Changes of G cells and D cells in the antral mucosa in rat experimental gastric ulcer

Objective: To investigate the association of changes in G and D cells in the antral mucosa with the production of gastrin and somatostatin during gastric ulcer and the healing process. Methods: Experimental gastric ulcer was induced with acetic acid in 42 Wistar rats and another 7 normal rats served as control. Changes in the production of gastrin and somatostatin in the plasma, gastric fluid and the antral tissues of the rats were measured by radio immunoassay, and the number and distribution of G and D cells were respectively determined by immunochemistry and Quantimet500 image analysis system. Results: In rats with gastric ulcer, the gastrin levels in the plasma, gastric fluid and the antral tissues increased while somatostatin levels were reduced, which were corrected in the healing process. Immunochemistry demonstrated the increase in the number of G cells in the antral tissues with decrease in D cell number, and the area covered by both cells shrank. The G cell to D cell number and area ratios were both decreased after the onset of the ulcer and returned to the normal when the healing process took place. Conclusion; Secretion of gastrin by G cells increases and that of somatostatin by D cells declines during gastric ulcer in rats, and imbalance of G and D cells may be responsible for gastrointestinal dysfunction.

Gastrin and antral G cells in course of Helicobacter pylori eradication: Six months follow up study

AIM： To assess long-term effects of Helicobacter pylori （H pylon} eradication on antral G cell morphology and function in patients with and without duodenal ulcer （DU）.METHODS： Consecutive dyspeptic patients referred to the endoscopy entered the study. Out of 39 Hpylori positive patients, 8 had DU （Hpylori ＋DU） and 31 gastritis （Hpylori＋G）. Control groups consisted of 11 uninfected dyspeptic patients （CG1） and 7 healthy volunteers （CG2）. Basal plasma gastrin （PGL）, antral tissue gastrin concentrations （ATGC）, immunohistochemical and electron microscopic characteristics of G cells were determined, prior to and 6 mo after therapy.RESULTS： We-demonstrated elevated PGL in infected patients compared to uninfected controls prior to therapy.Elevated PGL were registered in all Hpylori＋patients （Hpylori＋DU： 106.78＋22.72 pg/mL, Hpylori＋G： 74.95＋15.63,CGI： 68.59＋17.97, CG2：39.24＋5.59 pg/mL, P〈0.01）.Successful eradication （e） therapy in Hpylori＋patients lead to significant decrease in PGL （Hpylori＋DU： 59.93＋9.40 and Hpylori＋Ge： 42.36＋10.28 pg/mL, P〈0.001）. ATGC at the beginning of the study were similar in infected and uninfected patients and eradication therapy lead to significant decrease in ATGC in Hpylori＋gastritis, but not in DU patients. In the Hpylori＋DU patients, the mean number of antral G cells was significantly lower in comparison with all other groups （P〈0.01）, but after successful eradication was close to normal values found in controls. By contrast, G cell number and volume density were significantly decreased （P〈0.01） in Hpylori＋Ge group after successful eradication therapy （294＋32 and 0.31＋0.02,respectively）, in comparison to values before eradication （416~40 and 0.48~0.09）. No significant change of the G cell/total endocrine cell ratio was observed during the 6 mo of follow up in any of the groups. A reversible increase in G cell secretory function was seen in all infected individuals, demonstrated by a more prominent secretory apparatus. However, differences between DU and gastritis group were identified.CONCLUSION： H py/oriinfection induces antral G cell hyperfunction resulting in increased gastrin synthesis and secretion. After eradication therapy complete morphological and functional recovery is observed in patients with gastritis. In the DU patients some other factors unrelated to the Hpyloriinfection influence antral G cell morphology and function.

Gastrointestinal hormone abnormalities and G and D cells in functional dyspepsia patients with gastric dysmotility

AIM: To investigate the relationship between gastric dysmotility,gastrointestinal hormone abnormalities, and neuroendocrine cells in gastrointestinal mucosa in patients with functional dyspepsia (FD).METHODS: Gastric emptying was assessed with solid radiopaque markers in 54 FD patients, and the patients were divided into two groups according to the results, one with delayed gastric emptying and the other with normal gastric emptying. Seventeen healthy volunteers acted as normal controls. Fasting and postprandial plasma levels and gastroduodenal mucosal levels of gastrointestinal hormones gastrin, somatostatin (SS) and neurotensin (NT)were measured by radioimmunoassay in all the subjects.G cells (gastrin-producing cells) and D cells (SS-producing cells) in gastric antral mucosa were immunostained with rabbit anti-gastrin polyclonal antibody and rabbit anti-SS polyclonal antibody, respectively, and analyzed quantitatively by computerized image analysis.RESULTS: The postprandial plasma gastrin levels, the fasting and postprandial plasma levels and the gastric and duodenal mucosal levels of NT were significantly higher in the FD patients with delayed gastric emptying than in those with normal gastric emptying and normal controls. The number and gray value of G and D cells and the G cell/D cell number ratio did not differ significantly between normal controls and the FD patients with or without delayed gastric emptying.CONCLUSION: Our findings suggest that the abnormalities of gastrin and NT may play a role in the pathophysiology of gastric dysmotility in FD patients, and the abnormality of postprandial plasma gastrin levels in FD patients with delayed gastric emptying is not related to the changes both in the number and gray value of G cells and in the G cell/D cell number ratio in gastric antral mucosa.

Ent-11α-Hydroxy-15-oxo-kaur-16-en-19-oic-acid Inhibits Growth of Human Lung Cancer A549 Cells by Arresting Cell Cycle and Triggering Apoptosis

Objective： To examine the apoptotic effect of ent-llα-hydroxy-15-oxo-kaur-16-en-19-oic-acid （5F）, a compound isolated from Pteris semipinnata L （PsL）, in human lung cancer A549 cells. Methods： A549 cells were treated with 5F （0-80 lag/ml） for different time periods. Cytotoxicity was examined using a Ml-I- method. Cell cycle was examined using propidium iodide staining. Apoptosis was examined using Hoechst 33258 staining, enzyme-linked immunosorbent assay （ELISA） and caspase-3 activity analysis. Expression of representative apoptosis-related proteins was evaluated by Western blot analysis. Reactive oxygen species （ROS） level was measured using standard protocols. Potential interaction of 5F with cisplatin was also examined. Results： 5F inhibited the proliferation of A549 cells in a concentration- and time-dependent manner. 5F increased the accumulation of cells in sub-G1 phase and arrested the cells in the G2 phase. Exposure to 5F induced morphological changes and DNA fragmentation that are characteristic of apoptosis. The expression of p21 was increased. 5F exposure also increased Bax expression, release of cytochrome c and apoptosis inducing factor （AIF）, and activation of caspase-3. 5F significantly sensitized the cells to cisplatin toxicity. Interestingly, treatment with 5F did not increase ROS, but reduced ROS production induced by cisplatin. Conclusion： 5F could inhibit the proliferation of A549 cells by arresting the cells in G2 phase and by inducing mitochondrial-mediated apoptosis.

Arsenic Trioxide Inhibits Proliferation in K562 Cells by Changing Cell Cycle and Survivin Expression

To study the mechanisms involved in the inhibition of chronic myeloid leukemic cells (K562) proliferation induced by arsenic trioxide (As 2O 3) and to explore the potential role of Survivin, an inhibitor of apoptosis protein, in the regulation of As 2O 3 induced cell apoptosis, K562 cells were cultured with As 2O 3 of different concentrations. Cells were collected for proliferation analysis by MTT assay. Cell cycle distribution and cell apoptosis were analyzed by flow cytometry. Expression of Survivin protein and mRNA were detected by flow cytometry and RT-PCR, respectively. Our results showed that As 2O 3 (2-10 μmol/L) inhibited K562 cells growth effectively, but it did not induce cells apoptosis significantly. The percentage of K562 cells at G 2/M phase increased in proportion to As 2O 3 concentrations, and the expression of Survivin mRNA and content of Survivin protein was up-regulated accordingly. It is concluded that As 2O 3 inhibited K562 cells growth by inducing cell cycle arrest mainly at G 2/M phase. Over-expression of Survivin gene and protein might be one of the possible mechanisms contributing to K562 cells' resistance to As 2O 3-induced apoptosis.

Expression of CTB-human Insulin(BA) Fusion Protein in Gynostemma Pentapyhllum Makino Callus Cells and Its Hypoglycemic Effect in Mice

The plant expression vector of choleratoxin B subunit（CTB）-human insulin（BA） fusion protein pBI121/（CTB-BA） was constructed first and then the Gynostemma Pentapyhllum Makino callus cell line that could express CTB-human insulin fusion protein was constructed and its hypoglycemic effect was evaluated in mice. The plant expression vector pBl 121/（CTB-BA） was digested with both BamI and SacI. Agrobacterium tumerfaciens strain LBA4404 was transformed with previously constructed recombinant plasmid pBI121/（CTB-BA） via the freeze thawing method, then CTB-BA gene was integrated to G Pentapyhllum Makino callus cells by co-culturing the cells with the transformed LBA4404 strain. The transformed G Pentapyhllum Makino callus cells were identified by DNA sequence assey and RT-PCR. The expressed product was identified by western-blot and its amount was tested by ELISA kit and its blood sugar decreasing effect was tested in mice. The sequences of synthetic CTB and human insulin genes（BA） were completely identical to those designed. Restriction map proved that the length of gene fragment in- serted into expression vector pBI121 was consistent with that expected. The sequence of genomic DNA of expressed product was completely identical to that designed. The result of RT-PCR was consistent with that expected. The expressed product showed a specific band with a relative molecular mass of 17000 by Western-blot. The human insulin expression amount was 6.03 μIU/mL according to the ELISA result. The animal test showed that only the G Pentapyhllum Makino callus cell line itself showed activity in decreasing the blood sugar of mice, however, the activity of the transformed G Pentapyhllum Makino callus cells was much higher, The plant expression vector pBI121/（CTB-BA） was constructed and expressed in the G Pentapyhllum Makino callus cells successfully for the first time. The trans- formed G Pentapyhllum Makino callus cells showed high activity in decreasing the blood sugar of mice. This study developed a new way for the development of oral administration insulin.

Genistein-induced Anticancer Effects on Acute Leukemia Cells Involve the Regulation of Wnt Signaling Pathway Through H4K20mel Rather Than DNA Demethylation

Objective:To investigate the effects and mechanisms of genistein on the gene expression in the Wnt pathway in acute leukemia(AL)cells.Methods:The expression of Wnt pathway genes and cell cycle-related genes were analyzed in two AL cell lines.Pyrophosphate sequencing was performed to determine the methylation degree.Then,the enrichment of H4K20mel and H3K9ac was determined using ChIP-qPCR.Flow cytometry was used to analyze the cell cycle.Results:The IC_(50) of genistein in the two AL cell lines was lower than that for the bone marrow mesenchymal stem cell line.Genistein upregulated H4K20mel,KMT5A and Wnt suppressor genes,including Wnt5a,and downregulated the downstream target genes of Wnt,such as c-myc and β-catenin.The methylation degree and H3K9ac enrichment in the Wnt5a promoter region remained unchanged.However,the enrichment of H4K20mel in the Wnt5a promoter and coding regions increased.In addition,genistein upregulated Phospho-cdc2,Mytl,Cyclin A,Cyclin E2,p21 and Phospho-histone H3,but downregulated Phospho-weel.Cell cycle arrest was induced in the G2/M phase.Conclusion:Genistein inhibits the activation of the Wnt pathway by promoting the expression of Wnt5a through the activation of KMT5A and enrichment of H4K20mel in the Wnt5a gene promoter and coding regions,rather than demethylation.Genistein also blocks the cell cycle in the G2/M phase.Therefore,genistein is a potential anti-leukemia drug.

Epigenetic Enabled Normal Human Cells, Lead to <i>First Cell</i>’s Unique Division System, Driving Tumorigenesis Evolution

Normal cells must become cancer-enabling before anything else occurs, according to latest literature. The goal in this mini-review is to demonstrate special tetraploidy in the enabling process. This we have shown from genomic damage, DDR (DNA Damage Response) activity with skip of mitosis leading to diploid G2 cells at the G1 border in need of chromatin repair for continued cell cycling to the special tetraploid division system. In several studies specific methylation transferase genes were activated in normal human cells in tissue fields, containing different cell growth stages of the cancerous process. Histology studies, in addition to molecular chemistry for identification of oncogenic mutational change, were a welcome change (see below). In a study on melanoma origin, DDR also showed arrested diploid cells regaining cycling from methylation transferase activity with causation of 2n melanocytes transforming to 4n melanoblasts, giving rise to epigenetic tumorigenesis enabled First Cells. Such First Cells were from Barrett’s esophagus shown to have inherited the unique division system from 4n diplochromosomal cells, first described in mouse ascites cancer cells (below). We discovered that the large nucleus prior to chromosomal division turned 90° relative to the cytoskeleton axis, and divided genome reductive to diploid, First Cells, in a perpendicular orientation to the surrounding normal cells they had originated from. This unique division system was herein shown to occur at metastasis stage, implying activity throughout the cancerous evolution. Another study showed 4-chromatid tetraploidy in development to B-cell lymphoma, and that such cancer cells also proliferated with participation of this unusual division system. Such participation has long been known from Bloom’s inherited syndrome with repair chiasmas between the four chromatids, also an in vitro observation by us. Our cytogenetic approach also revealed that they believed mitotic division in cancer cells is wrong because such cell divisions were found to be from an adaptation between amitosis and mitosis, called amitotic-mitosis. Amitosis means division without centrosomes, which has long been known from oral cancer cells, in that MOTCs (microtubule organizing center) were lacking centrioles. This observation calls for re-introduction of karyotype and cell division studies in cancer cell proliferation. It has high probability of contributing novel approaches to cancer control from screening of drugs against the amitotic-mitotic division apparatus.

Induction of APOBEC3G in human hepatoma cells by interferon-α stimulation

To clarify the role of APOBEC3G （A3G） in cellular defense against hepatitis B virus （HBV）, the expression of A3G in normal human liver and the regulation of the A3G expression in hepatoma cell line （HuH-7） were investigated. Expression level of APOBEC3s mRNA in human liver was determined by RT-PCR. HuH-7 and HepG2 cells were treated with various concentrations of IFN-α（0 U/ml, 100 U/ml, 500 U/ml, 1000 U/ml）for 12 h. The mRNA levels were measured by a quantitative RT-PCR, the results were normalized relative to the specimens without IFN-α stimulation. Total protein of HuH-7 cells treated with various concentrations of IFN-α for 48 h was subjected to Western blot analysis. For reporter gene assay, HuH-7 cells were transfected with the reporter plasmids containing IRF- E sites and its mutants with different lengths. Then the cells were treated with or without 1200 U/ml IFN-α for additional 12 h （ 1000 U/ml） after 24 h of transfection, and the cell lysate was prepared and assayed for lueiferase activity. It was found that normal human liver expressed the rnR_NA of A3G. A3G mRNA expression in HuH-7 and HepG2 cells were up-regulated by IFN-α stimulation in a dose-depen- dent manner. Western blot analysis indicated that A3G protein expression was also enhanced by IFN-α stimulation. Sequence analysis showed the existence of putative sites of IFN regulatory factor element （IRF-E） in 5＇ region of A3G gene upstream the initiation eodon. IFN-α stimulation results in 6- to 8- fold increase in lueiferase activity in cells transfeeted with the plasmid containing IRF-E sites of the 5＇ upstream sequences, whereas luciferase activity did not change in cells transfected with the plasmid containing mutant IRF-E sites or without IRF-E sites. As a conclusion, A3G are expressed in normal human liver. A3G expression was up-regulated by IFN-α stimulation in hepatoma cells and could be involved in host defense mechanisms against HBV. IRF-E site in 5＇ region of APOBEC3G gene upstream the initiation codon plays an important role in this process.

Glucose-6-Phosphate Dehydrogenase Deficiency: Difficulties in Diagnosis at the Souro Sanou University Hospital, Burkina Faso

Glucose-6-phosphate dehydrogenase deficiency is the most common enzymopathy worldwide. The precise prevalence of G6PD is unknown in Burkina Faso. The objective of the study was to describe the difficulties to diagnose this disease at the Souro Sanou University hospital (CHUSS) in Bobo-Dioulasso. It involved five patients comprising one child with homozygous SS sickle cell disease, one adolescent screened following a family investigation, and three adults including a man and two women. Blood smear stained with May Grunwald Giemsa was performed to look for specific signs of G6PD-deficient red blood cell and brilliant cresyl Blue for Heinz Bodies. A microscope Olympus BX53 equipped with a Camera (XC10) and connected to a computer was used to read blood smears and capture images. Genes sequencing by Sanger method were performed in a specialized laboratory in molecular genetics. For each analysis, the protocol and instructions of the equipment and reagent manufacturer were applied. Of the five patients, three had anemia and only one had hyperreticulocytosis. Two patients had biological signs of hemolysis and one patient had an elevated CRP. Blood smear stained with MGG and cresyl blue showed specific signs of G6PD-deficient red blood cells and Heinz bodies in all patients. Biochemical analysis and molecular typing confirmed G6PD deficiency. The presence of G6PD-deficient red blood cells in the blood smear guides the diagnosis of G6PD deficiency. The diagnosis is biochemical and is based on the combined measurement of G6PD plus pyruvate kinase and/or hexokinase.

STUDY ON THE THERAPEUTIC EFFECT OF ACUPUNCTURE THERAPY FOR TREATMENT OF EPIGASTRALGIA

In the present paper, the therapeutic effect of acupuncture in treatment of 42 cases of epigastralgia was observed using multiple objective indexes, including electrogastrogram (EGG), output of gastric acid and pepsase, plasma prostaglandin (PG) E and gastrin contents, the number and morphological structure of gastrin (G) cells of the antrum mucosa. These 42 cases included 18 cases of deficiency syndrome type, 13 excess syndrome type and 11 mixed type of deficiency and excess. Zhongwan (CV 12), Neiguan (PC 6) and Zusanli (ST 36) were punctured combined with other acupoints according to syndrome patterns. After treatment, 32 cases (76.19%) were cured, 6(14.29%) had remarkable improvement and 4 (9.52%) had improvement, with a cure plus markedly effective rate of 90.48%. Gastroscopic and EGG examination suggested that the function and structure of the stomach returned to normal after acupuncture. In addition, acupuncture stimulation had a bi directional regulative action on gastric acid secretion, gastrin content, EGG activity, etc. Conclusion: Acupuncture treatment has a good regulative action on gastric function and structure in epigastralgia patients.

Intrinsic apoptotic pathway and G2/M cell cycle arrest involved in tubeimoside I-induced EC109 cell death

Objective： Squamous esophageal carcinoma is highly prevalent in developing countries, especially in China. Tu Bei Mu （TBM）, a traditional folk medicine, has been used to treat esophageal squamous cell carcinoma （ESCC） for a long term. tubeimoside I （TBMS1） is the main component of TBM, exhibiting great anticancer potential. In this study, we investigated the mechanism of TBMS1 cytotoxic effect on EC109 cells. Methods： Comparative nuclear proteomic approach was applied in the current study and we identified several altered protein spots. Further biochemical studies were carried out to detect the mitochondrial membrane potential, cell cycle and corresponding proteins＇ expression and location. Results： Subcellular proteomic study in the nucleus from EC109 cells revealed that altered proteins were associated with mitochondrial function and cell proliferation. Further biochemical studies showed that TBMSl-induced molecular events were related to mitochondria-induced intrinsic apoptosis and P21-cyclin B 1/cdc2 complex-related G2/M cell cycle arrest. Conclusions： Considering the conventional application of TBM in esophageal cancer, TBMS1 therefore may have a great potential as a chemotherapeutic drug candidate for ESCC.

Bio-compatibility and cytotoxicity studies of water-soluble CuInS_2-ZnS-AFP fluorescence probe in liver cancer cells

BACKGROUND： The oncogenesis of hepatocellular carcinoma（HCC） is not clear. The current methods of the pertinent studies are not precise and sensitive. The present study was to use liver cancer cell line to explore the bio-compatibility and cytotoxicity of ternary quantum dots（QDs） probe and to evaluate the possible application of QDs in HCC.METHODS： CuInS_2-ZnS-AFP fluorescence probe was designed and synthesized to label the liver cancer cell HepG 2. The cytotoxicity of CuInS_2-ZnS-AFP probe was evaluated by MTT experiments and flow cytometry. RESULTS： The labeling experiments indicated that CuInS_2-ZnS QDs conjugated with AFP antibody could enter HepG 2 cells effectively and emit intensive yellow fluorescence by ultraviolet excitation without changing cellular morphology. Toxicity tests suggested that the cytotoxicity of CuInS_2-ZnS-AFP probe was significantly lower than that of CdT e-ZnS-AFP probe（t test, F=0.8, T=-69.326, P〈0.001）. For CuInS_2-ZnS-AFP probe, timeeffect relationship was presented in intermediate concentration（〉20%） groups（P〈0.05） and dose-effect relationship was presented in almost all of the groups（P〈0.05）. CONCLUSION： CuInS_2-ZnS-AFP QDs probe had better biocompatibility and lower cytotoxicity compared with CdT e-ZnS-AFP probe, and could be used for imaging the living cells in vitro.

Research and simulation on synchronization algorithm of PSS in a 5G system based on block cross-correlation

In response to the downlink synchronization requirements of the user equipment(UE)or third-party radio equipment in fifth-generation(5G)mobile communication systems,a synchronization algorithm of primary synchroni-zation signal(PSS)was designed and developed in the 5G system based on block cross-correlation.According to the new characteristics of the 5G synchronization channel and broadcast channel,starting from the traditional downlink synchronization algorithm of long-term evolution(LTE),the detection performance of the algorithm under a low signal-to-noise ratio(SNR)is improved by introducing an incoherent accumulation,and the new scheme of joint coarse frequency offset estimation is used to improve the frequency offset estimation performance.Finally,the performance of the proposed synchronization algorithm is verified by conducting a simulation on a 5G downlink simulation platform based on MATLAB software.Simulation results show that the improved downlink synchronization algorithm has stable performance in the tapped delay line-C(TDL-C)and additive white Gaussian noise(AWGN)channels with large frequency deviation and low SNR.

Viral infections and cell cycle G2/M regulation

Progression of cells from G2 phase of the cell cycle to mitosis is a tightly regulated cellular process that requires activation of the Cdc2 kinase, which determines onset of mitosis in all eukaryotic cells. In both human and fission yeast (Schizosaccharomyces pombe) cells, the activity of Cdc2 is regulated in part by the phosphorylation status of tyrosine 15 (Tyr15) on Cdc2, which is phosphorylated by Wee1 kinase during late G2 and is rapidly dephosphorylated by the Cdc25 tyrosine phosphatase to trigger entry into mitosis. These Cdc2 regulators are the downstream targets of two well- characterized G2/M checkpoint pathways which prevent cells from entering mitosis when cellular DNA is damaged or when DNA replication is inhibited. Increasing evidence suggests that Cdc2 is also commonly targeted by viral proteins, which modulate host cell cycle machinery to benefit viral survival or replication. In this review, we describe the effect of viral protein R (Vpr) encoded by human immunodeficiency virus type 1 (HIV-1) on cell cycle G2/M regulation. Based on our current knowledge about this viral effect, we hypothesize that Vpr induces cell cycle G2 arrest through a mechanism that is to some extent different from the classic G2/M checkpoints. One the unique features distinguishing Vpr-induced G2 arrest from the classic checkpoints is the role of phosphatase 2A (PP2A) in Vpr-induced G2 arrest. Interestingly, PP2A is targeted by a number of other viral proteins including SV40 small T antigen, polyomavirus T antigen, HTLV Tax and adenovirus E4orf4. Thus an in-depth understanding of the molecular mechanisms underlying Vpr-induced G2 arrest will provide additional insights into the basic biology of cell cycle G2/M regulation and into the biological significance of this effect during host-pathogen interactions.

Effect of Mica Monomer Powder on Chief and Parietal Cells as well as G and D Cells in Gastric Mucosa of Chronic Atrophic Gastritis in Rats

Objective： To study the regulative action of mica monomer powder preparation on the chief and parietal cells as well as G and D cells in the gastric mucosa of the experimental atrophic gastritis （CAG） rats. Methods： Intervention therapy was given to the experimental CAG rats at three different doses of mica monomer powder preparation to evaluate the changes of chief and parietal cells as well as G and D cells in the gastric mucosa and the histopathological changes of gastric mucosa. Results： Mica monomer powder preparation at three different doses could increase the amount of chief and parietal cells as well as G and D cells in gastric mucosa of the experimental CAG rats and alleviate and control the inflammation of gastric mucosa and the atrophy of gastric mucosa glands. Especially, better effects were shown in the mid and high dose groups. Conclusion： Mica has the pharmacological action of protecting the gastric mucosa, promoting the regeneration of gastric glands, enhancing blood flow of the gastric mucosa, and consequently improving the inflammatory responses of the gastric mucosa. One of the mechanisms is associated with promoting the secretion of gastric acid and gastric pepsin and regulating the neuroendocrine mechanism including gut hormone secretion （gastrin and somatostatin） by increasing the number of chief and parietal cells as well as G and D cells.

Cucurbitacin B-induced G2/M cell cycle arrest of conjunctival melanoma cells mediated by GRP78-FOXM1-KIF20A pathway

Conjunctival melanoma(CM) is a rare and fatal malignant eye tumor. In this study, we deciphered a novel anti-CM mechanism of a natural tetracyclic compound named as cucurbitacin B(CuB). We found that CuB remarkably inhibited the proliferation of CM cells including CM-AS16,CRMM1, CRMM2 and CM2005.1, without toxicity to normal cells. CuB can also induce CM cells G2/M cell cycle arrest. RNA-seq screening identified KIF20A, a key downstream effector of FOXM1 pathway, was abolished by CuB treatment. Further target identification by activity-based protein profiling chemoproteomic approach revealed that GRP78 is a potential target of CuB. Several lines of evidence demonstrated that CuB interacted with GRP78 and bound with a Kdvalue of0.11 μmol/L. Furthermore, ATPase activity evaluation showed that CuB suppressed GRP78 both in human recombinant GRP78 protein and cellular lysates. Knockdown of the GRP78 gene significantly induced the downregulation of FOXM1 and related pathway proteins including KIF20A, underlying an interesting therapeutic perspective. Finally, CuB significantly inhibited tumor progression in NCG mice without causing obvious side effects in vivo. Taken together, our current work proved that GRP78-FOXM1-KIF20A as a promising pathway for CM therapy, and the traditional medicine CuB as a candidate drug to hinder this pathway.

Role of reactive oxygen species in the antiproliferative effects of metavanadate on human prostate cancer DU145 cells

In the present study, the effects of metavanadate on the human prostate cancer cell line DU145 and the underlying mechanism were investigated. The results showed that metavanadate can cause cell cycle arrest at G2/M phase which was evidenced by cell cycle analysis and the increased phosphorylation of Cdc2 at its inactive Tyr-15 site. In addition, the results showed that metavanadate can induce reactive oxygen species （ROS） elevation and decrease the level of Cdc25C. This process can be rescued by an antioxidant, N-acetyl cysteine. In conclusion, the results demonstrate that metavanadate can inhibit cell proliferation via cell cycle arrest at G2/M phase in DU145 ceils. Metavanadate-induced ROS formation may play an important role in this process by mediating the degradation of Cdc25C.

Substituent-regulated highly X-ray sensitive Os(Ⅵ)nitrido complex for low-toxicity radiotherapy

A high efficiency and low toxicity radiosensitizer,OsN(PhenOH)Cl_3,was designed and synthesized through substituent regulation.To the best of our knowledge,this is the first osmium-based coordination complex radiosensitizer.The experimental results shown that this radiosensitizer induced G2/M cell cycle arrest mainly through induction of intracellular ROS overproduction.

The Release Behavior,Biocompatibility and Physical Properties of Aid-loaded Strontium Doped Calcium Phosphate Cement

The effect of concurrent attendance of two inhibitors of bone degradation,namely Alendronate(Aid)sodium trihydrate and Strontium(Sr),on Calcium Phosphate Cement(CPC)characteristics was explored.To this aim,5 wt%Strontium and 21 mM Alendronate sodium trihydrate were used in calcium phosphate cement and setting time,ion and drug release were analyzed.RAW264.7 and G cell were cultured on cement samples and Tartrate-Resistant Acid Phosphatase(TRAP),Alkaline phosphatase(ALP)activity and MTT assay were studied.The results of structural analysis indicated that 21 mM Aid did not let the cement set.Therefore,colloidal silica was added to the cement formula and successfully decreased the setting time.In vitro tests showed Sr-loaded sample had a greater inhibitory effect on biocompatibility of G cells than Aid-loaded and Sr-Ald-loaded samples.In addition,the findings about osteoblast MTT and ALP activity indicated that Sr was more effective in osteogenic activity of G cells.The simultaneous presence of Aid and Sr in Calcium Phosphate Cement(CPC)was not as effective in its biocompatibility as the presence of Sr alone.