Modulation of p75 neurotrophin receptor mitigates brain damage following ischemic stroke in mice

Stroke is a significant leading cause of death and disability in the United States(Tsao et al.,2022).Approximately 87% of strokes fall into the ischemic category,mainly caused by arterial blockage(Jayaraj et al.,2019).Although the only FDA-approved effective medication is tissue plasminogen activator(tPA),it should be administrated within 4.5 hours of ischemic stroke.Furthermore,tPA has been an integral part of managing acute ischemic stro ke.

Pre-B-cell colony-enhancing factor as a target for protecting against apoptotic neuronal death and mitochondrial damage in ischemia

Focal ischemic stroke（FIS）results from the lack of blood flow in a particular region of the brain and accounts for about 80%of all human strokes.Although tremendous efforts have been made in translational research,the treatment strategies are still limited.Tissue plasminogen activator is the only FDA-approved drug currently available for acute stroke treatment,

Delayed neural damage induced by lightning and electrical injury: neural death, vascular necrosis and demyelination?

The structural damage to vascular endothelial cell In a recent article in the journal Brain Injury, four potential hypotheses for delayed neurological disorders following lightning and electrical injury were suggested （Reisner, 2013）. The phenomenon of delayed neurodegenerative syndromes following lighting and electrical injury has been known since the early 1930s （Critchley, 1934）, but to the present day, the mechanisms involved have been poorly un- derstood. An initial and still plausible theory is that the electrical insult causes damage to the vascular structures feeding the spinal cord via damage to vascular endothelial cells （Farrell and Starr, 1968）.

光动力治疗与肿瘤细胞免疫原性死亡

抗癌治疗的成功依赖于免疫系统介导的长期特异性抗肿瘤免疫反应。而近年来肿瘤细胞免疫原性死亡(ICD)被认为是诱发机体产生这种反应的重要方式。光动力疗法(PDT)已被证实可引发肿瘤细胞免疫原性死亡。ICD的核心是垂死癌细胞表达或释放危险相关分子模式(DAMPs),这些DAMPs对激活树突状细胞(DC)和激活T细胞适应性免疫反应至关重要,并导致长期免疫记忆的形成。本文将介绍ICD的研究进展以及通过改善肿瘤微环境缺氧和光敏剂的亚细胞定位增强PDT诱导ICD的能力的探索。

《民法典》第1179条第2句(残疾赔偿、死亡赔偿)评注

《民法典》第1179条第2句第2分句不仅仅是进一步明确法律效果的辅助规范**,也是进一步明确单纯侵害民事利益侵权责任的构成要件的辅助规范。《人身损害赔偿司法解释》对残疾赔偿金、丧葬费、死亡赔偿金、被扶养人生活费的计算进行了定额处理。定额赔偿的本质是不考虑被侵权人本人情况客观计算损害。残疾赔偿金、死亡赔偿金有广狭义之分。广义残疾赔偿金、死亡赔偿金代表了被侵权人的全部收入损失,包含被扶养人生活费,而不能与被扶养人生活费赔偿并存;狭义残疾赔偿金、死亡赔偿金只是被侵权人收入损失的一部分,与被扶养人生活费赔偿并存不会导致重复赔偿。扶养期限既取决于被扶养人需要他人扶养的期限,更取决于扶养人(被侵权人)能够扶养他人的期限。被扶养人生活费是被侵权人的部分收入损失,被侵权人的收入期限直接决定了扶养期限。被侵权人的收入期限应当与残疾赔偿金、死亡赔偿金的赔偿期限一致。

Autophagy in neuroinflammation after traumatic brain injury

Traumatic brain injury(TBI)is an acquired injury of the brain caused by the impact of external forces on the brain(Maas et al.,2008).It is a major cause of death and disability among people of all ages(Maas et al.,2008).The primary mechanical injury to the brain initiates a cascade of secondary biochemical events that lead to acute and chronic neurodegeneration and activation of inflammatory pathways(Maas et al.,2008).Both brain-resident microglia and blood-derived myeloid cells-macrophages and monocytes that infiltrate the brain due to injury-induced blood-brain barrier damage,contribute to the inflammatory responses after TBI(Morganti et al.,2015).

HARA效用下考虑DC养老金带有死亡和伤残返还条款的最优投资问题

考虑了一个带有死亡和伤残返还的DC型养老金计划的最优投资问题。以终端财富期望效用最大化为目标,利用动态规划原理建立相应的Hamilton-Jacobi-Bellman(HJB)方程,在双曲绝对风险厌恶(HARA)效用函数下得到最优解,通过数值模拟分析重要参数对最优投资策略的影响。

铁死亡在肿瘤免疫中的作用研究进展

铁死亡(ferroptosis)是由亚铁离子和脂质过氧化物过量堆积所导致的新型细胞死亡模式,能够以自噬依赖的方式释放损伤相关分子模式,作为免疫原性细胞死亡的佐剂,激活适应性免疫和固有免疫。肿瘤细胞和免疫细胞铁死亡受多种因素的调控且相互影响,对肿瘤的发展、治疗和预后起着重要作用。文中总结了肿瘤微环境中,T细胞、巨噬细胞、中性粒细胞、 B细胞等免疫细胞与肿瘤细胞铁死亡之间的相关生物学效应。

新生儿缺氧缺血性脑损伤程序性细胞死亡及康复治疗干预机制的研究进展

新生儿缺氧缺血性脑损伤(HIBD)是一种脑细胞缺血缺氧性坏死病变,可导致神经发育性残疾,降低儿童生存质量,给患儿家庭及社会带来沉重负担。程序性细胞死亡(PCD)作为一种重要的神经元细胞死亡调控机制,参与HIBD的发生发展。康复治疗是改善HIBD后功能障碍的主要干预方式,临床应用广泛,但其效应机制目前尚未完全阐明。康复治疗可调控PCD,是促进HIBD后功能恢复的关键。因此,深入研究PCD特别是凋亡、自噬、焦亡、铁死亡在HIBD中的作用机制及康复干预机制,可以为疾病的治疗提供新思路。

预制破片对2种姿态人体目标的毁伤效果研究

为能够精确地评估预制破片对人体目标的毁伤效果,对破片场的飞散过程进行数值模拟,利用Matlab编程提取破片相关信息,计算得到破片射击迹线,据此建立战斗部-人体目标交汇模型,确定每枚破片命中的人体部位,利用A-S准则计算出失能概率。将地面区域网格化,按照一定距离步长,改变人体模型位置,重复上述计算流程,得到每个网格位置处的失能概率,构成毁伤矩阵,通过毁伤矩阵计算得出有效毁伤面积。设置不同的战斗部落角、落速、炸高,研究预制破片对2种人体姿态的毁伤效果。结果表明:在落角0°~80°,采用蹲姿的毁伤面积减少了6%~16%,在落角大于40°,蹲姿的腿部及头部被击中数明显低于站姿;在落速100~700 m/s,相比于站姿,蹲姿的毁伤面积降低8%~11%,破片击中数也始终低于站姿;在炸高2~4.6 m,蹲姿的毁伤面积降低8%~20%,破片击中数始终低于站姿。在战场上,战斗人员采用蹲姿,一定程度上可以降低被破片击中的概率,降低战斗人员的失能概率,减少毁伤面积。

氧化应激降低鸡肉品质的作用机制研究进展

肉鸡氧化应激的诱发因素愈加广泛且复杂,造成机体不同程度的氧化损伤,最终影响到家禽健康和产品品质。肉鸡对氧化应激尤为敏感,肉鸡的肉品质下降很大程度上与氧化应激条件下面临的氧化损伤危害增大有关,因此揭示氧化应激影响鸡肉品质形成的内在机制具有重要意义。本文从肉鸡的能量代谢、钙离子代谢和细胞凋亡3个方面,深入介绍了肌肉中氧化损伤的发生机制,可为揭示氧化应激造成鸡肉品质下降的作用机制和肉鸡生产中应激环境控制提供理论基础。

免疫原性细胞死亡在肺癌治疗中的研究进展

肺癌是一种发病率和致死率均较高的恶性肿瘤,具有分型多、恶性程度高及预后不良等特点。免疫疗法通过激发和增强机体的免疫功能,达到控制和杀伤肿瘤细胞的目的,已被证实对多种类型的恶性肿瘤具有良好的治疗效果。免疫原性细胞死亡(immunogenic cell death,ICD)是一种程序性细胞死亡方式,其特点是损伤相关分子模式(damage-associated molecular patterns,DAMPs)的大量释放。在经过某些化疗药物、物理疗法、生物疗法或联合治疗后,肺癌细胞会发生ICD,由非免疫原性转变为免疫原性,进而募集和活化免疫细胞,最终激活和增强机体抗肿瘤免疫应答。该文就ICD的发生机制以及ICD在肺癌治疗中的应用作一综述。

坏死性凋亡分子机制及与牙周炎的相关性

背景:近年来,随着细胞死亡研究的不断深入,坏死性凋亡逐渐成为学术界研究的热点和难点,其多种信号通路及蛋白在牙周炎的发生发展中起到不可忽视的作用,人们试图通过阻止细胞坏死性凋亡的发生,从而延缓牙周组织炎症的进程。目的:就坏死性凋亡的分子机制及其与牙周炎的相关性进行综述,期望为牙周炎的预防、诊断、治疗及预后提供新思路、新方向。方法:第一作者于2023年10月应用计算机检索PubMed、中国知网等数据库建库到2024年4月发表的相关文献,以“坏死性凋亡,细胞程序性死亡,牙周炎,牙周,免疫,炎症,受体相互作用蛋白激酶1,受体相互作用蛋白激酶3,混合系列蛋白激酶样结构域”为中文检索词;“necroptosis,programmed cell death,periodontitis,periodontal,immunity,inflammation,RIP1,RIP3,MLKL”为英文检索词,阅读每篇文献的文题、摘要、引言进行初步筛选,最终纳入56篇文献进行总结分析。结果与结论:①牙周炎的主要发病机制为牙周致病菌刺激机体,导致牙周微环境发生改变,打破原有免疫平衡并释放各种炎症因子,引发炎症反应造成牙周组织破坏,坏死性凋亡可以调控牙周组织免疫炎症反应,从而影响牙周炎的发生发展进程;②坏死性凋亡的发生与多种蛋白、信号通路及信号分子有关,已有动物实验证实了磷酸化混合系列蛋白激酶样结构域(pMLKL)的表达量与炎症程度有关,且在患有牙周炎小鼠的牙周组织中,RIP3和pMLKL高表达,通过阻断RIP3/MLKL通路,有利于减少牙周组织炎症、控制牙周炎的进展;③探究pMLKL是否可作为牙周炎的诊断指标,在牙周炎的预防、诊断及治疗上有很大价值。

重金属Pb^(2+)、Cd^(2+)、Cr^(6+)对洞庭青鲫仔鱼急性毒性、细胞凋亡及组织损伤的影响

研究重金属Pb^(2+)、Cd^(2+)、Cr^(6+)对洞庭青鲫(Carassius auratus indigentiaus)仔鱼的毒性效应。选择不同浓度的Pb^(2+)、Cd^(2+)、Cr^(6+)处理洞庭青鲫仔鱼,分别在实验的0、24、48、72、96 h观察重金属离子对仔鱼死亡率的影响。选择96 h低死亡率重金属浓度处理组(2 mg·L^(-1)Pb^(2+)、0.125 mg·L^(-1)Cd^(2+)、5 mg·L^(-1)Cr6+),观察各重金属对洞庭青鲫仔鱼鳃组织损伤及细胞凋亡的影响。结果表明:(1)Pb^(2+)、Cd^(2+)、Cr^(6+)对洞庭青鲫仔鱼的96-LC_(50)分别为39.5、0.39、16.38 mg⋅L^(-1),安全浓度分别为3.945、0.039、1.638 mg·L^(-1)。急性毒性由强至弱依次为Cd^(2+)>Pb^(2+)>Cr^(6+);(2)5 mg·L^(-1)Cr^(6+)处理组洞庭青鲫仔鱼96 h死亡率为37%,仔鱼鳃组织产生严重损伤,包括细胞纹理变得疏松,色素细胞大量增加,纤毛脱落,大量细胞空泡化,巨噬细胞增多,结缔组织发生糜烂坏死等。2 mg⋅L^(-1)Pb^(2+)和0.125 mg⋅L^(-1)Cd^(2+)处理组洞庭青鲫仔鱼96 h死亡率分别为16%和58%,仔鱼鳃组织出现轻微损伤,色素细胞少量增加,少量细胞出现空泡化;(3)2 mg⋅L^(-1)Pb^(2+)、0.125 mg⋅L^(-1)Cd^(2+)、5 mg⋅L^(-1)Cr^(6+)三个处理组的洞庭青鲫仔鱼鳃部发生细胞凋亡,并且Pb^(2+)处理组鳃部细胞凋亡最严重。综上所述,Pb^(2+)、Cd^(2+)、Cr^(6+)对洞庭青鲫仔鱼具有较强的毒性,但是各重金属处理组死亡率与组织损伤、细胞凋亡无显著的相关性,不同重金属导致洞庭青鲫死亡的机制可能不一样。

肺癌治疗新方向:细胞免疫原性死亡

肺癌是全球范围内发病率和死亡率增长最快,对人类生命威胁最大的恶性肿瘤之一。被诊断为肺癌的患者通常会接受多种治疗,包括手术、化疗和/或放射治疗、免疫治疗及靶向治疗;然而,肺癌五年生存率仍然很低,特别是当癌症已达到晚期或发生远处转移时。因此,必须开发更有效、更新颖的技术来解决这个问题。免疫原性细胞死亡(immunogenic cell death,ICD)的诱导剂应用已被证明可以增强接受各种类型治疗患者的免疫力。ICD是指一种触发对死细胞抗原,特别是来自癌细胞的抗原的免疫反应的细胞死亡类型,它最初是关于使用传统细胞毒性药物进行抗癌化疗的效果提出的。本研究的目的是回顾和讨论ICD作为肺癌有前途的联合免疫疗法的作用和机制。

复杂交通事故中死亡与事故间因果关系鉴定

在多车连环碰撞的复杂交通事故中,多次碰撞引起二次损伤致人死亡的案件并不少见,此类事故在雨雪天气或夜间时段的高速公路夜间时段更易发生。因涉及车辆多,事故形态复杂,确定人员死亡与各次事故间的因果关系,对于厘清事故责任具有重要意义。为此,通过对一起实际事故案例的分析,对复杂交通事故中二次损伤与死亡的因果关系进行论证探讨,为今后开展此类案件的鉴定工作提供可参考的鉴定思路及分析方法。

早期康复护理对控制急性脑血栓患者残疾率及神经损伤程度的作用分析

目的 分析早期康复护理对急性脑血栓患者残疾率、神经损伤程度的影响。方法 抽取2022年1月—2023年1月本院收治的急性脑血栓患者60例为研究对象,以随机信封法分成参照组(n=30,常规护理)和观察组(n=30,早期康复护理),对比护理结果。结果 干预后,观察组患者NIHSS评分、残疾率、SAS评分、SDS评分均低于参照组(P<0.05);Fugl-Meyer评分、Barthel评分均高于参照组(P<0.05)。结论 早期康复护理可有效改善急性脑血栓患者神经功能受损的情况,降低残疾率,改善患者不良情绪,具有较高应用价值。

Neuron-specific enolase in cerebrospinal fluid as a biomarker of brain damage in infants with hypoxic-ischemic encephalopathy

Neonatal encephalopathy resulting from an asphyxial episode occurring perinatally is a major cause of death and of permanent neurological disabilities worldwide. Therapeutic hypothermia(TH) started within 6 hours of life and maintained for 72 hours is now well established as standard treatment for infants with moderate-to-severe hypoxicischemic encephalopathy(HIE).

Anti-malaria drug artesunate protects bronchial epithelium from DNA damage induced by asthma

OBJECTIVE To investigate the genome protective effects of anti-malaria drug,artesunate in an experimental allergic asthma model.METHODS Mice were sensitized on day 0 and 7 and challenged on day 14 with 100μg house dust mite(HDM)via intratracheal administration.Artesunate(30mg·kg-1)was administered intra-peritoneally on day 6,7,8,13,14 and 15.Samples were collected on day 1,3 and 5 post last HDM-challenge for analysis of air way inflammation and DNA damage.Lung sections were immunofluorescence(IF)-stained for DNA double strand breaks(DSBs)markers,γH2AX and 53BP1.Levels of DNA repair proteins Ku70 and Rad51,which are involved in non-homologous end joining(NHEJ)and homologous recombination(HR)DNA DSB repair pathways respectively,were measured.To quantify cell death in asthmatic lung,TUNEL staining was performed.Comet assay,a single cell gel electrophoresis was employed to detect DNA damage induced by HDM in BEAS-2Bhuman bronchial epithelial cell line,in vitro.RESULTS Artesunate treatment significantly reduces immune cells infiltration in BAL fluid of asthmatic mice,collected on day 3 and 5 post-challenge.Importantly,artesuante is able to protect bronchial epithelium from DNA DSBs induced by asthma,as detected by the reduced level of γH2AX and 53BP1 foci formation in the nucleus.This genome protective effect is evident even on day 1 post-challenge,when immune cells infiltration remained high.This indicates that artesunate confers protection on bronchial epithelium in the presence of inflammation.Additionally,artesunate is also able to reduce cell death in asthmatic lung revealed by TUNEL assay and cleaved caspase 3 level.Interestingly,the levels of DNA repair proteins in artesuante-treated asthmatic mice are unchanged as compared to HDM-only mice,suggesting that artesunate treatment does not augment the level of DNA repair proteins.When human bronchial epithelial BEAS-2 Bcells were exposed to HDMin vitro,we observed an increase in the levels of DNA damage.Artesunate(60μmol·L-1)co-incubated with HDM is not able to prevent direct DNA damage induced by the allergen.Together,these studies suggest that the genome protective effect of artesunate in vivo may be attributed to physiological effects(such as its anti-inflammatory effects)rather than serving to directly prevent DNA damage.CONCULSION This study highlights a novel role for artesunate in protecting bronchial epithelial cells from asthma-induced DNA damage.

Experimental model of photo-oxidative damage

Background:Retinal degeneration is a common feature of several retinal diseases,such as retinitis pigmentosa and age-related macular degeneration(AMD).In this respect,experimental models of photo-oxidative damage reproduce faithfully photoreceptor loss and many pathophysiological events involved in the activation of retinal cell degeneration.Therefore,such models represent a useful tool to study the mechanisms related to cell death.Their advantage consists in the possibility of modulating the severity of damage according to the needs of the experimenter.Indeed,bright light exposure could be regulated in both time and intensity to trigger a burst of apoptosis in photoreceptors,allowing the study of degenerative mechanisms in a controlled fashion,compared to the progressive and slower rate of death in other genetic models of photoreceptor degeneration.Methods:Here,an exemplificative protocol of bright light exposure in albino rat is described,as well as the main outcomes in retinal function,photoreceptor death,oxidative stress,and inflammation,which characterize this model and reproduce the main features of retinal degeneration diseases.Discussion:Models of photo-oxidative damage represent a useful tool to study the mechanisms responsible for photoreceptor degeneration.In this respect,it is important to adapt the exposure paradigm to the experimental needs,and the wide range of variables and limitations influencing the final outcomes should be considered to achieve proper results.Trial Registration:None.