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Biomedical subjects

Zhiyuan Zhang

Publications and source records attributed to Zhiyuan Zhang.

At least 19 recordsLinked to original sources

The Spatiotemporal Genetic Architecture of Seed Vigor in Upland Cotton.

Seed vigor underpins uniform crop establishment, but its dynamic genetics are understudied. Combining high-resolution temporal phenotyping and genomics in upland cotton, we used the SeedRanger platform to record 17 image-based traits every 30 min over 120 h, revealing stage-specific heritability and identifying 541 seed-vigor loci. These loci show extensive pleiotropy and temporal coordination, forming a genetic network that preserves developmental continuity; 8.9% overlap regions under domestication selection, indicating concurrent optimization with fiber yield. Functional validation of FLA2, a candidate gene underlying a dynamic QTL, implicates auxin-mediated control of radicle elongation and cotyledon development. This temporal framework exposes dynamic genetic architecture and breeding targets for high-vigor crops.

Gossypium↗

Selective labeling of proteins by using protein farnesyltransferase.

The challenging task of identifying and studying protein function has been greatly aided by labeling proteins with reporter groups. Here, we present a strategy that utilizes an enzyme that labels a four-residue sequence appended onto the C terminus of a protein, with an alkyne-containing substrate. By using a bio-orthogonal cycloaddition reaction, a fluorophore that carried an azide moiety was then covalently coupled to the alkyne appended on the protein. FRET was used to calculate a Förster (R) distance of 40 A between the eGFP chromophore and the newly appended Texas Red fluorophore. This experimental value is in good agreement with the predicted R value determined by using molecular modeling. The small recognition tag, the high specificity of the enzyme, and the orthogonal nature of the derivatization reaction will make this approach highly useful in protein chemistry.

Alkyl and Aryl Transferases↗

Identification of genes associated with cisplatin resistance in human oral squamous cell carcinoma cell line.

BACKGROUND: Cisplatin is widely used for chemotherapy of head and neck squamous cell carcinoma. However, details of the molecular mechanism responsible for cisplatin resistance are still unclear. The aim of this study was to identify the expression of genes related to cisplatin resistance in oral squamous cell carcinoma cells. METHODS: A cisplatin-resistant cell line, Tca/cisplatin, was established from a cisplatin-sensitive cell line, Tca8113, which was derived from moderately-differentiated tongue squamous cell carcinoma. Global gene expression in this resistant cell line and its sensitive parent cell line was analyzed using Affymetrix HG-U95Av2 microarrays. Candidate genes involved in DNA repair, the MAP pathway and cell cycle regulation were chosen to validate the microarray analysis results. Cell cycle distribution and apoptosis following cisplatin exposure were also investigated. RESULTS: Cisplatin resistance in Tca/cisplatin cells was stable for two years in cisplatin-free culture medium. The IC50 for cisplatin in Tca/cisplatin was 6.5-fold higher than that in Tca8113. Microarray analysis identified 38 genes that were up-regulated and 25 that were down-regulated in this cell line. Some were novel candidates, while others are involved in well-characterized mechanisms that could be relevant to cisplatin resistance, such as RECQL for DNA repair and MAP2K6 in the MAP pathway; all the genes were further validated by Real-time PCR. The cell cycle-regulated genes CCND1 and CCND3 were involved in cisplatin resistance; 24-hour exposure to 10 microM cisplatin induced a marked S phase block in Tca/cisplatin cells but not in Tca8113 cells. CONCLUSION: The Tca8113 cell line and its stable drug-resistant variant Tca/cisplatin provided a useful model for identifying candidate genes responsible for the mechanism of cisplatin resistance in oral squamous cell carcinoma. Our data provide a useful basis for screening candidate targets for early diagnosis and further intervention in cisplatin resistance.

Carcinoma, Squamous Cell↗

FSH directly regulates bone mass.

Postmenopausal osteoporosis, a global public health problem, has for decades been attributed solely to declining estrogen levels. Although FSH levels rise sharply in parallel, a direct effect of FSH on the skeleton has never been explored. We show that FSH is required for hypogonadal bone loss. Neither FSHbeta nor FSH receptor (FSHR) null mice have bone loss despite severe hypogonadism. Bone mass is increased and osteoclastic resorption is decreased in haploinsufficient FSHbeta+/- mice with normal ovarian function, suggesting that the skeletal action of FSH is estrogen independent. Osteoclasts and their precursors possess G(i2alpha)-coupled FSHRs that activate MEK/Erk, NF-kappaB, and Akt to result in enhanced osteoclast formation and function. We suggest that high circulating FSH causes hypogonadal bone loss.

Animals↗

Osteoporosis with increased osteoclastogenesis in hematopoietic cell-specific STAT3-deficient mice.

Hematopoietic cell-specific disruption of the STAT3 gene induces hyperproliferation of cells of the myeloid lineage. Osteoclasts (OC), the bone-resorbing cells, are generated from the same precursors as monocyte/macrophages. STAT3 mutant mice exhibit decreased bone density, bone volume, and increased numbers of TRAP-positive OC. In vitro generation of OC showed significantly greater numbers of OC in mutant mice. The increased numbers of Mac1+ cells and c-kit+ cells were detected by FACS analysis, suggesting an increased number of OC precursors. Treatment of splenocytes with CSF-1 and RANKL significantly increased the Mac-1+RANK+ cells, with much higher levels observed in cells from mutant mice compared with littermate controls. Besides enhanced number of Mac1+ OC precursors, we also identified an OC-generating Mac1- c-kit+ population in mutant mice which was absent in littermate controls. The Mac1- c-kit- cells did not generate OC. Finally, we determined that protein expression and mRNA level of c-fos, a transcription factor which is essential for OC differentiation, were enhanced in OC precursors of mutant mice, which may contribute to the osteopenic phenotype.

Animals↗

Thickness measurement of nanoscale polymer layer on polymer substrates by attenuated total reflection infrared spectroscopy.

For the first time, attenuated total reflection (ATR)-Fourier transform infrared (FT-IR) spectroscopy was utilized to measure the thickness (d0) of a nanoscale polymer layer on polymer substrate with significant credibility. First, a mathematical formula, A/A0 = 1 - 2d0/ d(p), was derived based on a self-defining subsection function (where d(p) was defined as depth of penetration of ATR and A and A0 were defined as the absorption band area of the characteristic functional group only contained in bulk substrate with a thin polymer layer attachment and the same group in blank substrate, respectively). On the mathematical model, through changing incidence angles, a series of values of A (A0) and corresponding d(p) were obtained, and when plotting A/A0 versus 2/d(p), d0 was obtained as the slope. With polystyrene (coating)/olypropylene (substrate) as a model system, we obtained the relevant values (d0). Comparing the results with the values of practical coating thickness (calculation and TEM observation), we found that this method was able to characterize well the thickness of a thin polymer layer on a polymer substrate in the range from 10 to 110 nm. Errors in the measurement were given and analyzed. Furthermore, this method was well applied in the thickness measurement of a polyacrylamide graft layer on a polypropylene film surface. The effect of pressure in the ATR technique on the coating thickness measurement was also discussed. In comparison with other methods such as XPS, SEM, TEM, and AFM, this approach based on a universal ATR technique was very convenient and fast. This method is expected to widen the application of the ATR-FT-IR technique and stimulate the further development of many fields such as surface self-assembly and surface functionlization.

Journal Article↗

[Repair and reconstruction of oral and maxillofacial defect--clinical analysis of 1973 cases].

OBJECTIVE: To compare the reconstructive method of oral and maxillofacial defect with free tissue flaps. METHODS: The clinical materials were collected from 1 973 reconstructive cases between January 2000 and June 2004 and analyzed in terms of the distribution of age, gender, disease type, defect location, reconstructive method and the incidence of vascular crisis of free flaps as well as success rate of free flap respectively. SAS 6. 12 was adopted for statistical analysis. RESULTS: A total of 1973 reconstructive cases included 764 in middle age (>45 years to < or =60 years, 38.72%), 527 in old age (>60 years, 26.71%), 450 young adults (>28 years to < or =45 years, 22.81%), 187 in young age (>14 years to < or =28 years, 9.48%) and 45 children (< or =14 years, 2.28%). The ratio of male to female was 1.5 : 1. The ratio of benign to malignancy lesion was 1 : 1.94. The tongue defect accounted for 20.63%, followed by mandibular defect(17.38%), parotid defect(13.74%), buccal defect(12.72%), maxillary defect (8.16%), oral pharynx defect (7.60%), floor of mouth defect (5.68%) and others (14.09%). Vascular free flap transfers accounted for 45.82%(904), followed by axial flap(38.17%, 753), random flap (10.19%, 201), a vascularized bone graft (1.52%, 30) and others(4.30%, 85). The most frequently used flap was the forearm flap(594 cases), followed by the fibula free flap(143 cases) and the pedicled pectoralis major myocutaneous flap(369 cases); these three flaps accounted for 56.06% (1106/1973). In 47 free tissue flaps (5.20%) having vascular crisis, 30 were saved (63.83%). The success rate of total free tissue flaps was 98.19% (923/940). CONCLUSION: The majority of reconstructive cases of oral and maxillofacial defects is the middle aged and the old aged male patients with malignancy. The tongue defect accounts for about one fifth of all the cases. The vascularized free flap has a high success rate, so it is a main method for reconstruction of oral and maxillofacial defects. The forearm flap, the fibular free flap and the pedicled pectoralis major myocutaneous flap are the main management for repairing oral and maxillofacial defects.

Adolescent↗

[Combined vascularized iliac osteo-musculo-cutaneous flap with zygomatic implant anchorage in reconstructing 1 case of maxillary defect].

OBJECTIVE: To reconstruct the maxillary defect by using free vascularized iliac osteo-musculo-cutaneous flap combined with immediate zygomatic implantation for early rehabilitation of maxillary contour and masticatory function. METHODS: In August 2003, the patient presented with deformity of left middle face (Brown II type defect) after subtotal maxillectomy. After hospitalization, a set of preoperative preparations were made, including spiral CT scanning, manufacture of nature size anatomical model and implantation protocol design. The maxillary defect was reconstructed with free vascularized iliac osteo-musculo-cutaneous flap combined with simultaneous insertion of one Bränemark zygomatic implant and two general implants. Six months later the prosthesis were placed. RESULTS: The vascularized osteo-musculo-cutaneous flap survived, the osseointegration was observed between bone and implant 6 months later. The contour of face and palate was satisfactory, the normal occluding relation was gained. The average masticatory force of operative side was 76.3% of the normal side. No tumor recurrence was noticed during the follow-up of 14 months. CONCLUSION: It is a reliable method for functional reconstruction of maxillary defect via vascularized iliac osteo-musculo-cutaneous flap combined with immediate zygomatic implantation.

Adult↗

The application of magnetic resonance imaging-guided fine-needle aspiration cytology in the diagnosis of deep lesions in the head and neck.

PURPOSE: Image-guided fine-needle aspiration cytology (FNAC) may be useful as an alternative diagnostic approach to lesions in the head and neck. This study reports on the use of magnetic resonance imaging (MRI)-guided FNAC for diagnostic evaluation of deep lesions in this region. MATERIALS AND METHODS: This was a prospective study of 12 patients with deep lesions in the head and neck who underwent MRI-guided FNAC at the Shanghai 9th People's Hospital. A 0.2-T open magnet was used for MRI and localization of the 20-gauge MRI-compatible needle. All of the aspirated samples were stained with hematoxylin and eosin and examined by a cytopathologist. RESULTS: The needle in all 12 cases was displayed on MRI in the central portion of the lesion under the guidance of MRI; 12 of 12 patients (100%) had diagnostic aspirations and none needed open biopsy for more specific histologic interpretation. Six of these 12 patients with tumors (4 malignant, 2 benign) underwent operative treatment with positive postoperative pathologic results. One patient had a diagnosis of inflammation. The diagnostic accuracy was 91.67% (11 of 12), the sensitivity was 85.71% (6 of 7), and the specificity was 100% (5 of 5). There were no false-positive results and 1 false-negative result, for a false-negative rate of 14.29% (1 of 7). All aspiration procedures were well tolerated and without complications. CONCLUSIONS: MRI-guided FNAC is a cost-effective tool for establishing tissue diagnosis as a primary investigative modality. It is helpful and accurate in the diagnosis of deep lesions in the head and neck and in follow-up of patients, thereby avoiding further surgical intervention.

Adolescent↗

TCM treatment of infectious atypical pneumonia--a report of 16 cases.

OBJECTIVE: To probe into the mechanism on TCM treatment of infectious atypical pneumonia (severe acute respiratory syndrome, SARS) and evaluate its feasibility and effectiveness. METHOD: Twelve TCM prescriptions of herbal drugs (orally or i.v.) were used to treat 16 cases of SARS without using glucocorticoids, anti-viral agents, immune-regulators or antibiotics (in case there was no definite bacterial infections). The symptoms, signs, chest roentgenograms and lab examinations were carefully monitored and recorded for evaluation of the effectiveness. RESULTS: The average fever abatement time was 4.44 +/- 1.46 days and the mean absorption time of gross pulmonary infiltration was 10.87 +/- 2.92 days. No exacerbation occurred during the treatment. CONCLUSION: TCM intervention could effectively control and alleviate the symptoms and prevent the disease from exacerbation.

Adult↗

Different cDNA microarray patterns of gene expression reflecting changes during metastatic progression in adenoid cystic carcinoma.

BACKGROUND: The metastatic ability of tumor cells is determined by level of expression of specific genes that may be identified with the aid of cDNA microarray containing thousands of genes and can be used to establish the expression profile of disease related genes in complex biological system. MATERIALS AND METHODS: Salivary adenoid cystic carcinoma cell line and its high metastases adenoid cystic carcinoma clone were used as model systems to reveal the gene expression alteration related to metastasis mechanism by cDNA microarray analysis. The correlation of metastatic phenotypic changes and expression levels of 4 selected genes (encoding CD98, L6, RPL29, and TSH) were further validated by using RT-PCR analysis of human tumor specimens from primary adenoid cystic carcinoma and corresponding metastasis lymph nodes. RESULTS: Of the 7,675 clones of known genes and expressed sequence tags (ESTs) that were analyzed, 30 showed significantly different (minimum 3 fold) expression levels in two cell lines. Out of 30 genes found differentially expressed, 18 were up regulated (with ratio more than 3) and 12 down regulated (with ratio less than 1/3). CONCLUSION: Some of these genes are known to be involved in human tumor antigen, immune surveillance, adhesion, cell signaling pathway and growth control. It is suggested that the microarray in combination with a relevant analysis facilitates rapid and simultaneous identification of multiple genes of interests and in this study it provided a profound clue to screen candidate targets for early diagnosis and intervention.

Journal Article↗

Receptor activator of NF-kappa B ligand stimulates recruitment of SHP-1 to the complex containing TNFR-associated factor 6 that regulates osteoclastogenesis.

Receptor activator of NF-kappaB ligand (RANKL) is essential for differentiation and function of osteoclasts. The negative signaling pathways downstream of RANKL are not well characterized. By retroviral transduction of RAW264.7 cells with a dominant negative Src homology 2 domain-containing phosphatase-1 (SHP-1)(C453S), we studied the role of tyrosine phosphatase SHP-1 in RANKL-induced osteoclastogenesis. Over-expression of SHP-1(C453S) significantly enhanced the number of tartrate-resistant acid phosphatase-positive multinuclear osteoclast-like cells in response to RANKL in a dose-dependent manner. RANKL induced the recruitment of SHP-1 to a complex containing TNFR-associated factor (TRAF)6. GST pull down experiments indicated that the association of SHP-1 with TRAF6 is mediated by SHP-1 lacking the two Src homology 2 domains. RANKL-stimulated IkappaB-alpha phosphorylation, IkappaB-alpha degradation and DNA binding ability of NF-kappaB were increased after over-expression of SHP-1(C453S). However, RANKL-induced phosphorylation of mitogen-activated protein kinases, extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase, was unchanged. In addition, SHP-1 regulated RANKL-stimulated tyrosine phosphorylation of p85 subunit of phosphatidylinositol 3 kinase and the phosphorylation of Akt. Increased numbers of osteoclasts contribute to severe osteopenia in Me(v)/Me(v) mice due to mutation of SHP-1. Like RAW264.7 cells expressing SHP-1(C453S), the bone marrow macrophages of Me(v)/Me(v) mice generated much more osteoclast-like cells than that of littermate controls in response to RANKL. Furthermore compared with controls, RANKL induces enhanced association of TRAF6 and RANK in both RAW264.7 cells expressing SHP-1(C453S) and bone marrow macrophages from Me(v)/Me(v) mice. Therefore, SHP-1 plays a role in signals downstream of RANKL by recruitment to the complex containing TRAF6 and these observations may help to understand the mechanism of osteoporosis in Me(v)/Me(v) mice.

Animals↗

[Test of transient expression of green fluorescent protein gene transferred to bone marrow stromal cells].

OBJECTIVE: To determine the optimized condition under which BMP expression vector will be constructed to transfect bone marrow stromal cells (MSCs), plasmid vector coding enhanced green fluorescence protein (EGFP) gene pEGFP was transferred into MSCs. The transfer efficiency and transient expression were subsequently tested. METHODS: pEGFP plasmid was amplified and tested by an enzyme cutting technique in vitro. MSCs, which were initially obtained from the bone marrow of rabbits, were cultured in vitro and transferred with pEGFP by means of lipofectamine media methods. The ratio of plasmid and lipofectamine was varied according to the experiment design. Transfer efficiency and transient expression were evaluated by fluorescent microscopy. RESULTS: Transfer efficiency was correlated with the ratio of plasmid and lipofectamine. The expression of EGFP began in 24 hours after transferring, reached maximum in 48-72 hours and decreased in 1 week, however there remained a weak expression for more than 3 weeks. CONCLUSION: The efficiency of transferring pEGFP into MSCs could achieve to 30% with proper ratio of plasmid and lipofactamine. pEGFP was an ideal transient expression vector for MSCs gene transference.

Animals↗

STAT3 deletion during hematopoiesis causes Crohn's disease-like pathogenesis and lethality: a critical role of STAT3 in innate immunity.

Signal transducer and activator of transcription 3 (STAT3) is a key transcriptional mediator for many cytokines and is essential for normal embryonic development. We have generated a unique strain of mice with tissue-specific disruption of STAT3 in bone marrow cells during hematopoiesis. This specific STAT3 deletion causes death of these mice within 4-6 weeks after birth with Crohn's disease-like pathogenesis in both the small and large intestine, including segmental inflammatory cell infiltration, ulceration, bowel wall thickening, and granuloma formation. Deletion of STAT3 causes significantly increased cell autonomous proliferation of cells of the myeloid lineage, both in vivo and in vitro. Most importantly, Stat3 deletion during hematopoiesis causes overly pseudoactivated innate immune responses. Although inflammatory cytokines, including tumor necrosis factor alpha and IFN-gamma, are overly produced in these mice, the NAPDH oxidase activity, which is involved in antimicrobial and innate immune responses, is inhibited. The signaling responses to lipopolysaccharide are changed in the absence of STAT3, leading to enhanced NF-kappa B activation. Our results suggest a model in which STAT3 has critical roles in the development and regulation of innate immunity, and deletion of STAT3 during hematopoiesis results in abnormalities in myeloid cells and causes Crohn's disease-like pathogenesis.

Animals↗

Craniofacial resection of advanced oral and maxillofacial malignant tumors.

OBJECTIVE: To evaluate the clinical outcome of craniofacial resection for advanced malignant tumors in oral and maxillofacial regions. METHODS: Forty-six patients who underwent craniofacial resection for malignancies involving the anterior and middle cranial fossa over a 20-year period between June 1978 and December 1997 at our department were evaluated. Twenty patients received radiation therapy and an adjuvant therapy after the operation. Eleven patients received chemotherapy of various types as an adjuvant therapy. RESULTS: The 3- and 5-year survival rates were 48.8% (20/41) and 35.1% (13/37), respectively, while the 10-year survival rate was 20% (4/20). CONCLUSIONS: Our results revealed good prospects of using craniofacial resection on patients with advanced malignancies in the oral and maxillofacial regions.

Adolescent↗

Identification of genes with consistent expression alteration pattern in ACC-2 and ACC-M cells by cDNA array.

OBJECTIVE: To investigate the molecular events and metastasis-related genes in ACC-2 and ACC-M cells of adenoid cystic carcinoma. METHODS: Adenoid cystic carcinoma cell line ACC-2 and a sample of adenoic cystic carcinoma cell clones highly metastatic to the lung (ACC-M) were investigated. ACC-2 and ACC-M cells were cultured and collected. Total RNA was extracted using standard Trizol RNA isolation protocol. The poly A mRNA was purified and labeled in reverse transcription using M-MLV reverse transcriptase in the presence of Easytides deoxyadenosin 5' triphosphate [alpha-(33)p]. A cDNA array was assembled with 7675 EST clones which represented the same number of independent single genes. Prepared nylon membranes were hybridized with the [alpha (33)p]-dATP labeled mRNA from ACC-2 and ACC-M cells. Membranes were exposed to phosphor screen. RESULTS: The high-through put analysis of gene expression pattern was obtained from ACC-2 and ACC-M cells by the hybridization of the cDNA array. The difference of parallel gene expression was analyzed. Genes were clustered according to their expression level in the ACC-M compared with ACC-2 cells. According to each gene's ratio of expression level, there were 17 genes which were upregulated with ratios over 3.0, and there were 12 genes which were downregulated with ratios below 0.33 (1/3.0 = 0.33). CONCLUSIONS: Significantly different expression patterns between ACC-2 and ACC-M by cDNA array were observed. The differences lie in signal pathways, tumor antigens, immune molecular and some unknown genes.

Adult↗

Direct-puncture embolization of intraosseous arteriovenous malformation of jaws.

PURPOSE: Our goal was to report our experience with direct-puncture embolization of intraosseous arteriovenous malformations (AVMs). PATIENTS AND METHODS: Three cases of AVM in the mandible and 2 cases of AVM in the maxilla comprised this study group. The patients were embolized with fiber coils through direct puncture, and the coils were placed directly into the center of the intraosseous lesion, in some cases in conjunction with polyvinyl alcohol foam and N-butyl-2-cyanoacrylate through vascular access. RESULTS: The acute arterial bleeding was controllable in 3 patients. The other 2 patients had pericoronal oozing bleeding and a warm soft pulsative mass on the left face, respectively; their symptoms and signs improved greatly. The pericoronal oozing of blood in all patients disappeared during a 3- to 13-month follow-up, and new bone formation was found on the follow-up radiography. CONCLUSIONS: The embolization of the AVM of jaws by direct percutaneous puncture in conjunction with endovascular therapy is effective and safe, but longer follow-up is required to determine the true efficacy of this method of treatment.

Adolescent↗

Comparative study of clinical manifestation, plain-film radiography, and computed tomographic scan in arteriovenous malformations of the jaws.

OBJECTIVE: The purpose of this study was to summarize the clinical manifestation, plain-film radiography, and computed tomographic (CT) scan features of arteriovenous malformations (AVMs) of the jaws on the basis of a series of 12 patients. STUDY DESIGN: This study group comprised twelve patients with AVM of the jaws from February 1996 to February 2001. Seven cases were located in the mandible, and 5 in the maxilla. Both plain-film radiography and CT scan were available for all cases. For the patients with lesions in the mandible, panoramic, posterioanterior, and lateral mandibular views were applied. Waters' position view and panoramic radiography were indicated for AVMs of the maxilla. RESULTS: Each patient with AVM of the maxillary bone had involvement of adjacent soft tissues. Various radiographic signs were noted, including erosion, coarse trabeculae, and apparent lack of any radiographic change, and CT scans featured cystic expansion of alveolar process with broken cortex. The radiographic signs and CT scan features of AVMs in the mandible were related to involvement of surrounding soft tissues. If involvement of the adjacent soft tissues was found, "soap bubble" radiolucency was shown radiographically and osteolytic expansion with perforation of cortex was present on CT scan. In cases without surrounding soft tissue involvement, the various radiographic signs included multilocular or unilocular radiolucency or coarse trabeculae; osteolytic expansions with intact cortex were found on CT scan. CONCLUSION: AVMs of the jaws showed intraosseous osteolytic expansion on CT scan but had variable appearance on plain-film radiographs.

Adolescent↗