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Microbial Interactions Among Gardnerella, Prevotella And Fannyhessea Prior To Incident Bacterial Vaginosis: Protocol For A Prospective, Observational Study, Christina A. Muzny, Jacob H. Elnaggar, Lúcia G.V. Sousa, Ângela Lima, Kristal J. Aaron, Isaac C. Eastlund, Keonte J. Graves, Chaoling Dong, Olivia T. Van Gerwen, Meng Luo, Ashutosh Tamhane, Dustin Long, Nuno Cerca, Christopher M. Taylor Feb 2024

Microbial Interactions Among Gardnerella, Prevotella And Fannyhessea Prior To Incident Bacterial Vaginosis: Protocol For A Prospective, Observational Study, Christina A. Muzny, Jacob H. Elnaggar, Lúcia G.V. Sousa, Ângela Lima, Kristal J. Aaron, Isaac C. Eastlund, Keonte J. Graves, Chaoling Dong, Olivia T. Van Gerwen, Meng Luo, Ashutosh Tamhane, Dustin Long, Nuno Cerca, Christopher M. Taylor

School of Graduate Studies Faculty Publications

Introduction The aetiology of bacterial vaginosis (BV), a biofilm-associated vaginal infection, remains unknown. Epidemiologic data suggest that it is sexually transmitted. BV is characterised by loss of lactic acid-producing lactobacilli and an increase in facultative and strict anaerobic bacteria. Gardnerella spp are present in 95%–100% of cases; Gardnerella vaginalis has been found to be more virulent than other BV-associated bacteria (BVAB) in vitro. However, G. vaginalis is found in women with normal vaginal microbiota and colonisation is not sufficient for BV development. We hypothesise that Gardnerella spp initiate BV biofilm formation, but incident BV (iBV) requires incorporation of other key …


Effects Of Extraction Methods On The Structural Characteristics And Functional Properties Of Dietary Fiber Extracted From Papaya Peel And Seed, Xiaoyu Feng, Kashif Ameer, Guihun Jiang, Karna Ramachandraiah Feb 2024

Effects Of Extraction Methods On The Structural Characteristics And Functional Properties Of Dietary Fiber Extracted From Papaya Peel And Seed, Xiaoyu Feng, Kashif Ameer, Guihun Jiang, Karna Ramachandraiah

School of Medicine Faculty Publications

This study aimed to characterize dietary fibers (DF) produced from papaya peel (PP) and seed (PS) using three different extraction methods (acidic: AC, enzymatic: EN and alkaline: AL). The scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), thermal and rheological properties, X-ray diffraction (XRD), monosaccharide composition were adopted for characterizing DF samples. All the DF samples showed representative infrared spectral features and crystalline structure, whereas DF derived from PP and PS extracted by AC had looser and more complicated structures. DF derived from PP and PS extracted by EN displayed greater thermal stability among DFs. DF extracted by PP-AC …


Radiofrequency Ablation Of Thyroid Nodules: A Clinical Review Of Treatment Complications, Peter P. Issa, Katherine Cironi, Leely Rezvani, Emad Kandil Jan 2024

Radiofrequency Ablation Of Thyroid Nodules: A Clinical Review Of Treatment Complications, Peter P. Issa, Katherine Cironi, Leely Rezvani, Emad Kandil

School of Medicine Faculty Publications

Radiofrequency ablation (RFA) is a minimally invasive ablative modality for the treatment of thyroid nodules. Reports of RFA use have demonstrated an impressive safety profile and excellent volume reduction rates between 60-90%. Given its increased popularity in the United States as well as globally, numerous recent works have been published and a discussant of relevant complications incorporating recent insight may assist practitioners in minimizing complications and optimizing patient outcomes. Herein, we provide a comprehensive and updated review of the reported complications and side effects following RFA, summarizing their frequency and clinical presentation. We also describe a means of minimizing such …


Targeted Repression Of Topa By Crispri Reveals A Critical Function For Balanced Dna Topoisomerase I Activity In The Chlamydia Trachomatis Developmental Cycle, Li Shen, Leiqiong Gao, Abigail R. Swoboda, Scot P. Ouellette Jan 2024

Targeted Repression Of Topa By Crispri Reveals A Critical Function For Balanced Dna Topoisomerase I Activity In The Chlamydia Trachomatis Developmental Cycle, Li Shen, Leiqiong Gao, Abigail R. Swoboda, Scot P. Ouellette

School of Medicine Faculty Publications

Chlamydia trachomatis is an obligate intracellular bacterium that is responsible for the most prevalent bacterial sexually transmitted infection. Changes in DNA topology in this pathogen have been linked to its pathogenicity-associated developmental cycle. Here, evidence is provided that the balanced activity of DNA topoisomerases contributes to controlling Chlamydia developmental processes. Utilizing catalytically inactivated Cas12 (dCas12)-based clustered regularly interspaced short palindromic repeats interference (CRISPRi) technology, we demonstrate targeted knockdown of chromosomal topA transcription in C. trachomatis without detected toxicity of dCas12. Repression of topA impaired the developmental cycle of C. trachomatis mostly through disruption of its differentiation from a replicative form …


Interplay Between Acetylation And Ubiquitination Of Imitation Switch Chromatin Remodeler Isw1 Confers Multidrug Resistance In Cryptococcus Neoformans, Yang Meng, Yue Ni, Zhuoran Li, Tianhang Jiang, Tianshu Sun, Yanjian Li, Xindi Gao, Hailong Li, Chenhao Suo, Chao Li, Sheng Yang, Tian Lan, Guojian Liao, Tongbao Liu, Ping Wang, Chen Ding Jan 2024

Interplay Between Acetylation And Ubiquitination Of Imitation Switch Chromatin Remodeler Isw1 Confers Multidrug Resistance In Cryptococcus Neoformans, Yang Meng, Yue Ni, Zhuoran Li, Tianhang Jiang, Tianshu Sun, Yanjian Li, Xindi Gao, Hailong Li, Chenhao Suo, Chao Li, Sheng Yang, Tian Lan, Guojian Liao, Tongbao Liu, Ping Wang, Chen Ding

School of Medicine Faculty Publications

Cryptococcus neoformans poses a threat to human health, but anticryptococcal therapy is hampered by the emergence of drug resistance, whose underlying mechanisms remain poorly understood. Herein, we discovered that Isw1, an imitation switch chromatin remodeling ATPase, functions as a master modulator of genes responsible for in vivo and in vitro multidrug resistance in C. neoformans. Cells with the disrupted ISW1 gene exhibited profound resistance to multiple antifungal drugs. Mass spectrometry analysis revealed that Isw1 is both acetylated and ubiquitinated, suggesting that an interplay between these two modification events exists to govern Isw1 function. Mutagenesis studies of acetylation and ubiquitination sites …


Blood And Mri Biomarkers Of Mild Traumatic Brain Injury In Non-Concussed Collegiate Football Players, Eunhan Cho, Joshua Granger, Bailey Theall, Nathan Lemoine, Derek Calvert, Jack Marucci, Shelly Mullenix, Hollis O’Neal, Tomas Jacome, Brian A. Irving, Neil M. Johannsen, Owen Carmichael, Guillaume Spielmann Jan 2024

Blood And Mri Biomarkers Of Mild Traumatic Brain Injury In Non-Concussed Collegiate Football Players, Eunhan Cho, Joshua Granger, Bailey Theall, Nathan Lemoine, Derek Calvert, Jack Marucci, Shelly Mullenix, Hollis O’Neal, Tomas Jacome, Brian A. Irving, Neil M. Johannsen, Owen Carmichael, Guillaume Spielmann

School of Medicine Faculty Publications

Football has one of the highest incidence rates of mild traumatic brain injury (mTBI) among contact sports; however, the effects of repeated sub-concussive head impacts on brain structure and function remain under-studied. We assessed the association between biomarkers of mTBI and structural and functional MRI scans over an entire season among non-concussed NCAA Division I linemen and non-linemen. Concentrations of S100B, GFAP, BDNF, NFL, and NSE were assessed in 48 collegiate football players (32 linemen; 16 non-linemen) before the start of pre-season training (pre-camp), at the end of pre-season training (pre-season), and at the end of the competitive season (post-season). …


Genital Tract Infections, The Vaginal Microbiome And Gestational Age At Birth Among Pregnant Women In South Africa: A Cohort Study Protocol, Ranjana M.S. Gigi, Mandisa M. Mdingi, Hyunsul Jung, Shantelle Claassen-Weitz, Lukas Bütikofer, Jeffrey D. Klausner, Christina A. Muzny, Christopher M. Taylor, Janneke H.H.M. Van De Wijgert, Remco P.H. Peters, Nicola Low Dec 2023

Genital Tract Infections, The Vaginal Microbiome And Gestational Age At Birth Among Pregnant Women In South Africa: A Cohort Study Protocol, Ranjana M.S. Gigi, Mandisa M. Mdingi, Hyunsul Jung, Shantelle Claassen-Weitz, Lukas Bütikofer, Jeffrey D. Klausner, Christina A. Muzny, Christopher M. Taylor, Janneke H.H.M. Van De Wijgert, Remco P.H. Peters, Nicola Low

School of Medicine Faculty Publications

Introduction Preterm birth complications are the most common cause of death in children under 5 years. The presence of multiple microorganisms and genital tract inflammation could be the common mechanism driving early onset of labour. South Africa has high levels of preterm birth, genital tract infections and HIV infection among pregnant women. We plan to investigate associations between the presence of multiple lower genital tract microorganisms in pregnancy and gestational age at birth. Methods and analysis This cohort study enrols around 600 pregnant women at one public healthcare facility in East London, South Africa. Eligible women are ≥18 years and …


Metalloproteomic Investigation Of Hg-Binding Proteins In Renal Tissue Of Rats Exposed To Mercury Chloride, Emerson Carlos De Almeida, Victor Diego Faria, Felipe Dalmazzo Cirinêu, Maria G.A. Santiago, Beatriz Miotto, José C.S. Vieira, Camila Pereira Braga, Jiri Adamec, Ana A.H. Fernandes, Marília A.R. Buzalaf, Pedro De Magalhães Padilha Dec 2023

Metalloproteomic Investigation Of Hg-Binding Proteins In Renal Tissue Of Rats Exposed To Mercury Chloride, Emerson Carlos De Almeida, Victor Diego Faria, Felipe Dalmazzo Cirinêu, Maria G.A. Santiago, Beatriz Miotto, José C.S. Vieira, Camila Pereira Braga, Jiri Adamec, Ana A.H. Fernandes, Marília A.R. Buzalaf, Pedro De Magalhães Padilha

School of Medicine Faculty Publications

Results obtained from rat studies indicate that, even at low concentrations, mercurial species cause harmful effects on the kidneys, by inducing the nephrotic oxidative stress response. In the present work, Hg-associated proteins were identified as possible mercury-exposure biomarkers in rat kidneys exposed to low mercury chloride concentrations for 30 days (Hg-30) and 60 days (Hg-60), using metalloproteomic strategies. The renal proteomic profile was fractioned by two-dimensional electrophoresis and the mercury determinations in kidney samples, protein pellets and protein spots were performed using graphite furnace atomic absorption spectrometry. The characterization of Hg-associated protein spots and the analysis of differentially expressed proteins …


Association Of Chlamydia Trachomatis Burden With The Vaginal Microbiota, Bacterial Vaginosis, And Metronidazole Treatment, Caleb M. Ardizzone, Christopher M. Taylor, Evelyn Toh, Rebecca A. Lillis, Jacob H. Elnaggar, John W. Lammons, Patricia Dehon Mott, Emily L. Duffy, Li Shen, Alison J. Quayle Dec 2023

Association Of Chlamydia Trachomatis Burden With The Vaginal Microbiota, Bacterial Vaginosis, And Metronidazole Treatment, Caleb M. Ardizzone, Christopher M. Taylor, Evelyn Toh, Rebecca A. Lillis, Jacob H. Elnaggar, John W. Lammons, Patricia Dehon Mott, Emily L. Duffy, Li Shen, Alison J. Quayle

School of Graduate Studies Faculty Publications

Bacterial vaginosis (BV), a dysbiosis of the vaginal microbiota, is a common coinfection with Chlamydia trachomatis (Ct), and BV-associated bacteria (BVAB) and their products have been implicated in aiding Ct evade natural immunity. Here, we determined if a non-optimal vaginal microbiota was associated with a higher genital Ct burden and if metronidazole, a standard treatment for BV, would reduce Ct burden or aid in natural clearance of Ct infection. Cervicovaginal samples were collected from women at enrollment and, if testing positive for Ct infection, at a follow-up visit approximately one week later. Cervical Ct burden was assessed by inclusion forming …


The Dose-Response Effect Of Aerobic Exercise On Inflammation In Colon Cancer Survivors, Justin C. Brown, Stephanie L.E. Compton, Jeffrey A. Meyerhardt, Guillaume Spielmann, Shengping Yang Dec 2023

The Dose-Response Effect Of Aerobic Exercise On Inflammation In Colon Cancer Survivors, Justin C. Brown, Stephanie L.E. Compton, Jeffrey A. Meyerhardt, Guillaume Spielmann, Shengping Yang

School of Medicine Faculty Publications

Background; Physical activity after surgical resection for colon cancer is associated with significantly longer disease-free survival. Inflammation is hypothesized to mediate the association between physical activity and disease-free survival in colon cancer. Methods; In this exploratory analysis of a randomized dose-response trial, 39 colon cancer survivors who completed standard therapy were stratified by cancer stage and randomized in a 1;1;1 ratio to one of three treatment groups for 24 weeks of usual-care control, 150 min/wk of moderate-intensity aerobic exercise (low-dose), or 300 min/wk of moderate-intensity aerobic exercise (high-dose). Inflammation outcomes included high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL6), and soluble tumor …


Clinical Outcomes And Tumor Microenvironment Response To Radiofrequency Ablation Therapy: A Systematic Review And Meta-Analysis, Lauren E. Mueller, Peter P. Issa, Mohammad Hosny Hussein, Rami M. Elshazli, Muhib Haidari, Youssef Errami, Mohamed Shama, Manal S. Fawzy, Emad Kandil, Eman Toraih Jul 2023

Clinical Outcomes And Tumor Microenvironment Response To Radiofrequency Ablation Therapy: A Systematic Review And Meta-Analysis, Lauren E. Mueller, Peter P. Issa, Mohammad Hosny Hussein, Rami M. Elshazli, Muhib Haidari, Youssef Errami, Mohamed Shama, Manal S. Fawzy, Emad Kandil, Eman Toraih

School of Medicine Faculty Publications

Background: Radiofrequency ablation (RFA) utilizes minimally invasive high-energy current to precisely ablate tumor cells. It has been utilized in many cancer types including thyroid, lung, and liver cancer. It has been shown to provide adequate ablative margins with minimal complications; however, incomplete RFA may lead to recurrence of tumor. The underlying cellular mechanism and behavior of ablated cancer tissue is poorly understood. Methods: A systematic review was performed, searching EMBASE, Web of Science, PubMed, and Scopus for studies published up to July 2022 and reported following PRISMA guidelines. Collection was performed by two groups of investigators to avoid risk of …


Radiofrequency Ablation As A Treatment Modality For Primary Hyperparathyroidism: A Systematic Literature Review, Peter P. Issa, Emad Kandil, Grace S. Lee Jun 2023

Radiofrequency Ablation As A Treatment Modality For Primary Hyperparathyroidism: A Systematic Literature Review, Peter P. Issa, Emad Kandil, Grace S. Lee

School of Medicine Faculty Publications

Background: Primary hyperparathyroidism (pHPT) is an endocrine disorder typically characterized by elevated serum calcium and elevated parathyroid hormone (PTH). While parathyroidectomy is the standard treatment, non-operative intervention such as radiofrequency ablation (RFA) has been adopted as an alternative for the management of pHPT, as it has been utilized in other endocrine glands such as thyroid and adrenal. In this literature review, we aim to evaluate the current practice of RFA for pHPT. Methods: A systematic literature search using PubMed, Web of Science, and Embase through June 2022 was conducted. Studies included in the review consisted of patient cohorts who had …


A Clinical Practice Review Of Percutaneous Ethanol Injection For Thyroid Nodules: State Of The Art For Benign, Cystic Lesions, Robert D.E. Clark, Xinyi Luo, Peter P. Issa, Ralph P. Tufano, Emad Kandil May 2023

A Clinical Practice Review Of Percutaneous Ethanol Injection For Thyroid Nodules: State Of The Art For Benign, Cystic Lesions, Robert D.E. Clark, Xinyi Luo, Peter P. Issa, Ralph P. Tufano, Emad Kandil

School of Medicine Faculty Publications

Percutaneous ethanol injection (PEI) is a widely used treatment option for cystic and predominantly cystic thyroid nodules. It has several advantages over other treatment modalities. Compared to surgery, PEI is less painful, can be performed in the outpatient setting, and carries less risk of transient or permanent side effects. Compared to other minimally invasive techniques such as radiofrequency ablation (RFA), PEI is less expensive and does not require specialized equipment. PEI performs well in the context of cystic nodules. PEI does not perform as well as other techniques in solid nodules, so its use as a primary treatment is limited …


Impact Of Testosterone Use On The Vaginal Microbiota Of Transgender Men, Including Susceptibility To Bacterial Vaginosis: Study Protocol For A Prospective, Observational Study, Christina A. Muzny, Olivia T. Van Gerwen, Julia A. Schroeder, Emma Sophia Kay-Duncan, Krishmita Siwakoti, Kristal J. Aaron, Isaac C. Eastlund, Keonte J. Graves, Jacob H. Elnaggar, Ashutosh Tamhane, Dustin Long, Nicholas Van Wagoner, Evelyn Toh, Christopher M. Taylor Mar 2023

Impact Of Testosterone Use On The Vaginal Microbiota Of Transgender Men, Including Susceptibility To Bacterial Vaginosis: Study Protocol For A Prospective, Observational Study, Christina A. Muzny, Olivia T. Van Gerwen, Julia A. Schroeder, Emma Sophia Kay-Duncan, Krishmita Siwakoti, Kristal J. Aaron, Isaac C. Eastlund, Keonte J. Graves, Jacob H. Elnaggar, Ashutosh Tamhane, Dustin Long, Nicholas Van Wagoner, Evelyn Toh, Christopher M. Taylor

School of Graduate Studies Faculty Publications

Introduction The effect of testosterone (T) therapy on the vaginal microbiota of transgender men (TGM) is not well characterised, although one cross-sectional study comparing the vaginal microbiota of cisgender women to TGM on T≥1 year found that, in 71% of the TGM, the vaginal microbiota was less likely to be Lactobacillus-dominated and more likely to be enriched with >30 other bacterial species, many associated with bacterial vaginosis (BV). This prospective study aims to investigate changes in the composition of the vaginal microbiota over time in TGM who retain their natal genitalia (ie, vagina) and initiate T. In addition, we will …


Chronic Alcohol Exposure Induces Hepatocyte Damage By Inducing Oxidative Stress, Satb2 And Stem Cell-Like Characteristics, And Activating Lipogenesis, Wei Yu, Yiming Ma, Sushant K. Shrivastava, Rakesh K. Srivastava, Sharmila Shankar Apr 2022

Chronic Alcohol Exposure Induces Hepatocyte Damage By Inducing Oxidative Stress, Satb2 And Stem Cell-Like Characteristics, And Activating Lipogenesis, Wei Yu, Yiming Ma, Sushant K. Shrivastava, Rakesh K. Srivastava, Sharmila Shankar

School of Medicine Faculty Publications

Alcohol is a risk factor for hepatocellular carcinoma (HCC). However, the molecular mechanism by which chronic alcohol consumption contributes to HCC is not well understood. The purpose of the study was to demonstrate the effects of chronic ethanol exposure on the damage of human normal hepatocytes. Our data showed that chronic exposure of hepatocytes with ethanol induced changes similar to transformed hepatocytes that is, exhibited colonies and anchorage-independent growth. These damaged hepatocytes contained high levels of reactive oxygen species (ROS) and showed induction of the SATB2 gene. Furthermore, damaged hepatocytes gained the phenotypes of CSCs which expressed stem cell markers …


Targeted Osmotic Lysis: A Novel Approach To Targeted Cancer Therapies, Harry J. Gould, Dennis Paul Apr 2022

Targeted Osmotic Lysis: A Novel Approach To Targeted Cancer Therapies, Harry J. Gould, Dennis Paul

School of Medicine Faculty Publications

The conventional treatment of cancer has been based on the delivery of non-selective toxins and/or ionizing energy that affect both the cancer and normal tissues in the hope of destroying the offending disease before killing the patient. Unfortunately, resistance often develops to these treatments and patients experience severe, dose-limiting adverse effects that reduce treatment efficacy and compromise quality of life. Recent advances in our knowledge of the biology of tumor cells and their microenvironment, the recognition of surface proteins that are unique to specific cancers and essential to cell growth and survival and signaling pathways associate with invasion and metastasis …


The Efficacy And Safety Of Roxadustat For The Treatment Of Anemia In Non-Dialysis Dependent Chronic Kidney Disease Patients: An Updated Systematic Review And Meta-Analysis Of Randomized Clinical Trials, Basel Abdelazeem, Joseph Shehata, Kirellos Said Abbas, Nahla Ahmed El-Shahat, Bilal Malik, Pramod Savarapu, Mostafa Eltobgy, Arvind Kunadi Apr 2022

The Efficacy And Safety Of Roxadustat For The Treatment Of Anemia In Non-Dialysis Dependent Chronic Kidney Disease Patients: An Updated Systematic Review And Meta-Analysis Of Randomized Clinical Trials, Basel Abdelazeem, Joseph Shehata, Kirellos Said Abbas, Nahla Ahmed El-Shahat, Bilal Malik, Pramod Savarapu, Mostafa Eltobgy, Arvind Kunadi

School of Medicine Faculty Publications

Background Roxadustat (ROX) is a new medication for anemia as a complication of chronic kidney disease (CKD). Our meta-analysis aims to evaluate the efficacy and safety of ROX, especially on the cardiovascular risks, for anemia in NDD-CKD patients. Methods Electronic databases were searched systematically from inception to July 2021 to look for randomized control trials (RCTs) that evaluated ROX NDD-CKD patients. Hemoglobin level and iron utilization parameters, including ferritin, serum iron, transferrin saturation (TSAT), total iron-binding capacity (TIBC), transferrin, and hepcidin were analyzed for efficacy. Pooled risk ratios (RRs) and standardized mean differences (SMDs) were calculated and presented with their …


Soy Formula Is Not Estrogenic And Does Not Result In Reproductive Toxicity In Male Piglets: Results From A Controlled Feeding Study, Martin J.J. Ronis, Horacio Gomez‐Acevedo, Kartik Shankar, Leah Hennings, Neha Sharma, Michael L. Blackburn, Isabelle Miousse, Harry Dawson, Celine Chen, Kelly E. Mercer, Thomas M. Badger Mar 2022

Soy Formula Is Not Estrogenic And Does Not Result In Reproductive Toxicity In Male Piglets: Results From A Controlled Feeding Study, Martin J.J. Ronis, Horacio Gomez‐Acevedo, Kartik Shankar, Leah Hennings, Neha Sharma, Michael L. Blackburn, Isabelle Miousse, Harry Dawson, Celine Chen, Kelly E. Mercer, Thomas M. Badger

School of Graduate Studies Faculty Publications

Soy infant formula which is fed to over half a million infants per year contains isoflavones such as genistein, which have been shown to be estrogenic at high concentrations. The developing testis is sensitive to estrogens, raising concern that the use of soy formulas may result in male reproductive toxicity. In the current study, male White‐Dutch Landrace piglets received either sow milk (Sow), or were provided milk formula (Milk), soy formula (Soy), milk formula supplemented with 17‐beta‐estradiol (2 mg/kg/d) (M + E2) or supplemented with genistein (84 mg/L of diet; (M + G) from postnatal day 2 until day 21. …


Combination Of Tipifarnib And Sunitinib Overcomes Renal Cell Carcinoma Resistance To Tyrosine Kinase Inhibitors Via Tumor-Derived Exosome And T Cell Modulation, Jacob W. Greenberg, Hogyoung Kim, Miae Ahn, Ahmed A. Moustafa, He Zhou, Pedro C. Barata, A. Hamid Boulares, Asim B. Abdel-Mageed, Louis S. Krane Feb 2022

Combination Of Tipifarnib And Sunitinib Overcomes Renal Cell Carcinoma Resistance To Tyrosine Kinase Inhibitors Via Tumor-Derived Exosome And T Cell Modulation, Jacob W. Greenberg, Hogyoung Kim, Miae Ahn, Ahmed A. Moustafa, He Zhou, Pedro C. Barata, A. Hamid Boulares, Asim B. Abdel-Mageed, Louis S. Krane

School of Graduate Studies Faculty Publications

Background: Tyrosine kinase inhibitors (TKI) were initially demonstrated as an efficacious treatment for renal cell carcinoma (RCC). However, after a median treatment length of 14 months, a vast majority of patients develop resistance. This study analyzed a combination therapy of tipifarnib (Tipi) + sunitinib that targeted exosome-conferred drug resistance. Methods: 786-O, 786-O-SR (sunitinib resistant), A498, A498-SR, Caki-2, Caki-2-SR, and 293T cells were cultured. Ex-osomes were collected using differential ultracentrifugation. Cell proliferation, Jurkat T cell immune assay, and immunoblot analysis were used for downstream analysis. Results: SR exosomes treatment displayed a cytotoxic effect on immune cells. This cytotoxic effect was associated …


Trait Energy And Fatigue May Be Connected To Gut Bacteria Among Young Physically Active Adults: An Exploratory Study, Ali Boolani, Karyn M. Gallivan, Kristin S. Ondrak, Courtney J. Christopher, Hector F. Castro, Shawn R. Campagna, Christopher M. Taylor, Meng Luo, Scot E. Dowd, Matthew Lee Smith, Lauri O. Byerley Jan 2022

Trait Energy And Fatigue May Be Connected To Gut Bacteria Among Young Physically Active Adults: An Exploratory Study, Ali Boolani, Karyn M. Gallivan, Kristin S. Ondrak, Courtney J. Christopher, Hector F. Castro, Shawn R. Campagna, Christopher M. Taylor, Meng Luo, Scot E. Dowd, Matthew Lee Smith, Lauri O. Byerley

School of Medicine Faculty Publications

Recent scientific evidence suggests that traits energy and fatigue are two unique unipolar moods with distinct mental and physical components. This exploratory study investigated the correlation between mental energy (ME), mental fatigue (MF), physical energy (PE), physical fatigue (PF), and the gut microbiome. The four moods were assessed by survey, and the gut microbiome and metabolome were determined from 16 S rRNA analysis and untargeted metabolomics analysis, respectively. Twenty subjects who were 31 ± 5 y, physically active, and not obese (26.4 ± 4.4 kg/m2) participated. Bacteroidetes (45%), the most prominent phyla, was only negatively correlated with PF. The second …


Recent Advances In Our Molecular And Mechanistic Understanding Of Misfolded Cellular Proteins In Alzheimer’S Disease (Ad) And Prion Disease (Prd), Walter J. Lukiw Jan 2022

Recent Advances In Our Molecular And Mechanistic Understanding Of Misfolded Cellular Proteins In Alzheimer’S Disease (Ad) And Prion Disease (Prd), Walter J. Lukiw

School of Medicine Faculty Publications

Naturally occurring neuron-abundant proteins including amyloid Aβ42 peptide and the microtubule-associated protein tau (MAPT) can, over time and under pathological situations, assume atypical conformations, altering their normal biological structure and function, and causing them to aggregate into insoluble and neurotoxic intracellular inclusions. These misfolded proteins ultimately contribute to the pathogenesis of several progressive, age-related and ultimately lethal human neurodegenerative disorders. The molecular mechanism of this pathological phenomenon of neuronal protein misfolding lends support to the ‘prion hypothesis’, which predicts that the aberrant folding of endogenous natural protein structures into unusual pathogenic isoforms can induce the atypical folding of other similar …


New Inroads Into Our Understanding Of The Tauopathies, Alzheimer's Disease, And The Contribution Of Altered Protein Conformation To Human Neurological Disease, Walter J. Lukiw Jan 2022

New Inroads Into Our Understanding Of The Tauopathies, Alzheimer's Disease, And The Contribution Of Altered Protein Conformation To Human Neurological Disease, Walter J. Lukiw

School of Medicine Faculty Publications

No abstract provided.


Scaling Of Computed Tomography Body Composition To Height: Relevance Of Height-Normalized Indices In Patients With Colorectal Cancer, Justin C. Brown, Steven B. Heymsfield, Bette J. Caan Nov 2021

Scaling Of Computed Tomography Body Composition To Height: Relevance Of Height-Normalized Indices In Patients With Colorectal Cancer, Justin C. Brown, Steven B. Heymsfield, Bette J. Caan

School of Medicine Faculty Publications

Background: Body weight scales to height with a power of ≈2 (weight/height2), forming the basis of body mass index (BMI). The corresponding scaling of body composition measured by abdominal computed tomography (CT) to height has not been established. The objective of this analysis was to quantify the scaling of body composition measured by a single-slice axial abdominal CT image (skeletal muscle, and visceral, subcutaneous, and total adipose tissue) to height in patients with colorectal cancer (CRC). Methods: This cross-sectional study included non-Hispanic white males and females, aged 18–80 years, who were diagnosed with stage I–III CRC at an integrated health …


Corticotropin-Releasing Factor Infusion In The Bed Nucleus Of The Stria Terminalis Of Lactating Mice Alters Maternal Care And Induces Behavioural Phenotypes In Offspring, Kerstin Camile Creutzberg, Érika Kestering-Ferreira, Thiago Wendt Viola, Luis Eduardo Wearick-Silva, Rodrigo Orso, Bernardo Aguzzoli Heberle, Lucas Albrechet-Souza, Rosa Maria Martins De Almeida, Rodrigo Grassi-Oliveira Nov 2020

Corticotropin-Releasing Factor Infusion In The Bed Nucleus Of The Stria Terminalis Of Lactating Mice Alters Maternal Care And Induces Behavioural Phenotypes In Offspring, Kerstin Camile Creutzberg, Érika Kestering-Ferreira, Thiago Wendt Viola, Luis Eduardo Wearick-Silva, Rodrigo Orso, Bernardo Aguzzoli Heberle, Lucas Albrechet-Souza, Rosa Maria Martins De Almeida, Rodrigo Grassi-Oliveira

School of Medicine Faculty Publications

The peripartum period is accompanied by numerous physiological and behavioural adaptations organised by the maternal brain. These changes are essential for adequate expression of maternal behaviour, thereby ensuring proper development of the offspring. The corticotropin-releasing factor (CRF) plays a key role in a variety of behaviours accompanying stress, anxiety, and depression. There is also evidence that CRF contributes to maladaptations during the peripartum period. We investigated the effects of CRF in the bed nucleus of the stria terminalis (BNST) of lactating mice during maternal care and analysed locomotor activity and anxiety-like behaviour in the offspring. The BNST has been implicated …


Microrna-Based Biomarkers In Alzheimer’S Disease (Ad), Yuhai Zhao, Vivian Jaber, Peter N. Alexandrov, Andrea Vergallo, Simone Lista, Harald Hampel, Walter J. Lukiw Oct 2020

Microrna-Based Biomarkers In Alzheimer’S Disease (Ad), Yuhai Zhao, Vivian Jaber, Peter N. Alexandrov, Andrea Vergallo, Simone Lista, Harald Hampel, Walter J. Lukiw

School of Medicine Faculty Publications

Alzheimer’s disease (AD) is a multifactorial, age-related neurological disease characterized by complex pathophysiological dynamics taking place at multiple biological levels, including molecular, genetic, epigenetic, cellular and large-scale brain networks. These alterations account for multiple pathophysiological mechanisms such as brain protein accumulation, neuroinflammatory/neuro-immune processes, synaptic dysfunction, and neurodegeneration that eventually lead to cognitive and behavioral decline. Alterations in microRNA (miRNA) signaling have been implicated in the epigenetics and molecular genetics of all neurobiological processes associated with AD pathophysiology. These changes encompass altered miRNA abundance, speciation and complexity in anatomical regions of the CNS targeted by the disease, including modified miRNA expression …


Geographic And Intra-Racial Disparities In Early-Onset Colorectal Cancer In The Seer 18 Registries Of The United States, Wesal H. Abualkhair, Meijiao Zhou, Carolina O. Ochoa, Leonel Lacayo, Caitlin Murphy, Xiao Cheng Wu, Jordan J. Karlitz Oct 2020

Geographic And Intra-Racial Disparities In Early-Onset Colorectal Cancer In The Seer 18 Registries Of The United States, Wesal H. Abualkhair, Meijiao Zhou, Carolina O. Ochoa, Leonel Lacayo, Caitlin Murphy, Xiao Cheng Wu, Jordan J. Karlitz

School of Medicine Faculty Publications

Background: Although early-onset colorectal cancer (EOCRC) incidence rates (IRs) are increasing, geographic and intra-racial IR disparities are not well defined. Methods: 2000-2015 Surveillance, Epidemiology, and End Results (SEER) program CRC IR Analysis (170,434 cases) was performed from ages 30 to 60 in four US regions, 18 individual registries, metropolitan and nonmetropolitan locations and stratified by race. Analyses were conducted in 1-year and 5-year age increments. Results: Wide US regional EOCRC IR variations exist: For example, age 45 IRs in the south are 26.8/100,000, 36.0% higher than the West, 19.7/100,000 (p < 0.0001). Disparities magnify between individual registries: EOCRC IRs in highest risk registries were 177-348% (Alaska Natives), 75-200% (Hawaii), 76-128% (Louisiana), and 61-125% (Kentucky) higher than lowest risk registries depending on age. EOCRC IRs are 18.2%-25.6% higher in nonmetropolitan versus metropolitan settings. Wide geographic intra-racial disparities exist. Within the White population, the greatest IR difference (78.8%) was between Kentucky (5.9/100,000) and Los Angeles (3.3/100,000) in 30- to 34-year-olds (p <.0001). Within the Black population, the greatest difference (136.2%) was between rural Georgia (30.7/100,000) and California excluding San Francisco-Oakland/San Jose-Monterey/Los Angeles (13/100,000) in 40- to 44-year-olds (p = 0003). Conclusion: Marked geographic EOCRC disparities exist with disproportionately high IRs in Alaska Natives, Hawaii, and southern registries. Geographic intra-racial disparities are present within White and Black populations. In Blacks, there are disproportionately high EOCRC IRs in rural Georgia. Although vigilance is required in all populations, attention must be paid to these higher risk populations. Potential interventions include assuring early investigation of symptoms, targeting modifiable risk factors and utilizing earlier age 45 screening options supported by some guidelines.


Acute Systemic Inflammatory Response Alters Transcription Profile Of Genes Related To Immune Response And Ca 2+ Homeostasis In Hippocampus; Relevance To Neurodegenerative Disorders, Grzegorz A. Czapski, Yuhai Zhao, Walter J. Lukiw, Joanna B. Strosznajder Oct 2020

Acute Systemic Inflammatory Response Alters Transcription Profile Of Genes Related To Immune Response And Ca 2+ Homeostasis In Hippocampus; Relevance To Neurodegenerative Disorders, Grzegorz A. Czapski, Yuhai Zhao, Walter J. Lukiw, Joanna B. Strosznajder

School of Medicine Faculty Publications

Acute systemic inflammatory response (SIR) triggers an alteration in the transcription of brain genes related to neuroinflammation, oxidative stress and cells death. These changes are also characteristic for Alzheimer’s disease (AD) neuropathology. Our aim was to evaluate gene expression patterns in the mouse hippocampus (MH) by using microarray technology 12 and 96 h after SIR evoked by lipopolysaccharide (LPS). The results were compared with microarray analysis of human postmortem hippocampal AD tissues. It was found that 12 h after LPS administration the expression of 231 genes in MH was significantly altered (FC > 2.0); however, after 96 h only the S100a8 …


Dha Modulates Manf And Trem2 Abundance, Enhances Neurogenesis, Reduces Infarct Size, And Improves Neurological Function After Experimental Ischemic Stroke, Ludmila Belayev, Sung Ha Hong, Raul S. Freitas, Hemant Menghani, Shawn J. Marcell, Larissa Khoutorova, Pranab K. Mukherjee, Madigan M. Reid, Reinaldo B. Oria, Nicolas G. Bazan Aug 2020

Dha Modulates Manf And Trem2 Abundance, Enhances Neurogenesis, Reduces Infarct Size, And Improves Neurological Function After Experimental Ischemic Stroke, Ludmila Belayev, Sung Ha Hong, Raul S. Freitas, Hemant Menghani, Shawn J. Marcell, Larissa Khoutorova, Pranab K. Mukherjee, Madigan M. Reid, Reinaldo B. Oria, Nicolas G. Bazan

School of Medicine Faculty Publications

Aims: Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a secretory neurotrophic factor protein that promotes repair after neuronal injury. The microglia cell surface receptor (triggering receptor expressed on myeloid cells-2; TREM2) regulates the production of pro- and antiinflammatory mediators after stroke. Here, we study MANF and TREM2 expression after middle cerebral artery occlusion (MCAo) and explore if docosahexaenoic acid (DHA) treatment exerts a potentiating effect. Methods: We used 2 hours of the MCAo model in rats and intravenously administered DHA or vehicle at 3 hours after the onset of MCAo. Neurobehavioral assessment was performed on days 1, 3, 7, and 14; …


Direct Delivery Of Antisense Oligonucleotides To The Middle And Inner Ear Improves Hearing And Balance In Usher Mice, Jennifer J. Lentz, Bifeng Pan, Abhilash Ponnath, Christopher M. Tran, Carl Nist-Lund, Alice Galvin, Hannah Goldberg, Katelyn N. Robillard, Francine M. Jodelka, Hamilton E. Farris, Jun Huang, Tianwen Chen, Hong Zhu, Wu Zhou, Frank Rigo, Michelle L. Hastings, Gwenaëlle S.G. Géléoc Aug 2020

Direct Delivery Of Antisense Oligonucleotides To The Middle And Inner Ear Improves Hearing And Balance In Usher Mice, Jennifer J. Lentz, Bifeng Pan, Abhilash Ponnath, Christopher M. Tran, Carl Nist-Lund, Alice Galvin, Hannah Goldberg, Katelyn N. Robillard, Francine M. Jodelka, Hamilton E. Farris, Jun Huang, Tianwen Chen, Hong Zhu, Wu Zhou, Frank Rigo, Michelle L. Hastings, Gwenaëlle S.G. Géléoc

School of Medicine Faculty Publications

Usher syndrome is a syndromic form of hereditary hearing impairment that includes sensorineural hearing loss and delayed-onset retinitis pigmentosa (RP). Type 1 Usher syndrome (USH1) is characterized by congenital profound sensorineural hearing impairment and vestibular areflexia, with adolescent-onset RP. Systemic treatment with antisense oligonucleotides (ASOs) targeting the human USH1C c.216G>A splicing mutation in a knockin mouse model of USH1 restores hearing and balance. Herein, we explore the effect of delivering ASOs locally to the ear to treat hearing and vestibular dysfunction associated with Usher syndrome. Three localized delivery strategies were investigated in USH1C mice: inner ear injection, trans-tympanic membrane …


Hiv-1 Tat Protein Promotes Neuronal Dysfunction Through Disruption Of Micrornas, J Robert Chang, Ruma Mukerjee, Asen Bagashev, Luis Del Valle, Tinatin Chabrashvili, Brian J. Hawkins, Johnny J. He, Bassel E. Sawaya Nov 2011

Hiv-1 Tat Protein Promotes Neuronal Dysfunction Through Disruption Of Micrornas, J Robert Chang, Ruma Mukerjee, Asen Bagashev, Luis Del Valle, Tinatin Chabrashvili, Brian J. Hawkins, Johnny J. He, Bassel E. Sawaya

School of Medicine Faculty Publications

Over the last decade, small noncoding RNA molecules such as microRNAs (miRNAs) have emerged as critical regulators in the expression and function of eukaryotic genomes. It has been suggested that viral infections and neurological disease outcome may also be shaped by the influence of small RNAs. This has prompted us to suggest that HIV infection alters the endogenous miRNA expression patterns, thereby contributing to neuronal deregulation and AIDS dementia. Therefore, using primary cultures and neuronal cell lines, we examined the impact of a viral protein (HIV-1 Tat) on the expression of miRNAs due to its characteristic features such as release …