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[This corrects the article DOI: 10.1016/j.apsb.2022.09.003.].
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Radiation protection drugs are often accompanied by toxicity, even amifostine, which has been the dominant radio-protecting drug for nearly 30 years. Furthermore, there is no therapeutic drug for radiation-induced intestinal injury (RIII). This paper intends to find a safe and effective radio-protecting ingredient from natural sources. The radio-protecting effect of Ecliptae Herba (EHE) was discovered preliminarily by antioxidant experiments and the mouse survival rate after 137Cs irradiation. EHE components and blood substances in vivo were identified through UPLC‒Q-TOF. The correlation network of "natural components in EHE-constituents migrating to blood-targets-pathways" was established to predict the active components and pathways. The binding force between potential active components and targets was studied by molecular docking, and the mechanism was further analyzed by Western blotting, cellular thermal shift assay (CETSA), and ChIP. Additionally, the expression levels of Lgr5, Axin2, Ki67, lysozyme, caspase-3, caspase-8,8-OHdG, and p53 in the small intestine of mice were detected. It was found for the first time that EHE is active in radiation protection and that luteolin is the material basis of this protection. Luteolin is a promising candidate for RⅢ. Luteolin can inhibit the p53 signaling pathway and regulate the BAX/BCL2 ratio in the process of apoptosis. Luteolin could also regulate the expression of multitarget proteins related to the same cell cycle.
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Objective:To study the effect of fasting on 137Cs γ-ray radiation-induced intestinal injury in mice, and to explore the effect of fasting on fecal metabolites of mice through non-targeted metabolomics. Methods:C57BL/6 mice were divided into healthy control group, 9 Gy γ-ray whole body irradiation (WBI)/ 15 Gy γ-ray whole abdominal irradiation (WAI) group, fasting (24 h, 48 h, 72 h)+ 9 Gy WBI/ 15 Gy WAI group. After irradiation, the survival rate, spleen index and thymus index were calculated. C57BL/6 mice in non-target metabolism experiment were randomly divided into four groups: control group, fasting 24 h group, 15 Gy γ-ray WAI group, fasting 24 h + 15 Gy γ-ray WAI group, 6 mice in each group. After 15 Gy WAI, the feces of mice in each group were collected at 3.5 days for non-targeted metabolomics detection.Results:The median survival time of mice with 48 h and 24 h fasting before 9 Gy γ-ray irradiation was increased by 1 day and 4 days, and the survival rates of mice treated with 48 h and 24 h fasting before 15 Gy WAI were 16.67% and 25%, respectively. 15 Gy γ-ray WAI on mice with fasting for 24 h before irradiation could increase the body weight ( t=2.338, P=0.042) and spleen index ( t=2.289, P=0.045) at 3.5 days after irradiation. Through non-targeted metabonomic analysis, it was found that there were 30 differentially expressed metabolites in fecal samples of fasting and non-fasting mice subjected to WAI, and metabolic pathway enrichment analysis showed that there was an imbalance in the metabolic pathway of steroid biosynthesis. Conclusions:Fasting before irradiation can improve the survival rate of mice with intestinal radiation injury and change their intestinal metabolites, suggesting that pre-irradiation fasting or short-term dietary nutrition changes are involved in the regulation of intestinal radiation damage.
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Pyroptosis is a pattern of cell death to eliminate endogenous and exogenous harmful stimuli. GSDMD and GSDME, members of the Gasdermin protein family, are the main executors of pyroptosis, and after being cut by activated caspases, they can induce pyroptosis by perforating the cell membrane, and causing the release of intracellular inflammatory factors such as IL-18 and IL-1β. Recent studies have found that pyroptosis is involved and plays a "double-edged sword" role in the development and progression of liver diseases. This article elaborates on the molecular mechanism of pyroptosis and the research advances in the role of pyroptosis in the development and progression of liver diseases, so as to provide new targets and ideas for the prevention and treatment of liver diseases.
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Long-chain non-coding RNA (LncRNA) has more than 200 nucleotides in length and cannot encode proteins. It has a variety of biological functions. A large number of studies have shown that LncRNA is closely related to the occurrence and development of cancer. Researches at the level of molecular biology have found that LncRNA acts as an important regulatory molecule involved in the whole process of life activities and plays a regulatory role in various diseases and tumors. LincRNA-p21 is a novel LncRNA that acts as a translational inhibitor by targeting mRNA or by directing the chromatin site of a protein-binding partner. LincRNA-p21 is closely related to a variety of tumors and exerts its biological functions of carcinogenesis or tumor suppression through different pathways. In this paper, the research progress of the tumor-associated gene LincRNA-p21 was reviews
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Long-chain non-coding RNA (LncRNA) has more than 200 nucleotides in length and cannot encode proteins. It has a variety of biological functions. A large number of studies have shown that LncRNA is closely related to the occurrence and development of cancer. Researches at the level of molecular biology have found that LncRNA acts as an important regulatory molecule involved in the whole process of life activities and plays a regulatory role in various diseases and tumors. LincRNA-p21 is a novel LncRNA that acts as a translational inhibitor by targeting mRNA or by directing the chromatin site of a protein-binding partner. LincRNA-p21 is closely related to a variety of tumors and exerts its biological functions of carcinogenesis or tumor suppression through different pathways. In this paper, the research progress of the tumor-associated gene LincRNA-p21 was reviews
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Immunotherapy has become a new treatment for malignant tumors following surgery,radiotherapy,and chemotherapy.Tumor immunotherapy is a hot topic in basic medical research and clinical research,in which the study on checkpoint protein inhibitors has attracted more attention.The previous studies confirmed that blocking certain checkpoints,such as cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death protein-1 (PD-1),can exert immunomodulatory effects in solid tumor treatments.Immune checkpoint inhibitors have demonstrated good efficacy in recent years.The PD-1/programmed death ligand-1 (PD-L1) signaling pathway is one of the important pathways for tumor immune escape.PD-1/PD-L 1-targeted drugs can reactivate anti-tumor immunity and achieve good therapeutic effects in the treatment of various tumors.However,anti-PD-1/PD-L1 treatment has a certain adverse reaction rate,and the response rate of treatment needs to be improved.In this paper,the research progress of PD-1/PD-L1 signaling pathway and anti-PD-1/PD-L1 drugs in the treatment of solid tumors was summarized,such as malignant melanoma,lung cancer,renal cell carcinoma,gastrointestinal cancer,bladder cancer,etc.
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Objective To observe the different radiosensitivity induced by different doses of 137Csγ-ray irradiation between hematopoietic stem and progenitor cells. Methods Seventy-two C57BL/6 mice were randomly divided into control group and irradiated groups (2, 4 and 6 Csγ-ray irradiation, n=18 for each group). Mice of control group received sham irradiation, and the rest accepted 2, 4 and 6 Gy137Csγtotal body irradiation, respectively. After 14-day, 35-day and 56-day irradiation, the peripheral blood samples were collected by balls enucleation. The number of bone marrow nuclear cells, hematopoietic stem and progenitor cells were counted. Results The peripheral blood of irradiated mice showed significant changes in the number of white blood cells (WBC), red blood cells (RBC), platelets (PLT) and hemoglobin (HGB) in a dose-response relationship. Compared with the control group, the numbers of BMNCs and hematopoietic progenitor cells (HPCs) were significantly lower in irradiated group. At 35 d and 56 d after 6 Gy irradiation the numbers of BMNCs and HPCs were significantly lower than those of control group (P<0.05). There were no significant differences in numbers of BMNCs and HPCs between irradiated groups (2 and 4 Gy) and control group. The number of bone marrow hematopoietic stem cells (HSCs) was significantly lower in irradiated group than that in control group after 14-d and 56-d irradiation (P<0.05). Conclusion 137Csγ-ray irradiation has some damage in mouse hematopoietic system. The damage caused by radiation is persistent to hematopoietic stem cells.
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Objective To observe the injury effect of ionizing radiation on bone marrow derived c-kit+ cells.Methods Via-bility of c-kit+ cells was measured by bioluminescence;the level of c-kit+ cells reactive oxygen species was measured by DCFH-DA, the ability of colony-forming units was reflected by CFU-GM;proliferation and apoptosis of c-kit+ cells were measured by flow cy-tometry;the variation of pathway was detected by arrays of gene chip.Results Compared to control group(0 Gy).It had a decrease of c-kit+ cells′cell viability and the ability of colony-forming units after the cells receipt irradiation with the dose of 1 Gy and 4 Gy;and the level of cell reactive oxygen species,ratio of apoptosis cells increased.After 1 Gy irradiation exposure,the ratio of prolifera-tion(S/G2/M phase)cells increased compared to control group.However,when the c-kit+ cells were receipt 4 Gy irradiation expo-sure,the ratio of proliferation(S/G2/M phase)cells decreased.After 4 Gy irradiation exposure,the up-regulate genes contained Srxn1,Psmb5,Cdkn1a,Smc1b,Bcl2l1,Lrdd and so on;the down-regulate genes contained Mpo,Mtf1,Chek1,Rcc1 Ebag9,Ciapin1 and so on.Conclusion There was injury effect of ionizing radiation on c-kit+ cells,and it could induce variation of many pathways.
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Objective To observe the difference in number of epidermal stem cell and its function between wild-type (WT) mice and the third generation of Terc knockout (G3Terc-/-) mice. Methods Flowcytometry was used to analyse and sort epidermal stem cells;Quantitative real-time PCR is used to analyse the relative expression level of p 21 in epider-mal stem cells;Self-renewal ability was reflected by the number of colonies formed by epidermal stem cells. Results Basal and suprabasal ratios in epidermal stem cells in WT mice were (9.56 ± 1.06)% and (1.22 ± 0.08)% respectively; basal and suprabasal ratios in epidermal stem cell in G3Terc-/-mice were (17.36±3.56)%and (2.92±0.72)%respectively. Relative p21 expression level in G3Terc-/-mice was 6.40 fold to WT mice;Number of colonies formed by WT mice epidermal stem cells were (280.20±29.81) per 104 cell, number of colonies formed by G3Terc-/-mice epidermal stem cells were (29.28±5.24) per 104 cell, which present significant difference to each other(P<0.05). Conclusion Compared to WT mice, epidermal stem cells in G3Terc-/-mice were aging.
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Objective To investigate the protective effect of sesamol on radiation injury mouse bone marrow c-kit+cell,and further explore its possible mechanism.Methods Mouse bone marrow c-kit+cells were collected by immunomagnetic cell sorting method.There were 2 groups in the study:single dosing group and radiation plus drug group(doses of irradiation included 1 Gy and 4 Gy),and 10 -8 ~10 -3 mol/L sesamol were co-cultured with mouse bone marrow c-kit+cell half hour before irradiation exposure,cells were then cultured for 18 hours under the conventional culture conditions (37℃ and 5% CO2 ).The viability of mouse bone marrow c-kit+cells were measured by bioluminescence.The ability of colony-forming units were detected by CFU-GM and apoptotic rate of c-kit+cells were detected by Annexin V/PI antiapoptotic assay. Results Compared with control group,after 1 Gy and 4 Gy irradiated,cell viability of mouse bone marrow c-kit+cells were decreased 59.52% and 79.35%,respectively(P<0.05),the number of colony-forming were decreased 40.38% and 87.69%,respectively(P<0.05 ).Cell viability of c-kit+cells and the number of colonies formed were significantly increased with sesamol concentration between 10 -8 ~10 -6 mol/L,but not improve apoptosis rate.Conclusion Sesamol has protective effect on irradiation-induced injury in mouse bone marrow c-kit+cells,the mechanism of which may be related to the ability of hematopoietic progenitor cells proliferation.
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Objective To observe the effect of sesamol on the hematopoietic system in mice exposed to 4 Gy irradiation. Method Twenty C 57 BL/6 mice were randomly divided into control group, sesamol group, irradiated group and irradiated+sesamol group (n=5). Mice of control and sesamol group received sham irradiation, and the rest exposed to 4 Gy total body irradiation, dose rate 1.01 Gy/min. Mice in sesamol group and irradiated+sesamol group received a dose of 10 mg/kg sesamol administered by gavage every day for 7 days after irradiation exposure. Mice of other two groups were treated with vehicle solution. After 4 Gy irradiation 7 day, the peripheral bloods were collected. The levels of colony forming units-granulocyte-macrophage (CFU-GM) were detected. Results Compared to irradiation group, the level of WBC、cell count of BMNCs and CFU-GM significantly decreased in the irradiated mice, decreased in the irradiated mice (P<0.05). Compared to irradiation group, cell count of BMNCs and CFU-GM in the irradiated+sesamol group increased significantly (P<0.05). Conclusion Sesamol has a certain impact on the radiation-induced changes in hematopoietic system. The mechanism need to be further explored.
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<p><b>OBJECTIVE</b>To explore effects of iron overload on hematopoiesis in mice with bone marrow injury and its possible mechanism (s).</p><p><b>METHODS</b>C57BL/6 mice were divided into control, iron, irradiation, irradiation+iron groups. The iron-overloaded model of bone marrow injury was set up after mice were exposed to the dose of 4 Gy total body irradiation and (or) were injected iron dextran intraperitoneally. Iron overload was confirmed by observing iron deposits in mice and bone marrow labile iron pool. Additionally, the number of peripheral blood and bone marrow mononuclear cells and the frequency of erythroid cells and myeloid cells were counted and hematopoietic function was assessed.</p><p><b>RESULTS</b>(1)Iron overload occurred by bone marrow biopsy and flow cytometry analysis. (2)Compared with control group, the number of platelets [(801.9±81.2)×10⁹/L vs (926.0±28.2)×10⁹/L] and BMMNC and the frequency of erythroid cells and myeloid cells decreased. Moreover, hematopoietic colony forming units and single-cell cloning counts decreased significantly in irradiation group (P<0.05). (3)Compared with irradiation group, the number of platelets [(619.0±60.9)×10⁹/L vs (801.9±81.2)×10⁹/L] and the frequency of erythroid cells and myeloid cells decreased; moreover, hematopoietic colony forming units and single-cell cloning counts decreased significantly in irradiation+iron group (P<0.05). (4)Compared with irradiation group, ROS level increased by 1.94 fold in BMMNC, 1.93 fold in erythroid cells and 2.70 fold in myeloid cells, respectively (P<0.05).</p><p><b>CONCLUSION</b>The dose of 4 Gy total body irradiation caused bone marrow damage and iron overload based on this injury model, which could damage bone marrow hematopoietic function aggravatingly. And further study found that iron overload was closely related to increased ROS level in BMMNC. The findings would be helpful to further study the injury mechanism of iron overload on the hematopoiesis of bone marrow.</p>
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Animals , Mice , Bone Marrow , Wounds and Injuries , Bone Marrow Cells , Cell Biology , Hematopoiesis , Iron Overload , Mice, Inbred C57BLABSTRACT
Objective To observe the protective effect of N-acetyl-cysteine (NAC) on the injury of irradiation-in-duced bone marrow mononuclear cells (BMMNCs), and explore the possible mechanism. Methods There were 3 groups in the study:control group, irradiation group (doses of irradiation were 1 Gy and 4 Gy) and irradiation with NAC group (NAC was cocultured with BMMNCs half hour before irradiation). The 2×106/mL BMMNCs and the RPMI-1640 medium or 2×10-5 mol/L NAC were added into the 2 mL EP tubes according to the different requirement of groups. The tubes were then cul-tured in the 37℃CO2 incubator for 30 min and irradiated with 1 Gy and 4 Gy. The viability of BMMNCs was measured by bioluminescence. The level of reactive oxygen species (ROS) was measured by DCFH-DA, and the ability of colony-forming units was detected by CFU-GM. Results After 4 Gy irradiation exposure, the cell viability of BMMNCs was significantly lower in irradiation group (284 296.7±16 541.2) than that of control group (848 586.7±61 404.4). After 1 Gy irradiation expo-sure, the level of ROS was higher in irradiation group (6 750.0±103.5) than that of control group (5 710.7±56.2). The number of colony-forming units per 105 cells after irradiation exposure was (626.7±51.3), which was significantly lower than that of control group (986.7±100.7). Compared to irradiation group, the cell viability of BMMNCs increased to (352 770.0±23 466.1) in irradiation with NAC group. The level of ROS decreased to (5 430.0±61.0), and the number of colony-forming units per 105 cells increased to (773.3 ± 49.3). Conclusion NAC has protective effect on irradiation-induced injury in BMMNCs, which may be related with the decreased level of ROS. NAC can play the role of positive control for the following work.
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Objective To investigate the antitumor effect of 17aα-D-homo-ethynylestradiol-3-acetae on the mice transplanted with melanoma (B16) tumor cells,and to explore the possible synergistic effect with irradiation.Methods IRM-2 mice transplanted with B16 cells were randomly classified into control group,irradiation group,17aα-D-homo-ethynylestradiol-3-acetae drug ( high dose,medium dose,low dose) groups,and drug and irradiation combination group.Mice in drug group and the combination group were intraperitoneally injected with 5,7.5,and 10 mg/kg drug for 7 days.Mice in the irradiation and combination group received 1 Gy total body irradiation at 4 d after drug injection and then once a day for 5 days.The tumor inhibition efficiency,the number of bone marrow cells,thymus indices,and spleen indices were evaluated.Results Tumor weights in each drug group were significantly lower than those of the control( t =4.58,9.07,6.67,P ＜ 0.05 ).Drug combinated with 137Csγ-rays enhanced the antitumor effect so that the tumor weights in the combination group were significantly decreased ( t =8.06,10.35,6.71,P ＜0.05 ) in comparison with the control groups.Moreover,the numbers of marrow nucleated cells,thymus index and spleen index in the drug group were higher than those in the control group ( t =2.64,3.80,2.84,P ＜ 0.05 ).Conclusions 17aα-D-homo-ethynylestrudiol-3-acetae can inhibit cell growth of B16 melanoma in mice and may also have radioprotective effect on the hematopoietic system and immune system of mice.
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This study is to investigate the protective effects of the SB203580 against radiation induced mortality and intestinal injury of mice. A total of 67 male C57BL/6 mice (20.0-22.0 g) were matched according to body weight and randomly assigned to one of three groups: control, total body irradiation exposure (IR, 7.2 Gy) only, and IR (7.2 Gy) + SB203580 (15 mg x kg(-1)). 30 days survival rate was observed in the experiment. In intestinal injury experiment, the expression levels of caspase-3, Ki67, p53 and p-p38 were assayed in the mice intestine crypts. The results showed that the 30 days survival rate was 100% (control), 0 (IR) and 40% (IR+ SB203580), separately. Compared to the IR groups, the positive cells of caspase-3, p53 and p-p38 in crypt cells decreased 33.00%, 21.78% and 34.63%, respectively. The rate of positive cells of Ki67 increased 37.96%. Significant difference was found between all of them (P < 0.01). SB203580 potently protected against radiation-induced lethal and intestinal injury in mice, and it may be a potential radio protector.
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Objective: To investigate the reversal effects of pulsed magnetic fields(PMF) on the drug resistant cell line K562/ADR in vitro and their mechanism.Methods: MTT assay was used to determine the IC50 of ADR on K562/S and K562/ ADR cell lines,the detriment of PMF on the K562/ADR cell line and the reversal effects of the drug resistance after treatment with different frequencies of PMF.Flow cytometry(FCM) was applied to the assessment of concentration of intracellular ADR.Results: The drug-resistance multiple of the K562/ADR cell line was 29.36.PMF did not affect the growth of the K562/ADR cell line.Different frequencies of PMF produced different effects on the IC50 of the K562/ADR cell line.In the same condition,70Hz PMF produced the most significant effect and increasea the concentration of intracellular ADR.Conclusion: PMF can reverse the multidrug resistance of K562/ADR by enhancing the drug concentration in K562/ADR cells,and its frequency is correlated with its reversal effect:low fregucncy produces better effect.
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Lifelong blood cell production is achieved by the capacity of hematopoietic stem cell(HSC) to differentiate and self-renew.A growing body of evidence suggest that DNA damage induced HSC senescence may be the principal mechanism of aging and HSC exhaustion in response to the stress exposure.Understanding the mechanisms of HSC senescence will help to find new therapeutics that can ameliorate HSC injury induced by chemo-and radiotherapy,elucidate the molecular mechanisms whereby leukemia/cancer stem cell arise and evade cancer therapy by escaping senescence,and identify the novel molecular targets for intervention.