Comparative Analysis of the Biosimilar and Innovative G-CSF Modulated Pathways on Umbilical Cord Blood-Derived Mononuclear Cells.

Biosimilars of granulocyte colony-stimulating factor (G-CSF) have been routinely introduced into clinical practice. However, not functional genomics characterization has been performed yet in comparison with the innovator G-CSF. This study aimed to evaluate the transcriptomic changes in an in vitro model of umbilical cord blood cells (UBC) exposed to G-CSF for the identification of their modulated pathways. Umbilical cord blood cells-derived mononuclear cells (MNCs) were treated with biosimilar and innovator G-CSF for further gene expression profiling analysis using a microarray-based platform. Comparative analysis of biosimilar and innovator G-CSF gene expression signatures allowed us to identify the most commonly modulated pathways by both drugs. In brief, we observed predominantly upmodulation of transcripts related to PI3K-Akt, NF-kappaB, and tumor necrosis factor (TNF) signaling pathways as well as transcripts related to negative regulation of apoptotic process among others. In addition, hematopoietic colony-forming cell assays corroborate the G-CSF phenotypic effects over UBC-derived MNCs. In conclusion, our study suggests that G-CSF impacts UBC-derived cells through the modulation of several signaling pathways associated with cell survival, migration, and proliferation. The concordance observed between biosimilar and innovator G-CSF emphasizes their similarity in regards to their specificity and biological responses.

Las células madre, piedra angular de rejuvenecimiento. Aclarando conceptos / Stem cells, corners stone of rejuvenescence. Clarifying concepts

Las células madre tienen tres características comunes: la autorrenovación, la indiferenciación y la derivación a cualquier célula madura, éstas son el patrimonio (en el caso de las célula madre adultas) con el que cuenta un individuo para regenerar las células senescentes a lo largo de la vida. Las células madre pueden regenerar tejidos en individuos compatibles de la misma especie. El termino célula madre en tecnología cosmética hace referencia principalmente a sustancias extraídas de células madre de origen vegetal, ricas en polifenoles tales como el resveratrol, y luteolina o péptidos capaces de activar los genes de las sirtuinas NAD dependientes, que producen de acetilación del ADN que permiten la compactación de la cromatina (AU)

Stem cells has three common characteristics: self-renewal, differentiation and derivation of any mature cell, these are the assets (in the case of adult stem cell) with which an individual has to regenerate senescent cells along life. Stem cells can regenerate tissue compatible individuals of the same species. In Cosmetic technology the term stem cell refers mainly to stem cells extracted from substances of vegetable origin, rich in polyphenols such as resveratrol, and luteolin or peptides able to activate the genes of the NAD-dependent sirtuins, which produce deacetylation that allow the compaction of chromatin (AU)

Linkage disequilibrium of HLA-DR3 and HLA-DR4 with HLA-B alleles in Mexican patients with rheumatoid arthritis.

OBJECTIVE: We studied the gene frequencies of classes I, II and III antigens of the Major Histocompatibility Complex (MHC) in 32 Mexican mestizo patients with rheumatoid arthritis (RA) and compared them with those obtained from 110 of their first degree relatives and 100 Mexican mestizo controls. Furthermore, we analyzed the observed and expected frequencies of the haplotypes and calculated the delta values in the three groups. METHODS: The class I and class II MHC antigens were determined by the microlymphocytotoxicity test; class III MHC antigens were obtained by high voltage agarose gel electrophoresis and immunofixation. The significance of differences among the three groups was tested by chi-square analysis; linkage disequilibrium among the different alleles in each haplotype was estimated by computing the delta values (observed vs expected frequencies). RESULTS: Patients showed a significantly increased frequency of HLA-A1 (corrected p = 10(-5)), DR3 (corrected p = 0.04) and DQ2 (corrected p = 10(-4)) and a decreased frequency of A31 (corrected p = 0.003) as compared to the normal controls. First degree relatives compared to patients and controls showed a decreased frequency of HLA-DR4 (corrected p = 0.02 and 0.008 respectively); consequently, DQ3 was also diminished (corrected p = 10(-4)). Analysis of MHC haplotypes within families revealed in the patients seven MHC haplotypes with significant differences between the observed and expected frequencies (statistically significant delta values). These haplotypes were: [HLA-B8; DR3], [HLAB44; FC31], [HLA-B8; SC42], [HLA-DR4; SC31], [HLA-B35; SC32], [HLA-DR7; FC31] and [HLA-DR2; SC31]. On the other hand, the control haplotypes showed significant delta values in only one of these haplotypes ([HLA-DR4; SC31]), whereas first degree relatives showed none. Analysis of all the class I, II and III alleles, either alone or as part of specific haplotypes, showed two B-DR haplotypes with higher relative risks than their alleles alone. These haplotypes were: [B44; DR4] (RR = 6.0, p = 0.005), and [B8; DR3] (RR = 8.3, p = 0.010). CONCLUSION: The results suggest that a specific combination of antigens in the same haplotype (for instance between HLA-B and HLA-DR) could contribute to increasing the genetic susceptibility to develop RA.