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Articles 1 - 30 of 60
Full-Text Articles in Medical Biochemistry
Goblet Cell Carcinoma Of The Appendix: A Case Report On Goblet Cell Carcinoid, Sheliza Kabani, Aubtin Saedi, Austin Lehr, Lina O'Brien
Goblet Cell Carcinoma Of The Appendix: A Case Report On Goblet Cell Carcinoid, Sheliza Kabani, Aubtin Saedi, Austin Lehr, Lina O'Brien
HCA Healthcare Journal of Medicine
Goblet cell carcinoid of the appendix is a rare neoplasm with histological features of both neuroendocrine and adenocarcinomas. The combination of its aggressive behavior, infrequent occurrence, and variable clinical presentation convolutes the management of this tumor. We report the case of a 75-year-old female presenting with acute appendicitis. A laparoscopic appendectomy was performed. The pathology report showed goblet cell carcinoid at the base of the appendix with involvement of the proximal surgical margins. At her postoperative visit, the patient’s pathology report and options for management were reviewed, and the patient agreed to proceed with a right hemicolectomy 8-10 weeks after …
Purification And Use Of Trna For Enzymatic Post-Translational Addition Of Amino Acids To Proteins., Irem Avcilar-Kucukgoze, Howard Gamper, Ya-Ming Hou, Anna Kashina
Purification And Use Of Trna For Enzymatic Post-Translational Addition Of Amino Acids To Proteins., Irem Avcilar-Kucukgoze, Howard Gamper, Ya-Ming Hou, Anna Kashina
Department of Biochemistry and Molecular Biology Faculty Papers
Post-translational addition of amino acids to proteins by enzymes using aminoacyl-tRNA is an emerging regulatory mechanism. Examples include Arg transfer in eukaryotes, Leu/Phe transfer in bacteria, and tRNA-synthetase-mediated addition of amino acids to Lys side chains. Here, we present a method of purification and use of tRNA for such reactions, focusing on tRNAArg and its use for arginylation. This method can also be used for other tRNA-mediated reactions. For complete details on the use and execution of this protocol, please refer to Avcilar-Kucukgoze et al. (2020).
Impact Of Endangered Animal Protection Rights, Policies, And Practices On Zoonotic Disease Spread, Daniella Fedak-Lengel
Impact Of Endangered Animal Protection Rights, Policies, And Practices On Zoonotic Disease Spread, Daniella Fedak-Lengel
Honors Projects
Building on field research in Costa Rica and Belize, this honors project analyzes environmental and endangered animal protection policies, rights, and practices in Central America and the Caribbean, and assesses the impact of veterinary science and biological research and practice, particularly conservation biology, on animal welfare concerns. Informed by the recent surge in awareness regarding zoonoses and zoonotic disease transmission, prevention and control, resulting from the current global pandemic of SARS-CoV-2, the project assesses the need for new and innovative types of collaboration, particularly involving conservation biologists, environmental scientists, public health experts, law and policy makers, and global trade and …
Design Of Hfgf1 Variant(S) With Increased Stability And Enhanced Bioactivity, Shilpi P. Agrawal
Design Of Hfgf1 Variant(S) With Increased Stability And Enhanced Bioactivity, Shilpi P. Agrawal
Graduate Theses and Dissertations
Fibroblast growth factors (FGFs) are involved in various cellular processes such as cell growth,proliferation, differentiation, migration, angiogenesis, wound healing and embryonic development. Human acidic fibroblast growth factor (hFGF1) binds non-selectively to all the four FGF-receptors and is therefore considered as a powerful mitogen with broadest specificity. However, pharmacological applications of hFGF1 are restricted due to the low thermal stability of the growth factor. hFGF1 has low thermodynamic stability under physiological temperatures which leads to impairment of cellular signaling process thereby preventing its potential mitogenic properties. hFGF1 has a heparin binding pocket at the C-terminus which comprises of positively charges residues. …
The Role Of Liver Sinusoidal Endothelial Cells In Liver Malady Homeostasis, Fatima Cabral
The Role Of Liver Sinusoidal Endothelial Cells In Liver Malady Homeostasis, Fatima Cabral
Department of Biochemistry: Dissertations, Theses, and Student Research
Current literature described techniques for the purification of liver cell types through text alone. The techniques described for the isolation of liver sinusoidal endothelial cells as well as hepatocytes described here are modified from a published article in the Journal of Visualized experiments. The video protocol allows for the user to successfully isolate cells as the most difficult parts of the procedure are demonstrated visually. The detection of liver maladies such as the non-alcoholic fatty liver disease, the stage if this disease and differentiation between non-alcoholic and alcoholic fatty liver disease is demonstrated in the development of a unique panel …
Hyperpolarized Carbon-13 Magnetic Resonance Measurements Of Tissue Perfusion And Metabolism, Keith Michel
Hyperpolarized Carbon-13 Magnetic Resonance Measurements Of Tissue Perfusion And Metabolism, Keith Michel
Dissertations and Theses (Open Access)
Hyperpolarized Magnetic Resonance Imaging (HP MRI) is an emerging modality that enables non-invasive interrogation of cells and tissues with unprecedented biochemical detail. This technology provides rapid imaging measurements of the activity of a small quantity of molecules with a strongly polarized nuclear magnetic moment. This polarization is created in a polarizer separate from the imaging magnet, and decays continuously towards a non-detectable thermal equilibrium once the imaging agent is removed from the polarizer and administered by intravenous injection. Specialized imaging strategies are therefore needed to extract as much information as possible from the HP signal during its limited lifetime.
In …
Great Expectations: Phosph(On)Ate Prodrugs In Drug Design—Opportunities And Limitations, Victoria Yan
Great Expectations: Phosph(On)Ate Prodrugs In Drug Design—Opportunities And Limitations, Victoria Yan
Dissertations and Theses (Open Access)
Phosphate and phosphonates are chemical moieties with historical precedence in anticancer and antiviral nucleotide analogues. Synchronous to modern efforts identifying novel therapeutic targets in cancer, such chemical moieties are being investigated in the design of novel inhibitors with antineoplastic potential. A central challenge to the delivery of phosph(on)ate-containing drugs is their anionic character at physiological pH, which portends poor membrane permeability. This limitation has been successfully overcome through the use of prodrugs. When attached to the phosph(on)ate moiety, prodrugs mask the negative charge and easily enable cell permeability. Upon cellular entry, the promoieties are enzymatically or environmentally cleaved to unveil …
Role For Carbohydrate Response Element-Binding Protein (Chrebp) In High Glucose-Mediated Repression Of Long Noncoding Rna Tug1, Jianyin Long, Daniel L Galvan, Koki Mise, Yashpal S Kanwar, Li Li, Naravat Poungavrin, Paul A Overbeek, Benny H Chang, Farhad R Danesh
Role For Carbohydrate Response Element-Binding Protein (Chrebp) In High Glucose-Mediated Repression Of Long Noncoding Rna Tug1, Jianyin Long, Daniel L Galvan, Koki Mise, Yashpal S Kanwar, Li Li, Naravat Poungavrin, Paul A Overbeek, Benny H Chang, Farhad R Danesh
Faculty, Staff and Students Publications
Long noncoding RNAs (lncRNAs) have been shown to play key roles in a variety of biological activities of the cell. However, less is known about how lncRNAs respond to environmental cues and what transcriptional mechanisms regulate their expression. Studies from our laboratory have shown that the lncRNA Tug1 (taurine upregulated gene 1) is crucial for the progression of diabetic kidney disease, a major microvascular complication of diabetes. Using a combination of proximity labeling with the engineered soybean ascorbate peroxidase (APEX2), ChIP-qPCR, biotin-labeled oligonucleotide pulldown, and classical promoter luciferase assays in kidney podocytes, we extend our initial observations in the current …
Polydopamine Antioxidant Hydrogels For Wound Healing Applications, Naphtali A. O'Connor, Abdulhaq Syed, Madeline Wong, Josiah Hicks, Greisly Nunez, Andrei Jitianu, Zach Siler, Marnie Peterson
Polydopamine Antioxidant Hydrogels For Wound Healing Applications, Naphtali A. O'Connor, Abdulhaq Syed, Madeline Wong, Josiah Hicks, Greisly Nunez, Andrei Jitianu, Zach Siler, Marnie Peterson
Publications and Research
Antioxidants are known to improve the wound healing process and are researched as a therapeutic strategy to treat chronic wounds. Dopamine is a known neurotransmitter with antioxidant properties that can be polymerized to form polydopamine (PDA). Herein, polydopamine is demonstrated as an antioxidant biomaterial. In prior work, we developed methodology to prepare hydrogels by crosslinking polysaccharides with polyamines via epichlorohydrin and NaOH. Using this previously developed methodology, dextran hydrogels crosslinked with polydopamine were prepared. Darkening of the gels indicated the increasing incorporation of polydopamine within the hydrogels. In addition to basic pH, polydopamine can be formed by reaction with polyethylene …
Bioavailability And Spatial Distribution Of Fatty Acids In The Rat Retina After Dietary Omega-3 Supplementation, Elisa Vidal, Bokkyoo Jun, William C. Gordon, Marie Annick Maire, Lucy Martine, Stéphane Grégoire, Spiro Khoury, Stephanie Cabaret, Olivier Berdeaux, Niyazi Acar, Lionel Bretillon, Nicolas G. Bazan
Bioavailability And Spatial Distribution Of Fatty Acids In The Rat Retina After Dietary Omega-3 Supplementation, Elisa Vidal, Bokkyoo Jun, William C. Gordon, Marie Annick Maire, Lucy Martine, Stéphane Grégoire, Spiro Khoury, Stephanie Cabaret, Olivier Berdeaux, Niyazi Acar, Lionel Bretillon, Nicolas G. Bazan
School of Medicine Faculty Publications
Spatial changes of FAs in the retina in response to different dietary n-3 formulations have never been explored, although a diet rich in EPA and DHA is recommended to protect the retina against the effects of aging. In this study, Wistar rats were fed for 8 weeks with balanced diet including either EPA-containing phospholipids (PLs), EPA-containing TGs, DHA-containing PLs, or DHA-containing TGs. Qualitative changes in FA composition of plasma, erythrocytes, and retina were evaluated by gas chromatography-flame ionization detector. Following the different dietary intakes, changes to the quantity and spatial organization of PC and PE species in retina were determined …
Characterization Of The 5′-Flanking Region Of The Human And Mouse Chac1 Genes, Yuki Nomura, Charity F. Sylvester, Lisa O. Nguyen, Mahmoud Kandeel, Yoko Hirata, Imran N. Mungrue, Kentaro Oh-Hashi
Characterization Of The 5′-Flanking Region Of The Human And Mouse Chac1 Genes, Yuki Nomura, Charity F. Sylvester, Lisa O. Nguyen, Mahmoud Kandeel, Yoko Hirata, Imran N. Mungrue, Kentaro Oh-Hashi
School of Medicine Faculty Publications
The Unfolded Protein Response pathway is a conserved signaling mechanism having important roles in cellular physiology and is perturbed accompanying disease. We previously identified the novel UPR target gene CHAC1, a direct target of ATF4, downstream of PERK-EIF2A and activated by the UPR pathway. CHAC1 enzyme directs catalysis of γ-linked glutamate bonds within specific molecular targets. CHAC1 is the first enzyme characterized that can catalyze intracellular glutathione degradation in eukaryotes, having implications for regulation of oxidative stress. DDIT3 (CHOP) is a terminal UPR transcription factor, regulated by ATF4 and an output promoting cell death signaling. Herein we examine the relationship …
Blocking C-Met/Erbb1 Axis Prevents Brain Metastasis In Erbb2+ Breast Cancer, Shailendra K. Gautam, Ranjana K. Kanchan, Jawed A. Siddiqui, Shailendra K. Maurya, Sanchita Rauth, Naveenkumar Perumal, Pranita Atri, Ramakanth C. Venkata, Kavita Mallya, Sameer Mirza, Moorthy P. Ponnusamy, Vimla Band, Sidharth Mahapatra, Maneesh Jain, Surinder K. Batra, Mohd W. Nasser
Blocking C-Met/Erbb1 Axis Prevents Brain Metastasis In Erbb2+ Breast Cancer, Shailendra K. Gautam, Ranjana K. Kanchan, Jawed A. Siddiqui, Shailendra K. Maurya, Sanchita Rauth, Naveenkumar Perumal, Pranita Atri, Ramakanth C. Venkata, Kavita Mallya, Sameer Mirza, Moorthy P. Ponnusamy, Vimla Band, Sidharth Mahapatra, Maneesh Jain, Surinder K. Batra, Mohd W. Nasser
Journal Articles: Biochemistry & Molecular Biology
Brain metastasis (BrM) remains a significant cause of cancer-related mortality in epidermal growth factor receptor 2-positive (ERBB2+) breast cancer (BC) patients. We proposed here that a combination treatment of irreversible tyrosine kinase inhibitor neratinib (NER) and the c-MET inhibitor cabozantinib (CBZ) could prevent brain metastasis. To address this, we first tested the combination treatment of NER and CBZ in the brain-seeking ERBB2+ cell lines SKBrM3 and JIMT-1-BR3, and in ERBB2+ organoids that expressed the c-MET/ERBB1 axis. Next, we developed and characterized an orthotopic mouse model of spontaneous BrM and evaluated the therapeutic effect of CBZ and …
Validation And Application Of A Novel Target-Based Whole-Cell Screen To Identify Antifungal Compounds, Christian Alexander Dejarnette
Validation And Application Of A Novel Target-Based Whole-Cell Screen To Identify Antifungal Compounds, Christian Alexander Dejarnette
Theses and Dissertations (ETD)
Traditional approaches to drug discovery are inefficient and have several key limitations that constrain our capacity to rapidly identify and develop novel experimental therapeutics. To address this, we have devised a second-generation target-based whole-cell screening assay based on the principles of competitive fitness, which can rapidly identify target-specific and physiologically-active compounds. Briefly, strains expressing high, intermediate, and low levels of a preselected target protein were constructed, tagged with spectrally distinct fluorescent proteins (FPs), and mixed together. The pooled strains were then grown in the presence of various small molecules, and the relative growth of each strain within the mixed culture …
Design And Synthesis Of Core–Shell Microgels With One‐Step Clickable Crosslinked Cores And Ultralow Crosslinked Shells, Molla R. Islam, Chelsea Nguy, Sanika Pandit, L. Andrew Lyon
Design And Synthesis Of Core–Shell Microgels With One‐Step Clickable Crosslinked Cores And Ultralow Crosslinked Shells, Molla R. Islam, Chelsea Nguy, Sanika Pandit, L. Andrew Lyon
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
The present study is conducted to explore the engineering of core–shell microgels such that the core can be rapidly labeled with a variety of fluorophores, while the shell retains the softness needed in specific biomedical applications. Azide containing crosslinked core particles based on a crosslinked poly(N‐isopropylacrylamide) particle, using a one‐pot, multistep polymerization is synthesized. A core–shell microgel is then synthesized by growing a crosslinker‐free poly(N‐isopropylacrylamide)‐co‐acrylic acid (ULC10AAc) shell through a two‐step seed and feed polymerization. A simple “click” reaction between the azide present on the core and dibenzocyclooctyne containing fluorophores to make dyed core–shell …
Acinar Transformed Ductal Cells Exhibit Differential Mucin Expression In A Tamoxifen-Induced Pancreatic Ductal Adenocarcinoma Mouse Model, Kavita Mallya, Dhanya Haridas, Parthasarathy Seshacharyulu, Ramesh Pothuraju, Wade M. Junker, Shiv Ram Krishn, Sakthivel Muniyan, Raghupathy Vengoji, Surinder K. Batra, Satyanarayana Rachagani
Acinar Transformed Ductal Cells Exhibit Differential Mucin Expression In A Tamoxifen-Induced Pancreatic Ductal Adenocarcinoma Mouse Model, Kavita Mallya, Dhanya Haridas, Parthasarathy Seshacharyulu, Ramesh Pothuraju, Wade M. Junker, Shiv Ram Krishn, Sakthivel Muniyan, Raghupathy Vengoji, Surinder K. Batra, Satyanarayana Rachagani
Journal Articles: Biochemistry & Molecular Biology
Pancreatic cancer (PC) is acquired postnatally; to mimic this scenario, we developed an inducible KrasG12D; Ptf1a-CreER™ (iKC) mouse model, in which Kras is activated postnatally at week 16 upon tamoxifen (TAM) administration. Upon TAM treatment, iKC mice develop pancreatic intraepithelial neoplasia (PanIN) lesions and PC with metastasis at the fourth and fortieth weeks, respectively, and exhibited acinar-to-ductal metaplasia (ADM) and transdifferentiation. Kras activation upregulated the transcription factors Ncoa3, p-cJun and FoxM1, which in turn upregulated expression of transmembrane mucins (Muc1, Muc4 and Muc16) and secretory mucin (Muc5Ac). Interestingly, knockdown of KrasG12D in multiple PC cell lines resulted …
Mitochondrial Oxidative And Nitrosative Stress And Alzheimer Disease, D. Allan Butterfield, Debra Boyd-Kimball
Mitochondrial Oxidative And Nitrosative Stress And Alzheimer Disease, D. Allan Butterfield, Debra Boyd-Kimball
Chemistry Faculty Publications
Oxidative and nitrosative stress are widely recognized as critical factors in the pathogenesis and progression of Alzheimer disease (AD) and its earlier stage, amnestic mild cognitive impairment (MCI). A major source of free radicals that lead to oxidative and nitrosative damage is mitochondria. This review paper discusses oxidative and nitrosative stress and markers thereof in the brain, along with redox proteomics, which are techniques that have been pioneered in the Butterfield laboratory. Selected biological alterations in—and oxidative and nitrosative modifications of—mitochondria in AD and MCI and systems of relevance thereof also are presented. The review article concludes with a section …
Characterization Of Retinal Biomechanical Properties Using Brillouin Microscopy, Yogeshwari S Ambekar, Manmohan Singh, Giuliano Scarcelli, Elda M Rueda, Benjamin M Hall, Ross A Poché, Kirill V Larin
Characterization Of Retinal Biomechanical Properties Using Brillouin Microscopy, Yogeshwari S Ambekar, Manmohan Singh, Giuliano Scarcelli, Elda M Rueda, Benjamin M Hall, Ross A Poché, Kirill V Larin
Faculty, Staff and Students Publications
SIGNIFICANCE: The retina is critical for vision, and several diseases may alter its biomechanical properties. However, assessing the biomechanical properties of the retina nondestructively is a challenge due to its fragile nature and location within the eye globe. Advancements in Brillouin spectroscopy have provided the means for nondestructive investigations of retina biomechanical properties.
AIM: We assessed the biomechanical properties of mouse retinas using Brillouin microscopy noninvasively and showed the potential of Brillouin microscopy to differentiate the type and layers of retinas based on stiffness.
APPROACH: We used Brillouin microscopy to quantify stiffness of fresh and paraformaldehyde (PFA)-fixed retinas. As further …
Preclinical Studies On Intranasal Npy And Selective Npy Receptor Agonists In Rodent Ptsd Model: Focus On Locus Coeruleus Noradrenergic System, Chiso Nwokafor
Preclinical Studies On Intranasal Npy And Selective Npy Receptor Agonists In Rodent Ptsd Model: Focus On Locus Coeruleus Noradrenergic System, Chiso Nwokafor
NYMC Student Theses and Dissertations
Post-traumatic stress disorder (PTSD) is a debilitating psychological disorder that develops in a subset of individuals after exposure to a traumatic stress. Neuropeptide Y (NPY) an endogenous 36 amino acid neuropeptide expressed in many areas of the brain and periphery especially those involved in stress may confer resilience to the harmful effect of stress. We demonstrated changes in the Single Prolonged Stress (SPS) PTSD model and potential for their modulation by delivery of intranasal NPY to the brain. There was a progressive worsening of anxiety symptoms at two weeks compared to one week after SPS. Previously we showed that 150µg …
Capsaicin Is A Negative Allosteric Modulator Of The 5-Ht3 Receptor, Eslam El Nebrisi, Tatiana Prytkova, Dietrich Ernst Lorke, Luke Howarth, Asma Hassan Alzaabi, Keun-Hang Susan Yang, Frank Christopher Howarth, Murat Oz
Capsaicin Is A Negative Allosteric Modulator Of The 5-Ht3 Receptor, Eslam El Nebrisi, Tatiana Prytkova, Dietrich Ernst Lorke, Luke Howarth, Asma Hassan Alzaabi, Keun-Hang Susan Yang, Frank Christopher Howarth, Murat Oz
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
In this study, effects of capsaicin, an active ingredient of the capsicum plant, were investigated on human 5-hydroxytryptamine type 3 (5-HT3) receptors. Capsaicin reversibly inhibited serotonin (5-HT)-induced currents recorded by two-electrode voltage clamp method in Xenopus oocytes. The inhibition was time- and concentration-dependent with an IC50 = 62 μM. The effect of capsaicin was not altered in the presence of capsazepine, and by intracellular BAPTA injections or trans-membrane potential changes. In radio-ligand binding studies, capsaicin did not change the specific binding of the 5-HT3 antagonist [3H]GR65630, indicating that it is a noncompetitive inhibitor of …
Complete Chemical Structures Of Human Mitochondrial Trnas, Takeo Suzuki, Yuka Yashiro, Ittoku Kikuchi, Yuma Ishigami, Hironori Saito, Ikuya Matsuzawa, Shunpei Okada, Mari Mito, Shintaro Iwasaki, Ding Ma, Xuewei Zhao, Kana Asano, Huan Lin, Yohei Kirino, Yuriko Sakaguchi, Tsutomu Suzuki
Complete Chemical Structures Of Human Mitochondrial Trnas, Takeo Suzuki, Yuka Yashiro, Ittoku Kikuchi, Yuma Ishigami, Hironori Saito, Ikuya Matsuzawa, Shunpei Okada, Mari Mito, Shintaro Iwasaki, Ding Ma, Xuewei Zhao, Kana Asano, Huan Lin, Yohei Kirino, Yuriko Sakaguchi, Tsutomu Suzuki
Computational Medicine Center Faculty Papers
Mitochondria generate most cellular energy via oxidative phosphorylation. Twenty-two species of mitochondrial (mt-)tRNAs encoded in mtDNA translate essential subunits of the respiratory chain complexes. mt-tRNAs contain post-transcriptional modifications introduced by nuclear-encoded tRNA-modifying enzymes. They are required for deciphering genetic code accurately, as well as stabilizing tRNA. Loss of tRNA modifications frequently results in severe pathological consequences. Here, we perform a comprehensive analysis of post-transcriptional modifications of all human mt-tRNAs, including 14 previously-uncharacterized species. In total, we find 18 kinds of RNA modifications at 137 positions (8.7% in 1575 nucleobases) in 22 species of human mt-tRNAs. An up-to-date list of 34 …
Pharmacogenomics Cascade Testing (Phact): A Novel Approach For Preemptive Pharmacogenomics Testing To Optimize Medication Therapy, Don Roosan, Angela Hwang, Moom Roosan
Pharmacogenomics Cascade Testing (Phact): A Novel Approach For Preemptive Pharmacogenomics Testing To Optimize Medication Therapy, Don Roosan, Angela Hwang, Moom Roosan
Pharmacy Faculty Articles and Research
The implementation of pharmacogenomics (PGx) has come a long way since the dawn of utilizing pharmacogenomic data in clinical patient care. However, the potential benefits of sharing PGx results have yet to be explored. In this paper, we explore the willingness of patients to share PGx results, as well as the inclusion of family medication history in identifying potential family members for pharmacogenomics cascade testing (PhaCT). The genetic similarities in families allow for identifying potential gene variants prior to official preemptive testing. Once a candidate patient is determined, PhaCT can be initiated. PhaCT recognizes that further cascade testing throughout a …
Opioid Dependency And Its Effects On Alcohol Consumption, Emily V. Flores
Opioid Dependency And Its Effects On Alcohol Consumption, Emily V. Flores
Psychology and Counseling Theses
Previous research has found dualistic effects on alcohol consumption with low doses of buprenorphine increasing alcohol and higher doses of buprenorphine reducing alcohol consumption in rats (Ciccocioppo et al., 2006). Other existing research on naloxone treatment and alcohol consumption in opioid use has demonstrated that alcohol consumption decreases after naloxone treatment in rats (Hyytia & Sinclair, 1993). Yet, no research has been conducted on either rats or humans on the effects of buprenorphine and naloxone medication combined. The effects of opioid maintenance therapy are controversial and the relationship between alcohol consumption and opioid dependency treatment is mainly based on literature …
Cyclic Peptide-Gadolinium Nanoparticles For Enhanced Intracellular Delivery, Amir Nasrolahi Shirazi, Shang Eun Park, Shirin Rad, Luiza Baloyan, Dindyal Mandal, Muhammad Imran Sajid, Ryley Hall, Sandeep Lohan, Khalid Zoghebi, Keykavous Parang, Rakesh Tiwari
Cyclic Peptide-Gadolinium Nanoparticles For Enhanced Intracellular Delivery, Amir Nasrolahi Shirazi, Shang Eun Park, Shirin Rad, Luiza Baloyan, Dindyal Mandal, Muhammad Imran Sajid, Ryley Hall, Sandeep Lohan, Khalid Zoghebi, Keykavous Parang, Rakesh Tiwari
Pharmacy Faculty Articles and Research
A cyclic peptide containing one cysteine and five alternating tryptophan and arginine amino acids [(WR)5C] was synthesized using Fmoc/tBu solid-phase methodology. The ability of the synthesized cyclic peptide to produce gadolinium nanoparticles through an in situ one-pot mixing of an aqueous solution of GdCl3 with [(WR)5C] peptide solution was evaluated. Transmission electron microscopy showed the formed peptide-Gd nanoparticles in star-shape morphology with a size of ~250 nm. Flow cytometry investigation showed that the cellular uptake of a cell-impermeable fluorescence-labeled phosphopeptide (F′-GpYEEI, where F′ = fluorescein) was approximately six times higher in the presence of [(WR) …
The Bach1/Nrf2 Axis In Brain In Down Syndrome And Transition To Alzheimer Disease-Like Neuropathology And Dementia, Marzia Perluigi, Antonella Tramutola, Sara Pagnotta, Eugenio Barone, D. Allan Butterfield
The Bach1/Nrf2 Axis In Brain In Down Syndrome And Transition To Alzheimer Disease-Like Neuropathology And Dementia, Marzia Perluigi, Antonella Tramutola, Sara Pagnotta, Eugenio Barone, D. Allan Butterfield
Chemistry Faculty Publications
Down syndrome (DS) is the most common genetic cause of intellectual disability that is associated with an increased risk to develop early-onset Alzheimer-like dementia (AD). The brain neuropathological features include alteration of redox homeostasis, mitochondrial deficits, inflammation, accumulation of both amyloid beta-peptide oligomers and senile plaques, as well as aggregated hyperphosphorylated tau protein-containing neurofibrillary tangles, among others. It is worth mentioning that some of the triplicated genes encoded are likely to cause increased oxidative stress (OS) conditions that are also associated with reduced cellular responses. Published studies from our laboratories propose that increased oxidative damage occurs early in life in …
Ionophoric Polyphenols Are Permeable To The Blood Brain Barrier, Interact With Human Serum Albumin And Calf Thymus Dna, And Inhibit Ache Enzymatic Activity, Alberto Martinez, Mai Zahran, Miguel Gomez, Johnny Guevara, Rosemary Pichardo-Bueno, Junaid Asim, Gabriel Ortiz, Yaa Andoh, Sinji Shibutani, Baljit Kaur
Ionophoric Polyphenols Are Permeable To The Blood Brain Barrier, Interact With Human Serum Albumin And Calf Thymus Dna, And Inhibit Ache Enzymatic Activity, Alberto Martinez, Mai Zahran, Miguel Gomez, Johnny Guevara, Rosemary Pichardo-Bueno, Junaid Asim, Gabriel Ortiz, Yaa Andoh, Sinji Shibutani, Baljit Kaur
Publications and Research
Alzheimer’s disease (AD) is the most common form of dementia that affects more than 40 million people around the world. The incidence is expected to rapidly increase due to the lack of any effective treatment. In previous work we synthesized a family of five ionophoric polyphenols (compounds 1–5) that targeted important aspects related to AD, such as the toxic aggregation of amyloid-β peptides, the production of reactive oxygen species, or the excessive presence of Cu2+ ions. Here, in order to gain insights into their potential therapeutic value, we have tested the ability of compounds 1– …
Alcohol And Smoking Mediated Modulations In Adaptive Immunity In Pancreatitis, Rakesh Bhatia, Christopher Thompson, Koelina Ganguly, Shailender K. Singh, Surinder K. Batra, Sushil Kumar
Alcohol And Smoking Mediated Modulations In Adaptive Immunity In Pancreatitis, Rakesh Bhatia, Christopher Thompson, Koelina Ganguly, Shailender K. Singh, Surinder K. Batra, Sushil Kumar
Journal Articles: Biochemistry & Molecular Biology
Pancreatitis is a condition of pancreatic inflammation driven by injury to the pancreatic parenchyma. The extent of acinar insult, intensity, and type of immune response determines the severity of the disease. Smoking, alcohol and autoimmune pancreatitis are some of the predominant risk factors that increase the risk of pancreatitis by differentially influencing the adaptive immune system. The overall decrease in peripheral lymphocyte (T-, B- and (natural killer T-) NKT-cell) count and increased infiltration into the damaged pancreatic tissue highlight the contribution of adaptive immunity in the disease pathology. Smoking and alcohol modulate the responsiveness and apoptosis of T- and B-cells …
Mg2+-Dependent Methyl Transfer By A Knotted Protein: A Molecular Dynamics Simulation And Quantum Mechanics Study, Agata P Perlinska, Marcin Kalek, Thomas Christian, Ya-Ming Hou, Joanna I Sulkowska
Mg2+-Dependent Methyl Transfer By A Knotted Protein: A Molecular Dynamics Simulation And Quantum Mechanics Study, Agata P Perlinska, Marcin Kalek, Thomas Christian, Ya-Ming Hou, Joanna I Sulkowska
Department of Biochemistry and Molecular Biology Faculty Papers
Mg2+ is required for the catalytic activity of TrmD, a bacteria-specific methyltransferase that is made up of a protein topological knot-fold, to synthesize methylated m1G37-tRNA to support life. However, neither the location of Mg2+ in the structure of TrmD nor its role in the catalytic mechanism is known. Using molecular dynamics (MD) simulations, we identify a plausible Mg2+ binding pocket within the active site of the enzyme, wherein the ion is coordinated by two aspartates and a glutamate. In this position, Mg2+ additionally interacts with the carboxylate of a methyl donor cofactor S-adenosylmethionine (SAM). The computational results are validated by …
Lyssavirus Vaccine With A Chimeric Glycoprotein Protects Across Phylogroups, Christine R Fisher, David E Lowe, Todd G Smith, Yong Yang, Christina L Hutson, Christoph Wirblich, Gino Cingolani, Matthias J. Schnell
Lyssavirus Vaccine With A Chimeric Glycoprotein Protects Across Phylogroups, Christine R Fisher, David E Lowe, Todd G Smith, Yong Yang, Christina L Hutson, Christoph Wirblich, Gino Cingolani, Matthias J. Schnell
Department of Biochemistry and Molecular Biology Faculty Papers
Rabies is nearly 100% lethal in the absence of treatment, killing an estimated 59,000 people annually. Vaccines and biologics are highly efficacious when administered properly. Sixteen rabies-related viruses (lyssaviruses) are similarly lethal, but some are divergent enough to evade protection from current vaccines and biologics, which are based only on the classical rabies virus (RABV). Here we present the development and characterization of LyssaVax, a vaccine featuring a structurally designed, functional chimeric glycoprotein (G) containing immunologically important domains from both RABV G and the highly divergent Mokola virus (MOKV) G. LyssaVax elicits high titers of antibodies specific to both RABV …
Thrombospondin-1 Plays An Essential Role In Yes-Associated Protein Nuclear Translocation During The Early Phase Of Trypanosoma Cruzi Infection In Heart Endothelial Cells, Ashutosh Arun, Kayla J. Rayford, Ayorinde Cooley, Girish Rachakonda, Fernando Villalta, Siddharth Pratap, Maria F. Lima, Nader Sheibani, Pius N. Nde
Thrombospondin-1 Plays An Essential Role In Yes-Associated Protein Nuclear Translocation During The Early Phase Of Trypanosoma Cruzi Infection In Heart Endothelial Cells, Ashutosh Arun, Kayla J. Rayford, Ayorinde Cooley, Girish Rachakonda, Fernando Villalta, Siddharth Pratap, Maria F. Lima, Nader Sheibani, Pius N. Nde
Publications and Research
The protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease. This neglected tropical disease causes severe morbidity and mortality in endemic regions. About 30% of T. cruzi infected individuals will present with cardiac complications. Invasive trypomastigotes released from infected cells can be carried in the vascular endothelial system to infect neighboring and distant cells. During the process of cellular infection, the parasite induces host cells, to increase the levels of host thrombospondin-1 (TSP-1), to facilitate the process of infection. TSP-1 plays important roles in the functioning of vascular cells, including vascular endothelial cells with important implications in cardiovascular …
Sleep-Wake Disturbances In Mild Traumatic Brain Injury: Meta Analysis Of Literature And Modeling Of Cerebral Tissue Vulnerability, Xiangfu Zhang, Subhendra Sarkar, Mary A. Browne
Sleep-Wake Disturbances In Mild Traumatic Brain Injury: Meta Analysis Of Literature And Modeling Of Cerebral Tissue Vulnerability, Xiangfu Zhang, Subhendra Sarkar, Mary A. Browne
Publications and Research
Sleep disturbance is a frequent complaint for patients with mild traumatic brain injury (mTBI), it can prolong recovery, and the oxidative stress from lack of sleep could worsen other secondary damages of mTBI. The common types of sleep disturbance of mTBI include insomnia, daytime sleepiness, and obstructive sleep apnea. Conventional imaging often fails to detect any abnormalities in mTBI, and the etiology of sleep disturbance is still unclear. Based on the analysis of current published neurobiological and imaging literature, multiple factors could play a role leading to sleep disturbance in mTBI, however, we have focused on the diencephalon, melatonin and …