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Biomedical subjects

Jun Chen

Publications and source records attributed to Jun Chen.

At least 163 records · Page 9Linked to original sources

In vivo studies on toxin accumulation in liver and ultrastructural changes of hepatocytes of the phytoplanktivorous bighead carp i.p.-injected with extracted microcystins.

Phytoplanktivorous bighead carp were injected i.p. with extracted microcystins (mainly MC-RR and -LR) at two doses, 200 and 500 MC-LReq.microg kg(-1) bw, and the changes in extractable MCs in liver and in the ultrastructure of hepatocytes were studied at 1, 3, 12, 24 and 48 h after injection. Quantitative and qualitative determinations of MCs in the liver were conducted by HPLC and LC-MS, respectively. MC concentration in the liver reached the maxima at 12h (2.89 microg MCsg(-1) dry weight at the lower dose) or at 3h (5.43 microg MCsg(-1) dry weight at the higher dose) post-injection, followed by sharp declines afterwards, whereas the ultrastructural changes of hepatocytes in both dose groups suggest progressive increases in severity toward the directions of apoptosis and necrosis from 1 to 24h, respectively. There were two new findings in fish: widening of intercellular spaces was among the early ultrastructural changes induced by MCs and ultrastructural recovery of hepatocytes was evident at 48 h post-injection in both dose groups. Both the present and previous studies suggest that with in vivo or in vitro exposure to microcystins, hepatocyte damage in fish tends to proceed toward the direction of apoptosis at lower MC concentrations but toward the direction of necrosis at high MC concentrations. The temporal dynamics of MCs in the liver suggest that bighead carp may have a mechanism to degrade or bind MC-LR actively after it enters the blood system.

Animals↗

Neuroprotection against focal ischemic brain injury by inhibition of c-Jun N-terminal kinase and attenuation of the mitochondrial apoptosis-signaling pathway.

c-Jun N-terminal kinase (JNK) is an important stress-responsive kinase that is activated by various forms of brain insults. In this study, we have examined the role of JNK activation in neuronal cell death in a murine model of focal ischemia and reperfusion; furthermore, we investigated the mechanism of JNK in apoptosis signaling, focusing on the mitochondrial-signaling pathway. We show here that JNK activity was induced in the brain 0.5 to 24 h after ischemia. Systemic administration of SP600125, a small molecule JNK-specific inhibitor, diminished JNK activity after ischemia and dose-dependently reduced infarct volume. c-Jun N-terminal kinase inhibition also attenuated ischemia-induced expression of Bim, Hrk/DP5, and Fas, but not the expression of Bcl-2 or FasL. In strong support of a role for JNK in promoting the mitochondrial apoptosis-signaling pathway, JNK inhibition prevented ischemia-induced mitochondrial translocation of Bax and Bim, release of cytochrome c and Smac, and activation of caspase-9 and caspase-3. The potential mechanism by which JNK promoted Bax translocation after ischemia was further studied using coimmunoprecipitation, and the results revealed that JNK activation caused serine phosphorylation of 14-3-3, a cytoplasmic sequestration protein of Bax, leading to Bax disassociation from 14-3-3 and subsequent translocation to mitochondria. These results confirm the role of JNK as a critical cell death mediator in ischemic brain injury, and suggest that one of the mechanisms by which JNK triggers the mitochondrial apoptosis-signaling pathway is via promoting Bax and Bim translocation.

14-3-3 Proteins↗

Evaluation of the bioequivalence and pharmacokinetics of two formulations of rizatriptan after single oral administration in healthy volunteers.

The pharmacokinetic parameters of two oral formulations of rizatriptan (CAS 144034-80-0, a capsule preparation as test and rizatriptan tablet as reference), given at a single dose of 10 mg each, were compared in an open-label, randomized, single oral dose, two-period cross-over design in 20 healthy volunteers under fasting conditions. Plasma concentrations of rizatriptan were measured by a validated HPLC assay. The parametric 90% confidence intervals of the geometric mean values of the test/reference ratios were 91.9% to 101.9% (point estimate: 97.3%) for AUC(0-infinity), 93.0% to 102.2% (point estimate: 96.5%) for AUC(0-t), 90.1% to 100.0% (point estimate: 95.4%) for Cmax, being within the acceptance criteria for bioequivalence (80%-125%). Tmax values were analyzed by the nonparametric Wilcoxon test and the difference was not statistically significant. Therefore, it is concluded that the test and reference rizatriptan formulations are bioequivalent with regard to both the extent and the rate of absorption.

Adult↗

The immunomodulator vasoactive intestinal peptide (VIP) does not affect experimental autoimmune uveitis (EAU) in B10.RIII mice.

PURPOSE: Vasoactive intestinal peptide (VIP) exhibits immunomodulatory activities both in vivo and in vitro, including efficient inhibition of murine experimental arthritis. In this study, we investigated the effects of VIP treatment on the induction of experimental autoimmune uveoretinitis (EAU). METHODS: EAU was induced in B10.RIII mice by immunization with interphotoreceptor retinoid-binding protein (IRBP) using routine methods, but without treatment with pertussis toxin (PTX). VIP was injected i.p. at different doses into mice on alternate days. Mice were tested by conventional methods for ocular inflammation, antibody levels, lymphocyte proliferation, and cytokine release by cultured lymphocytes. RESULTS: Treatment with VIP, at different doses, had essentially no effect on the development of EAU or antibody production in the B10.RIII mice. The treatment did have variable effects on the low interferon-gamma production by lymphocytes of these mice. CONCLUSION: Unlike its inhibitory effect in the experimental arthritis system, VIP did not modulate the development of EAU in B10.RIII mice.

Animals↗

Overexpression of inducible nitric oxide synthase in the kidney of the spontaneously hypertensive rat.

In kidney, nitric oxide (NO) produced by nitric oxide synthase (NOS) regulates sodium and water excretion and renal medullary blood flow. However, excessive NO production causes nitrative damage and oxidative stress. Since oxidative stress may be linked to hypertension, we examined the expression and activity of inducible NOS (iNOS) in the kidney of the spontaneously hypertensive rat (SHR) and compared our findings to control normtotensive Wistar Kyoto (WKY) rat. Compared with WKY rat, there was significant (p < .05) overexpression (by 96%) and increased (2-fold) activity of iNOS in the cortex but not in the outer medulla, of SHR kidney; in the inner medulla, there was a 6.9-fold increase in iNOS activity in SHR. Increased expression (by 104%) and activity (3.3-fold) of iNOS was specifically observed in proximal tubules (PTs) of the cortex, accompanied by higher (2-fold) tissue nitrite levels. Although certain antioxidant enzymes such as catalase and Mn-superoxide dismutase were overexpressed, glutathione peroxidase was underexpressed in SHR PTs. Overexpression of the inducer of the iNOS promoter, nuclear factor-kappaB (NF-kappaB), with elevated nitrotyrosinylated proteins, further confirmed an elevated state of iNOS-induced oxidative stress in SHR kidneys, possibly signifying its role in the maintenance of essential hypertension seen in these animals.

Animals↗

Apoptosis inducing factor mediates caspase-independent 1-methyl-4-phenylpyridinium toxicity in dopaminergic cells.

Parkinson's disease is a debilitating neurodegenerative disease characterized by loss of midbrain dopaminergic neurons. These neurons are particularly sensitive to the neurotoxin 1-methyl-4-phenylpyridinium (MPP+), the active metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which causes parkinsonian syndromes in humans, monkeys and rodents. Although apoptotic cell death has been implicated in MPTP/MPP+ toxicity, several recent studies have challenged the role of caspase-dependent apoptosis in dopaminergic neurons. Using the midbrain-derived MN9D dopaminergic cell line, we found that MPP+ treatment resulted in an active form of cell death that could not be prevented by caspase inhibitors or over-expression of a dominant negative inhibitor of apoptotic protease activating factor 1/caspase-9. Apoptosis inducing factor (AIF) is a mitochondrial protein that may mediate caspase-independent forms of regulated cell death following its translocation to the nucleus. We found that MPP+ treatment elicited nuclear translocation of AIF accompanied by large-scale DNA fragmentation. To establish the role of AIF in MPP+ toxicity, we constructed a DNA vector encoding a short hairpin sequence targeted against AIF. Reduction of AIF expression by RNA interference inhibited large-scale DNA fragmentation and conferred significant protection against MPP+ toxicity. Studies of primary mouse midbrain cultures further supported a role for AIF in caspase-independent cell death in MPP+-treated dopaminergic neurons.

1-Methyl-4-phenylpyridinium↗

Endothelial cell dysfunction: the syndrome in making.

Endothelial cell dysfunction is emerging as the ultimate culprit for diverse cardiovascular diseases and cardiovascular complications in patients with chronic renal diseases, yet the definition of this new syndrome, its pathophysiology and therapy remain poorly defined. Here, we summarize some molecular mechanisms leading from hyperhomocysteinemia, elevated asymmetric dimethylarginine (ADMA) and advanced glycation end products (AGEs)-modified proteins to atherogenic endothelial phenotype and offer a model of endothelial dysfunction based on the interconnectedness of diverse functions.

Animals↗

Effects of complete Freund's adjuvant on immunohistochemical distribution of IL-1beta and IL-1R I in neurons and glia cells of dorsal root ganglion.

AIM: To investigate the effects of complete Freund adjuvant (CFA) on inflammatory hyperalgesia and morphological change of the coexistence of interleukin-1 beta (IL-1beta) and type I IL-1 receptor (IL-1RI) in neurons and glia cells of rat dorsal root ganglion (DRG). METHODS: The pain-related parameters and the expression of IL-1RI and IL-1beta positive neurons and glia cells of DRG in normal saline (NS) and adjuvant-induced arthritic (AA) group were examined with pain behavior assessment methods and immunohistochemical assay, respectively. RESULTS: Five hours, 1 d, and 2 d after intra-articular injection of 50 microL CFA, tactile hyperalgesia induced by CFA was observed in the foot flexion and extension scores of the ipsilateral hindpaw of AA group. Three days after injection, the distribution of IL-1RI/IL-1beta double-stained coexisted neurons and glia cells were observed in ipsilateral DRG of both groups. The number of IL-1beta positive neurons, IL-1RI positive neurons, IL-1beta/IL-1RI double-stained neurons, and IL-1RI positive glia cells in ipsilateral DRG of the AA group were higher than that of NS group (P<0.05 or P<0.01). CONCLUSION: The coexistence of IL-1beta and IL-1RI in neurons and nonneuronal cells suggests an as yet unknown autocrine and/or paracrine function of IL-1beta in the DRG. The function was enhanced in articular arthritis induced by CFA and could play an important role in hyperalgesia under inflammatory conditions.

Animals↗

Sapphyrins induce apoptosis in hematopoietic tumor-derived cell lines and show in vivo antitumor activity.

Sapphyrins are pentapyrrolic, metal-free, expanded porphyrins. In the present study, the activity of sapphyrins as anticancer agents in hematopoietic-derived tumor cells was explored. It was found that a dihydroxylated water-soluble sapphyrin derivative (PCI-2000) is a potent inducer of apoptosis in a wide variety of tumor cell lines including lymphoma (Ramos, DHL-4, and HF-1), leukemia (Jurkat and HL-60), and myeloma (8226/S, 1-310, C2E3, and 1-414). PCI-2000 triggers an apoptotic pathway in these tumor cells as shown by release of cytochrome c from mitochondria; activation of caspases 9, 8, and 3; cleavage of the caspase substrate poly(ADP-ribose) polymerase; and Annexin V binding. Apoptosis can be partially inhibited by overexpression of the antiapoptotic protein Bcl-2 or treatment with benzyloxycarbonyl-valine-alanine-aspartic acid-fluoromethylketone, a cell-permeable caspase inhibitor. Both PCI-2000 and PCI-2010, a tetrahydroxy bis-carbamate derivative of PCI-2000, result in increased levels of phosphorylated p38 mitogen-activated protein kinase. Inhibition of p38 mitogen-activated protein kinase phosphorylation resulted in a synergistic increase of PCI-2000 cytotoxicity. PCI-2010 showed less toxicity in mice than PCI-2000 and was active in slowing the growth of Ramos and HL-60 tumor xenografts in nude mice. These results provide preclinical rationale for the further study of sapphyrins for potential use in the treatment of hematopoietic-derived tumors.

Angiogenesis Inhibitors↗

Coupling of conjugating enzymes and efflux transporters: impact on bioavailability and drug interactions.

Abstract: Conjugating enzymes are traditionally recognized as one of the major biological barriers to the entry of xenobiotics/drugs into systemic circulation and represent one of the main pathways for their elimination. Similar to drugs that undergo extensive phase I metabolism, drugs that undergo extensive conjugation have poor bioavailability and are more prone to metabolism-based drug interactions. Previously, enterohepatic recycling is used to explain why certain xenobiotics have half-lives that are much longer than expected from intravenous injection studies. In addition, changes in expression levels of metabolic enzymes due to chemical induction or suppression are often recognized as the source of drug interaction or toxicity of pollutants and carcinogens. These traditional approaches, whereas yielding highly valuable information, fail to recognize the fact that many conjugates (especially hydrophilic ones) cannot permeate the cell membrane. In the present review, we will focus on the coupling process that involves both conjugating enzymes and efflux transporters. We will briefly review conjugating enzymes capable of producing highly hydrophilic metabolic products. The other focus of this review is on various transporters capable of moving negatively charged hydrophilic conjugates across the cellular membrane. Evidence will support the hypothesis that efficient coupling of the conjugating enzymes and efflux transporters enables enterohepatic recycling and enteric recycling processes. Termed as a "revolving door" theory, the hypothesis focuses on the role played by efflux transporter capable of modulating the cellular excretion of hydrophilic metabolites. Coupling process in intestine, liver and kidney will be discussed with an emphasis on the intestinal coupling process, since we have just begun to understand it. Biological consequence and new insights into how coupling process can impact bioavailability of xenobiotics, biological functions of drugs and carcinogens, and drug interactions will be discussed.

Biological Availability↗

[Expression of the kallikreins-kinins system in the corpus cavernosum of rats].

OBJECTIVE: To study the expression of the kallikreins-kinins system in the corpus cavernosum of rats. METHODS: The expression of tissue kallikrein I and kinin B2 receptor gene in the corpus cavernosum and heart of adult rats was detected by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The tissue kallikrein I and kinin B2 receptor were detected in the corpus cavernosum as well as in the heart of the rats and the contents were similar. CONCLUSION: A kallikreins-kinins system exists in the corpus cavernosum of rats, and the content is rich, almost similar to that in the heart.

Animals↗

[Correlation between magnetic resonance diffusion weighted imaging and cell density in astrocytoma].

OBJECTIVE: To evaluate the apparent diffusion coefficients (ADC) in magnetic resonance diffusion weighted imaging with echo-planar technique in depicting the tumor cellularity and grading of astrocytoma. METHODS: Thirty-four astrocytoma patients including 18 male and 16 female with age from 10 to 73 years (mean 38.4 years) were examined by MRI and eventually proved by surgical resection and pathological examination. Of them, 26 had low-grade (grade I, II) astrocytoma and 8 high-grade (grade III, IV) astrocytoma. ADC value of astrocytoma was determined on magnetic resonance diffusion weighted images. Cellularity of the astrocytoma was analyzed using Adobe Photoshop 7.0.1 software. RESULTS: The mean ADC value (in units of 10(-4) mm(2)/s) of the high-grade astrocytomas (7.34 +/- 2.95) was significantly lower than that of the low-grade astrocytomas (13.76 +/- 3.31) (t = 4.91, P < 0.001). The mean cellularity of the high-grade astrocytomas (19.81 +/- 9.73)% was significantly higher than that of the low-grade astrocytomas (4.74 +/- 2.96)% (t = 4.32, P = 0.003). ADC value of the astrocytoma was significantly and negatively correlated with its cellularity (r = -0.535, P = 0.001). CONCLUSION: ADC value of astrocytoma is significantly and negatively correlated with its cellularity. Magnetic resonance diffusion weighted imaging may well be highly potential in predicting the degree of astrocytoma.

Adolescent↗

[Study on yield and quality of Scutellaria baicalensis from different habitats].

OBJECTIVE: To compare the economical characters, yield characters and major effective ingredient content of Scutellaria baicalensis from different habitats. METHOD: The characters were studied by field randomized block test combining analysis of variance, correlation analysis and quality analysis. RESULT: There are significant differences in yield and quality of the crude drugs from different habitats. CONCLUSION: The crude drug from Pingyi (Shandong province) is better than those from other habitats.

Biomass↗

Physicochemical basis for binding and voltage-dependent block of hERG channels by structurally diverse drugs.

Blockade of hERG K+ channels in the heart is an unintentional side effect of many drugs and can induce cardiac arrhythmia and sudden death. For this reason, most pharmaceutical companies screen compounds for hERG channel activity early in the drug discovery/development process. A detailed understanding of the drug binding site(s) on the hERG channel could enable rational design of future medications devoid of this unwanted side effect. Towards this goal, we have used site-directed mutagenesis to identify several residues of the hERG channel that comprise a common drug binding site. The initial Ala-scan identified several residues located in the S6 domain (Tyr652, Phe656) and the base of the pore helix (Thr623, Ser624, Val625) as important sites of interaction. Here, we review studies that refine our understanding of the physicochemical basis of interaction by structurally diverse drugs with aromatic residues in the S6 domain. Our findings suggest that the position of Tyr652 and Phe656 in hERG is optimal for interaction with multiple drugs, Tyr652 is an important determinant of voltage-dependent block, and the hydrophobic surface area of residue 656 and aromaticity of residue 652 are the physicochemical features required for high-affinity block by MK-499, cisapride and terfenadine.

Action Potentials↗

[Determination of 1-deoxynojirimycin in leaves of Morus alba by high performance liquid chromatography with fluorescence detection].

OBJECTIVE: To develop a high performance liquid chromatographic method for the determination of DNJ in Morus alba leaves with fluorimetric detection after precolumn derivatization with 9-fluorenylmnethyl chlorformate (FMOC-Cl). METHOD: DNJ in Morus alba leaves was extracted with 0.05 mol x L(-1) HCl, reacted with FMOC-Cl, and separated on a HiQSiL C18 column at 250 degrees C. Mobile phase consisted of acetonitrile-0.1% aqueous acetic acid (55:45) with a flow rate of 1.0 mL x min. The fluorescence detector was operated at lambdaEX = 254 nm, lambdaEM = 322 nm. RESULT: A satisfactory separation between DNJ and impurity was obtained. The calibration curve was linear over the concentration range from 0.567 microg x mL(-1) to 34 microg mL(-1), r = 0.9998. The average recovery was 97.2%. The contents of DNJ in M. alba collected in different seasons and grown in different environment were determined. CONCLUSION: The quantity of DNJ in leaves of M. alba is related to the environment factor, temperature and growing period. The method can be used for qualioy control of the medicinal material.

1-Deoxynojirimycin↗

Pilot regulation of MnP-SA for treating PTA wastewater.

In the pilot study of treating the purified terephthalic acid (PTA) wastewater with the functional Strain Fhhh in the carrier activated sludge process (CASP), the ratio of COD: TN: TP and the concentrations of Cu, Mn, Se and Zn were controlled to improve the manganese peroxidase (MnP) levels for increasing the treatment efficiency. When the ratio of COD: TN: TP was 100: 0.36: 0.15 and the concentrations of Cu, Mn, Se and Zn were 0.54, 5.07, 0.00 and 0.08 mg/L, the MnP specific activity (MnP-SA) reached 689 U/L, and the sludge loading rate to COD(SLRC) was 1.09 d(-l), which was 4--7 fold of that in other processes reported. The data indicated that improving MnP level could enhance the degradability of Fhhh. And the potentials of Fhhh and CASP will be also discussed in this paper.

Bacteria↗

[Determination of constant and trace elements in Ranunculus ternatus thunb by ICP-AES].

The determination of twenty one kinds of constant and trace elements in Chinese herb Ranunculus ternatus thunb was performed by ICP-AES. The results show that K, Fe, Ca, Cr, Mg, Mn, Zn, Co, Cu, Ni, Se and Sr are relatively rich in Ranunculus ternatus and the content of Pb, Cd and As are very low. The ratio of the content of Zn to that of Cu is about 3, which is consistent with the relative content level of Zn and Cu contained in many anticancer Chinese traditional plants.

Antineoplastic Agents↗