Anemia, Aplastic ; therapy ; Child ; Female ; HLA Antigens ; genetics ; immunology ; Humans ; Mesenchymal Stem Cell Transplantation ; Peripheral Blood Stem Cell Transplantation

Syl948 is a synthesized selective S1P1 agonist with novel structure. HTRF-IP1 test indicated that Syl948-P, the active form of Syl948 in vitro, has strong activity against S1P1 (EC50: 83 +/- 16 nmol x L(-1)), but its effect on S1P3 was very weak (EC50: 1 026 +/- 90 nmol x L(-1)). In SD rats, oral administration of Syl948 10 mg x kg(-1) significantly decreased the peripheral blood lymphocytes (PBL), with the maximal PBL inhibition rate of 63%, which was as similar as equal dose of fingolimod (FTY720). Oral administration of Syl948 10 mg x kg(-1) had no effect on heart rate of SD rats, which was better than FTY720. Daily oral administration with Syl948 (2 or 4 mg x kg(-1)) significantly prolonged the survival time of the allografts of skin slice on mice. In summary, the above results demonstrated that Syl948 has great selectivity in vitro and good activity in vivo, which indicated its potential use as an anti-rejection drug in skin transplantation.
Animals ; Fingolimod Hydrochloride ; Graft Survival ; drug effects ; Immunosuppressive Agents ; pharmacology ; Lymphocytes ; drug effects ; Mice ; Propylene Glycols ; pharmacology ; Rats ; Receptors, Lysosphingolipid ; agonists ; Skin Transplantation ; Sphingosine ; analogs & derivatives ; pharmacology ; Transplantation, Homologous

OBJECTIVETo investigate the role of p38 MAPK on ischemic postconditioning (IPO) attenuating pneumocyte apoptosis after lung ischemia/reperfusion injury (LIRI).

METHODSForty adult male SD rats were randomly divided into 5 groups based upon the intervention (n = 8): control group (C), LIR group (I/R), LIR + IPO group (IPO), IPO + solution control group (D), IPO + SB203580 group (SB). Left lung tissue was isolated after the 2 hours of reperfusion, the ratio of wet lung weight to dry lung weight (W/D), and total lung water content (TLW) were measured. The histological structure of the left lung was observed under light and electron transmission microscopes, and scored by alveolar damage index of quantitative assessment (IQA). Apoptosis index (AI) of lung tissue was determined by terminal deoxynuleotidyl transferase mediated dUTP nick end and labeling (TUNEL) method. The mRNA expression and protein levels of and Bax were measured by RT-PCR and quantitative immunohistochemistry (IHC).

RESULTSCompared with C group, W/D, TLW, IQA, AI and the expression of Bax of I/R were significantly increased, the expression of Bcl-2 and Bcl-2/Bax were significantly decreased (P < 0.05, P < 0.01), and was obviously morphological abnormality in lung tissue. Compared with I/R group, all the indexes of IPO except for the expression of Bcl-2 and Bcl-2/ Bax were obviously reduced, the expression of Bcl-2 and Bcl-2/Bax were increased (P < 0.05, P < 0.01). All the indexes between D and IPO were little or not significant( P > 0.05). The expression of Bcl-2 and Bcl-2/Bax of SB were significantly increased and other indexes were reduced than those of IPO (P < 0.05, P < 0.01).

CONCLUSIONIPO may attenuate pneumocyte apoptosis in LIRI by inactivation of p38 MAPK, up-regulating expression of Bcl-2/Bax ratio.

Alveolar Epithelial Cells ; cytology ; Animals ; Apoptosis ; Disease Models, Animal ; Ischemic Postconditioning ; Lung ; blood supply ; enzymology ; pathology ; Male ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; enzymology ; pathology ; prevention & control ; bcl-2-Associated X Protein ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVETo investigate the role and significance of ATP-sensitive K+ channels in the pathological process of hypoxia hypercapnia-induced pulmonary vasoconstriction (HHPV) and the relationship with ERK1/2 signal pathway in rats.

METHODSWe made the third pulmonary artery rings of SD rats, used the model of pulmonary artery rings perfusion in vitro. Under acute hypoxia hypercapnia condition, and observed the effects of the three stages of HHPV incubated by glybenclamide(Gly) and the combined application of Gly and U0126. At the same time, the values of rings' tension changes were recorded via the method of hypoxia hypercapnia conditions reactivity.

RESULTSUnder the normoxia condition, the values of the third pulmonary artery rings tension were relatively stable, but under the hypoxia hypercapnia condition, we observed a biphasic pulmonary artery contractile response compared with N group (P < 0.05, P < 0.01). When the third pulmonary artery rings incubated by Gly, it's phase II persistent vasoconstriction was enhanced compared with the H group (P < 0.05, P < 0.01), and the phase I vasoconstriction was also heightened. Moreover, under the hypoxia hypercapnia condition, U0126 could significantly relieve the phase II persistent vasoconstriction compared with HD group (P < 0.05, P < 0.01) induced by Gly, but the phase I acute vasoconstriction and the phase I vasodilation had no changes (P > 0.05).

CONCLUSIONGly may mediate HHPV via activating ERK1/2 signal transduction pathway.

Animals ; Glyburide ; pharmacology ; Hypercapnia ; metabolism ; physiopathology ; Hypoxia ; metabolism ; physiopathology ; In Vitro Techniques ; MAP Kinase Signaling System ; physiology ; Male ; Pulmonary Artery ; drug effects ; metabolism ; physiology ; Rats ; Rats, Sprague-Dawley ; Vasoconstriction ; drug effects

OBJECTIVETo explore the influence of the DNA repair gene ERCC2 single nucleotide polymorphisms (SNPs) rs13181, rs1618536, and rs1799793 on male idiopathic infertility in Ningxia, China.

METHODSUsing MassArray, we conducted a case-control study and genotyped three ERCC2 SNPs rs13181, rs1618536, and rs1799793 for 351 males (aged 31.0 +/- 4.2 years) with idiopathic infertility and another 327 normal fertile men (aged 33.0 +/- 5.9 years) as controls.

RESULTSThe ERCC2 AnyG-anyA-anyA genotypes were significantly associated with an increased risk of idiopathic infertility (OR 0.414, 95% CI 0.176 - 0.970), while the three single ERCC2 SNPs rs13181, rs1618536, and rs1799793 showed no significant differences between the cases and controls (P > 0.05).

CONCLUSIONThe ERCC2 SNPs rs13181, rs1618536, and rs1799793 play a role of interaction in male idiopathic infertility in Ningxia, contributing to the risk of the disease.

Adult ; Case-Control Studies ; China ; DNA Repair ; Genotype ; Humans ; Infertility, Male ; genetics ; Male ; Polymorphism, Single Nucleotide ; Xeroderma Pigmentosum Group D Protein ; genetics

OBJECTIVETo study the indication and character of the lateral-cervical approach for treating dumble-shape neurogenic tumors in cervical spine.

METHODSRetrospectively review the clinical data of 14 dumble-shape neurogenic tumors in cervical spine, from October 2005 to October 2011. Among them 8 were males and 6 were females, range from 11 to 60 years old. The maximum tumor diameter range from 3.0 to 8.0 cm, with an average of 4.8 cm; the intraspinal tumor diameter range from 1.3 to 3.8 cm, with an average of 2.1 cm. According to Asazuma classification, 9 cases were type IIc, 2 cases were type IIIb, 2 cases were type IV, 1 case was type VI. Involving the neck segment C(1)-C(2) in 1 case, C(2)-C(3) in 1 case, C(3)-C(4) in 2 cases, C(4)-C(5) in 2 cases, C(5)-C(6) in 3 cases, C(6)-C(7) in 4 cases and C(2)-C(4) in 1 case. All cases performed surgery with general anethesia. The head and neck surgeon performed surgery with lateral cervical approach, in the space between the anterior and the medius scalenus, exposed the transverse process and the intervertebral foramen as the anatomy marker, resected the extraspinal tumor part. The neurosurgery expanded the intervertebral foramen, and resected the intraspinal tumor with microscope, and repaired the dura. Then head and neck surgeon closed the wounds.

RESULTSPathology proved 3 neurolimmoas and 11 Schwannomas, 12 cases received gross total resection, 2 cases received subtotal resection, the average blood loss during operation was 292 ml, the average operation time was 129 minutes, the average stay in hospital days was 7.1 days. The vertebral artery were exposed in 2 cases, and no vertebral artery injury occurred, there were 3 cases dissect the cervical nerve roots. No cerebrospinal fluid leakage, hematoma, newly branchial plexus injury, sympathic nerve injury or tracheal edema occurred. In 3 to 24 months, with an average of 13.5 months follow-up period, 2 cases with subtotal resection had no tumor progression, and 12 cases with gross total resection had no tumor recurrence.

CONCLUSIONSLateral-cervical approach is minimal invasive, easily to perform and recovery fine. It can be adopt for Asazuma type IIc, IIIb and IV tumors which not grow over the midline in spine and expand to deep layer of the deep cervical fascia out spine.

Adolescent ; Adult ; Cervical Vertebrae ; surgery ; Child ; Female ; Humans ; Male ; Middle Aged ; Neurilemmoma ; surgery ; Neurofibroma ; surgery ; Neurosurgical Procedures ; methods ; Retrospective Studies ; Spinal Neoplasms ; surgery ; Young Adult

The purpose of this study was to explore the roles of cytokines IL-2, TNF-alpha, IL-10 and IL-8 in the pathogenesis of acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. The incidence of aGVHD was observed in 33 patients undergoing allogeneic hematopoietic stem cell transplantation. The aGVHD was clinically diagnosed. Sera from the 33 patients were taken before and after allogeneic hematopoietic stem cell transplantation. The IL-2, TNF-alpha, IL-8, IL-10 levels in serum of 33 patients were measured serially by using radioimmuno-assay (RIA). aGVHD occurred in 13 patients including 8 patients with aGVHD I and 5 patients with aGVHD II-IV. The results showed that the circulating levels of IL-2 and TNF-alpha were markedly elevated during aGVHD and strongly correlated with the severity of aGVHD as compared with patients without aGVHD. However, the level of the IL-10 in patients with aGVHD was significantly lower than that in patients without aGVHD. The change of IL-8 level was not significant statistically. It is concluded that IL-2 and TNF-alpha may play important roles in the pathogenesis of aGVHD, and measurement of serum IL-2 and TNF-alpha levels after allo-HSCT can provide predictive indicator for acute GVHD.
Adolescent ; Adult ; Female ; Graft vs Host Disease ; blood ; Hematologic Neoplasms ; therapy ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Interleukin-10 ; blood ; Interleukin-2 ; blood ; Interleukin-8 ; blood ; Male ; Middle Aged ; Tumor Necrosis Factor-alpha ; blood

Glycosylation, one of the most common and important reactions in biological systems, results in diverse functions and is often found in biologically active small-molecule natural products produced by microorganisms. Furthermore, sugar moieties are generally critical for their activities. Alternating the sugar structures thus provides the potentials for enhancing the biological activities of natural products, which evokes researchers to study the sugar biosynthetic machinery and its application in the modification of sugar moieties with an aim of generating unnaturally glycosylated natural product drugs with better activities. This review will briefly outline current studies on sugar biosynthesis and glycosyltransferase, with a few selected experiments designed to alter natural-product sugar structures.
Anthraquinones ; metabolism ; Biological Products ; chemistry ; metabolism ; Carbohydrates ; biosynthesis ; chemistry ; Erythromycin ; biosynthesis ; Glycosylation ; Glycosyltransferases ; biosynthesis ; Isomerism ; Molecular Structure ; Saccharopolyspora ; metabolism ; Streptomyces ; metabolism ; Synthetic Biology

BACKGROUNDThe antitumor role of Ras association domain family 1A (RASSF1A) gene and its potential molecular mechanisms are not well understood. The objective of this study was to observe the antitumor ability of RASSF1A in hepatocellular carcinoma, and study the mechanisms of cell apoptosis induced by RASSF1A.

METHODSAfter stably transfecting a RASSF1A (wild-type or mutant) expression vector into the BEL-7402 hepatocellular carcinoma cell line, RT-PCR and Western blotting was used to detect the RASSF1A expression levels in recombinant cells. The effects of wild-type RASSF1A on cell growth were observed in vitro by analyzing cell proliferation rate, cell colony formation, and in vivo by analyzing tumorigenesis in nude mice. In addition, the effect of RASSF1A gene expression on the chemosensitivity of human hepatocellular carcinoma cells to antitumor drugs was examined by inhibition of cell proliferation and the percentage of apoptotic cells.

RESULTSWild-type RASSF1A, not the mutant, suppressed cell growth in vitro and in vivo. Re-expression of wild-type RASSF1A could enhance the inhibition of cell proliferation and the percentage of apoptotic cells following cell treatment with mitomycin, but had no significant effect when combined with adriamycin, etoposide, 5-fluorouracil and cisplatin treatment.

CONCLUSIONWild-type RASSF1A inhibits cell growth and enhances cell chemosensitivity to mitomycin in hepatocellular carcinoma, suggesting that RASSF1A may serve as a new target for gene therapy in hepatocellular carcinoma patients.

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; genetics ; Blotting, Western ; Carcinoma, Hepatocellular ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Genetic Therapy ; methods ; Humans ; Mitomycin ; pharmacology ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Suppressor Proteins ; genetics ; metabolism ; physiology

This study was purposed to investigate the change of Th cell subsets in the patients with acute graft-versus host disease (aGVHD) and to explore its role in the pathogenesis of aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT). 23 patients underwent allo-HSCT were selected for analysis. The aGVHD in patients was diagnosed according to clinical features, and was confirmed by skin biopsy in some patients. The peripheral blood from 23 patients was collected before and after allo-HSCT. The quantitative chenges of Th1 and Th2 cells in peripheral blood samples were detected by using flow cytometry. The results showed that out of 23 patieats the aGVHD occured in 8 patients including 1 case of grade I, 2 case of grade II, 3 cases of grade III; no aGVHD occured in 15 patients. The flow cytometry analysis revealed that the amount of Th1 cells in patients with aGVHD was much higher than that in patients without aGVHD (p < 0.01), the IFN-gamma expression of Th1 cells in patients with aGVHD of grad II - III significantly was higher than that in patients without aGVHD (p < 0.01), meanwhie the IL-4 expression of Th2 cells in patients with aGVHD of grade II - III was significantly lower than that in patients without aGVHD (p < 0.05). Dynamical detection indicated that the Th1 obviously increased before occurrence of aGVHD and before treatment of aGVHD, while the Th1 cells obviously decreased after treatment of aGVHD. The Th1 cells not changed significantly in patients without aGVHD before and after allo-HSCT. It is concluded that Th1 cells obviously increase in patients with aGVHD, this increase is related to aGVHD pathogenesis. Detecting the changes of Th cell subsets in the early stage after allo-HSCT may be contributed to early diagnosis and therapy of aGVHD.
Graft vs Host Disease ; blood ; immunology ; Hematologic Neoplasms ; immunology ; therapy ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Th1 Cells ; immunology ; pathology