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•Concept of plant-based biofactories for therapeutics and biologics.•Industrial preference of transient expression system—agroinfiltration.•Advancement of virus-like particles from ...epitope presentation to nanomedicine.•Recent progress of plant-made therapeutics and biologics against human diseases.
Production of proteins in plants for human health applications has become an attractive strategy attributed by their potentials for low-cost production, increased safety due to the lack of human or animal pathogens, scalability and ability to produce complex proteins. A major milestone for plant-based protein production for use in human health was achieved when Protalix BioTherapeutics produced taliglucerase alfa (Elelyso®) in suspension cultures of a transgenic carrot cell line for the treatment of patients with Gaucher's disease, was approved by the USA Food and Drug Administration in 2012. In this review, we are highlighting various approaches for plant-based production of proteins and recent progress in the development of plant-made therapeutics and biologics for the prevention and treatment of human diseases.
A study combining high resolution mass spectrometry (liquid chromatography-quadrupole time-of-flight-mass spectrometry, UPLC-QTof-MS) and chemometrics for the analysis of post-mortem brain tissue ...from subjects with Alzheimer’s disease (AD) (n = 15) and healthy age-matched controls (n = 15) was undertaken. The huge potential of this metabolomics approach for distinguishing AD cases is underlined by the correct prediction of disease status in 94–97% of cases. Predictive power was confirmed in a blind test set of 60 samples, reaching 100% diagnostic accuracy. The approach also indicated compounds significantly altered in concentration following the onset of human AD. Using orthogonal partial least-squares discriminant analysis (OPLS-DA), a multivariate model was created for both modes of acquisition explaining the maximum amount of variation between sample groups (Positive Mode-R2 = 97%; Q2 = 93%; root mean squared error of validation (RMSEV) = 13%; Negative Mode-R2 = 99%; Q2 = 92%; RMSEV = 15%). In brain extracts, 1264 and 1457 ions of interest were detected for the different modes of acquisition (positive and negative, respectively). Incorporation of gender into the model increased predictive accuracy and decreased RMSEV values. High resolution UPLC-QTof-MS has not previously been employed to biochemically profile post-mortem brain tissue, and the novel methods described and validated herein prove its potential for making new discoveries related to the etiology, pathophysiology, and treatment of degenerative brain disorders.
Glucagon‐like peptide‐1 (GLP‐1) is an incretin hormone secreted by the small intestine in response to nutrient ingestion. It has wide‐ranging effects on glucose metabolism, including stimulation of ...insulin release, inhibition of glucagon secretion, reduction of gastric emptying and augmentation of satiety. Importantly, the insulinotropic actions of GLP‐1 are uniquely dependent on ambient glucose concentrations, and it is this particular characteristic which has led to its recent emergence as a treatment for type 2 diabetes. Although the major physiological function of GLP‐1 appears to be in relation to glycaemic control, there is growing evidence to suggest that it may also play an important role in the cardiovascular system. GLP‐1 receptors (GLP‐1Rs) are expressed in the heart and vasculature of both rodents and humans, and recent studies have demonstrated that GLP‐1R agonists have wide‐ranging cardiovascular actions, such as modulation of heart rate, blood pressure, vascular tone and myocardial contractility. Importantly, it appears that these agents may also have beneficial effects in the setting of cardiovascular disease (CVD). For example, GLP‐1 has been found to exert cardioprotective actions in experimental models of dilated cardiomyopathy, hypertensive heart failure and myocardial infarction (MI). Preliminary clinical studies also indicate that GLP‐1 infusion may improve cardiac contractile function in chronic heart failure patients with and without diabetes, and in MI patients after successful angioplasty. This review will discuss the current understanding of GLP‐1 biology, examine its emerging cardiovascular actions in both health and disease and explore the potential use of GLP‐1 as a novel treatment for CVD.
Automated recognition of mouse behaviors is crucial in studying psychiatric and neurologic diseases. To achieve this objective, it is very important to analyze the temporal dynamics of mouse ...behaviors. In particular, the change between mouse neighboring actions is swift in a short period. In this paper, we develop and implement a novel hidden Markov model (HMM) algorithm to describe the temporal characteristics of mouse behaviors. In particular, we here propose a hybrid deep learning architecture, where the first unsupervised layer relies on an advanced spatial-temporal segment Fisher vector encoding both visual and contextual features. Subsequent supervised layers based on our segment aggregate network are trained to estimate the state-dependent observation probabilities of the HMM. The proposed architecture shows the ability to discriminate between visually similar behaviors and results in high recognition rates with the strength of processing imbalanced mouse behavior datasets. Finally, we evaluate our approach using JHuang's and our own datasets, and the results show that our method outperforms other state-of-the-art approaches.
Sprouting is a traditional processing method which has been used for centuries to improve the nutritional value of cereals and legumes. There has been growing interest in sprouted products in recent ...years due to a high demand for more natural and healthy foods. Phytate is the primary storage form of phosphorus in plants. It is long recognised to affect human health as it forms insoluble complexes with minerals such as iron and zinc in cereals and legumes, thereby preventing their absorption in the body. Sprouting activates the enzyme phytase, which degrades phytate, thereby improving mineral bioaccessibility and bioavailability. The extent of phytate reduction varies depending on the sprouting conditions, cereal/legume species, cultivar and native phytase activity. Sprouting has been associated with increased iron, zinc and calcium bioaccessibility in many studies, but this appears to differ in cereals and legumes, which possibly is due to the presence of other ‘antinutrients’. Protein digestibility also appears to be positively correlated with phytate reduction albeit less than for minerals. It is not possible to accurately predict the influence of sprouting on nutrient bioavailability because so few studies have been conducted. Further research is required to determine whether the commercial production of sprouted cereals and legumes can increase the nutritional value and health benefits of commercial end products.
•Nuclear submarines could be effective refuges from several types of global catastrophes.•Existing military submarines could be upgraded for this function with relatively low cost.•Contemporary ...submarines could provide several months of surface independence.•A specially designed fleet of nuclear submarines could potentially survive years or even decades under water.
Recently many methods for reducing the risk of human extinction have been suggested, including building refuges underground and in space. Here we will discuss the perspective of using military nuclear submarines or their derivatives to ensure the survival of a small portion of humanity who will be able to rebuild human civilization after a large catastrophe. We will show that it is a very cost-effective way to build refuges, and viable solutions exist for various budgets and timeframes. Nuclear submarines are surface independent, and could provide energy, oxygen, fresh water and perhaps even food for their inhabitants for years. They are able to withstand close nuclear explosions and radiation. They are able to maintain isolation from biological attacks and most known weapons. They already exist and need only small adaptation to be used as refuges. But building refuges is only “Plan B” of existential risk preparation; it is better to eliminate such risks than try to survive them.
Over 2000 years the Catholic Church has slowly developed a posture towards technology which is predominantly techno-optimist and techno-progressive, and yet the Church does not have this reputation ...today. Concomitantly, Church institutions and individuals have made crucial contributions to the advance of science and technology, yet despite this practical effort to better human development, Christian theology has been remarkably uninterested in the subject of technology. This lack of interest is no longer tenable; scholars of religion and theologians should seriously engage technology because it is empowering humanity in ways that were previously reserved only for gods. This blind spot has not only hampered the Church’s ability to understand itself and our world, but also impeded the ability of the Church to fulfill its mission. Pope Francis’s 2015 encyclical Laudato Si has begun to address this neglect, but is best understood in the context of Christian history, not only as written, but more so as practiced.
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•Volatilome evolution of sonicated wholegrain brown rice (WBR) was assessed.•WBR starch digestibility affected by high-power ultrasound (HPU) was characterized.•HPU-associated markers ...of WBR included aldehydes, acids, esters and 2-pentyl-furan.•HPU pretreatments significantly inhibited the lipid oxidation during WBR storage.•Untargeted and targeted methods supported the use of HPU processing of WBR grains.
The potential of high-power ultrasonication (HPU) to enhance the physicochemical stability of bran-containing cereal products has been demonstrated, but the information concerning how the wholegrain volatilome and key quality-related chemical reactions evolve responding to HPU remains scarcely reported. The objective of this work was to examine the headspace volatile fingerprinting features of sonicated wholegrain brown rice (WBR; 400 W, 28 kHz, 30 min) following an accelerated storage testing (37 °C, 20 days), and simultaneously to identify the key chemical reactions induced by ultrasonication. A total of 70 aroma compounds were identified by the untargeted headspace GC–MS, including 9 alkanes, 6 alkenes, 15 aldehydes, 6 furans, 12 ketones, 9 alcohols and 13 miscellaneous compounds. Multivariate statistical analysis demonstrated that HPU pretreatments before a storage process significantly influenced the volatilome evolution, as revealed by a clear classification between sonicated and unsonicated grains. Supervised orthogonal partial least squares discriminant analysis identified the volatiles including acetic acid, pentanoic acid, hexanal, ethyl hexanoate and 2-pentyl-furan as HPU-related markers, inferring that HPU mainly modified the chemical reactions involving lipid decomposition, free fatty acids oxidation and esterification. This was further confirmed by targeted monitoring of lipid peroxidation products, with 13.22–14.84 % of MDA contents reduced (p < 0.05) in sonicated samples after storage. Besides, the ultrasonic effects resulted in a slight improvement of in vitro starch digestibility of WBR samples depending on the rice ecotype. This investigation demonstrated the potential of HPU pretreatments for prolonging the oxidative stability of WBR grains, without significantly compromising digestion properties.
The two plants investigated here (Fagonia cretica L. and Hedera nepalensis K. Koch) have been previously reported as natural folk medicines for the treatment of diabetes but until now no scientific ...investigation of potential anti-diabetic effects has been reported.
In vitro inhibitory effect of the two tested plants and their five isolated compounds on the dipeptidyl peptidase 4 (DPP-4) was studied for the assessment of anti-diabetic activity.
A crude extract of Fagonia cretica possessed good inhibitory activity (IC50 value: 38.1μg/ml) which was also present in its n-hexane (FCN), ethyl acetate (FCE) or aqueous (FCA) fractions. A crude extract of Hedera nepalensis (HNC) possessed even higher inhibitory activity (IC50 value: 17.2μg/ml) and this activity was largely retained when further fractionated in either ethyl acetate (HNE; IC50: 34.4μg/ml) or n-hexane (HNN; 34.2μg/ml). Bioactivity guided isolation led to the identification of four known compounds (isolated for the first time) from Fagonia cretica: quinovic acid (1), quinovic acid-3β-O-β-d-glycopyranoside (2), quinovic acid-3β-O-β-d-glucopyranosyl-(28→1)-β-d-glucopyranosyl ester (3), and stigmasterol (4) all of which inhibited DPP-4 activity (IC50: 30.7, 57.9, 23.5 and >100µM, respectively). The fifth DPP-4 inhibitor, the triterpenoid lupeol (5) was identified in Hedera nepalensis (IC50: 31.6μM).
The experimental study revealed that Fagonia cretica and Hedera nepalensis contain compounds with significant DPP-4 inhibitory activity which should be further investigated for their anti-diabetic potential.
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OBJECTIVE:To investigate the effectiveness of a neck strengthening program on the isometric neck strength profile of male rugby union players.
DESIGN:Controlled laboratory study.
SETTING:Professional ...rugby union club.
PARTICIPANTS:Fifteen professional and 10 semiprofessional rugby union players.
INTERVENTIONS:The 15 professional players undertook a 5-week neck strengthening intervention, which was performed twice per week, whereas the 10 semiprofessional players acted as the control group.
MAIN OUTCOME MEASURES:Isometric strength of the neck musculature was tested using a hand-held dynamometer, for flexion (F), extension (E), left-side flexion (LSF), and right-side flexion (RSF). Preintervention and postintervention evaluations were undertaken.
RESULTS:No significant between-group differences in isometric neck strength were noted preintervention. A significant main effect for time was observed (P < 0.05), whereby the intervention group increased isometric neck strength in all planes after the 5-week intervention (F preintervention = 334.45 ± 39.31 N vs F postintervention 396.05 ± 75.55 N; E preintervention = 606.19 ± 97.34 vs E postintervention = 733.88 ± 127.16 N; LSF preintervention = 555.56 ± 88.34 N vs LSF postintervention = 657.14 ± 122.99 N; RSF preintervention = 570.00 ± 106.53 N vs RSF postintervention = 668.00 ± 142.18 N). No significant improvement in neck strength was observed for control group participants.
CONCLUSIONS:The results of the present study indicate that a 5-week neck strengthening program improves isometric neck strength in rugby union players, which may have implications for injury prevention, screening, and rehabilitation.
CLINICAL RELEVANCE:The strengthening program described in the present study may facilitate rehabilitation specialists in the development of neck injury prevention, screening, and rehabilitation protocols.