The interplay of oxidative stress and ARMS2-HTRA1 genetic risk in neovascular AMD.

Age-related macular degeneration (AMD) is the leading cause of vision loss in adults over 60 years old globally. There are two forms of advanced AMD: "dry" and "wet". Dry AMD is characterized by geographic atrophy of the retinal pigment epithelium and overlying photoreceptors in the macular region; whereas wet AMD is characterized by vascular penetrance from the choroid into the retina, known as choroidal neovascularization (CNV). Both phenotypes eventually lead to loss of central vision. The pathogenesis of AMD involves the interplay of genetic polymorphisms and environmental risk factors, many of which elevate retinal oxidative stress. Excess reactive oxygen species react with cellular macromolecules, forming oxidation-modified byproducts that elicit chronic inflammation and promote CNV. Additionally, genome-wide association studies have identified several genetic variants in the age-related maculopathy susceptibility 2/high-temperature requirement A serine peptidase 1 (ARMS2-HTRA1) locus associated with the progression of late-stage AMD, especially the wet subtype. In this review, we will focus on the interplay of oxidative stress and HTRA1 in drusen deposition, chronic inflammation, and chronic angiogenesis. We aim to present a multifactorial model of wet AMD progression, supporting HTRA1 as a novel therapeutic target upstream of vascular endothelial growth factor (VEGF), the conventional target in AMD therapeutics. By inhibiting HTRA1's proteolytic activity, we can reduce pro-angiogenic signaling and prevent proteolytic breakdown of the blood-retina barrier. The anti-HTRA1 approach offers a promising alternative treatment option to wet AMD, complementary to anti-VEGF therapy.

Probiotics protect against RSV infection by modulating the microbiota-alveolar-macrophage axis.

Respiratory syncytial virus (RSV) is leading cause of respiratory tract infections in early childhood. Gut microbiota is closely related with the pulmonary antiviral immunity. Recent evidence shows that gut dysbiosis is involved in the pathogenesis of RSV infection. Therefore; pharmacological and therapeutic strategies aiming to readjust the gut dysbiosis are increasingly important for the treatment of RSV infection. In this study, we evaluated the therapeutic effects of a probiotic mixture on RSV-infected mice. This probiotic mixture consisted of Lactobacillus rhamnosus GG, Escherichia coli Nissle 1917 and VSL#3 was orally administered to neonatal mice on a daily basis either for 1 week in advance or for 3 days starting from the day of RSV infection. We showed that administration of the probiotics protected against RSV-induced lung pathology by suppressing RSV infection and exerting an antiviral response via alveolar macrophage (AM)-derived IFN-ß. Furthermore, administration of the probiotics reversed gut dysbiosis and significantly increased the abundance of short-chain fatty acid (SCFA)-producing bacteria in RSV-infected mice, which consequently led to elevated serum SCFA levels. Moreover, administration of the probiotics restored lung microbiota in RSV-infected mice. We demonstrated that the increased production of IFN-ß in AMs was attributed to the increased acetate in circulation and the levels of Corynebacterium and Lactobacillus in lungs. In conclusion, we reveal that probiotics protect against RSV infection in neonatal mice through a microbiota-AM axis, suggesting that the probiotics may be a promising candidate to prevent and treat RSV infection, and deserve more research and development in future.

Acupuncture for Cancer-Induced Bone Pain in Animal Models: A Systemic Review and Meta-Analysis.

BACKGROUND: Cancer-induced bone pain (CIBP) is a highly prevalent symptom, which afflicts vast majority of patients who suffer from cancer. The current treatment options failed to achieve satisfactory effect and the side effects were prominent. Recent randomized controlled trials (RCTs) of animal demonstrate the benefit of acupuncture for CIBP. We sought to determine if the pooled data from available RCTs supports the use of acupuncture for CIBP. METHODS: A literature search for randomized controlled trials was conducted in six electronic databases from inception to May 31, 2019. Meta-analysis was performed with Review Manager 5.3 software; the publication bias was assessed by Stata 12.0 software. We used random effects model for pooling data because heterogeneity is absolute among studies to some extent. RESULTS: Twenty-four trials were included in the review, of which 12 trials provided detailed data for meta-analyses. Preliminary evidence indicates that compared to wait list/sham group, acupuncture was effective on increasing paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). Compared to medicine, acupuncture was less effective on PWT, but as effective as medicine on PWL. Acupuncture can reinforce medicine's effect on PWT and PWL. Compared to the control group, acupuncture was superior to increase body weight (BW), decrease spinal cord glial fibrillary acidic protein (GFAP), and interleukin-1ß (IL-1ß). Furthermore, some studies showed acupuncture delay or partially reverse morphine tolerance. Three studies found acupuncture has no effect on PWT, but 2 of them found acupuncture could enhance small dose of Celebrex's effect on CIBP. CONCLUSIONS: Acupuncture was superior to wait list/sham acupuncture on increasing PWT and has no less effect on increasing PWL compared to medicine; acupuncture improved the efficacy of drugs, increased the CIBP animals' body weight, and decreased their spinal cord GFAP and IL-1ß. High-quality studies are necessary to confirm the results.

Electroacupuncture Relieves Pain and Attenuates Inflammation Progression Through Inducing IL-10 Production in CFA-Induced Mice.

The therapeutic effect of electroacupuncture (EA) on inflammatory pain has been well recognized clinically, but the mechanism is unclear. Interleukin-10 (IL-10), which is produced by regulatory T (Treg) cell, is a key anti-inflammatory cytokine for relieving inflammatory pain. Therefore, the aim of this study is to investigate whether EA could inhibit CFA-induced pain and attenuate inflammation progression by regulating the activation of immunocyte and inducing the expression of IL-10. In this study, mice were treated with EA (2/100 Hz, 2 mA) for five consecutive days after 1 day of CFA injection. The behavioral tests were measured and analyzed after the daily EA treatment; then, hind paw, spinal cord, and spleen tissues were prepared for assessment. The results showed that EA treatment significantly increased the mechanical threshold and thermal latency after CFA injection and boosted the expression of IL-10 in paw and spinal cord tissues. EA treatment promoted Treg cells; suppressed macrophage and neutrophils cells; reduced the expression of IL-1ß, NLRP3, and TNF-α; and ultimately relieved inflammatory pain. The findings suggested that the analgesic and anti-inflammatory effect of EA treatment could be partially associated with suppression of pro-inflammatory cytokines mediated by induction of IL-10.

[Clinical Analysis of Efficacy and Prognosis in 300 Cases of Hematological Malignancies Receiving Allogeneic Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To investigate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of malignant hematopathy and its influencing factors. METHODS: The clinical data of 300 cases received hematopoietic stem cell transplantation due to malignant hematological diseases in Zhu Jiang Hospital of Southern Medical University from January 2010 to June 2018 were analyzed retrospectively, and the factors affecting hematopoietic reconstruction, disease-free survival (DFS) and overall survival (OS) were compared between haploidentical HSCT and HLA matched HSCT. RESULTS: The hematopoietic reconstitution rate, incidence of GVHD, posttransplant recurrence rate and disease-free survival (DFS) were not statistically different between HLA-metched and haploidentical colorts. However, compared with HLA-matched HSCT group the time of platelet implantation was prolonged, the recurrence-related mortality was higher, and the overall survival (OS) rate was lower in the haploidentical HSCT group. Univariate analyses showed that non-remission before transplantation, and grade Ⅲ, Ⅳ aGVHD were the risk factors for OS in both groups (P＜0.05). The age than 40 years old at the time of transplantation and unrelated donors were risk factors for OS in haploidentical HSCT group (P＜0.05). Multivariate analysis showed that non-remission before transplantation and grade Ⅲ, Ⅳ aGVHD were independent prognostic indictor for OS with relative risk (RR) of 4.4 (95% CI,1.5-13.4), 9.3 (95% CI,2.3-37.0), 11.0 (95% CI,3.2-37.3) (P＜0.05) in HLA-matched HSCT group. Unrelated donor, high-risk group, and gradeⅣaGVHD were independent prognostic indictors for OS with relative risk (RR) of 7.4 (95% CI,2.3-23.1), 2.4 (95% CI,1.3-4.5), 4.1(95% CI,1.6-10.5) (P＜0.05) in haploidentical HSCT group. CONCLUSION: The comprehensive curative effect of HLA-matched HSCT is better than the haploidentical HSCT in hematological malignancies. In haploidentical HSCT the selecting related donor is better than unrelated donors, which required more platelet transfusion support.

The combination of nonthyroidal illness syndrome and renal dysfunction further increases mortality risk in patients with acute myocardial infarction: a prospective cohort study.

BACKGROUND: Both nonthyroidal illness syndrome and renal dysfunction are associated with increased mortality risk in acute myocardial infarction (AMI). However, it is unclear whether combined NTIS and renal dysfunction further increase mortality risk. Therefore, our aim is to investigate whether combined NTIS and renal dysfunction further increases mortality risk in patients with acute myocardial infarction (AMI). METHODS: A total of 1295 inpatients with AMI were divided into normal group (n = 692), NTIS group (n = 139), renal dysfunction group (n = 304), and combined NTIS and renal dysfunction group (n = 160). Heart function, in-hospital, all-cause and cardiovascular mortality were compared among the four groups. RESULTS: After adjustment for age and sex, left ventricular ejection fraction was significantly lower in the combined group (48 ± 11%) than in the NTIS group (52 ± 10%, P = 0.017), the renal dysfunction group (52 ± 10%, P = 0.001) and the normal group (56 ± 8%, P < 0.001). After controlling for confounding factors, compared with the normal group, the NTIS and the renal dysfunction group represented higher risks of in-hospital mortality (OR: 3.643, P = 0.028; OR:3.135, P = 0.042, respectively), all-cause mortality (HR: 2.138, P = 0.007; HR: 2.050, P = 0.003, respectively), and cardiovascular mortality (HR:2.134, P = 0.042; HR:2.237, P = 0.010, respectively). Compared to those in the NTIS and the renal dysfunction group, the patients in the combined group showed a further increased risk for in-hospital mortality (OR:2.916, P = 0.039; OR:2.487, P = 0.036, respectively), all-cause mortality (HR: 1.939, P = 0.015; HR: 2.020, P = 0.002, respectively) and cardiovascular mortality (HR:2.420, P = 0.010; HR:2.303, P = 0.002, respectively). CONCLUSIONS: Both NTIS and renal dysfunction increase short-term in-hospital mortality, and long-term all-cause and cardiovascular mortality risk in patients with AMI. Furthermore, the coexistence of NTIS and renal dysfunction presents further increased mortality risk in AMI patients.

Low serum osteocalcin levels are correlated with left ventricular systolic dysfunction and cardiac death in Chinese men.

Osteocalcin is a newly identified type of cytokine secreted by osteoblasts, which has an endocrine function, mediates energy and glycol-lipid metabolism, and is closely related to cardiovascular diseases. In this study, we investigated the value of serum osteocalcin levels in predicting left ventricular systolic dysfunction and cardiac death. A total of 258 patients in the Department of Cardiology were included. Two-dimensional echocardiography was performed in all the subjects. The cardiac death of subjects occurring with a median follow-up of 4.6 years was informed via phone calls or the electronic medical records. The serum osteocalcin levels were measured using electrochemiluminescent immunoassay. We found that the median left ventricular ejection fractions (LVEFs) were 62% in men and 63% in women. In the men with a LVEF > 62%, the serum osteocalcin levels were significantly higher than in those with LVEF ≤ 62% (P = 0.042), whereas this difference was absent in the women. Both the serum osteocalcin (ß = 0.095, P = 0.028) and serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP; ß = -0.003, P < 0.01) levels remained independently significantly correlated with LVEF in the men but not in the women. Receiver operating characteristic (ROC) analyses of the men revealed that the serum osteocalcin (P = 0.007), serum NT-pro-BNP (P = 0.018) and serum osteocalcin + NT-pro-BNP (P < 0.01) levels were all significant in identifying left ventricular systolic dysfunction at baseline, but the pairwise comparisons of the three areas under the curves (AUCs) were all non-significant. The men in the lower osteocalcin level group at baseline suffered a greater risk of future cardiac death than those in the higher osteocalcin level group, whereas the result for NT-pro-BNP exhibited the opposite pattern. In conclusion, lower serum osteocalcin levels in the men could identify left ventricular systolic dysfunction and cardiac death in a manner that was not inferior to high serum NT-pro-BNP levels.

Roles of ST2, IL-33 and BNP in predicting major adverse cardiovascular events in acute myocardial infarction after percutaneous coronary intervention.

This study investigated roles of serum ST2, IL-33 and BNP in predicting major adverse cardiovascular events (MACEs) in acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). Blood samples were collected from the included AMI patients (n = 180) who underwent PCI. All patients were divided into the MACEs and MACEs-free groups. Enzyme-linked immunosorbent assay was performed to measure serum levels of ST2, IL-33 and BNP. Severity of coronary artery lesion was evaluated by Gensini score. Pearson correlation analysis was used. A receiver operating characteristics curve was drawn to evaluate the potential roles of ST2, IL-33 and BNP in predicting MACEs, and Kaplan-Meier curve to analyse the 1-year overall survival rate. Logistic regression analysis was conducted to analyse the independent risk factors for MACEs. Compared with the MACEs-free group, the serum levels of ST2, IL-33 and BNP were significantly higher in the MACEs group. Serum levels of ST2, IL-33 and BNP were positively correlated with each other and positively correlated with Gensini score. The area under curves of ST2, IL-33 and BNP, respectively, were 0.872, 0.675 and 0.902. The relative sensitivity and specificity were, respectively, 76.27% and 85.92%, 69.49% and 58.68%, as well as, 96.61% and 77.69%. Serum levels of ST2, IL-33 and BNP were independent risk factors for MACEs. The 1-year overall survival rate was higher in AMI patients with lower serum levels of ST2, IL-33 and BNP. In conclusion, serum levels of ST2, IL-33 and BNP have potential value in predicting MACEs in AMI patients undergoing PCI.

The PI3K/mTOR dual inhibitor BEZ235 suppresses proliferation and migration and reverses multidrug resistance in acute myeloid leukemia.

Aberrant activation of the PI3K/Akt/mTOR pathway contributes to the proliferation of malignant cells, and may confer resistance to chemotherapy in various malignancies, including acute myeloid leukemia (AML). Chemoresistance is the major reason for relapse in AML. RAD001 (everolimus) has been used at d1 and d7 of an induction chemotherapy regimen for AML, which has acceptable toxicity and may improve conventional chemotherapeutic treatment. Dual inhibitors of PI3K and mTOR overcome some of the intrinsic disadvantages of rapamycin and its derivatives. In this study, we evaluated the effects of BEZ235, a PI3K/mTOR dual inhibitor, on the multidrug-resistant AML cell lines HL-60/VCR and K562/ADR in vitro. BEZ235 dose-dependently inhibited the viability of HL-60/VCR and K562/ADR cells with the IC50 values of 66.69 and 71.44 nmol/L, respectively. BEZ235 (25-100 nmol/L) dose-dependently inhibited the migration of the two AML cell lines, and it also significantly sensitized the two AML cell lines to VCR and ADR. After treatment with BEZ235, the miR-1-3p levels were markedly increased in HL-60/VCR cells. Using TargetScan analysis and luciferase assays, we showed that miR-1-3p targeted BAG4, EDN1 and ABCB1, the key regulators of cell apoptosis, migration and multidrug resistance, and significantly decreased their levels in the two AML cell lines. Transfection of HL-60/VCR and K562/ADR cells with miR-1-3p-AMO to inhibit miR-1-3p could reverse the anti-proliferation effects of BEZ235. In conclusion, the PI3K/mTOR dual inhibitor BEZ235 effectively chemosensitizes AML cells via increasing miR-1-3p and subsequently down-regulating BAG4, EDN1 and ABCB1.

Sirolimus induces apoptosis and reverses multidrug resistance in human osteosarcoma cells in vitro via increasing microRNA-34b expression.

AIM: Multi-drug resistance poses a critical bottleneck in chemotherapy. Given the up-regulation of mTOR pathway in many chemoresistant cancers, we examined whether sirolimus (rapamycin), a first generation mTOR inhibitor, might induce human osteosarcoma (OS) cell apoptosis and increase the sensitivity of OS cells to anticancer drugs in vitro. METHODS: Human OS cell line MG63/ADM was treated with sirolimus alone or in combination with doxorubicin (ADM), gemcitabine (GEM) or methotrexate (MTX). Cell proliferation and apoptosis were detected using CCK-8 assay and flow cytometry, respectively. MiRNAs in the cells were analyzed with miRNA microarray. The targets of miR-34b were determined based on TargetScan analysis and luciferase reporter assays. The expression of relevant mRNA and proteins was measured using qRT-PCR and Western blotting. MiR-34, PAK1 and ABCB1 levels in 40 tissue samples of OS patients were analyzed using qRT-PCR and in situ hybridization assays. RESULTS: Sirolimus (1-100 nmol/L) dose-dependently suppressed the cell proliferation (IC50=23.97 nmol/L) and induced apoptosis. Sirolimus (10 nmol/L) significantly sensitized the cells to anticancer drugs, leading to decreased IC50 values of ADM, GEM and MTX (from 25.48, 621.41 and 21.72 µmol/L to 4.93, 73.92 and 6.77 µmol/L, respectively). Treatment of with sirolimus increased miR-34b levels by a factor of 7.5 in the cells. Upregulation of miR-34b also induced apoptosis and increased the sensitivity of the cells to the anticancer drugs, whereas transfection with miR-34b-AMO, an inhibitor of miR-34b, reversed the anti-proliferation effect of sirolimus. Two key regulators of cell cycle, apoptosis and multiple drug resistance, PAK1 and ABCB1, were demonstrated to be the direct targets of miR-34b. In 40 tissue samples of OS patients, significantly higher miR-34 ISH score and lower PAK5 and ABCB1 scores were detected in the chemo-sensitive group. CONCLUSION: Sirolimus increases the sensitivity of human OS cells to anticancer drugs in vitro by up-regulating miR-34b interacting with PAK1 and ABCB1. A low miR-34 level is an indicator of poor prognosis in OS patients.

A pilot study of prognostic value of non-invasive cardiac parameters for major adverse cardiac events in patients with acute coronary syndrome treated with percutaneous coronary intervention.

The objective of this study was to determine the combination of left ventricular ejection fraction (LVEF) and individual electrocardiographic parameters related to abnormal depolarization/repolarization or baroreceptor sensitivity that had the best predictive value for major adverse cardiac events (MACE) in patients with acute coronary syndrome (ACS). Patients with ACS who underwent coronary angiography and percutaneous coronary intervention (PCI) were included in this prospective study. Ventricular late potential (VLP), heart rate turbulence (HRT), heart rate variability (HRV), and T wave alternans (TWA) parameters were measured using 24 h Holter monitoring 2-4 weeks after onset of ACS. Initial and follow-up LVEF was measured by ultrasound. Patients were followed for at least 6 months to record the occurrence of MACE. Models using combinations of the individual independent prognostic factors found by multivariate analysis were then constructed to use for estimation of risk of MACE. In multivariate analysis, VLP measured as QRS duration, HRV measured as standard deviation of normal RR intervals, and followup LVEF, but none of the other parameters studied, were independent risk factors for MACE. Areas under ROC curve (AUCs) for combinations of 2 or all 3 factors ranged from 0.73 to 0.76. Combinations of any of the three independent risk factors for MACE in ACS patients with PCI improved prediction and, because these risk factors were obtained non-invasively, may have future clinical usefulness.

Neuroprotective effects of bis(7)-tacrine in a rat model of pressure-induced retinal ischemia.

The retinal ischemia-reperfusion model has been studied extensively and is an ideal animal model for studying clinical situations such as acute glaucoma and optic neuropathy. Our previous reports showed that bis(7)-tacrine had neuroprotective effects against glutamate-induced retinal ganglion cells damage through the drug's anti-NMDA receptor effects. Here, we investigated whether bis(7)-tacrine protects the retina from ischemic injury in a rat model. Retinal ischemia was induced by raising the intraocular pressure to 120 mmHg for 90 min. Rats received intraperitoneal injections of 0.2 mg/kg bis(7)-tacrine or saline at 30 min before ischemia, and then twice a day after retinal ischemia. Morphometric evaluation showed that bis(7)-tacrine dramatically reduced the retinal damage compared with the control group. Moreover, bis(7)-tacrine suppressed ischemia-induced reductions in a- and b-wave amplitudes of electroretinography. Protein levels of p53, the tumor suppressor gene known to induce apoptosis, were increased after ischemic injury, and treatment with bis(7)-tacrine reduced the expression of the protein. Our results suggest that bis(7)-tacrine has a neuroprotective effect against ischemic injury in the rat retina, possibly through the drug's anti-apoptotic effects. Bis(7)-tacrine may potentially be useful as a therapeutic drug in the management of ischemic retinal diseases.

[Effects of different lyophilizing protectants on lyophilized trehalose-loading red blood cells].

This study was purposed to evaluate the effect of different lyophilizing protectants including human albumin, glucan, polyvinyl pyrrolidone and glycerine on lyophilized trehalose-loading red blood cells (RBC), then to screen the optimal lyophilizing protectant. The RBC were incubated in 800 mmol/L concentration of trehalose solution at 37°C for 7 hours, and washed 3 times with PBS solution to obtain the trehalose-loading RBC. The trehalose-loading RBC in control group were directly lyophilized without lyophilizing protectants, the trehalose-loading RBC in the experimental group were mixed with Lyophilizing protectants. The samples of 2 groups were kept at room temperature for 30 minutes, pre-frozen at -80°C for 24 hours, then lyophilized in freeze-dryer for 24 hours. Finally the samples were quickly rehydrated by 6% HES at 37°C. The recovery rate and hemolysis rate of hemoglobin were detected by using cyanohemoglobin detection kit. The water content of unhydrated samples were detected at the same time. The results showed that when the moisture content of sample was 3% - 5%, the recovery rate of hemoglobin in control group was 33.57 ± 2.89%, and that in experimental group was 51.15 ± 1.98%, there was statistically significant difference between the control and experimental group (P < 0.05). When the different concentration of dextran solution was chosen as protectants, the recovery rate of hemoglobin of lyophilized RBC was obviously lower. The higher concentration of dextran, the better the recovery rate. The recovery rate of hemoglobin was 22.15 ± 4.12% when the concentration of dextran was 36%, there were statistically significant difference between the two groups (P < 0.05). When the different concentration of polyvinyl pyrrolidone (PVP) solutions was chosen as protectants, especially the concentration below 40%, the recovery rate of hemoglobin of lyophilized RBC was significantly belower than the control group, there was statistically significant difference between the two groups (P < 0.05). When 10% glycerol was used as protectants, the recovery rate of hemoglobin was 3.93 ± 1.80%. There was also statistically significant difference between the two groups (P < 0.05). It is concluded that human serum albumin shows an important protective effect on the lyophilization of the trehalose-loading red blood cells. The dextran and PVP at the concentration lower than 40% can decrease the protective effect of trehalose in cells. Glycerol can not be chosen as protectant for lyophilized trehalose-loading red blood cells.

Set9, NF-κB, and microRNA-21 mediate berberine-induced apoptosis of human multiple myeloma cells.

AIM: To investigate the mechanisms by which berberine suppressed the proliferation of human multiple myeloma cells. METHODS: Human U266 multiple myeloma cell line was tested. Cell proliferation, apoptosis, ultramicrostructure and secretion function were examined using Cell Counting Kit-8 (CCK8), flow cytometry (FCM), electron and fluorescence microscopy, as well as ELISA assay. The microRNAs (miRs) and transcription factors in U266 cells were detected using arrays and verified by qRT-PCR. EMSA and luciferase assays were used to verify the p65-dependent transactivation of miR-21 gene. RESULTS: Treatment of U266 cells with berberine (40-160 µmol/L) suppressed cell proliferation and IL-6 secretion in dose- and time-dependent manners. Meanwhile, berberine dose-dependently induced ROS generation, G(2)/M phase arrest and apoptosis in U266 cells, and decreased the levels of miR-21 and Bcl-2. Overexpression of miR-21 counteracted berberine-induced suppression of cell proliferation and IL-6 secretion. In U266 cells treated with berberine (80 µmol/L), the activity of NF-κB was decreased by approximately 50%, followed by significant reduction of miR-21 level. berberine (80-160 µmol/L) increased the level of Set9 (lysine methyltransferase) by more than 2-fold, caused methylation of the RelA subunit, which inhibited NF-κB nuclear translocation and miR-21 transcription. In U266 cells treated with berberine (80 µmol/L), knockdown of Set9 with siRNAs significantly increased NF-κB protein level accompanying with a partial recovery of proliferation. CONCLUSION: In U266 cells, berberine suppresses NF-κB nuclear translocation via Set9-mediated lysine methylation, leads to decrease in the levels miR21 and Bcl-2, which induces ROS generation and apoptosis.

[Determination of Pb, Cd and Cr in surface decorating materials of wood-based panels by microwave digestion-AAS].

With microwave-digestion as a sample decomposition technique and HNO3 and H2O2 as digestion reagent, the contents of Pb, Cd and Cr in surface decorating materials of wood-based panels were determined by atomic absorption spectrometry. The detection limit of Pb, Cd and Cr of FAAS is 0.12 microg x mL(-1), 0.029 microg x L(-1) and 0.146 microg x L(-1); respectively, the cadmium detection limit of GFAAS is 0.157 microg x L(-1). The precision of lead was between 0.8% and 3.0% and the recoveries ranged from 94% to 109.2%. The precision of cadmium was between 0.8% and 2.1%, and the recoveries ranged from 94.6% to 106.4%. The precision of chromium was between 1.8% and 4.9%, and the recoveries ranged from 98.8% to 107.7%. The method is accurate and reliable, and suitable and applicable to determining heavy metal of surface decorating materials of wood-based panels. The result is expected to provide scientific basis for establishing a corresponding Chinese national standard.

[Associations of glycated albumin level with coronary artery disease].

OBJECTIVE: To explore the associations of the level of glycated albumin (GA) with coronary artery disease (CAD). METHODS: A total of 306 patients undergoing coronary angiography (CA) were collected. There were 201 males and 105 females with an age range of 38-86 years. CA was the major diagnostic criteria of CAD. Metabolic syndrome was diagnosed according to the Guideline on Prevention & Treatment of Blood Lipid Abnormality in Chinese Adults. RESULTS: (1) CAD was found in 227 patients (74.2%). The levels of 2 h postprandial glucose, GA and hemoglobin A1c in the CAD patients were higher than those in the non-CAD counterparts (all P < 0.05). (2) In the subgroup of normal glucose tolerance (NGR), the CAD patients had a higher level of GA than the non-CAD patients ((15.0 ± 2.1)% vs (13.3 ± 1.7)%, P < 0.01). And the level of GA was higher in the patients with 1-vessel ((14.8 ± 2.1)% vs (13.3 ± 1.7)%, P < 0.05) and multi-vessel lesions ((15.1 ± 2.1)% vs (13.3 ± 1.7)%, P < 0.05) than that in the non-CAD counterparts (all P < 0.05). Similar results were obtained in the hyperglycemia subgroup. (3) Logistic regression demonstrated that the level of GA was independently correlated with CAD after adjusting other traditional factors among all subjects, NGR and hyperglycemia subgroup. CONCLUSIONS: The serum level of GA becomes significantly elevated the CAD patients. And it is an independent risk factor of CAD in both hyperglycemic and NGR patients.

[An efficient high-throughput screening assay against nuclear transport].

Nuclear transport, an essential cellular process of eukaryotic cells, plays critical roles in differentiation , development, as well as viral disease and oncogenesis, making the small molecules that target this process very intriguing not only in fundamental research but also in disease treatment. However, only one compound, Leptomycin B, is commercially available to inhibit nuclear transport. Therefore, it will be a great advantage to establish an assay that targets the whole nuclear transport pathway for screening and obtaining small molecule that regulates nuclear transport. In this study, we established an efficient nuclear transport assay based on the reconstitution of GFP by NZGFP and CZGFP. We constructed NZGFP-NES and CZGFP-NLS, making them locate in cytoplasm and nucleus separately. Their distribution will be changed when nuclear transport is interfered, resulting in co-localization of NZGFP-NES and CZGFP-NLS and subsequent reconstitution of fluorescent GFP. The inhibiting effect of Leptomycin B on nuclear transport can be sensitively detected by NZGFP-NES/CZGFP-NLS report system, providing an efficient assay for high-throughput screening of small molecule against nuclear transport.

[Salvianolic acid B inhibits ERK signal transduction pathway activated by transforming growth factor-ß1 in rat hepatic stellate cells].

OBJECTIVE: To investigate the effects of salvianolic acid B (SA-B) on extracellular signal-regulated kinase (ERK) signal transduction pathway activated by transforming growth factor-ß1 (TGF-ß1) in rat hepatic stellate cells (HSCs). METHODS: HSCs were isolated from male Sprague-Dawley rats by in situ perfusion and Nycodenz density-gradient centrifugation method. TGF-ß1 and SA-B were directly added to the serum-free medium of HSCs. Total and phosphorylated ERK, MEK, Raf and α-smooth muscle actin (α-SMA) and type I collagen were assayed by Western blotting. RESULTS: Phosphorylation of MEK in HSCs with or without TGF-ß1 was inhibited by SA-B; however, phosphorylation of Raf in HSCs with or without TGF-ß1 was not inhibited by SA-B. Expression of α-SMA in HSCs with TGF-ß1 was inhibited by SA-B. Combination of SA-B and the inhibitors of ERK (PD98059) can effectively inhibit the expression of α-SMA. SA-B also inhibited synthesization of type I collagen in HSCs with or without TGF-ß1. CONCLUSION: The action point of SA-B inhibiting ERK signaling induced by TGF-ß1 in HSCs is the inhibition of the phosphorylation of MEK. SA-B reduces the increase of expression of α-SMA and protein synthesization of type I collagen induced by TGF-ß1 by means of inhibiting ERK signaling in activated HSCs of rats.