The comparison of plasma arsenic concentration and urinary arsenic excretion during treatment with Realgar-Indigo naturalis formula and arsenic trioxide in children with acute promyelocytic leukemia.

Realgar-Indigo naturalis formula (RIF) is a traditional Chinese medicine containing As4S4 and effective in treating acute promyelocytic leukemia (APL). The dose of RIF remains to be determined in pediatric patients. Comparison of plasma arsenic concentrations and toxicity between RIF and arsenic trioxide (ATO) treatment in APL may help to establish an appropriate therapeutic dose of RIF for children. From October 2018 to March 2020, 19 pediatric patients with APL treated with SCCLG-APL protocol were included, 9 in RIF group at 135 mg/kg/day orally three times daily, and 10 in ATO group at 0.16 mg/kg/day intravenously over 12 h daily. Peak and trough plasma arsenic concentrations were assayed at D1, 2, 7 and 14 of induction treatment. Urine arsenic excretions were assessed with spot urine samples and the measurements were adjusted using creatinine. Toxicities were compared between two groups. The plasma arsenic concentration reached steady state at D7 either in the RIF or ATO group, and the mean peak and trough concentrations were similar between two groups (P > 0.05), which were 0.54 µmol/L and 0.48 µmol/L in RIF group, and 0.63 µmol/L and 0.51 µmol/L in ATO group, respectively. Urine arsenic excretion rate was positively correlated with the concentration of plasma arsenic. The rates of treatment-related adverse events were similar in two groups. In conclusion, the dose of RIF at 135 mg/kg/day may be an appropriate therapeutic dose in children with APL. Urine arsenic level can be used as an indicator to estimate plasma arsenic concentration. Trial registration www.clinicaltrials.gov NCT02200978.

Tong-Xie-Yao-Fang improves intestinal permeability in diarrhoea-predominant irritable bowel syndrome rats by inhibiting the NF-κB and notch signalling pathways.

BACKGROUND: Tong-Xie-Yao-Fang (TXYF) has been shown to be effective in diarrhoea-predominant irritable bowel syndrome (IBS-D) patients. However, the underlying mechanism remains to be clarified. The aim of this study was to investigate the efficacy and related mechanisms of TXYF in an IBS-D rat model. METHODS: The IBS-D rat model was established with 4% acetic acid and evaluated by haematoxylin-eosin (HE) staining. Then, IBS-D rats were divided into control, TXYF and rifaximin groups and treated intragastrically with normal saline, TXYF and rifaximin, respectively, for 14 days. The following indicators were measured before and after treatment: defecation frequency, faecal water content (FWC) and colorectal distension (CRD). Histopathological changes in the distal colon were observed after treatment. The expression of OCLN and ZO1 in the distal colon of IBS-D rats reflected the intestinal mucosal permeability, as measured by qRT-PCR, western blot, and enzyme-linked immunosorbent assays (ELISAs). The NF-κB and Notch signalling pathways and inflammation-related factors were investigated. RESULTS: After treatment with TXYF, the defecation frequency, FWC and CRD were significantly lower than those in the model group (P < 0.05). HE staining showed that colonic epithelial cells (CECs) in the IBS-D rats displayed significant oedema, impaired intestinal mucosal integrity and an increased influx of inflammatory cells. A significant reduction in granulocyte and CEC oedema was observed after the administration of TXYF and rifaximin compared to that of the model group and blank group (P < 0.05). TXYF significantly upregulated the expression of OCLN and ZO-1 and downregulated inflammation-related factors (IL-6, IL-1ß, and TNF-α and the chemokine KC) in IBS-D rats compared to those in the model group rats (P < 0.05). In terms of the NF-κB and Notch signalling pathways, the expression of NICD, p-ERK, Hes-1 and p-P65 decreased significantly in the TXYF and rifaximin groups, while the expression of ATOH1 increased significantly compared to that in the model group (P < 0.05). CONCLUSION: TXYF can effectively improve intestinal permeability and enhance intestinal mucosal barrier function, which may be related to inhibition of the inflammatory cascade and the NF-κB and Notch signalling pathways.

Inhibition of TNF-α/IFN-γ induced RANTES expression in HaCaT cell by naringin.

CONTEXT: Naringin is a bioflavonoid derivative and is predominantly found in Citrus paradisi Macf., Citrus sinensis (Linn.) Osbeck, Citrus unshiu Marc., Citrus reticulata Blanco cv. Nobilis, Citrus tachibana (Makino) Tanaka, Citrus junos Sieb. ex Tanaka (Rutaceae), and related citrus species. It has anti-inflammatory effects that have been well-documented, but the mechanism is poorly characterized. OBJECTIVE: The effect of naringin on production of RANTES (regulated upon activation normal T-cell expressed and secreted) in human HaCaT cells was investigated here for the first time. MATERIALS AND METHODS: The HaCaT cells were cultured in Dulbecco's modified Eagle's medium (DMEM) and the proliferation of cell was determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT). The cells were divided into three groups including control group, tumor necrosis factor alpha (TNF-α)/interferon gamma (IFN-γ)-stimulated group, and naringin pretreatment group (first incubated in the presence of naringin and then exposed to TNF-α/IFN-γ). The concentration of RANTES in the supernatants was determined by enzyme-linked immunosorbent assay (ELISA). The expression of RANTES mRNA was analyzed by reverse transcription-polymerase chain reaction (RT-PCR). The expression of nuclear factor kappa B (NF-κB) P65 protein was detected with immunocytochemical method and western blot method. RESULTS: Naringin hardly inhibits HaCaT cells growth at concentrations rising from 0.25 to 1 mmol/L. However, RANTES expression detected in supernatant stimulated with TNF-α/IFN-γ reduced 15 and 16%, respectively, when cultured with 0.25, 0.5 mmol/L naringin. Furthermore, 1 mmol/L naringin significantly decreased RANTES mRNA level. Finally, naringin decreased the expression of NF-κB P65 protein in nuclei. DISCUSSION AND CONCLUSION: Naringin can inhibit the increased production of RANTES, which is partially via NF-κB-dependent signal pathway.