Open Access Faculty and Graduate Student Articles

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This community provides free, open access to articles written by faculty members and graduate students from schools on the Indianapolis campus, including, but not limited to:

  • Herron School of Art and Design
  • Kelley School of Business
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Browsing Open Access Faculty and Graduate Student Articles by Title

Now showing 1 - 10 of 30386
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    07. The Mechanism of NGF Signaling In Innervation-dependent Corneal Epithelial Renewal: New Topical Treatment For Neurotrophic Keratopathy
    (Wolters Kluwer, 2024-04-19) Hussain, Arif; Mirmoeini, Kaveh; Mulenga, Chilando; Crabtree, Jordan; Tajdaran, Kiana; Henrique, Mario; Blum, Noam; Shalom-Feuerstein, Ruby; Borschel, Gregory; Feinberg, Konstantin; Surgery, School of Medicine
    Background: Corneal clarity is essential for vision. Limbal stem cells (LSCs), the source of transparent corneal epithelial cells, are located in the basal epithelium of the limbus at the corneal-conjunctival interface, where they interact with corneal sensory nerves. Besides protection, corneal nerves may stimulate LSC activity. Pathological corneal denervation can lead to ulcers, scarring, and opacification due to impaired healing from repetitive wounds. This condition, termed Neurotrophic Keratopathy (NK), a major cause of corneal blindness, and lacks a definitive cure. Corneal nerves release various trophic factors that regulate epithelial renewal. Nerve growth factor (NGF) has shown positive effects on corneal healing and maintenance in vivo. Topical recombinant human NGF is the only FDA-approved treatment for NK. However, NGF is not efficacious in 30% of cases, requires very frequent dosing, and costs $100k per course. Moreover, NGF’s ability to heal corneal ulcers is limited. Prior studies showed NGF stimulates proliferation and maintenance of cultured human LSCs, which express TrkA and p75NTR receptors, but didn’t establish a link between NGF signaling and corneal sensory innervation-mediated trophic regulation of epithelial renewal. Furthermore, the role and molecular mechanism of NGF signaling in LSC activity remains unidentified. We hypothesize that NGF, locally expressed in its mature and premature (proNGF) forms, regulates LSC activity-dependent homeostatic and wound-induced corneal epithelial renewal via differential activation of its receptors TrkA and p75NTR, a process dependent on corneal sensory innervation. Methods: A) We conducted in vivo experiments in wild-type and mutant mice and rats to elucidate the NGF signaling mechanism in corneal innervation-dependent epithelial renewal. We examined the effect of combinations of TrkA and p75NTR agonists and antagonists on the healing of experimentally wounded corneas, both intact and surgically denervated. B) To understand the role and mechanism of NGF signaling in LSC activity and its relevance to humans, we assessed the clonogenicity of cultured human LSCs (hLSCs) by pharmacologically modulating NGF receptors, as described in (A). Results: A) While inactivation of TrkA completely prevents healing of normally innervated cornea, inactivation of p75NTR combined with a single daily dose of NGF induces complete and rapid healing of denervated de-epithelialized corneas. B) NGF or specific p75NTR inhibitor THX-B supported colonies’ formation by hLSCs that were further augmented by combination of the two compounds. Conclusions: Corneal sensory nerve-associated expression of NGF in its both forms (NGF and proNGF) regulates the proliferation and differentiation of LSCs by differentially stimulating the activity of the NGF receptors. Combined pharmacological activation and inhibition of TrkA and p75NTR, respectively, will be applied in the development of a superior NGF-based treatment of NK.
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    1,25-Dihydroxyvitamin D3 enhances glucose-stimulated insulin secretion in mouse and human islets: a role for transcriptional regulation of voltage-gated calcium channels by the vitamin D receptor
    (Elsevier, 2018) Kjalarsdottir, Lilja; Tersey, Sarah A.; Vishwanath, Mridula; Chuang, Jen-Chieh; Posner, Bruce A.; Mirmira, Raghavendra G.; Repa, Joyce J.; Pediatrics, School of Medicine
    Aim Vitamin D deficiency in rodents negatively affects glucose-stimulated insulin secretion (GSIS) and human epidemiological studies connect poor vitamin D status with type 2 diabetes. Previous studies performed primarily in rat islets have shown that vitamin D can enhance GSIS. However the molecular pathways linking vitamin D and insulin secretion are currently unknown. Therefore, experiments were undertaken to elucidate the transcriptional role(s) of the vitamin D receptor (VDR) in islet function. Methods Human and mouse islets were cultured with vehicle or 1,25-dihydroxyvitamin-D3 (1,25D3) and then subjected to GSIS assays. Insulin expression, insulin content, glucose uptake and glucose-stimulated calcium influx were tested. Microarray analysis was performed. In silico analysis was used to identify VDR response elements (VDRE) within target genes and their activity was tested using reporter assays. Results Vdr mRNA is abundant in islets and Vdr expression is glucose-responsive. Preincubation of mouse and human islets with 1,25D3 enhances GSIS and increases glucose-stimulated calcium influx. Microarray analysis identified the R-type voltage-gated calcium channel (VGCC) gene, Cacna1e, which is highly upregulated by 1,25D3 in human and mouse islets and contains a conserved VDRE in intron 7. Results from GSIS assays suggest that 1,25D3 might upregulate a variant of R-type VGCC that is resistant to chemical inhibition. Conclusion These results suggest that the role of 1,25D3 in regulating calcium influx acts through the R-Type VGCC during GSIS, thereby modulating the capacity of beta cells to secrete insulin.
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    1- versus 2-Layer Renorrhaphy During Robotic Partial Nephrectomy
    (Society of Laparoscopic & Robotic Surgeons, 2025) Yong, Courtney; Sharfuddin, Asif A.; Sundaram, Chandru P.; Bahler, Clinton D.; Urology, School of Medicine
    Background and objectives: To determine whether 1- versus 2-layer renorrhaphy affects renal function after partial nephrectomy. Methods: A total of 18 patients undergoing robot-assisted partial nephrectomies for renal tumors at a single center were randomized to 1-layer or 2-layer renorrhaphy. All patients received a running base layer for hemostasis and collecting system closure. The 2-layer renorrhaphy group also underwent cortical closure with running suture, sliding clip method. Demographics and surgical outcomes were collected. Three-dimensional renal models were constructed using semiautomatic segmentation and planimetry pre- and 4 months postsurgery to determine renal volume loss. Welch's t test was used with statistical significance defined as P < .05. Results: Of the 18 patients included in the study, 10 were randomized to 1-layer and 8 to 2-layer renorrhaphy. Demographic variables were matched. There was no difference in postoperative creatinine at 1 month (P = .11), 1 year (P = .28), or 3 years (P = .28) postoperatively. However, the change from pre to postoperative creatinine favored the 1-layer group at 1 month (-0.043 vs +0.11 P = .02) and 3 years (-0.0025 vs 0.244, P = .08) follow up. The 1-layer group had a smaller mean volume loss at 4 months postoperatively compared to the 2-layer group (12% vs 22%, P = .04). Conclusion: This small, randomized trial found increased creatinine and volume loss after 2-layer cortical renorrhaphy. Omitting cortical renorrhaphy may result in better preservation of renal volume and function.
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    1-Alpha, 25-dihydroxyvitamin D3 alters the pharmacokinetics of mycophenolic acid in renal transplant recipients by regulating two extrahepatic UDP-glucuronosyltransferases 1A8 and 1A10
    (Elsevier, 2016-12) Wang, Xiaoliang; Wang, Hongwei; Shen, Bing; Overholser, Brian R.; Cooper, Bruce R.; Lu, Yinghao; Tang, Huamei; Zhou, Chongzhi; Sun, Xing; Zhong, Lin; Favus, Murray J.; Decker, Brian S.; Liu, Wanqing; Peng, Zhihai; Department of Medicine, IU School of Medicine
    Mycophenolic acid (MPA) is an important immunosuppressant broadly used in renal transplantation. However, the large inter-patient variability in mycophenolic acid (MPA) pharmacokinetics (PK) limits its use. We hypothesize that extrahepatic metabolism of MPA may have significant impact on MPA PK variability. Two intestinal UDP-glucuronosyltransferases 1A8 and 1A10 plays critical role in MPA metabolism. Both in silico and previous genome-wide analyses suggested that vitamin D (VD) may regulate intestinal UGT1A expression. We validated the VD response elements (VDREs) across the UGT1A locus with chromatin immunoprecipitation (ChIP) and luciferase reporter assays. The impact of 1-alpha,25-dihydroxyvitamin D3 (D3) on UGT1A8 and UGT1A10 transcription and on MPA glucuronidation was tested in human intestinal cell lines LS180, Caco-2 and HCT-116. The correlation between transcription levels of VD receptor (VDR) and the two UGT genes were examined in human normal colorectal tissue samples (n = 73). PK alterations of MPA following the parent drug, mycophenolate mofetil (MMF), and D3 treatment was assessed among renal transplant recipients (n = 10). Our ChIP assay validate three VDREs which were further demonstrated as transcriptional enhancers with the luciferase assays. D3 treatment significantly increased transcription of both UGT genes as well as MPA glucuronidation in cells. The VDR mRNA level was highly correlated with that of both UGT1A8 and UGT1A10 in human colorectal tissue. D3 treatment in patients led to about 40% reduction in both AUC0-12 and Cmax while over 70% elevation of total clearance of MPA. Our study suggested a significant regulatory role of VD on MPA metabolism and PK via modulating extrahepatic UGT activity.
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    10 Great Places to Go for Free Help!
    (Wolters, 2015-01) Meek, Julie A.; School of Nursing
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    10 Tips for Maintaining a Healthy Lifestyle and Body Weight
    (Fairbanks School of Public Health, 2020-03-18) Song, Yiqing; Epidemiology, School of Public Health
    At this extreme moment, we began working from home, away from campus, and keeping social distance for as many people as possible. As we stay home and are stuck with the foods that have been in our fridge or pantry for a while, we are temporarily living a sedentary lifestyle with increased odds of physical inactivity, excessive eating and sitting, stress, anxiety, and depression. In particular, many of us will gain some weight during the pandemic and may keep the extra weight permanently, which may carry considerable health risks for type 2 diabetes, hypertension, heart attack, stroke, and other health problems. Here, I’d like to share some basic tips and resources for how to maintain your healthy lifestyle, body weight, and overall well-being while staying home and engaging in social distancing.
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    100 years of insulin: celebrating the past, present and future of diabetes therapy
    (Springer Nature, 2021) Sims, Emily K.; Carr, Alice L.J.; Oram, Richard A.; DiMeglio, Linda A.; Evans-Molina, Carmella; Pediatrics, School of Medicine
    The year 2021 marks the centennial of Banting and Best's landmark description of the discovery of insulin. This discovery and insulin's rapid clinical deployment effectively transformed type 1 diabetes from a fatal diagnosis into a medically manageable chronic condition. In this Review, we describe key accomplishments leading to and building on this momentous occasion in medical history, including advancements in our understanding of the role of insulin in diabetes pathophysiology, the molecular characterization of insulin and the clinical use of insulin. Achievements are also viewed through the lens of patients impacted by insulin therapy and the evolution of insulin pharmacokinetics and delivery over the past 100 years. Finally, we reflect on the future of insulin therapy and diabetes treatment, as well as challenges to be addressed moving forward, so that the full potential of this transformative discovery may be realized.
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    100% of People Who Confuse Correlation With Causation Eventually Die
    (Sage, 2024-10-03) Schwalb, Jason M.; Neurological Surgery, School of Medicine
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    1021. VP22 Mediates Tumor Vasculature Specific Targeting
    (Elsevier, 2004-05-01) Raikwar, Sudhanshu P.; Gardner, Thomas A.; Kao, Chinghai; Urology, School of Medicine
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