Allergic asthma is a chronic inflammatory disease characterized by airway inflammation, changes in structural activity, and bronchial hyperactivity. Scientists have tried to mimic such features of human allergic asthma in murine models as the prevalence of asthma in westernized countries has nearly doubled over the last 20 years to an estimated 180,000 asthma-related deaths per year (WHO, 2018). To date there is no cure for asthma; treatment efforts including inhalers, diet intervention and steroidal injection are designed for symptom relief (Roland et al., 2018). Other initiatives include electronic health recording (EHR) allowing patients to co-manage disease in between office visits. Such interventions and therapies are temporary, aiming to minimize severity of symptoms and number of office visits but they do not always alter underlying pathological mechanisms. Thus, suitable efficacy models are needed. The Ovalbumin (OVA) and House Dust Mite (HDM)-induced models are widely-used models to explore underlying pathogenesis of asthma and MD Biosciences is proud to offer both models as resources for testing new therapeutics as well as provide additional ex vivo assessment services to better understand therapeutic method of action.
IL-33 is a member of the IL-1 cytokine family with a widely-recognized inflammatory role in a broad range of skin diseases. It functions as a signaling ligand for the T1/ST2 receptor, also known as IL1RL1, T1 and IL-33R (Palmer and Gabav, 2011). Expression of IL-33 occurs in the nucleus of epithelial and endothelial cells and has been labeled as an “alarmin”—an immunological alarm signaled during cellular distress or cellular necrosis in mammals. Interestingly, recent reports indicate distinct species differences between mice, humans and pigs, prompting further comparative studies. In some murine epidermis models, prominent constitutive IL-33 expression was seen in epidermal keratinocytes and was drastically lost in basal keratinocytes during acute inflammatory events, while other studies observed a drastic increase in IL-33 during inflammatory events (Sundes et al., 2015). The loss of IL-33 from keratinocyte nuclei could be due to protein degradation or another release mechanism not yet identified. In contrast to the prominent constitutive IL-33 expression in murine keratinocytes, IL-33 signal was substantially low in human epidermis, demonstrating weak signals in the nuclei of keratinocytes. The classification as an alarmin is suitable for murine models but may not be as accurate for humans and pigs.
MDB Scientists recently published a paper titled “Human-like cutaneous neuropathologies associated with a porcine model of peripheral neuritis: a translational platform for neuropathic pain”, and has been accepted to appear in the Neurobiology of Pain Journal effective July of 2018.
Neurological diseases often result in a combination of motor and cognitive deficits. Thus, behavioral assessments in conjunction with physiological readouts offer a broader understanding of the basic biological mechanism of disease and cognitive impairment, highly relevant to therapeutic developments. Utilizing rodent and pig models, MD Biosciences offers a variety of behavioral assessment capabilities applicable to (but not limited to) the following subject areas:
Over the past couple of decades, nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) have become the number one cause of liver disease in Western countries. Recent data confirm that NAFLD and NASH play an equally important role in the Middle East, Far East, Africa, the Caribbean, and Latin America. The prevalence of NAFLD/NASH continues to increase along with its associated risk factors, including metabolic disorder, obesity, diabetes and hypertension. Therefore, understanding the mechanism of these diseases has become a priority. Recent investigations into the effect of chronic liver inflammation have shed light on the role of both the adaptive and innate immune systems in both NAFLD and NASH. Long suspected to play a part in such metabolic disorders along with nutrition and hormonal imbalances, the immune system has been of great interest to researchers for development of specific drug targets to maximize glucose regulation, minimize inflammatory damage to tissues and prevent the development of fibrosis that can lead to liver failure.
MDB Gains OECD-GLP certification for In Vivo Glatiramer Acetate Batch Release Testing Services
Batch Release Testing,
Biological Equivalence Assays,
There are many options for preclinical wound healing research. All studies are designed to predict how a particular treatment will behave in a human wound. In vitro studies, particularly those that are performed on human skin equivalent systems can provide relevant data - but what it lacks - is the ability to monitor any pain as a result of the wound and healing. Rodent studies provide an inexpensive method for gaining data, however rodents differ from humans in a number of anatomical and physiological ways. A rodent's hair is dense, the epidermis and dermis is thin, and healing is primarily through contraction.
Cancer: The Metabolic Link
After decades of research into the genetics of cancer, there has been amassing evidence associating these cancer causing genes, or oncogenes, to cellular metabolism and bioenergetics regulation. This metabolic link serves to facilitate the rapid growth and survival that is characteristic of many cancer cells. Given this, it is not surprising that obesity, already known to exacerbate metabolic disorders, is also affiliated with increased cancer risk. As obesity approaches pandemic levels, understanding the mechanisms involved between cancer and organism metabolism becomes increasingly important.
In its 2015 “Year-in-Review”, Science News declared the “Epigenome” has made its “debut”. Why? Because epigenetic alterations; including acetylation, phosphorylation and methylation have been found to be a means by which genes can be regulated post translation.
While not new, numerous clinical studies have recently been published highlighting the important role methylation plays in epigenetic alterations.
Published findings include:
- Mutations in the DNA methyltransferase 3A gene (DNMT3A) in transgenic mice supports clinical findings of clonal dominance occurring in aging populations.
- A poor prognosis in acute myeloid leukemia (AML) is associated with DNMT3A mutations.
- Presence of DNMT3A mutations is associated with poor prognosis in adult T-cell acute lymphoblastic leukemia (T-ALL).
- Hypomethylation (due to loss of the enzymatic activity in the DNMTAs) and Hypermethylation (specifically in the promoter region) have both been observed in malignances.