Biochemistry Commons^™

Comparative Screening Of Cytotoxic Potential Of Berberis Aristata And Senna Alexandrina Extracts, Rida Noor Akhtar, Javaria Zahoor, Rizwan Ullah Khan, Aziz Ullah, Naila Malkani

Journal of Bioresource Management

Medicinal plants provide a safe and efficient source of drugs for cancer treatment. Berberis aristata and Senna alexandrina are traditionally used to treat several ailments because they contain compounds with antimicrobial, antitoxic, anti-inflammatory, and other properties. The objective of the study was to prepare crude ethanolic extracts of B. aristata and S. alexandrina and to determine their cytotoxic potential against cancer cells. Ethanolic extracts were prepared for both plants. Hepatocellular carcinoma cells (HepG2) were used for all assays. The cytotoxicity of extracts was determined by 3‑(4,5‑Dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide (MTT) assay using various concentrations of extracts. The obtained sub-lethal concentrations were used …

In Vitro Anticancer Evaluation Of Tamoxifen And Paclitaxel-Loaded Chitosan Nanoparticles Against Breast And Lung Cancer With In Silico Docking, Arshia Amaan, Farah Mehak, Amer Jamil, Fatma Hussain

Journal of Bioresource Management

Breast and lung cancer are the primary cause of death worldwide, underlining the need for an improved therapeutic strategy. In the current study, tamoxifen (TAM) and paclitaxel (PTX) loaded chitosan nanoparticles (NPs) were produced for the evaluation of sustained drug delivery and enhanced anticancer potential of nanocarriers over conventional chemotherapy against breast and lung cancers, respectively. Nanoparticles were produced by the ionic gelation method and characterized by UV-visible spectroscopy, Dynamic Light Scattering and Fourier Transform Infrared Microscopy (FTIR), verifying the nanoscale morphology, stability and successful encapsulation. A drug release profile study (in vitro) (78 %, 60-75 %) and …

Investigating Quinclorac Binding To Human Serum Albumin Using Spectroscopy And Molecular Docking, Le Nguyen, L. Hicks, L. Jodoin, S. Carby, D. S. Sanford, D. Benavides, A. Mishra, R. Yadav

Journal of the Arkansas Academy of Science

Human serum albumin (HSA) is the most abundant plasma protein and serves as a major transporter and reservoir for a wide range of endogenous ligands, including fatty acids, heme, bilirubin, prostaglandins, and metal ions, as well as numerous exogenous compounds, such as pharmaceuticals. HSA is a 66 kDa monomeric, multidomain protein containing two principal ligand-binding sites, Sudlow sites I and II. Sudlow site I contains Trp214, the sole tryptophan residue in HSA, whose intrinsic fluorescence provides a sensitive probe for studying ligand–protein interactions.

In this study, the interaction between HSA and the persistent organochlorine herbicide quinclorac (QNC) was investigated using …

In Silico And Toxicological Evaluation Of Crescentia Cujete Aqueous Extract: Potential Anticancer Activity Against Breast Cancer, Rahma Diyan Martha, Fatimah Fatimah, Syahputra Wibowo, Bantari Wisynu Kusuma Wardhani, Josephine Elizabeth Siregar, Elisabeth Farah Novita Coutrier, Alfia Fitrianita, Andri Pramesyanti Pramono, Ita Margaretha Nainggolan, Yudhi Nugraha, Danar Danar, Naufal Abiyyu, Lalu Unsunnidhal, Aswin Rafif Khairullah, Arif Nur Muhammad Ansori, Hesty Parbuntari, Wimbuh Tri Widodo

Makara Journal of Science

Majapahit plant (Crescentia cujete), commonly found in Indonesia, has not been extensively explored for its medicinal properties. Given that many cancer treatments are derived from plants, this study aimed to examine the effects of plants on cancer chemical composition of the C. cujete fruit pulp extract, identify its primary compounds, and assess its potential as an antioxidant, anticancer agent, particularly for breast cancer. An insilico approach was used to evaluate the toxicity and interactions, of the compounds with cancer biomarker proteins, in addition to an in vivo Brine Shrimp Lethality Test (BSLT) for BSLT, toxicity screening using six …

Rna G-Quadruplexes Function As A Tunable Switch Of Fus Phase Separation, Jenny L. Carey, Miyuki Hayashi, Emily A. Welebob, Laura R. Ganser, Huan Wang, Kerry Buckhaults, Jacquelyn A. Depierro, Zheng Shi, James Shorter, Sua Myong, Aaron R. Haeusler, Lin Guo

Department of Biochemistry and Molecular Biology Faculty Papers

Fused in sarcoma (FUS) undergoes liquid-liquid phase separation (LLPS) to support essential cellular functions, but aberrant phase transitions promote toxic aggregation in neurodegenerative disease. Short RNA oligonucleotides can reverse this behavior, yet the structural determinants that govern RNA activity remain poorly defined. Here, we identify RNA G-quadruplexes (rG4s) as tunable structural motifs that potently modulate FUS LLPS. rG4 activity depends on its concentration and is modulated by rG4 length and stability: increasing repeat number switches rG4s from inhibitor to nucleator of FUS assembly, whereas chemical modifications that stabilize rG4 enhance inhibitory function and render these activities resilient to ionic perturbation. …

Histone Deacetylases In Kidney Injury: Distribution, Injury-Specific Regulation, And Fibroblast Hdac1 Function, Huy Nguyen

ETDs from 2020-2029

Acute kidney injury (AKI) is increasingly recognized as a major contributor to the development of chronic kidney disease (CKD) through maladaptive repair and interstitial fibrosis. Epigenetic regulation has emerged as a critical factor of kidney injury responses, however the injury-specific and cell-type specific roles of histone deacetylases (HDACs) remain poorly defined. This dissertation investigates the regulation and functional significance of HDACs in kidney injury, with a particular focus on fibroblast HDAC1 as a mediator of interstitial fibrosis development following AKI. In my cisplatin-induced AKI model, a single dose of cisplatin caused a significant decline in kidney function in both male …

Main-Chain Ion-Pair Polybenzimidazole Membranes Enabling Reduced-Temperature Ht-Pemfc Operation (Down To 120°C), Brian C. Benicewicz, Huina Lin

Faculty Publications

Proton exchange membrane (PEM) fuel cells are promising for clean and efficient energy conversion across diverse applications. High-temperature PEM fuel cells (HT-PEMFCs) using phosphoric acid (PA)-doped polybenzimidazole (PBI) can operate up to 200°C, but at lower temperatures, water-induced PA loss often leads to performance degradation and reduced durability. In this work, we present a new class of main-chain ion-pair PBI membranes by integrating the imidazolium-biphosphate ion-pair units directly into the PBI backbone. This design results in membranes with high acid content, stronger acid-polymer interactions and stabilized acid retention. In single-cell tests, the Im+-PBI15-3 wt.% exhibits peak power densities of 0.79 …

Elucidating The Mechanisms Of Complex Flavoprotein Dehydrogenases, Tyler Alt

Dissertations

Flavins are ubiquitous redox active cofactors that can catalyze electron transfer between substrates. They offer the advantage of being able to stabilize a range of oxidation and protonation states, as well being amenable to covalent modification, which can further alter their activity. As such, the scope of reactions catalyzed by flavoproteins is broad and flavin has implications in a range of biological processes. The two predominant forms of flavin that serve as redox active cofactors are flavin adenine mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are functionally homologous. A major complication of studying flavoprotein dehydrogenases, and one that has …

Allosteric And Uncompetitive Inhibition Of Yeast Alcohol Dehydrogenase Identified By Enzyme Kinetics, Dylan Jeremy Harrison, Jenny A. Cappuccio

IdeaFest: Interdisciplinary Journal of Creative Works and Research from Cal Poly Humboldt

Enzyme kinetics is a powerful technique used to quantify the rate at which an enzyme converts a substrate into a product and to identify potential inhibitors. In this study, kinetic analysis was employed to assess the activity of yeast alcohol dehydrogenase (YADH) in the presence and absence of sweeteners commonly found in alcoholic beverages. YADH catalyzes the oxidation of ethanol to acetaldehyde using NAD⁺ as a cofactor; the reduction to NADH can be monitored spectrophotometrically at 340 nm. Based on structural similarities to the ribose moiety of NAD⁺, it was hypothesized that sucrose and sucralose could directly interact with the …

Structure-Based Discovery Of Malate Dehydrogenase Inhibitors With Efficacy Against C. Parvum Oocysts, Ankita Bharatbhai Kheni

Biochemistry and Molecular Biology

Cryptosporidium parvum, the etiological agent of Cryptosporidiosis (diarrheal illness) represents a significant global health burden, particularly affecting immunodeficient and pediatric populations. Since the parasite has a highly reduced mitochondrion and relies on glycolysis, enzymes such as C. parvum malate dehydrogenase (CpMDH), which are believed to be indispensable for parasite viability due to their pivotal roles in NAD⁺ regeneration and redox balance, remain largely unexplored as therapeutic targets. The present study employed a multifaceted experimental and computational strategy to evaluate the inhibitory activity of two lead-like and drug-like small molecules, referred to as compound 1.8 and compound 1.5, against the cofactor …

Chromatin Insulators Homie And Nhomie Can Interact With Distant Copies Either Together Or Separately, With Distinct Outcomes For Enhancer-Promoter Interactions, Miki Fujioka, Wenfan Ke, Paul Schedl, James B. Jaynes

Department of Biochemistry and Molecular Biology Faculty Papers

Chromatin insulators, a.k.a. boundary elements, separate regions of the chromosome with distinct chromatin characteristics, including distinct histone modifications. This activity affects gene expression by allowing chromatin domains to be stably regulated and maintained. Insulators also block enhancer-promoter interactions and, somewhat paradoxically, facilitate other interactions, particularly when they stitch together distant regions of the chromosome by pairing with specific partners. Here we explore how long-range interactions facilitated by insulator pairing are affected by the presence of two potentially competing partners. Our results show that when two partners are present, they can reduce each other's effects on distant gene expression, suggesting that …

Synthesis And Characterization Of Organometallic Polymers And Their Cytotoxicity Towards Human Cancer Cell Lines, Paul Peter Slawek

Electronic Theses and Dissertations

This research aimed to synthesize organometallic polymers from dialkyl (methyl, ethyl, butyl, cyclohexyl, and octyl) and diaryl (phenyl) tin dichlorides and three organic monomers, dipicolinic acid (DPA), chloramphenicol (CH), and isomannide (IS), using interfacial polymerization. Structure-activity relationships were investigated through physicochemical characterization (light-scattering photometry, proton NMR, and IR spectroscopy) and cytotoxicity was evaluated against six human cancer cell lines (AsPC-1, PANC-1, MCF-7, MDA-MB-231, HT-29, PC-3), with cisplatin serving as the reference standard.

Five DPA/tin polymers were synthesized, with IC₅₀ values in the range of 0.60–0.71 μg/mL. Their cytotoxicity was significantly lower than that of cisplatin (0.0023-0.044 μg/mL), suggesting that …

Synthesis And Characterization Of Synergistic Bioactive– Organometallic Condensation Polymers, Francesca Isabel Mosca

Electronic Theses and Dissertations

This research focuses on the synthesis and structural characterization of polymers with anticipated anticancer and antiviral properties by combining metal-containing Lewis acids, organotin dichlorides (R2SnCl2), Group 4 metallocene dichlorides (Cp2TiCl2, Cp2ZrCl2 and Cp2HfCl2), and triphenyl Group 15 metal dichlorides (Ph3AsCl2, Ph3SbCl2 and Ph3BiCl2), with biologically active Lewis bases, lamivudine, a synthetic nucleoside, and camphoric acid, a dicarboxylic acid, to achieve synergistic effect.

Five classes of polymers were synthesized using interfacial polymerization: lamivudine and organotin dichlorides, lamivudine and Group 4 metallocene dichlorides, camphoric acid and triphenyl Group 15 metal dichlorides, camphoric acid and organotin dichlorides, and camphoric acid and Group 4 …

Napier Grass (Pennisetum Purpureum) Meal Modulates Growth Efficiency, Gut Morphology, And Systemic Health In Broiler Chickens, Eric Lim Teik Chung, Yee Lyn Ong, Nazri Nayan, Muhamad Faris Ab Aziz, Faez Firdaus Abdullah Jesse, Faizal Andri, Arissara Sopawong

The Thai Journal of Veterinary Medicine

Grass and leaf meals, which include vital phytocompounds, have the potential to be a natural and safe alternative to antibiotics in the poultry industry. Therefore, this study aims to assess Pennisetum purpureum leaf meal and its phytocompounds on the health performances of colored-broilers. A total of 216 unsexed Sasso chicks were assigned to six diet groups. The negative control (T1) received a commercial basal diet without antibiotics, while the positive control (T2) received the same diet with oxytetracycline (100 mg/kg). Groups T3 to T6 received no antibiotics and included P. purpureum meal at 1.25, 2.50, 3.75, or 5.00 grams per …

Hydroxamate Formation In The Lipopeptide Containing Siderophore Taiwachelin, Aaron J. Gringer, Kernen P. Agwaza, Isabel Da Fonseca, Pablo Sobrado

Chemistry Faculty Research & Creative Works

Cupriavidus taiwanensis is a nitrogen-fixing bacterium found in root nodules of the invasive tropical weed Mimosa pudica . C. taiwanensis has been shown to grow in environments contaminated with heavy metals such as Pb, Cu, and Cd. Taiwachelin, a recently identified siderophore produced by C. taiwanensis , is an iron chelator that contains a hydroxamate functional group for metal binding. In its biosynthesis, a flavin-dependent N-monooxygenase (NMO) was predicted to hydroxylate l -ornithine, leading to formation of the metal binding hydroxamate moiety. Here, we report the cloning, expression, and biochemical characterization of this enzyme, herein referred to as CtNMO. CtNMO …

Immunomodulatory And Signaling Molecules From Plant-Associated Bacteria: Toll-Like Receptor 4 Agonist Adjuvants And Diketopiperazine-Mediated Communication, Marian Romaine

Dissertations, Theses, and Capstone Projects

Medicinal plants and their associated microbiomes constitute a rich source of bioactive natural products with applications in immunotherapy and microbial ecology. Herbal formulations have long been valued for safe immune enhancement, while bacterial signaling molecules govern community behaviors critical to pathogenesis, symbiosis, and environmental processes. Bacterial lipopolysaccharides (LPS) from plant-associated Gram-negative bacteria have emerged as potent TLR4 agonists, yet their endotoxic potential limits direct use, and diketopiperazines (DKPs) serve as versatile quorum-sensing mediators capable of modulating biofilms in mixed microbial systems.

The work in this thesis comprises two independent but complementary research strands. The first strand pursued the engineering of …

Identifying Textual Predictors Of Early Termination In Clinical Trials In Medicine: An Explainable Machine-Learning Study, Rohan Ramnarain

Dissertations, Theses, and Capstone Projects

About one in five clinical trials in medicine ends early, wasting valuable resources and reducing the evidence available for developing life-saving medical treatments. This project uses a method called Trial2Vec, which is a self-supervised machine-learning method that converts clinical trial documents into dense numerical representations that capture their key design and clinical characteristics, to turn each proposed clinical trial’s written protocol into a compact numerical profile (a process referred to as embedding). These profiles are then paired with a predictive machine learning models to identify the words and phrases in the trial documents that can signal a higher risk of …

Structure Of Ergosteryl-Aspartate Synthase Reveals How An Entrapped Trna Is Used Like A Prosthetic Swinging Arm In The Synthesis Of Aminoacylated Sterols, Hanako Murayama, Nathaniel Yakobov, Nassira Mahmoudi, Sasha Legrosdidier, Nicolas Fournier, Solène Zuttion, Kanata Matsumoto, Michihiro Nishimura, Jingwei Ji, Bruno Senger, Laurence Huck, Howard Gamper, Yoshiaki Kise, Ralph Kleiner, Mathieu Frechin, Ya-Ming Hou, Hubert Becker, Yuzuru Itoh, Frédéric Fischer, Osamu Nureki

Department of Biochemistry and Molecular Biology Faculty Papers

Ergosteryl-3β-O-L-aspartate synthase (ErdS) catalyzes tRNA-dependent aspartylation of ergosterol, a lipid essential for fungal cell membrane integrity. However, the functional significance of ergosteryl-aspartate and the molecular mechanisms underlying its synthesis remain unclear. Here, we show that ErdS localization is highly dynamic and that Erg-Asp is required for proper hyphal growth, sporulation, and spore germination, and likely influences stress tolerance. The cryo-electron microscopy structure of ErdS revealed an unprecedented sterol-binding pocket. In addition, the structures in complex with a non-hydrolyzable Asp-N-tRNAAsp show a tRNA-guided intramolecular aminoacyl transfer mechanism between two functional domains of the enzyme. The CCA end of tRNAAsp undergoes a …

High-Throughput Robotic Ethanol Inhibition Assays For Engineered Thermophilic Biofuel Strains, Kevin He, Daniel Olson, Marybeth Maloney, Anthony Lanahan

Wetterhahn Science Symposium Posters

Ethanol stress assays are commonly used to evaluate microbial tolerance, metabolic adaptation, and fermentation performance. However, manual liquid handling introduces variability across replicate wells and small-volume pipetting steps, limiting reproducibility and throughput. This study developed an automated OT-2 robotic workflow to generate replicated ethanol concentration gradients for high-throughput inhibition assays in engineered thermophilic biofuel strains. Kinetic plate-reader measurements were used to quantify ethanol-dependent growth responses under anaerobic fermentation conditions. The reasearch question is: How do engineered thermophilic biofuel strains differ in ethanol-dependent growth inhibition under anaerobic fermentation conditions, and can automated robotic assays improve the reproducibility of these measurements? Can …

Crystal Structure Of Mouse Dxo In Complex With The Udp-N-Acetylglucosamine Cap And Molecular Mechanism For The Decapping Reactions, Najeeb Ullah, Selom K. Doamekpor, Liang Tong

Department of Biochemistry and Molecular Biology Faculty Papers

Noncanonical metabolite 5' caps have recently been identified on RNAs, and the DXO/Rai1 family of enzymes can remove these caps in eukaryotes. While the binding modes of NAD, FAD and dephospho-CoA (dpCoA) caps in the active site of mouse DXO have been determined, how DXO recognizes the UDP-glucose (UDP-Glc) and UDP-N-acetylglucosamine (UDP-GlcNAc) caps is not known. In addition, the molecular mechanism by which DXO catalyzes the decapping reactions is still poorly understood, especially the location of the water/hydroxide that attacks the scissile phosphate to initiate the decapping. Here we report the crystal structure of mouse DXO in complex with UDP-GlcNAc …