Establishment of NaLuF_(4):15%Tb-based low dose X-PDT agent and its application on efficient antitumor therapy

X-ray excited photodynamic therapy(X-PDT)is the bravo answer of photodynamic therapy(PDT)for deep-seated tumors,as it employs X-ray as the irradiation source to overcome the limitation of light penetration depth.However,high X-ray irradiation dose caused organ lesions and side effects became the major barrier to X-PDT application.To address this issue,this work employed a classic-al co-precipitation reaction to synthesize NaLuF_(4):15%Tb^(3+)(NLF)with an average particle size of(23.48±0.91)nm,which was then coupled with the photosensitizer merocyanine 540(MC540)to form the X-PDT system NLF-MC540 with high production of singlet oxygen.The system could induce antitumor efficacy to about 24%in relative low dose X-ray irradiation range(0.1-0.3 Gy).In vivo,when NLF-MC540 irradiated by 0.1 Gy X-ray,the tumor inhibition percentage reached 89.5%±5.7%.The therapeutic mechanism of low dose X-PDT was found.A significant increase of neutrophils in serum was found on the third day after X-PDT.By immunohistochemical staining of tumor sections,the Ly6G^(+),CD8^(+),and CD11c^(+)cells infiltrated in the tumor microenvironment were studied.Utilizing the bilat-eral tumor model,the NLF-MC540 with 0.1 Gy X-ray irradiation could inhibit both the primary tumor and the distant tumor growth.De-tected by enzyme linked immunosorbent assay(ELISA),two cytokines IFN-γand TNF-αin serum were upregulated 7 and 6 times than negative control,respectively.Detected by enzyme linked immune spot assay(ELISPOT),the number of immune cells attributable to the IFN-γand TNF-αlevels in the group of low dose X-PDT were 14 and 6 times greater than that in the negative control group,respectively.Thus,it conclude that low dose X-PDT system could successfully upregulate the levels of immune cells,stimulate the secretion of cy-tokines(especially IFN-γand TNF-α),activate antitumor immunity,and finally inhibit colon tumor growth.

Effects of low dose pre-irradiation on the toxicity of cyclophosphamide

Objective:The aim of the study was to investigate the effects as well as the possible mechanisms of low dose γ-ray pre-irradiation on hepatic damage,DNA damage of peripheral lymphocytes and genetic material damage caused by high dosage of cyclophosphamide(CTX).Methods:Kunming strain male mice were randomly divided into five groups:control group,sham-irradiated group,low dose irradiation group(LDR group),cyclophosphamide chemotherapy group(CTX group) and low dose irradiation combined with chemotherapy group(LDR + CTX group).Having being raised for one week,all the mice were implanted subcutaneously with S180 cells in the left inguen(control group excluded).On days 8 and 11,mice of LDR and LDR + CTX groups were given 75 mGy whole-body γ-irradiation,30 h later mice of CTX and LDR + CTX groups were injected i.p.3.0 mg cyclophosphamide.All the mice were sacrificed on day 13.DNA damage of the peripheral lymphocytes was analyzed using single cell gel electrophoresis(SCGE);ALT activity,total protein(TP) and albumin(ALB) of the plasma were analyzed using automatic biochemistry analyzer;MDA content,SOD and GSH-PX activity of the hepatic homogenate were analyzed using chromometry;genetic material damage was analyzed using micronucleus frequency(MNF) of polychromatoerythrocytes(PCE) in bone marrow.Results:1.Differences of MDA contents,SOD and GSH-PX activity of hepatic homogenate between 5 groups had notable statistical significance(P < 0.01);in control group MDA content was the lowest,SOD and GSH-PX activity were the highest,while in CTX group MDA content was the highest,SOD and GSH-PX activity were the lowest;compared with CTX group MDA content decreased significantly(P < 0.01) and SOD and GSH-PX activity increased significantly(P < 0.05) in LDR + CTX group.2.Differences of ALT activity of plasma between 5 groups had no statistical significance(F = 1.262,P > 0.05).Differences of TP and ALB of plasma between 5 groups had statistical significance(F = 12.879 and 6.336 respectively,P < 0.01);TP and ALB in control group were higher than those of other groups and compared with sham-irradiated group,TP and ALB in LDR group elevated significantly(P < 0.05).3.Differences of DNA damage of peripheral lymphocytes had notable statistical significance(F = 6.383,P < 0.01);DNA damage in control group was the lightest,while DNA damage in CTX group was the severest;compared with CTX group,DNA damage in LDR + CTX group was much lighter(P < 0.05).4.MNF of PCE between 5 groups had remarkable significance(F = 179.652,P < 0.01);compared with control group and sham-irradiated group,MNF in CTX group increased significantly(P < 0.01);compared with CTX group,MNF in LDR + CTX group had a tendency of decline,which had no statistical significance(P > 0.05).Conclusion:1.CTX can damage the hepatic tissue through oxidative stress;75 mGy γ-irradiation before CTX chemotherapy can induce activities of anti-oxidative enzymes,promote elimination of free radicals,so as to alleviate the damaging effects of oxidative stress to hepatic tissue caused by high-dose chemotherapy.2.A 75 mGy γ-irradiation before CTX chemotherapy has no obvious effect on ALT activity of plasma,but may have protective effect on the protein synthesis function of liver.3.High-dose CTX chemotherapy can cause DNA damage of peripheral lymphocytes;75 mGy γ-irradiation before chemotherapy may have certain protective effect on DNA damage.4.CTX has potent mutagenic effect,can cause significant increase of MNF of PCE;75 mGy γ-ray pre-irradiation did not show obvious protection against genetic toxicity of high-dose CTX chemotherapy.

Study on the Antitumor Effects of Low-energy Laser Irradiation Combined with Cyclophosphamide

Systematic experiments about the antitumor effects of low energy laser irradiation combined with the traditional antitumor medicine of cyclophosphamide were conducted using the experimental model of mouse S180 ascites sarcoma.The three groups of tumor bearing mice were irradiated upon the inner corners with the dosages of 11 00,14 67 and 22 00 J·cm -2 LELI respectively,and injected with CYT intraperitoneally to observe the changes of the survival time,the ascites growth speed,and the kinetic changes of immune functions.The survival times of the three groups of CYT/LELI combination were obviously longer than those of the tumor and CYT control groups.Correspondingly,the amounts of ascites,tumor cells densities and total tumor cells in CYT/LELI groups decreased significantly,while the death ratio of the tumor cells increased.Comparatively,the group of 22 00 J·cm -2 LELI combined with CYT showed the most ideal antitumor effects,and the life prolongation ratio was up to 53 20%.

Meso-scale Discovery Assay Detects the Changes of Plasma Cytokine Levels in Mice after Low or High LET Ionizing Irradiation

Objective To obtain precise data on the changes in the levels of 29 cytokines in mice after high or low linear energy transfer(LET)irradiation and to develop an accurate model of radiation exposure based on the cytokine levels after irradiation.Methods Plasma samples harvested from mice at different time points after carbon-ion or X-ray irradiation were analyzed using meso-scale discovery(MSD),a high-throughput and sensitive electrochemiluminescence measurement technique.Dose estimation equations were set up using multiple linear regression analysis.Results The relative levels of IL-6 at 1 h,IL-5 and IL-6 at 24 h,and IL-5,IL-6 and IL-15 at 7 d after irradiation with two intensities increased dose-dependently.The minimum measured levels of IL-5,IL-6 and IL-15 were up to 4.0076 pg/mL,16.4538 pg/mL and 0.4150 pg/mL,respectively.In addition,dose estimation models were established and verified.Conclusions The MSD assay can provide more accurate data regarding the changes in the levels of the cytokines IL-5,IL-6 and IL-15.These cytokines could meet the essential criteria for radiosensitive biomarkers and can be used as radiation indicators.Our prediction models can conveniently and accurately estimate the exposure dose in irradiated organism.

Effect of Low Energy Far-Infrared Irradiation on Facial Skin for Healthy People

Objective: Utilizing VISIA skin tester to quantitatively evaluate the effect of low energy far-infrared irradiation on healthy people’s facial skin. Methods: 60 volunteers were selected in hospital from September 2019 to June 2020, and the total score of face, skin spots, texture, wrinkles and pores were observed before and after low energy far-infrared irradiation treatment with VISIA skin tester. Results: After 2 weeks of low energy far-infrared irradiation treatment, the total skin score of volunteers increased significantly (P < 0.01). In the itemized statistics, the moisture value, stain value and wrinkle value increased significantly (P < 0.05). Conclusion: Low energy far-infrared irradiation can significantly improve the facial skin quality of healthy people.

Polarization visualization for low-irradiance regions by perceptually uniform color space

Currently,polarization visualization strategies are accomplished by mapping polarization information into a perceptually uniform color appearance model CAM02-UCS.However,the deviation of the CAM02-UCS space from the lightness prediction results in an inaccurate match between the polarization information and the perceptual information.In this paper,we propose a novel polarization visualization strategy based on the perceptual uniform space Jzazbz.The polarization visualization be completed by placing the polarization information into the lightness Jz,colorfulness Cz and hue angle hz channels of the Jzazbz space.The experimental results show that the proposed method can significantly improve the lightness of the low irradiance and high polarization region,hence more polarization information can be sensed by human visual system.

Environmentally Induced Under-Development of Seeds in Garden Pea and Its Underlying Factors

Under-development of pea (Pisum sativum L.) seeds in normally developed pods, resulting in “unfilled pods”, has been a serious problem in the greenhouse cultivation in Wakayama Prefecture, one of the major regions of pea cultivation in Japan. This phenomenon appears to be induced by low temperature and low solar irradiation during pea growing season. This study examined the relationship between this seed under-development and sucrose-to-starch metabolism in developing seeds and pods after flowering. The starch content, ADP-glucose pyrophosphorylase (AGPase) and sucrose synthase activities of a pea cultivar, Kishuusui, were monitored through seed development in shading-treatment plot and in control plot. Results showed that the present treatment induced the depression of starch accumulation and AGPase activity in developing seeds compared with control, which might cause the occurrence of under-development of seeds and unfilled pods. Surplus carbohydrates from source organs might be stored in pod walls, as expected from higher starch level and AGPase activity in treated pod walls. The necessity of thermostable AGPase variants in pea to prevent the unfilled-pod problem was discussed.

CURRENT STUDIES ON BIOLOGICAL EFFECTS OF LOW LEVEL INTERNAL IRRADIATION

The biological effects of relative low level internal irradiation were introduced. 1. Life span studies on carcinogenesis. Pacific Northwest Laboratory observed 3782 rats given a single inhalation of 239Pu O2 at initial lung burden ranging from 0.25 to 180 nCi. Significant life span shortening was found at lung dose > 8 Gy and it was indicated that the presence of a 'possible' threshold of about 1 Gy for lung tumor formation. 2. Health effects of radon and its progeny. Both experimental and epidemiological survey were studied. The nominal probability coefficient (fatality) for the public and workers are 7.90×105 per mJhm-3 (2.77 ×10~4 per working level month, WLM). 3. Health effects of 3H on postnatal brain development and neurobehavior, genetic effects, carcinogenic effects and adaptive effects of 3H were investigated. 4. Study on the effects of neuroendocrine system under low level irradiation of 75Se (Auger electron emitter) and 35S (β-particles emitter). The results showed that the neuroendocrine system is very sensitive to small dose of internal irradiation.