RETRACTION: Dynamic Protective Effect of Chinese Herbal Prescription, Yiqi Jiedu Decoction, on Testis in Mice with Acute Radiation Injury

Objective A Chinese herbal prescription, Yiqi Jiedu (YQJD) decoction, is used for injuries caused by radiotherapy. This study aimed to investigate the dynamic protective effects of YQJD decoction in mice on radiation damage at different time points of the testis. Methods The 200 male Balb/c mice were randomly divided into 5 groups (blank, model, Anduolin, low-dose YQJD, and high-dose YQJD groups). Blank and model groups were all given stomach deionized water. Anduolin group and high and low dose of Chinese herb groups were treated with Chinese material medical decoction compound for 2 weeks before being irradiated. Except for the blank group, other groups were given whole-body one-time irradiation of 5.5 Gy 60Co gamma rays. Histopathology examination of testes was conducted on the 1st, 7th, 21st, and 35th day after irradiation, respectively. Indexes of sperm motility rate, sperm count, serum levels of testosterone (T), estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were also measured correspondingly. Result Compared to 1 day and 7 days after irradiation, most of the indexes, including testis index, sperm motility, and count, were decreased on the 21st and 35th day in all irradiated groups. However, compared with the model group, the indexes to assess sperm quality and the morphological structures of testis in low-dose and high-dose YQJD groups were significantly recovered on the 21st and 35th days. Additionally, reproductive hormones, including testosterone and estradiol, were recovered more in low-dose and high-dose YQJD groups on the 21st and 35th days. Conclusion The YQJD decoction is able to accelerate the recovery of sperm indexes, testosterone, and estradiol levels of sex hormones in mice after irradiation and demonstrated good protective effects on the testis.

Due to paucity of suitable animal models, it has been difficult to study the development of long-term intestinal complications following fractionated irradiation. We recently developed a model which allows multiple radiation exposures of a short segment of rat ileum without the need for repeated surgery. In the present series, this model was used to study the influence of shortening the total treatment time (accelerated fractionation) on development of radiation enteropathy. Male rats were orchiectomized and a short segment of distal ileum was transposed to the scrotum. Starting 3 weeks after surgery, the scrotum containing the intestinal segment was x-irradiated with 20 fractions of 2.8 Gy (total dose 56 Gy). Two fractionation schedules were compared: One fraction per day (total treatment time 26 days) and 3 fractions per day (total treatment time 7 days). Actuarial survival curves were obtained, and the degree of radiation injury was assessed 2, 8, and 26 weeks after the last radiation exposure using a semiquantitative histopathologic scoring system. There was no mortality from acute radiation injury in either treatment group. All animals of the 1-fraction/day group survived the observation period (26 weeks). In the 3-fraction/day group, there was significant mortality due to intestinal obstruction, and cumulative mortality at 26 weeks was 100%. Radiation injury, as assessed by the histopathologic scoring system, was also more pronounced in this group than in the 1-fraction/day group. We conclude that shortening the total treatment time significantly increases the severity of late intestinal complications. Our data are suggestive of an association between acute mucosal damage and chronic radiation injury of the small intestine.

Objective To investigate the radioresistant effects of pprI gene of Deinococcus radiodurans on BALB/c mice. Methods Male BALB/c mice in SPF level were applied for this work. The pEGFP-c1 plasmid and pEGFP-c1-pprI gene recombinant plasmid were transferred into anterolateral muscle of mice with in vivo electroporation technology. The mice were irradiated by 6 Gy 60Co γ-rays in whole body and the mortality of mice was observed within 30 days after irradiation. In addition, the mouse were irradiated with 4 Gy γ-rays and then the peripheral blood cell number, apoptosis rates of thymocyte cells, spleen cells and bone marrow cells were observed in the days of 1, 7, 14, 28 and 35 after irradiation while the histopathological changes of lung and testis were observed in the days 7 and 28 after γ-ray irradiation. Results The highest gene transfection efficiency of muscle cells was obtained in a Plasmid injection amount of 50 μg/50 μl and electric field strength of 200 V/cm. The acute radiation mortality of pEGFP-c1-pprI gene recombinant plasmid transfer group was 30%, lower than that of irradiation group (60.0%) and pEGFP-c1 plasmid transfer group (63.3%) after 6 Gy γ-ray irradiation(χ2=4.90, 6.24, P<0.05). Compared with the irradiation group and pEGFP-c1 plasmid transfer group, the WBC count of pEGFP-c1-pprI gene recombinant plasmid group in peripheral blood of mice was significantly higher in the days of 1, 7, 14 and 28 (F=16.26, 8.10, 6.37, 10.74, P<0.05), PLT count was significantly higher in days of 7 and 14 (F=7.36, 5.71, P<0.05), meanwhile the lymphocyte percentage was increased significantly on the 7th day (F=18.43, P<0.05) after irradiation. On the other hand, the apoptosis rates of thymocyte cells and bone marrow cells were significantly decreased in the days of 1, 7, 14, 28 and 35 (F=3.88, 14.91, 14.14, 39.86, 5.65, P<0.05 and F=53.70, 11.75, 21.78, 41.40, 4.54, P<0.05) while the apoptosis rate of spleen cells was significantly decreased in the days of 1, 7, 14 and 28 (F=97.95, 56.61, 33.55, 14.71, P<0.05) after irradiation. Finally, the radiation histopathological changes of lung and testis of the pEGFP-c1-pprI gene recombinant plasmid group were slight and easy to recover. Conclusions Transfection of pprI gene of Deinococcus radiodurans by in vivo electroporation has significant protective effect on the acute radiation injury in BALB/c mice, which may have important clinical applications. Key words: Deinococcus radiodurans; pprI gene; BABL/c mice; In vivo electroporation; Acute radiation injury

Radiation injury of boron neutron capture therapy using mixed epithermal- and thermal neutron beams in patients with malignant glioma

To study the expressions of basic fibroblast growth factor (bFGF) and its receptor (bFGFR) in bone marrow of mice with acute radiation injury, and to evaluate the effect of Ligustrazine (Lt) on them. Fifty-six Kunming mice of clean grade were randomly divided into 3 groups, the normal group, the control group and the Lt group. Mice in the latter two groups were once homogeneously systemic irradiated with 6.0 Gy of 60Co, with the absorption dose rate of 0.56 Gy/min, then treated with saline (0.2 ml/mice) or Lt (2 mg/mice) respectively, twice a day through gastrogavage for successive 13 days. Mice were sacrificed in batch on the 3rd, 7th and 14th day by cervical dislocation to collect the bilateral femoral bone marrow for preparing bone marrow mono-nuclear cell (BMMNC) suspension. The bFGFR expression on surface of BMMNC was determined by flow cytometry; and the bFGF expression level in one side of femoral bone marrow tissue was detected by immunohistochemistry with SABC-AP assay. The bFGF expression in bone marrow of mice on the 3rd, 7th and 14th day after acute radiation injury all were significantly lower than that of the normal mice (P < 0.05 or P < 0.01). The expressions of bFGF and bFGFR in the Lt group detected were significantly higher than that in the control group detected at the corresponding time points (P < 0.05 or P < 0.01). By way of enhancing bFGF expression in bone marrow and bFGFR expression on surface of BMMNC to accelerate the repairing of homopoietic micro-environment in bone marrow might be one of the mechanisms of Lt in promoting hemopoietic function reconstitution after acute radiation injury.

Mesenchymal stem cells (MSCs) are a source of various multipotent stromal cells with low inherent immunogenicity. These cells can undergo multi-directional differentiation, support hematopoiesis, and regulate immune responses. MSCs can be easily collected and amplified. These cells can also be transfected using an exogenous gene. MSCs have been extensively applied in clinical treatments, such as in the therapy for acute radiation injury. This study was primarily performed to investigate the effect and mechanism of MSCs in acute radiation injury. Key words: Mensenchymal stem cell; Repair; Radiation injury

Background The testicular microcirculation was an important aspect of testicular physiology and it offered a stable environment for the transport of nutrients and secretary products in the testis. Yangjing capsule (YC), a traditional Chinese compound herbal prescription, has been proved as an effective drug to ameliorate spermatogenesis, promote testosterone synthesis in vivo, and cure spermatogenesis in clinical practice. Objective This study was aimed at understanding the potential mechanisms of YC exerting angiogenic effects in the mouse spermatogenesis dysfunction model induced by cyclophosphamide (CP) and MLTC-1 cells. Materials and Methods Balb/c mice were randomly divided into five groups: control, CP, CP plus YC (630 mg/kg), CP plus YC (1260 mg/kg), and CP plus YC (2520 mg/kg). After 30 days, mice were sacrificed and the expressions of endothelial marker CD34+, angiogenic marker VEGFA, VEGFR1, VEGFR2, and eNOS in the testes of the mice were examined; moreover, Leydig cell line MLTC-1 cells were cultured and treated with different concentrations of YC extracts (YCE), and the expressions of VEGFA, VEGFR1, VEGFR2, and eNOS, as well as the secretion of NO, were evaluated. Results We observed that YC significantly increased the expressions of VEGFA, VEGFR1, VEGFR2, and eNOS in testes of CP-treated mice; moreover, YCE has led to increased expressions of VEGFA, VEGFR1, VEGFR2, and eNOS and secretion of NO in MLTC-1 in vitro. These data suggested that the YC might be an alternative treatment for the dysfunction of testicular microcirculation by promoting the angiogenesis in the testis.

Cytokine-based treatment was well applied to manage acute radiation injury in recentyears.Unfortunately,efficacy of single cytokine was reduced because of multiple organs severe injury causedby hish dose irradiation.It is the rationale for cytokines combination.Anti.radiation efficacy of cytokinescombination were reviewed,especially hematopoietic growth factors and antiappoptic cytokines combined inacute radiation injury management were documented.Emergency cytokines combination would be analternative for acute radiation injury treatment. Key words: Radiation injuries; Cytokines; Hematopoietic growth factors

A Chinese herbal prescription Yiqi Jiedu decoction attenuates irradiation induced testis injury in mice

Umbilical cord mesenchymal stem cells (UC-MSCs) exert strong immunomodulatory effects and can repair organs. However, their roles in radiation injury remain unclear. We show that in tree shrews with acute radiation injury, injected UC-MSCs significantly improved survival rates, reduced lung inflammation and apoptosis, prevented pulmonary fibrotic processes, recovered hematopoiesis, and increased blood counts. A protein microarray analysis showed that serum levels of the anti-inflammatory cytokines IL-10 and IL-13 and the growth factors BMP-5, BMP-7, HGF, insulin, NT-4, VEGFR3, and SCF were significantly higher, while those of the inflammatory cytokines IL-2, TIMP-2, TNF-α, IFN-γ, IL-1ra, and IL-8 and the fibrosis-related factors PDGF-BB, PDGF-AA, TGF-β1, IGFBP-2, and IGFBP-4 were significantly lower in UC-MSC-injected animals. A transcriptome analysis of PBMCs showed that the mRNA expression of C1q was upregulated, while that of HLA-DP was downregulated after UC-MSC injection. These results confirm the immunohistochemistry results. eGFP-labeled UC-MSCs were traced in vivo and found in the heart, liver, spleen, lungs, kidneys, thymus, small intestine and bone marrow. Our findings suggest that UC-MSC transplantation may be a novel therapeutic approach for treating acute radiation injury.

Acute radiation damage caused by nuclear wars or nuclear power plant accidents is one of the major diseases that seriously threaten human health. Therefore, the development and application of radioprotectants have become the primary task in dealing with radiation threats. Hematopoietic growth factor plays an important role in inducing and promoting the proliferation and differentiation of hematopoietic cells. It is an effective strategy for the treatment of acute radiation syndrome. In recent years, the application of hematopoietic growth factor in the treatment of acute radiation injury has achieved satisfactory clinical efficacy and accumulated rich experience. However, the research on the treatment mechanism of acute radiation damage, the timing of the drug, the dose and the reasonable compatibility need to be further discussed and summarized. This paper reviews the current status and progress of this research. Key words: Hematopoietic growth factor; Acute radiation injury; Treatment

Acute radiation injury is one of serious complication of exposure to irradiation, but there is still no effective means to prevent and treat it. However, mesenchymal stem cells (MSCs) are self-renewal and differentiating into various cell lineages. These cells possess attributes such as secreting a variety of cytokines, anti-inflammatory and immunosuppressive properties. The advantages of MSCs in tissue-repaired is conspicuous, but the timing and doses of transplants have been controversial. The safety problems such as tumorigenicity restrict clinical trials. Recently, the result of cell-free transplantation is fruitful, and the new situation definitely comes soon. This review summarizes and discusses recent advances on MSCs treating severe acute radiation. Key words: Mesenchymal stem cells MSCs; Radiation injury; Cell therapy

Metallothionein (MT), the synthesis of which can be induced by metalloelement administration, is a known radical scavenger. This study investigated the possible protective effect of MT against acute radiation injury. Manganese chloride (10 mg of manganese/kg) was administered intraperitoneally to male C3H/He mice 24 h prior to irradiation. The paw of each mouse was irradiated locally, and the acute skin reaction was scored daily and averaged. Acute radiation injury of the small intestine was studied using an LD50/8 assay and a gut microcolony assay after abdominal irradiation. An LD50/8 value represents the radiation dose required to kill 50% of animals within 8 days. The number of microcolonies per tissue section was counted 3.5 days after irradiation. The level of MT in the liver, skin and intestine was determined by a modified 203Hg-binding assay. Acute skin reaction was not prevented by manganese pre-administration. The LD50/8 values of manganese-pretreated and control mice were 19.4 and 18.4 Gy, respectively. However, the difference was not significant. The number of microcolonies was not significantly different for these two groups in the dose range of 13-19 Gy. The level of MT in the skin and intestine was not increased by administration of manganese, although a sixfold increase was observed in the liver. In conclusion, manganese chloride treatment of mice 24 h prior to irradiation did not significantly protect skin and small intestine against acute radiation injury, because such a treatment did not result in increased levels of MT in the skin and small intestine.

Objective To investigate the protective activity of Siwu Decoction against acute radiation injury. Methods The population of peripheral white blood cells (WBCs) and bone marrow nucleated cells, as well as the 30 d survival rate of mice were studied in accordance with the China Food and Drug Administration regulation on anti-radiation health food. Results Compared with the control group, mice treated with Siwu Decoction showed significantly increased peripheral WBCs, red blood cells, hemoglobin, platelets, and bone marrow nucleated cells. The 30 d survival rate increased in all administration groups of mice. Conclusion Siwu Decoction extract at recommended dose exerts protective activity against radiation injury. Key words: Radiation injuries; Hemopoietic system; Dietary supplements; Siwu Decoction

Objective To study the protective effect of pyrrolidine dithiocarbamate (PDTC) on acute irradiated mice. Methods The 6-8 weeks old male ICR mice were randomly divided into five groups: irradiation alone group (IR), positive control group (amifostine WR-2721 250 mg/kg) and PDTC of 30, 60 and 90 mg/kg dose groups. Each group had 10 mice and the drug was given at 0.5 h before whole body irradiation. At 30 d post-irradiation of 7.5 Gy 137Cs γ-rays, the mice survival were observed. At 8 d post-irradiation of 5.0 Gy 137Cs γ-rays, the peripheral blood, hematopoietic system and organ indexes were observed to evaluate the radiation protective effect of PDTC. Results PDTC increased the 30-day survival rates and 60 mg/kg dose had the most obvious effect by increase the survival to 60%(6/10). The survivals of irradiation alone group and the amifostine positive control group was 10%(1/10) and 70%(7/10), respectively. Compared with the irradiation alone group, 60 mg/kg PDTC group had the significant difference in spleen index, WBC, HGB, PLT, bone marrow nucleated cells and colony forming unit of spleen(t=2.354, 4.793, 2.342, 6.542, 2.649, 3.982, P<0.05). Conclusions PDTC is effective in radiation protection with an optimum dose of 60 mg/kg. Key words: Pyrrolidine dithiocarbamate; γ-rays; ICR mice; Radiation injury