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Objective:High-throughput screening to obtain small molecular compounds against Gram-negative bacilli by targeting BamA outer membrane protein.Methods:The sybyl-X2.1 software was used to perform high-throughput virtual screening of small molecular compounds in Chemdiv compound library based on the molecular docking. The top 150 hits by high-throughput screening were re-screened through in vitro biological experiments. The top 4 small molecules with obvious antibacterial activity were selected for in-depth molecular docking analysis, and the small molecule 8308-0401 with the highest docking score was selected for further experiments. The antibacterial effect of 8308-0401 combined with rifampicin was tested by checkerboard assay. Finally, the affinity between 8308-0401 and BamA was tested by plasma surface resonance assay. Results:The docking score of the top 150 hits calculated by high-throughput virtual screening had a mean value of 5.63. In vitro biological experiments showed that small molecules 8308-0401, 8365-1335, C066-2507 and L582-0346 exhibited strong antibacterial activity. Among those molecules, 8308-0401 showed the highest molecular docking score, and synergistic antibacterial activity against both types of strains and clinical isolates when combined with rifampicin. 8308-0401 has a strong affinity to BamA with binding a constant of 182 μmol/L. Conclusion:The small molecule 8308-0401 exerts antibacterial activity against Gram negative bacilli by targeting the outer membrane protein BamA.
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Objective:To investigate the clinical characteristics and possible causes of transient spontaneous remission of childhood acute leukemia.Methods:The data of 3 children with acute leukemia who had transient spontaneous remission before standardized chemotherapy in Sun Yat-sen Memorial Hospital of Sun Yat-sen University in July 2018, May 2019 and October 2020 were collected. Moreover, the related influencing factors of spontaneous remission in leukemia were discussed by review of the literature.Results:All 3 children had fever at the onset of the disease, and they achieved transient spontaneous remission after anti-infection therapy. Case 1 obtained partial remission after the initial diagnosis of acute B lymphocytic leukemia (B-ALL), leukemia gene test showed E2A-PBX1 fusion, and relapsed after 12 days. Case 2 obtained spontaneous remission after the initial diagnosis of B-ALL, leukemia gene test showed p16 gene deletion and NRAS and EP300 genes mutation, and relapsed after 20 days. Case 3 obtained spontaneous remission after the initial diagnosis of acute monocytic leukemia, leukemia gene test showed MLL-ENL fusion and NRAS gene mutation, and relapsed after 30 days. A review of the literature showed that the main influencing factors of spontaneous remission in leukemia were Down syndrome, infection and blood transfusion. Other influencing factors included leukemia-related genes, termination of pregnancy and application of drugs.Conclusions:Transient spontaneous remission of childhood acute leukemia is rare in clinical practice, and the possible mechanism is related to infection-induced immune abnormalities. It is recommended that leukemia patients with spontaneous remission should be closely monitored for minimal residual disease.
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Objective To observe the ultrastructure of blood-brain barrier in the nude mouse model of brain me-tastases from lung cancer by transmission electron microscopy using lanthanum nitrate tracing.Methods PC-9 cells (1 × 106/0.1 mL) in logarithmic phase were respectively injected into six nude mice ( model group) selected from eight nude mice randomly via the left ventricle, the other two mice without any treatment as the control group.The general status of the mice was observed after implantation.In the fourth week all the mice were sacrificed and brain tissue samples were taken and prepared for transmission electron microscopic observation using lanthanum nitrate tracing.besides, the lung and brain were removed and stained with HE to detect the presence of tumor metastasis.Results Mice in the model group began to lose weight almost simultaneously in the third week and became moribund slowly, and were all sacrificed at the fourth week when showing clear signs of cachexia.At autopsy, the thoraxes were clear, with normal lungs.Histology showed evidence of brain metastasis in all the six mice.The electron microscopy showed that lathanum nitrate tracer was escaped from the capillaries and diffusely or sparsely distributed in the brain tissues of the model group mice, however lathanum nitrate tracer was still confined in the capillary lumen in the mice of control group.Conclusions The diffuse lathanum nitrate tracer in the brain parenchymal tissue indicates the impairment of blood-brain barrier in the nude mouse model of lung cancer brain metastasis and the formation of these metastases is accompanied with the destruction of blood brain barrier.
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Laboratory of electron microscopy is representative of large instruments laboratories in medical research.And the operation and management in this kind of laboratory are different.Case of forty years of operation and management in the medical laboratory of electron microscopy,this paper analyzed and summarized its successful experiences in the research management system,personnel system and the aspect of equipment maintenance management.Provide a management reference for medical research institutions with the laboratory of similar large-scale instruments.
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OBJECTIVE: We used the SD rat's bone marrow stromal cells (BMSCs) cultured in vitro to observe the effects of Bugu Mixture on the apoptosis and to explore the molecular biologic mechanism of the treatment of osteoporosis with Bugu Mixture. METHODS: BMSCs were separated from the bones of the extremities of SD rats in vitro. The morphologic changes, the apoptosis cell cycles, the mitochondrion membrane potential changes, and the Bcl-2 and Bax gene expression were observed, and the effects of Bugu Mixture on the course of cell apoptosis were evaluated. RESULTS: The earlier use of Bugu Mixture could decrease the cells blocked in G0/G1 phase, and promote their synthesis of DNA in S phase. The expression of Bcl-2 was higher in the Bugu Mixture group than that in the all-trans retinoic acid (ATRA) induced group, and the expression of Bax was lower in the Bugu Mixture group than that in the ATRA induced group. The mitochondrion membrane potential descended significantly in the Bugu Mixture group than that in the ATRA induced group. CONCLUSION: The mechanism of the treatment of osteoporosis with Bugu Mixture is that the earlier use of Bugu Mixture can decrease the amount of apoptostic cells induced by ATRA, thus promoting the cell mitosis and restraining the apoptosis. It can also act as a protector to Bcl-2 located on the mitochondrion membrane. By preventing the transferring of the Bax protein from cell-plasma to mitochondrion membrane, it takes the advantage of Bcl-2 in forming Bcl-2/Bax homodimer so as to prevent the opening of the permeability transition pore to avoid the changing of mitochondrion membrane potential and the destruction of biosynthesis caused by the mitochondrion release of apoptosis inducing factors and to reach the objective of restraining apoptosis.