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Active substances in traditional Chinese Medicine (TCM) contain not only a variety of small molecules, but also many other macromolecules (TCMMs), such as proteins, peptides and polysaccharides. Active TCMM can achieve good therapeutic effects by regulating the body's overall function with lower side effects. This review summarized the literatures published in recent years on the application of fluorescently labeled tracer technique for detection of natural active macromolecules in TCM. Classified by fluorescent markers, applications of fluorescein, rhodamine, and quantum dots (QDs) in TCMM active tracer are reviewed, and the methods and principles of TCMM fluorescent marker are illustrated. Studies on active TCMMs and their action mechanism are quite difficult due to a multitarget, multicomponent, and multipath system of TCM. However, the development of fluorescently labeled active tracer technique (FLATT) provides this research with new tools. Traditional fluorescent markers have many deficiencies, such as easily quenched, short luminous cycle, and intrinsic toxicity. Relatively, FLATT has many obvious advantages, and its application in TCMM is still at the early stage. In order to improve the overall level of fluorescence labeling in TCMM active tracer, the improvement on FLATT's detection sensitivity and biological affinity is urgent and critical to allow study of these interesting molecules. [ABSTRACT FROM AUTHOR]

This study aims to investigate the incidence of hepatitis B virus (HBV) reactivation in inflammatory arthritis (IA) patients with HBV infection using anti-tumor necrosis factor (TNF) agents and evaluate the efficacy of antiviral therapy in reducing the risk of viral reactivation in chronic HBV infection. IA patients using anti-TNF agents from six centers were enrolled. Their HBV infection conditions and ALT and HBV-DNA levels were monitored periodically. Among the six chronic hepatitis B patients, HBV reactivation was found in two patients without antivirus prophylaxis and no viral replication was detected in the other four patients with antivirus prophylaxis. In the 31 inactive carriers, the increase of viral load was detected in 6 of 22 (27.3 %) patients without antiviral prophylaxis, and there was no viral reactivation in the other 9 patients with antiviral prophylaxis. HBV reactivation was not found in the 50 patients with resolved HBV infection. It is suggested that anti-TNF therapy might increase the risk of HBV reactivation in patients with chronic HBV infection, and antiviral prophylaxis could effectively decrease the risk. Anti-TNF agents seem to be safe in patients with resolved HBV infection. [ABSTRACT FROM AUTHOR]

Highlights: [•] Combining epitope prediction methods with molecular docking techniques to identify MHC class I restricted T-cell epitopes. [•] Based on available experimental data, the prediction accuracy is up to 90%. [•] Providing a valuable step forward for the design of better vaccines. [•] Better understanding the activation of T-cell epitopes by MHC binding peptides. [Copyright &y& Elsevier]

Abstract: Based on molecular modeling techniques we constructed a rational 3D model of ORF3 in SARS coronavirus (SARS-CoV). Our studies suggest that the function of ORF3 could be involved in FAD/NAD binding according to its predicted structure and comparison with other structure neighbors. Furthermore, we identified three pairs of non-canonical N–H⋯π interactions in the structure of ORF3, which can make contributions to the stability of protein structure. These results provide important clues for better understanding of SARS-CoV ORF3 and trying new therapeutic strategies. [Copyright &y& Elsevier]

Abstract: Pharmacophore-based virtual screening is an effective, inexpensive and fast approach to discovering useful starting points for drug discovery. In this study, we developed a pharmacophore model for the main proteinase of severe acute respiratory syndrome coronavirus (SARS-CoV). Then we used this pharmacophore model to search NCI 3D database including 250, 251 compounds and identified 30 existing drugs containing the pharmacophore query. Among them are six compounds that already exhibited anti-SARS-CoV activity experimentally. This means that our pharmacophore model can lead to the discovery of potent anti-SARS-CoV inhibitors or promising lead compounds for further SARS-CoV main proteinase inhibitor development. [Copyright &y& Elsevier]

The spike protein of SARS-associated coronavirus (SARS-CoV) is an important target for anti-SARS drug discovery. Its S1 domain is responsible for receptor binding and SARS-CoV entry into cells. In this study, we constructed a rational 3D model for S1 domain of SARS-CoV spike protein by fold recognition and molecular modeling techniques. We found that there is a structure similarity between S1 protein and influenza virus neuraminidase. Our analyses suggest that the existing anti-influenza virus inhibitors and anti-neuraminidase antibody could be used as a starting point for designing anti-SARS drugs, vaccines and antibodies. Interestingly, our prediction for antibody is consistent with a recently experimental discovery of anti-SARS antibody. [Copyright &y& Elsevier]

The SARS-associated coronavirus (SARS-CoV) main proteinase is a key enzyme in viral polyprotein processing. To allow structure-based design of drugs directed at SARS-CoV main proteinase, we predicted its binding pockets and affinities with existing HIV, psychotic and parasite drugs (lopinavir, ritonavir, niclosamide and promazine), which show signs of inhibiting the replication of SARS-CoV. Our results suggest that these drugs and another two HIV inhibitors (PNU and UC2) could be used as templates for designing SARS-CoV proteinase inhibitors. [Copyright &y& Elsevier]

The main proteinase of SARS-associated coronavirus (SARS-CoV) plays an important role in viral transcription and replication, and is an attractive target for anti-SARS drug development. The important thing is to understand its binding mechanism with possible ligands. In this study, we investigated possible noncanonical interactions, potential inhibitors, and binding pockets in the main proteinase of SARS-CoV based on its recently determined crystal structure. These findings provide a wide clue to searching for anti-SARS drug. Interestingly, we found that similar structure patterns exist in SARS-CoV main proteinase with Poliovirus 3c Proteinase, Rhinovirus 3c Protease, Nsp4 Proteinase From Equine Arteritis Virus, Hepatitis C Virus Ns3 Protease, Hepatitis A Virus 3c Protease, and Dengue Virus Ns3 Protease. It suggests that the available drugs in these viruses could be used to fight SARS disease. [Copyright &y& Elsevier]

Abstract: Aim: This study investigated the common initial clinical presentations of primary Sjögren's syndrome (pSS) with interstitial lung disease (ILD) and explored differences between sicca and non‐sicca onset pSS‐ILD patients. Method: A total of 1341 SS patients hospitalized between 2003 and 2012 were retrospectively reviewed. Of them, 102 were analyzed and recruited to examine the differences between non‐sicca and sicca onset. Results: Fifty‐one percent of pSS‐ILD patients presented with non‐sicca onset. Although the mean diagnosis time was equal, only 4% of non‐sicca onset patients were diagnosed with pSS at onset versus 34% with sicca onset (P = 0.000). Hyperglobulinemia, elevated rheumatoid factor (RF) titer, and anti‐SSA and/or anti‐SSB presence were less predominant in patients with non‐sicca onset (immunoglobulin G, 16 [12–21] vs. 21 [15–28] g/L, P = 0.032; RF, 22 [20–171] vs. 104 [20–237] IU/mL, P = 0.048; anti‐SSA and/or anti‐SSB presence, 33% vs. 72%, P = 0.000). The usual interstitial pneumonia pattern was more commonly seen in non‐sicca onset patients (20.0% vs. 14.3%). The high‐resolution computed tomography score was higher (12 [88–15] vs. 8 [5–13], P = 0.070) and predicted total lung capacity and forced vital capacity were lower (87 ± 23% vs. 97 ± 20%, P = 0.050; 88 ± 28% vs. 100 ± 27%, P = 0.089) in non‐sicca patients. Conclusion: Non‐sicca is a common initial manifestation in pSS‐ILD. Anti‐SSA presence, elevated RF titer and hyperglobulinemia were less predominant, and pulmonary complications were more progressive and severe in non‐sicca onset patients than sicca onset patients. [ABSTRACT FROM AUTHOR]

18 β -glycyrrhetinic acid (GA) is the active ingredient of the traditional Chinese medicinal herb Glycyrrhizae radix et rhizoma. We previously demonstrated that GA inhibited tumor growth in hepatocellular carcinoma (HCC). However, the effect of GA on transforming growth factor- β (TGF- β) -induced epithelial-mesenchymal transition (EMT) and metastasis were still unclear. In this study, in vitro transwell assays and immunofluorescence (IF) demonstrated that GA inhibited TGF- β -induced migration, invasion and EMT of HCC cells. However, it had little effect on the inhibition of proliferation by TGF- β. Moreover, we confirmed that GA suppressed the metastasis of HCC cells in vivousing an ectopic lung metastasis model. Furthermore, we found that GA inhibited TGF- β -induced EMT mainly by reducing the phosphorylation of signal transducer and activator of transcription 3 (STAT3), which played an essential role in TGF- β -induced EMT and cell mobility. Mechanistically, GA inhibited the phosphorylation of STAT3 by increasing the expression of Src homology 2 domain-containing protein tyrosine phosphatases 1 and 2 (SHP1 and SHP2). Therefore, we concluded that GA inhibited TGF- β -induced EMT and metastasis via the SHP1&SHP2/STAT3/Snail pathway. Our data provide an attractive therapeutic target for future multimodal management of HCC. [ABSTRACT FROM AUTHOR]

Background: Aberrant TAK1 (transforming growth factor β‐activated kinase 1) activity is known to be involved in a variety of malignancies, but the regulatory mechanisms of TAK1 remain poorly understood. GRAMD4 (glucosyltransferase Rab‐like GTPase activator and myotubularin domain containing 4) is a newly discovered p53‐independent proapoptotic protein with an unclear role in HCC (hepatocellular carcinoma). Results: In this research, we found that GRAMD4 expression was lower in HCC samples, and its downregulation predicted worse prognosis for patients after surgical resection. Functionally, GRAMD4 inhibited HCC migration, invasion and metastasis. Mechanistically, GRAMD4 interacted with TAK1 to promote its protein degradation, thus, resulting in the inactivation of MAPK (Mitogen‐activated protein kinase) and NF‐κB pathways. Furthermore, GRAMD4 was proved to recruit ITCH (itchy E3 ubiquitin protein ligase) to promote the ubiquitination of TAK1. Moreover, high expression of TAK1 was correlated with low expression of GRAMD4 in HCC patients. Conclusions: GRAMD4 inhibits the migration and metastasis of HCC, mainly by recruiting ITCH to promote the degradation of TAK1, which leads to the inactivation of MAPK and NF‐κB signalling pathways. [ABSTRACT FROM AUTHOR]

BACKGROUND Spirulina platensis is recognized as one of the most nutritious foods, containing a high protein content of up to 70%. Meanwhile, he interest in using natural protein resources to develop bioactive peptides is steadily increasing. Therefore, this study released the bioactive peptides from S. platensis by enzymatic hydrolysis using pepsin (1:3000 U g−1), and their amino acid sequences were determined by de novo sequencing. On this basis, the antioxidant activities of synthesized bioactive peptides were comprehensively evaluated by 2,2′‐azinobis‐3‐ethylbenzothiazolin‐6‐sulfonic acid assay, 1,1‐diphenyl‐2‐picryhydrazyl assay, and cell hemolysis assay induced by 2,2′‐azobis‐(2‐amidino‐propane) dihydrochloride (AAPH). RESULTS: The degree of hydrolysis and recovery percentage of pepsin hydrolysis were 172 and 825 g kg–1 respectively, and FFEFF (P1: m/z 736.4, 8%), EYFDALA (P2: m/z 828.4, relative intensity 18.5%), and VTAPAASVAL (P3: m/z 899.5, relative intensity 17.3%) were purified and identified. P2 possessed an excellent radical scavenging activity compared with P1, P3, and vitamin C, which was contributed to by its high β‐sheet conformation and specific amino acid compositions. Moreover, P2 significantly attenuated AAPH‐induced oxidative hemolysis of erythrocytes and protected the erythrocytes, because it reduced the formation of malondialdehyde and increased the enzyme activities of superoxide dismutase, catalase, and glutathione peroxidase in erythrocytes. CONCLUSION: This study provided insights into the potential antioxidant function of the synthesized peptides originated from the bioactive peptides of S. platensis proteins, which would contribute to the development of natural antioxidant from new protein resources. © 2020 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

To determine the expression of Semaphorin3A (Sema3A) in rheumatoid arthritis (RA) patients, and analyze the correlation between serum Sema3A and the pathogenesis of RA. The concentration of serum Sema3A and its mRNA expression level were detected in RA patients. The association of serum Sema3A level with clinical and laboratory features of RA were analyzed. Serum Sema3A of 130 RA patients (15.89 ± 8.58 ng/ml) was significantly higher than that of 150 HC (6.96 ± 2.62 ng/ml) and 215 patients with other rheumatic diseases (P < 0.05). Consistent with the serum level, the Sema3A mRNA level was also higher in RA patients’ PBMC than that in HC (1.8-fold increase, P < 0.01). The serum level of Sema3A was correlated with platelet counts (r = 0.229), ESR (r = 0.172), RF (r = 0.230), IgM (r = 0.254) and Sharp score (r = 0.254), and bone mineral density (BMD) of lumbar spine (r = 0.263). Serum Sema3A was also fundamentally higher in AKA-, APF-, anti-CCP-positive groups compared with negative groups (P < 0.05). The ROC curve showed that the optimum diagnostic cutoff value for Sema3A was 10.881 ng/ml. RF level and antibodies (anti-CCP, APF, AKA, and GPI) positive rates were significantly higher in Sema3A positive group. Sharp score was also higher, although without significance. The expression of Sema3A is significantly elevated in RA patients. The level of serum Sema3A is positively correlated with inflammatory factors (including ESR, IgM, and RF) and is associated with auto-antibody production and bone destruction. [ABSTRACT FROM AUTHOR]

Abstract: Aim: This study was conducted to examine the clinical characteristics of new‐onset systemic lupus erythematosus (SLE) during pregnancy. Methods: We performed a retrospective study of all pregnancies in patients with SLE managed at The People's Hospital of Peking University from 2008 to 2015. In total, 97 pregnancies were identified and studied, 22 of which were first diagnosed with SLE during pregnancy or puerperium. Results: New‐onset SLE mainly occurred during the first and second pregnancy trimesters. Blood and multi‐organ involvement were detected in 95.45% and 45.45% of new‐onset patients, respectively, and both had a higher incidence than in active patients. Thrombocytopenia was the most common blood involvement in new‐onset patients. All three maternal deaths occurred in new‐onset patients. There were nine (40.91%) fetal losses, three (13.64%) low birth weight infants, one (4.54%) fetal malformation and two (9.09%) cases of neonatal lupus in new‐onset patients. Conclusion: New‐onset pregnant SLE patients were characterized with blood system involvement and generally experienced more adverse maternal outcomes than active patients with SLE history. However, adverse fetal outcomes in new‐onset patients were the same as those of active patients with an SLE history. [ABSTRACT FROM AUTHOR]

A comparison of extraction processes, volatile compounds analysis and antioxidant activities of essential oils (EOs) from Cirsium japonicum Fisch. ex DC and Cirsium setosum (Willd.) M.Bieb., two morphological and aroma similar species, were investigated. In total, 143 different constituents were assigned, which were further grouped into hydrocarbons, alcohols, esters, ketones, carboxylic acids, aldehydes, aromatics. Results of HS-SPME revealed that the similar grassy and fruity aromas of C. japonicum and C. setosum derived from Hexyl alcohol, 1-Pentanol, 6,10,14-trimethyl-2-Pentadecanone, etc. In addition, HD was employed to gather EOs. Compared with the Standard Method, yields of EOs by the Optimum Method from C. japonicum and C. setosum increased by 86.58 ± 4.28% and 102.60 ± 1.57%, respectively. Chemical analysis by GC–MS revealed that the high temperature of the optimal condition decreased the types of EOs compounds or changed some compounds into other hot-steady compounds. Furthermore, antioxidant activity analysis (DPPH, ABTS, and FRAP assays) indicated that EOs extracting by the optimized condition of both C. japonicum and C. setosum possessed much higher FRAP value and potent ABTS radical scavenging ability. Therefore, the study could pave the way for the extraction of EOs and further developing of C. japonicum and C. setosum resources. [ABSTRACT FROM AUTHOR]

In this study, mixed hemimicelles solid-phase extraction (MHSPE) based on sodium dodecyl sulfate (SDS) coated nano-magnets Fe 3 O 4 was investigated as a novel method for the extraction and separation of four banned cationic dyes, Auramine O, Rhodamine B, Basic orange 21 and Basic orange 22, in condiments prior to HPLC detection. The main factors affecting the extraction of analysts, such as pH, surfactant and adsorbent concentrations and zeta potential were studied and optimized. Under optimized conditions, the proposed method was successful applied for the analysis of banned cationic dyes in food samples such as chili sauce, soybean paste and tomato sauce. Validation data showed the good recoveries in the range of 70.1–104.5%, with relative standard deviations less than 15%. The method limits of determination/quantification were in the range of 0.2–0.9 and 0.7–3 μg kg −1 , respectively. The selective adsorption and enrichment of cationic dyes were achieved by the synergistic effects of hydrophobic interactions and electrostatic attraction between mixed hemimicelles and the cationic dyes, which also resulted in the removal of natural pigments interferences from sample extracts. When applied to real samples, RB was detected in several positive samples (chili powders) within the range from 0.042 to 0.177 mg kg −1 . These results indicate that magnetic MHSPE is an efficient and selective sample preparation technique for the extraction of banned cationic dyes in a complex matrix. [ABSTRACT FROM AUTHOR]

Herein, a series of 3-phenyliminoindolin-2-one derivatives were designed, synthesized, and screened for their antidepressant and anticonvulsant activities. The IR spectra of the compounds afforded NH stretching (3340-3346 cm−1) bands and C=O stretching (1731-1746 cm−1). In the 1H- NMR spectra of the compounds, N-H protons of indoline ring were observed at 10.65-10.89 ppm generally as broad bands, and 13C- NMR spectra of the compounds C=O were seen at 161.72-169.27 ppm. Interestingly, compounds 3o, 3p and 3r significantly shortened immobility time in the The forced swimming test (FST) and The tail suspension test (TST) at 50 mg/kg dose levels. In addition, compound 3r exhibited higher levels of efficacy than the reference standard fluoxetine but had no effect on locomotor activity in the open-field test. Compound 3r significantly increased serotonin and norepinephrine and the metabolite 5-hydroxyindoleacetic acid in mouse brain, suggesting that the effects of compound 3r may be mediated through these neurotransmitters. In the seizure screen, 15 compounds showed some degree against PTZ-induced seizure at a dose of 100 mg/kg, and the tested compounds did not show any neurotoxicity at a dose of 300 mg/kg in the rotarod test. [ABSTRACT FROM AUTHOR]

In this study, an efficient, fast and sensitive method for the simultaneous determination of eleven synthetic color additives (Allura red, Amaranth, Azo rubine, Brilliant blue, Erythrosine, Indigotine, Ponceau 4R, New red, Sunset yellow, Quinoline yellow and Tartrazine) in flour and meat foodstuffs is developed and validated using HPLC coupled with DAD and MS/MS. The color additives were extracted with ammonia–methanol and was further purified with SPE procedure using Strata-AW column in order to reduce matrix interference. This HPLC–DAD method is intended for a comprehensive survey of color additives in foods. HPLC–MS/MS method was used as the further confirmation and identification. Validation data showed the good recoveries in the range of 75.2–113.8%, with relative standard deviations less than 15%. These methods are suitable for the routine monitoring analysis of eleven synthetic color additives due to its sensitivity, reasonable time and cost. [ABSTRACT FROM AUTHOR]

In order to promote the construction of the experiment teachers in colleges and universities, the exploration and practice were carried out from four aspects - personnel recruitment, orientation training, cultural construction and process management. The paper summed up the flowchart of the meticulous management of the experiment teachers in cofleges and universities in practice, it mainly includes four links as the meticulous recruitment of the experiment teachers in cofleges and universities, the meticulous inductive education of the experiment teachers in cofleges and universities, the meticulous construction of laboratory culture in cofleges and universities and the meticulous management of the experiment teachers in cofleges and universities. Furthermore, the responsibilities of the university, the coflege and the experiment center involved in each link of the flowchart were carried out perfection. And the authors developed the nine rings recruitment method for experiment teachers, the ten rings orientation training system for new experiment teachers, the four rings laboratory culture construction system and the five rings meticulous management system for the experiment teachers. The results of practice showed that the implementation of meticulous management in accordance with the flowchart of the meticulous management of the experiment teachers in cofleges and universities can effectively improve the level of the experiment teachers and increase working efficiency. [ABSTRACT FROM AUTHOR]

Objective. To investigate the prevalence of eight common rheumatic diseases in a large Chinese population.Methods. A population-based epidemiological investigation of the prevalence of eight common rheumatic diseases in a suburb of Beijing was conducted in 14 642 individuals. A community-based survey was carried out using a screening questionnaire. Positive responders were included in a clinical and laboratory examination. Diagnosis was based on the criteria of ACR or those used widely in literature.Results. A total of 10 556 inhabitants were interviewed. Forty-three cases of RA were identified with an age-adjusted prevalence of 0.28% (95% CI 0.19%, 0.41%). Gout was diagnosed with a crude prevalence of 0.09% (95% CI 0.05%, 0.17%). Psoriasis was reported in 28 individuals with a prevalence of 0.27% (95% CI 0.18%, 0.38%). This included two cases diagnosed with PsA, resulting in a prevalence of 7.14% (95% CI 0.88%, 23.5%) in psoriasis patients and 0.02% (95% CI 0%, 0.07%) in the general population. Three individuals were identified with SLE, with a prevalence of 0.03% (95% CI 0%, 0.06%). One individual was identified with SSc and the calculated prevalence was 0.01% (95% CI 0%, 0.05%). One case of Behçet's disease was identified, giving a prevalence of 0.01% (95% CI 0%, 0.05%).Conclusion. This large-scale epidemiological survey provides an estimate of the burden of rheumatic diseases in China. [ABSTRACT FROM PUBLISHER]

Abstract: Gamma-tocotrienol has demonstrated anti-proliferative effect on breast cancer (BCa) cells, but mechanisms involved are largely unknown. This study aimed at deciphering the molecular pathways responsible for its activity. Our results showed that treatment of BCa cells with gamma-tocotrienol resulted in induction of apoptosis as evidenced by activation of pro-caspases, accumulation of sub-G1 cells and DNA fragmentations. Examination of the pro-survival genes revealed that the gamma-tocotrienol-induced cell death was associated with suppression of Id1 and NF-κB through modulation of their upstream regulators (Src, Smad1/5/8, Fak and LOX). Meanwhile, gamma-tocotrienol treatment also resulted in the induction of JNK signaling pathway and inhibition of JNK activity by specific inhibitor partially blocked the effect of gamma-tocotrienol. Furthermore, synergistic effect was observed when cells were co-treated with gamma-tocotrienol and Docetaxel. Interestingly, in cells that treated with gamma-tocotrienol, alpha-tocopherol or β-aminoproprionitrile were found to partially restore Id1 expression. Meanwhile, this restoration of Id1 was found to protect the cells from gamma-tocotrienol induced apoptosis. Consistent outcome was observed in cells ectopically transfected with the Id-1 gene. Our results suggested that the anti-proliferative and chemosensitization effect of gamma-tocotrienol on BCa cells may be mediated through downregulation of Id1 protein. [Copyright &y& Elsevier]