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1.
Biomater Sci ; 9(21): 7124-7133, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34581318

RESUMO

Rapid hemostasis and antibacterial properties are essential for novel wound dressings to promote wound healing. In particular, timely and rapid hemostasis could be of benefit to reduce the mortality caused by excessive bleeding loss. Herein, we present a novel strategy of combining electrospinning technology with post-modification technology to prepare a multifunctional wound dressing, cellulose diacetate-based composite wound dressing (CDCE), with rapid hemostasis and antibacterial activity. It is interesting that the CDCE wound dressing had superhydrophilicity, high water absorption, and strong absorbing capacity, which could eliminate the exudate around the wound in a timely manner and further promote rapid hemostasis. Additionally, its excellent antibacterial properties could inhibit severe infection in the wound and accelerate wound healing. Based on these advantages, the novel CDCE wound dressing could promote wound contraction and further accelerate wound healing compared with the common traditional wound dressing gauze. Taken together, the multifunctional CDCE wound dressing has high potential for clinical application in the future.


Assuntos
Anti-Infecciosos , Bandagens , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Hemostasia , Cicatrização
2.
Front Pharmacol ; 12: 721273, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34393799

RESUMO

Chronic obstructive pulmonary disease (COPD), a major cause of morbidity and mortality worldwide, is widely considered to be related to cigarette smoke (CS), and viral infections trigger acute exacerbation of COPD (AECOPD). Isoforskolin (ISOF) is a bioactive component from the plant Coleus forskohlii, native to Yunnan in China. It has been demonstrated that ISOF has anti-inflammatory effect on acute lung injury animal models. In the present study, we investigated the efficacy and mechanism of ISOF for the prevention and treatment of AECOPD. Mice were exposed to CS for 18 weeks and then infected with influenza virus A/Puerto Rico/8/34 (H1N1). ISOF (0.5, 2 mg/kg) was intragastrically administered once a day after 8 weeks of exposure to cigarette smoke when the body weight and lung function of model mice declined significantly. The viral load, pulmonary function, lung morphology, Th17 cells, and inflammatory cytokines in lung tissues were evaluated. The expression of nuclear factor κB (NF-κB) and NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome pathways were detected. The results showed that ISOF treatment reduced the viral load in the lung homogenate, decreased the lung index of model mice, and lung pathological injuries were alleviated. ISOF also improved the pulmonary function with increased FEV0.1/FVC and decreased Rn and Rrs. The levels of inflammatory mediators (TNF-α, IL-1ß, IL-6, IL-17A, MCP-1, MIG, IP-10, and CRP) in the lung homogenate were reduced after ISOF treatment. ISOF decreased the proportion of Th17 cells in the lung tissues by the flow cytometry test, and the protein expression levels of RORγt and p-STAT3 were also decreased. Furthermore, ISOF significantly inhibited the activation of NF-κB signaling and NLRP3 inflammasome in the lung tissues of model mice. In conclusion, ISOF alleviates AECOPD by improving pulmonary function and attenuating inflammation via the downregulation of proinflammatory cytokines, Th17/IL-17 A, and NF-κB/NLRP3 pathways.

3.
Phytomedicine ; 91: 153701, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34438230

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by limited airflow due to pulmonary and alveolar abnormalities from exposure to cigarette smoke (CS). Current therapeutic drugs are limited and the development of novel treatments to prevent disease progression is challenging. Isoforskolin (ISOF) from the plant Coleus forskohlii is an effective activator of adenylyl cyclase (AC) isoforms. Previously we found ISOF could attenuate acute lung injury in animal models, while the effect of ISOF on COPD has not been elucidated. PURPOSE: In this study, we aimed to evaluate the efficacy of ISOF on COPD and reveal its potential mechanisms. METHODS: A rat model of COPD was established by long-term exposure to CS, then the rats were orally administered with ISOF (0.5, 1 and 2 mg/kg). The pulmonary function, lung morphology, inflammatory cells and cytokines in serum or bronchoalveolar lavage fluid (BALF) were evaluated. Transcriptomics, proteomics and network pharmacology analysis were utilized to identify potential mechanisms of ISOF. Droplet digital PCR was used to detect the mRNA expression of AC1-10 in donor lung tissues. AC activation was determined in recombinant human embryonic kidney 293 (HEK293) cells stably expressing human AC isoforms. In addition, ISOF caused trachea relaxation ex vivo were assessed in isolated trachea rings from guinea pigs. RESULTS: ISOF significantly ameliorated pathological damage of lung tissue and improved pulmonary function in COPD rats. ISOF treatment decreased the number of inflammatory cells in peripheral blood, and also the levels of pro-inflammatory cytokines in serum and BALF. Consistent with omics-based analyses, ISOF markedly downregulated the mTOR level in lung tissue. Flow cytometry analysis revealed that ISOF treatment reduced the ratio of Th17/Treg cells in peripheral blood. Furthermore, the expression levels of AC1 and AC2 are relatively higher than other AC isoforms in normal lung tissues, and ISOF could potently activate AC1 and AC2 in vitro and significantly relax isolated guinea pig trachea. CONCLUSION: Collectively, our studies suggest that ISOF exerts its anti-COPD effect by improving lung function, anti-inflammation and trachea relaxation, which may be related to AC activation, mTOR signaling and Th17/Treg balance.


Assuntos
Adenilil Ciclases , Colforsina/farmacologia , Doença Pulmonar Obstrutiva Crônica , Fumaça , Animais , Coleus/química , Cobaias , Células HEK293 , Humanos , Compostos Fitoquímicos/farmacologia , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Ratos , Fumaça/efeitos adversos , Fumar
4.
Ying Yong Sheng Tai Xue Bao ; 32(4): 1498-1508, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33899419

RESUMO

Water and nitrogen are two important factors controlling rice growth and development. Suitable water-nitrogen interaction can alter nitrogen forms and oxygen environmental factors via regulating water content in the rhizosphere of paddy soil, promote the construction of root morphology, improve leaf photosynthesis and the allocation equilibrium of the photosynthetic products between the source and sink organs, and consequently increase rice population quality and grain yield. The microbial regulation mechanisms driven by the environmental factors (e.g. water, nitrogen and oxygen) also play an important role in improving nitrogen utilization efficiency in rice-soil system. Here, we reviewed the research progress in water-nitrogen interaction, and briefly discussed the effects of water, nitrogen form, and dissolved oxygen on rice growth, photosynthesis, carbon and nitrogen metabolism, nitrogen conversion and the underlying microbiological mechanism. We proposed several key directions for future researches: 1) to quantitatively investigate the spatial and temporal variations of dissolved oxygen in rhizosphere and their dominant environmental drivers under different water and nitrogen regimes; 2) to evaluate the responses of root-sourced signal to rhizosphere dissolved oxygen in different rice genotypes, and uncover its intrinsic mechanisms involved in rice growth and development; 3) to investigate the effects of key microbial process driven by the rhizosphere oxygen environment on the soil nitrogen conversion and rice nitrogen utilization.


Assuntos
Oryza , Solo , Nitrogênio , Oxigênio , Fotossíntese , Água
5.
Clin Exp Pharmacol Physiol ; 47(10): 1731-1739, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32424975

RESUMO

Vascular dementia (VaD), caused by stroke or small vessel disease, is the second-most common type of dementia after Alzheimer's disease (AD). Donepezil is an acetylcholinesterase inhibitor that is currently used in patients with mild to moderate AD, and has recently been shown to improve cognitive performance in patients with VaD. In this study, we evaluated the effects of donepezil on VaD, and investigated the underlying molecular mechanisms of action. VaD was established by ligation of the bilateral common carotid artery occlusion (BCCAO). Executive function was tested by the Morris water maze (MWM) test and the attentional set shifting task (ASST). Our results showed that donepezil improved executive dysfunction and cognitive flexibility in BCCAO rats. In addition, we showed that donepezil treatment decreased the level of Aß1-42 in BCCAO rats by enzyme-linked immunosorbent assay. Post-translational modifications (PTMs) are known to be critical mechanisms in the regulation of various cellular processes. Furthermore, PTMs have been linked to the central nervous system, which highlights the importance of PTMs in neurodegenerative diseases. In this study, we used western blot analysis to identify several novel PTMs in the hippocampus of BCCAO rats that were treated with or without donepezil. The data revealed that lysine propionylation, 2-hydroxyisobutyrylation, butyrylation, succinylation, and crotonylation were elevated in the hippocampus of BCCAO rats when compared to sham rats. This increase was abolished by donepezil treatment. Taken together, we speculate that donepezil treatment improves cognitive function in our animal model of VaD, possibly by reducing aberrant acyl-PTMs.

6.
Thromb Haemost ; 120(4): 607-619, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32289860

RESUMO

A native fucosylated glycosaminoglycan from sea cucumber Holothuria fuscopunctata (nHG), mainly branched with Fuc3S4S, exhibited potent anticoagulant activity by intrinsic tenase iXase (FIXa-FVIIIa complex) and antithrombin-dependent factor IIa (FIIa) inhibition, but also had the effects of FXII activation and platelet aggregation. For screening a selective iXase inhibitor, depolymerized nHG (dHG-1 ∼ -6) and a pure octasaccharide (oHG-8) were prepared. Like nHG, dHG-1 ∼ -6 and oHG-8 could potently inhibit iXase, and competitive binding assay indicated that dHG-5 and oHG-8 could bind to FIXa. Nevertheless, dHG-5 and oHG-8 had no effects on FXII and platelet activation. nHG, dHG-5, and oHG-8 could significantly prolong the activated partial thromboplastin time of human, rat, and rabbit plasma. In the rat deep venous thrombosis model, dHG-5 and oHG-8 showed potent antithrombotic effects in a dose-dependent manner, while the thrombus inhibition rate of nHG at high dose was markedly reduced. Additionally, dHG-5 and oHG-8 did not increase bleeding at the doses up to 10-fold of the effectively antithrombotic doses compared with nHG and low molecular weight heparin in the mice tail-cut model. Considering that dHG-5 possesses strong anti-iXase and antithrombotic activities, and its preparation process is simpler and its yield is higher compared with oHG-8, it might be a promising antithrombotic candidate.


Assuntos
Anticoagulantes/metabolismo , Anticoagulantes/uso terapêutico , Cisteína Endopeptidases/metabolismo , Glicosaminoglicanos/metabolismo , Hemorragia/tratamento farmacológico , Proteínas de Neoplasias/metabolismo , Trombose Venosa/tratamento farmacológico , Animais , Anticoagulantes/química , Coagulação Sanguínea , Cisteína Endopeptidases/química , Cisteína Endopeptidases/uso terapêutico , Modelos Animais de Doenças , Glicosaminoglicanos/química , Glicosaminoglicanos/uso terapêutico , Humanos , Masculino , Camundongos , Camundongos Endogâmicos , Proteínas de Neoplasias/química , Proteínas de Neoplasias/uso terapêutico , Polimerização , Coelhos , Ratos , Ratos Sprague-Dawley , Pepinos-do-Mar
7.
Lancet Gastroenterol Hepatol ; 5(3): 267-275, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31926918

RESUMO

BACKGROUND: Chemoprevention of colorectal adenoma and colorectal cancer remains an important public health goal. The present study aimed to investigate the clinical potential and safety of berberine for prevention of colorectal adenoma recurrence. METHODS: This double-blind, randomised, placebo-controlled trial was done in seven hospital centres across six provinces in China. Individuals aged 18-75 years who had at least one but no more than six histologically confirmed colorectal adenomas that had undergone complete polypectomy within the 6 months before recruitment were recruited and randomly assigned (1:1) to receive berberine (0·3 g twice daily) or placebo tablets via block randomisation (block size of six). Participants were to undergo a first follow-up colonoscopy 1 year after enrolment, and if no colorectal adenomas were detected, a second follow-up colonoscopy at 2 years was planned. The study continued until the last enrolled participant reached the 2-year follow-up point. All participants, investigators, endoscopists, and pathologists were blinded to treatment assignment. The primary efficacy endpoint was the recurrence of adenomas at any follow-up colonoscopy. Analysis was based on modified intention-to-treat, with the full analysis set including all randomised participants who received at least one dose of study medication and who had available efficacy data. The study is registered with ClinicalTrials.gov, number NCT02226185; the trial has ended and this report represents the final analysis. FINDINGS: Between Nov 14, 2014, and Dec 30, 2016, 553 participants were randomly assigned to the berberine group and 555 to the placebo group. The full analysis set consisted of 429 participants in the berberine group and 462 in the placebo group. 155 (36%) participants in the berberine group and 216 (47%) in the placebo group were found to have recurrent adenoma during follow-up (unadjusted relative risk ratio for recurrence 0·77, 95% CI 0·66-0·91; p=0·001). No colorectal cancers were detected during follow-up. The most common adverse event was constipation (six [1%] of 446 patients in the berberine group vs one [<0·5%] of 478 in the placebo group). No serious adverse events were reported. INTERPRETATION: Berberine 0·3 g twice daily was safe and effective in reducing the risk of recurrence of colorectal adenoma and could be an option for chemoprevention after polypectomy. FUNDING: National Natural Science Foundation of China.


Assuntos
Adenoma/prevenção & controle , Antineoplásicos Fitogênicos/uso terapêutico , Berberina/uso terapêutico , Neoplasias Colorretais/patologia , Adenoma/patologia , Adenoma/cirurgia , Adolescente , Adulto , Assistência ao Convalescente , Idoso , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/efeitos adversos , Berberina/administração & dosagem , Berberina/efeitos adversos , Quimioprevenção/métodos , China/epidemiologia , Colonoscopia/métodos , Colonoscopia/estatística & dados numéricos , Neoplasias Colorretais/epidemiologia , Método Duplo-Cego , Humanos , Análise de Intenção de Tratamento/métodos , Pessoa de Meia-Idade , Placebos/administração & dosagem , Plantas Medicinais/efeitos adversos , Recidiva , Segurança , Adulto Jovem
8.
Pharmacology ; 105(7-8): 386-396, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31752010

RESUMO

Vascular dementia (VaD) is the second most common type of dementia and has become a major public health challenge as the global population ages. VaD is caused by cerebrovascular disease, and most patients with VaD have been reported to also have Alzheimer's pathologies, which is the formation of neurofibrillary tangles and amyloid plaques that are mainly composed of hyperphosphorylated Tau and amyloid ß (Aß) respectively. However, the mechanisms of VaD are not completely understood, and very few drugs are available to treat this condition. Gastrodin (Gas) is the main bioactive component of the traditional Chinese herbal plant named Tian Ma (Gastrodia elata), and it has been used to treat neurasthenia in the clinical practice of Chinese Medicine for many years. Here, we hypothesize that Gas alleviates VaD in a rat model of permanent bilateral common carotid artery occlusion (2-VO)-induced VaD. Based on the results of the Morris water maze test and attention set shift test, either 22.5 or 90 mg/kg/day Gas improved the executive dysfunction and memory impairment of 2-VO rats following an intragastric administration for 4 weeks. Both 22.5 and 90 mg/kg/day Gas reduced Aß1-40 and Aß1-42 plaques in plasma and hippocampus of 2-VO rats. Mechanistically, in 2-VO rats, treatment with Gas (90 mg/kg/day) suppressed Aß plaque deposition by decreasing the hippocampus levels of phosphorylated Tau. Thus, Gas ameliorated the cognitive deficits of 2-VO rats by inhibiting the abnormal phosphorylation of Aß and Tau.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Álcoois Benzílicos/farmacologia , Demência Vascular/tratamento farmacológico , Glucosídeos/farmacologia , Fármacos Neuroprotetores/farmacologia , Proteínas tau/metabolismo , Animais , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/etiologia , Estenose das Carótidas/complicações , Demência Vascular/etiologia , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/patologia , Ratos , Ratos Sprague-Dawley
9.
Gene ; 728: 144279, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31821871

RESUMO

AIM OF THE STUDY: Chronic glomerulonephritis (CGN) is the most common form of primary glomerular disease. Qi Teng Xiao Zhuo granules have been proposed as a prescription of traditional Chinese medicine (TCM) for treatment of CGN, however,the comprehensive molecular mechanism underlying this therapeutic effectremains unclear to date. Our study aimed to evaluate and analyze the possible roles and molecular mechanisms of Qi Teng Xiao Zhuo granule-mediated treatment of CGN induced by adriamycin in rats. MATERIALS AND METHODS: RNA-sequencing and real-time polymerase chain reaction (RT-PCR) were applied to identify specifically expressed long noncoding RNAs (lncRNAs) in glomerular tissues of rats from the control group, adriamycin-induced group, and Qi Teng Xiao Zhuo granules group (n = 3). Differentially expressed lncRNAs and mRNAs (messengerRNAs) were screened out among the 3 groups. Gene ontology (GO) and pathway enrichment analyses were performed to analyze the biological functions and pathways for mRNAs. LncRNA-mRNA co-expression network was constructed to analyse for the genes. The protein-protein interaction (PPI) network was visualized. RESULTS: A total of 473 significantly up and down-regulated lncRNAs, 753 up and down-regulated mRNAs were identified. Additionally, it is worth noting that TOP2a (topoisomerase (DNA) II alpha), with the highest connectivity degree in PPI network, was enriched in variouskinds of pathways. Coding-non-coding gene co-expression networks (CNC network) were drawn based on the correlation analysis between lncRNAs and mRNAs. Ten lncRNAs, NONRATT009275.2, NONRATT025409.2, NONRATT025419.2, MSTRG.7681.1, ENSRNOT00000084373, NONRATT000512.2, NONRATT006734.2, ENSRNOT00000084386, NONRATT021738.2, ENSRNOT00000084080, were selected to analyse the relationship between LncRNAs and Qi Teng Xiao Zhuo granules via the CNC network (Coding-non-coding gene co-expression networks) and GO analysis. Real-time PCR results confirmed that the six lncRNAs were specifically expressed in the Qi Teng Xiao Zhuo granules rats. CONCLUSIONS: The ten lncRNAs might play important roles in the Qi Teng Xiao Zhuo granules treatment of CGN. Key genes, such as Ptprc (protein tyrosine phosphatase, receptor type, C), TOP2a, Fos (FBJ osteosarcoma oncogene), Myc (myelocytomatosis oncogene), etc, may be crucial biomarkers for Qi Teng Xiao Zhuo granules.


Assuntos
Biomarcadores/análise , Medicamentos de Ervas Chinesas/farmacologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Glomerulonefrite/genética , RNA Longo não Codificante/genética , Animais , Doença Crônica , Glomerulonefrite/tratamento farmacológico , Masculino , Mapas de Interação de Proteínas , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley
10.
Sci Rep ; 9(1): 19108, 2019 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-31836776

RESUMO

Tenuifolin was used as a reliable chemical marker for the quality control of Radix Polygalae. The determination of tenuifolin is challenging because the analyte molecule lacks a suitable chromophore. The aim of this study was to establish a microemulsion high-performance liquid chromatography (MELC) method which is robust and sensitive, and can separate and determine tenuifolin in Radix Polygalae using an oil-in-water (O/W) microemulsion mobile phase. The separations were performed on a C18 (4.6 × 250 mm, 5 µm) column at 25 °C using a flow rate of 1.0 mL/min, and an ultraviolet detection wavelength of 210 nm. The microemulsion mobile phase comprised 2.8% (w/v) sodium dodecyl sulfate (SDS), 7.0% (v/v) n-butanol, 0.8% (v/v) n-octane and 0.1% (v/v) aqueous orthophosphate buffer (H3PO4). The linearity analysis of tenuifolin showed a correlation coefficient of 0.9923 in the concentration range of 48.00-960.00 µg/mL. The accuracy of the method based on three concentration levels ranged from 96.23% to 99.28%; the limit of detection (LOD) was 2.34 µg/mL, and the limit of quantification (LOQ) was 6.76 µg/mL. The results of our study indicated that the optimized MELC method was sensitive and robust, and can be widely applied for the separation and determination of tenuifolin in Radix Polygalae.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Diterpenos do Tipo Caurano/análise , Medicamentos de Ervas Chinesas/análise , Emulsões , Saponinas/análise , 1-Butanol , Tampões (Química) , Química Verde , Limite de Detecção , Modelos Lineares , Octanos , Tamanho da Partícula , Fosfatos , Raízes de Plantas/química , Polygala/química , Controle de Qualidade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Dodecilsulfato de Sódio , Espectrofotometria Ultravioleta , Tensoativos , Temperatura
11.
Nat Commun ; 10(1): 3981, 2019 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-31484922

RESUMO

The diverse expression pattern of CD36 reflects its multiple cellular functions. However, the roles of CD36 in colorectal cancer (CRC) remain unknown. Here, we discover that CD36 expression is progressively decreased from adenomas to carcinomas. CD36 loss predicts poor survival of CRC patients. In CRC cells, CD36 acts as a tumor suppressor and inhibits aerobic glycolysis in vitro and in vivo. Mechanically, CD36-Glypcian 4 (GPC4) interaction could promote the proteasome-dependent ubiquitination of GPC4, followed by inhibition of ß-catenin/c-myc signaling and suppression of downstream glycolytic target genes GLUT1, HK2, PKM2 and LDHA. Moreover, disruption of CD36 in inflammation-induced CRC model as well as ApcMin/+ mice model significantly increased colorectal tumorigenesis. Our results reveal a CD36-GPC4-ß-catenin-c-myc signaling axis that regulates glycolysis in CRC development and may provide an intervention strategy for CRC prevention.


Assuntos
Antígenos CD36/genética , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Glicólise/genética , Glipicanas/genética , Proteínas Proto-Oncogênicas c-myc/genética , beta Catenina/genética , Idoso , Animais , Antígenos CD36/metabolismo , Células CACO-2 , Carcinogênese/genética , Linhagem Celular Tumoral , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/terapia , Feminino , Perfilação da Expressão Gênica/métodos , Glipicanas/metabolismo , Células HCT116 , Células HT29 , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-myc/metabolismo , Terapêutica com RNAi/métodos , Transdução de Sinais/genética , Ubiquitinação , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , beta Catenina/metabolismo
12.
J Plant Physiol ; 240: 153003, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31279219

RESUMO

Phosphorus (P) deficiency limits rice production. Increasing the remobilization of P stored in the root cell wall is an efficient way to alleviate P starvation in rice. In the current study, we found that the addition of 50 µM H2O2 significantly increased soluble P content in rice. H2O2 stimulated pectin biosynthesis and increased pectin methylesterase (PME) activity, thus stimulating the release of P from the cell wall in roots. H2O2 also regulates internal P homeostasis by increasing the expression of P transporter genes OsPT2, OsPT6, and OsPT8 at different treatment times. In addition, the H2O2 treatment increased the expression of nitrate reductase (NR) genes OsNIA1 and OsNIA2 and the activity of NR, then increased the accumulation of nitric oxide (NO) in the rice root. The application of the NO donor sodium nitroprusside (SNP) and the H2O2 scavenger 4-hydroxy-TEMPO significantly increased soluble P content by increasing pectin levels and PME activity to enhance the remobilization of P from the cell wall. However, the addition of NO scavenger 2-(4-carboxyphenyl)-4, 4, 5, 5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO) with and without H2O2 had the opposite effect, suggesting that NO functions downstream of H2O2 to increase the remobilization of cell wall P in rice.


Assuntos
Parede Celular/metabolismo , Peróxido de Hidrogênio/metabolismo , Oryza/metabolismo , Fósforo/metabolismo , Raízes de Plantas/metabolismo
13.
Plant Physiol Biochem ; 138: 80-90, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30852240

RESUMO

When boron (B) deficiency and aluminum (Al) toxicity co-exist in acidic soils, crop productivity is limited. In the current study, we found that 3 µM of B pretreatment significantly enhances rice root elongation under Al toxicity conditions. Pretreatment with B significantly decreases the deposition of Al in rice apoplasts, suppresses the synthesis of cell wall pectin, inhibits cell wall pectin methylesterase (PME) activity and its gene expression, and increases the expression of OsSTAR1 and OsSTAR2, which are responsible for reducing the Al content in the cell walls. In addition, B pretreatment significantly increases OsALS1 expression, thereby facilitating the transfer of Al from the cytoplasm to the vacuoles. However, B pretreatment had no effect on Al uptake and citric acid secretion. Pretreatment with B significantly increases the activity of ascorbate peroxidase (APX), peroxidase (POD), and catalase (CAT), thus increasing the elimination rate of H2O2 in rice roots. Co-treatment using B and H2O2 does not increase root growth under Al toxicity conditions; it also improves pectin synthesis, enhances PME activity, and increases Al deposition in root cell walls. However, the co-treatment of B and H2O2 scavenger 4-hydroxy-TEMPO has an opposite effect. The above results indicate that applying B fertilizers in acidic soil can help decrease the side effects of Al toxicity on rice growth.


Assuntos
Alumínio/farmacologia , Boro/farmacologia , Parede Celular/metabolismo , Peróxido de Hidrogênio/metabolismo , Oryza/metabolismo , Raízes de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Proteínas de Plantas/biossíntese
14.
Physiol Plant ; 167(4): 471-487, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30851007

RESUMO

Aluminum (Al3+ ) toxicity in acidic soils limits crop productivity worldwide. In this study, we found that putrescine (PUT) significantly alleviates Al toxicity in rice roots. The addition of 0.1 mM PUT promoted root elongation and reduced the Al content in the root apices of Nipponbare (Nip) and Kasalath (Kas) rice under Al toxicity conditions. Exogenous treatment with PUT reduced the cell wall Al content by reducing polysaccharide (pectin and hemicellulose) levels and pectin methylesterase (PME) activity in roots and decreased the translocation of Al from the external environment to the cytoplasm by downregulating the expression of OsNRAT1, which responsible to encode an Al transporter protein Nrat1 (Nramp aluminum transporter 1). The addition of PUT under Al toxicity conditions significantly inhibited ethylene emissions and suppressed the expression of genes involved in ethylene biosynthesis. Treatment with the ethylene precursor 1-aminocylopropane-1-carboxylic acid (ACC) significantly improved ethylene emission, inhibited root elongation, increased the Al accumulation in root tips and the root cell wall, and increased cell wall pectin and hemicellulose contents in both rice cultivars under Al toxicity conditions. The ethylene biosynthesis antagonist aminoethoxyvinylglycine (AVG, inhibitor of the ACC synthase) had the opposite effect and reduced PME activity. Together, our results show that PUT decreases the cell wall Al contents by suppressing ethylene emissions and decreases the symplastic Al levels by downregulating OsNRAT1 in rice.


Assuntos
Alumínio/toxicidade , Parede Celular/química , Etilenos/química , Oryza/química , Putrescina/química , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Plantas/metabolismo , Raízes de Plantas/química
15.
Thromb Haemost ; 119(5): 705-715, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30900221

RESUMO

A nonasaccharide (FG9) derived from natural fucosylated glycosaminoglycan (FG) is identified as a selective intrinsic factor Xase complex (FIXa-FVIIIa-Ca2+-phospholipid, FXase) inhibitor that possesses potential inhibition of venous thrombus in rats and shows negligible bleeding risk. The mechanism and molecular target of the nonasaccharide for intrinsic FXase inhibition were systematically investigated and compared with low molecular weight heparin (LMWH). Our results showed that FG9 dose-dependently inhibited FX activation by intrinsic FXase complex in a noncompetitive inhibition pattern, where the apparent affinity for FG9 was approximately 1.8-fold higher than that for LMWH. FG9 displayed no inhibitory effect on the activity of FIXa/phospholipid, and did not affect the decay rate of FVIIIa activity. FG9 reduced the apparent affinity of FIXa for FVIIIa in a dose-dependent manner, and accelerated the decay of intrinsic FXase complex activity. FG9 bound to FIXa with high affinity and the FIXa binding sites of FG9 were overlapped with that of LMWH, and the ability of FG-derived oligosaccharides to bind FIXa required the minimum 9 degrees of polymerization. FG9 derivatives were prepared and their structures were confirmed by one-dimensional/two-dimensional nuclear magnetic resonance. Structure-activity relationship studies showed that carboxy reduction significantly weakened its anti-FXase activity and binding affinity to FIXa, while the effects of carboxyl ethyl esterification and deacetylation were relatively weaker. Overall, our results suggest that the nonasaccharide FG9 strongly inhibits intrinsic FXase complex activity via binding to FIXa and disrupting FIXa-FVIIIa interactions, and the free carboxyl groups of FG9 are required for its potent anti-FXase activity.


Assuntos
Cisteína Endopeptidases/metabolismo , Proteínas de Neoplasias/metabolismo , Oligossacarídeos/farmacologia , Trombose Venosa/tratamento farmacológico , Animais , Dióxido de Carbono/química , Modelos Animais de Doenças , Fator IXa/metabolismo , Fator X/metabolismo , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Cinética , Espectroscopia de Ressonância Magnética , Proteínas de Neoplasias/antagonistas & inibidores , Oligossacarídeos/química , Oligossacarídeos/uso terapêutico , Ligação Proteica , Ratos , Relação Estrutura-Atividade
16.
Plant Physiol Biochem ; 135: 41-50, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30500517

RESUMO

Nitrogen (N) allocation in leaves affects plant photosynthesis-N relationship and adaptation to environmental fluctuations. To reveal the role of leaf N allocation in water deficit stress acclimation in rice, the plants were grown in infertile soil supplying with low N (0.05 g N·kg-1 soil) and high N (0.2 g N·kg-1 soil), and then imposed to water deficit stress (∼75% relative soil water content). We found that the proportion of leaf N allocated in the photosynthetic apparatus was significantly positive correlated with photosynthetic N-use efficiency (PNUE), and that N allocation in the carboxylation system and bioenergetics were the primary two limiting factors of PNUE under the conditions of high N and water deficit stress. PNUE was not significantly affected by water stress in low N condition, but markedly reduced in high N condition. Under low N condition, plants reduced N allocation in the light-harvesting system and increased soluble protein and free amino acids, or reduced N allocation in the cell wall to maintain PNUE under water deficit stress. Under high N, however, plants decreased N allocation in bioenergetics or carboxylation, but increased N allocation in non-photosynthetic components during water stress. Our results reveal that the coordination of leaf N allocation between photosynthetic and non-photosynthetic apparatus, and among the components of the photosynthetic apparatus is important for the trade-off between PNUE and the acclimation of water deficit stress in rice.


Assuntos
Nitrogênio/metabolismo , Oryza/metabolismo , Fotossíntese , Folhas de Planta/metabolismo , Aclimatação , Aminoácidos/metabolismo , Catalase/metabolismo , Clorofila/metabolismo , Desidratação , Malondialdeído/metabolismo , Oryza/crescimento & desenvolvimento , Oryza/fisiologia , Fotossíntese/fisiologia , Folhas de Planta/fisiologia , Prolina/metabolismo
17.
Plant Physiol Biochem ; 132: 189-201, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30212760

RESUMO

In plants, different forms of nitrogen (NO3- or NH4+) affect nutrient uptake and environmental stress responses. In the present study, we tested whether NO3- and NH4+ affect the ability of rice (Oryza sativa) to tolerate the toxic heavy metal cadmium (Cd). Compared with NO3-, NH4+ treatment significantly increased chlorophyll contents and reduced Cd2+ levels in rice cultivars Nipponbare (japonica) and Kasalath (indica) grown in 0.2 mM Cd2+. NH4+ significantly reduced the pectin and hemicellulose contents and inhibited the pectin methylesterase (PME) activity in rice roots, thereby reducing the negative charges in the cell wall and decreasing the accumulation of Cd2+ in roots. In addition, NH4+ reduced the absorption and root-to-shoot translocation of Cd2+ by decreasing the expression of OsHMA2 and OsNramp5 in the root. Levels of the signaling molecule putrescine were significantly higher in the roots of both rice cultivars provided with NH4+ compared with NO3-. The addition of putrescine reduced Cd2+ contents in both rice cultivars and increased the chlorophyll content in shoots by reducing root cell wall pectin and hemicellulose contents, inhibiting PME activity and suppressing the expression of OsHMA2 and OsNramp5 in the root. Taken together, these results indicate that NH4+ treatment alleviated Cd toxicity, enabling rice to withstand the noxious effects of Cd by modifying the cell wall Cd-binding capacity due to alterations of pectin and hemicellulose contents and Cd transport, processes induced by increasing putrescine levels. Our findings suggest methods to decrease Cd accumulation in rice by applying NH4+ fertilizers.


Assuntos
Compostos de Amônio/farmacologia , Cádmio/toxicidade , Parede Celular/metabolismo , Oryza/metabolismo , Putrescina/metabolismo , Parede Celular/efeitos dos fármacos , Nitratos/farmacologia , Oryza/efeitos dos fármacos , Pectinas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Brotos de Planta/efeitos dos fármacos , Brotos de Planta/metabolismo , Polissacarídeos/metabolismo
18.
Glycobiology ; 28(10): 754-764, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30016441

RESUMO

Plasma contact system is the initial part of both the intrinsic coagulation pathway and kallikrein-kinin pathway, which mainly involves three proteins: coagulation factor XII (FXII), prekallikrein (PK) and high-molecular weight kininogen. Fucosylated chondroitin sulfate (FCS) is a unique sulfated glycosaminoglycan (GAG) composed of a chondroitin sulfate-like backbone and sulfated fucose branches. The native FCS was preliminary found to cause undesired activation of the plasma contact system. How this unusual GAG functions in this process remains to be clarified. Herein, the relationship between its structure, plasma contact activation and its effects on the PK-FXII reciprocal activation loop were studied. The recalcification time assay indicated that the FCS at high concentration could be procoagulant which may be attributed to its contact activation activity. The structure-activity relationship study indicated that its high molecular weight and distinct fucose side chains are required for contact activation by FCS, although the sulfate substitution types of its side chains have less impact. In human plasma, the native FCSs potently induced FXII-dependent contact activation. However, in purified systems FCS did not significantly activate FXII per se or induce its autoactivation, whereas FCS significantly promoted the activation of PK by factor XIIa. Polysaccharide-protein interaction assays showed that FCS bound to PK with higher affinity than other contact system proteins. These data suggested that potent contact activation by FCS requires the positive feedback loop between PK and FXII. These findings contribute to better understanding of contact activation by complex GAG.


Assuntos
Sulfatos de Condroitina/sangue , Sulfatos de Condroitina/metabolismo , Fator XIIa/metabolismo , Cininogênios/metabolismo , Pré-Calicreína/metabolismo , Sulfatos de Condroitina/química , Fator XIIa/química , Humanos , Cininogênios/química , Pré-Calicreína/química , Relação Estrutura-Atividade
19.
Eur J Med Chem ; 154: 133-143, 2018 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-29787913

RESUMO

Fucosylated chondroitin sulfate (FCS), an unusual glycosaminoglycan with fucose side chains, is a promising anticoagulant agent. To assess the effect of its structure on anticoagulant activity, its derivatives with various degrees of fucosylation (DF), molecular weights (Mw) and sulfation patterns were prepared and characterized. Biological tests showed that their APTT (activated partial thromboplastin time) prolonging activity and intrinsic factor Xase complex (factor IXa-VIIIa-Ca2+-PL complex) inhibitory activity were both reduced in FCS derivatives with lower Mw and DF. However, FCSs with DF at least 16% resulted in greater heparin cofactor II (HCII)-dependent thrombin inhibitory activity in response to decreasing DF, and these activities did not depend on Mw (Mw > 5.2 kDa). Solution competition binding assay further suggested that modulating the DF of FCS derivatives might enhance inhibition of thrombin by activating HCII. These findings imply that FCS derivatives with suitable chain length and DF value may be novel anticoagulants by activating HCII.


Assuntos
Anticoagulantes/farmacologia , Sulfatos de Condroitina/farmacologia , Cofator II da Heparina/metabolismo , Trombina/antagonistas & inibidores , Anticoagulantes/química , Anticoagulantes/isolamento & purificação , Sulfatos de Condroitina/química , Sulfatos de Condroitina/isolamento & purificação , Relação Dose-Resposta a Droga , Cofator II da Heparina/química , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Trombina/metabolismo
20.
Eur J Med Chem ; 148: 423-435, 2018 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-29477075

RESUMO

Selective inhibition of the endogenous coagulation pathway is a promising strategy for developing new anticoagulants. Fucosylated glycosaminoglycan (FG), a structurally complex glycosaminoglycan, has distinct anticoagulant properties, especially the strong intrinsic factor Xase inhibitory activity that is recognized as a new target with potential physiological and therapeutic applications. Detailed knowledge of FG structures is necessary for developing a clinically effective intrinsic FXase inhibitor. However, challenges remain to elucidate FG structures as a basis for pharmaceutical development. Herein, using the highly selective ß-elimination method, oligosaccharides with regular structures were prepared from the depolymerization products. Analysis of oligosaccharides further confirmed the precise structural sequence of the FG. Furthermore, biological activity assay suggested that these pure homogeneous oligosaccharides, particularly an octasaccharide, exhibit strong inhibition of the intrinsic coagulation pathway by inhibiting human intrinsic factor Xase. Our finding is significant for discovery of a new class of anticoagulant agents as intrinsic factor Xase inhibitors.


Assuntos
Anticoagulantes/química , Fucose/química , Glicosaminoglicanos/química , Proteínas de Neoplasias/antagonistas & inibidores , Cisteína Endopeptidases , Inibidores Enzimáticos/química , Humanos , Fator Intrínseco , Estrutura Molecular , Oligossacarídeos
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