Glutaredoxin systems

Glutaredoxins utilize the reducing power of glutathione to maintain and regulate the cellular redox state and redox-dependent signaling pathways, for instance, by catalyzing reversible protein S-glutathionylation. Due to the general importance of these processes, glutaredoxins have been implied in various physiological and disease-related conditions, such as immune defense, cardiac hypertrophy, hypoxia-reoxygenation insult, neurodegeneration and cancer development, progression as well as treatment. The past years have seen an impressive gain of knowledge regarding new glutaredoxin systems and functions. This is true both with respect to new functions in redox regulation and also with respect to unexpected new ties to iron metabolism and iron–sulfur cluster biosynthesis. The aim of this review is to provide a state-of-the-art overview over these recent discoveries with a focus on aspects related to human health.     

Euthyroid Sick Syndrome as a Prognostic Indicator of COVID-19 Pulmonary Involvement,Associated With Poorer Disease Prognosis and Increased Mortality

ObjectiveThe prevalence of euthyroid sick syndrome (ESS) and its association with the prognosis of COVID-19 and mortality in patients with lung involvement in COVID-19 have not yet been elucidated.MethodsClinical and laboratory data of patients with COVID-19 with or without ESS were collected retrospectively and analyzed on admission. All subjects were admitted to the Department of Internal Diseases and Clinical Pharmacology at Bieganski Hospital between December 2020 and April 2021.ResultsIn total, 310 medical records of patients with COVID-19 were analyzed retrospectively. Among 215 enrolled patients, 82 cases of ESS were diagnosed. The patients with ESS had higher pro-inflammatory factor levels, longer hospitalizations, and a higher risk of requiring high-flow nasal oxygen therapy or intubation than the patients without ESS. The Kaplan-Meier curve indicated that the patients with ESS had a lower probability of survival when computed tomography showed ≤50% parenchymal involvement compared with that in patients without ESS. However, no differences in mortality were noted in those with more than 50% parenchymal involvement. The survival curve showed that ESS was associated with a higher risk of mortality during hospitalization.ConclusionESS is closely associated with a poor prognosis, including longer hospitalizations, more frequent intubation, transfer to the intensive care unit, and a higher mortality rate in patients with COVID-19. ESS is a potential prognostic predictor of survival, regardless of lung involvement in COVID-19.     

Hypoxia alters contractile protein homeostasis in L6 myotubes

Since hypoxia might contribute to the development of muscle atrophy, we wished to provide direct evidence linking hypoxia to muscle atrophy. By evaluating protein degradation and synthesis in hypoxic myotubes we found a significant reduction in total protein content. Using functional assays we observed protein degradation elevation in the first 24 h while synthesis was maintained during this period and then significantly decrease at 48 h. These results demonstrate a temporal regulation of protein homeostasis, whereby elevated protein degradation is followed by a reduction in synthesis. These results are comparable to the cellular adaptation seen during development of muscle atrophy.     

Metastatic small cell lung cancer causing biliary obstruction

We report a case with metastatic small cell lung cancer which first manifested with biliary obstruction due to metastasis. Prognosis of patients presenting with jaundice due to hepatic parenchyma involvement is thought to be poor. However, the patient was successfully treated with percutaneous transhepatic biliary drainage and combination chemotherapy with reduced dosage. We believe this to be the first such case report, despite the frequency of metastasis to the liver from small cell lung cancer.     

Models of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a major global health problem and is predicted to become the third most common cause of death by 2020. Apart from the important preventive steps of smoking cessation, there are no other specific treatments for COPD that are as effective in reversing the condition, and therefore there is a need to understand the pathophysiological mechanisms that could lead to new therapeutic strategies. The development of experimental models will help to dissect these mechanisms at the cellular and molecular level. COPD is a disease characterized by progressive airflow obstruction of the peripheral airways, associated with lung inflammation, emphysema and mucus hypersecretion. Different approaches to mimic COPD have been developed but are limited in comparison to models of allergic asthma. COPD models usually do not mimic the major features of human COPD and are commonly based on the induction of COPD-like lesions in the lungs and airways using noxious inhalants such as tobacco smoke, nitrogen dioxide, or sulfur dioxide. Depending on the duration and intensity of exposure, these noxious stimuli induce signs of chronic inflammation and airway remodelling. Emphysema can be achieved by combining such exposure with instillation of tissue-degrading enzymes. Other approaches are based on genetically-targeted mice which develop COPD-like lesions with emphysema, and such mice provide deep insights into pathophysiological mechanisms. Future approaches should aim to mimic irreversible airflow obstruction, associated with cough and sputum production, with the possibility of inducing exacerbations.