Translational research : the journal of laboratory and clinical medicine
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Chronic low-grade inflammation has been proposed as a linking mechanism between obesity and the development of inflammation-related conditions such as insulin resistance and cardiovascular disease. Despite major advances in the last 2 decades, the complex relationship between inflammation and obesity remains poorly understood. Therefore, we aimed to identify novel inflammation-related proteins associated with adiposity. ⋯ We confirmed previously reported associations with CCL19, CCL28, FGF-21, HGF, IL-10RB, IL-18, IL-18R1, IL-6, SCF, and VEGF-A. The majority of the identified inflammation-related proteins were associated with visceral fat as well as with the accumulation of adipose tissue in the abdomen and the trunk. In conclusion, our study provides new insights into the immune dysregulation observed in obesity that might help uncover pathophysiological mechanisms of disease development.
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CDKN2C/p18 (Cyclin-Dependent Kinase Inhibitor 2C) is a cell growth regulator that controls cell cycle progression and has previously been associated with increased risk for type II diabetes (T2D) and reduced peripheral adipose tissue (AT) storage capacity. This study explored the role of CDKN2C in AT lipid and glucose metabolism in T2D. Expression of CDKN2C and other genes was analyzed by transcriptomics, or real-time PCR in subcutaneous AT (SAT) samples obtained from T2D and control subjects matched for sex, age and BMI and also in paired SAT and omental AT (OAT) samples. ⋯ Knockdown of CDKN2C did not affect the percentage of differentiating cells compared to wild type cultures. However, CDKN2C knockdown cultures had significantly lower expression of differentiation markers CEBPA, ADIPOQ and FASN and transiently reduced lipid accumulation per adipocyte during differentiation. Our findings suggest that adipose CDKN2C expression might be reduced as a consequence of insulin resistance and obesity, and this can further contribute to impairment of SAT lipid storage.
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Patients with cancers have been severely affected by the COVID-19 pandemic. This is highlighted by the adverse outcomes in cancer patients with COVID-19 as well as by the impact of the COVID-19 pandemic on cancer care. Patients with cancer constitute a heterogeneous population that exhibits distinct mechanisms of immune dysfunction, associated with distinct systemic features of hot (T-cell-inflamed/infiltrated) and cold (Non-T-cell-inflamed and/or infiltrated) tumors. ⋯ This review will focus on defining the known contributions of soluble pro- and anti-inflammatory mediators on immune function including altered T-cells and B-cells responses and as well on how these factors modulate the expression of SARS-CoV-2 receptor ACE2, TMPRSS2 expression, and lymph node fibrosis in cancer patients. We will propose immune mechanisms that underlie the distinct courses of SARS-CoV-2 infection in cancer patients and impact on the success of immune based therapies that have significantly improved cancer outcomes. Better understanding of the immune mechanisms prevalent in cancer patients that are associated to the outcomes of SARS-CoV-2 infection will help to identify the high-risk cancer patients and develop immune-based approaches to prevent significant adverse outcomes by targeting these pathways.
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The current era of COVID-19 is characterized by emerging variants of concern, waning vaccine- and natural infection-induced immunity, debate over the timing and necessity of vaccine boosting, and the emergence of post-acute sequelae of SARS-CoV-2 infection. As a result, there is an ongoing need for research to promote understanding of the immunology of both natural infection and prevention, especially as SARS-CoV-2 immunology is a rapidly changing field, with new questions arising as the pandemic continues to grow in complexity. The next phase of COVID-19 immunology research will need focus on clearer characterization of the immune processes defining acute illness, development of a better understanding of the immunologic processes driving protracted symptoms and prolonged recovery (ie, post-acute sequelae of SARS-CoV-2 infection), and a growing focus on the impact of therapeutic and prophylactic interventions on the long-term consequences of SARS-CoV-2 infection. In this review, we address what is known about the long-term immune consequences of SARS-CoV-2 infection and propose how experience studying the translational immunology of other infections might inform the approach to some of the key questions that remain.
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While the coronavirus disease 19 (COVID-19) pandemic has transformed the medical and scientific communites since it was first reported in late 2019, we are only beginning to understand the chronic health burdens associated with this disease. Although COVID-19 is a multi-systemic disease, the lungs are the primary source of infection and injury, resulting in pneumonia and, in severe cases, acute respiratory distress syndrome (ARDS). Given that pulmonary fibrosis is a well-recognized sequela of ARDS, many have questioned whether COVID-19 survivors will face long-term pulmonary consequences. This review is aimed at integrating our understanding of the pathophysiologic mechanisms underlying fibroproliferative ARDS with our current knowledge of the pulmonary consequences of COVID-19 disease.