Microglial xCT Is a Novel Therapeutic Target for Traumatic Brain Injury in Model Mice.

Background: Brain injury accompanied by hemorrhage, such as cerebral contusion or intracerebral hemorrhage, leads to the accumulation of activated microglia around the lesion. In addition, microglia at the site of injury can act either damagingly or protectively, depending on the time; for instance, it is damaging in the acute phase and protective in the chronic phase. Moreover, during brain injury, glutamate-induced excitotoxicity leads to secondary damage to neurons.

Ectopic ULBP2 Is Associated with Decreased NKG2D Expression in CD8 T Cells Under T Cell-Modulatory Conditions in a Murine Tumor Model.

UL16-binding protein 2 (ULBP2), a ligand for the activating receptor NKG2D, plays a dual role in tumor immunity, promoting immune activation or suppression, depending on the context. To investigate its impact on CD4CD25 T cell-targeted immunotherapies, we used a syngeneic CT26 colon cancer model engineered to express ULBP2 and compared tumor growth and tumor-infiltrating lymphocyte (TIL) profiles in control and ULBP2-expressing tumors treated with anti-CD4, anti-CD25, or anti-CTLA-4 antibodies. Tumor growth was uniformly assessed on day 21 post-transplantation, and TIL analysis was performed in groups with evaluable residual tumors.

N-Methyladenosine Reader Protein YTHDC1 Supports Proper Mitotic Progression Partly through Regulation of TPX2-Aurora A Signaling.

Chemical modification of mRNA regulates its stability and translation efficiency. The most prevalent modification is the N-methyladenosine (mA) modification. YT521-B homology domain-containing proteins (YTHDCs) are "reader" proteins of mA modification and contribute to various cell functions by regulating their target mA-containing mRNAs.

Two Brothers With ADSS1 Myopathy: A Report of Clinical, Radiological, and Autopsy Findings.

ADSS1 myopathy, previously known as adenylosuccinate synthetase-like 1 (ADSSL1) myopathy, is an autosomal recessive muscle disease caused by variants in ADSS1 (adenylosuccinate synthase 1). ADSS1 myopathy is complicated by respiratory muscle weakness or cardiomyopathy as well as limb muscle weakness. We analyzed two siblings with ADSS1 myopathy, both harboring compound heterozygous pathogenic variants (c.

ULBP2 Promotes Tumor Progression by Suppressing NKG2D-Mediated Anti-Tumor Immunity.

UL-16 binding protein 2 (ULBP2), a human NKG2D ligand, has been identified as a poor prognostic factor in several cancers based on recent comprehensive analyses of immune-related genes using the Cancer Genome Atlas datasets. Despite its clinical significance, the functional role of ULBP2 in vivo remains largely unknown. In this study, we investigated the role of ULBP2 in modulating anti-tumor immunity using murine melanoma cell lines engineered to stably express surface-expressed or soluble ULBP2.

Long-Term Management of a Patient With Obstructive Sleep Apnea Using Multimodal Combination Treatment.

In this case, we combined oral appliance, continuous positive airway pressure, and sleep surgery for the management of obstructive sleep apnea. It will require a combination of therapies according to the patient's chief complaint and symptoms and not just one therapy for the long-term management of obstructive sleep apnea.

DeSUMOylating isopeptidase 1 participates in the faithful chromosome segregation and vincristine sensitivity.

SUMOylation, the modification of proteins with a small ubiquitin-like modifier (SUMO), is known to regulate various cellular events, including cell division. This process is dynamic, with its status depending on the balance between SUMOylation and deSUMOylation. While the regulation of cell division by sentrin-specific protease (SENP) family proteins through deSUMOylation has been investigated, the role of another deSUMOylase, deSUMOylating isopeptidase 1 (DESI1), remains unknown.

Phosphorylation of Ephexin4 at Ser-41 contributes to chromosome alignment via RhoG activation in cell division.

Ephexin proteins are guanine nucleotide exchange factors for the Rho GTPases. We reported that Ephexin4 regulates M-phase progression downstream of phosphorylated EphA2, a receptor-type tyrosine kinase, through RhoG activation; however, the regulation of Ephexin4 during M phase remains unknown. In this study, a novel Ephexin4 phosphorylation site was identified at Ser41, exclusively in M phase.

TNK2 Inhibitor (R)-9bMS Causes Polyploidization Through Mitotic Failure by Targeting Aurora B.

TNK2 is a ubiquitously expressed nonreceptor-type tyrosine kinase. TNK2 participates in tumorigenesis, and TNK2 activation has been found in various cancers; therefore, TNK2 is a promising target for cancer chemotherapy. While the TNK2 inhibitor XMD16-5 is highly selective, it inhibits cytokinesis at higher concentrations by targeting Aurora B kinase, a key enzyme for cell division.

LAT1 supports mitotic progression through Golgi unlinking in an amino acid transport activity-independent manner.

Amino acid transporters play a vital role in cellular homeostasis by maintaining protein synthesis. L-type amino acid transporter 1 (LAT1/SLC7A5/CD98lc) is a major transporter of large neutral amino acids in cancer cells because of its predominant expression. Although amino acid restriction with various amino acid analog treatments is known to induce mitotic defects, the involvement of amino acid transporters in cell division remains unclear.

Exosomal miR-493 suppresses MAD2L1 and induces chemoresistance to intraperitoneal paclitaxel therapy in gastric cancer patients with peritoneal metastasis.

Intraperitoneal (IP) chemotherapy with paclitaxel (PTX) for gastric cancer (GC) with peritoneal metastasis (PM) is considered a promising treatment approach, however, there are no useful biomarkers to predict the efficacy of IP therapy. We examined the association between intra-peritoneal exosomes, particularly exosomal micro-RNAs (exo-miRNAs), and IP-chemo sensitivity. MKN45 cells that were cultured with intra-peritoneal exosomes from patients who did not respond to IP therapy with PTX (IP group) exhibited resistance to PTX compared with exosomes from responding patients (IP group) (p = 0.

Simvastatin activates the spindle assembly checkpoint and causes abnormal cell division by modifying small GTPases.

Simvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, which is a rate-limiting enzyme of the cholesterol synthesis pathway. It has been used clinically as a lipid-lowering agent to reduce low-density lipoprotein (LDL) cholesterol levels. In addition, antitumor activity has been demonstrated.

Linderapyrone analogue LPD-01 as a cancer treatment agent by targeting importin7.

The Wnt/β-catenin signaling pathway plays important roles in several cancer cells, including cell proliferation and development. We previously succeeded in synthesizing a small molecule compound inhibiting the Wnt/β-catenin signaling pathway, named LPD-01 (1), and 1 inhibited the growth of human colorectal cancer (HT-29) cells. In this study, we revealed that 1 inhibits the growth of HT-29 cells stronger than that of another human colorectal cancer (SW480) cells.

Highly genomic instability of super-polyploid strains of Saccharomyces cerevisiae.

Polyploid (2n, 3n, and 4n) genomes are known to be unstable in Saccharomyces cerevisiae. Here, we attempted construction of super-polypoid strains (defined as having higher ploidy than tetraploidy) up to 32n by using the matα2-PBT method that we newly developed and investigated their genomic stability. It is known that cell size increases as ploidy increases up to tetraploid.

Eph signal inhibition potentiates the growth-inhibitory effects of PLK1 inhibition toward cancer cells.

Anti-mitotic drugs are clinically used as anti-cancer treatments. Polo-like kinase 1 (PLK1) is a promising target against cancer cell division due to its importance in the whole process of mitosis, and thus PLK1-targeting agents have been developed in the last few decades. Clinical trial studies show that several PLK1 inhibitors are generally well-tolerated.

Phosphotyrosine proteomics in cells synchronized at monopolar cytokinesis reveals EphA2 as functioning in cytokinesis.

Cytokinesis is the final step of the cell division in which cellular components are separated into two daughter cells. This process is regulated through the phosphorylation of different classes of proteins by serine/threonine (Ser/Thr) kinases such as Aurora B and Polo-like kinase 1 (PLK1). Conversely, the role of phosphorylation at tyrosine residues during cytokinesis has not been studied in detail yet.

The C-terminal tail of Rad17, iVERGE, binds the 9‒1‒1 complex independently of AAA+ ATPase domains to provide another clamp-loader interface.

The ATR pathway plays a crucial role in maintaining genome integrity as the major DNA damage checkpoint. It also attracts attention as a therapeutic target in cancer treatment. The Rad17-RFC2-5 complex loads the Rad9-Hus1-Rad1 (9-1-1) DNA clamp complex onto damaged chromatin to activate the ATR pathway.

Distinct effects of heat shock temperatures on mitotic progression by influencing the spindle assembly checkpoint.

Heat shock is a physiological and environmental stress that leads to the denaturation and inactivation of cellular proteins and is used in hyperthermia cancer therapy. Previously, we revealed that mild heat shock (42 °C) delays the mitotic progression by activating the spindle assembly checkpoint (SAC). However, it is unclear whether SAC activation is maintained at higher temperatures than 42 °C.

Epstein-Barr virus reactivation in peripheral B lymphocytes induces IgM-type thyrotropin receptor autoantibody production in patients with Graves' disease.

Epstein-Barr virus (EBV) is a human herpes virus that latently infects B lymphocytes. When EBV is reactivated, host B cells differentiate into plasma cells and produce IgM-dominant antibodies as well as many progeny virions. The aims of the present study were to confirm the IgM dominance of thyrotropin-receptor antibodies (TRAbs) produced by EBV reactivation and investigate the roles of TRAb-IgM in Graves' disease.

SH2D4A promotes centrosome maturation to support spindle microtubule formation and mitotic progression.

Mitotic progression requires the precise formation of spindle microtubules based on mature centrosomes. During the G2/M transition, centrosome maturation progresses, and associated microtubules bundle to form mitotic spindle fibers and capture the chromosomes for alignment at the cell equator. Mitotic kinases-induced phosphorylation signaling is necessary for these processes.

Azaphilones produced by Penicillium maximae with their cell death-inducing activity on Adriamycin-treated cancer cell.

Background: Heat shock proteins (Hsps) are overexpressed in several tumors and contribute to cell proliferation, metastasis, and anticancer drug resistance. Therefore, Hsp inhibitors have enhanced cytotoxicity as chemotherapeutic agents and may be effective with a reduced dosage for tumor therapy to avoid side effects.

Results: Four new azaphilones, maximazaphilones I-IV (1-4), and three known compounds (5-7) have been isolated from the airborne-derived fungus Penicillium maximae.