BACKGROUND: This study was undertaken to determine the effect of mesenchymal stem cells (MSCs) engraftment on vascular endothelial cell growth factor (VEGF) in lung tissue, plasma and extravascular lung water at early stage of smoke inhalation injury. METHODS: A rabbit smoke inhalation injury model was established using a home-made smoke inhalation injury generator, and rabbits were divided into two groups randomly: a control group (S group, n=32) and a MSCs treatment group (M group,n=32). 10 ml PBS was injected via the ear marginal vein immediately at injury into the S group. Third generation MSCs with a concentration of 1×107/10 ml PBS were injected via the ear marginal vein immediately at injury into the M group. VEGF in peripheral blood and lung tissue were measured at 0 (baseline), 2, 4 and 6 hours after injection respectively and analyzed. The right lungs of rabbits were taken to measure lung water mass fraction. RESULTS: In the lung tissue, VEGF decreased gradually in the S group (P<0.05) and signifi cantly decreased in the M group (P<0.05), but it increased more signifi cantly than the values at the corresponding time points (P<0.05). In peripheral blood, VEGF increased gradually in the S group (P<0.05) and markedly increased in the M group (P<0.05), but it decreased more signifi cantly than the values at corresponding time points (P<0.05). CONCLUSION: MSCs engraftment to smoke inhalation injury could increase VEGF in lung tissue, decrease VEGF in plasma and reduce extravascular lung water, indicating its protective effect on smoke inhalation injury.

OBJECTIVETo study the effect of bone marrow-derived mesenchymal stem cells (MSC) transplantation on the major inflammatory cytokines content in peripheral blood, lung water mass fraction, and lung tissue injury in rabbits with smoke inhalation injury.

METHODSSixteen adult New Zealand big ear rabbits were subjected to smoke inhalation injury and then were divided into pure injury group (PI, n = 8) and MSC transplantation group (MT, n = 8) according to the random number table. Via ear marginal vein, rabbits in PI group were injected with 10 mL phosphate buffered saline (PBS); rabbits in MT group were injected with 10 mL PBS containing the third passage MSC (1 x 10⁷ cell) isolated from marrow of healthy young New Zealand big ear rabbit. Another 8 rabbits were enrolled as normal control group (NC). Rabbits in NC group were injected with 10 mL PBS via ear marginal vein without smoke inhalation injury. Blood was harvested from rabbits in PI and MT groups at post injury hour (PIH) 2, 4, 6. Contents of TNF-α, IL-1β, IL-6, and IL-10 in serum were determined with ELISA. At PIH 24, left lung was harvested for morphology and histopathology observation; the right lung tissue was obtained to measure and calculate lung water mass fraction. Blood and lung tissue of rabbits in NC group were harvested and determined in the same way. Data were processed with t test.

RESULTS(1) Serum contents of TNF-α in PI and MT groups at each time point were obviously higher than that in NC group (t = 2.43 - 9.57, P < 0.05 or P < 0.01). Serum contents of IL-1β and IL-6 in PI group at each time point were obviously higher than those in NC group (t = 8.49 - 19.80, P values all below 0.01). Serum content of IL-1β in MT group at each time point was close to that in NC group (t = 0.11 - 0.92, P values all above 0.05). Serum content of IL-6 in MT group at PIH 2 was close to that in NC group (t = 2.12, P > 0.05), but that of MT group increased significantly at PIH 4 and 6 (t = 2.83, P values all below 0.05). Serum contents of TNF-α, IL-1β, and IL-6 in MT group at each time point were obviously lower than those in PI group (t = 2.35 - 12.45, P < 0.05 or P < 0.01). (2) Serum content of IL-10 in MT group at PIH 2, 4, and 6 was respectively (13.0 ± 3.6), (11.6 ± 8.5), (15.2 ± 4.4) pg/mL, and they were higher than those in PI group [(5.5 ± 3.4), (5.0 ± 1.7), (7.9 ± 3.5) pg/mL, with t value respectively 4.28, 2.15, 3.67, P values all below 0.01]. Serum contents of IL-10 in PI and MT groups were obviously higher than that in NC group (t = 2.46-8.14, P < 0.05 or P < 0.01). (3) Lung tissue injury in MT group was alleviated markedly as compared with that in PI group. (4) At PIH 24, lung water mass fraction in MT group was (69 ± 7)%, which was obviously lower than that in PI group [(87 ± 6)%, t = 5.49, P < 0.01]. Compared with that in NC group [(48 ± 3)%], lung water mass fraction in PI and MT groups were increased obviously (with t value respectively 16.93 and 7.22, P values all below 0.01).

CONCLUSIONSMSC transplantation can decrease pro-inflammatory cytokines, increase anti-inflammatory cytokines, decrease lung water mass fraction, ameliorate systemic inflammatory response, and protect lung tissue in rabbits with smoke inhalation injury.

Animals ; Bone Marrow Cells ; cytology ; Inflammation ; Interleukin-10 ; blood ; Interleukin-6 ; blood ; Lung Injury ; blood ; surgery ; Mesenchymal Stem Cell Transplantation ; Rabbits ; Smoke Inhalation Injury ; blood ; surgery ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo investigate the changes in the serum content of immunoreactive calcitonin (iCT) after burns or inhalation injury, and to explore its diagnostic significance.

METHODSTwenty-four dogs were randomized into 4 groups, i. e. A (n = 6, with moderate degree inhalation injury) , B ( n = 6, with severe inhalation injury), C (n = 6, with most severe inhalation injury) and D (n = 6, with severe burns) groups. The serum content of iCT and blood gas analysis before and after injury were determined at different time points. The degree of inhalation injury was determined with fibrobronchoscopic examination at 6 post-inhalation injury hour (PIH).

RESULTS(1) Fiber bronchoscopic examination showed that the degree of inhalation injury in each group was coincident with the anticipation. (2) The serum content of iCT in each group at 1 PIH was obviously higher than that before injury, and it was evidently higher in A, B and C groups than that in D group at 4 PIH. The peak value of iCT in group A at 24 PIH was (453+/-224) ng/L, and it increased gradually in B and C groups at 48 PIH. The serum content of iCT increased continually from 2 PIH on, and it reached (125+/-41) ng/L at 48 PIH. (3) Compared with PaO2 value before injury (109+/-8) mmHg, there was no obvious difference of the PaO, in A and D groups. PaO2 value in B and C group began to descend continually at 8 PIH (65+/-6) mmHg, and that in C group began to descend at 4 PIH (71+/-9) mmHg. PaCO2 value in C group began to increase at 24 PIH(52+/-11) mmHg when compared with that before injury(38+/-5 ) mmHg.

CONCLUSIONThe changes in the serum level of iCT within 8 PIH occurred much earlier than PaO2 and PaCO2, thus it has the same diagnostic significance as fibers bronchoscopic examination.

Animals ; Blood Gas Analysis ; Burns, Inhalation ; blood ; physiopathology ; Calcitonin ; blood ; Disease Models, Animal ; Dogs

OBJECTIVETo analyze microarray datasets deposited in the public database and to identify TNM associated genes in gastric cancers.

METHODSMicroarray datasets of gastric cancer were selected from GEO database. Differentially expressed genes related to TNM staging were evaluated by significant analysis of the microarray using MultiExperiment Viewer (MEV) platform. Candidate gene expressions in gastric cancer tissues and cell lines were verified by reverse transcriptase polymerase chain reaction (RT-PCR), quantitative RT-PCR, Western blot and immunohistochemistry.

RESULTSGES4007 dataset was re-analyzed leading to the identification of 14 genes associated with TNM staging. Over-expression of matrix gla protein (MGP) was confirmed in gastric cancer cell lines and tumor tissues by quantitative RT-PCR, Western blot and immunohistochemistry. Increased MGP expression was found in 22 of 54 cases of (40.7%) gastric cancer specimens compared to the normal gastric tissues. The up-regulation of MGP mRNA expression closely correlated with TNM stage (P = 0.001) and prognosis (P = 0.006).

CONCLUSIONSPublic databases of microarray studies are the valuable resources for data mining. MGP has been identified and confirmed as a novel biomarker for the TNM stage and prognosis of gastric cancer.

Adult ; Aged ; Biomarkers, Tumor ; genetics ; metabolism ; Calcium-Binding Proteins ; biosynthesis ; genetics ; Cell Line, Tumor ; Extracellular Matrix Proteins ; biosynthesis ; genetics ; Female ; Follow-Up Studies ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Oligonucleotide Array Sequence Analysis ; RNA, Messenger ; metabolism ; Stomach Neoplasms ; genetics ; metabolism ; pathology ; Survival Rate ; Up-Regulation ; Young Adult

AIMA series of triazole antifungals were synthesized to search for novel triazole antifungals with more potent activity, less toxicity and broader spectrum.

METHODSNineteen 1-(1,2,4-triazolyl-1H-1-yl)-2-(2,4-diflurophenyl)-3-(4-substituted benzyl-1-piperazinyl)-2-propanols were designed and synthesized, on basis of the three dimensional structure of P450 cytochrome 14 alpha-sterol demethylase (CYP51) and their antifungal activities were also evaluated.

RESULTSAll the title compounds were first reported. Results of preliminary biological tests showed that most of the title compounds exhibited high activity against the eight common pathogenic fungi and the activities against deep fungi were higher than that against shallow fungi.

CONCLUSIONMost of the title compounds showed higher antifungal activities than Fluconazole and Terbinafine. Compound VIII-1, 10, 12, 17 showed best antifungal activity with broad antifungal spectrum and were chosen for further development.

Antifungal Agents ; chemical synthesis ; chemistry ; pharmacology ; Aspergillus fumigatus ; drug effects ; Candida albicans ; drug effects ; Cryptococcus neoformans ; drug effects ; Microbial Sensitivity Tests ; Molecular Structure ; Triazoles ; chemical synthesis ; chemistry ; pharmacology

OBJECTIVETo observe the homing and differentiation of marrow-derived mesenchymal stem cells (MSC) transplanted intravenously in smoke inhalation injured rabbits.

METHODSThirty-two New Zealand big ear rabbits were divided into normal control group (NC), inhalation injury group (II), normal control + MSC treatment group (NM), and MSC treatment group (MT) according to the random number table, with 8 rabbits in each group. Rabbits in NC group were injected with 10 mL phosphate buffered saline (PBS) via ear marginal vein. Rabbits in NM group were injected with 10 mL PBS containing the third generation MSC labeled by BrdU (1 × 10(7) per 10 mL PBS) via ear marginal vein. Severe smoke inhalation injury model was reproduced in the other two groups, among them rabbits in II group were treated as rabbits in NC group, rabbits in MT group treated as rabbits in NM group. On the 7th and 28th day post treatment (PTD), lung tissue and trachea tissue were harvested from four groups for observation on injury with HE staining. Homing of MSC in injured tissue was observed with immunohistochemistry staining. The differentiation of MSC into functional cells was observed with immunohistochemical double staining of combining nuclear marker BrdU with lung (trachea) membrane-specific marker aquaporin-5 (AQP-5), alkaline phosphatase (AKP), CD34, and cytokeratin respectively.

RESULTS(1) MSC homing in lung and trachea tissue was observed in MT group on PTD 7, which was not observed in NM group. (2) AQP-5, AKP, and CD34 positive MSC were observed in lung tissue in MT group on PTD 28, while cytokeratin positive MSC was not observed in trachea tissue. No positively marked MSC was observed in NM group. (3) Injury in lung and trachea was less severe in MT group than in II group; and the proliferation of fibroblasts was less in MT group.

CONCLUSIONSIntravenous injection of MSC to rabbits with smoke inhalation injury can migrate to lung and trachea tissue at obviously inflammatory site, and differentiate into alveolar epithelial cells typeI and II, and pulmonary vascular endothelial cells, which may participate in the process of tissue repair in smoke inhalation injury.

Animals ; Bone Marrow Cells ; cytology ; Cell Differentiation ; Cells, Cultured ; Endothelial Cells ; cytology ; Epithelial Cells ; cytology ; Lung ; cytology ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; cytology ; Pulmonary Alveoli ; cytology ; Rabbits ; Smoke Inhalation Injury ; pathology ; Trachea ; cytology

OBJECTIVETo study the effects of high frequency oscillatory ventilation (HFOV) combined with incremental positive end-expiratory pressure (IP) on respiratory and circulatory functions, and lung histopathology of dogs with smoke inhalation injury.

METHODSAfter being treated with conventional mechanical ventilation, 12 dogs were inflicted with severe smoke inhalation injury and divided into group HFOV and group HFOV+IP according to the random number table, with 6 dogs in each group. Then they received corresponding ventilation for 8 hours respectively. Blood gas analysis results (pH value, PaO2 and PaCO2 levels) and hemodynamic parameters [heart rate, mean arterial pressure (MAP), pulmonary arterial pressure (PAP), central venous pressure (CVP), cardiac output (CO)] were recorded before injury, immediately after injury, and at post ventilation hour (PVH) 2, 4, 6, and 8. The dogs of two groups were sacrificed at PVH 8. A healthy dog without any treatment and a dog with smoke inhalation injury but no subsequent treatment were sacrificed in addition. Lung tissues of all dogs were obtained for histopathological observation. Lung injury score examination was conducted in both groups. Data were processed with rank sum test, analysis of variance of repeated measurement, and LSD- t test.

RESULTS(1) The PaO2 levels in both groups were significantly decreased immediately after injury, compared with those before injury (with t values respectively 4.960, 5.310, P values all below 0.01). The PaO2 levels in both groups from PVH 2 to PVH 8 were significantly increased, compared with those observed immediately after injury (with t values from 4.930 to 6.050, P values all below 0.01). At PVH 2, 4, and 8, PaO2 levels in group HFOV+IP were significantly higher than those in group HFOV (with t values from 3.775 to 5.774, P values all below 0.01); no statistically significant differences were observed in pH value and PaCO2 level at each time point between two groups (with t values from 0.002 to 0.997, P values all above 0.05). (2) There were no statistically significant differences in MAP, PAP, and CVP within two groups at each time point (with F values from 1.316 to 4.959, P values all above 0.05). In group HFOV, heart rate from PVH 2 to PVH 8 was significantly lower than that observed immediately after injury (with t values from 3.780 to 8.970, P values all below 0.01). In group HFOV+IP, CO at PVH 4, 6, and 8 was significantly lower than that observed immediately after injury (with t values from 3.990 to 11.200, P values all below 0.01). There were no statistically significant differences in MAP, PAP, and CVP between two groups at the same time point (with t values from 0.089 to 2.123, P values all above 0.05). At PVH 4, 6, and 8, heart rate in group HFOV+IP was higher than that in group HFOV (with t values from 2.931 to 7.229, P < 0.05 or P < 0.01), while CO was lower (with t values from 4.297 to 11.206, P values all below 0.01). (3) Compared with those of the healthy dog, inflammatory cell infiltration and bleeding in the lung were observed in alveolar space in both group HFOV and group HFOV+IP, while the degree was less serious than that of the dog with smoke inhalation injury only. Compared with those of group HFOV, inflammatory cell infiltration in group HFOV+IP was less significant, the alveolar structure was relatively intact, and no thickening of alveolar walls was observed. The lung injury score in group HFOV [(3.27 ± 0.24) points] was higher than that of group HFOV+IP [(2.79 ± 0.31) points, t = 27, P < 0.05].

CONCLUSIONSHFOV combined with IP can improve gas exchange and alleviate pulmonary injury without any adverse effect on blood gas analysis or hemodynamic parameters. Therefore, it may be considered as an appropriate mode of ventilation for the treatment of smoke inhalation injury.

Animals ; Blood Gas Analysis ; Burns, Inhalation ; physiopathology ; therapy ; Disease Models, Animal ; Dogs ; Hemodynamics ; High-Frequency Ventilation ; Male ; Positive-Pressure Respiration ; Smoke ; adverse effects

OBJECTIVETo study the difference of the gene expression profile and to identify the different expression after transfection of the ARL-1 gene.

METHODSThe cDNA probes were synthesized from total RNA of study group and control group, which was differentially hybridized to cDNA chips and confirmed by a gene specific semiquantitative reverse transcription polymerase chain reaction (RT-PCR).

RESULTSSix kinds of gene expression were increased and 9 kinds of gene expression were decreased. The findings were correlated with protein metabolism, signal pathway, metastasis, and drug resistance.

CONCLUSIONScDNA chips showed that gene expression profile of liver carcinoma cell was changed after transfection of the ARL-1 gene. It is a useful method in understanding the mechanism of drug resistance.

Aldehyde Reductase ; genetics ; Drug Resistance, Neoplasm ; Gene Expression Profiling ; Humans ; Liver Neoplasms ; drug therapy ; genetics ; Oligonucleotide Array Sequence Analysis ; Transfection

The constituents in 95% ethanol extract of the root of Rosa cymosa Tratt were purified by column chromatography techniques, leading to isolation of eleven triterpenes. Their structures were elucidated by spectroscopic data as pomolic acid (1), fupenzic acid (2), ursolic acid (3), euscaphic acid (4), arjunic acid (5), tomentic acid (6), 3β-E-feruloyl corosolic acid (7), 1β-hydroxyeuscaphic acid (8), myrianthic acid (9), cecropiacic acid (10), and ilexoside B (11). Among them, compounds 3, 6-8, 10 and 11 were obtained from this plant for the first time, and compounds 7 and 10 were obtained from this genus for the first time.
Drugs, Chinese Herbal ; chemistry ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Plant Roots ; chemistry ; Rosa ; chemistry ; Triterpenes ; chemistry

OBJECTIVETo evaluate the efficacy of Bufei Yishen Granule BFYSG) combined with Shufei Tie acupoint sticking therapy on quality of life of patients with stable chronic obstructive pulmonary disease (COPD).

METHODSA multi-center, double-blinded, double-dummy and randomized controlled method was adopted in this trial. A total of 244 patients were randomly assigned to a trial group and a control group according to the random number, each with 122 patients; treatment allocation occurred when the participants met the inclusion criteria and signed the informed consent form. In the trial group, patients were treated with BFYSG combined with "Shufei Tie" acupoint sticking therapy and sustained-release theophylline dummy, and in the control group patients were treated with oral sustained-release theophylline and BFYSG dummy combined with "Shufei Tie" acupoint sticking therapy dummy. The therapeutic course for two groups was 4 months and the follow-up was 6 months. The frequency and duration of acute exacerbation calculated by adding up each frequency and duration of acute exacerbation in treatment and follow-up time respectively, the quality of life measured by the World Health Organization Quality of Life (WHOQOL)-BREF scale and adult COPD quality of life (COPD-QOL) scale were observed.

RESULTSAmong the 244 enrolled patients, 234 were screened for full analysis set (FAS); 221 were screened for per-protocol analysis set (PPS). After 4-month treatment and 6-month follow-up there were differences between the trial group and the control group in frequency of acute exacerbation (FAS: P=0.013; PPS: P=0.046); duration of acute exacerbation (FAS: P=0.005; PPS: P=0.006); scores of physiological, psychological and environment aspects of the WHOQOL-BREF questionnaire (FAS: P=0.002, P=0.006, P=0.000; PPS: P=0.00, P=0.001, P=0.000); scores of daily living ability, social activity, depression symptoms aspects of the COPD-QOL questionnaire (FAS: P=0.000, P=0.000, P=0.006; PPS: P=0.002, P=0.001, P=0.001).

CONCLUSIONBFYSG combined with acupoint sticking therapy could improve the quality of life of patients with stable COPD.

Acupuncture Points ; Adult ; Aged ; Anxiety ; complications ; psychology ; Combined Modality Therapy ; Depression ; complications ; psychology ; Disease Progression ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Pulmonary Disease, Chronic Obstructive ; complications ; drug therapy ; psychology ; Quality of Life ; Surveys and Questionnaires ; Treatment Outcome