Hong KS, et al. Yonsei Med J. 2020 May;61(5):431-437. https://doi.org/10.3349/ymj.2020.61.5.431

Jang JG, et al. J Korean Med Sci. 2020 Jun;35(25):e234. https://doi.org/10.3346/jkms.2020.35.e234

Jang JG, et al. J Korean Med Sci. 2020 Apr;35(23):e209. https://doi.org/10.3346/jkms.2020.35.e209

In response to the coronavirus disease-19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), global efforts are focused on the development of new therapeutic interventions. For the treatment of COVID-19, selective lung-localizing strategies hold tremendous potential, as SARS-CoV-2 invades the lung via ACE2 receptors and causes severe pneumonia. Similarly, recent reports have shown the association of COVID-19 with decreased 25-hydroxycholesterol (25-HC) and increased cytokine levels. This mechanism, which involves the activation of inflammatory NF-κB- and SREBP2-mediated inflammasome signaling pathways, is believed to play a crucial role in COVID-19 pathogenesis, inducing acute respiratory distress syndrome (ARDS) and sepsis. To resolve those clinical conditions observed in severe SARS-CoV-2 patients, we report 25-HC and didodecyldimethylammonium bromide (DDAB) nanovesicles (25-HC@DDAB) as a COVID-19 drug candidate for the restoration of intracellular cholesterol level and suppression of cytokine storm. Our data demonstrate that 25-HC@DDAB can selectively accumulate the lung tissues and effectively downregulate NF-κB and SREBP2 signaling pathways in COVID-19 patient-derived PBMCs, reducing inflammatory cytokine levels. Altogether, our findings suggest that 25-HC@DDAB is a promising candidate for the treatment of symptoms associated with severe COVID-19 patients, such as decreased cholesterol level and cytokine storm.

Jang JG, et al. Tuberc Respir Dis. 2014 Aug;77(2):90-93. http://dx.doi.org/10.4046/trd.2014.77.2.90

Background: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in patients with chronic obstructive pulmonary disease (COPD) and is independently associated with cardiometabolic comorbidities and systemic inflammation. Although several factors are associated with NAFLD, the influence of sarcopenia on NAFLD has not been fully determined in patients with COPD. We explored whether sarcopenia is associated with NAFLD in a COPD population. Methods: Data from the Korean National Health and Nutrition Examination Surveys 2008– 2011 were analyzed. The subjects were defined as having NAFLD when they had a hepatic steatosis index (HSI) score > 36, which is a previously validated NAFLD prediction score. Sarcopenia_BMI (=total appendicular skeletal muscle mass [kg]/body mass index [kg/m²]), sarcopenia_BW (=total appendicular skeletal muscle mass [kg]/body weight [kg] × 100), and sarcopenia_height (= total appendicular skeletal muscle mass (kg)/height² (m)) measured using dual-energy X-ray absorptiometry was used to diagnose sarcopenia. Results: NAFLD was identified in 124 (14.6%) of 850 COPD subjects using the HSI. Multivariable logistic analyses adjusted for age, sex, hypertension, diabetes mellitus (DM), forced vital capacity (FVC), and metabolic syndrome demonstrated that sarcopenia (sarcopenia_BMI, odds ratio [OR] = 1.95; 95% confidence interval [CI], 1.11– 3.46, p = 0.022; sarcopenia_BW, OR = 2.25; 95% CI, 1.30– 3.92, p = 0.004) was associated with NAFLD in patients with COPD. The proportion of sarcopenia_BMI was higher in patients with a high fibrotic burden from NAFLD (Q3, Q4) than in subjects with a low fibrotic burden from NALFD (Q1, Q2) (54.8% vs 24.2%, p = 0.024). The proportion of sarcopenia_BW was also higher in patients with a high fibrotic burden from NAFLD than in patients with a low fibrotic burden from NAFLD (51.6% vs 30.6%, p = 0.029). Conclusion: Sarcopenia was associated with an increased risk for NAFLD in patients with COPD, independent of age, sex, lung function, and metabolic factors. Sarcopenic COPD was also associated with a high fibrotic burden in NAFLD patients. Pulmonologists should be aware of possible liver comorbidities in the sarcopenic COPD phenotype.