7-geranyloxycoumarin enhanced radiotherapy effects on human gastric adenocarcinoma cells.

Background: Gastric adenocarcinoma (GA) is a serious malignancy with growing incidence and mortality rate worldwide. The objective of the present study was to determine whether 7-geranyloxycoumarin, a natural monoterpene coumarin, could induce anticancer effects, in single use and/or in combination with anticancer drugs and ionizing radiation, on GA cells. Materials and Methods: 7-geranyloxycoumarin was synthesized by a reaction between 7-hydroxycoumarin and transgeranyl bromide. MKN45 cells were treated with 7-geranyloxycoumarin, and the viability of cells was determined by resazurin. Apoptosis was then evaluated by flow cytometric analysis using annexin V and propidium iodide, and the expression of P53 and BCL2 was analyzed by quantitative polymerase chain reaction (qPCR). Combinatorial effects of 7-geranyloxycoumarin with 5-fluorouracil (5-FU), cisplatin (CDDP), and X radiation were also evaluated. Results: Assessment of cell viability indicated that 7-geranyloxycoumarin induced its toxic effects in a time- and dose-dependent manner. This was confirmed by the detection of apoptotic cells, and qPCR results revealed a significant downregulation in BCL2 expression. Although combinatorial use of 7-geranyloxycoumarin + 5-FU or + CDDP did not improve cytotoxicity of anticancer drugs, significant increase in the effectiveness of applied radiations was detected upon pretreatment with 7-geranyloxycoumarin. Conclusion: Our findings provide valuable insights into single and combinatorial effects of 7-geranyloxycoumarin on the GA cells.

Biochemical Aspects of Scaffolds for Cartilage Tissue Engineering; from Basic Science to Regenerative Medicine.

Chondral defects are frequent and important causes of pain and disability. Cartilage has limited self-repair and regeneration capacity. The ideal approach for articular cartilage defects is the regeneration of hyaline cartilage with sustainable symptom-free constructs. Tissue engineering provides new strategies for the regeneration of functional cartilage tissue through optimized scaffolds with architectural, mechanical, and biochemical properties similar to the native cartilage tissue. In this review, the basic science of cartilage structure, interactions between proteins, stem cells, as well as biomaterials, scaffold characteristics and fabrication methods, as well as current and potential therapies in regenerative medicine will be discussed mostly from a biochemical point of view. Furthermore, the recent trends in scaffold-based therapies and supplementary factors in cartilage tissue engineering will be considered.

Evaluation of wound healing efficiency of vancomycin-loaded electrospun chitosan/poly ethylene oxide nanofibers in full thickness wound model of rat.

Electrospun hybrid nanofibers have been extensively regarded as drug carriers. This study tries to introduce a nano fibrous wound dressing as a new strategy for a topical drug-delivery system. The vancomycin (VCM)-loaded hybrid chitosan/poly ethylene oxide (CH/PEO) nanofibers were fabricated by the blend-electrospinning process. Morphological, mechanical, chemical, and biological properties of nanofibers were examined by SEM, FTIR, release profile study, tensile assay, Alamar Blue cytotoxicity evaluation, and antibacterial activity assay. In vivo wound healing activity of hybrid CH/PEO/VCM nanofibers was evaluated in full-thickness skin wounds of rats. The hybrid CH/PEO/VCM nanofibers were successfully fabricated in a nanometer. The CH/PEO/VCM 2.5% had higher Young's Modulus, better tensile strength, smaller fiber diameter with sustained-release profiles compared to CH/PEO/VCM 5%. All nanofibers did not show any significant cytotoxicity (P < 0.05) on the normal fibroblast cells. Also, VCM-load hybrid CH/PEO nanofibers successfully inhibited bacterial growth. The wound area in the rats treated with CH/PEO/VCM 2.5% was less than CH/PEO/VCM 5% treated group. According to histological evaluation, the CH/PEO/VCM 2.5% group showed the fastest wound healing than other treatment groups. Results of this study proposed that CH/PEO/VCM nanofibers could promote the wound healing process by reducing the side effects of VCM as a topical antimicrobial agent.

Topical green tea formulation with anti-hemorrhagic and antibacterial effects.

OBJECTIVES: Potentially preventable death from uncontrolled hemorrhage clearly indicates the importance of simple, fast and efficient ways to achieving hemostasis. The aim of this study was to develop a topical formulation of green tea extract for reducing bleeding that can be helpful in hemorrhage control. MATERIALS AND METHODS: Hydroalcoholic extract of green tea was isolated from Camellia sinensis and formulated in polyvinyl alcohol (PVA) to achieve two concentrations of 2% and 4% v/v. Folin-Ciocalteau assay was used to determine the total amount of tannins in extract. Rheological behavior of solutions was investigated by measuring viscosity at shear rates of 0-200 sec-1. Quantitative and qualitative microbial limit tests and minimum inhibitory concentration (MIC) assay were done. The effect of formulations on bleeding time was evaluated in an animal model. RESULTS: The total amount of tannin in green tea extract was 3.8% w/w and addition of green tea significantly increased the viscosity of PVA. The results of MIC assay showed that PVA could not inhibit the growth of bacteria, while, 716 µg/ml of green tea and 2860 µg/ml of green tea/PVA 4% inhibited the growth of Staphylococcus aureus and Pseudomonas aeruginosa. In an animal study both 2% and 4% formulations were able to stop hemorrhage approximately at an equal time compared with tranexamic acid (TXA) 50 mg/ml as a control and the lowest bleeding time was 6.4±0.51 sec for green tea/PVA 4%. CONCLUSION: Based on our results, the topical formulation of green tea extract in PVA has a great potential for anti-hemorrhage applications.

Teicoplanin-loaded chitosan-PEO nanofibers for local antibiotic delivery and wound healing.

Antibiotic-loaded nano-delivery systems offer an advanced approach to overcome several limitations associated with antibiotic therapy. Antibiotic-loaded nanofibers can be applied topically for skin and wound healing, post operation implants for the prevention of abdominal adhesion, and prophylaxis and treatment of infections in orthopedic surgery. Here, the authors report the development of local antibiotic delivery system using chitosan- polyethylene oxide (PEO) nanofibers for delivery of teicoplanin. Successful electrospinning of chitosan-PEO solution containing 2 and 4 w/v% teicoplanin resulted in uniform and bead-less nanofibers. Nanofibers were able to release teicoplanin up to 12 days. Antibacterial test in agar diffusion and time-kill study on Staphylococcus aureus also demonstrate that loading teicoplanin in chitosan-PEO nanofibers not only kept the antibacterial activity of antibiotic but also, enhanced it up to 1.5 to 2 fold. Teicoplanin loaded nanofibers did not show any cytotoxicity to human fibroblast. Moreover, in vivo study on rat full thickness wound model confirmed safety and efficacy of applying teicoplanin loaded nanofibers and significant improve in wound closure was observed especially with nanofibers containing 4% teicoplanin. The sustained release profile, enhanced drug activity, cytocompatibility, and significant wound healing activity affirm the potential applications of teicoplanin-loaded nanofibers in wound healing and local antibiotic delivery.

Impact of different intensities of forced exercise on deficits of spatial and aversive memory, anxiety-like behavior, and hippocampal BDNF during morphine abstinence period in male rats.

Forced exercise can alleviate cognitive-behavioral deficits in an experimental model of addiction. However, the effects of different intensities of forced exercise in improving behavioral, cognitive and biochemical deficits during morphine abstinence period are not well investigated. Thus, the current work examined the effects of different loads of forced exercise on cognition functions, anxiety behavior and BDNF changes in the hippocampus, and prefrontal cortex (PFC), and also serum levels of BDNF and corticosterone during the abstinent period in male rats. Animals received morphine injections (10 mg/kg, twice a day) for 10 consecutive days. Then, the animals were exposed to a 4-week forced exercise training program under low, moderate or high intensities (30 min per session on 5 days a week), which accompanied by behavioral and biochemical tests. In Experiment 1, anxiety-like behaviors using elevated plus maze (EPM), and light/dark box (L/D box) were examined. In Experiment 2, cognitive functions using T-maze alteration and passive avoidance tasks were tested, which accompanied by BDNF measurements in the hippocampus and PFC. In Experiment 3, serum levels of BDNF and corticosterone following the termination of forced exercise regimen were measured. Morphine-abstinent animals exhibited anxiogenic -like behaviors in the EPM, but not L/D box. They also exhibited impaired T-maze alternation performance and passive avoidance memory, and a decline in hippocampal BDNF, but not PFC. Forced exercise at a moderate intensity alleviated anxiety, cognitive and BDNF defects in morphine-abstinent animals. The high load exercise enhanced serum levels of corticosterone in both saline and morphine groups. Thus, regular moderate forced exercise may be beneficial in preserving cognitive and mood functions in male addicts during the abstinent period and drug rehabilitation.

Curcumin nanofibers for the purpose of wound healing.

Poor wound healing is a highly prevalent clinical problem with, as yet, no entirely satisfactory solution. A new technique, termed electrospinning, may provide a solution to improve wound healing. Due to their large surface area to volume ratio and porosity, the nanofibers created by electrospinning are able to deliver sustained drug release and oxygen to the wound. Using different types of polymers with varying properties helps strengthening nanofiber and exudates absorption. The nanofibers appear to have an ideal structure applicable for wound healing and, in combination with curcumin, can blend the anti-inflammatory and antioxidant properties of curcumin into a highly effective wound dressing. The use of suitable curcumin solvents and the slow release of curcumin from the nanofiber help in overcoming the known limitations of curcumin, specifically its low stability and limited bioavailability. Here, we review the studies which have been done on synthesized nanofibers containing curcumin, produced by the electrospinning technique, for the purpose of wound healing.

Current Concepts in Scaffolding for Bone Tissue Engineering.

Bone disorders are of significant worry due to their increased prevalence in the median age. Scaffold-based bone tissue engineering holds great promise for the future of osseous defects therapies. Porous composite materials and functional coatings for metallic implants have been introduced in next generation of orthopedic medicine for tissue engineering. While osteoconductive materials such as hydroxyapatite and tricalcium phosphate ceramics as well as some biodegradable polymers are suggested, much interest has recently focused on the use of osteoinductive materials like demineralized bone matrix or bone derivatives. However, physiochemical modifications in terms of porosity, mechanical strength, cell adhesion, biocompatibility, cell proliferation, mineralization and osteogenic differentiation are required. This paper reviews studies on bone tissue engineering from the biomaterial point of view in scaffolding. Level of evidence: I.