Anti-Müllerian hormone signaling in the ovary involves stromal fibroblasts: a study in humans and mice provides novel insights into the role of ovarian stroma.

Study Question: What is the involvement of ovarian stroma in the anti-Müllerian hormone (AMH) signaling pathway and which stromal cells are involved?

Summary Answer: Mouse and human ovaries show high expression of AMH receptor II (AMHR2) in the stromal fibroblasts surrounding the follicles and activation of the post-AMHR2 pathway by recombinant AMH was evidenced by increased phosphorylation of SMAD1,5 and 9, increased expression AMHR2 and upregulation of αSMA, suggesting fibroblast activation to initiate myofibroblast differentiation.

What Is Known Already: AMH secreted by small growing follicles, regulates ovarian activity. It suppresses initial primordial follicle (PMF) recruitment and FSH-dependent growth.

Short-chain fatty acids in cancer pathogenesis.

Cancer is a multi-step process that can be viewed as a cellular and immunological shift away from homeostasis in response to selected infectious agents, mutations, diet, and environmental carcinogens. Homeostasis, which contributes importantly to the definition of "health," is maintained, in part by the production of short-chain fatty acids (SCFAs), which are metabolites of specific gut bacteria. Alteration in the composition of gut bacteria, or dysbiosis, is often a major risk factor for some two dozen tumor types.

Dual suppression of follicle activation pathways completely prevents the cyclophosphamide-induced loss of ovarian reserve.

Study Question: To what extent and how does combined administration of the follicle activation pathway suppressive agents temsirolimus (Tem) and c-terminus recombinant anti-Müllerian hormone (rAMH) protect against chemotherapy-induced ovarian reserve loss?

Summary Answer: Combined administration of Tem and rAMH completely prevents cyclophosphamide (Cy)-induced follicle depletion and protects the ovarian reserve in mice, primarily via primordial follicle (PMF) suppression of activation and to a lesser degree by reducing apoptosis.

What Is Known Already: There is conflicting evidence regarding the contributory roles of apoptosis and follicle activation in chemotherapy-induced PMF loss. Tem, a mammalian target of rapamycin (mTOR) inhibitor, reduces activity of the phosphoinositide 3-kinases-phosphatase and tensin homolog (PI3K-PTEN) pathway which provides intrinsic regulation of PMF activation.

Hepatitis B x (HBx) as a Component of a Functional Cure for Chronic Hepatitis B.

Patients who are carriers of the hepatitis B virus (HBV) are at high risk of chronic liver disease (CLD) which proceeds from hepatitis, to fibrosis, cirrhosis and to hepatocellular carcinoma (HCC). The hepatitis B-encoded X antigen, HBx, promotes virus gene expression and replication, protects infected hepatocytes from immunological destruction, and promotes the development of CLD and HCC. For virus replication, HBx regulates covalently closed circular (ccc) HBV DNA transcription, while for CLD, HBx triggers cellular oxidative stress, in part, by triggering mitochondrial damage that stimulates innate immunity.

Ultrafast Dynamics Experienced by Carbon Dioxide Diffusing through Polymer Matrices.

Fourier transform infrared, pump-probe polarization anisotropy, and two-dimensional infrared spectroscopies were used to study the steady-state and time-dependent behavior of carbon dioxide dissolved in three different polymer systems. Gas reorientation dynamics in poly(methyl methacrylate), poly(methyl acrylate), and poly(dimethylsiloxane) were sensitive to the nature of chemical interactions between the gas and polymer, as well as whether the polymer was in a glassy or rubbery phase. The homogeneous dynamics experienced by the asymmetric stretching vibration were found to be fastest for rubbery polymers with weak, nonspecific gas-polymer interactions.

Opal-based terahertz optical elements fabricated by self-assembly of porous SiO nanoparticles.

In this paper, we study artificial opals as a promising material platform for terahertz (THz) optics. Materials were synthesized using self-assembly of porous SiO nanoparticles and annealing at different temperatures to further tune their optical properties. Two distinct approaches for the fabrication of bulk THz optics from these novel materials were considered.

Ovaries of patients recently treated with alkylating agent chemotherapy indicate the presence of acute follicle activation, elucidating its role among other proposed mechanisms of follicle loss.

Objective: To investigate mechanisms of primordial follicle (PMF) loss in vivo in human ovaries shortly after alkylating agent (AA) chemotherapy.

Design: Cohort study.

Setting: Tertiary university medical center.

Pharmacological administration of recombinant human AMH rescues ovarian reserve and preserves fertility in a mouse model of chemotherapy, without interfering with anti-tumoural effects.

Purpose: To determine whether pharmacological administration of recombinant human anti-Mullerian hormone (rAMH) protects the ovarian reserve and preserves fertility without interfering with anti-tumoural cytotoxic action of chemotherapy.

Methods: Intraperitoneal delivery of rAMH and ovarian post-receptor activity were assessed with immunohistochemistry and western blot. Differential follicle counts and reproductive outcomes were assessed after cyclophosphamide (Cy) administration, with/without concurrent administration of rAMH.

Follicle activation is a significant and immediate cause of follicle loss after ovarian tissue transplantation.

Purpose: Extensive follicle loss has been demonstrated in ovarian grafts post transplantation, reducing their productivity and lifespan. Several mechanisms for this loss have been proposed, and this study aims to clarify when and how the massive follicle loss associated with transplantation of ovarian tissue graft occurs. An understanding of the mechanisms of follicle loss will pinpoint potential new targets for optimization and improvement of this important fertility preservation technique.

Enhanced vibrational solvatochromism and spectral diffusion by electron rich substituents on small molecule silanes.

Fourier transform infrared and two-dimensional IR (2D-IR) spectroscopies were applied to two different silanes in three different solvents. The selected solutes exhibit different degrees of vibrational solvatochromism for the Si-H vibration. Density functional theory calculations confirm that this difference in sensitivity is the result of higher mode polarization with more electron withdrawing ligands.

Correlating solvent dynamics and chemical reaction rates using binary solvent mixtures and two-dimensional infrared spectroscopy.

Two-dimensional infrared (2D-IR) spectroscopy was performed on Vaska's complex (VC) and its oxygen adduct (V C-O2) in binary solvent mixtures of chloroform or benzyl alcohol in d6-benzene. The second order rate constants for oxygenation were also measured in these solvent mixtures. The rate constant in chloroform mixtures is linear with mole fraction within the error of the measurements but changes nonlinearly in benzyl alcohol mixtures, displaying a preference for the alcohol over benzene.

Simple fully reflective method of scatter reduction in 2D-IR spectroscopy.

A fully reflective two-dimensional IR (2D-IR) setup is described that enables efficient cancellation of scattered light from multiple pulses in the phase-matched direction. The local oscillator pulse and the pulse that stimulates the vibrational echo signal are synchronously modulated (or fibrillated) in time maintaining their phase relationships with the echo wavepacket. The modification is cost-effective and can be easily implemented on existing 2D-IR instruments, and it avoids the addition of dispersive elements into the beam paths.

Practical Applications of in Vivo and ex Vivo MRI in Toxicologic Pathology Using a Novel High-performance Compact MRI System.

Magnetic resonance imaging (MRI) is widely used in preclinical research and drug development and is a powerful noninvasive method for assessment of phenotypes and therapeutic efficacy in murine models of disease. In vivo MRI provides an opportunity for longitudinal evaluation of tissue changes and phenotypic expression in experimental animal models. Ex vivo MRI of fixed samples permits a thorough examination of multiple digital slices while leaving the specimen intact for subsequent conventional hematoxylin and eosin (H&E) histology.

Halofuginone - the multifaceted molecule.

Halofuginone is an analog of febrifugine-an alkaloid originally isolated from the plant Dichroa febrifuga. During recent years, halofuginone has attracted much attention because of its wide range of beneficial biological activities, which encompass malaria, cancer, and fibrosis-related and autoimmune diseases. At present two modes of halofuginone actions have been described: (1) Inhibition of Smad3 phosphorylation downstream of the TGFβ signaling pathway results in inhibition of fibroblasts-to-myofibroblasts transition and fibrosis.

The involvement of collagen triple helix repeat containing 1 in muscular dystrophies.

Fibrosis is the main complication of muscular dystrophies. We identified collagen triple helix repeat containing 1 (Cthrc1) in skeletal and cardiac muscles of mice, representing Duchenne and congenital muscle dystrophies (DMD and CMD, respectively), and dysferlinopathy. In all of the mice, Cthrc1 was associated with high collagen type I levels; no Cthrc1 or collagen was observed in muscles of control mice.

Involvement of host stroma cells and tissue fibrosis in pancreatic tumor development in transgenic mice.

Introduction: Stroma cells and extracellular matrix (ECM) components provide the pivotal microenvironment for tumor development. The study aimed to evaluate the importance of the pancreatic stroma for tumor development.

Methods: Pancreatic tumor cells were implanted subcutaneously into green fluorescent protein transgenic mice, and stroma cells invading the tumors were identified through immunohistochemistry.

Infrared multiphoton dissociation spectroscopy study of protonated p-aminobenzoic acid: does electrospray ionization afford the amino- or carboxy-protonated ion?

Infrared multiphoton dissociation spectra of protonated p-aminobenzoic acid generated by electrospray ionization (ESI) from aqueous methanol and acetonitrile solutions were recorded in the gas phase from 2800-4000 cm(-1). The O-protonated ion is more stable than the N-protonated structure in the gas phase, whereas the opposite is true in both solutions. When CH(3)OH/H(2)O was used as the ESI solvent, only the O-protonated ion was observed.

Keloid histopathology after intralesional cryosurgery treatment.

Background: Keloid presents a great healthcare challenge. The patients suffer from aesthetic disfiguration and occasionally from pruritus, pain and discomfort. Although various treatments are recommended, a single, highly effective treatment represents a great clinical need.

Inhibition of pancreatic stellate cell activation by halofuginone prevents pancreatic xenograft tumor development.

Objectives: Most solid tumors consist of neoplastic and nonneoplastic cells and extracellular matrix components. In the pancreas, activated stellate cells (PSCs) are the source of the extracellular matrix proteins. We evaluated the significance of PSC activation in tumor establishment and development in mouse xenografts.

Rage attacks and aggressive symptoms in Japanese adolescents with tourette syndrome.

Objective: This study was conducted to explore possible causes of rage attacks as well as clinically significant aggressive symptoms in Japanese adolescents with Tourette syndrome (TS).

Methods: The subjects included 29 adolescents (23 males, 6 females; mean age: 13.5+/-3.

Selective attentional bias related to the noticeability aspect of anxiety symptoms in generalized social phobia.

Persons with generalized social phobia were compared to nonanxious controls using the modified Stroop test of attentional biases and self-report questionnaires. Results indicated that participants with social phobia showed attentional biases to socially threatening words such as those describing negative evaluation (e.g.

The new anti-actin agent dihydrohalichondramide reveals fenestrae-forming centers in hepatic endothelial cells.

Background: Liver sinusoidal endothelial cells (LSECs) react to different anti-actin agents by increasing their number of fenestrae. A new structure related to fenestrae formation could be observed when LSECs were treated with misakinolide. In this study, we investigated the effects of two new actin-binding agents on fenestrae dynamics.

Methotrexate and the photodermatitis reactivation reaction: a case report and review of the literature.

Methotrexate is an antimitotic and immunosuppressive agent used for the treatment of cancer, psoriasis, and rheumatologic disorders and for the termination of ectopic pregnancies. Physicians advising patients on the use of methotrexate need to be aware of its possible side effects, including photosensitivity. We present a patient who received methotrexate for the termination of an ectopic pregnancy and experienced a severe reactivation of her sunburn.