Targeting Non-Apoptotic Pathways with the Cell Permeable TAT-Conjugated NOTCH1 RAM Fragment for Leukemia and Lymphoma Cells.

Targeting nonapoptotic cell death offers a promising strategy for overcoming apoptosis resistance in cancer. In this study, we developed Tat-Ram13, a 25-mer peptide that fuses the NOTCH1 intracellular domain fragment RAM13 with a cell-penetrating HIV-1 TAT, for the treatment of T-cell acute lymphoblastic leukemia with aberrant NOTCH1 mutation. Tat-Ram13 significantly downregulated NOTCH1-target genes in T-ALL cell lines.

Functional and structural analyses of IMP-27 metallo-β-lactamase: evolution of IMP-type enzymes to overcome Zn(II) deprivation.

IMP-type metallo-β-lactamases are di-Zn(II) enzymes that can inactivate a wide range of bicyclic β-lactam agents used in clinical practice. IMP-27 shares 82% amino acid sequence identity with IMP-1, the first IMP-type enzyme identified. Herein, we conducted structural determination, kinetic, and chelating agent resistance analyses of IMP-27.

Lipopolysaccharide Derived from Directly Promotes the Migration of Human Keratinocytes.

Background/aim: Because the skin is exposed to the external environment, it is important that wound healing processes proceed and terminate rapidly to minimize the risk of infection. A previous case report described the promotion of wound healing by transdermal administration of lipopolysaccharide derived from Pantoea agglomerans (LPSp). However, whether the wound healing-promoting effect of LPSp was due to direct activity on skin cells or indirect effects involving macrophages remained unclear.

Restoration of Spatial Learning Through Oral Administration of Lipopolysaccharides in Diabetes-related Cognitive Dysfunction.

Background/aim: In a previous report, our group showed that oral administration of lipopolysaccharides (LPS) from Pantoea agglomerans can prevent the progression of streptozotocin (STZ)-induced diabetes-related cognitive dysfunction (DRCD) in mice without causing significant side-effects. However, the treatment effects of oral administration of LPS to DRCD remain unknown.

Materials And Methods: We modified our previous animal experimental model to investigate whether oral administration of LPS can recover cognitive function after DRCD onset.

Effects of Binding between Ca in Hard Water and Phosphorus in Amylopectin on the Qualities of Boiled Rice and Rice Noodle Prepared by Soaking and Boiling in Hard Water.

Recently, global warming has led to an increase in chalky rice grains. This has consequently resulted in the deterioration in quality of rice products. Although we previously reported that hard water, rich in Ca, is useful for the quality improvement of high-temperature-damaged rice grains, the mechanism was not elucidated sufficiently.

Characteristics of chronic lymphocytic leukemia in Japan: Comprehensive analysis of the CLLRSG-01 study.

Chronic lymphocytic leukemia (CLL) is rare in Japan. We conducted the nationwide, prospective observational study CLLRSG-01 to clarify the current state of CLL in Japan and to make accurate international comparisons by preparing naturally air-dried smears like those used in other countries. Of the 201 untreated patients enrolled and evaluated, 119 were diagnosed with CLL and 82 with non-CLL mature B-cell neoplasms, based on the WHO classification.

Mass spectrometry-based proteomic analysis of proteins adsorbed by hexadecyl-immobilized cellulose bead column for the treatment of dialysis-related amyloidosis.

Background: Dialysis-related amyloidosis (DRA) is a severe complication in end-stage kidney disease (ESKD) patients undergoing long-term dialysis treatment, characterized by the deposition of β-microglobulin-related amyloids (Aβ2M amyloid). To inhibit DRA progression, hexadecyl-immobilized cellulose bead (HICB) columns are employed to adsorb circulating β-microglobulin (β2M). However, it is possible that the HICB also adsorbs other molecules involved in amyloidogenesis.

Relationship between Ca and cAMP as second messengers in ACTH-induced cortisol production in bovine adrenal fasciculata cells.

In adrenal fasciculata cells stimulated by ACTH, Ca and cAMP play indispensable roles as second messengers in cortisol production. However, whether their second messengers cooperatively or independently participate in steroid production remains unclear. We focused on the roles of Ca and cAMP in cortisol production in bovine adrenal fasciculata cells stimulated by ACTH for a relatively short period (1 h).

Utility of In Vitro Cellular Models of Low-Dose Lipopolysaccharide in Elucidating the Mechanisms of Anti-Inflammatory and Wound-Healing-Promoting Effects of Lipopolysaccharide Administration In Vivo.

Lipopolysaccharide (LPS) is a bacterial component that activates intracellular signaling pathways upon binding to the Toll-like receptor (TLR)-4/MD-2 complex. It is well known that LPS injected into animals and high-dose (100 ng/mL to 1 μg/mL) LPS treatment to innate immune cells induce an inflammatory response. In contrast, LPS is naturally present in the gastrointestinal tract, respiratory tract, and skin of humans and animals, and it has been shown that TLR-4-deficient animals cannot maintain their immune balance and gut homeostasis.

DNA-dependent protein kinase catalytic subunit binds to the transactivation domain 1 of NF-κB p65.

Nuclear factor-kappa B (NF-κB) is a transcriptional factor that binds to the ∼10-base-pair κB motif on target genes and acts as an inflammatory regulator. Since dysregulation of NF-κB is thought to be related to various diseases, it would be very important to elucidate its post-translational modifications and binding partners in detail and to deeply understand mechanisms of the NF-κB dysregulation. NF-κB p65 is known to interact with the basic transcription factor TFIID subunit hTAF31/TAF9 through the (Ф, hydrophobic amino acid; X, any amino acid) motif in a similar fashion to p53.

Analysis of an antioxidative defence system of hydrogen peroxide-treated pancreatic islet-derived 1.1B4 cells and siRNA targeting NR4A3-treated cells by microarray.

Pancreatic islet β-cells weaken under oxidative stress. In this study, human pancreatic islet-derived 1.1B4 cells were exposed to HO and analysed using a human microarray, which revealed that (, , , () and were upregulated, whereas and were not.

Analysis of the NUDT15 gene and metabolites of azathioprine in Japanese patients with inflammatory bowel disease.

Background: Thiopurines continue to play an important role in the treatment of inflammatory bowel disease (IBD). It is well known that thiopurines can cause several adverse reactions. Especially, hematopoietic toxicity may lead to severe agranulocytosis.

Effects of Hard Water Boiling on Chalky Rice in Terms of Texture Improvement and Ca Fortification.

In the present paper, we investigated the characteristics of chalky rice grains generated by ripening under high temperature and compared them with whole grains. We evaluated 14 unpolished rice grains harvested in Japan in 2021, and these samples (original grains) were divided into two groups (a whole grain group and a chalky grain one). We found that not only activities of endogenous amylase and proteinase, but also cell wall-degrading enzymes, such as xylanase and cellulase, changed markedly between chalky grains and whole grains.

Higher concentration of 25-hydroxycholesterol in treatment-naïve patients with type 2 diabetes compared to healthy individuals.

Background: Oxysterols are cholesterol oxidation derivatives with diverse biological activities. However, little is known about the oxysterol levels in treatment-naïve patients with type 2 diabetes.

Objective: We utilized gas chromatography-mass spectrometry to investigate the potential association between oxysterol concentrations and type 2 diabetes and atherosclerosis in treatment-naïve patients diagnosed with type 2 diabetes.

Differential regulation of ATP hydrolysis of RIG-I-like receptors by transactivation response RNA-binding protein.

Retinoic acid inducible gene (RIG)-I-like receptors (RLRs), including RIG-I, melanoma differentiation associated-5 (MDA5), and laboratory of genetics and physiology 2 (LGP2), play pivotal roles in viral RNA sensing to initiate antiviral interferon (IFN) responses. We previously reported that an RNA-silencing regulator, transactivation response RNA-binding protein (TRBP), up-regulates MDA5/LGP2-mediated IFN responses through interaction with LGP2. Here, we aimed to investigate the mechanism underlying the TRBP-mediated up-regulation of IFN response.

Metaplastic breast carcinoma producing prominent basal lamina with neuroendocrine differentiation: A case report.

Metaplastic breast carcinoma (MBC) is a heterogeneous group of invasive breast carcinomas (IBCs) characterized by the differentiation of the neoplastic epithelium toward squamous cells and/or mesenchymal-appearing elements. The present study describes the case of a 42-year-old woman who underwent a mastectomy and sentinel lymph node biopsy for two tumors in their left breast. One of the resected tumors was diagnosed as MBC with neuroendocrine (NE) differentiation and the other was diagnosed as IBC of no special type.

Isolation and physiological properties of methanogenic archaea that degrade tetramethylammonium hydroxide.

Tetramethylammonium hydroxide (TMAH) is a known toxic chemical used in the photolithography process of semiconductor photoelectronic processes. Significant amounts of wastewater containing TMAH are discharged from electronic industries. It is therefore attractive to apply anaerobic treatment to industrial wastewater containing TMAH.

Oral Administration of Lipopolysaccharide Enhances Insulin Signaling-Related Factors in the KK/Ay Mouse Model of Type 2 Diabetes Mellitus.

Lipopolysaccharide (LPS), an endotoxin, induces systemic inflammation by injection and is thought to be a causative agent of chronic inflammatory diseases, including type 2 diabetes mellitus (T2DM). However, our previous studies found that oral LPS administration does not exacerbate T2DM conditions in KK/Ay mice, which is the opposite of the response from LPS injection. Therefore, this study aims to confirm that oral LPS administration does not aggravate T2DM and to investigate the possible mechanisms.

Optimization of the CRISPR/Cas9 system using promoter derivatives in fission yeast.

The CRSIPR/Cas9 system has been applied to fission yeast, but there remain some rooms for improvement. Here we report that the weaker versions of the promoter, and promoters, for the potentially cytotoxic Cas9 achieved highly efficient mutagenesis and gene deletion at the locus. Employing a drug-selectable marker instead of conventional auxotrophic markers, our new vector system is compatible with a variety of experimental settings including prototrophic/auxotrophic strains and complete/minimal media.

Regulation of alanine racemase activity by carboxylates and the d-type substrate d-alanine.

Alanine racemases (ALRs) are essential for d-alanine (d-Ala) production in bacteria, and many ALRs have a conserved carbamylated lysine residue in the active site. Although short-chain carboxylates inhibit ALRs harbouring this lysine residue as substrate analogues, in an ALR variant with an alanine residue at this position, carboxylates behave as activators; however, this activation mechanism remains unclear. Here, we performed kinetic and structural analyses of U1ALR, an ALR from Latilactobacillus sakei UONUMA harbouring a glycine residue (Gly134) in the site of the carbamylated lysine residue.

Hypoxia-adapted Multiple Myeloma Stem Cells Resist γδ-T-Cell-mediated Killing by Modulating the Mevalonate Pathway.

Background/aim: The prognosis of patients with multiple myeloma (MM) has recently improved due to the emergence of new molecular targeting agents. However, MM remains incurable because MM stem cells are resistant to these agents. Therefore, it is essential to develop strategies to eradicate MM stem cells.

LsSpt23p is a regulator of triacylglycerol synthesis in the oleaginous yeast Lipomyces starkeyi.

The oleaginous yeast Lipomyces starkeyi has considerable potential in industrial application, since it can accumulate a large amount of triacylglycerol (TAG), which is produced from sugars under nitrogen limitation condition. However, the regulation of lipogenesis in L. starkeyi has not been investigated in depth.