Search

Several evidences suggest that immuno-inflammatory responses are involved in the pathogenesis of anorexia nervosa (AN). Herein we investigate the possible alteration of key mediators of inflammation, redox balance, and neuroplasticity in the brain of rats showing an anorexic-like phenotype. We modeled AN in adolescent female rats using the activity-based anorexia (ABA) paradigm and measured gene expression levels of targets of interest in the prefrontal cortex (PFC) and dorsal hippocampus (DH). We observed reduced mRNA levels of pro-inflammatory cytokines IL-1β and TNF-α, the inflammasome NLRP3, and the microglial marker CD11b in both PFC and DH of ABA animals. Conversely, the mRNA of IL-6, which acts as both a pro-inflammatory and anti-inflammatory cytokine, was increased. Moreover, we observed an overall upregulation of different antioxidant enzymes in PFC, while their profile was not affected or opposite in the DH, with the exception of MT1α. Interestingly, ABA animals showed elevated levels of the neuroplasticity marker BDNF in both PFC and DH. Our data indicate that ABA induction is associated with anatomical-specific cerebral alteration of mediators of neuroinflammation, oxidative balance and neuroplasticity. Although more research should be conducted, these results add important information about the role of these systems in the complex AN etiopathogenesis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Quantum machine learning is often highlighted as one of the most promising practical applications for which quantum computers could provide a computational advantage. However, a major obstacle to the widespread use of quantum machine learning models in practice is that these models, even once trained, still require access to a quantum computer in order to be evaluated on new data. To solve this issue, we introduce a class of quantum models where quantum resources are only required during training, while the deployment of the trained model is classical. Specifically, the training phase of our models ends with the generation of a 'shadow model' from which the classical deployment becomes possible. We prove that: (i) this class of models is universal for classically-deployed quantum machine learning; (ii) it does have restricted learning capacities compared to 'fully quantum' models, but nonetheless (iii) it achieves a provable learning advantage over fully classical learners, contingent on widely believed assumptions in complexity theory. These results provide compelling evidence that quantum machine learning can confer learning advantages across a substantially broader range of scenarios, where quantum computers are exclusively employed during the training phase. By enabling classical deployment, our approach facilitates the implementation of quantum machine learning models in various practical contexts., (© 2024. The Author(s).)

The development of media for cell culture is a major issue in the biopharmaceutical industry, for the production of therapeutics, immune-modulating molecules and protein antigens. Chemically defined media offer several advantages, as they are free of animal-derived components and guarantee high purity and a consistency in their composition. Microorganisms of the genus Leishmania represent a promising cellular platform for production of recombinant proteins, but their maintenance requires supplements of animal origin, such as hemin and fetal bovine serum. In the present study, three chemically defined media were assayed for culturing Leishmania tarentolae, using both a wild-type strain and a strain engineered to produce a viral antigen. Among the three media, Schneider's Drosophila Medium supplemented with Horseradish Peroxidase proved to be effective for the maintenance of L. tarentolae promastigotes, also allowing the heterologous protein production by the engineered strain. Finally, the engineered strain was maintained in culture up to the 12th week without antibiotic, revealing its capability to produce the recombinant protein in the absence of selective pressure., (© 2024. The Author(s).)

Scientific and industrial reasons dictate the study of the solid state of imepitoin, a highly safe and tolerable anticonvulsant drug used in the therapy of epileptic dogs that was approved in the Europe Union in 2013. Our investigations allowed us to discover the existence of a new polymorph of imepitoin, which finds itself in a monotropic relationship with the crystalline form (polymorph I) already known and present on the market. This form (polymorph II), obtained by crystallization from xylene, remains metastable under ambient conditions for at least 1 year. Both solid forms were characterized by thermal (DSC and TGA), spectroscopic (FT-IR and Raman), microscopic (SEM and HSM), and diffractometric techniques. The thermodynamic relationship between the two polymorphs (monotropic) is such that it is not possible to study the melting of polymorph II, not even by adopting appropriate experimental strategies. Our measurements highlighted that the melting peak of imepitoin actually also includes an onset of melt decomposition. The ab initio structure solution, obtained from synchrotron X-ray powder diffraction data collected at room temperature, allowed us to determine the crystal structure of the new polymorph (II). It crystallizes in the monoclinic crystal structure, P2 1 / c space group (#14), with a = 14.8687(6) Å, b = 7.2434(2) Å, c = 12.5592(4) Å, β = 107.5586(8)°, V = 1289.61(8) Å3, and Z = 4.

The development of new antipsychotics with pro-cognitive properties and less side effects represents a priority in schizophrenia drug research. In this study, we present for the first time a preclinical exploration of the effects of the promising natural atypical antipsychotic Methyl-2-Amino-3- Methoxybenzoate (MAM), a brain-penetrable protoalkaloid from the seed of the plant Nigella damascena. Using animal models related to hyperdopaminergic activity, namely the pharmacogenetic apomorphine (D2/D1 receptor agonist)-susceptible (APO-SUS) rat model and pharmacologically induced mouse and rat models of schizophrenia, we found that MAM reduced gnawing stereotypy and climbing behaviours induced by dopaminergic agents. This predicts antipsychotic activity. In line, MAM antagonized apomorphine-induced c-Fos and NPAS4 mRNA levels in post-mortem brain nucleus accumbens and dorsolateral striatum of APO-SUS rats. Furthermore, phencyclidine (PCP, an NMDA receptor antagonist) and 2,5-Dimethoxy-4-iodoamphetamine (DOI, a 5HT2A/2C receptor agonist) induced prepulse inhibition deficits, reflecting the positive symptoms of schizophrenia, which were rescued by treatment with MAM and atypical antipsychotics alike. Post-mortem brain immunostaining revealed that MAM blocked the strong activation of both PCP- and DOI-induced c-Fos immunoreactivity in a number of cortical areas. Finally, during a 28-day subchronic treatment regime, MAM did not induce weight gain, hyperglycemia, hyperlipidemia or hepato- and nephrotoxic effects, side effects known to be induced by atypical antipsychotics. MAM also did not show any cataleptic effects. In conclusion, its brain penetrability, the apparent absence of preclinical side effects, and its ability to antagonize positive and cognitive symptoms associated with schizophrenia make MAM an exciting new antipsychotic drug that deserves clinical testing., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)