The homeostasis of insulin-like growth factor-1 (IGF-1) is essential for metabolism, development and survival. Insufficient IGF-1 is associated with poor recovery from wounds whereas excessive IGF-1 contributes to growth of tumours. We have shown that cyclic glycine-proline (cGP), a metabolite of IGF-1, can normalise IGF-1 function by showing its efficacy in improving the recovery from ischemic brain injury in rats and inhibiting the growth of lymphomic tumours in mice. Further investigation in cell culture suggested that cGP promoted the activity of IGF-1 when it was insufficient, but inhibited the activity of IGF-1 when it was excessive. Mathematical modelling revealed that the efficacy of cGP was a modulated IGF-1 effect via changing the binding of IGF-1 to its binding proteins, which dynamically regulates the balance between bioavailable and non-bioavailable IGF-1. Our data reveal a novel mechanism of auto-regulation of IGF-1, which has physiological and pathophysiological consequences and potential pharmacological utility.

The aim of this study was to evaluate (+)-catechin and (−)-epigallocatechin gallate (EGCG) cellular uptake and transport across human intestinal Caco-2 cell monolayer in both the absence and presence of niosomal carrier in variable conditions. The effect of free drugs and drug-loaded niosomes on the growth of Caco-2 cells was studied. The effects of time, temperature, and concentration on drug cellular uptake in the absence or presence of its niosomal delivery systems were investigated. The intestinal epithelial membrane transport of the drug-loaded niosomes was examined using the monolayer of the human Caco-2 cells. The kinetics of transport, and the effect of temperature, adenosine triphosphate inhibitor, permeability glycoprotein inhibitor, multidrug resistance-associated protein 2 inhibitor, and the absorption enhancer on transport mechanism were investigated. It was found that the uptake of catechin, EGCG, and their niosomes by Caco-2 cells was 1.22±0.16, 0.90±0.14, 3.25±0.37, and 1.92±0.22 μg/mg protein, respectively (n=3). The apparent permeability coefficient values of catechin, EGCG, and their niosomes were 1.68±0.16, 0.88±0.09, 2.39±0.31, and 1.42±0.24 cm/second (n=3) at 37°C, respectively. The transport was temperature- and energy-dependent. The inhibitors of permeability glycoprotein and multidrug resistance-associated protein 2 and the absorption enhancer significantly enhanced the uptake amount. Compared with the free drugs, niosomal formulation significantly enhanced drug absorption. Additionally, drug-loaded niosomes exhibited stronger stability and lower toxicity. These findings showed that the oral absorption of tea flavonoids could be improved by using the novel drug delivery systems.

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Objective To evaluate the midterm results of the cementless S‐ROM modular femoral stem used with subtrochanteric transverse shortening osteotomy for the treatment of high hip dislocation secondary to hip pyogenic arthritis. Methods We retrospectively reviewed the data of 49 patients (49 hips) with an average infection quiescent period of 37.4 years who underwent cementless total hip arthroplasty (THA) with simultaneous subtrochanteric transverse shortening osteotomy from July 2008 to June 2012. There were 23 men and 26 women with a mean age of 44.3 years at the time of surgery. The following clinical outcomes were evaluated: the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score, Harris hip score (HSS), modified Merle d'Aubigne‐Postel hip (MAP) score, low back pain visual analog scale score, 12‐item short‐form health survey questionnaire score, limp, and Trendelenburg sign. Radiographic outcomes and complications were also evaluated. Results The mean follow‐up period was 8.7 years (range, 5.5–10 years). No infection recurrence was observed after THA. The average HSS significantly improved from 45.0 to 84.8. The WOMAC score improved from 70.1 ± 3.5 (range, 65–76) to 43.1 ± 13.4 (range, 21–67). The modified MAP score improved from 5.9 ± 1.9 (range, 3–9) to 14.3 ± 2.4 (range, 11–18). The low back pain visual analog scale score, 12‐item short‐form health survey questionnaire score, limp, and Trendelenburg sign also improved significantly. The average limb length discrepancy decreased from 39.6 mm (range, 30–55 mm) to 7.2 mm (range, 0–22 mm). Two patients had temporary sciatic nerve paralysis but recovered within 6 months without any functional defects; one had an intraoperative fracture fixed by cerclage wires. One hip required revision surgery because of femoral stem aseptic loosening. Conclusions The cementless S‐ROM modular femoral stem used with subtrochanteric transverse shortening osteotomy is safe and effective for high hip dislocation secondary to pyogenic arthritis and provides satisfactory midterm results. Significant improvements in clinical function were observed, as were high rates of stable fixation of the cementless implant, restoration of more normal limb lengths, and a low incidence of complications.

Background: Cervical cancer is one of the leading severe malignancies throughout the world. Sophra flavescens alkaloid (SFA) gels, a compound Traditional Chinese Medicine, has been clinically used in China for many years. Its individual active ingredients are matrine and oxymatrine, which has been showed that they can restrain primary tumorigenesis, while the underlying molecular mechanisms of SFA gels in cervical cancer cells remain unclear.Methods: To detect the effect of SFA gels and its active ingredients, CCK-8 assay and colony assay were used on cervical cancer cells proliferation. Transwell assay was used to detect cancer cell migration. Apoptosis and cell cycle arrest were used to detect whether SFA gels effect the cervical cancer cells proliferation. Western blot was used to detect whether SFA gels regulate the cervical cancer cells via the suppression of AKT/mTOR signaling pathway.Results: SFA gels can restrain cervical cancer cell proliferation, inhibit metastasis, induce cell cycle arrest in G2/M phase, induce cellular apoptosis through stimulation of Bax and E-cadherin, and suppression of Bcl-2, cyclin A, MMP2. Further study shows that SFA gels may regulate the cervical cancer cells via the suppression of AKT/mTOR signaling pathway.Conclusions: SFA gels, like its active ingredients, can restrain cervical cancer cells proliferation, suppress cervical cancer cell migration, induce the apoptosis and cell cycle arrest in cervical cancer cells. SFA gels may be a potential anti-tumor therapeutic agent for treating cervical cancer.