Abnormal cardiac fibrosis indicates cardiac dysfunction and poor prognosis in myocardial infarction (MI) patients. Many studies have demonstrated that the ubiquitin proteasome system (UPS) plays a significant role in the pathogenesis of fibrosis. Ubiquitin C-terminal hydrolase L1 (UCHL1), a member of the UPS, is related to fibrosis in several heart diseases. However, whether UCHL1 regulates cardiac fibrosis following MI has yet to be determined. In the present study, we found that UCHL1 was dramatically increased in infarct hearts and TGF-β1-stimulated cardiac fibroblasts (CFs). Inhibition of UCHL1 with LDN57444 (LDN) reversed the myocardial fibrosis in post-MI heart and improved cardiac function. Treatment of LDN or UCHL1 siRNA abolished the TGF-β1-induced fibrotic response of CFs. We further identified GRP78 as an interactor of UCHL1 through screening using immunoprecipitationmass spectrometer. We determined that UCHL1 interacted with glucose-regulated protein of 78 kDa (GRP78) and prompted GRP78 degradation via ubiquitination. Furthermore, we found that GRP78 was upregulated after UCHL1 knockdown and that the GRP78 inhibitor HA15 diminished the antifibrotic function exerted by UCHL1 knockdown in CFs stimulated with TGF-β1. This suggests that UCHL1 regulates cardiac fibrosis post MI through interactions with GRP78. This work identifies that the UCHL1-GRP78 axis is involved in cardiac fibrosis after MI. Myocardial infarction (MI) has been the main cause of cardiovascular diseases for centuries and remains a major issue. Although improved survival from acute MI has been observed due to the effectiveness of revascularisation and other therapies, the incidence of heart failure has increased as a consequence of adverse ventricular remodelling 1,2. Among the factors involved in ventricular remodelling, cardiac fibrosis, which results from the disequilibrium of synthesis and deregulation of extracellular matrix, is a pivotal 3,4. In the acute stage, cardiac fibrosis, is a repairing process that protects the infarct heart from rupture; at the subacute and chronic stage, in cases where cardiac fibrosis abnormally persists, it inevitably leads to cardiac dysfunction and ventricular wall stiffness increasing the risk of heart failure 4,5. Thus, it is essential to control levels of cardiac fibrosis. Cardiac fibroblasts (CFs) are central mediators of the cardiac fibrotic response 6. CFs are mainly stimulated by TGFβ-1 following MI and differentiate into activated myofibroblasts which express α-smooth muscle actin (α-SMA). This results in the secretion of a large amount of extracellular matrix, including fibronectin and collagen I (Col1), which is, in part, regulated by the activation of Smad2/3 4,7,8. To date, no studies have fully elucidated how this process is regulated. The ubiquitin proteasome system (UPS), which consists of E1 ubiquitin-activating enzymes, E2 conjugating enzymes and E3 ubiquitin ligases and deubiquitinating enzymes, is responsible for the degradation and stability of the majority of proteins 9,10. Rece...

Coronavirus disease 2019 (COVID-19) is a recently emerged disease with formidable infectivity and high mortality. Emerging data suggest that diabetes is one of the most prevalent comorbidities in patients with COVID-19. Although their causal relationship has not yet been investigated, preexisting diabetes can be considered as a risk factor for the adverse outcomes of COVID-19. Proinflammatory state, attenuation of the innate immune response, possibly increased level of ACE2, along with vascular dysfunction, and prothrombotic state in people with diabetes probably contribute to higher susceptibility for SARS-CoV-2 infection and worsened prognosis. On the other hand, activated inflammation, islet damage induced by virus infection, and treatment with glucocorticoids could, in turn, result in impaired glucose regulation in people with diabetes, thus working as an amplification loop to aggravate the disease. Therefore, glycemic management in people with COVID-19, especially in those with severe illness, is of considerable importance. The insights may help to reduce the fatality in the effort against COVID-19.

Background and ObjectiveSeveral studies assessed the efficacy of traditional Chinese medical exercise in the management of Parkinson’s disease (PD), but its role remained controversial. Therefore, the purpose of this systematic review is to evaluate the evidence on the effect of traditional Chinese medical exercise for PD.MethodsSeven English and Chinese electronic databases, up to October 2014, were searched to identify relevant studies. The PEDro scale was employed to assess the methodological quality of eligible studies. Meta-analysis was performed by RevMan 5.1 software.ResultsFifteen trials were included in the review. Tai Chi and Qigong were used as assisting pharmacological treatments of PD in the previous studies. Tai Chi plus medication showed greater improvements in motor function (standardized mean difference, SMD, -0.57; 95% confidence intervals, CI, -1.11 to -0.04), Berg balance scale (BBS, SMD, -1.22; 95% CI -1.65 to -0.80), and time up and go test (SMD, -1.06; 95% CI -1.44 to -0.68). Compared with other therapy plus medication, Tai Chi plus medication also showed greater gains in motor function (SMD, -0.78; 95% CI -1.46 to -0.10), BBS (SMD, -0.99; 95% CI -1.44 to -0.54), and functional reach test (SMD, -0.77; 95% CI -1.51 to -0.03). However, Tai Chi plus medication did not showed better improvements in gait or quality of life. There was not sufficient evidence to support or refute the effect of Qigong plus medication for PD.ConclusionsIn the previous studies, Tai Chi and Qigong were used as assisting pharmacological treatments of PD. The current systematic review showed positive evidence of Tai Chi plus medication for PD of mild-to-moderate severity. So Tai Chi plus medication should be recommended for PD management, especially in improving motor function and balance. Qigong plus medication also showed potential gains in the management of PD. However, more high quality studies with long follow-up are warrant to confirm the current findings.

Background: Recent studies have found that adropin is associated with coronary artery disease (CAD). This meta-analysis sought to assess the relationship between serum adropin level and CAD. Methods: Online databases including the Cochrane Library, PubMed, EMbase, Ovid, CBM, CNKI, VIP and WanFang Data were electronically searched for the clinical study concerning the relationship between serum adropin levels and CAD, including acute myocardial infarction (AMI), unstable angina pectoris (UAP), and stable angina pectoris (SAP). Two reviewers independently screened literature, extracted data and assessed methodological quality of included studies. Standard mean difference (SMD) with its 95% confidence interval (CI) was used as the effect size in this study. Then meta-analysis was performed using RevMan 5.2 software. Results: A total of seven articles involved 945 participants were included. The results indicated that serum adropin level in CAD group was lower than healthy control group (SMD =−2.44, P=0.0008). In the subgroup analysis, the levels of serum adropin in AMI group (SMD =−2.96, P<0.00001), UAP group (SMD =−2.09, P=0.0001) and SAP group (SMD =−1.23, P=0.007) were also lower than that of healthy control. Conclusions: Serum adropin level in patients with CAD was lower than healthy individuals, indicating that the decrease of adropin concentration might play an important role in the development of CAD.

Reduction in RHR with bisoprolol lowered the incidence of composite cardiac events along with an acceptable safety and tolerability profile.