Digital Commons Network^™

Methylome–Proteome Integration After Late-Life Voluntary Exercise Training Reveals Regulation And Target Information For Improved Skeletal Muscle Health, Toby L Chambers, Andrea Dimet-Wiley, Alexander R Keeble, Amin Haghani, Wen-Juo Lo, Gyumin Kang, Robert Brooke, Steve Horvath, Christopher S Fry, Stanley J Watowich, Yuan Wen, Kevin A Murach

Physiology Faculty Publications

Abstract: Exercise is a potent stimulus for combatting skeletal muscle ageing. To study the effects of exercise on muscle in a preclinical setting, we developed a combined endurance–resistance training stimulus for mice called progressive weighted wheel running (PoWeR). PoWeR improves molecular, biochemical, cellular and functional characteristics of skeletal muscle and promotes aspects of partial epigenetic reprogramming when performed late in life (22–24 months of age). In this investigation, we leveraged pan-mammalian DNA methylome arrays and tandem mass-spectrometry proteomics in skeletal muscle to provide detailed information on late-life PoWeR adaptations in female mice relative to age-matched sedentary controls (n = 7–10 …

Nonresolving Neuroinflammation Regulates Axon Regeneration In Chronic Spinal Cord Injury, Andrew N. Stewart, Christopher C. Bosse-Joseph, Reena Kumari, William M. Bailey, Kennedy A. Park, Victoria K. Slone, John C. Gensel

Physiology Faculty Publications

Chronic spinal cord injury (SCI) lesions retain increased densities of microglia and macrophages. In acute SCI, macrophages induce growth cone collapse and facilitate axon retraction away from lesion boundaries. Little is known about the role of sustained inflammation in chronic SCI or whether chronic inflammation affects regeneration. We used the colony-stimulating factor-1 receptor inhibitor, PLX-5622, to deplete microglia and macrophages months after complete crush SCI in female mice. Transcriptional analyses revealed a significant inflammatory depletion within chronic SCI lesions after PLX-5622 treatment. Both transcriptional analyses and immunohistochemistry revealed that Iba1⁺ cells repopulate to predepleted densities after treatment removal. Neuronal-enriched …

Programmable Scanning Diffuse Speckle Contrast Imaging Of Cerebral Blood Flow, Faezeh Akbari, Xuhui Liu, Fatemeh Hamedi, Mehrana Mohtasebi, Li Chen, Lei Chen, Guoqiang Yu

Physiology Faculty Publications

Significance: Cerebral blood flow (CBF) imaging is crucial for diagnosing cerebrovascular diseases. However, existing large neuroimaging techniques with high cost, low sampling rate, and poor mobility make them unsuitable for continuous and longitudinal CBF monitoring at the bedside. Aim: We aimed to develop a low-cost, portable, programmable scanning diffuse speckle contrast imaging (PS-DSCI) technology for fast, high-density, and depth-sensitive imaging of CBF in rodents. Approach: The PS-DSCI employed a programmable digital micromirror device (DMD) for remote line-shaped laser (785 nm) scanning on tissue surface and synchronized a 2D camera for capturing boundary diffuse laser speckle contrasts. New algorithms were developed …

Racial And Rural Disparities In Financial Toxicity And Healthcare Transitions Among Adolescent And Young Adult Cancer Survivors In Kentucky, Jean S. Edward, Brent J. Shelton, Lauren Corum, Haafsah Fariduddin, Katie Brown, John A. D’Orazio, Kimberly D. Northrip

Physiology Faculty Publications

Introduction: Adolescent and young adult cancer survivors, especially racial/ethnic minorities and rural residents are particularly vulnerable to financial toxicity due to limited healthcare access, socioeconomic disparities, and cultural/language barriers. These social determinants of health compound financial hardship and contribute to poor healthcare transitions from pediatric to adult care, leading to worse outcomes and higher mortality rates. Methods: Our cross-sectional survey study examined racial (Black vs White) and geographic (rural vs urban) disparities in financial toxicity and healthcare transition outcomes among 260 adolescent and young adult cancer survivors through the Kentucky Cancer Registry. Survey data were collected on financial toxicity, healthcare …

Differential Effects Of Myosin Activators On Myocardial Contractile Function In Nonfailing And Failing Human Hearts, Joohee Choi, Patrick T. Wood, Joshua B. Holmes, Katherine L. Dominic, Cristobal G. Dos Remedios, Kenneth S. Campbell, Julian E. Stelzer

Physiology Faculty Publications

The second-generation myosin activator danicamtiv (DN) has shown improved function compared with the first-generation myosin activator omecamtiv mecarbil (OM) in nonfailing myocardium by enhancing cardiac force generation but attenuating slowed relaxation. However, whether the functional improvement with DN compared with OM persists in remodeled failing myocardium remains unknown. Therefore, this study aimed to investigate the differential contractile responses to myosin activators in nonfailing and failing myocardium. Mechanical measurements were performed in detergent-skinned myocardium isolated from donor and failing human hearts. Steady-state force, stretch activation responses and loaded shortening velocity were analyzed at submaximal [Ca2+] in the absence or presence of …

Alternate Quantification Approaches For Cold-Induced Vasodilation In Human Glabrous Skin, J. A. Stout, D. E. Gerow, P. C. Clegg, K. Metzler-Wilson, T. E. Wilson

Physiology Faculty Publications

Introduction: Cold-induced vasodilation (CIVD) is a counterintuitive focal increase in glabrous skin blood flow during cold exposure with unclear local and neural mechanisms. Methods: We tested 12 (8 men, 4 women) healthy subjects’ laser-Doppler flux (LDF; just proximal to the nailbed) and arterial blood pressure (ABP) on a beat-by-beat basis. The experimental hand was exposed to warm (10 min 35°C) and then cold (30 min 8°C) water immersion and the contralateral control hand experienced 22°C–23°C air throughout. We analyzed beat-by-beat oscillations in LDF and ABP via a fast-Fourier transform (FFT) and transfer function analysis (TFA) of LDF to ABP. Results: …

Gastrocnemius Myofiber Type And Mitochondrial Alterations Associated With Peripheral Artery Disease Severity, Kate Kosmac, Rena Dana Wang, Jada Stewart, Parminder Kaur, Ahmed Ismaeel, Haseeb Ahsan, Lisa Hartnell, Esther E. Dupont-Versteegden, Mary M. Mcdermott, Robert L. Sufit, Luigi Ferrucci, Charlotte A. Peterson

Physiology Faculty Publications

The extent of walking impairment varies among individuals with peripheral artery disease (PAD), which may reflect differences in the adaptability of lower extremity muscles to ischemia-reperfusion injury characteristic of the disease. Analyses of gastrocnemius muscle biopsies from 113 individuals with PAD [mean ankle-brachial index (ABI) = 0.65 ± 0.13, 38 (33.6%) women, 76 (67.2%) Black] showed a wide range of myofiber type distributions (9.6%-82.6% type 1 myofibers). The abundance of oxidative type 1 myofibers negatively correlated with ABI (r = −0.22, P = 0.02), a measure of PAD severity. The abundance of type 1 myofibers also negatively correlated to 2a/x …

Inter-Rater Reliability Of Muscle Ultrasonography Performed By Multidisciplinary Novice Sonographers In The Evaluation Of Critically Ill Patients With Acute Kidney Injury Requiring Continuous Kidney Replacement Therapy, Felipe González-Seguel, Vinh Q. Tran, Chaitanya Anil Pal, Zan T. Shareef, Hayley P. Israel, Arimitsu Horikawa-Strakovsky, Yuan Wen, Benjamin R. Griffin, Javier A. Neyra, J. Pedro Teixeira, Kirby P. Mayer

Physiology Faculty Publications

Early diagnosis of muscle wasting in critically ill patients with acute kidney injury requiring continuous kidney replacement therapy (AKI-CKRT) may improve outcomes via timely rehabilitation and nutrition. Muscle ultrasound (MUS) has recently gained traction for assessing muscle atrophy in the intensive care unit (ICU) but requires training to achieve reproducibility. We evaluated the inter-rater reliability of MUS in patients with AKI-CKRT performed by multidisciplinary raters including nephrologists. Two blinded independent raters used portable ultrasound to acquire images of the rectus femoris (RF). All raters were clinicians routinely caring for patients with CKRT in the ICU and were initially novices in …

Sex-Based Differences In The Long-Term Fate Of Hippocampal Neurons Born After A Traumatic Brain Injury, Hannah C. Downing, Ashley B. Glover, Jessica E. Gebhardt, Katherine L. Thompson, Kathryn E. Saatman

Physiology Faculty Publications

Introduction: Moderate-to-severe traumatic brain injury (TBI) results in an early loss of immature hippocampal granule cells and the activation of typically quiescent neural stem cells (NSCs) in the dentate gyrus. Activation of NSCs leads to a robust increase in proliferation and generation of neural progenitor cells (NPCs), supporting restoration of the immature neuron population of over a period of 1–2 weeks. However, it is unclear if neurons born early after injury develop normally, survive long-term and functionally integrate into the hippocampal network. Although adult hippocampal neurogenesis is regulated in a sex-dependent manner, the majority of pre-clinical TBI studies lack the …

Skeletal Muscle Stem Cell Mitochondria Are Transferred To Muscle Fibers In Response To A Hypertrophic Stimulus, Jensen Goh, Julia G. Williams, Sarah E. Ogle, Jai K. Joshi, Logan N. Scott, Benjamin Burke, Alex R. Keeble, Nicholas T. Thomas, Christopher S. Fry, Ahmed Ismaeel, John J. Mccarthy

Physiology Faculty Publications

The fusion of skeletal muscle stem cell (MuSC) to myofibers during hypertrophy has exclusively focused on the transfer of the MuSC nucleus, leaving the fate of other MuSC organelles, such as mitochondria, largely unexplored. The objective of this study was to determine whether MuSCs transfer their mitochondria upon myofiber fusion in response to a hypertrophic stimulus. To achieve this goal, we specifically labeled MuSC mitochondria with Dendra2 fluorescence by crossing the MuSC-specific CreER (Pax7^CreER/CreER) mouse with the Rosa26-Dendra2 mouse to generate the Pax7-Dendra2 mouse. To induce the fusion of MuSC to myofibers, Pax7-Dendra2 mice underwent synergist ablation surgery …

Cognitive Rehabilitation Of Brain Tumor Survivors: A Systematic Review, Rabeet Tariq, Hafiza Fatima Aziz, Shahier Paracha, Nida Zahid, Timothy J. Ainger, Farhan A. Mirza, Syed Ather Enam

Neurology Faculty Publications

Background Cognitive decline is commonly seen in brain tumor (BT) patients and is associated with a worsened prognosis. Cognitive rehabilitation (CR) for cancer-related cognitive dysfunction has been widely studied for non-central nervous system cancers; however, recent emerging research has commenced documenting CR strategies for BT patients and survivors. Our objective was to review the current literature on various CR modalities in patients and BT survivors.

Methods The review was conducted in accordance with the PRISMA guidelines. The studies on CR were searched across 3 databases using a predefined search strategy. After removing duplicates, performing initial and full-text screenings, and applying …

Investigating The Psychometric Properties Of A Set Of Local Stem Literacy Instruments In Rasch Model, Lijun Shen

Theses and Dissertations--Educational Policy Studies and Evaluation

This study investigates the psychometric features of the See Blue STEM literacy inventories (SBSTEMs, including the elementary version SB-E and the middle school version SB-M) to determine their validity in measuring STEM literacy. Using data from elementary and middle school students participating in the See Blue STEM camp in 2019 and 2021-22, this research employed the Rasch Partial Credit Model (PCM) to analyze item-level performance and identify DIF items across various demographic subgroups (race, gender, free-lunch status, and potential first-generation status) and camp delivery modes (online versus in-person). Results indicated that both the elementary (SB-E) and middle school (SB-M) versions …

“Always Looking Over Your Shoulder”: College Students' Experiences With Codes Of Conduct At Evangelical Colleges & Universities, Kayla B. Powell

Theses and Dissertations--Educational Policy Studies and Evaluation

This qualitative research study investigated the experiences of college students enrolled at evangelical institutions that are affiliated with the Council for Christian Colleges & Universities (CCCU) and require students to follow an extensive code of conduct. These codes extend beyond academic expectations and mandate behavior in all aspects of daily life. Students who fail to comply are subject to a range of punishments as severe as expulsion. Sixteen traditional-aged undergraduate students from across the U.S. participated in semi-structured interviews that were analyzed using thematic analysis. Students described varied personal convictions regarding the rules; some earnestly strove to obey their campus …

A Unionid Mussel Biodiversity Hotspot Experiencing Unexplained Declines: Evaluating The Influence Of Chemical Stressors Using Caged Juveniles, W. Aaron Wilson, Christine Bergeron, Jennifer Archambault, Jason M. Unrine, Jess Jones, Braven Beaty, Damian Shea, Peter R. Lazaro, Jody L. Callihan, Jennifer J. Rogers

Plant and Soil Sciences Faculty Publications

Unionid mussel populations in a section of the Clinch River in Virginia, USA, has declined substantially, but the causes of the decline remain unknown. To investigate this zone of decline (ZOD), we deployed juvenile freshwater mussels (Villosa iris in 2012 and Lampsilis fasciola in 2013) in both cages and silos at sites within the Clinch River System. We analyzed mussel tissues for trace element and organic contaminant concentrations, shells for trace elements, and environmental media (total water, dissolved water, particulate sediment, and bedload sediment) for both inorganic and organic contaminants. We found a few differences between mussels deployed in cages …

Breaking Ground On Self-Efficacy: A Qualitative Exploration Of Intimate Partner Violence Survivors’ Experiences With Therapeutic Horticulture, Rachel Marie Reeves

Theses and Dissertations--Sociology

This dissertation explores how participation in a Therapeutic Horticulture program may support the self-efficacy of survivors of Intimate Partner Violence. Through a thematic analysis of interviews with 45 women living at a domestic violence shelter in Lexington, Kentucky, this study investigates whether and how gardening activities contributed to participants’ belief in their abilities to shape outcomes in their lives.

Findings are organized around Bandura’s four sources of self-efficacy: enactive mastery experiences, vicarious experience, verbal persuasion, and physiological/affective states. These insights contribute to feminist criminology and trauma-informed care literature by illuminating the transformative potential of nature-assisted healing programs.

Emplacing Deaths Of Despair Within The Rural Mortality Penalty: The Spatial Inequality Of Violent Death Across Rural America, Cameron A. Mcalister

Theses and Dissertations--Sociology

American life expectancy continues to diverge from most developed nations. Literature spanning several fields of scholarship has documented an uneven distribution of life expectancy between social groups and across geographic contexts. Frameworks such as “Deaths of Despair” and the rural mortality penalty describe the declining health trends among working class whites and rural America. But, conceptual development around these frameworks is still limited. This dissertation utilizes a rural sociological approach to bridging the gap between the Deaths of Despair framework and the rural mortality penalty by examining violent death patterns across diverse rural contexts. In doing so, I incorporate several …

The Research Examining Factors Associated With The Opioid Crisis Among Urban Adults (Refocus), Mona K.M. Goggins, Paige Orphé, Jovonna Atkinson, Brittany Miller-Roenigk, Kaylee A. Palomino, Danelle Stevens-Watkins

Educational, School, and Counseling Psychology Faculty Publications

Introduction: Deaths due to opioid-related overdoses have increased across the United States. Specifically in the state of Kentucky, African Americans are the only population that continues to experience an increase in opioid-related deaths. Previous literature highlights African Americans having unique drug use patterns due to systematic barriers and how these barriers limit access to protective factors and substance use treatment. The current study aims to specify patterns of African American non-medical prescription opioid use (NMPOU) and how these patterns may differ based on biological sex and generational cohort. Also, this study plans on using this data on patterns to inform …

Navigating Access To Pre-Exposure Prophylaxis (Prep), Carlos C. Mahaffey, Rohan D. Jeremiah, Andrew M. O’Neil, Déjà N. Clement, Isabel Cava, Fracisco R. Ruiz, Randolph D. Hubach, Danelle Stevens-Watkins

Educational, School, and Counseling Psychology Faculty Publications

Pre-exposure prophylaxis (PrEP) has contributed significantly to stabilizing HIV incidence rates across most populations. However, significant disparities in HIV incidence and PrEP uptake persist among Black men who have sex with men (BMSM). This study delved into the individual, sociocultural, and structural factors associated with PrEP access and uptake among 28 BMSM residing in designated HIV hotspots. Participants were recruited from communities identified as “high priority” by the US Department of Health and Human Services’ Ending the HIV Epidemic in the US initiative. Participants completed semi-structured interviews focusing on PrEP awareness, access, and barriers to uptake. Guided by the Socioecological …

Mental Health And Treatment Use In Undergraduate Engineering Students, Matthew D. Whitwer, Sarah A. Wilson, Joseph H. Hammer, Brenna Gomer

Educational, School, and Counseling Psychology Faculty Publications

Background: Engineering students experience high levels of distress and low rates of mental health treatment seeking, yet there is a gap in knowledge around how this compares with that of students in other fields of study. Given the influence of social identity (e.g., gender identity, race/ethnicity) on mental health and treatment seeking, it is important to account for sociodemographic variation across fields when performing such comparisons. Purpose: This study used Andersen's Behavioral Model to compare mental health distress and treatment use between students in engineering and other fields while controlling for sociodemographic factors. Methods: Survey data came from the 2021–2022 …

The Role Of Metabolic Gate Keepers In Cell Fate Decision Making, Brian Kelly

Theses and Dissertations--Biology

Maintaining cellular energy balance and redox stability is crucial to cell survival, with glutamine metabolism playing a central role. While extensively studied in cancer, where it supports biosynthesis and reduces oxidative stress to promote tumor growth, its function in non-cancerous contexts like tissue development and muscle regeneration remains less understood. A key aspect of stem cell biology is quiescence, a metabolically dormant state that preserves the stem cell pool, yet the mechanisms regulating this state are not fully clear. Here, we identify glutamine metabolism as a critical factor governing myoblast proliferation and quiescence through a metabolic program distinct from that …

Tam Receptors Mediate The Fpr2-Driven Pain Resolution And Fibrinolysis After Nerve Injury, Beate Hartmannsberger, Adel Ben‑Kraiem, Sofia Kramer, Carolina Guidolin, Ida Kazerani, Kathrin Doppler, Dominique Thomas, Robert Gurke, Marco Sisignano, Pranav P. Kalelkar, Andrés J. García, Paula V. Monje, Michael Sammeth, Asma Nusrat, Alexander Brack, Susanne M. Krug, Claudia Sommer, Heike L. Rittner

Markey Cancer Center Faculty Publications

Nerve injury causes neuropathic pain and multilevel nerve barrier disruption. Nerve barriers consist of perineurial, endothe- lial and myelin barriers. So far, it is unclear whether resealing nerve barriers fosters pain resolution and recovery. To this end, we analysed the nerve barrier property portfolio, pain behaviour battery and lipidomics for precursors of specialized pro-resolving meditators (SPMs) and their receptors in chronic constriction injury of the rat sciatic nerve to identify tar- gets for pain resolution by resealing the selected nerve barriers. Of the three nerve barriers—perineurium, capillaries and myelin—only capillary tightness specifically against larger molecules, such as fibrinogen, recuperated with …

Extracellular Vesicles Released By All Patients Contain Hne-Adducted Proteins: Implications Of Collateral Damage, Jenni Ho, Suriyan Sukati, Tamara Taylor, Sherry Carter, Brittany Fuller, Amy Marmo, Caryn Sorge, John A. D'Orazio, D. Allan Butterfield, Subbarao Bondada, Heidi Weiss, Daret K. St. Clair, Luksana Chaiswing

Markey Cancer Center Faculty Publications

Off-target neuronal injury is a serious side-effect observed in cancer survivors. It has previously been shown that pediatric acute lymphoblastic leukemia (ALL) survivors have a decline in neurocognition compared to healthy age-matched counterparts. Elevated oxidative stress has been documented to be a mediator in off- target tissue damage in cancer survivors. Early detection of oxidative stress markers may provide an opportunity to prevent off-target tissue damage. Extracellular vesicles (EVs) have surfaced as a potential diagnostic tool due to molecular cargo they contain. We investigated the potential for EVs to be a sensitive indicator of oxidative stress and off-target tissue damage …

Engaging Nurses In Effective Cost Of Care Conversations To Address Cancer-Related Financial Toxicity: Results From An Exploratory Survey, Jean Edward, Amanda T. Wiggins, Louis G. Baser, Haafsah Fariduddin, Joanna F. Doran, Monica F. Bryant, John August D'Orazio, Kimberly D. Northrip

Markey Cancer Center Faculty Publications

Few evidence-based trainings exist on how to equip healthcare providers, particularly nurses, with the skills to engage in cost of care conversations with patients/caregivers to mitigate the impact of cancer-related financial toxicity. This study evaluated a pilot training developed in collaboration with Triage Cancer® to prepare oncology nurses to identify and assist patients/caregivers facing financial and/or legal barriers to care. Ten pediatric oncology nurses completed the training and pre/post-surveys on behaviors related to financial and legal need screening, frequency and comfort level of answering questions, knowledge, and behavior changes, along with training evaluation questions. At baseline, six nurses reported never …

Pharmacological Or Genetic Inhibition Of Ltcc Promotes Cardiomyocyte Proliferation Through Inhibition Of Calcineurin Activity, Lynn A. C. Devilée, Abou Bakr M. Salama, Jessica M. Miller, Janice D. Reid, Qinghui Ou, Nourhan M. Baraka, Kamal Abou Farraj, Madiha Jamal, Yibing Nong, Todd K. Rosengart, Douglas A. Andres, Jonathan Satin, Tamer M. A. Mohamed, James E. Hudson, Riham R. E. Abouleisa

Markey Cancer Center Faculty Publications

Cardiomyocytes (CMs) lost during ischemic cardiac injury cannot be replaced due to their limited proliferative capacity. Calcium is an important signal transducer that regulates key cellular processes, but its role in regulating CM proliferation is incompletely understood. Here we show a robust pathway for new calcium signaling-based cardiac regenerative strategies. A drug screen targeting proteins involved in CM calcium cycling in human embryonic stem cell-derived cardiac organoids (hCOs) revealed that only the inhibition of L-Type Calcium Channel (LTCC) induced the CM cell cycle. Furthermore, overexpression of Ras-related associated with Diabetes (RRAD), an endogenous inhibitor of LTCC, induced CM cell cycle …

The Adiponectin-Pparγ Axis In Hepatic Stellate Cells Regulates Liver Fibrosis, Shangang Zhao, Qingzhang Zhu, Wang-Hsin Lee, Jan-Bernd Funcke, Zhuzhen Zhang, May-Yun Wang, Qian Lin, Bianca Field, Xue-Nan Sun, Guannan Li, Mbolle Ekane, Toshiharu Onodera, Na Li, Yi Zhu, Christine M. Kusminski, Terry D. Hinds Jr., Philipp E. Scherer

Markey Cancer Center Faculty Publications

Hepatic stellate cells (HSCs) are key drivers of local fibrosis. Adiponectin, conventionally thought of as an adipokine, is also expressed in quiescent HSCs. However, the impact of its local expression on the progression of liver fibrosis remains unclear. We recently generated a transgenic mouse line (Lrat-rtTA) that expresses the doxycycline-responsive transcriptional activator rtTA under the control of the HSC-specific lecithin retinol acyltransferase (Lrat) promoter, which enables us to specifically and inducibly overexpress or eliminate genes in these cells. The inducible elimination of HSCs protects mice from methionine/choline-deficient (MCD) diet-induced liver fibrosis, confirming their causal involvement in fibrosis development. We generated …

Urobilin Derived From Bilirubin Bioconversion Binds Albumin And May Interfere With Bilirubin Interacting With Albumin: Implications For Disease Pathology, Kevin I. Williams, Priyanka Suryadevara, Chang-Guo Zhan, Terry D. Hinds Jr., Zachary A. Kipp

Markey Cancer Center Faculty Publications

Background/Objectives: Bilirubin is a hydrophobic molecule that binds the carrier protein albumin for transport through systemic circulation. Bilirubin is cleared from the body through the liver and excreted into the intestines, where the microbiota modifies the chemical structure, forming urobilin, which can be reabsorbed into circulation by the hepatic portal vein. Urobilin has no known function. It is also unknown whether urobilin binds albumin for transport in circulation. We hypothesized that because of the likeness of their chemical structures, urobilin would also bind albumin like bilirubin does. Methods: First, we used in silico docking to predict if urobilin would bind …

Heme Oxygenase, Biliverdin Reductase, And Bilirubin Pathways Regulate Oxidative Stress And Insulin Resistance: A Focus On Diabetes And Therapeutics, Wang-Hsin Lee, Zachary A. Kipp, Sally Pauss, Genesee J. Martinez, Evelyn A. Bates, Olufunto O. Badmus, David E. Stec, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Metabolic and insulin-resistant diseases, such as type 2 diabetes mellitus (T2DM), have become major health issues worldwide. The prevalence of insulin resistance in the general population ranges from 15.5% to 44.6%. Shockingly, the global T2DM population is anticipated to double by 2050 compared with 2021. Prior studies indicate that oxidative stress and inflammation are instrumental in causing insulin resistance and instigating metabolic diseases. Numerous methods and drugs have been designed to combat insulin resistance, including metformin, thiazolidinediones (TZDs), sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide 1 receptor agonists (GLP1RA), and dipeptidyl peptidase 4 inhibitors (DPP4i). Bilirubin is an antioxidant with …

Dissecting The Biophysical Mechanisms Of Oleate Hydratase Association With Membranes, William A. Lathram, Robert J. Neff, Ashley N. Zalla, James D. Brien, Vivekanandan Subramanian, Christopher D. Radka

Markey Cancer Center Faculty Publications

This study investigates the dynamics of oleate hydratase (OhyA), a bacterial flavoenzyme from Staphylococcus aureus, and its interactions with lipid membranes, focusing on the factors influencing membrane binding and oligomerization. OhyA catalyzes the hydration of unsaturated fatty acids, playing a key role in bacterial pathogenesis by neutralizing host antimicrobial fatty acids. OhyA binds the membrane bilayer to access membrane-embedded substrates for catalysis, and structural studies have revealed that OhyA forms oligomers on membrane surfaces, stabilized by both protein-protein and protein-lipid interactions. Using fluorescence correlation spectroscopy (FCS), we examined the effects of membrane curvature and lipid availability on OhyA binding to …

Advances In Magnetic Nanoparticles For Molecular Medicine, Xiaoyue Yang, Sarah E. Kubican, Zhongchao Yi, Sheng Tong

Markey Cancer Center Faculty Publications

Magnetic nanoparticles (MNPs) are highly versatile nanomaterials in nanomedicine, owing to their diverse magnetic properties, which can be tailored through variations in size, shape, composition, and exposure to inductive magnetic fields. Over four decades of research have led to the clinical approval or ongoing trials of several MNP formulations, fueling continued innovation. Beyond traditional applications in drug delivery, imaging, and cancer hyperthermia, MNPs have increasingly advanced into molecular medicine. Under external magnetic fields, MNPs can generate mechano- or thermal stimuli to modulate individual molecules or cells deep within tissue, offering precise, remote control of biological processes at cellular and molecular …

Mir-27a-3p Regulates Intestinal Cell Proliferation And Differentiation Through Wnt/Β-Catenin Signalling, Chang Li, Yuning Zhou, Yinping Jiang, Zhijie Yin, Heidi L. Weiss, Qingding Wang, B. Mark Evers

Markey Cancer Center Faculty Publications

Intestinal stem cells differentiate into absorptive enterocytes, characterised by increased brush border enzymes such as intestinal alkaline phosphatase (IAP), making up the majority (95%) of the terminally differentiated cells in the villus. Loss of integrity of the intestinal epithelium plays a key role in inflammatory diseases and gastrointestinal infection. Here, we show that the intestinal microRNA (miR)-27a-3p is an important regulator of intestinal epithelial cell proliferation and enterocyte differentiation. Repression of endogenous miR-27a-3p leads to increased enterocyte differentiation and decreased intestinal epithelial cell proliferation in mouse and human small intestinal organoids. Mechanistically, miR-27a-3p regulates intestinal cell differentiation and proliferation at …