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1.
Exp Biol Med (Maywood) ; : 1535370220945987, 2020 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-32741216

RESUMO

IMPACT STATEMENT: The high mortality of non-small cell lung cancer (NSCLC) is mainly because the cancer has progressed to a more advanced stage before diagnosis. If NSCLC can be diagnosed at early stages, especially stage 0 or I, the overall survival rate will be largely improved by definitive treatment such as lobectomy. We herein validated two novel circulating serum ExmiRs as diagnostic biomarkers for early-stage NSCLC to fulfill the unmet medical need. Considering the number of specimens in this study, circulating serum exosomal miR-20b-5p and miR-3187-5p are putative NSCLC biomarkers, which need to be further investigated in a larger randomized controlled clinical trial.

2.
J Alzheimers Dis ; 2020 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-32741828

RESUMO

BACKGROUND: The inhibition of tau hyperphosphorylation is one of the most promising therapeutic targets for the development of Alzheimer's disease (AD) modifying drugs. Escitalopram, a kind of selective serotonin reuptake inhibitor antidepressant, has been previously reported to ameliorate tau hyperphosphorylation in vitro. OBJECTIVE: In this study, we determined whether escitalopram alleviates tau pathologies in the aged P301L mouse. METHODS: Mice were intraperitoneal injected with either escitalopram or saline for 4 weeks, and a battery of behavioral tests were conducted before tissue collection and biochemical analyses of brain tissue with western blot and immunohistochemistry. RESULTS: Wild-type (Wt) mice statistically outperformed the aged pR5 mice in the Morris water maze, while escitalopram treatment did not significantly rescue learning and memory deficits of aged pR5 mice. Tau phosphorylation at different phosphorylation sites were enhanced in the hippocampus of aged pR5 mice, while escitalopram treatment significantly decreased tau phosphorylation. The levels of phosphorylated GSK-3ß and phosphorylated Akt were significantly decreased in the hippocampus of aged pR5 mice, while escitalopram administration markedly increased the expression level. The aged pR5 mice showed significant decreases in PSD95 and PSD93, while the administration of escitalopram significantly increased PSD95 and PSD93 to levels comparable with the Wt mice. CONCLUSION: The protective effects of escitalopram exposure during advanced AD are mainly associated with significant decrease in tau hyperphosphorylation, increased numbers of neurons, and increased synaptic protein levels, which may via activation of the Akt/GSK-3ß signaling pathway.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32627045

RESUMO

PURPOSE: The purpose of this study was to analyse the risk factors associated with residual graft laxity after medial patellofemoral ligament reconstruction (MPFL-R) in patients with recurrent patellar dislocation (RPD). METHODS: A total of 312 consecutive patients (354 knees) with clinically diagnosed RPD who underwent MPFL-R from 2011 to 2015 were retrospectively analysed. Postoperative MPFL graft stability was assessed with patellofemoral stress radiography, and if the patellar central ridge surpassed the apex of the lateral femoral trochlea, the reconstructed MPFL was defined as having residual graft laxity. Finally, 15 patients who exhibited MPFL residual graft laxity (study group) were matched in a 1:2 fashion to 30 control participants (control group), who showed a normal postoperative patellar stability on stress radiography. Preoperative three-dimensional computed tomography (3D-CT) was used to identify patients with a high-grade J-sign. Femoral tunnel position was assessed using 3D-CT to identify cases with femoral tunnel malposition. Potential predictors of MPFL residual graft laxity, including age, sex, a preoperative high-grade J-sign, femoral tunnel malposition, and several radiological parameters, were assessed by logistic regression analysis. RESULTS: A preoperative high-grade J-sign was identified in 66.7% of the study group, which was significantly higher than that the 13.3% in the control group (P = 0.001). In addition, the presence of a preoperative high-grade J-sign (odds ratio, 11.9 [95% CI, 1.7-82.8]; P = 0.012) and femoral tunnel malposition (odds ratio, 8.2 [95% CI, 1.2-58.0]; P = 0.036) were determined to be independent risk factors associated with residual graft laxity after MPFL-R. CONCLUSION: The presence of a preoperative high-grade J-sign and femoral tunnel malposition are associated with residual graft laxity after MPFL-R in patients with RPD. These results may provide additional information for counselling patients on residual graft laxity after MPFL-R. LEVEL OF EVIDENCE: Level III.

4.
Med Res Rev ; 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32677056

RESUMO

The influenza pandemic continues to threaten public health due to its high morbidity and mortality rates, despite some successes in antiviral research. Natural drugs are important alternative therapies in the treatment of and recovery from influenza and have been the subjects of intense investigation during the last few decades. Many reports have shown that the development of novel bioactive chemicals extracted from natural drugs has significant advantages. Oseltamivir is a successful case of an anti-influenza drug synthesized using two natural products, quinic acid, and shikimic acid, as starting materials. In China, traditional Chinese medicine (TCM) plays an important role in the treatment of influenza. TCM herbal extracts and prescriptions or their isolated bioactive constituents have shown significant therapeutic and preventive effects against influenza. For example, the roots of Isatis indigotica (Banlangen) fight viral infection by targeting both the virus and the host and have significantly different effects than those of synthetic chemicals. Lianhuaqingwen capsule exerts its anti-influenza activity by regulating the immune response to interfere with both viral and host reactions and might well be an alternative therapeutic option to treat influenza virus infection. This paper reviews the chemical ingredients, crude extracts, and TCM prescriptions with anti-influenza activity reported during the period of 2010-September 2019. We hope that this comprehensive review will not only fuel research on anti-influenza active natural products and TCM research but also provide a promising alternative candidate for further anti-influenza drug development.

5.
Radiology ; 296(2): 393-400, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32484415

RESUMO

Background Collateral status assessed with single- or multiphase CT angiography can be used to predict outcome in patients with acute ischemic stroke (AIS); however, little is known about whether these measures could be comparable with CT perfusion parameters. Purpose To compare the predictive ability of collateral score systems assessed with single- or multiphase CT angiography and CT perfusion parameters in determining clinical outcomes in patients with AIS. Materials and Methods In this retrospective study, data obtained from October 2017 to August 2018 in consecutive patients with AIS caused by isolated anterior circulation large artery occlusion and that were obtained within 24 hours after onset were reviewed. The collateral score was assessed by using established scoring systems described by Menon et al. The correlations between single- and multiphase collateral scores, hypoperfusion, and ischemic core volume and final infarct volume (FIV) determined by follow-up diffusion-weighted imaging or unenhanced CT were studied. Receiver operating characteristic curves and multivariable logistic regression analysis were performed to assess the predictive ability of scoring systems and CT perfusion parameters for a favorable clinical outcome. Results A total of 119 patients (median age, 75 years; interquartile range, 66-82 years; 74 men) were included. Both single- and multiphase Menon scores had a moderate negative correlation with FIV (r = -0.43, P < .001; r = -0.44, P < .001). Receiver operating characteristic curve analysis revealed the multiphase Menon score performed better than the single-phase Menon score (area under the curve [AUC], 0.72 vs 0.64; P = .045) in the prediction of a favorable 90-day modified Rankin scale score. There was no difference between multiphase Menon score and hypoperfusion volume (AUC, 0.72 vs 0.72; P = .97) or ischemic core volume (AUC, 0.72 vs 0.71; P = .94). Multivariable analysis showed multiphase Menon score was an independent predictor of good clinical outcomes (odds ratio = 3.04, P = .001). Conclusion Multiphase Menon score performed better than single-phase Menon score and was comparable with CT perfusion parameters in determining clinical outcomes in patients with acute ischemic stroke. © RSNA, 2020.

6.
Zool Res ; 41(4): 381-394, 2020 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-32400977

RESUMO

Magnetic brain stimulation has greatly contributed to the advancement of neuroscience. However, challenges remain in the power of penetration and precision of magnetic stimulation, especially in small animals. Here, a novel combined magnetic stimulation system (c-MSS) was established for brain stimulation in mice. The c-MSS uses a mild magnetic pulse sequence and injection of superparamagnetic iron oxide (SPIO) nanodrugs to elevate local cortical susceptibility. After imaging of the SPIO nanoparticles in the left prelimbic (PrL) cortex in mice, we determined their safety and physical characteristics. Depressive-like behavior was established in mice using a chronic unpredictable mild stress (CUMS) model. SPIO nanodrugs were then delivered precisely to the left PrL cortex using in situ injection. A 0.1 T magnetic field (adjustable frequency) was used for magnetic stimulation (5 min/session, two sessions daily). Biomarkers representing therapeutic effects were measured before and after c-MSS intervention. Results showed that c-MSS rapidly improved depressive-like symptoms in CUMS mice after stimulation with a 10 Hz field for 5 d, combined with increased brain-derived neurotrophic factor (BDNF) and inactivation of hypothalamic-pituitary-adrenal (HPA) axis function, which enhanced neuronal activity due to SPIO nanoparticle-mediated effects. The c-MSS was safe and effective, representing a novel approach in the selective stimulation of arbitrary cortical targets in small animals, playing a bioelectric role in neural circuit regulation, including antidepressant effects in CUMS mice. This expands the potential applications of magnetic stimulation and progresses brain research towards clinical application.

7.
CNS Neurosci Ther ; 26(7): 720-729, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32243064

RESUMO

AIMS: Both amnestic mild cognitive impairment (aMCI) and remitted late-onset depression (rLOD) confer a high risk of developing Alzheimer's disease (AD). This study aims to determine whether the Characterizing AD Risk Events (CARE) index model can effectively predict conversion in individuals at high risk for AD development either in an independent aMCI population or in an rLOD population. METHODS: The CARE index model was constructed based on the event-based probabilistic framework fusion of AD biomarkers to differentiate individuals progressing to AD from cognitively stable individuals in the aMCI population (27 stable subjects, 6 progressive subjects) and rLOD population (29 stable subjects, 10 progressive subjects) during the follow-up period. RESULTS: AD diagnoses were predicted in the aMCI population with a balanced accuracy of 80.6%, a sensitivity of 83.3%, and a specificity of 77.8%. They were also predicted in the rLOD population with a balanced accuracy of 74.5%, a sensitivity of 80.0%, and a specificity of 69.0%. In addition, the CARE index scores were observed to be negatively correlated with the composite Z scores for episodic memory (R2  = .17, P < .001) at baseline in the combined high-risk population (N = 72). CONCLUSIONS: The CARE index model can be used for the prediction of conversion to AD in both aMCI and rLOD populations effectively. Additionally, it can be used to monitor the disease severity of patients.

8.
ACS Appl Mater Interfaces ; 12(18): 20849-20858, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32233356

RESUMO

Carbon dots (CDs) as new fluorescent materials with excellent fluorescence properties have shown enormous potential applications, especially in anticounterfeiting and cell imaging. Herein, nitrogen-doped CDs (NCDs) with excellent biocompatibility were prepared by a simple thermal sintering method. An extremely large red shift (∼130 nm) of the emission peak was observed when the excitation wavelength changes from 355 to 550 nm, indicating that NCDs are excellent fluorescent labeling materials for multiple cell imaging. On the other hand, NCDs showed obvious changes of emission intensity and peak position when the temperature increased from 223 to 323 K and the pH values changed from 1 to 13, respectively, which has been demonstrated by the "horse" pattern printed with NCD water-soluble fluorescent inks. The nontoxic NCDs dispersed in a multiple matrix are highly sensitive to excitation wavelength, temperature, and pH, indicating their great potential application in multiple anticounterfeiting and multiple cell imaging.

9.
Phytochemistry ; 175: 112372, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32305683

RESUMO

An undescribed iridoid (valeridoid A) and five undescribed bis-iridoids (valeridoids B-F), along with four known ones, were isolated from the roots and rhizomes of Valeriana jatamansi. Their structures were elucidated based on 1D and 2D NMR, as well as HRESIMS spectroscopic data. In addition, 8,9-didehydro-7-hydroxydolichodial and valeridoid F were found to inhibit the growth of three human glioma stem cells (GSC-3#, GSC-12# and GSC-18#).


Assuntos
Nardostachys , Valeriana , Humanos , Iridoides , Estrutura Molecular , Células-Tronco Neoplásicas , Raízes de Plantas
10.
Phytochemistry ; 175: 112373, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32305684

RESUMO

Twelve ent-isopimarane diterpenoids, including six undescribed ones, eupnerias J-O, were isolated from the stem barks of Euphorbia neriifolia L. Structurally, eupnerias J-M were the first examples of 18 (or 19)-norditerpenoid with ent-isopimarane skeleton from E. neriifolia. The absolute configuration of eupneria J was established based on the X-ray diffraction analysis and the experimental and calculated electronic circular dichroism (ECD), while the absolute configuration of eupnerias K-N were determined by the experimental and calculated ECD. In addition, the absolute configuration of the known compound, 3ß-hydroxysandaracopimaric acid, was determined by comparing its ECD spectrum with eupneria J, and renamed as eupneria P. Furthermore, eupneria J and eurifoloid H showed significant anti-HIV-1 activities with IC50 values of 0.31 and 6.70 µg/mL, respectively, and ent-isopimara-8(14),15-dien-3ß,12ß-diol possessed obvious anti-influenza virus activity against A/Puerto Rico/8/1934, with an IC50 at 3.86 µg/mL.


Assuntos
Diterpenos , Euphorbia , HIV-1 , Abietanos , Dicroísmo Circular , Estrutura Molecular
11.
Eur J Med Chem ; 194: 112253, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32222678

RESUMO

The prevention and control of plant diseases and insect pests is the most crucial issue facing crop protection. To discover novel pesticide candidates with diverse chemical structures from natural products, a series of luotonin A analogues were designed, synthesized and evaluated for their antifungal and insecticidal activities. Most of these compounds exhibited potent activity against Botrytis cinerea, Magnaporthe oryzae and Aphis craccivora. Among them, the antifungal activity of compound 10s against B. cinerea was comparable to azoxystrobin (EC50 = 0.09 mM) and against M. oryzae (EC50 = 0.19 mM) was slightly weaker than that of azoxystrobin (EC50 = 0.17 mM). Compounds 10k and 10o are the most active compounds against A. craccivora having identical mortality value of 42.05% at 50 µg/mL, respectively, which were slightly lower than pymetrozine (51.14%) at the same concentration. Revealed morphological changes of the fungal cell surface by scanning electron microscopy indicated that luotonin A analogues might exert their antifungal activity by destroying fungal cell membrane and cell wall. Furthermore, the results of the in vivo protective and curative activities of the compound 10s against S. sclerotiorum and B. cinerea showed that the curative effect was stronger than its protective effect and the curative effects reached 67.17% and 73.82% at 80 µg/mL respectively. The above results further demonstrated the potential of luotonin A analogues as novel fungicides and insecticides.

12.
CNS Neurosci Ther ; 26(4): 416-429, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32154670

RESUMO

INTRODUCTION: Clearance of damaged cells and debris is beneficial for the functional recovery after ischemic brain injury. However, the specific phagocytic receptor that mediates microglial phagocytosis after ischemic stroke is unknown. AIM: To investigate whether P2Y6 receptor-mediated microglial phagocytosis is beneficial for the debris clearance and functional recovery after ischemic stroke. RESULTS: The expression of the P2Y6 receptor in microglia increased within 3 days after transient middle cerebral artery occlusion. Inhibition of microglial phagocytosis by the selective inhibitor MRS2578 enlarged the brain atrophy and edema volume after ischemic stroke, subsequently aggravated neurological function as measured by modified neurological severity scores and Grid walking test. MRS2578 treatment had no effect on the expression of IL-1α, IL-1ß, IL-6, IL-10, TNF-α, TGF-ß, and MPO after ischemic stroke. Finally, we found that the expression of myosin light chain kinase decreased after microglial phagocytosis inhibition in the ischemic mouse brain, which suggested that myosin light chain kinase was involved in P2Y6 receptor-mediated phagocytosis. CONCLUSION: Our results indicate that P2Y6 receptor-mediated microglial phagocytosis plays a beneficial role during the acute stage of ischemic stroke, which can be a therapeutic target for ischemic stroke.

13.
Am J Sports Med ; 48(4): 838-846, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32058797

RESUMO

BACKGROUND: The lateral meniscus posterior root (LMPR) lesion further decreases dynamic knee stability after anterior cruciate ligament (ACL) injury owing to the loss of the "wedge effect" maintained by the posterior horn of the lateral meniscus. However, the effect of LMPR lesions on the static tibiofemoral relationship in extension after ACL injuries is not determined. PURPOSE: To (1) determine the effect of LMPR lesions on anterior tibial subluxation of the lateral compartment (ATSLC) in extension in patients with ACL injuries and to (2) identify the LMPR-related factors associated with excessive ATSLC in extension. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Between January 2015 and December 2017, 405 consecutive patients with diagnosed ACL injuries who underwent primary ACL reconstructions were retrospectively reviewed. Among them, 45 patients with combined ACL injuries and LMPR lesions (ACL+LMPR group) and 51 patients with isolated ACL injuries (ACL group) were identified. Values of ATSLC in extension were measured on preoperative supine magnetic resonance imaging and classified into high grade (≥6 mm) and low grade (<6 mm). The mean ATSLC in extension and the proportion of patients with high-grade ATSLC in extension were compared between the groups by univariate analysis. In the ACL+LMPR group, predictors of high-grade ATSLC in extension-including age, sex, body mass index, affected side, cause of injury, period from injury (<12 or ≥12 weeks), LMPR lesion pattern (radial tear or root avulsion), and meniscofemoral ligament integrity (intact or impaired)-were assessed by univariate analysis and multivariate logistic regression analysis. RESULTS: The mean ATSLC in extension in the ACL+LMPR group was significantly greater than that in the ACL group (5.6 mm vs 3.1 mm; P = .001). The proportion of patients with high-grade ATSLC in extension in the ACL+LMPR group was also significantly larger than that in the ACL group (44.4% vs 15.7%; P = .002). In addition, the root avulsion (instead of radial tear) (odds ratio, 28.750; 95% CI, 2.344-352.549; P = .009) and the period from injury ≥12 weeks (odds ratio, 17.095; 95% CI, 1.207-242.101; P = .036) were determined to be the 2 independent predictors of high-grade ATSLC in extension. However, age, sex, body mass index, affected side, cause of injury, and meniscofemoral ligament integrity were not. CONCLUSION: After ACL injuries, concomitant LMPR lesion further increased ATSLC in extension. Chronic LMPR avulsion was associated with high-grade ATSLC in extension.

14.
Am J Sports Med ; 48(3): 573-580, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32027514

RESUMO

BACKGROUND: Anterior tibial subluxation (ATS) in extension after anterior cruciate ligament (ACL) injury highlights an increased anterior position of the tibia relative to the femur. Recent studies demonstrated that subluxation is sometimes irreducible and the normal tibiofemoral relationship is not restored by ACL reconstruction (ACLR), which raises concerns regarding clinical outcomes after ACLR. HYPOTHESIS: Excessive preoperative ATS in extension is associated with inferior knee stability after anatomic ACLR. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: From March 2016 to January 2017, a total of 487 consecutive patients with clinically diagnosed noncontact ACL injuries who underwent primary anatomic ACLR were retrospectively analyzed. Of these patients, 430 met the criteria for inclusion in this study. Anterior subluxation of the lateral and medial compartments (ASLC and ASMC) in extension relative to the femoral condyles was measured on preoperative magnetic resonance imaging. Twenty patients (study group) who demonstrated excessive (>10 mm) ASLC and ASMC in extension were matched 1:2 to 40 participants (control group) who showed minimal or no (<3 mm) ASLC and ASMC in extension. The amount of ASLC and ASMC in extension relative to the femoral condyles at 2 years postoperatively was the primary outcome. Moreover, the Lysholm score, IKDC grade (International Knee Documentation Committee), and stability assessments (pivot-shift test and KT-1000 arthrometer side-to-side difference) were evaluated preoperatively and at the last follow-up visit. RESULTS: The preoperative mean ASLC and ASMC in extension of the study group were both significantly larger than those of the control group (study group vs control group: ASLC, 13.5 mm vs 1.2 mm; ASMC, 12.4 mm vs 1.0 mm; P < .05). Moreover, patients in the study group showed significantly larger posterior tibial slope than the patients in the control group (17.8°± 2.5° vs 9.5°± 1.5°; P < .05). At the final follow-up visit, the mean ASLC and ASMC of the study group were 8.1 mm and 7.3 mm, which were significantly larger than those of the control group (ASLC, 0.9 mm; ASMC, 0.7 mm; P < .05). In addition, the study group showed inferior knee stability when compared with the control group in terms of both the pivot-shift test (study group vs control group: 2 grade 2, 10 grade 1, and 8 grade 0 vs 1 grade 1 and 39 grade 0; P < .05) and the KT-1000 arthrometer side-to-side difference (study group vs control group: 4.4 ± 1.2 mm vs 1.5 ± 0.6 mm; P < .05). Furthermore, the study group showed significantly lower mean Lysholm score (study group vs control group: 80.3 ± 6.3 vs 93.3 ± 4.3, P < .05) and IKDC grading results (study group vs control group: 3 grade C, 16 grade B, and 1 grade A vs 3 grade B and 37 grade A; P < .05) as compared with the control group. CONCLUSION: In this short-term study, the excessive (>10 mm) preoperative ATS in extension after ACL injury was associated with inferior knee stability after anatomic ACLR.

15.
Chembiochem ; 21(9): 1341-1346, 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-31828918

RESUMO

In this work, we have identified a significantly improved variant (S131Y/Q252I) of the natural ϵ-keto ester reductase CpAR2 from Candida parapsilosis for efficiently manufacturing (R)-8-chloro-6-hydroxyoctanoic acid [(R)-ECHO] through co-evolution of activity and thermostability. The activity of the variant CpAR2S131Y/Q252I towards the ϵ-keto ester ethyl 8-chloro-6-oxooctanoate was improved to 214 U mg-1 -from 120 U mg-1 in the case of the wild-type enzyme (CpAR2WT )-and the half-deactivating temperature (T50 , for 15 min incubation) was simultaneously increased by 2.3 °C in relation to that of CpAR2WT . Consequently, only 2 g L-1 of lyophilized E. coli cells harboring CpAR2S131Y/Q252I and a glucose dehydrogenase (GDH) were required in order to achieve productivity similar to that obtained in our previous work, under optimized reaction conditions (530 g L-1 d-1 ). This result demonstrated a more economical and efficient process for the production of the key (R)-α-lipoic acid intermediate ethyl 8-chloro-6-oxooctanoate.

16.
Am J Sports Med ; 48(1): 117-127, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31765235

RESUMO

BACKGROUND: It has been speculated that the patellar J sign may have a negative effect on the clinical outcomes of patients with recurrent patellar dislocation (RPD). PURPOSE: To (1) evaluate clinical outcomes, postoperative patellar stability, and patellar maltracking correction in patients with RPD treated with derotational distal femoral osteotomy (DDFO) and combined procedures and (2) investigate the influence of J sign severity on the clinical outcomes. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Between January 2015 and December 2016, a total of 78 patients (81 knees) with RPD, a positive J sign, and an excessive femoral anteversion angle (FAA; ≥30°) were surgically treated with DDFO and combined procedures. J sign severity was graded according to a previously described classification system (grades 1-3). Routine radiography and computed tomography were performed on every patient to evaluate the patellar height, trochlear dysplasia, genu valgum, tibial tuberosity-trochlear groove distance, patellar lateral tilt angle, and patella-trochlear groove distance. The patellar lateral shift distance during stress radiography was measured preoperatively and postoperatively to quantify medial patellofemoral ligament (MPFL) graft laxity under anesthesia, and "MPFL residual graft laxity" was defined as the patellar ridge surpassing the apex of the lateral femoral trochlea. Patients were evaluated using the Kujala, International Knee Documentation Committee (IKDC), and Lysholm scores preoperatively and postoperatively. Patients were allocated into 3 subgroups in terms of the severity of the J sign: low-grade group 1 (grade 1; n = 19), low-grade group 2 (grade 2; n = 16), and high-grade group (grade 3; n = 12). Subgroup analyses were performed to investigate the influence of a high-grade J sign on the clinical outcomes. RESULTS: Among the 78 patients (81 knees), 47 patients (47 knees) met the inclusion criteria. The mean follow-up time was 26.1 ± 1.7 months. The mean preoperative and postoperative FAAs were 36.2°± 5.3° and 10.0°± 2.1°, respectively, with a mean correction angle of 26.2°± 5.9°. At the final follow-up, all patient-reported outcomes improved significantly, and subgroup analyses showed that the high-grade group had significantly lower Kujala scores (75.6 vs 85.3 for low-grade group 1 [P < .001] and 83.4 for low-grade group 2 [P = .001]), Lysholm scores (77.6 vs 84.6 for low-grade group 1 [P = .003]), and IKDC scores (78.6 vs 87.3 for low-grade group 1 [P = .001] and 84.3 for low-grade group 2 [P = .033]) than the low-grade groups. The total rate of MPFL residual graft laxity was 8.5% (4/47), and the prevalence of the postoperative residual J sign was 38.3% (18/47). Subgroup analyses showed significant differences between the high-grade group and the 2 low-grade groups with regard to the MPFL residual graft laxity rate (33.3% vs 0.0% for low-grade group 1 [P = .016] and 0.0% for low-grade group 2 [P = .024]), residual J sign rate (91.7% vs 15.8% for low-grade group 1 [P < .001] and 25.0% for low-grade group 2 [P < .001]), and patellar lateral shift distance (14.2 vs 8.1 mm for low-grade group 1 [P = .002] and 8.7 mm for low-grade group 2 [P = .007]). CONCLUSION: In a group of patients treated for RPD with a positive preoperative J sign and increased FAA (≥30°), patients with a preoperative high-grade J sign had inferior clinical outcomes, more MPFL residual graft laxity, and greater residual patellar maltracking.

17.
Eur J Med Chem ; 187: 111971, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31881457

RESUMO

For the purpose of advancing our research on diverse C-20 decorated derivatives of camptothecin (CPT), 46 new CPT acylthiourea derivatives were synthesized and evaluated in vitro for their cytotoxicity. All the compounds showed promising in vitro cytotoxicity against six tumor cell lines (Hep3B, MCF7, A549, MDA-MB-231, KB and KB-vin). Out of them, compound c20 possesses remarkable in vitro cytotoxic activity and is more potent than topotecan. Mechanistically, c20 not only induces cell cycle arrest and cell apoptosis in A549 cells, but also inhibits Topo I activity in the cell and cell-free system in a manner similar to that of topotecan. In both xenograft and primary HCC mouse models, c20 displays significant in vivo anti-cancer activity and is more potent than topotecan. In addition, the acute toxicity assay showed that c20 has no apparent toxicity to mouse liver, kidney and hemopoietic system of the FVB/N mice. Take together, these results indicated that compound c20 could be a potential anti-cancer candidate for further clinical trial.


Assuntos
Antineoplásicos/farmacologia , Camptotecina/farmacologia , Desenho de Fármacos , Ureia/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Camptotecina/síntese química , Camptotecina/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Estrutura Molecular , Relação Estrutura-Atividade , Células Tumorais Cultivadas , Ureia/análogos & derivados , Ureia/química
18.
Artigo em Inglês | MEDLINE | ID: mdl-31797022

RESUMO

PURPOSE: This study aimed at investigating the influence of an increased femoral anteversion angle on clinical outcomes after medial patellofemoral ligament reconstruction and combined tibial tubercle osteotomy for the treatment of recurrent patellar instability. It was hypothesized that an increased femoral anteversion is associated with inferior clinical outcomes. METHODS: From 2014 to 2016, a total of 144 consecutive patients with recurrent patellar instability were treated with medial patellofemoral ligament reconstruction and combined tibial tubercle osteotomy. The femoral anteversion angle was measured using three-dimensional computed tomography scans. Patients were allocated into group A (femoral anteversion < 20°), group B (femoral anteversion 20°-30°) and group C (femoral anteversion > 30°) based on the value of the femoral anteversion angle. Routine radiography and CT examinations were performed to evaluate the patellar height, trochlear dysplasia, genu valgum, and tibial tuberosity-trochlear groove (TT-TG) distance. The patellar lateral shift distance assessed with stress radiography was used pre- and postoperatively to quantify medial patellofemoral ligament residual laxity under anaesthesia. Patient-reported outcomes (Kujala, IKDC, and Lysholm scores) and patellar maltracking ("J-sign") were evaluated pre- and postoperatively. Finally, subgroup analysis was performed to investigate the influence of an increased femoral anteversion angle on the clinical and radiological outcomes. RESULTS: A total of 66 patients (70 knees) were included with a median follow-up time of 28 months (range 24-32). After a minimum of 2 years of follow-up, all patient-reported outcomes (Kujala, Lysholm, and IKDC scores) improved significantly, and subgroup analysis showed that group C had significantly lower Kujala scores (75 ± 8 vs. 84 ± 8, P13 = 0.003; 75 ± 8 vs. 82 ± 8, P23 = 0.030), Lysholm scores (81 ± 9 vs. 87 ± 7, P13 = 0.021) and IKDC scores (78 ± 6 vs. 85 ± 7, P13 = 0.001; 78 ± 6 vs. 84 ± 6, P23 = 0.005) than group A and group B. Twelve patients had a postoperative residual J-sign (17.1%), and significant differences were found between group C and group A regarding the rate of residual J-sign (32.1% vs. 4.8%, P13 = 0.003). Postoperatively, group C had a greater patellar lateral shift distance than group A (10 ± 4 vs. 6 ± 4 mm, P13 = 0.006) and group B (10 ± 4 vs. 6 ± 3 mm, P23 = 0.008). Additionally, patients with a residual J-sign demonstrated greater medial patellofemoral ligament laxity than patients without a residual J-sign (12 ± 4 vs. 9 ± 3 mm, P = 0.009). CONCLUSION: Patients with an increased femoral anteversion angle (> 30°) had inferior postoperative clinical outcomes, including greater patellar laxity, a higher rate of residual J-sign and lower patient-reported outcomes after medial patellofemoral ligament reconstruction and combined tibial tubercle osteotomy for the treatment of recurrent patellar instability. LEVEL OF EVIDENCE: III, retrospective cohort study.

19.
Chem Biodivers ; 16(12): e1900495, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31755643

RESUMO

Fifteen diterpenoids (1-15), including three undescribed ones with ent-atisane skeleton, eupnerias G-I (1-3), were obtained from Euphorbia neriifolia. Compounds 1-3 were established through comprehensive spectroscopic analysis. Compounds 4 and 5 exhibited obvious anti-HIV-1 effect, and their EC50 were 6.6±3.2 and 6.4±2.5 µg mL-1 , respectively. Compound 6 exhibited moderate cytotoxicity on HepG2 and HepG2/Adr cells with IC50 at 13.70 and 15.57 µm, respectively. In addition, compound 15 exhibited significant cytotoxicity on HepG2 cell lines (IC50 =0.01 µm), while it did not show any cytotoxicity against HepG2/Adr cell lines.


Assuntos
Fármacos Anti-HIV/química , Diterpenos/química , Euphorbia/química , Fármacos Anti-HIV/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Diterpenos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Euphorbia/metabolismo , HIV-1/efeitos dos fármacos , Humanos , Conformação Molecular , Relação Estrutura-Atividade
20.
Am J Physiol Renal Physiol ; 317(5): F1265-F1273, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31588798

RESUMO

Muscle wasting and diminished physical performance contribute to the morbidity and mortality of chronic kidney disease (CKD), for which no curative therapy exists. Accumulating evidence indicates that impaired angiogenesis occurs in the muscles of CKD models. Therefore, proangiogenesis therapy is considered a potentially effective strategy for limiting CKD-associated myopathy. Hypoxia-inducible factor (HIF)-prolyl hydroxylase inhibitor (HIF-PHI) stabilizes HIF and enhances muscle angiogenesis during acute ischemia; however, little evidence was available from CKD models. Here, we assessed whether pharmacological activation of HIF by MK-8617 (MK), a novel orally active HIF-PHI, improves CKD-associated myopathy. Mice were divided into sham or CKD groups, and CKD mice were subdivided into CKD + vehicle or MK treatment groups (1.5, 5, or 12.5 mg/kg for 12 wk). In CKD mice, skeletal muscle mass, mitochondrial amount, and exercise capacity decreased compared with sham mice. Compared with the CKD + vehicle group, low (1.5 mg/kg) and medium (5 mg/kg) doses of MK, but not the high dose (12.5 mg/kg), significantly restored these changes and was accompanied by incremental increases in HIF-1α. Furthermore, increased capillary density and area were observed in a MK dose-dependent manner, which is likely related to an improved VEGF response in the skeletal muscle of CKD mice. In addition, macrophage and proinflammatory cytokines, including monocyte chemoattractant protein 1, TNF-α, and IL-6, significantly increased in the high-dose MK group. These results indicate that HIF-PHI provides a potential therapeutic strategy to improve CKD-associated myopathy.


Assuntos
Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Doenças Musculares/tratamento farmacológico , Doenças Musculares/etiologia , Inibidores de Prolil-Hidrolase/farmacologia , Piridazinas/farmacologia , Pirimidinas/farmacologia , Insuficiência Renal Crônica/complicações , Administração Oral , Animais , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Força Muscular/efeitos dos fármacos , Músculo Esquelético/patologia , Doenças Musculares/patologia , Piridazinas/administração & dosagem , Pirimidinas/administração & dosagem
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