Cytochrome b561 regulates iron metabolism by activating the Akt/mTOR pathway to promote Breast Cancer Cells proliferation.

Breast cancer (BC) is the leading cause of cancer-related mortality in women, necessitating the development of novel therapeutic targets. While cytochrome b561 (CYB561) expression is associated with poor prognosis in BC, the precise role of CYB561 in BC and its potential mechanisms remain unclear. In the present study, we found that CYB561 plays an essential role in BC growth. CYB561 expression was up-regulated in surgically resected cancerous tissues and in six BC cell lines. Lentivirus-mediated CYB561 knockdown in BC cells significantly reduced their proliferation, migration, and invasiveness. CYB561 participates in the regulation of iron metabolism in BC. CYB561 knockdown reduced total iron content, increased ferrous iron content, and down-regulated the expression of proteins associated with iron metabolism (transferrin receptor 1, divalent metal transporter 1, and ferritin heavy chain 1). Conversely, up-regulation of CYB561 through co-incubation with exogenous iron (ferric ammonium citrate) produced contrary outcomes. Additionally, CYB561 activated the protein kinase B/mammalian target of rapamycin (Akt/mTOR) signaling pathway in BC cells. Down-regulation of CYB561 expression inhibited the Akt/mTOR signaling pathway activity. The application of an mTOR agonist (MHY1485) rescued this negative effect, as well as the inhibitory effect of CYB561 knockdown on cell proliferation. Importantly, the dual mTOR inhibitor MLN0128 (50 nM, 48 h) down-regulated CYB561 expression and the iron metabolism-related proteins transferrin receptor, divalent metal transporter 1, and ferritin heavy chain 1, whereas the mTOR agonist MHY1485 rescued the down-regulation of CYB561 knockdown on iron metabolism-related proteins. We conclude that CYB561 promotes the proliferation of BC cells by regulating iron metabolism through the activation of the Akt/mTOR signaling pathway.

Comprehensive Analysis of Subtypes and Identification of Key lncRNAs Based on Glutamine Metabolism-Related Long Noncoding RNAs.

Background: Long noncoding RNAs (lncRNAs) are becoming a critical class of metabolic regulate molecule in cancer. Glutamine is a regulator that contributes to each of the core metabolic tasks in proliferating tumor cells. Thus, we aimed to evaluate the association of lncRNAs with glutamine metabolism in lung adenocarcinoma (LUAD). Methods: Using single-sample gene set enrichment analysis (ssGSEA), LUAD specimens were assigned scores based on glutamine metabolism-related genes, and the shared common glutamine metabolism-related lncRNAs in three different LUAD data cohorts were identified. ConsensusClusterPlus was used to perform unsupervised clustering analysis in patients with LUAD. Key glutamine metabolism-related lncRNAs were identified by first-order partial correlation analysis. Results: A total of 11 shared glutamine metabolism-associated lncRNAs were identified in three LUAD data cohorts, and LUAD patients were classified into three glutamine metabolism subtypes based on the expressions of the related genes. C1 exhibited shorter overall survival (OS), poor genomic instability, and inadequate infiltration of immune cell types in the tumor microenvironment (TME) and was representative of the immunodeficiency phenotype. C2 represented the immunosuppressive phenotype while C3 represented the immune activation phenotype, exhibiting the highest sensitivity to immunotherapy. Nine of the 11 lncRNAs were localized to the nucleus. Finally, three key lncRNAs, significantly enriched in multiple metabolic pathways, were screened and found to be remarkably related to the OS of LUAD. Conclusion: We identified three glutamine metabolism subtypes of LUAD, which reflected different OS, genomic, and TME features, and identified three key glutamine metabolism-associated lncRNAs may contribute to further study of lncRNAs in cancer metabolism.

Role of CD4+T, CD8+T Cells, and CD4+T/CD8+T Cell Ratio in Gastric Cancer and Its Clinical Significance.

Objective: To study the expression and clinical importance of CD4+T, CD8+T cells, and CD4+T/CD8+T cell percentage in gastric cancer (GC) patients. Methods: The blood count of CD4+T and CD8+T lymphocytes was ascertained via flow cytometry before surgery in 93 GC patients undergoing gastrectomy. The CD4+T, CD8+T, and Foxp3+T lymphocytes in cancerous and normal adjacent tissues and the presence of PD-L1 in cancerous tissues were detected via immunohistochemistry. The link between the permeation of CD4+T, CD8+T lymphocytes in venous blood, and cancer and normal adjacent tissues was analyzed. Results: Lauren histotype, TNM stage, lymphatic/nervous invasion, and NLR level were all considerably associated with peripheral CD4+T and CD8+T cell levels, whereas CD8+T lymphocytes were also associated with vascular invasion (p < 0.05). The CD4+T lymphocyte counts, CD4+T, and CD8+T cell percentage in GC tissues were found to have been decreased when compared to normal adjacent tissues, whereas the CD8+T and Foxp3+T lymphocyte count was higher in GC tissues (p < 0.05). According to a Spearman analysis, the CD4+T and CD8+T cell counts in tumor tissues were positively related to the Foxp3+T lymphocyte count (p < 0.05). Greater peripheral CD4+T lymphocyte counts and increased level of CD4+T/CD8+T percentage corresponded with greater CD4+T cell levels and increased CD4+T/CD8+T quantity in normal adjacent tissues. Higher levels of peripheral CD8+T cells corresponded with higher quantities of CD8+T cells in cancer tissues. A reduced CD4+T lymphocyte count, together with a reduced CD4+T/CD8+T percentage in venous blood, was consistent with a diminished CD4+T cell count along with a reduced CD4+T/CD8+T lymphocyte ratio in cancer and normal adjacent tissues. Conclusion: The peripheral quantity of CD4+T and CD8+T lymphocytes in GC patients can partly reflect the infiltrating state of these lymphocytes in cancer and normal adjacent tissues and can preliminarily predict immunotherapy response to a certain extent.

Expression and clinical prognostic value of CYB561 in breast cancer.

PURPOSE: The expression of cytochrome B561 (CYB561) and its role in breast cancer (BC) prognosis remain unclear. We analyzed the differential expression and prognostic value of CYB561 using online databases and a clinical cohort through bioinformatics and immunohistochemistry. METHODS: The differential expression of CYB561 and its association with BC were analyzed using the tumor immune estimation resource (TIMER), gene expression profiling interaction analysis2 (GEPIA2), Human Protein Atlas, Cancer Cell Line Encyclopedia, and Kaplan-Meier Plotter website. Important pathways of CYB561 enrichment were explored using gene set enrichment analysis. Immunohistochemistry detected CYB561 expression in normal breast, breast hyperplasia, ductal carcinoma in situ (DCIS), para-cancer, and invasive BC groups. Association between CYB561 expression and BC prognosis was analyzed using Kaplan-Meier and Cox regression analyses. RESULTS: CYB561 mRNA expression was higher in GEPIA and TIMER BC patients than in para-cancer tissues. CYB561 was expressed in the glandular epithelium and myoepithelium, with positive localization in the cytoplasm and cell membrane. CYB561 protein expression significantly differed among the groups. CYB561 expression was correlated with ERBB2/HER2 and infiltrating CD4+ T cells in GEPIA and TIMER BC patients and associated with HER2 status, histological grade, and molecular subtypes in the clinical cohort but not related to tumor-infiltrating lymphocytes. CYB561 mRNA overexpression predicted reduced recurrence-free survival and overall survival in BC. Patients with CYB561 expression had significantly reduced overall survival and increased risk of death. CONCLUSION: CYB561 can serve as an effective clinical prognostic biomarker for BC.

Luminescent monomeric and dimeric Ru(ii) acyclic carbene complexes as selective sensors for NH3/amine vapor and humidity.

A new class of luminescent bis(bipyridyl) Ru(ii) pyridyl acyclic carbene complexes with environmentally-sensitive dimerization equilibrium have been developed. Owing to the involvement of the orbitals of the diaminocarbene ligand in the emissive excited state, the phosphorescence properties of these complexes are strongly affected by H-bonding interactions with various H-bonding donor/acceptor molecules. With the remarkable differences in the emission properties of the monomer, dimer, and H-bonded amine adducts together with the change of the dimerization equilibrium, these complexes can be used as luminescent gas sensors for humidity, ammonia, and amine vapors. With the responses to amines and humidity and the corresponding change in the luminescence properties, a proof-of-principle for binary optical data storage with a reversible concealment process has been described.

Analysis of the Curative Effect of Posterior Approach on Lumbar Brucellar Spondylitis with Abscess through Magnetic Resonance Imaging under Improved Watershed Algorithm.

To explore the performance of improved watershed algorithm in processing magnetic resonance imaging (MRI) images and the effect of the processed images on the treatment of lumbar brucellar spondylitis (BS) with abscess by the posterior approach, the watershed algorithm was improved by adding constraints such as noise reduction and regional area attribute. 50 patients with abscessed lumbar disc herniation admitted to the hospital from January 2018 to January 2019 were selected, and all of them were examined by MRI. They were rolled into two groups in random. The treatment group (n = 25) accepted surgery with the aid of MRI images processed by the improved watershed algorithm, and the control group (Ctrl group) (n = 25) accepted surgery with the aid of unprocessed MRI images. The improved watershed algorithm can accurately segment the spine, and the segmentation results were relatively excellent. In contrast with the unprocessed MRI image, that processed by the improved watershed algorithm had a positive effect on the operation. In contrast with the Ctrl group, the visual analogue scale pain score (VAS), oxygen desaturation index (ODI), erythrocyte sedimentation rate (ESR), and high sensitivity C-reactive protein (CRP) were obviously lower (p < 0.05). The improved watershed algorithm proposed performs better in MRI image processing and can effectively enhance the resolution of MRI images. At the same time, the posterior approach has a good effect in the treatment of lumbar BS with abscess and is worthy of clinical promotion.

D-A type sensor array for differentiation and identification of white wine varieties based on specific solvent effect activated by CT-LE transition.

In this work, we synthesize a series of compounds with electron donor (D) and acceptor (A) units. They show general solvent effect in aprotic solvents, suggesting a charge transfer (CT) process. While in protic solvents including water, ethanol and methanol, the spectra exert no polarity-dependence but a remarkable hypochromatic shift together with the fading of CT band. Dynamic analysis implies that intermolecular hydrogen bond will be formed between carboxylic acid and protic solvent, boosting another deactivation pathway that jumps off a bigger energy gap, in other words, favoring the locally excited (LE) state emission. The CT-LE transition involves variations in both absorption and emission spectra, and further poses competition with other mechanisms including activated/restricted intramolecular rotation (IR/RIR). Inspired by the cross-reactivity, we turn our attention to the development of sensor array, in order to identify white wine varieties. The differential spectral responses are recorded, generating multiple factors including absorption wavelength (λab), emission wavelength (λem), absorbance (Abs.) and emission intensity (Int.). These factors are processed with principal component analysis (PCA), creating a three-dimensional fingerprint data base for white wines. The data points in the coordinate system are clustered into 10 different groups, demonstrating a clear differentiation of all the white wines. More importantly, as our final test for whether the sensor array can identify the counterfeits, an adulterated liquor sample, which is provided by police officers, is fingerprinted on the three-dimensional diagram. Its canonical factors fall into an area distinct from the adulterated wine, indicating a clear identification.

A turn-on type stimuli-responsive fluorescent dye with specific solvent effect: Implication for a new prototype of paper using water as the ink.

In this study, we reported the photoluminescence (PL) behaviour of a new intramolecular charge transfer (ICT) compound, ((E)-2-(((2-hydroxynaphthalen-1-yl)methylene)amino)benzoic acid, (HABA), which shows ICT solvent effect in aprotic solvents as confirmed by absorption and emission spectra. While in protic solvents including water and ethanol, the charge transfer (CT) band significantly reduces. Remarkable fluorescence enhancement in the blue region was also observed for HABA in polar protic solvents. We described such phenomena as "specific solvent effect". It can be ascribed to the hydrogen bonding formation between HABA and protic solvents, which not only causes significant reduction in the rate of internal conversion but also elevates the energy gap. Density functional theory (DFT) calculations as well as the dynamics analysis were performed to further verify the existence of hydrogen bonding complexes. Stronger emission turn-on effect was observed on HABA solid film when it is treated with water and base solution. The stimuli-responsive fluorescence of HABA enables a new green printing technique that uses water/base as the ink, affording fluorescent handwritings highly distinct from the background. Thermoanalysis of the dye suggests the nice thermostability, which is highly desired for real-world printing in a wide temperature range.

[Fluorescence Properties and the Detection of Benzaldehyde of Lanthanide Complex with 2-Sufoterephthalalic Acid].

A new lanthanide coordination polymer, [Eu(2-stp) (2,2'-bipy) (H2O)] · H2O (2-stp = 2-sufoterephthalalic acid, 2, 2'-bipy=2,2'-bipyridine) was obtained by hydrothermal method. The crystal structure was determined by single crystal X-ray diffraction. The complex has a one-dimensional parallel double-chain structure. Eu³âº is a nine-coordinated by six O atoms from three 2-sufoterephthalalic acids, one water molecule and two N atoms from 2,2'-bipyridine. The fluorescence properties of the complex were studied. The complex shows the characteristics narrow emission of ion at 581, 594, 619, 654 and 698 nm, corresponding to 5D0-->Fj (J = 0-4) transitions. The strongest emission peak is at 619 nm, corresponding to 5D0-F2 transition for red light. Different organic solvents have different effects on the fluorescence intensity of the complex, and enzaldehyde exerts the most significant fluorescence quenching effect. So, this complex can be used as a fluorescent sensing probe for benzaldehyde.

Excision repair cross-complementation group 1 codon 118 polymorphism, micro ribonucleic acid and protein expression, clinical outcome of the advanced gastric cancer response to first-line FOLFOX-4 in Qinghai-Tibetan plateau population.

CONTEXT: The excision repair cross-complementation group 1 (ERCC1) codon 118 C/T polymorphism has been associated with clinical outcome in cancer patients treated with platinum chemotherapy. Ethnic differences in the frequency of this polymorphism have been observed in Caucasian and African populations. AIM: The aim of this study was to evaluate the frequency and survival benefit of the ERCC1 codon 118 C/T polymorphism in a high-altitude population with advanced gastric cancer. MATERIALS AND METHODS: Polymerase chain reaction-restriction fragment length polymorphism was used to determine the frequency of ERCC1 118 codon C/T polymorphism in 206 advanced gastric cancer patients residing in the high-altitude Qinghai-Tibetan plateau. The influence of the ERCC1 codon 118 C/T polymorphism on its micro ribonucleic acid (mRNA) and protein expression, clinicopathological features; response to the platinum-based combination chemotherapy, and the outcome was evaluated. STATISTICAL ANALYSIS: The Kaplan-Meier method was used for survival analysis. The correlation of ERCC1 codon 118 polymorphism with ERCC1 mRNA and protein expression, clinicopathological characteristics, and first-line oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX-4) response was determined by χ(2)-test. RESULTS AND CONCLUSIONS: ERCC1 codon 118 C/T polymorphism was not associated with ERCC1 mRNA and protein expression, FOLFOX-4 response, and progression-free survival (PFS) or overall survival (OS). High ERCC1 mRNA and protein expression levels were associated with significantly lower FOLFOX-4 responses, PFS, and OS. ERCC1 codon 118 C/T polymorphism is not an important prognostic marker for advanced gastric cancer. Determination of ERCC1 mRNA and protein levels may be beneficial in predicting the response and outcome of FOLFOX-4 therapy in gastric cancer.