Targeting delivery of miR-146a via IMTP modified milk exosomes exerted cardioprotective effects by inhibiting NF-κB signaling pathway after myocardial ischemia-reperfusion injury.

Reperfusion therapy is critical for saving heart muscle after myocardial infarction, but the process of restoring blood flow can itself exacerbate injury to the myocardium. This phenomenon is known as myocardial ischemia-reperfusion injury (MIRI), which includes oxidative stress, inflammation, and further cell death. microRNA-146a (miR-146a) is known to play a significant role in regulating the immune response and inflammation, and has been studied for its potential impact on the improvement of heart function after myocardial injury. However, the delivery of miR-146a to the heart in a specific and efficient manner remains a challenge as extracellular RNAs are unstable and rapidly degraded. Milk exosomes (MEs) have been proposed as ideal delivery platform for miRNA-based therapy as they can protect miRNAs from RNase degradation. In this study, the effects of miR-146a containing MEs (MEs-miR-146a) on improvement of cardiac function were examined in a rat model of MIRI. To enhance the targeting delivery of MEs-miR-146a to the site of myocardial injury, the ischemic myocardium-targeted peptide IMTP was modified onto the surfaces, and whether the modified MEs-miR-146a could exert a better therapeutic role was examined by echocardiography, myocardial injury indicators and the levels of inflammatory factors. Furthermore, the expressions of miR-146a mediated NF-κB signaling pathway-related proteins were detected by western blotting and qRT-PCR to further elucidate its mechanisms. MiR-146 mimics were successfully loaded into the MEs by electroporation at a square wave 1000 V voltage and 0.1 ms pulse duration. MEs-miR-146a can be up-taken by cardiomyocytes and protected the cells from oxygen glucose deprivation/reperfusion induced damage in vitro. Oral administration of MEs-miR-146a decreased myocardial tissue apoptosis and the expression of inflammatory factors and improved cardiac function after MIRI. The miR-146a level in myocardium tissues was significantly increased after the administration IMTP modified MEs-miR-146a, which was higher than that of the MEs-miR-146a group. In addition, intravenous injection of IMTP modified MEs-miR-146a enhanced the targeting to heart, improved cardiac function, reduced myocardial tissue apoptosis and suppressed inflammation after MIRI, which was more effective than the MEs-miR-146a treatment. Moreover, IMTP modified MEs-miR-146a reduced the protein levels of IRAK1, TRAF6 and p-p65. Therefore, IMTP modified MEs-miR-146a exerted their anti-inflammatory effect by inhibiting the IRAK1/TRAF6/NF-κB signaling pathway. Taken together, our findings suggested miR-146a containing MEs may be a promising strategy for the treatment of MIRI with better outcome after modification with ischemic myocardium-targeted peptide, which was expected to be applied in clinical practice in future.

Screening and identification of effective components from modified Taohong Siwu decoction for protecting H9c2 cells from damage.

We found that modified Taohong Siwu decoction (MTHSWD) had cardioprotective effects after myocardial ischemia-reperfusion injury. This study was to screen the effective components of MTHSWD that have protective effects on H9c2 cell injury through H2O2 injury model. Fifty-three active components were screened by CCK8 assay to detect cell viability. The anti-oxidative stress ability was evaluated by detecting the levels of total superoxide dismutase (SOD) and malondialdehyde (MDA) in cells. The anti-apoptotic effect was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL). Finally, the phosphorylation levels of ERK, AKT, and P38MAPK were detected by WB (Western blot) to study the protective mechanism of effective monomers against H9c2 cell injury. Among the 53 active ingredients of MTHSWD, ginsenoside Rb3, levistilide A, ursolic acid, tanshinone I, danshensu, dihydrotanshinone I, and astragaloside I could significantly increase the viability of H9c2 cells. The results of SOD and MDA showed that ginsenoside Rb3, tanshinone I, danshensu, dihydrotanshinone I, and tanshinone IIA could significantly reduce the content of lipid peroxide in cells. TUNEL results showed that ginsenoside Rb3, tanshinone I, danshensu, dihydrotanshinone I, and tanshinone IIA reduced apoptosis to varying degrees. The tanshinone IIA, ginsenoside Rb3, dihydrotanshinone I, and tanshinone I reduced the phosphorylation levels of P38MAPK and ERK in H9c2 cells induced by H2O2, and the phosphorylation level of ERK was also significantly reduced by danshensu. At the same time, tanshinone IIA, ginsenoside Rb3, dihydrotanshinone I, tanshinone I, and danshensu significantly increased AKT phosphorylation level in H9c2 cells. In conclusion, the effective ingredients in MTHSWD provide basic basis and experimental reference for the prevention and treatment of cardiovascular diseases.

Prevalence of Fatigue and Its Association With Quality of Life Among Frontline Clinicians in Ophthalmology and Otolaryngology Departments During the COVID-19 Pandemic.

Background: The coronavirus disease 2019 (COVID-19) pandemic has caused psychological distress and heavy burden in medical professionals. This study examined the prevalence of fatigue and its association with quality of life (QOL) in clinicians working in ophthalmology and otolaryngology departments during the COVID-19 pandemic in China. Methods: This was a cross-sectional national online survey conducted between March 15 and March 20, 2020 in China. The severity of fatigue, depression and QOL were measured using the Numeric Rating Scale (NRS), the 9-item Patient Health Questionnaire (PHQ-9), and the World Health Organization Quality of Life Questionnaire-Brief Version (WHOQOL-BREF), respectively. Results: In total, 3,912 clinicians completed the survey (2,155 in ophthalmology department, and 1,757 in otolaryngology department); 2,049 [52.4%; 95% confidence interval (CI) = 50.8-53.9%] reported fatigue (NRS score ≥ 4). Multiple logistic regression analysis revealed that junior clinicians [Odds ratio (OR) = 0.82, 95% CI = 0.68-1.00, P = 0.045] had lower risk of fatigue; while clinicians working in tertiary hospitals (OR = 1.23, 95% CI = 1.02-1.49, P = 0.029), and the presence of more severe depressive symptoms (PHQ-9 total score ≥ 5; OR = 7.40, 95% CI = 6.29-8.70, P < 0.001) were independently associated with higher risk of fatigue. After controlling for covariates, clinicians with fatigue had significantly lower QOL compared with those without [F (1, 3, 911) = 283.75, P < 0.001]. Conclusion: Fatigue was common in clinicians working in ophthalmology and otolaryngology departments during the COVID-19 pandemic. Considering the negative impact of fatigue on clinicians' QOL, health authorities and policymakers should conduct regular screening for fatigue and develop preventive strategies for frontline clinicians working under excessive stress.

Prevalence of depression and its impact on quality of life in frontline otorhinolaryngology nurses during the COVID-19 pandemic in China.

OBJECTIVE: Exposure to the coronavirus disease 2019 (COVID-19) was associated with high risk of mental health problems among frontline nurses. This study examined the prevalence of depressive symptoms (depression hereafter) and its impact on quality of life (QOL) in otorhinolaryngology (ENT) nurses during the COVID-19 pandemic in China. METHODS: An online study was conducted between March 15 and March 20, 2020. Depression and QOL were assessed using standardized instruments. RESULTS: A total of 1,757 participants were recruited. The prevalence of depression was 33.75% (95% CI: 31.59%-35.97%). Results emerging from multiple logistic regression analysis showed that direct care of COVID-19 patients (OR: 1.441, 95% CI: 1.031-2.013, P = 0.032), and current smoking (OR: 2.880, 95% CI: 1.018-8.979, P = 0.048) were significantly associated with depression. After controlling for covariates, ENT nurses with depression had a lower overall QOL compared to those without depression (F(1, 1757)= 536.80, P < 0.001). CONCLUSIONS: Depression was common among ENT nurses during the COVID-19 pandemic in China. Considering the negative impact of depression on QOL and care quality, regular screening for depression should be conducted in ENT nurses and treatment should be provided.