Fluorescent carbon dots derived from urine and their application for bio-imaging.

This study aims to obtain water-soluble fluorescent carbon dots (C-dots) from low-value metabolites through a simple, economical, one-step synthetic route. The urine C-dots (UCDs) and hydrothermally treated urine C-dots (HUCDs) were obtained, respectively, using straightforward Sephadex filtration method from human adults and hydrothermal reaction method. The UCDs and HUCDs emit fluorescence upon being excited with ultraviolet light with a quantum yield of 4.8% and 17.8%, respectively. TEM analysis revealed that UCDs and HUCDs had an average size of 2.5 nm and 5.5 nm, respectively. X-ray photoelectron spectroscopy (XPS) analysis showed the UCDs and HUCDs were mainly composed of carbon, oxygen and nitrogen. Fourier-transform infrared (FTIR) spectroscopy demonstrated the presence of functional groups, such as amino, hydroxyl, carboxylate and carbonyl groups onto the C-dots. The UCDs and HUCDs can be directly used for in vivo and in vitro imaging in Hela cells, Caenorhabditis elegans, onion epidermal cells and bean sprouts. The cytotoxicity study revealed that the UCDs and HUCDs were not toxic to normal rat kidney (NKR) cells with good biocompatibility. The results revealed that the C-dots derived from urine have good biocompatibility, strong fluorescence and may have potential to be a safe fluorescent probe for bio-imaging.

Cdk5 links with DNA damage response and cancer.

As an atypical member of cyclin dependent kinase family, Cyclin dependent kinase 5 (Cdk5) is considered as a neuron-specific kinase in the past decade due to the abundant existence of its activator p35 in post-mitotic neurons. Recent studies show that Cdk5 participates in a series of biological and pathological processes in non-neuronal cells, and is generally dysregulated in various cancer cells. The inhibition or knockdown of Cdk5 has been proven to play an anti-cancer role through various mechanisms, and can synergize the killing effect of chemotherapeutics. DNA damage response (DDR) is a series of regulatory events including DNA damage, cell-cycle arrest, regulation of DNA replication, and repair or bypass of DNA damage to ensure the maintenance of genomic stability and cell viability. Here we describe the regulatory mechanisms of Cdk5, its controversial roles in apoptosis and focus on its links to DDR and cancer.

microRNA-98 inhibits the proliferation, invasion, migration and promotes apoptosis of breast cancer cells by binding to HMGA2.

Breast cancer is a major contributor leading to cancer death in females worldwide. The aim of the present study was to investigate the effects of microRNA-98 (miR-98) on the processes of cell proliferation, invasion, migration and apoptosis by binding to high-mobility group AT-hook 2 (HMGA2) in breast cancer. Breast cancer tissues and adjacent normal tissues were collected from 112 patients suffering from breast cancer. The target relationship between miR-98 and HMGA2 was verified by in connection with the bioinformatics website as well as a dual-luciferase reporter assay, both of which provided evidence indicating that HMGA2 was a target gene of miR-98. Human breast cancer MDA-MB-231 cells were treated with miR-98 mimics, miR-98 inhibitors, siRNA-HMGA2 or miR-98 inhibitors + siRNA-HMGA2. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry methods were performed to determine cell proliferation, cell cycle and apoptosis, respectively, while a Transwell assay was employed to detect cell migration and invasion. Breast cancer tissues exhibited decreased miR-98 expression, while increased expression levels of HMGA2 were recorded. The mRNA and protein expressions of HMGA2, cell proliferation, cells at the S phase, cell migration, invasion, expressions of matrix metalloproteinase (MMP)2 as well as MMP9 were all reduced in response to miR-98 mimics or siRNA-HMGA2, while a contradictory trend was observed in the miR-98 inhibitors group. In conclusion, the results of the study demonstrate that miR-98 inhibits cell proliferation, migration and invasion, while acting to promote apoptosis by negatively regulating HMGA2 in breast cancer.

[Differences in light and heat utilization efficiency and yield of soybean in two ecological zones and their response to chemical control regulators]. / ä¸¤ä¸ªç”Ÿæ€åŒºå¤§è±†å ‰çƒ­èµ„æºåˆ©ç”¨çŽ‡å’Œäº§é‡çš„å·®å¼‚åŠå¯¹åŒ–æŽ§å‰‚çš„å“åº”.

The field experiment was conducted at two farms at Jiusan in Heihe (the fourth accumulated temperature zone) and at Lindian County of Daqing (the second accumulated temperature zone), both sites located in Heilongjiang Province, China. With soybean Kenfeng 41 as the test material, uniconazole (S3307, 50 mg·L-1) and 2-N, N- diethylamino ethyl caproate (DTA-6, 50 mg·L-1) were sprayed on leaves in the early flowering period of soybean. Through grey correlation analysis, the main factors affecting soybean yield were examined, and the differences of the light and heat utilization efficiency and soybean yield in two ecological conditions were compared. The regulation effects of chemical control technology on the light and heat utilization efficiency of soybean were explored. The results showed that the total surface radiation and ≥10 ℃ effective accumulated temperature were the main factors affecting soybean yield in both areas compared with rainfall and sunshine hours. The light and heat utilization efficiency from sowing to flowering period was significantly positively correlated with dry matter accumulation, and that from flowering to podding period was significantly positively correlated with dry matter accumulation per plant. There was a significant positive correlation between yield and dry matter accumulation, grain number per plant, grain mass per plant and 100-grain mass at seedling stage to podding stage. S3307 and DTA-6 could significantly improve light and heat utilization efficiency and soybean yield in both areas. S3307 showed the better regulation function to impact the light and heat utilization efficiency and yield than DTA-6 in both sites. In the two ecological areas of Jiusan and Lindian, spraying S3307 increased light utilization efficiency by 13.6% and 17.1%, and increased heat utilization efficiency by 14.1% and 17.2%, respectively. The yield by spraying S3307 was increased by 14.1% and 17.3% separately in Jiusan and Lindian. Therefore, it is the effective way to enhance resources utilization and achieve high-yield by using the reasonable chemical control technology.

Cell cycle protein Bora serves as a novel poor prognostic factor in multiple adenocarcinomas.

Cell cycle protein Bora has been identified to integrate the functions of three major mitotic kinases: Cyclin-dependent kinase-1, Polo-like kinase-1, and Aurora A kinase. Overexpression of Bora disrupts spindle assembly and causes genomic instability. However, the clinical relevance of Bora in cancer remains unclear. In this study, we examined the expression of Bora and its association with clinical characteristics in breast (n = 538), lung (n = 144) and gastric (n = 77) adenocarcinomas. We found that Bora was overexpressed in primary breast cancer tissues compared to paired non-cancerous tissues. Bora overexpression was observed at a higher proportion in triple-negative breast cancer (TNBC, 77.63%) compared with non-TNBC subtypes (42.76%, P < 0.0001). Kaplan-Meier survival analysis indicated that Bora overexpression was associated with unfavourable overall survival (OS, P < 0.0001) and disease-free survival (DFS, P = 0.007) in breast cancer. In addition, Bora subclassified patients with distinct clinical outcomes in both stages (II/III) and subtypes (HR+, HER2+) of breast cancer. Consistently, Bora was associated with adverse prognosis in lung (P = 0.005 for OS and DFS P = 0.001 for DFS) and gastric adenocarcinomas (P < 0.0001 for OS, and P < 0.0001 for DFS). Moreover, Bora was positively correlated with proliferation index Ki67 in breast and gastric cancer (P < 0.001, P = 0.005, respectively). Multivariate analyses further revealed that Bora was an independent prognostic parameter for OS and DFS in all three types of adenocarcinomas. In conclusion, our findings demonstrated that Bora was overexpressed and served as an independent biomarker for poor prognosis in multiple adenocarcinomas.

H19/let-7/LIN28 reciprocal negative regulatory circuit promotes breast cancer stem cell maintenance.

Long noncoding RNA-H19 (H19), an imprinted oncofetal gene, has a central role in carcinogenesis. Hitherto, the mechanism by which H19 regulates cancer stem cells, remains elusive. Here we show that breast cancer stem cells (BCSCs) express high levels of H19, and ectopic overexpression of H19 significantly promotes breast cancer cell clonogenicity, migration and mammosphere-forming ability. Conversely, silencing of H19 represses these BCSC properties. In concordance, knockdown of H19 markedly inhibits tumor growth and suppresses tumorigenesis in nude mice. Mechanistically, we found that H19 functions as a competing endogenous RNA to sponge miRNA let-7, leading to an increase in expression of a let-7 target, the core pluripotency factor LIN28, which is enriched in BCSC populations and breast patient samples. Intriguingly, this gain of LIN28 expression can also feedback to reverse the H19 loss-mediated suppression of BCSC properties. Our data also reveal that LIN28 blocks mature let-7 production and, thereby, de-represses H19 expression in breast cancer cells. Appropriately, H19 and LIN28 expression exhibits strong correlations in primary breast carcinomas. Collectively, these findings reveal that lncRNA H19, miRNA let-7 and transcriptional factor LIN28 form a double-negative feedback loop, which has a critical role in the maintenance of BCSCs. Consequently, disrupting this pathway provides a novel therapeutic strategy for breast cancer.

Morphine promotes cancer stem cell properties, contributing to chemoresistance in breast cancer.

Morphine is an opioid analgesic drug commonly used for pain relief in cancer patients. Here, we report that morphine enhances the mammosphere forming capacity and increases the expression of stemness-related transcription factors Oct4, Sox2 and Nanog. Treatment with morphine leads to enrichment of a side population fraction in MCF-7 cells and the CD44+/CD24(-/low) population in BT549 cells. Consistently, morphine activates Wnt/ß-catenin signaling to induce epithelial to mesenchymal transition and promotes metastasis. Moreover, morphine decreases the sensitivity of traditional anti-cancer drugs in breast cancer cells. Nalmefene, an antagonist of morphine, reverses morphine-induced cancer stem cell properties and chemoresistance in breast cancer. In addition, nalmefene abolishes morphine enhancing tumorigenesis in a NOD/SCID mouse model. In conclusion, our findings demonstrate that morphine contributes to chemoresistance via expanding the population of cancer stem cells and promotes tumor growth, thereby revealing a novel role of morphine and providing some new guides in clinical use of morphine.

Sulforaphane protects liver injury induced by intestinal ischemia reperfusion through Nrf2-ARE pathway.

AIM: To investigate the effect of sulforaphane (SFN) on regulation of NF-E2-related factor-2 (Nrf2)-antioxidant response element (ARE) pathway in liver injury induced by intestinal ischemia/reperfusion (I/R). METHODS: Rats were divided randomly into four experimental groups: control, SFN control, intestinal I/R and SFN pretreatment groups (n = 8 in each group). The intestinal I/R model was established by clamping the superior mesenteric artery for 1 h and 2 h reperfusion. In the SFN pretreatment group, surgery was performed as in the intestinal I/R group, with intraperitoneal administration of 3 mg/kg SFN 1 h before the operation. Intestine and liver histology was investigated. Serum levels of aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were measured. Liver tissue superoxide dismutase (SOD), myeloperoxidase (MPO), glutathione (GSH) and glutathione peroxidase (GSH-Px) activity were assayed. The liver transcription factor Nrf2 and heme oxygenase-1 (HO-1) were determined by immunohistochemical analysis and Western blotting analysis. RESULTS: Intestinal I/R induced intestinal and liver injury, characterized by histological changes as well as a significant increase in serum AST and ALT levels (AST: 260.13 +/- 40.17 U/L vs 186.00 +/- 24.21 U/L, P < 0.01; ALT: 139.63 +/- 11.35 U/L vs 48.38 +/- 10.73 U/L, P < 0.01), all of which were reduced by pretreatment with SFN, respectively (AST: 260.13 +/- 40.17 U/L vs 216.63 +/- 22.65 U/L, P < 0.05; ALT: 139.63 +/- 11.35 U/L vs 97.63 +/- 15.56 U/L, P < 0.01). The activity of SOD in the liver tissue decreased after intestinal I/R (P < 0.01), which was enhanced by SFN pretreatment (P < 0.05). In addition, compared with the control group, SFN markedly reduced liver tissue MPO activity (P < 0.05) and elevated liver tissue GSH and GSH-Px activity (P < 0.05, P < 0.05), which was in parallel with the increased level of liver Nrf2 and HO-1 expression. CONCLUSION: SFN pretreatment attenuates liver injury induced by intestinal I/R in rats, attributable to the antioxidant effect through Nrf2-ARE pathway.

[Histological study of livers from the patients with chronic hepatitis B treated with bicyclol].

OBJECTIVE: To study histological changes of the livers in patients with chronic viral hepatitis B treated with bicyclol tablets. METHODS: Thirty one patients with chronic viral hepatitis B were divided into two groups and were treated with bicyclol orally at doses of 150 mg daily or 75 mg daily for 36 weeds. The histological changes of the livers were observed before and after the treatment. RESULTS: Compared with pre-treatment findings, there were significant differences in histological activity index in each group (P < 0.01, P < 0.05), there were also significant differences between the two groups (P < 0.05). Decreased inflammatory reaction was also seen (P < 0.05). CONCLUSION: Daily use of 150 mg and 75 mg bicyclol tablets are effective in improving liver histological changes in chronic hepatitis B patients. Bicyclol 150 mg daily was better.