Vasculogenic mimicry (VM), a new pattern of tumor microcirculation, is important for the growth and progression of tumors. Epithelial-mesenchymal transition (EMT) is pivotal in malignant tumor progression and VM formation. With increasing knowledge of cancer stem cell (CSC) phenotypes and functions, increasing evidence suggests that CSCs are involved in VM formation. Recent studies have indicated that EMT is relevant to the acquisition and maintenance of stem cell-like characteristics. Thus, in this review we discuss the correlation between CSCs, EMT and VM formation.
P62, also called sequestosome1 (SQSTM1), is the selective cargo receptor for autophagy to degenerate misfolded proteins. It has also been found to assist and connect parkin in pink1/parkin mitophagy pathway. Previous studies showed that p62 was in association with neurodegenerative diseases, and one of the diseases pathogenesis is P62 induced autophagy and mitophagy dysfunction. Autophagy is an important process to eliminate misfolded proteins. Intracellular aggregation including α-synuclein, Huntingtin, tau protein and ß-amyloid (Aß) protein are the misfolded proteins found in PD, HD and AD, respectively. P62 induced autophagy failure significantly accelerates misfolded protein aggregation. Mitophagy is the special autophagy, functions as the selective scavenger towards the impaired mitochondria. Mitochondrial dysfunction was confirmed greatly contribute to the occurrence of neurodegenerative diseases. Through assistance and connection with parkin, P62 is vital for regulating mitophagy, thus, aberrant P62 could influence the balance of mitophagy, and further disturb mitochondrial quality control. Therefore, accumulation of misfolded proteins leads to the aberrant P62 expression, aberrant P62 influence the balance of mitophagy, forming a vicious circle afterwards. In this review, we summarize the observations on the function of P62 relevant to autophagy and mitophagy in neurodegenerative diseases, hoping to give some clear and objective opinions to further study.
Background
Coronavirus disease (COVID-19) has resulted in considerable morbidity and mortality worldwide. Thyroid hormones play a key role in modulating metabolism and the immune system. However, the prevalence of thyroid dysfunction (TD) and its association with the prognosis of COVID-19 have not yet been elucidated. In this study, we seek to address this gap and understand the link between TD and COVID-19.
Methods
Herein, we enrolled patients who were hospitalised with COVID-19 and had normal or abnormal thyroid function test results at the West Court of Union Hospital in Wuhan, China, between 29 January and 26 February 2020. We carried out follow up examinations until 26 April 2020. Data on clinical features, treatment strategies, and prognosis were collected and analysed. TD was defined as an abnormal thyroid function test result, including overt thyrotoxicosis, overt hypothyroidism, subclinical hypothyroidism, subclinical hyperthyroidism, and euthyroid sick syndrome.
Results
A total of 25 and 46 COVID-19 patients with and without TD, respectively, were included in the study. COVID-19 patients with TD had significantly higher neutrophil counts and higher levels of C-reactive protein, procalcitonin, lactate dehydrogenase, serum creatine kinase, aspartate transaminase, and high-sensitive troponin I and a longer activated partial thromboplastin time but lower lymphocyte, platelet, and eosinophil counts. A longitudinal analysis of serum biomarkers showed that patients with TD presented persistently high levels of biomarkers for inflammatory response and cardiac injury. COVID-19 patients with TD were more likely to develop a critical subtype of the disease. Patients with TD had a significantly higher fatality rate than did those without TD during hospitalisation (20% vs 0%, P<0.0001). Patients with TD were more likely to stay in the hospital for more than 28 days than were those without TD (80% vs 56.52%, P=0.048).
Conclusions
Our preliminary findings suggest that TD is associated with poor outcomes in patients with COVID-19.
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