Butylated hydroxyanisole induces distinct expression patterns of Nrf2 and detoxification enzymes in the liver and small intestine of C57BL/6 mice.

Butylated hydroxyanisole (BHA) is widely used as an antioxidant and preservative in food, food packaging and medicines. Its chemopreventive properties are attributing to its ability to activate the transcription factor NF-E2 p45-related factor 2 (Nrf2), which directs central genetic programs of detoxification and protection against oxidative stress. This study was to investigate the histological changes of Nrf2 and its regulated phase II enzymes Nqo1, AKR1B8, and Ho-1 in wild-type (WT) and Nrf2(-/-) mice induced by BHA. The mice were given a 200mg/kg oral dose of BHA daily for three days. Immunohistochemistry revealed that, in the liver from WT mice, BHA increased Nqo1 staining in hepatocytes, predominately in the pericentral region. In contrast, the induction of AKR1B8 appeared mostly in hepatocytes in the periportal region. The basal and inducible Ho-1 was located almost exclusively in Kupffer cells. In the small intestine from WT mice, the inducible expression patterns of Nqo1 and AKR1B8 were nearly identical to that of Nrf2, with more intense staining in the villus than that the crypt. Conversely, Keap1 was more highly expressed in the crypt, where the proliferative cells reside. Our study demonstrates that BHA elicited differential expression patterns of phase II-detoxifying enzymes in the liver and small intestine from WT but not Nrf2(-/-) mice, demonstrating a cell type specific response to BHA in vivo.

A bibliometric and visualization analysis of research trends and hotspots on targeted therapy for breast cancer from 2003 to 2022.

Background: Breast cancer is a significant public health issue, exhibiting the most pronounced occurrence and fatality rates among malignant neoplasms globally. Targeted therapy is a medical intervention that focuses on specific molecular markers. This study aims to investigate and evaluate the current research trends and directions in the field of targeted therapy for breast cancer using bibliometric analysis. Method: The Web of Science database was utilized to retrieve relevant articles published between 2003 and 2022. The VOSviewer software and Bibliometrix package in the R language were employed to conduct co-occurrence and clustering analyses of authors, countries, institutions, journals, references, and the CiteSpace tool was utilized for keyword burst detection. Results: A total of 2,258 articles were included and the annual number of publications increased rapidly. The most prolific country on this topic was the USA (n=898, 39.77%) and the University of Texas MD Anderson Cancer Center published most papers (n=93). Dennis J. Slamon and Gabriel N. Hortobagyi stood out in the field, with Dennis J. Slamon leading in terms of co-citations(n=653) and Gabriel N. Hortobagyi topping the list in terms of published articles(n=18). The most productive journal was Breast Cancer Research and Treatment and the most cited journal was Journal of Clinical Oncology. The clustering of keywords indicated that the primary focus of researches in the past two decades was on the development and clinical evaluation of tumor-targeted drugs associated with the epidermal growth factor receptor (EGFR) family signaling pathway, and explored mechanisms related to biological behavior of breast cancer. Keywords co-occurrence and burst analysis identified current research hotspots and potential research trends. Conclusion: This study employed bibliometric analysis to examine research on targeted therapy for breast cancer over a span of 20 years, and identified development trends of research and elucidated potential research trajectories in the domain of this topic. This study helps in the identification of prospective collaborators and partner institutions for researchers.

Achieve High Dielectric and Energy-Storage Density Properties by Employing Cyanoethyl Cellulose as Fillers in PVDF-Based Polymer Composites.

Fluoropolymer/inorganic nanofiller composites are considered to be ideal polymer dielectrics for energy storage applications because of their high dielectric constant and high breakdown strength. However, these advantages are a trade-off with the unavoidable aggregation of the inorganic nanofillers, which result in a reduced discharge of the energy storage density. To address this problem, we developed polyvinylidene fluoride (PVDF) graft copolymer/cellulose-derivative composites to achieve high-dielectric and energy-storage density properties. An enhanced dielectric constant and improved energy density were achieved with this structure. The optimal composites exhibited a high discharge energy density of 8.40 J/cm3 at 300 MV/m. This work provides new insight into the development of all-organic composites with bio-based nanofillers.

HMGB3 Targeted by miR-145-5p Impacts Proliferation, Migration, Invasion, and Apoptosis of Breast Cancer Cells.

This study focused on the investigation into how HMGB3 works in breast cancer (BC) progression. Firstly, we analyzed the relationship between HMGB3 and BC patients through the TCGA database. We performed qRT-PCR for determining the HMGB3 mRNA level and Western blot for detecting the protein level of HMGB3 in BC cell lines. CCK-8, flow cytometry, transwell, and wound healing assays were utilized to detect the effect of HMGB3 on BC cell phenotypes. Next, the prediction of the binding site shared by miR-145-5p and HMGB3 was performed by the bioinformatics method. The targeting relationship between miR-145-5p and HMGB3 was validated by using dual-luciferase assay. Finally, rescue experiments were employed for assessing the effect of the miR-145-5p/HMGB3 axis on BC cells. HMGB3 was demonstrated to have a high-level expression in BC cell lines and facilitated BC progression. On the contrary, miR-145-5p was shown a low-level expression in BC cell lines, which could target HMGB3. miR-145-5p restrained the proliferation, migration, and invasion of BC cells via inhibiting HMGB3.

Research on the effect of interfering with miRNA-155 on triple-negative breast cancer cells.

BACKGROUND: Triple negative breast cancer (TNBC) is a poor prognosis breast cancer with the highest mutation rate and limited treatment options. MiR-155 is highly expressed in TNBC, but its role and potential mechanism in TNBC remain to be elucidated. OBJECTIVE: The aim of this study is to examine the effect of interfering with miRNA-155 on the inflammatory pathway of NLRP 3 in TNBC (MDA-MB-231). METHODS: MiRNA-155-specific interference (Si-miR-155) on MDA-MB-231 cell was manifested by transfection of miRNA-155 inhibitor. Meanwhile, blank control (Blank) and negative control (NC) were set. Cell growth and proliferation rate were detected by MTT; apoptosis rate were detected by flow cytometry; colony forming test was used to detected cell viability; cell migration ability was detected by Wound healing assay; TNF-α, IL-18, IL-6 and IL-1ß levels were detected by ELISA. The mRNA of miRNA-155, NLRP3, ASC, caspase-1 and Ki67 were detected by qRT-PCR. The expression levels of NLRP3, caspase-1, ASC and Ki67 were detected by Western blotting. RESULTS: The proliferation rate of Si-miRNA-155 group decreased, while the apoptosis rate increased significantly. After interfering with miRNA-155, the number of cancer cell colonies and the migration ability was decreased, and the secretion levels of IL-18, TNF-α, IL-6 and IL-1ß were also inhibited. Moreover the mRNA and protein expression of NLRP3, caspase-1, ASC and Ki67 were significantly suppressed. CONCLUSIONS: Interference with miRNA-155 can inhibit the NLRP3 pathway of MDA-MB-231 cells, as well as the proliferation, migration and inflammatory factor secretion of MDA-MB-231 cell, and can accelerate its apoptosis.

NFIB functions as an oncogene in estrogen receptor-positive breast cancer and is regulated by miR-205-5p.

Nuclear factor I/B(NFIB) is a prominent transcription factor that plays a critical role in cancer progression. In this study, we found that the protein level of NFIB was significantly upregulated in estrogen receptor (ER) positive breast cancer tissues compared to matched adjacent noncancerous tissues while the NFIB mRNA expression level was not obviously dysregulated. Similarly, ER-positive breast cancer cell line, MCF7 express a high protein level of NFIB, while the mRNA level is not significantly upregulated. The function assays indicated that NFIB promoted MCF-7 cell cycle progression, cell proliferation and suppressed apoptosis in vitro. Furthermore, we explored the molecular mechanisms of NFIB as a target gene of miR-205-5p. Finally, we found that miR-205-5p was significantly downregulated in ER -positive breast cancer, and had the opposite eff ;ects on breast cancer cells compared with NFIB. Taken together, this study highlighted the molecular mechanisms of NFIB as an oncogene in ER-positive breast cancer, which was negatively regulated by miR-205-5p in breast cancer.

Inhibition of DNA­PK by gefitinib causes synergism between gefitinib and cisplatin in NSCLC.

Lung cancer has the highest incidence and mortality rates among the malignant tumor types worldwide. Platinum­based chemotherapy is the main treatment for advanced non­small­cell lung cancer (NSCLC), and epidermal growth factor receptor­tyrosine kinase inhibitors (EGFR­TKIs) have greatly improved the survival of patients with EGFR­sensitive mutations. However, there is no standard therapy for treating patients who are EGFR­TKI resistant. Combining EGFR­TKIs and platinum­based chemotherapy is the most popular strategy in the clinical practice. However, the synergistic mechanism between EGFR­TKIs and platinum remains unknown. Therefore, the aim of the present study was to determine the synergistic mechanism of gefitinib (an EGFR­TKI) and cisplatin (a main platinum­based drug). MTT assay, apoptosis analysis, tumorsphere formation and an orthotropic xenograft mouse model were used to examine the combination effects of gefitinib and cisplatin on NSCLC. Co­immunoprecipitation and immunofluorescence were used to identify the underlying mechanism. It was found that gefitinib could selectively inhibit EGFR from entering the nucleus, decrease DNA­PK activity and enhance the cytotoxicity of cisplatin on NSCLC. Collectively, the results suggested that inhibition of DNA­dependent protein kinase by gefitinib may be due to the synergistic mechanism between gefitinib and cisplatin. Thus, the present study provides a novel insight into potential biomarkers for the selection of combination therapy of gefitinib and cisplatin.

QtUCP-a program for determining unit-cell parameters in electron diffraction experiments using double-tilt and rotation-tilt holders.

A computer program, QtUCP, has been developed based on several well-established algorithms using GCC 4.0 and Qt 4.0 (Open Source Edition) under Debian GNU/Linux 4.0r0. It can determine the unit-cell parameters from an electron diffraction tilt series obtained from both double-tilt and rotation-tilt holders. In this approach, two or more primitive cells of the reciprocal lattice are determined from experimental data, in the meantime, the measurement errors of the tilt angles are checked and minimized. Subsequently, the derived primitive cells are converted into the reduced form and then transformed into the reduced direct primitive cell. Finally all the patterns are indexed and the least-squares refinement is employed to obtain the optimized results of the lattice parameters. Finally, two examples are given to show the application of the program, one is based on the experiment, the other is from the simulation.

Differential expression patterns of Nqo1, AKR1B8 and Ho-1 in the liver and small intestine of C57BL/6 mice treated with sulforaphane.

This data article contains complementary figures and results related to the research article entitled "butylated hydroxyanisole induces distinct expression patterns of Nrf2 and detoxification enzymes in the liver and small intestine of C57BL/6 mice" (Luo et al., 2015 [1]), which defined the basal and butylated hydroxyanisole (BHA)-induced expression patterns of Phase II enzymes Nqo1, AKR1B8, and Ho-1 in the liver and small intestine of C57BL/6 mice. Sulforaphane [1-isothiocyanato-4-(methylsulfinyl)butane] (SFN), a naturally occurring isothiocyanate derived from cruciferous vegetables, is a highly potent inducer of phase II cytoprotective enzymes. This dataset reports the histological changes of Nqo1, AKR1B8, and Ho-1 in wild-type (WT) and Nrf2 (-/-) mice induced by SFN. The mice were given a 25 mg/kg single oral dose of SFN for 24 h and 48 h. Immunohistochemistry revealed that, in the liver from WT mice, SFN increased Nqo1 staining in hepatocytes with slight higher staining in the pericentral region. The induction of AKR1B8 appeared mostly in hepatocytes in the periportal region. The basal and inducible Ho-1 was located predominately in Kupffer cells. In the small intestine from WT mice, the inducible expression of Nqo1 and AKR1B8 appeared more obvious in the villus than that in the crypt.