Dose-Response最新文献

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.

Objectives: To investigate the protective effect and underlying mechanism of Lanzhou Lily Polysaccharide (LP) against radiation-induced splenic damage in mice.

Methods: Mice were pretreated with LP before X-ray irradiation. (1) Antioxidant enzyme activities (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx)), glutathione (GSH) content, and levels of malondialdehyde (MDA), myeloperoxidase (MPO) in mice serum were measured using commercial kits; (2) The spleen index was calculated; (3) Hematoxylin-eosin (H&E) staining was performed to observe spleen morphology; (4) Splenocyte apoptosis and DNA damage were detected; (5) Immunohistochemistry and Western blotting were employed to detect DNA damage repair (eg, γ-H2AX) and apoptosis-related protein expression in splenic tissues.

Results: LP pretreatment alleviated irradiation-induced impairment of antioxidant capacity in mice, increased SOD, CAT, GPx activities and GSH content, decreased MDA and MPO levels. It reversed irradiation-induced reduction in spleen index. H&E staining showed LP mitigated radiation-caused splenic morphological damage. TUNEL assay demonstrated LP lowered the splenocyte apoptosis rate. Comet assay confirmed LP inhibited radiation-induced DNA damage in splenocytes. Immunohistochemistry and Western blotting results revealed LP down-regulated the expression of γ-H2AX and modulated DNA damage repair-related proteins, regulating apoptosis-related protein levels.

Conclusion: LP can protect mice from radiation-induced splenic damage.

Objectives: Cisplatin, a frontline chemotherapeutic agent for bladder cancer (BC), induces DNA interstrand crosslinks that are primarily repaired through the Fanconi anemia (FA) pathway. Hyperactivation of this repair mechanism contributes to cisplatin resistance, underscoring the need for FA-targeted sensitizers. This study investigated the effect of ginsenoside Rh2 on FA signaling and cisplatin sensitivity in bladder cancer cells.

Methods: Bladder cancer cell lines (T24, 5637, and RT4) were treated with cisplatin, with or without Rh2 pretreatment. FANCI/FANCD2 (ID2) complex monoubiquitination, FANCD2 foci formation, and interactions with downstream repair proteins (FANCP, FANCQ, PCNA) were examined. FANCL expression was analyzed at the transcriptional level, and rescue experiments were performed by FANCL overexpression. NF-κB signaling involvement was assessed using pharmacological agonists. A T24 xenograft model was used to validate in vivo efficacy.

Results: Cisplatin induced ID2 complex monoubiquitination, confirming FA pathway activation. Rh2 pretreatment abolished this modification and reduced FANCD2 foci formation, leading to persistent interstrand crosslinks without affecting intrastrand repair. Rh2 disrupted FANCD2- FANCP/FANCQ/PCNA interactions and selectively suppressed FANCL transcription. Overexpression of FANCL restored ID2 monoubiquitination despite Rh2 exposure. NF-κB agonists reversed Rh2-induced FANCL downregulation and FA inhibition. In vivo, Rh2 combined with cisplatin significantly reduced tumor growth in T24 xenografts, whereas NF-κB stimulation counteracted this effect.

Conclusion: Ginsenoside Rh2 suppresses NF-κB signaling to transcriptionally downregulate FANCL, thereby impairing FA pathway-mediated DNA repair and enhancing cisplatin cytotoxicity in bladder cancer. These findings highlight Rh2 as a potential combinatorial agent to overcome platinum resistance.

Background and aim: This study investigated the dose-dependent cardioprotective effects of Pterocarpus indicus extract (P.indicus; LD: 27, MD: 54, HD: 108 mg/kg) against isoproterenol (ISO)-induced myocardial ischemia in rats, focusing on oxidative stress, apoptosis, inflammation, and fibrosis.

Experimental procedure: Rats were pretreated for 14 days and divided into control, ISO, propranolol, and P.indicus (LD, MD, HD) groups. Myocardial injury was assessed via ECG, histopathology, serum biomarkers (CK-MB, LDH, cTnT, IL-6, IL-1β, TNF-α), oxidative markers (SOD, MDA, GSH-Px), and apoptosis-related proteins (Bax, Bcl-2, Caspase-3). Nrf2/HO-1 expression was analyzed by western blot. Phytochemical profiling was performed via UPLC-MS/MS and HPLC. Pharmacokinetics, safety, and therapeutic-regimen efficacy were also evaluated.

Results: P.indicus at MD and HD significantly attenuated ISO-induced ECG abnormalities, histopathological damage, serum injury markers, inflammatory cytokines, and fibrosis (all P < 0.01). Treatment suppressed oxidative stress (restored SOD/GSH-Px, reduced MDA) via Nrf2/HO-1 activation and inhibited apoptosis via Bax/Bcl-2/Caspase-3 modulation. The efficacy of MD (EC₅₀ ∼50 mg/kg) was confirmed by dose-response analysis. Pharmacological inhibition established that both Nrf2 activation and caspase-3 inhibition are necessary for P.indicus's effects. PK studies showed systemic exposure to key compounds (quercetin-3-O-glucoside, ferulic acid, linoleic acid), and a 14-day safety assessment revealed no hepatorenal toxicity. Post-injury therapeutic administration also conferred significant protection.

Conclusion: P. indicus extract confers dose-dependent cardioprotection against ISO-induced myocardial injury through dual modulation of the Nrf2/HO-1 and Bax/Bcl-2/Caspase-3 pathways, with the medium dose (54 mg/kg) identified as optimally effective and well-tolerated.

Background: Radiation-induced lymphopenia (RIL), particularly severe RIL (G3+), significantly impacts cancer outcomes. This retrospective study aimed to determine the role of irradiation dose to the thymus on RIL in breast cancer (BC) patients who received adjuvant radiotherapy (RT).

Methods: BC patients who received adjuvant RT in 2019 and had available complete blood count data were included. RIL was defined according to CTCAE v5.0 criteria. Logistic regression identified thymic dosimetric and clinical parameters linked to G3+ RIL, ROC analysis determined optimal protective thresholds, and Delong test compared model performance.

Results: The data of a total of 93 consecutive patients were retrospectively retrieved, with 37.6% (35/93) experienced G3+ RIL. Logistic regression analysis identified thymic dosimetric factors (mean dose, V5, V10), baseline ALC, RT technique and IMNI were associated with G3+ RIL. ROC analysis showed that a combined model of baseline clinical and thymic dosimetry parameters had the highest AUC (0.869). The optimal cutoffs for avoiding G3+ RIL were baseline ALC $\le$ 1.5 $\times$ 10⁹/L, thymus V5 $\le$ 52.76%, thymus V10 $\le$ 9.08%, MTD $\le$ 6.12 Gy, respectively.

Conclusions: Thymic radiation dose correlated with severe lymphopenia in breast cancer radiotherapy. Prospective trials are needed to validate these dose constraints for clinical use.