Common Mechanism Research Articles

Chronic organ damage: Understanding fibrosis

Chronic organ damage: Understanding fibrosis Fibrosis was once considered irreversible, resulting from chronic organ damage; Ken-Ichi Kobayashi from Notre Dame Seishin University tells us why the possibility of treatment to reverse the disease is gaining attention. Organ fibrosis is a common phenomenon observed in various organ failure states resulting from disease and aging. The most common examples are renal fibrosis in chronic kidney disease, liver fibrosis in cirrhosis, lung fibrosis in idiopathic pulmonary fibrosis, and pancreatic fibrosis in chronic pancreatitis. The total number of patients with organ fibrosis in Japan is nearly 20 million, and it is no exaggeration to say that it is a ‘national disease.’ Until recently, fibrosis was considered to be the end result of chronic organ damage and an irreversible condition with a poor prognosis. In recent years, however, fibrosis has begun to be recognized as a reversible process, and the possibility of treatment is gaining attention. It is also becoming clear that fibrosis is caused by complex cellular and inter-organic networks rather than by specific organs, and therefore, common pathological mechanisms are thought to exist even in various types of fibrosis. However, the common pathological mechanism of fibrosis, especially fibrosis-attracting factors, is still an enigma.

Kitesurfing and snowkiting injuries in Norway: a retrospective study

BackgroundKiteboarding (kitesurfing on water and snowkiting) is a fairly new sport and is defined as a high-risk sport. The injury rate has been reported to be between 6 and 9 per 1000 h. The aim of the study was to identify and describe kiteboarding-related injuries in Norway over a five-year period.MethodsWe used “snowball sampling” to identify kiteboarding accidents in a retrospective study. In addition, we conducted structural searches in the National Air Ambulance Service and Search and Rescue Helicopter patient record databases. All included informants were interviewed. Descriptive methods were used to characterise the sample.ResultsTwenty-nine kiteboarders were included, with a total of 33 injuries. One half of the injuries to head, face and neck were cerebral concussions (n = 12). The most common type of injury was bone fractures (n = 28), followed by soft tissue injuries (n = 24). Most injuries were of moderate severity (51%) and falling from less than 5 m was the most common mechanism of injury. Operator error and lack of experience were the most frequently reported causes of accidents (82%).ConclusionsSerious injuries occured during kiteboarding. The majority of kiteboarders reported operator error or lack of experience as the cause of their accident. Prior to kiteboarding, a course highlighting the importance in using helmet for snowkiting and both helmet and life vest in kitesurfing, should be mandatory.

1850 Dogs and Bones

Abstract Introduction The health benefits of owning dogs include improved physical activity, mental well-being, companionship, and so forth. However, musculoskeletal injuries caused by dog-related activities might negate the aforementioned benefits. The aim of this study was to estimate the number of femoral fractures directly linked to dog-related activities in people above the age of 60. Methods In this observational study, we included all patients above the age of 60 with femoral fractures caused by dog-related activities, over a one-year period (June 2022 to May 2023). We chose to include people above the age of 60 because they are more likely to have a fragility fracture and are entered in the National Hip Fracture Database. Results 387 patients (above the age of 60) were admitted with femoral fractures during the study period. Of these, 16 were directly related to dog-related activities. The common mechanisms of injuries include being tripped, pulled down and jumped over by a dog, and tangled and tripped by the dog leash. Conclusion 4% of femoral fractures (1 in 25) in people above the age of 60 were caused by dog-related activities. This is probably an underestimate, because some owners may not have volunteered this information out of love for their dogs and inadequate history regarding the circumstances that led to the fall. Despite the injuries, all patients still loved their dogs and wanted to go home as soon as possible to be with them. There were more fractures in spring and summer (11) compared to autumn and winter (5) which reflects increased activity with better weather. Having a dog is a risk factor for falls and fractures. We recommend that dog owners carefully consider their choice of dogs and if there are issues with handling them, both dogs and their owners should receive appropriate training.

Psychological Impact of a Prenatal Diagnosis of Congenital Heart Disease on Parents: Is It Time for Tailored Psychological Support?

The prenatal diagnosis of congenital heart disease (CHD) represents, for both parents, a particularly stressful and traumatic life event from a psychological point of view. The present review sought to summarize the findings of the most relevant literature on the psychological impact of prenatal diagnosis of CHD on parents, describing the most common mechanisms employed in order to face this unexpected finding. We also highlight the importance of counseling and the current gaps in the effects of psychological support on this population.

Relationship between osteoporosis and joint pathologies. New approach to treatment of arthritis and osteoarthritis

The article discusses the common pathogenetic mechanisms of the development of osteoporosis and joint diseases. The concept of doctor of medical sciences (habil.), professor V.I. Strukov is presented about the influence of osteoporotic bone cavities on the development of degenerative processes in cartilage tissue. A new approach to the treatment of diseases of the musculoskeletal system using drugs of gonadotropic and osteoimmunological action of the Osteomed group is presented.

Enhancing sexual health in primary care: Guidance for practitioners.

Sexual health is an integral aspect of overall health and well-being and is fundamental to the sustainable development of societies worldwide. The World Health Organization (WHO) defines sexual health as 'a state of physical, emotional, mental, and social well-being in relation to sexuality'. However, addressing sexual health has been afforded low priority in primary healthcare systems. Primary care practitioners (PCPs), who play a crucial role in providing comprehensive care to communities, receive little training on screening and managing individuals with sexual health problems. The scope of services ranges from education, prevention and screening, to management of sexual health matters. Patients with noncommunicable diseases (NCDs), such as stroke, cancer, heart disease and diabetes, are at increased risk for sexual dysfunction, possibly because of common pathogenetic mechanisms, such as inflammation. This is of considerable importance in the sub-Saharan African context where there is a rapidly increasing prevalence of NCDs, as well as a high burden of HIV. Strategies to improve the quality of sexual health services in primary care include creating a safe and non-judgemental practice environment for history-taking among gender-diverse populations, utilising effective screening tools aligned with the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for sexual dysfunctions. In particular, the International Consultation on Sexual Medicine (ICSM -5) diagnostic and treatment algorithm can empower primary care providers to effectively address sexual dysfunctions among patients and improve the quality of care provided to communities regarding sexual and reproductive health.

Identification of Co-diagnostic Genes for Heart Failure and Hepatocellular Carcinoma Through WGCNA and Machine Learning Algorithms.

This research delves into the intricate relationship between hepatocellular carcinoma (HCC) and heart failure (HF) by exploring shared genetic characteristics and molecular processes. Employing advanced methodologies such as differential analysis, weighted correlation network analysis (WGCNA), and algorithms like Random Forest (RF), Least Absolute Shrinkage Selection (LASSO), and XGBoost, we meticulously identified modular differential genes (DEGs) associated with both HF and HCC. Gene Set Variation Analysis (GSVA) and single sample gene set enrichment analysis (ssGSEA) were employed to unveil underlying biological mechanisms. The study revealed 88 core genes shared between HF and HCC, indicating a common mechanism. Enrichment analysis emphasized the roles of immune responses and inflammation in both diseases. Leveraging XGBoost, we crafted a robust multigene diagnostic model (including FCN3, MAP2K1, AP3M2, CDH19) with an area under the curve (AUC)>0.9, showcasing exceptional predictive accuracy. GSVA and ssGSEA analyses unveiled the involvement of immune cells and metabolic pathways in the pathogenesis of HF and HCC. This research uncovers a pivotal interplay between HF and HCC, highlighting shared pathways and key genes, offering promising insights for future clinical treatments and experimental research endeavors.

Total Number of Rtas that were Brought to the Gujranwala Teaching Hospital's Trauma Center, along with their Results

Background: Trauma, particularly arising from road traffic accidents (RTAs), is a significant public health issue worldwide, with a notably high incidence in Pakistan. The vulnerability to traumatic injuries is exacerbated by socio-economic, environmental, and infrastructural factors. Young males are disproportionately affected, reflecting societal roles and risk behaviors. The efficiency of trauma care, influenced by the location and resources of trauma centers, plays a crucial role in patient outcomes. Objective: This study aims to assess the patterns, causes, and outcomes of trauma cases treated at the Gujranwala Teaching Hospital (GTH) trauma center, with a focus on identifying demographic trends, predominant injury mechanisms, and the effectiveness of trauma care facilities. Methods: An institution-based cross-sectional study was conducted from November 2021 to February 2022 at the GTH trauma center. Ethical approval was obtained from the Department of Emergency Medicine Ethics Committee at GMC Teaching Hospital. Data were collected using a WHO-guided pre-tested form, documenting sociodemographic profiles, clinical profiles, injury mechanisms, and outcomes. The study involved 813 trauma patients, with data analysis performed using SPSS version 25. Descriptive and inferential statistics were employed to analyze patient demographics, injury patterns, and outcomes. Results: The study comprised 813 patients, predominantly male (75.3%). The median age was 33 years, ranging from 1.5 to 85 years. RTAs were the most common injury mechanism (78.6%), primarily affecting passengers (70.9%) and pedestrians (29.1%). Head injuries were the most frequent anatomical site of injury (45.75%). The triage categories showed 73.76% of patients in the 'Yellow' category. The overall mortality prevalence was 3.6%. Conclusion: The study highlights the high prevalence of RTAs as a cause of trauma, particularly among young males. The findings underscore the need for improved trauma care facilities, stricter enforcement of traffic safety laws, and public awareness campaigns on road safety. Establishing well-equipped trauma centers near highways and enhancing prehospital care could significantly reduce trauma-related fatalities.

Mechanisms of shoulder trauma: Current concepts.

Acute traumatic injuries to the glenohumeral articulation are common. The types of injuries depend on age, muscle strength, bone density, and biomechanics of the traumatic event. Understanding the different mechanisms of trauma and how they affect the functional anatomical structures of the shoulder joint is crucial for the treatment of these lesions. Therefore, when clinicians have knowledge of these mechanisms they can accurately diagnose and treat shoulder pathology and predict distinct injury patterns. Here, we have described the fundamentals of the mechanisms of injury of the glenohumeral dislocation, dislocation with fracture of the humeral head, and the proximal humerus fracture. We have focused on common injury mechanisms and the correlation with radiological diagnostics. Radiological and laboratory findings of distinct types of injury were also discussed.

SOS2 modulates the threshold of EGFR signaling to regulate osimertinib efficacy and resistance in lung adenocarcinoma.

Son of sevenless 1 and 2 (SOS1 and SOS2) are RAS guanine nucleotide exchange factors (RasGEFs) that mediate physiologic and pathologic receptor tyrosine kinase (RTK)-dependent RAS activation. Here, we show that SOS2 modulates the threshold of epidermal growth factor receptor (EGFR) signaling to regulate the efficacy of and resistance to the EGFR tyrosine kinase inhibitor (EGFR-TKI) osimertinib in lung adenocarcinoma (LUAD). SOS2 deletion (SOS2KO ) sensitized EGFR-mutated cells to perturbations in EGFR signaling caused by reduced serum and/or osimertinib treatment to inhibit phosphatidylinositol 3-kinase (PI3K)/AKT pathway activation, oncogenic transformation, and survival. Bypassing RTK reactivation of PI3K/AKT signaling represents a common resistance mechanism to EGFR-TKIs; SOS2KO reduced PI3K/AKT reactivation to limit osimertinib resistance. In a forced HGF/MET-driven bypass model, SOS2KO inhibited hepatocyte growth factor (HGF)-stimulated PI3K signaling to block HGF-driven osimertinib resistance. Using a long-term in situ resistance assay, most osimertinib-resistant cultures exhibited a hybrid epithelial/mesenchymal phenotype associated with reactivated RTK/AKT signaling. In contrast, RTK/AKT-dependent osimertinib resistance was markedly reduced by SOS2 deletion; the few SOS2KO cultures that became osimertinib resistant primarily underwent non-RTK-dependent epithelial-mesenchymal transition (EMT). Since bypassing RTK reactivation and/or tertiary EGFR mutations represent most osimertinib-resistant cancers, these data suggest that targeting proximal RTK signaling, here exemplified by SOS2 deletion, has the potential to delay the development osimertinib resistance and enhance overall clinical responses for patients with EGFR-mutated LUAD.

Psoriasis, bone and bowel: a comprehensive review and new insights

Psoriasis is a chronic immune-mediated disorder affecting about 2% of the population worldwide which is associated with significant morbidity. The disease usually presents as raised, well-demarcated erythematous plaques with adherent silvery scales. Psoriasis can appear at any age but it has two peaks occurring at 15–20 and 55–60 years of age. It affects males and females equally. Despite the multitude of investigations about psoriasis and even development of drugs with satisfactory results, its pathogenesis is not fully understood yet and its course is unpredictable. Various environmental triggers, e.g., obesity, stress and drugs may induce disease in genetically susceptible patients. Although psoriasis was considered primarily as a disease of the skin, more investigations have been revealed its systemic nature. Psoriatic arthritis (PsA) may complicate up to one-third of cases of psoriasis vulgaris (PV). Also, the association between psoriasis and a variety of other immune-mediated disorders such as inflammatory bowel disease (IBD) and celiac disease (CD) has been confirmed in various studies. Moreover, a growing body of evidences indicates that psoriasis shares some common histological and phenotypical properties with the spectrum of osteoimmunological diseases such as Paget’s disease of bone (PDB). Thus, exploring the common molecular and genetic mechanisms underlying psoriasis and related disorders is of paramount importance for better elucidating disease pathogenesis and designing more targeted treatments.

Autophagy Markers Are Altered in Alzheimer's Disease, Dementia with Lewy Bodies and Frontotemporal Dementia.

The accumulation of protein aggregates defines distinct, yet overlapping pathologies such as Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). In this study, we investigated ATG5, UBQLN2, ULK1, and LC3 concentrations in 66 brain specimens and 120 plasma samples from AD, DLB, FTD, and control subjects (CTRL). Protein concentration was measured with ELISA kits in temporal, frontal, and occipital cortex specimens of 32 AD, 10 DLB, 10 FTD, and 14 CTRL, and in plasma samples of 30 AD, 30 DLB, 30 FTD, and 30 CTRL. We found alterations in ATG5, UBQLN2, ULK1, and LC3 levels in patients; ATG5 and UBQLN2 levels were decreased in both brain specimens and plasma samples of patients compared to those of the CTRL, while LC3 levels were increased in the frontal cortex of DLB and FTD patients. In this study, we demonstrate alterations in different steps related to ATG5, UBQLN2, and LC3 autophagy pathways in DLB and FTD patients. Molecular alterations in the autophagic processes could play a role in a shared pathway involved in the pathogenesis of neurodegeneration, supporting the hypothesis of a common molecular mechanism underlying major neurodegenerative dementias and suggesting different potential therapeutic targets in the autophagy pathway for these disorders.

Cooperation and Competition of RNA Secondary Structure and RNA-Protein Interactions in the Regulation of Alternative Splicing.

The regulation of alternative splicing in eukaryotic cells is carried out through the coordinated action of a large number of factors, including RNA-binding proteins and RNA structure. The RNA structure influences alternative splicing by blocking cis-regulatory elements, or bringing them closer or farther apart. In combination with RNA-binding proteins, it generates transcript conformations that help to achieve the necessary splicing outcome. However, the binding of regulatory proteins depends on RNA structure and, vice versa, the formation of RNA structure depends on the interaction with regulators. Therefore, RNA structure and RNA-binding proteins are inseparable components of common regulatory mechanisms. This review highlights examples of alternative splicing regulation by RNA-binding proteins, the regulation through local and long-range RNA structures, as well as how these elements work together, cooperate, and compete.

Deferoxamine protects cochlear hair cells and hair cell-like HEI-OC1 cells against tert-butyl hydroperoxide-induced ototoxicity

Oxidative stress is the common mechanism of sensorineural hearing loss (SNHL) caused by many factors, such as noise, drugs and ageing. Here, we used tert-butyl hydroperoxide (t-BHP) to cause oxidative stress damage in HEI-OC1 cells and in an in vitro cochlear explant model. We observed lipid peroxidation, iron accumulation, mitochondrial shrinkage and vanishing of mitochondrial cristae, which caused hair cell ferroptosis, after t-BHP exposure. Moreover, the number of TUNEL-positive cells in cochlear explants and HEI-OC1 cells increased significantly, suggesting that t-BHP caused the apoptosis of hair cells. Administration of deferoxamine (DFOM) significantly attenuated t-BHP-induced hair cell loss and disordered hair cell arrangement in cochlear explants as well as HEI-OC1 cell death, including via apoptosis and ferroptosis. Mechanistically, we found that DFOM treatment reduced t-BHP-induced lipid peroxidation, iron accumulation and mitochondrial pathological changes in hair cells, consequently mitigating apoptosis and ferroptosis. Moreover, DFOM treatment alleviated GSH depletion caused by t-BHP and activated the Nrf2 signalling pathway to exert a protective effect. Furthermore, we confirmed that the protective effect of DFOM mainly depended on its ability to chelate iron by constructing Fth1 knockout (KO), TfR1 KO and Nrf2 KO HEI-OC1 cell lines using CRISPR/Cas9 technology and a Flag-Fth1 (overexpression) HEI-OC1 cell line using the FlpIn™ System. Our findings suggest that DFOM is a potential drug for SNHL treatment due to its ability to inhibit apoptosis and ferroptosis by chelating iron and scavenging reactive oxygen species (ROS).

Proteomic analysis of the mucus of the photosynthetic sea slug Elysia crispata

Elysia crispata is a tropical sea slug that can retain intracellular functional chloroplasts from its algae prey, a mechanism termed kleptoplasty. This sea slug, like other gastropods, secretes mucus, a viscous secretion with multiple functions, including lubrication, protection, and locomotion. This study presents the first comprehensive analysis of the mucus proteome of the sea slug E. crispata using gel electrophoresis and HPLC-MS/MS. We identified 306 proteins in the mucus secretions of this animal, despite the limited entries for E. crispata in the Uniprot database. The functional annotation of the mucus proteome using Gene Ontology identified proteins involved in different functions such as hydrolase activity (molecular function), carbohydrate-derived metabolic processes (biological processes) and cytoskeletal organization (cell component). Moreover, a high proportion of proteins with enzymatic activity in the mucus of E. crispata suggests potential biotechnological applications including antimicrobial and antitumor activities. Putative antimicrobial properties are reinforced by the high abundance of hydrolases. This study also identified proteins common in mucus samples from various species, supporting a common mechanism of mucus in protecting cells and tissues while facilitating animal movement. SignificanceMarine species are increasingly drawing the interest of researchers for their role in discovering new bioactive compounds. The study “Proteomic Analysis of the Mucus of the Photosynthetic Sea Slug Elysia crispata” is a pioneering effort that uncovers the complex protein content in this fascinating sea slug's mucus.This detailed proteomic study has revealed proteins with potential use in biotechnology, particularly for antimicrobial and antitumor purposes. This research is a first step in exploring the possibilities within the mucus of Elysia crispata, suggesting the potential for new drug discoveries. These findings could be crucial in developing treatments for severe diseases, especially those caused by multidrug-resistant bacteria, and may lead to significant advances in medical research.

Abstract B094: The role of paraspeckles and splicing regulation in driving basal-like pancreatic cancer

Abstract The basal-like pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive type of mesenchymal PDAC that resists treatment and has a poor prognosis. Understanding the mechanisms driving basal-like PDAC biology will be essential for development of treatment strategies for this aggressive tumor. We have previously shown that loss of the tumor-suppressive non-coding RNA Neat1 recapitulate the phenotype of Arid1a-deficient mice (a component of the SWI/SNF chromatin remodeling complex) in a mouse model for PDAC, with loss of exocrine pancreatic identity and development of acinar- and ductal-derived lesions (Mello et al., 2017), suggesting that Neat1 and Arid1a may share a common molecular mechanism. We now demonstrate that the loss of these two divergent genes induce the emergence of basal-like PDAC. This provides an opportunity to probe for shared features specific to Neat1- and Arid1a-deficient PDAC, as compared to PDAC in which both genes are functional. Notably, our data indicate that both Neat1- and Arid1a-deficient pancreatic cells fail to form nuclear paraspeckles, i.e. structures implicated in the retention of RNA splicing factors. Consistent with this idea, we also find significantly increased exon-skipping, including a sub-set of such events shared between Neat1- and Arid1a-deficient PDAC. In addition, nucleotide sequence motifs associated with exon-skipping locations suggest involvement of RNA splicing factors known to accumulate in paraspeckles, such as Srsf1, Srsf2, Srsf10, Rbm38, Dazap1 and others. We also show that, upon genetic or pharmacological attenuation of splicing regulator function, basal-like PDAC develop epithelial features, reminiscent of mesenchymal-epithelial transition, reduce both their proliferation and migration potential and undergo cell death. Our findings provide an important opportunity to elucidate the molecular pathways that link aberrant RNA splicing and paraspeckle deficiency to basal-like PDAC, providing new insight for the development of mechanism-based novel PDAC treatment strategies to improve patient outcome. Citation Format: Zamira G. Soares, Emily Berry, Dakarai Esgdaille, Jennifer Twardowski, Stephano S. Mello. The role of paraspeckles and splicing regulation in driving basal-like pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B094.

Exploring DNA Damage and Repair Mechanisms: A Review with Computational Insights.

DNA damage is a critical factor contributing to genetic alterations, directly affecting human health, including developing diseases such as cancer and age-related disorders. DNA repair mechanisms play a pivotal role in safeguarding genetic integrity and preventing the onset of these ailments. Over the past decade, substantial progress and pivotal discoveries have been achieved in DNA damage and repair. This comprehensive review paper consolidates research efforts, focusing on DNA repair mechanisms, computational research methods, and associated databases. Our work is a valuable resource for scientists and researchers engaged in computational DNA research, offering the latest insights into DNA-related proteins, diseases, and cutting-edge methodologies. The review addresses key questions, including the major types of DNA damage, common DNA repair mechanisms, the availability of reliable databases for DNA damage and associated diseases, and the predominant computational research methods for enzymes involved in DNA damage and repair.

Chemical Proteomics and Morphological Profiling Revealing MYDGF as a Target for Synthetic Anticancer Macromolecules.

Biodegradable guanidinium-functionalized polycarbonates kill cancer cells via membrane translocation without causing resistance after repeated use, but the exact molecular targets of the polycarbonates are unknown. Here, we investigate the protein targets of the polycarbonates through affinity-based protein profiling and report myeloid-derived growth factor (MYDGF) as the main protein target. Direct binding of the polycarbonates to MYDGF protein is validated through biolayer interferometry. MYDGF is overexpressed in a range of cancer cells, and knockdown of MYDGF is shown to reduce cell proliferation in cancer cells. Through morphological profiling, we also identify similarities in phenotypic effects of the functionalized polycarbonates with topoisomerase I inhibitors, MDM2 inhibitors, and phosphatidylinositol 3kinase inhibitors against cancer cells, suggesting a common mechanism through the PIK3/AKT pathway leading to apoptosis. These findings present the first macromolecular compound targeting MYDGF and may serve as an example for MYDGF modulation as a potential new target for macromolecular chemotherapeutic development.

The Role of microRNAs Related to Apoptosis for N-Methyl-d-Aspartic Acid-Induced Neuronal Cell Death in the Murine Retina.

Glaucoma is one of the leading causes of acquired blindness and characterized by retinal ganglion cell (RGC) death. MicroRNAs are small noncoding RNAs that degrade their target mRNAs. Apoptosis is one of the common mechanisms leading to neuronal death in many neurodegenerative diseases, including glaucoma. In the present study, we identified microRNAs that modulate RGC death caused by the intravitreal injection of N-methyl-d-aspartic acid (NMDA). We found an upregulation of miR-29b and downregulation of miR-124 in the retina of the NMDA-injected eyes. The intravitreal injection of an miR-29b inhibitor 18 h before NMDA injection reduced RGC death and the downregulation of myeloid cell leukemia 1 (MCL-1), an anti-apoptotic factor, induced by intravitreal NMDA. The intravitreal injection of an miR-124 mimic 18 h before NMDA injection also reduced RGC death and the upregulation of B-cell/chronic lymphocytic leukemia lymphoma 2 (bcl-2)-associated X protein (Bax) and bcl-2 interacting protein (Bim), pro-apoptotic factors, induced by intravitreal NMDA. These data suggest that expressional changes in microRNA are involved in the excitotoxicity of RGCs, and that complement and/or inhibition of microRNA may be a potential therapeutic approach for the diseases related to the excitotoxicity of RGCs, such as glaucoma and retinal central artery occlusion.

Albumin Redox Modifications Promote Cell Calcification Reflecting the Impact of Oxidative Status on Aortic Valve Disease and Atherosclerosis.

Calcific aortic valve disease (CAVD) and coronary artery disease (CAD) are related cardiovascular diseases in which common mechanisms lead to tissue calcification. Oxidative stress plays a key role in these diseases and there is also evidence that the redox state of serum albumin exerts a significant influence on these conditions. To further explore this issue, we used multimarker scores (OxyScore and AntioxyScore) to assess the global oxidative status in patients with CAVD, with and without CAD, also evaluating their plasma thiol levels. In addition, valvular interstitial cells were treated with reduced, oxidized, and native albumin to study how this protein and its modifications affect cell calcification. The differences we found suggest that oxidative status is distinct in CAVD and CAD, with differences in redox markers and thiol levels. Importantly, the in vitro interstitial cell model revealed that modified albumin affects cell calcification, accelerating this process. Hence, we show here the importance of the redox system in the development of CAVD, emphasizing the relevance of multimarker scores, while also offering evidence of how the redox state of albumin influences vascular calcification. These data highlight the relevance of understanding the overall redox processes involved in these diseases, opening the door to new studies on antioxidants as potential therapies for these patients.