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In Silico Study to Evaluate the Inhibitory Activity of a Few Phenylethanoid Glycosides on GSK3-β Protein for Faster Diabetic Wound Healing 几种苯乙醇糖苷对糖尿病创面GSK3-β蛋白抑制作用的实验研究
Pub Date : 2023-03-08 DOI: 10.3390/ecb2023-14134
Ankit Majie, Rajdeep Saha, B. Sarkar
: Chronic wound resulting from diabetes mellitus is a significant cause of amputation world-wide. Secondary infections, lowering of nitric oxide synthase level, reduction of glucose-6-phosphate dehydrogenase levels, improper extracellular matrix remodelling, neuropathy, abnormality of endothelial cell function, and vasculopathy impedes the normal wound healing cycle during diabetes. Multiple studies have concluded that Ser9 phosphorylation causes inhibition of the glycogen synthase kinase-3 β (GSK3-β ) protein, which is essential for faster diabetic wound healing. Hence this protein could be a potential target for molecular interactions with prospective wound-healing molecules. Verbascoside, martynoside, echinacoside, crenatoside, and salidroside are a few phenylethanoid glycosides that have potential wound-healing ability by increasing extracellular matrix synthesis, angiogenesis, keratinocyte migration, and the functioning of macrophages and neutrophils. Thus, the five glycosides were subjected to molecular docking with GSK3-β protein (PDB ID: 1I09). This study revealed strong binding interactions with GSK3-β (between − 10.2 and − 7.3 kcal/mol) and inhibition constants (between 0.032 and 4.397 µ M) which suggested potent inhibition of the target protein even at lower concentrations of these compounds. Further, the docked complexes were visualized to find the interaction of the ligands with the amino acid residues. However, further in vivo and in vitro studies are required to validate the activity of these phenylpropanoid glycosides in diabetic wound healing.
糖尿病引起的慢性伤口是世界范围内截肢的重要原因。继发性感染、一氧化氮合酶水平降低、葡萄糖-6-磷酸脱氢酶水平降低、细胞外基质重构不当、神经病变、内皮细胞功能异常和血管病变阻碍了糖尿病患者正常的伤口愈合周期。多项研究表明,Ser9磷酸化导致糖原合成酶激酶-3 β (GSK3-β)蛋白的抑制,而GSK3-β蛋白是糖尿病伤口更快愈合所必需的。因此,这种蛋白质可能是与未来伤口愈合分子相互作用的潜在靶标。毛蕊花苷、马丁苷、紫锥花苷、桂皮苷和红景天苷是几种苯乙醇苷,它们通过增加细胞外基质合成、血管生成、角化细胞迁移以及巨噬细胞和中性粒细胞的功能而具有潜在的伤口愈合能力。因此,这五种糖苷与GSK3-β蛋白(PDB ID: 1I09)进行了分子对接。该研究发现,与GSK3-β的强结合相互作用(在−10.2和−7.3 kcal/mol之间)和抑制常数(在0.032和4.397µM之间)表明,即使在较低浓度的这些化合物下,也能有效抑制目标蛋白。此外,对对接的配合物进行可视化,以发现配体与氨基酸残基的相互作用。然而,需要进一步的体内和体外研究来验证这些苯丙苷在糖尿病伤口愈合中的活性。
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引用次数: 1
Neuroimmunomodulation in Chronic Wound Healing after Treatment with Photodynamic Therapy: The Role of iNOs 光动力治疗后慢性伤口愈合的神经免疫调节:iNOs的作用
Pub Date : 2023-03-08 DOI: 10.3390/ecb2023-14135
Lorenzo Notari, P. Nardini, V. Grandi, Alessandro Corsi, N. Pimpinelli, S. Bacci
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引用次数: 1
An In Silico Approach to Evaluate the Diabetic Wound Healing Potential of Phenylethanoid Glycoside in Inhibiting the Receptor for Advanced Glycation End Products (RAGE) 用计算机方法评价苯乙醇苷抑制晚期糖基化终产物受体(RAGE)对糖尿病创面愈合的影响
Pub Date : 2023-03-08 DOI: 10.3390/ecb2023-14137
Ritika Baidya, B. Sarkar
: Diabetes mellitus (DM) is a chronic metabolic disorder and is associated with impaired wound healing. Non-healing leg and foot ulcers are a frequent significant consequence of diabetes and are caused by a combination of inadequate tissue perfusion, suppression of re-epithelialization, and poor collagen production. Receptor for Advanced Glycation End Products (RAGE) is a multi-ligand cell surface molecule that belongs to the immunoglobulin superfamily and is crucial in the pathophysiology of poor wound healing in diabetics. By inhibiting RAGE, a chronic non-healing wound is more likely to undergo angiogenesis, enhance blood supply to hypoxic areas of the wound, and decrease the pro-inflammatory reaction and pro-apoptotic signaling. Phenylethanoid glycosides (PhGs) are a class of natural glycosides that possess anti-diabetic, wound-healing, antimicrobial, anti-inflammatory, and antioxidant properties. Echinacoside, a phenylethanoid glycoside, has a promising role in wound healing by enhancing angiogenesis, promoting keratinocyte migration and proliferation, and enhancing neutrophil and macrophage activity. Consequently, molecular docking was performed to assess the interaction between Echinacoside and the RAGE receptor (PDB ID: 6VXG). The ligand and receptor had a strong binding interaction, as indicated by the lowest binding energy, which was found to be − 6.1 kcal/mol. To further assess the activity of Echinacoside in diabetic wound healing, in vitro and in vivo studies are needed.
糖尿病(DM)是一种慢性代谢紊乱,与伤口愈合受损有关。无法愈合的腿脚溃疡是糖尿病常见的严重后果,是由组织灌注不足、再上皮化抑制和胶原蛋白生成不良共同引起的。晚期糖基化终产物受体(Receptor for Advanced Glycation End Products, RAGE)是一种多配体细胞表面分子,属于免疫球蛋白超家族,在糖尿病患者伤口愈合不良的病理生理中起着至关重要的作用。通过抑制RAGE,慢性不愈合创面更容易发生血管生成,增加创面缺氧区域的血供,减少促炎反应和促凋亡信号。苯乙醇糖苷(PhGs)是一类具有抗糖尿病、伤口愈合、抗菌、抗炎和抗氧化特性的天然糖苷。紫锥菊苷是一种苯乙醇苷,通过促进血管生成,促进角质细胞迁移和增殖,增强中性粒细胞和巨噬细胞活性,在伤口愈合中具有良好的作用。因此,我们进行了分子对接,以评估紫锥菊苷与RAGE受体(PDB ID: 6VXG)的相互作用。配体与受体具有较强的结合作用,最低结合能为−6.1 kcal/mol。为了进一步评估紫锥花苷在糖尿病创面愈合中的作用,还需要进行体内和体外研究。
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引用次数: 0
Proteomics Approaches for the Discovery of Potential Enzymatic Biomarkers for Early Diagnosis of Breast Cancer 发现乳腺癌早期诊断潜在酶生物标志物的蛋白质组学方法
Pub Date : 2023-03-02 DOI: 10.3390/ecb2023-14099
Yingxi Li, N. Hüttmann, Z. Minić, M. Berezovski
Breast cancer (BC) is one of the leading causes of death in Canadian women, with an average survival rate of 5 years after diagnosis. Early detection of BC can greatly improve patient outcomes and survival. However, a non-invasive BC detection method is not currently available in clinics. Recent studies suggest that proteins from small extracellular vesicles (sEVs) could be promising biomarkers for non-invasive BC early-stage diagnosis. sEVs are membrane-enclosed vesicles secreted by cells that drive different stages of carcinogenesis in BC. The purpose of this work was to analyze different published proteomics datasets to identify enzymes that could be potentially used as diagnostic biomarkers. Three cell line studies were compared, and overlapping BC proteins were highlighted with proteins found in sEVs from blood and plasma. In total, 106 proteins were selected based on the cell line studies, of which 40 have been identified in blood/plasma sEVs. These 106 proteins were mostly enriched with cell–cell signaling and DNA repair terms based on GO analysis. Furthermore, these 40 proteins contained 11 enzymes that can be explored as potential BC biomarkers. Future validation of enzymes using cancer cell lines and blood from BC patients remains to be determined.
乳腺癌(BC)是加拿大妇女死亡的主要原因之一,诊断后的平均生存率为5年。早期发现BC可以极大地改善患者的预后和生存率。然而,目前临床上还没有一种非侵入性的BC检测方法。最近的研究表明,来自小细胞外囊泡(sev)的蛋白质可能是无创BC早期诊断的有希望的生物标志物。sev是由细胞分泌的膜封闭囊泡,在BC中驱动不同阶段的癌变。这项工作的目的是分析不同的已发表的蛋白质组学数据集,以确定可能用作诊断性生物标志物的酶。比较了三种细胞系的研究,发现重叠的BC蛋白与血液和血浆中sev中发现的蛋白相突出。根据细胞系研究,总共选择了106种蛋白质,其中40种在血液/血浆sev中被鉴定出来。根据氧化石墨烯分析,这106个蛋白大多富含细胞-细胞信号和DNA修复术语。此外,这40种蛋白含有11种酶,可以作为潜在的BC生物标志物。使用癌细胞系和BC患者血液的酶的未来验证仍有待确定。
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引用次数: 0
Effects of RF Currents on Cytokines Production in Human Keratinocytes 射频电流对人角质形成细胞细胞因子产生的影响
Pub Date : 2023-03-01 DOI: 10.3390/ecb2023-14096
M. L. Hernández-Bule, Elena Toledano-Macías, María Antonia Martínez-Pascual, A. Úbeda, M. Fernández-Guarino
: Wound healing consists of a sequence of coordinated phases: inflammation, proliferation, and remodeling. In skin lesions, neutrophils and keratinocytes are the main cell types participating in the inflammatory phase, during which the release of mediators intervening in the regulation of the subsequent regenerative phases takes place. These mediators are involved in tissue regeneration through induction of transendothelial migration, enzyme secretion, cell adhesion, and T-Cell activation and cytotoxicity, as well as neutrophil accumulation at the wound site. Among these mediators, the keratinocyte-synthesized chemokines RANTES, MCP-1, MIP-1, and IL-8 stand out. Although therapies applying electromagnetic fields or electric currents have been shown to have anti-inflammatory effects in a variety of experimental models and in patients through reduced production of proinflammatory cytokines such as IFN-Υ and increased production of IL-10, the knowledge on the biological basis of these effects is still limited. Previous studies by our group have shown that subthermal treatment with radiofrequency (RF) currents used in capacitive-resistive electric transfer (CRET) therapy promotes the proliferation and migration of various cell types, such as human ADSC (stem cells), fibroblasts or keratinocytes, involved in skin regeneration. This study investigates the effects of in vitro treatment with CRET currents on cytokine production by HaCat human keratinocytes. The results reveal that, compared to sham-exposed controls, RF stimulation induces decreased production of IL-8 and RANTES and increased MCP-1, without significantly affecting other chemokines such as MIP-1. Taken together, our results indicate that due to the RF effects on the production of chemokines involved in the modulation of the inflammatory phase of wound regeneration, CRET therapy could be effective in the treatment of skin wounds.
伤口愈合包括一系列协调的阶段:炎症、增殖和重塑。在皮肤病变中,中性粒细胞和角质形成细胞是参与炎症期的主要细胞类型,在此期间,介导调节随后再生期的介质的释放发生。这些介质通过诱导跨内皮迁移、酶分泌、细胞粘附、t细胞活化和细胞毒性以及伤口部位的中性粒细胞积累参与组织再生。在这些介质中,角化细胞合成的趋化因子RANTES、MCP-1、MIP-1和IL-8尤为突出。尽管应用电磁场或电流的疗法已在各种实验模型和患者中显示出通过减少促炎细胞因子如IFN-Υ的产生和增加IL-10的产生而具有抗炎作用,但关于这些作用的生物学基础的知识仍然有限。我们小组之前的研究表明,在容电阻电转移(CRET)治疗中使用射频(RF)电流进行亚热治疗,可促进各种细胞类型的增殖和迁移,如参与皮肤再生的人类ADSC(干细胞)、成纤维细胞或角质形成细胞。本研究探讨了体外CRET电流对HaCat人角质形成细胞产生细胞因子的影响。结果显示,与假暴露对照组相比,射频刺激诱导IL-8和RANTES的产生减少,MCP-1的产生增加,而对MIP-1等其他趋化因子没有显著影响。综上所述,我们的研究结果表明,由于射频对参与伤口再生炎症期调节的趋化因子的产生有影响,CRET治疗可能有效地治疗皮肤伤口。
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引用次数: 0
Experimental Identification of Aberrantly Expressed Long Non-Coding RNAs in Breast Cancer 乳腺癌中异常表达的长链非编码rna的实验鉴定
Pub Date : 2023-03-01 DOI: 10.3390/ecb2023-14083
I. Pronina, S. Lukina, V. Loginov, A. Burdennyy, T. Kazubskaya, E. Braga, E. Filippova
Breast cancer (BC) remains one of the leading causes of cancer deaths among women worldwide. Recently, studies of long non-coding RNAs (lncRNAs) involved in the regulation of various signaling pathways in cells have become increasingly important, since they demonstrate great prognostic potential in cancer. The aim of our work was to identify new aberrantly expressed lncRNAs in BC. We identified 30 aberrantly expressed lncRNAs in BC. For most lncRNAs, a decrease in the expression level by 2.34–13.2 times (p < 0.05) was noted, and only for lncRNA TERC, an increase in the expression level by 2.24 times (p = 0.034) was noted. Of greatest interest are the data obtained for the lncRNAs ADAMTS9-AS2, EMX2OS, HOTAIRM1 and MEG3, as they are consistent with the data of the bioinformatic analysis.
乳腺癌(BC)仍然是全世界妇女癌症死亡的主要原因之一。近年来,长链非编码rna (long non-coding RNAs, lncRNAs)参与细胞中各种信号通路的调控,由于其在癌症中显示出巨大的预后潜力,对其的研究变得越来越重要。我们工作的目的是鉴定BC中新的异常表达的lncrna。我们在BC中发现了30个异常表达的lncrna。大多数lncRNA的表达量下降了2.34 ~ 13.2倍(p < 0.05),只有lncRNA TERC的表达量增加了2.24倍(p = 0.034)。最令人感兴趣的是获得的lncRNAs ADAMTS9-AS2、emx2s、HOTAIRM1和MEG3的数据,因为它们与生物信息学分析的数据一致。
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引用次数: 0
Nepeta nuda L. Plant Extract Preserves the Morphology of Red Blood Cells Subjected to Oxidative Stress 荆芥提取物对氧化应激下红细胞形态的保护作用
Pub Date : 2023-03-01 DOI: 10.3390/ecb2023-14086
S. Petrova, Nikol Mazhdrakova, S. Todinova, V. Strijkova, M. Zhiponova, S. Krumova
.net/. Abstract: We show that an extract from catmint ( Nepeta nuda L.) flowers is not hemotoxic and does not alter erythrocytes’ morphology. H 2 O 2 -induced oxidative stress leads to an increase in lipid peroxidation, accompanied by a reduction in the number of biconcave cells and an increase in the number of echinocytes. Pre-treatment of erythrocytes with this extract does not reduce the lipid peroxidation level; however, it results in partial restoration of the relative abundance of biconcave cells and a respective reduction in the echinocytes’ quantity. Our data reveal the concentrations at which the examined extract exhibits a protective effect on erythrocytes’ morphology under the condition of H 2 O 2 -induced oxidative stress.
.net/。摘要:本研究表明,猫薄荷(Nepeta nuda L.)花提取物不具有血液毒性,也不改变红细胞形态。h2o2诱导的氧化应激导致脂质过氧化的增加,伴随着双凹细胞数量的减少和棘细胞数量的增加。用这种提取物预处理红细胞不会降低脂质过氧化水平;然而,它导致双凹细胞相对丰度的部分恢复,而刺突细胞的数量相应减少。我们的数据显示,在所检测的提取物浓度下,在h2o2诱导的氧化应激条件下,对红细胞形态有保护作用。
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引用次数: 0
Generation of iPSC-Derived RGCs for Modeling Dominant Optic Atrophy 生成ipsc衍生的RGCs用于模拟显性视神经萎缩
Pub Date : 2023-03-01 DOI: 10.3390/ecb2023-14087
Marta García-López, M. E. Gallardo
: Dominant optic atrophy (DOA), mainly caused by pathogenic variants in OPA1 , is one of the most common forms of hereditary optic neuropathy. OPA1 is involved in mitochondrial dynamics and oxidative phosphorylation, among other functions. Hence, mutations in this gene cause the degeneration of retinal ganglion cells (RGCs), leading to reduced visual acuity. In this work, we have used induced pluripotent stem cell (iPSC) technology to generate RGCs, starting from an iPSC line created from fibroblasts from a DOA patient and also its CRISPR isogenic control. The generated RGCs showed expression of BRN3A, SNCG or THY1, and could potentially serve as a platform for DOA modeling.
显性视神经萎缩(DOA)是遗传性视神经病变最常见的形式之一,主要由OPA1的致病变异引起。OPA1参与线粒体动力学和氧化磷酸化等功能。因此,该基因的突变导致视网膜神经节细胞(RGCs)变性,导致视力下降。在这项工作中,我们使用了诱导多能干细胞(iPSC)技术来生成RGCs,从DOA患者的成纤维细胞和其CRISPR等基因对照中创建的iPSC系开始。生成的RGCs表达BRN3A、SNCG或THY1,可以作为DOA建模的潜在平台。
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引用次数: 0
Research into New Molecules with Anti-Inflammatory Activity 抗炎新分子的研究
Pub Date : 2023-03-01 DOI: 10.3390/ecb2023-14095
Abel Vale, M. Lucas, D. Ribeiro, E. Fernandes
: The drugs currently available as cyclooxygenase-2 (COX-2) inhibitors increase the risk of cardiovascular events, which justifies the search for new alternative anti-inflammatory molecules. This work aimed to evaluate the anti-inflammatory activity of the chalcones (polyhydroxylated aromatic compounds): 2 (cid:48) ,3,4,4 (cid:48) ,6 (cid:48) -pentahydroxychalcone (5OH), 2 (cid:48) ,3,4,4 (cid:48) ,6 (cid:48) -pentamethoxychalcone (5OMe), and 2 (cid:48) ,3,4,4 (cid:48) -tetrahydroxychalcone (butein), at non-cytotoxic concentrations, in an experimental human whole blood model. The results obtained showed that none of the chalcones under study was cytotoxic to human blood cells. From the tested chalcones, butein was the only one showing a concentration-dependent inhibitory production of prostaglandin E 2 , via COX-2, in human blood (40 ± 8%, at 50 µ M).
目前可用的环氧化酶-2 (COX-2)抑制剂增加了心血管事件的风险,这证明了寻找新的替代抗炎分子的合理性。本工作旨在评价查尔酮(多羟基化芳香化合物):2 (cid:48),3,4,4 (cid:48),6 (cid:48) -五羟基查尔酮(5OH), 2 (cid:48),3,4,4 (cid:48),6 (cid:48) -五甲基查尔酮(5OMe)和2 (cid:48),3,4,4 (cid:48) -四羟基查尔酮(丁蛋白)在实验人体全血模型中的抗炎活性。结果表明,所研究的查尔酮对人体血细胞没有细胞毒性。在所测试的查尔酮中,丁蛋白是唯一一种在人血液中通过COX-2抑制前列腺素e2产生的浓度依赖性物质(40±8%,50µM)。
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引用次数: 0
Signature Garlic Phytochemical as a Potential Anti-Candidal Candidate Targeting Virulence Factors in Candida albicans  大蒜植物化学标志作为潜在的抗白色念珠菌毒力因子候选物
Pub Date : 2023-03-01 DOI: 10.3390/ecb2023-14080
Z. Hasan, A. Islam, L. Khan
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引用次数: 0
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The 2nd International Electronic Conference on Biomedicines
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