Medicine and Health Sciences Commons^™

Impact Of Exercise In Patients With Pancreatic Cancer Across Different Treatment Phases: A Systematic Review, Linda Toniolo, Anita Borsati, Cristina Crespo-Garcia, Diana Giannarelli, Christian Ciurnelli, Gloria Adamoli, Lorenzo Belluomini, Ilaria Trestini, Daniela Tregnago, Federico Schena, Robert U. Newton, Salvatore Paiella, Roberto Salvia, Michele Milella, Sara Pilotto, Alice Avancini

Research outputs 2022 to 2026

Background: With a dismal prognosis of 8–10 % 5-year survival since diagnosis, pancreatic cancer remains one of the most aggressive oncological diseases. This work aimed to evaluate the effects of exercise medicine on safety and feasibility, physical fitness, body composition, patient-reported outcomes, and clinical outcomes across different treatment phases in patients with pancreatic cancer. Method: PubMed, Cochrane, and Scopus databases were systematically screened to identify single-arm studies and randomized/non-randomized controlled trials investigating a physical exercise intervention in patients with pancreatic cancer. The RoB 2 and ROBINS-I tools were used to evaluate study quality for randomized and non-randomized studies, respectively. Qualitative …

Cumulative Triglyceride-Glucose Index And Hypertension Risk: A Longitudinal Cohort Study, Zhaogui Wu, Dan Wu, Sichi Xu, Yan Borné, Yulong Lan, Shuohua Chen

Research outputs 2022 to 2026

Background: Prior research has established a positive association between the single-measured triglyceride-glucose (TyG) index and hypertension. Nevertheless, longitudinal studies addressing the enduring impact of TyG index on incident hypertension are lacking. This study sought to explore the association between cumulative TyG index (cum-TyG) and incident hypertension, especially obesity-related hypertension (ORHT). Methods: A total of 21,017 individuals [mean (SD) age: 48.5 ± 11.7 years, male (%): 14,544 (69.2)] without hypertension were recruited from the Kailuan Study. The cum-TyG was determined by multiplying the mean TyG index by the time intervals between successive visits. Multivariable Cox regression models were used to investigate …

A Scoping Review Of Factors Influencing The Implementation Of Liquid Biopsy For Cancer Care, Samran Sheriff, Maree Saba, Romika Patel, Georgia Fisher, Tanja Schroeder, Gaston Arnolda, Dan Luo, Lydia Warburton, Elin Gray, Georgina Long, Jeffrey Braithwaite, Helen Rizos, Louise Ann Ellis

Research outputs 2022 to 2026

Background: Liquid biopsy (LB) offers a promising, minimally invasive alternative to traditional tissue biopsies in cancer care, enabling real-time monitoring and personalized treatment. Despite its potential, the routine implementation of LB in clinical practice faces significant challenges. This scoping review examines the barriers and facilitators influencing the implementation of liquid biopsies into standard cancer care. Methods: Four academic databases (PubMed, Scopus, Embase, and Web of Science) were systematically searched without language restrictions. We included peer-reviewed articles that were published between January 2019 and March 2024 that focused on the implementation of LB in cancer care or described barriers and facilitators …

Effects Of Short- And Long-Term Exercise Training On Cancer Cells In Vitro: Insights Into The Mechanistic Associations, Francesco Bettariga, Dennis R. Taaffe, Daniel A. Galvão, Robert U. Newton

Research outputs 2022 to 2026

Exercise is a therapeutic approach in cancer treatment, providing several benefits. Moreover, exercise is associated with a reduced risk for developing a range of cancers and for their recurrence, as well as with improving survival, even though the underlying mechanisms remain unclear. Preclinical and clinical evidence shows that the acute effects of a single exercise session can suppress the growth of various cancer cell lines in vitro. This suppression is potentially due to altered concentrations of hormones (e.g., insulin) and cytokines (e.g., tumor necrosis factor alpha and interleukin 6) after exercise. These factors, known to be involved in tumorigenesis, may …

Exercise Medicine As Adjunct Therapy During Radiation For Cancer Of The Prostate To Improve Treatment Efficacy – Protocol For The Eradicate Study: A Phase Ii Randomised Controlled Trial, Oliver Schumacher, Robert U. Newton, Colin Tang, Raphael Chee, Sjoerd B. Vos, Ronny S. Low, David Joseph, Dennis R. Taaffe, Daniel A. Galvão

Research outputs 2022 to 2026

Background: Tumour hypoxia resulting from inadequate perfusion is common in many solid tumours, including prostate cancer, and constitutes a major limiting factor in radiation therapy that contributes to treatment resistance. Emerging research in preclinical animal models indicates that exercise has the potential to enhance the efficacy of cancer treatment by modulating tumour perfusion and reducing hypoxia; however, evidence from randomised controlled trials is currently lacking. The ‘Exercise medicine as adjunct therapy during RADIation for CAncer of the prostaTE’ (ERADICATE) study is designed to investigate the impact of exercise on treatment response, tumour physiology, and adverse effects of treatment in prostate …

The Effect Of Prednisolone Ingestion And Acute Exercise On Lipocalin-2 And Its Variants In Young Men: A Pilot Randomised Crossover Study, Carlie Bauer, Rhiannon K. Patten, Qiyang Sun, Haoyun Li, Daniels Konja, Mary Woessner, Xuzhu Lin, Andrew Garnham, David L. Hare, Peter R. Ebeling, Marc Sim, Joshua R. Lewis, Yu Wang, Lewan Parker, Itamar Levinger

Research outputs 2022 to 2026

Lipocalin-2 (LCN2) has three main variants; polyaminated (hLCN2) and non-polyaminated (C87A and R81E). The polyaminated form is proposed to positively influence energy control, whereas the non-polyaminated forms negatively impact energy control in mice. Glucocorticoids negatively affect glucose regulation and exercise has a positive effect. We hypothesise that glucocorticoids will suppress, while exercise will increase hLCN2, and decrease C87A and R81E, which will be associated with improved insulin sensitivity. In a randomised crossover design, nine young healthy men (aged 27.8 ± 4.9 years; BMI 24.4 ± 2.4 kg/m2) completed 30 min of high-intensity aerobic exercise (90–95% heart rate reserve) after glucocorticoid …

Cognitive Frailty And Cardiometabolic Risk In Middle-Aged And Older Adults: Evidence From The Uk And China, Haiyang Yan, Jingjing Lang, Chengfeng Li, Samaneh Eftekhariranjbar, Guoyan Jiang, Jing Lei, Lixin Sun, Carlos J. Toro-Huamanchumo, Zhongyang Guan

Research outputs 2022 to 2026

Background: Cognitive frailty, a novel construct integrating cognitive and physical deficits, is increasingly recognized in aging research. Aims: This study aimed to examine the associations between cognitive frailty and cardiometabolic risk in two nationally representative cohorts from China and the United Kingdom. Methods: We analyzed data from 7,628 participants in the China Health and Retirement Longitudinal Study (CHARLS) and 4,703 participants from the English Longitudinal Study of Ageing (ELSA), all aged ≥ 50 years. Frailty was assessed using the frailty index (FI) in the main analysis. Cox proportional hazards models were applied to estimate hazard ratios (HRs) for incident cardiometabolic …

Periodizing Exercise Medicine Prescription For Patients With Cancer: A Narrative Opinion, Francesco Bettariga, Robert U. Newton, Chris Bishop, Luca Maestroni, Anita Borsati, Alice Avancini, Sara Pilotto, Dennis R. Taaffe, Daniel A. Galvão, G. Gregory Haff

Research outputs 2022 to 2026

Exercise has emerged as an effective therapeutic strategy in cancer management. Long-term supervised exercise programs, including resistance training and aerobic training, can improve body composition and physical fitness, modulate circulating factors (e.g., hormones, cytokines), enhance treatment tolerance, and reduce side effects, potentially influencing cancer progression and reducing mortality risk. Despite advancements in exercise oncology, opportunities remain to refine exercise prescription through the integration of advanced methodologies such as periodization and autoregulatory programming strategies. Periodization, a systematic approach to organizing training over time, has demonstrated benefits in general fitness and clinical populations but is underexplored in cancer care. Emerging evidence suggests …

Rac1 In Gastric Cancer: A Molecular Driver Of Invasion, Emt, And Therapeutic Resistance, Jianwen Li, Yahong Zhu, Ruifeng Duan, Yueli Tian, Xingang Li, Ying Song

Research outputs 2022 to 2026

Gastric cancer (GC) ranks as the fifth most common cancer worldwide and is the third main cause of cancer-related mortality, posing a substantial burden to global public health. Research suggests that targeted therapy and immunotherapy may become more effective treatment options for advanced, unresectable, or metastatic gastric cancer. Ras-related C3 botulinum toxin substrate 1 (Rac1), a small GTP-binding protein within the Rac subfamily of the Rho GTPase family, is a critical molecule that promotes cancer cell invasion and metastasis by regulating signal transmission and promoting cell polarity. It has emerged as a key driver of tumor development and metastasis in …

Cultural Adaptation Of An Innovative Reproductive Health Assessment Tool For Dementia Research In Africa: Insights From The Fember-Africa Study, Alice Moraa Ondieki, Anne Njogu, Cynthia I Sabel Smith, Edna Bosire, Karen Blackmon, Harrison Kaleli, Jasmit Shah, Rachel Maina, Sheila Waa, Chinedu Momoh

Brain and Mind Institute

Background: Dementia research accounts for only 0.1% of all research in Africa,making it the lowest among all low- and middle-income country (LMIC) regions. Thedevelopment and adaptation of biological and psychosocial measures in ethnicallyand culturally diverse populations remain limited but are essential for culturallyinformed research. This is particularly critical for examining sex- and gender-basedvulnerabilities to Alzheimer’s disease and related dementias (ADRD), including factorssuch as reproductive health and fertility.

Method: We conducted a thorough review of our clinical and health questionnaires forcultural relevance and sensitivity through a series (n = 3) of focus groups discussions.These focus groups included a diverse range of …

Objective Structured Clinical Examination (Osce) For Interscalene Brachial Plexus Block Utilizing Ultrasound Guidance And Landmark Technique, Madison Mize, Mckayla Moore, Peyton Shell

Doctoral Projects

The purpose of this doctoral project was to create learning and evaluation tools for interscalene brachial plexus blocks (ISBPB) to be used by certified registered nurse anesthetists (CRNAs) and students in the Nurse Anesthesia Program (NAP) at The University of Southern Mississippi (USM). ISBPB is a regional anesthesia technique used to provide anesthesia for procedures of the shoulder and upper arm. CRNAs and students can use these tools to refresh their current knowledge and enhance their regional anesthesia skills.

The objective structured clinical examination (OSCE) and cognitive aid for ISBPB utilizing landmark and ultrasound-guided techniques were evaluated by the USM …

Listening Beyond The Stethoscope, Lia M. Smerina, Priya Darbhanga

be Still

No abstract provided.

What The Stethoscope Can’T Hear: A Book Review Of Every Patient Tells A Story, Faith Abraham

be Still

My love for reading has always shaped the way I see people and stories. Through books, I’ve learned to listen deeply to characters, voices, and emotions. That same curiosity drives how I approach medicine and the humanities. Reading reminds me that every person carries a story worth understanding, and that healing often begins with paying attention.

Impact Of Structured Internal Medicine Pharmacotherapy Education In Improving Pharmacist Readiness In Transitioning To An Academic Medical Center, Jude Pierre, Erika Dittmar, Heidi Clarke, Radhan B. Gopalani, Stephanie Palma

Nursing & Health Sciences Research Journal

Introduction: Baptist Hospital of Miami (BHM) is transitioning to an academic medical center by starting medical residency training in July 2025. As healthcare systems expand, pharmacists must ensure safe medication dispensing and provide real-time clinical decision support. To support this transition, a structured internal medicine pharmacotherapy curriculum was developed to refresh clinical knowledge and enhance confidence among experienced clinical pharmacists.

Methods: A single-site, Institutional Review Board-exempt, quality improvement project was conducted at BHM. Inclusion criteria included Clinical Pharmacists 2s (primarily decentralized pharmacists with ≥ 1 year of pharmacy experience at BHM) who completed a structured pharmacotherapy curriculum from January 2025 …

A Retrospective Analysis Of Relapse Rates And Medication Compliance In Bipolar I And Bipolar Ii Disorders: A Comparative Study, Nasir Mehmood, Qudsia Tariq

Pakistan Journal of Neurological Sciences (PJNS)

Background and objective:

Bipolar disorder is a chronic, serious mental health condition characterized by mood episodes, and medication non-compliance is a significant predictor of relapse. The objective of this study was to investigate the relapse rates and medication compliance in patients with bipolar I and II disorders.

Methods:

This retrospective observational study was conducted at Karwan-e-Hayat Institute for Mental Health Care, Karachi, Pakistan. Medical records of 377 patients diagnosed with bipolar I or bipolar II disorder between July 2019 and June 2022 were retrieved from the Hospital Management System (HMS). Diagnosis was confirmed using DSM-IV criteria. Medication compliance was assessed …

The Revised Risk Analysis Index Outperforms The 5-Factor Modified Frailty Index In Predicting Postoperative Morbidity After Pilon Fracture Fixation., Gabriel Deoliveira, Amber Park, Arsalaan Sayyed, Aruni Areti, Nithin Gupta, Taylor Manes, Morgan Turnow, Benjamin Taylor, Jack W Weick

Trauma and Acute Care Articles

BACKGROUND: Pilon fractures often result from high energy mechanisms resulting in long-term morbidity and postoperative complications. While there is extensive literature investigating frailty scales as tools for preoperative risk stratification in orthopedic surgery, there is no literature regarding their use in fixation of pilon fractures. The objective of this study was to compare the predictive ability and discriminative accuracy of the Revised Risk Analysis Index (RAI-rev) and the 5-Item Modified Frailty (mFI-5) in 30-day postoperative outcomes following surgical fixation of pilon fractures.

METHODOLOGY: The ACS-NSQIP database was used to identify patients undergoing surgical fixation of pilon fractures from 2015 to …

Advancing Trypanosoma Cruzi N-Myristoyltransferase As A Drug Target For Chagas Disease Through In Silico Discovery And Biochemical Evaluation, Diana Citlali González García

Open Access Theses & Dissertations

Chagas disease remains one of the most persistent and neglected parasitic infections in the Americas, advancing silently through the intracellular replication of Trypanosoma cruzi amastigotes and the invasive spread of trypomastigotes. The survival of the parasite is critically reliant on protein N-myristoylation, a lipid modification catalyzed by N-myristoyltransferase (NMT). This dissertation aims to advance beyond prior studies by systematically investigating NMT inhibition across multiple biological levels, spanning from the characterization of the purified enzyme, through cellular infection models, to the global proteomic remodeling induced within the parasite, thereby evaluating TcNMT as a potential therapeutic vulnerability in T.cruzi.Recombinant TcNMT was expressed, …

Dual-Level Pattern Tree For Visual Field Improves Glaucoma Progression And Polygenic Risk Prediction, Luo Song, Lucy Q. Shen, Louis R. Pasquale, Michael V. Boland, Sarah R. Wellik, Carlos Gustavo De Moraes, Ayellet Segre, Janey L. Wiggs, Constance Turman, Jonathan S. Myers, Tobias Elze, Nazlee Zebardast, David S. Friedman, Jae H. Kang, Mengyu Wang

Wills Eye Hospital Papers

PURPOSE: To develop a dual-level pattern tree to characterize visual field (VF) loss subtypes that can be used to better predict glaucoma progression and glaucoma polygenic risk scores (PRSs).

METHODS: This study included 113,030 patients from three datasets, each used for a specific purpose: (1) model training, (2) progression forecasting, and (3) PRS correlations. We applied archetypal analysis to cluster 24-2 VFs into trunk patterns and their branch patterns. The Cox regression model was used to forecast VF progression using mean deviation (MD) slope, MD-fast slope, total deviation (TD) pointwise slope, and visual field index (VFI) slope. Multivariable regression analyses …

Net Effects Of Correlated Determinants Of Health Among U.S. Older Adults, Haomiao Jia, E I. Lubetkin

Publications and Research

Background

The health effect produced by a contributing factor alone may be different from the effect when other interacting factors are present. The effects of a set of contributors, estimated by regression coefficients, may be invalid or inappropriate if some of the predictors are correlated or the model has interaction and nonlinear terms. The net effect (NE) of a given contributing factor is the effect produced by the factor alone, not by other factors due to their correlations with the factor of interest. This study estimated NE of selected determinants of health for U.S. older adults.

Methods

Participants, aged ≥ …

Monte Carlo Simulations Of Geometric Deformation Of Harrison-Anderson-Mick Applicators Used In Intraoperative Radiation Therapy, Benjamin Insley, Brett Bocian, Sam Beddar, Reza Reiazi, Patrick James Jensen, Rachael M Martin-Paulpeter, Joshua Scott Niedzielski, David Flint, Gabriel Oliveira Sawakuchi, Luis Augusto Perles

Faculty, Staff and Student Publications

Background: The Harrison-Anderson-Mick (HAM) applicator is a high-dose-rate intraoperative radiotherapy (HDR-IORT) applicator used to position Ir-192 brachytherapy sources over surgically-accessed tumor volumes or post-resection tumor beds. Because of the lack of a 3D imaging system, dwell times are optimized pre-surgery by a TG-43-based treatment planning system (TPS) that assumes a perfectly flat applicator surface surrounded by an infinite water phantom. These assumed conditions are disparate from typical treatment conditions, especially in the pelvic regions, which often involve uneven patient surfaces and superficial irradiations with little to no backscatter material.

Purpose: Develop and validate a Monte Carlo (MC) model of HDR-IORT …

Endoscopic Retrograde Cholangiopancreatography And Primary Sclerosing Cholangitis: A Retrospective Study Of A High-Volume Program, Kristel Leung, Michael Youssef, Yasi Xiao, Catherine Streutker, Aliya Gulamhusein, Bettina Hansen, Natalia Calo, Gary May, Jeffrey Mosko, Gideon Hirschfield

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is valuable in management of primary sclerosing cholangitis (PSC). Herein, we characterize individuals with PSC who underwent ERCP on-demand at a high-volume quaternary centre, with evaluation of pathology results and short-term postprocedural outcomes.

METHODS: This retrospective cohort study evaluated patients with PSC who underwent ERCP at St Michael's Hospital between April 2011 and July 2021. Chart review was conducted to collect clinical, procedural, and pathology data, and reported post-ERCP complications within 90 days. Logistic regression analyses were conducted to evaluate factors associated with post-ERCP complications and placement of a biliary stent.

RESULTS: One hundred and …

Trends In Hospital Resource Use For Children With Complex Chronic Conditions., Nathaniel D. Bayer, Matthew Hall, Maria Osipovich, John M. Morrison, Christian D. Pulcini, Jana C. Leary, Joanna E. Thomson, Tamara D. Simon, Dennis Z. Kuo, Jeffrey D. Colvin, Eyal Cohen, Jay G. Berry

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Despite a small prevalence, children with complex chronic conditions (CCCs) use substantial inpatient resources.

OBJECTIVE: To assess national trends in hospital discharges, bed days, and hospital charges for children with and without CCCs in the US from 2000 to 2022.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, repeated cross-sectional study used hospital discharge data from the Kids' Inpatient Database (KID) from the years 2000, 2003, 2006, 2009, 2012, 2016, 2019, and 2022 for US children aged 0 to 18 years, excluding uncomplicated newborn discharges.

EXPOSURE: Presence of 0, 1, 2, or 3 or more CCCs.

MAIN OUTCOMES AND MEASURES: Trends …

Definition Of The 3d Position And Motion Status Of The Moving Heart Based On 2d Projections, Lawrence D. Orijuela

Electronic Theses, Projects, and Dissertations

This thesis presents a novel application of deep learning to the estimation of pulmonary vein coordinates using X-ray image pairs from a FORBILD Thorax phantom derived motion dataset. A Siamese neural network was developed to predict the 3D coordinates of one pulmonary vein at a time, specifically the Right Superior Pulmonary Vein (RSPV), Left Superior Pulmonary Vein (LSPV), Left Inferior Pulmonary Vein (LIPV), or Right Inferior Pulmonary Vein (RIPV), based on two-dimensional projection images.

The input data consisted of over 1.6 million grayscale X-ray image pairs across 1331 virtual patients, each annotated with ground truth 3D coordinates. To manage memory …

Comparative Value Of Echocardiography Vs. Right Heart Catheterization In Heart Failure With Preserved Ejection Fraction, Nathanael Tran, Mohammad Shaar, Hussein Al-Sudani, Ramy Sedhom, Hamza Akhtar, Kevin Bryan Lo, Gregg S. Pressman

Einstein Health Papers

BACKGROUND: Echocardiography and right heart catheterization (RHC) are useful in the evaluation of heart failure with preserved ejection fraction (HFpEF). We compared the two among decompensated HFpEF patients to determine their relative value in predicting all-cause mortality and a composite of cardiovascular (CV) death and heart failure (HF) readmission at 1 year.

METHODS: One hundred seventy-eight decompensated HFpEF patients who underwent both procedures and survived to hospital discharge were retrospectively identified. Hospital records and the National Death Index were queried to determine outcomes. Echocardiographic and invasive parameters were tested for significant associations with each outcome. Additionally, three predictive models were …

Do Patient-Important Outcomes Differ By Care Setting? Findings From Semi-Structured Interviews With Individuals With Diabetes, Amy Cunningham, Alexzandra Gentsch, Pouya Arefi, Judd E. Hollander, Marianna D Lanoue, Amanda M. B. Doty, Geoffrey Mills, Brendan Carr, Kristin L. Rising

Department of Emergency Medicine Faculty Papers

Background: Patient-important outcomes (PIOs) reflect patient values and preferences. Prior studies have elicited a variety of PIOs for diabetes. However, no studies have examined whether, or how, PIOs differ across diabetes care settings. The purpose of this study was to compare the frequencies of PIOs derived from patients with diabetes in primary care (PC), acute care (emergency department (ED)), and post-acute care (post-hospital discharge (PHD)) settings within a large delivery system. Methods: This study was an analysis of 89 interviews with patients in PC, ED, and PHD settings. Participants had moderately to poorly controlled diabetes, defined as follows: presented to …

Applying Entrustable Professional Activities Across Emergency Medicine Medical Education Fellowships: A Cross-Institutional Commentary, Carrie Maupin, Ambika Anand, Danielle Nesbit, Casey Morrone, Danielle Sultan

Department of Emergency Medicine Faculty Papers

No abstract provided.

Evaluation Of Heterotopic Ossification Following Two-Level Cervical Disc Arthroplasty With A Peek-On-Ceramic Artificial Disc, Jad Khalil, Hyan Bae, Pierce Nunley, K Brandon Strenge, Ashvin Patel, Armen Khachatryan, Rick Sasso, Andrew Park, Christopher Good, James Yue, Paul Kim, Richard Guyer

Conference Presentation Abstracts

Introduction: While favorable outcomes have consistently been reported following treatment of disc degeneration with cervical total disc replacement (cTDR), the development of heterotopic ossification (HO) at the index level has been reported. This study evaluated baseline characteristics potentially associated with the development of HO, as well as the impact of HO on 5-year clinical outcomes Materials and Methods: Baseline characteristics and 5-year outcomes of two-level polyetheretherketone (PEEK)-on-ceramic cTDR patients were stratified by worst HO grade at either index level through 5 years (defined as grade 1, 2, 3 or 4 on the McAfee/Mehren scale). Baseline index-level radiographic variables were stratified …

Predicting Five-Year Comorbid Bipolar Disorder After Attention-Deficit/Hyperactivity Disorder Diagnosis: A Population-Based Machine Learning Approach, Yen-Shan Yang, Chih-Wei Hsu, Liang-Jen Wang, Kuo-Chuan Hung, Yang-Chieh Brian Chen, Chih-Sung Liang, Mu-Hong Chen

Children’s Nutrition Research Center Staff Publications

Background

Early detection and accurate prediction of bipolar disorders (BDs) comorbidity in individuals with attention-deficit/hyperactivity disorder (ADHD) are clinically critical. This study used machine-learning methods to identify features predictive of subsequent BD among patients initially diagnosed with ADHD.

Methods

We analyzed claims from the Taiwan National Health Insurance Research Database (2000–2013) and included patients aged ≥ 12 years with at least two diagnoses of ADHD. Predictor features included demographics (sex, age at ADHD onset), healthcare utilization (psychiatric outpatient visit counts), comorbidities (International Classification of Diseases–coded diagnoses), psychiatric medications (Anatomical Therapeutic Chemical–coded prescriptions), and family psychiatric history. All features were extracted …

A Class Of Benzofuranoindoline-Bearing Heptacyclic Fungal Ripps With Anticancer Activities, Qiuyue Nie, Fanglong Zhao, Xuerong Yu, Mithun C Madhusudhanan, Caleb Chang, Siting Li, Sandipan Roy Chowdhury, Bryce Kille, Andy Xu, Rory Sharkey, Chunxiao Sun, Hongzhi Zeng, Shuai Liu, Dishu Zhou, Xin Yu, Kevin Yang, Sandra A C Figueiredo, Maria Zotova, Zichen Hu, Alan Y Du, Dongyin Guan, Rui Tang, Todd Treangen, Jin Wang, Pedro N Leão, Yang Gao, Junjie Chen, Peng Liu, Hans Renata, Xue Gao

Children’s Nutrition Research Center Staff Publications

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a promising source of new pharmaceuticals, yet the therapeutic potential of fungal RiPPs remains largely underexplored. Here, we report asperigimycins as a distinct class of fungal RiPPs, featuring a unique heptacyclic scaffold consisting of a benzofuranoindoline core and three additional macrocycles, primarily assembled by six distinct fungi-specific DUF3328 oxidases. Inspired by the enhancement of anticancer activity through the N-terminal pyroglutamate in naturally occurring asperigimycins C and D, we chemically modify the inactive asperigimycin B with a series of lipid substitutions at its N-terminus. A derivative with a C-11 linear fatty …

Pact Is Requisite For Prostate Cancer Cell Proliferation, Dianne J. Beveridge, Andrew J. Woo, Kirsty L. Richardson, Rikki A.M. Brown, Lisa M. Stuart, Manjot Singh, Andrew D. Redfern, Peter J. Leedman

Research outputs 2022 to 2026

PACT (encoded by the PRKRA gene) is a double-stranded RNA binding protein with defined antiviral defense and cytoplasmic RNA-induced silencing actions in mammals. We previously described a further role for PACT as a modulator of nuclear receptor (NR)-regulated gene expression. Here, we investigated the role of PACT in prostate cancer (PCa) using a loss-of-function approach. Depletion of PACT in multiple PCa cell lines resulted in a reduction in cell proliferation, but viability was maintained. RNA-sequencing analysis of LNCaP PCa cells ± PACT revealed a depletion of biological processes involved in cell cycle, mitochondrial function, and NR-response pathways in the PACT …