Dose-Response最新文献

Objectives: This study aimed to explore the protective effects and underlying mechanisms of salidroside (SAL) in angiotensin II (Ang II)-induced hypertensive renal injury and fibrosis, using in vivo and in vitro models.

Methods: In this study, we generated Ang II-induced hypertensive renal injury and fibrosis in mice and the recombinant interferon-gamma (IFN-γ)-stimulated murine podocyte clone 5 (MPC5) model in vitro. Histological and oxidative stress analyses were performed to evaluate the renal injury.

Results: SAL pre-treatment reduced systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP), and attenuated serum creatinine (Scr), blood urea nitrogen (BUN), and serum cystatin C (Cys-C) levels in Ang II-infused mice (all, P < 0.001). SAL reduced renal fibrosis and related molecules expression, including Collagen I, Collagen III, and α-smooth muscle actin (α-SMA) (all, P < 0.001). SAL decreased the content of malondialdehyde (MDA) while increasing superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in Ang II-treated mice (all, P < 0.001). In addition, SAL pre-treatment inhibited AT1R, Wnt1, Wnt3a, and β-catenin expressions (all, P < 0.001), both in vivo and in vitro.

Conclusion: Our experimental data demonstrate that SAL pre-treatment protects against Ang II-induced hypertensive renal injury and fibrosis by suppressing the Wnt/β-catenin pathway in vivo and in vitro.

Objectives: The linear no-threshold (LNT) model, which has been used for radiation protection purposes, was developed based on the assumption that exposure to even a small amount of radiation may cause cancer. However, although it is known in carcinogenesis that there is variation in radiation sensitivity among individuals, the LNT model does not adequately consider radiosensitive subgroups. In this paper, we represent susceptibility to contract cancer by radiation exposure by means of the threshold of a dose-response function, introduce an assumption that the thresholds are random to represent the variation of the radiosensitivity among individuals in a susceptible subgroup. We propose a novel method, the random threshold (RT) model, for determining the safe dose limit for the subgroup to protect cancer-susceptible individuals from radiation exposure. Conclusion: The proposed method is illustrated by targeting ATM gene (a cancer-susceptible gene) mutation carriers as a radiosensitive subgroup. For cancer risk associated with low-dose radiation exposure, the contribution of radiosensitivity cannot be ignored, thus the RT model would be more suitable for risk protection for radiosensitive subgroups instead of the LNT model. We also notice that it could be widely applicable for risk protection of not only low-dose radiation but also environmental pollutants.

Objective: In this study, we investigated the cause of the AngII dose elevation in aqueous humor of primary open-angle glaucoma (POAG) patients.

Methods: Enzyme-linked immunosorbent assay (ELISA), western blotting were used to detect concentration of Angiotensin Converting Enzyme 2 (ACE2) and Prolylcarboxypeptidase (PRCP). AngII and AngII + Recombinant PRCP were injected into anterior chamber of mouse eye. Mouse Intraocular pressure (IOP) was measured every week, mouse eye sections were conducted Hematoxylin-and-Eosin (H&E) staining, Masson' staining and Immunofluorescence staining. Western blotting and Immunofluorescence staining assays to detected fibrosis of trabecular meshwork cells. Mass spectrometry was used to identify proteins of aqueous humor.

Results: PRCP dose are decreased in aqueous humor of POAG patients. There is a negative correlation between PRCP and AngII levels in aqueous humor and between PRCP levels and the IOP. PRCP treatment reverses fibrosis of trabecular meshwork (TM) and prevents IOP elevation induced by AngII. Exogenous PRCP rescues fibrosis induced by AngII in HTMCs. Proteome profiling detected 502 differentially expressed proteins.

Conclusion: Our study found PRCP dose was decreased in POAG patients' aqueous humor, and it might cause high level of AngII. Restoration of PRCP rescued fibrosis of TM cells and ameliorated IOP in AngII treatment mouse.

Objective: The investigation aimed to analyze the effect of Paeoniflorin (PF) on the initiation of atrial fibrosis and atrial fibrillation (AF) induced by angiotensin II (Ang II) and explore its associated underlying mechanism. Introduction: PF has anti-inflammatory, immunomodulatory, antioxidant, hepatoprotective, and hypolipidemic properties. However, the protective effect of PF against atrial fibrosis and AF remains unclear. Methods: Male C57BL/6 mice aged 8-10 weeks, with 40 individuals, were subjected to subcutaneous infusion of either saline or Ang II at a dosage of 2.0 mg/kg/day. Furthermore, PF at a dosage of 100 mg/kg/day was administered through gavage once daily for 28 days. Morphological, histological, and biochemical examinations were undertaken. AF was elicited through in vivo transesophageal burst pacing. Results: PF treatment significantly improved AF in Ang II-infused mice. In addition, PF attenuated cardiac hypertrophy, atrial fibrotic area, atrial apoptosis and oxidative stress in Ang II-induced mice. The effect of PF on the PI3K-Akt pathway reduced the expression of phosphoinositide 3-kinase (p-PI3K) and Phosphorylated Akt (p-Akt) in Ang II-induced mice. Conclusion: PF may, therefore, avert Ang II-induced atrial fibrosis and AF by inhibiting the PI3K-Akt pathway.

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Background: Dexamethasone in conjunction with type 3 serotonin receptor antagonists are being used to the prevention and treatment of chemotherapy-induced nausea and vomiting and postoperative nausea and vomiting in clinic. The present study aimed to investigates the stability of ramosetron with dexamethasone in infusions, with the goal of enhancing the safety and clinical applicability of their combined use.

Methods: Ramosetron hydrochloride (3.0 μg/mL) combining with dexamethasone (0.05, 0.1, 0.2 mg/mL) were prepared with 0.9% sodium chloride injection and then packaged in polyolefin bags or glass bottles. The stability were investigated kept in the dark at refrigeration for 14 days and at room temperature for 48 h.

Results: The concentration of both drugs maintained at least 97% in the various solutions for both storage conditions with light protection. In the light exposure conditions, as the extension of storage time, the concentration of both drugs had declined. All antiemetic mixture solutions remained clear and no changes in color, turbidity, precipitation, and the pH remained stable. The insoluble particles were in line with Chinese Pharmacopoeia.

Conclusion: Our findings suggest that combinations of ramosetron hydrochloride with dexamethasone sodium phosphate in 0.9% sodium chloride injection remain stable for 14 days at 4°C and 48 h at 25°C when protected from light.

Polyglutamine (PolyQ) diseases including Huntington's disease are devastating neurodegenerative disorders characterized by progressive neuronal loss and motor dysfunction. PolyQ pathology involves multiple cellular events and phytochemicals with multi-target mechanisms hold promise to treat these diseases with least side effects. One such promising phytochemical is Eugenol, which possesses antioxidant and anti-inflammatory properties, potentially targeting disrupted cellular pathways in PolyQ diseases. The present study investigated the effects of Eugenol on neurodegeneration and motor dysfunction in transgenic Drosophila models of PolyQ diseases. In this study, the robust pseudopupil assay was performed to analyze adult photoreceptor neuron degeneration, a marker of widespread degenerative events. Furthermore, the well-established crawling and climbing assays were conducted to evaluate progressive motor dysfunction in the PolyQ larvae and flies. This study found that Eugenol administration at disease onset or after progression reduced PolyQ disease phenotypes, particularly, neurodegeneration and motor dysfunction in a dose-dependent manner and with no side effects. Thus, this study suggests that Eugenol could be a viable candidate for developing treatments for PolyQ diseases, offering a multi-target approach with the potential for minimal or no side effects compared to conventional therapies.

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.