Photoredox-Catalyzed C-H Methylation of -Heteroarenes Enabled by ,-Dimethylethanolamine.

A visible-light-driven radical C-H methylation of -heteroarenes that is efficient and additive- and catalyst-free and employs readily available ,-dimethylethanolamine as the methyl source has been developed. The transformation offers the benefits of broad substrate scope, mild reaction conditions, and operational simplicity. A photoactive electron donor-acceptor (EDA) complex between -heteroarenes and ,-dimethylethanolamine is essential for this transformation, as revealed by mechanistic investigations.

Probing the interactions of genistein with HMGB1 through multi-spectroscopic and in-silico approaches.

Functional regulation of proteins by ligand-protein interactions plays a crucial role in understanding biological processes and identifying potential drugs. High mobility group box 1 (HMGB1) plays a pivotal role in sterile inflammation as a key immunomodulatory protein. Genistein, a well-known isoflavone compound, has been shown to have neuroprotective effects.

A retrospective study on the influence of inclination of cusp on implant marginal bone height in patients with periodontal disease.

To investigate the correlation between the marginal bone height of implants in the posterior maxilla of patients with periodontal disease and the inclination of cusp, providing a theoretical basis for the occlusal design of implant restorations in such patients.  Methods: A total of 80 patients with periodontal disease who underwent implant restoration in the posterior maxilla (55 men and 25 women; mean age 56.66 ± 12.

Isolation and microbial transformation of tea sapogenin from seed pomace of Camellia oleifera with anti-inflammatory effects.

In the current study, tea saponin, identified as the primary bioactive constituent in seed pomace of Camellia oleifera Abel., was meticulously extracted and hydrolyzed to yield five known sapogenins: 16-O-tiglogycamelliagnin B (a), camelliagnin A (b), 16-O-angeloybarringtogenol C (c), theasapogenol E (d), theasapogenol F (e). Subsequent biotransformation of compound a facilitated the isolation of six novel metabolites (a1-a6).

Discovery of Potent and Selective CB2 Agonists Utilizing a Function-Based Computational Screening Protocol.

Nowadays, the identification of agonists and antagonists represents a great challenge in computer-aided drug design. In this work, we developed a computational protocol enabling us to design/screen novel chemicals that are likely to serve as selective CB2 agonists. The principle of this protocol is that by calculating the ligand-residue interaction profile (LRIP) of a ligand binding to a specific target, the agonist-antagonist function of a compound is then able to be determined after statistical analysis and free energy calculations.

Visible-Light-Induced Regioselective Radical Oxo-Amination of Alkenes with O as the Oxygen Source.

An efficient and novel visible-light-induced oxo-amination of terminal alkenes for the construction of α-amino ketones with easily accessible and green O as the oxygen source has been developed. The transformation possesses the advantages of operational simplicity, a broad substrate scope, high atom economy, and mild reaction conditions. The mechanistic studies reveal that an energy transfer process probably occurs in the initial stage, and the reaction proceeds via β-scission of the alkoxyl radical species.

The combined effect of a novel formula of herbal extracts on bacterial infection and immune response in .

Herbal extracts have been considered as ideal alternative to antibiotics in aquaculture and application of combinatory effective extracts always can exhibit the enhanced bioactivity with high efficiency. In our study, a novel herbal extract combination GF-7, which is composed of , extracts as well as the effective parts of and Georgi extracts, was prepared and applied for the therapy of bacterial infection in aquaculture. The HPLC analysis of GF-7 was also investigated for quality control and chemical identification.

Microbial-Catalyzed Baeyer-Villiger Oxidation for 3,4--Triterpenoids as Potential HMGB1 Inhibitors.

Pentacyclic triterpenoids are considered to be the potential HMGB1 inhibitors, but due to the limited number of hydrogen bond donors and the number of rotatable bonds in the rigid skeletons, their further chemical biology research with this target was restricted. To improve these profiles, microbial-catalyzed Baeyer-Villiger oxidation of the primary ursane and oleanane-type triterpenoids including uvaol (), erythrodiol (), oleanolic acid (), and ursolic acid () was performed by CICC 23628. As a result, ten new and one known A-ring cleaved metabolites were obtained and the possible biogenetic pathways were also discussed based on the HPLC-MS analysis.

Targeting dual-specificity tyrosine phosphorylation-regulated kinase 2 with a highly selective inhibitor for the treatment of prostate cancer.

Prostate cancer (PCa) is one of the most prevalent cancers in men worldwide, and hormonal therapy plays a key role in the treatment of PCa. However, the drug resistance of hormonal therapy makes it urgent and necessary to identify novel targets for PCa treatment. Herein, dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) is found and confirmed to be highly expressed in the PCa tissues and cells, and knock-down of DYRK2 remarkably reduces PCa burden in vitro and in vivo.

Microbial transformation and inhibitory effect assessment of uvaol derivates against LPS and HMGB1 induced NO production in RAW264.7 macrophages.

For the discovery of new pentacyclic triterpenes as a potential anti-inflammatory agent, microbial transformation of uvaol by Penicilium griseofulvum CICC 40293 and Streptomyces griseus ATCC 13273 was investigated. Stereoselective hydroxylation and epoxidation reactions were observed in the biotransformation. Moreover, six new metabolites were isolated and structurally elucidated by HR-ESI-MS and NMR spectrum.

Synthesis and biological evaluation of celastrol derivatives as potent antitumor agents with STAT3 inhibition.

Using STAT3 inhibitors as a potential strategy in cancer therapy have attracted much attention. Recently, celastrol has been reported that it could directly bind to and suppress the activity of STAT3 in the cardiac dysfunction model. To explore more effective STAT3 inhibiting anti-tumour drug candidates, we synthesised a series of celastrol derivatives and biologically evaluated them with several human cancer cell lines.

Microbial transformation of pentacyclic triterpenes for anti-inflammatory agents on the HMGB1 stimulated RAW 264.7 cells by Streptomyces olivaceus CICC 23628.

High mobility group box-1 protein (HMGB1) is a typical Damage-Associated Molecular Patterns (DAMPs) released in response to cellular inflammation. The pentacyclic triterpenes (PTs) are considered to be the natural inhibitors against HMGB1-related inflammation. To explore new lead compounds of PTs as anti-inflammatory agents, biotransformation of four PTs by Streptomyces olivaceus CICC 23628 was investigated in this study.

Design, synthesis, and biological evaluation of novel tetrahydroprotoberberine derivatives to reduce SREBPs expression for the treatment of hyperlipidemia.

Statins play an important role in the treatment of hyperlipidemia, but drug resistance and adverse effects greatly limits their application. To discover new lipid-lowering drugs, three different series of tetrahydroprotoberberine derivatives (THPBs) were designed and synthesized. These compounds were first tested for their effects on viability of HepG2 cells and 21 compounds with the percent of cell viability over 90% were further screened to evaluate their ability to reduce total cholesterol (TC) and triglyceride (TG) levels.

Design, Synthesis and Biological Evaluation of Steroidal Glycoconjugates as Potential Antiproliferative Agents.

To systematically evaluate the impact of neoglycosylation upon the anticancer activities and selectivity of steroids, four series of neoglycosides of diosgenin, pregnenolone, dehydroepiandrosterone and estrone were designed and synthesized according to the neoglycosylation approach. The structures of all the products were elucidated by NMR analysis, and the stereochemistry of C20-MeON-pregnenolone was confirmed by crystal X-ray diffraction. The compounds' cytotoxicity on five human cancer cell lines was evaluated using a Cell Counting Kit-8 assay, and structure-activity relationships (SAR) are discussed.

Two novel compound heterozygous mutations in NGLY1as a cause of congenital disorder of deglycosylation: a case presentation.

Background: NGLY1-related congenital disorder of deglycosylation (NGLY1-CDDG) is a multisystemic neurodevelopmental disorder in which affected individuals show developmental delay, epilepsy, intellectual disability, abnormal liver function, and poor growth. This study presents a 10-month-old female infant with elevated liver transaminases, developmental delay, epilepsy (subclinical seizures), and constipation who possesses two compound heterozygous mutations in NGLY1.

Case Presentation: The proband was admitted to the Department of Gastroenterology, Children's Hospital of Soochow University, with elevated liver transaminases.

Biocatalytic allylic hydroxylation of unsaturated triterpenes and steroids by Bacillus megaterium CGMCC 1.1741.

In this study, we described the microbial catalyzed allylic oxidation by Bacillus megaterium CGMCC 1.1741 of three Δ-pentacyclic triterpenes, erythrodiol (1), uvaol (2), hederagenin (3) and of four steroids including Δ-steroids, diosgenin (4), pennogenin (5), 25(R,S)-ruscogenin (6) and Δ-steroid, diosgenone (7). As a result, fourteen metabolites were generated with allyl hydroxyl moiety.

Trifluoperazine as an alternative strategy for the inhibition of tumor growth of colorectal cancer.

The development of cancer in patients with schizophrenia is affected by genetic and environmental factors and antipsychotic medication. Several studies found that schizophrenia was associated with decreased risk of some cancers, and the neuroleptic medication might help to reduce the risk of colorectal cancer (CRC). Phenothiazine drugs including trifluoperazine (TFP) are widely used antipsychotic drugs and showed some antitumor effects, we here investigated the potential application of TFP in the treatment of colon cancer.

Chemical synthesis, microbial transformation and biological evaluation of tetrahydroprotoberberines as dopamine D1/D2 receptor ligands.

Dopamine D1/D2 receptors are important targets for drug discovery in the treatment of central nervous system diseases. To discover new and potential D1/D2 ligands, 17 derivatives of tetrahydroprotoberberine (THPB) with various substituents were prepared by chemical synthesis or microbial transformation using Streptomyces griseus ATCC 13273. Their functional activities on D1 and D2 receptors were determined by cAMP assay and calcium flux assay.

Significantly different effects of tetrahydroberberrubine enantiomers on dopamine D1/D2 receptors revealed by experimental study and integrated in silico simulation.

Tetrahydroberberrubine (TU), an active tetrahydroprotoberberines (THPBs), is gaining increasing popularity as a potential candidate for treatment of anxiety and depression. One of its two enantiomers, l-TU, has been reported to be an antagonist of both D1 and D2 receptors, but the functional activity of the other enantiomer, d-TU, is still unknown. In this study, experiments were combined with in silico molecular simulations to (1) confirm and discover the functional activities of l-TU and d-TU, and (2) systematically evaluate the molecular mechanisms beyond the experimental observations.

Design and activity study of a melittin-thanatin hybrid peptide.

The unique antimicrobial mechanism of antimicrobials make them a promising substitute for antibiotics for fighting drug-resistant bacteria. Both melittin and thanatin have antimicrobial bioactivity. However, thanatin does not inhibit the growth of Staphylococcus aureus.

A meta-analysis of dietary carbohydrate intake and inflammatory bowel disease risk: evidence from 15 epidemiology studies.

Background And Purpose: epidemiological studies that assess the association of dietary total carbohydrate intake and inflammatory bowel disease risk (IBD) have yielded controversial results. Therefore, this study of various epidemiological studies was conducted in order to explore this relationship.

Methods: a systematic literature search of the PubMed, Embase, Web of Science and Medline databases was performed up to September 2017.

Effect of Montmorillonite on 4-Nonylphenol Enrichment in Zebrafish.

The aim of this study was to investigate the effect of montmorillonite on nonylphenol (4-nonylphenol, 4-NP) enrichment in a zebrafish model. The AB strain zebrafish were used as the animal subjects, and three concentration gradients were set for both nonylphenol and montmorillonite, according to their actual concentrations in aquaculture water in Huzhou City. A group treated with nonylphenol alone was also set, adding up to 12 experimental groups.

Sodium Phenylbutyrate Inhibits Tumor Growth and the Epithelial-Mesenchymal Transition of Oral Squamous Cell Carcinoma In Vitro and In Vivo.

Sodium phenylbutyrate (SPB) as a salt of 4-phenylbutyric acid (4-PBA) has been reported to be an ammonia scavenger, histone deacetylase inhibitor, and an endoplasmic reticulum stress inhibitor in various diseases, including neurological diseases, inflammatory disorders, and carcinogenesis. Although phenylbutyrate showed effective antitumor properties in many cancers, its role in oral squamous cell carcinoma (OSCC) remains further characterized. Thus, the OSCC cell lines CAL27, HSC3, and SCC4 were treated with a series of doses of SPB for different times.

Diversity synthesis of tetrahydroprotoberberines glycosides by combined chemical and microbial catalysis.

The present study was designed to construct the structurally diverse library of tetrahydroprotoberberines (THPBs) by combining the methods of chemical nonselective demethylation and microbial glycosylation. HPLC-MS/MS analyses tentatively identified 12 de-methylated and 9 glycosylated derivates of THPBs and 5 rarely oxidized glycosides of THPBs in the library. Through this effort, we achieved not only a variety of the THPBs and their glycosides but also tested the catalytic characteristics and capabilities of G.