Dose-Response最新文献

{"title":"Efficacy and Safety of Sintilimab in Combination With Anlotinib and Chemoradiotherapy as First-Line Treatment for Driver Gene-Negative Oligometastatic Non-small Cell Lung Cancer: A Real-World Cohort Study.","authors":"Jian Jiang, Chen Ni, Chunfeng Wu, Yu Song, Huiping Zhu","doi":"10.1177/15593258261476788","DOIUrl":"10.1177/15593258261476788","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to evaluate the efficacy and safety of sintilimab combined with anlotinib and chemoradiotherapy as first-line treatment for driver gene-negative oligometastatic non-small cell lung cancer (NSCLC).</p><p><strong>Methods: </strong>This retrospective study included patients with driver gene-negative oligometastatic NSCLC (single organ, ≤2 lesions) treated at the Affiliated Zhangjiagang Hospital of Soochow University (7/2021-12/2023). All patients received 4 cycles of sintilimab plus albumin-bound paclitaxel/carboplatin and achieved partial response or stable disease. Subsequently, patients received concurrent radical radiotherapy with or without anlotinib, or continued the original regimen. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events were analyzed.</p><p><strong>Results: </strong>A total of 88 patients were included: 27 in the sintilimab plus chemotherapy (SC) group, 32 in the sintilimab plus chemoradiotherapy (SCR) group, and 29 in the anlotinib plus sintilimab and chemoradiotherapy (ASCR) group. The radiotherapy group (SCR + ASCR) showed significantly longer median PFS and OS than the non-radiotherapy group (SC) (7.7 vs. 16.5 months, P < 0.001; 20.1 vs. 31.8 months, P = 0.004). The ASCR group had significantly higher 12-month PFS, 18-month OS, and 24-month OS rates than the SCR group (P = 0.005, 0.014, and 0.046, respectively). ORR and DCR were significantly lower in the non-radiotherapy group (P < 0.001 and P = 0.007). Treatment-related adverse events were manageable.</p><p><strong>Conclusion: </strong>In driver gene-negative oligometastatic NSCLC patients benefiting from first-line sintilimab plus chemotherapy, adding concurrent radical radiotherapy significantly improved survival with acceptable toxicity. The addition of anlotinib further enhanced long-term outcomes. These findings are preliminary and require prospective validation.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"24 3","pages":"15593258261476788"},"PeriodicalIF":2.8,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697338","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":"Prediction of the Dose and Dose-Rate of Ionizing Radiation that Provides the Greatest Biological Benefit.","authors":"Katsuhito Kino","doi":"10.1177/15593258261477574","DOIUrl":"10.1177/15593258261477574","url":null,"abstract":"<p><p>Because the existence of linear no-threshold (LNT) hypothesis in the low-dose region has not been confirmed, we previously proposed the \"hormesis-coupled LNT theory.\" Because this theory does not consider the effect of dose-rate, we applied our theory to different dose-rates using data from the previous reference (Yoshida et al. 2008). As a result, we calculated that the biological benefit via radiation can be observed at a dose-rate of <1 mGy/h. In the future, biologically beneficial factors may be identified by exploring the exposure region with cumulative doses of >350 mGy at this low-dose-rates.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"24 3","pages":"15593258261477574"},"PeriodicalIF":2.8,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697304","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":"Association of Type 2 Diabetes Mellitus and Risk of Colorectal Cancers in Pyogenic Liver Abscess.","authors":"Yen-Ying Wu, Yu-Feng Lin, Wai-Keung Chow, Yen-Chun Peng","doi":"10.1177/15593258261467135","DOIUrl":"10.1177/15593258261467135","url":null,"abstract":"<p><strong>Background: </strong>Pyogenic liver abscess (PLA) has been reported as a potential clinical marker for colorectal cancer (CRC). Patients with type 2 diabetes mellitus (T2DM) are generally considered at elevated risk for infections and cancers due to impaired immune function. However, the specific relationship between T2DM and CRC among individuals with PLA remains unclear.</p><p><strong>Methods: </strong>This retrospective cohort study was conducted using the TriNetX Global Collaborative Network. Adult patients (≥20 years) with PLA between 2010 and 2024 were identified and stratified by the presence of T2DM. Patients with amebic liver abscess were excluded. A 1:1 propensity score matching was performed to balance baseline characteristics between T2DM and non-T2DM groups, with standardized mean differences (SMD) <0.1 indicating adequate balance. The primary outcome was incident colon cancer (C18). The site-specific composite outcomes were right-sided colon and appendix cancer (C18.0-C18.4) and distal colorectal and anal cancer (C18.5-C21). The secondary outcome was all-cause mortality. Kaplan-Meier analyses with log-rank tests were used to compare cumulative incidence and survival between groups, and hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards models across multiple follow-up periods.</p><p><strong>Results: </strong>In this TriNetX-based retrospective cohort, 52,440 adults with PLA were identified, including 16,149 with T2DM. After 1:1 propensity score matching, 11,757 patients remained in each group with balanced characteristics (SMD <0.1). T2DM was not associated with an increased risk of overall colon cancer. Similar null associations were observed for the right-sided colon and appendix cancer composite and the distal colorectal and anal cancer composite., including at 3 months (HR 1.059, 95% CI 0.738-1.519), and remained non-significant at 5 years (HR 1.000, 95% CI 0.808-1.237). Findings were consistent across tumor locations. In contrast, T2DM was associated with higher all-cause mortality from 30 days (HR 1.181, 95% CI 1.051-1.326) to 5 years (HR 1.152, 95% CI 1.093-1.213).</p><p><strong>Conclusion: </strong>In patients with PLA, T2DM was not associated with an increased risk of overall colon cancer or either site-specific cancer composite. However, T2DM was consistently linked to significantly higher short- and long-term mortality, highlighting its adverse prognostic impact in this population.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"24 3","pages":"15593258261467135"},"PeriodicalIF":2.8,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13434325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148673187","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":"Peptidylprolyl Isomerase a Regulates DNA Damage Repair and Serves as a Prognostic Biomarker in Lung Adenocarcinoma.","authors":"Li Zou, Bixin Ren, Ying Wan, Xin Wang, Ruichi Shen, Wenlang Zhu, Limin Jin, Qiliang Peng, Ye Tian","doi":"10.1177/15593258261473591","DOIUrl":"10.1177/15593258261473591","url":null,"abstract":"<p><strong>Background: </strong>This study investigated the role of peptidylprolyl isomerase A (PPIA) in lung adenocarcinoma (LUAD) using bioinformatics approaches and experimental validation.</p><p><strong>Methods: </strong>This study began by assessing PPIA expression and its prognostic significance in LUAD. We then performed functional enrichment analyses and examined CNVs, DNA methylation, DNMT activity, RNA modification, immune cell infiltration, and drug therapy efficacy. Cellular experiments were performed to confirm the role of PPIA in DNA damage repair.</p><p><strong>Results: </strong>PPIA was overexpressed in LUAD tissues and was associated with poor prognosis, including shorter overall survival and progression-free interval. PPIA expression was correlated with CNVs, DNA methylation, DNMT activity, and RNA modification-related genes. It was also negatively associated with immune cell infiltration and immune-related gene expression, suggesting a potential immunosuppressive role. Drug sensitivity analysis indicated that PPIA may serve as a predictive biomarker for therapeutic efficacy in LUAD. In addition, PPIA expression was associated with DNA damage repair-related genes. Cellular experiments show that PPIA knockdown increases radiosensitivity and γ-H2AX foci formation, whereas PPIA overexpression exerts the opposite effects.</p><p><strong>Conclusion: </strong>This study highlights the potential of PPIA as a prognostic biomarker and target in LUAD, particularly in the regulation of DNA damage repair and tumor immune microenvironment remodeling.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"24 3","pages":"15593258261473591"},"PeriodicalIF":2.8,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590970","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":"Cnicin Attenuates Aluminium Chloride-Induced Neurodegeneration Through Antioxidant and Anti-Inflammatory Mechanisms.","authors":"Li Yu, Wardah A Alhoqail, Suresh Mickymaray, Fang Li","doi":"10.1177/15593258261471150","DOIUrl":"10.1177/15593258261471150","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a progressive neurodegenerative disorder with limited disease-modifying therapies. Aluminium chloride (AlCl₃)-induced neurotoxicity mimics key pathological features of AD, including oxidative stress, neuroinflammation, and cholinergic dysfunction.</p><p><strong>Objective: </strong>This study aimed to evaluate the neuroprotective effect of cnicin in an AlCl₃-induced rat model of Alzheimer-like neurodegeneration.</p><p><strong>Methods: </strong>Rats were divided into five groups: normal control, AlCl₃ control (75 mg/kg/day, p.o.), AlCl₃ with cnicin (20 and 40 mg/kg/day, p.o.), and AlCl₃ with donepezil (5 mg/kg/day, p.o.) for 30 days. Behavioral performance was assessed using hanging wire and beam walking tests. Biochemical parameters, including acetylcholinesterase (AChE), antioxidant enzymes (SOD, CAT, GSH), malondialdehyde (MDA), and inflammatory cytokines (TNF-α, IL-1β) were analyzed, along with histopathology.</p><p><strong>Results: </strong>AlCl₃ administration induced significant behavioral deficits, increased AChE activity, oxidative stress, neuroinflammation, and neuronal damage. Cnicin treatment dose-dependently improved motor function, reduced AChE activity, restored antioxidant levels, decreased lipid peroxidation, and suppressed inflammatory markers. Histological analysis confirmed preservation of neuronal architecture, comparable to that of donepezil.</p><p><strong>Conclusion: </strong>Cnicin exhibits significant neuroprotective effects against AlCl₃-induced neurodegeneration by modulating cholinergic activity, oxidative stress, and inflammation, suggesting its potential as a therapeutic agent for AD.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"24 3","pages":"15593258261471150"},"PeriodicalIF":2.8,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13400938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591007","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 Reconstruction After a WD‒XRF Spectrometer Accident Using Minute-Rate TLD Measurements.","authors":"Yiying Gao, Haoyu Wang, Ling He, Liangguo He, Wantian Wang, Linyu Li, Yurou Zhang, Yuxing Xue, Shuyu Zhang, Deming Liu","doi":"10.1177/15593258261471512","DOIUrl":"10.1177/15593258261471512","url":null,"abstract":"<p><p>Accurate dose estimation following radiation accidents remains challenging, particularly when personal dosimeter data are unavailable. This study presents a practical post-accident dose reconstruction approach based on minute-rate thermoluminescent dosimeter (TLD) measurements combined with exposure scenario reconstruction, demonstrated through a wavelength-dispersive X-ray fluorescence (WD‒XRF) spectrometer accident. The exposure scenario was reconstructed by placing LiF(Mg,Cu,P) TLDs at seven representative positions corresponding to head and hand locations, with the spectrometer operated under the recorded technical parameters (40 kV, 7 mA). Minute personal dose equivalent rates, <i>H</i> _p'(10), were measured and combined with reconstructed retention times to calculate cumulative doses, from which skin absorbed doses were derived. The measured dose rates ranged from 0.13 to 358.38 mSv/min for the head and from 0.07 to 620.24 mSv/min for the hands. The resulting cumulative skin absorbed doses were 7.58 Gy for the head and 12.52 Gy for the hands, consistent with reported dose ranges associated with localized radiation injury. This approach provides a feasible supplementary strategy for retrospective dose reconstruction under emergency or resource-limited conditions when conventional dosimetric information is unavailable.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"24 3","pages":"15593258261471512"},"PeriodicalIF":2.8,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148583779","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":"Integrating Network Pharmacology and Experimental Validation Reveals EGFR/PI3K/Akt Axis Mediates Ibrutinib-Induced Cardiotoxicity.","authors":"Yingxia Guan, Jiaqi Mei, Yuanqiao He, Mei Lu, Biao Cheng, Xinjin Zhang","doi":"10.1177/15593258261471515","DOIUrl":"10.1177/15593258261471515","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to systematically explore the molecular mechanism underlying ibrutinib-induced cardiotoxicity.</p><p><strong>Methods: </strong>Network toxicology was applied using DrugBank, PharmMapper, GeneCards, OMIM, and TTD databases to identify overlapping targets between ibrutinib and myocardial injury, followed by PPI network construction (STRING; confidence ≥0.7) and GO/KEGG enrichment analyses (Metascape). Molecular docking (AutoDock Vina) verified ibrutinib's binding affinity to core targets. In vitro, H9C2 cardiomyocytes were exposed to ibrutinib (0, 10, 20, 40, and 80 μM) for 24 h; CCK-8, DCFH-DA, EdU, and Calcein-AM/PI assays were performed to assess cell viability, ROS levels, proliferation, and cell death, respectively. Western blot analyzed phosphorylation of EGFR/PI3K/Akt/mTOR pathway proteins.</p><p><strong>Results: </strong>A total of 42 overlapping targets were screened from 337 ibrutinib-related targets and 471 myocardial injury-related genes. PPI network analysis identified EGFR, AKT1, SRC, ESR1, and CASP3 as hub genes, and KEGG enrichment analysis identified the PI3K-Akt pathway as the most significantly enriched cascade. Molecular docking confirmed that ibrutinib stably bound BTK and EGFR with a binding energy of -30.2 kcal/mol and formed multiple hydrogen bonds and salt bridges (2.2-3.2 Å). In H9C2 cells, ibrutinib dose-dependently reduced viability (IC50 = 119.49 μM), increased ROS production (40 and 80 μM), inhibited proliferation (10 and 20 μM), and promoted cell death (5 and 10 μM). Western blot confirmed that ibrutinib significantly downregulated phosphorylation of PI3K p85, Akt (Ser473), mTOR (Ser2448), and p70S6K (Thr389) without altering total protein expression.</p><p><strong>Conclusion: </strong>Ibrutinib induces cardiotoxicity by targeting BTK/EGFR and inhibiting the downstream EGFR/PI3K/Akt/mTOR pathway, providing a mechanistic framework for clinical safety management of BTK inhibitors.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"24 3","pages":"15593258261471515"},"PeriodicalIF":2.8,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148583818","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":"Mechanistic Insights Into Dose-Dependent Alleviation of Colorectal Cancer Through Artemisinin-Loaded Mesoporous Silica Nanoparticles in 1,2-Dimethylhydrazine-Induced Albino Wistar Rats.","authors":"Fatima Zahid, Umair Ilyas, Sara Zahid, Faisal Gulzar, Sampath Chinnam, Abdul Malik, Sara Aiman, Abdul Qayyum","doi":"10.1177/15593258261472123","DOIUrl":"10.1177/15593258261472123","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The current study investigates the suitability of encapsulating the Artemisinin-plant-originated lipophilic drug molecule into polyethylene glycol-coated mesoporous silica nanoparticles in a suitable dose regimen for the specific targeting of the drug in colorectal cancer.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methodology: &lt;/strong&gt;Mesoporous silica nanoparticles (MSNPs) were synthesized through the sol-gel method, and Artemisinin was loaded. Then characterization of Artemisinin-loaded mesoporous silica nanoparticles coated with polyethylene glycol (MSN-PEG@Artemisinin) was performed by Fourier transform infrared spectroscopy (FTIR), Zeta analysis, Polydispersity index (PDI) and X-Ray diffraction (XRD) techniques and compared with the standard drug Gemcitabine. The in vivo analysis of 1,2-dimethylhydrazine (DMH) was used to induce colorectal tumors in the colon of inbred male Wistar rats. The treatment group of rats was administered MSN-PEG@Artemisinin through intraperitoneal injection. Hematoxylin and eosin staining were performed to the histopathological examination of tumors.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The average size of MSN-PEG@Artemisinin was 203.6 ± 64.78 nm with a zeta potential of -10.9mV. PDI was measured at 0.106. FTIR analysis also supported the successful loading of Artemisinin in mesoporous silica nanoparticles with PEG coating without showing interactions. The encapsulation efficiency (EE) and Drug loading (DL) percentages were 82.75% and 33.10%, respectively. XRD indicated a uniform mesoporous structure with a proper hexagonal symmetry. The &lt;i&gt;in-vitro&lt;/i&gt; release was carried out in phosphate buffer with 7.4 pH following biphasic system with 26% drug release during the first 2.5 hours and 57% in 24 hours, indicating a good controlled release rate. &lt;i&gt;In-vivo&lt;/i&gt; study revealed DMH-induced colorectal rats showed the increased tumor weight (34.8±0.75mg) tumor length (8.2±0.6) and tumor width (6.0±0.5) at a dose level of 0.5 ml/kg. Artemisinin loaded MSNPs significantly (p &lt; .005) suppressed tumor weight (15.6±1.56), tumor length (5.7±0.23) and tumor width (2.3±0.8) at a dose level of 100 mg/kg body weight. Overexpression of 8-OHdG, MMP-7, CA-19-9, KRAS, IL-8, Caspase-8, PD-1 and PDL-1 in CRC, which were successfully treated with MSN-PEG@Artemisinin and standard Gemicitabine ((p≥0.056). MSNPs-PEG@Artemisinin suppressed DMH-induced colorectal carcinogenesis by targeting oxidative stress, KRAS/MMP-7/IL-8 inflammatory signaling, PD-1/PD-L1-mediated immune evasion, and Caspase-8-associated apoptotic dysregulation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;These results highlight the potential of modified MSNPs as a versatile drug delivery system for colorectal cancer, providing a viable approach to enhance the therapeutic window of Artemisinin by controlling the dose while reducing the adverse effects of cancer therapies. This research contributes to advancements in pre-clinical studies and to improvements in targeted colorectal ca","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"24 3","pages":"15593258261472123"},"PeriodicalIF":2.8,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148583768","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":"Impact of a Short-Term High-Fat Diet on Lifespan and Tumorigenesis After Early-Life Exposure to Radiation.","authors":"Yi Shang, Takamitsu Morioka, Yoshiko Amasaki, Chizuru Tsuruoka, Masaaki Sunaoshi, Hiromi Yanagihara, Keiji Suzuki, Shizuko Kakinuma","doi":"10.1177/15593258261469760","DOIUrl":"10.1177/15593258261469760","url":null,"abstract":"<p><strong>Introduction: </strong>Children are highly susceptible to radiation's carcinogenic effects. Lifestyle, in particular, diet-induced obesity (DIO) is closely linked to cancer risk factors. Most prior studies, however, have concentrated on the impact of long-term lifestyle factors.</p><p><strong>Objective: </strong>We assessed the impact of a short-term, high-fat diet (HFD) during young or adult on lifespan shortening and tumor development after infant radiation exposure.</p><p><strong>Methodology: </strong>B6C3F1 male mice were irradiated at 1 week of age with 4 Gy of gamma rays or did not undergo irradiation (0 Gy). After weaning, they were assigned to HFD or normal-fat diet (NFD) for four weeks during young (4-8 weeks old) or adult (20-24 weeks old) stages. Body weight measurement, plasma biochemical analysis, lifespan analysis, and histopathological analysis for tumor diagnosis were carried out.</p><p><strong>Results: </strong>A temporary gain of body weight and hyperlipidemia were observed in mice fed the HFD. Although short-term HFD intake had limited impact on lifespan shortening and tumor development, a short-term HFD at a young age significantly increased spontaneous hepatocellular carcinoma (HCC) risk.</p><p><strong>Conclusion: </strong>The influence of a short-term HFD on DIO-associated cancer, such as HCC, should be specifically noted. Lifestyle normalization has potential for reducing cancer risk.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"24 3","pages":"15593258261469760"},"PeriodicalIF":2.8,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13392318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148577159","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":"Hormesis as a Geometric Necessity of Bounded Adaptive Systems: Quantitative Predictions From First Principles.","authors":"Daniel John Murray","doi":"10.1177/15593258261469171","DOIUrl":"10.1177/15593258261469171","url":null,"abstract":"<p><strong>Objectives: </strong>To determine whether hormesis can be derived from the geometry of bounded adaptive biological endpoints, and whether the derivation yields quantitative predictions independent of curve fitting.</p><p><strong>Methods: </strong>Bounded endpoints were represented in rapidity coordinates using the arctanh linearisation of the adopted Möbius composition law. Repair activation and damage accumulation were modelled as opposing bounded rapidity increments with independently measurable thresholds. The molecular-to-functional attenuation factor was derived for linear pathways from the metabolic-control summation theorem and separated from a testable multi-target extension. Predictions were compared with published H₂O₂, CdCl₂, and heat-shock dose-response data.</p><p><strong>Results: </strong>The model predicts a biphasic response whenever repair activation precedes toxicity (D_a < D_t) and high-dose damage ultimately exceeds bounded repair capacity. The exact hyperbolic model is the primary model; the product form is used only as a conservative analytical approximation. Aggregate predictions - peak-amplitude range, mean amplitude, and hormetic-zone width - matched the Calabrese hormesis database of more than 10,000 responses without parameter fitting; across three mechanistically distinct agents, independently published data confirmed the structural prediction that adaptive activation precedes toxicity, and pathway-specific attenuation distinguished linear NRF2-mediated responses (130-160%) from larger multi-target heat-shock responses (200-300%). The peak-location law is presented as a falsifiable prediction.</p><p><strong>Conclusion: </strong>Within the stated scope of independently composing bounded adaptive endpoints, hormesis follows from finite repair capacity plus adaptive upregulation. The framework does not claim that all biological history is axiomatic; it identifies the conditional geometry that constrains dose-response shape once a bounded adaptive endpoint is specified.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"24 3","pages":"15593258261469171"},"PeriodicalIF":2.8,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13392316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148577547","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}