Verruculosins A-B, New Oligophenalenone Dimers from the Soft Coral-Derived Fungus .

In an effort to discover new bioactive anti-tumor lead compounds, a specific tyrosine phosphatase CDC25B and an Erb family receptor EGFR were selected as drug screening targets. This work led to the investigation of the soft coral-derived fungus and identification of two new oligophenalenone dimers, verruculosins A-B (-), along with three known analogues, bacillisporin F (), duclauxin (), and xenoclauxin (). Compound was the first structure of the oligophenalenone dimer possessing a unique octacyclic skeleton.

A New Use for an Old Drug: Carmofur Attenuates Lipopolysaccharide (LPS)-Induced Acute Lung Injury Inhibition of FAAH and NAAA Activities.

Acute lung injury (ALI), characterized by a severe inflammatory process, is a complex syndrome that can lead to multisystem organ failure. Fatty acid amide hydrolase (FAAH) and -acylethanolamine acid amidase (NAAA) are two potential therapeutic targets for inflammation-related diseases. Herein, we identified carmofur, a 5-fluorouracil-releasing drug and clinically used as a chemotherapeutic agent, as a dual FAAH and NAAA inhibitor.

Design, synthesis and biological evaluation of AT receptor blockers derived from 6-substituted aminocarbonyl benzimidazoles.

A series of new 6-substituted aminocarbonyl benzimidazole derivatives with 1, 4-disubsituted or 1, 5-disubsituted indole moiety and benzoic acid moiety were designed, synthesized and pharmacologically evaluated. Most of the synthesized compounds could bind to the AT receptor and decrease blood pressure significantly. Notably, 2e and 1h could obviously decrease MBP in a dose dependent manner.

Effect and mechanism of verbascoside on hypoxic memory injury in plateau.

Verbascoside is a water-soluble natural phenylethanoid glycoside and distributes widely in plants. It has been proved with antioxidant, neuroprotective, anti-inflammatory, antibacterial, and immunomodulatory bioactivities. In this experiment, the effect and mechanism of verbascoside on hypoxic memory injury were studied in a low-pressure and low-oxygen chamber.

A multiple breast cancer stem cell model to predict recurrence of T, N breast cancer.

Background: Local or distant relapse is the key event for the overall survival of early-stage breast cancer after initial surgery. A small subset of breast cancer cells, which share similar properties with normal stem cells, has been proven to resist to clinical therapy contributing to recurrence.

Methods: In this study, we aimed to develop a prognostic model to predict recurrence based on the prevalence of breast cancer stem cells (BCSCs) in breast cancer.

Gene Is Associated With Clinical Response to SNRIs in a Local Chinese Han Population.

The relation between the () gene and major depressive disorder (MDD) has been studied in a local Chinese Han population. MDD is associated with the rs2032582 () and rs1128503 () single-nucleotide polymorphisms (SNPs) of but not with rs1045642, rs2032583, rs2235040, and rs2235015. This study aims to explore the potential correlations of therapeutic responses with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) in a local Chinese Han population.

Identification of a rhodanine derivative BML-260 as a potent stimulator of UCP1 expression.

Identification of proper agents to increase or activate UCP1 cells in adipose tissues remains a potent therapeutic strategy to combat obesity. Screening systems for UCP1 activators have been previously established and allow for unbiased discovery of effective compound(s). A previously established -2A-GFP reporter system was applied to a chemical library containing 33 phosphatase inhibitors.

N-glycosylation of uterine endometrium determines its receptivity.

Glycosylation alters the molecular and functional features of glycoproteins, which is closely related with many physiological processes and diseases. During "window of implantation", uterine endometrium transforms into a receptive status to accept the embryo, thereby establishing successful embryo implantation. In this article, we aimed at investigating the role of N-glycosylation, a major modification type of glycoproteins, in the process of endometrial receptivity establishment.

Progesterone promotes embryo adhesion by upregulating c-Fos/c-Jun transcription factor-mediated poFUT1 expression†.

The proliferation and adhesion abilities of placental trophoblasts are critical for embryo implantation and successful pregnancy. Protein O-fucosyltransferase 1 (poFUT1) and the transcription factor c-Fos/c-Jun have been found to promote trophoblastic cell invade into the endometrium. Progesterone is critical to the regulation of embryonic implantation.

Pyrroloindoline cyclization in tryptophan-containing cyclodipeptides mediated by an unprecedented indole C3 methyltransferase from Streptomyces sp. HPH0547.

Diverse bioactive alkaloids with a tryptophan 2,5-diketopiperazine (DKP) core and an annulated structure forming a methylated pyrroloindoline-DKP assembly have been isolated from various microbial sources. However, little is known about their biosynthesis. In this study, a novel indole C3 methyltransferase from Streptomyces sp.

Cardioprotective mechanisms of salvianic acid A sodium in rats with myocardial infarction based on proteome and transcriptome analysis.

Ischemic heart diseases (IHDs) cause great morbidity and mortality worldwide, necessitating effective treatment. Salvianic acid A sodium (SAAS) is an active compound derived from the well-known herbal medicine Danshen, which has been widely used for clinical treatment of cardiovascular diseases in China. This study aimed to confirm the cardioprotective effects of SAAS in rats with myocardial infarction and to investigate the underlying molecular mechanisms based on proteome and transcriptome profiling of myocardial tissue.

Synthesis and antitumor activity of three novel ginsenoside M1 derivatives with 3'-ester modifications.

Ginsenoside M1 (M1) was considered to be the main antitumor component of ginsenoside metabolites in the body. In order to enhance its potency on antitumor effect, three novel M1 3'-ester derivatives (1c, 2c, 3c) were synthesized and evaluated. The yield of these derivatives was between 41% and 69%.

poFUT1 promotes endometrial decidualization by enhancing the O-fucosylation of Notch1.

Background: Endometrial stromal cell decidualization is critical for embryo implantation. Dysfunctional decidualization leads to implantation failure, miscarriage and even pregnancy associated disorders in subsequent pregnancy trimesters. Protein glycosylation is involved in many physiological and pathological processes.

Downregulation of HDAC3 by ginsenoside Rg3 inhibits epithelial-mesenchymal transition of cutaneous squamous cell carcinoma through c-Jun acetylation.

The metastatic rate of human cutaneous squamous cell carcinoma (CSCC) has increased in recent years. Despite the current advances in therapies, effective treatments remain lacking. Ginsenoside 20(R)-Rg3 is an effective antitumor monomer extracted from ginseng, but the role of Rg3 in CSCC remains unknown.

A Subtle Network Mediating Axon Guidance: Intrinsic Dynamic Structure of Growth Cone, Attractive and Repulsive Molecular Cues, and the Intermediate Role of Signaling Pathways.

A fundamental feature of both early nervous system development and axon regeneration is the guidance of axonal projections to their targets in order to assemble neural circuits that control behavior. In the navigation process where the nerves grow toward their targets, the growth cones, which locate at the tips of axons, sense the environment surrounding them, including varies of attractive or repulsive molecular cues, then make directional decisions to adjust their navigation journey. The turning ability of a growth cone largely depends on its highly dynamic skeleton, where actin filaments and microtubules play a very important role in its motility.

N-Acylethanolamine acid amidase (NAAA) inhibitor F215 as a novel therapeutic agent for osteoarthritis.

Osteoarthritis (OA), characterized by cartilage damage, synovitis inflammation and chronic pain, is a common degenerative joint disease that may lead to physical disability. In the present study, we first explored the association between N-Acylethanolamine acid amidase (NAAA) and OA progression, and then examined the capability of the NAAA inhibitor F215 to attenuate osteoarthritis. Increased NAAA expressions and decreased PEA levels in synovial membrane and lumbar spinal cord were observed in MIA induced osteoarthritic rats.

Online health information in a rural residential population in Zhejiang Province, China: a cross-sectional study.

Objective: To determine the prevalence, degree of trust and usefulness of the online health information seeking source and identify associated factors in the adult population from the rural region of China.

Design: A cross-sectional population-based study.

Setting: A self-designed questionnaire study was conducted between May and June 2015 in four districts of Zhejiang Province.

Catalpol improves axonal outgrowth and reinnervation of injured sciatic nerve by activating Akt/mTOR pathway and regulating BDNF and PTEN expression.

: This study aimed to investigate the effects of catalpol on sciatic nerve crush injury (SNCI) and further explore the role of Akt/mTOR pathway in its pharmacological efficacy. : Mice with SNCI in the right were treated with catalpol. Rapamycin was used to block mTOR signal activation.

Central and Peripheral Changes in FOS Expression in Schizophrenia Based on Genome-Wide Gene Expression.

Schizophrenia is a chronic, debilitating neuropsychiatric disorder. Multiple transcriptomic gene expression profiling analysis has been used to identify schizophrenia-associated genes, unravel disease-associated biomarkers, and predict clinical outcomes. We aimed to identify gene expression regulation, underlying pathways, and their roles in schizophrenia pathogenesis.

Synthesis, biological evaluation, and structure activity relationship (SAR) study of pyrrolidine amide derivatives as -acylethanolamine acid amidase (NAAA) inhibitors.

-Acylethanolamine acid amidase (NAAA) is one of the key enzymes involved in the degradation of fatty acid ethanolamides (FAEs), especially for palmitoylethanolamide (PEA). Pharmacological blockage of NAAA restores PEA levels, providing therapeutic benefits in the management of inflammation and pain. In the current work, we showed the structure-activity relationship (SAR) studies for pyrrolidine amide derivatives as NAAA inhibitors.

[Value of three-dimensional visualization technology in preoperative evaluation of liver autotransplantation for end-stage hepatic alveolar echinococcosis].

Objective: To evaluate the value of the three-dimensional visualization technology for the preoperative assessment of liver autotransplantation for end-stage hepatic alveolar echinococcosis.

Methods: A total of 8 patients with end-stage hepatic alveolar echinococcosis undergoing liver autotransplantation in Qinghai Provincial People's Hospital from May 2013 to July 2017 were collected. All cases received preoperative abdominal CT scanning and dynamic three-phase enhanced CT scanning, and the original CT data were transferred to the human 3D visualization virtual surgical planning system.

[Expression of follicular helper T cells in peripheral blood of patients with hepatic echinococcosis].

Objective: To detect the expression of follicuLar helper T cells (Tfh) and interleukin-21 (IL-21) in the peripheral blood of patients with hepatic echinococcosis and healthy controls, so as to explore the associations of Tfh and IL-21 expression with the progression of hepatic echinococcosis.

Methods: Fifty cases of hepatic echinococcosis and healthy controls were collected from Qinghai Provincial People's Hospital, respectively. Flow cytometry was used to detect the expression of Tfh cells in the peripheral blood of hepatic echinococcosis patients and healthy controls, and enzyme-linked immunosorbent assay (ELISA) was used to detect serum IL-21 expression in hepatic echinococcosis patients and healthy controls.

VEGF attenuates lung injury by inducing homing of CD133 progenitors via VEGFR1.

Although vascular endothelial growth factor (VEGF) promotes vascular permeability and results in edema, studies have suggested it may protect the lung from inflammatory injury via poorly understood mechanisms. Using a mouse model of extracorporeal circulation (ECC), we found that levels of intravenous VEGF increased in lung tissue and inhibited inflammation, thereby attenuating lung injury. These effects could be obtained by intravenous injection or inhalation of VEGF, and they were abolished by treatment with anti-VEGF antibody.