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1.
Proc Natl Acad Sci U S A ; 118(48)2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34815339

RESUMO

Cytokinin (CK) in plants regulates both developmental processes and adaptation to environmental stresses. Arabidopsis histidine phosphotransfer ahp2,3,5 and type-B Arabidopsis response regulator arr1,10,12 triple mutants are almost completely defective in CK signaling, and the ahp2,3,5 mutant was reported to be salt tolerant. Here, we demonstrate that the arr1,10,12 mutant is also more tolerant to salt stress than wild-type (WT) plants. A comprehensive metabolite profiling coupled with transcriptome analysis of the ahp2,3,5 and arr1,10,12 mutants was conducted to elucidate the salt tolerance mechanisms mediated by CK signaling. Numerous primary (e.g., sugars, amino acids, and lipids) and secondary (e.g., flavonoids and sterols) metabolites accumulated in these mutants under nonsaline and saline conditions, suggesting that both prestress and poststress accumulations of stress-related metabolites contribute to improved salt tolerance in CK-signaling mutants. Specifically, the levels of sugars (e.g., trehalose and galactinol), amino acids (e.g., branched-chain amino acids and γ-aminobutyric acid), anthocyanins, sterols, and unsaturated triacylglycerols were higher in the mutant plants than in WT plants. Notably, the reprograming of flavonoid and lipid pools was highly coordinated and concomitant with the changes in transcriptional levels, indicating that these metabolic pathways are transcriptionally regulated by CK signaling. The discovery of the regulatory role of CK signaling on membrane lipid reprogramming provides a greater understanding of CK-mediated salt tolerance in plants. This knowledge will contribute to the development of salt-tolerant crops with the ability to withstand salinity as a key driver to ensure global food security in the era of climate crisis.

2.
Physiol Plant ; 173(4): 1682-1694, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34716914

RESUMO

Melatonin (MEL) is a ubiquitous molecule with pleiotropic roles in plant adaption to stress. In this study, we investigated the effects of foliar spray of 100 and 200 µM MEL on the biochemical and physiological traits linked with the growth performance of olive seedlings exposed to moderate (45 mM NaCl) and severe (90 mM NaCl) salinity. Both salt stress conditions caused a considerable reduction in leaf relative water content and the contents of photosynthetic pigments (carotenoids, chlorophylls a and b, and total chlorophylls), K+ and Ca+2 , while the contents of Na+ and the activities of antioxidant enzymes increased. In addition, salt-stressed olive seedlings showed high accumulations of hydrogen peroxide (H2 O2 ), malondialdehyde (MDA), and electrolyte leakage (EL), indicating that olive seedlings suffered from salinity-induced oxidative damage. In contrast, MEL application revived the growth of olive seedlings, including shoot height, root length and biomass under salt stress conditions. MEL protected the photosynthetic pigments and decreased the Na+ /K+ ratio under both moderate and severe salt stresses. Furthermore, MEL induced the accumulations of proline, total soluble sugars, glycine betaine, abscisic acid, and indole acetic acid in salt-stressed olive seedlings, which showed a positive correlation with improved leaf water status and biomass. MEL application also increased the activities of catalase, superoxide dismutase, ascorbate peroxidase, and peroxidase in salt-stressed seedlings, resulting in lower levels of H2 O2 , MDA, and EL in these plants. Taken together, MEL mitigates salinity through its roles in various biochemical and physiological processes, thereby representing a promising agent for application in crop protection.


Assuntos
Melatonina , Olea , Antioxidantes , Homeostase , Melatonina/farmacologia , Reguladores de Crescimento de Plantas , Salinidade , Plântula
3.
BMC Plant Biol ; 21(1): 442, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34587914

RESUMO

BACKGROUND: Stone-hardening stage is crucial to the development of grape seed and berry quality. A significant body of evidence supports the important roles of MicroRNAs in grape-berry development, but their specific molecular functions during grape stone-hardening stage remain unclear. RESULTS: Here, a total of 161 conserved and 85 species-specific miRNAs/miRNAs* (precursor) were identified in grape berries at stone-hardening stage using Solexa sequencing. Amongst them, 30 VvmiRNAs were stone-hardening stage-specific, whereas 52 exhibited differential expression profiles during berry development, potentially participating in the modulation of berry development as verified by their expression patterns. GO and KEGG pathway analysis showed that 13 VvmiRNAs might be involved in the regulation of embryo development, another 11 in lignin and cellulose biosynthesis, and also 28 in the modulation of hormone signaling, sugar, and proline metabolism. Furthermore, the target genes for 4 novel VvmiRNAs related to berry development were validated using RNA Ligase-Mediated (RLM)-RACE and Poly(A) Polymerase-Mediated (PPM)-RACE methods, and their cleavage mainly occurred at the 9th-11th sites from the 5' ends of miRNAs at their binding regions. In view of the regulatory roles of GA in seed embryo development and stone-hardening in grape, we investigated the expression modes of VvmiRNAs and their target genes during GA-induced grape seedless-berry development, and we validated that GA induced the expression of VvmiR31-3p and VvmiR8-5p to negatively regulate the expression levels of CAFFEOYL COENZYME A-3-O-METHYLTRANSFERASE (VvCCoAOMT), and DDB1-CUL4 ASSOCIATED FACTOR1 (VvDCAF1). The series of changes might repress grape stone hardening and embryo development, which might be a potential key molecular mechanism in GA-induced grape seedless-berry development. Finally, a schematic model of miRNA-mediated grape seed and stone-hardening development was proposed. CONCLUSION: This work identified 30 stone-hardening stage-specific VvmiRNAs and 52 significant differential expression ones, and preliminary interpreted the potential molecular mechanism of GA-induced grape parthenocarpy. GA negatively manipulate the expression of VvCCoAOMT and VvDCAF1 by up-regulation the expression of VvmiR31-3p and VvmiR8-5p, thereby repressing seed stone and embryo development to produce grape seedless berries.


Assuntos
Frutas/crescimento & desenvolvimento , Frutas/genética , Giberelinas/metabolismo , Sementes/crescimento & desenvolvimento , Sementes/genética , Transdução de Sinais/efeitos dos fármacos , Vitis/crescimento & desenvolvimento , Vitis/genética , Produtos Agrícolas/genética , Produtos Agrícolas/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento , Regulação da Expressão Gênica de Plantas , Genes de Plantas , MicroRNAs/genética , Vitis/metabolismo
4.
Bioorg Chem ; 116: 105363, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34555629

RESUMO

We have discovered a family of synthetic oxazole-based macrocycles to be active against SARS-CoV-2. The synthesis, pharmacological properties, and docking studies of the compounds are reported in this study. The structure of the new macrocycles was confirmed by NMR spectroscopy and mass spectrometry. Compounds 13, 14, and 15a-c were evaluated for their anti-SARS-CoV-2 activity on SARS-COV-2 (NRC-03-nhCoV) virus in Vero-E6 cells. Isopropyl triester 13 and triacid 14 demonstrated superior inhibitory activities against SARS-CoV-2 compared to carboxamides 15a-c. MTT cytotoxicity assays showed that the CC50 (50% cytotoxicity concentration) of 13, 14, and 15a-c ranged from 159.1 to 741.8 µM and their safety indices ranged from 2.50 to 39.1. Study of the viral inhibition via different mechanisms of action (viral adsorption, replication, or virucidal property) showed that 14 had mild virucidal (60%) and inhibitory effects on virus adsorption (66%) at 20 µM concentrations. Compound 13 displayed several inhibitory effects at three levels, but the potency of its action is primarily virucidal. The inhibitory activity of compounds 13, 14, and 15a-c against the enzyme SARS-CoV-2 Mpro was evaluated. Isopropyl triester 13 had a significant inhibition activity against SARS-CoV-2 Mpro with an IC50 of 2.58 µM. Large substituents on the macrocyclic template significantly reduced the inhibitory effects of the compounds. Study of the docking of the compounds in the SARS CoV-2-Mpro active site showed that the most potent macrocycles 13 and 14 exhibited the best fit and highest affinity for the active site binding pocket. Taken together, the present study shows that the new macrocyclic compounds constitute a new family of SARS CoV-2-Mpro inhibitors that are worth being further optimized and developed.


Assuntos
Antivirais/farmacologia , Proteases 3C de Coronavírus/antagonistas & inibidores , Descoberta de Drogas , Compostos Macrocíclicos/farmacologia , Oxazóis/farmacologia , Inibidores de Proteases/farmacologia , SARS-CoV-2/efeitos dos fármacos , Antivirais/síntese química , Antivirais/química , Proteases 3C de Coronavírus/metabolismo , Humanos , Compostos Macrocíclicos/síntese química , Compostos Macrocíclicos/química , Oxazóis/síntese química , Oxazóis/química , Inibidores de Proteases/síntese química , Inibidores de Proteases/química , SARS-CoV-2/enzimologia
5.
Bioorg Chem ; 116: 105302, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34464816

RESUMO

COX-2 selective drugs have been withdrawn from the market due to cardiovascular side effects, just a few years after their discovery. As a result, a new series of 1,5-diaryl pyrazole carboxamides 19-31 was synthesized as selective COX-2/sEH inhibitors with analgesic, anti-inflammatory, and lower cardiotoxic properties. The target compounds were synthesized and tested in vitro against COX-1, COX-2, and sEH enzymes. Compounds 20, 22 and 29 exhibited the most substantial COX-2 inhibitory activity (IC50 values: 0.82-1.12 µM) and had SIs of 13, 18, and 16, respectively, (c.f. celecoxib; SI = 8). Moreover, compounds 20, 22, and 29 were the most potent dual COX-2/sEH inhibitors, with IC50 values of 0.95, 0.80, and 0.85 nM against sEH, respectively, and were more potent than the standard AUDA (IC50 = 1.2 nM). Furthermore, in vivo studies revealed that these compounds were the most active as analgesic/anti-inflammatory derivatives with a good cardioprotective profile against cardiac biomarkers and inflammatory cytokines. Finally, the most active dual inhibitors were docked inside COX-2/sEH active sites to explain their binding modes.

6.
Bioorg Chem ; 112: 104960, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34020242

RESUMO

New EGFR inhibitor series of fifteen 5-chloro-3-hydroxymethyl-indole-2-carboxamide derivatives has been designed, synthesized, and tested for antiproliferative activity against a panel of cancer cell lines. The results showed that p-substituted phenethyl derivatives 10, 11, 13, 15 and 17-19 showed superior antiproliferative activity compared to their m-substituted counterparts 12, 14, 16 and 20. Compounds 15, 16, 19 and 20 displayed promising EGFR inhibitory activity as well as an increase in caspase 3 levels. Compounds 15 and 19 increased caspase-8 and 9 levels, as well as inducing Bax and decreasing Bcl-2 protein levels. Compound 19 demonstrated cell cycle arrest at pre-G1 and G2/M phases. The results of the docking study into the active site of EGFR revealed strong fitting of the new compounds with higher binding affinities compared to erlotinib.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Desenho de Fármacos , Inibidores de Proteínas Quinases/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Relação Estrutura-Atividade
7.
Molecules ; 26(5)2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33807861

RESUMO

Garlic (Allium sativum) is the second most important Allium crop that has been used as a vegetable and condiment from ancient times due to its characteristic flavor and taste. Although garlic is a sterile plant that reproduces vegetatively through cloves, garlic shows high biodiversity, as well as phenotypic plasticity and environmental adaptation capacity. To determine the possible mechanism underlying this phenomenon and to provide new genetic materials for the development of a novel garlic cultivar with useful agronomic traits, the metabolic profiles in the leaf tissue of 30 garlic accessions collected from different geographical regions, with a special focus on the Asian region, were investigated using LC/MS. In addition, the total saponin and fructan contents in the roots and cloves of the investigated garlic accessions were also evaluated. Total saponin and fructan contents did not separate the garlic accessions based on their geographical origin, implying that saponin and fructan contents were clone-specific and agroclimatic changes have affected the quantitative and qualitative levels of saponins in garlic over a long history of cultivation. Principal component analysis (PCA) and dendrogram clustering of the LC/MS-based metabolite profiling showed two major clusters. Specifically, many Japanese and Central Asia accessions were grouped in cluster I and showed high accumulations of flavonol glucosides, alliin, and methiin. On the other hand, garlic accessions grouped in cluster II exhibited a high accumulation of anthocyanin glucosides and amino acids. Although most of the accessions were not separated based on country of origin, the Central Asia accessions were clustered in one group, implying that these accessions exhibited distinct metabolic profiles. The present study provides useful information that can be used for germplasm selection and the development of new garlic varieties with beneficial biotic and abiotic stress-adaptive traits.


Assuntos
Frutanos/análise , Alho/genética , Alho/metabolismo , Metabolômica/métodos , Saponinas/análise , Aminoácidos/análise , Cromatografia Líquida , Análise por Conglomerados , Alho/fisiologia , Espectrometria de Massas , Folhas de Planta/anatomia & histologia , Folhas de Planta/fisiologia
8.
Crit Rev Biotechnol ; 41(6): 918-934, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33784900

RESUMO

Accumulation of reactive oxygen species (ROS), and their destructive effects on cellular organelles are the hallmark features of plants exposed to abiotic stresses. Plants are well-equipped with defensive mechanisms like antioxidant systems to deal with ROS-induced oxidative stress. Silicon has been emerged as an important regulator of plant protective mechanisms under environmental stresses, which can be up-taken from soil through a system of various silicon-transporters. In plants, silicon is deposited underneath of cuticles and in the cell wall, and help plant cells reduce deleterious effects of stresses. Furthermore, silicon can provide resistance to ROS-toxicity, which often accounts for silicon-mediated improvement of plant tolerance to different abiotic constraints, including salinity, drought, and metal toxicity. Silicon enhances the ROS-detoxification ability of treated plants by modulating the antioxidant defense systems, and the expression of key genes associated with oxidative stress mitigation and hormone metabolism. Silicon also displays additive roles in ROS-elimination when supplied with other external stimuli. Here, we discuss recent findings on how silicon is able to modulate antioxidant defense of plants in response to oxidative stress triggered by different abiotic constraints. We also review interactions of silicon with other signaling molecules, including nitric oxide, ROS, polyamines, and phytohormones in the mediation of plant protection against abiotic stress-induced oxidative damage.


Assuntos
Estresse Oxidativo , Silício , Plantas , Espécies Reativas de Oxigênio , Estresse Fisiológico
9.
Bioorg Chem ; 110: 104698, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33676043

RESUMO

We report herein design and synthesis of a new series of 3,7-bis-benzylidenes of ciprofloxacin. Most of the target compounds revealed good cytotoxic activity; the most potent 4e and 4i achieved strong broad spectrum antiproliferative activity with comparable activity to Doxorubicin with IC50 (µM) of 1.21 ± 0.02, 0.87 ± 0.04, 1.21 ± 0.02; 0.41 ± 0.02, 0.57 ± 0.06, 1.31 ± 0.04 and 1.26 ± 0.01, 1.79 ± 0.04, 0.63 ± 0.01 against leukemia cancer cell line HL-60 (TB), colon cancer cell line HCT-116 and breast cancer cell line MCF7, respectively. Moreover, the most potent derivative 4i induced apoptosis at G2/M phase Investigating the mechanism of action of compounds 4e, 4 h and 4i exhibited promising dual TOP Iα and TOP IIB % inhibition comparable to Camptothecin and Etoposide; respectively. Docking of 4e, 4 h and 4i into the active site of topo I and II proteins compared to Camptothein and Etoposide revealed acceptable binding score and augmented enzyme assay data. Hence, 4e and 4i are promising targeted antiproliferative dual acting TOP Iα TOP IIB inhibitors that require further optimization.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Ciprofloxacina/análogos & derivados , Ciprofloxacina/síntese química , Inibidores da Topoisomerase I/síntese química , Inibidores da Topoisomerase II/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ciprofloxacina/química , Ciprofloxacina/farmacologia , DNA Topoisomerases Tipo I/genética , DNA Topoisomerases Tipo I/metabolismo , DNA Topoisomerases Tipo II/genética , DNA Topoisomerases Tipo II/metabolismo , Desenho de Fármacos , Humanos , Modelos Moleculares , Estrutura Molecular , Proteínas de Ligação a Poli-ADP-Ribose/genética , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Conformação Proteica , Inibidores da Topoisomerase I/farmacologia , Inibidores da Topoisomerase II/farmacologia
10.
Physiol Plant ; 172(2): 334-350, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32797626

RESUMO

Exposure to drought stress negatively affects plant productivity and consequently threatens global food security. As global climates change, identifying solutions to increase the resilience of plants to drought is increasingly important. Several chemical treatments have recently emerged as promising techniques for various individual and combined abiotic stresses. This study shows compelling evidence on how acetic acid application promotes drought acclimation responses in soybean by investigating several morphological, physiological and biochemical attributes. Foliar applications of acetic acid to drought-exposed soybean resulted in improvements in root biomass, leaf area, photosynthetic rate and water use efficiency; leading to improved growth performance. Drought-induced accumulation of reactive oxygen species, and the resultant increased levels of malondialdehyde and electrolyte leakage, were considerably reverted by acetic acid treatment. Acetic acid-sprayed plants suffered less oxidative stress due to the enhancement of antioxidant defense mechanisms, as evidenced by the increased activities of superoxide dismutase, ascorbate peroxidase, catalase, glutathione peroxidase and glutathione S-transferase. Improved shoot relative water content was also linked to the increased levels of soluble sugars and free amino acids, indicating a better osmotic adjustment following acetic acid treatment in drought-exposed plants. Acetic acid also increased stem/root, leaf/stem and leaf/root mineral ratios and improved overall mineral status in drought-stressed plants. Taken together, our results demonstrated that acetic acid treatment enabled soybean plants to positively regulate photosynthetic ability, water balance, mineral homeostasis and antioxidant responses; thereby suggesting acetic acid as a cost-effective and easily accessible chemical for the management of soybean growth and productivity in drought-prone areas.


Assuntos
Antioxidantes , Secas , Aclimatação , Ácido Acético/farmacologia , Minerais , Osmorregulação , Fotossíntese , Soja , Estresse Fisiológico , Água
11.
Neuropsychopharmacology ; 46(2): 413-422, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33036015

RESUMO

The endocannabinoid system (eCBs) encompasses the endocannabinoids, their synthetic and degradative enzymes, and cannabinoid (CB) receptors. The eCBs mediates inhibition of neurotransmitter release and acts as a major homeostatic system. Many aspects of the eCBs are altered in a number of psychiatric disorders including schizophrenia, which is characterized by dysregulation of dopaminergic signaling. The GluN1-Knockdown (GluN1KD) and Dopamine Transporter Knockout (DATKO) mice are models of hyperdopaminergia, which display abnormal psychosis-related behaviors, including hyperlocomotion and changes in pre-pulse inhibition (PPI). Here, we investigate the ability of a novel CB1 receptor (CB1R) allosteric modulator, ABM300, to ameliorate these dysregulated behaviors. ABM300 was characterized in vitro (receptor binding, ß-arrestin2 recruitment, ERK1/2 phosphorylation, cAMP inhibition) and in vivo (anxiety-like behaviors, cannabimimetic effects, novel environment exploratory behavior, pre-pulse inhibition, conditioned avoidance response) to assess the effects of the compound in dysregulated behaviors within the transgenic models. In vitro, ABM300 increased CB1R agonist binding but acted as an inhibitor of CB1R agonist induced signaling, including ß-arrestin2 translocation, ERK phosphorylation and cAMP inhibition. In vivo, ABM300 did not elicit anxiogenic-like or cannabimimetic effects, but it decreased novelty-induced hyperactivity, exaggerated stereotypy, and vertical exploration in both transgenic models of hyperdopaminergia, as well as normalizing PPI in DATKO mice. The data demonstrate for the first time that a CB1R allosteric modulator ameliorates the behavioral deficits in two models of increased dopamine, warranting further investigation as a potential therapeutic target in psychiatry.


Assuntos
Canabinoides , Endofenótipos , Animais , Camundongos , Camundongos Knockout , Receptor CB1 de Canabinoide/genética , Receptores de Canabinoides , Roedores
12.
Bioorg Chem ; 107: 104522, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33317838

RESUMO

A potential microtubule destabilizing series of new thirty-five Pyrrol-2-one, Pyridazin-3(2H)-one and Pyridazin-3(2H)-one/oxime derivatives has been synthesized and tested for their antiproliferative activity against a panel of 60 human cancer cell lines. Compounds IVc, IVg and IVf showed a broad spectrum of growth inhibitory activity against cancer cell lines representing renal, cancer of lung, colon, central nervous system, ovary, and kidney. Among them, compound IVg was found to have broad spectrum anti-tumor activity against the tested nine tumor subpanels with selectivity ratios ranging between 0.21 and 3.77 at the GI50 level. In vitro assaying revealed tubulin polymerization inhibition by all active compounds IVc, IVg and IVf. The results of the docking study revealed nice fitting of compounds IVc, IVf, and IVg into CA-4 binding site in tubulin. The three compounds exhibited high binding affinities (ΔGb = -12.49 to -12.99 kcal/mol) toward tubulin compared to CA-4 (-8.87 kcal/mol). Investigation of the binding modes of the three compounds IVc, IVf, and IVg revealed that they interacted mainly hydrophobically with tubulin and similar binding orientations to that of CA-4. These observations suggest that tubulin is a possible target for these compounds.


Assuntos
Antineoplásicos/farmacologia , Piridazinas/farmacologia , Pirróis/farmacologia , Moduladores de Tubulina/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Ligação Proteica , Piridazinas/síntese química , Piridazinas/metabolismo , Pirróis/síntese química , Pirróis/metabolismo , Relação Estrutura-Atividade , Tubulina (Proteína)/química , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/síntese química , Moduladores de Tubulina/metabolismo
13.
Ther Clin Risk Manag ; 16: 1075-1080, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33204095

RESUMO

Objective: Developmental dysplasia of the hip (DDH) is an abnormal relationship between the acetabulum and the head of the femur. Plain x-ray of both hips at the age of 3 months is still in use in some countries. On plain films, classic lines and angles are evaluated to meet current guidelines for positive DDH. Among these is the acetabular angle (AA), which most did not exceed 30° in normal pelvis regardless of gender. A flat promontory gives the impression of a high AA angle, whereas a sharp promontory gives the impression of a low AA angle. Materials and Methods: All anteroposterior (AP) pelvic digital x-ray studies performed to rule out DDH were collected from the PACS systems. A novel angle was measured between a line parallel to the lateral aspect of the region of the inferior iliac spines and a line that extends along the acetabular roof to quantify the roundness of the iliac promontory. We called the former line the Miral line and the formed angle the iliac promontory angle. Results: We show that the promontory shape is significantly different between genders, and therefore it is mistaken to generalize an upper AA limit for males and females. In addition, we show that the current guideline of the upper limit of AA did not predict the incidence of DDH. Conclusion: We suggest that the current practice is introducing a high rate of false positive, especially among females, and the current guidelines on AA should be reviewed and assigned separately for males and females. This is more important for countries that did not utilize the ultrasonographic assessment for DDH.

14.
Molecules ; 25(22)2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33202886

RESUMO

Shallot landraces and varieties are considered an important genetic resource for Allium breeding due to their high contents of several functional metabolites. Aiming to provide new genetic materials for the development of a novel bulb onion cultivar derived from intraspecific hybrids with useful agronomic traits from shallots, the metabolic profiles in the bulbs of 8 Indonesian shallot landraces and 7 short-day and 3 long-day bulb onion cultivars were established using LC-Q-TOF-MS/MS. Principal component analysis, partial least squares discriminant analysis, and dendrogram clustering analysis showed two major groups; group I contained all shallot landraces and group II contained all bulb onion cultivars, indicating that shallots exhibited a distinct metabolic profile in comparison with bulb onions. Variable importance in the projection and Spearman's rank correlation indicated that free and conjugated amino acids, flavonoids (especially metabolites having flavonol aglycone), and anthocyanins, as well as organic acids, were among the top metabolite variables that were highly associated with shallot landraces. The absolute quantification of 21 amino acids using conventional HPLC analysis showed high contents in shallots rather than in bulb onions. The present study indicated that shallots reprogrammed their metabolism toward a high accumulation of amino acids and flavonoids as an adaptive mechanism in extremely hot tropical environments.


Assuntos
Flavonoides/análise , Metaboloma , Cebolas/química , Raízes de Plantas/química , Cebolinha Branca/química , Antocianinas/análise , Cromossomos de Plantas , Análise por Conglomerados , Análise Discriminante , Flavonóis/análise , Haploidia , Metabolômica , Cebolas/genética , Melhoramento Vegetal , Análise de Componente Principal , Cebolinha Branca/genética , Especificidade da Espécie , Espectrometria de Massas em Tandem
15.
Sci Rep ; 10(1): 17189, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33057205

RESUMO

Wheat (Tritium aestivum) is vulnerable to future climate change because it is predominantly grown under rain-fed conditions in drought-prone areas. Thus, in-depth understanding of drought effect on wheat metabolism is essential for developing drought-tolerant wheat varieties. Here, we exposed wheat 'Norin 61' plants to progressive drought stress [0 (before drought), 2, 4, 6, 8, and 10 days after withholding water] during the flowering stage to investigate physiological and metabolomic responses. Transcriptional analyses of key abscisic acid-responsive genes indicated that abscisic acid signalling played a major role in the adaptation of wheat to water deficit. Carbon isotope composition had a higher value than the control while canopy temperature (CT) increased under drought stress. The CT depression was tightly correlated with soil water potential (SWP). Additionally, SWP at - 517 kPa was identified as the critical point for increasing CT and inducing reactive oxygen species. Metabolome analysis identified four potential drought-responsive biomarkers, the enhancement of nitrogen recycling through purine and pyrimidine metabolism, drought-induced senescence based on 1-aminocyclopropane-1-carboxylic acid and Asn accumulation, and an anti-senescence response through serotonin accumulation under severe drought stress. Our findings provide in-depth insight into molecular, physiological and metabolite changes involved in drought response which are useful for wheat breeding programs to develop drought-tolerant wheat varieties.


Assuntos
Adaptação Fisiológica/fisiologia , Estresse Fisiológico/fisiologia , Triticum/metabolismo , Triticum/fisiologia , Ácido Abscísico/metabolismo , Aclimatação/fisiologia , Biomarcadores/metabolismo , Pão , Secas , Metaboloma/fisiologia , Nitrogênio/metabolismo , Melhoramento Vegetal/métodos , Espécies Reativas de Oxigênio/metabolismo , Solo , Água/metabolismo
16.
Bioorg Chem ; 104: 104260, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32920363

RESUMO

Recent studies have shown additive and synergistic effects associated with the combination of kinase inhibitors. BRAFV600E and EGFR are attractive targets for many diseases treatments and have been studied extensively. In keeping with our interest in developing anticancer targeting EGFR and BRAFV600E, a novel series of 2,3-dihydropyrazino[1,2-a]indole-1,4-dione has been rationally designed, synthesized and evaluated for their antiproliferative activity against a panel of four human cancer cell lines. Compounds 20-23, 28-31, and 33 showed promising antiproliferative activities. These compounds were further tested for their inhibitory potencies against EGFR and BRAFV600E kinases with erlotinib as a reference drug. Compounds 23 and 33 exhibited equipotency to doxorubicin against the four cell lines and efficiently inhibited both EGFR (IC50 = 0.08 and 0.09 µM, respectively) and BRAFV600E (IC50 = 0.1 and 0.29 µM, respectively). In cell cycle study of MCF-7 cell line, compounds 23 and 33 induced apoptosis and exhibited cell cycle arrest in both Pre-G1 and G2/M phases. Molecular docking analyses revealed that the new compounds can fit snugly into the active sites of EGFR, and BRAFV600E kinases. Compound 23, 31 and 33 adopted similar binding orientations and interactions to those of erlotinib and vemurafenib.


Assuntos
Antineoplásicos/farmacologia , Desenho de Fármacos , Indóis/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Pirazinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Humanos , Indóis/síntese química , Indóis/química , Simulação de Acoplamento Molecular , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Pirazinas/síntese química , Pirazinas/química , Relação Estrutura-Atividade
17.
J Med Radiat Sci ; 67(4): 277-283, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32578380

RESUMO

INTRODUCTION: Mammographic breast density is associated with a four to six times increased risk for breast cancer. Mammographic breast density varies by ethnicity, geographical region and age. The aim of this study was to document for the first time the mammographic breast density of Jordanian women and to explore its relationship with age. METHODS: Mammograms completed at King Abdullah University Hospital (Irbid, Jordan) between January 2016 and August 2018 were retrospectively reviewed and classified for breast density using the American College of Radiology (ACR) Breast Imaging-Reporting and Data System (BI-RADS). Descriptive analyses and Kurskal-Wallis test were used to examine the association between age and mammographic breast density. RESULTS: A total of 659 mammograms were reviewed. A significant inverse relationship was observed between age and breast density (P < 0.001). In women aged 40-49 years, 83.2% had dense breasts (ACR BI-RADS (c) and (d)). This percentage decreased to 59.8% of women aged 50-59 years; 38.4% of women in their 60s and 37.9% of women aged 70 years or older (ACR BI-RADS (c) only). CONCLUSION: The mammographic breast density of Jordanian women has been shown to be high across all age groups. Increased mammographic breast density is associated with increased breast cancer risk and renders mammography a less effective technique for the early detection of breast cancer. Breast cancer screening of Jordanian women should be individualised to develop screening protocols and include additional adjunct imaging to best manage women at high risk.


Assuntos
Densidade da Mama , Neoplasias da Mama/diagnóstico por imagem , Mamografia , Programas de Rastreamento , Adulto , Idoso , Feminino , Humanos , Jordânia , Pessoa de Meia-Idade
18.
Breast Cancer (Auckl) ; 14: 1178223420921381, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32523348

RESUMO

Purpose: To document the mammographic breast density (MBD) distribution of Jordanian women and the relationship with MBD with age. Correlation between breast cancer diagnosis and density was also explored. Methods: A retrospective review of 660 screening mammograms from King Abdullah University Hospital was conducted. Mammograms were classified into 2 groups: normal (return to routine screening) and breast cancer and rated using the American College of Radiology (ACR) Breast Imaging-Reporting and Data System (BI-RADS) 5th edition for MBD. The association between MBD and age was assessed by descriptive analyses and Kruskal-Wallis test. To compare between normal and breast cancer groups, chi-square post hoc tests with Bonferroni adjustment was used. Results: Groups consisted of 73.9% (n = 488) normal group and 26.1% (n = 172) breast cancer group. A significant inverse relationship was demonstrated between age and MBD among the normal (r = -.319, P < .01) and breast cancer group (r = -.569, P < .01). In total, 69% (n = 336) of women in the normal group and 71% (n = 122) in the breast cancer group and 79.1% (n = 159) of the normal group and 100% (n = 48) of the breast cancer group aged 40 to 49 years reported high MBD (ACR BI-RADS c or d). Conclusions: Most of women in both the normal and breast cancer groups evidenced increased MBD. Increased MBD was inversely proportional to age. As MBD has a known link to increased breast cancer risk and the decreased sensitivity of mammography and it is vital that future screening guidelines for Jordanian women consider the unique breast density distribution of this population.

19.
Plant Cell Physiol ; 61(8): 1399-1407, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32467978

RESUMO

Temperature is an essential physical factor that affects the plant life cycle. Almost all plant species have evolved a robust signal transduction system that enables them to sense changes in the surrounding temperature, relay this message and accordingly adjust their metabolism and cellular functions to avoid heat stress-related damage. Wheat (Triticum aestivum), being a cool-season crop, is very sensitive to heat stress. Any increase in the ambient temperature, especially at the reproductive and grain-filling stages, can cause a drastic loss in wheat yield. Heat stress causes lipid peroxidation due to oxidative stress, resulting in the damage of thylakoid membranes and the disruption of their function, which ultimately decreases photosynthesis and crop yield. The cell membrane/plasma membrane plays prominent roles as an interface system that perceives and translates the changes in environmental signals into intracellular responses. Thus, membrane lipid composition is a critical factor in heat stress tolerance or susceptibility in wheat. In this review, we elucidate the possible involvement of calcium influx as an early heat stress-responsive mechanism in wheat plants. In addition, the physiological implications underlying the changes in lipid metabolism under high-temperature stress in wheat and other plant species will be discussed. In-depth knowledge about wheat lipid reprograming can help develop heat-tolerant wheat varieties and provide approaches to solve the impact of global climate change.


Assuntos
Triticum/metabolismo , Resposta ao Choque Térmico/fisiologia , Temperatura , Termotolerância/fisiologia , Tilacoides/metabolismo
20.
Plant Cell Physiol ; 61(8): 1464-1476, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32374863

RESUMO

Phomopsis asparagi is one of the most serious fungal pathogens, which causes stem blight disease in Asparagus officinalis (AO), adversely affecting its production worldwide. Recently, the development of novel asparagus varieties using wild Asparagus genetic resources with natural P. asparagi resistance has become a priority in Japan due to the lack of resistant commercial AO cultivars. In this study, comparative metabolome and transcriptome analyses of susceptible AO and resistant wild Asparagus kiusianus (AK) 24 and 48 h postinoculated (AOI_24 hpi, AOI_48 hpi, AKI_24 hpi and AKI_48 hpi, respectively) with P. asparagi were conducted to gain insights into metabolic and expression changes associated with AK species. Following infection, the resistant wild AK showed rapid metabolic changes with increased levels of flavonoids and steroidal saponins and decreased asparagusic acid glucose ester content, compared with the susceptible AO plants. Transcriptome data revealed a total of 21 differentially expressed genes (DEGs) as the core gene set that displayed upregulation in the resistant AK versus susceptible AO after infection with P. asparagi. Kyoto Encyclopedia of Genes and Genomes pathway analysis of these DEGs identified 11 significantly enriched pathways, including flavonoid biosynthesis and primary metabolite metabolism, in addition to plant signaling and defense-related pathways. In addition, comparative single-nucleotide polymorphism and Indel distributions in susceptible AO and resistant AK plants were evaluated using the latest AO reference genome Aspof.V1. The data generated in this study are important resources for advancing Asparagus breeding programs and for investigations of genetic linkage mapping, phylogenetic diversity and plant defense-related genes.


Assuntos
Asparagus (Planta)/imunologia , Resistência à Doença , Phomopsis , Doenças das Plantas/imunologia , Asparagus (Planta)/genética , Asparagus (Planta)/metabolismo , Asparagus (Planta)/microbiologia , Resistência à Doença/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Metabolômica , Doenças das Plantas/microbiologia , Polimorfismo de Nucleotídeo Único/genética , Reação em Cadeia da Polimerase em Tempo Real
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