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1.
Chem Biodivers ; 21(6): e202400567, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38602253

RESUMEN

Five new cytochalasins, diaporchalasins A-E (1-5), together with 14 known congeners (6-19) were isolated from the endophytic fungus Diaporthe sp. BMX12, which was isolated from the branches of Aquilaria sinensis. The structures of the new compounds were elucidated by extensive spectroscopic analyses including high-resolution electron spray ionization mass spectrometry (HR-ESI-MS) and nuclear magnetic resonance (NMR). Their absolute configurations were assigned by theoretical electronic circular dichroism (ECD) calculations. Compounds 11 and 12 featuring a keto carbonyl at C-21 displayed cytotoxicity toward K562, BEL-7402, SGC-7901, A549, and HeLa cell lines with IC50 values ranging from 4.4 to 47.4 µM.


Asunto(s)
Ascomicetos , Citocalasinas , Ensayos de Selección de Medicamentos Antitumorales , Thymelaeaceae , Citocalasinas/química , Citocalasinas/farmacología , Citocalasinas/aislamiento & purificación , Humanos , Thymelaeaceae/química , Thymelaeaceae/microbiología , Ascomicetos/química , Ascomicetos/metabolismo , Línea Celular Tumoral , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Estructura Molecular , Proliferación Celular/efectos de los fármacos , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga , Conformación Molecular , Supervivencia Celular/efectos de los fármacos
2.
Int J Mol Sci ; 24(15)2023 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-37569843

RESUMEN

Continuous cropping (CC) is a common practice in agriculture, and usually causes serious economic losses due to soil degeneration, decreased crop yield and quality, and increased disease incidence, especially in medicinal plants. Continuous cropping obstacles (CCOs) are mainly due to changes in soil microbial communities, nutrient availability, and allelopathic effects. Recently, progressive studies have illustrated the molecular mechanisms of CCOs, and valid strategies to overcome them. Transcriptomic and metabolomics analyses revealed that identified DEGs (differently expressed genes) and metabolites involved in the response to CCOs are involved in various biological processes, including photosynthesis, carbon metabolism, secondary metabolite biosynthesis, and bioactive compounds. Soil improvement is an effective strategy to overcome this problem. Soil amendments can improve the microbial community by increasing the abundance of beneficial microorganisms, soil fertility, and nutrient availability. In this review, we sum up the recent status of the research on CCOs in medicinal plants, the combination of transcriptomic and metabolomics studies, and related control strategies, including uses of soil amendments, crop rotation, and intercropping. Finally, we propose future research trends for understanding CCOs, and strategies to overcome these obstacles and promote sustainable agriculture practices in medicinal plants.


Asunto(s)
Plantas Medicinales , Microbiología del Suelo , Agricultura , Suelo , Carbono
3.
Protein Expr Purif ; 194: 106078, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35272013

RESUMEN

Camellia vietnamensis Huang, which belongs to Camellia oleifera, is a traditional Chinese medicinal plant widely planted on Hainan Island. Tea saponin is an important functional component of C. vietnamensis, and squalene is the precursor substance that controls its formation. Squalene synthase (SQS: EC 2.5.1.21) synthesizes squalene from 2 molecules of farnesyl pyrophosphate (FPP). In this study, 1683 bp of the C. vietnamensis SQS gene, designated as CvSQS, was cloned and encoded 414 amino acids. Bioinformatics and phylogenetic tree analysis revealed the high homology of CvSQS with squalene synthases from other plants. For soluble proteins, the carboxy-terminal deleted CvSQS was obtained for expression in Escherichia coli Transetta (DE3), and the recombinant protein with a weight of 42.5 kDa was detected using SDS-PAGE and Western blot. After an enzymatic reaction, the presence of squalene in the product was analyzed using GC-MS detection, which indicated that CvSQS had catalytic activity. The tissue specificity of CvSQS and its presence in seeds at various ripening stages was detected by q-RT PCR. CvSQS had the highest transcriptional level in leaves, followed by seeds, roots, and flowers; the amount of CvSQS in the seeds was highest in September. The identification and functional characterization of CvSQS is essential for further studies on the regulation mechanism of tea saponin in C. vietnamensis.


Asunto(s)
Camellia , Saponinas , Camellia/genética , Camellia/metabolismo , Clonación Molecular , ADN Complementario , Farnesil Difosfato Farnesil Transferasa/química , Filogenia , Escualeno/metabolismo ,
4.
J Nat Prod ; 85(5): 1193-1200, 2022 05 27.
Artículo en Inglés | MEDLINE | ID: mdl-35512012

RESUMEN

Eight new phenethoxy derivatives, trichoasperellins A-H (1-8), were isolated from the endophytic fungus Trichoderma asperellum G10 isolated from the medicinal plant Areca catechu L. The structures of these compounds were elucidated from spectroscopic data, J-based configurational analysis, and Mosher's methods. Compounds 1-4 and 6-8 bear one or two multioxidized C7 moieties with the same carbon skeleton. The carbon skeletons of compounds 6-8 are new, all containing three moieties connected via two acetal carbons similar to those of disaccharide glycosides. Compound 4 inhibited nitric oxide production with an IC50 value of 48.3 µM, comparable to that of the positive control indomethacin (IC50, 42.3 µM).


Asunto(s)
Hypocreales , Trichoderma , Antiinflamatorios/química , Antiinflamatorios/farmacología , Areca , Carbono , Estructura Molecular , Trichoderma/química
5.
Int J Mol Sci ; 23(16)2022 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-36012624

RESUMEN

Flavonoids are secondary metabolites widely found in plants, which perform various biological activities, such as antiinflammation, antioxidation, antitumor, and so on. Camellia vietnamensis Huang, a species of oil-tea Camellia tree, is an important woody oil crop species widely planted on Hainan Island, which provides health benefits with its high antioxidant activity and abundant flavonoid content. However, very little is known about the overall molecular mechanism of flavonoid biosynthesis in C. vietnamensis Huang. In this study, methyl jasmonate (MeJA) is used as an inducer to change the content of secondary metabolites in C. vietnamensis. Then, the potential mechanisms of flavonoid biosynthesis in C. vietnamensis leaves in response to MeJA were analyzed by metabolomics and transcriptomics (RNA sequencing). The results showed that metabolome analysis detected 104 flavonoids and 74 fatty acyls which showed different expression patterns (increased or decreased expression). It was discovered by KEGG analysis that three differentially accumulated metabolites (cinnamaldehyde, kaempferol and quercitrin) were annotated in the phenylpropanoid biosynthesis (ko00940), flavonoid biosynthesis (ko00941), and flavone and flavonol biosynthesis (ko00944) pathways. In the transcriptome analysis, 35 different genes involved in the synthesis of flavonoids were identified by MapMan analysis. The key genes (PAL, 4CL, CCR, CHI, CHS, C4H, FLS) that might be involved in the formation of flavonoid were highly expressed after 2 h of MeJA treatment. This study provides new insights and data supporting the molecular mechanism underlying the metabolism and synthesis of flavonoids in C. vietnamensis under MeJA treatment.


Asunto(s)
Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Acetatos , Ciclopentanos , Flavonoides/metabolismo , Perfilación de la Expresión Génica , Metaboloma , Oxilipinas , Proteínas de Plantas/genética , Transcriptoma
6.
Int J Mol Sci ; 23(19)2022 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-36233104

RESUMEN

Drought stress is considered the main obstacle restricting Camellia vietnamensis Huang (C. vietnamensis) yield. Hainan is the southernmost distribution region of C. vietnamensis in China and experiences a drought period annually. To study the drought-stress-response mechanism of C. vietnamensis, we treated seedlings of drought-tolerant (HD1) and drought-sensitive (WH1) cultivars with PEG-6000 (PEG) to simulate drought stress and compared the physiology and transcriptome of their leaves at 0 d, 3 d and 6 d posttreatment. Under drought stress, the growth of C. vietnamensis was inhibited, the relative water content (RWC) of leaves decreased and the contents of malondialdehyde (MDA), antioxidant enzyme activities, osmotic regulatory substances and secondary metabolites increased. Compared with those of WH1, the leaf RWC, osmotic-regulation substance content (proline, soluble protein and soluble sugar) and antioxidant enzyme activity (superoxide dismutase, peroxidase and catalase) of HD1 were significantly increased, while the relative electrical conductivity and MDA content were significantly decreased. Compared with WH1, 2812, 2070 and 919, differentially expressed genes (DEGs) were detected in HD1 0 d, 3 d and 6 d posttreatment, respectively, and the number of DEGs increased with increasing treatment time. The detected DEGs are involved in the drought stress response of C. vietnamensis mainly through plant-hormone signal transduction and lignin and flavonoid biosynthesis pathways. Drought stress significantly activated the expression of several lignin and flavonoid biosynthesis genes in HD1. Moreover, total flavonoid and total polyphenol contents in HD1 were significantly increased, suggesting that the accumulation of flavonoids may be a key factor in the drought stress response of C. vietnamensis. Additionally, 191 DEGs were associated with coding transcription factors (TFs). This study provides insight into the molecular mechanism of the drought stress response of C. vietnamensis and provides a theoretical basis for the development and cultivation of new drought-resistant cultivars.


Asunto(s)
Camellia , Sequías , Antioxidantes/metabolismo , Camellia/genética , Camellia/metabolismo , Catalasa , Hormonas , Lignina , Malondialdehído/metabolismo , Polifenoles , Prolina/metabolismo , Estrés Fisiológico/genética , Azúcares , Superóxido Dismutasa/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Agua/metabolismo
7.
Molecules ; 27(20)2022 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-36296410

RESUMEN

Camellia vietnamensis Huang is an important woody oil crop in China, which has attracted much attention because of its abundant nutritional components and pharmaceutical value. Its seeds undergo a complex series of physiological and biochemical changes during maturation, with consequent alterations in metabolites. In order to investigate the endogenous metabolism of C. vietnamensis on Hainan Island during seed development, in this study, ultra-high-performance liquid tandem chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS) and multivariate statistical analysis (MSA) were used to analyze the differences in the chemical compounds of C. vietnamensis seeds among the four maturation stages. A total of 293 metabolites were identified from the methanol extract of the seeds of C. vietnamensis. Five metabolites, belonging to benzene and substituted derivatives, 5'-deoxyribonucleosides and linear 1,3-diarylpropanoids, were found in all three comparison groups, with consistently down-regulated trends. The Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that phloretin and 5'-methylthioadenosine were the differentially expressed metabolites when seeds were in the growth periods of S2 and S3, and indole and L-tryptophan were the differentially expressed metabolites when seeds were in the growth periods of S3 and S4. In addition, 34 flavonoid metabolites were detected, of which 4 were differentially expressed. It was indicated that flavonoids dynamically change during all the oil-tea camellia seed development stages. The findings provide data for the better understanding of endogenous metabolic pathways during C. vietnamensis seed development.


Asunto(s)
Camellia , Metanol , Metanol/análisis , Triptófano/análisis , Benceno , Cromatografía Líquida de Alta Presión/métodos , Semillas/química , Flavonoides/análisis , Extractos Vegetales/química , Floretina , Indoles/análisis , Desoxirribonucleósidos , Preparaciones Farmacéuticas/análisis , , Metabolómica/métodos
8.
Molecules ; 27(6)2022 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-35335153

RESUMEN

Liver damage seriously affects human health. Over 35% of cases of acute liver damage are caused by alcohol damage. Thus, finding drugs that can inhibit and effectively treat this disease is necessary. This article mainly focuses on the effect of the metabolome physical activity of active peptides in Camellia vietnamensis active peptide (CMAP) and improving liver protection. DEAE Sepharose FF ion-exchange column chromatography was used in separating and purifying crude peptides from Camellia vietnamensis Two components, A1 and A2, were obtained, and the most active A1 was selected. Sephadex G-100 gel column chromatography was used in A1 separation and purification. Three components, Al-1, Al-2, and Al-3, were obtained. Through antioxidant activity in vitro as an index of inspection, the relatively active component A1-2 was removed. Reverse-phase high-performance liquid chromatography showed that the purity of component A1-2 was 93.45%. The extracted CMAPs acted on alcoholic liver injury cells. Metabolomics studies revealed that the up-regulated metabolites were ribothymidine and xanthine; the down-regulated metabolites were hydroxyphenyllactic acid, creatinine, stearoylcarnitine, and inosine. This study provides an effective theoretical support for subsequent research.


Asunto(s)
Camellia , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Cromatografía por Intercambio Iónico/métodos , Humanos , Péptidos
9.
J Asian Nat Prod Res ; 23(11): 1030-1036, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33225746

RESUMEN

Two new compounds named epipaxilline (1) and penerpene J (2) were isolated from the marine-derived fungus Penicillium sp. KFD28. Their structures including absolute configurations were determined on the basis of spectroscopic methods and ECD analysis. Compounds 1 and 2 showed inhibitory activities against PTP1B with IC50 values of 31.5 and 9.5 µM, respectively, and compound 2 also showed inhibitory activities against TCPTP with IC50 value of 14.7 µM.


Asunto(s)
Diterpenos , Penicillium , Hongos , Indoles , Estructura Molecular
10.
Protein Expr Purif ; 163: 105454, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31301429

RESUMEN

Pogostemon cablin is an important commercial source of patchouli oil, whose main active ingredient is patchouli alcohol. This sesquiterpene is a product of the mevalonate pathway, in which 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) is the rate-limiting enzyme. In this study, P. cablin HMGCR cDNA, comprising 2209 nucleotides encoding 425 amino acid residues was isolated, and bioinformatics analysis was used to analyze the protein sequence. Based on this analysis, a C-terminal truncated variant was engineered for recombinant expression in E. coli. The 38 kDa recombinant protein was identified by SDS-PAGE, and assayed for mevalonolactone production. According to the PcHMGCR1 gene sequence alignment with other species, the HMGCR protein had obvious resemblance with other plants HMG coenzyme A reductase and had homology with other species including plants, fungi, archaebacteria and animals. The prokaryotic expression vector was constructed by restriction enzyme digestion to be transformed into E. coli to express the recombinant protein, and 38 kDa recombinant protein was identified by the SDS-PAGE. Enzymatic activity was detected using GC-MS and, as a result, mevalonolactone was detected in the in vitro reaction mixture. Differential expression analysis showed that PcHMGCR1 expressed the highest amount in roots. The research results are of great significance for further research on the molecular biosynthesis mechanism of Patchouli alcohol in P. cablin.


Asunto(s)
Hidroximetilglutaril-CoA Reductasas/genética , Pogostemon/enzimología , Animales , Clonación Molecular , ADN Complementario , Escherichia coli , Hidroximetilglutaril-CoA Reductasas/metabolismo , Ácido Mevalónico/análogos & derivados , Ácido Mevalónico/metabolismo , Pogostemon/genética , Sesquiterpenos/metabolismo
11.
J Surg Oncol ; 120(3): 508-517, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31140623

RESUMEN

BACKGROUND AND OBJECTIVES: To build nomogram incorporating potential prognostic factors for predicting survival outcomes of testicular germ cell tumors (TGCT) patients after resection of the primary tumor. METHODS: Data of TGCT patients from the Surveillance, Epidemiology, and End Results database (2010-2016) who underwent resection of the primary tumor were collected. Overall survival (OS) and cancer-specific survival (CSS) were analyzed by using Cox regression models, nomogram, Kaplan-Meier method, and log-rank test. RESULTS: We identified 7272 TGCT patients. Age at diagnosis, histology, tumor size, American Joint Committee on Cancer (AJCC) staging system, and number of metastases sites were independent prognostic factors and were integrated into nomograms. The nomograms had higher C-indexes for both OS and CSS compared with the AJCC 7th staging system (0.881 vs 0.831 and 0.895 vs 0.856, respectively). Moreover, the new stratification of risk groups based on the nomograms showed a more significant distinction between Kaplan-Meier curves for survival outcomes than the AJCC staging system. Retroperitoneal lymph node dissection was associated with statistically improved survival probability in the nomogram middle-risk group in resected TGCT patients. CONCLUSION: The novel nomogram-based staging system could provide satisfactory risk stratification and survival prediction ability beyond traditional AJCC staging systems.


Asunto(s)
Ganglios Linfáticos/cirugía , Neoplasias de Células Germinales y Embrionarias/mortalidad , Neoplasias de Células Germinales y Embrionarias/cirugía , Nomogramas , Neoplasias Testiculares/mortalidad , Neoplasias Testiculares/cirugía , Adulto , Humanos , Escisión del Ganglio Linfático/estadística & datos numéricos , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Espacio Retroperitoneal , Estudios Retrospectivos , Programa de VERF , Tasa de Supervivencia , Estados Unidos/epidemiología , Adulto Joven
12.
Andrologia ; 51(2): e13198, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30443968

RESUMEN

Recent studies have examined the impact of phosphodiesterase type 5 inhibitors (PDE5-Is) use on the risk of prostate cancer, and biochemical recurrence (BCR) in prostate cancer patients, but the results were inconsistent. A meta-analysis was conducted to assess the associations with all published studies. Databases (PubMed, Web of Science and MEDLINE) were retrieved to identify relevant studies which explored the impact of PDE5-Is use on the risk of prostate cancer, and BCR in prostate cancer patients. The summary results along with 95% confidence intervals (CIs) were calculated. Nine articles were eligible for the inclusion criteria. The pooled analysis showed that PDE5-Is use was not related to the increased risk of prostate cancer (odds ratio (OR), 0.71; 95% CI, 0.40-1.29). Moreover, PDE5-Is use was not linked to BCR risk in prostate cancer patients with erectile dysfunction (ED) following radical prostatectomy or radiation therapy (relative risk (RR), 1.09; 95% CI, 0.89-1.34). The heterogeneity test suggested moderate heterogeneity across studies. PDE5-Is use does not influence the risk of prostate cancer, and BCR in prostate cancer patients. More well-designed studies are warranted to confirm the findings of our analyses.


Asunto(s)
Recurrencia Local de Neoplasia/etiología , Inhibidores de Fosfodiesterasa 5/efectos adversos , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/etiología , Disfunción Eréctil/tratamiento farmacológico , Humanos , Masculino , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Prostatectomía , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Factores de Riesgo
13.
Zhongguo Zhong Yao Za Zhi ; 44(18): 3974-3978, 2019 Sep.
Artículo en Zh | MEDLINE | ID: mdl-31872733

RESUMEN

Callicarpa nudiflora,which is a big brand of Li nationality medicine with Hainan characteristics,has the effects of dissolving stasis,hemostasis,anti-inflammatory and antibacterial. At present,there is a lack of information about the reference genome of C. nudiflora. The study of the genome size,heterozygosity rate and characteristics of SSR of C. nudiflora,can provide an effective basis for the formulation of the whole genome de novo sequencing strategy and development of SSR molecular markers of C. nudiflora. To realize this purpose,high throughput sequencing platform Illumina Hiseq was used to sequence the genome structure of C. nudiflora and K-mer analysis was applied to estimate genome size,repeat sequences and heterozygosity rate. Simple-sequence repeat( SSR) loci that are suitable as markers were identified by MISA software. The results showed the estimated genome size of C. nudiflora was 822. 43 Mb,with a 0. 85% heterozygosity rate and 71. 67% repeats,and the GC content of genome was about 49. 20%. Therefore,C. nudiflora belongs to a complex genome with high heterozygosity and repetition. SSR molecular genetic markers were analyzed in the genome sequence,and a total of 206 049 SSRs were identified,among which mono-nucleotide,di-nucleotide and tri-nucleotide repetitive motifs summed up to 198 993,accounting for 96. 57% of the total SSRs. Among the 2-6 nucleotide repeats,AT/AT,AAT/ATT,AGCC/CTGG,AAAAT/ATTTT and AGATAT/ATATCT have the largest number,respectively. This report represents the first genome-wide characterization of C. nudiflora,and provides a reference for the construction of the library for the fine sequencing of the genome,and a molecular basis for the development of SSR molecular markers as well as for the protection and utilization of gene resources.


Asunto(s)
Callicarpa/genética , Genoma de Planta , Repeticiones de Microsatélite , Marcadores Genéticos , Polimorfismo Genético
14.
Protein Expr Purif ; 152: 13-22, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30017744

RESUMEN

A proteomic approach was used to understand the molecular mechanisms underlying obstacles to the continuous cropping of Pogostemon cablin. We examined differences in protein abundance between control (CK) and continuously cropped (TR) P. cablin leaves at different time points (90, 150, and 210 days after culture). Comparative analysis by two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS) revealed 183 differentially expressed protein spots, of which 87 proteins or isoforms were identified using mass spectrometry. Among these differentially expressed proteins (DEPs), 50 proteins or isoforms showed increased abundance and 37 proteins or isoforms showed decreased abundance in the TR sample compared with the abundance in the CK sample. Bioinformatic tools were used to analyze the DEPs. These proteins were classified into 12 categories according to clusters of orthologous groups (COG) analysis, with the majority being involved in post-translational modification, protein turnover, and chaperones, followed by carbohydrate transport and metabolism, and finally, energy production and conversion. Protein-protein interactions revealed that 18 DEPs were involved in energy metabolism, 6 DEPs were involved in stress response, and 4 DEPs were involved in amino acid biosynthesis. Continuous cropping altered the expression of proteins related to energy metabolism, carbohydrate metabolism, and amino acid metabolism in P. cablin leaves. Among these processes, the most affected was energy metabolism, which may be pivotal for resistance to continuous cropping.


Asunto(s)
Regulación de la Expresión Génica de las Plantas , Hojas de la Planta/genética , Proteínas de Plantas/genética , Pogostemon/genética , Procesamiento Proteico-Postraduccional , Proteoma/genética , Transporte Biológico/genética , Metabolismo de los Hidratos de Carbono/genética , Biología Computacional/métodos , Metabolismo Energético/genética , Ontología de Genes , Chaperonas Moleculares/clasificación , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Anotación de Secuencia Molecular , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Proteínas de Plantas/clasificación , Proteínas de Plantas/metabolismo , Pogostemon/química , Pogostemon/metabolismo , Mapeo de Interacción de Proteínas , Proteoma/clasificación , Proteoma/metabolismo
15.
J Pharmacol Exp Ther ; 357(3): 466-75, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-27048660

RESUMEN

UNLABELLED: ß-Lapachone [ß-lap; 3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b]pyran-5,6-dione] is a novel anticancer drug currently under investigation in phase I/II clinical trials. However, the mechanism underlying its clinical efficacy remains unclear. In this study, we found that ß-lap provoked the cleavage of heat shock protein 90 (Hsp90) in NAD(P)H: quinone oxidoreductase-1 (NQO1)-expressing lung and prostate cancer cells as well as in primary human umbilical vein endothelial cells (HUVECs). These actions of ß-lap were different from that of the conventional Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin. As a consequence of Hsp90 cleavage, Hsp90-associated oncoproteins, such as receptor-interacting protein, Raf-1, AKT, and CDK4, were degraded in treated cancer cells, and key receptor tyrosine kinases such as vascular endothelial cell growth factor receptor-2 and Her-2 were degraded in treated HUVECs through a proteasomal system. Further results revealed that specific inhibitors of NQO1 and reactive oxygen species could dramatically reduce ß-lap-mediated Hsp90 cleavage. In addition to its cytotoxicity, ß-lap effectively inhibited angiogenesis by suppressing tube formation and the invasion of HUVECs in vitro, rat aortic microvascular sprouts ex vivo, and mouse corneal neovascularization in vivo. Furthermore, ß-lap markedly suppressed the growth and angiogenesis of human lung cancer xenografts in nude mice and decreased the levels of receptor-interacting protein, AKT, CDK4, and CD31 in the solid tumors. Unlike other NQO1-dependent cytotoxic quinones, such as streptonigrin, menadione, mitomycin, and 17-allylamino-17-demethoxygeldanamycin, ß-lap was the only agent that could cause Hsp90 cleavage. Taken together, our results suggest a crucial mechanism underlying the antitumor efficacy of ß-lap.


Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Antineoplásicos/farmacología , Proteínas HSP90 de Choque Térmico/metabolismo , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , Naftoquinonas/farmacología , Estrés Oxidativo/efectos de los fármacos , Proteolisis/efectos de los fármacos , Inhibidores de la Angiogénesis/uso terapéutico , Animales , Antineoplásicos/uso terapéutico , Aorta/efectos de los fármacos , Aorta/fisiología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Masculino , Ratones , Naftoquinonas/uso terapéutico , Neovascularización Patológica/tratamiento farmacológico , Proteínas Oncogénicas/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Estabilidad Proteica/efectos de los fármacos , Ratas , Ensayos Antitumor por Modelo de Xenoinjerto
16.
Cancer Epidemiol ; 92: 102647, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39142240

RESUMEN

BACKGROUND: Height is associated with increased cancer risk, but most studies focus on Western populations. We aimed to evaluate this relationship in East Asians. METHOD: Observational analyses were performed utilizing data from China Kadoorie Biobank (CKB) prospective cohort. Adjusted hazard ratios (HRs) and corresponding 95 % confidence intervals (CIs) were estimated using Cox proportional hazards models. Two-sample Mendelian randomization (MR) analyses explored causal effects between height and cancer using data from Korean Genome and Epidemiology Study (KoGES), Biobank Japan (BBJ), and CKB. RESULTS: Over a median 10.1-years follow-up, 22,731 incident cancers occurred. In observational analyses, after Bonferroni correction, each 10 cm increase in height was significantly associated with higher risk of overall cancer (HR 1.16, 95 % CI 1.14-1.19, P < 0.001), lung cancer (1.18, 95 % CI 1.12-1.24, P < 0.001), esophageal cancer (1.21, 95 % CI 1.12-1.30, P < 0.001), breast cancer (1.41, 95 % CI 1.31-1.53, P < 0.001), and cervix uteri cancer (1.29, 95 % CI 1.15-1.45, P < 0.001). Each 10 cm increase in height was suggestively associated with increased risk for lymphoma (1.18, 95 % CI 1.04-1.34, P = 0.010), colorectal cancer (1.09, 95 % CI 1.02-1.16, P = 0.010), and stomach cancer (1.07, 95 % CI 1.00-1.14, P = 0.044). In MR analyses, genetically predicted height (per 1 standard deviation increase, 8.07 cm) was suggestively associated with higher risk of lung cancer (odds ratio [OR] 1.17, 95 % confidence interval [CI] 1.02-1.35, P = 0.0244) and gastric cancer (OR 1.14, 95 % CI 1.02-1.29, P = 0.0233). CONCLUSIONS: Taller height was significantly related to a higher risk for overall cancer, lung cancer, esophageal cancer, breast cancer, and cervix uteri cancer. Our findings suggest that height may be a potential causal risk factor for lung and gastric cancers among East Asians.


Asunto(s)
Estatura , Análisis de la Aleatorización Mendeliana , Neoplasias , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Asia Oriental/epidemiología , Estatura/genética , China/epidemiología , Pueblos del Este de Asia/genética , Estudios de Seguimiento , Neoplasias/epidemiología , Neoplasias/genética , Estudios Prospectivos , Factores de Riesgo
17.
Plants (Basel) ; 13(15)2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39124195

RESUMEN

Casparian strip membrane domain proteins (CASPs), regulating the formation of Casparian strips in plants, serve crucial functions in facilitating plant growth, development, and resilience to abiotic stress. However, little research has focused on the characteristics and functions of AhCASPs in cultivated peanuts. In this study, the genome-wide identification and expression analysis of the AhCASPs gene family was performed using bioinformatics and transcriptome data. Results showed that a total of 80 AhCASPs members on 20 chromosomes were identified and divided into three subclusters, which mainly localized to the cell membrane. Ka/Ks analysis revealed that most of the genes underwent purifying selection. Analysis of cis elements suggested the possible involvement of AhCASPs in hormonal and stress responses, including GA, MeJA, IAA, ABA, drought, and low temperature. Moreover, 20 different miRNAs for 37 different AhCASPs genes were identified by the psRNATarget service. Likewise, transcriptional analysis revealed key AhCASPs responding to various stresses, hormonal processing, and tissue types, including 33 genes in low temperature and drought stress and 41 genes in tissue-specific expression. These results provide an important theoretical basis for the functions of AhCASPs in growth, development, and multiple stress resistance in cultivated peanuts.

18.
Geriatr Gerontol Int ; 24(7): 675-682, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38764254

RESUMEN

AIMS: The association of sleep traits (insomnia, sleep duration, chronotype, daytime sleepiness, and snoring) with benign prostatic hyperplasia (BPH) is unclear. This research aimed to examine the effects of sleep traits on BPH risk. METHODS: A total of 170 241 men aged 38 to 73 years from UK Biobank were included. An overall healthy sleep score was created based on five sleep traits. A Cox regression model was utilized to compute adjusted hazard ratios (HRs) and population attributable fractions (PAFs) with 95% confidence intervals (CIs) for BPH risk in relation to sleep traits. RESULTS: During a median of 12.0 years follow-up, 13 026 incident BPH cases occurred. We observed that sleep duration (7-8 h/d; HR 0.95; 95% CI 0.92-0.99), no frequent insomnia (HR 0.71; 95% CI 0.69-0.74), and no frequent daytime sleepiness (HR 0.86; 95% CI 0.79-0.93) were significantly related to reduced BPH risk. Each one-point increment of the healthy sleep score was related to a decreased BPH risk, with an adjusted HR of 0.90 (95% CI 0.89-0.92). The multivariable-adjusted HR in men adopting five versus zero to one low-risk sleep traits was 0.68 (95% CI 0.61-0.75) for BPH risk. Estimates of the PAF indicated that 9.1% (95% CI 5.8-12.5%) of BPH cases would be prevented if all individuals had adopted all five low-risk sleep traits, assuming causality. CONCLUSIONS: Our study indicates an association between a healthy sleep pattern and a lower risk of BPH, emphasizing the importance of adhering to such patterns for potentially reducing BPH risk. Geriatr Gerontol Int 2024; 24: 675-682.


Asunto(s)
Hiperplasia Prostática , Humanos , Masculino , Hiperplasia Prostática/epidemiología , Hiperplasia Prostática/complicaciones , Persona de Mediana Edad , Reino Unido/epidemiología , Anciano , Estudios Prospectivos , Adulto , Sueño/fisiología , Bancos de Muestras Biológicas , Factores de Riesgo , Trastornos del Sueño-Vigilia/epidemiología , Modelos de Riesgos Proporcionales , Incidencia , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Biobanco del Reino Unido
19.
Plants (Basel) ; 13(5)2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38475531

RESUMEN

Microbial communities are an important component of mangrove ecosystems. In order to reveal the diversity of endophytic fungi in the mangrove ferns Acrostichum speciosum and A. aureum in China, the internal transcribed spacer (ITS) regions of endophytic fungi in four plant tissues (leaves, petioles, roots, and rhizomes) from three locations (Zhanjiang, Haikou, and Wenchang) were sequenced. The richness, species composition, and community similarity were analyzed. The main results are as follows: the dominant fungi in A. speciosum and A. aureum belonged to the phyla Ascomycota and Basidiomycota, accounting for more than 75% of the total identified fungi; in terms of species composition at the operational taxonomic unit (OTU) level, the endophytic fungi in A. aureum were more diverse than those in A. speciosum, and the endophytic fungi in rhizomes were more diverse than in other tissues. In Zhanjiang, both A. speciosum and A. aureum showed the richest diversity of endophytic fungi, both at the OTU classification level and in terms of species composition. Conversely, the richness of endophytic fungi in the samples of A. speciosum from Wenchang and Haikou is extremely low. The regional differences in dominant fungi increase with the degrading of taxonomic levels, and there were also significant differences in the number of unique fungi among different origins, with Zhanjiang samples having a larger number of unique fungi than the other locations. There were significant differences in the dominant fungi among different tissues, with Xylariales being the dominant fungi in rhizomes of A. speciosum and Hypocreales being the dominant fungi in the petioles, roots, and rhizomes of A. aureum. Overall, the community similarity of endophytic fungi among locations is moderately dissimilar (26-50%), while the similarity between tissues is moderately similar (51-75%). The low diversity of endophytic fungi could be one of the main reasons for the endangerment of A. speciosum. The protection of the diversity of endophytic fungi in the underground parts of A. speciosum is essential for the conservation of this critically endangered mangrove fern.

20.
Int J Biol Macromol ; 262(Pt 1): 130019, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38331077

RESUMEN

As an essential trace element for plant growth and development, manganese plays a crucial role in the uptake of the heavy metal cadmium by rice (Oryza sativa L.). In this study, we developed a novel slow-release manganese fertilizer named Mn@LNS-EL. Initially, lignin nanoparticles were derived from sodium lignosulfonate, and a one-step emulsification strategy was employed to prepare a water-in-oil-in-water (W/O/W) Pickering double emulsions. These double emulsions served as the template for interfacial polymerization of lignin nanoparticles and epichlorohydrin, resulting in the formation of microcapsule wall materials. Subsequently, manganese fertilizer (MnSO4) was successfully encapsulated within the microcapsules. Hydroponic experiments were conducted to investigate the effects of Mn@LNS-EL on rice growth and the cadmium and manganese contents in the roots and shoots of rice under cadmium stress conditions. The results revealed that the treatment with Mn@LNS-EL markedly alleviated the inhibitory effects of cadmium on rice growth, leading to notably lower cadmium levels in the rice roots and shoots compared to the specimens treated without manganese fertilizer. Specifically, there was a reduction of 37.9 % in the root cadmium content and a 17.1 % decrease in the shoot cadmium content. In conclusion, this study presents an innovative approach for the high-value utilization of lignin through effective encapsulation and slow-release mechanisms of trace-element fertilizers while offering a promising strategy for efficiently remediating cadmium pollution in rice.


Asunto(s)
Oryza , Contaminantes del Suelo , Oligoelementos , Manganeso/farmacología , Lignina/farmacología , Fertilizantes/análisis , Cadmio/farmacología , Agua/farmacología , Contaminantes del Suelo/farmacología , Raíces de Plantas/química , Suelo
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