Several evidences support the idea that a small population of tumour cells representing self‐renewal potential are involved in initiation, maintenance, metastasis, and outcomes of cancer therapy. Elucidation of microRNAs/genes regulatory networks activated in cancer stem cells (CSCs) is necessary for the identification of new targets for cancer therapy. The aim of the present study was to predict the miRNAs pattern, which can target both metastasis and self‐renewal pathways using integration of literature and data mining. For this purpose, mammospheres derived from MCF‐7, MDA‐MB231, and MDA‐MB468 were used as breast CSCs model. They had higher migration, invasion, and colony formation potential, with increasing in stemness‐ and EMT‐related genes expression. Our results determined that miR‐204, ‐200c, ‐34a, and ‐10b contemporarily could target both self‐renewal and EMT pathways. This core regulatory of miRNAs could increase the survival rate of breast invasive carcinoma via up‐regulation of OCT4, SOX2, KLF4, c‐MYC, NOTCH1, SNAI1, ZEB1, and CDH2 and down‐regulation of CDH1. The majority of those target genes were involved in the regulation of pluripotency, MAPK, WNT, Hedgehog, p53, and transforming growth factor β pathways. Hence, this study provides novel insights for targeting core regulatory of miRNAs in breast CSCs to target both self‐renewal and metastasis potential and eradication of breast cancer. 相似文献
This study aimed to evaluate proposed molecular markers related to eye limbal stem cells (SC) and to identify novel associated genes. The expression of a set of genes potentially involved in stemness was assessed in freshly prepared limbal, corneal and conjunctival tissues. PAX6, AC133, K12 and OCT4 were detected in all the tissues and p63(+)/K3(-)/K12(+)/Nodal(+)/Cx43(+) were expressed in conjunctival, p63(-)/K3(+)/K12(+)/Nodal(-)/Cx43(+) in corneal, and p63(+)/K3(-)/K12(-)/Nodal(-)/Cx43(-) in limbal tissues. Limbal explants were cultured on human amniotic membrane for 21 days. The cells expressed p63 but not K3, K12, Nodal and Cx43, however, the expression of K3, K12 and Cx43 was detected, and p63 and the high BrdU-labeling index decreased with more culture. Ultrastructure analysis of the cultured cells showed typically immature organization of intracellular organelles and architecture. Our data suggest that limbal, corneal and conjunctival tissues are heterogeneous with some progenitors. Also, the expression of traditional SC markers may not be a reliable indicator of limbal SC and there is an increasing need to determine factor(s) involved in their stemness. 相似文献
Nigella sativa (N. sativa) exhibits anti-inflammatory, antioxidant, antidiabetic, antimetastatic and antinociceptive effects and has been used to treat dozens of diseases. Thymoquinone (TQ) is an important and active component isolated from N. sativa seeds. Inhibition of cancer-associated activating PIK3CA mutations is a new prospective targeted therapy in personalized metastatic breast cancer (MBC). TQ is reported to be an effective inhibitor of the PI3K/Akt1 pathway in MBC. This study aimed to evaluate the in vitro antitumor effect of TQ in the context of two PIK3CA hotspot mutations, p. H1047R and p. H1047L.
Methods and results
Molecular dynamics, free energy landscapes and principal component analyses were also used to survey the mechanistic effects of the p. H1047R and p. H1047L mutations on the PI3K/Akt1 pathway. Our findings clearly confirmed that the p. H1047R and p. H1047L mutants could reduce the inhibitory effect of ΔNp63α on the kinase domain of PIK3CA, resulting in increased activity of PI3K downstream signals. Structurally, the partial disruption of the interaction between the ΔNp63α DNA binding domain and the PIK3CA kinase domain at residues 114–359 and 797–1068 destabilizes the conformation of the activation loop and modifies the PIK3CA/ΔNp63α complex. Alongside these structural changes, we found that TQ treatment resulted in high PI3K/Akt1 pathway inhibition in p. H1047R and p. H1047L-expressing cells versus wild-type cells.
Conclusions
These two PIK3CA hotspot mutations therefore not only contribute to tumor progression in patients with MBC but may also serve as targets for the development of novel small molecule therapeutic strategies.
Given that N-methylmorpholine-N-oxide (NMMO) is a promising alternative for the pretreatment of lignocelluloses, a novel process for ethanol and biogas production from wood was developed. The solvent, NMMO, is concentrated by multistage evaporation, and the wood is pretreated with the concentrated NMMO. Thereafter, ethanol is produced by the non-isothermal simultaneous saccharification and fermentation (NSSF) method, which is a rapid and efficient process. The wastewater is treated by upflow anaerobic sludge blanket (UASB) digester for rapid production of biogas. The process was simulated by Aspen plus®. Using mechanical vapor recompression for evaporators in the pretreatment and multi-pressure distillation columns, the energy requirements for the process were minimized. The economical feasibility of the developed biorefinery for five different plant capacities was studied by Aspen Icarus Process Evaluator. The base case was designed to utilize 200,000 tons of spruce wood per year and required M€ 58.3 as the total capital investment, while the production cost of ethanol is calculated to be €/l 0.44. 相似文献
Thyroid peroxidase (TPO) gene variations are one cause of thyroid autoimmune diseases. The aim of this study was to examine the association between the T1936C, T2229C and A2257C polymorphisms of the TPO gene and Anti-TPO level.
Materials and methods
In this case–control study, 188 individuals (86 males and 102 females), aged 20–80 years, were randomly selected from among the Tehran Lipid and Glucose Study (TLGS) population. A2257C and T2229C SNPs were detected with RFLP by use of BsrI and Eco57I as the restriction enzymes respectively, while the T1936C SNP was determined with ARMS-PCR.
Results
In the presence of the C allele of T1936C, Anti-TPO level was significantly increased (CC: 238 ± 43.3, CT: 47.7 ± 15.9, TT: 74.1 ± 11.3 IU/L p = 0.002); however, this association was attenuated after adjustment for sex and age (p = 0.059). No significant difference, before and after adjustment, was found in Anti-TPO level in the presence of T2229C SNP (CC: 129.1 ± 24.5, CT: 43.5 ± 12.6, TT: 126.5 ± 13.8 IU/L p = 0.196). The association between A2257C and Anti-TPO level was only significant after adjustment for potential confounders (p = 0.007). The association between ATC and CTT haplotypes and Anti-TPO level was significant (p = 0.023, 0.021 respectively), the association between CTT and Anti-TPO concentration was also significant after adjustment for sex (p = 0.014).
Conclusion
The results of the present study confirmed the association between TPO gene polymorphisms and Anti-TPO level in the Tehranian population. 相似文献
Previously, an extracellular α-amylase (BKA) had been purified from the culture of Bacillus sp. KR8104. Subsequently, the crystal structure of the active enzyme revealed a 422 amino acids polypeptide. In this study, the bka was cloned into E. coli, which encoded a polypeptide of 659 amino acids including two additional fragments: one 44 residues N-terminal fragment and another 193 residues C-terminal fragment. In order to investigate the role of the C-terminal fragment, two constructs with and without this region [BKAΔ(N44) and BKAΔ(N44C193)] were designed and expressed in E. coli BL21. The optimum pH, thermal stability, and the end-products of starch hydrolysis were found to be similar in both constructs. The Km and V(max) values for BKAΔ(N44) were lower than BKAΔ(N44C193), using either starch or ethylidene-blocked 4-nitrophenylmaltoheptaoside as a substrate. 相似文献
We evaluated the effects of starvation and refeeding on digestive enzyme activities in juvenile roach, Rutilus rutilus caspicus. Fish were divided into four feeding groups (mean mass 1.68 ± 0.12 g). The control group was fed to satiation twice a day throughout the experiment with formulated diet (SFK). The other three groups were deprived of feed for 1(S1), 2(S2), and 3(S3) weeks, respectively, and then fed to satiation during the refeeding period. The results showed that trypsin specific activity was not affected significantly either by starvation or refeeding, in all experimental groups. Chymotrypsin specific activity did not change significantly in S1 fish during the experimental period. In S2 and S3 fish no significant changes were observed during the starvation period. Upon refeeding, the activity increased in S2 fish, while it decreased in S3 fish. Amylase specific activity decreased significantly during the starvation period in all experimental groups. Upon refeeding, the activity increased. Alkaline phosphatase specific activity did not change significantly during the experiment period in S3 fish, while it showed significant changes during the starvation and refeeding period in the S1 and S2 fish. Starvation also had a significant effect on the structure of the intestine. 相似文献