Digital Commons Network^™

Protein Profiling Analysis Of Platelets In Hypercoagulable State Of Β-Thalassemia/Hbe Patients, Puangpaka Chanpeng

Chulalongkorn University Theses and Dissertations (Chula ETD)

β-thalassemia/HbE is an inherited hemolytic anemia caused by defect in β-globin synthesis resulting in accumulation of excess α-globin chains in red blood cells. A hypercogulable state leading to high risk of thromboembolic event is one of the most common complications observed in this disease, particularly in patients with splenectomy. Previous studies suggested that increased platelet activation and coagulation factors in β-thalassemia/HbE intermediate patients promote the hypercoagulable state. However, the hypercoagulable state as well as the molecular mechanism regarding this pathogenesis in β-thalassemia/HbE is not yet well understood. This study aimed to identify proteins related to platelet activation and to hypercoagulable …

"C-Terminal Binding Protein 2" An Emerging Oncogene In Colon And Pancreatic Cancers, Ayesha Chawla

Theses and Dissertations

The C terminal binding proteins (CtBP) 1 and 2 are a family of transcriptional co-repressors overexpressed in a variety of cancers, and are frequently associated with poor prognosis and chemoresistance. CtBP has also been characterized in cell culture models as drivers of migration/invasion and epithelial-mesenchymal transition. CtBP mediates its transcriptional corepressor activity via its dehydrogenase domain, and inhibition of this domain interferes with CtBP oncogenic functions. The role of CtBP in APC mutant neoplasia remains obscure even though APC is responsible for degradation of both β-catenin and CtBP in suppressing colorectal tumorigenesis. Our prior work demonstrated that CtBP proteins can …

Advancing Vibrational Spectroscopy For Cellular And Sub Cellular Analysis: Raman Spectroscopy As An In Vitro Chemotherapeutic Screeening And Assessment Protocol, Zeineb Farhane

Doctoral

Vibrational spectroscopy, including Raman micro-spectroscopy, has attracted considerable attention over the last few years, as a powerful, non-invasive tool for clinical applications, especially in cancer diagnosis, in vivo and ex vivo. As a molecular fingerprinting technique with optical resolution, Raman micro-spectroscopy is able to monitor biochemical processes, drug uptake, efficacy and mode of action and mechanisms of interaction of chemotherapeutic drugs at a subcellular level. In vitro applications may be more strategically achievable, and can help guide drug design and discovery, and eventually evaluate To this end, different lung cell lines were used and Raman micro-spectroscopy was coupled to valuable …

Regulation Of Hnrnpa1 By Micrornas Controls The Mir-18a–K-Ras Axis In Chemotherapy-Resistant Ovarian Cancer, Cristian Rodriguez-Aguayo, Paloma Del C Monroig, Roxana S Redis, Emine Bayraktar, Maria I Almeida, Cristina Ivan, Enrique Fuentes-Mattei, Mohammed H Rashed, Arturo Chavez-Reyes, Bulent Ozpolat, Rahul Mitra, Anil K Sood, George A Calin, Gabriel Lopez-Berestein

Faculty, Staff and Student Publications

The regulation of microRNA (miRNA) biogenesis, function and degradation involves a range of mechanisms, including interactions with RNA-binding proteins. The potential contribution of regulatory miRNAs to the expression of these RNA interactor proteins that could control other miRNAs expression is still unclear. Here we demonstrate a regulatory circuit involving oncogenic and tumor-suppressor miRNAs and an RNA-binding protein in a chemotherapy-resistant ovarian cancer model. We identified and characterized miR-15a-5p and miR-25-3p as negative regulators of hnRNPA1 expression, which is required for the processing of miR-18a-3p, an inhibitor of the

Regulation Of Core Body Temperature And The Immune System Determines Species Longevity, Ian J. Martins

Research outputs 2014 to 2021

The anti-aging gene Sirtuin 1 has now major relevance to genetics and the fields of pharmacology, toxicology, neuroscience, immunology, biochemistry and cell/molecular biology. Advances in anti-aging therapy are now essential to prevent mitochondrial apoptosis to promote longevity with the prevention of accelerated ageing. Calorie restriction that maintains the anti-aging gens changes the core body temperature and promotes species longevity. Stress and calorie consumption are sensitive to Sirt 1 function with relevance heat shock protein 70 metabolism and mitochondrial biogenesis. Sirt 1 regulation of the circadian rhythm mediates melatonin effects on core body temperature regulation and immune responses. Diet and fat …

Effect Of Pulse Shaping On Subharmonic Aided Pressure Estimation In Vitro And In Vivo., Ipshita Gupta, John R. Eisenbrey, Maria Stanczak, Anush Sridharan, Jaydev K. Dave, Ji-Bin Liu, Christopher Hazard, Xinghua Wang, Ping Wang, Huiwen Li, Kirk Wallace, Flemming Forsberg

Department of Radiology Faculty Papers

OBJECTIVES: Subharmonic imaging (SHI) is a technique that uses the nonlinear oscillations of microbubbles when exposed to ultrasound at high pressures transmitting at the fundamental frequency ie, f

METHODS: Eight waveforms with different envelopes were optimized with respect to acoustic power at which the SHAPE study is most sensitive. The study was run with four input transmit cycles, first in vitro and then in vivo in three canines to select the waveform that achieved the best sensitivity for detecting changes in portal pressures using SHAPE. A Logiq 9 scanner with a 4C curvi-linear array was used to acquire 2.5 MHz …

Sports Cardiology: Core Curriculum For Providing Cardiovascular Care To Competitive Athletes And Highly Active People., Aaron L. Baggish Md, Robert W. Battle Md, James G. Beckerman Md, Alfred A. Bove Md, Phd, Rachel J. Lampert Md, Benjamin D. Levine Md, Mark S. Link Md, Matthew W. Martinez Md, Silvana M. Molossi Md, Phd, Jack Salerno Md, Meagan M. Wasfy Md, Rory B. Weiner Md, Michael S. Emery Md

Department of Medicine

The last few decades have seen substantial growth in the populations of competitive athletes and highly active people (CAHAP). Although vigorous physical exercise is an effective way to reduce the risk of cardiovascular (CV) disease, CAHAP remain susceptible to inherited and acquired CV disease, and may be most at risk for adverse CV outcomes during intense physical activity. Traditionally, multidisciplinary teams comprising athletic trainers, physical therapists, primary care sports medicine physicians, and orthopedic surgeons have provided clinical care for CAHAP. However, there is increasing recognition that a care team including qualified CV specialists optimizes care delivery for CAHAP. In recognition …

Pd-L1 Expressing Circulating Tumour Cells In Head And Neck Cancers, Arutha Kulasinghe, Chris Perry, Liz Kenny, Majid E. Warkiani, Colleen Nelson, Chamindie Punyadeera

Research outputs 2014 to 2021

Background

Blockade of the PD-1/PD-L1 immune checkpoint pathway is emerging as a promising immunotherapeutic approach for the management and treatment of head and neck cancer patients who do not respond to 1st/2nd line therapy. However, as checkpoint inhibitors are cost intensive, identifying patients who would most likely benefit from anti PD-L1 therapy is required. Developing a non-invasive technique would be of major benefit to the patient and to the health care system.

Case presentation

We report the case of a 56 year old man affected by a supraglottic squamous cell carcinoma (SCC). A CT scan showed a 20 mm right …

Babesiosis-Associated Immune Thrombocytopenia, Roshni Narurkar, Aleksandra Mamorska-Dyga, A Agarwal, John Nelson, Delong Liu

NYMC Faculty Publications

Thrombocytopenia is a common feature of babesiosis. The mechanism for thrombocytopenia in babesiosis remains elusive. We report a case of babesiosis with severe new onset immune thrombocytopenia (ITP). In addition to antibiotics treatment for babesiosis, ITP therapy was administered. ITP in the present case was most likely triggered by the babesia infection. The severity of ITP in this case was not proportional to the severity of parasitemia. The neoantigen triggering the autoimmune response in babesiosis requires further characterization.

Intravenous Formulation Of Het0016 Decreased Human Glioblastoma Growth And Iimplicated Survival Benefit In Rat Xenograft Models, M Jain, N Gamage, M Alsulami, A Shankar, B Achyut, Austin Guo, A Arbab, A Arbab

NYMC Faculty Publications

Glioblastoma (GBM) is a hypervascular primary brain tumor with poor prognosis. HET0016 is a selective CYP450 inhibitor, which has been shown to inhibit angiogenesis and tumor growth. Therefore, to explore novel treatments, we have generated an improved intravenous (IV) formulation of HET0016 with HPssCD and tested in animal models of human and syngeneic GBM. Administration of a single IV dose resulted in 7-fold higher levels of HET0016 in plasma and 3.6-fold higher levels in tumor at 60 min than that in IP route. IV treatment with HPssCD-HET0016 decreased tumor growth, and altered vascular kinetics in early and late treatment groups …

Exercise Medicine For Advanced Prostate Cancer, Nicolas H. Hart, Daniel A. Galvao, Robert Newton

Research outputs 2014 to 2021

Purpose of review:

Exercise is a provocative medicine, known for its preventive, complimentary and rehabilitative role in the management of cancer. Impressively, exercise is also emerging as a synergistic and targeted medicine to enhance symptom control, modulate tumour biology and delay disease progression, with the potential to increase overall survival. Given the complex clinical presentation of advanced prostate cancer patients and their omnipresent comorbidities, this review describes the current and potential role of exercise medicine in advanced prostate cancer.

Recent findings:

Exercise has been shown to be safe, feasible and effective for advanced prostate cancer patients, inclusive of patients with …

Targeting The Nrf2-Heme Oxygenase-1 Axis After Intracerebral Hemorrhage., Jing Chen-Roetling, Raymond F. Regan

Department of Emergency Medicine Faculty Papers

BACKGROUND: Injury to cells adjacent to an intracerebral hemorrhage (ICH) is likely mediated at least in part by toxins released from the hematoma that initiate complex and interacting injury cascades. Pharmacotherapies targeting a single toxin or pathway, even if consistently effective in controlled experimental models, have a high likelihood of failure in a variable clinical setting. Nuclear factor erythroid-2 related factor 2 (Nrf2) regulates the expression of heme oxygenase-1 (HO-1) and multiple other proteins with antioxidant and antiinflammatory effects, and may be a target of interest after ICH.

METHODS: Studies that tested the effect of HO and Nrf2 in models …

Adiponectin Partially Rescues High Glucose/High Fat-Induced Impairment Of Mitochondrial Biogenesis And Function In A Pgc-1Α Dependent Manner., H. Wang, W.-J. Yan, J.-L. Zhang, F.-Y. Zhang, C. Gao, Y.-J. Wang, W.B. Lau, L. Tao

Department of Emergency Medicine Faculty Papers

OBJECTIVE: Plasma adiponectin (APN) levels are decreased in diabetic patients. Dysfunctional mitochondrial biogenesis is involved in type 2 diabetes (T2DM) pathogenesis, by unclear mechanisms. The present study determined (1) whether myocardial mitochondrial biogenesis was impaired in cardiomyocytes exposed to a high glucose/high fat (HGHF) medium (a T2DM in vitro model), (2) the effects of APN administration upon mitochondrial biogenesis in cardiomyocytes affected by HGHF incubation, and 3) the involved underlying mechanisms.

MATERIALS AND METHODS: Neonatal rat ventricular myocytes (NRVMs) were isolated and incubated in HGHF medium. Mitochondrial function was assessed by ATP content, and fluorescent microscopic analysis of myocardial apoptosis …

Proteoglycan Neofunctions: Regulation Of Inflammation And Autophagy In Cancer Biology., Liliana Schaefer, Claudia Tredup, Maria A. Gubbiotti, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Inflammation and autophagy have emerged as prominent issues in the context of proteoglycan signaling. In particular, two small, leucine-rich proteoglycans, biglycan and decorin, play pivotal roles in the regulation of these vital cellular pathways and, as such, are intrinsically involved in cancer initiation and progression. In this minireview, we will address novel functions of biglycan and decorin in inflammation and autophagy, and analyze new emerging signaling events triggered by these proteoglycans, which directly or indirectly modulate these processes. We will critically discuss the dual role of proteoglycan-driven inflammation and autophagy in tumor biology, and delineate the potential mechanisms through which …

Retrospective Analysis Of Contact Sport Participation On Cognitive Function In Healthy Athletes, Lisa C. Martinez

Cal Poly Humboldt theses and projects

This study explored the effects of contact and limited contact sport participation on neurocognitive function in non-concussed collegiate and adolescent athletes over time. Athletes participating in contact and limited contact sports have an increased risk of sustaining neurocognitive injuries, known as subconcussive blows, compared to non-contact sport athletes. We hypothesized that athletes participating in contact and limited contact sports, would exhibit a deficit in neurocognitive function following multiple seasons of play when compared to athletes participating in non-contact sports. Using a mixed repeated measures MANOVA statistical design, we analyzed computerized neurocognitive baseline ImPACT composite scores (verbal memory, visual memory, visual …

Readiness For Antimicrobial Resistance (Amr) Surveillance In Pakistan; A Model For Laboratory Strengthening, Dania Khalid Saeed, Rumina Hasan, Mahwish Naim, Afia Zafar, Erum Khan, Kauser Jabeen, Seema Irfan, Imran Ahmed Haq, Mohammad Zeeshan, Zabin Wajidali, Joveria Farooqi, Sadia Shakoor, Abdul Chagla, Jason Roy

Department of Pathology and Laboratory Medicine

Background: Limited capacity of laboratories for antimicrobial susceptibility testing (AST) presents a critical diagnostic bottleneck in resource limited countries. This paper aims to identify such gaps and to explore whether laboratory networks could contribute towards improving AST in low resource settings.
Methods: A self-assessment tool to assess antimicrobial susceptibility testing capacity was administered as a pre-workshop activity to participants from 30 microbiology laboratories in 3 cities in Pakistan. Data from public and private laboratories was analyzed and capacity of each scored in percentage terms. Laboratories from Karachi were invited to join a support network. A cohort of five laboratories that …

Therapeutic Uses Of Pineapple-Extracted Bromelain In Surgical Care - A Review., Zehra Abdul Muhammad, Tashfeen Ahmad

Department of Surgery Docs

Abstract

Bromelain is an extract obtained from the pineapple plant and is used as a traditional folk remedy for several ailments. In this review, a comprehensive electronic database search was carried out to compile available literature on therapeutic implications of bromelain. Pharmaceutical value of bromelain has been demonstrated in different surgical sub-specialties. Diverse biological processes like anti-inflammatory, anti-oedematous, analgesic, anti-thrombotic, exfoliation etc. are involved in bromelain's therapeutic actions, mediated through the kallikrein-kinin and arachidonic acid pathways as well as through effects on cell mediated immunity. Bromelain equals non-steroidal anti-inflammatory drugs as an anti-inflammatory agent, but has been shown to have …

Ambulatory Blood Pressure, Left Ventricular Hypertrophy, And Allograft Function In Children And Young Adults After Kidney Transplantation., Gilad Hamdani, Edward J. Nehus, Coral D. Hanevold, Judith Sebestyen Van Sickle, Robert Woroniecki, Scott E. Wenderfer, David K. Hooper, Douglas Blowey, Amy Wilson, Bradley A. Warady, Mark M. Mitsnefes

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Hypertension is a common complication and is an important risk factor for graft loss and adverse cardiovascular outcomes in pediatric kidney transplantation. Ambulatory blood pressure monitoring (ABPM) is the preferred method to characterize blood pressure status.

METHODS: We conducted a retrospective review of a large cohort of children and young adults with kidney transplant to estimate the prevalence of abnormal ambulatory blood pressure (ABP), assess factors associated with abnormal ABP, and examine whether ambulatory hypertension is associated with worse allograft function and left ventricular hypertrophy (LVH).

RESULTS: Two hundred twenty-one patients had ABPM, and 142 patients had echocardiographic results …

International Consensus (Icon) On: Clinical Consequences Of Mite Hypersensitivity, A Global Problem., Mario Sánchez-Borges, Enrique Fernandez-Caldas, Wayne R. Thomas, Martin D. Chapman, Bee Wah Lee, Luis Caraballo, Nathalie Acevedo, Fook Tim Chew, Ignacio J. Ansotegui, Leili Behrooz, Wanda Phipatanakul, Roy Gerth Van Wijk, Demoly Pascal, Nelson Rosario, Motohiro Ebisawa, Mario Geller, Santiago Quirce, Susanne Vrtala, Rudolf Valenta, Markus Ollert, Giorgio Walter Canonica, Moises A. Calderón, Charles S. Barnes, Adnan Custovic, Suwat Benjaponpitak, Arnaldo Capriles-Hulett

Manuscripts, Articles, Book Chapters and Other Papers

Since mite allergens are the most relevant inducers of allergic diseases worldwide, resulting in significant morbidity and increased burden on health services, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), formed by the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI), the European Academy of Allergy and Clinical Immunology (EAACI), and the World Allergy Organization (WAO), has proposed to issue an International Consensus (ICON) on the clinical consequences of mite hypersensitivity. The objectives of this document are to highlight aspects of mite biology that are clinically relevant, to update the …

Effects Of Conjugated Linoleic Acid And Metformin On Insulin Sensitivity In Obese Children: Randomized Clinical Trial, Nayely Garibay-Nieto, Gloria Queipo-García, Flor Alvarez, Mayra Bustos, Erendira Villanueva, Fernando Ramírez, Mireya León, Estibalitz Laresgoiti-Servitje, Juan Carlos Lopez Alvarenga, Ravi Duggirala

School of Medicine Publications

Context: Insulin resistance precedes metabolic syndrome abnormalities and may promote cardiovascular disease and type 2 diabetes in children with obesity. Results of lifestyle modification programs have been discouraging, and the use of adjuvant strategies has been necessary.

Objective: This study aimed to evaluate the effects of metformin and conjugated linoleic acid (CLA) on insulin sensitivity, measured via euglycemic-hyperinsulinemic clamp technique and insulin pathway expression molecules in muscle biopsies of children with obesity.

Design: A randomized, double-blinded, placebo-controlled clinical trial was conducted.

Setting: Children with obesity were randomly assigned to receive metformin, CLA, or placebo.

Results: Intervention had a …

Slc11a1 Polymorphisms And Host Susceptibility To Cutaneous Leishmaniasis In Pakistan., Mariam Sophie,, Abdul L Hameed Institute Of Biomedical And Genetic Engineering (Ibge), 24-Mauve Area, G- 9/1, Islamabad, Pakistan., Akhtar Muneer, Azam J. Samdani, Saima Saleem, Abid Azhar

Department of Medicine

Background:The vector-borne cutaneous leishmaniasis (CL) is endemic in several regions of Pakistan mainly affecting poor populations. Host genetic factors, particularly SLC11A1 (solute carrier transmembrane protein) within macrophages, play a crucial role in disease pathology and susceptibility. Association of SLC11A1 with cutaneous leishmaniasis, a neglected tropical disease, is not well established. Inconsistencies have been observed within different populations worldwide with respect to genetic susceptibility. This study was designed to investigate genetic variation(s) in SLC11A1 and to assess possible association with cutaneous leishmaniasis in Pakistan.

Results: Eight polymorphisms (rs2276631, rs3731864, rs2290708, rs2695342, rs201565523, rs17215556, rs17235409, rs17235416) were genotyped across SLC11A1 in …

Ion Channel Expression Patterns In Glioblastoma Stem Cells With Functional And Therapeutic Implications For Malignancy., Julia Pollak, Karan G Rai, Cory C Funk, Sonali Arora, Eunjee Lee, Jun Zhu, Nathan D Price, Patrick J Paddison, Jan-Marino Ramirez, Robert C Rostomily

Articles, Abstracts, and Reports

Ion channels and transporters have increasingly recognized roles in cancer progression through the regulation of cell proliferation, migration, and death. Glioblastoma stem-like cells (GSCs) are a source of tumor formation and recurrence in glioblastoma multiforme, a highly aggressive brain cancer, suggesting that ion channel expression may be perturbed in this population. However, little is known about the expression and functional relevance of ion channels that may contribute to GSC malignancy. Using RNA sequencing, we assessed the enrichment of ion channels in GSC isolates and non-tumor neural cell types. We identified a unique set of GSC-enriched ion channels using differential expression …

Management Of Simultaneous Bilateral Femur Fractures In A Tertiary Care Hospital: A Retrospective Review, Masood Umer, Syed Zohaib Gulzar Naqvi, Raza Askari, Umair Ashraf

Department of Surgery Docs

Abstract: Introduction: Bilateral long bone fractures are rare and usually are associated with increased risk of complications. These fractures are usually associated with poly traumatic injuries or high impact trauma resulting in shock. Commonest etiology is road traffic accident. Closed diaphyseal fractures are best managed by intramedullary nailing; management becomes difficult if there are open fractures and late arrival. In this study we intend to present our experience of managing these patients. Materials and Methods: Medical records of all adult patients (age more than 16 years of age) admitted at Aga Khan University and Hospital with bilateral femur fractures +/- …

Bowled Over By Cricket: Impact Of Tape-Ball Injuries On The Eyes, Salman Naveed Sadiq, Azam Ali, Bushra Usmani, Khabir Ahmed

Department of Surgery Docs

Abstract

PURPOSE:

The aim of this study was to describe the type and severity of tape-ball cricket-related eye injuries seen at a tertiary care hospital.

DESIGN:

A descriptive case series.

METHODS:

This study included all cases of tape-ball cricket-related eye injuries presenting to the Section of Ophthalmology, Aga Khan University Hospital, Karachi, from January 2014 to January 2015.

RESULTS:

A total of 20 patients with tape-ball cricket-related eye injuries were treated during this period. The right eye was involved in most (14/20) of the cases. The commonest presenting symptoms included reduced/blurred vision, ocular pain, redness, and floaters. Sixty percent (12/20) …

High Levels Of Iron Supplementation Prevents Neural Tube Defects In The Fpn1(Ffe) Mouse Model., Bethany A Stokes, Julia A Sabatino, Irene E. Zohn

Pediatrics Faculty Publications

BACKGROUND: Periconception maternal nutrition and folate in particular are important factors influencing the incidence of neural tube defects (NTDs). Many but not all NTDs are prevented by folic acid supplementation and there is a pressing need for additional strategies to prevent these birth defects. Other micronutrients such as iron are potential candidates, yet a clear role for iron deficiency in contributing to NTDs is lacking. Our previous studies with the flatiron (ffe) mouse model of Ferroportin1 (Fpn1) deficiency suggest that iron is required for neural tube closure and forebrain development raising the possibility that iron supplementation could prevent NTDs.

METHODS: …

Rna Sequencing Reveals A Role Of Tonebp Transcription Factor In Regulation Of Pro-Inflammatory Genes In Response To Hyperosmolarity In Healthy Nucleus Pulposus Cells: A Homeostatic Response?, Zariel I. Johnson, Irving M. Shapiro, Makarand V. Risbud

Department of Orthopaedic Surgery Faculty Papers

Transcription factor tonicity-responsive enhancer-binding protein (TonEBP/NFAT5) is critical for osmo-adaptation and extracellular matrix homeostasis of nucleus pulposus (NP) cells in their hypertonic tissue niche. Recent studies implicate TonEBP signaling in inflammatory disease and rheumatoid arthritis pathogenesis. However, broader functions of TonEBP in the disc remain unknown. RNA sequencing was performed on NP cells with TonEBP knockdown under hypertonic conditions. 1140 TonEBP-dependent genes were identified and categorized using Ingenuity Pathway Analysis. Bioinformatic analysis showed enrichment of matrix homeostasis and cytokine/chemokine signaling pathways. C-C motif chemokine ligand 2 (CCL2), interleukin 6 (IL6), tumor necrosis factor (TNF), and nitric oxide synthase 2 (NOS2) …

Vamorolone, A Dissociative Steroidal Compound, Reduces Pro-Inflammatory Cytokine Expression In Glioma Cells And Increases Activity And Survival In A Murine Model Of Cortical Tumor., Elizabeth Wells, Madhuri Kambhampati, Jesse M Damsker, Heather Gordish-Dressman, Sridevi Yadavilli, Oren J Becher, Jamila Gittens, Mojca Stampar, Roger J. Packer, Javad Nazarian

Genomics and Precision Medicine Faculty Publications

Corticosteroids, such as dexamethasone, are routinely used as palliative care in neuro-oncology for their anti-inflammatory benefits, however many patients experience dose limiting side effects caused by glucocorticoid response element (GRE)-mediated transcription. The purpose of this study was to use a murine model to investigate a new steroid alternative, vamorolone, which promises to reduce side effects through dissociating GRE-mediated transcription and NF-κB -mediated anti-inflammatory actions. To compare vamorolone to dexamethasone in reducing pro-inflammatory signals in vitro, murine glioma cells were treated with dexamethasone, vamorolone or vehicle control. Changes in mRNA expression were assessed using the nanostring inflammatory platform. Furthermore, drug …

Immunogenicity And Protective Efficacy Of The Dar-901 Booster Vaccine In A Murine Model Of Tuberculosis, Timothy Lahey, Dominick Laddy, Krystal Hill, Jacqueline Schaeffer

Dartmouth Scholarship

The development of a novel tuberculosis vaccine is a leading global health priority. SRL172, an inactivated, whole-cell mycobacterial vaccine, was safe, immunogenic and reduced the incidence of culture-confirmed tuberculosis in a phase III trial in HIV-infected and BCG immunized adults in Tanzania. Here we describe the immunogenicity and protective efficacy of DAR-901, a booster vaccine against tuberculosis manufactured from the same seed strain using a new scalable method.

Sirt1 Regulates Glial Progenitor Proliferation And Regeneration In White Matter After Neonatal Brain Injury., Beata Jablonska, Marcin Gierdalski, Li-Jin Chew, Teresa Hawley, Mackenzie Catron, Arturo Lichauco, Juan Cabrera-Luque, Tracy Yuen, David Rowitch, Vittorio Gallo

Pediatrics Faculty Publications

Regenerative processes in brain pathologies require the production of distinct neural cell populations from endogenous progenitor cells. We have previously demonstrated that oligodendrocyte progenitor cell (OPC) proliferation is crucial for oligodendrocyte (OL) regeneration in a mouse model of neonatal hypoxia (HX) that reproduces diffuse white matter injury (DWMI) of premature infants. Here we identify the histone deacetylase Sirt1 as a Cdk2 regulator in OPC proliferation and response to HX. HX enhances Sirt1 and Sirt1/Cdk2 complex formation through HIF1α activation. Sirt1 deacetylates retinoblastoma (Rb) in the Rb/E2F1 complex, leading to dissociation of E2F1 and enhanced OPC proliferation. Sirt1 knockdown in culture …

Advances And Perspectives In Genetics Of Congenital Thyroid Disorders Associated With Thyroglobulin Gene Mutations, Héctor M. Targovnik, Cintia E. Citterio, Sofi Siffo, Carina M. Rivolta

Pharmacy Faculty Articles and Research

Dyshormonogenesis due to thyroglobulin (TG) gene mutations is a rare cause of congenital hypothyroidism with an estimated incidence of approximately 1 in 100,000 newborns. The TG gene is organized in 48 exons, spanning over 270 kb on human chromosome 8q24. The human TG mRNA is 8.5 Kb long and the preprotein monomer is composed of a 19 amino acids signal peptide followed by a 2749 residues polypeptide. Until now, one hundred seventeen deleterious mutations in the human TG gene have been identified and characterized, originating structural changes in the protein that alter the normal protein folding, assembly and …