OBJECTIVETo investigate the role of endogenous hydrogen sulfide (H2S) in erectile dysfunction (ED) induced by androgen deficiency.

METHODSWe randomly divided 30 eight-week-old healthy male SD rats into six groups: 2-week control (A), 4-week control (B), 2-week castration (C), 4-week castration (D), 2-week castration + androgen replacement (E), and 4-week castration + androgen replacement (F), those in groups E and F subcutaneously injected with testosterone propionate (TP) at the physiological dose of 3 mg/kg per day after castration, while those in the other groups with isodose oil instead. At 2 and 4 weeks after operation, we determined the level of serum testosterone (T) , intracavernous pressure (ICP) , mean carotid arterial pressure (MAP) of the rats, measured the concentration of H2S in the plasma and corpus cavernosum tissue, and detected the expressions of cystathionine-P3-synthase (CBS) and cystathionine-gamma-lyase (CSE) by immunohistochemistry and Western blot.

RESULTSThe serum T level was significantly lower in group C ([0.63 +/- 0.15] nmol/L) than in A ( [ 16.55 +/- 4.17] nmol/L) and E ( [ 18.99 +/- 4.62] nmol/L) (P <0.05), as well as in group D ([0.70 +/-0.22] nmol/L) than in B ([15.44 +/-5.18] nmol/L) and F ([20.99 +/-6.41] nmol/L) (P <0. 05) , and so were ICP/MAP after 5 and 7 V electrical stimulation of the pelvic ganglia (P <0. 05) , H2 S concentration (P <0.05), and the expressions of CBS and CSE (P <0.05). The expressions of CBS and CSE proteins were also significantly decreased in group C as compared with D (P <0.05).

CONCLUSIONThe reduced expressions of CBS and CSE may inhibit the H2 S signaling pathway, which might be one of the mechanisms underlying androgen deficiency-induced ED in rats.

Androgens ; deficiency ; Animals ; Cystathionine beta-Synthase ; metabolism ; Cystathionine gamma-Lyase ; metabolism ; Erectile Dysfunction ; metabolism ; Hydrogen Sulfide ; metabolism ; Male ; Orchiectomy ; Penis ; metabolism ; Rats ; Rats, Sprague-Dawley

Platinum-based anticancer drugs have been becoming one of the most effective drugs for clinical treatment of malignant tumors for its unique mechanism of action and broad range of anticancer spectrum. But, there are still several problems such as side effects, drug resistance/cross resistance and no-specific targeting, becoming obstacles to restrict its expanding of clinical application. In recent years, supramolecular chemistry drug delivery systems have been gradually concerned for their favorable safety and low toxicity. Supramolecular macrocycles-platinum complexes increased the water solubility, stability and safety of traditional platinum drugs, and have become hot focus of developing novel platinum-based anticancer drugs because of its potential targeting of tumor tissues/organs. This article concentrates in the research progress of the new drug delivery system between platinum-based anticancer drugs with three generations of macrocycles: crown ether, cyclodextrin, cucurbituril and calixarene.
Antineoplastic Agents ; pharmacology ; Calixarenes ; Crown Compounds ; Cyclodextrins ; Drug Delivery Systems ; Humans ; Macrocyclic Compounds ; pharmacology ; Neoplasms ; drug therapy ; Platinum Compounds ; pharmacology

OBJECTIVETo investigate the expression of guanylin in colorectal cancer.

METHODSThe expression of guanylin was examined by RT-PCR and semiquantitative analysis in 20 cases of colorectal cancer, and its relationship with clinical characteristics was analyzed.

RESULTSThe positive expression of guanylin in normal tissue (80%, 16/20) was significantly higher than that in tumor tissue (35%, 7/20) (P<0.01). The same result was found in the semiquantitative analysis of 14 cases with differential expression. Differential expression of guanylin in colorectal cancer was associate with TNM stage (P<0.05), not with sex, Borrmann type and degree of differentiation (all P>0.05).

CONCLUSIONThere is differential expression of guanylin in colorectal cancer, and this kind of differential expression is associated with tumor TNM stage.

Colorectal Neoplasms ; metabolism ; pathology ; Female ; Gastrointestinal Hormones ; metabolism ; Humans ; Male ; Middle Aged ; Natriuretic Peptides ; metabolism ; Neoplasm Staging

OBJECT: To obtain values of normal human lung and diffuse pathological changes, in order to provide a simple and convenient diagnostic method for measuring human visceral organs in the autopsy of pathology and forensic pathology. METHODS: The exact mass, volume and density of normal and pathological lung were synchronously measured with the intelligentized volume-densimeter made by authors. RESULTS: The date-base about the volume and density of human lung with different races were established for anatomy, anthropology and biodynamics. In two cases of over-load in circulation and water toxicosis, the severe lung edema was proved with the scale of lung density, which was atypical edema in the lung tissue. CONCLUSION Measurement of visceral organs in the autopsy can assist to an integrative pathological diagnosis.
Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Anthropometry/methods* ; Autopsy ; Child ; Child, Preschool ; Female ; Forensic Medicine ; Humans ; Infant ; Infant, Newborn ; Lung/pathology* ; Male ; Middle Aged ; Organ Size ; Pulmonary Edema/pathology* ; Sex Factors ; Young Adult

OBJECTIVETo establish rhesus haploidentical hematopoietic stem cell transplantation model by nonmyeloablative conditioning, and examine the effects of mesenchymal stem cells (MSC) in haploidentical transplantation.

METHODSThe recipient haploidentical rhesus monkeys were conditioned with a nonmyeloablative regimen consisted of fludarabine, cyclophosphamide, 200 cGy total body irradiation, and rabbit anti-human thymocyte globulin. Cyclosporine A, mycophenolate mofetil and anti CD25 antibody were used for graft versus host disease (GVHD) prophylaxis. Rhesus monkeys in one group were given hematopoietic stem cell (HSC) only, while in the other group HSC combined with MSC. The differences in hematopoiesis recovery, chimerism level, and GVHD between the two groups were evaluated.

RESULTSStable chimerism could be achieved in recipient monkeys. Hematopoiesis recovery was mainly related with chimerism level. MSC seemed capable of facilitating HSC engraftment, as there were more mixed chimerism and less GVHD occurrence in the HSC combined with MSC recipient group.

CONCLUSIONA rhesus haploidentical hematopoietic stem cell transplantation model is successfully established by nonmyeloablative conditioning. MSC was of great benefit to haploidentical transplantation.

Animals ; Chimerism ; Graft vs Host Disease ; prevention & control ; Haploidy ; Hematopoietic Stem Cell Transplantation ; Macaca mulatta ; genetics ; surgery ; Mesenchymal Stem Cell Transplantation ; Models, Animal ; Transplantation Conditioning

Traditional microtubule inhibitors fail to significantly enhance the effect of colorectal cancer;hence,new and efficient strategies are necessary.In this study,a supramolecular nanoreactor(DOC@TA-Fe3+)based on tannic acid(TA),iron ion(Fe3+),and docetaxel(DOC)with microtubule inhibition,reactive oxygen species(ROS)generation,and glutathione peroxidase 4(GPX4)inhibition,is prepared for ferroptosis/apoptosis treatment.After internalization by CT26 cells,the DOC@TA-Fe3+nanoreactor escapes from the lysosomes to release payloads.The subsequent Fe3+/Fe2+conversion mediated by TA reducibility can trigger the Fenton reaction to enhance the ROS concentration.Additionally,Fe3+can consume gluta-thione to repress the activity of GPX4 to induce ferroptosis.Meanwhile,the released DOC controls microtubule dynamics to activate the apoptosis pathway.The superior in vivo antitumor efficacy of DOC@TA-Fe3+nanoreactor in terms of tumor growth inhibition and improved survival is verified in CT26 tumor-bearing mouse model.Therefore,the nanoreactor can act as an effective apoptosis and ferroptosis inducer for application in colorectal cancer therapy.

This study was aimed to analyze the mRNA expression of cytokines (TGF-beta, IL-2, IL-6, IL-10, IFN-gamma, TNF-alpha, FAS-L) in five rhesus treated with haploidentical peripheral blood stem cell transplantation after nonmyeloablative preparative regimens and to explore the role of these cytokines in the development and pathology of acute graft-versus-host-disease (aGVHD). Five rhesus monkeys received nonmyeloablative haploidentical peripheral blood stem cells transplantation. Semi-quantitative reversed transcription polymerase chain reaction (RT-PCR) was used to analyze the kinetics of cytokine mRNA expression in the transplantation and aGVHD. The results showed that five rhesus monkeys acquired hematopoietic reconstitution successfully. The graft was rejected in one monkey which survived without disease, the other four achieved mixed chimerism and full donor chimerism. Chimerism of low centigrade in one monkey achieved high centigrade at 35 days after donor stem cell infusion. Intestinal aGVHD grade III developed in one monkey. Cytokines of Th1 and Th2 changed after transplantation. In period of aGVHD, expression of TGF-beta decreased but all others increased in various levels. When donor chimerism decreased, the cytokines decreased accordingly. It is concluded that the decrease of TGF-beta mRNA may be an indicator to predict aGVHD, and can be used as a differential diagnostic indicator for intestinal GVHD.
Animals ; Cytokines ; biosynthesis ; genetics ; Graft vs Host Disease ; diagnosis ; metabolism ; Haploidy ; Macaca mulatta ; Peripheral Blood Stem Cell Transplantation ; adverse effects ; RNA, Messenger ; biosynthesis ; genetics ; Transforming Growth Factor beta ; biosynthesis ; genetics

OBJECTIVETo investigate the differentiation-related proteins in human gastric carcinoma cell lines by comparative proteomics.

METHODSThe holoproteins of human gastric carcinoma cell lines MKN28, SGC7901 and BGC823 were measured by two-dimensional gel electrophoresis and matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Some proteins identified by proteomics were tested by Western blot in the cell strains and tissues of gastric carcinoma.

RESULTS14 differential protein spots were found in the 3 gastric carcinoma cell lines, among them 8 spots were identified by MALDI-TOF-MS. These proteins were probably thioredoxin peroxidase, glyceraldehyde-3-phosphate dehydrogenase (GAPD), beta-tubulin polypeptide, hypothetical protein, zinc finger protein (ZNF) 139, protein-tyrosine kinase, calreticulin precursor, and tropomyosin, proteins related with biological behavior of gastric carcinoma cells such as signal transduction, cellular homeostasis, glycolysis, antioxidation action, multidrug resistance(MDR), etc. The expressions of those proteins in gastric cancer cells and tissues identified by Western blot were consistent with the results obtained by proteomics.

CONCLUSIONDifferential proteins are found in 3 human gastric carcinoma cell lines, mainly, proteins related with cell signaling, maintenance of homeostasis, glycolysis, metabolism of anti-cancer drug and anti-oxidative injury, etc.

Adenocarcinoma ; metabolism ; pathology ; Adult ; Aged ; Blotting, Western ; Cell Line, Tumor ; Electrophoresis, Gel, Two-Dimensional ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Glyceraldehyde-3-Phosphate Dehydrogenases ; metabolism ; Humans ; Male ; Middle Aged ; Protein-Tyrosine Kinases ; metabolism ; Proteome ; analysis ; Proteomics ; methods ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Stomach Neoplasms ; metabolism ; pathology

OBJECTIVETo investigate the biological properties of cultured human oral mucosa epithelium using autologous serum in order to provide a new material for tissue engineering urethra.

METHODSThe cultured oral mucosa epithelium was respectively transplanted beneath the skin, above the deep fascia and in the wound of the athymic mice. The specimens were taken at 2, 3, 4, and 6 weeks posttransplantation, and processed for (1) immunofluorescence anti-HLA staining to determine graft acceptance, and (2) anti-human IV collagen and antihuman laminin immunohistochemical staining procedures to indicate the basement membrane formation.

RESULTSAll the grafts survived and grew very well. The grafts were positive to anti-HLA. Collagen type IV and laminin were detected at the dermo-epidermal junction in all groups from day 14, and increasing in density up to day 21.

CONCLUSIONShe cultured human oral mucosa epithelium by autologous serum could develop an excellent functional epithelium tissue, which would be used to reconstruct urethra and repair wound.

Animals ; Cells, Cultured ; Epithelium ; transplantation ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Mouth Mucosa ; cytology ; Serum ; Skin Transplantation ; Tissue Culture Techniques ; Tissue Engineering ; methods ; Tissue Scaffolds ; Tissue Transplantation ; methods ; Transplantation, Heterologous

Monitoring engraftment of donor cells after allogeneic transplantation is the key of assessing successful establishment of animal transplantation model. The purpose of this study was to establish a method for analysis of chimerism in rhesus transplantation model. Y-specific sequence in rhesus was amplified by the polymerase chain reaction (PCR), method for analysis of chimerism in rhesus after sex-mismatched transplantation was established; the feasibility and sensitivity of the approach were tested by using serial DNA mixtures of sex-mismatched individuals; the accuracy of results was confirmed by chromosome karyotype analysis simultaneously; Chimerisms of one rhesus received allogeneic stem cell transplantation and the other received mesenchymal stem cells (MSC) transfusion were detected by this method. The results showed that a 176 bp long sequence of PCR product was gained in male rhesus, while no product was gained in female rhesus. The sensitivity of this method was up to 0.05% (male/female DNA ratio). Male donor chimerism were found on day 7 and 14 after allogeneic stem cell transplantation by Y-specific sequence and chromosome karyotype analysis. Otherwise, male donor chimerism was found in peripheral blood at 1 hour and in bone marrow on day 30 after MSC transfusion by this method, but no male donor chimerism was found after MSC transfusion using chromosome karyotype analysis. In conclusion, this rapid, sensitive approach can used to assess chimerism in experiments of rhesus alloorgan transplantation and cell transfusion.
Animals ; Base Sequence ; Female ; Macaca mulatta ; Male ; Mesenchymal Stem Cell Transplantation ; methods ; Models, Animal ; Molecular Sequence Data ; Transplantation Chimera ; blood ; genetics ; Transplantation, Homologous ; Y Chromosome ; genetics