Comparison between liraglutide alone and liraglutide in combination with insulin on osteoporotic rats and their effect on bone mineral density.

OBJECTIVES: To compare the therapeutic efficacy of liraglutide (LRG) single drug combined with insulin (Ins) on osteoporosis in rats and its effect on bone mineral density (BMD). A rat model of diabetes combined with osteoporosis was established. METHODS: 40 Sprague-Dawley rats were divided into four groups (blank, control, LRG and LRG+Ins). Serum levels of CrossLaps, procollagen type I N propeptide (PINP), alkaline phosphatase (AKP) and osteocalcin (BGP) were detected by ELISA. Blood glucose was measured by its reaction with glucose oxidase. Serum insulin was analyzed by radioimmunology. Bone calcium and phosphorus contents were also recorded. ELISA was used to detect inflammatory factors. Bone mineral density (BMD) measurement was also performed. RESULTS: BMD of the control group was significantly lower than that of the other three groups (p<0.05) and BMD of the LRG + Ins group was significantly higher than that of the LRG group (p<0.05). The inflammatory factors of the control group were significantly higher than those in the other three groups (p<0.05). The inflammatory factors were negatively correlated with BMD (p<0.05). CONCLUSIONS: liraglutide in combination with insulin for the treatment of diabetes complicated with osteoporosis can reduce blood glucose in vivo, promote production of islet, effectively improve osteoporosis symptoms, increase BMD and reduce the levels of inflammatory factors in vivo.

Hollow carbon dots labeled with FITC or TRITC for use in fluorescent cellular imaging.

Hollow carbon dots (HCDs) were prepared by a solvothermal method and conjugated to either tetramethyl rhodamine isothiocyanate (TRITC) or fluorescein-5-isothiocyanate (FITC). This resulted in HCDs with bright red or green fluorescence, with excitation/emission peaks at 550/580 and 491/520 nm, respectively. The nanocomposites are well water-soluble, remarkably photostable and biocompatible. In addition, the fluorescence of the composites is more stable in a reactive oxygen environment than the free dyes. Confocal images indicate that the nanoparticles quickly enter A549 cells and mainly accumulate in the cytoplasm. The wavelength of functionalized HCDs can be regulating via coupling the HCDs to different dyes. These results demonstrate that these composite materials can be very promising reagents for biological labeling and imaging. Graphical abstract Schematic of the preparation of hollow carbon dots conjugated to tetramethyl rhodamine isothiocyanate (RHCDs) by solvothermal method. The material is water-soluble, remarkably photostable and biocompatible. It was applied to cellular labeling and imaging.

Enhancing the peroxidase-like activity of ficin by rational blocking thiol groups for colorimetric detection of biothiols.

The peroxidase-like activity of ficin is relatively low, which limits its application. It was found that thiol groups of ficin could inhibit its peroxidase-like activity. So, two procedures, i.e., direct blocking with N-ethylmaleimide (NEM), or using tris (2-carboxyethyl) phosphine hydrochloride (TCEP) to interrupt disulfide bonds then blocking thiol groups with NEM, were applied to block thiol groups of ficin, ficin-NEM (ficin-N) and ficin-TCEP-NEM (ficin-TN) were produced, respectively. The blocking of thiol groups accelerated the peroxidase activity dramatically. The peroxidase catalytic activity of ficin-N and ficin-TN toward the peroxidase substrate 3,3',5,5'-tetramethylbenzidine (TMB) oxidation by H2O2 was about 2.5-fold and 5-fold increase compared with ficin, respectively, which accompanied a color change from colorless to blue and followed classic Michaelis-Menten model. The kinetic parameters indicated that higher affinity of ficin-N (Km = 0.31) and ficin-TN (Km = 0.39) to H2O2 compared with ficin (Km = 0.58), and ficin-TN had the highest Kcat which increased by 6.5 times and 4.5 times for TMB and H2O2, respectively. According to these findings, a colorimetric method with high sensitivity for the detection of biothiols was developed due to sulfhydryl compounds inhibited the peroxidase activity of ficin. Comparing with ficin and ficin-N, ficin-TN had the widest detection range (0.01-16 µM) and the lowest detection limit (3 nM). The practical applications of ficin-TN for biothiol determination in human serum samples have been demonstrated with satisfactory results. Ficin-N and ficin-TN are promising to apply to the bioanalysis.

Tuning the fluorescence performance of carbon dots with a reduction pathway.

A reduction pathway was developed to tune the fluorescence quantum yield (QY) and emission wavelength of carbon dots (CDs). Reducing the original CDs (QY ca. 1.55%, maximum emission ca. 520 nm) with NaBH4 increased QY to 7.25% and blue-shifted the maximum emission to 450 nm. Treating the original CDs with LiAlH4 increased QY to ca. 7.44% and blue-shifted the maximum emission to 345 nm. The distinct fluorescence characteristics of the original CDs, NaBH4-treated CDs, and LiAlH4-treated CDs were conferred by their differing surface groups. Moreover, the original CDs, NaBH4-treated CDs, and LiAlH4-treated CDs responded differently to a specific oxidizer of hydroxyl groups. The increase in the fluorescence QY and blue-shift of the emission wavelength were explained. This study provides a foundation for the preparation and tuning of CDs with excellent fluorescence performance, as well as for the development CD-based fluorescent probes.

Efficacy of hyaluronic acid after knee arthroscopy: A systematic review and meta-analysis.

OBJECTIVE: To investigate the effect of hyaluronic acid on functional recovery and pain control in patients following knee arthroscopy. DESIGN: A systematic review and meta-analysis was conducted to explore the efficacy of hyaluronic acid following knee arthroscopy. SUBJECTS AND METHODS: Randomized controlled trials (RCTs) assessing the effect of hyaluronic acid in knee arthroscopy were included. A meta-analysis was performed using the random-effect model. RESULTS: Six RCTs involving 310 patients were included in the meta-analysis. Overall, compared with control intervention following knee arthroscopy, hyaluronic acid treatment was found to significantly increase Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores (mean difference 11.43; 95% confidence intervals (95% CI) 1.39-21.47; p = 0.03), but had no impact on pain scores at 2 weeks (mean difference -0.16; 95% CI -0.81-0.49; p = 0.63), pain scores at 6 weeks (mean difference 0.01; 95% CI -0.86-0.89; p = 0.98), pain scores at 12 weeks (mean difference -0.51; 95% CI -1.56-0.53; p = 0.34). In addition, pain on motion was significantly reduced after knee arthroscopy (risk ratio (RR) 0.22; 95% CI 0.06-0.79; p = 0.02). CONCLUSION: Compared with control intervention after knee arthroscopy, hyaluronic acid treatment was found to significantly improve WOMAC score and decrease pain on motion, but had no substantial influence on pain scores at 2, 6 and 12 weeks after knee arthroscopy.

Intrinsic Peroxidase-like Activity of Ficin.

Ficin is classified as a sulfhydryl protease isolated from the latex of fig trees. In most cases, a particular enzyme fits a few types of substrate and catalyzes one type of reaction. In this investigation, we found sufficient proofs for the intrinsic peroxidase-like activity of ficin and designed experiments to examine its effectiveness in a variety of scenarios. Ficin can transform peroxidase substrates to colored products in the existence of H2O2. Our results also indicate that the active sites of peroxidase-like activity of ficin are different from that of protease, which reveals that one enzyme may catalyze more than one kind of substrate to perform different types of reactions. On the basis of these findings, H2O2 releasing from MCF-7 cells was detected successfully. Our findings support a wider application of ficin in biochemistry and open up the possibility of utilizing ficin as enzymatic mimics in biotechnology and environmental monitoring.

Detection of glucose based on the peroxidase-like activity of reduced state carbon dots.

It was found that reduced state carbon dots (r-CDs) possessed intrinsic peroxidase-like activity, and could catalytically oxidize 3,3',5,5'-tetramethylbenzidine (TMB) by H2O2 to produce a color reaction. The effects of temperature, pH, incubating time and the concentration of H2O2 and TMB on catalytic activity of r-CDs were investigated. Finally we calculated the kinetic constant was ca. 0.00729min(-1) and applied r-CDs to glucose sensing by coupling glucose oxidase. As low as 2µM H2O2 could be detected with a linear range from 0.010 to 0.40mM via this method. This study offered a simple, sensitive, and high selectivity method for glucose determination even in serum.