H19 Overexpression Improved Efficacy of Mesenchymal Stem Cells in Ulcerative Colitis by Modulating the miR-141/ICAM-1 and miR-139/CXCR4 Axes.

Overexpression of C-X-C motif chemokine receptor 4 (CXCR4) and intercellular cell adhesion molecule-1 (ICAM-1) may promote homing of mesenchymal stem cells (MSC). In this study, we treated ulcerative colitis animals with MSC preconditioned with or without H19 and compared the therapeutic effect of MSC and MSC-H19. We evaluated the regulatory relationship of H19 vs. miR-141/miR-139 and miR-141/miR-139 vs. ICAM-1/CXCR4. We established an ulcerative colitis mouse model to assess the effect of MSC and MSC-H19. H19 was found to bind to miR-141 and miR-139. The activity of H19 was strongly decreased in cells c-transfected with miR-141/miR-139 and WT H19. ICAM-1 was confirmed to be targeted by miR-141 and CXCR4 was targeted by miR-139. The H19 expression showed a negative regulatory relationship with the miR-141 and miR-139 expression but a positive regulatory relationship with the ICAM-1 and CXCR4 expression. In summary, the overexpression of H19 in MSC downregulated miR-139 and miR-141, thus increasing the activity of their targets ICAM-1 and CXCR4, respectively, to exhibit therapeutic effects in ulcerative colitis.

Psychophysiological and cognitive effects of strawberry plants on people in isolated environments / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

In manned deep-space exploration, extremely isolated environments may adversely affect the mood and cognition of astronauts. Horticultural plants and activities have been proven to be effective in improving their physical, psychological, and cognitive states. To assess the effects of applying horticultural plants and activities in isolated environments, this study investigated the influence of viewing strawberry plants on the mood of people in a laboratory experiment as indicated by heart rate, salivary cortisol, and psychological scales. The results showed that heart rate and salivary cortisol were significantly decreased after viewing strawberry plants for 15 min. "Tension" and "confusion" scored using the Profile of Mood States negative mood subscales, and anxiety levels measured using the State-Trait Anxiety Inventory scale were also significantly reduced. This study further explored the impact of viewing strawberry plants on cognition. A notable reduction of the subjects' reaction time after 15-min plant viewing was observed. Based on these findings, a long-duration isolated experiment in a bioregenerative life support system-"Lunar Palace I"-was conducted. A similar trend was obtained that crew members' mood states were improved by viewing the strawberry plants, but no significant change was observed. This study provided some experimental evidence for the benefits of interacting with strawberry plants in isolated environments.

[Sericin regulates proliferation of human gastric cancer MKN45 cells through autophagic pathway].

OBJECTIVE: To investigate the effect of sericin on the proliferation of human gastric cancer MKN45 cells and explore the underlying molecular mechanism. METHODS: MKN45 cells were transfected by LC3 double fluorescent autophagic virus, and the positive cells screened by puromycin were divided into blank group, sericin group and sericin∓3-MA group. After incubation with sericin for 48 h, the cells were examined for proliferation, apoptosis and cell cycle using CCK-8 assay and flow cytometry. Cell autophagy was detected by transmission electron microscopy (TEM) and fluorescent inverted microscope, and the autophagy-related markers including LC3, p62 and Beclin proteins were detected with Western blotting. Nude mice bearing gastric cancer xenograft were treated with normal saline or sericin injections (n=5) and the changes in the tumor volume and weight were measured. RESULTS: Compared with the blank group, MKN45 cells with sericin treatment showed significantly inhibited proliferation both in vitro and in nude mice. Autophagosomes were observed in sericin-treated cells under TEM and fluorescent inverted microscope. Sericin treatment of the cells significantly increased the cell apoptosis (P<0.01), caused obvious cell cycle arrest in G2/M phase (P<0.01), up-regulated the expressions of both LC3-2 and Beclin, and down-regulated the expression of p62. The autophagy inhibitor 3-MA obviously antagonized the effects of sericin on cell apoptosis, cell cycle and autophagic protein expressions. CONCLUSION: Sericin can inhibit the proliferation of human gastric cancer MKN45 cells by regulating cell autophagy to serve as potential anti-tumor agent.

Histones and chymotrypsin-like elastases play significant roles in the antimicrobial activity of tongue sole neutrophil extracellular traps.

Neutrophil extracellular traps (NETs) are a form of extracellular antimicrobial structure of neutrophils observed in higher and lower vertebrates, the latter including the teleost fish tongue sole Cynoglossus semilaevis. However, the antimicrobial mechanism of fish NETs is unknown. In the present study, we examined the potential contribution of histones and elastases to the antibacterial effect of tongue sole NETs. For this purpose, two histones (CsH2B and CsH4) and two elastases (CsEla1 and CsEla2) of tongue sole were investigated. The histones and elastases possess the conserved domain structures characteristic of that of histones H2B/H4 and trypsin-like serine protease, respectively. Recombinant CsH2B, CsH4, CsEla1, and CsEla2 bound a wide range of Gram-negative and Gram-positive bacteria, and some of the bound bacteria were inhibited in growth by the bound histones/elastases. CsH2B, CsH4, CsEla1, and CsEla2 were all localized in NETs induced by various stimuli including bacterial pathogen. Treatment of NETs with antibodies targeting CsH2B, CsH4, CsEla1, and CsEla2 significantly reduced the antimicrobial effect of NETs. These results indicate that histones and chymotrypsin-like elastases are fundamental components of teleost NETs that play important roles in the antimicrobial activity of NETs.

Neutrophil Extracellular Traps of Cynoglossus semilaevis: Production Characteristics and Antibacterial Effect.

Neutrophil extracellular traps (NETs) are structures released by neutrophils as a cellular immune defense against microbial invasion. The process of NETs generation, netosis (NETosis), can take place via either a suicidal mechanism, during which the NETs-releasing cells became dead, or a "live" mechanism, during which the NETs-releasing cells remain vital. NETosis has been studied intensively in mammals in recent years, but very little is known about the NETosis in fish. In this study, we examined NETosis in tongue sole (Cynoglossus semilaevis), a species of teleost with important economic values. We found that following stimulation with phorbol 12-myristate 13-acetate (PMA) and three common fish bacterial pathogens, abundant NETs structures were released by neutrophils that were most likely in a live state. The released NETs captured, but did not kill, the bacterial pathogens; however, the replication of extracellular, but not intracellular, pathogens was inhibited by NETs to significant extents. Reactive oxygen species (ROS), nitric oxide (NO), and myeloperoxidase (MPO) production were observed to be enhanced in NETosing neutrophils, and blocking the production of these factors by inhibitors significantly decreased NETs production induced by PMA and all three bacteria. Taken together, these results indicate for the first time that in teleost there exists a non-cell death pathway of NETosis that produces NETs with antibacterial effects in a ROS-, NO-, and MPO-dependent manner.

[Clinical observation of early oral enteral nutrition after laparoscopic colectomy].

OBJECTIVE: To investigate the effect and safety of two types of early enteral nutrition, total protein(TP) and total protein with fibers(TPF-FOS), after laparoscopic colectomy. METHODS: Patients with colon cancer were divided into TP group and TPF-FOS group. Oral nutrition was given from the first postoperative day. Hemoglobin, albumin, prealbumin, white blood cell count, C-reactive protein, procalcitonin were tested before operation and on the first and seventh postoperative day. The time to first flatus, time to first bowel movement, fever, infection, and diarrhea were observed after operation. RESULTS: No significant difference was observed in hemoglobin, albumin, prealbumin, white blood cell count, C-reactive protein, and procalcitonin between these two groups. Higher proportion of patients defecated formed stool during the observation in TPF-FOS group(76.7% vs. 27.3%, P<0.01). Less abdominal bloating was found from the fourth to the seventh postoperative day in TPF-FOS group (5.8% vs. 15.2%, P<0.05). CONCLUSIONS: Both TP and TPF-FOS can be safely used for early oral enteral nutrition after laparoscopic colectomy. TPF-FOS may be more beneficial to the recovery of gastrointestinal function.

Inhibitory effects of mild hyperthermia plus docetaxel therapy on ER(+/-) breast cancer cells and action mechanisms / 华中科技大学学报（医学）（英德文版）

The purpose of this study was to verify that a combination of mild hyperthermia and docetaxel chemotherapy produces synergistic antitumor effects and to explore the action mechanisms of this treatment approach. The effects of docetaxel on the proliferation of cells from the estrogen receptor (ER)-positive human breast cancer cell line MCF-7 and the ER-negative human breast cancer cell line MDA-MB-453 were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and effective experimental concentrations of docetaxel were determined. The effects of mild hyperthermia plus docetaxel therapy on apoptosis rate in the MCF-7 and MDA-MB-453 human breast cancer cell lines were analyzed by using flow cytometry with Annexin-V fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining. The effects of these combined treatments on cell cycle progression in the MCF-7 and MDA-MB-453 human breast cancer cell lines were examined by using flow cytometry. The effects of these combined treatments on the expression of apoptosis-related proteins and proteins in the mitogen-activated protein kinase (MAPK) pathways were analyzed by using Western blotting. The effects of these combined treatments on the expression of the heat shock protein 70 (HSP70) and the multi-drug resistance (MDR) gene product P-glycoprotein (Pgp) were examined by using Western blotting. The results showed that the half-maximal inhibitory concentration (IC50) of docetaxel for MCF-7 and MDA-MB-453 cells was 19.57±1.12 and 21.64±2.31 μmol/L respectively. Mild hyperthermia with docetaxel therapy could increase apoptosis rate in the MCF-7 and MDA-MB-453 cells. Apoptosis rate in MCF-7 and MDA-MB-453 cells was increased from (23.66±3.59)% and (18.51±3.17)% in docetaxel treatment group to (47.12±6.73)% and (55.16±7.42)% in mild hyperthermia plus docetaxel group, indicating that the mild hyperthermia and docetaxel therapeutic approaches exhibited significant synergistic antitumor effects. Treatments of mild hyperthermia plus docetaxel induced G2/M cell cycle arrest in the MCF-7 and MDA-MB-453 cells. Western blotting demonstrated that proteins in the MAPK pathway were expressed at higher levels in docetaxel-treated cells following mild hypothermia than those in cells treated with docetaxel alone. As compared with blank control group, cells from the mild hyperthermia plus docetaxel group exhibited significantly decreased B-cell lymphoma 2 (Bcl-2) protein expression but slightly increased Bcl-2-associated X protein (Bax) expression. Western blotting results revealed that HSP70 and Pgp expression levels were significantly increased following mild hypothermia. It was concluded that treatments of mild hyperthermia plus docetaxel inhibited the proliferation of human breast cancer cells, promoted apoptosis of breast cancer cells, and produced synergistic antitumor effects.

Inhibitory effects of mild hyperthermia plus docetaxel therapy on ER(+/-) breast cancer cells and action mechanisms / 华中科技大学学报（医学）（英德文版）

The purpose of this study was to verify that a combination of mild hyperthermia and docetaxel chemotherapy produces synergistic antitumor effects and to explore the action mechanisms of this treatment approach. The effects of docetaxel on the proliferation of cells from the estrogen receptor (ER)-positive human breast cancer cell line MCF-7 and the ER-negative human breast cancer cell line MDA-MB-453 were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and effective experimental concentrations of docetaxel were determined. The effects of mild hyperthermia plus docetaxel therapy on apoptosis rate in the MCF-7 and MDA-MB-453 human breast cancer cell lines were analyzed by using flow cytometry with Annexin-V fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining. The effects of these combined treatments on cell cycle progression in the MCF-7 and MDA-MB-453 human breast cancer cell lines were examined by using flow cytometry. The effects of these combined treatments on the expression of apoptosis-related proteins and proteins in the mitogen-activated protein kinase (MAPK) pathways were analyzed by using Western blotting. The effects of these combined treatments on the expression of the heat shock protein 70 (HSP70) and the multi-drug resistance (MDR) gene product P-glycoprotein (Pgp) were examined by using Western blotting. The results showed that the half-maximal inhibitory concentration (IC50) of docetaxel for MCF-7 and MDA-MB-453 cells was 19.57±1.12 and 21.64±2.31 μmol/L respectively. Mild hyperthermia with docetaxel therapy could increase apoptosis rate in the MCF-7 and MDA-MB-453 cells. Apoptosis rate in MCF-7 and MDA-MB-453 cells was increased from (23.66±3.59)% and (18.51±3.17)% in docetaxel treatment group to (47.12±6.73)% and (55.16±7.42)% in mild hyperthermia plus docetaxel group, indicating that the mild hyperthermia and docetaxel therapeutic approaches exhibited significant synergistic antitumor effects. Treatments of mild hyperthermia plus docetaxel induced G2/M cell cycle arrest in the MCF-7 and MDA-MB-453 cells. Western blotting demonstrated that proteins in the MAPK pathway were expressed at higher levels in docetaxel-treated cells following mild hypothermia than those in cells treated with docetaxel alone. As compared with blank control group, cells from the mild hyperthermia plus docetaxel group exhibited significantly decreased B-cell lymphoma 2 (Bcl-2) protein expression but slightly increased Bcl-2-associated X protein (Bax) expression. Western blotting results revealed that HSP70 and Pgp expression levels were significantly increased following mild hypothermia. It was concluded that treatments of mild hyperthermia plus docetaxel inhibited the proliferation of human breast cancer cells, promoted apoptosis of breast cancer cells, and produced synergistic antitumor effects.

An efficient and convenient formal synthesis of Jaspine B from D-xylose.

A formal synthesis of Jaspine B was completed in 42.4% overall yield with only three purification steps (one by crystallization and two by column chromatography). The key step in the synthesis involves a regio- and stereoselective epoxide ring-opening reaction and the configuration inversion of the C3-hydroxyl group through oxidation and reduction. All of the reagents and materials used were quite common and inexpensive.

Prevalence of abnormity of blood lipid and associated factors in health examination population in Beijing.

OBJECTIVE: To investigate the prevalence of abnormity of blood lipid and associated factors in healthy population in Beijing. METHODS: Totally, 38462 individuals who received health examination were enrolled in our study. We divided them into eight groups according to their ages. The levels of serum total cholesterol, triglyceride, high density lipoprotein cholesterol, and low density lipoprotein cholesterol were tested, and the relationship of blood lipid abnormity with body mass index (BMI) and fasting blood glucose was analyzed. RESULTS: The incidences of hypercholesterolemia, hyperglyceridemia, low high-density lipoprotein cholesterolemia, and hyper low-density lipoprotein cholesterolemia presented increasing trend in this population. The incidence rate of abnormity of blood lipid in health examination population increased with BMI increase. The incidence of abnormity of blood lipid in overweight and obesity population was significantly higher than that in low weight and normal weight populations (P<0.05). Meanwhile, the trend of abnormal blood lipid incidence coincided with that of abnormal fasting blood glucose. CONCLUSIONS: The prevalence of overweight, obesity, and abnormity of blood lipid in Beijing presents increasing trend. The incidence of abnormity of blood lipid increases with BMI increase, in coincidence with that of fasting blood glucose.

Overexpression of hSav1 promotes Mst1-induced apoptosis in HeLa cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To elucidate the effect of hSav1 expression on Mst1-mediated apoptosis in HeLa cells.</p><p><b>METHODS</b>Plasmids pCMV-HA-hSav1 and pcDNA/4TO-Flag-Mst1 were constructed and cotransfected into HeLa cells. Triple immunofluorescent labeling of hSav1, Mst1 and nucleus was performed to determine their subcellular localization. Plasmids pCMV-HA-hSav1 and/or pcDNA/4TO-Flag-Mst1 were transfected into HeLa cells, and 36 hours later cisplatin (50 micromol/L) as a pro-apoptotic agent was added for 14 hours. Cell apoptosis was analyzed by annexin V/PI assay.</p><p><b>RESULTS</b>Plasmids pCMV-HA-hSav1 and pcDNA/4TO-Flag-Mst1 were constructed and the authenticity of constructs was verified by sequencing. The binding in vitro showed that hSav1 could be detect from the anti-Mst1 immunoprecipitation complex. The immunofluorescent labeling showed that hSav1 and Mst1 had the same localization in cells. Overexpressed protein hSav1 did not induce a significant cell apoptosis. However, co-expression of hSav1 with Mst1 resulted in a significant increase of apoptosis above the level seen with Mst1 alone (24.5% +/- 2.4% vs. 39.3% +/- 4.0%, P < 0.05).</p><p><b>CONCLUSION</b>Our findings indicate that hSav1 is a newly identified protein that interacts with Mst1 and augments Mst1-mediated apoptosis.</p>