Porphyrazines as molecular scaffolds: periphery-core spin coupling between metal ions of a schiff base porphyrazine.
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Journal Article↗
Biomedical subjects
Min Zhao
Publications and source records attributed to Min Zhao.
Physiological electric fields control the G1/S phase cell cycle checkpoint to inhibit endothelial cell proliferation.
Vascular endothelial cell (VEC) proliferation is a key event in angiogenesis and is tightly regulated. Electric potential differences exist around the vascular endothelium and give rise to endogenous electric fields (EFs), whether these EFs influence VEC proliferation is unclear. We exposed cultured VECs to applied EFs of physiological strengths for up to 72 h. EF at 50 or 100 mV/mm did not influence cell proliferation, but at 200 mV/mm, cell density, cell growth rate, and mitosis index decreased significantly. EF-induced reduction in VEC proliferation was not due to increased apoptosis, because caspase apoptosis inhibitor Z-VAD-FMK (20 microM), had no effect on this response. Rather, EF responses were mediated via decreased entry of cells into S phase from G1 phase, as shown by flow cytometry. Western blot showed that EFs decreased G1-specific cyclin E expression and increased cyclin/cyclin-dependent kinase complex inhibitor p27kipl expression. Thus EFs controlled VEC proliferation through induction of cell cycle arrest at G1 by down-regulation of cyclin E expression and up-regulation of p27kipl expression, rather than by promoting apoptosis. If control of the cell cycle by endogenous EFs extends beyond VECs, this would be of widespread biological significance in vivo.
Animals↗
Bi-directional migration of lens epithelial cells in a physiological electrical field.
An endogenous electric field (EF) exists in the vertebrate lens, but the influences of this on the functions of lens epithelial cells (LECs) are unclear. Because LECs from different regions experience different patterns of endogenous EFs and show striking differences in morphology and function, bovine LECs from different regions were cultured in an applied EF to mimic that occurring naturally. The migration of LECs from central and peripheral regions was both stimulated and directed by an applied EF. Field-directed cell migration required serum, or growth factors. Cells cultured in serum free medium lost directed migration completely and this was restored partially by the addition of basic fibroblast growth factor. The direction of cell migration depended on both EF-strength and the origin of the LECs. Both central and peripheral LECs moved anodally at 150-250mVmm(-1). In a low EF (50mVmm(-1)), peripheral LECs migrated in the opposite direction, cathodally, but central LECs did not respond. Peripheral LECs alone therefore showed field strength dependent, bi-directional migration. A physiological EF enhanced activation of ERK1/2, a signaling molecule in the MAP kinase pathway, and this also required serum. Interestingly, expression of active ERK1/2 was enhanced in peripheral LECs at both 50 and 200mVmm(-1), which stimulated migration in different directions. In central LECs, which showed directed migration only at higher EFs, active ERK1/2 was increased only at 200mVmm(-1). The MAP kinase inhibitor U0126 prevented activation of ERK1/2 in LECs and inhibited EF-directed migration, implicating MAP kinase signaling in directing the migration of LECs in a physiological EF.
Animals↗
Pediatric cancer pain management practices and attitudes in China.
Children with cancer often receive less adequate pain management than adults. This survey was designed to examine current practices, knowledge, and attitudes pertaining to pediatric pain management in China. Based on the choice of opioid use and self-identification as having a conservative or liberal approach to pain management, we identified two clusters. Members of cluster 1 (60%) had more conservative attitudes and did not perceive that young children experienced pain. Members of cluster 2 (40%) had more liberal attitudes. Four factors predicted conservative membership: never having prescribed opioids for cancer pain (OR=2.67, CI=1.11-6.45), use of placebos for pain management (OR=2.32, CI=1.05-5.08), belief that the adequacy of pain management was fair or good (OR=2.10, CI=1.31-3.37), and belief that children are less sensitive to pain (OR=1.96, CI=1.02-3.76). The top barriers to optimal pediatric pain management were identified as fear of opioid addiction and inadequate knowledge of pain management.
Adult↗
An oxygen-rich fill-and-flow channel biosensor.
An oxygen-rich fill-and-flow channel biosensor has been developed for the measurement of glucose in wine. Glucose oxidase (GOD), immobilised in carbon paste (CP), was located in a well adjacent to a downstream detector electrode. When the analyte solution flows, hydrogen peroxide produced in the enzyme reaction is swept down to the detector electrode. Mineral oil and Kel-F oil (poly(chlorotrifluorethylene)) were used to prepare an enzyme layer of GOD within a CP. The hydrophobicity of the CP confined the reaction between the enzyme and its substrate to the surface of the enzyme layer. The oxidation current of hydrogen peroxide was sensitive to the enzyme loading but insensitive to mass transport variations such as flow rate. This response was, therefore, limited by the kinetics of the reaction between the enzyme and the substrate. For Kel-F oil, which can support a high concentration of dissolved oxygen, good reproducibility and greater dynamic range was obtained and the response did not decrease after degassing for 40 min with argon. Analysis of wine samples showed good agreement with the values obtained by spectrophotometric enzyme assay.
Biosensing Techniques↗
Direct visualization of a stratified epithelium reveals that wounds heal by unified sliding of cell sheets.
Observing cells in their original niche is a key link between the information gleaned from planar culture and in vivo physiology and pathology. A new approach combining the transparency of the cornea, Hoffman modulation optics, and digital imaging allowed movements of individual corneal cells to be viewed directly in situ. 3-Dimensional time-lapse movies imaging unstained cells within the stratified corneal epithelium during wound healing were made. Tracking cell movements dynamically provided a definitive answer to the long-standing question: does a stratified epithelium heal by "sliding" of cell sheets as a coherent unit or do individual cells "leap frog" each other at the wound margin? A wound in the corneal epithelium healed primarily by sliding of the whole epithelium, with approximately 95% of cells moving with similar speed and trajectories and with little change in their relative position. Only 5% of cells changed layers, with equal proportions moving up or down. Epithelial healing in situ occurred in three phases: a latency, migration, and reconstruction phase. This model provides a unique system to study the behaviors of individual cells in their original niche. It shows that cells slide into a wound as a unified unit to heal a stratified epithelium.
Animals↗
Rha1, an Arabidopsis Rab5 homolog, plays a critical role in the vacuolar trafficking of soluble cargo proteins.
Rab proteins are members of the Ras superfamily of small GTP binding proteins and play important roles in various intracellular trafficking steps. We investigated the role of Rha1, an Arabidopsis Rab5 homolog, in intracellular trafficking in Arabidopsis protoplasts. In the presence of a dominant-negative mutant of Rha1, soluble vacuolar cargo proteins such as sporamin:green fluorescent protein (Spo:GFP) and Arabidopsis aleurain like protein:GFP are not delivered to the central vacuole; instead, they accumulate as a diffuse or punctate staining pattern within the cell. Spo:GFP at the punctate stains observed in the presence of hemagglutinin:Rha1[S24N] is colocalized with endogenous vacuolar sorting receptor (VSR(At-1)), which is known to localize primarily to the prevacuolar compartment, whereas Spo:GFP in the diffuse pattern is associated with tonoplasts. Furthermore, expression of Rha1[S24N] causes the secretion of a portion of the vacuolar proteins into medium. However, the inhibitory effect of Rha1[S24N] on vacuolar trafficking is relieved partially by coexpressed wild-type Rha1. Based on these results, we propose that Rha1 plays a critical role in the trafficking of soluble cargoes from the prevacuolar compartment to the central vacuole.
Arabidopsis↗
Electric fields and MAP kinase signaling can regulate early wound healing in lens epithelium.
PURPOSE: To use lens epithelial cell monolayer wounds as a model system for the aberrant cell migration underlying posterior capsule opacification (PCO) and to investigate the effects of an applied physiological electric field (EF) on monolayer wound healing. METHODS: Scratch wounds were made in cultured bovine lens epithelial monolayers, and the wounds were exposed to an EF, with or without U0126 treatment (an inhibitor of active extracellular signal-regulated kinase [ERK 1/2]). Serial wound images were taken and wound areas were measured. Western blot analysis and immunocytochemical staining for ERK 1/2 in the wounded monolayers were performed. RESULTS: An applied EF of a given polarity influenced the healing of lens epithelial monolayer wounds. Wounds facing the anode healed at normal rates, those facing the cathode closed much more slowly. U0126, an inhibitor of mitogen-activated protein kinase (MAPK) signaling, inhibited wound healing, with or without exposure to an EF. Western blot analysis showed that both wounding and application of an EF enhanced the activation of ERK 1/2 independently and that U0126 completely inhibited these activations of ERK 1/2 in monolayers. Immunocytochemical staining showed an asymmetric activation of ERK 1/2 in EF-exposed wounds, with much weaker fluorescence in cathode-facing wounds, which could contribute to differentially directed wound-healing rates in an EF. CONCLUSIONS: Exposure to an EF inhibited the healing of lens epithelial monolayer wounds facing the cathode. ERK signaling pathways were involved in healing of lens epithelial monolayer wounds and in the EF-directed migration of the wound edge. It may be possible to use an applied EF to regulate the aberrant migration of lens epithelial cells that results in PCO after cataract surgery.
Animals↗
[Mutations of fragile histidine triad gene in Peutz-Jeghers syndrome and canceration].
BACKGROUND & OBJECTIVE: Peutz-Jeghers syndrome (PJS) is an autosomal dominantly inherited disease. Fragile histidine triad (FHIT) gene is an important tumor suppressor gene at the fragile sites region of 3p14. The authors' previous study suggested that PJS patients might have a susceptible gene at the region of 3p14.2. This study was designed to reveal the relationship between the variant of FHIT gene in PJS and its canceration. METHOD: Mutations of FHIT gene in 15 PJS patients and 20 unaffected members in 6 PJS families were determined using denaturing high-performance liquid chromatography (DHPLC), polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP) and DNA sequencing techniques. RESULTS: A non-sense mutation and a frame-shift mutation were identified at codon 54(GAA to TAA) (exon 6) which led to the change of the amino acid from glutamic acid (Glu) to stop codon, and a guanine insertion at codon 62 in exon 6 resulting in a premature stop codon TGA at codon 111 in one PJS patient. A homozygous deletion and a synonymous mutation were detected in exon 8. The homozygous deletion of exon 8 in FHIT gene was found in two polyps tissues and two cancerous tissues. And in 3 sporadic cases, the patients and their mothers have the same bands of SSCP and the same elution profiles of DHPLC when exon 8 was amplified. The DNA sequencing result showed that a synonymous mutation (polymorphism) occurred at codon 98 [CAT (H)-->CAC (H)], this mutation resulted in no change of amino acid. In addition, one base substitute from A to G mutation at 5'end, +42 nucleotide in intron 6 of FHIT gene was detected in seven patients and two unaffected members. CONCLUSION: PJS patients have low frequency point mutation of FHIT gene and their cancerous tissues had homozygous deletions in FHIT gene. This study indicated that the mutations and deletions of FHIT gene in PJS may play a role in the development of PJS and their cancerations.
Acid Anhydride Hydrolases↗
[Resection of malignant tumors of the anterior skull base and the fronto-orbito-ethmoidal region by overturn of frontonasal flap].
OBJECTIVE: To introduce a better surgical approach for the resection of malignant tumors in the anterior skull base and in the fronto-orbito-ethmoidal region. METHODS: A "U" form incision on the bilateral superciliary arch was made and connected with the unhealthy nasal side incision. Then the frontal musculocutaneous flap was over-turned upward. The nasal pyramid was over-turned to the healthy side. The malignant tumors in the anterior skull base and the fronto-orbito-ethmoidal region were fully exposed and resected. RESULTS: From december 1986 to december 1996, 50 patients received tumour resection through this approach. Postoperatively, the one-year survival rate was 86.0% (43/50), the three-year survival rate was 62.0% (31/50), and the five-year survival rate was 44.0% (22/50). CONCLUSION: The frontonasal flap overturn approach provided good exposure of surgical field, avoided the coronal incision, and the reaction of brain was mild. We believe this surgical approach is superior to traditional combined craniofacial approach.
Adult↗
[Analysis of severe acute respiratory syndrome in Beijing].
OBJECTIVE: To study the clinical, laboratory, and radiologic features of 34 cases of severe acute respiratory syndrome (SARS) in Beijing. METHODS: All patients were admitted to the isolation wards. Their demographic, clinical, laboratory, and radiologic characteristics were analyzed. Univariate and multivariate analyses were performed. RESULTS: Eight patients came from a family, and 15 patients were medical staff. The mean age of patients was (33.4 +/- 13.4) years. The latent period varied from 2 to 14 days (median 4 days). The most common symptoms were fever (100%), palpitation (91.7%), myalgia (79.2%), headache (70.8%), diarrhea (73.9%) and cough (58.3%). The mean leucocyte count was (4.6 +/- 1.4) x 10(9)/L, and the mean lymphocyte ratio was 0.27 +/- 0.11. 68.4% of the patients had lymphopenia (absolute lymphocyte count < 1.3 x 10(9)/L). Other common findings included elevated levels of serum alanine aminotransferase, lactate dehydrogenase and erythrocyte sedimentation (76.2%, 28.6% and 47.8%, respectively), and decreased levels of serum iron and albumin (63.2% and 47.8%, respectively). Thirty-two cases had abnormal chest radiographs. In 2 cases in whom typical lung opacities could not be found on the initial plain chest radiographs, thoracic CT proved to be useful. Postmortem examination of 1 patient revealed marked edema with foci of hemorrhage and hyaline membrane formation in the lungs, hemorrhage necrosis and a obvious decline of cells in lymph glands. In a multivariate analysis (Stata 7.0), the independent predictor of an adverse outcome was advanced age (odds ratio per decade of life, 1.6; 95% CI, 1.08 to 2.63; P = 0.007). CONCLUSIONS: Fever, lymphopenia, low serum iron and chest radiograph are helpful to diagnose SARS early; age is the independent predictor of an outcome.
Adult↗
[An investigation of current situation of corneal donors action in Chongqing].
OBJECTIVE: To evaluate the current situation of corneal donors and possible way to improve the corneal donation program in the city of Chongqing. METHODS: (1) The 1,400 residents of Chongqing were randomly surveyed to understand their ideas and attitudes towards corneal donation and to evaluate the correlation between their knowledge and their participation in the program in May - December, 2001. (2) The sociology data of 1,278 registered donors in the Chongqing Eye Bank were analyzed from March 1999 to December 2001.(3) The social-medical data of 37 eye donors were analyzed from March 1999 to December 2001. RESULTS: (1) Results of the random survey: the response rate was 79.14% (1,108/1,400), 1,072 (76.57%) questionnaire met the criteria for further analysis.47.20% of 1,072 persons would like to be eye donors, 62.69% supported eye donation, 32.55% would only donate their cornea, but 90.49% did not register to be a donor at present. Of those surveyed, about 2/3 were not familiar with the Chongqing Eye Bank, most did not know how to become an eye donor, and 75.28% supported local legislation to regulate donation. (2) Data of 1,278 registered eye donors: 550 were males and 728 were females, 61.89% were 30 years old or younger, most were students, teachers, medical staff or white-collared workers in general, and more than half had a university level education. (3) Data of 37 eye donors: 25 were males and 12 were females, age range was 20 - 88 years old, the main causes of death were malignant tumors and cardio-cerebral vessel disorders, 59% had nine or less years of education while only 11% had a university level education, and nine were also cadaver donors. The clinical utilization rate of eyes was 73%. CONCLUSIONS: (1) There are a significant number of people who are willing to be eye donors. Education level and age do not affect their decision to become donors. (2) Only a small percentage of the mass are registered eye donors. (3) Legislation regarding eye donation should be enacted as soon as possible. (4) Corneal donations could be higher than those at present.
Adult↗
[Changes of blood cells in patients with severe acute respiratory syndrome].
OBJECTIVE: To investigate the changes of blood corpuscles of patients with severe acute respiratory syndrome (SARS) in Beijing. METHODS: Totally 43 patients (21 male and 22 female, 19-74 years old age range) diagnosed as of probable SARS were included in this study. Their corpuscles in the peripheral blood were tested every two days, and the results were analyzed. RESULTS: Patients with SARS were more likely to develop leukocytopenia, lymphopenia and thrombocytopenia in the early period of disease than those in control group. The situation, especially lymphopenia and thrombocytopenia, could not be reversed in patients who died. Persistent low counts of lymphocytes and platelets at presentation might be associated with adverse outcomes. CONCLUSION: Low counts of leukocytes, lymphocytes and platelets were common among patients in the early stage of SARS. Persistent Lymphopenia and thrombocytopenia may be associated with the prognosis.
Adult↗
Electrical cues regulate the orientation and frequency of cell division and the rate of wound healing in vivo.
Controlling cell division is fundamental. One environmental cue that exerts profound control over both the orientation and frequency of cell division in vivo is a naturally occurring, wound-induced electric field (EF). Wounds in rat corneas generate endogenous EFs in the plane of the epithelial sheet because the transcorneal potential difference (TCPD; +40 mV internally positive) collapses at the wound edge, but is maintained at normal levels at 0.5 mm back from the wound. We manipulated the endogenous EF this creates by using drugs with differing actions. The wound-induced EF controlled the orientation of cell division; most epithelial cells divided with a cleavage plane parallel to the wound edge and perpendicular to the EF vector. Increasing or decreasing the EF pharmacologically, respectively increased or decreased the extent of oriented cell division. In addition, cells closest to the wound edge, where the EF was highest, were oriented most strongly by the EF. Remarkably, an endogenous EF also enhanced the frequency of cell division. This also was regulated by enhancing or suppressing the EF pharmacologically. Because the endogenous EF also regulated the wound healing rate, it may act as one control of the interplay between cell migration and cell division during healing.
Aminophylline↗
Genetic analysis of the role of G protein-coupled receptor signaling in electrotaxis.
Cells display chemotaxis and electrotaxis by migrating directionally in gradients of specific chemicals or electrical potential. Chemotaxis in Dictyostelium discoideum is mediated by G protein-coupled receptors. The unique Gbeta is essential for all chemotactic responses, although different chemoattractants use different receptors and Galpha subunits. Dictyostelium amoebae show striking electrotaxis in an applied direct current electric field. Perhaps electrotaxis and chemotaxis share similar signaling mechanisms? Null mutation of Gbeta and cAMP receptor 1 and Galpha2 did not abolish electrotaxis, although Gbeta-null mutations showed suppressed electrotaxis. By contrast, G protein signaling plays an essential role in chemotaxis. G protein-coupled receptor signaling was monitored with PHcrac-green fluorescent protein, which translocates to inositol phospholipids at the leading edge of cells during chemotaxis. There was no intracellular gradient of this protein during electrotaxis. However, F-actin was polymerized at the leading edge of cells during electrotaxis. We conclude that reception and transduction of the electrotaxis signal are largely independent of G protein-coupled receptor signaling and that the pathways driving chemotaxis and electrotaxis intersect downstream of heterotrimeric G proteins to invoke cytoskeletal elements.
Actins↗
Amelioration of streptozotocin-induced diabetes in mice using human islet cells derived from long-term culture in vitro.
BACKGROUND: Long-term maintenance of the phenotype of beta cells in vitro is difficult. The objective of this study was to examine an in vitro method for preserving the capacity of adult human beta cells to express insulin. We evaluated the use of long-term cultured islet cells for the treatment of diabetic SCID mice. METHODS: Human islets were isolated from cadaveric donors. The islets were cultured as monolayers and clusters in repeating cycles for 4 months. Thereafter, the cells were tested in vitro for their capacity to express insulin and to secrete insulin in response to glucose challenge. Finally, the cluster-cultured cells were transplanted under the kidney capsule and into the kidney tissue in streptozotocin (STZ)-induced diabetic SCID mice. RESULTS: Approximately 3.6% of cultured islet cells in cluster phase expressed insulin at 4 months and this was confirmed using immuno-gold-labeling electron microscopy. The cultured islet cells secreted insulin in response to glucose challenge in a dose-dependent manner. After transplantation, the islet cells redifferentiated and generated >20% insulin positive cells. The 4-month cultured cells rendered the blood glucose level near normal in mild diabetic mice (7.25 mM+/-1.595 vs. 15.225 mM+/-2.55, P<0.0025). CONCLUSION: It is possible to preserve the capacity of adult human islets to express insulin over a 4-month period in vitro, and this capacity was enhanced significantly by transplantation into SCID mice. The described system will be useful in studies of beta cell proliferation and differentiation.
Animals↗
Membrane lipids, EGF receptors, and intracellular signals colocalize and are polarized in epithelial cells moving directionally in a physiological electric field.
Directed cell migration is essential for tissue formation, inflammation, and wound healing. Chemotaxis plays a major role in these situations and is underpinned by asymmetric intracellular signaling. Endogenous electric fields (EFs) are common where cell movement occurs, such as in wound healing, and cells respond to electric field gradients by reorienting and migrating directionally (galvanotaxis/electrotaxis). We show that a physiological EF redistributed both EGF (epidermal growth factor) receptors and detergent-insoluble membrane lipids asymmetrically, leading to cathodal polarization and enhanced activation of the MAP kinase, ERK1/2. This induced leading-edge actin polymerization in directionally migrating mammalian epithelial cells. Inhibiting the EGF receptor-MAP kinase signaling pathway significantly decreased leading edge actin asymmetry and directional migration. We propose a model in which EF-polarized membrane lipid domains and EGF receptors cause asymmetric signaling through MAP kinase, which drives directional cell migration. A comparison is made with the mechanisms underpinning chemotaxis.
Animals↗
Has electrical growth cone guidance found its potential?
Many neurobiologists spurn the existence and use of direct-current (DC) electric fields (EFs) in nervous system development and regeneration. This is despite direct measurement of EFs in embryos and adults, and evidence that EFs are required for normal development, dramatically influence the rate and direction of nerve growth in vitro, and promote nerve regeneration in vivo. The notion that growth cones use EFs as guidance cues was dismissed partly because there was no convincing evidence that naturally occurring EFs influence nerve growth at the single-cell level in vivo. Recent work indicates that growth cones can be guided by EFs in vivo and, intriguingly, that in vitro guidance by chemotropic gradients and EFs might invoke similar mechanisms. Ongoing clinical trials to assess the effectiveness of DC EFs in promoting the regeneration of human spinal cord could allow EFs to achieve their potential.
Animals↗