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101.
Elena V. Rosca Marie-France Penet Noriko Mori Jacob E. Koskimaki Esak Lee Niranjan B. Pandey Zaver M. Bhujwalla Aleksander S. Popel 《PloS one》2014,9(11)
We investigated the application of a mimetic 20 amino acid peptide derived from type IV collagen for treatment of breast cancer. We showed that the peptide induced a decrease of proliferation, adhesion, and migration of endothelial and tumor cells in vitro. We also observed an inhibition of triple negative MDA-MB-231 xenograft growth by 75% relative to control when administered intraperitoneally for 27 days at 10 mg/kg. We monitored in vivo the changes in vascular properties throughout the treatment using MRI and found that the vascular volume and permeability surface area product decreased significantly. The treatment also resulted in an increase of caspase-3 activity and in a reduction of microvascular density. The multiple mode of action of this peptide, i.e., anti-angiogenic, and anti-tumorigenic, makes it a viable candidate as a therapeutic agent as a monotherapy or in combination with other compounds. 相似文献
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Grzegorz Gajos Aleksander Siniarski Joanna Natorska Michał Ząbczyk Jakub Siudut Krzysztof Piotr Malinowski Renata Gołębiowska-Wiatrak Paweł Rostoff Anetta Undas 《Cardiovascular diabetology》2018,17(1):146
Background
Little is known about factors that affect the composition of contracted blood clots in specific diseases. We investigated the content of polyhedral erythrocytes (polyhedrocytes) formed in blood clots and its determinants in type 2 diabetes (T2D) patients.Methods
In 97 patients with long-standing T2D [median HbA1c, 6.4% (interquartile range 5.9–7.8)], we measured in vitro the composition of blood clots, including a clot area covered by polyhedrocytes using scanning electron microscopy and the erythrocyte compression index (ECI), defined as a ratio of the mean polyhedrocyte area to the mean native erythrocyte area. Moreover, plasma fibrin clot permeability (Ks), clot lysis time (CLT), thrombin generation, oxidative stress [total protein carbonyl (total PC), total antioxidant capacity and thiobarbituric acid reactive substances (TBARS)], and platelet activation markers were determined. The impact of glucose concentration on polyhedrocytes formation was assessed in vitro.Results
Polyhedrocytes content in contracted clots was positively correlated with glucose (r?=?0.24, p?=?0.028), glycated hemoglobin (r?=?0.40, p?=?0.024), total cholesterol (r?=?0.22, p?=?0.044), TBARS (r?=?0.60, p?=?0.0027), P-selectin (r?=?0.54, p?=?0.0078) and platelet factor-4, PF4 (r?=?0.59, p?=?0.0032), but not with thrombin generation, platelet count, Ks or CLT. Patients who formed more polyhedrocytes (≥?10th percentile) (n?=?83, 85.6%) had higher glucose (+?15.7%, p?=?0.018), fibrinogen (+?16.6%, p?=?0.004), lower red blood cell distribution width (RDW, ??8.8%, p?=?0.034), reduced plasma clot density (??21.8% Ks, p?=?0.011) and impaired fibrinolysis (+?6.5% CLT, p?=?0.037) when compared to patients with lesser amount of polyhedrocytes (<?10th percentile). ECI and the content of polyhedrocytes were strongly associated with total PC (r?=?0.79, p?=?0.036 and r?=?0.67, p?=?0.0004, respectively). In vitro an increase of glucose concentration by 10 mmol/L was associated with 94% higher polyhedrocytes content (p?=?0.033) when compared to the baseline (7.1 mM). After adjustment for age, sex and fibrinogen, multiple regression analysis showed that RDW was the only independent predictor of polyhedrocytes content in T2D (OR?=?0.61, 95% CI 0.39–0.92).Conclusions
Poor glycemic control, together with enhanced platelet activation and oxidative stress, increase the content of polyhedrocytes in blood clots generated in T2D patients.104.
Human expression patterns: qualitative and quantitative analysis of thrombospondin‐1 under physiological and pathological conditions 下载免费PDF全文
Chen Zhao Jeffrey S. Isenberg Aleksander S. Popel 《Journal of cellular and molecular medicine》2018,22(4):2086-2097
Thrombospondin‐1 (TSP‐1), a matricellular protein and one of the first endogenous anti‐angiogenic molecules identified, has long been considered a potent modulator of human diseases. While the therapeutic effect of TSP‐1 to suppress cancer was investigated in both research and clinical settings, the mechanisms of how TSP‐1 is regulated in cancer remain elusive, and the scientific answers to the question of whether TSP‐1 expressions can be utilized as diagnostic or prognostic marker for patients with cancer are largely inconsistent. Moreover, TSP‐1 plays crucial functions in angiogenesis, inflammation and tissue remodelling, which are essential biological processes in the progression of many cardiovascular diseases, and therefore, its dysregulated expressions in such conditions may have therapeutic significance. Herein, we critically analysed the literature pertaining to TSP‐1 expression in circulating blood and pathological tissues in various types of cancer as well as cardiovascular and inflammation‐related diseases in humans. We compare the secretion rates of TSP‐1 by different cancer and non‐cancer cells and discuss the potential connection between the expression changes of TSP‐1 and vascular endothelial growth factor (VEGF) observed in patients with cancer. Moreover, the pattern and emerging significance of TSP‐1 profiles in cardiovascular disease, such as peripheral arterial disease, diabetes and other related non‐cancer disorders, are highlighted. The analysis of published TSP‐1 data presented in this review may have implications for the future exploration of novel TSP‐1‐based treatment strategies for cancer and cardiovascular‐related diseases. 相似文献
105.
Recent developments in high-throughput genotyping technologies have revealed the existence of several new classes of RNA that do not encode proteins but serve other cellular roles. To date, these non-coding RNAs (ncRNAs) have been shown to modulate both gene expression and genome remodeling, thus contributing to the control of both normal and disease-related cellular processes. The attraction of this research topic can be seen in the increasing number of submissions on ncRNAs to molecular biology journals, including Cellular Molecular Biology Letters (CMBL). As researchers attempt to deepen the understanding of the role of ncRNAs in cell biology, it is worth discussing the broader importance of this research. 相似文献
106.
The Xerobranching Response Represses Lateral Root Formation When Roots Are Not in Contact with Water
Beata Orman-Ligeza Emily C. Morris Boris Parizot Tristan Lavigne Aurelie Babé Aleksander Ligeza Stephanie Klein Craig Sturrock Wei Xuan Ondřey Novák Karin Ljung Maria A. Fernandez Pedro L. Rodriguez Ian C. Dodd Ive De Smet Francois Chaumont Henri Batoko Claire Périlleux Xavier Draye 《Current biology : CB》2018,28(19):3165-3173.e5
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Osman Achmatowicz Anna Banaszek Marek Chmielewski Aleksander Zamojski Wojciech Lobodzinski 《Carbohydrate research》1974,36(1):13-22
The conformational equilibrium (°H1 ?1H°) has been established for 26 diastereoisomeric methyl 3,4-dideoxy-DL-glyc-3-enopyranosides on the basis of the coupling constant J1,2. The position of equilibrium depends on the interplay of steric and polar factors. The concept of the allylic effect is useful in explaining some conformational phenomena. 相似文献
110.
Karen McLuskey Aleksander W. Roszak Yanshi Zhu Neil W. Isaacs 《European biophysics journal : EBJ》2010,39(5):723-755
Integral membrane proteins are involved in a wide range of essential biological functions and the determination of their three-dimensional
structures plays a central role in understanding their function. This review focuses on the structures of one class of integral
membrane proteins: the functionally diverse all-alpha type membrane proteins. It gives an overview of all the structures determined
by X-ray crystallography, describing each system and structure in turn. It shows that the structures of all-alpha type membrane
proteins have made valuable contributions to understanding structure–function relationships in membrane proteins. These range
from the first insights into the function of exciting individual proteins to an in-depth knowledge of protein function from
entire biological systems. 相似文献