This study evaluated the anti-inflammatory and analgesic potential of a novel 1,5-benzodiazepine derivative (MAL) using in vivo models and in silico molecular docking analysis. A total of 264 adult male Swiss albino mice were used for standard pharmacological investigations. MAL was administered at doses of 5, 10, 25, and 50 mg/kg. Diazepam (DZP), diclofenac, and acetaminophen (APAP) were used as reference drugs. Anti-inflammatory activity was assessed using carrageenan-induced paw edema, the air pouch model, and Evans blue–induced vascular permeability. Histopathological analysis was performed to evaluate tissue edema, leukocyte, and neutrophil infiltration. Analgesic effects were evaluated using tail-flick, hot plate, and acetic acid-induced writhing assays. Molecular docking studies were conducted to predict binding interactions of MAL with the α1A-adrenergic receptor (8THL) and COX-2 (3LN1), with results expressed as mean ± SEM. MAL significantly reduced paw edema, with maximal inhibition at 25 mg/kg (43.41

Anxiety and depressive disorders constitute a public health concern with a high negative impact on patients' quality of life. These disorders are among the prevalent neuropsychiatric conditions significantly contributing to the global burden. Although the precise mechanisms underlying the development of anxiety- and depressive-like behaviors remain incompletely understood, increasing evidence indicates that these disorders arise from complex and multifactorial processes involving dysfunction across multiple body organs. The gut microbiota (GM) seem to play certain role in developing of these conditions, as supported by studies demonstrating its influence on brain function and behavior. Indeed, several studies have recently reported that alterations in GM composition and function are linked with immune system dysregulation (inflammation/neuroinflammation) and subsequently influence brain pathways and systems, including neurotransmitters, the hypothalamic-pituitary-adrenal axis (HPA), and neurotrophic factors. Also, therapeutic agents targeting gut dysbiosis (GD) have yielded significant results. This review summarizes the role of GM in the pathophysiology of anxiety and depressive behaviors, its interaction with some psychotropic drugs, and its potential use as a therapeutic target for these conditions.Clinical trial number: Not applicable.

Benzodiazepines (BZDs) are widely used but are often associated with significant side effects such as amnesia, dependence, and withdrawal syndrome, prompting the search for safer alternatives. The current study aimed to assess the possible toxic effects of a novel 1,5-BZD derivative, which we named MAL. In silico analysis showed that MAL binds to the GABA-A receptor with a binding energy of -8.9 kcal/mol, and to its α1, β2, and γ2 subunits with binding energies of -7.6, -7.5, and -7.6 kcal/mol, respectively, indicating strong receptor affinity. To explore the safety of MAL, toxicological testing was conducted in laboratory animals in accordance with internationally accepted guidelines. Acute toxicity was evaluated by a single oral administration of 2 g/kg body weight to male mice, monitored over 14 days. Since BZDs are typically prescribed for up to two weeks in clinical practice, a 28-day repeated-dose toxicity study was also conducted. Mice received MAL (5, 25, 50, and 100 mg/kg) daily for 28 days to evaluate potential toxic effects. No adverse effects were observed on body weight gain, relative organ weights, or food and water consumption. Histological examination of major organs revealed no abnormalities, and biochemical analyses confirmed the absence of hepatotoxicity or nephrotoxicity. Additionally, we present ProTox, a comprehensive, open-source webserver designed for in silico toxicity prediction. In this study, ProTox predicted an oral LD50 of MAL at 3 g/kg. Based on the Globally Harmonized System (GHS) of classification, this places MAL in Category V. These findings support the potential safety of MAL for pharmaceutical formulations.

Although COVID-19 primarily affects the respiratory system, many patients experience gastrointestinal symptoms, suggesting a role for the gut microbiota in disease pathogenesis. To explore this, we performed shotgun metagenomic sequencing on stool samples from 200 COVID-19 patients and 102 healthy controls in Morocco and France. Despite geographic differences in microbiota composition, patients with COVID-19 in both continents exhibited significant gut microbiota alterations, which were more pronounced in severe cases, with similar features compared with controls. Functional pathways, including L-Tryptophan biosynthesis, were disrupted, particularly in patients with severe disease. Machine learning models accurately predicted disease severity based on gut microbial profiles in the Moroccan cohort, though not in the French cohort. These results highlight consistent microbiota changes associated with COVID-19 and support a potential link between gut dysbiosis and disease severity.

Despite the prevalence of fucosylated IgG in plasma, specific IgGs with low core fucosylation sporadically emerge in response to virus infections and blood cell alloantigens. This low fucosylation of IgG is implicated in the pathogenesis of SARS-CoV-2 and dengue infections. In COVID-19, the presence of IgGs with low core fucosylation (afucosylated IgGs) targeting spike protein predicts disease progression to a severe form and actively mediates this progression. This study reveals that SARS-CoV-2 infection of megakaryocytes promotes the generation of pathogenic afucosylated anti-spike IgGs, leading to outcomes, such as pulmonary vascular thrombosis, acute lung injury, and mortality in FcγRIIa-transgenic mice. Platelets from mice injected with virus-infected human megakaryocytes express significant activation biomarkers, indicating a direct link between the immune response and platelet activation. Mice injected with virus-infected human megakaryocytes demonstrate an elevated rate of thrombus formation induced by FeCl3 (4%) and a reduction in bleeding time, emphasizing the intricate interplay of viral infection, immune response, and hemostatic complications. Treatment with inhibitors targeting FcγRIIa, serotonin, or complement anaphylatoxins of mice injected with spike-expressing MKs successfully prevents observed platelet activation, thrombus formation, and bleeding abnormalities, offering potential therapeutic strategies for managing severe outcomes associated with afucosylated IgGs in COVID-19 and related disorders.

This observational study aimed to compare various genotyping and enrichment platforms to determine the most comprehensive coverage for genome-wide association studies, specifically targeting new therapeutic approaches against coronaviruses using chloroquine. Pharmacogenomic studies have become essential for understanding individual drug responses, and optimal platform selection is critical for identifying relevant genetic variants. We developed Python scripts to assess the coverage rates of these platforms, focusing on the absorption, distribution, metabolism, and excretion (ADME) genes involved in drug absorption, distribution, metabolism, and excretion. Additionally, the PLINK tool was employed to evaluate single nucleotide polymorphisms in linkage disequilibrium with ADME variants, providing insights into the extended coverage achieved through correlation with these variants. Among the genotyping platforms analyzed, Axiom genotyping and SureSelect enrichment platforms demonstrated the most extensive coverage of the genome and key pharmacogenomic regions. These platforms effectively captured a significant proportion of ADME gene variants, which are crucial for predicting individual responses to chloroquine. The extensive coverage provided by the Axiom and SureSelect platforms supports their use in the design of pharmacogenomic studies, potentially revealing new therapeutic targets for combating coronaviruses, including through the use of chloroquine treatment. The results highlight the importance of selecting appropriate genotyping and enrichment technologies for maximizing the impact of pharmacogenomic research.

Over the past two decades, available literature on the genomics of certain neurological disorders has expanded considerably. Even though there are diverse genomic data among African people, few Africa-centric empirical studies on neurogenomics have been conducted, especially in Morocco. While genomics technologies have been widely implemented in many laboratories, their impact on understanding and improving health outcomes has been more pronounced in some fields than in others. In Morocco, genomics has significantly advanced our understanding of infectious diseases and oncology. However, its application in neurological illnesses has been more challenging. This is primarily attributed to insufficient and limited financial investment, often arising from a lack of interest and awareness in prioritizing research and development in neurology within our research policies. In this context, this study aims to explore the opportunities and possible challenges facing neurogenomics research and its implementation in Morocco, as the country is involved in genomic research. Existing challenges, including a lack of local research funding and training opportunities in neuroscience, genomics, bioinformatics, and infrastructure, are discussed. To encourage and ensure the sustainability of neurogenomics investigations across our nation, the influence of existing difficulties and potential solutions was investigated.

Received: 08 November 2022 Accepted after revision: 14 March 2023 Accepted Manuscript online:12 April 2023

More than 90% of total human plasma immunoglobulin G (IgG) is found in a fucosylated form, but specific IgGs with low core fucosylation (afucosylated IgGs) are found in response to infections with enveloped viruses and to alloantigens on blood cells. Afucosylated IgGs mediate immunopathology in severe COVID-19 and dengue fever in humans. In COVID-19, the early formation of non-neutralizing afucosylated IgG against the spike protein predicts and directly mediates disease progression to severe form. IgG lacking core fucosylation causes dramatically increased antibody-dependent cellular toxicity mediated by intense FcγR-mediated stimulation of macrophages, monocytes, natural killer cells, and platelets. The mechanism and the context within which afucosylated IgG formation occurs in response to enveloped virus antigens have remained elusive thus far in COVID-19, dengue fever, and other infections. This study demonstrates that administration of human bone marrow megakaryocytes infected by SARS-CoV-2 into the circulation of K18-hACE2 transgenic mice drives the formation of pathogenic afucosylated anti-spike IgG antibodies, and is sufficient to reproduce severe COVID-19 manifestations of pulmonary vascular thrombosis, acute lung injury, and death in mice.

Depression is a complex neuropsychiatric illness affecting millions worldwide. Furthermore, its exact cause remains uncertain. Theories include the monoamine hypothesis, changes in hormonal systems, inflammation, immune alterations, neurogenesis issues, and environmental factors. Recent research has highlighted the role of glial cells, particularly microglia and astrocytes, in depression. This chapter explores the implications of glial cells in depression, shedding light on their involvement in neuroinflammation, synaptic plasticity, and the regulation of mood-related circuits. An intricate interplay between glial cells, proinflammatory cytokines, and neuronal processes appears to underlie the etiology and progression of depression. Understanding the dynamic interactions between glial cells and neurons in the context of depression offers promising avenues for novel therapeutic interventions targeting this debilitating disorder's neuroinflammatory components.

Due to the Covid-19 pandemic Morocco had to introduce very drastic measures such as quarantine, social distancing or massive restriction of public life in order to prevent the collapse of the health system due to the rapid spread of the disease. This descriptive and analytical study was conducted during strict quarantine among Moroccan adults aged 18 to 63 years (n=990)to examine the psychological impact of Covid-19 pandemic in Moroccan population. They responded to online survey including three items; socio-demographic status, health status and a modified version of Hospital Anxiety and Depression scale (HADs). We found a high prevalence of anxiety 40.5% and depression 28,9%. Young participants aged below 30 were more likely to have anxiety (59,1%) and depression symptoms (50%). The prevalence of this symptoms was higher in women (66,8%) compared to men. Individuals with higher education degree tend to be more anxious (65,1%) and depressed (63,3%) compared by those with secondary (26,7% anxious, 28% depressed) and elementary education level (8,2% anxious, 8,7% depressed). Covid-19 pandemic caused a new economical, medical and social conditions, altered the quality of life of Moroccan population and caused a higher prevalence mental health like fear, anxiety and depression.

Platelets are hyperactivated in coronavirus disease 2019 (COVID-19). However, the mechanisms promoting platelet activation by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not at high viral concentrations per 10 platelets; platelet the

The pathogenesis of inflammatory bowel diseases (IBD), representing chronic and relapsing-remitting disorders of the gastrointestinal tract, encompasses Crohn's disease (CD) and ulcerative colitis.[1] [2] Although the cause and mechanisms of both conditions remain unknown, mounting evidence suggests that gut tissue injury is not exclusively the result of a dysregulated immune response, but also involves the active participation of multiple non-immune cellular systems.[3] [4]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is spreading throughout the world at an alarming rate.[1] Severe disease is characterized by acute respiratory distress syndrome (ARDS), frequently associated with thrombotic complications.[2] [3] Some studies report the presence of platelets in thrombi found in multiple organs of COVID-19 autopsy cases.[4] [5] Moreover, hyperreactive platelets and overwhelming generation of inflammatory cytokines (i.e., a condition also known as “cytokine storm”) are frequent in COVID-19 patients.[6] [7] [8] [9] [10] [11] Furthermore, SARS-CoV-2 ribonucleic acid (RNA) could be detected in platelets of COVID-19 patients.[6] [10] [12] Despite these findings suggesting a role for platelets in the pathophysiology of COVID-19, the mechanisms of increased thrombotic events remain not completely elucidated.

Ulcerative colitis (UC) and Crohn's disease (CD) are chronic and multifactorial diseases that affect the intestinal tract, both characterized by recurrent inflammation of the intestinal mucosa, resulting in abdominal pain, diarrhea, vomiting and, rectal bleeding. Inflammatory bowel diseases (IBD) regroup these two disorders. The exact pathological mechanism of IBD remains ambiguous and poorly known. In genetically predisposed patients, defects in intestinal mucosal barrier are due to an uncontrolled inflammatory response to normal flora. In addition to the genetic predisposition, these defects could be triggered by environmental factors or by a specific lifestyle which is widely accepted as etiological hypothesis. The involvement of the CD40/CD40L platelet complex in the development of IBD has been overwhelmingly demonstrated. CD40L is climacteric in cell signalling in innate and adaptive immunity, the CD40L expression on the platelet cell surface gives them an immunological competence. The IL-1, a major inflammation mediator could be involved in different ways in the development of IBD. Here, we provide a comprehensive review regarding the role of platelet CD40/CD40L in the pathophysiological effect of IL-1 in the development of Crohn's disease (CD). This review could potentially help future approaches aiming to target these two pathways for therapeutic purposes and elucidate the immunological mechanisms driving gut inflammation.

Since the emergence of SARS-CoV-2 in China in December 2019 and the subsequent coronavirus disease 2019 (COVID-19), and as a consequence of the rapid spread worldwide, the World Health Organization (WHO) declared the outbreak a serious public health emergency of international concern.[1]

Inflammatory bowel disease (IBD) is a group of chronic disorders that includes two main disease forms, Crohn's disease, and ulcerative colitis. The understanding of the intestinal inflammation occurring in IBD has been immeasurably advanced by the development of the now numerous murine models of intestinal inflammation. The usefulness of this research tool in IBD arises from a convergence of underlying genetic susceptibility, immune system dysfunction, environmental factors, and shifts in gut microbiota. Due to the multifactorial feature of these diseases, different animal models have been used to investigate the underlying mechanisms and develop potential therapeutic strategies. The results of preclinical efficacy studies often inform the progression of therapeutic strategies. This review describes the distinct feature and limitations of each murine IBD model and discusses the previous and current lessons from the IBD models.

Les maladies cardiovasculaires (MCV) sont la première cause de mortalité dans le monde. Les plaquettes jouent un rôle majeur dans le développement de ces maladies et la mise au point d’antiplaquettaires efficaces constitue une priorité dans le cadre de la lutte contre la mortalité liée aux MCV. L’aspirine et les médicaments de la famille des thiénopyridines sont les agents antiplaquettaires les plus utilisés actuellement. Ces médicaments ciblent des voies de signalisation impliquées dans l’initiation de l’agrégation, exerçant ainsi un effet antiplaquettaire modéré. D’autres médicaments aux effets plus importants, comme les molécules dirigées contre le récepteur GPIIb/IIIa, inhibent l’agrégation plaquettaire indépendamment de la voie de signalisation initiant l’activation plaquettaire, mais ils sont associés à des complications hémorragiques majorées. Étant données les caractéristiques spécifiques de chacun de ces agents antiplaquettaires, leur prescription nécessite de prendre en compte le type d’évènement cardio-vasculaire, l’âge et les comorbidités du patient traité et, bien sûr, les effets secondaires hémorragiques potentiels de la molécule qui est prescrite. Apparaît donc la nécessité de mettre au point de nouvelles molécules ayant un effet plus ciblé, gardant une efficacité optimale, mais permettant une réduction du risque hémorragique qui constitue la principale limite des médicaments antiplaquettaires.

Spasticity is a disabling motor disorder affecting 70% of people with brain and spinal cord injury. The rate-dependent depression (RDD) of the H reflex is the only electrophysiological measurement correlated with the degree of spasticity assessed clinically in spastic patients. Several lines of evidence suggest that the mechanism underlying the H reflex RDD depends on the strength of synaptic inhibition through GABAA (GABAAR) and glycine receptors (GlyR). In adult rats with spinal cord transection (SCT), we studied the time course of the expression of GABAAR and GlyR at the membrane of retrogradely identified Gastrocnemius and Tibialis anterior motoneurons (MNs) 3, 8 and 16 weeks after injury, and measured the RDD of the H reflex at similar post lesion times. Three weeks after SCT, a significant decrease in the expression of GABAA and GlyR was observed compared to intact rats, and the H-reflex RDD was much less pronounced than in controls. Eight weeks after SCT, GlyR values returned to normal. Simultaneously, we observed a tendency to recover normal RDD of the H reflex at higher frequencies. We tested whether an anti-inflammatory treatment using methylprednisolone performed immediately after SCT could prevent alterations in GABAA/glycine receptors and/or the development of spasticity observed 3 weeks after injury. This treatment restored control levels of GlyR but not the expression of GABAAR, and it completely prevented the attenuation of RDD. These data strongly suggest that alteration of glycinergic inhibition of lumbar MNs is involved in the mechanisms underlying spasticity after SCI.