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Dietary intake of natural substances to regulate physiological functions is currently regarded as a potential way of promoting health. As one of the recommended dietary ingredients, phytosterols that are natural bioactive compounds distributed in plants have received increasing attention for their health effects. Phytosterols have attracted great attention from scientists because of many physiological functions, for example, cholesterol-lowering, anticancer, anti-inflammatory, and immunomodulatory effects. In addition, the physiological functions of phytosterols, the purification, structure analysis, synthesis, and food application of phytosterols have been widely studied. Nowadays, many bioactivities of phytosterols have been assessed in vivo and in vitro. However, the mechanisms of their pharmacological activities are not yet fully understood, and in-depth investigation of the relationship between structure and function is crucial. Therefore, a contemporaneous overview of the extraction, beneficial properties, and the mechanisms, as well as the current states of phytosterol application, in the food field of phytosterols is provided in this review.
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Exposure to mustard gas can cause damage or death to human beings, depending on the concentration and duration. Thus, developing high-performance mustard-gas sensors is highly needed for early warning. Herein, ultrathin WO3 nanosheet-supported Pd nanoparticles hybrids (WO3 NSs/Pd) are prepared as chemiresistive sulfur mustard simulant (e.g., 2-chloroethyl ethyl sulfide, 2-CEES) gas sensors. As a result, the optimal WO3 NSs/Pd-2 (2 wt % of Pd)-based sensor exhibits a high response of 8.5 and a rapid response/recovery time of 9/92 s toward 700 ppb 2-CEES at 260 °C. The detection limit could be as low as 15 ppb with a response of 1.4. Moreover, WO3 NSs/Pd-2 shows good repeatability, 30-day operating stability, and good selectivity. In WO3 NSs/Pd-2, ultrathin WO3 NSs are rich in oxygen vacancies, offer more sites to adsorb oxygen species, and make their size close to or even within the thickness of the so-called electron depletion layer, thus inducing a large resistance change (response). Moreover, strong metal-support interactions (SMSIs) between WO3 NSs and Pd nanoparticles enhance the catalytic redox reaction performance, thereby achieving a superior sensing performance toward 2-CEES. These findings in this work provide a new approach to optimize the sensing performance of a chemiresistive sensor by constructing SMSIs in ultrathin metal oxides.
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Gás de Mostarda , Óxidos , Paládio , Tungstênio , Tungstênio/química , Paládio/química , Gás de Mostarda/análise , Gás de Mostarda/química , Gás de Mostarda/análogos & derivados , Óxidos/química , Limite de Detecção , Nanopartículas Metálicas/química , Nanoestruturas/química , Substâncias para a Guerra Química/análise , Substâncias para a Guerra Química/química , Técnicas Eletroquímicas/métodosRESUMO
Long noncoding RNAs (lncRNAs) play important roles in various biological processes. However, the regulatory roles of lncRNAs underlying fruit development have not been extensively studied. The pumpkin (Cucurbita spp.) is a preferred model for understanding the molecular mechanisms regulating fruit development because of its variable shape and size and large inferior ovary. Here, we performed strand-specific transcriptome sequencing on pumpkin (Cucurbita maxima "Rimu") fruits at 6 developmental stages and identified 5,425 reliably expressed lncRNAs. Among the 332 lncRNAs that were differentially expressed during fruit development, the lncRNA MSTRG.44863.1 was identified as a negative regulator of pumpkin fruit development. MSTRG.44863.1 showed a relatively high expression level and an obvious period-specific expression pattern. Transient overexpression and silencing of MSTRG.44863.1 significantly increased and decreased the content of 1-aminocyclopropane carboxylic acid (a precursor of ethylene) and ethylene production, respectively. RNA pull-down and microscale thermophoresis assays further revealed that MSTRG.44863.1 can interact with S-adenosyl-L-methionine synthetase (SAMS), an enzyme in the ethylene synthesis pathway. Considering that ethylene negatively regulates fruit development, these results indicate that MSTRG.44863.1 plays an important role in the regulation of pumpkin fruit development, possibly through interacting with SAMS and affecting ethylene synthesis. Overall, our findings provide a rich resource for further study of fruit-related lncRNAs while offering insights into the regulation of fruit development in plants.
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Cucurbita , Frutas , Regulação da Expressão Gênica de Plantas , Metionina Adenosiltransferase , RNA Longo não Codificante , Cucurbita/genética , Cucurbita/crescimento & desenvolvimento , Etilenos/metabolismo , Frutas/genética , Frutas/crescimento & desenvolvimento , Frutas/metabolismo , Metionina Adenosiltransferase/genética , Metionina Adenosiltransferase/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA de Plantas/genética , RNA de Plantas/metabolismo , S-Adenosilmetionina/metabolismoRESUMO
OBJECTIVES: Unilateral complete cleft lip and palate (UCCLP) is one of the most severe clinical subtypes among cleft lip and palate (CLP), making repair surgery and subsequent orthodontic treatment particularly challenging. Presurgical nasoalveolar molding (PNAM) has shown conflicting and heterogeneous results in the treatment of UCCLP patients, raising questions about whether the diversity in alveolar anatomical morphology among these patients plays a role in the effectiveness of PNAM treatment. MATERIALS AND METHODS: We collected 90 digital maxillary models of infants with UCCLP and performed mathematical clustering analysis, including principal component analysis (PCA), decision tree modeling, and area under the ROC Curve (AUC) analysis, to classify alveolar morphology and identify key measurements. We also conducted clinical evaluations to assess the association between the alveolar morphology and CLP treatment outcomes. RESULTS: Using mathematical clustering analysis, we classified the alveolar morphology into three distinct types: average form, horizontal form, and longitudinal form. The decision tree model, AUC analysis, and comparison analysis revealed that four measurements (Trans ACG-ACL, ML length, MG length and Inc length) were essential for clustering the alveolar morphology of infants with UCCLP. Furthermore, the blinded clinical evaluation indicated that UCCLP patients with alveolar segments of horizontal form had the lowest treatment outcomes. CONCLUSION: Overall, our findings establish a novel quantitative classification system for the morphology of alveolar bone in infants with UCCLP and suggest that this classification may be associated with the outcomes of CLP treatment. CLINICAL RELEVANCE: The multidisciplinary CLP team should thoroughly evaluate and classify the specific alveolar morphology when administering PNAM to infants with UCCLP.
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Fenda Labial , Fissura Palatina , Lactente , Humanos , Fenda Labial/cirurgia , Fissura Palatina/cirurgia , Nariz , Cuidados Pré-Operatórios/métodosRESUMO
To investigate the effects of allo-Treg cells, allo-NK cells, and their mixtures in different proportions on Graft-versus-host disease (GVHD) in bone marrow transplant mouse model. In this study, C57BL/6 mice were used as donors, and 6 Gy dose of 60Co γ was used as the receptor of BALB/c mice. The recipient mice were divided into NC (normal saline), CON (bone marrow cells), NK (bone marrow cells + NK cells), Treg (bone marrow cells + Treg cells), NK+ Treg (1:1) (bone marrow cells +1:1 ratio of Treg cells, NK cells), and NK+ Treg (6:1) (bone marrow cells +1:6 ratio of Treg cells, NK cells), according to the different injection mode through the tail vein. The differences of white blood cell (WBC), platelet (PLT), clinical manifestations, and GVHD score of target organs (liver, lung, small intestine) in each group after transplantation were observed, and the differences of chimerism rate and survival rate in each group at 28 days after transplantation were compared. The interaction between Treg cells and NK cells in different proportions (1:1, 1:2, 1:6, 1:12) was investigated in vitro in mouse erythroleukemia (MEL) cells of mouse erythroleukemia. The results showed that at the 28th day of transplantation, the clinical manifestations and GVHD scores of target organs of mice in NK+ Treg (1:1) group and NK+ Treg (6:1) group were significantly lower than other groups (P < 0.05); the WBC and PLT counts were significantly higher than other groups (P < 0.05), and the survival time was significantly longer than other groups (P < 0.05); the clinical manifestations and GVHD scores of each target organ in NK+ Treg (1:1) group were significantly lower than those in NK+ Treg (6:1) group (P < 0.05); the chimerism rate of each group was >90% on day 28 after transplantation. In vitro experiments showed that the inhibition of Treg cells on NK cell killing activity was dose-dependent, and the proportion of 1:6 and 1:12, killing activity of NK cell was significantly lower than that of groups 1:1 and 1:2 (P < 0.05), which showed that allo-NK and allo-Treg alone had a significant effect on the improvement of GVHD after transplantation, and Treg cells inhibited the killing activity of NK cells by direct contact and showed a dose-dependent effect.
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Doença Enxerto-Hospedeiro , Leucemia Eritroblástica Aguda , Animais , Camundongos , Linfócitos T Reguladores/transplante , Camundongos Endogâmicos C57BL , Transplante de Medula Óssea/métodos , Camundongos Endogâmicos BALB CRESUMO
Iron (Fe) is essential for DNA synthesis, photosynthesis and respiration of plants. The demand for Fe substantially increases during legumes-rhizobia symbiotic nitrogen fixation because of the synthesis of leghemoglobin in the host and Fe-containing proteins in bacteroids. However, the mechanism by which plant controls iron transport to nodules remains largely unknown. Here we demonstrate that GmYSL7 serves as a key regulator controlling Fe uptake from root to nodule and distribution in soybean nodules. GmYSL7 is Fe responsive and GmYSL7 transports iron across the membrane and into the infected cells of nodules. Alterations of GmYSL7 substantially affect iron distribution between root and nodule, resulting in defective growth of nodules and reduced nitrogenase activity. GmYSL7 knockout increases the expression of GmbHLH300, a transcription factor required for Fe response of nodules. Overexpression of GmbHLH300 decreases nodule number, nitrogenase activity and Fe content in nodules. Remarkably, GmbHLH300 directly binds to the promoters of ENOD93 and GmLbs, which regulate nodule number and nitrogenase activity, and represses their transcription. Our data reveal a new role of GmYSL7 in controlling Fe transport from host root to nodule and Fe distribution in nodule cells, and uncover a molecular mechanism by which Fe affects nodule number and nitrogenase activity.
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Glycine max , Ferro , Glycine max/metabolismo , Ferro/metabolismo , Nódulos Radiculares de Plantas/genética , Nódulos Radiculares de Plantas/metabolismo , Transporte Biológico , Fixação de Nitrogênio/genética , Nitrogenase/genética , Nitrogenase/metabolismo , Simbiose/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
OBJECTIVE: To explore the effect of rapid rehabilitation nursing on inflammation and liver function in patients with primary liver cancer (PLC) after laparoscopic radical resection. METHODS: A total of 124 PLC patients who underwent laparoscopic radical surgery in the Zhuji People's Hospital of Zhejiang Province from April 2019 to July 2021 were enrolled in this retrospective study. Among them, 65 patients who received rapid rehabilitation nursing were assigned into the observation group (OG), and the other 59 with routine nursing were considered to be the control group (CG). The pain before operation (T0), 3 days after operation (T1) and 7 days after operation (T2) was evaluated by visual analogue scale (VAS). The perioperative related indexes and nursing satisfaction were compared. The levels of liver function indexes alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and inflammatory factors C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured before operation, 1 day and 7 days after operation. Finally, the incidence of postoperative complications was counted, the 6-month survival rate of both groups of patients was compared. RESULTS: There was no obvious difference in VAS scores between the two groups at T0 (P>0.050), but the VAS scores at T1 and T2 in the OG were lower than those in the CG (P<0.001). There was no marked difference in the total operation time. Compared with the CG, the time to first exhaust, catheter indwelling and hospitalization in the OG were shorter (P<0.001) and the nursing satisfaction rate was higher (P<0.05). There was no obvious difference in ALT, AST and TBIL on the 1st day after operation (P>0.05); however, on the 7th day after operation, ALT and AST were lower while TBIL was higher in the OG (all P<0.05). There was no marked difference in CRP, IL-6 and TNF-α between the two groups on postoperative day 1 (P>0.05), but the levels were lower in the OG than those in the CG on postoperative day 7 (all P<0.05), and the total incidence of adverse reactions in the OG was lower (P<0.05). There was no statistical difference in the postoperative survival rate between both groups of patients (P>0.05). Age, number of lesions, tumor size, Child-Pugh grade, AST, TBIL, CRP, IL-6, TNF-α were associated with the survival rate of patients. CONCLUSION: Rapid rehabilitation nursing can effectively reduce adverse reactions after laparoscopic radical resection of PLC. Thus, it has a high application value in future clinical treatment.
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BACKGROUND: Bimaxillary surgery is often performed for class III malocclusion, and its complex influence on the upper airway has been well considered. The aim of this research was to provide a scaled formula between upper airway volume changes and bone movements in Class III patients after orthognathic surgery. MATERIALS AND METHODS: Using a retrospective study design, the investigators enrolled a total of 30 class III malocclusion patients who were undergoing bimaxillary surgery as the study subjects. The subjects included 15 males and 15 females, and their average age was 23.3 ± 3.4 years. CBCT (cone beam tomography) was performed both before and one year after the surgery for each patient. The changes in the soft palate, tongue and upper airway were measured by using CBCT data that was collected before and after surgery. 3D superimposition of CBCT was performed to calculate three-dimensional jaw movements. A multiple regression analysis was used to calculate the quantitative relationship between airway volume changes and jaw movements. RESULTS: The nasopharynx airway volume was observed to be increased by 1064.0 ± 1336.2 mm3, whereas the retropalatal and retroglossal airway volumes were observed to be decreased by 1399.0 ± 2881.6 mm3 and 1433.8 ± 3043.4 mm3, respectively, after the surgery. One millimetre forward and downward movements of the PNS resulted in increases of 626.90 mm3 and 392.18 mm3 in nasopharynx airway volume, respectively. Moreover, one millimetre retrogression of the B point caused decreases of 314.6 mm3 and 656.6 mm3 in the retropalatal and retroglossal airway volume, respectively. The changes in the soft palate contributed to the decrease in the retropalatal airway volume, whereas the tongue compensated for the decrease in the retroglossal airway volume. CONCLUSION: The movements of the PNS and B points could be used to predict upper airway volumetric changes in Class III patients after maxillary advancement and mandibular setback.
Assuntos
Má Oclusão Classe III de Angle , Procedimentos Cirúrgicos Ortognáticos , Adulto , Cefalometria/métodos , Tomografia Computadorizada de Feixe Cônico/métodos , Feminino , Humanos , Masculino , Má Oclusão Classe III de Angle/diagnóstico por imagem , Má Oclusão Classe III de Angle/cirurgia , Mandíbula/cirurgia , Maxila/diagnóstico por imagem , Maxila/cirurgia , Procedimentos Cirúrgicos Ortognáticos/métodos , Faringe/diagnóstico por imagem , Estudos Retrospectivos , Adulto JovemRESUMO
Sphingosine 1-phosphate receptor 1 (S1PR1) plays a pivotal role in mediating trafficking and migration of immune cells. Previous reports also identify S1PR1 as an important susceptibility gene of asthma and other autoimmune disorders. However, little has been known about the regulatory mechanism of S1PR1 expression. Thus we systematically investigated the transcriptional regulation of S1PR1 in this study. Promoter activity of S1PR1 gene was carefully screened using series of pGL3-Basic reporter vectors, containing full length (range from transcription start site to upstream -1 kb region) or several truncated fragments of S1PR1 promoter. We identified an area (from -29 to -12 bp) of the S1PR1 promoter as the minimal promoter region. Bioinformatics prediction results showed that several transcription factors were recruited to these sites. EMSA and ChIP assays demonstrated the transcriptional factor STAT1 could bind to the region. We also found that the level of S1PR1 level was significantly reduced when STAT1 was knocked-down. Consistent with the reduction of S1PR1 caused by depletion of STAT1, overexpression of STAT1 resulted in up-regulation of S1PR1. In addition, both mRNA and protein levels of S1PR1 were increased when STAT1 was activated by IFN-γ, and decreased when STAT1 was inhibited by fludarabine. Besides, the levels of STAT1 and S1PR1 expression were positively correlated in peripheral blood leukocytes derived from 41 healthy individuals. Our study showed that transcription factor STAT1 could bind to upstream region of -29 bp to -12 bp of the S1PR1 promoter and stimulate the expression of S1PR1.
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Regiões Promotoras Genéticas/genética , Fator de Transcrição STAT1/genética , Receptores de Esfingosina-1-Fosfato/genética , Transcrição Gênica/genética , Linhagem Celular , Linhagem Celular Tumoral , Regulação da Expressão Gênica/genética , Genes Reporter/genética , Células HEK293 , Células HeLa , Humanos , Interferon gama/genética , RNA Mensageiro/genética , Regulação para Cima/genéticaRESUMO
The long-acting glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 suppresses food intake and decreases body weight. However, the mediating site(s) of action of the anorectic effects induced by peripheral administration of GLP-1R agonists are not well known. The present study investigated the effects of bilateral lesions of the central nucleus of the amygdala (CeA) on the suppression of chow and high-sucrose food intake by exendin-4 in rats. Adult male Sprague-Dawley rats with bilateral sham or electrolytic lesions (400 µA; 25 s) of the CeA were used for this experiment. No significant difference was found in the daily chow intake and high-sucrose food intake in rats with CeA lesion compared to sham-operated rats. Bilateral lesions of the CeA significantly attenuated the suppression of high-sucrose food intake by i.p. exendin-4, but not the suppression of chow intake. These results suggest that a mediating role of the CeA on the peripheral effects of exendin-4.
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Núcleo Central da Amígdala/efeitos dos fármacos , Exenatida/farmacologia , Comportamento Alimentar/efeitos dos fármacos , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/metabolismo , Animais , Regulação do Apetite/fisiologia , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Exenatida/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Hipoglicemiantes/farmacologia , Masculino , Peptídeos/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
Alisol B-23-acetate (AB23A), a tetracyclic triterpenoid isolated from the rhizome of Alisma orientale, has been reported to exert anti-proliferative activities in human colon, ovarian and gastric cancer cells. However, the anti-cancer effect of this compound on human lung cancer cells has not yet been thoroughly elucidated. In the present study, we investigated the effects of AB23A on the cell viability and apoptosis in human lung cancer A549 and NCI-H292â¯cells. The results indicated that AB23A inhibited the growth of A549 and NCI-H292â¯cells in dose- and time-dependent manner, however, there was only weak cytotoxicity on normal bronchial epithelial cells. The induction of apoptosis by AB23A was demonstrated by DAPI and annexin-V-FITC/PI staining. Further investigation revealed that AB23A decreased mitochondrial membrane potential (MMP) and up regulated reactive oxygen species (ROS) level. Meanwhile, the increased Bax/Bcl-2 ratio, activated caspase-3, caspase-9 and PARP were observed. In addition, AB23A increased the release of cytochrome c from mitochondria and the translocation of apoptotic inducing factor (AIF) into nuclei. Taken together, these results indicated that AB23A induced apoptosis by activating the intrinsic pathway, and suggested that AB23A can be used as a potential modulating agent in lung cancer.
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Alisma/química , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Colestenonas/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Colestenonas/química , Colestenonas/isolamento & purificação , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Mitocôndrias/metabolismo , Conformação Molecular , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
Recent studies have shown that Cab45s, belonging to the CREC family, can fight against apoptosis in the cancer cell lines. Here, we report that Cab45s may involve in neuronal apoptosis at the early stage of intracerebral hemorrhage (ICH) in pathophysiology. We found that expression of Cab45s was enhanced in areas contiguous to hematoma following ICH in adult rats, and that so were the expressions of Glucose-regulated protein 78 (GRP78), pro-apoptotic Bcl-2-associated X protein (Bax) and active caspase-3. In vitro, coimmunoprecipitation analysis indicated the interaction between Cab45s and GRP78. Depletion of Cab45s attenuated the expression of GRP78, but increased the expressions of Bax and caspase-3 in PC12 cells treated with hemin, which finally promoted apoptosis. Together, these results reveal that Cab45s might exert its anti-apoptotic function against neuronal apoptosis. Thus, the study may provide evidences for regulating Cab45s as a potentially reliable treatment for the secondary damage following ICH.
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Proteínas de Ligação ao Cálcio/metabolismo , Hemorragia Cerebral/metabolismo , Hemorragia Cerebral/fisiopatologia , Animais , Apoptose/efeitos dos fármacos , Proteínas de Ligação ao Cálcio/genética , Caspase 3/metabolismo , Proteínas de Choque Térmico/metabolismo , Masculino , Neurônios/efeitos dos fármacos , Células PC12 , Ratos , Ratos Sprague-Dawley , Proteína X Associada a bcl-2/metabolismoRESUMO
The Cucurbita genus contains several economically important species in the Cucurbitaceae family. Here, we report high-quality genome sequences of C. maxima and C. moschata and provide evidence supporting an allotetraploidization event in Cucurbita. We are able to partition the genome into two homoeologous subgenomes based on different genetic distances to melon, cucumber, and watermelon in the Benincaseae tribe. We estimate that the two diploid progenitors successively diverged from Benincaseae around 31 and 26 million years ago (Mya), respectively, and the allotetraploidization happened at some point between 26 Mya and 3 Mya, the estimated date when C. maxima and C. moschata diverged. The subgenomes have largely maintained the chromosome structures of their diploid progenitors. Such long-term karyotype stability after polyploidization has not been commonly observed in plant polyploids. The two subgenomes have retained similar numbers of genes, and neither subgenome is globally dominant in gene expression. Allele-specific expression analysis in the C. maxima × C. moschata interspecific F1 hybrid and their two parents indicates the predominance of trans-regulatory effects underlying expression divergence of the parents, and detects transgressive gene expression changes in the hybrid correlated with heterosis in important agronomic traits. Our study provides insights into polyploid genome evolution and valuable resources for genetic improvement of cucurbit crops.
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Instabilidade Cromossômica , Cromossomos de Plantas , Cucurbita/genética , Evolução Molecular , Genoma de Planta , Cariótipo , Tetraploidia , Análise de Sequência de DNARESUMO
Dehydrobruceine B (DHB) is a quassinoid isolated from Brucea javanica. We have shown previously that DHB induced apoptosis on two kinds of lung cancer cell lines, A549 and NCI-H292. In the present study, we investigated the interactions of DHB and cisplatin (CDDP) on apoptotic-related cancer cell death. Synergistic effects on cell proliferation and apoptosis were observed when A549 cells were treated with DHB plus CDDP. DHB combined CDDP exposure increased depolarization of mitochondrial membrane potential (MMP) and release of cytochrome c from mitochondria into the cytoplasm. The combination treatment also enhanced protein expression of Bax, reduced the protein levels of Bcl-xL and Bcl-2, and increased the cleavage of caspase-3, caspase-9 and poly (ADP-ribose) polymerase (PARP). These results indicated that DHB sensitized A549 cells to cisplatin by regulating the mitochondrial apoptotic pathway. High constitutive expression of Nrf2 was found in A549 cells, which enhance the resistance of cancer cells to chemotherapeutic agents including cisplatin. DHB reduced the protein levels of Nrf2 and its target genes, which may contribute to the increase of intracellular ROS level, consequently, induced mitochondria apoptosis. These results generated a rationale for further investigation of DHB combined with CDDP as a potential therapeutic strategy in lung cancer.
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Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos/farmacologia , Proteínas Reguladoras de Apoptose/efeitos dos fármacos , Cisplatino/farmacologia , Quassinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Células A549 , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Brucea/química , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Fator 2 Relacionado a NF-E2/biossíntese , Fator 2 Relacionado a NF-E2/genéticaRESUMO
BACKGROUND: Brucea javanica is an effective traditional medicine listed in Chinese Pharmacopoeia. In China, the seed oil of B. javanica has long been used as commercially available drug for the treatment of tumor in clinic. Dehydrobruceine B (DHB) is a quassinoid isolated from B. javanica. PURPOSE: The aim of the present study is to investigate the apoptotic effects induced by DHB in human lung cancer A549 and NCI-H292 cells. The involvement of a mitochondria-mediated intrinsic pathway in the pro-apoptotic action of DHB was also investigated. MATERIAL AND METHODS: Cell viability was determined by MTT assay. Cell cycle and apoptosis were assessed by flow cytometry analysis. Mitochondrial membrane potential (MMP) was examined through JC-1 staining. The protein translocation in cells was examined by immunostaining. The expression levels of proteins which are closely related to mitochondria-mediated apoptosis pathway were measured by immunoblot analysis. RESULTS: Treatment with DHB decreased cell viability, induced apoptosis and blocked cell cycle at S phase. DHB-induced apoptosis was found to be mediated through mitochondrial intrinsic pathway, evidenced by the loss of MMP, the release of cytochrome c into cytosol, and the cleavage of caspase-9, caspase-3 and poly (ADP-ribose) polymerase (PARP). CONCLUSION: DHB triggers apoptosis in A549 and NCI-H292 cells via mitochondrial pathway, making it a promising candidate as a therapeutic agent for lung carcinoma.
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Apoptose/efeitos dos fármacos , Neoplasias Pulmonares/patologia , Mitocôndrias/efeitos dos fármacos , Quassinas/química , Caspase 3/metabolismo , Caspase 9/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , China , Citocromos c/metabolismo , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismoRESUMO
In order to study whether Tnfaip3 is related to stress response and further to find it's genetic regulation, we use C57BL/6J (B6) and DBA/2 (D2) mice to built the model of chronic unpredictable mild stress. RT-PCR, Western blotting and immunohistochemistry were used for studying the expression variation of Tnfaip3 in hippocampus tissue of B6 and D2 mice after being stressed. We found that the expression of Tnfaip3 was more remarkably increased in chronic unpredictable stress models than that in untreated mice (P<0.05). It is indicated that Tnfaip3 might take part in the process of stress response. The expression of Tnfaip3 is regulated by a cis-acting quantitative trait locus (cis-eQTL). We identified 5 genes are controlled by Tnfaip3 and the expression of 64 genes highly associated with Tnfaip3, 9 of those have formerly been participate in stress related pathways. In order to estimate the relationship between Tnfaip3 and its downstream genes or network members, we transfected SH-SY5Y cells with Tnfaip3 siRNA leading to down-regulation of Tnfaip3 mRNA. We confirmed a significant influence of Tnfaip3 depletion on the expression of Tsc22d3, Pex7, Rap2a, Slc2a3, and Gap43. These validated downstream genes and members of Tnfaip3 gene network provide us new insight into the biological mechanisms of Tnfaip3 in chronic unpredictable stress.
Assuntos
Cisteína Endopeptidases/fisiologia , Regulação da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Estresse Fisiológico/genética , Animais , Linhagem Celular Tumoral , Cisteína Endopeptidases/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Camundongos , Locos de Características Quantitativas , Proteína 3 Induzida por Fator de Necrose Tumoral alfaRESUMO
Two new compounds (1-2), including a bisabolane-type sesquiterpenoid (1), one new diphenyl ether derivative (2), together with 23 known compounds (3-25), were isolated from the fruits of Phyllanthus emblica. Their structures were elucidated by detailed spectroscopic analysis. All the isolated compounds were screened for the DPPH scavenging effects and cytoprotective effects against H2O2 induced PC12 cells injury. Compounds 12-15 showed significant DPPH scavenging effects with the IC50 values in the range of 3.25-4.18 µM. Among these potential antioxidants, compound 14 improved the survival of PC12 cells after H2O2 exposure without showing any cytotoxicity at the tested concentrations.
Assuntos
Sobrevivência Celular/efeitos dos fármacos , Citoproteção/efeitos dos fármacos , Peróxido de Hidrogênio/toxicidade , Phyllanthus emblica/química , Extratos Vegetais/química , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Sobrevivência Celular/fisiologia , Citoproteção/fisiologia , Relação Dose-Resposta a Droga , Frutas , Células PC12 , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , RatosRESUMO
Podoimbricatin A (1), a diterpenoid possessing an unprecedented 6/6/5/6-fused tetracyclic ring system, and podoimbricatin B (2), a new abietane-type diterpenoid, together with four previously reported diterpenoids and a cyclic peptide were isolated from the twigs and leaves of Podocarpus imbricatus. Their structures were established on the basis of extensive spectroscopic analyses and the relative configuration of 1 was confirmed by single-crystal X-ray diffraction analysis. A plausible biogenetic pathway involving hetero-Diels-Alder cycloaddition as a key reaction is proposed for 1. Compounds 1, 5, and 7 showed inhibitory effects against the A549 and NCI-H292 cancer cell lines.
Assuntos
Abietanos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Folhas de Planta/química , Caules de Planta/química , Traqueófitas/química , Abietanos/química , Abietanos/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Modelos Moleculares , Conformação Molecular , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: To analyze the auditory capability of preschool children before and after cochlear implantation using meaningful auditory integration scale (MAIS) questionnaire. METHODS: Eighty-two prelingually deaf patients participated in this study. They received a cochlear implant at the age of 3 to 6 years and 11 months. The audiologists who were trained for the research used the MAIS questionnaire. Audiologists asked for the parents' answers and recorded all the information about the device using (Q1,2) and the patient's spontaneous auditory behavioural responses including spontaneous alerting to sound Q3 approximately 6 and deriving meaning from sound (Q7 approximately 10). The evaluation was performed before operation and 1 , 3, 6 months, 1, 1.5, 2 years after switch-on. RESULTS: The scores of question 1a and 1b were not significantly different among the different periods after switch-on. The scores of question 2 to 10 were significantly different among the different periods after switch-on. CONCLUSIONS: Considerable variability across subjects' auditory ability after cochlear implantation was noted. Most of the patients showed no consistent response to sound in everyday life before implantation. After cochlear implantation, a significant increase in auditory capability occurred. The children demonstrated faster development of device using relative to spontaneous alerting to sound and deriving meaning from sound.