Molecular Mechanism Behind The Safe Immunostimulatory Effect Of Withania Somnifera,
2023
CUNY Graduate Center
Molecular Mechanism Behind The Safe Immunostimulatory Effect Of Withania Somnifera, Kriti Kalpana, Shen Yap, Moriya Tsuji, Akira Kawamura
Publications and Research
Withania somnifera (L.) Dunal (family Solanaceae) is a medicinal plant known for, among many pharmacological properties, an immune boosting effect. Our recent study revealed that its key immunostimulatory factor is lipopolysaccharide of plant-associated bacteria. This is peculiar, because, although LPS can elicit protective immunity, it is an extremely potent pro-inflammatory toxin (endotoxin). However, W. somnifera is not associated with such toxicity. In fact, despite the presence of LPS, it does not trigger massive inflammatory responses in macrophages. To gain insights into the safe immunostimulatory effect of W. somnifera, we conducted a mechanistic study on its major phytochemical constituent, …
Structure–Activity Relationship Studies On 6-Chloro-1-Phenylbenzazepines Leads To The Identification Of A New Dopamine D1 Receptor Antagonist,
2023
CUNY Hunter College
Structure–Activity Relationship Studies On 6-Chloro-1-Phenylbenzazepines Leads To The Identification Of A New Dopamine D1 Receptor Antagonist, Rajan Giri, Hari K. Namballa, Vishwashiv Emogaje, Wayne W. Harding
Publications and Research
The 1-phenylbenzazepine template has yielded a number of D1R-like ligands, which, though useful as pharmacological tools, have significant drawbacks in terms of selectivity versus D5R as well as pharmacokinetic behavior. A number of 1-phenylbenzazepines contain a 6-chloro functional group, but extensive SAR studies around the 6-chloro-1-phenylbenzazepine framework have not been reported in the literature. To further understand the tolerance of the 6-chloro-1-phenylbenzazepine template for various substituent groups towards affinity and selectivity at D1R, we synthesized two series of analogs with structural variations at the C-7, C-8, N-3, C-3′ and C-4′ positions. The series 2 analogs differed from …
Tcga Expression Analyses Of 10 Carcinoma Types Reveal Clinically Significant Racial Differences,
2023
CUNY Brooklyn College
Tcga Expression Analyses Of 10 Carcinoma Types Reveal Clinically Significant Racial Differences, Brian Lei, Xinyin Jiang, Anjana Saxena
Publications and Research
Epidemiological studies reveal disparities in cancer incidence and outcome rates between racial groups in the United States. In our study, we investigated molecular differences between racial groups in 10 carcinoma types. We used publicly available data from The Cancer Genome Atlas to identify patterns of differential gene expression in tumor samples obtained from 4112 White, Black/African American, and Asian patients. We identified race-dependent expression of numerous genes whose mRNA transcript levels were significantly correlated with patients’ survival. Only a small subset of these genes was differentially expressed in multiple carcinomas, including genes involved in cell cycle progression such as CCNB1 …
Lead Induced Differences In Bone Properties In Osteocalcin +/+ And −/− Female Mice,
2023
CUNY Brooklyn College
Lead Induced Differences In Bone Properties In Osteocalcin +/+ And −/− Female Mice, G. Yildirim, W. C. Budell, O. Berezovska, S. Yagerman, S. S. Maliath, P. Mastrokostas, S. Tommasini, T. L. Dowd
Publications and Research
Lead (Pb) toxicity is a major health problem and bone is the major reservoir. Lead is detrimental to bone, affects bone remodelingand is associated with elderly fractures. Osteocalcin (OC) affects bone remodeling, improves fracture resistance and decreases with age and in some diseases. The effect of lead in osteocalcin depleted bone is unknown and of interest. We compared bone mineral properties of control and Pb exposed (from 2 to 6 months) femora from female adult C57BL6 OC+/+ and OC−/− mice using Fourier Transform Infrared Imaging (FTIRI), Micro-computed tomography (uCT), bone biomechanical measurements and serum turnover markers (P1NP, CTX). Lead significantly …
Development Of Multivalent Dna-Peptide Nucleosome Mimetics And Multi-Domain Protein Inhibitors That Directly Or Indirectly Target The E3 Ligase Uhrf1,
2023
University of the Pacific
Development Of Multivalent Dna-Peptide Nucleosome Mimetics And Multi-Domain Protein Inhibitors That Directly Or Indirectly Target The E3 Ligase Uhrf1, Li Gu
University of the Pacific Theses and Dissertations
UHRF1 is an E3 ubiquitin ligase and a key epigenetic regulator establishing a crosstalk between DNA methylation and histone modification. Despite the important biochemical role of UHRF1 in cells, its overexpression has been found in almost all primary cancer types including breast cancer, lung cancer and so on. Numerous evidence indicates a strong link between tumorigenesis and UHRF1 overexpression, supporting its potential as a universal biomarker for cancer. However, UHRF1 is “yet-to-be drugged” and no highly potent chemical probes have been developed to target UHRF1 to date. In this study, we proposed two drug design approaches for UHRF1. The first …
Interactions Of Amyloid Peptides With Lipid Membranes,
2022
New Jersey Institute of Technology
Interactions Of Amyloid Peptides With Lipid Membranes, Yanxing Yang
Dissertations
The aggregation of amyloid proteins into fibrils is a hallmark of several diseases including Alzheimer’s (AD), Parkinson’s, and Type II diabetes. This aggregation process involves the formation of small size oligomers preceding the formation of insoluble fibrils. Recent studies have shown that these oligomers are more likely to be responsible for cell toxicity than fibrils. A possible mechanism of toxicity involves the interaction of oligomers with the cell membrane compromising its integrity. In particular, oligomers may form pore-like structures in the cell membrane affecting its permeability or they may induce lipid loss via a detergent-like effect. This dissertation aims to …
Angiogenic Supports For Microvascular Engineering,
2022
New Jersey Institute of Technology
Angiogenic Supports For Microvascular Engineering, Zain Siddiqui
Dissertations
Ischemic tissue disease is caused by a lack of circulation / blood supply to tissue. This can be treated by introducing a number of angiogenic (pro-blood vessel forming) factors into the tissue. This work presents strategies for ischemic tissue treatment utilizing a novel proangiogenic self-assembling peptide hydrogel platform. To demonstrate the utility of this platform, its use alone as an angiogenic therapeutic (both alone as a self-assembling hydrogel and with two-component systems), and its ability to vascularize implants is explored. Due to these angiogenic scaffolds demonstrating efficacy to regenerate microvasculature, this work evaluates diseases that can be treated by the …
Production Of Biofuel Using Magnetic Nanocatalyst Zno-Ni0.5zn0.5fe2o4-Fe2o3: A Mini-Review Of Recent Studies,
2022
Department of Chemistry, University of Poonch Rawalaakot, Rawalaakot, AJK, Pakistan
Production Of Biofuel Using Magnetic Nanocatalyst Zno-Ni0.5zn0.5fe2o4-Fe2o3: A Mini-Review Of Recent Studies, Nida Ziafat Miss, Majid Mahmood
Journal of Bioresource Management
As conventional fossil fuels are becoming limited, it is critical to find alternative clean and renewable energy sources. Biodiesel is a degradable and renewable form of fuel made up of long-chain fatty acid esters that can be generated from either plants or animals. It is a mixture of long-chain alkyl esters made through a transesterification reaction with alcohol and catalyst. Due to the high cost of petroleum, the concept of biofuel production as an alternative source has increased in recent years. The present mini-review summarizes some recent studies on alternative methods for the production of biofuel. The review concludes that …
Phytochemical Constituents, Haematological Activities And Gc-Ms Analysis Of Isolated Oil Of Rosary Pea (Abrus Precatorius) In Wistar Rat Fed With High Lipid Diet,
2022
Department of Chemistry, Faculty of Physical Sciences, University of Benin, P.M.B. 1154, Benin City, Nigeria.
Phytochemical Constituents, Haematological Activities And Gc-Ms Analysis Of Isolated Oil Of Rosary Pea (Abrus Precatorius) In Wistar Rat Fed With High Lipid Diet, Osaro Iyekowa, Opara V Ndubuisi
Tanzania Journal of Science
The study is aimed at investigating the phytochemical constituents and haematological activities of the isolated oil in Wistar rat fed with high lipid diet. Powdered leaves of Abrus precatorious were extracted and phytochemical screening was done according to prescribed standard methods, while vacuum liquid chromatography (VLC) was adopted for oil isolation of the crude extract and characterized by gas chromatography-mass spectrometry (GC-MS). Thirty adult Wistar rats were randomly arranged into six groups (A, B, C, D, E and F) and treated under certain conditions. Haematological analyses were performed according to standard procedures. Saponins, alkaloids, terpenoids, flavonoids and glycosides were present. …
Determination Of Sugars, Amino Acids, Ph And Alcohol In Bamboo Beverage From Southern Highlands, Tanzania,
2022
Department of Food Science and Technology, University of Dar es Salaam, Dar es Salaam, Tanzania
Determination Of Sugars, Amino Acids, Ph And Alcohol In Bamboo Beverage From Southern Highlands, Tanzania, Lilian D Kaale
Tanzania Journal of Science
The amounts of sugars and amino acids play significant roles in defining the fermentation process and quantifying the alcohol levels in beverages, while pH affects the biological stability, colour, oxidation rate, and protein stability of alcoholic beverages. This study investigated the sugar content, amino acids, alcohol levels, and pH of bamboo beverage from Tanzania's southern highlands. During storage, the sugars significantly decreased (p < 0.05), especially when kept at room temperature from 52.96 to 0.00 (source 1), 53.35 to 0.00 (source 2) and 53.57 to 0.00 (source 3) g/L for fructose, from 47.93 to 14.78 (source 1), 47.23 to 14.91 (source 2) and 47.61 to 14.77 (source 3) g/L for glucose, and from 0.40 to 0.00 (source 1), 0.36 to 0.00 (source 2) and 0.37 to 0.00 (source 3) g/L for sucrose after six days of storage. A total of 15 amino acids were determined from the bamboo beverage with tyrosine being the most prevalent (597.68 mg/L for source 1, 599.44 mg/L for source 2 and 597.83 mg/L for source 3), followed by valine (261.13 mg/L for source 1, 261.24 mg/L for source 2 and 262.54 mg/L for source 3), threonine (76.69 mg/L for source 1, 76.91 mg/L for source 2 and 77.13 mg/L for source 3), and serine (66.37 mg/L for source 1, 67.23 mg/L for source 2 and 66.68 mg/L for source 3). After six days of storage at room temperature, there was a significant decrease in pH from 4.04 to 3.63. Alcohol content ranged from 3.11 to 9.05% v/v at the room temperature storage. These results might facilitate the optimal use of bamboo beverages, which have been neglected due to lack of scientific information such as amino acid and sugar levels. Keywords: Bamboo beverage, ulanzi, amino acids, sugars, alcohol content.
Hiv-Tat Exacerbates The Actions Of Atazanavir, Efavirenz, And
Ritonavir On Cardiac Ryanodine Receptor (Ryr2),
2022
Imam Abdulrahman Bin Faisal University
Hiv-Tat Exacerbates The Actions Of Atazanavir, Efavirenz, And Ritonavir On Cardiac Ryanodine Receptor (Ryr2), Imam Abdulrahman Bin Faisal University, Chengju Tian, Sean R. Bidasee, Zachary L. Venn, Evan Schroder, Nick Y. Palermo, Mohammad Alshabeeb, Benson J. Edagwa, Jason J. Payne, Keshoer R. Bidasee
Department of Biochemistry: Faculty Publications
The incidence of sudden cardiac death (SCD) in people living with HIV infection (PLWH), especially those with inadequate viral suppression, is high and the reasons for this remain incompletely characterized. The timely opening and closing of type 2 ryanodine receptor (RyR2) is critical for ensuring rhythmic cardiac contraction–relaxation cycles, and the disruption of these processes can elicit Ca2+ waves, ventricular arrhythmias, and SCD. Herein, we show that the HIV protein Tat (HIVTat: 0–52 ng/mL) and therapeutic levels of the antiretroviral drugs atazanavir (ATV: 0–25,344 ng/mL), efavirenz (EFV: 0–11,376 ng/mL), and ritonavir (RTV: 0–25,956 ng/mL) bind to and modulate the …
Therapies For Mitochondrial Disorders,
2022
Technological University of the Shannon: Midlands Midwest
Therapies For Mitochondrial Disorders, Kayli Sousa Smyth, Anne Mulvihill
SURE Journal: Science Undergraduate Research Experience Journal
Mitochondria are cytoplasmic, double-membrane organelles that synthesise adenosine triphosphate (ATP). Mitochondria contain their own genome, mitochondrial DNA (mtDNA), which is maternally inherited from the oocyte. Mitochondrial proteins are encoded by either nuclear DNA (nDNA) or mtDNA, and both code for proteins forming the mitochondrial oxidative phosphorylation (OXPHOS) complexes of the respiratory chain. These complexes form a chain that allows the passage of electrons down the electron transport chain (ETC) through a proton motive force, creating ATP from adenosine diphosphate (ADP). This study aims to explore current and prospective therapies for mitochondrial disorders (MTDS). MTDS are clinical syndromes coupled with abnormalities …
Machine Learning And Protein Allostery,
2022
Southern Methodist University
Machine Learning And Protein Allostery, Sian Xiao, Gennady M. Verkhivker, Peng Tao
Mathematics, Physics, and Computer Science Faculty Articles and Research
The fundamental biological importance and complexity of allosterically regulated proteins stem from their central role in signal transduction and cellular processes. Recently, machine-learning approaches have been developed and actively deployed to facilitate theoretical and experimental studies of protein dynamics and allosteric mechanisms. In this review, we survey recent developments in applications of machine-learning methods for studies of allosteric mechanisms, prediction of allosteric effects and allostery-related physicochemical properties, and allosteric protein engineering. We also review the applications of machine-learning strategies for characterization of allosteric mechanisms and drug design targeting SARS-CoV-2. Continuous development and task-specific adaptation of machine-learning methods for protein allosteric …
Compatibility Of Crude Oil Blends─Processing Issues Related To Asphaltene Precipitation, Methods Of Instability Prediction─A Review,
2022
Kettering University
Compatibility Of Crude Oil Blends─Processing Issues Related To Asphaltene Precipitation, Methods Of Instability Prediction─A Review, Krzysztof Bambinek, Andrzej Przyjazny, Grzegorz Boczkaj
Natural Sciences Publications
Processing crude oil of variable composition, especially due to the need to process crude oil blends obtained from various sources, presents a tremendous process challenge. This is mainly due to the destabilization of the colloidal system manifested mostly by the precipitation of the asphaltene fraction. The precipitation of asphaltenes from crude oil is a serious problem during extraction, transport, and processing. In the latter case, engineers and scientists have spent a lot of time determining what mechanisms are conducive to the occurrence of this phenomenon. On the one hand, there was a scientific curiosity about the principles of the nanoworld …
Arginine Methylation Of The Pgc-1Α C‑Terminus Is Temperature- Dependent,
2022
California State University, Los Angeles
Arginine Methylation Of The Pgc-1Α C‑Terminus Is Temperature- Dependent, Meryl Mendoz, Mariel Mendoza, Tiffany Lubrino, Sidney Briski, Immaculeta Osuji, Janielle Cuala, Brendan Ly, Ivan Ocegueda, Harvey Peralta, Benjamin A. Garcia, Cecilia Zurita-Lopez
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
We set out to determine whether the C-terminus (amino acids 481–798) of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α, UniProt Q9UBK2), a regulatory metabolic protein involved in mitochondrial biogenesis, and respiration, is an arginine methyltransferase substrate. Arginine methylation by protein arginine methyltransferases (PRMTs) alters protein function and thus contributes to various cellular processes. In addition to confirming methylation of the C-terminus by PRMT1 as described in the literature, we have identified methylation by another member of the PRMT family, PRMT7. We performed in vitro methylation reactions using recombinant mammalian PRMT7 and PRMT1 at 37, 30, 21, 18, and 4 °C. …
Quantum Computations And Molecular Dynamics Simulations: From The Fundamentals Of Antimicrobial Resistance To Neurological Diseases,
2022
Duquesne University
Quantum Computations And Molecular Dynamics Simulations: From The Fundamentals Of Antimicrobial Resistance To Neurological Diseases, Angel Tamez
Electronic Theses and Dissertations
Biophysical phenomena are modeled using a combination of quantum and classical methods to interpret and supplement three distinct and diverse problems in this dissertation. In the first project, decarboxylation reactions are ubiquitous across chemical and biological disciplines, yet the origin of non-catalytic solvent effects remains elusive. Specific solvent structure and energetics have not been well described for the monoanion of malonate, nor corrected from the gas-phase charge-assisted intramolecular hydrogen bond model known as “pseudochair”. In the aqueous phase, a low-lying energy conformer known as the “orthogonal conformation” is computed to be preferred by a three-water cluster of hydrogen bonding over …
Characterization Of Ape1 And Dna G-Quadruplex Interaction In Transcription Regulation And Dna Damage Repair,
2022
University of Nebraska Medical Center
Characterization Of Ape1 And Dna G-Quadruplex Interaction In Transcription Regulation And Dna Damage Repair, Suravi Pramanik
Theses & Dissertations
Human AP Endonuclease 1 (APE1) is the primary enzyme in the base excision repair (BER) pathway that repairs apurinic/apyrimidinic (AP) sites, the most frequently formed DNA lesions in the genome. Recently, through genome-wide mapping analysis, we have shown that APE1, as well as its post-translationally modified form, acetylated APE1 (AcAPE1), is enriched in the gene regulatory regions. The APE1/AcAPE1-enriched regions also harbor Guanine (G)-rich sequences that fold into DNA secondary structures called G-quadruplexes (G4s). Our lab has demonstrated a strong genome-wide correlation between the occurrence of G4 structures and the binding of APE1 and AcAPE1. However, it is unknown whether …
Metoprolol Disrupts Sterol Biosynthesis Through Inhibition Of 7-Dehydrocholesterol Reductase (Dhcr7),
2022
University of Nebraska Medical Center
Metoprolol Disrupts Sterol Biosynthesis Through Inhibition Of 7-Dehydrocholesterol Reductase (Dhcr7), Luke B. Allen
Theses & Dissertations
Cholesterol is essential for life. It is particularly important in the brain as it relies on de novo synthesis of cholesterol following the formation of the blood brain barrier (BBB). As such, disrupting sterol biosynthesis during neurodevelopment can have devastating outcomes. The most common post-lanosterol sterol biosynthesis disorder, Smith-Lemli-Opitz Syndrome, arises from a faulty DHCR7 enzyme. DHCR7 has also been shown to be inhibited by several psychotropic medications. Here we assess six beta-blockers and their effects on sterol biosynthesis in vitro. Two beta-blockers, metoprolol and nebivolol strongly inhibit DHCR7 in four separate in vitro models of both mouse and …
The Role Of Parkin In Mitochondrial Dna,
2022
University of Nebraska Medical Center
The Role Of Parkin In Mitochondrial Dna, Eliezer Lichter
Theses & Dissertations
Mitochondria are at the center of biological phenomena such as aging and diseases, especially neurodegenerative diseases. While the discovery of mitochondria only came approximately 200 years after the cell was discovered, a lot of progress has been made since. The mitochondrial genome encodes proteins vital for mitochondrial function. These proteins are only a subset of the proteins present in mitochondria; the rest are nuclear encoded. The nucleus also encodes cytosolic proteins vital for mitochondrial maintenance. One of these is Parkin, an E3 ubiquitin ligase that ubiquitinates mitochondrial proteins as mitochondria become depolarized. Its activity has been shown to be involved …
Structural And Biochemical Studies Of Three Enzymes Involved In Amino Acid Metabolism To Develop Novel Drugs,
2022
University of Nebraska Medical Center
Structural And Biochemical Studies Of Three Enzymes Involved In Amino Acid Metabolism To Develop Novel Drugs, Yahani Pankaja Jayasinghe Arachchige
Theses & Dissertations
Intrinsic drug resistance in bacteria predates the clinical use of antibiotics. Additionally, heterogeneous metabolic states and the ability of many bacteria to form biofilms further enhances bacterial survival during infection and exacerbates treatment challenges. This necessitates the identification of novel drugs against new drug targets. These studies focus on the development of compounds targeting enzymes in Mycobacterium tuberculosis (Mtb) and Staphylococcus aureus that avoid intrinsic antibiotic defenses. The Mtb-encoded homoserine transacetylase enzyme (HTA) catalyzes the first step of the methionine biosynthesis pathway that produces methionine and S-adenosyl methionine. These compounds are shown to be essential for both dormant …
