等毒性剂量芥子气诱导大鼠肺损伤炎性因子和蛋白表达变化

目的建立经腹腔和气管等毒性剂量(1LD_(50))芥子气(sulfur mustard,SM)诱导大鼠急性肺损伤模型,比较2种模型血清炎性因子水平和肺泡间隔相关蛋白表达的差异。方法选取Sprague Dawley大鼠,随机分为5组,采用ELISA和免疫组化法进行检测。结果 (1)腹腔SM组各时间段血清INF-γ、IL-23水平分别与气管SM组比较显著升高;血清IL-4水平腹腔SM组与气管SM组比较,差异有统计学意义。(2)腹腔SM组大鼠肺泡间隔各时间的NF-Kβ1,NF-Kβp65,ERK,JNK,p38MAPK蛋白阳性表达率分别与气管SM组比较显著升高。结论 SM(1LD50)诱导大鼠急性肺损伤,经腹腔注射血清炎性因子水平和肺泡间隔相关蛋白表达均明显高于经气管灌注,提示SM诱导的肺炎性反应与染毒途径有关。

等毒性剂量芥子气不同途径诱导大鼠急性肺损伤的氧化应激反应差异探讨

目的通过建立大鼠经腹腔和气管途径等毒性剂量(1LD50)芥子气(SM)急性肺损伤模型,比较2种肺损伤模型氧化应激反应的差异性。方法选取Sprague Dawley大鼠,随机分为腹腔SM组,腹腔丙二醇组,气管SM组,气管丙二醇组,正常组。采用酶联免疫吸附法和免疫组化法,检测血清酶和肺泡间隔相关蛋白表达。结果大鼠腹腔SM组血清各时间点超过氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)水平均高于同时点气管SM组(P<0.05);腹腔SM组肺泡间隔各时间点铜锌超过氧化物歧化酶(CuZn-SOD)、锰超过氧化物歧化酶(Mn-SOD)、对氧磷酶-1(PON-1)、载脂蛋白-1(ApoA1)表达的阳性细胞亦均高于气管SM组(P<0.05)。结论暴露SM(1LD50)后,2种大鼠急性肺损伤模型在分子水平氧化应激反应存在着差异性,提示等毒性剂量SM所致大鼠的氧化应激反应与染毒途径相关,并为抗氧化剂的应用提供了重要的理论依据。

基于发光细菌法的农产品中主要重金属的联合毒性评价

通过细菌发光抑制试验,研究Pb^(2+)、Cd^(2+)和Hg^(2+)的单一毒性,以及Pb^(2+)+Cd^(2+)、Cd^(2+)+Hg^(2+)、Pb^(2+)+Hg^(2+)、Pb^(2+)+Cd^(2+)+Hg^(2+)的混合毒性,分别采用等毒性单位法与加和指数法,对其混合物的联合毒性进行评价。结果表明,3种重金属的毒性大小为Hg^(2+)>Pb^(2+)>Cd^(2+)。对于混合体系,两种评价方法结果一致,即Pb^(2+)+Cd^(2+)为协同作用;Cd^(2+)+Hg^(2+)、Pb^(2+)+Hg^(2+)和Pb^(2+)+Cd^(2+)+Hg^(2+)均为拮抗作用。

Response of porcine hepatocytes in primary culture to plasma from severe viral hepatitis patients

AIM： To observe the effects of plasma from patients with severe viral hepatitis （SVHP） on the growth and metabolism of porcine hepatocytes and the clinical efficiency of bioartificial liver device.METHODS： Hepatocytes were isolated from male porcines by collagenase perfusion. The synthesis of DNA and total protein, leakages of AST and LDH, changes in glutathione （GSH）, catalase and morphology of porcine hepatocytes exposed to SVHP were investigated to indicate the effect of plasma from patients with severe hepatitis on the growth, injury, detoxification, and morphology of porcine hepatocytes.RESULTS： The synthesis of DNA and protein was inhibited in the medium containing 100% SVHP compared to the controls. The leakages of LDH and AST increased in porcine hepatocytes following exposure to 100% SVHP for 5 h. The difference between 100% SVHP and 10% newborn calf serum （NCS） was significant in t-test （LDH： t = 24.552, P = 0.001; AST： t = 4.169, P = 0.014）. After exposure to SVHP for 24 h, alterations in GSH status were significant （F = 2.746, P〈0.05） between porcine hepatocytes in 100% SVHP and 10% NCS, but no alteration occurred in the culture medium after 48 h （F = 4.378, ,P〈0.05）. A similar profile was observed in catalase activity. Many round vacuoles were observed in porcine hepatocytes cultured in SVHR The membranes of these cells became indistinct and almost all the cells died on d 5.CONCLUSION： Plasma from patients with severe hepatitis inhibits the growth, injures membrane, disturbs GSH homeostasis and induces morphological changes of porcine hepatocytes, It is suggested that SVHP should be pretreated to reduce the toxin load and improve the performance of porcine hepatocytes in extracorporeal liver-support devices.

Changes of plasma fasting carnitine ester profile in patients with ulcerative colitis

AIM： To determine the plasma carnitine ester profile in adult patients with ulcerative culitis （UC） and compared with healthy control subjects. METHOD： Using ESI triple quadrupole tandem mass spectrometry, the carnitine ester profile was measured in 44 patients with UC and 44 age- and sex-matched healthy controls. RESULTS： There was no significant difference in the fasting free carnitine level between the patients with UC and the healthy controls. The fasting propionyl- （0.331 ± 0.019 vs 0.392 ± 0.017 μmol/L）, butyryl- （0.219 ± 0.014 vs 0.265 ± 0.012）, and isovalerylcarniUne （0.111 ± 0.008 vs 0.134 ± 0.008） levels were decreased in the UC patients. By contrast, the level of octanoyl- （0.147 ± 0.009 vs 0.114 ± 0.008）, decanoyl- （0.180 ± 0.012 vs 0.137 ± 0.008）, myristoyl- （0.048 ± 0.003 vs 0.039 ± 0.003）, palmitoyl- （0.128 ± 0.006 vs 0.109 ± 0.004）, palmitoleyl- （0.042±0.003 vs 0.031 ± 0.002） and oleylcarnitine （0.183 ± 0.007 vs 0.163 ± 0.007; P 〈 0.05 in all comparisons） were increased in the patients with UC. CONCLUSION： Our data suggest selective involvement of the carnitine esters in UC patients, probably due to their altered metabolism.

应用发光细菌法检测饲用抗生素单一及联合毒性的研究

以HgCl2为毒性参照,以等毒性配比法研究了饲用盐酸金霉素、吉他霉素、盐霉素和黄霉素对发光细菌的单一及联合毒性。结果表明：盐酸金霉素、吉他霉素、盐霉素、黄霉素对明亮发光杆菌的急性毒性EC50分别为9.21、146.13、4.24 mg/L和134.68 mg/L,发光细菌的相对发光强度（RLU）随着抗生素浓度的提高而降低,并分别在2~16、25~200、1~8 mg/L和25~200 mg/L范围内呈良好线性关系;多元饲用抗生素对发光细菌具有联合毒性的作用,吉他霉素与盐酸金霉素、盐霉素和黄霉素3种抗生素的二元组合对发光细菌的联合毒性表现为较强的协同作用,而盐酸金霉素、盐霉素和黄霉素两两分别组合对发光细菌的联合毒性表现为拮抗作用;三元及四元抗生素混合体系对发光细菌的联合毒性均表现为拮抗作用。

Structure of Macro- and Trace Elements Status Observed in Residents of Magadan Town

The authors aimed the study at examining macro- and trace elements content in elderly people of the 1 period of middle age （21-35） residing in Magadan town to assess the content of 25 trace elements in hair samples on individual and population levels by atom-emission spectrometry with inductively-bonded argon plasma. It turned out that the majority of surveyed subjects were characterized by deformation of element status demonstrated by excess and deficit of the basic essential elements of different degrees of manifestation. Deficit of Co （68% of surveyed people）, Mg （67%）, Ca （64%）, Cu （47%）, K （46%）, Zn （44%）, I （41%）, Na （33%）, P （27%） and Se （24%） was typical for female subjects as well as excess of Si （28%）, Zn （22%） and P （20%）. Male residents were characterized by deficit of Co （81%）, Ca （66%）, Mg （65%）, I （50%）, Cu （37%）, K and Na （27%） and excess of Zn （41%）. In individual cases it was noted excess concentration of nominally essential and toxic elements in both examined groups. They were： A1, As, Cd, Li, Ni, Pb, Sn, V and B. While analyzing of medians of chemical concentration it was stated reliable sex-related differences （P 〈 0.05）： content of Ca, Mg and Mn was higher in hair samples of women, and content of As, B, Cd, Cr, K, Li, Na, P, Pb and V, on the contrary, was higher in male samples.

A single mutation in the PBC loop of VP2 is involved in the in vitro replication of infectious bursal disease virus

To test whether amino acid mutations in the PBC and PHI loops of VP2 are involved in the replication and virulence of infectious bursal disease virus(IBDV), a pair of viruses, namely the moderately virulent IBDV(rG x-F9VP2) and the attenuated strain(rGt), were used. Residue mutations A222P(P_(BC)) and S330R(PHI), selected by sequence comparison, were introduced individually into r Gx-F9VP2 by using a reverse genetics system. In addition, the reverse mutation of either P222 A or R330 S was introduced into r Gt. The four modified viruses were then rescued and evaluated in vitro(CEF cells) and in vivo(SPF chickens). Results showed that A222 P elevated the replication efficiency of rG x-F9VP2 while P222 A reduced that of rG t in CEF cells. A mutation at residue 330 did not alter IBDV replication. In addition, animal experiments showed that a single mutation at either residue 222 or 330 did not significantly influence the virulence of IBDV. In conclusion, residue 222 in PBC of VP2 is involved in the replication efficiency of IBDV in vitro but does not affect its virulence in vivo, further facilitating our understanding of the gene-function of IBDV.

Light-triggered plasmonic vesicles with enhanced catalytic activity of glucose oxidase for programmable photothermal/starvation therapy

Glucose oxidase(GOx)-based nanotheranostic agents hold great promise in tumor starvation and its synergistic therapy. Self-assembled plasmonic gold vesicles(GVs) with unique optical properties, large hollow cavity, and strong localized surface plasmon resonance, can be used as multi-functional nanocarriers for synergistic therapy. Herein,GOx-loaded GVs(GV-GOx) were developed for light-triggered GOx release as well as enhanced catalytic activity of GOx, achieving programmable photothermal/starvation therapy. Under near-infrared laser irradiation, the GV-GOx generated strong localized hyperthermia due to plasmon coupling effect of GVs, promoting the release of encapsulated GOx and increasing its catalytic activity, resulting in enhanced tumor starvation effect. In addition, the high photothermal effect improved the cellular uptake of GV-GOx and allowed an efficient monitoring of synergistic tumor treatment via photoacoustic/photothermal duplex imaging in vivo. Impressively, the synergistic photothermal/starvation therapy demonstrated complete tumor eradication in 4 T1 tumorbearing mice, verifying superior synergistic anti-tumor therapeutic effects than monotherapy with no apparent systemic side effects. Our work demonstrated the development of a light-triggered nanoplatform for cancer synergistic therapy.