I'm a PhD student in Food Science, mainly working on bioactive proteins and peptides :)
The Potential Benefits of Egg White Protein on Osteoporosis Prevention and Bone Health Management
Osteoporosis is a serious public health concern, affecting more than 200 million people worldwide, whose incidence is more than the combination of heart attack, stroke and breast cancer. It has been considered as the most serious health issue, especially the world has entered into an era of aging society. An estimated 1/2 women and 1/5 men will develop osteoporosis during their lifetime. Unfortunately, there is no efficient strategy to prevent and treat osteoporosis at the moment. Synthetic antiresorptive drugs are the main pharmacological strategies for osteoporosis patients; however, these agents are associated with severe side effects and limited in their ability to restore bone mass. Therefore, it is imperative to develop alternate treatments. Nutrition is an important modifiable component of bone health and plays a major role in the development and maintenance of bone structure. Thus, there is an increasing interest in using natural nutritional components as alternatives for osteoporosis prevention and treatment. Ovotransferrin, an egg white protein, shows the potential to be used as a new therapeutic approach due to its ability in promoting bone formation as well as inhibiting bone resorption. In my research, the potential of ovotransferrin in preventing osteoporosis and enhancing bone health will be studied along with the underlying mechanisms, which will help to develop new techniques to bone health management, as well as to open up new applications of egg proteins for egg industry.
Abstract: Osteoporosis is defined as a progressive systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Although bone mass and quality is mainly determined genetically, many other factors, including lifestyle and nutrition also have an impact on bone health. It has been suggested that dietary protein intake may be a risk factor for osteoporosis, and high-protein diets are associated with increased bone loss. Many scientists have examined the relationship between types of protein and urinary calcium excretion, and found that although animal protein was associated with increased urinary calcium excretion, soy protein was not. There is sufficient evidence suggesting soy isoflavones may have potential benefits for bone. Soy protein with naturally occurring phytoestrogens, mainly isoflavones protect against bone loss and synthetic soy ipriflavone in some studies has been shown to favorably affect, but a cause and effect relationship has not been established between the consumption of ipriflavone and maintenance of bone mineral density in post-menopausal women. Therefore it is too early to recommend it as a supplement for this group of women.
Pub.: 29 Oct '10, Pinned: 05 Jul '17
Abstract: Protein-based composites have always been desirable biomaterials as they can be fabricated into a wide range of biomaterials with tunable properties, including modulation of mechanical properties and control of cell responses. Both egg white protein (EW) and silk fibroin (SF) are biocompatible, biodegradable, non-toxic and naturally abundant biopolymers. In order to obtain biocompatible composite films with tunable performance, EW and SF were blended at various ratios. Raising the SF ratio in the composite films significantly increased breaking strength, but impaired flexibility. Conversely, increasing the EW ratio remarkably enhanced elasticity of the composite films. Furthermore, the biological assays based on endothelial cells showed that the incorporation of EW promoted cell viability. These make them potential materials with controllable mechanical property and enhanced bioactivity, providing useful options for the fabrication of tissue engineering scaffolds.
Pub.: 21 Jun '17, Pinned: 05 Jul '17
Abstract: Osteoporosis is one of the systemic features of COPD. A correlation between the emphysema phenotype of COPD and reduced bone mineral density (BMD) is suggested by some studies, however, the mechanisms underlying this relationship are unclear. Experimental studies indicate that IL-1β, IL-6 and TNF-α may play important roles in the etiology of both osteoporosis and emphysema. The OPG/RANK/RANKL system is an important regulator of bone metabolism, and participates in the development of post-menopausal osteoporosis. Whether the OPG/RANK/RANKL pathway is involved in the pathogenesis of osteoporosis in COPD has not been studied.Eighty male patients (current or former smokers) completed a chest CT scan, pulmonary function test, dual x-ray absorptiometry measurements and questionnaires. Among these subjects, thirty patients with normal BMD and thirty patients with low BMD were selected randomly for measurement of IL-1β, IL-6, TNF-α (flow cytometry) and OPG/RANK/RANKL (ELISA). Twenty age-matched healthy volunteers were recruited as controls.Among these eighty patients, thirty-six had normal BMD and forty-four had low BMD. Age, BMI and CAT score showed significant differences between these two COPD groups (p < 0.05). The low-attenuation area (LAA%) in the lungs of COPD patients was negatively correlated with lumbar vertebral BMD (r = 0.741; p < 0.0001). Forward logistic regression analysis showed that only LAA% (p = 0.005) and BMI (p = 0.009) were selected as explanatory variables. The level of IL-1β was significantly higher in the COPD patients as compared to the normal controls (p < 0.05), but the difference between the two COPD groups did not reach significance. The levels of IL-6 and TNF-α among the three groups were significantly different (p < 0.05). The level of RANKL and the RANKL/OPG ratio were significantly higher in COPD patients with low BMD compared to those with normal BMD and the normal controls (p < 0.05), and correlated negatively with lumbar vertebral BMD, but positively with LAA%.Radiographic emphysema is correlated with low BMD in current and former smokers with COPD. IL-1β, IL-6, TNF-α, and the osteoporosis-related protein system OPG/RANK/RANKL may have some synergetic effects on emphysema and bone loss in COPD.
Pub.: 20 Dec '11, Pinned: 05 Jul '17
Abstract: Osteoporotic fracture is one of the most common health risks and aggravates the quality of life among postmenopausal women worldwide. In this study, osteoporosis-associated protein biomarkers were identified from urine of osteoporotic female Sprague-Dawley rats developed by ovariectomy.Four months after the operation, the bone mineral density of the femur of ovariectomized rats was significantly lowered in comparison with that of the sham operated rats. The protein profiles of the urine samples collected from the sham, ovariectomized (OVX) and 2 month-old non-operated (Young) rats were compared by 2-D gel and MS spectrometry.Proteins consistently expressed between Young and sham but differentially expressed in OVX rats were selected and identified. One down-regulated 21 kDa protein, superoxide dismutase (SOD), and 1 up-regulated 53-54 kDa protein, alph-1-antitrypsin (A1AT), were selected from urine of the ovariectomized rats by 2-D gel analysis. Further, a total of 30 with 19 up-regulated and 11-down-regulated proteins were selected by LC-MS analysis with more than 2-fold differences in spectral counts. The fact that SOD and A1AT are also listed in the 30 differential proteins suggests that our biomarker isolation procedure suitably represents osteoporosis-associated proteins in urine.Supporting the facts, the differential expressions of SOD and A1AT in urine could be validated by Western blotting. These urinary osteoporosis-associated proteins have high potentials to become candidates for non-invasive diagnosis of osteoporosis from urine.
Pub.: 06 Jun '17, Pinned: 05 Jul '17
Abstract: One of the causes of iron deficiency in human is poor absorption of non-heme iron from the diet. While proteins from meats have been reported in the literature to enhance the absorption of non-heme iron, other proteins, such as those from egg, are known to inhibit iron absorption. The objective of this study is to investigate non-heme iron binding property of egg white proteins hydrolyzed using pepsin and a combination of bacterial/fungal proteases. The iron bioavailability of non-heme iron, in the presence of egg white (EW) hydrolysates, was evaluated in vitro using a tissues culture model system - rat intestinal epithelial cells (IEC-6). In the first treatment condition, EW was digested in the presence of ferrous gluconate (FeGluc), producing a peptide-FeGluc complex. In the second treatment, EW was digested in the absence of FeGluc followed by the addition of the non-heme iron. In both treatments, the resulting EW hydrolysates were further separated into > 0.1–0.5 kDa and > 6–8 kDa peptide fractions using dialysis. The hydrolysate and FeGluc complex or mixtures were applied to the IEC-6 cells and iron absorption was measured after 2 h or 16 h. Results showed that the peptide-FeGluc complex digested with a combined proteases from Bacillus licheniformis (SDAY) and from Aspergillus melluss (PP) increased the in vitro iron-binding property but did not enhance iron uptake by the in IEC-6 cells (p < 0.05). Peptide-FeGluc complex digested with pepsin alone (> 0.1–0.5 kDa) resulted in significantly higher iron uptake in IEC-6 cells compared with the higher molecular weight complex (> 6–8 kDa) produced using the same hydrolysis treatment. Similarly, enhanced iron uptake was observed with the complexes produced with the combined SDAY and PP enzymatic treatments (> 0.1–0.5 kDa and > 6–8 kDa) (p < 0.05). On the other hand, the enhanced iron absorption effect was not observed when pre-hydrolyzed free peptides were added to FeGluc. Overall, this study suggests that low molecular weight fractions of egg white protein hydrolysates can enhance the bioavailability of non-heme iron. Furthermore, the method by which the egg white proteins are being prepared, i.e., in the presence or absence of FeGluc, can affect the bioavailability of the non-heme iron.
Pub.: 28 Feb '17, Pinned: 05 Jul '17
Abstract: Angiotensin converting enzyme (ACE) inhibitory peptides from egg have demonstrated reduction of blood pressure (BP) in vivo. In this study we evaluated the effects of egg white hydrolysate (EWH) prepared by thermolysin and pepsin in spontaneously hypertensive rats (SHRs). Fourteen to sixteen week old SHRs were implanted with telemetry devices. After recovery, the rats were divided randomly into three groups: untreated, EWH low dose (250 mg/kg BW), and EWH high dose (1000 mg/kg BW) for 12 days. BP showed a significant reduction in the EWH high dose group compared to untreated controls. BP reduction was associated with enhanced ex vivo vasodilation reduced oxidative/nitrosative stress, reduced angiotensin converting enzyme and angiotensin II type 1 receptor expression, while enhanced angiotensin II type 2 receptor expression. Circulating level of angiotensin II was unaffected. Thus, EWH exerted anti-hypertensive effects in SHRs through multiple mechanisms of vascular relaxation and RAS modulation.
Pub.: 09 Nov '16, Pinned: 05 Jul '17
Abstract: Despite genome-wide association studies (GWASs) have identified many susceptibility genes for osteoporosis, it still leaves a large part of missing heritability to be discovered. Integrating regulatory information and GWASs could offer new insights into the biological link between the susceptibility SNPs and osteoporosis. We generated five machine learning classifiers with osteoporosis-associated variants and regulatory features data. We gained the optimal classifier and predicted genome-wide SNPs to discover susceptibility regulatory variants. We further utilized Genetic Factors for Osteoporosis Consortium (GEFOS) and three in-house GWASs samples to validate the associations for predicted positive SNPs. The random forest classifier performed best among all machine learning methods with the F1 score of 0.8871. Using the optimized model, we predicted 37,584 candidate SNPs for osteoporosis. According to the meta-analysis results, a list of regulatory variants was significantly associated with osteoporosis after multiple testing corrections and contributed to the expression of known osteoporosis-associated protein-coding genes. In summary, combining GWASs and regulatory elements through machine learning could provide additional information for understanding the mechanism of osteoporosis. The regulatory variants we predicted will provide novel targets for etiology research and treatment of osteoporosis.
Pub.: 22 Jun '17, Pinned: 05 Jul '17
Abstract: Oxidative stress has currently been proposed as a risk factor associated with the development and proression of osteoporosis. In this study, we identify the effect of mangiferin (MAN) on apoptosis and differentiation of osteoblast-like MC3T3-E1 cells insulted by H2O2. We firstly found that MAN can promote cell proliferation of MC3T3-E1 cells in a time- and dose-dependent manner and stimulate the phosphorylation of ERK5. Cells were divided as five groups: control, H2O2 (100 μM, control), H2O2 + MAN (5 μM), H2O2 + MAN (10 μM), and H2O2 + MAN (20 μM). MAN can significantly decrease H2O2-induced apoptosis and elevated ROS level of MC3T3-E1 cells. The expressions of caspase-3, caspase-9 and Bax/Bcl-2 were increased with H2O2 treatment, and MAN can reverse these changes. In addition, Nrf2 and its downstream target effectors (HO1, NQO1) were dramatically attenuated in MC3T3-E cells treatment with H2O2, while MAN can significantly increase the expression of Nrf2, HO1 and NQO1. The expression of ERK5 was down regulated by RNA interference in MC3T3-E1 cells, and we found that MAN (20 μM) pretreatment didn't make remarkable decrease in cell apoptosis or expressions of apoptosis-related proteins in H2O2-insulted siRNA-ERK5 cells. This study indicated that MAN can protect osteoblast against oxidative damage by modulation of ERK5/Nrf2 signaling, which can be new agent for osteoporosis.
Pub.: 04 Jul '17, Pinned: 05 Jul '17
Abstract: Bone mineral density (BMD) is a measure of osteoporosis and is useful in evaluating the risk of fracture. In a genome-wide association study of BMD among 20,100 Icelanders, with follow-up in 10,091 subjects of European and East-Asian descent, we found a new BMD locus that harbours the PTCH1 gene, represented by rs28377268 (freq. 11.4–22.6%) that associates with reduced spine BMD (P=1.0 × 10−11, β=−0.09). We also identified a new spine BMD signal in RSPO3, rs577721086 (freq. 6.8%), that associates with increased spine BMD (P=6.6 × 10−10, β=0.14). Importantly, both variants associate with osteoporotic fractures and affect expression of the PTCH1 and RSPO3 genes that is in line with their influence on BMD and known biological function of these genes. Additional new BMD signals were also found at the AXIN1 and SOST loci and a new lead SNP at the EN1 locus.
Pub.: 06 Jan '16, Pinned: 30 Jun '17
Abstract: Inhibition of the Wnt antagonist sclerostin increases bone mass in patients with osteoporosis and in preclinical animal models. Here we show increased levels of the Wnt antagonist Dickkopf-1 (DKK-1) in animals treated with sclerostin antibody, suggesting a negative feedback mechanism that limits Wnt-driven bone formation. To test our hypothesis that co-inhibition of both factors further increases bone mass, we engineer a first-in-class bispecific antibody with single residue pair mutations in the Fab region to promote efficient and stable cognate light–heavy chain pairing. We demonstrate that dual inhibition of sclerostin and DKK-1 leads to synergistic bone formation in rodents and non-human primates. Furthermore, by targeting distinct facets of fracture healing, the bispecific antibody shows superior bone repair activity compared with monotherapies. This work supports the potential of this agent both for treatment and prevention of fractures and offers a promising therapeutic approach to reduce the burden of low bone mass disorders.
Pub.: 27 May '16, Pinned: 30 Jun '17
Abstract: Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are common inflammatory conditions. The diagnosis of PMR/GCA poses many challenges since there are no specific diagnostic tests. Recent literature emphasizes the ability of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to assess global disease activity in inflammatory diseases. 18F-FDG PET/CT may lead to the diagnosis at an earlier stage than conventional imaging and may also assess response to therapy. With respect to the management of PMR/GCA, there are 3 significant areas of concern as follows: vasculitis process/vascular stiffness, malignancy, and osteoporosis.All patients with suspected PMR/GCR referred to the Rheumatology section of Medicine Department at Svendborg Hospital, Denmark. The 4 separate studies in the current protocol focus on: the association of clinical picture of PMR/GCA with PET findings; the validity of 18F-FDG PET/CT scan for diagnosis of PMR/GCA compared with temporal artery biopsy; the prevalence of newly diagnosed malignancies in patients with PMR/GCA, or PMR-like syndrome, with the focus on diagnostic accuracy of 18F-FDG PET/CT scan compared with conventional workup (ie, chest X-ray/abdominal ultrasound); and the impact of disease process, and also steroid treatment on bone mineral density, body composition, and vasculitis/vascular stiffness in PMR/GCA patients.The study has been approved by the Regional Ethics Committee of the Region of Southern Denmark (identification number: S-20160098) and Danish Data Protection Agency (J.nr 16/40522). Results of the study will be disseminated via publications in peer-reviewed journals, and presentation at national and international conferences.
Pub.: 29 Jun '17, Pinned: 30 Jun '17