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11.
Bela Anand-Apte Jennifer R. Chao Ruchira Singh Heidi Stöhr 《Journal of neuroscience research》2019,97(1):88-97
Sorsby fundus dystrophy (SFD), an autosomal dominant, fully penetrant, degenerative disease of the macula, is manifested by symptoms of night blindness or sudden loss of visual acuity, usually in the third to fourth decades of life due to choroidal neovascularization (CNV). SFD is caused by specific mutations in the Tissue Inhibitor of Metalloproteinase-3, (TIMP3) gene. The predominant histo-pathological feature in the eyes of patients with SFD are confluent 20–30 m thick, amorphous deposits found between the basement membrane of the retinal pigment epithelium (RPE) and the inner collagenous layer of Bruch's membrane. SFD is a rare disease but it has generated significant interest because it closely resembles the exudative or “wet” form of the more common age-related macular degeneration (AMD). In addition, in both SFD and AMD donor eyes, sub-retinal deposits have been shown to accumulate TIMP3 protein. Understanding the molecular functions of wild-type and mutant TIMP3 will provide significant insights into the patho-physiology of SFD and perhaps AMD. This review summarizes the current knowledge on TIMP3 and how mutations in TIMP3 cause SFD to provide insights into how we can study this disease going forward. Findings from these studies could have potential therapeutic implications for both SFD and AMD. 相似文献
12.
Y.R. Song B. Wu Y.T. Yang J. Chen L.J. Zhang Z.W. Zhang H.Y. Shi C.L. Huang J.X. Pan P. Xie 《Brazilian journal of medical and biological research》2015,48(11):973-982
Bipolar disorder (BD) is a common psychiatric mood disorder affecting more than 1-2%
of the general population of different European countries. Unfortunately, there is no
objective laboratory-based test to aid BD diagnosis or monitor its progression, and
little is known about the molecular basis of BD. Here, we performed a comparative
proteomic study to identify differentially expressed plasma proteins in various BD
mood states (depressed BD, manic BD, and euthymic BD) relative to healthy controls. A
total of 10 euthymic BD, 20 depressed BD, 15 manic BD, and 20 demographically matched
healthy control subjects were recruited. Seven high-abundance proteins were
immunodepleted in plasma samples from the 4 experimental groups, which were then
subjected to proteome-wide expression profiling by two-dimensional electrophoresis
and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight tandem
mass spectrometry. Proteomic results were validated by immunoblotting and
bioinformatically analyzed using MetaCore. From a total of 32 proteins identified
with 1.5-fold changes in expression compared with healthy controls, 16 proteins were
perturbed in BD independent of mood state, while 16 proteins were specifically
associated with particular BD mood states. Two mood-independent differential
proteins, apolipoprotein (Apo) A1 and Apo L1, suggest that BD pathophysiology may be
associated with early perturbations in lipid metabolism. Moreover, down-regulation of
one mood-dependent protein, carbonic anhydrase 1 (CA-1), suggests it may be involved
in the pathophysiology of depressive episodes in BD. Thus, BD pathophysiology may be
associated with early perturbations in lipid metabolism that are independent of mood
state, while CA-1 may be involved in the pathophysiology of depressive episodes. 相似文献
13.
皮肤损伤后的异常愈合会导致病理性瘢痕的产生。病理性瘢痕的出现不仅影响美观,严重时还会造成心理和生理功能障碍。病理性瘢痕的机制研究对于瘢痕治疗有极为重要的意义。其中,动物瘢痕模型是目前研究病理性瘢痕的重要模型手段之一。理想的动物瘢痕模型应该在组织学、细胞学等层面尽可能接近于人类的病理性瘢痕。该文分别从传统技术动物瘢痕中的啮齿类动物模型、兔耳模型和猪模型,以及新技术动物瘢痕模型这两个方面,结合近年来在瘢痕领域应用较多的研究,进行了相应系统的阐述。 相似文献
14.
复杂性胸壁缺损的修复一直是一项极具挑战性的工作。肿瘤性复杂性胸壁缺损的修复决策及其执行困难是限制胸壁肿瘤治疗方法选择及影响预后的重要因素之一。皮瓣解剖学研究的深入、胸壁支持结构重建技术的进步、显微外科技术的发展、麻醉护理的发展、对综合治疗的重视和治疗手段的进步等,使传统认为不可切除的胸壁肿瘤得以彻底地切除和安全有效地修复,从而使与缺损修复相关的肿瘤切除及辅助治疗的禁忌证缩减到最小程度,有效地提高了胸壁肿瘤患者的生存质量,并很大程度上延长了生存率。作者以湖南省肿瘤医院整形外科15年565例胸壁肿瘤切除后修复重建的临床资料为依据,充实了胸壁肿瘤切除及修复的策略:(1)可靠的胸壁骨性支架重建;(2)有效的软组织修复;(3)麻醉及护理与手术团队的合作;(4)系统有序的综合治疗。并进一步明确了复杂胸壁肿瘤切除及重建的细节理念,包括胸部肿瘤治疗中加强多学科合作的密切性和科学性,整形外科医生参与肿瘤治疗整体规划的主动性和时机前移等。 相似文献
15.
Sophocarpine attenuates toll‐like receptor 4 in steatotic hepatocytes to suppress pro‐inflammatory cytokines synthesis
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【目的】探讨中药淫羊藿、巴戟天提取物(中药注射液喘可治的组成)对恒河猴单核衍生的巨噬细胞在未极化(M0)、M1极化条件下基因表达的影响,分析其可能的免疫调节的作用机制。【方法】采用密度梯度离心法分离中国恒河猴外周血单个核细胞(PBMCs),采用贴壁法纯化出单核细胞,并以粒细胞巨噬细胞集落刺激因子(GM-CSF)刺激5 d以使单核细胞分化成巨噬细胞;然后不加入极化因子(M0)或以干扰素γ(IFN-γ,继续培养2 d)诱导巨噬细胞极化为M1表型,同时分别加入淫羊藿、巴戟天提取物进行干预;然后提取m RNA并逆转录后,采用实时荧光定量PCR检测CCR5、CD4、CTLA-4、Fox P3、IDO、IL-10、TGF-β等基因表达量。【结果】与空白对照组比较,加入巴戟天提取物培养的M0巨噬细胞基因表达上调不明显;经淫羊藿提取物培养的M0巨噬细胞,CCR5基因表达量上调4.21倍,TGF-β上调7.66倍,Fox P3、IL-10轻度上调,而CD4、CTLA-4、IDO等基因表达改变倍数无明显变化。经巴戟天提取物刺激的M1型巨噬细胞,CTLA-4基因表达量上调3.22倍,Fox P3上调3.69倍,CCR5、CD4、IL-10、IDO基因改变倍数均无明显变化,TGF-β未测出;而由淫羊藿提取物刺激的M1型巨噬细胞,IL-10的表达量上调11.83倍,Fox P3上调4.55倍,IDO、CCR5、CD4、CTLA-4基因改变倍数无明显变化,TGF-β未测出。【结论】巴戟天和淫羊藿提取物培养能够上调M1型巨噬细胞IL-10、Fox P3、CTLA-4等抑炎基因表达,淫羊藿提取物能够上调M0巨噬细胞CCR5和TGF-β等基因表达,促进病原体清除和组织修复,从而发挥多效免疫调节作用。 相似文献
19.
To evaluate the anthropometric indexes in subjects with varicocele compared to controls and the incidence of varicocele in different body mass index (BMI) groups for the purpose of exploring the association between varicocele and anthropometric indexes. A comprehensive literature search was conducted by using PubMed, MEDLINE, EMBASE databases and Cochrane Library up to February 2019. A systematic review and meta‐analysis was conducted by STATA, and Newcastle–Ottawa Scale was utilised for assessing risk of bias. Ultimately, 13 articles containing seven case–control studies and six cross‐sectional studies with 1,385,630 subjects were involved in our study. Pooled results demonstrated that varicocele patients had a lower BMI (WMD = ?0.77, 95% CI = ?1.03 to ?0.51) and a higher height than nonvaricocele participants, especially in grade 3 varicocele patients. Subgroup analyses showed that normal BMI individuals had a higher risk of varicocele than obese or overweight individuals and a lower risk than underweight individuals. In conclusion, this study indicates that varicocele patients have a lower BMI and a higher height than nonvaricocele participants. Moreover, men with excess bodyweight have a lower incidence of varicocele compared to normal weight or underweight people. That is to say, high BMI and adiposity protect against varicocele and high BMI is associated with a decreased risk of varicocele. 相似文献
20.
Shengxuan Cao Chen Wang Xin Ma Xu Wang Jiazhang Huang Chao Zhang Li Chen Xiang Geng Kan Wang 《Journal of orthopaedic research》2019,37(8):1860-1867
Patients with mechanic ankle instability experience increased tibiotalar and subtalar joint laxity. However, in vivo joint kinematics in functional ankle instability (FAI) patients and lateral ankle sprain (LAS) copers, especially during dynamic activities, are poorly understood. Ten FAI patients, 10 LAS copers, and 10 healthy controls were included in this study. A dual fluoroscopic imaging system was used to analyze the tibiotalar and subtalar joint kinematics during stair descent. Five key poses of stair descent were analyzed. Kinematic data from six degrees of freedom were calculated utilizing a solid modeling software. The range of motion and joint positions in each degree of freedom were compared among the three groups. The tibiotalar joints of FAI patients and LAS copers were significantly more inverted than those of healthy controls during the foot strike (p = 0.016, = 0.264). The subtalar joints of FAI patients were significantly more anteriorly translated (pose 2, p = 0.003, = 0.352; pose 3, p < 0.001, = 0.454; pose 4, p = 0.004, = 0.334), inverted (pose 4, p = 0.027, = 0.234; pose 5,p = 0.034, = 0.221), and externally rotated (pose 4, p = 0.037, = 0.217; pose 5; p = 0.004, = 0.331) than those of healthy controls during the mid‐stance and the heel off. The FAI patients showed excessive tibiotalar inversion and subtalar joint hypermobility during stair descent. Meanwhile, the LAS copers maintained subtalar joint stability, and only showed excessive tibiotalar inversion in foot strike. These data provide insight into the mechanisms behind the development of FAI after initial LAS. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1860–1867, 2019 相似文献