Cell Division Cycle Associated 8 Is a Key Regulator of Tamoxifen Resistance in Breast Cancer.

PURPOSE: Breast cancer (BC) is one of the most common malignancies globally, and millions of women worldwide are diagnosed with BC every year. Up to 70% of BC patients are estrogen receptor (ER)-positive. Numerous studies have shown that tamoxifen has a significant therapeutic effect on both primary and metastatic ER-positive BC patients. Although tamoxifen is currently one of the most successful therapeutic agents for BC, a significant proportion of patients will eventually become resistant to tamoxifen, leading to tumor recurrence and metastasis. Knowledge about the development of tamoxifen resistance in BC patients is still limited. METHODS: We applied a loss-and-gain method to study the biological functional role of cell division cycle associated 8 (CDCA8) in tamoxifen resistance in BC cells. RESULTS: We found that CDCA8 was significantly elevated in tamoxifen-resistant BC cells. Knockdown of CDCA8 expression significantly inhibited the proliferation of tamoxifen-resistant BC cells and reduced their resistance to tamoxifen. In contrast, overexpression of CDCA8 promoted the growth of tamoxifen-sensitive BC cells and induced their resistance to tamoxifen. CONCLUSION: In this study, we reported that CDCA8 is a key regulator of tamoxifen resistance in BC, suggesting that CDCA8 may serve as a potential therapeutic target for BC treatment.

CDCA8 is a key mediator of estrogen-stimulated cell proliferation in breast cancer cells.

Endocrine therapy is effective in the early stage of breast cancer treatment, and most tumor cells will gain the ability to proliferate under residual amounts of estrogen, which will cause the recurrence of the disease. The role of cell division cycle associated 8 (CDCA8) in Estradiol (E2)-stimulated breast cancer cells growth is investigated in this research. CDCA8 showed higher mRNA expression in E2-stimulated MCF7 and T47D cells, and such an increase could also be observed in tumor samples. CDCA8 shRNA inhibited the survival and growth detected by cell number and colony formation, while promoted cell cycle G1 phase arrest determined with flow cytometry, which coordinated with a decrease in E2-induced molecules, namely Cyclin D1 (CCND1), B-Cell CLL/Lymphoma 2 (BCL2), and an increase in apoptosis-related molecules, such as cyclin-dependent kinase inhibitor 1a (P21) and cyclin-dependent kinase inhibitor 1b (P27). Kaplan-Meier plot analysis indicated that higher CDCA8 expression was positively associated with poor prognosis with a probability lower than 0.4 at the five-year interval (p = 0.035). All of these suggest that CDCA8 is a key mediator of estrogen-stimulated breast cancer cell growth and survival, which can be utilized as a novel target in breast cancer treatment.

3D graphene-based foam induced by phytic acid: An effective enzyme-mimic catalyst for electrochemical detection of cell-released superoxide anion.

Here we present a new method to fabricate enzyme-mimic metal-free catalysts for electrochemical detection of superoxide anion (O2•-) by introducing phosphate groups into graphene-based foam. Through a template-free hydrothermal process, graphene oxide (GO) was treated with different amount of phytic acid (PA) to obtain 3D porous graphene-based foam (PAGF). Characterizations demonstrate that phosphate groups were successfully modified on the surface and inter layer structure of PAGF materials and the defects and disorder degree of PAGF could be controlled by adjusting the addition of PA precursors. Meanwhile, the synthesized PAGF was successfully immobilized on screen printed carbon electrodes (SPCEs) and employed in O2•- detection. With PA treated on graphene structure, the resulted PAGF/SPCEs exhibit distinct characteristic redox peaks, showing enzyme-mimic catalytic activity toward O2•- dismutation. Also, the amount of modified phosphate groups has caused a considerable variety on the performance of PAGF-based electrodes. Apart from high sensitivity, wide liner range, low detection limit, good selectivity and long-term stability, our sensors also present satisfying performance in the real-time monitoring of drug-induced O2•- released from Hela cells. The reliability of the biological measurement was further demonstrated via electron paramagnetic resonance (EPR) to characterize the released O2•- from stimulated cells by using 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) to trap the transient O2•-. The above results indicate that our established sensors hold potential application in the real-time detection of O2•- in biological samples.

A facile way to fabricate manganese phosphate self-assembled carbon networks as efficient electrochemical catalysts for real-time monitoring of superoxide anions released from HepG2 cells.

Quantification of superoxide anions (O2•-) is significant in the monitoring of many serious diseases and the design of enzyme-mimic catalysts plays the main role in the development of non-enzymatic O2•- sensors. Herein, we proposed a facile self-assembly process to synthesize manganese phosphate modified carbon networks using three kinds of widely-used carbon materials (MWCNTs, NGS and GO) as pillar connectors. Characterizations demonstrate that manganese phosphate is widely dispersed inside and on the surface of carbon networks without visible morphology. Meanwhile, all three kinds of synthesized catalysts were successfully immobilized on the screen-printed carbon electrodes to evaluate the electrochemical performance of fabricated sensors. The results indicate that sensors based on Mnx(PO4)y modified MWCNTs exhibit high sensitivity with an extremely low detection limit of 0.127µM (S/N = 3) and a wide liner range of 0-1.817mM (R2 = 0.998). We further employed the recommended sensors in the real-time monitoring of HepG2 cells released O2•- under the stimulating of Zymosan (20mg/mL). Noticeably, the proposed sensors exhibit not only sensitive response but also stable current steps upon different addition of Zymosan. The calculated concentrations of cell-released O2•- vary from 6.772 to 24.652pM cell-1 for the Zymosan amount used in this work. The established novel sensors display low background current and signal noises, thus holding unique advantages in the trace analysis of O2•- in biological samples and in vivo environment.

Uncapped nanobranch-based CuS clews used as an efficient peroxidase mimic enable the visual detection of hydrogen peroxide and glucose with fast response.

Nanosized materials acting as substitutes of natural enzymes are currently attracting significant research due to their stable enzyme-like characteristics, but some flaws of these nanozymes, including their limited catalytic rate and efficiency, need to be remedied to enable their wider applications. In this work, we verify for the first time the catalytic behavior of uncapped nanobranch-based CuS clews as a peroxidase mimic. XRD, XPS, SEM, and TEM proofs demonstrate that high-purity CuS clews composed of intertwined wires with abundant nanodendrites outside are successfully produced via a facile one-pot hydrothermal synthesis approach, with thiourea as both the sulfion source and the structure-directing agent. The synthesized CuS can catalytically oxidize 3,3',5,5'-tetramethylbenzidine (TMB) by H2O2 to trigger a visible color reaction with rapid response (reaching a maximum change within 5 min). The proposed CuS nanozyme exhibits preferable catalytic kinetics over natural horseradish peroxidase (HRP). This outstanding activity primarily results from the large surface area and rich sites exposed by the uncapped unique structure. Under optimized conditions, the fabricated sensing system provides linear absorbance (652 nm) changes in the H2O2 concentration range of 0.2˜130 µM, with a detection limit of as low as 63 nM. When coupled with glucose oxidase (GOD), the system is demonstrated to be capable of monitoring glucose in blood samples with excellent performance.

Anneal-shrinked Cu2O dendrites grown on porous Cu foam as a robust interface for high-performance nonenzymatic glucose sensing.

Enzyme-free electrochemical detection of glucose in alkaline media with favorable properties has been acquired by fabricating a robust and large-surface sensing platform, which is composed of anneal-shrinked Cu2O dendrites grown on porous Cu foam. On the one hand, the good compatibility of electrodeposited Cu2O architectures and Cu foam substrate, together with a post-deposition anneal at 200°C, offers a mechanically stable interface for glucose determination. On the other hand, the macropores of Cu foam that is decorated with unique Cu2O dendrites provide large active surface for electrocatalytic reaction and mass transport. As a result, selective sensing of glucose in the linear concentration range of 0.001-1.4mM was achieved on the fabricated sensor, with a sensitivity of as high as 5.04mAcm-2mM-1 and a detection limit of 0.13µM. Desired long-term performance stability was obtained, partially due to the strong adhesion of Cu2O microstructures to the Cu foam support after annealing. Practical monitoring of glucose in serum samples was also demonstrated on the proposed sensor.

Ultrasensitive detection of superoxide anion released from living cells using a porous Pt-Pd decorated enzymatic sensor.

Considering the critical roles of superoxide anion (O2(∙-)) in pathological conditions, it is of great urgency to establish a reliable and durable approach for real-time determination of O2(∙-). In this study, we propose a porous Pt-Pd decorated superoxide dismutase (SOD) sensor for qualitative and quantitative detection O2(∙-). The developed biosensor exhibits a fast, selective and linear amperometric response upon O2(∙-) in the concentration scope of 16 to 1,536 µM (R(2)=0.9941), with a detection limit of 0.13 µM (S/N=3) and a low Michaelis-Menten constant of 1.37 µM which indicating a high enzymatic activity and affinity to O2(∙-). Inspiringly, the proposed sensor possesses an ultrahigh sensitivity of 1270 µA mM(-1)cm(-2). In addition, SOD/porous Pt-Pd sensor exhibits excellent anti-interference property, reproducibility and long-term storage stability. Beyond our expectation, the trace level of O2(∙-) released from living cells has also been successfully captured. These satisfactory results are mainly ascribed to (1) the porous interface with larger surface area and more active sites to provide a biocompatible environment for SOD (2) the specific biocatalysis of SOD towards O2(∙-) and (3) porous Pt-Pd nanomaterials fastening the electron transfer. The superior electrochemical performance makes SOD/porous Pt-Pd sensor a promising candidate for monitoring the dynamic changes of O2(∙-)in vivo.

Lenses axial space ray tracing measurement.

In order to achieve the precise measurement of the lenses axial space, a new lenses axial space ray tracing measurement (ASRTM) is proposed based on the geometrical theory of optical image. For an assembled lenses with the given radius of curvature r(n) and refractive index nn of every lens, ASRTM uses the annular laser differential confocal chromatography focusing technique (ADCFT) to achieve the precise focusing at the vertex position P(n) of its inner-and-outer spherical surface Sn and obtain the coordinate z(n) corresponding to the axial movement position of ASRTM objective, and then, uses the ray tracing facet iterative algorithm to precisely determine the vertex position P(n) of every spherical surface by these coordinates z(n), refractive index n(n) and spherical radius r(n), and thereby obtaining the lenses inner axial space d(n). The preliminary experimental results indicate that ASRTM has a relative measurement error of less than 0.02%.