Phosphodiesterase 5 (PDE5) inhibition prevents transverse aortic constriction (TAC)-induced cardiac fibrosis by inhibiting transforming growth factor β (TGF-β)-activated Smad signaling. The tissue was stained with Picrosirius Red to detect collagen distribution in the left ventricle. (Courtesy of Dr. Daowen Wang, See Pages 445－455 by Wei Gong et al. for more information.)
Current evidence clearly demonstrates that coronary artery bypass grafting (CABG) remains the “gold standard” treatment for most patients with multivessel and left main stem disease. This article summarizes the relevant evidence basis demonstrating that CABG, in comparison to stenting, reduces mortality and subsequent myocardial infarction and the need for repeat revascularization. The article also describes the evidence basis to support the use of more arterial grafts during CABG and the current role of off-pump CABG.
We review here the novel cardiac protective effects of the multifunctional enzyme, p21-activated kinase 1 (PAK1), a member of a serine/threonine protein kinase family. Despite the large body of evidence from studies in noncardiac tissue indicating that PAK1 activity is key in the regulation of a number of cellular functions, the role of PAK1 in the heart has only been revealed over the past few years. In this review, we assemble an overview of the recent findings on PAK1 signaling in the heart, particularly its cardiac protective effects. We present a model for PAK1 signaling that provides a mechanism for specifically affecting cardiac cellular processes in which regulation of protein phosphorylation states by protein phosphatase 2A (PP2A) predominates. We discuss the anti-adrenergic and antihypertrophic cardiac protective effects of PAK1, as well as its role in maintaining ventricular Ca2+ homeostasis and electrophysiological stability under physiological, β-adrenergic and hypertrophic stress conditions.
microRNAs (miRNAs) are a class of conserved, short, non-coding RNAs that have important and potent capacities to regulate gene expression at the posttranscriptional level. In the past several years, the aberrant expressions of miRNAs in the cardiovascular system have been widely reported, and the crucial roles of some special miRNAs in heart development and pathophysiology of various cardiovascular diseases have been gradually recognized. Recently, it was discovered that miRNAs are presented in peripheral circulation abundantly and stably. This has raised the possibility of using circulating miRNAs as biomarkers for diseases. Furthermore, some studies demonstrated that circulating miRNAs may serve as novel extracellular communicators of cell-cell communication. These discoveries not only reveal the functions of circulating miRNAs in cardiovascular system but also inform the development of miRNAs therapeutic strategies. In this review, we discuss the potential roles of circulating miRNAs in a variety of cardiovascular diseases from biomarkers to therapeutic targets to clearly understand the roles of circulating miRNAs in cardiovascular system.
Aneurysmal dilatation of the aortic sinuses of Valsalva has been most extensively documented in the setting of aortopathies, particularly Marfan syndrome. On the other hand, there is limited data in the literature about congenital sinus of Valsalva aneurysms outside this context. For the purpose of this review, we carried out a literature search on aneurysmal dilatation of the sinuses of Valsalva in Marfan syndrome, and compared this with congenital sinus of Valsalva aneurysms, also including data from a case series from our institution. In conclusion, there are differences in management of aortic dilatation in Marfan syndrome and congenital sinus of Valsalva aneurysms. Though less well-recognised, congenital aneurysms are often associated with significant morbidity and mortality and timely intervention is necessary.
Since first report of aortic root replacement in 1968, the surgical risk and long term outcome of patients with aortic root aneurysm have been continuously improving. In the last 30 years, the surgical approach is also evolving towards more valve conservation with prophylactical intervention at an earlier clinical stage. Translational research has also led to emerging surgical innovation and new drug therapy. Their efficacies are currently under vigorous clinical trials and evaluations.
Stem cells are capable of self-renewal and differentiation, and the processes regulating these events are among the most comprehensively investigated topics in life sciences. In particular, the molecular mechanisms of the self-renewal, proliferation, and differentiation of stem cells have been extensively examined. Multi-omics integrative analysis, such as transcriptomics combined with proteomics, is one of the most promising approaches to the systemic investigation of stem cell biology. We reviewed the available information on stem cells by examining published results using transcriptomic and proteomic characterization of the different stem cell processes. Comprehensive understanding of these important processes can only be achieved using a systemic methodology, and employing such method will strengthen the study on stem cell biology and promote the clinical applications of stem cells.
Recent evidences suggested that cyclic guanosine monophosphate-specific phosphodiesterase 5 (PDE5) inhibitor represents an important therapeutic target for cardiovascular diseases. Whether and how it ameliorates cardiac fibrosis, a major cause of diastolic dysfunction and heart failure, is unknown. The purpose of this study was to investigate the effects of PDE5 inhibitor on cardiac fibrosis. We assessed cardiac fibrosis and pathology in mice subjected to transverse aortic constriction (TAC). Oral sildenafil, a PDE5 inhibitor, was administered in the therapy group. In control mice, 4 weeks of TAC induced significant cardiac dysfunction, cardiac fibrosis, and cardiac fibroblast activation (proliferation and transformation to myofibroblasts). Sildenafil treatment markedly prevented TAC-induced cardiac dysfunction, cardiac fibrosis and cardiac fibroblast activation but did not block TAC-induced transforming growth factor-β1 (TGF-β1) production and phosphorylation of Smad2/3. In isolated cardiac fibroblasts, sildenafil blocked TGF-β1-induced cardiac fibroblast transformation, proliferation and collagen synthesis. Furthermore, we found that sildenafil induced phosphorylated cAMP response element binding protein (CREB) and reduced CREB-binding protein 1 (CBP1) recruitment to Smad transcriptional complexes. PDE5 inhibition prevents cardiac fibrosis by reducing CBP1 recruitment to Smad transcriptional complexes through CREB activation in cardiac fibroblasts.
microRNAs (miRNAs) have played a key role in human tumorigenesis, tumor progression, and metastasis. On the one hand, miRNAs are aberrantly expressed in many types of human cancer; on the other hand, miRNAs can function as tumor suppressors or oncogenes that target many cancer-related genes. This study aimed to investigate the effects of miRNA-200c (miR-200c) on the biological behavior and mechanism of proliferation, migration, and invasion in the prostate cancer cell line Du145. In this study, Du145 cells were transfected with miR-200c mimics or negative control miR-NC by using an X-tremeGENE siRNA transfection reagent. The relative expression of miR-200c was measured by RT-PCR. The proliferation, migration, and invasion abilities of Du145 cells were detected by CCK8 assays, migration assays and invasion assays, respectively. The expressions of ZEB1, E-cadherin, and vimentin were observed by western blot. Results showed that DU145 cells exhibited a high expression of miR-200c compared with immortalized normal prostate epithelial cell RWPE-1. Du145 cells were then transfected with miR-200c mimics and displayed lower abilities of proliferation, migration, and invasion than those transfected with the negative control. The protein levels of ZEB1 and vimentin were expressed at a low extent in Du145 cells, which were transfected with miR-200c mimics; by contrast, E-cadherin was highly expressed. Hence, miR-200c could significantly inhibit the proliferation of the prostate cancer cell line Du145; likewise, miR-200c could inhibit migration and invasion by epithelial-mesenchymal transition.
Approximately one million hysterectomies are performed each year in China. However, national data regarding the indications and the surgical approaches for hysterectomy are lacking. The aim of this study was to examine the surgical indications for hysterectomy in different age groups and the relative merits of different surgical approaches for hysterectomy in Chinese women. Clinical data from 4653 cases of hysterectomy performed in Tongji Hospital from 2004 to 2009 were analysed. Hysterectomy was most commonly performed among women aged 40--49 years (2299; 49.4%). Overall, colporrhagia and abdominal pain were the two most common indications for hysterectomy. The most common indications by age groups were as follows: malignant ovarian tumour,<20 years; malignant uterine tumour, 20--29 and 30--39 years; uterine myoma, 40--49 and 50--59 years; and uterine prolapse, 60--69 and>70 years. The proportion of malignant aetiology also varied by age, being the highest in women aged<20 years (75.0%) and the lowest in those aged 40--49 years (19.9%). Approximately 35% women who had hysterectomies also had concomitant bilateral oophorectomy. The lowest rate of oophorectomy occurred in women aged 30--39 years (15.8%), whereas the highest rate was in those aged 50--59 years (75.9%). The abdominal surgical approach was used in 84% of all hysterectomies. Surgeries using the vaginal approach required a significantly shorter operating time (118 min average) than all other approaches (P<0.05). Both the amount of bleeding and the blood transfusion volume required were smaller in vaginal approaches, with no significant differences between the others. The surgical approaches used were also related to the scope of surgery. Both the surgical indications and the rates of bilateral oophorectomy varied by age. In terms of both operating time and the amount of bleeding and blood transfusion volume required, the vaginal approach was superior to all other surgical approaches.
This work aims to estimate the value of diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI) in detecting early-stage kidney injury in type 2 diabetic patients with normoalbuminuria (NAU) versus microalbuminuria (MAU) prospectively. A total of 30 T2DM patients with normal kidney function were recruited and assigned to the NAU group (n = 14) or MAU group (n = 16) according to 8 h overnight urinary albuminuria excretion rate (AER) results. A contemporary cohort of health check-up recipients were included as controls (n = 12). DWI and DTI scans were performed on bilateral kidney using SE single-shot EPI, and apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of the renal parenchyma was determined from ADC and FA maps of the three groups. ADC and FA values were compared among the three groups. According to DWI with a b value of 400 s/mm2, the MAU and NAU groups showed significantly lowered mean ADC values compared with the healthy controls (P<0.01). The mean ADC in the MAU group [(2.22±0.07)×10–3 mm2/s] was slightly lower than that of the NAU group [(2.31±0.22)×10–3 mm2/s], but this difference was not statistically significant (P>0.05). The FA value in the MAU group was higher than that in the control group (0.45±0.07 vs. 0.39±0.03, P = 0.004) but did not differ from that in the NAU group (0.42±0.03) (P>0.05). ADC and FA values may be more sensitive than urine AER in reflecting early-stage kidney injury and, hence, may facilitate earlier detection and quantitative evaluation of kidney injury in T2DM patients. Combined evaluation of ADC and FA values may provide a better quantitative approach for identifying diabetic nephropathy at early disease stages.
The association between dyslipidemia and elevated fasting glucose in type 2 diabetes is well known. In non-diabetes, whether this association still exists, and whether dyslipidemia is an independent risk factor for high fasting plasma glucose (FPG) levels are not clear. This cross-sectional study recruited 3460 non-diabetic Chinese subjects (1027 men, and 2433 women, aged 35–75 years old) who participated in a health survey. Men and women were classified into tertiles by levels of plasma lipids respectively. In women, the prevalence of impaired fasting glucose (IFG) was decreased with increased HDL-C. A stepwise increase in HDL-C was associated with decreasing FPG levels (lowest tertiles, FPG: 5.376±0.018; middle tertiles, 5.324±0.018; highest tertiles, 5.276±0.018 mmol/L; P=0.001). Reversely, FPG levels increased from lowest tertiles to highest tertiles of LDL-C, TC, and TG. we found that women in the first tertile with lower HDL-C level had a 1.75-fold increase in risk of IFG compared with non-diabetic women in the third tertile with higher HDL-C level (OR: 1.75; 95% CI: 1.20--2.56). In men, no significant association was found. We took age, BMI, waist/hip ratio, education, smoking, alcohol drinking, and physical exercise as adjusted variables. In Chinese non-diabetic women, dyslipidemia is independently associated with high levels of FPG; TG, HDL-C, and LDL-C are predictors of IFG independent of BMI and waist/hip ratio.
Paratesticular fibrous pseudotumor is a rare benign tumor that originates from intrascrotal tissue, such as tunica vaginalis, epididymis, or spermatic cord. Five cases of fibrous pseudotumor in our hospital were reviewed retrospectively, and the clinical manifestations were analyzed. Three cases of unilateral nodules, comprising one case located in the tunica vaginalis and two cases located in the epididymis, underwent local excision of the unilateral nodule. Two cases of diffuse incrassation in the tunica vaginalis underwent right radical orchiectomy. Postoperative pathological examination showed that all were fibrous pseudotumors. An average follow-up of 26 months showed uneventful results without recurrence for all patients. Fibrous pseudotumor is not a neoplasm but a reactive fibrous inflammatory hyperplasia. Definitive diagnosis requires pathological examination. Radical orchiectomy should be avoided when possible, and local excision should be performed because of the lack of obvious evidence of potential malignancy.