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Full-Text Articles in Medical Specialties

Life Stressors And Immune Aging: Protective Effects Of Cognitive Reappraisal, Rebecca G. Reed, Steven R. Presnell, Ahmad Al-Attar, Charles T. Lutz, Suzanne C. Segerstrom May 2023

Life Stressors And Immune Aging: Protective Effects Of Cognitive Reappraisal, Rebecca G. Reed, Steven R. Presnell, Ahmad Al-Attar, Charles T. Lutz, Suzanne C. Segerstrom

Markey Cancer Center Faculty Publications

Stressful life events may accelerate aspects of immune aging, but habitual use of an adaptive emotion regulation strategy, cognitive reappraisal, may attenuate these effects. This study examined whether cognitive reappraisal moderates the associations between life stressor frequency and stressor desirability on aspects of immune aging, including late-differentiated CD8+ T and natural killer (NK) cells and inflammatory markers (IL-6, TNF-α, and CRP), both between and within people in a longitudinal sample of 149 older adults (mean age = 77.8, range: 64–92 years). Participants reported stressful life events, use of cognitive reappraisal, and provided blood semiannually for up to 5 years to …


Single Fraction And Hypofractionated Radiation Cause Cochlear Damage, Hearing Loss, And Reduced Viability Of Merlin-Deficient Schwann Cells, Christine T. Dinh, Si Chen, Aida Nourbakhsh, Kyle Padgett, Perry Johnson, Stefania Goncalves, Olena Bracho, Esperanza Bas, Jorge Bohorquez, Paula V. Monje, Cristina Fernandez-Valle, Nagy Elsayyad, Xuezhong Liu, Scott M. Welford, Fred Telischi May 2023

Single Fraction And Hypofractionated Radiation Cause Cochlear Damage, Hearing Loss, And Reduced Viability Of Merlin-Deficient Schwann Cells, Christine T. Dinh, Si Chen, Aida Nourbakhsh, Kyle Padgett, Perry Johnson, Stefania Goncalves, Olena Bracho, Esperanza Bas, Jorge Bohorquez, Paula V. Monje, Cristina Fernandez-Valle, Nagy Elsayyad, Xuezhong Liu, Scott M. Welford, Fred Telischi

Markey Cancer Center Faculty Publications

Background: Vestibular schwannomas (VS) are benign intracranial tumors caused by loss of function of the merlin tumor suppressor. We tested three hypotheses related to radiation, hearing loss (HL), and VS cell survival: (1) radiation causes HL by injuring auditory hair cells (AHC), (2) fractionation reduces radiation-induced HL, and (3) single fraction and equivalent appropriately dosed multi-fractions are equally effective at controlling VS growth. We investigated the effects of single fraction and hypofractionated radiation on hearing thresholds in rats, cell death pathways in rat cochleae, and viability of human merlin-deficient Schwann cells (MD-SC). Methods: Adult rats received cochlear irradiation with single …


The Plod2/Succinate Axis Regulates The Epithelial–Mesenchymal Plasticity And Cancer Cell Stemness, Yuxin Tong, Yifei Qi, Gaofeng Xiong, Junyan Li, Timothy L. Scott, Jie Chen, Daheng He, Linzhang Li, Chi Wang, Andrew N. Lane, Ren Xu May 2023

The Plod2/Succinate Axis Regulates The Epithelial–Mesenchymal Plasticity And Cancer Cell Stemness, Yuxin Tong, Yifei Qi, Gaofeng Xiong, Junyan Li, Timothy L. Scott, Jie Chen, Daheng He, Linzhang Li, Chi Wang, Andrew N. Lane, Ren Xu

Markey Cancer Center Faculty Publications

Aberrant accumulation of succinate has been detected in many cancers. However, the cellular function and regulation of succinate in cancer progression is not completely understood. Using stable isotope-resolved metabolomics analysis, we showed that the epithelial mesenchymal transition (EMT) was associated with profound changes in metabolites, including elevation of cytoplasmic succinate levels. The treatment with cell-permeable succinate induced mesenchymal phenotypes in mammary epithelial cells and enhanced cancer cell stemness. Chromatin immunoprecipitation and sequence analysis showed that elevated cytoplasmic succinate levels were sufficient to reduce global 5-hydroxymethylcytosinene (5hmC) accumulation and induce transcriptional repression of EMT-related genes. We showed that expression of procollagen-lysine,2-oxoglutarate …


Piloting An Oral History Approach To Investigate Cancer Perspectives Among Residents Of Appalachian Kentucky, Courtney Martin, Lauren Hudson, Nathan L. Vanderford Apr 2023

Piloting An Oral History Approach To Investigate Cancer Perspectives Among Residents Of Appalachian Kentucky, Courtney Martin, Lauren Hudson, Nathan L. Vanderford

Journal of Appalachian Health

Introduction: Kentucky ranks first in the U.S. in overall cancer incidence and mortality rates. Areas of the state that fall within the Appalachian Region, along Kentucky’s eastern border, experience disproportionately high rates of cancer compared to non-Appalachian counties.

Purpose: This pilot study investigates whether oral history interviews can be used to understand perspectives on cancer among residents of Appalachian Kentucky.

Methods: In 2020, participants (n = 5) who identified as being from and/or having strong connections to Appalachian Kentucky were recruited to participate in this pilot study. Participants included individuals working in cancer-related fields, oncology professionals, and those with personal …


Factors Associated With Sun Protection Behaviors Among Childhood Cancer Survivors, Melissa Fluehr, Gary Kwok, Jerod L. Stapleton, Margaret Masterson, Katie A. Devine Apr 2023

Factors Associated With Sun Protection Behaviors Among Childhood Cancer Survivors, Melissa Fluehr, Gary Kwok, Jerod L. Stapleton, Margaret Masterson, Katie A. Devine

UK CARES Faculty Publications

Background: Childhood cancer survivors (CCS) are at increased risk of developing skin cancer. Engaging in sun-protective behaviors may ameliorate that risk, but prior work shows that survivors engage in suboptimal levels of sun-protective behaviors. Guided by the Health Belief Model (HBM), this study evaluated factors associated with sun-protective behavior among CCS.

Methods: This is a secondary analysis of a survey study of 94 adult survivors of childhood cancer recruited from a long-term follow-up clinic. Participants reported their sun protection habits, skin type/ sensitivity, barriers to sun protection, and perceived severity and susceptibility of getting skin cancer. Descriptive statistics were used …


The Importance Of Translationally Evaluating Steroid Hormone Contributions To Substance Use, Erin E. Maher, Ashley Strzelecki, Jessica J. Weafer, Cassandra D. Gipson Apr 2023

The Importance Of Translationally Evaluating Steroid Hormone Contributions To Substance Use, Erin E. Maher, Ashley Strzelecki, Jessica J. Weafer, Cassandra D. Gipson

Markey Cancer Center Faculty Publications

Clinically, women appear to be more susceptible to certain aspects of substance use disorders (SUDs). The steroid hormones 17β-estradiol (E2) and progesterone (Pg) have been linked to women-specific drug behaviors. Here, we review clinical and preclinical studies investigating how cycling ovarian hormones affect nicotine-, cocaine-, and opioid-related behaviors. We also highlight gaps in the literature regarding how synthetic steroid hormone use may influence drug-related behaviors. In addition, we explore how E2 and Pg are known to interact in brain reward pathways and provide evidence of how these interactions may influence drug-related behaviors. The synthesis of this review demonstrates the critical …


Angiotensinogen In Sex And Hypertension: New Insights From The Multi-Ethnic Study Of Atherosclerosis (Mesa), Alan Daugherty, Hong S. Lu, George L. Bakris Apr 2023

Angiotensinogen In Sex And Hypertension: New Insights From The Multi-Ethnic Study Of Atherosclerosis (Mesa), Alan Daugherty, Hong S. Lu, George L. Bakris

Saha Cardiovascular Research Center Faculty Publications

No abstract provided.


Post-Intensive Care Syndrome And Pulmonary Fibrosis In Patients Surviving Ards-Pneumonia Of Covid-19 And Non-Covid-19 Etiologies, Jamie L. Sturgill, Kirby Mayer, Anna G. Kalema, Kinjal Dave, Stephanie Mora, Alborz Kalantar, David J. Carter, Ashley A. Montgomery-Yates, Peter E. Morris Apr 2023

Post-Intensive Care Syndrome And Pulmonary Fibrosis In Patients Surviving Ards-Pneumonia Of Covid-19 And Non-Covid-19 Etiologies, Jamie L. Sturgill, Kirby Mayer, Anna G. Kalema, Kinjal Dave, Stephanie Mora, Alborz Kalantar, David J. Carter, Ashley A. Montgomery-Yates, Peter E. Morris

Markey Cancer Center Faculty Publications

The purpose was to examine patient‑centered outcomes and the occurrence of lung fibrotic changes on Chest computed tomography (CT) imaging following pneumonia‑related acute respiratory distress syndrome (ARDS). We sought to investigate outpatient clinic chest CT imaging in survivors of COVID19‑related ARDS and non‑COVID‑related ARDS, to determine group differences and explore relationships between lung fibrotic changes and functional outcomes. A retrospective practice analysis of electronic health records at an ICU Recovery Clinic in a tertiary academic medical center was performed in adult patients surviving ARDS due to COVID‑19 and non‑COVID etiologies. Ninety‑four patients with mean age 53 ± 13 and 51% …


A Kinome-Wide Crispr Screen Identifies Ck1Α As A Target To Overcome Enzalutamide Resistance Of Prostate Cancer, Jinghui Liu, Yue Zhao, Daheng He, Katelyn M. Jones, Shan Tang, Derek B. Allison, Yanquan Zhang, Jing Chen, Qiongsi Zhang, Xinyi Wang, Chaohao Li, Chi Wang, Lang Li, Xiaoqi Liu Apr 2023

A Kinome-Wide Crispr Screen Identifies Ck1Α As A Target To Overcome Enzalutamide Resistance Of Prostate Cancer, Jinghui Liu, Yue Zhao, Daheng He, Katelyn M. Jones, Shan Tang, Derek B. Allison, Yanquan Zhang, Jing Chen, Qiongsi Zhang, Xinyi Wang, Chaohao Li, Chi Wang, Lang Li, Xiaoqi Liu

Markey Cancer Center Faculty Publications

Enzalutamide (ENZA), a second-generation androgen receptor antagonist, has significantly increased progression-free and overall survival of patients with metastatic prostate cancer (PCa). However, resistance remains a prominent obstacle in treatment. Utilizing a kinome-wide CRISPR-Cas9 knockout screen, we identified casein kinase 1a (CK1a) as a therapeutic target to overcome ENZA resistance. Depletion or pharmacologic inhibition of CK1a enhanced ENZA efficacy in ENZA-resistant cells and patient-derived xenografts. Mechanistically, CK1a phosphorylates the serine residue S1270 and modulates the protein abundance of ataxia telangiectasia mutated (ATM), a primary initiator of DNA double-strand break (DSB)-response signaling, which is compromised in ENZA-resistant cells and patients. Inhibition of …


Emt-Activated Secretory And Endocytic Vesicular Trafficking Programs Underlie A Vulnerability To Pi4k2a Antagonism In Lung Cancer, Xiaochao Tan, Guan-Yu Xiao, Shike Wang, Lei Shi, Yanbin Zhao, Xin Liu, Jiang Yu, William K. Russell, Chad J. Creighton, Jonathan M. Kurie Apr 2023

Emt-Activated Secretory And Endocytic Vesicular Trafficking Programs Underlie A Vulnerability To Pi4k2a Antagonism In Lung Cancer, Xiaochao Tan, Guan-Yu Xiao, Shike Wang, Lei Shi, Yanbin Zhao, Xin Liu, Jiang Yu, William K. Russell, Chad J. Creighton, Jonathan M. Kurie

Markey Cancer Center Faculty Publications

Hypersecretory malignant cells underlie therapeutic resistance, metastasis, and poor clinical outcomes. However, the molecular basis for malignant hypersecretion remains obscure. Here, we showed that epithelial-mesenchymal transition (EMT) initiates exocytic and endocytic vesicular trafficking programs in lung cancer. The EMT-activating transcription factor zinc finger E-box–binding homeobox 1 (ZEB1) executed a PI4KIIIβ-to-PI4KIIα (PI4K2A) dependency switch that drove PI4P synthesis in the Golgi and endosomes. EMT enhanced the vulnerability of lung cancer cells to PI4K2A small- molecule antagonists. PI4K2A formed a MYOIIA-containing protein complex that facilitated secretory vesicle biogenesis in the Golgi, thereby establishing a hypersecretory state involving osteopontin (SPP1) and other prometastatic …


Identification Of A Nacc1-Regulated Gene Signature Implicated In The Features Of Triple-Negative Breast Cancer, Chrispus Ngule, Hami Hemati, Xingcong Ren, Oluwafunminiyi Obaleye, Amos O. Akinyemi, Felix Oyelami, Xiaofang Xiong, Jianxun Song, Xia Liu, Jin-Ming Yang Apr 2023

Identification Of A Nacc1-Regulated Gene Signature Implicated In The Features Of Triple-Negative Breast Cancer, Chrispus Ngule, Hami Hemati, Xingcong Ren, Oluwafunminiyi Obaleye, Amos O. Akinyemi, Felix Oyelami, Xiaofang Xiong, Jianxun Song, Xia Liu, Jin-Ming Yang

Markey Cancer Center Faculty Publications

Triple-negative breast cancer (TNBC), characterized by a deficiency in estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor2 (HER2), is among the most lethal subtypes of breast cancer (BC). Nevertheless, the molecular determinants that contribute to its malignant phenotypes such as tumor heterogeneity and therapy resistance, remain elusive. In this study, we sought to identify the stemness-associated genes involved in TNBC progression. Using bioinformatics approaches, we found 55 up- and 9 downregulated genes in TNBC. Out of the 55 upregulated genes, a 5 gene-signature (CDK1, EZH2, CCNB1, CCNA2, and AURKA) involved in cell regeneration was positively correlated …


Leukocyte Tyrosine Kinase (Ltk) Is The Mendelian Determinant Of The Axolotl Melanoid Color Variant, Mirindi Kabangu, Raissa Cecil, Lloyd Strohl Ii, Nataliya Y. Timoshevskaya, Jeramiah James Smith, Stephen Randal Voss Apr 2023

Leukocyte Tyrosine Kinase (Ltk) Is The Mendelian Determinant Of The Axolotl Melanoid Color Variant, Mirindi Kabangu, Raissa Cecil, Lloyd Strohl Ii, Nataliya Y. Timoshevskaya, Jeramiah James Smith, Stephen Randal Voss

Markey Cancer Center Faculty Publications

The great diversity of color patterns observed among amphibians is largely explained by the differentiation of relatively few pigment cell types during development. Mexican axolotls present a variety of color phenotypes that span the continuum from leucistic to highly melanistic. The melanoid axolotl is a Mendelian variant characterized by large numbers of melanophores, proportionally fewer xanthophores, and no iridophores. Early studies of melanoid were influential in developing the single-origin hypothesis of pigment cell development, wherein it has been proposed that all three pigment cell types derive from a common progenitor cell, with pigment metabolites playing potential roles in directing the …


In Situ Microwave Fixation Provides An Instantaneous Snapshot Of The Brain Metabolome, Jelena A. Juras, Madison B. Webb, Lyndsay E. A. Young, Kia H. Markussen, Tara R. Hawkinson, Michael D. Buoncristiani, Kayli E. Bolton, Peyton T. Coburn, Meredith I. Williams, Lisa P. Y. Sun, William C. Sanders, Ronald C. Bruntz, Lindsey R. Conroy, Chi Wang, Matthew S. Gentry, Bret N. Smith, Ramon C. Sun Apr 2023

In Situ Microwave Fixation Provides An Instantaneous Snapshot Of The Brain Metabolome, Jelena A. Juras, Madison B. Webb, Lyndsay E. A. Young, Kia H. Markussen, Tara R. Hawkinson, Michael D. Buoncristiani, Kayli E. Bolton, Peyton T. Coburn, Meredith I. Williams, Lisa P. Y. Sun, William C. Sanders, Ronald C. Bruntz, Lindsey R. Conroy, Chi Wang, Matthew S. Gentry, Bret N. Smith, Ramon C. Sun

Markey Cancer Center Faculty Publications

Brain glucose metabolism is highly heterogeneous among brain regions and continues postmortem. In particular, we demonstrate exhaustion of glycogen and glucose and an increase in lactate production during conventional rapid brain resection and preservation by liquid nitrogen. In contrast, we show that these post- mortem changes are not observed with simultaneous animal sacrifice and in situ fixation with focused, high- power microwave. We further employ microwave fixation to define brain glucose metabolism in the mouse model of streptozotocin-induced type 1 diabetes. Using both total pool and isotope tracing analyses, we identified global glucose hypometabolism in multiple brain regions, evidenced by …


Targeting Lncrna Ddit4-As1 Sensitizes Triple Negative Breast Cancer To Chemotherapy Via Suppressing Of Autophagy, Ting Jiang, Jiaojiao Zhu, Shilong Jiang, Zonglin Chen, Ping Xu, Rong Gong, Changxin Zhong, Yueying Cheng, Xinyuan Sun, Wenjun Yi, Jinming Yang, Wenhu Zhou, Yan Cheng Apr 2023

Targeting Lncrna Ddit4-As1 Sensitizes Triple Negative Breast Cancer To Chemotherapy Via Suppressing Of Autophagy, Ting Jiang, Jiaojiao Zhu, Shilong Jiang, Zonglin Chen, Ping Xu, Rong Gong, Changxin Zhong, Yueying Cheng, Xinyuan Sun, Wenjun Yi, Jinming Yang, Wenhu Zhou, Yan Cheng

Markey Cancer Center Faculty Publications

In this study, it is found that the lncRNA, DNA damage inducible transcript 4 antisense RNA1 (DDIT4-AS1), is highly expressed in triple-negative breast cancer (TNBC) cell lines and tissues due to H3K27 acetylation in the promoter region, and promotes the proliferation, migration, and invasion of TNBC cells via activating autophagy. Mechanistically, it is shown that DDIT4-AS1 induces autophagy by stabilizing DDIT4 mRNA via recruiting the RNA binding protein AUF1 and promoting the interaction between DDIT4 mRNA and AUF1, thereby inhibiting mTOR signaling pathway. Furthermore, silencing of DDIT4-AS1 enhances the sensitivity of TNBC cells to chemotherapeutic agents such as paclitaxel both …


Impact Of In Utero Drug Exposure On Neonates Requiring Ecmo: A Retrospective Cohort Study, Hallie Walther, Aric Schadler, Karen Garlitz, John Anthony Bauer, Lindsay Kohler, Erika Waldsmith, Hubert O. Ballard Mar 2023

Impact Of In Utero Drug Exposure On Neonates Requiring Ecmo: A Retrospective Cohort Study, Hallie Walther, Aric Schadler, Karen Garlitz, John Anthony Bauer, Lindsay Kohler, Erika Waldsmith, Hubert O. Ballard

UK CARES Faculty Publications

The incidence of in utero drug exposure (IUDE) and neonatal extracorporeal membrane oxygenation (ECMO) utilization have both increased over the past decade. However, there are no studies to date that examine the impact that IUDE has on neonates requiring ECMO. In this retrospective cohort study, we compared the clinic course and outcomes of neonates who were placed on ECMO with IUDE vs. neonates without IUDE. Analysis included data extracted from medical records from all neonatal ECMO runs between January 2014 and January 2021 at the University of Kentucky Children’s Hospital. A total of 56 neonatal patients were placed on ECMO …


Association Of Symptoms And Mode Of Transportation To Emergency Department In Patients With Acute Coronary Syndrome, Leslie L. Davis, Thomas P. Mccoy, Barbara Riegel, Sharon Mckinley, Lynn V. Doering, Debra K. Moser Mar 2023

Association Of Symptoms And Mode Of Transportation To Emergency Department In Patients With Acute Coronary Syndrome, Leslie L. Davis, Thomas P. Mccoy, Barbara Riegel, Sharon Mckinley, Lynn V. Doering, Debra K. Moser

UK CARES Faculty Publications

Background: Patients with acute coronary syndrome (ACS) with symptoms matching their expectations of a heart attack are more likely to use emergency medical services (EMS) than not.

Objective: To determine whether presenting symptom clusters are associated with EMS use in ACS patients and if EMS use or symptom clusters are associated with prehospital delay.

Methods: This secondary analysis used data from the PROMOTION trial, a randomized clinical trial that enrolled 3522 subjects with a history of or at risk for ACS from 5 sites in the United States, Australia, and New Zealand. Subjects were randomized to usual care or an …


Body Mass Index Percentiles Versus Body Composition Assessments: Challenges For Disease Risk Classifications In Children, Jody L. Clasey, Elizabeth Ann Easley, Margaret O'Bryan Murphy, Stefan G. Kiessling, Arnold Stromberg, Aric Schadler, Hong Huang, John A. Bauer Mar 2023

Body Mass Index Percentiles Versus Body Composition Assessments: Challenges For Disease Risk Classifications In Children, Jody L. Clasey, Elizabeth Ann Easley, Margaret O'Bryan Murphy, Stefan G. Kiessling, Arnold Stromberg, Aric Schadler, Hong Huang, John A. Bauer

UK CARES Faculty Publications

Background: Identifying at-risk children with optimal specificity and sensitivity to allow for the appropriate intervention strategies to be implemented is crucial to improving the health and well-being of children. We determined relationships of body mass indexes for age and sex percentile (BMI%) classifications to actual body composition using validated and convenient methodologies and compared fat and non-fat mass estimates to normative cut-off reference values to determine guideline reliability. We hypothesized that we would achieve an improved ability to identify at-risk children using simple, non-invasive body composition and index measures.

Methods: Cross-sectional study of a volunteer convenience sample of 1,064 (537 …


Loss Of Peroxiredoxin Iv Protects Mice From Azoxymethane/Dextran Sulfate Sodium-Induced Colorectal Cancer Development, Pratik Thapa, Hong Jiang, Na Ding, Yanning Hao, Aziza Alshahrani, Eun Young Lee, Junichi Fujii, Qiou Wei Mar 2023

Loss Of Peroxiredoxin Iv Protects Mice From Azoxymethane/Dextran Sulfate Sodium-Induced Colorectal Cancer Development, Pratik Thapa, Hong Jiang, Na Ding, Yanning Hao, Aziza Alshahrani, Eun Young Lee, Junichi Fujii, Qiou Wei

Markey Cancer Center Faculty Publications

Peroxiredoxin IV (Prx4), a typical two-cysteine-containing member of the peroxidase family, functions as an antioxidant to maintain cellular redox homeostasis through the reduction of reactive oxygen species (ROS) via cycles of oxidation–reduction reactions. Under oxidative stress, all Prxs including Prx4 are inactivated as their catalytic cysteines undergo hyperoxidation, and hyperoxidized two-cysteine Prxs can be exclusively repaired and revitalized through the reduction cycle catalyzed by sulfiredoxin (Srx). Previously, we showed that Prx4 is a preferred substrate of Srx, and knockout of Srx in mice leads to resistance to azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colon carcinogenesis. To further understand the significance of the …


Exposure To Pcb126 During The Nursing Period Reversibly Impacts Early-Life Glucose Tolerance, Brittany Breon Rice, Keegan W. Sammons, Sara Y. Ngo Tenlep, Madeline T. Weltzer, Leryn J. Reynolds, Cetewayo S. Rashid, Hollie I. Swanson, Kevin J. Pearson Mar 2023

Exposure To Pcb126 During The Nursing Period Reversibly Impacts Early-Life Glucose Tolerance, Brittany Breon Rice, Keegan W. Sammons, Sara Y. Ngo Tenlep, Madeline T. Weltzer, Leryn J. Reynolds, Cetewayo S. Rashid, Hollie I. Swanson, Kevin J. Pearson

Markey Cancer Center Faculty Publications

Polychlorinated biphenyls (PCBs) are persistent environmental organic pollutants known to have detrimental health effects. Using a mouse model, we previously demonstrated that PCB126 exposure before and during pregnancy and throughout the perinatal period adversely affected offspring glucose tolerance and/or body composition profiles. The purpose of this study was to investigate the glucose tolerance and body composition of offspring born to dams exposed to PCB126 during the nursing period only. Female ICR mice were bred, and half of the dams were exposed to either vehicle (safflower oil) or 1 μmole PCB126 per kg of body weight via oral gavage on postnatal …


Latexin Regulates Sex Dimorphism In Hematopoiesis Via Gender-Specific Differential Expression Of Microrna 98-3p And Thrombospondin 1, Xiaojing Cui, Cuiping Zhang, Fang Wang, Xinghui Zhao, Shuxia Wang, Jinpeng Liu, Daheng He, Chi Wang, Feng-Chun Yang, Sheng Tong, Ying Liang Mar 2023

Latexin Regulates Sex Dimorphism In Hematopoiesis Via Gender-Specific Differential Expression Of Microrna 98-3p And Thrombospondin 1, Xiaojing Cui, Cuiping Zhang, Fang Wang, Xinghui Zhao, Shuxia Wang, Jinpeng Liu, Daheng He, Chi Wang, Feng-Chun Yang, Sheng Tong, Ying Liang

Markey Cancer Center Faculty Publications

Hematopoietic stem cells (HSCs) have the ability to self-renew and differentiate to all blood cell types. HSCs and their differentiated progeny show sex/gender differences. The fundamental mechanisms remain largely unexplored. We previously reported that latexin (Lxn) deletion increased HSC survival and repopulation capacity in female mice. Here, we find no differences in HSC function and hematopoiesis in Lxn knockout (Lxn-/- male mice under physiologic and myelosuppressive conditions. We further find that Thbs1, a downstream target gene of Lxn in female HSCs, is repressed in male HSCs. Male-specific high expression of micro- RNA 98-3p (miR98-3p) contributes to Thbs1 suppression in male …


Chronic Environmental Circadian Disruption Increases Atherosclerosis And Dyslipidemia In Female, But Not Male, Apolipoproteine-Deficient Mice, Jeffrey M. Chalfant, Deborah A. Howatt, Victoria B. Johnson, Lisa R. Tannock, Alan Daugherty, Julie S. Pendergast Mar 2023

Chronic Environmental Circadian Disruption Increases Atherosclerosis And Dyslipidemia In Female, But Not Male, Apolipoproteine-Deficient Mice, Jeffrey M. Chalfant, Deborah A. Howatt, Victoria B. Johnson, Lisa R. Tannock, Alan Daugherty, Julie S. Pendergast

Saha Cardiovascular Research Center Faculty Publications

Shift work chronically disrupts circadian rhythms and increases the risk of developing cardiovascular disease. However, the mechanisms linking shift work and cardiovascular disease are largely unknown. The goal of this study was to investigate the effects of chronically shifting the light-dark (LD) cycle, which models the disordered exposure to light that may occur during shift work, on atherosclerosis. Atherosclerosis is the progressive accumulation of lipid-filled lesions within the artery wall and is the leading cause of cardiovascular disease. We studied ApolipoproteinE-deficient (ApoE−/−) mice that are a well-established model of atherosclerosis. Male and female ApoE−/− mice were housed in control 12L:12D …


Cervical Spinal Cord Injury Leads To Injury And Altered Metabolism In The Lungs, Emily E. Huffman, Brittany E. Dong, Harrison A. Clarke, Lyndsay E. A. Young, Matthew S. Gentry, Derek B. Allison, Ramon C. Sun, Christopher M. Waters, Warren J. Alilain Mar 2023

Cervical Spinal Cord Injury Leads To Injury And Altered Metabolism In The Lungs, Emily E. Huffman, Brittany E. Dong, Harrison A. Clarke, Lyndsay E. A. Young, Matthew S. Gentry, Derek B. Allison, Ramon C. Sun, Christopher M. Waters, Warren J. Alilain

Saha Cardiovascular Research Center Faculty Publications

High-cervical spinal cord injury often disrupts respiratory motor pathways and disables breathing in the affected population. Moreover, cervically injured individuals are at risk for developing acute lung injury, which predicts substantial mortality rates. While the correlation between acute lung injury and spinal cord injury has been found in the clinical setting, the field lacks an animal model to interrogate the fundamental biology of this relationship. To begin to address this gap in knowledge, we performed an experimental cervical spinal cord injury (N = 18) alongside sham injury (N = 3) and naïve animals (N = 15) to assess lung injury …


Ferric Chloride-Induced Arterial Thrombosis And Sample Collection For 3d Electron Microscopy Analysis, Smita Joshi, Alexis N. Smith, Kanakanagavalli Shravani Prakhya, Hammodah Rawhi Hammodah Alfar, Joshua Lykins, Ming Zhang, Irina D. Pokrovskaya, Maria A. Aronova, Richard D. Leapman, Brian Storrie, Sidney W. Whiteheart Mar 2023

Ferric Chloride-Induced Arterial Thrombosis And Sample Collection For 3d Electron Microscopy Analysis, Smita Joshi, Alexis N. Smith, Kanakanagavalli Shravani Prakhya, Hammodah Rawhi Hammodah Alfar, Joshua Lykins, Ming Zhang, Irina D. Pokrovskaya, Maria A. Aronova, Richard D. Leapman, Brian Storrie, Sidney W. Whiteheart

Saha Cardiovascular Research Center Faculty Publications

Cardiovascular diseases are a leading cause of mortality and morbidity worldwide. Aberrant thrombosis is a common feature of systemic conditions like diabetes and obesity, and chronic inflammatory diseases like atherosclerosis, cancer, and autoimmune diseases. Upon vascular injury, usually the coagulation system, platelets, and endothelium act in an orchestrated manner to prevent bleeding by forming a clot at the site of the injury. Abnormalities in this process lead to either excessive bleeding or uncontrolled thrombosis/insufficient antithrombotic activity, which translates into vessel occlusion and its sequelae. The FeCl3-induced carotid injury model is a valuable tool in probing how thrombosis initiates and progresses …


An Improved Germline Genome Assembly For The Sea Lamprey Petromyzon Marinus Illuminates The Evolution Of Germline-Specific Chromosomes, Nataliya Timoshevskaya, Kaan İ. Eşkut, Vladimir A. Timoshevskiy, Sofia M.C. Robb, Carson Holt, Jon E. Hess, Hugo J. Parker, Cindy F. Baker, Allison K. Miller, Cody Saraceno, Mark Yandell, Robb Krumlauf, Shawn R. Narum, Ralph T. Lampman, Neil J. Gemmell, Jacquelyn Mountcastle, Bettina Haase, Jennifer R. Balacco, Giulio Formenti, Sarah Pelan, Ying Sims, Kerstin Howe, Olivier Fedrigo, Erich D. Jarvis, Jeramiah James Smith Mar 2023

An Improved Germline Genome Assembly For The Sea Lamprey Petromyzon Marinus Illuminates The Evolution Of Germline-Specific Chromosomes, Nataliya Timoshevskaya, Kaan İ. Eşkut, Vladimir A. Timoshevskiy, Sofia M.C. Robb, Carson Holt, Jon E. Hess, Hugo J. Parker, Cindy F. Baker, Allison K. Miller, Cody Saraceno, Mark Yandell, Robb Krumlauf, Shawn R. Narum, Ralph T. Lampman, Neil J. Gemmell, Jacquelyn Mountcastle, Bettina Haase, Jennifer R. Balacco, Giulio Formenti, Sarah Pelan, Ying Sims, Kerstin Howe, Olivier Fedrigo, Erich D. Jarvis, Jeramiah James Smith

Markey Cancer Center Faculty Publications

Programmed DNA loss is a gene silencing mechanism that is employed by several vertebrate and nonvertebrate lineages, including all living jawless vertebrates and songbirds. Reconstructing the evolution of somatically eliminated (germline-specific) sequences in these species has proven challenging due to a high content of repeats and gene duplications in eliminated sequences and a corresponding lack of highly accurate and contiguous assemblies for these regions. Here, we present an improved assembly of the sea lamprey (Petromyzon marinus) genome that was generated using recently standardized methods that increase the contiguity and accuracy of vertebrate genome assemblies. This assembly resolves highly contiguous, somatically …


Chalcone Derivative Cx258 Suppresses Colorectal Cancer Via Inhibiting The Top2a/Wnt/Β-Catenin Signaling, Xi Chen, Xiaocheng Lv, Lijie Gao, Jiawei Liu, Wei Wang, Lichao Guo, Mykhaylo S. Frasinyuk, Wen Zhang, David S. Watt, Chunming Liu, Xifu Liu Mar 2023

Chalcone Derivative Cx258 Suppresses Colorectal Cancer Via Inhibiting The Top2a/Wnt/Β-Catenin Signaling, Xi Chen, Xiaocheng Lv, Lijie Gao, Jiawei Liu, Wei Wang, Lichao Guo, Mykhaylo S. Frasinyuk, Wen Zhang, David S. Watt, Chunming Liu, Xifu Liu

Markey Cancer Center Faculty Publications

The deregulation in the Wnt/β-catenin signaling pathway is associated with many human cancers, particularly colorectal cancer (CRC) and, therefore, represents a promising target for drug development. We have screened over 300 semisynthetic and natural compounds using a Wnt reporter assay and identified a family of novel chalcone derivatives (CXs) that inhibited Wnt signaling and CRC cell proliferation. Among them, we selected CX258 for further in vitro and in vivo study to investigate the molecular mechanisms. We found that CX258 significantly inhibited β-catenin expression and nuclear translocation, inducing cell cycle arrest at the G2/M phase in CRC cells. Additionally, CX258 reduced …


Description Of Reaction And Vibrational Energetics Of Co2-Nh3interaction Using Quantum Computing Algorithms, Manh Tien Nguyen, Yueh-Lin Lee, Dominic Alfonso, Qing Shao, Yuhua Duan Mar 2023

Description Of Reaction And Vibrational Energetics Of Co2-Nh3interaction Using Quantum Computing Algorithms, Manh Tien Nguyen, Yueh-Lin Lee, Dominic Alfonso, Qing Shao, Yuhua Duan

Markey Cancer Center Faculty Publications

CO2 capture is critical to solving global warming. Amine-based solvents are extensively used to chemically absorb CO2. Thus, it is crucial to study the chemical absorption of CO2 by amine-based solvents to better understand and optimize CO2 capture processes. Here, we use quantum computing algorithms to quantify molecular vibrational energies and reaction pathways between CO2 and a simplified amine-based solvent model—NH3. Molecular vibrational properties are important to understanding kinetics of reactions. However, the molecule size correlates with the strength of anharmonicity effect on vibrational properties, which can be challenging to address using classical computing. Quantum computing can help enhance molecular …


Endogenous Glycoprotein Gpm6a Is Involved In Neurite Outgrowth In Rat Dorsal Root Ganglion Neurons, Gabriela I. Aparicio, Antonella León, Rocío Gutiérrez Fuster, Baylen Ravenscraft, Paula V. Monje, Camila Scorticati Mar 2023

Endogenous Glycoprotein Gpm6a Is Involved In Neurite Outgrowth In Rat Dorsal Root Ganglion Neurons, Gabriela I. Aparicio, Antonella León, Rocío Gutiérrez Fuster, Baylen Ravenscraft, Paula V. Monje, Camila Scorticati

Markey Cancer Center Faculty Publications

The peripheral nervous system (PNS) has a unique ability for self-repair. Dorsal root ganglion (DRG) neurons regulate the expression of different molecules, such as neurotrophins and their receptors, to promote axon regeneration after injury. However, the molecular players driving axonal regrowth need to be better defined. The membrane glycoprotein GPM6a has been described to contribute to neuronal development and structural plasticity in central-nervous-system neurons. Recent evidence indicates that GPM6a interacts with molecules from the PNS, although its role in DRG neurons remains unknown. Here, we characterized the expression of GPM6a in embryonic and adult DRGs by combining analysis of public …


Kegg_Pull: A Software Package For The Restful Access And Pulling From The Kyoto Encyclopedia Of Gene And Genomes, Erik D. Huckvale, Hunter N. B. Moseley Mar 2023

Kegg_Pull: A Software Package For The Restful Access And Pulling From The Kyoto Encyclopedia Of Gene And Genomes, Erik D. Huckvale, Hunter N. B. Moseley

Markey Cancer Center Faculty Publications

Background: The Kyoto Encyclopedia of Genes and Genomes (KEGG) provides organized genomic, biomolecular, and metabolic information and knowledge that is reasonably current and highly useful for a wide range of analyses and modeling. KEGG follows the principles of data stewardship to be findable, accessible, interoperable, and reusable (FAIR) by providing RESTful access to their database entries via their web-accessible KEGG API. However, the overall FAIRness of KEGG is often limited by the library and software package support available in a given programming language. While R library support for KEGG is fairly strong, Python library support has been lacking. Moreover, there …


Beliefs And Knowledge Related To Human Papillomavirus (Hpv) Vaccine Among African Americans And African Immigrants Young Adults, Adebola Adegboyega, Omoadoni Roseline Obielodan, Amanda T. Wiggins, Mark Dignan, Lovoria B. Williams Feb 2023

Beliefs And Knowledge Related To Human Papillomavirus (Hpv) Vaccine Among African Americans And African Immigrants Young Adults, Adebola Adegboyega, Omoadoni Roseline Obielodan, Amanda T. Wiggins, Mark Dignan, Lovoria B. Williams

UK CARES Faculty Publications

Background Despite the disparate human papillomavirus (HPV) infection rates among sexually active Black young adults, HPV vaccine uptake remains low among this population. This study aimed to explore HPV beliefs, attitudes, and knowledge among Black young adults and provide recommendations on ways to improve vaccine uptake.

Methods We used a mixed-method, convergent design to conduct five focus groups and administered a 40-item electronic survey that was developed with health belief model (HBM) constructs. We assessed HPV and vaccine knowledge, barriers, and attitudes toward vaccination. We analyzed quantitative data using descriptive statistics and bivariate methods. Focus group transcripts were analyzed using …


Novel Smad3 Variant Identified In A Patient With Familial Aortopathy Modeled Using A Zebrafish Embryo Assay, Mary Burchett Sheppard, Jeffrey D. Smith, Lisa L. Bergmann, Jakub Konrad Famulski Feb 2023

Novel Smad3 Variant Identified In A Patient With Familial Aortopathy Modeled Using A Zebrafish Embryo Assay, Mary Burchett Sheppard, Jeffrey D. Smith, Lisa L. Bergmann, Jakub Konrad Famulski

Saha Cardiovascular Research Center Faculty Publications

In human, pathogenic variants in smad3 are one cause of familial aortopathy. We describe a novel SMAD3 variant of unknown significance (VUS), V244F, in a patient who presented with aortic root dilation, right coronary artery ectasia, abdominal aortic aneurysm, right vertebral artery atresia, and cavernoma. Determination of variant pathogenicity impacted multiple aspects of the patient’s care, including the most appropriate surgical threshold for which to recommend a valve-sparing aortic root replacement. To determine whether the newly identified SMAD3 variant, and whether SMAD3 induced aortopathy in general, can be assayed in a zebrafish embryo model, we injected smad3a mRNA into Tg[kdrl:mCherry] …