Growth Hormone Protects Against Ovariectomy-Induced Bone Loss in States of Low Circulating Insulin-like Growth Factor (IGF-1)*

Early after estrogen loss in postmenopausal women and ovariectomy (OVX) of animals, accelerated endosteal bone resorption leads to marrow expansion of long bone shafts that reduce mechanical integrity. Both growth hormone (GH) and insulin-like growth factor (IGF-1) are potent regulators of bone remodeling processes. To investigate the role of the GH/IGF-1 axis with estrogen deficiency, we used the liver IGF-1-deficient (LID) mouse. Contrary to deficits in controls, OVX of LID mice resulted in maintenance of cortical bone mechanical integrity primarily owing to an enhanced periosteal expansion affect on cross-sectional structure (total area and cortical width). The serum balance in LID that favors GH over IGF-1 diminished the effects of ablated ovarian function on numbers of osteoclast precursors in the marrow and viability of osteocytes within the cortical matrix and led to less endosteal resorption in addition to greater periosteal bone formation. Interactions between estrogen and the GH/IGF-1 system as related to bone remodeling provide a pathway to minimize degeneration of bone tissue structure and osteoporotic fracture. © 2010 American Society for Bone and Mineral Researc

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Microseismic Full Waveform Modeling in Anisotropic Media with Moment Tensor Implementation

Seismic anisotropy which is common in shale and fractured rocks will cause travel-time and amplitude discrepancy in different propagation directions. For microseismic monitoring which is often implemented in shale or fractured rocks, seismic anisotropy needs to be carefully accounted for in source location and mechanism determination. We have developed an efficient finite-difference full waveform modeling tool with an arbitrary moment tensor source. The modeling tool is suitable for simulating wave propagation in anisotropic media for microseismic monitoring. As both dislocation and non-double-couple source are often observed in microseismic monitoring, an arbitrary moment tensor source is implemented in our forward modeling tool. The increments of shear stress are equally distributed on the staggered grid to implement an accurate and symmetric moment tensor source. Our modeling tool provides an efficient way to obtain the Green’s function in anisotropic media, which is the key of anisotropic moment tensor inversion and source mechanism characterization in microseismic monitoring. In our research, wavefields in anisotropic media have been carefully simulated and analyzed in both surface array and downhole array. The variation characteristics of travel-time and amplitude of direct P- and S-wave in vertical transverse isotropic media and horizontal transverse isotropic media are distinct, thus providing a feasible way to distinguish and identify the anisotropic type of the subsurface. Analyzing the travel-times and amplitudes of the microseismic data is a feasible way to estimate the orientation and density of the induced cracks in hydraulic fracturing. Our anisotropic modeling tool can be used to generate and analyze microseismic full wavefield with full moment tensor source in anisotropic media, which can help promote the anisotropic interpretation and inversion of field data

Extracellular Vesicles from Ocular Melanoma Have Pro-Fibrotic and Pro-Angiogenic Properties on the Tumor Microenvironment

Uveal melanoma (UM) is the most common primary intraocular tumor and often spreads to the liver. Intercellular communication though extracellular vesicles (EVs) plays an important role in several oncogenic processes, including metastasis, therapeutic resistance, and immune escape. This study examines how EVs released by UM cells modify stellate and endothelial cells in the tumor microenvironment. The surface markers, and the concentration and size of EVs derived from UM cells or choroidal melanocytes were characterized by high-resolution flow cytometry, electron microscopy, and Western blotting. The selective biodistribution of EVs was studied in mice by fluorescence imaging. The activation/contractility of stellate cells and the tubular organization of endothelial cells after exposure to melanomic EVs were determined by traction force microscopy, collagen gel contraction, or endothelial tube formation assays. We showed that large EVs from UM cells and healthy melanocytes are heterogenous in size, as well as their expression of phosphatidylserine, tetraspanins, and Tsg101. Melanomic EVs mainly accumulated in the liver and lungs of mice. Hepatic stellate cells with internalized melanomic EVs had increased contractility, whereas EV-treated endothelial cells developed more capillary-like networks. Our study demonstrates that the transfer of EVs from UM cells leads to a pro-fibrotic and pro-angiogenic phenotype in hepatic stellate and endothelial cells