Functional R2R3-MYB Transcription Factor NsMYB1, Regulating Anthocyanin Biosynthesis, Was Relative To The Fruit Color Differentiation in Nitraria Sibirica Pall

Background Nitraria sibirica Pall. is an economic plant with two kinds of fruit color, widely spreads in the Qinghai Tibet Plateau. The chemical analysis and pharmacological evaluation had been carried out for several tens of years, the mechanism behind the fruit color differentiation is still unclear. Results In this manuscript, the chemical analysis of the extractions showed that the chemical composition of fruit color was anthocyanin, and two kind of Nitraria sibirica Pall. were caused by the content differentiation with the same anthocyanin kinds. Cya-nidin-3-[2ʹ’-(6ʹ’’-coumaroyl)-glucosyl]-glucoside (C3G) was the major anthocyanin. Transcriptome analysis and the qRT-PCR revealed that the structural genes relative to anthocyanin biosynthesis except CHS, F3’5’H and ANS were up-regulated in BF compared with RF, which indicated that transcript factor should be the reason for the expression difference of the structure genes. In the unigenes of the transcript factor MYB and bHLH, relative to anthocyanin, only NsMYB1 (Clus-ter-8422.10600), was high-expression and up-expression in the BF. NsMYB1 encoded the same length protein with four amino acid differences in the RF and BF, and both contained the intact DNA, HTH-MYB and SANT domains. NsMYB1 was close to the AtMYB114, AtMYB113 and AtPAP1, regulating anthocyanin biosynthesis, in phylogenetic relationship. Both NsMYB1r and NsMYB1b could promote the transcript of the structural genes, and induced the anthocyanin accumulation in all tissues of transgenic tobacco. The insertion of ‘TATA’ in the promoter of NsMYB1r gave one more promoter region, and was the reason for higher transcripts in black fruit possibly. Conclusions NsMYB1 was a functional R2R3-MYB transcription factor, regulated the anthocyanin biosynthesis, and leaded to the fruit color differentiation in Nitraria sibirica Pall.

A novel Lnc408 maintains breast cancer stem cell stemness by recruiting SP3 to suppress CBY1 transcription and increasing nuclear β-catenin levels

Tumor initiation, development, and relapse may be closely associated with cancer stem cells (CSCs). The complicated mechanisms underlying the maintenance of CSCs are keeping in illustration. Long noncoding RNAs (lncRNAs), due to their multifunction in various biological processes, have been indicated to play a crucial role in CSC renewal and stemness maintenance. Using lncRNA array, we identified a novel lncRNA (named lnc408) in epithelial–mesenchymal transition-related breast CSCs (BCSCs). The lnc408 is high expressed in BCSCs in vitro and in vivo. The enhanced lnc408 is critical to BCSC characteristics and tumorigenesis. Lnc408 can recruit transcript factor SP3 to CBY1 promoter to serve as an inhibitor in CBY1 transcription in BCSCs. The high expressed CBY1 in non-BCSC interacts with 14-3-3 and β-catenin to form a ternary complex, which leads a translocation of the ternary complex into cytoplasm from nucleus and degradation of β-catenin in phosphorylation-dependent pattern. The lnc408-mediated decrease of CBY1 in BCSCs impairs the formation of 14-3-3/β-catenin/CBY1 complex, and keeps β-catenin in nucleus to promote CSC-associated CD44, SOX2, Nanog, Klf4, and c-Myc expressions and contributes to mammosphere formation; however, restoration of CBY1 expression in tumor cells reduces BCSC and its enrichment, thus lnc408 plays an essential role in maintenance of BCSC stemness. In shortly, these findings highlight that the novel lnc408 functions as an oncogenic factor by recruiting SP3 to inhibit CBY1 expression and β-catenin accumulation in nucleus to maintain stemness properties of BCSCs. Lnc408–CBY1–β-catenin signaling axis might serve as a new diagnostic and therapeutic target for breast cancer.

Icariin-Functionalized Nanodiamonds to Enhance Osteogenic Capacity In Vitro

Nanodiamonds (NDs) have been used as drug delivery vehicles due to their low toxicity and biocompatibility. Recently, it has been reported that NDs have also osteogenic differentiation capacity. However, their capacity using NDs alone is not enough. To significantly improve their osteogenic activity, we developed icariin (ICA)-functionalized NDs (ICA-NDs) and evaluated whether ICA-NDs enhance their in vitro osteogenic capacity. Unmodified NDs and ICA-NDs showed nanosized particles that were spherical in shape. The ICA-NDs achieved a prolonged ICA release for up to 4 weeks. The osteogenic capacities of NDs, ICA (10 μg)-NDs, and ICA (50 μg)-NDs were demonstrated by alkaline phosphatase (ALP) activity; calcium content; and mRNA gene levels of osteogenic-related markers, including ALP, runt-related transcript factor 2 (RUNX2), collagen type I alpha 1 (COL1A1), and osteopontin (OPN). In vitro cell studies revealed that ICA (50 μg)-ND-treated MC3T3-E1 cells greatly increased osteogenic markers, including ALP, calcium content, and mRNA gene levels of osteogenic-related markers, including ALP, RUNX2, COL1A1, and OPN compared to ICA (10 μg)-NDs or ND-treated cells. These our data suggest that ICA-NDs can promote osteogenic capacity.

Cerebrovascular and neurological impact of chronic smoking on post traumatic brain injury outcome and recovery: an in vivo study

Background: Traumatic Brain Injury (TBI) is among the most prevalent causes of cerebrovascular and neurological damage worldwide. To this end, tobacco smoking (TS) has been shown to promote vascular inflammation, neurovascular impairments and risk of cerebrovascular and neurological disorders through oxidative stress (OS) stimuli targeting the blood-brain barrier (BBB) endothelium among others. It has been recently suggested that premorbid conditions such as TS may exacerbate post-TBI brain damage and impact recovery. The present study aims to investigate and dissect out the pathophysiological mechanisms underlying the exacerbation of TBI in a weight-drop model following chronic TS exposure. Methods: C57BL/6J male mice, age range 6–8 weeks were chronically exposed to TS for three weeks. Test animals were then subjected to TBI by guided vertical head weight drop using a 30 g metal weight free felling from an 80 cm distance before reaching the target. Physical activity and body weight of the mice were analyzed before TBI and 1 h, 24 h and 3 days post-injury. Finally, mice were sacrificed to collect blood and brain samples for subsequent biochemical and molecular analysis. Western blotting was applied to assess the expression of Nrf2 (a key antioxidant transcription factor) as well as tight junction proteins associated with BBB integrity including, ZO-1, Occludin, Claudin-5 from brain tissues homogenates. Levels of NF-kB (a pro-inflammatory transcript factor which antagonizes Nrf2 activity) along with pro-inflammatory cytokines IL-6, IL-10 and TNF-α were measured by ELISA on blood samples. Results: TS promoted significantly increased inflammation and loss of BBB integrity in TBI when compared to TS-Free test mice. Additionally, mice chronically exposed to TS prior to TBI experienced a more significant weight loss, behavioral, and motor activity deficiency and slower post-TBI recovery when compared to TS-free TBI mice. Conclusion: TS promotes a significant exacerbation of post-TBI neurovascular and neurological impairments. Whereas BBB impairment and pro-inflammatory vascular responses induced by chronic TS exposure are likely responsible for the retardation of post-traumatic recovery observed in these animals.