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Biomedical subjects

Yan Geng

Publications and source records attributed to Yan Geng.

At least 19 recordsLinked to original sources
PubMed2007

Kinase-independent function of cyclin E.

E-type cyclins are thought to drive cell-cycle progression by activating cyclin-dependent kinases, primarily CDK2. We previously found that cyclin E-null cells failed to incorporate MCM helicase into DNA prereplication complex during G(0) --> S phase progression. We now report that a kinase-deficient cyclin E mutant can partially restore MCM loading and S phase entry in cyclin E-null cells. We found that cyclin E is loaded onto chromatin during G(0) --> S progression. In the absence of cyclin E, CDT1 is normally loaded onto chromatin, whereas MCM is not, indicating that cyclin E acts between CDT1 and MCM loading. We observed a physical association of cyclin E with CDT1 and with MCMs. We propose that cyclin E facilitates MCM loading in a kinase-independent fashion, through physical interaction with CDT1 and MCM. Our work indicates that-in addition to their function as CDK activators-E cyclins play kinase-independent functions in cell-cycle progression.

Animals↗
PubMed2006

In utero exposure to maternal diets containing soy protein isolate, but not genistein alone, protects young adult rat offspring from NMU-induced mammary tumorigenesis.

The linkage of nutrition and cancer prevention is an intriguing concept that is gaining widespread support. Here, we investigated the influence of developmental context on dietary protection against tumorigenesis initiated by the direct-acting carcinogen N-methyl-N-nitrosourea (NMU), and examined potential mechanisms underlying these effects. Rats were exposed only in utero or for lifetime to American Institute of Nutrition-93G diets made with casein (CAS), soy protein isolate (SPI) or CAS supplemented with genistein (GEN). Mammary glands of post-natal day (PND) 50 rats prior to NMU administration were examined for apoptotic status, pro-apoptotic gene expression and immunoreactive phosphatase and tensin homolog deleted on chromosome ten (PTEN) and epithelial cadherin (E-cadherin) levels, whereas mammary tumor parameters were evaluated 99 days post-NMU. Animals exposed only in utero to SPI had increased tumor latency, decreased tumor multiplicity and lower higher grade tumors, than those fed CAS. In utero exposure to GEN resulted in similar tumor parameters as the CAS group, whereas lifetime SPI exposure decreased tumor incidence that was not mimicked by in utero exposure alone. Mammary glands of PND50 rats fed lifetime SPI had increased terminal end bud apoptotic status and PTEN expression, than the other diet groups. Rats exposed only in utero to SPI or GEN had higher membrane E-cadherin in mammary structures than those lifetime-fed CAS or SPI. Thus, limited exposure during gestation to SPI can positively influence resistance to chemically induced mammary tumorigenesis later in life. Preventative strategies against mammary and other types of cancer might be uncovered by refinement of the developmental window for dietary factor exposure.

Animals↗
PubMed2006

Essential role for cyclin D3 in granulocyte colony-stimulating factor-driven expansion of neutrophil granulocytes.

The proliferation of neutrophil granulocyte lineage is driven largely by granulocyte colony-stimulating factor (G-CSF) acting via the G-CSF receptors. In this study, we show that mice lacking cyclin D3, a component of the core cell cycle machinery, are refractory to stimulation by the G-CSF. Consequently, cyclin D3-null mice display deficient maturation of granulocytes in the bone marrow and have reduced levels of neutrophil granulocytes in their peripheral blood. The mutant mice are unable to mount a normal response to bacterial challenge and succumb to microbial infections. In contrast, the expansion of hematopoietic stem cells and lineage-committed myeloid progenitors proceeds relatively normally in mice lacking cyclin D3, revealing that the requirement for cyclin D3 function operates at later stages of neutrophil development. Importantly, we verified that this requirement is specific to cyclin D3, as mice lacking other G(1) cyclins (D1, D2, E1, or E2) display normal granulocyte counts. Our analyses revealed that in the bone marrow cells of wild-type mice, activation of the G-CSF receptor leads to upregulation of cyclin D3. Collectively, these results demonstrate that cyclin D3 is an essential cell cycle recipient of G-CSF signaling, and they provide a molecular link of how G-CSF-dependent signaling triggers cell proliferation.

Animals↗
PubMed2006

Electric field manipulation of charged copolymer worm micelles.

Manipulation of diblock copolymer worm micelles by external electric fields is visualized by fluorescence microscopy in dilute, aqueous solution. Hydrodynamic coupling of the poly(acrylic acid)-(1,4)-polybutadiene (PAA-PBD) worm motion to the electric field and the effective stiffening of the worms in an oscillating electric field are demonstrated. A brief discussion on using this technique to estimate the rheological properties of wormlike micelles is presented.

Butadienes↗
PubMed2006

Specific ion pairing and interfacial hydration as controlling factors in gemini micelle morphology. Chemical trapping studies.

Results from chemical trapping experiments in micellar solutions containing 1.5-5 mM aqueous solutions of three didodecyl dicationic dibromide gemini surfactants with different methylene spacer lengths (12-n-12 2Br where n = 2-4 CH(2) groups) gave quantitative estimates of the molarities of interfacial bromide (Br(m)) and water (H(2)O(m)), the fractions of free and paired headgroups and counterions, and the net headgroup charge. These results are one of the most detailed compositional studies of an association colloid interface to date. Br(m) increases and H(2)O(m) decreases as n decreases and the two cationic charges are closer together. The 12-2-12 2Br gemini (the only one of the three geminis known to form threadlike micelles) shows a marked increase in Br(m) (from 2.3 to 3.6 M) and a decrease in H(2)O(m) (from 35 to 17 M) at the exceptionally low surfactant concentration in the vicinity of the previously reported sphere-to-rod transition or second cmc concentration. Rod formation occurs because of an increase in headgroup-counterion association and dehydration at the micelle surface that depend on both the free energies of hydration and specific ion interactions and surfactant and counterion concentrations. These and other recent chemical trapping results support a new model for the balance of forces controlling morphological transitions of association colloids. The hydrophobic effect drives the formation of headgroup-counterion pairs, which have a lower demand for water of hydration. Release of water permits tighter packing and formation of cylindrical aggregates.

Journal Article↗
PubMed2006

Requirement for CDK4 kinase function in breast cancer.

Cyclin D1 is overexpressed in the majority of human breast cancers. We previously found that mice lacking cyclin D1 are resistant to mammary carcinomas triggered by the ErbB-2 oncogene. In this study, we investigated which function of cyclin D1 is required for ErbB-2-driven mammary oncogenesis. We report that the ability of cyclin D1 to activate cyclin-dependent kinase CDK4 underlies the critical role for cyclin D1 in breast cancer formation. We also found that the continued presence of CDK4-associated kinase activity is required to maintain breast tumorigenesis. We analyzed primary human breast cancers and found high cyclin D1 levels in a subset (approximately 25%) of ErbB-2-overexpressing tumors. We propose that this subset of breast cancer patients might benefit from inhibiting CDK4 kinase.

Animals↗
PubMed2006

Tp53-associated growth arrest and DNA damage repair gene expression is attenuated in mammary epithelial cells of rats fed whey proteins.

Dietary protection from mammary cancer is likely coordinated through multiple signaling pathways, based on the known heterogeneity of the disease and the distinct origins of mammary tumor cells. The present study examined the modulatory effects of dietary intake of whey protein hydrolysate (WPH) relative to casein (CAS), on mammary epithelial cell resistance to endogenous DNA damage using Tp53 gene expression and signaling as a read-out, and on systemic proapoptotic and immune surveillance activity, in young adult female Sprague-Dawley rats. Rats were fed AIN-93G diets made with CAS or WPH as the sole protein source beginning at gestation d 4. At postnatal day (PND) 50, mammary glands of rats fed WPH had lower levels of activated Tp53 and p38 mitogen-activated protein kinase proteins, and reduced transcript levels for Tp53-associated DNA damage repair, growth arrest, and proapoptotic genes than those of CAS-fed rats. Serum from WPH-fed rats had greater apoptotic activity in MCF-7 tumor cells than that from rats fed CAS. Serum levels of monocyte chemoattractant protein (MCP)-1 were higher in WPH- than in CAS-fed rats. MCF-7 cells treated with CAS serum + recombinant rat MCP-1 had apoptotic activity and Tp53 and p21 gene expression levels comparable to those treated with WPH serum or recombinant MCP-1. Results indicate that mammary glands of rats fed a WPH diet are more protected from endogenous DNA damage than are those of CAS-fed rats, and identify MCP-1 as a potential serum biomarker for the positive effects of healthy diets.

Administration, Oral↗
PubMed2006

[Investigation of relationship between prehospital care for traumatic shock and postoperative acute lung injury/acute respiratory distress syndrome].

OBJECTIVE: To investigate and analyze the correlation and clinical significance of prehospital treatment for traumatic shock and postoperative acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). METHODS: Six hundred cases in the last 10 years were enrolled for double-blind randomized control study. They were divided into 3 groups. Group A consisted of 184 cases who had received combined treatment, group B consisted of 305 cases who had received fluid replacement only and group C consisted of 111 cases with no treatment. The incidence of systemic inflammatory response syndrome (SIRS), ALI and ARDS of each group were analyzed and compared. SIRS was graded at 1 (T0) after admission, 24 (T1), 48 (T2), 96 (T3) and 144 hours (T4) after operation. RESULTS: In 524 cases diagnosis of SIRS was made among 600 patients (87.33%). Among them 73.37% (135/184 cases) were in group A, 91.48% (279/305 cases) belonged to group B and 99.10% (110/111 cases) in group C. The scores of SIRS were notably lower in group A than B and C at each time point (all P<0.01), and they were lower in group B than those in group C (all P<0.01), they recovered at T3 after operation in group A while in group B patients recovered at 144 hours after operation. Eleven patients among 184 (5.98%) were diagnosed to have ALI including 1 case progressed to ARDS and 1 case to MODS and no one died, while in group B 32 cases in 305 (10.49%) had ALI with 7 cases progressed to ARDS and 3 cases to MODS while 3 deaths and in group C 23 among 111 (20.72%) had ALI, and 8 patients progressed to ARDS, 5 cases to MODS and 5 deaths. CONCLUSION: Prehospital treatment is closely related with postoperative ALI, and combined treatment is beneficial in reducing the incidence of postoperative ALI/ARDS.

Adult↗
PubMed2006

[Design and implementation of an intellectualized measuring instrument for medical electricity security parameters].

An introduction of an intelligent testing instrument for medical electrical equipment security is given in this article. The realization of its testing functions is based on a single-chip processor, the high-voltage control circuit and the relay combination network technology. It can be used to test security parameters such as the continuous leakage current, patient auxiliary current, dielectric strength and protective earth impedance. It is suitable for the medical electricity security testing of Kind I, II and Type B, BF, CF (internal power supply) medical electrical equipments.

Electricity↗
PubMed2005

Ion pair formation in water. association constants of bolaform, bisquaternary ammonium, electrolytes by chemical trapping.

The first and second association constants, K1 and K2, for ion pair formation in aqueous 0.02-3.5 M solutions of bis(trimethyl)-alpha,omega-alkanediammonium halides with variable spacer lengths, 1-n-1 2X (n = 2-4, X = Cl, Br) and bolaform salts and for tetramethylammonium halides (TMAX, X = Cl, Br), K(TMAX), were determined by the chemical trapping method. Values for K(TMAX) are small, K(TMABr) = 0.83 M(-1) and K(TMACl) = 0.29 M(-1), in agreement with literature values. For the bolaform salts, K1 depends on spacer length and counterion type, ranges from 0.4 to 17 M(-1), is 2-10 times larger than K2, is larger for Br- than Cl-, and decreases by a factor of approximately 3 for Cl- and approximately 10 for Br- as n increases from 2 to 4. K2, for the formation of bolaform dihalide pair, is essentially the same as that for ion pair formation in TMAX solutions, i.e., K2 approximately K(TMAX). Values of K1 and K(TMABr) obtained from changes in 79Br line widths are in good agreement with those obtained by chemical trapping. The results are consistent with a thermodynamic model in which the ion association depends on the balance of the ion specific hydration free energies of cations and anions and their ion specific and hydration interactions in ion pairs. Spacer length dependent ion pairing by bolaform electrolytes, which are analogues of the headgroups and counterions of gemini amphiphiles, suggests a new model for the spacer length dependent sphere-to-rod transitions of gemini micelles. Neutral, but polar, headgroup-counterion pairs have a lower demand for hydration that free headgroups and counterions, and headgroup-counterion pair formation releases interfacial water into the bulk aqueous phase, permitting tighter amphiphile packing in rodlike micelles.

Electrolytes↗
PubMed2005

Hydrolytic degradation of poly(ethylene oxide)-block-polycaprolactone worm micelles.

Spherical micelles and nanoparticles made with degradable polymers have been of great interest for therapeutic application, but degradation-induced changes in a spherical morphology can be subtle and mechanism/kinetics appears poorly understood. Here, we report the first preparation of giant and flexible worm micelles self-assembled from degradable copolymer poly(ethylene oxide)-block-polycaprolactone. Such worm micelles spontaneously shorten to generate spherical micelles, triggered by polycaprolactone hydrolysis, with distinct mechanism and kinetics from that which occurs in bulk material.

Hydrolysis↗
PubMed2005

Null mutation of Kruppel-like factor9/basic transcription element binding protein-1 alters peri-implantation uterine development in mice.

Female mice null for the basic transcription element binding protein-1 (Bteb1) gene have reduced numbers of implanting embryos. We hypothesized that the implantation defect, resulting in subfertility, is a consequence of developmental asynchrony between the embryo and uterine endometrium at peri-implantation. To address this, endometrium from wild-type (WT) and Bteb1(-/-) females at 0.5 to 5.5 days postcoitum (dpc) were evaluated for proliferation (BrdU labeling), apoptosis (TUNEL), and steroid hormone receptor expression (immunohistochemistry). Loss of BTEB1 did not affect serum estrogen (E) and progesterone (P) levels. In stroma (ST), the numbers of progesterone receptor (PGR) and HomeoboxA10 (HOXA10)-expressing cells were lower (3.5 and 4.5 dpc), while those of estrogen receptor-alpha (ESR1) were higher (3.5 dpc), with Bteb1 ablation. The peak of proliferation in luminal epithelium (LE), glandular epithelium (GE), and ST was delayed, while the apoptotic index in all cell types was increased (2.5 dpc) in Bteb1(-/-) relative to WT mice. The numbers of PGR-positive ST cells was negatively correlated with LE proliferation in WT mice; this correlation was lost in Bteb1(-/-) mice and was not observed before 2.5 dpc for both genotypes. Proliferation and apoptosis in all endometrial compartments, as well as the numbers of PGR-, HOXA10-, and ESR1-expressing ST cells, were lower in Bteb1(-/-) relative to WT mice after ovariectomy and E + P treatment. Results suggest that BTEB1, by regulating ST PGR expression and transactivation, participates in the paracrine control of LE proliferation by PGR and thus is important for establishment of a receptive uterus critical for successful implantation.

Animals↗
PubMed2005

The soy isoflavone genistein promotes apoptosis in mammary epithelial cells by inducing the tumor suppressor PTEN.

The isoflavone genistein (GEN), a biologically active component of soy foods, is associated with reduced breast cancer risk in women who consume soy-rich diets. GEN has been reported to influence many biological processes, of which suppression of cell proliferation and stimulation of apoptosis are considered to be the major pathways underlying its inhibition of tumorigenesis. This study evaluated the mechanism by which diets containing GEN promote mammary epithelial cell death. We report that mammary glands of young adult female rats exposed from gestation day 4 to postnatal day 50, to AIN-93G diets containing as sole protein source, casein (CAS) supplemented with GEN, or soy protein isolate (SPI+) had increased apoptosis, relative to rats fed CAS diet devoid of GEN. Mammary gland proliferation was unaffected by diet. The increased apoptotic index in mammary glands of GEN and SPI+ rats was accompanied by increased levels of the tumor suppressor protein PTEN (phosphatase and tensin homolog deleted in chromosome ten), albeit enhanced mammary expression of the pro-apoptotic p21, Bax and Bok genes was observed only in GEN-fed rats. GEN-induced apoptosis in MCF-7 cells was concomitant with increased PTEN expression, and this was abrogated by PTEN siRNA. MCF-7 cells treated with serum from GEN- or SPI(+)-fed rats had increased apoptosis as well as increased levels of the PTEN transcript. PTEN siRNA attenuated the increased apoptotic response of MCF-7 cells to serum from rats fed SPI+ or GEN, although the inhibition to basal (CAS serum) apoptotic levels was achieved only for cells treated with GEN serum. Decreased p21 and Bok gene expression accompanied the inhibition of apoptosis by PTEN siRNA. Data implicate PTEN in the induction of apoptosis by GEN and suggest that the promotion of apoptosis leading to inhibition of tumorigenesis in vivo by diets containing GEN may also involve the distinct activities of yet unknown GEN metabolite(s) and/or other systemic factors induced by GEN.

Animals↗
PubMed2005

Organometallic silver(I) supramolecular complexes generated from multidentate furan-containing symmetric and unsymmetric fulvene ligands and silver(I) salts.

One new conjugated symmetric fulvene ligand L1 and two new unsymmetric fulvene ligands L2 and L3 were synthesized. Five new supramolecular complexes, namely Ag2(L1)3(SO3CF3)3 (1) (1, monoclinic, P2(1)/c; a = 12.702(3) A, b = 26.118(7) A, c = 13.998(4) A, beta = 96.063(4) degrees, Z = 4), [Ag(L1)]ClO4 (2) (monoclinic, C2/c; a = 17.363(2) A, b = 13.2794(18) A, c = 13.4884(18) A, beta = 100.292(2) degrees, Z = 8), [Ag(L1)(C6H6)SbF6] x 0.5C6H6 x H2O (3) (monoclinic, P2(1)/c; a = 6.8839(11) A, b = 20.242(3) A, c = 18.934(3) A, beta = 91.994(3) degrees, Z = 4), Ag(L2)(SO3CF3) (4) (triclinic, P1; a = 8.629(3) A, b = 10.915(3) A, c = 11.178(3) A, alpha = 100.978(4) degrees, beta = 91.994(3) degrees, gamma = 105.652(4) degrees, Z = 2), and Ag(L3)(H2O)(SO3CF3) (5) (triclinic, P1; a = 8.914(5) A, b = 10.809(6) A, c = 11.283(6) A, alpha = 69.255(8) degrees, beta = 87.163(9) degrees, gamma = 84.993(8) degrees, Z = 2) were obtained through self-assembly based on these three new fulvene ligands in a benzene/toluene mixed-solvent system. Compounds 1-5 have been fully characterized by infrared spectroscopy, elemental analysis, and single-crystal X-ray diffraction. The results indicate that the coordination chemistry of new fulvene ligands is versatile. They can adopt either cis- or trans-conformation to bind soft acid Ag(I) ion through not only the terminal -CN and furan functional groups but also the fulvene carbon atoms into organometallic coordination polymers or discrete complexes. In addition, the luminescent properties of L1-L3 and their Ag(I) complexes were investigated preliminarily in EtOH and solid state.

Journal Article↗
PubMed2005

Visualizing worm micelle dynamics and phase transitions of a charged diblock copolymer in water.

Assemblies of block copolymer amphiphiles are sometimes viewed as glassy, frozen, or static colloids, especially in strongly segregating solutions. Here, we visualize by fluorescence microscopy and AFM the dynamics and transitions of single cylindrical micelles and vesicles composed of a charged diblock copolymer in water. In mapping the salt- and pH-dependent phase diagrams of a near-symmetric diblock of poly(acrylic acid)-polybutadiene, low pH and high salt (NaCl, CaCl2) neutralize and screen the charged corona sufficiently to foster membrane formation and generate vesicles. Decreased salt and neutral pH increases intra-coronal repulsion and drives a transition to multi-branched cylinders and highly stable, but fluid and flexible, worm micelles. Ca2+ both stiffens cylinders and stabilizes them relative to spheres. Further increase of intra-coronal repulsion generates spherical micelles by fragmentation and pinch-off at the ends of worms. Both the transition kinetics and phase diagrams indicate divalent cation is about 5-10-fold more effective than monovalent in stabilizing all nonspherical morphologies.

Hydrogen-Ion Concentration↗
PubMed2005

Origin of the sphere-to-rod transition in cationic micelles with aromatic counterions: specific ion hydration in the interfacial region matters.

Sphere-to-rod transitions of cetyltrimethylammonium (CTA+) micelles with dichlorobenzoate counterions are remarkably substituent dependent. Simultaneous estimates of the interfacial molarities of H2O, MeOH, and Cl- and 2,6- and 3,5-dichlorobenzoate (2,6OBz and 3,5OBz) counterions were obtained by the chemical trapping method in mixed micelles of CTACl/CTA3,5OBz and CTACl/CTA2,6OBz without added salt. Increasing the CTA3,5OBz mole fraction produces a marked concurrent increase in interfacial 3,5OBz- and a decrease in interfacial H2O concentrations through the sphere-to-rod transition. No abrupt concentration changes are observed with increasing CTA2,6OBz mole fraction. Counterion-specific changes in the interfacial water concentration may be a major contributor to the delicate balance of forces governing micellar morphology.

Journal Article↗
PubMed2005

Uterine phenotype of young adult rats exposed to dietary soy or genistein during development.

Dietary soy intake is associated with protection from breast cancer, but questions persist on the potential risks of the major soy isoflavone genistein (GEN) on female reproductive health. Here, we evaluated intermediate markers of cancer risk in uteri of cycling, young adult Sprague-Dawley rats lifetime exposed to one of three AIN-93G semipurified diets: casein (CAS), soy protein isolate (SPI+ with 276 mg GEN aglycone equivalents/kg) and CAS+GEN (GEN at 250 mg/kg). Postnatal day 50 (PND50) rats lifetime exposed to GEN or SPI+ had similar uterine luminal epithelium height, myometrial thickness, endometrial gland numbers, endometrial immunoreactive proliferating cell nuclear antigen (PCNA), and serum estrogen and progesterone, as CAS-fed rats. GEN-fed rats showed modestly increased apoptosis in uterine glandular epithelium, compared to those of CAS- or SPI+-fed groups. Diet had no effect on the uterine expression of genes for the tumor suppressors PTEN, p53 and p21, and the apoptotic-associated proteins Bcl2, Bax and progesterone receptor. Uterine tissue and serum concentrations of total GEN were higher in rats fed GEN than in those fed SPI+. Human Ishikawa endocarcinoma cells treated with GEN-fed rat serum tended to exhibit increased apoptotic status than those treated with CAS-fed rat serum. Exogenously added GEN (0.2 and 2 microM) increased, while estradiol-17beta (0.1 microM) decreased Ishikawa cell apoptosis, relative to untreated cells. Results suggest that lifetime dietary exposure to soy foods does not alter uterine cell phenotype in young adult rats, while GEN, by enhancing uterine endometrial glandular apoptosis in vivo and in vitro, may confer protection against uterine carcinoma. Given its limited influence on uterine phenotype of young adult females, GEN, when taken as part of soy foods or as supplement, should be favorably considered for other potential health benefits.

Animals↗