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1.
J Asian Nat Prod Res ; : 1-7, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33890531

RESUMO

Phytochemical investigation on the 90% EtOH extract of the seeds of Cipadessa cinerascensa led to the isolation of three new limonoids, cinerascenoids A-C (1-3). Structural elucidation of all the compounds were performed by spectral methods such as 1 D and 2 D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy. All the limonoids were in vitro evaluated for their antimicrobial activities against six pathogenic microorganisms. Limonoids 1 and 2 exhibited some activities against three Gram negative bacteria with MIC values less than 60 µg/ml.

2.
Aging (Albany NY) ; 132021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879635

RESUMO

Colorectal cancer (CRC), a common malignant tumor in the digestive tract, is a leading cause of cancer-related death. SPRY4 has been reported to act as a tumor suppressor gene in various tumors. This study aims to assess the role of SPRY4 in colorectal cancer (CRC) and uncover its underlying mechanisms. Firstly, the expression levels of SPRY4 were measured in CRC cell lines. SPRY4-overexpressing or silencing plasmids were transfected into CRC cells to regulate its expression level. CCK-8, colony formation, EdU assay, wound-healing and Transwell assays were performed to determine cell proliferation, invasion and migration abilities. Then, apoptosis was measured by flow cytometry analysis, and the expression of apoptosis-related protein was analyzed by western-blotting. Next, the in vivo tumorigenesis assay was performed in nude mice. According to the results, there was a lower expression of SPRY4 in CRC cell lines compared with normal cell line, and the overexpression of SPRY4 significantly suppressed cell proliferation, migration and invasion, and promoted apoptosis in SW480 cells. Moreover, the enhanced proliferation, invasion and migration upon SPRY4 silencing was reversed by EZH2 inhibition. In addition, we found that the overexpression of SPRY4 inhibited tumorigenesis in vivo by diminishing the size and weight of the tumors. Our study indicates that SPRY4 might be a potential tumor suppressor gene and prognostic factor for patients with CRC.

3.
J Clin Nurs ; 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33829586

RESUMO

AIMS: To describe the specific domains of diabetes distress and factors associated with these domains. BACKGROUND: Diabetes distress is a common problem but not well recognised in adolescents by healthcare providers or adolescents themselves. There is insufficient evidence on how specific domains of diabetes distress exist in adolescents, making it challenging to select precise components to alleviate diabetes stress. DESIGN: A quantitative, descriptive and cross-sectional study. METHODS: Data were collected on socio-demographic and clinical characteristics, diabetes distress, perceived stress, self-efficacy and diabetes self-management using established questionnaires. Multivariate linear regression was conducted to examine the associations between specific factors and four domains in diabetes distress. STROBE checklist was used as the guideline for this study. RESULTS: A total of 100 adolescents with type 1 diabetes aged 12 to 18 years participated in this study. Adolescents experienced the highest levels of distress in the regimen-related distress [2.41 (SD =0.82)] and physician-related distress [2.40 (SD =0.80)] domains. Older age, female gender, more diabetes problem-solving and higher levels of perceived stress were associated with higher regimen-related distress (ß = 0.21 ~ 0.45, p < 0.05). Older age, female gender, a lower degree of endorsement of relevant diabetes-related goals and higher levels of perceived stress were associated with higher physician-related distress (ß = -0.29 ~ 0.34, p < 0.05). CONCLUSIONS: Diabetes distress was reported more on regimen-related and physician-related domains among adolescents with type 1 diabetes in China, associating with older age, female, increased perceived stress and poor diabetes-related problem-solving. RELEVANCE TO CLINICAL PRACTICE: Nurses need to screen the specific domains of diabetes distress among adolescents with type 1 diabetes, especially for the older adolescents and girls. This study highlighted the importance of incorporating diabetes-related problem-solving support and stress management strategies into diabetes management for adolescents with type 1 diabetes, which could help relieve diabetes distress.

4.
Molecules ; 26(8)2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33921211

RESUMO

Understanding the composition, function and regulation of complex cellular systems requires tools that quantify the expression of multiple proteins at their native cellular context. Here, we report a highly sensitive and accurate protein in situ profiling approach using off-the-shelf antibodies and cleavable fluorescent tyramide (CFT). In each cycle of this method, protein targets are stained with horseradish peroxidase (HRP) conjugated antibodies and CFT. Subsequently, the fluorophores are efficiently cleaved by mild chemical reagents, which simultaneously deactivate HRP. Through reiterative cycles of protein staining, fluorescence imaging, fluorophore cleavage, and HRP deactivation, multiplexed protein quantification in single cells in situ can be achieved. We designed and synthesized the high-performance CFT, and demonstrated that over 95% of the staining signals can be erased by mild chemical reagents while preserving the integrity of the epitopes on protein targets. Applying this method, we explored the protein expression heterogeneity and correlation in a group of genetically identical cells. With the high signal removal efficiency, this approach also enables us to accurately profile proteins in formalin-fixed paraffin-embedded (FFPE) tissues in the order of low to high and also high to low expression levels.

5.
Int J Mol Sci ; 22(8)2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33924609

RESUMO

Osmotic stress severely inhibits plant growth and development, causing huge loss of crop quality and quantity worldwide. Melatonin is an important signaling molecule that generally confers plant increased tolerance to various environmental stresses, however, whether and how melatonin participates in plant osmotic stress response remain elusive. Here, we report that melatonin enhances plant osmotic stress tolerance through increasing ROS-scavenging ability, and melatonin receptor CAND2 plays a key role in melatonin-mediated plant response to osmotic stress. Upon osmotic stress treatment, the expression of melatonin biosynthetic genes including SNAT1, COMT1, and ASMT1 and the accumulation of melatonin are increased in the wild-type plants. The snat1 mutant is defective in osmotic stress-induced melatonin accumulation and thus sensitive to osmotic stress, while exogenous melatonin enhances the tolerance of the wild-type plant and rescues the sensitivity of the snat1 mutant to osmotic stress by upregulating the expression and activity of catalase and superoxide dismutase to repress H2O2 accumulation. Further study showed that the melatonin receptor mutant cand2 exhibits reduced osmotic stress tolerance with increased ROS accumulation, but exogenous melatonin cannot revert its osmotic stress phenotype. Together, our study reveals that CADN2 functions necessarily in melatonin-conferred osmotic stress tolerance by activating ROS-scavenging ability in Arabidopsis.

6.
Clin Epigenetics ; 13(1): 87, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33883002

RESUMO

Diabetic kidney disease (DKD) is one of the most common microvascular complication of both type 1 (T1DM) and type 2 diabetes mellitus (T2DM), and the leading cause of end-stage renal disease (ESRD) worldwide. Persistent inflammation and subsequent chronic fibrosis are major causes of loss of renal function, which is associated with the progression of DKD to ESRD. In fact, DKD progression is affected by a combination of genetic and environmental factors. Approximately, one-third of diabetic patients progress to develop DKD despite intensive glycemic control, which propose an essential concept "metabolic memory." Epigenetic modifications, an extensively studied mechanism of metabolic memory, have been shown to contribute to the susceptibility to develop DKD. Epigenetic modifications also play a regulatory role in the interactions between the genes and the environmental factors. The epigenetic contributions to the processes of inflammation and fibrogenesis involved in DKD occur at different regulatory levels, including DNA methylation, histone modification and non-coding RNA modulation. Compared with genetic factors, epigenetics represents a new therapeutic frontier in understanding the development DKD and may lead to therapeutic breakthroughs due to the possibility to reverse these modifications therapeutically. Early recognition of epigenetic events and biomarkers is crucial for timely diagnosis and intervention of DKD, and for the prevention of the progression of DKD to ESRD. Herein, we will review the latest epigenetic mechanisms involved in the renal pathology of both type 1 (T1DN) and type 2 diabetic nephropathy (T2DN) and highlight the emerging role and possible therapeutic strategies based on the understanding of the role of epigenetics in DKD-associated inflammation and fibrogenesis.

7.
J Dermatol ; 2021 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-33896053

RESUMO

Verrucous epidermal nevus (VEN) is a benign skin disease that seriously affects appearance. Numerous therapeutic methods have been tried with varying results. However, there are few reports on the treatment of VEN by photodynamic therapy (PDT). This study aimed to evaluate the efficacy and adverse effects of 5-aminolevulinic acid (ALA)-PDT in VEN treatment with a long-term follow-up. A total of 16 patients with VEN received ALA-PDT and were followed up for more than 1 year to observe the treatment effects, adverse reactions, and patients' satisfaction. Complete improvement of lesions was observed in 11 patients (three to six sessions of ALA-PDT). Two patients obtained 90-99% improvement (five sessions) and 50-89% improvement in three patients (three to six sessions). They were satisfied with the treatment effects, with an average satisfaction of 4.19/5 (±0.91). Long-term follow-up ranging 14-50 months showed a low recurrence rate (2/16) and no scar left after ALA-PDT. The results demonstrate that ALA-PDT is an effective and safe therapy in treating VEN with mild adverse reactions and a low risk of scar formation.

8.
J Cell Physiol ; 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33843045

RESUMO

Diabetic nephropathy (DN) is the main cause of chronic kidney disease (CKD) and is one of the most common and serious complications of diabetes mellitus (DM). Sirtuin 1 (SIRT1) and tristetraprolin (TTP) are two important protective factors in DN; however, the regulatory relationship between SIRT1 and TTP, and the underneath mechanism are interesting but still unclear. Identifying the key factors that regulate SIRT1 or TTP may be of great value to the understanding and treatment of the DN. In this study, through systematic experimental methods, we found that the expression of miR-138 was significantly upregulated in DN clinical patient samples, and our experimental results suggested that miR-138 could bind the 3'-UTR of SIRT1 and inhibit its expression in both cultured podocytes and db/db mice kidney tissues. Furthermore, our in vitro and in vivo experiments also indicated miR-138 could target SIRT1 and affect TTP through p38 pathway. And downregulation of miR-138 attenuated podocyte injury and showed some extent of therapeutic effects in DN mice models. Our findings revealed that the regulatory axis of miR-138-SIRT1-p38-TTP might play a key role in DN. We believe that these findings may be of some value for deepening the understanding of DN and may serve as a reference for future treatment of this disease.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33810376

RESUMO

BACKGROUND: People with type 1 diabetes are susceptible to disordered eating behaviors. The American Diabetes Association recommends using the Diabetes Eating Problem Survey-Revised (DEPS-R) to screen them. There is no validated diabetes-specific screening measure in China. The objectives were to adapt DEPS-R into Mandarin Chinese and to test its psychometric properties among youths and adults with type 1 diabetes in China, respectively. METHODS: This study was conducted in two phases. Phase 1 included context relevance evaluation and instrument translation. Phase 2 was psychometric testing of reliability and construct validity among 89 youths (8~17 years old) and 61 adults with type 1 diabetes. RESULT: The Context Relevance Index and Translation Validity Index of this instrument were good. Strong internal consistency reliability correlations and convergent validity were demonstrated among youths and adults. DISCUSSION: The Chinese version of the DEPS-R is a valid and reliable tool for screening disordered eating behaviors in Chinese youths and adults with type 1 diabetes. The Context Relevance Index is advocated to evaluate the difference between the context in which an instrument was originally developed and the target context.


Assuntos
Diabetes Mellitus Tipo 1 , Adolescente , Adulto , China/epidemiologia , Diabetes Mellitus Tipo 1/epidemiologia , Humanos , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários
10.
Small ; : e2100560, 2021 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-33817963

RESUMO

Ruddlesden-Popper (RP) metal halide perovskites are considered as promising optoelectronic materials due to their good environmental stability and desirable optoelectronic properties. However, the phase composition and ordering in the deposited film, with a fixed ratio of large organic spacer cation in the precursor solution, are hard to be further tailored for specific optoelectronic applications. Herein, it is shown that even with a fixed spacer cation ratio, the phase composition and ordering can still be largely regulated by utilizing different crystallization kinetics of various cations with the inorganic octahedral lead halide. By using two different short cations to compete with the large spacer cation, the phase composition can be continuously tailored from thin multiple quantum wells (MQWs) dominated to 3D perovskite dominated. The phase ordering can be reversed from small n phases' prior to large n phases' prior near the substrate. Finally, with the same amount of large spacer cation protection, the perovskite can be tailored for both high-performance electroluminescence and photovoltaics with favorable energetic landscape for the corresponding desired first-order excitonic recombination and second-order free electron-hole recombination, respectively. This exploration substantially contributes to the understanding of precise phase engineering in RP perovskite and may provide a new insight into the design of multiple functional devices.

11.
Eur J Med Chem ; 218: 113401, 2021 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-33831779

RESUMO

Alzheimer's disease (AD) is the most common progressive neurodegenerative disorder characterized by neuronal loss and cognitive impairment that harshly affect the elderly individuals. Currently, the available anti-AD pharmacological approaches are purely symptomatic to alleviate AD symptoms, and the curative effects of novel anti-AD drugs focused on Aß target are disappointing. Hence, there is a tremendous need to adjust AD therapeutic targets and discover novel anti-AD agents. In AD, mitochondrial dysfunction gradually triggers neuronal death from different aspects and worsens the occurrence and progress of AD. Consequently, it has been proposed that the intervention of impaired mitochondria represents an attractive breakthrough point for AD treatments. Due to chemical diversity, poly-pharmacological activities, few adverse effects and multiple targeting, natural products (NPs) have been identified as a valuable treasure for drug discovery and development. Multiple lines of studies have scientifically proven that NPs display ameliorative benefits in AD treatment in relation to mitochondrial dysfunction. This review surveys the complicated implications for mitochondrial dysregulation and AD, and then summarizes the potentials of NPs and their underlying molecular mechanisms against AD via reducing or improving mitochondrial dysfunction. It is expected that this work may open the window to speed up the development of innovative anti-AD drugs originated from NPs and improve upcoming AD therapeutics.

12.
Lasers Med Sci ; 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33856584

RESUMO

In recent years, many researches have explored the diagnostic value of Raman spectroscopy in multiple types of tumors. However, as an emerging clinical examination method, the diagnostic performance of Raman spectroscopy in lung cancer remains unclear. Relevant diagnostic studies published before 1 June 2020 were retrieved from the Cochrane Library, PubMed, EMBASE, China National Knowledge Internet (CNKI), and WanFang databases. After the literature was screened, two authors extracted the data from eligible studies according to the inclusion and exclusion criteria. Obtained data were pooled and analyzed using Stata 16.0, Meta-DiSc 1.4, and RevMan 5.3 software. Fourteen diagnostic studies were eligible for the pooled analysis which includes 779 patients. Total pooled sensitivity and specificity of Raman spectroscopy in diagnosing lung cancer were 0.92 (95% CI 0.87-0.95) and 0.94 (95% CI 0.88-0.97), respectively. The positive likelihood ratio was 15.2 (95% CI 7.5-30.9), the negative likelihood ratio was 0.09 (95% CI 0.05-0.14), and the area under the curve was 0.97 (95 % CI 0.95-0.98). Subgroup analysis suggested that the sensitivity and specificity of RS when analyzing human tissue, serum, and saliva samples were 0.95 (95% CI 0.88-0.98), 0.97 (95% CI 0.89-0.99), 0.88 (95% CI 0.80-0.93), 0.87 (95% CI 0.78-0.92), 0.91 (95% CI 0.80-0.96), and 0.95 (95% CI 0.73-0.99), respectively. No publication bias or threshold effects were detected in this meta-analysis. This initial meta-analysis indicated that Raman spectroscopy is a highly specific and sensitive diagnostic technology for detecting lung cancer. Further investigations are also needed to focus on real-time detection using Raman spectroscopy under bronchoscopy in vivo. Moreover, large-scale diagnostic studies should be conducted to confirm this conclusion.

13.
Bioorg Chem ; 110: 104775, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33725509

RESUMO

The phytochemical investigation on the fruits of Clausena anisum-olens led to the isolation of 18 carbazole alkaloids (1-18), containing three new ones, clausenanisines A-C (1-3), and three new naturally occurring carbazole alkaloids, clausenanisines D-F (4-6), as well as 12 known analogues (7-18). The chemical structures of clausenanisines A-F (1-6) were elucidated by extensive spectroscopic methods. Notably, clausenanisine A (1) was a novel carbazole alkaloid with a unique five-membered cyclic ether, while clausenanisine E (5) is an unusual carbazole alkaloid owning an unprecedented naturally occurring carbon skeleton possessing 14 carbon atoms. The known carbazole alkaloids (7-18) were identified by the comparison of their spectral data with those data reported in the literature. All known carbazole alkaloids 7-18 were isolated from C. anisum-olens for the first time. Moreover, all isolated compounds 1-18 were assessed for their protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase inhibitory activities in vitro. Compounds 1-18 exhibited remarkable PTP1B inhibitory activities with IC50 values in the range of 0.58 ± 0.05 to 38.48 ± 0.32 µM, meanwhile, compounds 1-18 displayed significant α-glucosidase inhibitory activities with IC50 values ranging from 3.28 ± 0.16 to 192.23 ± 0.78 µM. These research results imply that the separation and identification of these carbazole alkaloids showing notable PTP1B and α-glucosidase inhibitory activities from the fruits of C. anisum-olens can be very significant for discovering and developing new PTP1B inhibitors and α-glucosidase inhibitors for the treatment of diabetes mellitus.

14.
Acta Pharmacol Sin ; 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33767379

RESUMO

Urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) are important targets for the development of uric acid-lowering drugs. We previously showed that the flexible linkers of URAT1 inhibitors could enhance their potency. In this study we designed and synthesized CDER167, a novel RDEA3710 analogue, by introducing a linker (methylene) between the naphthalene and pyridine rings to increase flexibility, and characterized its pharmacological and pharmacokinetics properties in vitro and in vivo. We showed that CDER167 exerted dual-target inhibitory effects on both URAT1 and GLUT9: CDER167 concentration-dependently inhibited the uptake of [14C]-uric acid in URAT1-expressing HEK293 cells with an IC50 value of 2.08 ± 0.31 µM, which was similar to that of RDEA3170 (its IC50 value was 1.47 ± 0.23 µM). Using site-directed mutagenesis, we demonstrated that CDER167 might interact with URAT1 at S35 and F365. In GLUT9-expressing HEK293T cells, CDER167 concentration-dependently inhibited GLUT9 with an IC50 value of 91.55 ± 15.28 µM, whereas RDEA3170 at 100 µM had no effect on GLUT9. In potassium oxonate-induced hyperuricemic mice, oral administration of CDER167 (10 mg·kg-1 · d-1) for 7 days was more effective in lowering uric acid in blood and significantly promoted uric acid excretion in urine as compared with RDEA3170 (20 mg·kg-1 · d-1) administered. The animal experiment proved the safety of CDER167. In addition, CDER167 displayed better bioavailability than RDEA3170, better metabolic stability and no hERG toxicity at 100 µM. These results suggest that CDER167 deserves further investigation as a candidate antihyperuricemic drug targeting URAT1 and GLUT9.

15.
Neuroimage ; 233: 117955, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33716155

RESUMO

Cerebrovascular reactivity (CVR) reflects the capacity of the brain to meet changing physiological demands and can predict the risk of cerebrovascular diseases. CVR can be obtained by measuring the change in cerebral blood flow (CBF) during a brain stress test where CBF is altered by a vasodilator such as acetazolamide. Although the gold standard to quantify CBF is PET imaging, the procedure is invasive and inaccessible to most patients. Arterial spin labeling (ASL) is a non-invasive and quantitative MRI method to measure CBF, and a consensus guideline has been published for the clinical application of ASL. Despite single post labeling delay (PLD) pseudo-continuous ASL (PCASL) being the recommended ASL technique for CBF quantification, it is sensitive to variations to the arterial transit time (ATT) and labeling efficiency induced by the vasodilator in CVR studies. Multi-PLD ASL controls for the changes in ATT, and velocity selective ASL is in theory insensitive to both ATT and labeling efficiency. Here we investigate CVR using simultaneous 15O-water PET and ASL MRI data from 19 healthy subjects. CVR and CBF measured by the ASL techniques were compared using PET as the reference technique. The impacts of blood T1 and labeling efficiency on ASL were assessed using individual measurements of hematocrit and flow velocity data of the carotid and vertebral arteries measured using phase-contrast MRI. We found that multi-PLD PCASL is the ASL technique most consistent with PET for CVR quantification (group mean CVR of the whole brain = 42±19% and 40±18% respectively). Single-PLD ASL underestimated the CVR of the whole brain significantly by 15±10% compared with PET (p<0.01, paired t-test). Changes in ATT pre- and post-acetazolamide was the principal factor affecting ASL-based CVR quantification. Variations in labeling efficiency and blood T1 had negligible effects.

16.
Nature ; 592(7854): 469-473, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33762731

RESUMO

Serotonin, or 5-hydroxytryptamine (5-HT), is an important neurotransmitter1,2 that activates the largest subtype family of G-protein-coupled receptors3. Drugs that target 5-HT1A, 5-HT1D, 5-HT1E and other 5-HT receptors are used to treat numerous disorders4. 5-HT receptors have high levels of basal activity and are subject to regulation by lipids, but the structural basis for the lipid regulation and basal activation of these receptors and the pan-agonism of 5-HT remains unclear. Here we report five structures of 5-HT receptor-G-protein complexes: 5-HT1A in the apo state, bound to 5-HT or bound to the antipsychotic drug aripiprazole; 5-HT1D bound to 5-HT; and 5-HT1E in complex with a 5-HT1E- and 5-HT1F-selective agonist, BRL-54443. Notably, the phospholipid phosphatidylinositol 4-phosphate is present at the G-protein-5-HT1A interface, and is able to increase 5-HT1A-mediated G-protein activity. The receptor transmembrane domain is surrounded by cholesterol molecules-particularly in the case of 5-HT1A, in which cholesterol molecules are directly involved in shaping the ligand-binding pocket that determines the specificity for aripiprazol. Within the ligand-binding pocket of apo-5-HT1A are structured water molecules that mimic 5-HT to activate the receptor. Together, our results address a long-standing question of how lipids and water molecules regulate G-protein-coupled receptors, reveal how 5-HT acts as a pan-agonist, and identify the determinants of drug recognition in 5-HT receptors.

17.
Bioorg Med Chem Lett ; 41: 127993, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33775841

RESUMO

Tranylcypromine (TCP)-based structural modifications lead to the discovery of new LSD1 inhibitors, of which compounds 26b and 29b effectively inhibit LSD1 with the IC50 values of 17 and 11 nM, respectively and also show good selectivity over MAO-B. Mechanistic studies showed that compound 29b concentration-dependently induced H3K4me1/2 accumulation in LSD1 overexpressed MGC-803 cells and also inhibited metastasis of MGC-803 cells. Collectively, both compounds could be promising lead compounds for further investigation.

18.
Int J Mol Sci ; 22(4)2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33669850

RESUMO

AP2 transcription factors play a crucial role in plant development and reproductive growth, as well as response to biotic and abiotic stress. However, the role of TaAP2-15, in the interaction between wheat and the stripe fungus, Puccinia striiformis f. sp. tritici (Pst), remains elusive. In this study, we isolated TaAP2-15 and characterized its function during the interaction. TaAP2-15 was localized in the nucleus of wheat and N. benthamiana. Silencing of TaAP2-15 by barley stripe mosaic virus (BSMV)-mediated VIGS (virus-induced gene silencing) increased the susceptibility of wheat to Pst accompanied by enhanced growth of the pathogen (number of haustoria, haustorial mother cells and hyphal length). We confirmed by quantitative real-time PCR that the transcript levels of pathogenesis-related genes (TaPR1 and TaPR2) were down-regulated, while reactive oxygen species (ROS)-scavenging genes (TaCAT3 and TaFSOD3D) were induced accompanied by reduced accumulation of H2O2. Furthermore, we found that TaAP2-15 interacted with a zinc finger protein (TaRZFP34) that is a homolog of OsRZFP34 in rice. Together our findings demonstrate that TaAP2-15 is positively involved in resistance of wheat to the stripe rust fungus and provides new insights into the roles of AP2 in the host-pathogen interaction.


Assuntos
Resistência à Doença , Doenças das Plantas/microbiologia , Fator de Transcrição AP-2/metabolismo , Triticum/metabolismo , Triticum/microbiologia , Sequência de Aminoácidos , Sequência de Bases , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Inativação Gênica/efeitos dos fármacos , Regiões Promotoras Genéticas/genética , Ligação Proteica/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Ácido Salicílico/farmacologia , Estresse Fisiológico/efeitos dos fármacos , Estresse Fisiológico/genética , Fator de Transcrição AP-2/química , Fator de Transcrição AP-2/genética , Triticum/efeitos dos fármacos , Triticum/genética
19.
J Atheroscler Thromb ; 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33678767

RESUMO

Abdominal aortic aneurysm (AAA) is a chronic inflammatory degenerative aortic disease, which particularly affects older people. Nucleotide-binding oligomerization domain-like receptor family protein 3 (NLRP3) inflammasome is a multi-protein complex and mediates inflammatory responses by activating caspase 1 for processing premature interleukin (IL)-1ß and IL-18. In this review, we first summarize the principle of NLRP3 inflammasome activation and the functionally distinct classes of small molecule NLRP3 inflammasome inhibitors. Next, we provide a comprehensive literature review on the expression of NLRP3 inflammasome effector mediators (IL-1ß and IL-18) and components (caspase 1, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and NLRP3) in clinical and experimental AAAs. Finally, we discuss the influence of genetic deficiency or pharmacological inhibition of individual effector mediators and components of NLRP3 inflammasome on experimental AAAs. Accumulating clinical and experimental evidence suggests that NLRP3 inflammasome may be a promise therapeutic target for developing pharmacological strategies for clinical AAA management.

20.
ACS Appl Mater Interfaces ; 13(11): 12888-12898, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33715358

RESUMO

With the gradual deep understanding of the tumorigenesis and development process, nanodrug are thought to have great prospects for individualized treatment of tumors. To deliver adequate concentration of active ingredients to targeted tissues, proteins are usually used as carriers to avoid clearance by the immune system. Herein, a new strategy is developed for preparation of the protein-functionalized targeting nanodrugs; different kinds of proteins (albumin, horseradish, transferrin, and ricin) can be quickly loaded in polyacrylic acid nanohydrogels (PAA-NGs) without discrimination within 1 min under the strong driving force of entropy; and the loading efficiency can reach 99% with about 50% loading content. Meanwhile, the activity of the released protein can be well retained. After oriented binding of the targeting agent on the surface of the nanocarriers by a unique and facile technique, the protein-loaded nanodrug exhibits excellent tumor cell uptake and targeting effect. The excellent targeting ability from the oriented binding is further proved by comparing with the non-oriented targeting system. With quick loading of the anti-tumor protein of ricin and oriented binding of transferrin protein (Tf), the targeting nanodrug (PAA-BB@Ricin/Tf) shows a remarkable anti-tumor effect. This study proves a new universal delivery and targeting strategy for improving the nanodelivery system, which has great potentials for clinical application.

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