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Silver ion alginate dressing for infection control in type Ⅱ diabetic rats wound: an in vitro and in vivo study 银离子海藻酸盐敷料对Ⅱ型糖尿病大鼠伤口感染控制的体外和体内研究
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-07 DOI: 10.1016/j.jrras.2025.102156
Yao Liang , Shiyuan Xie , Zhongwen Yu , Bin Yang , Jinbin Wei

Background

Diabetic wounds present a formidable therapeutic challenge due to their persistent nature and high complication rates. In this study, the new silver alginate dressing was evaluated to determine whether it improves wound healing in type Ⅱ diabetic rats by comparison with the commercially available silver alginate dressing Biatain® in vivo and in vitro. This study demonstrates that the novel dressing may provide a viable alternative approach to the current management of diabetic wounds.

Methods

The in vitro part involved the evaluation of its water vapor transmission ability, water-uptake ability, and antibacterial ability. Then, Goto-Kakizaki diabetic rats were selected for in vivo experiments to establish the diabetic infection wound model. The healing rate of wounds and the bacterial count on wounds and wound dressings were studied. Detection of fibrinogen (FIB), procalcitonin (PCT), and high-sensitivity C-reactive protein (hs-CRP) by ELISA, Platelet endothelial cell adhesion molecule-1 (CD31) and Alpha-smooth muscle actin (α-SMA) protein expression by histological staining and determination of silver by microwave digestion-inductively coupled plasma mass spectrometry.

Results

In comparison with the commercially available Biatain®, The silver alginate ion dressing has about twice the water absorption capacity of Biatain® (P < 0.01) and On day 14, the wound healing rate in the sample group demonstrated a significant increase of 15.6 % relative to the model group, with wounds approaching near-complete closure.

Conclusion

The newly developed silver-ion alginate dressing enhanced wound closure, reduced infection and healing time, and lowered dressing change frequency, demonstrating comparable efficacy to the commercial reference product (Biatain®) as a practical alternative for diabetic wound care.
背景:糖尿病性伤口由于其顽固性和高并发症发生率,给治疗带来了巨大的挑战。在这项研究中,通过与市售的海藻酸银敷料Biatain®进行体内和体外比较,评估新型海藻酸银敷料是否能促进Ⅱ型糖尿病大鼠的伤口愈合。这项研究表明,这种新型敷料可能为目前糖尿病伤口的治疗提供一种可行的替代方法。方法体外实验对其水蒸气透过能力、吸水能力和抗菌能力进行评价。然后选取Goto-Kakizaki糖尿病大鼠进行体内实验,建立糖尿病感染创面模型。对创面愈合率、创面及敷料细菌计数进行了研究。ELISA法检测纤维蛋白原(FIB)、降钙素原(PCT)、高敏c反应蛋白(hs-CRP),组织学染色法检测血小板内皮细胞粘附分子-1 (CD31)、α-平滑肌肌动蛋白(α-SMA)蛋白表达,微波消解-电感耦合等离子体质谱法检测银含量。结果与市售Biatain®相比,藻酸银离子敷料的吸水量约为Biatain®的两倍(P < 0.01),第14天,样品组创面愈合率较模型组显著提高15.6%,创面接近完全闭合。结论新开发的海藻酸银离子敷料可促进创面愈合,缩短感染和愈合时间,降低换药频率,与商业参考产品(Biatain®)的疗效相当,是糖尿病创面护理的实用替代产品。
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引用次数: 0
A predictive model for functional outcomes in patients with acute anterior circulation stroke based on DWI-ASPECTS and serum homocysteine 基于DWI-ASPECTS和血清同型半胱氨酸的急性前循环卒中患者功能结局预测模型
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-07 DOI: 10.1016/j.jrras.2026.102163
Meilin Wang , Jinsong Cheng

Background

Precise forecasting of functional outcomes is crucial for managing acute anterior circulation stroke (AACS). We sought to develop and validate a predictive model for functional outcomes by integrating the DWI-ASPECTS score and serum homocysteine levels.

Methods

We retrospectively examined information from consecutive AACS patients admitted between January 2022 and January 2025. The individuals were classified into favorable (modified Rankin Scale [mRS] ≤ 2) and unfavorable (mRS >2) outcomes groups depending on their 90-day mRS score. Upon admission, clinical parameters, including the National Institutes of Health Stroke Scale score, were assessed. Diffusion-weighted imaging was performed within 24 h to calculate the DWI-ASPECTS. Blood samples taken from a vein after an overnight fast were gathered within a 24-h timeframe for laboratory testing, including serum homocysteine, glycated hemoglobin, and lipid profiles.

Results

We included 122 patients, among whom 68 cases belonged to the favorable and 54 cases belonged to the unfavorable outcome group. Unfavorable outcome patients were significantly older (P = 0.017), exhibited higher baseline NIHSS scores, lower DWI-ASPECTS scores, and demonstrated elevated serum homocysteine levels (all P < 0.001). Multivariate analysis showed that DWI-ASPECTS score (OR = 0.270, P < 0.001) and serum homocysteine level (OR = 1.539, P < 0.001) independently predicted functional outcome. DWI-ASPECTS (AUC = 0.852) and homocysteine (AUC = 0.844) demonstrated high predictive accuracy. The final nomogram model, which combined these two variables, showed excellent discrimination with an AUC of 0.939 and was well-calibrated.

Conclusion

The developed nomogram, incorporating DWI-ASPECTS and serum homocysteine, demonstrates potential as an effective and accurate method for forecasting functional outcomes in AACS patients, offering a novel approach that integrates neuroanatomical and systemic metabolic information beyond models relying on single parameters.
背景:准确预测功能预后对于急性前循环卒中(AACS)的治疗至关重要。我们试图通过整合DWI-ASPECTS评分和血清同型半胱氨酸水平来开发和验证功能预后的预测模型。方法回顾性分析2022年1月至2025年1月住院的连续AACS患者的信息。根据患者90天mRS评分,将患者分为mRS≤2和mRS≤2两组。入院时,评估临床参数,包括美国国立卫生研究院卒中量表评分。24h内进行弥散加权成像计算DWI-ASPECTS。禁食过夜后采集静脉血样,在24小时内进行实验室检测,包括血清同型半胱氨酸、糖化血红蛋白和脂质谱。结果纳入122例患者,其中良结局组68例,不良结局组54例。不良结局患者明显年龄较大(P = 0.017), NIHSS基线评分较高,DWI-ASPECTS评分较低,血清同型半胱氨酸水平升高(P均为0.001)。多因素分析显示,DWI-ASPECTS评分(OR = 0.270, P < 0.001)和血清同型半胱氨酸水平(OR = 1.539, P < 0.001)独立预测功能结局。DWI-ASPECTS (AUC = 0.852)和同型半胱氨酸(AUC = 0.844)具有较高的预测准确性。结合这两个变量的最终nomogram model具有很好的判别性,AUC为0.939,且校正良好。结论开发的包含DWI-ASPECTS和血清同型半胱氨酸的nomogram预测AACS患者功能结局的方法,提供了一种结合神经解剖学和全身代谢信息的新方法,超越了依赖单一参数的模型。
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引用次数: 0
Dose optimization of stereotactic radiosurgery by 18F-FHBG PET/CT tracking of HSV-TK gene vectors in recurrent glioblastoma: A prospective controlled study 通过18F-FHBG PET/CT追踪复发性胶质母细胞瘤中HSV-TK基因载体的立体定向放射手术剂量优化:一项前瞻性对照研究
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-07 DOI: 10.1016/j.jrras.2025.102127
Jing Ye , Wenbo Cai , Fobao Huang , Xi zhen Xu

Objective

To test whether 18F-FHBG PET tracking of HSV-TK gene-vector expression can guide stereotactic radiosurgery (SRS) dose escalation to improve outcomes versus MRI-only SRS.

Methods

In a single-centre, open-label, randomized phase II trial, 90 patients with recurrent glioblastoma were assigned (1:1) to PET-guided biological target volume SRS (PET-BTV) or standard single-fraction SRS (S-SRS). Primary endpoint was 6-month progression-free survival (PFS6); key secondary endpoints included local control, 12-month overall survival (OS12), ≥grade-3 toxicity, neurocognition (Trail-Making Test-B), and PET reproducibility. PET test–retest reliability and inter-observer agreement were assessed. Time-to-event outcomes used Kaplan–Meier/Cox models; toxicity used Firth logistic regression; repeated measures used appropriate ANOVA.

Results

PET metrics (SUVmax, SUVmean, MTV) showed excellent test–retest reliability (intraclass correlation coefficients >0.85) and robust contouring agreement. Versus S-SRS, PET-BTV improved PFS (hazard ratio [HR] ≈ 0.54) and local control (HR ≈ 0.48; both P < 0.05), with no significant differences in OS12 (HR ≈ 0.71) or ≥ grade-3 toxicity (HR ≈ 0.43; both P > 0.05). Multivariable Cox confirmed treatment group (HR ≈ 0.55), smaller tumour volume (HR ≈ 1.06 per unit), and higher Karnofsky score (HR ≈ 0.97) as independent predictors of longer PFS. PET response (decrease in SUVmax) correlated inversely with risk of progression. Trail-B favored PET-BTV (significant group effect and interaction), suggesting preserved neurocognition.

Conclusions

18F-FHBG PET-guided intratumoral dose painting is feasible, reproducible, and improves PFS and local control without increasing high-grade toxicity, supporting imaging-driven precision re-irradiation for recurrent glioblastoma.
目的探讨18F-FHBG PET对HSV-TK基因载体表达的跟踪是否可以指导立体定向放射手术(SRS)剂量的增加,从而改善预后。方法在一项单中心、开放标签、随机II期试验中,90例复发性胶质母细胞瘤患者按1:1比例被分配到pet引导的生物靶体积SRS (PET-BTV)或标准单组分SRS (S-SRS)。主要终点为6个月无进展生存期(PFS6);关键次要终点包括局部对照、12个月总生存期(OS12)、≥3级毒性、神经认知(Trail-Making Test-B)和PET可重复性。评估PET测试-重测信度和观察者间的一致性。时间-事件结果采用Kaplan-Meier /Cox模型;毒性采用Firth logistic回归;重复测量采用适当的方差分析。结果spet指标(SUVmax、SUVmean、MTV)具有良好的重测信度(类内相关系数>;0.85)和稳健的轮廓一致性。与S-SRS相比,PET-BTV改善了PFS(风险比[HR]≈0.54)和局部对照(HR≈0.48,P < 0.05), OS12 (HR≈0.71)或≥3级毒性(HR≈0.43,P > 0.05)无显著差异。多变量Cox证实治疗组(HR≈0.55)、较小的肿瘤体积(HR≈1.06 /单位)和较高的Karnofsky评分(HR≈0.97)是延长PFS的独立预测因子。PET反应(SUVmax降低)与进展风险呈负相关。Trail-B倾向于PET-BTV(显著的组效应和相互作用),提示神经认知功能得到保护。结论18f - fhbg pet引导下的瘤内剂量显影是可行的、可重复的,在不增加高级别毒性的情况下改善了PFS和局部控制,支持成像驱动的复发性胶质母细胞瘤的精确再照射。
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引用次数: 0
Coptisine suppresses pulmonary nodule carcinogenesis by inducing CAFs mitochondrial apoptosis via Sirt3/YME1L1 黄柏碱通过Sirt3/YME1L1诱导cas线粒体凋亡抑制肺结节癌的发生
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-06 DOI: 10.1016/j.jrras.2025.102148
Jin-Liang Hu , Kun Lv , Jie-Zhong Hu , Zheng Tang , Pia Vanessa C. Basilio
Coptisine, an active alkaloid from Coptis chinensis, exhibits potent anticancer effects by targeting cancer-associated fibroblasts (CAFs) in the tumor microenvironment. This study investigates its mechanism in attenuating lung via Sirt3-mediated deacetylation of YME1L1, regulating mitochondrial apoptosis in CAFs. Orthotopic lung cancer models were established in C57BL/6 mice using SCLC-2 cells, treated with Coptisine (60 or 120 mg/kg/day). In vitro, primary pulmonary fibroblasts (CAFs) co-cultured with SCLC-2 cells were assessed for proliferation (CCK-8), metastasis (Transwell), apoptosis (ELISA), mitochondrial potential (JC-1), and ROS (DCFH-DA). Coptisine inhibited tumor growth, improved lung function, and reduced myofibroblast markers (α-SMA, FAP). It upregulated Bax and Sirt3 while downregulating YME1L1, BCL-2, and EMT proteins (e.g., Vimentin), damaging to mitochondrial function. Mechanistically, Coptisine activated Sirt3 to deacetylate YME1L1, inducing mitochondrial fragmentation in CAFs. These findings highlight Coptisine's potential as a lung cancer therapy by targeting the Sirt3/YME1L1 pathway in CAFs.
黄连碱是黄连中的一种活性生物碱,它通过靶向肿瘤微环境中的癌症相关成纤维细胞(CAFs)而显示出强大的抗癌作用。本研究探讨其通过sirt3介导的YME1L1去乙酰化,调节CAFs线粒体凋亡,从而减轻肺损伤的机制。用SCLC-2细胞在C57BL/6小鼠中建立原位肺癌模型,黄柏碱(60或120 mg/kg/d)处理。在体外,对与SCLC-2细胞共培养的原代肺成纤维细胞(CAFs)的增殖(CCK-8)、转移(Transwell)、凋亡(ELISA)、线粒体电位(JC-1)和ROS (DCFH-DA)进行评估。黄柏碱抑制肿瘤生长,改善肺功能,降低肌成纤维细胞标志物(α-SMA, FAP)。它上调Bax和Sirt3,下调YME1L1、BCL-2和EMT蛋白(如Vimentin),损害线粒体功能。在机制上,黄连碱激活Sirt3使YME1L1去乙酰化,诱导cas线粒体断裂。这些发现强调了Coptisine通过靶向cas中的Sirt3/YME1L1通路作为肺癌治疗的潜力。
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引用次数: 0
Sound-based navigation system for visually impaired individuals 视障人士的声音导航系统
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-05 DOI: 10.1016/j.jrras.2026.102160
Emad Malaekah , Othman Alfahad , Mohsen Bakouri , Adel Gadallah , Suvad Selman , Ahmed Al Rashdi , Husham Saied
Millions of people worldwide have impaired vision for various reasons, such as cataracts, glaucoma, AMD, diabetic retinopathy, trauma, infections, genetic disorders, and amblyopia. Visual impairment ranges from normal vision to complete blindness, with varying severities that affect daily life. This study presents a sound-based navigation system to improve indoor mobility for visually impaired individuals. The system combines voice recognition, LED-guided floor paths, and real-time haptic feedback to help users follow predefined routes. Users issue voice commands to activate illuminated floor strips, which a robot cart follows using light-dependent resistor (LDR) sensors. An electromechanical compass provides accurate orientation, while a vibrating handle delivers haptic alerts for real-time directional adjustments. Bluetooth Low Energy (BLE) determines the user's location and destination to guide them along the correct route. Experimental results show high accuracy: 91.04 % voice recognition, 4 % navigation error due to sensor noise, and 3 % speed regulation error from electrical fluctuations. The proposed solution is cost-effective and user-friendly, promoting greater independence and safety for visually impaired individuals.
全世界有数百万人因各种原因而视力受损,如白内障、青光眼、黄斑变性、糖尿病性视网膜病变、创伤、感染、遗传疾病和弱视。视力障碍的范围从正常视力到完全失明,影响日常生活的严重程度不一。本研究提出一种以声音为基础的导航系统,以改善视障人士的室内行动能力。该系统结合了语音识别、led引导的地板路径和实时触觉反馈,以帮助用户遵循预定义的路线。用户发出语音命令来激活照明的地板条,机器人手推车使用光依赖电阻(LDR)传感器跟随。机电罗盘提供准确的方向,而振动手柄提供实时方向调整的触觉警报。低功耗蓝牙(BLE)可以确定用户的位置和目的地,引导他们沿着正确的路线前进。实验结果表明,该系统的语音识别精度为91.04%,由传感器噪声引起的导航误差为4%,由电波动引起的调速误差为3%。建议的解决方案具有成本效益和用户友好性,促进视障人士更大的独立性和安全性。
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引用次数: 0
Exploring thermodynamic processes through CFD of free convection of Bingham fluids in innovative hexagonal enclosure (Papanastasiou model) 利用CFD研究Bingham流体在创新六角形壳体(Papanastasiou模型)中自由对流的热力学过程
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-04 DOI: 10.1016/j.jrras.2026.102161
Benhanifia Kada , Mebarki Brahim , Ahmed Remlaoui , Keddar Mohammed , Syed M. Hussain , Hijaz Ahmad , Neissrien Alhubieshi , Assmaa Abd-Elmonem , Bandar M. Fadhl , Basim M. Makhdoum
This research presents a unique enclosure geometry, namely, a hexagonal finned cavity, for the analysis of Bingham–Papanastasiou fluid natural convection, which is examined numerically through COMSOL Multiphysics. The momentum and energy equations that govern the phenomena are solved via the Galerkin approach. The external walls have been assumed to be cold, while the inner wall has been taken as hot. A thorough investigation of the thermo-hydrodynamic flow is carried out considering the nominal value of the Rayleigh number (Ra), the range of plasticity Bn (1–50), and the obstacle lengths L (0.1, 0.4). The findings demonstrate that the rate of heat transfer (Nu) is positively correlated with the buoyancy parameter (Ra) while it is inversely related to the plasticity parameter (Bn), with larger values of the latter resulting in lesser heat transfer. This reduction seems to occur due to lame yield stress at a bigger Bn, damping the fluid flow inside the enclosure. The streamline patterns further confirm this trend, showing a significant weakening of circulation at high plasticity levels, particularly for Bn = 50. The effect of obstacle length can be seen on the streamline and isotherm contours, which may indicate the intermediate fin length (L = 0.2) for Rayleigh Number (Ra) as the best, as it increases vortex creation and supports good circulation in the cavity, thus enhancing the heat transfer performance.
本研究提出了一种独特的封闭几何形状,即六角形翅片腔,用于分析Bingham-Papanastasiou流体自然对流,并通过COMSOL Multiphysics进行了数值研究。控制这些现象的动量和能量方程通过伽辽金方法求解。外墙被假定为冷的,而内墙被假定为热的。考虑瑞利数(Ra)的标称值、塑性范围Bn(1-50)和障碍物长度L(0.1, 0.4),对热流体动力流动进行了深入的研究。结果表明:换热速率Nu与浮力参数Ra成正相关,与塑性参数Bn成负相关,后者值越大换热越小。这种减少似乎是由于较大Bn时的屈服应力减弱,从而抑制了外壳内的流体流动。流线模式进一步证实了这一趋势,表明在高塑性水平下环流明显减弱,特别是Bn = 50时。障碍物长度对流线和等温线的影响可以看出,对于瑞利数(Ra),中间翅片长度(L = 0.2)是最好的,它增加了涡流的产生,支持了腔内良好的循环,从而提高了换热性能。
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引用次数: 0
Artificial intelligence in MRI clinical practice: From historical innovation to emerging trends 人工智能在MRI临床实践中的应用:从历史创新到新兴趋势
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-03 DOI: 10.1016/j.jrras.2026.102158
Shrooq T. Aldahery
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引用次数: 0
A machine learning-based gene signature reveals radiotherapy-induced remodeling of the immune microenvironment in esophageal cancer 一项基于机器学习的基因标记揭示了食管癌中放疗诱导的免疫微环境重塑
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-01 DOI: 10.1016/j.jrras.2025.102129
Xiaoyu He , Zhuo Li , Yao Liu , Junsheng Chen , Zihao Yuan , Lina Huang , Ting Wang

Objective

This study aimed to develop a machine learning-based signature using radiotherapy-responsive genes to characterize immune infiltration dynamics and evaluate drug sensitivity in esophageal cancer (EC) before and after radiotherapy.

Methods

Based on the GSE137867 dataset from GEO, which includes 4 pre-radiotherapy and 4 post-radiotherapy esophageal cancer samples, we identified significantly differentially expressed genes (DEGs) through differential analysis. Gene Ontology (GO) analysis and Gene Set Enrichment Analysis (GSEA) were performed based on the DEGs. Signature genes were screened using Lasso and SVM machine learning algorithms. These signature genes underwent CIBERSORT immune infiltration analysis, ssGSEA, ESTIMATE immune scoring, drug sensitivity analysis, and ceRNA network analysis. To validate the expression profiles of the target genes, we cultured the esophageal cancer OE19 cell line and performed Reverse Transcription Quantitative Real-Time Polymerase Chain Reaction (RT-qPCR).

Results

After identifying 28 DEGs, GO and GSEA analysis revealed that these DEGs were enriched in regulation of memory/regulatory T cell differentiation, chemokine activity and cytokine-cytokine receptor interaction pathways. Through Lasso and SVM, three signature genes were identified: ZDHHC11B, CD46, and PFKFB3. CIBERSORT analysis showed a marked elevation in CD8+ T cells after radiotherapy. Drug sensitivity analysis revealed that CD46 was negatively correlated with cisplatin, positively correlated with sapitinib, while PFKFB3 showed a negative correlation with linsitinib. The ceRNA network included 21 miRNAs, 3 mRNAs, and 18 lncRNAs. Specifically, 21 miRNA-mRNA regulatory pairs and 18 lncRNA-mRNA regulatory pairs were identified. RT-qPCR showed that compared with the control group, ZDHHC11B decreased significantly in the post-radiotherapy group, while CD46 and PFKFB3 increased significantly.

Conclusion

This study comprehensively investigated the immune landscape of EC pre- and post-radiotherapy and analyzed drug sensitivity of these signature genes, thereby elucidating alterations in the immune microenvironment of EC and nominating ZDHHC11, CD46, and PFKFB3 as potential biomarkers for predicting immune status and therapeutic sensitivity.
目的利用放射反应基因建立基于机器学习的特征,表征食管癌放疗前后的免疫浸润动力学和药物敏感性。方法基于GEO的GSE137867数据集,包括4个放疗前和放疗后食管癌样本,通过差异分析鉴定出显著差异表达基因(DEGs)。基于DEGs进行基因本体(GO)分析和基因集富集分析(GSEA)。使用Lasso和SVM机器学习算法筛选特征基因。对这些特征基因进行了CIBERSORT免疫浸润分析、ssGSEA、ESTIMATE免疫评分、药物敏感性分析和ceRNA网络分析。为了验证靶基因的表达谱,我们培养了食管癌OE19细胞系,并进行了逆转录定量实时聚合酶链反应(RT-qPCR)。结果鉴定出28个DEGs后,GO和GSEA分析显示,这些DEGs富集于调节记忆/调节性T细胞分化、趋化因子活性和细胞因子-细胞因子受体相互作用途径。通过Lasso和SVM分别鉴定出ZDHHC11B、CD46和PFKFB3三个特征基因。CIBERSORT分析显示放疗后CD8+ T细胞明显升高。药敏分析显示CD46与顺铂呈负相关,与沙匹替尼呈正相关,而PFKFB3与利西替尼呈负相关。ceRNA网络包括21个mirna, 3个mrna和18个lncrna。具体来说,鉴定了21对miRNA-mRNA调控对和18对lncRNA-mRNA调控对。RT-qPCR结果显示,与对照组相比,放疗后组患者ZDHHC11B水平明显降低,CD46、PFKFB3水平明显升高。结论本研究全面研究了EC放疗前后的免疫景观,分析了这些特征基因的药物敏感性,从而阐明了EC免疫微环境的变化,并提名ZDHHC11、CD46和PFKFB3作为预测免疫状态和治疗敏感性的潜在生物标志物。
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引用次数: 0
Integrated RP-HPLC degradation profiling and Monte Carlo modeling for evaluating gamma-ray radiosterilization suitability of imidazole antifungals 综合RP-HPLC降解谱和蒙特卡罗模型评价咪唑类抗真菌药物的γ射线灭菌适宜性
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-31 DOI: 10.1016/j.jrras.2025.102132
Abdelmoneim Saleh , Zehra Üstün , Ümit Kara
This study introduces an integrated approach combining forced degradation analysis and Monte Carlo gamma modeling to assess the radiosterilization suitability of pharmaceutical compounds. Three imidazole antifungals were subjected to controlled UV (365 nm) and oxidative (3 % H2O2) stress conditions, and their degradation behavior was quantitatively assessed using validated reversed phase high performance liquid chromatography (RP-HPLC), yielding percentage degradation, rate constants, and half-life values. UV degradation after 3h was highest for lanoconazole (70.97 %), followed by bifonazole (50.80 %) and butoconazole (15.44 %), confirming greater photostability for butoconazole. Under oxidative stress, bifonazole showed the highest resistance, while lanoconazole fully degraded within 12h. MCNPX Monte Carlo simulations revealed enhanced gamma attenuation and localized energy deposition for bifonazole, consistent with its experimental degradation resistance. Kerma and dose-rate analyses supported a balanced energy deposition profile for bifonazole, correlating with its experimental stability. The integration of chemical degradation profiling via RP-HPLC with physical interaction modeling via Monte Carlo simulations offers a predictive, quantitative framework for assessing radiosterilization tolerance. This approach reduces reliance on empirical irradiation trials, enables early identification of the most stable active pharmaceutical ingredients, and supports the optimization of sterilization protocols in pharmaceutical development. This framework enables early identification of radiation-stable APIs, minimizing empirical trials and supporting optimized sterilization strategies without compromising drug efficacy.
本研究引入了一种结合强制降解分析和蒙特卡罗伽马模型的综合方法来评估药物化合物的放射性灭菌适用性。在可控紫外(365 nm)和氧化(3% H2O2)胁迫条件下,对3种咪唑类抗真菌药物的降解行为进行了定量评价,并采用反相高效液相色谱法(RP-HPLC)对其降解率、速率常数和半衰期进行了定量评价。紫外降解率最高的是硝康唑(70.97%),其次是联苯唑(50.80%)和丁康唑(15.44%),说明丁康唑具有较好的光稳定性。在氧化应激下,苯苯唑表现出最高的抗性,而硝康唑在12h内完全降解。MCNPX蒙特卡罗模拟显示,联苯唑的伽马衰减和局部能量沉积增强,与实验中抗降解性一致。Kerma和剂量率分析支持了联苯唑的平衡能量沉积谱,这与它的实验稳定性有关。通过RP-HPLC进行的化学降解分析与通过蒙特卡罗模拟进行的物理相互作用建模相结合,为评估放射性灭菌耐受性提供了预测的定量框架。这种方法减少了对经验性辐照试验的依赖,能够早期识别最稳定的活性药物成分,并支持药物开发中灭菌方案的优化。该框架能够早期识别辐射稳定的原料药,最大限度地减少经验性试验,并在不影响药物功效的情况下支持优化的灭菌策略。
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引用次数: 0
Network pharmacology, molecular dynamics simulation, and experiments uncover icariin's role in ferroptosis during postmenopausal osteoporosis 网络药理学,分子动力学模拟和实验揭示淫羊藿苷在绝经后骨质疏松症中铁下垂的作用
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-31 DOI: 10.1016/j.jrras.2025.102147
Feng Chen , Yueping Chen , Xiaoyun Zhang

Background

Icariin (ICA) shows therapeutic potential for postmenopausal osteoporosis (PMO), yet its mechanism in regulating osteoblast ferroptosis remains unclear. We combined network pharmacology, molecular docking, molecular dynamics simulation, and in vitro validation to elucidate ICA-mediated anti-ferroptotic effects in PMO.

Methods

Potential ICA targets were obtained from PubChem, the Comparative Toxicogenomics Database, SwissTargetPrediction, and the Similarity Ensemble Approach, while PMO-associated genes were identified through GeneCards, OMIM, DrugBank, and the Therapeutic Target Database. Ferroptosis-related genes were extracted from FerrDb. Intersecting targets were used to construct drug–target and protein–protein interaction (PPI) networks, and key nodes were identified by topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to perform functional enrichment. Molecular docking assessed ICA affinity toward candidate proteins, and molecular dynamics simulations evaluated complex stability. Reactive oxygen species (ROS), apoptosis, and the expression of markers linked to ferroptosis, antioxidants, and osteogenesis were measured using osteoblasts in vitro using quantitative RT-PCR and western blotting.

Results

Eight key targets were identified through PPI network analysis. GO and KEGG enrichment analyses highlighted pathways associated with redox regulation and ferroptosis. Docking studies revealed the strongest binding affinity between ICA and Nrf2 (Nuclear Factor Erythroid 2–Related Factor 2), further confirmed by stable interactions in molecular dynamics simulations. Experimentally, ICA promoted osteoblast proliferation, reduced intracellular ROS levels and apoptosis, and upregulated antioxidant, osteogenic, and ferroptosis-related proteins, including Nrf2, heme oxygenase-1 (HO-1), glutathione peroxidase-4 (GPX4), solute carrier family 7 member 11 (SLC7A11), alkaline phosphatase (ALP), and runt-related transcription factor-2 (RUNX2), while suppressing caspase-3 activation.

Conclusion

ICA activates the Nrf2/HO-1 pathway to suppress ferroptosis and oxidative stress, reduce apoptosis, and promote osteogenic activity, thereby alleviating PMO-related osteoblast dysfunction. These findings provide mechanistic support for ICA as a multi-target candidate for PMO management.
背景:dicariin (ICA)显示出治疗绝经后骨质疏松症(PMO)的潜力,但其调节成骨细胞铁下垂的机制尚不清楚。我们结合网络药理学、分子对接、分子动力学模拟和体外验证等方法,阐明了ica介导的PMO抗铁衰作用。方法通过PubChem、Comparative Toxicogenomics Database、SwissTargetPrediction和Similarity Ensemble Approach获得潜在的ICA靶点,通过GeneCards、OMIM、DrugBank和Therapeutic Target Database鉴定pmo相关基因。从ferdb中提取了嗜铁相关基因。利用交叉靶点构建药物-靶点-蛋白相互作用(PPI)网络,通过拓扑分析确定关键节点。使用基因本体(GO)和京都基因与基因组百科全书(KEGG)分析进行功能富集。分子对接评估了ICA对候选蛋白的亲和力,分子动力学模拟评估了复合物的稳定性。利用体外成骨细胞,采用定量RT-PCR和western blotting技术,测量了活性氧(ROS)、细胞凋亡以及与铁凋亡、抗氧化剂和成骨相关的标志物的表达。结果通过PPI网络分析,确定了8个关键靶点。GO和KEGG富集分析强调了与氧化还原调节和铁下垂相关的途径。对接研究发现ICA与Nrf2 (Nuclear Factor Erythroid 2 - related Factor 2)的结合亲和性最强,分子动力学模拟进一步证实了这一点。实验结果表明,ICA可促进成骨细胞增殖,降低细胞内ROS水平和细胞凋亡,上调抗氧化、成骨和凋亡相关蛋白,包括Nrf2、血红素加氧酶-1 (HO-1)、谷胱甘肽过氧化物酶-4 (GPX4)、溶质载体家族7成员11 (SLC7A11)、碱性磷酸酶(ALP)和矮子相关转录因子-2 (RUNX2),同时抑制caspase-3的激活。结论ica激活Nrf2/HO-1通路,抑制铁凋亡和氧化应激,减少细胞凋亡,促进成骨活性,从而减轻pmo相关成骨细胞功能障碍。这些发现为ICA作为PMO管理的多靶点候选提供了机制支持。
{"title":"Network pharmacology, molecular dynamics simulation, and experiments uncover icariin's role in ferroptosis during postmenopausal osteoporosis","authors":"Feng Chen ,&nbsp;Yueping Chen ,&nbsp;Xiaoyun Zhang","doi":"10.1016/j.jrras.2025.102147","DOIUrl":"10.1016/j.jrras.2025.102147","url":null,"abstract":"<div><h3>Background</h3><div>Icariin (ICA) shows therapeutic potential for postmenopausal osteoporosis (PMO), yet its mechanism in regulating osteoblast ferroptosis remains unclear. We combined network pharmacology, molecular docking, molecular dynamics simulation, and in vitro validation to elucidate ICA-mediated anti-ferroptotic effects in PMO.</div></div><div><h3>Methods</h3><div>Potential ICA targets were obtained from PubChem, the Comparative Toxicogenomics Database, SwissTargetPrediction, and the Similarity Ensemble Approach, while PMO-associated genes were identified through GeneCards, OMIM, DrugBank, and the Therapeutic Target Database. Ferroptosis-related genes were extracted from FerrDb. Intersecting targets were used to construct drug–target and protein–protein interaction (PPI) networks, and key nodes were identified by topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to perform functional enrichment. Molecular docking assessed ICA affinity toward candidate proteins, and molecular dynamics simulations evaluated complex stability. Reactive oxygen species (ROS), apoptosis, and the expression of markers linked to ferroptosis, antioxidants, and osteogenesis were measured using osteoblasts in vitro using quantitative RT-PCR and western blotting.</div></div><div><h3>Results</h3><div>Eight key targets were identified through PPI network analysis. GO and KEGG enrichment analyses highlighted pathways associated with redox regulation and ferroptosis. Docking studies revealed the strongest binding affinity between ICA and Nrf2 (Nuclear Factor Erythroid 2–Related Factor 2), further confirmed by stable interactions in molecular dynamics simulations. Experimentally, ICA promoted osteoblast proliferation, reduced intracellular ROS levels and apoptosis, and upregulated antioxidant, osteogenic, and ferroptosis-related proteins, including Nrf2, heme oxygenase-1 (HO-1), glutathione peroxidase-4 (GPX4), solute carrier family 7 member 11 (SLC7A11), alkaline phosphatase (ALP), and runt-related transcription factor-2 (RUNX2), while suppressing caspase-3 activation.</div></div><div><h3>Conclusion</h3><div>ICA activates the Nrf2/HO-1 pathway to suppress ferroptosis and oxidative stress, reduce apoptosis, and promote osteogenic activity, thereby alleviating PMO-related osteoblast dysfunction. These findings provide mechanistic support for ICA as a multi-target candidate for PMO management.</div></div>","PeriodicalId":16920,"journal":{"name":"Journal of Radiation Research and Applied Sciences","volume":"19 1","pages":"Article 102147"},"PeriodicalIF":2.5,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145880591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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Journal of Radiation Research and Applied Sciences
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