Aβ1-42对大鼠脑组织SOD、GSH-Px活性及MDA含量的影响

目的 探究Aβ1-42寡聚体对大鼠大脑的氧化应激损伤的影响.方法 经过Morris水迷宫实验,挑选出逃避潜伏期少于60s的60只实验大鼠随机等分为4组,设为正常组、PBS对照组、Aβ1-42纤维组、Aβ1-42寡聚体组.将Aβ1-42纤维或Aβ1-42寡聚体注射于大鼠右侧脑室制成实验动物模型;PBS对照组采用同样的方法给予注射等量的PBS;正常组不作任何处理.使用可见分光光度计检测大鼠脑组织的超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)的活性变化及丙二醛(MDA)的含量水平变化情况.借助于光学显微镜观察苏木精-伊红(HE)染色的各组大鼠海马组织的形态学变化.结果 与正常组及PBS组比较,Aβ1-42纤维组和Aβ1-42寡聚体组大鼠皮质MDA含量(分别为7.826±1.696、11.247±1.948)及海马MDA(分别为9.818±1.900、15.090±2.425)含量增加(P<0.05),皮质SOD(分别为29.829±6.340、18.649±6.070)和海马SOD(分别为51.097±8.381、31.634±8.680)活性下降(P<0.05),皮质GSH-Px(分别为133.113±17.506、79.503±19.936)和海马GSH-Px(分别为154.819±23.688、102.800±28.332)活性下降(P<0.05),其中,以Aβ1-42寡聚体组的变化更明显.HE染色可知,Aβ1-42纤维体及Aβ1-42寡聚体可使大鼠大脑海马区的神经元损伤,其中,Aβ1-42寡聚体对神经元的毒性损伤作用更严重.结论 Aβ1-42纤维、Aβ1-42寡聚体都可通过氧化应激损伤引起大鼠脑组织神经元的损伤,以Aβ1-42寡聚体氧化损伤作用更大.     

MicroRNA-33/33* inhibit the activation of MAVS through AMPK in antiviral innate immunity

Innate immunity plays a prominent role in the host defense against pathogens and must be precisely regulated. As vital orchestrators in cholesterol homeostasis, microRNA-33/33* have been widely investigated in cellular metabolism. However, their role in antiviral innate immunity is largely unknown. Here, we report that VSV stimulation decreased the expression of miR-33/33* through an IFNAR-dependent manner in macrophages. Overexpression of miR-33/33* resulted in impaired RIG-I signaling, enhancing viral load and lethality whereas attenuating type I interferon production both in vitro and in vivo. In addition, miR-33/33* specifically prevented the mitochondrial adaptor mitochondrial antiviral-signaling protein (MAVS) from forming activated aggregates by targeting adenosine monophosphate activated protein kinase (AMPK), subsequently impeding the mitophagy-mediated elimination of damaged mitochondria and disturbing mitochondrial homeostasis which is indispensable for efficient MAVS activation. Our findings establish miR-33/33* as negative modulators of the RNA virus-triggered innate immune response and identify a previously unknown regulatory mechanism linking mitochondrial homeostasis with antiviral signaling pathways.     

Induced regulatory T cells suppress Tc1 cells through TGF-β signaling to ameliorate STZ-induced type 1 diabetes mellitus

Type 1 diabetes mellitus (T1D) is a chronic autoimmune condition in which the immune system destroys insulin-producing pancreatic β cells. In addition to well-established pathogenic effector T cells, regulatory T cells (Tregs) have also been shown to be defective in T1D. Thus, an increasing number of therapeutic approaches are being developed to target Tregs. However, the role and mechanisms of TGF-β-induced Tregs (iTregs) in T1D remain poorly understood. Here, using a streptozotocin (STZ)-induced preclinical T1D mouse model, we found that iTregs could ameliorate the development of T1D and preserve β cell function. The preventive effect was associated with the inhibition of type 1 cytotoxic T (Tc1) cell function and rebalancing the Treg/Tc1 cell ratio in recipients. Furthermore, we showed that the underlying mechanisms were due to the TGF-β-mediated combinatorial actions of mTOR and TCF1. In addition to the preventive role, the therapeutic effects of iTregs on the established STZ-T1D and nonobese diabetic (NOD) mouse models were tested, which revealed improved β cell function. Our findings therefore provide key new insights into the basic mechanisms involved in the therapeutic role of iTregs in T1D.     

Potential therapeutic effect and methods of traditional Chinese medicine on COVID-19-induced depression: A review

COVID-19 (coronavirus) has spread all over the world with a high infection rate. Currently, there are no targeted therapeutic drugs for COVID-19 as well as for stress induced by COVID-19. The unpredictable events of COVID-19 can trigger feelings of fear, worry, or unease in people, leading to stress-related disorders such as depression and anxiety. It has been reported that individuals, including COVID-19 patients, medical staff, and ordinary people, are under both physical and psychological pressure, and many of them have developed depression or anxiety during this pandemic. Traditional Chinese medicine (TCM) has been widely used in treating depression with relatively better safety and efficacy and may have an important role in treating stress-related disorders induced by COVID-19. In this review, we collected the common TCM treatment methods including Qigong, Acupuncture, Five Elements Musical Therapy, Five Elements Emotional Therapy, and Chinese herbal medicine from the databases of PubMed and the China National Knowledge Internet to illustrate the effect of TCM on depression. The better knowledge of TCM and implementation of TCM in COVID-19 clinics may help to effectively improve depression induced by COVID-19, may assist people to maintain a healthy physical and mental quality, and may alleviate the current shortage of medical resources.     

人体赤足形态特征接触面积与身高体质量相关性统计分析

背景:当前法医人类学、人体工程学及足迹学研究均发现足部各信息(如足长、足宽等)与身高、体质量呈现出显著相关性,但国内外文献对有关赤足形态特征接触面积与人体身高、体质量的量化研究尚不完善。目的:分析人体赤足形态特征接触面积与身高、体质量之间相关性,创新法医人类学、人体工程学等相关学科理论体系,为利用赤足足迹进行人身个体识别提供参考。方法:采用足迹学传统平面足迹油墨捺印方法进行样本收集,再利用MATLAB数字软件对足迹对象进行图像处理。测试对象为随机抽取身高分布在165-190 cm之间健康的青壮年男性100名,记录其身高、体质量,获取正常行走步态下的赤足形态特征接触面积并进行统计分析。试验的实施符合《赫尔辛基宣言》和中国刑事警察学院对人体研究的相关伦理要求。结果与结论:在健康青壮年男性正常弓类型(排除中断弓和膨胀弓两种弓区类型)条件下:①人体赤足形态特征接触面积与身高、体质量之间均呈显著正相关(P<0.01),其与人体身高之间关系可被应用于法医人类学、人体工程学、足迹学的身高分析;②身高相较于体质量而言,对人体赤足形态特征接触面积的影响更加显著,更具有直接相关性。     

Tree-based exploration of the optimization objectives for automatic cervical cancer IMRT treatment planning

Objective:To develop and evaluate a practical automatic treatment planning method for intensity-modulated radiation therapy (IMRT) in cervical cancer cases.Methods:A novel algorithm named as Optimization Objectives Tree Search Algorithm (OOTSA) was proposed to emulate the planning optimization process and achieve a progressively improving IMRT plan, based on the Eclipse Scripting Application Programming Interface (ESAPI). 30 previously treated cervical cancer cases were selected from the clinical database and comparison was made between the OOTSA-generated plans and clinical treated plans and RapidPlan-based (RP) plans.Results:In clinical evaluation, compared with plan scores of the clinical plans and the RP plans, 22 and 26 of the OOTSA plans were considered as clinically improved in terms of plan quality, respectively. The average conformity index (CI) for the PTV in the OOTSA plans was 0.86 ± 0.01 (mean ± 1 standard deviation), better than those in the RP plans (0.83 ± 0.02) and the clinical plans (0.71 ± 0.11). Compared with the clinical plans, the mean doses of femoral head, rectum, spinal cord and right kidney in the OOTSA plans were reduced by 2.34 ± 2.87 Gy, 1.67 ± 2.10 Gy, 4.12 ± 6.44 Gy and 1.15 ± 2.67 Gy. Compared with the RP plans, the mean doses of femoral head, spinal cord, right kidney and small intestine in the OOTSA plans were reduced by 3.31 ± 1.55 Gy, 4.25 ± 3.69 Gy, 1.54 ± 2.23 Gy and 3.33 ± 1.91 Gy, respectively. In the OOTSA plans, the mean dose of bladder was slightly increased, with 2.33 ± 2.55 Gy (versus clinical plans) and 1.37 ± 1.74 Gy (vs RP plans). The average elapsed time of OOTSA and clinical planning were 59.2 ± 3.47 min and 76.53 ± 5.19 min.Conclusion:The plans created by OOTSA have been shown marginally better than the manual plans, especially in preserving OARs. In addition, the time of automatic treatment planning has shown a reduction compared to a manual planning process, and the variation of plan quality was greatly reduced. Although improvement on the algorithm is warranted, this proof-of-concept study has demonstrated that the proposed approach can be a practical solution for automatic planning.Advances in knowledge:The proposed method is novel in the emulation strategy of the physicists’ iterative operation during the planning process. Based on the existing optimizers, this method can be a simple yet effective solution for automated IMRT treatment planning.     

Activation of dopaminergic VTA inputs to the mPFC ameliorates chronic stress-induced breast tumor progression

AimsChronic stress plays an important role in promoting the progression and migration of cancers. However, little is known of any direct impact on tumor progression related to the regulation of emotion‐related circuitry. The aim of this study was to explore the neural‐circuit mechanisms underlying stress‐induced progression of cancers and the impact of emotion‐related regulation of circuitry on tumor growth.MethodsOptogenetic manipulation was applied to unpredictable chronic mild stress (UCMS)–treated mice bearing breast tumor cell. The stress‐related hormones, tumor‐related cytokines, the tyrosine hydroxylase (TH)–positive neurons and their fibers, dopamine receptor–positive cells, and anxiety level were measured using ELISA, immunohistochemical staining, fluorescence in situ hybridization, and behavioral test, respectively.ResultsBy investigating breast cancer mouse models with a chronic mild stress model, optogenetic stimulation, and behavioral analysis, we show that chronic stress induced anxiety‐like behavior in mice and increased serum concentration of norepinephrine and corticosterone, hormones closely related to stress and anxiety. Optogenetic activation of VTA TH terminals in the mPFC rescued anxiety‐like behavior induced by chronic stress. Chronic stress resulted in marked progression of breast tumors, and repetitive optogenetic activation of VTA TH terminals in the mPFC significantly attenuated stress‐induced progression of breast cancers and reduced serum concentration of norepinephrine and corticosterone. Furthermore, there was a positive correlation between serum norepinephrine or corticosterone concentration and tumor size.ConclusionsThese findings indicate a positive role of an emotion regulation circuit on the progression of breast cancer and reveal a link between stress, emotion regulation, and the progression of breast cancers. Our findings provide new insights pertinent to therapeutic interventions in the treatment of breast cancers.