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Background: The cell-cycle regulator Cyclin D1 is expressed in embryonic retinal progenitor cells (RPCs) and regulates their cell-cycle rate and neurogenic output. We report here that Cyclin D1 also has important functions in postnatal retinal histogenesis., Results: The initial production of Müller glia and bipolar cells was enhanced in Cyclin D1 knockout (Ccnd1(-/-) ) retinas. Despite a steeper than normal rate of depletion of the RPC population at embryonic ages, postnatal Ccnd1(-/-) retinas exhibited an extended window of proliferation, neurogenesis, and gliogenesis. Cyclin D3, normally confined to Müller glia, was prematurely expressed in Ccnd1(-/-) RPCs. However, Cyclin D3 did not compensate for Cyclin D1 in regulating cell-cycle kinetics or neurogenic output., Conclusions: The data presented in this study along with our previous finding that Cyclin D2 was unable to completely compensate for the absence of Cyclin D1 indicate that Cyclin D1 regulates retinal histogenesis in ways not shared by the other D-cyclins., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Maintaining the correct balance of proliferation versus differentiation in retinal progenitor cells (RPCs) is essential for proper development of the retina. The cell cycle regulator cyclin D1 is expressed in RPCs, and mice with a targeted null allele at the cyclin D1 locus (Ccnd1-/ -) have microphthalmia and hypocellular retinas, the latter phenotype attributed to reduced RPC proliferation and increased photoreceptor cell death during the postnatal period. How cyclin D1 influences RPC behavior, especially during the embryonic period, is unclear. Results: In this study, we show that embryonic RPCs lacking cyclin D1 progress through the cell cycle at a slower rate and exit the cell cycle at a faster rate. Consistent with enhanced cell cycle exit, the relative proportions of cell types born in the embryonic period, such as retinal ganglion cells and photoreceptor cells, are increased. Unexpectedly, cyclin D1 deficiency decreases the proportions of other early born retinal neurons, namely horizontal cells and specific amacrine cell types. We also found that the laminar positioning of horizontal cells and other cell types is altered in the absence of cyclin D1. Genetically replacing cyclin D1 with cyclin D2 is not efficient at correcting the phenotypes due to the cyclin D1 deficiency, which suggests the D-cyclins are not fully redundant. Replacement with cyclin E or inactivation of cyclin-dependent kinase inhibitor p27Kip1 restores the balance of RPCs and retinal cell types to more normal distributions, which suggests that regulation of the retinoblastoma pathway is an important function for cyclin D1 during embryonic retinal development. Conclusion: Our findings show that cyclin D1 has important roles in RPC cell cycle regulation and retinal histogenesis. The reduction in the RPC population due to a longer cell cycle time and to an enhanced rate of cell cycle exit are likely to be the primary factors driving retinal hypocellularity and altered output of precursor populations in the embryonic Ccnd1-/- retina. [ABSTRACT FROM AUTHOR]

Hypericum roeperianum is a medicinal spice traditionally used in West Africa to treat female sterility, fungal infections, and cancer. It has previously been reported that H. roeperianum exhibits cytotoxic potential by reducing the viability of cancer cells involving multidrug-resistant phenotypes, but its underlying molecular mechanism remains unknown. The mechanistic involvement of H. roeperianum methanolic crude extract (HRC) in attenuating breast cancer progression by exploring the effects on mitochondrial apoptosis and epithelial-mesenchymal transition (EMT) was investigated. In the present study, we examined the anticancer properties of HRC through MTT assay, colony formation, wound healing assay, spheroid formation, DNA fragmentation and flow cytometry for cell cycle arrest, apoptosis (Annexin V/PI staining) and mitochondrial membrane potential (MMP) (JC-1) detection. In addition, western blot analysis of various proteins and quantitative real time PCR of various genes involved in apoptosis, EMT and the PI3K/Akt/mToR signal transduction pathway were performed. This study revealed that HRC treatment significantly decreased breast cancer cell viability, colony forming efficiency and reduced the ability of cell migration and spheroid formation. HRC also induced apoptosis in MDA-MB-231 and MCF-7 via promoting G0/G1 cell cycle arrest, disruption of mitochondrial membrane potential and induction of DNA damage. The crude extract induced apoptosis by activating the intrinsic pathway with a stronger effect that relies on the combined potency of associated molecular markers including Bax, Bad, Bcl-2, cytochrome C, caspase-9, and cleaved-PARP. It was also found that HRC regulates the PI3K/Akt/mToR pathway. In addition, HRC inhibited EMT by expressional alteration of Vimentin and E-cadherin, as well as the regulatory transcription factors such as Snail and Slug. The in vitro findings reflected similar mechanistic approach in 4T1 cell induced syngeneic mice model, indicating the reduction of tumor volume along with the significant expressional alteration of EMT and apoptotic markers. Taken together the findings concluded that H. roeperianum is a potential source of cytotoxic phytochemicals that exhibit abortifacient effect on breast cancer, both in vitro and in vivo , thus could further be utilized in breast cancer therapy. [Display omitted] • The anticancer mechanism of action of Hypericum roeperianum crude extract (HRC) was evaluated. • HRC also induced apoptosis in MDA-MB-231 and MCF-7. • HRC causes G0/G1 cell cycle arrest, disruption of mitochondrial membrane potential and DNA damage. • HRC inhibited the epithelial-mesenchymal transition. [ABSTRACT FROM AUTHOR]

[Display omitted] • Dual fluorogenic core of Rhodamine appended chromone Schiff base (RFC) is spectroscopically characterised. • RFC is an efficient sensor to Fe3+, Al3+, Cr3+ at trace level. • LODs are 0.093 μM (Fe3+), 0.11 μM (Al3+) and 0.10 μM (Cr3+) much below the WHO recommended data. • RFC has high anticancer activity to breast cancer MCF-7 cells and IC 50 is 2.53 µM. • RFC shows high growth inhibition efficiency, wound healing capacity and an apoptotic marker. Strategic design of fluorescent probe for the recognition of ions/molecules at very low concentration by fluorescence sensing is one of the stimulating current research topics with reference to health and sustainability. Towards this objective, Rhodamine based chemosensors are playing extraordinary protagonist. In this work, a Rhodamine appended chromone Schiff base (RFC), with two fluorogenic motifs, has been characterized through various spectroscopic techniques. The probe exhibits efficient sensitivity towards Analytical Group IIIA ions (Al3+, Cr3+ and Fe3+) in existence of other competitive analytes. The fluorescent intensity is enhanced by 350 fold (Fe3+), 250 fold (Al3+) and 220 fold (Cr3+), respectively in methanol-water (99:1,v/v; HEPES buffer, pH, 7.2) medium. The limits of detection (LOD) (3σ/M method; σ = standard deviation; M = slope) are 0.0051 ppm (Fe3+), 0.0029 ppm (Al3+) and 0.0052 ppm (Cr3+); which are impressive and much below the WHO recommended data. In addition to this, the compound has been utilized for cell imaging in presence of these three cations. The action of probe on MCF-7 (human breast cancer) cell lines demonstrates IC 50 , 2.53 µM that is far better than activity against WI-38 (normal cell line) (IC 50 , 393.7 µM). The drug (RFC) minimizes the cellular proliferation and has significant wound healing capacity of the infected tissue with MCF-7 cells. The probe shows significant nuclear fragmentation with increase in the expression of apoptotic markers. Growth inhibition analysis in 3D tumor spheroid model showed the inhibition of breast cancer MCF-7 cells. [ABSTRACT FROM AUTHOR]