Congenital Large Cutaneous Hemangioma with Arteriovenous and Arterioarterial Malformations: A Novel Association

BACKGROUND Coronavirus disease (COVID-19) is a budding infectious disease that has affected various countries globally. OBJECTIVE The aim of this study was to analyze the effect of COVID-19 disease on liver and kidney functions and to determine their association with the severity and mortality of disease METHODS A total of 100 confirmed COVID-19 adult patients from Madinah city of Saudi Arabia hospitalized between April 28, and June 30, 2020 were included,and categorized into asymptomatic,mild to moderate and severely ill patients.We analyzed the clinical status of liver and renal functioning in all of the three groups. RESULTS The majority of patients (51%) were diagnosed with mild to moderate disease, 27% of patients were severely ill and 22% of patients were asymptomatic.The liver and renal functional analysis showed that the severity of the COVID-19 patients were significantly associated with the kidney and renal impairments exhibiting higher levels of ALT, AST, Creatinine, Urea levels (P < 0.05). Furthermore, in this study, a novel association is found between high Na and Cl levels with the severely ill COVID-19 patients. CONCLUSIONS We concluded from the present study that a significant percentage of COVID-19 patients continued to have a normal liver and renal function during the course of their disease. Nevertheless, severely ill COVID-19 patients were more prone to have abnormal liver and renal functions. During the course of treatment, the patients had a gradual normalization of their liver and kidney parameters and subsequently achieved a complete normal liver and renal functions upon discharge with no mortality.

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EGFRvIII Promotes Cell Survival during Endoplasmic Reticulum Stress through a Reticulocalbin 1-Dependent Mechanism

Cancers ◽

10.3390/cancers13061198 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1198

Author(s):

Juliana Gomez ◽

Zammam Areeb ◽

Sarah F. Stuart ◽

Hong P. T. Nguyen ◽

Lucia Paradiso ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Cell Viability ◽

Er Stress ◽

Cell Survival ◽

Glioblastoma Cells ◽

Over Expression ◽

Stress Markers ◽

Apoptotic Protein ◽

Novel Association ◽

Reduced Activity

Reticulocalbin 1 (RCN1) is an endoplasmic reticulum (ER)-residing protein, involved in promoting cell survival during pathophysiological conditions that lead to ER stress. However, the key upstream receptor tyrosine kinase that regulates RCN1 expression and its potential role in cell survival in the glioblastoma setting have not been determined. Here, we demonstrate that RCN1 expression significantly correlates with poor glioblastoma patient survival. We also demonstrate that glioblastoma cells with expression of EGFRvIII receptor also have high RCN1 expression. Over-expression of wildtype EGFR also correlated with high RCN1 expression, suggesting that EGFR and EGFRvIII regulate RCN1 expression. Importantly, cells that expressed EGFRvIII and subsequently showed high RCN1 expression displayed greater cell viability under ER stress compared to EGFRvIII negative glioblastoma cells. Consistently, we also demonstrated that RCN1 knockdown reduced cell viability and exogenous introduction of RCN1 enhanced cell viability following induction of ER stress. Mechanistically, we demonstrate that the EGFRvIII-RCN1-driven increase in cell survival is due to the inactivation of the ER stress markers ATF4 and ATF6, maintained expression of the anti-apoptotic protein Bcl-2 and reduced activity of caspase 3/7. Our current findings identify that EGFRvIII regulates RCN1 expression and that this novel association promotes cell survival in glioblastoma cells during ER stress.

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Novel association of congenital neutropenia with a homozygous stop-gain variant in SENP7

Molecular Genetics and Metabolism ◽

10.1016/s1096-7192(21)00433-9 ◽

2021 ◽

Vol 132 ◽

pp. S227-S228

Author(s):

Erica Sanford Kobayashi ◽

Nanda Ramchandar ◽

John Teijaro ◽

Julie Cakici ◽

Emily Farrow ◽

...

Keyword(s):

Congenital Neutropenia ◽

Novel Association

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CBIO-05. LIPID METABOLIC REPROGRAMMING SENSITIZES A MOLECULARLY-DEFINED SUBSET OF GLIOBLASTOMAS TO FERROPTOSIS

Neuro-Oncology ◽

10.1093/neuonc/noaa215.065 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii16-ii16

Author(s):

Danielle Morrow ◽

David Nathanson ◽

Timothy Cloughesy ◽

Robert Prins ◽

Nicholas Bayley ◽

...

Keyword(s):

Lipid Metabolism ◽

Lipid Droplets ◽

Metabolic Reprogramming ◽

Membrane Phospholipids ◽

Molecular Alterations ◽

Lipidomic Analysis ◽

Novel Association ◽

Therapeutic Opportunity ◽

Dependent Cell ◽

Main Components

Abstract Cancers, including the universally lethal glioblastoma (GBM), have reprogrammed lipid metabolism to fuel tumor growth. However, the molecular alterations responsible for aberrant lipid metabolism, and the potential for identifying new therapeutic opportunities are not fully understood. To systematically investigate the GBM lipidome, we performed integrated transcriptomic, genomic and shotgun lipidomic analysis of an extensive library of molecularly diverse patient-derived GBM samples. Using this comprehensive approach, we discovered two GBM sub-groups defined by their combined molecular and lipidomic profile. Triacylglycerides (TAGs) enriched in polyunsaturated fatty acids (PUFAs) were among the most significantly altered lipids between the two groups of GBM tumors. TAGs are the main components of lipid droplets, which sequester PUFA-TAGs away from membrane phospholipids where their peroxidation can lead to ferroptosis – a regulated from of PUFA-peroxidation dependent cell death. Accordingly, the GBM subgroup with a depletion of PUFA TAGs showed heightened sensitivity to ferroptosis. Our findings suggest a novel association between specific molecular signatures of GBM, lipid metabolism and ferroptosis. This relationship may present a new therapeutic opportunity to target reprogrammed lipid metabolism in a molecularly-defined subset of GBMs.

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Ventilatory defects and treatable traits in very elderly patients

Science Progress ◽

10.1177/00368504211013171 ◽

2021 ◽

Vol 104 (2) ◽

pp. 003685042110131

Author(s):

João Gaspar-Marques ◽

Teresa Palmeiro ◽

Iolanda Caires ◽

Paula Leiria Pinto ◽

Nuno Neuparth ◽

...

Keyword(s):

Cognitive Impairment ◽

Elderly Patients ◽

Elderly Care ◽

Airflow Limitation ◽

The Novel ◽

Z Score ◽

Very Elderly ◽

Chronic Respiratory Diseases ◽

Novel Association ◽

Peripheral Pulse

Though the approach used to classify chronic respiratory diseases is changing to a treatable-traits (TT) approach, data regarding very elderly patients is lacking. The objectives of this study were to assess TT frequency in very elderly patients and to study the link between extrapulmonary TT and ventilatory defects. Individuals (≥75 years) residing in elderly care centres answered a standardised questionnaire, underwent spirometry, atopy and fractional exhaled nitric oxide assessments and had their blood pressure and peripheral pulse oximetry measured. Pulmonary, extrapulmonary and behavioural TT were evaluated. Outcome variables were an airflow limitation (post-bronchodilator z-score FEV1/FVC<−1.64) and a restrictive spirometry pattern (z-score FEV1/FVC ≥ +1.64 and z-score FVC<−1.64). Seventy-two percent of the individuals who took part in the study ( n = 234) were women, and the median age of participants was 86 (IQR: 7.4). At least one pulmonary TT was identified in 105 (44.9%) individuals. The most frequent extrapulmonary TTs were: persistent systemic inflammation (47.0%), anaemia (34.4%), depression (32.5%) and obesity (27.4). Airflow limitation was exclusively associated with smoking (OR 5.03; 95% CI 1.56–16.22). A restrictive spirometry pattern was associated with cognitive impairment (OR: 3.89; 95% CI: 1.55–9.79). A high frequency of various TTs was found. The novel association between a restrictive spirometry pattern and cognitive impairment highlights the urgency of clinical research on this vulnerable age group.

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