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Biomedical subjects

K Wen

Publications and source records attributed to K Wen.

11 recordsLinked to original sources

Expression of elevated levels of pro-inflammatory cytokines in SARS-CoV-infected ACE2+ cells in SARS patients: relation to the acute lung injury and pathogenesis of SARS.

The authors have previously shown that acute lung injury (ALI) produces a wide spectrum of pathological processes in patients who die of severe acute respiratory syndrome (SARS) and that the SARS coronavirus (SARS-CoV) nucleoprotein is detectable in the lungs, and other organs and tissues, in these patients. In the present study, immunohistochemistry (IHC) and in situ hybridization (ISH) assays were used to analyse the expression of angiotensin-converting enzyme 2 (ACE2), SARS-CoV spike (S) protein, and some pro-inflammatory cytokines (PICs) including MCP-1, TGF-beta1, TNF-alpha, IL-1beta, and IL-6 in autopsy tissues from four patients who died of SARS. SARS-CoV S protein and its RNA were only detected in ACE2+ cells in the lungs and other organs, indicating that ACE2-expressing cells are the primary targets for SARS-CoV infection in vivo in humans. High levels of PICs were expressed in the SARS-CoV-infected ACE2+ cells, but not in the uninfected cells. These results suggest that cells infected by SARS-CoV produce elevated levels of PICs which may cause immuno-mediated damage to the lungs and other organs, resulting in ALI and, subsequently, multi-organ dysfunction. Therefore application of PIC antagonists may reduce the severity and mortality of SARS.

Acute Disease↗

An antagonist of retinoic acid receptors more effectively inhibits growth of human prostate cancer cells than normal prostate epithelium.

Screening of synthetic retinoids for activity against prostate carcinoma cell lines has identified antagonists of retinoic acid receptors (RARs) as potent growth inhibitors (Hammond et al, 2001, Br J Cancer 85, 453-462). Here we report that 5 days of exposure to a high-affinity pan-RAR antagonist (AGN194310) abolished growth of prostate carcinoma cells from 14 out of 14 patients, with half-maximal inhibition between 200 and 800 nM. It had similar effects (at approximately 250 nM) on the prostate carcinoma lines LNCaP, DU-145 and PC-3. AGN194310 inhibited the growth of normal prostate epithelium cells less potently, by 50% at approximately 1 microM. The growth of tumour cells was also inhibited more than that of normal cells when RARbeta together with RARgamma, but not RARalpha alone, were antagonised. Treatment of LNCaP cells with AGN194310 arrested them in G1 of cell cycle within 12 h, with an accompanying rise in the level of p21(waf1). The cells underwent apoptosis within 3 days, as indicated by mitochondrial depolarisation, Annexin V binding and DNA fragmentation. Apoptosis was caspase-independent: caspases were neither cleaved nor activated, and DNA fragmentation was unaffected by the pan-caspase inhibitor Z-VAD-FMK. The ability of AGN 194310 to induce apoptosis of prostate cancer cells and its differential effect on malignant and normal prostate epithelial cells suggests that this compound may be useful in the treatment of prostate cancer.

Apoptosis↗

Substrate-induced modulation of the Raman scattering signals from self-assembled organic nanometric films.

Raman scattering signals recorded by microscopy from organic self-assembled monolayers (thin nanometric films of calibrated thickness) on silica substrates were found to be much stronger than those obtained from identical films assembled on bulk silicon substrates. This effect, observed in the backscattering geometry, is shown to result from interferences between the direct and reflected beams (including both the excitation and scattered radiation) in front of a smooth reflecting surface. Strong dependence of the effect on the distance between the sampled monolayer and the bulk silicon substrate allows enhancement of the Raman signals of organic monolayer films on silicon by factors up to approximately 70 by using appropriate silica spacers. The dependence of the Raman signal intensity on film thickness was also studied for thicker nanometric films comprising a series of self-assembled organosilane multilayers on bulk silicon and fused silica substrates, and the predicted deviation from linearity in the case of the silicon substrate is experimentally confirmed.

Journal Article↗

The synthesis of beta-peptides containing guanidino groups.

The synthesis of the beta-peptide 1 by the postsynthetic modification of the corresponding amino-containing peptide 3 is described. The potential of 1 to act as a template for the ligation of complementary negatively-charged peptides is discussed.

Amino Acids↗

[Expression of bcl-2 and p16 in transitional cell carcinoma of urinary bladder].

OBJECTIVE: To study the relationship between the expression of proto-oncogene bcl-2 and MTS1/p16 in transitional cell carcinoma of bladder and prognosis. METHODS: Immunohistochemical SABC method was used to detect the expression of proto-oncogene bcl-2 and MTS1/p16 in 51 paraffin-embedded primary transitional cell carcinoma of bladder specimens and 5 normal bladder mucosa specimens. RESULTS: The positive expression of bcl-2 was seen in 80.2% (42/51) tumors. There was statistically significant correlation between prognosis and the positive expression of bcl-2. The positive expression rate was higher in tumors with poorer prognosis than in those with better prognosis (P < 0.05). The expression of p16 protein was positive in 50.9% (26 of 51) in tumors and negative in all 5 normal bladder mucosae. The positive expression rate of p16 descended with increasing grade, stage and poorer prognosis. Clinicopathological characteristics and prognosis were related to the expression of p16 (P < 0.05). The positive expression of bcl-2 versus negative expression of p16 were seen in 20 of 51 of tumors, with distributing grade I 3/11, grade II 9/26, grade III 8/14, Tis - T(1) 6/28, T(2) 10/17, T(3) 4/6, A group 5/20, B group 4/16, and C group 11/15, respectively. Both bcl-2 and p16 were positively expressed in 22 of 51 of tumors. Their positive expressions were higher in tumors with lower grade, stage and better prognosis than in those with worse clinicopathological characteristics and poorer prognosis (P < 0.05). CONCLUSIONS: Over-expression of bcl-2 appears to be common in bladder cancer; over-expression of proto-oncogene bcl-2 and inactivation of the MTS1/p16 gene are likely to be contributing factors for primary bladder cancer; and they can be the prognostic indicators for transitional cell carcinoma of urinary bladder.

Adult↗

Candida albicans triggers interleukin-6 and interleukin-8 responses by oral fibroblasts in vitro.

Oral candidiasis is the most frequent opportunistic infection associated with an immunocompromised host. Production of proinflammatory cytokines, such as interleukin-6 (IL-6) and IL-8, by host cells in response to Candida albicans can be expected to have a major impact in the activation of immune effector cells against the invading microorganism. Using a human cell--C. albicans coculture model system, we determined that this microorganism can trigger secretion of these potent chemoattractant and proinflammatory cytokines by oral mucosal fibroblasts. This response varied depending on the infecting strain and required fungal viability, germination of yeast into hyphae and mannose-mediated direct contact between the host cell and Candida. The secretion of proinflammatory cytokines by oral mucosal fibroblasts in response to C. albicans suggests that these cells have the potential to enhance the host defense against this organism in vivo. This may have important implications in controlling fungal overgrowth in the oral cavity.

Candida albicans↗

Methimazole and propylthiouracil increase cellular thyroid peroxidase activity and thyroid peroxidase mRNA in cultured porcine thyroid follicles.

Methimazole (MMI) and propylthiouracil (PTU) are common antithyroid drugs for treating hyperthyroidism because the 2 drugs inhibit thyroid peroxidase (TPO)-catalyzed thyroid hormone formation. We studied whether the 2 drugs actually inhibit cellular TPO activity in cultured porcine follicles. Porcine follicles were cultured in the presence of 1 mU/mL thyrotropin (TSH) for 7 days. Then follicles were exposed to MMI or PTU in the presence of 0.1 microM Kl for 2 days. TPO activity was measured in the 100,000 x g-pellet of the thyroid sonicate by the guaiacol oxidation method. Exposure to MMI (1 microM and 10 microM) or PTU (10 microM and 100 microM) for 2 days caused a significant increase in cellular TPO activity; 100 microM MMI inhibited cellular TPO activity. The presence of cyclic adenosine monophosphate (cAMP)-generating system (forskolin) in TSH-free medium increased MMI-mediated TPO activity. Cyclohexamide inhibited MMI-mediated TPO activation, indicating that new protein synthesis is required for increased TPO activity. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed an increase in TPO mRNA by PTU or MMI. In conclusion, MMI and PTU at therapeutic concentrations can increase TPO mRNA and cellular TPO activity, although the 2 drugs inhibit the TPO-H2O2-mediated catalytic reaction.

Animals↗

[Experimental research on laser-induced single-molecule detection].

Single-molecule detection is a kind of ultra-high sensitive detection technique. It is widely used in biology, medicine, environment and so on. Here we report briefly the principle and device of our laser-induced single-molecule detection spectrum instrument. We also report the experimental results on the instrument by using C445 dye, including the affection of sample velocity, energy characteristic, consistence linearity and detection limit. We discuss the effect of photon bleach on experimental results. These results are the base of our future work.

Chemistry Techniques, Analytical↗

[Ultrasensitive analysis of R6G and R110 in solution].

This paper describes the ultrasensitive detection of R6G and R110 in a flowing aqueous sample, based on laser-induced fluorescence (LIF) combined with mode-locked pulsed excitation and time-correlated single-photon counting. A high repetition rate mode-locked argon ion laser operated at 514.5 nm was used as the excitation source. The laser beam was found tightly into a thin wall capillary flow cell. The probe volume was about 12.6 x 10(-12)L. Fluorescence was collected at 90 degrees using a x 40 microscope objective, and was detected by a fast response PMT detector. A time-gate was used to discriminate Raman scattering light background. Using the criterion of 3 standard deviations above background, the detection limits obtained for R6G and R110 were 3.8 x 10(-14) mol/L and 1 x 10(-13) mol/L respectively, and the average probability was lower than 1 in the presence of a R6G or a R110 molecule in the detection volume.

Lasers↗

[Analysis of trace Pd in marine deposit samples using laser-excited atomic fluorescence spectrometry].

Laser-excited atomic fluorescence spectrometry and its experimental set-up are introduced in this paper. Using this spectrometer, Pd contents in 36 marine deposit samples of the East-sea continental shelf were analyzed. The results show that the detection limit and the precision of this spectrometer are 50 pg/mL and 6% respectively, and the measurements of Pd in marine deposit samples are reliable.

English Abstract↗

[Development of a SIRI-TOFMS and the application research progress].

The only one set of Sputter Initiated Resonance Ionization-Time of Flight Mass Spectrometer (SIRI-TOFMS) in China was designed and developed. A liquid gallium ion source with micron level diameter of beam, frame-style piezoeletric ceramic sub-micron sample manipulator, a secondary electron imaging system and a computer controlled precise targeting system as well as a real colour big screen image displaying system were added so as to improve its microanalysis capability. By means of this apparatus, trace analysis of Au in minerals and Cu in standard steel samples were carried out. The detection limit of them is 40ng/ and microg/g level, respectively. Aside from the above detections, other preliminary researches ere also performed.

English Abstract↗