Fibrinogen is Associated with Clinical Adverse Events in Patients with Psoriasis and Coronary Artery Disease.

Purpose: The presence of elevated fibrinogen levels is associated with cardiovascular disease. However, whether fibrinogen level is associated with adverse clinical events in patients with psoriasis and coronary artery disease (CAD) is unknown. This study aimed to investigate the relationship between fibrinogen levels and cardiovascular adverse events in these patients.

Lipoprotein(a) is a new prognostic factor in patients with psoriasis and coronary artery disease: a retrospective cohort study.

Background: The prognostic value of lipoprotein (Lp) (a) in patients who have suffered from coronary artery disease (CAD) has not been fully studied, and the results are inconsistent. This study was conducted to evaluate whether increased Lp(a) concentrations cause differences in clinical adverse outcomes in patients with psoriasis who have already suffered from CAD.

Methods: This retrospective cohort study included consecutive patients with psoriasis and CAD between January 2017 and May 2022 in our hospital.

The efficacy of intraoperatie continuous glucose monitoring in patients undergoing liver transplantation: a study protocol for a prospective randomized controlled superiority trial.

Background: The high incidence of intraoperative glucose dysregulations in liver transplantation (LT) is related to the lack of highly orchestrated control of intraoperative blood glucose. Glucose monitoring based on a single arterial blood gas test can only provide a simple glucose profile and is insufficient in monitoring intraoperative glycemic variability (GV), which is not conducive to controlling GV and may have a lag in the management of hyper/hypoglycemia. Continuous glucose monitor (CGM), which has been successfully applied in the management of chronic disease in diabetes, provides more detailed blood glucose records and reflect GV parameters such as coefficient of variation (CV%).

Development and structure-activity relationships of tanshinones as selective 11β-hydroxysteroid dehydrogenase 1 inhibitors.

11β-Hydroxysteroid dehydrogenase 1 (11β-HSD1) represents a promising drug target for metabolic syndrome, including obesity and type 2 diabetes. Our initial screen of a collection of natural products from Danshen led to the identification of tanshinones as the potent and selective 11β-HSD1 inhibitors. To improve the druggability and explore the structure-activity relationships (SARs), more than 40 derivatives have been designed and synthesized using tanshinone IIA and cryptotanshinone as the starting materials.

Rhynchines A-E: Ca3.1 Calcium Channel Blockers from .

Rhynchines A-E (-), five new indole alkaloids with an unprecedented skeleton, were isolated from . The new skeleton was characterized by an indole moiety and a 2-oxa-8-azatricyclo[6,5,0,0]tridecane core, forming a unique 6/5/7/5/5 ring system. Their structures were determined by nuclear magnetic resonance, high-resolution electrospray ionization mass spectrometry, infrared spectroscopy, and calculated electronic circular dichroism (ECD) and were confirmed by X-ray crystallography.

Discovery of FIXa inhibitors by combination of pharmacophore modeling, molecular docking, and 3D-QSAR modeling.

Human Coagulation Factor IXa (FIXa), specifically inhibited at the initiation stage of the blood coagulation cascade, is an excellent target for developing selective and safe anticoagulants. To explore this inhibitory mechanism, 86 FIXa inhibitors were selected to generate pharmacophore models and subsequently SAR models. Both best pharmacophore model and ROC curve were built through the Receptor-Ligand Pharmacophore Generation module.

Structure-Activity Relationship of Xanthones as Inhibitors of Xanthine Oxidase.

Polygala plants contain a large number of xanthones with good physiological activities. In our previous work, 18 xanthones were isolated from Extented study of the chemical composition of the other species led to the separation of two new xanthones-3-hydroxy-1,2,6,7,8-pentamethoxy xanthone () and 6--β-d-glucopyranosyl-1,7-dimethoxy xanthone ()-together with 14 known xanthones. Among them, some xanthones have a certain xanthine oxidase (XO) inhibitory activity.

Design, Synthesis, and Biological Activities of Vibsanin B Derivatives: A New Class of HSP90 C-Terminal Inhibitors.

Previously, vibsanin B (ViB) was found to preferentially target HSP90β compared to HSP90α. In this study, multiple experiments, including pull-down assays of biotin-ViB with recombinant HSP90β-NTD, MD, CTD, and full-length HSP90β, molecular docking of ViB and its derivatives to the HSP90 CTD, and a inhibition assay of interaction of the HSP90β CTD with GST-tagged cyclophilin 40 (Cyp40) by ViB derivatives, suggest that ViB can directly bind to the HSP90 C-terminus. On the basis of the docking predictions and primary structure-activity relationships (SARs), a series of ViB analogues devised with focus on the C18 position, along with compounds derivatized at the C4, C7, and C8 positions, were designed and chemically synthesized.

Hydrogen bonding-promoted efficient Ru-catalyzed ring-closing metathesis of demanding homoallyl 2-(hydroxymethyl)acrylates.

An efficient hydrogen bonding-guided ring-closing metathesis (RCM) reaction of sterically demanding homoallyl 2-(hydroxymethyl)acrylates catalyzed by the Hoveyda-Grubbs 2nd generation catalyst was developed and the reaction mechanism was explored. Adding a substituent to the hydroxymethyl group in this scaffold resulted in a class of challenging RCM substrates, although usable yields could be obtained. However, substrates bearing a 1-oxygenated alkyl group on the homoallylic carbon gave excellent RCM yields, providing a practical solution.

Melokhanines A-J, Bioactive Monoterpenoid Indole Alkaloids with Diverse Skeletons from Melodinus khasianus.

The new melokhanines A-J (1-10) and 22 known (11-32) alkaloids were isolated from the twigs and leaves of Melodinus khasianus. The new compounds and their absolute configurations were elucidated by extensive analysis of spectroscopic, X-ray diffraction, and computational data. Melokhanine A (1), composed of a hydroxyindolinone linked to an octahydrofuro[2,3-b]pyridine moiety, is an unprecedented monoterpenoid indole alkaloid.

Three Minor Diterpenoids with Three Carbon Skeletons from Euphorbia peplus.

Euphorbia peplus has been used in traditional medicine to treat asthma and psoriasis. Three highly modified diterpenoids, namely, pepluacetal (1) and pepluanol A-B (2-3), have been isolated and identified from this plant. Compounds 1-3 exhibit unprecedented 5/4/7/3, 5/6/7/3, and 5/5/8/3 ring systems, respectively.

Epigenetic regulation of NKG2D ligands is involved in exacerbated atherosclerosis development in Sirt6 heterozygous mice.

Sirt6 is a member of the class III histone deacetylase family which is associated with aging and longevity. Sirt6 deficient mice show an aging-like phenotype, while male transgenic mice of Sirt6 show increased longevity. Sirt6 acts as a tumor suppressor and deficiency of Sirt6 leads to cardiac hypertrophy and heart failure.

Hepatic Oncostatin M Receptor β Regulates Obesity-Induced Steatosis and Insulin Resistance.

The liver is an essential insulin-responsive organ that is critical for maintaining glucose homeostasis and lipid metabolism. Oncostatin M receptor β chain (OSMRβ) is implicated in adipose tissue- and immune cell-mediated metabolic regulation. However, the role of hepatocyte-derived OSMRβ in metabolic disorders remains unclear.

Lingzhilactones from Ganoderma lingzhi ameliorate adriamycin-induced nephropathy in mice.

Ethnopharmacological Relevance: Several Ganoderma fungi are well-known for their medical uses to treat cancer, insomnia and kidney disease in East Asia. Triperpenoids and polysaccharides have been considered for a long time to be the major active components of the genus Ganoderma. The present study is to examine the effects of lingzhilactones from G.

Periplanosides A-C: new insect-derived dihydroisocoumarin glucosides from Periplaneta americana stimulating collagen production in human dermal fibroblasts.

Three new dihydroisocoumarin glucosides, termed periplanosides A-C (1-3), a known analog, pericanaside (4), and the other twenty known compounds were isolated from the insect Periplaneta americana. Their structures including absolute configurations were determined by comprehensive spectroscopic analyses and computational methods. Biological evaluation showed that compound 2 could stimulate collagen production by 31.

Oncostatin M Confers Neuroprotection against Ischemic Stroke.

Unlabelled: Cell-surface receptors provide potential targets for the translation of bench-side findings into therapeutic strategies; however, this approach for the treatment of stroke is disappointing, at least partially due to an incomplete understanding of the targeted factors. Previous studies of oncostatin M (OSM), a member of the gp130 cytokine family, have been limited, as mouse models alone may not strongly resemble the human condition enough. In addition, the precise function of OSM in the CNS remains unclear.

Neuron-Specific Tumor Necrosis Factor Receptor-Associated Factor 3 Is a Central Regulator of Neuronal Death in Acute Ischemic Stroke.

Neuronal death after ischemic stroke involves multiple pathophysiological events, as well as a complex molecular mechanism. Inhibiting a single therapeutic target that is involved in several ischemic signaling cascades may be a promising strategy for stroke management. Here, we report the versatile biological roles of tumor necrosis factor receptor-associated factor 3 (TRAF3) in ischemic stroke.

Structure-Based Optimization and Biological Evaluation of Pancreatic Lipase Inhibitors as Novel Potential Antiobesity Agents.

The unusual fused β-lactone vibralactone was isolated from cultures of the basidiomycete Boreostereum vibrans and has been shown to significantly inhibit pancreatic lipase. In this study, a structure-based lead optimization of vibralactone resulted in three series of 104 analogs, among which compound C1 exhibited the most potent inhibition of pancreatic lipase, with an IC50 value of 14 nM. This activity is more than 3000-fold higher than that of vibralactone.

Two New Classes of T-Type Calcium Channel Inhibitors with New Chemical Scaffolds from Ganoderma cochlear.

T-type calcium channel (TTCC) inhibitors hold great potential for the treatment of a variety of neurological disorders. Cochlearoids A-E (1-5), five pairs of dimeric meroterpenoid enantiomers, and cochlearines A (6) and B (7), two pairs of enantiomeric hybrid metabolites, were isolated and characterized from Ganoderma cochlear. Biological evaluation found that compounds (+)-1, (-)-3, and (±)-6 significantly inhibited Cav3.

Metabolites from the mushroom Ganoderma lingzhi as stimulators of neural stem cell proliferation.

Ganoderma lingzhi is a valuable, edible and medicinal fungus that has been widely used for the prevention and treatment of a broad range of diseases. In this study, spirolingzhines A-D, four meroterpenoids with a spiro[benzofuran-2,10-cyclopentane] motif, lingzhines A-F, six meroterpenoids with diverse ring systems, along with two known compounds were isolated from the fruiting bodies of this fungus. The structures and stereochemistry of these substances were determined by using spectroscopic, X-ray crystallographic and computational methods.

Bioactive compounds from the insect Aspongopus chinensis.

Recent studies focusing on unveiling the biological agents of Aspongopus chinensis have led to the identification of four new norepinephrine derivatives (1-4), three new sesquiterpenoids (5-7), and one new lactam (8). In addition, twenty-three known compounds have been identified, most of which were isolated from this insect for the first time. Selected members of insect-derived substances were evaluated for their biological activities against renal protection in high-glucose-induced mesangial cells and COX-2 inhibition.

Identification and validation of p50 as the cellular target of eriocalyxin B.

As an ent-kaurene diterpenoid isolated from Isodon eriocalyx var. Laxiflora, Eriocalyxin B (EriB) possesses potent bioactivity of antitumor and anti-autoimmune inflammation, which has been suggested to work through inhibition of NF-kappaB (NF-κB) signaling. However, the direct target of EriB remains elusive.

Compounds from the Chinese black ant (Polyrhachis dives) and NMR behavior of the isomers with formamide group.

Two new dopamine derivatives divesamides A (1) and B (2), along with six known N-containing compounds were isolated from the Chinese black ant (Polyrhachis dives). Their structures were determined on the basis of spectroscopic methods. Compound 1 is a racemate, and chiral HPLC separation yielded a pair of antipodes.

Cytotoxic bibenzyl dimers from the stems of Dendrobium fimbriatum Hook.

The bioassay-guided chemical investigation of the stems of Dendrobium fimbriatum Hook led to the isolation of seven first reported bibenzyl dimers with a linkage of a methylene moiety, fimbriadimerbibenzyls A-G (1-7), together with a new dihydrophenanthrene derivative (S)-2,4,5,9-tetrahydroxy-9,10-dihydrophenanthrene (8) and thirteen known compounds (9-21). The structure of the new compound was established by spectroscopic analysis. Biological evaluation of bibenzyl derivatives against five human cell lines indicated that seven of those compounds exhibited broad-spectrum and cytotoxic activities with IC50 values ranging from 2.