Pirh2 mediates the sensitivity of myeloma cells to bortezomib via canonical NF-κB signaling pathway

Clinical success of the proteasome inhibitor established bortezomib as one of the most effective drugs in treatment of multiple myeloma (MM). While survival benefit of bortezomib generated new treatment strategies, the primary and secondary resistance of MM cells to bortezomib remains a clinical concern. This study aimed to highlight the role of p53-induced RING-H2 (Pirh2) in the acquisition of bortezomib resistance in MM and to clarify the function and mechanism of action of Pirh2 in MM cell growth and resistance, thereby providing the basis for new therapeutic targets for MM. The proteasome inhibitor bortezomib has been established as one of the most effective drugs for treating MM. We demonstrated that bortezomib resistance in MM cells resulted from a reduction in Pirh2 protein levels. Pirh2 overexpression overcame bortezomib resistance and restored the sensitivity of myeloma cells to bortezomib, while a reduction in Pirh2 levels was correlated with bortezomib resistance. The levels of nuclear factor-kappaB (NF-κB) p65, pp65, pIKBa, and IKKa were higher in bortezomib-resistant cells than those in parental cells. Pirh2 overexpression reduced the levels of pIKBa and IKKa, while the knockdown of Pirh2 via short hairpin RNAs increased the expression of NF-κB p65, pIKBa, and IKKa. Therefore, Pirh2 suppressed the canonical NF-κB signaling pathway by inhibiting the phosphorylation and subsequent degradation of IKBa to overcome acquired bortezomib resistance in MM cells.

Progress in resistin and type 2 diabetes as well as obesity / 中国病理生理杂志

A Review Resistin, a new hormone found in the year 2001 and secreted by adipocytes, is related to type 2 diabetes and obesity. It brings some hope to solve the medical hamper of insulin resistance. The resistin discovery, molecule structure, function and expression, secretion regulation as well as gene polymorphism are reviewed in the article. [

Relationship between IL-1 gene polymorphism and severity of rheumatoid arthritis and secretion of IL-1 / 中国病理生理杂志

AIM: To determine the influence of interleukin-1?(IL-1?) and ?(IL-1?) gene polymorphisms on rheumatoid arthritis(RA) disease severity and secretion of IL-1?. METHODS: The study included 136 RA patients and 102 healthy controls. PCR-RFLP was used to detect site mutation at IL-1 gene. Meanwhile the IL-1? was also measured in the supernatant of the cultured and stimulated peripheral blood mononuclear cells(PBMC). RESULTS: No difference in the allele frequencies or genotypes of the IL-1? gene polymorphisms was found between the controls and RA patients.IL-1? allele 2 was overrepresented in patients with erosive RA but not in nonerosive patients. The patients with IL-1? allele 2 had a higher swollen joint index, higher tender joint index and erythrocyte sedimentation rate than those without IL-1? allele 2.The IL-1? in supernatant of stimulated PBMC from patients with IL-1? allele 2 had a higher level than that from those without allele 2. CONCLUSION: IL-1 gene polymorphisms may influence the occurrence of RA. Detection of IL-1? allele 2 have a potential prognostic value in RA.

Influence of IL-1? gene polymorphism on the transcription of IL-1? mRNA in patients with rheumatoid arthritis / 中国病理生理杂志

AIM: To investigate the effect of IL-1 gene polymorphism on the expression of IL-1? mRNA in patients with rheumatoid arthritis. METHODS: The method of FQ-RT-PCR was used to detect the expression of IL-1? mRNA in peripheral blood mononuclear cells separated from rheumatoid arthritis patients with different IL-1? genotype. RESULTS: The expression levels of IL-1? mRNA in 20 patients who carried IL-1? 2*2 genotype were higher than patients who carried no 2*2 genotype and normal subjects. Significant difference existed among three groups. CONCLUSION: IL-1? gene polymorphism influences the transcription of IL-1?. [