scholarly journals Biological Applications of a Chimeric Probe for the Assessment of Galectin-3 Ligands

2007 ◽  
Vol 55 (10) ◽  
pp. 1015-1026 ◽  
Author(s):  
Fabiana H. M. de Melo ◽  
Diego Butera ◽  
Raphael S. Medeiros ◽  
Luciana N. de S. Andrade ◽  
Suely Nonogaki ◽  
...  

β1–6 branching of N-linked oligosaccharides has been correlated with the progression of different cancers. The leukoagglutinins of Phaseolus vulgaris (L-PHA) have been used to study this pattern of glycosylation whose biological significance is incompletely understood. The animal lectin, galectin-3, also binds to structures recognized by L-PHA. To develop a functional tool for the in situ identification of this pattern of glycosylation, human galectin-3 was fused to bacterial alkaline phosphatase (gal3/AP). Gal3/AP recognized both A and B blood group saccharides (B>A) and lactosamine derivatives. Gal3/AP recognition depended at least in part on the N-linked oligosaccharides of different glycoproteins. The presence and distribution of galectin-3 ligands were analyzed in both murine and human normal and tumor samples. Loss of apical expression of galectin-3 ligands was commonly found in carcinomas. Endothelial and inflammatory cells were enriched in galectin-3 ligands as compared with tumor cells; thus, gal3/AP is a suitable tool for studying tumor micro-environments. Comparative analysis of both gal3/AP and L-PHA binding patterns indicated that although similar, these patterns are not identical. The probe developed was useful for several immunoenzymatic assays and will allow the physiological and clinical significance of the expression pattern of galectin-3 ligands to be established. This manuscript contains online supplemental material at http:/www.jhc.org . Please visit this article online to view these materials. (J Histochem Cytochem 55: 1015–1026, 2007)

2020 ◽  
Vol 154 (2) ◽  
pp. 135-153 ◽  
Author(s):  
Gabriel García Caballero ◽  
Donella Beckwith ◽  
Nadezhda V. Shilova ◽  
Adele Gabba ◽  
Tanja J. Kutzner ◽  
...  

Abstract The concept of biomedical significance of the functional pairing between tissue lectins and their glycoconjugate counterreceptors has reached the mainstream of research on the flow of biological information. A major challenge now is to identify the principles of structure–activity relationships that underlie specificity of recognition and the ensuing post-binding processes. Toward this end, we focus on a distinct feature on the side of the lectin, i.e. its architecture to present the carbohydrate recognition domain (CRD). Working with a multifunctional human lectin, i.e. galectin-3, as model, its CRD is used in protein engineering to build variants with different modular assembly. Hereby, it becomes possible to compare activity features of the natural design, i.e. CRD attached to an N-terminal tail, with those of homo- and heterodimers and the tail-free protein. Thermodynamics of binding disaccharides proved full activity of all proteins at very similar affinity. The following glycan array testing revealed maintained preferential contact formation with N-acetyllactosamine oligomers and histo-blood group ABH epitopes irrespective of variant design. The study of carbohydrate-inhibitable binding of the test panel disclosed up to qualitative cell-type-dependent differences in sections of fixed murine epididymis and especially jejunum. By probing topological aspects of binding, the susceptibility to inhibition by a tetravalent glycocluster was markedly different for the wild-type vs the homodimeric variant proteins. The results teach the salient lesson that protein design matters: the type of CRD presentation can have a profound bearing on whether basically suited oligosaccharides, which for example tested positively in an array, will become binding partners in situ. When lectin-glycoconjugate aggregates (lattices) are formed, their structural organization will depend on this parameter. Further testing (ga)lectin variants will thus be instrumental (i) to define the full range of impact of altering protein assembly and (ii) to explain why certain types of design have been favored during the course of evolution, besides opening biomedical perspectives for potential applications of the novel galectin forms.


Rheumatology ◽  
2020 ◽  
Vol 60 (1) ◽  
pp. 322-332
Author(s):  
Eri Watanabe ◽  
Kazunori Kato ◽  
Takahisa Gono ◽  
Emiko Chiba ◽  
Chihiro Terai ◽  
...  

Abstract Objectives Galectin-3 is involved in various biological activities, including immune activations and fibrosis. Idiopathic inflammatory myopathies (IIMs) are autoimmune diseases of unknown aetiology, often complicated by interstitial lung disease (ILD). The aim of this study was to evaluate the expression of galectin-3 in sera and tissues of patients with IIM and assess the associations of galectin-3 with patient characteristics and disease activity. Results Serum galectin-3 levels were significantly higher in IIM patients than in healthy controls. The serum galectin-3 levels positively correlated with serum levels of inflammatory markers and proinflammatory cytokines/chemokines and the Myositis Intention-to-Treat Activity Index. Stratification analysis revealed that patients with IIM-associated ILD (IIM-ILD) had significantly higher levels of serum galectin-3 than those without IIM-ILD. In addition, patients with acute/subacute interstitial pneumonia had significantly higher levels of serum galectin-3 than those with chronic interstitial pneumonia. Furthermore, serum galectin-3 levels in IIM-ILD patients correlated with the radiological assessments of parenchymal lung involvement and treatment response. Immunohistochemical analysis revealed that galectin-3 was expressed in inflammatory cells of myositis and dermatitis sections, whereas in ILD sections, galectin-3 was expressed in interstitial fibrosis and inflammatory cells. Conclusion Galectin-3 may be involved in the pathogenesis of inflammatory and fibrotic conditions in IIM and can serve as a potential biomarker of disease activity, especially in patients with IIM-ILD.


2005 ◽  
Vol 70 (6) ◽  
pp. 2143-2147 ◽  
Author(s):  
Joanne Dyer ◽  
Steffen Jockusch ◽  
Vojtech Balsanek ◽  
Dalibor Sames ◽  
Nicholas J. Turro

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Ivan Luzardo ◽  
Rocio Campos-Vega ◽  
Elvira Gonzalez de Mejia ◽  
Flavia Loarca

Abstract Objectives The aim of this research was to evaluate the anti-inflammatory properties of an oven-baked nixtamalized corn (Zea mays L.)/cooked common bean (Phaseolus vulgaris L.) chip in a model of chronic colitis in vivo. The hypothesis was that the chip consumption would prevent colon barrier disruption and improve enzymatic biomarkers by the modulation of infiltration and adhesion of inflammatory cells. Methods A 70% corn and 30% bean chip (7030C) was evaluated, using dextran sodium sulfate (DSS, 2% v/v) as chemical inductor of colitis. After 1-week of acclimatization, 36 CD-1 male mice (6–8 weeks age) were randomly divided into 5 groups: G1 (negative control, fed with basal diet, BD, and water); G2 (positive control, BD + DSS), G3 (100 g 7030C/kg body weight, BW/day + BD), G4 (200 g 7030C/kg BW + BD) and G5 (300 g 7030C/kg BW + BS). The G2-G5 groups were administered DSS every other week, during 5-weeks.After the mice were euthanized, BW and disease activity index (DAI) were recorded. Liver, colon, and spleen were collected, weighed and analyzed for histology. Colonic myeloperoxidase (MPO)/fecal b-glucuronidase (GLUC) activities were also quantified, as well as fecal/cecal metabolites. The colonic mRNA expression of inflammation-associated genes was conducted using a gene inflammation profiler array. Results DSS increased DAI up to 2 units, BW loss was 10–17%, and induced colon shortening 10–15%. Compared to G2, G4 exhibited significantly (p < 0.05) lower DAI (0.75 ± 0.01), spleen relative weight (0.003 ± 0.0001) and colon weight/length ratio (0.045 ± 0.008). The histological analysis showed that the chip consumption prevented colonic barrier damage. G4 displayed the lowest MPO and GLUC among all DSS-induced groups (0.004 ± 0.0004 mU/mg colon; 0.44 ± 0.01 mmol/min/g feces, respectively), and the lowest seric content of MCP-1 protein. Amid all the quantified metabolites, the chip consumption significantly reduced the fecal/cecal content of acetic acid, while butyric and propionic increased at the end of the study. Inflammation gene expression was modulated by the chip consumption. Conclusions Our results suggest that the consumption of this chip might alleviate chronic colitis symptoms because of a protective effect in the gut barrier function and the modulation of infiltration of inflammatory cells. Funding Sources The funding received by CONACyT, CONCyTEQ-Mexico and NIFA-USDA-HATCH are appreciated.


2019 ◽  
Vol 7 (6) ◽  
pp. 2511-2519 ◽  
Author(s):  
Celia Garcia-Hernandez ◽  
Allison K. Freese ◽  
Maria L. Rodriguez-Mendez ◽  
Adam K. Wanekaya

We demonstrate an in situ synthesis, stabilization and activity of a nanoparticle-based protein carrier platform via the Layer-by-Layer (LbL) technology.


1956 ◽  
Vol 185 (3) ◽  
pp. 487-494 ◽  
Author(s):  
A. Alella ◽  
F. L. Williams ◽  
C. Bolene-Williams ◽  
L. N. Katz

The relationship (over the normal range) between work, the consumption of oxygen, glucose and lactic acid and the RQ have been studied on the heart in situ in controlled experiments. The following conclusions were reached: a) The correlation found between work and oxygen consumption was imperfect because the behavior of a heart when its work is increased is different as regards oxygen consumption when it is performing pressure-work than when it is performing an equal amount of volume-work. b) The heart rate is an important factor in determining the oxygen consumed by the heart in situ at a given work load. c) The RQ was found to be unrelated to the work level of the heart. It remained relatively constant over the normal range indicating that the nature of the metabolism is probably not altered. d) A low value of ‘efficiency’ was found in this preparation. It does not necessarily indicate an incompetent or insufficient heart. The biological significance of the term, ‘efficiency’ which actually represents merely the ratio of work done to the amount of oxygen consumed, is considered. e) The availability of glucose and lactic acid is not dependent upon the work of the heart; their availability is dependent upon the coronary flow and therefore varies with oxygen consumption. f) The consumption of exogenous glucose by the heart is related to the availability of glucose but not to its arterial blood level. The exogenous glucose consumption of the heart is not related to the cardiac oxygen consumption. g) The consumption of exogenous lactic acid by the heart shows a positive relation to its availability, to its arterial blood level and to the myocardial consumption of oxygen. It appears to be one of the substrates readily used for the work performance of the heart. h) The relative consumption of exogenous glucose and lactic acid by the heart varies with their relative availabilities. i) The significance of these findings is discussed.


Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 389 ◽  
Author(s):  
Akira Hara ◽  
Masayuki Niwa ◽  
Kei Noguchi ◽  
Tomohiro Kanayama ◽  
Ayumi Niwa ◽  
...  

Galectin-3 is a β-galactoside-binding lectin which is important in numerous biological activities in various organs, including cell proliferation, apoptotic regulation, inflammation, fibrosis, and host defense. Galectin-3 is predominantly located in the cytoplasm and expressed on the cell surface, and then often secreted into biological fluids, like serum and urine. It is also released from injured cells and inflammatory cells under various pathological conditions. Many studies have revealed that galectin-3 plays an important role as a diagnostic or prognostic biomarker for certain types of heart disease, kidney disease, viral infection, autoimmune disease, neurodegenerative disorders, and tumor formation. In particular, it has been recognized that galectin-3 is extremely useful for detecting many of these diseases in their early stages. The purpose of this article is to review and summarize the recent literature focusing on the biomarker characteristics and long-term outcome predictions of galectin-3, in not only patients with various types of diseases, but associated animal models.


2014 ◽  
Vol 67 (3) ◽  
pp. 420 ◽  
Author(s):  
Raffaele Colombo ◽  
Kyu Ok Jeon ◽  
Donna M. Huryn ◽  
Matthew G. LaPorte ◽  
Peter Wipf

We discovered a new retro-Mannich reaction of in situ prepared pyrazolopyridines to give pyrazolopyrimidines that have hitherto been underrepresented in the heterocyclic chemistry literature. The isolation of a linear hydrolysis product supports a mechanistic hypothesis for this rearrangement process. In order to establish a broader access and explore potential biological applications for these medicinal chemistry building blocks, we investigated the scope of the reaction and generated small amine- as well as amide-based libraries through reductive aminations and amide couplings, respectively.


2006 ◽  
Vol 33 (3) ◽  
pp. 263-273 ◽  
Author(s):  
SHANKAR ASWANI ◽  
MATTHEW LAUER

Given the frequent socioeconomic, political and concomitant ecological failures of science-driven marine protected area (MPA) programmes, it is now important to design MPAs by integrating natural and social science research more comprehensively. This study shows how indigenous peoples assisted in the design of MPAs by identifying marine substrates and related resident taxa on aerial photos, information which was then incorporated into a geographical information system (GIS) database, along with dive survey data. Two questions were asked: (1) Is indigenous ecological knowledge accurate enough for mapping the benthos and associated taxa? (2) Is such an approach an appropriate way for assisting in the biological and social design of MPAs in Oceania? Conventional quadrat field dive surveys were used to measure the accuracy of substrate identification by local informants and a visual survey was used to test hypotheses formulated from local knowledge regarding the spatial distribution and relative abundance of non-cryptic species within certain benthic habitats. Equivalence rates between indigenous aerial photo interpretations of dominant benthic substrates and in situ dive surveys were 75–85% for a moderately detailed classification scheme of the benthos, which included nine locally-defined abiotic and biotic benthic classes for the MPA seabed. Similarly, the taxa inventory showed a strong correspondence between the qualitative predictions of local fisherfolk and the quantitative analysis of non-cryptic species distribution, including their relative abundance and geophysical locations. Indigenous people's predictions about the presence or absence of fish in different benthic habitats corresponded 77% and 92% of the time (depending on scoring schema) with in situ visual measurements. These results demonstrate how incorporating local knowledge of benthic heterogeneity, existing biological communities, and particular spatio-temporal events of biological significance into a GIS database can corroborate the production of scientifically reliable base resource maps for designing MPAs in an environmentally and culturally sound fashion. This participatory approach was used to design and then establish MPAs in the Roviana and Vonavona region of the Western Solomon Islands. Under appropriate conditions, interdisciplinary work can complement the design of scientific fishery management and biodiversity conservation prescriptions for coastal Oceania.


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