Dose-Response最新文献

Objectives: To investigate the correlation between Life's Essential 8 (LE8) and frailty in adults with asthma using data from National Health and Nutrition Examination Survey (NHANES).

Methods: We conducted a cross-sectional study by NHANES data (2001-2018) to assess the relationship between LE8 and frailty in asthma patients. Multiple logistic regression, restricted cubic spline (RCS) analysis, and subgroup analyses were performed to evaluate potential associations.

Results: Among the 3, 238 of 91 351 participants, 1066 asthma patients demonstrated frailty and 2172 asthma patients not. When comparing the groups with moderate and high LE8 scores to the group with low LE8 scores, the odds ratios (ORs) (95% confidence intervals) for frailty in asthma were 0.39 (0.27, 0.56) and 0.15 (0.08, 0.27),respectively. Every 10-point increment of LE8 scores was negatively correlated with frailty in asthma. Similar trends were observed for health behavior and health factor scores. ORs for frailty in asthma were 0.54 (0.41, 0.72) and 0.41(0.27, 0.64) when comparing the groups with moderate and high health behavior scores to the group with low health behavior scores. ORs for frailty in asthma were 0.68 (0.48, 0.98) and 0.50 (0.28, 0.88) when comparing the groups with moderate and high health factor scores to the group with low health factor scores. ORs for frailty in asthma were 0.78 (0.72, 0.84) both in the every 10-point increment of health behavior and health factor scores.

Conclusions: Higher LE8 scores, along with health behavior and health factor scores, were linearly and inversely associated with the prevalence frailty in adults with asthma, suggesting that improved LE8 may reduce frailty risk in asthma population.

Objectives: We aimed to explore the protective role of apigenin (API) and its underlying mechanisms in angiotensin II (Ang II)-induced hypertensive renal injury using both in vivo and in vitro models. Methods: In this study, we developed an Ang II-induced hypertensive renal injury mouse model and a recombinant IFN-γ-triggered murine podocyte clone 5 (MPC5) model in vitro. Results: API treatment reduced serum creatinine (Scr), blood urea nitrogen (BUN), and serum cystatin C (Cys-C) levels in Ang II-infused mice (all, P < .001). API reduced renal fibrosis and the expression of related molecules, including collagen I, collagen IV, fibronectin, transforming growth factor beta 1 (TGF-β1), and α-smooth muscle actin (α-SMA) (all, P < .001). The p-P13 K and p-Akt protein expression levels were improved by API treatment. API decreased the apoptotic rate, malondialdehyde (MDA) content, and mitochondrial ferrous iron, while increasing superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), which were reversed by treatment with the PI3K/Akt pathway inhibitor LY294002 (all, P < .001). In addition, API treatment reduced the expression of glutathione peroxidase 4 (GPX4) while enhancing SLC7A11 and ACSL4 expression, which was reversed by LY294002 treatment (all, P < .001). Conclusion: Our experimental data suggest that API inhibits cell ferroptosis by activating the PI3K/Akt pathway and alleviates renal injury caused by hypertension.

Objectives: To investigate the potential mechanisms of Nagab-9 in alleviating acute lung injury (ALI) by integrating network pharmacology analysis with in vivo and in vitro validation experiments.

Methods: Active compounds of Nagab-9 were identified using TCMSP and ETCM databases. ALI-related targets were collected from relevant disease databases, and an intersection of these targets was used to construct a protein-protein interaction (PPI) network to identify core targets. Functional analysis through Gene Ontology (GO) and KEGG pathway enrichment was performed. The key targets of Nagab-9 intervention in ALI were further validated in LPS-induced ALI mouse models and in mouse alveolar epithelial cell injury models.

Results: A total of 25 active components were identified from Nagab-9. PPI network analysis highlighted core targets, and GO and KEGG pathway analyses identified significant pathways involved. Six core components were selected based on topological parameters of the "compound-target-pathway-disease" network. In vivo, Nagab-9 was shown to alleviate ALI-induced lung damage, inhibit inflammatory infiltration, and modulate inflammatory factors by downregulating Ly6G, Cit-H3, and phosphorylated proteins SRC, ERK1/2, and STAT3 in lung tissue. In vitro experiments demonstrated that Nagab-9 effectively inhibits LPS-induced inflammatory responses, protecting lung tissue and suppressing neutrophil infiltration and NET formation, likely through the SRC/ERK1/2/STAT3 pathway.

Conclusion: Nagab-9 exerts a protective effect against ALI by modulating inflammatory responses and reducing neutrophil infiltration and NET formation, primarily via the SRC/ERK1/2/STAT3 signaling pathway. This study supports Nagab-9 as a promising therapeutic agent for ALI intervention.

Background: Sacubitril/valsartan is recommended for patients with New York Heart Association class II to III heart failure (class 1 recommendation). The objectives of the study were to evaluate the effectiveness and safety of metoprolol against sacubitril/valsartan in patients with heart failure and reduced ejection fraction (HFrEF).

Methods: In retrospective study, patients aged ≥18 years with heart failure and less than 40% of left ventricular ejection fraction received 25 mg metoprolol once daily (ML cohort, n = 117) or 50 mg sacubitril/valsartan twice daily (SV cohort, n = 128) for 6-months.

Results: Systolic and diastolic blood pressures, heart rates, N-terminal pro-brain natriuretic peptide values, and left ventricular ejection fraction values improved across both cohorts, especially in the ML cohort after treatments for 6-months as compared to before treatments (P < .05 for all). Death was higher in the SV cohort than in the ML cohort over 15 months (10 (8%) vs. 2 (2%), P = .0362). Fatigue, depression, shortness of breath, and wheezing have been reported in patients in the ML cohort. Dizziness, hyperkalemia, fatigue, abdominal or stomach pain, and blurred vision have been reported in patients in the SV cohort.

Conclusions: Metoprolol may offer superior safety with comparable efficacy.

Objective: In this study, we investigated the protective effect of Metformin on fibrosis of trabecular meshwork cells induced by TGFβ2.

Methods: Transformed and primary human trabecular meshwork cells (HTMCs) were treated with TGFβ2 or Metformin alone or combination, western blotting and immunofluorescence staining assays to detect autophagy activity and fibrotic proteins expression levels. TGFβ2 or Metformin alone or combination were injected into the anterior chamber of mouse eye. Mouse intraocular pressure (IOP) was measured every week, mouse eye sections were conducted immunofluorescence staining to analyze Col1 and Col3 expression. pSmad3 level and localization to evaluate TGFβ/Smad3 pathway activity. Chloroquine phosphate was used to block autophagy-lysosome pathway.

Results: Metformin activates autophagy of HTMCs in a dose dependent manner and efficiently ameliorates TMCs fibrosis induced by TGFβ2 in vitro and in mouse model, and decreased elevated IOP caused by TGFβ2. Metformin promotes fibrotic proteins degradation through the autophagy-lysosome pathway.

Conclusion: Our study found Metformin could alleviates fibrosis of HTMCs induced by TGFβ2 and decreased elevated IOP in mouse model.

Objectives: FLASH radiotherapy is garnering attention for its capacity to diminish skin toxicity without compromising tumoricidal efficacy, presenting a stark contrast to conventional (CONV) radiotherapy. Despite its promise, the underlying molecular mechanisms of FLASH irradiation (FLASH-IR) on skin are not yet fully elucidated.

Methods: This study investigated the transcriptomic responses of human foreskin fibroblast cells (HFF-1) via the FLASH-IR or CONV irradiation (CONV-IR), employing the next-generation RNA sequencing (RNA-seq) to capture the gene expression profiles. Our comparative analysis aimed to dissect the cellular and molecular pathways influenced by these two irradiation methods.

Results: We identified a spectrum of differentially expressed genes (DEGs), signaling pathways, and transcriptional networks that were either shared or divergent between FLASH-IR and CONV-IR. Particularly, transcription factor NR4A1 showed significant upregulation in response to FLASH-IR, while chromatin stability factor ELF3 was markedly downregulated following CONV-IR. The top 10 up-regulated DEGs were subjected to qPCR validation, confirming their differential expression in response to FLASH-IR and CONV-IR.

Conclusion: Collectively, our findings delineate unique regulatory landscapes of FLASH-IR and CONV-IR on skin cells, corroborating established effects and shedding new light on the molecular interplay within the context of ultra-high dose radiation.

Purpose: Nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial cytoprotective protein that shields cells from electrophilic and oxidative stress. Mice lacking Nrf2 exhibit heightened susceptibility to myelosuppression due to impaired hematopoietic reconstitution. In this study, we examined the altered sensitivity to ionizing radiation (IR) and 7,12-dimethylbenz(a)anthracene (DMBA) in Nrf2^-/- mice separately.

Materials and methods: Irradiate Nrf2^-/- or wild-type mice with a dose of 4 Gy to observe changes in body weight, survival rate, and blood routine at 12 months. DMBA was used to treat Nrf2^-/- and wild-type mice, and the body weight and survival rate of the mice were measured. The changes of heme oxygenase-1(HO1) and NAD(P)H: quinone oxidoreductase 1(NQO1) in mice treated with IR or DMBA were detected by RT-qPCR and western blotting.

Results: Our results indicate that Nrf2 deficiency leads to more severe blood and immune system injury in mice exposed to IR or DMBA. Additionally, long-term monitoring revealed that Nrf2 deletion resulted in more severe myelosuppression, leukemia-like symptoms, and higher cancer rates. At the mRNA and protein levels, there was no significant increase in HO1 and NQO1 levels in the Nrf2^-/- mice treated with IR or DMBA. These adverse effects might be attributed to the inhibited protein levels of HO1 and NQO1 and significant DNA damage in hematopoietic stem and progenitor cells (HSPCs).

Conclusions: We demonstrate that the genetic deficiency of Nrf2 in mice leads to reduced antioxidant capacity and suppression of hematopoietic and immune system function, resulting in increased sensitivity to IR or DMBA.

Purpose: This work was the first study to show the impact of γ- radiation on adropin levels in the serum and liver tissue of male albino rats.

Methods: Liver tissue and blood samples of rats were collected at 1, 3, 7 and 14 days after whole-body exposure to 7.5 Gy of γ-radiation.

Results: Irradiated groups revealed a marked decrease in adropin associated with a significant increase in STAT3 in the serum and gene expression. Furthermore, lipid profile (cholesterol, T.G, HDL, LDL, VLDL), liver function (AST, ALT, albumin and total protein), complete blood count (RBCs, WBCs, PLT, Hb, Hct%, MCH, MCV, WBCs differential), glucose and insulin were exhibited more noticeable alterations at all time periods of the experiment. In addition, data exhibited an obvious elevation in some inflammatory markers (IL-6) and TOS accompanied by a decline in the TAC.

Conclusion and future scope of work: γ- radiation has adverse effects on adropin that related inversely with STAT3, leading to further damage to liver cells as well as disturbances in lipid and glucose metabolism. Therefore, adropin could be used in people exposed to radiation such radiotherapy to control the serious effects of radiation. Further study is needed to confirm these results.

Objective: To evaluate the influencing factors of Vancomycin trough concentration in blood, construct an individualized Vancomycin administration model for rational use of Vancomycin. Methods: The clinical data of Vancomycin trough concentration in blood from June 2020 to December 2022 in our hospital were analyzed retrospectively. The effects of age, sex, Vancomycin administration and cumulative dose, albumin, total bilirubin, alanine aminotransferase, Creatinine (CR), urea (Bun), Creatinine clearance rate (Ccr), and time of blood sample collection on Vancomycin trough concentration were analyzed. A linear regression equation for the influencing factors of Vancomycin trough concentration in blood was constructed. Results: Sixty-six patients (82.5%) were treated with Vancomycin by intravenous drip. Significant differences existed in the influence of patients' age, Vancomycin administration, CR, Bun and Ccr on Vancomycin trough concentration (P < 0.05). Vancomycin trough concentration in blood showed negative correlated with Ccr (P < 0.05). The regression model of Vancomycin trough concentration in blood was y = 40.911 - 10.971 × method of administration - 1.715 × collection time + 1.018 × cumulative dose - 0.178 × Ccr, the model could predict 41.30% Vancomycin trough concentration in blood. Conclusion: The influencing factors of Vancomycin trough concentration in blood were complex. The constructed regression model of Vancomycin concentration in plasma may provide a scientific reference for individualized administration of Vancomycin in clinical practice.