Exploring the key anti-fatigue components of American ginseng based on metabolomics and zebrafish models / 药学学报

The aim of this paper is to explore the key anti-fatigue active components in the saponin-like composition of American ginseng. The anti-fatigue activity of western ginseng samples was evaluated using a zebrafish model; metabolomics techniques were used to identify the main saponins in western ginseng from different origins; the active substances and relevant targets of the anti-fatigue effect of western ginseng were initially screened by constructing a PPI protein interaction network between western ginseng saponins and disease targets, and the key active ingredients were screened using a molecular docking method; finally, the anti-fatigue activity of the key active ingredients was evaluated using a zebrafish, animal experiment was approved by the Ethics Committee of Shandong Academy of Medical Sciences (SYXK20220005). The anti-fatigue activity of the key active ingredients was evaluated using a zebrafish model. The results of the zebrafish activity evaluation showed that there were significant differences in the activities of the western ginseng samples from the two origins, and a total of 10 different saponins were identified as possibly related to the anti-fatigue activity after further metabolomic testing and pattern discrimination. The core anti-fatigue targets were screened with the help of component-disease target PPI, combined with pharmacophore-like parameters and molecular docking techniques, and pseudoginsenoside F11 was found to have good binding activity to five of the targets. Finally, the zebrafish model revealed that pseudoginsenoside F11 exhibited significant anti-fatigue activity. This study used metabolomics and zebrafish model to screen the key active substances of pseudoginsenoside F11 for its anti-fatigue activity, which will provide a reference for further research on the anti-fatigue of pseudoginsenosides.

[Spatial distribution characteristics of metabolities in rhizome of Paris polyphylla var. yunnanensis: based on MALDI-MSI].

In this study, a method was established for in-situ visualization of metabolite distribution in the rhizome of Paris polyphylla var. yunnanensis. To be specific, through matrix-assisted laser desorption/ionization-mass spectrometry imaging(MALDI-MSI), the spatial locations of steroidal saponins, amino acids, organic acids, phytosterols, phytoecdysones, nucleosides, and esters in rhizome of the medicinal plant were directly analyzed, and six unknown compounds with differential distribution in rhizome tissues were identified. The specific procedure is as follows: preparation of rhizome tissue section, matrix screening and optimization, and MALDI-MSI analysis. The results showed that the steroidal saponins were mainly distributed in the central, amino acids in epidermis and cortex, low-molecular-weight organic acids in central epidermis, phytosterols in the epidermis and lateral cortex, the phytoecdysones in epidermis and cortex, nucleosides(uneven distribution) in epidermis and cortex, growth hormones around the epidermis and cortex, particularly outside the cortex, and esters in cortex with unobvious difference among different tissues. In this study, the spatial distribution of meta-bolites in the rhizome of P. polyphylla var. yunnanensis was characterized for the first time. The result can serve as a reference for identifying and extracting endogenous metabolites of P. polyphylla var. yunnanensis, exploring the synthesis and metabolism mechanisms of the metabolites, and evaluating the quality of medicinal materials.

Dual-Metal N-Heterocyclic Carbene Complex (M = Au and Pd)-Functionalized UiO-67 MOF for Alkyne Hydration-Suzuki Coupling Tandem Reaction.

Metal N-heterocyclic carbene complexes (NHC-M) have been recognized as an important class of organometallic catalysts. Herein, we demonstrate that different NHC-M (M = Au and Pd) species can be simultaneously introduced into a single metal organic framework (MOF) by direct assembly of NHC-M-decorated ligands and metal ions under solvothermal conditions. The obtained UiO-67-Au/Pd-NHBC MOF with different organometallic NHC-M species can be a highly reusable dual catalyst to sequentially promote alkyne hydration-Suzuki coupling reaction. The potential utility of this strategy is highlighted by the preparation of many more new multicatalysts of this type for various organic transformations in a sequential way.

Discovery and identification of quality markers of Sparganii Rhizoma based on zebrafish thrombosis model / 中草药·英文版

Objective: The aim of the present study was to determine the quality marker (Q-Markers) of Sparganii Rhizoma against thrombus through an integration of investigations on its antithrombotic effect, content determination and spectrum-effect correlation analysis. Methods: Based on the concept of Q-Marker, Sparganii Rhizoma was investigated for the identification of chemical component. The pharmacological effects on arachidonic acid-induced thrombosis in zebrafish were also investigated. The material basis in ethanol extract was determined by HPLC-UV. Furthermore, the potential Q-Markers were analyzed and predicted according to the effect-chemical correlation analysis. Finally, the anti-thrombotic Q-Markers were verified through the anti-thrombotic test of monomer components. Results: The model of thrombosis zebrafish was established with larvae exposed to 100 µmol/L arachidonic acid for 1 h. Nine ingredients in Sparganii Rhizoma were identified as 5-hydroxymethylfurfural, vanillic acid, ferulic acid, p-hydroxybenzaldehyde, p-hydroxybenzoic acid, vanillin, protocatechuic acid, p-coumaric acid and isoferulic acid. According to the determination effect of zebrafish thrombosis model and HPLC content analysis results, all the other contents present positive correlation except 5-hydroxymethylfurfural, and the P values of three representative potential Q-Markers (ferulic acid, protocatechuic acid and p-coumaric acid) were 0.002, 0.001 and 0.026, respectively. Conclusion: Sparganii Rhizoma showed a dose-dependent effect on the recovery of reducing cardiac red blood cell on zebrafish model. Three phenolic acids (ferulic acid, protocatechuic acid and p-coumaric acid) were proved to possess the anti-thrombotic effects which could be regarded as the potential Q-Markers for quality assessment of Sparganii Rhizoma.

Electrical and Structural Dual Function of Oxygen Vacancies for Promoting Electrochemical Capacitance in Tungsten Oxide.

Intrinsic defects, including oxygen vacancies, can efficiently modify the electrochemical performance of metal oxides. There is, however, a limited understanding of how vacancies influence charge storage properties. Here, using tungsten oxide as a model system, an extensive study of the effects of structure, electrical properties, and charge storage properties of oxygen vacancies is carried out using both experimental and computational techniques. The results provide direct evidence that oxygen vacancies increase the interlayer spacing in the oxide, which suppress the structural pulverization of the material during electrolyte ion insertion and removal in prolonged stability tests. Specifically, no capacitive decay is detected after 30 000 cycles. The medium states and charge storage mechanism of oxygen-deficient tungsten oxide throughout electrochemical charging/discharging processes is studied. The enhanced rate capability of the oxygen-deficient WO3- x is attributed to improved charge storage kinetics in the bulk material. The WO3- x electrode exhibits the highest capacitance in reported tungsten-oxide based electrodes with comparable mass loadings. The capability to improve electrochemical capacitance performance of redox-active materials is expected to open up new opportunities for ultrafast supercapacitive electrodes.

[Segmental Zoster Paresis:Report of One Case and Literature Review].

Segmental zoster paresis(SZP)is a rare complication in herpes zoster infection,with its symptoms often neglected due to the co-existence of pain.Here we reported a case of SZP.Also,we analyzed 42 Chinese SZP cases in literature,which revealed that the male to female ratio of SZP patients was 13∶8,and the median age of disease onset was 65 years.The most commonly affected region is upper limb.The diagnosis depends mainly on typical medical history and clinical symptoms.Although there is no definite therapy for SZP,the antiviral therapy is the most commonly used treatment,which achieved complete recovery in 78.6% of the patients and partial recovery in 14.3% of the patients.

RP11-81H3.2 Acts as an Oncogene via microRNA-490-3p Inhibition and Consequential Tankyrase 2 Up-Regulation in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a serious threat to human lives and is usually diagnosed at the late stages. Recently, there has been a rapid advancement in the treatment options for HCC, but novel therapeutic targets are still needed, especially for precision medicine. AIMS: We aimed to investigate the involvement of non-coding RNA RP11-81H3.2 in HCC. METHODS: The expression of RP11-81H3.2 was examined in the blood samples of HCC patients, and in the human HCC cell lines, including HepG2, Smmc-7721, and Huh7. Cell proliferation was determined using the CCK-8 and EdU assay, and cell invasion and migration were determined using the transwell/wound healing assay. The effects of RP11-81H3.2 knockdown on in vivo tumor growth were evaluated utilizing the nude mice HepG2 tumor xenograft model. RESULTS: Here, we have identified a long non-coding RNA, RP11-81H3.2, which is enriched in HCC and can promote its proliferation, migration, and invasion both in vitro and in vivo. In addition, our results showed that RP11-81H3.2 binds to and regulate miR-490-3p expression in the HCC cells. Moreover, we found that RP11-81H3.2 regulates the expression of TNKS2 via miR-490-3p. Further, we found that RP11-81H3.2 and miR-490-3p form a regulatory loop; the release of RP11-81H3.2 leads to the suppression of miR-490-3p expression, thus, further enhancing the expression of RP11-81H3.2. CONCLUSIONS: Our data have provided a novel target for the diagnosis and treatment of HCC, and sheds light on the lncRNA-miRNA regulatory nexus that can control the HCC related pathogenesis.

Network pharmacologic molecular mechanism of Shenmai Injection in treatment of COVID-19 combined with coronary heart disease / 中草药

Objective: To analyze the molecular interaction network pathway of Shenmai Injection in the treatment of COVID-19 with coronary heart disease by using network pharmacology. Methods: Using the TCMSP and ETCM to retrieve the chemical constituents of Ginseng Radix et Rhizoma Rubra and Ophiopogonis Radix in Shenmai Injection. The target of the compound was predicted through the SwissTargetPrediction database. The target of COVID-19 with coronary heart disease was screened through the NCBI database and the GeneCards database, and the targets of compound and disease were mapped to obtain the target of the compound for treating the disease. FunRich software and DAVID database were used to perform GO function enrichment analysis and KEGG pathway enrichment analysis, and Excel software and Tableau software to draw bar charts and bubble charts for visualization. Finally, Cytoscape 3.7.1 software was used to build compound-target-pathway network. Glide was used to dock the components of Shenmai Injection with 3CL hydrolase (Mpro). Results: The results showed that ophiopogonin D', ophiopogonin D, ginsenoside Rg2, methyl ophiopogonanone A, ophiogenin-3-O-α-L-rhamnopyranosyl (1→2)-β-D-glucopyranoside, ginsenoside Rb2, ginsenoside R0, ophiopogon A, sanchinoside Rd, ophiopogonanone E, and ginsenoside Re showed higher degrees in the analysis and stronger binding with 3CL hydrolase. Those compounds were the main effective components in the treatment of COVID-19 combined with coronary heart disease, involving 77 targets such as IL6, GAPDH, ALB, TNF, MAPK1, MAPK3, TP53, EGFR, CASP3, and CXCL8. KEGG pathway enrichment analysis revealed that there were 124 (P < 0.05) signaling pathways involving HIF-1 signaling pathway, TNF signaling pathway, sphingolipid signaling pathway, Toll-like receptor signaling pathway, neurotrophin signaling pathway, VEGF signaling pathway, apoptosis, Ras signaling pathway, PI3K-Akt signaling pathway, and prolactin signaling pathway. The results of molecular docking showed that the affinity between the 17 components of Shenmai Injection and the 3CL hydrolase of SARS-CoV-2 was less than -25 kJ/mol. Conclusion: Shenmai Injection can achieve simultaneous intervention of COVID-19 and coronary heart disease by inhibiting cytokine storms, maintaining cardiac function homeostasis, regulating immunity, and antivirals. It presents the network regulation mechanism of mutual influence and complex correlation. This study can provide a scientific basis for the treatment of Shenmai Injection in critically ill patients with COVID-19.

Upregulated expression of serum exosomal miR-375 and miR-1307 enhance the diagnostic power of CA125 for ovarian cancer.

BACKGROUND: Ovarian cancer (OC) is associated with high mortality in gynecological oncology; this is mainly due to the low diagnosis rate. Exosomal miRNA has demonstrated potential as a tumor biomarker. We aimed to explore the diagnostic potential of serum exosomal miR-1307 and miR-375 for OC. METHODS: The first six candidate miRNAs were selected from the previous literature. The relative quantification of qRT-PCR was used to screen for the stability of exosomal miRNAs, followed by validation of the cohort. ROC analysis was employed to analyze the specificity and sensitivity of exosomal miRNA. RESULTS: MiR-1307 and miR-375 were confirmed stably existing in serum exosomes of OC. Moreover, miR-1307 and miR-375 were both significantly up-regulated in serum exosomes of OC compared to ovarian benign and healthy groups. The overexpressed miRNAs showed independent diagnostic power and enhanced the diagnostic accuracy of traditional biomarkers when combined with CA-125 and HE4. MiR-1307 was associated with tumor staging, and miR-375 was associated with lymph node metastasis of OC. CONCLUSION: Our results suggest that serum exosomal miR-1307 and miR-375 could serve as potential tumor biomarkers to improve diagnostic efficiency for OC.

Nickel-metalated porous organic polymer for Suzuki-Miyaura cross-coupling reaction.

A new Ni(ii)-α-diimine-based porous organic polymer, namely Ni(ii)-α-diimine-POP, was constructed in high yield via the Sonogashira coupling reaction between the metallo-building block of Ni(ii)-α-diimine and 1,3,5-triethynylbenzene. Besides the high thermal and chemical stability, the obtained Ni(ii)-α-diimine-POP can be a highly active reusable heterogeneous catalyst to promote the Suzuki-Miyaura coupling reaction. The obtained results indicate that the Ni(ii)-α-diimine-POP herein is a promising sustainable alternative to the Pd-based catalysts for catalysing the C-C formation in a heterogeneous way.

Porous organic polymer with in situ generated palladium nanoparticles as a phase-transfer catalyst for Sonogashira cross-coupling reaction in water.

A new Pd nanoparticle loaded and imidazolium-ionic liquid decorated organic polymer of Pd@PTC-POP was readily fabricated via a Pd(PPh3)4 catalysed in situ one-pot Suzuki cross-coupling reaction between imidazolium attached dibromobenzene and 1,3,5-tri(4-pinacholatoborolanephenyl)benzene. Besides the high thermal and chemical stability, the obtained Pd@PTC-POP can be used as a highly active and reusable phase-transfer solid catalyst to promote the Sonogashira coupling reaction in water. The obtained results indicate that the Pd@PTC-POP herein could create a versatile family of solid phase transfer catalysts for promoting a broad scope of reactions carried out in water.

TCM chemical biology--emerging interdiscipline of "TCM chemistry" and "biology" / 中国中药杂志

Traditional Chinese medicine(TCM) is a research area with highly original innovation features,and is also a Chinese name card to the world. However,TCM owns a unique theoretical system which is quite different from western modern medicine,leading to an awkward situation of deficient modern social identity as well as poor international spread. Therefore,how to establish a research strategy in line with the characteristics of TCM itself to systematically interpret the unique scientific connotation of TCM is always a public hot topic. Based on persistent practical exploration and scientific consideration in TCM,our group firstly promoted the concept of traditional Chinese medicine chemical biology(TCM chemical biology,TCMCB). The major idea of TCMCB is to clarify the nature of TCM regulating life progress to link TCM to modern medicine by using TCM components as chemical tools. Notably,TCMCB mainly focuses on TCM target identification and TCM-guided disease molecular mechanism exploration,further to clarify the basic law of TCM mediating disease process. Finally,TCMCB-guided scientific studies can help explain TCM theory and promote the developmentof modern innovative drugs based on identified targets using TCM active components. Moreover,TCMCB is of vital importance for investigating the scientific nature of biological progress and the pattern of disease occurrence and development,indicating a key significance for modern life science and medicine. This review introduces the definition of TCMCB as well as its academic thought,research method,technology system and scientific significance,for providing new research ideas and scientific thoughts for TCM development.

Study on liver protection and hepatotoxicity of saikosaponin a based on zebrafish model / 中国中药杂志

Bupleuri Radix has both liver protection and hepatotoxicity. Saponins are the main pharmacodynamic and toxic components of Bupleuri Radix. Based on zebrafish physical model and the model of alcoholic fatty liver( AFL) pathology,the liver toxic and protective effect of saikosaponin a( SSa) were assessed. The results indicated that 1. 77 μmol·L-1 SSa showed protective effect to AFL zebrafish. 5. 30 μmol·L-1 SSa was hepatotoxic to healthy zebrafish,but it showed protective effect to AFL zebrafish. 5. 62 μmol·L-1 SSa was hepatotoxic to healthy and AFL zebrafish. This study is benefit for clinical safety of saikosaponin a.

Kinetics and removal formula of methyl mercaptan by ethanol absorption without neglecting solute accumulation.

The wet scrubbing process is commonly adopted for organic odor treatment. In this study, methyl mercaptan (CH3SH) was selected as a representative hydrophobic organic odorant which was treated using an ethanol solution in a scrubbing tower. Results showed that the ethanol solution can retain the ideal CH3SH removal effect for 2.0 h. The following experimental conditions were set: intake load of 4,700 m3 m-2 h-1, spraying load of 5,100 L m-2 h-1, and volume ratio of ethanol/water at 1:5. The solute accumulation of CH3SH in the scrubbing liquid exceeded 3.01 × 10-4 kmol CH3SH/kmol ethanol when the scrubbing tower operated for more than 2.0 h. The mathematical formula which neglected solute accumulation in the ethanol solution exhibited poor adaptability to the removal effect of CH3SH by ethanol absorption. The CH3SH removal effect of solute accumulation in the ethanol solution was explored in long-term operation. Meanwhile, the CH3SH removal rate formula which considered solute accumulation in the ethanol solution could be calculated as η = a'-b'X2/Y1. The kinetic parameters of the formula fitting results were phase equilibrium constant m 0.0076, and overall mass transfer coefficient KY 4.98 kmol m-2 h-1 in the scrubbing tower. These findings can serve as a reference for engineering design and operation for the removal of CH3SH by ethanol absorption.

The protective effect of QZXK in nerve injury using zebrafish model induced by MPTP / 中国药理学通报

Aim To investigate the protective effect of Qi ZhiXiaoke granules ( QZXK ) on nerve injury using zebrafish and nerve cell injury models. Methods The nerve injury model was established using wild zebrafish AB line, 72 hours after fertilization treated with 1-methyl-4-phenyl-1 , 2 , 3 , 6-four pyridine ( MPTP ) .Then QZXK of different doses were administered for three days,and the trajectory of the zebrafish behavior was recorded and analyzed. Neuroblastoma PC12 cells were incubated with different concentrations of QZXK and MPTP,and the cell viability of PC12 cells was de-tected by MTT. The mitochondrial membrane potential and expression of apoptosis related protein Caspase3 were measured by kits. Results Compared with con-trol group,MPTP reduced the movement distance of ze-brafish,and with the increase of concentration, QZXK promoted the movement distance and reversed the swimming behavior abnormality of zebrafish. Compared with control group, QZXK could inhibit the apoptosis induced by MPTP and promote the cell viability of PC12 cells with MPTP. QZXK improved the membranepotential and decreased the expression of Caspase3 . Conclusions QZXK exerts neuroprotective effect in the process of nerve injury induced by MPTP. The mechanism may be related with inhibiting apoptosis of neural cells. These experiment provides experimental and theoretical foundation for QZXK promoting cogni-tive function.

Model establishment of skin damage and molecular mechanism on transgenic zebrafish embryos / 中国药理学通报

Aim To establish a new model of skin damage by u-sing vincristine to transgenic zebrafish (krt4:NTR-hKikGR).Methods Skin fluorescent transgenic zebrafish embryos after 24 h fertilization were treated with the 0.01~0.04 mmol·L-1 vincristine,and zebrafish skin cell ablation was investigated un-der fluorescence microscope after 24 h,at same time skin death cells were detected with TUNEL assay and image processed, then the protein expressions of KRT4, caspase-3 and p53 were assessed with Western blot. Results 0.02 mmol·L-1and 0.04 mmol·L-1vincristine could obviously induce zebrafish skin cell apoptosis(P<0.01) with statistically significant differ-ence compared with the control, and the same result could be accomplished in TUNEL assay. Results of Western bolt showed that vincristine could increase the embryos caspase-3 and p53 expression(P <0.01), while vincristine in high concentration might decrease KRT4 markedly(P<0.01). Conclusion Vin-cristine can induce damage on zebrafish skin with suppression KTR4,which can be used as a new skin damage model.

Tumor-associated autoantibodies are useful biomarkers in immunodiagnosis of α-fetoprotein-negative hepatocellular carcinoma.

AIM: To determine the prevalence and diagnostic value of autoantibodies in α-fetoprotein (AFP)-negative hepatocellular carcinoma (HCC). METHODS: Fifty-six serum samples from AFP-negative HCC cases, 86 from AFP-positive HCC cases, 168 from chronic liver disease cases, and 59 from normal human controls were included in this study. Autoantibodies to nucleophosmin (NPM)1, 14-3-3zeta and mouse double minute 2 homolog (MDM2) proteins in AFP-negative HCC serum were evaluated by enzyme-linked immunosorbent assay. Partially positive sera were further evaluated by western blotting. Immunohistochemistry was used to detect the expression of three tumor-associated antigens (TAAs) in AFP-negative HCC and normal control tissues. RESULTS: The frequency of autoantibodies to the three TAAs in AFP-negative HCC sera was 21.4%, 19.6% and 19.6%, which was significantly higher than in the chronic liver disease cases and normal human controls (P < 0.01) as well as AFP-positive HCC cases. The sensitivity of the three autoantibodies for diagnosis of AFP-negative HCC ranged from 19.6% to 21.4%, and the specificity was approximately 95%. When the three autoantibodies were combined, the sensitivity reached 30.4% and the specificity reached 91.6%. CONCLUSION: Autoantibodies to NPM1, 14-3-3zeta and MDM2 may be useful biomarkers for immunodiagnosis of AFP-negative HCC.

Decreased Expression of Hsa_circ_00001649 in Gastric Cancer and Its Clinical Significance.

Background. It has been reported that circRNAs are differentially expressed in a wide range of cancers and could be used as a new biomarker for diagnosis. However, the correlation between circRNAs and gastric cancer (GC) it is still unclear. Materials and Methods. In this study, by using real-time quantitative reverse transcription-polymerase chain reactions (qRT-PCRs), we detected the expression level of hsa_circ_0001649 in tissue and serum samples from GC patients. Results. We found that hsa_circ_0001649 expression was significantly downregulated in GC tissue compared with their paired paracancerous histological normal tissues (PCHNTs) (P < 0.01). We next analyzed the expression level of hsa_circ_0001649 in serum samples between preoperative and postoperative GC patients. We found that its level in serum was significantly upregulated after surgery (P < 0.01). The area under the receiver operating characteristic (ROC) curve was 0.834. Moreover, the expression level of hsa_circ_0001649 was significantly correlated with pathological differentiation (P = 0.039). Conclusion. Our test suggested that hsa_circ_0001649 was significantly downregulated in GC and may become a novel potential biomarker in the diagnosis of GC.

Biosafety hazard of laboratory animals in medical colleges and its prevention and control / 中国比较医学杂志

Biosafety hazard has been paid high attention with increasing use of animal species and quantities in medical colleges. In the present paper, we analyze potential biosafety risks in medical colleges from characteristics of biosafety environment, experiment activity, zoonosis, laboratory animal management, etc. , then give some advices on prevention and control of biosafety hazards.

Biosafety hazard of laboratory animals in medical colleges and its prevention and control / 中国比较医学杂志

Biosafety hazard has been paid high attention with increasing use of animal species and quantities in medical colleges. In the present paper, we analyze potential biosafety risks in medical colleges from characteristics of biosafety environment, experiment activity, zoonosis, laboratory animal management, etc. , then give some advices on prevention and control of biosafety hazards.