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Articles 1 - 30 of 67
Full-Text Articles in Medicine and Health Sciences
Early Renal Denervation Attenuates Cardiac Dysfunction In Heart Failure With Preserved Ejection Fraction, Jake E. Doiron, Zhen Li, Xiaoman Yu, Kyle B. Lapenna, Heather Quiriarte, Timothy D. Allerton, Kashyap Koul, Andrew Malek, Sanjiv J. Shah, Thomas E. Sharp, Traci T. Goodchild, Daniel R. Kapusta, David J. Lefer
Early Renal Denervation Attenuates Cardiac Dysfunction In Heart Failure With Preserved Ejection Fraction, Jake E. Doiron, Zhen Li, Xiaoman Yu, Kyle B. Lapenna, Heather Quiriarte, Timothy D. Allerton, Kashyap Koul, Andrew Malek, Sanjiv J. Shah, Thomas E. Sharp, Traci T. Goodchild, Daniel R. Kapusta, David J. Lefer
School of Graduate Studies Faculty Publications
BACKGROUND: The renal sympathetic nervous system modulates systemic blood pressure, cardiac performance, and renal function. Pathological increases in renal sympathetic nerve activity contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). We investigated the effects of renal sympathetic denervation performed at early or late stages of HFpEF progression. METHODS AND RESULTS: Male ZSF1 obese rats were subjected to radiofrequency renal denervation (RF-RDN) or sham procedure at either 8 weeks or 20 weeks of age and assessed for cardiovascular function, exercise capacity, and cardiorenal fibrosis. Renal norepinephrine and renal nerve tyrosine hydroxylase staining were performed to quantify denervation …
Microbial Interactions Among Gardnerella, Prevotella And Fannyhessea Prior To Incident Bacterial Vaginosis: Protocol For A Prospective, Observational Study, Christina A. Muzny, Jacob H. Elnaggar, Lúcia G.V. Sousa, Ângela Lima, Kristal J. Aaron, Isaac C. Eastlund, Keonte J. Graves, Chaoling Dong, Olivia T. Van Gerwen, Meng Luo, Ashutosh Tamhane, Dustin Long, Nuno Cerca, Christopher M. Taylor
Microbial Interactions Among Gardnerella, Prevotella And Fannyhessea Prior To Incident Bacterial Vaginosis: Protocol For A Prospective, Observational Study, Christina A. Muzny, Jacob H. Elnaggar, Lúcia G.V. Sousa, Ângela Lima, Kristal J. Aaron, Isaac C. Eastlund, Keonte J. Graves, Chaoling Dong, Olivia T. Van Gerwen, Meng Luo, Ashutosh Tamhane, Dustin Long, Nuno Cerca, Christopher M. Taylor
School of Graduate Studies Faculty Publications
Introduction The aetiology of bacterial vaginosis (BV), a biofilm-associated vaginal infection, remains unknown. Epidemiologic data suggest that it is sexually transmitted. BV is characterised by loss of lactic acid-producing lactobacilli and an increase in facultative and strict anaerobic bacteria. Gardnerella spp are present in 95%–100% of cases; Gardnerella vaginalis has been found to be more virulent than other BV-associated bacteria (BVAB) in vitro. However, G. vaginalis is found in women with normal vaginal microbiota and colonisation is not sufficient for BV development. We hypothesise that Gardnerella spp initiate BV biofilm formation, but incident BV (iBV) requires incorporation of other key …
Lung Cancer In Ever- And Never-Smokers: Findings From Multi-Population Gwas Studies, Yafang Li, Xiangjun Xiao, Jianrong Li, Younghun Han, Chao Cheng, Gail F. Fernandes, Shannon E. Slewitzke, Susan M. Rosenberg, Meng Zhu, Jinyoung Byun, Yohan Bossé, James D. Mckay, Demetrios Albanes, Stephan Lam, Adonina Tardon, Chu Chen, Stig E. Bojesen, Maria T. Landi, Mattias Johansson, Angela Risch, Heike Bickeböller, H-Erich Wichmann, David C. Christiani, Gad Rennert, Susanne M. Arnold, Gary E. Goodman, John K. Field, Diptasri Mandal, Et Al
Lung Cancer In Ever- And Never-Smokers: Findings From Multi-Population Gwas Studies, Yafang Li, Xiangjun Xiao, Jianrong Li, Younghun Han, Chao Cheng, Gail F. Fernandes, Shannon E. Slewitzke, Susan M. Rosenberg, Meng Zhu, Jinyoung Byun, Yohan Bossé, James D. Mckay, Demetrios Albanes, Stephan Lam, Adonina Tardon, Chu Chen, Stig E. Bojesen, Maria T. Landi, Mattias Johansson, Angela Risch, Heike Bickeböller, H-Erich Wichmann, David C. Christiani, Gad Rennert, Susanne M. Arnold, Gary E. Goodman, John K. Field, Diptasri Mandal, Et Al
School of Graduate Studies Faculty Publications
BACKGROUND: Clinical, molecular, and genetic epidemiology studies displayed remarkable differences between ever- and never-smoking lung cancer. METHODS: We conducted a stratified multi-population (European, East Asian, and African descent) association study on 44,823 ever-smokers and 20,074 never-smokers to identify novel variants that were missed in the non-stratified analysis. Functional analysis including eQTL colocalization and DNA damage assays, and annotation studies were conducted to evaluate the functional roles of the variants. We further evaluated the impact of smoking quantity on lung cancer risk for the variants associated with ever-smoking lung cancer. RESULTS: Five novel independent loci, GABRA4, inter-genic region 12q24.33, LRRC4C, LINC01088, …
Validating Osteological Correlates For The Hepatic Piston In The American Alligator (Alligator Mississippiensis), Clinton A. Grand Pre, William Thielicke, Raul E. Diaz, Brandon P. Hedrick, Ruth M. Elsey, Emma R. Schachner
Validating Osteological Correlates For The Hepatic Piston In The American Alligator (Alligator Mississippiensis), Clinton A. Grand Pre, William Thielicke, Raul E. Diaz, Brandon P. Hedrick, Ruth M. Elsey, Emma R. Schachner
School of Graduate Studies Faculty Publications
Unlike the majority of sauropsids, which breathe primarily through costal and abdominal muscle contractions, extant crocodilians have evolved the hepatic piston pump, a unique additional ventilatory mechanism powered by the diaphragmaticus muscle. This muscle originates from the bony pelvis, wrapping around the abdominal viscera, extending cranially to the liver. The liver then attaches to the caudal margin of the lungs, resulting in a sub-fusiform morphology for the entire ‘‘pulmo-hepatic-diaphragmatic’’ structure. When the diaphragmaticus muscle contracts during inspiration, the liver is pulled caudally, lowering pressure in the thoracolumbar cavity, and inflating the lungs. It has been established that the hepatic piston …
Editorial; Biophysics Approaches To Investigate Multi-Organ Alcohol-Induced Damage, Janos Paloczi, Youngchan Kim
Editorial; Biophysics Approaches To Investigate Multi-Organ Alcohol-Induced Damage, Janos Paloczi, Youngchan Kim
School of Graduate Studies Faculty Publications
No abstract provided.
Elovanoid-N34 Modulates Txnrd1 Key In Protection Against Oxidative Stress-Related Diseases, Jorgelina M. Calandria, Surjyadipta Bhattacharjee, Sayantani Kala-Bhattacharjee, Pranab K. Mukherjee, Yuehan Feng, Jakob Vowinckel, Tobias Treiber, Nicolas G. Bazan
Elovanoid-N34 Modulates Txnrd1 Key In Protection Against Oxidative Stress-Related Diseases, Jorgelina M. Calandria, Surjyadipta Bhattacharjee, Sayantani Kala-Bhattacharjee, Pranab K. Mukherjee, Yuehan Feng, Jakob Vowinckel, Tobias Treiber, Nicolas G. Bazan
School of Graduate Studies Faculty Publications
The thioredoxin (TXN) system is an NADPH + H+/FAD redox-triggered effector that sustains homeostasis, bioenergetics, detoxifying drug networks, and cell survival in oxidative stress-related diseases. Elovanoid (ELV)-N34 is an endogenously formed lipid mediator in neural cells from omega-3 fatty acid precursors that modulate neuroinflammation and senescence gene programming when reduction-oxidation (redox) homeostasis is disrupted, enhancing cell survival. Limited proteolysis (LiP) screening of human retinal pigment epithelial (RPE) cells identified TXNRD1 isoforms 2, 3, or 5, the reductase of the TXN system, as an intracellular target of ELV-N34. TXNRD1 silencing confirmed that the ELV-N34 target was isoform 2 or 3. This …
Association Of Chlamydia Trachomatis Burden With The Vaginal Microbiota, Bacterial Vaginosis, And Metronidazole Treatment, Caleb M. Ardizzone, Christopher M. Taylor, Evelyn Toh, Rebecca A. Lillis, Jacob H. Elnaggar, John W. Lammons, Patricia Dehon Mott, Emily L. Duffy, Li Shen, Alison J. Quayle
Association Of Chlamydia Trachomatis Burden With The Vaginal Microbiota, Bacterial Vaginosis, And Metronidazole Treatment, Caleb M. Ardizzone, Christopher M. Taylor, Evelyn Toh, Rebecca A. Lillis, Jacob H. Elnaggar, John W. Lammons, Patricia Dehon Mott, Emily L. Duffy, Li Shen, Alison J. Quayle
School of Graduate Studies Faculty Publications
Bacterial vaginosis (BV), a dysbiosis of the vaginal microbiota, is a common coinfection with Chlamydia trachomatis (Ct), and BV-associated bacteria (BVAB) and their products have been implicated in aiding Ct evade natural immunity. Here, we determined if a non-optimal vaginal microbiota was associated with a higher genital Ct burden and if metronidazole, a standard treatment for BV, would reduce Ct burden or aid in natural clearance of Ct infection. Cervicovaginal samples were collected from women at enrollment and, if testing positive for Ct infection, at a follow-up visit approximately one week later. Cervical Ct burden was assessed by inclusion forming …
Abstinence Restores Cardiac Function In Mice With Established Alcohol-Induced Cardiomyopathy, Joshua M. Edavettal, Nicholas R. Harris, Sarah E. Cohen, Janos Paloczi, Bysani Chandrasekar, Jason D. Gardner
Abstinence Restores Cardiac Function In Mice With Established Alcohol-Induced Cardiomyopathy, Joshua M. Edavettal, Nicholas R. Harris, Sarah E. Cohen, Janos Paloczi, Bysani Chandrasekar, Jason D. Gardner
School of Graduate Studies Faculty Publications
Alcohol-induced cardiomyopathy (ACM) has a poor prognosis with up to a 50% chance of death within four years of diagnosis. There are limited studies investigating the potential of abstinence for promoting repair after alcohol-induced cardiac damage, particularly in a controlled preclinical study design. Here, we developed an exposure protocol that led to significant decreases in cardiac function in C57BL6/J mice within 30 days; dP/dt max decreased in the mice fed alcohol for 30 days (8054 ± 664.5 mmHg/s compared to control mice: 11,188 ± 724.2 mmHg/s, p < 0.01), and the dP/dt min decreased, as well (−7711 ± 561 mmHg/s compared to control mice: −10,147 ± 448.2 mmHg/s, p < 0.01). Quantitative PCR was used to investigate inflammatory and fibrotic biomarkers, while histology was used to depict overt changes in cardiac fibrosis. We observed a complete recovery of function after abstinence (dP/dt max increased from 8054 ± 664 mmHg/s at 30 days to 11,967 ± 449 mmHg/s after abstinence, p < 0.01); further, both inflammatory and fibrotic biomarkers decreased after abstinence. These results lay the groundwork for future investigation of the molecular mechanisms underlying recovery from alcohol-induced damage in the heart.
Sutterella And Its Metabolic Pathways Positively Correlate With Vaccine-Elicited Antibody Responses In Infant Rhesus Macaques, Danting Jiang, Ria Goswami, Maria Dennis, Holly Heimsath, Pamela A. Kozlowski, Amir Ardeshir, Koen K.A. Van Rompay, Kristina De Paris, Sallie R. Permar, Neeraj K. Surana
Sutterella And Its Metabolic Pathways Positively Correlate With Vaccine-Elicited Antibody Responses In Infant Rhesus Macaques, Danting Jiang, Ria Goswami, Maria Dennis, Holly Heimsath, Pamela A. Kozlowski, Amir Ardeshir, Koen K.A. Van Rompay, Kristina De Paris, Sallie R. Permar, Neeraj K. Surana
School of Graduate Studies Faculty Publications
Introduction: It is becoming clearer that the microbiota helps drive responses to vaccines; however, little is known about the underlying mechanism. In this study, we aimed to identify microbial features that are associated with vaccine immunogenicity in infant rhesus macaques. Methods: We analyzed 16S rRNA gene sequencing data of 215 fecal samples collected at multiple timepoints from 64 nursery-reared infant macaques that received various HIV vaccine regimens. PERMANOVA tests were performed to determine factors affecting composition of the gut microbiota throughout the first eight months of life in these monkeys. We used DESeq2 to identify differentially abundant bacterial taxa, PICRUSt2 …
Loss Of Cftr Function In Macrophages Alters The Cell Transcriptional Program And Delays Lung Resolution Of Inflammation, Dianne Wellems, Yawen Hu, Scott Jennings, Guoshun Wang
Loss Of Cftr Function In Macrophages Alters The Cell Transcriptional Program And Delays Lung Resolution Of Inflammation, Dianne Wellems, Yawen Hu, Scott Jennings, Guoshun Wang
School of Graduate Studies Faculty Publications
Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by mutations in the CF Transmembrane-conductance Regulator (CFTR) gene. The most severe pathologies of CF occur in the lung, manifesting as chronic bacterial infection, persistent neutrophilic inflammation, and mucopurulent airway obstruction. Despite increasing knowledge of the CF primary defect and the resulting clinical sequelae, the relationship between the CFTR loss of function and the neutrophilic inflammation remains incompletely understood. Here, we report that loss of CFTR function in macrophages causes extended lung inflammation. After intratracheal inoculation with Pseudomonas aeruginosa, mice with a macrophage-specific Cftr-knockout (Mac-CF) were able to mount an …
Dynamics Of Serum-Neutralizing Antibody Responses In Vaccinees Through Multiple Doses Of The Bnt162b2 Vaccine, Jared Sheehan, Caleb M. Ardizzone, Mayank Khanna, Amber J. Trauth, Michael E. Hagensee, Alistair J. Ramsay
Dynamics Of Serum-Neutralizing Antibody Responses In Vaccinees Through Multiple Doses Of The Bnt162b2 Vaccine, Jared Sheehan, Caleb M. Ardizzone, Mayank Khanna, Amber J. Trauth, Michael E. Hagensee, Alistair J. Ramsay
School of Graduate Studies Faculty Publications
SARS-CoV-2 mRNA vaccines are administered as effective prophylactic measures for reducing virus transmission rates and disease severity. To enhance the durability of post-vaccination immunity and combat SARS-CoV-2 variants, boosters have been administered to two-dose vaccinees. However, long-term humoral responses following booster vaccination are not well characterized. A 16-member cohort of healthy SARS-CoV-2 naïve participants were enrolled in this study during a three-dose BNT162b2 vaccine series. Serum samples were collected from vaccinees over 420 days and screened for antigen (Ag)-specific antibody titers, IgG subclass distribution, and neutralizing antibody (nAb) responses. Vaccine boosting restored peak Ag-specific titers with sustained α-RBD IgG and …
Prefrontal Cortex Glutamatergic Adaptations In A Mouse Model Of Alcohol Use Disorder, Mahum T. Siddiqi, Dhruba Podder, Amanda R. Pahng, Alexandria C. Athanason, Tali Nadav, Chelsea Cates-Gatto, Max Kreifeldt, Candice Contet, Amanda J. Roberts, Scott Edwards, Marisa Roberto, Florence P. Varodayan
Prefrontal Cortex Glutamatergic Adaptations In A Mouse Model Of Alcohol Use Disorder, Mahum T. Siddiqi, Dhruba Podder, Amanda R. Pahng, Alexandria C. Athanason, Tali Nadav, Chelsea Cates-Gatto, Max Kreifeldt, Candice Contet, Amanda J. Roberts, Scott Edwards, Marisa Roberto, Florence P. Varodayan
School of Graduate Studies Faculty Publications
Alcohol use disorder (AUD) produces cognitive deficits, indicating a shift in prefrontal cortex (PFC) function. PFC glutamate neurotransmission is mostly mediated by α-amino-3‑hydroxy-5-methyl-4-isoxazolepropionic acid-type ionotropic receptors (AMPARs); however preclinical studies have mostly focused on other receptor subtypes. Here we examined the impact of early withdrawal from chronic ethanol on AMPAR function in the mouse medial PFC (mPFC). Dependent male C57BL/6J mice were generated using the chronic intermittent ethanol vapor-two bottle choice (CIE-2BC) paradigm. Non-dependent mice had access to water and ethanol bottles but did not receive ethanol vapor. Naïve mice had no ethanol exposure. We used patch-clamp electrophysiology to measure …
In Vivo Treatment With Insulin-Like Growth Factor 1 Reduces Ccr5 Expression On Vaccine-Induced Activated Cd4+ T-Cells, Massimiliano Bissa, Veronica Galli, Luca Schifanella, Monica Vaccari, Mohammad Arif Rahman, Giacomo Gorini, Nicolò Binello, Sarkis Sarkis, Anna Gutowska, Isabela Silva De Castro, Melvin N. Doster, Ramona Moles, Guido Ferrari, Xiaoying Shen, Georgia D. Tomaras, David C. Montefiori, Kombo F. N’Guessan, Dominic Paquin-Proulx, Pamela A. Kozlowski, David J. Venzon, Hyoyoung Choo-Wosoba, Matthew W. Breed, Joshua Kramer, Genoveffa Franchini
In Vivo Treatment With Insulin-Like Growth Factor 1 Reduces Ccr5 Expression On Vaccine-Induced Activated Cd4+ T-Cells, Massimiliano Bissa, Veronica Galli, Luca Schifanella, Monica Vaccari, Mohammad Arif Rahman, Giacomo Gorini, Nicolò Binello, Sarkis Sarkis, Anna Gutowska, Isabela Silva De Castro, Melvin N. Doster, Ramona Moles, Guido Ferrari, Xiaoying Shen, Georgia D. Tomaras, David C. Montefiori, Kombo F. N’Guessan, Dominic Paquin-Proulx, Pamela A. Kozlowski, David J. Venzon, Hyoyoung Choo-Wosoba, Matthew W. Breed, Joshua Kramer, Genoveffa Franchini
School of Graduate Studies Faculty Publications
At the heart of the DNA/ALVAC/gp120/alum vaccine’s efficacy in the absence of neutralizing antibodies is a delicate balance of pro- and anti-inflammatory immune responses that effectively decreases the risk of SIVmac251 acquisition in macaques. Vaccine efficacy is linked to antibodies recognizing the V2 helical conformation, DC-10 tolerogenic dendritic cells eliciting the clearance of apoptotic cells via efferocytosis, and CCR5 downregulation on vaccine-induced gut homing CD4+ cells. RAS activation is also linked to vaccine efficacy, which prompted the testing of IGF-1, a potent inducer of RAS activation with vaccination. We found that IGF-1 changed the hierarchy of V1/V2 epitope recognition and …
Integrated Inflammatory Signaling Landscape Response After Delivering Elovanoid Free-Fatty-Acid Precursors Leading To Experimental Stroke Neuroprotection, Madigan M. Reid, Ludmila Belayev, Larissa Khoutorova, Pranab K. Mukherjee, Andre Obenaus, Kierany Shelvin, Stacey Knowles, Sung Ha Hong, Nicolas G. Bazan
Integrated Inflammatory Signaling Landscape Response After Delivering Elovanoid Free-Fatty-Acid Precursors Leading To Experimental Stroke Neuroprotection, Madigan M. Reid, Ludmila Belayev, Larissa Khoutorova, Pranab K. Mukherjee, Andre Obenaus, Kierany Shelvin, Stacey Knowles, Sung Ha Hong, Nicolas G. Bazan
School of Graduate Studies Faculty Publications
Despite efforts to identify modulatory neuroprotective mechanisms of damaging ischemic stroke cascade signaling, a void remains on an effective potential therapeutic. The present study defines neuroprotection by very long-chain polyunsaturated fatty acid (VLC-PUFA) Elovanoid (ELV) precursors C-32:6 and C-34:6 delivered intranasally following experimental ischemic stroke. We demonstrate that these precursors improved neurological deficit, decreased T2WI lesion volume, and increased SMI-71 positive blood vessels and NeuN positive neurons, indicating blood–brain barrier (BBB) protection and neurogenesis modulated by the free fatty acids (FFAs) C-32:6 and C-34:6. Gene expression revealed increased anti-inflammatory and pro-homeostatic genes and decreases in expression of pro-inflammatory genes in …
Computational Modeling And Synthesis Of Pyridine Variants Of Benzoyl-Phenoxy-Acetamide With High Glioblastoma Cytotoxicity And Brain Tumor Penetration, Charles H. Ingraham, Joanna Stalinska, Sean C. Carson, Susan B. Colley, Monika Rak, Adam Lassak, Francesca Peruzzi, Krzysztof Reiss, Branko S. Jursic
Computational Modeling And Synthesis Of Pyridine Variants Of Benzoyl-Phenoxy-Acetamide With High Glioblastoma Cytotoxicity And Brain Tumor Penetration, Charles H. Ingraham, Joanna Stalinska, Sean C. Carson, Susan B. Colley, Monika Rak, Adam Lassak, Francesca Peruzzi, Krzysztof Reiss, Branko S. Jursic
School of Graduate Studies Faculty Publications
Glioblastomas are highly aggressive brain tumors for which therapeutic options are very limited. In a quest for new anti-glioblastoma drugs, we focused on specific structural modifications to the benzoyl-phenoxy-acetamide (BPA) structure present in a common lipid-lowering drug, fenofibrate, and in our first prototype glioblastoma drug, PP1. Here, we propose extensive computational analyses to improve the selection of the most effective glioblastoma drug candidates. Initially, over 100 structural BPA variations were analyzed and their physicochemical properties, such as water solubility (− logS), calculated partition coefficient (ClogP), probability for BBB crossing (BBB_SCORE), probability for CNS penetration (CNS-MPO) and calculated cardiotoxicity (hERG), were …
Targeting Mcl-1 By A Small Molecule Nsc260594 For Triple-Negative Breast Cancer Therapy, Shengli Dong, Margarite D. Matossian, Hassan Yousefi, Maninder Khosla, Bridgette M. Collins-Burow, Matthew E. Burow, Suresh K. Alahari
Targeting Mcl-1 By A Small Molecule Nsc260594 For Triple-Negative Breast Cancer Therapy, Shengli Dong, Margarite D. Matossian, Hassan Yousefi, Maninder Khosla, Bridgette M. Collins-Burow, Matthew E. Burow, Suresh K. Alahari
School of Graduate Studies Faculty Publications
Triple-negative breast cancers (TNBCs) are aggressive forms of breast cancer and tend to grow and spread more quickly than most other types of breast cancer. TNBCs can neither be targeted by hormonal therapies nor the antibody trastuzumab that targets the HER2 protein. There are urgent unmet medical needs to develop targeted drugs for TNBCs. We identified a small molecule NSC260594 from the NCI diversity set IV compound library. NSC260594 exhibited dramatic cytotoxicity in multiple TNBCs in a dose-and time-dependent manner. NSC260594 inhibited the Myeloid cell leukemia-1 (Mcl-1) expression through downregulation of Wnt signaling proteins. Consistent with this, NSC260594 treatment increased …
High Glucose-Upregulated Pd-L1 Expression Through Ras Signaling-Driven Downregulation Of Ptrh1 Leads To Suppression Of T Cell Cytotoxic Function In Tumor Environment, Chenggang Gao, Jiaoshun Chen, Jianwei Bai, Haoxiang Zhang, Yanyi Tao, Shihong Wu, Hehe Li, Heshui Wu, Qiang Shen, Tao Yin
High Glucose-Upregulated Pd-L1 Expression Through Ras Signaling-Driven Downregulation Of Ptrh1 Leads To Suppression Of T Cell Cytotoxic Function In Tumor Environment, Chenggang Gao, Jiaoshun Chen, Jianwei Bai, Haoxiang Zhang, Yanyi Tao, Shihong Wu, Hehe Li, Heshui Wu, Qiang Shen, Tao Yin
School of Graduate Studies Faculty Publications
Background: Nearly 80% of patients with pancreatic cancer suffer from glucose intolerance or diabetes. Pancreatic cancer complicated by diabetes has a more immunosuppressive tumor microenvironment (TME) and is associated with a worse prognosis. The relationship between glucose metabolism and programmed cell death-Ligand 1 (PD-L1) is close and complex. It is important to explore the regulation of high glucose on PD-L1 expression in pancreatic cancer and its effect on infiltrating immune effectors in the tumor microenvironment. Methods: Diabetic murine models (C57BL/6) were used to reveal different immune landscape in euglycemic and hyperglycemic pancreatic tumor microenvironment. Bioinformatics, WB, iRIP [Improved RNA Binding …
Cancer Cell-Specific Cgas/Sting Signaling Pathway In The Era Of Advancing Cancer Cell Biology, Vijay Kumar, Caitlin Bauer, John H. Stewart
Cancer Cell-Specific Cgas/Sting Signaling Pathway In The Era Of Advancing Cancer Cell Biology, Vijay Kumar, Caitlin Bauer, John H. Stewart
School of Graduate Studies Faculty Publications
Pattern-recognition receptors (PRRs) are critical to recognizing endogenous and exogenous threats to mount a protective proinflammatory innate immune response. PRRs may be located on the outer cell membrane, cytosol, and nucleus. The cGAS/STING signaling pathway is a cytosolic PRR system. Notably, cGAS is also present in the nucleus. The cGAS-mediated recognition of cytosolic dsDNA and its cleavage into cGAMP activates STING. Furthermore, STING activation through its downstream signaling triggers different interferon-stimulating genes (ISGs), initiating the release of type 1 interferons (IFNs) and NF-κB-mediated release of proinflammatory cytokines and molecules. Activating cGAS/STING generates type 1 IFN, which may prevent cellular transformation …
Yes-Associated Protein-1 Overexpression In Ocular Surface Squamous Neoplasia; A Potential Diagnostic Marker And Therapeutic Target, Peter Julius, Stepfanie N. Siyumbwa, Fred Maate, Phyllis Moonga, Guobin Kang, Trevor Kaile, John T. West, Charles Wood, Peter C. Angeletti
Yes-Associated Protein-1 Overexpression In Ocular Surface Squamous Neoplasia; A Potential Diagnostic Marker And Therapeutic Target, Peter Julius, Stepfanie N. Siyumbwa, Fred Maate, Phyllis Moonga, Guobin Kang, Trevor Kaile, John T. West, Charles Wood, Peter C. Angeletti
School of Graduate Studies Faculty Publications
Yes-associated protein-1 (YAP-1) is a Hippo system transcription factor, which serves as an oncogene in squamous cell carcinoma, and several solid tumors when the Hippo pathway is dysregulated. Yet, the activity of YAP-1 in ocular surface squamous neoplasia (OSSN) has not been determined. Here, we investigate the relationship between YAP-1 overexpression and OSSN. Using a cross-sectional study design, we recruited 227 OSSN patients from the University Teaching Hospitals in Lusaka, Zambia. Immunohistochemistry was used to assess YAP-1 protein overexpression in tumor tissue relative to surrounding benign squamous epithelium. OSSN patient samples (preinvasive, n = 62, 27% and invasive, n = …
Targeting Cgas/Sting Signaling-Mediated Myeloid Immune Cell Dysfunction In Time, Vijay Kumar, Caitlin Bauer, John H. Stewart
Targeting Cgas/Sting Signaling-Mediated Myeloid Immune Cell Dysfunction In Time, Vijay Kumar, Caitlin Bauer, John H. Stewart
School of Graduate Studies Faculty Publications
Myeloid immune cells (MICs) are potent innate immune cells serving as first responders to invading pathogens and internal changes to cellular homeostasis. Cancer is a stage of altered cellular homeostasis that can originate in response to different pathogens, chemical carcinogens, and internal genetic/epigenetic changes. MICs express several pattern recognition receptors (PRRs) on their membranes, cytosol, and organelles, recognizing systemic, tissue, and organ-specific altered homeostasis. cGAS/STING signaling is a cytosolic PRR system for identifying cytosolic double-stranded DNA (dsDNA) in a sequence-independent but size-dependent manner. The longer the cytosolic dsDNA size, the stronger the cGAS/STING signaling activation with increased type 1 interferon …
Systemic Review Of Clot Retraction Modulators, Alaina Guilbeau, Rinku Majumder
Systemic Review Of Clot Retraction Modulators, Alaina Guilbeau, Rinku Majumder
School of Graduate Studies Faculty Publications
Through a process termed clot retraction, platelets cause thrombi to shrink and become more stable. After platelets are activated via inside-out signaling, glycoprotein αIIbβIII binds to fibrinogen and initiates a cascade of intracellular signaling that ends in actin remodeling, which causes the platelet to change its shape. Clot retraction is also important for wound healing. Although the detailed molecular biology of clot retraction is only partially understood, various substances and physiological conditions modulate clot retraction. In this review, we describe some of the current literature pertaining to clot retraction modulators. In addition, we discuss compounds from Cudrania trucuspidata, Arctium lappa, …
A Novel Gardnerella, Prevotella, And Lactobacillus Standard That Improves Accuracy In Quantifying Bacterial Burden In Vaginal Microbial Communities, Jacob H. Elnaggar, Caleb M. Ardizzone, Nuno Cerca, Evelyn Toh, Paweł Łaniewski, Rebecca A. Lillis, Melissa M. Herbst-Kralovetz, Alison J. Quayle, Christina A. Muzny, Christopher M. Taylor
A Novel Gardnerella, Prevotella, And Lactobacillus Standard That Improves Accuracy In Quantifying Bacterial Burden In Vaginal Microbial Communities, Jacob H. Elnaggar, Caleb M. Ardizzone, Nuno Cerca, Evelyn Toh, Paweł Łaniewski, Rebecca A. Lillis, Melissa M. Herbst-Kralovetz, Alison J. Quayle, Christina A. Muzny, Christopher M. Taylor
School of Graduate Studies Faculty Publications
Bacterial vaginosis (BV) is the most common vaginal dysbiosis. In this condition, a polymicrobial biofilm develops on vaginal epithelial cells. Accurately quantifying the bacterial burden of the BV biofilm is necessary to further our understanding of BV pathogenesis. Historically, the standard for calculating total bacterial burden of the BV biofilm has been based on quantifying Escherichia coli 16S rRNA gene copy number. However, E. coli is improper for measuring the bacterial burden of this unique micro-environment. Here, we propose a novel qPCR standard to quantify bacterial burden in vaginal microbial communities, from an optimal state to a mature BV biofilm. …
Tumor Microenvironment As A Therapeutic Target In Melanoma Treatment, Naji Kharouf, Thomas W. Flanagan, Sofie Yasmin Hassan, Hosam Shalaby, Marla Khabaz, Sarah Lilly Hassan, Mosaad Megahed, Youssef Haikel, Simeon Santourlidis, Mohamed Hassan
Tumor Microenvironment As A Therapeutic Target In Melanoma Treatment, Naji Kharouf, Thomas W. Flanagan, Sofie Yasmin Hassan, Hosam Shalaby, Marla Khabaz, Sarah Lilly Hassan, Mosaad Megahed, Youssef Haikel, Simeon Santourlidis, Mohamed Hassan
School of Graduate Studies Faculty Publications
The role of the tumor microenvironment in tumor growth and therapy has recently attracted more attention in research and drug development. The ability of the microenvironment to trigger tumor maintenance, progression, and resistance is the main cause for treatment failure and tumor relapse. Accumulated evidence indicates that the maintenance and progression of tumor cells is determined by components of the microenvironment, which include stromal cells (endothelial cells, fibroblasts, mesenchymal stem cells, and immune cells), extracellular matrix (ECM), and soluble molecules (chemokines, cytokines, growth factors, and extracellular vesicles). As a solid tumor, melanoma is not only a tumor mass of monolithic …
Lipoxin A4 (Lxa4) Reduces Alkali-Induced Corneal Inflammation And Neovascularization And Upregulates A Repair Transcriptome, Jiucheng He, Thang L. Pham, Azucena H. Kakazu, Abhilash Ponnath, Khanh V. Do, Haydee E.P. Bazan
Lipoxin A4 (Lxa4) Reduces Alkali-Induced Corneal Inflammation And Neovascularization And Upregulates A Repair Transcriptome, Jiucheng He, Thang L. Pham, Azucena H. Kakazu, Abhilash Ponnath, Khanh V. Do, Haydee E.P. Bazan
School of Graduate Studies Faculty Publications
Purpose: To investigate the anti-inflammatory and anti-angiogenic effects of the bioactive lipid mediator LXA4 on a rat model of severe corneal alkali injury. Methods: To induce a corneal alkali injury in the right eyes of anesthetized Sprague Dawley rats. They were injured with a Φ 4 mm filter paper disc soaked in 1 N NaOH placed on the center of the cornea. After injury, the rats were treated topically with LXA4 (65 ng/20 μL) or vehicle three times a day for 14 days. Corneal opacity, neovascularization (NV), and hyphema were recorded and evaluated in a blind manner. Pro-inflammatory cytokine expression …
Study Of The Potential Toxicity Of Adrenaline To Neurons, Using The Sh-Sy5y Human Cellular Model, Vera Marisa Costa, João Paulo Capela, Maria Lourdes Bastos, Fernando Remião, Kurt James Varner, José Alberto Duarte, Félix Carvalho
Study Of The Potential Toxicity Of Adrenaline To Neurons, Using The Sh-Sy5y Human Cellular Model, Vera Marisa Costa, João Paulo Capela, Maria Lourdes Bastos, Fernando Remião, Kurt James Varner, José Alberto Duarte, Félix Carvalho
School of Graduate Studies Faculty Publications
Prolonged overexposure to catecholamines causes toxicity, usually credited to continuous adrenoceptor stimulation, autoxidation, and the formation of reactive pro-oxidant species. Non-differentiated SH-SY5Y cells were used to study the possible contribution of oxidative stress in adrenaline (ADR)-induced neurotoxicity, as a model to predict the toxicity of this catecholamine to peripheral nerves. Cells were exposed to several concentrations of ADR (0.1, 0.25, 0.5 and 1mM) and two cytotoxicity assays [lactate dehydrogenase (LDH) release and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction] were performed at several time-points (24, 48, and 96h). The cytotoxicity of ADR was concentration-and time-dependent in both assays, since the lowest concentration …
In Vitro Characterization Of A Novel Murine Model Of Cancerous Progression, Steven D. Scahill, Kelly Jean Sherman, Jessie J. Guidry, Whitney Walkowski, Theresa Nguyen, Durwood B. Ray, David H. Jones, Harry J. Gould, Dennis Paul
In Vitro Characterization Of A Novel Murine Model Of Cancerous Progression, Steven D. Scahill, Kelly Jean Sherman, Jessie J. Guidry, Whitney Walkowski, Theresa Nguyen, Durwood B. Ray, David H. Jones, Harry J. Gould, Dennis Paul
School of Graduate Studies Faculty Publications
To evaluate a potentially valuable tool to study cancer progression and metastasis, we characterized a novel murine model composed of a parental oncogene-transformed embryonic fibroblast line and five cell lines isolated from progressively advanced tumors. Lines derived from distant metastases displayed significantly greater rates of motility, invasiveness, and extracellular acidification than lines derived from a primary tumor or local metastases. A comprehensive proteomic analysis of these cells showed numerous oncogenes to be upregulated and tumor suppressors to be downregulated in the advanced lines, and provided novel targets for future examination. The first cell line capable of extravasation displayed particularly high …
Moerv14 Mediates The Intracellular Transport Of Cell Membrane Receptors To Govern The Appressorial Formation And Pathogenicity Of Magnaporthe Oryzae, Bin Qian, Xiaotong Su, Ziyuan Ye, Xinyu Liu, Muxing Liu, Haifeng Zhang, Ping Wang, Zhengguang Zhang
Moerv14 Mediates The Intracellular Transport Of Cell Membrane Receptors To Govern The Appressorial Formation And Pathogenicity Of Magnaporthe Oryzae, Bin Qian, Xiaotong Su, Ziyuan Ye, Xinyu Liu, Muxing Liu, Haifeng Zhang, Ping Wang, Zhengguang Zhang
School of Graduate Studies Faculty Publications
Magnaporthe oryzae causes rice blasts posing serious threats to food security worldwide. During infection, M. oryzae utilizes several transmembrane receptor proteins that sense cell surface cues to induce highly specialized infectious structures called appressoria. However, little is known about the mechanisms of intracellular receptor tracking and their function. Here, we described that disrupting the coat protein complex II (COPII) cargo protein MoErv14 severely affects appressorium formation and pathogenicity as the ΔMoerv14 mutant is defective not only in cAMP production but also in the phosphorylation of the mitogen-activated protein kinase (MAPK) MoPmk1. Studies also showed that either externally supplementing cAMP or …
The Non-Coding Rna Journal Club: Highlights On Recent Papers—12, Patrick K.T. Shiu, Mirolyuba Ilieva, Anja Holm, Shizuka Uchida, Johanna K. Distefano, Agnieszka Bronisz, Ling Yang, Yoh Asahi, Ajay Goel, Liuqing Yang, Ashok Nuthanakanti, Alexander Serganov, Suresh K. Alahari, Chunru Lin, Barbara Pardini, Alessio Naccarati, Jing Jin, Beshoy Armanios, Xiao Bo Zhong, Nikolaos Sideris, Salih Bayraktar, Leandro Castellano, André P. Gerber, He Lin, Simon J. Conn, Doha Magdy Mostafa Sleem
The Non-Coding Rna Journal Club: Highlights On Recent Papers—12, Patrick K.T. Shiu, Mirolyuba Ilieva, Anja Holm, Shizuka Uchida, Johanna K. Distefano, Agnieszka Bronisz, Ling Yang, Yoh Asahi, Ajay Goel, Liuqing Yang, Ashok Nuthanakanti, Alexander Serganov, Suresh K. Alahari, Chunru Lin, Barbara Pardini, Alessio Naccarati, Jing Jin, Beshoy Armanios, Xiao Bo Zhong, Nikolaos Sideris, Salih Bayraktar, Leandro Castellano, André P. Gerber, He Lin, Simon J. Conn, Doha Magdy Mostafa Sleem
School of Graduate Studies Faculty Publications
No abstract provided.
Hpv-Related Anal Cancer Is Associated With Changes In The Anorectal Microbiome During Cancer Development, Jacob H. Elnaggar, Victoria O. Huynh, Daniel Lin, R. Tyler Hillman, Chike O. Abana, Molly B. El Alam, Katarina C. Tomasic, Tatiana V. Karpinets, Ramez Kouzy, Jae L. Phan, Jennifer Wargo, Emma B. Holliday, Prajnan Das, Melissa P. Mezzari, Nadim J. Ajami, Erica J. Lynn, Bruce D. Minsky, Van K. Morris, Andrea Milbourne, Craig A. Messick, Ann H. Klopp, P. Andrew Futreal, Cullen M. Taniguchi, Kathleen M. Schmeler, Lauren E. Colbert
Hpv-Related Anal Cancer Is Associated With Changes In The Anorectal Microbiome During Cancer Development, Jacob H. Elnaggar, Victoria O. Huynh, Daniel Lin, R. Tyler Hillman, Chike O. Abana, Molly B. El Alam, Katarina C. Tomasic, Tatiana V. Karpinets, Ramez Kouzy, Jae L. Phan, Jennifer Wargo, Emma B. Holliday, Prajnan Das, Melissa P. Mezzari, Nadim J. Ajami, Erica J. Lynn, Bruce D. Minsky, Van K. Morris, Andrea Milbourne, Craig A. Messick, Ann H. Klopp, P. Andrew Futreal, Cullen M. Taniguchi, Kathleen M. Schmeler, Lauren E. Colbert
School of Graduate Studies Faculty Publications
Background: Squamous cell carcinoma of the anus (SCCA) is a rare gastrointestinal cancer. Factors associated with progression of HPV infection to anal dysplasia and cancer are unclear and screening guidelines and approaches for anal dysplasia are less clear than for cervical dysplasia. One potential contributing factor is the anorectal microbiome. In this study, we aimed to identify differences in anal microbiome composition in the settings of HPV infection, anal dysplasia, and anal cancer in this rare disease. Methods: Patients were enrolled in two prospective studies. Patients with anal dysplasia were part of a cross-sectional cohort that enrolled women with high-grade …
Impact Of Testosterone Use On The Vaginal Microbiota Of Transgender Men, Including Susceptibility To Bacterial Vaginosis: Study Protocol For A Prospective, Observational Study, Christina A. Muzny, Olivia T. Van Gerwen, Julia A. Schroeder, Emma Sophia Kay-Duncan, Krishmita Siwakoti, Kristal J. Aaron, Isaac C. Eastlund, Keonte J. Graves, Jacob H. Elnaggar, Ashutosh Tamhane, Dustin Long, Nicholas Van Wagoner, Evelyn Toh, Christopher M. Taylor
Impact Of Testosterone Use On The Vaginal Microbiota Of Transgender Men, Including Susceptibility To Bacterial Vaginosis: Study Protocol For A Prospective, Observational Study, Christina A. Muzny, Olivia T. Van Gerwen, Julia A. Schroeder, Emma Sophia Kay-Duncan, Krishmita Siwakoti, Kristal J. Aaron, Isaac C. Eastlund, Keonte J. Graves, Jacob H. Elnaggar, Ashutosh Tamhane, Dustin Long, Nicholas Van Wagoner, Evelyn Toh, Christopher M. Taylor
School of Graduate Studies Faculty Publications
Introduction The effect of testosterone (T) therapy on the vaginal microbiota of transgender men (TGM) is not well characterised, although one cross-sectional study comparing the vaginal microbiota of cisgender women to TGM on T≥1 year found that, in 71% of the TGM, the vaginal microbiota was less likely to be Lactobacillus-dominated and more likely to be enriched with >30 other bacterial species, many associated with bacterial vaginosis (BV). This prospective study aims to investigate changes in the composition of the vaginal microbiota over time in TGM who retain their natal genitalia (ie, vagina) and initiate T. In addition, we will …