Dose-Response最新文献

Objectives: Radiation Adaptive Response (AR) is a biological phenomenon in which exposure to low-dose radiation (LDR) enhances an organism's ability to withstand subsequent higher doses. This scoping review explores AR across multiple disciplines, summarizing evidence, identifying research gaps, and evaluating potential applications in cancer therapy, neurodegenerative disease management, space medicine, and pandemic response.

Methods: A comprehensive review of experimental/clinical studies on AR was conducted, focusing on molecular mechanisms, biological implications, biophysical modeling, and translational applications.

Results: In oncology, AR has shown promise in selectively protecting normal tissues during radiotherapy while sensitizing tumor cells, yet its effects remain cell-type dependent. LDR may manage neurodegenerative diseases by modulating oxidative stress and inflammation. In space medicine, AR-based astronaut selection has been proposed as a novel strategy to mitigate radiation risks during long-term space missions, although empirical validation is lacking. LDR therapy for managing COVID-19 pneumonia has been explored, but ethical concerns and long-term safety risks require further investigation.

Conclusion: Despite AR's potential, its clinical and spaceflight implementation requires mechanistic elucidation, standardized protocols, and rigorous studies. The risks of tumorigenesis, individual variability in AR, and potential immunomodulatory effects must be evaluated before widespread application. Moreover, inconsistent AR appearance complicates its study and clinical use.

In this study we used biosynthesis methods to create bimetallic nickel cobalt nanoparticles (Ni-Co NPs) utilizing seaweed. Before exposure to target cells, the characterization of Ni-Co NPs is done by UV-Vis spectrophotometry, EDX, SEM, TEM, the shape of g Ni-Co NPs are polygonal form and its size is measured 38.27 ± 3 nm. The cytotoxic effect of g Ni-Co NPs on HuH7 and HCT cells were determined by MTT and NRU assays. The cytotoxicity of NPs increased in a concentration dependent manner and it showed high cytotoxic effect on HCT-116 cells than HuH-7 cells. We determined IC₅₀ 24 h for HuH-7 and HCT -116 cells at 24 h, it was 65.84 and 24.73 μg/mL, respectively. ROS was elevated at higher concentration of Ni-Co NPs. LPO was increased at 16 μg/mL in HuH-7 cells and 19 μg/mL in HCT-116 cells. CAT was reduced in HCT-116 cells than HuH-7 cells high concentration of NPs. JC-1 staining, the loss of MMP in control, Ni-Co NPs exposed cell were evaluated. In HuH-7 and HCT-116 cells, maximum apoptotic cells were observed at high concentration. Apoptotic genes were expressed in both type cells. The above findings highlight the significance of Ni-Co NPs and useful in a number of cancer treatments.

Background: Previously the author was unable to develop a formal mathematical characterization of his probability-based hormetic relative risk (HRR) model for cancer prevention/elimination by absorbed doses (D) of ionizing radiation in the hormetic zone where D < D _t (population absorbed dose threshold for cancer induction).

Objective: To develop a formal mathematical characterization of the HRR model's disease prevention function DPF(D), which is the cancer prevention/elimination probability.

Approach: Use distributed (over a population) individual-specific, natural-defenses-enhancing (E) and suppressing (S) dose thresholds.

Results: DPF(D) is now mathematically characterized based on Weibull-type E and S thresholds distributions. The E thresholds predominate at very low radiation doses and the S thresholds predominate at higher doses just below D _t. This leads to a hormetic dose-response relationship for cancer relative risk RR(D) (= 1 - DPF(D)) for doses from zero (representing natural background radiation exposure) to dose D _t. The greatly improved HRR model is quite flexible and was applied to lung cancer and reticulum cell sarcoma prevention/elimination data from a study involving more than 15 000 gamma-ray exposed mice.

Conclusion: The System of Radiological Protection needs to be updated to account for health benefits rather than invalid LNT-hypothesis-based phantom radiation-caused cancers from radiation doses < D _t.

In comparing magnetic resonance imaging (MRI) and computed tomography (CT), it is often stated thata significant advantage of MRI is its lack of ionizing radiation, which may contribute to carcinogenesis. This article questions whether this concern is justified. First, the basis for the linear no-threshold (LNT) hypothesis, which suggests a carcinogenic potential of CT, is now considered weak. Historically, the foundation of the LNT model was not grounded in robust scientific data, and the epidemiological evidence indicating an increased cancer incidence in children undergoing CTscans is not scientifically reliable. Both MRI and CT examinations elevate reactive oxygen species, leading to DNA damage, chromosomal aberrations, and micronucleus formation. Following a single scan with either MRI or CT, the γH2AX index in human lymphocytes increased to a similar degree; however, the small amounts of DNA damage produced are efficiently repaired, thus not resulting in carcinogenesis. While it may be argued that ionizing radiation induces more complex DNA damage than electromagnetic fields, no studies have compared the quality of DNA damage between MRI and CT at clinically relevant exposure levels. Considering the effective defense mechanisms of living organisms, infrequent MRI and CT examinations do not appear to pose an increased risk of carcinogenesis.

Objective: To elucidate the role of NEDD4 in ionizing radiation (IR)-induced endothelial-mesenchymal transition (EndMT) and its molecular mechanism in radiation-induced lung injury (RILI), given the unclear regulatory pathways of EndMT in RILI pathogenesis.

Methods: IR-induced EndMT was observed during RILI in vivo and in vitro by immunohistochemical staining and Western blot analysis. Proteomics identified NEDD4 as a candidate, validated by RNA sequencing (RNA-seq) and quantitative real-time polymerase chain reaction (qRT‒PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis linked NEDD4 to PI3K-AKT signaling. Co-immunoprecipitation (Co-IP) confirmed NEDD4-ATM interaction.

Results: IR upregulated NEDD4 in endothelial cells, correlating with EndMT progression. NEDD4 overexpression enhanced ATM pathway activation, modulating genes upstream/downstream of ATM. Co-IP verified physical NEDD4-ATM binding, suggesting NEDD4 stabilizes ATM to promote EndMT.

Conclusion: Overall, our study shows that NEDD4 mediates EndMT to participate in RILI through the ATM signaling pathway, which may break new ground for understanding the occurrence and development of RILI.

Objectives: The primary objective of this experimental study was to evaluate the severity of the anxiolytic effect of Prospekta, a novel drug for treating cognitive, behavioral, and mental disorders, under different administration regimens. Methods: The pharmacological activity of Prospekta was studied in adult male Wistar rats using the open field test. The drug was administered once, twice, or three times daily over a period of five days. Results: The most pronounced anxiolytic effect was observed with twice-daily administration of Prospekta. This regimen led to an increase in the total distance travelled and enhanced exploratory behaviour, as indicated by a greater number of entries into the center and more time spent in the central zones of the open field arena. Conclusion: Given the nature of Prospekta's composition, the conventional concept of "dose" is not fully applicable. Therefore, the observed effects may result from the cumulative impact of each administration. Furthermore, as with several other drugs used in neurology and psychiatry, a non-linear relationship between the frequency of administration and the anxiolytic effect was established for Prospekta.

Objective: In the current work, we investigated and assessed the ability of the bioactive flavone linarin (LIN) to prevent asthma in the ovalbumin (OVA)-induced rat model.

Methods: The experimental rats' body weight and relative lung weight were measured after each treatment. Indices of oxidative stress in lung tissue and erythrocytes were assessed. Analyses were conducted on hematological assays, measurement of histamine release in BALF fluid, and inflammatory markers found in blood and BALF, including IL-4, IL-13, TNF-α, IFN-γ, and IgE levels. For histological examination, tissue samples were collected.

Results: Administration of LIN significantly increased the rats' body weight; however, their relative lung weight decreased. According to our findings, LIN significantly raised SOD, GSH, and CAT levels while suppressing MDA content. The administration of LIN resulted in a considerable reduction in IgE levels, cytokines, and hematological assay influx in the corresponding samples. Histological assessment showed that LIN treatment significantly maintained the anatomy of the lungs and decreased the infiltration of inflammatory cells.

Conclusion: The regulation of oxidative stress and the avoidance of pulmonary airway inflammation are two proposed methods by which LIN may reduce asthma symptoms.

Objectives: Nalidixic acid has been used as a potent antibiotic drug in the biomedical sciences. In this study, we assessed photochemical properties of nalidixic acid as well as its effect for photocytotoxicity, apoptosis, and genotoxicity on the mouse fibroblast (L929) cell line over the course of 24 h under the ambient UVB intensity. Methods: Reactive oxygen species such as singlet oxygen (¹O₂), superoxide anion radical (O₂ ^•-), and hydroxyl radical (^•OH) were measured by photochemical test and photocytotoxicity, apoptosis, and genotoxicity on the mouse fibroblast (L929) cell line were determined by various methods. Results: Furthermore, in UV-B irritated L929 cells, nalidixic acid decreased GSH and raised LPO levels compared to dark control cells. Nalidixic acid caused concentration-dependent toxicological effects (P < 0.05) in L929 cells when exposed to ambient UVB intensity (1.4 mW/cm²). DNA fragmentation and caspase-3 activity were observed to be significantly (P < 0.05) activated in L929 cells under co-exposure of UV-B and nalidixic acid. Conclusion: Our results thus confirm that when exposed to UVB rays, nalidixic acid exhibits both phototoxic and photo-genotoxic effects.

Objectives: To investigate the impact of chronic and low-dose ionizing radiation (IR) exposure on the workers' hematopoietic system. Methods: Hematological parameters in IR exposed healthcare workers (n. 180) were compared to those determined in unexposed controls (n. 180). The relationship with the 5-year cumulative doses: <0.45; 0.45-1.28 and >1.28 mSv, was assessed. Results: Red blood cells (RBCs), hemoglobin (HB) and hematocrit (HCT) showed significant differences compared to controls. A non-linear relationship was determined with respect to the cumulative doses. RBCs showed a significant decrease at the first <0.45 mSv IR-dose compared to controls (4.72 ± 0.31 vs 4.90 ± 0.38 × 10¹²/L; P = .013) with a rising trend, although not significant, at the two highest doses. Comparably, at the two lowest doses, HB (135.8 ± 11.3, P < .001 and 137.4 ± 10.1 g/L, P < .001) and HCT (41.8 ± 2.7, P < .005 and 41.7 ± 2.7%, P < .001) significantly decreased compared to controls (143.9 ± 10.6 g/L and 43.16 ± 2.95%, respectively), while not significantly increased at the >1.28 mSv highest one. Conclusions: IR exposure affected the hematopoietic system according to an hormetic phenomenon, intended as a biphasic dose-response with a low-dose stimulation and a high-dose inhibition, and, potentially, through a triphasic dose-response. These results deserve attention to define/implement suitable IR occupational risk assessment and management strategies.

Background: Liquid biopsy, analyzing the expression and variation of circulating tumor cell (CTC) or circulating tumor nucleic acid genes in peripheral blood, can obtain the information of tumorigenesis, metastasis and treatment, which has a potentially broader and complementary applications in the precision cancer medicine. Small vesicles, like exosomes which belongs to extracellular vesicles (EVs), which released by living cells into the vicinal surrounding biofluids, especially cells from carcinoma. Tumor-derived materials were contained by exosomes, totally including proteins, nucleic acid genes, and lipid, etcetera for instance metabolites. Besides, molecules which were synchronously belongings and carried on exosomal surface can tolerable provides crucial clues regarding their origin. Thus, classified the types of vesicles and enrich features from tissue-specific sources become presumably achieved. Therefore, exosomes and other EVs have emerged as a liquid biopsy platform for early screening and diagnosis of cancers, which constantaneously carry-over multitudinous surface molecules also throw clues regarding their origin. It is feasible to sort vesicles types, intake with approach channel to enrich the characteristics from tissue-specific origin. Based on the property that exosomes are remarkably stable in body fluids, which can amenity gathered in plasma or urine, it can be used for meticulous clinical evaluation particularly in the early stages of carcinoma. Therefore, exosomes have aroused immense interest in the study of biomarkers. Conclusions and Perspectives: This review aims to summarize the potential exosomal biomarkers especially exosomal miRNAs for exosome-based liquid biopsy in early screening and diagnostic of cancers, including lung cancer, breast cancer (BC), kidney cancer, prostate cancer (PCa), colorectal cancer (CRC), and summarizes the traditional and novel technologies for isolating exosomes and for detecting exosomal-based biomarkers, including exosomal proteins and exosomal nucleic acids. Finally, the limitations and prospects of exosome-based liquid biopsy in the early screening and diagnosis of cancers were discussed briefly.