Biochemistry, Biophysics, and Structural Biology Commons^™

Structural And Spectroscopic Study Of New Copper(Ii) And Zinc(Ii) Complexes Of Coumarin Oxyacetate Ligands And Determination Of Their Antimicrobial Activity, Muhammad Mujahid, Natasha Trendafilova, Georgina Rosair, Kevin Kavanagh, Maureen Walsh, Bernadette Creaven, Ivelina Georgieva

Articles

Tackling antimicrobial resistance is of increasing concern in a post-pandemic world where overuse of antibiotics has increased the threat of another pandemic caused by antimicrobial-resistant pathogens. Derivatives of coumarins, a naturally occurring bioactive compound, and its metal complexes have proven therapeutic potential as antimicrobial agents and in this study a series of copper(II) and zinc(II) complexes of coumarin oxyacetate ligands were synthesised and characterised by spectroscopic techniques (IR, 1H, 13C NMR, UV-Vis) and by X-ray crystallography for two of the zinc complexes. The experimental spectroscopic data were then interpreted on the basis of molecular structure modelling and subsequent spectra simulation …

Review Of The Valorization Initiatives Of Brewing And Distilling Byproducts, Ekene C. Umego, Catherine Barry-Ryan

Articles

Beer and spirits are two of the most consumed alcoholic beverages in the world, and their production generates enormous amounts of by-product materials. This ranges from spent grain, spent yeast, spent kieselguhr, trub, carbon dioxide, pot ale, and distilled gin spent botanicals. The present circular economy dynamics and increased awareness on resource use for enhanced sustainable production practices have driven changes and innovations in the management practices and utilisation of these by-products. These include food product development, functional food applications, biotechnological applications, and bioactive compounds extraction. As a result, the brewing and distilling sector of the food and drinks industry …

Contributions Of Vibrational Spectroscopy To Virology: A Review, Iqra Chaudhary, Naomi Jackson, Denise Denning, Luke O'Neill, Hugh Byrne

Articles

Vibrational spectroscopic techniques, both infrared absorption and Raman scattering, are high precision, label free analytical techniques which have found applications in fields as diverse as analytical chemistry, pharmacology, forensics and archeometrics and, in recent times, have attracted increasing attention for biomedical applications. As analytical techniques, they have been applied to the characterisation of viruses as early as the 1970s, and, in the context of the coronavirus disease 2019 (COVID-19) pandemic, have been explored in response to the World Health Organisation as novel methodologies to aid in the global efforts to implement and improve rapid screening of viral infection. This review …

G Protein–Coupled Receptor 21 In Macrophages: An In Vitro Study, Valentina Bordano, Gemma K. Kinsella, Stefania Cannito, Chiara Dianzani, Casimiro Luca Gigliotti, John C. Stephens, Chiara Monge, Claudia Bocca, Arianna C. Rosa, Gianluca Miglio, Umberto Dianzani, John B.C. Findlay, Elisa Benetti

Articles

GPR21 is an orphan and constitutively active receptor belonging to the superfamily of G-Protein Coupled Receptors (GPCRs). GPR21 couples to the Gq family of G proteins and is markedly expressed in macrophages. Studies of GPR21 knock-out mice indicated that GPR21 may be involved in promoting macrophage migration. The aim of this study was to evaluate the role of GPR21 in human macrophages, analyzing (i) its involvement in cell migration and cytokine release and (ii) the consequence of its pharmacological inhibition by using the inverse agonist GRA2. THP-1 cells were activated and differentiated into either M1 or …

Combining Pharmacokinetics And Vibrational Spectroscopy: Mcr-Als Hard-And-Soft Modelling Of Drug Uptake In Vitro Using Tailored Kinetic Constraints, David Perez-Guaita, Guillermo Quintas, Zeineb Farhane, Roma Tauler, Hugh Byrne

Articles

Raman microspectroscopy is a label-free technique which is very suited for the investigation of pharmacokinetics of cellular uptake, mechanisms of interaction, and efficacies of drugs in vitro. However, the complexity of the spectra makes the identification of spectral patterns associated with the drug and subsequent cellular responses difficult. Indeed, multivariate methods that relate spectral features to the inoculation time do not normally take into account the kinetics involved, and important theoretical information which could assist in the elucidation of the relevant spectral signatures is excluded. Here, we propose the integration of kinetic equations in the modelling of drug uptake and …

In Vitro Toxicological Evaluation Of Mesoporous Silica Microparticles Functionalised 1 With Carvacrol And Thymol, Cristina Fuentes, Ana Fuentes, Hugh Byrne, José Barat, María José Ruiz

Articles

The cytotoxicity of carvacrol- and thymol- functionalised mesoporous silica microparticles (MCM-41) was assessed in the human hepatocarcinoma cell line (HepG2). Cell viability, lactate dehydrogenase (LDH) activity, reactive oxygen species (ROS) production, mitochondrial membrane potential (ΔΨm), lipid peroxidation (LPO) and apoptosis/necrosis analysis were used as endpoints. Results showed that both materials induced cytotoxicity in a time and concentration-dependent manner, being more cytotoxic than free essential oil components and bare MCM-41. This effect was caused by the cell-particle interactions and not from degradation products released to the culture media, as demonstrated in the extract dilution assays. LDH release was seen to be …

Extracellular Secretion Of A Cutinase With Polyester-Degrading Potential By E. Coli Using A Novel Signal Peptide From Amycolatopsis Mediterranei, Yeqi Tan, Gemma K. Kinsella, Gary T. Henehan, Barry J. Ryan

Articles

Recent studies in this laboratory showed that an extracellular cutinase from A. mediterranei (AmCut) was able to degrade the plastics polycaprolactone and polybutylene succinate. Such plastics can be slow to degrade in soils due to a lack of efficient polyester degrading organisms. AmCut also showed potential for the biocatalytic synthesis of esters by reverse hydrolysis.

The gene for AmCut has an upstream leader sequence whose transcript is not present in the purified enzyme. In this study, we show using predictive modelling, that this sequence codes for an N-terminal signal peptide that directs transmembrane expression via the Sec secretion pathway.

E. …

Ultrasound 96 Probe Device Protocol For Cancer Cell Treatment, Aisling Field, Brijesh K. Tiwari, James F. Curtin, Julie R M Mondala, Janith Wanigasekara

Articles

Ultrasound is a sound wave with frequencies ranging between 20 kHz and 20 MHz. Ultrasound is able to temporarily and repeatedly open the BBB safely and enhance chemotherapeutic delivery without adverse effects. This novel technique in drug delivery benefits from the powerful ability of ultrasound to produce cavitation activity. Cavitation is the generation and activity of gas-filled bubbles in a medium exposed to ultrasound. As the pressure wave passes through the media, gas bubbles expand at low pressure and contract at high pressure. This leads to oscillation which produces a circulating fluid flow known as microstreaming around the bubble with …

Plasma Induced Reactive Oxygen Species-Dependent Cytotoxicity In Glioblastoma 3d Tumourspheres, Janith Wanigasekara, Carlos Barcia, Patrick J. Cullen, Brijesh Tiwari, James F. Curtin

Articles

The aim of this study was to determine the effects of a pin‐to‐plate cold atmospheric plasma (CAP) on U‐251 MG three‐dimensional (3D) glioblastoma spheroids under different conditions. 3D tumorspheres showed higher resistance to the CAP treatment compared to 2D monolayer cells. A single CAP treatment was able to induce cytotoxicity, while multiple CAP treatments augmented this effect. CAP was also able to induce cytotoxicity throughout the tumoursphere, and we identified that reactive oxygen species(ROS) plays a major role, while H2O2plays a partial role in CAP‐induced cytotoxicity in tumour-spheres. We conclude that ROS‐dependent cytotoxicity is induced uniformly throughout glioblastoma and epidermoid …

Copper(Ii) And Silver(I)‑1,10‑Phenanthroline‑5,6‑Dione Complexes Interact With Double‑Stranded Dna: Further Evidence Of Their Apparent Multi‑Modal Activity Towards Pseudomonas Aeruginosa, Anna Clara Milesi Galdino, Lívia Viganor, Matheus Mendonça Pereira, Michael Devereux, Malachy Mccann, Marta Helena Branquinha, Zara Molphy, Sinéad O'Carroll, Conor Bain, Georgia Menounou, Andrew Kellett, André Luis Souza Dos Santos

Articles

Tackling microbial resistance requires continuous efforts for the development of new molecules with novel mechanisms of action and potent antimicrobial activity. Our group has previously identified metal-based compounds, [Ag(1,10-phenanthroline-5,6-dione)2]ClO4 (Ag-phendione) and [Cu(1,10-phenanthroline-5,6-dione)3](ClO4)2.4H2O (Cu-phendione), with efficient antimicrobial action against multidrug-resistant species. Herein, we investigated the ability of Ag-phendione and Cu-phendione to bind with double-stranded DNA using a combination of in silico and in vitro approaches. Molecular docking revealed that both phendione derivatives can interact with the DNA by hydrogen bonding, hydrophobic and electrostatic interactions. Cu-phendione exhibited the highest binding affinity to either major (− 7.9 kcal/mol) or minor (− 7.2 kcal/mol) …

Converging Technologies: Targeting The Hallmarks Of Cancer Using Ultrasound And Microbubbles, Janith Wanigasekara, Andressa Maria Aguiar De Carvalho, Patrick J. Cullen, Brijesh Tiwari, James F. Curtin

Articles

Various complex biological effects occur when ultrasonic compression waves travel through biological material. The myriad of biological outcomes instigated by ultrasound are evident when viewed through the lens of the hallmarks of cancer. Herein, we summarise the therapeutic potential of ultrasound, enhanced by microbubbles, for the treatment of cancer.

Novel Facet Of An Old Dietary Molecule? Direct Influence Of Caffeine On Glucose And Biogenic Amine Handling By Human Adipocytes, Wiem Haj Ahmed, Nathalie Boulet, Anaïs Briot, Barry J. Ryan, Gemma K. Kinsella, Jeffrey O’Sullivan, Francisco Les, Josep Mercader-Barceló, Gary T. Henehan, Christian Carpéné

Articles

Caffeine is a plant alkaloid present in food and beverages consumed worldwide. It has high lipid solubility with recognized actions in the central nervous system and in peripheral tissues, notably the adipose depots. However, the literature is scant regarding caffeine’s influence on adipocyte functions other than lipolysis, such as glucose incorporation into lipids (lipogenesis) and amine oxidation. The objective of this study was to explore the direct effects of caffeine and of isobutylmethylxanthine (IBMX) on these adipocyte functions. Glucose transport into fat cells freshly isolated from mice, rats, or humans was monitored by determining [3H]-2-deoxyglucose (2-DG) uptake, while the incorporation …

Β-Glucosidase From Streptomyces Griseus: Ester Hydrolysis And Alkyl Glucoside Synthesis In The Presence Of Deep Eutectic Solvents, Albert Uhoraningoga, Gemma K. Kinsella, Gary T. Henehan, Barry J. Ryan

Articles

Deep Eutectic Solvents (DES) are ionic liquid analogs that have attracted considerable attention as green solvents for biocatalytic transformations. The use of DES as part of a ‘solvent engineering’ approach to enhance enzyme stability holds great promise since they are biodegradeable, relatively inexpensive and environmentally safe media for enzyme reactions. However, the behaviour of specific enzymes in such solvents is complex; some enzymes are inhibited in DES, while others appear to be activated.

Glucosidases are among the most widely used enzymes for commercial chemoenzymatic synthesis. In particular, their application in the synthesis of biodegradable alkyl glucosides by reverse hydrolysis is …

Monitoring Stem Cell Differentiation Using Raman Microspectroscopy: Chondrogenic Differentiation, Towards Cartilage Formation, Francesca Ravera, Esen Efeoglu, Hugh Byrne

Articles

Mesenchymal Stem Cells (MSCs) have the ability to differentiate into chondrocytes, the only cellular components of cartilage and are therefore ideal candidates for cartilage and tissue repair technologies. Chondrocytes are surrounded by cartilage-like extracellular matrix (ECM), a complex network rich in glycosaminoglycans, proteoglycans, and collagen, which, together with a multitude of intracellular signalling molecules, trigger the chondrogenesis and allow the chondroprogenitor to acquire the spherical morphology of the chondrocytes. However, although the mechanisms of the differentiation of MSCs have been extensively explored, it has been difficult to provide a holistic picture of the process, in situ. Raman Micro Spectroscopy (RMS) …

Structure Based Prediction Of A Novel Gpr120 Antagonist Based On Pharmacophore Screening And Molecular Dynamics Simulations, Ajay Pal Mr, James Curtin, Gemma K. Kinsella

Articles

The G-protein coupled receptor, GPR120, has ubiquitous expression and multifaceted roles in modulating metabolic and anti-inflammatory processes. Recent implications of its role in cancer progression have presented GPR120 as an attractive oncogenic drug target. GPR120 gene knockdown in breast cancer studies revealed a role of GPR120-induced chemoresistance in epirubicin and cisplatin-induced DNA damage in tumour cells. Higher expression and activation levels of GPR120 is also reported to promote tumour angiogenesis and cell migration in colorectal cancer. Some agonists targeting GPR120 have been reported, such as TUG891 and Compound39, but to date development of small-molecule inhibitors of GPR120 is limited. …

Isolation And Characterization Of A Novel Thermo-Solvent-Stable Lipase From Pseudomonas Brenneri And Its Application In Biodiesel Synthesis, Priyanka Priyanka, Gemma K. Kinsella, Gary T. Henehan, Barry J. Ryan

Articles

Pseudomonads are one of the most studied species of bacteria as they display remarkable metabolic and physiological versatility. This enables them to colonize a wide variety of terrestrial and aquatic habitats, generating biotechnologically interesting enzymes. Here, the partial purification and characterization of a novel, extracellularly-produced, lipase from Pseudomonas brenneri is described. The partially purified lipase was active over a broad pH range (5.0–9.0) and was stable at 70 °C for 45 min. The lipase displayed significant stability, and in some cases activation, in the presence of organic solvents with log P≥2.0. Such stability characteristics indicated that this lipase could potentially …

Enzymatic In-Situ Transesterification Of Neutral Lipids From Simulated Wastewater Cultured Chlorella Emersonii And Pseudokirchneriella Subcapitata To Sustainably Produce Fatty Acid Methyl Esters, Priyanka Priyanka, Gemma K. Kinsella, Gary Henehan, Barry J. Ryan

Articles

Alternative, more sustainable and environmentally positive, sources of energy are one of the current global challenges. One approach to achieving more sustainable sources of energy is to use waste from one system as a raw material for energy production, following the circular biosystem philosophy. This study successfully adopted this approach whereby microalgae strains Chlorella emersonii and Pseudokirchneriella subcapitata were bioprospected and metabolically engineered in simulated wastewater supplemented with glucose to produce neutral lipids. Using a two-step cultivation approach neutral lipid content was enhanced in Chlorella emersonii and Pseudokirchneriella subcapitata biomass. Via in-situ transesterification, these neutral lipids were subsequently bioconverted to …

Methylxanthines Inhibit Primary Amine Oxidase And Monoamine Oxidase Activities Of Human Adipose Tissue, Wiem Haj Ahmed, CéCile Peiro, Jessica Fontaine, Barry J. Ryan, Gemma K. Kinsella, Jeff O’Sullivan, Jean-Louis Grolleau, Gary T.M. Henehan, Christian CarpéNé

Articles

Abstract: Background: Methylxanthines including caffeine and theobromine are widely consumed compounds and were recently shown to interact with bovine copper-containing amine oxidase. To the best of our knowledge, no direct demonstration of any interplay between these phytochemicals and human primary amine oxidase (PrAO) has been reported to date. We took advantage of the coexistence of PrAO and monoamine oxidase (MAO) activities in human subcutaneous adipose tissue (hScAT) to test the interaction between several methylxanthines and these enzymes, which are involved in many key pathophysiological processes. Methods: Benzylamine, methylamine, and tyramine were used as substrates for PrAO and MAO in homogenates …

Cold Atmospheric Plasma Induces Silver Nanoparticle Uptake, Oxidative Dissolution And Enhanced Cytotoxicity In Glioblastoma Multiforme Cells, Eline Manaloto, Aoife Gowen, Anna Lesniak, Zhonglei He, Alan Casey, Patrick J. Cullen, James Curtin

Articles

Silver nanoparticles (AgNP) emerged as a promising reagent for cancer therapy with oxidative stress implicated in the toxicity. Meanwhile, studies reported cold atmospheric plasma (CAP) generation of reactive oxygen and nitrogen species has selectivity towards cancer cells. Gold nanoparticles display synergistic cytotoxicity when combined with CAP against cancer cells but there is a paucity of information using AgNP, prompting to investigate the combined effects of CAP using dielectric barrier discharge system (voltage of 75 kV, current is 62.5 mA, duty cycle of 7.5kVA and input frequency of 50–60Hz) and 10 nm PVA-coated AgNP using U373MG Glioblastoma Multiforme cells. Cytotoxicity in …

Synthesis And Optimisation Of P3 Substituted Vinyl Sulfone-Based Inhibitors As Anti-Trypanosomal Agents, William Doherty, Nikoletta Adler, Andrew Knox, Thomas J. Butler, Paul Evans

Articles

A series of lysine-based vinyl sulfone peptidomimetics were synthesised and evaluated for anti-trypanosomal activity against bloodstream forms of T. brucei. This focused set of compounds, varying in the P3 position, were accessed in a divergent manner from a common intermediate (ammonium salt 8). Several P3 analogues exhibited sub-micromolar EC50 values, with thiourea 14, urea 15 and amide 21 representing the most potent anti-trypanosomal derivatives of the series. In order to establish an in vitro selectivity index the most active anti-trypanosomal compounds were also assessed for their impact on cell viability and cytotoxity effects in mammalian cells. Encouragingly, all compounds only …

Optimisation Of Estrogen Receptor Subtype-Selectivity Of A 4-Aryl-4h-Chromene Scaffold Previously Identified By Virtual Screening, Miriam Carr, Andrew Knox, Daniel Nevin, Niamh O'Boyle, Shu Wang, Billy Egan, Thomas Mccabe, Brendan Twamley, Daniela Zisterer, David Lloyd, Mary Meegan

Articles

4-Aryl-4H-Chromene derivatives have been previously shown to exhibit anti-proliferative, apoptotic and anti-angiogenic activity in a variety of tumor models in vitro and in vivo generally via activation of caspases through inhibition of tubulin polymerisation. We have previously identified by Virtual Screening (VS) a 4-aryl-4H-chromene scaffold, of which two examples were shown to bind Estrogen Receptor α and β with low nanomolar affinity and <20-fold selectivity for α over β and low micromolar anti-proliferative activity in the MCF-7 cell line. Thus, using the 4-aryl-4H-chromene scaffold as a starting point, a series of compounds with a range of basic arylethers at C-4 and modifications at the C3-ester substituent of the benzopyran ring were synthesised, producing some potent ER antagonists in the MCF-7 cell line which were highly selective for ERα (compound 35; 350-fold selectivity) or ERβ (compound 42; 170-fold selectivity).

Characterization Of An Aryl Piperazine/2-Hydroxypropyl-Β-Cyclodextrin Association, A Complex With Antidiabetic Potential, R. Devine, D.S.D. Martin, Gemma Kinsella, J.B.C. Findlay, J.C. Stephens

Articles

This study explores the molecular association between 4-(thiophen-2-yl)-1-(4-(4-(trifluoromethyl)phenyl)piperazin-1-yl)butan-1-one (RTC1), an antidiabetic compound recently reported by our research group with challenging aqueous solubility, and 2-hydroxypropyl-β-cyclodextrin (HPBCD). The formation of a RTC1/HPBCD complex resulted in improved solubility. A phase-solubility diagram was used to determine the complex stability constant and stoichiometric ratio. 2D ¹H NMR spectroscopy was utilized to study the molecular interaction between RTC1 and HPBCD in the complex. Differential scanning calorimetry and scanning electron microscopy was also employed to confirm complex formation. In vitro biological evaluation, using a glucose uptake assay, showed that the homogeneous RTC1/HPBCD complex solution showed the …

Determining The Age Of Spoiled Milk From Dried Films Using Attenuated Reflection Fourier Transform Infrared (Atr Ft-Ir) Spectroscopy, Zack Richardson, David Perezguaita, Kamila Kochan, Bayden Wood

Articles

Milk spoilage is an inevitable occurrence, which generates waste and can result in food poisoning. When milk spoils, the off-flavor and curdling are due to excessive proliferation of various bacteria which causes pH changes. Time, temperature, environment,and previous handling practice all affects the spoilage rate. There is a need for a fast reliable and accurate method that can identify in situearly spoilage of milk. Here we show the ability of attenuated total reflectionFourier transformed infrared spectroscopy(ATR FT-IR) in conjunction with multivariate data analysis to predict the age of milk. We found that dried films vastly increased the absorbance of important …

Cold Atmospheric Plasma Stimulates Clathrin-Dependent Endocytosis To Repair Oxidised Membrane And Enhance Uptake Of Nanomaterial In Glioblastoma Multiforme Cells, Zhonglei He, Kangze Li, Laurence Scally, Eline Manaloto, Sebnem Gunes, Sing Wei Ng, Marcus Maher, Brijesh Tiwari, Hugh Byrne, Paula Bourke, Furong Tian, Patrick Cullen, James Curtin

Articles

Cold atmospheric plasma (CAP) is increasingly studied in a growing number of clinical trials for cancer treat-ment1,2 and research is ongoing to explore the combination of CAP with other therapies, including nanoparticles, radiotherapy and chemotherapy3–5.Gold nanoparticles (AuNPs) are known to be weakly-toxic to human cells and be readily manufactured and designed for targeting delivery of various therapeutic compounds into cells. Citrate-capped cationic AuNPs may adsorb serum proteins onto their surface and thereby stimulate receptor-mediated endocytosis6. Without special surface functionalisation, AuNPs enter cells and become trapped in vesicles6–8 or enter the nucleus, depending on their size/shape9,10. Meanwhile, AuNPs with functionalised surface …

A Novel Pool Of Microparticle Cholesterol Is Elevatedin Rheumatoid Arthritis But Not In Systemic Lupus Erythematosus Patients, Shuai Shuai Hu, Brenton L. Cavanagh, Robert Harrington, Muddassar Ahmad, Grainne Kearns, Steve Meaney, Claire Wynne

Articles

Microparticles are sub-micron, membrane-bound particles released from virtually allcells and which are present in the circulation. In several autoimmune disorders their amountand composition in the circulation is altered. Microparticle surface protein expression has beenexplored as a differentiating tool in autoimmune disorders where the clinical pictures can overlap.Here, we examine the utility of a novel lipid-based marker—microparticle cholesterol, present in allmicroparticles regardless of cellular origin—to distinguish between rheumatoid arthritis (RA) andsystemic lupus erythematosus (SLE). We first isolated a series of microparticle containing lipoproteindeficient fractions from patient and control plasma. There were no significant differences in thesize, structure or protein content of …

Extraction Of Protein From Four Different Seaweeds Using Three Different Physical Pre-Treatment Strategies, Jack O'Connor, Steve Meaney, Gwilym A. Williams, Maria Hayes

Articles

Seaweeds are a rich source of protein and can contain up to 47% on the dry weight basis. It ischallenging to extract proteins from the raw biomass of seaweed due to resilient cell-wall complexes.Four species of macroalgae were used in this study-two brown,Fucus vesiculosusandAlaria esculenta,and two red,Palmaria palmataandChondrus crispus. Three treatments were applied individually tothe macroalgal species: (I) high-pressure processing (HPP); (II) laboratory autoclave processing and(III) a classical sonication and salting out method. The protein, ash and lipid contents of the resultingextracts were estimated. Yields of protein recovered ranged from 3.2% forFucus vesiculosuspre-treatedwith high pressure processing to 28.9% protein recovered …

Impact Of Cold Plasma Processing On Major Peanut Allergens, Harshitha Venkataratnam, Orla Cahill, Chaitanya Sarangapani, Patrick Cullen, Catherine Barry-Ryan

Articles

Cold plasma is emerging as a novel food processing technology, with demonstrated efficacies for microbial inactivation and residual chemical dissipation of food products. Given the technology’s multimodal action it has the potential to reduce allergens in foods, however data on the efficacy and mechanisms of action are sparse. This study investigates the efficacy of cold plasma on major peanut allergens (Ara h 1 and Ara h 2). For this purpose, dry, whole peanut (WP) and defatted peanut flour (DPF) were subjected to an atmospheric air discharge using a pin to plate cold plasma reactor for different treatment durations. With increases …

Pt(Iv) Pro-Drugs With An Axial Hdac Inhibitor Demonstrate Multimodal Mechanisms Involving Dna Damage And A Poptosis Independent Of Cisplatin Resistance In A2780/A2780cis Cells, Awatif Rashed Z. Almotairy, Diego Montagner, Liam Morrison, Michael Devereux, Orla Howe, Andrea Erxlebena

Articles

Epigenetic agents such as histone deacetylase (HDAC) inhibitors are widely investigated for use in combined anticancer therapy and the co-administration of Pt drugs with HDAC inhibitors has shown promise for the treatment of resistant cancers. Coordination of an HDAC inhibitor to an axial position of a Pt(IV) derivative of cisplatin allows the combination of the epigenetic drug and the Pt chemotherapeutic into a single molecule. In this work we carry out mechanistic studies on the known Pt(IV) complex cis,cis,trans-[Pt(NH3)2Cl2(PBA)2] (B) with the HDAC inhibitor 4-phenylbutyrate (PBA) and its derivatives cis,cis,trans-[Pt(NH3)2Cl2(PBA)(OH)] (A), cis,cis,trans-[Pt(NH3)2Cl2(PBA)(Bz)] (C), and cis,cis,trans-[Pt(NH3)2Cl2(PBA)(Suc)] (D) (Bz = benzoate, Suc …

The Effect Of Calcium Alginate Entrapment On The Stability Of Novel Lipases From P. Reinekei And P. Brenneri, Priyanka Priyanka, Gemma K. Kinsella, Gary T. Henehan, Barry J. Ryan

Articles

The high cost of soluble enzymes can limit their use for commercial and industrial purposes. Immobilization can enhance enzyme reusability, thereby reducing product isolation costs and overcoming this economic barrier. In the current study, two novel, purified lipases from Pseudomonas sp. (Pseudomonas reinekei and Pseudomonas brenneri) were entrapped in a calcium alginate matrix, with the aim of simultaneously enhancing enzyme reusability and stability. Following entrapment, the retained activity of the enzyme-alginate composite was verified by an enzymatic hydrolysis reaction of a p-nitrophenol palmitate substrate. The effect of the enzyme-alginate entrapment against various physiochemical parameters such as pH, temperature, metal ions, …

Cold Atmospheric Plasma Induces Accumulation Of Lysosomes And Caspase-Independent Cell Death In U373mg Glioblastoma Multiforme Cells, Gillian Conway, Zhonglei He, Ana L. Hutanu, George P. Cribaro, Eline Manaloto, Alan Casey, Damien Traynor, Vladimir Milosavljevic, Orla Howe, Carlos Barcia, James T. Murray, Patrick Cullen, James Curtin

Articles

Room temperature Cold Atmospheric Plasma (CAP) has shown promising efficacy for the treatment of cancer but the exact mechanisms of action remain unclear. Both apoptosis and necrosis have been implicated as the mode of cell death in various cancer cells. We have previously demonstrated a caspase-independent mechanism of cell death in p53-mutated glioblastoma multiforme (GBM) cells exposed to plasma. The purpose of this study was to elucidate the molecular mechanisms involved in caspase-independent cell death induced by plasma treatment. We demonstrate that plasma induces rapid cell death in GBM cells, independent of caspases. Accumulation of vesicles was observed in plasma …