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Biomedical subjects

J H Zheng

Publications and source records attributed to J H Zheng.

At least 19 recordsLinked to original sources

PU.1 phosphorylation correlates with hydroquinone-induced alterations in myeloid differentiation and cytokine-dependent clonogenic response in human CD34(+) hematopoietic progenitor cells.

The transcriptional regulatory factor PU.1 is important for the regulation of a diverse group of hematopoietic and myeloid genes. Posttranslational phosphorylation of PU.1 has been demonstrated in the regulation of a variety of promoters in normal cells. In leukemia cells, differing patterns of PU.1 phosphorylation have been described among acute myelogenous leukemia (AML) subtypes. Therefore, we hypothesized that modulation of PU.1-dependent gene expression might be a molecular mediator of alterations in myeloid cell growth and differentiation that have been demonstrated to be early events in benzene-induced leukemogenesis. We found that freshly isolated human CD34(+) hematopoietic progenitor cells (HPC) exhibit multiple PU.1-DNA binding species that represent PU.1 proteins in varying degrees of phosphorylation states as determined by phosphatase treatment in combination with electrophoretic mobility shift assay (EMSA). Maturation of granulocyte and monocyte lineages is also accompanied by distinct changes in PU.1-DNA binding patterns. Experiments reveal that increasing doses of the benzene metabolite, hydroquinone (HQ) induce a time-and dose-dependent alteration in the pattern of PU.1-DNA binding in cultured human CD34(+) cells, corresponding to hyperphosphorylation of the PU.1 protein. HQ-induced alterations in PU.1-DNA binding are concomitant with a sustained immature CD34(+) phenotype and cytokine-dependent enhanced clonogenic activity in cultured human HPC. These results suggest that HQ induces a dysregulation in the external signals modulating PU.1 protein phosphorylation and this dysregulation may be an early event in the generation of benzene-induced AML.

Antigens, CD34↗

Hydroquinone modulates the GM-CSF signaling pathway in TF-1 cells.

Human leukemogens, including alkylating chemotherapeutic agents and benzene, enhance granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent proliferation of human CD34+ bone marrow (BM) cells. The extracellular signal-regulated kinase (ERK) pathway plays an important role in GM-CSF-dependent proliferation and also has been implicated in the pathogenesis of acute myelogenous leukemia. Therefore, we investigated the effects of the benzene metabolite, hydroquinone (HQ), on alterations in the GM-CSF signaling pathway in TF-1 erythroleukemia cells and human CD34+ BM cells. HQ treatment in TF-1 cells results in a strong proliferative response that is dependent on ERK activation and GM-CSF production. HQ also induces ERK-dependent AP-1 activation with concomitant increased transcriptional activity of AP-1 reporter gene. However, the kinetics of ERK activation are different between rhGM-CSF and HQ in TF-1 cells: rhGM-CSF results in immediate activation of ERK, whereas HQ activation of ERK is delayed. Further, HQ and rhGM-CSF together produce an immediate increase in ERK phosphorylation, which is sustained for over 48 h. HQ also stimulates colony formation, AP-1 DNA binding and GM-CSF production in human CD34+ BM cells. These results suggest that HQ stimulates proliferation via activation of ERK/AP-1 and is at least partially mediated via the production of GM-CSF.

Antigens, CD34↗

Cyclophosphamide and 5-fluorouracil act synergistically in ovarian clear cell adenocarcinoma cells.

Chemosensitivity to the drugs plays a crucial role in the treatment of ovarian cancer. In this study, we evaluate the cytotoxicity of chemotherapeutic agents in six ovarian cancer cell lines; four clear cell adenocarcinoma and two serous papillary adenocarcinoma, using seven single drugs and seven sets of drug combinations with tetrazolium-based semiautomated colorimetric (MTT) assay. The drug concentration which produced 50% growth inhibition (IC50) of cisplatin was within clinically achievable range in five cell lines. The area under the curve (AUC) at IC50 of cyclophosphamide was below the clinically achievable AUC in two serous papillary cell lines. Paclitaxel was more effective in clear cells than serous papillary cells. The intensification of cytotoxicity was observed in the combinations of paclitaxel and cisplatin, and cyclophosphamide and cisplatin or 5-fluorouracil irrespective of histopathological characteristics of the original tumor. Our results indicate that ovarian cancer cell lines respond to chemotherapeutic agents heterogeneously depending upon histopathological features, indicating individualized regimens may improve survival in ovarian cancer patients.

Adenocarcinoma, Clear Cell↗

Differential roles of spinal neurokinin 1/2 receptors in development of persistent spontaneous nociception and hyperalgesia induced by subcutaneous bee venom injection in the conscious rat.

To evaluate the roles of spinal neurokinin receptors in the development of persistent nociception and hyperalgesia to thermal and mechanical stimuli induced by subcutaneous (s.c.) bee venom injection, effects of intrathecal (i.t.) pre- or post-treatment with a non-selective antagonist of (NK1/2) receptors, [D-Arg1,D-Trp7,9,Leu11] substance P (spantide), and a selective NK3 receptor antagonist, (S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl) piperidin-3-yl)propyl)-4-phenylpiperidin-4-yl)-N-methyl acetamide (SR142801) were assessed in conscious rat. Injection of bee venom s.c. into the plantar surface of one hind paw resulted in a pathological pain phenomenon characterized by a 1-2 h single phase of persistent spontaneous nociceptive behaviors (continuously flinching the injected paw) and a 72-96 h profound primary thermal and mechanical hyperalgesia in the injection site and a secondary thermal hyperalgesia in the non-injected hindpaw. Pre-treatment with spantide i.t. at 0.05 microg, 0.5 microg and 5 microg produced a dose-related suppression of the bee venom-induced flinching reflex during the whole time course and the inhibitory rate was 24 +/- 12.60% (35.38 +/- 4.12 flinches/5 min, n=5), 48 +/- 6.75% (24.53 +/- 2.90 flinches/5 min, n=5) and 60 +/- 7.69% (18.88 +/- 3.58 flinches/5 min, n=5) respectively when compared with the saline control group (46.80 +/- 2.60 flinches/5 min, n=5). Post-treatment of spantide i.t. at the highest dose (5 microg) used in the present study 5 min after bee venom injection also produced a 49% suppression of the flinching reflex in the control group [post-spantide vs saline: 19.42 +/- 3.15 (n=5) vs 38.42 +/- 3.25 flinches/5 min (n=5)]. Moreover, i.t. pre-treatment with 5 microg spantide partially prevented the primary and secondary thermal hyperalgesia from occurring, while it did not show any influence on the development of primary mechanical hyperalgesia. Neither the established thermal nor mechanical hyperalgesia identified in the above sites was affected by i.t. post-treatment with the same dose of spantide 3 h after bee venom injection. Pre and post-treatment of SR142801 did not produce any significant effect on the bee venom-induced spontaneous pain and thermal and mechanical hyperalgesia. Our present result suggests that activation of spinal NK1/2 receptors is involved in both induction and maintenance of the persistent spontaneous nociception, while it is only involved in induction of the primary and secondary thermal, but not primary mechanical hyperalgesia induced by s.c. bee venom injection. The spinal NK3 receptor seems not likely to be involved in the bee venom-induced behavioral response characterized by spontaneous pain and thermal and mechanical hyperalgesia.

Analgesics↗

Time- and concentration-dependent penetration of doxorubicin in prostate tumors.

The penetration of paclitaxel into multilayered solid tumors is time- and concentration-dependent, a result of the drug-induced apoptosis and changes in tissue composition. This study evaluates whether this tissue penetration property applies to other highly protein-bound drugs capable of inducing apoptosis. The penetration of doxorubicin was studied in histocultures of prostate xenograft tumors and tumor specimens obtained from patients who underwent radical prostatectomy. The kinetics of drug uptake and efflux in whole tumor histocultures were studied by analyzing the average tumor drug concentration using high-pressure liquid chromatography. Spatial drug distribution in tumors and the drug concentration gradient across the tumors were studied using fluorescence microscopy. The results indicate that drug penetration was limited to the periphery for 12 hours in patient tumors and to 24 hours in the more densely packed xenograft tumors. Subsequently, the rate of drug penetration to the deeper tumor tissue increased abruptly in tumors treated with higher drug concentrations capable of inducing apoptosis (i.e., = 5 microm), but not in tumors treated with lower concentrations. These findings indicate a time- and concentration-dependent penetration of doxorubicin in solid tumors, similar to that of paclitaxel. We conclude that doxorubicin penetration in solid tumors is time- and concentration-dependent and is enhanced by drug-induced cell death.

Animals↗

[The bridle procedure in treatment of foot deformity in children with slight cerebral spastic paralysis].

OBJECTIVE: To evaluate the effectiveness of the Bridle procedure in treatment of foot deformity in children with slight cerebral spastic paralysis. METHODS: From February 1993 to April 1999, 32 cases with 57 deformed feet, due to slight cerebral spastic paralysis, which included 20 males and 12 females, ranging from 4 to 14 years old, were reported after 6 to 74 months' follow-up, averaging 38 months. Bilateral feet were involved in 25 cases and unilateral feet involved in 7 cases. The deformities in all feet, including 26 feet of acroceph-foot deformity in 15 cases, 13 equinovarus deformity in 8 cases and 18 scissors gait deformity in 9 cases, were treated by Bridle procedure, followed by temporal external fixation of long-leg plaster splint for 6 to 8 weeks. RESULTS: Clinical observation revealed complete and permanent correction of deformity in 48 out of all 57 feet (84.2%), reoccurrence of deformity in 7 feet (12.3%), and occurrence of valgus deformity in 2 feet (3.5%). No joint stiffness was observed. CONCLUSION: The Bridle procedure is an easily performed operation and effective in the treatment of foot deformity in children with slight cerebral spastic paralysis.

Adolescent↗

Quaternary ammonium salt derivative of haloperidol inhibits KCl-induced calcium increase in rat aortic smooth muscle cells.

AIM: To study the effect of quaternary ammonium salt derivative of haloperidol (F3) on intracellular calcium (Ca2+) dynamic change in vascular smooth muscle cells (VSMC). METHODS: Using laser confocal scanning microscopy (LCSM), to observe the effect of F3 (0.01 - 10 micromol/L) on increase of intracellular Ca2+ fluorescent intensity induced by KCl (30 mmol/L) in VSMC. RESULTS: KCl induced a rapid increase of intracellular Ca2+ fluorescent intensity. F3 inhibited the rapid increase of that in both concentration-dependent manner (KCl: 67 +/- 24; F3 0.01 micromol/L: 57 +/- 13; 0.1 micromol/L: 40 +/- 13; 1 micromol/L: 29 +/- 9; 10 micromol/L: 20 +/- 6) and time-dependent manner; during 0 - 30 s after F3 was added, the change of fluorescent intensity was more rapid. CONCLUSION: The inhibitory effect of F3 on Ca2+ concentration in VSMC was mainly due to the blocking of the Ca2+ influx, and might partially attributed to opening of the potassium (K+) channel.

Alkanes↗

[Screening of anti-bacteria activity of extracts of Gaultheria leucocarpa var. yunnanensis].

OBJECTIVE: To further develop Gaultheria leucocarpa var. yunnanensis, anti-bacteria constituents in it were screened. METHOD: The constituents were extracted by chromatographic process. The anti-bacteria test was made with regulatory method of analysis. RESULT AND CONCLUSION: Anti-bacteria test with extracts of water, acetic ester and n-butanol showed that 3 extracts from 22 samples had anti-Staphylococcus aureus action, and the extracts from root and stem showed the same result. 2 extracts could kill Escherichia coli and Pseudomonas aeruginosa. The lower the concentrate, the less the anti-bacteria action was. These results suggested that not only essential oil but other ingredients from G. leucocarpa var.yunnanensis have anti-bacteria activity. Anti-fungi test of the same extracts didn't indicate remarkable action.

Anti-Bacterial Agents↗

[Studies on resources of ethnomedicine Gaultheria leucocarpa var. yunnanensis].

OBJECTIVE: To study the resources of G. leucocarpa var. yunnanensis for further development of this drug. METHOD: Field investigating, consulting with relevant experts and looking into available specimens. RESULTS AND CONCLUSION: G. leucocarpa var. yunnanensis is widely distributed in the southern regions of the Yangtze River. The field investigation suggests that the distribution center is situated in Yunnan province, mainly in Kunming, Chuxiong and Dali counties. The climate in these areas is moderate and moist. G. leucocarpa var. yunnanensis is not a dominant species in this natural environment. In some places, it grows with other species of Gaultheria, such as G. fragrantissima, G. tetramera, G. griffithiana and G. leucocarpa var. cumingiana. It is distributed at altitudes from 400 m to 3,500 m. Accustomed to different sunshine conditions, G. leucocarpa var. yunnanensis prefers stronger sunlight and commonly grows on sunny slopes, seldom in dense forest, propagating itself by roots. As a folk medicine, G. leucocarpa var. yunnanensis is commonly used to treat rheumatic arthritis(RA), dazzling, suppressed menstruation, cold, cough, asthma, strain hematemesis, eczema, ascites, wound, amebic dysentery, acute and chronic prostatitis. It is suggested that further pharmacological and clinical researches of this plant be concentrated on the treatment of RA and relief of aches.

China↗

[Studies on chemical constituents of Gaultheria leucocarpa var. Yunnanensis (Franch.) T. Z. Hsu & R. C. Fang].

OBJECTIVE: To separate and identify the chemical constituents of the aerial part of Gaultheria leucocarpa var. yunnanensis. METHOD: The compounds were extracted with solvents, isolated by column chromatography and identified by spectral analysis. RESULT: Four compounds were identified as n-dotriacontane and its homologous compound(1), ursolic acid(2), vanillic acid(3), and quercitrin(4). CONCLUSION: The compounds 1, 4 were obtained from the plant for the first time, and 2 and 3 were from above-ground part of the plant for the first time.

Alkanes↗

[Non-anthraquinone constituents from Rheum sublanceolatum C. Y. Cheng et Kao].

OBJECTIVE: Study on the non-anthraquinone constituents from rhizoma and radix of Rheum sublanceolatum. METHOD: The constituents were isolated through column chromatography and identified on the basis of their physiochemical and spectral data. RESULT: Six non-anthraquinone constituents were isolated and identified as n-octacosanic acid, sitosterol, daucosterol, 2-methyl-5-carboxymethyl-7-hydroxychromone, piceatannol and 6-hydroxymusizin-8-O-beta-D-glucopyranoside. CONCLUSION: All these compounds were firstly isolated from R. sublanceolatum.

Plant Roots↗

Involvement of spinal protein kinase C in induction and maintenance of both persistent spontaneous flinching reflex and contralateral heat hyperalgesia induced by subcutaneous bee venom in the conscious rat.

To further study the roles of spinal protein kinase C (PKC) in induction and maintenance of both the persistent spontaneous nociception and the contralateral heat hyperalgesia induced by subcutaneous (s.c.) bee venom injection, the effects of intrathecal (i.t.) treatment with a PKC inhibitor, chelerythrine chloride (CH), were evaluated in conscious rats. Pre-treatment i.t. with CH at three doses of 0.01, 0.1 and 1 nmol produced a dose-dependent suppressive effect on the flinching reflex with the inhibitory rates of 39, 48 and 59%, respectively, when compared with the pre-saline control group. Post-treatment i.t. with the drug at the highest dose used (1 nmol) also resulted in a 42% suppression of the flinching reflex compared with the control. Moreover, pre-treatment i.t. with CH at three doses of 0.01, 0.1 and 1 nmol also produced 12, 22 and 48% inhibition of the contralateral heat hyperalgesia in the pre-saline control group. Post-treatment i.t. with the drug at the highest dose used (1 nmol) also resulted in a 35% reversal effect on the established contralateral heat hyperalgesia. The present result suggests that activation of PKC in the spinal cord contributes to the induction and maintenance of both peripherally-dependent persistent spontaneous pain and contralateral heat hyperalgesia which is dependent upon central sensitization.

Animals↗

Modulatory roles of the adenosine triphosphate P2x-purinoceptor in generation of the persistent nociception induced by subcutaneous bee venom injection in the conscious rat.

To study the role of adenosine triphosphate (ATP) P2x-purinoceptor in the persistent nociceptive response induced by subcutaneous (s.c.) bee venom injection, we used a selective P2x receptor antagonist, pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), to evaluate whether spinal P2x receptor play a role in development of spontaneous persistent pain. Injection s.c. of bee venom into the plantar surface of one hindpaw in the conscious rat produces a monophasic, prolonged persistent nociception characterized by continuously flinching reflex of the injected paw for 1-2 h. Intrathecal (i.t.) pretreatment with PPADS at two lower doses of 5 and 10 microg resulted in suppression of the flinching reflex in a dose dependent manner with the inhibitory rate 37 and 44%, respectively, when compared with the control group; whereas i.t. PPADS at a higher dose of 30 microg failed to produce any inhibitory effect. This result suggests that activation of P2x-purinoceptor in the spinal cord contributes to the induction of bee venom-induced prolonged persistent pain. However, the antinociceptive effect of ATP P2x-purinoceptor antagonist such as PPADS on clinical pathological pain seems to be limited due to its lack of effectiveness at higher dose.

Adenosine Triphosphate↗

[Antifungal effect of three natural products on the genetic substance of Saccharomyces cerevisiae GL7 and Prototheca wickerhamii].

AIM: To investigate the antifungal effect of three natural products on the genetic substance of Saccharomyces cerevisiae GL7 and Prototheca wickerhamii. METHODS: The normal and treated cells were observed by confocal laser scanning microscope (CLSM) and image analysis to quantitatively described the cell morphology, area, DNA and RNA content. RESULTS: The morphology, area, DNA and RNA contents were changed greatly in the treated cells. CONCLUSION: Solasodine, 4'-hydroxy-3, 5-dimethoxystilbene and dictamnine directly or indirectly interfered the synthesis and function of genetic substance in S. cerevisiae and P. wickerhamii.

Alkaloids↗

[The structure identification of Julibroside J6 from Albizia julibrissin Durazz].

OBJECTIVE: To study the saponin from Albizia julibrissin. METHODS: A saponin was separated by using chromatography and its structure was elucidated on the basis of spectral data. RESULTS: A saponin was obtained and it's structure was identified as 3-O-[beta-D-xylopyranosyl-(1-->2)-alpha-L-arabinopyranosyl-(1-->6)-beta- D-2-deoxy-2-acetamidoglucopyranosyl]-21-O-(6S-2-trans-2-hydroxymethyl- 6-methyl-6-O-[4-O-(6S-2-trans-2-hydroxymethyl-6-methyl-6-hydroxy-2, 7-octadienoyl)-beta-D-quinovopyranosyl]-2, 7-octadienoyl)-acacic acid-28-O-beta-D-glucopyranosyl(1-->3)-[alpha-L-arabinofuranosyl- (1-->4)]-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl ester. CONCLUSION: The saponin is a new compound named Julibroside J6.

Molecular Structure↗

[Determination of flavonoids in Ginkgo biloba L. leaves from different producing areas].

OBJECTIVE: To compare the contents of flavonoids in the leaves of Ginkgo biloba gathered from 35 producing areas. METHODS: Separating and determining 3 flavonoid aglycones, quercetin, kaempferol and isorhamnetin, by high performance liquid chromatography, and there by calculating the total contents of flavonoids. RESULTS: The contents of flavonoids in the leaves of G. biloba gathered from different producing areas are different, but in those gathered from Pizhou, Zheng'an Xing'an, Anlu, etc. appear higher.

Flavonoids↗

[Studies on chemical constituents of Cistanche tubulosa (Schenk) R. Wight].

OBJECTIVE: To investigate the chemical constituents of Cistanche tubulosa. METHOD: The chemical constituents were isolated by solvent extraction together with various chromatographic techniques including preparative HPLC. The structures were elucidated on the basis of chemical evidence and spectral data. RESULTS: Four iridoid glycosides, one lignan glycoside and one monoterpenoid were isolated from the 95% ethanol extract from the stem of C. tubulosa and identified as adoxosidic acid(I), 8-epiloganic acid(II), geniposidic acid (III), mussaenosidic acid(IV), (+)-syringaresinol-O-beta-D-gluco pyranoside(V) and 8-hydroxygeraniol(VI). CONCLUSION: Compounds I and VI were isolated from the genus of Cistanche for the first time. Compounds III, IV and V were isolated from this plant for the first time.

Carboxylic Acids↗