386 research outputs found
Aldehyde Dehydrogenase 1 and Raf Kinase Inhibitor Protein Expression Defines the Proliferative Nature of Cervical Cancer Stem Cells
Purpose: To determine the differences in response following the use of aldehyde dehydrogenase 1 (ALDH1) and Raf kinase inhibitor protein (RKIP) as cervical cancer stem cell markers.Methods: To evaluate the cancer stem cell markers, a mouse model with low and high grade cervical cancer was developed and studied by histological examination. Immunohistochemical and Western blotting techniques were employed to study the expression profiles of ALDH1 and RKIP. The specificity of Sox2 that determines cancer stem cells served as control to validate ALDH1 and RKIP expressions.Results: Histological data helped to differentiate low from high grade cervical cancer. The results from immunohistochemistry show increased pattern of Sox2 expression as tumour progresses. Similarly, ALDH1, a protein that positively regulates stem cells shows mild expression in low grade cervical tumour, but positive signals are more amplified in an aggressive stage of tumour condition when compared with Sox2. The expression study with RKIP, a protein that negatively regulates stem cells, interestingly defines the higher expression in low grade cervical cancer to regulate the tumour, but shows little or no very mild expression in the aggressive stage of tumour. All the data obtained show a statistically significant value of p < 0.05. The results with Immunohistochemistry were further validated using the western blotting analysis and it also confirms the similar results.Conclusion: ALDH1 and RKIP marker in association correlation with Sox2 aids in defining the proliferative ability of cervical cancer stem cells and also to validate them in initial and advanced stages of cervical cancer.Keywords: Cervical cancer, ALDH1, BALB/c-nu/nu, HeLa cells, RKIP, Sox
Dichlorido(dipyrido[3,2-a:2âČ,3âČ-c]phenazine)manganese(II)
The complete molÂecule of the title compound, [MnCl2(C18H10N4)2], is generated by crystallographic twofold symmetry with the Mn atom lying on the rotation axis. The Mn coordination geometry is a distorted cis-MnCl2N4 octaÂhedron, arising from two N,NâČ-bidentate dipyrido[3,2-a:2âČ,3âČ-c]phenazine (DPPZ) ligands and two chloride ions. In the crystal structure, neighbouring mononuclear units pack together through ÏâÏ contacts between the DPPZ rings [shortest centroidâcentroid distance = 3.480â
(2)â
Ă
], leading to a chain-like structure along [001]. CâHâŻCl hydrogen bonds complete the structure
Cationic liposomes induce cytotoxicity in HepG2 via regulation of lipid metabolism based on whole-transcriptome sequencing analysis
Abstract
Backgroud
Cationic liposomes (CLs) can be used as non-viral vectors in gene transfer and drug delivery. However, the underlying molecular mechanism of its cytotoxicity has not been well elucidated yet.
Methods
We herein report a systems biology approach based on whole-transcriptome sequencing coupled with computational method to identify the predominant genes and pathways involved in the cytotoxicity of CLs in HepG2 cell line.
Results
Firstly, we validated the concentration-dependent cytotoxicity of CLs with an IC50 of 120Â ÎŒg/ml in HepG2 exposed for 24Â h. Subsequently, we used whole-transcriptome sequencing to identify 220 (77 up- and 143 down-regulated) differentially expressed genes (DEGs). Gene ontology (GO) and pathway analysis showed that these DEGs were mainly related to cholesterol, steroid, lipid biosynthetic and metabolic processes. Additionally, âkey regulatoryâ genes were identified using gene act, pathway act and co-expression network analysis, and expression levels of 11 interested altered genes were confirmed by quantitative real time PCR. Interestingly, no cell cycle arrest was observed through flow cytometry.
Conclusions
These data are expected to provide deep insights into the molecular mechanism of CLs cytotoxicity.https://deepblue.lib.umich.edu/bitstream/2027.42/144776/1/40360_2018_Article_230.pd
Baicalein inhibits acinar-to-ductal metaplasia of pancreatic acinal cell AR42J via improving the inflammatory microenvironment
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers. Recent research has demonstrated that chronic pancreatitis (CP) is associated with an increased risk of PDAC, partly due to acinar-to-ductal metaplasia (ADM). Baicalein has been shown to exert anti-inflammatory and anti-tumor effects for CP or PDAC, respectively. The aim of our study was to investigate the effect of baicalein, and the putative underlying mechanism, on inflammatory cytokines-induced ADM of rat pancreatic acinar cell line AR42J. To investigate ADM and baicalein effects in vitro, AR42J were treated with recombinant rat Tumor Necrosis Factor alpha (rTNFα) with or without baicalein for 5 days. Results showed that rTNFα-induced AR42J cells switched their phenotype from dominantly amylase-positive acinar cells to dominantly cytokeratin 19-positive ductal cells. Moreover, expression of the transcripts for TNFα or Hes-1, a Notch target, was up-regulated in these cells. Interestingly, baicalein reduced the population of ADM as well as cytokines gene expression but not Hes-1. Baicalein inhibited NF-ÎșB activation induced by rTNFα in AR42J, but no effect on Notch 1activation. Moreover, baicalein suppressed the secretion of TNFα and Nitric Oxide (NO) in macrophages stimulated with LPS and further inhibited ADM of conditional medium-treated AR42J cells. Baicalein also suppressed the inflammatory response of LPS-activated macrophages, thereby inhibited ADM of AR42J by altering their microenvironment. Taken together, our study indicates that baicalein reduces rTNFα-induced ADM of AR42J cells by inhibiting NF-ÎșB activation. It also sheds new light on Chinese material medica therapy of pancreatitis and thereby prevention of PDAC
Cuprous oxide nanoparticles inhibit prostate cancer by attenuating the stemness of cancer cells via inhibition of the Wnt signaling pathway
Effects of surface charges of gold nanoclusters on long-term in vivo biodistribution, toxicity, and cancer radiation therapy
Women Under Kuomintang R ule Variations on the Feminine Mystique
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68360/2/10.1177_009770047500100101.pd
Atomically-precise lanthanide-iron-oxo clusters featuring the Δ-Keggin ion.
Atomically precise molecular metal-oxo clusters provide ideal models to understand metal oxide surfaces, self-assembly, and form-function relationships. Devising strategies for synthesis and isolation of these molecular forms remains a challenge. Here, we report the synthesis of four Ln-Fe oxo clusters that feature the Δ -{Fe 13 } Keggin cluster in its core. The {Fe 13 } metal-oxo cluster motif is the building block of two important iron oxyhydroxyide phases in nature and technology, ferrihydrite (as the Ύ -isomer) and magnetite (the Δ -isomer). The reported Δ -{Fe 13 } Keggin isomer as an isolated molecule provides opportunity to study the formation of ferrihydrite and magnetite from this building unit. The next metal layer surrounding the Δ -{Fe 13 } core within these clusters exhibit a similar arrangement as the magnetite lattice, and Fe and Ln can occupy the same positions. This provides opportunity to construct a family of compounds and optimize magnetic exchange in these molecules via composition tuning. Small angle X-ray scattering (SAXS) and high-resolution electrospray ionization mass spectrometry (HRESI-MS) show these clusters are stable upon dissolution in both water and organic solvents, as a first step to perform further chemistry towards building magnetic arrays or invetigating ferrihydrite and magnetite assembly from pre-nucleation clusters
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