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Biomedical subjects

Jun Yan

Publications and source records attributed to Jun Yan.

At least 55 records · Page 3Linked to original sources

SRC-3 is required for prostate cancer cell proliferation and survival.

Prostate cancer is the most common cancer in men in America. Currently, steroid receptor coactivators have been proposed to mediate the development and progression of prostate cancer, at times in a steroid-independent manner. Steroid receptor coactivator-3 (SRC-3, p/CIP, AIB1, ACTR, RAC3, and TRAM-1) is a member of the p160 family of coactivators for nuclear hormone receptors including the androgen receptor. SRC-3 is frequently amplified or overexpressed in a number of cancers. However, the role of SRC-3 in cancer cell proliferation and survival is still poorly understood. In this study, we show that SRC-3 is overexpressed in prostate cancer patients and its overexpression correlates with prostate cancer proliferation and is inversely correlated with apoptosis. Consistent with patient data, we have observed that reduction of SRC-3 expression by small interfering RNA decreases proliferation, delays the G1-S transition, and increases cell apoptosis of different prostate cancer cell lines. Furthermore, with decreased SRC-3 expression, proliferating cell nuclear antigen and Bcl-2 expression, as well as bromodeoxyuridine incorporation in prostate cancer cells are reduced. Finally, knockdown of SRC-3 with inducible short hairpin RNA expression in prostate cancer cells decreased tumor growth in nude mice. Taken together, these findings indicate that SRC-3 is an important regulator of prostate cancer proliferation and survival.

Acetyltransferases↗

[The antitumor activity of Shuang-Xi-Zuo-Wan-1 in C57/BL mice].

OBJECTIVE: To detect the antitumor activity of Shuang-Xi-Zuo-Wan-1(Eb), a novel organoselenium compound, in C57/BL mice transplanted with Lewis lung cancer(LLC). METHODS: The LLC transplanted C57/BL mice model was established,and the mice were randomly divided into four groups, including high dose Eb group (25.0 mg/kg), low dose Eb group (12.5 mg/kg), positive control group (DDP, 2.0 mg/kg) and negative control group (solvent). Each group had twelve mice. Intraperitoneal injections (ip.) of four pharmaceuticals were performed once a day through the abdominal wall separately, from the second to the eighth days after cancer was transplanted. On the eleventh day, six mice of each group were killed and the influences of Eb on growth speed, size, weight, invasion, inhibitory rate, proliferation index and apoptosis rate of LLC were observed and calculated. The remaining mice were fed till all of them died naturally and the average survival time of each group was calculated. RESULTS: Eb could inhibit the growth and infiltration of LLC (the cancer inhibitory rate of high does Eb was 80.31%) obviously and prolong the average survival time of these with mice cancer. After being given Eb, the nuclear of the cancer cell concentrated and the fission phase cells reduced. In addition,the number of apoptosis cancer cells increased. CONCLUSION: The novel organoselenium compound Eb has antitumor activity in vivo. It can inhibit the growth and infiltration of LLC in mice, and induce the apoptosis of cancer cells.

Animals↗

A thioredoxin reductase inhibitor induces growth inhibition and apoptosis in five cultured human carcinoma cell lines.

Human thioredoxin reductase (TrxR) system is associated with cancer cell growth and anti-apoptosis process. Effects of 1, 2-[bis (1,2-Benzisoselenazolone-3 (2H) -ketone)]ethane (BBSKE), a novel TrxR inhibitor, were investigated on A549, HeLa, Bel-7402, BGC823 and KB cell lines. After treated with BBSKE, a good linear correlation coefficient (r>or=0.989) between TrxR activity and cell viability exists in each cell line together with cell growth/proliferation inhibition and apoptosis through Bcl-2/Bax and Caspase-3 pathways. These results suggest that there exists some relationship between TrxR inactivation and growth/proliferation inhibition or apoptosis in the investigated cell lines.

Antineoplastic Agents↗

Targeting antigen to CD19 on B cells efficiently activates T cells.

CD19 is a B cell-surface molecule that participates as an important regulatory signaling complex for antigen bound at the surface by Ig. Triggering of CD19 through its linkage with CD21 amplifies signals transduced through the Src family kinases and modulates B cell differentiation in response to antigen. This study examines the kinetics of antigen uptake and processing of antigen directly targeted to the CD19 protein on purified B cells. We have demonstrated that the antigen internalized within minutes through CD19 forms a cap at the B cell surface and can be found within lysosomes in the cytoplasm in 90 min. B cells acquiring antigen via CD19 express elevated levels of B7-1 and B7-2 co-stimulatory molecules. Moreover, antigen-anti-CD19 complexes administered intravenously bind B cells in vivo and activate antigen-specific T cells more efficiently than non-specific uptake and in a manner similar to antigen taken up through surface IgM on B cells. This work illustrates an important and previously unrecognized mechanism for targeting proteins to B lymphocytes for antigen presentation and activation of CD4 T cells.

Animals↗

C5a-mediated leukotriene B4-amplified neutrophil chemotaxis is essential in tumor immunotherapy facilitated by anti-tumor monoclonal antibody and beta-glucan.

Intravenous and orally administered beta-glucans promote tumor regression and survival by priming granulocyte and macrophage C receptor 3 (CR3, iC3bR and CD11b/CD18) to trigger the cytotoxicity of tumor cells opsonized with iC3b via anti-tumor Abs. Despite evidence for priming of macrophage CR3 by oral beta-glucan in vivo, the current study in C57BL/6 and BALB/c mice showed that granulocytes were the essential killer cells in mAb- and oral beta-glucan-mediated tumor regression, because responses were absent in granulocyte-depleted mice. Among granulocytes, neutrophils were the major effector cells, because tumor regression did not occur when C5a-dependent chemotaxis was blocked with a C5aR antagonist, whereas tumor regression was normal in C3aR(-/-) mice. Neutrophil recruitment by C5a in vivo required amplification via leukotriene B(4), because both C5a-mediated leukocyte recruitment into the peritoneal cavity and tumor regression were suppressed in leukotriene B(4)R-deficient (BLT-1(-/-)) mice.

Administration, Oral↗

Atrial natriuretic peptide induces an acrosome reaction in giant panda spermatozoa and enhances their penetration of salt-stored porcine oocytes.

Atrial natriuretic peptide (ANP) is a vasodilator peptide primarily produced in the heart. Locally synthesized ANP has been found in reproductive tissues of various mammals and humans, and plays an important role in rat oocyte maturation and human sperm function. The objective of the present study was to determine the effects of ANP on the function (acrosome reaction and zona penetration) of giant panda spermatozoa. In fresh and frozen-thawed spermatozoa that had been preincubated for 2.5h, treatment with ANP (for 60 min) significantly increased the proportion of acrosome-reacted spermatozoa; maximal response (an acrosome reaction in 18.3 and 21.8% of fresh and frozen-thawed spermatozoa, respectively) was detected at 1 nM ANP. Treatment with C-ANP-(4-23), an analogue of ANP and specific binder to natriuretic peptide receptors-C (NPRC), had no significant effect on the acrosome reaction. However, the cyclic guanosine 5'-monophosphate (cGMP)-dependent protein kinase (PKG) inhibitor KT5823 completely abolished the effect of ANP on acrosome reaction. The effects of ANP, caffeine and heparin on frozen-thawed sperm function were studied by insemination of porcine salt-stored oocytes in a modified Tris-buffered medium (mTBM). The presence of ANP, caffeine or heparin in the insemination medium resulted in a higher proportion (P < 0.05) of oocytes with spermatozoa in the zona and perivitelline space (PVS), and a higher average number of spermatozoa/oocyte (P < 0.05) in the zona and PVS. However, in the absence of ANP, caffeine and heparin, there were no oocytes with a spermatozoon in the PVS. There were no differences among ANP, caffeine or heparin treatments for the proportion of oocytes penetrated or average number of spermatozoa/oocyte in the zona and PVS. In conclusion, we inferred that ANP induced the acrosome reaction of preincubated giant panda spermatozoa by a PKG pathway. Furthermore, ANP enhanced the penetrability of porcine salt-stored oocytes by frozen-thawed giant panda spermatozoa.

Acrosome Reaction↗

Building capacity for health promotion--a case study from China.

During the period 1997-2000 a technical assistance project to build capacity for community-based health promotion was implemented in seven cities and one province in China. The technical assistance project formed part of a much larger World Bank supported program to improve disease prevention capabilities in China, commonly known as Health VII. The technical assistance project was funded by the Australian Agency for International Development. It was designed to develop capacity within the Ministry of Health (MOH) and the cities and province in the management of community-based health promotion projects, as well as supporting institutional development and public health policy reform. There are some relatively unique features of this technical assistance which helped shape its implementation and impact. It sought to provide the Chinese MOH and the cities and province with an introduction to comprehensive health promotion strategies, in contrast to the more limited information, education and communication strategies. The project was provided on a continuing basis over 3 years through a single institution, rather than as a series of ad hoc consultancies by individuals. Teaching and learning processes were developmental, leading progressively to a greater degree of local Chinese input and management to ensure sustainability and maintenance of technical support for the project. Based on this experience, this paper presents a model for capacity building projects of this type. It describes the education, training and planning activities that were the key inputs to the project, as well as the limited available evidence on the impact of the project. It describes how the project evolved over time to meet the changing needs of the participants, specifically how the content of the project shifted from a risk-factor orientation to a settings-based focus, and the delivery of the project moved from an expert-led approach to a more participatory, problem based learning approach. In terms of impact, marked differences before and after the implementation of the training activities were identified in key areas for reform, in addition to the self reported positive change in knowledge, and a high level of participant satisfaction. Key lessons are summarized. Technical assistance projects of this kind benefit from continuity and a high level of coordination, the provision of culturally and linguistically appropriate teaching, and a clear understanding of the need to match workforce development with organizational/institutional development.

China↗

Boronolectins and fluorescent boronolectins: an examination of the detailed chemistry issues important for the design.

Glycans in the form of glycoproteins or glycolipids play very critical roles in various biological and pathological processes including inflammation, cancer metastasis, immune reactions, embryo development, cell-cell communications and adhesions, blood generation, etc. Proteins (lectins) that can recognize carbohydrates have played very important roles in studying glycobiology. Small molecule mimics of lectins will be very useful in the development of new therapeutics and diagnostics. Along this line, boronic acids have been widely used in the design and synthesis of small organic compounds that mimic the function of lectins. This review examines in detail the factors that are important for the design of boronic acid-based lectin mimics, boronolectins.

Animals↗

Application of fluorescence-based resistance gene analog analysis for genotyping plant genetic resources.

Conventional approaches for detecting disease resistance gene analogs (RGAs) in plants are based on agarose gels or on polyacrylamide gel electrophoresis (PAGE) in combination with silver staining or radioactive labeling. A modified method for RGA analysis has been developed by using fluorescence-labeled primers for PCR amplifications. The amplified fragments are detected by denaturing PAGE using an automated laser fluorescence DNA sequencer and analyzed by fragment analysis software. This technique is not limited to specific plant species and is suitable for high-throughput genotyping plant genetic resources. We demonstrate here the efficiency of this method for comparison of RGA patterns in diverse plant species and for genotyping of natural populations of the wheat progenitor, Triticum dicoccoides.

Electrophoresis, Gel, Two-Dimensional↗

Disrupted tonotopy of the auditory cortex in mice lacking M1 muscarinic acetylcholine receptor.

Sensory cortices have multiple and distinct functional maps that systematically represent environmental information. Development of these maps is precisely controlled by a number of intrinsic and extrinsic factors. Cortical cholinergic regulation is a crucial factor for normal cortical morphogenesis. In this study, we test the role of the M1 muscarinic acetylcholine receptor, the main muscarinic receptor subtype in the neocortex in the development of tonotopic maps in the auditory cortex. Mice lacking M1 receptors have normal hearing sensitivity but exhibit disrupted tonotopic organization and frequency tuning in the auditory cortex. In contrast, tonotopic organization and frequency tuning remain normal in the auditory midbrain. In addition, cortical layer IV neurons of M1 mutants exhibit significantly shorter or sparser dendrites compared to neurons of wildtype mice. In summary, our data suggest that the M1 receptor appears to be critical for the refinement or normal maturation of cortical tonotopy that is guided by thalamocortical inputs during early development.

Acoustic Stimulation↗

Different expression patterns of duplicated PHANTASTICA-like genes in Lotus japonicus suggest their divergent functions during compound leaf development.

Recent studies on leaf development demonstrate that the mechanism on the adaxial-abaxial polarity pattern formation could be well conserved among the far-related species, in which PHANTASTICA (PAHN)-like genes play important roles. In this study, we explored the conservation and diversity on functions of PHAN-like genes during the compound leaf development in Lotus japonicus, a papilionoid legume. Two PHAN-like genes in L. japonicus, LjPHANa and LjPHANb, were found to originate from a gene duplication event and displayed different expression patterns during compound leaf development. Two mutants, reduced leaflets1 (rel1) and reduced leaflets3 (rel3), which exhibited decreased adaxial identity of leaflets and reduced leaflet initiation, were identified and investigated. The expression patterns of both LjPHANs in rel mutants were altered and correlated with abnormalities of compound leaves. Our data suggest that LjPHANa and LjPHANb play important but divergent roles in regulating adaxial-abaxial polarity of compound leaves in L. japonicus.

Amino Acid Sequence↗

Computational analysis of 3'-ends of ESTs shows four classes of alternative polyadenylation in human, mouse, and rat.

Alternative initiation, splicing, and polyadenylation are key mechanisms used by many organisms to generate diversity among mature mRNA transcripts originating from the same transcription unit. While previous computational analyses of alternative polyadenylation have focused on polyadenylation activities within or downstream of the normal 3'-terminal exons, we present the results of the first genome-wide analysis of patterns of alternative polyadenylation in the human, mouse, and rat genomes occurring over the entire transcribed regions of mRNAs using 3'-ESTs with poly(A) tails aligned to genomic sequences. Four distinct classes of patterns of alternative polyadenylation result from this analysis: tandem poly(A) sites, composite exons, hidden exons, and truncated exons. We estimate that at least 49% (human), 31% (mouse), and 28% (rat) of polyadenylated transcription units have alternative polyadenylation. A portion of these alternative polyadenylation events result in new protein isoforms.

Alternative Splicing↗

Sound-guided shaping of the receptive field in the mouse auditory cortex by basal forebrain activation.

The mammalian auditory cortex undergoes continuous plasticity following auditory experience. This study demonstrates the instructive roles of sound frequency and amplitude in representational plasticity in the primary auditory cortex of the mouse. Electrical stimulation of the basal forebrain paired with a tone led to a pronounced shift in the receptive field of the cortical neurons in both frequency and amplitude domains, the shift being towards the frequency and amplitude of the tone. Importantly, the plasticity in the frequency tuning of cortical neurons appeared to be largely dependent upon frequency-specific decreases in the response threshold. The minimum threshold of cortical neurons could be reduced only if the amplitude of the presented tone was lower than the minimum threshold. This finding suggests that training with low-intensity sound can increase the sensitivity of cortical neurons. Furthermore, all of these effects evoked by basal forebrain activation could be eliminated by cortical application of atropine, the acetylcholine muscarinic receptor antagonist. The data suggest that cortical plasticity is guided by both sound frequency and amplitude. The basal forebrain promotes sound-guided cortical plasticity by facilitating neural mechanisms intrinsic to the auditory system.

Acoustic Stimulation↗

Corticofugal feedback for auditory midbrain plasticity elicited by tones and electrical stimulation of basal forebrain in mice.

The auditory cortex (AC) is the major origin of descending auditory projections and is one of the targets of the cholinergic basal forebrain, nucleus basalis (NB). In the big brown bat, cortical activation evokes frequency-specific plasticity in the inferior colliculus and the NB augments this collicular plasticity. To examine whether cortical descending function and NB contributions to collicular plasticity are different between the bat and mouse and to extend the findings in the bat, we induced plasticity in the central nucleus of the mouse inferior colliculus by a tone paired with electrical stimulation of the NB (hereafter referred to as tone-ES(NB)). We show here that tone-ES(NB) shifted collicular best frequencies (BFs) towards the frequency of the tone paired with ES(NB) when collicular BFs were different from tone frequency. The shift in collicular BF was linearly correlated to the difference between collicular BFs and tone frequencies. The changes in collicular BFs after tone-ES(NB) were similar to those found in the big brown bat. Compared with cortical plasticity evoked by tone-ES(NB), the pattern of collicular BF shifts was identical but the shifting range of collicular BFs was narrower. A GABA(A) agonist (muscimol) or a muscarinic acetylcholine receptor antagonist (atropine) applied to the AC completely abolished the collicular plasticity evoked by tone-ES(NB). Therefore, our findings strongly suggest that the AC plays a critical role in experience-dependent auditory plasticity through descending projections.

Acoustic Stimulation↗

Yeast whole glucan particle (WGP) beta-glucan in conjunction with antitumour monoclonal antibodies to treat cancer.

Beta-glucans, biological response modifiers (BRMs) derived from the cell walls of yeast and other sources, have been demonstrated to prime leukocyte complement receptor 3 (CR3), thus enabling these cells to kill tumours opsonised with complement fragment iC3b. Many tumours activate complement via the classical pathway mediated by antitumour monoclonal antibodies (mAbs) or natural antibodies. Studies into the cellular and molecular mechanisms of action have demonstrated that orally administrated yeast beta-glucans are ingested and processed by macrophages. These macrophages secrete the active moiety that primes neutrophil CR3 to kill iC3b-opsonised tumour cells. Extensive studies in preclinical animal tumour models have demonstrated the efficacy of combined oral particulate yeast beta-glucan with antitumour mAb therapy in terms of tumour regression and long-term survival. It is proposed that the addition of beta-glucan will further improve the clinical therapeutic efficacy of antitumour mAbs in cancer patients.

Animals↗

[Vasoinhibitory effect of daltepartin sodium on human hepatocellular carcinoma in nude mice].

OBJECTIVES: To study the inhibition effect of Daltepartin Sodium (low molecular weight heparins) on human hepatocellular carcinoma (HCC) in nude mice. METHODS: Metastatic model of HCC was established in nude mice. The model mice were randomly divided into 4 groups; they were the control group (saline solution), chemotherapy group (fluorouracil and Cis-dichlorodiamine platinum), Daltepartin Sodium group (Daltepartin Sodium), combined treatment group (Daltepartin Sodium and chemotherapy). Tumor sizes, tumor inhibition rates, tumor metastases, intratumoral microvessel density (MVD), CD31 and AFP were evaluated. RESULTS: In comparison with the control and the chemotherapy group, the tumor sizes of the Daltepartin Sodium and the combined treatment group were significantly smaller; the tumor inhibitor rates were 0% versus 93.6%, 76.7%, 78.0%; MVD were 20.7+/-6.8 versus 18.2+/-2.6, 4.8+/-1.8 and 6.5+/-2.4; CD31 were 31.8+/-5.7 versus 25.5+/-5.1, 21.6+/-4.8 and 19.6+/-2.4; The incidence of liver metastasis was 80%, versus 70%, 20% and 10%; lung metastasis was 70% versus 60%, 20% and 10%; the peritoneal metastasis was 90% versus 60%, 30%and 30%. AFP were 121.8 ng/ml+/-31.4 ng/ml versus 21.5 ng/ml+/-13.3 ng/ml, 75.6 ng/ml+/-29.7 ng/ml and 55.8 ng/ml+/-38.0 mg/ml. Inhibiting effects of growth and metastasis of HCC in chemotherapy, Daltepartin Sodium and combined treatment groups were significantly different from those of the control group (F=9.191, P < 0.01), Daltepartin Sodium inhibited the angiogensis in the tumors more effectively than that in the control and chemotherapy groups (F=4.937, P < 0.01). CONCLUSION: Daltepartin Sodium can inhibit tumor growth and metastasis by inhibiting tumor angiogenesis in our nude mice HCC model.

Angiogenesis Inhibitors↗

[Study on the inhibitory effects of juice of tomato on the growth of human prostate carcinoma PC-3 cells].

OBJECTIVE: To study on the inhibitory effects of juice of tomato on the growth of human prostate carcinoma PC-3 cells and its possible mechanism. METHODS: PC-3 cells were treated with the juice of tomato in different concentration (40, 80, 120 ul/ml) for 48h; the proliferation of PC-3 cells were measured by MTT assay, the comet assay was used to measure the DNA damage of PC-3 cells. RESULTS: Juice of tomato could inhibit the proliferation of PC-3 cells, the growth inhibitory rate of experimental groups were significantly higher than that of control group, with very statistical significance; and it could induce the breakage of DNA single strand of PC-3 cells and resulted in comet cells with tail, Rate of DNA tail and the tail length of DNA increased with the increasing of concentration of juice of tomato, showing the obvious dose effect relationship. CONCLUSION: Juice of tomato could lead to DNA damage of PC-3 cells, it was related to that could inhibit the proliferation of PC-3 cells.

Beverages↗

[Diagnostic value of echocardiography for cardiac tumors in infancy and childhood].

OBJECTIVE: The present study was designed to evaluate the clinical manifestations, surgical findings, pathologic types and treatment of cardiac tumor and to analyze the echocardiographic characteristics of the cases. METHODS: Records of 19 patients with cardiac tumors confirmed by operations and pathology at Fuwai Cardiovascular Hospital in Beijing, China between Jan, 1983 and Dec, 2003 were reviewed. Clinical and echocardiographic data of all patients were analyzed. RESULTS: The median age of patients was 7 +/- 5 years, ranging from 5 months to 14 years. There were 8 male and 11 female cases. The surgical findings revealed that 57.9% (11 cases) of cardiac tumors were found in left heart, 36.8% (7 cases) in right heart, 5.3% (1 case) in two ventricles. The pathological study revealed that 17 cases (89.5%) were diagnosed as primary cardiac benign tumors including myxoma in 10 cases (52.6%), rhabdomyoma in 4 cases (21.1%), fibroma in 2 cases (10.5%) and lipoma in 1 case (5.3%). Two cases were diagnosed (10.5%) as cardiac malignant tumors including a primary cardiac rhabdomyosarcoma and a metastatic epithelioid sarcoma. By using echocardiography 11 cases were diagnosed as myxomas and rhabdomyoma (11/19, 57.9%), 8 cases were diagnosed as space occupying lesions of the heart or myxoma (8/19, 42.1%). CONCLUSIONS: Myxomas are the most common heart tumors seen in infancy and childhood, followed in frequency by rhabdomyomas, fibromas and lipomas. Surgery is recommended for patients with refractory and severe clinical symptoms.

Adolescent↗