Immunotherapy-induced reprogramming of cancer-associated fibroblasts can promote tumor progression.

Use of immune checkpoint inhibitors (ICIs) as cancer immunotherapy has advanced rapidly in the clinic; however, ICI initiation can also cause an unexpectedly rapid acceleration of cancer progression in some patients. Here, we used a murine syngeneic melanoma model to conduct mechanistic analysis of cancer-associated fibroblast (CAF) function in cancer progression in the context of immunotherapy. We found that after ICI treatment CAFs acquire inflammatory properties, which can promote tumor progression.

The Discovery of Membrane Vesicle Biogenesis in the Polyhydroxybutyrate-non-producing Mutant Strain of Cupriavidus necator H16.

Extracellular membrane vesicles (MVs) caused by the artificial production of polyhydroxybutyrate (PHB) were previously detected in Escherichia coli. We herein observed MV biogenesis in the mutant strain (-PHB) of the natural PHB producer, Cupriavidus necator H16. This inverse relationship was revealed through comparative electron microscopic ana-lyses of wild-type and mutant strains.

Structural diversity of decalin forming Diels-Alderase.

The Diels-Alder (DA) reaction, specifically referring to the [4 + 2] cycloaddition reaction in pericyclic reactions, is a process that forms two carbon-carbon covalent bonds in a single step via an electron ring transition state. Among the secondary metabolites produced by microorganisms, numerous compounds are biosynthesized through DA reactions, most of which are enzymatic. Our research group has discovered an enzyme named Diels-Alderase (DAase) that catalyzes the DA reaction in filamentous fungi, and we have been investigating its catalytic mechanism.

Taxonomic characterization of Sphaerotilus microaerophilus sp. nov., a sheath-forming microaerophilic bacterium of activated sludge origin.

A microaerophilic Gram-stain-negative bacilliform bacterial strain, FB-5, was isolated from activated sludge in Yokohama, Japan, that exhibited filamentous growth and formed a microtube (sheath). Cells were motile using a single polar flagellum. The optimum growth temperature and pH were 30 °C and 7.

Structural and Functional Analyses of Inhibition of Human Dihydroorotate Dehydrogenase by Antiviral Furocoumavirin.

Natural products are important sources of seed compounds for drug discovery. However, it has become difficult in recent years to discover new compounds with valuable pharmacological activities. On the other hand, among the vast number of natural products that have been isolated so far, a considerable number of compounds with specific biological activities are thought to be overlooked in screening that uses biological activity as an index.

Tumor stroma-derived ANGPTL2 potentiates immune checkpoint inhibitor efficacy.

Use of immune checkpoint inhibitors (ICIs) as cancer immunotherapy has advanced rapidly in the clinic. We recently reported that tumor stroma-derived angiopoietin-like protein 2 (ANGPTL2) has tumor suppressive activity by enhancing dendritic cell-mediated CD8 T cell anti-tumor immune responses. However, a direct impact of ANGPTL2 on ICI anti-tumor effect remains unclear.

Uncommon Arrangement of Self-resistance Allows Biosynthesis of de novo Purine Biosynthesis Inhibitor that Acts as an Immunosuppressor.

(-)-FR901483 () isolated from the fungus sp. No.11231 achieves immunosuppression via nucleic acid biosynthesis inhibition rather than IL-2 production inhibition as accomplished by FK506 and cyclosporin A.

Efficacy and safety in mice of repeated, lifelong administration of an ANGPTL3 vaccine.

Previously, we reported that an ANGPTL3 vaccine is a hopeful therapeutic option against dyslipidemia. In our current study, we assess durability and booster effects of that vaccine over a period representing a mouse's lifespan. The vaccine remained effective for over one year, and booster vaccination maintained suppression of circulating triglyceride levels thereafter without major adverse effects on lungs, kidneys, or liver, suggesting vaccine efficacy and safety.

Bacterial Population Changes during the Degradation Process of a Lactate (LA)-Enriched Biodegradable Polymer in River Water: LA-Cluster Preferable Bacterial Consortium.

The lactate-based polyester poly[lactate (LA)--3-hydroxybutyrate (3HB)], termed LAHB, is a highly transparent and flexible bio-based polymeric material. There are many unknowns regarding its degradation process in riverine environments, especially the changes in bacterial flora that might result from its degradation and the identities of any LAHB-degrading bacteria. LAHB were immersed in the river water samples (A and B), and LAHB degradation was observed in terms of the weight change of the polymer and the microscopic changes on the polymer surfaces.

ANGPTL2 promotes immune checkpoint inhibitor-related murine autoimmune myocarditis.

Use of immune checkpoint inhibitors (ICIs) as cancer immunotherapy advances rapidly in the clinic. Despite their therapeutic benefits, ICIs can cause clinically significant immune-related adverse events (irAEs), including myocarditis. However, the cellular and molecular mechanisms regulating irAE remain unclear.

Biosynthesis of Polycyclic Natural Products from Conjugated Polyenes via Tandem Isomerization and Pericyclic Reactions.

We report biosynthetic pathways that can synthesize and transform conjugated octaenes and nonaenes to complex natural products. The biosynthesis of (-)-PF1018 involves an enzyme PfB that can control the regio-, stereo-, and periselectivity of multiple reactions starting from a conjugated octaene. Using PfB as a lead, we discovered a homologous enzyme, BruB, that facilitates diene isomerization, tandem 8π-6π-electrocyclization, and a 1,2-divinylcyclobutane Cope rearrangement to generate a new-to-nature compound.

Non-target GC-MS analyses of fecal VOCs in NASH-hepatocellular carcinoma model STAM mice.

The increased incidence of obesity in the global population has increased the risk of several chronic inflammation-related diseases, including non-alcoholic steatohepatitis (NASH)-hepatocellular carcinoma (HCC). The progression from NASH to HCC involves a virus-independent liver carcinogenic mechanism; however, we currently lack effective treatment and prevention strategies. Several reports have suggested that fecal volatile organic compounds (VOCs) are strongly associated with NASH-HCC; therefore, we explored the biomarkers involved in its pathogenesis and progression.

Plasma ANGPTL8 Levels and Risk for Secondary Cardiovascular Events in Japanese Patients With Stable Coronary Artery Disease Receiving Statin Therapy.

Background: The ability to predict secondary cardiovascular events could improve health of patients undergoing statin treatment. Circulating ANGPTL8 (angiopoietin-like protein 8) levels, which positively correlate with proatherosclerotic lipid profiles, activate the pivotal proatherosclerotic factor ANGPTL3. Here, we assessed potential association between circulating ANGPTL8 levels and risk of secondary cardiovascular events in statin-treated patients.

Screening method toward ClbP-specific inhibitors.

Background: Colibactin is a genotoxin produced by Escherichia coli and other Enterobacteriaceae that is believed to increase the risk of colorectal cancer (CRC) of their symbiosis hosts, including human. A peptidase ClbP is the key enzyme for activation of colibactin. Inhibition of ClbP is considered to impede maturation of precolibactin into genotoxic colibactin.

Biosynthetic Gene Expression and Tissue Distribution of Diosgenin in .

Diosgenin is an aglycone of dioscin, a major bioactive steroidal saponin found in plants, including Himalayan Paris (), fenugreek (), and yam ( spp.). We have previously demonstrated that a species of natural yam, , contains a promising bioactive compound diosgenin, which induces anti-carcinogenic and anti-hypertriacylglycerolemic activities.

Increased numbers of pre-operative circulating monocytes predict risk of developing cardiac surgery-associated acute kidney injury in conditions requiring cardio pulmonary bypass.

Background: Evaluating patients' risk for acute kidney injury (AKI) is crucial for positive outcomes following cardiac surgery. Our aims were first to select candidate risk factors from pre- or intra-operative real-world parameters collected from routine medical care and then evaluate potential associations between those parameters and risk of onset of post-operative cardiac surgery-associated AKI (CSA-AKI).

Method: We conducted two cohort studies in Japan.

Tumor cell-derived ANGPTL2 promotes β-catenin-driven intestinal tumorigenesis.

Uncontrolled proliferation of intestinal epithelial cells caused by mutations in genes of the WNT/β-catenin pathway is associated with development of intestinal cancers. We previously reported that intestinal stromal cell-derived angiopoietin-like protein 2 (ANGPTL2) controls epithelial regeneration and intestinal immune responses. However, the role of tumor cell-derived ANGPTL2 in intestinal tumorigenesis remained unclear.

Advancing the Biosynthetic and Chemical Understanding of the Carcinogenic Risk Factor Colibactin and Its Producers.

Recent studies have shown that often carries a biosynthetic gene cluster termed either the island or the cluster that allows the production of a genotoxic polyketide-nonribosomal peptide hybrid secondary metabolite called colibactin. While the gene cluster is not always expressed, when the strain that resides in the colon produces the genotoxin, it is suspected to become a risk factor for colorectal cancer. Therefore, there is great interest in devising a simple method for the detection of colibactin-producing strains and understanding the detailed mechanism of how colibactin can induce oncogenesis, to develop convenient early screening methods and possible preventive treatments against colorectal cancer.

Combined thoracoscopic and axillary subcutaneous endoscopic thyroidectomy: a novel approach for cervicomediastinal goiters.

Purpose: After our group described the first remote-access thyroidectomy series in 2000, the procedure has been further developed. Although a thoracoscopic approach with a conventional open cervical incision for thyroid goiters with mediastinal extension has been performed at many institutions, remote-access thyroidectomy for cervicomediastinal goiters has not been established. We have performed combined thoracoscopic and axillary subcutaneous endoscopic thyroidectomies (axillo-thoracic endoscopic thyroidectomies).

Recent advances in the chemo-biological characterization of decalin natural products and unraveling of the workings of Diels-Alderases.

The Diels-Alder (DA) reaction refers to a [4 + 2] cycloaddition reaction that falls under the category of pericyclic reactions. It is a reaction that allows regio- and stereo-selective construction of two carbon-carbon bonds simultaneously in a concerted manner to generate a six-membered ring structure through a six-electron cyclic transition state. The DA reaction is one of the most widely applied reactions in organic synthesis, yet its role in biological systems has been debated intensely over the last four decades.