Dose-Response最新文献

Background: We are exposed to natural ionizing radiation and other genomic stressors throughout life and radiophobia has caused much harm to society. The main basis for radiophobia is the invalid linear no-threshold (LNT) hypothesis for cancer induction, which the System of Radiological Protection (SRP) is linked to. Largely unknown to the public, evolution-associated genomic stress adaptation (gensadaptation) over many previous generations now provides protection to all lifeforms from low radiation doses. Objective: To help bring about an improved SRP not linked to the invalid LNT hypothesis for radiation-caused health detriment and to promote low-dose radiation therapy for different diseases. Methods: All-solid-cancer mortality risk dose-response relationships for A-bomb survivors were generated based on published LNT-modeling-related results. Dose-response relationships for lung cancer prevention by low-dose radiation were generated by linear interpolation based on published data from a study using > 15,000 mice. Uncertainty characterization was based on Monte Carlo calculations for binomial and Poisson distributions. New dose characterization tools were used for threshold dose-response relationships for radiation-caused cancer mortality. Results: The all-solid-cancer mortality risk for A-bomb survivors transitioned from LNT to threshold-linear when adjusted for key missing uncertainty at low doses. The prevention of lung cancer in mice by low radiation doses depends on the radiation absorbed dose and type. Conclusions: The SRP should be linked to population dose thresholds rather than the invalid LNT hypothesis and small likely harmless radiation doses could possibly be used in treating different diseases.

Background: Abrupt inflammation and alveolar epithelial membrane damage, which may cause the alveolar membrane's malfunction, are related to acute lung injury (ALI). This could eventually lead to pulmonary fibrosis. While lung injury can happen in many ways, the current study will concentrate on the changes in lung pathology mediated by paraquat (PQ). Paraquat, a widely used herbicide, targets lung toxicity through inflammation and oxidative stress, which significantly contribute to lung damage.

Objective: The current research was to ascertain whether low-dose gamma radiation (R) and misoprostol (MP) could lessen the lung inflammatory cascade started by PQ injection in rats.

Methods: The ALI model was induced by I.P. injection of PQ (20 mg/kg once), and then treatment was done by MP and/or R for 14 days, and finally, the biochemical and histological parameters were measured in the lung tissues.

Results: Our data suggest that PQ can promote ALI through TGF-β/smad, Notch, NF-κB, and ET-1 signaling pathways, resulting in EMT. These suggestions were supported by increased levels of TGF-β, inflammatory cytokines, α-SMA, NF-κB, ET-1, CTGF protein, and LPA, whereas PPAR-γ decreased. The aforementioned results have been confirmed by lung histopathology.

Conclusion: We suggest that the pulmonary inflammatory cascade was hindered and all the previously described gauges improved with R and/or MP therapy.

Purpose: The aim is to investigate the response of peripheral blood lymphocytes to a low-dose neutron-gamma field. Methods: The human peripheral blood was exposed to low-dose neutron-gamma radiation ex vivo. Flow cytometry was utilized to evaluate the changes in cell cycle and protein levels of p21, CDK2, and γH2AX. qPCR analysis was conducted to investigate the mRNA transcription of p21 and CDK2. The chromosomes aberration and micronucleus rate in peripheral blood lymphocytes were observed by microscope. Results: Within the radiation dose range of 0-5976 μGy, compared to the "0" dose group, there was an increase in the proportion of cells in G1 phase and a decrease in the proportion of cells in G2 phase. Additionally, there was an upregulation of p21 and γH2AX protein expression, a downregulation of CDK2 protein expression, and an increase in transcription levels of p21 and CDK2 mRNA. Furthermore, there was an elevation in the rate of chromosome aberrations in peripheral blood lymphocytes; however, no significant change of micronuclei rate was observed. Conclusions: The response of human lymphocytes to low dose neutron gamma irradiation can be reflected by the changes of cell cycle, chromosome aberration and RPS18 expression.

Objectives: Melatonin has been documented as an antioxidant agent. Numerous investigations have documented melatonin's radioprotective impact; however, investigation of its role post-irradiation requires further studies. Thus, the present study investigated melatonin's mitigating effect against radiation-induced alteration in the ovaries and reproductive hormones in female albino rats. Methods: Melatonin (10 mg/kg body weight, i. p.) was administered to the animals for 7, 11, and 15 days after whole-body exposure to 4 Gy γ-radiation. Results: The results demonstrated that melatonin has significantly attenuated the radiation-induced oxidative stress in the ovary, manifested by a decrease in protein carbonyl and malondialdehyde in conjunction with an increase in total antioxidant capacity. In addition, melatonin has alleviated the radiation-induced increase of the pro-inflammatory cytokines (tumor necrotic factor alpha, interleukin-6, interleukin-1 beta) and caspase-3 levels in the serum. These results were accompanied by a noticeable improvement in serum E2-estradiol, testosterone, progesterone, follicle-stimulating hormone, and luteinizing hormone compared to their respective levels in the irradiated group. Conclusion: It could be concluded that melatonin is an effective agent for minimizing the deleterious impacts of radiation on the ovaries and reproductive hormones through synergistic interdependence between anti-inflammatory, antioxidant, and anti-apoptotic activities.

The combination of thoracic radiotherapy and immune checkpoint inhibitors (ICIs) had demonstrated a synergistic therapeutic effect, albeit with the occurrence of overlapping pulmonary toxicities. We established a mouse model using programmed cell death protein-1 (PD-1) antibody at different time points after thoracic radiotherapy. Hematoxylin and eosin (HE) staining, as well as TUNEL staining, were utilized for the morphological assessment of lung tissue damage. Inflammatory cells and cytokines present in bronchoalveolar lavage fluid (BALF) were analyzed using flow cytometry and cytometric bead array immunoassay (CBA). Additionally, immunohistochemistry (IHC) and immunofluorescence (IF) staining were conducted to observe the infiltration of inflammatory cells in lung tissue. Immediate administration of PD-1 antibody after thoracic radiotherapy resulted in more severe lung tissue injury compared to delayed administration. Concurrent treatment led to an increase in lymphocytes and neutrophils in BALF, as well as higher levels of inflammatory cytokines. IHC and IF analysis revealed that neutrophils, macrophages, and lymphocytes were more prominent in the concurrent treatment group. A more severe lung injury occurred when PD-1 antibody was given simultaneously with thoracic radiotherapy, possibly due to increased inflammation caused by the combination treatment.

Objectives: Cytokinins are plant hormones that regulate cell growth and differentiation. In particular, zeatin (ZTN) delays cellular senescence of human fibroblasts and keratinocytes and exhibits anticancer activity. Chemotherapy-induced anemia is a major side effect of anticancer therapy secondary to premature senescence of red blood cells (RBCs). Herein, we investigated the biochemical and molecular mechanisms underlying ZTN action in human RBCs. Methods: Colorimetric assays were used to quantify hemolysis and related markers and flow cytometric analysis was applied to examine eryptosis through phosphatidylserine (PS) exposure by annexin-V-FITC, intracellular Ca²⁺ by Fluo4/AM, reactive oxygen species (ROS) by H₂DCFDA, and cell size from forward scatter (FSC). Results: ZTN at 200 μM induced significant hemolysis and K⁺, Na⁺, AST, and LDH leakage. ZTN also caused a significant increase in annexin-V-positive cells along with increased Fluo4 and DCF fluorescence and reduced FSC. Importantly, L-NAME, staurosporin, D4476, urea, sucrose, and polyethylene glycol 8000 (PEG) significantly ameliorated ZTN cytotoxicity. Conclusion: ZTN stimulates PS exposure, intracellular Ca²⁺ elevation, oxidative stress, and cell shrinkage. The hemolytic potential of ZTN, mediated through nitric oxide synthase/protein kinase C/casein kinase 1α signaling axis, is sensitive to isosmotic urea, sucrose, and PEG availability. Altogether, the anticancer potential of ZTN must be reconsidered with prudence.

Hibiscus mutabilis L (Malvaceae) was a traditional Chinese medicine with significant anti-inflammatory activity. We isolated 3 compounds from the flowers of H mutabilis L , including a new flavonoid, (1″R)-8-(1-(3,4-dihydroxyphenyl)ethyl)-3,3',5,7-tetrahydroxy-4'-methoxyl flavone (1), and 2 known flavonoids (2-3). The structures of these compounds were elucidated by various spectroscopic methods. In addition, we evaluated the anti-inflammatory effect of compound 1. The bioactivity assay showed that 1 significantly inhibit the excessive production of IL-6, TNF-α and NO in LPS-induced RAW264.7 macrophages. Western blot analysis demonstrated that 1 inhibit the expressions of COX-2 and iNOS protein in the macrophages induced by LPS in a concentration-dependent manner. In addition, 1 also significantly suppress the expression of the key proteins P65 and p-P65 in the NF-κB signaling pathway. Our results revealed that 1 exert potential anti-inflammatory activity through inhibiting the activation of NF-κB signaling pathway.

The Hiroshima/Nagasaki (H/N) studies by the Radiation Effect Research Foundation have not shown increased leukaemia for acute doses below 200 milli-gray (mGy). By contrast the INWORKS study of leukaemia in workers stated: "This study provides strong evidence of positive associations between protracted low-dose radiation exposure and leukemia". The INWORKS study also claimed increased leukaemia, not including Chronic Lymphocytic Leukaemia, at cumulative occupational doses of less than 100 mGy. This is contrary to the expectation that the H/N studies would show more severe effects than the worker study because the doses were acute instead of chronic and because the H/N studies included children who had higher rates of radiation induced leukaemia than adults. This paper shows that the INWORKS leukaemia study is consistent with the H/N studies in showing no increase in leukaemia in the low-dose range. In addition, any increase in leukaemia is confined to Chronic Myeloid Leukaemia, possibly from high radiation dose-rates or chemicals.

Background: Acacia nilotica is a multipurpose plant known for its remedial properties but the antimicrobial and hepatoprotective activity of its pods remained unexplored.

Objective: This study aimed to evaluate the antimicrobial and hepatoprotective activity of n-hexane (ANPH) and methanol (ANPM) extracts of pods to scientifically validate their medicinal claims.

Methods: After the pharmacognostic evaluation of pods, in vitro tests were carried out to estimate phenolic and flavonoid content and antimicrobial potential. In vivo experiments involved testing of both extracts (250 and 500 mg/kg) paracetamol (PCM)-induced hepatotoxicity model in rats. The molecular docking studies explored insights into the potential binding capabilities of the ligands with the specific target proteins.

Results: ANPH and ANPM were enriched with phenols and flavonoids and showed antimicrobial effects. In the hepatoprotective test, the rats chronically treated with extracts had a dose-dependent hepatoprotection as markers of liver functionality were notably reduced (P < 0.05). The in silico studies revealed strong binding interactions of ergost-5-en-3-ol and oxiranyl methyl ester 9-octadecenoic acid with target proteins for antibacterial activity and hepatoprotective activity, respectively.

Conclusion: The antimicrobial and hepatoprotective potential of pods might be due to their phenols and flavonoids. The Pyrogallol, Ergost-5-en-3-and 9-octadecenoic acid might be bringing these remedial benefits through antioxidant and anti-inflammatory effects.