Dose-Response最新文献

Objectives: Cytokinins are plant hormones that regulate cell growth and differentiation. In particular, zeatin (ZTN) delays cellular senescence of human fibroblasts and keratinocytes and exhibits anticancer activity. Chemotherapy-induced anemia is a major side effect of anticancer therapy secondary to premature senescence of red blood cells (RBCs). Herein, we investigated the biochemical and molecular mechanisms underlying ZTN action in human RBCs. Methods: Colorimetric assays were used to quantify hemolysis and related markers and flow cytometric analysis was applied to examine eryptosis through phosphatidylserine (PS) exposure by annexin-V-FITC, intracellular Ca²⁺ by Fluo4/AM, reactive oxygen species (ROS) by H₂DCFDA, and cell size from forward scatter (FSC). Results: ZTN at 200 μM induced significant hemolysis and K⁺, Na⁺, AST, and LDH leakage. ZTN also caused a significant increase in annexin-V-positive cells along with increased Fluo4 and DCF fluorescence and reduced FSC. Importantly, L-NAME, staurosporin, D4476, urea, sucrose, and polyethylene glycol 8000 (PEG) significantly ameliorated ZTN cytotoxicity. Conclusion: ZTN stimulates PS exposure, intracellular Ca²⁺ elevation, oxidative stress, and cell shrinkage. The hemolytic potential of ZTN, mediated through nitric oxide synthase/protein kinase C/casein kinase 1α signaling axis, is sensitive to isosmotic urea, sucrose, and PEG availability. Altogether, the anticancer potential of ZTN must be reconsidered with prudence.

Hibiscus mutabilis L (Malvaceae) was a traditional Chinese medicine with significant anti-inflammatory activity. We isolated 3 compounds from the flowers of H mutabilis L , including a new flavonoid, (1″R)-8-(1-(3,4-dihydroxyphenyl)ethyl)-3,3',5,7-tetrahydroxy-4'-methoxyl flavone (1), and 2 known flavonoids (2-3). The structures of these compounds were elucidated by various spectroscopic methods. In addition, we evaluated the anti-inflammatory effect of compound 1. The bioactivity assay showed that 1 significantly inhibit the excessive production of IL-6, TNF-α and NO in LPS-induced RAW264.7 macrophages. Western blot analysis demonstrated that 1 inhibit the expressions of COX-2 and iNOS protein in the macrophages induced by LPS in a concentration-dependent manner. In addition, 1 also significantly suppress the expression of the key proteins P65 and p-P65 in the NF-κB signaling pathway. Our results revealed that 1 exert potential anti-inflammatory activity through inhibiting the activation of NF-κB signaling pathway.

The Hiroshima/Nagasaki (H/N) studies by the Radiation Effect Research Foundation have not shown increased leukaemia for acute doses below 200 milli-gray (mGy). By contrast the INWORKS study of leukaemia in workers stated: "This study provides strong evidence of positive associations between protracted low-dose radiation exposure and leukemia". The INWORKS study also claimed increased leukaemia, not including Chronic Lymphocytic Leukaemia, at cumulative occupational doses of less than 100 mGy. This is contrary to the expectation that the H/N studies would show more severe effects than the worker study because the doses were acute instead of chronic and because the H/N studies included children who had higher rates of radiation induced leukaemia than adults. This paper shows that the INWORKS leukaemia study is consistent with the H/N studies in showing no increase in leukaemia in the low-dose range. In addition, any increase in leukaemia is confined to Chronic Myeloid Leukaemia, possibly from high radiation dose-rates or chemicals.

Background: Acacia nilotica is a multipurpose plant known for its remedial properties but the antimicrobial and hepatoprotective activity of its pods remained unexplored.

Objective: This study aimed to evaluate the antimicrobial and hepatoprotective activity of n-hexane (ANPH) and methanol (ANPM) extracts of pods to scientifically validate their medicinal claims.

Methods: After the pharmacognostic evaluation of pods, in vitro tests were carried out to estimate phenolic and flavonoid content and antimicrobial potential. In vivo experiments involved testing of both extracts (250 and 500 mg/kg) paracetamol (PCM)-induced hepatotoxicity model in rats. The molecular docking studies explored insights into the potential binding capabilities of the ligands with the specific target proteins.

Results: ANPH and ANPM were enriched with phenols and flavonoids and showed antimicrobial effects. In the hepatoprotective test, the rats chronically treated with extracts had a dose-dependent hepatoprotection as markers of liver functionality were notably reduced (P < 0.05). The in silico studies revealed strong binding interactions of ergost-5-en-3-ol and oxiranyl methyl ester 9-octadecenoic acid with target proteins for antibacterial activity and hepatoprotective activity, respectively.

Conclusion: The antimicrobial and hepatoprotective potential of pods might be due to their phenols and flavonoids. The Pyrogallol, Ergost-5-en-3-and 9-octadecenoic acid might be bringing these remedial benefits through antioxidant and anti-inflammatory effects.

Background: Cyperus rotundus L., commonly known as nutsedge or purple nutgrass, is a resilient herb in the Cyperaceae family with notable pharmacological potential due to its diverse secondary metabolites. This study aimed to identify these metabolites and evaluate the antioxidant and enzyme inhibitory activities of the crude methanol extract of C. rotundus.

Methods: The crude methanol extract of C. rotundus was prepared, and its antioxidant activity was assessed using the DPPH scavenging assay. Additionally, in vitro inhibitory effects against the enzymes: α-amylase and α-glucosidase were evaluated. The secondary metabolites present in the extract were identified using ESI-MS/MS analysis.

Results: ESI-MS/MS analysis revealed the presence of various secondary metabolites, including rutin, quercetin, β-sitosterol, limonene, and beta-pinene. The crude methanol extract exhibited strong antioxidant activity and significant inhibition of α-amylase and α-glucosidase enzymes, which play crucial roles in carbohydrate digestion.

Conclusion: The findings indicate that the crude methanol extract of C. rotundus possesses notable antioxidant properties and the potential to inhibit key enzymes involved in carbohydrate metabolism. This study enhances our understanding of the bioactive compounds in C. rotundus and suggests its therapeutic applications for managing conditions related to carbohydrate metabolism.

Introduction: Radiation-induced lung fibrosis (RILF) is a common complication of thoracic radiotherapy. Metformin has been suggested to have a radioprotective effect. Objective: This study explored the radioprotective effects of metformin on RILF and its mechanisms. Methods: C57BL/6J mice were randomly divided into control, ionizing radiation (IR), low-dose metformin (L-Met), and high-dose metformin (H-Met) groups. The IR, L-Met, and H-Met groups received 15 Gy chest irradiation. The L-Met and H-Met groups were administrated 100 or 200 mg/kg metformin from 3 days before irradiation and continued for 6 months. The mice were then sacrificed, and samples were collected for further analysis. Results: RILF was induced in the irradiated mice. Metformin improved lung pathology, inhibited collagen deposition, and reduced inflammatory factors such as high mobility group box 1 (HMGB1), interleukin-1 beta, interleukin-6, tumor necrosis factor alpha in lung tissue, lavage fluid, and serum. Western blot and quantitative real-time PCR analyses revealed that metformin downregulated HMGB1, toll-like receptor 4 (TLR4), and nuclear factor kappaB (NF-κB) expression. Additionally, metformin reversed the irradiation-induced reduction in the abundance of Lactobacillus and Lachnospiraceae at the genus level. Conclusion: Our findings indicated that metformin ameliorates RILF by downregulating the inflammatory-related HMGB1/TLR4/NF-κB pathway and improving intestinal flora disorder.

Background: While respiratory rate has proven to be a sensitive prognostic indicator in ICU settings, its relevance in the context of Acute Myocardial Infarction (AMI) patients complicated by Congestive Heart Failure (CHF) remains underexplored. Therefore, this study aims to investigate the relationship between respiratory rate and in-hospital mortality in this specific patient cohort. Methods: This retrospective cohort study utilized the Medical Information Mart for Intensive Care-IV database to analyze all AMI patients with concomitant CHF. The primary outcome, in-hospital mortality, was assessed through multivariate analysis. Logistic regression models, restricted cubic spline regression models, and subgroup analyses were employed to explore the association between respiratory rate and in-hospital mortality. Results: The study encompassed 5056 participants diagnosed with both CHF and AMI. After adjusting for confounding variables, each incremental unit rise in respiratory rate was associated with an 8% increase in the risk of patient mortality (OR = 1.08, 95% CI: 1.05∼1.11, P < 0.001). When comparing individuals with respiratory rates in the first tertile (≤17 breaths per minute) and the third tertile (>17-20 breaths per minute) to those in the second tertile (17-20 breaths per minute), the adjusted ORs for in-hospital mortality were 1.09 (95% CI: 0.82∼1.46, P = 0.546) and 1.62 (95% CI: 1.27∼2.06, P < 0.001), respectively. A dose-response relationship depicted a J-shaped curve between respiratory rate and the risk of in-hospital mortality, with an inflection point at approximately 19 breaths per minute. Stratified analyses confirmed the robustness of this correlation. Conclusions: This study reveals a J-shaped association between respiratory rate and in-hospital mortality in ICU patients suffering from both AMI and CHF.

Backgound: Traumatic brain injury (TBI) is a severe neurological disorders, which invloving complicated molecular mechanisms, such as endoplasmic reticulum (ER) stress and ferroptosis. , However, the mechanism underlying TBI remains unclear.

Objectives: The Objective was to determine the effect of VPA on ER stress and ferroptosis, and affirm the relationship between ER stress and ferroptosis. Methods: The expression levels of GRP78, ATF6, CHOP and GPX4 in brain tissues were detected via western blot, histological staining, and immunofluorescence. The effect of VPA on ER stress and ferroptosis on OS cellswas evaluated in vitro and in vivo.

Results: In our study, we found that VPA suppressed ER stress after TBI by inhibiting the GRP78-ATF6-CHOP signaling pathway, which ameliorated ferroptosis by reversing the reduction of the ferroptosis protein GPX4. Furthermore, tissue defects, bleeding, and iron accumulation also reduced. Moreover, 4-phenylbutyric acid was used to further confirm our assumption.

Conclusion: VPA plays a neuroprotective role by inhibiting ER stress levels and subsequently inhibiting ferroptosis.

Background: For patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC), the current standard treatment is neoadjuvant chemoradiotherapy (nCRT) plus radical surgery. Objective: This study aimed to establish a predictive model, based on computed tomography (CT) radiomics features and clinical parameters, to predict sensitivity to nCRT in patients with ESCC pre-treatment. The goal was to provide risk stratification and decision-making recommendations for clinical treatments and offer more valuable information for developing personalized therapies. Methods: This retrospective study involved 102 patients diagnosed with ESCC through biopsy who underwent nCRT. To select radiomics features, we used the least absolute shrinkage and selection operator (LASSO) algorithm. A combined model was constructed, integrating the selected clinically relevant parameters with the Rad-Score. To assess the performance of this combined model, we utilized calibration curves and receiver operating characteristic (ROC) curves. Results: Nine optimal radiomics features were selected using the LASSO algorithm. The support vector machine (SVM) classifier was identified as having the best predictive performance. The area under the curve (AUC) of the SVM training group was 0.937 (95% CI: 0.856-1.000), and of the validation group was 0.831 (95% CI: 0.679-0.983). Smoking and alcohol history, neutrophil to lymphocyte ratio, serum aspartate aminotransferase to alanine aminotransferase ratio, and carcinoembryonic antigen and fibrinogen levels were independent predictors of sensitivity to nCRT in patients with ESCC. The AUCs of the combined model for the training and validation groups were 0.870 (95% CI: 0.774-0.964) and 0.821 (95% CI: 0.669-0.972), respectively. The calibration curve showed that the nomogram's predictions were close to the actual clinical observations, indicating that the model exhibited good predictive performance. Conclusion: Our combined model based on Rad-Score and clinical characteristics showed high predictive performance for predicting sensitivity to nCRT in patients with ESCC. It may be useful for predicting treatment effects in clinical practice and demonstrates the significant potential of radiomics in predicting and optimizing treatment decisions.

Objective: This paper explores the role of DNA methylation in α-irradiation damage at the cellular level. Methods: Human normal hepatocytes L-02 were irradiated using a 241 Am α source at doses of 0, 1.0, and 2.0 Gy. The methylation levels of the six differentially methylated genes were examined by pyrophosphate sequencing, and the mRNA expression levels of the six differentially methylated genes were examined by real-time fluorescence quantitative PCR. Results: The rate of γH2AX foci positive cells was significantly higher than that of the control group after irradiation of cells in different dose groups for 1 h and 2 h respectively (P < .05). The proportion of S-phase cells was significantly increased in the 1.0 Gy and 2.0 Gy dose groups compared with the control group (P < .05). The methylation levels of CDK2AP1, PDGFRL, PCDHB16 and FAS genes were significantly increased, while the mRNA expression levels were significantly decreased (P < .05). The expression levels of CDK2Apl, PCDHB16 and FAS were significantly negatively correlated with the methylation levels (P < .05). Conclusion: The α-particle radiation can affect gene expression at the epigenetic level, which led to the speculation that altered methylation levels of CDK2AP1, PCDHB16, and FAS genes may be involved in the α radiation damage process.