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91.
92.
Mitochondrial membrane protein-associated neurodegeneration (MPAN) is an autosomal recessive disorder caused by mutation in the C19orf12 gene. We report a compound heterozygous c.[32C>T];[205G>A;424A>G] (p.[Thr11Met];[Gly69Arg;Lys142Glu]) Czech patient who manifested with right foot dystonia, impaired handwriting, attention deficit, and signs of iron accumulation on brain MRI. Gradually, he developed dysarthria, spastic-dystonic gait, pedes cavi, and atrophy of leg muscles. Additionally, we report demographic parameters, clinical signs, and allelic frequencies of C19orf12 mutations of all published MPAN cases. We compared the most frequent mutations, p.Thr11Met and p.Gly69ArgfsX10; the latter was associated with younger age at onset and more frequent optic atrophy in homozygotes. 相似文献
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94.
A natural antioxidant,tannic acid mitigates iron‐overload induced hepatotoxicity in Swiss albino mice through ROS regulation 下载免费PDF全文
《Environmental toxicology》2018,33(5):603-618
Tannic acid (TA), a water soluble natural polyphenol with 8 gallic acids groups, is abundantly present in various medicinal plants. Previously TA has been investigated for its antimicrobial and antifungal properties. Being a large polyphenol, TA chelates more than 1 metal. Hence TA has been explored for potent antioxidant activities against reactive oxygen species (ROS), reactive nitrogen species (RNS) and as iron chelator in vitro thereby mitigating iron‐overload induced hepatotoxicity in vivo. Iron dextran was injected intraperitoneally in Swiss albino mice to induce iron‐overload triggered hepatotoxicity, followed by oral administration of TA for remediation. After treatment, liver, spleen, and blood samples were processed from sacrificed animals. The liver iron, serum ferritin, serum markers, ROS, liver antioxidant status, and liver damage parameters were assessed, followed by histopathology and protein expression studies. Our results show that TA is a prominent ROS and RNS scavenger as well as iron chelator in vitro. It also reversed the ROS levels in vivo and restricted the liver damage parameters as compared to the standard drug, desirox. Moreover, this natural polyphenol exclusively ameliorates the histopathological and fibrotic changes in liver sections reducing the iron‐overload, along with chelation of liver iron and normalization of serum ferritin. The protective role of TA against iron‐overload induced apoptosis in liver was further supported by changed levels of caspase 3, PARP as well as Bax/BCl‐2 ratio. Thus, TA can be envisaged as a better orally administrable iron chelator to reduce iron‐overload induced hepatotoxicity through ROS regulation. 相似文献
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96.
背景 脂质蓄积指数(LAP)和内脏脂肪指数(VAI)是反映个体脂肪分布及内脏脂肪蓄积程度的重要指标,与肥胖相关的慢性代谢性疾病关系密切。目的 探讨LAP和VAI与成年人代谢综合征(MS)的相关性,并评估LAP、VAI对MS的预测价值。方法 纳入2018年9月至2019年5月在中日友好医院体检中心进行体检的708例受试者,其中MS患者249例(MS组),非MS患者459例(非MS组),比较两组患者LAP、VAI及相关生化指标。根据LAP、VAI四分位数将受试者进行分组(L1组、L2组、L3组、L4组各177例;V1组、V2组、V3组、V4组各177例),比较各组MS及其组分发生率。采用多因素Logistic回归分析计算不同LAP、VAI受试者MS的发生风险,并分别绘制不同性别LAP、VAI、腰围(WC)、体质指数(BMI)预测MS发生风险的受试者工作特征(ROC)曲线。结果 LAP和VAI与成年人MS发生率呈高强度正相关(Cramer's V=0.585、0.577)。多因素Logistic回归分析结果显示,在调整各危险因素后,L3组、L4组MS发生风险仍高于L1组,V3组、V4组MS发生风险仍高于V1组(P<0.001)。ROC曲线分析结果显示,男性LAP、VAI预测MS发生风险的ROC曲线下面积(AUC)分别为0.831〔95%CI(0.795,0.867)〕、0.825〔95%CI(0.788,0.863)〕,临界值分别为52.03、1.99;女性LAP、VAI预测MS发生风险的AUC分别为0.887〔95%CI(0.834,0.940)〕、0.886〔95%CI(0.827,0.945)〕,临界值分别为54.84、2.54。结论 LAP、VAI与成年人MS发生率呈高强度正相关,随着LAP、VAI增高,MS发生风险亦增高;LAP、VAI对MS有良好的预测价值,联合WC和BMI能有效预测MS。 相似文献
97.
Maria Domenica Cappellini John B. Porter Vip Viprakasit Ali T. Taher 《Blood reviews》2018,32(4):300-311
Beta-thalassaemia causes defective haemoglobin synthesis leading to ineffective erythropoiesis, chronic haemolytic anaemia, and subsequent clinical complications. Blood transfusion and iron chelation allow long-term disease control, and haematopoietic stem cell transplantation offers a potential cure for some patients. Nonetheless, there are still many challenges in the management of beta-thalassaemia. The main treatment option for most patients is supportive care; furthermore, the long-term efficacy and safety of current therapeutic strategies are limited and adherence is suboptimal. An increasing understanding of the underlying molecular and cellular disease mechanisms plus an awareness of limitations of current management strategies are driving research into novel therapeutic options. Here we provide an overview of the current pathophysiology, clinical manifestations, and global burden of beta-thalassaemia. We reflect on what has been achieved to date, describe the challenges associated with currently available therapy, and discuss how these issues might be addressed by novel therapeutic approaches in development. 相似文献
98.
《Research in microbiology》2016,167(7):613-623
Eight strains of acidophilic bacteria, isolated from mine-impacted and geothermal sites from different parts of the world, were shown to form a distinct clade (proposed genus “Acidibacillus”) within the phylum Firmicutes, well separated from the acidophilic genera Sulfobacillus and Alicyclobacillus. Two of the strains (both isolated from sites in Yellowstone National Park, USA) were moderate thermophiles that oxidised both ferrous iron and elemental sulphur, while the other six were mesophiles that also oxidised ferrous iron, but not sulphur. All eight isolates reduced ferric iron to varying degrees. The two groups shared <95% similarity of their 16S rRNA genes and were therefore considered to be distinct species: “Acidibacillus sulfuroxidans” (moderately thermophilic isolates) and “Acidibacillus ferrooxidans” (mesophilic isolates). Both species were obligate heterotrophs; none of the eight strains grew in the absence of organic carbon. “Acidibacillus” spp. were generally highly tolerant of elevated concentrations of cationic transition metals, though “A. sulfuroxidans” strains were more sensitive to some (e.g. nickel and zinc) than those of “A. ferrooxidans”. Initial annotation of the genomes of two strains of “A. ferrooxidans” revealed the presence of genes (cbbL) involved in the RuBisCO pathway for CO2 assimilation and iron oxidation (rus), though with relatively low sequence identities. 相似文献
99.
目的 探讨我国弓形虫Chinese 1优势基因型感染对宿主脑组织铁代谢及脑损伤的影响。方法 将20只C57BL/6(体质量15~17 g)小鼠随机分为对照组和感染组,每组10只。感染组每只小鼠腹腔注射4 000个弓形虫Chinese 1优势基因型TgCtwh3虫株速殖子,对照组小鼠注射等量无菌PBS,饲养6 d后处死小鼠并取其脑组织。采用电感耦合等离子体质谱法(inductively coupled plasma mass spectrometry, ICP⁃MS)检测小鼠脑组织铁元素水平;采用RNA芯片检测两组小鼠脑组织差异基因数目并对功能基因表达情况进行基因本体论(Gene Ontology, GO)功能富集;采用实时荧光定量PCR(fluorescent quantitative real⁃time PCR, qPCR)技术检测小鼠脑组织中弓形虫表面抗原1(Toxoplasma gondii surface antigen 1,TgSAG1)基因及部分锌铁调控蛋白(Zrt⁃ and Irt⁃like protein, ZIP)家族mRNA表达水平;采用光镜和电镜观察小鼠脑组织海马齿轮回(dentate gyrus, DG)超微结构;采用Western blotting检测谷胱甘肽过氧化物酶4(glutathione peroxidase 4, GPx4)蛋白表达水平;采用硫代巴比妥酸(TBA)法检测丙二醛(malondialdehyde, MDA)水平;采用免疫组化检测血管内皮生长因子(vascular endothelial growth factor, VEGF)蛋白表达光密度(optical density, OD)值。结果 光镜下可见感染组小鼠脑组织海马DG区细胞坏死,电镜下见感染组小鼠脑组织海马区出现胞质空泡化、核皱缩坏死、线粒体嵴断裂消融、自噬小体增加等超微结构变化。与对照组相比,感染组小鼠脑组织中铁元素水平上调[(32.92 ± 0.90) µg/g vs.(37.72 ± 1.10) µg/g;t = 3.397, P < 0.01];RNA芯片检测感染组小鼠脑组织发现721个基因上调、276个基因下调,差异表达基因在金属离子结合能力上有明显富集。与对照组相比,感染组小鼠脑组织金属元素转运体ZIP2 mRNA表达水平上调(t = 8.659,P < 0.05)、GPx4表达下降[(1.046 ± 0.025) vs. (0.720 ± 0.101);t = 3.129,P < 0.01])、MDA水平升高[(4.37 ± 0.33) nmol/mgprot vs.(5.93 ± 0.54) nmol/mgprot;t = 2.451,P < 0.05)]、VEGF蛋白平均OD值上调[(0.348 3 ± 0.017 8) vs. (0.490 6 ± 0.010 5);t = 6.641,P < 0.01]。结论 Chinese 1优势基因型弓形虫感染后,小鼠脑组织中铁元素蓄积、抗氧化能力下调、氧化应激水平升高,提示弓形虫感染可影响宿主脑组织铁代谢而导致脑损伤。 相似文献
100.
《Transfusion Clinique et Biologique》2020,27(3):128-132
We retrospectively assessed the characteristics of 165 MDS patients from our institution having received at least 20 RBC units. In the vast majority of them various comorbidities (range: 1–6 per patient) were registered including mainly cardiovascular disorders. Serum ferritin was over 1000 μg/L in about half of tested individuals. A chelator agent was initiated in 43.6% of patients (mainly low-risk MDS). Transformation in AML occurred in 46 cases (27.8%). Overall, 112 patients died during follow up. The cause of death was documented in 65 cases and included mainly MDS or AML resistance to therapy. There was a context of bacterial or fungal-related sepsis in 35.3% of cases. We noticed a correlation between survival and number of RBC transfusions. Median OS from the 20th RBC unit was significantly prolonged among the chelated subgroup. Consequences of transfusional iron overload and chelation need to be clarified in MDS patients. 相似文献