ABSTRACT
@#Objective The potential mechanism of curcumin(CUR)combined with berberine(BBR)in improving drug-induced liver injury(DILI)was preliminarily predicted by a method of in vivo experiment in combination with network pharmacology.Methods The animal model was established by acetaminophen(APAP)-induced DILI and the levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were detected in serum of mice.The network pharmacological approach was used to collect related targets of CUR,BBR,and DILI;Wayne mapping was carried out to screen intersection targets,followed by establishment of a protein-protein interaction(PPI)network of CUR-BBR-DILI.Functional enrichment analysis of gene ontology(GO)and pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG)were conducted finally.Results The in vivo experimental results showed that the combination of CUR and BBR can significantly reduce the serum ALT and AST levels in mice,which is better than administration alone;Network pharmacology experiment results exhibited that 291 related targets of CUR and 208 related targets of BBR were collected by PharmMapper database,and 904 related targets of DILI were collected by Genecards database;77 intersection targets were screened by Venny 2.1.0 database;52 gene functions and 20 signal pathways possibly in connection with the improvement of DILI via drug combination were obtained by GO and KEGG analysis,respectively;nine of the top ten core targets according to degree in PPI network were enriched to PI3K/AKT signaling pathway,which were in order as follows:SRC,EGFR,HSP90AA1,IGF1,HRAS,MAPK14,ESR1,CASP3,and PTK2.Conclusion DILI might be synergistically improved by CUR combined BBR through multi-target and multi-pathway manner,providing a theoretical basis for the elucidation of the mechanism of drug combination against DILI.
ABSTRACT
Objective:To explore the innovation mode of independent transformation-oriented science and technology research program approval by medical new research & development (R&D) institution.Methods:Through analyzing the program layout, funds, review experts, undertaking units, chief experts and interdisciplinarity to summarize the experiences of the independent transformation-oriented municipal program approval by Haihe laboratory of Cell Ecosystem in 2022.Results:As a new medical R&D institution, which vigorously constructed by Tianjin, Haihe laboratory of Cell Ecosystem has carried out the practice of the independent transformation-oriented municipal program through the measures of layout of full-chain transformation, conducting transformation-oriented review, gathering high-level research talents, and emphasizing interdisciplinarity.Conclusions:The experiences of Haihe laboratory of Cell Ecosystem make significance for medical new R&D institutions to explore and cultivate scientific research program with transformation potential and to promote the transformation of scientific and technological achievements, which are powerful factors for new R&D institutions to play a role of pilot and provide important support to scientific and technological innovation and transformation.
ABSTRACT
Objective:To investigate the effect of polypeptide N-acetylgalactosaminaminyltransferase 2 (GALNT2) on the proliferation and apoptosis of human retinal vascular endothelial cells (HRCECs) cultured in high glucose and its possible mechanism.Methods:The small hairpin RNA (shRNA) targeting GALNT2 gene was constructed to interfere with the lentiviral vector and infect HRCECs.HRCECs were divided into blank control group, model group, NC-shGALNT2 group and shGALNT2 group, which were cultured in medium containing 5.5 mmol/L glucose, 25 mmol/L glucose, shGALNT2 negative control virus 25 mmol/L glucose and shGALNT2 knockdown virus 25 mmol/L glucose for 24 hours, respectively.The relative expression of GALNT2 mRNA in the four groups was detected by real-time fluorescence quantitative PCR.The relative expression levels of GALNT2, epidermal growth factor (EGF), EGF receptor (EGFR) and phosphorylated EGFR (p-EGFR) were detected by Western blot.The proliferative values of HRCECs were detected by cell counting kit-8 method.The apoptosis rate of different groups was detected by flow cytometry. Results:The relative expression levels of GALNT2 mRNA and protein were significantly higher in model group than in blank control group, and were significantly lower in shGALNT2 group than in blank control group (all at P<0.05). The cell proliferation value was significantly lower in model group than in blank control group, and was significantly higher in shGALNT2 than in model group and NC-shGALNT2 group (all at P<0.05). The apoptosis rates of blank control group, model group, NC-shGALNT2 group and shGALNT2 group were (4.73±0.26)%, (8.66±0.25)%, (9.26±1.12)% and (5.47±0.18)%, respectively, with a significant overall difference ( F=342.921, P<0.001). The apoptosis rate was significantly higher in model group than in blank control group, and was significantly lower in shGALNT2 group than in model group and NC-shGALNT2 group (all at P<0.05). The relative expression level of EGFR protein was significantly higher and the relative expression level of p-EGFR protein was significantly lower in model group than in blank control group (all at P<0.05). The relative expression of p-EGFR protein was significantly higher in shGALNT2 group than in model group (all at P<0.05). Conclusions:Knocking down GALNT2 can improve the proliferative ability of HRCECs under high glucose culture and reduce apoptosis, which may be related to the activation of EGFR signaling pathway.
ABSTRACT
Thyroid cancer is a common malignant tumor of the head and neck and endocrine system, characterized by high morbidity and low mortality. The main clinical challenge is the treatment of patients with advanced or high-risk thyroid cancer. At present, the study on the molecular pathogenesis of thyroid cancer provide new opportunities for thyroid cancer, including chemotherapy, molecular targeted therapy and immunotherapy.
ABSTRACT
Objective: To optimize the preparation technique for bifonazole suppositories and evaluate the quality.Methods: The appearance, hardness and melting time of suppositories were used as the evaluation indices to optimize the process conditions, such as suppository matrix, drug particle size, injection molding temperature and stirring conditions, etc.The content of bifonazole was determined by HPLC.Results: The best formula was as follows: the matrix was multiplicated monofatty glyceride-36, bifonazole was sieved by 100 mesh sieve and the best molding temperature was 45 ℃.The quality of the prepared suppositories with the above conditions was controllable in the appearance, melting time limit, hardness and content determination, etc.Conclusion: The formula of bifonazole suppositories is reasonable, the preparation process is feasible, and the quality control methods are reliable.