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Three novel diterpenoid alkaloids, comprising two C19 -diterpenoid alkaloids (1 and 2) and one C20 -diterpenoid alkaloid (3), were isolated from Delphinium ajacis, alongside the six known compoundsâ (4-9). Their structures were elucidated by spectroscopic methods (MS, UV, IR, 1D and 2D NMR) and chemical properties. Simultaneously, the anti-inflammatory properties of all compoundsâ (1-9) was conducted, focusing on nitric oxide (NO) production in LPS-induced BV-2 cells. The results indicated compoundsâ 1-3, 7, and 8 have potential anti-inflammatory activity.
Assuntos
Alcaloides , Delphinium , Diterpenos , Delphinium/química , Espectroscopia de Ressonância Magnética , Alcaloides/farmacologia , Alcaloides/química , Diterpenos/farmacologia , Diterpenos/química , Anti-Inflamatórios/farmacologia , Estrutura MolecularRESUMO
Lysidrhodosides A-I (1-9), nine acylphloroglucinol glucoside derivatives along with three known analogues (10-12) were isolated from the leaves of Lysidice rhodostegia. Their structures and absolute configuration were elucidated by spectroscopic data analysis (NMR, UV, IR, HR-ESI-MS), single-crystal X-ray diffraction, and acid hydrolysis with HPLC analysis. Notably, compounds 7-9 represent the first examples of 3-methylbutyryl phloroglucinol glucoside dimers isolated from this plant. Additionally, compounds 1-12 were assessed for their inhibitory effects on nitric oxide (NO) in the LPS-induced BV-2 cells. The results showed that compounds 6 and 12 significantly inhibited the production of the inflammatory mediator NO, with an inhibitory rate of 95.96 and 91.13% at a concentration of 50 µM, respectively.
Assuntos
Fabaceae , Glucosídeos , Glucosídeos/farmacologia , Estrutura Molecular , Floroglucinol/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Espectroscopia de Ressonância Magnética , Fabaceae/química , Óxido NítricoRESUMO
Nav1.7, one of tetrodotoxin-sensitive voltage-gated sodium channels, mainly expressed in the small diameter dorsal root ganglion (DRG) neurons. The expression and accumulation on neuronal membrane of Nav1.7 increased following peripheral tissue inflammation or nerve injury. However, the mechanisms for membrane accumulation of Nav1.7 remained unclear. We report that KIF5b, a highly expressed member of the kinesin-1 family in DRGs, promoted the translocation of Nav1.7 to the plasma membrane in DRG neurons of the rat. Following nociceptive behaviors in rats induced by peripheral spared nerve injury (SNI), synchronously increased KIF5b and Nav1.7 expressions were observed in DRGs. Immunohistochemistry staining demonstrated the co-expressions of KIF5b and Nav1.7 in the same DRG neurons. Immunoprecipitation experiments further confirmed the interactions between KIF5b and Nav1.7. Moreover, intrathecal injections of KIF5b shRNA moderated the SNI-induced both mechanical and thermal hyperalgesia. The rescued analgesic effects also alleviated SNI-induced anxiety-like behaviors. In sum, KIF5b was required for the membrane localizations of Nav1.7, which suggests a novel mechanism for the trafficking of Nav1.7 involved in neuropathic pain.
Assuntos
Neuralgia , Traumatismos dos Nervos Periféricos , Ratos , Animais , Gânglios Espinais , Ratos Sprague-Dawley , Neuralgia/metabolismo , Neurônios/metabolismo , HiperalgesiaRESUMO
BACKGROUND: During left-sided cardiac valve surgery in patients with mild or no tricuspid regurgitation (TR), the tricuspid valve exploration plays a vital role in the decision-making of concomitant tricuspid annuloplasty. Currently lack of an appropriate standard to define tricuspid annular dilatation is a challenge. The aim of this study is to introduce and evaluate an alternative intraoperative method for Tricuspid Valve annuloplasty based on annular circumference that could trace the extent of annular dilatation and predict TR-progression, which can also guide the surgeons to intraoperative decision. METHODS: From January 2011 to December 2011, 131 patients (73 females, 58 males, and mean age 54±10.8) were selected for the study underwent left-sided cardiac valve surgery at Anzhen Hospital, all the subjects preoperatively diagnosed with non-significant TR. The enrolled subjects were followed-up over 5years for TR-progression. Tricuspid annular circumference (TAC) measurement was performed via special sizer for each patient, and the obtained values divided on the subject's body surface area (BSA) to achieve the tricuspid annular circumference index (TACI). The endpoint was set as the TR-progression by more than two grades, or a final TR grade ≥3+. RESULTS: The mean follow up period was 68±3.8 months (range, 60-77 months). In univariate, multivariate and logistic regression analysis three variables were noticed to be associated with TR progression, female gender (P<0.002), body mass index (BMI) (P<0.021), and intraoperatively measured TACI (P<0.001). But in multiple regression the TACI (OR 0.812; 95% CI: 0.748-0.883; P<0.001) was the single parameter which significantly related to TR-progression. Based on the receiver-operator curve (ROC), it was likely to derive an optimal cut-off 80.2 mm/m2 which could predict the postoperative development of TR with acceptable sensitivity and specificity 69%, 89%. CONCLUSIONS: Patients with mild or no TR undergoing left-sided valve surgery, intraoperative measurement of the TAC proved to be an ideal method to judge the tricuspid-annulus, it is capable to predict TR-progression. For prophylactic tricuspid repair a presumed TACI of 80.2 mm/m2 is recommended as an indicative threshold.
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BACKGROUND: Mobility and flexibility of anterior mitral leaflet (AML) are considered to be the important factor for mitral valve (MV) repair in rheumatic population, we try to use the bending angle of AML to quantify its' mobility and flexibility and investigate whether it can predict the success of rheumatic MV repair or not. METHODS: Total 54 patients underwent rheumatic MV surgeries with mild lesions of subvalvular apparatus from August, 2017 to November, 2017 at the author institution, we divided the patients into MV repair and MV replacement groups which included directly MV replacement and repair attempt but failed repairing transfer to replacement intraoperatively. Patients' MV structure was carefully evaluated on transthoracic echocardiography (TTE) and scored by the Wilkins score (WS) preoperatively. The bending angle of AML was measured during systole and diastole at different level before surgery. RESULTS: The differences of patients' demographic characteristics between repair group and replacement group were not statistically significant (P value >0.05) and the differences among B-angle, T-angle, Bs-angle, C-angle of AML between repair group and replacement groups were not statistically significant (P value >0.05). Only BT-angle in repair group was significantly larger than that of replacement group (21.56°±3.84°, 10.29°±6.02°, respectively, P<0.001), therefore the BT-angle was tested as a predictor of reparability by observing the receiver operating characteristic (ROC) curve (ROC area: 0.944, standard error: 0.06, 95% CI: 0.826-1), BT-angle of AML on preoperative transthoracic echo of 15.5° or more predicts feasibility of rheumatic MV repair with 100% sensitivity and 85.7% specificity in patients with mild lesions of subvalvular apparatus. Logistic regression for a single area of calcification (diameter <0.8 cm) at commissure were shown that: ß: 0.08, Exp (ß): 1.083, P: 0.777>0.05, the minor single calcified area at commissure had no effect on reparability of rheumatic MV disease. The differences of total WS and each component score between repair group and replacement group were not statistically significant (P value >0.05). By observing the ROC curve for total WS (ROC area: 0.508), the WS cannot be a predictor for the rheumatic MV repair. CONCLUSIONS: The bending angle of AML which was considered as quantification of mobility and flexibility of AML can be a predictor for MV repair in patients with rheumatic heart disease (RHD). The small single area of commissural calcification had no effect on reparability of rheumatic MV disease. WS cannot appropriately predict the outcome of rheumatic MV repair.
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BACKGROUND: Rheumatic heart disease (RHD) is a predominant health concern in developing countries. The aim of this meta-analysis was to evaluate the outcomes of mitral valve (MV) repair in patients with RHD, and identify predictors that may postoperatively affect treatment outcome. METHODS: A meta-analysis of eligible studies assessing patients undergoing MV repair with RHD and reporting the outcomes of MV repair, including 30-day mortality and long-term follow-up survival, MV reoperation rate and postoperative adverse events. Relevant English articles were searched up to 1 March, 2017 in Web of Science, PubMed, Google Scholar, Cochrane Library, EmBase, Elsevier, and Science Direct. Selected studies should meet all inclusion criteria, and underwent data extraction. RESULTS: A total of ten studies with 2,770 patients met all inclusion criteria, and were selected for assessment. Pooled analysis showed that 30-day mortality in patients with rheumatic MV disease after MV repair surgery was 1.9%, 95% confidence interval (CI) (0.8-2.9%); long-term survival was 97.3%, 95% CI (95.9-98.6%), and a freedom from reoperation rate of 93.6%, 95% CI (91.4-95.9%) was obtained; freedom from adverse events was 97.5%, 95% CI (95.2-99.8%). CONCLUSIONS: The outcome of rheumatic MV repair is outstanding in terms of low early mortality, high long-term survival and freedom from valve-related complications, which may be very common in patients after rheumatic MV replacement; meanwhile, MV reoperation rate after initial surgery is acceptable. Surgeons may try to repair MV in RHD when it is feasible.