Metabonomics Study on the Infertility Treated With Zishen Yutai Pills Combined With In Vitro Fertilization-embryo Transfer.

Zishen Yutai Pills (ZYP) is a safe and well quality-controlled TCM preparation with promising effects in many fields of reproduction, including prevention of miscarriage, increase of pregnancy rate during in vitro fertilization-embryo transfer (IVF-ET). The plasma of patients was collected from a clinical trial, namely, "Effect of Traditional Chinese Medicine vs placebo on live births among women undergoing in vitro fertilization, a multi-center randomized controlled trial." Plasma samples were analyzed with metabonomics method. UPLC-MS technology was used to establish the plasma metabolic fingerprint. Multivariate statistical analysis was applied for comparing the differences of plasma metabolites between ZYP group and placebo group, 44 potential metabolites were screen out and identified. Pathway analysis was conducted with database mining. Compared with placebo, chemicals were found to be significantly down-regulated on HCG trigger day and 14 days after embryo transplantation, including trihexosylceramide (d18:1/26:1), glucosylceramide(d18:1/26:0), TG(22:6/15:0/22:6), TG(22:4/20:4/18:4). Compared with placebo, some chemicals were found to be significantly up-regulated on HCG trigger day and 14 days after embryo transplantation, i.e., PIP3(16:0/16:1), PIP2(18:1/18:1), tauroursodeoxycholic acid, L-asparagine, L-glutamic acid, kynurenic acid, 11-deoxycorticosterone, melatonin glucuronide, hydroxytyrosol. These metabolites were highly enriched in pathways including sphingolipid metabolism, alanine, aspartic acid and glutamic acid metabolism, aminoacyl tRNA biosynthesis, taurine and hypotaurine metabolism. This study revealed metabolic differences between subjects administered with ZYP and placebo. Relating metabolites were identified and pathways were enriched, providing basis on the exploration on the underlying mechanisms of ZYP combined with IVF-ET in the treatment of infertility.

[Chronic hepatotoxicity evaluation of Chinese medicinal herb Zishen Yutai pill prepared from Polygoni Multiflori Radix preparata in dogs].

To study the chronic hepatotoxicity of Chinese medicine Zishen Yutai pill (ZYP) prepared from Polygonum multiflorum with the recommended dosage in normal Beagle dogs. Low, middle and high doses of ZYP (1.5, 3.0, 6.0 g·kg⁻¹; i.e. 3×, 6× and 12× equivalent doses) were given orally to dogs for 39 consecutive weeks. At the same time, the same volume of deionized water was used as the solvent control group, one time a day. The general condition of the animals was observed every day during the period of administration, and the blood was collected before and 13, 26, 39, 43 weeks after administration to detect the biomarkers related to the hepatotoxicity of the dog serum. 2/7, 3/7 and 2/7 animals were dissected after 13, 39, and 43 weeks of administration to observe the pathological changes of the animal organs, weigh the mass of main organs and conduct pathological examination of the liver. As compared to the solvent control group, 11 liver hepatotoxicity traditional biomarkers such as ALT, AST were found no ZYP-related changes at month 3, 6, 9 of the administration and month 1 in recovery period; There was no significant difference in liver viscera index and liver pathology. Therefore, no obvious hepatotoxicity was shown by ZYP administered up to 6.0 g·kg⁻¹ for 9 months in normal dogs at doses of 1.5, 3.0, and 6.0 g·kg⁻¹.

HTNV-induced upregulation of miR-146a in HUVECs promotes viral infection by modulating pro-inflammatory cytokine release.

Increasing research has shown a link between viruses and miRNAs, such as miRNA-146a, in regulating virus infection and replication. In the current study, the association between miR-146a and hantaan virus (HTNV) infection in human umbilical vein endothelial cells (HUVECs) was investigated, with a focus on examining the expression of pro-inflammatory cytokines. The results showed that HTNV infection promoted the production of miR-146a in HUVECs and activated nuclear factor-κB (NF-κB) signaling, along with the upregulation of pro-inflammatory cytokines, including interleukin 8 (IL-8), C-C Motif Chemokine Ligand 5 (CCL5, also RANTES), interferon-inducible protein-10 (IP-10) and interferon beta (IFN-ß). Moreover, miR-146a exhibited a negative regulatory effect on the NF-κB pathway. Accordingly, a miR-146a inhibitor increased the expression of IL-8, CCL5, IP-10 and IFN-ß, whereas a miR-146a mimic reduced the levels of these cytokines. Consequently, exogenous transduction of miR-146a significantly enhanced HTNV replication in HUVEC cells. We also discovered that viral proteins (NP/GP) contributed to miR-146a expression via enhancement the activity of miR-146a promoter. In conclusion, these results imply the negative regulation of miR-146a on the production of HTNV-induced pro-inflammatory cytokines contributes to virus replication, which suggest that miR-146a may be regarded as a novel therapeutic target for HTNV infection.