Dose-Response最新文献

Objectives: The purpose of this study was to examine the effect of hawthorn extract drink in mildly hypertensive and/or hyperlipidaemic Chinese patients. Methods: We performed a randomized double-blind placebo-controlled crossover study. Subjects who were randomly divided into 2 groups and asked to consume either hawthorn fruit extract drink or placebo with the same sugar content for 8-weeks with crossover to the alternative drink separated by a 4-weeks washout period. Adverse effects, lipid profile, fasting plasma glucose and blood pressure were recorded. Results: In 61 participants, body weight increased by mean (95% CI) 0.42 kg (-0.85, 1.69 kg) with the hawthorn drink and 0.94 kg (0.52, 1.36 kg) with placebo (P > .05). Systolic blood pressure and plasma total cholesterol increased significantly with both treatments and cholesterol sub-fractions showed no significant changes. Significant increases were seen in fasting plasma glucose with placebo. The increase in plasma glucose was reversed during the 4-week washout period. Conclusions: Although our results didn't show significant effects of hawthorn drink compared to placebo, there was a trend toward fewer adverse metabolic effects. A longer study with hawthorn fruit extract without additional calories would be useful to determine if beneficial effects occur in patients with mild hyperlipidaemia or hypertension.

Objective: Moringa oleifera Lam. (Moringaceae), has traditionally been used for various renal diseases including urolithiasis. Considering the therapeutic and nutritional values, the present study was designed to investigate the antiurolithiatic potential of M. oleifera leaves through in-vitro, in-silico and in-vivo approaches. Methods: Methanolic aqueous extract of M. oleifera. leaves (MoL.Cr) was prepared and screened for phytoconstituents through FTIR and HPLC analysis, while antioxidant potential was determined by DPPH assay. Crystal nucleation, aggregation and growth assays were carried out to ascertain the in-vitro inhibitory effects of MoL.Cr. Molecular docking was performed to analyze the interactions between phytoconstituents and targeted proteins (Glycolate oxidase, Albumin and Tamm-Horsfall). Whereas, ethylene glycol-induced urolithiasis model (1% ammonium chloride +0.75% ethylene glycol) was used for in-vivo study. Presence of alkaloids, phenols, glycosides and flavonoids was confirmed by FTIR and HPLC analysis. Results: MoL.Cr significantly inhibited the CaOx crystal nucleation, aggregation as well as growth and normalized urinary and serum parameters. Histological studies showed that MoL.Cr significantly restored hyperoxaluria-induced irregular epithelial lining, interstitial inflammation and dilated proximal tubules. Conclusions: Thus, M. oleifera demonstrated marked stone inhibiting potential which can be due to its antioxidant, lowering of urinary concentration of stone forming constituents and anti-crystallization effects.

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.