Sonodynamic inactivation of gram-negative and gram-positive bacteria in the presence of phenothiazine compounds toluidine blue and azurin A.

BACKGROUND: Sonodynamic antimicrobial chemotherapy (SACT) is an effective antimicrobial treatment that can avoid the production of drug-resistant bacteria. Design and development of new high-efficiency sonosensitizers play a key role in the practical application of SACT. METHODS: The bacteriostatic effects of two phenothiazine compounds, toluidine blue (TB) and azure A (AA) combined with ultrasonic (US) on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were studied, and the sonodynamic antibacterial activities of TB and AA were compared. The reactive oxygen species (ROS) and the types of ROS produced in the sonodynamic system were detected and the sonodynamic mechanisms of TB and AA were proposed. RESULTS: The sonodynamic bacteriostasis mediated by TB and AA increased with the increasing concentration of sonosensitizer, the extension of sonication time and the increase of reaction temperature. The production of ROS was the main reason that TB and AA had excellent sonodynamic antibacterial performance. Singlet oxygen (1O2) and hydroxyl radical (•OH) were the main ROS types in the sonodynamic antibacterial system. The ROS produced by the combined action of AA and US was higher than that of TB. CONCLUSION: Both TB and AA displayed excellent sonodynamic antibacterial activities. Moreover, AA had a higher sonodynamic activity than TB. The electron donation effect and steric hindrance effect of the methyl group of phenothiazine parent nucleus of TB might be the cause of the decrease of its sonodynamic activity. These results would provide a valuable reference for the further study of phenothiazines sonosensitizers and their clinical application in SACT.

Subchronic toxic effects of bisphenol A on the gut-liver-hormone axis in rats via intestinal flora and metabolism.

Background: Bisphenol A (BPA), a characteristic endocrine disruptor, is a substance that seriously interferes with the human endocrine system and causes reproductive disorders and developmental abnormalities. However, its toxic effects on the gut-liver-hormone axis are still unclear. Method: Male and female rats were exposed to BPA (300 mg/kg) by oral gavage for 60 consecutive days. H&E staining was used for histopathological evaluation, and the serum biochemical indexes were determined using an automatic analyzer. The 16S rRNA gene sequencing was used to detect the intestinal microbial diversity, and the GC-MS was used to analyze the contents of short-chain fatty acids (SCFAs) in colon contents. UPLC-QTOF MS was used to analyze the related metabolites. The ELISA method was used to assess the levels of serum inflammatory factors. Results: Histopathological analysis indicated that the liver, heart, and testis were affected by BPA. There was a significant effect on alanine aminotransferase (ALT), triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL) in the male-BPA group (P < 0.05), and globulin (GLB), indirect bilirubin (IBIL), alkaline phosphatase (ALP), ALT, TG, TC, high-density lipoprotein (HDL), and creatinine (Cr) in the female-BPA group (P < 0.05). Metagenomics (16S rRNA gene sequencing) analysis indicated that BPA reduced the diversity and changed the composition of gut microbiota in rats significantly. Compared with the control and blank groups, the contents of caproic acid, isobutyric acid, isovaleric acid, and propanoic acid in the colon contents decreased in the male-BPA group (P < 0.05), and caproic acid, isobutyric acid, isovaleric acid, and valeric acid in the colon contents decreased in the female-BPA group (P < 0.05). Metabolomic analysis of the serum indicated that BPA could regulate bile acid levels, especially ursodeoxycholic acid (UDCA) and its conjugated forms. The contents of amino acids, hormones, and lipids were also significantly affected after exposure to BPA. The increase in interleukin-6 (IL-6), interleukin-23 (IL-23), and transforming growth factor-ß (TGF-ß) in the serum of the male-BPA group suggests that BPA exposure affects the immune system. Conclusion: BPA exposure will cause toxicity to rats via disrupting the gut-liver-hormone axis.

Value of Real-Time Shear Wave Elastography Versus Acoustic Radiation Force Impulse Imaging in the Diagnosis of Female Bladder Neck Obstruction.

OBJECTIVE: To investigate the application value of shear wave elastography (SWE) and acoustic radiation force impulse imaging (ARFI) in the diagnosis of female bladder neck obstruction (FBNO), we compared the advantages of these 2 methods to provide a more accurate reference for clinical work. METHODS: From April 2016 to February 2018, 27 patients who were diagnosed with FBNO by cystoscopy and/or urine dynamics testing were selected for the study, together with 24 healthy adults in a case-control study at Liaoning Province People's Hospital. We collected general information from 27 patients with FBNO, and using transperineal 2-dimensional ultrasound detection, shear wave elastography (SWE) and ARFI were used, respectively, to detect the Young's modulus and shear wave velocity (SWV) of the bladder necks. Cystoscopy results were considered to be the gold standard, and receiver operating characteristic (ROC) curves were drawn for ARFI, SWE, and the combined diagnosis of the two. The efficacy of the diagnosis was determined by comparing the areas under the ROC curves and calculating the sensitivity, specificity, and accuracy. RESULTS: The areas under the ROC curve for the Q-box mean and max value detected by SWE for FBNO patients were 88.4% and 89.9%, respectively, and the sensitivity, specificity, and accuracy were 81.5%, 79.2%, and 80.4%, respectively. The area under the ROC curve detected by ARFI for FBNO patients was 93.7%, and the sensitivity, specificity, and accuracy were 88.9%, 79.2%, and 84.3%, respectively. The sensitivity, specificity, and accuracy of the combined detection of ARFI and SWE were 92.5%, 87.5%, and 90.2%, respectively. The best diagnostic cutoff point of the SWV or the Q-box mean and max value of SWE in FBNO obtained with the ROC curve was SWV = 2.38 m/s (sensitivity, 71.4%; specificity, 82.5%), Q-box mean = 20.2 kPa, Q-box max = 39.8 kPa (sensitivity, 67.5%; specificity, 76.2%). The average shear wave velocity of ARFI, Q-box mean, and Q-box max value of SWE in the control group were 1.89 ± 0.35 m/s, 15.3 ± 3.6 kPa, and 29.2 ± 8.7 kPa, respectively. In the FBNO group, these values were 2.81 ± 0.63) m/s, 27.2 ± 8.6 kPa, and 51.2 ± 12.3 kPa, respectively. The differences were statistically significant (P < .05). CONCLUSION: The value of the ARFI in the diagnosis of FBNO is a little greater than that of SWE in terms of sensitivity and accuracy, and the combined detection of ARFI and SWE performs better than ARFI or SWE employed separately.

NVP-BKM120 inhibits colon cancer growth via FoxO3a-dependent PUMA induction.

NVP-BKM120, a potent and highly selective PI3K inhibitor, is currently being investigated in phase I/II clinical trials. The mechanisms of action of NVP-BKM120 in colon cancer cells are unclear. In the present study, we investigated how NVP-BKM120 suppresses colon cancer cells growth and potentiates effects of other chemotherapeutic drugs. We found that NVP-BKM120 treatment enhance PUMA induction irrespective of p53 status through the FoxO3a pathway following AKT inhibition. Furthermore, PUMA is required for NVP-BKM120-induced apoptosis in colon cancer cells. In addition, NVP-BKM120 also synergized with 5-Fluorouracil or regorafenib to induce marked apoptosis via PUMA induction. Deficiency of PUMA suppressed apoptosis and antitumor effect of NVP-BKM120 in xenograft model. These results demonstrate a key role of PUMA in mediating the anticancer effects of NVP-BKM120 and suggest that PUMA could be used as an indicator of NVP-BKM120 sensitivity, and also have important implications for it clinical applications.

Application of Acoustic Radiation Force Impulse Imaging for Diagnosis of Female Bladder Neck Obstruction.

OBJECTIVES: To determine the application value of combined transperineal sonography and Virtual Touch tissue quantification (Siemens Medical Solutions, Mountain View, CA) on acoustic radiation force impulse imaging as a scanning method for diagnosis of female bladder neck obstruction. METHODS: Transperineal sonography and Virtual Touch tissue quantification were combined to depict the bladder neck and observe its sonographic characteristics in 36 patients with female bladder neck obstruction and 30 healthy adults in a case-control study. We measured the thickness and shear wave velocity (SWV) of the bladder neck's anterior and posterior lips. RESULTS: There was a statistically significant difference in the thickness and SWV of the bladder neck between the healthy women and those with bladder neck obstruction, whose SWV was higher (P< .05). For the anterior lip, an SWV of 2.11 m/s was the best cutoff point for differentiating bladder neck obstruction from a normal bladder neck; for the posterior lip, an SWV of 2.06 m/s was the best cutoff point. The mean thicknesses of the anterior and posterior lips ± SD were 0.66 ± 0.05 and 0.68 ± 0.05 cm in the group with bladder neck obstruction versus 0.45 ± 0.07 and 0.52 ± 0.09 cm in the normal group. There was a significant difference between them (P < .05). CONCLUSIONS: The bladder neck's anatomic structure can be observed visually by perineal sonography. Virtual Touch tissue quantification on acoustic radiation force impulse imaging can quantitatively reflect the bladder neck stiffness and change in texture. It could provide a quantitative indicator for clinical diagnosis of female bladder neck obstruction and etiology research and display important clinical values.