Medical Biochemistry Commons^™

Effect Of Hemiepiphysiodesis On The Growth Plate: The Histopathological Changes And Mechanism Exploration Of Recurrence In Mini Pig Model., Jing Ding, Jin He, Zhi-Qiang Zhang, Zhen-Kai Wu, Fang-Chun Jin

Manuscripts, Articles, Book Chapters and Other Papers

Purpose: Hemiepiphysiodesis has been widely used to correct angular deformity of long bone in immature patients. However, there is a limited knowledge about the biomechanical effect of this technique on the histopathological changes of the growth plate and the mechanism of recurrence of malformation after implant removal. We aimed to evaluate the biomechanical effect of hemiepiphysiodesis on the histopathological changes of the growth plate and the mechanism of recurrence of malformation after implant removal in Bama miniature pigs, and to explore the role of asymmetric stress during this procedure.

Methods: Eight 3-month-old male Bama miniature pigs sustained surgeries on the …

Characterization Of Cdk(5) Inhibitor, 20-223 (Aka Cp668863) For Colorectal Cancer Therapy, Caroline M. Robb, Smit Kour, Jacob I. Contreras, Ekta Agarwal, Carter J. Barger, Sandeep Rana, Yogesh Sonawane, Beth K. Neilsen, Margaret Taylor, Smitha Kizhake, Rhishikesh N. Thakare, Sanjib Chowdhury, Jing Wang, Jennifer D. Black, Michael A. Hollingsworth, Michael G. Brattain, Amarnath Natarajan

Journal Articles: Biochemistry & Molecular Biology

Colorectal cancer (CRC) remains one of the leading causes of cancer related deaths in the United States. Currently, there are limited therapeutic options for patients suffering from CRC, none of which focus on the cell signaling mechanisms controlled by the popular kinase family, cyclin dependent kinases (CDKs). Here we evaluate a Pfizer developed compound, CP668863, that inhibits cyclin-dependent kinase 5 (CDK5) in neurodegenerative disorders. CDK5 has been implicated in a number of cancers, most recently as an oncogene in colorectal cancers. Our lab synthesized and characterized CP668863 – now called 20-223. In our established colorectal cancer xenograft model, 20-223 reduced …

Pancreatic Cancer Associated With Obesity And Diabetes: An Alternative Approach For Its Targeting, Ramesh Pothuraju, Satyanarayana Rachagani, Wade M. Junker, Sanjib Chaudhary, Saraswathi Viswanathan, Sukhwinder Kaur, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Pancreatic cancer (PC) is among foremost causes of cancer related deaths worldwide due to generic symptoms, lack of effective screening strategies and resistance to chemo- and radiotherapies. The risk factors associated with PC include several metabolic disorders such as obesity, insulin resistance and type 2 diabetes mellitus (T2DM). Studies have shown that obesity and T2DM are associated with PC pathogenesis; however, their role in PC initiation and development remains obscure.

MAIN BODY: Several biochemical and physiological factors associated with obesity and/or T2DM including adipokines, inflammatory mediators, and altered microbiome are involved in PC progression and metastasis albeit by different …

Systems Biology Of Human Cells Responded To Influenza B Virus Infection, Kritsada Sirivassanametha

Chulalongkorn University Theses and Dissertations (Chula ETD)

Influenza B virus is a member of Orthomyxoviridae family which can cause influenza in human and affect to worldwide health problem. Systems biology is the computational modeling of molecular systems which is useful to predict how these biological systems change over time and under different conditions. In this study the multiomics was used to study human cellular response to influenza B virus infection. The transcriptome including mRNAs, lncRNAs and miRNAs and proteome were investigated by high-throughput technologies such as next-generation sequencing and mass spectrometry. The results showed that in human cells infected with influenza B virus, transcriptome including mRNAs, lncRNAs …

The Effect Of Dna Methylation On Tp73 Expression In Tumorgenesis, Nujuma A. Moussa

UROP Posters

Abstract: The Effect of DNA Methylation on TP73 Expression in Tumorgenesis

Nujuma Moussa, Zhixing Yao, Zaki A. Sherif

Department of Biochemistry & Molecular Biology, Howard University College of Medicine

TP73 is a member of the TP53 family of proteins that acts as a transcription factor to help regulate cellular distress. This tumor protein may play a dual role as a tumor suppressor and tumor promoter. The TP73 gene is mapped to chromosome 1p36, a frequently deleted region in neuroblastoma and other types of tumors. While mutations in the TP53 gene are commonly known to cause noxious cancers, 30% of cancers …

Cone Phosphodiesterase-6Γ’ Subunit Augments Cone Pde6 Holoenzyme Assembly And Stability In A Mouse Model Lacking Both Rod And Cone Pde6 Catalytic Subunits, Wen-Tao Deng, Saravanan Kolandaivelu, Astra Dinculescu, Jie Li, Ping Zhu, Vince A. Chiodo, Visvanathan Ramamurthy, William W. Hauswirth

Faculty & Staff Scholarship

Rod and cone phosphodiesterase 6 (PDE6) are key effector enzymes of the vertebrate phototransduction pathway. Rod PDE6 consists of two catalytic subunits PDE6α and PDE6β and two identical inhibitory PDE6γ subunits, while cone PDE6 is composed of two identical PDE6α’ catalytic subunits and two identical cone-specific PDE6γ’ inhibitory subunits. Despite their prominent function in regulating cGMP levels and therefore rod and cone light response properties, it is not known how each subunit contributes to the functional differences between rods and cones. In this study, we generated an rd10/cpfl1 mouse model lacking rod PDE6β and cone PDE6α’ subunits. Both rod and …

B-Cell Activating Factor As An Immunological Marker Of Disease Outcome And Treatment Response In Patients With Chronic Hepatitis B Virus Infection, Apichaya Khlaiphuengsin

Chulalongkorn University Theses and Dissertations (Chula ETD)

B-cell activating factor (BAFF), an important cytokine for B lymphocyte activation that implicated in the pathogenesis and disease progression chronic hepatitis B (CHB) patients. This study aimed at evaluating clinical correlation and prognostic role of plasma BAFF, BAFF receptor and related polymorphisms in patients with CHB undergoing pegylated interferon (peg-IFN) treatment and HBV-related hepatocellular carcinoma (HCC). This study shown that BAFF levels were elevated during treatment but decreased to pre-treatment levels after peg-IFN cessation in HBeAg-positive CHB patients. Patients with HCC had significantly higher BAFF levels compared with the non-HCC group and healthy controls. Moreover, the frequency of rs9514828 CT+TT …

Alternative Splicing Of Cytoplasmic Polyadenylation Element Binding Protein 2 Is Modulated Via Serine Arginine Splicing Factor 3 In Cancer Metastasis, James T. Deligio, James Thomas Deligio

Theses and Dissertations

Our laboratory delineated a role for alternative pre-mRNA splicing (AS) in triple negative breast cancer (TNBC). We found the translational regulator cytosolic polyadenylation element binding protein 2 (CPEB2) which has two isoforms, CPEB2A and CPEB2B, is alternatively spliced during acquisition of anoikis resistance (AnR) and metastasis. The splicing event which determines the CPEB2 isoform is via inclusion/ exclusion of exon four in the mature mRNA transcript. The loss of CPEB2A with a concomitant increase in CPEB2B is required for TNBC cells to metastasize in vivo. We examined RNAseq profiles of TNBC cells which had CPEB2 isoforms specifically downregulated to …

Understanding The Role Of Phosphoinositide 3-Kinase And Its Function As A Driving Force Behind The Er Stress Response In Fibrostenotic Crohn’S Disease-Affected Ileal Smooth Muscle Cells, Prashant Yadav

Theses and Dissertations

Crohn’s disease (CD) affects about 780,000 people in the United States alone, and it is estimated that 6-15 per 100,000 persons will receive a diagnosis of this disease each year. There currently is no cure for Crohn’s disease, and available medical therapies simply serve to alleviate the inflammation. This does not help treat fibrostenosis that Crohn’s disease patients may develop, which can only be treated surgically. Finding alternatives to treat CD requires an understanding of mechanisms at the biochemical level. In this thesis, we attempted to gain a better understanding of certain pathways found to be active in Crohn’s disease-affected …

Rpe Vs. Percentage 1rm Loading In Periodized Programs Matched For Sets And Repetitions, Eric R. Helms, Ryan K. Byrnes, Daniel M. Cooke, Michael H. Haischer, Joseph P. Carzoli, Trevor K. Johnson, Matt R. Cross, John B. Cronin, Adam G. Storey, Michael C. Zourdos

Research outputs 2014 to 2021

Purpose: To investigate differences between rating of perceived exertion (RPE) and percentage one-repetition maximum (1RM) load assignment in resistance-trained males (19-35 years) performing protocols with matched sets and repetitions differentiated by load-assignment. Methods: Participants performed squats then bench press 3x/weeks in a daily undulating format over 8-weeks. Participants were counterbalanced by pre-test 1RM then assigned to percentage 1RM (1RMG, n = 11); load-assignment via percentage 1RMs, or RPE groups (RPEG, n = 10); participant-selected loads to reach target RPE ranges. Ultrasonography determined pre and post-test pectoralis (PMT), and vastus lateralis muscle thickness at 50 (VLMT50) and 70% (VLMT70) femur-length. Results: …

Inactivation Of Endoplasmic Reticulum Stress And The Prevention Of Neurodegenerative Diseases, Ian James Martins

Research outputs 2014 to 2021

Biotherapeutics and nutritional therapy are essential for the treatment of endoplasmic reticulum (ER) stress in diabetes and neurodegenerative diseases. Oxidative stress and nutrient excess may induce ER stress associated with activation of the unfolded protein response and connected to cell death. The heat shock gene Sirtuin 1 (Sirt 1) is important to the heat shock response with amyloid beta aggregation associated with the induction of mitophagy and ER stress in neuron cells. Genomic medicine that activates nuclear Sirt 1 is essential for the prevention of mitochondrial apoptosis and ER stress. Inhibitors such as drugs, alcohol, excess caffeine and palmitic acid …

Effect Of Metformin Exposure On Growth And Photosynthetic Performance In The Unicellular Freshwater Chlorophyte, Chlorella Vulgaris, Brittany M. Cummings, Joseph A. Needoba, Tawnya D. Peterson

OHSU-PSU School of Public Health Faculty Publications and Presentations

Many pharmaceuticals have negative effects on biota when released into the environment. For example, recent work has shown that the commonly prescribed antidiabetic drug, metformin (N,N-dimethylbiguanide), has endocrine disrupting effects on fish. However, effects of metformin on aquatic primary producers are poorly known. We exposed cultured isolates of a freshwater chlorophyte, Chlorella vulgaris, to a range of metformin concentrations (0– 767.9 mg L-1) to test the hypothesis that exposure negatively affects photosynthesis and growth. A cessation of growth, increase in non-photochemical quenching (NPQ, NPQmax), and reduced electron transport rate (ETR) were observed 24 h after exposure to a metformin concentration …

Pitx3null Mutant (Striatal Dopamine-Deficient) Mice Have Exaggerated Spiny Projection Neuron Responses To L-Dopa And D1 Agonism And Lack Baseline Striatonigral Spiking, Ben Sagot

Theses and Dissertations (ETD)

L-3,4 dihidroxyphenylalanine (l-DOPA) strongly stimulates motor activity in parkinsonian patients and animal models of Parkinson's disease. Severe striatal dopamine (DA) loss characterizes Parkinson's disease and its animal models. Given the canonical rate model of Parkinson's Disease pathophysiology based on differences in DA pharmacology manifesting as electrophysiological differences in striatal projection neuron (SPN) spike rates, SPNs should increase spiking during the motor response to l-DOPA. In fact, stimulating specific subsets of these neurons to spike in freely-moving wild type and parkinsonian animals causes or inhibits motor activity as predicted. However, pharmacological effects of DA deficiency, let alone those of DA replacement, …

Three-Dimensional Context Rather Than Nls Amino Acid Sequence Determines Importin Α Subtype Specificity For Rcc1., Rajeshwer S. Sankhala, Ravi K. Lokareddy, Salma Begum, Ruth A. Pumroy, Richard E. Gillilan, Gino Cingolani

Department of Biochemistry and Molecular Biology Faculty Papers

Active nuclear import of Ran exchange factor RCC1 is mediated by importin α3. This pathway is essential to generate a gradient of RanGTP on chromatin that directs nucleocytoplasmic transport, mitotic spindle assembly and nuclear envelope formation. Here we identify the mechanisms of importin α3 selectivity for RCC1. We find this isoform binds RCC1 with one order of magnitude higher affinity than the generic importin α1, although the two isoforms share an identical NLS-binding groove. Importin α3 uses its greater conformational flexibility to wedge the RCC1 β-propeller flanking the NLS against its lateral surface, preventing steric clashes with its Armadillo-core. Removing …

Synergy Of Two Low-Affinity Nlss Determines The High Avidity Of Influenza A Virus Nucleoprotein Np For Human Importin Α Isoforms., Wei Wu, Rajeshwer S. Sankhala, Tyler J Florio, Lixin Zhou, Nhan L.T. Nguyen, Ravi K. Lokareddy, Gino Cingolani, Nelly Panté

Department of Biochemistry and Molecular Biology Faculty Papers

The influenza A virus nucleoprotein (NP) is an essential multifunctional protein that encapsidates the viral genome and functions as an adapter between the virus and the host cell machinery. NPs from all strains of influenza A viruses contain two nuclear localization signals (NLSs): a well-studied monopartite NLS1 and a less-characterized NLS2, thought to be bipartite. Through site-directed mutagenesis and functional analysis, we found that NLS2 is also monopartite and is indispensable for viral infection. Atomic structures of importin α bound to two variants of NLS2 revealed NLS2 primarily binds the major-NLS binding site of importin α, unlike NLS1 that associates …

Compounds And Method Of Use As Anti-Infection Compounds And Therapeutic Agents To Regulate Cholesterol Metabolism, Joseph Chappell, Tom D. Niehaus, Kristin Brooke Linscott

Molecular and Cellular Biochemistry Faculty Patents

A compound is provided which comprises at least a portion of an amino acid linker-domain from squalene synthase. In alternative forms, the compound can include the amino-acid linker-domain from various fungus, including S. cerevisiae or the compound can be the functional equivalent and/or mimics an amino acid linker-domain from squalene synthase. A pharmaceutical composition includes the compound and may further include a pharmaceutical carrier. A method is provided for treating or controlling cholesterol metabolism and ergosterol metabolism in non-fungal organisms. One method includes a therapeutic treatment in humans by administering a therapeutically effective amount of the compound or pharmaceutical composition, …

A Mirna Signature For Cognitive Deficits And Alcohol Use Disorder In Persons Living With Hiv/Aids, Dorota Wyczechowska, Hui-Yi Lin, Andrea Laplante, Duane Jeansonne, Adam Lassak, Christopher H. Parsons, Patricia E. Molina, Francesca Peruzzi

School of Medicine Faculty Publications

HIV-associated neurocognitive disorders (HAND) affects more than half of persons living with HIV-1/AIDS (PLWHA). Identification of biomarkers representing the cognitive status of PLWHA is a critical step for implementation of successful cognitive, behavioral and pharmacological strategies to prevent onset and progression of HAND. However, the presence of co-morbidity factors in PLWHA, the most common being substance abuse, can prevent the identification of such biomarkers. We have optimized a protocol to profile plasma miRNAs using quantitative RT-qPCR and found a miRNA signature with very good discriminatory ability to distinguish PLWHA with cognitive impairment from those without cognitive impairment. Here, we have …

Mitochondrial Reactive Oxygen Species In Lipotoxic Hearts Induces Post-Translational Modifications Of Akap121, Drp1 And Opa1 That Promote Mitochondrial Fission, Kensuke Tsushima, Heiko Bugger, Adam R. Wende, Jamie Soto, Gregory A. Jenson, Austin R. Tor, Rose Mcglauflin, Helena C. Kenny, Yuan Zhang, Rhonda Souvenir, Xiao X. Hu, Crystal L. Sloan, Renata O. Pereira, Vitor A. Lira, Kenneth W. Spitzer, Terry L. Sharp, Kooresh I. Shoghi, Genevieve C. Sparagna, Eva A. Rog-Zielinska, Peter Kohl, Oleh Khalimonchuk, Jean E. Schaffer, E. Dale Abel

Department of Biochemistry: Faculty Publications

Rationale: Cardiac lipotoxicity, characterized by increased uptake, oxidation and accumulation of lipid intermediates, contributes to cardiac dysfunction in obesity and diabetes. However, mechanisms linking lipid overload and mitochondrial dysfunction are incompletely understood.

Objective: To elucidate the mechanisms for mitochondrial adaptations to lipid overload in postnatal hearts in vivo.

Methods and Results: Using a transgenic mouse model of cardiac lipotoxicity overexpressing long-chain acyl-CoA synthetase 1 in cardiomyocytes, we show that modestly increased myocardial fatty acid uptake leads to mitochondrial structural remodeling with significant reduction in minimum diameter. This is associated with increased palmitoyl-carnitine oxidation and increased reactive oxygen species (ROS) generation …

Xenobiotic-Induced Activation Of Human Aryl Hydrocarbon Receptor Target Genes In Drosophila Is Mediated By The Epigenetic Chromatin Modifiers, Angelina A. Akishina, J. E. Vorontsova, Roman O. Cherezov, Ilja B. Mertsalov, Olga G. Zatsepina, Mikhail S. Slezinger, Vladislav M. Panin, Svetlana Petruk, Grigori N. Enikolopov, Alexander M. Mazo, Olga B. Simonova, Boris A. Kuzin

Department of Biochemistry and Molecular Biology Faculty Papers

Aryl hydrocarbon receptor (AHR) is the key transcription factor that controls animal development and various adaptive processes. The AHR's target genes are involved in biodegradation of endogenous and exogenous toxins, regulation of immune response, organogenesis, and neurogenesis. Ligand binding is important for the activation of the AHR signaling pathway. Invertebrate AHR homologs are activated by endogenous ligands whereas vertebrate AHR can be activated by both endogenous and exogenous ligands (xenobiotics). Several studies using mammalian cultured cells have demonstrated that transcription of the AHR target genes can be activated by exogenous AHR ligands, but little is known about the effects of …

Difatty Acyl-Conjugated Linear And Cyclic Peptides For Sirna Delivery, Hung Do, Meenakshi Sharma, Naglaa Salem El-Sayed, Parvin Mahdipoor, Emira Bousoik, Keykavous Parang, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

A number of amphiphilic difatty acyl linear and cyclic R5K2 peptide conjugates were synthesized by solid-phase peptide methods to enhance the interaction with the hydrophobic cellular phospholipid bilayer and to improve siRNA delivery and silencing. Binding to siRNA molecules was significantly less for the cyclic peptide conjugates. A gradual decrease was observed in the particle size of the complexes with increasing peptide/siRNA ratio for most of the synthesized peptides, suggesting the complex formation. Most of the complexes showed a particle size of less than 200 nm, which is considered an appropriate size for in vitro siRNA delivery. A number of …