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41.
The Bruch’s membrane (BrM) is a five-layered extracellular matrix (ECM) that supports the retinal pigment epithelium (RPE). Normal age-related changes in the BrM may lead to RPE cell damage and ultimately to the onset and progression of age-related macular degeneration (AMD), which is the most common cause of visual loss among the elderly. A role for the complement system in AMD pathology has been established, but the disease mechanisms are poorly understood, which hampers the design of efficient therapies to treat millions of patients. In an effort to identify the mechanisms that lead from normal aging to pathology, we have developed a cell-based model using complement deficient human induced pluripotent stem cell (iPSC)-derived RPE cells cultured on an AMD-like ECM that mimics BrM. The data present evidence that changes in the ECM result in loss of differentiation and promote epithelial mesenchymal transition (EMT) of healthy RPE cells. This pathological process is mediated by complement activation and involves the formation of a randomly oriented collagen meshwork that drives the dedifferentiation of the RPE monolayer. Genetic ablation of complement component 3 has a protective effect against EMT but does not prevent the abnormal deposition of collagens. These findings offer new insights into the sequence of events that initiate AMD and may guide the design of efficient therapies to treat this disease with unmet medical needs. 相似文献
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Michael H. Guerra Thangal Yumnamcha Lalit P. Singh Ahmed S. Ibrahim 《International journal of molecular sciences》2021,22(15)
Disruption of retinal pigment epithelial (RPE) barrier integrity is involved in the pathology of several blinding retinal diseases including age-related macular degeneration (AMD) and diabetic retinopathy (DR), but the underlying causes and pathophysiology are not completely well-defined. Mitochondria dysfunction has often been considered as a potential candidate implicated in such a process. In this study, we aimed to dissect the role of different mitochondrial components; specifically, those of oxidative phosphorylation (OxPhos), in maintaining the barrier functionality of RPE. Electric cell-substrate impedance sensing (ECIS) technology was used to collect multi-frequency electrical impedance data to assess in real-time the barrier formation of the RPE cells. For this purpose, the human retinal pigment epithelial cell line—ARPE-19—was used and treated with varying concentrations of specific mitochondrial inhibitors that target different steps in OxPhos: Rotenone for complex I (the largest protein complex in the electron transport chain (ETC)); oligomycin for ATP synthase; and carbonyl cyanide-p-trifluoromethoxyphenyl hydrazone (FCCP) for uncoupling ATP synthesis from the accompanying ETC. Furthermore, data were modeled using the ECIS-Zθ software to investigate in depth the effects of these inhibitors on three separate barrier parameters: cell–cell interactions (Rb), cell–matrix interactions (α), and the cell membrane capacitance (Cm). The viability of ARPE-19 cells was determined by lactate dehydrogenase (LDH) Cytotoxicity Assay. The ECIS program’s modeling demonstrated that FCCP and thus OxPhos uncoupling disrupt the barrier function in the ARPE-19 cells across all three components of the total resistance (Rb, α, and Cm) in a dose-dependent manner. On the other hand, oligomycin and thus ATP synthase inhibition mostly affects the ARPE-19 cells’ attachment to their substrate evident by a significant decrease in α resistance in a dose-dependent manner, both at the end and throughout the duration of the experiment. On the contrary, rotenone and complex I inhibition mostly affect the ARPE-19 paracellular resistance Rb in a dose-dependent manner compared to basolateral resistance α or Cm. Our results clearly demonstrate differential roles for different mitochondrial components in maintaining RPE cell functionality in which uncoupling of OxPhos is a major contributing factor to the disruption barrier function. Such differences can be used in investigating gene expression as well as for screening of selective agents that improve the OxPhos coupling efficiency to be used in the therapeutic approach for treating RPE-related retinal diseases. 相似文献
44.
酸性矿山废水(AMD)排放量大、酸性强、盐度高、成分复杂,是难以处理的工业废水。介绍了近些年来处理酸性矿山废水技术进展,对中和沉淀法、铁氧体沉淀法、吸附法、湿地法、微生物法等处理技术的优点和缺点进行评价。对酸性矿山废水处理技术发展趋势及前景做了展望。 相似文献
45.
Samina Khalid Muhammad Usman Akram Tehmina Shehryar Waqas Ahmed Marium Sadiq Mahak Manzoor Nelam Nosheen 《International journal of imaging systems and technology》2021,31(1):236-252
Impairment to macula can cause loss of central vision. There are various macular disorders that can affect macular region and if not treated at an early stage can cause irreversible central vision loss. Age‐related macular degeneration (AMD) disorder is one of the most threading macular disorder. Bright lesion, drusens presence in macular region is known as the hallmark of AMD disorder. This bright lesion differentiation from other bright lesion like exudates is important for accurate diagnosis of AMD. Focus of this article is automated diagnosis of affected macular region by applying a hybrid features set containing textural, color, and structural/shape features for more accurate detection of AMD at an early stage using fundus images. These features also help to distinguish drusens from exudates. The proposed algorithm at first stage, detect macular region from input fundus image and then perform features extraction based on textural pattern, edge, and structural properties of macular region to classify abnormal macula from normal macula. For classification, we have used support vector machine (SVM), K‐nearest neighbor and neural networks but SVM classifier achieves high accuracy. The proposed algorithm is tested on publicly available STARE and locally available AFIO datasets. Attained sensitivity, specificity, and accuracy of our proposed system are 97.5%, 95% and 95.45%, respectively, when applied on STARE dataset. When we have applied our proposed system on AFIO dataset, we have attained sensitivity, specificity, and accuracy of 93.3%, 92% and 92.34%, respectively. 相似文献
46.
磁处理对番茄幼苗MDH合成的影响 总被引:2,自引:0,他引:2
经磁处理的番茄(Lycopersicon esculeutum mill)幼苗苹果酸脱氢酶(malate dehydrogenase,MDH)活性增高,同工酶谱发生变化,出现新谱带.加放线菌素D(actinomycin D,AMD)后磁处理同工酶带中的新带消失,表明磁处理可能改变了基因表达的调控.而加AMD的磁处理组酶活仍高于相应的对照组,推测磁处理有可能对幼苗体内已有的MDH有活化作用. 相似文献
47.
Bench-scale study of active mine water treatment using cement kiln dust (CKD) as a neutralization agent 总被引:1,自引:0,他引:1
The overall objective of this study was to investigate the potential impact on settled water quality of using cement kiln dust (CKD), a waste by-product, to replace quicklime in the active treatment of acidic mine water. Bench-scale experiments were conducted to evaluate the treatment performance of calcium hydroxide (Ca(OH)2) slurries generated using four different CKD samples compared to a control treatment with quicklime (CaO) in terms of reducing acidity and metals concentrations in acid mine drainage (AMD) samples taken from the effluent of a lead/zinc mine in Atlantic Canada. Results of the study showed that all of the CKD samples evaluated were capable of achieving greater than 97% removal of total zinc and iron. The amount of solid alkaline material required to achieve pH targets required for neutralization of the AMD was found to be higher for treatment with the CKD slurries compared to the quicklime slurry control experiments, and varied linearly with the free lime content of the CKD. The results of this study also showed that a potential benefit of treating mine water with CKD could be reduced settled sludge volumes generated in the active treatment process, and further research into the characteristics of the sludge generated from the use of CKD-generated calcium hydroxide slurries is recommended. 相似文献
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Abstract.
We investigated the treatment of acid mine drainage (AMD) by a blue-green algae-microbial consortium and substrate (containing powdered goat manure, wood chips, and soil) in 1 m3 bench scale biological treatment test cells. The microbial mat resulted from the interaction of bacteria and filamentous blue-green algae (predominantly Oscillatoria spp). The experiments were carried out for different water column heights, and were evaluated for 24, 48, 72, 96, and 168 hours of retention. Within 24 hours of retention, the pH increased from 2.93 to 6.78 as net alkalinity went from -125 mg/L to 197 mg/L as CaCO3. Turbidity decreased by 33–54%, sulphate decreased by 23–29%, and hardness decreased by 19 to 26%. We also observed that: 95% of the Fe, 79–97% of the Cu, 84–86% of the Zn, 88% of the Pb, 59–83% of the Co, 22–62% of the Ni, and 28–45% of the Mn were removed. A blue-green algae/microbial mat consortium may be a cost–effective treatment technique for removing metals from AMD. 相似文献
50.
Knight JC Hallett AJ Brancale A Paisey SJ Clarkson RW Edwards PG 《Chembiochem : a European journal of chemical biology》2011,12(17):2692-2698
AMD3100 is a potent and selective antagonist of the CXCR4 receptor; it has been shown to block the route of entry of HIV into host T-cells. This compound and its analogues have since been found to act as haematopoietic stem cell mobilisation agents and, more recently, as anti-cancer agents. Here, we have examined a fluorescent derivative of AMD3100, L(1), which offered the potential to assess the behaviour of AMD3100 at the cell surface by using optical imaging modalities. The binuclear Zn(II) , Cu(II) and Ni(II) complexes of L(1) have also been investigated as these metals have been previously shown to enhance the binding properties of AMD3100. Furthermore, Zn(II) and Cu(II) are known to enhance and quench, respectively, the fluorescence of similar anthracenyl-based ligands. Whilst L(1) demonstrates an ability to inhibit the binding of the anti-CXCR4 monoclonal antibody 12G5 (IC(50) =0.25-0.9 μM), the incorporation of an anthracenyl moiety resulted in a significantly reduced affinity for CXCR4 compared to AMD3100 (IC(50) =10 nM). We observed no significant increase in fluorescence intensity following incubation with murine pre-B cells overexpressing CXCR4 compared to a control cell line. This limits the usefulness of L(1) as a fluorescent imaging probe. Interestingly, the Zn(II) complex, which carries an overall +4 charge, revealed marginally higher specificity and reduced toxicity in vitro compared to the free ligand, albeit with reduced affinity for CXCR4 (IC(50) =1.8-5 μM). We suggest that the incorporation of an anthracenyl group contributes to the lipophilic character of the free ligand, thereby resulting in transport across the plasma membrane. This effect is seemingly diminished when the ligand is complexed to charged metal ions. 相似文献