Bone morphogenetic protein 4 induces hematopoietic stem cell development from murine hemogenic endothelial cells in culture.

Hematopoietic stem cells (HSCs) develop from hemogenic endothelial cells (HECs) during mouse embryogenesis. Understanding the signaling molecules required for HSC development is crucial for the in vitro derivation of HSCs. We previously induced HSCs from embryonic HECs, isolated at embryonic day 10.

Transition of signal requirement in hematopoietic stem cell development from hemogenic endothelial cells.

Hematopoietic stem cells (HSCs) develop from hemogenic endothelial cells (HECs) in vivo during mouse embryogenesis. When cultured in vitro, cells from the embryo phenotypically defined as pre-HSC-I and pre-HSC-II have the potential to differentiate into HSCs. However, minimal factors required for HSC induction from HECs have not yet been determined.

Aromatic border plants in early season berries do not increase parasitism of spotted wing drosophila, Drosophila suzukii.

Background: The spotted wing drosophila, Drosophila suzukii Matsumura, is a South-East Asian vinegar fly that is a serious worldwide economic threat to the small fruit industry. Typical control consists of weekly pesticide applications, which can have nontarget effects, increase residual pesticides and lead to the development of resistance within pest populations. One potential alternate method of control is the planting of aromatic intercrops to attract the natural enemies of D.

Adventive Larval Parasitoids Reconstruct Their Close Association with Spotted-Wing Drosophila in the Invaded North American Range.

Two species of larval parasitoids of the globally invasive fruit pest, Drosophila suzukii (Diptera: Drosophilidae), Leptopilina japonica, and Ganaspis brasiliensis (both Hymenoptera: Figitidae), were detected in British Columbia, Canada in 2016 and 2019, respectively. Both are presumed to have been unintentionally introduced from Asia; however, the extent of their establishment across different habitats with diverse host plants used by D. suzukii was unclear.

Hematopoietic Stem Cell-Independent Differentiation of Mast Cells From Mouse Intraembryonic VE-Cadherin+ Cells.

Hematopoietic stem cell (HSC)-independent hematopoiesis from hemogenic endothelial cells (HECs) in the mouse embryo has been recognized as a source of tissue-resident hematopoietic cells in adult mice. Connective tissue mast cells (MCs) have been reported to originate from VE-cadherin (VE-cad)-expressing HECs in the yolk sac and embryo proper (EP) by a VE-cad-Cre-mediated lineage-tracing analysis. However, it remains unclear whether MCs are generated via a conventional HSC-dependent hematopoietic differentiation pathway, or whether through a fast-track pathway bypassing the emergence of HSCs.

Bone morphogenetic protein 4 differently promotes distinct VE-cadherin precursor stages during the definitive hematopoietic development from embryonic stem cell-derived mesodermal cells.

Definitive hematopoietic cells develop from fetal liver kinase 1 (Flk1) mesodermal cells during the in vitro differentiation of mouse embryonic stem cells (ESCs). VE-cadherinCD41CD45(V4145) hemogenic endothelial cells (HECs) and VE-cadherinCD41CD45 (V4145) cells mediate the definitive hematopoietic development from Flk1 cells. Bone morphogenetic protein 4 (BMP4) is known to be essential for the formation of mesoderm.

EHHADH contributes to cisplatin resistance through regulation by tumor-suppressive microRNAs in bladder cancer.

Background: Cisplatin-based chemotherapy is recommended as the primary treatment for advanced bladder cancer (BC) with unresectable or metastatic disease. However, the benefits are limited due to the acquisition of drug resistance. The mechanisms of resistance remain unclear.

Targeting NPL4 via drug repositioning using disulfiram for the treatment of clear cell renal cell carcinoma.

The alcohol-abuse drug disulfiram has antitumor effects against diverse cancer types via inhibition of the ubiquitin-proteasome protein nuclear protein localization protein 4 (NPL4). However, the antitumor effects of NPL4 and disulfiram in clear cell renal cell carcinoma (ccRCC) are unclear. Here, we evaluated the therapeutic potential of targeting the ubiquitin-proteasome pathway using disulfiram and RNA interference and investigated the mechanisms underlying disulfiram in ccRCC.

Characterization of PHGDH expression in bladder cancer: potential targeting therapy with gemcitabine/cisplatin and the contribution of promoter DNA hypomethylation.

d-3-Phosphoglycerate dehydrogenase (PHGDH) conducts an important step in the synthesis of serine. Importantly, the PHGDH gene is often amplified in certain cancers. Our previous studies revealed that PHGDH gene amplification was associated with poor overall survival in clear cell renal cell carcinoma (ccRCC) and that metabolic reprogramming of serine synthesis through PHGDH recruitment allowed ccRCC cells to survive in unfavorable environments.

Oncogenic effects of RAB27B through exosome independent function in renal cell carcinoma including sunitinib-resistant.

Exosomes are 40-100 nm nano-sized extracellular vesicles. They are released from many cell types and move into the extracellular space, thereby transferring their components to recipient cells. Exosomes are receiving increasing attention as novel structures participating in intracellular communication.

Potential new therapy of Rapalink-1, a new generation mammalian target of rapamycin inhibitor, against sunitinib-resistant renal cell carcinoma.

Sunitinib, a multitargeted receptor tyrosine kinase inhibitor including vascular endothelial growth factor, has been widely used as a first-line treatment against metastatic renal cell carcinoma (mRCC). However, mRCC often acquires resistance to sunitinib, rendering it difficult to treat with this agent. Recently, Rapalink-1, a drug that links rapamycin and the mTOR kinase inhibitor MLN0128, has been developed with excellent therapeutic effects against breast cancer cells carrying mTOR resistance mutations.

[Human T-lymphotropic virus type 1 uveitis in children].

We report here five pediatric patients with human T-lymphotropic virus type 1 (HTLV-I) uveitis. The patients were one boy and four girls aged between 3 and 14 years. The transmission route was considered to be breast feeding from their mothers.

[Synthesis, pharmacological activity and biopharmaceutical characteristics of alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetates].

The pro-drugs of alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetic acid(I) with a potent anti-inflammatory activity were synthesized in order to reduce its gastrointestinal side effects. Various esters synthesized were evaluated for their anti-inflammatory activity and ulcerogenicity. Among the compounds maintaining a potent activity of I, N,N-dimethylcarbamoylmethyl alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetate (II-18) showed excellent biopharmaceutical characteristics.

[Pharmacokinetics of sodium 4-[alpha-hydroxy-5-(1-imidazolyl)-2-methylbenzyl]-3,5-dimethylbenzoate (Y-20811), a new thromboxane synthetase inhibitor. I. Isolation and structure elucidation of urinary metabolite in dog].

The urinary metabolites of sodium 4-[alpha-hydroxy-5-(1-imidazolyl)-2-methylbenzyl]-3,5-dimethylbenzoat e (Y-20811) in dog were investigated. The main metabolite was isolated by high performance liquid chromatography and subsequent preparative thin layer chromatography. The structure of this metabolite was established as 4-[alpha-hydroxy-2-hydroxymethyl-5-(1-imidazolyl)benzyl]-3,5- dimethylbenzoic acid on the basis of spectral analyses and confirmed by its total synthesis.

[Thromboxane synthetase inhibitors. I. Synthesis of some imidazolylarylmethanols and their inhibitory activity on platelet aggregation].

Several imidazolylpyridinemethanols and imidazolylbenzenemethanols were prepared and evaluated for an inhibitory activity against arachidonic acid-induced platelet aggregation. The result shows that the arylmethanol moiety is essential for the activity and may correspond to the 15-OH group of prostagrandin H2 (PGH2). Among the compounds tested, 4-[alpha-hydroxy-5-(1-imidazolyl)-2-methylbenzyl]-3,5-dimethylbenzoic acid (XV) was found to have a potent inhibitory activity and a long duration of action.

[Thromboxane synthetase inhibitors. II. Optical resolution of 4-[alpha-hydroxy-5-(1-imidazolyl)-2-methylbenzyl]-3,5-dimethylbenzo ic acid].

The optical resolution of racemic 4-[alpha-hydroxy-5-(1-imidazolyl)-2-methylbenzyl]-3,5-dimethylbenzoic acid (dl-I), a new potent and long lasting thromboxane synthetase inhibitor, was investigated. (S)-3-(3,5-Dinitrobenzoylthio)-2-methylpropionyl group was introduced to alpha-hydroxy moiety of methyl ester of dl-I by three steps of reaction to give the corresponding ester compound (VIa). Then, two diastereomers of VIa, alpha-VIa and beta-VIa, were separated by column chromatography using on silica gel.