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1.
BMC Cancer ; 22(1): 809, 2022 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-35869490

RESUMO

BACKGROUND: Lung cancer is the leading cause of malignancy-related mortality and lung adenocarcinoma accounts for about 40% of lung malignancies. The aim of this study was to investigate the associations of intraflagellar transport protein 20 (IFT20) and Golgi matrix protein 130 (GM130) expression with clinicopathological features and survival in patients with lung adenocarcinoma. METHODS: The expressions of IFT20 and GM130 protein in cancerous and matched adjacent lung tissues of 235 patients with lung adenocarcinoma were assessed by tissue microarray and immunohistochemistry, which were indicated by the mean optical density (IOD/area), the rate of positive staining cells and staining intensity score. The correlation between IFT20 and GM130 protein was assessed by Spearman's rank correlation. Associations of IFT20 and GM130 protein expression with clinicopathological features of patients were analyzed by multivariate logistic regression models. The survival analysis of patients was performed by Cox proportional hazard regression models. RESULTS: With adjustment for multiple potential confounders, each one-point increase in IFT20 protein staining intensity score was significantly associated with 32% and 29% reduced risk for TNM stage in II ~ IV and lymphatic metastasis of patients, respectively (P < 0.05). And each one-point increase in GM130 protein staining intensity score was associated with a significant reduction in the risk of poor differentiation and tumors size > 7 cm by 29% and 38% for lung adenocarcinoma patients, respectively (P < 0.05). In stratified Cox model analysis, enhanced IFT20 staining intensity score was significantly decreased the risk of death by 16% for patients without distant metastasis. And elevated the IOD/area of GM130 expression significantly decreased the death risk of lung adenocarcinoma patients with tumor size > 7 cm or distant metastasis by 54% and 65%, respectively (P < 0.05). CONCLUSION: IFT20 and GM130 protein expressions were negatively associated with tumor differentiated types, size, TNM stage and lymphatic metastasis of lung adenocarcinoma. Both IFT20 and GM130 proteins have some protective effects on the survival of lung adenocarcinoma patients with specific clinicopathological features.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Autoantígenos/metabolismo , Neoplasias Pulmonares , Proteínas de Membrana/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais/metabolismo , Proteínas de Transporte , Humanos , Neoplasias Pulmonares/patologia , Metástase Linfática , Estadiamento de Neoplasias , Prognóstico
2.
Environ Sci Technol ; 56(18): 13439-13448, 2022 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-36069735

RESUMO

The rapid proliferation of planktonic algae induced by eutrophication and climate warming make algae dissolved organic matter (AOM) an important source of dissolved organic matter (DOM) in surface waters, but the understanding of the link between AOM composition and photo-reactivity/photo-transformation of DOM in aquatic systems is limited. Here, intracellular organic matter (IOM) from Microcystis aeruginosa was extracted and subjected to molecular weight (MW) fractionation. Results indicated that IOM had lower aromaticity and higher photosensitive activity compared to Suwannee River fulvic acid (SRFA). The photosensitive activity of IOM relied on both its molecular weight distribution and fluorescence components. The IOM fraction with the highest MW proteins had the lowest quantum yields of reactive intermediates (ΦRIs), which increased with the decrease of MW, while the fractions with more low-excitation tyrosine-like components had relatively higher ΦRIs. Parallel factor analysis and high-resolution mass spectrometry revealed that light radiation of IOM resulted in the composition transformation from tryptophan-like and tyrosine-like components to humic-like components, forming less aromatic and more saturated recalcitrant dissolved organic carbon. Our findings provide new insights into the photo-reactivity and photo-transformation of algae-derived organic matters and help to predict DOM formation involved in carbon cycling in water environment.


Assuntos
Matéria Orgânica Dissolvida , Triptofano , Carbono , Substâncias Húmicas/análise , Espectrometria de Massas , Plantas , Espectrometria de Fluorescência/métodos , Tirosina , Água
3.
Nanomedicine ; 39: 102460, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34530164

RESUMO

Transport ions into cells through nanocarrier to achieve ion-interference therapy provides new inspiration for cancer treatment. In this work, a pH-targeted and NIR-responsive NaCl-nanocarrier is prepared using surfactant Vitamin E-O(EG2-Glu) and modified with polydopamine (PDA) and pH-sensitive zwitterionic chitosan (ZWC). The NaCl-nanocarrier is decorated with NH4HCO3 and IR-780 to introduce near-infrared (NIR)-responsive performance and imaging. Once the NaCl-nanocarrier is exposed to NIR laser, the temperature rises rapidly because of the excellent photothermal conversion ability of PDA, then NH4HCO3 is decomposed into NH3 and CO2, which burst the nanocarrier, resulting in Cl- and Na+ "bomb-like" release. This pH-targeted nanocarrier accumulates more at tumor site and when irradiating the site with NIR light, the temperature rises and excessive Cl- and Na+ are released to destroy the ion homeostasis and inhibit tumor growth effectively. Through this strategy, the unique combination of ion interference therapy and photothermal therapy is achieved.


Assuntos
Nanopartículas , Fototerapia , Linhagem Celular Tumoral , Doxorrubicina , Concentração de Íons de Hidrogênio , Íons , Fototerapia/métodos , Terapia Fototérmica , Cloreto de Sódio
4.
Int J Mol Sci ; 23(12)2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35743060

RESUMO

The operation of mechanical equipment inevitably generates vibrations and noise, which are harmful to not only the human body but also to the equipment in use. Damping materials, which can convert mechanical energy into thermal energy, possess excellent damping properties in the glass transition region and can alleviate the problems caused by vibration and noise. However, these materials mainly rely on petroleum-based resources, and their glass transition temperatures (Tg) are lower than room temperature. Therefore, bio-based materials with high damping properties at room temperature must be designed for sustainable development. Herein, we demonstrate the fabrication of bio-based millable polyurethane (BMPU)/hindered phenol composites that could overcome the challenges of sustainable development and exhibit high damping properties at room temperature. BMPUs with a high Tg were prepared from modified poly (lactic acid)-based polyols, the unsaturated chain extender trimethylolpropane diallylether, and 4,4'-diphenylmethane diisocyanate, and 3,9-Bis-{1,1-dimethyl-2[ß-(3-tert-butyl-4-hydroxy-5-methylphenyl-)propionyloxy]ethyl}-2,4,8,10-tetraoxaspiro [5,5]-undecane (AO-80) was added to prepare BMPU/AO-80 composites. Finally, the properties of the BMPUs and BMPU/AO-80 composites were systematically evaluated. After adding 30 phr of AO-80, the Tg and maximum loss factor (tan δmax) of BMPU/AO-80 composites increased from 7.8 °C to 13.5 °C and from 1.4 to 2.0, respectively. The tan δmax showed an improvement of 43%. Compared with other polyurethanes, the prepared BMPU/AO-80 composites exhibited higher damping properties at room temperature. This study proposes a new strategy to reduce society's current dependence on fossil resources and design materials featuring high damping properties from sustainable raw materials.


Assuntos
Poliuretanos , Temperatura
5.
Zhonghua Nan Ke Xue ; 28(9): 779-785, 2022 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-37839002

RESUMO

OBJECTIVE: To study the impact of cadmium (Cd) on the expressions of PIWI-interacting RNAs (piRNA) in the rat testis and its possible action mechanism. METHODS: Twelve 6-week-old SD rats were randomly divided into a Cd-exposure and a control group, the former gavaged with CdCl2 at 3 mg/kg/d and the latter with normal saline, all for 28 successive days. Then the testicular tissues were collected from the rats, sperm concentration and motility were obtained by computer-assisted sperm analysis (CASA), and piRNA sequencing was performed using the gene chip, followed by bioinformatics analysis of differentially expressed piRNAs. RESULTS: Compared with the controls, the rats in the Cd-exposure group showed significantly decreased sperm concentration and motility (P < 0.05). The expressions of 272 piRNAs were up-regulated and 402 down-regulated after 28 days of Cd exposure, and 4 of the up-regulated piRNAs were consistent with the results of gene chip verification. Bioinformatics analysis showed that the 4 up-regulated piRNA target genes were involved in 50 biological processes, such as negative regulation of apoptosis, positive regulation of gene expression and positive regulation of GTPase activity, and mainly concentrated in 13 signaling pathways including transcription dysregulation, calcium and mitogen-activated protein kinase signaling pathways in cancer. Among them, PIRNA-DQ765261 had a binding site with Bcl-2. CONCLUSION: Cadmium can induce changes in the expressions piRNAs in the rat testicular tissue, and some piRNAs may be involved in the autophagy and apoptosis of sperm. Bcl-2 may be the target of PIRNA-DQ765261.


Assuntos
RNA de Interação com Piwi , Testículo , Masculino , Ratos , Animais , RNA Interferente Pequeno/genética , Testículo/metabolismo , Cádmio/toxicidade , Ratos Sprague-Dawley , Sêmen/química , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
6.
Anal Bioanal Chem ; 413(15): 3925-3932, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33932155

RESUMO

Acid phosphatase has become a significant indicator of prognostic and medical diagnosis, and its dysfunction may lead to a series of diseases. A novel dual-signal fluorescence method for acid phosphatase detection based on europium polymer (europium-pyridine dicarboxylicacid-adenine) and pyridoxal phosphate (PLP) was proposed. PLP coordinated with europium polymer via Eu3+ and P-O bonds, and the fluorescence of europium polymer was quenched due to the photoinduced electron transfer (PET) effect between aldehyde and europium polymer. Upon addition of acid phosphatase, the PLP was transformed to phosphate (Pi) and pyridoxal (PL). The PL was released from the surface of europium polymer, and the blue emission was enhanced due to the formation of internal hemiacetal, while the fluorescence of europium polymer recovered. The blue (PL) and red emission (Eu3+) were positively correlated with acid phosphatase activity; thus the sensitive assay of acid phosphatase was effectively achieved. The two signals were applied to determine the acid phosphatase with limits of detection (LOD) of 0.04 mU/mL and 0.38 mU/mL, and the linear ranges were 0.13-5.00 mU/mL and 1.25-20.00 mU/mL, respectively. The probe can be used to trace the acid phosphatase in biological systems and holds promise for use in clinical diagnosis and early prevention.


Assuntos
Fosfatase Ácida/análise , Corantes Fluorescentes/química , Limite de Detecção , Espectrometria de Fluorescência/métodos
7.
Toxicol Ind Health ; 37(8): 469-480, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34128436

RESUMO

Cadmium (Cd) is a heavy metal that is widely present in modern industrial production. It is a known, highly toxic environmental endocrine disruptor. Long-term exposure to Cd can cause varying degrees of damage to the liver, kidney, and reproductive system of organisms, especially the male reproductive system. This study aimed to explore the mechanism of Cd toxicity in the male reproductive system during puberty. Eighteen healthy 6-week-old male Sprague-Dawley rats were randomly divided into three groups (control group, low-dose group, and high-dose group) according to their body weight, with six in each group. Cd (0, 1, and 3 mg/kg/day) was given by gavage for 28 consecutive days. The results showed that Cd exposure to each dose group caused a decrease in the testicular organ coefficient and sperm count, compared with the control group. Cd exposure resulted in significant changes in testicular morphology in the 3 mg/kg/day Cd group. In the 1 and 3 mg/kg/day Cd groups, serum testosterone decreased and apoptosis of testicular cells increased significantly (p < 0.05). In addition, compared with the control group, the activity of glutathione peroxidase and superoxide dismutase in each Cd exposure dose group decreased, but the content of malondialdehyde in the high-dose, 3 mg/kg/day Cd treatment group significantly increased (p < 0.05). Although Cd exposure caused an increase in the messenger RNA (mRNA) levels of Bcl-2, Caspase-3 and Caspase-9 in the testicular tissues (p < 0.05), Bcl-2 expression was unchanged (p > 0.05). The expression level of Akt mRNA in testicular tissue of rats in the high-dose 3 mg/kg/day Cd group was increased (p < 0.05). Our data suggest that Cd affected testosterone levels, and apoptosis was observed in spermatids.


Assuntos
Cádmio/toxicidade , Reprodução/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testosterona/toxicidade , Animais , Apoptose/efeitos dos fármacos , Caspases/análise , Caspases/metabolismo , Genes bcl-2/efeitos dos fármacos , Masculino , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Testosterona/sangue
8.
Toxicol Appl Pharmacol ; 404: 115151, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32710958

RESUMO

Di (2-ethylhexyl) phthalate (DEHP) is a known environmental endocrine disruptor that impairs development of testis and spermatogenesis. This study aims to explore the effects of STAT3/p53 and PI3K-Akt-mTOR signaling pathway on DEHP-induced reproductive toxicity in pubertal male rat. 24 6-week-old male Sprague-Dawley rats were randomly divided into 4 groups (Control, low-dose, middle-dose and high-dose group) and were treated with increasing concentration of DEHP (0, 250, 500, 1000 mg/kg/day) respectively for 28 consecutive days by intragastric administration. Our results showed that DEHP exposure induced obvious morphological changes of testis, decreased organ coefficient of testis and sperm count, and increased testicular cell apoptosis in the 500 and 1000 mg/kg/day DEHP groups (p < .05). The serum testosterone decreased in a dose-dependent manner after treatment with DEHP. Furthermore, the exposure of DEHP elevated the levels of oxidative stress accompanied by upregulated expression of p53 and reduced expression of STAT3. In addition, compared with the control group, the expression of PI3K, p-Akt and p-mTOR proteins significantly decreased, whereas the downstream autophagy-related proteins phosphorylated ULK1, Beclin-1, Atg7, LC3-II obviously increased in the 250 mg/kg/day DEHP group (p < .05). The expression of p62 was reduced in DEHP-treated groups. Our data indicated that autophagy could be activated to protect testes from DEHP-induced reproductive damage by inhibiting PI3K-Akt-mTOR signaling pathway in the 250 mg/kg/day DEHP group. STAT3/p53-mediated mitochondrial apoptosis pathway might play a major role to cause testis injury and reproductive dysfunction in the 500 and 1000 mg/kg/day DEHP groups.


Assuntos
Dietilexilftalato/toxicidade , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Transcrição STAT3/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Dietilexilftalato/administração & dosagem , Relação Dose-Resposta a Droga , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Masculino , Malondialdeído/metabolismo , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Ratos Sprague-Dawley , Fator de Transcrição STAT3/genética , Maturidade Sexual , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Serina-Treonina Quinases TOR/genética , Testículo/efeitos dos fármacos , Proteína Supressora de Tumor p53/genética
9.
Exp Lung Res ; 46(7): 217-225, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32372722

RESUMO

Purpose: Impaired mucociliary clearance is an initial characteristic of recurrent cough, respiratory infection and chronic respiratory diseases. It has been demonstrated that prolonged inhalation of respirable silica particles results in a variety of pulmonary diseases, but whether the mucociliary system is involved in this process is unclear. This study aims to evaluate the effects of silica particles on mucociliary structure and MUC5B production in respiratory tract.Materials and Methods: C57BL/6 mice were administered with 2.5 mg silica particles through a single intratracheal instillation. The changes of mucociliary structure and MUC5B expression in trachea was evaluated by HE and AB-PAS staining, transmission electron microscopy and immunohistochemistry on days 1, 7, 28 and 84 post-exposure.Results: The mucociliary structure of airway epithelium was obviously impaired by silica particles, showing disordered, shortened or partially lost cilia on the surface, increased mucus in mucous layer and submucosal glands from day 7 to day 84. A variety of ultrastructural abnormalities were discovered in silica-exposed airway cilia, including absence of central pair microtubules, disorganized microtubules and clusters of axoneme on day 1 and 7. The numbers of ciliary axonemes and basal bodies in ciliated epithelial cells were significantly decreased, whereas the proportion of abnormal axonemes was gradually increased with exposure to silica particles (P < 0.05). In addition, silica particles significantly decreased MUC5B expression on the surface of airway epithelium on day 28 and 84, but obviously increased its production in submucosal glands from day 1 to day 84 (P < 0.01).Conclusions: Silica particles could lead to ultrastructural defects in airway cilia, mucus hypersecretion and altered MUC5B expression in trachea, indicating that impaired mucociliary structure and altered MUC5B production might participate in the development of silica-related respiratory diseases.


Assuntos
Cílios/efeitos dos fármacos , Cílios/metabolismo , Pneumopatias/metabolismo , Mucina-5B/metabolismo , Muco/enzimologia , Muco/metabolismo , Dióxido de Silício/farmacologia , Animais , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Depuração Mucociliar/efeitos dos fármacos , Traqueia/efeitos dos fármacos , Traqueia/metabolismo
10.
Toxicol Ind Health ; 36(10): 759-768, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32783763

RESUMO

Long-term inhalation of carbon black nanoparticles (CBNPs) leads to pulmonary inflammatory diseases. Histone deacetylase 6 (HDAC6) has been identified as an important regulator in the development of inflammatory disorders. However, the direct involvement of HDAC6 in CBNPs-induced pulmonary inflammatory responses remains unclear. To explore whether HDAC6 participates in CBNPs-induced pulmonary inflammation, human bronchial epithelial cell line (16HBE cells) was transfected with HDAC6 small interference RNA (siRNA) and then exposed to CBNPs at concentrations of 0, 25, and 50 µg/ml for 24 h. Intracellular HDAC6 and intraflagellar transport protein 88 (IFT88) mRNA and protein were determined by real-time polymerase chain reaction and Western blot, respectively. The secretions of inflammatory cytokines including interleukin (IL)-8, tumor necrosis factor (TNF)-α, IL-6, and IL-1ß were measured by enzyme-linked immunosorbent assay. CBNPs induced a significant increase in the expressions of IL-8 and IL-6, accompanied by a high level of intracellular HDAC6 mRNA when compared with a blank control group (p < 0.05). However, there were no significant changes in the levels of TNF-α secretion, intracellular HDAC6 and IFT88 protein induced by CBNPs (p > 0.05). The HDAC6 mRNA expression was significantly suppressed in HDAC6 siRNA-transfected cells (p < 0.05). The secretions of IL-8, TNF-α, and IL-6 were significantly less in HDAC6 siRNA-transfected cells than that in normal 16HBE cells with exposure to 25 or 50 µg/ml of CBNPs, but intracellular IFT88 mRNA expression was markedly increased in HDAC6 siRNA-transfected cells when compared with normal 16HBE cells exposed to 50 µg/ml of CBNPs (all p < 0.05). Downregulation of the HDAC6 gene inhibits CBNPs-induced inflammatory responses in bronchial epithelial cells, partially through regulating IFT88 expression. It is suggested that CBNPs may trigger inflammatory responses in bronchial epithelial cells by an HDAC6/IFT88-dependent pathway.


Assuntos
Desacetilase 6 de Histona/metabolismo , Nanopartículas/efeitos adversos , Pneumonia/induzido quimicamente , Pneumonia/genética , RNA Mensageiro/metabolismo , Fuligem/efeitos adversos , Fuligem/metabolismo , Adulto , Broncopatias/fisiopatologia , Resistência à Doença/genética , Resistência à Doença/fisiologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Feminino , Desacetilase 6 de Histona/genética , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/induzido quimicamente , Doenças Profissionais/genética , Doenças Profissionais/fisiopatologia , Exposição Ocupacional/efeitos adversos , Pneumonia/fisiopatologia
11.
Lung ; 197(6): 783-791, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31520180

RESUMO

BACKGROUND: Prolonged exposure to crystalline silica leads to persistent pulmonary inflammation and progressive fibrosis. Connective tissue growth factor (CTGF) has emerged as a potent proinflammatory and profibrotic regulator to participate in a variety of chronic inflammatory diseases. However, the role of CTGF in silica-induced pulmonary inflammation remains poorly understood. METHODS: To explore the effect of CTGF on inflammatory responses caused by silica particles, human bronchial epithelial cells (16HBE) were transfected with CTGF siRNA and exposed to silica particles at concentrations of 0, 12.5, 25, 50, 100 µg/ml for 48 h. Intracellular CTGF mRNA and protein expressions were determined by RT-PCR and Western blotting, respectively. The levels of inflammatory cytokines including IL-8, TNF-α, IL-6, IL-1ß, IL-17A and TGF-ß1 were measured by ELISA kits. RESULTS: Silica particles induce significantly elevated intracellular CTGF mRNA expression in 16HBE cells in a dose-dependent manner when compared with blank control group (P < 0.05). The secretions of IL-8, TNF-α, IL-6 and IL-17A were also significantly increased by silica particles (P < 0.05). After exposure to 25 or 50 µg/ml silica particles, the expression of intracellular CTGF mRNA was significantly inhibited in 16HBE cells when transfected with CTGF siRNA (P < 0.05). The secreted levels of IL-8, TNF-α, IL-6 and IL-17A induced by silica particles were also significantly lower from CTGF siRNA-transfected cells than that from normal 16HBE cells (P < 0.05). CONCLUSION: Inhibition of CTGF gene attenuates silica-induced inflammatory responses in bronchial epithelial cells, suggesting that CTGF could be a pivotal regulator in the development of silica-induced inflammation.


Assuntos
Fator de Crescimento do Tecido Conjuntivo/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Inflamação/metabolismo , Dióxido de Silício/farmacologia , Western Blotting , Brônquios/citologia , Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Ensaio de Imunoadsorção Enzimática , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Técnicas de Silenciamento de Genes , Humanos , Inflamação/imunologia , Interleucina-17/imunologia , Interleucina-1beta/efeitos dos fármacos , Interleucina-1beta/imunologia , Interleucina-6/imunologia , Interleucina-8/efeitos dos fármacos , Interleucina-8/imunologia , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Mucosa Respiratória/citologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Crescimento Transformador beta1/efeitos dos fármacos , Fator de Crescimento Transformador beta1/imunologia , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/imunologia
12.
Toxicol Ind Health ; 35(3): 228-238, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30755103

RESUMO

Di(2-ethylhexyl)phthalate (DEHP) is a typical endocrine-disrupting chemical and reproductive toxicant. Although previous studies have attempted to describe the mechanism by which DEHP exposure results in reproductive dysfunction, few studies focused on puberty, a critical period of reproductive development, and the increased susceptibility to injury in adolescents. To elucidate the mechanism underpinning the testicular effects of DEHP in puberty, we sought to investigate the JAZF1/TR4 pathway in the testes of pubertal rats. Specifically, we focused on the role of the JAZF1/TR4 pathway in male reproduction, including the genes JAZF1, TR4, Sperm 1, and Cyclin A1. In the present study, rats were exposed to increasing concentrations of DEHP (0, 250, 500, and 1000 mg/kg/day) by oral gavages for 30 days. Then we assayed testicular zinc and oxidative stress levels. Our results indicated that DEHP exposure could lead to oxidative stress and decrease the contents of testicular zinc. Additionally, significant morphological changes and cell apoptosis were observed in testes exposed to DEHP, as identified by hematoxylin and eosin staining and the terminal deoxynucleotidyl transferase-mediated nick and labeling assay. By measuring the expression levels of the above relevant genes by qPCR, we found the DEHP-induced increased expression of JAZF1 and decreased expression of TR4, Sperm 1, and Cyclin A1. Therefore, we have demonstrated that in vivo exposure to DEHP might induce reproductive toxicity in pubertal male rats through the JAZF1/TR4 pathway and oxidative stress.


Assuntos
Dietilexilftalato/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Plastificantes/toxicidade , Maturidade Sexual/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Ciclina A1/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Células Germinativas/efeitos dos fármacos , Masculino , Fatores do Domínio POU/efeitos dos fármacos , Fatores do Domínio POU/genética , Ratos , Ratos Sprague-Dawley , Receptores de Esteroides/efeitos dos fármacos , Receptores de Esteroides/genética , Receptores dos Hormônios Tireóideos/efeitos dos fármacos , Receptores dos Hormônios Tireóideos/genética , Reprodução/efeitos dos fármacos , Testículo/patologia
13.
Environ Toxicol ; 32(3): 1055-1064, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27416487

RESUMO

Di(2-ethylhexyl) phthalate (DEHP), a plasticizer of synthetic polymers, is a well-known endocrine disrupting chemical (EDC) and reproductive toxicant. Addressing the unclear mechanism of DEHP-induced reproductive dysfunction, this study used GC-2spd cells to investigate the molecular mechanism involved in the DEHP-induced toxicity in the male reproductive system. The results indicated that the apoptotic cell death was significantly induced by DEHP exposure over 100 µM. Furthermore, DEHP treatment could induce oxidative stress in GC-2spd cells involving in the decrease of superoxide dismutase (SOD) activity (200 µM) and glutathione peroxidase (GSH-Px) activity (50 and 100 µM). In addition, DEHP induction also caused the elevated ratios of Bax/Bcl-2, release of cytochrome c and decomposition of procaspase-3 and procaspase-9 in GC-2spd cells. Taken together, our work provided the evidence that DEHP exposure might induce apoptosis of GC-2spd cells via mitochondria pathway mediated by oxidative stress. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1055-1064, 2017.


Assuntos
Apoptose/efeitos dos fármacos , Dietilexilftalato/toxicidade , Disruptores Endócrinos/toxicidade , Mitocôndrias/efeitos dos fármacos , Espermatócitos/efeitos dos fármacos , Animais , Caspase 3/metabolismo , Caspase 9/metabolismo , Células Cultivadas , Masculino , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Plastificantes/toxicidade , Transdução de Sinais/efeitos dos fármacos , Espermatócitos/metabolismo
14.
Reprod Toxicol ; 125: 108554, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38331007

RESUMO

Cadmium (Cd) is a harmful environmental pollutant that disrupts public health, including respiratory, digestive, and reproductive systems. In this study, male rats were exposed to CdCl2 at a dose of 3 mg/kg by oral for 28 days to investigate the impact on spermatogenesis. Testis tissue samples were collected after sacrifice, and piRNA expression levels were measured using piRNA microarray and qPCR. PiRNAs, specialized molecules involved in spermatogenesis, were examined. CdCl2 exposure led to disrupted piRNA expression, particularly in piRNA-DQ759395 in rats. This piRNA was found to have a binding site with p53, and a similar piRNA-DQ717867 was discovered in mice. In GC-2spd cells, CdCl2 exposure increased piRNA-DQ717867 expression, which resulted in cell cycle arrest and abnormal expression of cell cycle-related proteins. The activation of p53-related pathways and disruptions in cell cycle regulation were also observed. Antagomir-717867 transfections and PFT-a pretreatment in GC-2spd cells supported the involvement of piRNA-DQ717867 in regulating cell cycle-related proteins. This study suggests that Cd exposure induces abnormal expression of piRNA-DQ759395 in rat testis and that piRNA-DQ717867 may regulate p53, causing cell cycle abnormalities in GC-2spd cells. These findings help understand the mechanisms of male reproductive toxicity caused by Cd exposure and emphasize the role of piRNAs in cell cycle regulation and male reproductive health.


Assuntos
Cádmio , RNA de Interação com Piwi , Masculino , Ratos , Camundongos , Animais , Cádmio/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Espermatogênese , Testículo/metabolismo
15.
Zhonghua Nan Ke Xue ; 19(5): 387-91, 2013 May.
Artigo em Chinês | MEDLINE | ID: mdl-23757957

RESUMO

OBJECTIVE: To construct a mammalian expression plasmid of the BC022687 gene and investigate the expression and localization of the fusion protein in Chinese hamster ovary (CHO) cells. METHODS: The BC022687 coding sequence was amplified by polymerase chain reaction (PCR) and subcloned into the pEGFP-C1 vector carrying the gene of green fluorescence protein (GFP). After the target region was sequenced, the recombinant plasmid was transfected into CHO cells, and its expression in the CHO cells was determined by Western blot. The localization of GFP-tagged BC022687 in the CHO cells was observed by laser scanning confocal microscopy. RESULTS: BC022687 was successfully cloned into the mammalian expression vector pEGFP-C1, with the restriction fragment length of 950 bp. The expression of the fusion protein was confirmed, with the relative molecular weight of 64 000. The GFP-tagged BC022687 protein was mainly localized in the cytoplasm, and also presented in the centrioles in the transfected CHO cells. CONCLUSION: The successful construction of the plasmid expressing BC022687 in CHO cells has laid a foundation for further studies on the role of this protein in ciliogenesis.


Assuntos
Centrossomo/metabolismo , Cílios/metabolismo , Plasmídeos , Proteínas Recombinantes de Fusão/genética , Animais , Células CHO , Cricetinae , Cricetulus , DNA Complementar , Vetores Genéticos , Masculino , Camundongos , Transfecção
16.
Materials (Basel) ; 16(2)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36676509

RESUMO

As a wide bandgap semiconductor material, silicon carbide has promising prospects for application. However, its commercial production size is currently 6 inches, and the difficulty in preparing larger single crystals increases exponentially with size increasing. Large-size single crystal growth is faced with the enormous problem of radial growth conditions deteriorating. Based on simulation tools, the physical field of 8-inch crystal growth is modeled and studied. By introducing the design of the seed cavity, the radial temperature difference in the seed crystal surface is reduced by 88% from 93 K of a basic scheme to 11 K, and the thermal field conditions with uniform radial temperature and moderate temperature gradient are obtained. Meanwhile, the effects of different processing conditions and relative positions of key structures on the surface temperature and axial temperature gradients of the seed crystals are analyzed in terms of new thermal field design, including induction power, frequency, diameter and height of coils, the distance between raw materials and the seed crystal. Meanwhiles, better process conditions and relative positions under experimental conditions are obtained. Based on the optimized conditions, the thermal field verification under seedless conditions is carried out, discovering that the single crystal deposition rate is 90% of that of polycrystalline deposition under the experimental conditions. Meanwhile, an 8-inch polycrystalline with 9.6 mm uniform deposition was successfully obtained after 120 h crystal growth, whose convexity is reduced from 13 mm to 6.4 mm compared with the original scheme. The results indicate that the optimized conditions can be used for single-crystal growth.

17.
Food Chem Toxicol ; 173: 113649, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36736878

RESUMO

Perfluorooctanoic acid (PFOA), a man-made chemical widely used in consumers, could cause male reproductive toxicity by disrupting blood-testis barrier (BTB) integrity. Autophagy in Sertoli cells is essential for regulation of spermatogenesis and BTB. However, it remains a mystery that whether PFOA-induced BTB injury is associated with autophagy in Sertoli cells. In this study, we found that PFOA dose-dependently disrupted tight junction (TJ) function in Sertoli cells in vivo and in vitro. Furthermore, the results from transmission electron microscopy, Western blot and immunofluorescence analysis revealed that PFOA induced the accumulation of autophagosome in testicular Sertoli cells as well as TM4 cells. Further study confirmed that autophagosome accumulation resulted from the blockage of autophagic degradation because of disruption of autophagosome and lysosome fusion via downregulation of the expression of α-SNAP. In parallel, the overexpressed MMP9 was also observed in vivo and in vitro. Conversely, overexpression of α-SNAP inhibited the expression of MMP9 in TM4 cells. In conclusion, PFOA blocks autophagic flux through downregulating the expression levels of α-SNAP in Sertoli cells, and then induces the accumulation of MMP9 leading to disruption of TJ function. This finding will provide clues for effective prevention and treatment of PFOA-induced male reproductive toxicity.


Assuntos
Metaloproteinase 9 da Matriz , Células de Sertoli , Humanos , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Junções Íntimas , Proteínas de Ligação a Fator Solúvel Sensível a N-Etilmaleimida/metabolismo , Proteínas de Ligação a Fator Solúvel Sensível a N-Etilmaleimida/farmacologia , Testículo , Espermatogênese , Autofagia , Barreira Hematotesticular
18.
ACS Omega ; 6(44): 30003-30011, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34778671

RESUMO

Petroleum-based polymer materials heavily rely on nonrenewable petrochemical resources, and damping materials are an important category of them. As far as green chemistry, recycling, and damping materials are concerned, there is an urgent need for renewable and recyclable biobased materials with high damping performance. Thus, this study designs and synthesizes a series of polylactic acid-based thermoplastic polyurethanes (PLA-based TPUs) composed of modified polylactic acid polyols, 4,4'-diphenylmethane diisocyanate, and 1,4-butanediol. PLA-based TPUs, as prepared, display excellent mechanical properties, damping performance, and biocompatibility. Otherwise, they can be used for three-dimensional printing (3D printing). Under multiple recycling, the overall performance of PLA-based TPUs is still maintained well. Overall, PLA-based TPUs, as designed in this article, show a potential application in damping materials under room temperature and personalized shoes via 3D printing and could realize resource recycling and material reuse.

19.
Talanta ; 228: 122189, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33773709

RESUMO

Hexosaminidases (Hexs) as an exoglycosidase participates in the catalytic hydrolysis of non-reducing end of glycoconjugates in the biological system. The fluctuation of Hexs level could cause many hereditary neurodegenerative diseases such as Tay-Sachs and Sandhoff. The Hexs activity is significantly up-regulated in colorectal cancer and kidney injury tissue so that it is particularly important to construct a fluorescent probe with significant signal change to understand its physiological role. In this work, DyOH was selected as fluorophore scaffolds to synthesize probe Hex-1 for detection of Hexs with good water solubility, high specificity, large stokes shift and quick response. Hex-1 can sensitively detect Hexs with the low detection limit (0.025 mU mL-1) in vitro by "naked eye" due to superior spectral properties of DyOH. Furthermore, Hex-1 was not only employed for imaging Hexs in living cells with low toxicity, but also successfully applied to evaluate the fluctuation of Hexs activity during drug induced kindey injury in living HK-2 cells. These results indicated that Hex-1 could be used as a potential image tool to further explore the pathogenesis of kidney disease and cancer.


Assuntos
Nefropatias , Preparações Farmacêuticas , Corantes Fluorescentes , Hexosaminidases , Humanos , Rim
20.
Talanta ; 218: 121100, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32797867

RESUMO

Telomerase and microRNA (miRNA) are biomarkers closely related to tumors. Simultaneous detection of both markers can improve accuracy and reliability of early diagnosis. Based on the mechanism of fluorescence resonance energy transfer (FRET), two fluorescent DNA probes were designed for telomerase and miRNA-21. The probes were wrapped by gelatin through electrostatic interaction to form nanoparticles. After that, we synthesized molecularly imprinted coating of transferrin on the surface of gelatin nanoparticles, which can avoid the immune stress response and macrophage phagocytosis to help gelatin nanoparticles enter into the cells smoothly through endocytosis. Following with the degradation of gelatin in the cells, DNA probes were released to react with telomerase and miRNA-21 and lead to the change of the fluorescence signal. Thereby the simultaneous imaging of telomerase and miRNA-21 were successfully achieved in HeLa cells and HepG2 cells. The proposed strategy shows the simultaneous imaging for different biological markers with DNA probes by preventing them from being hydrolyzed with nucleases before the determination and achieves reliable method for early diagnosis of cancer.


Assuntos
MicroRNAs , Nanopartículas , Telomerase , Sondas de DNA , Gelatina , Células HeLa , Humanos , Reprodutibilidade dos Testes , Telomerase/metabolismo
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