Saponins isolated from Radix polygalae extent lifespan by modulating complement C3 and gut microbiota.

With the increase in human lifespan, population aging is one of the major problems worldwide. Aging is an irreversible progressive process that affects humans via multiple factors including genetic, immunity, cellular oxidation and inflammation. Progressive neuroinflammation contributes to aging, cognitive malfunction, and neurodegenerative diseases. However, precise mechanisms or drugs targeting age-related neuroinflammation and cognitive impairment remain un-elucidated. Traditional herbal plants have been prescribed in many Asian countries for anti-aging and the modulation of aging-related symptoms. In general, herbal plants' efficacy is attributed to their safety and polypharmacological potency via the systemic manipulation of the body system. Radix polygalae (RP) is a herbal plant prescribed for anti-aging and the relief of age-related symptoms; however, its active components and biological functions remained un-elucidated. In this study, an active methanol fraction of RP containing 17 RP saponins (RPS), was identified. RPS attenuates the elevated C3 complement protein in aged mice to a level comparable to the young control mice. The active RPS also restates the aging gut microbiota by enhancing beneficial bacteria and suppressing harmful bacteria. In addition, RPS treatment improve spatial reference memory in aged mice, with the attenuation of multiple molecular markers related to neuroinflammation and aging. Finally, the RPS improves the behavior and extends the lifespan of C. elegans, confirming the herbal plant's anti-aging ability. In conclusion, through the mouse and C. elegas models, we have identified the beneficial RPS that can modulate the aging process, gut microbiota diversity and rectify several aging-related phenotypes.

CBX7 regulates stem cell-like properties of gastric cancer cells via p16 and AKT-NF-κB-miR-21 pathways.

BACKGROUND: Chromobox protein homolog 7 (CBX7), a member of the polycomb group (PcG) family of proteins, is involved in the regulation of cell proliferation and cancer progression. PcG family members, such as BMI, Mel-18, and EZH2, are integral constituents of the polycomb repressive complexes (PRCs) and have been known to regulate cancer stem cell (CSC) phenotype. However, the role of other PRCs' constituents such as CBX7 in the regulation of CSC phenotype remains largely elusive. This study was to investigate the role of CBX7 in regulating stem cell-like properties of gastric cancer and the underlying mechanisms. METHODS: Firstly, the role of CBX7 in regulating stem cell-like properties of gastric cancer was investigated using sphere formation, Western blot, and xenograft tumor assays. Next, RNA interference and ectopic CBX7 expression were employed to determine the impact of CBX7 on the expression of CSC marker proteins and CSC characteristics. The expression of CBX7, its downstream targets, and stem cell markers were analyzed in gastric stem cell spheres, common cancer cells, and gastric cancer tissues. Finally, the pathways by which CBX7 regulates stem cell-like properties of gastric cancer were explored. RESULTS: We found that CBX7, a constituent of the polycomb repressive complex 1 (PRC1), plays an important role in maintaining stem cell-like characteristics of gastric cancer cells via the activation of AKT pathway and the downregulation of p16. Spearman rank correlation analysis showed positive correlations among the expression of CBX7 and phospho-AKT (pAKT), stem cell markers OCT-4, and CD133 in gastric cancer tissues. In addition, CBX7 was found to upregulate microRNA-21 (miR-21) via the activation of AKT-NF-κB pathway, and miR-21 contributes to CBX7-mediated CSC characteristics. CONCLUSIONS: CBX7 positively regulates stem cell-like characteristics of gastric cancer cells by inhibiting p16 and activating AKT-NF-κB-miR-21 pathway.

The Effect of Low-Intensity Ultrasound on Brain-Derived Neurotropic Factor Expression in a Rat Sciatic Nerve Crushed Injury Model.

Low-intensity ultrasound (LIU) can improve nerve regeneration and functional recovery after peripheral nerve crush injury, but the underlying mechanism is not clear. The objective of this study was to examine the effects of LIU on rat sciatic crush injury and to investigate a possible molecular mechanism. Adult male Sprague-Dawley rats underwent left sciatic nerve crush surgery and were then randomized into two groups: a treatment group that received LIU every other d, and a control group that received sham exposure. Compared with rats in the control group, rats in the treatment group had higher sciatic nerve function indexes, compound muscle action potentials, wet weight ratios of the target muscle and mRNA expression of brain-derived neurotropic factor (BDNF) in the crushed nerve and ipsilateral dorsal root ganglia. Our findings suggest that LIU might promote injured nerve regeneration by stimulating BDNF release.

[Experimental study on Buyang Huanwu decoction ([Chinese characters: see text]) for promoting functional recovery of crushed common peroneal nerve in rats].

OBJECTIVE: To study the effects of Buyang Huanwu Decoction ([Chinese characters: see text]) on promoting functional recovery of crushed common peroneal nerve in rats. METHODS: Thirty Sprague-Dawley rats were subjected to produce common peroneal nerve injuries model,and the length of injury was 5 mm. All the rats were divided into 3 groups: BYHWD group, mecobalamin group and model group. The drugs were given by gavage daily for 18 days. Footprint test was performed at the 18th day after surgery to evaluate toe spread function (TSF). Electrophysiology was performed at the 18th day after operation to determine the nerve conduct velocity (NCV). The wet weight ratio and section area of tibial muscle were also measured. RESULTS: (TSF:At the 18th day after operation, the TSF in BYHWD group (-0.15 +/- 0.07) increased significantly compared with that of model group (-0.25 +/- 0.07) (P < 0.01); the TSF in mecobalamin group (-0.17 +/- 0.08) also increased notably compared with that of model group (P < 0.01).(2) NCV: the NCV in BYHWD group [(18.36 +/- 2.74) m/s] (P < 0.01l) and in mecobalamin group [(16.32 +/- 3.54) m/s] (P < 0.05) also increased significantly compared with that of model group [(9.08 +/- 2.56) m/s]; there was striking variation between model group and mecobalamin group (P < 0.05). (3) Wet weight ratio: the wet weight ratio in BYHWD group [(64.21 +/- 2.92)%] (P < 0.01)and in mecobalamin group [(62.43 +/- 3.21)%] (P < 0.01) all increased significantly compared with that of model group [(54.27 +/- 2.05)%]. (4) The section area of tibial muscle: the section area of tibial muscle in BYHWD group [(654.21 +/- 42.92) cm2] (P < 0.01) and in mecobalamin group [(638.43 +/- 93.21) cm2] (P < 0.01) all increased significantly compared with that of model group [(574.27 +/- 52.05) cm2]; there was also striking variation between model group and mecobalamin group (P < 0.05). CONCLUSION: BYHWD can promotes functional recovery of crushed nerve as a result of accelerating recovery of TSF, raising NCV and delaying the decrease of tibial muscle section area and wet weight ratio.

[Proteomic analysis of rat astrocytes and C6 glioma cells].

OBJECTIVE: To compare the protein profiles between glioma cells and normal astrocytes. METHODS: Proteomic assay was performed on human C6 glioma cells and purified SD rat astrocytes. Two-dimensional gel electrophoresis (2-DE) and PDQuest software were applied for the comparison of protein image between the C6 cells and astrocytes. The differential protein spots were identified with Matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) and further bioinformatic analysis. The differential expression of the interesting genes was confirmed by semi-quantitative RT-PCR. RESULTS: Twenty-four differential protein spots were revealed by 2-DE assay. The peptide mass fingerprints (PMFs) of 17 proteins were obtained by MALDI-TOF-MS. Among them, six proteins were determined by further bioinformatic analysis. Compared with the expression level in astrocytes, the identified proteins showed higher expression level in the C6 glioma cells including phosphoglycerate mutase 1, glutathione S-transferase P (GST P), annexin A2 and calreticulin, while the proteins showed lower expression level included vimentin and gamma-actin. The results of RT-PCR confirmed the differential expressions of phosphoglycerate mutase 1, annexin A2 and vimentin identified by 2-DE assay. CONCLUSION: The identified proteins differentially expressed in C6 cells and astrocytes are associated with many important cellular processes and functions such as anaerobic glycolysis, cytoskeleton organization, biotransformation, and signal transduction, and play important roles in tumor growth, migration, and anti-cancer drug resistance.