Biomedical subjects

Yan Deng

Publications and source records attributed to Yan Deng.

At least 19 recordsLinked to original sources

PubMed2026

Cardiomyocyte-Specific Plakophilin-2 Loss Is Sufficient to Induce Aging and Senescence of Nonmyocytes: Relevance to Arrhythmogenic Cardiomyopathy.

BACKGROUND: Pathogenic variants in PKP2 are the most common cause of familial arrhythmogenic right ventricular cardiomyopathy. This study tests whether plakophilin-2 (PKP2) deficiency only in cardiomyocytes is sufficient to provoke premature aging and proinflammatory senescence in nonmyocyte, cardiac resident cells. METHODS: We studied mice with cardiomyocyte-specific, tamoxifen-activated loss of PKP2 (cardiomyocyte-specific conditional knockout of plakophilin-2) using conventional and multiplex imaging, cytokine arrays, epigenetic clocks, spatial transcriptomics, expansion and structured illumination microscopy, and correlative data analysis. We examined nonmyocytes and cardiomyocytes for premature aging and senescence. RESULTS: We observed senescence-associated heterochromatin foci in nonmyocytes, predominantly in cells positive for α-smooth muscle actin staining. Cytokines in media of nonmyocyte cells were consistent with senescence-associated secretory phenotype. Epigenetic clocks identified premature aging. Multiplex immunohistochemistry showed nonmyocyte cells in niches, intermingled with cardiomyocytes. Spatial transcriptomics showed overrepresentation of senescence-associated secretory phenotype-related transcripts, predominantly in myocyte-rich areas of the left ventricle. Senescence-associated heterochromatin foci and increased epigenetic age were not found in cardiomyocytes from cardiomyocyte-specific conditional knockout of plakophilin-2 hearts, although we observed structural features associated with premature aging. Cross-reference analysis showed correlation between the cardiomyocyte-specific conditional knockout of plakophilin-2 cardiac proteome and that of mice 5 or 6 times their chronological age, as well as transcriptional signatures of neurodegenerative diseases. CONCLUSIONS: Loss of PKP2 expression only in adult cardiac myocytes is sufficient to induce proinflammatory senescence in nonmyocytes, and overall premature cardiac aging. This is the first study to intersect cellular senescence and premature aging with desmosomal arrhythmogenic cardiomyopathies. We speculate that cell-agnostic molecular signatures, biomarkers, and pharmacology of senescence and of neurodegenerative diseases may be relevant to diagnose or treat PKP2 arrhythmogenic right ventricular cardiomyopathy.

Animals↗

PubMed2006

Macrophages regulate the angiogenic switch in a mouse model of breast cancer.

The development of a tumor vasculature or access to the host vasculature is a crucial step for the survival and metastasis of malignant tumors. Although therapeutic strategies attempting to inhibit this step during tumor development are being developed, the biological regulation of this process is still largely unknown. Using a transgenic mouse susceptible to mammary cancer, PyMT mice, we have characterized the development of the vasculature in mammary tumors during their progression to malignancy. We show that the onset of the angiogenic switch, identified as the formation of a high-density vessel network, is closely associated with the transition to malignancy. More importantly, both the angiogenic switch and the progression to malignancy are regulated by infiltrated macrophages in the primary mammary tumors. Inhibition of the macrophage infiltration into the tumor delayed the angiogenic switch and malignant transition whereas genetic restoration of the macrophage population specifically in these tumors rescued the vessel phenotype. Furthermore, premature induction of macrophage infiltration into premalignant lesions promoted an early onset of the angiogenic switch independent of tumor progression. Taken together, this study shows that tumor-associated macrophages play a key role in promoting tumor angiogenesis, an essential step in the tumor progression to malignancy.

Animals↗

PubMed2006

Progesterone blocks estrogen-induced DNA synthesis through the inhibition of replication licensing.

In the uterus, progesterone (P4) acts early in G1 as a physiological inhibitor of estradiol-17beta (E2)-induced epithelial cell proliferation. Gene expression profiling of uterine epithelial cell RNA isolated 3 h after hormonal treatment of ovariectomized mice revealed the co-coordinate down-regulation by P4 of >20 genes whose functions are associated with DNA replication. This group included all of the minichromosome maintenance (MCM) proteins that are required for DNA replication licensing. E2 regulated loading of these MCM proteins onto chromatin in parallel with its induction of DNA synthesis. E2 caused this chromatin loading by retention of MCM proteins in the nucleus and through the induction of the loading factor Cdt1, which is necessary for the MCM heterohexamer to bind to the origin of DNA replication. P4 dramatically reduced the binding of the MCMs to chromatin by a number of mechanisms. First, MCM mRNA and protein abundance was down-regulated. Second, P4 inhibited the E2 induction of Cdt1. Third, P4 treatment sequestered the normally nuclear MCM proteins into the cytoplasm. This reduced MCM binding resulted in the complete inhibition of E2-induced DNA synthesis by P4. These data reveal mechanisms not only for female sex steroid hormone action but also in the regulation of DNA replication licensing.

Animals↗

PubMed2006

Microarray analysis of uterine epithelial gene expression during the implantation window in the mouse.

In mice, the uterus becomes transiently receptive to the hatched blastocyst on the day of implantation to allow its attachment to the luminal epithelium and subsequent invasion into the uterus. This uterine preparation for implantation is regulated by estradiol-17beta and progesterone, acting through their transcription factor receptors. Using ovariectomized mice treated with physiological regimens of these hormones, combined with methods to isolate RNA specifically from the uterine epithelium followed by transcriptome analysis on cDNA microarrays, 222 genes whose transcript abundance was specifically increased by estradiol-17beta and progesterone treatment were identified. Gene ontology analysis revealed an emphasis on genes involved with immune responses, extracellular matrix metabolism, and cell-to-cell communication. In situ hybridization to uterine sections isolated through the first 6 d of pregnancy identified novel sets of genes such as Bach, Myd88, Cd14, Isg20, and Lrp2 whose expression was restricted to the uterine epithelium during the implantation window. Particularly notable was the expression of the mRNA for members of the signaling pathway from the Toll-like receptors to its downstream targets such as Irg-1. The identification of these genes showing a cell type hormonally regulated pattern of expression in the uterus suggests novel functions for them during implantation.

Animals↗

PubMed2006

[Study on the methods for detection of Toxoplasma antigen].

A sandwich ELISA was established with monoclonal antibody as detecting antibody and rabbit anti-Toxoplasma polyclonal antibody as capturing antibody. ABC (avidin-biotin-peroxidase complex)-ELISA and immuno-PCR were also used to detect different concentrations of Toxoplasma antigen. The lowest concentration of antigen to be detected by sandwich ELISA, ABC-ELISA and immuno-PCR was 0. 6 microg/ml, 0. 075 microg/ml and 0.1 ng/ml respectively. The immuno-PCR shows a much higher sensitivity than the other two methods.

Animals↗

PubMed2005

Progesterone inhibits the estrogen-induced phosphoinositide 3-kinase-->AKT-->GSK-3beta-->cyclin D1-->pRB pathway to block uterine epithelial cell proliferation.

The mammalian cell cycle is regulated by the cyclin/cyclin-dependent kinase (CDK) phosphorylation of the retinoblastoma (pRB) family of proteins. Cyclin D1 with its CDK4/6 partners initiates the cell cycle and acts as the link between extracellular signals and the cell cycle machinery. Estradiol-17beta (E2) stimulates uterine epithelial cell proliferation, a process that is completely inhibited by pretreatment with progesterone (P4). Previously, we identified cyclin D1 localization as a key point of regulation in these cells with E2 causing its nuclear accumulation and P4 retaining it in the cytoplasm with the resultant inhibition of pRB phosphorylation. Here we show that E2 stimulates phosphoinositide 3-kinase to activate phosphokinase B/AKT to effect an inhibitory phosphorylation of glycogen synthase kinase (GSK-3beta). This pathway is suppressed by P4. Inhibition of the GSK-3beta activity in P4-treated uteri by the specific inhibitor, LiCl, reversed the nuclear accumulation of cyclin D1 and in doing so, caused pRB phosphorylation and the induction of downstream genes, proliferating cell nuclear antigen and Ki67. Conversely, inhibition of phosphoinositide 3 kinase by LY294002 or Wortmanin reversed the E2-induced GSK-3beta Ser9 inhibitory phosphorylation and blocked nuclear accumulation of cyclin D1. These data show the reciprocal actions of E2 and P4 on the phosphoinositide 3-kinase through to the GSK-3beta pathway that in turn regulates cyclin D1 localization and cell cycle progression. These data reveal a novel signaling pathway that links E2 and P4 action to growth factor-mediated signaling in the uterus.

Animals↗

PubMed2005

[A clinical study on the effect of Yinxing Damo combined with betahistine hydrochloride injection on vertebral basilar artery ischemic vertigo].

OBJECTIVE: To evaluate the therapeutic efficacy of Yinxing Damo (YXDM) combined with Betahistine Hydrochloride Injection (BHI) on vertebra basilar artery ischemic vertigo (VBIV). METHODS: Ninety patients with VBIV were randomly divided into two groups; 45 patients (the treated group) were treated with YXDM and BHI intravenous dripping, once a day for 14 days. Another 45 patients (control group) were treated with Xueshuantong and BHI intravenous dripping, once daily for 14 days. The clinical syndromes and the index of the transcranial Doppler (TCD) and hemorheology were observed. RESULTS: The total effective rate was 100% in the treated group, which was better than that in the control group 90.5%, (P < 0.05). The indexes of TCD and hemorheology in the treated group were obviously improved after treatment, (P < 0.01). CONCLUSION: YXDM combined with BHT injection had better effect in treating patients with VBIV is an ideal drug for VBIV.

Adult↗

PubMed2004

Materials design in the performance of all-ceramic crowns.

Results from a systematic study of damage in material structures representing the basic elements of dental crowns are reported. Tests are made on model flat-layer specimens fabricated from various dental ceramic combinations bonded to dentin-like polymer substrates, in bilayer (ceramic/polymer) and trilayer (ceramic/ceramic/polymer) configurations. The specimens are loaded at their top surfaces with spherical indenters, in simulation of occlusal function. The onset of fracture is observed in situ using a video camera system mounted beneath the transparent polymer substrate. Critical loads to induce fracture and deformation at the ceramic top and bottom surfaces are measured as functions of layer thickness and contact duration. Radial cracking at the ceramic undersurface occurs at relatively low loads, especially in thinner layers. Fracture mechanics relations are used to confirm the experimental data trends, and to provide explicit dependencies of critical loads in terms of key variables: material-elastic modulus, hardness, strength and toughness; geometric-layer thicknesses and contact radius. Tougher, harder and (especially) stronger materials show superior damage resistance. Critical loads depend strongly (quadratically) on crown net thickness. The analytic relations provide a sound basis for the materials design of next-generation dental crowns.

Biocompatible Materials↗

PubMed2004

[Hominis placenta promotes melanocyte proliferation melanin synthesis and tyrosinase activity in vitro].

OBJECTIVE: To investigate the effects of Hominis placenta on melanocytes and tyrosinase activity in vitro. METHODS: MTT assay was used to assess the proliferation of melanocytes treated with Hominis placenta. Hunt method was employed to determine melanin synthesis and the oxidation rate of DL-dopa to evaluate the tyrosinase activity. RESULTS: Hominis placenta promoted melanocyte proliferation (P<0.01) and significantly increased the cell number (P<0.01), melanin synthesis (P<0.01), with the optimal concentration of 0.1g/L (P<0.01), and also enhanced tyrosinase activity (P<0.01) at the optimal concentration of 1 g/L (P<0.01). CONCLUSION: Hominis placenta promotes proliferation, melanin synthesis and tyrosinase activity of the melanocytes.

Cell Proliferation↗

PubMed2003

Fracture of ceramic/ceramic/polymer trilayers for biomechanical applications.

Fracture damage in trilayers consisting of outer and inner brittle layers bonded to a compliant (polycarbonate) substrate and subjected to concentrated surface loading is analyzed. The principal mode of fracture is radial cracking at the undersurface of the inner (core) layer, even in the strongest of core ceramics--other damage modes, including radial cracking in the outer (veneer) layer, are less invasive in these all-brittle coating systems. Tests on simple trilayer structures fabricated from glasses, sapphire, and dental ceramics are used to examine the dependence of the critical load for radial fracture in terms of relative outer/inner layer thickness and modulus, and inner layer strength. An explicit relation for the critical load, based on a flexing plate model in which the outer/inner bilayer is reduced to an "equivalent" monolithic coating with "effective" composite modulus, is used to examine these dependencies. The theoretical relation describes all the major trends in the critical load data over a broad range of variables, thus providing a sound basis for trilayer design. Relevance of the analysis to dental crowns and other biomechanical applications is a central theme of the study.

Biocompatible Materials↗

PubMed2003

Quantitative analysis of sinoatrial node using Doppler tissue images.

A method has been developed to quantitatively analyze sinoatrial nodes (SAN) using Doppler tissue images (DTI). Doppler tissue images of SAN are acquired using an intracardiac catheter via the superior vena cava in an in vivo experiment. A sequence of DTI images of a SAN is obtained, and a complete cycle of the SAN excitation is observed. The tissue acceleration of the SAN is extracted and quantitatively analyzed. The estimated time-acceleration curve of the SAN exhibits remarkable similarity to the electrocardiogram curve. This is the first report on such finding. The experimental results show that the tissue movement of the SAN correlates with electrical cardiac activities and closely associates with the different phases of the cardiac cycle. This method has great potential in characterizing the local cardiac activities through the study of the conduct pathway.

Acceleration↗

PubMed2003

Effect of Angelica sinensis (Oliv.) on melanocytic proliferation, melanin synthesis and tyrosinase activity in vitro.

OBJECTIVE: To investigate the effects of Angelica sinensis (Oliv.) on melanocytes and tyrosinase activity. METHODS: MTT method and cleavage by NaOH were employed to measure the proliferation and melanin synthesis of melanocytes, respectively. Tyrasinase activity assessment was performed by measuring the rate of oxidation of DL-dopa. RESULTS: Angelica sinensis (Oliv.) was found to promote melanocytic proliferation (P < 0.05), resulting in a statistically significant increase in the cell counts (P < 0.05). It also enhanced melanin synthesis (P < 0.05) and tryosinase activity (P < 0.05) of the melanocytes, and the most potent effects were achieved at the concentration of 1 g/L (P < 0.05). CONCLUSION: Angelica sinensis (Oliv.) promotes melanocytic proliferation, melanin synthesis and tyrosinase activity, which may be the mechanism for validating its clinical use in the treatment of skin pigmentation.

Angelica sinensis↗

PubMed2003

Enhancement of antitumor effect of cisplatin against human ovarian carcinoma cells by mifepristone in vivo.

OBJECTIVE: To investigate in vivo the enhancement by mifepristone (RU486) of the antitumor effect of cisplatin (DDP) on human ovarian carcinoma. METHODS: mouse models bearing xenografted cisplatin-resistant ovarian carcinoma were established, in which the changes in tumor volume and the morphology of the implanted tumors were compared before and after treatment with RU486 and DDP. The expression of glucosylceramide synthase (GcS) mRNA was detected by reverse transcriptase-PCR. RESULTS: The morphology of the tumors in RU486 plus DDP group was significantly different as compared with that of the control group. In comparison with exclusive DDP treatment, combined treatment with RU486 and DDP resulted in significantly greater inhibition rates of the tumors (70.48% vs 21.55%, P < 0.01). GcS mRNA expression was lowered in both RU486 plus DDP and RU486 groups, especially in the former group, as compared with that in control group. CONCLUSION: At a non-toxic dose, RU486 may enhance the sensitivity of tumor cells to cisplatin in vivo, possibly through the mechanism of inhibiting GcS expression at the mRNA level.

Abortifacient Agents, Steroidal↗

PubMed2003

A genetic algorithm for detecting target geometric figures.

A genetic algorithm is proposed to detect target geometric figures in an given image. Float-point encoding was adopted to process the parameters of a geometric figures to be detected. On the basis of classical Hough transform, a fitness function was obtained for each individual task, and the individuals with the highest fitness function were identified and copied into the cohort of the next generation. For the rest of the individuals, operation with multi-point crossover or uniform mutation was performed to form new individuals in the next generation. When the termination conditions for this genetic algorithm were met, the best-fitted individual was decoded and output as the parameters of the detected geometric figures. This algorithm can eliminate noise interference with good convergence and accurate results, and may save time and storage space during relatively easily programmed computation in comparison with classical Hough transform.

Algorithms↗

PubMed2003

Observation of the short-term therapeutic effect of 3D conformal hypofractionated single high-dose radiotherapy on lung tumors.

OBJECTIVE: To evaluate the short-term effects of 3D conformal hypofractionated single high-dose radiotherapy for lung tumors. METHODS: Thirty-four patients with lung tumors that defied surgical removal were treated with 3D conformal hypofractionated single high-dose radiotherapy, and the short-term therapeutic effects and survival rates of the patients were assesses. RESULTS: In 31 (91.2%) of the patients, the local tumor growth was successfully controlled, with the 1-, 2-, and 3- year survival rates of 88.2% (30/34), 35.3% (12/34), and 26.5% (9/34), respectively. CONCLUSION: 3D conformal hypofractionated single high-dose radiotherapy is effective and feasible approach for unresectable lung tumors judging from the short-term effects, but its long-term efficacy awaits further study.

Aged↗

PubMed2003

[Apoptosis-inducing effect of palmitic acids on rat pancreatic islet cells in primary culture: a preliminary study].

OBJECTIVE: To investigate the in vitro apoptosis-inducing effect of palmitic acid on pancreatic islet cells in primary culture, thereby to understand the role of palmitic acid in the pathogenesis of type 2 diabetes mellitus. METHOD: SD rat pancreatic islet cells were isolated and cultured in monolayer in vitro followed by incubation with stepwise diluted palmitic acid (0, 0.125, 0.25 mmol/L and 0.5 mmol/L respectively), and the insulin concentrations in the culture medium were determined by radio immunological methods. Morphological observation with a fluorescence microscope was conducted after double staining of the cells with PI/Hoechst 33342. RESULTS: The glucose-stimulated insulin secretion was inhibited by palmitic acid at the concentration of 0.25 and 0.5 mmol/L, which also induced obvious cell apoptosis. CONCLUSION: Palmitic acid is capable of inducing islet cell apoptosis in a dose-dependent manner.

Animals↗

PubMed2003

[Detection of nuclear factor kappa B by immunochemical staining and image analysis].

OBJECTIVE: To find a relatively simple and safe method for quantitative assay of nuclear factor (NF)-kappa B activity. METHODS: Immunochemical staining of NF-kappa B/p65 subunit with its antibody was performed in human umbilical vein endothelial cells stimulated with advanced glycation end products-modified human serum albumin (AGE-HSA). The ratio of p65 subunit staining in the nuclei and cytoplasm was determined by means of imaging analysis, and the results were compared with those of electrophoretic mobility shift assay (EMSA). RESULTS: NF-kappa B could be activated by AGE-HSA in a time- and dose-dependent manner, and the results obtained from immunochemical staining were consistent with those from EMSA. CONCLUSION: p65 immunochemical staining and subsequent image analysis is feasible in the quantitative detection of NF-kappa B activation.

Electrophoretic Mobility Shift Assay↗

PubMed2003

[Acute respiratory tract obstruction during thyroid operation: analysis of 10 cases].

OBJECTIVE: To explore the causes and management of acute respiratory tract obstruction in patients undergoing thyroid operation. METHODS: A retrospective review was conducted in 10 such cases that we encountered in our 11 years' experience with thyroid operation. RESULTS: Respiratory tract obstructions occurred in 10(0.31%) of 3,186 cases during thyroid operation. The causes for the obstructions included tracheomalacia in 2 cases, hematoma compression in 5 cases, trachea convulsion in 2 cases and phlegm obstruction in 1 case. Tracheotomy or intratracheal intubation was performed in 6 cases and hematoma removal in 4 cases, with the occurrence of death in 1 case. CONCLUSION: Hematoma compression and tracheomalacia etc. are among the most common causes of acute respiratory tract obstruction during thyroid operation, the occasion of which demands immediate implementation of tracheotomy or intratracheal intubation.

Acute Disease↗