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关键词： ENN   ESM-2 model   IL-4 inducing peptides   Protein language model   SMOTE  

摘要： Despite progress in developing antiviral drugs and vaccines, infections continue to be a significant challenge. Interleukin-4 (IL-4) is crucial for regulating immune responses and mediating allergic reactions. This research aims to improve the predictive accuracy of IL-4-inducing peptides by tackling data imbalance and enhancing feature extraction. Specifically, we introduce a new approach that utilizes SMOTE and ENN for balancing the dataset and applies a 30-layer ESM-2 model for extracting deep features. The extracted features are subsequently processed through a Gated Recurrent Unit (GRU) model, which is optimized through hyperparameter tuning. Our method achieves notable improvements, with an AUC of 0.98 and an accuracy of 93.1 %, highlighting its potential to support future immunotherapy and vaccine development efforts. The PLM-IL4 web server is freely accessible at http://***/PLM-IL4, and the datasets used in this research are also available for download from the website. © 2025 Elsevier Ltd

关键词： 骨细胞   骨衰老   免疫微环境   免疫细胞   细胞因子   免疫衰老   免疫治疗   工程化组织构建  

摘要： 背景:骨骼微环境中富含各种免疫细胞和细胞因子,它们与骨细胞紧密联系形成了相互影响的网络,因此,骨骼的衰老不单单是由骨细胞衰老导致,免疫系统衰老同样会加速骨衰老过程。目的:综述骨髓间充质干细胞、成骨细胞和破骨细胞以及骨微环境中免疫细胞的年龄相关变化,强调免疫微环境在骨衰老中的关键作用以及免疫治疗在骨衰老治疗中的潜力。方法:检索PubMed数据库、中国知网中关于骨骼细胞衰老与免疫细胞衰老相互作用的文献,英文检索词为“Osteocytes,Bone aging,Immune microenvironment,Immune cells,Cytokines,Immunosenescence,Immunotherapy”,中文检索词为“骨细胞,骨衰老,免疫微环境,免疫细胞,细胞因子,免疫衰老,免疫治疗”。根据纳入与排除标准,最终纳入128篇文献进行综述。结果与结论:骨衰老是老年人普遍存在的一种病理状态,以多种生物学过程相互作用为特征,其中免疫因素起着关键作用。免疫微环境中的细胞、分子和信号通路共同构成了一个复杂的网络,这个网络的失衡会加速骨衰老进程。抗细胞衰老与免疫治疗相结合可能为骨衰老疾病的治疗带来新的方法,包括清除衰老的细胞、衰老相关分泌表型靶向药物、炎症细胞因子靶向治疗、免疫细胞调节疗法、干细胞治疗及分子治疗等。为了更有效且合理地清除衰老细胞,需要更深入地了解衰老细胞的机制,这将有助于更准确地识别衰老细胞。免疫治疗在骨衰老治疗中展现出强大的潜力和前途,但存在一些潜在的风险。相信随着科技的进步,人们可以更准确地了解人体的遗传信息和免疫状态,制定更个性化的免疫治疗方案。

关键词： 天然产物   细胞焦亡   炎性小体   炎症   脊髓损伤   继发性损伤   神经功能   经典途径  

摘要： 背景:神经炎症是脊髓损伤后病情加重的主要原因。近年来,细胞焦亡因显著的促炎特征而受到广泛关注。部分天然产物通过调控脊髓损伤后的细胞焦亡水平,能显著抑制炎症反应,改善受损的神经功能,为脊髓损伤提供了新的治疗思路。目的:总结天然产物调控细胞焦亡治疗脊髓损伤的作用机制,以期为今后脊髓损伤的治疗研究提供借鉴和参考。方法:以“spinal cord injury,pyroptosis,inflammasome,natural products,natural compounds,Traditional Chinese Medicine”“脊髓损伤,细胞焦亡,炎性小体,天然产物,天然化合物,中药”为检索词,在PubMed、Web of Science、万方、中国知网检索自建库以来至2024年9月的有关文献,按照纳入和排除标准,最终得到75篇相关文献。结果与结论:①细胞焦亡是脊髓损伤的重要促炎途径,控制细胞焦亡是改善受损神经功能的有效方式;②部分天然产物可以通过NLRP3/Caspase-1经典焦亡途径、核因子κB相关通路、Nrf2/HO-1等其他上游通路和自噬来调控细胞焦亡,从而影响脊髓损伤后的组织炎症水平,加快神经功能恢复;③这些天然产物的抗细胞焦亡作用多依赖于NLRP3经典焦亡途径,尚缺少关于其他焦亡途径的研究;④该领域仍存在很多问题,如这些天然产物目前没有相应的临床研究证据支持;⑤天然产物在调控细胞焦亡中具有巨大的潜能,有望成为治疗脊髓损伤的有力武器。

关键词： 创伤性脑损伤   骨痂   骨折愈合   炎症反应   细胞因子   激素   神经肽   基因   干细胞  

摘要： 背景:骨折延迟愈合和不愈合是常见的临床问题。在临床观察中,常见到合并创伤性脑损伤的四肢骨折患者的骨折愈合速度明显快于无脑损伤的患者。这一现象背后的可能机制已成为当前研究的重要焦点。近年来的研究表明,创伤性脑损伤通过调控细胞因子、激素、神经信号以及干细胞等机制,显著加速了骨痂形成和骨折愈合过程。目的:总结创伤性脑损伤促进骨痂形成及骨折愈合机制的最新研究进展,为临床应用提供理论依据。方法:文章第一作者通过检索中国知网、万方、维普、PubMed、Embase、Web of Science及Cochrane Library数据库2013年1月至2024年10月相关文献,个别文献追溯至20年前。检索词为“创伤性脑损伤,骨痂,骨折愈合,炎症反应,细胞因子,激素,神经肽,基因,干细胞”“traumatic brain injury,callus,fracture healing,inflammatory response,cytokines,hormones,neuropeptides,genes,stem cells”,最终选取符合纳入标准的文献共计83篇。结果与结论:创伤性脑损伤对骨痂形成及骨折愈合的促进作用机制极其复杂,涉及细胞因子、激素、神经系统和干细胞等多个调节环节。然而,目前关于创伤性脑损伤促进骨痂形成及骨折愈合的具体机制尚未得到全面、清晰的理解,仍需进一步深入研究。现有研究表明,创伤性脑损伤主要通过促进细胞因子(如胰岛素样生长因子1)和激素(如生长激素及瘦素)的释放,调控神经系统,促进干细胞的增殖与分化等机制来加速骨痂形成和骨组织再生。此外,创伤性脑损伤会引发一系列免疫反应,包括炎症因子的释放和免疫细胞的激活,这些反应能够调节骨折修复的过程。具体而言,免疫反应通过增强局部血流、促进细胞迁移和激活成纤维细胞,从而支持骨愈合的不同阶段。同时,创伤性脑损伤诱发的干细胞活化也在骨折修复中发挥了关键作用。活化的干细胞能够分化为骨细胞、软骨细胞和脂肪细胞,促进骨组织再生和修复。因此,创伤性脑损伤诱发的免疫反应与干细胞的活化共同作用,为骨折愈合提供了必要的支持。这些机制能够加速骨愈合过程,显著缩短愈合时间,提升骨折患者的预后。综上所述,创伤性脑损伤通过多重机制促进骨痂形成和骨折愈合,展现其在骨修复中的重要性。未来研究应聚焦创伤性脑损伤影响骨愈合的信号通路及调控因子,深入理解其作用机制,这将为开发靶向治疗、干细胞及神经调控疗法提供理论基础,具有缩短愈合时间、优化康复方案、改善预后的临床价值。因此,探索创伤性脑损伤引发的生物效应将为骨折治疗开辟新途径。

关键词： 干细胞   卵巢颗粒细胞   衰老   机制   氧化应激   抑制凋亡   细胞因子   抗氧化   抗炎症反应  

摘要： 背景:干细胞疗法作为一种新兴的治疗手段,有望改善卵巢环境,延缓卵巢颗粒细胞的衰老,为高龄妊娠女性带来新的希望。目的:综述干细胞抗卵巢颗粒细胞衰老的机制及研究进展。方法:检索中国知网和PubMed数据库中关于干细胞抗卵巢颗粒细胞衰老的文献,以“干细胞,卵巢颗粒细胞,衰老”为中文检索词,以“stem cells,ovary granulosa cells,aging”为英文检索词,最终纳入67篇文献进行分析。结果与结论:①总结了5种卵巢颗粒细胞衰老的机制:DNA损伤和修复能力下降、氧化应激、线粒体功能受损、炎症反应、激素水平变化;②整理了当前干细胞治疗卵巢颗粒细胞衰老的5种机制:促进增殖和抑制凋亡、分化潜能及再生能力、分泌因子、抗氧化、抗炎症反应和免疫调节;③目前有多种类型的干细胞可通过多种方式协同治疗卵巢颗粒细胞衰老,干细胞疗法在恢复女性生育能力方面具有广阔前景。

关键词： IL-23   IL-17   bioinformatics   cytokine   gene   inflammation   receptor  

摘要： Introduction/Objective Bioinformatic analysis is a valuable tool that allows us to collect, archive, analyze, and disseminate biological data for further interpretation. Analysis of the IL-23/IL-17A axis and its receptors will provide us with essential information about their functions, interactions, and relationships with various diseases. This review aims to identify the central genes co-expressed in the IL-23/IL-17A axis and their receptors and to understand their ontology and modifying *** We used several databases, including COXPRESdb to obtain the co-expressed genes, ShinyGO and ToppGene platforms to explore gene functional enrichment, and the NetworkAnalyst 3.0 platform for gene expression *** We found that genes encoding IL-23/IL-17A axis proteins and their receptors mainly respond to microbial components, participate in the inflammatory response, and are primarily associated with inflammatory and autoimmune diseases. In addition, we observed an association of the IL-23/IL-17 axis with Behcet's disease, Graft-versus-host disease, and Hodgkin's disease, although there is no direct evidence of their *** The IL-23/IL-17A axis is associated with several inflammatory and autoimmune pathologies. Therefore, we suggest further research to confirm its role in these pathologies and, if possible, use it as a therapeutic target.

关键词： Inflammatory signaling   oxidative stress signaling   immune signaling   myocardial cell injury   elderly  

摘要： Introduction The mutual activations of multiple signaling pathways are the key factors in the development and progression of myocardial cell injuries. Objective This research aimed to compare the different degrees of myocardial injury after coronary stenting, permanent pacemaker implantations, or cardiac radiofrequency ablation and to investigate the effects of the mutual activation of TNF-alpha/NF-kappa B, TLR2/TLR4, and ROS/MDA signaling pathways on myocardial injury in elderly patients after coronary stents or permanent pacemakers or radiofrequency ablation. Methods We determined reactive oxygen species (ROS), malondialdehyde (MDA), toll-like receptor 2 (TLR2), toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-kappa B), tumor necrosis factor-alpha (TNF-alpha) and high-sensitive cardiac troponin T (hs-cTnT) as a marker of myocardial injury in patients. Results The levels of ROS, MDA, TLR2, TLR4, NF-kappa B, TNF-alpha, and hs-cTnT were increased in patients with permanent pacemaker implantations when compared to patients with cardiac radiofrequency ablation (P < 0.01) at 6 months and were further increased in patients with coronary stenting compared to patients with cardiac radiofrequency ablation and permanent pacemaker implantations at 6 months, respectively (P < 0.01). This research confirmed that ROS, MDA, TLR2, TLR4, NF-kappa B, and TNF-alpha predicted myocardial injury severity. Conclusion Oxidative stress (ROS/MDA signaling pathway) may be linked to immune response (TLR2/TLR4 signaling pathway) and pro-inflammatory response (TNF-alpha/NF-kappa B signaling pathway) in myocardial injury, and ROS/MDA signaling may play a dominant role.

关键词： Colorectal cancer   Immunotherapy resistance   CD8+T cells   IL32   Nano-selenium   Engineered probiotics   Extracellular vesicles   Tumor microenvironment   Biomaterial therapy  

摘要： Background and objective: Colorectal cancer (CRC) is a major global health burden, with immunotherapy often limited by immune tolerance and resistance. This study introduces an innovative approach using Selenium Nanoparticles-Loaded Extracellular Vesicles combined with Interleukin-32 and Engineered Probiotic Escherichia coli Nissle 1917 (SeNVs@NE-IL32-EcN) to enhance CD8+ T cell-mediated immune responses and overcome immunotherapy resistance. Methods: Single-cell RNA sequencing (scRNA-seq) and transcriptomic analyses were performed to identify key immune cells and regulators involved in CRC immunotherapy resistance, focusing on CD8+ T cells and the regulatory factor IL32. A humanized xenograft mouse model was used to evaluate the impact of IL32 and SeNVs@NE-IL32-EcN on tumor growth and immune responses. The SeNVs@NE-IL32-EcN complex was synthesized through a reverse micelle method and functionalized using extracellular vesicles. Its morphology, size, antioxidant activity, and safety were characterized using electron microscopy, dynamic light scattering (DLS), and in vitro co-culture assays. Results: Single-cell analyses revealed a significant reduction in CD8+ T cell infiltration in immunotherapyresistant CRC patients. IL32 was identified as a key regulator enhancing CD8+ T cell cytotoxic activity through granzyme B and IFN-gamma secretion. Treatment with SeNVs@NE-IL32-EcN significantly improved the proliferation and activity of CD8+ T cells and reduced tumor progression in humanized mouse models. In vitro and in vivo results demonstrated the complex's biocompatibility, antioxidant properties, and ability to enhance CRC immunotherapy while mitigating immune tolerance. Conclusion: SeNVs@NE-IL32-EcN offers a novel nano-biomaterial strategy that integrates nanotechnology and probiotic therapy to enhance CD8+ T cell-mediated immunity and overcome CRC immunotherapy resistance. This study lays the foundation for future therapeutic applications in cancer treatment by advan

关键词： 异基因造血干细胞移植   新鲜脐血移植   β重型地中海贫血   移植物抗宿主病   儿童  

摘要： 背景:异基因造血干细胞移植是目前根治重型地中海贫血最有效的方法,然而仅有不到一半的患者能找到相合的骨髓或外周血干细胞。同胞来源脐血干细胞与骨髓和外周血干细胞具有不同的特征,是重型地中海贫血患者移植治疗的一种潜在造血干细胞替代来源。目的:探讨应用人类白细胞抗原相合同胞新鲜脐血移植治疗儿童β重型地中海贫血的疗效。方法:选择2010年6月至2020年6月南方医科大学南方医院收治的β重型地中海贫血患儿48例,男28例,女20例,中位年龄4岁,均接受人类白细胞抗原相合同胞新鲜脐血移植治疗,脐血移植前均采用清髓性不含抗胸腺细胞球蛋白的预处理方案,脐血移植后均采用环孢素A+吗替麦考酚酯+/-短程甲氨蝶呤预防移植物抗宿主病。结果与结论:(1)48例患儿输注的总有核细胞中位数为8.17×10^(7)/kg,输注的CD34^(+)细胞中位数为2.40×10^(5)/kg,脐血移植后中位随访时间98个月,44例植入成功,粒细胞和血小板植入中位时间分别为28 d和31 d,其中37例移植后植入证据检测为供者型完全嵌合,7例移植后早期检测为供受者稳定混合嵌合;(2)44例植入成功患儿中,4例发生急性移植物抗宿主病,分别为Ⅰ级(n=2)和Ⅱ级(n=2),受累器官均为皮肤,均未发生慢性移植物抗宿主病;(3)脐血移植后,48例患儿中5例发生巨细胞病毒感染及激活,12例发生败血症,3例发生侵袭性真菌病,21例发生口腔炎,8例发生出血性膀胱炎,1例发生肝静脉闭塞;(4)48例患儿中,47例存活,1例在移植后28 d因重症肺炎合并急性心力衰竭死亡,43例无病存活,3例发生原发性植入失败,1例发生移植后全血细胞减少,5年总生存率和无病生存率分别为98%和89%,1年时移植相关死亡的累计发病率为2.1%;(5)结果显示,人类白细胞抗原相合同胞新鲜脐血移植治疗儿童β重型地中海贫血的效果良好,移植物抗宿主病的发生风险低。

关键词： Acetamiprid   Biochemical/molecular analysis   Eruca vesicaria essential oil   GC-MS analysis   Nephrotoxicity   Oxidative stress  

摘要： Acetamiprid (Aceta) is a neonicotinoid insecticide utilized extensively worldwide, and its environmental and human health risks are of concern. Eruca vesicaria is an edible year-round plant that contains a lot of health-promoting phytochemicals and is an excellent source of antioxidants. So, the present investigation was planned to assess the effect of E. vesicaria seed essential oil versus acetamiprid-induced toxicity in rats. Animals were partitioned into 4 groups of seven each: control, E. vesicaria seeds essential oil (ESEO;0.17 mL/kg), acetamiprid (Aceta;21.7 mg/kg), and ESEO plus Aceta, respectively. Doses were given orally and daily for 14 days. Results revealed that ESEO has many phytochemical components with high antioxidant activity. Data showed that treatment with Aceta increased lipid peroxidation and decreased the activities of “enzymatic and non-enzymatic antioxidants” in kidney homogenate. Also, disturbance of kidney and liver function biomarkers, lipid profile, and protein content were observed. These are confirmed by the histological, molecular (Cox-2, TNF-α, and PPAR-α), and renal damage biomarkers (KIM-1 and Cystatin C) examination. On the other hand, rats administered ESEO and then treated with Aceta showed significant amelioration in most of the examined indices. To sum up, ESEO has a potent anti-inflammatory, anti-apoptotic, and antioxidant activity that protects against the pronounced harmful effects of Aceta in rat kidneys due to its health-promoting phytochemicals. © 2025 Elsevier Ltd