RESUMO
Sugar, as a nutrient exchange substance between arbuscular mycorrhizal (AM) fungi and host plants, plays an important role in the abiotic stress response of mycorrhizal plants. This experiment aimed to study the effects of AM fungi and phosphorus (P) addition on the sugar metabolism and 14-3-3 gene expression of Populus cathayana under drought stress. The results showed that drought affects the process of sugar metabolism by increasing the activities of amylase and invertase, resulting in the decrease of starch content in leaves and roots and the accumulation of soluble sugars (including reducing sugar and sucrose) in roots. Under drought stress, the activity or content of sucrose synthetase, sucrose phosphate synthase, acid invertase, alkaline invertase, reducing sugar, soluble sugar, sucrose, and starch in the root showed the best mycorrhizal effect at the 100 mg P level. The expression levels of the 14-3-3 genes (PcGRF10 and PcGRF11) were significantly increased by mycorrhizal induction under drought stress. These levels were positively correlated with SS, SPS, sucrose, and starch phosphorylase in leaves, as well as with almost all sugar metabolism indicators in roots. However, they were negatively correlated with starch content in both leaves and roots. Sugar metabolism and 14-3-3 protein gene expression were induced by AM fungi and P addition in response to drought stress. The 14-3-3 genes induced by AM fungi may be involved in participating in osmotic regulation during drought stress. This study provides a new idea for the mechanism of sugar metabolism of mycorrhizal plants in arid regions.
Assuntos
Micorrizas , Populus , Populus/genética , Proteínas 14-3-3/genética , Secas , beta-Frutofuranosidase , Sacarose , Fósforo , AmidoRESUMO
OBJECTIVES: We recently reported that percutaneous peripheral nerve stimulation (PNS or "neuromodulation") decreased pain and opioid consumption within the first two weeks following ambulatory surgery. However, the anatomic lead locations were combined for the analysis, and benefits for each location remain unknown. We therefore now report the effects of percutaneous PNS for brachial plexus and sciatic nerve leads separately. MATERIALS AND METHODS: Before surgery, leads were implanted percutaneously to target the brachial plexus (N = 21) for rotator cuff repair or sciatic nerve (N = 40) for foot/ankle surgery, followed by a single injection of local anesthetic. Postoperatively, subjects were randomized in a double masked fashion to 14 days of electrical stimulation (N = 30) or sham/placebo (N = 31) using an external pulse generator. The primary outcome of interest was opioid consumption and pain scores evaluated jointly. Thus, stimulation was deemed effective if superior on either outcome and at least noninferior on the other. RESULTS: For brachial plexus leads, during the first seven postoperative days pain measured with the numeric rating scale in participants given active stimulation was a median [interquartile range] of 0.8 [0.5, 1.6] versus 3.2 [2.7, 3.5] in patients given sham (p < 0.001). For this same group, opioid consumption in participants given active stimulation was 10 mg [5, 20] versus 71 mg [35, 125] in patients given sham (p = 0.043). For sciatic nerve leads, pain scores for the active treatment group were 0.7 [0, 1.4] versus 2.8 [1.6, 4.6] in patients given sham (p < 0.001). During this same period, participants given active stimulation consumed 5 mg [0, 30] of opioids versus 40 mg [20, 105] in patients given sham (p = 0.004). Treatment effects did not differ statistically between the two locations. CONCLUSIONS: Ambulatory percutaneous PNS of both the brachial plexus and sciatic nerve is an effective treatment for acute pain free of systemic side effects following painful orthopedic surgery.
Assuntos
Plexo Braquial , Estimulação Elétrica Nervosa Transcutânea , Humanos , Analgésicos Opioides/uso terapêutico , Projetos Piloto , Dor , Nervo IsquiáticoRESUMO
We pursued a structure-guided approach toward the development of improved dihydroorotate dehydrogenase (DHODH) inhibitors with the goal of forming new interactions between DHODH and the brequinar class of inhibitors. Two potential residues, T63 and Y356, suitable for novel H-bonding interactions, were identified in the brequinar-binding pocket. Analogues were designed to maintain the essential pharmacophore and form new electrostatic interactions through strategically positioned H-bond accepting groups. This effort led to the discovery of potent quinoline-based analogues 41 (DHODH IC50 = 9.71 ± 1.4 nM) and 43 (DHODH IC50 = 26.2 ± 1.8 nM). A cocrystal structure between 43 and DHODH depicts a novel water mediated H-bond interaction with T63. Additional optimization led to the 1,7-naphthyridine 46 (DHODH IC50 = 28.3 ± 3.3 nM) that forms a novel H-bond with Y356. Importantly, compound 41 possesses significant oral bioavailability ( F = 56%) and an elimination t1/2 = 2.78 h (PO dosing). In conclusion, the data supports further preclinical studies of our lead compounds toward selection of a candidate for early-stage clinical development.
Assuntos
Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/antagonistas & inibidores , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/química , Quinolinas/química , Administração Oral , Animais , Compostos de Bifenilo/química , Cristalografia por Raios X , Di-Hidro-Orotato Desidrogenase , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Inibidores Enzimáticos/síntese química , Feminino , Células HCT116 , Meia-Vida , Humanos , Ligação de Hidrogênio , Camundongos Endogâmicos , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/metabolismo , Piridinas/química , Pirimidinas/química , Solubilidade , Relação Estrutura-Atividade , TermodinâmicaRESUMO
OBJECTIVE: To explore an effective therapy for treatment of infantile febrile convulsion. METHODS: Seventy infants of febrile convulsion were randomly divided into two groups, a combined acupuncture and drug group (n = 36) were treated with Xingnao Kaiqiao needling method with Shuigou (GV 26) selected as main combined with intramuscular injection of luminal and intravenous perfusion of diazepam; and a drug group (n = 34) treated with simple intramuscular injection of luminal and intravenous perfusion of diazepam. Their therapeutic effects, the time of inducing the stopping convulsion, and the recurrence rate were investigated. RESULTS: The total effective rate was 86.1% in the combined acupuncture and drug group, better than 79.4% in the drug group (P<0.05), and the time of inducing the stopping convulsion in the combined acupuncture and drug group was shorter than that in the drug group (P<0.01), and the recurrence rate in the combined group was lower than that in the drug group (P<0.05). CONCLUSION: Acupuncture combined with intramuscular injection of luminal and intravenous perfusion of diazepam is an effective and safe method for febrile convulsion.