Anti-Fatigue Effects of Lycium barbarum Polysaccharide and Effervescent Tablets by Regulating Oxidative Stress and Energy Metabolism in Rats.

The purpose of this study was to investigate the anti-fatigue effect of natural Lycium barbarum polysaccharide (LBP) during exercise, develop a functional anti-fatigue effervescent tablet by applying LBP to practical products, and help patients who have difficulty swallowing conventional tablets or capsules. LBP was extracted with water, and DEAE-52 cellulose was used for purification. The chemical structure and monosaccharide composition of LBP by Fourier transform infrared spectroscopy (FI-IR) and ion chromatography (IC). Lycium barbarum polysaccharide effervescent tablets (LBPT) were prepared by mixing LBP and an excipient. Animal experiments showed that LBP and LBPT significantly increased the exhaustive swimming time in rats. LBP and LBPT improved biochemical markers in rat serum, such as lactic acid and creatine kinase, enhanced the antioxidant capacity of rat muscle, and reversed the decrease in serum glucose, ATP and glycogen content caused by exercise. Transmission electron microscopy showed that LBP and LBPT increased the density of mitochondria in rat liver. In addition, molecular experiments showed that LBP and LBPT could improve oxidative stress caused by exercise by regulating the Nrf2/HO-1 signaling pathway and regulating energy metabolism via the AMPK/PGC-1α signaling pathway.

Systematic review and meta-analysis comparing zoledronic acid administered at 12-week and 4-week intervals in patients with bone metastasis.

Zoledronic acid is used to treat patients with bone metastasis, but the optimal dosing interval remains controversial. We therefore performed a systematic review and meta-analysis to compare the efficacy and safety of a 12-week interval of zoledronic acid with the standard 4-week interval. Three randomized controlled trials comprising 2650 patients were analyzed. Using a random-effects model, pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. No differences in the occurrence of skeletal-related events (SREs: RR = 0.98; 95% CI = 0.86-1.12; P = 0.80) or grade 3/4 adverse events (RR = 0.91; 95% CI = 0.69-1.20; P = 0.52) were observed between the 12-week and 4-week groups. The 12-week group tended to have lower incidences of osteonecrosis of the jaw [13 (0.98%) vs. 23 (1.73%)] and kidney dysfunction [21 (1.68%) vs. 31 (2.45%)] than the 4-week group, though the difference did not reach statistical significance (RR = 0.58, 95% CI: 0.30-1.12; P = 0.11); (RR = 0.67, 95% CI: 0.39-1.15, P = 0.15). These data show that zoledronic acid administered at 12-week intervals instead of 4-week intervals does not increase the risk of SREs, and may reduce the incidence of osteonecrosis of the jaw and kidney dysfunction. This suggests the 12-week interval with zoledronic acid may be an acceptable treatment option.

In vivo pharmacokinetics, immunogenicity and mechanism of PEGylated antitumor polypeptide.

HM-3, An RGD (Arg-Gly-Asp)-modified polypeptide derived from endostatin, is a potent angiogenesis inhibitor. Its robust inhibitory effects on endothelial cell migration and tumor growth have been demonstrated by activity assay both in vitro and in vivo. However, HM-3 has relatively short half-life in vivo. In order to prolong its half-life and retain its safety and efficacy, previous studies modified HM-3 with four types of PEG (site-specific N-terminal modification), and the results showed that mPEG-SC20k-HM-3 was the most ideal modification product via activity evaluation in vivo. In the present study, we determined the pharmacokinetic properties, immunogenicity and binding targets of mPEG-SC20k-HM-3. The results showed that mPEG-SC20k-HM-3 had good linear pharmacokinetic properties in SD rats. The half-life of mPEG-SC20k-HM-3 was 43.76-fold longer than that of unmodified HM-3 after intravenous injection in SD rats. The administration frequency of the modified product (mPEG-SC20k-HM-3) was reduced from twice a day to once every 2 days, while the safety and efficacy were retained. The immunogenicity of mPEG-SC20k-HM-3 was significantly lower than that of HM-3 in BALB/c mice. Histochemical and immunohistochemical results showed that mPEG-SC20k-HM-3 could significantly inhibit angiogenesis and tumor growth, induce continuous necrosis, and reduce vessel density within tumor tissues. Furthermore, mPEG-SC20k-HM-3 could bind multi-target αvß3 and α5ß1 of integrin, and the major binding target was integrin αvß3. All of these results indicated that PEGylated HM-3 had a good application prospect.