The present work has identified gene expression signatures which can distinguish quiescence from senescence. Additionally the work has identified ARID5A as a quiescence associated gene.

We identified a high throughput method to study various aspects of the physiology of E2:ERα signaling in a contemporary manner. We identified methotrexate as a drug inducing ERα degradation and preventing breast cancer cell proliferation.

Breast cancer (BC) is the most prevalent cancer in women worldwide. Epithelial–Mesenchymal Transition (EMT) enables the invasion of metastatic cancer cells. Recent evidence demonstrates that aberrantly DNA methylation of miRNAs controls miRNA expression. Therefore, epigenetic controlling of EMT-involving miRNAs are important in diagnosis and therapeutic of BC.

The present mini-review summarizes the most recent data on the role of mtROS in the antibacterial immunity. The principles of mtROS formation and possible mechanisms of their generation under the activation of innate immunity are highlighted in this review. We also speculate on the possibilities of using activators of mtROS production in clinical practice.

In this review, we evaluate the involvement of calcium-activated potassium channel subtypes in mesenchymal stem cell differentiation. We propose a new model showing how intracellular calcium and membrane potential oscillations are generated and can contribute dynamically to the differentiation process. Finally, we highlight various mechanisms, including network interactions, fine tuning terminal differentiation.

The skeleton has recently emerged as a critical insulin target tissue that regulates whole body glucose metabolism and male reproductive function. While our understanding of these new skeletal functions remains in its infancy, the bone-specific protein, osteocalcin, has been shown to be centrally involved in both processes. This review examines recent data emerging from transgenic mouse models and human clinical studies which have revealed a novel pancreas-bone-testis regulatory axis, and discusses the potential role of bone specific mTORC1 signaling in the regulation of systemic glucose metabolism.

Systematic signaling pathological cascade associated with pulmonary hypertension.

The current study was focused on bio-imitating the tissue engineering of the pancreas by employing an acellular pancreatic tissue as a non-immunogenic bioscaffold to be used as a novel surgical technique for in vivo tissue regeneration, as well as the unique utilization of the omentum as a bioreactor.

This review summarizes the current knowledge regarding the role of miRNAs expression in OC. It also provides information about potential clinical relevance of circulating miRNAs for OC diagnosis, prognosis, and therapeutics. The identification of functional targets for miRNAs represents a major obstacle in our understanding of microRNA function in OC, but significant progress is being made. The better understanding of the role of microRNA expression in ovarian cancer may provide new array for the detection, diagnosis, and therapy of the OC.

After abnormal regulation of these molecules in the basal cells of the esophagus occurs, multiple diseases, including esophageal atresia with or without tracheoesophageal fistula, Barrett esophagus, gastroesophageal reflux, and eosinophilic esophagitis, will take place as a result. Furthermore, expression changes of signal molecules or signal pathways in basal cells and the microenvironment around basal cells both can initiate the switch of malignant transformation.

Under ER stress condition, the ER stress-mediated autophagy and ER-phagy can be activated, and both involved in UPR and the core autophagy machinery. However, the determined factors that control the changeover switch between ER stress-mediated autophagy and ER-phagy, are unclear. And we speculate that the type of cells and the extent of stimulation may be associated with the type of autophagy induced by ER stress.

In this prospect article, after highlighting recent developments of CRISPR systems, we outline different applications and current limitations of CRISPR use in biological and biomedical investigation. Finally, we provide a perspective for future development and potential risks of this multifunctional technology.

Studies show that apelin mRNA is highly expressed in the inner stripe of kidney outer medulla, which plays an important role in process of water and sodium balance. Additionally, more studies also indicate that apelin/APJ system may exerts a broad range of activities in kidney. Therefore, we review the role of apelin/APJ system in kidney diseases such as renal fibrosis, renal ischemia/reperfusion injury, diabetic nephropathy, polycystic kidney disease, and hemodialysis.

Endothelial colony forming cells (ECFCs) isolated from peripheral blood display (PB-ECFCs) a lower pro-angiogenic response to VEGF as compared to those deriving from umbilical cord blood (UCB-ECFCs). The Ca2+ permeable channel TRPC3 initiates VEGF-induced pro-angiogenic Ca2+ oscillations in UCB-ECFCs. We discuss the possibility to use TRPC3 to improve the reparative potential of autlogous ECFCs in cell based therapy of failing heart.

IL-21 possess the potential to activate various signaling pathways including STAT-3, PI3K/Akt, MAPK and several other downstream elements resulting in aberrant cellular proliferation and inflammatory processes in RA pathogenesis

The activation/inhibition of mTOR signaling can positively/negatively regulate bone marrow mesenchymal stem cells (BMSCs)/osteoblasts-mediated bone formation, adipogenic differentiation, osteocytes homeostasis, and osteoclasts-mediated bone resorption, which result in the changes of bone homeostasis, thereby resulting in or protect against osteoporosis.

We found that fraxinellone administration caused growth arrest and certainly repressed the activity of senescence-associated β-galactosidase as well as the expression of senescence-associated genes. Interestingly, this effect of fraxinellone is closely correlated with the restoration of impaired autophagy and the activation of AMPK. Notably, fraxinellone reacts in an AMPK-dependent but mTORC1-independent manner.

NDs and tumors are severe, disabling, progressive, and often incurable conditions, and represent a pressing problem in terms of human suffering and economic costs to the healthcare systems. Recently, the scientific community has focused on the beneficial effects of dietary antioxidant classes, such as polyphenols, in neurodegeneration and tumor prevention. Pre-clinical and clinical evidence shows that polyphenolic compounds are safe and able to interact in synergy with commonly used therapeutic treatment.

The review focuses on studies using Mesenchymal Stem Cells in therapeutic strategies for chronic neurological disorders such as Alzheimer's Disease, Amyotrophic Lateral Sclerosis, Huntington's Disease, and Parkinson's Disease. The main findings obtained by in vitro and in vivo experiments, as well as in clinical trials are outlined. Possible stem cell mediated mechanisms of action are discussed.

Melatonin is one of the best antioxidants that protects liver. Melatonin exerts its antioxidative function directly through its radical scavenging ability and indirectly through stimulation of antioxidant enzymes. This indoleamine is also an effective and promising antioxidative choice for targeting liver IRI, NAFLD, NASH, fibrosis, cirrhosis, and HCC.

lncRNA-PVT1 functions as an endogenous “sponge” by competing for miR-448 binding to regulate the miRNA target SERBP1 and, therefore, promotes the proliferation and migration of PC cells.

Our results indicate that high Pi levels trigger aortic calcification and modulation of certain miRs.

We identified 96 differentially expressed genes in patients with type II diabetes and these genes were enriched in the response to glucocorticoid. Seven genes belonging to this term, including UBE2L3, PTPRU, UCP3, TFAP4, CDKN1A, ATP2B1, and ZFP36L1, might play critical role in the progression of diabetes and they might perform as targets of treatment. The network-based analysis also suggested the existed drug might also work for diabetes.

Our study demonstrate that BMP-7 attenuates the hypoxia-induced EndoMT and cell migration by suppressing the m-TORC1 signaling pathway. We revealed a novel mechanism underlying the hypoxia-induced EndoMT in pulmonary artery endothelial cells and suggested a new therapeutic strategy targeting EndoMT for the treatment of pulmonary arterial hypertension.

A covalent complex (S–S linkage) between the pseudo-peptide N6L and the toxin Saporin (SAP-N6L) binds nucleolin on the surface of glioblastoma cells and once internalized induces cell death via apoptosis through inhibition of protein synthesis.

We introduce here a new parameter for the analysis of growth inhibition in cell proliferation assays, termed relative population doubling capacity, that can be used to properly quantify and compare the anti-proliferative activity of tested compounds on exponential growing cell models.

Our work describes the potentially important medical application of the nutrient flavonoid quercetin in overcoming the toxic effects of radiocontrast media in human renal cells. The mechanism of action is in part by modulation of important cellular signaling molecules.

Our findings in LUAD cell lines and xenografts support the use of DGCR5 as an oncogene to promote LUAD development. This is the first reporting of a possible mechanism for a crosstalk between DGCR and hsa-mir-22-3p crosstalk in LUAD. These results suggest DGCR5 as a potential target for LUAD treatment.

In this study, we have characterized the newly discovered trans-spliced products of the JC virus late transcripts, designated as new ORFs. We demonstrated that the 5′-coding region of the VP1 is trans-spliced between the coding regions of Agnoprotein and VP1 creating new open reading frames, ORF1 and ORF2, each of which is capable of encoding a 58 and 72 aa long, respectively. Each ORF protein shares a common coding region with VP1 and has a unique coding sequence of their own. When the expression of the unique coding regions of ORFs is blocked by a stop codon insertion in the viral background, the mutant virus replicates less efficiently when compared to wild-type, suggesting that the newly discovered ORFs play critical roles in the JCV life cycle.

Concanavalin A (ConA)-induced hepatitis is an experimental model of human autoimmune hepatitis induced in rodents by i.v. injection of Con A. Our data indicate that the Nrf2/HO-1/CO pathway is involved in autoimmune hepatitis and that therapeutic intervention using the Carbon Monoxide releaser,CORM-A1, may represent a novel strategy to be considered for the treatment of autoimmune hepatitis in humans.

Two dimensional protein profiles in serum-deprived NIH3T3 cells revealed the upregulation of Gas1, Anxa1, Anxa 2, Dyrk 1B. Further experiments with GAS1-overexpressing cells demonstrated that GAS1 induces the upregulation of Anxa1, Anxa 2 and Dyrk 1B. Finally, we provide evidence showing that GAS1, through Dyrk 1B, leads not only NIH3T3 cells to cell arrest but also maintains cell viability.

NOD1 acts on the serotonergic system decreasing SERT activity and molecular expression. Additionally, NOD1 expression seems to be modulated by 5-HT and other immune receptors as TLR2 and TLR4.

Our results indicate that estrogen prevents osteoporosis by promoting stemness and osteogenesis, and inhibiting senescence of BMSCs through an ERβ-SATB2 pathway.

HBP1 regulates adipocyte differentiation. Upon MDI stimulation, HBP1 expression is down-regulated at the beginning of the MCE to ensure the up-regulation of C/EBPβ and allows the growth-arrested preadipocytes to reentry into postconfluent mitosis. However, HBP1 expression is up-regulated at the end of the MCE to ensure the up-regulation of C/EBPα and the termination of the MCE as well as the onset of terminal differentiation.

Our results demonstrated that F-NLR, a novel inflammation-based grading system, as well as the glasgow prognostic score (GPS), appeared to have value as a promising clinical predictor of the prognosis for the resectable non small cell lung cancer (NSCLC) patients.

(1) FAS can be knocked out via the CRISPR/Cas9 system in porcine early embryonic development. (2) FAS knockout impaired the porcine embryonic development due to the induction of the endoplasmic reticulum stress. (3) FAS knockout induce the endoplasmic reticulum stress response displayed by the spliced XBP1 and phosphorylation of PERK.

Messenger molecules released as a result of beta cell damage triggered by excessive nutrient. These molecules stimulate the pancreatic stem cells to differentiate in vitro to form new beta cells. Thus, they are likely to be potential for diagnosis and treatment of diabetes.

C57BL/6 mice were treated with CpG-ODN 2 hours prior to MI induction, and cardiac function and histology were analyzed 2 weeks after MI. We demonstratged that CpG-ODN preconditioning significantly protects cardiac function against MI by suppressing the energy metabolism of cardiomyocytes and promoting angiogenesis. Our data also indicate that CpG-ODN preconditioning may be useful in MI therapy.

The enhancement of cytotoxic effect of anticancer drugs by MIP-1α neutralizing antibody.

The role of fluid stresses in activating the hepatic stem/progenitor cell regenerative response is not well understood. This study hypothesized that immediate early genes (IEGs) with known links to liver regeneration will be upregulated in liver progenitor cells (LPCs) exposed to in vitro shear stresses on the order of those produced from elevated interstitial flow after partial hepatectomy. Two hours of shear stress exposure at ∼4 dyn/cm² was applied to LPCs embedded individually or as 3D spheroids within a hyaluronic acid/collagen I hydrogel. Four IEGs (CFOS, IP10, MKP1, ALB) and three other regeneration-related genes (WNT, VEGF, EpCAM) were significantly upregulated in LPCs in response to fluid mechanical stress.

Hypoxia differently affects cell survival and pro-apoptotic program in neuroblastoma (NB) cells. RAI plays an important role in hypoxic signaling and the interplay between RAI and HIF-1α may be relevant in the protection of NB cells against hypoxia.

The study provides evidence that miR-206 alleviates the inhibition of activation of hippocampal astrocytes in aged rats induced by sevoflurane by targeting IGT-1 through suppressing the PI3K/AKT/CREB signaling pathway.

We exhibited that inhibition of XIST alleviated neuropathic pain development of CCI rats via upregulating miR-137 and downregulating TNFAIP1. Both in vitro and in vivo assays were carried out to elucidate the mechanisms of XIST/miR-137/TNFAIP1 axis in regulating neuropathic pain development. Our findings indicate that XIST can be identified as a novel therapeutic target for neuropathic pain treatment.

Induction of hyperoxia increases atrial I_kur and I_to currents and thereby causing arrhythmia.

We established a polyvinyl alcohol (PVA) scaffold and a differentiation protocol by adding platelet-rich plasma (PRP) that induces the hADSCs into insulin-producing cells (IPCs). The results of our study for the first time demonstrated that the PVA nanofibrous scaffolds along with the optimized differentiation protocol with PRP can enhance the differentiation of IPCs from hADSCs. In conclusion, this study provides a new approach to the future pancreatic tissue engineering and beta cell replacement therapies for type 1 diabetes mellitus.

NONO is an RNA-binding protein involved in many cellular pathways. Its expression has been found altered in several tumor types and in papillary renal carcinoma, in which an X chromosome inversion generates a NONO-TFE3 fusion protein. We identified a degron motif in NONO protein adding another protein to the long list of FBW7 targets.

Newly identified 59 kDa monomeric quiescence factor (QF) is an α-helical globular protein which inhibits sperm progressive forward motility by decreasing NOS enzyme activity and subsequently reducing intracellular NO-cGMP concentration without modulating intracellular Ca⁺⁺ and cAMP concentration. QF does not damage spermatozoa and its motility inhibitory efficacy is reversible. This study reveals the quiescence mechanism of mature spermatozoa and its energy saving strategy during storage and may help in understanding motility related idiopathic male infertility.

Hindlimb immobilization induced a decline in SCs together with an upregulation of markers of SC activation, suggesting that fusion to existing myofibers takes place during unloading. Muscle recovery induced a significant rise in muscle precursor cells and regeneration events along with reduced SC activation expression markers and a concomitant rise in terminal muscle differentiation expression. These are novel findings of potential applicability for the treatment of disuse muscle atrophy, which is commonly associated with severe chronic and acute conditions.