Dose-Response最新文献

Purpose: The present study aimed to compare the dose distributions between conventional three-catheter intracavitary (IC) brachytherapy and combined intracavitary-interstitial (IC/IS) brachytherapy in the management of locally advanced cervical cancer (LACC).

Materials and methods: A retrospective dosimetric analysis was performed using data from 78 patients with cervical cancer who underwent high-dose-rate (HDR) brachytherapy. To evaluate the dosimetric advantages of IC/IS brachytherapy, patients were stratified into two groups: those treated with IC brachytherapy and those treated with IC/IS brachytherapy. Dosimetric parameters between the two groups were compared.

Results: In the IC/IS brachytherapy group, V150 values for the high-risk clinical target volume (HR-CTV) were significantly higher than those in the IC group (p < 0.001). Subsequent comparison of organ-at-risk (OAR) dosimetric parameters revealed that D_0.1cc, D₁cc, D₂cc, D₅cc, and D₁₀cc values for the bladder and sigmoid colon were significantly lower in the IC/IS group than in the IC group (all p < 0.05).

Conclusions: Compared with conventional IC brachytherapy, combined IC/IS brachytherapy provides superior HR-CTV coverage with higher doses while simultaneously reducing radiation exposure to the bladder and sigmoid colon, provided that the D90 dose constraint for the HR-CTV is met.

Introduction: Quercetin, a dietary flavonoid typically consumed as a glycoside, is available in supplements in its aglycone form. This aglycone form is the most studied in preclinical and clinical research because of its antioxidant, anti-inflammatory, and metabolic properties. Several clinical trials have demonstrated the benefits of quercetin for enzymatic, metabolic and cardiovascular health, approximately 60% of these studies fail to verify the actual concentration administered, generating uncertainty on their findings.

Objective: This study aimed to evaluate the concentration, stability, and cost-concentration of commercial quercetin nutraceutical formulations.

Methodology: The concentrations of five commercial brands were quantified by high-performance liquid chromatography. Stability was assessed over 6 months at both room temperature and 40°C.

Results: Only one brand contained the amount labeled; three contained approximately 80%, and one contained merely 14.8%. This study is the first to evaluate the long and thermal stability of quercetin in nutraceutical products, demonstrating that the active ingredient remains stable for at least 6 months. Brand C was identified as the most suitable option.

Conclusion: There was significant variability in the quercetin concentration of commercial supplements. These findings underscore the need for stricter regulatory oversight to ensure the quality, therapeutic efficacy, and safety of nutraceutical products.

Background: Post-traumatic joint contracture (PTJC), characterized by progressive fibrosis, is a frequent complication following joint injury. Nevertheless, the molecular mechanisms driving its progression remain elusive. To address this, our study aims to delineate the dynamic transcriptomic alterations during arthrofibrosis development and to identify potential biomarkers associated with PTJC.

Methods: A rat model of PTJC was established, and RNA sequencing was performed on joint capsules at 0, 3, 7, 14, and 28 days post injury. We then applied Mfuzz time-series clustering, WGCNA, KEGG pathway enrichment analysis, and PPI networks to pinpoint key genes and pathways involved. Cross-species validation was conducted using human transcriptomic data from the GSE135854 dataset.

Results: Progressive joint stiffness and fibrosis were observed, peaking at 28 days post-injury. Transcriptome analysis identified 1385 differentially expressed genes (DEGs). KEGG analysis revealed significant enrichment in processes such as "extracellular matrix (ECM)-receptor interaction," "focal adhesion," "cyclic Guanosine Monophosphate - Protein Kinase G (cGMP-PKG) signaling," and "vascular smooth muscle contraction". By integrating rat and human data, we identified COL4A3, COL4A6, COL4A5, and ITGA8 as consistently upregulated hub genes. Their elevated expression in fibrotic joint tissues was further validated using RT-qPCR and immunohistochemistry (IHC).

Conclusion: This study provides a comprehensive transcriptomic landscape of PTJC progression and highlights COL4A3/COL4A6/COL4A5 and ITGA8 as promising biomarkers and therapeutic targets for arthrofibrosis.

Objectives: To investigate the protective effect and mechanism of (-)-epigallocatechin-3-gallate (EGCG) against radiation-induced intestinal injury (RIII).

Methods: C57BL/6J mice were pretreated with 10 mg/kg EGCG for 10 weeks or 3 days before 10 Gy total body irradiation (TBI) or whole abdominal irradiation (WAI), focusing on survival, body weight, intestinal structure, inflammation, and gut microbiota. For mechanism exploration, peritoneal and RAW264.7 macrophages were pretreated with 0-50 μM EGCG before irradiation, followed by assessments of cell viability, inflammatory proteins, and related signaling.

Results: EGCG protects mice from TBI-induced toxicity and weight loss, and alleviates WAI-induced intestinal injury, characterized by preserved villus architecture and reduced crypt cell apoptosis. Mechanistically, EGCG inhibits RIII by suppressing pro-inflammatory cytokine production (TNF-α, IL-6) and maintains the composition of gut microbiota disrupted by irradiation. In vitro studies confirm EGCG directly regulates the release of radiation-induced inflammatory factors in macrophages via inhibiting toll-like receptor (TLR) signaling, independent of microbial effects. The radioprotective effect of EGCG is attributed to its dual actions: preserving macrophage function to dampen inflammatory responses and maintaining gut microbiota homeostasis.

Conclusion: These findings highlight EGCG as a potential therapeutic agent for RIII, offering a novel strategy to improve outcomes in irradiated patients.

Objective: This study aimed to establish a high-performance liquid chromatography (HPLC) method for the simultaneous quantification of six components in Zhuqi Piantan Granules, and to investigate the protective effect and underlying mechanism of Zhuqi Piantan Granules alone or combined with electroacupuncture on cerebral ischemia-reperfusion injury in rats.

Methods: Zhuqi Piantan Granules were extracted with 80% methanol. HPLC analysis employed a C18 column and gradient elution using acetonitrile and 0.3% phosphoric acid as the mobile phase. Modeled rats were randomly grouped, given corresponding interventions for 14 days, and evaluated for neurological function, cerebral infarct ratio, vascular density, brain histological changes (hematoxylin-eosin (HE) staining), and Angiopoietin-1/Tyrosine Kinase Receptor-2(Ang-1/Tie-2) protein expressions (Western Blotting).

Results: All six target components exhibited excellent linear relationships (r ≥ 0.9994). The average recoveries ranged from 97.1% to 99.5%. Both Zhuqi Piantan Granules alone and their combination with electroacupuncture improved neurological function, reduced infarct ratio, increased vascular density, alleviated brain pathological damage, and upregulated Ang-1/Tie-2 expressions-with the combined treatment showing superior efficacy.

Conclusion: The established HPLC method is reliable and suitable for Zhuqi Piantan Granules quality control. Zhuqi Piantan Granules alone or combined with electroacupuncture alleviates rat cerebral injury by activating the Ang-1/Tie-2 pathway to promote angiogenesis.

Recent articles and news blogs have been written about nuclear waste management, specifically focusing on the alleged hazards of iodine-129. Here, we objectively review the specific details of iodine-129 as a radiation hazard. In contrast with the alarmist tone of these recent papers and news items, we conclude that iodine-129 is not nearly as concerning as has been projected. Rather, it appears to be a classic case of "much ado about nothing".

Gastrointestinal malignancies, which arise from multiple etiological factors, are a global health burden due to their high incidence and mortality rates. Nearly all gastrointestinal cancers present genomic and epigenomic alterations that play a critical role in initiating and driving tumor progression. N6-methyladenosine (m6A) methylation, a key epigenetic modification in eukaryotic messenger RNA (mRNA), is pivotal for regulating various cellular biological processes and influences both the progression and prognosis of diverse diseases. In gastrointestinal cancers, m6A methylation is closely associated with tumor proliferation, invasion, metastasis, and radiosensitivity. This review aims to uncover the translational regulatory mechanisms mediated by m6A methylation in gastrointestinal cancers and to clarify its role in radiotherapy, as well as to identify potential molecular targets for improving the efficacy of radiotherapy in treating gastrointestinal tumors.

Objective: This study investigates the association between blood cobalt levels and osteoporosis prevalence in the general U.S. population, addressing critical gaps in understanding low-to-moderate environmental exposure effects.

Methods: We analyzed 2901 adults from NHANES 2017-2020. Blood cobalt concentrations were categorized into quartiles. Multivariable logistic regression, restricted cubic splines (RCS), and Boruta algorithm were employed to assess dose-response relationships, nonlinear associations, and demographic effect modifications, adjusting for sociodemographic, metabolic, and clinical covariates.

Results: Participants in the highest cobalt quartile showed 32% increased osteoporosis prevalence vs Q1 (OR = 1.32, 95% CI:1.06-1.86). RCS analysis revealed a nonlinear relationship with an inflection point at 0.12 μg/L. Significant effect modifications emerged across multiple strata: females exhibited 91% greater risk elevation than males (OR = 1.91 vs 1.24, p-interaction = 0.022), Non-Hispanic Black participants demonstrated 36-fold higher odds (OR = 36.54, 95% CI:7.17-186.28), and participants with 9-11 years education showed elevated risk (OR = 21.72, 95% CI:1.27-372.63, p-interaction = 0.009). Married individuals exhibited higher risk (OR = 2.08, 95% CI:1.14-3.82) compared to never-married counterparts, though marital status interaction was nonsignificant (P = 0.721).

Conclusions: Environmental cobalt levels below current safety thresholds may associate with elevated osteoporosis prevalence, particularly in females and Non-Hispanic Black populations. The nonlinear dose-response relationship (inflection point 0.12 μg/L) suggests threshold effects, advocating for revised biomonitoring standards and targeted screening in vulnerable subgroups.

Objective: This study aimed to investigate the expression of FGF-19 in human umbilical cord mesenchymal stem cells (hUC-MSCs) after high-glucose culture. Furthermore, its regulatory effect on glucose metabolism in induced insulin-resistant hepatocytes (IIRHCs) and the underlying mechanism were investigated.

Methods: ghUC-MSCs were obtained via acclimation culture of hUC-MSCs with 2 g/L glucose medium. Immunofluorescence and ELISA were used to detect FGF-19 expression in ghUC-MSCs. GOD-POD, RT-qPCR and Western blot techniques were used to determine the effects of ghUC-MSCs and FGF-19 on glucose uptake and insulin sensitivity in IIRHCs.

Results: The ghUC-MSCs efficiently expressed FGF-19 and promoted glucose uptake in IIRHCs. However, the FGF-19 receptor inhibitor (FGFR4-IN) significantly reduced ghUC-MSCs-induced glucose uptake in IIRHCs. Notably, FGF-19 and ghUC-MSCs did not influence the effect of insulin on glucose uptake in IIRHCs. Besides, ghUC-MSCs did not significantly increase the phosphorylation level of insulin receptors. Furthermore, ghUC-MSCs and ghUC-MSCs plus FGFR4-IN significantly increased the expression of Glucose Transporter 1 (GLUT1) in IIRHCs. Additionally, ghUC-MSCs significantly increased AKT/ERK phosphorylation in IIRHCs, but this effect was negated by FGFR4-IN1.

Conclusion: ghUC-MSCs can efficiently express FGF-19. ghUC-MSCs and FGF-19 can regulate hepatocyte glucose metabolism. However, this regulatory effect is not dependent on the insulin signaling pathway.

Objective: The Eerdun Wurile Basic Formula (EWB) of Mongolian medicine has been widely used for the prevention and treatment of ischemic stroke, but its mechanism of action remains unclear. In this study, we combined transcriptomics, metabolomics, and in vivo experiments to explore the therapeutic mechanism of EWB in ischemic stroke, providing a scientific basis for clinical treatment.

Methods: SD rats were divided into six groups: Sham operation group, MCAO/R group, MCAO/R + Nimodipine group, MCAO/R + EWB low-dose group (EWB-L group), MCAO/R + EWB medium-dose group (EWB-M group), and MCAO/R + EWB high-dose group (EWB-H group). The efficacy was evaluated using the Zea-Longa five-point neurological deficit score, rat survival rate, open field test, and Morris water maze test, along with hematoxylin and eosin (H&E) and TUNEL staining. Enzyme-linked immunosorbent assay (ELISA) was used to measure the expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Transcriptomics and metabolomics analyses were conducted to identify key genes and metabolites, and qRT-PCR and western blot (WB) were used to verify key targets and elucidate the mechanism.

Results: Compared with the sham operation group, the model group exhibited significant neurological deficits in rats (P < 0.01). Compared with the model group, EWB significantly reduced the Zea-Longa five-point neurological deficit score (P < .05, P < .001), improved rat survival rate (P < .01, P <.001), increased activity distance (P < .01) and activity time (P < .01, P < .001), showing a significant therapeutic effect on spontaneous behavior and learning and memory impairments in rats. ELISA results demonstrated that EWB significantly reduced the expression levels of pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α (P < .01), leading to a marked reduction in neuroinflammation. Combined transcriptomics and metabolomics analyses identified SLC17A6, SLC6A11, SLC6A9, ADORA1, and GNG7 as key molecular targets of EWB. These targets modulate downstream pathways, including synaptic vesicle cycling, tyrosine metabolism, and glycerophospholipid metabolism, through inflammatory mediators. Furthermore, qRT-PCR and western blot analyses confirmed that EWB mitigates inflammation and inhibits relevant metabolic pathways by regulating the gene and protein expression of these core targets.

Conclusion: In summary, this study revealed that EWB reduces neuroinflammation and protects against ischemic stroke by modulating SLC17A6, SLC6A11, SLC6A9, ADORA1, GNG7, and the NF-κB signaling pathway, as well as regulating metabolites such as adenosine monophosphate and succinic acid.