The human HIP gene, overexpressed in primary liver cancer encodes for a C-type carbohydrate binding protein with lactose binding activity

AbstractHIP was originally identified as a gene expressed in primary liver cancers, and in normal tissues such as pancreas and small intestine. Based on gene data base homologies, the HIP protein should consist of a signal peptide linked to a single carbohydrate recognition domain. To test this hypothesis HIP and the putative carbohydrate recognition domain encoded by the last 138 C-terminal amino acids, were expressed as glutathione-S -transferase proteins (GST-HIP and GST-HIP-142, respectively). Both recombinant proteins were purified by a single affinity purification step from bacterial lysates and their ability to bind saccharides coupled to trisacryl GF 2000M were tested. Our results show that HIP and HIP-142 proteins bind to lactose, moreover the binding requires divalent cations. Thus the HIP protein is a lactose-binding lectin with the characteristics of a C-type carbohydrate recognition domain of 138 amino acids in the C-terminal region

Regenerating islet-derived protein 3α : A promising therapy for diabetes. Preliminary data in rodents and in humans

Publisher Copyright: © 2022The aim of our study was to test the hypothesis that administration of Regenerating islet-derived protein 3α (Reg3α), a protein described as having protective effects against oxidative stress and anti-inflammatory activity, could participate in the control of glucose homeostasis and potentially be a new target of interest in the treatment of type 2 diabetes. To that end the recombinant human Reg3α protein was administered for one month in insulin-resistant mice fed high fat diet. We performed glucose and insulin tolerance tests, assayed circulating chemokines in plasma and measured glucose uptake in insulin sensitive tissues. We evidenced an increase in insulin sensitivity during an oral glucose tolerance test in ALF-5755 treated mice vs controls and decreased the pro-inflammatory cytokine C-X-C Motif Chemokine Ligand 5 (CXCL5). We also demonstrated an increase in glucose uptake in skeletal muscle. Finally, correlation studies using human and mouse muscle biopsies showed negative correlation between intramuscular Reg3α mRNA expression (or its murine isoform Reg3γ) and insulin resistance. Thus, we have established the proof of concept that Reg3α could be a novel molecule of interest in the treatment of T2D by increasing insulin sensitivity via a skeletal muscle effect.Peer reviewe

Assessment of a six gene panel for the molecular detection of circulating tumor cells in the blood of female cancer patients

<p>Abstract</p> <p>Background</p> <p>The presence of circulating tumor cells (CTC) in the peripheral blood of cancer patients has been described for various solid tumors and their clinical relevance has been shown. CTC detection based on the analysis of epithelial antigens might be hampered by the genetic heterogeneity of the primary tumor and loss of epithelial antigens. Therefore, we aimed to identify new gene markers for the PCR-based detection of CTC in female cancer patients.</p> <p>Methods</p> <p>Gene expression of 38 cancer cell lines (breast, ovarian, cervical and endometrial) and of 10 peripheral blood mononuclear cell (PBMC) samples from healthy female donors was measured using microarray technology (Applied Biosystems). Differentially expressed genes were identified using the maxT test and the 50% one-sided trimmed maxT-test. Confirmatory RT-qPCR was performed for 380 gene targets using the AB TaqMan^®Low Density Arrays. Then, 93 gene targets were analyzed using the same RT-qPCR platform in tumor tissues of 126 patients with primary breast, ovarian or endometrial cancer. Finally, blood samples from 26 healthy women and from 125 patients (primary breast, ovarian, cervical, or endometrial cancer, and advanced breast cancer) were analyzed following OncoQuick enrichment and RNA pre-amplification. Likewise, <it>hMAM </it>and <it>EpCAM </it>gene expression was analyzed in the blood of breast and ovarian cancer patients. For each gene, a cut-off threshold value was set at three standard deviations from the mean expression level of the healthy controls to identify potential markers for CTC detection.</p> <p>Results</p> <p>Six genes were over-expressed in blood samples from 81% of patients with advanced and 29% of patients with primary breast cancer. <it>EpCAM </it>gene expression was detected in 19% and 5% of patients, respectively, whereas <it>hMAM </it>gene expression was observed in the advanced group (39%) only. Multimarker analysis using the new six gene panel positively identified 44% of the cervical, 64% of the endometrial and 19% of the ovarian cancer patients.</p> <p>Conclusions</p> <p>The panel of six genes was found superior to <it>EpCAM </it>and <it>hMAM </it>for the detection of circulating tumor cells in the blood of breast cancer, and they may serve as potential markers for CTC derived from endometrial, cervical, and ovarian cancers.</p

Long COVID: a review and proposed visualization of the complexity of long COVID

Post-Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus – 2 (SARS-CoV-2) infection, or Long COVID, is a prevailing second pandemic with nearly 100 million affected individuals globally and counting. We propose a visual description of the complexity of Long COVID and its pathogenesis that can be used by researchers, clinicians, and public health officials to guide the global effort toward an improved understanding of Long COVID and the eventual mechanism-based provision of care to afflicted patients. The proposed visualization or framework for Long COVID should be an evidence-based, dynamic, modular, and systems-level approach to the condition. Furthermore, with further research such a framework could establish the strength of the relationships between pre-existing conditions (or risk factors), biological mechanisms, and resulting clinical phenotypes and outcomes of Long COVID. Notwithstanding the significant contribution that disparities in access to care and social determinants of health have on outcomes and disease course of long COVID, our model focuses primarily on biological mechanisms. Accordingly, the proposed visualization sets out to guide scientific, clinical, and public health efforts to better understand and abrogate the health burden imposed by long COVID

[Closing Remarks and Prospect]

24 January 2003 closing speech at the Conference "Open Access to Scientific and Technical Information: State of the Art and Future Trends". The textual version was published in "Information Services and Use", vol. 23 (2003), issue 2-3, p. 187-189

Capside du virus de l'hépatite C et métabolisme lipidique hépatique

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Transfert de gène dans le foie (application aux hépatocarcinomes)

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Identification d'un marqueur précoce potentiel et caractérisation du rôle de l'initiation dans le processus cancéreux suite à l'étude des mécanismes moléculaires impliqués dans l'hépatocarcinogénèse non -génotoxique induite par l'acide clorifibrique chez le rat

L'évaluation de l'effet hépatocarcinogène non génotoxique (HNG) d'une molécule en développement nécessite des études longues (2 ans) réalisés chez les rongeurs. Le mécanisme d'action de l'acide clofibrique (CLO) , un HNG chez les rongeurs, passe par l'activation d'un récepteur nucléaire le PPARa. La génomique a été utilisée pour obtenir une cartographie exhaustive des effets épigéniques découlant de cette activation transcriptionnelle. L'objectif de notre travail étant de développer des modèles expérimentaux plus courts, nous avons montré que l'addition d'une étape d'initiation permet d'accélerer l'apparition des lésions néoplasiques induites par le CLO sans modifier le déroulement moléculaire de cancérogénèse. Pour étudier spécifiquement les cellules prénéoplasiques , nous avons évalué la faisabilité de combiner la microdissection laserPARIS5-BU-Necker : Fermée (751152101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF