ABSTRACT
Pyroptosis is the process of inflammatory cell death. The primary function of pyroptosis is to induce strong inflammatory responses that defend the host against microbe infection. Excessive pyroptosis, however, leads to several inflammatory diseases, including sepsis and autoimmune disorders. Pyroptosis can be canonical or noncanonical. Upon microbe infection, the canonical pathway responds to pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), while the noncanonical pathway responds to intracellular lipopolysaccharides (LPS) of Gram-negative bacteria. The last step of pyroptosis requires the cleavage of gasdermin D (GsdmD) at D275 (numbering after human GSDMD) into N- and C-termini by caspase 1 in the canonical pathway and caspase 4/5/11 (caspase 4/5 in humans, caspase 11 in mice) in the noncanonical pathway. Upon cleavage, the N-terminus of GsdmD (GsdmD-N) forms a transmembrane pore that releases cytokines such as IL-1
ABSTRACT
Artemisinin is a preferred medicine in the treatment of malaria. In this study, AaCMK, a key gene involved in the upstream pathway of artemisinin biosynthesis, was cloned and characterized from Artemisia annua for the first time. The full-length cDNA of AaCMK was 1 462 bp and contained an ORF of 1 197 bp that encoded a 399-anomo-acid polypeptide. Tissue expression pattern analysis showed that AaCMK was expressed in leaves, flowers, roots and stems, but with higher expression level in glandular secretory trichomes. In addition, the expression of AaCMK was markedly increased after MeJA treatment. Subcellular localization showed that the protein encoded by AaCMK was localized in chloroplast. Overexpression of AaCMK in Arabidopsis increased the contents of chlorophyll a, chlorophyll b and carotenoids. These results suggest that AaCMK plays an important role in the biosynthesis of terpenoids in A. annua and this research provids a candidate gene that could be used for engineering the artemisinin biosynthesis.
ABSTRACT
[Objective]To study the effects of Caspase-1 specific inhibitor AC-YVAD-CMK on intimal hyperplasia after carotid artery balloon injury in rats and its possible mechanism.[Methods]A total of 33 male adult SD rats were randomly divided into sham group,balloon injury group and balloon injury+AC-YVAD-CMK group. Using the method of balloon injury to establish rat carotid ar?tery intimal hyperplasia animal model,rats were sacrificed and blood vessels were harvested 14 days after operation. Fifteen vascular segments embedded in OCT and the intima to media(I/M)area ratio of neointima was measured by hematoxylin-eosin(HE)staining;18 vascular segments were harvested and the expression of NLRP3 inflammasome,cleaved-Caspase-1,interleukin(IL)-1βand IL-18 were measured by Western blot.[Results]HE staining showed that AC-YVAD-CMK significantly inhibited the degree of intimal hyperplasia compared with the balloon injury group[(0.78 ± 0.13)vs(1.52 ± 0.14);P=0.000]. The expression of NLRP3 inflamma?some was increased in balloon injury group while the AC-YVAD-CMK attenuates the expression of NLRP3(P=0.009);The expres?sion of cleaved-Caspase-1 was in line with the expression of NLRP3(P=0.000). The levels of pro-inflammatory cytokines IL-1βand IL-18 in balloon injury+AC-YVAD-CMK group were significantly lower than those in the balloon injury group(P=0.000).[Conclusion]AC-YVAD-CMK can attenuate intimal hyperplasia after balloon injury of carotid artery in rats,which might be related to its effect on inhibiting the activation of Caspase-1,which could affect the release of pro-inflammatory cytokine of IL-1βand IL-18.
ABSTRACT
The 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase was the fourth key enzymes in plant terpenoid biosynthesis pathway of methyl erythritol phosphate pathway(MEP). According to the study of Cinnamomum camphora transcriptome data,we abtained the 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase gene using RT-PCR,and named CcCMK1,then deposited it in GeneBank(Accession number： Ku376098).Bioinformatics analysis showed the open reading frame (ORF) of the CcCMK1 was 1 212 bp.The putative protein encoded 403 amino acids,and its molecular weight was 44.46 kDa and theoretically isoelectric point was 4.99.Transmembrane structure analysis showed that there was no transmembrane structure. Signal peptide analysis showed that it was a non secretory protein, and there was no signal peptide. The subcellular localization showed that the chloroplast was located in the chloroplast.Analysis of the expression of CcCMK1 gene in five chemotypes of C. camphora using Real-time PCR showed its expression level was highest in C. longepaniculatum, and the lowest in Borneol camphor.This research provided a basis for characterizing the key enzyme genes of terpenoid biosynthetic pathway in C. camphora.
ABSTRACT
Objective:To determine the expansion and differentiation effect of Staurosporine on human megalaryoblastic cell line(CMK).Methods:With MTT and colony assaies.Results:Staurosporine could densitily inhibited the expansion of CMK cell,IC 50 was 50 nmol/L,Staurosporine could inhibite CMK cell at G 1 phase,then decreased the cells of S and G 2M phases,ST in 80 nmol/L improve the expression of CD41 antigen in CMK cell,induce its differentiation.Conclusion:ST as a new kind of anti-tumor facor has different mechanism with other anti-tumor drugs. [