Identification of CHRNB4 as a Diagnostic/Prognostic Indicator and Therapeutic Target in Human Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignant tumors and there is a lack of biomarkers for ESCC diagnosis and prognosis. Family subunits of cholinergic nicotinic receptor genes (CHRNs) are involved in smoking behavior and tumor cell proliferation. Previous researches have shown similar molecular features and pathogenic mechanisms among ESCC, head and neck squamous cell carcinoma (HNSC), and lung squamous cell carcinoma (LUSC). Using edgeR, three mutual differentially expressed genes of CHRNs were found to be significantly upregulated at the mRNA level in ESCC, LUSC, and HNSC compared to matched normal tissues. Kaplan-Meier survival analysis showed that high expression of CHRNB4 was associated with unfavorable prognosis in ESCC and HNSC. The specific expression analysis revealed that CHRNB4 is highly expressed selectively in squamous cell carcinomas compared to adenocarcinoma. Cox proportional hazards regression analysis was performed to find that just the single gene CHRNB4 has enough independent prognostic ability, with the area under curve surpassing the tumor-node-metastasis (TNM) staging-based model, the most commonly used model in clinical application in ESCC. In addition, an effective prognostic nomogram was established combining the TNM stage, gender of patients, and expression of CHRNB4 for ESCC patients, revealing an excellent prognostic ability when compared to the model of CHRNB4 alone or TNM. Gene Set Enrichment Analysis results suggested that the expression of CHRNB4 was associated with cancer-related pathways, such as the mTOR pathway. Cell Counting Kit-8, cloning formation assay, and western blot proved that CHRNB4 knockdown can inhibit the proliferation of ESCC cells via the Akt/mTOR and ERK1/2/mTOR pathways, which might facilitate the prolonged survival of patients. Furthermore, we conducted structure-based molecular docking, and potential modulators against CHRNB4 were screened from FDA approved drugs. These findings suggested that CHRNB4 specifically expressed in SCCs, and may serve as a promising biomarker for diagnosis and prognosis prediction, and it can even become a therapeutic target of ESCC patients.

The Synthesis and Biological Function of a Novel Sandwich-Type Complex Based on {SbW9 } and Flexible bpp Ligand.

A novel sandwich-type complex [Na(H2 O)4 ][{Na3 (H2 O)5 }{Mn3 (bpp)3 } (SbW9 O33 )2 }]·8H3 O (MnSbW-bpp) (bpp = 1,3-bis(4-pyridyl) propane) is synthesized and characterized by elemental analysis, IR, thermogravimetric analysis, and single-crystal X-ray diffraction. The MnSbW-bpp compound is the first sandwich case bridged by a flexible ligand. Its biological function of MnSbW-bpp in antitumor activity is also determined in vitro and in vivo. The inhibitory proliferation and induction of apoptosis are performed by flow cytometry assay, S180 (sarcoma) tumor xenograft in ICR mice, the color Doppler ultrasound monitor, and TdT-mediated dUTP-biotin nick end labeling assay. The results show that the novel compound-MnSbW-bpp-is synthesized and identified by its physical and chemical characteristics, such as the fluorescent and paramagnetic activities. MnSbW-bpp indicates a potency inhibition of human cancer lines, such as SGC-7901, HT-29, HepG2, Hela, U2OS, SaoS2, and HMC cells. MnSbW-bpp also inhibits the growth of tumor xenograft in mice, induced cell apoptosis, and released cytochrome c in vivo and in vitro. Thus, MnSbW-bpp, as a new compound, possesses the potent inhibition of cancer cells, which indicates that the MnSbW-bpp has potential merit for the further evaluation of a novel antitumor agent.

Prognostic genes of breast cancer revealed by gene co-expression network analysis.

The aim of the present study was to identify genes that may serve as markers for breast cancer prognosis by constructing a gene co-expression network and mining modules associated with survival. Two gene expression datasets of breast cancer were downloaded from ArrayExpress and genes from these datasets with a coefficient of variation >0.5 were selected and underwent functional enrichment analysis with the Database for Annotation, Visualization and Integration Discovery. Gene co-expression networks were constructed with the WGCNA package in R. Modules were identified from the network via cluster analysis. Cox regression was conducted to analyze survival rates. A total of 2,669 genes were selected, and functional enrichment analysis of them revealed that they were mainly associated with the immune response, cell proliferation, cell differentiation and cell adhesion. Seven modules were identified from the gene co-expression network, one of which was found to be significantly associated with patient survival time. Expression status of 144 genes from this module was used to cluster patient samples into two groups, with a significant difference in survival time revealed between these groups. These genes were involved in the cell cycle and tumor protein p53 signaling pathway. The top 10 hub genes were identified in the module. The findings of the present study could advance the understanding of the molecular pathogenesis of breast cancer.

IMM-H007, a new therapeutic candidate for nonalcoholic fatty liver disease, improves hepatic steatosis in hamsters fed a high-fat diet.

Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease in humans, is characterized by the accumulation of triacylglycerols (TGs) in hepatocytes. We tested whether 2',3',5'-tri-acetyl-N6-(3-hydroxylaniline) adenosine (IMM-H007) can eliminate hepatic steatosis in hamsters fed a high-fat diet (HFD), as a model of NAFLD. Compared with HFD-only controls, IMM-H007 treatment significantly lowered serum levels of TG, total cholesterol, and free fatty acids (FFAs) in hamsters fed the HFD, with a prominent decrease in levels of serum transaminases and fasting insulin, without affecting fasting glucose levels. Moreover, 1H-MRI and histopathological analyses revealed that hepatic lipid accumulation and fibrosis were improved by IMM-H007 treatment. These changes were accompanied by improvement of insulin resistance and oxidative stress, and attenuation of inflammation. IMM-H007 reduced expression of proteins involved in uptake of hepatic fatty acids and lipogenesis, and increased very low density lipoprotein secretion and expression of proteins responsible for fatty acid oxidation and autophagy. In studies in vivo, IMM-H007 inhibited fatty acid import into hepatocytes and liver lipogenesis, and concomitantly stimulated fatty acid oxidation, autophagy, and export of hepatic lipids. These data suggest that IMM-H007 resolves hepatic steatosis in HFD-fed hamsters by the regulation of lipid metabolism. Thus, IMM-H007 has therapeutic potential for NAFLD.

In situ grown, self-supported iron-cobalt-nickel alloy amorphous oxide nanosheets with low overpotential toward water oxidation.

Electrocatalytic water oxidation by in situ grown iron-cobalt-nickel ternary alloy amorphous oxides is reported. This catalytic material was prepared by simple anodization of an alloy plate followed by low-temperature annealing, which shows superior electrocatalytic activity toward oxygen evolution reaction with an overpotential of only 170 mV and a low Tafel slope.

A simple and label-free aptasensor based on nickel hexacyanoferrate nanoparticles as signal probe for highly sensitive detection of 17ß-estradiol.

A simple and label-free electrochemical aptasensor was developed for detecting 17ß-estradiol (E2). To translate the binding events between aptamer and E2 into the measurable electrochemical signal, the nickel hexacyanoferrate nanoparticles (NiHCF NPs) as signal probe was in situ introduced on the electrode by a simple two-step deposition method, exhibiting well-defined peaks with good stability and reproducibility. Subsequently, Au nanoparticles (Au NPs) was covered on the NiHCF NPs, which not only provided a platform for immobilizing the aptamer by S-Au interaction, but further enhanced the conductivity and stability of the signal probe. With the addition of E2, the formation of E2-aptamer complexes on the sensing interface retarded the interfacial electron transfer reaction of the probe, resulting in the decrease of the electrochemical signal. E2 could be readily examined by measuring the signal change. A linear range of 1×10(-12)-6×10(-10) M was obtained with a low detection limit of 0.8×10(-12) M. The aptasensor also exhibited high specificity to E2 in control experiments employing seven endocrine disrupting compounds as the interferents that had similar structure or coexisted with E2 in the environment. Besides, the applicability of the aptasensor was successfully evaluated by determining E2 in the real samples.

A femtomolar level and highly selective 17ß-estradiol photoelectrochemical aptasensor applied in environmental water samples analysis.

Driven by the urgent demand of determining low level of 17ß-estradiol (E2) present in environment, a novel and ultrasensitive photoelectrochemical (PEC) sensing platform based on anti-E2 aptamer as the biorecognition element was developed onto CdSe nanoparticles-modified TiO2 nanotube arrays. The designed PEC aptasensor exhibits excellent performances in determination of E2 with a wide linear range of 0.05-15 pM. The detection limit of 33 fM is lower than the previous reports. The aptasensor manifests outstanding selectivity to E2 while used to detect seven other endocrine disrupting compounds that have similar structure or coexist with E2. The superior sensing behavior toward E2 can be attributed to the appropriate PEC sensing interface resulting from the preponderant tubular microstructure and excellent photoelectrical activity, the large packing density of aptamer on the sensing interface, as well as the high affinity of the aptamer to E2. The PEC aptasensor was applied successfully to determine E2 in environmental water samples without complicate sample pretreatments, and the analytical results showed good agreement with that determined by HPLC. Thus, a simple and rapid PEC technique for detection low level of E2 was established, having promising potential in monitoring environmental water pollution.

Fabrication of a novel and simple microcystin-LR photoelectrochemical sensor with high sensitivity and selectivity.

Microcystin-LR (MC-LR), an inert electrochemical species, is difficult to be detected by a simple and direct electrochemical method. In the present work, a novel photoelectrochemical sensor is developed on highly ordered and vertically aligned TiO(2) nanotubes (TiO(2) NTs) with convenient surface modification of molecularly imprinted polymer (MIP) (denoted as MIP@TiO(2) NTs) for highly sensitive and selective determination of MC-LR in solutions. Molecularly imprinted polypyrrole (PPy) of MC-LR is chosen as the recognition element. The designed MIP@TiO(2) NTs photoelectrochemical sensor presents excellent applicability in MC-LR determination, with linear range from 0.5 to 100 µg L(-1) and limit of detection of 0.1 µg L(-1). Moreover, the sensor exhibits outstanding selectivity while used in coexisting systems containing 2,4-dichorophenoxyacetic acid, atrazine, paraquat, or monosultap with high concentration, 100 times that of MC-LR. The sensor presents good photoelectric conversion efficiency and detection sensitivity, as well as broad linear detection range, mainly because of the high specific surface area and photoelectric activity of TiO(2) NTs and the π bond delocalized electron system of PPy that promotes the separation of electron-holes. The prominent selectivity is from the MIP by forming multiple hydrogen bonds between PPy and MC-LR. Mechanisms for photoelectrochemical analysis and selective recognition are also discussed.