Dose-Response最新文献

Introduction: Cell repair dynamics are crucial in optimizing anti-cancer therapies. Various assays (eg, comet assay and γ-H2AX) assess post-radiation repair kinetics, but interpreting such data is challenging and model-based data analyses are required. However, ambiguities in parameter calibration remain an unsolved challenge. To address this, we propose combining survival dose-rate effects with computer simulations to gain knowledge about repair kinetics.

Methods: After a literature review, theoretical discriminators based on common fractionation/dose-rate-related effects were defined to discard unrealistic model dynamics. The Multi-Hit Repair (MHR) model was calibrated with canine osteosarcoma Abrams cell line data to study the discriminators' efficacy in scenarios with limited survival data. Additionally, survival dose-rate-dependent data from the human SiHa cervical cancer cell line were used to illustrate the survival behavior at diverse dose-rates and the capability of the MHR to model these data.

Results: SiHa data confirmed the validity of the proposed discriminators. The discriminators filtered 99% of parameter sets, improving the calibration of Abrams cells data. Furthermore, results from both cell lines may hint universal aspects of cellular repair.

Conclusions: Dose-rate theoretical discrimination criteria are an effective method to understand repair kinetics and improve radiobiological model calibration. Moreover, this methodology may be used to analyze diverse biological data using dynamic models in-silico.

Antibiotics are widely used in veterinary and human medicine, but these compounds, when released into the aquatic environment, present potential risks to living organisms. In the present study, the activated carbon (AC) used for their removals is characterized by FT-IR spectroscopy, BET analysis and Scanning Electron Microscopy (SEM) to determine the physicochemical characteristics. Response surface methodology (RSM) and Box-Behnken statistical design (BBD) were used to optimize important parameters including pH (2-12), temperature (20-45°C), and AC dose (0.05-0.20 g). The experimental data were analyzed by analysis of variance (ANOVA) and fitted to second-order polynomial using multiple regression analysis. The optimal conditions for maximum elimination of Amoxicillin (Amox) are (Dose: 0.124 g, pH 5.03 and 45°C) by applying the desirability function (df). A confirmation experiment was carried out to evaluate the accuracy of the optimization model and maximum removal efficiency (R = 89.999%) was obtained under the optimized conditions. Several error analysis equations were used to measure goodness of fit. Pareto analysis suggests the importance of the relative order of factors: pH > Temperature > AC dose in optimized situations. The equilibrium adsorption data of Amox on Activated Carbone were analyzed by Freundlich, Elovich, Temkin and Langmuir models. The latter gave the best correlation with q_max capacities of 142.85 mg/g (R² = 0.999) at 25°C is removed from solution. The adsorption process is dominated by chemisorption and the kinetic model obeys a pseudo-second order model (R² = 0.999).

Background: Buprenorphine (BPN) is a widely used analgesic in the pediatric population, although there are few studies on the pharmacokinetics and pharmacodynamics of this drug.

Objective: The objective was to characterize the pharmacokinetics of BPN after intravenous administration and analyze the effect of age, gender, weight, height, body mass index (BMI), and drug-drug interactions as covariates.

Methods: Ninety-nine children (2-10 years), who underwent orthopedic surgery under regional, general, or combined anesthesia were included. Patients evaluated according to the American Society of Anesthesiologists Physical Status Classification, who received intravenous BPN 2 μg/kg were enrolled. Blood was collected from 1-240 min. Drug plasma concentrations were determined by LC-MS/MS. Population pharmacokinetic parameters were obtained with Monolix 2021R1 software. Pearson's correlation and/or ANOVA were used for statistical analysis.

Results: Age was associated with changes in clearance and central compartment volume and the female gender was associated with lower intercompartmental clearance, while BMI modified clearance, central and peripheral compartment volume. Concomitant administration of BPN with fentanyl and dexamethasone produced decreases in clearance.

Conclusions: The covariates of sex, age, and BMI are directly related to the increase or decrease in BPN pharmacokinetic parameters.

Although it is well established that a vegetable-rich (Mediterranean) diet is associated with health benefits in later life, the mechanisms and biological origins of this benefit are not well established. This review seeks to identify the components a healthful diet that reduce the individual's suffering from non-communicable disease and extend longevity. We note the difference between the claims made for an essential diet (that prevents deficiency syndromes) and those argued for a diet that also prevents or delays non-communicable diseases and ask: what chemicals in our food induce this added resilience, which is effective against cardiovascular and neurodegenerative diseases, diabetes and even cancer? Working in the framework of acquired resilience (tissue resilience induced by a range of stresses), we arguethat the toxins evolved by plants as part of allelopathy (the competition between plant species) are key in making the 'healthful difference'. We further suggest the recognition of a category of micronutrients additional to the established 'micro' categories of vitamins and trace elements and suggest also that the new category be called 'trace toxins'. Implications of these suggestions are discussed.

This study focuses on the investigation of the significance of polymers in drug delivery approaches. The carboxymethyl cellulose (CMC), polyvinyl alcohol (PVA) and dextrin-based hydrogel membrane were prepared and employed for the sustained release of third-generation oral antibiotic (cefixime). Different proportions of CMC, PVA and dextrin were blended and hydrogel membranes were fabricated via solvent casting method. The prepared membrane was characterized by FTIR, SEM, UV-visible, TGA and swelling analysis. Cefixime drug was incorporated in the CMC/PVA/dextrin matrix and drug release was investigated. The sustained release of the tested drug (cefixime) was investigated and the drug was released in 120 min in the phosphate-buffered saline (PBS) solution. The antibacterial activity of the prepared membrane was promising against Proteus vulgaris, salmonella typhi, Escherichia coli and Bacillus subtilis strains. The swelling capabilities, thermal stability and non-toxic nature of the prepared CMC/PVA/dextrin membrane could have potential applications for cefixime drug in delivery in a controlled way for the treatment of infectious diseases.

Background and purpose: Artificial intelligence (AI) is a technique which tries to think like humans and mimic human behaviors. It has been considered as an alternative in a lot of human-dependent steps in radiotherapy (RT), since the human participation is a principal uncertainty source in RT. The aim of this work is to provide a systematic summary of the current literature on AI application for RT, and to clarify its role for RT practice in terms of clinical views.

Materials and methods: A systematic literature search of PubMed and Google Scholar was performed to identify original articles involving the AI applications in RT from the inception to 2022. Studies were included if they reported original data and explored the clinical applications of AI in RT.

Results: The selected studies were categorized into three aspects of RT: organ and lesion segmentation, treatment planning and quality assurance. For each aspect, this review discussed how these AI tools could be involved in the RT protocol.

Conclusions: Our study revealed that AI was a potential alternative for the human-dependent steps in the complex process of RT.

Objective: To investigate the biological role of miR-143 and miR-199a in mediating the progression of osteosarcoma (OS) by targeting cyclooxygenase (COX-2).

Introduction: COX-2 plays a crucial role in the development and progression of OS. However, the specific regulatory mechanisms of COX-2 in OS are still not well understood.

Methods: The expression levels of COX-2, miR-143 and miR-199a in OS tissues were detected using immunohistochemistry, qPCR, or western blot assays. The targeting relationship between miRNAs and COX-2 was determined. The effect of miRNA and COX-2 on OS cells was evaluated in vitro and in vivo.

Results: COX-2 expression was upregulated while miR-143 and miR-199a were downregulated in OS tissues. miR-143 and miR-199a suppressed the proliferation, migration, and invasion of OS cells. The dual-luciferase reporter gene assay showed that COX-2 was a direct target of miR-143 and miR-199a. Genetic knockdown of COX-2 significantly suppressed cell proliferation, induced apoptosis, and inhibited migration and invasion of OS cells. The expression levels of COX-2 and PGE2 were decreased after the overexpression of miR-143 and miR-199a. Additionally, COX-2 silencing inhibited the tumorigenesis of OS and the synthesis of PGE2 in vivo.

Conclusions: miR-143 and miR-199a/COX-2 axis modulates the proliferation, invasion, and migration in osteosarcoma.

This research investigated the anticancer properties of punicalagin, a prominent bioactive polyphenol extracted from Punica granatum L, in human gastric cancer cell lines. Normal and gastric cancer cells were exposed to different doses of punicalagin for various durations. Punicalagin exhibited cytotoxic effects on gastric cancer cells in a dose- and time-dependent fashion, while sparing normal gastric epithelial cells. It is noteworthy that among the 3 gastric cancer cells, HGC-27 cells were more resistant to punicalagin than 23,132/87 and AGS cells. Furthermore, punicalagin triggered apoptosis in gastric cancer cells, evidenced by a rise in both early and late apoptotic cell percentages. Western blot analysis further revealed that punicalagin elevated the levels of activated caspase-3. Conversely, punicalagin curtailed cell invasion and reduced the expression of MMP-2, MMP-9, Snail, and Slug. From a mechanistic standpoint, Western blotting indicated that punicalagin might inhibit the Erk and NF-κB pathways, leading to apoptosis induction and the inhibition of cell invasion in gastric cancer cells. These results indicate that punicalagin promotes apoptosis and inhibits cell invasion in gastric cancer cells by activating caspase-3 and suppressing MMP-2, MMP-9, Snail, and Slug through the inhibition of the Erk and NF-κB pathways.

Background: Arsenic (As) is a highly toxic and carcinogenic pollutant commonly found in soil and water, posing significant risks to human health and plant growth.

Objective: The objectives of this study to evaluate morphological, biochemical, and physiological markers, as well as ion homeostasis, to alleviate the toxic effects of As in sunflowers through the exogenous application of salicylic acid (SA), γ-aminobutyric acid (GABA), and their combination.

Methods: A pot experiment was conducted using two sunflower genotypes, FH-779 and FH-773, subjected to As stress (60 mg kg^-1) to evaluate the effects of SA at 100 mg L^-1, GABA at 200 mg L^-1, and their combination on growth and related physiological and biochemical attributes under As stress.

Results: The study revealed that As toxicity had a detrimental effect on various growth parameters, chlorophyll pigments, relative water content, total proteins, and nutrient uptake in sunflower plants. It also led to increased oxidative stress, as indicated by higher levels of malondialdehyde (MDA) and hydrogen peroxide (H₂O₂), along with As accumulation in the roots and leaves. However, the application of SA and GABA protected against As-induced damage by enhancing the enzymatic antioxidant defense system. This was achieved through the activation of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activities, as well as an increase in osmolytes. They also improved nutrient acquisition and plant growth under As toxicity.

Conclusions: We investigated the regulatory roles of SA and GABA in mitigating arsenic-induced phytotoxic effects on sunflower. Our results revealed a significant interaction between SA and GABA in regulating growth, photosynthesis, metabolites, antioxidant defense systems, and nutrient uptake in sunflower under As stress. These findings provide valuable insights into plant defense mechanisms and strategies to enhance stress tolerance in contaminated environments. In the future, SA and GABA could be valuable tools for managing stress in other important crops facing abiotic stress conditions.