Heart disease is the leading cause of death in the developed world and often occurs following myocardial infarction. Apelin is an endogenous prepropeptide that has been studied for its role in improving cardiac contractility and vasodilation but suffers from a short half-life in the body. By encasing apelin in a nanoparticle patch, we were able to slowly release apelin to cardiac tissue and observe its effects for one month following induced myocardial infarction surgery in mice. This study demonstrates that the apelin nanoparticles can protect the heart from myocardial-induced heart failure, observing overall improved cardiac function and reduction of fibrotic scarring associated with post-myocardial infarction compared to a nontreated group.
Platelet Rich Plasma (PRP) is an emerging procedure in regenerative medicine that offers a non-surgical minimally invasive way for tissue repair and regeneration. PRP has many different bioactive molecules that are able to influence and help achieve greater recovery and regenerative outcomes. Diet has many effects on platelets and looking at the mechanism in which platelet function and aggregation are affected with different diets shows how they are able to affect PRP therapy. Looking at these mechanisms allows for better physician recommendations for preprocedural diets to optimize efficacy. This paper conducts a systematic review to investigate the influence that diet can have on PRP outcomes. It was shown that high fat diets lower the efficacy of treatment while the Mediterranean diet helps promote platelet function and help efficacy. The future is to look at more diets while also integrating lifestyle choice before treatment for optimal outcomes.
Maternal morbidity and mortality rates in the United States continues to rise, with a wide range of contributing factors such as mental illness, cardiovascular disease and systemic inequality. This metastudy provides a holistic view of the research that has been published on the issue of U.S. maternal healthcare from 2000-2022. The patterns of publications on specific topics over time can tell us what is perceived as a current major cause by physicians, public leaders, researchers, and the public. A deeper dive into systemic inequality as a cause of maternal morbidity and mortality highlights it as a major contributor to these high rates, but that progress is slowly being made through the implementation of detection and prevention tactics, as well as accessible prenatal programs and care.
damage, immune system activation, impaired protein function, or aberrant DNA methylation. In the case of DNA methylation, I demonstrate that inhibiting DNA methylation dynamics can impair long-term memory formation, while the nurse-to- forager transition is not altered. These experiments could serve as the bases for and reference groups of studies testing the effects of metal or metalloid toxicity on DNA methylation. Each potential mechanism provides an avenue for investigating how neural function is influenced by the physiological status of non-neural organs. And from an ecological perspective, my results highlight the need for environmental policy to consider sublethal effects in determining safe environmental toxin loads for honey bees and other insect pollinators.
treatments, and neo-antigens are the targets of immune system in cancer patients who
respond to the treatments. The cancer vaccine field is focused on using neo-antigens from
unique point mutations of genomic sequence in the cancer patient for making
personalized cancer vaccines. However, we choose a different path to find frameshift
neo-antigens at the mRNA level and develop broadly effective cancer vaccines based on
frameshift antigens.
In this dissertation, I have summarized and characterized all the potential frameshift
antigens from microsatellite regions in human, dog and mouse. A list of frameshift
antigens was validated by PCR in tumor samples and the mutation rate was calculated for
one candidate – SEC62. I develop a method to screen the antibody response against
frameshift antigens in human and dog cancer patients by using frameshift peptide arrays.
Frameshift antigens selected by positive antibody response in cancer patients or by MHC
predictions show protection in different mouse tumor models. A dog version of the
cancer vaccine based on frameshift antigens was developed and tested in a small safety
trial. The results demonstrate that the vaccine is safe and it can induce strong B and T cell
immune responses. Further, I built the human exon junction frameshift database which
includes all possible frameshift antigens from mis-splicing events in exon junctions, and I
develop a method to find potential frameshift antigens from large cancer
immunosignature dataset with these databases. In addition, I test the idea of ‘early cancer
diagnosis, early treatment’ in a transgenic mouse cancer model. The results show that
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early treatment gives significantly better protection than late treatment and the correct
time point for treatment is crucial to give the best clinical benefit. A model for early
treatment is developed with these results.
Frameshift neo-antigens from microsatellite regions and mis-splicing events are
abundant at mRNA level and they are better antigens than neo-antigens from point
mutations in the genomic sequences of cancer patients in terms of high immunogenicity,
low probability to cause autoimmune diseases and low cost to develop a broadly effective
vaccine. This dissertation demonstrates the feasibility of using frameshift antigens for
cancer vaccine development.
The DENV and the Zika (ZIKV) FVs frequently co-circulate and generally cause mild self-liming febrile illnesses. However, a secondary infection with a heterologous DENV serotype may lead to life threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). DHF/DSS have been linked to antibody dependent enhancement of infection (ADE), a phenomenon that occurs when antibodies (Abs) formed against an initial infection with one serotype of DENV cross-reacts but does not neutralize a heterologous DENV serotype in a secondary infection. Furthermore, Abs raised against the ZIKV have been observed to cross-react with the DENV and vice versa, which can potentially cause ADE and lead to severe DENV disease. The ZIKV can be transmitted vertically and has been linked to devastating congenital defects such as microcephaly in newborns. FDA approved treatments do not exist for DENV and ZIKV illnesses. Thus, there is a need for safe and effective treatments for these co-circulating viruses. Here, a tetravalent bispecific antibody (bsAb) targeting the ZIKV and all four serotypes of the DENV was expressed in the Nicotiana benthamiana (N. benthamiana) plant. Functional assays of the DENV/ZIKV bsAb demonstrated binding, neutralization, and a significant reduction in ADE activity against both the DENV and the ZIKV.
A single chain variable fragment (scFv) and a diabody based on an antibody directed against the immune checkpoint inhibitor PD-L1, were also expressed in N. benthamiana leaves. The smaller sizes of the scFv and diabody confers them with the ability to penetrate deeper tissues making them beneficial in diagnostics, imaging, and possibly cancer therapy. The past few decades has seen long strives in recombinant protein production in plants with significant improvements in production, safety, and efficacy. These characteristics make plants an attractive platform for the production of recombinant proteins, biologics, and therapeutics.