AIM: To evaluate the changes of microRNA (miRNA) in hepatocytes during hydrogen peroxide-induced oxidative stress injury, and to observe the alleviating effect of mesenchymal stem cell-conditioned medium (MSC-CM) in this progress.METHODS: The hepatocyte oxidative stress injury model was established using hydrogen peroxide and human normal liver cell line L02.MSC-CM was prepared using centrifugation and filter.The effects of MSC-CM on hepatocyte injury were evaluated by apoptosis analysis, cell viability detection, cell cycle, and mitochondrial membrane po-tential (MMP).Twenty-one differentially expressed miRNAs were selected by gene chip hybridization, in which miR-143, miR-145, miR-301a and let-7a were confirmed by RT-qPCR.Bioinformatics software was utilized to predict target proteins of these miRNAs, and then the proteins were verified by Western blot.RESULTS: MSC-CM markedly attenuated hydrogen peroxide-induced oxidative stress injury by reducing apoptosis, promoting cell viability and regulating cell cycle.The ex-pression of miR-143, miR-145, miR-301a and let-7a, indentified by RT-qPCR, increased under the condition of oxidative stress injury, while decreased after MSC-CM treatment.The expression of miR-143 predicted target proteins, HK2 and ADRB1, decreased under the hydrogen peroxide-exposure, while increased after MSC-CM treatment, which is consistent with the regulatory trend of miR-143.CONCLUSION: MSC-CM might attenuate hydrogen peroxide induced oxidative stress injury via inhibiting apoptosis and regulating some miRNA expression.

The technique of liquisolid compress is a new technique developed in 1990s, which was considered to be the most promising technique to improve the dissolution of water-insoluble drugs. In this article, tanshinone II(A) and the extracts of the ester-solubility fractions were chosen as the model drugs to evaluate the effects of the liquisolid technique for enhancement of dissolution properties of tanshinone II(A). Several liquisolid tablets (LS) formulations containing different dosage of drugs and various liquid vehicle were pre-pared and for all the formulations, microcrystalline cellulose and silica were chosen as the carrier and coating materials to evaluate their flow properties, such as angle of repose, Carr's compressibility index and Hausner's ratio. The interaction between drug and excipients in prepared LS compacts were studied by differential scanning calorimetry(DSC) and X-ray powder diffraction (XRPD). The dissolution curves of tanshinone II(A) from liquisolid compacts were investigated to determine the technique's effect in improving the dissolution of tanshinone II(A) and its impacting factors. According to the results, the dissolution increased with the rise in the dissolution of the liquid-phase solvent. The R-value and drug dosage can significantly affect the drug release, but with less impact on active fractions. This indicated that liquisolid technique is a promising alternative for improvement of dissolution property of water-soluble drugs, and can make a synergistic effect with other ester-soluble constituents and bettern improve the release of tanshinone II(A). Therefore, the technique of liquisolid compress will have a better development prospect in traditional Chinese medicines.
Calorimetry, Differential Scanning ; Diterpenes, Abietane ; chemistry ; Solubility ; X-Ray Diffraction

Child ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell

"Omics" and bioinformatics have brought new ideas to the study of traditional Chinese medicine. This study used metabonomics and network pharmacology to investigate the pharmacodynamic basis and regulation of Qishen Yiqi dropping pill (QDP) improving cardiac energy metabolism in rats with heart failure (HF). ¹H NMR metabonomics analysis showed that eight metabolites, including carnitine, glutamine, creatine, proline, homocitrulline, lactic acid, taurine and alanine appeared significant callback after QDP treatment for HF. The results indicate that QDP regulates the metabolism of carbohydrate, lipid, ATP and protein. The animal experiment was conducted in accordance with the regulations of the Ethics Committee for Experimental Animal Management and Animal Welfare of Institute of Materia Medica, Chinese Academy of Medical Sciences. A "drug-component-target-disease" network was established using network pharmacology, and the "component-target" sub-network related to the above energy metabolism processes was extracted by combining metabonomics results. Results revealed 79 chemical compounds and 47 potential targets of QDP involved in the regulation of energy metabolism, and identified key chemical components including ursolic acid, notoginsenoside G, ginsenoside-Rh1, and core targets such as INS, PPARG, and AKT1. The results also demonstrated the complex multi-target and multi-component relationship between QDP and HF from the perspective of energy metabolism. The molecular docking technique verified a strong interaction between some targets and chemical compounds, with affinities less than -5 kcal·mol^-1. The results of this study provide useful information for the clinical application, development, and utilization of QDP.

Studies have shown that a variety of diseases such as cardiovascular disease, renal disease and cancer are closely related to trimethylamine oxide (TMAO). Clinically, abnormal elevation of TMAO has been used as an evaluation index of atherosclerosis (AS) prior to imaging. In this study, we investigated the effects of lipid metabolism disorders as well as pharmacological interventions on urinary TMAO using a hyperlipidemic golden gopher model. The study used 48 Syrian golden hamster modeled with a high-fat diet for 2 weeks, and then ezetimibe, simvastatin, ezetimibe and simvastatin groups were administered for 4 consecutive weeks, as well as the clinical trial drug, IMM-H007, for pharmacological intervention. The animal experiment was conducted in accordance with the regulations of the Ethics Committee for Experimental Animal Management and Animal Welfare of Institute of Materia Medica, Chinese Academy of Medical Sciences (approval number: SCXK (Beijing) 2021-0011). Urine from rats was analyzed for 2D band selective heteronuclear single quantum coherence (2D bs-HSQC) at week 2 and 4 after drug administration. The results indicated that, in comparison to the control group, the high-fat diet significantly elevated urinary TMAO levels in the model group of hamsters after both 2 and 4 weeks of treatment (P < 0.05). Urinary TMAO levels were significantly reduced (P < 0.05) in the model group after 2 or 4 weeks of intervention with ezetimibe, simvastatin, combination therapy, and IMM-H007, showing a marked decrease even after 2 weeks of treatment. The detection of TMAO could precede the measurement of serum biochemical indicators, facilitating earlier efficacy assessment. This study evaluated the modulatory effects of clinical drugs and clinical trial drugs on TMAO, which provides useful information for clinical drug use and drug research. It also provides a means of TMAO detection based on 2D NMR technology, which is helpful for the clinical application of TMAO detection index.

OBJECTIVETo study the effects of cardiovascular function in dental extraction on hypertensive patients by inhalation 50% nitrous oxide.

METHODSThe 30 hypertensive patients were randomly allocated into two groups: A group inhalation the 50% nitrous oxide and oxygen, B group inhalation the air and O(2). To measured the HR, BP, and SpO(2) in dental extraction.

RESULTSIn a group the changes of blood pressure and heart rate are more smoother than B group. Two groups were significant in HR, BP and SpO(2) (P < 0.01).

CONCLUSIONSInhalation with 50% nitrous oxide can keep the stability of cardiovascular system and it is a valid method in dental extraction on hypertensive patients.

Administration, Inhalation ; Aged ; Anesthetics, Inhalation ; administration & dosage ; pharmacology ; Blood Pressure ; drug effects ; Female ; Heart Rate ; drug effects ; Hemodynamics ; drug effects ; Humans ; Hypertension ; physiopathology ; Male ; Middle Aged ; Nitrous Oxide ; administration & dosage ; pharmacology ; Oxygen ; blood ; Partial Pressure ; Time Factors ; Tooth Extraction

Objective:To explore the anti-tumor effect of Tanshinone Ⅱ A microemulsion and to research its reversal effect of multidrug resistance on SMMC-7721/VCR tumor.Methods The human hepatocellular carcinoma cell line SMMC-7721 and human hepatocellar carcinoma drug-resisitant cell line SMMC-7721/VCR were cultured in vitro.Each cell was divided three groups:experimental group (cell suspension + 3 kinds of anti-tumor drugs),negative control group (cell suspension + culture) and blank control group (culture).Tanshinone Ⅱ A microemulsion and Tanshinone Ⅱ A in five concentrations (0.5,1.0,2.0,4.0,8.0 μg · mL-1) intervention SMMC-7721 cells.The inhibition effect of Tanshinone Ⅱ A microemulsion of 0.5,1,2,4,8 μg · mL-1 in 24 h and 48 h on SMMC-7721 cell proliferation was tested by MTT assay.The IC50 of VCR,CDDP,5-fluorouracil(5-Fu) for the cell of SMMC-7721,SMMC-7721/VCR were determined by MTT assay.The IC50 of VCR,CDDP,5-Fu for the SMMC-7721/VCR after intervention with Tanshinone Ⅱ A microemulsion were determined also by MTT assay.The sensitivity change and drug reversal effect of Tanshinone Ⅱ A microemulsion before and after intervention on the SMMC-7721/VCR cell line was investigated by MTT assay.Results The inhibition rate after intervention with Tanshinone Ⅱ A microemulsion on SMMC-7721 cells for 48 h were 47.93％,55.92％,66.34％,95.61％.Accordingly,the inhibition rate of Tanshinone Ⅱ A were 38.83％,49.31％,58.24％,82.46％.The half inhibitory concentration were (0.67 ±0.32),(1.91 ±0.53) μg · mL-1,respectively.The difference had statistical significance (all P ＜ 0.01).With the increase of concentration,the inhibition rate increased of Tanshinone Ⅱ A microemulsion on SMMC-7721 cell with dose dependence and time dependence.When the concentration of Tanshinone ⅡA and its microemulsion for 0.5 ug · mL-1,on SMMC-7721 cells and SMMC-7721/VCR cell growth inhibition rate were 9.53％,7.74％,both less than 10％ and no obvious toxic effect,so concentration of 0.5 μg · mL-1 was choosed as liver cancer drug resistant safety experiment dose.When 0.5 ug · mL-1 Tanshinone Ⅱ A microemulsion was intervention on SMMC-7721/VCR cell,VCR to SMMC-7721/VCR half inhibitory concentration was from (12.27 ±0.84) ug · mL-1 to (3.25 ±0.14) ug · mL-1.Reverse ratio is 3.78.Half inhibitory concentration of CDDP on SMMC-7721/VCR cell is from (20.42 ± 0.18) μg · mL-1 to (6.98 ±0.99) μg · mL-1,reverse ratio is 2.93.Half inhibitory concentration of 5-FU on SMMC-7721/ VCR cell is from (35.21 ± 0.68) μg · mL-1 to (18.27 ± 2.18) ug · mL-1;reverse ratio is 1.93.Compared with the effect on SMMC-7721 ceils,VCR,CDDP,5-FU effect on SMMC-7721/VCR cells had significant difference (P ＜0.01).Compared with the effect on SMMC-7721/VCR cell which was dealed by Tanshinone Ⅱ A microemulsion,VCR,CDDP,5-FU effect on SMMC-7721/VCR cells had significant difference (P ＜ 0.01).Conclusion The Tanshinone Ⅱ A submicroemulsion can inhibit the growth of SMMC-7721 cells and SMMC-7721/VCR cells.The Tanshinone Ⅱ A submicroemulsion can partially reverse the multidrug resistance of SMMC-7721/VCR in vitro.

In order to find highly active antidiabetic lead compound, sixteen 4-aminobenzoic acid derivatives were designed and synthesized directly through Mannich reaction in the solution of ethanol at 15-35 degrees C with facile method, mild reaction condition and high yield (45%-90%). Fifteen of them are new compounds. Their structures were confirmed by 1H NMR, 13C NMR, IR, ESI-MS and HR-MS. Alpha-glucosidase inhibitory activity of these compounds indicated that most of these compounds possess the activity with the order: 2c > 2b > 2h > 1a > 1f. The structure-activity relationship of these 4-aminobenzoic acid derivatives was also discussed.
4-Aminobenzoic Acid ; chemical synthesis ; pharmacology ; Drug Design ; Glycoside Hydrolase Inhibitors ; Hypoglycemic Agents ; chemical synthesis ; pharmacology ; Mannich Bases ; chemistry ; Molecular Structure ; Structure-Activity Relationship ; alpha-Glucosidases ; metabolism ; para-Aminobenzoates

OBJECTIVETo evaluate the immunostimulatory capacity of human peripheral blood dendritic cells (DCs) with Her2/neu gene transfection mediated by adeno-associated virus.

METHODSThe HLA genotypes of the breast cancer cells SK-BR-3 and MCF7 were determined, and the mononuclear cells from healthy donors with matching HLA genotype were isolated by Ficoll-Hypaque density gradient separation. The isolated cells were divided into two groups with or without transfection with the recombinant virus harboring Her2/neu gene. The cells were cultured for 7 days in RPMI 1640 medium supplemented with 10% AB human serum, GM-CSF, interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-alpha). The mature DCs were then harvested from the cell culture and their phenotypes were identified using flow cytometry. MTT assay was employed to examine the specific killing activity of the T cells induced by the DCs.

RESULTSThe DCs transfected with the recombinant adeno-associated virus expressed CD1a, CD86 and CD83 at the rate of 98.10%, 99.42%, and 84.59%, and those without the viral transfection expressed the markers at the rate 92.69%, 98.07%, and 82.72%, respectively, showing no obvious differences in the phenotypes of the two DCs. The transfected DCs, however, showed markedly higher expression rates of CD40 and CD80 than the non-transfected DCs (61.02% vs 36.19%, and 97.61% vs 55.5%, respectively). The DCs, irrespective of the transfection, showed comparable capacities in stimulating T cell proliferation. The transfected DCs exhibited the capacity of inducing the T cells to specifically kill the target tumor cells, with the highest killing rate of (39.7-/+7.2)%.

CONCLUSIONThe immunostimulatory capacity of human peripheral blood DCs are enhanced by Her2/neu gene transfection mediated by adeno-associated virus.

Breast Neoplasms ; pathology ; Cell Line, Tumor ; Cells, Cultured ; Dendritic Cells ; cytology ; immunology ; metabolism ; Dependovirus ; genetics ; metabolism ; Genes, erbB-2 ; genetics ; Genetic Vectors ; Granulocyte-Macrophage Colony-Stimulating Factor ; pharmacology ; Humans ; Leukocytes, Mononuclear ; cytology ; Receptor, ErbB-2 ; biosynthesis ; genetics ; Recombinant Proteins ; genetics ; immunology ; metabolism ; Transfection

Due to long-term use of immunosuppressive agents, solid organ transplant recipients (SOTR) belong to high-risk populations of multiple pathogenic infection, including SARS-CoV-2. In addition, SOTR are constantly complicated by chronic diseases, such as hypertension and diabetes mellitus, etc. After infected with SARS-CoV-2, the critically ill rate and fatality of SOTR are higher than those of the general population, which captivates widespread attention from experts in the field of organ transplantation. Omicrone variant is currently the significant pandemic strain worldwide, rapidly spreading to more than 100 countries worldwide and causing broad concern. According to the latest international guidelines on the diagnosis and treatment of SARS-CoV-2 infection and relevant expert consensus in China combined with current domestic situation of SARS-CoV-2 pandemic and China's "diagnosis and treatment regimen for SARS-CoV-2 infection (Trial Version 10)", the epidemiology, clinical manifestations and prognosis, diagnosis, clinical classification and treatment of SARS-CoV-2 infection were briefly reviewed.