Biomedical subjects

Hong Liu

Publications and source records attributed to Hong Liu.

At least 109 records · Page 6Linked to original sources

PubMed2006

[Efficiency and characteristic of biological activated carbon fluidized bed for oil-field wastewater treatment].

In order to find method to improve biodegradation of oil-field wastewater, the biological activated carbon fluidized bed (BAC-FB) process for oil-field wastewater treatment in aerobic condition is studied. The results show that the process demonstrated highest removal rate with hull activated carbon (AC) as carrier and carrier concentration of 15%. The optimized HRT of the process is 5 h. COD, UV254, UV410, organic acid and organic compounds (GC/MS) were detected as the index to indicate the efficiency of oil-field wastewater treatment by this process. The results show that the removal rate of COD range from 25% to 45%. The average removal rate of UV254, UV410, organic acid is 85.9%, 73.6%, 51.5% respectively. The removal rate of oil content is almost 100%. However, alkane is difficult to remove from wastewater. Furthermore, high concentration inorganic materials such as calcium, chlorine were found to accumulate on activated carbon during treatment process, which is harm to adsorption and biodegradation of organic compound. High temperature of oil-field wastewater is also one of factors to inhibit adsorption and biodegradation of organic compound.

Bacteria, Aerobic↗

PubMed2006

[Etiologic and relevant factor analysis of 1,622 ESRD patients with hemodialysis in Hunan province].

OBJECTIVE: To analyze the etiology and the relevant factors such as age, sex, blood pressure, outcomes and causes of death in end stage renal disease (ESRD) with hemodialysis (HD) in some hospitals in Hunan province. METHODS: The retrospective analysis included 1,622 ESRD with HD patients. Data on the etiology, demographic and epidemiologic aspects of these patients were examined, and life expectancy and mortality rate were calculated. RESULTS: In 1,622 ESRD with HD patients, the average age at the start of HD was 46.91 +/- 15.41, and the male/female ratio was 1.45/1. As the leading cause, chronic glomerulonephritis accounted for 56.43%, followed by hypertensive nephropathy (12.58%), obstructive nephropathy (9.13%) and diabetic nephropathy (8.85%). In recent years, the constituent ratio of diabetic nephropathy rose. The number of ESRD maintenance HD (MHD) patients was 581. Among them, 43.7% remained MHD, 13.0% received renal transplantation, 19.9% were transferred to other hospitals for HD, 7.2% became peritoneal dialysis, 14.8% died, and 1.4% ceased treament for economic reasons. The longest MHD was 13 years. The 1st-year, 3rd-year and 5th-year survial rate of MHD patients was 93.53%, 68.92% and 62.51%, respectively. The leading cause of death was cardiovascular incidence. In this group of ESRD with (53.6%), and then cerebrovascular disorder (21.0%). CONCLUSION: HD patients, the age of starting dialysis was 30 approximately 70. The first cause was chronic glomerulonephritis. As the age increased, the constituent ratio of diabetic nephropathy rose. In MHD patients, the 1st-year, 3rd-year and 5th-year survial rate of maintenance hemodialysis patients was 93.53%, 68.92% and 62.51%, respectively. The first cause of death was cardiovascular accidence, and then cerebrovascular disorder.

Adult↗

PubMed2006

[Surface enhanced Raman scattering spectra of phytic acid in the sol silver oxide].

Surface enhanced Raman scattering spectra of phytic acid were recorded in the sol oxide silver. Based on ab-initio/ STO-3 quantum calculations results, assignments to the vibrational modes of phytic acid were carried out. On the basis of the mechanism of SERS, the adsorption modes were suggested that phytic acid chemically adsorbed on the oxide silver surface through four phosphate bonds.

English Abstract↗

PubMed2006

[In vitro effect of all-trans retinoic acid on cell adhesion molecule expression and adhesion capacity of bone marrow stromal cells in patients received peripheral blood stem cell transplantation].

The aim of this study was to evaluate the effect of all-trans retinoic acid (ATRA) on cell adhesion molecule expression and adhesion capacity of bone marrow stromal cells (BMSC) in patients after conditioning treatment for peripheral blood stem cell transplantation (PBSCT). BMSC of 27 patients before and after conditioning treatment for PBSCT were cultured in vitro. After treated with ATRA at 0.01, 0.1, or 1 micromol/L, expression of intercellular adhesion molecule-1 (ICAM-1) protein and vascular adhesion molecule-1 (VCAM-1) protein were detected by flow cytometry, and soluble ICAM-1 (sICAM-1) protein was determined by using radioimmunoassay. Then BMSC was co-cultured with CD34+ cells, and adhesion rate of BMSC to CD34+ cells was measured. The results showed that after pretreatment with conditioning regimen for PBSCT, the expressions of ICAM-1 and VCAM-1 proteins in BMSC and the expression level of sICAM-1 protein in supernatant of BMSC culture were down-regulated, and the adhesion rate of BMSC to CD34+ cells was decreased, after administration of ATRA, the expression of ICAM-1 protein in BMSC, sICAM-1 protein in culture medium and adhesion rate of BMSC to CD34+ cells all increased significantly, but expression of VCAM-1 protein changed no significantly. It is concluded that the ATRA can partly restore adhesion function of BMSC injured by pretreatment for PBSCT and contribute to hematopoietic reconstitution.

Adolescent↗

PubMed2006

[High-level expression behaviors of recombinant human interferon omega in logarithm phrase Pichia pastoris].

Expression difference of heterologous recombinant protein in Pichia pastoris with different specific growth rate (mu) was observed. The expression conditions of recombinant human interferon omega (rhIFN(omega)) in logarithm phrase Pichia pastoris with higher mu were optimized by shake flask tests under various initial pH, methanol concentration, duration of the induction, cell density, and medium volume. The results showed that there were prominent influences of mu on expression of rhlFN(omega). The maximum yield of rhIFN(omega) in the Pichia pastoris with mu of 0.1612 h(-1) was 558 mg/L. However, these in the Pichia pastoris with mu of 0.1321, 0.0505 and 0.0052 h(-1) were reduced by 50%, 68% and 99%, respectively. In 250 mL shake flask, the optimal medium volume, cell density, initial pH, methanol concentration, frequency and duration of methanol induction were 30 mL, 200 - 300 g/L (WCW), natural, 15 g/L, 1 time in every 24h and 4d, respectively. Under the optimal expression condition, the maximum yield of rhIFN(omega) in logarithm phrase Pichia pastoris was 1070 mg/L which was increased by 149% more than that under the initial condition.

Cell Count↗

PubMed2006

[Effects of high glucose on the cell proliferation, damage and cytokine in human peritoneal mesothelial cells].

OBJECTIVE: To determine the mechanism of peritoneal fibrosis of peritoneal mesothelial cells by high glucose. METHODS: The third passage human peritoneal mesothelial cells (HPMCs) from primary culture were divided into a control group (F(12)) and high glucose groups (F(12)+4% glucose) in different times (24, 48 h). The cell proliferation was assayed by the method of MTT (methylthiazoletetrazolium). The cell damage was measured by LDH (lactate dehydrogenase). The protein expression of fibronectin (FN), transforming growth factor-beta1(TGF-beta(1)) and connective tissue growth factor (CTGF) were detected by ELISA. The mRNA expression of FN, TGF-beta(1) and PAI-1 were detected by RT-PCR. RESULTS: High glucose suppressed the cell proliferation. The result of MTT showed that compared with the control group, the value of OD of high glucose groups at 24 or 48 h decreased significantly (P<0.01 or 0.01); The cell damage was enhanced in high glucose groups, at 24 or 48 h compared with the control group at the same time (all P<0.01). The protein expressions of TGF-beta(1), CTGF and FN in supernate fluid of cell culture were significantly enhanced when high glucose stimulated the HPMCs in the high glucose groups at 24 or 48 h compared with the control group at the same time (P<0.05 or 0.001). The expressions of FN, TGF-beta(1) and PAI-1 mRNA were upregulated in 24 h high glucose group compared with that of 24 h control group. CONCLUSION: High glucose can suppress the HPMC proliferation and damage HPMCs. Increase of TGF-beta(1), CTGF, FN and PAI-1 of HPMCs stimulated by high glucose can promote the synthesis and decreased degradation of extracellular matrix, which might be related with the mechanism of peritoneal fibrosis of peritoneal mesothelial cells by high glucose.

Cell Proliferation↗

PubMed2006

Cooperative effect of gefitinib and fumitremorgin c on cell growth and chemosensitivity in estrogen receptor alpha negative fulvestrant-resistant MCF-7 cells.

The selective ER downregulator, fulvestrant, is currently approved as a second line endocrine therapy after onset of resistance to prior antiestrogen therapy in postmenopausal breast cancer patients. Resistance to antihormonal therapies is common and, therefore, we anticipate that fulvestrant-resistance will occur as well. The current study was undertaken to investigate the underlying molecular changes after fulvestrant-resistance and find new therapeutic targets and agents for fulvestrant-resistant breast cancer cells. We developed a unique fulvestrant-resistant cell line (MCF-7/F), derived from MCF-7 estrogen receptor alpha (ERalpha)-positive human breast cancer cells, by culturing them in 1 microM fulvestrant containing medium for approximately 18 months. MCF-7/F cells became irreversibly ERalpha negative as withdrawal of fulvestrant did not alter the ERalpha-negative phenotype, determined by real-time PCR, Western blot analysis, and ERE-luciferase transfection assays. MCF-7/F cells grew in a hormone-independent manner. Interestingly, MCF-7/F cells overexpressed both epidermal growth factor receptor (EGFR) and breast cancer resistant protein (BCRP). Gefitinib, a specific EGFR tyrosine kinase inhibitor, preferentially inhibited the growth of MCF-7/F cells relative to MCF-7 cells by inhibiting both MAPK44/42 and Akt phosphorylation. MCF-7/F cells became less sensitive to chemotherapeutic agents such as mitoxantrone. Moreover, fumitremorgin C, a specific BCRP inhibitor, significantly increased the efficacy of mitoxantrone in MCF-7/F cells. Gefitinib increased the inhibitory effect of mitoxantrone on cell growth. Similarly, fumitremorgin C increased the inhibitory effect of gefitinib on cell growth, suggesting that there is a bidirectional crosstalk between EGFR and BCRP. More importantly, these results provide a molecular basis for using gefitinib, BCRP inhibitors, and chemotherapeutic agents as combination therapy approaches in fulvestrant-resistant breast cancer.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

PubMed2006

[Study on cadmium absorption in pumpkin by atomic absorption spectrophotometry].

A study was carried out on the characteristic of cadmium absorption in pumpkin by atomic absorption spectrophotometer. The results show that the cadmium absorption amount in pumpkin increased with the increase in cadmium concentration. Meanwhile the cadmium absorption amount in pumpkin increased with time. Eight hours after being cultured in the liquid, the cadmium absorption amount became saturated. The cadmium absorption rate reached the peak after 2 hours, then the absorption rate gradually reduced. The cadmium absorption amount in pumpkin is less in acid or alkali compared with neutral condition. And the absorption amount became minimum in pH 3, while maximum in pH 7.

Absorption↗

PubMed2006

[Determination of periplocin in different parts of Periploca sepium].

OBJECTIVE: To determinate the content of periplocin in different parts of Periploca sepium Bunge. METHODS: HPLC were carried out on ODS column, acetonitril: water (27: 73) as mobile phase, detection wavelength at 220nm. RESULTS: The content of periplocin in root bark, stem bark, xylem of root, xylem of stem are 1.03%, 0.65%, 0.26%, 0.39% respectively. No periplocin was detected in leaves and fruit. CONCLUSION: The plant of Periploca sepium Bunge should be multiply utilized.

Chromatography, High Pressure Liquid↗

PubMed2006

[Preparation of puerarin solid self-microemulsion].

OBJECTIVE: To prepare puerarin solid self-microemulsifying drug delivery system (SMEDDS). METHODS: Pseudo-ternary phase diagram was used to select the formula of microemulsion. The self-microemulsification efficiency was assessed, such as viscosity, conductance, refraction, zeta potential, size ditribution, dissolution were investigated. Puerarin were determined by UV to calculate the cumulative release at different time. RESULTS: The optimum formulation of puerarin solid self-microemulsifying drug delivery system the consisted of puerarin-Tween 800 glycerinum-ethyl oleate-water-Gum Acacia-manicol at weight ratio of 1.7: 16. 6: 16. 6: 16. 6 : 1.3: 4.0: 39.9: 19.9; Average particle diameter was 30 nm; The dissolution was 94.29% at 10 min. CONCLUSION: Stability of puerarin solid self-microemulsion drug delvery system is good, potent in improving the dissolution of puerarin.

Biological Availability↗

PubMed2006

[Treatment of domestic wastewater using sequence batch reactor enhanced by low intensity ultrasound].

Enhancement effect of ultrasound (US) on the bio-treatment of domestic wastewater was studied through contrast experiments between two sequence batch reactors (SBR) with and without US. The results showed that when US with intensity of 0.3 W x cm(-2) was employed to irradiate 10% of the activated sludge in the SBR for 10 minutes every 8 hours, the removal rate of COD was improved by 3% - 6%, and the effluent COD of US-SBR was lower than that of the control SBR by 40% - 53%. Moreover, the tolerance of SBR to high concentration and toxicity impact was improved effectively. For the practical domestic wastewater, the sludge activity was 14% higher in the US-SBR than that in the control SBR, increasing the capacity of microorganism to degrade the refractory compounds. The settleability of activated sludge in the US-SBR descended slightly and 5% increase of SVI (sludge volume index) was observed during the experiment, but it had little influence on the system since the increment was very small. According to the results of scan electro-microscope (SEM) and microbial community structures analysis, the microorganism in the US-SBR was damaged by US and compared with the control, the cell wall was ruffled obviously, but it didn't change the community structures of activated sludge. Kinetics analysis of microbial respiration in the two SBRs showed that the activated sludge in the US-assisted SBR could make better use of substrate.

Bacteria↗

PubMed2006

[Clinical and pathologic characteristics of primary angiosarcoma of breast].

OBJECTIVE: To study the clinical and pathologic characteristics of primary angiosarcoma of breast. METHODS: Five cases of primary angiosarcoma of breast were reviewed. Immunohistochemical study (SP method) for factor VIII-related antigen, CD31, CD34, estrogen receptor, progesterone receptor and c-erbB-2 was performed. The clinical data were also analyzed. RESULTS: All of the 5 patients had a history of a painless breast lump. Ultrasound examination and mammogram did not reveal any specific findings. Histologically, various degree of cellular pleomorphism was noted. Immunohistochemical study showed a positive expression of endothelial associated antigens of the tumors cells in all the 5 cases. The staining result for estrogen receptor, progesterone receptor and c-erbB-2 was negative. CONCLUSIONS: Primary angiosarcoma of breast is a rare entity. The diagnosis is rather difficult owing to the lack of specific clinical findings and histological heterogeneity. Application of Positive expression of endothelial associated antigens of the tumors cells is helpful in making a pathological diagnosis morphologically.

Adult↗

PubMed2006

[Study on crossed and uncrossed disparity evoked potential of dynamic random dot stereogram].

OBJECTIVE: To analyze the disparity evoked potentials (DEP) of fine disparities, coarse disparities, crossed disparities and uncrossed disparities and provide parameters of impersonal examining stereopsis. METHODS: A software package for generating dynamic random dot stereogram (DRDS) was developed as a visual stimulus to elicit DEP in 30 normal subjects. The DEP of every subject was recorded in different crossed and uncrossed disparity stimuli (4', 8', 15', 23', 30', 45', 53', 60', 72', 87', 102', 124', 150' of arc). RESULTS: (1) the constant negative-positive complex wave was observed in different disparity stimuli. (2) The N wave's latency of -45' was the longest, the N wave's latency of -150' was the shortest among crossed disparities. The N wave's latency of 4', 23' was the longest, the N wave's latency of 124' was the shortest among uncrossed disparities. (3) The amplitude peak of P wave occurred at -23', -60', -150' among crossed disparities. The amplitude peak of P wave occurred at 15', 45', 72' among uncrossed disparities. (4) All characteristic crossed disparities were smaller than the uncrossed disparities. The change orderliness of small crossed disparities was different from that of small uncrossed disparities. CONCLUSIONS: The N wave's latency and the P wave's amplitude can be used as parameters to impersonally examine stereopsis. These results suggest that stereopsis can be divided into fine crossed stereopsis, fine uncrossed stereopsis, coarse crossed stereopsis, and coarse uncrossed stereopsis.

Adolescent↗

PubMed2005

Connective tissue growth factor-mediated angiotensin II-induced hypertrophy of proximal tubular cells.

BACKGROUND: Cellular hypertrophy is an early, important pathological feature of renal diseases such as diabetic nephropathy and remnant kidney. Recent studies have demonstrated that angiotensin II (AngII) plays a key role in mediating cell hypertrophy. The aim of our work was to explore the role of connective tissue growth factor (CTGF) in mediating AngII-induced tubular cell hypertrophy in vivoandin vitro. METHODS: In an in vivo study, male Sprague-Dawley rats were randomly divided into three groups: control rats, diabetic rats and diabetic rats treated with irbesartan (IRB). The index of kidney hypertrophy (kidney weight/body weight, KW/BW), glomerular tuft area (AG), glomerular tuft volume (VG) and proximal tubular area (AT) were determined. Renal expression for CTGF was detected by immunohistochemical staining. In an in vitro study, the influence of CTGF antisense oligonucleotide (CTGF AS) on AngII-induced CTGF expression and cell hypertrophy was also investigated. RESULTS: In an in vivo study, diabetic rats showed a significant increase of KW/BW, AG, VG, and AT from week 1 onwards compared to normal control, which could be significantly inhibited by using IRB. Furthermore, there was a significantly increasing expression of CTGF in both glomeruli and tubuli in diabetic rats compared to control, and the extent of CTGF expression closely correlated with the severity of renal hypertrophy. Treatment with IRB could markedly inhibit the renal expression of CTGF. In an in vitro study, AngII stimulated the expression of CTGF mRNA and CTGF protein. AngII significantly increased the total protein content in HK2 cells, which was markedly inhibited by co-treatment with CTGF AS. The average cellular diameter determined by scanning electronic microscope showed that the increase of cell size induced by AngII could be significantly inhibited by CTGF AS. Furthermore, flow cytometer study showed that AngII arrested the cell cycle in the G0-G1 phase, which was significantly reversed by treatment with CTGF AS. CONCLUSION: Our data provide both in vivo and in vitroevidence that CTGF is involved in mediating AngII-induced renal hypertrophy.

Angiotensin II↗

PubMed2005

Ultrasonic frequency effects on the removal of Microcystis aeruginosa.

Algae bloom in source water causes high chemical consumption and deteriorates water quality in waterworks. This paper studied the ultrasonic removal of Microcystis aeruginosa. The results showed that algae cells could be effectively removed by sonication and gas vesicle collapse was the main mechanism. The ultrasonic algae removal followed the first order reaction with a rate constant of 0.023 min(-1) (80 W, 80 kHz). Higher ultrasound frequency benefited algae removal; the algae removal rate constant was 0.114 min(-1) at 1320 kHz and 0.0224 min(-1) at 20 kHz (80 W). Higher ultrasound power also accelerated algae removal; the algae removal rate constant was 0.023 min(-1) at 80 W and 0.007 min(-1) at 32 W (80 kHz). However, high ultrasound power and long irradiation caused microcystins to increase. 80 W, 80 kHz sonication for 5 min increased the extracellular microcystins concentration from 0.87 microg/L to 3.11 microg/L. Sound frequency had little impact on the microcystins release. The chlorophyll a concentration initially decreased and then stabilized after 5 min of sonication.

Chemistry↗

PubMed2005

Age-related changes of serum bone alkaline phosphatase and cross-linked C-telopeptides of type I collagen and the relationship with bone mineral density in Chinese women.

BACKGROUND: Previous studies have shown that bone turnover rate changes with age. At the same time, there is no definitive research regarding age-related changes of bone turnover level and its association with bone mineral density (BMD) in Chinese mainland women. METHODS: In a cohort of 663 Chinese mainland women aged 20-70 years, serum bone alkaline phosphatase (BAP) and serum cross-linked C-telopeptides of type I collagen (sCTX) were measured to evaluate the state of bone formation and resorption, respectively. BMD was measured in the posteroanterior spine, supine lateral spine, hip and forearm using a dual-energy X-ray absorptiometry. RESULTS: The cubic polynomial regression model best fit age-related changes in serum BAP (R2=0.398, p<0.001) and sCTX concentrations (R2=0.148, p<0.001) with largest R2 from comparison 8 different regression models. Their values reached a minimal level in the 30-39 years age group, and increased dramatically in the 40-59 years groups. There was a decreasing trend of BAP in women >60 years. The levels of BAP and sCTX were inversely correlated to BMD in various skeletal regions over the entire population (r=-0.096 to -0.357, p<0.05). sCTX was a significant predictor of a T-score< or =-2.5 of BMD in postmenopausal women with sCTX levels above mean+2 SD of women aged 30-39 years compared with other postmenopausal women, which indicated by odds ratios 1.9-3.7 (p<0.05) for various skeletal regions, especially for the lateral lumbar spine (2.2, p<0.01), Ward's triangle (3.7, p<0.01), and ultradistal end of radius + ulna (2.8, p<0.001). CONCLUSIONS: Age-dependent serum BAP and sCTX were inversely correlated to BMD, and sCTX was a useful parameter for the prediction of a low T-score of BMD at skeletal sites with abundant cancellous bone in postmenopausal women.

Adult↗

PubMed2005

[Dendritic cells reduce the number and function of CD4+CD25+ cells in cytokine-induced killer cells].

OBJECTIVE: To investigate the influence of dendritic cells (DCs) on the prevalence and function of regulatory T cells (Tregs) in cytokine induced killer (CIK) cells. METHODS: The blood samples of 20 patients with solid tumors were collected. The peripheral mononuclear cells (PBMCs) were isolated. CIK cells were added into the culture fluid without CD(4)(+)CD(25)(+)T cells (CIK-Treg(del) cells) and the culture fluid of regular PBMCs respectively, and the proliferation and cytotoxicity of the CIK cells were detected by BrdU method and with the cells of human lung carcinoma, breast carcinoma, colon carcinoma, and lymphoma as target cells respectively. CD(4)(+)CD(25)(+)T cells were added into another culture fluid of CIK-Treg(del) cells at the proportions of 20:1, 10:1, and 5:1 respectively, then the proliferation and cytotoxicity of the CIK cells were detected as described above. Flow cytometry was used to detect the surface markers of CIK cells. To identify the influence of DCs on the anti-tumor activity of CIK, PBMCs were isolated from the patients with solid tumor to culture the DCs and CIK cells. Dendritic cells were harvested on day 7 and co-cultured with the CIK cells (DC+CIK cells). The frequency of Tregs in CIK was determined by flow cytometry. The cytotoxicity was examined by LDH assay. The levels of TGF-beta, IL-10, IFN-gamma, IL-2, and IL-6 were analyzed by ELISA. RESULTS: The rates of the main effector cells in CIK cells (CD(3)(+)CD(56)(+) cells) were 17% +/- 5% and 28% +/- 5% in the regular CIK cells and CIK-Treg(del) cells respectively. LDH method showed that the cytotoxicity towards tumor cells of the CIK-Treg(del) cells The rates of the main effector cells in CIK cells (CD(3)(+)CD(56)(+) cells) were 17% +/- 5% and 28% +/- 5% in the regular CIK cells and CIK-Treg(del) cells respectively. LDH method showed that the cytotoxicity towards tumor cells of the CIK-Treg(del) cells was higher than that of the regular CIK cells (P < 0.05), however, after the addition of selected cells, the cytotoxicity of the CIK-Treg(del) cells decreased. Flow cytometry showed that the proportions of CD(4)(+)CD(25)(+) Treg cells in the CIK cells and DC-CIK cells were 13% +/- 5% and 10% +/- 4% respectively (t = 3.977, P = 0.001). After the DC induction the cytotoxicity of CIK cells was significantly higher than that of the regular CIK cells. ELISA showed that after DC induction the levels of TGF-beta and IL-10 of the DC+CIK group were significantly lower than those of the regular CIK cells (t = 2.136, P = 0.046; and t = 2.965, P = 0.008), and the level of IFN-gamma was significantly higher in the DC+CIK group (t = 2.220, P = 0.039). CONCLUSION: CD(4)(+)CD(25)(+) regulatory T cells inhibit the anti-tumor activity of CIK cells. The interaction between CIK cells and DCs is sufficient for the blockage of the properties of regulatory T cells. CIK cells have the desirable properties for immunotherapy approaches, especially after co-culture with DCs.

CD4-Positive T-Lymphocytes↗

PubMed2005

Discovering novel chemical inhibitors of human cyclophilin A: virtual screening, synthesis, and bioassay.

Cyclophilin A (CypA) is a member of cyclophilins, a family of the highly homologous peptidyl prolyl cis-trans isomerases (PPIases), which can bind to cyclosporin A (CsA). CypA plays critical roles in various biological processes, including protein folding, assembly, transportation, regulation of neuron growth, and HIV replication. The discovery of CypA inhibitor is now of a great special interest in the treatment of immunological disorders. In this study, a series of novel small molecular CypA inhibitors have been discovered by using structure-based virtual screening in conjunction with chemical synthesis and bioassay. The SPECS_1 database containing 85,000 small molecular compounds was searched by virtual screening against the crystal structure of human CypA. After SPR-based binding affinity assay, 15 compounds were found to show binding affinities to CypA at submicro-molar or micro-molar level (compounds 1-15). Seven compounds were selected as the starting point for the further structure modification in considering binding activity, synthesis difficulty, and structure similarity. We thus synthesized 40 new small molecular compounds (1-6, 15, 16a-q, 17a-d, and 18a-l), and four of which (compounds 16b, 16h, 16k, and 18g) showed high CypA PPIase inhibition activities with IC50s of 2.5-6.2 microM. Pharmacological assay indicated that these four compounds demonstrated somewhat inhibition activities against the proliferation of spleen cells.

Animals↗