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Grand Valley State University

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Biodegradable Magnesium Materials Regulate Ros-Rns Balance In Pro-Inflammatory Macrophage Environment, Maria P. Kwesiga, Amani A. Gillette, Fatemeh Razaviamri, Margaret E. Plank, Alexia L. Canull, Zachary Alesch, Weilue He, Bruce P. Lee, Roger J. Guillory Ii Nov 2022

Biodegradable Magnesium Materials Regulate Ros-Rns Balance In Pro-Inflammatory Macrophage Environment, Maria P. Kwesiga, Amani A. Gillette, Fatemeh Razaviamri, Margaret E. Plank, Alexia L. Canull, Zachary Alesch, Weilue He, Bruce P. Lee, Roger J. Guillory Ii

Peer Reviewed Articles

The relationship between reactive oxygen and nitrogen species (ROS-RNS) secretion and the concomitant biocorrosion of degradable magnesium (Mg) materials is poorly understood. We found that Mg foils implanted short term in vivo (24 h) displayed large amounts of proinflammatory F4/80+/iNOS + macrophages at the interface. We sought to investigate the interplay between biodegrading Mg materials (98.6% Mg, AZ31 & AZ61) and macrophages (RAW 264.7) stimulated with lipopolysaccharide (RAW 264.7LPS) to induce ROS-RNS secretion. To test how these proinflammatory ROS-RNS secreting cells interact with Mg corrosion in vitro, Mg and AZ61 discs were suspended approximately 2 mm above a …


In-Vivo Evaluation Of Molybdenum As Bioabsorbable Stent Candidate, Malgorzata Sikora-Jasinska, Lea M. Morath, Maria P. Kwesiga, Margaret E. Plank, Alexia L. Nelson, Alexander A. Oliver, Martin L. Bocks, Roger J. Guillory Ii, Jeremy Goldman Nov 2021

In-Vivo Evaluation Of Molybdenum As Bioabsorbable Stent Candidate, Malgorzata Sikora-Jasinska, Lea M. Morath, Maria P. Kwesiga, Margaret E. Plank, Alexia L. Nelson, Alexander A. Oliver, Martin L. Bocks, Roger J. Guillory Ii, Jeremy Goldman

Peer Reviewed Articles

Biodegradable stents have tremendous theoretical potential as an alternative to bare metal stents and drugeluting stents for the treatment of obstructive coronary artery disease. Any bioresorbable or biodegradable scaffold material needs to possess optimal mechanical properties and uniform degradation behavior that avoids local and systemic toxicity. Recently, molybdenum (Mo) has been investigated as a potential novel biodegradable material for this purpose. With its proven moderate degradation rate and excellent mechanical properties, Mo may represent an ideal source material for clinical cardiac and vascular applications. The present study was performed to evaluate the mechanical performance of metallic Mo in vitro and …


Galectin-3 Mediated Inflammatory Response Contributes To Neurological Recovery By Qishenyiqi In Subacute Stroke Model, Yule Wang, Shuang He, Xinyan Liu, Zhixiong Li, Lin Zhu, Guangxu Xiao, Xiaoli Du, Hongxia Du, Wen Zhang, Yiqian Zhang, John Orgah, Benjamin Feng, Boli Zhang, Yan Zhu Apr 2021

Galectin-3 Mediated Inflammatory Response Contributes To Neurological Recovery By Qishenyiqi In Subacute Stroke Model, Yule Wang, Shuang He, Xinyan Liu, Zhixiong Li, Lin Zhu, Guangxu Xiao, Xiaoli Du, Hongxia Du, Wen Zhang, Yiqian Zhang, John Orgah, Benjamin Feng, Boli Zhang, Yan Zhu

Peer Reviewed Articles

Effective therapies for stroke are still limited due to its complex pathological manifestations. QiShenYiQi (QSYQ), a component-based Chinese medicine capable of reducing organ injury caused by ischemia/reperfusion, may offer an alternative option for stroke treatment and post-stroke recovery. Recently, we reported a beneficial effect of QSYQ for acute stroke via modulation of the neuroinflammatory response. However, if QSYQ plays a role in subacute stroke remains unknown. The pharmacological action of QSYQ was investigated in experimental stroke rats which underwent 90 min ischemia and 8 days reperfusion in this study. Neurological and locomotive deficits, cerebral infarction, brain edema, and BBB integrity …


Paeoniflorin And Hydroxysafflor Yellow A In Xuebijing Injection Attenuate Sepsis-Induced Cardiac Dysfunction And Inhibit Proinflammatory Cytokine Production, Xin-Tong Wang, Zhen Peng, Ying-Ying An, Ting Shang, Guangxu Xiao, Shuang He, Xi Chen, Hang Zhang, Tao Wang, Jun-Hua Zhang, Xiumei Gao, Yan Zhu, Benjamin Feng Apr 2021

Paeoniflorin And Hydroxysafflor Yellow A In Xuebijing Injection Attenuate Sepsis-Induced Cardiac Dysfunction And Inhibit Proinflammatory Cytokine Production, Xin-Tong Wang, Zhen Peng, Ying-Ying An, Ting Shang, Guangxu Xiao, Shuang He, Xi Chen, Hang Zhang, Tao Wang, Jun-Hua Zhang, Xiumei Gao, Yan Zhu, Benjamin Feng

Peer Reviewed Articles

Sepsis-induced myocardial dysfunction is a major contributor to the poor outcomes of septic shock. As an add-on with conventional sepsis management for over 15 years, the effect of Xuebijing injection (XBJ) on the sepsis-induced myocardial dysfunction was not well understood. The material basis of Xuebijing injection (XBJ) in managing infections and infection-related complications remains to be defined. A murine cecal ligation and puncture (CLP) model and cardiomyocytes in vitro culture were adopted to study the influence of XBJ on infection-induced cardiac dysfunction. XBJ significantly improved the survival of septic-mice and rescued cardiac dysfunction in vivo. RNA-seq revealed XBJ attenuated …


Protecting Intestinal Microenvironment Alleviates Acute Graft-Versus-Host Disease, Zhengcan Zhou, Ting Shang, Xiurong Li, Hongyan Zhu, Yu-Bo Qi, Xin Zhao, Xi Chen, Zhe-Xin Shi, Guixiang Pan, Yue-Fei Wang, Guanwei Fan, Xiumei Gao, Yan Zhu, Benjamin Feng Feb 2021

Protecting Intestinal Microenvironment Alleviates Acute Graft-Versus-Host Disease, Zhengcan Zhou, Ting Shang, Xiurong Li, Hongyan Zhu, Yu-Bo Qi, Xin Zhao, Xi Chen, Zhe-Xin Shi, Guixiang Pan, Yue-Fei Wang, Guanwei Fan, Xiumei Gao, Yan Zhu, Benjamin Feng

Peer Reviewed Articles

Acute gut graft-versus-host disease (aGVHD) is a leading threat to the survival of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Abnormal gut microbiota is correlated with poor prognosis in allo-HSCT recipients. A disrupted intestinal microenvironment exacerbates dysbiosis in GVHD patients. We hypothesized that maintaining the integrity of the intestinal barrier may protect gut microbiota and attenuate aGVHD. This hypothesis was tested in a murine aGVHD model and an in vitro intestinal epithelial culture. Millipore cytokine array was utilized to determine the expression of proinflammatory cytokines in the serum. The 16S rRNA sequencing was used to determine the abundance and diversity …


Shuxuening Injection Facilitates Neurofunctional Recovery Via Down-Regulation Of G-Csf-Mediated Granulocyte Adhesion And Diapedesis Pathway In A Subacute Stroke Mouse Model, Zhixiong Li, Guangxu Xiao, Ming Lyu, Yule Wang, Shuang He, Hongxia Du, Xintong Wang, Benjamin Feng, Yan Zhu May 2020

Shuxuening Injection Facilitates Neurofunctional Recovery Via Down-Regulation Of G-Csf-Mediated Granulocyte Adhesion And Diapedesis Pathway In A Subacute Stroke Mouse Model, Zhixiong Li, Guangxu Xiao, Ming Lyu, Yule Wang, Shuang He, Hongxia Du, Xintong Wang, Benjamin Feng, Yan Zhu

Peer Reviewed Articles

Post-stroke neural damage is a serious health concern which does not yet have an effective treatment. We have shown previously that Shuxuening injection (SXNI), a Ginkgo biloba extract-based natural medicine, protects brain after an acute ischemic stroke, but its efficacy for post-stroke recovery is not known. This study was to investigate whether SXNI can improve the prognosis of stroke at a subacute phase. Mice with cerebral ischemia-reperfusion injury (CIRI) were established by middle cerebral artery occlusion (MCAO), and drugs or saline were injected by the tail vein every 12 h after reperfusion. The therapeutic effect of SXNI was evaluated by …


What Smells? Developing In-Field Methods To Characterize The Chemical Composition Of Wild Mammalian Scent Cues, Cynthia Thompson, Kimberly N. Bottenberg, Andrew W. Lantz, Maria A B De Oliveira, Leonardo C O Melo, Christopher J. Vinyard Apr 2020

What Smells? Developing In-Field Methods To Characterize The Chemical Composition Of Wild Mammalian Scent Cues, Cynthia Thompson, Kimberly N. Bottenberg, Andrew W. Lantz, Maria A B De Oliveira, Leonardo C O Melo, Christopher J. Vinyard

Peer Reviewed Articles

Olfactory cues play an important role in mammalian biology, but have been challenging to assess in the field. Current methods pose problematic issues with sample storage and transportation, limiting our ability to connect chemical variation in scents with relevant ecological and behavioral contexts. Real-time, in-field analysis via portable gas chromatography–mass spectrometry (GC-MS) has the potential to overcome these issues, but with trade-offs of reduced sensitivity and compound mass range. We field-tested the ability of portable GC-MS to support two representative applications of chemical ecology research with a wild arboreal primate, common marmoset monkeys (Callithrix jacchus). We developed methods …


Protection Against Acute Cerebral Ischemia/Reperfusion Injury By Qishenyiqi Via Neuroinflammatory Network Mobilization, Yule Wang, Guangxu Xiao, Xhuang He, Xinyan Liu, Lin Zhu, Xinyue Yang, Yiqian Zhang, John Orgah, Benjamin Feng, Xiaoying Wang, Boli Zhang, Yan Zhu Feb 2020

Protection Against Acute Cerebral Ischemia/Reperfusion Injury By Qishenyiqi Via Neuroinflammatory Network Mobilization, Yule Wang, Guangxu Xiao, Xhuang He, Xinyan Liu, Lin Zhu, Xinyue Yang, Yiqian Zhang, John Orgah, Benjamin Feng, Xiaoying Wang, Boli Zhang, Yan Zhu

Peer Reviewed Articles

Cerebral ischemia/reperfusion injury (CI/RI) is a common feature of ischemic stroke, involving a period of impaired blood supply to the brain, followed by the restoration of cerebral perfusion through medical intervention. Although ischemia and reperfusion brain damage is a complex pathological process with an unclear physiological mechanism, more attention is currently focused on the neuroinflammatory response of an ischemia/reperfusion origin, and anti-inflammatory appears to be a potential therapeutic strategy following ischemic stroke. QiShenYiQi (QSYQ), a component-based Chinese medicine with Qi-tonifying and blood-activating property, has pharmacological actions of anti-inflammatory, antioxidant, mitochondrial protectant, anti-apoptosis, and antiplatelet aggregation. We have previously reported that …


Xuebijing Injection Maintains Grp78 Expression To Prevent Candida Albicans–Induced Epithelial Death In The Kidney, Ting Shang, Qilin Yu, Tongtong Ren, Xin-Tong Wang, Hongyan Zhu, Jia-Ming Gao, Guixiang Pan, Xiumei Gao, Yan Zhu, Benjamin Feng, Ming-Chun Li Jan 2020

Xuebijing Injection Maintains Grp78 Expression To Prevent Candida Albicans–Induced Epithelial Death In The Kidney, Ting Shang, Qilin Yu, Tongtong Ren, Xin-Tong Wang, Hongyan Zhu, Jia-Ming Gao, Guixiang Pan, Xiumei Gao, Yan Zhu, Benjamin Feng, Ming-Chun Li

Peer Reviewed Articles

Sepsis and septic shock threaten the survival of millions of patients in the intensive care unit. Secondary fungal infections significantly increased the risk of mortality in sepsis patients. Chinese medicine Xuebijing injection (XBJ) has been routinely used as an add-on treatment to sepsis and septic shock in China. Our network pharmacology analysis predicted that XBJ also influences fungal infection, consisting with results of pioneer clinical studies. We conducted in vivo and in vitro experiments to verify this prediction. To our surprise, XBJ rescued mice from lethal Candida sepsis in a disseminated Candida albicans infection model and abolished the colonization of …


Bridge To Neuroscience Workshop: An Effective Educational Tool To Introduce Principles Of Neuroscience To Hispanics Students, Alexandra Colon-Rodriguez, Chelsea T. Tiernan, Eileen S. Rodriguez-Tapia, William D. Atchison Dec 2019

Bridge To Neuroscience Workshop: An Effective Educational Tool To Introduce Principles Of Neuroscience To Hispanics Students, Alexandra Colon-Rodriguez, Chelsea T. Tiernan, Eileen S. Rodriguez-Tapia, William D. Atchison

Peer Reviewed Articles

Neuroscience as a discipline is rarely covered in educational institutions in Puerto Rico. In an effort to overcome this deficit we developed the Bridge to Neuroscience Workshop (BNW), a full-day hands-on workshop in neuroscience education. BNW was conceived as an auxiliary component of a parent recruitment program called Bridge to the PhD in Neuroscience Program (BPNP). The objectives of BNW are to identify promising students for BPNP, and to increase awareness of neuroscience as a discipline and a career option. BNW introduces basic concepts in neuroscience using a variety of educational techniques, including mini-lectures, interactive discussions, case studies, experimentation, and …


Reconstructing Birth In Australopithecus Sediba, Natalie M. Laudicina, Frankee Rodriguez, Jeremy M. Desilva Sep 2019

Reconstructing Birth In Australopithecus Sediba, Natalie M. Laudicina, Frankee Rodriguez, Jeremy M. Desilva

Peer Reviewed Articles

Hominin birth mechanics have been examined and debated from limited and often fragmentary fossil pelvic material. Some have proposed that birth in the early hominin genus Australopithecus was relatively easy and ape-like, while others have argued for a more complex, human-like birth mechanism in australopiths. Still others have hypothesized a unique birth mechanism, with no known modern equivalent. Preliminary work on the pelvis of the recently discovered 1.98 million-year-old hominin Australopithecus sediba found it to possess a unique combination of Homo and Australopithecus-like features. Here, we create a composite pelvis of Australopithecus sediba to reconstruct the birth process in …


Defective Transcriptional Programming Of Effector Cd8 T Cells In Aged Mice Is Cell-Extrinsic And Can Be Corrected By Administration Of Il-12 And Il-18, Mladen Jergovic, Heather L. Thompson, Kristin R. Renkema, Megan J. Smithey, Janko Nikolich-Zugich Sep 2019

Defective Transcriptional Programming Of Effector Cd8 T Cells In Aged Mice Is Cell-Extrinsic And Can Be Corrected By Administration Of Il-12 And Il-18, Mladen Jergovic, Heather L. Thompson, Kristin R. Renkema, Megan J. Smithey, Janko Nikolich-Zugich

Peer Reviewed Articles

In response to infection with intracellular microorganisms, old mice mobilize decreased numbers of antigen-specific CD8 T cells with reduced expression of effector molecules and impaired cytolytic activity. Molecular mechanisms behind these defects and the cell-intrinsic (affecting naïve CD8 T cells themselves) vs. extrinsic, microenvironmental origin of such defects remain unclear. Using reciprocal transfer experiments of highly purified naïve T cells from adult and old transgenic OT-1 mice, we decisively show that the dominant effect is cell-extrinsic. Naïve adult OT-1 T cells failed to expand and terminally differentiate in the old organism infected with Listeria-OVA. This defect was preceded by …


Untargeted Safety Pharmacology Screen Of Blood-Activating And Stasis-Removing Patent Chinese Herbal Medicines Identified Nonherbal Ingredients As A Cause Of Organ Damage In Experimental Models, Xinyan Liu, Rui Shao, Xinyue Yang, Guangxu Xiao, Shuang He, Benjamin Feng, Yan Zhu Sep 2019

Untargeted Safety Pharmacology Screen Of Blood-Activating And Stasis-Removing Patent Chinese Herbal Medicines Identified Nonherbal Ingredients As A Cause Of Organ Damage In Experimental Models, Xinyan Liu, Rui Shao, Xinyue Yang, Guangxu Xiao, Shuang He, Benjamin Feng, Yan Zhu

Peer Reviewed Articles

Blood activation and stasis removal from circulation is a central principle for treatment of syndromes related to cerebral and cardiovascular diseases in Chinese herbal medicine. However, blood-activating and stasis-removing patent Chinese herbal medicine (BASR-pCHM) widely used with or without prescription in China and elsewhere are highly variable in composition and manufacture standard, making their safety assessment a challenging task. We proposed that an integrated evaluation of multiple toxicity parameters of BASR-pCHM would provide critical reference and guidelines for their safe clinical application. Examination of standardized extracts from 58 compound BASR-pCHM in vivo in VEGFR2-luc mice and in vitro in cardiac, …


Astragaloside Iii Enhances Anti-Tumor Response Of Nk Cells By Elevating Nkg2d And Ifn-Γ, Xingmeng Chen, Xi Chen, Junxiao Gao, Han Yang, Yue Duan, Benjamin Feng, Xin He, Xiaoqun Gong, Hanjie Wang, Xiaoli Wu, Jin Chang Aug 2019

Astragaloside Iii Enhances Anti-Tumor Response Of Nk Cells By Elevating Nkg2d And Ifn-Γ, Xingmeng Chen, Xi Chen, Junxiao Gao, Han Yang, Yue Duan, Benjamin Feng, Xin He, Xiaoqun Gong, Hanjie Wang, Xiaoli Wu, Jin Chang

Peer Reviewed Articles

Natural killer (NK) cells play an irreplaceable role in the development of colon cancer, in which antitumor function of NK cells was impaired. Astragaloside III is a natural compound from Astragalus that has been shown to have immunomodulatory effects in various systems. However, few studies have evaluated the antitumor effects of Astragaloside III through stimulating systemic immunity and regulating NK cells. In this study, flow cytometry, immunohistochemical analysis, and immunofunctional assays were performed to elucidate the functions of Astragaloside III in restoring antitumor function of NK cells. We demonstrated that Astragaloside III significantly elevated the expression of natural killer group …


Protein Structure Analysis, Agnieszka Szarecka, Chris Dobson Aug 2019

Protein Structure Analysis, Agnieszka Szarecka, Chris Dobson

Peer Reviewed Articles

We describe a series of engaging exercises in which students emulate the process that researchers use to efficiently develop new pharmaceutical drugs, that of rational drug design. The activities are taken from a three- to four-hour workshop regularly conducted with first-year college students and presented here to take place over three to four class periods. Although targeted at college students, these activities may be appropriate at the high school level as well, particularly in an AP Biology course. The exercises introduce students to the topics of bioinformatics and computer modeling, in the context of rational drug design, using free online …


Disruption Of Valosin-Containing Protein Activity Causes Cardiomyopathy And Reveals Pleiotropic Functions In Cardiac Homeostasis, Matthew J. Brody, Davy Vanhoutte, Chinmay V. Bakshi, Ruijie Liu, Robert N. Correll, Michelle A. Sargent, Jeffery D. Molkentin May 2019

Disruption Of Valosin-Containing Protein Activity Causes Cardiomyopathy And Reveals Pleiotropic Functions In Cardiac Homeostasis, Matthew J. Brody, Davy Vanhoutte, Chinmay V. Bakshi, Ruijie Liu, Robert N. Correll, Michelle A. Sargent, Jeffery D. Molkentin

Peer Reviewed Articles

Valosin-containing protein (VCP), also known as p97, is an ATPase with diverse cellular functions, although the most highly characterized is targeting of misfolded or aggregated proteins to degradation pathways, including the endoplasmic reticulum–associated degradation (ERAD) pathway. However, how VCP functions in the heart has not been carefully examined despite the fact that human mutations in VCP cause Paget disease of bone and frontotemporal dementia, an autosomal dominant multisystem proteinopathy that includes disease in the heart, skeletal muscle, brain, and bone. Here we generated heart-specific transgenic mice overexpressing WT VCP or a VCPK524A mutant with deficient ATPase activity. Transgenic mice …


A Simplified Led-Driven Switch For Fast-Scan Controlled-Adsorption Voltammetry Instrumentation, Rhiannon Robke, Parastoo Hashemi, Eric Ramsson Apr 2019

A Simplified Led-Driven Switch For Fast-Scan Controlled-Adsorption Voltammetry Instrumentation, Rhiannon Robke, Parastoo Hashemi, Eric Ramsson

Peer Reviewed Articles

Fast-scan cyclic voltammetry (FSCV) is an analytical tool used to probe neurochemical processes in real-time. A major drawback for specialized applications of FSCV is that instrumentation must be constructed or modified in-house by those with expertise in electronics. One such specialized application is the newly developed fast-scan controlled-adsorption voltammetry (FSCAV) that measures basal (tonic) in vivo dopamine and serotonin concentrations. FSCAV requires additional software and equipment (an operational amplifier coupled to a transistor-transistor logic) allowing the system to switch between applying a FSCV waveform and a constant potential to the working electrode. Herein we describe a novel, simplified switching component …


Development Of A Breadfruit Flour Pasta Product, Carmen L. Nochera, Diane Ragone Mar 2019

Development Of A Breadfruit Flour Pasta Product, Carmen L. Nochera, Diane Ragone

Peer Reviewed Articles

Breadfruit (Artocarpus altilis) is grown throughout the tropics. Processing the perishable starchy fruit into flour provides a means to expand the use of the fruit. The flour can be used to develop new value-added products for local use and potential export. The purpose of this investigation was to develop a pasta product using breadfruit flour, test the sensory qualities of the breadfruit pasta product by sensory evaluation, and evaluate the nutritional composition. ‘Ma’afala’, a popular and widely distributed Polynesian cultivar was used for the study. Nutritional labeling shows that the breadfruit pasta product is high in carbohydrates (73.3%/100 …


Network Pharmacology-Guided Development Of A Novel Integrative Regimen To Prevent Acute Graft-Vs.-Host Disease, Ming Lyu, Zhengcan Zhou, Xiaoming Wang, Hong Lv, Mei Wang, Guixiang Pan, Yuefei Wang, Guanwei Fan, Xiumei Gao, Benjamin Feng, Yan Zhu Dec 2018

Network Pharmacology-Guided Development Of A Novel Integrative Regimen To Prevent Acute Graft-Vs.-Host Disease, Ming Lyu, Zhengcan Zhou, Xiaoming Wang, Hong Lv, Mei Wang, Guixiang Pan, Yuefei Wang, Guanwei Fan, Xiumei Gao, Benjamin Feng, Yan Zhu

Peer Reviewed Articles

Lapses in the graft-vs.-host disease (GVHD) prophylaxis and side effects of current standard care following allogeneic hematopoietic stem cell transplantation (allo-HSCT) call for novel regimens. Traditional approaches targeting T cells showed limited success in preventing acute GVHD (aGVHD). System medicine showed promising results treating complex diseases such as sepsis and multi-organ dysfunction syndrome (MODS). Adapting established network pharmacology analysis methods, we aimed to develop novel integrative regimens to prevent aGVHD. Our network pharmacology analysis predicted that Xuebijing injection (XBJ) targets a series of key node proteins in aGVHD network. It also unveiled that Salviae miltiorrhizae (Danshen), an herb in Xuebijing …


Investigative Study On Nitric Oxide Production In Human Dermal Fibroblast Cells Under Normal And High Glucose Conditions, Maria P. Kwesiga, Emily Cook, Jennifer Hannon, Sarah Wayward, Caroline Gwaltney, Smitha Rao, Megan Frost Nov 2018

Investigative Study On Nitric Oxide Production In Human Dermal Fibroblast Cells Under Normal And High Glucose Conditions, Maria P. Kwesiga, Emily Cook, Jennifer Hannon, Sarah Wayward, Caroline Gwaltney, Smitha Rao, Megan Frost

Peer Reviewed Articles

Diabetic foot ulcers (DFU) are a major health problem associated with diabetes mellitus. Impaired nitric oxide (NO) production has been shown to be a major contributor to the dysregulation of healing in DFU. The level of impairment is not known primarily due to challenges with measuring NO. Herein, we report the actual level of NO produced by human dermal fibroblasts cultured under normal and high glucose conditions. Fibroblasts produce the extracellular matrix, which facilitate the migration of keratinocytes to close wounds. The results show that NO production was significantly higher in normal glucose compared to high glucose conditions. The real-time …


Role Of The Fractalkine Receptor In Cns Autoimmune Inflammation: New Approach Utilizing A Mouse Model Expressing The Human Cx3cr1I249/M280 Variant, Sandra M. Cardona, Sangwon V. Kim, Kaira A. Church, Vanessa O. Torres, Ian A. Cleary, Andrew S. Mendiola, Stephen P. Saville, Stephanie S. Watowich, Jan Parker-Thornburg, Alejandro Soto-Ospina, Richard M. Ransohoff, Astrid E. Cardona Oct 2018

Role Of The Fractalkine Receptor In Cns Autoimmune Inflammation: New Approach Utilizing A Mouse Model Expressing The Human Cx3cr1I249/M280 Variant, Sandra M. Cardona, Sangwon V. Kim, Kaira A. Church, Vanessa O. Torres, Ian A. Cleary, Andrew S. Mendiola, Stephen P. Saville, Stephanie S. Watowich, Jan Parker-Thornburg, Alejandro Soto-Ospina, Richard M. Ransohoff, Astrid E. Cardona

Peer Reviewed Articles

Multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS) is the leading cause of non-traumatic neurological disability in young adults. Immune mediated destruction of myelin and oligodendrocytes is considered the primary pathology of MS, but progressive axonal loss is the major cause of neurological disability. In an effort to understand microglia function during CNS inflammation, our laboratory focuses on the fractalkine/CX3CR1 signaling as a regulator of microglia neurotoxicity in various models of neurodegeneration. Fractalkine (FKN) is a transmembrane chemokine expressed in the CNS by neurons and signals through its unique receptor CX3CR1 present in microglia. During …


Combined Mtor And Mek Inhibition Is An Effective Therapy In A Novel Mouse Model For Angiosarcoma, Michelle L. Chadwick, Adam Lane, Dana Thomas, Amanda R. Smith, Angela R. White, Dominique Davidson, Benjamin Feng, Elisa Boscolo, Yi Zheng, Denise M. Adams, Anita Gupta, Andre Veillette, Lionel M L Chow May 2018

Combined Mtor And Mek Inhibition Is An Effective Therapy In A Novel Mouse Model For Angiosarcoma, Michelle L. Chadwick, Adam Lane, Dana Thomas, Amanda R. Smith, Angela R. White, Dominique Davidson, Benjamin Feng, Elisa Boscolo, Yi Zheng, Denise M. Adams, Anita Gupta, Andre Veillette, Lionel M L Chow

Peer Reviewed Articles

Angiosarcoma is an aggressive malignancy of vascular origin that occurs de novo or in the context of previous cancer therapy. Despite multi-modal aggressive treatment including surgical resection, chemotherapy, and radiation, five-year overall survival remains poor at 35%. Due to its rarity, little is known about its molecular pathology and clinical trials have been extremely difficult to conduct. Development of animal models for rare diseases like angiosarcoma is critical to improve our understanding of tumorigenesis and to test novel treatment regimens. A genetically engineered mouse model for angiosarcoma was generated by conditional deletion of Trp53, Pten, and Ptpn12 in …


An Individualized, Perception-Based Protocol To Investigate Human Physiological Responses To Cooling, Crystal L. Coolbaugh, Emily C. Bush, Elizabeth S. Galenti, E Brian Welch, Theodore F. Towse Mar 2018

An Individualized, Perception-Based Protocol To Investigate Human Physiological Responses To Cooling, Crystal L. Coolbaugh, Emily C. Bush, Elizabeth S. Galenti, E Brian Welch, Theodore F. Towse

Peer Reviewed Articles

Cold exposure, a known stimulant of the thermogenic effects of brown adipose tissue (BAT), is the most widely used method to study BAT physiology in adult humans. Recently, individualized cooling has been recommended to standardize the physiological cold stress applied across participants, but critical experimental details remain unclear. The purpose of this work was to develop a detailed methodology for an individualized, perception-based protocol to investigate human physiological responses to cooling. Participants were wrapped in two water-circulating blankets and fitted with skin temperature probes to estimate BAT activity and peripheral vasoconstriction. We created a thermoesthesia graphical user interface (tGUI) to …


General Survey Of Fructus Psoraleae From The Different Origins And Chemical Identification Of The Roasted From Raw Fructus Psoraleae, Junjun Yang, Jing Yang, Jie Du, Benjamin Feng, Xin Chai, Mingming Xiao, Yuefei Wang, Xiumei Gao Dec 2017

General Survey Of Fructus Psoraleae From The Different Origins And Chemical Identification Of The Roasted From Raw Fructus Psoraleae, Junjun Yang, Jing Yang, Jie Du, Benjamin Feng, Xin Chai, Mingming Xiao, Yuefei Wang, Xiumei Gao

Peer Reviewed Articles

Fructus Psoraleae, a traditional Chinese medicine, is widely used for preventing and treating various diseases such as vitiligo, osteoporosis and psoriasis. Coumarin, such as psoralenoside, isopsoralenoside, psoralen and isopsoralen, are important compounds in Fructus Psoraleae. In our study, ultra performance liquid chromatography coupled with diode array detector was employed for an excellent method validation for simultaneous quantification of psoralenoside, isopsoralenoside, psoralen and isopsoralen, which was further applied in performing general survey of Fructus Psoraleae from the different origins and chemical identification of the roasted from raw Fructus Psoraleae in the light of illuminating the transformed rule of psoralenoside and isopsoralenoside. …


Rhoa Gtpase Controls Yap-Mediated Ereg Signaling In Small Intestinal Stem Cell Maintenance, Ming Liu, Zheng Zhang, Leesa Sampson, Xuan Zhou, Kodandaramireddy Nalapareddy, Benjamin Feng, Shailaja Akunuru, Jaime Melendez, Ashley Kuenzi Davis, Feng Bi, Hartmut Geiger, Mei Xin, Yi Zheng Nov 2017

Rhoa Gtpase Controls Yap-Mediated Ereg Signaling In Small Intestinal Stem Cell Maintenance, Ming Liu, Zheng Zhang, Leesa Sampson, Xuan Zhou, Kodandaramireddy Nalapareddy, Benjamin Feng, Shailaja Akunuru, Jaime Melendez, Ashley Kuenzi Davis, Feng Bi, Hartmut Geiger, Mei Xin, Yi Zheng

Peer Reviewed Articles

RHOA, a founding member of the Rho GTPase family, is critical for actomyosin dynamics, polarity, and morphogenesis in response to developmental cues, mechanical stress, and inflammation. In murine small intestinal epithelium, inducible RHOA deletion causes a loss of epithelial polarity, with disrupted villi and crypt organization. In the intestinal crypts, RHOA deficiency results in reduced cell proliferation, increased apoptosis, and a loss of intestinal stem cells (ISCs) that mimic effects of radiation damage. Mechanistically, RHOA loss reduces YAP signaling of the Hippo pathway and affects YAP effector epiregulin (EREG) expression in the crypts. Expression of an active YAP (S112A) mutant …


Fibroblast-Specific Tgf-Β–Smad2/3 Signaling Underlies Cardiac Fibrosis, Hadi Khalil, Onur Kanisicak, Vikram Prasad, Robert N. Correll, Xing Fu, Tobias Schips, Ronald J. Vagnozzi, Ruijie Liu, Thanh Huynh, Se-Jin Lee, Jason Karch, Jeffery D. Molkentin Sep 2017

Fibroblast-Specific Tgf-Β–Smad2/3 Signaling Underlies Cardiac Fibrosis, Hadi Khalil, Onur Kanisicak, Vikram Prasad, Robert N. Correll, Xing Fu, Tobias Schips, Ronald J. Vagnozzi, Ruijie Liu, Thanh Huynh, Se-Jin Lee, Jason Karch, Jeffery D. Molkentin

Peer Reviewed Articles

The master cytokine TGF-β mediates tissue fibrosis associated with inflammation and tissue injury. TGF-β induces fibroblast activation and differentiation into myofibroblasts that secrete extracellular matrix proteins. Canonical TGF-β signaling mobilizes Smad2 and Smad3 transcription factors that control fibrosis by promoting gene expression. However, the importance of TGF-β–Smad2/3 signaling in fibroblast-mediated cardiac fibrosis has not been directly evaluated in vivo. Here, we examined pressure overload–induced cardiac fibrosis in fibroblast- and myofibroblast-specific inducible Cre-expressing mouse lines with selective deletion of the TGF-β receptors Tgfbr1/2, Smad2, or Smad3. Fibroblast-specific deletion of Tgfbr1/2 or Smad3, but not Smad2, markedly …


Retrotransposons Are The Major Contributors To The Expansion Of The Drosophila Ananassae Muller F Element, Wilson Leung, Martin G. Burg, Spencer M. Batten, Lindsay M. Corbeill, Erica Enoch, Jesse J. Ensign, Mary E. Franks, Breanna Haiker, Judith A. Ingles, Lyndsay D. Kirkland, Josha M. Lorenz-Guertin, Jordan Matthews, Cody M. Mittig, Nicholaus Monsma, Katherine J. Olson, Guillermo Perez-Aragon, Alen Ramic, Jordan R. Ramirez, Christopher Scheiber, Patrick A. Schneider, Devon E. Schultz, Matthew Simon, Eric Spencer, Adam C. Wernette, Maxine E. Wykle, Elizabeth Zavala-Arellano, Mitchell J. Mcdonald, Kristine Ostby, Peter Wendland Aug 2017

Retrotransposons Are The Major Contributors To The Expansion Of The Drosophila Ananassae Muller F Element, Wilson Leung, Martin G. Burg, Spencer M. Batten, Lindsay M. Corbeill, Erica Enoch, Jesse J. Ensign, Mary E. Franks, Breanna Haiker, Judith A. Ingles, Lyndsay D. Kirkland, Josha M. Lorenz-Guertin, Jordan Matthews, Cody M. Mittig, Nicholaus Monsma, Katherine J. Olson, Guillermo Perez-Aragon, Alen Ramic, Jordan R. Ramirez, Christopher Scheiber, Patrick A. Schneider, Devon E. Schultz, Matthew Simon, Eric Spencer, Adam C. Wernette, Maxine E. Wykle, Elizabeth Zavala-Arellano, Mitchell J. Mcdonald, Kristine Ostby, Peter Wendland

Peer Reviewed Articles

The discordance between genome size and the complexity of eukaryotes can partly be attributed to differences in repeat density. The Muller F element (∼5.2 Mb) is the smallest chromosome in Drosophila melanogaster, but it is substantially larger (>18.7 Mb) in D. ananassae. To identify the major contributors to the expansion of the F element and to assess their impact, we improved the genome sequence and annotated the genes in a 1.4-Mb region of the D. ananassae F element, and a 1.7-Mb region from the D element for comparison. We find that transposons (particularly LTR and LINE retrotransposons) …


Group B Streptococcus Induces Neutrophil Recruitment To Gestational Tissues And Elaboration Of Extracellular Traps And Nutritional Immunity, Visheh Kothary, Ryan S. Doster, Lisa M. Rogers, Leslie A. Kirk, Kelli L. Boyd, Joann Romano-Keeler, Kathryn Haley, Shannon D. Manning, David M. Aronoff, Jennifer A. Gaddy Feb 2017

Group B Streptococcus Induces Neutrophil Recruitment To Gestational Tissues And Elaboration Of Extracellular Traps And Nutritional Immunity, Visheh Kothary, Ryan S. Doster, Lisa M. Rogers, Leslie A. Kirk, Kelli L. Boyd, Joann Romano-Keeler, Kathryn Haley, Shannon D. Manning, David M. Aronoff, Jennifer A. Gaddy

Peer Reviewed Articles

Streptococcus agalactiae, or Group B Streptococcus (GBS), is a gram-positive bacterial pathogen associated with infection during pregnancy and is a major cause of morbidity and mortality in neonates. Infection of the extraplacental membranes surrounding the developing fetus, a condition known as chorioamnionitis, is characterized histopathologically by profound infiltration of polymorphonuclear cells (PMNs, neutrophils) and greatly increases the risk for preterm labor, stillbirth, or neonatal GBS infection. The advent of animal models of chorioamnionitis provides a powerful tool to study host-pathogen relationships in vivo and ex vivo. The purpose of this study was to evaluate the innate immune response …


Post-Transplantation Cyclophosphamide And Ixazomib Combination Rescues Mice Subjected To Experimental Graft-Versus-Host Disease And Is Superior To Either Agent Alone, Ahmad Samer Al-Homsi, Austin Goodyke, Michael Mclane, Sarah Abdel-Mageed, Kelli Cole, Marlee Muilenburg, Benjamin Feng Nov 2016

Post-Transplantation Cyclophosphamide And Ixazomib Combination Rescues Mice Subjected To Experimental Graft-Versus-Host Disease And Is Superior To Either Agent Alone, Ahmad Samer Al-Homsi, Austin Goodyke, Michael Mclane, Sarah Abdel-Mageed, Kelli Cole, Marlee Muilenburg, Benjamin Feng

Peer Reviewed Articles

Lapses in the prevention of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) warrant novel approaches. Such approaches include, among others, the use of post-transplantation cyclophosphamide (PTC) and proteasome inhibitors. Although PTC alone consistently produces low rates of chronic GVHD, the incidence of acute GVHD remains significant. Inversely, prolonged post-transplantation administration of proteasome inhibitors carries a risk of paradoxical aggravation of GVHD. We examined whether the combination of cyclophosphamide and ixazomib addresses the limitations of each of these agents when used alone to prevent GVHD in mice subjected to allogeneic HSCT across MHC barriers. We chose ixazomib, an …


A Mouse Model For Binge-Level Methamphetamine Use, Shkelzen Shabani, Sydney K. Houlton, Laura Hellmuth, Erika Mojica, John R K Mootz, Zhen Zhu, Cheryl Reed, Tamara J. Phillips Nov 2016

A Mouse Model For Binge-Level Methamphetamine Use, Shkelzen Shabani, Sydney K. Houlton, Laura Hellmuth, Erika Mojica, John R K Mootz, Zhen Zhu, Cheryl Reed, Tamara J. Phillips

Peer Reviewed Articles

Binge/crash cycles of methamphetamine (MA) use are frequently reported by individuals suffering from MA use disorders. A MA binge is self-reported as multiple daily doses that commonly accumulate to 800 mg/day (~10 mg/kg/day for a 170 pound human). A genetic animal model with a similar vulnerability to binge-level MA intake is missing. We used selectively bred MA high drinking (MAHDR) and low drinking (MALDR) mouse lines to determine whether several procedural variations would result in binge-level MA intake. Data were also collected in two progenitor populations of the MA drinking lines, the DBA/2J (D2) strain and the F2 cross of …