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- Status: Published
Description
Herpes simplex virus 2 (HSV-2) is one of the most common sexually transmitted infections (STI), affecting over 267 million women worldwide. HSV-2 causes a chronic, latent infection that increases the risk for acquisition with other STI, including HIV. Currently, there is no vaccine against HSV-2 and novel anti-viral treatments are needed. IL-36γ is a newly characterized cytokine that has been shown to play a role in inflammation and be upregulated in response to microbial infection and tissue damage. We have shown that IL-36γ is expressed in the female reproductive tract (FRT) and is upregulated by HSV-2 infection in vitro and in vivo. IL-36γ in turn induces production of proinflammatory cytokines and chemokines in human vaginal epithelial cells (VEC) that can aid in immune cell recruitment. We hypothesize that IL-36γ is a key regulator of mucosal inflammation in the FRT and functions to limit HSV-2 infection. We have demonstrated that IL-36γ treatment prior to infection protects against HSV-2 replication, disease severity, and promotes survival in a lethal mouse model. Thus, the objective of this study is to understand the mechanisms whereby IL-36γ inhibits HSV-2 replication. To understand the impact of IL-36γ on the HSV-2 lifecycle, we pretreated VEC with IL-36γ and evaluated viral titer during virus attachment and entry, replication, and cell-to-cell spread by plaque assay. Pretreatment with IL-36γ 4h prior to infection did not significantly reduce viral titers in VEC monolayers relative to untreated groups. This suggesting that IL-36γ may play a more significant role in immune cell recruitment during HSV-2 infection. To test this, FRT tissue samples from HSV-2 infected IL-36γ -/- and WT mice were analyzed by histochemistry to characterize immune cell recruitment. No clear pattern was determined for tissue samples in which cell clusters were observed and cell type within recruited clusters was unable to be identified at the current magnification. As these projects continue, the data will aid in elucidating the mechanism and level to which IL-36γ impacts HSV-2 infection in human VEC and FRT models.
ContributorsAlexander, Thessaly E (Author) / Herbst-Kralovetz, Melissa (Thesis director) / Capco, David (Committee member) / Hogue, Ian (Committee member) / School of Human Evolution & Social Change (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Background: Despite a multitude of health initiatives, obesity rates in America have continued to increase yearly, with obese or overweight people making up two-thirds of the population. Due to a lack of significant results from diet and weight-loss medication, new methods of weight-loss are increasingly considered. This paper looks beyond traditional Western treatments for weight loss and will analyze views and treatments for overweight and obesity in traditional Chinese medicine (TCM).
Methods: Three databases were used to search for papers published after 2010 until October 2019 discussing obesity, overweight and TCM. No forms of Chinese medicine were excluded from the search. Studies were excluded if they did not meet the date criteria or if they overlapped with papers found in other databases.
Results: Six of the selected papers covered acupuncture (electro, balance or catgut embedding acupuncture methods) either jointly with other treatments or alone, one exclusively on moxibustion and three studies on three different types of TCM herbal medicine. Each study showed a statistically significant effect on body mass index (BMI) value decrease or total weight loss (TWL). The six acupuncture papers all showed statistical significance at the 95% CI against control groups (sham acupuncture or no acupuncture) and against before-treatment BMI values or TWL values.
Conclusion: Of the treatments reviewed, almost all acupuncture studies were shown to be consistently effective in treating overweight or obese individuals within this selection of studies, as well as in another meta-analysis. This may be due to acupuncture’s ties to a neuroendocrine mechanism. Future studies should further explore the neuroendocrine connection between acupuncture and weight loss. Herbal medication was also shown to have a significant effect in reducing weight in each study; however, two studies used mice or rats as subjects, therefore understanding the effects on human subjects is limited.
Methods: Three databases were used to search for papers published after 2010 until October 2019 discussing obesity, overweight and TCM. No forms of Chinese medicine were excluded from the search. Studies were excluded if they did not meet the date criteria or if they overlapped with papers found in other databases.
Results: Six of the selected papers covered acupuncture (electro, balance or catgut embedding acupuncture methods) either jointly with other treatments or alone, one exclusively on moxibustion and three studies on three different types of TCM herbal medicine. Each study showed a statistically significant effect on body mass index (BMI) value decrease or total weight loss (TWL). The six acupuncture papers all showed statistical significance at the 95% CI against control groups (sham acupuncture or no acupuncture) and against before-treatment BMI values or TWL values.
Conclusion: Of the treatments reviewed, almost all acupuncture studies were shown to be consistently effective in treating overweight or obese individuals within this selection of studies, as well as in another meta-analysis. This may be due to acupuncture’s ties to a neuroendocrine mechanism. Future studies should further explore the neuroendocrine connection between acupuncture and weight loss. Herbal medication was also shown to have a significant effect in reducing weight in each study; however, two studies used mice or rats as subjects, therefore understanding the effects on human subjects is limited.
ContributorsTung, Kiram Yeo (Author) / Lateef, Dalya (Thesis director) / Capco, David (Committee member) / School of International Letters and Cultures (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Recent studies indicate the presence of nano-scale titanium dioxide (TiO[subscript 2]) as an additive in human foodstuffs, but a practical protocol to isolate and separate nano-fractions from soluble foodstuffs as a source of material remains elusive. As such, we developed a method for separating the nano and submicron fractions found in commercial-grade TiO[subscript 2] (E171) and E171 extracted from soluble foodstuffs and pharmaceutical products (e.g., chewing gum, pain reliever, and allergy medicine). Primary particle analysis of commercial-grade E171 indicated that 54% of particles were nano-sized (i.e., < 100 nm). Isolation and primary particle analysis of five consumer goods intended to be ingested revealed differences in the percent of nano-sized particles from 32%‒58%. Separation and enrichment of nano- and submicron-sized particles from commercial-grade E171 and E171 isolated from foodstuffs and pharmaceuticals was accomplished using rate-zonal centrifugation. Commercial-grade E171 was separated into nano- and submicron-enriched fractions consisting of a nano:submicron fraction of approximately 0.45:1 and 3.2:1, respectively. E171 extracted from gum had nano:submicron fractions of 1.4:1 and 0.19:1 for nano- and submicron-enriched, respectively. We show a difference in particle adhesion to the cell surface, which was found to be dependent on particle size and epithelial orientation. Finally, we provide evidence that E171 particles are not immediately cytotoxic to the Caco-2 human intestinal epithelium model. These data suggest that this separation method is appropriate for studies interested in isolating the nano-sized particle fraction taken directly from consumer products, in order to study separately the effects of nano and submicron particles.
ContributorsFaust, James (Author) / Doudrick, Kyle (Author) / Yang, Yu (Author) / Capco, David (Author) / Westerhoff, Paul (Author) / College of Liberal Arts and Sciences (Contributor) / Molecular and Cellular Biology (Contributor) / School of Life Sciences (Contributor) / Ira A. Fulton Schools of Engineering (Contributor) / School of Sustainable Engineering and the Built Environment (Contributor)
Created2016-10-31
Description
Thousands of mothers are at risk of transmitting mitochondrial diseases to their offspring each year, with the most severe form of these diseases being fatal [1]. With no cure, transmission prevention is the only current hope for decreasing the disease incidence. Current methods of prevention rely on low mutant maternal mitochondrial DNA levels, while those with levels close to or above threshold (>60%) are still at a very high risk of transmission [2]. Two novel approaches may offer hope for preventing and treating mitochondrial disease: mitochondrial replacement therapy, and CRISPR/Cas9. Mitochondrial replacement therapy has emerged as a promising tool that has the potential to prevent transmission in patients with higher mutant mitochondrial loads. This method is the subject of many ethical concerns due its use of a donor embryo to transplant the patient’s nuclear DNA; however, it has ultimately been approved for use in the United Kingdom and was recently declared ethically permissible by the FDA. The leading-edge CRISPR/Cas9 technology exploits the principles of bacterial immune function to target and remove specific sequences of mutated DNA. This may have potential in treating individuals with disease caused by mutant mitochondrial DNA. As the technology progresses, it is important that the ethical considerations herein emerge and become more established. The purpose of this review is to discuss current research surrounding the procedure and efficacy of the techniques, compare the ethical concerns of each approach, and look into the future of mitochondrial gene replacement therapy.
ContributorsFogelman, Sarah (Author) / Santana, Casey (Author) / Bishop, Casey (Author) / Miller, Alyssa (Author) / Capco, David (Author) / College of Liberal Arts and Sciences (Contributor)
Created2016-08-30