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Antigenotoxic potential of curcumin and carvacrol against malathion-induced DNA damage in cultured human peripheral blood and its relation to GSTM1 and GSTT1 polymorphism 姜黄素和香芹酚对马拉硫磷诱导的人外周血DNA损伤的抗遗传毒性及其与GSTM1和GSTT1多态性的关系
Pub Date : 2015-09-01 DOI: 10.1016/j.bgm.2015.02.002
Neeraj Kumar , Anita Yadav , Sachin Gulati , Kanupriya , Neeraj Aggarwal , Ranjan Gupta

The aerial application of malathion, a widely used organophosphate insecticide, has raised public concerns about its potential adverse health effects. We, therefore, studied the antigenotoxic potential of curcumin and carvacrol against malathion-induced DNA damage using sister chromatid exchange (SCE) as a biomarker of genotoxicity. To observe the antigenotoxic potential of curcumin and carvacrol, heparinized fresh blood from healthy individuals was treated with 30 μg/mL of malathion in the presence of curcumin and carvacrol. Curcumin at concentrations of 25 μg/mL and 50 μg/mL had significantly reduced (p < 0.05) the frequency of SCE as compared to malathion-exposed sample. Similarly, carvacrol showed significant (p < 0.05) antigenotoxic effect at concentrations of 2.5 μg/mL and 5.0 μg/mL against malathion. We also studied the effect of GSTT1 and GSTM1 on the genotoxicity of malathion and antigenotoxic potential of curcumin and carvacrol. We observed that there is a statistically significant (p < 0.05) reduction in the frequency of SCE in case of curcumin and carvacrol as compared to malathion, but we did not observe any significant relationship (p > 0.05) between GSTT1 and GSTM1 polymorphism and the genotoxicity of malathion and antigenotoxic potential of curcumin and carvacrol.

马拉硫磷是一种广泛使用的有机磷杀虫剂,其空中施用引起了公众对其潜在健康不良影响的担忧。因此,我们利用姐妹染色单体交换(SCE)作为遗传毒性的生物标志物,研究了姜黄素和香芹酚对马拉硫磷诱导的DNA损伤的抗原性潜力。为了观察姜黄素和香芹酚的抗原性,在姜黄素和香樟酚存在的情况下,用30μg/mL马拉硫磷处理来自健康个体的肝素化新鲜血液。与马拉硫磷暴露样品相比,浓度为25μg/mL和50μg/mL的姜黄素显著降低了SCE的频率(p<0.05)。同样,香芹酚在2.5μg/mL和5.0μg/mL浓度下对马拉硫磷表现出显著的(p<0.05)抗原毒性作用。我们还研究了GSTT1和GSTM1对马拉硫磷的遗传毒性以及姜黄素和香芹酚的抗原性的影响。我们观察到,与马拉硫磷相比,姜黄素和香芹酚的SCE频率在统计学上显著降低(p<0.05),但我们没有观察到GSTT1和GSTM1多态性与马拉硫磷的遗传毒性和姜黄素和香樟酚的抗原毒性潜力之间的任何显著关系(p>0.05)。
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引用次数: 6
Human platelet lysate enhances the proliferation of Wharton's jelly-derived mesenchymal stem cells 人血小板裂解物增强沃顿果冻间充质干细胞的增殖
Pub Date : 2015-09-01 DOI: 10.1016/j.bgm.2015.06.001
Andreas Ardhika Antoninus , Wahyu Widowati , Laura Wijaya , Dwi Agustina , Sugiarto Puradisastra , Sutiman B. Sumitro , M.Aris Widodo , Indra Bachtiar

This study was performed to elucidate the potential of human platelet lysate (huPL) as an alternative to xeno-free media for culturing mesenchymal stem cells (MSCs). In this work, Wharton's jelly-derived MSCs (WJ-MSCs; n = 5) were isolated, characterized, and cultured in huPL derived from type O platelets reconstituted with type AB platelet-poor plasma (huPL–ABO). WJ-MSCs from five donors were cultured under two different conditions [cell culture supplemented with 20% fetal bovine serum (FBS) and 0.250 mg/mL, 0.125 mg/mL, 0.063 mg/mL, and 0.031 mg/mL huPL]. Growth kinetics, cell surface markers, and in vitro differentiation potential toward the adipogenic, chondrogenic, and osteogenic lineages were evaluated. Our results indicate that WJ-MSCs cultured in the presence of huPL–ABO showed typical fibroblast-like morphology and had a significantly higher cell count (p < 0.05), compared with those cultured in FBS. Furthermore, results of immunophenotyping assay showed similar MSCs characteristics for both culture conditions. In addition, no significant differences were observed in the MSCs differentiation toward the adipogenic, chondrogenic, and osteogenic lineages. The optimal concentrations of huPL–ABO in the culture medium were 0.250 mg/mL and 0.125 mg/mL. Because of insignificant differences between the concentrations in terms of WJ-MSCs population doubling time, the concentration of 0.125 mg/mL was used in all comparisons between FBS and huPL–ABO. The average concentrations of insulin-like growth factor-1, platelet-derived growth factor-AB, vascular endothelial growth factor, and transforming growth factor-β1 in huPL–ABO were 287.89 pg/mg, 47,096.63 pg/mg, 150.93 pg/mg, and 74,817.76 pg/mg, respectively. huPL–ABO produced by this method was able to enhance the WJ-MSCs proliferation rate constantly and decrease the required time to reach confluence compared with the FBS culture condition.

本研究旨在阐明人血小板裂解物(huPL)作为培养间充质干细胞(MSC)的无异种培养基的替代品的潜力。在这项工作中,分离、表征了沃顿果冻衍生的MSCs(WJ MSCs;n=5),并在用AB型贫血小板血浆(huPL–ABO)重建的O型血小板衍生的huPL中培养。在两种不同条件下培养来自五个供体的WJ MSCs[补充有20%胎牛血清(FBS)和0.250 mg/mL、0.125 mg/mL、0.063 mg/mL和0.031 mg/mL huPL的细胞培养物]。评估了生长动力学、细胞表面标志物和向脂肪、软骨和成骨谱系的体外分化潜力。我们的结果表明,与在FBS中培养的细胞相比,在huPL–ABO存在下培养的WJ MSCs显示出典型的成纤维细胞样形态,并且具有显著更高的细胞计数(p<;0.05)。此外,免疫表型分析的结果显示,在两种培养条件下,MSCs的特征相似。此外,间充质干细胞向脂肪、软骨和成骨谱系的分化没有观察到显著差异。培养基中huPL–ABO的最佳浓度为0.250 mg/mL和0.125 mg/mL。由于WJ MSCs群体倍增时间方面的浓度差异不显著,因此在FBS和huPL–ABO之间的所有比较中均使用0.125 mg/mL的浓度。huPL–ABO中胰岛素样生长因子-1、血小板衍生生长因子AB、血管内皮生长因子和转化生长因子-β1的平均浓度分别为287.89、47096.63、150.93和74817.76。与FBS培养条件相比,该方法产生的huPL–ABO能够不断提高WJ MSCs的增殖率,并缩短达到融合所需的时间。
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引用次数: 23
Adequate stimulation of hematopoietic stem cell proliferation by a polyherbal formulation (EMSA eritin) leading to lymphocyte differentiation in BALB/c mice after radiation 多羟基制剂(EMSA eritin)对BALB/c小鼠辐射后淋巴细胞分化的造血干细胞增殖的充分刺激
Pub Date : 2015-09-01 DOI: 10.1016/j.bgm.2015.05.001
Mansur Ibrahim , Edi Widjajanto , M. Aris Widodo , Sutiman B. Sumitro

Radiotherapy is still an essential option for treatment of various stages of cancer. However, the irradiation administered would deplete the hematopoietic stem cells in the bone marrow, which would eventually decrease the number of lymphocytes and erythrocytes in the circulatory system. EMSA eritin is a polyherbal formulation that has the ability to stimulate erythropoiesis in mice after radiation therapy. Erythropoiesis is a complex mechanism involving the interaction of dozens of genes that may also be involved in other cellular process, such as lymphopoiesis. In this study, we elucidated the potential of EMSA eritin to stimulate other mechanisms, in addition to being an inducer of erythrocyte production. Bioinformatic analysis results indicated that the EMSA eritin formulation contains multiactive compounds that synergistically drive hematopoiesis and trigger lymphocyte differentiation. We then tested this prediction using an in vivo cell-culture system in a mice model. Experimental results suggested that EMSA eritin is able to induce hematopoietic stem cell proliferation and differentiate these cells into lymphocytes in BALB/c mice after sublethal radiation therapy. Moreover, the polyherbal formulation increased proliferation and survival of B and T lymphocytes in a dose-dependent manner. The results indicate that the polyherbal formulation is adequate to ameliorate both erythropoiesis and lymphopoiesis. The formulation thus appears very promising for treatment of patients following radiation therapy. However, this warrants further investigation.

放射治疗仍然是治疗癌症不同阶段的重要选择。然而,照射会耗尽骨髓中的造血干细胞,最终会减少循环系统中淋巴细胞和红细胞的数量。EMSA eritin是一种多羟基制剂,能够刺激放射治疗后小鼠的红细胞生成。红细胞生成是一种复杂的机制,涉及数十个基因的相互作用,这些基因也可能参与其他细胞过程,如淋巴细胞生成。在本研究中,我们阐明了EMSA eritin除了作为红细胞产生的诱导剂外,还具有刺激其他机制的潜力。生物信息学分析结果表明,EMSA eritin制剂含有协同驱动造血和触发淋巴细胞分化的多种活性化合物。然后,我们在小鼠模型中使用体内细胞培养系统测试了这一预测。实验结果表明,EMSA-eritin能诱导BALB/c小鼠亚致死性放疗后的造血干细胞增殖并分化为淋巴细胞。此外,多羟基制剂以剂量依赖的方式增加了B和T淋巴细胞的增殖和存活。结果表明,多羟基制剂足以改善红细胞生成和淋巴生成。因此,该制剂对于放射治疗后的患者的治疗似乎非常有希望。然而,这需要进一步调查。
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引用次数: 3
Effects of combined supplementation of vitamins C and E on the oxidative modification of low-density lipoprotein, soluble form of CD36, soluble vascular cell adhesion molecule-1, and nitrite/nitrate oxide levels in idiopathic nephrotic syndrome 联合补充维生素C和E对特发性肾病综合征低密度脂蛋白氧化修饰、可溶性CD36、可溶性血管细胞粘附分子-1和亚硝酸盐/一氧化氮水平的影响
Pub Date : 2015-09-01 DOI: 10.1016/j.bgm.2015.04.001
Omega Mellyana , Edi Dharmana , Hardhono Susanto , Nanan Sekarwana

This study aimed to investigate whether a combined supplementation of vitamins C and E was able to modify the oxidized low-density lipoprotein (ox-LDL), soluble form of CD36 (sCD36), soluble vascular cell adhesion molecule-1 (sVCAM-1), and nitrite/nitrate oxide (NOx) levels in pediatric nephrotic syndrome (NS) cases. The study included 36 children with NS. The patients were randomly allocated to either the treatment group or the placebo group (18 children each). The treatment group received a combined supplementation of vitamins C and E. The serum levels of ox-LDL, sCD36, and sVCAM-1 were assayed by enzyme-linked immunosorbent assay. The serum levels of NOx were assayed by colorimetric assay. Results showed that the levels of ox-LDL, sVCAM-1, and NOx were decreased after treatment with a combined supplementation of vitamins C and E, but there was no statistical difference (p > 0.05). After treatment, there was an increase in the level of sCD36 in both groups, although this was not significantly different (p > 0.05). The level of ox-LDL was significantly lower in the remission-idiopathic NS (remission-INS) group compared with the nonremission-INS group (p < 0.05). The levels of ox-LDL and sVCAM-1 were significantly lower in the remission-treated group than in the nonremission-treated group (p < 0.05). In conclusion, the combined supplementation of vitamins C and E cannot modify the ox-LDL, sCD36, sVCAM-1, and NOx levels in children with INS. In remission cases, the combined supplementation of vitamins C and E reduces the ox-LDL and sVCAM-1 levels.

本研究旨在研究联合补充维生素C和E是否能够改变儿童肾病综合征(NS)患者的氧化低密度脂蛋白(ox-LDL)、可溶性CD36(sCD36)、可溶性血管细胞粘附分子-1(sVCAM-1)和亚硝酸盐/硝酸盐氧化物(NOx)水平。该研究包括36名NS患儿。患者被随机分配到治疗组或安慰剂组(每组18名儿童)。治疗组接受维生素C和E的联合补充。通过酶联免疫吸附法测定血清ox-LDL、sCD36和sVCAM-1的水平。通过比色法测定血清NOx水平。结果显示,联合补充维生素C和E治疗后,ox-LDL、sVCAM-1和NOx水平降低,但无统计学差异(p>0.05)。治疗后,两组sCD36水平均升高,尽管这没有显著差异(p>0.05)。与非复发性INS组相比,缓解期特发性NS(缓解期INS)组的ox-LDL水平显著降低(p<0.05)。缓解期治疗组的ox-LDL和sVCAM-1水平显著低于非复发性治疗组(p<0.01)。总之,维生素C和E的联合补充不能改变INS儿童的ox-LDL、sCD36、sVCAM-1和NOx水平。在病情缓解的情况下,联合补充维生素C和E可降低ox-LDL和sVCAM-1水平。
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引用次数: 0
Protective effect of green tea against ovarian and endometrial apoptoses in rats treated with depot medroxyprogesterone acetate 绿茶对醋酸甲羟孕酮治疗大鼠卵巢和子宫内膜凋亡的保护作用
Pub Date : 2015-09-01 DOI: 10.1016/j.bgm.2015.04.002
Nora Veri , Fivi Aulia , Retty Ratnawati , Dwi Yuni Nur Hidayati , Noorhamdani Noorhamdani , Pande Made Dwijayasa

This study aimed to investigate whether an extract of green tea (GT) modulates the apoptotic, superoxide-dismutase (SOD), and endothelial-nitric-oxide-synthase (eNOS) levels in rats treated with depot medroxyprogesterone acetate (DMPA). Twenty-five female Wistar rats were divided into the following groups (n = 5 rats each): control group, received DMPA, DMPA plus GT extract at doses of 10.8 mg/day (DMPA + GT1), DMPA plus DMPA plus GT extract at doses of 21.6 mg/day (DMPA + GT2), and DMPA plus DMPA plus GT extract at doses of 43.2 mg/day (DMPA + GT3). The treatment with DMPA plus GT was performed for 4 weeks. The ovarian and endometrial apoptotic indices were significantly higher in the DMPA group compared with the untreated control group (p < 0.05). This increase was significantly (p < 0.05) attenuated by all dose treatments of DMPA plus GT. The DMPA significantly decreased the SOD (ovarian) and eNOS (endometrial) levels compared with the untreated group. The decrease in the SOD level was significantly attenuated by highest doses of the extract. The decrease in the eNOS expression was significantly attenuated by two highest doses of the extract. In conclusion, DMPA induces apoptosis of the ovary and endometrium. The GT extract prohibits the increase in ovarian apoptosis, at least in part by modulation of the SOD. In the endometrium, this effect may be due to the modulation of the eNOS expression. Therefore, this may provide a natural therapy for attenuating the ovaries and endometrial dysfunction found in DMPA users.

本研究旨在研究绿茶提取物(GT)是否调节储存型醋酸甲羟孕酮(DMPA)治疗大鼠的细胞凋亡、超氧化物歧化酶(SOD)和内皮一氧化氮合酶(eNOS)水平。25只雌性Wistar大鼠被分为以下组(每组n=5只):对照组,以10.8mg/天的剂量接受DMPA、DMPA+GT提取物(DMPA+GT1),以21.6mg/天剂量接受DMPA+DMPA+GT提取液(DMPA+GT2),以43.2mg/天剂量接受DMPA+DMPA+GT提取物(DMPA+GT3)。DMPA加GT治疗4周。与未治疗的对照组相比,DMPA组的卵巢和子宫内膜凋亡指数显著升高(p<0.05)。DMPA加GT的所有剂量治疗都显著减弱了这种升高(p>0.05)。与未治疗组相比,DMPA显著降低了SOD(卵巢)和eNOS(子宫内膜)水平。最高剂量的提取物显著减弱了SOD水平的下降。eNOS表达的降低被两个最高剂量的提取物显著减弱。总之,DMPA可诱导卵巢和子宫内膜细胞凋亡。GT提取物至少部分通过调节SOD来抑制卵巢细胞凋亡的增加。在子宫内膜中,这种作用可能是由于eNOS表达的调节。因此,这可能为减轻DMPA使用者的卵巢和子宫内膜功能障碍提供一种自然疗法。
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引用次数: 5
Antidiabetic effects of Eugenia jambolana in the streptozotocin-induced diabetic male albino rat 大白桦对链脲佐菌素诱导的糖尿病雄性白化大鼠的降糖作用
Pub Date : 2015-09-01 DOI: 10.1016/j.bgm.2015.08.001
Kishalay Jana, Tushar Kanti Bera, Debidas Ghosh

Presently, no satisfactory effective treatment is available to cure diabetes mellitus. Although synthetic drugs are used, there are several drawbacks. The attributed antihyperglycemic effects of many traditional plants are due to their ability for the management of diabetes mellitus. This study aimed to investigate the antidiabetic effect of the ethyl acetate fraction of the seed of Eugenia jambolana in streptozotocin-induced diabetic male albino rats. Diabetic rats were treated with this fraction at a dose of 200 mg/kg/d for 35 days. Potential antidiabetic mechanisms were investigated with blood glucose (short-term and long-term model), serum insulin, glycated hemoglobin, study of in situ end-labeling in pancreatic tissue, quantitative reverse transcription polymerase chain reaction, followed by western blotting study to assess the hepatic hexokinase-I gene expression, and in-vitro assessment of intestinal maltase and sucrase activity. Results showed a significant antihyperglycemic action in both short-term and long-term treatment schedules. Serum insulin and glycated hemoglobin levels were also recovered in the treated group in comparison with the untreated diabetic group (p < 0.05). In situ end-labeling study focused on the regeneration of pancreatic beta cells in the treated group. We also observed the correction of expression of the hepatic hexokinase-I gene after the treatment of the fraction in diabetic rats. Intestinal maltase and sucrase activities also displayed inhibition activity in the presence of ethyl acetate fraction. The antidiabetic activity of the fraction was compared with glibenclamide, a standard antidiabetic drug. The findings provide information about the antihyperglycemic activity of this fraction through gene regulation.

目前,还没有令人满意的有效治疗糖尿病的方法。虽然使用了合成药物,但也有一些缺点。许多传统植物的降糖作用是由于它们对糖尿病的管理能力。本研究旨在探讨金银花种子乙酸乙酯部位对链脲佐菌素诱导的糖尿病雄性白化大鼠的降糖作用。以200 mg/kg/d剂量给药糖尿病大鼠35 d。通过血糖(短期和长期模型)、血清胰岛素、糖化血红蛋白、胰腺组织原位末端标记研究、定量逆转录聚合酶链反应、western blotting研究肝脏己糖激酶- 1基因表达、肠道麦尔糖酶和蔗糖酶活性的体外评估来研究潜在的降糖机制。结果显示,在短期和长期治疗方案显著的降糖作用。与未治疗组相比,治疗组血清胰岛素和糖化血红蛋白水平也有所恢复(p <0.05)。原位末端标记研究的重点是治疗组胰腺β细胞的再生。我们还观察了该组分对糖尿病大鼠肝脏己糖激酶- 1基因表达的纠正作用。肠道麦芽糖酶和蔗糖酶活性在乙酸乙酯部分存在下也表现出抑制活性。将其与标准降糖药格列本脲的降糖活性进行比较。研究结果提供了有关该部分通过基因调控的抗高血糖活性的信息。
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引用次数: 19
Protective effect of green tea against ovarian and endometrial apoptoses in rats treated with depot medroxyprogesterone acetate 绿茶对醋酸甲孕酮治疗大鼠卵巢和子宫内膜凋亡的保护作用
Pub Date : 2015-09-01 DOI: 10.1016/J.BGM.2015.04.002
Nora Veri, Fivi Aulia, R. Ratnawati, D. Hidayati, Noorhamdani Noorhamdani, Pande Made Dwijayasa
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引用次数: 4
Effects of combined supplementation of vitamins C and E on the oxidative modification of low-density lipoprotein, soluble form of CD36, soluble vascular cell adhesion molecule-1, and nitrite/nitrate oxide levels in idiopathic nephrotic syndrome 联合补充维生素C和E对特发性肾病综合征低密度脂蛋白氧化修饰、可溶性CD36、可溶性血管细胞粘附分子-1和亚硝酸盐/一氧化氮水平的影响
Pub Date : 2015-09-01 DOI: 10.1016/J.BGM.2015.04.001
Omega Mellyana, E. Dharmana, H. Susanto, N. Sekarwana
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引用次数: 0
Adequate stimulation of hematopoietic stem cell proliferation by a polyherbal formulation (EMSA eritin) leading to lymphocyte differentiation in BALB/c mice after radiation 多草药制剂(EMSA erittin)充分刺激造血干细胞增殖,导致放射后BALB/c小鼠淋巴细胞分化
Pub Date : 2015-09-01 DOI: 10.1016/J.BGM.2015.05.001
Mansur Ibrahim, E. Widjajanto, M. A. Widodo, S. Sumitro
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引用次数: 3
Concomitant exposure to cigarette smoke and coal dust induces lung oxidative stress and decreases serum MUC5AC levels in male rats 在雄性大鼠中,同时暴露于香烟烟雾和煤尘可诱导肺氧化应激并降低血清MUC5AC水平
Pub Date : 2015-06-01 DOI: 10.1016/j.bgm.2014.10.001
Nia Kania , Bambang Setiawan , Edi Widjajanto , Nurdiana Nurdiana , M. Aris Widodo , H.M.S. Chandra Kusuma

This study aimed to investigate whether concomitant exposure to cigarette smoke and coal dust could activate the epidermal growth factor receptor (EGFR) for MUC5AC expression. Thirty-two male Wistar rats were divided into the following groups (n = 8 each): control group (C); exposed to cigarette smoke plus coal dust at doses of 6.25 mg/m3 (CS + CD1); 12.5 mg/m3 (CS + CD2); and 25 mg/m3 (CS + CD3). The duration of exposure was 21 days, 1 hour/day. Lung malondialdehyde level was analyzed colorimetrically. Serum EGF and MUC5AC expression were measured by ELISA. Expression of lung EGFR and MUC5AC were measured by a confocal laser scanning microscopy. The level of lung malondialdehyde was higher significantly in all doses of exposure compared with control group (p < 0.05). The level of serum EGF was significantly increased in CS + CD2 group compared with control group or CS + CD1 group. The expression of EGFR was not significantly different among all the treatment groups (p > 0.05). Serum MUC5AC levels were significantly lower in the two highest doses of coal dust compared with the control group. In conclusion, subchronic combined exposure to cigarette smoke and coal dust induces lung oxidative stress and inflammation and decreases serum MUC5AC level.

本研究旨在探讨同时暴露于香烟烟雾和煤尘是否会激活表皮生长因子受体(EGFR) MUC5AC的表达。32只雄性Wistar大鼠分为两组,每组8只:对照组(C);暴露于香烟烟雾加煤尘剂量为6.25 mg/m3 (CS + CD1);12.5 mg/m3 (CS + CD2);25 mg/m3 (CS + CD3)。暴露时间21天,1小时/天。用比色法分析肺丙二醛水平。ELISA法检测血清EGF和MUC5AC的表达。共聚焦激光扫描显微镜检测肺EGFR和MUC5AC的表达。与对照组相比,所有暴露剂量的肺丙二醛水平均显著升高(p <0.05)。与对照组和CS + CD1组相比,CS + CD2组血清EGF水平显著升高。各治疗组间EGFR表达差异无统计学意义(p >0.05)。与对照组相比,两个最高剂量煤尘组血清MUC5AC水平显著降低。综上所述,亚慢性联合暴露可引起肺氧化应激和炎症反应,降低血清MUC5AC水平。
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引用次数: 1
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Biomarkers and Genomic Medicine
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