Dose-Response最新文献

Objective: In the current work, we investigated and assessed the ability of the bioactive flavone linarin (LIN) to prevent asthma in the ovalbumin (OVA)-induced rat model.

Methods: The experimental rats' body weight and relative lung weight were measured after each treatment. Indices of oxidative stress in lung tissue and erythrocytes were assessed. Analyses were conducted on hematological assays, measurement of histamine release in BALF fluid, and inflammatory markers found in blood and BALF, including IL-4, IL-13, TNF-α, IFN-γ, and IgE levels. For histological examination, tissue samples were collected.

Results: Administration of LIN significantly increased the rats' body weight; however, their relative lung weight decreased. According to our findings, LIN significantly raised SOD, GSH, and CAT levels while suppressing MDA content. The administration of LIN resulted in a considerable reduction in IgE levels, cytokines, and hematological assay influx in the corresponding samples. Histological assessment showed that LIN treatment significantly maintained the anatomy of the lungs and decreased the infiltration of inflammatory cells.

Conclusion: The regulation of oxidative stress and the avoidance of pulmonary airway inflammation are two proposed methods by which LIN may reduce asthma symptoms.

Objectives: Nalidixic acid has been used as a potent antibiotic drug in the biomedical sciences. In this study, we assessed photochemical properties of nalidixic acid as well as its effect for photocytotoxicity, apoptosis, and genotoxicity on the mouse fibroblast (L929) cell line over the course of 24 h under the ambient UVB intensity. Methods: Reactive oxygen species such as singlet oxygen (¹O₂), superoxide anion radical (O₂ ^•-), and hydroxyl radical (^•OH) were measured by photochemical test and photocytotoxicity, apoptosis, and genotoxicity on the mouse fibroblast (L929) cell line were determined by various methods. Results: Furthermore, in UV-B irritated L929 cells, nalidixic acid decreased GSH and raised LPO levels compared to dark control cells. Nalidixic acid caused concentration-dependent toxicological effects (P < 0.05) in L929 cells when exposed to ambient UVB intensity (1.4 mW/cm²). DNA fragmentation and caspase-3 activity were observed to be significantly (P < 0.05) activated in L929 cells under co-exposure of UV-B and nalidixic acid. Conclusion: Our results thus confirm that when exposed to UVB rays, nalidixic acid exhibits both phototoxic and photo-genotoxic effects.

Objectives: To investigate the impact of chronic and low-dose ionizing radiation (IR) exposure on the workers' hematopoietic system. Methods: Hematological parameters in IR exposed healthcare workers (n. 180) were compared to those determined in unexposed controls (n. 180). The relationship with the 5-year cumulative doses: <0.45; 0.45-1.28 and >1.28 mSv, was assessed. Results: Red blood cells (RBCs), hemoglobin (HB) and hematocrit (HCT) showed significant differences compared to controls. A non-linear relationship was determined with respect to the cumulative doses. RBCs showed a significant decrease at the first <0.45 mSv IR-dose compared to controls (4.72 ± 0.31 vs 4.90 ± 0.38 × 10¹²/L; P = .013) with a rising trend, although not significant, at the two highest doses. Comparably, at the two lowest doses, HB (135.8 ± 11.3, P < .001 and 137.4 ± 10.1 g/L, P < .001) and HCT (41.8 ± 2.7, P < .005 and 41.7 ± 2.7%, P < .001) significantly decreased compared to controls (143.9 ± 10.6 g/L and 43.16 ± 2.95%, respectively), while not significantly increased at the >1.28 mSv highest one. Conclusions: IR exposure affected the hematopoietic system according to an hormetic phenomenon, intended as a biphasic dose-response with a low-dose stimulation and a high-dose inhibition, and, potentially, through a triphasic dose-response. These results deserve attention to define/implement suitable IR occupational risk assessment and management strategies.

Background: Liquid biopsy, analyzing the expression and variation of circulating tumor cell (CTC) or circulating tumor nucleic acid genes in peripheral blood, can obtain the information of tumorigenesis, metastasis and treatment, which has a potentially broader and complementary applications in the precision cancer medicine. Small vesicles, like exosomes which belongs to extracellular vesicles (EVs), which released by living cells into the vicinal surrounding biofluids, especially cells from carcinoma. Tumor-derived materials were contained by exosomes, totally including proteins, nucleic acid genes, and lipid, etcetera for instance metabolites. Besides, molecules which were synchronously belongings and carried on exosomal surface can tolerable provides crucial clues regarding their origin. Thus, classified the types of vesicles and enrich features from tissue-specific sources become presumably achieved. Therefore, exosomes and other EVs have emerged as a liquid biopsy platform for early screening and diagnosis of cancers, which constantaneously carry-over multitudinous surface molecules also throw clues regarding their origin. It is feasible to sort vesicles types, intake with approach channel to enrich the characteristics from tissue-specific origin. Based on the property that exosomes are remarkably stable in body fluids, which can amenity gathered in plasma or urine, it can be used for meticulous clinical evaluation particularly in the early stages of carcinoma. Therefore, exosomes have aroused immense interest in the study of biomarkers. Conclusions and Perspectives: This review aims to summarize the potential exosomal biomarkers especially exosomal miRNAs for exosome-based liquid biopsy in early screening and diagnostic of cancers, including lung cancer, breast cancer (BC), kidney cancer, prostate cancer (PCa), colorectal cancer (CRC), and summarizes the traditional and novel technologies for isolating exosomes and for detecting exosomal-based biomarkers, including exosomal proteins and exosomal nucleic acids. Finally, the limitations and prospects of exosome-based liquid biopsy in the early screening and diagnosis of cancers were discussed briefly.

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.