Dose-Response最新文献

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.

Introduction: Epilepsy is a neurological disorder characterized by recurrent seizures. Although antiepileptic drugs (AEDs) reduce the frequency of epileptic seizures, they can cause renal and hepatic damage. Several preclinical studies have indicated that Emblica officinalis Gaertn (AMLA) exerts an anticonvulsant effect related to its tannin and polyphenol content. Objective: We aim to evaluate the anticonvulsant effects of chronic oral AMLA administration and its impact on biochemical and hematological parameters in rats. Methods: Twenty-eight male Wistar rats (250 to 300 g) were divided into four experimental groups (n = 7): vehicle (purified water), AMLA (500 and 700 mg/kg), and carbamazepine (CBZ) (300 mg/kg) as the pharmacological control of anticonvulsant activity. Treatments were administered orally every 24 hours for 28 days, while carbamazepine was administered every 48 hours for 5 days before the behavioral, biochemical, and hematological test. On day 29, Status epilepticus (SE) was induced using the lithium-pilocarpine model (3 mEq/kg, i.p. and 30 mg/kg, s.c.), after which the behavioral and biochemical effects were evaluated. Results: The AMLA 500 mg/kg and CBZ 300 mg/kg groups presented fewer phase V seizures than the vehicle group did. None of the treatments modified biochemical or hematological parameters. Conclusion: AMLA could be considered as a potential alternative therapy for the treatment of epilepsy.

Introduction: Parkinson's disease (PD) is characterized by dopamine deficiency in the corpus striatum due to the degeneration of dopaminergic neurons in the substantia nigra. Symptoms include bradykinesia, resting tremors, unstable posture, muscular rigidity, and a shuffled gait. Thalictrum foetidum is traditionally used for neurodegenerative disorders. Objectives: This study aimed to explore the therapeutic potential of aqueous ethanolic extract of Thalictrum foetidum (AETF) against Parkinson-like symptoms and to investigate its underlying mechanism. Methodology: Thirty-six albino mice were randomly divided into 6 groups (n = 6): normal control, disease control, standard treatment (levodopa/carbidopa, 100/25 mg/kg), and 3 treatment groups (AETF at 200, 400, and 600 mg/kg). One hour before treatment, haloperidol (1 mg/kg, i. p.) was administered to induce Parkinson's disease in all groups except the normal control group. Results: Behavioral analysis showed significant improvement (P < .001) in motor function, muscular coordination, and reduced muscular rigidity and tremors. AETF also reduced oxidative stress. Histological examination of the brain showed reduced Lewy bodies, neurofibrillary tangles, and plaque formation. Conclusion: AETF alleviated PD symptoms by reducing neurodegeneration, modulating oxidative stress, and inhibiting the expression of nuclear factor-κB (NF-κB) and associated inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6).