Argania spinosa Leaves and Branches: Antiaggregant, Anticoagulant, Antioxidant Activities and Bioactive Compounds Quantification

Thrombocytes, also known as platelets, are crucial in maintaining the balance between blood clotting. Platelet hyperactivity and oxidative stress are the primary factors contributing to cardiovascular complications. Antithrombotic therapy remains one of the most effective treatments, but various potential side effects hinder its effectiveness, including the risk of haemorrhage. Intense research has been conducted on medicinal plants to discover the natural antithrombotic compounds. Argania spinosa, commonly known as the argan tree or argan oil tree, is a native species of southwestern Morocco. This study evaluated the primary and secondary hemostasis and antioxidant activity of leaf and branch aqueous extracts of A. spinosa and also assessed the phytochemical composition of these extracts. Platelet aggregation assay was performed using washed platelets stimulated with thrombin. For plasmatic coagulation, activated partial thromboplastin time and prothrombin time were measured using the poor plasma method. Bleeding time was evaluated by inducing bleeding at the tip of a mouse tail. The antioxidant activity of the extracts was determined through the DPPH, β-carotene, and FRAP methods. The presence or absence of the secondary metabolites was carried out with the help of specific reagents, and the quantitative analysis was carried out using spectrophotometric and colorimetric methods. The study results revealed the presence of phenols, total flavonoids, cardiac glycosides, tannins, and coumarins type of secondary metabolites in both types of aqueous extracts and a higher concentration of these was recorded in the leaves extracts. Both aqueous extracts significantly reduced in vitro thrombin-induced platelet aggregation, extended tail bleeding time, prolonged activated partial thromboplastin and prothrombin time and exhibited remarkable antioxidant activity. The leaf extract of A. spinosa exerts significant effects against thrombotic manifestations and could be a promising source of new antithrombotic compounds

Étude de la qualité bactériologique et physico-chimique des eaux de certains puits et sources par l’utilisation d’une analyse en composantes principales (ACP): Une étude de cas de la région de Meknès (MAROC)

The present study aims to investigate the impact of anthropogenic factors on the quality of groundwater in some wells and springs in the region of Meknes, used for the various purpose by the local population. This work was conducted for a duration of 6 months by monthly withdrawal from February to July 2013. The main physico-chemical and biological components of water quality have been measured and a principal component analysis (PCA) was performed based on the average values ​​of each parameter, it was able to reveal the existence of a relatively strong spatial variation of these descriptors, making it appear four groups of very well differentiated and unequal stations: the first two groups together five wells and two springs provide a good quality water or slightly polluted and the last two which contain the other wells where the water is very polluted.La présente étude a pour objectif d’étudier l’impact des facteurs anthropiques sur la qualité des eaux souterraines de certains puits et sources de la région de Meknès, utilisées à différents usage par la population locale. Ce travail a été réalisé pendant une durée de 6 mois, par des prélèvements mensuels de Février à juillet 2013. Les principales composantes physico-chimiques et bactériologiques de la qualité de l’eau ont donc été mesurées puis une analyse en composantes principales (ACP) a été réalisée à partir des valeurs moyennes de chaque paramètre ; on a pu révéler ainsi l’existence d’une variation spatiale relativement marquée de ces descripteurs, faisant apparaître quatre groupes de stations très inégaux et bien différenciés : les deux premiers groupes rassemblent 5 puits et les deux sources fournissent une eau de bonne qualité ou légèrement polluée et les deux derniers qui contiennent les autres puits dont l’eau est très polluée

Poly (ADP-ribose) polymerase-1 is a key mediator of liver inflammation and fibrosis.

Poly (ADP-ribose) polymerase 1 (PARP-1) is a constitutive enzyme, the major isoform of the PARP family, which is involved in the regulation of DNA repair, cell death, metabolism, and inflammatory responses. Pharmacological inhibitors of PARP provide significant therapeutic benefits in various preclinical disease models associated with tissue injury and inflammation. However, our understanding the role of PARP activation in the pathophysiology of liver inflammation and fibrosis is limited. In this study we investigated the role of PARP-1 in liver inflammation and fibrosis using acute and chronic models of carbon tetrachloride (CCl4 )-induced liver injury and fibrosis, a model of bile duct ligation (BDL)-induced hepatic fibrosis in vivo, and isolated liver-derived cells ex vivo. Pharmacological inhibition of PARP with structurally distinct inhibitors or genetic deletion of PARP-1 markedly attenuated CCl4 -induced hepatocyte death, inflammation, and fibrosis. Interestingly, the chronic CCl4 -induced liver injury was also characterized by mitochondrial dysfunction and dysregulation of numerous genes involved in metabolism. Most of these pathological changes were attenuated by PARP inhibitors. PARP inhibition not only prevented CCl4 -induced chronic liver inflammation and fibrosis, but was also able to reverse these pathological processes. PARP inhibitors also attenuated the development of BDL-induced hepatic fibrosis in mice. In liver biopsies of subjects with alcoholic or hepatitis B-induced cirrhosis, increased nitrative stress and PARP activation was noted. CONCLUSION: The reactive oxygen/nitrogen species-PARP pathway plays a pathogenetic role in the development of liver inflammation, metabolism, and fibrosis. PARP inhibitors are currently in clinical trials for oncological indications, and the current results indicate that liver inflammation and liver fibrosis may be additional clinical indications where PARP inhibition may be of translational potential

Proyecto para la Inserción Laboral de las Personas en Situación de Exclusión Socioresidencial Grave: creación de un servicio/sección de acompañamiento y apoyo al empleo en el Centro Social San Antonio de Zaragoza

El presente proyecto de intervencion que hemos documentado consta de un diagnostico social previo a cerca de la situacion socio economica de las personas en situación de exclusión socioresidencial grave y proyecto de intervención para su insercion en el mercado laboral

Interleukin-17 Contributes to the Pathogenesis of Autoimmune Hepatitis through Inducing Hepatic Interleukin-6 Expression

T helper cells that produce IL-17 (Th17 cells) have recently been identified as the third distinct subset of effector T cells. Emerging data suggests that Th17 cells play an important role in the pathogenesis of many liver diseases by regulating innate immunity, adaptive immunity, and autoimmunity. In this study, we examine the role and mechanism of Th17 cells in the pathogenesis of autoimmune hepatitis (AIH). The serum levels of IL-17 and IL-23, as well as the frequency of IL-17+ cells in the liver, were significantly elevated in patients with AIH, compared to other chronic hepatitis and healthy controls. The hepatic expressions of IL-17, IL-23, ROR-γt, IL-6 and IL-1β in patients with AIH were also significantly increased and were associated with increased inflammation and fibrosis. IL-17 induces IL-6 expression via the MAPK signaling pathway in hepatocytes, which, in turn, may further stimulate Th17 cells and forms a positive feedback loop. In conclusion, Th17 cells are key effector T cells that regulate the pathogenesis of AIH, via induction of MAPK dependent hepatic IL-6 expression. Blocking the signaling pathway and interrupting the positive feedback loop are potential therapeutic targets for autoimmune hepatitis

IL-6-Mediated Activation of Stat3α Prevents Trauma/Hemorrhagic Shock-Induced Liver Inflammation

Trauma complicated by hemorrhagic shock (T/HS) is the leading cause of morbidity and mortality in the United States for individuals under the age of 44 years. Initial survivors are susceptible to developing multiple organ failure (MOF), which is thought to be caused, at least in part, by excessive or maladaptive activation of inflammatory pathways. We previously demonstrated in rodents that T/HS results in liver injury that can be prevented by IL-6 administration at the start of resuscitation; however, the contribution of the severity of HS to the extent of liver injury, whether or not resuscitation is required, and the mechanism(s) for the IL-6 protective effect have not been reported. In the experiments described here, we demonstrated that the extent of liver inflammation induced by T/HS depends on the duration of hypotension and requires resuscitation. We established that IL-6 administration at the start of resuscitation is capable of completely reversing liver inflammation and is associated with increased Stat3 activation. Global assessment of the livers showed that the main effect of IL-6 was to normalize the T/HS-induced inflammation transcriptome. Pharmacological inhibition of Stat3 activity within the liver blocked the ability of IL-6 to prevent liver inflammation and to normalize the T/HS-induced liver inflammation transcriptome. Genetic deletion of a Stat3β, a naturally occurring, dominant-negative isoform of the Stat3, attenuated T/HS-induced liver inflammation, confirming a role for Stat3, especially Stat3α, in preventing T/HS-mediated liver inflammation. Thus, T/HS-induced liver inflammation depends on the duration of hypotension and requires resuscitation; IL-6 administration at the start of resuscitation reverses T/HS-induced liver inflammation, through activation of Stat3α, which normalized the T/HS-induced liver inflammation transcriptome

Rôle de la protéine Gas6 dans le foie en régénération à partir d'hépatocytes ou à partir de cellules précurseurs (les cellules ovales)

Lors de la régénération hépatique, les cellules étoilées du foie (CEF) s'activent en myofibroblastes (CEF/MFB) et jouent un rôle clé dans le remodelage matriciel et la réparation tissulaire. Une hépatite induite chez le rat, par l'injection de tétrachlorure de carbone (CC14), entraîne une induction de l'expression de la protéine Gas6 dans les CEF/MFB ainsi que dans les macrophages inflammatoires qui infiltrent les zones centrolobulaires nécrosées. Nous avons montré un effet anti-apoptodique de Gas6 sur des CEF et des CEF/MFB en culture. Après une injection de CC14 à des souris déficientes pour Gas6, nous avons observé un retard dans la réparation tissulaire, étroitement lié à un défaut d'accumulation de CEF/MFB et à un recrutement très limité de monocytes inflammatoires impliqués dans l'activation des CEF en CEF/MFB. In vitro, des propriétés chimiotactiques de Gas6 sur les monocytes circulants ont été mises en évidence. Lorsque la prolifération des hépatocytes résiduels est altérée, le foie régénère à partir de cellules précurseurs intra-hépatiques : les cellules ovales. Dans ce type de régénération, induite chez le rat après une hépatectomie partielle associée à un traitement à l'acétylaminofluorène, les cellules ovales qui s'accumulent transitoirement dans les zones périportales, expriment fortement la protéine Gas6. In vitro, nous avons aussi montré un effet anti-apoptotique de Gas6 sur les cellules WB-F344 utilisées comme modèle de cellules ovales. Gas6 joue donc un rôle dans la régénération hépatique en favorisant le recrutement de cellules inflammatoires, ainsi que l'accumulation transitoire de CEF/MFB et de cellules ovales, en les protégeant contre l'apoptose.In liver regeneration, hepatic stellate cells (HSC) activate into myofibroblasts (HSC/MFB) and play a key role in matrix remodelling and tissue repair. Carbon tetrachloride (CC14)-induced hepatitis leads to Gas6 protein induction in HSC/MFB as well as in infiltrated inflammatory monocytes in centrilobular necrotic areas. An anti-apoptotic effect of Gas6 was shown in cultured HSC and HSC/MFB. In Gas6-deficient mice after CC14-injection, we observed a delay in tissue repair associated with a defect in HSC/MFB accumulation, and a small number of recruited inflammatory monocytes involved in HSC activation into HSC/MFB. In vitro, chemotactic properties of Gas6 were shown on peripheral blood monocytes. When the proliferation of residual hepatocytes is altered, liver regeneration occurs from intra-hepatic precursor cells : the oval cells. In such a regeneration obtained in the rat after partial hepatectomy associated with an acetylaminofluorene treatment, we observed a periportal accumulation of oval cells, which also expressed Gas6. In vitro, we also showed the anti-apoptotic effect of Gas6 on WB-F344 cells used as an oval cell model. Thus, Gas6 plays a role in liver regeneration by favouring inflammatory cell recruitment, and the accumulation of HSC/MFB and oval cells by protecting them against apoptosis.PARIS12-CRETEIL BU Multidisc. (940282102) / SudocSudocFranceF

Novel insights into the impact of liver inflammatory responses on primary liver cancer development

Primary liver cancers rank among the deadliest cancers worldwide and often develop in patients with chronic liver diseases in an inflammatory context. This review highlights recent reports on the mechanisms of inflammatory-mediated hepatic cell transformation that trigger the tumorigenic process (initiation steps) and the impact of the immune response favoring tumor cell expansion (progression steps). Several cytokines, namely interleukin (IL)-6, IL-17, IL-1beta, and tumor necrosis factor-alpha, have been described to play a prominent role in the initiation of liver cancers. Additionally, inflammation contributes to cancer progression by favoring tumor escape from anti-tumor immune response, angiogenesis, and metastasis through tumor growth factor-beta and matrix metalloprotease upregulation. These recent studies allowed the development of novel therapeutic strategies aiming at regulating liver inflammation. These strategies are based on the use of anti-inflammatory agents, antibodies targeting immune checkpoint molecules such as programmed death ligand 1 and molecules targeting angiogenic factors, metastasis key factors, and microRNAs involved in tumor development. This review aims at summarizing the recent studies reporting different mechanisms by which the liver inflammatory responses could contribute to liver cancer development