Caustic networks with customized intensity statistics.

Controlling random light is a key enabling technology that pioneered statistical imaging methods like speckle microscopy. Such low-intensity illumination is especially useful for bio-medical applications where photobleaching is crucial. Since the Rayleigh intensity statistics of speckles do not always meet the requirements of applications, considerable effort has been dedicated to tailoring their intensity statistics. A special random light distribution that naturally comes with radically different intensity structures to speckles are caustic networks. Their intensity statistics support low intensities while allowing sample illumination with rare rouge-wave-like intensity spikes. However, the control over such light structures is often very limited, resulting in patterns with inadequate ratios of bright and dark areas. Here, we show how to generate light fields with desired intensity statistics based on caustic networks. We develop an algorithm to calculate initial phase fronts for light fields so that they smoothly evolve into caustic networks with the desired intensity statistics during propagation. In an experimental demonstration, we exemplarily realize various networks with a constant, linearly decreasing and mono-exponential probability density function.

High levels of hypusinated eIF5A in leiomyoma and leiomyosarcoma pathologies: a possible novel therapeutic target.

RESEARCH QUESTION: Is the hypusinated form of the eukaryotic translation initiation factor 5A (EIF5A) present in human myometrium, leiomyoma and leiomyosarcoma, and does it regulate cell proliferation and fibrosis? DESIGN: The hypusination status of eIF5A in myometrial and leiomyoma patient-matched tissues was evaluated by immunohistochemistry and Western blotting as well as in leiomyosarcoma tissues by immunohistochemistry. Myometrial, leiomyoma and leiomyosarcoma cell lines were treated with N1-guanyl-1,7-diaminoheptane (GC-7), responsible for the inhibition of the first step of eIF5A hypunization, and the proliferation rate was determined by MTT assay; fibronectin expression was analysed by Western blotting. Finally, expression of fibronectin in leiomyosarcoma tissues was detected by immunohistochemistry. RESULTS: The hypusinated form of eIF5A was present in all tissues examined, with an increasing trend of hypusinated eIF5A levels from normal myometrium to neoplastic benign leiomyoma up to neoplastic malignant leiomyosarcoma. The higher levels in leiomyoma compared with myometrium were confirmed by Western blotting (P = 0.0046). The inhibition of eIF5A hypusination, with GC-7 treatment at 100 nM, reduced the cell proliferation in myometrium (P = 0.0429), leiomyoma (P = 0.0030) and leiomyosarcoma (P = 0.0044) cell lines and reduced the expression of fibronectin in leiomyoma (P = 0.0077) and leiomyosarcoma (P = 0.0280) cells. The immunohistochemical staining of leiomyosarcoma tissue revealed that fibronectin was highly expressed in the malignant aggressive (central) part of the leiomyosarcoma lesion, where hypusinated eIF5A was also highly represented. CONCLUSIONS: These data support the hypothesis that eIF5A may be involved in the pathogenesis of myometrial benign and malignant pathologies.

Dual projectile beams.

Accelerating beams, of which the Airy beam is an important representative, are characterized by intensity maxima that propagate along curved trajectories. In this work we present a simple approach to directly generate accelerating beams with controllable trajectories by means of binary phase structures that consist of only a π phase step modulation in comparison to previous studies where two-dimensional cubic phase modulations for example are required, and which have practical limitations due to their challenging fabrication with phase plates or diffractive optical elements (DOEs), or the spatially extended system needed for their generation at the Fourier plane. In our approach, two intensity maxima are formed that propagate along root parabolic trajectories in contrast to Airy and higher order caustic beams that propagate along a parabolic curve, hence we call these beams Dual Projectile Beams (DPBs). By tailoring a step or slit phase patterns with additional Fresnel lenses, we either generate hollow-core or abruptly focusing beams and control their curvatures. Moreover, using DPBs as a simpler complement to complex structured light fields, we demonstrate their versatility at the example of their interaction with nonlinear matter, namely the formation of a spatial soliton in a photorefractive material. We show that the formed solitary state propagates almost unchanged for a distance of several Rayleigh lengths. This light matter interaction can be regarded as a light beam deceleration. The simplicity of this approach makes these beams suitable for integrated optics and high-power laser applications using DOEs or meta-surfaces.

Uterine leiomyoma as useful model to unveil morphometric and macromolecular collagen state and impairment in fibrotic diseases: An ex-vivo human study.

Collagen is one of the main components of the extracellular matrix (ECM), involved, among all, in the maintenance of the structural support of tissues. In fibrotic diseases, collagen is overexpressed, and its production determines the formation of a significantly stiffer ECM. The cross-linking of high-resolution analytical tools, able to investigate both the tridimensional organization and the secondary structure of collagen in fibrotic diseases, could be useful to identify defined markers correlating the status of this protein with specific pathological conditions. To this purpose, an innovative multidisciplinary approach based on Phase-Contrast MicroComputed Tomography, Transmission Electron Microscopy, and Fourier Transform Infrared Imaging Spectroscopy was exploited on leiomyoma samples and adjacent myometrium to characterize microstructural collagen features. Uterine leiomyoma is a common gynecological disorder affecting women in fertile age. It is characterized by a massive collagen production due to the repairing processes occurring at myometrium level, and, hence, it represents a valuable model to investigate collagen self-organization in a pathological condition. Moreover, to evaluate the sensitivity of this multidisciplinary approach, the effects of eicosapentaenoic (EPA) and docosahexaenoic (DHA) omega-3 fatty acids in collagen reduction were also investigated.

Light transport and localization in disordered aperiodic Mathieu lattices.

Complex optical systems such as deterministic aperiodic Mathieu lattices are known to hinder light diffraction in a manner comparable to randomized optical systems. We systematically incorporate randomness in our complex optical system, measuring its relative contribution of randomness, to understand the relationship between randomness and complexity. We introduce an experimental method for the realization of disordered aperiodic Mathieu lattices with numerically controlled disorder degree. Added disorder always enhances light transport. For lower disorder degrees, we observe diffusive-like transport, and in the range of highest light transport, we detect Anderson localization. With further increase of disorder degree, light transport is slowly decreasing and localization length decreases indicating more pronounced Anderson localization. Numerical investigation at longer propagation distances indicates that the threshold of Anderson localization detection is shifted to lower disorder degrees.

Uterine fibroid vascularization: from morphological evidence to clinical implications.

Uterine fibroids are the most common cause of solid pelvic tumours, occurring in 20-30% of fertile women and presenting clinical complications that seriously affect women's health. They commonly cause severe symptoms, such as heavy, prolonged menstrual bleeding and anaemia. The study of microscopic and macroscopic vascular aspects of uterine fibroids is important for understanding the clinical manifestations of uterine fibroids, for predicting the effectiveness of alternative treatments to surgery, i.e. uterine artery embolization, for improving surgery outcomes and for carrying out a differential diagnosis with other benign conditions, e.g. adenomyosis, or malignancy, e.g. leiomyosarcoma, and to develop new therapeutic approaches. In this review, current knowledge of how the vascular network and angiogenesis are implied in the formation of uterine fibroids and in the pathogenesis of related symptoms is explored, and evidence on the role of ultrasound in evaluating fibroid vascularization is summarized. This review combines anatomical, morphological and biomolecular information related to angiogenic mechanisms with diagnostic and clinical information, highlighting the various interconnections. Uterine and fibroid vascularization need further investigation to gain a deeper understanding of the pathogenetic elements that lead to the formation of uterine fibroids and their clinical manifestations.

Phytoprogestins: Unexplored Food Compounds with Potential Preventive and Therapeutic Effects in Female Diseases.

In recent years, there has been an increasing interest in natural therapies to prevent or treat female diseases. In particular, many studies have focused on searching natural compounds with less side effects than standard hormonal therapies. While phytoestrogen-based therapies have been extensively studied, treatments with phytoprogestins reported in the literature are very rare. In this review, we focused on compounds of natural origin, which have progestin effects and that could be good candidates for preventing and treating female diseases. We identified the following phytoprogestins: kaempferol, apigenin, luteolin, and naringenin. In vitro studies showed promising results such as the antitumoral effects of kaempferol, apigenin and luteolin, and the anti-fibrotic effects of naringenin. Although limited data are available, it seems that phytoprogestins could be a promising tool for preventing and treating hormone-dependent diseases.

Macrophages and Immune Responses in Uterine Fibroids.

Uterine fibroids represent the most common benign tumors of the uterus. They are considered a typical fibrotic disorder. In fact, the extracellular matrix (ECM) proteins-above all, collagen 1A1, fibronectin and versican-are upregulated in this pathology. The uterine fibroids etiology has not yet been clarified, and this represents an important matter about their resolution. A model has been proposed according to which the formation of an altered ECM could be the result of an excessive wound healing, in turn driven by a dysregulated inflammation process. A lot of molecules act in the complex inflammatory response. Macrophages have a great flexibility since they can assume different phenotypes leading to the tissue repair process. The dysregulation of macrophage proliferation, accumulation and infiltration could lead to an uncontrolled tissue repair and to the consequent pathological fibrosis. In addition, molecules such as monocyte chemoattractant protein-1 (MCP-1), granulocyte macrophage-colony-stimulating factor (GM-CSF), transforming growth factor-beta (TGF-ß), activin A and tumor necrosis factor-alfa (TNF-α) were demonstrated to play an important role in the macrophage action within the uncontrolled tissue repair that contributes to the pathological fibrosis that represents a typical feature of the uterine fibroids.

Shaping caustics into propagation-invariant light.

Structured light has revolutionized optical particle manipulation, nano-scaled material processing, and high-resolution imaging. In particular, propagation-invariant light fields such as Bessel, Airy, or Mathieu beams show high robustness and have a self-healing nature. To generalize such beneficial features, these light fields can be understood in terms of caustics. However, only simple caustics have found applications in material processing, optical trapping, or cell microscopy. Thus, these technologies would greatly benefit from methods to engineer arbitrary intensity shapes well beyond the standard families of caustics. We introduce a general approach to arbitrarily shape propagation-invariant beams by smart beam design based on caustics. We develop two complementary methods, and demonstrate various propagation-invariant beams experimentally, ranging from simple geometric shapes to complex image configurations such as words. Our approach generalizes caustic light from the currently known small subset to a complete set of tailored propagation-invariant caustics with intensities concentrated around any desired curve.

Quercetin and indole-3-carbinol inhibit extracellular matrix expression in human primary uterine leiomyoma cells.

RESEARCH QUESTION: What is the effect of quercetin and indole-3-carbinol (I3C) on extracellular matrix expression, cell migration and proliferation in human myometrial and uterine leiomyoma cells. DESIGN: Myometrial and leiomyoma cells were treated with quercetin or I3C at different concentrations (10 µg/ml; 50 µg/ml; 100 µg/ml; and 250 µg/ml) for 48 h to measure mRNA and protein expressions of extracellular matrix (collagen 1A1, fibronectin and versican), as well as cell migration and the proliferation rate. RESULTS: Quercetin decreased mRNA levels of collagen 1A1 in myometrial (P < 0.0001) and leiomyoma cells (P < 0.0001). Quercetin reduced mRNA and protein levels of fibronectin in myometrial cells (P < 0.05) and fibronectin protein in leiomyoma cells (P < 0.05). I3C reduced collagen 1A1 mRNA levels in myometrial (P < 0.05) and leiomyoma cells at higher dose (P < 0.05). The protein levels of fibronectin were also reduced in both myometrial and leiomyoma cells with highest dose of I3C (P < 0.05), although mRNA levels were not affected in leiomyoma cells. Neither quercetin nor I3C treatment altered versican mRNA levels in both cell types. A significant reduction of the migration of both myometrial and leiomyoma cells in response to quercetin was observed (P < 0.05) and I3C (P < 0.05 for myometrial and P < 0.01 for leiomyoma cells) treatment. Both quercetin and I3C significantly reduced myometrial cell proliferation (P < 0.05). CONCLUSIONS: The in-vitro anti-fibrotic, anti-migratory and anti-proliferative effects of quercetin and I3C form the scientific basis for developing new therapeutic, preventive agents, or both, for uterine leiomyomas.

Advanced 3D Imaging of Uterine Leiomyoma's Morphology by Propagation-based Phase-Contrast Microtomography.

Uterine leiomyoma is the most common benign smooth muscle tumor in women pelvis, originating from the myometrium. It is caused by a disorder of fibrosis, with a large production and disruption of extracellular matrix (ECM). Medical treatments are still very limited and no preventative therapies have been developed. We supposed that synchrotron-based phase-contrast microtomography (PhC-microCT) may be an appropriate tool to assess the 3D morphology of uterine leiomyoma, without the use of any contrast agent. We used this technique to perform the imaging and the quantitative morphometric analysis of healthy myometrium and pathologic leiomyomas. The quantitative morphometric analysis of collagen bundles was coupled to the Roschger approach. This method, previously only used to evaluate mineralized bone density distribution, was applied here to study the fibrosis mass density distribution in healthy and pathologic biopsies from two patients. This protocol was shown to be powerful in studying uterine leiomyomas, detecting also small signs of the ECM alteration. This is of paramount importance not only for the follow-up of the present study, i.e. the investigation of different compounds and their possible therapeutic benefits, but also because it offers new methodologic possibilities for future studies of the ECM in soft tissues of different body districts.

Morphing discrete diffraction in nonlinear Mathieu lattices.

Discrete optical gratings are essential components to customize structured light waves, determined by the band structure of the periodic potential. Beyond fabricating static devices, light-driven diffraction management requires nonlinear materials. Up to now, nonlinear self-action has been limited mainly to discrete spatial solitons. Discrete solitons, however, are restricted to the eigenstates of the photonic lattice. Here, we control light formation by nonlinear discrete diffraction, allowing for versatile output diffraction states. We observe morphing of diffraction structures for discrete Mathieu beams propagating nonlinearly in photosensitive media. The self-action of a zero-order Mathieu beam in a nonlinear medium shows characteristics similar to discrete diffraction in one-dimensional waveguide arrays. Mathieu beams of higher orders show discrete diffraction along curved paths, showing the fingerprint of respective two-dimensional photonic lattices.

Omega-3 fatty acids modulate the lipid profile, membrane architecture, and gene expression of leiomyoma cells.

Uterine leiomyomas (fibroids or myomas) are the most common benign tumors of premenopausal women and new medical treatments are needed. This study aimed to determine the effects of omega-3 fatty acids on the lipid profile, membrane architecture and gene expression patterns of extracellular matrix components (collagen1A1, fibronectin, versican, or activin A), mechanical signaling (integrin ß1, FAK, and AKAP13), sterol regulatory molecules (ABCG1, ABCA1, CAV1, and SREBF2), and mitochondrial enzyme (CYP11A1) in myometrial and leiomyoma cells. Myometrial tissues had a higher amount of arachidonic acid than leiomyoma tissues while leiomyoma tissues had a higher level of linoleic acid than myometrial tissues. Treatment of primary myometrial and leiomyoma cells with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) reduced the monounsaturated fatty acid (MUFA) content and increased the polyunsaturated fatty acid (PUFA) content in both cell types. Myometrial and leiomyoma cell membranes were in the liquid-crystalline phase, but EPA- and DHA-treated cells had decreased membrane fluidity. While we found no changes in the mRNA expression of ECM components, EPA and DHA treatment reduced levels of ABCG1, ABCA1, and AKAP13 in both cell types. EPA and DHA also reduced FAK and CYP11A1 expression in myometrial cells. The ability of omega-3 fatty acids to remodel membrane architecture and downregulate the expression of genes involved in mechanical signaling and lipid accumulation in leiomyoma cells offers to further investigate this compound as preventive and/or therapeutic option.