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1.
Ecotoxicol Environ Saf ; 223: 112571, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34352584

RESUMO

The present study investigates whether paraquat (PQ) regulates polarization of alveolar macrophages through glycolysis and promotes the occurrence of acute lung injury in rats. In vivo, the PQ intraperitoneal injection was used to construct a model of acute lung injury in rats. In vitro, the study measured the effect of different concentrations of PQ on the viability of the alveolar macrophages, and explored the polarization and glycolysis metabolism of alveolar macrophages at different time points after PQ intervention. Compared with the normal control (NC) group, the lung pathological damage in rats increased gradually after PQ poisoning, reaching a significant degree at 48 h after poisoning. The PQ-poisoned rat serum showed increased expressions of interleukin-6 (IL-6), tumor necrosis factor- α (TNF-α), and M1 macrophage marker, iNOS, while the expression of interleukin-10 (IL-10) and M2 macrophage marker, Arg1, decreased. The toxic effect of PQ on alveolar macrophages was dose- and time-dependent. Compared with the NC group, IL-6 and TNF-α in the cell supernatant gradually increased after PQ intervention, while the IL-10 content gradually decreased. The PQ intervention in alveolar macrophages increased the expression of intracellular glycolysis rate-limiting enzyme pyruvate kinase isozymes M1/M2 (PKM1/M2), lactate, lactate/pyruvate ratio, and the polarization of alveolar macrophage towards M1. Inhibition of cellular glycolysis significantly reduced the PQ-induced alveolar macrophage polarization to M1 type. Thus, PQ induced increased polarization of lung macrophages toward M1 and decreased polarization toward M2, promoting acute lung injury. Therefore, it can be concluded that PQ regulates the polarization of alveolar macrophages through glycolysis.


Assuntos
Lesão Pulmonar Aguda , Paraquat , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Glicólise , Pulmão/metabolismo , Macrófagos Alveolares/metabolismo , Paraquat/toxicidade , Ratos , Fator de Necrose Tumoral alfa/metabolismo
2.
Front Public Health ; 9: 666460, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395359

RESUMO

Objective: The study aimed to examine the relationship between perceived stress and post-traumatic stress disorder (PTSD) among frontline medical staff during the lockdown in Wuhan city, China, due to the COVID-19 outbreak. Methods: The study was conducted in August 2020, which included 516 medical staff between 21 to 65 years. The PTSD Checklist-Civilian, Perceived Stress Scale, Insomnia Severity Index, and Compassion Fatigue Short Scale were used. Results: The results indicated that 10.5% of the medical staff experienced PTSD symptoms, and insomnia severity mediated the effect of perceived stress on PTSD. In addition, compassion fatigue moderated the association between perceived stress and PTSD. Conclusion: The study elucidated the mechanisms underlying the association between perceived stress and PTSD. Moreover, it emphasized the importance of long-term monitoring of the mental health status of frontline medical staff who supported Wuhan. The results can serve as reference for relevant medical and health departments to formulate active interventions and preventive measures against PTSD for unsung heroes who put their lives on the line during difficult times.


Assuntos
COVID-19 , Epidemias , Transtornos de Estresse Pós-Traumáticos , Controle de Doenças Transmissíveis , Humanos , Corpo Clínico , SARS-CoV-2 , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Estresse Psicológico/epidemiologia
3.
Clin Nurs Res ; : 10547738211030002, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34259087

RESUMO

This study explores the association between life satisfaction and depression among patients with cardiovascular diseases and whether this association is mediated by self-esteem. A cross-sectional study was conducted in a third-grade hospital. We examined 300 patients with cardiovascular diseases with a mean age of 62.00 years (females, 133). Life satisfaction was associated with depression. Adding self-esteem to the model weakened the strength of the association between the two. Moreover, 34.2% of the effect of life satisfaction on depression could be explained by self-esteem. We found that self-esteem could totally explain the effect of life satisfaction on depression among patients with cardiovascular diseases.

4.
Int J Clin Exp Pathol ; 8(8): 9032-41, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26464645

RESUMO

OBJECTIVE: This study aimed to investigate the radiosensitivity of bortezomib to cervical cancer and the possible underlying mechanism. METHODS: HeLa and SiHa cell lines with or without hypoxia treatment were divided into control, radiation alone, bortezomib alone, and radiotherapy plus bortezomib groups. CCK8 assay, clone formation assay, flow cytometry, and immunofluorescence test were used to measure cell proliferation, colony formation, apoptosis, and DNA double-strand break (DSB). Western blot analysis was performed to detect the expression of HIF-1α, PARP-1, and caspase-3, -8, and -9. RESULT: Statistical analysis of data revealed that bortezomib at nanomolar level exerted a radiosensitization effect on both cervical cancer cell lines in normoxia or hypoxia. Western blot analysis showed that the drug could inhibit hypoxia-related HIF-1α expression to increase apoptosis-related caspase-3, -8, and -9 activation and DNA DSB-related PARP-1 cleavage. CONCLUSIONS: Radiotherapy sensitization of bortezomib on cervical cancer cell lines had a drug-dose relation, and sensitization in hypoxia was more remarkable than in normoxia. Bortezomib may be a potential radiotherapy sensitization drug for cervical cancer.


Assuntos
Bortezomib/farmacologia , Expressão Gênica/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Hipóxia/metabolismo , Radiossensibilizantes/farmacologia , Neoplasias do Colo do Útero/metabolismo , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Células HeLa , Humanos , Hipóxia/patologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/radioterapia
5.
Sci Rep ; 5: 9476, 2015 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-25820571

RESUMO

Radioresistance has been an important factor in restricting efficacy of radiotherapy for non-small cell lung cancer (NSCLC) patients and new approaches to inhibit cancer growth and sensitize irradiation were warranted. Despite the important role of ubiquitin/proteasome system (UPS) during cancer progression and treatment, the expression and biological role of ubiquitin (Ub) in human NSCLC has not been characterized. In this study, we found that ubiquitin was significantly overexpressed in 75 NSCLC tissues, compared to their respective benign tissues by immunohistochemistry (P < 0.0001). Knock-down of ubiquitin by mixed shRNAs targeting its coding genes ubiquitin B (UBB) and ubiquitin C (UBC) suppressed the growth and increased the radiosensitivity in NSCLC H1299 cells. Apoptosis and γ H2AX foci induced by X-ray irradiation were enhanced by knock-down of ubiquitin. Western blot and immunostaining showed that knock-down of ubiquitin decreased the expression and translocation of NF-κB to the nucleus by reduced phospho-IκBα after irradiation. Suppression of ubiquitin decreased the proliferation and radioresistance of H1299 transplanted xenografts in nude mice by promoting apoptosis. Taken together, our results demonstrate the critical role of ubiquitin in NSCLC proliferation and radiosensitivity. Targeting ubiquitin may serve as a potentially important and novel approach for NSCLC prevention and therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Proliferação de Células/genética , Ubiquitina/biossíntese , Animais , Apoptose/efeitos da radiação , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Camundongos , NF-kappa B/biossíntese , NF-kappa B/genética , Tolerância a Radiação/genética , Ubiquitina/genética , Raios X , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Chin J Cancer Res ; 26(5): 622-6, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25400429

RESUMO

Triptolide (TPL/TL) is a natural drug with novel anticancer effects. Preclinical studies indicated that TPL inhibits cell proliferation, induces cell apoptosis, inhibits tumor metastasis and enhances the effect of other therapeutic methods in various cancer cell lines. Multiple molecules and signaling pathways, such as caspases, heat-shock proteins, NF-κB, and deoxyribonucleic acid (DNA) repair-associated factors, are associated with the anti-cancer effect. TPL also improves chemoradiosensitivity in cancer therapy. Phase I trials indicate the potential clinical value of TPL use. However, further trials with larger sample sizes are needed to confirm these results.

7.
Int J Clin Exp Pathol ; 7(11): 7622-32, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25550798

RESUMO

Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, has been reported to have antitumor effects. In some tumor models, the combination of celecoxib with chemotherapy agents has shown synergistic antitumor effect; however, the effect of celecoxib combination with tegafur/gimeracil/oteracil potassium on the malignant biological behaviors of gastric cancer in nude mice is unclear. In this study, female nude mice were subcutaneously transplanted with SGC-7901 gastric cancer cells. When the tumor model formed, the mice were divided into control group, celecoxib group, tegafur/gimeracil/oteracil potassium group, and the combination of both drug regimens group. Mice were treated for 3 weeks. Following treatment, the proliferating index was calculated, apoptosis related proteins, COX-2, vascular endothelial growth factor-C (VEGF-C) and lymphatic vessel density were quantified in tumor tissues by immunohistochemistry. Apoptosis was evaluated by TUNEL staining. The results revealed that celecoxib and tegafur/gimeracil/oteracil potassium alone significantly inhibited tumor growth. The combination of these two drugs showed a synergistic antitumor effect. Both celecoxib and tegafur/gimeracil/oteracil potassium alone inhibited proliferation and promoted apoptosis. The combination of these two drugs further enhanced this anticancer effect. Both celecoxib and the combination treatment inhibited lymphangiogenesis and the expression of COX-2 and VEGF-C. However, tegafur/gimeracil/oteracil potassium treatment had no obvious effect on lymphangiogenesis. These results suggested that the combination of celecoxib and tegafur/gimeracil/oteracil potassium produced a synergistic antitumor effect, possibly by inhibiting the proliferation of tumor cells and promoting apoptosis. Celecoxib and celecoxib in combination with tegafur/gimeracil/oteracil potassium possibly by reducing the expression of COX-2, in turn down-regulating the expression of VEGF-C, resulted in the inhibition of lymphangiogenesis.


Assuntos
Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Pirazóis/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Estômago/efeitos dos fármacos , Sulfonamidas/uso terapêutico , Animais , Antineoplásicos/farmacologia , Celecoxib , Linhagem Celular Tumoral , Ciclo-Oxigenase 2/metabolismo , Quimioterapia Combinada , Feminino , Mucosa Gástrica/metabolismo , Humanos , Camundongos , Camundongos Nus , Pirazóis/farmacologia , Estômago/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Sulfonamidas/farmacologia , Fator C de Crescimento do Endotélio Vascular
8.
Int J Clin Exp Med ; 7(11): 4115-22, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25550921

RESUMO

OBJECTIVE: Lung cancer remains the leading cause of cancer-related death worldwide and microRNAs (miRNAs) play important roles in lung cancer progression. In this study, we investigate the effects of miR-132/212 cluster on the growth of subcutaneous xenografts of human lung cancer H1299 cells in nude mice, and further explore the underlying mechanisms. METHODS: Nude mice with subcutaneous transplantation tumor of human lung cancer H1299 cells were randomly divided into three groups: the sham group, the control vector group, and the microRNA-132/212 group. The control vector and microRNA-132/212 cluster plasmid was intratumoral injected respectively. Tumor volume was measured during the intervention process, with a tumor growth curve generated. Immunohistochemistry was performed to analyze the expression level of Ki-67, P21, CyclinD1 and CD31 in each group. RESULTS: The tumor volume of miR-132/212 group was significantly smaller than that of the control group at the terminal time point (P < 0.05). The expression levels of Ki-67, CyclinD1 and CD31 in the miR-132/212 group was significantly lower than the control group (P < 0.05), while the expression levels of P21 in the miR-132/212 group were significantly higher than the control group (P < 0.05). CONCLUSION: miR-132/212 cluster significantly inhibited the growth of subcutaneous xenografts of human lung cancer H1299 cells in nude mice. The inhibitory effect of miR-132/212 cluster in tumor growth may be mediated by upregulating the expression of P21 and downregulating the expression of CyclinD1, thereby inhibiting tumor tissue proliferation and angiogenesis and resulting in the inhibition of tumor growth.

9.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 29(5): 458-61, 2013 May.
Artigo em Chinês | MEDLINE | ID: mdl-23643260

RESUMO

OBJECTIVE: To investigate the anti-tumor effect of celecoxib combined with tegafur gimeracil oteracil potassium on subcutaneous xenograft tumor of gastric cancer in nude mice and analyze the possible mechanism. METHODS: A xenograft tumor model of gastric cancer was established subcutaneously in nude mice. After the largest diameter of tumor reached about 5 mm, the nude mice were randomly divided into 4 groups: the control group, the celecoxib group, the tegafur gimeracil oteracil potassium group, and the combination group; the drug was administered respectively for 21 days. Thereafter, tumor tissues were collected, tumor volume was measured, and tumor inhibition rate was calculated. Apoptosis was determined by TUNEL assay and the expression levels of PCNA, Bcl-2 and caspase-3 by immunohistochemistry. RESULTS: The tumor inhibition rates of the celecoxib group, the tegafur gimeracil oteracil potassium group, the combination group were 30.8%, 50.1%, 78.8%, respectively. The apoptosis index in treatment groups was higher than that in the control group (P<0.01), and the combination group was higher than single drug group (P<0.01). The expressions of PCNA, Bcl-2 in treatment groups were lower than those in the control group (P<0.01), and the combination group was lower than single drug group (P<0.05). The expression of caspase-3 in treatment groups was higher than that in the control group (P<0.05), and the combination group was higher than single drug group (P<0.01). CONCLUSION: Both celecoxib and tegafur gimeracil oteracil potassium showed obvious anti-tumor effect, and the combination of the two acted synergistically. The possible mechanism was that they inhibited tumor growth through inhibiting proliferation and promoting apoptosis of the tumor cells.


Assuntos
Antineoplásicos/administração & dosagem , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Pirazóis/administração & dosagem , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Sulfonamidas/administração & dosagem , Tegafur/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Celecoxib , Linhagem Celular Tumoral , Humanos , Camundongos , Camundongos Nus , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
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