scholarly journals Cellular exocytosis gene (EXOC6/6B): a potential molecular link for the susceptibility and mortality of COVID-19 in diabetic patients

2020 ◽  
Author(s):  
Mahmood Yaseen Hachim ◽  
Ibrahim Yaseen Hachim ◽  
Saba Al Heialy ◽  
Jalal Taneera ◽  
Nabil sulaiman
Keyword(s):  
United Arab Emirates ◽  
Molecular Mechanisms ◽  
High Rate ◽  
Diabetic Patients ◽  
Lung Epithelium ◽  
Transcriptomic Data ◽  
Insulin Granules ◽  
Increased Risk ◽  
Novel Biomarkers ◽  
Lower Expression

AbstractDiabetes is one of the most critical comorbidities linked to an increased risk of severe complications in the current coronavirus disease 2019 (COVID-19) pandemic. A better molecular understanding of COVID-19 in people with type diabetes mellitus (T2D) is mandatory, especially in countries with a high rate of T2D, such as the United Arab Emirates (UAE). Identification of the cellular and molecular mechanisms that make T2D patients prone to aggressive course of the disease can help in the discovery of novel biomarkers and therapeutic targets to improve our response to the disease pandemic. Herein, we employed a system genetics approach to explore potential genomic, transcriptomic alterations in genes specific to lung and pancreas tissues, affected by SARS-CoV-2 infection, and study their association with susceptibility to T2D in Emirati patients. Our results identified the Exocyst complex component, 6 (EXOC6/6B) gene (a component for docks insulin granules to the plasma membrane) with documented INDEL in 3 of 4 whole genome sequenced Emirati diabetic patients. Publically available transcriptomic data showed that lung infected with SARS-CoV-2 showed significantly lower expression of EXOC6/6B compared to healthy lungs.In conclusion, our data suggest that EXOC6/6B might be an important molecular link between dysfunctional pancreatic islets and ciliated lung epithelium that makes diabetic patients more susceptible to severe SARS-COV-2 complication.

scholarly journals Factors Affecting the Outcomes of Tibiotalocalcaneal Fusion

2020 ◽  
Vol 5 (4) ◽  
pp. 2473011420S0038
Author(s):  
Charles C. Pitts ◽  
Bradley Alexander ◽  
Joshua L. Washington ◽  
Hannah M. Barranco ◽  
Romil K. Patel ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Postoperative Complications ◽  
Kidney Disease ◽  
Bone Graft ◽  
Postoperative Infection ◽  
High Rate ◽  
Diabetic Patients ◽  
Charcot Arthropathy ◽  
Infection Rates ◽  
Increased Risk

Category: Hindfoot; Ankle; Ankle Arthritis Introduction/Purpose: Tibiotalocalcaneal (TTC) fusion is used to treat a variety of conditions affecting the ankle and subtalar joint, including osteoarthritis (OA), Charcot arthropathy, avascular necrosis (AVN) of the talus, failed total ankle arthroplasty, and severe deformity. The prevalence of postoperative complications remains high due to the complexity of hindfoot disease seen in these patients. The aim of this study was to analyze the relationship between preoperative conditions and postoperative complications in order to predict the outcome following primary TTC fusion. Methods: We retrospectively reviewed the medical records of 101 patients who underwent TTC fusion at the same institution between 2011 and 2019. Risk ratios (RRs) associated with age, sex, diabetes, cardiovascular disease, smoking, preoperative ankle deformity, and the use of bone graft during surgery were related to the postoperative complications. We determined from these data which pre- and perioperative factors significantly affected the outcome. Results: Patients with a preoperative diagnosis of Charcot arthropathy and non-traumatic OA had significantly higher nonunion rates of 44.4% (12 patients) and 39.1% (18 patients) (p = 0.016) and infection rates of 29.6% (eight patients) and 37% (17 patients) compared to patients with traumatic arthritis, respectively (p = 0.002). There was a significantly increased rate of nonunion in diabetic patients (RR 2.22; p = 0.010). Patients with chronic kidney disease were 2.37-times more likely to have a nonunion (p = 0.006). Patients aged over 60 years had more than a three-fold increase in the rate of postoperative infection (RR 3.60; p = 0.006). The use of bone graft appeared to be significantly protective against postoperative infection (p = 0.019). Conclusion: We were able to confirm, in the largest series of TTC ankle fusions currently in the literature, that there remains a high rate of complications following this procedure. Those with diabetes, chronic kidney disease, or aged over 60 years had an increased risk of nonunion. These findings help to confirm those of previous studies. Additionally, our study adds to the literature by showing that autologous bone graft may help in decreasing infection rates. This helps surgeons further understand which patients are at a higher risk for postoperative complications when undergoing TTC fusion. [Table: see text]

scholarly journals An Update on Molecular Pathways Regulating Vasculogenic Mimicry in Human Osteosarcoma and Their Role in Canine Oncology

2021 ◽  
Vol 8 ◽  
Author(s):  
Marcella Massimini ◽  
Mariarita Romanucci ◽  
Raffaella De Maria ◽  
Leonardo Della Salda
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Human Cancer ◽  
Vasculogenic Mimicry ◽  
Human Osteosarcoma ◽  
Increased Risk ◽  
Veterinary Pathology ◽  
Canine Tumors ◽  
Novel Biomarkers ◽  
Cancer Types

Canine tumors are valuable comparative models for human counterparts, especially to explore novel biomarkers and to understand pathways and processes involved in metastasis. Vasculogenic mimicry (VM) is a unique property of malignant cancer cells which promote metastasis. Thus, it represents an opportunity to investigate both the molecular mechanisms and the therapeutic targets of a crucial phenotypic malignant switch. Although this biological process has been largely investigated in different human cancer types, including osteosarcoma, it is still largely unknown in veterinary pathology, where it has been mainly explored in canine mammary tumors. The presence of VM in human osteosarcoma is associated with poor clinical outcome, reduced patient survival, and increased risk of metastasis and it shares the main pathways involved in other type of human tumors. This review illustrates the main findings concerning the VM process in human osteosarcoma, search for the related current knowledge in canine pathology and oncology, and potential involvement of multiple pathways in VM formation, in order to provide a basis for future investigations on VM in canine tumors.

scholarly journals TMT-Based Quantitative Proteomic Analysis Identification of Integrin Alpha 3 and Integrin Alpha 5 as Novel Biomarkers in Pathogenesis of Acute Aortic Dissection

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Lingyu Xing ◽  
Yuan Xue ◽  
Yilin Yang ◽  
Ping Wu ◽  
Catherine C. L. Wong ◽  
...  
Keyword(s):  
Aortic Dissection ◽  
Aortic Arch ◽  
Proteomic Analysis ◽  
Molecular Mechanisms ◽  
Acute Aortic Dissection ◽  
High Rate ◽  
Differential Abundance ◽  
Healthy Donors ◽  
Novel Biomarkers ◽  
Abundance Proteins

Background. Acute aortic dissection (AAD) is a devastating cardiovascular disease with a high rate of disability and mortality. This disease often rapidly progresses to fatal multiple organ hypoperfusion, and the incidence has been increasing in recent years. However, the molecular mechanisms have yet to be clarified. This study is aimed at identifying the differential abundance proteins (DAPs) of aortic arch tissues in patients with AAD by proteomics and select possible proteins involved in AAD pathogenesis. Methods. The fresh aortic arch tissues obtained from 5 AAD patients and 1 healthy donor were analyzed by amine-reactive tandem mass tag (TMT) labelling and mass spectrometry; then, the pathological sections of another 10 healthy donors and 20 AAD patients were chosen to verify the proteomic results by immunohistochemistry. Results. Of 809 proteins identified by proteomic analysis, 132 differential abundance proteins (DAPs) were screened, of which 100 proteins were significantly downregulated while 32 upregulated. Among 100 downregulated proteins, two proteins with known function, integrin alpha 3 (ITGA-3) and ITGA-5, were selected as target proteins involved in AAD pathogenesis. Two target DAPs were verified by immunohistochemisty, and the results showed that the integrated option density (IOD) of ITGA-3 and ITGA-5 in AAD patients was significantly lower than that in healthy donors, which were consistent with the proteomic results (P<0.001). Conclusion. ITGA-3 and ITGA-5 represent novel biomarkers for the pathogenesis of AAD and might be a therapeutic target in the future.

scholarly journals Growth Factor Deregulation and Emerging Role of Phosphatases in Diabetic Peripheral Artery Disease

2021 ◽  
Vol 7 ◽  
Author(s):  
Clément Mercier ◽  
Marina Rousseau ◽  
Pedro Geraldes
Keyword(s):  
Growth Factor ◽  
Peripheral Artery Disease ◽  
Molecular Mechanisms ◽  
Diabetic Patients ◽  
Peripheral Artery ◽  
Protein Tyrosine ◽  
Collateral Arteries ◽  
Increased Risk ◽  
Artery Disease

Peripheral artery disease is caused by atherosclerosis of lower extremity arteries leading to the loss of blood perfusion and subsequent critical ischemia. The presence of diabetes mellitus is an important risk factor that greatly increases the incidence, the progression and the severity of the disease. In addition to accelerated disease progression, diabetic patients are also more susceptible to develop serious impairment of their walking abilities through an increased risk of lower limb amputation. Hyperglycemia is known to alter the physiological development of collateral arteries in response to ischemia. Deregulation in the production of several critical pro-angiogenic factors has been reported in diabetes along with vascular cell unresponsiveness in initiating angiogenic processes. Among the multiple molecular mechanisms involved in the angiogenic response, protein tyrosine phosphatases are potent regulators by dephosphorylating pro-angiogenic tyrosine kinase receptors. However, evidence has indicated that diabetes-induced deregulation of phosphatases contributes to the progression of several micro and macrovascular complications. This review provides an overview of growth factor alterations in the context of diabetes and peripheral artery disease, as well as a description of the role of phosphatases in the regulation of angiogenic pathways followed by an analysis of the effects of hyperglycemia on the modulation of protein tyrosine phosphatase expression and activity. Knowledge of the role of phosphatases in diabetic peripheral artery disease will help the development of future therapeutics to locally regulate phosphatases and improve angiogenesis.

MicroRNAs as novel biomarkers in depression, diabetes, and cardiovascular diseases

2018 ◽  
Author(s):  
Mohamad M. Almedawar ◽  
Richard C. Siow ◽  
Henning Morawietz
Keyword(s):  
Diabetes Mellitus ◽  
Cardiovascular Diseases ◽  
Microvascular Dysfunction ◽  
Diabetic Patients ◽  
Cardiovascular Disorders ◽  
Vascular Depression ◽  
Symptoms Of Depression ◽  
Clinical Complications ◽  
Increased Risk ◽  
Novel Biomarkers

Diabetic, depressive, and cardiovascular disorders are leading causes of morbidity. In diabetics, symptoms of depression are associated with increased clinical complications. Diabetes mellitus is a major risk factor of cardiovascular diseases (CVDs). The vascular depression hypothesis suggests that CVD can increase the risk of depression or exacerbate depression-related conditions. Several studies found a strong correlation between depression and pre-existing vascular disease and vice versa. Recent studies implicate microvascular dysfunction in the pathophysiology of depression and CVD. In addition, microRNAs are potent regulators of gene expression in physiological and pathophysiological processes affecting the microcirculation. We propose an interaction between diabetes mellitus, depression, and CVD involving changes in microcirculation and microRNA expression. Hence, studies are warranted to develop novel microRNA therapeutics and biomarkers to identify diabetic patients at increased risk of developing clinical complications of depression.

The Capacity of a Specific Anti-Streptococcus Mutans Monoclonal Antibodies Test to Identify the Diabetic Patients with Increased Risk of Periodontal Disease

2017 ◽  
Vol 68 (11) ◽  
pp. 2556-2559
Author(s):  
Mona Ionas ◽  
Sebastian Ioan Cernusca Mitariu ◽  
Adela Dancila ◽  
Tiberiu Horatiu Ionas ◽  
Raluca Monica Comaneanu ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Periodontal Disease ◽  
Streptococcus Mutans ◽  
Mutans Streptococci ◽  
Diabetic Patients ◽  
A Value ◽  
Salivary Level ◽  
Increased Risk ◽  
The Status

By means of a specific anti-Streptococcus mutans monoclonal antibodies test we want to identify the diabetic patients which have an increased risk to develop the periodontal disease. The highest percentage, of 88.1% of all patients included in this study represents the subjects with a level greater than 500,000 cfu / mL of streptococcus mutans. The Kruskal-Wallis test reveals a value of p = 0.283 resulted from the status of diabetes in patients and the level of streptococcus mutans in saliva. In conclusion, the status of diabetes in patients seems not to influence the salivary level of mutans streptococci determined with the method used in our study.

Circulating Stem/Progenitor Cells as Prognostic Biomarkers in Macro- and Microvascular Disease: A Narrative Review of Prospective Observational Studies

2018 ◽  
Vol 25 (35) ◽  
pp. 4507-4517 ◽  
Author(s):  
Mauro Rigato ◽  
Gian Paolo Fadini
Keyword(s):  
Cardiovascular Disease ◽  
Progenitor Cells ◽  
Cardiovascular Events ◽  
Observational Studies ◽  
English Language ◽  
Microvascular Disease ◽  
Patient Characteristics ◽  
Diabetic Patients ◽  
Increased Risk ◽  
Cell Phenotypes

Background: Circulating progenitor cells (CPCs) and endothelial progenitor cells (EPCs) are immature cells involved in vascular repair and related to many aspects of macro and microvascular disease. <p> Objective: We aimed to review studies reporting the prognostic role of CPCs/EPCs measurement on development of cardiovascular disease and microangiopathy. <p> Methods and Results: We reviewed the English language literature for prospective observational studies reporting the future development of cardiovascular disease or microangiopathy in patients having a baseline determination of CPCs/EPCs. We retrieved 34 studied reporting on cardiovascular outcomes and 2 studies reporting on microvascular outcomes. Overall, a reduced baseline level of CPCs/EPCs was associated with a significant increased risk of cardiovascular events, all-cause death, and onset/progression of microangiopathy. The most predictive phenotypes were CD34+ and CD34+CD133+. The main limitation was related to the high heterogeneity among studies in terms of patient characteristics and cell phenotypes. <p> Conclusion: The present review shows that a reduced level of circulating progenitor cells is a risk factor for the development of future cardiovascular events and death. In addition, low CPCs/EPCs levels predict the onset or worsening of microalbuminuria and retinopathy in diabetic patients.

The Role of Vascular Aging in Atherosclerotic Plaque Development and Vulnerability

2019 ◽  
Vol 25 (29) ◽  
pp. 3098-3111 ◽  
Author(s):  
Luca Liberale ◽  
Giovanni G. Camici
Keyword(s):  
Atherosclerotic Plaque ◽  
Molecular Mechanisms ◽  
Driving Forces ◽  
Plaque Burden ◽  
Vascular Aging ◽  
Age Related ◽  
Plaque Development ◽  
Increased Risk ◽  
The Impact ◽  
Over Time

Background: The ongoing demographical shift is leading to an unprecedented aging of the population. As a consequence, the prevalence of age-related diseases, such as atherosclerosis and its thrombotic complications is set to increase in the near future. Endothelial dysfunction and vascular stiffening characterize arterial aging and set the stage for the development of cardiovascular diseases. Atherosclerotic plaques evolve over time, the extent to which these changes might affect their stability and predispose to sudden complications remains to be determined. Recent advances in imaging technology will allow for longitudinal prospective studies following the progression of plaque burden aimed at better characterizing changes over time associated with plaque stability or rupture. Oxidative stress and inflammation, firmly established driving forces of age-related CV dysfunction, also play an important role in atherosclerotic plaque destabilization and rupture. Several genes involved in lifespan determination are known regulator of redox cellular balance and pre-clinical evidence underlines their pathophysiological roles in age-related cardiovascular dysfunction and atherosclerosis. Objective: The aim of this narrative review is to examine the impact of aging on arterial function and atherosclerotic plaque development. Furthermore, we report how molecular mechanisms of vascular aging might regulate age-related plaque modifications and how this may help to identify novel therapeutic targets to attenuate the increased risk of CV disease in elderly people.

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