Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 59
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Eur Rev Med Pharmacol Sci ; 27(1): 66-73, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36647851

RESUMO

OBJECTIVE: Non-coding RNAs occupy a significant fraction of the human genome, and their biological significance during the pathological process is proved. More and more lncRNAs are reported in cancer research. MATERIALS AND METHODS: To investigate the non-coding RNA's biological relevance with cutaneous skin melanoma, we first compared the survival analysis by combining the most differentially expressed mRNA and non-coding RNA expression values. RESULTS: The result showed that the abundantly expressed mRNAs and lncRNAs have significant effects on the survival of patients. Compared to the mRNAs, these lncRNAs have more impact on the progress of cutaneous skin melanoma. Thus, we combined the two types of RNA factors having significant effects as risk factors to construct the diagnosis model, and the survival analysis confirmed the robustness of the diagnosis model. CONCLUSIONS: In summary, a list of eight lncRNA and five mRNA expression signatures can be used to improve the prognosis prediction of cutaneous skin melanoma, as well as help us to understand the pathogenic mechanism and provide a hint for targeting therapy.


Assuntos
Melanoma , RNA Longo não Codificante , Neoplasias Cutâneas , Humanos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Melanoma/diagnóstico , Melanoma/genética , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Melanoma Maligno Cutâneo
2.
J Physiol Pharmacol ; 72(2)2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34374659

RESUMO

The Asian ginseng root (Panax ginseng C.A. Meyer) is a very commonly used herbal medicine worldwide. Ginseng fruit, including the berry (or pulp) and seed, is also valuable for several health conditions including immunostimulation and cancer chemoprevention. In this study, the anticancer and anti-proliferative effects of the extracts of ginseng berry and seed were evaluated. The ginsenosides in the ginseng berry concentrate (GBC) and ginseng seed extract (GSE) were analyzed. We then evaluated their anti-colorectal cancer potentials, including antiproliferation, cell cycle arrest, and apoptotic induction. Further investigation consisted of the berry's adaptive immune responses, such as the actions on the differentiation of T helper cells Treg, Th1, and Th17. The major constituents in GBC were ginsenosides Re and Rd, which can be compared to those in the root. The GBC significantly inhibited colon cancer cell growth, and its anti-proliferative effect involved mechanisms including G2/M cell cycle arrest via upregulation of cyclin A and induction of apoptosis via regulation of apoptotic related gene expressions. GBC also downregulated the expressions of pro-inflammatory cytokine genes. For the adaptive immune responses, GBC did not influence Th1 and Treg cell differentiation but significantly inhibited Th17 cell differentiation and thus regulated the balance of Th17/Treg for adaptive immunity. Although no ginsenoside was detected in the GSE, interestingly, it obviously enhanced colon cancer cell proliferation with the underlined details to be determined. Our results suggested that GBC is a promising dietary supplement for cancer chemoprevention and immunomodulation.


Assuntos
Neoplasias do Colo , Panax , Apoptose , Ciclo Celular , Diferenciação Celular , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/prevenção & controle , Medicamentos de Ervas Chinesas , Frutas , Humanos , Inflamação/tratamento farmacológico , Inflamação/prevenção & controle , Extratos Vegetais/farmacologia
3.
Clin Transl Oncol ; 22(7): 1013-1022, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31650468

RESUMO

OBJECTIVE: Chronic inflammation is recognized as a risk factor for colorectal cancer (CRC) development. Baicalin (BI), a major constituent in an anti-inflammatory herb Scutellaria baicalensis, can be biotransformed into baicalein (BE) by the intestinal microbiota. We evaluated the anti-inflammation and anti-CRC effects of the metabolite BE. METHODS: The in vitro biotransformation by human intestinal microbiota from BI into BE has been determined with HPLC. Using a gut-specific ApcMin/+ mouse model, the effects of oral BE on the life span, organ index, and tumor multiplicity were evaluated. The expressions of inflammatory cytokines were determined using ELISA. To verify the in vivo data, the anti-inflammatory and antiproliferative effects of BE were determined with an in vitro cell model. RESULTS: HPLC analysis showed that BI was quickly transformed into BE by the intestinal microbiota. Oral BE (30 mg/kg/day) significantly increased the life span, from 125.2 to 218.4 days (P < 0.01%). BE treatment also decreased intestine index and increased spleen index. Compared with the model group, following BE treatment, tumor numbers were significantly reduced in the small intestine and colon (P < 0.01, P < 0.05, respectively). In the gut tissues, BE treatment significantly reduced inflammatory cytokine levels such as IL-1ß, IL-2, IL-6, IL-10, G-CSF, and GM-CSF. In vitro data supported our in vivo results that the anti-CRC effects of BE were via the inhibition of gut inflammation and induction of cancer cell death. CONCLUSION: Our results suggest that the parent compound BI can be quickly converted into its microbial metabolite BE, which has stronger bioactive effects than BI. Baicalein is an active chemopreventive metabolite for inflammatory associated CRC.


Assuntos
Antioxidantes/farmacologia , Colo/efeitos dos fármacos , Neoplasias Colorretais/patologia , Citocinas/efeitos dos fármacos , Flavanonas/farmacologia , Intestino Delgado/efeitos dos fármacos , Proteína da Polipose Adenomatosa do Colo/genética , Animais , Colo/imunologia , Colo/patologia , Neoplasias Colorretais/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Flavanonas/metabolismo , Flavonoides/metabolismo , Microbioma Gastrointestinal , Células HT29 , Humanos , Inflamação/metabolismo , Neoplasias Intestinais/genética , Neoplasias Intestinais/patologia , Intestino Delgado/imunologia , Intestino Delgado/patologia , Longevidade , Camundongos , Carga Tumoral
4.
Eur Rev Med Pharmacol Sci ; 23(20): 8813-8822, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31696468

RESUMO

OBJECTIVE: To investigate the role of microRNA-15 (miR-15) in the progression of bladder cancer (BC) cell and its underlying mechanism. PATIENTS AND METHODS: Human BC specimens were collected from BC patients during operations. BC cell lines (T24, BIU87, and HT1376) and normal uroepithelial cell lines SV-HUV-1 were cultured. The abilities of cell proliferation and invasion were detected by Methyl thiazolyl tetrazolium (MTT) and transwell assay, respectively. Additionally, the relevant mRNA and protein expressions were measured by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), Western blot and immunohistochemistry, respectively. Furthermore, the luciferase reporter assay was used to verify the target gene of miR-15. Besides, Xenograft tumor formation assay was performed to confirm the effect of miR-15 on tumor growth. RESULTS: A low expression of miR-15 was detected by qRT-PCR, whereas the high expression of B cell-specific Moloney murine leukemia virus integration site 1 (BMI1) was detected by immunocytochemical assay in BC tissues. Moreover, miR-15 expression and BMI1 expression were significantly associated with the overall survival of BC patients. MTT and transwell assay results stated that the up-regulation of miR-15 inhibited BC cell proliferation, migration, and invasion. BMI-1 was verified as a direct target of miR-15 in BC using Luciferase reporter assay. Besides, miR-15 regulated epithelial-mesenchymal transition (EMT)-related makers, protein kinase B (AKT), and the phosphorylation of AKT protein levels in BC using the Western blot assay. Xenograft tumor formation assay indicated that the over-expression of miR-15 inhibited the tumor growth. CONCLUSIONS: We stated that miR-15 suppressed BC cell progression by targeting BMI1 through the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway, which provided a potential target for BC treatment.


Assuntos
MicroRNAs/metabolismo , Complexo Repressor Polycomb 1/metabolismo , Transdução de Sinais , Neoplasias da Bexiga Urinária/patologia , Animais , Antagomirs/metabolismo , Antagomirs/uso terapêutico , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Feminino , Humanos , Masculino , Camundongos , Camundongos Nus , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinase/metabolismo , Complexo Repressor Polycomb 1/química , Complexo Repressor Polycomb 1/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/mortalidade , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Eur Rev Med Pharmacol Sci ; 23(3): 1184-1195, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30779088

RESUMO

OBJECTIVE: This study aimed to explore the candidate genes and their potential mechanism in childhood acute lymphoblastic leukemia (cALL). MATERIALS AND METHODS: Differentially expressed genes (DEGs) were screened from GSE67684 (treatment), GSE28460 (relapse), and GSE60926 (relapse). The expression of AEBP1 at different stages of cALL was analyzed followed by functional enrichment analysis of its co-expressed genes. Expression of AEBP1 was determined in different leukemia cell lines and knocked down in Jurkat cells. Cell behaviors as well as the expression of p53, Bax, and Bcl-2 were also evaluated after silencing AEBP1 in Jurkat cells. RESULTS: Two clusters: Profile 1 (downward) and Profile 26 (upward) were identified in GSE67684, and 53 Profile 1-specific DEGs were identified compared with DEGs in GSE28460 and GSE60926. AEBP1 was one of these genes and was significantly downregulated after treatment but upregulated in relapse samples. Functional enrichment analysis revealed that AEBP1 co-expressed genes were significantly enriched in GO terms including immune response, blood coagulation etc. and in the hematopoietic cell lineage and PI3K/Akt signaling pathways. AEBP1 was significantly increased in leukemia cell lines, especially in Jurkat cells, compared with the Pbmc cells. Silencing AEBP1 markedly reduced proliferation and induced cell cycle arrest in Jurkat cells, but also promoted apoptosis of Jurkat cells. Silencing AEBP1 also inhibited the expression of p53 and Bcl-2 but promoted Bax in Jurkat cells. CONCLUSIONS: AEBP1 was highly-expressed in the diagnosis and relapse cALL, and silencing AEBP1 significantly reduced proliferation but promoted apoptosis in Jurkat cells via a p53-dependent pathway.


Assuntos
Carboxipeptidases/genética , Regulação Leucêmica da Expressão Gênica , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteínas Repressoras/genética , Proteína Supressora de Tumor p53/metabolismo , Apoptose/genética , Ciclo Celular/genética , Proliferação de Células/genética , Criança , Conjuntos de Dados como Assunto , Redes Reguladoras de Genes , Inativação Gênica , Humanos , Células Jurkat , Família Multigênica , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia
6.
Nat Commun ; 10(1): 607, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30723197

RESUMO

Topology-protected surface transport of ultimate thinness in three-dimensional topological insulators (TIs) is breaking new ground in quantum science and technology. Yet a challenge remains on how to disentangle and selectively control surface helical spin transport from the bulk contribution. Here we use the mid-infrared and terahertz (THz) photoexcitation of exclusive intraband transitions to enable ultrafast manipulation of surface THz conductivity in Bi2Se3. The unique, transient electronic state is characterized by frequency-dependent carrier relaxations that directly distinguish the faster surface channel than the bulk with no complication from interband excitations or need for reduced bulk doping. We determine the topological enhancement ratio between bulk and surface scattering rates, i.e., γBS/γSS ~3.80 in equilibrium. The ultra-broadband, wavelength-selective pumping may be applied to emerging topological semimetals for separation and control of the protected transport connected with the Weyl nodes from other bulk bands.

7.
Insect Mol Biol ; 28(1): 23-34, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30058747

RESUMO

Parasitic wasps rely on olfaction to locate their hosts in complex chemical environments. Odorant receptors (ORs) function together with well-conserved odorant coreceptors (ORcos) to determine the sensitivity and specificity of olfactory reception. Campoletis chlorideae (Hymenoptera: Ichneunmonidae) is a solitary larval endoparasitoid of the cotton bollworm, Helicoverpa armigera, and some other noctuid species. To understand the molecular basis of C. chlorideae's olfactory reception, we sequenced the transcriptome of adult male and female heads (including antennae) and identified 211 OR transcripts, with 95 being putatively full length. The tissue expression profiles, as assessed by reverse-transcription PCR, showed that seven ORs were expressed only or more highly in female antennae. Their functions were analysed using the Xenopu slaevis oocyte expression system and two-electrode voltage-clamp recordings. CchlOR62 was tuned to cis-jasmone, which was attractive to female C. chlorideae adults and H. armigera larvae in the subsequent behavioural assays. Further bioassays using caged plants showed that the parasitism rate of H. armigera larvae by C. chlorideae on cis-jasmone-treated tobacco plants was higher than on the control plants. Thus, cis-jasmone appears to be an important infochemical involved in the interactions of plants, H. armigera and C. chlorideae, and CchlOR62 mediates the attractiveness of cis-jasmone to C. chlorideae.


Assuntos
Ciclopentanos/metabolismo , Interações Hospedeiro-Parasita , Mariposas/parasitologia , Oxilipinas/metabolismo , Receptores Odorantes/metabolismo , Vespas/metabolismo , Animais , Antenas de Artrópodes/metabolismo , Feminino , Larva/metabolismo , Larva/parasitologia , Masculino , Mariposas/metabolismo , Controle Biológico de Vetores , Olfato , Nicotiana , Xenopus laevis
8.
Clin. transl. oncol. (Print) ; 20(3): 302-312, mar. 2018. ilus, graf
Artigo em Inglês | IBECS | ID: ibc-171317

RESUMO

Objective. Chronic intestinal inflammation is a risk factor for colorectal cancer (CRC) initiation and development. Diets that are rich in Western style fats have been shown to promote CRC. This study was conducted to investigate the role of intestinal microbiome in American ginseng-mediated CRC chemoprevention in a mouse model. The population and diversity of enteric microbiome were evaluated after the ginseng treatment. Methods. Using an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced gut inflammation and tumorigenesis mouse model, the effects of oral American ginseng on high fat diet-associated enteric pathology were determined. After establishment of a 16S rRNA illumina library from fecal samples, MiSeq sequencing was carried out to reveal the microbial population. The alpha and beta diversities of microbiome were analyzed. Results. American ginseng significantly attenuated AOM/DSS-induced colon inflammation and tumorigenesis by reducing the colitis score and colon tumor multiplicity. The MiSeq results showed that the majority of sequences fell into three phyla: Firmicutes, Bacteroidetes and Verrucomicrobia. Further, two significant abundance shifts at the family level, Bacteroidaceae and Porphyromonadaceae, were identified to support ginseng’s anti-colitis and anti-tumor effects. In addition, alpha and beta diversity data demonstrated that ginseng led to a profound recovery from the AOM/DSS-induced dysbiosis in the microbial community. Conclusion. Our results suggest that the CRC chemopreventive effects of American ginseng are mediated through enteric microbiome population-shift recovery and dysbiosis restoration. Ginseng’s regulation of the microbiome balance contributes to the maintenance of enteric homeostasis (AU)


No disponible


Assuntos
Animais , Camundongos , Microbiota/fisiologia , Panax , Neoplasias Colorretais/prevenção & controle , Doenças Inflamatórias Intestinais/complicações , Substâncias Protetoras/farmacocinética , Extratos Vegetais/farmacocinética , Doenças Inflamatórias Intestinais/tratamento farmacológico , Carcinogênese , RNA Ribossômico 16S/análise , Dieta Hiperlipídica , Modelos Animais de Doenças
9.
Clin Transl Oncol ; 20(3): 302-312, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28808878

RESUMO

OBJECTIVE: Chronic intestinal inflammation is a risk factor for colorectal cancer (CRC) initiation and development. Diets that are rich in Western style fats have been shown to promote CRC. This study was conducted to investigate the role of intestinal microbiome in American ginseng-mediated CRC chemoprevention in a mouse model. The population and diversity of enteric microbiome were evaluated after the ginseng treatment. METHODS: Using an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced gut inflammation and tumorigenesis mouse model, the effects of oral American ginseng on high fat diet-associated enteric pathology were determined. After establishment of a 16S rRNA illumina library from fecal samples, MiSeq sequencing was carried out to reveal the microbial population. The alpha and beta diversities of microbiome were analyzed. RESULTS: American ginseng significantly attenuated AOM/DSS-induced colon inflammation and tumorigenesis by reducing the colitis score and colon tumor multiplicity. The MiSeq results showed that the majority of sequences fell into three phyla: Firmicutes, Bacteroidetes and Verrucomicrobia. Further, two significant abundance shifts at the family level, Bacteroidaceae and Porphyromonadaceae, were identified to support ginseng's anti-colitis and anti-tumor effects. In addition, alpha and beta diversity data demonstrated that ginseng led to a profound recovery from the AOM/DSS-induced dysbiosis in the microbial community. CONCLUSION: Our results suggest that the CRC chemopreventive effects of American ginseng are mediated through enteric microbiome population-shift recovery and dysbiosis restoration. Ginseng's regulation of the microbiome balance contributes to the maintenance of enteric homeostasis.


Assuntos
Carcinogênese/efeitos dos fármacos , Neoplasias do Colo/patologia , Microbioma Gastrointestinal/efeitos dos fármacos , Panax , Extratos Vegetais/farmacologia , Animais , Azoximetano/toxicidade , Carcinogênese/induzido quimicamente , Carcinogênese/patologia , Colite/etiologia , Colite/microbiologia , Colite/patologia , Neoplasias do Colo/etiologia , Neoplasias do Colo/microbiologia , Sulfato de Dextrana/toxicidade , Dieta Hiperlipídica/efeitos adversos , Masculino , Camundongos , Raízes de Plantas
11.
J Neuroendocrinol ; 29(1)2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27917547

RESUMO

Pituitary stalk interruption syndrome (PSIS) is a rare congenital defect manifesting with varying degrees of pituitary hormone deficiency. The signs and symptoms of PSIS during the neonatal period and infancy are often overlooked and therefore diagnosis is delayed. The typical manifestations of PSIS can be detected by magnetic resonance imaging. Several genes in the Wnt, Notch and Shh signalling pathways related to hypothalamic-pituitary development, such as PIT1, PROP1, LHX3/LHX4, PROKR2, OTX2, TGIF and HESX1, have been found to be associated with PSIS. Nevertheless, the aetiology in the majority of cases still remains unknown. In the present review, we provide an overview of clinical features of PSIS and summarise our current understanding of the underlying pathogenic mechanisms for this rare syndrome. Furthermore, we propose future research directions that may help our understanding of the aetiology of PSIS.


Assuntos
Hipotireoidismo Congênito/patologia , Hipófise/patologia , Hormônios Hipofisários/deficiência , Hipotireoidismo Congênito/diagnóstico , Hipotireoidismo Congênito/diagnóstico por imagem , Hipotireoidismo Congênito/genética , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Mutação , Síndrome
12.
Dalton Trans ; 45(7): 3102-10, 2016 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-26777518

RESUMO

Recently, the +2 formal oxidation state in soluble molecular complexes for lanthanides (La-Nd, Sm-Lu) and actinides (Th and U) has been discovered [W. J. Evans, et al., J. Am. Chem. Soc., 2011, 133, 15914; J. Am. Chem. Soc., 2012, 134, 8420; J. Am. Chem. Soc., 2013, 135, 13310; Chem. Sci., 2015, 6, 517]. To explore the nature of the bonding and stabilities of the low-valent actinide complexes, a series of divalent actinide species, [AnCp'3](-) (An[double bond, length as m-dash]Th-Am, Cp' = [η(5)-C5H4(SiMe3)](-)) have been investigated in THF solution using scalar relativistic density functional theory. The electronic structures and electron affinity properties were systematically studied to identify the interactions between the +2 actinide ions and Cp' ligands. The ground state electron configurations for the [AnCp'3](-) species are [ThCp'3](-) 6d(2), [PaCp'3](-) 5f(2)6d(1), [UCp'3](-) 5f(3)6d(1), [NpCp'3](-) 5f(5), [PuCp'3](-) 5f(6), and [AmCp'3](-) 5f(7), respectively, according to the MO analysis. The total bonding energy decreases from the Th- to the Am-complex and the electrostatic interactions mainly dominate the bonding between the actinide atom and ligands. The electron affinity analysis suggests that the reduction reaction of AnCp'3→ [AnCp'3](-) should become increasingly facile across the actinide series from Th to Am, in accord with the known An(iii/ii) reduction potentials. This work expands the knowledge on the low oxidation state chemistry of actinides, and further motivates and guides the synthesis of related low oxidation state compounds of 5f elements.

13.
Eur Rev Med Pharmacol Sci ; 19(11): 2105-11, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26125275

RESUMO

OBJECTIVE: RLIP (Ral-interacting protein)-76/RalBP11 (Ral-binding protein-1), a multifunctional protein and stress-inducible non-ABC transporter, have been proven to serve as a critical role in cancer development and progression; however, little is known about the pathological role of RLIP76 in breast cancer patients. The study aimed to determine the correlation between RLIP76 expression in breast cancer patient and clinical outcomes. PATIENTS AND METHODS: Using RT-PCR and Western blot, messenger RNA (mRNA) and protein expression of RLIP76 were determined in breast cancer and adjacent normal mammary tissues. The relationship of RLIP76 expression with clinical characteristics of 245 breast cancer patients was analyzed by immunohistochemistry. RESULTS: In the present study, our results indicated that RLIP76 mRNA and protein were highly expressed in the breast cancer tissues while compared with adjacent normal mammary tissues and the correlation with RLIP76 protein expression was significantly associated with age (the non-ABC transporter, stage and the expression were significantly associated-T2 vs. T3-T4, p < 0.01), lymph node metastasis (N0-N1 vs. N2-N3, p < 0.01), and PR (positive vs. negative, p < 0.01) in breast cancer patients; furthermore, we also found that RLIP76 protein overexpression was an unfavorable prognostic factor in the patients suffered from breast cancer. CONCLUSIONS: RLIP76 overexpression serves as an unfavorable prognostic biomarker in breast cancer patients.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Biomarcadores Tumorais , Neoplasias da Mama/patologia , Proteínas Ativadoras de GTPase/genética , Expressão Gênica/genética , Adulto , Mama/patologia , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/metabolismo
14.
Cell Death Dis ; 5: e1190, 2014 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-24763047

RESUMO

Oplopantriol-A (OPT) is a natural polyyne from Oplopanax horridus. We show here that OPT preferentially kills cancer cells and inhibits tumor growth. We demonstrate that OPT-induced cancer cell death is mediated by excessive endoplasmic reticulum (ER) stress. Decreasing the level of ER stress either by inactivating components of the unfolded protein response (UPR) pathway or by expression of ER chaperone protein glucose-regulated protein 78 (GRP78) decreases OPT-induced cell death. We show that OPT induces the accumulation of ubiquitinated proteins and the stabilization of unstable proteins, suggesting that OPT functions, at least in part, through interfering with the ubiquitin/proteasome pathway. In support of this, inhibition of protein synthesis significantly decreased the accumulation of ubiquitinated proteins, which is correlated with significantly decreased OPT-induced ER stress and cell death. Finally, we show that OPT treatment significantly induced the expression of BH3-only proteins, Noxa and Bim. Knockdown of both Noxa and Bim significantly blocked OPT-induced cell death. Taken together, our results suggest that OPT is a potential new anticancer agent that induces cancer cell death through inducing ER stress and BH3 proteins Noxa and Bim.


Assuntos
Antineoplásicos/farmacologia , Proteínas Reguladoras de Apoptose/metabolismo , Apoptose/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Poli-Inos/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Animais , Autofagia/efeitos dos fármacos , Proteína 11 Semelhante a Bcl-2 , Linhagem Celular Tumoral , Chaperona BiP do Retículo Endoplasmático , Feminino , Técnicas de Silenciamento de Genes , Humanos , Camundongos Nus , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas Ubiquitinadas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Insect Mol Biol ; 23(3): 330-40, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24580848

RESUMO

In the present study, we identified two aldehyde reductase activities in the antennae of Helicoverpa species, NADH and NADPH-dependent activity. We expressed one of these proteins of H. armigera, aldo-keto reductase (AKR), which bears 56% identity to bovine aldose reductase, displays a NADPH-dependent activity and is mainly expressed in the antennae of adults. Whole-mount immunostaining showed that the enzyme is concentrated in the cells at the base of chemosensilla and in the nerves. The enzyme activity of H. armigera AKR is markedly different from those of mammalian enzymes. The best substrates are linear aliphatic aldehydes of 8-10 carbon atoms, but not hydroxyaldehydes. Both pheromone components of H. armigera, which are unsaturated aldehydes of 16 carbons, are very poor substrates. Unlike mammalian AKRs, the H. armigera enzyme is weakly affected by common inhibitors and exhibits a different behaviour from the action of thiols. A model of the enzyme suggests that the four cysteines are in their reduced form, as are the seven cysteines of mammalian enzymes. The occurrence of orthologous proteins in other insect species, that do not use aldehydes as pheromones, excludes the possibility of classifying this enzyme among the pheromone-degrading enzymes, as has been previously described in other insect species.


Assuntos
Antenas de Artrópodes/enzimologia , Mariposas/enzimologia , Aldeído Redutase/isolamento & purificação , Aldeídos , Aldo-Ceto Redutases , Animais , Tecido Nervoso , Feromônios/metabolismo , Sensilas
16.
Cell Death Dis ; 3: e376, 2012 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-22914324

RESUMO

Falcarindiol (FAD) is a natural polyyne with various beneficial biological activities. We show here that FAD preferentially kills colon cancer cells but not normal colon epithelial cells. Furthermore, FAD inhibits tumor growth in a xenograft tumor model and exhibits strong synergistic killing of cancer cells with 5-fluorouracil, an approved cancer chemotherapeutic drug. We demonstrate that FAD-induced cell death is mediated by induction of endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR). Decreasing the level of ER stress, either by overexpressing the ER chaperone protein glucose-regulated protein 78 (GRP78) or by knockout of components of the UPR pathway, reduces FAD-induced apoptosis. In contrast, increasing the level of ER stress by knocking down GRP78 potentiates FAD-induced apoptosis. Finally, FAD-induced ER stress and apoptosis is correlated with the accumulation of ubiquitinated proteins, suggesting that FAD functions at least in part by interfering with proteasome function, leading to the accumulation of unfolded protein and induction of ER stress. Consistent with this, inhibition of protein synthesis by cycloheximide significantly decreases the accumulation of ubiquitinated proteins and blocks FAD-induced ER stress and cell death. Taken together, our study shows that FAD is a potential new anticancer agent that exerts its activity through inducing ER stress and apoptosis.


Assuntos
Antineoplásicos Fitogênicos/toxicidade , Apoptose/efeitos dos fármacos , Di-Inos/toxicidade , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Álcoois Graxos/toxicidade , Animais , Antineoplásicos Fitogênicos/uso terapêutico , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Di-Inos/uso terapêutico , Sinergismo Farmacológico , Chaperona BiP do Retículo Endoplasmático , Álcoois Graxos/uso terapêutico , Fluoruracila/toxicidade , Células HCT116 , Proteínas de Choque Térmico/antagonistas & inibidores , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Camundongos , Transplante Heterólogo , Ubiquitinação/efeitos dos fármacos , Resposta a Proteínas não Dobradas/efeitos dos fármacos
17.
J Appl Microbiol ; 113(6): 1352-61, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22924993

RESUMO

AIMS: Secoisolariciresinol (SECO) is increasingly recognized for potential clinical application because of its preventive effects against breast and colon cancers, atherosclerosis and diabetes, and its production through biotransformation has been attempted. However, previously reported bacteria all required stringent anaerobic culture conditions, precluding large-scale production. Here, we report the isolation and characterization of bacteria that produce SECO under less stringent anaerobic culture conditions. METHODS AND RESULTS: Using defatted flaxseed as raw material, we isolated a facultative anaerobic bacterium from human faeces that hydrolysed secoisolariciresinol diglucoside-3-hydroxy-3-methyl glutaric acid (SDG-HMGA) oligomers in flaxseed to produce SECO. Both conventional assays and 16S rRNA gene sequence analysis demonstrated its close relatedness with Bacteroides uniformis. The transformation efficiency of SDG in defatted flaxseed to SECO was more than 80% by this bacterial strain. We investigated factors that might influence fermentation, such as redox potential and pH, for large-scale fermentation of defatted flaxseed to produce SECO. CONCLUSIONS: The method to produce SECO through biotransformation of defatted flaxseed with this bacterial strain is highly efficient and economic. SIGNIFICANCE AND IMPACT OF THE STUDY: This bacterial strain can transform SDG to SECO under less stringent anaerobic culture conditions, which will greatly facilitate industry-scale production of SECO.


Assuntos
Bacteroidaceae/metabolismo , Butileno Glicóis/metabolismo , Fermentação , Linho/química , Lignanas/metabolismo , Adulto , Bacteroidaceae/genética , Bacteroidaceae/isolamento & purificação , Biotransformação , Butileno Glicóis/química , Butileno Glicóis/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Fezes/microbiologia , Feminino , Glucosídeos/metabolismo , Humanos , Hidrólise , Masculino , Filogenia , RNA Ribossômico 16S/genética , Adulto Jovem
18.
J Phys Condens Matter ; 23(26): 265002, 2011 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-21642752

RESUMO

We use scanning tunneling microscopy to measure densities and characteristics of Ag islands that form on the (√3 × âˆš3)R30°-Ag phase on Si(111), as a function of deposition temperature. Nucleation theory predicts that the logarithm of island density varies linearly with inverse deposition temperature. The data show two linear regimes. At 50-125 K, islands are relatively small, and island density decreases only slightly with increasing temperature. At 180-250 K, islands are larger and polycrystalline, and island density decreases strongly with increasing temperature. At 300 K, Ag atoms can travel for distances of the order of 1 µm. Assuming that Ag diffusion occurs via thermally activated motion of single atoms between adjacent sites, the data can be explained as follows. At 50-125 K, the island density does not follow conventional Arrhenius scaling due to limited mobility and a consequent breakdown of the steady-state condition for the adatom density. At ∼ 115-125 K, a transition to conventional Arrhenius scaling with critical nucleus size (i = 1) begins, and at 180-250 K, i > 1 prevails. The transition points indicate a diffusion barrier of 0.20-0.23 eV and a pairwise Ag-Ag bond strength of 0.14 eV. These energy values lead to an estimate of i≈3-4 in the regime 180-250 K, where island density varies strongly with temperature.

19.
J Insect Physiol ; 55(9): 788-92, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19414011

RESUMO

Behavioural and electrophysiological responsiveness to three chemically different secondary plant substances was studied in larvae of Pieris rapae L. (Lepidoptera: Pieridae). Three groups of caterpillars were studied that during their larval development were exposed to different rearing diets: an artificial diet or one of two host-plants, cabbage, Brassica oleracea, or nasturtium, Tropaeolum majus. In dual-choice leaf disc assays, caterpillars reared on cabbage were strongly deterred by the phenolic chlorogenic acid, the flavonol glycoside naringin and the alkaloid strychnine. However, behavioural plasticity was found in caterpillars reared on nasturtium or artificial diet in that these did not discriminate against chlorogenic acid. Caterpillars reared on the artificial diet were also significantly less sensitive to naringin and strychnine in the behavioural assay. Electrophysiological studies of the maxillary sensilla styloconica revealed that the deterrent neuron in the medial sensillum, but not in the lateral sensillum, of cabbage-reared caterpillars was more sensitive than the same neuron type of caterpillars reared on nasturtium or artificial diet. We conclude that (1) the diet-induced behavioural habituation to deterrents can at least partly be explained by chemosensory desensitisation of a generalist type of maxillary deterrent neuron; (2) behavioural cross-habituation to the three structurally diverse deterrent compounds can be traced back to cross-sensitivity for these compounds in the same gustatory neuron.


Assuntos
Brassica/química , Borboletas/fisiologia , Tropaeolum/química , Animais , Borboletas/crescimento & desenvolvimento , Comportamento Alimentar , Larva/crescimento & desenvolvimento , Larva/fisiologia
20.
J Asian Nat Prod Res ; 9(3-5): 399-405, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17613627

RESUMO

Four new water-soluble constituents, oblongaroside A (1), oblongar ester A (2), oblongaroside B (3), and oblongaroside C (4), were isolated along with four known compounds: 4-O-beta-D-glucopyranosyl-3-hydroxybenzalcohol (5), 7-methoxyl-4-O-beta-D-glucopyranosyl-3-hydroxybenzalcohol (6), 4-O-beta-D-glucopyranosyl-3-hydroxybenzoic acid (7), and 3,4-dihydroxybenzoic acid (8) from the leaves of Ilex oblonga. Identification of their structures was achieved by 1D and 2D NMR experiments, including (1)H-(1)H COSY, NOESY, HMQC, and HMBC methods and FAB mass spectral data.


Assuntos
Ácidos Cafeicos/isolamento & purificação , Glucosídeos/isolamento & purificação , Hidroxibenzoatos/isolamento & purificação , Ilex/química , Folhas de Planta/química , Ácidos Cafeicos/química , Glucosídeos/química , Hidroxibenzoatos/química , Espectroscopia de Ressonância Magnética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...