Sertoli Cell-Specific Activation of Transforming Growth Factor Beta Receptor 1 Leads to Testicular Granulosa Cell Tumor Formation.

The transforming growth factor β (TGFβ) superfamily, consisting of protein ligands, receptors, and intracellular SMAD transducers, regulates fundamental biological processes and cancer development. Our previous study has shown that sustained activation of TGFβ receptor 1 (TGFBR1) driven by anti-Mullerian hormone receptor type 2 ()-Cre in the mouse testis induces the formation of testicular granulosa cell tumors (TGCTs). As -Cre is expressed in both Sertoli cells and Leydig cells, it remains unclear whether the activation of TGFBR1 in Sertoli cells alone is sufficient to induce TGCT formation.

Role of EZH2 in Uterine Gland Development.

Enhancer of zeste homolog 2 (EZH2) is a core component of polycomb repressive complex 2 that plays a vital role in transcriptional repression of gene expression. Conditional ablation of EZH2 using progesterone receptor ()-Cre in the mouse uterus has uncovered its roles in regulating uterine epithelial cell growth and stratification, suppressing decidual myofibroblast activation, and maintaining normal female fertility. However, it is unclear whether EZH2 plays a role in the development of uterine glands, which are required for pregnancy success.

Transcriptomic Profiling of Gene Expression Associated with Granulosa Cell Tumor Development in a Mouse Model.

Ovarian granulosa cell tumors (GCTs) are rare sex cord-stromal tumors, accounting for ~5% ovarian tumors. The etiology of GCTs remains poorly defined. Genetically engineered mouse models are potentially valuable for understanding the pathogenesis of GCTs.

EZH2 and Endometrial Cancer Development: Insights from a Mouse Model.

Enhancer of zeste homolog 2 (EZH2), a core component of polycomb repressive complex 2, plays an important role in cancer development. As both oncogenic and tumor suppressive functions of EZH2 have been documented in the literature, the objective of this study is to determine the impact of deletion on the development and progression of endometrial cancer induced by inactivation of phosphatase and tensin homolog (), a tumor suppressor gene frequently dysregulated in endometrial cancer patients. To this end, we created mice harboring uterine deletion of both and using Cre recombinase driven by the progesterone receptor () promoter.

Functional similarity between TGF-beta type 2 and type 1 receptors in the female reproductive tract.

Transforming growth factor β (TGFβ) signaling plays critical roles in reproductive development and function. TGFβ ligands signal through the TGFβ receptor type 2 (TGFBR2)/TGFBR1 complex. As TGFBR2 and TGFBR1 form a signaling complex upon ligand stimulation, they are expected to be equally important for propagating TGFβ signaling that elicits cellular responses.

U3 Serine/Threonine Protein Kinase from MDV-1, MDV-2, and HVT Differentially Regulate Viral Gene Expression and Replication.

2 (GaHV-2), commonly known as Marek's disease virus type 1 (MDV-1), is an oncogenic avian alphaherpesvirus, and along with its close relatives- 3 (GaHV-3) or MDV-2 and 1 (MeHV-1) or turkey herpesvirus (HVT)-belongs to the genus. We and others previously showed that MDV-1 U3 protein kinase plays an important role in viral replication and pathogenesis, which could be partially compensated by MDV-2 and HVT U3. In this study, we further studied the differential roles of MDV-1, MDV-2 and HVT U3 in regulating viral gene expression and replication.

Supplementation with beta-1,3-glucan improves productivity, immunity and antioxidative status in transition Holstein cows.

Dairy cows undergo dramatic physiological changes during the transition from late pregnancy to early lactation, which make them vulnerable to metabolic stress and immune dysfunction. The objective of this study was to evaluate the effects of a commercial beta-1,3-glucan product (Aleta™, containing 50% beta-1,3-glucan) on productivity, immunity and antioxidative status in transition cows. Fifty-four multiparous Holstein cows received a control diet or a diet supplemented with 5 or 10 g of beta-1,3-glucan per cow per day from 21 days before expected calving to 21 days after parturition.

New insights into testicular granulosa cell tumors.

Testicular granulosa cell tumors (TGCTs) are rare tumors of sex cord-stromal origin. TGCTs are mostly benign and can be classified into the adult type and the juvenile type. Due to the rarity of clinical cases and limited research efforts, the mechanism underpinning the development of TGCTs remains poorly understood.

Transforming growth factor beta signaling and decidual integrity in mice†.

Transforming growth factor beta (TGFβ) signaling regulates multifaceted reproductive processes. It has been shown that the type 1 receptor of TGFβ (TGFBR1) is indispensable for female reproductive tract development, implantation, placental development, and fertility. However, the role of TGFβ signaling in decidual development and function remains poorly defined.

Effects of beta-1,3-glucan supplementation on concentrations of serum metabolites in transition Holstein cows.

Objectives of this study were to evaluate the alleviating effects of a commercial beta-1,3-glucan product (Aleta, containing 50% beta-1,3-glucan, Kemin Industries) on metabolic stress in transition Holstein cows as reflected by circulating metabolites and enzymes. Fifty-four multiparous Holstein cows were randomly allocated to three groups with 18 cows each. Cows in each group received a commercial basal diet or the basal diet supplemented with Aleta calculated to supply 5 or 10 g of Aleta per cow per day.

Effect of Pd/Ce loading on the performance of Pd-Ce/γ-AlO catalysts for toluene abatement.

A single metal Pd/γ-AlO catalyst and a bimetallic Pd-Ce/γ-AlO catalyst were prepared by the equal-volume impregnation method to investigate the effect of CeO loading on the catalytic oxidation of toluene. The specific surface area, surface morphology, and redox performance of the catalyst were characterized by N desorption, scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), H-TPR, O-TPD, and electron paramagnetic resonance (EPR). The results showed that bimetal catalysts loaded CeO had smaller nano-PdO particles than those of the Pd/γ-AlO catalyst.

Enhancer of Zeste 2 Polycomb Repressive Complex 2 Subunit Is Required for Uterine Epithelial Integrity.

Normal proliferation and differentiation of uterine epithelial cells are critical for uterine development and function. Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), a core component of polycomb repressive complexes 2, possesses histone methyltransferase activity that catalyzes the trimethylation of lysine 27 of histone H3. EZH2 has been involved in epithelial-mesenchymal transition, a key event in development and carcinogenesis.

Glandular defects in the mouse uterus with sustained activation of TGF-beta signaling is associated with altered differentiation of endometrial stromal cells and formation of stromal compartment.

Uterine gland development, also known as adenogenesis, is a key uterine morphogenic process indispensable for normal uterine function and fertility. Our earlier studies have reported that overactivation of TGFB receptor 1 (TGFBR1) in the mouse uterus using progesterone receptor (Pgr)-Cre recombinase causes female infertility, defective decidualization, and reduced uterine gland formation, a developmental milestone of postnatal uterus. To understand mechanisms that underpin the disrupted uterine gland formation in mice with sustained activation of TGFBR1, we raised the question of whether early postnatal adenogenesis was compromised in these mice.

A novel mouse model of testicular granulosa cell tumors.

Study Question: What is the role of dysregulated transforming growth factor beta (TGFB) signaling in the development of sex cord-stromal tumors in the testis?

Summary Answer: Overactivation of TGFB signaling results in the development of testicular tumors resembling granulosa cell tumors (GrCTs).

What Is Known Already: In an earlier study, we demonstrated that constitutively active TGFB receptor 1 (TGFBR1) in ovarian somatic cells promotes the development of ovarian GrCTs. However, the consequence of dysregulation of TGFB signaling in the pathobiology of the testis, remains poorly defined.

Disruption of postnatal folliculogenesis and development of ovarian tumor in a mouse model with aberrant transforming growth factor beta signaling.

Background: Transforming growth factor beta (TGFB) superfamily signaling is implicated in the development of sex cord-stromal tumors, a category of poorly defined gonadal tumors. The aim of this study was to determine potential effects of dysregulated TGFB signaling in the ovary using Cre recombinase driven by growth differentiation factor 9 (Gdf9) promoter known to be expressed in oocytes.

Methods: A mouse model containing constitutively active TGFBR1 (TGFBR1) using Gdf9-iCre (termed TGFBR1-CA) was generated.

TGFβ superfamily signaling and uterine decidualization.

Decidualization is an intricate biological process where extensive morphological, functional, and genetic changes take place in endometrial stromal cells to support the development of an implanting blastocyst. Deficiencies in decidualization are associated with pregnancy complications and reproductive diseases. Decidualization is coordinately regulated by steroid hormones, growth factors, and molecular and epigenetic mechanisms.

Conditional abrogation of transforming growth factor-β receptor 1 in PTEN-inactivated endometrium promotes endometrial cancer progression in mice.

Although a putative role for transforming growth factor-β (TGFB) signalling in the pathogenesis of human endometrial cancer has long been proposed, the precise function of TGFB signalling in the development and progression of endometrial cancer remains elusive. Depletion of phosphatase and tensin homologue (PTEN) in the mouse uterus causes endometrial cancer. To identify the potential role of TGFB signalling in endometrial cancer, we simultaneously deleted TGFB receptor 1 (Tgfbr1) and Pten in the mouse uterus by using Cre-recombinase driven by the progesterone receptor (termed Pten ;Tgfbr1 ).

SMAD3 Activation: A Converging Point of Dysregulated TGF-Beta Superfamily Signaling and Genetic Aberrations in Granulosa Cell Tumor Development?

Ovarian granulosa cell tumors (GCTs) are rare gynecologic tumors in women. Due to the rarity and limited research efforts invested, the etiology of GCTs remains poorly defined. A landmark study has discovered the mutation of forkhead box L2 (FOXL2) as a genetic hallmark of adult GCTs in the human.

Constitutively active transforming growth factor β receptor 1 in the mouse ovary promotes tumorigenesis.

Despite the well-established tumor suppressive role of TGFβ proteins, depletion of key TGFβ signaling components in the mouse ovary does not induce a growth advantage. To define the role of TGFβ signaling in ovarian tumorigenesis, we created a mouse model expressing a constitutively active TGFβ receptor 1 (TGFBR1) in ovarian somatic cells using conditional gain-of-function approach. Remarkably, these mice developed ovarian sex cord-stromal tumors with complete penetrance, leading to reproductive failure and mortality.

[Database Establishing and Data Mining of Pulmonary Diseases Based on Clinical Works by Modern Famous Veteran Doctors of Chinese Medicine].

Objective: To explore syndrome and treatment laws for treating diseases of the pulmonary system by establishing database based on clinical works by modern famous veteran doctors of Chinese medicine (CM).

Methods: Clinical experience and literature of medical records in clinical works by modern famous veteran doctors of CM were taken as data source. Database was established by fields and program design.

Beyond Benford's Law: Distinguishing Noise from Chaos.

Determinism and randomness are two inherent aspects of all physical processes. Time series from chaotic systems share several features identical with those generated from stochastic processes, which makes them almost undistinguishable. In this paper, a new method based on Benford's law is designed in order to distinguish noise from chaos by only information from the first digit of considered series.

Inhibitory SMADs: potential regulators of ovarian function.

Transforming growth factor beta (TGFB) superfamily signaling regulates essential reproductive functions. Dysregulation of TGFB signaling results in cellular and molecular deficiencies in the ovary, leading to reproductive diseases and cancer development. SMAD proteins are canonical TGFB signaling components consisting of receptor-regulated SMADs (SMAD1/2/3/5/9), a common SMAD (SMAD4), and inhibitory SMADs (SMAD6/7).