Hypoxia is a general characteristic of most solid malignancies and intimately related to cancer progression. Homeostatic response to hypoxia is primarily mediated by hypoxia inducible factor-1alpha (HIF-1alpha) that elicits transcriptional activity through recruitment P300 coactivator. Targeting the interaction of HIF- alpha and P300 would thus constitute a novel approach for cancer treatment by suppressing tumor angiogenesis and metastasis. Here, a screening assay was developed for inhibitors targeting the interaction between HIF-1alpha and P300. The nucleotide sequence of human HIF-1alpha and P300 were cloned into pBIND and pACT vectors, named pBIND-HIF1alpha and pACT-P300. The interaction of HIF-1alpha and P300 was identified in HEK293 cell using mammalian two-hybrid system. And compound chetomin decreased their interaction in this mammalian two-hybrid system. We further verified HIF-1 inhibition effect of chetomin in U251-HRE cells. Therefore, we established a screening assay combined HIF-1alpha and P300 mammalian two-hybrid system and U251-HRE reporter assay for HIF-1 selective inhibitors.
Cell Hypoxia ; Disulfides ; pharmacology ; Drug Screening Assays, Antitumor ; E1A-Associated p300 Protein ; antagonists & inhibitors ; HEK293 Cells ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; antagonists & inhibitors ; Indole Alkaloids ; pharmacology ; Two-Hybrid System Techniques

Spectral karyotyping (SKY) is a novel cytogenetic technique, has been developed to unambiguously display and identify all 24 human chromosomes at one time without a priori knowledge of any abnormalities involved. SKY discerns the aberrations that can not be detected very well by conventional banding technique and fluorescent in situ hybridization (FISH). So SKY is hyper-accurate, hypersensitive, and hyper-intuitional. In this paper the basic principle of SKY technique and its application in leukemia cytogenetics were reviewed.
Humans ; Karyotyping ; Leukemia ; genetics ; pathology ; Spectral Karyotyping

Background There are a lot of studies about the carrier of corneal endothelial transplantation,but the best carrier has not been defined.Objective This study was to investigate the biocompatibility of chitosan carrier with rabbit corneal endothelium in vivo.Methods Fresh eye-balls were obtained from 10 New Zealand white rabbits.Rabbit corneal endothelial cells (CECs) were isolated and cultured on chitosan carrier in vitro.The morphology and density of rabbits CECs were observed every day,and the expressions of fibronectin (FN),collagen-1 (Coil-I) and Zonula occludens 1 (ZO-1) were detected by immunoinfluorescence.The morphology and ultrastructure of CECs were observed under the scanning and transmission electron microscope.Chitosan carrier with CECs was implanted into the anterior chamber of the left eyes in ten healthy New Zealand white rabbits,and only paracentesis of anterior chamber was performed in the right eyes as controls.The inflammation of ocular anterior segment was examined under the slit lamp microscope,and corneal thickness was measured 1 week,4 and 8 weeks after operation.Corneal endothelium cell density and morphology were examined under the corneal endothelial microscope at postoperative 2 weeks.Corneal samples were collected for the regular histopathological examination to observe the inflammatory reaction at postoperative 1 month and 3 months.Paired t test was used for statistical analyses between the control group (left eyes) and the experimental group (right eyes).The use and care of the animals followed the Statement of ARVO.Results CECs formed an intact monolayer of cells with the uniform shape and size on the chitosan membrane after incubated for 5 days.The cells reached confluence of 90％ 7 days after cultured with the 40％ hexagon cells.Under the scanning electron nicroscope,rabbit CECs showed the round or polygon in the shape with the microvillus on the cell surface.The cells connected closely by desmosome.The processes,pseudopodiums and microvillus on the cellular surface,vacuole in the cytoplasm,expanded endoplasmic reticulum with ribosome and abundant chromatin were exhibited under the transmission electron microscope.The immunofluorescence examination revealed the positive expressions of FN,Coll-Ⅰ and ZO-1 in the CECs on the chitosan carrier.In the in vivo experiment,the exudation in the anterior chamber and corneal edema were seen under the slit lamp microscope 3 days after implantation of chitosan carrier with CECs.However,the inflammation was gone 14 days after operation.The differences of the corneal thickness were no significant between the experimental group and the control group 1 week and 4,8 weeks after operation (t =1.377,P=0.265;t =1.795,P=0.165 ; t =0.390,P =0.760).In addition,no significant differences were found in the CECs density and the hexagon cells rate between the two groups(P =0.365,0.062).The histopathological examination showed that the inflammatory cells around the chitosan membrane were disappeared 3 months after operation and showed a good corneal structure.Conclusions Chitosan carrier has a good biocompatibility with rabbit CECs and anterior chamber,and it may be a potentially good carrier for CECs transplantation.

OBJECTIVETo evaluate the therapeutic effect of Liujunzi decoction combined with Zuojin pills in treating the radioactive duodenitis and their mechanism, and compare with clinical routine acid suppressants combined with mucous membrane protective preparations to study the mechanism of their efficacy.

METHODAccording to the study of Williams J P and characteristics of duodenitis, and by reference to the radiation enteritis modeling standard, we took the lead in establishing the mouse radioactive duodenal injury model. The model mice were randomly divided into the control group (n = 26), traditional Chinese medicine (TCM) group (n = 16) and the western medicine (oral administration with famotidine 0.5 mL + almagate suspension 0.3 mL per mouse, once a day) group (n = 16). After the standard administrating, such objective indexes as general condition, weight, changes in health score, pathology and expression of inflammatory factors were observed to evaluate the efficacy.

RESULTThe radioactive duodenitis model of mice was successfully established with 12 Gy. Mice in the control group suffered from weight loss, anorexia, low fluid intake, loose stools, and occasionally mucous bloody stool, poor spirit, dim fur, lack of exercise and arch back. Mice in drug intervention groups were generally better than those in the pure irradiation group. The IL-6, IL-1beta, TNF-alpha mRNA expressions in spleen and mesenteric lymph node tissues in TCM and western medicine groups showed a declining trend compared with the control group. Their concentrations in peripheral blood serum also slightly changed. The TCM group revealed notable advantage in reducing inflammatory factors. The microscopic observation showed that a better mucosa repair in intervention groups than the pure irradiation group. The improved Chiu's scoring method showed a statistical significance in the difference between TCM and western medicine groups (P < 0.05).

CONCLUSIONLiujunzi decoction combined with Zuojin pills could treat acute radiation enteritis, regulate organic immunity, and inhibit acute injury, promote local tissue repair, with the potential to resist such adverse effects as radiation intestinal fibrosis. The regulation of inflammatory factor release is one of efficacy generation mechanisms.

Animals ; Cobalt Radioisotopes ; adverse effects ; Drug Interactions ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Duodenitis ; blood ; drug therapy ; Interleukin-1beta ; blood ; Interleukin-6 ; blood ; Mice ; Mice, Inbred BALB C ; Mucous Membrane ; drug effects ; radiation effects ; Radiation Injuries, Experimental ; blood ; drug therapy ; Tumor Necrosis Factor-alpha ; blood

A 23-year-old man in remission from acute myeloblastic leukemia after allogeneic peripheral blood stem cell transplantation developed peripheral neuropathy presenting as sciatic and peroneal nerve deficits. Electrophysiological tests localized the lesions to the left sciatic and common peroneal nerve. Magnetic resonance imaging revealed nerve thickening and enhancement, while a positron emission tomography-computed tomography scan demonstrated increased fluorodeoxyglucose uptake tracking along the nerve, suggesting peripheral nerve infiltration. This report demonstrates an unusual presentation of acute leukemia relapse presenting as focal neuropathy

To investigate and step in the compliance of clinician hand hygiene, we used vari-ous management tools of the quality control circle (QCC), and then compared the change of the com-pliance before and after any operations. Firstly, we followed this 5 steps: selecting themes, drafting plans, grasping current situations, setting goals and analyzing objectives. Then, we formulated and im-plemented the interventions pertinently. All of the QCC members participated actively in the whole process. The compliance of clinician hand hygiene was improved from 41.11%to 57.59%. The realiza-tion rate was 115.97%, the progress rate was 40.99%, and the hand hygiene compliance of hand hy-giene in different time was significantly improved with the average value 1.25. Standardized result formed by quality control circle activity had a comprehensive promotion in the hospital and promoted the management of hospital infection and the development of hospital.

ObjectiveTo investigate the role of overexpressed proinflammatory cytokines in the pathogenesis of cerebral palsy (CP).MethodsLevels of tumor necrotic factor-α (TNF-α) and interleukin-6 (IL-6) in serum of 31 CP children, 20 healthy children (as controls), 37 neonates with CP risk factors such as hypoxic-ischemic injury and/or perinatal infection, and 20 healthy neonates (as controls) were measured by enzyme-linked immunosorbent assays (ELISA) retrospectively.ResultsLevels of TNF-α and IL-6 of CP children and neonates with CP risk factors were significantly higher than that of healthy controls (P<0.05). TNF-α level of CP children was significantly higher than that of neonates with CP risk factors (P<0.05), but there was no significant difference in IL-6 level between two groups.ConclusionOverexpressed proinflammatory cytokines play an important role in the pathogenesis of CP and may be an independent risk factor of CP.

A novel series of fingolimod analogues containing diphenyl ether moiety were designed and synthesized based on the modification of immunosuppressive agent fingolimod used in the treatment of multiple sclerosis. Compounds were evaluated in vivo for lymphopenic activity and heart rate affection. Most compounds showed moderate lymphopenic activity. It is worth noting that compounds 6c, 6d and 14c-14e showed considerable immunosuppressive activities comparable to fingolimod. And compound 14e had no effect on heart rate.
Animals ; Fingolimod Hydrochloride ; chemical synthesis ; pharmacology ; Heart Rate ; drug effects ; Immunosuppressive Agents ; chemistry ; Lymphopenia ; pathology ; Phenyl Ethers ; chemistry ; Structure-Activity Relationship

OBJECTIVETo investigate the influence of therapeutic bloodletting at Jing-well points and hypothermia on acute cerebral edema after traumatic brain injury (TBI) in rats.

METHODSSeventy-five SD rats were randomly divided into sham-operation group (Sham), TBI group (TBI), bloodletting group (BL), mild-induced hypothermia group (MIH), and bloodletting plus MIH group (BL + MIH) (n = 15). The model of TBI was established by electric controlled cortical impactor (eCCI). The rats of BL group were bloodletting at Jing-well points immediately after injury, twice daily. While the MIH group was settled on a hypothermia blanket promptly after TBI for 6 hours, so that the temperature dropped to 32 degrees. Each of measurement was performed after 48 hours. Magnetic resonance imaging (MRI) was used to evaluate the dynamic impairment of cerebral edema after TBI (n = 3). In addition, mNSS score, measurements of wet and dry brain weight, and Evans Blue assay were performed to investigate the neurologic deficit, cerebral water content (n = 8), and blood-brain barrier permeability (BBB), (n = 4), respectively.

RESULTSMRI analysis showed that the cerebral edema, hematoma and midline shifting of rats in TBI group was more serious than other treatment group. Meanwhile compared with TBI group, the mNSS scores of every treatment group were meaningfully lower (all P < 0.05). Furthermore, treatment with BL+ MIH group was superior to the separated BL and MIH group (all P < 0.01). In addition, brain water content of each intervention group reduced to varying degrees (all P < 0.05), especially that of MIH group and BL + MIH group (P <0.01). BBB permeability of each treatment group was also significantly improved (all P < 0.01), and the improvement in MIH group and BL + MIH group was much better than the BL alone group (P < 0.05, P < 0.01).

CONCLUSIONOur major finding is that bloodletting at Jing-well points and MIH can reduce cerebral edema and BBB dysfunction and exert neuroprotective effects after TBI. The results suggest that the combination of BL and MIH is more effective than other treatment being used alone.

Animals ; Blood-Brain Barrier ; Bloodletting ; Brain ; pathology ; Brain Edema ; prevention & control ; Brain Injuries ; therapy ; Hypothermia, Induced ; Rats ; Rats, Sprague-Dawley

Bronchogenic Cyst ; congenital ; diagnosis ; Child ; Diagnosis, Differential ; Female ; Humans ; Lung Diseases ; diagnosis