Biomedical subjects

Bo Zhao

Publications and source records attributed to Bo Zhao.

At least 19 recordsLinked to original sources

PubMed2026

PASTA: versatile tyramide-oligonucleotide amplification for multimodal spatial biology.

Spatial proteomics is limited by detection sensitivity, multiplexing and multimodal integration, leaving a gap between discovery and clinical assays. Here we present protein and nucleic acid serial tyramide amplification (PASTA), using horseradish peroxidase-mediated oligonucleotide deposition and cyclical imaging for high-plex, multimodal spatial profiling. Compatible with conjugated antibodies and in situ hybridization, PASTA enables simultaneous protein and RNA codetection from formalin-fixed, paraffin-embedded samples, providing a cost-effective bridge from discovery to clinical validation.

Tyramine↗

PubMed2026

Positive feedback loop between RAF12 and ABI5 reinforces ABA-mediated suppression of Arabidopsis seed germination.

ABA-INSENSITIVE 5 (ABI5) is a key transcriptional regulator mediating abscisic acid (ABA)-induced suppression of seed germination. However, the downstream regulatory network through which ABI5 exerts its function remains incompletely understood. Here, by integrating ChIP-seq and RNA-seq analyses, we identify RAF12, a member of the B2 Raf-like kinase subfamily, as a direct transcriptional target of ABI5. ABI5 binds to the RAF12 promoter and activates its expression. Loss-of-function raf12 mutants exhibit reduced sensitivity to ABA during seed germination, suggesting a negative regulatory role for RAF12 in this process. Conversely, RAF12 interacts with and phosphorylates ABI5, thereby enhancing its transcriptional activity. Further analysis showed that RAF12 regulates its own kinase activity through autophosphorylation. Mutations at its phosphorylation sites significantly weaken its ability to enhance ABI5's transcriptional activity. Together, these findings uncover a positive feedback loop wherein ABI5 transcriptionally activates RAF12, which in turn reinforces ABI5 activity through phosphorylation. This module may function in parallel with the canonical SnRK2s-ABI5-mediated ABA signaling cascade, offering new mechanistic insights into the fine-tuning of ABA responses during seed germination.

Arabidopsis↗

PubMed2025

Exploring the Relationship Between Serological Metabolites and Oral Cancer: A Mendelian Randomization Study.

BACKGROUND: Oral cancer is a prevalent malignant tumor, comprising ∼5% to 6% of all tumors. The 5-year survival rate for this condition is ∼50%. However, the early symptoms of oral cancer are often inconspicuous and easily overlooked, leading to frequent misdiagnosis or missed diagnosis. Although some previous studies have investigated the correlation between oral cancer and serum metabolites, the exact relationship remains unclear. Consequently, it is of utmost importance to develop effective early diagnosis methods and explore the pathogenesis of oral cancer to enhance patients' survival rates and quality of life. METHODS: This Mendelian randomization (MR) study utilized the Genome-Wide Association Study (GWAS) catalog to obtain instrumental variables (IVs) that link 486 serum metabolites with oral cancer. The study then conducted a causal analysis, using serological metabolites as exposure factors and oral cancer as the outcome. The samples used in the study were exclusively from the European population. The main method used for the univariate MR analysis was the inverse variance weighting method. After excluding confounding factors, MR analysis was performed again. Sensitivity analyses were subsequently conducted to enhance the robustness of the MR results. Furthermore, metabolic pathway analysis was carried out on serum metabolites associated with oral cancer, aiming to identify and explore potential metabolic pathways. RESULTS: After MR analysis, 8 serum metabolites were screened out that are highly correlated with the causal relationship with oral cancer, including androsterone sulfate (OR=2.11, 95% CI: 1.37-3.27, P =0.0007), X-12100--hydroxytryptophan (OR=0.12, 95% CI: 0.02-0.73, P =0.022), gamma-glutamylphenylalanine (OR=7.57, 95% CI: 1.17-48.85, P =0.033), 7-methylxanthine (OR=0.22, 95% CI: 0.05-0.90, P =0.035), urate (OR=12.03, 95% CI: 1.16-124.32, P =0.037), palmate (16:0) (OR=11.01, 95% CI: 1.11-109.13, P =0.040), creatinine (OR=0.03, 95% CI: 0.00-0.90, P =0.047), guanosine (OR=2.66, 95% CI: 1.00-7.04, P =0.049), and the absence of heterogeneity and horizontal pleiotropy in this study indicates that the MR results obtained are quite reliable. CONCLUSION: Androsterone sulfate, gamma-glutamylphenylalanine, urate, palmitate (16:0), creatinine, and guanosine have been identified as risk factors for oral cancer. In contrast, X-12100--hydroxytryptophan and 7-methylxanthine may have a protective effect against oral cancer. The findings of this study have significant implications for early oral cancer diagnosis and offer valuable insights into the disease's pathogenesis.

Mendelian Randomization Analysis↗

PubMed2025

A six-repeat PPR protein WPR directly binds target RNAs and coordinates chloroplast RNA processing via dual recruitment of MORF1, MORF8b, and CAF2 proteins in rice.

Pentatricopeptide repeat (PPR) proteins are key regulators of organelle RNA metabolism in plants, yet their precise mechanisms in chloroplast RNA processing remain unclear. Here, we identify WPR, a unique P-type PPR protein in rice (Oryza sativa L.), as a critical factor in chloroplast RNA splicing and editing. A ~112-kb chromosomal inversion upstream of WPR causes an albino panicle rachis phenotype (wpr mutant), while complete loss of WPR function leads to seedling lethality. WPR deficiency disrupts the splicing of multiple group II introns (atpF, ndhA, ndhB, petB, rpl2, and rps12) and impairs RNA editing in transcripts such as ndhA, ndhB, ndhG, rps14, and ycf3. Electrophoretic mobility shift assay (EMSA) data confirm that WPR directly binds to precursor mRNAs of atpF, ndhA, petB, rpl2, and rps12. Strikingly, WPR interacts with both RNA editing factors (MORF1, MORF8b) and the splicing factor CAF2, but not with other PPR proteins targeting the same transcripts. Unlike most PPR proteins, WPR contains only six PPR repeats, which is the fewest among all functionally characterized rice PPR proteins. With few informative repeats, WPR likely possesses a broad, low-specificity RNA-binding activity. Moreover, WPR may act on chloroplast RNA maturation by recruiting MORFs and CAF2 rather than other PPR proteins, highlighting a novel regulatory mode in which P-type PPR protein may act as an RNA-binding scaffold to integrate diverse RNA-processing machineries. This study advances the understanding of PPR protein diversity and provides new insights into the molecular mechanisms of chloroplast RNA processing in rice.

Oryza↗

PubMed2006

Deterministic and storable single-photon source based on a quantum memory.

A single-photon source is realized with a cold atomic ensemble (87Rb atoms). A single excitation, written in an atomic quantum memory by Raman scattering of a laser pulse, is retrieved deterministically as a single photon at a predetermined time. It is shown that the production rate of single photons can be enhanced considerably by a feedback circuit while the single-photon quality is conserved. Such a single-photon source is well suited for future large-scale realization of quantum communication and linear optical quantum computation.

Journal Article↗

PubMed2006

Epstein-Barr virus EBNA-3C is targeted to and regulates expression from the bidirectional LMP-1/2B promoter.

Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA-3C) is essential for EBV-mediated immortalization of human B lymphocytes and regulates both the cell cycle and transcription. Transient reporter gene assays have implicated a pivotal role for EBNA-3C in the regulation of transcription of the majority of latency-associated genes expressed during the EBV growth program, including the viral oncoprotein LMP-1. To examine the regulation of latency gene expression by EBNA-3C, we generated an EBV-positive cell line that inducibly expresses EBNA-3C. This cell line allowed us to examine expression from the endogenous latency gene promoters in the context of an actual latent infection and the presence of other EBNA proteins, in particular EBNA-2, which is presumed to coregulate transcription with EBNA-3C. EBNA-3C induced the expression of both LMP-1 and LMP-2B mRNAs from the bidirectional LMP-1/LMP-2B promoter. In contrast, no effect was seen on expression from the common EBNA promoter Cp, which is responsive to EBNA-3C in reporter assays. Activation of LMP expression was not the consequence of increases in EBNA-2, PU.1 or Spi-B transcription factors, all of which are believed to be critical for activation of LMP-1. Chromatin immunoprecipitation assays furthermore indicated that EBNA-3C is present at the bidirectional LMP-1/LMP-2B promoter. These results indicate that EBNA-3C directly activates the expression of LMP-1 and LMP-2B but is unlikely to significantly regulate EBNA expression via Cp under normal growth conditions.

Antigens, Viral↗

PubMed2006

[Relationship between the adrenal function and the prognosis of acute respiratory distress syndrome].

OBJECTIVE: To explore the relationship between the adrenal function and the prognosis of acute respiratory distress syndrome (ARDS). METHODS: One hundred and fifty-eight patients with ARDS were enrolled in this study and were divided into two groups based on the prognosis: survival group and death group. Every patient was given one shot of corticotrophin 250 microg intravenously, plasma cortisol level was detected by radio-immunoassay before the shot (T0) and 30 minutes (T30) and 60 minutes (T60) after. And meanwhile the following parameters in the patients were recorded: age, APACH II, heart rate, mean arterial pressure, PaO(2)/FiO(2), arterial pH, hemoglobin, platelets and WBC, the number of failed organ and 28-day mortality. Relative adrenal insufficiency was defined as the difference between T0 and the highest value of T30 or T60 (DeltaTmax) <or= 248.4 nmol/L. RESULTS: The total 28-day mortality was 54.4% (86/158) and the total incidence of relative adrenal insufficiency was 42.7% (68/158). The incidence of relative adrenal insufficiency in death group was significantly higher than that in survival group (62.8% vs 19.4%, P < 0.01). The 28-day mortality in patients complicated with relative adrenal insufficiency was significantly higher than that in those did not (76.5% vs 36.8%, P < 0.001). The area under the ROC curve for DeltaTmax was 0.655. With the multivariate analysis, the number of failed organ and relative adrenal insufficiency were independent risk factors of the death in patients with ARDS. CONCLUSIONS: Adrenal function is valuable in predicting the prognosis of the ARDS.

Adolescent↗

PubMed2006

[The pathological characters and its clinical significance of internal hemorrhoids].

OBJECTIVE: To investigate the pathological characters and the corresponding clinical significance of internal hemorrhoids tissues. METHODS: Normal anal cushion and internal haemorrhoids tissue samples were obtained after stapled haemorrhoidectomy procedure from 24 grade III hemorrhoidal patients. The macroscopically normal cushions served as own controls and the normal cushions from a patient without a history of haemorrhoids as quality control. Routine Hematoxylin-Eosin and orcein were performed for elastic fibers. RESULTS: Compared with the corresponding normal anal cushions, the subepithelial vessels especially the cavernous vessels of the hemorrhoidal tissues showed obvious structural impair, retrograde changes, and the internal elastic lamina were ruptured and discontinuous. In addition, thrombosis and subsequent ischemic changes were observed. The Trietz's muscle and the fibro-elastic tissues showed hypertrophy, distortion, rupture and tortility. Obvious mucosal injury was observed in the mucous of hemorrhoidal tissues. Venous dilatation was infrequent in the hemorrhoidal tissues. CONCLUSIONS: The anal cushions of hemorrhoids disease patients show significant pathological changes. The pathological changes include structural impair, retrograde changes of the cavernous vessels and the hypertrophy, distortion, rupture and tortility of the Trietz's muscle and the fibroelastic tissues, and mucosal injury of the mucous membranes. These pathological changes are the basis of pathogenesis and development of hemorrhoids.

Adult↗

PubMed2006

RNAs induced by Epstein-Barr virus nuclear antigen 2 in lymphoblastoid cell lines.

Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA2) association with RBP-Jkappa is essential for regulation of virus and cell gene transcription and B lymphocyte transformation into infinitely proliferating lymphoblastoid cells (LCLs). To identify EBNA2-regulated cell genes in LCLs, an EBV recombinant that expresses EBNA2 with its C terminus fused in frame to a 4-hydroxytamoxifen (4HT)-dependent mutant estrogen receptor (E2HTF) was used to transform primary B lymphocytes to LCLs. In the presence of 4HT, E2HTF expression level and effects on the LMP1 promoter in transfected BJAB lymphoblasts were similar to EBNA2. In 4HT-supplemented medium, E2HTF EBV recombinant infected LCLs were also similar to EBNA2 LCLs in outgrowth but required higher serum and a restricted range of cell concentrations for consistent growth. In medium without 4HT, E2HTF localized to the cytoplasm, c-myc levels substantially decreased within 6 h, cells stopped growing, and levels of other EBNAs and LMP1 remained stable for 24 h. Over this 24-h period, 30 cell RNAs decreased 2-fold, and 51 other RNAs decreased 1.5-fold. These RNAs encode proteins important in cell adhesion or signaling, transcription, RNA processing, cell-cycle regulation, and survival. Real-time RT-PCR confirmed EBNA2-dependent expression of eight RNAs.

Cell Line↗

PubMed2006

Poleta, Polzeta and Rev1 together are required for G to T transversion mutations induced by the (+)- and (-)-trans-anti-BPDE-N2-dG DNA adducts in yeast cells.

Benzo[a]pyrene is an important environmental mutagen and carcinogen. Its metabolism in cells yields the mutagenic, key ultimate carcinogen 7R,8S,9S,10R-anti-benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide, (+)-anti-BPDE, which reacts via its 10-position with N2-dG in DNA to form the adduct (+)-trans-anti-BPDE-N2-dG. To gain molecular insights into BPDE-induced mutagenesis, we examined in vivo translesion synthesis and mutagenesis in yeast cells of a site-specific 10S (+)-trans-anti-BPDE-N(2)-dG adduct and the stereoisomeric 10R (-)-trans-anti-BPDE-N2-dG adduct. In wild-type cells, bypass products consisted of 76% C, 14% A and 7% G insertions opposite (+)-trans-anti-BPDE-N2-dG; and 89% C, 4% A and 4% G insertions opposite (-)-trans-anti-BPDE-N2-dG. Translesion synthesis was reduced by approximately 26-37% in rad30 mutant cells lacking Poleta, but more deficient in rev1 and almost totally deficient in rev3 (lacking Polzeta) mutants. C insertion opposite the lesion was reduced by approximately 24-33% in rad30 mutant cells, further reduced in rev1 mutant, and mostly disappeared in the rev3 mutant strain. The insertion of A was largely abolished in cells lacking either Poleta, Polzeta or Rev1. The insertion of G was not detected in either rev1 or rev3 mutant cells. The rad30 rev3 double mutant exhibited a similar phenotype as the single rev3 mutant with respect to translesion synthesis and mutagenesis. These results show that while the Polzeta pathway is generally required for translesion synthesis and mutagenesis of the (+)- and (-)-trans-anti-BPDE-N2-dG DNA adducts, Poleta, Polzeta and Rev1 together are required for G-->T transversion mutations, a major type of mutagenesis induced by these lesions. Based on biochemical and genetic results, we present mechanistic models of translesion synthesis of these two DNA adducts, involving both the one-polymerase one-step and two-polymerase two-step models.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

PubMed2006

Immunization of mice with a DNA vaccine based on severe acute respiratory syndrome coronavirus spike protein fragment 1.

According to data in GenBank, a gene encoding SARS spike protein fragment 1 (S1) was synthesized. After recombination with an immunostimulatory sequence (ISS), the gene was cloned into the plasmid pIRES to produce pIRES-ISS-S1. On confirmation of the expression of S1 protein by indirect immunofluorescence assay (IFA), after the transfection of pIRES-ISS-S1 into BHK-21 cells, the DNA vaccine was repeatedly administrated to BALB/c mice. CD4+ and CD8+ spleen T lymphocytes were analyzed by flow cytometry (FCM) to evaluate T cell-mediated immune responses, the antigen-specific responses of T cells were evaluated by cytotoxic T lymphocyte (CTL) assay, and the level of IgG in antisera from immunized mice was determined by enzyme-linked immunosorbent assay. Results showed that the counts of spleen CD4+ and CD8+ T lymphocytes were increased, that the T cell-mediated immune responses showed antigen specificity, and that IgG was significantly induced with DNA vaccines pIRES-ISS-S1 and pIRES-S1 at titers of 1:320 and 1:160, respectively. These results are promising for the protective immunization of humans.

Amino Acid Sequence↗

PubMed2006

EBNA-3B- and EBNA-3C-regulated cellular genes in Epstein-Barr virus-immortalized lymphoblastoid cell lines.

The cellular pathways that Epstein-Barr virus (EBV) manipulates in order to effect its lifelong persistence within hosts and facilitate its transmission between hosts are not well understood. The EBV nuclear antigen 3 (EBNA-3) family of latent infection proteins consists of transcriptional regulators that influence viral and cellular gene expression in EBV-infected cells. To identify EBNA-3B- and EBNA-3C-regulated cellular genes potentially important for virus infection in vivo, we studied a lymphoblastoid cell line (LCL) infected with an unusual EBV mutant, where a genetic manipulation to delete EBNA-3B also resulted in a significant decrease in EBNA-3C expression and slower than normal growth (3B(-)/3C(low)). Transcriptional profiling was performed on the 3B(-)/3C(low) LCLs, and comparison of mutant and wild-type LCL profiles resulted in a group of 21 probe sets representing 16 individual genes showing statistically significant differences in expression. Further quantitative reverse transcription-PCR analyses comparing 3B(-)/3C(low) LCLs to a previously described EBNA-3B mutant (3B(-)) where EBNA-3C expression was normal revealed three potential EBNA-3B-repressed genes, three potential EBNA-3C-repressed genes, and two potential EBNA-3C-activated genes. The most highly EBNA-3C-repressed gene was Jagged1, a cell surface ligand and inducer of the Notch receptor signaling pathway that is usurped by EBV genes essential for B-cell immortalization. 3B(-)/3C(low) LCLs expressed increased levels of Jagged1 protein and were able to more efficiently induce functional Notch signaling, and this signaling was dependent on Notch cleavage by gamma-secretase. However, inhibiting gamma-secretase-mediated Notch cleavage did not rescue 3B(-)/3C(low) LCL growth, suggesting that EBNA-3C-mediated repression of this signaling pathway did not contribute to LCL growth in tissue culture. Similarly, expression of the chemokine receptor CXCR4 was reproducibly upregulated in EBNA-3B-null LCLs. Since deletion of EBNA-3B has no significant impact on B-cell immortalization in tissue culture, this finding suggested that EBNA-3B-mediated regulation of CXCR4 may be an important viral strategy for alteration of B-cell homing in the infected host. These studies identify two cellular genes that do not contribute to EBV-induced B-cell growth but whose expression levels are strongly EBNA-3 regulated in EBV-infected primary B cells. These EBV-manipulated cellular pathways may be important for virus survival or transmission in humans, and their independence from EBV-induced B-cell growth makes them potential targets for testing in vivo with the rhesus lymphocryptovirus animal model for EBV infection.

Antigens, Viral↗

PubMed2006

Virus and cell RNAs expressed during Epstein-Barr virus replication.

Changes in Epstein-Barr virus (EBV) and cell RNA levels were assayed following immunoglobulin G (IgG) cross-linking-induced replication in latency 1-infected Akata Burkitt B lymphoblasts. EBV replication as assayed by membrane gp350 expression was approximately 5% before IgG cross-linking and increased to more than 50% 48 h after induction. Seventy-two hours after IgG cross-linking, gp350-positive cells excluded propidium iodide as well as gp350-negative cells. EBV RNA levels changed temporally in parallel with previously defined sensitivity to inhibitors of protein or viral DNA synthesis. BZLF1 immediate-early RNA levels doubled by 2 h and reached a peak at 4 h, whereas BMLF1 doubled by 4 h with a peak at 8 h, and BRLF1 doubled by 8 h with peak at 12 h. Early RNAs peaked at 8 to 12 h, and late RNAs peaked at 24 h. Hybridization to intergenic sequences resulted in evidence for new EBV RNAs. Surprisingly, latency III (LTIII) RNAs for LMP1, LMP2, EBNALP, EBNA2, EBNA3A, EBNA3C, and BARTs were detected at 8 to 12 h and reached maxima at 24 to 48 h. EBNA2 and LMP1 were at full LTIII levels by 48 h and localized to gp350-positive cells. Thus, LTIII expression is a characteristic of late EBV replication in both B lymphoblasts and epithelial cells in immune-comprised people (J. Webster-Cyriaque, J. Middeldorp, and N. Raab-Traub, J. Virol. 74:7610-7618, 2000). EBV replication significantly altered levels of 401 Akata cell RNAs, of which 122 RNAs changed twofold or more relative to uninfected Akata cells. Mitogen-activated protein kinase levels were significantly affected. Late expression of LTIII was associated with induction of NF-kappaB responsive genes including IkappaBalpha and A20. The exclusion of propidium, expression of EBV LTIII RNAs and proteins, and up-regulation of specific cell RNAs are indicative of vital cell function late in EBV replication.

Blotting, Western↗

PubMed2006

[An effect of the peripheral nerve allograft with subcutaneous preservation at different times on the nerve regeneration].

OBJECTIVE: To study an effect of the peripheral nerve allograft with subcutaneous preservation at different times on the sciatic nerve regeneration in rats. METHODS: Fifty-five Wistar rats were used in this experiment, which were randomly divided into the following 5 groups: the experimental groups (Groups A, B, C, 10 rats), the control group (Group D, 10 rats), and the donor group (Group E, 15 rats). In the experimental groups, a 15-mm segment of the sciatic nerve harvested from the donors was separately inserted into the subcutaneous compartment on the left thigh after the 1-week (Group A), 2-week (Group B), and 3-week (Group C) preservation; the segment of the sciatic nerve in the subcutaneous compartment was removed and transplanted into a 10-mm defect of the right sciatic nerve, which was made immediately. In Group D, a 10-mm sciatic nerve defect was made and immediately repaired in situ on the right thigh. The function of the sciatic nerve was evaluated by the sciatic functional index (SFI) at 2, 4, 6, 8, 10 and 12 weeks after operation. The histological and electrophysiological examinations were performed at 12 weeks after operation. RESULTS: After operation, SFI decreased gradually at 12 weeks after operation, SFI in Groups A and D was at the minimal level and had a significant difference compared with that in Groups B and C (P < 0.05). There was no significant difference between Group A and Group D. A large number of the myelinated nerve fibers and a small number of the unmyelinated nerve fibers were regenerated in Groups A and D. The number and the structure of the regenerated nerve were similar to the normal ones. The number and the size of the regenerated axon had a significant difference compared with those in Groups B and C (P < 0.05). There was no significant difference between Group A and Group D. The conduction velocity and the latent period of the motor nerve had significant differences between Groups A and D and Groups B and C (P < 0.05), and there was no significant difference between Group A and Group D. CONCLUSION: The nerve allograft with a 1-week subcutaneous preservation can promote nerve regeneration better.

Animals↗

PubMed2006

[Cardiac valve MCSF-1 and its receptor expression changes in Staphylococcus aureus induced infective endocarditis].

OBJECTIVE: To explore the cellular immunology mechanism of infective endocarditis (IE), we investigated the effects of Staphylococcus aureus (S. aureus) on MCSF-1 and its receptor (c-fms) gene expression in cardiac valves. METHODS: Thirty-two rabbits were divided into 4 groups: mitral or tricuspid valve artificial lesions with 5 x 10(4) CFU or 5 x 10(6) CFU S. aureus injection. Control rabbits (n = 7) received 5 x 10(6) CFU S. aureus injection. IE after operation were confirmed by naked eyes and electron microscope observations. MCSF-1, c-fms in mitral and tricuspid valves were detected by RT-PCR. RESULTS: Twenty-six rabbits survived the operation and 14 rabbits developed IE (2 with 5 x 10(4) CFU and 12 with 5 x 10(6) CFU S. aureus injection) one day post operation. S. aureus injection alone did not induce IE. Compared to control rabbits, MCSF-1 mRNA was significantly upregulated and c-fms mRNA significantly downregulated after 5 x 10(4) CFU S. aureus injection with heart valve artificial lesion in mitral valves or tricuspid valves. MCSF-1 expression in mitral valves was further increased while remained unchanged in tricuspid valve after 5 x 10(6) CFU S. aureus injection compared to that in 5 x 10(4) CFU S. aureus injection group. CONCLUSION: High dose bacterial invasion and heart valves lesion were the main factors for inducing infective endocarditis. Development of infective endocarditis was associated with valve MCSF-1/c-fms expression changes in this rabbit model.

Animals↗

PubMed2006

[Surgical treatment for tumors of trachea, carina and main bronchus].

OBJECTIVE: To review the experience in surgical treatment for tumors of trachea, carina and main bronchus. METHODS: From Jan. 1996 to Jun. 2004, 27 patients with tumor of trachea, carina or main bronchus underwent surgery including resection and reconstruction of trachea in 8, right/left pneumonectomy and carinal resection and reconstruction in 9 (6/3), right sleeve upper lobectomy and carnial resection with reconstruction of trachea and carina in 2, carina resection and reconstruction in 3, tumor removal through tracheal windows in 5. CPB (cardiopulmonary bypass) was used in 2 patients during surgery. RESULTS: There were 3 peri-operative deaths caused by acute respiratory failure in 2 and severe postoperative bleeding in 1 case. After follow-up of more than 6 months, no death or post-operative complication occurred. CONCLUSION: Resection and reconstruction for patients with tumor of trachea, main bronchus or carina can be performed with excellent results using effective surgical and anaesthetic methods with or without CPB assistance.

Adenocarcinoma↗

PubMed2005

Mediation of Epstein-Barr virus EBNA-LP transcriptional coactivation by Sp100.

The Epstein-Barr virus (EBV) EBNA-LP protein is important for EBV-mediated B-cell immortalization and is a potent gene-specific coactivator of the viral transcriptional activator, EBNA2. The mechanism(s) by which EBNA-LP functions as a coactivator remains an important question in the biology of EBV-induced B-cell immortalization. In this study, we found that EBNA-LP interacts with the promyelocytic leukemia nuclear body (PML NB)-associated protein Sp100 and displaces Sp100 and heterochromatin protein 1alpha (HP1alpha) from PML NBs. Interaction between EBNA-LP and Sp100 was mediated through conserved region 3 in EBNA-LP and the PML NB targeting domain in Sp100. Overexpression of Sp100 lacking the N-terminal PML NB targeting domain, but not a mutant form of Sp100 lacking the HP1alpha interaction domain, was sufficient to coactivate EBNA2 in a gene-specific manner independent of EBNA-LP. These findings suggest that Sp100 is a major mediator of EBNA-LP coactivation. These studies indicate that modulation of PML NB-associated proteins may be important for establishment of latent viral infections, and also identify a convenient model system to investigate the functions of Sp100.

Antigens, Nuclear↗

PubMed2005

Transcriptional regulation of alpha5beta1 integrin, fibronectin, VCAM-1, MCSF-1/c-fms, and MCP-1 in atrioventricular valves after valvular surgery and Staphylococcus aureus bacteremia.

OBJECTIVE: The primary event in the development of infective endocarditis (IE) is bacterial adherence to damaged heart valves. This includes capture, adhesion and internalization of bacteria into host cells. METHODS: We determined in an experimental rabbit model for IE whether a transient bacteremia caused by Staphylococcus aureus and/or endothelial heart valve lesions induce transcriptional regulation of alpha(5)beta(1) integrin, fibronectin, vascular cell adhesion molecule-1 (VCAM-1), macrophage colony-stimulating factor-1 (MCSF-1), c-fms proto-oncogene (MCSF-1 receptor), and macrophage chemoattractant protein-1 (MCP-1) in mitral and tricuspid valves. RESULTS: No significant upregulation was found after isolated bacteremia. Six hours after surgical manipulation valvular endothelial lesions led to a distinct modulation in the mRNA expression of proinflammatory cytokines (MCSF-1 and MCP-1), VCAM-1 and alpha(5)beta(1) integrin. The most evident differences between the mitral and tricuspid valves were seen in the significant upregulation of VCAM-1 mRNA on the tricuspid valve in the surgical groups, whereas there was no effect on the mitral valve. MCSF-1 and MCP-1 were dramatically upregulated in both valves after surgery. CONCLUSIONS: During the host defence mechanisms in the development of IE proinflammatory cytokines, cellular adhesion molecules, and molecules of the fibronectin/integrin axis are activated, showing distinct differences in right- and left-sided heart valves.

Animals↗