Dose-Response最新文献

{"title":"The Roles and Implications of m6A Methylation in Radiotherapy for Gastrointestinal Tumors.","authors":"Jinling Bi, Wentao Hu, Huahui Bian, Wei Cheng","doi":"10.1177/15593258261418854","DOIUrl":"10.1177/15593258261418854","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"24 1","pages":"15593258261418854"},"PeriodicalIF":2.4,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12833114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146060835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Association Between Cobalt and Osteoporosis: A Cross-Sectional Study Utilizing NHANES Data.","authors":"He Liu, Yilong Hu, Jianmin Liu","doi":"10.1177/15593258261417145","DOIUrl":"10.1177/15593258261417145","url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 (<i>P</i> = 0.721).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"24 1","pages":"15593258261417145"},"PeriodicalIF":2.4,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12816526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibroblast Growth Factor 19 (FGF-19) Expression in Glycoresistant Human Umbilical Cord Mesenchymal Stem Cells (ghUC-MSCs) and Its Regulatory Effect on Glucose Metabolism in Insulin-Resistant Hepatocytes.","authors":"Chun-Xiang Liu, Ihsan Ullah, Yi Zhang","doi":"10.1177/15593258251412122","DOIUrl":"10.1177/15593258251412122","url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"23 4","pages":"15593258251412122"},"PeriodicalIF":2.4,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12744111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145855031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of the Mechanism of Action of the Mongolian Medicine Eerdun Wurile Basic Formula in the Treatment of Ischemic Stroke Through Transcriptomics and Metabolomics Integration.","authors":"Hong Xiao, Limuge Che, Yiri Du, Hashen Bao","doi":"10.1177/15593258251409844","DOIUrl":"10.1177/15593258251409844","url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>Compared with the sham operation group, the model group exhibited significant neurological deficits in rats (<i>P</i> < 0.01). Compared with the model group, EWB significantly reduced the Zea-Longa five-point neurological deficit score (<i>P</i> < .05, <i>P</i> < .001), improved rat survival rate (<i>P</i> < .01, <i>P</i> <.001), increased activity distance (<i>P</i> < .01) and activity time (<i>P</i> < .01, <i>P</i> < .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 (<i>P</i> < .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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"23 4","pages":"15593258251409844"},"PeriodicalIF":2.4,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12744113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145854992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radio-Protective Effect of Lanzhou Lily Polysaccharide on the Spleen in Mice.","authors":"Zhong Guo, Jin Zhao, Lina Lu, Jianxiu Ma, Yanqing Ma, Lei Song, Chenjing Wang, Zhiyuan Liu","doi":"10.1177/15593258251409856","DOIUrl":"10.1177/15593258251409856","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the protective effect and underlying mechanism of Lanzhou Lily Polysaccharide (LP) against radiation-induced splenic damage in mice.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>LP can protect mice from radiation-induced splenic damage.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"23 4","pages":"15593258251409856"},"PeriodicalIF":2.4,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12722676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginsenoside Rh2 Suppresses the Fanconi Anemia Pathway by Inhibiting NF-κB-Mediated FANCL Transcription in Bladder Cancer.","authors":"Chen Li, Guanglin Lv, Zhuang Xiong, Zhenfan Wang","doi":"10.1177/15593258251411761","DOIUrl":"10.1177/15593258251411761","url":null,"abstract":"<p><strong>Objectives: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"23 4","pages":"15593258251411761"},"PeriodicalIF":2.4,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12717414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145803467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dose-Dependent Cardioprotection of Pterocarpus indicus Extract in Rats With Myocardial Ischemia: Targeting Oxidative Stress, Inflammation, and Apoptosis.","authors":"Chen Yichun, Du Wen, Jin Weimeng, Fang Xin, Sun Fangyun","doi":"10.1177/15593258251404066","DOIUrl":"10.1177/15593258251404066","url":null,"abstract":"<p><strong>Background and aim: </strong>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.</p><p><strong>Experimental procedure: </strong>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.</p><p><strong>Results: </strong>P.indicus at MD and HD significantly attenuated ISO-induced ECG abnormalities, histopathological damage, serum injury markers, inflammatory cytokines, and fibrosis (all <i>P</i> < 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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"23 4","pages":"15593258251404066"},"PeriodicalIF":2.4,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12690059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145740799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dosimetric Effect of Thymus on Radiation-Induced Lymphopenia in Breast Cancer Patients Who Received Adjuvant Radiotherapy.","authors":"Tong Xia, Sisi Zheng, Jianjun Qian, Yinyin Yang, Liyan Jin, Guoqin Jiang, Peifeng Zhao, Yijia Hu, Shicheng Li, Liyuan Zhang, Ye Tian, Shang Cai","doi":"10.1177/15593258251406031","DOIUrl":"10.1177/15593258251406031","url":null,"abstract":"<p><strong>Background: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 <math><mrow><mo>≤</mo></mrow> </math> 1.5 <math><mrow><mo>×</mo></mrow> </math> 10⁹/L, thymus V5 <math><mrow><mo>≤</mo></mrow> </math> 52.76%, thymus V10 <math><mrow><mo>≤</mo></mrow> </math> 9.08%, MTD <math><mrow><mo>≤</mo></mrow> </math> 6.12 Gy, respectively.</p><p><strong>Conclusions: </strong>Thymic radiation dose correlated with severe lymphopenia in breast cancer radiotherapy. Prospective trials are needed to validate these dose constraints for clinical use.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"23 4","pages":"15593258251406031"},"PeriodicalIF":2.4,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12690058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145740852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"U-Shaped Dose-Dependent Modulation of Macrophages by Ginkgolide B Mitigates Systemic Inflammation in Septic Rats.","authors":"Zhaofeng Luo, Lan Ming, Jiamin Ji, Qian Huang","doi":"10.1177/15593258251406112","DOIUrl":"10.1177/15593258251406112","url":null,"abstract":"<p><strong>Objectives: </strong>This study delineates the U-Shaped Dose-Dependent Modulation of Ginkgolide B (GB) on macrophage function, highlighting its capacity to enhance bacterial phagocytosis and attenuate systemic inflammation in sepsis.</p><p><strong>Methods: </strong>RAW264.7 cells were co-cultured with GB, and flow cytometry was used to assess macrophage phagocytosis and polarization. Rats were divided into five groups: Healthy, cecal ligation and puncture (CLP), and three GB treatment groups. Survival was monitored over 7 days, and arterial blood was analyzed to assess acidosis. Histological examination was performed to evaluate organ damage, while ELISA measured inflammatory factors in blood and peritoneal lavage fluid (PLF). Finally, bacterial colony counts in the PLF were analyzed to assess peritoneal macrophage bacterial clearance capacity.</p><p><strong>Results: </strong>GB co-culture enhanced macrophage bacterial phagocytosis. GB treatment alleviated acidosis and improved survival in septic rats. It also reduced pro-inflammatory cytokines TNF-α and IL-6 while increasing anti-inflammatory IL-10 levels. GB injection decreased bacterial load in the PLF, indicating enhanced macrophage bacterial clearance.</p><p><strong>Conclusion: </strong>GB enhances macrophage phagocytic activity, improves bacterial clearance, increases the survival rate of septic rats, and reduces systemic inflammation.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"23 4","pages":"15593258251406112"},"PeriodicalIF":2.4,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12686377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145721549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth Restriction in Balb/c Mice Irradiated With X-Rays During Late Gestation: Role of Irradiation Timing, Dose Fractionation and Adaptive Response.","authors":"Shayenthiran Sreetharan, Trista King, Christopher Thome, Neelam Khaper, Douglas R Boreham, Sujeenthar Tharmalingam, Simon J Lees, T C Tai","doi":"10.1177/15593258251395327","DOIUrl":"10.1177/15593258251395327","url":null,"abstract":"<p><strong>Objectives: </strong>Exposure of the developing fetus to high doses of ionizing radiation during prenatal development can result in growth restriction of the fetus, or a reduction in offspring growth. The developmental stage of the offspring at the time of irradiation is of interest, in order to characterize any potential periods of sensitivity for radiation-induced growth restriction effects. The goal of the present study was the development of a mouse model of radiation-induced growth restriction, following X-ray irradiation during late gestation.</p><p><strong>Methods: </strong>Pregnant BALB/cAnNCrl mice were irradiated with different irradiation conditions from gestational day (GD) 14-17. Treatments included an acute dose of 1.82 Gy X-ray irradiation on GD 14, 15 or 16. The effects of dose fractionation were also studied with one group receiving 0.455 Gy x 4 daily fractions from GD 14-17 (cumulative dose of 1.82 Gy). Another group also received a pre-treatment with 61 mGy X-ray irradiation on GD 14, 24 h prior to the 1.82 Gy on GD 15, to test for the possibility of a radiation-induced adaptive response.</p><p><strong>Results: </strong>Evidence for growth restriction was observed in all irradiation groups, with the greatest degree of growth restriction observed in the 1.82 Gy on GD 14 group. Evidence for growth restriction was based on a reduced gestational weight gain by pregnant dams and significant decrease in fetal weight and length measurements. Evidence for an adaptive response was not observed in the present study, as the combination group had similar outcomes to the group that only received the 1.82 Gy challenge irradiation dose.</p><p><strong>Conclusion: </strong>The establishment of a mouse model of radiation-induced growth restriction during late gestation will facilitate the ability for future work into determining the precise cellular and physiological effects on offspring, and the development of future countermeasures to protect against such adverse effects.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"23 4","pages":"15593258251395327"},"PeriodicalIF":2.4,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12686383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145721522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}