Ligustilide, a major bioactive component of Angelica sinensis, promotes bone formation via the GPR30/EGFR pathway.

Angelica sinensis (Oliv.) Diels is a widely-used traditional Chinese herbal medicine in treating osteoporosis. Ligustilide (LIG) is the main component of A. sinensis and is considered to be the most effective biologically active ingredient in this plant. LIG has been found to have multiple pharmacological activities, such as anti-atherosclerosis, neuroprotection, anticancer, anti-inflammatory and analgesic. However, little is known regarding its anti-osteoporotic effects. The aims of this study were to investigate any protective effect of LIG on bone formation. The results showed that LIG significantly ameliorated inhibition of bone formation in zebrafish caused by prednisolone. LIG promoted osteoblast differentiation, including that of the pre-osteoblastic cell line MC3T3-E1 and bone marrow mesenchymal stem cells. LIG greatly improved the viability of MC3T3-E1 cells exposed to H2O2, attenuated H2O2-induced apoptosis and increased the expression of Bcl-2. Furthermore, LIG treatment lead to marked activation of phosphorylated EGFR and ERK1/2. These effects could be obviously inhibited by blocking GPR30 signaling with the specific inhibitor G15. Collectively, the results reveal that GPR30 is a positive switch for LIG to increase bone formation via regulation of EGFR, and these results provide evidence for the potential of LIG to treat osteoporosis.

[Comparison of efficacy between sorafenib and sunitinib as first-line therapy for metastatic renal cell carcinoma and analyze prognostic factors for survival].

Objective: To investigate the efficacy and drug related adverse reactions of sorafenib and sunitinib as first-line tyrosine-kinase inhibitors (TKIs) for patients with metastatic renal cell carcinoma (mRCC) and analyze the clinical prognostic factor for survival. Methods: The data of 271 patients with metastatic renal cell carcinoma who had complete clinicopathological data were retrospectively analyzed, including 174 cases in sorafenib group and 97 cases in sunitinib group, to access patients' overall survival (OS) and progression-free survival (PFS). Prognostic values of all characteristics were determined by using univariate and multivariate Cox regression models. Results: The objective response rates (ORR) of the sorafenib and sunitinib groups were 14.9% and 19.6%, respectively, and the disease control rates (DCR) were 85.1% and 88.6%, respectively. No significant difference was found between the sorafenib and sunitinib group in ORR (P=0.325) or DCR (P=0.408). The most common grade 3 to 4 adverse events in the sorafenib group were hand-foot syndrome (6.7%), diarrhea (2.3%), and rash (2.3%). The most common grade 3 to 4 adverse events in the sunitinib group were neutropenia (6.2%), hand-foot syndrome (6.2%), and thrombocytopenia (4.6%). During the follow-up, 97 cases death occurred and 81 cases disease progression occurred in sorafenib group. The median PFS was 12 months (95% CI: 9-15 months), and the median OS was 25 months (95% CI: 21-29 months) in sorafenib group. While 74 cases death occurred and 40 cases disease progression occurred in sunitinib group, the median PFS was 12 months (95% CI: 10-12 months) and the median OS was 23 months (95% CI: 20-32 months) in sunitinib group. No significant difference was found between the sorafenib and the sunitinib group in PFS (P=0.771) or OS (P=0.548). Multivariate analysis showed Fuhrman grades (HR=1.358, 95%CI: 1.004-1.835), number of metastatic sites (HR=1.550, 95%CI: 1.143-2.101) and MSKCC risk grade (Intermediate risk group: HR=1.621, 95%CI: 1.117-2.232; Poor risk group: HR=2.890, 95%CI: 1.942-4.298) were independent prognostic factors for PFS. Fuhrman grades (HR=2.135, 95%CI: 1.533-2.974), number of metastatic sites (HR=1.774, 95%CI: 1.279-2.461) and MSKCC risk grade (Intermediate risk group: HR=1.415, 95%CI: 1.002-1.998; Poor risk group: HR=3.161, 95%CI: 2.065-4.838) were independent prognostic factors for OS. Conclusions: The results of this study indicate that sorafenib and sunitinib are both effective as the first-line TKIs for mRCC patients and sorafenib has comparable efficacy to sunitinib. But they have differences in the incidence of adverse effects. Fuhrman grades, number of metastatic sites and MSKCC risk grade are independent prognostic factors for mRCC patients.

[Advances in the research of effects of exosomes derived from stem cells on wound repair].

Exosomes are nano-vesicles released by many kinds of cells. Exosomes play a significant role in cell-to-cell communication and substance transportation through direct effect of signaling molecules on the cell membrane surface, intracellular regulation of cellular content during membrane fusion, or regulation of release of various bioactive molecules. Several studies have reported that culture supernatant of stem cells has some related exosomes to take part in wound repair. The secretion of exosomes is depended on the source and the physiological and pathological condition of deriving cells. How to stimulate the stem cells to produce exosomes maximally and their clinical application are worthy to explore. In this review, we summarize the biological function and application of exosomes derived from stem cells in wound repair.

Tea polyphenols inactivate Cronobacter sakazakii isolated from powdered infant formula.

This study evaluated the antimicrobial activity of tea polyphenols (TP) against 4 Cronobacter sakazakii strains with different sequence types (ST) isolated from powdered infant formula (PIF). The results showed that in normal saline, 5mg/mL of TP (pH 3.44) could eliminate approximately 7.0 log cfu/mL of C. sakazakii within 1 h; in rehydrated PIF, after acidification with HCl (pH 3.55), TP showed a stronger antibacterial activity compared with the controls (malic acid, ascorbic acid, and citric acid). Further, some differences were obvious in tolerance to TP between C. sakazakii strains with different ST. The tolerance of C. sakazakii CE1 (ST4) to TP was found to be greater than that of the other 3 C. sakazakii strains (ST1, ST8, and ST64). The results of recovered test and transmission electron microscope analysis revealed that the action of TP against C. sakazakii was an irreversible bactericidal process caused by leakage of cytoplasm. Taken together, these results indicated that TP had an effective bactericidal effect against C. sakazakii, and provided a new idea for preventing and inactivating C. sakazakii in PIF.

Alternative medicine: an update on cupping therapy.

To know the research progress of cupping therapy all over the world, the authors analyze the research of cupping therapy in recent 5 years. It indicates that cupping therapy can be applied to extensive curable disease, but has poor clinical evidence. Some improvements in the mechanism research of cupping therapy have been made, but it needs further research. The adverse events of cupping therapy attract attention. The standardization of cupping therapy has emerged.

Traditional Chinese medicine prevents inflammation in CCl4-related liver injury in mice.

Alternative medicines are being increasingly used and investigated in the management of a variety of disorders. Hepatitis is a common indication for the use of alternative therapies but evidence for the efficacy of many compounds is lacking. We have utilized a well-defined model of liver injury to study the efficacy of three herbal products designed to assist in the management of liver disease. Mice were exposed to carbon tetrachloride (CCL4) given intragastrically after they had been pretreated for five days with either saline or one of four doses of silymarin extract or CH100 (a Chinese herbal medicine comprising of 19 herbs) or one of two doses of CH101 (a Chinese herbal preparation designed to reduce fibrosis). Animals were sacrificed 24 hours after receiving CCL4. Liver enzymes and hepatic histology formed the basis for evaluating efficacy of the treatments. Each of the alternative medicines reduced the alanine amino transferase (ALT) elevation demonstrated after CCL4 injection. The high dose CH100 regimen was most effective in protecting against injury and this was confirmed with hepatic histology. Other doses of CH100, CH101 and silymarin were not shown to provide protection against the histological damage. In conclusion, Silymarin, CH100 and CH101 are able to reduce ALT elevation in animals exposed to CCL4. High dose CH100 provides protection from hepatocyte necrosis in this model. The data add to our understanding of the capacity some herbal medicines have to modify the reaction of the liver to a variety of insults and suggest the value of studying these agents further in human liver diseases.

Anticonvulsant doses of carbamazepine increase hippocampal extracellular serotonin in genetically epilepsy-prone rats: dose response relationships.

The antiepileptic drug carbamazepine produces dose related anticonvulsant effects in genetically epilepsy-prone rats (GEPRs) and most other animal seizure models. Carbamazepine releases serotonin as part of the pharmacodynamic action by which it suppresses convulsions in GEPRs and it releases serotonin in non-epileptic Sprague-Dawley rats. The two strains which make up the GEPR seizure model (moderate seizure GEPR-3s and severe seizure GEPR-9s) experience anticonvulsant effects in response to different doses of carbamazepine (GEPR-3 ED50 = 25 mg/kg; GEPR-9 ED50 = 3 mg/kg). The present study determined that carbamazepine produces a dose related increase in extracellular serotonin in each of the two GEPR strains. The doses of carbamazepine required to increase extracellular serotonin are similar to the doses required for an anticonvulsant effect in each of the strains. This result provides further support for the hypothesis that release of serotonin by carbamazepine is an important part of the pharmacodynamic action by which this drug suppresses seizures.

[Effect of intrathecal or intracerebroventricular administrition of OFQ on pain threshold and acpuncture analgesia in rats].

Orphanin FQ (OFQ) is a newly discovered 17-amino-acid peptide capable of inducing hyperalgesia. In the present study, the effects of OFQ on basal pain threshold and acupuncture anlgesia (AA) in rats were observed using the tail-flick test. It was found that intrathecal (i.t.) or intracerebroventricular (i.c.v.) administrition of 0.1 microgram OFQ had no effect on basal pain threshold of rats, while 1 microgram OFQ could lower the threshold. However, OFQ at both the doses (0.1 or 1.0 microgram) administered by either i.t. or i.c.v. injection could antagonize AA with that occuring in the brain being more prominent then in the spinal cord. When the rats were repeatedly treated with antisense oligonucleotide to block synthesis of OFQ receptor, pain threshold increased significantly. At such instance, when the OFQ was combined with acupuncture, the effect of AA showed no obvious change. The above results show that the OFQ at small dose has no effect on pain threshold but can lower it at larger dose; while in both cases OFQ can antagonize AA.

Antagonistic action of orphanin FQ on acupuncture analgesia in rat brain.

The influence of orphanin FQ (OFQ) (a newly discovered 17-amino acid peptide) on acupuncture analgesia (AA) was assessed in rat tail-flick model. Intracerebroventricular (i.c.v.) injection of OFQ (1 microgram) elicited a significant decrement of pain threshold which was abolished by the repeated pretreatment with antisense oligonucleotide (ASO) to OFQ receptor. Electroacupuncture (EA) induced an obvious analgesic effect; when OFQ was used combined with EA, it showed a dose-dependent effect on antagonizing the EA analgesia. When rat was repeatedly i.c.v. injected with ASO to block the synthesis of OFQ receptor, the EA analgesia was enhanced markedly. In this instance, the OFQ did not show antagonistic effect on EA analgesia any more. The results suggest that the OFQ play its antagonistic role on EA analgesia via activating OFQ receptor.