AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs. two doses. To further enhance immunogenicity, AKS-452 was evaluated in formulations containing a panel of adjuvants in which the water-in-oil adjuvant, Montanide™ ISA 720, enhanced neutralizing IgG titers by approximately 7-fold after one and two doses in mice, including the neutralization of live SARS-CoV-2 virus infection of VERO-E6 cells. Furthermore, ISA 720-adjuvanted AKS-452 was immunogenic in rabbits and non-human primates (NHPs) and protected from infection and clinical symptoms with live SARS-CoV-2 virus in NHPs (USA-WA1/2020 viral strain) and the K18 human ACE2-trangenic (K18-huACE2-Tg) mouse (South African B.1.351 viral variant). These preclinical studies support the initiation of Phase I clinical studies with adjuvanted AKS-452 with the expectation that this room-temperature stable, Fc-fusion subunit vaccine can be rapidly and inexpensively manufactured to provide billions of doses per year especially in regions where the cold-chain is difficult to maintain. 相似文献
BackgroundIschemia reperfusion (I/R) play an imperative role in the expansion of cardiovascular disease. Sinomenine (SM) has been exhibited to possess antioxidant, anticancer, anti-inflammatory, antiviral and anticarcinogenic properties. The aim of the study was scrutinized the cardioprotective effect of SM against I/R injury in rat.MethodsRat were randomly divided into normal control (NC), I/R control and I/R + SM (5, 10 and 20 mg/kg), respectively. Ventricular arrhythmias, body weight and heart weight were estimated. Antioxidant, inflammatory cytokines, inflammatory mediators and plasmin system indicator were accessed.ResultsPre-treated SM group rats exhibited the reduction in the duration and incidence of ventricular fibrillation, ventricular ectopic beat (VEB) and ventricular tachycardia along with suppression of arrhythmia score during the ischemia (30 and 120 min). SM treated rats significantly (P < 0.001) altered the level of antioxidant parameters. SM treatment significantly (P < 0.001) repressed the level of creatine kinase MB (CK-MB), creatine kinase (CK) and troponin I (Tnl). SM treated rats significantly (P < 0.001) repressed the tissue factor (TF), thromboxane B2 (TXB2), plasminogen activator inhibitor 1 (PAI-1) and plasma fibrinogen (Fbg) and inflammatory cytokines and inflammatory mediators.ConclusionOur result clearly indicated that SM plays anti-arrhythmia effect in I/R injury in the rats via alteration of oxidative stress and inflammatory reaction. 相似文献
Objective: This study evaluated the physicochemical properties, fatty acid (FA) and phytochemical compositions, and free radical–scavenging potentials of oils from the bagasses: Costus afer stem (CA) and Saccharum officinarum stem (SB); agricultural residues; corn cobs (CC); tigernut chaff (TB); peanut hulls (GH); medicinal plants: Sphenocentrum jollyanum leaves (SJ) and Senna alata leaves (CS); and fodders: Pennisetum purpureum (PP), Panicum maximum (PM), and Chloris gayana stalks (CG).
Method: Oils from the samples were extracted using a mixture of n-hexane and isopropyl alcohol (3:2). The oils were analyzed for physicochemical properties using standard procedures, phytochemicals and FAs contents using gas chromatography-fluorescent ionization detection, and free radical–scavenging potentials using spectrophotometric methods of determination.
Results: The bagasse and residue oils contained lower moisture contents (1.13%–2.38%) and acid values (1.89–9.20?mg/KOH/g), while the GH oil produced the least refractive indices, saponification value, and oil yield. CA oil contained 78% saturated FA, while SB oils contained 73.65% saturated FA and an abundance of lignoceric, palmitoleic, oleic, and arachidic acid. CC oil contained mostly behenic acid (19.65%), and GH oil produced 87.04% saturated FA, while TB oil produced 56% unsaturated FA. Oils from SJ, CS, PP, PM, and CG contained between 48.34% and 57.09% unsaturated FA. The phytochemical composition showed that ribalinidine and sapogenin were most abundant in PM oil, while lunamarine, kaempferol, and catechin were most abundant in SJ oil. GH oil produced the highest amounts of phytate (53.81?µg/ml) and oxalate (39.47?µg/ml). TB oil and oils from SJ and CS, especially at higher concentrations, matched the scavenging potentials of the standards used.
Conclusions: Due to the thermal stability and amount of short chain fatty acids (SFAs) of the SB, CA, CC, and GH oils, they are more suitable for non-food industrial purposes, while TB, SJ, and CS oil properties are recommendable for therapeutic purposes, especially for relief of oxidative stress. 相似文献
Purpose: Beyond promising experimental results of sensory passive stimulations in spatial cognition disorders, some questions still remain regarding interests of these stimulations during the daily activities in neglect. The aim of this case-study was to evaluate the effects of a protocol combining left neck-muscle vibration with daily simple movements, like arm pointing movements, on perceptivo-locomotor deficits in a left spatial neglect patient.
Materials and methods: Two neuropsychological tests, one subjective straight-ahead pointing (SSA) test and one wheelchair navigation test were carried out before the combination protocol, immediately after, 1?h later, and 24?h later.
Results: The results showed a reduction of neglect spatial bias following the protocol lasted at least 24?h in all the tests (except for the SSA test due to the unavailability of the pointing device).
Conclusions: The range of improvements in the symptoms of spatial neglect suggests that this therapeutic intervention based on the combining neck-muscle vibration to voluntary arm movements could be a useful treatment for this condition. One of future investigation axes should be the development of a vibratory tool in order to facilitate the combining this proprioceptive stimulation to daily activities.
Implications for rehabilitation
Spatial neglect is a perplexing neuropsychological syndrome, affecting different domains of spatial cognition and impacting also the functional domain.
The treatments based on neck-muscle vibration are simple to use, non-invasive and requires none active participation of patient.
A therapeutic intervention based on the combining left neck-muscle vibration and voluntary arm movements in a left-spatial-neglect show a lasting reduction of symptoms especially in daily activities.
The combination of treatments based on the Bottom–Up approach opens innovative perspectives in rehabilitation.
ObjectiveTo compare corticospinal excitability and transcallosal inhibition between contralesional primary motor cortex (M1) and ipsilesional M1. We also investigated the correlation between transcallosal inhibition and upper extremity motor behavior.Materials and methods19 individuals with unilateral ischemic subacute stroke who had severe upper extremity impairment participated in this study. Corticospinal excitability was assessed by measuring the resting motor threshold, active motor threshold and motor evoked potential amplitude. Transcallosal inhibition was investigated by measuring the duration and depth of the ipsilateral silent period (ISP). The data from the two hemispheres were compared and the relationships of transcallosal inhibition with upper extremity motor impairment, grip strength and pinch strength were analyzed.ResultsResting motor threshold (p = 0.001) and active motor threshold (p = 0.001) were lower and motor evoked potential amplitude was higher (p = 0.001) in the contralesional M1 compared to the ipsilesional M1. However, there were no differences between the two M1s in ISP duration (p = 0.297) or ISP depth (p =0. 229). Transcallosal inhibition from the contralesional M1 was positively associated with motor impairment (ISP duration, p = 0.003; ISP depth, p = 0.017) and grip strength (ISP duration, p = 0.016; ISP depth, p = 0.045).ConclusionsSymmetric transcallosal inhibition between hemispheres and positive association of transcallosal inhibition from contralesional M1 with upper extremity motor behavior indicate that recruitment of contralesional M1 may be necessary for recovery in patients with severe upper extremity impairment after subacute ischemic stroke. 相似文献
Mechanical peak power output (PPO) is a determinant of performance in sprint cycling. The purpose of this study was to examine the relationship between PPO and putative physiological determinants of PPO in elite cyclists, and to compare sprint performance between elite sprint and endurance cyclists. Thirty-five elite cyclists (18 endurance; 17 sprint) performed duplicate sprint cycling laboratory tests to establish PPO and its mechanical components. Quadriceps femoris (QVOL) and hamstring muscle volume (HAMVOL) were assessed with MRI, vastus lateralis pennation angle (PθVL) and fascicle length (FLVL) were determined with ultrasound imaging, and neuromuscular activation of three muscles was assessed using EMG at PPO during sprint cycling. For the whole cohort, there was a wide variability in PPO (range 775-2025 W) with very large, positive, bivariate relationships between PPO and QVOL (r = .87), HAMVOL (r = .71), and PθVL (r = .81). Step-wise multiple regression analysis revealed that 87% of the variability in PPO between cyclists was explained by two variables QVOL (76%) and PθVL (11%). The sprint cyclists had greater PPO (+61%; P < .001 vs endurance), larger QVOL (P < .001), and BFVOL (P < .001) as well as more pennate vastus lateralis muscles (P < .001). These findings emphasize the importance of quadriceps muscle morphology for sprint cycling events. 相似文献
PurposeTo investigate dynamic variables obtained from retrospective computed tomography angiography for ability to predict thoracic endovascular aortic repair (TEVAR) outcomes in patients with complicated type B aortic dissection (cTBAD).Materials and MethodsSeventy-nine patients with cTBAD who received TEVAR from March 2009 to June 2018 were retrospectively enrolled. Relative true lumen area (r-TLA) was computed at the level of tracheal bifurcation every 5% of all R-R intervals. Parameters that reflect the state of intimal motion were evaluated, including difference between maximum and minimum r-TLA (D-TLA) and true lumen collapse. The endpoints comprised early (≤ 30 days) and late (> 30 days) outcomes after intervention.ResultsOverall early mortality rate was 13.9% (11/79), and early adverse events rate was 24.1% (19/79). Patients who received TEVAR within 2 days of symptom onset demonstrated the worst outcomes. A longer time of r-TLA < 25% in 1 cardiac cycle (P = .049) and larger D-TLA (P < .001) were correlated to an increased early death. In addition, D-TLA was an independent predictor of early mortality. Area under the curve of D-TLA was 0.849 (95% confidence interval 0.730–0.967) for predicting early mortality and 0.742 (95% CI 0.611–0.873) for predicting early adverse events. Survival and event-free survival rates during follow-up were decreased in the D-TLA > 21.5% group compared with the D-TLA ≤ 21.5% group (all P < .001).ConclusionsLarger D-TLA is correlated with worse postoperative outcomes and might be a crucial parameter for future risk stratification in patients with cTBAD. 相似文献