Cellular Senescence and SENEX Gene on the Peripheral CD4+CD25+ Treg Cells Enhancement in Elderly

Cellular senescence is a signal transduction process which maintained genomic stability and stopped mammalian cell growth. Furthermore, cellular senescence induces a protective response to a variety of DNA damage. However, this process is also associated with apoptosis, upregulated secretion of inflammatory cytokine, and promoted surrounding tissue damage. When cellular senescence accumulates to a certain extent, it triggers geriatric diseases, such as chronic inflammation, immune senescence-associated tumors and incontrollable infections. Cellular senescence gene SENEX, which was cloned in 2004, has been demonstrated to play a unique gatekeeper function in human endothelial cells when stress-induced pre-mature senescence and apoptosis occurr. The phenomenon that CD4+CD25+ Treg cells accumulated in the aged population has been well studied in recent years. Now Treg accumulation related to immune-pathology has attracted more interest. CD4+CD25+ Treg did not decline and age, but accumulated and suppressed immunoreaction. The enhanced Treg number and function may be associated with stress-induced premature senescence-mediated unique cellular senescence protection mechanisms, and SENEX may play a critical role in this process. In this article, we summarize the cellular senescence and SENEX gene in the accumulation and functional activity of CD4+CD25+ Treg in the elderly.

Direct Correlation among Telomere Length, Cellular Aging, and Rejuvenation Effects of Honey Child Powder

Purpose: Telomere length (TL) is an indicator of age;however, hormonal influences complicate individual aging. It remains unclear whether TL shortening is a direct factor in both individual and cellular aging. Therefore, we examined the direct relationship between TL and cellular senescence at the cellular level. Methods: Telomerase activity, TL, and gene expression were measured in cultured human lung-, fetal-, and skin-derived fibroblasts, human skin keratinocytes, and telomerase reverse transcriptase (TERT) gene-immortalized cells using detection kits, Cawthon’s method, and reverse transcription-quantitative polymerase chain reaction, respectively. Novel substances that elongate telomeres were screened to confirm cell rejuvenation effects. Results: Long-term cell culture of TIG-1-20 normal human fibroblasts resulted in TL shortening, decreased division rate, and senescence progression, whereas in OUMS-36T-2 cells, TL elongation via TERT gene transfer increased the division rate, reduced endoplasmic reticulum stress, and upregulated genes associated with young individuals, indicating that cellular rejuvenation occurs via TL elongation. In addition, a honey child powder (HCP) extract was found through screening, and the HCP extract strongly suppressed the menin gene, resulting in increased telomerase activity and extended cell lifespan. Upon addition of the HCP extract to skin fibroblasts, gene expression of moisturizing components, including collagen, hyaluronic acid, and elastin, increased, and exhibited a rejuvenating effect with an increase in elastin amount. Conclusions: TL elongation or shortening is involved in cell proliferation rate and cellular aging, and TL elongation rejuvenates cells. In addition, HCP extract has a rejuvenating effect on cells and is expected to be a rejuvenating compound.

Gold Standard for Skin Cancer Treatment: Surgery (Mohs) or Microscopic Molecular-Cellular Therapy (Curaderm)?

Non-melanoma skin cancers or keratinocyte cancers such as basal cell carcinoma and squamous cell carcinoma make up approximately 80% and 20% respectively, of skin cancers with the 6 million people that are treated annually in the United States. 1 in 5 Americans and 2 in 3 Australians develop skin cancer by the age of 70 years and in Australia it is the most expensive, amassing $1.5 billion, to treat cancers. Non-melanoma skin cancers are often self-detected and are usually removed by various means in doctors’ surgeries. Mohs micrographic surgery is acclaimed to be the gold standard for the treatment of skin cancer. However, a novel microscopic molecular-cellular non-invasive topical therapy described in this article, challenges the status of Mohs procedure for being the acclaimed gold standard.

细胞自噬在脑缺血损伤中的作用及中药调控机制

背景:研究表明缺血诱发的细胞自噬失调是脑损伤的关键因素,自噬相关基因6、微管相关蛋白轻链3、p62等自噬关键蛋白参与神经元轴突变性、死亡、细胞内稳态维持等过程,对神经功能的恢复起重要作用。目的:综述细胞自噬在脑缺血损伤中的作用及中药调控机制的研究进展。方法:第一作者以“缺血性中风,脑组织损伤,细胞自噬,信号通路,中药,复方,萜类,生物碱,黄酮,皂苷,木脂素,苯酞类等”为中文检索词,以“Ischemic stroke,brain tissue damage,cellular autophagy,signaling pathways,traditional Chinese medicine,compounds,terpenoids,alkaloids,flavonoids,saponins,lignans,phthalates”为英文检索词,检索2016年1月至2024年2月中国知网和PubMed数据库中有关细胞自噬在脑缺血损伤中的作用及中药调控机制的文献,排除与文章相关性不高、重复及过时的文献。共检索出1746篇相关文献,最终纳入92篇文献进行综述。结果与结论:大量文献研究证实,细胞自噬在脑缺血损伤中具有重要作用,适度的自噬可促进细胞存活,过度自噬则加重脑损伤;而中药可在脑缺血的不同时期,通过调节PI3K/Akt/mTOR、AMPK-mTOR及丝裂原激活蛋白激酶等信号通路,调节自噬相关蛋白表达,抑制神经元坏死、凋亡,发挥神经保护作用。

金属成形过程组织演变的Cellular Automaton模拟技术

结合金属凝固过程和热成形过程的温度场、浓度场、应力应变场等的数值模拟和金属结晶、再结晶过程中的热力学、动力学条件，建立了金属成形过程组织演变的宏－微观耦合模型．利用ＣｅｌｌｕｌａｒＡｕｔｏｍａｔｏｎ方法，依据建立的模型对Ｋ４１７Ｎｉ基合金叶片的凝固组织形成过程和热加工过程的再结晶组织进行了模拟．

基于热力学函数的纳米晶粒长大Cellular Automaton仿真研究

基于纳米晶热力学特性表征函数,将纳米晶热力学性质对晶界迁移的影响引入Cellular Automaton算法,对纳米晶粒长大行为进行了定量化和可视化的仿真研究.模拟结果表明,纳米晶粒长大的动力学与传统粗晶材料不同,在恒温条件下,纳米晶粒的长大指数n不是常数(传统粗晶材料的晶粒长大指数n=2为常数),随纳米晶粒长大过程的进行,n值从1.70至6.59发生变化.作为纳米晶粒长大的驱动力,纳米晶界的过剩自由能与纳米晶粒尺寸的变化直接相关.由于纳米晶材料强烈的小尺寸效应,纳米晶组织的热力学性质较大地影响纳米晶界的结构和能量状态,从而影响纳米晶粒长大的动力学特征.因此,只有结合纳米晶热力学特性的仿真研究才能获得对纳米晶粒长大行为本质性的认识.

用Cellular Automaton模型方法模拟二元合金多晶粒枝晶生长

研究并针对CellularAutomaton凝固组织模拟方法的物理本质、数值计算方法以及在凝固微观组织模拟中的应用进行了探索。并利用CellularAutomaton凝固组织模拟方法,求解了Al4.5Cu等轴晶多个枝晶同时生长过程。模拟结果和试验结果吻合很好。

采用Cellular Automaton法模拟铝合金的微观组织

采用 Cellular Automaton微观模型 ,并与宏观的传热计算相结合 ,对砂型铸造铝合金铸件的凝固组织形成进行了模拟。在模拟过程中 ,采用连续形核的方法处理液态金属的异质形核现象。通过高斯分布函数描述形核质点密度随温度的分布关系 ,在给定过冷度时对分布函数求积分可得该时刻的形核密度。晶粒生长模型则考虑枝晶尖端生长动力学和择优生长方向〈1 0 0〉晶向。模拟计算结果表明 ,在冷却速度不变的情况下 ,随着形核分布参数ΔTN 增加 ,所得到的晶粒尺寸增大。

VANET-Cellular环境下安全消息广播中继选择方法研究

当目标区域距离广播源节点过远时,基于机会网络的车联网安全消息广播算法往往造成过高的传输时延,难以保证安全消息的QoS需求.广泛部署的蜂窝移动网络为安全消息广播提供了一种新思路.基于VANETcellular网络架构,该文提出了一种安全消息广播中继节点选择方法.通过一种改进的RTS/CTS交互,根据候选车辆的蜂窝网络信号强度及其增量、链路稳定度、信道质量、地理位置等参数选出最佳的广播中继节点,并通过该节点将安全消息传递给服务器,最终由服务器传递给目标区域.数值分析和实验仿真结果显示,该方法不过分依赖于车流密度,也不需要额外部署基础设施,同时能够快速、可靠地传递安全消息,减少车载网络中信息冗余,提高了网络资源利用率.

采用Cellular automaton法模拟动态再结晶过程的研究

结合金属塑性成形过程的冶金学原理,给出了一种新的模拟动态再结晶过程的元胞自动机(Cellular automaton,CA)模型,用来模拟塑性变形过程中动态再结晶过程。再结晶晶粒的生长速度与再结晶驱动力成正比, 再结晶驱动力取决于晶界能和位错密度。在一个增量步内,根据动态再结晶晶粒生长速度确定与其相邻原胞转变 概率。采用本模型对不同温度、应变速度、应变条件下的动态再结晶过程进行了模拟,模拟结果与试验结果以及 经验公式得到的结果相一致。本模型也可用于再结晶动力学、微观组织和织构变化过程的模拟。

脊髓损伤后细胞自噬的调控治疗机制及策略

背景:细胞自噬通过自噬体-溶酶体降解途径来维持代谢和体内平衡,其与脊髓损伤后远端神经元细胞死亡和功能恢复受损密切相关,靶向细胞自噬来促进脊髓损伤后功能恢复是比较有前景的治疗方向。目的:对细胞自噬在脊髓损伤中的作用、细胞自噬的相关调控机制及治疗策略进行归纳总结。方法:以“spinal cord injury,autophagy,regulatory mechanisms,autophagy pathway,therapeutic target”为检索词,检索PubMed数据库;以“脊髓损伤,细胞自噬,调控机制,自噬通路,治疗靶点”为检索词,检索中国知网,最终纳入133篇英文文献和4篇中文文献。结果与结论:①细胞自噬作为细胞程序性死亡方式的一种,在脊髓损伤的进展和治疗中起着至关重要的作用。大多数研究表明,适度激活或促进自噬能够通过减少炎症反应和细胞凋亡来促进神经功能的恢复;少数研究表明,过度激活自噬相反,会阻碍脊髓损伤后的功能恢复。②脊髓损伤后,PI3K/AKT/mTOR、MAPK、AMPK、p53信号通路及Beclin-1、ATG和LC3等因子正向或负向调节细胞自噬的发生发展。③促进或抑制自噬可能是调控创伤性脊髓损伤发病机制的有前景的治疗策略,西药氨氯地平、二甲双胍、米诺环素,中医药山楂叶总黄酮、白桦脂酸、氧化苦参碱、针灸,以及细胞外囊泡、外泌体、活性氧响应的复合纤维等作为细胞自噬的激活剂,通过激活细胞自噬,减轻脊髓损伤的继发性损伤反应;而西药胰岛素样生长因子1、依拉达奉,中医药人参皂苷、针灸,以及水凝胶搭载碱性成纤维细胞生长因子作为细胞自噬的抑制剂,通过抑制过度的细胞自噬来促进脊髓损伤后的功能恢复。④细胞自噬的相关调控因子之间相互联系,而细胞自噬对于脊髓损伤的双向作用使得调控细胞自噬的主导因素尚需进一步探讨。⑤以自噬作为脊髓损伤治疗靶点的研究多在动物模型中进行,尚无应用于临床领域的自噬相关药物,其安全性和有效性还需进一步的临床研究。

富血小板血浆促进创面愈合的细胞和分子机制

背景:尽管富血小板血浆在促进创面愈合方面显示出治疗潜力,但其临床应用仍需要进一步的研究和验证。此外,对于富血小板血浆作用的机制仍存在一些争议和不确定性。目的:通过对富血小板血浆促进创面愈合的机制进行概述和分析,以增进对该治疗方法的理解,为未来的基础研究和临床应用提供有益的指导。方法:在中国知网、PubMed数据库检索2000年1月至2023年12月发表的相关文献。英文检索词为“platelet rich plasma,PRP,wound,wound healing,refractory wounds,chronic wounds,cellular and molecular mechanisms,signaling pathways,regenerative medicine”,中文检索词为“富血小板血浆,PRP,创面,伤口,创面愈合,难愈性创面,慢性创面,细胞和分子机制,信号通路,再生医学”。根据纳入和排除标准,最终对80篇文献进行综述。结果与结论:①富血小板血浆在创面愈合中具有许多潜在的优势,它能够提供丰富的生长因子和细胞因子等生物活性物质;②富血小板血浆可以调节参与创面愈合的各种细胞类型的功能,包括表皮细胞、血管内皮细胞、成纤维细胞、干细胞和炎症细胞等;③在富血小板血浆疗法中,细胞外囊泡、线粒体对于创面愈合可能扮演着重要角色;④负载富血小板血浆水凝胶可广泛用于增强组织再生和作为药物传递的功能性载体;⑤富血小板血浆对创面细胞外基质合成和降解起调节作用,从而影响伤口愈合过程中基质重建;⑥富血小板血浆可能通过动态调节多种信号通路和上皮间质转化来影响组织修复与再生,从而为创面愈合的研究提供了全新的视角。

用Cellular Automaton方法模拟压铸镁合金AM50的微观组织

基于Cellular Automaton(CA)方法的基本原理,建立了压铸镁合金AM50形核和等轴晶粒生长的二维数学物理模型,能够对任意晶向的等轴晶晶粒生长进行模拟。模型耦合了宏观传热与微观组织模拟计算,镁合金AM50阶梯块压铸件的温度场通过热传导反算法计算求得。对阶梯块压铸件不同阶梯表面的微观组织进行了模拟,并与金相试验结果进行了对比,它们在晶粒尺寸上吻合较好。

用Cellular Automaton模型方法模拟二元合金枝晶生长

研究并针对CellularAutomaton凝固组织模拟方法模型的物理本质、数值计算方法以及在凝固微观组织模拟中的应用进行了探索。并利用CellularAutomaton凝固组织模拟方法,求解了Al-4.5%Cu等轴晶枝晶生长。

单细胞转录组测序技术在脊髓损伤研究中的应用

背景:近年来,单细胞转录组测序技术在脊髓损伤的研究为创伤后中枢神经系统的细胞和分子异质性以及结构变化提供了新的见解。目的:就单细胞转录组测序技术在脊髓损伤的研究进展进行综述,更加全面、深入地阐述单细胞转录组测序技术在脊髓损伤领域的应用。方法:应用计算机系统检索PubMed、Web of Science、中国知网和万方数据库中2009-2023年出版的文献,英文检索词为“single-cell RNA sequencing,spinal cord injury,sequencing technology”;中文检索词为“单细胞转录组测序,脊髓损伤,测序技术”。排除质量较差、内容重复及不相关的文献,最终纳入57篇文献进行综述分析。结果与结论:目前,单细胞转录组测序技术在脊髓损伤的研究可归纳为以下几点:①鉴定了小胶质细胞、星形胶质细胞、少突胶质细胞、巨噬细胞、B细胞、神经元和神经干细胞等细胞亚群,并识别了这几种亚群的特异性标记基因。②小胶质细胞在脊髓损伤后保持永久活跃,通过增殖、免疫和稳态功能来协调脊髓损伤后的早期阶段。星形胶质细胞以激活的方式在脊髓损伤中发挥许多重要功能,包括维持微环境平衡、清除坏死组织、形成保护屏障以及胶质瘢痕等。巨噬细胞和小胶质细胞均在脊髓损伤后的慢性神经炎症中起重要作用。③神经干细胞和神经元亚群能够在脊髓损伤后进行自我更新,新发现的SCV^(sx2::Hoxa7:Zfhx3→lumbar)和SCV^(sx2::Hoxa10)等神经元亚群可再生到自然靶区,有利于运动功能的恢复。④发现细胞亚群的动态变化提高了研究者们对脊髓损伤病变进程的理解,并为脊髓损伤在不同时间点的治疗提供了新见解。截至目前,这些研究结果均还需要更多的基础研究和足够的临床试验来验证。在未来,单细胞转录组测序技术通过与生物信息学、计算机科学、组织工程学和临床医学等跨学科合作,有望为脊髓损伤的诊疗打开新的一扇窗户。

Cellular Automaton法模拟金属凝固显微组织研究进展

介绍了金属凝固过程中显微组织模拟的数学模型和计算模型以及元胞自动机(Cellular automation)法的原理及发展历程。概述了晶粒形核和生长的几个物理模型,并对元胞自动机在凝固过程中微观组织形成过程的计算机模拟的应用作了较详细的介绍。元胞自动机考虑了形核和生长动力学问题,通过宏微观耦合模型可计算固相分数和潜热释放的变化。介绍了两种元胞自动机和有限元方法的耦合方式,并对元胞自动机法的未来发展方向进行了展望。

Cellular Automaton法模拟铝合金微观组织的形成

采用Cellular Automaton微观模型,在给定冷却曲线的条件下,对铝合金板材凝固过程组织的形成进行了二维数值模拟。采用连续形核的方法处理液态金属的异质形核现象。用CA算法处理晶粒生长过程,考虑了枝晶尖端生长动力学和优先生长方向<100>晶向。通过模拟动态再现了凝固过程中晶粒的形核与生长。结果表明,在形核分布参数不变的情况下,随着冷却速度的增加,所得晶粒尺寸增大。

DNA-based vaccination induces humoral and cellular immune responses against hepatitis B virus surface antigen in mice without activation of Cmyc

AIM To develop a safe and effective DNAvaccine for inducing humoral and cellularimmunological responses against hepatitis Bvirus surface antigen(HBsAg).METHODS BALB/c mice were inoculated withNV-HB/s,a recombinant plasmid that had beeninserted S gene of hepatitis B virus genome andcould express HBsAg in eukaryotes.HBsAgexpression was measured by ABC immunohis-tochemical assay,generation of anti-HBs byELISA and cytotoxic T lymphocyte(CTL),byMTT method,existence of vaccine DNA bySouthern blot hybridization and activation ofoncogene C-myc by in situ hybridization,RESULTS With NV-HB/s vaccination byintramuscular injection,anti-HBs was initiallypositive 2 weeks after inoculation while all micetested were HBsAg positive in the muscles.Thetiters and seroconversion rate of anti-HBs weresteadily increasing as time went on and weredose-dependent.All the mice inoculated with100 μg NV-HB/s were anti-HBs positive onemonth after inoculation,the titer was 1:1024 ormore.The humoral immune response was similarinduced by either intramuscular or intradermalinjection.CTL activities were much stronger(45.26%)in NV-HB/s DNA immunized mice as compared with those(only 6%)in plasma-derived HBsAg vaccine immunized mice.Twomonths after inoculation,all muscle sampleswere positive by Southern-blot hybridization forNV.HB/s DNA detection,but decreased to 25%and all were undetectable by in situhybridization after 6 months.No oncogene C-myc activation was found in the muscle ofinoculation site.CONCLUSION NV-HB/s could generatehumoral and cellular immunological responsesagainst HBsAg that had been safely expressed insitu by NV-HB/s vaccination.

Mechanisms of resistance to sorafenib and the corresponding strategies in hepatocellular carcinoma

Sorafenib, the unique drug as first-line treatment for advanced hepatocellular carcinoma (HCC), has opened a window of hope after searching for effective agents to combat HCC for decades. However, the overall outcomes are far from satisfactory. One of the explanations is the genetic heterogeneity of HCC, which has led to identifying predictive biomarkers for primary resistance to sorafenib, and then applying the concept of personalized medicine, or seeking therapeutic strategies such as combining sorafenib with other anticancer agents. Some of the combinations have demonstrated a better effectiveness than sorafenib alone, with good tolerance. The acquired resistance to sorafenib has also drawn attention. As a multikinase inhibitor, sorafenib targets several cellular signaling pathways but simultaneously or sequentially the addiction switches and compensatory pathways are activated. Several mechanisms are involved in the acquired resistance to sorafenib, such as crosstalks involving PI3K/Akt and JAK-STAT pathways, hypoxia-inducible pathways, epithelial-mesenchymal transition, etc . Based on the investigated mechanisms,some other molecular targeted drugs have been applied as second-line treatment for treat HCC after the failure of sorafenib therapy and more are under evaluation in clinical trials. However, the exact mechanisms accounting for sorafenib resistance remains unclear. Further investigation on the crosstalk and relationship of associated pathways will better our understanding of the mechanisms and help to find effective strategies for overcoming sorafenib resistance in HCC.

Structural modeling of sandwich structures with lightweight cellular cores

An effective single layered finite element （FE） computational model is proposed to predict the structural behavior of lightweight sandwich panels having two dimensional （2D） prismatic or three dimensional （3D） truss cores. Three different types of cellular core topology are considered： pyramidal truss core （3D）, Kagome truss core （3D） and corrugated core （2D）, representing three kinds of material anisotropy： orthotropic, monoclinic and general anisotropic. A homogenization technique is developed to obtain the homogenized macroscopic stiffness properties of the cellular core. In comparison with the results obtained by using detailed FE model, the single layered computational model can give acceptable predictions for both the static and dynamic behaviors of orthotropic truss core sandwich panels. However, for non-orthotropic 3D truss cores, the predictions are not so well. For both static and dynamic behaviors of a 2D corrugated core sandwich panel, the predictions derived by the single layered computational model is generally acceptable when the size of the unit cell varies within a certain range, with the predictions for moderately strong or strong corrugated cores more accurate than those for weak cores.