Search PubMed⌕ Search

Biomedical subjects

Jun Sun

Publications and source records attributed to Jun Sun.

At least 19 recordsLinked to original sources

Non-destructive prediction of lead content in oilseed rape leaves by fluorescence hyperspectral technology based on neural network.

Based on fluorescence hyperspectral imaging (FHSI), this study targeted rapid, non-destructive quantification of lead (Pb) content in oilseed rape leaves treated with varying silicon (Si) concentrations, acquiring fluorescence spectra over the 484.43-1001.61 nm wavelength range. To optimize spectral data quality, preprocessing methods (Savitzky-Golay smoothing, first derivative, detrending) were comprehensively compared. Characteristic wavelengths were then selected via interval variable iterative shrinkage, which effectively compressed data dimensionality and reduced computational load. A hybrid SE-CL1DA model, fusing a 1D convolutional neural network, a long short-term memory network and SE attention mechanism was constructed, with Bayesian optimization tuning hyperparameters to boost stability. The BO-SE-CL1DA outperformed both traditional machine learning and insufficiently optimized deep learning model (Rp2=0.9609, RMSE = 0.0377 mg/kg, RPD = 5.1736), thus enabling accurate Pb estimation, supporting Si-regulated heavy metal stress management and facilitating agricultural contamination monitoring.

Plant Leaves↗

Flagellin-induced tolerance of the Toll-like receptor 5 signaling pathway in polarized intestinal epithelial cells.

Salmonella typhimurium is a gram-negative enteric pathogen that invades the mucosal epithelium and is associated with diarrheal illness in humans. Flagellin from S. typhimurium and other gram-negative bacteria has been shown to be the predominant proinflammatory mediator through activation of the basolateral Toll-like receptor 5 (TLR5). Recent evidence has shown that prior exposure can render immune cells tolerant to subsequent challenges by TLR ligands. Accordingly, we examined whether prior exposure to purified flagellin would render human intestinal epithelial cells insensitive to future contact. We found that flagellin-induced tolerance is common to polarized epithelial cells and prevents further activation of proinflammatory signaling cascades by both purified flagellin and Salmonella bacteria but does not affect TNF-alpha stimulation of the same pathways. Flagellin tolerance is a rapid process that does not require protein synthesis, and that occurs within 1 to 2 h of flagellin exposure. Prolonged flagellin exposure blocks activation of the NF-kappaB, MAPK, and phosphoinositol 3-kinase signaling pathways and results in the internalization of a fraction of the basolateral TLR5 without affecting the polarity or total expression of TLR5. After removal of flagellin, cells require more than 24 h to fully recover their ability to mount a normal proinflammatory response. We have found that activation of phosphoinositol 3-kinase and Akt by flagellin has a small damping effect in the early stages of flagellin signaling but is not responsible for tolerance. Our study indicates that inhibition of TLR5-associated IL-1 receptor-associated kinase-4 activity occurs during the development of flagellin tolerance and is likely to be the cause of tolerance.

Animals↗

Rational selection of small molecules that increase transcription through the GAA repeats found in Friedreich's ataxia.

Friedreich's ataxia (FRDA) is an autosomal recessive trinucleotide repeat disease with no effective therapy. Expanded GAA repeats in the first intron of the FRDA gene are thought to form unusual non-B DNA conformations that decrease transcription and subsequently reduce levels of the encoded protein, frataxin. Frataxin plays a crucial role in iron metabolism and detoxification. To discover small molecules that increase transcription through the GAA repeat region in FRDA, we have made stable cell lines containing a portion of expanded intron 1 fused to a GFP reporter. Small molecules identified using the competition dialysis method were found to increase FRDA-intron 1-reporter gene expression. One of these compounds, pentamidine, increases frataxin levels in patient cells. Thus our approach can be used to detect small molecules of potential therapeutic value in FRDA.

Antifungal Agents↗

WW domain binding protein-2, an E6-associated protein interacting protein, acts as a coactivator of estrogen and progesterone receptors.

WW domain binding protein-2 (WBP-2) was cloned as an E6-associated protein interacting protein, and its role in steroid hormone receptors functions was investigated. We show that WBP-2 specifically enhanced the transactivation functions of progesterone receptor (PR) and estrogen receptor (ER), whereas it did not have any significant effect on the androgen receptor, glucocorticoid receptor, or the activation functions of p53 and VP-16. Depletion of endogenous WBP-2 with small interfering RNAs indicated that WBP-2 was required for the proper functioning of PR and ER. We also demonstrated that WBP-2 contains an intrinsic activation domain. Moreover, chromatin immunoprecipitation assays demonstrate the hormone-dependent recruitment of WBP-2 onto an estrogen-responsive promoter. Mutational analysis suggests that one of three polyproline (PY) motifs of WBP-2 is essential for its coactivation and intrinsic activation functions. We show that WBP-2 and E6-associated protein each enhance PR function, and their effect on PR action are additive when coexpressed, suggesting a common signaling pathway. In this study, we also demonstrate that the WBP-2 binding protein, Yes kinase-associated protein (YAP) enhances PR transactivation, but YAP's coactivation function is absolutely dependent on WBP-2. Taken together, our data establish the role of WBP-2 and YAP as coactivators for ER and PR transactivation pathways.

Adaptor Proteins, Signal Transducing↗

Alterations in oxidative phosphorylation complex proteins in the hearts of transgenic mice that overexpress the p38 MAP kinase activator, MAP kinase kinase 6.

Ischemia-reperfusion (I/R) has critical consequences in the heart. Recent studies on the functions of I/R-activated kinases, such as p38 mitogen-activated protein kinase (MAPK), showed that I/R injury is reduced in the hearts of transgenic mice that overexpress the p38 MAPK activator MAPK kinase 6 (MKK6). This protection may be fostered by changes in the levels of many proteins not currently known to be regulated by p38. To examine this possibility, we employed the multidimensional protein identification technology MudPIT to characterize changes in levels of proteins in MKK6 transgenic mouse hearts, focusing on proteins in mitochondria, which play key roles in mediating I/R injury in the heart. Of the 386 mitochondrial proteins identified, the levels of 58 were decreased, while only 2 were increased in the MKK6 transgenic mouse hearts. Among those that were decreased were 21 mitochondrial oxidative phosphorylation complex proteins, which was unexpected because p38 is not known to mediate such decreases. Immunoblotting verified that proteins in each of the five oxidative phosphorylation complexes were reduced in MKK6 mouse hearts. On assessing functional consequences of these reductions, we found that MKK6 mouse heart mitochondria exhibited 50% lower oxidative respiration and I/R-mediated reactive oxygen species (ROS) generation, both of which are predicted consequences of decreased oxidative phosphorylation complex proteins. Thus the cardioprotection observed in MKK6 transgenic mouse hearts may be partly due to decreased electron transport, which is potentially beneficial, because damaging ROS are known to be generated by mitochondrial complexes I and III during reoxygenation.

Animals↗

Increased NF-kappaB activity in fibroblasts lacking the vitamin D receptor.

1,25-Dihydroxyvitamin D [1,25(OH)2D3] is known to have anti-inflammatory activity; however, the molecular mechanism remains poorly defined. Here we show that the nuclear vitamin D receptor (VDR) is directly involved in the regulation of NF-kappaB activation, a pathway essential for inflammatory response. In mouse embryonic fibroblasts (MEFs) derived from VDR-/- mice, the basal level of kappaB inhibitor (IkappaB) alpha protein was markedly decreased compared with VDR+/- MEFs; however, degradation of IkappaBalpha and its phosphorylation in response to TNF-alpha treatment or Salmonella infection were not altered in VDR-/- cells, neither were the levels of IkappaB kinase-alpha and IkappaB kinase-beta proteins. Consistent with IkappaBalpha reduction, p65 accumulation in the nucleus was markedly increased in unstimulated VDR-/- cells. In addition, the physical interaction between VDR and p65 was absent in VDR-/- MEFs, which may free p65 and increase its activity. Consequently, these alterations combined led to a marked increase in nuclear p65 DNA binding and NF-kappaB transcriptional activity; consistently, induction of IL-6 by TNF-alpha or IL-1beta was much more robust in VDR-/- than in VDR+/- cells, indicating that VDR-/- cells are more susceptible to inflammatory stimulation. Therefore, cells lacking VDR appear to be more proinflammatory due to the intrinsic high NF-kappaB activity. The reduction of IkappaBalpha in VDR-/- MEFs may be partially explained by the lack of VDR-mediated stabilization of IkappaBalpha by 1,25(OH)2D3. This is supported by the observation that IkappaBalpha degradation induced by TNF-alpha was inhibited by 1,25(OH)2D3 in VDR+/- cells, but not in VDR-/- cells. Taken together, these data suggest that VDR plays an inhibitory role in the regulation of NF-kappaB activation.

Animals↗

Salt stress in Desulfovibrio vulgaris Hildenborough: an integrated genomics approach.

The ability of Desulfovibrio vulgaris Hildenborough to reduce, and therefore contain, toxic and radioactive metal waste has made all factors that affect the physiology of this organism of great interest. Increased salinity is an important and frequent fluctuation faced by D. vulgaris in its natural habitat. In liquid culture, exposure to excess salt resulted in striking elongation of D. vulgaris cells. Using data from transcriptomics, proteomics, metabolite assays, phospholipid fatty acid profiling, and electron microscopy, we used a systems approach to explore the effects of excess NaCl on D. vulgaris. In this study we demonstrated that import of osmoprotectants, such as glycine betaine and ectoine, is the primary mechanism used by D. vulgaris to counter hyperionic stress. Several efflux systems were also highly up-regulated, as was the ATP synthesis pathway. Increases in the levels of both RNA and DNA helicases suggested that salt stress affected the stability of nucleic acid base pairing. An overall increase in the level of branched fatty acids indicated that there were changes in cell wall fluidity. The immediate response to salt stress included up-regulation of chemotaxis genes, although flagellar biosynthesis was down-regulated. Other down-regulated systems included lactate uptake permeases and ABC transport systems. The results of an extensive NaCl stress analysis were compared with microarray data from a KCl stress analysis, and unlike many other bacteria, D. vulgaris responded similarly to the two stresses. Integration of data from multiple methods allowed us to develop a conceptual model for the salt stress response in D. vulgaris that can be compared to those in other microorganisms.

Bacterial Proteins↗

[Relationship between trauma score and complications and interventions of traumatic patients in department of emergency medicine].

OBJECTIVE: To investigate the relationship between trauma score (TS) and complications and interventional strategies in trauma patients in the Emergency Department. METHODS: The injury severity was assessed with TS, and complications were recorded in 1 826 trauma patients in Emergency Department. The interventions, monitoring and imaging examinations were initiated promptly. RESULTS: The TS ranged from 1 to 16 points, and the lower the TS the poorer the patient's condition. The patients with score of 10 or above accounted for 73.06% of patients, those with score of 10 or below accounted for 26.94%. When they left Emergency Department in 91.84% of the patients TS was above 10, while 8.16% of them TS was 10 or below (both P<0.001). The patients with score of 10 or below had a higher rate of severe complications including hypotension, shock, abnormal respiration, and cardiac arrest. The lower the TS, the larger the amount of fluid resuscitation required. CONCLUSION: TS provides an objective value to indicate the seriousness of the patient's condition, and it is valuable to the attending to plan the strategies of intervention, monitoring and necessary instrumental examinations.

Adolescent↗

Burden of abnormal hematopoietic clone in patients with myelodysplastic syndromes.

OBJECTIVE: To investigate the role of the burden of abnormal hematopoietic clone in the development of myelodysplastic syndromes (MDS). METHODS: The ratio of the bone marrow cells with abnormal chromosomes to the total counted bone marrow cells was regarded as the index of MDS clone burden. The disease severity related parameters including white blood cell count, hemoglobin, platelet count, lactate dehydrogenase level, bone marrow blast, myeloid differentiation index, micromegakaryocyte, transfusion, interleukin-2, tumor necrosis factor (TNF), CD4+ and CD8+ T cells of MDS patients were assayed, and the correlations between those parameters and MDS clone burden were also analyzed. RESULTS: The clone burden of MDS patients was 67.4% +/- 36.2%. MDS clone burden positively correlated with bone marrow blasts (r = 0.483, P < 0.05), negatively with hemoglobin level (r = -0.445, P < 0.05). The number of blasts, hemoglobin, and erythrocytes in high clone burden (> 50%) and low clone burden ( < or = 50%) groups were 7.78% +/- 5.51% and 3.45% +/- 3.34%, 56.06 +/- 14.28 g/L and 76.40 +/- 24.44 g/L, (1.82 +/- 0.48) x 10(12)/L and (2.32 +/- 0.66) x 10(12)/L, respectively (all P < 0.05). CD4+ T lymphocytes of MDS patients and normal controls were (0.274 +/- 0.719) x 10(9)/L and (0.455 +/- 0.206) x 10(9)/L, respectively (P < 0.05). CD8+ T lymphocytes of MDS patients and normal controls were (0.240 +/- 0.150) x 10(9)/L and (0.305 +/- 0.145) x 10(9)/L, respectively. The serum level of interleukin-2 of MDS patients (6.29 +/- 3.58 ng/mL) was significantly higher than normal control (3.11 +/- 1.40 ng/mL, P < 0.05). The serum level of TNF of MDS patients and normal control group were 2.42 +/- 1.79 ng/mL and 1.68 +/- 0.69 ng/mL, respectively. The ratio of CD4 to CD8 was higher in high clone burden MDS patients (1.90 +/- 0.52) than that in low clone burden patients (0.97 +/- 0.44, P < 0.05). CONCLUSION: The quantitive clonal karyotype abnormalities and deficient T cell immunity are important parameters for evaluating MDS severity and predicting its progression.

Adolescent↗

Interactions between coilin and PIASy partially link Cajal bodies to PML bodies.

The eukaryotic nucleus contains a variety of dynamic structures, yet studies into the functional relationship of one type of subnuclear domain to another have been limited. For example, PML bodies and Cajal bodies associate, but the functional consequence of this association and the mediating factors are unknown. Here we report that an associated PML body/Cajal body can co-localize to an snRNA gene locus, with the Cajal body invariably situated between the PML body and the snRNA locus. Binding studies demonstrate that coilin (a Cajal body protein) directly interacts with PIASy (a PML body protein). Cell biological experiments using coilin and PIASy knockout cell lines demonstrate that interactions between coilin and PIASy account in part for the observed association of Cajal bodies with PML bodies. When the PIASy interaction region on coilin is deleted, the frequency of the association between Cajal bodies and PML bodies is reduced. These studies provide another example of coilin's role in the functional organization of the nucleus.

Chromosomal Proteins, Non-Histone↗

Glassy dynamics in the adaptive immune response prevents autoimmune disease.

The immune system normally protects the human host against death by infection. However, when an immune response is mistakenly directed at self-antigens, autoimmune disease can occur. We describe a model of protein evolution to simulate the dynamics of the adaptive immune response to antigens. Computer simulations of the dynamics of antibody evolution show that different evolutionary mechanisms, namely, gene segment swapping and point mutation, lead to different evolved antibody binding affinities. Although a combination of gene segment swapping and point mutation can yield a greater affinity to a specific antigen than point mutation alone, the antibodies so evolved are highly cross reactive and would cause autoimmune disease, and this is not the chosen dynamics of the immune system. We suggest that in the immune system's search for antibodies, a balance has evolved between binding affinity and specificity.

Animals↗

The hydroxyurea-induced small GTP-binding protein SAR modulates gamma-globin gene expression in human erythroid cells.

Hydroxyurea (HU), a drug effective in the treatment of sickle cell disease, is thought to indirectly promote fetal hemoglobin (Hb F) production by perturbing the maturation of erythroid precursors. The molecular mechanisms involved in HU-mediated regulation of gamma-globin expression are currently unclear. We identified an HU-induced small guanosine triphosphate (GTP)-binding protein, secretion-associated and RAS-related (SAR) protein, in adult erythroid cells using differential display. Stable SAR expression in K562 cells increased gamma-globin mRNA expression and resulted in macrocytosis. The cells appeared immature. SAR-mediated induction of gamma-globin also inhibited K562 cell growth by causing arrest in G1/S, apoptosis, and delay of maturation, cellular changes consistent with the previously known effects of HU on erythroid cells. SAR also enhanced both gamma- and beta-globin transcription in primary bone marrow CD34+ cells, with a greater effect on gamma-globin than on beta-globin. Although up-regulation of GATA-2 and p21 was observed both in SAR-expressing cells and HU-treated K562 cells, phosphatidylinositol 3 (PI3) kinase and phosphorylated ERK were inhibited specifically in SAR-expressing cells. These data reveal a novel role of SAR distinct from its previously known protein-trafficking function. We suggest that SAR may participate in both erythroid cell growth and gamma-globin production by regulating PI3 kinase/extracellular protein-related kinase (ERK) and GATA-2/p21-dependent signal transduction pathways.

Antigens, CD34↗

Crosstalk between NF-kappaB and beta-catenin pathways in bacterial-colonized intestinal epithelial cells.

Salmonella-epithelial cell interactions are known to activate the proinflammatory NF-kappaB signaling pathway and have recently been found to also influence the beta-catenin signaling pathway, an important regulator of epithelial cell proliferation and differentiation. Here, using polarized epithelial cell models, we demonstrate that these same bacteria-mediated effects also direct the molecular crosstalk between the NF-kappaB and beta-catenin signaling pathways. Convergence of these two pathways is a result of the direct interaction between the NF-kappaB p50 subunit and beta-catenin. We show that PhoP(c), the avirulent derivative of a wild-type Salmonella strain, attenuates NF-kappaB activity by stabilizing the association of beta-catenin with NF-kappaB. In cell lines expressing constitutively active beta-catenin, IkappaBalpha protein was indirectly stabilized and NF-kappaB activity was repressed after wild-type Salmonella colonization. Accordingly, constitutively active beta-catenin was found to inhibit the secretion of IL-8. Thus our findings strongly suggest that the crosstalk between the beta-catenin and NF-kappaB signaling pathways is an important regulator of intestinal inflammation.

Cytoskeletal Proteins↗

Chitosan-glycerol phosphate/blood implants improve hyaline cartilage repair in ovine microfracture defects.

BACKGROUND: Microfracture is a surgical procedure that is used to treat focal articular cartilage defects. Although joint function improves following microfracture, the procedure elicits incomplete repair. As blood clot formation in the microfracture defect is an essential initiating event in microfracture therapy, we hypothesized that the repair would be improved if the microfracture defect were filled with a blood clot that was stabilized by the incorporation of a thrombogenic and adhesive polymer, specifically, chitosan. The objectives of the present study were to evaluate (1) blood clot adhesion in fresh microfracture defects and (2) the quality of the repair, at six months postoperatively, of microfracture defects that had been treated with or without chitosan-glycerol phosphate/blood clot implants, using a sheep model. METHODS: In eighteen sheep, two 1-cm2 full-thickness chondral defects were created in the distal part of the femur and treated with microfracture; one defect was made in the medial femoral condyle, and the other defect was made in the trochlea. In four sheep, microfracture defects were created bilaterally; the microfracture defects in one knee received no further treatment, and the microfracture defects in the contralateral knee were filled with chitosan-glycerol phosphate/autologous whole blood and the implants were allowed to solidify. Fresh defects in these four sheep were collected at one hour postoperatively to compare the retention of the chitosan-glycerol phosphate/blood clot with that of the normal clot and to define the histologic characteristics of these fresh defects. In the other fourteen sheep, microfracture defects were made in only one knee and either were left untreated (control group; six sheep) or were treated with chitosan-glycerol phosphate/blood implant (treatment group; eight sheep), and the quality of repair was assessed histologically, histomorphometrically, and biochemically at six months postoperatively. RESULTS: In the defects that were examined one hour postoperatively, chitosan-glycerol phosphate/blood clots showed increased adhesion to the walls of the defects as compared with the blood clots in the untreated microfracture defects. After histological processing, all blood clots in the control microfracture defects had been lost, whereas chitosanglycerol phosphate/blood clot adhered to and was partly retained on the surfaces of the defect. At six months, defects that had been treated with chitosan-glycerol phosphate/blood were filled with significantly more hyaline repair tissue (p < 0.05) compared with control defects. Repair tissue from medial femoral condyle defects that had been treated with chitosan-glycerol phosphate/blood contained more cells and more collagen compared with control defects and showed complete restoration of glycosaminoglycan levels. CONCLUSIONS: Solidification of a chitosan-glycerol phosphate/blood implant in microfracture defects improved cartilage repair compared with microfracture alone by increasing the amount of tissue and improving its biochemical composition and cellular organization.

Animals↗

Experimental study and clinical observation of minimum-contact plate in long bone fracture.

OBJECTIVE: To study the mechanical properties and the clinical results of minimum-contact plate in the treatment of fractures. METHODS: Four-point bending and torsion tests were conducted to compare the new minimum contact plate (MCP) with dynamic compression plate (DCP) and limited contact dynamic compression plate (LC-DCP). The fracture healing time and growth of bony callus were observed in 29 cases of long bone fracture fixed with MCP to evaluate the advantages of this kind of plate. RESULTS: The 29 patients who underwent MCP were followed up from 6 to 14 months. The average healing time for femoral, tibial and humeral fractures was 12, 13 and 10 weeks, respectively. All fractures were healed. No displacement of fracture, screw pullout, deformation or break of the plate were found. CONCLUSIONS: The bending stiffness of MCP is significantly greater than that of DCP and LC-DCP (P<0.05). MCP can protect the periosteal blood supply against avascular osseous necrosis and accelerate bone healing. It is a kind of reliable and effective plate in treatment of fractures.

Adolescent↗

[Effect of thickness and shade of porcelain of ceramometal restorations on color of gingival porcelain].

OBJECTIVE: The purpose of this study was to evaluate the color changes of gingival porcelain through varying thickness and shade of porcelain of ceramometal restorations. METHODS: In this study a spectrophotometer (PR-650) was used for color analysis. The color changes of dentin porcelain and gingival porcelain with three varied thickness (0.3 mm, 0.6 mm and 0.9 mm) were investigated. In addition, the color variances of Shofu vintage porcelain shade A2, A3 and B2 were tested. RESULTS: The results showed that decreased L * value of ceramometal restorations and increased a * value were due to the increase of the gingival porcelain thickness, color measurements showed the same trend as the increased dentin porcelain thickness and the opaque and dentin porcelain with different color affected the appearance of gingival porcelain. CONCLUSION: The color of gingival porcelain would be changed with the differences of thickness and shade of porcelain of ceramometal restorations.

Color↗

[Analysis of chromatic value of gingival porcelain].

OBJECTIVE: To study the distribution of the chromatic value of gingival porcelains. METHODS: The color change of Shofu VINTAGE and Vita VMK95 gingival porcelains on the black and white backings was determined with a spectrophotometer (PR-650). RESULTS: The results showed that the chromatic value of gingival porcelains was different on varying backings. The color space of gingival porcelain was L*: 41.85 - 50.64, a*: 12.46 - 19.46, b*: 1.33 - 4.62. CONCLUSION: The chromatic value distribution cannot cover the color region of natural gingiva.

Color↗