Distinct bile acid alterations in response to a single administration of PFOA and PFDA in mice.

Per- and polyfluoroalkyl substances (PFASs), a group of synthetic chemicals that were once widely used for industrial purposes and in consumer products, are widely found in the environment and in human blood due to their extraordinary resistance to degradation. Once inside the body, PFASs can activate nuclear receptors such as PPARα and CAR. The present study aimed to investigate the impact of perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA) on liver structure and functions, as well as bile acid homeostasis in mice.

IL-22 regulates endometrial regeneration by enhancing tight junctions and orchestrating extracellular matrix.

The uterine endometrium uniquely regenerates after menses, postpartum, or after breaks in the uterine layer integrity throughout women's lives. Direct cell-cell contacts ensured by tight and adherens junctions play an important role in endometrial integrity. Any changes in these junctions can alter the endometrial permeability of the uterus and have an impact on the regeneration of uterine layers.

Regulation of Hox and ParaHox genes by perfluorochemicals in mouse liver.

Homeobox (Hox) genes encode homeodomain proteins, which play important roles in the development and morphological diversification of organisms including plants and animals. Perfluorinated chemicals (PFCs), which are well recognized industrial pollutants and universally detected in human and wildlife, interfere with animal development. In addition, PFCs produce a number of hepatic adverse effects, such as hepatomegaly and dyslipidemia.

Evaluation of Cytotoxicity of Self-Emulsifying Formulations Containing Long-Chain Lipids Using Caco-2 Cell Model: Superior Safety Profile Compared to Medium-Chain Lipids.

Medium-chain (MC) and long-chain (LC) lipids are used for development of self-emulsifying drug delivery systems (SEDDS). MC lipids are often preferred because of their ability to form stable microemulsions with relatively high drug solubilization capacity. On the other hand, LC lipids could be more biocompatible as most endogenous and dietary lipids are LC glycerides.

DNA damage response activates respiration and thereby enlarges dNTP pools to promote cell survival in budding yeast.

The DNA damage response (DDR) is an evolutionarily conserved process essential for cell survival. Previously, we found that decreased histone expression induces mitochondrial respiration, raising the question whether the DDR also stimulates respiration. Here, using oxygen consumption and ATP assays, RT-qPCR and ChIP-qPCR methods, and dNTP analyses, we show that DDR activation in the budding yeast , either by genetic manipulation or by growth in the presence of genotoxic chemicals, induces respiration.

Reciprocal Regulation of AMPK/SNF1 and Protein Acetylation.

Adenosine monophosphate (AMP)-activated protein kinase (AMPK) serves as an energy sensor and master regulator of metabolism. In general, AMPK inhibits anabolism to minimize energy consumption and activates catabolism to increase ATP production. One of the mechanisms employed by AMPK to regulate metabolism is protein acetylation.

Metformin as an Anticancer Agent.

Metformin has been a frontline therapy for type 2 diabetes (T2D) for many years. Its effectiveness in T2D treatment is mostly attributed to its suppression of hepatic gluconeogenesis; however, the mechanistic aspects of metformin action remain elusive. In addition to its glucose-lowering effect, metformin possesses other pleiotropic health-promoting effects that include reduced cancer risk and tumorigenesis.

The proto-oncogene Bcl3 induces immune checkpoint PD-L1 expression, mediating proliferation of ovarian cancer cells.

The proto-oncogene Bcl3 induces survival and proliferation in cancer cells; however, its function and regulation in ovarian cancer (OC) remain unknown. Here, we show that expression is increased in human OC tissues. Surprisingly, however, we found that in addition to promoting survival, proliferation, and migration of OC cells, Bcl3 promotes both constitutive and interferon-γ (IFN)-induced expression of the immune checkpoint molecule PD-L1.

Increased heme synthesis in yeast induces a metabolic switch from fermentation to respiration even under conditions of glucose repression.

Regulation of mitochondrial biogenesis and respiration is a complex process that involves several signaling pathways and transcription factors as well as communication between the nuclear and mitochondrial genomes. Under aerobic conditions, the budding yeast metabolizes glucose predominantly by glycolysis and fermentation. We have recently shown that altered chromatin structure in yeast induces respiration by a mechanism that requires transport and metabolism of pyruvate in mitochondria.

Origin of a rapidly evolving homeostatic control system programming testis function.

Mammals share common strategies for regulating reproduction, including a conserved hypothalamic-pituitary-gonadal axis; yet, individual species exhibit differences in reproductive performance. In this report, we describe the discovery of a species-restricted homeostatic control system programming testis growth and function. is a member of the prolactin gene family and its protein product (PLP-J) was discovered as a uterine cytokine contributing to the establishment of pregnancy.

Epalrestat Stimulated Oxidative Stress, Inflammation, and Fibrogenesis in Mouse Liver.

Epalrestat (EPS), an aldose reductase inhibitor, is widely prescribed to manage diabetic neuropathy. It is generally believed that EPS is beneficial to diabetic patients because it can protect endothelial cells, Schwann cells, or other neural cells from oxidative stress. However, several clinical studies revealed that EPS therapy led to liver dysfunction, which limited its clinical applications.

Histone Deacetylase (HDAC) Inhibition Induces IκB Kinase (IKK)-dependent Interleukin-8/CXCL8 Expression in Ovarian Cancer Cells.

Overexpression of the pro-angiogenic chemokine IL-8 (CXCL8) is associated with a poor prognosis in several solid tumors, including epithelial ovarian cancer (EOC). Even though histone deacetylase (HDAC) inhibition has shown remarkable antitumor activity in hematological malignancies, it has been less effective in solid tumors, including EOC. Here we report results that may explain the decreased efficiency of HDAC inhibition in EOC, based on our data demonstrating that HDAC inhibition specifically induces expression of IL-8/CXCL8 in SKOV3, CAOV3, and OVCAR3 cells.

Berberine-induced Inactivation of Signal Transducer and Activator of Transcription 5 Signaling Promotes Male-specific Expression of a Bile Acid Uptake Transporter.

Sodium-taurocholate co-transporting polypeptide (Ntcp/NTCP) is the major uptake transporter of bile salts in mouse and human livers. In certain diseases, including endotoxemia, cholestasis, diabetes, and hepatocarcinoma, Ntcp/NTCP expression is markedly reduced, which interferes with enterohepatic circulation of bile salts, impairing the absorption of lipophilic compounds. Therefore, normal Ntcp/NTCP expression in the liver is physiologically important.

Activation of GR but not PXR by dexamethasone attenuated acetaminophen hepatotoxicities via Fgf21 induction.

Glucocorticoid receptor (GR) signaling is indispensable for cell growth and development, and plays important roles in drug metabolism. Fibroblast growth factor (Fgf) 21, an important regulator of glucose, lipid, and energy metabolism, plays a cytoprotective role by attenuating toxicities induced by chemicals such as dioxins, acetaminophen (APAP), and alcohols. The present study investigates the impact of dexamethasone (DEX)-activated GR on Fgf21 expression and how it affects the progression of APAP-induced hepatotoxicity.

Assessment of cell viability and permeation enhancement in presence of lipid-based self-emulsifying drug delivery systems using Caco-2 cell model: Polysorbate 80 as the surfactant.

Purpose: Lipid-based self-emulsifying drug delivery systems (SEDDS) are commonly used for solubilizing and enhancing oral bioavailability of poorly water-soluble drugs. However, their effects on viability of intestine epithelial cells and influence on membrane permeation are poorly understood. The present study was undertaken for safety assessment of lipid-based formulations containing medium-chain fatty acid esters as lipids and polysorbate 80 as the surfactant using the Caco-2 in vitro model.

Hormonal and Chemical Regulation of the Glut9 Transporter in Mice.

Glucose transporter (Glut) 9 plays an important role in maintaining the homeostasis of uric acid in the body. Although the physiologic functions of Glut9 have been well established, the regulation of Glut9 expression is less well understood. In this study, we showed that the mRNA and protein expression of Glut9 in mouse liver and kidney are female predominant.

Cytotoxicity assessment of lipid-based self-emulsifying drug delivery system with Caco-2 cell model: Cremophor EL as the surfactant.

Purpose: Caco-2 cells are used extensively for in vitro prediction of intestinal drug absorption. However, toxicity of excipients and formulations used can artificially increase drug permeation by damaging cell monolayers, thus providing misleading results. The present study aimed to investigate cytotoxicity of common lipid-based excipients and formulations on Caco-2 cells.

A Prolactin Family Paralog Regulates Placental Adaptations to a Physiological Stressor.

The prolactin (PRL) family of hormones and cytokines participates in the regulation of optimal reproductive performance in the mouse and rat. Members of the PRL family are expressed in the anterior pituitary, uterus, and/or placenta. In the present study, we investigated the ontogeny of PRL family 7, subfamily b, member 1 (PRL7B1; also called PRL-like protein-N, PLP-N) expression in the developing mouse placenta and established a mouse model for investigating the biological function of PRL7B1.

Neonatal bisphenol A exposure induces meiotic arrest and apoptosis of spermatogenic cells.

Bisphenol A (BPA) is a widely used industrial plasticizer, which is ubiquitously present in the environment and organisms. As an endocrine disruptor, BPA has caused significant concerns regarding its interference with reproductive function. However, little is known about the impact of BPA exposure on early testicular development.

Regulatory pathways controlling the endovascular invasive trophoblast cell lineage.

Hemochorial placentation is characterized by trophoblast-directed uterine spiral artery remodeling. The rat and human both possess hemochorial placentation and exhibit remarkable similarities regarding the depth of trophoblast invasion and the extent of uterine vascular modification. In vitro and in vivo research methodologies have been established using the rat as an animal model to investigate the extravillous/invasive trophoblast lineage.

Subfertility linked to combined luteal insufficiency and uterine progesterone resistance.

Early pregnancy loss is common and can be caused by a range of factors. The Brown Norway (BN) rat exhibits reproductive dysfunction characterized by small litter size and pregnancy failure and represents a model for investigating early pregnancy loss. In this study, we investigated the establishment of pregnancy in the BN rat and gained insight into mechanisms causing its subfertility.

Induction and intracellular localization of Nur77 dictate fenretinide-induced apoptosis of human liver cancer cells.

Fenretinide, a synthetic retinoid, is known to induce apoptosis in various cancer cells. However, the mechanism by which fenretinide induces apoptosis remains unclear. The current study examines the mechanisms of fenretinide-induced apoptosis in human hepatoma cells.

Pregnane X receptor is essential for normal progression of liver regeneration.

Unlabelled: Pregnane X receptor (PXR) mediates xenobiotic and endobiotic metabolism as well as hepatocyte proliferation. To determine the role of PXR in liver regeneration, 2/3 partial hepatectomy (PH) was performed on wild-type and PXR-null mice. Our results showed that hepatic steatosis was markedly suppressed in mice lacking PXR 36 hours after PH, concomitant with reduction of hepatocyte proliferation at the same time point.

Fenretinide-induced apoptosis of Huh-7 hepatocellular carcinoma is retinoic acid receptor beta dependent.

Background: Retinoids are used to treat several types of cancer; however, their effects on liver cancer have not been fully characterized. To investigate the therapeutic potential of retinoids on hepatocellular carcinoma (HCC), the present study evaluates the apoptotic effect of a panel of natural and synthetic retinoids in three human HCC cell lines as well as explores the underlying mechanisms.

Methods: Apoptosis was determined by caspase-3 cleavage using western blot, DNA double-strand breaks using TUNEL assay, and phosphatidylserine translocation using flow cytometry analysis.