Ablation index-guided ablation with milder targets for atrial fibrillation: Comparison between high power and low power ablation.

Background: High power-ablation index (HP-AI)-guided ablation for atrial fibrillation (AF) targeting high AIs has been implemented in European countries. However, milder AI targets are widely used in Asia. The safety and efficacy of HP-AI-guided ablation compared with those of low-power AI-guided ablation in a milder AI-targeting setting are unknown. The goal of this study was to explore the efficacy and safety of HP-AI-guided ablation in a milder AI-targeting setting. Methods: Patients who underwent pulmonary vein isolation (PVI) for AI-guided atrial fibrillation ablation in our center were enrolled and divided into 2 groups according to the ablation power used. In the HP-AI group, the ablation power was over 45 W, while the low power-AI group was ablated with <35 W power. The targeted AIs were 450-500 in the anterior wall and 350-400 in the posterior wall. The efficacy outcome was expressed as the single-procedure atrial arrhythmia-free survival between 91 days and 1 year. Safety outcomes included severe adverse events (SAEs), including symptomatic pulmonary vein (PV) stenosis, atrioesophagal fistula, cardiac tamponade, stroke, thromboembolism events, myocardial infarction, and major bleeding. Results: A total of 134 patients were enrolled, of whom 74 underwent PVI using HP-AI, while 60 received low power-AI ablation. After a mean follow-up time of 7.4 months, 22 (16.4%) patients showed arrhythmia recurrence: 5 (6.8%) patients in the HP-AI group and 17 (28.3%) patients in the low power-AI group. The HP-AI group showed a significantly higher arrhythmia-free survival than the low power-AI group (p = 0.011). Two patients in the low power-AI group and 1 patient in the HP-AI group developed an SAE (p = NS). Compared with the low power-AI group, the HP-AI group demonstrated a higher PV first-pass isolation rate, shorter ablation time, and fewer patients with anatomical leakages and sites of unreached AI. Conclusion: In a milder AI setting, HP-AI ablation might result in significantly higher arrhythmia-free survival than low power-AI ablation and a similar safety profile.

Stem cells from a malignant rat prostate cell line generate prostate cancers in vivo: a model for prostate cancer stem cell propagated tumor growth.

Cancer stem cells (CSCs) are resistant to conventional cancer therapies, permitting the repopulation of new tumor growth and driving disease progression. Models for testing prostate CSC-propagated tumor growth are presently limited yet necessary for therapeutic advancement. Utilizing the congenic nontumorigenic NRP152 and tumorigenic NRP154 rat prostate epithelial cell lines, the present study investigated the self-renewal, differentiation, and regenerative abilities of prostate stem/progenitor cells and developed a CSC-based PCa model. NRP154 cells expressed reduced levels of tumor suppressor caveolin-1 and increased p-Src as compared to NRP152 cells. Gene knockdown of caveolin-1 in NRP152 cells upregulated p-Src, implicating their role as potential oncogenic mediators in NRP154 cells. A FACS-based Hoechst exclusion assay revealed a side population of stem-like cells (0.1%) in both NRP152 and NRP154 cell lines. Using a 3D Matrigel culture system, stem cells from both cell lines established prostaspheres at a 0.1% efficiency through asymmetric self-renewal and rapid proliferation of daughter progenitor cells. Spheres derived from both cell lines contained CD117+ and CD133+ stem cell subpopulations and basal progenitor cell subpopulations (p63+ and CK5+) but were negative for luminal cell CK8 markers at day 7. While some NRP152 sphere cells were androgen receptor (AR) positive at this timepoint, NRP154 cells were AR- up to 30 days of 3D culture. The regenerative capacity of the stem/progenitor cells was demonstrated by in vivo tissue recombination with urogenital sinus mesenchyme (UGM) and renal grafting in nude mice. While stem/progenitor cells from NRP152 spheroids generated normal prostate structures, CSCs and progeny cells from NRP154 tumoroids generated tumor tissues that were characterized by immunohistochemistry. Atypical hyperplasia and prostatic intraepithelial neoplasia (PIN) lesions progressed to adenocarcinoma with kidney invasion over 4 months. This provides clear evidence that prostate CSCs can repopulate new tumor growth outside the prostate gland that rapidly progresses to poorly differentiated adenocarcinoma with invasive capabilities. The dual in vitro/in vivo CSC model system presented herein provides a novel platform for screening therapeutic agents that target prostate CSCs for effective combined treatment protocols for local and advanced disease stages.

Metformin inhibits gastric cancer cell proliferation by regulation of a novel Loc100506691-CHAC1 axis.

Long noncoding RNAs (lncRNAs) are a group of nonprotein coding transcripts that play a critical role in cancer progression. However, the role of lncRNA in metformin-induced inhibition of cell growth and its biological function in gastric cancer remain largely unknown. In this study, we identified an oncogenic lncRNA, Loc100506691, the expression of which was decreased in gastric cancer cells with metformin treatment. Moreover, Loc100506691 was significantly overexpressed in gastric cancer compared with adjacent normal tissues (p < 0.001), and high Loc100506691 expression was significantly correlated with poor survival of patients with gastric cancer. Additionally, Loc100506691 knockdown could significantly suppress gastric cancer cell growth in vitro, and ectopic Loc100506691 expression accelerated tumor growth in an in vivo mouse model. Analysis of the cell cycle revealed that Loc100506691 knockdown induced cell cycle arrest at the G2/M phase by impairing cell entry from the G2/M to G1 phase. Loc100506691 negatively regulated CHAC1 expression by modulating miR-26a-5p/miR-330-5p expression, and CHAC1 knockdown markedly attenuated Loc100506691 knockdown-induced gastric cancer cell growth and motility suppression. We concluded that anti-proliferative effects of metformin in gastric cancer may be partially caused by suppression of the Loc100506691-miR-26a-5p/miR-330-5p-CHAC1 axis.

Increased early activation of CD56dimCD16dim/- natural killer cells in immunological non-responders correlates with CD4+ T-cell recovery.

BACKGROUND: Natural killer (NK) cells play a critical role in suppressing human immunodeficiency virus-1 (HIV-1) infection, but knowledge on whether and how NK cells affect immune reconstitution in HIV-1-infected individuals who receive antiretroviral therapy (ART) is limited. METHODS: We performed a case-control study with 35 healthy individuals and 66 HIV-1-infected patients including 32 immunological non-responders (INRs) with poor CD4+ T-cell recovery (<500 cells/µL after 4 years of ART) and 34 immunological responders (IRs) with improved CD4+ T-cell recovery (>500 cells/µL after 4 years of ART). NK cell phenotype, receptor repertoire, and early activation in INRs and IRs were investigated by flow cytometry. RESULTS: A significantly higher proportion of CD56dimCD16dim/- NK cells was observed in INRs than IRs before ART and after 4 years of ART. The number of CD56dimCD16dim/- NK cells was inversely correlated with CD4+ T-cell counts in INRs before ART (r = -0.344, P = 0.050). The more CD69-expressing NK cells there were, the lower the CD4+ T-cell counts and ΔCD4, and these correlations were observed in INRs after ART (r = -0.416, P = 0.019; r = -0.509, P = 0.003, respectively). Additionally, CD69-expressing CD56dimCD16dim/- NK cells were more abundant in INRs than those in IRs (P  = 0.018) after ART, both of which had an inverse association trend towards significance with CD4+ T-cell counts. The expression of the activating receptors NKG2C, NKG2D, and NKp46 on CD56dimCD16dim/- NK cell subsets were higher in IRs than that in INRs after 4 years of ART (all P < 0.01). Strong inverse correlations were observed between CD69 expression and NKG2C, NKG2A-NKG2C+, NKG2D, and NKp46 expression on CD56dimCD16dim/- NK cells in INRs after ART (NKG2C: r = -0.491, P = 0.004; NKG2A-NKG2C+: r = -0.434, P = 0.013; NKG2D: r = -0.405, P = 0.021; NKp46: r = -0.457, P = 0.008, respectively). CONCLUSIONS: INRs had a larger number of CD56dimCD16dim/- NK cells characterized by higher activation levels than did IRs after ART. The increase in the CD56dimCD16dim/- NK cell subset may play an adverse role in immune reconstitution. Further functional studies of CD56dimCD16dim/- NK cells in INRs are urgently needed to inform targeted interventions to optimize immune recovery.

Hepatoma-derived growth factor participates in concanavalin A-induced hepatitis.

Hepatitis is an important health problem worldwide. Novel molecular targets are in demand for detection and management of hepatitis. Hepatoma-derived growth factor (HDGF) has been delineated to participate in hepatic fibrosis and liver carcinogenesis. However, the relationship between hepatitis and HDGF remains unclear. This study aimed to elucidate the role of HDGF during hepatitis using concanavalin A (ConA)-induced hepatitis model. In cultured hepatocytes, ConA treatment-elicited HDGF upregulation at transcriptional level and promoted HDGF secretion while reducing intracellular HDGF protein level and cellular viability. Similarly, mice receiving ConA administration exhibited reduced hepatic HDGF expression and elevated circulating HDGF level, which was positively correlated with serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. By using HDGF knockout (KO) mice, it was found the ConA-evoked cell death was prominently alleviated in KO compared with control. Besides, it was delineated HDGF ablation conferred protection by suppressing the ConA-induced neutrophils recruitment in livers. Above all, the ConA-mediated activation of tumor necrosis factor-α (TNF-α)/interleukin-1ß (IL-1ß)/interleukin-6 (IL-6)/cyclooxygenase-2 (COX-2) inflammatory signaling was significantly abrogated in KO mice. Treatment with recombinant HDGF (rHDGF) dose-dependently stimulated the expression of TNF-α/IL-1ß/IL-6/COX-2 in hepatocytes, further supporting the pro-inflammatory function of HDGF. Finally, application of HDGF antibody not only attenuated the ConA-mediated inflammatory cascade in hepatocytes, but also ameliorated the ConA-induced hepatic necrosis and AST elevation in mice. In summary, HDGF participates in ConA-induced hepatitis via neutrophils recruitment and may constitute a therapeutic target for acute hepatitis.

Impact of main vessel calcification on procedural and clinical outcomes of bifurcation lesion undergoing provisional single-stenting intervention: a multicenter, prospective, observational study.

BACKGROUND: Few data on the combined effects of bifurcation and calcification on coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI) are available. This study evaluated the impact of main vessel (MV) calcification on the procedural and long-term outcomes in patients with CAD who underwent provisional single stent PCI. METHODS: This is a multicenter, prospective, observational study. Patients with bifurcation lesions were enrolled at 10 PCI centers in China from January 2015 to December 2017. Intravascular ultrasound or optical coherence tomography was performed in all patients to evaluate the MV calcification. Patients were treated with provisional single stent strategy using drug eluting stents and followed-up at 1 month, 6 months and 12 months after discharge by telephone contact or outpatient visit. Repeated coronary imaging was performed within one year. We compared the procedural success rates in MV and in side branch (SB), and target lesion failure (TLF), defined as a composite of cardiac death, non-fatal myocardial infarction, definite or possible stent thrombosis and target lesion revascularization between patients with and without MV calcification. RESULTS: A total of 185 subjects were enrolled according to the inclusion and exclusion criteria of this study. MV calcification was detected in 119 (64.3%, calcification group) and not found in 66 (35.7%, non-calcification group) patients. The angiographic success rate of MV was 95.8% in the calcification group and 97.0% in the non-calcification group (P = 0.91); the angiographic success rate of SB was 32.8% in the calcification group and 53.0% in the non-calcification group (P < 0.05). During the one-year follow-up period, TLF occurred in 14 (11.8%) patients in the calcification group and in 13 (19.7%) in the non-calcification group (P = 0.31). Multivariate regression analysis showed the same result (HR = 1.23, 95% CI: 0.76-1.52, P = 0.47). Calcification on group had higher recurrent angina than non-calcification group (13.51% vs. 17.65%, P < 0.05). CONCLUSIONS: In patients with coronary bifurcation lesion treated with provisional one stent approach, calcification of MV is associated with lower SB procedural success rate, it could increase recurrence of angina; however, it was not associated with an increased risk of TLF.

Sex Differences Associated With Circulating PCSK9 in Patients Presenting With Acute Myocardial Infarction.

A limited number of studies have explored whether the role of circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) in the pathogenesis of acute myocardial infarction (AMI) is sex specific. The purpose of the present study was to examine sex differences in plasma PCSK9 in Chinese patients with AMI. In this study, a total of 281 records from patients presenting with AMI were analyzed.We compared hospital data and plasma PCSK9 levels by sex difference for inpatients presenting with AMI. After 1 year of follow-up, major adverse cardiac events(MACE) were recorded. A Cox proportional hazards model was used to calculate hazard ratios with 95% confidence intervals. We found that, compared with male groups, PCSK9 levels were higher in female patients not only for overall patients with AMI but also for patients with ST-elevation myocardial infarction (STEMI) (median: 273.6 [215.6-366.8] vs. 325.1 [247.5-445.3] ng/ml, P = 0.0136; 273.4 [215.6-369.7] vs. 317.1 [249.6-450.1], P = 0.0275, respectively). The cumulative incidence of cardiac death and 1-year MACE were significantly higher in the female group compared with male group (10% vs. 2.74%, P = 0.025; 15% vs. 4.11%, P = 0.0054, respectively). On multivariate Cox regression analysis, female sex, total triglyceride, glycosylated hemoglobin A, and homocysteic acid were independent risk factors of 1-year MACE. There was no significant correlation between PCSK9 and 1-year MACE in total AMI patients. In conclusion, PCSK9 levels and 1-year MACE were higher in women with AMI than in men with AMI, however, female sex but not PCSK9 were significant correlated with the 1-year MACE. The clinical implications of this finding are worthy of further investigations and must be confirmed in larger cohorts.

Kinome-Wide siRNA Screening Identifies Src-Enhanced Resistance of Chemotherapeutic Drugs in Triple-Negative Breast Cancer Cells.

Background: Chemotherapy is the main treatment for triple-negative breast cancer (TNBC), which lack molecular markers for diagnosis and therapy. Cancer cells activate chemoresistant pathways and lead to therapeutic failure for patients with TNBC. Several kinases have been identified as chemoresistant genes. However, the involvement of kinases in the chemoresistance in TNBC cells is not fully understood. Methods: We employed a kinome siRNA library to screen whether targeting any kinases could increase the chemosensitivity of TNBC cell lines. The effects of kinase on cell viability in various breast cancer cells were validated with ATP level and colony formation. Protein expression and phosphorylation were determined by immunoblotting. The Cancer Genome Atlas (TCGA) dataset was collected to analyze the correlation of Src expression with prognosis of TNBC patients. Results: Primary screening and validation for the initial hits showed that Src kinase was a potential doxorubicin-resistant kinase in the TNBC cell lines MDA-MB-231 and Hs578T. Both siRNA against Src and the Src inhibitor dasatinib enhanced the cytotoxic effects of doxorubicin in TNBC cells. Moreover, phosphorylation of AKT and signal transducer and activator of transcription 3 (STAT3), downstream effectors of Src, were accordingly decreased in Src-silenced or -inhibited TNBC cells. Additionally, TCGA data analysis indicated that Src expression levels in tumor tissues were higher than those in tumor-adjacent normal tissues in patients with TNBC. High co-expression level of Src and STAT3 was also significantly correlated with poor prognosis in patients. Conclusion: Our results showed that Src-STAT3 axis might be involved in chemoresistance of TNBC cells.

Comprehensive identification of microRNA arm selection preference in lung cancer: miR-324-5p and -3p serve oncogenic functions in lung cancer.

MicroRNA (miRNA/miR) dysfunction is a hallmark of lung cancer, and results in the dysregulation of tumor suppressors and oncogenes during lung cancer progression. Selection of the 5p and 3p arms of miRNA is a mechanism that improves the modulation of miRNA biological functions and complicates the regulatory network in human types of cancer. However, the involvement of arm selection preference of miRNA in lung cancer remains unclear. In the present study, changes in miRNA arm selection preference were comprehensively identified in lung cancer and corresponding adjacent normal tissues by analyzing The Cancer Genome Atlas. Arm selection was revealed to be consistent in the majority of miRNAs in lung cancer. Only a few miRNAs had significantly altered arm selection preference in lung cancer. Among these, the biological functions of the individual arms of miR-324 were investigated further. The data revealed that miR-324-5p and -3p were significantly overexpressed in lung cancer cells. Ectopic expression of miR-324-5p significantly promoted cell proliferation and invasion in lung cancer cells, while miR-324-3p overexpression significantly increased cell proliferation but did not alter the invasion of lung cancer cells. In conclusion, the arm selection preference of miRNA may be an additional mechanism through which biological functions are modulated. The results of the present study provide a novel insight into the underlying mechanisms of lung cancer and may direct research into future therapies.

Association of single nucleotide polymorphisms in CACNA 1A/CACNA 1C/CACNA 1H calcium channel genes with diabetic peripheral neuropathy in Chinese population.

The present study was conducted to explore the correlations between single nucleotide polymorphisms (SNPs) in the calcium channel CACNA 1A, CACNA 1C, and CACNA 1H genes and diabetic peripheral neuropathy (DPN) amongst the Chinese population. In total, 281 patients diagnosed with type 2 diabetes participated in the present study. These patients were divided into the case group, which was subdivided into the DPN (143 cases) and the non-DPN groups (138 cases). Subsequently, 180 healthy individuals that had undergone routine health examinations were also recruited and assigned to the control group. PCR-restriction fragment length polymorphism (PCR-RFLP) was used to detect the genotype and allele frequencies of CACNA 1A, CACNA 1C, and CACNA 1H genes; logistic regression analysis to investigate the association of gene polymorphisms with DNP. Gene-gene interactions were then detected by generalized multifactor dimensionality reduction (GMDR). The results revealed that CACNA 1A rs2248069 and rsl6030, CACNA 1C rs216008 and rs2239050, and CACNA 1H rs3794619, and rs7191246 SNPs were all associated with DPN, while rs2248069, rsl6030, rs2239050, and rs7191246 polymorphisms were attributed to the susceptibility to DPN. It was also observed that the optimal models were three-, four- and five-dimensional models with a prediction accuracy of 61.05% and the greatest consistency of cross-validation was 10/10. In summary, these findings demonstrated that the SNPs in the CACNA 1A, CACNA 1C, and CACNA 1H genes were involved in the pathophysiology of DPN. In addition, polymorphisms in the CACNA 1A, CACNA 1C, and CACNA 1H genes and their interactions also had effects on DPN.

Effect and Mechanism of EGFL7 Downregulation in Human Osteosarcoma Cells on the Biological Function of Co-cultured HUVEC.

BACKGROUND: Even though epidermal growth factor-like domain 7 is known to be overexpressed in osteosarcoma and is associated with poor clinical outcome, few reports are available regarding its mechanism. AIMS: The objective of this study was to explore the effect and mechanism of downregulating epidermal growth factor-like domain 7 expression in a human osteosarcoma cell line on the biological function of co-cultured human umbilical vein endothelial cells. STUDY DESIGN: Cell study. METHODS: In the present study, human osteosarcoma cell lines U2OS, Saos-2, HOS, and MG63, and normal human osteoblasts were cultured in Dulbecco's Modified Eagle Medium containing 10% fetal bovine serum and 1x antibiotics at 37 °C and 5% CO2 in an incubator. Of the four osteosarcoma cell lines, U2OS expresses the highest level of epidermal growth factor-like domain 7 mRNA as determined using quantitative reverse transcription polymerase chain reaction. With the knockdown of epidermal growth factor-like domain 7 in U2OS and human umbilical vein endothelial cells by lentivirus, the proliferation and apoptosis of U2OS and human umbilical vein endothelial cells were investigated using MTT and flow cytometry assays. After the co-culture of human umbilical vein endothelial cells and epidermal growth factor-like domain 7-knockdown U2OS, the in vitro effects on cell proliferation, apoptosis, adhesion, migration, and the angiogenic ability of human umbilical vein endothelial cells were detected using MTT, flow cytometry, Transwell, and tube formation assays, respectively. The expressions of phosphoinositide 3-kinase, phospho-Akt, total Akt, and vascular endothelial growth factor in human umbilical vein endothelial cells were detected using western blot assay. RESULTS: Lentivirus with epidermal growth factor-like domain 7 shRNA could not significantly affect the proliferation and apoptosis of both U2OS and human umbilical vein endothelial cells, whereas the knockdown of epidermal growth factor-like domain 7 in U2OS could significantly inhibit the migration, adhesion, and angiogenic ability of co-cultured human umbilical vein endothelial cells. In addition, the expressions of phosphoinositide 3-kinase, phospho-Akt, and vascular endothelial growth factor in human umbilical vein endothelial cells decreased after co-culturing with epidermal growth factor-like domain 7-knockdown U2OS. CONCLUSION: Epidermal growth factor-like domain 7-knockdown U2OS cells inhibit the migration, adhesion, and angiogenesis of co-cultured human umbilical vein endothelial cells by diminishing phosphoinositide 3-kinase, Akt signaling pathway activity and vascular endothelial growth factor expression.

Saikosaponin a Induces Apoptosis through Mitochondria-Dependent Pathway in Hepatic Stellate Cells.

Saikosaponin a (SSa) is one of the main active components of Bupleurum falcatum. It is commonly used to treat liver injury and fibrosis in traditional Chinese medicine. Our previous study showed that SSa induces apoptosis and inhibits the proliferation of rat hepatic stellate cell (HSC) line HSC-T6. The aim of the present study was to elucidate the mechanism of SSa-mediated apoptosis. Rat HSC cell line HSC-T6 and human HSC cell line LX-2 were used in this study. SSa triggered cell death mainly by apoptosis, as indicated by the typical morphological changes, sub-G1 phase of cell cycle increase, and activation of the caspase-9/caspase-3 cascade. In addition, SSa-induced apoptosis was partially inhibited by the caspase-3 inhibitor Z-DEVD-FMK, suggesting an involvement of caspase-3 dependent and independent pathways. Moreover, SSa upregulated pro-apoptotic proteins [BAK, Bcl-2-associated death promoter (BAD), and p53 upregulated modulator of apoptosis (PUMA)] and downregulated anti-apoptotic proteins (Bcl-2). In the mitochondria, SSa triggered the translocation of BAX and BAK from the cytosol to the outer membrane, resulting in a reduction of mitochondrial functions and membrane potential and subsequent release of apoptotic factors. Therefore, this study demonstrates that SSa induces apoptosis through the intrinsic mitochondrial-dependent pathway in HSCs.

Ginsenoside Rg1 protects against neurodegeneration by inducing neurite outgrowth in cultured hippocampal neurons.

Ginsenoside Rg1 (Rg1) has anti-aging and anti-neurodegenerative effects. However, the mechanisms underlying these actions remain unclear. The aim of the present study was to determine whether Rg1 affects hippocampal survival and neurite outgrowth in vitro after exposure to amyloid-beta peptide fragment 25-35 (Aß25-35), and to explore whether the extracellular signal-regulated kinase (ERK) and Akt signaling pathways are involved in these biological processes. We cultured hippocampal neurons from newborn rats for 24 hours, then added Rg1 to the medium for another 24 hours, with or without pharmacological inhibitors of the mitogen-activated protein kinase (MAPK) family or Akt signaling pathways for a further 24 hours. We then immunostained the neurons for growth associated protein-43, and measured neurite length. In a separate experiment, we exposed cultured hippocampal neurons to Aß25-35 for 30 minutes, before adding Rg1 for 48 hours, with or without Akt or MAPK inhibitors, and assessed neuronal survival using Hoechst 33258 staining, and phosphorylation of ERK1/2 and Akt by western blot analysis. Rg1 induced neurite outgrowth, and this effect was blocked by API-2 (Akt inhibitor) and PD98059 (MAPK/ERK kinase inhibitor), but not by SP600125 or SB203580 (inhibitors of c-Jun N-terminal kinase and p38 MAPK, respectively). Consistent with this effect, Rg1 upregulated the phosphorylation of Akt and ERK1/2; these effects were reversed by API-2 and PD98059, respectively. In addition, Rg1 significantly reversed Aß25-35-induced apoptosis; this effect was blocked by API-2 and PD98059, but not by SP600125 or SB203580. Finally, Rg1 significantly reversed the Aß25-35-induced decrease in Akt and ERK1/2 phosphorylation, but API-2 prevented this reversal. Our results indicate that Rg1 enhances neurite outgrowth and protects against Aß25-35-induced damage, and that its mechanism may involve the activation of Akt and ERK1/2 signaling.

Enhancement of sodium taurocholate to the absorption of cefquinome.

The objective of the research was to detect the enhancement effect of sodium taurocholate on the absorption of cefquinome both in Caco-2 cells and rats. The absorption efficiency of cefquinome was determined by high performance liquid chromatography and calculated with apparent permeability coefficients (Papp) after Caco-2 cell monolayers treated odium taurocholate(2 mmol/L) and cefquinome. The results showed that the absorption of cefquinome in Caco-2 cell monolayers was significantly increased with the sodium taurocholate (2mmol/L). Similar results were also detected in the rats orally administrated with 1 mL PBS of cefquinome (20mg/mL) containing different concentration of sodium taurocholate (5 mmol/L, 10mmol/L and 20mmol/L) respectively. Compared with control group, sodium taurocholate at 10 and 20 mmol/L increased the absorption of cefquinome in rats from 0.26±0.04µg/mL to 0.57±0.03µg/mL, 0.78 ±0.07µg/mL respectively. These results indicated that sodium taurocholate could increase the intestinal permeability in a concentration-dependent mode, which will be useful for clinical treatment.

[Ecological adaptability evaluation of peanut cultivars based on biomass and nutrient accumulation].

To identify the good peanut cultivars with the properties of high yield, high nutrient use efficiency and wide adaptability, 19 selected peanut cultivars were planted in the low champaign area and piedmont plain area of Hebei Province. By using principal component analysis, the adaptability of these 19 cultivars was evaluated for different ecological regions through comparing their 16 main traits including biomass and nutrient parameters. According to the critical value of principal component (>1.0), the 16 biomass and nutrient characteristics were integrated into 4 principal components which accounted for 85% of the original information. The results indicated that there were obvious differences in yield and nutrient use efficiency for the peanut cultivars in different ecological regions. The 19 peanut cultivars were classified into 2 groups according to their ecological adaptability, and the cultivars from the group with wide adaptability could further be divided into 3 categories according to their yield and nutrient use efficiency. Among these cultivars, Yuhua 9719, Jihua 0212-4, Weihua 10, Yuhua 15, Puhua 28 and Jihua 10 were selected as the better peanut cultivars with the properties of high yield, high nutrient use efficiency and wide adaptability.

Effect of Melatonin on the Extracellular-Regulated Kinase Signal Pathway Activation and Human Osteoblastic Cell Line hFOB 1.19 Proliferation.

It has been shown that melatonin may affect bone metabolism. However, it is controversial whether melatonin could promote osteoblast proliferation, and the precise molecular mechanism of melatonin on osteoblast proliferation is still obscure. In this study, the results of the CCK-8 assay showed that melatonin significantly promoted human osteoblastic cell line hFOB 1.19 cell proliferation at 1, 2.5, 5, 10, 25, 50 and 100 µM concentrations for 24 h, but there were no significant differences among the groups. Western blot demonstrated that 10 µM melatonin significantly promoted ERK1/2 phosphorylation. Furthermore, we also detected the phosphorylation of c-Raf, MEK1/2, p90RSK and MSK1, and all of them increased with 10 µM melatonin. U0126 (a selective inhibitor of MEK that disrupts downstream activation of ERK1/2) downregulated the phosphorylation of ERK1/2, p90RSK and MSK1. U0126 also attenuated the proliferation of osteoblasts stimulated by melatonin. In conclusion, this study for the first time indicates that melatonin (10 nM-100 µM) promotes the proliferation of a human osteoblastic cell line hFOB 1.19 through activation of c-Raf, MEK1/2, ERK1/2, p90RSK and MSK1.

Hepatoma-derived growth factor/nucleolin axis as a novel oncogenic pathway in liver carcinogenesis.

Hepatoma-derived growth factor (HDGF) overexpression is involved in liver fibrosis and carcinogenesis. However, the receptor(s) and signaling for HDGF remain unclear. By using affinity chromatography and proteomic techniques, nucleolin (NCL) was identified and validated as a HDGF-interacting membrane protein in hepatoma cells. Exogenous HDGF elicited the membrane NCL accumulation within 0.5 hour by protein stabilization and transcriptional NCL upregulation within 24 hours. Blockade of surface NCL by antibodies neutralization potently suppressed HDGF uptake and HDGF-stimulated phosphatidylinositol 3-kinase (PI3K)/Akt signaling in hepatoma cells. By using rescectd hepatocellular carcinoma (HCC) tissues, immunohistochemical analysis revealed NCL overexpression was correlated with tumour grades, vascular invasion, serum alpha-fetoprotein levels and the poor survival in HCC patients. Multivariate analysis showed NCL was an independent prognostic factor for survival outcome of HCC patients after surgery. To delineate the role of NCL in liver carcinogenesis, ectopic NCL overexpression promoted the oncogenic behaviours and induced PI3K/Akt activation in hepatoma cells. Conversely, NCL knockdown by RNA interference attenuated the oncogenic behaviours and PI3K/Akt signaling, which could be partially rescued by exogenous HDGF supply. In summary, this study provides the first evidence that surface NCL transmits the oncogenic signaling of HDGF and facilitates a novel diagnostic and therapeutic target for HCC.

Renal denervation suppresses atrial fibrillation in a model of renal impairment.

BACKGROUND: A close association exists between renal impairment (RI) and atrial fibrillation (AF) occurrence. Increased activity of the sympathetic nervous system (SNS) may contribute to the development of AF associated with RI. Renal denervation (RDN) decreases central sympathetic activity. OBJECTIVE: The main objective of the study was to explore the effects of RDN on AF occurrence and its possible mechanisms in beagles with RI. METHODS: Unilateral RI was induced in beagles by embolization of small branches of the renal artery in the right kidney using gelatin sponge granules in Model (n = 6) and RDN group (n = 6). The Sham group (n = 6) underwent the same procedure, except for embolization. Then animals in RDN group underwent radiofrequency ablation of the renal sympathetic nerve. Cardiac electrophysiological parameters, blood pressure, left ventricular end-diastolic pressure, and AF inducibility were investigated. The activity of the SNS, renin-angiotensin-aldosterone system (RAAS), inflammation and atrial interstitial fibrosis were measured. RESULTS: Embolization of small branches of the renal artery in the right kidney led to ischemic RI. Heart rate, P wave duration and BP were increased by RI, which were prevented or attenuated by RDN. Atrial effective refractory period was shortened and AF inducibility was increased by RI, which were prevented by RDN. Antegrade Wenckebach point was shortened, atrial and ventricular rates during AF were increased by RI, which were attenuated or prevented by RDN. Levels of norepinephrine, renin and aldosterone in plasma, norepinephrine, angiotensin II, aldosterone, interleukin-6 and high sensitivity C-reactive protein in atrial tissue were elevated, and atrial interstitial fibrosis was enhanced by RI, which were attenuated by RDN. CONCLUSIONS: RDN significantly reduced AF inducibility, prevented the atrial electrophysiological changes in a model of RI by combined reduction of sympathetic drive and RAAS activity, and inhibition of inflammation activity and fibrotic pathway in atrial tissue.