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1.
Cell Biochem Biophys ; 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39138797

RESUMEN

Ulcerative colitis (UC) is an idiopathic inflammatory disease. We intend to explore the mechanism of Rutin in the therapy of UC. Disease activity index (DAI) and hematoxylin-eosin staining were employed to assess therapeutic effect of Rutin on dextran sulfate sodium-stimulated mice. The proliferation was detected by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay. Oxidative stress (OS) was assessed by measuring reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD). Inflammatory factors were detected using enzyme-linked immunosorbent assay and immunofluorescence staining. mRNA and protein expressions were detected by real-time quantitative polymerase chain reaction and immunoblotting assay. Rutin decreased DAI scores and ameliorated pathological damage in UC mice with decreased levels of inflammatory factors. Rutin recovered the inhibited proliferation of fetal human colon cells caused by lipopolysaccharide. Rutin inhibited OS by reducing ROS and MDA, while enhancing SOD activity in LPS-induced fetal human colon cells. Rutin inhibited NLRP3 inflammasome in UC mice and cell model. Silencing NLRP3 enhanced the inhibitory effect of Rutin on OS in lipopolysaccharide-induced fetal human colon cells. Conversely, NLRP3 overexpression reversed the restraining role of Rutin in OS. Rutin ameliorates UC by inhibiting inflammation and OS through suppressing NLRP3 inflammasome.

2.
Biomacromolecules ; 25(6): 3840-3849, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38801711

RESUMEN

The associative phase separation of charged biomacromolecules plays a key role in many biophysical events that take place in crowded intracellular environments. Such natural polyelectrolyte complexation and phase separation often occur at nonstoichiometric charge ratios with the incorporation of bioactive proteins, which is not studied as extensively as those complexations at stoichiometric ratios. In this work, we investigated how the addition of a crowding agent (polyethylene glycol, PEG) affected the complexation between chitosan (CS) and hyaluronic acid (HA), especially at nonstoichiometric ratios, and the encapsulation of enzyme (catalase, CAT) by the colloidal complexes. The crowded environment promoted colloidal phase separation at low charge ratios, forming complexes with increased colloidal and dissolution stability, which resulted in a smaller size and polydispersity (PDI). The binding isotherms revealed that the addition of PEG greatly enhanced the ion-pairing strength (with increased ion-pairing equilibrium constant Ka from 4.92 × 104 without PEG to 1.08 × 106 with 200 g/L PEG) and switched the coacervation from endothermic to exothermic, which explained the promoted complexation and phase separation. At the stoichiometric charge ratio, the enhanced CS-HA interaction in crowded media generated a more solid-like coacervate phase with a denser network, slower chain relaxation, and higher modulus. Moreover, both crowding and complex encapsulation enhanced the activity and catalytic efficiency of CAT, represented by a 2-fold increase in catalytic efficiency (Kcat/Km) under 100 g/L PEG crowding and CS-HA complex encapsulation. This is likely due to the lower polarity in the microenvironment surrounding the enzyme molecules. By a systematic investigation of both nonstoichiometric and stoichiometric charge ratios under macromolecular crowding, this work provided new insights into the complexation between natural polyelectrolytes in a scenario closer to an intracellular environment.


Asunto(s)
Catalasa , Quitosano , Ácido Hialurónico , Polietilenglicoles , Ácido Hialurónico/química , Quitosano/química , Polietilenglicoles/química , Catalasa/química , Coloides/química
3.
J Nat Prod ; 87(2): 176-185, 2024 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-38277488

RESUMEN

Celastrol is a bioactive pentacyclic triterpenoid with promising therapeutic effects that is mainly distributed in Celastraceae plants. Although some enzymes involved in the celastrol biosynthesis pathway have been reported, many biosynthetic steps remain unknown. Herein, transcriptomics and metabolic profiles of multiple species in Celastraceae were integrated to screen for cytochrome P450s (CYPs) that are closely related to celastrol biosynthesis. The CYP716 enzyme, TwCYP716C52, was found to be able to oxidize the C-2 position of polpunonic acid, a precursor of celastrol, to form the wilforic acid C. RNAi-mediated repression of TwCYP716C52 in Tripterygium wilfordii suspension cells further confirmed its involvement in celastrol biosynthesis. The C-2 catalytic mechanisms of TwCYP716C52 were further explored by using molecular docking and site-directed mutagenesis experiments. Moreover, a modular optimization strategy was used to construct an engineered yeast to produce wilforic acid C at a titer of 5.8 mg·L-1. This study elucidates the celastrol biosynthetic pathway and provides important functional genes and sufficient precursors for further enzyme discovery.


Asunto(s)
Saccharomyces cerevisiae , Triterpenos , Saccharomyces cerevisiae/metabolismo , Simulación del Acoplamiento Molecular , Triterpenos Pentacíclicos , Triterpenos/metabolismo , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Tripterygium/genética
4.
Sensors (Basel) ; 23(17)2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37688047

RESUMEN

Moisture content is an important parameter for estimating the quality of pellet feed, which is vital in nutrition, storage, and taste. The ranges of moisture content serve as an index for factors such as safe storage and nutrition stability. A rapid and non-destructive model for the measurement of moisture content in pellet feed was developed. To achieve this, 144 samples of Caragana korshinskii pellet feed from various regions in Inner Mongolia Autonomous Region underwent separate moisture content control, measurement using standard methods, and captured their images using a hyperspectral imaging (HSI) system in the spectral range of 935.5-2539 nm. The Monte Carlo cross validation (MCCV) was used to eliminate abnormal sample data from the spectral data for better model accuracy, and a global model of moisture content was built by using partial least squares regression (PLSR) with seven preprocessing techniques and two spectral feature extraction techniques. The results showed that the regression model developed by PLSR based on second derivative (SD) and competitive adaptive reweighted sampling (CARS) resulted in better performance for moisture content. The model showed predictive abilities for moisture content with a coefficient of determination of 0.9075 and a root mean square error (RMSE) of 0.4828 for the training set; and a coefficient of determination of 0.907 and a root mean square error (RMSE) of 0.5267 for the test set; and a relative prediction error of 3.3 and the standard error of 0.307.


Asunto(s)
Caragana , Imágenes Hiperespectrales , China , Método de Montecarlo , Estado Nutricional
5.
Front Med (Lausanne) ; 10: 1139248, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37554498

RESUMEN

Purpose: This meta-analysis was exerted in assessing the anticancer efficacy and safety of nab-paclitaxel (nab-P) when combined with platinum compound agents for therapy in patients with non-small cell lung cancer (NSCLC). Method: We systematically searched the following seven electronic databases: PubMed, Cochrane Library, Web of Science, Embase, CNKI, Wan Fang, and China Science and Technology Journal Data. Randomized comparative clinical [randomized controlled clinical trial (RCT)] studies on nab-P plus platinum and carboplatin or cisplatin in combination with conventional chemotherapy agents or traditional paclitaxel were searched. Results: A total of 19 RCT studies involving 6,011 patients were analyzed. The primary outcome includes the overall response rate (ORR), overall survival (OS), and progression-free survival (PFS). The secondary outcome includes adverse events (AEs). Nab-P combined with platinum (carboplatin/cisplatin) had a better ORR [odds ratio (OR) = 1.66, 95% confidence interval (CI) (1.34, 2.05), p < 0.001] and improved PFS [hazard ratio (HR) = 0.84, 95% CI: (0.74, 0.94), p = 0.01] and OS [HR = 0.86, 95% CI: (0.78, 0.96), p = 0.008] in NSCLC patients. ORR [OR = 2.18, 95% CI: (1.07, 4.43)], PFS [HR = 0.62, 95% CI: (0.40, 0.97)], and OS [HR = 0.63, 95% CI: (0.49, 0.81)] were significantly improved among patients aged >70 years, and ORR [OR = 1.80, 95% CI: (1.20, 2.70)] and PFS [HR = 0.74, 95% CI: (0.56, 0.97)] were significantly elevated with SCC rate ≥65% in NSCLC patients (all p > 0.05). Among the adverse effects, the prevalence of neutropenia, neuralgia, and arthralgia/myalgia (≥ grade 3) compared to that of the control group. On the other hand, the prevalence of anemia and thrombocytopenia was higher in the nab-P plus platinum (carboplatin/cisplatin) compared to that of controls. It is worth noting that fatigue did not show statistical significance. Conclusion: Nab-P in combination with carboplatin/cisplatin regimen improves efficacy and tolerability in patients with NSCLC. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022288499.

6.
Nat Commun ; 14(1): 2220, 2023 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-37072400

RESUMEN

Mother plants play an important role in the control of dormancy and dispersal characters of their progeny. In Arabidopsis seed dormancy is imposed by the embryo-surrounding tissues of the endosperm and seed coat. Here we show that VERNALIZATION5/VIN3-LIKE 3 (VEL3) maintains maternal control over progeny seed dormancy by establishing an epigenetic state in the central cell that primes the depth of primary seed dormancy later established during seed maturation. VEL3 colocalises with MSI1 in the nucleolus and associates with a histone deacetylase complex. Furthermore, VEL3 preferentially associates with pericentromeric chromatin and is required for deacetylation and H3K27me3 deposition established in the central cell. The epigenetic state established by maternal VEL3 is retained in mature seeds, and controls seed dormancy in part through repression of programmed cell death-associated gene ORE1. Our data demonstrates a mechanism by which maternal control of progeny seed physiology persists post-shedding, maintaining parental control of seed behaviour.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Unión al ADN/genética , Epigénesis Genética , Regulación de la Expresión Génica de las Plantas , Germinación/genética , Histona Desacetilasas/genética , Latencia en las Plantas/genética , Semillas/genética , Factores de Transcripción/genética
8.
Chin J Nat Med ; 20(9): 691-700, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36162954

RESUMEN

Tripterygium hypoglaucum (Levl.) Hutch, a traditional Chinese medicinal herb with a long history of use, is widely distributed in China. One of its main active components, celastrol, has great potential to be developed into anti-cancer and anti-obesity drugs. Although it exhibits strong pharmacological activities, there is a lack of sustainable sources of celastrol and its derivatives, making it crucial to develop novel sources of these drugs through synthetic biology. The key step in the biosynthesis of celastrol is considered to be the cyclization of 2,3-oxidosqualene into friedelin under the catalysis of 2,3-oxidosqualene cyclases. Friedelin was speculated to be oxidized into celastrol by cytochrome P450 oxidases (CYP450s). Here, we reported a cytochrome P450 ThCYP712K1 from Tripterygium hypoglaucum (Levl.) Hutch that catalyzed the oxidation of friedelin into polpuonic acid when heterologously expressed in yeast. Through substrate supplementation and in vitro enzyme analysis, ThCYP712K1 was further proven to catalyze the oxidation of friedelin at the C-29 position to produce polpunonic acid, which is considered a vital step in the biosynthesis of celastrol, and will lay a foundation for further analysis of its biosynthetic pathway.


Asunto(s)
Fármacos Antiobesidad , Triterpenos , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Triterpenos Pentacíclicos , Escualeno/análogos & derivados , Tripterygium/metabolismo , Triterpenos/metabolismo
9.
Proc Natl Acad Sci U S A ; 119(39): e2204355119, 2022 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-36122201

RESUMEN

Winter annual life history is conferred by the requirement for vernalization to promote the floral transition and control the timing of flowering. Here we show using winter oilseed rape that flowering time is controlled by inflorescence bud dormancy in addition to vernalization. Winter warming treatments given to plants in the laboratory and field increase flower bud abscisic acid levels and delay flowering in spring. We show that the promotive effect of chilling reproductive tissues on flowering time is associated with the activity of two FLC genes specifically silenced in response to winter temperatures in developing inflorescences, coupled with activation of a BRANCHED1-dependent bud dormancy transcriptional module. We show that adequate winter chilling is required for normal inflorescence development and high yields in addition to the control of flowering time. Because warming during winter flower development is associated with yield losses at the landscape scale, our work suggests that bud dormancy activation may be important for effects of climate change on winter arable crop yields.


Asunto(s)
Brassica napus , Productos Agrícolas , Flores , Estaciones del Año , Ácido Abscísico/metabolismo , Brassica napus/crecimiento & desarrollo , Productos Agrícolas/crecimiento & desarrollo , Flores/fisiología , Regulación de la Expresión Génica de las Plantas
10.
Protein Pept Lett ; 29(7): 584-594, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35657039

RESUMEN

BACKGROUND: Osteoarthritis (OA) is an inflammatory joint disorder with high incidence rates. Long non-coding RNAs (LncRNAs) influence OA development. OBJECTIVES: In this research, we attempt to figure out the functions of lncRNA BLACAT1 in human articular chondrocyte (HAC) apoptosis and extracellular matrix (ECM) degradation in OA. METHODS: Interleukin (IL)-1ß was employed to induce HAC damage. Cell viability and apoptosis were detected, with expression patterns of lncRNA BLACAT1, miR-149-5p, and HMGCR, and levels of Caspase-3, Caspase-9, BAX, Bcl-2, COL2A1, and SOX9 determined. Then, lncRNA BLACAT1 was silenced in IL-1ß-treated HACs to analyze its role in HAC damage. The target relations of lncRNA BLACAT1 and miR-149-5p and miR-149-5p and HMGCR were verified. In addition, combined experiments were performed as a miR-149-5p inhibitor or HMGCR overexpression was injected into cells with lncRNA BLACAT1 silencing. RESULTS: In IL-1ß-treated HACs, lncRNA BLACAT1 and HMGCR were overexpressed while miR- 149-5p was poorly expressed, along with reduced cell viability, enhanced apoptosis, elevated Caspase-3 and Caspase-9 activities, increased BAX level, decreased Bcl-2 level, and declined levels of COL2A1 and SOX9, which were reversed by lncRNA BLACAT1 silencing. LncRNA BLACAT1 targeted miR-149-5p, and miR-149-5p targeted HMGCR. miR-149-5p knockout or HMGCR overexpression annulled the inhibitory role of lncRNA BLACAT1 silencing in HAC apoptosis and ECM degradation. CONCLUSION: LncRNA BLACAT1 was overexpressed in IL-1ß-treated HACs, and the lncRNA BLACAT1/miR-149-5p/HMGCR ceRNA network promoted HAC apoptosis and ECM degradation.


Asunto(s)
Osteoartritis , ARN Largo no Codificante/metabolismo , Apoptosis , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Condrocitos/metabolismo , Matriz Extracelular/metabolismo , Humanos , Hidroximetilglutaril-CoA Reductasas/metabolismo , Interleucina-1beta/metabolismo , Interleucina-1beta/farmacología , Redes y Vías Metabólicas , MicroARNs/genética , MicroARNs/metabolismo , Osteoartritis/genética , Osteoartritis/metabolismo , ARN Largo no Codificante/genética , Proteína X Asociada a bcl-2/metabolismo
11.
ACS Synth Biol ; 11(7): 2394-2404, 2022 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-35687875

RESUMEN

Panax notoginseng is one of the most famous valuable medical plants in China, and its broad application in clinical treatment has an inseparable relationship with the active molecules, ginsenosides. Ginsenosides are glycoside compounds that have varied structures for the diverse sugar chain. Although extensive work has been done, there are still unknown steps in the biosynthetic pathway of ginsenosides. Here, we screened candidate glycosyltransferase genes based on the previous genome and transcriptome data of P. notoginseng and cloned the full length of 27 UGT genes successfully. Among them, we found that PnUGT33 could catalyze different ginsenoside substrates to produce higher polarity rare ginsenosides by extending the sugar chain. We further analyzed the enzymatic kinetics and predicted the catalytic mechanism of PnUGT33 by simulating molecular docking. After that, we reconstructed the biosynthetic pathway of rare ginsenoside Rg3 and gypenoside LXXV in yeast. By combining the Golden Gate method and overexpressing the UDPG biosynthetic genes, we further improved the yield of engineering yeast strain. Finally, the shake-flask culture yield of Rg3 reached 51 mg/L and the fed-batch fermentation yield of gypenoside LXXV reached 94.5 mg/L, which was the first and highest record.


Asunto(s)
Ginsenósidos , Panax notoginseng , Panax , Ginsenósidos/genética , Ginsenósidos/metabolismo , Glicosiltransferasas/genética , Glicosiltransferasas/metabolismo , Ingeniería Metabólica/métodos , Simulación del Acoplamiento Molecular , Panax/química , Panax/genética , Panax/metabolismo , Panax notoginseng/genética , Panax notoginseng/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Saponinas , Azúcares/metabolismo , Triterpenos
12.
Oxid Med Cell Longev ; 2022: 2700000, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35419165

RESUMEN

More and more attention has been paid to the use of traditional phytochemicals. Here, we first verified the therapeutic potential of a natural bioactive compound called Hinokitiol in myocardial ischemia reperfusion injury. Hinokitiol exerts cardioprotective effect through inhibition of GSK-3ß and subsequent elimination of excessive autophagy, tuning autophagic activity in moderate extent for remedial profit in acute myocardial infarction and myocardial ischemia reperfusion injury. Overall, our study establishes Hinokitiol as a novel available interventional treatment for myocardial ischemia reperfusion injury.


Asunto(s)
Daño por Reperfusión Miocárdica , Miocitos Cardíacos , Apoptosis/fisiología , Autofagia , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Humanos , Monoterpenos , Daño por Reperfusión Miocárdica/metabolismo , Miocitos Cardíacos/metabolismo , Estrés Oxidativo , Tropolona/análogos & derivados
13.
ChemistryOpen ; 11(4): e202100301, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35363428

RESUMEN

The one-pot synthesis of 2,5-furandicarboxylic acid from 2-furoic acid with a yield of 57 % was achieved for the first time using a Pd-catalyzed bromination-hydroxycarbonylation tandem reaction in HOAc-NaOAc buffer. This synthetic protocol shows major improvements compared to previously reported methods, such as using biomass-based 2-furoic acid as low-cost raw material, one-pot synthesis without isolation of intermediate products, and no need for an acidification procedure. Experiments indicate that the involved Xantphos-modified Pd-catalyst and the buffer solution play significant promoting roles for each individual reaction whereas Br2 (as the brominating reagent) had a negative effect on the second hydroxycarbonylation step, while CO was deleterious for the first bromination step. Hence, in this practical one-pot synthesis, Br2 should be consumed in the first bromination step as fully as possible, and CO is introduced after the first bromination step has been completed.


Asunto(s)
Halogenación , Paladio , Acetatos , Ácidos Dicarboxílicos , Furanos
14.
Front Bioeng Biotechnol ; 10: 805429, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35198543

RESUMEN

Friedelin, the most rearranged pentacyclic triterpene, also exhibits remarkable pharmacological and anti-insect activities. In particular, celastrol with friedelin as the skeleton, which is derived from the medicinal plant Tripterygium wilfordii, is a promising drug due to its anticancer and antiobesity activities. Although a previous study achieved friedelin production using engineered Saccharomyces cerevisiae, strains capable of producing high-level friedelin have not been stably engineered. In this study, a combined strategy was employed with integration of endogenous pathway genes into the genome and knockout of inhibiting genes by CRISPR/Cas9 technology, which successfully engineered multiple strains. After introducing an efficient TwOSC1T502E, all strains with genetic integration (tHMG1, ERG1, ERG20, ERG9, POS5, or UPC2.1) showed a 3.0∼6.8-fold increase in friedelin production compared with strain BY4741. Through further double knockout of inhibiting genes, only strains GD1 and GD3 produced higher yields. Moreover, strains GQ1 and GQ3 with quadruple mutants (bts1; rox1; ypl062w; yjl064w) displayed similar increases. Finally, the dominant strain GQ1 with TwOSC1T502E was cultured in an optimized medium in shake flasks, and the final yield of friedelin reached 63.91 ± 2.45 mg/L, which was approximately 65-fold higher than that of the wild-type strain BY4741 and 229% higher than that in ordinary SD-His-Ura medium. It was the highest titer for friedelin production to date. Our work provides a good example for triterpenoid production in microbial cell factories and lays a solid foundation for the mining, pathway analysis, and efficient production of valuable triterpenoids with friedelin as the skeleton.

15.
Plant J ; 109(3): 555-567, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34750899

RESUMEN

Triterpenes are among the most diverse plant natural products, and their diversity is closely related to various triterpene skeletons catalyzed by different 2,3-oxidosqualene cyclases (OSCs). Celastrol, a friedelane-type triterpene with significant bioactivities, is specifically distributed in higher plants, such as Celastraceae species. Friedelin is an important precursor for the biosynthesis of celastrol, and it is synthesized through the cyclization of 2,3-oxidosqualene, with the highest number of rearrangements being catalyzed by friedelane-type triterpene cyclases. However, the molecular mechanisms underlying the catalysis of friedelin production by friedelane-type triterpene cyclases have not yet been fully elucidated. In this study, transcriptome data of four celastrol-producing plants from Celastraceae were used to identify a total of 21 putative OSCs. Through functional characterization, the friedelane-type triterpene cyclases were separately verified in the four plants. Analysis of the selection pressure showed that purifying selection acted on these OSCs, and the friedelane-type triterpene cyclases may undergo weaker selective restriction during evolution. Molecular docking and site-directed mutagenesis revealed that changes in some amino acids that are unique to friedelane-type triterpene cyclases may lead to variations in catalytic specificity or efficiency, thereby affecting the synthesis of friedelin. Our research explored the functional diversity of triterpene synthases from a multispecies perspective. It also provides some references for further research on the relative mechanisms of friedelin biosynthesis.


Asunto(s)
Celastrus/genética , Celastrus/metabolismo , Transferasas Intramoleculares/genética , Transferasas Intramoleculares/metabolismo , Triterpenos Pentacíclicos/metabolismo , Tripterygium/genética , Tripterygium/metabolismo , Vías Biosintéticas , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Plantas Medicinales/genética , Plantas Medicinales/metabolismo
16.
Mol Ther Nucleic Acids ; 26: 1336-1350, 2021 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-34853731

RESUMEN

Seminoma is the most common subtype of testicular germ cell tumor, with an increasing incidence worldwide. Clusterin (CLU) expression was found to be downregulated in testicular seminoma in our previous study. We now expanded the sample size, and further indicated that CLU expression correlates with tumor stage. Tcam-2 cell line was used to investigate the CLU function in testicular seminoma, and CLU was found to inhibit the proliferation and metastasis abilities. Besides, extracellular matrix protein COL15a1 was demonstrated as the downstream of CLU to affect the epithelial-mesenchymal transition (EMT) process via competitively binding to DDR1 with COL1A1 and inhibiting the phosphorylation of PYK2. MEF2A was found to interact with CLU and bind to the promoter of COL15a1 and so upregulate its expression. This is the first study using testicular xenografts in situ to simulate testicular seminoma metastatic and proliferative capacities. In conclusion, CLU acts as a tumor suppressor to inhibit the metastasis of testicular seminoma by interacting with MEF2A to upregulate COL15a1 and blocking the EMT process.

17.
Transl Androl Urol ; 10(8): 3317-3331, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34532256

RESUMEN

BACKGROUND: Studies over the past decade have shown that long non-coding RNAs (lncRNAs) play an essential role in the tumorigenesis and progression of kidney renal clear cell carcinoma (KIRC). Meanwhile, autophagy has been demonstrated to regulate KIRC pathogenesis and targeting therapy resistance. However, the prognostic value of autophagy-related lncRNAs in KIRC patients has not been reported before. METHODS: In this study, we obtained transcriptome data of 611 KIRC cases from the TCGA database and 258 autophagy-related mRNAs from the HADb database to identify autophagy-related lncRNAs by co-expression network. A prognostic model was then established basing on these autophagy-related lncRNAs, dividing patients into high-risk and low-risk groups. Survival analysis, clinical variables dependent receiver operating characteristic (ROC) analyses, univariate/multivariate Cox analyses, and clinical correlation analysis were performed based on risk signature with R language. Gene set enrichment analysis (GSEA) was then performed to investigate the potential mechanism of the risk signature promoting KIRC progression with GSEA software. CIBERSORT algorithm was performed to assess the impact of these lncRNAs on the infiltration of immune cells. RESULTS: A total of 17 lncRNAs were screened out and all these lncRNAs were found significantly related to KIRC patients' overall survival in subsequent survival analyses. Besides, the overall survival time in the high-risk group was much poorer than in the low-risk group. The ROC analysis revealed that the prognostic value of risk signature was better than age, gender, grade, and N stage. Univariate/multivariate analyses suggested that the risk signature was an independent predictive factor for KIRC patients. Immune and autophagy related pathways were dramatically enriched in high-risk and low-risk groups, respectively, and lncRNAs related immune cells were identified by CIBERSORT. CONCLUSIONS: In summary, our identified 17 autophagy-related lncRNAs had prognostic value for KIRC patients which may function in immunomodulation.

18.
New Phytol ; 232(3): 1311-1322, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34314512

RESUMEN

Temperature variation during seed set is an important modulator of seed dormancy and impacts the performance of crop seeds through effects on establishment rate. It remains unclear how changing temperature during maturation leads to dormancy and growth vigour differences in nondormant seedlings. Here we take advantage of the large seed size in Brassica oleracea to analyse effects of temperature on individual seed tissues. We show that warm temperature during seed maturation promotes seed germination, while removal of the endosperm from imbibed seeds abolishes temperature-driven effects on germination. We demonstrate that cool temperatures during early seed maturation lead to abscisic acid (ABA) retention specifically in the endosperm at desiccation. During this time temperature affects ABA dynamics in individual seed tissues and regulates ABA catabolism. We also show that warm-matured seeds preinduce a subset of germination-related programmes in the endosperm, whereas cold-matured seeds continue to store maturation-associated transcripts including DOG1 because of effects on mRNA degradation before quiescence, rather than because of the effect of temperature on transcription. We propose that effects of temperature on seed vigour are explained by endospermic ABA breakdown and the divergent relationships between temperature and mRNA breakdown and between temperature, seed moisture and the glass transition.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Ácido Abscísico , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Endospermo/genética , Endospermo/metabolismo , Regulación de la Expresión Génica de las Plantas , Germinación , Latencia en las Plantas/genética , ARN Mensajero/genética , Semillas/metabolismo , Temperatura
19.
Chem Asian J ; 16(17): 2504-2510, 2021 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-34258877

RESUMEN

CO2 -transformations into high value-added products have become a fascinating area in green chemistry. Herein, a Ru(III)-porphyrin catalyst (RuCl3 ⋅ 3H2 O-H2 TPP) was found highly efficient in the three-component reaction of CO2 , aliphatic amines and dichloroethane (or its derivative) for synthesis of oxazolidinones in the yields of 71∼91%. It was indicated by means of the control experiments and UV-vis spectra that CO2 was stoichiometrically activated by the involved aliphatic amine substrates to form a stable carbamate salt while 1,2-dichloroethane (or its derivative) was independently activated by the involved Ru(III)-porphyrin catalyst. The combination of CO2 -activation by aliphatic amines with 1,2-dichloroethane activation by Ru(III)-porphyrin catalyst cooperatively contributed to this successful transformation.

20.
J Biomed Nanotechnol ; 16(6): 876-884, 2020 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-33187583

RESUMEN

Colorectal cancer (CRC) is one of the most common malignant tumors in the world. Cases of colon cancer have experienced dramatic growth for the past few decades in China, while the rate of rectal cancer descends 3% every year in the West. The purpose of this study is to reveal the potential impact of miR-21-5p on the occurrence process of CRC and its connection with a close homolog of L1 (CHL1). In this study, the expression level of the miR-151-3p was found to be significantly higher in colon adenocarcinoma tissue compared with adjacent normal tissues, while the CHL1 was lower in colon adenocarcinoma tissues. The expression of miR-151-3p was inversely correlated with the expression of CHL-1, as it was confirmed with correlation analysis. miR-151-3p deregulates the expression of CHL1. CHL1 overexpression can restrain the proliferation and invasion of CRC. Tumorigenesis experiments showed that the tumor growth rate of CHL1-OV was significantly reduced in mice, and its effect could be reversed by miR-151-3p mimics. Taken together, our study may provide new insights into the potential mechanisms of progression of CRC, and may provide a theory for targeted drug therapy.


Asunto(s)
Neoplasias del Colon , MicroARNs , Animales , Moléculas de Adhesión Celular , Línea Celular Tumoral , Proliferación Celular , China , Neoplasias del Colon/genética , Humanos , Ratones , MicroARNs/genética , Invasividad Neoplásica
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