Bioactive compounds from Huashi Baidu decoction possess both antiviral and anti-inflammatory effects against COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global health concern, and effective antiviral reagents are urgently needed. Traditional Chinese medicine theory-driven natural drug research and development (TCMT-NDRD) is a feasible method to address this issue as the traditional Chinese medicine formulae have been shown effective in the treatment of COVID-19. Huashi Baidu decoction (Q-14) is a clinically approved formula for COVID-19 therapy with antiviral and anti-inflammatory effects. Here, an integrative pharmacological strategy was applied to identify the antiviral and anti-inflammatory bioactive compounds from Q-14. Overall, a total of 343 chemical compounds were initially characterized, and 60 prototype compounds in Q-14 were subsequently traced in plasma using ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry. Among the 60 compounds, six compounds (magnolol, glycyrrhisoflavone, licoisoflavone A, emodin, echinatin, and quercetin) were identified showing a dose-dependent inhibition effect on the SARS-CoV-2 infection, including two inhibitors (echinatin and quercetin) of the main protease (Mpro), as well as two inhibitors (glycyrrhisoflavone and licoisoflavone A) of the RNA-dependent RNA polymerase (RdRp). Meanwhile, three anti-inflammatory components, including licochalcone B, echinatin, and glycyrrhisoflavone, were identified in a SARS-CoV-2-infected inflammatory cell model. In addition, glycyrrhisoflavone and licoisoflavone A also displayed strong inhibitory activities against cAMP-specific 3',5'-cyclic phosphodiesterase 4 (PDE4). Crystal structures of PDE4 in complex with glycyrrhisoflavone or licoisoflavone A were determined at resolutions of 1.54 Å and 1.65 Å, respectively, and both compounds bind in the active site of PDE4 with similar interactions. These findings will greatly stimulate the study of TCMT-NDRD against COVID-19.

Chromosome-level assembly of the Neolamarckia cadamba genome provides insights into the evolution of cadambine biosynthesis.

Neolamarckia cadamba (Roxb.), a close relative of Coffea canephora and Ophiorrhiza pumila, is an important traditional medicine in Southeast Asia. Three major glycosidic monoterpenoid indole alkaloids (MIAs), cadambine and its derivatives 3ß-isodihydrocadambine and 3ß-dihydrocadambine, accumulate in the bark and leaves, and exhibit antimalarial, antiproliferative, antioxidant, anticancer and anti-inflammatory activities. Here, we report a chromosome-scale N. cadamba genome, with 744.5 Mb assembled into 22 pseudochromosomes with contig N50 and scaffold N50 of 824.14 Kb and 29.20 Mb, respectively. Comparative genomic analysis of N. cadamba with Co. canephora revealed that N. cadamba underwent a relatively recent whole-genome duplication (WGD) event after diverging from Co. canephora, which contributed to the evolution of the MIA biosynthetic pathway. We determined the key intermediates of the cadambine biosynthetic pathway and further showed that NcSTR1 catalyzed the synthesis of strictosidine in N. cadamba. A new component, epoxystrictosidine (C27H34N2O10, m/z 547.2285), was identified in the cadambine biosynthetic pathway. Combining genome-wide association study (GWAS), population analysis, multi-omics analysis and metabolic gene cluster prediction, this study will shed light on the evolution of MIA biosynthetic pathway genes. This N. cadamba reference sequence will accelerate the understanding of the evolutionary history of specific metabolic pathways and facilitate the development of tools for enhancing bioactive productivity by metabolic engineering in microbes or by molecular breeding in plants.

Hospitalization for cancer among radiologists in Taiwan.

BACKGROUND: Population aging and the incremental use of high-tech instruments increase the demand for radiological examinations and treatments in medical services. The exposure of radiologists and other medical workers to medical treatment radiation may thus be increased. OBJECTIVES: The aim of the study was to explore the average number of cancer hospitalizations and use of hospitalization as cancer treatment for radiologists compared with that for family medicine physicians, as well as the trends in the annual average number of cancer hospitalizations among radiologists. METHODS: Research data were obtained from the 2000-2010 Taiwan National Health Insurance Research Database. These samples collected for this study were unbalanced panel data. RESULTS: The average number of cancer hospitalizations for radiologists from 2000 to 2010 ranged between 3.67 and 28.26‰. After controlling the effects of gender, age, hospital accreditation level and year using generalized estimating equations with a binomial distribution and logit link function, our study found that radiologists had non significant higher risk of cancer hospitalizations compared with family medicine physicians. However, the average number of cancer hospitalizations for radiologists showed an annual decline from 2000 to 2010. CONCLUSIONS: Compared with family medicine physicians, radiologists had non significant higher risk of cancer hospitalizations. The data period examined in this study was only 11 years. Considering the numerous new radiological procedures currently in use in modern medical treatments, the health status of medical radiation workers should be continuously monitored in the future.

Risk of nonpsychotic mental disorders development in antiviral-treated mentally healthy chronic hepatitis C patients: A population-based study.

BACKGROUND/PURPOSE: Interferon (IFN) is able to induce significant psychiatric side effects in chronic hepatitis C (CHC) patients, whereas the risk of nonpsychotic mental disorder (NPMD) development in antiviral-treated mentally healthy CHC patients remains obscure. We used a population-based study to assess the risk of NPMD development in patients who had undergone antiviral treatment compared with untreated chronic hepatitis C virus (HCV)-infected and nonalcoholic fatty liver disease (NAFLD) patients. METHODS: Data were retrieved from Taiwan's National Health Insurance Research Database cohort consisting of 1 million individuals for a longitudinal analysis. A total of 313 mentally healthy CHC patients who received IFN-based antiviral therapy were recruited and compared with those without antiviral therapy and NAFLD patients. The Chi-square test was used to obtain the hazard ratio and 95% confidence interval. RESULTS: Among the 313 CHC patients receiving pegylated interferon/ribavirin therapy, 62 patients (19.8%) were associated with NPMD. In the comparison cohort, composed of 313 age- and sex-matched CHC patients not receiving antiviral therapy, 70 patients (22.4%) were associated with NPMD. The Chi-square analysis revealed that antiviral therapy was not significantly associated with NPMD. The diagnosis of HCV-infected hepatitis was independently associated with NPMD when compared with NAFLD. The hazard ratio was 1.67 (95% confidence interval, 1.11-2.52; p = 0.018). Furthermore, generalized anxiety disorder was specifically higher in HCV-infected patients than those with NAFLD. CONCLUSION: Patients with HCV infection are at high risk of developing NPMD with or without IFN-based therapy.

Transesterification of rapeseed oil for biodiesel production in trickle-bed reactors packed with heterogeneous Ca/Al composite oxide-based alkaline catalyst.

A conventional trickle bed reactor and its modified type both packed with Ca/Al composite oxide-based alkaline catalysts were studied for biodiesel production by transesterification of rapeseed oil and methanol. The effects of the methanol usage and oil flow rate on the FAME yield were investigated under the normal pressure and methanol boiling state. The oil flow rate had a significant effect on the FAME yield for the both reactors. The modified trickle bed reactor kept over 94.5% FAME yield under 0.6 mL/min oil flow rate and 91 mL catalyst bed volume, showing a much higher conversion and operational stability than the conventional type. With the modified trickle bed reactor, both transesterification and methanol separation could be performed simultaneously, and glycerin and methyl esters were separated additionally by gravity separation.

Effect of calcination temperature on the activity of solid Ca/Al composite oxide-based alkaline catalyst for biodiesel production.

A solid Ca/Al composite oxide-based alkaline catalyst containing Ca(12)Al(14)O(33) and CaO was prepared by chemical synthesis and thermal activation from sodium aluminate solution and calcium hydroxide emulsion. The effect of calcination temperatures ranging from 120 °C to 1000 °C on activity of the catalyst was investigated. The catalyst calcined at 600 °C showed the highest activity with >94% yield of fatty acid methyl esters (i.e. biodiesel) when applied to the transesterification of rapeseed oil at a methanol:oil molar ratio of 15:1 at 65 °C for 3h. Structure and properties of the catalyst were studied and the characterizations with XRD, TGA, FTIR, BET, and SEM demonstrated that the performance of the catalyst was closely related to its specific surface area and crystalline structure. In particular, the generation of crystalline Ca(12)Al(14)O(33) improved the catalytic activity due its synergistic effect with CaO.

[Establishment of two-dimensional electrophoresis system of caudal gland].

OBJECTIVE: To establish an effective separation system of 2-DE for the proteome of caudal gland, and provide foundation for revealing the mechanisms of histological development and pharmacological activities. METHOD: The total proteins of caudal gland were extracted by TCA/acetone precipitation, phenol extraction/methanol-ammonium acetate precipitation and trizol-base method respectively and separated by immobilized pH gradient (IPG) strips prior to SDS-PAGE. Loading protein sample size and isoelectric focusing conditions were optimized. The gels were stained with Coomassie brilliant blue, scanned and then analyzed using PDQuest 8.0 analysis software. RESULT: The total proteins of caudal gland extracted by trizol-base method were the highest quality and could meet the needs of 2-DE. With 300 microg of proteins loaded on 7 cm pH 3-10 IPG strip followed by isoelectric focusing program II ,a satisfying 2-DE profiles were obtained. The total number of disticted protein spots was 209 with the optimized system. CONCLUSION: A well-resolved 2-DE patterns of caudal gland were obtained by this optimized system. This method could be applied to prepare other similar tissue sample and 2-DE studies.

[Extraction of lobetyolin from codonopsis with supercritical CO2].

OBJECTIVE: To develop a green and rapid method for extraction of lobetyolin from C. pilosula. METHOD: Extraction of lobetyolin from C. pilosula with supercritical carbon dioxide in the presence of ethanol was studied. The effects of pressure, temperature, volume of cosolvent and extraction time on efficiency and their interactive relationships were discussed, based on central composite design and response surface methodology (RSM). RESULT: The key effect factor was volume of cosolvent. The extraction yield of lobetyolin was 0.078 6 mg x g(-1) when C. pilosula (40-60 mesh) was extracted at 30 MPa, 60 degrees C and 2 L x min(-1) (as CO2 in normal pressure and temperature) for 100 minutes with supercritical CO2 and 1 mL x min(-1) ethanol as dynamic cosolvent. CONCLUSION: This result is better than that obtained from traditional method. Therefore, the optimized process is valuable for extraction of lobetyolin from C. pilosula.

[Extraction of sex hormone from antler velvet with supercritical CO2].

OBJECTIVE: To study the method of extraction of sex hormone from antler velvet with supercritical CO2. METHOD: Supercritical fluid extraction (SFE) was used to extract sex hormone from antler velvet and radioimmunoassay (RIA) was used to analyze the extracts. The chemical compositions in extracts were identified by GC-MS, TLC and HPLC, respectively. RESULT: The experimental results indicated that the extraction yield was 1.56% when 85% ethanol was used as co-solvent at temperature of 65 degrees C and extraction pressure of 30 MPa. Estradiol and progesterone in the extracts were 3.07, 776.18 ng x g(-1) respectively. CONCLUSION: It is feasible to extract hormone from antler velvet with supercritical CO2.

[Study on chromatographic fingerprint of extractive from Tripterygium wilfordii with supercritical carbon dioxide].

OBJECTIVE: To establish the chromatographic fingerprint of supercritical carbon dioxide extract of Tripterygium wilfordii. METHOD: HPLC method was applied for quality assessment of T. Wilfordii, HPLC analysis was performed on Kromasil C18 (4. 6 mm x 250 mm, 5 microm) with the mixture of acetonitrile-1% per thousand H3PO4, as mobile phase in gradient mode. The samples were detected at UV of 267 nm with column temperature of 35 degrees C, analytic time was 80 min; Flow-rate was 1.0 mL x min(-1). The chromatographic fingerprint of ten batches of samples was determined, for establishing the chromatographic fingerprint of T. Wilfordii. RESULT: Indicating 27 peaks in common, identified 21 peaks with chemical reference and HPLC-MS, and the HPLC fingerprint was established. CONCLUSION: The method is steady and accurate with a good repeatability and can be used as a quality control method for T. Wilfordii.

[Preparation of liposomes containing extracts of Tripterygium wilfordii and evaluation of its stability].

OBJECTIVE: The liposomes containing extracts of Tripterygium wilfordii were prepared and the possibility of entrapment of complex chemicals by liposomes were studied. METHOD: The liposomes containing extracts of T. wilfordii were prepared by thin-film dispersion method, the effect of process parameters and composition of materials on the entrapment efficiency of the main components were studied. The stability of the liposomes dispersion was also evaluated. RESULT: The liposomes made by thin-film dispersion method were mostly small unilamellar vesicles and their particle size was 30 nm to approximately 50 nm. The optimum entrapment efficiency of tripterine and the total alkaloids were respectively 98.10% and 88.63% but the liposomes dispersion was unstable when kept at 4 degrees C. CONCLUSION: The complex chemicals can be entrapped by the liposomes, but its stability need to be improved furtherly.

Extraction of ferulic acid from Angelica sinensis with supercritical CO2.

Extraction of pharmacologically active ingredient of ferulic acid from the root of Angelica sinensis with supercritical CO2 was investigated. The experimental results show that the extract yields were 0.87-4.06% at temperatures from 45 to 65 degrees Celsius and pressures from 30 to 50 MPa, and the maximum content of ferulic aicd in the extracts was about 0.35-0.37%, which is lower than that of 0.61-0.85% by conventional percolation methods. Ethanol was used as co-solvent in different ratios to raw materials in order to increase the content of ferulic acid in the extracts. The experimental results show that both the extract yields and the content of ferulic acid in the extracts increase greatly compared with pure CO2 extraction. When the ratio of ethanol to the raw material was 1.6, the content of ferulic acid in the extracts was 0.91-1.27%, indicating that supercritical fluid extraction (SFE) with CO2 in the presence of suitable co-solvent is superior to percolation in extracting polar ferulic acid from Angelica sinensis.