The m6A methyltransferase METTL14 promotes oncogenic Kras induced juvenile myelomonocytic leukemia through dysregulating autophagy.

The N6-methyladenosine (m6A) modification plays an important role in the pathogenesis of various myeloid malignancies. However, its specific role in RAS mutation-induced myeloid malignancy is incompletely understood. In this study, we found that m6A methyltransferase methyltransferase-like 14 (METTL14) was highly expressed and associated with a shorter survival in a RAS-mutation myeloid malignancy, juvenile myelomonocytic leukemia (JMML).

Icaritin Attenuates HSC Activation by Down-regulating the HIF-1α and TGF-β/Smad Signaling Pathways to Ameliorate Liver Fibrosis.

Introduction: Icaritin is a bioactive flavonol isolated from the Chinese medicinal herb Epimedium. The comprehensive understanding of antifibrotic effects and associated molecular mechanisms of icaritin remains incomplete. This study aims to explore the protective effects of icaritin against liver fibrosis and to further elucidate the mechanisms involved.

Mechanical Force-Induced cGAS Activation in Carcinoma Cells Facilitates Splenocytes into Liver to Drive Metastasis.

Liver metastasis is the main cause of cancer-related mortality. During the metastasis process, circulating carcinoma cells hardly pass through narrow capillaries, leading to nuclear deformation. However, the effects of nuclear deformation and its underlying mechanisms on metastasis need further study.

A regio-specific 4--methyltransferase from regiospecifically catalyzing 8-prenylkeampferol to icaritin.

is widely used in traditional Chinese medicine and contains rich bioactive compounds. These compounds often have a methyl group at their 4'-OH position catalyzed by methyltransferases. Therefore, studying methyltransferases in plants is of great significance.

Enzymatic synthesis of anhydroicaritin, baohuoside and icariin.

Anhydroicaritin (), baohuoside () and icariin () were recognized as major pharmacologically active ingredients of plants. Their primary means of acquisition were chemical isolation from plants. However, it suffers from low yield, environmental pollution and shortage of plants.

Improvement of human platelet aggregation post-splenectomy with paraesophagogastric devascularization in chronic hepatitis B patients with cirrhotic hypersplenism.

Thrombocytopenia is a common hematological abnormality in patients with cirrhotic hypersplenism. Splenectomy with paraesophagogastric devascularization (SPD) is a conventional surgical therapy which can reverse pancytopenia in these patients. Platelets are traditionally recognized for their central role in hemostasis.

Ep7GT, a glycosyltransferase with sugar donor flexibility from Epimedium pseudowushanense, catalyzes the 7-O-glycosylation of baohuoside.

Icariin (1a), a 7-O-glycosylated flavonoid glycoside, is recognized as the major pharmacologically active ingredient of Epimedium plants, which have been used in traditional Chinese medicine for thousands of years. However, no glycosyltransferase (GT) responsible for the 7-O-glycosylation of flavonoids has been identified from Epimedium plants to date. Herein, a GT, Ep7GT, was identified from E.

A regiospecific rhamnosyltransferase from Epimedium pseudowushanense catalyzes the 3-O-rhamnosylation of prenylflavonols.

Epimedium is used in traditional Chinese medicine and contains flavonol glycosides that exhibit multiple biological activities. These bioactive flavonol glycosides usually have a rhamnose moiety at the 3-OH position of prenylflavonols, such as icariin (9), baohuoside I (1a) and baohuoside II (2a). However, to date, no rhamnosyltransferase has been reported to catalyze the 3-O-rhamnosylation of prenylflavonols.

Two Furanharzianones with 4/7/5/6/5 Ring System from Microbial Transformation of Harzianone.

Furanharzianones A and B (2 and 3), two new harziane-type diterpenoids with a tetrahydrofuran and unusual 4/7/5/6/5 ring system, were obtained from the microbial transformation of harzianone (1) by a bacterial strain Bacillus sp. IMM-006. The structures, including the stereochemistry, of the two new compounds were elucidated by extensive spectroscopic analysis.

Molecular insights into the enzyme promiscuity of an aromatic prenyltransferase.

Aromatic prenyltransferases (aPTases) transfer prenyl moieties from isoprenoid donors to various aromatic acceptors, some of which have the rare property of extreme enzymatic promiscuity toward both a variety of prenyl donors and a large diversity of acceptors. In this study, we discovered a new aPTase, AtaPT, from Aspergillus terreus that exhibits unprecedented promiscuity toward diverse aromatic acceptors and prenyl donors and also yields products with a range of prenylation patterns. Systematic crystallographic studies revealed various discrete conformations for ligand binding with donor-dependent acceptor specificity and multiple binding sites within a spacious hydrophobic substrate-binding pocket.

Neural anti-inflammatory sesquiterpenoids from the endophytic fungus Trichoderma sp. Xy24.

Three new sesquiterpenoids trichoacorenols B-C and cyclonerodiol B (1-3), along with three known ones (4-6), were isolated from the mangrove plant endophytic fungus Trichoderma sp. Xy24 using various column chromatography techniques. The structures of these compounds were determined on the basis of extensive spectroscopic data analyses.

Flavonoids from the cultured cells of Glycyrrhiza uralensis.

Two new flavonoids (1 and 2), along with 14 known ones (3-16), were isolated from the cultured cells of Glycyrrhiza uralensis. Most of them were prenylated flavonoids. Their structures were elucidated on the basis of spectroscopic data analysis.