Elevation of N-acetyltransferase 10 in hippocampal neurons mediates depression- and anxiety-like behaviors.

Major depressive disorder (MDD) is one of the most debilitating and severe mental diseases globally. Increasing evidence has shown that epigenetics is critical for understanding brain function and brain disorders, including MDD. N-acetyltransferase 10 (NAT10), acting on histones, mRNA and other substrates, has been reported to be involved in epigenetic events, including histone acetylation and mRNA modifications. NAT10 is highly expressed in the brain. However, the potential effects of NAT10 on MDD are still unknown. Here, we exploited chronic mild stress (CMS) to induce anxiety- and depression-like behaviors in mice and found that the expression of NAT10 in the mouse hippocampus was upregulated after CMS treatment. Inhibition of NAT10 by pharmacological methods produced anxiolytic- and antidepressant-like effects. Neuron-specific overexpression of NAT10 in the hippocampus resulted in anxiety- and depression-like behaviors, accompanied by higher SIRT1 protein levels, and lower dendritic spine densities. Overall, it was found that elevation of NAT10 in hippocampal neurons is involved in the occurrence of anxiety- and depression-like behaviors, suggesting that NAT10 could be a potential new target for developing anxiolytics and antidepressants.

[Rhizoma Panacis majori reduces toxicity of chemotherapy in S180-bearing mice].

OBJECTIVE: To observe the attenuating effect of Rhizoma Panacis majoris (RPM) on toxicity of 5-fluorouracil (5-FU) chemotherapy in S180-bearing mice. METHODS: S180 cells were subcutaneously injected to the right armpit of the mice to establish the S180-bearing model, and thirty mice were randomly divided into untreated group, 5-FU group and 5-FU combined with RPM group (5-FU plus RPM group). The general condition of S180-bearing mice was observed. The white blood cells, red blood cells, and reticulocytes in the peripheral blood were counted, and the ratio of reticulocytes was measured too. The life-span of the S180-bearing mice was recorded. RESULTS: The white blood cell count and the ratio of reticulocytes in 5-FU plus RPM group were higher than those in 5-FU group (P<0.01). The average lifespan of 5-FU plus RPM group was 32.5 days and that of the 5-FU group was 23.5 days; there was a significant difference in the lifespan between the two groups (P<0.01). CONCLUSION: RPM can reduce the toxic effect of 5-FU and prolong the lifespan of S180-bearing mice.

Screening of QHF formula for effective ingredients from Chinese herbs and its anti-hepatic cell cancer effect in combination with chemotherapy.

BACKGROUND: Recent studies have shown that effective ingredients of Chinese herbs are used more and more widely in the treatment or co-treatment of cancers, however, they are usually used separately and there has been limited research about joint application of Chinese herbs in multi-modal treatment. The aim of this study was to screen a QHF (Q: Qingrejiedu, H: Huoxuehuayu and F: Fuzhengguben) formula for effective ingredients from Chinese medicines and assess its anti-hepatic cell cancer (HCC) effect in combination with chemotherapy. METHODS: Six effective ingredients from Chinese medicine were selected based on the previous literature and used in the study. The QHF formula and the best ratio of ingredients were evaluated in H(22) mouse (KM) models with solid tumors and ascites tumors by uniform design and monitoring inhibition of tumor growth and survival. We then observed the anti-hepatic cell cancer (HCC) effect of QHF when combined with cisplatin (DDP) in H(22) mouse (Balb/c) models with solid tumors and ascites tumors. Evaluating of the therapeutic effect included the general condition of the mice, inhibition of tumor growth, survival, changes in body weight, thymus index, spleen index and WBC counts. RESULTS: The optimal QHF dose ratio for anti-hepatic cell cancer treatment was: 800 mg/kg Cinobufotalin, 14 mg/kg Ginsenosides Rg3, 5.5 mg/kg PNS and 100 mg/kg Lentinan. Treatment was more efficient in inhibiting the growth of transplanted tumors in H(22) mice when using the QHF formula (55.91%) than using Cinobufotalin (33.25%), Ginsenosides Rg3 (35.11%), PNS (27.12%) or Lentinan (4.97%) separately. QHF also prolonged the life of H(22) ascites hepatic cancer mice more efficiently (38.13%) than Cinobufotalin (25.00%), Ginsenosides Rg3 (27.27%), PNS (23.30%) or Lentinan (24.43%). QHF combined with DDP could reduce DDP-induced leucopenia, spleen and thymus atrophy and other toxic reactions. Combining QHF with DDP the tumor growth inhibition reached 82.54% with a 66.83% increase in survival. CONCLUSIONS: QHF is more efficient in anti-hepatic cell cancer treatment than the single drugs that constitute the formula. QHF combined with DDP can attenuate tumor growth and suppresses the DDP-induced toxic reactions.