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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 316: 124311, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38663131

RESUMO

In this study, a set of potential quasi-intrinsic photosensitizers for two-photon photodynamic therapy (PDT) are proposed based on the unnatural 2-amino-8-(1'-ß-ᴅ-2'-deoxyribofuranosyl)-imidazo[1,2-ɑ]-1,3,5-triazin-4(8H)-one (P), which is paired with the 6-amino-5-nitro-3-(1'-ß-ᴅ-2'-deoxyribofuranosyl)-2(1H)-pyridone (Z) and can specifically recognize breast and liver cancer cells. Herein, the effects of sulfur substitution and electron-donating/electron-withdrawing groups on the photophysical properties in aqueous solution are systematically investigated. The one- and two-photon absorption spectra evidence that the modifications could result in red-shifted absorption wavelength and large two-photon absorption cross-section, which contributes to selective excitation and provides effective PDT for deep-seated tissues. To ensure the efficient triplet state population, the singlet-triplet energy gaps and spin-orbit coupling constants were examined, which is responsible for a rapid intersystem crossing rate. Furthermore, these thiobase derivatives are characterized by the long-lived T1 state and the large energy gap for radiationless transition to ensure the generation of cytotoxic singlet oxygen.

2.
Cancer Lett ; 588: 216746, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38387756

RESUMO

Helicobacter pylori (H. pylori) infection is considered to be an important factor in gastric cancer (GC). Long noncoding RNA (lncRNA) and m6A modification are involved in the occurrence and development of GC, but the role of lncRNA m6A modification in the development of GC mediated by H. pylori is still unclear. Here, we found that H. pylori infection downregulated the expression of lnc-PLCB1 through METTL14-mediated m6A modification and IRF2-mediated transcriptional regulation. Overexpression of lnc-PLCB1 inhibited the proliferation and migration of GC cells, while downregulation of lnc-PLCB1 promoted the proliferation and migration ability of GC cells. In addition, clinical analysis showed that lnc-PLCB1 is lower in GC tissues than in normal tissues. Further study found that lnc-PLCB1 reduced the protein stability of its binding protein DEAD-box helicase 21 (DDX21) and then downregulated the expression of CCND1 and Slug, thereby playing tumour suppressing role in the occurrence and development of GC. In conclusion, the METTL14/lnc-PLCB1/DDX21 axis plays an important role in H. pylori-mediated GC, and lnc-PLCB1 can be used as a new target for GC treatment.


Assuntos
Adenina , Infecções por Helicobacter , Helicobacter pylori , RNA Longo não Codificante , Neoplasias Gástricas , Humanos , Helicobacter pylori/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/patologia , Regulação para Baixo , Infecções por Helicobacter/complicações , Infecções por Helicobacter/genética , Proliferação de Células , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Fosfolipase C beta/genética , Fosfolipase C beta/metabolismo , Metiltransferases/genética , Metiltransferases/metabolismo
3.
Spectrochim Acta A Mol Biomol Spectrosc ; 296: 122691, 2023 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-37023654

RESUMO

DNA alkylation is caused by long-term exposure of cells to the environmental and endogenous alkylating agents, which can also lead to DNA mutations and therefore trigger some cancers. Since O4-methylthymidine (O4-meT), mismatched with guanine (G), is the most common but not easily repaired alkylated nucleoside, monitoring O4-meT can help to effectively reduce the occurrence of carcinogenesis. In this work, the modified G-analogues are selected as the fluorescence probe to monitor the existence of O4-meT according to its pairing characteristics. The photo-physical properties of considered G-analogues formed by ring expansion or addition of fluorophores were studied in detail. It is found that, compared with natural G, the absorption peaks of these fluorescence analogues are red-shifted (>55 nm) and the luminescence is enhanced by π-conjugation. Especially, the xG has a large Stokes shift (65 nm) with fluorescence insensitive to natural cytosine (C) and retains efficient emission after pairing, while it is sensitive to O4-meT and the quenching phenomenon occurs due to the excited state intermolecular charge transfer. Accordingly, the xG can be used as a fluorescent probe to identify the O4-meT in solution. In addition, the direct use of deoxyguanine fluorescent analogue for monitoring O4-meT was evaluated by the effects of ligating deoxyribose on absorption and fluorescence emission.


Assuntos
DNA , Nucleosídeos , Fluorescência , Timidina
4.
J Chem Inf Model ; 63(7): 2037-2046, 2023 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-36962515

RESUMO

In this work, we computationally designed a set of nitroxide diradical base pairs (rC+:rC) to propose promising magnetic building blocks for spintronic or magnetic molecular materials. C+:C12 is found to possess a considerably large antiferromagnetic-like (AFM-like) spin-coupling magnitude (J = -3286.681 cm-1) and sensitive magnetic responses to the external electric field. Especially, the presence of the Y direction field that is oriented perpendicular to intermolecular hydrogen bonds has the greatest influence on the magnetic exchange interaction (J being from -2549.578 to -4231.286 cm-1, ΔJY = 1681.708 cm-1), which could be understood by two simultaneously occurring effects. On the one hand, the external electric field in the -Y direction can regulate the charge polarization of negative and positive electrostatic potentials on C12 moiety and further facilitate the spin transport property. On the other hand, with increasing electric field strength on the -Y axis, the spin density on diradical sources diminishes and that on the coupler increases, which can lead to a homogenous spin-density distribution. The achieved understanding provides a new strategy for designing self-assembly magnetic nanomaterials or nanodevices and enhancing the AFM coupling through the assistance of external electric field.


Assuntos
Magnetismo , Óxidos de Nitrogênio , Pareamento de Bases , Eletricidade
5.
J Phys Chem A ; 126(43): 7820-7828, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36282070

RESUMO

In this work, we computationally designed a series of diradical molecules with obvious magnetic coupling properties based on newly synthesized artificial bases, 6-amino-3-(1'-ß-d-2'-deoxyribofuranosyl)-5-nitro-1H-pyridin-2-one (Z), 2-amino-8-(1'-ß-d-2'-deoxyribofuranosyl)-imidazo-[1,2a]-1,3,5-triazin-[8H]-4-one (P), 6-amino-9[(1'-ß-d-2'-deoxyribofuranosyl)-4-hydroxy-5-(hydroxymethyl)-oxolan-2-yl]-1H-purin-2-one (B), and found two methods (base pairing and nitro group rotation) of regulating the magnetic magnitude, making them become magnetic switches with promising prospects. On one hand, the modified diradical artificial base P3 possesses an excellent magnetic exchange coupling constant due to its spin density concentration on a unique spin polarization path. Because of the serious mismatch between the singly occupied molecular orbital (SOMO) and the lowest unoccupied molecular orbital (LUMO) of Z-P3 base pairing, the magnetic coupling property of the Z-P3 base pair disappears, which indicates that the base pairing can be used as an effective means to regulate the molecular magnetic coupling properties. On the other hand, the investigation shows that the rotation of the nitro group on Z has an influence on the energy gaps between the closed-shell (CS) singlet and triplet (T) states of the base pairs formed by Z-analogues and thereby the expression of magnetic coupling properties. This work can help to develop the modification strategy of the diradical base and provide theoretical guidance for the design and synthesis of magnetic coupling materials with controllable magnetic coupling properties.

6.
Spectrochim Acta A Mol Biomol Spectrosc ; 282: 121675, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-35914355

RESUMO

The 8-oxo-7,8-dihydro-2'-deoxyguanine (8-oxoG) is the representative damaged nucleoside that may increase the risk of developing diseases. Accordingly, the selective detection of 8-oxoG in DNA with minimal disturbance to the native structure is important to have an in-depth understanding of the formation mechanism and becomes an attractive tool for genomic research. To identify the DNA adduct in real-time efficiently, a series of quasi-intrinsic optical probes are performed based on the natural adenine, which has preference to form a stable base pair with 8-oxoG in the syn conformation. The calculations revealed that the A-analogues in solution could bring red-shifted absorption spectra and bright photoluminescence arisen from the additional π-conjugation by means of fluorophore modification and the ring expansion. Especially, A1 possesses large Stokes shifts and the highest fluorescence intensity in emission, which is proposed as the biosensor to monitor the optical changes in the presence and absence of the considered 8-oxoG. It is found that the fluorescence is insensitive to base pairing with thymine, while the excited state intermolecular proton transfer (ESPT) induced efficient fluorescence quenching is observed upon pairing with the 8-oxoG. To evaluate the direct usefulness of the bright adenine analogues in biological environment, we further examined the influences of linking deoxyribose on the absorption and emission, which are consistent with the experimental data.


Assuntos
Adenina , Adutos de DNA , Adenina/química , Pareamento de Bases , Guanina/química , Modelos Moleculares
7.
Phys Chem Chem Phys ; 24(17): 10356-10364, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35438101

RESUMO

In this work, a set of new potential radiation sensitizers (4-substituted Z-bases: 4XZ, X = F, Cl, Br, and I) are designed based on the artificial 6-amino-5-nitro-3-(1'-ß-D-2'-deoxyribofuranosyl)-2(1H)-pyridone (Z), which can selectively bind to breast cancer cells. The calculated electron affinities in water solution show that the halogenated Z-bases are efficient electron acceptors which possess significant electron-withdrawing characters following the order of 4XZ > Z ≫ U. To ensure the effective electron attachment induced dissociation, we constructed the energy profiles related to the X-C bond cleavage of neutral and anionic bases. The results show that the X-C bond becomes relatively weak after the electron attachment. In particular, the electron induced dehalogenations of (4BrZ)- and (4IZ)- are low-barrier and exothermic, which support a high radiosensitivity. Furthermore, we characterized the vibrational excitation effect on the dissociative electron attachment, which demonstrates that the charge distribution can be regulated by the rotation-induced structural distortion accompanied by the electron localization on the nitro group. Also examined is the influence of base pairing on the dehalogenation, which is not only conducive to the electron-driven dissociation but is also beneficial to the stabilization of related products. The current study suggests 4BrZ and 4IZ can be regarded as potential targeted radiosensitizers with possible applications in reducing the side effects in radiotherapy.


Assuntos
Elétrons , Radiossensibilizantes , Pareamento de Bases , Rotação
8.
Cell Death Dis ; 13(4): 409, 2022 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-35484118

RESUMO

Helicobacter pylori (H. pylori) is one of the main causes of gastric cancer. It has been reported that circRNAs play a vital role in the development of multiple types of cancer. However, the role of H. pylori-induced circRNAs in the development of gastric cancer has not been studied. In this study, we found that H. pylori could induce the upregulation of circMAN1A2 in AGS and BGC823 cells independent of CagA. The downregulation of circMAN1A2 could inhibit the proliferation, migration and invasion of gastric cancer cells, and circMAN1A2 could promote the progression of gastric cancer induced by H. pylori by sponging miR-1236-3p to regulate MTA2 expression. Furthermore, circMAN1A2 knockdown inhibited xenograft tumour growth in vivo, and the overexpression of circMAN1A2 was associated with the progression of gastric cancer. Hence, Helicobacter pylori induced circMAN1A2 expression to promote the carcinogenesis of gastric cancer, and circMAN1A2 might be a new potential diagnostic marker and therapeutic target for gastric cancer.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , MicroRNAs , Neoplasias Gástricas , Infecções por Helicobacter/complicações , Infecções por Helicobacter/genética , Infecções por Helicobacter/metabolismo , Helicobacter pylori/metabolismo , Histona Desacetilases/metabolismo , Humanos , MicroRNAs/metabolismo , RNA Circular/genética , Proteínas Repressoras/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo
9.
Physiol Rep ; 10(1): e15165, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35005845

RESUMO

Phosphatidylinositol 3-kinase (PI3K) signaling promotes the differentiation and proliferation of regulatory B (Breg) cells, and the lipid phosphatase phosphatase and tensin homolog deleted on chromosome 10 (PTEN) antagonizes the PI3K-Akt signaling pathway. We previously demonstrated that cardiac Akt activity is increased and that restraint stress exacerbates hypertension and both heart and adipose tissue (AT) inflammation in DS/obese rats, an animal model of metabolic syndrome (MetS). We here examined the effects of restraint stress and pharmacological inhibition of PTEN on heart and AT pathology in such rats. Nine-week-old animals were treated with the PTEN inhibitor bisperoxovanadium-pic [bpV(pic)] or vehicle in the absence or presence of restraint stress for 4 weeks. BpV(pic) treatment had no effect on body weight or fat mass but attenuated hypertension in DS/obese rats subjected to restraint stress. BpV(pic) ameliorated left ventricular (LV) inflammation, fibrosis, and diastolic dysfunction as well as AT inflammation in the stressed rats. Restraint stress reduced myocardial capillary density, and this effect was prevented by bpV(pic). In addition, bpV(pic) increased the proportions of Breg and B-1 cells as well as reduced those of CD8+ T and B-2 cells in AT of stressed rats. Our results indicate that inhibition of PTEN by bpV(pic) alleviated heart and AT inflammation in stressed rats with MetS. These positive effects of bpV(pic) are likely due, at least in part, to a reduction in blood pressure, an increase in myocardial capillary formation, and an altered distribution of immune cells in fat tissue that result from the activation of PI3K-Akt signaling.


Assuntos
Traumatismos Cardíacos , Síndrome Metabólica , Tecido Adiposo/metabolismo , Animais , Traumatismos Cardíacos/metabolismo , Traumatismos Cardíacos/patologia , Inflamação/metabolismo , Lipídeos , Síndrome Metabólica/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos
10.
Front Mol Biosci ; 8: 619027, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631788

RESUMO

Serous ovarian cancer is the most common and primary death type in ovarian cancer. In recent studies, tumor microenvironment and tumor immune infiltration significantly affect the prognosis of ovarian cancer. This study analyzed the four gene expression types of ovarian cancer in TCGA database to extract differentially expressed genes and verify the prognostic significance. Meanwhile, functional enrichment and protein interaction network analysis exposed that these genes were related to immune response and immune infiltration. Subsequently, we proved these prognostic genes in an independent data set from the GEO database. Finally, multivariate cox regression analysis revealed the prognostic significance of TAP1 and CXCL13. The genetic alteration and interaction network of these two genes were shown. Then, we established a nomogram model related to the two genes and clinical risk factors. This model performed well in Calibration plot and Decision Curve Analysis. In conclusion, we have obtained a list of genes related to the immune microenvironment with a better prognosis for serous ovarian cancer, and based on this, we have tried to establish a clinical prognosis model.

11.
Spectrochim Acta A Mol Biomol Spectrosc ; 260: 119926, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34022693

RESUMO

In this work, we computationally design a series of fluorescent purine analogues based on the 2-amino-8-(1'-ß-D-2'-deoxyribofuranosyl)-imidazo[1,2-a]-1,3,5-triazin-4(8H)-one (P) to monitor the DNA replication process with merely a minimal perturbation to the natural structure of nucleic acid. The P-modified fluorescent probes present red-shifted absorption spectra and enhanced photoluminescence due to the additional π-conjugation resulting from the fluorophore modification and the ring-expansion. Efficient fluorescence quenching of P-analogues occurs upon pairing with the complementary 6-amino-5-nitro-3-(1'-ß-D-2'-deoxyribofuranosyl)-2(1H)-pyridone (Z) due to the nonradiative relaxation from the low-lying dark excited state to the ground state of Z moiety. Especially, the P3 and the P7, which have high fluorescence intensity in both gas and liquid phases, are proposed as the sensors for studying conformational switching in the presence and absence of a complementary sequence. Also examined are the influences of hydration and the linking to deoxyribose on absorption and emission processes. Besides, the potential phosphorescence emission of these modified base pairs is taken into account by constructing the relaxed potential energy curves of S0, T1 and S1 states.


Assuntos
Replicação do DNA , Corantes Fluorescentes , Pareamento de Bases , Conformação Molecular
12.
Ann N Y Acad Sci ; 1492(1): 11-26, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33340110

RESUMO

Brown adipose tissue (BAT) is an endocrine organ that contributes to thermogenesis and energy consumption. We investigated the effects of salt loading and surgical removal of whitened interscapular BAT (iBAT) on cardiac and adipose tissue pathology in DahlS.Z-Leprfa /Leprfa (DS/obese) rats, an animal model of metabolic syndrome (MetS). DS/obese rats were subjected to surgical removal of iBAT or sham surgery at 8 weeks of age and were provided with drinking water containing or not containing 0.3% NaCl for 4 weeks beginning at 9 weeks of age. Removal of iBAT suppressed the salt-induced exacerbation of left ventricular inflammation, fibrosis, and diastolic dysfunction, but not that of hypertension development, in DS/obese rats. Salt loading attenuated adipocyte hypertrophy but enhanced inflammation in both visceral white adipose tissue (WAT) and iBAT. Although iBAT removal did not affect visceral WAT pathology in salt-loaded DS/obese rats, it attenuated the elevation of circulating interleukin-6 levels in these animals. Downregulation of uncoupling protein-1 expression in iBAT of DS/obese rats was not affected by salt loading. Our results suggest that the conversion of iBAT to WAT-like tissue contributes to a salt-induced elevation of circulating proinflammatory cytokine levels that leads to exacerbation of cardiac pathology in this model of MetS.


Assuntos
Tecido Adiposo Marrom/fisiopatologia , Síndrome Metabólica/fisiopatologia , Miocárdio/patologia , Tecido Adiposo Marrom/patologia , Tecido Adiposo Marrom/cirurgia , Animais , Citocinas/sangue , Modelos Animais de Doenças , Hipertensão/etiologia , Mediadores da Inflamação/sangue , Gordura Intra-Abdominal/patologia , Gordura Intra-Abdominal/fisiopatologia , Gordura Intra-Abdominal/cirurgia , Masculino , Síndrome Metabólica/patologia , Síndrome Metabólica/cirurgia , Mutação , Obesidade/patologia , Obesidade/fisiopatologia , Obesidade/cirurgia , Ratos , Ratos Endogâmicos Dahl , Ratos Zucker , Receptores para Leptina/genética , Receptores para Leptina/fisiologia , Cloreto de Sódio na Dieta/administração & dosagem , Disfunção Ventricular Esquerda/fisiopatologia
13.
Am J Physiol Heart Circ Physiol ; 320(1): H281-H295, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33216624

RESUMO

Prebiotics ameliorate dysbiosis and influence metabolism and the immune system, but their effects on cardiovascular complications in metabolic disorders remain largely unknown. We here investigated the effects of the soluble fiber inulin on cardiac, adipose tissue, and hepatic pathology as well as on metabolic disorders in DahlS.Z-Leprfa/Leprfa (DS/obese) rats, an animal model of metabolic syndrome (MetS). DS/obese rats and their homozygous lean (DahlS.Z-Lepr+/Lepr+, or DS/lean) littermate controls were fed a purified diet containing 5% or 20% inulin from 9 to 13 wk of age. The high-fiber diet ameliorated hypertension, left ventricular inflammation, fibrosis and diastolic dysfunction; attenuated adipose tissue inflammation and fibrosis; and alleviated the elevation of interleukin-6 levels, without affecting insulin resistance, in DS/obese rats. In addition, high fiber intake ameliorated lipid accumulation, inflammation, and fibrosis; attenuated the reduction in AMPK activity; upregulated sterol regulatory element-binding protein-1c gene expression; and increased the expression of microsomal triglyceride transfer protein gene in the liver of DS/obese rats. It also mitigated increases in total and non-high-density lipoprotein cholesterol levels but increased the triglyceride concentration in serum in these rats. None of these parameters were affected by high dietary fiber in DS/lean rats. The proportion of regulatory T cells in adipose tissue was influenced by dietary fiber but not by genotype. Our results indicate that inulin exacerbates hypertriglyceridemia but alleviates hypertension and cardiac injury as well as adipose tissue and hepatic pathology in MetS rats.NEW & NOTEWORTHY Prebiotics ameliorate dysbiosis and influence metabolism and the immune system, but their effects on cardiovascular complications in metabolic disorders remain largely unknown. Inulin ameliorated hypertension, cardiac injury, and diastolic dysfunction without affecting obesity or insulin resistance in a rat model of metabolic syndrome. The favorable cardiac effects of inulin may be related to inhibition of systemic inflammation associated with a reduction in circulating interleukin-6 levels. Additionally, inulin exacerbated hypertriglyceridemia but alleviates adipose tissue and hepatic pathology in these animals, as well as increased the number of regulatory T cells in adipose tissue.


Assuntos
Tecido Adiposo/patologia , Hipertrigliceridemia/etiologia , Inulina/toxicidade , Fígado/patologia , Síndrome Metabólica/dietoterapia , Miocárdio/patologia , Prebióticos/toxicidade , Triglicerídeos/sangue , Tecido Adiposo/imunologia , Tecido Adiposo/metabolismo , Animais , Biomarcadores/sangue , Modelos Animais de Doenças , Regulação da Expressão Gênica , Hipertrigliceridemia/sangue , Hipertrigliceridemia/genética , Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/genética , Síndrome Metabólica/patologia , Miocárdio/metabolismo , Ratos Endogâmicos Dahl , Transdução de Sinais , Linfócitos T Reguladores/imunologia , Regulação para Cima
14.
Front Chem ; 8: 605117, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33330400

RESUMO

Recently, the successful incorporation of artificial base pairs in genetics has made a significant progress in synthetic biology. The present work reports the proton transfer and photoisomerization of unnatural base pair ZP, which is synthesized from the pyrimidine analog 6-amino-5-nitro-3-(1-ß-D-2'-deoxyribo-furanosyl)-2 (1H)-pyridone (Z) and paired with its Watson-Crick complement, the purine analog 2-amino-8-(1'-ß-D-2'- deoxyribofuranosyl)-imidazo[1,2-a]-1,3,5-triazin-4(8H)-one (P). To explain the mechanism of proton transfer process, we constructed the relaxed potential energy surfaces (PESs) linking the different tautomers in both gas phase and solution. Our results show that the double proton transfer in the gas phase occurs in a concerted way both in S0 and S1 states, while the stepwise mechanism becomes more favorable in solution. The solvent effect can promote the single proton transfer, which undergoes a lower energy barrier in S1 state due to the strengthened hydrogen bond. In contrast to the excited state ultrafast deactivation process of the natural bases, there is no conical intersection between S0 and S1 states along the proton transfer coordinate to activate the decay mechanism in ZP. Of particular relevance to the photophysical properties, charge-transfer character is obviously related to the nitro rotation in S1 state. We characterized the molecular vibration effect on the electronic properties, which reveals the electronic excitation can be tuned by the rotation-induced structural distortion accompanied with the electron localization on nitro group.

15.
Nutr Diabetes ; 10(1): 28, 2020 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-32778644

RESUMO

OBJECTIVES: Evidence suggests that visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) should be considered as distinct types of white fat. Although VAT plays a key role in metabolic syndrome (MetS), the role of subcutaneous adipose tissue (SAT) has been unclear. DahlS.Z-Leprfa/Leprfa (DS/obese) rats, an animal model of MetS, develop adipocyte hypertrophy and inflammation to similar extents in SAT and VAT. We have now investigated the effects of salt loading and SAT removal on cardiac, renal, and VAT pathology in DS/obese rats. METHODS: DS/obese rats were subjected to surgical removal of inguinal SAT or sham surgery at 8 weeks of age. They were provided with a 0.3% NaCl solution as drinking water or water alone for 4 weeks from 9 weeks of age. RESULTS: Salt loading exacerbated hypertension, insulin resistance, as well as left ventricular (LV) hypertrophy, inflammation, fibrosis, and diastolic dysfunction in DS/obese rats. It also reduced both SAT and VAT mass but aggravated inflammation only in VAT. Although SAT removal did not affect LV hypertrophy in salt-loaded DS/obese rats, it attenuated hypertension, insulin resistance, and LV injury as well as restored fat mass and alleviated inflammation and the downregulation of adiponectin gene expression in VAT. In addition, whereas salt loading worsened renal injury as well as upregulated the expression of renin-angiotensin-aldosterone system-related genes in the kidney, these effects were suppressed by removal of SAT. CONCLUSIONS: SAT removal attenuated salt-induced exacerbation of MetS and LV and renal pathology in DS/obese rats. These beneficial effects of SAT removal are likely attributable, at least in part, to inhibition of both VAT and systemic inflammation.


Assuntos
Gordura Intra-Abdominal/patologia , Rim/patologia , Síndrome Metabólica/cirurgia , Miocárdio/patologia , Sódio na Dieta/administração & dosagem , Gordura Subcutânea/cirurgia , Animais , Dieta Hipossódica , Modelos Animais de Doenças , Humanos , Hipertensão/patologia , Hipertrofia Ventricular Esquerda/patologia , Resistência à Insulina , Masculino , Síndrome Metabólica/patologia , Obesidade/patologia , Obesidade/cirurgia , Ratos , Ratos Endogâmicos Dahl , Gordura Subcutânea/patologia
16.
Zhongguo Zhong Yao Za Zhi ; 45(12): 2772-2783, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32627450

RESUMO

Periplocae Cortex is a traditional Chinese medicine in China, which is mainly produced in northeast China, north China, northwest China, southwest China. In recent years, the increasing in-depth research resulted in the discovery of anti-tumor and cardiac pharmacological activities of Periplocae Cortex, which has broad application prospects. On the basis of summarizing chemical components and pharmacological effects, combined with the theoretical system of Q-marker, the quality control components of Periplocae Cortex were predicted from the aspects of the correlation between chemical composition and traditional medicinal properties, traditional efficacy, and new clinical use, plasma composition, measurable composition, storage time by analyzing literature. Among the components, periplocoside, periplocin, periplogenin, 4-methoxy salicylaldehyde showed significant activity, which provides a scientific basis for quality evaluation of Periplocae Cortex.


Assuntos
Medicamentos de Ervas Chinesas/análise , Medicina Tradicional Chinesa , Biomarcadores , China , Controle de Qualidade
17.
Food Chem ; 310: 125901, 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31816533

RESUMO

The mechanism of SlMYC2, involved in methyl jasmonate (MJ)-induced tomato fruit resistance to pathogens, was investigated. The data indicated that MJ treatment enhanced the accumulation of total phenolics and flavonoids, as well as individual phenolic acids and flavonoids, which might be caused by the increased phenylalanine ammonia-lyase and polyphenol oxidase activities, induced pathogenesis-related gene (PR) expression, ß-1,3-glucanase and chitinase activities, as well as α-tomatine, by inducing GLYCOALKALOID METABOLISM gene expression. These effects, induced by MJ, partly contributed to tomato fruit resistance to Botrytis cinerea. Nevertheless, the induction effects of MJ were almost counteracted by silence of SlMYC2, and the disease incidence and lesion diameter in MJ + SlMYC2-silenced fruit were higher than those in MJ-treated fruit. These observations are the first evidence that SlMYC2 plays vital roles in MJ-induced fruit resistance to Botrytis cinerea, possibly by regulating defence enzyme activities, SlPRs expression, α-tomatine, special phenolic acids and flavonoid compounds.


Assuntos
Acetatos/metabolismo , Botrytis/patogenicidade , Ciclopentanos/metabolismo , Oxilipinas/metabolismo , Proteínas de Plantas/genética , Solanum lycopersicum/microbiologia , Acetatos/farmacologia , Ciclopentanos/farmacologia , Resistência à Doença/fisiologia , Flavonoides/metabolismo , Frutas/efeitos dos fármacos , Frutas/microbiologia , Frutas/fisiologia , Regulação da Expressão Gênica de Plantas , Interações Hospedeiro-Patógeno , Solanum lycopersicum/efeitos dos fármacos , Solanum lycopersicum/fisiologia , Oxilipinas/farmacologia , Fenilalanina Amônia-Liase/metabolismo , Doenças das Plantas/microbiologia , Proteínas de Plantas/metabolismo , Tomatina/análogos & derivados , Tomatina/metabolismo
18.
PLoS One ; 13(7): e0199675, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30044786

RESUMO

CIP2A, cancerous inhibitor of protein phosphatase 2A, was initially recognized as an oncoprotein. Recently several studies revealed that CIP2A could function as a prognosis biomarker, however, the result remained not comprehensive, partly due to small number of patients included individually. Here we carried out a meta-analysis of published studies to assess the prognostic significance of CIP2A in solid tumors. All eligible studies were identified through searching PubMed, Embase and Web of Science database. In this meta-analysis, 22 studies involving 4,579 participants were included, and we verified that CIP2A over-expression was significantly related with poor overall survival (pooled HR = 1.844, 95% CI = 1.528-2.225, P<0.001) and short disease free survival (pooled HR = 1.808, 95% CI = 1.591-2.055, P<0.001) in solid tumors. Additionally, subgroup analysis suggested that the trend of a poor overall survival with an increased CIP2A expression was present in East-Asian and European patients, as well as in lung cancer and colorectal cancer. To sum up, CIP2A over-expression was associated with poor survival in human solid tumors and might be a predictive factor of poor prognosis.


Assuntos
Autoantígenos/genética , Biomarcadores Tumorais , Expressão Gênica , Proteínas de Membrana/genética , Neoplasias/genética , Neoplasias/mortalidade , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Razão de Chances , Prognóstico , Modelos de Riscos Proporcionais , Viés de Publicação
19.
J Agric Food Chem ; 66(12): 3110-3117, 2018 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-29528226

RESUMO

MYC2, a basic helix-loop-helix transcription factor, is a master regulator in Jasmonic acid (JA) signaling pathway. However, the functions of SlMYC2 in methyl jasmonate (MeJA)-mediated fruit chilling tolerance are far from being clearly understood. Thus, in the present work, we constructed SlMYC2-silenced tomato fruit by virus-induced gene silencing (VIGS) and investigated the function of SlMYC2 in MeJA-induced tomato fruit chilling tolerance. The results showed that MeJA treatment markedly induced the SlMYC2 expression; increased proline content, lycopene content, and antioxidant enzyme activities, including superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase; inhibited the increase of electrical conductivity and malondialdehyde content; and effectively reduced the chilling injury (CI) incidence and CI index. However, these effects of MeJA treatment were partially counteracted in SlMYC2-silenced tomato fruit, and the CI incidence and CI index in ( SlMYC2-silenced + MeJA)-treated fruit were higher than those in MeJA-treated fruit. Our results indicated that SlMYC2 might be involved in MeJA-induced chilling tolerance, possibly by ameliorating the antioxidant enzyme system of fruit and increasing proline and lycopene levels.


Assuntos
Acetatos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Ciclopentanos/metabolismo , Oxilipinas/metabolismo , Proteínas de Plantas/metabolismo , Solanum lycopersicum/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Temperatura Baixa , Frutas/genética , Frutas/crescimento & desenvolvimento , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas , Solanum lycopersicum/genética , Solanum lycopersicum/crescimento & desenvolvimento , Proteínas de Plantas/genética
20.
J Sci Food Agric ; 98(10): 3815-3822, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29352462

RESUMO

BACKGROUND: Postharvest diseases result in major losses in fruits. Tomato is susceptible to postharvest rot caused by Botrytis cinerea and is regarded as a good model system to study postharvest disease and quality deterioration in fruit. To develop a safe and effective technique to alleviate disease and maintain fruit quality, the effects of methyl salicylate (MeSA) and 1-methylcyclopropene (1-MCP) either separately or combined on quality and gray mold caused by B. cinerea in tomato fruit were investigated. RESULTS: The results showed that application of MeSA (0.05 mmol L-1 ) delayed fruit ripening and reduced gray mold. Compared with MeSA treatment, 1-MCP (0.5 µL L-1 ) effectively delayed fruit ripening. Further, MeSA combined with 1-MCP treatment was more effective in inhibiting fungal decay during storage than MeSA treatment alone. The combined treatment not only enhanced pathogenesis-related protein 1 (PR1) expression, activities of defense enzymes and total phenolic content but also inhibited the increase in electrical conductivity and malondialdehyde content. The combined treatment was also more effective in retaining firmness, color change and titratable acidity content than MeSA treatment alone. CONCLUSION: MeSA combined with 1-MCP treatment was a useful technique to maintain quality and alleviate gray mold in postharvest tomato fruit during storage. © 2018 Society of Chemical Industry.


Assuntos
Botrytis/efeitos dos fármacos , Ciclopropanos/farmacologia , Conservação de Alimentos/métodos , Conservantes de Alimentos/farmacologia , Frutas/microbiologia , Salicilatos/farmacologia , Solanum lycopersicum/química , Botrytis/fisiologia , Frutas/química , Solanum lycopersicum/microbiologia , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle
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