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The radiation-induced inflammatory response is involved in radiation damage to the cochlea and causes sensorineural hearing loss (SNHL). NF-κB, as the master switch of the inflammatory response, regulates the expression of many inflammation-related genes and thus the inflammatory response. Therefore, in this study we used a mouse model to determine whether radiation-induced NF-κB activation is involved in damage to the cochlea and to investigate the underlying mechanism. Eventually, we found that NF-κB was activated after radiation of the cochleae and the activation reached a maximum at 2–6 h after radiation. And morphological analysis showed severe damage to the cochleae after radiation, but this damage was significantly ameliorated by JSH-23 (an inhibitor of NF-κB) pretreatment. Along with these morphological changes, the expression levels of proinflammatory molecules (including proinflammatory cytokines IL-6, TNF-α, COX-2 and inflammation-related proteins VCAM-1, MIP-1β) in the cochlear tissues were significantly increased after radiation, but were significantly decreased by JSH-23 pretreatment compared to radiation alone. Therefore, these results indicated that radiation-induced NF-κB activation was involved in damage to the cochleae and resultant SNHL via its promotion of the inflammatory response mediated by overexpression of some proinflammatory molecules in cochlear tissues, and inhibition of radiation-induced NF-κB was conducive to preventing such damage. [ABSTRACT FROM AUTHOR]

Glycyrrhetinic acid (GA) is an anti-inflammatory drug with potential for development. However, the poor solubility of GA in water leads to extremely low bioavailability, which limits its clinical applications. Solid dispersions have become some of the most effective strategies for improving the solubility of poorly soluble drugs. Soluplus®, a non-cytotoxic amphiphilic solubilizer, significantly improves the solubility of BCS II drugs and improves the bioavailability of insoluble drugs. l-arginine (L-Arg) can be used as a small molecular weight excipient to assist in improving the solubility of insoluble drugs. In this study, we developed a new formulation for oral administration by reacting GA and L-Arg to form salts by co-solvent evaporation and then adding the polymer-solvent Soluplus® with an amphiphilic chemical structure to prepare a solid dispersion GA-SD. The chemical and physical properties of GA-SD were characterized by DLS, TEM, XRD, FT-IR and TG. The anti-inflammatory activity of GA-SD was verified by LPS stimulation of RAW 267.5 cells simulating a cellular inflammation model, TPA-induced ear edema model in mice, and ethanol-induced gastric ulcer model. The results showed that the amide bond and salt formation of GA-SD greatly improved GA solubility. GA-SD effectively improved the anti-inflammatory effect of free GA in vivo and in vitro, and GA-SD had no significant effect on liver and kidney function, no significant tissue toxicity, and good biosafety. In conclusion, GA-SD with L-Arg and Soluplus® is an effective method to improve the solubility and bioavailability of GA. As a safe and effective solid dispersion, it is a promising anti-inflammatory oral formulation and provides some references for other oral drug candidates with low bioavailability. [ABSTRACT FROM AUTHOR]

Limited knowledge of the long‐term effects of excessive iodine (EI) intake on biomolecular signatures in the liver/pancreas/kidney prompted this study. Herein, following 6 months of exposure in mice to 300, 600, 1200 or 2400 μg/L iodine, the biochemical signature of alterations to the liver/pancreas/kidney was profiled using attenuated total reflection Fourier‐transform infrared (ATR‐FTIR) spectroscopy coupled with principal component analysis‐linear discriminant analysis (PCA‐LDA). Our research showed that serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), serum creatinine (Scr), insulin, blood glucose levels and homeostasis model assessment for insulin resistance (HOMA‐IR) index in the 1200 and 2400 μg/L iodine‐treated groups were significantly increased compared with those in the control group. Moreover, histological analysis showed that the liver/kidney/pancreas tissues of mice exposed to EI treatment displayed substantial morphological abnormalities, such as a loss of hepatic architecture, glomerular cell vacuolation and pancreatic neutrophilic infiltration. Notably, EI treatment caused distinct biochemical signature segregation between EI‐exposed versus the control liver/pancreas/kidney. The main biochemical alterations between EI‐exposed and control groups were observed for protein phosphorylation, protein secondary structures and lipids. The ratios of amide I‐to‐amide II (1674 cm−1/1570 cm−1), α‐helix‐to‐β‐sheet (1657 cm−1/1635 cm−1), glycogen‐to‐phosphate (1030 cm−1/1086 cm−1) and the peptide aggregation (1 630 cm−1/1650 cm−1) level of EI‐treated groups significantly differed from the control group. Our study demonstrated that EI induced hepatic, renal and pancreatic injury by disturbing the structure, metabolism and function of the cell membrane. This finding provides the new method and implication for human health assessment regarding long‐term EI intake. Chronic excessive iodine (EI) intake is capable of inducing hepatic, renal, and pancreatic injury. Exposure to EI led to a series of biochemical changes, including alterations in protein phosphorylation, protein secondary structures, and lipids, which potentially affect cellular metabolism and physiology. ATR‐FTIR spectroscopy shows a great ability to detect EI‐induced biochemical changes that impair cellular function in target organs [ABSTRACT FROM AUTHOR]

The total alkaloids extracted from the seeds of Sophora moorcroftiana (TAs-SM) have the potential to treat alveolar echinococcosis, a disease included by the WHO in a list of 17 key neglected diseases world-wide. The aims of the current study were first to develop a supercritical fluid extraction (SFE) method for optimizing TAs-SM extraction, and second, to develop an optimized method for evaluating TAs-SM pharmacokinetics in vivo. The Box–Behnken response surface method was used to optimize the extraction process, and ultra-high liquid chromatography coupled with high resolution electrospray mass spectrometry (UPLC-HR-ESI-MS) was used to determine the pharmacokinetics of TAs-SM in SD rats. The results indicated the following optimal SFE extraction conditions: pressure = 31 MPa, temperature = 70 °C, time = 162.18 min. With these parameters, total alkaloids could be extracted from each gram of S. moorcroftiana, with the total content being 68.88 μg. The linear range of UPLC-HR-ESI-MS is 0.78–200.00 ng/ml, R2 > 0.99, and the sample recovery is 99–113%. The precision, accuracy, selectivity and stability of the method meet the requirements of US FDA guidelines. To our knowledge this study is the first to establish an SFE method for extracting TAs-SM and the first to employ UPLC-HR-ESI-MS for measuring TAs-SM in rats. These findings provide important contributions for using TAs-SM in further drug development and clinical applications. [ABSTRACT FROM AUTHOR]