Carola Otth has research interest on the study of the possible neurodegenerative effects, neuronal dysfunctions and innate immune activation on neurons and astrocytes infected with the neurotropic virus as HSV-1.

It has been described that during viral infection the protein synthesis is highly increased at the endoplasmic reticulum (ER), condition that in some cases trigger ER stress responses by the accumulation of misfolded proteins. Herpes simplex virus type-1 (HSV-1) is a neurotropic virus that causes a latent persistent infection in humans. It has been postulated that during productive infection herpes virus use the ERAD pathway to avoid the immune response; however, the contribution in the viral replication efficiency is unknown. The aim of this study was to investigate the role of the ERAD enhancer EDEM1, an endoplasmic reticulum lectin protein that works in the recognition of misfolded glycoproteins during productive HSV-1 infection. Human neuroglioma cells (H4) stably expressing either luciferase shRNA or EDEM1 shRNA were infected with HSV-1 wild type or mutant null to ICP0 (protein with E3 ubiquitin ligase activity) or US3 (a protein kinase that modifies host cellular machinery). After infection, levels of EDEM1 were measured by either mRNA (RT-PCR) or protein levels (immunoblotting). Our results showed that HSV-1 infection decreases the levels of EDEM1 to favor viral replication efficiency. The relevance of this study is the elucidation of the contribution of the ERAD pathway in the productive infection of HSV-1 and the possible involvement of ICP0 and/or US3 in this pathway.

Henri Alexandre Giblot Ducray was graduated from the St. Ambrose University, Iowa, with a BSc in Biology with a Biomedical Science concentration and is currently pursuing PhD at Auburn University, Alabama, in Anatomy, Physiology and Pharmacology Department. He is a Graduate Research Assistant for Dr. Sorokulova and has been involved in several of her research projects.

The gut barrier integrity plays a crucial role in health, preventing the translocation of the luminal contents into circulation. One in particular is lipopolysaccharides (LPS), a toxic component of Gram-negative bacteria that is a potent stimulator of inflammation. Increased intestinal permeability accompanies different pathological conditions. Heat stress was shown to disrupt the intestinal barrier function and change the expression of tight junction (TJ) proteins, responsible for maintaining the integrity of the gut. The gut barrier integrity is key for intestinal homeostasis and overall for the health status of the host. It was shown that microbiota and its metabolites can regulate the gut barrier function. Prebiotics have been proposed as a promising approach to normalize microbiota and as a result, improve the gut barrier integrity. The main aim of this study was to evaluate the protective effect of a yeast fermentate product EpiCor (EH) on the intestinal barrier integrity during heat stress. Rats were orally treated with the EH prebiotic product (7 mg/kg in 1 mL of PBS) or with PBS for 14 days and exposed to heat stress conditions (45 oC for 25 min). Control rats received the same treatment but were kept at room temperature. Expression of tight junction (TJ) proteins (claudin 1, occludin, ZO-1 and JAM-A) in the intestine were analyzed by Western blot in all rats, a number of Paneth and goblet cells was also calculated in all samples. Pre-treatment with EH prevented the adverse effects of heat: Decrease in the number of Paneth and goblet cells, elevation of LPS in circulation and decrease of TJ proteins expression. Our results demonstrated efficacy of EH treatment in protecting the integrity of the intestinal barrier in the heat stress model. We speculate that EH could be used for improvement of the gut barrier function in certain pathological conditions.

Yessenia Valverde has completed her PhD in 2013 from Niigata University Graduate school of Medical and Dental Sciences, Japan and currently persuing postdoctoral research from University of Illinois at Chicago College of Dentistry. She has exemplary training in rodent model of dental nerve denervation with the BDNF modulation.

The nuclear enzyme poly(ADP-ribose) polymerase (PARP-1) has been implicated its role in several stem cells fate determination and differentiation. The role of PARP-1 in dental pulp stem cell (DPSC) differentiation especially in the context of its ability to modulate nerve regeneration factor has not been ivestigated. Neurotrophins are an essential group of nerve regeneration signals. In this study, we investigated the role of PARP-1 in the modulation of brain-derived neurotrophic factor (BDNF) in DPSCs derived odontoblast-like cells. Human DPSCs were prepared from healthy molars at the 2/3 root formation stage by the explant outgrowth method. DPSCs were cultured in regular media and osteogenic media and treated with PARP-1 antagonist and PARP1 exogeneous protein for 72 hours in regular media (regular growth media), and then swapped with osteogenic media for 21 days. The PARP-1 inhibitor and protein were treated every three days during the whole differentiation process. Immunohistochmistry, PCR and western analysis for the BDNF and various differentiation markers were performed. Our PCR results demonstrate that differentiated cells show odontoblast-like properties as they express odontogenic markers such as DSPP and RUNX. There is possibility that the PARP1 treatment induces DPSCs into other cell types. Some show very unique morphology with large cytoplasm and oval nucleus. PARP-1 inhibition significantly increased BDNF secretion in the diffentiated cells. This observation was confirmed by both immunohistochemistry and western blot. Taken together, our results indicate that PARP-1 constitutes a negative regulator of the BDNF secretion during odontogenic DPSC differentiation demonstrating its potential for successful nerve regeneration engineering strategies.

Amer Marachli is an undergraduate student at the University of Illinois at Urbana-Champaign with a bachelors in science in Molecuar and Cellular Biology. He joined Dr. Seung Chung`s lab as a Summer Research Intern in June 2017, and successfully completed his project regarding the role of C5a in DPSC odontogenic differentiation. He plans to apply to dental schools in the fall of 2017.

Dental pulp stem cells (DPSCs) are multipotent/undifferentiated cells that are found in the soft living tissue within the dental pulp. Given their easy access compared to other stem cells, they have been given much attention in recent regenerative medicine. Odontoblasts are dentin-making cells in the pulp and have a significant role in dentin-pulp repair in injured teeth. Our team demonstrated for the first time that the complement system, a major component of innate immunity and inflammation, is activated at the injured site of human carious teeth and plays an important role in dental nerve regeneration. We extend this observation in DPSC differentiation. The role of complement fragment C5a in the differentiation of DPSCs is unknown. Human DPSCs were prepared from healthy molars at the 2/3 root formation stage by the explant outgrowth method. DPSCs were cultured in regular media and osteogenic media and treated with C5a antagonist and C5a exogeneous protein for 72 hours in regular growth media, and then swapped with osteogenic media for 21 days.The C5a inhibitor and protein were treated every three days during the whole differentiation process. Immunohistochmistry, PCR and western analysis for various differentiation markers were performed. C5a plays a positive role in odontogenic differentiation of DPSCs. The odontogenic differentiation genes, BMP1, ON, RUNX2, DSPP, have all increased relative to the control. Our results demonstrate that C5a constitutes a positive regulator of the odontogenic DPSC differentiation and identified the C5a as a key initial signal to control odontogenic DPSC differentiation.