Analysis of Chemical Constituents of Miao Ethnomedicine Heiguteng Zhuifeng Huoluo Capsule (HZFC) and the Discovery of Active Substances in the Treatment of Rheumatoid Arthritis.

In this study, the chemical substances of Heiguteng Zhuifeng Huoluo Capsule (HZFC) and its potential active ingredients for the treatment of rheumatoid arthritis (RA) were characterized and analyzed by medicinal chemistry combined with bioinformatics methods. Also, the potential active ingredients of HZFC against RA were verified by lipopolysaccharide (LPS)-induced macrophage activation model. The results showed that 79 chemical constituents were successfully identified, mainly including phenylpropanoids, flavonoids, and alkaloids. Among them, 13 active components were closely related to the nine core targets (FASN, ALOX5, EGFR, MMP1, CYP2D6, CNR1, AR, MAOA, and FKBP5) of HZFC in the treatment of RA. Molecular docking further proved that 13 active components had strong docking activity with 9 core targets. In the verification experiment of the LPS-induced RAW 264.7 macrophage model, the verified components (magnoflorine, N-feruloyltyramine, canadine, rutin, quercetin-3-O-glucoside, and pseudocolumbamine) all showed a clear inhibitory effect on the secretion of inflammatory factors in model cells. The above research results suggest that 13 components such as stepharanine, rutin, quercetin-3-O-glucoside, corydine methyl ether, canadine, 8-oxoepiberberine, disinomenine, deosinomenine glucoside, tuduranine, magnoflorine, isosinomenine, pseudocolumbamine, and N-feruloyltyramine may be the main active substances of HZFC in the treatment of RA.

Research progress on molecular biomarkers of acute myeloid leukemia.

Acute myeloid leukemia (AML) is the most common type of adult acute leukemia. The pathophysiology of the disease has been studied intensively at the cellular and molecular levels. At present, cytogenetic markers are an important basis for the early diagnosis, prognostic stratification and treatment of AML. However, with the emergence of new technologies, the detection of other molecular markers, such as gene mutations and epigenetic changes, began to play important roles in evaluating the occurrence and development of diseases. Recent evidence shows that identifying new AML biomarkers contributes to a better understanding of the molecular mechanism of the disease and is essential for AML screening, diagnosis, prognosis monitoring, and individualized treatment response. In this review, we summarized the promising AML biomarkers from four aspects, which contributing to a better understanding of the disease. Of course, it must be soberly aware that we have not listed all biomarkers of AML. Anyway, the biomarkers we mentioned are representative. For example, mutations in TP53, FLT3, and ASXL1 suggest poor prognosis, low remission rate, short survival period, and often require allogeneic hematopoietic stem cell transplantation. The CEBPA double mutation, NPM1 and CBF mutation suggest that the prognosis is good, the remission rate is high, the survival period is long, and the effect of chemotherapy or autotherapy is good. As for other mutations mentioned in the article, they usually predict a moderate prognosis. All in all, we hope it could provide a reference for the precise diagnosis and treatment of AML.

Untargeted metabolomics characteristics of nonobese nonalcoholic fatty liver disease induced by high-temperature-processed feed in Sprague-Dawley rats.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases in the world. In our early clinical data and questionnaire analysis of NAFLD, it was found that the body mass index of some patients did not meet the diagnostic criteria for overweight or obesity. The consumption of high-temperature-processed foods such as fried food, hot pot and barbecue is closely related to the occurrence of nonobese NAFLD. Reducing the intake of this kind of food can reduce disease severity and improve prognosis. AIM: To explore the untargeted metabolomics characteristics of nonobese nonalcoholic fatty liver disease in Sprague-Dawley rats induced by high-temperature-processed feed. METHODS: Fifty-four male Sprague-Dawley rats were divided into three groups: The control group received a standard diet; the nonfried soybeans (NDFS) group received 60% NDFS and 40% basic feed and the dry-fried soybeans (DFS) group received 60% DFS and 40% basic feed. Six rats were sacrificed at week 4, 8, and 12 in each group. The food intake, body weight, Lee's index, liver index, serological index and hepatic histopathology were assessed. Untargeted metabolomics characteristics were used to analyze the changes in liver metabolites of rats at week 12. Correlations between metabolites and pathology scores between the DFS and control groups and between the DFS and NDFS groups were analyzed. We selected some of the metabolites, both within the pathway and outside of the pathway, to explain preliminarily the difference in liver pathology in the three groups of rats. RESULTS: There were no statistically significant differences in the food intake, body weight, Lee's index or serological index between the DFS group and the control group (P > 0.05). At week 8 and week 12, the steatosis scores in the DFS group were significantly higher than those in the other two groups (P < 0.05). At week 12, the liver index of the DFS group was the lowest (NDFS group vs DFS group, P < 0.05). The fibrosis score in the DFS group was significantly higher than those in the other two groups (P < 0.05). The correlation analysis of the liver pathology score and differential metabolites in the DFS and NDFS groups showed that there were 10 strongly correlated substances: Five positively correlated substances and five negatively correlated substances. The positively correlated substances included taurochenodeoxycholate-3-sulfate, acetylcarnitine, 20a,22b-dihydroxycholesterol, 13E-tetranor-16-carboxy-LTE4 and taurocholic acid. The negatively correlated substances included choline, cholesterane-3,7,12,25-tetrol-3-glucuronide, nicotinamide adenine dinucleotide phosphate, lysoPC [16:1 (9Z)] and glycerol 3-phosphate. The correlation analysis of the liver pathology score and differential metabolites in the DFS and control groups showed that there were 13 strongly correlated substances: Four positively correlated substances and 9 negatively correlated substances. The positively correlated substances included 4-hydroxy-6-eicosanone, 3-phosphoglyceric acid, 13-hydroxy-9-methoxy-10-oxo-11-octadecenoic acid and taurochenodeoxycholate-3-sulfate. The negatively correlated substances included lysoPC [16:1(9Z)], S-(9-hydroxy-PGA1)-glutathione, lysoPC [20:5 (5Z, 8Z, 11Z, 14Z, 17Z)], SM (d18:1/14:0), nicotinamide adenine dinucleotide phosphate, 5,10-methylene-THF, folinic acid, N-lactoyl-glycine and 6-hydroxy-5-methoxyindole glucuronide. CONCLUSION: We successfully induced liver damage in rats by using a specially prepared high-temperature-processed feed and explored the untargeted metabolomics characteristics.

Altered profiles of fecal metabolites correlate with visceral hypersensitivity and may contribute to symptom severity of diarrhea-predominant irritable bowel syndrome.

BACKGROUND: Fecal metabolites are associated with gut visceral sensitivity, mucosal immune function and intestinal barrier function, all of which have critical roles in the pathogenesis of irritable bowel syndrome (IBS). However, the metabolic profile and pathophysiology of IBS are still unclear. We hypothesized that altered profiles of fecal metabolites might be involved in the pathogenesis of IBS with predominant diarrhea (IBS-D). AIM: To investigate the fecal metabolite composition and the role of metabolites in IBS-D pathophysiology. METHODS: Thirty IBS-D patients and 15 age- and sex-matched healthy controls (HCs) underwent clinical and psychological assessments, including the IBS Symptom Severity System (IBS-SSS), an Italian modified version of the Bowel Disease Questionnaire, the Bristol Stool Form Scale (BSFS), the Hospital Anxiety and Depression Scale, and the Visceral Sensitivity Index. Visceral sensitivity to rectal distension was tested using high-resolution manometry system by the same investigator. Fecal metabolites, including amino acids and organic acids, were measured by targeted metabolomics approaches. Correlation analyses between these parameters were performed. RESULTS: The patients presented with increased stool water content, more psychological symptoms and increased visceral hypersensitivity compared with the controls. In fecal metabolites, His [IBS-D: 0.0642 (0.0388, 0.1484), HC: 0.2636 (0.0780, 0.3966), P = 0.012], Ala [IBS-D: 0.5095 (0.2826, 0.9183), HC: 1.0118 (0.6135, 1.4335), P = 0.041], Tyr [IBS-D: 0.1024 (0.0173, 0.4527), HC: 0.5665 (0.2436, 1.3447), P = 0.018], Phe [IBS-D: 0.1511 (0.0775, 0.3248), HC: 0.3967 (0.1388, 0.7550), P = 0.028], and Trp [IBS-D: 0.0323 (0.0001, 0.0826), HC: 0.0834 (0.0170, 0.1759), P = 0.046] were decreased in IBS-D patients, but isohexanoate [IBS-D: 0.0127 (0.0060, 0.0246), HC: 0.0070 (0.0023, 0.0106), P = 0.028] was significantly increased. Only Tyr was mildly correlated with BSFS scores in all subjects (r = -0.347, P = 0.019). A possible potential biomarker panel was identified to correlate with IBS-SSS score (R 2 Adjusted = 0.693, P < 0.001). In this regression model, the levels of Tyr, Val, hexanoate, fumarate, and pyruvate were significantly associated with the symptom severity of IBS-D. Furthermore, visceral sensation, including abdominal pain and visceral hypersensitivity, was correlated with isovalerate, valerate and isohexanoate. CONCLUSION: Altered profiles of fecal metabolites may be one of the origins or exacerbating factors of symptoms in IBS-D via increasing visceral sensitivity.

Optimization of liquid-state fermentation conditions for the glyphosate degradation enzyme production of strain Aspergillus oryzae by ultraviolet mutagenesis.

This study aimed to obtain strains with high glyphosate-degrading ability and improve the ability of glyphosate degradation enzyme by the optimization of fermentation conditions. Spore from Aspergillus oryzae A-F02 was subjected to ultraviolet mutagenesis. Single-factor experiment and response surface methodology were used to optimize glyphosate degradation enzyme production from mutant strain by liquid-state fermentation. Four mutant strains were obtained and named as FUJX 001, FUJX 002, FUJX 003, and FUJX 004, in which FUJX 001 gave the highest total enzyme activity. Starch concentration at 0.56%, GP concentration at 1,370 mg/l, initial pH at 6.8, and temperature at 30°C were the optimum conditions for the improved glyphosate degradation endoenzyme production of A. oryzae FUJX 001. Under these conditions, the experimental endoenzyme activity was 784.15 U/100 ml fermentation liquor. The result (784.15 U/100 ml fermentation liquor) was approximately 14-fold higher than that of the original strain. The result highlights the potential of glyphosate degradation enzyme to degrade glyphosate.

Gold embedded maghemite hybrid nanowires and their gas sensing properties.

Well-defined gold embedded maghemite hybrid nanowires are synthesized, and their structures are fully characterized. They are composed of porous γ-Fe2O3 shells and embedded gold nanoparticles (3-10 nm), which is novel and very different from the conventional "surface decoration" configuration. These hybrid nanowires are produced by the de-alloying of Au-Fe alloy nanowires and subsequent heat treatment. The reaction mechanism is proposed and validated. The results of X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and thermogravimetry techniques prove consistently that the Fe composition of Au-Fe alloy nanowires change to γ-FeOOH first and then to γ-Fe2O3. The embedded gold particles are help to enhance the gas response properties of the hybrid nanowires, which is attributed to the nano open-circuit Schottky junctions between γ-Fe2O3 and the Au nanoparticles. The gas sensing experiment data with high repeatability demonstrate that these hybrid nanowires are excellent sensing materials, especially for ethanol, and have shown both high selectivity and high sensitivity.