Nanzi Xie

Transplantation of placenta-derived mesenchymal stem cells enhances angiogenesis after ischemic limb injury in mice

Mesenchymal stem cell‐based therapy has emerged as a promising approach for the treatment of peripheral arterial disease. The purpose of this study was to examine the potential effects of human placenta‐derived mesenchymal stem cells (PMSCs) on mouse hindlimb ischemia. PMSCs were isolated from human placenta tissue and characterized by flow cytometry. An in vivo surgical ligation‐induced murine limb ischemia model was generated with fluorescent dye (CM‐DiI) labelled PMSCs delivered via intramuscular injection. Our data show that PMSCs treatment significantly enhanced microvessel density, improved blood perfusion and diminished pathologies in ischemic mouse hindlimbs as compared to those in the control group. Further immunostaining studies suggested that injected PMSCs can incorporate into the vasculature and differentiate into endothelial and smooth muscle cells to enhance angiogenesis in ischemic hind limbs. This may in part explain the beneficial effects of PMSCs treatment. Taken together, we found that PMSCs treatment might be an effective treatment modality for treatment of ischemia‐induced injury to mouse hind limbs by enhancement of angiogenesis.

Association between polymorphism of the G-protein β3 subunit C825T and essential hypertension: an updated meta-analysis involving 36,802 subjects.

PURPOSE The G-protein β3-subunit gene C825T polymorphism (GNB3-C825T) has been reported to be associated with essential hypertension (EH), but results from previous studies are conflicting. The present study aimed at investigating the association between this polymorphism and risk of EH using a meta-analysis on the published studies. MATERIALS AND METHODS PubMed, Embase, CBM (China Biological Medicine Database), Wanfang and VIP databases were searched to identify eligible studies published in English and Chinese before March 2013. Data were extracted using standardized methods. The association was assessed by the odds ratio (OR) with 95% confidence intervals (CI). Beggs test was used to measure publication bias. RESULTS A total of 40 case-control studies containing 16,518 EH patients and 20,284 controls were involved in this meta-analysis. Overall, a significant association was found between GNB3 C825T polymorphism and risk of EH when all studies were pooled with a random-effects model for T versus C (OR=1.09, 95% CI: 1.04-1.19). In the subgroup analysis, the same association was found in overall Caucasian (T versus C, OR=1.16, 95% CI 1.08-1.24) and Chinese populations (TT versus CC, OR=1.23, 95% CI 1.06-1.57). No associations were detected between GNB3-C825T and the risk of EH overall in Asian and Japanese people. CONCLUSIONS Meta-analysis results suggest that the GNB3-C825T polymorphism is associated with risk of EH in the overall population, the Caucasians and the Chinese. The effect of the variants on the expression levels and the possible functional role of the variants in EH should be addressed in further studies.

Delivery of placenta-derived mesenchymal stem cells ameliorates ischemia induced limb injury by immunomodulation.

Background: Peripheral artery disease (PAD) is a major health burden in the world. Stem cell-based therapy has emerged as an attractive treatment option in regenerative medicine. In this study, we sought to test the hypothesis that stem cell-based therapy can ameliorate ischemia induced limb injury. Methods: We isolated mesenchymal stem cells derived from human placentas (PMSCs) and intramuscularly transplanted them into injured hind limbs. Treatment with PMSCs reduced acute muscle fibers apoptosis induced by ischemia. Results: PMSC treatment significantly enhanced regeneration of the injured hind limb by reducing fibrosis and enhancing running capacity when the animals were subjected to treadmill training. Mechanistically, injected PMSCs can modulate acute inflammatory responses by reducing neutrophil and macrophage infiltration following limb ischemia. ELISA assays further confirmed that PMSC treatment can also reduce pro-inflammatory cytokines, TNF-α and IL-6, and enhance anti-inflammatory cytokine, IL-10 at the injury sites. Conclusion: Taken together, our results demonstrated that PMSCs can be a potential effective therapy for treatment of PAD via immunomodulation.

Association of serum total bilirubin levels with diastolic dysfunction in heart failure with preserved ejection fraction

BackgroundLeft ventricular diastolic dysfunction is one of the main characteristics of heart failure patients with a preserved left ventricular ejection fraction. As bilirubin is regarded as an important endogenous antioxidant molecule, serum total bilirubin levels were compared between heart failure patients with a preserved left ventricular ejection fraction and normal controls in this study. We recruited 327 heart failure patients with a preserved left ventricular ejection fraction and 200 healthy controls. Patients were divided into 4 subgroups by their comprehensive echocardiographic manifestations, 1-mild, 2-moderate, 3-severe (reversible restrictive), 4-severe (fixed restrictive). Total bilirubin levels were compared using stepwise multiple regressions adjusted for selected factors.ResultsAfter adjusting for gender, age, smoking, systolic blood pressure, diastolic blood pressure, total cholesterol and triglyceride, serum total bilirubin levels were significantly lower in the heart failure group compared with the control group (P < 0.01). Patients in the subgroup (4-severe) showed significantly (P < 0.05) lower levels of total bilirubin when compared with the subgroup (1-mild).ConclusionsTB level was negatively correlated with left ventricular diastolic dysfunction in heart failure patients with a preserved left ventricular ejection fraction, which might provide a new insight into the complicated mechanisms of heart failure with a preserved left ventricular ejection fraction.

Echocardiographic assessment of hypertensive patients with or without hyperhomocysteinemia

Abstract The study was designed to assess left ventricular (LV) systolic and diastolic function in hypertensive patients with or without Hhcy. The study participants consisted of 40 hypertensive patients with Hhcy, 40 hypertensive patients without Hhcy and 40 age-matched healthy control participants. Cardiac functions were determined using echocardiography and the Tei index was calculated for analysis. LAVI (left atrial volume index), IVST (interventricular septum thickness in diastole), PVST (posterior ventricular septum thickness in diastole), LVMI (left ventricular mass index), E/A (peak early and late diastolic transmitral filling flow velocities ratio), DT (deceleration time of the E wave), IRT (isovolumic relaxation time), and the Tei index were different in the hypertensive patient groups (hypertension with Hhcy and hypertension without Hhcy) compared with the controls. The Tei index was significantly higher in the hypertensive groups compared with the controls (0.62 ± 0.05, 0.51 ± 0.04, and 0.40 ± 0.04, respectively, p < 0.01). Significant differences were also observed between the hypertensive patients with Hhcy and the hypertensive patients without Hhcy regarding LAVI (25.6 ± 4.7 versus 22.9 ± 3.5 ml/m2), E/A (0.73 ± 0.22 versus 0.92 ± 0.14), DT (93.1 ± 6.9 versus 84.3 ± 8.1 ms), IRT (93.1 ± 6.9 versus 84.3 ± 8.1 ms) and the Tei index. Significant correlations were observed between serum homocysteine levels and LV diastolic function parameters (LAVI: r = 0.39, E/A: r = −0.32, DT: r = 0.47, IRT: r = 0.51, p < 0.05). We found that Hhcy had contributory effects on myocardial impairment induced by hypertension. Moreover, there were strong relationships between homocysteine level and LV diastolic dysfunction parameters.

Curcumin Ameliorates Ischemia-Induced Limb Injury Through Immunomodulation.

Background The prevalence of peripheral arterial disease (PAD) is increasing worldwide. Currently, there is no effective treatment for PAD. Curcumin is an ingredient of turmeric that has antioxidant, anti-inflammation, and anticancer properties. In the present study we investigated the potential effect of curcumin in protecting against ischemic limb injury. Material/Methods We used an established hindlimb ischemia mouse model in our study. Curcumin was administrated through intraperitoneal (I.P.) injection. Immunohistochemical staining and ELISA assays were performed. Treadmill training was used to evaluate skeletal muscle functions of animals. Results Our experiments using in vivo treadmill training showed that curcumin treatment improved the running capacity of animals after ischemic injury. Histological analysis revealed that curcumin treatment significantly reduced the skeletal muscle damage and fibrosis associated with ischemic injury. In order to determine the cellular and molecular mechanisms underlying curcumin-mediated tissue protection, immunohistochemical staining and ELISA assays were performed. The results showed that curcumin treatment led to less macrophage infiltration and less local inflammatory responses as demonstrated by decreasing TNF-α, IL-1, and IL-6 levels. Further immunofluorescent staining of tissue slides indicated that curcumin treatment inhibited the NF-κB signaling pathway. Finally, curcumin can inhibit NF-κB activation induced by LPS in macrophages. Conclusions Our study results show that curcumin treatment can ameliorate hindlimb injury following ischemic surgery, which suggests that curcumin could be used for PAD treatment.

Leptin is associated with heart rate recovery in Chinese hypertensive patients

ABSTRACT Elevated serum leptin concentrations are closely related to sympathetic nervous system activation in essential hypertension (EH); however, it is not clear whether or not they are associated with parasympathetic nervous system impairment in EH. Heart rate recovery (HRR) is a reproducible method used to assess parasympathetic activity. This study aimed to investigate the relationship between serum leptin and HRR in Chinese untreated EH patients. This was a cross-sectional study enrolling 471 Chinese EH patients (205 men, 266 women; mean age 63.1 years). HRR was calculated during an incremental cardiopulmonary exercise test. Simple and multiple regression analyses were used to assess the correlation between serum leptin level and HRR value. Serum leptin levels elevated with increasing BP values. Moreover, univariate analysis revealed that the HRR value was negatively correlated with serum leptin (r = −0.037, P < 0.01). In multiple regression analysis, the age-adjusted serum leptin level was negatively correlated with HRR (β = −0.268, P < 0.01). Serum leptin remained negatively associated with HRR (β = −0.017, P < 0.01) after further adjustments for factors including age, systolic blood pressure, total cholesterol, and several factors that correlated with HRR. Our findings demonstrated that a raised serum leptin concentration is related to HRR blunt, which suggests that the role of leptin in the development of EH might be associated with impairment of the parasympathetic nervous system as well.

Sphingomyelin levels in nondipper and dipper hypertensive patients

A number of studies have focused on the association between sphingomyelin (SM) levels and atherosclerosis, however, there are few data concerning the correlation of SM with nondipper hypertension. The present study aimed to investigate the correlation between plasma SM levels and nondipper status in patients with hypertension. A total of 200 hypertensive patients were enrolled and divided into two groups according to their ambulatory blood pressure monitoring (AMBP) results: Dipper group (84 patients) and nondipper group (116 patients). All patients were subjected to transthoracic echocardiography examination and laboratory tests. No statistically significant difference was observed between the two groups in terms of basic clinical characteristics. However, the plasma SM levels in the dipper group were significantly lower than those of the nondipper group (41.9±17.5 vs. 96.4±14.3 mg/dl, P=0.003). The left ventricular mass index (LVMI) was higher in the nondipper patients than in the dipper patients and the diastolic function parameters in the nondipper patients were less favorable. Correlation analysis showed that the SM level was negatively correlated with the magnitude of systolic blood pressure (SBP) fall at night (r=−0.42, P<0.01) and diastolic blood pressure (DBP) fall at night (r=−0.31, P<0.01). The nondipper status had contributory effects on hypertensive concentric hypertrophy and diastolic function impairment. In addition, the plasma SM level was associated with a nondipper pattern of hypertension.