Medicine and Health Sciences Commons^™

Histone Demethylase Phf8 Drives Neuroendocrine Prostate Cancer Progression By Epigenetically Upregulating Foxa2., Qiuli Liu, Jian Pang, Lin-Ang Wang, Zhuowei Huang, Jing Xu, Xingxia Yang, Qiubo Xie, Yiqiang Huang, Tang Tang, Dali Tong, Gaolei Liu, Luofu Wang, Dianzheng Zhang, Qiang Ma, Hualiang Xiao, Weihua Lan, Jun Qin, Jun Jiang

PCOM Scholarly Papers

Neuroendocrine prostate cancer (NEPC) is a more aggressive subtype of castration-resistant prostate cancer (CRPC). Although it is well established that PHF8 can enhance prostate cancer cell proliferation, whether PHF8 is involved in prostate cancer initiation and progression is relatively unclear. By comparing the transgenic adenocarcinoma of the mouse prostate (TRAMP) mice with or without Phf8 knockout, we systemically examined the role of PHF8 in prostate cancer development. We found that PHF8 plays a minimum role in initiation and progression of adenocarcinoma. However, PHF8 is essential for NEPC because not only is PHF8 highly expressed in NEPC but also animals without …

Piwi-Interacting Rnas: Mitochondria-Based Biogenesis And Functions In Cancer, Jin-Fen Su, Anthony Concilla, Dianzheng Zhang, Fang Zhao, Fang-Fang Shen, Hao Zhang, Fu-You Zhou

PCOM Scholarly Papers

PIWI-interacting RNA (piRNAs), once thought to be mainly functioning in germlines, are now known to play an essential role in somatic and cancerous tissues. Ping-pong cycle initiation and mitochondria-based phased production constitute the core of the piRNA biogenesis and these two processes are well conserved in mammals, including humans. By being involved in DNA methylation, histone marker deposition, mRNA degradation, and protein modification, piRNAs also contribute to carcinogenesis partly due to oncogenic stress-induced piRNA dysregulation. Also, piRNAs play important roles in cancer stemness, drug resistance, and tumor immunology. Results from liquid biopsy analysis of piRNA can be used in both …

A Baker's Dozen Of Top Antimicrobial Stewardship Intervention Publications In 2019, Kayla R Stover, Elias B Chahine, David Cluck, Sarah Green, Daniel B Chastain, Darrell Childress, Carmen Faulkner-Fennell, Katherine Lusardi, Edo-Abasi U. Mcgee, Michelle Turner, P Brandon Bookstaver, Christopher M Bland

PCOM Scholarly Papers

Staying current on literature related to antimicrobial stewardship can be challenging given the ever-increasing number of published articles. The Southeastern Research Group Endeavor (SERGE-45) identified antimicrobial stewardship-related peer-reviewed literature that detailed an actionable intervention for 2019. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight the actionable intervention used by antimicrobial stewardship programs to provide key stewardship literature for teaching and training and to identify potential intervention opportunities within one's institution.

Lipocalin-2 Deficiency May Predispose To The Progression Of Spontaneous Age-Related Adiposity In Mice, Keya Meyers, María López, Joanna Ho, Savannah Wills, Srujana Rayalam, Shashidharamurthy Taval

PCOM Scholarly Papers

Lipocalin-2 (Lcn2) is an innate immune protein elevated by several orders of magnitude in various inflammatory conditions including aging and obesity. Recent studies have shown that Lcn2 is secreted by adipocytes in response to inflammation and is categorized as a new adipokine cross-linking innate immunity and metabolic disorders including obesity. However, the involvement of Lcn2 and its function during the progression of obesity is largely unknown. Recently, browning of white adipose tissue (WAT) has gained attention as a therapeutic strategy to combat obesity. Herein, we have shown that treatment of mature 3T3-L1 adipocytes with recombinant Lcn2 (rec-Lcn2) resulted in the …

Perinatal Docosahexaenoic Acid Supplementation Improves Cognition And Alters Brain Functional Organization In Piglets., Xi Fang, Wenwu Sun, Julie Jeon, Michael Azain, Holly Kinder, Jeongyoun Ahn, Hee Cheol Chung, Ryan S Mote, Nikolay M Filipov, Qun Zhao, Srujana Rayalam, Hea Jin Park

PCOM Scholarly Papers

Epidemiologic studies associate maternal docosahexaenoic acid (DHA)/DHA-containing seafood intake with enhanced cognitive development; although, it should be noted that interventional trials show inconsistent findings. We examined perinatal DHA supplementation on cognitive performance, brain anatomical and functional organization, and the brain monoamine neurotransmitter status of offspring using a piglet model. Sows were fed a control (CON) or a diet containing DHA (DHA) from late gestation throughout lactation. Piglets underwent an open field test (OFT), an object recognition test (ORT), and magnetic resonance imaging (MRI) to acquire anatomical, diffusion tensor imaging (DTI), and resting-state functional MRI (rs-fMRI) at weaning. Piglets from DHA-fed …

Perspectives On The Intracellular Bacterium Chlamydia Pneumoniae In Late-Onset Dementia, Brian J. Balin Phd

PCOM Scholarly Papers

Purpose of Review

Chronic diseases remain a daunting challenge for clinicians and researchers alike. While difficult to completely understand, most chronic diseases, including late-onset dementias, are thought to arise as an interplay between host genetic factors and environmental insults. One of the most diverse and ubiquitous environmental insults centers on infectious agents. Associations of infectious agents with late-onset dementia have taken on heightened importance, including our investigations of infection by the intracellular respiratory bacterium, Chlamydia pneumoniae (Cpn), in late-onset dementia of the Alzheimer’s type.

Recent Findings

Over the last two decades, the relationship of this infection to pathogenesis …

Correlation Of Ape1 With Vegfa And Cd163+ Macrophage Infiltration In Bladder Cancer And Their Prognostic Significance, Lin-Ang Wang, Bo Yang, Tang Tang, Yuxin Yang, Dianzheng Zhang, Hualing Xiao, Jing Xu, Luofu Wang, Li Lin, Jun Jiang

PCOM Scholarly Papers

The present study sought to estimate the applicability of apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1), vascular endothelial growth factor A (VEGFA) expression and CD163+ tumor‑associated macrophage (TAM) ratio as prognostic factors in bladder cancer (BCa). A total of 127 patients with bladder urothelial cancer who underwent radical cystectomy at Daping Hospital were recruited between January 2013 and January 2017, including 45 cases of non‑muscle invasive BCa (NMIBC) and 82 of MIBC. Immunohistochemical detection of APE1, VEGFA and CD163, as well as multiple immunofluorescence staining for APE1, VEGFA, CD163 and CD34, were performed on tissue samples. For APE1 and VEGFA, the staining was …

Convergent Evolution Of Conserved Mitochondrial Pathways Underlies Repeated Adaptation To Extreme Environments, Ryan Greenway, Nick Barts, Chathurika Henpita, Anthony P Brown, Lenin Arias Rodriguez, Carlos M Rodríguez Peña, Sabine Arndt, Gigi Y Lau, Michael P Murphy, Lei Wu, Dingbo Lin, Michael Tobler, Joanna L Kelley, Jennifer H. Shaw

PCOM Scholarly Papers

Extreme environments test the limits of life; yet, some organisms thrive in harsh conditions. Extremophile lineages inspire questions about how organisms can tolerate physiochemical stressors and whether the repeated colonization of extreme environments is facilitated by predictable and repeatable evolutionary innovations. We identified the mechanistic basis underlying convergent evolution of tolerance to hydrogen sulfide (H₂S)-a toxicant that impairs mitochondrial function-across evolutionarily independent lineages of a fish (Poecilia mexicana, Poeciliidae) from H₂S-rich springs. Using comparative biochemical and physiological analyses, we found that mitochondrial function is maintained in the presence of H₂S in sulfide …

Myo/Nog Cells Expressing Muscle Proteins Are Present In Preretinal Membranes From Patients With Proliferative Vitreoretinopathy., Jacquelyn Gerhart, Nathan Morrison, Lindsay Gugerty, David Telander, Arturo Bravo Nuevo, Mindy George-Weinstein

PCOM Scholarly Papers

Proliferative vitreoretinopathy (PVR) is a complication of rhegmatogenous retinal detachment and ocular trauma. The disease is characterized by development of membranes that may apply traction to the retina and cause redetachment. Membrane contractions are attributed to myofibroblasts arising from retinal pigment epithelial cells, glia and fibroblasts. The progenitors of myofibrobasts in the lens are Myo/Nog cells that express the skeletal muscle transcription factor MyoD and bone morphogenetic protein inhibitor Noggin. The retina and choroid also contain Myo/Nog cells that respond to stress. We examined preretinal PVR membranes from three ocular trauma patients with retinal detachment for Myo/Nog cells and their …

Are We Meeting The Demand For Pharmacist-Led Antimicrobial Stewardship Programs During Postgraduate Training-Year 1 (Pgy1)?, Edo-Abasi U. Mcgee, Arrington D Mason-Callaway, Brent L. Rollins

PCOM Scholarly Papers

In the United States of America, pharmacists play a pivotal role in antimicrobial stewardship; training from postgraduate residency may hone knowledge and skills gained from didactic pharmacy education. Specifically, the first year of postgraduate training, the learner may become an "everyday steward in training" and may go on to complete a second year in infectious diseases. However, there are a limited number of second year infectious diseases programs. The current demand for pharmacist to participate in and or lead stewardship is disproportionate to available specialized training. The first year of post-graduate training has to be setup to ensure appropriate preparation, …

Hypogeusia As The Initial Presenting Symptom Of Covid-19, Lauren E Melley, Eli Bress, Erik Polan

PCOM Scholarly Papers

COVID-19 is the disease caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first arose in Wuhan, China, in December 2019 and has since been declared a pandemic. The clinical sequelae vary from mild, self-limiting upper respiratory infection symptoms to severe respiratory distress, acute cardiopulmonary arrest and death. Otolaryngologists around the globe have reported a significant number of mild or otherwise asymptomatic patients with COVID-19 presenting with olfactory dysfunction. We present a case of COVID-19 resulting in intensive care unit (ICU) admission, presenting with the initial symptom of disrupted taste and flavour perception prior to respiratory …

The Toxic Effect Of Mobile Phone Radiation On Rabbit Organs, Shudong Zhu, Yan Zhu, Hao Li, Doudou Zhang, Dianzheng Zhang

PCOM Scholarly Papers

Whether electromagnetic radiation (EMR) emitted from mobile phones is hazardous to human health is largely unknown. We investigated the effects of mobile phone radiation on critical organs in a rabbit model by exposing the animals to mobile phone radiation with sub-thermal specific absorption rate (SAR) of 1.0 and 0.7 W/kg for the head and the body, respectively, for 16 weeks (6 h/day, 6 days/week). There is no apparent change at the organ level. However, H&E staining showed that radiation-exposure significantly increased inflammatory cell infiltration in the liver and the lungs with a lesser degree of myocardial cell cytoplasmic vacuolation. In …

Flexibility And Adaptation: Key Elements For Preserving Research Continuity During The Covid-19 Pandemic, Mindy George-Weinstein

PCOM Scholarly Papers

Limiting the spread of the coronavirus by social-distancing has eclipsed nearly all normal daily activities and routines. Healthcare services for those with COVID-19 and protection of vulnerable populations have escalated exponentially. State and local governments are mandating closure of non-essential businesses while classifying operations of pharmaceutical and biotechnology companies as essential. Education of students at all levels is, for the most part, virtual across the U.S.

Emerging Therapeutic Strategies For Covid-19 Patients, Shudong Zhu, Xialing Guo, Kyla Geary, Dianzheng Zhang

PCOM Scholarly Papers

Over 100,000 cases of COVID-19 patients infected with the novel coronavirus SARS-COV-2 have been reported worldwide in approximately 2 months, resulting in over 3000 deaths. Potential therapeutic strategies, including remdesivir, chloroquine phosphate, abidol, lopinavir/ritonavir, plasma, antibody, vaccine and stem cells are discussed in this review. With the number of patients increasing daily, there is an urgent need for effective therapeutic intervention.

Cost-Effectiveness Model Shows Superiority Of Wireless Spinal Cord Stimulation Implantation Without A Separate Trial., Richard B North, Harish S. Parihar, Shawn D. Spencer, Arthur F Spalding, Jane Shipley

PCOM Scholarly Papers

OBJECTIVE: We evaluated the cost-effectiveness of wireless spinal cord stimulation (Wireless SCS) with single stage "direct to permanent" implantation vs. screening with temporary electrodes and an external pulse generator followed by implantation of a system for long-term use (IPG SCS).

MATERIALS AND METHODS: We created a cost model that takes a 2019 United States (U.S.) payer perspective and is based on IPG SCS cost models for subjects with chronic back and/or leg pain. Our six-month decision tree includes the screening trial period (success ≥50% relief) and leads to various levels of pain relief with or without complications for IPG SCS …

Case Report: Co-Existence Of Brca2 And Palb2 Germline Mutations In Familial Prostate Cancer With Solitary Lung Metastasis., Tang Tang, Lin-Ang Wang, Peng Wang, Dali Tong, Gaolei Liu, Jun Zhang, Nan Dai, Yao Zhang, Gang Yuan, Kyla Geary, Dianzheng Zhang, Qiuli Liu, Jun Jiang

PCOM Scholarly Papers

Background: Mutation-caused loss-of-function of factors involved in DNA damage response (DDR) is responsible for the development and progression of ~20% of prostate cancer (PCa). Some mutations can be used in cancer risk assessment and informed treatment decisions.

Methods: Target capture-based deep sequencing of 11 genes was conducted with total DNA purified from the proband's peripheral blood. Sanger sequencing was conducted to screen potential germline mutations in the proband's family members. Targeted sequencing of a panel of 1,021 genes was done with DNA purified from the tumor tissue.

Results: Two previously unreported germline mutations in the DDR pathway,

Conclusions: The newly …

Interleukin 1Β And Prostaglandin E2 Affect Expression Of Dna Methylating And Demethylating Enzymes In Human Gingival Fibroblasts, Sara Seutter, Jacquay Winfield, Alexis Esbitt, Samantha Snyder, Anastasia Magner, Kristine Kim, Craig Carcuffe, Jeremy Schmoyer, Payvand Kamrani, Jason Mercando, Seyed M Shamseddin, Kevan Green, Ruth C. Borghaei

PCOM Scholarly Papers

Periodontitis is a common chronic inflammatory condition that results in increased levels of inflammatory cytokines and inflammatory mediators. In addition to oral disease and tooth loss, it also causes low-grade systemic inflammation that contributes to development of systemic conditions including cardiovascular disease, pre-term birth, diabetes and cancer. Chronic inflammation is associated with epigenetic change, and it has been suggested that such changes can alter cell phenotypes in ways that contribute to both ongoing inflammation and development of associated pathologies. Here we show that exposure of human gingival fibroblasts to IL-1β increases expression of maintenance methyltransferase DNMT1 but decreases expression of …

High Fat Diet Significantly Changed The Global Gene Expression Profile Involved In Hepatic Drug Metabolism And Pharmacokinetic System In Mice., Yuqi He, Tao Yang, Yimei Du, Lin Qin, Feifei Ma, Zunping Wu, Hua Ling, Li Yang, Zhengtao Wang, Qingdi Zhou, Guangbo Ge, Yanliu Lu

PCOM Scholarly Papers

Background: High fat diet impact transcription of hepatic genes responsible for drug metabolism and pharmacokinetics. Until now, researches just focused on a couple specific genes without a global profile showing. Age-dependent manner was also not noted well. This study aims to investigate the high fat diet effect on transcriptome of drug metabolism and pharmacokinetic system in mouse livers and show the age-dependent evidence.

Methods: C57BL/6 male mice were used in this experiment. High fat diet was used to treat mice for 16 and 38 weeks. Serum total cholesterol, low density lipoprotein cholesterol, aspartate transaminase, and alanine transaminaselevels were measured. Meanwhile, …

Lsd1 Promotes Bladder Cancer Progression By Upregulating Lef1 And Enhancing Emt., Qiubo Xie, Tang Tang, Jian Pang, Jing Xu, Xingxia Yang, Linang Wang, Yiqiang Huang, Zhuowei Huang, Gaolei Liu, Dali Tong, Yao Zhang, Luofu Wang, Dianzheng Zhang, Weihua Lan, Qiuli Liu, Jun Jiang

PCOM Scholarly Papers

Epithelial-to-mesenchymal transition (EMT) is one of the important underlying molecular mechanisms for most types of cancers including bladder cancer. The precise underlying molecular mechanism in EMT-mediated bladder cancer progression is far from completed. LSD1, a histone lysine-specific demethylase, is known to promote cancer cell proliferation, metastasis, and chemoresistance. We found in this study that LSD1 is highly upregulated in bladder cancer specimens, especially those underwent chemotherapy, and the elevated levels of LSD1 are highly associated with bladder cancer grades, metastasis status, and prognosis. Inhibiting or knockdown LSD1 repressed not only EMT process but also cancer progression. Mechanistically, LSD1 complexes with …

The Vhl/Hif Axis In The Development And Treatment Of Pheochromocytoma/Paraganglioma, Song Peng, Jun Zhang, Xintao Tan, Yiqiang Huang, Jing Xu, Natalie Silk, Dianzheng Zhang, Qiuli Liu, Jun Jiang

PCOM Scholarly Papers

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors originating from chromaffin cells in the adrenal medulla (PCCs) or extra-adrenal sympathetic or parasympathetic paraganglia (PGLs). About 40% of PPGLs result from germline mutations and therefore they are highly inheritable. Although dysfunction of any one of a panel of more than 20 genes can lead to PPGLs, mutations in genes involved in the VHL/HIF axis including

Assessing The Elevation Of Cardiac Biomarkers And The Severity Of Covid-19 Infection: A Meta-Analysis, Cucnhat Walker, Subrata Deb, Hua Ling, Zhe Wang

PCOM Scholarly Papers

- Purpose: Since December 2019, coronavirus disease 2019 infection has become a global pandemic. The cases of Coronavirus Disease 2019 (COVID-19)-related acute cardiac injury with unknown pathophysiologic mechanism has become increasingly prevalent. However, it is not yet understood how the extent of cardiac injury differs with the intensity of viral infection. In the current study, we aimed to assess the association between elevated cardiac biomarkers and the severity of COVID-19 infection.

METHODS: A systematic literature search was performed across PubMed and Embase databases from December 1, 2019 to July 10, 2020, to identify studies that reported cardiac biomarkers of troponin …

Revision Of The Eocene 'Platyrhina' Species From The Bolca Lagerstätte (Italy) Reveals The First Panray (Batomorphii: Zanobatidae) In The Fossil Record, Giuseppe Marramà, Giorgio Carnevale, Kerin M. Claeson, Gavin J P Naylor, Jürgen Kriwet

PCOM Scholarly Papers

The fossil-Lagerstätte of Bolca (Italy) is well known for the diversity and exquisite preservation of its bony and cartilaginous fishes documenting tropical shallow-water marine environments associated with coral reefs in the western Tethys during the early Eocene. In this study, the taxonomic, systematic and phylogenetic position of two batoid species traditionally assigned to the living thornback ray genus Platyrhina is re-evaluated. †Platyrhina bolcensis Heckel, 1851 is recognized as a separate species of the Platyrhinidae because of its plate-like antorbital cartilage with an irregular outline and a small horn on the nasal capsules. Also, the rostral cartilage does not reach …

Brain-Specific Angiogenesis Inhibitor 1 Is Expressed In The Myo/Nog Cell Lineage., Jacquelyn Gerhart, Jessica Bowers, Lindsay Gugerty, Colby Gerhart, Mark Martin, Fathma Abdalla, Arturo Bravo Nuevo, Jonathan Tabb Sullivan, Rebecca Rimkunas, Amie Albertus, Lou Casta, Lori Getts, Robert Getts, Mindy George-Weinstein

PCOM Scholarly Papers

The Myo/Nog cell lineage was discovered in the chick embryo and is also present in adult mammalian tissues. The cells are named for their expression of mRNA for the skeletal muscle specific transcription factor MyoD and bone morphogenetic protein inhibitor Noggin. A third marker for Myo/Nog cells is the cell surface molecule recognized by the G8 monoclonal antibody (mAb). G8 has been used to detect, track, isolate and kill Myo/Nog cells. In this study, we screened a membrane proteome array for the target of the G8 mAb. The array consisted of >5,000 molecules, each synthesized in their native confirmation with …

Myo/Nog Cells Are Nonprofessional Phagocytes, Jacquelyn Gerhart, Lindsay Gugerty, Paul Lecker, Fathma Abdalla, Mark Martin, Olivia Gerhart, Colby Gerhart, Karanveer Johal, Jake Bernstein, John Spikes, Keith Mathers, Arturo Bravo Nuevo, Mindy George-Weinstein

PCOM Scholarly Papers

Myo/Nog cells were discovered in the chick embryo epiblast. Their expression of MyoD reflects a commitment to the skeletal muscle lineage and capacity to differentiate into myofibroblasts. Release of Noggin by Myo/Nog cells is essential for normal morphogenesis. Myo/Nog cells rapidly respond to wounding in the skin and eyes. In this report, we present evidence suggesting that Myo/Nog cells phagocytose tattoo ink in tissue sections of human skin and engulf cell corpses in cultures of anterior human lens tissue and magnetic beads injected into the anterior chamber of mice in vivo. Myo/Nog cells are distinct from macrophages in the skin …