Preclinical liver toxicity models: Advantages, limitations and recommendations.

Experimental animal models are crucial for elucidating the pathophysiology of liver injuries and for assessing new hepatoprotective agents. Drugs and chemicals such as acetaminophen, isoniazid, valproic acid, ethanol, carbon tetrachloride (CCl), dimethylnitrosamine (DMN), and thioacetamide (TAA) are metabolized by the CYP2E1 enzyme, producing hepatotoxic metabolites that lead to both acute and chronic liver injuries. In experimental settings, acetaminophen (centrilobular necrosis), carbamazepine (centrilobular necrosis and inflammation), sodium valproate (necrosis, hydropic degeneration and mild inflammation), methotrexate (sinusoidal congestion and inflammation), and TAA (centrilobular necrosis and inflammation) are commonly used to induce various types of acute liver injuries.

Breakfast Skipping and Determinant Factors among Moroccan School Adolescents (12-19 Years): The Case of Beni Mellal City.

Introduction: Breakfast skipping is an unhealthy eating behavior reportedly common among adolescents. The aim of the present study was to determine the prevalence and factors associated with breakfast skipping among schoolchildren aged 12-19 years in Beni Mellal city, Morocco, and to assist in the design of interventions to improve breakfast consumption habits of school-aged children in this region.

Methods: A school-based cross-sectional study was carried out.

Fibrotic liver extracellular matrix induces cancerous phenotype in biomimetic micro-tissues of hepatocellular carcinoma model.

Background: Despite considerable advancements in identifying factors contributing to the development of hepatocellular carcinoma (HCC), the pathogenesis of HCC remains unclear. In many cases, HCC is a consequence of prolonged liver fibrosis, resulting in the formation of an intricate premalignant microenvironment. The accumulation of extracellular matrix (ECM) is a hallmark of premalignant microenvironment.

Wharton's Jelly mesenchymal stem cell-derived extracellular vesicles induce liver fibrosis-resolving phenotype in alternatively activated macrophages.

The potential of extracellular vesicles (EVs) isolated from mesenchymal stromal cells in guiding macrophages toward anti-inflammatory immunophenotypes, has been reported in several studies. In our study, we provided experimental evidence of a distinctive effect played by Wharton Jelly mesenchymal stromal cell-derived EVs (WJ-EVs) on human macrophages. We particularly analyzed their anti-inflammatory effects on macrophages by evaluating their interactions with stellate cells, and their protective role in liver fibrosis.

Surface Modification of Dentin Powder With Alginate and Evaluation of Its Effects on the Viability and Proliferation of Dental Pulp Stem Cells (In Vitro), Its Biocompatibility (In Vivo).

Introduction: This study aimed to synthesize dentin powder surface modified with alginate, a potential substance for dental pulp regeneration, and evaluate its effects on the viability and proliferation of human dental pulp stem cells in vitro and its biocompatibility in vivo.

Methods: In the in vitro phase, dentin powder was synthesized in 3 size groups (150-250 μm, 250-500 μm, and 500-1000 μm) after demineralization and atelopeptidization which is used to remove dentin collagen telopeptides and eliminate host immune response. Surface modification with alginate was performed and followed by field-emission scanning electron microscopy, energy dispersive X-ray spectroscopy, and cell viability and proliferation testing for 14 days with human dental pulp stem cells studied.

Expansion of human allogeneic liver-derived progenitor cells for liver regenerative therapy in serum-free culture conditions.

Human allogeneic liver-derived progenitor cells (HALPCs) display advanced ability to differentiate into hepatocyte-like cells and exhibit potent immunomodulatory, anti-inflammatory, and anti-fibrotic properties. HALPCs have been successfully manufactured under good manufacturing practice (GMP) and are currently in clinical development. A previous phase 2a trial demonstrated the safety of peripheral intravenous infusions of HALPCs and preliminary evidence of the cells' properties to restore liver function in patients with acute-on-chronic liver failure (ACLF), thus potentially improving their survival.

Immune regulation and therapeutic application of T regulatory cells in liver diseases.

CD4 CD25 FOXP3 T regulatory cells (Tregs) are a subset of the immunomodulatory cell population that can inhibit both innate and adaptive immunity by various regulatory mechanisms. In hepatic microenvironment, proliferation, plasticity, migration, and function of Tregs are interrelated to the remaining immune cells and their secreted cytokines and chemokines. In normal conditions, Tregs protect the liver from inflammatory and auto-immune responses, while disruption of this crosstalk between Tregs and other immune cells may result in the progression of chronic liver diseases and the development of hepatic malignancy.

Impact of glyphosate-based herbicide exposure through maternal milk on offspring's antioxidant status, neurodevelopment, and behavior.

Glyphosate-based Herbicide (GBH) is a widely used pesticide that functions as a broad-spectrum, non-selective herbicide. Despite advanced research to describe the neurotoxic potential of GBH, the harmful effects on maternal behavior and neurodevelopment of offspring remain unclear. This study was conducted to highlight the effects of GBH on the antioxidant system, anxiety traits, social interaction, and cognitive and sensorimotor functions in pups exposed to 25 or 50 mg/l daily via their mother's milk.

The immunogenic profile and immunomodulatory function of mesenchymal stromal / stem cells in the presence of Ptychotis verticillata.

Mesenchymal stromal/stem cells (MSCs) are considered to be a promising immunotherapeutic tool due to their easy accessibility, culture expansion possibilities, safety profile, and immunomodulatory properties. Although several studies have demonstrated the therapeutic effects of MSCs, their efficacy needs to be improved while also preserving their safety. It has been suggested that cell homeostasis may be particularly sensitive to plant extracts.

Sex-specific neurobehavioral and biochemical effects of developmental exposure to Malathion in offspring mice.

Malathion is an organophosphate pesticide (OP) commonly used in agriculture, industry, and veterinary medicine. Sex is a crucial factor in responding to neurotoxicants, yet the sex-specific effects of OP exposure, particularly neurological impairments following chronic low-level exposure remains limited. Our study aims to evaluate the neurobehavioral and biochemical effects of developmental exposure to Malathion across sexes.

Circulating Tumor Cells as a Promising Tool for Early Detection of Hepatocellular Carcinoma.

Liver cancer is a significant contributor to the cancer burden, and its incidence rates have recently increased in almost all countries. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and is the second leading cause of cancer-related deaths worldwide. Because of the late diagnosis and lack of efficient therapeutic modality for advanced stages of HCC, the death rate continues to increase by ~2-3% per year.

Amniotic Membrane and Its Derivatives: Novel Therapeutic Modalities in Liver Disorders.

The liver is a vital organ responsible for metabolic and digestive functions, protein synthesis, detoxification, and numerous other necessary functions. Various acute, chronic, and neoplastic disorders affect the liver and hamper its biological functions. Most of the untreated liver diseases lead to inflammation and fibrosis which develop into cirrhosis.

(-)-Epigallocatechin-3-gallate induced apoptosis by dissociation of c-FLIP/Ku70 complex in gastric cancer cells.

Anti-cancer properties of (-)-epigallocatechin-3-gallate (EGCG) are mediated via apoptosis induction, as well as inhibition of cell proliferation and histone deacetylase. Accumulation of stabilized cellular FLICE-inhibitory protein (c-FLIP)/Ku70 complex in the cytoplasm inhibits apoptosis through interruption of extrinsic apoptosis pathway. In this study, we evaluated the anti-cancer role of EGCG in gastric cancer (GC) cells through dissociation of c-FLIP/Ku70 complex.

Senescence and senotherapies in biliary atresia and biliary cirrhosis.

Background: Premature senescence occurs in adult hepatobiliary diseases and worsens the prognosis through deleterious liver remodeling and hepatic dysfunction. Senescence might also arises in biliary atresia (BA), the first cause of pediatric liver transplantation. Since alternatives to transplantation are needed, our aim was to investigate premature senescence in BA and to assess senotherapies in a preclinical model of biliary cirrhosis.

Premature senescence of the liver in Alagille patients.

Introduction: Alagille syndrome (ALGS) is an autosomal dominant disease characterized by a multisystem involvement including bile duct paucity and cholestasis, caused by JAG1 or NOTCH2 mutations in most of the cases. Jagged1-Notch2 interactions are known to be crucial for intrahepatic biliary tract development, but the Notch signaling pathway is also involved in the juxtacrine transmission of senescence and in the induction and modulation of the senescence-associated secretory phenotype (SASP).

Aim: Our aim was to investigate premature senescence and SASP in ALGS livers.

Cell and cell-derivative-based therapy for liver diseases: current approaches and future promises.

Introduction: According to the recent updates from World Health Organization, liver diseases are the 12th most common cause of mortality. Currently, orthotopic liver transplantation (OLT) is the most effective and the only treatment for end-stage liver diseases. Owing to several shortcomings like finite numbers of healthy organ donors, lifelong immunosuppression, and complexity of the procedure, cell and cell-derivatives therapies have emerged as a potential therapeutic alternative for liver diseases.

Anxiety and Associated Factors during the COVID-19 Pandemic Confinement in the Moroccan Adult Celiac Disease Population.

Introduction: The widespread lockdown due to the COVID-19 pandemic was insured by Moroccan authorities in early 2020 to preserve the health of citizens. The lockdown and the pandemic imposed psychological effects on the population including anxiety. Celiac disease (CeD), a chronic disease among the most common inflammatory intestinal disorders, has been linked to adult emotional disturbances.

Deciphering the possible reciprocal loop between hepatic stellate cells and cancer cells in the tumor microenvironment of the liver.

Activated hepatic stellate cells (HSCs)/myofibroblasts are the important sources of cancer-associated fibroblasts in the liver tumor microenvironment (TME). The crosstalk between activated HSCs and tumor cells mediates HCC progression, metastasis, tumor cell survival, angiogenesis and chemoresistance. In TME, HCC cells secrete various soluble factors responsible for the phenotypic activation of quiescent HSCs.

The global downregulation of protein synthesis observed during hepatogenic maturation is associated with a decrease in TOP mRNA translation.

Translational regulation is of paramount importance for proteome remodeling during stem cell differentiation at both the global and the transcript-specific levels. In this study, we characterized translational remodeling during hepatogenic differentiation of induced pluripotent stem cells (iPSCs) by polysome profiling. We demonstrate that protein synthesis increases during exit from pluripotency and is then globally repressed during later steps of hepatogenic maturation.

Isolation of fecal from fresh strawberries () in Iran.

Background And Objectives: Microbial safety of the fresh fruits is a global concern. The production of strawberry () in Iran has grown 4.5% from 2016 to 2019.

Intercellular communication among liver cells in the perisinusoidal space of the injured liver: Pathophysiology and therapeutic directions.

Hepatic stellate cells (HSCs) in the perisinusoidal space are surrounded by hepatocytes, liver sinusoidal endothelial cells, Kupffer cells, and other resident immune cells. In the normal liver, HSCs communicate with these cells to maintain normal liver functions. However, after chronic liver injury, injured hepatocytes release several proinflammatory mediators, reactive oxygen species, and damage-associated molecular patterns into the perisinusoidal space.

The impact of sociodemographic characteristics on diagnosis and access to disease-modifying treatment for patients with multiple sclerosis in Morocco.

Objective: This study aims to determine the link between sociodemographic factors, diagnosis, and access to disease-modifying treatment for patients with multiple sclerosis (MS) in Morocco.

Methods: This study concerned a sample of 520 patients representing seven regions of Morocco. We obtained data from the patient record registers, the patient's files, and a questionnaire.