Isolation, structural elucidation and biosynthetic pathway of bioactive prenyl quinone compounds from Panus lecomtei based on untargeted metabolomics combined with molecular networking.

Panus lecomtei is a relatively unfamiliar and undeveloped mushroom. This study generated ethyl acetate extracts of P. lecomtei intracellular (I), extracellular (E) and total fermentation broth (T).

Alkaline ceramidase 1-mediated platelet ceramide catabolism mitigates vascular inflammation and abdominal aortic aneurysm formation.

Abdominal aortic aneurysm (AAA) is a highly lethal vascular disease. The role of platelets in AAA remains incompletely understood. Here we show that platelet ceramides, rather than other phospholipids, were elevated in an angiotensin II (AngII)-induced AAA murine model and in patients with AAA by using targeted lipidomic analysis.

The Protective Effects of Active Peptide GLP4 on Lung Injury Induced by Cadmium Poisoning in Mice.

triterpenes and spore powder have shown promising results in mitigating cadmium-induced renal and hepatic injuries. active peptide GLP4 is a natural protein with dual antioxidant activities derived from the mycelium of . However, its efficacy in alleviating cadmium-induced lung injury remains unexplored.

Targeting cytokine-like protein FAM3D lowers blood pressure in hypertension.

Current antihypertensive options still incompletely control blood pressure, suggesting the existence of uncovered pathogenic mechanisms. Here, whether cytokine-like protein family with sequence similarity 3, member D (FAM3D) is involved in hypertension etiology is evaluated. A case-control study exhibits that FAM3D is elevated in patients with hypertension, with a positive association with odds of hypertension.

Experimental determination of surface energy for high-energy surface: A review.

The experimental determination of surface free energy is of great importance for engineering applications. However, there is no universal, reliable, and convenient measurement means to achieve experimental determination of solid surface energy for high-energy surface. In this work, the existing techniques for experimental determination of surface energy of solids, including indirect (4 kinds) and direct methods (3 kinds), were critically reviewed.

Activin Receptor-Like Kinase 3 Directly Couples Gαq (Guanine Nucleotide-Binding Protein Subunit αq)/ Gαq (Guanine Nucleotide-Binding Protein Subunit α11) to Regulate Vascular Contractility.

Background: Vascular smooth muscle cell (VSMC) contractility is critical for blood pressure regulation and vascular homeostasis. Identifying the key molecule that maintains VSMC contractility may provide a novel therapeutic target for vascular remodeling. ALK3 (activin receptor-like kinase 3) is a serine/threonine kinase receptor, and deletion of ALK3 causes embryonic lethality.

Predicting bleeding risk in a Chinese immune thrombocytopenia (ITP) population: development and assessment of a new predictive nomogram.

The aim of this study was to develop a model that could be used to forecast the bleeding risk of ITP based on proinflammatory and anti-inflammatory factors. One hundred ITP patients were recruited to build a new predictive nomogram, another eighty-eight ITP patients were enrolled as validation cohort, and data were collected from January 2016 to January 2019. Four demographic characteristics and fifteen clinical characteristics were taken into account.

Ruxolitinib-based combinations in the treatment of myelofibrosis: worth looking forward to.

Ruxolitinib is a targeted drug to treat myelofibrosis (MF). Ruxolitinib has significant advantages in spleen reduction and increasing 5-year overall survival (OS), and ruxolitinib-based combinations might provide more benefits than ruxolitinib monotherapy. In this review, we focus on the data of ruxolitinib-based combinations therapies and treatment-related adverse events (AEs) and safety.

Elucidation of the Mechanisms and Molecular Targets of Yiqi Shexue Formula for Treatment of Primary Immune Thrombocytopenia Based on Network Pharmacology.

Yiqi Shexue formula (YQSX) is traditionally used to treat primary immune thrombocytopenia (ITP) in clinical practice of traditional Chinese medicine. However, its mechanisms of action and molecular targets for treatment of ITP are not clear. The active compounds of YQSX were collected and their targets were identified.

Relation of Blood Arsenic Concentration with Effect and Safety of Arsenic-Containing Qinghuang Powder () in Patients with Myelodysplastic Syndrome.

Objective: To investigate the relation of blood arsenic concentration (BAC) with clinical effect and safety of arsenic-containing Qinghuang Powder (, QHP) in patients with myelodysplastic syndrome (MDS).

Methods: Totally 163 patients with MDS were orally treated with QHP for 2 courses of treatment, 3 months as 1 course. The BACs of patients were detected by atomic fluorescence spectrophotometry at 1, 3, and 6 months during the treatment, and the effective rate, hematological improvement and safety in patients after treatment with QHP were analyzed.

[Level of Regulatory B Cells in Patients with Immune Thrombocytopenia and Its Clinical Significance].

Objective: To investigate the role of regulatory B cells (Breg) in pathogenesis of immune thrombocytopenia(ITP) and its clinical significance.

Methods: A total of 40 ITP patients and 20 normal controls were enrolled in this study. The content of Breg, Th1, Th2, Th17 and Treg cells were detected by flow cytometry (FCM).

[Secretory Imbalance between Pro-inflammatory and Anti-inflammatory Cytokines in the Patients with Immune Thrombocytopenia].

Objective: To analyze the imbalance of pro-inflammatory and anti-inflammatory cytokines in the patients of immune thrombocytopenia (ITP).

Methods: Thirty-five patients with ITP were enrolled in ITP group, while 28 healthy persons were included in control group. The expressions of IL-8, IL-17A, IL-22, TNF-α, IFN-γ, IL-4, CD40, CD40L, TGF-β and IL-10 were detected by flow cytometry with aimPlex multiple immunoassay Flow.

Study on the Clinical Safe and Effective Methods of Arsenic-Containing Compound-Qinghuang Powder in the Treatment of Myelodysplastic Syndrome.

Objective: To establish the clinical safe and effective methods of arsenic-containing compound-Qinghuang Powder (compound-QHP) in the treatment of myelodysplastic syndrome (MDS).

Methods: 200 patients with MDS were treated with compound-QHP (daily dose of 0.1 g realgar).

Macrocyclic prolinyl acyl guanidines as inhibitors of β-secretase (BACE).

The synthesis, evaluation, and structure-activity relationships of a class of acyl guanidines which inhibit the BACE-1 enzyme are presented. The prolinyl acyl guanidine chemotype (7c), unlike compounds of the parent isothiazole chemotype (1), yielded compounds with good agreement between their enzymatic and cellular potency as well as a reduced susceptibility to P-gp efflux. Further improvements in potency and P-gp ratio were realized via a macrocyclization strategy.

Acyl guanidine inhibitors of β-secretase (BACE-1): optimization of a micromolar hit to a nanomolar lead via iterative solid- and solution-phase library synthesis.

This report describes the discovery and optimization of a BACE-1 inhibitor series containing an unusual acyl guanidine chemotype that was originally synthesized as part of a 6041-membered solid-phase library. The synthesis of multiple follow-up solid- and solution-phase libraries facilitated the optimization of the original micromolar hit into a single-digit nanomolar BACE-1 inhibitor in both radioligand binding and cell-based functional assay formats. The X-ray structure of representative inhibitors bound to BACE-1 revealed a number of key ligand:protein interactions, including a hydrogen bond between the side chain amide of flap residue Gln73 and the acyl guanidine carbonyl group, and a cation-π interaction between Arg235 and the isothiazole 4-methoxyphenyl substituent.

Inhibition of influenza virus replication via small molecules that induce the formation of higher-order nucleoprotein oligomers.

Influenza nucleoprotein (NP) plays multiple roles in the virus life cycle, including an essential function in viral replication as an integral component of the ribonucleoprotein complex, associating with viral RNA and polymerase within the viral core. The multifunctional nature of NP makes it an attractive target for antiviral intervention, and inhibitors targeting this protein have recently been reported. In a parallel effort, we discovered a structurally similar series of influenza replication inhibitors and show that they interfere with NP-dependent processes via formation of higher-order NP oligomers.

Small molecule receptor protein tyrosine phosphatase γ (RPTPγ) ligands that inhibit phosphatase activity via perturbation of the tryptophan-proline-aspartate (WPD) loop.

Protein tyrosine phosphatases (PTPs) catalyze the dephosphorylation of tyrosine residues, a process that involves a conserved tryptophan-proline-aspartate (WPD) loop in catalysis. In previously determined structures of PTPs, the WPD-loop has been observed in either an "open" conformation or a "closed" conformation. In the current work, X-ray structures of the catalytic domain of receptor-like protein tyrosine phosphatase γ (RPTPγ) revealed a ligand-induced "superopen" conformation not previously reported for PTPs.

Solid-phase synthesis of a library based on biphenyl-containing trypsin-like serine protease inhibitors.

The solid-phase synthesis of a library based on an unusual biphenyl-containing trypsin-like serine protease inhibitor is described. Key to this effort was the synthesis of a highly functionalized aryl boronic acid reagent which required the development of a novel and efficient method to convert a triflate to a pinacolboronate in large scale.

Solid-phase synthesis and anti-infective activity of a combinatorial library based on the natural product anisomycin.

The solid-phase synthesis of a library based on the natural product anisomycin is described. The resulting library was tested against a panel of bacterial and fungal targets, and active compounds were identified in a Staphylococcus aureus whole-cell assay and an efflux-deficient fungal whole-cell assay.