Scanning Electron Microscopy of the Microvascular System in the Inner Ear

In the present work, vessels casts in the inner ear of the rat and guinea pig, prepared by casting method using Mercox resin, were subjected to scanning electron microscopic examination and following results were obtained: 1) In adult guinea pig, numerous capillary nets were found in the following parts: stria vascularis, spiral ligament, spiral prominence, Corti\u27s organ, spiral ganglion, plexus cochlearis, semicircular ampulla, saccule, utricle, and endolymphatic sac. These were consistent with functionally and morophologically important areas in the inner ear. 2) In the central side of the area with capillary nets, arterioles were found to run throughout, like a complex coil, and peripheral capillary diameter was found to be unchanged in an experiment in which the injection pressure was altered, thus autoregulation of blood flow into these important areas is assumed. 3) Vessels in the planum semilunatum were found to form a specific loop-shaped route, where secretion and reabsorption of endolymph is thought to occur. 4) After kanamycin injection into the tympanic cavity, stenosis was observed in capillary nets in the cochlear lateral wall. 5) In guinea pigs on the 30th day of fetal life, the main stem of the inner ear vessel had already formed; however, the peripheral capillary nets were as yet immature in form and vessel density was low

Influence of Input Energy Density on Morphology of Unique Layered Microstructure of γ-TiAl Alloys Fabricated by Electron Beam Powder Bed Fusion

Microstructure and tensile properties of Ti–48Al–2Cr–2Nb (at%) rods fabricated by electron beam powder bed fusion (EB-PBF) process were investigated by changing input energy density (ED) which is one of the important factors affecting formation of the melt pool. We found that unique layered microstructure consisting of an equiaxed γ grain layer (γ band) and a duplex region can be formed by EB-PBF with ED in the range of 13 to 31 J/mm3. It is interesting to note that the width of the γ band and the volume fraction of the γ phase in the duplex region decrease with increasing ED. On the other hand, the α2/γ lamellar grain in the duplex region increases with increasing ED. These morphological changes in the layered microstructure are attributed to variation of temperature distribution from melt pool caused by increasing ED. Moreover, we also found for the first time the strength of the alloys can be improved by decreasing width of the γ band and increasing of the α2/γ lamellar grain in the duplex region. Whereas, the width of the γ band and the fraction of the equiaxed γ grain in the duplex region should be increased to enhance ductility of the alloys.Cho Ken, Morita Naohide, Matsuoka Hiromasa, et al. Influence of Input Energy Density on Morphology of Unique Layered Microstructure of γ-TiAl Alloys Fabricated by Electron Beam Powder Cho Ken, Morita Naohide, Matsuoka Hiromasa, et al. Influence of Input Energy Density on Morphology of Unique Layered Microstructure of γ-TiAl Alloys Fabricated by Electron Beam Powder Bed Fusion. MATERIALS TRANSACTIONS 64, 44 (2023); https://doi.org/10.2320/matertrans.MT-MLA2022015

Inhibition of ADAMTS4 (aggrecanase-1) by tissue inhibitors of metalloproteinases (TIMP-1, 2, 3 and 4)

AbstractADAMTS4 (aggrecanase-1) is considered to play a key role in the degradation of aggrecan in arthritides. The inhibitory activity of tissue inhibitors of metalloproteinases (TIMPs) to ADAMTS4 was examined in an assay using aggrecan substrate. Among the four TIMPs, TIMP-3 inhibited the activity most efficiently with an IC50 value of 7.9 nM, which was at least 44-fold lower than that of TIMP-1 (350 nM) and TIMP-2 (420 nM) and >250-fold less than that of TIMP-4 (2 μM for 35% inhibition). These results suggest that TIMP-3 is a potent inhibitor against the aggrecanase activity of ADAMTS4 in vivo

Reverse Engineering a Signaling Network Using Alternative Inputs

One of the goals of systems biology is to reverse engineer in a comprehensive fashion the arrow diagrams of signal transduction systems. An important tool for ordering pathway components is genetic epistasis analysis, and here we present a strategy termed Alternative Inputs (AIs) to perform systematic epistasis analysis. An alternative input is defined as any genetic manipulation that can activate the signaling pathway instead of the natural input. We introduced the concept of an “AIs-Deletions matrix” that summarizes the outputs of all combinations of alternative inputs and deletions. We developed the theory and algorithms to construct a pairwise relationship graph from the AIs-Deletions matrix capturing both functional ordering (upstream, downstream) and logical relationships (AND, OR), and then interpreting these relationships into a standard arrow diagram. As a proof-of-principle, we applied this methodology to a subset of genes involved in yeast mating signaling. This experimental pilot study highlights the robustness of the approach and important technical challenges. In summary, this research formalizes and extends classical epistasis analysis from linear pathways to more complex networks, facilitating computational analysis and reconstruction of signaling arrow diagrams

Broad targeting of resistance to apoptosis in cancer

Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer

A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes

Cell fusions in mammals

Cell fusions are important to fertilization, placentation, development of skeletal muscle and bone, calcium homeostasis and the immune defense system. Additionally, cell fusions participate in tissue repair and may be important to cancer development and progression. A large number of factors appear to regulate cell fusions, including receptors and ligands, membrane domain organizing proteins, proteases, signaling molecules and fusogenic proteins forming alpha-helical bundles that bring membranes close together. The syncytin family of proteins represent true fusogens and the founding member, syncytin-1, has been documented to be involved in fusions between placental trophoblasts, between cancer cells and between cancer cells and host cells. We review the literature with emphasis on the syncytin family and propose that syncytins may represent universal fusogens in primates and rodents, which work together with a number of other proteins to regulate the cell fusion machinery

Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies

Objectives: The purpose of this document is to make the output of the International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT) Standardization and Validation available to medical and scientific communities, through a peer-reviewed publication, in the interest of improving the diagnosis and treatment of patients with atherosclerosis, including coronary artery disease. Background: Intravascular optical coherence tomography (IVOCT) is a catheter-based modality that acquires images at a resolution of ∼10 μm, enabling visualization of blood vessel wall microstructure in vivo at an unprecedented level of detail. IVOCT devices are now commercially available worldwide, there is an active user base, and the interest in using this technology is growing. Incorporation of IVOCT in research and daily clinical practice can be facilitated by the development of uniform terminology and consensus-based standards on use of the technology, interpretation of the images, and reporting of IVOCT results. Methods: The IWG-IVOCT, comprising more than 260 academic and industry members from Asia, Europe, and the United States, formed in 2008 and convened on the topic of IVOCT standardization through a series of 9 national and international meetings. Results: Knowledge and recommendations from this group on key areas within the IVOCT field were assembled to generate this consensus document, authored by the Writing Committee, composed of academicians who have participated in meetings and/or writing of the text. Conclusions: This document may be broadly used as a standard reference regarding the current state of the IVOCT imaging modality, intended for researchers and clinicians who use IVOCT and analyze IVOCT data