Obesity wars: hypothalamic sEVs a new hope

There are currently several pharmacological therapies available for the treatment of obesity, targeting both the central nervous system (CNS) and peripheral tissues. In recent years, small extracellular vesicles (sEVs) have been shown to be involved in many pathophysiological conditions. Because of their special nanosized structure and contents, sEVs can activate receptors and trigger intracellular pathways in recipient cells. Notably, in addition to transferring molecules between cells, sEVs can also alter their phenotypic characteristics. The purpose of this review is to discuss how sEVs can be used as a CNS-targeted strategy for treating obesity. Furthermore, we will evaluate current findings, such as the sEV-mediated targeting of hypothalamic AMP-activated protein kinase (AMPK), and discuss how they can be translated into clinical application.publishedVersio

Understanding the Effects of Antipsychotics on Appetite Control

Antipsychotic drugs (APDs) represent a cornerstone in the treatment of schizophrenia and other psychoses. The effectiveness of the first generation (typical) APDs are hampered by so-called extrapyramidal side effects, and they have gradually been replaced by second (atypical) and third-generation APDs, with less extrapyramidal side effects and, in some cases, improved efficacy. However, the use of many of the current APDs has been limited due to their propensity to stimulate appetite, weight gain, and increased risk for developing type 2 diabetes and cardiovascular disease in this patient group. The mechanisms behind the appetite-stimulating effects of the various APDs are not fully elucidated, partly because their diverse receptor binding profiles may affect different downstream pathways. It is critical to identify the molecular mechanisms underlying drug-induced hyperphagia, both because this may lead to the development of new APDs, with lower appetite-stimulating effects but also because such insight may provide new knowledge about appetite regulation in general. Hence, in this review, we discuss the receptor binding profile of various APDs in relation to the potential mechanisms by which they affect appetite.publishedVersio

Production and identification of intricate bioactive oligosaccharides from Nyctanthesarbor-tristis leaves by a combination of enzymatic, HPAEC and MALDI-TOF-MS techniques

1471-1477Non-digestible oligosaccharides are associated with positive health outcomes; however, hemicellulosic oligosaccharides of N. arbor-tristis have not been studied. Herein, we report production of hemicellulosic oligosaccharides from its leaves and their identification. A series of complex neutral oligosaccharides (1-16), produced by endo-(1,4)--D-glucanase digestion of the alkali extracted xyloglucan, have been identified by chemical, HPAE chromatographic and MALDI-mass spectrometric techniques. Additionally, xylan enriched hemicellulose-A fraction upon endo-(1,4)--D-xylanase digestion yield several acidic and neutral xylo-oligosaccharides (17-24), each containing a backbone of -(1,4)-D-Xylp units substituted at position 2 with a single stub of D-Xylp or 4-O-Me-D-GlcpA residues. The structural diversity and high water solubility of these enzyme-generated oligosaccharides suggested promising health implications

Production and identification of intricate bioactive oligosaccharides from Nyctanthesarbor-tristis leaves by a combination of enzymatic, HPAEC and MALDI-TOF-MS techniques

Nondigestible oligosaccharides are associated with positive health outcomes; however, hemicellulosic oligosaccharides of N. arbor-tristis have not been studied. Herein we report production hemicellulosic oligosaccharides from its leaves and their identification. A series of complex neutral oligosaccharides (1-16), produced by endo-(1,4)-b-d-cellulase digestion of the alkali extracted xyloglucan, were identified by chemical, HPAE chromatographic and MALDI mass spectrometric techniques. Additionally, xylan enriched hemicellulose-A fraction upon endo-(1,4)-b-d-xylanase digestion yielded several acidic and neutral xylo-oligosaccharides (17-24), each containing a backbone of b-(1,4)-d-Xylp units substituted at position 2 with a single stub of d-Xylp and 4-O-Me-d-GlcpA residues. The structural diversity and high-water solubility of these enzyme-generated oligosaccharides implied promising health implication

Efficient Threshold FHE with Application to Real-Time Systems

Threshold Fully Homomorphic Encryption (ThFHE) enables arbitrary computation over encrypted data while keeping the decryption key distributed across multiple parties at all times. ThFHE is a key enabler for threshold cryptography and, more generally, secure distributed computing. Existing ThFHE schemes inherently require highly inefficient parameters and are unsuitable for practical deployment. In this paper, we take the first step towards making ThFHE practically usable by (i) proposing a novel ThFHE scheme with a new analysis resulting in significantly improved parameters; (ii) and providing the first practical ThFHE implementation benchmark based on Torus FHE. • We propose the first practical ThFHE scheme with a polynomial modulus-to-noise ratio that supports practically efficient parameters while retaining provable security based on standard quantum-safe assumptions. We achieve this via a novel Rényi divergence-based security analysis of our proposed threshold decryption mechanism. • We present an optimized software implementation of a Torus-FHE based instantiation of our proposed ThFHE scheme that builds upon the existing Torus FHE library and supports (distributed) decryption on highly resource-constrained ARM-based handheld devices. Along the way, we implement several extensions to the Torus FHE library, including a Torus-based linear integer secret sharing subroutine to support ThFHE key sharing and distributed decryption for any threshold access structure. We illustrate the efficacy of our proposal via an end-to-end use case involving encrypted computations over a real medical database, and distributed decryptions of the computed result on resource-constrained ARM-based handheld devices

Neuroimmune Interactions in Fetal Alcohol Spectrum Disorders: Potential Therapeutic Targets and Intervention Strategies

Fetal alcohol spectrum disorders (FASD) are a set of abnormalities caused by prenatal exposure to ethanol and are characterized by developmental defects in the brain that lead to various overt and non-overt physiological abnormalities. Growing evidence suggests that in utero alcohol exposure induces functional and structural abnormalities in gliogenesis and neuron–glia interactions, suggesting a possible role of glial cell pathologies in the development of FASD. However, the molecular mechanisms of neuron–glia interactions that lead to the development of FASD are not clearly understood. In this review, we discuss glial cell pathologies with a particular emphasis on microglia, primary resident immune cells in the brain. Additionally, we examine the involvement of several neuroimmune molecules released by glial cells, their signaling pathways, and epigenetic mechanisms responsible for FASD-related alteration in brain functions. Growing evidence suggests that extracellular vesicles (EVs) play a crucial role in the communication between cells via transporting bioactive cargo from one cell to the other. This review emphasizes the role of EVs in the context of neuron–glia interactions during prenatal alcohol exposure. Finally, some potential applications involving nutritional, pharmacological, cell-based, and exosome-based therapies in the treatment of FASD are discussed

Biochemical assessment of extract from <em>Oxalis corniculata</em> L.: Its role in food preservation, antimicrobial and antioxidative paradigms using <em>in situ</em> and <em>in vitro</em> models

230-243Food poisoning, often due to microbial contamination and improper storage practice, is a matter of concern. Plants and plant based products are gaining interest in processed food in food industry as an alternative to synthetic antimicrobials. In this context, here, we analysed flavonoid rich methanolic extract from the creeping woodsorrel, Oxalis corniculata L. leaf for its biochemical assessments along with its bioactivity against some common pathogenic bacteria. The bioactivity of the extract as evaluated in both in vitro and in situ methods, verified that the Oxalis corniculata leafextract exert reduces power, hydroxyl radical scavenging activity, inhibition in liposome peroxidation, and DPPH free radical quenching activity. The extract also inhibited the formation of peroxide during subsequent storage in the oil-emulsion system as well as in heated oil. The greater reducing activity of the extract prevented hydroxyl radical induced pUC18 DNA strand breaks and there by retain its original conformation. The extract also prevented the oxidative damage of goat liver cells during Fenton reaction. In vitro antimicrobial experiments implied that extract has inhibitory effect against Staphylococcus aureus, Escherichia coli, Salmonella Typhi, S. Typhiimurium and Vibrio cholera. E. coli showed the highest and V. cholera the lowest sensitivities against the extract. Moreover, the extract can be utilized for preservation of fish meat as it prevented the growth of food poisoning bacteria S. aureus during storage at 10°C. HPLC chromatogram detected the predominance of three active principal components, i.e. flavonoids in the following order: rutin>p-hydroxybenzoic acid>ferulic acid