Synthesis and anti-radiation activity evaluation of substituted 2H-benzopyran-3-formylaniline compounds / 军事医学

Objective To discover new-structure active molecules in order to provide candidate compounds for anti-radiation drug research.Methods Conformational fixation and functional group conversion strategies were used to modify the structure of Ex-RAD before substituted 2H-benzopyran-3-formylaniline compounds were designed and synthesized.The anti-radiation activities of the synthesized compounds were screened via irradiated cell survival models and the cytotoxicity of the active compounds was examined.Western blotting assay was used to investigate the effects of the optimal compound on the expressions of apoptosis related proteins in irradiated cells.The anti-radiation activity of the optimal compound was evaluated through irradiated mice models.Results Twenty-one target compounds were synthesized,eight of which were found to significantly improve the survival of irradiated cells.Four compounds were selected for re-screening and cytotoxicity evaluation.Compound D19 was determined as the optimal compound that could affect the expressions of apoptosis related proteins in irradiated AHH-1 cells by Western blotting assay.Compared with the radiation group,the 30-day survival rate of D19 treated mice irradiated with 8.6 Gy of whole-body radiation increased by 70%.D19 showed protective effect on the blood system of non-lethal dose irradiated mice.Conclusion The novel compound D19 has shown strong anti-radiation activity and deserves more research.

STATUS OF THE CURRENT DOMESTIC REGULATORY BASE FOR ENSURING RADIATION SAFETY AND ANTI-RADIATION PROTECTION OF MILITARY PERSONNEL DURING THE PERIOD OF MARTIAL STATUS. / СТАН ЧИННОЇ ВІТЧИЗНЯНОЇ НОРМАТИВНОЇ БАЗИ ЩОДО ЗАБЕЗПЕЧЕННЯ РАДІАЦІЙНОЇ БЕЗПЕКИ ТА ПРОТИРАДІАЦІЙНОГО ЗАХИСТУ ВІЙСЬКОВОСЛУЖБОВЦІВ НА ПЕРІОД ВОЄННОГО СТАНУ.

Prerequisite. In the conditions of a full-scale invasion, the issue of radiation safety and anti-radiation protection in the Armed Forces of Ukraine (AFU) occupies a special place, since the aggressor country violated global geopolitical international decisions, occupied civilian nuclear facilities, in the process of their liberation servicemen mayhave to act in conditions of increased radiation risk, the possibility of using tactical nuclear weapons also is not excluded. OBJECTIVE: to investigate the state of the current national regulatory framework for ensuring radiation safety and anti-radiation protection of military personnel during the period of martial law. METHODS: bibliographic, analytical, historical, systematic approach. RESULTS: The main normative document on the organization of radiation safety and anti-radiation protection of both personnel and the population in Ukraine, as well as military personnel, currently in everyday conditions and in case of radiation accidents since 1998 and until now, are the State Hygienic Standards «Radiation Safety Standards of Ukraine (NRBU-97)¼. But neither in this document, nor in the transition to NRBU-2021-P, the issue of exposure to such a category as military personnel during the performance of combat (special) tasks is considered. The system of monitoring the radiation situation in Ukraine, documents on the organization of medical support for military personnel, including the Guidelines on the Medical Support of the Armed Forces of Ukraine for a Special Period (2019)and the Guidelines on the Organization of Radiation Safety in the Armed Forces of Ukraine (2020), were analyzed.modules of radiation safety principles in the Armed Forces of Ukraine were proposed. CONCLUSION: The unsolved problem of normalization of the radiation factor in the case of man-made and socio-political emergencies can create significant problems in the organization of anti-radiation protection of troops and the population in the case of the use of nuclear weapons or radiation accidents in a special period and requires anurgent solution. It is obvious that there is a need to develop regulatory documents regarding the response and planning of continuous activities to respond to potential nuclear and radiation threats during martial law, including relationships at all levels of the management vertical and methods of communication in the event of a threat.

Chemical constituents from the aerial parts of Orychophragmus violaceus.

A new alkaloid, demethylorychophragine A (1), together with 18 known compounds was isolated from the aerial parts of Orychophragmus violaceus. Structure of the new compound was identified by extensive spectroscopic techniques. 2 and 3 were isolated from nature for the first time. Known compounds were identified by comparison with data reported in the literature. All compounds were evaluated for anti-radiation activities against X-ray irradiation in HUVEC cell line. Results showed that 10, 12, and 15 showed excellent anti-radiation activity. All compounds were tested for cytotoxic activity against SH-SY5Y and HeLa cell lines. 16 exhibited significant cytotoxicity activity against SH-SY5Y cells, with IC50 value of 23.86 ± 0.38 µM (p = 0.045). The anti-inflammatory effects of all compounds were assessed by determining their ability to inhibit the production of NO, which was induced by stimulating the RAW264.7 murine macrophage cell line with lipopolysaccharide. 16 markedly decreased NO to a level of 27.34 ± 1.29 µM.

Review of the Efficacy and Mechanisms of Traditional Chinese Medicines as a Therapeutic Option for Ionizing Radiation Induced Damage.

Ionizing radiation damage refers to acute, delayed, or chronic tissue damage associated with ionizing radiation. Specific or effective therapeutic options for systemic injuries induced by ionizing radiation have not been developed. Studies have shown that Chinese herbal Medicine or Chinese Herbal Prescription exhibit preventive properties against radiation damage. These medicines inhibit tissue injuries and promote repair with very minimal side effects. This study reviews traditional Chinese herbal medicines and prescriptions with radiation protective effects as well as their mechanisms of action. The information obtained will guide the development of alternative radioprotectants.

Radioprotective effects and mechanisms of animal, plant and microbial polysaccharides.

Ionizing radiation is increasingly used to successfully diagnose many human health problems, but ionizing radiation may cause damage to organs/tissues in the living organisms such as the spleen, liver, skin, and brain. Many radiation protective agents have been discovered, with the deepening of radiation research. Unfortunately, these protective agents have many side effects, which cause drug resistance, nausea, vomiting, osteoporosis, etc. The polysaccharides extracted from natural sources are widely available and low in toxicity. In vivo and in vitro experiments have demonstrated that polysaccharides have anti-radiation activity through anti-oxidation, immune regulation, protection of hematopoietic system and protection against DNA damage. Recently, some studies have shown that polysaccharides were resistant to radiation. In the review, the anti-radiation activities of polysaccharides from different sources are summarized, and the anti-radiation mechanisms are discussed as well. It can be used to develop more effective anti-radiation management drugs.

Structure, Molecular Modification, and Anti-radiation Activity of Melanin from Lachnum YM156 on Ultraviolet B-Induced Injury in Mice.

The purpose of this study was to examine the protective effects of intracellular homogeneous melanin produced by Lachnum YM156 (LIM) against ultraviolet B (UVB) induced damage in mice. The possible structural formula of the LIM was concluded based on elemental analysis, ultraviolet-visible spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and mass spectrometry (MS). The LIM was modified by arginine to improve its water solubility and biological activities. LIM and ALIM show significant anti-radiation activity in which LIM and ALIM protect the skin under UV radiation. Results indicate that activities of anti-oxidant enzymes in skin were improved after treatment of LIM or ALIM. In addition, LIM and ALIM inhibited over expression of the pro-inflammatory cytokines, including interleukin (IL)-1α, IL-1ß, and IL-6 and tumor necrosis factor-α (TNF-α). The protection ability of ALIM was higher than that of LIM at the same dose. Thus, applied LIM and ALIM may be a promising radiation-protective agent.

Radioprotective effect of epimedium on neurogenesis and cognition after acute radiation exposure.

The radioprotective effect of herb epimedium (or yin yang huo) extract (5 g/kg, oral administration daily for 4 weeks) on neurogenesis and cognition after acute radiation exposure with 5.5 Gy was evaluated in Balb/c mice by behavioral tests and immunohistochemical study. The results indicated that epimedium extract could improve animal weight loss, locomotor activity and spatial learning and memory which are similar to pre-irradiation intraperitoneal injection (100 mg/kg) of amifostine phosphate, a well- known radioprotective drug. Immunohistochemical study showed that epimedium extract prevented the loss of proliferation cells, newly generated neurons, and interneurons in the hilus, in particular, the subgranular zone of the dentate gyrus. It suggests that herb epimedium may be a promising radio-neuro-protective drug to prevent radiation-induced neuropsychological disorders.

Chemical constituents from the fruits of Psoralea corylifolia and their protective effects on ionising radiation injury.

Two new flavonoids, corylifol F (1) and corylifol G (2), together with 19 known compounds, were isolated from the fruits of Psoralea corylifolia L.. The structures of these compounds were determined by interpretation of spectroscopic data and comparison with literature properties. The radioprotective effects of the isolated compounds against ionising radiation damage were also evaluated in vitro. The results showed that corylifol A exhibited radioprotective effects in both HBL-100 and MCF-7 cells, while psoralen, isopsoralen, corylifol C and bakuchiol showed obvious selective action to protect HBL-100 cells against damage caused by ionising radiation.

Study on anti-radiation effect of Citrus aurantium L. polysaccharides-B / 中国药理学通报

Aim To investigate the protective effect of Citrus aurantium L. polysaccharides-B(CALB) on ra-diation induced by 60Co γ-ray in mice. Methods The BALB/c mice were randomly divided into blank control group, radiation model group, CALB administration group (high, medium and low dose), and positive control group(black fungus polysaccharide,HP). The mice were administered orally for 30 days. After the last administration for three hours,the survival rates on the 2nd day and the 14th day of the blank control group and the irradiated mice after the single radioac-tive irradiation (7 Gy) with 60Co γ-ray were meas-ured. In addition, DNA content and micronucleus of bone marrow cells, SOD, GSH-Px activities, MDA content in serum, liver and brain tissues in mice, TChE activity in brain tissues and spleen and thymus index of mice were detected after one-time whole body irradiation with 60Co γ-ray (3 Gy). Results Each dose group of CALB could significantly improve the survival rate of irradiated mice,increase the DNA con-tent of mouse bone marrow cells and reduce the number of micronuclei in bone marrow cells. In addition, CALB could also increase the thymus and spleen index and the levels of SOD and GSH-Px in serum,brain and liver tissues of mice,and reduce the content of MDA. Conclusion CALB has protective effect on radiation injury,which can be used for further development and utilization of Fructus aurantii.

Design of a garbage bin suitable for application of nuclear medicinal waste product to defend radiation / 中国中西医结合急救杂志

A garbage bin was developed specifically to defense radiation of nuclear medicinal waste product;by the bin the waste material can be collected and stored during the processes when medical personnel managing radionuclide, such as opening bottles, diluting, dividing, labeling, washing, injecting and administrating the medicine, under these circumstances, the exposure and damage caused by the nuclear radiation to the personnel and their surrounding people can be effectively decreased or avoided compared to those the medical workers taking the nuclear waste material to throw into an ordinary garbage bin.

Design,synthesis and preliminary anti-radiation activityof novel LPA2 receptor agonists / 国际药学研究杂志

Objective To design and synthesize novel G protein-coupled lysophosphatidic acid 2(LPA2)receptor agonists with anti-radiation activity. Methods Nine new LPA2 receptor agonists(Ⅰ2-Ⅰ5 andⅡ1-Ⅱ5)were designed and synthesized using DBIBB as the lead compound. The anti-radiation activity was assayed by the MTS method using the human umbilical vein endothelial cells(HUVEC)irradiated with 8.0 Gy 60Coγray. Results and Conclusion Nine target compounds notreported in the literature were synthesized and their structures were confirmed by 1H NMR and MS. The results showed thatⅠ4 andⅡ1 have obvious anti-radiation ac-tivity,indicating that this kind of compounds is worth further studying.

Synthesis and anti-radiation activity of coumarinbenzyl (sulfoxide) sulfone derivatives / 国际药学研究杂志

Objective Using Ex-Rad as lead compound to design and synthesize coumarin benzyl(sulfoxide)sulfone derivatives with anti-radiation activity. Methods The target compounds were synthesized from methyl 2-mercaptoacetate and 4-bromomethylbenzoic acid through three steps. The anti-radiation activity was assayed by the MTT method using the HUVEC cells irradiated with 8Gy 60Co γ ray. Results Sixteen compounds containing a coumarin benzyl sulfoxide or sulfone group were synthesized and the structures were confirmed by 1H NMR and HRMS. Preliminary evaluation of the 16 compounds demonstrated that 6a, 6b, 6c and 6d exhibited potent anti-radiation activities. Conclusion The anti-radiation activities of 6a, 6b, 6c and 6d were significant, indicating that this kind of compounds is worth further study.

Extraction, purification and anti-radiation activity of persimmon tannin from Diospyros kaki L.f.

In this study, persimmon tannin was extracted from Diospyros kaki L.f. using ultrasound-assisted extraction and purified by D101 macroporous resin column chromatography and polysulfone ultrafiltration membrane. The tannin content of the final persimmon tannin extracts was attained to 39.56% calculated as catechin equivalents. Also, the radioprotective effects of persimmon tannin for HEK 293T cells proliferation and apoptosis after Gamma irradiation were investigated by CCK-8, Hoechst 33258 staining, flow cytometry assay and intracellular reactive oxygen species assay (ROS). Persimmon tannin was pre-incubated with HEK 293T cells for 12 h prior to Gamma irradiation. It was found that pretreatment with persimmon tannin increased cell viability and inhibited generation of Gamma-radiation induced ROS in HEK 293T cells exposed to 8 Gy Gamma-radiation. The percentage of apoptotic cells were only 6.7% when the radiation dose was 8 Gy and pretreated with 200 µg/ml of persimmon tannin. All these results indicated that persimmon tannin offered a potent radioprotective effect on cell vitality and cell apoptosis of Gamma-radiation exposure in HEK 293T cells. This study would serve as a pre-clinical evaluation of persimmon tannin for use in people with radiation protection.

Anti-radiation drugs for radiotherapy:research advances / 国际药学研究杂志

Anti-radiation drugs can prevent humans from radiation injury,reduce the clinical symptoms of radiation sickness and promote early recovery. With the wide application of radiotherapy in the treatment of malignant tumor patients ,anti-radiation drugs for radiotherapy have become more and more important. Tradiational anti-radiation drugs include free radical scavengers,super?oxide dismutase(SOD)and SOD mimetics,nitroxides,natural antioxidants and cytokines. These drugs have the common disadvantag?es of serious side effects,narrow therapeutic time window,poor stability and high cost. Therefore,it is particularly important and ur?gent to discover anti-radiation drugs which are highly efficient,lowly toxic,inexpensive and easy to use. In recent years,with the deepening understanding of cell signaling pathways,angiotensin converting enzyme inhibitors(ACEI)and apoptosis regulators have gradually become a hot spot for anti-radiation drugs research. This review summarizes the advantages and disadvantages as well as the future trends of anti-radiation drugs with proven or potential usefulness in radiotherapy.

Anti-radiation drugs for radiotherapy: Research advances / 国际药学研究杂志

Anti-radiation drugs can prevent humans from radiation injury, reduce the clinical symptoms of radiation sickness and promote early recovery. With the wide application of radiotherapy in the treatment of malignant tumor patients, anti-radiation drugs for radiotherapy have become more and more important. Tradiational anti-radiation drugs include free radical scavengers, superoxide dismutase(SOD) and SOD mimetics, nitroxides, natural antioxidants and cytokines. These drugs have the common disadvantages of serious side effects, narrow therapeutic time window, poor stability and high cost. Therefore, it is particularly important and urgent to discover anti-radiation drugs which are highly efficient, lowly toxic, inexpensive and easy to use. In recent years, with the deepening understanding of cell signaling pathways, angiotensin converting enzyme inhibitors (ACEI) and apoptosis regulators have gradually become a hot spot for anti-radiation drugs research. This review summarizes the advantages and disadvantages as well as the future trends of anti-radiation drugs with proven or potential usefulness in radiotherapy.

Anti-radiation traditional Chinese medicine and natural products:research advances / 国际药学研究杂志

With the progress of science and technology, the development of nuclear industry and the extensive use of cancer radiotherapy, people are exposed on ionizing radiation more frequently than before. Therefore, the research on anti-radiation drugs has become the hotspot in pharmaceutical industry. However, the synthetic anti-radiation drugs have several side effects, more and more investigators have focused on the traditional Chinese medicine (TCM) and natural products. This review reports the research advances in anti-radiation TCM and natureal products.

Anti-radiation traditional chinese medicine and natural products: Research advances / 国际药学研究杂志

With the progress of science and technology- the development of nuclear industry and the extensive use of cancer adiotherapy - people are exposed on ionizing radiation more frequently than before. Therefore- the research on anti-radiation drugs ias become the hotspot in pharmaceutical industry. However- the synthetic anti-radiation drugs have several side effects- more and nore investigators have focused on the traditional Chinese medicine (TOM) and natural products. This review reports the research idvances in anti-radiation TCM and natureal products.

Purification, structure and anti-radiation activity of melanin from Lachnum YM404.

Extracellular melanins (LEM404) were extracted from Lachnum YM404 with a yield of 3.45 g/L. LEM404-a, LEM404-b, LEM404-c, LEM404-d and LEM404-e were fractionated from LEM404 by Sephadex G-15 column. LE404-a was detected as the homogeneous component with molecular weight of about 432.18 Da. Based on the elemental analysis, mass spectrometry, infrared spectroscopy, pyrolysis-GC-MS and NMR analysis, the molecular formula (C22H12N2O4S2) and structural formula of LEM404-a were concluded. LEM404-a could significantly increase the survival rates of Escherichia coli, Staphylococcus aureus and Saccharomyces cerevisiae under UV radiation. Anti-radiation experiments in mice showed that the skin manifestations in mice of low radiation dose experimental group (LEG) were similar to those in blank control group (BCG). Compared with the control groups (LCG and HCG), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in mice of experiment groups (LEG and HEG) were improved significantly while malondialdehyde (MDA) content were decreased significantly, indicating that LEM404-a had strong anti-ultraviolet radiation activity.

The mechanisms of ARPD in treating radiation-induced lung fibrosis in rats / 中华放射医学与防护杂志

Objective To investigate the therapeutic effects and mechanism of anti-radiation pneumonia decoction(ARPD) on radiation induced lung fibrosis in rats.Methods One hundred and five male SD rats in a SPF grade were divided into Chinese medicine group,single radiation group and control group by random digits table method,with 35 in each group.After anesthetization,rats in Chinese medicine and single radiation groups were exposed to 6 MV X-rays at the dose of 15Gy.Rats in Chinese medicine group were treated with ARPD at the dosage of 10 ml·kg-1 ·d-1 once a day,but rats in single radiation group did not receive ARPD treatment.Rats in control group were treated with neither irradiation nor drugs.Five rats of each group were killed and the lung tissues and blood samples were collected at 15,30,60,75,90,105 and 140 d.The pathological changes of lung tissues were observed and the tissue protein and gene expressions of TGF-β1,PAI-1 and collagen type Ⅲ(C Ⅲ) were assayed by Western blot and RT-PCR.ELISA was used to detect serum TGF-β1 and plasma PAI-1.Tissue and serum HYP were determined by acid hydrolysis and alkaline hydrolysis methods respectively.Results Inflammation was found in the lung tissues of all the exposed rats.Obvious pathological lung fibrosis was found at 60 d,the inflammation and the fibrosis in treated group were slighter than those in single radiation group.In Chinese medicine group,the protein and gene expression levels of TGF-β1,PAI-1,C Ⅲ 30 d(Protein:t =2.49-3.74,t =2.63-4.57 and t =2.76-3.83;Gene:t =2.59-4.33,t =2.83-4.62 and t =2.83-3.96,P＜0.05),serum TGF-β1 and plasma PAI-1 15 dlater (t =2.85-6.27 and t =3.69-5.27,P＜0.05),and the levels of tissue and serum HYP60 dlater (t=3.65-4.40 and t =6.56-3.75,P＜0.05),all of them were lower than those in single radiation groups.There were significant positive correlations between tissue TGF-β1 and PAI-1 as well as C Ⅲ (Protein expression:r =0.604,0.759,P ＜0.05;Gene expression:r=0.519,0.816,P＜0.05).Conclusions ARPD may inhibit the pulmonary fibrosis by decreasing the levels of TGF-β1,PAI-1 and C Ⅲ.

Advance in research on anti-radiation active substances from plankton in the Antarctic / 中国海洋药物

'Ozone hole' , which cause a great increment of the UV radiation to the earth surface, is a exclusive phenomena over the Antarctic. After living in high UV radiation for a long time , plankton in the Antarctic have produced many anti-radiation active substances. In this article, the properties, configurations, functions, etc. of anti-radiation active substances in algae, bacteria and fungi in the Antarctic wen: summarized. At the same time, significative illuminations on the studies and utilization of anti-radiation and anti-tumour active substances are expected.