Oxidative stress and antioxidant defense in detoxification systems of snake venom-induced toxicity

Snakebites remain a major life-threatening event worldwide. It is still difficult to make a positive identification of snake species by clinicians in both Western medicine and Chinese medicine. The main reason for this is a shortage of diagnostic biomarkers and lack of knowledge about pathways of venom-induced toxicity. In traditional Chinese medicine, snakebites are considered to be treated with wind, fire, and wind-fire toxin, but additional studies are required. Methods: Cases of snakebite seen at the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine were grouped as follows: fire toxin - including four cases of bites by Agkistrodon acutus and three bites by Trimeresurus stejnegeri - and wind-fire toxin - four cases of bites by vipers and three bites by cobras. Serum protein quantification was performed using LC-MS/MS. Differential abundance proteins (DAPs) were identified from comparison of snakebites of each snake species and healthy controls. The protein interaction network was constructed using STITCH database. Results: Principal component analysis and hierarchical clustering of 474 unique proteins exhibited protein expression profiles of wind-fire toxins that are distinct from that of fire toxins. Ninety-three DAPs were identified in each snakebite subgroup as compared with healthy control, of which 38 proteins were found to have significantly different expression levels and 55 proteins displayed no expression in one subgroup, by subgroup comparison. GO analysis revealed that the DAPs participated in bicarbonate/oxygen transport and hydrogen peroxide catabolic process, and affected carbon-oxygen lyase activity and heme binding. Thirty DAPs directly or indirectly acted on hydrogen peroxide in the interaction network of proteins and drug compounds. The network was clustered into four groups: lipid metabolism and transport; IGF-mediated growth; oxygen transport; and innate immunity. Conclusions: Our results show that the pathways of snake venom-induced toxicity may form a protein network of antioxidant defense by regulating oxidative stress through interaction with hydrogen peroxide.(AU)

Effects of XPO1 Inhibitor KPT-8602 on Proliferation and Apoptosis in U937 cells / 中山大学学报(医学科学版)

@#【Objective】To explore the effects and the possible mechanism of KPT- 8602，a novel selective inhibitor of nuclear export protein （XPO1），on proliferation，cell cycle and apoptosis in human histiocytic lymphoma cell line U937 cells.【Methods】U937 cells were treated with different concentrations of KPT- 8602. Cell viability was assessed by CCK-8 assay. The cell cycle distribution and the apoptosis rate were analyzed by flow cytometry. The proteins expression of XPO1，p-AKT，AKT，Cleaved Caspase-3，p21 were determined by Western blot. Fluorescence microscope was used in observing the intracellular location of XPO1. 【Results】 KPT- 8602 inhibited the growth of U937 cells in a dose- dependent（P<0.001）and time- dependent manner（P<0.001），but normal PBMC were unaffected. 48 h after treatment with KPT-8602，a higher proportion of cells in G1 phase was observed（P<0.001）and the apoptosis rate increased（P=0.016）with drug concentration in U937 cells. XPO1 protein expression of U937 cells was significantly higher than normal PBMC（P=0.003）. 48 h after treatment with KPT- 8602，the protein expression of XPO1 decreased（P=0.011），p-AKT decreased（P=0.011），and Cleaved Caspase- 3 increased（P=0.009）. In addition，the protein expression of p21，the cargo protein of XPO1，increased in both the nuclei and the cytoplasm（P<0.05）after treatment with KPT- 8602. XPO1 decreased in both the nuclei and the cytoplasm under the fluorescence microscope after treatment with KPT- 8602.【Conclusion】KPT- 8602 can inhibit the proliferation of U937 cells，block the cell cycle at G1 phase，and induce cell apoptosis，which may partially be attributed to the down-regulation of XPO1 and inhibition of PI3K/AKT signaling.

Influencing factorsof aortic pulse wave velocity in hypertensive patients / 心血管康复医学杂志

Objective : To analyze influencing factors of aortic pulse wave velocity (APWV) in patients with essential hypertension (EH).Methods : The 336 EH patients from our hospital were divided into elevated APWV group (n＝281) and normal APWV group (n＝55)- Clinical data were compared between two groups ,and multi-factor Logis-tic regression was used to analyze influencing factors of APWV in EH patients .Results : Compared with normal AP-WV group ,there were significant rise in age [ (56-71 ± 11-45) years vs-(62-98 ± 12-36) years] ,percentages of di-abetes mellitus (5-45% vs- 19-22%) ,obesity (18-18% vs- 23-84%) ,smoking (16-36% vs- 30-60%) , EH stage 3 (12-73% vs- 32-03%) ,body mass index [BMI , (22-53 ± 2-07) kg／m2 vs-(23-28 ± 2-04) kg／m2 ] ,systolic blood pressure SBP [ (139-64 ± 12-85) mmHg vs.(147-39 ± 13-30 ) mmHg] ,diastolic blood pressure DBP [ (93-18 ± 8-73) mmHg vs .(96-43 ± 9-14 ) mmHg] , TC [ (5-18 ± 0-91 ) mmol／L vs-(5-65 ± 1-03 ) mmol／L ] , LDL-C [ (3-00 ± 0-68 ) mmol／L vs-(3-24 ± 0-72 ) mmol／L ] ,serum creatinine SCr [ (110-71 ± 52-39 ) μmol／L vs-(138-52 ± 63-65) μmol／L] ,serum uric acid SUA [ (318-73 ± 102-62) μmol／L vs-(354-28 ± 108-35) μmol／L] , and significant reduction in level of HDL-C [ (1-19 ± 0-32) mmol／Lvs-(1-09 ± 0-30) mmol／L] in elevated AP-WV group , P＜0-05 or ＜0-01- Multi-factor Logistic regression analysis indicated that age ,diabetes mellitus ,SBP , TC ,SCr and EH stage were independent risk factors for APWV (OR＝2-826 －3-732 , P＜0-05 all).Conclusion :Age ,diabetes mellitus ,SBP ,TC ,SCr and EH stage are risk factors for APWV in EH patients- Therefore ,corre- sponding preventive and therapeutic measures should be taken to improve prognosis .

Combined gastroscopic and choledochoscopic transabdominal nasobiliary drainage / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Common bile duct (CBD) stones are a frequent problem in Chinese populations, and their incidence is particularly high in certain areas (Wang et al., 2013). In recent years, laparoscopic common bile duct exploration (LCBDE) and endoscopic retrograde cholangiopancreatography (ERCP) have been the main surgical procedures for CBD stones, although each has different advantages and disadvantages in the treatment of choledocholithiasis (Loor et al., 2017; Zhou et al., 2017). For patients with large stones, a dilated CBD, especially concurrent gallstones, LCBDE is the preferred and most economical minimally invasive procedure (Koc et al., 2013). However, a T-tube is often placed during LCBDE to prevent postoperative bile leakage; this is associated with problems such as bile loss, electrolyte disturbance, and decreased gastric intake (Martin et al., 1998). In addition, the T-tube usually must remain in place for more than a month, during which time the patient's quality of life is seriously compromised. Many skilled surgeons currently perform primary closure of the CBD following LCBDE, which effectively speeds up rehabilitation (Hua et al., 2015). However, even in sophisticated medical centers, the incidence of postoperative bile leakage still reaches ≥10% (Liu et al., 2017). Especially for a beginner, bile leakage remains a key problem (Kemp Bohan et al., 2017). Therefore, a safe and effective minimally invasive surgical approach to preventing bile leakage during primary closure of the CBD after LCBDE is still urgently needed.

The Bone Defect Repairment in Vivo with Co-cultured EPCs and BMSCs / 昆明医科大学学报

Objective To reconstruct the deformity of appearance and function of patients with bone defect, co-cultured system with two stem cells were combined with partial deproteinized biological bone to reconstruct the defect of tibia which is one of the main weight-bearing bone. Methods The bone marrow and peripheral blood were harvested form 18 New Zealand rabbits to isolated bone marrow stem cells and epithelial progenitor cells, and engineering bone was constructed with co-cultured system with these two stem cells and partial deproteinized biological bones; about 1 CM of bone defect of each rabbit was made with bone rongeur, then engineering bones were transplanted into the defect area, the osteogenesis and bone defect recovery were observed on day 14, 28 and month 2.Results The difference of absorbance values of BMSCs group, co-cultured cell group and blank group at each time point and between groups were all statistically significant (P＜0.001), and the collagen content of bone tissue increased gradually after implantation of tissue engineered bone, and the difference between each group was statistically significant (P ＜0.001). The repairment of bone defect with the PDPBB combined with BMSCs and EPCs system has the strongest ability to repair the structure andfunction of the tibial defect area. Conclusion The engineering bone constructed with two stem cells and partial deproteinized bone is a good material for bone defect reconstruction.

High-resolution melting-based TILLING of γ ray-induced mutations in rice / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Targeting Induced Local Lesions IN Genomes (TILLING) is a reverse genetics strategy for the high-throughput screening of induced mutations. γ radiation, which often induces both insertion/deletion (Indel) and point mutations, has been widely used in mutation induction and crop breeding. The present study aimed to develop a simple, high-throughput TILLING system for screening γ ray-induced mutations using high-resolution melting (HRM) analysis. Pooled rice (Oryza sativa) samples mixed at a 1:7 ratio of Indel mutant to wild-type DNA could be distinguished from the wild-type controls by HRM analysis. Thus, an HRM-TILLING system that analyzes pooled samples of four M2 plants is recommended for screening γ ray-induced mutants in rice. For demonstration, a γ ray-mutagenized M2 rice population (n=4560) was screened for mutations in two genes, OsLCT1 and SPDT, using this HRM-TILLING system. Mutations including one single nucleotide substitution (G→A) and one single nucleotide insertion (A) were identified in OsLCT1, and one trinucleotide (TTC) deletion was identified in SPDT. These mutants can be used in rice breeding and genetic studies, and the findings are of importance for the application of γ ray mutagenesis to the breeding of rice and other seed crops.

The Correlation Analysis between Hyperuricemia and Dyslipidemia in Rural Areas,Yunnan Province / 昆明医科大学学报

Objective To provide evidence－based prevention of chronic disease and nutritional interventions by investigating the development of dyslipidemia and hyperuricemia in rural areas of Yunnan and analyzing the relationship between hyperuricemia and dyslipidemia. Methods The cross－sectional study recruited 513 residents over 18 years old in 2016. The morning fasting venous blood of all subjects were obtained to detect uric acid, serum total cholesterol (TC), triglycerides (TG) and high－density lipoprotein cholesterol (HDL－C) . Each food factor's blood lipid to the hyperuricemia was determined through multivariate logistic regression. Results The prevalence rates of hyperuricemia and dyslipidemia were 18.7% and 44.7% respectively. Females were more likely to have hyperuricemia than males (P＜0.05) . Males were more likely to develop dyslipidemia than females (P＞0.05) . The prevalence of hyperuricemia and dyslipidemia increased with age. Logistic regression analysis showed that the level of TG and LDL－C were risk factors and the level of HDL－C was protective factor of hyperuricemia. Conclusion Regularly testing the levels of uric acid and blood lipid, enhancing the knowledge of reasonable diet and developing healthy dietary habits have significant importance to prevent chronic diseases.

Expression and Clinical Significance of mPGES-1 and NF-κB p65 in Diffuse Large B Cell Lymphoma / 中山大学学报(医学科学版)

[Objective]Examine the expression of microsomal prostaglandin E synthase-1(mPGES-1)and nuclear transcription factor kappa B p65(NF-κB p65)in diffuse large B cell lymphoma(DLBCL),assessing their correlation with clinical variables,prognosis and potential clinical valve.[Methods]The immunohistochemistry was uesd to investigate the expression of mPGES-1 and NF-κB p65 in 83 DLBCL patiens'tissues.The relationship between these two proteins and the clinical variables and prognosis of these patients was evaluated.[Results]The high expression of mPGES-1 and NF-κB p65 were observed in 65.1%(54/83)and 73.5%(61/83)cases of DLBCL,respectively.The expression level of NF-κB p65 was positively correlated with mPGES-1 expression(P<0.05).The expression of these two proteins was found to be significantly associated with B cell lymphoma/leukemia-2 protein(BCL-2),higher expression of Ki67,higher lactate dehydrogenase (LDH),more extranodal lesions,advanced Ann Arbor stage and higher international prognostic index(IPI)score(P<0.05). In addition,NF-κB p65 was related with multiple myeloma oncogene 1(MUM1),pathological type(P<0.05). Both mPGES-1 and NF-κB p65 overexpression was correlated with worse overall survival(OS)while NF-κB p65 was an in-dependent prognostic factor for OS of DLBCL(P<0.05).[Conclusions]mPGES-1 and NF-κB p65 were highly expressed in DLBCL and closely linked with each other. The overexpression of mPGES-1 and NF-κB p65 was correlated with tumor progression and unfavorable prognosis in patients with DLBCL.

Treatment strategies of complex lesions in patients with acute Stanford type A dissection of important branches involvement / 中华外科杂志

Acute Stanford type A aortic dissection with important branches involved is more complex, could lead to organ malperfusion syndrome even organ failure. The understanding of pathological anatomy, classification, staging, and the pathophysiological change has increasingly mature, but not complete. In addition, the treatment strategy for complex lesions is diversified, some questions may not reach consensus. Fully understanding of the anatomical and pathophysiology is very important for surgeons to choose reasonable treatment strategy. As the rapid development of the basic research, imaging techniques and the concept of surgery procedures, the manage technique of Stanfrod type A dissection and branch vessels at the same time is getting seriously, the related issues also need further discussions.

Effects of shRNA Targeting mPGES-1 on Tumorigenicity of K562 Cells in Nude Mice In Vivo / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effects of shRNA targeting mPGES-1 on tumorigenicity of human acute leukemia K562 cells in nude mice in vivo and its mechanisms.</p><p><b>METHODS</b>For experiment 3 groups including KD group(expression of mPGES-1 in K562 cells was down-regulated by shRNA), CON (cells without any treatment) and NC group (cells treated with nonspecific-sequence shRNA) were set-up. Western blot was used to test the expression of β-catenin and cyclinD1 in cells. Then the cells of 3 groups were implanted into BALB/c nude mice subcutaneously to establish murine xenograft model. The growth state of the mice and the size of the xenograft tumor were recorded. HE staining was used to observe the morphology of xenograft tumor. Expressions of β-catenin and cyclinD1 in xenograft tumor were detected by immunohistochemical staining.</p><p><b>RESULTS</b>In vitro the expression of β-catenin and cyclinD1 in KD group were lower than the CON group and NC group (P<0.05). In vivo the tumor volume and weight of KD group were significant smaller than the other two groups (P<0.01). HE staining showed that tissues in the KD group were relatively looser in arrangement with smaller cell nucleus and less cytoplasm. The expression of β-catenin and cyclinD1 in the KD group were remarkable weak as compared with that in CON group and NC group (P<0.05).</p><p><b>CONCLUSION</b>Down-regulating the expression of mPGES-1 by shRNA may significantly inhibit the tumorigenicity of K562 cells in nude mice in vivo and its mechanism may be related with the inhibition of expression of β-catenin and cyclinD1.</p>

Research on Relation of Platelet Aggregation Rate with Platelet Concentration in Platelet-Rich Plasma' / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the effect of platelet concentration in platelet-rich plasma (PRP)' on platelet aggregation rate, to determine the allowed range of inducer adenosine diphosphate (ADP: 5.0 µmol/L, ADP: 1.5 µmol/L) and arachidonic acid (AA: 500.0 µg/ml) for platelet concentration in platelet aggregation rate.</p><p><b>METHODS</b>The venous blood samples of 72 healthy persons with citrate anticoagulation were selected and divided into groups, every 12 cases were mixed for each group. After the samples were mixed, different levels of platelet concentrations were prepared, and platelet aggregation rate of 6 groups with different platelet concentrations by ADP and AA inducer were detected by Helena platelet aggregation analyzer respectively.</p><p><b>RESULTS</b>When the concentration of the inducer increased, the platelet aggregation rate of different platelet concentrations increased. With the platelet concentration increased, AA and ADP (15 µmol/L) induced platelet aggregation rate showed a rapid increase at first and then showed slowing, when the Plt concentration is less than 200×10/L, AA induced platelet aggregation rate decreased with the steep drop, and ADP induced platelet aggregation rate increased slightly slowly along with platelet concentration increasing. When platelet count lower than 200×10/L and AA 500 µg/ml and ADP 15 µmol/L were used for induction, the changes of platelet aggregation rate of different concentrations of platelet was slow, less volatile and more stable.</p><p><b>CONCLUSION</b>When the platelet aggregation rate was detected, the appropriate platelet concentration of AA and ADP inducing agents should be greater than 200×10/L.</p>

Effect of pyrroloquinoline quinone on learning and memory ability of apolexis rats / 中国食品卫生杂志

Objective This study aimed to investigate the role of pyrroloquinoline quinone (PQQ) in repairing oxidative nerve cells,and to study the antioxidant capacity of PQQ on the oxidative damage of rats caused by apolexis,as well as the effects on learning and memory abilities of apolexis rats.Methods Oxidative damage of PC12 was induced by H2O2,and the repairing rate of PQQ on oxidative PC12 cells was tested by methylthiazolyldiphenyl-tetrazolium bromide assay kit.The 18-month-old male SD rats were administered PQQ (0,10,20,40 mg/kg).After 4 weeks,Morris water maze test was used to test the learning and memory ability.After 6 weeks,serum and brain tissue related indicators and antioxidant capacity were recorded.Results The survival rate of PC12 cells increased from 59.1％ to 90.5％ with 200 nmol/L PQQ.Compared with the apolexis model group,the latency of the PQQ group (20,40 mg/kg) was shortened in the Morris water maze experiment,the swimming distance was reduced,pass-through counts were increased,and the first secure platform pass-through was reduced.Meanwhile,the levels of malondialdehyde and lipofuscin in serum and brain tissue of PQQ group decreased,the levels of superoxide dismutase,glutathione peroxidase vitality,antioxidant capacity of PQQ group (20,40 mg/kg) were enhanced.Conclusion PQQ could repair the oxidative damage of nerve cells,and it was confirmed that PQQ could play the same antioxidant effect in body and brain,and increase the learning and memory ability of apolexis rats.

Construction of shRNA-Bmi-1 plasmid and its effect on proliferation of ECA109 cells / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the role of Bmi-1 gene in the proliferation of squamous carcinoma cells and whether the silencing Bmi-1 can inhibit the growth of squamous cell carcinomas cells.</p><p><b>METHODS</b>The expressions of Bmi-1 in primary cultured Fibroblasts, karatinocyte cell line Hacat,squamous carcinoma cell line A431, and ECA109 were detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. Recombinant plasmid inserted with Bmi-1 gene short hairpin RNA (shRNA) expression vector PGPU6/GFP/Neo-shBmi-1 was constructed and transfected into ECA109 cells with control set. After transfection for 48 and 72 hours,the mRNA and protein levels of Bmi-1 were examined with RT-PCR and Western blot analysis, respectively. The proliferation of the ECA109 cells was evaluated by MTT method and flow cytometry.</p><p><b>RESULTS</b>Bmi-1 was highly expressed in A431 and ECA109 cells than in Fibroblast cells and Hacat cells. The mRNA and protein expressions of Bmi-1 were significantly silenced in ECA109 cells after recombinant expression vector PGPU6/GFP/Neo-shBmi-1 transfection (P<0.05). Compared with the control groups,the proliferation of ECA109 transfected with PGPU6/GFP/Neo-shBmi-1 was significantly inhibited (P<0.05), and cells in G1 phase increased while in S phase decreased (P<0.05).</p><p><b>CONCLUSIONS</b>Bmi-1 is involved in the proliferation of squamous carcinoma cells. After the silencing of Bmi-1 expression,the proliferation ECA109 cells is suppressed due to the altered cell cycle.</p>

The development and clinical application of facial minimally invasive fat granules injection device with controlled pressure and quantity / 中华整形外科杂志

<p><b>OBJECTIVE</b>To develop and evaluate the application of the facial minimally invasive fat granules injection device with controlled pressure and quantity.</p><p><b>METHODS</b>Due to the requirement of facial fat grafting (small volume, precision, high pressure), we developed the integrated device with handheld controller and motor. From Nov. 2013 to Mar. 2015, 50 cases who underwent facial fat transplantation were selected to receive facial fat grafting with the device on the right side and with conventional syringe on the left side as control. The clinical effect was assessed by patients, surgeon and one from the third party. The intraoperative pain, injection difficulty, postoperative swelling and hruising, complications and overall satisfactory were recorded. Pain intensity was assessed using digital classification method ( NRS). Therapeutic effect was evaluated using Likert 5 points scoring method. Chi-square test, Wilcoxon test and one-way ANOVA were used for statistical analysis.</p><p><b>RESULTS</b>The device has the advantages of minimal designed and easily handling. The injection speed is 7.2 mm/s with the fat injection volume as precise as 0.04 ml/s (0.0056 m/mm). Among the 50 cases, the excellent and good effect were achieved in 90% (45/50) on the right face, and 78% (39/50) on the left face (Z = -4.285, P < 0.01). Local nodes happened in 7 cases on left face, while none on the right face (χ² = 6.57, P < 0.05). Petechiae occurred in 21 cases on right face and 45 cases on left face (χ² = 5.37, P < 0.05). Pain was assessed as 3.7 ± 1.1 points on the right sides, and 5.2 ± 0.7 points on the left sides (F = 17.405, P < 0.01).</p><p><b>CONCLUSIONS</b>The facial minimally invasive fat granules injection device with controlled pressure and quantity has the advantages of easily handling, precisely controlled quantity with hotter effect, less pain and complication.</p>

Considerations for design and evaluation of clinical similarity comparison trial of biosimilars / 中国药学杂志

OBJECTIVE: To discuss the key considerations and evaluation criteria in designing a clinical comparison study to assess the clinical similarity of biosimilars. METHOD: Relevant guidelines and literatures on clinical similarity evaluation were reviewed, the cases were analyzed, discussions were carried out with biotech industry sponsors and clinical and statistical experts, the key considerations and evaluation criteria were proposed for assessing the clinical similarity of biosimilars. RESULTS AND CONCLUSION: The clinical similarity criteria should reflect the characteristics of the biological products. It is critical to select right patient population, clinical endpoints and equivalence/non-inferiority margin for development of different biosimilar products on the basis of fully understanding the quality, efficacy and safety profile of the original biological products. To set up the clinical similarity criterion and selection of the equivalence/non-inferiority margin, the consistency of the therapeutic effect of the reference product and subject variability need to be taken into consideration for robust evaluation of clinical similarity.

Clinical research of medicinal vesiculation for perennial allergic rhinitis / 中国针灸

<p><b>OBJECTIVE</b>To compare the efficacy differences between dog-days medicinal vesiculation and regular-day medicinal vesiculation for perennial allergic rhinitis (PAR), and observe their effects on serum immune globulin E (IgE) and interleukin-4 (IL-4).</p><p><b>METHODS</b>Seventy-two patients were randomly divided into a dog-days moxibustion group (34 cases) and a regular-day moxibustion group (38 cases). In the dog-days moxibustion group, medicinal vesiculation was applied on the 1st dog-day, 2nd dog-day and last dog-day in summer by lunar calendar, 3 treatments per dog-day for totally 9 times. In the regular-day moxibustion group, the moxibustion was given on the regular day for continuous 9 times. The symptom score, rhinoconjunctivitis quality of life questionnaire (RQLQ) and the level of IgE and IL-4 were compared before and after treatment in two groups; the short-term and two-year efficacy evaluation were performed too.</p><p><b>RESULTS</b>The short-term total effective rate was 88.2% (30/34) in the dog-days moxibustion group, which was not significantly different to 86.8% (33/38) in the regular-day moxibustion group (P>0.05). The long-term total effective rate was 97.1% (33/34) in the dog-days moxibustion group, which was significantly superior to 81.6% (31/38) in the regular-day moxibustion group (P<0.05). After treatment, the serum IgE, IL-4 and RQLQ were significantly reduced (all P<0.01), but the difference between two groups was not significant (all P>0.05).</p><p><b>CONCLUSION</b>Medicinal moxibustion could be taken as a regular treatment for PAR, which could be performed during the whole year, and dog-days moxibustion could be considered as an enhanced method for prevention and treatment of PAR.</p>

Effects of arsenic trioxide combined with bortezomib on proliferation and apoptosis of K562 cells and their mechanism / 中国实验血液学杂志

This study was aimed to investigate the effect of arsenic trioxide (As(2)O(3)) alone and in combination with bortezomib (Bor) on proliferation and apoptosis of leukemia cell line K562, and to analyze the potential mechanism. K562 cells were treated with different concentrations of As(2)O(3) or Bor (alone or combination) for 24, 48 h. MTT method was used to detect the cell proliferation. After K562 cells were treated with 0.5 µmol/L As(2)O(3) alone or in combination with 10 nmoL/L Bor, the apoptosis rate and cell cycle were measured by flow cytometry, and the activity of NF-κB was analyzed by SP immunohistochemistry. The results indicated that the different concentrations of As(2)O(3) and Bor could inhibit the K562 cell proliferation in a time- and dose-dependent manners (P < 0.05). The IC(50) of Bor and As(2)O(3) in 48 h were 20 nmol/L and 0.6 µmol/L respectively. When K562 cells were treated with As(2)O(3) or Bor alone for 24 h, the apoptotic rate of K562 cells increased, and the apoptotic rate in combination group was higher than that in As(2)O(3) or Bor group. The cells were apparently arrested in G(2)/M phase in Bor group and G(0)/G(1) phase in As(2)O(3) group. The activity of NF-κB decreased significantly in As(2)O(3) or Bor group (P < 0.05), this effect was most significant in the combination group (P < 0.01). It is concluded that both As(2)O(3) and Bor can inhibit the proliferation and induce apoptosis of K562 cells, a synergistic effect can be observed when a low dose of As(2)O(3) combined with low dose of Bor. The different cell cycle block site and the decrease of activity of NF-κB may be one of the mechanisms underlying their synergic effect.

Protective effects of human bone marrow mesenchymal stem cells on hematopoietic organs of irradiated mice / 中国实验血液学杂志

The objective of this study was to explore the protective effects of human bone marrow mesenchymal stem cells (MSC) on hematopoietic organs of irradiated mice. Human bone marrow MSC were isolated, ex vivo expanded, and identified by cell biological tests. Female BALB/c mice were irradiated with (60)Co γ-ray at a single dose of 6 Gy, and received different doses of human MSC and MSC lysates or saline via tail veins. The survival of mice was record daily, and the femurs and spleens were harvested on day 9 and 16 for pathologic examination. The histological changes were observed and the cellularity was scored. The results showed that the estimated survival time of MSC- and MSC lysate-treated mice was comparable to that of controls. The hematopoiesis in the bone marrow of mice that received high-dose (5×10(6)) of MSC or MSC lysates was partially restored on day 9 and the capacity of hemopoietic tissue and cellularity scorings were significantly elevated as compared with that of controls (P < 0.05). Proliferative nudes were also obviously observed in the spleens of mice that received high-dose of MSC or MSC lysates on d 9 after irradiation. The histological structures of the spleen and bone marrow of the mice that received high-doses (5×10(6)) of MSC or MSC lysates were restored to normal, the cell proliferation displayed extraordinarily active. Further, the cellularity scores of the bone marrow were not significantly different between the high-dose MSC and MSC lysate-treated mice. It is concluded that the bone marrow MSC can promote the hematopoietic recovery of the irradiated mice, which probably is associated with the bioactive materials inherently existed in bone marrow cells.