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Tocilizumab (Actemra®) in COVID-19 Treatment What is Tocilizumab? Tocilizumab, also called atlizumab, is an immunosuppressive humanised monoclonal antibody which targets the IL-6 receptor. IL-6 is a cytokine which is involved in many important immune responses—discussed below— but which can also contribute to the pathogenesis of certain diseases, specifically autoimmune diseases and certain types of cancers. Most notably, IL-6 is implicated in cytokine release syndrome and thus targeting it or its receptor is thought to be a promising therapeutic intervention. window. …

By Francisco Algaba Chueco In this post we discuss a topic that everyone will have heard of. Let’s talk about migraines, a disorder that hides a huge physiological and molecular background, and having an impact alarmingly high around the globe. We are going to enter the etiology of the disease, in all molecular and supramolecular processes that trigger it and we are going to finally talk about the traditional therapies, the most novel therapies and, of course, prophylaxis or prevention of migraines.This post is not intended to be a review, but a somewhat more scientific than is generally known about migraines, explained so that everyone can und …

Oesophageal Adenocarcinoma is on the rise globally affecting more than 450,000 people worldwide (Pennathur, Gibson et al. 2013). Once diagnosed overall 5-year survival ranges from 15 % to 25 %, with the best outcomes being associated diagnosis in the early stages of cancer development (Pennathur, Gibson et al. 2013). Oesophageal Adenocarcinoma (OAC) arises from a pre malignant condition known as Barrett’s Oesophagus (BO). BO is associated with an increased risk of developing OAC compared to normal age matched controls. Barrett’s Oesophagus Barrett’s oesophagus (BO) occurs when the normal squamous epithelium of the oesophagus is replaced by …

By Sophie Arthur How many diseases and conditions do you think exist in this world? Thousands? Hundreds of thousands? Maybe even millions? Unfortunately, I don’t know the answer. But what I do know is there could be one solution to all of them! Yes, one perfect medicine of the future! The answer? Stem cells! Stem cells, promises & superheroes Our bodies are made up of an extraordinary amount of cells – all with their own unique shape, function and gene expression, and one of the reasons there are so many diseases we need to know how to treat! But where did all these trillions of cells in our body come from? Well, we all had the same humble beginnings when we were all just a teen …

Sarah Brun Bar-Yaacov PhD Candidate, University of Liverpool Orthohantaviruses are a group of segmented negative-sense RNA viruses maintained as asymptomatic infections in rodent, insectivore and bat populations (Vaheri, Strandin, et al. 2013). They are Bunyaviruses and to date 41 orthohantavirus species have been officially recognized (ICTV 2014). Among orthohantaviruses, the rodent-borne are the most studied, as these are the only ones associated with human disease. Orthohantaviruses are found in endemic regions across the globe. Each viral species is closely associated with a specific carrier host and the presence of a specific virus in a …

By Sinead Kinsella PhD The Ubiquitin Proteasome System (UPS) The Ubiquitin Proteasome System (UPS) is a regulatory machinery for protein turnover in the cell (Pickart, 2001), and strict regulation of the balance between protein synthesis and degradation is essential for cellular homeostasis (Gaczynska et al., 2001). The UPS is composed of the ubiquitination system, which governs the labelling of proteins for degradation, and the proteasome, which carries out protein degradation (Jansen et al., 2014). Ubiquitin degradation is a highly regulated process with specific targeting of the protein with ubiquitin molecules prior to degradation by the …

The Enteric Nervous system (ENS) is one of the largest subdivisions of the Peripheral Nervous System. This remarkable system is embedded between sheets of smooth muscle cells of the intestinal tissue. It is also called as the “second brain” as it consists of millions of neurons that coalesce to form its vast network. The ENS originates from neural crest-derived progenitors that traverse through different spatio-temporal environments, expanding in number, colonizing the gut tissue and eventually generating a diverse array of neuronal and glial subtypes. The ENS is indispensable for key functions of gut physiology such as peristalsis, secretion of enzymes and absorption of food. It is …

Protein kinase B or AKT (PKB) is a serine/threonine kinase. In mammals it is comprised of 3 highly homologous isoforms PKBα (Akt1), PKBβ (Akt2), and PKBγ (Akt3) (Manning and Cantley 2007). AKT signalling is activated in response to a variety of hormones, growth factors and extracellular matrix (ECM) components. The serine/threonine kinase AKT is involved in the regulation of a number of cellular processes including cell growth, proliferation, metabolism and cell survival. AKT Signalling Activation AKTs are activated by receptor tyrosine kinases (RTKs). RTKs activate phosphatidylinositol 3-kinase (PI3K) through tyrosine phosphorylation of adaptor proteins …

HMGB1 Functional Overview High mobility group box 1 ( HMGB1), a member of the high-mobility group (HMG) family, was first identified in the thymus in 1973 and is classified as a non-histone DNA-binding protein (Goodwin et al., 1973). HMGB1, a 215 amino-acid protein, is structurally composed of two HMG-box domains, which are DNA-binding, and C-terminal tail which facilitates protein-protein interactions (Park et al., 2004; Stros et al., 2010). Nuclear HMGB1 acts as a DNA chaperone and contributes to several regulatory processes in the nucleus such as transcriptional stability, nucleosome assembly and DNA replication (Agresti et al., 2003; Reeves et a …

Thanks to the great intuitions of brilliant scientists like Louis Pasteur, Edward Jenner, Robert Koch, Emil von Behring, Gaston Leon Ramon, Albert Sabin, Jonas Salk in the past century, the world has gotten to know the super power inside every individual: THE IMMUNE SYSTEM. “Find a pathogen, isolate it, kill it and inject it in the host…… the rest is left to our immune system”. Thanks to that concept, microorganisms like Yersinia pestis, Spanish flu and many others responsible of devastating society provoking millions of deaths were finally facing the end of their days thanks to a very simple, yet new concept developed by the greatest minds of the past century“ Vaccination”. Thi …

Pancreatic cancer survival rates Despite recent advances in our understanding of this disease, pancreatic cancer is one of the world’s most lethal malignancies. Although the disease accounts for only about 3% of all cancers, it is regarded as the 7th leading cause of cancer related deaths worldwide (Siegel, R et al., 2019). Worryingly, the overall 5-year survival rate for pancreatic cancer is less than 6%; where most patients die within 3 to 8 months after diagnosis and can be regarded as the ultimate death penalty. Chemoresistance and radioresistance are leading to tumour recurrence and metastatic lesions with enhanced aggressiveness, and …

The Complement System Function Gone are the days when the complement system was considered solely a companion of its impressive adaptive immune system counterpart. Research in recent decades has demonstrated that complement cascade components play intricate roles in processes spanning from traditional innate defence to angiogenesis, bone metabolism and neural development. These ultimately homeostatic activities demonstrate that the complement system as a whole adopts a key role in immune surveillance (Ricklin et al., 2010; Reis et al., 2018). What was once thought to be a single protein responsible for enhancing antibody-mediated lysis of target ce …

By Dr. Lisa Dwane, Postdoctoral Researcher, Royal College of Surgeons in Ireland The first link between estrogen and breast cancer was made in the late 1800s, when physician George Beatson, who correctly suspected a link between the endocrine system and breast cell proliferation, removed the ovaries of a 33-year old woman with advanced breast cancer and controlled the growth of her tumours (Clarke, 1998). The young mother astonishingly lived for four years following this surgery; an unheard miracle in an era that offered toxic chemotherapy and debilitating surgical procedures as the only options for advanced cancer. Over a century later our …

By Rachel Bleach, PhD Student, RCSI By the age of 79 years, 1 in 14 women will develop breast cancer (Global Burden of Disease Cancer 2017). Beatson reported on the utility of removing the ovaries in the treatment of advanced breast cancer in 1896, leading to the observation that estrogen is one of the driving factors in breast cancer. This discovery revolutionised the field for breast cancer treatments and since then, there has been a firm focus on estrogen ablation as a therapy (Love and Philips 2002). Initially therapies such as selective estrogen receptor modulators/degraders were developed to target the estrogen receptor (ER) protein. More rece …

The immune system is the body’s main defence against infection. In order to function properly, the immune system must be able to detect and protect against infinite agents such as pathogens including viruses and bacteria and unhealthy or infected cells. In order to do this, various cells are required to carry out specific functions. In the article below, an overview of neutrophils will be discussed including their function and development. What is a Neutrophil? Neutrophils are the most abundant white blood cell in the circulation are regarded as the first line of defence of the innate immune system. They are characte …

BRIEF HISTORY OF THE “GREEN” EVOLUTION OF OXYGEN AND CARBON DIOXIDE WITHIN OUR ATMOSPHERE Million years ago carbon dioxide (CO2) levels used to be considerably higher compared to the measured levels today (Allègre and Schneider, 1994) (see Figure 1). Notably, the Mauna Loa Observatory in Hawaii repeatedly measured unprecedented inclines of CO2 levels over the last years with recent peaks of more than 400 ppm (i.e., atmospheric concentrations of 0.04%) (National Oceanic and Atmospheric Administration, 2019). window.SHOGUN_IMAGE_ELEMENTS = window.SHOGUN_IMAGE_ELEMENTS || new Array(); window.SHOGUN_I …

Dr. Melissa Conroy, TTMI I am an immunologist and senior research fellow in the Cancer Immunology and Immunotherapy Group, Department of Surgery at Trinity College Dublin. My research is focused on developing novel immunotherapies in the space of obesity, cancer and liver disease with a specific focus on lymphocyte trafficking and chemokine networks. My research examines how we can target the underlying immune processes in pathological inflammation in obesity, cancer and liver disease. My PhD was focused on immune responses to chronic hepatitis virus infection and identified novel functions of natural killer cells and innate T cells in viral hepa …

By Eoin Mac Réamoinn Toll-like receptors (TLRs) are renowned for their fundamental roles in innate sensing and initiating inflammatory responses. TLRs accomplish this remarkable task through interactions with conserved molecular structures known as pathogen-associated molecular patterns (PAMPs), such as lipopolysaccharides, that are expressed by microbial species. Once ligated, TLRs propagate stimuli via one of two intracellular signalling cascades culminating in the induced expression of pro-inflammatory genes needed for pathogen clearance and tissue remodelling. The Architecture of a Toll-like receptor …

Katherine Edwards, PhD Student, Queen’s University Belfast Cytokines play a vital role in immune responses enabling cross-talk between different cell types and inducing activation, differentiation, proliferation and cell migration by altering gene expression in target cell types. There are a wide variety of cytokines each with varying roles which when produced in different combinations can lead to various outcomes. Cytokines can promote inflammation and aid migration of effector immune cells to sites of infection or damage where these cells then work as a team to combat the problem. Cytokines can also be anti-inflammatory – these cytokines are relea …

Traumatic injuries & death When I ask people what the leading cause of death is in the United States in people age 44 and under, they generally reply saying cancer. It wouldn’t be illogical to think that this is the answer, but it would be incorrect. In fact, unintentional traumatic injuries are responsible for more deaths in these age groups than any other cause such as homicide, cancer or heart disease. Accidental traumatic injury can be categorized into several groups such as blunt-force trauma, hemorrhage, crush injuries, bone fractures, radiation injury and any of these in combination. These types of injuries happen in traumatic scenarios like …

Laura Menke PhD candidate, Queen Mary University of London Inflammation vs. Resolution Atherothrombosis is the leading cause of death worldwide and can be linked to the formation of blood clots in the vascular system. Depending on the location of clot formation, atherothrombosis can stimulate a variety of disease pathologies such as stroke, heart infarct and even leg ischemia, which makes research regarding prevention and treatment of this disease so important. Epidemiological studies indicate that in our society with increased age and enhanced obesity and diabetes prevalence, the risk of vascular diseases will further increase and reac …

By Sonika Singh PhD candidate, University of Nottingham A Devastating Disease Multiple Sclerosis (MS) is a chronic and inflammatory disease based on autoimmunity[1], mainly affecting the central nervous system (CNS) in young white adults[2]. MS is a disease which involves damage to the myelin sheath, that is a lipoprotein-based insulation of the axons. This sheath is essential for the electrical activity and saltatory conduction of nerve impulses and is an important part of the nervous system [2]. Areas of inflammation, axonal loss, demyelination and gliosis, occurring throughout the brain and spinal cord are the distinctive features o …

Interferons (IFNs) are a group of signalling proteins that are produced and released from cells in response to viral infection and other stimuli such as normal and tumour cell survival and death. IFNs interact with specific cellular receptors, thereby promoting production of secondary messengers which leads to the expression of antiviral and immune modulatory genes. There are three groups of IFNs, Type I IFNs, Type II IFNs and Type III IFNs. Type I IFNs include IFN-alpha, -beta, -omega, -kappa and IFN-zeta. These are essential for regulating the immune response to viral infections. The Type II IFN group only includes IFN-gamma. IFN-gamma is a versatile cytokine that plays an essen …

LATS kinases belong to a family of proteins that, in mammals, are comprised of two isoforms, LATS1 and LATS2. Originally identified in Drosophila melanogaster as Warts kinase, LATS1 and LATS2 serine/threonine kinases have been shown to be tumour suppressors (Edwards and Munger 2004). The original homologue of LATS was described as the dlats/warts tumour suppressor in two independent screens in Drosophila (Justice et al. 1995, Xu et al. 1995). Dlats and warts encoded the same gene so in this thesis the original homologue of LATS is warts (wts). Homozygous loss of the warts gene in Drosophila formed greatly overgrown somatic cells which lead to the hypothesis that warts is a tumour suppr …