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1.
J Exp Bot ; 75(5): 1580-1600, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38035729

RESUMO

Spikelet degeneration in rice (Oryza sativa L.) is a serious physiological defect, and can be regulated by soil moisture status and phytohormones. This study investigated the possibility that brassinosteroids (BRs) in collaboration with abscisic acid (ABA) are involved in mediating the effect of soil drying during meiosis on spikelet degeneration in rice. Three rice cultivars were field grown and three irrigation regimes including well watered (WW), moderate soil drying (MD), and severe soil drying (SD) were imposed during meiosis. MD significantly decreased spikelet degeneration in comparison with WW, due mainly to the alleviation in oxidative damage via enhancing ascorbate-glutathione (AsA-GSH) cycle activity in young panicles, and SD exhibited the opposite effects. Enhanced AsA-GSH cycle strength, decreased oxidative stress, and spikelet degeneration rate were closely associated with the synergistically elevated BR and ABA levels in young panicles in MD. In contrast, low BR and excessive ABA levels led to an increase in spikelet degeneration in SD. The three cultivars exhibited the same tendencies. The intrinsic link among AsA-GSH cycle, oxidative stress, spikelet degeneration rate, and BR and ABA levels was further verified by using transgenic rice lines and chemical regulators. BRs or ABA play a unique role in regulating spikelet degeneration. Synergistically increased BR and ABA levels in MD could work together to strengthen AsA-GSH cycle activity, leading to a reduction in oxidative damage and spikelet degeneration. On the other hand, a severe imbalance between low BR and excessive ABA levels may have contributed to the opposite effects in SD.


Assuntos
Ácido Abscísico , Oryza , Brassinosteroides , Oryza/fisiologia , Solo , Meiose , Água
2.
FASEB J ; 37(9): e23145, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37584654

RESUMO

Cuproptosis, a newly discovered programmed cell death induced by copper ions, is associated with the progression and drug resistance of various tumors. Docetaxel plays a vital role as a first-line chemotherapeutic agent for advanced prostate cancer; however, most patients end up with prostate cancer progression because of inherent or acquired resistance. Herein, we examined the role of cuproptosis in the chemotherapeutic resistance of prostate cancer to docetaxel. We treated prostate cancer cell lines with elesclomol-CuCl2 , as well as with docetaxel. We performed analyses of CCK8, colony formation tests, cell cycle flow assay, transmission electron microscopy, and mTOR signaling in treated cells, and treated a xenograft prostate cancer model with elesclomol-CuCl2 and docetaxel in vivo, and performed immunohistochemistry and Western blotting analysis in treated tumors. We found that elesclomol-CuCl2 could promote cell death and enhance chemosensitivity to docetaxel. Elesclomol-CuCl2 induced cell death and inhibited the growth of prostate cancer cells relying on copper ions-induced cuproptosis, not elesclomol. In addition, dihydrolipoamide S-acetyltransferase (DLAT) was involved in cuproptosis-enhanced drug sensitivity to docetaxel. Mechanistically, upregulated DLAT by cuproptosis inhibited autophagy, promoted G2/M phase retention of cells, and enhanced the sensitivity to docetaxel chemotherapy in vitro and in vivo via the mTOR signaling pathway. Our findings demonstrated that the cuproptosis-regulated DLAT/mTOR pathway inhibited autophagy and promoted cells in G2/M phase retention, thus enhancing the chemosensitivity to docetaxel. This discovery may provide an effective therapeutic option for treating advanced prostate cancer by inhibiting the chemotherapeutic resistance to docetaxel.


Assuntos
Cobre , Neoplasias da Próstata , Masculino , Humanos , Docetaxel/farmacologia , Docetaxel/uso terapêutico , Di-Hidrolipoil-Lisina-Resíduo Acetiltransferase/farmacologia , Cobre/farmacologia , Taxoides/farmacologia , Taxoides/uso terapêutico , Neoplasias da Próstata/metabolismo , Serina-Treonina Quinases TOR , Apoptose , Autofagia , Linhagem Celular Tumoral
3.
Circ Res ; 131(6): 492-506, 2022 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-35950704

RESUMO

BACKGROUND: Preeclampsia is one of the leading causes of maternal and perinatal morbidity and is characterized by hypertension, inflammation, and placental dysfunction. Gut microbiota plays key roles in inflammation and hypertension. However, its roles and mechanisms in preeclampsia have not been fully elucidated. METHODS: 16S rRNA gene sequencing and targeted metabolomics were conducted on stool samples from 92 preeclamptic patients and 86 normal late-pregnant women. Then, fecal microbiota transplantation and in vitro and in vivo functional experiments were performed to explore the roles and mechanisms of gut microbiota in preeclampsia development. RESULTS: We revealed the gut microbiota dysbiosis in preeclamptic patients, including significant reductions in short-chain fatty acid-producing bacteria and short-chain fatty acids. The gut microbiota of preeclamptic patients significantly exacerbated pathologies and symptoms of preeclamptic rats, whereas the gut microbiota of healthy pregnant women had significant protective effects. Akkermansia muciniphila, propionate, or butyrate significantly alleviated the symptoms of preeclamptic rats. Mechanistically, they significantly promoted autophagy and M2 polarization of macrophages in placental bed, thereby suppressing inflammation. Propionate also significantly promoted trophoblast invasion, thereby improved spiral arterial remodeling. Additionally, we identified a marker set consisting of Akkermansia, Oscillibacter, and short-chain fatty acids that could accurately diagnose preeclampsia. CONCLUSIONS: Our study revealed that gut microbiota dysbiosis is an important etiology of preeclampsia. Gut microbiota and their active metabolites have great potential for the treatment and diagnosis of preeclampsia. Our findings enrich the gut-placenta axis theory and contribute to the development of microecological products for preeclampsia.


Assuntos
Hipertensão , Pré-Eclâmpsia , Animais , Disbiose/microbiologia , Ácidos Graxos Voláteis/metabolismo , Feminino , Humanos , Inflamação/complicações , Macrófagos/metabolismo , Placenta/metabolismo , Gravidez , Propionatos , RNA Ribossômico 16S/genética , Ratos , Trofoblastos/metabolismo
4.
Plant Cell Environ ; 46(4): 1340-1362, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36097648

RESUMO

This study tested the hypothesis that brassinosteroids (BRs) mediate moderate soil-drying (MD) to alleviate spikelet degeneration under high temperature (HT) stress during meiosis of rice (Oryza sativa L.). A rice cultivar was pot-grown and subjected to normal temperature (NT) and HT treatments during meiosis, and two irrigation regimes including well-watered (WW) and MD were imposed to the plants simultaneously. The MD effectively alleviated the spikelet degeneration and yield loss under HT stress mainly via improving root activity and canopy and panicle traits including higher photosynthetic capacity, tricarboxylic acid cycle activity, and antioxidant capacity than WW. These parameters were regulated by BRs levels in plants. The decrease in BRs levels at HT was due mainly to the enhanced BRs decomposition, and the MD could rescue the BRs deficiency at HT via enhancing BRs biosynthesis and impeding decomposition. The connection between BRs and HT was verified by using rice BRs-deficient mutants, transgenic rice lines, and chemical regulators. Similar results were obtained in the open-air field experiment. The results suggest that BRs can mediate the MD to alleviate spikelet degeneration under HT stress during meiosis mainly via enhancing root activity, canopy traits, and young panicle traits of rice.


Assuntos
Brassinosteroides , Oryza , Brassinosteroides/farmacologia , Temperatura , Solo , Meiose
5.
FASEB J ; 36(2): e22163, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35061326

RESUMO

Early clinical studies indicated that estrogen receptor beta (ERß) might play key roles to impact the progression of clear cell renal cell carcinoma (ccRCC). The detailed molecular mechanisms, however, remain unclear. Here, we found ERß could increase the cancer stem cell (CSC) population via altering the circPHACTR4/miR-34b-5p/c-Myc signaling. Mechanism dissection revealed that ERß could suppress circular RNA PHACTR4 (circPHACTR4) expression via direct binding to the estrogen response elements (EREs) on the 5' promoter region of its host gene, phosphatase and actin regulator 4 (PHACTR4) to decrease miR-34b-5p expression. The decreased miRNA-34b-5p could then increase c-Myc mRNA translation via targeting its 3' untranslated region (3' UTR). The in vivo mouse model with subcutaneous xenografts of ccRCC cells also validated the in vitro data. Importantly, analysis results from ccRCC TCGA database and our clinical data further confirmed the above in vitro/in vivo data. Together, these results suggest that ERß may increase CSC population in ccRCC via altering ERß/circPHACTR4/miR-34b-5p/c-Myc signaling and that targeting this newly identified signal pathway may help physicians to better suppress ccRCC progression.


Assuntos
Carcinoma de Células Renais/genética , Proteínas do Citoesqueleto/genética , Receptor beta de Estrogênio/genética , Neoplasias Renais/genética , Células-Tronco Neoplásicas/patologia , Proteínas Proto-Oncogênicas c-myc/genética , RNA Circular/genética , Regiões 3' não Traduzidas/genética , Animais , Linhagem Celular , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Células HEK293 , Humanos , Camundongos Endogâmicos BALB C , MicroRNAs/genética , Fenótipo , Subunidades Proteicas/genética , Transdução de Sinais/genética
6.
Chem Rec ; 23(5): e202300019, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37017486

RESUMO

5-hydroxymethylfurfural (HMF), one of the most significant biomass-derived renewable resources, has been widely utilized to create furan-based value-added chemicals such as 2,5-diformylfuran (DFF), 5-hydroxymethyl-2-furancarboxylic acid (HMFCA), 5-formyl-2-furancarboxylic acid (FFCA), and 2,5-furan dicarboxylic acid (FDCA). Indeed, DFF, HMFCA and FFCA are key intermediate products during the oxidation of HMF to FDCA. Herein, this review aims to demonstrate the recent advances in metal-catalyzed oxidation of HMF into FDCA via two different reaction routes (HMF-DFF-FFCA-FDCA and HMF-HMFCA-FFCA-FDCA). All the four furan-based compounds are comprehensively discussed by the selective oxidation of HMF. Additionally, various metal catalysts, reaction conditions, and reaction mechanisms used to obtain the four different products are systematically reviewed. It is anticipated that this review will provide related researchers with new perspectives and speed up the development of this field.

7.
Plant Biotechnol J ; 20(2): 335-349, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34582620

RESUMO

Necrotrophic fungus Rhizoctonia solani Kühn (R. solani) causes serious diseases in many crops worldwide, including rice and maize sheath blight (ShB). Crop resistance to the fungus is a quantitative trait and resistance mechanism remains largely unknown, severely hindering the progress on developing resistant varieties. In this study, we found that resistant variety YSBR1 has apparently stronger ability to suppress the expansion of R. solani than susceptible Lemont in both field and growth chamber conditions. Comparison of transcriptomic profiles shows that the photosynthetic system including chlorophyll biosynthesis is highly suppressed by R. solani in Lemont but weakly in YSBR1. YSBR1 shows higher chlorophyll content than that of Lemont, and inducing chlorophyll degradation by dark treatment significantly reduces its resistance. Furthermore, three rice mutants and one maize mutant that carry impaired chlorophyll biosynthesis all display enhanced susceptibility to R. solani. Overexpression of OsNYC3, a chlorophyll degradation gene apparently induced expression by R. solani infection, significantly enhanced ShB susceptibility in a high-yield ShB-susceptible variety '9522'. However, silencing its transcription apparently improves ShB resistance without compromising agronomic traits or yield in field tests. Interestingly, altering chlorophyll content does not affect rice resistance to blight and blast diseases, caused by biotrophic and hemi-biotrophic pathogens, respectively. Our study reveals that chlorophyll plays an important role in ShB resistance and suppressing chlorophyll degradation induced by R. solani infection apparently improves rice ShB resistance. This discovery provides a novel target for developing resistant crop to necrotrophic fungus R. solani.


Assuntos
Oryza , Clorofila , Oryza/genética , Oryza/microbiologia , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Rhizoctonia
8.
J Exp Bot ; 73(10): 3173-3188, 2022 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-35323898

RESUMO

Breeding for improved leaf photosynthesis is considered as a viable approach to increase crop yield. Whether it should be improved in combination with other traits has not been assessed critically. Based on the quantitative crop model GECROS that interconnects various traits to crop productivity, we review natural variation in relevant traits, from biochemical aspects of leaf photosynthesis to morpho-physiological crop characteristics. While large phenotypic variations (sometimes >2-fold) for leaf photosynthesis and its underlying biochemical parameters were reported, few quantitative trait loci (QTL) were identified, accounting for a small percentage of phenotypic variation. More QTL were reported for sink size (that feeds back on photosynthesis) or morpho-physiological traits (that affect canopy productivity and duration), together explaining a much greater percentage of their phenotypic variation. Traits for both photosynthetic rate and sustaining it during grain filling were strongly related to nitrogen-related traits. Much of the molecular basis of known photosynthesis QTL thus resides in genes controlling photosynthesis indirectly. Simulation using GECROS demonstrated the overwhelming importance of electron transport parameters, compared with the maximum Rubisco activity that largely determines the commonly studied light-saturated photosynthetic rate. Exploiting photosynthetic natural variation might significantly improve crop yield if nitrogen uptake, sink capacity, and other morpho-physiological traits are co-selected synergistically.


Assuntos
Fotossíntese , Melhoramento Vegetal , Nitrogênio , Fenótipo , Fotossíntese/fisiologia , Folhas de Planta/genética
9.
Cell Biol Toxicol ; 38(4): 679-697, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35072892

RESUMO

Colorectal cancer (CRC) is regarded as one of the commonest cancer types around the world. Due to the poor understanding on the causes of CRC formation and progression, this study sets out to investigate the physiological mechanisms by which Astragalus mongholicus Bunge-Curcuma aromatica Salisb. (ARCR) regulates CRC growth and metastasis, and the role in which M2 macrophage polarization plays in this process. An orthotopic-transplant model of CRC was established to evaluate the influence of ARCR on the polarization of M2 macrophage and the growth and metastasis of tumors. Next, the binding affinity among Sp1, ZFAS1, miR-153-5p, and CCR5 was identified using multiple assays. Finally, after co-culture of bone marrow-derived macrophages (BMDM) with CRC cell line CT26.WT, the cell proliferative, invasive, and migrated abilities were assessed in gain- or loss-of-function experiments. ARCR inhibited the infiltration of M2 macrophages into tumor microenvironment to suppress the CRC growth and metastasis in vivo. Additionally, ARCR inhibited the transcription of ZFAS1 by reducing Sp1 expression to repress M2 macrophage polarization. Moreover, ZFAS1 competitively binds to miR-153-3p to upregulate the CCR5 expression. Finally, ARCR suppressed the polarization of M2 macrophages to inhibit the tumor growth and tumor metastasis in CRC by mediating the Sp1/ZFAS1/miR-153-3p/CCR5 regulatory axis. Collectively, ARCR appears to suppress the CRC cell growth and metastasis by suppressing M2 macrophage polarization via Sp1/ZFAS1/miR-153-3p/CCR5 regulatory axis. 1. ARCR suppress the CRC cell growth and metastasis 2. ZFAS1 promotes CCR5 expression by competitively binding to miR-153-3p. 3. Sp1 promotes M2 macrophage polarization by activating ZFAS1 via miR-153-3p/CCR5. 4. The study unveiled a protective target against CRC.


Assuntos
Neoplasias Colorretais , Ativação de Macrófagos , Preparações de Plantas , Astragalus propinquus/química , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/patologia , Curcuma/química , Humanos , Macrófagos/metabolismo , Macrófagos/patologia , MicroRNAs/genética , Invasividade Neoplásica , Preparações de Plantas/farmacologia , RNA Longo não Codificante/genética , Receptores CCR5/metabolismo , Fator de Transcrição Sp1/metabolismo , Microambiente Tumoral
10.
Int J Mol Sci ; 23(22)2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36430147

RESUMO

The mobilization and translocation of carbohydrates and mineral nutrients from vegetative plant parts to grains are pivotal for grain filling, often involving a whole plant senescence process. Loss of greenness is a hallmark of leaf senescence. However, the relationship between crop yield and senescence has been controversial for many years. Here, in this study, the overexpression and RNA interference lines of gene of OsNYC3 (Non-Yellow Coloring 3), a chlorophyll catabolism gene, were investigated. Furthermore, exogenous phytohormones were applied, and a treatment of alternate wetting and moderate drying (AWMD) was introduced to regulate the processes of leaf senescence. The results indicated that the delayed senescence of the "STAY-GREEN" trait of rice is undesirable for the process of grain filling, and it would cause a lower ratio of grain filling and lower grain weight of inferior grains, because of unused assimilates in the stems and leaves. Through the overexpression of OsNYC3, application of exogenous chemicals of abscisic acid (ABA), and water management of AWMD, leaf photosynthesis was less influenced, a high ratio of carbohydrate assimilates was partitioned to grains other than leaves and stems as labeled by 13C, grain filling was improved, especially for inferior spikelets, and activities of starch-synthesizing enzymes were enhanced. However, application of ethephon not only accelerated leaf senescence, but also caused seed abortion and grain weight reduction. Thus, plant senescence needs to be finely adjusted in order to make a contribution to crop productivity.


Assuntos
Oryza , Oryza/metabolismo , Grão Comestível/genética , Grão Comestível/metabolismo , Ácido Abscísico/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Sementes/genética , Sementes/metabolismo
11.
J Sci Food Agric ; 102(5): 1832-1841, 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-34460951

RESUMO

BACKGROUND: Applying organic fertilizer coupled with chemical fertilizer has been widely adopted to improve crop productivity and quality and develop sustainable agriculture. However, little information is available about the effects of organic fertilizer on the grain quality of rice (Oryza sativa L.), especially nutritional quality and starch quality. In the present study, high yielding 'super' rice cultivars were grown in the field with three cultivation practices, including zero nitrogen application (0N), local high yielding practice with chemical fertilizer (T1) and T1 treatment with additional organic fertilizer (T2). RESULTS: Application of organic fertilizer synergistically improved rice production, nitrogen use efficiency, milling and appearance quality, and nutritional quality, including the contents of glutelin, essential amino acids and microelements, and also increased amylopectin and the ratio of the short chain of amylopectin, leading to a reduction in relative crystallinity, and decreased prolamin content. Application of organic fertilizer also increased the viscosity and breakdown values, whereas it decreased the pasting temperature and gelatinization enthalpy, resulting in better cooking and eating quality. CONCLUSION: Overall, application of organific fertilizer could synergistically improve nitrogen use efficiency and grain quality, including the structure and physicochemical properties of starch, contents of high value protein and amino acids, contents of microelements, and cooking and eating quality. © 2021 Society of Chemical Industry.


Assuntos
Brassica napus , Oryza , Brassica napus/metabolismo , Produção Agrícola/métodos , Fertilizantes , Nitrogênio/metabolismo , Oryza/química , Amido/química
12.
Eur J Clin Microbiol Infect Dis ; 40(3): 503-513, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32936397

RESUMO

Breast cancer is one of the most common malignant tumors in women. More than half of breast cancer patients are not menopausal at the time of diagnosis. The occurrence and development of premenopausal breast cancer are affected by many factors. Intestinal flora, especially SCFA-producing bacteria, participates in the development of various tumors, and there is a lack of in-depth research in premenopausal breast cancer patients. We used 16S rRNA gene sequencing, targeted metabolomics, and cell culture methods to analyze the changes in the intestinal flora and metabolites of premenopausal breast cancer patients. In addition, we treated breast cancer cells with significantly altered propionate and butyrate in vitro to examine their effects on cell activity. This study followed STROBE guidelines. We found that compared with healthy premenopausal women, the composition and symbiosis of intestinal flora in patients with premenopausal breast cancer changed significantly. The abundance of short-chain fatty acid (SCFA)-producing bacteria was significantly reduced, and the key SCFA-producing enzymes were also significantly reduced. Pediococcus and Desulfovibrio could distinguish premenopausal breast cancer patients from normal premenopausal women. The related propionate and butyrate had a certain ability to inhibit breast cancer cell viability in vitro. As SCFA-producing bacteria, Pediococcus and Desulfovibrio showed potential reference value for the diagnosis of premenopausal breast cancer. The ability of propionate and butyrate to inhibit breast cancer cell lines in vitro suggests that the relevant SCFA receptor may be a new target for the treatment of premenopausal breast cancer.


Assuntos
Neoplasias da Mama/microbiologia , Microbioma Gastrointestinal , Pré-Menopausa , Adulto , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Biomarcadores Tumorais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Butiratos/metabolismo , Butiratos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Ácidos Graxos Voláteis/metabolismo , Ácidos Graxos Voláteis/farmacologia , Feminino , Microbioma Gastrointestinal/genética , Humanos , Propionatos/metabolismo , Propionatos/farmacologia , RNA Ribossômico 16S/genética , Células Tumorais Cultivadas
13.
Physiol Plant ; 171(3): 416-423, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33090487

RESUMO

Rising levels of atmospheric carbon dioxide (CO2 ) could, potentially, be exploited as a means to increase seed yield and maintain food security, especially for cereal grains. Although there have been multiple cultivar trials indicating that significant yield variation occurs, the basis for these differences has not been entirely elucidated. Here, we focus on two rice cultivars that differed in field trials to their yield sensitivity to elevated CO2 : Yangdao6hao (YD6), and Wuyunjing23 (W23) to assess whether observed yield differences (YD6 > W23) were associated with concurrent changes in leaf-level characteristics. At ambient levels of CO2 , leaf net photosynthesis (A) of YD6 was compatible with that of W23. However, at elevated CO2 , A was higher for YD6 relative to W23. The stability of leaf Rubisco content, biochemical characteristics (Vc,max, and Jmax ), nitrogen enzymatic activity, and chlorophyll concentration differed significantly, with greater values observed for YD6 relative to W23 at elevated CO2 . While such results are consistent with other studies, we also demonstrate that a higher ratio of carbon sinks (seed) to carbon sources (leaf), were linked to increases in cytokinins, and slower flag leaf senescence for the YD6 relative to the W23 cultivar at elevated CO2 . While additional data for a broader genetic selection are needed, the current study suggests a link between source/sink carbon assimilation, maintenance of photosynthetic biochemistry, and slower leaf senescence for rice cultivars that show a stronger yield response to projected CO2 levels. This information, in turn, may provide suitable metrics for future CO2 selection among rice cultivars.


Assuntos
Oryza , Dióxido de Carbono , Nitrogênio , Oryza/genética , Fotossíntese , Folhas de Planta
14.
Genomics ; 112(6): 4980-4992, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32882325

RESUMO

The dysregulation of RNA binding proteins (RBPs) regulates the progression of several cancers. However, information on the overall functions of RBPs in prostate cancer (PCa) remains largely understudied. Therefore, based on the TCGA dataset, this study identified 144 differentially expressed RBPs in tumors compared to normal tissues. Subsequently, through univariate, LASSO and multivariate Cox regression analysis, 6 RBP genes among them, MSI1, MBNL2, LENG9, REXO2, RNASE1, and PABPC1L were screened as prognostic hub genes and prognostic signature was further identified. Further analysis indicated that the high-risk group was significantly associated with poor RFS, which was validated in the MSKCC cohort. Besides, patients in the high-risk group were closely associated with dysregulation of DNA damage repair pathway, copy number alteration, tumor burden mutation, and low-response to cisplatin (P < 0.001), and bicalutamide (P < 0.001). Using the Connectivity Map, we finally predicted 3 drugs including, ribavirin, carmustine, and carbenoxolone. In summary, we identified six-RBP gene signature and 3 potential drugs against PCa, which might promote the individualized treatment strategies and further improve the quality of life among PCa patients.


Assuntos
Neoplasias da Próstata/genética , Proteínas de Ligação a RNA/genética , Antineoplásicos/uso terapêutico , Intervalo Livre de Doença , Expressão Gênica , Humanos , Masculino , Mutação , Prognóstico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Proteínas de Ligação a RNA/metabolismo
15.
Zhongguo Zhong Yao Za Zhi ; 46(9): 2267-2275, 2021 May.
Artigo em Zh | MEDLINE | ID: mdl-34047130

RESUMO

Astragali Radix-Curcumae Rhizoma is a classic drug pair mainly used for the treatment of digestive tract-related inflammation and tumors, but the ratio is not fixed in clinical practice. In order to study whether the anti-tumor effect of the drug pair is diffe-rent under different ratios, orthotopic transplantation model of colon cancer was established in mice. Then the principal component analysis(PCA) and cluster analysis(CA) were used to explore the effect of different ratios of the drug pair on the tumor growth and metastasis, and select the optimal ratio of Astragali Radix-Curcumae Rhizoma for anti-colon cancer effect. After administration for 15 days, the body weight of colon cancer mice with the tumor removed, the tumor volume and the number of liver metastases were mea-sured; the pathological changes of tumor tissue and liver tissue were observed by HE staining. At the same time, Western blot method was used to detect the protein expression level of tumor growth-related indicators in tumor tissue(Ki67, HBP1, AFP) and tumor metastasis-related indicators in liver tissue(ß-catenin, E-cadherin, vimentin, p53) of the tumor-bearing mice. Subsequently, PCA and CA were used to select the optimal ratio of Astragali Radix-Curcumae Rhizoma for anti-colon cancer effect. The experimental results showed that different ratios of Astragali Radix-Curcumae Rhizoma inhibited tumor growth and metastasis to varying degrees. The ratio at 1∶1 of Astragali Radix-Curcumae Rhizoma had the best inhibitory effect on tumor growth, and the 2∶1 ratio group had the best effect on inhibiting liver metastasis and improving weighed loss. Astragali Radix-Curcumae Rhizoma significantly up-regulated the protein expression of HBP1 in tumor tissue of colon cancer mice, and significantly down-regulated the protein expression of Ki67 and AFP in tumor tissue; meanwhile, Astragali Radix-Curcumae Rhizoma significantly up-regulated the protein expression of E-cadherin in liver tissue of colon cancer mice, and significantly reduced the protein expression of ß-catenin, vimentin and p53 in liver tissue. PCA results showed that the first three groups in the Astragali Radix-Curcumae Rhizoma compatibility group that were closer to the sham operation group were in the order of 2∶1, 1∶1 and 3∶2, among which the center distance of the 2∶1 group was the shortest from the sham operation group, indicating that the ratio 2∶1 of Astragali Radix-Curcumae Rhizoma had the best intervention effect on colon cancer in mice, consistent with the commonly used clinical proportion. CA results showed that 11 groups of colon cancer mice were classified into 3 categories: Astragali Radix-Curcumae Rhizoma compatibility group, sham operation group and model group, which was consistent with the theory. The results of this study provide a basis for more effective clinical application of Astragali Radix-Curcumae Rhizoma in the treatment of colon cancer, and provide new ideas for the development of classic drug pairs.


Assuntos
Astrágalo , Neoplasias do Colo , Medicamentos de Ervas Chinesas , Animais , Neoplasias do Colo/tratamento farmacológico , Camundongos , Raízes de Plantas , Rizoma
16.
Zhongguo Zhong Yao Za Zhi ; 46(12): 3007-3015, 2021 Jun.
Artigo em Zh | MEDLINE | ID: mdl-34467690

RESUMO

Cerebral ischemia is one of the most common diseases in China, and the drug pair of Chuanxiong Rhizoma and Paeoniae Radix Rubra can intervene in cerebral ischemia to reduce the inflammatory response of cerebral ischemia and apoptosis. To reveal the intervention mechanism of Chuanxiong Rhizoma-Paeoniae Radix Rubra drug pair on cerebral ischemia systematically, computer network pharmacology technology was used in this paper to predict the target and signaling pathway of the drug pair on the intervention of cerebral ischemia, and then the molecular docking technology was used to further analyze the mechanism of the intervention. The target results were then verified by the rat cerebral ischemia model. The target network results showed that the active compounds of Chuanxiong Rhizoma-Paeoniae Radix Rubra for cerebral ischemic disease contained 30 compounds, 38 targets and 9 pathways. The main compounds included phenolic acids in Chuanxiong Rhizoma and monoterpene glycosides in Paeoniae Radix Rubra. The key targets involved mitogen-activated protein kinase 1(MAPK1), steroid receptor coactivator(SRC), epidermal growth factor receptor(EGFR), mitogen-activated protein kinase 14(MAPK14), caspase-3(CASP3), caspase-7(CASP7), estrogen receptor 1(ESR1), and mitogen-activated protein kinase 8(MAPK8), etc. The target gene functions were biased towards protein kinase activity, protein autophosphorylation, peptidyl-serine phosphorylation and protein serine/threonine kinase activity, etc. The important KEGG pathways involved Ras signaling pathway, ErbB signaling pathway and VEGF signaling pathway. Molecular docking results showed that catechin, oxypaeoniflorin, albiflorin, paeoniflorin and benzoylpaeoniflorin had strong binding ability with MAPK1, SRC, EGFR, MAPK14 and CASP7. MCAO rat experimental results showed that Chuanxiong Rhizoma-Paeoniae Radix Rubra significantly improved the cerebral ischemia injury and interstitial edema, and significantly reduced the activation of caspase-7 and the phosphorylation of ERK1/2. The Chuanxiong Rhizoma-Paeoniae Radix Rubra drug pair alleviated cerebral ischemia injury through a network model of multi-phenotype intervention by promoting cell proliferation and differentiation, reducing inflammatory factor expression, protecting nerve cells from death and figh-ting against neuronal cell apoptosis, with its action signaling pathway most related to Ras signaling pathway, ErbB signaling pathway and VEGF signaling pathway. This study provides the basis for clinical intervention of Chuanxiong Rhizoma-Paeoniae Radix Rubra drug pair on cerebral ischemia, and also provides ideas for the modernization of drug pairs.


Assuntos
Isquemia Encefálica , Medicamentos de Ervas Chinesas , Paeonia , Animais , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/genética , Infarto Cerebral , Simulação de Acoplamento Molecular , Ratos , Rizoma
17.
J Integr Plant Biol ; 61(8): 943-963, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30246370

RESUMO

Brassinosteroids (BRs) play crucial roles in many aspects of plant development. However, their function in spikelet differentiation and degeneration in rice (Oryza sativa L.) remains unclear. Here, we investigated the roles of these phytohormones in spikelet development in field-grown rice subjected to five different nitrogen (N) fertilization treatments during panicle differentiation. BR levels and expression of genes involved in BR biosynthesis and signal transduction were measured in spikelets. Pollen fertility and the number of differentiated spikelets were closely associated with 24-epicastasterone (24-epiCS) and 28-homobrassinolide (28-homoBL) levels in spikelets. Enhanced BR biosynthesis and signal transduction, in response to N treatment, enhanced spikelet differentiation, reduced spikelet degeneration, and increased grain yield. Increases in proton-pumping ATPase activity, ATP concentration, energy charge, and antioxidant system (AOS) levels were consistent with 24-epiCS and 28-homoBL concentrations. Exogenous application of 24-epiCS or 28-homoBL on young panicles induced a marked increase in endogenous 24-epiCS or 28-homoBL levels, energy charge, AOS levels, spikelet differentiation, and panicle weight. The opposite effects were observed following treatment with a BR biosynthesis inhibitor. Our findings indicate that, in rice, BRs mediate the effects of N fertilization on spikelet development and play a role in promoting spikelet development through increasing AOS levels and energy charge during panicle development.


Assuntos
Brassinosteroides/metabolismo , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Antioxidantes/metabolismo , Oryza/genética , Oryza/fisiologia , Proteínas de Plantas/genética
18.
Biochem Biophys Res Commun ; 504(4): 797-804, 2018 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-30217448

RESUMO

The prevalence of cardiomyopathy due to metabolic stress has up-regulated dramatically; nevertheless, its molecular mechanisms remain unclear. Here we suggested that transmembrane BAX inhibitor motif-containing 1 (Tmbim1) is down-regulated in the hearts of mice fed with high fat diet (HFD). We provided evidence that Tmbim1 knockout (KO) accelerated HFD-induced metabolic disorders in mice, as supported by the remarkable increase of fasting serum glucose and insulin levels. HFD-induced cardiac dysfunctions were greatly intensified by the loss of Tmbim1, along with higher levels of lactate dehydrogenase (LDH) and creatine kinase (CK) in serum. In addition, Tmbim1 deletion significantly enhanced lipid accumulation in heart of mice administrated with HFD. Furthermore, Tmbim1 knockout reinforced myocardial inflammation, evidenced by increasing the expression of pro-inflammatory cytokines (interleukin 1ß (IL-1ß), IL-6 and tumor necrosis factor-α (TNF-α)), and the activation of nuclear factor-κB (NF-κB) signaling pathway. Tmbim1 deficiency strengthened oxidative damage in hearts of HFD-fed mice, accompanied with a significant reduction of nuclear factor-erythroid 2 related factor 2 (Nrf-2) pathway. In palmitate (PA)-treated primary cardiomyocytes, Tmbim1 ablation markedly enhanced cell inflammation and oxidative stress, which were abolished by the suppression of ROS generation and NF-κB activation. Taken together, these findings suggested that Tmbim1 might be a key suppressor of metabolic stress-induced cardiomyopathy, which could be a promising target for the treatment of metabolic syndrome-triggered myocardial damage and heart failure.


Assuntos
Cardiomiopatias/etiologia , Dieta Hiperlipídica/efeitos adversos , Proteínas de Membrana/metabolismo , Miocardite/etiologia , Estresse Oxidativo/fisiologia , Animais , Cardiomiopatias/fisiopatologia , Resistência à Insulina , Masculino , Proteínas de Membrana/genética , Síndrome Metabólica/etiologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , NF-kappa B/metabolismo , Palmitatos/farmacologia
19.
J Sci Food Agric ; 98(1): 122-133, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28543034

RESUMO

BACKGROUND: The improvement of rice cultivars plays an important role in yield increase. However, little is known about the changes in starch quality and mineral elements during the improvement of rice cultivars. This study was conducted to investigate the changes in starch quality and mineral elements in japonica rice cultivars. RESULTS: Twelve typical rice cultivars, applied in the production in Jiangsu province during the last 60 years, were grown in the paddy fields. These cultivars were classified into six types according to their application times, plant types and genotypes. The nitrogen (N), phosphorus (P) and, and potassium (K) were mainly distributed in endosperm, bran and bran, respectively. Secondary and micromineral nutrients were distributed throughout grains. With the improvement of cultivars, total N contents gradually decreased, while total P, K and magnesium contents increased in grains. Total copper and zinc contents in type 80'S in grains were highest. The improvement of cultivars enhanced palatability (better gelatinisation enthalpy and amylose content), taste (better protein content) and protein quality (better protein components and essential amino acids). Correlation analysis indicated the close relationship between mineral elements and starch quality. CONCLUSION: The mineral elements and starch quality of grains during the improvement of japonica rice cultivars are improved. © 2017 Society of Chemical Industry.


Assuntos
Minerais/análise , Oryza/química , Amido/análise , Endosperma/química , Endosperma/embriologia , Endosperma/metabolismo , Magnésio/análise , Minerais/metabolismo , Nitrogênio/análise , Nitrogênio/metabolismo , Oryza/classificação , Oryza/embriologia , Oryza/metabolismo , Fósforo/análise , Fósforo/metabolismo , Potássio/análise , Potássio/metabolismo , Sementes/química , Sementes/classificação , Sementes/embriologia , Sementes/metabolismo , Amido/metabolismo
20.
Zhongguo Zhong Yao Za Zhi ; 43(7): 1484-1491, 2018 Apr.
Artigo em Zh | MEDLINE | ID: mdl-29728041

RESUMO

To evaluate the effect and mechanism of aerial parts of Salvia miltiorrhiza(SM) on high sugar-induced Drosophila melanogaster metabolic disorder model. The levels of glucose, triglyceride and protein in SM were detected; nymphosis time was recorded, and the reliability of metabolic disorder model as well as the mechanism of aerial parts of SM were evaluated based on metabonomics. The results showed that the levels of glucose and triglyceride in model group were significantly higher than those in normal control group(P<0.05). As compared with the model group, the glucose level was significantly decreased in gliclazide(GLZ) group, SM medium(SM-M) and high(SM-H) dose groups(P<0.05, P<0.01); the triglyceride level was significantly decreased in GLZ group and SM-H group(P<0.05, P<0.01). By principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA), the metabolic level of model ones was recovered to a certain degree after intervention by aerial parts of SM. Seventeen marker compounds and four major metabolic pathways were obtained by screening differential metabolites, comparing literature and retrieving the database. The aerial parts of SM may regulate glycolipid metabolism through the impact on histidine metabolism, glycerophospholipid metabolism, pentose and glucuronate interconversions, cysteine and methionine metabolism and glycerolipid metabolism. Extract from aerial parts of SM can regulate the glycolipid metabolism of D. melanogaster metabolic disorder model and make it return to normal condition. This paper provides reference for the value discovery and resource utilization of the aerial parts of S. miltiorrhiza.


Assuntos
Drosophila melanogaster , Glicolipídeos/metabolismo , Doenças Metabólicas/tratamento farmacológico , Extratos Vegetais/farmacologia , Salvia miltiorrhiza/química , Animais , Componentes Aéreos da Planta/química , Reprodutibilidade dos Testes , Açúcares
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