Biological Designer Self-Assembling Peptide Nanofiber Scaffolds Significantly Enhance Osteoblast Proliferation, Differentiation and 3-D Migration

A class of self-assembling peptide nanofiber scaffolds has been shown to be an excellent biological material for 3-dimension cell culture and stimulating cell migration into the scaffold, as well as for repairing tissue defects in animals. We report here the development of several peptide nanofiber scaffolds designed specifically for osteoblasts. We designed one of the pure self-assembling peptide scaffolds RADA16-I through direct coupling to short biologically active motifs. The motifs included osteogenic growth peptide ALK (ALKRQGRTLYGF) bone-cell secreted-signal peptide, osteopontin cell adhesion motif DGR (DGRGDSVAYG) and 2-unit RGD binding sequence PGR (PRGDSGYRGDS). We made the new peptide scaffolds by mixing the pure RAD16 and designer-peptide solutions, and we examined the molecular integration of the mixed nanofiber scaffolds using AFM. Compared to pure RAD16 scaffold, we found that these designer peptide scaffolds significantly promoted mouse pre-osteoblast MC3T3-E1 cell proliferation. Moreover, alkaline phosphatase (ALP) activity and osteocalcin secretion, which are early and late markers for osteoblastic differentiation, were also significantly increased. We demonstrated that the designer, self-assembling peptide scaffolds promoted the proliferation and osteogenic differentiation of MC3T3-E1. Under the identical culture medium condition, confocal images unequivocally demonstrated that the designer PRG peptide scaffold stimulated cell migration into the 3-D scaffold. Our results suggest that these designer peptide scaffolds may be very useful for promoting bone tissue regeneration

High Tumour Cannabinoid CB1 Receptor Immunoreactivity Negatively Impacts Disease-Specific Survival in Stage II Microsatellite Stable Colorectal Cancer

BACKGROUND: There is good evidence in the literature that the cannabinoid system is disturbed in colorectal cancer. In the present study, we have investigated whether CB(1) receptor immunoreactive intensity (CB(1)IR intensity) is associated with disease severity and outcome. METHODOLOGY/PRINCIPAL FINDINGS: CB(1)IR was assessed in formalin-fixed, paraffin-embedded specimens collected with a consecutive intent during primary tumour surgical resection from a series of cases diagnosed with colorectal cancer. Tumour centre (n = 483) and invasive front (n = 486) CB(1)IR was scored from 0 (absent) to 3 (intense staining) and the data was analysed as a median split i.e. CB(1)IR <2 and ≥2. In microsatellite stable, but not microsatellite instable tumours (as adjudged on the basis of immunohistochemical determination of four mismatch repair proteins), there was a significant positive association of the tumour grade with the CB(1)IR intensity. The difference between the microsatellite stable and instable tumours for this association of CB(1)IR was related to the CpG island methylation status of the cases. Cox proportional hazards regression analyses indicated a significant contribution of CB(1)IR to disease-specific survival in the microsatellite stable tumours when adjusting for tumour stage. For the cases with stage II microsatellite stable tumours, there was a significant effect of both tumour centre and front CB(1)IR upon disease specific survival. The 5 year probabilities of event-free survival were: 85±5 and 66±8%; tumour interior, 86±4% and 63±8% for the CB(1)IR<2 and CB(1)IR≥2 groups, respectively. CONCLUSIONS/SIGNIFICANCE: The level of CB(1) receptor expression in colorectal cancer is associated with the tumour grade in a manner dependent upon the degree of CpG hypermethylation. A high CB(1)IR is indicative of a poorer prognosis in stage II microsatellite stable tumour patients

A Critical Review on the Structural Health Monitoring Methods of the Composite Wind Turbine Blades

With increasing turbine size, monitoring of blades becomes increasingly im-portant, in order to prevent catastrophic damages and unnecessary mainte-nance, minimize the downtime and labor cost and improving the safety is-sues and reliability. The present work provides a review and classification of various structural health monitoring (SHM) methods as strain measurement utilizing optical fiber sensors and Fiber Bragg Gratings (FBG’s), active/ pas-sive acoustic emission method, vibration‒based method, thermal imaging method and ultrasonic methods, based on the recent investigations and prom-ising novel techniques. Since accuracy, comprehensiveness and cost-effectiveness are the fundamental parameters in selecting the SHM method, a systematically summarized investigation encompassing methods capabilities/ limitations and sensors types, is needed. Furthermore, the damages which are included in the present work are fiber breakage, matrix cracking, delamina-tion, fiber debonding, crack opening at leading/ trailing edge and ice accre-tion. Taking into account the types of the sensors relevant to different SHM methods, the advantages/ capabilities and disadvantages/ limitations of repre-sented methods are nominated and analyzed

The role of peptides in bone healing and regeneration: A systematic review

Background: Bone tissue engineering and the research surrounding peptides has expanded significantly over the last few decades. Several peptides have been shown to support and stimulate the bone healing response and have been proposed as therapeutic vehicles for clinical use. The aim of this comprehensive review is to present the clinical and experimental studies analysing the potential role of peptides for bone healing and bone regeneration. Methods: A systematic review according to PRISMA guidelines was conducted. Articles presenting peptides capable of exerting an upregulatory effect on osteoprogenitor cells and bone healing were included in the study. Results: Based on the available literature, a significant amount of experimental in vitro and in vivo evidence exists. Several peptides were found to upregulate the bone healing response in experimental models and could act as potential candidates for future clinical applications. However, from the available peptides that reached the level of clinical trials, the presented results are limited. Conclusion: Further research is desirable to shed more light into the processes governing the osteoprogenitor cellular responses. With further advances in the field of biomimetic materials and scaffolds, new treatment modalities for bone repair will emerge

Diabetic retinopathy is associated with oxidative stress and mitigation of gene expression of antioxidant enzymes

Mohamed Fath El-Bab,1,4 Nashaat S Zaki,2,5 Moaz A Mojaddidi,1 Maan AL-Barry,2 Hesham A El-Beshbishy3,6 1Department of Physiology, Taibah University, Almadinah, Kingdom of Saudi Arabia; 2Department of Ophthalmology, College of Medicine, Taibah University, Almadinah, Kingdom of Saudi Arabia; 3Department of Medical Laboratories Technology, Faculty of Applied Medical Sciences, Taibah University, Almadinah, Kingdom of Saudi Arabia; 4Department of Physiology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; 5Department of Ophthalmology, Faculty of Medicine, Mansoura University, Mansoura, Egypt; 6Biochemistry Department, Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo, Egypt Abstract: Type 2 diabetes is a metabolic disease associated with serious complications, including diabetic retinopathy (DR). The authors&#39; main aim was to investigate biochemical parameters and the oxidative stress associated with the type 2 DR patients and to study gene expression of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) among patients with DR [DR(+)] compared with a control nondiabetic group. In all, 67 patients with DR included in this study were diabetic for more than 10 years. Among them, 22 patients were DR(+), and 45 patients did not have DR [DR(-)]. The subjects&#39; age range was 14 years to 80 years old with diabetes duration range between 2 and 45 years. Body mass index (BMI) was 31.43 &plusmn; 5.94 and 32.33 &plusmn; 6.54, systolic blood pressure was 117.15 &plusmn; 18.16 mmHg and 126.15 &plusmn; 20.26 mmHg, diastolic blood pressure was 81.11 &plusmn; 10.55 mmHg and 82.77 &plusmn; 10.85 mmHg, HbA1c was 7.2 &plusmn; 1.1 and 8.19 &plusmn; 1.95, serum total cholesterol was 6.61 &plusmn; 1.11 and 4.11 &plusmn; 0.31, serum triglycerides were 3.52 &plusmn; 0.89 and 3.42 &plusmn; 0.79, serum low-density lipoprotein (LDL) was 2.12 &plusmn; 0.10 and 2.42 &plusmn; 0.15, high-density lipoprotein (HDL) was 2.66 &plusmn; 0.30 and 2.55 &plusmn; 0.21, SOD was 3.12 &plusmn; 0.87 and 1.53 &plusmn; 0.14, GPx was 11.14 &plusmn; 2.21 and 8.2 &plusmn; 1.84, CAT was 26.43 &plusmn; 3.34 and 9.60 &plusmn; 2.14, for DR(-) and DR(+) patients, respectively. SOD, GPx and CAT polymerase chain reaction (PCR) products of the DR(+) patients revealed the diminished expression of CAT gene followed by GPx and SOD genes. All were significant compared with the normal controls, P < 0.05. Linear regression analysis revealed a strong significant positive correlation between the retinopathy grade and the diastolic blood pressure, diabetes duration, hemoglobin A1c (HA1c)%, and fasting blood glucose (P < 0.001). A marginally significant positive correlation between the retinopathy grade and LDL-cholesterol was observed (P < 0.05), and a significant negative correlation between the retinopathy grade and total cholesterol was observed (P < 0.05). Poor glycemic control and alteration in mRNA gene expression of antioxidant enzymes are strongly associated with development of DR and the regular screening is mandatory for early detection and treatment. Keywords: diabetic retinopathy, antioxidant enzymes, gene expressio

P63 expression in papillary cystadenoma and mucoepidermoid carcinoma of minor salivary glands

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Objective. The aim of this study was to investigate the expression of p63 protein in mucoepidermoid carcinoma and papillary cystadenoma of the salivary glands, and to evaluate the usefulness of this protein in distinguishing these tumors. Study Design. Immunoexpression of p63 protein was studied and quantified in 9 formalin-fixed paraffin-embedded mucous retention cysts, 4 papillary cystadenomas, and 19 low-grade and 9 high-grade mucoepidermoid carcinomas. Results. All cases were positive for p63 immunoexpression; however, it was observed that p63 labeling in mucous retention cysts and papillary cystadenomas was limited to the basal layers of the cystic spaces, whereas in low-grade mucoepidermoid carcinomas, positive nuclear staining was also found diffusely in the suprabasal layers. Mucoepidermoid carcinoma presented increased immunoexpression of p63 compared with the other groups. Conclusions. P63 immunohistochemical expression pattern can be helpful in distinguishing low-grade mucoepidermoid carcinoma from papillary cystadenoma of the salivary glands. (Oral Surg Oral Med Oral Pathol Oral Radiol 2013;115:79-86)11517986Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [2009/53839-2