Ovarian cancer treatment remains a challenge and targeting cancer stem cells presents a promising strategy. Niclosamide is an “old” antihelminthic drug that uncouples mitochondria of intestinal parasites. Although recent studies demonstrated that niclosamide could be a potential anticancer agent, its poor water solubility needs to be overcome before further preclinical and clinical investigations can be conducted. Therefore, we evaluated a novel nanosuspension of niclosamide (nano-NI) for its effect against ovarian cancer. Nano-NI effectively inhibited the growth of ovarian cancer cells in which it induced a metabolic shift to glycolysis at a concentration of less than 3 μM in vitro and suppressed tumor growth without obvious toxicity at an oral dose of 100 mg/kg in vivo. In a pharmacokinetic study after oral administration, nano-NI showed rapid absorption (reaching the maximum plasma concentration within 5 min) and improved the bioavailability (the estimated bioavailability for oral nano-NI was 25%). In conclusion, nano-NI has the potential to be a new treatment modality for ovarian cancer and, therefore, further clinical trials are warranted.
OBJECTIVES:Previous reports have revealed that several cytokines (including platelet-derived growth factor-BB, transforming growth factors-β1 and insulin-like growth factor-1) can enhance the rate of bone formation and synthesis of extracellular matrix in orthopaedics or periodontology. This study aimed to determine the concentration of cytokines within platelet-rich fibrin microstructures and investigate whether there are differences in the different portions of platelet-rich fibrin, which has implications for proper clinical use of platelet-rich fibrin gel.METHODS:Whole blood was obtained from six New Zealand rabbits (male, 7 to 39 weeks old, weight 2.7-4 kg); it was then centrifuged for preparation of platelet-rich fibrin gels and harvest of plasma. The resultant platelet-rich fibrin gels were used for cytokine determination, histological analyses and scanning electron microscopy. All plasmas obtained were subject to the same cytokine determination assays for the purpose of comparison.RESULTS:Cytokines platelet-derived growth factor-BB and transforming growth factor-β1 formed concentration gradients from high at the red blood cell end of the platelet-rich fibrin gel (p=1.88×10-5) to low at the plasma end (p=0.19). Insulin-like growth factor-1 concentrations were similar at the red blood cell and plasma ends. The porosities of the platelet-rich fibrin samples taken in sequence from the red blood cell end to the plasma end were 6.5% ± 4.9%, 24.8% ± 7.5%, 30.3% ± 8.5%, 41.4% ± 12.3%, and 40.3% ± 11.7%, respectively, showing a gradual decrease in the compactness of the platelet-rich fibrin network.CONCLUSION:Cytokine concentrations are positively associated with platelet-rich fibrin microstructure and portion in a rabbit model. As platelet-rich fibrin is the main entity currently used in regenerative medicine, assessing cytokine concentration and the most valuable portion of PRF gels is essential and recommended to all physicians.
In this study, we demonstrated a natural silk fibroin protein (SFP) that was blended with a Chinese herbal extract (baicalein, BAI) to obtain an effective combination for producing electrospun nonwoven mats with anti-inflammatory and antibacterial functions. A series of SFP-based electrospun nonwoven mats with additives of varying compositions were produced and investigated. Performance comparisons showed that the SFP/polyvinylpyrrolidone (PVP)/BAI nonwoven mat is the optimal one. In vitro, SFP/PVP/BAI nonwoven mat is effective in inhibiting the formation of nitrite in lipopolysaccharide (LPS)-induced nitrite formation in Raw 264.7 macrophages model and the growth of Staphylococcus aureus (S. aureus). Especially in the case of SFP/PVP/BAI nonwoven mat, Bai has been proved to reach their maximum amount of releases of approximately 64.8% within 24 h of contact with water-based environment as compared to the SFP/BAI nonwoven mat (only 30.1% of release within 24 h). For in vivo experiments, a 1.2 cm × 1.2 cm wound area was created on the back of mice and seeded with 1 × 10 CFU/mL of S. aureus to induce an infected wound model. The experimental results show significant acceleration of the wound closure process in mice treated with SFP/PVP/BAI nonwoven mat (4 days of reduction as compared to the untreated group), reduction in infiltration of neutrophils, nitrite formation, and inhibition of growth of wound bacteria. Histological images of the group treated with SFP/PVP/BAI nonwoven mat showed a compete repair of skin hierarchy, increasing production of collagen fibers, and enhancement of angiogenesis. This may bring a better recovery of skin appearance after treatment. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 420-430, 2017.
We aimed to determine relationships between age and sex with cytokine content and distribution in human platelet-rich fibrin (PRF) gel. Rabbit PRF was harvested from whole blood (n = 6). Human PRF was collected from 36 healthy volunteers (1:1 men:women) without systemic diseases and not current undergoing medical treatment. Histological analysis and optical microscopy were used to assess the three-dimensional structure of the PRF network. Enzyme-linked immunosorbent assays, quantification of adenosine triphosphate, and bioluminescence imaging of PRF sections were used to assess cytokine and entrapped platelet distribution. Three-dimensional structures of fibrin networks revealed concentration gradients of the platelet-derived growth factor beta beta homodimer and the transforming growth factor-beta 1. Histological analysis of PRF sections (from the red blood cell end to the plasma end of a clot) showed a gradual increase in average porosity, most prominently in PRF clots from young and middle-aged men and women, and a decrease in compactness along the longitudinal axis of the PRF gel. The end of the PRF gel closest to the red blood cell layer is the essence of the PRF clot, and the ability to generate platelets depends on sex and age in humans.
This study proposes a feasible methodology to convert heterotopic auricular chondrocytes for articular cartilage repair, which may serve as potential alternative sources for cartilage repair.
Tendons are hypocellular and hypovascular tissues, and thus, their natural healing capacity is low. In this study, we sought to evaluate the efficacy of platelet-rich fibrin (PRF) to serve as a bioactive scaffold in promoting the healing of rabbit Achilles tendon injury. For in vitro study, the essence portion of PRF was determined through bioluminescent assay. Furthermore, we analyzed the time-sequential cytokines-release kinetics of PRF and evaluated their effects on tenocytes proliferation and tenogenic gene expressions. In animal study, the rabbit Achilles tendon defect was left untreated or implanted with normal/heat-denatured PRF scaffolds. Six weeks postoperatively, the specimens were evaluated through sonographic imaging and histological analysis. The results revealed significantly more activated platelets on bottom half of the PRF scaffold. Cytokine concentrations released from PRF could be detected from the first hour to six days. For the in vitro study, PRF enhanced cell viability and collagen I, collagen III, tenomodulin, and tenascin gene expression compared to the standard culture medium. For in vivo study, sonographic images revealed significantly better tendon healing in the PRF group in terms of tissue echogenicity and homogeneity. The histological analysis showed that the healing tissues in the PRF group had more organized collagen fiber, less vascularity, and minimal cartilage formation. In conclusion, bioactive PRF promotes in vitro tenocytes viability and tenogenic phenotypic differentiation. Administration of a PRF scaffold at the tendon defect promotes tissue healing as evidenced by imaging and histological outcomes.
CdSe nanocrystals (NCs) with different morphologies have been synthesized and applied as the acceptor in the active layer of the organic photovoltaic (OPV) devices. CdSe tetrapod (TP)/nanorod (NR) with zinc-blended seeds and wurtzite arms is prepared by seed growth method and mixed with poly(3-hexylthiophene) (P3HT): [6,6]-phenyl-C61-butyric acid methyl ester (PCBM). When the concentrations of CdSe in P3HT: PCBM system are 50 wt% optimally, the efficiency can be promoted about 4.3%, suggesting that an enhancement of 13.2% can be obtained and the addition of anisotropic CdSe NCs content in the active layer can be beneficial for the transport of electrons and light absorption in the OPV devices.
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