Estrogen inhibits TGF­ß1­stimulated cardiac fibroblast differentiation and collagen synthesis by promoting Cdc42.

17ß­estradiol (E2) can inhibit cardiac fibrosis in female patients with heart failure (HF) and activate cell division cycle 42 (Cdc42), however it is unknown whether 17ß­estradiol (E2) can ameliorate differentiation and collagen synthesis in TGF­ß1­stimulated mouse cardiac fibroblasts (MCFs) by regulating cell division cycle 42 (Cdc42). The present study aimed to investigate the roles of estrogen and Cdc42 in preventing myocardial fibrosis and the underlying molecular mechanisms. An ELISA was used to measure the levels of E2 and Cdc42 in the serum of patients with heart failure (HF), and western blotting was used to measure the expression levels of Cdc42 in TGF­ß1­stimulated immortalized MCFs. MCFs were transfected with a Cdc42 overexpression (OE) lentivirus or small interfering RNA (siRNA), or treated with a Cdc42 inhibitor (MLS­573151), and the function of Cdc42 was assessed by western blotting, immunofluorescence staining, reverse transcription­quantitative PCR and dual­luciferase reporter assays. Western blotting and immunofluorescence staining were performed to verify the protective effect of E2 on TGF­ß1­stimulated MCFs, and the association between the protective effect and Cdc42. The results demonstrated that Cdc42 levels were increased in the serum of patients with HF and were positively correlated with the levels of E2; however, Cdc42 levels were decreased in TGF­ß1­stimulated MCFs. Cdc42 inhibited MCF differentiation and collagen synthesis, as indicated by the protein expression of α­smooth muscle actin, collagen I and collagen III. Mechanistically, Cdc42 inhibited the transcription of TGF­ß1 by promoting the expression of p21 (RAC1)­activated kinase 1 (Pak1)/JNK/c­Jun signaling pathway proteins and inhibiting the activity of the Tgfb1 gene promoter. In addition, E2 inhibited the differentiation and collagen synthesis of TGF­ß1­stimulated MCFs, and promoted the protein expression of Pak1, JNK and c­Jun, consistent with the effects of Cdc42, whereas the effects of E2 were abolished when Cdc42 was knocked down. The aforementioned findings suggested that E2 could inhibit differentiation and collagen synthesis in TGF­ß1­stimulated MCFs by regulating Cdc42 and the downstream Pak1/JNK/c­Jun signaling pathway.

hAECs and their exosomes improve cardiac function after acute myocardial infarction in rats.

BACKGROUND: Human amniotic epithelial cells (hAECs) are seed cells used to treat acute myocardial infarction (AMI), but their mechanism remains unclear. METHODS: We cultured hAECs and extracted exosomes from culture supernatants. Next, we established a stable AMI model in rats and treated them with hAECs, exosomes, or PBS. We assess cardiac function after treatment by echocardiography. Additionally, heart tissues were collected and analyzed by Masson's trichrome staining. We conducted the tube formation and apoptosis assays to explore the potential mechanisms. RESULTS: Cardiac function was improved, and tissue fibrosis was decreased following implantation of hAECs and their exosomes. Echocardiography showed that the EF and FS were lower in the control group than in the hAEC and exosome groups, and that the LVEDD and LVESD were higher in the control group (P<0.05). Masson's trichrome staining showed that the fibrotic area was larger in the control group. Tube formation was more efficient in the hAEC and exosome groups (P<0.0001). Additionally, the apoptosis rates of myocardial cells in the hAEC and exosome groups were significantly decreased (P<0.0001). CONCLUSIONS: hAECs and their exosomes improved the cardiac function of rats after AMI by promoting angiogenesis and reducing the apoptosis of cardiac myocytes.

Association of serum Cyr61 levels with peripheral arterial disease in subjects with type 2 diabetes.

BACKGROUND: The prevalence of peripheral artery disease (PAD) is obviously increased in patients with diabetes. Existing evidence shows that cysteine-rich angiogenic inducer 61 (Cyr61), a 40-kD secreted protein, plays important roles in regulating cellular physiological processes. Recent studies have demonstrated a significant correlation between serum Cyr61 and atherosclerosis. However, the relationship between Cyr61 levels and PAD in patients with type 2 diabetes (T2DM) remains obscure. METHODS: Data from a total of 306 subjects with T2DM were cross-sectionally analysed. The extent of PAD was determined by using the Fontaine classification, which defines four stages. We measured serum Cyr61 concentrations by ELISA in subjects with and without PAD at Fontaine's stage II, III, or IV. Logistic regression models were used to examine the independent association of Cyr61 with PAD. RESULTS: Out of the 306 subjects enrolled, 150 were free from PAD, while 156 had clinically significant PAD. In subjects with PAD, the prevalences of Fontaine classification stages II, III and IV were 48.7%, 32.1%, and 19.2%, respectively. Patients with more advanced PAD had significantly higher Cyr61 (P for trend < 0.001). The prevalence of PAD on the basis of severity increased with increasing Cyr61 quartiles (all P values for trends < 0.001), and the severity of PAD was positively correlated with Cyr61 quartiles (r = 0.227, P = 0.006). The association of Cyr61 levels with PAD remained after adjusting for major risk factors in a logistic regression analysis. CONCLUSIONS: Our results demonstrated that Cyr61 was significantly increased in PAD patients with T2DM and that Cyr61 levels were positively associated with disease severity. Cyr61 could be a promising biomarker and further studies are needed to assess its clinical utility.

COVID-19 with cystic features on computed tomography: A case report.

RATIONALE: The cystic features of the novel coronavirus disease 2019 (COVID-19) found on computed tomography (CT) have not yet been reported in the published literature. We report the cystic chest CT findings of 2 patients confirmed to have COVID-19-related pneumonia. PATIENT CONCERNS: A 38-year-old man and a 35-year-old man diagnosed with severe COVID-19 pneumonia were admitted to the intensive care unit. DIAGNOSES: Chest CT findings showed multiple cysts in ground-glass opacities (bilaterally) with/without pneumothorax. The cysts had a smooth inner wall. INTERVENTIONS: The patients continued to be given oxygen by mask and received antitussive, phlegm-dispelling treatment. OUTCOMES: At follow up, there was a reduction in the number of multiple cystic lesions on CT. To date, 1 patient was discharged from hospital, while the other had been transferred to the rehabilitation department. LESSONS: COVID-19 may independently result in pulmonary cyst formation and pneumothorax; the application of a ventilator may be another causative factor.

A novel plasma lncRNA ENST00000416361 is upregulated in coronary artery disease and is related to inflammation and lipid metabolism.

Coronary artery disease (CAD) is a serious threat to human health and a major cause of mortality worldwide. Long noncoding RNAs (lncRNAs) affect the occurrence and development of CAD via the regulation of cell proliferation and apoptosis, inflammatory responses and lipid metabolism. Screening methods and therapeutic strategies for CAD have been extensively studied. The present study analyzed clinical indexes of 187 patients with CAD and 150 healthy subjects. The data showed significant differences in diabetes mellitus, hypertension, high­density lipoprotein level and smoking history between the CAD group and the control group. A series of differentially expressed lncRNAs were detected in the plasma samples of three patients with CAD by high­throughput sequencing. Reverse transcription­quantitative (RT­q)PCR data revealed that the expression level of the novel lncRNA ENST00000416361 was ~2.3­fold higher in the plasma of 50 patients with CAD compared with the 50 control subjects. Receiver operating characteristic (ROC) curves were generated, and the area under the ROC curve was 0.7902. Knockdown of ENST00000416361 in human umbilical vein endothelial cells markedly downregulated interleukin­6 and tumor necrosis factor­α levels. In addition, sterol regulatory element binding transcription factor (SREBP)1 and SREBP2 were upregulated in patients with CAD, and they were positively correlated with the expression of ENST00000416361. RT­qPCR further demonstrated that knockdown of ENST00000416361 led to the downregulation of SREBP1 and SREBP2. Overall, the novel lncRNA ENST00000416361 may be associated with CAD­induced inflammation and lipid metabolism, and it may serve as a potential biomarker for CAD.

Fibroblast growth factor 21 inhibits atherosclerosis in apoE-/- mice by ameliorating Fas-mediated apoptosis.

BACKGROUND: FGF21 is a critical endogenous regulator in energy homeostasis and systemic glucose and lipid metabolism. Despite intensive study of the metabolic functions of FGF21, its important role in heart disease needs further exploration. Apoptosis induced by ox-LDL in vascular endothelial cells is an important step in the progress of atherosclerosis. METHODS: The effects of FGF21 treatment on apoptosis induced by ox-LDL were tested in HUVECs. The role of FGF21 in atherosclerosis was studied by evaluating its function in apolipoprotein E double knockout (apoE-/-) mice. RESULTS: We found that apoptosis in HUVECs was alleviated by FGF21 treatment. The effects of FGF21 were independent of the ERK1/2 pathway and were mediated through inhibition of the Fas signaling pathway. FGF21 suppressed the development of atherosclerosis, and the administration of FGF21 ameliorated Fas-mediated apoptosis in apoE-/- mice. CONCLUSION: FGF21 protects against apoptosis in HUVECs by suppressing the expression of Fas; furthermore, FGF21 alleviated atherosclerosis by ameliorating Fas-mediated apoptosis in apoE-/- mice.