Identification of Early Stage Liver Fibrosis by Modifications in the Interstitial Space Diffusive Microenvironment Using Fluorescent Single-Walled Carbon Nanotubes.

During liver fibrosis, recurrent hepatic injuries lead to the accumulation of collagen and other extracellular matrix components in the interstitial space, ultimately disrupting liver functions. Early stages of liver fibrosis may be reversible, but opportunities for diagnosis at these stages are currently limited. Here, we show that the alterations of the interstitial space associated with fibrosis can be probed by tracking individual fluorescent single-walled carbon nanotubes (SWCNTs) diffusing in that space.

Extracellular vesicles are carriers of adiponectin with insulin-sensitizing and anti-inflammatory properties.

Recent evidence supporting that adipose tissue (AT)-derived extracellular vesicles (EVs) carry an important part of the AT secretome led us to characterize the EV-adipokine profile. In addition to evidencing a high AT-derived EV secretion ability that is further increased by obesity, we identify enrichment of oligomeric forms of adiponectin in small EVs (sEVs). This adipokine is mainly distributed at the EV external surface as a result of nonspecific adsorption of soluble adiponectin.

The Tyrosine Phosphatase SHP2: A New Target for Insulin Resistance?

The SH2 containing protein tyrosine phosphatase 2(SHP2) plays essential roles in fundamental signaling pathways, conferring on it versatile physiological functions during development and in homeostasis maintenance, and leading to major pathological outcomes when dysregulated. Many studies have documented that SHP2 modulation disrupted glucose homeostasis, pointing out a relationship between its dysfunction and insulin resistance, and the therapeutic potential of its targeting. While studies from cellular or tissue-specific models concluded on both pros-and-cons effects of SHP2 on insulin resistance, recent data from integrated systems argued for an insulin resistance promoting role for SHP2, and therefore a therapeutic benefit of its inhibition.

Nuclear HMGB1 protects from nonalcoholic fatty liver disease through negative regulation of liver X receptor.

Dysregulations of lipid metabolism in the liver may trigger steatosis progression, leading to potentially severe clinical consequences such as nonalcoholic fatty liver diseases (NAFLDs). Molecular mechanisms underlying liver lipogenesis are very complex and fine-tuned by chromatin dynamics and multiple key transcription factors. Here, we demonstrate that the nuclear factor HMGB1 acts as a strong repressor of liver lipogenesis.

SHP2 drives inflammation-triggered insulin resistance by reshaping tissue macrophage populations.

Insulin resistance is a key event in type 2 diabetes onset and a major comorbidity of obesity. It results from a combination of fat excess-triggered defects, including lipotoxicity and metaflammation, but the causal mechanisms remain difficult to identify. Here, we report that hyperactivation of the tyrosine phosphatase SHP2 found in Noonan syndrome (NS) led to an unsuspected insulin resistance profile uncoupled from altered lipid management (for example, obesity or ectopic lipid deposits) in both patients and mice.

Integrative study of diet-induced mouse models of NAFLD identifies PPARα as a sexually dimorphic drug target.

Objective: We evaluated the influence of sex on the pathophysiology of non-alcoholic fatty liver disease (NAFLD). We investigated diet-induced phenotypic responses to define sex-specific regulation between healthy liver and NAFLD to identify influential pathways in different preclinical murine models and their relevance in humans.

Design: Different models of diet-induced NAFLD (high-fat diet, choline-deficient high-fat diet, Western diet or Western diet supplemented with fructose and glucose in drinking water) were compared with a control diet in male and female mice.

Reassessment of the involvement of Snord115 in the serotonin 2c receptor pathway in a genetically relevant mouse model.

has been proposed to promote the activity of serotonin (HTR2C) receptor via its ability to base pair with its pre-mRNA and regulate alternative RNA splicing and/or A-to-I RNA editing. Because genes are deleted in most patients with the Prader-Willi syndrome (PWS), diminished HTR2C receptor activity could contribute to the impaired emotional response and/or compulsive overeating characteristic of this disease. In order to test this appealing but never demonstrated hypothesis in vivo, we created a CRISPR/Cas9-mediated knockout mouse.

Macrophage-derived HMGB1 is dispensable for tissue fibrogenesis.

Alarmins and damage-associated molecular patterns (DAMPs) are powerful inflammatory mediators, capable of initiating and maintaining sterile inflammation during acute or chronic tissue injury. Recent evidence suggests that alarmins/DAMPs may also trigger tissue regeneration and repair, suggesting a potential contribution to tissue fibrogenesis. High mobility group B1 (HMGB1), a bona fide alarmin/DAMP, may be released passively by necrotic cells or actively secreted by innate immune cells.

The Release of Adipose Stromal Cells from Subcutaneous Adipose Tissue Regulates Ectopic Intramuscular Adipocyte Deposition.

Ectopic lipid deposition (ELD) is defined by excess fat storage in locations not classically associated with adipose tissue (AT) storage. ELD is positively correlated with insulin resistance and increased risk of metabolic disorders. ELD appears as lipid droplets or adipocytes, whose cell origin is unknown.

HMGB1 links chronic liver injury to progenitor responses and hepatocarcinogenesis.

Cell death is a key driver of disease progression and carcinogenesis in chronic liver disease (CLD), highlighted by the well-established clinical correlation between hepatocellular death and risk for the development of cirrhosis and hepatocellular carcinoma (HCC). Moreover, hepatocellular death is sufficient to trigger fibrosis and HCC in mice. However, the pathways through which cell death drives CLD progression remain elusive.

Chronic apelin treatment improves hepatic lipid metabolism in obese and insulin-resistant mice by an indirect mechanism.

Purpose: Apelin treatment has been shown to improve insulin sensitivity in insulin resistant mice by acting in skeletal muscles. However, the effects of systemic apelin on the hepatic energy metabolism have not been addressed. We thus aimed to determine the effect of chronic apelin treatment on the hepatic lipid metabolism in insulin resistant mice.

Photo-elicitation with adolescents in qualitative research: an example of its use in exploring family interactions in adolescent psychiatry.

Background: Photo-elicitation is a method used increasingly often in qualitative health research, and its positive effect on the research process is well established today. Photo-elicitation appears to facilitate verbalization and insight and to improve relationships between the researcher and participants, thereby enriching the quality of the data collected. Nonetheless, it is barely used at all in the field of adolescent psychiatry.

Impact of animal health programmes on poverty reduction and sustainable livestock development.

Based on data from publications and field observations, this study analyses the interactions between animal health, rural poverty and the performance and environmental impact of livestock farming in low-income countries and middle-income countries. There are strong statistical correlations between the quality of Veterinary Services, livestock productivity and poverty rates. In countries with effective Veterinary Services, livestock growth stems mainly from productivity gains and poverty rates are the lowest.

Metasynthesis of the Views about Treatment of Anorexia Nervosa in Adolescents: Perspectives of Adolescents, Parents, and Professionals.

Background: Anorexia nervosa in adolescents can be a difficult-to-treat disease. Because qualitative research is a well-established method for deepening our understanding of subjective experiences, such as eating disorders and their treatment, we sought to perform a systematic review of qualitative studies to synthesize the views of adolescents with this disease, their parents, and their healthcare providers about its treatment.

Methods: We performed a thematic synthesis to develop the central themes that summarize all of the topics raised in the articles included in our review.

The lived experience of anorexia nervosa in adolescence, comparison of the points of view of adolescents, parents, and professionals: A metasynthesis.

Background: Anorexia nervosa in adolescence has been increasingly documented in numerous quantitative and qualitative studies. Qualitative research, which focuses on subjective experience, is a well-established method to deepen our understanding and provide new insights about specific diseases.

Objective: We conducted a metasynthesis of qualitative studies to explore how anorexia nervosa is experienced by adolescents, their families, and the health professionals who provide care for them and to compare their perspectives.

Negative regulation of NF-κB p65 activity by serine 536 phosphorylation.

Nuclear factor κB (NF-κB) is a master regulator of inflammation and cell death. Whereas most of the activity of NF-κB is regulated through the inhibitor of κB (IκB) kinase (IKK)-dependent degradation of IκB, IKK also phosphorylates subunits of NF-κB. We investigated the contribution of the phosphorylation of the NF-κB subunit p65 at the IKK phosphorylation site serine 536 (Ser(536)) in humans, which is thought to be required for the activation and nuclear translocation of NF-κB.

Epithelial Transforming Growth Factor-β Signaling Does Not Contribute to Liver Fibrosis but Protects Mice From Cholangiocarcinoma.

Background & Aims: Transforming growth factor-β (TGFβ) exerts key functions in fibrogenic cells, promoting fibrosis development in the liver and other organs. In contrast, the functions of TGFβ in liver epithelial cells are not well understood, despite their high level of responsiveness to TGFβ. We sought to determine the contribution of epithelial TGFβ signaling to hepatic fibrogenesis and carcinogenesis.

Improving animal health and livestock productivity to reduce poverty.

This study is based on scientific publications, statistics and field observations. It shows the importance of livestock in the economy and in the risk management strategies implemented by poor farming households. A comparison of livestock performance trends with the evolution of rural poverty in developing countries indicates that growth in livestock production alone is not enough to reduce rural poverty.

Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential.

The stem cells that maintain and repair the postnatal skeleton remain undefined. One model suggests that perisinusoidal mesenchymal stem cells (MSCs) give rise to osteoblasts, chondrocytes, marrow stromal cells, and adipocytes, although the existence of these cells has not been proven through fate-mapping experiments. We demonstrate here that expression of the bone morphogenetic protein (BMP) antagonist gremlin 1 defines a population of osteochondroreticular (OCR) stem cells in the bone marrow.