AGE-RAGE stress: the importance of AGE/sRAGE ratio studied in various diseases. Part III. RAGE and individual diseases states, aging and senescence

Advanced glycation end products (AGEs) and their mRAGE receptor play an important role in the pathogenesis of metabolic diseases. AGEs modify proteins and interact with RAGE with subsequent activation of various signaling pathways, including induction of oxidative stress and resulting activation of nuclear factor NFk-B with subsequent inflammatory response. AGE-RAGE axis, along with other mechanisms, is involved in the pathogenesis of later diabetic complications. The role of RAGE in various clinical situations is currently being intensively studied. AGEs and RAGE alone do not appear to serve as a universal biomarker. On the other hand, the soluble AGEs receptor (sRAGE) neutralizes unwanted interactions by competitive binding with AGEs and may be a potential protective factor in the development of some diseases. Low levels of sRAGE have been suggested as a biomarker of diseases other than diabetes mellitus and kidney disease (where sRAGE levels are elevated). Circulating sRAGE levels can be increased or even decreased in various diseases while increasing AGE levels. sRAGE can serve as a biomarker of disease incidence and adverse symptoms or as a prognostic biomarker of irreversible homeostasis or mortality. It seems practical to evaluate the so-called AGE-RAGE stress as the ratio of measured circulating AGEs/sRAGE levels. An increased AGEs/sRAGE ratio may be a universal or risk biomarker. Based on promising experimental results, mRAGE alone may be a therapeutic target in some diseases (Fig. 2, Ref. 107). Text in PDF www.lekarsky.herba.sk. © 2023, Lekarsky Obzor. All Rights Reserved.

Relationship between Severe Acute Respiratory Syndrome Coronavirus 2 and Diabetes Mellitus (Review)

Infections caused by SARE- CoV-2 are complicated with the concurrent pathologies, to name hypertension, diabetes mellitus and cardiovascular diseases. High level of glucose in blood weakens the immunity and increase the SARS-CoV-2 replication. Diabetes mellitus aggravates the COVID-19 outcome. The intrusion of SARS-CoV-2 into a host-cell occurs by means of its association with the angiotensin-converting enzyme-2 (ACE 2). Stimulating immune responses the COVID-19 infection causes the cytokine storm, and may result in the lethal outcome in the diabetics. Recent laboratory studies demonstrated that the type1 and type2 diabetes mellitus is the main consequence in 14% of the patients after corona infection. Thus, in 2% of 14% diabetes started progressing due to the corona virus. In the other, diabetes debut occurred as the direct and negative consequence of the disease. Hyperglycemia results in the formation of protein molecules known as the advanced glycation end products (AGEs). The AGEs and their receptors (RAGE) are of high significance in the host-cell's virus invasion. Consequently, more strict glucose control is necessary for optimal outcome and reduction in mortality. The better control for the COVID-19 course can be provided by the targeted effect on the RAGE axis. The review helps elucidate the molecular mechanism underlying the exacerbation of pathophysiology in the diabetic COVID-19 patients.

Did COVID-19 Make Me an Afro-Pessimist? A Conversation in Three Parts

As the COVID-19 pandemic continues to rage and disproportionately affect BIPOC, we keep count of the death toll around the world, in the U.S., in our own communities and in our own families. How can we have a "wish to live,” while so many around us die? Does a space exist between fateful (faithful) optimism present in Aretha Franklin's, "Mary Don't You Weep?” and the ever-present power structure, that as Reverend Al Sharpton noted, has always had its knee on our necks? More concretely, how do we reconcile what Aisha Durham discusses as "weathering and wounded,” as we sit in the space of being both and not wanting to endure much more. This piece articulates some of the conversations that we have stumbled upon, worked through and raged against from the space of our collective homes and fatigued spirits. It addresses notions of Afro-Pessimism and the intersection of Black Feminist Theory, the role that grief plays in Black Feminist praxis, the role of Diaspora in the historical imagination, and asks the question, "Did COVID and the state-sanctioned killings of Black people make us Afro-Pessimists?”

RAGE Inhibitors in Neurodegenerative Diseases.

Nonenzymatic reactions of reducing sugars with primary amino groups of amino acids, proteins, and nucleic acids, followed by oxidative degradations would lead to the formation of advanced glycation endproducts (AGEs). The AGEs exert multifactorial effects on cell damage leading to the onset of neurological disorders. The interaction of AGEs with the receptors for advanced glycation endproducts (RAGE) contribute to the activation of intracellular signaling and the expression of the pro-inflammatory transcription factors and various inflammatory cytokines. This inflammatory signaling cascade is associated with various neurological diseases, including Alzheimer's disease (AD), secondary effects of traumatic brain injury (TBI), amyotrophic lateral sclerosis (ALS), and diabetic neuropathy, and other AGE-related diseases, including diabetes and atherosclerosis. Furthermore, the imbalance of gut microbiota and intestinal inflammation are also associated with endothelial dysfunction, disrupted blood-brain barrier (BBB) and thereby the onset and progression of AD and other neurological diseases. AGEs and RAGE play an important role in altering the gut microbiota composition and thereby increase the gut permeability and affect the modulation of the immune-related cytokines. The inhibition of the AGE-RAGE interactions, through small molecule-based therapeutics, prevents the inflammatory cascade of events associated with AGE-RAGE interactions, and thereby attenuates the disease progression. Some of the RAGE antagonists, such as Azeliragon, are currently in clinical development for treating neurological diseases, including AD, although currently there have been no FDA-approved therapeutics based on the RAGE antagonists. This review outlines the AGE-RAGE interactions as a leading cause of the onset of neurological diseases and the current efforts on developing therapeutics for neurological diseases based on the RAGE antagonists.

Effect of COVID-19 on Working Women's Physical and Mental Health: A Descriptive Study of Pre and Post Pandemic Era

Background and Aim: In 2019, the World Health Organization (WHO) recognized the coronavirus outbreak as a pandemic and a public health emergency of global significance. Recent studies have revealed that these restrictions and women's anxiety of the virus itself may have had an adverse effect on their mental health. Children and family members are spending more time at home;thus, society needs to be conscious of how this is affecting working women's emotional and physical health especially in the absence of any assisting maid. Thus, the purpose of this study was to evaluate how the COVID-19 pandemic lockdown affected working women's physical and mental health. Material(s) and Method(s): To examine the effects of COVID-19 on the physical and emotional health of working women, a cross-sectional survey was conducted. Data is collected using an online survey platform. To investigate the impact of lockdown on the women's mental and physical health, a semi-structured questionnaire comprising a number of open-and closed-ended questions was prepared. Additionally, any mental health disorders and emotional difficulties that developed during lockdown or became worse were enlisted. Another goal was to gauge how much family members understood and were sympathetic to the physical and mental strain the working women were under. Result(s): The study involved 200 women from different states of India. The hours spent in the kitchen and other associated activities increased from 1.5 hours to 5.5 hours when the time between before and during the lockdown was compared. The amount of time spent engaging in physical activity, such as yoga and morning and evening walks, significantly decreased during the lockdown are coming to normal after the lockdown. 68 per cent of those surveyed said that women's behaviour had changed. About 58 per cent of the women suffered physical changes such fatigue, headaches, lower back discomfort, and other issues with women's weight gain. Conclusion(s): Additional research is required to better understand the long-term effects of the COVID-19 pandemic on women's mental health, particularly in regard to the identification of additional variables that may be connected to the pandemic's potentially multiplicative effects on women.Copyright © 2023, Institute of Medico-legal Publication. All rights reserved.

Dies irae: ¿Por qué las democracias liberales no logran domesticar la ira y la violencia?

El siglo XXI ha estado marcado por innumerables protestas callejeras en diferentes regiones del mundo desatadas a su vez por disímiles coyunturas políticas. El artículo tiene dos objetivos: primero, proponer las emociones políticas de la rabia, el resentimiento y el deseo de reconocimiento como categorías interpretativas de las expresiones de inconformidad ciudadanas frente a la política contemporánea. Segundo, advertir que la incapacidad de las democracias liberales para domesticar la violencia constituye uno de los mayores fracasos de la modernidad política. Así, a partir de la lectura crítica de los filósofos políticos contemporáneos más relevantes en el ámbito occidental, ambos objetivos mostrarán que la crisis de las democracias liberales y del capitalismo tiene raíces estructurales y que demandan la reinvención del paradigma triunfante en 1989 conocido como el Fin de la Historia.Alternate abstract:The 21st century has been marked by countless street protests in different regions of the world that have been unleashed by dissimilable political circumstances. The article has two objectives: first, to propose the political emotions of rage, resentment and desire for recognition as interpretative categories of expressions of citizen dissatisfaction vis-a-vis contemporary politics. Secondly, to warn that the inability of liberal democracies to domesticate violence is one of the greatest failures of political modernity. Thus, from the critical reading of the most relevant contemporary political philosophers in the Western sphere, both objectives will show that the crisis of liberal democracies and capitalism has structural roots and demand the reinvention of the triumphant paradigm in 1989 known as the End of History.

Elevated neutrophil extracellular traps by HBV-mediated S100A9-TLR4/RAGE-ROS cascade facilitate the growth and metastasis of hepatocellular carcinoma.

BACKGROUND: Neutrophil extracellular traps (NETs) are considered significant contributors to cancer progression, especially metastasis. However, it is still unclear whether NETs are involved in hepatitis B virus (HBV)-related hepatocarcinogenesis and have potential clinical significance during evaluation and management for hepatocellular carcinoma (HCC). In this study, we aimed to investigate the functional mechanism of NETs in HBV-related hepatocarcinogenesis and their clinical significance. METHODS: A total of 175 HCC patients with and without HBV infection and 58 healthy controls were enrolled in this study. NETs were measured in tissue specimens, freshly isolated neutrophils and blood serum from these patients, and the correlation of circulating serum NETs levels with malignancy was evaluated. The mechanism by which HBV modulates NETs formation was explored using cell-based studies. In addition, in vitro and in vivo experiments were further performed to clarify the functional mechanism of NETs on the growth and metastasis of HCC. RESULTS: We observed an elevated level of NETs in blood serum and tissue specimens from HCC patients, especially those infected with HBV. NETs facilitated the growth and metastasis of HCC both in vitro and in vivo, which were mainly dominated by increased angiogenesis, epithelial-mesenchymal transition (EMT)-related cell migration, matrix metalloproteinases (MMPs)-induced extracellular matrix (ECM) degradation and NETs-mediated cell trapping. Inhibition of NETs generation by DNase 1 effectively abrogated the NETs-aroused HCC growth and metastasis. In addition, HBV-induced S100A9 accelerated the generation of NETs, which was mediated by activation of toll-like receptor (TLR4)/receptor for advanced glycation end products (RAGE)-reactive oxygen species (ROS) signaling. Further, circulatory NETs were found to correlate with viral load, TNM stage and metastasis status in HBV-related HCC, and the identified NETs could predict extrahepatic metastasis, with an area under the ROC curve (AUC) of 0.83 and 90.3% sensitivity and 62.8% specificity at a cutoff value of 0.32. CONCLUSIONS: Our findings indicated that activation of RAGE/TLR4-ROS signaling by HBV-induced S100A9 resulted in abundant NETs formation, which subsequently facilitated the growth and metastasis of HCC cells. More importantly, the identified circulatory NETs exhibited potential as an alternative biomarker for predicting extrahepatic metastasis in HBV-related HCC.

Enhanced Expression of RAGE AXIS Is Associated with Severity of COVID-19 in Patients with Comorbidities.

Background: There is a limited understanding of molecular and cellular events that derive disease progression in patients with corona virus disease 2019 (COVID-19). Receptor for advanced glycation end products (RAGE) is hyperactive in development and complications of several diseases by mediating oxidative stress and inflammation in the body. The present study aims to explore activation of RAGE signaling in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with preexisting comorbidities, including hypertension and or diabetes. Methods: A total of 442 subjects with COVID-19, were recruited for the study. The molecular mechanism of Covid-19 was explored in blood cells, using ELISA, RT- PCR and Western blot. Results: Enhanced levels of ligands of RAGE, including AGEs, S100, and high-mobility group box-1 (HMGB-1) were observed in COVID-19 patients with severe diseases; however, their level was significantly higher in COVID-19 patients with comorbidities compared to COVID-19 patients without comorbidities. The expression of RAGE in parallel to ligands accumulation was significantly increased in patients with severe disease and comorbidities compared to COVID-19 patients with severe disease without comorbidities. The expression of downstream effectors of RAGE, including STAT-3 and nuclear factor kappa B (NF-kB), was also enhanced and their activity was increased in COVID-19 patients with comorbidities. Levels of inflammatory and oxidative stress biomarkers were markedly increased in COVID-19 patients with comorbidities. Conclusions: We conclude that upregulated RAGE axis plays critical role, to worsen the severity of the SARS-CoV-2 infection in patients with preexisting comorbidities and partly explain inflammatory and oxidative stress storm in severe COVID-19 patients.

Glycation-Driven Inflammation: COVID-19 Severity in Pregnant Women and Perinatal Outcomes.

The link between being pregnant and overweight or obese and the infectivity and virulence of the SARS CoV-2 virus is likely to be caused by SARS-CoV-2 spike protein glycosylation, which may work as a glycan shield. Methylglyoxal (MGO), an important advanced glycation end-product (AGE), and glycated albumin (GA) are the results of poor subclinical glucose metabolism and are indices of oxidative stress. Forty-one consecutive cases of SARS-CoV-2-positive pregnant patients comprising 25% pre-pregnancy overweight women and 25% obese women were recruited. The aim of our study was to compare the blood levels of MGO and GA in pregnant women with asymptomatic and symptomatic SARS-CoV-2 infection with pregnant women without SARS-CoV-2 infection with low risk and uneventful pregnancies and to evaluate the relative perinatal outcomes. The MGO and GA values of the SARS-CoV-2 cases were statistically significantly higher than those of the negative control subjects. In addition, the SARS-CoV-2-positive pregnant patients who suffered of moderate to severe COVID-19 syndrome had higher values of GA than those infected and presenting with mild symptoms or those with asymptomatic infection. Premature delivery and infants of a small size for their gestational age were overrepresented in this cohort, even in mild-asymptomatic patients for whom delivery was not indicated by the COVID-19 syndrome. Moreover, ethnic minorities were overrepresented among the severe cases. The AGE-RAGE oxidative stress axis on the placenta and multiple organs caused by MGO and GA levels, associated with the biological mechanisms of the glycation of the SARS-CoV-2 spike protein, could help to explain the infectivity and virulence of this virus in pregnant patients affected by being overweight or obese or having gestational diabetes, and the increased risk of premature delivery and/or low newborn weight.

Advanced Glycation End Products (AGEs) and Chronic Kidney Disease: Does the Modern Diet AGE the Kidney?

Since the 1980s, chronic kidney disease (CKD) affecting all ages has increased by almost 25%. This increase may be partially attributable to lifestyle changes and increased global consumption of a "western" diet, which is typically energy dense, low in fruits and vegetables, and high in animal protein and ultra-processed foods. These modern food trends have led to an increase in the consumption of advanced glycation end products (AGEs) in conjunction with increased metabolic dysfunction, obesity and diabetes, which facilitates production of endogenous AGEs within the body. When in excess, AGEs can be pathological via both receptor-mediated and non-receptor-mediated pathways. The kidney, as a major site for AGE clearance, is particularly vulnerable to AGE-mediated damage and increases in circulating AGEs align with risk of CKD and all-cause mortality. Furthermore, individuals with significant loss of renal function show increased AGE burden, particularly with uraemia, and there is some evidence that AGE lowering via diet or pharmacological inhibition may be beneficial for CKD. This review discusses the pathways that drive AGE formation and regulation within the body. This includes AGE receptor interactions and pathways of AGE-mediated pathology with a focus on the contribution of diet on endogenous AGE production and dietary AGE consumption to these processes. We then analyse the contribution of AGEs to kidney disease, the evidence for dietary AGEs and endogenously produced AGEs in driving pathogenesis in diabetic and non-diabetic kidney disease and the potential for AGE targeted therapies in kidney disease.

RAGE against the Machine: Can Increasing Our Understanding of RAGE Help Us to Battle SARS-CoV-2 Infection in Pregnancy?

The receptor of advanced glycation end products (RAGE) is a receptor that is thought to be a key driver of inflammation in pregnancy, SARS-CoV-2, and also in the comorbidities that are known to aggravate these afflictions. In addition to this, vulnerable populations are particularly susceptible to the negative health outcomes when these afflictions are experienced in concert. RAGE binds a number of ligands produced by tissue damage and cellular stress, and its activation triggers the proinflammatory transcription factor Nuclear Factor Kappa B (NF-κB), with the subsequent generation of key proinflammatory cytokines. While this is important for fetal membrane weakening, RAGE is also activated at the end of pregnancy in the uterus, placenta, and cervix. The comorbidities of hypertension, cardiovascular disease, diabetes, and obesity are known to lead to poor pregnancy outcomes, and particularly in populations such as Native Hawaiians and Pacific Islanders. They have also been linked to RAGE activation when individuals are infected with SARS-CoV-2. Therefore, we propose that increasing our understanding of this receptor system will help us to understand how these various afflictions converge, how forms of RAGE could be used as a biomarker, and if its manipulation could be used to develop future therapeutic targets to help those at risk.

SARS-CoV-2 Causes Lung Inflammation through Metabolic Reprogramming and RAGE.

Clinical studies indicate that patients infected with SARS-CoV-2 develop hyperinflammation, which correlates with increased mortality. The SARS-CoV-2/COVID-19-dependent inflammation is thought to occur via increased cytokine production and hyperactivity of RAGE in several cell types, a phenomenon observed for other disorders and diseases. Metabolic reprogramming has been shown to contribute to inflammation and is considered a hallmark of cancer, neurodegenerative diseases, and viral infections. Malfunctioning glycolysis, which normally aims to convert glucose into pyruvate, leads to the accumulation of advanced glycation end products (AGEs). Being aberrantly generated, AGEs then bind to their receptor, RAGE, and activate several pro-inflammatory genes, such as IL-1b and IL-6, thus, increasing hypoxia and inducing senescence. Using the lung epithelial cell (BEAS-2B) line, we demonstrated that SARS-CoV-2 proteins reprogram the cellular metabolism and increase pyruvate kinase muscle isoform 2 (PKM2). This deregulation promotes the accumulation of AGEs and senescence induction. We showed the ability of the PKM2 stabilizer, Tepp-46, to reverse the observed glycolysis changes/alterations and restore this essential metabolic process.

The Role of Emirati Women in Confronting Social Media Misconceptions on the Covid Vaccine

As disagreements rage about the source of the Covid-19 virus, one universal consensus has been established. It is that humanitys surest guarantee to curbing and mitigating the deadly pandemic is the discovery and wide administration of a vaccine to prevent infection, serious illnesses, and hospitalizations etc. As different countries grapple to roll out the covid vaccine, the world is confronted by another virus that could prove to undermine efforts at curbing Covid-19. Vaccine misinformation is playing into the hands of anti-vaccine groups who are taking advantage of social media platforms that are easily accessible and devoid of editorial gatekeeping to propagate often unfounded rumors about vaccine efficacy and safety. As a result, today, vaccine hesitancy is undermining the efforts put in place to fight the virus. Despite this, today the UAE is among the top three countries in the world with the highest vaccinated population. This paper attempts to provide insight into the uptake of Covid vaccine among Emirati women. The paper assumes that the decision to take covid vaccine or not is, among others, a product of information and perception. Given the centrality of social media as a source of information to most people in the UAE, we inquire into its role in shaping perceptions and attitudes on the covid vaccine among Emirati women. Our findings reveal that over 84% of respondents are vaccinated and factors that account for such vaccine uptake among Emirati women are both general and specific and center around communication and government policy. The paper concludes that contrary to established stereotypical images of Middle Eastern, Arab, Muslim women as passive and laid back, the attitude of Emirati women towards the vaccine brings to fore the role of women in social change thereby challenging established stereotypes.

Advanced Glycation End-Products (AGEs): Formation, Chemistry, Classification, Receptors, and Diseases Related to AGEs.

Advanced glycation end-products (AGEs) constitute a non-homogenous, chemically diverse group of compounds formed either exogeneously or endogeneously on the course of various pathways in the human body. In general, they are formed non-enzymatically by condensation between carbonyl groups of reducing sugars and free amine groups of nucleic acids, proteins, or lipids, followed by further rearrangements yielding stable, irreversible end-products. In the last decades, AGEs have aroused the interest of the scientific community due to the increasing evidence of their involvement in many pathophysiological processes and diseases, such as diabetes, cancer, cardiovascular, neurodegenerative diseases, and even infection with the SARS-CoV-2 virus. They are recognized by several cellular receptors and trigger many signaling pathways related to inflammation and oxidative stress. Despite many experimental research outcomes published recently, the complexity of their engagement in human physiology and pathophysiological states requires further elucidation. This review focuses on the receptors of AGEs, especially on the structural aspects of receptor-ligand interaction, and the diseases in which AGEs are involved. It also aims to present AGE classification in subgroups and to describe the basic processes leading to both exogeneous and endogeneous AGE formation.

RAGE/Diaph1, Diabetes, and Kidney Disease: Mechanisms and Novel Therapeutic Strategies

In Year Three of the funded grant, we have substantial progress in the following critical areas: 1). As noted in the project narrative, we generated four different lines of mice to directly test the hypothesis that RAGE and DIAPH1 contribute to the pathogenesis of diabetes-associated nephropathy in the podocytes and/or in myeloid cells/macrophages. All of the mouse lines are now generated and largely completed (mice sacrificed) and samples being evaluation by Dr DAgati. There are no new pending mice to generate all are generated and on time course. 2). We have determined that the small molecule RAGE/DIAPH1 antagonist is best administered orally and that the RAGE antagonist survives the medicated chow pelleting, heating and irradiation. Our first data on treated vs. untreated male and female diabetic mice illustrates reduction in mesangial sclerosis, reduced thickening of the glomerular basement membrane and reduction in podocyte effacement in diabetic mice receiving RAGE229 medicated chow (vs vehicle). Additional mice are on study and time course at this time to complete the indicated enrollment.3). For transcriptomics and metabolomics/lipidomics assay, Dr. Ramasamy will be testing the macrophages from the mice through the time course and he has verified all of his experimental systems for the performance of the outlined studies. Dr. Ramasamy identifies substantial progress in the development and validation of metabolomics and lipidomics assays here at NYU and in transcriptomic data (all on macrophages) in order to understand detailed mechanisms of the role of these molecules in the diabetic kidney. Taken together, despite the >3 month shutdown due to COVID19 our work in Year 3 has been productive and we await tissue and other analyses, as above, to render final conclusions.

CONTRIBUTING FACTORS TO THE VIOLENT BEHAVIOUR IN VARIOUS SOCIAL CONTEXTS

In the first part of this article, we present an analysis of the concept of violent behaviour in various social contexts and in the international sociological literature. In the second part, we approach the concrete factors that favor the manifestation of violence in different conjunctures, in Romania and in the world, as there is the problem of consequences determined by the widespread mentality of acceptance / tolerance of the domination of masculinity in social life, but also the problem of excessive popularization of the violence subculture through the media. The perspective of the increased incidence of social violence is also addressed as an effect of the chronic phenomenon of poverty in certain types of families. The data and information used come from international and national sources as WHO, UN or NIS Bucharest, but also from the scientific results of the authors who belong to the Research Institute for Quality of Life, Romanian Academy, Bucharest.

Behavioural consequences of verbally expressed and unexpressed customer rage emotions

Purpose: The purpose of this study is to distinguish those emotions which customers express verbally during a failed remote service encounter from those which they do not. The study further attempts to investigate the post-consumption customer behaviour of verbally expressed and unexpressed negative customer emotions. Design/methodology/approach: The authors used a survey-based research design. The hypotheses were tested through the “partial least squared structural equation modelling” method. Findings: This study shows that in a failed remote service encounter, customers verbally express retaliatory rage emotions, such as anger and rage. At the same time, they are able to suppress rancorous rage emotions, such as disgust and contempt and do not express them verbally. The authors demonstrate that after emotions are verbally expressed during a failed remote service encounter, they are followed by the post-consumption behaviours of negative word of mouth and revenge;when emotions are not expressed verbally during a failed service encounter, they are followed up by exit behaviour. Research limitations/implications: The effects of variables, such as switching costs and individual and situational factors, can be investigated in the model. Future studies can also explore the role of organizational interventions, such as explanation and apology, on negative customer emotions during failed remote service encounters. Their moderating impact on customer behaviour during and after the encounters can be investigated. Practical implications: This study has much practical relevance in the post-COVID-19 world, where remote service delivery is becoming the new normal in many sectors. In remote service delivery situations, verbally unexpressed negative emotions can remain undetected;however, they have negative consequences for firms. This study underscores the need to train frontline employees to notice these unexpressed emotions so that service recoveries can be initiated. Originality/value: This paper contributes to the area of dysfunctional customer behaviour and service recovery. The existing literature has not explored whether some negative emotions are expressed during a failed service encounter and then acted upon later, and some emotions are not expressed but acted upon later. This study addresses the problem of firms getting caught unawares when they find customers resorting to undesirable post-consumption behaviour without demonstrating any verbal expressions during the preceding failed service encounters. © 2022, Emerald Publishing Limited.

Oxidative stress and inflammatory markers in patients with COVID-19: Potential role of RAGE, HMGB1, GFAP and COX-2 in disease severity.

BACKGROUND: SARS-CoV-2 infection can lead to the abnormal induction of cytokines and a dysregulated hyperinflammatory state that is implicated in disease severity and risk of death. There are several molecules present in blood associated with immune cellular response, inflammation, and oxidative stress that could be used as severity markers in respiratory viral infections such as COVID-19. However, there is a lack of clinical studies evaluating the role of oxidative stress-related molecules including glial fibrillary acidic protein (GFAP), the receptor for advanced glycation end products (RAGE), high mobility group box-1 protein (HMGB1) and cyclo-oxygenase-2 (COX-2) in COVID-19 pathogenesis. AIM: To evaluate the role of oxidative stress-related molecules in COVID-19. METHOD: An observational study with 93 Brazilian participants from September 2020 to April 2021, comprising 23 patients with COVID-19 admitted to intensive care unit (ICU), 19 outpatients with COVID-19 with mild to moderate symptoms, 17 individuals reporting a COVID-19 history, and 34 healthy controls. Blood samples were taken from all participants and western blot assay was used to determine the RAGE, HMGB1, GFAP, and COX-2 immunocontent. RESULTS: We found that GFAP levels were higher in patients with severe or critical COVID-19 compared to outpatients (p = 0.030) and controls (p < 0.001). A significant increase in immunocontents of RAGE (p < 0.001) and HMGB1 (p < 0.001) were also found among patients admitted to the ICU compared to healthy controls, as well as an overexpression of the inducible COX-2 (p < 0.001). In addition, we found a moderate to strong correlation between RAGE, GFAP and HMGB1 proteins. CONCLUSION: SARS-CoV-2 infection induces the upregulation of GFAP, RAGE, HMGB1, and COX-2 in patients with the most severe forms of COVID-19.