Jian Gan powder ameliorates immunological liver injury in mice by modulating the gut microbiota and metabolic profiles.

BACKGROUND: Immunological liver injury (ILI) is a common liver disease associated with the microbiota-gut-liver axis. Jian Gan powder (JGP) exhibits both protective and therapeutic effects on hepatitis virus-induced ILI in the clinic. However, the underlying mechanisms remain elusive. The aim of this study is to investigate the hepatoprotective effects and associated mechanisms of JGP in the context of gut microbiota, utilizing a mouse model of ILI. METHODS: The mouse model was established employing Bacillus Calmette-Guérin (BCG) plus lipopolysaccharide (LPS). Following treatment with JGP (7.5, 15, or 30 g/kg), serum, liver, and fresh fecal samples were analyzed. 16S rRNA gene sequencing and untargeted metabolomics profiling were performed to assess the role of JGP on the gut microbiota and its metabolites. RESULTS: JGP treatment markedly reduced serum IFN-γ, IL-6, IL-22, and hepatic p-STAT3 (phosphorylated transducer and activator of transcription-3) expression. In contrast, JGP increased the percentage of proliferating cell nuclear antigen-positive liver cells in treated mice. Fecal 16S rRNA gene sequencing revealed that JGP treatment restored the levels of Alloprevotella, Burkholderia-Caballeronia-Paraburkholderia, Muribaculum, Streptococcus, and Stenotrophomonas. Additionally, metabolomics analysis of fecal samples showed that JGP restored the levels of allylestrenol, eplerenone, phosphatidylethanolamine (PE) (P-20:0/0:0), sphingomyelin (SM) d27:1, soyasapogenol C, chrysin, and soyasaponin I. CONCLUSIONS: JGP intervention improves ILI by restoring gut microbiota and modifying its metabolic profiles. These results provide a novel insight into the mechanism of JGP in treating ILI and the scientific basis to support its clinical application.

BART: A transferable liquid chromatography retention time library for bile acids.

Identification of unknown bile acids, especially the distinguishment between isomers, requires retention times of a large number of reference standards, which are often not commercially available. Meanwhile, published retention information cannot be directly transferred across labs due to the differences between liquid chromatography (LC) systems, such as different extra column volume and dwell volume. To improve this situation, a transferrable retention time library for bile acids named BART was developed. BART was composed of isocratic retention models of 272 bile acids and a software tool to predict their gradient retention times on various LC systems. The isocratic retention times of bile acids were acquired on a Waters BEH C18 column with mobile phases of acidic ammonium acetate buffer and acetonitrile, and fit to the quadratic solvent strength model (QSSM). Segmented linear gradient retention times were calculated with holdup time (t0), dwell time (tD) and actual gradient profile corrected using 21 bile acid calibration standards. In addition to the reference system where the isocratic retention times were acquired, this approach has been validated on four other LC-MS systems in four labs with two gradient methods. Average root mean square errors (RMSE) between predicted and experimental retention times were 0.052 and 0.054 min for the two gradients tested, which were 9-fold more accurate than referring to a static retention time library. The library is freely available at https://bafinder.github.io/.

Clinical efficacy of tetrandrine in artificial stone-associated silicosis: A retrospective cohort study.

Background: Outbreaks of silicosis have occurred among workers in the artificial stone (AS) industry, and there is currently no effective antifibrosis treatment for silicosis. Design: A retrospective cohort study. Methods: We retrospectively analyzed the clinical data of 89 artificial stone-associated silicosis patients treated in Shanghai Pulmonary Hospital (China). Patients who agreed to be administered tetrandrine entered the observation group and those who disagreed entered the control group. Changes in chest HRCT, pulmonary function, and clinical symptoms of patients in two groups were compared pre- and post-treatment. Results: After treatment for 3-12 months, 56.5%-65.4% of patients in the observation group showed improvements in HRCT imaging, while there was no improvement in the control group (p < 0.05). Disease progression occurred in 0%-17.4% of patients in the observation group after 3-12 months of treatment compared with 44.4%-92.0% of patients in the control group (p < 0.05). After 3 months of treatment, the forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and diffusing capacity of the lung for carbon monoxide (DLco) in the observation group increased by 136.7 ± 189.2 mL (p < 0.05), 124.2 ± 169.9 mL (p < 0.05), and 1.4 ± 2.3 mL/min/mmHg (p > 0.05), respectively, while those in the control group decreased (145.8 ± 356.5; 107.5 ± 272.1; 1.9 ± 3.8). After 6 months of treatment, FVC, FEV1, and DLco in the observation group increased by 207.8 ± 372.2 mL (p > 0.05), 107.8 ± 295.2 mL (p > 0.05) and 0.7 ± 6.0 mL/min/mmHg (p > 0.05), respectively, while those of the control group decreased (383.3 ± 536.7; 215.6 ± 228.9; 1.4 ± 1.7). The incidences of clinical symptoms such as cough, expectoration, dyspnea, chest tightness, and chest pain in the observation group were decreased-after treatment (all p < 0.05), while the incidences of these symptoms increased in the control group, although the change was not statistically significant (all p > 0.05). Conclusion: Tetrandrine can control and delay the progression of AS-associated silicosis fibrosis, with improved chest HRCT imaging and pulmonary function.

Risk Factors of Silicosis Progression: A Retrospective Cohort Study in China.

Background: Silicosis poses a threat to workers' health due to the irreversible lung lesions. Design: A retrospective cohort study. Methods: A total of 259 patients [80 worked with artificial stone (AS), 179 with non-artificial stone (non-AS)] with confirmed silicosis were included in this study. Forty-one of AS and 91 of non-AS had approximately 2 years' follow-up records [lung function tests and high-resolution computer tomography (HRCT)]. Compared with the first records, increased, densified, or newly emerging lesions in lung HRCT images were judged as progression of the disease. Cox proportional hazards models were used to determine the risk factors. Kaplan-Meier survival curve and log-rank test were used to compare prognostic factors for cumulative risk of progression. Results: In 132 patients with median follow-up of 24.0 months (IQR, 13.8, 24.9), 66 patients showed progression, in them, 36 (87.8%) were from AS group and 30 (32.9%) from non-AS group. Working experience of AS processing (hazard ratio, 5.671; 95% CI, 3.048-10.550) and complicated silicosis in CT images (hazard ratio, 2.373; 95% CI, 1.379-4.082) were the main risk factors associated with progression. Forced vital capacity decreased after 1-year (241.5 vs. 55.2 mL) and 2-year (328.1 vs. 68.8 mL) follow-up in the two groups (AS vs. non-AS). History of anti-tuberculosis medication, chest oppression and pain, ground-glass opacity, pleural abnormalities, and restrictive pulmonary dysfunction were more frequently found on HRCT images in the AS group than non-AS group. Lung functions (DLCO, %) were lower in the current/former smokers than the non-smokers (P < 0.05) in AS patients. Conclusion: Prevention and protection rules are needed to be enforced in the occupation involving AS processing; smoking may be associated with declined lung function in AS patients.

Typing and determination of SNP functional gene based on highly selective and signal-amplified fluorescence double-probe with the help of ExoIII nuclease and magnetic bead.

We have developed a fluorescence double-probe detection system with signal amplification for simple typing and determination of single nucleotide polymorphism (SNP) functional gene based on non-sequence dependence of ExoIII nuclease on dsDNA and rapid separation of magnetic bead. Matched detected gene can cyclically release abundant fluorescence-labeled ssDNA from the probe and the corresponding measured fluorescence signal is amplified up to 6063 times. In this case, the probe cannot release the measured fluorescence signal for the point mutation gene and then the corresponding measured signal is inhibited. According to signal amplification and inhabitation of the probe, we proposed both an accurate genotyping approach with strong specificity and a sensitive determination approach with high selectivity for SNP functional gene. For qualitative genotyping, there are obvious genotype-based differences of measured fluorescence phenotypes among three kinds of the samples of the investigated SNP. The quantitative determinations of its wild-type gene and mutant gene have all a good linearity in the range from 0.5 to 500 pmol/L with the correlation coefficients R2 of 0.9940 and 0.9911, and a high sensitivity with the detection limits of 0.11 and 0.20 pmol/L, respectively. Compared to the usual single-probe detection system, the developed double-probe system can achieve not only accurate genotyping but also the sensitive gene determination. Meanwhile, it is also a simple and reliable method for both quantitative and qualitative analysis of functional gene.

Identification, isolation, characterization, and UHPLC quantification of potential genotoxic impurities in linagliptin.

During the stress testing of linagliptin, one unknown degradation product (impurity I) on acidic conditions was detected by using high-performance liquid chromatography and subsequently isolated, identified, and characterized by the spectral data (MS, MS/MS, 1D and 2D NMR spectroscopy, and IR spectroscopy) and finally subjected for mechanism analysis. The degradation product (impurity I) and another process-related impurity (impurity II) of linagliptin were found to contain the structural alerts of N-acylated aminoaryl and alkyl halide, respectively, which were both potential genotoxic substances. Hence, a rapid and facile ultra high performance liquid chromatography method was developed for the simultaneous determination of these two potential genotoxic impurities at ppm levels in linagliptin. The factors involved in the method development were discussed and this method was fully validated as per International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines, which proved the method sensitive, selective, and robust. The presented method has been successfully applied to the analysis of real samples from multiple batches. This study will help to risk management of possible genotoxic impurities present in linagliptin.

The protective effects of Sauropus spatulifolius on acute lung injury induced by lipopolysaccharide.

BACKGROUND: Sauropus spatulifolius Beille (named 'Long-Li-Ye' in China) is used to make 'herbal tea' to prevent pneumonia. This study aimed to evaluate the antioxidant activities in vitro and the protective effects of Long-Li-Ye on acute lung injury (ALI) induced by lipopolysaccharide (LPS). RESULTS: The supernatant after ethanol addition to Long-Li-Ye water extract (LLYCSL) and the resin eluting fraction of LLYCSL (LLY40) showed strong antioxidant activities in vitro. LLYCSL and LLY40 could attenuate ALI via decreasing myeloperoxidase activity, increasing superoxide dismutase activity and decreasing the levels of tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß) and IL-6. In addition, LLY40 could increase catalase activity, increase the levels of IL-10, IL-4 and IL-13 and decrease the TNF-α/IL-10 ratio. CONCLUSION: Long-Li-Ye could be used as a natural antioxidant for food production and functional food or dietary supplementation for people with ALI. © 2018 Society of Chemical Industry.

Enrichment and antioxidant properties of flavone C-glycosides from trollflowers using macroporous resin.

Orientin, vitexin and other flavone C-glycosides are functional ingredients abundant in trollflowers. In this study, an efficient method for enrichment of these ingredients from the flowers of Trollius chinensis Bunge was developed using macroporous resin. Separation characteristics of six typical macroporous resins were investigated by static adsorption/desorption and dynamic separation experiments, and HPD450 was selected as optimal one. Dynamic adsorption/desorption experiments on HPD450 columns were conducted to obtain the optimal parameters, followed by a scale-up experiment. Six fractions, TC-1-TC-3 together with their acid hydrolysates were further prepared to evaluate their antioxidant capacities by 2,2-diphenyl-1-picrylhydrazyl radical and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonate) radical cation scavenging assays. They all have notable concentration-dependent antioxidant activities, with TC-1 showing strong antioxidant capacity higher than orientin. The separation process was high-efficient, low-cost and environmental-friendly, which could afford a potential approach for industrial applications.