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2.
Korean J Radiol ; 2021 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-33938647

RESUMEN

OBJECTIVE: To investigate the prognostic value of preoperative cardiac magnetic resonance imaging (MRI) for long-term major adverse cardiac and cerebrovascular events (MACCEs) in patients undergoing tricuspid valve (TV) surgery for functional tricuspid regurgitation (TR). MATERIALS AND METHODS: The preoperative cardiac MR images, New York Heart Association functional class, comorbidities, and clinical events of 78 patients (median [interquartile range], 59 [51-66.3] years, 28.2% male) who underwent TV surgery for functional TR were comprehensively reviewed. Cox proportional hazards analyses were performed to assess the associations of clinical and imaging parameters with MACCEs and all-cause mortality. RESULTS: For the median follow-up duration of 5.4 years (interquartile range, 1.2-6.6), MACCEs and all-cause mortality were 51.3% and 23.1%, respectively. The right ventricular (RV) end-systolic volume index (ESVI) and the systolic RV mass index (RVMI) were higher in patients with MACCEs than those without them (77 vs. 68 mL/m², p = 0.048; 23.5 vs. 18.0%, p = 0.011, respectively). A high RV ESVI was associated with all-cause mortality (hazard ratio [HR] per value of 10 higher ESVI = 1.10, p = 0.03). A high RVMI was also associated with all-cause mortality (HR per increase of 5 mL/m² RVMI = 1.75, p < 0.001). After adjusting for age and sex, only RVMI remained a significant predictor of MACCEs and all-cause mortality (p < 0.05 for both). After adjusting for multiple clinical variables, RVMI remained significantly associated with all-cause mortality (p = 0.005). CONCLUSION: RVMI measured on preoperative cardiac MRI was an independent predictor of long-term outcomes in patients who underwent TV surgery for functional TR.

3.
Neurogastroenterol Motil ; : e14140, 2021 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-33939232

RESUMEN

BACKGROUND: The type 3 adenylyl cyclase (AC3) enzyme is involved in the synthesis of cyclic adenosine monophosphate (cAMP). It is primarily expressed in the central nervous system (CNS) and plays a crucial role in neurogenesis and neural dendritic arborization. However, the AC3's functional role in the gastrointestinal tract remains ambiguous. METHODS: AC3 expression in enteric tissue of AC3+/+ mice was investigated using immunohistochemistry and RT-PCR. AC3 knock-out mice (AC3-/- ) were used to examine the effect of AC3 on the enteric nervous system (ENS) function and the number of cilia and apoptotic cells. Additionally, total gastrointestinal transit time and colonic motility were compared between the AC3-/- and AC3+/+ groups of mice. KEY RESULTS: AC3 was predominately expressed in the myenteric plexus of the large intestine. Colonic-bead expulsion analysis showed accelerated propulsion in the large intestine of the AC3-/- mice. The AC3-/- mice demonstrated reduced nerve fibers and enteric glial cells count in colonic mucosa compared to the AC3+/+ mice. Furthermore, AC3-/- mice exhibited increased cellular apoptosis and reduced ARL13B+ cilium cells in the colonic lamina propria compared to the AC3+/+ mice. CONCLUSIONS: In AC3-/- mice, innervation of the lamina propria in the colonic mucosa was reduced and colonic propulsion was accelerated. AC3 is crucial for the development and function of the adult neural network of ENS. AC3 deficiency caused atrophy in the colonic mucosal neural network of mice.

4.
Int J Stroke ; : 17474930211012545, 2021 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-33877016

RESUMEN

BackgroundThere is an ongoing debate on the off-hour effect on endovascular treatment (EVT) for acute large vessel occlusion (LVO).AimsThis meta-analysis aimed to compare time metrics and clinical outcomes of acute LVO patients who presented/were treated during off-hour with those during working hours.Summary of reviewStructured searches on the PubMed, Embase, Web of Science, and Cochrane Library databases were conducted through February 23rd, 2021. The primary outcomes were onset to door, door to imaging, door to puncture, puncture to recanalization, procedural time, successful recanalization, symptomatic intracerebral hemorrhage (SICH), mortality in hospital, good prognosis (90-day modified Rankin Scale [mRS] score 0-2), and 90-day mortality. The secondary outcomes were imaging to puncture, onset to puncture, onset to recanalization, door to recanalization time, mRS 0-2 at discharge, and consecutive 90-day mRS score. The odds ratio (OR) and weighted mean difference (WMD) with 95% confidence interval (CI) of the outcomes were calculated using random-effect models. Heterogenicity and publication bias were analyzed. Subgroup and sensitivity analyses were conducted as appropriate.Nineteen studies published between 2014 and 2021 with a total of 14185 patients were eligible for quantitative synthesis. Patients in the off-hour group were significantly younger than those in the on-hour group and with comparable stroke severity and intravenous thrombolysis rate. The off-hour group had longer onset to door (WMD [95%CI], 12.83 [1.84-23.82] min), door to puncture (WMD [95%CI], 11.45 [5.93-16.97] min), imaging to puncture (WMD [95%CI], 10.39 [4.61-16.17] min), onset to puncture (WMD [95%CI], 25.30 [13.11-37.50] min), onset to recanalization (WMD [95%CI], 25.16 [10.28-40.04] min), and door to recanalization (WMD [95%CI], 18.02 [10.01-26.03] min) time. Significantly lower successful recanalization rate (OR [95%CI], 0.85 [0.76-0.95]; P=0.004; I2=0%) was detected in the off-hour group. No significant difference was noted regarding SICH and prognosis. But a trend towards lower OR of good prognosis was witnessed in the off-hour group (OR [95%CI], 0.92 [0.84-1.01]; P=0.084; I2=0%).ConclusionsPatients who presented/were treated during off-hour were associated with excessive delays before the initiation of EVT, lower successful reperfusion rate, and a trend towards worse prognosis when compared with working hours. Optimizing the workflows of EVT during off-hour is needed.

5.
Int J Biol Macromol ; 182: 639-647, 2021 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-33857508

RESUMEN

The present work aimed to assemble a simple, portable and economical L-junction microfluidic device to realize the adjustment and tunability of homogeneous round-shaped particles synthesis. In this study, we synthesize two kind of microparticles, including magnetic alginate microparticles (MAM) and chitosan-coated magnetic alginate (CMAM) used for controlling the drug release under a mild condition. Comparing to the traditional method, the MAM synthesized via this microfluidic approach has uniform size distribution, adjustable diameter as well as tunable magnetism. By exploring the amoxicillin as model drug, the MAM displays excellent pH-sensitive release, the effect of particle size on the drug release rate was investigated as well. The results show the smaller particles (220 µm) show a faster release rate than the bigger materials (1000 µm) due to their larger specific area, providing more frequency to interact with the reaction solution. The positive polyelectrolyte, chitosan, coated on the magnetic alginate surface endows CMAM time extension in drug release by two times, successfully achieving drug controlled and sustained release via the kinetics analysis. In summary, this microfluidic approach provides a convenient and efficient fluidic design for the well-controlled synthesis of micro-and nanoscale particles, which is a potential choice used for controlled and sustained drug release.

6.
Artículo en Inglés | MEDLINE | ID: mdl-33884548

RESUMEN

With the rapid promotion of new energy vehicles, in-use electric vehicle batteries (EVBs) are becoming an important component of urban mining. This paper analyzed the metal stocks in EVBs in China from 2009 to 2019 using a bottom-up method, which focused on the in-use stock of seven main metals, namely, nickel, cobalt, manganese, lithium, copper, aluminum, and iron, in primary use stage and secondary use stage of three EVB types, namely, lithium nickel manganese cobalt oxide battery (NMC), lithium iron phosphate battery (LFP), and lithium manganese oxide battery (LMO). It was found that the rapid development of electric vehicles (EVs) contributed to a dramatic increase in in-use metal stocks from 0.7 kt in 2009 to 1.1 Mt in 2019. To assess the increase, three scenarios simulating metal stocks in EVBs from 2020 to 2030 were analyzed, namely, baseline, NMC-dominated, and LFP-dominated, and results indicated that metal stocks will reach 20.6 Mt, 23.2 Mt, and 17.9 Mt, respectively, by 2030. Across the scenarios there is little proportional difference in metal stocks between the two use stages. The proportion of the three EVB types correlates to the development trend of EVB technology under each corresponding scenario. Besides, the in-use metal stocks in EVBs have high implied recycling potential and environmental benefit. The recycling potential of these seven metals is 1.0 Mt in 2019, and it will reach 20.0 Mt, 22.6 Mt, and 17.4 Mt, respectively, in 2030 under the three scenarios. The results reveal the current status and evolution characteristics of metal stocks in EVBs in China, and provide data for material flow analysis and life cycle management of EVBs.

7.
Nano Lett ; 2021 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-33825482

RESUMEN

Selective doping in semiconductors is essential not only for monolithic integrated circuity fabrications but also for tailoring their properties including electronic, optical, and catalytic activities. Such active dopants are essentially point defects in the host lattice. In atomically thin two-dimensional (2D) transition-metal dichalcogenides (TMDCs), the roles of such point defects are particularly critical in addition to their large surface-to-volume ratio, because their bond dissociation energy is relatively weaker, compared to elemental semiconductors. In this Mini Review, we review recent advances in the identifications of diverse point defects in 2D TMDC semiconductors, as active dopants, toward the tunable doping processes, along with the doping methods and mechanisms in literature. In particular, we discuss key issues in identifying such dopants both at the atomic scales and the device scales with selective examples. Fundamental understanding of these point defects can hold promise for tunability doping of atomically thin 2D semiconductor platforms.

8.
J Water Health ; 19(2): 267-277, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33901023

RESUMEN

The human gut harbors trillions of microbes, which are extremely important to the health of the host. However, the effect of drinking water on gut microbiota has been poorly understood. In this study, we explored the response of BALB/c mice gut bacterial community (feces) to the different types of drinking water, including commercial bottled mineral water (MW), natural water (NW), purified water (PW) and tap water (TW). Feces were cultured with brain heart infusion broth dissolved in four types of drinking water. 16S rRNA gene analysis was performed. Our results reveal that the microbiota composition is different among culturing with four types of drinking water. As the culture time increases, the number of OTUs significantly decreased, except under the aerobic condition of MW. Under aerobic conditions on the 5th day, the considerable differences of alpha diversity index are found between MW and three others, and these are the most unique taxa in the MW group. Importantly, the LEfSe analysis discovers that the Bacteroidetes taxa dominate the differences between MW and the other water types. Our findings demonstrate that the mineral water as a culture medium may lead to a progressive increase of the gut microbiota diversity by providing the growth convenience to Bacteroidetes.


Asunto(s)
Agua Potable , Microbiota , Animales , Heces , Ratones , Ratones Endogámicos BALB C , ARN Ribosómico 16S/genética
9.
Sensors (Basel) ; 21(6)2021 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-33799625

RESUMEN

Wind action is one of the environmental actions that has significant static and dynamic effects on long-span bridges. The lateral wind speed is the main factor affecting the lateral displacement of the main girder of the bridge. The main objective of the paper is to use the improved multi-rate fusion method to correct the monitoring data so that accurate correlation modeling of wind speed-displacement can be achieved. Two Kalman gain coefficients are introduced to improve the traditional multi-rate fusion method. The fusion method is verified by the results of simulated data analysis in time domain and frequency domain. Then, the improved multi-rate fusion method is used to fuse the monitoring lateral displacement and acceleration data of a bridge under strong wind action. The corrected lateral wind speed and displacement data is further applied to establish the correlation model through the linear regression. The improved multi-rate fusion method can overcome the inaccuracy of the high frequency stage of a Global Positioning System (GPS) sensor and the low frequency stage of acceleration sensor. The correlation coefficient of wind speed-displacement after fusion increases and the confidence interval width of regression model decreases, which indicates that the accuracy of the correlation model between wind speed and displacement is improved.

10.
Life (Basel) ; 11(3)2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33804020

RESUMEN

Chloranthus japonicus has been heavily investigated for the treatment of various diseases. This paper attempts to show that Chloranthus japonicus can modulate adipocyte differentiation of preadipocytes. To establish this, we investigated the effects of Chloranthus japonicus extract in peroxisome proliferator-activated receptor γ (PPARγ) expression, adipogenesis, and the underlying molecular mechanisms in C3H10T1/2 and 3T3-L1 cells. Our data showed that Chloranthus japonicus methanol extract increased lipid accumulation and promoted adipocyte differentiation. Further studies on the fractionation with various solvents led to the identification of Chloranthus japonicus hexane extract (CJHE) as the most potent inducer of adipocyte differentiation. CJHE consistently increased lipid accumulation and adipocyte marker expression including Pparγ and it acted during the early stages of adipocyte differentiation. Mechanistic studies revealed that CJHE and a Wnt inhibitor similarly stimulated adipogenesis and were active in Wnt-selective reporter assays. The effects of CJHE were inhibited by Wnt3a protein treatment and were significantly blunted in ß-catenin-silenced cells, further suggesting that CJHE acted on Wnt pathways to promote adipogenesis. We also showed that Chloranthus japonicus extracts generated from different plant parts similarly promoted adipocyte differentiation. These results identified Chloranthus japonicus as a pro-adipogenic natural product and suggest its potential use in metabolic syndrome.

11.
Biomedicines ; 9(3)2021 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-33805692

RESUMEN

Parkinson's disease (PD) is characterized by progressive dopaminergic neuron loss or dysfunction and is the second most prevalent neurodegenerative disorder after Alzheimer's disease. However, current therapeutic strategies for PD are limited to treating the outcomes of this disease rather than preventing it. Sinapic acid (SA) is a phenolic compound with potential antioxidant properties, which reportedly acts as a therapeutic agent against many diseases including cancer, as well as cardiac and liver diseases. However, little is known about the effects of SA against neurodegenerative disorders. Therefore, our study sought to evaluate the neuroprotective effects of non-cytotoxic concentrations of SA against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in SH-SY5Y human neuroblastoma cells, which we used as an in vitro PD model. SA increased cell viability and rescued the cells from 6-OHDA-induced apoptotic cell death. Additionally, oxidative stress responses were significantly blocked by SA, including reactive oxygen species (ROS) overproduction and decreased expression levels of antioxidant proteins. Notably, SA also attenuated mitochondrial dysfunction and endoplasmic reticulum (ER) stress. Moreover, SA dramatically inhibited the activation of mitogen-activated protein kinase (MAPK) proteins. Taken together, our findings highlight the potential PD prevention effects of SA, as well as its underlying mechanisms, making this compound a promising prevention and treatment agent for PD.

12.
Artículo en Inglés | MEDLINE | ID: mdl-33842953

RESUMEN

AIMS: To evaluate the impact of coronary artery calcium (CAC) score, minimal lumen area (MLA), and length of coronary artery stenosis on the diagnostic performance of the machine-learning-based computed tomography-derived fractional flow reserve (ML-FFR). METHODS AND RESULTS: In 471 patients with coronary artery disease, computed tomography angiography (CTA) and invasive coronary angiography were performed with fractional flow reserve (FFR) in 557 lesions at a single centre. Diagnostic performances of ML-FFR, computational fluid dynamics-based CT-FFR (CFD-FFR), MLA, quantitative coronary angiography (QCA), and visual stenosis grading were evaluated using invasive FFR as a reference standard. Diagnostic performances were analysed according to lesion characteristics including the MLA, length of stenosis, CAC score, and stenosis degree. ML-FFR was obtained by automated feature selection and model building from quantitative CTA. A total of 272 lesions showed significant ischaemia, defined by invasive FFR ≤0.80. There was a significant correlation between CFD-FFR and ML-FFR (r = 0.99, P < 0.001). ML-FFR showed moderate sensitivity and specificity in the per-patient analysis. Diagnostic performances of CFD-FFR and ML-FFR did not decline in patients with high CAC scores (CAC > 400). Sensitivities of CFD-FFR and ML-FFR showed a downward trend along with the increase in lesion length and decrease in MLA. The area under the curve (AUC) of ML-FFR (0.73) was higher than those of QCA and visual grading (AUC = 0.65 for both, P < 0.001) and comparable to those of MLA (AUC = 0.71, P = 0.21) and CFD-FFR (AUC = 0.73, P = 0.86). CONCLUSION: ML-FFR showed comparable results to MLA and CFD-FFR for the prediction of lesion-specific ischaemia. Specificities and accuracies of CFD-FFR and ML-FFR decreased with smaller MLA and long lesion length.

13.
Acc Chem Res ; 2021 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-33843190

RESUMEN

ConspectusMetal-organic frameworks (MOFs) are a huge, rapidly growing class of crystalline, porous materials that consist of inorganic nodes linked by organic struts. Offering the advantages of thermal stability combined with high densities of accessible reactive sites, some MOFs are good candidate materials for applications in catalysis and separations. Such MOFs include those with nodes that are metal oxide clusters (e.g., Zr6O8, Hf6O8, and Zr12O22) and long rods (e.g., [Al(OH)]n). These nanostructured metal oxides are often compared with bulk metal oxides, but they are in essence different because their structures are not the same and because the MOFs have a high degree of uniformity, offering the prospect of a deep understanding of reactivity that is barely attainable for most bulk metal oxides because of their surface heterogeneity. This prospect is being realized as it has become evident that adventitious components on MOF node surfaces, besides the linkers, are crucial. These ligands arise from modulators, solvents, or products of solvent decomposition in MOF synthesis solutions, and because they are minor components that are often irregularly placed on defects, they may not show up in X-ray diffraction (XRD) crystal structures. Hydroxyl groups on the nodes (like those on bulk metal oxides) are regarded as native functional groups arising from solvent water, but they may barely be present initially, with common ligands instead being formate and acetate formed from modulators formic acid and acetic acid. (Formate also arises from the decomposition of dimethylformamide (DMF) solvent.) Replacement and control of the node ligands is facilitated by postsynthesis reactions (e.g., with alcohols or aqueous HCl/H2SO4 solutions) or as a result of high-temperature decomposition. In catalysis, adventitious node ligands can be (a) reaction inhibitors that block active sites on the nodes (e.g., formate blocking Zr, Hf, or Al Lewis acid sites); (b) reaction intermediates (e.g., ethoxy in ethanol dehydration); or (c) active sites themselves (e.g., terminal OH groups in tert-butyl alcohol (TBA) dehydration). Surprisingly, in view of the catalytic importance of such ligands on bulk metal oxides, their subtle chemistry on MOF nodes is only recently being determined. We describe (1) methods for identifying and quantifying node ligands (especially by IR spectroscopy and by 1H NMR spectroscopy of MOFs digested in NaOH/D2O solutions); (2) node ligand surface chemistry expressed as reaction networks; (3) catalysis, with mechanisms and energetics determined by density functional theory (DFT) and spectroscopy; and (4) MOF unzipping by reactions of linker carboxylate ligands with reactants such as alcohols that break node-linker bonds, a cause of catalyst deactivation and also an indicator of node-linker bond strength and MOF stability.

14.
Artículo en Inglés | MEDLINE | ID: mdl-33907077

RESUMEN

PURPOSE: To report a rare case of Abiotrophia defectiva bleb associated endophthalmitis (BAE). METHODS: In this case report of a patient with BAE, the authors describe the features of severe and rapid onset, associated retinitis, and a favorable outcome after aggressive early intervention. RESULTS: A 75-year old female presented that decreased visual acuity of hand motions with elevated intraocular pressure of 39 mm Hg in the left eye. Her past ocular history was notable for severe primary open angle glaucoma with uneventful trabeculectomy and cataract surgery in both eyes 7 years prior. Examination revealed conjunctival injection and an opaque avascular cystic bleb along with anterior chamber cellular reaction with a B-scan ultrasound concerning for vitritis. Abiotrophia defectiva was isolated from the vitreous tap within 48 hours and confirmed later with 16S ribosomal RNA sequencing. After initial vitreous tap and inject and subsequent PPV, her BCVA had improved to 20/500 at post operative week 1 and then improved to 20/40 at post-operative month 2. Her exam was notable for resolved corneal edema, a deep and quiet anterior chamber, and resolved intraretinal hemorrhages. CONCLUSION: This is one of the first BAE cases with rapid identification of Abiotrophia defectiva. Abiotrophia defectiva was isolated from the initial vitreous tap within 48 hours and confirmed with 16S ribosomal RNA sequencing. This case highlights that rapid identification of Abiotrophia defectiva may be indicative of a greater bacterial load and should prompt aggressive intervention and that the visual prognosis can be favorable.

15.
Respir Res ; 22(1): 94, 2021 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-33789673

RESUMEN

BACKGROUND: Pneumonia is the most frequently encountered postoperative pulmonary complications (PPC) after orthotopic liver transplantation (OLT), which cause high morbidity and mortality rates. We aimed to develop a model to predict postoperative pneumonia in OLT patients using machine learning (ML) methods. METHODS: Data of 786 adult patients underwent OLT at the Third Affiliated Hospital of Sun Yat-sen University from January 2015 to September 2019 was retrospectively extracted from electronic medical records and randomly subdivided into a training set and a testing set. With the training set, six ML models including logistic regression (LR), support vector machine (SVM), random forest (RF), adaptive boosting (AdaBoost), extreme gradient boosting (XGBoost) and gradient boosting machine (GBM) were developed. These models were assessed by the area under curve (AUC) of receiver operating characteristic on the testing set. The related risk factors and outcomes of pneumonia were also probed based on the chosen model. RESULTS: 591 OLT patients were eventually included and 253 (42.81%) were diagnosed with postoperative pneumonia, which was associated with increased postoperative hospitalization and mortality (P < 0.05). Among the six ML models, XGBoost model performed best. The AUC of XGBoost model on the testing set was 0.734 (sensitivity: 52.6%; specificity: 77.5%). Pneumonia was notably associated with 14 items features: INR, HCT, PLT, ALB, ALT, FIB, WBC, PT, serum Na+, TBIL, anesthesia time, preoperative length of stay, total fluid transfusion and operation time. CONCLUSION: Our study firstly demonstrated that the XGBoost model with 14 common variables might predict postoperative pneumonia in OLT patients.

16.
Korean J Radiol ; 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33856135

RESUMEN

OBJECTIVE: We implemented a novel resectable myocardial model for mock myectomy using a hybrid method of three-dimensional (3D) printing and silicone molding for patients with apical hypertrophic cardiomyopathy (ApHCM). MATERIALS AND METHODS: From January 2019 through May 2020, 3D models from three patients with ApHCM were generated using the end-diastolic cardiac CT phase image. After computer-aided designing of measures to prevent structural deformation during silicone injection into molding, 3D printing was performed to reproduce anatomic details and molds for the left ventricular (LV) myocardial mass. We compared the myocardial thickness of each cardiac segment and the LV myocardial mass and cavity volumes between the myocardial model images and cardiac CT images. The surgeon performed mock surgery, and we compared the volume and weight of the resected silicone and myocardium. RESULTS: During the mock surgery, the surgeon could determine an ideal site for the incision and the optimal extent of myocardial resection. The mean differences in the measured myocardial thickness of the model (0.3, 1.0, 6.9, and 7.3 mm in the basal, midventricular, apical segments, and apex, respectively) and volume of the LV myocardial mass and chamber (36.9 mL and 14.8 mL, 2.9 mL and -9.4 mL, and 6.0 mL and -3.0 mL in basal, mid-ventricular and apical segments, respectively) were consistent with cardiac CT. The volume and weight of the resected silicone were similar to those of the resected myocardium (6 mL [6.2 g] of silicone and 5 mL [5.3 g] of the myocardium in patient 2; 12 mL [12.5 g] of silicone and 11.2 mL [11.8 g] of the myocardium in patient 3). CONCLUSION: Our 3D model created using hybrid 3D printing and silicone molding may be useful for determining the extent of surgery and planning surgery guided by a rehearsal platform for ApHCM.

17.
Pol J Microbiol ; 70(1): 3-11, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33815522

RESUMEN

Aspergillus fumigatus is one of the ubiquitous fungi with airborne conidia, which accounts for most aspergillosis cases. In immunocompetent hosts, the inhaled conidia are rapidly eliminated. However, immunocompromised or immunodeficient hosts are particularly vulnerable to most Aspergillus infections and invasive aspergillosis (IA), with mortality from 50% to 95%. Despite the improvement of antifungal drugs over the last few decades, the therapeutic effect for IA patients is still limited and does not provide significant survival benefits. The drawbacks of antifungal drugs such as side effects, antifungal drug resistance, and the high cost of antifungal drugs highlight the importance of finding novel therapeutic and preventive approaches to fight against IA. In this article, we systemically addressed the pathogenic mechanisms, defense mechanisms against A. fumigatus, the immune response, molecular aspects of host evasion, and vaccines' current development against aspergillosis, particularly those based on AFMP4 protein, which might be a promising antigen for the development of anti-A. fumigatus vaccines.

18.
Zhongguo Zhen Jiu ; 41(3): 288-92, 2021 Mar 12.
Artículo en Chino | MEDLINE | ID: mdl-33798312

RESUMEN

OBJECTIVE: To observe the efficacy of acupuncture combined with Heixiaoyao powder for children with cerebral palsy (liver-qi stagnation, spleen-kidney deficiency syndrome) and its effect on serum immune indexes and nerve growth related protein. METHODS: A total of 180 children with cerebral palsy were randomly divided into a combined group (60 cases, 2 cases dropped off), an acupuncture group (60 cases, 4 cases dropped off) and a Chinese medication group (60 cases, 5 cases dropped off). On the basis of conventional treatment, the children in the combined group were treated with acupuncture [Baihui (GV 20), Sishencong (EX-HN 1), Shenting (GV 24), Benshen (GB 13), 30 min each time, twice a day] and Heixiaoyao powder; the children in the acupuncture group were treated with acupuncture, and the children in the Chinese medication group were treated with Heixiaoyao powder, the treatment was same with the combined group. All the children were treated for 6 consecutive days and rest for 1 day, totaling for 8 weeks. The Gesell developmental schedules (GDS) and TCM symptom scores were recorded before treatment, after treatment and at 3-month, 6-month and 12-month follow-up visit; the serum immune indexes (IgA, IgG and IgM) and nerve growth related protein [myelin basic protein (MBP), high mobility group box-1 (HMGB1), neuronspecific enolase (NSE)] were detected before and after treatment. The clinical efficacy of each group was evaluated. RESULTS: The total effective rate was 91.4% (53/58) in the combined group, which was higher than 80.4% (45/56) in the acupuncture group and 78.2% (43/55) in the Chinese medication group (P<0.05). Compared before treatment, the GDS scores in the three groups were increased and the TCM symptom scores were reduced after treatment and at 3-month, 6-month and 12-month follow-up visit (P<0.05). The GDS score in the combined group was higher than that in the acupuncture group and the Chinese medication group, and the TCM symptom score was lower than that in the acupuncture group and Chinese medication group (P<0.05). After treatment, the serum levels of IgA, IgG and IgM in the combined group were increased (P<0.05), and the serum levels of MBP, HMGBl and NSE were decreased (P<0.05), and the improvements were superior to those in the acupuncture group and the Chinese medication group (P<0.05). CONCLUSION: Acupuncture combined with Heixiaoyao powder could effectively improve the development quotient in children with cerebral palsy (liver-qi stagnation, spleen-kidney deficiency syndrome), regulate the serum immune indexes and nerve growth related protein levels.


Asunto(s)
Terapia por Acupuntura , Parálisis Cerebral , Puntos de Acupuntura , Parálisis Cerebral/tratamiento farmacológico , Niño , Humanos , Polvos , Resultado del Tratamiento
19.
Eur J Med Chem ; 216: 113316, 2021 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-33676300

RESUMEN

A series of novel N-benzylbenzamide derivatives were designed and synthesized as tubulin polymerization inhibitors. Among fifty-one target compounds, compound 20b exhibited significant antiproliferative activities with IC50 values ranging from 12 to 27 nM against several cancer cell lines, and possessed good plasma stability and satisfactory physicochemical properties. Mechanism studies demonstrated that 20b bound to the colchicine binding site and displayed potent anti-vascular activity. Notably, the corresponding disodium phosphate 20b-P exhibited an excellent safety profile with the LD50 value of 599.7 mg/kg (i.v. injection), meanwhile, it significantly inhibited tumor growth and decreased microvessel density in liver cancer cell H22 allograft mouse model without obvious toxicity. Collectively, 20b and 20b-P are novel promising anti-tubulin agents with more druggable properties and deserve to be further investigated for cancer therapy.


Asunto(s)
Antineoplásicos/química , Benzamidas/química , Diseño de Fármacos , Moduladores de Tubulina/química , Tubulina (Proteína)/química , Animales , Antineoplásicos/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Benzamidas/metabolismo , Benzamidas/farmacología , Benzamidas/uso terapéutico , Sitios de Unión , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Colchicina/química , Colchicina/metabolismo , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Ratones , Ratones Endogámicos ICR , Simulación del Acoplamiento Molecular , Neoplasias/tratamiento farmacológico , Neovascularización Fisiológica/efectos de los fármacos , Relación Estructura-Actividad , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/metabolismo , Moduladores de Tubulina/farmacología , Moduladores de Tubulina/uso terapéutico
20.
Cancer Med ; 10(7): 2423-2441, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33666372

RESUMEN

BACKGROUND: Numerous reports on microRNAs have illustrated their role in tumor growth and metastasis. Recently, a new prognostic factor, miR-125b-2-3p, has been identified for predicting chemotherapeutic sensitivity in advanced colorectal cancer (CRC). However, the specific mechanisms and biological functions of miR-125b-2-3p in advanced CRC under chemotherapy have yet to be elucidated. METHODS: MiR-125b-2-3p expression was detected by real-time PCR (RT-PCR) in CRC tissues. The effects of miR-125b-2-3p on the growth, metastasis, and drug sensitivity of CRC cells were tested in vitro and in vivo. Based on multiple databases, the upstream competitive endogenous RNAs (ceRNAs) and the downstream genes for miR-125b-2-3p were predicted by bioinformatic analysis, followed by the experiments including luciferase reporter assays, western blot assays, and so on. RESULTS: MiR-125b-2-3p was significantly lowly expressed in the tissues and cell lines of CRC. Higher expression of miR-125b-2-3p was associated with relatively lower proliferation rates and fewer metastases. Moreover, overexpressed miR-125b-2-3p remarkably improved chemotherapeutic sensitivity of CRC in vivo and in vitro. Mechanistically, miR-125b-2-3p was absorbed by long noncoding RNA (lncRNA) XIST regulating WEE1 G2 checkpoint kinase (WEE1) expression. The upregulation of miR-125b-2-3p inhibited the proliferation and epithelial-mesenchymal transition (EMT) of CRC induced by lncRNA XIST. CONCLUSIONS: Lower miR-125b-2-3p expression resulted in lower sensitivity of CRC to chemotherapy and was correlated with poorer survival of CRC patients. LncRNA XIST promoted CRC metastasis acting as a ceRNA for miR-125b-2-3p to mediate WEE1 expression. LncRNA XIST-miR-125b-2-3p-WEE1 axis not only regulated CRC growth and metastasis but also contributed to chemotherapeutic resistance to CRC.

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