Search results for "CELLULAR"

Wnt1 is an Lrp5-independent bone-anabolic Wnt ligand.

2018

Wnt signaling is important for proper embryonic development, shaping cell fate and migration, stem cell renewal, and organ and tissue formation. Here, Luther et al. investigated the role of Wnt1 in osteoporosis. Patients with early-onset osteoporosis and with WNT1 mutations had low bone turnover and high fracture rates, and loss of Wnt1 activity caused fracture and osteoporosis in mice. Inducing Wnt1 in bone-forming cells increased bone mass in aged mice, and this process did not require Lrp5, a co-receptor involved in Wnt signaling. This study identifies Wnt1 as an anabolic (bone building) factor and suggests that it might be a therapeutic target for osteoporosis.WNT1 mutations in humans a…

Diacylglycerol lipase alpha in astrocytes is involved in maternal care and affective behaviors.

2021

Genetic deletion of cannabinoid CB1 receptors or diacylglycerol lipase alpha (DAGLa), the main enzyme involved in the synthesis of the endocannabinoid (eCB) 2-arachidonoylglycerol (2-AG), produced profound phenotypes in animal models of depression-related behaviors. Furthermore, clinical studies have shown that antagonists of CB1 can increase the incidence and severity of major depressive episodes. However, the underlying pathomechanisms are largely unknown. In this study, we have focused on the possible involvement of astrocytes. Using the highly sensitive RNAscope technology, we show for the first time that a subpopulation of astrocytes in the adult mouse brain expresses Dagla, albeit at …

Deconvolution of the cellular origin in hepatocellular carcinoma: Hepatocytes take the center stage.

2016

The expression of biliary/progenitor markers by hepatocellular carcinoma (HCC) is often associated with poor prognosis and stem cell-like behaviors of tumor cells. Hepatocellular adenomas (HCA) also often express biliary/progenitor markers and frequently act as precursor lesions for HCC. However, the cell of origin of HCA and HCC that expresses these markers still remains unclear. Therefore, to evaluate if mature hepatocytes give rise to HCA and HCC tumors, and to understand the molecular pathways involved in tumorigenesis, we lineage-labeled hepatocytes by injecting adeno-associated virus (AAV) containing thyroxine-binding globulin (TBG) promoter driven-Cre into RosaYFP mice. Yellow fluore…

Reply to: “Performance status in patients with HCC: New kid on the block”

2017

Hepatocellular carcinoma and direct-acting antivirals: A never ending story?

2017

Systemic treatment of HCC in special populations

2020

Summary Recent years have seen significant progress in the systemic treatment of hepatocellular carcinoma (HCC), including the advent of immunotherapy. While several large phase III trials have provided the evidence for a multi-line treatment paradigm, they have focused on a highly selected group of patients by excluding potentially confounding comorbidities. As a result, high quality evidence for the systemic treatment of HCC in patients with various comorbidities is missing. This review summarises current knowledge on the use of approved medicines in patients with HIV, autoimmune disease, cardiovascular disease, diabetes, fibrolamellar HCC, mixed HCC-cholangiocarcinoma, decompensated cirr…

Short Term Palmitate Supply Impairs Intestinal Insulin Signaling via Ceramide Production

2016

International audience; The worldwide prevalence of metabolic diseases is increasing, and there are global recommendations to limit consumption of certain nutrients, especially saturated lipids. Insulin resistance, a common trait occurring in obesity and type 2 diabetes, is associated with intestinal lipoprotein overproduction. However, the mechanisms by which the intestine develops insulin resistance in response to lipid overload remain unknown. Here, we show that insulin inhibits triglyceride secretion and intestinal microsomal triglyceride transfer protein expression in vivo in healthy mice force-fed monounsaturated fatty acid-rich olive oil but not in mice force-fed saturated fatty acid…

Chronic hyponatremia in a patient with renal salt wasting and without cerebral disease: relationship between RSW, risk of fractures and cognitive imp…

2018

Renal salt wasting syndrome (RSW) is defined as a renal loss of sodium leading to hyponatremia and a decrease in extracellular fluid volume (ECV). Differentiation of this disorder from the syndrome of inappropriate antidiuretic hormone secretion (SIADH), a common cause of hyponatremia, can be difficult because both can present with hyponatremia and concentrated urine with natriuresis. Our clinical case about a 78-year-old woman with a recent fracture of the right femur not only confirms that this syndrome can occur in patients without intracranial pathologies (CT documented), but depicts how the hyponatremia caused by RSW can show a chronic, oscillating course. This is an interesting point …

Hepatic B cell leukemia-3 promotes hepatic steatosis and inflammation through insulin-sensitive metabolic transcription factors.

2016

Background & Aims The pathomechanisms underlying non-alcoholic fatty liver disease (NAFLD) and the involved molecular regulators are incompletely explored. The nuclear factor-kappa B (NF-κB)-cofactor gene B cell leukemia-3 ( Bcl-3 ) plays a critical role in altering the transcriptional capacity of NF-κB – a key inducer of inflammation – but also of genes involved in cellular energy metabolism. Methods To define the role of Bcl-3 in non-alcoholic steatohepatitis (NASH), we developed a novel transgenic mouse model with hepatocyte-specific overexpression of Bcl-3 ( Bcl-3 Hep ) and employed a high-fat, high-carbohydrate dietary feeding model. To characterize the transgenic model, deep RNA seque…

Hepatic benefits of HCV cure

2020

Direct-acting antiviral (DAA)-induced HCV clearance conceivably leads to improved outcomes at all stages of liver disease. However, available data suggest that the maximum measurable benefit is obtained by treating patients before they reach the stage of compensated advanced chronic liver disease (cACLD). Ideally, all patients with chronic hepatitis C should be treated before they develop advanced fibrosis or cirrhosis, since even if sustained virologic response (SVR) reduces the risk of hepatic events (e.g. decompensation and hepatocellular carcinoma [HCC]) and improves survival, further progression of liver disease and adverse outcomes, including hepatic deaths, cannot be entirely avoided…