[External therapy of plasma cell mastitis by jiuyi powder using partial least-squares discriminant analysis: a safety analysis].

OBJECTIVE: To evaluate the safety and the clinical value of external use of jiuyi Powder (JP) in treating plasma cell mastitis using partial least-squares discriminant analysis (PLSDA). METHODS: Totally 50 patients with plasma cell mastitis treated by external use of JP were observed and biochemical examinations of blood and urine detected before application, at day 4 after application, at day 1 and 14 after discontinuation. Blood mercury and urinary mercury were detected before application, at day 1, 4, and 7 after application, at day 1 and 14 after discontinuation. Urinary mercury was also detected at 28 after discontinuation and 3 months after discontinuation. The information of wound, days of external application and the total dosage of external application were recorded before application, at day 1, 4, and 7 after application, as well as at day 1 after discontinuation. Then a discriminant model covering potential safety factors was set up by PLSDA after screening safety indices with important effects. The applicability of the model was assessed using area under ROC curve. Potential safety factors were assessed using variable importance in the projection (VIP). RESULTS: Urinary ß2-microglobulin (ß2-MG), urinary N-acetyl-ß-D-glucosaminidase (NAG), 24 h urinary protein, and urinary α1-microglobulin (α1-MG) were greatly affected by external use of JP in treating plasma cell mastitis. The accuracy rate of PLSDA discriminate model was 74. 00%. The sensitivity, specificity, and the area under ROC curve was 0. 7826, 0. 7037, and 0. 8084, respectively. Three factors with greater effect on the potential safety were screened as follows: pre-application volume of the sore cavity, days of external application, and the total dosage of external application. CONCLUSIONS: PLSDA method could be used in analyzing bioinformation of clinical Chinese medicine. Urinary ß2-MG and urinary NAG were two main safety monitoring indices. Days of external application and the total dosage of external application were main factors influencing blood mercury and urine mercury. A safety classification simulation model of treating plasma cell mastitis by external therapy of JP was established by the two factors, which could be used to assess the safety of external application of JP to some extent.

CPEB1, a novel risk gene in recent-onset schizophrenia, contributes to mitochondrial complex I defect caused by a defective provirus ERVWE1.

BACKGROUND: Schizophrenia afflicts 1% of the world population. Clinical studies suggest that schizophrenia patients may have an imbalance of mitochondrial energy metabolism via inhibition of mitochondrial complex I activity. Moreover, recent studies have shown that ERVWE1 is also a risk factor for schizophrenia. Nevertheless, there is no available literature concerning the relationship between complex I deficits and ERVWE1 in schizophrenia. Identifying risk factors and blood-based biomarkers for schizophrenia may provide new guidelines for early interventions and prevention programs. AIM: To address novel potential risk factors and the underlying mechanisms of mitochondrial complex I deficiency caused by ERVWE1 in schizophrenia. METHODS: Quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay were used to detect differentially expressed risk factors in blood samples. Clinical statistical analyses were performed by median analyses and Mann-Whitney U analyses. Spearman's rank correlation was applied to examine the correlation between different risk factors in blood samples. qPCR, western blot analysis, and luciferase assay were performed to confirm the relationship among ERVWE1, cytoplasmic polyadenylation element-binding protein 1 (CPEB1), NADH dehydrogenase ubiquinone flavoprotein 2 (NDUFV2), and NDUFV2 pseudogene (NDUFV2P1). The complex I enzyme activity microplate assay was carried out to evaluate the complex I activity induced by ERVWE1. RESULTS: Herein, we reported decreasing levels of CPEB1 and NDUFV2 in schizophrenia patients. Further studies showed that ERVWE1 was negatively correlated with CPEB1 and NDUFV2 in schizophrenia. Moreover, NDUFV2P1 was increased and demonstrated a significant positive correlation with ERVWE1 and a negative correlation with NDUFV2 in schizophrenia. In vitro experiments disclosed that ERVWE1 suppressed NDUFV2 expression and promoter activity by increasing NDUFV2P1 level. The luciferase assay revealed that ERVWE1 could enhance the promoter activity of NDUFV2P1. Additionally, ERVWE1 downregulated the expression of CPEB1 by suppressing the promoter activity, and the 400 base pair sequence at the 3' terminus of the promoter was the minimum sequence required. Advanced studies showed that CPEB1 participated in regulating the NDUFV2P1/NDUFV2 axis mediated by ERVWE1. Finally, we found that ERVWE1 inhibited complex I activity in SH-SY5Y cells via the CPEB1/NDUFV2P1/NDUFV2 signaling pathway. CONCLUSION: In conclusion, CPEB1 and NDUFV2 might be novel potential blood-based biomarkers and pathogenic factors in schizophrenia. Our findings also reveal a novel mechanism of ERVWE1 in the etiology of schizophrenia.

Hepatitis B core antigen modulates exosomal miR-135a to target vesicle-associated membrane protein 2 promoting chemoresistance in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. The association of hepatitis B virus (HBV) infection with HCC is hitherto documented. Exosomal miRNAs contribute to cancer progression and chemoresistance. HBV X protein has been known to modulate miRNAs that facilitate cell proliferation and the process of hepatocarcinogenesis. However, there has been no report on hepatitis B core antigen (HBc) regulating exosomal miRNAs to induce drug resistance of HCC cells. AIM: To elucidate the mechanism by which HBc promotes Doxorubicin hydrochloride (Dox) resistance in HCC. METHODS: Exosomes were isolated by ultracentrifugation. The morphology and size of exosomes were evaluated by Dynamic Light Scattering (DLS) and transmission electron microscopy (TEM). The miRNAs differentially expressed in HCC were identified using The Cancer Genome Atlas (TCGA) database. The level of miR-135a-5p in patient tissue samples was detected by quantitative polymerase chain reaction. TargetScan and luciferase assay were used to predict and prove the target gene of miR-135a-5p. Finally, we identified the effects of miR-135a-5p on anti-apoptosis and the proliferation of HCC in the presence or absence of Dox using flow cytometry, Cell counting kit 8 (CCK-8) assay and western blot. RESULTS: We found that HBc increased the expression of exosomal miR-135a-5p. Integrated analysis of bioinformatics and patient samples found that miR-135a-5p was increased in HCC tissues in comparison with paracancerous tissues. Bioinformatic analysis and in vitro validation identified vesicle-associated membrane protein 2 (VAMP2) as a novel target gene of miR-135a-5p. Functional assays showed that exosomal miR-135a-5p induced apoptosis protection, cell proliferation, and chemotherapy resistance in HCC. In addition, the rescue experiment demonstrated that VAMP2 reversed apoptosis protection, cell growth, and drug resistance by miR-135a-5p. Finally, HBc promoted HCC anti-apoptosis, proliferation, and drug resistance and prevented Dox-induced apoptosis via the miR-135a-5p/VAMP2 axis. CONCLUSION: These data suggested that HBc upregulated the expression of exosomal miR-135a-5p and promoted anti-apoptosis, cell proliferation, and chemical resistance through miR-135a-5p/VAMP2. Thus, our work indicated an essential role of the miR-135a-5p/VAMP2 regulatory axis in chemotherapy resistance of HCC and a potential molecular therapeutic target for HCC.