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Hepatitis B and C viruses can lead to serious complications such as hepatic fibrosis, liver cirrhosis, and hepatocellular carcinoma (HCC) and are therefore responsible for a significant portion of liver cancer cases worldwide, with over 1.3 million deaths annually. The mechanisms by which hepatitis viruses contribute to HCC include DNA integration into the host genome, metabolic reprogramming, induction of the cellular stress response pathway, and interference with tumour suppressors. HBV is a DNA virus from the Hepadnaviridae family, and HCV is an RNA virus from the Flaviviridae family. Both viruses are transmitted through contact with infected bodily fluids, such as blood or sexual fluids. It is important to get tested for hepatitis B and C and to seek treatment as early as possible to prevent the progression to liver cancer. While there is a vaccine available for Hepatitis B, there is currently no vaccine for Hepatitis C. But some natural medicines have demonstrated antiviral activity against the hepatitis B and C viruses. Therefore, it is important to explore natural alternatives for the treatment of this disease. This review aims to summarise the pathogenesis of hepatitis B and C and their link to hepatocellular carcinoma, as well as to highlight natural compounds with the potential to treat hepatitis through various mechanisms at different stages of infection. These natural compounds may offer an alternative to chemical-based medications in the treatment and control of hepatitis by inhibiting or disrupting the entry, activity, or replication of the virus within the host.

« Le web est aux bibliothèques ce qu’un marché aux puces est à la Bibllottièque du Congrès », écrivaient T. Kuny et G. Cieveland. L’extraordinaire profusion d’informations diverses répandues sur le réseau des réseaux, ainsi que leur volatilité, leurs statuts variés, leur accessibilité exceptionnelle, bouleversent les activités traditionnelles des bibliothécaires, et particulièrement la constitution et la gestion des collections, lesquelles ne se limitent plus à la seule construction d’un patrimoine matériel. Comment cette nouvelle documentation peut-elle être intégrée à l’offre des collections des bibliothèques, telle est la question qui domine le cœur de cet ouvrage. Pour y répondre, Alain Caraco, directeur des bibliothèques départementales de Savoie et Haute-Savoie puis des bibliothèques municipales de Chambéry, a réuni une équipe d’experts qui analysent, de la sélection à la conservation, en passant par le signalement et l’offre aux publics, les multiples étapes jalonnant la constitution d’une politique documentaire appliquée aux ressources d’Internet.

1. Cinq questions préalables • Pourquoi « cataloguer » les ressources d’Internet ? Parce qu’Internet est une masse informe de données hétéroclites, l’utilisateur a besoin d’outils de recherche, mais aussi de sélection. Or les catalogues sont précisément des instruments permettant de mettre de l’ordre dans une collection de documents et d’y donner accès. Au sens propre ou métaphorique, Internet doit être catalogué. • Est-ce aux bibliothèques de le faire ? On pourrait estimer que le travail est...

Réseaux des réseaux, Internet (International Network) est composé de plusieurs millions de micro-ordinateurs dans le monde reliés entre eux par les voies de télécommunication Le protocole fédérateur est TCP/IP (Transfer Control Protocol/Internet Protocol), qui gère la circulation et l’échange des données entre les systèmes fonctionnant en réseau sur l’Internet. Internet propose divers services. Les plus populaires sont le Web et la messagerie électronique. Cependant, il faut savoir qu’il exis...

Oxalobacter formigenes is an oxalate-degrading bacterium in the gut microbiota that absorbs food-derived oxalate to use this as a carbon and energy source and thereby helps reduce the risk of kidney stone formation of the host animals 1–4. The bacterial oxalate transporter OxlT uptakes oxalate from the gut to bacterial cells and excrete formate as a degradation product, with a strict discrimination from other carboxylates that serve as nutrients 5–7. Nevertheless, the underlying mechanism remains unclear. Here, we present crystal structures of oxalate-bound and ligand-free OxlT in two different conformations, occluded and outward-facing states. The oxalate binding site contains two basic residues that form salt bridges with a dicarboxylate substrate while preventing the conformational switch to the occluded state without an acidic substrate, a ‘disallowed’ state for an antiporter 8, 9. The occluded ligand-binding pocket can accommodate oxalate but not larger dicarboxylates, such as metabolic intermediates. The permeation pathways from the binding pocket are completely blocked by extensive interdomain hydrophobic and ionic interactions. Nevertheless, a molecular dynamics simulation showed that a flip of a single side chain neighbouring the substrate is sufficient to trigger the gate opening. The OxlT structure indicates the underlying metabolic interactions enabling favourable symbiosis at a molecular level.

International audience; Hereditary xerocytosis is a dominantly inherited red cell membrane disorder caused in most cases by gain-of-function mutations in PIEZO1, encoding a mechanosensitive ion channel that translates a mechanic stimulus into calcium influx. We found that PIEZO1 was expressed early in erythroid progenitor cells, and investigated whether it could be involved in erythropoiesis, besides having a role in the homeostasis of mature red cell hydration. In UT7 cells, chemical PIEZO1 activation using YODA1 repressed glycophorin A expression by 75%. This effect was PIEZO1-dependent since it was reverted using specific short hairpin-RNA knockdown. The effect of PIEZO1 activation was confirmed in human primary progenitor cells, maintaining cells at an immature stage for longer and modifying the transcriptional balance in favor of genes associated with early erythropoiesis, as shown by a high GATA2/GATAI ratio and decreased alpha/beta-globin expression. The cell proliferation rate was also reduced, with accumulation of cells in G0/G1 of the cell cycle. The PIEZO1-mediated effect on UT7 cells required calcium-dependent activation of the NFAT and ERK1/2 pathways. In primary erythroid cells, PIEZO1 activation synergized with erythropoietin to activate STATS and ERK, indicating that it may modulate signaling pathways downstream of erythropoietin receptor activation. Finally, we studied the in-vitro erythroid differentiation of primary cells obtained from 14 PIEZO1-mutated patients, from 11 families, carrying ten different mutations. We observed a delay in erythroid differentiation in all cases, ranging from mild (n=3) to marked (n=8). Overall, these data demonstrate a role for PIEZO1 during erythropoiesis, since activation of PIEZO1 both chemically and through activating mutations - delays erythroid maturation, providing new insights into the pathophysiology of hereditary xerocytosis.

Le paysage associatif français se retrouve particulièrement chez les bibliothécaires, davantage que chez les documentalistes et archivistes. Aux côtés des trois grandes associations généralistes que sont celles des bibliothécaires de France, des professionnels de l’information et de la documentation et des archivistes français, on rencontre des organisations par type d’établissement, domaine professionnel, contenu documentaire, catégorie de public ou encore dédiées à une mission précise. Regroupant tantôt des personnes physiques, tantôt des personnes morales, tantôt les deux, ces associations de quelques membres à plusieurs milliers se définissent des objectifs de défense et de promotion des professions et métiers ou établissements ; elles jouent un rôle de représentation pour leurs interlocuteurs et leur communauté professionnelle et se fondent volontiers sur des valeurs professionnelles énoncées dans des chartes ou manifestes. Elles cherchent à peser sur les décideurs. Elles favorisent la réflexion et l’échange par des publications et des rencontres. Elles n’ont pas le monopole de l’expression et de la veille dont les possibilités ont été multipliées par la révolution numérique, mais demeurent uniques dans leurs fonctions de représentation et d’action, distincte de celle des syndicats. Elles auront à le relever les défis du renouvellement générationnel permanent en trouvant les formules de large participation de leurs adhérents., Associations in France are especially representative with regards to librarians, more so than with documentalists and archivists. In addition to the three large general associations, that is librarians, information and document professionals and archivists, there are organisations according to the type of organisation, the professional activity, the type of documents, the readership or clients or to a specific organisational mission. Whether they bring together individuals or corporations, or sometimes both, these associations, big or small, define their objectives and advancement of the professions or organisations. They represent their respective memberships and communities and use the professional values outlined in their charters. They aim to influence the decision-makers. They also promote the exchange of ideas by means of publications and meetings. They have no exclusive action or stewardship that has now been further enhanced by the numeric revolution but remain, however, distinct from unions. They will have to answer to the challenges of renewal with a new generation by identifying innovative ways for their members to express their concerns.

Wilson disease is a rare inherited disorder of copper metabolism that affects liver and brain due to copper tissue accumulation. The mechanism involved is based on mutations of the ATP7B gene. Children have predominant hepatic manifestations while adult are more often diagnosed by neurological and psychiatric symptoms. However, others features are tubulopathy, articular disorders and hemolytic anemia. We report the diagnostic of Wilson disease in a 14 years old girl and her sibling after investigation of hemolytic anemia, hepatic insufficiency, and hypophosphatemia.

Rad51 is a key protein in DNA repair by homologous recombination and an important target for development of drugs in cancer therapy. 4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) has been used in clinic during the past 30 years as an inhibitor of anion transporters and channels. Recently DIDS has been demonstrated to affect Rad51-mediated homologous pairing and strand exchange, key processes in homologous recombination. Consequently, DIDS has been considered as a potential revertant of radio- and chemo-resistance of cancer cells, the major causes of therapy failure. Here, we have investigated the behavior of DIDS towards serum albumins. The effects of environmental factors, primarily, solvent polarity, on DIDS stability were evaluated, and the mechanisms of interaction of DIDS with human or bovine serum albumin were analyzed using isothermal calorimetry, circular dichroism and fluorescence spectroscopies. DIDS interaction with both serum albumins have been demonstrated, and the interaction characteristics have been determined. By comparing these characteristics for several DIDS derivatives, we have identified the DIDS moiety essential for the interaction. Furthermore, site competition data indicate that human albumin has two DIDS-binding sites: a high-affinity site in the IIIA subdomain and a low-affinity one in the IB subdomain. Molecular docking has revealed the key molecular moieties of DIDS responsible for its interactions in each site and shown that the IB site can bind two ligands. These findings show that binding of DIDS to serum albumin may change the balance between the free and bound DIDS forms, thereby affecting its bioavailability and efficacy against Rad51.

We report two members of a French family who are carriers of a rare hemoglobin (Hb) variant leading to erythrocytosis: Hb Saint Nazaire [β103(G5)Phe→Ile

International audience; We describe the clinical, hematologic and genetic characteristics of a retrospective series of 126 subjects from 64 families with hereditary xerocytosis. Twelve patients from six families carried a KCNN4 mutation, five had the recurrent p.Arg352His mutation and one had a new deletion at the exon 7-intron 7 junction. Forty-nine families carried a PIEZO1 mutation, which was a known recurrent mutation in only one-third of the cases and private sequence variation in others; 12 new probably pathogenic missense mutations were identified. The two dominant features leading to diagnosis were hemolysis that persisted after splenectomy and hyperferritinemia, with an inconstant correlation with liver iron content assessed by magnetic resonance imaging. PIEZO1-hereditary xerocytosis was characterized by compensated hemolysis in most cases, perinatal edema of heterogeneous severity in more than 20% of families and a major risk of post-splenectomy thrombotic events, including a high frequency of portal thrombosis. In KCNN4-related disease, the main symptoms were more severe anemia, hemolysis and iron overload, with no clear sign of red cell dehydration; therefore, this disorder would be better described as a ‘Gardos channelopathy’. These data on the largest series to date indicate that PIEZO1-hereditary xerocytosis and Gardos channelopathy are not the same disease although they share hemolysis, a high rate of iron overload and inefficient splenectomy. They demonstrate the high variability in clinical expression as well as genetic bases of PIEZO1-hereditary xerocytosis. These results will help to improve the diagnosis of hereditary xerocytosis and to provide recommendations on the clinical management in terms of splenectomy, iron overload and pregnancy follow-up.

International audience; 4,4-Diisothiocyanostilbene-2,2-disulfonic acid (DIDS) is a well-known ion-exchange inhibitor targeting cardiac functions and indirectly impeding both radio- and chemo-resistance. A joint computational and experimental study is presented to provide deeper insights into DIDS and other members of this family of compounds. To this end, we applied state-of-the-art density functional theory (DFT) and time-dependent DFT methods, in addition to measuring the optical properties. The experimental data show that such compounds are highly sensitive to their environment and that the optical properties change within as little time as 7h. However, the optical properties of DIDS are similar in various acidic/basic environments, which were confirmed by pK(a) computations on both cis and trans isomers. The protonation analysis also highlights that the singly protonated form of DIDS behaves like a proton sponge compound. The experimentally observed redshift that can be seen when going from water to DMSO was reproduced solely by using the solvation model based on density, although the polarization continuum model and implicit/explicit hybrid schemes were also tested. The characteristic broadening of the absorption peak in water and the vibronic fine structure in DMSO were also reproduced thanks to vibronic coupling simulations associated with the solvent reorganization energy. For other stilbene derivatives, a correlation is found between the maximum absorption wavelength and the Hammett parameters.