ClyA enhances LPS-induced IL-1ß secretion in human macrophages through TLR4 and NLRP3 signaling.

Lipopolysaccharide (LPS) plays an important role in tumor suppression by activating macrophages. After macrophages activation, a trail of cytokines was secreted, including IL-1ß. Previous studies reported that the anti-tumor function of IL-1ß is concentration-dependent, and increasing the level of IL-1ß will enhance its anti-tumor effect. Cytolysin A (ClyA), a member of the protein family called pore-forming toxins (PFTs), is secreted by Gram-negative bacteria, which has a potential role in enhancing the secretion of IL-1ß. In this study, the function of Cytolysin A was evaluated by investigating its ability to induce innate immune responses in macrophages and the signaling pathway(s) involved in LPS-induced production of IL-1ß. The production of IL-1ß was highly enhanced when the macrophages were treated with LPS and ClyA together. The production of IL-1ß was regulated by TLR4-MyD88-IL-1ß pathway and NLRP3-ASC-Caspase1-IL1ß pathway. By treating the colon cancer cell line CT26 with the conditioned medium, the proliferation of CT26 cells was inhibited and the apoptosis of CT26 cells was increased. In conclusion, this study indicated that ClyA enhances the production of IL-1ß induced by LPS in human macrophages. The proliferation of CT26 cells was inhibited and the apoptosis was increased when being treated with the macrophage-conditioned media, which provides a feasible treatment for colon tumor.

Effect of variation of ABCB1 and GSTP1 on osteosarcoma survival after chemotherapy.

We conducted a comprehensive study to investigate the role of genes involved in metabolic and transport pathways in response to chemotherapy and clinical outcome of osteosarcoma patients. Genotyping of seven gene polymorphisms was performed on a 384-well plate format on the Sequenom MassARRAY platform in 162 patients with osteosarcoma. We studied the correlation of the seven gene polymorphisms with response to chemotherapy and clinical outcome of patients. Individuals with the ABCB1 TT genotype had a higher probability of responding poorly to chemotherapy, indicated by an odds ratio (OR) of 2.64 (95%CI=1.04-6.83). Similarly, the genotype of GSTP1 GG was significantly associated with improved responses to chemotherapy, indicated by an OR of 3.33 (95%CI=1.26-8.99). The ABCB1 TT and GSTP1 GG genotypes were significantly associated with a shorter overall survival (OS). Our study found that two gene polymorphisms in two transporter genes and one Phase II metabolism enzymes are associated with response to chemotherapy and OS in osteosarcoma patients, suggesting the potential of the two gene polymorphisms as prognostic biomarkers for osteosarcoma.

Effect of bradykinin on renal mesangial cell proliferation and extracellular matrix secretion.

Recent studies have found that bradykinin (BK) plays a role in delaying glomerulosclerosis, although the mechanism of this phenomenon remains unclear. Mesangial cell proliferation (MCP) and extracellular matrix (ECM) secretion are important mechanisms for glomerulosclerosis. This study investigated the impact of BK on the platelet-derived growth factor (PDGF)-induced proliferation of mesangial cells, and evaluated its correlations with the extracellular signal-related kinase (ERK) signaling pathway. The results showed that on its own, 10-1000 mg/L BK promoted MCP and ECM secretion and induced ERK phosphorylation. However, BK administration after PDGF pre-incubation inhibited PDGF-induced MCP, ECM secretion, and ERK phosphorylation. The BK B2 receptor-specific antagonist, HOE-140, and tyrosine phosphatase inhibitor (OV) effectively blocked the function of BK. In summary, these results demonstrated that BK has a bidirectional effect on MCP and ECM secretion: when used alone, it promoted effects on these phenomena, but these effects were inhibited when combined with PDGF. This suggests that the role of BK might be achieved through inhibiting activation of the PDGF-induced ERK1/2 pathway.

[Lumbosacral lipomas with spinal bifida].

Spinal dysraphism is usually accompanied with lumbosacral lipoma. The neurological deficits such as lower extremities sensorimotor disturbances, bowel and bladder dysfunction are produced by tethering, compression of lipoma and direct transmission of external force on the spinal cord during growth period. 25 patients treated surgically at our hospital between May, 1985, and January, 1993, were reviewed. Surgical approach was designed for debulking the lipomatous mass, untethering and decompressing the cord, repairing the dural defect and paraspinal muscle cleft. 2-59 months (mean 37.5 mons) after operation the 2 patients whose neurological system were normal before operation remained intact. In other 23 patients, bowel function recovered in 75%, active urination restored and improved in 66.2%. Motor dysfunction and paresthesia of the lower extremities alleviated in 78.3%. A case of mild uremia returned to normal and another moderate case improved. None was deteriorated by the operative procedure except one case in which a posterior nerve root was injured.

[Treatment of neuromyelopathy after repair of myelomeningocele or meningocele].

Forty-two cases of neuromyelopathy after lower thoracic lumbosacral myelomeningocele or meningocele repairment were reported. The repaired ages were from newborn to 6 years old. Subsequently progressive paralysis of lower extremities with incontinence of bowel and urination were seen after the primary operation. It may be due to "tethered spinal cord syndrome" or postoperative adhesion. Removal of the scar of adhesions over the lower thoracic and lumbosacral region and neurolysis were performed. Following 3-30 months after operation we found out that recovery of bowel function in 38 cases (90.5%). Active urination was recovered in 13 cases (31%) and improved in 22 cases (52.4%). Motor dysfunction and paresthesis of the lower extremities were alleviated in 19 (73.1%) of the 27 cases. No case revealed aggravation of symptom due to operative procedure.