Publication

Prostaglandin E2 (PGE2) is an important lipid mediator modulating various aspects of kidney function. PGE2 exerts its effects via four PGE2 receptors, EP1-EP4. The EP3 receptor is expressed in the thick ascending limb (TAL) and the collecting duct, where it is proposed to inhibit cAMP generation and NaCl and water reabsorption. However, EP3 is also expressed in endothelial cells of arteries and arterioles, which also play a role in kidney function.

SARS-CoV-2 infection impacts multiple organ systems, including the central nervous system (CNS). Multiple reports have described a variety of neurological manifestations associated with infection that may contribute to worsening COVID-19. The neuropathology of SARS-CoV-2 is not well understood, necessitating the development of relevant animal models for investigation. Here, we report marked neuropathology but with limited virus in the CNS of two non-human primate models (NHPs) of SARS-CoV-2 infection.

Question To identify the cellular source of TgfB2 in a time course of cholestatic liver disease using Abcb4-KO mice and PSC patients, and to correlate findings to disease stages. Methods Liver samples from PSC liver biopsies and Abcb4-KO mice at the age of 2-, 6-, 8- and 12-months were stained for HE, Sirius Red and Orcein to visualize inflammation and fibrosis. Morphological evaluation was performed using Ishak and Nakanuma scoring systems.

We investigate as yet an unidentified role of NOX1, a non-phagocytic isoform of the superoxide-generating NADPH oxidase, in immune responses using Nox1-knockout mice (Nox1-KO). The transcripts of NOX1 was expressed in lymphoid tissues, including the spleen, thymus, bone marrow, and inguinal lymphoid nodes. When antibody production after ovalbumin (OVA) immunization was examined, no significant differences were observed in serum anti-OVA IgG levels between wild-type mice (WT) and Nox1-KO.

During obesity, the adipokine resistin, like saturated fatty acids, lead to an impairment of glucose homeostasis control by the hypothalamus, a risk factor for type 2 diabetes (T2D). We investigate the involvement of hypothalamic de novo ceramide synthesis in resistin-induced neuronal inflammation and insulin resistance which lead, to glucose intolerance. Using the mHypoA mouse hypothalamic cell line, we analyzed the impact of resistin overexposure on expression levels of enzymes driving ceramide biosynthesis. Intracellular ceramide contents were quantified by lipidomic analysis.

Introduction The control of energy balance involves communication of peripheral hormones with brain regions controlling food intake and energy expenditure such as the arcuate nucleus of the hypothalamus (ARC). Within the ARC, two primary neuronal subpopulations control energy balance: proopiomelanocortin (POMC) neurons, which reduce food intake and increase energy expenditure; and agouti-related protein (AgRP) neurons, which inhibit POMC neurons and conversely increase food intake and suppress energy expenditure.

Preterm birth affects over 15 million pregnancies annually worldwide, and is associated with severe health risks for both mother and child. The leading cause of clinically indicated, non-spontaneous preterm delivery is preeclampsia, which can lead to maternal and fetal morbidity and mortality if not appropriately and promptly managed. At this time, the only “cure” for preeclampsia is delivery of the fetus and associated products of conception, which presents the clinical challenge of weighing the risks versus benefits of delivery if the pregnancy is preterm.

Metastatic medullary thyroid cancer (MTC) is a rare, but often, aggressive thyroid malignancy with a 5-year survival rate of less than 40% and few effective therapeutic options. Adoptive T cell immunotherapy using chimeric antigen receptor (CAR)-modified T cells (CAR Ts) is showing encouraging results in the treatment of cancer, but development is challenged by the availability of suitable target antigens. We identified glial-derived neurotrophic factor (GDNF) family receptor alpha 4 (GFRα4) as a putative antigen target for CAR-based therapy of MTC.

Immune checkpoint inhibitors (ICIs), including anti-PD-1 therapy, have limited efficacy in patients with microsatellite stable (MSS) colorectal cancer (CRC). Interleukin 17A (IL-17A) activity leads to a protumor microenvironment, dependent on its ability to induce the production of inflammatory mediators, mobilize myeloid cells and reshape the tumor environment. In the present study, we aimed to investigate the role of IL-17A in resistance to antitumor immunity and to explore the feasibility of anti-IL-17A combined with anti-PD-1 therapy in MSS CRC murine models.

Metastatic breast cancer is a leading cause of cancer-related death in women worldwide. Infusion of natural killer (NK) cells is an emerging immunotherapy for such malignant tumors, although elimination of the immunosuppressive tumor environment is required to improve its efficacy. The effects of this "metastatic" tumor environment on NK cells, however, remain largely unknown.