasive early biomarker for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) with favorable diagnostic efficiencies. CONCLUSIONS: In summary, TEP SNORD55 could potentially serve as a noninvasive biomarker for NSCLC diagnosis and early diagnosis. KEY POINTS: SNORD55 was significantly decreased in TEPs from NSCLC patients compared to healthy controls and acted as a novel biomarker for early NSCLC.


Assuntos
Biomarcadores Tumorais/metabolismo , Plaquetas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/sangue , Neoplasias Pulmonares/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino
12.
Thorac Cancer ; 12(4): 539-548, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33372399

RESUMO

BACKGROUND: Accumulating evidence shows that microRNAs are aberrantly expressed and exert essential roles in the tumorigenesis and tumor progression of non-small cell lung cancer (NSCLC). METHODS: The plasma miRNAs from five healthy donors and four NSCLC patients were profiled by miRNA microarray. The differentially expressed miRNAs from 154 primary NSCLC patients and 146 healthy donors were subjected to RNA isolation and verified by quantitative PCR (qPCR). RESULTS: The miRNA microarray analysis revealed that 40 differential miRNAs between NSCLC patients and healthy donors were selected. We found that the plasma miR-1247-5p, miR-301b-3p and miR-105-5p levels of patients were significantly higher than those of healthy controls. The receiver operating characteristic curve (ROC) analyses revealed higher area under the ROC curve (AUC) values and higher sensitivity/specificity of carcinoembryonic antigen (CEA) in combination with miR-1247-5p, miR-301b-3p, or miR-105-5p were superior to that of CEA alone. CONCLUSIONS: High miR-1247-5p, miR-301b-3p and miR-105-5p expression have been demonstrated to accelerate tumorigenesis, and these three miRNAs in plasma act as novel biomarkers for the early diagnosis of NSCLC patients. KEY POINTS: Plasma miR-1247-5p, miR-301b-3p and miR-105-5p act as novel biomarkers for early NSCLC and NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , MicroRNAs/sangue , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Casos e Controles , Detecção Precoce de Câncer , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade
13.
Chemosphere ; 256: 127163, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32470742

RESUMO

Seasonal changes in chemical compositions and source apportionment of PM2.5 during clear and hazy days help to develop effective control policy, but limited information is available in megacity Nanjing. In this study, 102 PM2.5 samples were collected during clear and hazy days from 4 seasons in 2014-2015. Their chemical compositions (organic and elemental carbon, 8 water-soluble ions, and 22 inorganic elements) were determined, which were used for PM2.5 source apportionment using the PMF model. The mean PM2.5 concentration was lower during clear days than hazy days (42 vs. 122 µg m-3), so were mean concentrations of metals (0.48 vs. 0.82 ng m-3 for Co and 2.0 vs. 2.4 µg m-3 for Na), water soluble ions (0.10 vs. 0.16 µg m-3 for Mg2+ and 12 vs. 23 µg m-3 for SO42-), and carbon species (3.2 vs. 5.4 µg m-3 for elemetal C and 20 vs. 35 µg m-3 for organic C). Based on the PMF model, five main sources of PM2.5 were identified including secondary aerosols (31%), coal combustion (27%), road & construction dust (26%), oil combustion (8.5%), and iron & steel industry (5.1%) for all samples. The PM2.5 concentrations from the 5 sources were 0.01-46.5, averaging 9.8 µg m-3 during clear days (PM2.5 < 75 µg m-3), which increased to 1.83-60.1, averaging 18 µg m-3 during hazy days. However, based on their contributions to PM2.5, only secondary aerosols increased during hazy days compared to clear days in all seasons (11 vs. 42%), indicating its dominant contribution to haze in Nanjing. For different seasons, road & construction dust was a major contributor to PM2.5 in the summer, while oil combustion (4.86 vs.16.8%) contributed more in spring. However, coal combustion became the main source of PM2.5 during the summer (44-85%) due to the pollution controls for the Youth Olympic Games. Our results suggest that secondary aerosols play an important role in haze formation and season-dependent pollution measures should be implemented for effective control of air pollution.


Assuntos
Aerossóis/análise , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Monitoramento Ambiental/métodos , Material Particulado/análise , Carbono/análise , China , Carvão Mineral/análise , Poeira/análise , Indústrias , Íons/análise , Estações do Ano , Aço , Emissões de Veículos/análise , Água/química , Tempo (Meteorologia)
14.
J Exp Clin Cancer Res ; 38(1): 239, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31174569

RESUMO

BACKGROUND: Temozolomide-perillyl alcohol conjugate (NEO212), a novel temozolomide (TMZ) analog, was previously reported to exert its anti-cancer effect in non-small cell lung cancer (NSCLC), and human nasopharyngeal carcinoma (NPC), etc.. In the current study, we intend to illuminate the potential anticancer property and the underly mechanisms of NEO212 in ovarian cancer cells. METHODS: The cytotoxicity of NEO212 was detected by MTT, colony formation analysis and xenograft model. The proteins involved in cell proliferation, DNA damage, autophagy and lysosomal function were detected by western blots; mitochondria, lysosome and autophagosome were visualized by TEM and/or immunofluorescence; Apoptosis, cell cycle analysis and mitochondrial transmembrane potential were detected by flow cytometry. TFEB translocation was detected by immunofluorescence and western blot. RESULTS: NEO212 has the potential anticancer property in ovarian cancer cells, as evidence from cell proliferation inhibition, G2/M arrest, DNA damage, xenograft, mitochondrial dysfunction and apoptosis. Importantly, we observed that although it induced significant accumulation of autophagosomes, NEO212 quenched GFP-LC3 degradation, down-regulated a series of lysosome related gene expression and blocked the autophagic flux, which significantly facilitated it induced apoptosis and was largely because it inhibited the nuclear translocation of transcription factor EB (EB). CONCLUSIONS: NEO212 inhibited TFEB translocation, and impaired the lysosomal function, implying NEO212 might avoid from autophagy mediated chemo-resistance, thus proposing NEO212 as a potential therapeutic candidate for ovarian cancer.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Dacarbazina/análogos & derivados , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neoplasias Ovarianas/metabolismo , Animais , Antineoplásicos/uso terapêutico , Autofagossomos/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Dano ao DNA/efeitos dos fármacos , Dacarbazina/farmacologia , Dacarbazina/uso terapêutico , Modelos Animais de Doenças , Feminino , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Mitocôndrias/ultraestrutura , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Transporte Proteico , Ensaios Antitumorais Modelo de Xenoenxerto
15.
J Exp Clin Cancer Res ; 37(1): 250, 2018 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-30326943

RESUMO

BACKGROUND: Temozolomide-perillyl alcohol conjugate (TMZ-POH), a novel Temozolomide (TMZ) analog developed based on the conjugation of TMZ and perillyl alcohol (POH), displayed strong anticancer potency in multiple cancer types. In this study, we aimed to clarify the relationship between TMZ-POH and autophagy, and explore the underlying mechanisms involved in. METHODS: The proteins involved in autophagy, mitochondrial fission, lysosomal function and membrane traffic were detected by western blots; Autophagosome, mitochondria and lysosome were visualized by transmission electron microscope (TEM) and immunostaining; Apoptosis analysis and fluorescence probe detection were applied by flow cytometry. RESULTS: TMZ-POH blocked mitophagy flux although the number of autophagosomes which colocalized with mitochondria in the cells was increased via inducing lysosomal dysfunction as evidence from impaired lysosomal acidification, maturation and hampered autophagosome- lysosome fusion, which largely depended on its downregulation on the small GTPase RAB7A via mevalonate pathway. More importantly, our data demonstrated TMZ-POH sensitized cancer cell to irradiation induced apoptosis. CONCLUSIONS: Temozolomide-perillyl alcohol conjugate impairs mitophagy flux by inducing lysosomal dysfunction in Non-Small Cell Lung Cancer (NSCLC) cells and sensitizes them to irradiation, thereby proposing TMZ-POH as a potential radiosensitizer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Lisossomos/efeitos dos fármacos , Monoterpenos/farmacologia , Radiossensibilizantes/farmacologia , Temozolomida/farmacologia , Antineoplásicos Alquilantes/farmacologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Humanos , Neoplasias Pulmonares/patologia , Mitofagia/efeitos dos fármacos , Mitofagia/efeitos da radiação , Monoterpenos/química , Temozolomida/química
16.
Cell Death Dis ; 9(2): 202, 2018 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-29426908

RESUMO

The DNA repair enzyme O6-methylguanin-DNA-methltransferase (MGMT) is able to remove products of alkylating agent such as O6-meG and emerges as a central determinant of cancer resistance to temozolomide (TMZ). Temozolomide-perillyl alcohol conjugate (TMZ-POH), a novel TMZ analog developed based on the conjugation of TMZ and POH, displayed strong anticancer potency in multiple cancer types, but seemed not to experience the chemoresistance even in cells with high MGMT expression unlike TMZ and other alkylating agents. In this study, we demonstrated TMZ-POH inhibited MGMT dependent on proteasomal pathway and this inhibition is a significant factor in its toxic effect in the non-small cell lung cancer (NSCLC) cells.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Monoterpenos/farmacologia , Temozolomida/farmacologia , Proteínas Supressoras de Tumor/metabolismo , Ubiquitinação/efeitos dos fármacos , Células A549 , Antineoplásicos Alquilantes/farmacologia , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Metilases de Modificação do DNA/antagonistas & inibidores , Enzimas Reparadoras do DNA/antagonistas & inibidores , Regulação para Baixo/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Monoterpenos/química , Complexo de Endopeptidases do Proteassoma/metabolismo , Temozolomida/química , Proteínas Supressoras de Tumor/antagonistas & inibidores
17.
J Agric Food Chem ; 62(20): 4625-31, 2014 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-24779966

RESUMO

Effects of asiatic acid (AA) at 10 or 20 mg/kg/day upon hepatic steatosis in mice consuming a high-fat diet (HFD) were examined. AA intake decreased body weight, water intake, feed intake, epididymal fat, and plasma and hepatic triglyceride levels in HFD-treated mice (P < 0.05). HFD enhanced 2.85-fold acetyl coenzyme A carboxylase (ACC1), 3.34-fold fatty acid synthase (FAS), 3.71-fold stearoyl CoA desaturase (SCD)-1, 3.62-fold 3-hydroxy-3-methylglutaryl coenzyme A reductase, 2.91-fold sterol regulatory element-binding protein (SREBP)-1c, and 2.75-fold SREBP-2 expression in liver (P < 0.05). Compared with HFD groups, AA intake at two doses reduced 18.9-45.7% ACC1, 25.1-49.8% FAS, 24.7-57.1% SCD-1, and 21.8-53.3% SREBP-1c protein expression (P < 0.05). Histological results indicated AA intake at two doses reduced hepatic lipid accumulation and inflammatory infiltrate. HFD increased hepatic production of reactive oxygen species, interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α, as well as decreased hepatic glutathione content and glutathione peroxidase and catalase activities (P < 0.05). AA intake at two doses reversed these alterations (P < 0.05). AA intake suppressed 32.4-58.8% nuclear factor kappa (NF-κ)B p65 and 24.2-56.7% p-p38 expression (P < 0.05) and at high dose down-regulated 29.1% NF-κB p50 and 40.7% p-JNK expression in livers from HFD-treated mice. AA intake at two doses lowered plasma insulin secretion and HOMR-IR (P < 0.05). These results suggest that AA is a potent hepatic protective agent against HFD-induced hepatic injury.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/prevenção & controle , Resistência à Insulina , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Triterpenos Pentacíclicos/farmacologia , Animais , Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Humanos , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/genética , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
18.
Mol Med Rep ; 10(1): 522-6, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24788223

RESUMO

The present study aimed to investigate faecal calprotectin as a diagnostic marker to differentiate between patients with inflammatory bowel disease (IBD) and those with irritable bowel syndrome (IBS). A total of 20 healthy control subjects, 26 patients with IBS and 58 patients with IBD, including 22 with ulcerative colitis (UC) and 36 with Crohn's disease (CD), were recruited for the present study. Calprotectin was analysed in stool samples, and C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were assessed in blood samples. CRP and calprotectin levels, and the ESR were observed to be significantly higher in patients with CD and UC compared with those of the healthy control subjects (P<0.0001). Furthermore, in patients with IBD and IBS, significant increases in faecal calprotectin and CRP levels were observed (694.8±685.0 µg/g in IBD vs. 85.8±136.1 µg/g in IBS and 0.851±1.200 mg/dl in IBD vs. 0.16±0.23 mg/dl in IBS, respectively; P<0.0001). Area under the receiver operating characteristic curve analysis revealed that, in patients with IBD, the levels of faecal calprotectin [0.931±0.029; 95% confidence interval (CI), 0.874­0.987] were significantly higher than that of CRP (0.865±0.041; 95% CI, 0.785­0.946) and the ESR (0.869±0.042; 95% CI, 0.786­0.952). These findings indicate that faecal calprotectin may represent a novel biomarker for diagnosing IBD and may be effective in distinguishing between IBD and IBS.


Assuntos
Fezes/química , Doenças Inflamatórias Intestinais/diagnóstico , Síndrome do Intestino Irritável/diagnóstico , Complexo Antígeno L1 Leucocitário/análise , Área Sob a Curva , Biomarcadores/análise , Sedimentação Sanguínea , Proteína C-Reativa/análise , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/metabolismo , Doença de Crohn/diagnóstico , Doença de Crohn/metabolismo , Humanos , Doenças Inflamatórias Intestinais/metabolismo , Síndrome do Intestino Irritável/metabolismo , Curva ROC
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