Biomedical subjects

Jun-Hao Chen

Publications and source records attributed to Jun-Hao Chen.

5 recordsLinked to original sources

PubMed2004

Inhibitory effects of flavonoids on phosphodiesterase isozymes from guinea pig and their structure-activity relationships.

The structure-activity relationships of flavonoids with regard to their inhibitory effects on phosphodiesterase (PDE) isozymes are little known. The activities of PDE1-5 were measured by a two-step procedure using cAMP with [(3)H]-cAMP or cGMP with [(3)H]-cGMP as substrates. In the present results, PDE1, 5, 2, and 4 isozymes were partially purified from guinea pig lungs in that order, and PDE3 was from the heart. The IC(50) values of PDE1-5 were greater than those reported previously for the reference drugs, vinpocetin, EHNA, milrinone, Ro 20-1724, and zaprinast, by 5-, 5-, 7-, 5-, and 3-fold, respectively. As shown in Table 2, luteolin revealed non-selective inhibition of PDE1-5 with IC(50) values in a range of 10-20 microM, as did genistein except with a low potency on PDE5. Daidzein, an inactive analogue of genistein in tyrosine kinase inhibition, showed selective inhibition of PDE3 with an IC(50) value of around 30 microM, as did eriodictyol with an IC(50) value of around 50 microM. Hesperetin and prunetin exhibited more-selective inhibition of PDE4 with IC(50) values of around 30 and 60 microM, respectively. Luteolin-7-glucoside exhibited dual inhibition of PDE2/PDE4 with an IC(50) value of around 40 microM. Diosmetin more-selectively inhibited PDE2 (IC(50) of 4.8 microM) than PDE1, PDE4, or PDE5. However, biochanin A more-selectively inhibited PDE4 (IC(50) of 8.5 microM) than PDE1 or PDE2. Apigenin inhibited PDE1-3 with IC(50) values of around 10-25 microM. Myricetin inhibited PDE1-4 with IC(50) values of around 10-40 microM. The same was true for quercetin, but we rather consider that it more-selectively inhibited PDE3 and PDE4 (IC(50) of < 10 microM). In conclusion, it is possible to synthesize useful drugs through elucidating the structure-activity relationships of flavonoids with respect to inhibition of PDE isozymes at concentrations used in this in vitro study.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2004

Abdominal aorta transplantation after programmed cryopreservation.

AIM: To study the morphologic and cellular immunologic changes after homologous transplantation of the abdominal aorta in rats after programmed cryopreservation (-196 degrees). METHODS: Abdominal aorta was harvested from anesthetized Spraque Dawley (SD) rats for cryopreservation (group B) or immediate implantation (group A). The survival rates and apoptotic rates of aortic endothelial cells (ECs) were examined. The patency rates, histology and cellular immunologic changes of the abdominal aorta were examined on days 1, 3, 7, 14, 30, 60 after transplantation respectively. RESULTS: The survival rate of ECs after programmed cryopreservation was 90.1+/-1.79%, about 3.4% lower than that of uncryopreservation (93.5+/-1.96%). The apoptotic rates of ECs was increased after cryopreservation (7.15% vs 4.86%, P<0.05). The patency rate of group B was significantly higher than that of group A (91.6+/-12.9% vs 62.5+/-26.2%, P<0.01). CD4/CD8 ratio, TCR alpha beta and CD11b/CD18 ratio of group B were significantly lower than those of group A (P<0.05). Revivification of the cryopreserved abdominal aorta showed normal adventitia and intact smooth muscle cells. CONCLUSION: Cryopreservation can reduce homologous abdominal aortic antigenecity. Even if without administration of immunosuppressive agents, it is still feasible to implement homologous artery grafting in rats.

Animals↗

PubMed2004

Suppressive effects of 3-O-methylquercetin on ovalbumin-induced airway hyperresponsiveness.

Rhamnus nakaharai Hayata (Rhamnaceae) has been used as a folk medicine in Taiwan for treating constipation, inflammation, tumors, and asthma. 3-O-Methylquercetin (3-MQ), a main constituent of the plant, has been reported to inhibit total cAMP- and cGMP-phosphodiesterase (PDE) of guinea pig trachealis at low concentrations. 3-MQ has been also reported to more selectively inhibit PDE3 than PDE4 with a low K(m) value. Therefore we were interested in investigating its suppressive effects on ovalbumin (OVA)-induced airway hyperresponsiveness in vivo and in vitro. 3-MQ (3-30 micromol/kg, i. p.) significantly suppressed the enhanced pause (Penh) value induced by aerosolized methacholine (50 mg/mL) in sensitized mice after secondary allergen challenge. 3-MQ (3-30 micromol/kg, i. p.) also significantly suppressed total inflammatory cells, macrophages, neutrophils, and eosinophils, but not lymphocytes. In addition, 3-MQ (3 micromol/kg, i. p.) significantly decreased the secretion of TNF-alpha, and at the highest dose (30 micromol/kg, i. p.) even decreased the secretions of IL-4, IL-5, and TNF-alpha. 3-MQ (1-10 microM) as well as Ro 20-1724 (3-30 microM), a selective PDE4 inhibitor, significantly attenuated OVA (100 microg/mL)-induced contractions. 3-MQ (30 microM) as well as milrinone (1-10 microM), a selective PDE3 inhibitor, significantly enhanced baseline contractions in isolated guinea pig left and right atria. However, neither 3-MQ nor milrinone significantly affected baseline beating rate in the right atria. 3-MQ (3-30 micromol/kg, i. p.) did not significantly affect systolic pressure in conscious mice. In conclusion, 3-MQ has both anti-inflammatory and bronchodilating effects, and has the potential for use in the treatment of asthma at a dose without affecting blood pressure.

Animals↗

PubMed2004

[Immunophenotype analysis in 121 patients with lymphoproliferative diseases by flow cytometry].

BACKGROUND & OBJECTIVE: Multiple parameter immunophenotype analysis by flow cytometry (FCM) could improve the accuracy of diagnosis in lymphoproliferative diseases. This study was to analyze the immunophenotype of 135 samples, including lymph nodes, blood, bone marrow, and cerebrospinal fluid samples, from 121 patients with suspected lymphoid malignancies, to evaluate its role in diagnosis. METHODS: All samples were tested by routine morphological, pathological, and immunohistochemical methods, and analyzed by FCM in suspended single cells, to compare the accuracy of different diagnostic methods. RESULTS: (1) Three of 23 lymph nodes, which failed to be diagnosed by routine methods, were determined by flow cytometric immunophenotype analysis. (2) According to new WHO classification, 96 of 97 blood or bone marrow aspiration samples were diagnosed by flow cytometric immunophenotype analysis, while 88 of 97 samples were diagnosed by routine immunohistochemical method. (3) Multiple parameter immunophenotype analysis in cerebrospinal fluid samples by FCM improved the diagnostic accuracy of leukemia or lymphoma involvement of central nervous system. CONCLUSIONS: Multiple parameter immunophenotype analysis by FCM improves the accuracy of diagnosis in lymphoid malignancies, and can be used in diagnosis, differentiated diagnosis, and detection of minimal residue in lymphoproliferative diseases.

Adolescent↗

PubMed2003

3-O-methylquercetin more selectively inhibits phosphodiesterase subtype 3.

Rhamnus nakaharai Hayata (Rhamnaceae), has been used as a folk medicine in Taiwan for treating constipation, inflammation, tumors and asthma. 3-O-methylquercetin (3-MQ), a main constituent of the plant, has been reported to inhibit total cAMP- and cGMP-phosphodiesterase (PDE) of guinea pig trachealis. Therefore we were interested in investigating the inhibitory effect of 3-MQ on various PDE isozymes from guinea pig lungs and hearts. Isolated guinea pig lungs and hearts were homogenized and centrifuged. The supernatant was chromatographed over a column of Q-sepharose, and eluted with various concentrations of NaCl. In the following order, PDE subtypes 1, 5, 2, 4 from lungs, and 3 from hearts were separated. The IC 50 values of 3-MQ on these isozymes were 31.9, 86.9, 18.6, 28.5 and 1.6 microM, respectively. 3-MQ (10-100 microM) non-competitively inhibited PDE2, but competitively inhibited PDE4. 3-MQ (1-10 microM) also competitively inhibited PDE3. However, 3-MQ (10-100 microM) did not competitively inhibit PDE1 and 5, although it had a tendency to competitively inhibit PDE1 at concentrations of 10 - 30 microM. The present results showed that K i value of 3-MQ was similar to that of milrinone in PDE3, and was not significantly different from that of Ro 20 - 1724 in PDE4, respectively. In conclusion, 3-MQ was revealed to be a selective and competitive PDE3/PDE4 inhibitor, although its inhibitory effect on PDE4 was not potent. Therefore, 3-MQ may have a potential in the treatment of asthma beside its antiviral activity.

Animals↗