Downregulation of IL-8 and IL-10 by LRRC8A Inhibition through the NOX2-Nrf2-CEBPB Transcriptional Axis in THP-1-Derived M Macrophages.

M-polarized, tumor-associated macrophages (TAMs) produce pro-tumorigenic and angiogenic mediators, such as interleukin-8 (IL-8) and IL-10. Leucine-rich repeat-containing protein 8 members (LRRC8s) form volume-regulated anion channels and play an important role in macrophage functions by regulating cytokine and chemokine production. We herein examined the role of LRRC8A in IL-8 and IL-10 expression in THP-1-differentiated M-like macrophages (M-MACs), which are a useful tool for investigating TAMs.

Transcriptional Up-Regulation of FBXW7 by K1.1 K Channel Inhibition through the Nrf2 Signaling Pathway in Human Prostate Cancer LNCaP Cell Spheroid Model.

The tumor suppressor gene F-box and WD repeat domain-containing (FBXW) 7 reduces cancer stemness properties by promoting the protein degradation of pluripotent stem cell markers. We recently demonstrated the transcriptional repression of FBXW7 by the three-dimensional (3D) spheroid formation of several cancer cells. In the present study, we found that the transcriptional activity of FBXW7 was promoted by the inhibition of the Ca-activated K channel, K1.

The Effects of a Red-Light Controllable Nitric Oxide Donor, NORD-1, on Erectile Dysfunction in Rats with Streptozotocin Induced Diabetes Mellitus.

Purpose: Patients with diabetes mellitus (DM) often exhibit refractory erectile dysfunction (ED). Red-light-controllable nitric oxide donor (NORD-1) and red-light irradiation have successfully enhanced erectile function in intact rats. In this study, we investigated whether the combination of NORD-1 and red-light irradiation effectively treated ED in streptozotocin (STZ)-treated rats with DM.

Field-Free Spin-Orbit Torque Magnetization Switching in a Perpendicularly Magnetized Semiconductor (Ga,Mn)As Single Layer.

Current-induced spin-orbit torque (SOT) in a perpendicularly magnetized single layer has a strong potential to switch the magnetization using an extremely low current density, which is generally 2-3 orders of magnitude smaller than that required for conventional metal bilayer systems. However, an in-plane external magnetic field has to be applied to break the symmetry and achieve deterministic switching. To further enhance the high-density integration and accelerate the practical application of highly efficient SOT magnetic random-access memory (SOT-MRAM) devices, field-free SOT magnetization switching in a ferromagnetic single layer is strongly needed.

Colossal Magnetoresistive Switching Induced by d Ferromagnetism of MgO in a Semiconductor Nanochannel Device with Ferromagnetic Fe/MgO Electrodes.

Exploring potential spintronic functionalities in resistive switching (RS) devices is of great interest for creating new applications, such as multifunctional resistive random-access memory and novel neuromorphic computing devices. In particular, the importance of the spin-triplet state of cation vacancies in oxide materials, which is induced by localized and strong O-2p on-site Coulomb interactions, in RS devices has been overlooked. d ferromagnetism sometimes appears due to the spin-triplet state and ferromagnetic Zener's double exchange interactions between cation vacancies, which are occasionally strong enough to make nonmagnetic oxides ferromagnetic.

Magnetic field observation in a magnetic tunnel junction by scanning transmission electron microscopy.

A magnetic tunnel junction (MTJ) consists of two ferromagnetic layers separated by a thin insulating layer. MTJs show tunnel magnetoresistance effect, where the resistance in the direction perpendicular to the insulator layer drastically changes depending on the magnetization directions (parallel or antiparallel) in the ferromagnetic layers. However, direct observation of local magnetizations inside MTJs has been challenging.

Down-Regulation of CYP3A4 by the K1.1 Inhibition Is Responsible for Overcoming Resistance to Doxorubicin in Cancer Spheroid Models.

The large-conductance Ca-activated K channel, K1.1, plays a pivotal role in cancer progression, metastasis, and the acquisition of chemoresistance. Previous studies indicated that the pharmacological inhibition of K1.

[Overcoming chemoresistance by Ca-activated K channel inhibition in cancer spheroid models].

Ca-activated K channels play a critical role in the proliferation, apoptosis, migration, adhesion, and metastasis of various types of cancer cells by controlling Ca signaling and cell volumes. Their amplification correlated with a high tumor stage and poor prognosis and has the potential as tumor grade-associated markers. The amplification of the large-conductance Ca-activated K channel, K1.

Endoscopic Manifestations and Clinical Characteristics of Localized Gastric Light-Chain Amyloidosis.

To determine the endoscopic and clinical features of localized gastric amyloid light-chain (AL) amyloidosis, we retrospectively examined the characteristics of nine patients (eight men and one woman) encountered by the hospitals in our network. Lesions were predominantly flat and depressed with surface vascular dilatation (n=5); others were characterized by subepithelial lesions (n=2), mucosal color change (n=1), and a mass-like morphology with swollen mucosal folds (n=1). Colonoscopy (n=7), video capsule enteroscopy (n=2), serum (n=5) and urine immunoelectrophoresis (n=4), and bone marrow examination (n=3) were performed to exclude involvement of organs other than the stomach.

K3.1 regulates cell cycle progression by modulating Ca signaling in murine preosteoblasts.

Osteoblasts synthesize and deposit essential components of the extracellular bone matrix and collagen scaffolds, leading to mineralized bone formation. Therefore, the proliferation of preosteoblasts (precursors of mature osteoblasts) helps in regulating skeletal homeostasis. This study demonstrated that the functional expression of K3.

Electric Field Control of Spin-Orbit Torque Magnetization Switching in a Spin-Orbit Ferromagnet Single Layer.

To achieve a desirable magnitude of spin-orbit torque (SOT) for magnetization switching and realize multifunctional spin logic and memory devices utilizing SOT, controlling the SOT manipulation is vitally important. In conventional SOT bilayer systems, researchers have tried to control the magnetization switching behavior via interfacial oxidization, modulation of spin-orbit effective field, and effective spin Hall angle; however, the switching efficiency is limited by the interface quality. A current-induced effective magnetic field in a single layer of a ferromagnet with strong spin-orbit interactions, the so-called spin-orbit ferromagnet, can be utilized to induce SOT.

Giant Spin-Valve Effect in Planar Spin Devices Using an Artificially Implemented Nanolength Mott-Insulator Region.

Developing technology to realize oxide-based nanoscale planar integrated circuits is in high demand for next-generation multifunctional electronics. Oxide circuits can have a variety of unique functions, including ferromagnetism, ferroelectricity, multiferroicity, superconductivity, and mechanical flexibility. In particular, for spin-transistor applications, the wide tunability of the physical properties due to the presence of multiple oxide phases is valuable for precise conductivity matching between the channel and ferromagnetic electrodes.

Autologous Synovial Mesenchymal Stem Cell Transplantation Suppresses Inflammation Caused by Synovial Harvesting and Promotes Healing in a Micro Minipig Repaired Meniscus Model.

Purpose: Allogeneic synovial mesenchymal stem cells (MSCs) effectively promote meniscus healing in micro minipigs. We investigated the effect of autologous synovial MSC transplantation on meniscus healing in a micro minipig model of meniscus repair showing synovitis after synovial harvesting.

Materials And Methods: Synovium was harvested from the left knee of the micro minipigs after arthrotomy and used to prepare synovial MSCs.

Giant spin-to-charge conversion at an all-epitaxial single-crystal-oxide Rashba interface with a strongly correlated metal interlayer.

The two-dimensional electron gas (2DEG) formed at interfaces between SrTiO (STO) and other oxide insulating layers is promising for use in efficient spin-charge conversion due to the large Rashba spin-orbit interaction (RSOI). However, these insulating layers on STO prevent the propagation of a spin current injected from an adjacent ferromagnetic layer. Moreover, the mechanism of the spin-current flow in these insulating layers is still unexplored.

Downregulation of IL-8 and IL-10 by the Activation of Ca-Activated K Channel K3.1 in THP-1-Derived M Macrophages.

THP-1-differentiated macrophages are useful for investigating the physiological significance of tumor-associated macrophages (TAMs). In the tumor microenvironment (TME), TAMs with the M-like phenotype play a critical role in promoting cancer progression and metastasis by inhibiting the immune surveillance system. We examined the involvement of Ca-activated K channel K3.

Identification of responsible amino acid residues in staphylococcal superantigen-like 12 for the activation of mast cells.

Staphylococcal superantigen-like 12 (SSL12) is reported to evoke the degranulation in murine mast cells. The allelic variant of SSL12 in the genome of reference strain NCTC8325 induced the degranulation of murine mast cells, that of MRSA252 strain did not, nevertheless relatively high sequence similarity (82%). To identify responsible amino acid residues of SSL12 for mast cell activation, we created a series of domain swap mutants and amino acid substitution mutants between the active and inactive variants.

K1.1 K Channel Inhibition Overcomes Resistance to Antiandrogens and Doxorubicin in a Human Prostate Cancer LNCaP Spheroid Model.

Several types of K channels play crucial roles in tumorigenicity, stemness, invasiveness, and drug resistance in cancer. Spheroid formation of human prostate cancer (PC) LNCaP cells with ultra-low attachment surface cultureware induced the up-regulation of cancer stem cell markers, such as NANOG, and decreased the protein degradation of the Ca-activated K channel K1.1 by down-regulating the E3 ubiquitin ligase, FBXW7, compared with LNCaP monolayers.

K3.1 inhibition-induced activation of the JNK/c-Jun signaling pathway enhances IL-10 expression in peripherally-induced regulatory T cells.

The K3.1 inhibition up-regulates IL-10 expression in regulatory T (T) cells in the recovery phase of inflammatory bowel disease (IBD) model mice; however, the underlying signaling pathway remains unclear. We investigated the involvement of AP-1 (Fos/Jun) and NF-κB in the expression of IL-10 and its transcription factors (TFs) in in vitro-induced mouse splenic T cells.

Role of K and Ca-Permeable Channels in Osteoblast Functions.

Bone-forming cells or osteoblasts play an important role in bone modeling and remodeling processes. Osteoblast differentiation or osteoblastogenesis is orchestrated by multiple intracellular signaling pathways (e.g.

Ca -activated K channel K 1.1 as a therapeutic target to overcome chemoresistance in three-dimensional sarcoma spheroid models.

The large-conductance Ca -activated K channel K 1.1 plays a pivotal role in tumor development and progression in several solid cancers. The three-dimensional (3D) in vitro cell culture system is a powerful tool for cancer spheroid formation, and mimics in vivo solid tumor resistance to chemotherapy in the tumor microenvironment (TME).

[Use of pegylated granulocyte colony-stimulating factor in dose-adjusted EPOCH-R therapy].

Dose-adjusted (DA)-EPOCH-R causes profound neutropenia requiring relatively long hospital stays with multiple doses of granulocyte colony-stimulating factor (G-CSF). A single-dose pegylated G-CSF (PEG-G-CSF) has been used for the treatment of chemotherapy-induced neutropenia. We retrospectively examined 15 patients (median age 61, range 33-75 years) treated with DA-EPOCH-R.