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The aim of this study was to observe the effect of p38MAPK inhibitor SB203580 on ATRA-induced differentiation of NB4 cells. The proliferation activity of cells was assayed by MTT method, the cell cycle was detected by flow cytometry, the differentiation of NB4 cells into granulocytes was measured by test of NBT reduction, the activity of extracellular signal-regulated kinase (ERK) was detected by substrate phosphorylation. The results showed that the ATRA in 0.01-01 micromol/L inhibited the proliferation of NB4 cells in time-and dose-dependent manner and induced the differentiation of NB4 cells into myeloid; the ATRA stimulated ERK activity in this process; ERK inhibitor PD98059 could partially block ATRA effect, specific inhibitor of p38MAPK, SB203580, combined with ATRA also could partially block the effects of ATRA on inhibition of NB4 growth and induction of differentiation. It is concluded that the ATRA stimulates ERK and p38MAPK pathway in the process inducing differentiation of NB4 cells, the ERK and P38MAPK may be necessary for the ATRA-induced differentiation in NB4 cells.

Objective: To investigate the effect of bufalin combined with all-trans retinoic acid-induced (ATRA) differentiation of acute promyelocytic leukemia (APL) cells in primary culture., Methods: Fresh leukemia cells were obtained from heparinized bone marrow aspirations of 12 newly diagnosed APL patients. Cell viability was determined by trypan blue dye exclusion. Apoptosis of APL cell was assessed by morphological analysis. Differentiation of APL cell was also assessed by morphological analysis. Nitro blue tetrazolium (NBT) reduction test and expression of the granulocyte/macrophage-specific antigen CD(11)b was carried out with flow cytometric assay., Results: Bufalin combined with ATRA can induce differentiation of APL cells towards mature stages, NBT reduction was increased 15% - 52% and CD(11)b expression was also increased 16% - 69% in combination of bufalin and ATRA as compared with that of ATRA alone, while the concentration of ATRA needed in the combination group was reduced to 30% and the time of differentiation was reduced from 7 days to 4 days., Conclusion: The combination of ATRA with bufalin can significantly enhance the differentiation of acute promyelocytic leukemia cells in primary culture by ATRA.

Background: Osteoarthritis (OA) is caused by a complex set of pathophysiological factors. The genetic factors involved in the occurrence and progress of the disease have been widely discussed by scholars. It was found that growth differentiation factor 5 (GDF5) gene polymorphisms may be linked to OA susceptibility, which has been controversial and needs to be further confirmed by an updated meta-analysis. Objectives: We examined the association between GDF5 rs143383 single nucleotide polymorphism (SNP) and OA susceptibility. Methods: All relevant articles that met the criteria are retrieved and included, and the search deadline is June 2022. The allele frequencies and different genotype frequencies of GDF5 rs143383 loci in each study were extracted and statistically analyzed by R4.1.3 software, and the different genetic models were analyzed based on their odds ratio (OR) and 95% confidence interval (CI). Results: The meta-analysis explained that GDF5 rs143383 SNP was crucial correlated with OA in all patients with OA of knee, hip and hand. The codominant gene model in the whole crowd (OR = 1.17, 95% CI 1.07–1.27, P < 0.01) enlightened that OA was vitally associated with GDF5 gene polymorphism. At the same time, we did a subgroup analysis based on ethnicity. The codominant gene model (OR = 1.31, 95% CI 1.12–1.53, P < 0.01) in Asian population, the codominant homozygote model (OR = 1.28, 95% CI 1.14–1.43), codominant heterozygote gene model (OR = 1.12, 95% CI 1.01–1.23, P = 0.02), and dominant gene model (OR = 1.19, 95% CI 1.09–1.31, P < 0.01) in Caucasian are analyzed by subgroup analysis. It means that there is a momentous relationship between the GDF5rs143383 gene polymorphism and OA, especially among Caucasians. In addition, we also discussed different types of OA separately and discover that the GDF5rs143383 gene polymorphism was relevant for knee osteoarthritis (KOA) and hand osteoarthritis, and it was more significant in the Caucasian population. But due to the high heterogeneity in hip osteoarthritis, it could not be accurately concluded. Furthermore, we also analyzed the osteoarthritis of different genders and found that the GDF5 rs143383 SNP was associated with both men and women and was still significant in the Caucasian population. Conclusion: We found a close association between osteoarthritis and GDF5rs143383SNP in this study. From the analysis of each group, we got the same conclusion in KOA and hand OA, but which need further verification in hip OA. Considering gender, we found a close relationship between GDF5 rs143383 SNP and OA of the knee, hip and hand, both for men and women. This conclusion is more obvious in Caucasian people. [ABSTRACT FROM AUTHOR]