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Biomedical subjects

Lin Yang

Publications and source records attributed to Lin Yang.

At least 145 records · Page 8Linked to original sources

Isomeric distribution of conjugated linoleic acids (CLA) in the tissues of layer hens fed a CLA diet.

The isomeric distribution of conjugated linoleic acids (CLA) in the tissue lipids of hens in relation to that in the diet was examined. Silver-ion high-performance liquid chromatography was used to quantify individual CLA isomers in total tissue lipids, phospholipids, and triacylglycerols. It was found that the deposition of CLA isomers in hen tissues was selective. All tissues including serum, liver, heart, kidney, abdominal fat, and leg and breast muscles had lesser amounts of total cis/trans isomers ranging from 75.87 to 89.13% of total CLA, which was in contrast to the value of 92% of total CLA in the dietary lipids. Total trans/trans isomers in all tissue lipids ranging from 6.11 to 18.02% of total CLA were greater than that in the diet (4.19%). Among the individual trans/trans isomers, all tissues except for adipose tissue and brain incorporated greater amounts of t-12,t-14-18:2, t-11,t-13-18:2,t-10,t-12-18:2, t-9,t-11-18:2, and t-18,t-10-18:2 compared with the values of the diet. Within the cis/trans group, lesser amounts of c-10,t-12/t-10,c-12-18:2 were found to incorporate into all tissues compared with the value of the diet. Serum and liver had higher percentages of c-9,t-11/t-9,c-11, whereas the other tissues had similar levels of this isomer compared with that of the diet. It was also observed that supplementation of CLA in the diet of layer hens decreased the concentration of docosahexaenoic acid (22:6n-3) in all of the tissue lipids. It is concluded that dietary CLA can transfer to the tissue but that incorporation of CLA isomers into the tissue is selective in hens.

Animals↗

Activation of phosphatidylinositol 3-kinase/Akt pathway by androgen through interaction of p85alpha, androgen receptor, and Src.

Recent studies have demonstrated that the cell growth and antiapoptotic actions of androgen could be dissociated from the transcriptional activity of the receptor and were, instead, mediated by activation of a mitogen-activated protein kinase pathway. This finding suggests an important cellular function of androgen receptor (AR) outside the nucleus. In this report, we demonstrate that androgen activates phosphatidylinositol 3-kinase (PI3K) and Akt, including AKT1 and AKT2, in AR-positive cells. Androgen-induced cell growth and survival were inhibited by PI3K inhibitor and dominant-negative Akt. AR interacts with the p85alpha regulatory subunit of PI3K, and its binding affinity is increased after androgen stimulation. The sites of interaction on the two proteins were mapped to the C-terminal Src-homology 2 domain of p85alpha and N terminus of AR. Activation of PI3K/Akt by androgen was inhibited by dominant-negative Src. Neither N-terminal truncated nor proline-rich region-deleted AR mutants, which are unable to bind to p85alpha and Src, respectively, was able to mediate androgen-induced PI3K/Akt activation. AR with deletion of C-terminal region including ligand binding domain, however, retains the ability to activate PI3K/Akt upon androgen stimulation, which supports the notion that nongenomic function of androgen is mediated by its interaction with membrane receptors (1, 3, 4). These findings indicate that a triple complex between AR, p85alpha, and Src is required for androgen-stimulated PI3K/Akt activation, and that the PI3K/Akt pathway, in addition to mitogen-activated protein kinase, mediates androgen-induced cell growth and cell survival.

Apoptosis↗

New phases of phospholipids and implications to the membrane fusion problem.

Membrane fusion is a ubiquitous process in eukaryotic cells. When two membranes fuse, lipid must undergo molecular rearrangements at the point of merging. To understand how lipid structure transitions occur, scientists studied the phase transition of lipid between the lamellar (L(alpha)) phase and the inverted hexagonal (H(II)) phase, based on the idea that lipid must undergo a similar rearrangement as in fusion. However, previous investigations on the system of dioleoylphosphatidylcholine (DOPC) and dioleoylphosphatidylethanolamine (DOPE) did not reveal intermediate phases between the L(alpha) and H(II) phases. Recently, we found a rhombohedral phase of diphytanoylphosphatidylcholine between its L(alpha) and H(II) phases using substrate-supported samples. Here we report the observation of two new phases in the DOPC-DOPE system: a rhombohedral phase and a distorted hexagonal phase. The rhombohedral phase confirms the stalk hypothesis for the L(alpha)-H(II) transition, but the phase of stable stalks exists only for a certain range of spontaneous curvature. The distorted hexagonal phase exists only in a lipid mixture. It implies that lipids may demix to adjust its local spontaneous curvature in order to achieve energy minimum under stress.

Chemistry, Physical↗

Interleukin-6 differentially regulates androgen receptor transactivation via PI3K-Akt, STAT3, and MAPK, three distinct signal pathways in prostate cancer cells.

The effects of IL-6 on prostate cancer cells are well documented yet remain controversial. Some reports suggested that IL-6 could promote prostate cancer cell growth, while others showed that IL-6 could repress prostate cancer cell growth. Here, we systemically examined various IL-6 signaling pathways in prostate cancer cells and found that IL-6 could go through at least three distinct pathways to modulate the functions of androgen receptor (AR), a key transcriptional factor to control the prostate cancer growth. Our results show that IL-6 can enhance AR transactivation via either the STAT3 or MAPK pathways. In contrast, IL-6 can suppress AR transactivation via the PI3K-Akt pathway. Co-existence of these various signaling pathways may result in either additive or conflicting effects on AR transactivation. Together, our results indicate that the balance of these various pathways may then determine the overall effect of IL-6 on AR transactivation.

DNA-Binding Proteins↗

RelA control of IkappaBalpha phosphorylation: a positive feedback loop for high affinity NF-kappaB complexes.

NF-kappaB-IkappaB complex formation regulates the level and specificity of NF-kappaB activity. Quantitative analyses showed that RelA-NF-kappaB-induced IkappaBalpha binding is regulated through inhibitor retention and phosphorylation. RelA caused an increase in IkappaBalpha phosphorylation and in degradation, which was enhanced monotonically with inhibitor concentration. In vivo analysis demonstrated the RelA-induced IkappaBalpha/RelA interactions to be specific, saturable, and phosphorylation-dependent. In addition, it showed that phosphorylation regulates both the level and affinity of the complexes and demonstrated an increased average affinity to coincide with reduction in the level of complexes during cytokine-induced pathway activation. The data show that RelA regulation of NF-kappaB-IkappaBalpha complex formation is IkappaBalpha phosphorylation-dependent and that IkappaBalpha/NF-kappaB binding is dynamic and determined by concentration of the subunits. In addition, they suggest that regulation of both complex levels and affinities through phosphorylation, with effects on the system steady state, participate in selective activation of the NF-kappaB pathway.

Fibroblasts↗

APPL suppresses androgen receptor transactivation via potentiating Akt activity.

APPL may function as an adapter protein to modulate the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Although we have previously proven that the PI3K/Akt pathway can suppress androgen receptor (AR) transactivation, the potential linkage from APPL to the AR remains unclear. Here we demonstrated that APPL could suppress AR-mediated transactivation in a dose-dependent manner in LNCaP and PC-3 cells. This suppressive effect could be blocked by either dominant-negative Akt or dominant-negative PI3K or LY294002, suggesting that the APPL-mediated suppression of AR transactivation is dependent on the PI3K/Akt pathway. We also observed that APPL could further enhance the Akt-mediated suppression of AR transactivation and AR target gene using the reporter gene and Northern blot assay. APPL was able to enhance insulin-like growth factor (IGF-1)-mediated Akt activation. The abrogation of IGF-1-mediated Akt activation by the dominant-negative PI3K or LY294002 or antisense APPL suggests that APPL may function as an important adapter protein in controlling the IGF-1 --> Akt signal pathway. Co-immunoprecipitation and glutathione S-transferase pull-down assays suggest that APPL, Akt, and AR may exist in a complex and Akt may serve as an important bridge factor for the association of APPL with AR. Together, our data indicate that APPL may suppress AR transactivation via potentiating Akt activity.

Animals↗

Cooperativity between pepsin and crystallization of calcium carbonate in distilled water.

Cooperativity between pepsin and crystallization of calcium carbonate in distilled water was studied. The results show that vaterite was formed under the influence of pepsin and the crystalline product was a composite of vaterite and pepsin. The component of this material was similar to that of nacre. At the same time, the crystallization of calcium carbonate had also an important effect on the secondary structure of the pepsin. The secondary structure of the pepsin was characterized through FT-IR technology. The result indicated that the pure pepsin is composed of 24.38% alpha-helices, 29.91% beta-sheets, 39.32% beta-turns and 6.49% random structures and the pepsin in the CaCO(3)-pepsin solution is composed of 2.09% alpha-helices, 93.304% beta-sheets, 4.592% beta-turns and 0.006% random structure. During the crystallization of the calcium carbonate from the pepsin solution, the secondary structure of the pepsin transformed. These results showed that there was cooperativity between the crystallization of vaterite and the pepsin. The cooperative mechanism is discussed.

Calcification, Physiologic↗

A rhombohedral phase of lipid containing a membrane fusion intermediate structure.

We constructed the electron density distribution from the x-ray diffraction of a phase of phospholipid that exhibited rhombohedral symmetry. To determine the phases of the diffraction amplitudes, we first extended the well-known one-dimensional swelling method for planar bilayers to a three-dimensional method applicable to a layered system containing in-plane structures, such as rhombohedral structures. The complete phase determination was accomplished by a combination of the swelling method and Luzzati's pattern recognition method. The constructed electron density distribution showed that in each unit cell, two apposed monolayers merged across the water layer and developed into an hourglass structure consistent with a postulated membrane fusion intermediate state called a stalk. The observation of the stalk structure lends a strong support to the stalk hypothesis for membrane fusion and opens a way to measure the structural parameters in the fusion pathway.

Electrons↗

Tissue engineered cartilage generated from human trachea using DegraPol scaffold.

OBJECTIVE: To date numerous attempts have been undertaken to conquer the challenging problem of reconstructing long segmental tracheal defects, as yet without lasting success. Recently, employing concepts of tissue engineering in animals, cartilage-like constructs were transplanted in vivo. However, both the feasibility of fabricating tracheal replacements and the use of human tracheal chondrocytes (HTC) for tissue engineering are still under investigation. In this study, we optimized isolation and cultivation techniques for human tracheal cartilage, assessing the feasibility of seeding these cells onto a novel, three-dimensional (3-D) polyester-urethane polymer (DegraPol). METHODS: Human tracheal cartilage was harvested from the trachea of lung donors, digested in 0.3% collagenase II, and the condrocytes serially passaged every 7-9 days. Cells were also cultivated over agar plate during the total 6-8 weeks expansion phase. Thereafter, chondrocytes were seeded onto DegraPol (pore sizes 150-200 microm) with a seeding density of 2.4 x 10(7)/ml, and chondrocyte-polymer constructs maintained during in vitro static culture. RESULTS: HTC displayed stable proliferation kinetics in monolayer culture with positive expression of collagen type II. Following polymer seeding, both cellular proliferation and extracellular matrix (ECM) production, as measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and glycosaminoglycan assays, continued over extended culture. Active growth of HTC on DegraPol was further demonstrated by Alcian blue staining, with the histomorphological appearance of the construct resembling that of native cartilage. Scanning electron microscopy showed chondrocyte growth and ECM synthesis both on the surface and inside the porous scaffold, with a dense cell layer on the surface of the scaffold and a lower cell distribution in the scaffold's interior. CONCLUSIONS: The harvested chondrocytes from human trachea cartilage expand well in vitro and possess the ability to form new cartilage-like tissue when seeded onto DegraPol matrix. However, improved culture conditions are needed to permit cellular growth throughout cell-polymer constructs.

Absorbable Implants↗

Synthesis, characterization, and antibacterial activities of some rare Earth metal complexes of pipemidic acid.

Eight new solid complexes of pipemidic acid (PPA) with trichlorizated rare earth metals LaCl(3), CeCl(3), PrCl(3), NdCl(3), SmCl(3), TbCl(3), DyCl(3), and YCl(3) have been synthesized. The complexes were characterized by elemental analyses, IR, NMR, and molar conductance measurements. The general formulas of the complexes are [M(PPA)(4)]Cl(3) (M=Ce(III), Pr(III), Nd(III), Sm(III), Tb(III), Dy(III), Y(III)), and [La(PPA)(4)Cl]Cl(2). At the same time, the antibacterial activities of PPA and four of its complexes were tested. The results show that PPA and its complexes all have inhibitory action against bacteria of Escherichia coli, Bacillus subtilis, Streptococcus pneumoniae, and Pseudomonas aeruginosa but not Staphylococcus aureus. We compared their antibacterial activities and found that the antibacterial activity of [La(PPA)(4)Cl]Cl(2) against S. pneumoniae is much stronger than that of PPA and the other complexes.

Anti-Infective Agents↗

PTEN encoding product: a marker for tumorigenesis and progression of gastric carcinoma.

AIM: To detect the expression of PTEN encoding product in normal mucosa, intestinal metaplasia (IM), dysplasia and carcinoma of the stomach, and to investigate its clinical implication in tumorigenesis and progression of gastric carcinoma. METHODS: Formalin-fixed paraffin embedded specimens from 184 cases of gastric carcinoma, their adjacent normal mucosa, IM and dysplasia were evaluated for PTEN protein expression by SABC immunohistochemistry. PTEN expression was compared with tumor stage, lymph node metastasis, Lauren's and WHO's histological classification of gastric carcinoma. Expression of VEGF was also detected in 60 cases of gastric carcinoma and its correlation with PTEN was concerned. RESULTS: The positive rates of PTEN protein were 100 %(102/102), 98.5 %(65/66), 66.7 % (4/6) and 47.8 %(88/184) in normal mucosa, IM, dysplasia and carcinoma of the stomach, respectively. The positive rates in dysplasia and carcinoma were lower than in normal mucosa and IM (P<0.01). Advanced gastric cancers expressed less frequent PTEN than early gastric cancer (42.9 % vs 67.6 %, P<0.01). The positive rate of PTEN protein was lower in gastric cancer with than without lymph node metastasis (40.3 % vs 63.3 %, P<0.01). PTEN was less expressed in diffuse-type than in intestinal-type gastric cancer (41.5 % vs 57.8 %, P<0.05). Signet ring cell carcinoma showed the expression of PTEN at the lowest level (25.0 %, 7/28); less than well and moderately differentiated ones (P<0.01). Expression of PTEN was not correlated with expression of VEGF (P>0.05). CONCLUSION: Loss or reduced expression of PTEN protein occures commonly in tumorigenesis and progression of gastric carcinoma. It is suggested that PTEN can be an objective marker for pathologically biological behaviors of gastric carcinoma.

Biomarkers, Tumor↗

[High expression of LIP1 in Pichia pastoris].

The gene of LIP1, the most important isoenzyme of Candida rugosa lipase (CRL), was artificially synthesized according to its mature peptide sequence. It consisted of 20 codons of preference in Pichia pastoris. The artificial gene was cloned into methanol-inducible expression vector pPICZalphaA, and constitutive expression vector pGAPZalphaA, respectively. The linearized recombinant plasmids were transformed into chromosome of Pichia pastoris SMD1168H strain by electroporation. The abilities of expressing LIP1 in both transformed yeasts had been compared, and the yeast transformed with pGAPZalphaA was more efficient than pPICZalphaA. A recombinant yeast strain named CHT-II expressed LIP1 constitutively, and was the most efficient one. Some enzymatic properties of the recombinant LIP1 were also determined. CHT-II secreted LIP1 into supernate at a level of 2.00x10(5) u/L after 72 h (the cells had been transferred to fresh culture medium at the 24th h). After optimizing the conditions for high cell-density fermentation, the selected yeast strain could secrete LIP1 into supernate at a level of 1.395x10(6) u/L after 72 h. The results indicated that this modification of lip1 gene was successful.

Amino Acid Sequence↗

[Expression of PTEN-encoding product in different stages of carcinogenesis and progression of gastric carcinoma].

OBJECTIVE: To illustrate the significance of expression of phosphatase and tensin homologue derived from chromosome ten (PTEN) encoding product in normal mucosa, intestinal metaplasia (IM), dysplasia and carcinoma of the stomach, and to evaluate its clinical implication in tumorigenesis and progression of gastric carcinoma. METHODS: Formalin-fixed and paraffin-embedded tissues from 184 cases of gastric carcinoma, its adjacent normal mucosa, IM and dysplasia were evaluated for the expression of PTEN by SABC immunohistochemistry. PTEN expression was assessed as to tumor stage, lymph node metastasis, Lauren's classification and WHO histological classification of gastric carcinoma. Expression of VEGF protein was also studied in 60 cases of gastric carcinoma, with its correlation with PTEN concerned. RESULTS: The positive rates of PTEN protein were 100% (102/102), 98.5% (65/66), 66.7% (4/6) and 47.8% (88/184) in normal mucosa, IM, dysplasia and carcinoma of stomach, respectively. The positive rates in the last two groups were lower than the first two (P < 0.01). PTEN was less expressed in advanced gastric carcinoma than in early ones (42.9% vs 67.6%, P < 0.01). The positive rate of PTEN protein was lower in gastric carcinoma with lymph node metastasis than without (40.3% vs 63.3%, P < 0.01). PTEN was less expressed in diffuse-type gastric carcinoma than in intestinal-type (41.5% vs 57.8%, P < 0.05). Signet ring cell carcinoma expressed PTEN stood the lowest (25.0%, 7/28), which was less than well and moderately differentiated ones (61.8%, 21/34) (P < 0.01). Expression of PTEN was inversely correlated with expression of VEGF though without any significance (P > 0.05). CONCLUSION: Loss or reduced expression of PTEN protein is common in carcinogenesis and progression of gastric cancer. Altered expression of PTEN may contribute to carcinogenesis and progression of gastric cancer by increasing angiogenesis, cellular adhesion and mobility and so on. PTEN may be an objective marker for pathologically biological behavior of gastric carcinoma.

Adult↗

Activation and overexpression of centrosome kinase BTAK/Aurora-A in human ovarian cancer.

Previous studies have demonstrated amplification of the centrosome serine/threonine kinase BTAK/Aurora-A in 10-25% of ovarian cancers. However, alterations of BTAK/Aurora-A at kinase and protein levels and its role in ovarian cancer progression have not been well documented. In this study, we examined the kinase activity and protein levels of BTAK/Aurora-A in 92 patients with primary ovarian tumors. In vitro kinase analyses revealed elevated BTAK/Aurora-A kinase activity in 44 cases (48%). Increased BTAK/Aurora-A protein levels were detected in 52 (57%) specimens. High protein levels of BTAK/Aurora-A correlated well with elevated kinase activity. Activation and overexpression of BTAK/Aurora-A were more frequently detected in early stage/low-grade ovarian tumors, although there was no statistic significance at the kinase level between early stage/low-grade and late stage/high-grade tumors. Moreover, BTAK/Aurora-A was preferentially expressed in noninvasive tumors, as revealed by immunohistochemical staining, suggesting that alterations of BTAK/Aurora-A could be an early event in human ovarian oncogenesis. To our knowledge, this is the first demonstration of recurrent activation and overexpression of BTAK/Aurora-A in human ovarian cancer, which may play a critical role in development of this malignancy.

Aurora Kinase A↗

[Identification of the two subtypes of latent autoimmune diabetes in adults by glutamic acid decarboxylase 65 antibody titers].

OBJECTIVE: To compare the clinical characteristics between type 2 diabetes and latent autoimmune diabetes in adults (LADA) and to define the two distinct types of LADA with different glutamic acid decarboxylase antibody (GADA) titers. METHODS: Sera of 750 patients with an initial diagnosis of type 2 diabetes mellitus (T2DM) were screened for GADA with radioimmunoprecipitation assay. The distribution and frequency of different GADA indices were described. Two hundred and ninety five patients were further studied and divided into four groups (T2DM; GADA index < 0.05; index > or = 0.5 and index > or = 0.05 but < 0.5) to compare the age of onset, body mass index, level of major component of adult hemoglobin (HbA1c) and C peptide as well as the rates of hypertension, hyperlipidemia and chronic complications. RESULTS: A total of 64 antibody-positive patients were identified. Compared with T2DM, these patients had younger age of onset, lower C peptide level (fasting C peptide 500 pmol/L vs 414 pmol/L, P < 0.01), lower body mass index (23.2 kg/m(2) vs 21.2 kg/m(2), P < 0.01) and also lower rates of hypertension (48.7% vs 31.7%, P < 0.05) and hyperlipidemia (60.2% vs 38.5%, P < 0.01). However, only the patients with high GADA titer had reduced beta cell function as compared with T2DM and low titer patients. Their diabetic complications were less than those of T2DM. Low GADA titer (index 0.05 - < 0.5) patients were similar to T2DM patients, except that they were prone to ketoacidemia. CONCLUSION: Two clinically distinct types of LADA can be identified by GADA titers. High titer GADA (GADA > or = 0.5) patients have more resemblance to insulin dependent diabetes and can be regarded as LADA-type 1 diabetes, while low titer GADA patients (0.05 - < 0.5) have clinical and metabolic phenotype of type 2 diabetes and can be regarded as LADA-type 2 diabetes.

Adult↗

[Long-term results of multimodality therapy of testicular germ cell tumor].

OBJECTIVE: To study the clinical characteristics, outcome, prognostic factors and survival of patients with testicular germ cell tumors (TGCTs). METHODS: 107 TGCT patients received chemotherapy after orchiectomy. The median age of the patients was 32 years. 30.8% (33/107) patients had seminomas with 14 (42.4%) stage I lesions. Seventy-four patients had non-seminomatous germ cell tumors (NSGCTT) with 21 (28.4%) stage I lesions. The response rate was analyzed with chi(2) test. The survival rate was calculated with Kaplan-Meier method and log-rank test. Therapy including chemotherapy, radiation and necessary salvage operation were performed after orchiectomy. RESULTS: Clinical stage and pathological type were the main prognostic factors. The 3-, 5- and 10-year survival rates were 75.8%, 73.5%, 73.5% for all patients, 100%, 96.8%, 96.8% for seminoma and 63.5%, 61.7%, 61.7% for NSGCTTs, respectively. Sixty-four patients were evaluable for response. Seventeen (26.6%) patients achieved CR by chemotherapy alone and an additional 8 patients (12.5%) achieved CR by chemotherapy plus salvage operation or radiation. The 5-year survival rates were 91.7% and 26.2% for patients who achieved CR or not. CONCLUSION: The long-term outcome for stage I germ cell tumors is excellent. The treatment outcome and survival in patients with metastatic TGCTs can be greatly improved by adopting multi-modality therapy with combined chemotherapy as the chief means.

Adolescent↗

[The effect of crystallization of calcium carbonate on the secondary structure of pepsin].

The effect of crystallization of calcium carbonate on the secondary structure of pepsin was studied by Fourier transform infrared spectroscopy, derivative, deconvolution and curve-fitting techniques in this paper. The result shows that the pure protein is composed of 24.38% alpha-helices, 29.91% beta-sheets, 39.22% beta-turns and 6.49% random structures, and the pepsin in the CaCO3/pepsin solution is composed of 2.09% alpha-helices, 93.304% beta-sheets, 4.60% beta-turns and 0.006% random structures. From these data we can see that the alpha-helices decrease and the beta-turns increase with the formation of the crystal of calcium carbonate. The essence of these changes is discussed in the paper.

Calcium Carbonate↗