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1.
Nature ; 613(7942): 60-65, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36288749

RESUMO

Dye-sensitized solar cells (DSCs) convert light into electricity by using photosensitizers adsorbed on the surface of nanocrystalline mesoporous titanium dioxide (TiO2) films along with electrolytes or solid charge-transport materials1-3. They possess many features including transparency, multicolour and low-cost fabrication, and are being deployed in glass facades, skylights and greenhouses4. Recent development of sensitizers5-10, redox mediators11-13 and device structures14 has improved the performance of DSCs, particularly under ambient light conditions14-17. To further enhance their efficiency, it is pivotal to control the assembly of dye molecules on the surface of TiO2 to favour charge generation. Here we report a route of pre-adsorbing a monolayer of a hydroxamic acid derivative on the surface of TiO2 to improve the dye molecular packing and photovoltaic performance of two newly designed co-adsorbed sensitizers that harvest light quantitatively across the entire visible domain. The best performing cosensitized solar cells exhibited a power conversion efficiency of 15.2% (which has been independently confirmed) under a standard air mass of 1.5 global simulated sunlight, and showed long-term operational stability (500 h). Devices with a larger active area of 2.8 cm2 exhibited a power conversion efficiency of 28.4% to 30.2% over a wide range of ambient light intensities, along with high stability. Our findings pave the way for facile access to high-performance DSCs and offer promising prospects for applications as power supplies and battery replacements for low-power electronic devices18-20 that use ambient light as their energy source.

2.
Plant Cell ; 35(8): 2952-2971, 2023 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-37132478

RESUMO

Heat stress (HS) adversely affects plant growth and productivity. The Class A1 HS transcription factors (HSFA1s) act as master regulators in the plant response to HS. However, how HSFA1-mediated transcriptional reprogramming is modulated during HS remains to be elucidated. Here, we report that a module formed by the microRNAs miR165 and miR166 and their target transcript, PHABULOSA (PHB), regulates HSFA1 at the transcriptional and translational levels to control plant HS responses. HS-triggered induction of MIR165/166 in Arabidopsis thaliana led to decreased expression of target genes including PHB. MIR165/166 overexpression lines and mutations in miR165/166 target genes enhanced HS tolerance, whereas miR165/166 knockdown lines and plants expressing a miR165/166-resistant form of PHB were sensitive to HS. PHB directly repressed the transcription of HSFA1s and globally modulated the expression of HS-responsive genes. PHB and HSFA1s share a common target gene, HSFA2, which is essential for activation of plant responses to HS. PHB physically interacted with HSFA1s and exerted an antagonistic effect on HSFA1 transcriptional activity. PHB and HSFA1s co-regulated transcriptome reprogramming upon HS. Together, these findings indicate that heat-triggered regulation of the miR165/166-PHB module controls HSFA1-mediated transcriptional reprogramming and plays a critical role during HS in Arabidopsis.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , MicroRNAs , Termotolerância , Termotolerância/genética , Proteínas de Arabidopsis/metabolismo , Resposta ao Choque Térmico/genética , Arabidopsis/metabolismo , Fatores de Transcrição de Choque Térmico/genética , Fatores de Transcrição de Choque Térmico/metabolismo , Regulação da Expressão Gênica de Plantas/genética , MicroRNAs/genética , MicroRNAs/metabolismo
3.
Pharmacol Res ; 202: 107133, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38458367

RESUMO

Altered glycosylation profiles have been correlated with potential drug targets in various diseases, including Alzheimer's disease (AD). In this area, the linkage between bisecting N-acetylglucosamine (GlcNAc), a product of N-acetylglucosaminyltransferase III (GnT-III), and AD has been recognized, however, our understanding of the cause and the causative role of this aberrant glycosylation in AD are far from completion. Moreover, the effects and mechanisms of glycosylation-targeting interventions on memory and cognition, and novel targeting strategies are worth further study. Here, we showed the characteristic amyloid pathology-induced and age-related changes of GnT-III, and identified transcription factor 7-like 2 as the key transcription factor responsible for the abnormal expression of GnT-III in AD. Upregulation of GnT-III aggravated cognitive dysfunction and Alzheimer-like pathologies. In contrast, loss of GnT-III could improve cognition and alleviate pathologies. Furthermore, we found that an increase in bisecting GlcNAc modified ICAM-1 resulted in impairment of microglial responses, and genetic inactivation of GnT-III protected against AD mechanistically by blocking the aberrant glycosylation of ICAM-1 and subsequently modulating microglial responses, including microglial motility, phagocytosis ability, homeostatic/reactive state and neuroinflammation. Moreover, by target-based screening of GnT-III inhibitors from FDA-approved drug library, we identified two compounds, regorafenib and dihydroergocristine mesylate, showing pharmacological potential leading to modulation of aberrant glycosylation and microglial responses, and rescue of memory and cognition deficits.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/metabolismo , Glicosilação , Molécula 1 de Adesão Intercelular/metabolismo , Microglia/metabolismo , Cognição
4.
Int J Mol Sci ; 25(3)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38338913

RESUMO

DNA methylation and chromatin accessibility play important roles in gene expression, but their function in subgenome expression dominance remains largely unknown. We conducted comprehensive analyses of the transcriptome, DNA methylation, and chromatin accessibility in liver and muscle tissues of allotetraploid common carp, aiming to reveal the function of epigenetic modifications in subgenome expression dominance. A noteworthy overlap in differential expressed genes (DEGs) as well as their functions was observed across the two subgenomes. In the promoter and gene body, the DNA methylation level of the B subgenome was significantly different than that of the A subgenome. Nevertheless, differences in DNA methylation did not align with changes in homoeologous biased expression across liver and muscle tissues. Moreover, the B subgenome exhibited a higher prevalence of open chromatin regions and greater chromatin accessibility, in comparison to the A subgenome. The expression levels of genes located proximally to open chromatin regions were significantly higher than others. Genes with higher chromatin accessibility in the B subgenome exhibited significantly elevated expression levels compared to the A subgenome. Contrastingly, genes without accessibility exhibited similar expression levels in both subgenomes. This study contributes to understanding the regulation of subgenome expression dominance in allotetraploid common carp.


Assuntos
Carpas , Metilação de DNA , Animais , Carpas/genética , Genoma de Planta , Cromatina/genética , Poliploidia , Regulação da Expressão Gênica de Plantas
5.
Molecules ; 29(2)2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38257244

RESUMO

Thirty-eight new 4-amino-3,5-dicholo-6-(1H-indazolyl)-2-picolinic acids and 4-amino-3,5-dicholo-6-(2H-indazolyl)-2-picolinic acids were designed by scaffold hopping and synthesized to discover potential herbicidal molecules. All the new compounds were tested to determine their inhibitory activities against Arabidopsis thaliana and the root growth of five weeds. In general, the synthesized compounds exhibited excellent inhibition properties and showed good inhibitory effects on weed root growth. In particular, compound 5a showed significantly greater root inhibitory activity than picloram in Brassica napus and Abutilon theophrasti Medicus at the concentration of 10 µM. The majority of compounds exhibited a 100% post-emergence herbicidal effect at 250 g/ha against Amaranthus retroflexus and Chenopodium album. We also found that 6-indazolyl-2-picolinic acids could induce the up-regulation of auxin genes ACS7 and NCED3, while auxin influx, efflux and auxin response factor were down-regulated, indicating that 6-indazolyl-2-picolinic acids promoted ethylene release and ABA production to cause plant death in a short period, which is different in mode from other picolinic acids.


Assuntos
Arabidopsis , Herbicidas , Herbicidas/farmacologia , Ácidos Picolínicos/farmacologia , Picloram , Transporte Biológico , Ácidos Indolacéticos/farmacologia
6.
Ann Surg Oncol ; 30(12): 7172-7180, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37543550

RESUMO

BACKGROUND: Surgery is the primary treatment for locally advanced differentiated thyroid cancer (DTC). However, some locally advanced patients are not candidates for R0/1 resection. There is limited evidence of neoadjuvant treatment in locally advanced DTC. Surufatinib targets multiple kinases, which is efficient, tolerable, and safe in patients with radioiodine-refractory DTC. In addition, surufatinib plus toripalimab (an anti-PD-1 antibody) showed encouraging antitumor activity in advanced solid tumors. This study was designed to evaluate the efficacy and safety of surufatinib plus toripalimab in locally advanced DTC in the neoadjuvant setting. METHODS: In this single-arm, phase II study, patients with pathologically confirmed unresectable or borderline resectable DTC were eligible and received a combination of 250 mg of surufatinib (orally daily) with 240 mg of toripalimab (intravenous, every 3 weeks). Treatment continued until satisfied for curative surgery, disease progression, withdrawal of consent, unacceptable toxicity, or investigator decision. Primary endpoint was objective response rate (ORR). Secondary endpoints included R0/1 resection rate, adverse events (AEs), etc. RESULTS: Ten patients were enrolled and received at least 4 cycles of treatment. The ORR was 60%. Nine patients received R0/1 resections after neoadjuvant treatment. The median best percentage change in the sum of the target lesion diameter was 32%. Most adverse events (AEs) were grade 1 or 2. CONCLUSIONS: Surufatinib in combination with toripalimab as neoadjuvant therapy for locally advanced DTC was feasible, and the majority of patients achieved R0/1 resection. It represents a new option for locally advanced DTC and needs further investigation.

7.
Eur Radiol ; 33(12): 9063-9073, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37439940

RESUMO

OBJECTIVES: To establish a computed tomography (CT)-based scale to evaluate the resectability of locally advanced thyroid cancer. METHODS: This twin-centre retrospective study included 95 locally advanced thyroid cancer patients from the 1st centre as the training cohort and 31 patients from the 2nd centre as the testing cohort, who were categorised into the resectable and unresectable groups. Three radiologists scored the CT scans of each patient by evaluating the extension to the recurrent laryngeal nerve (RLN), trachea, oesophagus, artery, vein, soft tissue, and larynx. A 14-score scale (including all comprised structures) and a 12-score scale (excluding larynx) were developed. Receiver-operating characteristic (ROC) analysis was used to evaluate the performance of the scales. Stratified fivefold cross-validation and external verification were used to validate the scale. RESULTS: In the training cohort, compromised RLN (p < 0.001), trachea (p = 0.001), oesophagus (p = 0.002), artery (p < 0.001), vein (p = 0.005), and soft tissue (p < 0.001) were predictors for unresectability, while compromised larynx (p = 0.283) was not. The 12-score scale (AUC = 0.882, 95%CI: 0.812-0.952) was not inferior to the 14-score scale (AUC = 0.891, 95%CI: 0.823-0.960). In subgroup analysis, the AUCs of the 12-score scale were 0.826 for treatment-naïve patients and 0.976 for patients with prior surgery. The 12-score scale was further validated with a fivefold cross-validation analysis, with an overall accuracy of 78.9-89.4%. Finally, external validation using the testing cohort showed an AUC of 0.875. CONCLUSIONS: The researchers built a CT-based 12-score scale to evaluate the resectability of locally advanced thyroid cancer. Validation with a larger sample size is required to confirm the efficacy of the scale. CLINICAL RELEVANCE STATEMENT: This 12-score CT scale would help clinicians evaluate the resectability of locally advanced thyroid cancer. KEY POINTS: • The researchers built a 12-score CT scale (including recurrent laryngeal nerve, trachea, oesophagus, artery, vein, and soft tissue) to evaluate the resectability of locally advanced thyroid cancer. • This scale has the potential to help clinicians make treatment plans for locally advanced thyroid cancer.


Assuntos
Laringe , Neoplasias da Glândula Tireoide , Humanos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgia
8.
Phytother Res ; 37(9): 3867-3897, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37449926

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is a common condition that is prevalent in patients who consume little or no alcohol, and is characterized by excessive fat accumulation in the liver. The disease is becoming increasingly common with the rapid economic development of countries. Long-term accumulation of excess fat can lead to NAFLD, which represents a global health problem with no effective therapeutic approach. NAFLD is a complex, multifaceted pathological process that has been the subject of extensive research over the past few decades. Herbal medicines have gained attention as potential therapeutic agents to prevent and treat NAFLD due to their high efficacy and low risk of side effects. Our overview is based on a PubMed and Web of Science database search as of Dec 22 with the keywords: NAFLD/NASH Natural products and NAFLD/NASH Herbal extract. In this review, we evaluate the use of herbal medicines in the treatment of NAFLD. These natural resources have the potential to inform innovative drug research and the development of treatments for NAFLD in the future.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Extratos Vegetais/uso terapêutico
9.
Int J Mol Sci ; 25(1)2023 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-38203492

RESUMO

Epigenetic modifications are critical in precisely regulating gene expression. The common carp (Cyprinus carpio) is an economically important fish species, and females exhibit faster growth rates than males. However, the studies related to epigenetic modifications in the common carp gonads are limited. In this study, we conducted the Assay for Transposase Accessible Chromatin sequencing (ATAC-seq) and Bisulfite sequencing (BS-seq) to explore the roles of epigenetic modifications in the common carp gonads. We identified 84,207 more accessible regions and 77,922 less accessible regions in ovaries compared to testes, and some sex-biased genes showed differential chromatin accessibility in their promoter regions, such as sox9a and zp3. Motif enrichment analysis showed that transcription factors (TFs) associated with embryonic development and cell proliferation were heavily enriched in ovaries, and the TFs Foxl2 and SF1 were only identified in ovaries. We also analyzed the possible regulations between chromatin accessibility and gene expression. By BS-seq, we identified 2087 promoter differentially methylated genes (promoter-DMGs) and 5264 gene body differentially methylated genes (genebody-DMGs) in CG contexts. These genebody-DMGs were significantly enriched in the Wnt signaling pathway, TGF-beta signaling pathway, and GnRH signaling pathway, indicating that methylation in gene body regions could play an essential role in sex maintenance, just like methylation in promoter regions. Combined with transcriptomes, we revealed that the expression of dmrtb1-like, spag6, and fels was negatively correlated with their methylation levels in promoter regions. Our study on the epigenetic modifications of gonads contributes to elucidating the molecular mechanism of sex differentiation and sex maintenance in the common carp.


Assuntos
Carpas , Cromatina , Feminino , Animais , Masculino , Cromatina/genética , Metilação de DNA , Carpas/genética , Epigênese Genética , Gônadas
10.
Molecules ; 28(15)2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-37570686

RESUMO

Alzheimer's disease (AD) is a prevalent degenerative condition that is increasingly affecting populations globally. American ginseng (AG) has anti-AD bioactivity, and ginsenosides, as the main active components of AG, have shown strong anti-AD effects in both in vitro and in vivo studies. It has been reported that ginsenosides can inhibit amyloid ß-protein (Aß) production and deposition, tau phosphorylation, apoptosis and cytotoxicity, as well as possess anti-oxidant and anti-inflammatory properties, thus suppressing the progression of AD. In this review, we aim to provide a comprehensive overview of the pathogenesis of AD, the potential anti-AD effects of ginsenosides found in AG, and the underlying molecular mechanisms associated with these effects. Additionally, we will discuss the potential use of AG in the treatment of AD, and how ginsenosides in AG may exert more potent anti-AD effects in vivo may be a direction for further research.


Assuntos
Doença de Alzheimer , Ginsenosídeos , Panax , Humanos , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Apoptose
11.
Molecules ; 28(2)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36677619

RESUMO

Thirty novel diamide compounds combining pyrazolyl and polyfluoro-substituted phenyl groups into alanine or 2-aminobutyric acid skeletons were designed and synthesized with pyflubumide as the lead compound to develop potent and environmentally friendly pesticides. The preliminary bioassay results indicated that the new compounds containing the para-hexa/heptafluoroisopropylphenyl moiety exhibit fungicidal, insecticidal, and acaricidal activities. This is the first time that the para-hexa/heptafluoroisopropylphenyl group is a key fragment of the fungicidal activity of new N-phenyl amide compounds. Most of the target compounds exhibited moderate to good insecticidal activity against Aphis craccivora at a concentration of 400 µg/mL, and some showed moderate activity at a concentration of 200 µg/mL; in particular, compounds I-4, II-a-10, and III-26 displayed higher than 78% lethal rates at 200 µg/mL. Compound II-a-14 exhibited a 61.1% inhibition at 200 µg/mL for Tetranychus cinnabarinus. In addition, some of the target compounds exhibited good insecticidal activities against Plutella xylostella at a concentration of 200 µg/mL; the mortalities of compounds I-1, and II-a-15 were 76.7% and 70.0%, respectively. Preliminary analysis of the structure-activity relationship (SAR) indicated that the insecticidal and acaricidal activities varied significantly depending on the type of substituent and substitution pattern. The fungicidal activity results showed that compounds I-1, II-a-10, II-a-17, and III-26 exhibited good antifungal effects. Enzymatic activity experiments and in vivo efficacy of compound II-a-10 were conducted and discussed.


Assuntos
Acaricidas , Fungicidas Industriais , Inseticidas , Mariposas , Animais , Inseticidas/farmacologia , Diamida/farmacologia , Alanina/farmacologia , Desenho de Fármacos , Relação Estrutura-Atividade , Fungicidas Industriais/farmacologia , Estrutura Molecular
12.
Molecules ; 28(3)2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36771096

RESUMO

Picolinic acid and picolinate compounds are a remarkable class of synthetic auxin herbicides. In recent years, two new picolinate compounds, halauxifen-methyl (ArylexTM active) and florpyrauxifen-benzyl (RinskorTM active), have been launched as novel herbicides. Using their structural skeleton as a template, 33 4-amino-3,5-dicholor-6-(5-aryl-substituted-1-pytazolyl)-2-picolinic acid compounds were designed and synthesized for the discovery of compounds with potent herbicidal activity. The compounds were tested for inhibitory activity against the growth of Arabidopsis thaliana roots, and the results demonstrated that the IC50 value of compound V-7 was 45 times lower than that of the halauxifen-methyl commercial herbicide. Molecular docking analyses revealed that compound V-7 docked with the receptor auxin-signaling F-box protein 5 (AFB5) more intensively than picloram. An adaptive three-dimensional quantitative structure-activity relationship model was constructed from these IC50 values to guide the next step of the synthetic strategy. Herbicidal tests of the new compounds indicated that compound V-8 exhibited better post-emergence herbicidal activity than picloram at a dosage of 300 gha-1, and it was also safe for corn, wheat, and sorghum at this dosage. These results demonstrated that 6-(5-aryl-substituted-1-pyrazolyl)-2-picolinic acid compounds could be used as potential lead structures in the discovery of novel synthetic auxin herbicides.


Assuntos
Arabidopsis , Herbicidas , Herbicidas/química , Picloram , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , Arabidopsis/metabolismo , Ácidos Indolacéticos/metabolismo
13.
Molecules ; 28(18)2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37764423

RESUMO

(1) Background: Solanum nigrum L. is a plant of the genus Solanum in the family Solanaceae and is commonly used to treat tumors. Solasonin (SS) is a steroidal alkaloid extracted from Solanum nigrum L. that has anti-colorectal cancer (CRC) activity. (2) Methods: Column chromatography, semi-preparative HPLC and cellular activity screening were used to isolate potential anti-CRC active compounds in Solanum nigrum L., and structure identification using 1H-NMR and 13C-NMR techniques. Expression levels of HDAC in CRC were mined in the UALCAN database. The in vitro effects of SS on SW620 cell line and its mechanism were examined via Western blot, EdU staining, flow cytometry and immunofluorescence. CRC xenograft model and IHC staining were mainly used to evaluate the role of SS in vivo. (3) Results: The results showed that SS was the most potent anti-CRC component in Solanum nigrum L., which induced apoptosis and cell cycle arrest in the SW620 cell line. HDAC was highly expressed in CRC. The treatment of SW620 cell line with SS resulted in a significant downregulation of HDAC, an increase in the level of P53 acetylation and a subsequent increase in the level of P21. The in vivo validation results showed that SS could effectively inhibit CRC growth, which was associated with the downregulation of HDAC. (4) Conclusions: SS treatment for CRC mainly works through the induction of apoptosis and cycle arrest, and its mechanism of action is mainly related to HDAC-induced P53 acetylation, and the HDAC/P53 signaling pathway may be a potential pathway for the treatment of CRC.


Assuntos
Neoplasias , Solanum nigrum , Solanum , Humanos , Acetilação , Proteína Supressora de Tumor p53/genética , Regulação para Baixo
14.
J Biochem Mol Toxicol ; 36(4): e22994, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35179253

RESUMO

Atherosclerosis (AS) is a chronic inflammatory disease with the formation and accumulation of macrophage-derived foam cells in the subendothelial space of blood vessels as one major characteristic. Insulin-like growth factor 2 messenger RNA (mRNA) binding protein 1 (IGF2BP1) is an RNA-binding factor and its elevation has been reported to be associated with macrophage infiltration into the atherosclerotic vascular wall. This study aims to investigate the roles of IGF2BP1 in AS-associated foam cell formation. Herein, ApoE-/- mice fed with high-fat diet developed atherosclerotic lesions in the aorta, where IGF2BP1 expression was upregulated and autophagy was impaired. IGF2BP1 expressed in F4/80+ macrophages and coexisted with p62. In vitro, IGF2BP1 expression was upregulated in RAW264.7 macrophages exposed to oxidized low-density lipoprotein (ox-LDL) (100 µg/ml). Interestingly, silencing of IGF2BP1 ameliorated ox-LDL-induced lipid accumulation and inflammation, and enhanced autophagic flux in macrophages. Furthermore, the expression of RUNX family transcription factor 1 (RUNX1), a gene that is able to inhibit autophagy in multiple cell types, was elevated in atherosclerotic aortas and in ox-LDL-treated macrophages. In addition, RNA immunoprecipitation results revealed that IGF2BP1 is bound to RUNX1 mRNA. Alterations induced by IGF2BP1 knockdown in ox-LDL-treated macrophages were abolished by RUNX1 overexpression. Furthermore, after autophagy inhibitor 3-methyladenine administration, silencing of IGF2BP1-reduced lipid accumulation and inflammation were recovered in RAW264.7 cells. In summary, our study demonstrated that silencing of IGF2BP1 restrained ox-LDL-induced lipid accumulation and inflammation by reducing RUNX1 expression and facilitating autophagy in macrophages. IGF2BP1/RUNX1 axis may be considered as a potential therapeutic target in AS.


Assuntos
Aterosclerose , Subunidade alfa 2 de Fator de Ligação ao Core , Animais , Aterosclerose/metabolismo , Autofagia , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Inflamação/metabolismo , Lipoproteínas LDL/metabolismo , Macrófagos/metabolismo , Camundongos , RNA/metabolismo , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA
15.
Molecules ; 27(21)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36364084

RESUMO

Fourteen compounds were isolated from Pueraria lobata (Willd.) Ohwi by column chromatography and preparative thin-layer chromatography; the structures were identified by spectroscopic analysis and compared with data reported in the literature. Seven compounds were isolated and identified from Pueraria lobata for the first time: Linoleic acid, Sandwicensin, Isovanillin, Ethyl ferulate, Haginin A, Isopterofuran, 3'.7-Dihydroxyisoflavan. The other 10 compounds were structurally identified as follows: Lupenone, Lupeol, ß-sitosterol, Genistein, Medicarpin, Coniferyl Aldehyde, Syringaldehyde. All compounds were evaluated for their ability to inhibit SW480 and SW620 cells using the CCK-8 method; compound 5 (Sandwicensin) had the best activity, and compounds 6, 9, 11 and 12 exhibited moderate inhibitory activity. In addition, the targets and signaling pathways of Sandwicensin treatment for CRC were mined using network pharmacology, and MAPK3, MTOR, CCND1 and CDK4 were found to be closely associated with Sandwicensin treatment for CRC; the GO and KEGG analysis showed that Sandwicensin may directly regulate the cycle, proliferation and apoptosis of CRC cells through cancer-related pathways.


Assuntos
Isoflavonas , Neoplasias , Pueraria , Humanos , Pueraria/química , Raízes de Plantas/química , Genisteína , Isoflavonas/química
16.
J Virol ; 94(9)2020 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-32075935

RESUMO

Human enteroviruses (EVs), including coxsackieviruses, the numbered enteroviruses, and echoviruses, cause a wide range of diseases, such as hand, foot, and mouth disease (HFMD), encephalitis, myocarditis, acute flaccid myelitis (AFM), pneumonia, and bronchiolitis. Therefore, broad-spectrum anti-EV drugs are urgently needed to treat EV infection. Here, we demonstrate that FNC (2'-deoxy-2'-ß-fluoro-4'-azidocytidine), a small nucleoside analog inhibitor that has been demonstrated to be a potent inhibitor of HIV and entered into a clinical phase II trial in China, potently inhibits the viral replication of a multitude of EVs, including enterovirus 71 (EV71), coxsackievirus A16 (CA16), CA6, EVD68, and coxsackievirus B3 (CVB3), at the nanomolar level. The antiviral mechanism of FNC involves mainly positive- and negative-strand RNA synthesis inhibition by targeting and competitively inhibiting the activity of EV71 viral RNA-dependent RNA polymerase (3Dpol), as demonstrated through quantitative real-time reverse transcription-PCR (RT-qPCR), in vitro 3Dpol activity, and isothermal titration calorimetry (ITC) experiments. We further demonstrated that FNC treatment every 2 days with 1 mg/kg of body weight in EV71 and CA16 infection neonatal mouse models successfully protected mice from lethal challenge with EV71 and CA16 viruses and reduced the viral load in various tissues. These findings provide important information for the clinical development of FNC as a broad-spectrum inhibitor of human EV pathogens.IMPORTANCE Human enterovirus (EV) pathogens cause various contagious diseases such as hand, foot, and mouth disease, encephalitis, myocarditis, acute flaccid myelitis, pneumonia, and bronchiolitis, which have become serious health threats. However, except for the EV71 vaccine on the market, there are no effective strategies to prevent and treat other EV pathogen infections. Therefore, broad-spectrum anti-EV drugs are urgently needed. In this study, we demonstrated that FNC, a small nucleoside analog inhibitor that has been demonstrated to be a potent inhibitor of HIV and entered into a clinical phase II trial in China, potently inhibits the viral replication of a multitude of EVs at the nanomolar level. Further investigation revealed that FNC inhibits positive- and negative-strand RNA synthesis of EVs by interacting and interfering with the activity of EV71 viral RNA-dependent RNA polymerase (3Dpol). Our findings demonstrate for the first time that FNC is an effective broad-spectrum inhibitor for human EV pathogens.


Assuntos
Azidas/farmacologia , Desoxicitidina/análogos & derivados , Enterovirus/genética , Replicação Viral/efeitos dos fármacos , Animais , Azidas/metabolismo , China , Infecções por Coxsackievirus/genética , Desoxicitidina/metabolismo , Desoxicitidina/farmacologia , Enterovirus/metabolismo , Enterovirus Humano A/genética , Enterovirus Humano B/genética , Enterovirus Humano B/metabolismo , Infecções por Enterovirus/virologia , Camundongos , Pirimidinas/metabolismo , Pirimidinas/farmacologia , Carga Viral/efeitos dos fármacos
17.
J Am Chem Soc ; 140(34): 10677-10681, 2018 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-30099869

RESUMO

We report a chiral phosphoric acid catalyzed bromocyclization/regiodivergent reaction of racemic intermediates sequence, which is enabled by anchimeric oxygen borrowing. Different types of alkenes are applicable, and both enantiomers of the bromohydrin products were obtained in generally excellent yields and enantioselectivities. In addition, an example of enantioconvergent synthesis from the two isomeric products is presented.

18.
J Am Chem Soc ; 140(7): 2405-2408, 2018 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-29323883

RESUMO

We report a blue dye, coded as R6, which features a polycyclic aromatic hydrocarbon, 9,19-dihydrobenzo[1',10']phenanthro[3',4':4,5]thieno[3,2-b]benzo[1,10]phenanthro[3,4-d]thiophene, coupled with a diarylamine electron donor and 4-(7-ethynylbenzo[c][1,2,5]thiadiazol-4-yl)benzoic acid acceptor. Dye R6 displays a brilliant sapphire color in a sensitized TiO2 mesoporous film with a Co(II/III) tris(bipyridyl)-based redox electrolyte. The R6 based dye-sensitized solar cell achieves an impressive power conversion efficiency of 12.6% under standard air mass 1.5 global, 100 mW cm-2, and shows a remarkable photostability.

19.
Angew Chem Int Ed Engl ; 57(43): 14125-14128, 2018 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-30126024

RESUMO

The synthesis, characterization, and photovoltaic performance of a series of indacenodithiophene (IDT)-based D-π-A organic dyes with varying electron-accepting units is presented. By control of the electron affinity, perfectly matching energy levels were achieved with a copper(I/II)-based redox electrolyte, reaching a high open-circuit voltage (>1.1 V) while harvesting a large fraction of solar photons at the same time. Besides achieving high power conversion efficiencies (PCEs) for dye-sensitized solar cells (DSCs), that is, 11.2 % under standard AM 1.5 G sunlight, and 28.4 % under a 1000 lux fluorescent light tube, this work provides a possible method for the design and fabrication of low-cost highly efficient DSCs.

20.
Muscle Nerve ; 55(3): 338-343, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27421831

RESUMO

INTRODUCTION: Chronic inflammatory demyelinating polyneuropathy (CIDP) typically presents with a combination of sensory and motor impairments. Tremor is recognized as a common and debilitating feature in CIDP, although the underlying mechanisms are unclear. METHODS: Clinical tremor severity and disability scores were collected prospectively in 25 CIDP patients and compared with 22 neuromuscular controls. RESULTS: Postural and kinetic tremor were significantly more frequent in CIDP patients (80%) than in neuromuscular controls (35%; P < 0.005). Tremor severity and tremor-related disability were also significantly greater in CIDP patients than in controls. Accelerometry data confirmed the presence of a 5.5 Hz postural tremor and a 5 Hz kinetic tremor. CONCLUSIONS: Tremor appears to be a common clinical feature of CIDP that results in significant disability. Sensory and motor impairment may be associated with development of tremor in CIDP. Muscle Nerve 55: 338-343, 2017.


Assuntos
Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/complicações , Equilíbrio Postural/fisiologia , Transtornos de Sensação/etiologia , Tremor/etiologia , Acelerometria , Adulto , Idoso , Idoso de 80 Anos ou mais , Pessoas com Deficiência , Eletromiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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