Mechano-dependent sorbitol accumulation supports biomolecular condensate.

Condensed droplets of protein regulate many cellular functions, yet the physiological conditions regulating their formation remain largely unexplored. Increasing our understanding of these mechanisms is paramount, as failure to control condensate formation and dynamics can lead to many diseases. Here, we provide evidence that matrix stiffening promotes biomolecular condensation in vivo.

Dietary intake and glutamine-serine metabolism control pathologic vascular stiffness.

Perivascular collagen deposition by activated fibroblasts promotes vascular stiffening and drives cardiovascular diseases such as pulmonary hypertension (PH). Whether and how vascular fibroblasts rewire their metabolism to sustain collagen biosynthesis remains unknown. Here, we found that inflammation, hypoxia, and mechanical stress converge on activating the transcriptional coactivators YAP and TAZ (WWTR1) in pulmonary arterial adventitial fibroblasts (PAAFs).

Mechano-dependent sorbitol accumulation supports biomolecular condensate.

Biomolecular condensates regulate a wide range of cellular functions from signaling to RNA metabolism , yet, the physiologic conditions regulating their formation remain largely unexplored. Biomolecular condensate assembly is tightly regulated by the intracellular environment. Changes in the chemical or physical conditions inside cells can stimulate or inhibit condensate formation .

The SH-SY5Y human neuroblastoma cell line, a relevant in vitro cell model for investigating neurotoxicology in human: Focus on organic pollutants.

Investigation of the toxicity triggered by chemicals on the human brain has traditionally relied on approaches using rodent in vivo models and in vitro cell models including primary neuronal cultures and cell lines from rodents. The issues of species differences between humans and rodents, the animal ethical concerns and the time and cost required for neurotoxicity studies on in vivo animal models, do limit the use of animal-based models in neurotoxicology. In this context, human cell models appear relevant in elucidating cellular and molecular impacts of neurotoxicants and facilitating prioritization of in vivo testing.

Hexokinase 2 is a transcriptional target and a positive modulator of AHR signalling.

The aryl hydrocarbon receptor (AHR) regulates the expression of numerous genes in response to activation by agonists including xenobiotics. Although it is well appreciated that environmental signals and cell intrinsic features may modulate this transcriptional response, how it is mechanistically achieved remains poorly understood. We show that hexokinase 2 (HK2) a metabolic enzyme fuelling cancer cell growth, is a transcriptional target of AHR as well as a modulator of its activity.

[Cardiauvergne is a remote monitoring and care coordination service for patients with severe heart failure].

Since 2011, thanks to the cooperation of frontline healthcare professionals, it has provided care to more than 1 200 patients across the Auvergne health region. The organisation, blending telemedicine and human contact, has made this initiative a successful example of how the boundaries between community and hospital healthcare can be removed.

Hydrogel films and coatings by swelling-induced gelation.

Hydrogel films used as membranes or coatings are essential components of devices interfaced with biological systems. Their design is greatly challenged by the need to find mild synthesis and processing conditions that preserve their biocompatibility and the integrity of encapsulated compounds. Here, we report an approach to produce hydrogel films spontaneously in aqueous polymer solutions.

First combined in vivo X-ray tomography and high-resolution molecular electron paramagnetic resonance (EPR) imaging of the mouse knee joint taking into account the disappearance kinetics of the EPR probe.

Although laboratory data clearly suggest a role for oxidants (dioxygen and free radicals derived from dioxygen) in the pathogenesis of many age-related and degenerative diseases (such as arthrosis and arthritis), methods to image such species in vivo are still very limited. This methodological problem limits physiopathologic studies about the role of those species in vivo, the effects of their regulation using various drugs, and the evaluation of their levels for diagnosis of degenerative diseases. In vivo electron paramagnetic resonance (EPR) imaging and spectroscopy are unique, noninvasive methods used to specifically detect and quantify paramagnetic species.

Control of gene expression by the retinoic acid-related orphan receptor alpha in HepG2 human hepatoma cells.

Retinoic acid-related Orphan Receptor alpha (RORα; NR1F1) is a widely distributed nuclear receptor involved in several (patho)physiological functions including lipid metabolism, inflammation, angiogenesis, and circadian rhythm. To better understand the role of this nuclear receptor in liver, we aimed at displaying genes controlled by RORα in liver cells by generating HepG2 human hepatoma cells stably over-expressing RORα. Genes whose expression was altered in these cells versus control cells were displayed using micro-arrays followed by qRT-PCR analysis.

Design of group IIA secreted/synovial phospholipase A(2) inhibitors: an oxadiazolone derivative suppresses chondrocyte prostaglandin E(2) secretion.

Group IIA secreted/synovial phospholipase A(2) (GIIAPLA(2)) is an enzyme involved in the synthesis of eicosanoids such as prostaglandin E(2) (PGE(2)), the main eicosanoid contributing to pain and inflammation in rheumatic diseases. We designed, by molecular modeling, 7 novel analogs of 3-{4-[5(indol-1-yl)pentoxy]benzyl}-4H-1,2,4-oxadiazol-5-one, denoted C1, an inhibitor of the GIIAPLA(2) enzyme. We report the results of molecular dynamics studies of the complexes between these derivatives and GIIAPLA(2), along with their chemical synthesis and results from PLA(2) inhibition tests.

Re-evaluation of the role of STOX1 transcription factor in placental development and preeclampsia.

Preeclampsia is a common disease of pregnancy, characterized by high blood pressure and proteinuria appearing from the second trimester of gestation. Preeclampsia has been shown to have a strong genetic component. In 2005 a positional cloning project led to the discovery of the STOX1 transcription factor, and mutations of this gene were proposed as causal for preeclampsia in Dutch families.

STOX1 overexpression in choriocarcinoma cells mimics transcriptional alterations observed in preeclamptic placentas.

Background: Mutations in STOX1 were proposed to be causal for predisposing to preeclampsia, a hypertensive disorder originating from placental defects, affecting up to 10% of human pregnancies. However, after the first study published in 2005 three other groups have dismissed the polymorphism described in the first paper as a causal mutation.

Methodology And Principal Findings: In the present study, we have produced a choriocarcinoma cell line overexpressing STOX1.

Cytosolic aspartate aminotransferase, a new partner in adipocyte glyceroneogenesis and an atypical target of thiazolidinedione.

We show that cytosolic aspartate aminotransferase (cAspAT) is involved in adipocyte glyceroneogenesis, a regulated pathway that controls fatty acid homeostasis by promoting glycerol 3-phosphate formation for fatty acid re-esterification during fasting. cAspAT activity, as well as the incorporation of [(14)C]aspartate into the neutral lipid fraction of 3T3-F442A adipocytes was stimulated by the thiazolidinedione (TZD) rosiglitazone. Conversely, the ratio of fatty acid to glycerol released into the medium decreased.

The gene encoding fibrinogen-beta is a target for retinoic acid receptor-related orphan receptor alpha.

Fibrinogen is a plasma protein synthesized by the liver. It is composed of three chains (alpha, beta, gamma). In addition to its main function as a coagulation factor, this acute phase protein is also a risk marker for atherosclerosis.

The gene encoding human retinoic acid-receptor-related orphan receptor alpha is a target for hypoxia-inducible factor 1.

Retinoic acid-receptor-related orphan receptor (ROR) alpha is a nuclear receptor involved in many pathophysiological processes such as cerebellar ataxia, inflammation, atherosclerosis and angiogenesis. In the present study we first demonstrate that hypoxia increases the amount of Rora transcripts in a wide panel of cell lines derived from diverse tissues. In addition, we identified a functional promoter sequence upstream of the first exon of the human Rora gene, spanning -487 and -45 from the translation initiation site of RORalpha1.

The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation.

The present study was aimed at determining whether hepcidin, a recently identified peptide involved in iron metabolism, plays a role in conditions associated with both iron overload and iron deficiency. Hepcidin mRNA levels were assessed in two models of anemia, acute hemolysis provoked by phenylhydrazine and bleeding provoked by repeated phlebotomies. Hepcidin response to hypoxia was also studied, both ex vivo, in human hepatoma cells, and in vivo.

Retinoic acid receptor-related orphan receptor (ROR) alpha4 is the predominant isoform of the nuclear receptor RORalpha in the liver and is up-regulated by hypoxia in HepG2 human hepatoma cells.

The retinoic acid receptor-related orphan receptor alpha (RORalpha) is critically involved in many physiological functions in several organs. We find that the main RORalpha isoform in the mouse liver is the RORalpha4 isoform, in terms of both mRNA and protein levels, while the RORalpha1 isoform is less abundant. Because hypoxia is a major feature of liver physiology and pathology, we examined the effect of this stress on Rora gene expression and RORalpha transcriptional activity.

Repression of alpha-fetoprotein gene expression under hypoxic conditions in human hepatoma cells: characterization of a negative hypoxia response element that mediates opposite effects of hypoxia inducible factor-1 and c-Myc.

Hypoxia is an important component of many pathological processes including cancerogenesis and cirrhosis. We have attempted to identify additional hepatic genes sensitive to hypoxia by postulating that genes with possible binding sites for hypoxia inducible factor-1 (HIF-1) are regulated by hypoxia. A computer analysis identified the oncodevelopmental alpha-fetoprotein gene (afp) as one of them.