miRNAs are expressed in many mammalian cells, acting specific roles in regulating gene expression or mediating special mRNAs cleavage by targeting their 3′-untranslated region (3′UTR). Some miRNAs are essential and important for animal development. However, it is still unclear what the relationship is between miR-34c and mammalian spermatogonial stem cells (SSCs). We found that a conserved microRNA-34c through its target-Nanos2, regulating SSCs' differentiation in mouse. Immunohistochemistry analysis of Nanos2 and miR-34c FISH results revealed the opposite expression trends between them. Seven bioinformatics websites and programs predicted that miR-34c has interaction sites in Nanos2's 3′UTR. Dual-luciferase reporter vector and mutated dual-luciferase reporter vector analysis validated that they are interacted. After transfection miR-34c mimics into mouse SSCs, or miR-34c lentiviral vector in vitro co-cultivation with seminiferous tubules, and Western blot analysis demonstrated that miR-34c over-expression could suppress Nanos2 expression in post-transcription level. Our experiments identified that miR-34c may promote meiosis process by interacting with Nanos2 leading up-regulation of Stra8 in mouse spermatogonial stem cells. J. Cell. Biochem. 115: 232–242, 2014. © 2013 Wiley Periodicals, Inc.

miR‐34c Enhances Mouse Spermatogonial Stem Cells Differentiation by Targeting Nanos2

Glycogen synthase kinase (GSK)3β is a multifunctional serine/threonine protein kinase with more than 100 substrates and interacting molecules. GSK3β is normally active in cells and negative regulation of GSK3β activity via phosphorylation of its serine 9 residue is required for most normal cells to maintain homeostasis. Aberrant expression and activity of GSK3β contributes to the pathogenesis and progression of common recalcitrant diseases such as glucose intolerance, neurodegenerative disorders and cancer. Despite recognized roles against several proto-oncoproteins and mediators of the epithelial-mesenchymal transition, deregulated GSK3β also participates in tumor cell survival, evasion of apoptosis, proliferation and invasion, as well as sustaining cancer stemness and inducing therapy resistance. A therapeutic effect from GSK3β inhibition has been demonstrated in 25 different cancer types. Moreover, there is increasing evidence that GSK3β inhibition protects normal cells and tissues from the harmful effects associated with conventional cancer therapies. Here, we review the evidence supporting aberrant GSK3β as a hallmark property of cancer and highlight the beneficial effects of GSK3β inhibition on normal cells and tissues during cancer therapy. The biological rationale for targeting GSK3β in the treatment of cancer is also discussed at length.

Glycogen Synthase Kinase 3β in Cancer Biology and Treatment

Here, we investigated the role of the Wnt/β-catenin signaling pathway in chicken primordial germ cells (PGCs) in vitro. We confirmed the expression of Wnt signaling pathway-related genes and the localization of β-catenin in the nucleus, revealing that this pathway is potentially activated in chicken PGCs. Then, using the single-cell pick-up assay, we examined the proliferative capacity of cultured PGCs in response to Wnt ligands, a β-catenin-mediated Wnt signaling activator (6-bromoindirubin-3′-oxime [BIO]) or inhibitor (JW74), in the presence or absence of basic fibroblast growth factor (bFGF). WNT1, WNT3A, and BIO promoted the proliferation of chicken PGCs similarly to bFGF, whereas JW74 inhibited this proliferation. Meanwhile, such treatments in combination with bFGF did not show a synergistic effect. bFGF treatment could not rescue PGC proliferation in the presence of JW74. In addition, we confirmed the translocation of β-catenin into the nucleus by the addition of bFGF after JW74 treatment. These results indicate that there is signaling crosstalk between FGF and Wnt, and that β-catenin acts on PGC proliferation downstream of bFGF. In conclusion, our study suggests that Wnt signaling enhances the proliferation of chicken PGCs via the stabilization of β-catenin and activation of its downstream genes.

/pdf/wnt-b-catenin-signaling-pathway-activation-is-required-for-3zyi568mxd.pdf

Wnt/β-catenin signaling pathway activation is required for proliferation of chicken primordial germ cells in vitro

Several species belonging to the genus Tabernaemontana have been well researched and utilized for their wide-ranging biological activities A few of the most prominent species include Tabernaemontana divaricata, Tabernaemontana catharinensis, Tabernaemontana crassa, and Tabernaemontana elegans These species and many others within the genus often display pharmacological importance, which is habitually related to their chemical constituents The secondary metabolites within the genus have demonstrated huge medicinal potential for the treatment of infections, pain, injuries, and various diseases Regardless of the indispensable reports and properties displayed by Tabernaemontana spp, there remains a wide variety of plants that are yet to be considered or examined Thus, an additional inclusive study on species within this genus is essential The current review aimed to extensively analyze, collate, and describe an updated report of the current literature related to the major alkaloidal components and biological activities of species within the genus Tabernaemontana

https://www.mdpi.com/2223-7747/10/2/313/pdf

Major Bioactive Alkaloids and Biological Activities of Tabernaemontana Species (Apocynaceae)

6BIO Enhances Oligonucleotide Activity in Cells: A Potential Combinatorial Anti-androgen Receptor Therapy in Prostate Cancer Cells

BACKGROUND: The small molecule 6-bromoindirubin-30-oxime (BIO), a glycogen synthase kinase 3 (GSK3) inhibitor, is a pharmacological agent known to maintain self-renewal in human and mouse embryonic stem cells (ESCs). However, the precise role of GSK3 in immortalized pancreatic mesenchymal stem cells (iPMSCs) growth and survival is not completely understood at present. RESULTS: To determine whether this molecule is involved in controlling the proliferation of iPMSCs, we examined the effect of BIO on iPMSCs. We found that the inactivation of GSK3 by BIO can robustly stimulate iPMSCs proliferation and mass formation as shown by QRT-PCR, western blotting, 5-Bromo-2-deoxyuridine (BrdU) immunostaining assay and tunel assay. However, we did not find the related roles of BIO on β cell differentiation by immunostaining, QRT-PCR assay, glucose-stimulated insulin release and C-peptide content analysis. CONCLUSIONS: These results suggest that BIO plays a key role in the regulation of cell mass proliferation and maintenance of the undifferentiated state of iPMSCs.

/pdf/gsk3-inhibitor-bio-regulates-proliferation-of-immortalized-5bpr3rocjd.pdf

GSK3 inhibitor-BIO regulates proliferation of immortalized pancreatic mesenchymal stem cells (iPMSCs).

Conophylline Promotes the Proliferation of Immortalized Mesenchymal Stem Cells Derived from Fetal Porcine Pancreas (iPMSCs)

The invention discloses an immortalized porcine pancreatic stem cell line and construction and differentiation methods thereof. In the immortalized porcine pancreatic stem cell line, porcine pancreatic stem cells are taken as host cells and are transfected with a pCI-neo-hTERT eukaryotic expression vector, and the human telomerase reverse transcriptase screened by G418 is expressed and has a transformant with multi-directional differentiation potentiality. The cell line also has higher activity after transferring for over 50 generations in vitro, keeps split proliferation, does not generate aging or apoptosis, and is an immortalized cell line. The cell line can be differentiated to form functional islet cell mass after induction, can reduce the blood glucose concentration after being transplanted into a mouse model suffering from diabetes and can maintain a normal blood glucose level within two weeks.

Immortalized porcine pancreatic stem cell line and construction and differentiation methods thereof

Construction and identification of recombinant retroviral vector of human ngn3 gene and its packaging cell line

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GSK3 inhibitor-BIO regulates proliferation of immortalized pancreatic mesenchymal stem cells (iPMSCs).

Conophylline Promotes the Proliferation of Immortalized Mesenchymal Stem Cells Derived from Fetal Porcine Pancreas (iPMSCs)

Immortalized porcine pancreatic stem cell line and construction and differentiation methods thereof

Construction and identification of recombinant retroviral vector of human ngn3 gene and its packaging cell line