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Biomedical subjects

Ying Cao

Publications and source records attributed to Ying Cao.

At least 37 records · Page 2Linked to original sources

Human adipose tissue-derived stem cells differentiate into endothelial cells in vitro and improve postnatal neovascularization in vivo.

In this study, we isolated CD31(-), CD34(-), CD106(-) (VCAM-1(-)), and fetal liver kinase(+) (Flk1(+)) cells from adipose tissue. These cells can be induced to differentiate into cells of osteogenic and adipogenic lineages in vitro and were termed adipose derived adult stem cells (ADAS cells). We also showed that they have characteristics of endothelial progenitor cells. In vitro, ADAS cells expressed endothelial markers when cultured with VEGF. In vivo, ADAS cells can differentiate in response to local cues into endothelial cells that contributed to neoangiogenesis in hindlimb ischemia models. PI3 kinase inhibitor LY294002 blocked the differentiation of ADAS cells into endothelial cells in vitro. Because ADAS cells can be expanded in culture without obvious senescence for more than 20 population doublings, they may be a potential source of endothelial cells for cellular pro-angiogenic therapies.

Adipocytes↗

[Effects of protein tyrosine kinase within the brainstem nucleus tractus solitarius on the ventilatory responses of peripheral chemoreflex].

The aim of the present study was to observe whether protein tyrosine kinase (PTK) within the nucleus tractus solitarius (NTS) was involved in the regulation of ventilatory responses of peripheral chemoreflex. The experiments were performed on anesthetized, immobilized and artificially ventilated rabbits. Peripheral chemoreflex was elicited by ventilating the animal with 10% O2-balance 90% N2. Changes in the peak amplitude and frequency of integrated phrenic nerve activity were observed. The ventilatory responses of peripheral chemoreflex following 0.1 microl microinjection within the NTS of either PTK inhibitor genistein (10 mol/L), AMPA glutamate receptor inhibitor CNQX (10 mol/L),or inactive PTK inhibitor daidzein (10 mol/L) were recorded. The results are as follows: Both genistein and CNQX attenuated the ventilatory responses of peripheral chemoreflex, while no changes occurred following daidzein. The amplitude of integrated phrenic nerve discharge and the phrenic burst frequency were decreased by (-21.77+/-6.93)% and (-24.70+/-7.61)% respectively after administration of genistein. CNQX resulted in similar decreases in the amplitude of phrenic nerve discharge (-27.13+/-7.63)% and the burst frequency (-21.34+/-4.88)%. In addition, the inhibitory effects of CNQX and genistein were the same whether they were applied alone or one after another, indicating that they had no cooperative effects. The results obtained suggest that PTK within the NTS regulates the peripheral chemoreflex control of respiration and that this regulation of PTK may be mediated through the phosphorylation of AMPA receptors in NTS neurons.

Animals↗

Osterix, a transcription factor for osteoblast differentiation, mediates antitumor activity in murine osteosarcoma.

Osterix is a novel zinc finger-containing transcription factor that is essential for osteoblast differentiation and bone formation. We hypothesized that osterix might have a role in osteosarcoma tumor growth and metastasis. Northern blot analysis showed that the mRNA level of osterix was decreased in two mouse osteosarcoma cell lines compared with its level in normal mouse osteoblasts. Osterix expression was also decreased in three human osteosarcoma cell lines. Transfection of the osx gene into the mouse osteosarcoma cells inhibited tumor cell growth in vitro and in vivo and significantly reduced tumor incidence, tumor volume, and lung metastasis following intratibial injection. Osterix expression was also associated with decreased osteolysis. Using an in vitro migration assay, osterix suppressed the migration of tumor cells to lung extracts. These results suggest that osterix expression may play a role in osteosarcoma tumor growth and metastasis.

Animals↗

Effect of PbII on the secondary structure and biological activity of trypsin.

The effects of Pb(II) on the secondary structure and biological activity of trypsin have been examined by monitoring changes in its conductivity and IR and circular dichroism (CD) spectra. The results show that Pb(II) reacts with trypsin, and that the binding sites might be -OH and -NH groups in pepsin. The CD spectra indicate that interaction with Pb(II) significantly affects the secondary structure of trypsin, the beta-sheet-structure content being increased by about 42%, whilst those of alpha-helix and beta-turn structures are decreased by 13% and 21%, respectively. The results clearly demonstrate that Pb(II) affects the biological activity of trypsin by modifying its secondary structure. Most interesting is that Pb(II) up-regulates the activity of trypsin at low concentrations while down-regulating it at high concentrations.

Binding Sites↗

A molecular docking model of SARS-CoV S1 protein in complex with its receptor, human ACE2.

The exact residues within severe acute respiratory syndrome coronavirus (SARS-CoV) S1 protein and its receptor, human ACE2, involved in their interaction still remain largely undetermined. Identification of exact amino acid residues that are crucial for the interaction of S1 with ACE2 could provide working hypotheses for experimental studies and might be helpful for the development of antiviral inhibitor. In this paper, a molecular docking model of SARS-CoV S1 protein in complex with human ACE2 was constructed. The interacting residue pairs within this complex model and their contact types were also identified. Our model, supported by significant biochemical evidence, suggested receptor-binding residues were concentrated in two segments of S1 protein. In contrast, the interfacial residues in ACE2, though close to each other in tertiary structure, were found to be widely scattered in the primary sequence. In particular, the S1 residue ARG453 and ACE2 residue LYS341 might be the key residues in the complex formation.

Amino Acid Sequence↗

Alpha-linolenic acid but not conjugated linolenic acid is hypocholesterolaemic in hamsters.

Conjugated linolenic acid (CLN) refers to a group of octadecatrienoic acid isomers that have three double bonds in conjugation. Both pomegranate and tung seed oils are rich in CLN but the major isomer in the former is cis9,trans11,cis13 while in the latter it is cis9,trans11,trans13. The present study examined the effects of CLN, isolated from either pomegranate seed oil or tung seed oil, and alpha-linolenic acid (LN), isolated from flaxseed oil, on serum cholesterol levels in male hamsters (body weight 105 g; age 10 weeks) fed a 0.1% cholesterol and 10% lard diet, for a period of 6 weeks. All hamsters were allowed free access to food and fluid. The blood samples were taken by bleeding from the retro-orbital sinus into a heparinized capillary tube under light ether anaesthesia after overnight fasting at weeks 0, 2, 4 and 6. It was found that supplementation of CLN at levels of 12.2-12.7 g/kg diet exhibited no significant effect on serum cholesterol level while LN at a similar level of supplementation had serum cholesterol reduced by 17-21% compared with the control diet containing no LN and CLN. Supplementation of CLN and LN significantly decreased hepatic cholesterol but no effect was observed on heart and kidney cholesterol levels. It was concluded that LN possessed hypocholesterolaemic activity while CLN had no effect on blood cholesterol, at least in hamsters.

Animals↗

Mitochondrial phylogenetics and evolution of mysticete whales.

The phylogenetic relationships among baleen whales (Order: Cetacea) remain uncertain despite extensive research in cetacean molecular phylogenetics and a potential morphological sample size of over 2 million animals harvested. Questions remain regarding the number of species and the monophyly of genera, as well as higher order relationships. Here, we approach mysticete phylogeny with complete mitochondrial genome sequence analysis. We determined complete mtDNA sequences of 10 extant Mysticeti species, inferred their phylogenetic relationships, and estimated node divergence times. The mtDNA sequence analysis concurs with previous molecular studies in the ordering of the principal branches, with Balaenidae (right whales) as sister to all other mysticetes base, followed by Neobalaenidae (pygmy right whale), Eschrichtiidae (gray whale), and finally Balaenopteridae (rorquals + humpback whale). The mtDNA analysis further suggests that four lineages exist within the clade of Eschrichtiidae + Balaenopteridae, including a sister relationship between the humpback and fin whales, and a monophyletic group formed by the blue, sei, and Bryde's whales, each of which represents a newly recognized phylogenetic relationship in Mysticeti. We also estimated the divergence times of all extant mysticete species, accounting for evolutionary rate heterogeneity among lineages. When the mtDNA divergence estimates are compared with the mysticete fossil record, several lineages have molecular divergence estimates strikingly older than indicated by paleontological data. We suggest this discrepancy reflects both a large amount of ancestral polymorphism and long generation times of ancestral baleen whale populations.

Animals↗

RBP-Jkappa/SHARP recruits CtIP/CtBP corepressors to silence Notch target genes.

Notch is a transmembrane receptor that determines cell fates and pattern formation in all animal species. After ligand binding, proteolytic cleavage steps occur and the intracellular part of Notch translocates to the nucleus, where it targets the DNA-binding protein RBP-Jkappa/CBF1. In the absence of Notch, RBP-Jkappa represses Notch target genes through the recruitment of a corepressor complex. We and others have identified SHARP as a component of this complex. Here, we functionally demonstrate that the SHARP repression domain is necessary and sufficient to repress transcription and that the absence of this domain causes a dominant negative Notch-like phenotype. We identify the CtIP and CtBP corepressors as novel components of the human RBP-Jkappa/SHARP-corepressor complex and show that CtIP binds directly to the SHARP repression domain. Functionally, CtIP and CtBP augment SHARP-mediated repression. Transcriptional repression of the Notch target gene Hey1 is abolished in CtBP-deficient cells or after the functional knockout of CtBP. Furthermore, the endogenous Hey1 promoter is derepressed in CtBP-deficient cells. We propose that a corepressor complex containing CtIP/CtBP facilitates RBP-Jkappa/SHARP-mediated repression of Notch target genes.

Alcohol Oxidoreductases↗

Statins and their roles in cancer.

The association of long-term statin use with cancer risk has recently become an interesting topic because of rather conflicting clinical evidence. On the one hand, early animal toxicology studies suggested the carcinogenicity of statins. On the other hand, although several large-scale, randomized clinical trials with secondary endpoints assessing associated cancer risk confirmed the safety of long-term statin use, results concerning the risk of specific cancer types remain inconclusive. To further complicate matters, retrospective studies concluded that the use of statins can actually reduce cancer risk. In addition, several small-scale cancer trials have shown evidence supporting the use of statins as therapeutic anticancer agents. In this review, we will discuss the results of the clinical studies, emphasize their strengths and weaknesses, and evaluate their potential impact on clinical practice.

Anticarcinogenic Agents↗

Renal neoplasms in younger adults: analysis of 112 tumors from a single institution according to the new 2004 World Health Organization classification and 2002 American Joint Committee on Cancer Staging System.

CONTEXT: Adult renal neoplasms have a predilection for older patients and are clinically and morphologically distinct from renal neoplasms found in pediatric age groups. Relatively rare tumors occur in younger adults (18-45 years of age). Whether these renal tumors are morphologically and clinically distinct from those of older adults has been the subject of controversy. Recent modification of the World Health Organization histologic classification and the American Joint Committee on Cancer staging system of adult renal tumors further highlighted the need for case analysis in this age group. OBJECTIVE: To analyze renal tumors in younger adults based on a large surgical series from a single institution. DESIGN: Of 780 renal mass nephrectomy (partial, total, or radical) specimens that were available for evaluation and had been obtained between 1986 and 2004 at Loyola University Medical Center, 112 specimens were from patients between 18 and 45 years of age. The tumors were reevaluated according to the 2004 World Health Organization classification and the 2002 American Joint Committee on Cancer staging system. RESULTS: The likelihood of clear cell renal cell carcinoma was significantly reduced from 65% in older adults to 53% in younger adults (18-45 years, P = .04). The reduction trend was more significant when comparing an even younger age group. The majority (64%) of clear cell renal cell carcinoma in younger adults was low stage, T1a. Seventeen percent of these tumors had multilocular cystic features involving more than 50% of the tumor volume (55%-85%). The number of oncocytomas was also significantly lower in younger adults than in older adults (2% vs 11%, P < .001), and this presumably age-related benign neoplasm was not identified in patients younger than 40 years in this study. In contrast, the miscellaneous tumor category showed a remarkable increase, from 4% in older adults to 26% in younger adults (P < .001). The youngest patient group (18-35 years) had a higher incidence of miscellaneous tumors, 37%. Younger female adults tended to have more benign miscellaneous neoplasms than did their male counterparts (64% vs 36%, P < .001). Clear cell and chromophobe renal cell carcinoma occurred more frequently in younger male adults than in female adults (2:1 and 8:1, respectively). CONCLUSIONS: Renal neoplasms are more heterogeneous in younger adults and have a different distribution pattern compared with that in older adults. Malignant and benign renal neoplasms tend to have a contrasting sex distribution in younger adults.

Adult↗

Sentinel node status and tumor characteristics: a study of 234 invasive breast carcinomas.

CONTEXT: Axillary lymph node status is the most important prognostic factor in patients with breast cancer. Tumor size and lymph node status, the most reliable pathologic bases of the tumor staging system, are practical parameters for estimating survival status. With the advent of lymphatic mapping and sentinel node (SN) identification, there is potential for a more efficient and sensitive evaluation of the axillary lymph node status. OBJECTIVE: To correlate SN status with tumor size, grade, and lymphovascular invasion. DESIGN: We examined 234 patients with unifocal breast carcinomas measuring 25 mm or less as detected by preoperative ultrasound during the period May 1998 through December 2002. Sentinel nodes were examined by frozen section and paraffin section as per protocol. RESULTS: Of the 234 patients, SN was identified in 221 (94.5%). An average of 1.38 SNs were examined per patient. Seventy-seven of 221 patients were SN positive on paraffin section. Sixty-six (85.7%) of these 77 cases could be correctly diagnosed as positive for metastatic carcinoma on frozen section. Two cases reported as positive on paraffin section were reported as suspicious on frozen section. Logistic regression indicated that tumor size, grade, and lymphovascular invasion were all significantly associated with SN status (P < .001). CONCLUSIONS: Tumor size, grade, and lymphovascular invasion were significantly associated with SN status in unifocal invasive breast carcinoma.

Axilla↗

[Potential of human adipose tissue derived adult stem cells differentiate into endothelial cells].

OBJECTIVE: To investigate whether human adipose derived adult stem (hADAS) cells can differentiate into endothelial cells. METHODS: Stem cells were isolated and expanded from adipose tissue and then induced to differentiate into cells of osteogenic, adipogenic and neurogenic lineages in vitro. hADAS cells were induced with vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) to endothelial cells differentiation. hADAS cells were intravenously injected into mouse hindlimb ischemic models to test their ability to differentiate endothelial cells in vivo. RESULTS: hADAS cells were easily isolated and expanded in vitro. They had the ability to differentiate into osteogenic, adipogenic and neurogenic lineages. The cells expressed vascular endothelial growth factor receptor-2 (VEGFR-2, Flk1), and expressed endothelial markers when cultured with VEGF and bFGF. In response to local cues, hADAS cells in vivo differentiate into endothelial cells that contributed to neoangiogenesis in hindlimb ischemia models. CONCLUSIONS: Flk1+ hADAS cells have multipotential not only similar to bone marrow mesenchymal stem cells, but also exhibiting characteristics of endothelial progenitor cells. They may be a potential source of endothelial cells for cellular pro-angiogenic therapies.

Adipose Tissue↗

The POU factor Oct-25 regulates the Xvent-2B gene and counteracts terminal differentiation in Xenopus embryos.

The Xvent-2B promoter is regulated by a BMP-2/4-induced transcription complex comprising Smad signal transducers and specific transcription factors. Using a yeast one-hybrid screen we have found that Oct-25, a Xenopus POU domain protein related to mammalian Oct-3/4, binds as an additional factor to the Xvent-2B promoter. This interaction was further confirmed by both in vitro and in vivo analyses. The Oct-25 gene is mainly transcribed during blastula and gastrula stages in the newly forming ectodermal and mesodermal germ layers. Luciferase reporter gene assay demonstrated that Oct-25 stimulates transcription of the Xvent-2B gene. This stimulation depends on the Oct-25 binding site and the bone morphogenetic protein-responsive element. Furthermore, Oct-25 interacts in vitro with components of the Xvent-2B transcription complex, like Smad1/4 and Xvent-2. Overexpression of Oct-25 results in anterior/posterior truncations and lack of differentiation for neuroectoderm- and mesoderm-derived tissues including blood cells. This effect is consistent with an evolutionarily conserved role of class V POU factors in the maintenance of an undifferentiated cell state. In Xenopus, the molecular mechanism underlying this process might be coupled to the expression of Xvent proteins.

Animals↗

fgf17b, a novel member of Fgf family, helps patterning zebrafish embryos.

Fibroblast growth factors (Fgfs) play important roles in the pattern formation of early vertebrate embryos. We have identified a zebrafish ortholog of human FGF17, named fgf17b. The first phase of fgf17b expression occurs in the blastodermal margin of late blastulae and in the embryonic shield of early gastrulae. The second phase starts after the onset of segmentation, mainly in the presomitic mesoderm and newly formed somites. Injection of fgf17b mRNA into one-cell embryos induces expression of the mesodermal marker no tail (ntl) and rescues ntl expression suppressed by overexpression of lefty1 (lft1). Overexpression of fgf17b dorsalizes zebrafish gastrulae by enhancing expression of chordin (chd), which is an antagonist of the ventralizing signals BMPs. In addition, overexpression of fgf17b posteriorizes the neuroectoderm. Simultaneous knockdown of fgf17b and fgf8 with antisense morpholinos results in reduction of chd and ntl. Knockdown of fgf17b can alleviate inhibitory effect of ectopic expression of fgf3 on otx1. These data together suggest that Fgf17b plays a role in early embryonic patterning. We also demonstrate that fgf17b and fgf8 have stronger mesoderm inducting activity than fgf3, whereas fgf17b and fgf3 have stronger activity in posteriorizing the neuroectoderm than fgf8. Like fgf8, activation of fgf17b expression depends on Nodal signaling.

Animals↗

Detection of Treponema pallidum in skin lesions of secondary syphilis and characterization of the inflammatory infiltrate.

BACKGROUND: Syphilis is an ancient sexually transmitted disease. However, the pathogenesis of mucocutaneous lesions of secondary syphilis is not completely understood. METHODS: We analyzed the presence of Treponema pallidum in formalin-fixed, paraffin-embedded biopsy specimens from mucocutaneous lesions of secondary syphilis using highly sensitive nested polymerase chain reaction (PCR). The inflammatory infiltrates from the same specimens are also characterized using immunohistochemical methods. RESULTS AND CONCLUSIONS: Ten out of 24 (41.7%) specimens are T. pallidum positive using nested PCR, whereas none of them is T. pallidum positive using traditional silver staining. The presence of T. pallidum in the mucocutaneous lesions indicates that mucocutaneous lesions of secondary syphilis might be caused by direct T. pallidum invasion rather than by an allergic reaction. Furthermore, the majority of inflammatory infiltrating cells are CD45RO-positive T cells and CD68-positive macrophages, suggesting that cellular immunity plays an important role in the host reaction against T. pallidum infection in secondary syphilis.

Adult↗

Noninvasive carcinoma of the breast: angiogenesis and cell proliferation.

CONTEXT: Angiogenesis and the cell proliferation index can predict the prognosis of invasive breast carcinoma; however, little is known of their roles in noninvasive tumor. OBJECTIVE: To investigate the correlation of microvessel density and cell proliferation index with other histologic parameters (histologic type, nuclear grade, and mitotic count) in 65 cases of noninvasive carcinoma of the breast. DESIGN: Formalin-fixed, paraffin-embedded tissues from 65 cases of carcinoma in situ of the breast were immunostained with antibody against factor VIII antigen and proliferation-associated nuclear antigen MIB-1. The microvessel density was measured by counting the total number of microvessels around the carcinoma in situ per 10 low-power microscopic fields. The cell proliferation index was calculated by counting MIB-1-positive nuclei in 100 tumor cells. A chi2 test and Spearman rank correlation test were used for statistical analysis. RESULTS: The microvessel density and cell proliferation index of comedo-type, high-nuclear-grade ductal carcinomas in situ are significantly higher than those of either noncomedo type ductal carcinomas in situ or lobular carcinoma in situ (P <.001). CONCLUSIONS: Angiogenesis and the cell proliferation index are active biological processes and may be considered as markers to separate low- and high-risk patients with noninvasive breast carcinomas.

Adult↗

[The shh promoter of zebrafish directs the expression of GFP in notochord].

In vitro experiment showed that HNF3beta was the direct regulator of sonic hedgehog (shh) promoter. To investigate the activity of zebrafish shh promoter in vivo, we constructed the expression vector pShh-EGFP with ligating a 538 bp zebrafish shh promoter,which contained two HNF3beta binding sites, to EGFP. The pShh-EGFP DNA was microinjected into one-cell stage embryos of the zebrafish and the embryos were observed for GFP expression with fluorescent microscopy. GFP expression started during gastrulation in the axial hypoblast layer. During segmentation, GFP was detected in the notochord but not in the foor plate. Our experiment demonstrated that the 538 bp shh promoter containing two HNF3beta binding sites is able to confer the notochord-expressing activity.

Animals↗