HDAC1-Mediated Downregulation of NEU1 Exacerbates the Aggressiveness of Cervical Cancer.

HDAC1 functions as an oncogene in multi-type cancers. This study aimed to investigate the roles of histone deacetylase 1 (HDAC1) in cervical cancer (CC). mRNA expression was determined using reverse transcription quantitative polymerase chain reaction. The protein-protein complexes was analyzed using co-immunoprecipitation assay. The binding sites between NRF2 and NEU1 were confirmed by chromatin immunoprecipitation assay. Cell viability was detected by CCK-8. Cell proliferation was measured using CCK-8 and colony formation assays. Cell migrative and invasive ability were determined using transwell assay. We found that HDAC1 was upregulated in CC patients and cells. Trichostatin A (TSA) treatment decreased the number of colonies and migrated and invaded cells. Moreover, HDAC1 interacted with NRF2 to downregulate NEU1 expression. NEU1 knockdown attenuated the effects of TSA and enhanced the aggressiveness of CC cells. In conclusion, HDAC1 functions as an oncogene in CC. Targeting HDAC1 may be an alternative strategy for CC.

miR-129-5p/FGF2 axis is associated with homocysteine-induced human umbilical vein endothelial cell injury.

PURPOSE: Homocysteine (Hcy)-induced endothelial cell injury is a key event in atherosclerosis pathogenesis. In this study, we aimed to explore the mechanisms underlying Hcy-induced endothelial injury by assessing the effects of Hcy on endothelial cell proliferation and the microRNA (miR)-129-5p/fibroblast growth factor 2 (FGF2) axis. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with Hcy to construct an endothelial cell injury model. Expression levels of FGF2 in Hcy-induced HUVECs were determined using quantitative real-time polymerase chain reaction and western blotting. An FGF2 overexpression lentiviral vector was constructed to upregulate FGF2 expression in HUVECs via lentivirus transduction. A cell counting kit-8 assay was used to explore the effects of FGF2 overexpression on HUVEC proliferation. An upstream regulatory miRNA was predicted, and its target-binding relationship with FGF2 was evaluated using a dual-luciferase reporter assay. RESULTS: We found that FGF2 expression in HUVECs was inhibited by Hcy treatment. Lentivirus transduction led to the overexpression of FGF2 in HUVECs, which significantly reversed the effect of Hcy on endothelial cell proliferation. miR-129-5p was experimentally validated as an upstream regulator of FGF2, and its decreased levels in HUVECs led to increased FGF2 expression. In addition, HUVEC proliferation was enhanced by the knockdown of miR-129-5p, and this effect was reversed by Hcy treatment. CONCLUSION: Taken together, the results of this study revealed that Hcy inhibits FGF2 expression in HUVECs, and FGF2 is regulated by upstream miR-129-5p to improve the effect of Hcy on endothelial cell proliferation.

The pathology, phylogeny, and epidemiology of Echinococcus ortleppi (G5 genotype): a new case report of echinococcosis in China.

BACKGROUND: Cystic echinococcosis (CE), caused by the larval stage of the complex Echinococcus granulosus sensu lato (s.l.), is a zoonotic parasitic disease with a high social burden in China. E. ortleppi is a species (formerly genotype 5 of E. granulosus s.l.) with unique epidemic areas (tropical areas), transmission patterns (mainly cattle origin), and pathological characteristics (large and small hook lengths) compared to other species that cause CE. A 19-year-old female patient in an area with no history of echinococcosis in Guizhou Province, China, was diagnosed with E. ortleppi infection in 2019. This study is to understand the source of this human E. ortleppi infection. METHODS: We performed computer tomography (CT) scans, surgical operation, morphological sectioning, molecular diagnosis, phylogenetic analyses, and epidemiological investigation in Anshun City, Guizhou Province, China in 2019. RESULTS: The patient presented with intermittent distension and pain in the upper abdomen without other abnormal symptoms. Routine blood examination results were normal. However, abdominal CT revealed a fertile cyst with a diameter of approximately 8 cm, uniform density, and a clear boundary, but without an evident cyst wall in the right lobe of the liver. The cyst was fertile, and phylogenetic analyses revealed that the isolates represented a new E. ortleppi genus haplotype. A result of 10‒14 years incubation period with indigenous infection was considered available for the case through the epidemiological survey. CONCLUSIONS: CE due to E. ortleppi infection can be confused with other diseases causing liver cysts, resulting in misdiagnosis. A transmission chain of E. ortleppi may exist or existed in the past in the previously considered non-endemic areas of echinococcosis in southwestern China.

Bioinformatics-based analysis of the involvement of AC005550.3, RP11-415D17.3, and RP1-140K8.5 in homocysteine-induced vascular endothelial injury.

This study aimed to explore the role of certain genes and long non-coding RNAs (lncRNAs) in homocysteine (HCY)-induced vascular endothelial injury. HUVECs were treated with HCY, then cell cycle and apoptosis were analyzed by flow cytometry. HUVECs were then sequenced and analyzed using bioinformatics, with a focus on differentially expressed genes/lncRNA (DEGs/DEL), protein-protein interaction (PPI), functional enrichment analyses, and lncRNA-target prediction. Although HCY did not affect the cell cycle, it significantly increased the number of apoptotic cells. In total, 382 DEGs and 147 DELs were identified; DEGs such as CD34, FGF2, and SERPINE1 were the hub nodes in the PPI network, in addition to being the targets of AC005550.3, RP11-415D17.3, and RP1-140K8.5, respectively. Functional enrichment analysis showed that the targets of downregulated AC005550.3 and RP11-415D17.3 were significantly enriched in blood vessel development and those of upregulated RP1-140K8.5 were enriched in fibrinolysis. RT-qPCR showed that the mRNA levels of AC005550.3, RP11-415D17.3, and RP1-140K8.5 were consistent with the results predicted by our bioinformatics analysis. In conclusion, downregulated AC005550.3 and RP11-415D17.3 targeting CD34 and FGF2 and upregulated RP1-140K8.5 targeting SERPINE1 may play an important role in HCY-induced vascular endothelial injury by regulating blood vessel development and fibrinolysis, respectively.

Leptin is associated with heart rate recovery in Chinese hypertensive patients.

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 (ß = -0.268, P < 0.01). Serum leptin remained negatively associated with HRR (ß = -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.

Curcumin protects endothelial cells against homocysteine induced injury through inhibiting inflammation.

OBJECTIVE: This study aimed to investigate the protective effects of curcumin on the homocysteine (HCY) induced injury to the endothelial cells. METHODS: Endothelial cells were treated with HCY at different concentrations, and MTT assay was employed to determine an optimal concentration of HCY. Cells were divided into 3 groups: normal control group, HCY group and HCY + curcumin group. In curcumin group, cells were pretreated with 2.5 mmol/L HCY for 2 h and then incubated with curcumin at different concentrations. MTT assay was employed to detect the cell viability. ELISA was performed to detect the content of IL-8 in the supernatant. Western blotting was used to detect NF-κB expression in cells. RESULTS: (1) Endothelial cells were polygonal or stone-like, or aggregated to form masses, and then gradually became long spindle shaped, cell body enlarged, cells were rich in cytoplasm, and immunohistochemistry for factor VIII showed positive. (2) MTT assay showed HCY at ≥2.5 mmol/L caused significant damage to endothelial cells as compared to control group. Thus, 2.5 mmol/L HCY was used in following experiments. (3) ELISA showed IL-8 in the supernatant increased significantly in a time dependent manner after HCY treatment (P<0.01), but curcumin could significantly inhibit the IL-8 secretion in endothelial cells after HCY treatment. (4) Western blotting showed HCY was able to markedly increase NF-κB expression, which, however, was significantly inhibited by curcumin. CONCLUSION: Curcumin is able to protect the endothelial cells against HCY induced injury through inhibiting NF-κB activation and down-regulating IL-8 expression.

Implantation of placenta-derived mesenchymal stem cells accelerates murine dermal wound closure through immunomodulation.

BACKGROUND: Diabetic foot ulcer (DFU) is a major complication of diabetes mellitus. Although previous studies have established that inflammation, ischemia and neuropathy contribute to the development of DFU, it is still an unmet medical need due to lack knowledge of cellular and molecular mechanisms associated with DFU. In the present study, we tested our hypothesis that subcutaneous application of human placental mesenchymal stem cells (PMSCs) can accelerate diabetic dermal wound healing by modulating immunoresponse. METHODS AND RESULTS: By using an in vivo excisional wound healing model in Goto-Kakizaki (GK) rats, we found that injection of PMSCs accelerates wound closure. Further studies revealed that application of PMSCs can regulate inflammation associated with wound healing by controlling secretion of pro- and anti-inflammatory factors, the beneficial effects can be partially blocked by application of antibodies against interleukin-10 (IL-10). Furthermore, in vitro experiments suggested that co-culture of PMSCs with human dermal fibroblasts can significantly inhibit activation of NF-ĸB induced by lipopolysaccharides (LPS), indicating the molecular mechanism of PMSCs mediated immunomodulation. CONCLUSION: Taken together, our study suggested that the immunomodulation of PMSCs play an important role on diabetic dermal wound healing process, thus PMSCs might represent an attractive choice for treatment of diabetes dermal wound and DFU.

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 AND 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-kB 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.

Genomic expression profiling and bioinformatics analysis on diabetic nephrology with ginsenoside Rg3.

Diabetic nephropathy (DN), a common diabetes-related complication, is the leading cause of progressive chronic kidney disease (CKD) and end­stage renal disease. Despite the rapid development in the treatment of DN, currently available therapies used in early DN cannot prevent progressive CKD. The exact pathogenic mechanisms and the molecular events underlying DN development remain unclear. Ginsenoside Rg3 is a herbal medicine with numerous pharmacological effects. To gain a greater understanding of the molecular mechanism and signaling pathway underlying the effect of ginsenoside Rg3 in DN therapy, an RNA sequencing approach was performed to screen differential gene expression in a rat model of DN treated with ginsenoside Rg3. A combined bioinformatics analysis was then conducted to obtain insights into the underlying molecular mechanisms of the disease development, in order to identify potential novel targets for the treatment of DN. Six Sprague­Dawley male rats were randomly divided into 3 groups: Normal control group, DN group and ginsenoside­Rg3 treatment group, with two rats in each group. RNA sequencing was adopted for transcriptome profiling of cells from the renal cortex of DN rat model. Differentially expressed genes were screened out. Cluster analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to analyze the differentially expressed genes. In total, 78 differentially expressed genes in the DN control group were identified when compared with the normal control group, of which 52 genes were upregulated and 26 genes were downregulated. Differential expression of 43 genes was observed in the ginsenoside­Rg3 treatment group when compared with the DN control group, consisting of 10 upregulated genes and 33 downregulated genes. Notably, 21 that were downregulated in the DN control group compared with the control were then shown to be upregulated in the ginsenoside­Rg3 treatment group compared with the DN control group. In addition, 7 upregulated genes in the DN control group compared with the control were then shown to be downregulated in the ginsenoside­Rg3 treatment group compared with the DN control group. Cluster analysis based on differentially expressed genes indicated that the transcriptomes are quite different among the samples. Distinct GO terms associated with these groups of genes were shown to be enriched. KEGG pathway analysis demonstrated that differentially expressed genes were predominantly involved in the fatty acid metabolism pathway and peroxisome proliferator­activated receptor (PPAR) signaling pathway. To the best of our knowledge, this study was the first to present whole genome expression profiling in DN with ginsenoside­Rg3 treatment by RNA­Seq. A set of differentially expressed genes and pathways were identified. These data provided an insight into understanding the molecular mechanisms underlying the effect of ginsenoside­Rg3 treatment of DN.

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.

Effects of 4 month exercise on left ventricular remodeling and autonomic nervous system in hypertensive patients.

BACKGROUND: We sought to investigate effects of supervised exercise training on left ventricular remodeling, left ventricular function and autonomic nervous system of hypertensive patients without medication. METHODS: Fifty borderline and mildly hypertensive patients were enrolled and randomly divided into 2 groups (25 in each). Exercise group received a 4 months' exercise program, prescribed according to their first cardiopulmonary exercise tests, while the control group received routine dietary recommendation. All patients underwent noradrenalin assay, cardiopulmonary exercise tests and echocardiographic studies at enrollment and 4 month follow-up. RESULTS: At baseline no statistically difference between the two groups were observed in clinical characteristics, echographic variants or cardiopulmonary test index. Four months later, exercise group showed higher values of VO2peak, Powermax (max workload), AT (anaerobic threshold), VO2AT (VO2 at anaerobic threshold), tAT (time from beginning to anaerobic threshold) and heart rate recovery compared to the control group (P<0.05). Additionally, systolic/diastolic blood pressure decreased significantly in the exercise group compared to the control group (P<0.05). Moreover, there was significant reduction in left ventricular mass index in the exercise group (P<0.01), and there was also an inverse correlation between changes in left ventricular mass index and heart rate recovery (r=-0.52, P<0.01). CONCLUSIONS: Four-month exercise training in borderline and mildly hypertensive patients not only decreased their blood pressure levels, but also induced an improvement of exercise capability, left ventricular remodeling and heart rate recovery. Heart rate recovery improvement was significantly associated with decrease of left ventricular mass index, which indicated that favorable adjustment in autonomic nervous system of exercise training might be an important pathway to reverse left ventricular remodeling.

Akt/eNOS signaling pathway mediates inhibition of endothelial progenitor cells by palmitate-induced ceramide.

Palmitate (PA) impairs endothelial progenitor cells (EPCs). However, the molecular mechanism underlying the suppressive function of PA remains largely unknown. Ceramide, a free fatty acid metabolite, mediates multiple cellular signals. We hypothesized that ceramide acts as an intermediate molecule to mediate inhibition of EPCs by PA. We first demonstrated that PA could inhibit the attachment, migration, and tube formation of EPCs through suppression of the Akt/endothelial nitric oxide (NO) synthase (eNOS) signaling pathway. In addition, we observed that PA could induce ceramide accumulation in EPCs. To test whether the accumulation of ceramide causes EPC dysfunction, the ceramide synthesis inhibitors myriocin and fumonisin B1 were used. We that found both inhibitors could effectively abolish PA-mediated EPC inhibition. Furthermore, the ceramide deacylation inhibitor N-oleoylethanolamine could augment the inhibitory effect of PA on EPCs, indicating that it is ceramide, not its metabolites, that mediates the suppression of EPCs by PA. We have previously shown that Akt/eNOS phosphorylation was reduced after PA treatment, which, in turn, hampered the normal bioavailability of NO, leading to impaired functions of EPCs. To test the role for ceramide in this process, a clinically used NO donor, sodium nitroprusside, was used. We found that sodium nitroprusside could rescue the suppressive effects of ceramide on EPCs, suggesting that ceramide-mediated EPC inhibition might be through reduction of NO production. Taken together, our findings indicated that ceramide-induced reduction of NO might be the molecular mechanism for PA-mediated EPC inhibition; thus, targeting either ceramide or NO production might be an effective means for improvement of EPC functions in diseases.

Association of soluble receptor for advanced glycation end products levels with hypertensive albuminuria.

OBJECTIVE: Soluble receptor for advanced glycation end products (sRAGE) levels have been found to be decreased in chronic inflammatory diseases including atherosclerosis, hypertension and renal failure. This study evaluated the relationship between sRAGE concentrations and urinary albumin excretion in patients with essential hypertension. METHODS: A total of 200 consecutive patients with essential hypertension were enrolled and were divided into 3 groups. RESULTS: Plasma sRAGE levels were significantly lower in hypertensive patients with micro- or macroalbuminuria compared with those in hypertensive patients with normoalbuminuria, and the values in the macroalbuminuria group were even lower than in the microalbuminuria group (128.6±24.2, 244.6±37.6±313.6±30.7 pg/ml, respectively). In addition, plasma sRAGE level was an independent determinant of log urinary albumin excretion in patients with essential hypertension (ß=-0.267, P<0.05). CONCLUSIONS: sRAGE may play a role in the pathogenic processes that link albuminuria, chronic inflammation and oxidative stress in hypertensive patients.

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

BACKGROUND: Left 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. RESULTS: After 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). CONCLUSIONS: TB 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.

Stromal cell-derived factor-1α attenuates oleate-induced acute lung injury in rabbits.

The stromal cell-derived factor-1α/C-X-C chemokine receptor 4 (SDF-1/CXCR4) axis is involved in various aspects of tissue repair, regeneration and development. However, the role of SDF-1/CXCR4 in acute lung injury (ALI) remains largely unknown. The aim of the present investigation is to examine pathological changes in a rabbit model with ALI induced by oleic acid (OA) and to explore the protective effect of SDF-1α on ALI. Intravenous application (i.v.) of oleic acid (0.1 ml/kg/h for 2h) provoked pulmonary hemorrhage, edema, and protein leakage, resulting in severe ALI. When the rabbit received an infusion of SDF-1α (20 µg/kg/24h) for 30 min before OA treatment, SDF-1α seemed to significantly improve the pathologies associated with OA-induced ALI. While dissecting the molecular mechanisms underlying the beneficial effects of SDF-1α, we found that SDF-1/CXCR4 is expressed in uninjured lung tissues but is greatly reduced after OA treatment. Interestingly, intravenous delivery of SDF-1α could target an injured lung and rescue expression of CXCR4, which in turn activates anti-apoptotic proteins, Bcl-1 and Bcl-xl, but does not affect pro-apoptotic proteins, such as Bad and Bax. These data suggested that SDF-1α could protect rabbit lungs from AIL. The molecular mechanism might be associated with upregulating anti-apoptosis family expression through CXCR4. Thus, SDF-1/CXCR4 signaling pathway may be a promising target for treatment of patients with ALI.

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.

Echocardiographic assessment of hypertensive patients with or without hyperhomocysteinemia.

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/m(2)), 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. 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.

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

BACKGROUND: Left 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. RESULTS: After 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). CONCLUSIONS: TB 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.

Association between polymorphism of the G-protein ß3 subunit C825T and essential hypertension: an updated meta-analysis involving 36,802 subjects.

PURPOSE: The G-protein ß3-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). Begg's 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.