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1.
Bull World Health Organ ; 102(4): 234-243, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38562205

RESUMO

Objective: To assess knowledge and practices related to snakebite prevention among Chinese residents. Methods: By using a multistage random sampling approach augmented by snowball sampling, we surveyed residents from 10 provinces, one municipality and one autonomous region south of the Yangtze River Basin between May 2022 and February 2023. We supplemented the data with a national online survey. We used a χ2-test to identify differences in knowledge and behaviour across various demographic characteristics. We conducted multifactor logistic regression analyses to evaluate factors potentially influencing snakebite knowledge and practices. Findings: We obtained 55 775 valid survey responses, 16 200 respondents from the face-to-face survey and 39 575 respondents from the online survey. Only 25.7% (14 325) respondents demonstrated adequate knowledge about snakebites whereas 25.6% (14 295) respondents knew basic first-aid practices or preventive behaviours. Age, marital status, educational attainment, occupation, type of residence and frequency of exposure to nature are significant independent variables affecting snakebite knowledge (P-values: < 0.05). On the other hand, gender, age, marital status, educational attainment, occupation and type of residence were significant independent variables affecting the behaviour of snakebite prevention and first aid (P-values: < 0.05). Conclusion: There is a notable shortfall in knowledge, first aid and preventive behaviours among Chinese residents regarding snakebites. Misguided first aid practices can severely compromise the effectiveness of evidence-based therapeutic interventions. Consequently, improving health education concerning snakes and snakebites in this population is needed.


Assuntos
Mordeduras de Serpentes , Animais , Humanos , Mordeduras de Serpentes/epidemiologia , Mordeduras de Serpentes/prevenção & controle , Estudos Transversais , Serpentes , China/epidemiologia , Inquéritos e Questionários , Conhecimentos, Atitudes e Prática em Saúde
2.
BMC Public Health ; 24(1): 1704, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926898

RESUMO

OBJECTIVE: To analyze the vulnerability factors of snakebite patients in China. METHODS: Multi-stage random sampling was used as the main sampling method and snowball sampling as the auxiliary sampling method. The knowledge, attitude and behavior of snakebite among Chinese residents were investigated. Non-parametric test was used to compare the percentage differences in residents' knowledge, attitude and behavior of snakebite, and generalized linear regression analysis was used to analyze the influencing factors, and the vulnerability factors of snakebite patients were comprehensively analyzed. RESULTS: A total of 6338 subjects were included in this study, of which 68.4% were males, and 58.6% were farmers, workers and service personnel. The median total score of knowledge, attitude, and behavior was 26 (22,36). The patients who were improperly treated after injury were ligation proximal to the affected area (23.43%), squeezing (21.82%), and oral and suction wounds (8.74%). Did not go to hospital due to poverty (1351 cases) and did not receive antivenom (2068 cases). There were 21.32% and 32.63%, respectively. Among 4270 patients injected with antivenom 30.7% were vaccinated within 2 h. Among the patients who went to the hospital for treatment (4987), 75.0% arrived at the hospital within 6 h; Among the 4,761 patients who made emergency calls, 37.4% were treated within 0.5 h. CONCLUSIONS: Snakebite patients in China have weak knowledge about snakebite, low awareness of medical treatment, lack of correct prevention and emergency treatment measures, dependence on folk remedies, poor housing and so on. In addition, there are low availability of antivenoms and unreasonable distribution of medical resources in some areas of China. Multisectoral and multidisciplinary cooperation should be developed to prevent and control snakebites in order to reduce the burden caused by snakebites.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Mordeduras de Serpentes , Mordeduras de Serpentes/epidemiologia , Mordeduras de Serpentes/terapia , Humanos , China/epidemiologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Antivenenos/uso terapêutico , Fatores de Risco , Inquéritos e Questionários , Idoso
3.
BMC Emerg Med ; 23(1): 128, 2023 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-37919639

RESUMO

OBJECTIVES: We aim to understand the current situation of the first aid ability and training needs of Chinese medical personnel to provide a scientific basis for formulating the contents and methods of emergency medical rescue training and thereby improve the first aid level of Chinese medical personnel. METHODS: A cross-sectional survey was conducted between June 2022 and February 2023 using a two-stage cluster sampling method with a structured questionnaire sent to medical workers in 12 provinces in China. 14,527 questionnaires were included in this study. Data were collected on demographic characteristics, first aid knowledge and skills, and training needs. Variance analysis was used to compare the difference between the first aid ability and training needs of medical staff in different hospitals, and multiple linear regression analysis was carried out to evaluate first aid ability and training needs. RESULT: The study included 6041 patients (41.6%) in tertiary hospitals, 5838 patients (40.2%) in secondary hospitals, and 2648 patients (18.2%) in primary hospitals. There were significant differences in the first aid ability and training needs of medical staff in hospitals of different levels (p < 0.001). The score of first aid knowledge and skills in tertiary hospitals was the highest (209.7 ± 45.0), and the score of training needs in primary hospitals was the highest (240.6 ± 44.0). There was a significant correlation between first aid ability and training needs score (p < 0.001). Multiple linear regression analysis shows that geographic region, age, work tenure, gender, job title, department, professional title, monthly income, and hospital level are the influencing factors of training demand. CONCLUSION: Medical staff in primary hospitals generally have low first aid knowledge and skills and a strong willingness to train. Therefore, it is imperative to strengthen the training of first aid ability and research training strategies. The level of the hospital is closely related to the level of first aid, so it is necessary to recognize the commonalities and differences in medical staff's demand for first aid knowledge and skills and carry out targeted education and training.


Assuntos
Primeiros Socorros , Corpo Clínico , Humanos , Estudos Transversais , Inquéritos e Questionários , Centros de Atenção Terciária
4.
BMC Complement Altern Med ; 18(1): 235, 2018 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-30092797

RESUMO

BACKGROUND: Sotetsuflavone is isolated from Cycas revoluta Thunb., which has biological activity against tumors. However, the anti-proliferative effects of sotetsuflavone on A549 cells and its mechanism are not fully elucidated. METHODS: This study investigated the mechanisms of growth inhibition, cell cycle arrest and apoptosis in non-small cell lung cancer A549 cells induced by sotetsuflavone and evaluated whether sotetsuflavone can be safely utilized by humans as therapeutic agent. RESULTS: We found that sotetsuflavone had significant antiproliferative activity against A549 cells. At the same time, the reactive oxygen species (ROS) content increased while the mitochondrial membrane potential and the ratio of Bcl-2/Bax decreased. Cleaved caspase-3, cleaved caspase-9, cytochrome C and Bax expression increased, and Cyclin D1, CDK4, cleaved caspase-8 and Bcl-2 expression decreased. Interestingly, we demonstrated that sotetsuflavone could effectively inhibit the G0/G1 cycle progression, and then induce the endogenous apoptosis pathway. Our results show that sotetsuflavone could inhibit the growth of A549 cells by up-regulating intracellular ROS levels and causing the mitochondrial membrane potential to collapse, inducing G0/G1 phase arrest and endogenous apoptosis. CONCLUSIONS: In short, we confirm that sotetsuflavone had an inhibitory effect on A549 cells and discovered that it causes apoptosis of A549 lung cancer cells. Sotetsuflavone may be used as a novel candidate for anti-tumor therapy in patients with lung cancer.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Flavonas/farmacologia , Mitocôndrias/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Células A549 , Antineoplásicos/química , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cycas/química , Flavonas/química , Humanos , Extratos Vegetais/química
5.
J Glob Health ; 14: 04096, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38726547

RESUMO

Background: This study aimed to investigate attitudes towards health education on snakebites and to identify the influencing factors among Chinese residents. Additionally, we proposed effective health education strategies for snakebite management. Methods: Between May 2022 and February 2023, we conducted a nationwide cross-sectional questionnaire survey using a multistage sampling method with supplementary snowball sampling. We used descriptive analysis, χ2 tests, and univariable and multivariable binary logistic regression models to analyse the data. Results: We included 56 669 respondents in the analysis. The average score for snakebite knowledge was 12.13 ± 5.26 points, with a maximum score of 28. Among the respondents, 72.66 and 63.03% of the residents believed that it was necessary to disseminate knowledge about snakebites and expressed a willingness to receive snakebite training, respectively. Respondents from the northeast region, respondents with a higher education level, and respondents with higher scores for snakebite knowledge, health knowledge, health skills, and social-psychological adjustment skills exhibited more positive attitudes towards snakebite knowledge dissemination and training. Conversely, respondents from eastern or southern China, respondents older than 60, and respondents who lived in rudimentary housing conditions showed a lower perception of the need for snakebite knowledge dissemination and were less willing to participate in snakebite knowledge and skill training. Conclusions: Generally, Chinese residents have positive attitudes towards snakebite knowledge dissemination and training. However, the public lacks sufficient knowledge about snakebites. Therefore, we should pay close attention to areas south of the Yangtze River to strengthen snakebite health education using engaging formats that align with residents' interests, such as short videos or television programmes, in an attempt to and ultimately improve health literacy and prevention awareness.


Assuntos
Educação em Saúde , Conhecimentos, Atitudes e Prática em Saúde , Mordeduras de Serpentes , Humanos , Mordeduras de Serpentes/psicologia , Mordeduras de Serpentes/prevenção & controle , Estudos Transversais , Masculino , Feminino , China/epidemiologia , Adulto , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem , Idoso , Adolescente
6.
Int J Public Health ; 68: 1605548, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37205044

RESUMO

Objective: Observational epidemiological studies have shown a link between obesity and sepsis, but any causal relationship is not clear. Our study aimed to explore the correlation and causal relationship between body mass index and sepsis by a two-sample Mendelian randomization (MR). Methods: In large sample genome-wide association studies, single-nucleotide polymorphisms related to body mass index were screened as instrumental variables. Three MR methods, MR-Egger regression, weighted median estimator, and inverse variance-weighted, were used to evaluate the causal relationship between body mass index and sepsis. Odds ratio (OR) and 95% confidence interval (CI) were used as the evaluation index of causality, and sensitivity analyses were conducted to assess pleiotropy and instrument validity. Results: By two-sample MR, the inverse variance weighting method results suggested that increased body mass index was associated with an increased risk of sepsis (odds ratio 1.32; 95% CI 1.21-1.44; p = 1.37 × 10-9) and streptococcal septicemia (OR 1.46; 95% CI 1.11-1.91; p = 0.007), but there was no causal relationship with puerperal sepsis (OR, 1.06; 95% CI, 0.87-1.28; p = 0.577). Sensitivity analysis was consistent with the results, and there was no heterogeneity and level of pleiotropy. Conclusion: Our study supports a causal relationship between body mass index and sepsis. Proper control of body mass index may prevent sepsis.


Assuntos
Estudo de Associação Genômica Ampla , Sepse , Humanos , Índice de Massa Corporal , Análise da Randomização Mendeliana/métodos , Causalidade , Sepse/epidemiologia , Sepse/genética
7.
Int J Public Health ; 68: 1606311, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37965630

RESUMO

Objective: To conduct a bibliometric analysis of the global snakebite literature to provide a reference for the future development of snakebite research. Methods: The Web of Science citation analysis tools, VOSviewer and CiteSpace V were used to carry out the bibliometric analysis of the literature and generate visualization maps. Results: The number of publications has increased at a considerably accelerated rate in the past 8 years. Nine distinct cooperation clusters were formed between institutions and countries. Keyword clustering yielded nine well-structured clusters covering two major topics, i.e., snakebite envenoming and antivenom. Burstiness detection revealed eight keywords with strong emergence, including neglected tropical diseases, Elapidae, Viperidae, and Russell's viper, which have sustained popularity up to the present. Conclusion: Current research on snakebites has gradually garnered attention from the academic community. Cooperation papers between nations severely affected by snakebite and those with higher economic status received more attention. The continued exploration of therapeutic mechanisms, the development of antivenoms or alternative medicines, and primary prevention of snakebites to ensure the safety of populations in impoverished regions should be prioritized by international scholars. The epidemiological evidence and the timely translation of research findings should be valued by policymakers.


Assuntos
Mordeduras de Serpentes , Humanos , Mordeduras de Serpentes/tratamento farmacológico , Mordeduras de Serpentes/prevenção & controle , Antivenenos/uso terapêutico
8.
World J Emerg Med ; 14(5): 367-371, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37908800

RESUMO

BACKGROUND: Several observational studies have shown an association between homocysteine (Hcy) levels and chronic obstructive pulmonary disease (COPD), but causal relationships are not clear. Our study aimed to explore the causal relationship between plasma Hcy and COPD by two-sample Mendelian randomization (MR). METHODS: A two-sample MR study was performed to infer the causal link. Genetically predicted plasma Hcy was selected as an instrumental variable (IV) from published genome-wide association study (GWAS) meta-analyses. COPD with different etiologies was extracted as outcome variables from other GWAS meta-analyses. The main MR analysis was performed using the inverse-variance weighted (IVW) method. Additional analyses were further performed using Cochran's Q-test and MR-Egger regression to evaluate the heterogeneity or horizontal pleiotropy of our findings. RESULTS: MR analysis showed no significant association between plasma Hcy and COPD. The results of the groups were consistent with the sensitivity analysis and repeated analysis, without heterogeneity or horizontal pleiotropy. The IVW results showed COPD hospital admissions (odds ratio [OR] 1.06, 95% confidence interval [CI] 0.91-1.24, P=0.42), asthma/COPD (OR 0.97, 95% CI 0.89-1.06, P=0.55), COPD-related chronic infection (OR 1.50, 95% CI 0.57-3.99, P=0.41), COPD/asthma/interstitial lung disease (ILD)-related pneumonia or pneumonia-derived septicemia (OR 0.93, 95% CI 0.86-1.02, P=0.13), and COPD-related respiratory insufficiency (OR 1.00, 95% CI 0.7-1.44, P=0.99). CONCLUSION: There is no direct causal relationship between plasma Hcy and COPD in our study. As Hcy is known to have deleterious effects on endothelial function and vascular homeostasis, further studies are needed to investigate whether additional factors mediate the association between Hcy and COPD.

9.
Int J Public Health ; 68: 1606601, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38146482

RESUMO

Objectives: This study aimed to determine the current status of the knowledge of diagnosis and treatment of snakebites among medical staff in China and its influencing factors. Methods: A cross-sectional survey of 12,581 medical staff was conducted in 12 provinces in China between June 2022 and February 2023. We analyzed the results using descriptive statistics, T-tests or analysis of variance, and a generalized linear model. Results: The average score of snakebite diagnosis and treatment knowledge among medical staff in China was 3.15 ± 2.15 out of a total score of 12. Through a generalized linear regression model, we found that gender, occupation, region, hospital level, work department, work tenure, training received in the diagnosis and treatment of snakebite, experience in snakebite diagnosis and treatment, availability of antivenom in the unit, and self-evaluation of snakebite treatment ability all affected the medical staff's scores of snakebite diagnosis and treatment knowledge. Conclusion: The knowledge level of snakebite diagnosis and treatment among Chinese medical staff is generally low, so it is imperative to conduct standardized snakebite diagnosis and treatment training for medical staff.


Assuntos
Competência Clínica , Mordeduras de Serpentes , Humanos , Antivenenos , China , Estudos Transversais , Mordeduras de Serpentes/diagnóstico , Mordeduras de Serpentes/epidemiologia , Mordeduras de Serpentes/terapia
10.
Am J Transl Res ; 13(8): 9853-9859, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34540121

RESUMO

OBJECTIVE: In this study, we focused on obese patients (Body Mass Index (BMI) ≥30 kg/m2) and compared the efficacy and safety of etomidate or propofol-mediated anesthesia induction followed by intubation and sevoflurane maintenance during endoscopic retrograde cholangiopancreatography (ERCP). METHODS: A total of 180 patients were computer-randomized into a propofol group or an etomidate group, with 90 cases in each group. Patients received anesthesia induction by etomidate or propofol followed by intubation and sevoflurane maintenance during ERCP. Baseline characteristics, information about procedure-related time and satisfaction, and adverse events were collected and compared between the etomidate group and propofol group. RESULTS: Baseline characteristics of both groups were similar. The propofol group had a longer time of intraoperative SpO2 <95% (etomidate group vs propofol group, 0.07±0.47 min vs 0.24±0.87 min, P-value = 0.019), higher frequency of SpO2 <95% for any period of time (etomidate group vs propofol group, 2.22% vs 11.11%, P-value = 0.032), and higher frequency of transient hypotension (etomidate group vs propofol group, 1.11% vs 8.89%, P-value = 0.034). The etomidate group had longer induction time and recovery time than the propofol group with P-values of 0.019 and 0.004, respectively. CONCLUSION: In obese patients who underwent ERCP and needed intubation, etomidate appears better than propofol for anesthesia induction followed by anesthesia maintenance of sevoflurane.

11.
Am J Transl Res ; 13(10): 11999-12005, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34786134

RESUMO

OBJECT: In this study, we aim to investigate if there exists some change in the pathogenicity of SARS-CoV-2 by comparing the clinical characteristics between recent imported patients and earlier local patients. METHODS: 227 local COVID-19 patients diagnosed before February 15, 2020 (local group) and 23 imported COVID-19 patients diagnosed between July 1, 2020, and January 15, 2021 (imported group) were included in this study. Baseline characteristics and characteristics of computed tomography (CT), routine blood test, liver functions, and infectious markers upon admission were collected and compared. RESULTS: The neutrophil-to-lymphocyte ratio (NLR) of the imported group was 3.21 ± 1.25, which was significantly higher than that of the local group (2.55 ± 1.19) with a P-value of 0.030. The concentration of C-reactive protein of the imported group was 12.34 ± 5.25, which was significantly higher than that of the local group (7.76 ± 6.54 mg/L) with a P-value of 0.0005. No significant difference was observed in the rest characteristics. CONCLUSION: The recent imported cases had higher NLR and C-reactive protein levels than the earlier local cases, indicating that the pathogenicity of SARS-CoV-2 is getting worse during the pandemic.

12.
Front Pharmacol ; 12: 518406, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33994999

RESUMO

Marsdeniae tenacissimae Caulis is a traditional Chinese medicine, named Tongguanteng (TGT), that is often used for the adjuvant treatment of cancer. In our previous study, we reported that an ethyl acetate extract of TGT had inhibitory effects against adenocarcinoma A549 cells growth. To identify the components of TGT with anti-tumor activity and to elucidate their underlying mechanisms of action, we developed a technique for isolating compounds, which was then followed by cytotoxicity screening, network pharmacology analysis, and cellular and molecular experiments. We isolated a total of 19 compounds from a TGT ethyl acetate extract. Two novel steroidal saponins were assessed using an ultra-performance liquid chromatography-photodiode array coupled with quadrupole time-of-flight mass (UPLC-ESI-Q/TOF-MS). Then, we screened these constituents for anti-cancer activity against non-small cell lung cancer (NSCLC) in vitro and obtained six target compounds. Furthermore, a compound-target-pathway network of these six bioactive ingredients was constructed to elucidate the potential pathways that controlled anticancer effects. Approximately 205 putative targets that were associated with TGT, as well as 270 putative targets that were related to NSCLC, were obtained from online databases and target prediction software. Protein-protein interaction networks for drugs as well as disease putative targets were generated, and 18 candidate targets were detected based on topological features. In addition, pathway enrichment analysis was performed to identify related pathways, including PI3K/AKT, VEGF, and EGFR tyrosine kinase inhibitor resistance, which are all related to metabolic processes and intrinsic apoptotic pathways involving reactive oxygen species (ROS). Then, various cellular experiments were conducted to validate drug-target mechanisms that had been predicted using network pharmacology analysis. The experimental results showed the four C21 steroidal saponins could upregulate Bax and downregulate Bcl-2 expression, thereby changing the mitochondrial membrane potential, producing ROS, and releasing cytochrome C, which finally activated caspase-3, caspase-9, and caspase-8, all of which induced apoptosis in A549 cells. In addition, these components also downregulated the expression of MMP-2 and MMP-9 proteins, further weakening their degradation of extracellular matrix components and type IV collagen, and inhibiting the migration and invasion of A549 cells. Our study elucidated the chemical composition and underlying anti-tumor mechanism of TGT, which may be utilized in the treatment of lung cancer.

13.
J Ethnopharmacol ; 251: 112535, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-31926315

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Marsdenia tenacissima is a traditional Chinese medicine that has been used since the Ming dynasty. It is famous for its apoptotic effects on lung cancer. However, limited information is available about the underlying mechanisms. AIM OF THE STUDY: We aimed to determine the mechanisms by which different organic M. tenacissima extracts induce apoptosis in lung cancer cells. MATERIALS AND METHODS: PubMed and CNKI databases were screened for M. tenacissima components that may targets lung cancer; 223 components were selected for drug-like and pharmacokinetic analysis. Moreover, the inhibitory effect of different extracts of M. tenacissima on tumor cells was illustrated using CCK-8 and apoptosis assays, and intracellular [Ca2+] was measured. The in vivo effects were examined by body weight, tumor pathology, and TUNEL staining analysis in a Lewis lung carcinoma mouse model. In vivo levels of the Ca2+ signaling-related proteins Calmodulin, CaMKⅡ, p-CaMKⅡ, MEK1/2, p-MEK1/2, ERK, and p-ERK were measured by Western blot. RESULTS: Petroleum ether and ethyl acetate extracts of M. tenacissima have stronger inhibitory effects than other extracts on lung cancer cells, with IC50 values of 0.35 ± 0.04 mg/ml and 0.29 ± 0.02 mg/ml for LLC cells and 0.56 ± 0.05 mg/ml and 0.85 ± 0.04 mg/ml for A549 cells, respectively. Compared with the normal control group, A549 and LLC cells of treatment groups exhibited morphological changes typical of apoptosis, and the apoptosis rate was significantly higher, as determined by flow cytometry. Furthermore, the i[Ca2+] changed accordingly, causing a decrease in vivo in Calmodulin, CaMKⅡ, p-CaMKⅡ, p-MEK1/2 and p-ERK levels. CONCLUSIONS: M. tenacissima induces apoptosis, both in vitro and in vivo. Hydrophobic extracts are most effective; they increase i[Ca2+], decrease intracellular Calmodulin, CaMKⅡ, p-CaMKⅡ, p-MEK1/2 and p-ERK levels, and activate the apoptotic cascade.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Sinalização do Cálcio/efeitos dos fármacos , Neoplasias Pulmonares/metabolismo , Marsdenia , Extratos Vegetais/farmacologia , Animais , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Calmodulina/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Camundongos Endogâmicos C57BL , Extratos Vegetais/uso terapêutico , Transdução de Sinais/efeitos dos fármacos
14.
Front Pharmacol ; 10: 1460, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31920653

RESUMO

Non-small cell lung cancer (NSCLC) is a globally scaled disease with a high incidence and high associated mortality rate. Autophagy is one of the important physiological activities that helps to control cell survival, influences the dynamics of cell death, and which plays a crucial role in the pathophysiology of NSCLC. Sotetsuflavone is a naturally derived and occurring flavonoid, and previous studies have demonstrated that sotetsuflavone possesses potential anti-cancer activities. However, whether or not sotetsuflavone induces autophagy, as well as has effects and influences cell death in NSCLC cells remains unclear. Thus, in our study, we examined and elucidated the roles and underlying mechanisms of sotetsuflavone upon the dynamics of autophagy in NSCLC in vivo and in vitro. The results indicated that sotetsuflavone was able to inhibit proliferation, migration, and invasion of NSCLC cells. Mechanistically, sotetsuflavone was able to induce apoptosis by increasing the levels of expression of cytochrome C, cleaved-caspase 3, cleaved-caspase 9, and Bax, and contrastingly decreased levels of expression of Bcl-2. In addition, we also found that decreased levels of expression of cyclin D1 and CDK4 caused arrest of the G0/G1 phases of the cell cycle. Furthermore, we also found that sotetsuflavone could induce autophagy which in turn can play a cytoprotective effect on apoptosis in NSCLC. Sotetsuflavone-induced autophagy appeared related to the blocking of the PI3K/Akt/mTOR pathway. Our in vivo study demonstrated that sotetsuflavone significantly inhibited the growth of xenograft model inoculated A549 tumor with high a degree of safety. Taken together, these findings suggest that sotetsuflavone induces autophagy in NSCLC cells through its effects upon blocking of the PI3K/Akt/mTOR signaling pathways. Our study may provide a theoretical basis for future clinical applications of sotetsuflavone and its use as a chemotherapeutic agent for treatment of NSCLC.

15.
Cell Death Discov ; 4: 26, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29531823

RESUMO

Epithelial-mesenchymal transition (EMT) is associated with tumor invasion and metastasis, and offers insight into novel strategies for cancer treatment. Sotetsuflavone was isolated from Cycas revolute, which has excellent anticancer activity in the early stages. The present study aims to evaluate the anti-metastatic potential of sotetsuflavone in vitro. Our data demonstrated that sotetsuflavone inhibits metastasis of A549 cells, and EMT. This inhibition was reflected in the upregulation of E-cadherin, and downregulation of N-cadherin, vimentin, and Snail. Mechanistically, our study demonstrated that HIF-1α played an important role in the anti-metastatic effect of sotetsuflavone in non-small-cell lung cancer A549 cells. Sotetsuflavone not only mediated VEGF expression but also downregulated VEGF and upregulated angiostatin, and simultaneously affected the expression of MMPs and decreased MMP-9 and MMP-13 expression. More importantly, HIF-1α expression may be regulated by the inhibition of PI3K/AKT and TNF-α/NF-κB pathways. These results suggest that sotetsuflavone can reverse EMT, thereby inhibiting the migration and invasion of A549 cells. This process may be associated with both PI3K/AKT and TNF-α/NF-κB pathways, and sotetsuflavone may be efficacious in the treatment of non-small-cell lung cancer.

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