Copy Number Analysis of 9p24.1 in Classic Hodgkin Lymphoma Arising in Immune Deficiency/Dysregulation.

A subset of patients with rheumatoid arthritis receiving methotrexate develop immune deficiencies and dysregulation-associated lymphoproliferative disorders. Patients with these disorders often exhibit spontaneous regression after MTX withdrawal; however, chemotherapeutic intervention is frequently required in patients with classic Hodgkin lymphoma arising in immune deficiency/dysregulation. In this study, we examined PD-L1 expression levels and 9p24.

New Dihydropyridine Derivative Attenuates NF-κB Activation via Suppression of Calcium Influx in a Mouse BV-2 Microglial Cell Line.

Activated microglia contribute to many neuroinflammatory diseases in the central nervous system. In this study, we attempted to identify an anti-inflammatory compound that could suppress microglial activation. We performed high-throughput screening with a chemical library developed at our institute.

Synthesis and Biological Evaluation of Lysophosphatidic Acid Analogues Using Conformational Restriction and Bioisosteric Replacement Strategies.

Lysophosphatidic acid (LPA) is a key player in many physiological and pathophysiological processes. The biological activities of LPA are mediated through interactions with-at least-six subtypes of G-protein-coupled receptors (GPCRs) named LPA. Developing a pharmacological tool molecule that activates LPA subtype receptors selectively will allow a better understanding of their specific physiological roles.

[Stereo-divergent Synthesis of Nonproteinogenic Amino Acids and Synthetic Study for Biologically Active Cyclopeptides].

Naturally occurring cyclopeptides are potential middle-molecule drug candidates beyond Lipinski's rule of five. This paper focuses on the structural determination and structure-activity relationship (SAR) study of two cyclopeptides: asperterrestide A and decatransin. The proposed asperterrestide A was synthesized by solution-phase peptide elongation, followed by macrolactamization.

Adaptability of the Sense of Agency in Healthy Young Adults in Sensorimotor Tasks for a Short Term.

Sense of agency (SoA) refers to the subjective feeling of controlling one's own actions and sensory feedback. The SoA occurs when the predicted feedback matches the actual sensory feedback and is responsible for maintaining behavioral comfort. However, sensorimotor deficits because of illness cause incongruence between prediction and feedback, so the patient loses comfort during actions.

Idiopathic Plasmacytic Lymphadenopathy Forms an Independent Subtype of Idiopathic Multicentric Castleman Disease.

Idiopathic multicentric Castleman disease (iMCD) is a type of Castleman disease that is not related to KSHV/HHV8 infection. Currently, iMCD is classified into iMCD-TAFRO (thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly) and iMCD-NOS (not otherwise specified). The former has been established as a relatively homogeneous disease unit that has been recently re-defined, while the latter is considered to be a heterogeneous disease that could be further divided into several subtypes.

Total Synthesis and Structural Determination of Cyclodepsipeptide Decatransin.

The structure determination of the 30-membered cyclodepsipeptide decatransin was demonstrated on the basis of total synthesis. Both ()- and ()-2-hydroxy-5-methylhexanoic acid derivatives were prepared via the Evans asymmetric alkylation. -Alkyl-enriched peptide fragments were synthesized by the Cbz strategy in the solution phase without formation of diketopiperazine and epimerization.

Blocking cholesterol efflux mechanism is a potential target for antilymphoma therapy.

Cholesterol is an essential plasma membrane lipid for the maintenance of cellular homeostasis and cancer cell proliferation. Free cholesterol is harmful to cells; therefore, excessive free cholesterol must be quickly esterified by acetyl-coenzyme A:cholesterol acetyltransferase (ACAT) and exported by scavenger receptor class B member I (SR-BI) or ATP-binding cassette protein A1 from specific cells such as macrophage foam cells, which contain cholesteryl ester-derived vacuoles. Many vacuoles are present in the cytoplasm of Burkitt lymphoma cells.

Idiopathic multicentric Castleman disease with positive antiphospholipid antibody: atypical and undiagnosed autoimmune disease?

Idiopathic multicentric Castleman disease (iMCD) is a systemic disorder characterized by systemic inflammation and organ dysfunction associated with an increase in pro-inflammatory cytokines. Some patients with iMCD are positive for autoantibodies, although their significance and relationship with specific associated autoimmune diseases are unclear. This study retrospectively analyzed the clinicopathological features of iMCD patients focusing on autoantibodies.

A Phenylfurocoumarin Derivative Reverses ABCG2-Mediated Multidrug Resistance In Vitro and In Vivo.

The ATP-binding cassette subfamily G member 2 (ABCG2) transporter is involved in the development of multidrug resistance in cancer patients. Many inhibitors of ABCG2 have been reported to enhance the chemosensitivity of cancer cells. However, none of these inhibitors are being used clinically.

Hydrolysis of Lignocellulosic Biomass in Hot-Compressed Water with Supercritical Carbon Dioxide.

This study investigated the decomposition behavior of bamboo under hydrothermal and hydrolysis conditions with HO/CO in a semicontinuous-flow reactor at 9.8 MPa. At 255 °C, with and without CO, xylan in bamboo completely decomposed into xylo-oligosaccharide (XOD).

Stereoselective Synthesis of 1-Aminocyclopropanecarboxylic Acid Carnosadines via Inter-intramolecular Double Alkylation with Optically Active 2-Methylaziridine Derivatives.

The stereoselective and short-step synthesis of -protected -carnosadine, -carnosadine, and carnosadine lactam was accomplished from a common cyclopropane intermediate. The inter-intramolecular double alkylation of diethyl malonate with an optically active 2-methylaziridine derivative gave the key cyclopropane in excellent yield and optical purity. The following monohydrolysis of the diester moiety using different reaction conditions provided both diastereomers of monoacids, which were converted to three carnosadine derivatives in 5-6 steps from the common diester.

Effects of a single dose of tablets containing lactononadecapeptide on cognitive function in healthy adults: a randomized, double-blind, cross-over, placebo-controlled trial.

Lactononadecapeptide (LNDP; NIPPLTQTPVVVPPFLQPE) is a memory-improving peptide. The current study aimed to determine the effects of a single dose of tablets containing LNDP on cognitive function in healthy Japanese men aged 30-59 years. A randomized, double-blind, cross-over, placebo-controlled trial was conducted in participants randomly assigned to receive LNDP or placebo tablets.

Gold-Catalyzed Amide/Carbamate-Linked ,-Acetal Formation with Bulky Amides and Alcohols.

A gold-catalyzed ,-acetal formation was established to construct an amide/carbamate-linked ,-acetal substructure with bulky alcohols. The acyliminium cation species generated from -alkynylbenzoic acid ester in the presence of a gold catalyst is highly reactive and underwent nucleophilic attack of various bulky alcohols and phenols at room temperature under neutral conditions, leading to the corresponding ,-acetals in yields of 34-89% with good functional group tolerance.

-Methylation of -adenosyl-L-Methionine Occurs Prior to Cyclopropanation in the Biosynthesis of 1-Amino-2-Methylcyclopropanecarboxylic Acid (Norcoronamic Acid) in a Bacterium.

Many pharmacologically important peptides are bacterial or fungal in origin and contain nonproteinogenic amino acid (NPA) building blocks. Recently, it was reported that, in bacteria, a cyclopropane-containing NPA 1-aminocyclopropanecarboxylic acid (ACC) is produced from the L-methionine moiety of -adenosyl-L-methionine (SAM) by non-canonical ACC-forming enzymes. On the other hand, it has been suggested that a monomethylated ACC analogue, 2-methyl-ACC (MeACC), is derived from L-valine.

Total Synthesis and Structural Revision of Cyclotetrapeptide Asperterrestide A.

The structural revision of cyclotetrapeptide asperterrestide A has been achieved based on total synthesis and molecular modeling. For these studies, (2 R,3 S)-MePhe(3-OH) and (2 S,3 S)-MePhe(3-OH) suitably protected for peptide synthesis were prepared via a stereoselective reduction of a ketone precursor derived from L- or d-serine, using L-selectride or DIBAL-H. The synthesis of the proposed structure of asperterrestide A (1a) was accomplished by solution-phase synthesis of a linear precursor followed by macrolactamization.

Antimicrobial resistance profiles of vancomycin-resistant species isolated from laboratory mice.

Isolates of 24 enterococci, 5 and 19 , possessing genes and showing low-level resistance to vancomycin were obtained from mice from commercial mouse breeding companies. Since some of these isolates showed resistance to other antibiotics, the purpose of this study was to clarify the resistant profiles of these isolates. One isolate showed resistance to erythromycin with a minimal inhibitory concentration (MIC) of 8 μg/mL and also showed apparent resistance to fluoroquinolones with an MIC of 32 μg/mL for ciprofloxacin.

Synthesis and biological evaluation of thielocin B1 analogues as protein-protein interaction inhibitors of PAC3 homodimer.

The synthesis and biological evaluation of thielocin B1 analogues have been demonstrated. Fourteen analogues modified in the central core and terminal carboxylic acid moiety were concisely synthesized by simple esterification or etherification reaction. The evaluation of synthetic analogues as inhibitors of proteasome assembling chaperone (PAC) complexes (the PAC3 homodimer and PAC1/PAC2) revealed that the natural product-like bending structure and terminal carboxylic acid groups were crucial for its biological activity.

Novel Potent ABCB1 Modulator, Phenethylisoquinoline Alkaloid, Reverses Multidrug Resistance in Cancer Cell.

ATP-binding cassette (ABC) transporters, which are concerned with the efflux of anticancer drugs from cancer cells, have a pivotal role in multidrug resistance (MDR). In particular, ABCB1 is a well-known ABC transporter that develops MDR in many cancer cells. Some ABCB1 modulators can reverse ABCB1-mediated MDR; however, no modulators with clinical efficacy have been approved.

Lactobacillus helveticus-fermented milk containing lactononadecapeptide (NIPPLTQTPVVVPPFLQPE) improves cognitive function in healthy middle-aged adults: a randomised, double-blind, placebo-controlled trial.

This study aimed to determine the effects of a Lactobacillus helveticus-fermented milk drink containing lactononadecapeptide (NIPPLTQTPVVVPPFLQPE) on the cognitive function of healthy middle-aged adults. A randomised, double-blind controlled study was conducted in healthy participants who were randomly assigned to receive a L. helveticus-fermented milk drink (190 g/day) or the equivalent amount of a placebo drink once a day for eight weeks.

Identification of peptides present in sour milk whey that ameliorate scopolamine-induced memory impairment in mice.

Cognitive impairment is treated with cholinesterase inhibitors that slow cognitive decline but cause significant adverse effects. Functional foods that improve memory without such effects would therefore be valuable. We reported that unidentified components of sour milk whey produced by fermentations using Lactobacillus helveticus and Saccharomyces cerevisiae improved memory in a mouse model of scopolamine-induced memory impairment.

Invasive mucinous adenocarcinoma of the lung presenting as a large, thin-walled cyst: A case report and literature review.

Invasive mucinous adenocarcinoma (IMA), formerly referred to as mucinous bronchioloalveolar carcinoma, is a rare variant form of invasive adenocarcinoma and is radiologically characterized by dense pneumonic consolidation, ground-glass opacity and nodules. By contrast, large, thin-walled cysts are rare. We herein report the case of a 75-year-old man with IMA presenting as a large, irregularly shaped cystic lesion.

Hemoperitoneum Secondary to Rupture of a Hepatic Metastasis from Small Cell Lung Cancer during Chemotherapy: A Case with a Literature Review.

A 65-year-old man was diagnosed with small cell lung cancer with multiple liver metastases. Three days after initiating chemotherapy, he experienced abdominal discomfort with hypotension. Computed tomography revealed a ruptured liver metastasis and the presence of hemorrhagic ascites.

Difference of two new LCMV strains in lethality and viral genome load in tissues.

More than 30 strains of lymphocytic choriomeningitis virus (LCMV) have been isolated from mice, hamsters and humans in the United States, Europe and Japan. Experimentally infected mice exhibit different clinical signs and lethality depending on a combination of LCMV epitope peptides and host major histocompatibility complex (MHC) class I molecules. This study examined the pathogenicity, clinical signs and lethality, of two new LCMV strains (BRC and OQ28) using three inbred mouse strains with different genetic backgrounds having different H-2D haplotypes.

Discovery of Novel Cinchona-Alkaloid-Inspired Oxazatwistane Autophagy Inhibitors.

The cinchona alkaloids are a privileged class of natural products and are endowed with diverse bioactivities. However, for compounds with the closely-related oxazatricyclo[4.4.