Structure–property relationships of a biopolymer network: The eggshell membrane

The eggshell membrane (ESM) is a biopolymer network that may have potential applications in biomedicine, but it also may reveal important details regarding the behaviour of biopolymer networks. In this paper, we have studied the mechanical and morphological properties of the ESM in order to reveal important structure–property relationships. Light optical microscopy and atomic force microscopy were used to assess the morphology of the ESM. The mechanical properties of membranes and individual fibres were studied by means of tensile tests and nanoindentation tests, respectively. The mechanical behaviour of ESM networks in different environmental conditions showed a non-linear and a linear regime. As for elastomers and other biopolymer systems, the non-linear regime was modelled by the Mooney–Rivlin relation. The Young’s modulus in the linear regime of the network was related to the Young’s modulus of the individual fibres using Gibson and Ashby analysis for cellular solids. The results of morphological characterization were used to relate the properties of individual fibres to the properties of the whole networks. This enabled us to predict the macroscopical properties of the network based on the properties of the individual fibres. It was found that the ESM networks behaved as both Mooney–Rivlin and Hookean materials in different environmental conditions. This study helps elucidate the properties of the biopolymer networks found in nature and describes important mechanical properties for the use of the ESM as a biomaterial.     

Lactoferrin: a multifunctional immunoregulatory protein?

Various immunoregulatory and anti-infective roles have been proposed for lactoferrin, the iron-binding protein present in external secretions and neutrophil secondary granules. A recent meeting¹ updated current knowledge of the structure and function of this unusual protein.     

Structure–function relationships and source-to-ground distance in electrospun polycaprolactone

The strength of electrospun scaffolds has direct relevance to their function within tissue engineering. We characterized the effects of source-to-ground distance on the mechanical properties of electrospun poly(ε-caprolactone) (PCL). Source-to-ground distances of 10, 15 and 20 cm, solids concentrations of 12 and 18 wt.% and mandrel rotation surface speeds of 0–12 m s^?1 were utilized. Tensile tests evaluated elastic modulus, tensile strength and elongation at failure. Scanning electron microscopy provided morphology and quantified fiber alignment. Increased source-to-ground distance yielded a microstructure allowing greater fiber rearrangement under load, tripling the observed tensile strength. Increases in rotational speed generally increased fiber alignment and strength at high but not low to moderate speeds. As fiber is quickly pulled out of a comparatively gentle falling process, collision with neighboring fibers moving at different speeds and in different directions can occur. The source-to-ground distance influences these collisions and thus has critical implications for microstructure and biocompatibility. In larger diameter (18 wt.% PCL), heavily point-bonded fibers (produced using a shorter, 10 cm source-to-ground distance), elongation at failure in the aligned direction increases dramatically due to severe localized necking. These specimens show only half of the tensile strength (from 2.6 to 4.5 MPa) and a dramatic increase (from 94% to 503%) in elongation at failure vs. a longer 20 cm source-to-ground distance. Strains of several hundred per cent are accompanied by periodic necking of large-diameter fibers in which microstructural failure appears to occur in a sequential manner involving an equilibrium between localized strain in the tensile direction and anisotropic point bonding that locally resists strain.     

Cardiac myosin-binding protein C: hypertrophic cardiomyopathy mutations and structure–function relationships

Cardiac myosin-binding protein C (cMyBP-C) research has been characterized by two waves. Initial interest was piqued by its discovery in 1973 as a contaminant of myosin preparations from skeletal muscle. The second wave started in 1995 by the discovery that mutations in the gene encoding cMyBP-C cause hypertrophic cardiomyopathy (HCM). In this review, we will address what is known of cMyBP-C's role as a regulator of contraction as well as its role in HCM.     

Controllable inhibition of cellular uptake of oxidized low-density lipoprotein: Structure–function relationships for nanoscale amphiphilic polymers

A family of anionic nanoscale polymers based on amphiphilic macromolecules (AMs) was developed for controlled inhibition of highly oxidized low-density lipoprotein (hoxLDL) uptake by inflammatory macrophage cells, a process that triggers the escalation of a chronic arterial disease called atherosclerosis. The basic AM structure is composed of a hydrophobic portion formed from a mucic acid sugar backbone modified at the four hydroxyls with lauroyl groups conjugated to hydrophilic poly(ethylene glycol) (PEG). The AM structure–activity relationships were probed by synthesizing AMs with six key variables: length of the PEG chain, carboxylic acid location, type of anionic charge, number of anionic charges, rotational motion of the anionic group, and PEG architecture. All AM structures were confirmed by nuclear magnetic resonance spectroscopy and their ability to inhibit hoxLDL uptake in THP-1 human macrophage cells was compared in the absence and presence of serum. We report that AMs with one, rotationally restricted carboxylic acid within the hydrophobic portion of the polymer was sufficient to yield the most effective AM for inhibiting hoxLDL internalization by THP-1 human macrophage cells under serum-containing conditions. Further, increasing the number of charges and altering the PEG architecture in an effort to increase serum stabilization did not significantly impair the ability of AMs to inhibit hoxLDL internalization, suggesting that selected modifications to the AMs could potentially promote multifunctional characteristics of these nanoscale macromolecules.     

Structure–function relationships of inhibition of mosquito cytochrome P450 enzymes by flavonoids of Andrographis paniculata

The cytochrome P450 monooxygenases are known to play a major role in pyrethroid resistance, by means of increased rate of insecticide detoxification as a result of their overexpression. Inhibition of detoxification enzymes may help disrupting insect detoxifying defense system. The Anopheles minimus CYP6AA3 and CYP6P7 have shown pyrethroid degradation activity and been implicated in pyrethroid resistance. In this study inhibition of the extracts and constituents of Andrographis paniculata Nees. leaves and roots was examined against benzyloxyresorufin O-debenzylation (BROD) of CYP6AA3 and CYP6P7. Four purified flavones (5,7,4′-trihydroxyflavone, 5-hydroxy-7,8-dimethoxyflavone, 5-hydroxy-7,8,2′,3′-tetramethoxyflavone, and 5,4′-dihydroxy-7,8,2′,3′-tetramethoxyflavone), one flavanone (5-hydroxy-7,8-dimethoxyflavanone) and a diterpenoid (14-deoxy-11,12-didehydroandrographolide) containing inhibitory effects toward both enzymes were isolated from A. paniculata. Structure–function relationships were observed for modes and kinetics of inhibition among flavones, while diterpenoid and flavanone were inferior to flavones. Docking of flavones onto enzyme homology models reinforced relationships on flavone structures and inhibition modes. Cell-based inhibition assays employing 3-(4,5-dimethylthiazol-2-y-l)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assays revealed that these flavonoids efficiently increased susceptibility of CYP6AA3- and CYP6P7-expressing Spodoptera frugiperda (Sf9) cells to cypermethrin toxicity, due to inhibition effects on mosquito enzymes. Thus synergistic effects on cypermethrin toxicity of A. paniculata compounds as a result of enzyme inhibition could be useful for mosquito vector control and insecticide resistance management in the future.     

Expression and function of transforming growth factor β in melioidosis

Melioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, is an important cause of community-acquired sepsis in Southeast Asia and northern Australia. An important controller of the immune system is the pleiotropic cytokine transforming growth factor β (TGF-β), of which Smad2 and Smad3 are the major signal transducers. In this study, we aimed to characterize TGF-β expression and function in experimental melioidosis. TGF-β expression was determined in 33 patients with culture-proven infection with B. pseudomallei and 30 healthy controls. We found that plasma TGF-β concentrations were strongly elevated during melioidosis. In line with this finding, TGF-β expression in C57BL/6 mice intranasally inoculated with B. pseudomallei was enhanced as well. To assess the role of TGF-β, we inhibited TGF-β using a selective murine TGF-β antibody. Treatment of mice with anti-TGF-β antibody resulted in decreased lung Smad2 phosphorylation. TGF-β blockade appeared to be protective: mice treated with anti-TGF-β antibody and subsequently infected with B. pseudomallei showed diminished bacterial loads. Moreover, less distant organ injury was observed in anti-TGF-β treated mice as shown by reduced blood urea nitrogen (BUN) and aspartate transaminase (AST) values. However, anti-TGF-β treatment did not have an effect on survival. In conclusion, TGF-β is upregulated during B. pseudomallei infection and plays a limited but proinflammatory role during experimental melioidosis.     

Effects of connective tissue growth factor and collagen type Ⅰ scleroderma

Objective: To investigate the effects of connective tissue growth factor(CTGF) and collagen type Ⅰ(COL-I) on the pathogenesis of scleroderma and explore the relationship between the level of COL-I and CTGF. Methods: 12 mice model of scleroderma was established by the injection of Bleomycin. The level of CTGF and COL-I were detected by immunohistochemical method. The relationship was analyzed between CTGF and COL-I level. As control group, 12 healthy mice were selected. Results: The levels of CTGF and COL-I in sclerotic models were higher than in normal controls (P ＜ 0.05). It was found that there was a correlation between the level of CTGF and COL-I. Conclusion: CTGF and COL-I played an important role in the hardening process of the skin lesions of the mice model, which may be involved in the pathogenesis of scleroderma.     

Epidermal growth factor,transforming growth factor-α, and epidermal growth factor receptor content in normal and carcinomatous gastric and colonic tissue

Summary Epidermal growth factor (EGF) and transforming growth factor- (TGF-) are polypeptides which bind to the EGF receptor (EGFr) and may play a role in cell growth and carcinogenesis. Our study investigated the content of EGF, TGF-, and EGFr in tumors of the stomach and the colon in comparison with the sourrounding mucosa. EGF was detected in half of the stomach specimens with concentrations between 1 and 9 ng/g weight irrespective of histology. In the colon no EGF was found in the tumor or normal mucosa. In the stomach normal mucosa contained higher TGF- concentrations (mean 22.4 ng/g) than the tumors (mean 11.8 ng/g), but the difference was not statistically significant because of a wide variation in mucosal values. By contrast, the colon mucosa displayed significantly higher TGF- concentrations than the tumor tissues (33 ng/g versus 12 ng/g; P < 0.01). EGFr content in the gastric mucosa was lower compared to gastric carcinoma (48 fmol/g versus 75 fmol/g) yet not significantly different. In contrast, colorectal tumor specimens disclosed significantly higher concentrations than the mucosal tissues (mean of 155 fmol/g versus 80 fmol/g; P < 0.01). In conclusion, TGF- should not be considered a tumorigenic but a physiological growth factor in the stomach and colon. An elevated EGFr content in colorectal tumors in comparison with the normal mucosa could lead to a growth advantage by an autostimulating mechanism.Abbreviations EGF epidermal growth factor - EGFr epidermal growth factor receptor - TGF- transforming growth factor - ROC receiver operating characteristic Dedicated to Prof. Dr. G. Paumgartner on the occasion of his 60th birthday     

Insulin-like growth factor–1 and risk of late-onset Alzheimer's disease: findings from a family study

Insulin-like growth factor–1 (IGF-1), part of an evolutionary conserved signaling pathway in both mammalian and non-mammalian species, is inferred in neurodegenerative disorders including Alzheimer's disease (AD). A murine model for AD shows that reduced IGF-1 signaling prevents AD-like characteristics. However, variation in serum levels of IGF-1 and risk of AD in humans has yet to be determined. We used a proven family design, comparing middle-aged offspring with and without a parental history of AD. The offspring under study carry an increased risk of AD but do not yet experience cognitive impairment. A total of 206 offspring from 92 families with a parental history of AD were compared with 200 offspring from 97 families without a parental history of AD. Apolipoprotein-E (APOE) genotypes and serum IGF-1 levels were compared in subjects with and without a parental history of AD using linear regression, adjusted for APOE genotype and other possible demographic and clinical confounders. Offspring with a parental history of AD were more likely to be an APOE ε4 allele carrier (46.5% vs. 21%, p = 0.001) than were offspring without such a parental history. Offspring with a parental history of AD had higher IGF-1 levels than subjects without such a history, in both unadjusted and adjusted analyses (18.3 mmol/L vs. 16.7 mmol/L, p = 0.001). In conclusion, higher serum IGF-1 levels in middle age are associated with risk of AD disease in older age, independent of APOE genotype.     

Structure–function–property–design interplay in biopolymers: Spider silk

Spider silks have been a focus of research for almost two decades due to their outstanding mechanical and biophysical properties. Recent advances in genetic engineering have led to the synthesis of recombinant spider silks, thus helping to unravel a fundamental understanding of structure–function–property relationships. The relationships between molecular composition, secondary structures and mechanical properties found in different types of spider silks are described, along with a discussion of artificial spinning of these proteins and their bioapplications, including the role of silks in biomineralization and fabrication of biomaterials with controlled properties.     

Application of concentrated growth factor and epidermal growth factor in the field of oral and maxillofacial soft and hard tissue injury repair北大核心

BACKGROUND: Oral and maxillofacial region is a sensitive part of beauty in appearance, and its damage often involves both soft and hard tissues. Concentrated growth factor and recombinant human epidermal growth factor can promote the repair and regeneration of local soft and hard tissue injury, which has become a new research hotspot in recent years. OBJECTIVE: To review the research progress and application of concentrated growth factor and recombinant human epidermal growth factor in the repair of soft and hard tissue injury in oral and maxillofacial region, and discuss the limitations of current research and the possibility of their combined application in the future. METHODS: The English search terms were “CGF, concentrated growth factor, rhEGF, recombinant human epidermal growth factor, tissue regeneration” and the Chinese search terms were “concentrated growth factor, epidermal growth factor, tissue engineering, tissue regeneration, oral and maxillofacial region”. Relevant articles about concentrated growth factor and recombinant human epidermal growth factor were searched in CNKI and PubMed databases. The retrieval time was from 2011 to 2021. Finally, 63 articles were selected. RESULTS AND CONCLUSION: (1) In this paper, the biological characteristics and sources of concentrated growth factor and recombinant human epidermal growth factor were briefly introduced. The research progress and clinical application status of concentrated growth factor and recombinant human epidermal growth factor in promoting the proliferation and differentiation of stem cells related to the regeneration of soft and hard tissues in oral and maxillofacial regions were emphatically summarized. The limitations of current research and possible application directions in the future were discussed. (2) Concentrated growth factor contains a variety of growth factors and CD34+ cells, which can promote the growth, proliferation, migration and differentiation of a variety of tissue cells, especially stem cells, and play an important role in tissue injury repair. (3) Concentrated growth factor is widely used in implant surgery, autologous tooth transplantation, jaw cyst resection, gingival surgery, debridement and suture, which can relieve pain, reduce inflammation, and improve postoperative bone regeneration effect and aesthetic effect. (4) Recombinant human epidermal growth factor has a great development space in soft tissue and nerve regeneration. It has been proven that recombinant human epidermal growth factor can promote a variety of stem cells to differentiate into neuron-like cells, and also induce adipocytes to differentiate into epidermal cells. Most clinical studies suggest that recombinant human epidermal growth factor can promote healing of oral ulcers and reduce scar formation. (5) “Concentrated growth factor + recombinant human epidermal growth factor” combined with adipose-derived stem cells and other stem cells that can be easily obtained have the possibility of directional formation of oral and maxillofacial soft and hard tissue. In the future, it may fill the deep oral and maxillofacial tissue defects caused by trauma, tumor resection, and promote the repair and regeneration of damaged nerves. (6) Trying to use “concentrated growth factor + recombinant human epidermal growth factor” for refractory oral ulcers, periodontal surgery, dental implants, oral and maxillofacial trauma surgery is also a new way to improve oral and maxillofacial function and appearance. Collagen sponge and chitosan membrane may be used as carriers of “concentrated growth factor + recombinant human epidermal growth factor” to facilitate shaping and prolong the action time of the composite. © 2023, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

The interplay between nanostructured carbon-grafted chitosan scaffolds and protein adsorption on the cellular response of osteoblasts: Structure–function property relationship

The rapid adsorption of proteins occurs during the early stages of biomedical device implantation into physiological systems. In this regard, the adsorption of proteins is a strong function of the nature of a biomedical device, which ultimately governs the biological functions. The objective of this study was to elucidate the interplay between nanostructured carbon-modified (graphene oxide and single-walled carbon nanohorn) chitosan scaffolds and consequent protein adsorption and biological function (osteoblast function). We compare and contrast the footprint of protein adsorption on unmodified chitosan and nanostructured carbon-modified chitosan. A comparative analysis of cell–substrate interactions using an osteoblast cell line (MC3T3-E1) implied that biological functions were significantly enhanced in the presence of nanostructured carbon, compared with unmodified chitosan. The difference in their respective behaviors is related to the degree and topography of protein adsorption on the scaffolds. Furthermore, there was a synergistic effect of nanostructured carbon and protein adsorption in terms of favorably modulating biological functions, including cell attachment, proliferation and viability, with the effect being greater on nanostructured carbon-modified scaffolds. The study also underscores that protein adsorption is favored in nanostructured carbon-modified scaffolds such that bioactivity and biological function are promoted.     

Localization of connective tissue growth factor (CTGF) and transforming growth factor beta-2 (TGF-β2) during eye development of four species of birds

Connective tissue growth factor (CTGF) and transforming growth factor (TGF-β2) have essential roles for structure, function, growth, and production of extracellular matrix during eye development. The current study aim was to examine the localization of CTGF and TGF-β2 by immunohistochemical labeling during eye development in four different habitat species of Egyptian birds i.e. chicken (Gallus gallus domesticus), duck(Cairina moschata), quail (Coturnix coturnix), and egret (Bubulcus ibis). Fertilized eggs were obtained to access pre-and post-hatching stages of developing eye. CTGF and TGF-β2 were detected in the inner non-pigmented epithelium layer of ciliary body during eye development of studied birds. Moreover, CTGF was well expressed in the developing sclera, but not expressed in the developing retina. On the contrary, expression of TGF-β2 was detected in the developing retina but was not detected in the developing sclera. The pattern of expression and distribution of CTGF and TGF-β2 in ciliary body, retina and sclera concluded the important cellular function of these growth factors during eye development of studied birds.