Chemicals and Drugs Commons^™

Csf1r Inhibition Depletes Brain Macrophages And Reduces Brain Virus Burden In Siv-Infected Macaques, Diana G. Bohannon, Laurent D. Zablocki-Thomas, Evan S. Leung, Jinbum K. Dupont, Julian B. Hattler, Jolanta Kowalewska, Miaoyun Zhao, Jiangtao Luo, Marco Salemi, Angela M. Amedee, Qingsheng Li, Marcelo J. Kuroda, Woong-Ki Kim

School of Graduate Studies Faculty Publications

Perivascular macrophages (PVMs) and, to a lesser degree, microglia are targets and reservoirs of HIV and simian immunodeficiency virus (SIV) in the brain. Previously, we demonstrated that colony-stimulating factor 1 receptor (CSF1R) in PVMs was upregulated and activated in chronically SIV-infected rhesus macaques with encephalitis, correlating with SIV infection of PVMs. Herein, we investigated the role of CSF1R in the brain during acute SIV infection using BLZ945, a brain-penetrant CSF1R kinase inhibitor. Apart from three uninfected historic controls, nine Indian rhesus macaques were infected acutely with SIVmac251 and divided into three groups (n = 3 each): an untreated control and …

Genome-Wide Methylation Patterns In Primary Uveal Melanoma: Development Of Methylsig-Um, An Epigenomic Prognostic Signature To Improve Patient Stratification, Emilie Lalonde, Dong Li, Kathryn Ewens, Carol L. Shields, Arupa Ganguly

Wills Eye Hospital Papers

Despite studies highlighting the prognostic utility of DNA methylation in primary uveal melanoma (pUM), it has not been translated into a clinically useful tool. We sought to define a methylation signature to identify newly diagnosed individuals at high risk for developing metastasis. Methylation profiling was performed on 41 patients with pUM with stage T2-T4 and at least three years of follow-up using the Illumina Infinium HumanMethylation450K BeadChip (N = 24) and the EPIC BeadChip (N = 17). Findings were validated in the TCGA cohort with known metastatic outcome (N = 69). Differentially methylated probes were identified in patients who developed …

Diesel Exhaust Particles Alter Mitochondrial Bioenergetics And Camp Producing Capacity In Human Bronchial Epithelial Cells, Isabella Cattani-Cavalieri, Marina Trombetta-Lima, Hong Yan, Ana L. Manzano-Covarrubias, Hoeke A. Baarsma, Asmaa Oun, Melissa Mol Van Der Veen, Emily Oosterhout, Amalia M. Dolga, Rennolds S. Ostrom, Samuel Santos Valenca, Martina Schmidt

Pharmacy Faculty Articles and Research

Introduction: Air pollution from diesel combustion is linked in part to the generation of diesel exhaust particles (DEP). DEP exposure induces various processes, including inflammation and oxidative stress, which ultimately contribute to a decline in lung function. Cyclic AMP (cAMP) signaling is critical for lung homeostasis. The impact of DEP on cAMP signaling is largely unknown.

Methods: We exposed human bronchial epithelial (BEAS-2B) cells to DEP for 24–72 h and evaluated mitochondrial bioenergetics, markers of oxidative stress and inflammation and the components of cAMP signaling. Mitochondrial bioenergetics was measured at 72 h to capture the potential and accumulative effects of …

Innovation Path At Institute For Protein Design Of Washington University And Its Enlightenment For Construction Of New Life Sciences R&D Institutions, Runzhou Zhao, Ming Ni, Yunzhi Fa, Xiaochen Bo, Jian Jiao

Bulletin of Chinese Academy of Sciences (Chinese Version)

The Institute for Protein Design (IPD) at the University of Washington is a pioneering local and state-supported non-profit scientific research institution. Since its establishment in 2012, IPD has seized the opportunity of AI for Science and open science, and continuously enhanced its capabilities of fundamental innovations, breakthrough technologies, and industrial impact. We summarized five factors contributing to IPD’s development, including focusing on the cutting-edge issues of basic scientific research to gain a first-mover advantage and then further expand, integrating AI-enhanced digital tools and solid experimental validations, facilitating the integrated development of innovation and industrial chains, giving full play to the …

Roles Of Hydrogen Sulfide (H2s) As A Potential Therapeutic Agent In Cardiovascular Diseases: A Narrative Review, Kazi N. Islam, Ivan D. Nguyen, Rahib Islam, Humza Pirzadah, Hassan Malik

School of Medicine Faculty Publications

Cardiovascular disease (CVD) stands as one of the leading causes of morbidity and mortality worldwide, and the continued search for novel therapeutics is vital for addressing this global health challenge. Over the past decade, hydrogen sulfide (H₂S) has garnered significant attention in the field of medical research, as it has been proven to be a cardioprotective gaseous signaling molecule. It joins nitric oxide and carbon monoxide as endogenously produced gasotransmitters. As for its mechanism, H₂S functions through the posttranslational addition of a sulfur group to cysteine residues on target proteins in a process called sulfhydration. As a result, the observed …

Association Of High Fibrinogen To Albumin Ratio With Long-Term Mortality In Patients With Spontaneous Intracerebral Hemorrhage, Shiping Chen, Yu Zhang, Yangchun Xiao, Xin Cheng, Liyuan Peng, Yixin Tian, Tiangui Li, Jialing He, Pengfei Hao, Weelic Chong, Yang Hai, Chao You, Fang Fang

Department of Medical Oncology Faculty Papers

BACKGROUND: The association between fibrinogen-to-albumin ratio (FAR) and in-hospital mortality in patients with spontaneous intracerebral hemorrhage (ICH) has been established. However, the association with long-term mortality in spontaneous ICH remains unclear. This study aims to investigate the association between FAR and long-term mortality in these patients.

METHODS: Our retrospective study involved 3,538 patients who were diagnosed with ICH at West China Hospital, Sichuan University. All serum fibrinogen and serum albumin samples were collected within 24 h of admission and participants were divided into two groups according to the FAR. We conducted a Cox proportional hazard analysis to evaluate the association …

Allopurinol: Clinical Considerations In The Development And Treatment Of Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, And Other Associated Drug Reactions, Kathryn M. Dillman, Alison M. Hawkins, Amanda R. Ragland, Grace C. Wester, Driskell R. Greene, Giustino Varrassi, Peyton Moore, Raju Behara, Shahab Ahmadzadeh, Harish Siddaiah, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Allopurinol lowers urate production through the inhibition of xanthine oxidase. It is oxidatively hydroxylated to oxypurinol and is the most prescribed medication for gout treatment. Although it has a beneficial effect in the treatment of this common disease, like many medications, it is also known for having numerous adverse effects. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), diseases that exist on a spectrum, are two of the most dangerous adverse effects associated with allopurinol use. These immune-mediated disease processes involve almost every organ system. They are essential to recognize as early as possible, as they could potentially be deadly, …

Cholesterol Drugs May Improve Periodontal Disease

New Orleans Dental Association News

Recently, statin treatment applied locally into tissues during both surgical and nonsurgical procedures exhibiting a positive effect on various parameters of periodontal tissue health. When looking at this novel, not yet commonly utilized approach to the local application of statins as an adjunct to periodontal treatment, early studies have shown significant improvement in clinical parameters, such as probing depth and clinical attachment levels. This method of local statin delivery into the tissue shows promise, and should be explored by further research.

The Potential Anti-Arrhythmic Effect Of Sglt2 Inhibitors, Hong-Yi Duan, Hector Barajas-Martinez, Charles Antzelevitch, Dan Hu

Department of Medicine Faculty Papers

Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) were initially recommended as oral anti-diabetic drugs to treat type 2 diabetes (T2D), by inhibiting SGLT2 in proximal tubule and reduce renal reabsorption of sodium and glucose. While many clinical trials demonstrated the tremendous potential of SGLT2i for cardiovascular diseases. 2022 AHA/ACC/HFSA guideline first emphasized that SGLT2i were the only drug class that can cover the entire management of heart failure (HF) from prevention to treatment. Subsequently, the antiarrhythmic properties of SGLT2i have also attracted attention. Although there are currently no prospective studies specifically on the anti-arrhythmic effects of SGLT2i. We provide clues from …

Toward The Development Of A Pan-Lyssavirus Vaccine, Sabrine Ben Hamed, Jacob Myers, Anisha Chandwani, Christoph Wirblich, Drishya Kurup, Nir Paran, Matthias Schnell

Department of Microbiology and Immunology Faculty Papers

In addition to the rabies virus (RABV), 16 more lyssavirus species have been identified worldwide, causing a disease similar to RABV. Non-rabies-related human deaths have been described, but the number of cases is unknown, and the potential of such lyssaviruses causing human disease is unpredictable. The current rabies vaccine does not protect against divergent lyssaviruses such as Mokola virus (MOKV) or Lagos bat virus (LBV). Thus, a more broad pan-lyssavirus vaccine is needed. Here, we evaluate a novel lyssavirus vaccine with an attenuated RABV vector harboring a chimeric RABV glycoprotein (G) in which the antigenic site I of MOKV replaces …

A Fungal Metabolic Regulator Underlies Infectious Synergism During Candida Albicans-Staphylococcus Aureus Intra-Abdominal Co-Infection, Saikat Paul, Olivia A. Todd, Kara R. Eichelberger, Christine Tkaczyk, Bret R. Sellman, Mairi C. Noverr, James E. Cassat, Paul L. Fidel, Brian M. Peters

School of Dentistry Faculty Publications

Candida albicans and Staphylococcus aureus are two commonly associated pathogens that cause nosocomial infections with high morbidity and mortality. Our prior and current work using a murine model of polymicrobial intra-abdominal infection (IAI) demonstrates that synergistic lethality is driven by Candida-induced upregulation of functional S. aureus α-toxin leading to polymicrobial sepsis and organ damage. In order to determine the candidal effector(s) mediating enhanced virulence, an unbiased screen of C. albicans transcription factor mutants was undertaken revealing that zcf13Δ/Δ fails to drive augmented α-toxin or lethal synergism during co-infection. A combination of transcriptional and phenotypic profiling approaches shows that ZCF13 regulates …

Conformational Alterations Of The Cell Surface Of Monomeric And Dimeric Β2m-Free Hla-I (Proto-Hla) May Enable Novel Immune Functions In Health And Disease, Mepur Ravindranath, Narendranath Ravindranath, Carly Amato-Menker, Fatiha El Hilali, Edward Filippone

Division of Nephrology Faculty Papers

Human leukocyte antigens (HLAs) are polymorphic glycoproteins expressed on the cell surface of nucleated cells and consist of two classes, HLA class I and HLA class II. In contrast, in mice, these molecules, known as H-2, are expressed on both nucleated cells and erythrocytes. HLA-I molecules (Face-1) are heterodimers consisting of a polypeptide heavy chain (HC) and a light chain, B2-microglobulin (B2m). The heterodimers bind to antigenic peptides and present them to the T-cell receptors of CD8+ cytotoxic T lymphocytes. The HCs can also independently emerge on the cell surface as B2m-free HC monomers without peptides (Face-2). Early investigators suggested …

The Evolving Role Of Chlorthalidone And Hydrochlorothiazide As First-Line Treatments For Hypertensive Patients, Alan D. Kaye, Sarah C. Corley, Ellen Ingram, Peter P. Issa, Logan T. Roberts, Elisa E. Neuchat, Matthew J. Sharpe, Nicolette Doan, Olga Willett, Adam M. Kaye, Sahar Shekoohi, Giustino Varrassi

School of Medicine Faculty Publications

Hypertension is attributable long-term to various negative health outcomes, including atherosclerotic cardiovascular disease and, more broadly, to cardiovascular events such as congestive heart disease, myocardial infarction, heart failure, and stroke. Effective hypertension treatment is essential to lower the risk of these outcomes. Treatment of hypertension includes both nonpharmacologic and, if necessary, pharmacologic interventions. The drug classes proven in trials to decrease the risk of cardiovascular disease events in cases with hypertension include angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, thiazide diuretics, and calcium channel blockers. When considering thiazide diuretics as a first-line treatment, chlorthalidone (CTD) is currently recommended by the American …

Successful Rapid Benzodiazepine Detoxification In An Acute Care Hospital: A Case Report, Taku Harada, Kazuki Tatebayashi, Mori Nakai

Journal of Community Hospital Internal Medicine Perspectives

Introduction: Benzodiazepine (BZD) dependence and withdrawal are significant public health concerns, affecting 15–30% of regular users within 4-6 weeks of administration. Rapid BZD tapering protocols in acute care settings can mitigate withdrawal symptoms and facilitate rehabilitation, yet are challenging due to variability in patient responses. Case Presentation: We report a case of a 67-year-old male with a history of high-dose BZD use for panic disorder and depression and recent mild ischemic stroke, presenting with worsening left lower limb paralysis. The patient's complex medication regimen included multiple BZDs and other psychotropic drugs. Given the risks associated with high-dose BZD use, particularly …

Emerging Treatments And Therapies For Autism Spectrum Disorder: A Narrative Review, Alan D. Kaye, Kaitlyn E. Allen, Van S. Smith Iii, Victoria T. Tong, Vivian E. Mire, Huy Nguyen, Zachary Lee, Maria Kouri, Carlo Jean Baptiste, Chizoba N. Mosieri, Adam M. Kaye, Giustino Varrassi, Sahar Shekoohi

School of Medicine Faculty Publications

The prevalence of autism spectrum disorder (ASD) has increased over the last decade. In this regard, many emerging therapies have been described as ASD therapies. Although ASD does not have a cure, there are several management options available that can help reduce symptom severity. ASD is highly variable and, therefore, standard treatment protocols and studies are challenging to perform. Many of these therapies also address comorbidities for which patients with ASD have an increased risk. These concurrent diagnoses can include psychiatric and neurological disorders, including attention deficit and hyperactivity disorder, anxiety disorders, and epilepsy, as well as gastrointestinal symptoms such …

Interleukin 24 Induces Apoptosis Through Glycogen Synthase Kinase-3 Beta Inactivation In Prostate Cancer Cells, Sual J. Lopez, Moira Sauane

Theses and Dissertations

Interleukin 24 (IL-24) is a tumor-suppressing protein currently in clinical trials. IL-24 induces cancer-specific apoptosis by activating endoplasmic reticulum (ER) stress and mitochondria dysfunction. We have previously demonstrated that IL-24 leads to apoptosis in cancer cells by protein kinase A (PKA) activation in human breast cancer cells. To further understand the mechanism by which IL-24 induces apoptosis, I analyzed the role of glycogen synthase kinase-3 (GSK3), a highly conserved and normally active serine/threonine kinase in cancer cells and downstream target of PKA. The work reported here provides direct evidence that GSK3 was inhibited following IL-24 treatment in human prostate cancer …

Uses Of Herbal Extracts In Endodontology: A Literature Review, Reem Chamseddine, Roula S. Abiad

BAU Journal - Science and Technology

The use of natural herbal extracts in the field of dentistry, and specifically in endodontology had gained a high popularity in the past few years. The main objective of endodontic treatment is to prevent and eliminate the infection from the root canal, seize the invasion of microorganisms to periradicular tissues and preserve the natural dentition. Studies had shown that some herbs are better alternatives to traditional chemical irrigants or medicaments used in root canal treatment, based on their potential antimicrobial effect, smear layer removal capabilities, tissue dissolution effect, antioxidant, anti-inflammatory and regenerative properties. Aim: The purpose of this literature review …

Cryotherapy In The Field Of Endodontics: A Literature Review, Amena Al Bast, Roula S. Abiad

BAU Journal - Science and Technology

Cryotherapy is a recent approach in the field of endodontics. It is a remedy that subject tissue to low temperature. Low temperature induces vasoconstriction limiting inflammation, pain and edema and analgesia by reducing the nerve conduction velocity. The aim of this review is to point out the different and recent clinical applications of cryotherapy in the field of endodontics and to describe its physiology and its effect regarding postoperative pain and inflammation. A literature search from PubMed, Scopus, ScienceDirect and EBSCO databases and other resources using specific keywords results in articles to determine the effect of applying cryotherapy in the …

Loss Of Hormone Receptor Expression After Exposure To Fluid Shear Stress In Breast Cancer Cell Lines, Jonathan Cuccia, Braulio Andres Ortega Quesada, Ethan P. Littlefield, Alejandra M. Ham, Matthew E. Burow, Adam T. Melvin, Elizabeth C. Martin

School of Medicine Faculty Publications

Following metastatic spread, many hormone receptor positive (HR(+)) patients develop a more aggressive phenotype with an observed loss of the HRs estrogen receptor (ER) and progesterone receptor (PR). During metastasis, breast cancer cells are exposed to high magnitudes of fluid shear stress (FSS). Unfortunately, the role for FSS on the regulation of HR expression and function during metastasis is not fully understood. This study was designed to elucidate the impact of FSS on HR(+) breast cancer. Utilizing a microfluidic platform capable of exposing breast cancer cells to FSS that mimics in situ conditions, we demonstrate the impact of FSS exposure …

Cutaneous Wound Healing And The Effects Of Cannabidiol, Pearl Shah, Kathryne Holmes, Fairouz Chibane, Phillip Wang, Pablo Chagas, Evila Salles, Melanie Jones, Patrick Palines, Mohamad Masoumy, Babak Baban, Jack Yu

School of Medicine Faculty Publications

Cutaneous wounds, both acute and chronic, begin with loss of the integrity, and thus barrier function, of the skin. Surgery and trauma produce acute wounds. There are 22 million surgical procedures per year in the United States alone, based on data from the American College of Surgeons, resulting in a prevalence of 6.67%. Acute traumatic wounds requiring repair total 8 million per year, 2.42% or 24.2 per 1000. The cost of wound care is increasing; it approached USD 100 billion for just Medicare in 2018. This burden for wound care will continue to rise with population aging, the increase in …