Diarylheptanoids (AO-0001, AO-0002, and AO-0003) isolated from Alpinia officinarum inhibit proinflammatory mediators and exhibit cytotoxic and antiviral activity. However, the precise mechanisms of action of these diarylheptanoids are unknown as are their effects on expression of specific genes. Here, we used a translatome analysis to investigate the mechanisms and modes of action of these three diarylheptanoids. Polysome-associated messenger RNAs (mRNAs) were prepared from diarylheptanoids-treated and control cells from a human B lymphoblastoid cell line; these mRNA samples were then used for microarray analysis. Microarray Data Analysis Tool version 3.2 was used to analyze the microarray data analysis; this software uses pathway information of the WikiPathways for gene ontology analysis. Each of the diarylheptanoids caused upregulation or downregulation of the same 37 and 286 genes, respectively. Among the 37 upregulated genes, 16 were related to mRNA processing based on the WikiPathways analysis. Our findings provided new insights into the mode of action of diarylheptanoids from A. officinarum.

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ARHGAP10 is a member of the RhoGAP superfamily, and involved in RhoA/ROCK signaling. Recently, our group has identified ARHGAP10 gene mutation in Japanese schizophrenia patients by genome-wide CNV analysis. We also found that a ROCK inhibitor Y-27632 restored the impairment of neurite elongation of TH-positive neurons that had been differentiated from the patient-derived iPS cells. In this research, to clarify a potential role of RhoA/ROCK signal as a new therapeutic target for schizophrenia, we examined the effect of fasudil, a ROCK inhibitor, on MK-801induced behavioral impairment and neurotransmitter release in nucleus accumbens (NAc) in C57BL/6j male mice. We performed locomotor activity test, novel object recognition test (NORT), social interaction test (SI), and prepulse inhibition test (PPI). Fasudil (10-20 mg/kg) was intraperitoneally administered 5 min before the behavioral tests. We also measured the extracellular dopamine and serotonin levels in the NAc using an in vivo microdialysis method. Fasudil (10 or 20 mg/kg) restored MK-801-induced hyperlocomotion and the impairment of performance in the NORT, SI and PPI tests. Fasudil (20 μM) suppressed the depolarization-evoked dopamine and serotonin releases in the NAc, while it increased the basal serotonin levels. These observations suggest that the RhoA/ROCK signal has potential as a therapeutic target for schizophrenia and fasudil has some antipsychotic-like effects in a preclinical animal model of schizophrenia.

ISO/IEC 17025 : 2017 requires laboratories to verify the performance of methods before introducing them. ISO 16140-3 : 2021 employs LOD50 (the level of detection for which 50％ of tests give a positive result) as an index for evaluating the performance of microbial qualitative methods. While fecal coliforms and qualitative methods are widely implemented in Japan, their LOD50 values have not been established, making performance evaluation of these methods impossible at the time of introduction. As a result, we looked into estimating the LOD50 values of fecal coliforms and qualitative methods to evaluate the index of method performance. The fecal coliforms method had an LOD50 value of 19-31 CFU/mL and the method had an LOD50 value of 29-49 CFU/mL by laboratory personnels using samples without food matrix. We estimated LOD50 of six food samples using each method in a single laboratory. The LOD50 values of all foods calculated using the fecal coliforms method were in the range of 14-27 CFU/g and those calculated using the method were in the range of 25-48 CFU/g, indicating that these methods did not have low levels of sensitivity detection compared with skill variation. LOD50 values for food samples with the highest or lowest LOD50 in each method were compared among five laboratories. Because the estimated LOD50 values of both the methods were within four times of each laboratory result, which is the acceptable limit specified in ISO 16140-3 : 2021, they were assumed to be suitable values. This study is expected to be utilized as a benchmark in the verification of method performance in each laboratory.

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