去铁胺促进亚致死剂量X射线辐照小鼠的骨髓造血功能恢复

目的探讨去铁胺(DFO)对亚致死剂量X射线辐照C57小鼠骨髓造血功能的影响。方法将C57小鼠随机分成空白对照组、全身亚致死剂量辐照组(TBI组)、DFO治疗组(DFO组),每组10只。经5.4 Gy、1.0 Gy/min X射线全身辐照后,DFO组小鼠每天经皮下注射给予100 mg·kg-1 DFO溶液,其余各组小鼠皮下注射等量的生理盐水。每隔2 d称小鼠体质量,给药10 d后每组随机处理5只小鼠,检测血细胞计数、骨髓有核细胞计数、骨髓CD34+细胞比例及骨髓有核细胞中凋亡、铁死亡相关蛋白cleaved PARP-1、cleaved caspase-3、血管内皮生长因子(VEGF)、GPX4及SLC7A11的表达;给药20 d后处理每组剩余的5只小鼠,分别检测血细胞计数、骨髓有核细胞计数、骨髓病理学等。结果与空白对照组相比,TBI组和DFO组小鼠体质量在第3天明显降低(P<0.05),第6天TBI组小鼠体质量降至最低(P<0.01)。与空白对照组相比,在辐照后第10、20天TBI组小鼠血细胞计数、骨髓有核细胞计数明显降低(P<0.01或P<0.001),骨髓病理显示TBI组小鼠骨髓造血组织及有核细胞明显减少、出现脂肪空泡等,并且在辐照后第10天TBI组小鼠骨髓有核细胞中cleaved PARP-1和cleaved caspase-3蛋白表达明显增加(P<0.01),而GPX4、SLC7A11蛋白表达明显减少(P<0.05)。与TBI组相比,在辐照后第10天DFO组小鼠骨髓中CD34+细胞比例明显增加(P<0.001);骨髓中cleaved PARP-1和cleaved caspase-3蛋白表达明显降低(P<0.05),GPX4、SLC7A11蛋白表达明显增加(P<0.05),及骨髓微环境中VEGF表达增加(P<0.05);与TBI组相比,在辐照后第20天DFO组白细胞、红细胞、血小板、骨髓有核细胞计数明显升高(P<0.05或P<0.01),并且骨髓病理显示骨髓造血组织及有核细胞增加。结论DFO可能通过抑制骨髓有核细胞凋亡、铁死亡,并促进骨髓微环境中VEGF表达及CD34+细胞增殖来改善亚致死剂量辐照小鼠骨髓造血功能。

Investigation on the Appropriate Dose of ^(60)Co-γ Irradiation for Tubers of Purple Sweet Potato

[Objective] This study aimed to investigate the appropriate dose of 60^Co-γ irradiation for tubers of purple sweet potato.[Methods] The tubers of two purple sweet potato varieties Xuzi L-7 and Yuenanzi were used as experimental materials,and treated with 60^Co-γ irradiation at different doses（0,25,50,75,100,125 and 150 Gy） to determine the emergence rate,number of emerged seedlings per tuber and fresh weight per seedling.[Results] After the 60^Co-γ irradiation at different doses,the emergence period of tubers was postponed while the emergence rate,number of emerged seedlings per tuber and fresh weight per plant were decreased,and the differences between different varieties and different irradiation doses reached significance level.Compared with the control,the emergence period of tubers at irradiation doses above 25 Gy were postponed by 2,3,5,6 and 12 d,respectively.[Conclusion] The half lethal dose（LD50） of Xuzi L-7 was 66.73 Gy,and that of Yuenanzi was 74.96 Gy.

A novel derivative of xanomeline improved memory function in aged mice

Objective To characterize the function of a new xanomeline-derived M 1 agonist, 3-[3-（3-florophenyl-2-propyn- 1- ylthio）-1,2,5-thiadiazol-4-yl]-1,2,5,6- tetrahydro-1-methylpyridine Oxalate （EUK1001）, the acute toxicity and the effects on synaptic plasticity and cognition of EUK1001 were evaluated. Methods To examine the median lethal dose （LD50） of EUK1001, a wide dose range of EUK1001 was administered by p.o. and i.p. in aged mice. Furthermore, novel object recognition task and in vitro electrophysiological technique were utilized to investigate the effects of EUK1001 on recognition memory and hippocampal synaptic plasticity in aged mice. Results EUK1001 exhibited lower toxicity than xanomeline, and improved the performance of aged mice in the novel object recognition test. In addition, bath application of 1 μmol/L EUK1001 directly induced long-term potentiation in the hippocampus slices. Conclusion We conclude that EUK1001 can improve the agerelated cognitive deficits.

Plasma microRNA profiles distinguish lethal injury in acetaminophen toxicity: A research study

AIM: To investigate plasma microRNA (miRNA) profiles indicative of hepatotoxicity in the setting of lethal acetaminophen (APAP) toxicity in mice. METHODS: Using plasma from APAP poisoned mice, either lethally (500 mg/kg) or sublethally (150 mg/kg) dosed, we screened commercially available murine microRNA libraries (SABiosciences, Qiagen Sciences, MD) to evaluate for unique miRNA profiles between these two dosing parameters. RESULTS: We distinguished numerous, unique plasma miRNAs both up- and downregulated in lethally compared to sublethally dosed mice. Of note, many of the greatest up- and downregulated miRNAs, namely 574-5p, 466g, 466f-3p, 375, 29c, and 148a, have been shown to be associated with asthma in prior studies. Interestingly, a relationship between APAP and asthma has been previously well described in the literature, with an as yet unknown mechanism of pathology. There was a statistically significant increase in alanine aminotransferase levels in the lethal compared to sublethal APAP dosing groups at the 12 h time point (P < 0.001). There was 90% mortality in the lethally compared to sublethally dosed mice at the 48 h time point (P = 0.011). CONCLUSION: We identified unique plasma miRNAs both up- and downregulated in APAP poisoning which are correlated to asthma development.

Histopathological alterations in the liver and intestine of Nile tilapia Oreochromis niloticus exposed to long-term sublethal concentrations of cadmium chloride

Fingerlings of Nile tilapia Oreochromis niloticus were exposed to 1.68, 3.36, and 5.04 mg/L cadmium(as CdCl2), which represent 10%, 20%, and 30% of their previously determined 96-h LC5 0. After exposure for 20 days, sections of the liver and intestine of treated fish were examined histologically. Histopathological changes varied from slight to severe structural modification, depending on the exposure concentration. The hepatic tissues of fish exposed to 10% LC 50 showed markedly increased vacuolation of the hepatocytes and coarse granulation of their cytoplasm. Abundant erythrocytic infiltration among the hepatocytes was observed in fish exposed to 20% LC5 0. In the intestinal tissues of fish exposed to all doses, goblet cells proliferated and were greatly increased in size, the longitudinal muscularis mucosa was disturbed and, in the crypts of the sub-mucosal layer, apoptosis increased, indicated by large numbers of degenerated nuclei. Large numbers of inflammatory cells and dilated blood vessels were observed in the intestine of the group treated with 30% LC5 0.

新引进药用植物VUKA（Mondia whitei L.）对小鼠喂饲之安全性评估

For the purpose to investigate the safety of utilizing VUKA (Mondia whitei L.), we processed the acute oral toxicity test in ICR mice. There was no mouse dead after given with VUKA extracts during the time course, so the LD50 of water-extracted and freeze-dried powder of VUKA was estimated over 15 g/kg body weight for mice. No significant lesions of brain, heart, liver, kidney, spleen and thymus were found at gross and histopathological observation in the treated mice. Hematological parameters included of WBC, RBC, HGB, HCT, MCV, MCH, MCHC and PLT values were as normal as control. Besides, serum biochemistry changes in liver and renal function included of ALT, AST and creatinine values had no significant difference (p＞0.05) with control.

Effects of Sublethal Doses of Chlorfluazuron on Pupal-testis in the Common Cutworm, Spodoptera fitura （F,） （Lepidoptera： Noctuidae）

The effects of sublethal doses （LD10：1.00 ng larval-1; LD30： 3.75 ng larva-1） of chlorfluazuron on number and size of developmental spermatocytes in pupal-testis during spermatogenesis of the common cutworm, Spodoptera litura （F.） are described. Chlorfluazuron was applied topically to newly-ecdysed fifth-instar larvae of S. litura under laboratory conditions. During first day of pupation, spermatids were the highest （3,430 ± 7）, however, elongated spermatocytes with mature sperm were the lowest （292 ± 16） in number in pupal-testis compared with other developing spermatocytes. During last day of pupation, elongated spermatocytes with mature sperm were the highest （3,581 ± 3）, however, spermatogonia were the lowest （86± 4） in number in pupal-testis compared with other developing spermatocytes. The number of spermatogonia, primary and secondary spermatocytes, spermatids and elongated cysts with mature sperm were increased during pupal-developmental days in the controls. However, their numbers were significantly reduced in LD10- and even more significantly reduced in LD30-treated pupal-testis compared with controls. Moreover, eupyrene sperm bundles were not present in pupal-testis. During pupal-developmental days, spermatids were the smallest （4.1 ± 0.9 dm in μm） and secondary spermatocytes were the largest （31.0 ± 1.8 dm in μm） in size compared with other developing spermatocytes. The sizes of the same developing spermatocytes were significantly reduced in LD10-treated and more significantly reduced in LD30-treated pupal-testis of S. litura compared with controls.

Sublethal Irradiation Promotes Migration and Invasiveness of Prostate Cancer PC-3 Cells:Implications for Radiotherapy of Human Prostate Cancer

OBJECTIVE To study the changes in the matrix metalloproteinases-2 and 9 （MMP2, MMP9） induced by ^60Co γ-ray external irradiation of human prostate cancer PC-3 cells. METHODS Human prostate cancer PC-3 cells were irradiated with different doses of ^60Co γ-rays. Cell migration and invasiveness were evaluated and the expression of MMP2, and MMP9 was investigated by RT-PCR, Western blotting and flow cytometry（FCM）. RESULTS Irradiation enchances invasive protential at the doses of 1,3 and 5 Gy,whereas it significantly inhibits cell migration. CONCLUSION The different doses of ^60Co γ-ray external irradiation for prostate cancer may have different effects through the changes of MMP2, and MMP9 expression.

Effects of Sublethal Doses of Chlorfluazuron on Ovarioles in the Common Cutworm, Spodoptera Litura （F.） （Lepidoptera： Noctuidae）

Chlorfluazuron is an insect growth regulator for controlling the major insect pests in crops. This paper describes the effects of sublethal doses （LD10：1.00 ng/larva; LD30：3.75 ng/larva） of chlorfluazuron on ovarioles during ovarian development and oogenesis of common cutworm, Spodoptera litura （F.）. It is a significant pest of cotton, tobacco and miscellaneous vegetables. The LDlo or LD3o was applied topically to the newly-ecdysed fifth-instars of S. litura under laboratory conditions. In controls, on 2nd day of adult emergence, the cell density in germarium was 1636 ± 9.17 nuclei/mm^2. It increased until 3rd day, i.e., 1829 ± 8.87 nuclei/mm^2 and decreased thereafter. In the LDloor LD-3o-treated insects, the patterns of the cell density was the same as in controls but values were significantly （P 〈 0.05） decreased in the LD10- and more in the LDa0-treated females compared with controls. In control, ovaries were normal type and had mature ova with an occasional one or two being absorbed. In LD10-treated females, ovaries had spaces in ovarioles and absorption of ova. In LD30-treated females, besides the spacing and absorption, sometimes only immature （germarium） ova were found.

Effects of Chlorfluazuron Sublethal Doses on Spermatogenesis of Adult Common Cutworm, Spodoptera fitura （F.） （Lepidoptera： Noctuidae）

Chlorfluazuron is an insect growth regulator for controlling the major insect pests in crops. This paper describes the effects of sublethal doses （LD10：1.00 ng/larva; LD3o： 3.75 ng/larva） of chlorfluazuron on spermatogenesis in the adults of the common cutworm, Spodoptera litura （F.）. Chlorfluazuron was applied topically to the newly-ecdysed fifth-instars ofS. litura under laboratory conditions. The secondary spermatocytes, spermatids, elongated spermatocytes with mature sperm and eupyrene sperm bundles were present in testis of newly emerged, 1 and 2 day-old adults, but gradually decreased in their numbers in the controls. However, the spermatogonia were not present in newly emerged, 1 and 2 day-old adults. Moreover, primary spermatocytes were present （174 ± 4.0） in newly emerged adults, but not found in 1 and 2 day-old adults. In the testes of newly emerged LD10-treated adults, the numbers of eupyrene and apyrene sperm bundles were significantly reduced compared with controls, and even significantly reduced in LD30-treated adults compared with LDlo, however, their ratios were not affected. Moreover, the pattern of spermatogenesis was the same in LD10- and LD30-treated male adults compared with controls. Furthermore, numbers of developing spermatocytes were significantly reduced in the LD10 compared with controls, and even significantly reduced in LD30-treated male adults compared with LD10. In newly emerged adults, the width and length of elongated spermatocytes with mature sperm were significantly reduced in LDlo- and more significantly reduced in LD30-treated compared with controls of S. litura. In vas deferens of untreated pre- and newly emerged adult male, both eupyrene and apyrene sperm bundles were found, however, in treated pre-adult male, only apyrene sperm bundles and in treated newly emerged adult male, fe, w eupyrene and numerous apyrene sperm bundles were found. It is concluded that spermatogenesis was significantly affected by chlorfluazuron.