Stage-specific regulation of undifferentiated spermatogonia by AKT1S1-mediated AKT-mTORC1 signaling during mouse spermatogenesis.

Undifferentiated spermatogonia are composed of a heterogeneous cell population including spermatogonial stem cells (SSCs). Molecular mechanisms underlying the regulation of various spermatogonial cohorts during their self-renewal and differentiation are largely unclear. Here we show that AKT1S1, an AKT substrate and inhibitor of mTORC1, regulates the homeostasis of undifferentiated spermatogonia.

Distinctive molecular features of regenerative stem cells in the damaged male germline.

Maintenance of male fertility requires spermatogonial stem cells (SSCs) that self-renew and generate differentiating germ cells for production of spermatozoa. Germline cells are sensitive to genotoxic drugs and patients receiving chemotherapy can become infertile. SSCs surviving treatment mediate germline recovery but pathways driving SSC regenerative responses remain poorly understood.

rescue immature oocytes - a literature review.

Immature oocytes retrieved from fertilization (IVF) and clinical maturation (IVM) is a common problem, especially in patients with advanced age, poor ovarian response (POR), or polycystic ovary syndrome (PCOS). Considering there is no common name to describe this group of oocytes, we suggest naming all of immature oocytes retrieved from IVF and clinical IVM cycles as 'Medical Unusable Oocytes' (MUO) as none of them will be used for subsequent treatment and will eventually be discarded. Scientists attempt to improve the clinical utilization rate of MUO instead of discarding them.

Disabled-2: a positive regulator of the early differentiation of myoblasts.

Dab2 is an adaptor protein and a tumor suppressor. Our previous study has found that Dab2 was expressed in early differentiating skeletal muscles in mouse embryos. In this study, we determined the role of Dab2 in the skeletal muscle differentiation using C2C12 myoblasts in vitro and Xenopus laevis embryos in vivo.

MicroRNA-19a-PTEN Axis Is Involved in the Developmental Decline of Axon Regenerative Capacity in Retinal Ganglion Cells.

Irreversible blindness from glaucoma and optic neuropathies is attributed to retinal ganglion cells (RGCs) losing the ability to regenerate axons. While several transcription factors and proteins have demonstrated enhancement of axon regeneration after optic nerve injury, mechanisms contributing to the age-related decline in axon regenerative capacity remain elusive. In this study, we show that microRNAs are differentially expressed during RGC development and identify microRNA-19a (miR-19a) as a heterochronic marker; developmental decline of miR-19a relieves suppression of phosphatase and tensin homolog (PTEN), a key regulator of axon regeneration, and serves as a temporal indicator of decreasing axon regenerative capacity.

Revealing cellular and molecular transitions in neonatal germ cell differentiation using single cell RNA sequencing.

Neonatal germ cell development provides the foundation of spermatogenesis. However, a systematic understanding of this process is still limited. To resolve cellular and molecular heterogeneity in this process, we profiled single cell transcriptomes of undifferentiated germ cells from neonatal mouse testes and employed unbiased clustering and pseudotime ordering analysis to assign cells to distinct cell states in the developmental continuum.

Yin Yang 1-mediated epigenetic silencing of tumour-suppressive microRNAs activates nuclear factor-κB in hepatocellular carcinoma.

Enhancer of zeste homolog 2 (EZH2) catalyses histone H3 lysine 27 trimethylation (H3K27me3) to silence tumour-suppressor genes in hepatocellular carcinoma (HCC) but the process of locus-specific recruitment remains elusive. Here we investigated the transcription factors involved and the molecular consequences in HCC development. The genome-wide distribution of H3K27me3 was determined by chromatin immunoprecipitation coupled with high-throughput sequencing or promoter array analyses in HCC cells from hepatitis B virus (HBV) X protein transgenic mouse and human cell models.

Molecular mechanisms of regulation and action of microRNA-199a in testicular germ cell tumor and glioblastomas.

MicroRNA-199a (miRNA-199a) has been shown to have comprehensive functions and behave differently in different systems and diseases. It is encoded by two loci in the human genome, miR-199a-1 in chromosome 19 and miR-199a-2 in chromosome 1. Both loci give rise to the same miRNAs (miR-199a-5p and miR-199a-3p).

Putative tumour-suppressor gene DAB2 is frequently down regulated by promoter hypermethylation in nasopharyngeal carcinoma.

Background: Human disabled-2 (DAB2), is a multi-function signalling molecule that it is frequently down-regulated in human cancers. We aimed to investigate the possible tumour suppressor effect of DAB2 in nasopharyngeal carcinoma (NPC).

Methods: We studied the expression of DAB2 in NPC cell lines, xenografts and primary tumour samples.

Differential bortezomib sensitivity in head and neck cancer lines corresponds to proteasome, nuclear factor-kappaB and activator protein-1 related mechanisms.

Head and neck squamous cell carcinomas (HNSCC) exhibit constitutive activation of transcription factors nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1), which are modulated by the proteasome and promote resistance to cell death. HNSCC show variable sensitivity to the proteasome inhibitor bortezomib in vitro as well as in murine xenografts and patient tumors in vivo, and the mechanisms are not well understood. To address this question, the sensitivities of nine HNSCC cell lines to bortezomib were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, and the potential relationship between the sensitivity and bortezomib effects on biological processes was examined in HNSCC lines of differential bortezomib sensitivity.

A signal network involving coactivated NF-kappaB and STAT3 and altered p53 modulates BAX/BCL-XL expression and promotes cell survival of head and neck squamous cell carcinomas.

Abrogation of apoptosis to sustain cell survival is an essential step in development of cancer. Aberrant activation of signal transcription factors NF-kappaB or STAT3, alterations in p53 status, or BCL/BAX family expression have each been reported to affect cell survival in cancer, including head and neck squamous cell carcinomas (HNSCC). However, molecular targeting of these alterations individually has yielded disappointing results.

A novel nuclear factor-kappaB gene signature is differentially expressed in head and neck squamous cell carcinomas in association with TP53 status.

Purpose: To determine if gene signatures differentially expressed in head and neck squamous cell carcinomas (HNSCC) are related to alterations in transcription factors nuclear factor-kappaB (NF-kappaB) and TP53 previously associated with decreased cell death, response to therapy, and worse prognosis.

Experimental Design: Unique gene signatures expressed by HNSCC lines were identified by cDNA microarray, principal components, and cluster analyses and validated by quantitative reverse transcription-PCR (RT-PCR) and in situ hybridization. Bioinformatic analysis of the promoters and ontogeny of these clustered genes was done.

Effects of preoperative therapeutic play on outcomes of school-age children undergoing day surgery.

The purpose of this study was to examine the effects of therapeutic play on outcomes of children undergoing day surgery. Two hundred and three children admitted for day surgery were invited to participate in a randomized controlled trial. The experimental group received therapeutic play; the control group received routine information preparation.

Psychoeducational preparation of children for surgery: the importance of parental involvement.

Objective: To examine the effects of therapeutic play intervention on outcomes of children undergoing day surgery, and to highlight the importance of parental involvement in the psychoeducational preparation of children for surgery.

Methods: A randomized controlled trial, two group pre-test and repeated post-test, between subjects design was employed. Hong Kong Chinese children (7-12 years of age; n=203) admitted for elective surgery in a day surgery unit, along with their parents during a 13-month period, were invited to participate in the study.

Application of transcriptional and biological network analyses in mouse germ-cell transcriptomes.

Serial analysis of gene expression (SAGE) provides a global analysis platform for profiling mRNA populations present in cells of interest without the constraint of gene selection and the ambiguous nature of data obtained. However, most of the reports on SAGE and germ cell development are limited to descriptive analyses. Here, we report a series of bioinformatic analyses using recently published SAGE data on the transcriptome of mouse type A spermatogonia (Spga), pachytene spermatocytes (Spcy), and round spermatids (Sptd).

Epigenetic modification of SOCS-1 differentially regulates STAT3 activation in response to interleukin-6 receptor and epidermal growth factor receptor signaling through JAK and/or MEK in head and neck squamous cell carcinomas.

Signal transducer and activator of transcription 3 (STAT3) has been reported to be activated by interleukin-6 receptor (IL-6R) or epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinomas (HNSCC), which may have important implications for responsiveness to therapeutics targeted at EGFR, IL-6R, or intermediary kinases. Suppressor of cytokine signaling-1 (SOCS-1) has been implicated recently in the negative regulation of IL-6R/Janus-activated kinase (JAK)-mediated activation of STAT3, suggesting that SOCS-1 could affect alternative activation of STAT3 by EGFR, IL-6R, and associated kinases. We investigated whether epigenetic modification of SOCS-1 affects STAT3 activation in response to IL-6R-, EGFR-, JAK-, or mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK)-mediated signal activation.

Hepatocyte growth factor/scatter factor differentially regulates expression of proangiogenic factors through Egr-1 in head and neck squamous cell carcinoma.

Hepatocyte growth factor/scatter factor (HGF) and the angiogenesis factors platelet-derived growth factors (PDGF), vascular endothelial growth factor (VEGF), and interleukin-8 (IL-8) are found in elevated concentrations in serum or tumor tissue of patients with head and neck squamous cell carcinomas (HNSCC), suggesting these factors may be coregulated. A cDNA microarray analysis for HGF-inducible genes revealed that HGF also modulates PDGFA expression, a gene recently shown to be inducible by the transcription factor, early growth response-1 (Egr-1). In the present study, we investigated the potential role of HGF-induced Egr-1 in expression of PDGF, VEGF, and IL-8.

Nuclear factor-kappaB is an important modulator of the altered gene expression profile and malignant phenotype in squamous cell carcinoma.

We reported previously that transcription factor nuclear factor (NF)-kappaB is constitutively activated in human and murine squamous cell carcinomas (SCCs). The role of NF-kappaB in the cumulative changes in gene expression with transformation and progression of the murine SCC Pam 212 and after switching off NF-kappaB by a dominant negative inhibitor kappaB mutant (IkappaBalphaM) was explored by profiling with a 15,000-element cDNA micoarrray. Remarkably, NF-kappaB modulated the expression of >60% of the 308 genes differentially expressed between normal keratinocytes and metastatic SCCs.

Metastatic squamous cell carcinoma cells that overexpress c-Met exhibit enhanced angiogenesis factor expression, scattering and metastasis in response to hepatocyte growth factor.

We previously performed gene expression profiling in a multistep squamous cell carcinoma (SCC) progression model, and identified growth-regulated oncogene-1 (Gro-1/KC) as a factor that contributes to enhanced angiogenesis, tumorigenesis and metastasis. In the present study, we explored molecular pathways coactivated with Gro-1/KC, and identified a transcript that encodes c-Met, the receptor for hepatocyte growth factor/scatter factor (HGF). Northern, Western blot, and immunohistochemical analyses confirm that expression of c-Met mRNA and protein is increased with SCC progression.

Medicinal mushroom extracts inhibit ras-induced cell transformation and the inhibitory effect requires the presence of normal cells.

Previously, we developed a simple Rat 6 (R6) cell system by which the inhibitory effects of non-cytotoxic chemicals can be assessed by focus formation assay upon transfection of ras oncogene to the host cells. Using this system, two well studied medicinal mushrooms Ganoderma lucidum and Tricholoma lobayense with anticancer potential were examined for their possible advert effects on cell transformation induced by ras oncogene. Results indicated that both species of mushrooms yielded strong inhibitory effects on ras-induced cell transformation.

Hypermethylation of the tumor suppressor gene RASSFIA and frequent concomitant loss of heterozygosity at 3p21 in cervical cancers.

Loss of heterozygosity (LOH) at chromosome 3p21 is frequent in cervical cancers. The candidate tumor suppressor gene, RASSF1A located at 3p21.3, is found to be inactivated in several major human cancers, implicating its significance in carcinogenesis.

Hypermethylation of multiple genes in tumor tissues and voided urine in urinary bladder cancer patients.

Purpose: We aimed to investigate the methylation pattern in bladder cancer and assess the diagnostic potential of such epigenetic changes in urine.

Experimental Design: The methylation status of 7 genes (RARbeta, DAPK, E-cadherin, p16, p15, GSTP1, and MGMT) in 98 cases of bladder transitional cell carcinoma and 4 cases of carcinoma in situ was analyzed by methylation-specific PCR. Twenty-two cases had paired voided urine samples for analysis.