RESUMO
Fatty acids are an important source of energy and a key component of phospholipids in membranes and organelles. Saturated fatty acids (SFAs) are converted into unsaturated fatty acids (UFAs) by stearoyl Co-A desaturase (SCD), an enzyme active in cancer. Here, we studied how the dynamics between SFAs and UFAs regulated by SCD impacts ovarian cancer cell survival and tumor progression. SCD depletion or inhibition caused lower levels of UFAs vs. SFAs and altered fatty acyl chain plasticity, as demonstrated by lipidomics and stimulated Raman scattering (SRS) microscopy. Further, increased levels of SFAs resulting from SCD knockdown triggered endoplasmic reticulum (ER) stress response with brisk activation of IRE1α/XBP1 and PERK/eIF2α/ATF4 axes. Disorganized ER membrane was visualized by electron microscopy and SRS imaging in ovarian cancer cells in which SCD was knocked down. The induction of long-term mild ER stress or short-time severe ER stress by the increased levels of SFAs and loss of UFAs led to cell death. However, ER stress and apoptosis could be readily rescued by supplementation with UFAs and reequilibration of SFA/UFA levels. The effects of SCD knockdown or inhibition observed in vitro translated into suppression of intraperitoneal tumor growth in ovarian cancer xenograft models. Furthermore, a combined intervention using an SCD inhibitor and an SFA-enriched diet initiated ER stress in tumors growing in vivo and potently blocked their dissemination. In all, our data support SCD as a key regulator of the cancer cell fate under metabolic stress and point to treatment strategies targeting the lipid balance.
Assuntos
Sobrevivência Celular , Endorribonucleases , Ácidos Graxos Insaturados , Neoplasias Ovarianas , Progressão da Doença , Ácidos Graxos Dessaturases , Ácidos Graxos/farmacologia , Ácidos Graxos Insaturados/farmacologia , Feminino , Humanos , Fosfolipídeos , Proteínas Serina-Treonina Quinases , Estearoil-CoA Dessaturase/metabolismoRESUMO
BACKGROUND: Traditional Chinese medicine (TCM) massage has a better effect on treating infant diarrhea compared to medical treatment. The TCM doctors need to be trained to master professional massage techniques. Traditional Chinese massage training relies on the students' understanding ability, and cannot accurately record the students' operating information. This situation leads to insufficient clinical massage skills of the students. OBJECTIVE: This paper proposes a novel massage training platform to quantitatively perceive the massage techniques of students. METHODS: The paper proposed two types of flexible array sensors, which are arranged and placed into the bionic baby according to the position of the human acupoints. The massage techniques of the training object can be analyzed and evaluated during the massage process by studying the voltage from pressure sensors when the participants massage the bionic infant. RESULTS: A medical student was invited to conduct the massage training experiment, and the massage information included the operating strength, massage frequency and the massage direction, which were recorded and analyzed through the training platform. CONCLUSION: The platform can perceive the parameters related to the massage technique of students and can be used for medical training.
Assuntos
Diarreia/terapia , Massagem/educação , Modelos Anatômicos , Pontos de Acupuntura , Competência Clínica , Humanos , LactenteRESUMO
In this study, series of CexZryMnzO2/r-Al2O3 catalysts were prepared by impregnation method and explored to co-purification of NOx and Hg0 at low temperature. The physical and chemical properties of the catalysts were investigated by XRD, BET, FTIR, NH3-TPD, H2-TPR, and XPS. The experimental results showed that 10% Ce0.2Zr0.3Mn0.5O2/r-Al2O3 yielded higher conversion on co-purification of NOx and Hg0 than the other prepared catalysts at low temperature, especially at 200-300 °C. 91% and 97% convert rate of NOx and Hg0 were obtained, respectively, when 10% Ce0.2Zr0.3Mn0.5O2/r-Al2O3 catalyst was used at 250 °C. Moreover, the presence of H2O slightly decreased the removal of NOx and Hg0 owing to the competitive adsorption of H2O and Hg0. When SO2 was added, the removal of Hg0 first increased slightly and then presented a decrease due to the generation of SO3 and (NH4)2SO4. The results of NH3-TPD indicated that the strong acid of 10% Ce0.2Zr0.3Mn0.5O2/r-Al2O3 improved its high-temperature activity. XPS and H2-TPR results showed there were high-valence Mn and Ce species in 10% Ce0.2Zr0.3Mn0.5O2/r-Al2O3, which could effectively promote the removal of NOx and Hg0. Therefore, the mechanisms of Hg0 and NOx removal were proposed as Hg (ad) + [O] â HgO (ad), and 2NH3/NH4+ (ad) + NO2 (ad) + NO (g) â 2 N2 + 3H2O/2H+, respectively. Graphical abstract á .
Assuntos
Poluentes Atmosféricos/química , Temperatura Baixa , Gases/química , Mercúrio/química , Óxidos de Nitrogênio/química , Adsorção , Óxido de Alumínio/química , Catálise , OxirreduçãoRESUMO
Ovarian cancer is the most lethal gynecological malignancy. Patients usually have poor prognosis because of late diagnosis, relapse, and chemoresistance. It is pressing to seek novel agent for the treatment of ovarian cancer. Neferine is a bisbenzylisoquinoline alkaloid isolated from the embryos of lotus (Nelumbo nucifera). In this study, we investigated the antitumor effect of neferine on ovarian cancer cells. We found that neferine exhibited growth-inhibitory effect on human ovarian cancer cells, whereas showing less cytotoxic to non-malignant fallopian tube epithelial cells. Furthermore, we demonstrated that neferine induced autophagy and inactivated the mTOR pathway. Finally, we found that both p38 MAPK and JNK signaling pathways were activated by neferine treatment and contributed to the induction of autophagy in ovarian cancer cells. In conclusion, our findings showed that neferine induced autophagy of human ovarian cancer cells via p38 MAPK/JNK activation. Neferine may be explored as a promising antitumoral agent in ovarian cancer.
Assuntos
Autofagia/efeitos dos fármacos , Benzilisoquinolinas/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neoplasias Ovarianas/tratamento farmacológico , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Feminino , Humanos , Nelumbo/química , Neoplasias Ovarianas/metabolismo , Extratos Vegetais/farmacologia , Serina-Treonina Quinases TOR/metabolismoRESUMO
In order to explore the temporal and spatial variation of nutrients and chlorophyll a and their relationship in the Three Gorges Reservoir, nutrients and chlorophyll a were monitored chronically and frequently in Gaoyang Lake in Pengxi River in the Three Gorges Reservoir from May 2013 to May 2014. The study showed that the thermal stratification affected the vertical distribution of chlorophyll a and nutrients. The water thermal stratification in Gaoyang Lake occurred in early March and disappeared in the middle of September, and there was no stratification in winter ( November to February of the second year). Chlorophyll a in the surface water increased from 14.92 microg x L(-1) to 183.73 microg x L(-1) and then the chlorophyll a concentration decreased with the increasing depth of the mixing layer ( epilimnion) in the spring of 2014. Furthermore, phosphorus concentration was significantly different among layers when the water stratified and the concentration gradient of TP between the surface and the bottom was (0.18 +/- 0.04) mg x L(-1). When water was not stratified in Gaoyang Lake, the surface, middle and bottom layers had similar concentrations of chlorophyll a and nutrients, respectively. Nitrate N and dissolved phosphorus were the major components of TN and TP, respectively, during the high water level period in Gaoyang Lake with nitrate N accounting for 71.4%-95.4% of TN and dissolved phosphorus 42.7%-94.% of TP, showing that the backwater from the mainstream of Yangtze was the main source of nitrate N and dissolved phosphorus in Gaoyang Lake.
Assuntos
Clorofila/análise , Lagos/química , Nitratos/análise , Fósforo/análise , Rios/química , China , Clorofila A , Monitoramento Ambiental , Estações do Ano , Análise Espaço-TemporalRESUMO
Despite the advances of adjuvant chemotherapy and significant improvement of survival, the prognosis for patients with osteosarcoma is generally poor. The search for more effective anti-osteosarcoma agents is necessary and urgent. Here we report that perifosine induces cell apoptosis and growth inhibition in cultured human osteosarcoma cells. Perifosine blocks Akt/mTOR complex 1 (mTORC1) signaling, while promoting caspase-3, c-Jun N-terminal kinases (JNK), and p53 activation. Further, perifosine inhibits survivin expression probably by disrupting its association with heat shock protein-90 (HSP-90). These signaling changes together were responsible for a marked increase of osteosarcoma cell apoptosis and growth inhibition. Finally, we found that a low dose of perifosine enhanced etoposide- or doxorubicin-induced anti-OS cells activity. The results together suggest that perifosine might be used as a novel and effective anti-osteosarcoma agent.
Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fosforilcolina/análogos & derivados , Antineoplásicos/farmacologia , Western Blotting , Caspase 3/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Doxorrubicina/farmacologia , Sinergismo Farmacológico , Ensaio de Imunoadsorção Enzimática , Etoposídeo/farmacologia , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina , Complexos Multiproteicos/metabolismo , Osteossarcoma/tratamento farmacológico , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Fosforilcolina/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
OBJECTIVE: To assess the effect of Danqi Huogan Capsule in protecting the liver, promoting the circulation and removing blood clots in patients with chronic hepatitis B (CHB). METHODS: A total of 104 CHB patients were randomized into two groups. Routine therapies for liver protection were given in the control group (n=50), and Danqi Huogan Capsule was administered in the therapeutic group (n=54) in addition to the routine therapies. The changes in the clinical symptoms, physical signs, liver functions, and hemorrheology were observed after the 3-month therapies. RESULTS: Danqi Huogan Capsule treatment obvious improved the clinical symptoms, physical signs and liver functions of the patients (P<0.01), and significantly decreased the hematocrit, low-shear blood viscosity, plasma viscosity and index of red blood cell aggregation (P<0.05). CONCLUSION: Danqi Huogan Capsule is effective in protecting the liver, improving hemorrheology, promoting the blood circulation and removing clots in patients with chronic hepatitis B.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Fitoterapia , Adolescente , Adulto , Idoso , Feminino , Hemorreologia , Hepatite B Crônica/sangue , Hepatite B Crônica/fisiopatologia , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: To explore the significance of the combination of factor analysis and systematic cluster analysis in classification of traditional Chinese medical syndromes in patients with posthepatitic cirrhosis, and to provide a scientific basis for the criterion of the classification. METHODS: We designed a clinical questionnaire according to the clinical characteristics and the demands of traditional Chinese medical information collection for patients with posthepatitic cirrhosis. By means of clinical epidemiological research, with the four diagnosis methods for clinical information collection of traditional Chinese medicine, symptoms, physical signs, tongue conditions and pulse conditions in 310 patients with posthepatitic cirrhosis were collected, and the characteristics of traditional Chinese medical syndromes in these patients were explored with statistical methods, such as factor analysis, varimax and systematic cluster analysis. RESULTS: Analyzed by factor analysis and systematic cluster analysis with SPSS 11.0, the traditional Chinese medical syndromes in 287 of the 310 cases (92.58%) of posthepatitic cirrhosis could be classified. The syndromes could be divided into 7 categories, which were internal accumulation of damp-heat (55 cases), insufficiency of the spleen with overabundance of dampness (74 cases), accumulation of blood stasis plus deficiency of liver-yin and kidney-yin (73 cases), accumulation of blood stasis plus deficiency of both blood and qi (40 cases), deficiency of both blood and qi (16 cases), deficiency of yin and blood heat (6 cases) and stagnation of the liver-qi and deficiency of the spleen (23 cases). The traditional Chinese medical syndromes in the other 23 cases could not be classified. CONCLUSIONS: The clinical information collected with the four diagnostic methods of traditional Chinese medicine can be classified into different categories with the factor analysis and systematic cluster analysis. The factor analysis and systematic cluster analysis can reveal the characteristics and regularity of traditional Chinese medical syndromes in patients with posthepatitic cirrhosis in a way, and have value in researching the syndromes of traditional Chinese medicine.
Assuntos
Diagnóstico Diferencial , Cirrose Hepática/diagnóstico , Medicina Tradicional Chinesa , Adulto , Análise por Conglomerados , Análise Fatorial , Feminino , Humanos , Cirrose Hepática/classificação , Cirrose Hepática/terapia , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , SíndromeRESUMO
OBJECTIVE: To explore the characteristics of traditional Chinese medical syndrome (TCM syndrome) of hepatocirrhosis. METHODS: Clinical information from the four diagnosis methods of traditional Chinese medicine (TCM) and related laboratorial indexes were systematically collected from 223 hepatocirrhosis cases, and the multi-statistical methods including systematic cluster analysis, principal component analysis, stepwise discrimination and variance analysis were made with the software SAS 6.11. RESULTS: Multi-analysis showed that there were 3 categories of syndrome characteristics. Type 1 (134 cases): damp heat, blood stasis, deficiency of liver and spleen Qi; Type 2 (62 cases): deficiency of both Qi and Yin with severe deficiency of Qi, heat with severe dampness, blood stasis; Type 3 (27 cases): deficiency of both Qi and Yin with severe deficiency of Yin, stasis and heat or dampness. Analysis of the changes of the related laboratorial indexes among the three types of syndrome showed that Type 1 mainly manifested asthenia syndrome with sthenia syndrome, and its indexes of AST, ALT, GGT levels were markedly higher than those of Type 2 and Type 3, both of which mainly showed sthenia syndrome with asthenia syndrome, and that Type 3 was in active inflammation, deficiency of both Qi and Yin (deficiency of Yin > deficiency of Qi), and its FN, Alb, FV, FVII, PLT, PCT levels were obviously reduced. CONCLUSION: The multi-statistical methods can reveal the characteristics and regularity of TCM syndrome of hepatocirrhosis, and the 3 categories of syndrome characteristics basically conform to clinical manifestations. The result of TCM syndrome distribution and laboratorial indexes infer that damp heat is the pathological basis of hepatocirrhosis, and the degree of liver function disorder and liver damage may be the pathological basis of deficiency of Yin of both liver and kidney.