The acute effects of methoxphenidine on behaviour and pharmacokinetics profile in animal model.

Methoxphenidine (MXP) is classified as a new psychoactive substance that has recently emerged on the illicit drug market. Understanding the pharmacological and behavioural profiles of newly emerging drugs is essential for a better understanding of their psychotropic effects and potential toxicity. Therefore, in this study, we investigated a broad range of effects of acute MXP administration: pharmacokinetics in the brain and serum; behaviour (open field and prepulse inhibition), systemic toxicity (lethal dose; LD 50), and histopathology changes in parenchymal organs of Wistar rats.

Retinal pharmacodynamic and pharmacokinetic profile of cannabidiol in an in vivo model of retinal excitotoxicity.

Cannabidiol (CBD) is one of the principal constituents of Cannabis Sativa with no psychoactive properties. CBD is a promising neuroprotective compound bearing anti-inflammatory and antioxidant properties. However, considering its low solubility, CBD delivery to the retina represents an unresolved issue.

Challenges of cannabidiol determination in emulsified cosmetics and application of solid-phase extraction followed by HPLC-UV-MS/MS.

The recent surge in popularity of cannabidiol-infused products extends beyond food and supplements to the cosmetic industry. Accurate labeling remains a significant concern, as many products fail to meet advertised cannabidiol content and/or contain psychoactive tetrahydrocannabinol above the permissible levels. In this work, we present the use of an HPLC-UV-MS/MS method for the quantification of five major cannabinoids (cannabidiol, cannabidiolic acid, tetrahydrocannabinol, tetrahydrocannabinolic acid, and cannabigerol) in oil-in-water cosmetic emulsions.

Prefrontal electrophysiological biomarkers and mechanism-based drug effects in a rat model of alcohol addiction.

Patients with alcohol use disorder (AUD) who seek treatment show highly variable outcomes. A precision medicine approach with biomarkers responsive to new treatments is warranted to overcome this limitation. Promising biomarkers relate to prefrontal control mechanisms that are severely disturbed in AUD.

Prenatal THC exposure drives sex-specific alterations in spatial memory and hippocampal excitatory/inhibitory balance in adolescent rats.

The interaction between the main psychotropic ingredient of Cannabis, Δ⁹- tetrahydrocannabinol (THC), with the endogenous cannabinoid system (ECS) is a critical and underrated issue that deserves utmost attention. The ECS, indeed, contributes to the formation and regulation of excitatory and inhibitory (E/I) neuronal networks that in the hippocampus underly spatial memory. This study explored sex-specific consequences of prenatal exposure to THC in hippocampus-dependent memory and the underlying cellular and molecular contributors of synaptic plasticity and E/I homeostasis.

Relation of native acetabular anteversion to the orientation of transverse acetabular ligament.

Background: Precise positioning of the acetabular component during total hip replacement is the key to achieving optimal implant function and ensuring long-term patient comfort. However, different anatomical variations, degenerative changes, dysplasia, and other diseases make it difficult. In this study, we discuss a method based on the three-dimensional direction of the transverse ligament, predicting native acetabular anteversion with higher accuracy.

Psilocybin administered following extinction sessions does not affect subsequent cocaine cue reinstatement in male and female rats and mice.

There are currently no pharmacological treatments for cocaine use disorder. Recently there has been a great deal of interest in the potential of psychedelic drugs such as psilocybin to treat psychiatric disorders. Human studies have indicated that a single administration of psilocybin can have long-lasting effects.

Automatic variable extraction from 3D coxal bone models for sex estimation using the DSP2 method.

Thanks to technical progress and the availability of virtual data, sex estimation methods as part of a biological profile are undergoing an inevitable evolution. Further reductions in subjectivity, but potentially also in measurement errors, can be brought by approaches that automate the extraction of variables. Such automatization also significantly accelerates and facilitates the specialist's work.

SGIP1 Deletion in Mice Attenuates Mechanical Hypersensitivity Elicited by Inflammation.

Activation of cannabinoid receptor 1 (CB1R) in the nervous system modulates the processing of acute and chronic pain. CB1R activity is regulated by desensitization and internalization. SH3-containing GRB2-like protein 3-interacting protein 1 (SGIP1) inhibits the internalization of CB1R.

Fault-Tolerant Control Based on Current Space Vectors against Total Sensor Failures.

This paper proposes a fault-tolerant control (FTC) strategy using the current space vectors to diagnose sensor failures and enhance the sustained operation of a field-oriented (FO) controlled induction motor drive (IMD). Three space vectors are established for the sensor fault diagnosis technique, including one converted from the measured currents and the other two calculated from the current estimation technique, respectively, measured and with reference speeds. A mixed mathematical model using three space vectors and their components is proposed to accurately determine the fault condition of each sensor in the motor drive.

Ambient ionization mass spectrometry provides screening of selective androgen receptor modulators.

Ambient ionization mass spectrometry allows for analysis of samples in their natural state, i.e., with no sample pre-treatment.

Label-free SERS-ML detection of cocaine trace in human blood plasma.

The widespread consumption of cocaine poses a significant threat to modern society. The most effective way to combat this problem is to control the distribution of cocaine, based on its accurate and sensitive detection. Here, we proposed the detection of cocaine in human blood plasma using a combination of surface enhanced Raman spectroscopy and machine learning (SERS-ML).

Small protein blockers of human IL-6 receptor alpha inhibit proliferation and migration of cancer cells.

Background: Interleukin-6 (IL-6) is a multifunctional cytokine that controls the immune response, and its role has been described in the development of autoimmune diseases. Signaling via its cognate IL-6 receptor (IL-6R) complex is critical in tumor progression and, therefore, IL-6R represents an important therapeutic target.

Methods: An albumin-binding domain-derived highly complex combinatorial library was used to select IL-6R alpha (IL-6Rα)-targeted small protein binders using ribosome display.

Engineering PD-1-targeted small protein variants for in vitro diagnostics and in vivo PET imaging.

Background: Programmed cell death 1 (PD-1) belongs to immune checkpoint proteins ensuring negative regulation of the immune response. In non-small cell lung cancer (NSCLC), the sensitivity to treatment with anti-PD-1 therapeutics, and its efficacy, mostly correlated with the increase of tumor infiltrating PD-1 lymphocytes. Due to solid tumor heterogeneity of PD-1 populations, novel low molecular weight anti-PD-1 high-affinity diagnostic probes can increase the reliability of expression profiling of PD-1 tumor infiltrating lymphocytes (TILs) in tumor tissue biopsies and in vivo mapping efficiency using immune-PET imaging.

Hexahydrocannabinol (HHC) and Δ-tetrahydrocannabinol (Δ-THC) driven activation of cannabinoid receptor 1 results in biased intracellular signaling.

The Cannabis sativa plant has been used for centuries as a recreational drug and more recently in the treatment of patients with neurological or psychiatric disorders. In many instances, treatment goals include relief from posttraumatic disorders, anxiety, or to support treatment of chronic pain. Ligands acting on cannabinoid receptor 1 (CB1R) are also potential targets for the treatment of other health conditions.

Cannabidiol and positive effects on object recognition memory in an in vivo model of Fragile X Syndrome: Obligatory role of hippocampal GPR55 receptors.

Cannabidiol (CBD), a non-psychotomimetic constituent of Cannabis sativa, has been recently approved for epileptic syndromes often associated with Autism spectrum disorder (ASD). However, the putative efficacy and mechanism of action of CBD in patients suffering from ASD and related comorbidities remain debated, especially because of the complex pharmacology of CBD. We used pharmacological, immunohistochemical and biochemical approaches to investigate the effects and mechanisms of action of CBD in the recently validated Fmr1-exon 8 rat model of ASD, that is also a model of Fragile X Syndrome (FXS), the leading monogenic cause of autism.

Synthesis and absolute configuration of cyclic synthetic cathinones derived from α-tetralone.

The emergence of new synthetic cathinones continues to be a matter of public health concern. In fact, already known products (drugs) are being rapidly replaced by new structurally related alternatives, whereby modifications in the basic cathinone structure are used by manufacturers to circumvent the legislation. On the other hand, some derivatives of synthetic cathinones represent important pharmaceuticals with antidepressant properties.

Methamphetamine Removal from Aquatic Environments by Magnetic Microrobots with Cyclodextrin Chiral Recognition Elements.

The growing consumption of drugs of abuse together with the inefficiency of the current wastewater treatment plants toward their presence has resulted in an emergent class of pollutants. Thus, the development of alternative approaches to remediate this environmental threat is urgently needed. Microrobots, combining autonomous motion with great tunability for the development of specific tasks, have turned into promising candidates to take on the challenge.

Structural, Biochemical, and Computational Characterization of Sulfamides as Bimetallic Peptidase Inhibitors.

The sulfonamide function is used extensively as a general building block in various inhibitory scaffolds and, more specifically, as a zinc-binding group (ZBG) of metalloenzyme inhibitors. Here, we provide biochemical, structural, and computational characterization of a metallopeptidase in complex with inhibitors, where the mono- and bisubstituted sulfamide functions are designed to directly engage zinc ions of a bimetallic enzyme site. Structural data showed that while monosubstituted sulfamides coordinate active-site zinc ions via the free negatively charged amino group in a canonical manner, their bisubstituted counterparts adopt an atypical binding pattern divergent from expected positioning of corresponding tetrahedral reaction intermediates.

Psilocybin-induced default mode network hypoconnectivity is blunted in alcohol-dependent rats.

Alcohol Use Disorder (AUD) adversely affects the lives of millions of people, but still lacks effective treatment options. Recent advancements in psychedelic research suggest psilocybin to be potentially efficacious for AUD. However, major knowledge gaps remain regarding (1) psilocybin's general mode of action and (2) AUD-specific alterations of responsivity to psilocybin treatment in the brain that are crucial for treatment development.

Solid-state vibrational circular dichroism: Methodology and application for amphetamine derivatives.

Amphetamine derivatives are considered most seized substances worldwide. In this study, solid-state vibrational circular dichroism (VCD) measurements of enantiomerically pure substances were performed for spectroscopic discrimination between (S)- and (R)-enantiomers. First, we have developed a universal experimental approach to obtain reliable and reproducible solid-state VCD spectra.

Secretion and surface display of binders of IL-23/IL-17 cytokines and their receptors in Lactococcus lactis as a therapeutic approach against inflammation.

The cytokine IL-23 activates the IL-23 receptor (IL-23R) and stimulates the differentiation of naïve T helper (Th) cells into a Th17 cell population that secretes inflammatory cytokines and chemokines. This IL-23/Th17 proinflammatory axis drives inflammation in Crohn's disease and ulcerative colitis and represents a therapeutic target of monoclonal antibodies. Non-immunoglobulin binding proteins based on the Streptococcus albumin-binding domain (ABD) provide a small protein alternative to monoclonal antibodies.

CBD enhances the cognitive score of adolescent rats prenatally exposed to THC and fine-tunes relevant effectors of hippocampal plasticity.

An altered neurodevelopmental trajectory associated with prenatal exposure to ∆-9-tetrahydrocannabinol (THC) leads to aberrant cognitive processing through a perturbation in the effectors of hippocampal plasticity in the juvenile offspring. As adolescence presents a unique window of opportunity for "brain reprogramming", we aimed at assessing the role of the non-psychoactive phytocannabinoid cannabidiol (CBD) as a rescue strategy to temper prenatal THC-induced harm. To this aim, Wistar rats prenatally exposed to THC (2 mg/kg s.