CREB1 contributes colorectal cancer cell plasticity by regulating lnc RNA CCAT1 and NF-κB pathways

The CREB1 gene encodes an exceptionally pleiotropic transcription factor that frequently dysregulated in human cancers.CREB1 can regulate tumor cell status of proliferation and/or migration;however,the molecular basis for this switch involvement in cell plasticity has not fully been understood yet.Here,we first show that knocking out CREB1 triggers a remarkable effect of epithelial-mesenchymal transition(EMT)and leads to the occurrence of inhibited proliferation and enhanced motility in HCT116colorectal cancer cells.By monitoring 45 cellular signaling pathway activities,we find that multiple growth-related pathways decline significantly while inflammatory pathways including NF-κB are largely upregulated in comparing between the CREB1wild-type and knocked out cells.Mechanistically,cells with CREB1 knocked out show downregulation of MYC as a result of impaired CREB1-dependent transcription of the oncogenic lnc RNA CCAT1.Interestingly,the unbalanced competition between the coactivator CBP/p300 for CREB1 and p65 leads to the activation of the NF-κB pathway in cells with CREB1 disrupted,which induces an obvious EMT phenotype of the cancer cells.Taken together,these studies identify previously unknown mechanisms of CREB1 in CRC cell plasticity via regulating lnc RNA CCAT1 and NF-κB pathways,providing a critical insight into a combined strategy for CREB1-targeted tumor therapies.

Ephrin A2 protein expression in the regeneration and plasticity of cochlear hair cells in chicken following kanamycin ototoxicity

The results from this study showed that the thresholds of brainstem auditory-evoked potentials peak following 10 successive days of intramuscular injection of Roman chickens with kanamycin, starting 3 days after birth. Fluorescence immunohistochemistry analysis revealed few ganglion cells positively labeled for Ephrin A2 in the cochlea of experimental chickens from 2 days before until 7 days after the last kanamycin injection. The number of Ephrin A2-positive ganglion cell bodies was increased at 15 days after the last injection and was similar to that in normal chickens at 30 days following the cessation of kanamycin treatment. These experimental findings indicate that Ephrin A2 protein expression in the acoustic ganglia is synchronized with the connection damage and regeneration of cochlear hair cells after kanamycin exposure. Ephrin A2 may play an important role in the regeneration and plasticity of cochlear hair cells in the chick cochlea following kanamycin ototoxicity.

Magnetic resonance imaging and cell-based neurorestorative therapy after brain injury

Restorative cell-based therapies for experimental brain injury, such as stroke and traumatic brain injury,substantially improve functional outcome. We discuss and review state of the art magnetic resonance imaging methodologies and their applications related to cell-based treatment after brain injury. We focus on the potential of magnetic resonance imaging technique and its associated challenges to obtain useful new information related to cell migration, distribution, and quantitation, as well as vascular and neuronal remodeling in response to cell-based therapy after brain injury. The noninvasive nature of imaging might more readily help with translation of cell-based therapy from the laboratory to the clinic.

Cellular plasticity and metastasis in breast cancer: a pre- and post-malignant problem

As a field we have made tremendous strides in treating breast cancer,with a decline in the past 30 years of overall breast cancer mortality.However,this progress is met with little affect once the disease spreads beyond the primary site.With a 5-year survival rate of 22%,10-year of 13%,for those patients with metastatic breast cancer(mBC),our ability to effectively treat wide spread disease is minimal.A major contributing factor to this ineffectiveness is the complex make-up,or heterogeneity,of the primary site.Within a primary tumor,secreted factors,malignant and pre-malignant epithelial cells,immune cells,stromal fibroblasts and many others all reside alongside each other creating a dynamic environment contributing to metastasis.Furthermore,heterogeneity contributes to our lack of understanding regarding the cells'remarkable ability to undergo epithelial/non-cancer stem cell(CSC)to mesenchymal/CSC(E-M/CSC)plasticity.The enhanced invasion&motility,tumor-initiating potential,and acquired therapeutic resistance which accompanies E-M/CSC plasticity implicates a significant role in metastasis.While most work trying to understand E-M/CSC plasticity has been done on malignant cells,recent evidence is emerging concerning the ability for pre-malignant cells to undergo E-M/CSC plasticity and contribute to the metastatic process.Here we will discuss the importance of E-M/CSC plasticity within malignant and pre-malignant populations of the tumor.Moreover,we will discuss how one may potentially target these populations,ultimately disrupting the metastatic cascade and increasing patient survival for those with mBC.

Synthesis and characterization of novel low band-gap polymers containing squaraine units

Novel conjugated polymers based on squaric acid having 2,5-Bis[（E）-N-alkylpyrrol-2-ylvinyl]-3-alkylthiophene （PVTVP） unit in the main chain were successfully synthesized in good yields through polycondensation reaction. Their molecular structures were characterized by PT-IR and IH NMR. They have good solubility in common organic solvents, good thermal stability by thermal gravimetric analysis and high molecular weights. Their optical properties were investigated by UV-vis absorption spectra in CH2C12 solution, the results indicated all these compounds showed broad and strong spectral responses from 200 nm to 900 nm, suggesting their potential for application as organic plastic solar cells.

Cancer stem cells may contribute to the difficulty in treating cancer

Tumour heterogeneity is a phenomenon where each cell that makes up a tumour,contains mutations that differ from that of other cells in the tumour.The clonal evolution and cancer stem cell theories of cancer formation,have been used to explain tumour heterogeneity.The theories both point to the existence of cells within a tumour that are capable of initiating the tumour in a different location.While the clonal evolution theory argues that all cells within a tumour possess this ability,the cancer stem cell theory argues that only a few cells(cancer stem cells or CSCs)within the tumour possess this ability to seed the tumour in a different location.Data supporting the cancer stem cell theory is accumulating.Researchers have targeted these CSCs therapeutically,hypothesizing that since these CSCs are the‘drivers’of tumour progression,their death may inhibit tumour progression.This was foiled by tumour cell plasticity,a phenomenon whereby a non-CSC spontaneously de-differentiates into a CSC.Researchers are now working on combinations that kill both CSCs and non-CSCs as well as drugs that prevent non-CSC-to-CSC transition.This review concisely describes CSCs and how they contribute to the difficulty in treating cancer.

Dual recombinases-based genetic lineage tracing for stem cell research with enhanced precision

Stem cell research has become a hot topic in biology,as the understanding of stem cell biology can provide new insights for both regenerative medicine and clinical treatment of diseases.Accurately deciphering the fate of stem cells is the basis for understanding the mechanism and function of stem cells during tissue repair and regeneration.Cre-loxP-mediated recombination has been widely applied in fate mapping of stem cells for many years.However,nonspecific labeling by conventional cell lineage tracing strategies has led to discrepancies or even controversies in multiple fields.Recently,dual recombinase-mediated lineage tracing strategies have been developed to improve both the resolution and precision of stem cell fate mapping.These new genetic strategies also expand the application of lineage tracing in studying cell origin and fate.Here,we review cell lineage tracing methods,especially dual genetic approaches,and then provide examples to describe how they are used to study stem cell fate plasticity and function in vivo.

Effects of test levels on creep and relaxation characteristic parameters of stem for rice seedlings grown in plastic cell tray

Creep and relaxation characteristics of stem for rice seedlings grown in plastic cell tray were studied by static tensile testing,in order to determine the relationship between characteristic parameters(rheological model parameters,stress components and strain components)and test levels(stress levels and strain levels).Rice seedling stem specimen used in the test was 40 mm in length.And the applied test values for the creep and relaxation test ranged from 1.0-3.0 MPa and 1.5%-3.5%,respectively,each for 5 levels.The results indicated that elastic modulus in the creep and relaxation model was not affected by test levels.However,except that viscosity coefficientηkv was a constant andηm1 decreased with the increase of test levels,other viscosity coefficient and rheological time nonlinearly increased as the test levels increased.And strain components in the creep model and stress components in the relaxation model significantly increased as the test levels increased.

When fats commit crimes: fatty acid metabolism, cancer stemness and therapeutic resistance

The role of fatty acid metabolism,including both anabolic and catabolic reactions in cancer has gained increas-ing attention in recent years.Many studies have shown that aberrant expression of the genes involved in fatty acid synthesis or fatty acid oxidation correlate with malignant phenotypes including metastasis,therapeutic resistance and relapse.Such phenotypes are also strongly associated with the presence of a small percentage of unique cells among the total tumor cell population.This distinct group of cells may have the ability to self-renew and propagate or may be able to develop resistance to cancer therapies independent of genetic alterations.Therefore,these cells are referred to as cancer stem cells/tumor-initiating cells/drug-tolerant persisters,which are often refractory to cancer treatment and difficult to target.Moreover,interconversion between cancer cells and cancer stem cells/tumor-initiating cells/drug-tolerant persisters may occur and makes treatment even more challenging.This review highlights recent findings on the relationship between fatty acid metabolism,cancer stemness and therapeutic resistance and prompts discussion about the potential mechanisms by which fatty acid metabolism regulates the fate of cancer cells and therapeutic resistance.

Endogenous repair theory enriches construction strategies for orthopaedic biomaterials:a narrative review

The development of tissue engineering has led to new strategies for mitigating clinical problems;however,the design of the tissue engineering materials remains a challenge.The limited sources and inadequate function,potential risk of microbial or pathogen contamination,and high cost of cell expansion impair the efficacy and limit the application of exogenous cells in tissue engineering.However,endogenous cells in native tissues have been reported to be capable of spontaneous repair of the damaged tissue.These cells exhibit remarkable plasticity,and thus can differentiate or be reprogrammed to alter their phenotype and function after stimulation.After a comprehensive review,we found that the plasticity of these cells plays a major role in establishing the cell source in the mechanism involved in tissue regeneration.Tissue engineering materials that focus on assisting and promoting the natural self-repair function of endogenous cells may break through the limitations of exogenous seed cells and further expand the applications of tissue engineering materials in tissue repair.This review discusses the effects of endogenous cells,especially stem cells,on injured tissue repairing,and highlights the potential utilisation of endogenous repair in orthopaedic biomaterial constructions for bone,cartilage,and intervertebral disc regeneration.