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At least 1,063 records · Page 59

ZEB1 stimulates breast cancer growth by up-regulating hTERT expression

Highlights: • hTERT expression is positively correlated with ZEB1 expression in breast cancer. • ZEB1 promotes hTERT expression and telomerase activity in breast cancer cell lines. • ZEB1 increases the transcriptional activity of the hTERT promoter but does not bind to the E-box. • ZEB1 controls hTERT expression by interacting with the co-activator Yes-associated protein (YAP). Dysfunctional cell proliferation and death are the foundation of the malignant biological characteristics of cancers. In this study, we discovered that ZEB1 was positively correlated with hTERT in breast invasive ductal carcinoma samples at both the mRNA and protein levels. Further, our in vitro study in breast cancer cell lines confirmed that ZEB1 regulates hTERT expression at the mRNA and protein levels; thus, hTERT promotes or inhibits telomerase activity, and telomere length is either protected or reduced. Finally, we verified that ZEB1, which mostly functions as a transcriptional repressor, can recruit the co-activator YAP to enhance the transcriptional activation of hTERT. Fascinatingly, instead of acting on E-boxes, the ZEB1/YAP complex tends to function as a transcriptional activator by binding with sequences potentially located in the hTERT promoter. Consequently, our research revealed a new ZEB1-hTERT signaling pathway involved in cell proliferation regulation that has never before been illuminated in breast cancer.

60 APPLIED LIFE SCIENCES↗

Reversion of aging-related DHEAS decline in mouse plasma alleviates aging-related glucose tolerance impairment by potentiation of glucose-stimulated insulin secretion of acute phase

Highlights: • Aging-related DHEAS decline in mouse plasma contribute to aging-related impairment of glucose tolerance. • Reversion of aging-related DHEAS deficiency in aging mice could alleviate aging-related glucose tolerance impairment. • In vitro, physical concentration of DHEAS potentiated GSIS of acute phase in aging mice pancreatic islets and MIN6 cells. The latest research proposes mild age-related diabetes (MARD) as a subgroup of type 2 diabetes. While in human circulating dehydroepiandrosterone sulfate (DHEAS) decline with age is related to MARD, the role of circulating DHEAS in insulin secretion remains little known.

60 APPLIED LIFE SCIENCES↗

Mechanical stress to Drosophila larvae stimulates a cellular immune response through the JAK/STAT signaling pathway

Acute inflammation can cause serious tissue damage and disease in physiologically-challenged organisms. The precise mechanisms leading to these detrimental effects remain to be determined. In this study, we utilize a reproducible means to induce cellular immune activity in Drosophila larvae in response to mechanical stress. That is, forceps squeeze-administered stress induces lamellocytes, a defensive hemocyte type that normally appears in response to wasp infestation of larvae. The posterior signaling center (PSC) is a cellular microenvironment in the larval hematopoietic lymph gland that is vital for lamellocyte induction upon parasitoid attack. However, we found the PSC was not required for mechanical stress-induced lamellocyte production. In addition, we observed that mechanical injury caused a systemic expression of Unpaired3. This cytokine is both necessary and sufficient to activate the cellular immune response to the imposed stress. These findings provide new insights into the communication between injured tissues and immune system induction, using stress-challenged Drosophila larvae as a tractable model system.

60 APPLIED LIFE SCIENCES↗

Allethrin and prallethrin stimulates MUC5AC expression through oxidative stress in human airway epithelial cells

Highlights: • Allethrin and prallethrin are implicated in modulation of airway mucin secretion. • Allethrin and prallethrin induce MUC5AC expression. • Allethrin and prallethrin induce MUC5AC expression via ROS. Pyrethroids, including allethrin and prallethrin, have been widely used as major components of the common commercial insecticides. The toxicity of allethrin and prallethrin were well established that it interfered with the way that the nerves and brain function. However, limited information was available regarding respiratory effects in humans following inhalation exposure to allethrin and prallethrin. Therefore, we demonstrated effect of allethrin and prallethrin, and the mechanism involved, on the mucin expressions in human airway epithelial cells. In human airway NCI-H292 epithelial cells, the effects of allethrin and prallethrin and its signaling pathway for airway mucin, especially MUC5AC, were investigated by reverse transcriptase-polymerase chain reaction (RT-PCR), real-time PCR, and enzyme-linked immunosorbent assay (ELISA). The mechanism of allethrin and prallethrin-induced MUC5AC expression in airway epithelial cells was studied in terms of reactive oxygen species (ROS) by flow cytometry analysis. Allethrin and prallethrin significant increased MUC5AC expression in human airway NCI-H292 epithelial cells. We also demonstrated allethrin and prallethrin induced a marked rise of ROS production. In addition, NAC (ROS scavenger) and DPI (NADPH oxidase inhibitor) inhibited allethrin and prallethrin-induced MUC5AC expression. These results are first to describe that allethrin and prallethrin-induced MUC5AC expression through ROS in human airway epithelial cells.

60 APPLIED LIFE SCIENCES↗

Berberine derivative, Q8, stimulates osteogenic differentiation

Highlights: • Q8 increases BMP4-induced osteoblast differentiation of C2C12 cells. • Q8 induced β-catenin nuclear accumulation by enhancing GSK3β phosphorylation via inactivation of PPARγ. • Q8 ameliorated the inhibitory effects of rosiglitazone during osteoblast differentiation. Berberine has been implicated to be involved in maintaining bone health due to its anti-oxidative and osteogenic properties. However, low potency and low bioavailability limit the clinical development of the drug. To overcome these obstacles, we previously synthesized a compound, Q8, which is a structural homolog of berberine. The present study examined the pharmacological functions of Q8 to evaluate its potential use in bone regeneration with respect to osteoblast differentiation. Here, we report that Q8 enhanced BMP4-induced alkaline phosphatase (ALP) activity and transcription from the ALP promoter. In addition, Q8 suppressed the expression and activity of PPARγ (a known negative regulator of osteogenesis due to its stimulatory effects on adipogenesis and its role as an adipogenic transcription factor), which in turn increases β-catenin expression in the nucleus, and ultimately promotes osteoblast differentiation. Meanwhile, Q8 reversed the inhibitory effects of the PPARγ agonist, rosiglitazone, on osteoblast differentiation. This study demonstrated that Q8 promotes osteoblast differentiation via inhibition of PPARγ and the enhancement of osteoblast function by Q8 may contribute to the prevention for osteoporosis.

60 APPLIED LIFE SCIENCES↗

p-Coumaric acid stimulates longitudinal bone growth through increasing the serum production and expression levels of insulin-like growth factor 1 in rats

The aim of the present study was to examine the effects of p-coumaric acid on the longitudinal growth of the long bone in adolescent male rats. Teatment with p-coumaric acid significantly increased the tibial length and the height of each growth plate zone and the ratio of 5-bromo-2′-deoxyuridine-positive cells relative to total proliferative cells. Expression of insulin-like growth factor 1 and its receptor in the proliferative and hypertrophic zones, and serum levels of growth hormone and insulin-like growth factor 1 were significantly increased as well in the p-coumaric acid-treated group. Via increasing both the serum level of insulin-like growth factor 1 and its expression, p-coumaric acid could promote cell proliferation in growth plate zones. These results suggest that p-coumaric acid has the potential to increase height and may be a feasible alternative to growth hormone therapy.

60 APPLIED LIFE SCIENCES↗

(Phospho)Proteomic dataset of ischemia- and ultrasound- stimulated mouse cardiac endothelial cells in vitro

Cardiac endothelial cells respond to both ischemia and therapeutic ultrasound; the proteomic changes underlying these responses are unknown. This data article provides raw and processed data resulting from our global, unbiased phosphoproteomics investigation conducted on primary mouse cardiac endothelial cells exposed to ischemia (2-hour oxygen glucose deprivation) and ultrasound (250 kHz, 1.2 MPa) in vitro [1]. Proteins were extracted from cell lysates and enriched phosphopeptides were analyzed with a high mass accuracy liquid chromatrography (LC) - tandem mass spectrometry (MS/MS) proteomic platform, yielding multiple alterations in both total protein levels and phosphorylation events in response to ischemic injury and ultrasound. This dataset can be used as a reference for future studies on the cardiac endothelial response to ischemia and the mechanistic underpinnings of the cellular response to ultrasound, with the potential to yield clinically relevant therapeutic targets.

59 BASIC BIOLOGICAL SCIENCES↗

Optimal design of 3D borehole seismic arrays for microearthquake monitoring in anisotropic media during stimulations in the EGS collab project

Multiple U.S. national laboratories, universities and industrial collaborators are conducting collaborative research under the EGS Collab project supported by the U.S. Department of Energy, to understand the fracture creation and imaging during fracturing in enhanced geothermal systems. Microearthquake hypocenter locations and focal mechanisms are used to monitor hydraulic fracturing growth and characterization at the EGS Collab experimental site at the Sanford Underground Research Facility using seismic receivers in multiple monitoring wells. In this study, we develop a methodology for optimal design a 3D borehole seismic array for cost-effective seismic monitoring in anisotropic media using not only the relationship between receiver distributions and standard deviation errors of microearthquake hypocenter locations, but also that between receiver distributions and focal-mechanism inversion errors. Our results indicate that microearthquake hypocenter locations and focal mechanisms can be reasonably well reconstructed for the EGS Collab Experiment I using six monitoring wells, including four fracture-parallel monitoring wells and two orthogonal wells. Lastly, eight seismic receivers evenly distributed in four parallel monitoring wells or twelve receivers in all six monitoring wells are required for hypocenter location, and twelve receivers evenly distributed in six wells or sixteen receivers in four wells are needed for focal-mechanism inversion.

58 GEOSCIENCES↗

Induced seismicity during the 2012 Newberry EGS stimulation: Assessment of two advanced earthquake detection techniques at an EGS site

To improve the microearthquake detection capability during the 2012 Newberry enhanced geothermal system (EGS) demonstration, we applied two advanced earthquake detection algorithms to the continuous seismic data. These techniques have the power to detect microearthquakes within the seismic noise that would otherwise be missed using traditional techniques. We compare the efficacy of a matched field processing algorithm with a multi-channel waveform correlation algorithm. Both methods identified between 60%–80% more events, with each slightly outperforming the other in different seismic noise contexts. Incorporating either template-matching technique into a seismic processing routine could therefore effectively increase the sensitivity of the seismic network without changes to the existing hardware. Additionally, lowering the magnitude of completeness would significantly add to the number of events that could subsequently inform future decision making at the reservoir level.

15 GEOTHERMAL ENERGY↗