Dose-Response最新文献

The world's population continuous to shift towards older, less active and more sedentary lifestyles especially during middle age. In addition consumption of high-caloric diets, increases the risk of metabolic and cardiovascular afflictions. Developing clinical strategies to mitigate those health complications represent a difficult challenge. Our group has previously shown that combining metformin (MTF) and tert-butyl hydroquinone (tBHQ) treatments, in addition to exercise, partially prevents liver damage associated with obesity. Hence, we evaluated the role of exercise in combination with MTF and tBHQ (triple-treatment) to counteract mitochondrial damage in the liver from obese middle-aged female rats. Animals were fed a high-fat diet (HFD) starting at 21 days till 15 months of age. The treated groups performed a Fartlek-type exercise 5 days/week for 30 min/session. MTF and tBHQ were administered at a dose of 250 mg/kg/day, and 10 mg/kg/day, respectively, for 7 days/month from 10 to 15 months of age. Triple-treatment therapeutic approach promoted animal survival, and increased AMPK and PGC1α expression. Treatments increased mitochondrial ATP synthesis and OXPHOS complexes activities, recovered membrane potential, and decreased ROS production. In summary, exercise in combination with intermittent tBHQ and MTF treatments proved to be an excellent intervention to prevent mitochondrial damage caused by HFD.

Adsorption techniques are widely used to remove some classes of pollutants from waters, especially those which are not easily biodegradable. The removal of Methylene blue (MB), as a pollutant, from waste waters of textile, paper, printing and other industries has been addressed by the researchers. The aim of this study is to eliminate MB by Activated Coconut Shells (ACS) produced at low cost by adsorption in batch mode. The ACS was characterized by the FTIR spectroscopy and point of zero charge (pHpzc: 5.06). Some examined factors were found to have significant impacts on the MB uptake of ACS like the initial dye concentration C_o (40-120 mg/L), solution pH (2-8), ACS dose (1-12 g/L), agitation speed (50-500 r/min), particles size (1.0-1.2 mm) and temperature (298-333 K). The best capacity was found at pH 6 with an adsorbent dose 8 g/L, an agitation speed 200 r/min and a contact time of 60 min. Modeling Kinetics and Isotherms shows that the pseudo-second-order kinetic model with R ² (0.935 -0.998) and Langmuir adsorption isotherm model provide better fitness to the experimental data with the maximum adsorption capacity of 30.30 mg/g at 25°C. The separation factor R_L (0.933-0.541) in the concentration range studied (10-120 mg/L) shows a favorable adsorption. The isotherms at different temperatures have been used for the determination of the free energy ΔG^° (198-9.72 kJ/mol); enthalpy ΔH^° (82.082 kJ/mol) and entropy ΔS^o (245.689 J/K mol) to predict the nature of MB adsorption process. The positive values of (ΔG^o) and (ΔH^o) indicate a non-spontaneous and endothermic MB adsorption with a chemisorption. The adsorbent elaborated from Coconut Shells was found to efficient and suitable for the removal of MB dye from aqueous solutions, due to its availability, low cost preparation and good uptake capacity.

Objective: The modulating effects of Cucurbita pepo seed oil (CPSO) on dyslipidemia and neuronal dysfunction in tramadol toxicity were studied. Methods: Fifty-six albino rats were divided into seven groups of eight rats each after a 2-week acclimatization period. All animals had unrestricted access to water and feed, and treatments were administered orally once daily for 42 days. Glutamate dehydrogenase and glutaminase activities were assessed using brain homogenate, while lipid profiles were analyzed in serum samples. Results: Tramadol toxicity was evidenced by significant (P < 0.05) increases in brain glutamate dehydrogenase along with significant (P < 0.05) decreases in the activities of glutaminase in the group administered only tramadol. Also, serum levels of total cholesterol, LDL-C and triglycerides also increased significantly (P < 0.05) following administration of tramadol with decreased level of HDL-C (P < 0.05). However, treatment with CPSO significantly restored the activities and levels of the altered biochemical parameters in a dose-dependent manner. The results of the biochemical investigation using the lipid profile and the enzymes of glutamate metabolism were corroborated by the results obtained from the histopathological examination of the brain. Conclusion: The results of this study therefore suggest that tramadol-induced dyslipidemia and neuronal dysfunction be managed and prevented by the administration of Cucurbita pepo seed oil.

The duration and magnitude of haematological changes following non-targeted low-dose radiation have not been well explored. We previously reported that low-dose radiation (150 mGy 2x/week for 5 consecutive weeks) was well tolerated by participants (n = 15) with minimal toxicities and no changes in quality of life. Leukocytes, platelets and erythrocytes decreased from baseline measurement 12 months following treatment, however changes were not clinically significant. T-cells, NK-cells, B-cells and neutrophils were found to decrease during treatment and return to baseline levels by 3 months. The monocyte activation marker CD64 (FcγRI) was lower in participants whose cancer did not progress during the 12 month study follow up period, potentially giving insights into a biomarker of treatment success. Herein, we provide one of the most detailed descriptions of hematologic changes during low dose radiation treatment and during one year follow up. Low-dose radiation was associated with minor hematologic changes that mostly resolved by 3 months. (Clinical Trial Registered with the United States National Library of Medicine and National Institutes of Health under the title 'Low Dose Hemi-Body Radiation for Recurrent Prostate Cancer'; ID: NCT03196778).

Objectives: This study was conducted to determine the efficacy of mesenchymal stem cells (MSCs) or low-dose gamma radiation (LDR) on liver injury compared to the effect of olive leaf extract as a hepatoprotective agent.

Methods: Rats were allocated into six groups; group I served as the negative control. Group II received 5% dextran sodium sulfate (DSS) in its drinking water for 1 week. Group III was injected with a single dose of 1 × 10⁶ bone marrow-derived mesenchymal stem cells (BM-MSCs) intravenously. Group IV was treated as in group III after 5% DSS treatment. Group V was given 5% DSS, followed by olive leaf extract (OLE) (1000 mg/ kg, oral). Group VI: 5% DSS for 1 week, then was exposed to low-dose gamma radiation (LDR) (0.05 Gy).

Results: Rats treated with OLE, BM-MSCs, or exposed to LDR exerted significant alleviation in all hepatic biomarkers, significant enhancements in oxidative stress parameters, and improvements in inflammatory biomarkers Interleukin-1 beta (IL-1β) and Interferon gamma (INF-γ) hepatic contents compared with those of the DSS group. Histological pictures emphasized the biochemical findings.

Conclusions: BM-MSCs might be a valuable therapeutic approach to overcome hepatic injury. Exposure to LDR provided protective mechanisms that allow the body to survive better.

Background: Radiation-induced lung fibrosis (RILF) is a life-threatening complication of thoracic radiotherapy. Ferroptosis, a recently discovered type of cell death, is believed to contribute to RILF, though the associated mechanisms are unknown. This study aimed to investigate the potential mechanism of ferroptosis in RILF and examine the contribution of different cell types to ferroptosis during RILF progression. Methods: Histopathological changes in RILF lung tissue were assessed through H&E and Masson staining. IHC staining investigated ferroptosis markers (GPX4, ACSL4, NCOA4). Ferroptosis-related genes (FRG) and pathway scores were derived from RILF transcriptome microarray data. The sc-RNAseq analysis detected FRG score dynamics across cell types, validated by IF staining for PDGFR-α and ACSL4. Results: ACSL4 and NCOA4 protein levels were significantly higher and GPX4 lower in IR than control. FRG scores were positively correlated with fibrosis-related pathway scores in the RILF transcriptome data. FRG and ECM scores were concurrently upregulated in myofibroblasts. Enhanced co-staining of PDGFR-α and ACSL4 were observed in the fibrotic areas of RILF lungs. Conclusions: Our research indicated that in RILF, fibroblasts undergoing ferroptosis may release increased levels of ECM, potentially accelerating the progression of lung fibrosis. This finding presents ferroptosis as a potential therapeutic target in RILF.

Recently, there has been a radical change in understanding of the nature of drugs based on highly diluted solutions. It has been established that their activity does not depend on the content of the original substance in dilutions, but is a consequence of the technological processing (TP) of dilutions with vibration, which accompanies each dilution during the preparation of solutions and, among others, leads to the formation of nanoparticles with certain properties. Repeated vibration treatment leads to the appearance of modifying activity that is absent in the original substance, and these effects of TP solutions can be exerted without direct contact with their targets, which clearly indicates the physical nature of the TP solution's activity. In the framework of this article, a statistically significant effect of TP antibodies to the insulin receptor on glucose consumption by CHO cells both with and without contact exposure, as compared with control (P < 0.05) was shown in the vast majority of the experiments. The obtained results shed light on a possible source of activity of drugs based on TP antibodies, which should be associated with the applied vibration effect and can manifest itself both with contact exposure and without it.

This research aimed to evaluate the therapeutic effect of corilagin (Cor) against angiotensin II (Ang II)-induced cardiac fibrosis and its underlying mechanisms. C57BL/6 mice (male, 8-10 weeks) received saline or Ang II (2.0 mg/kg/day) via subcutaneous infusion and intraperitoneal injection of Cor (30 mg/kg) for 28 days. Ang II induction increased the fibrotic area, whereas Cor treatment inhibited the fibrotic area significantly. Cor markedly reduced the Ang II-induced cardiac fibroblasts. Cor significantly inhibited Ang II-induced increase in expressions of smooth muscle alpha-actin (α-SMA), collagen I, collagen III, transforming growth factor beta 1 (TGF-β1), fibronectin, and connective tissue growth factor (CTGF). Cor suppressed the intracellular reactive oxygen species (ROS) production. Cor therapy reduced Ang II-induced malondialdehyde (MDA) content, whereas superoxide dismutase (SOD) and catalase (CAT) activities were increased (all, P < .001). Moreover, Ang II induction elevated the expression of phosphorylated phosphatase and tensin homolog (p-PTEN), phosphorylated protein kinase B (p-AKT) (Ser473) and phosphorylated mammalian target of rapamycin (p-mTOR) (Ser 2448), whereas Cor reduced their expressions. Cor treatment inhibited the migration ability of the cardiac fibroblast, whereas a PTEN inhibitor, VO-ohpic, increased the migration capability. Cor could have a protective effect against Ang II-induced cardiac fibrosis via inhibition of the PTEN/AKT/mTOR pathway.