Clinical Significance of Serum-Derived Exosomal LINC00917 in Patients With Non-Small Cell Lung Cancer.

Background: In this study, we aimed to explore the diagnostic potential of serum-based exosomal long intergenic noncoding RNA 917 (LINC00917) in non-small cell lung cancer (NSCLC). Methods: Exosomes were extracted from NSCLC patients' serum samples. Exosomal LINC00917 expression levels were compared, by qRT-PCR, between cancer patients and healthy controls, as well as sub-populations of cancer patients. The association between exosomal LINC00917 expression and NSCLC patients' clinicopathologic factors were investigated, and receiver operating characteristic (ROC) curves were drawn. In addition, NSCLC patients' overall survivals (OSs) was examined based on exosomal LINC00917 expression and further evaluated by the cox regression analysis. Results: Serum-derived exosomal LINC00917 was highly expressed in NSCLC patients, and further upregulated in stage III/IV cancer patients. Exosomal LINC00917 yielded modestly good under the curve (AUC) values. Upregulated exosomal LINC00917 expression was closely associated with cancer patients' advanced stages and shorter OSs. Conclusion: Serum-derived exosomal LINC00917 may hold diagnostic potential for patients with non-small cell lung cancer.

Defect-engineered transition metal hydroxide nanosheets realizing tumor-microenvironment-responsive multimodal-imaging-guided NIR-II photothermal therapy.

Exploiting two-dimensional nanomaterials as photo-based theranostic agents is promising for the highly efficient ablation of deep-tissue-buried tumors. However, they are limited by their poor absorption in the second near-infrared-light (NIR-II) bio-window (1000-1300 nm) and intrinsic nonbiodegradability. Herein, defect-rich sulfur-doped Ni(OH)2 (S-Ni(OH)2) nanosheets decorated with bovine serum albumin (BSA) as a novel theranostic agent is developed, which can accomplish multimodal-imaging-guided photothermal ablation of mouse cancers in the NIR-II bio-window. Sulfur doping extends the absorption spectra of Ni(OH)2 nanosheets from the visible to NIR-II bio-window, affording highly efficient photothermal conversion (58.20% for 1064 nm), entailing it to become an excellent contrast agent for photoacoustic imaging. Further, because of their intrinsic paramagnetic property, they can be applied for magnetic resonance imaging. Owing to the abundant defective sites in S-Ni(OH)2 nanosheets, they exhibit response to the tumor microenvironment, resulting in effective biodegradation and excretion from the body. In vivo toxicity experiments indicated that S-Ni(OH)2-BSA NSs delivered no appreciable toxicity and good biocompatibility. This work provides an avenue for the rational design of effective theranostics agents.

Iridoid glycosides and glycosidic constituents from Eriophyton wallichii Benth.

C9-iridoid glycosides, wallichiisides A-C, and four dimers, wallichiisides D-G, together with 13 known glycosidic compounds, were isolated from whole plants of Eriophyton wallichii Benth. Their structures were elucidated by spectroscopic methods and comparison with literature values. Four of these compounds showed moderate DPPH free radical scavenging activity.

[Effects of phytoestrogens on testosterone production of rat Leydig cells].

OBJECTIVE: To investigate the effects of phytoestrogens (daidzein and genistein) on the testosterone production of rat Leydig cells and the possible mechanisms. METHODS: Primary Leydig cells were obtained from 3-month old male SD rats using discontinuous Percoll density gradient centrifugation. The effects of phytoestrogens at various concentrations were evaluated by ELISA, with hCG as the positive control. The mRNA expression of P450 side-chain cleavage enzyme (P450scc) was analyzed by semi-quantitative RT-PCR. RESULTS: Genistein at 0.1 micromol/L obviously promoted the secretion of testosterone and upregulated the mRNA level of P450scc. At a higher concentration of 5 micromol/L, however, both daidzein and genistein significantly inhibited the testosterone production of Leydig cells (P > 0.05). CONCLUSION: Genistein can promote the testosterone production of Leydig cells at a low concentration (0.1 micromol/L), but both daidzein and genistein can inhibit it at a higher concentration ( >5 micromol/L).

Effects of Pro-Arg, a novel dipeptide derived from protamine hydrolysate on H2O2-induced oxidative stress in human diploid fibroblasts.

Oxidative stress plays an important role in tissue damage associated with many different chronic degenerative diseases, such as cancer and cardiovascular disorders. In our previous study, a novel dipeptide Pro-Arg derived from protamine hydrolysates was found to possess significant antioxidative activity in vitro. In this study, we compared the antioxidant capabilities of purified and synthesized dipeptide (Pro-Arg) and found both of them had very strong hydroxyl-radical scavenging activity in vitro, even at a very low concentration. The protective effect of the dipeptide against oxidative stress was evaluated using H2O2-induced oxidative stress of human diploid fibroblasts MRC-5 cell model. Our results showed the dipeptide attenuated H2O2-induced cellular oxidative damage, and normalized S phase arrest of MRC-5 cells exposed to H2O2. Our findings demonstrate that Pro-Arg can protect against oxidative stress/damage and H2O2-induced human diploid fibroblasts cell death.

Bacterial translation inhibitors, 1-acylindazol-3-ols as anthranilic acid mimics.

The discovery and initial optimization of a novel anthranilic acid derived class of antibacterial agents has been described in a recent series of papers. This paper describes the discovery of 1-acylindazol-3-ols as a novel bioisostere of an anthranilic acid. The synthesis and structure-activity relationships of the indazol bioisosteres are described herein.

Discovery and characterization of QPT-1, the progenitor of a new class of bacterial topoisomerase inhibitors.

QPT-1 was discovered in a compound library by high-throughput screening and triage for substances with whole-cell antibacterial activity. This totally synthetic compound is an unusual barbituric acid derivative whose activity resides in the (-)-enantiomer. QPT-1 had activity against a broad spectrum of pathogenic, antibiotic-resistant bacteria, was nontoxic to eukaryotic cells, and showed oral efficacy in a murine infection model, all before any medicinal chemistry optimization. Biochemical and genetic characterization showed that the QPT-1 targets the beta subunit of bacterial type II topoisomerases via a mechanism of inhibition distinct from the mechanisms of fluoroquinolones and novobiocin. Given these attributes, this compound represents a promising new class of antibacterial agents. The success of this reverse genomics effort demonstrates the utility of exploring strategies that are alternatives to target-based screens in antibacterial drug discovery.

[Studies on phenylpropanoids from herbs of Eriophyton wallichii].

OBJECTIVE: To study the chemical constituents of Eriophyton wallichii. METHOD: Compounds were separated and purified by column chromatographic methods, and their structures were elucidated by spectroscopic methods. RESULT: Eight phenylpropanoids were isolated and identified as martynoside (1), leucosceptoside A (2), citrusin B (3), (+)-dehydrodiconiferyl alcohol-4, 9-beta-D-glucopyranoside (4), liriodendrin (5), velutinoside 11[ (6), jionoside B, (7), stachysoside D (8), respectively. CONCLUSION: The eight compounds were firstly isolated from E. wallichii.

Preparation of novel anthranilic acids as antibacterial agents. Extensive evaluation of alternative amide bioisosteres connecting the A- and the B-rings.

In the past few years, a significant effort has been devoted by Pharmacia toward the discovery of novel antibiotics. We have recently described the identification of an anthranilic acid lead 1 and the optimization resulting in the advanced lead 2. In this report, we describe the preparation of several selected amide bioisosteres connecting the A- and the B-rings. The E-alkene provided a rigid analog with equal potency to the corresponding amide. This indicates that the amide is not a recognition element rather acts as an appropriate spatial linker of the two important aryl A and B rings. The work here clearly demonstrates that the amide linker can be replaced with several functionalities without significant deterioration in the MIC activity.

Design, synthesis, structure-activity relationship, and in vivo activity of azabicyclic aryl amides as alpha7 nicotinic acetylcholine receptor agonists.

A novel set of azabicyclic aryl amides have been identified as potent and selective agonists of the alpha7 nAChR. A two-pronged approach was taken to improve the potential hERG liability of previously disclosed alpha7 nAChR agonist, PNU-282,987, while maintaining the compound's other desirable pharmacological properties. The first approach involved further exploration of the aryl carboxylic acid fragment of PNU-282,987, while the second approach focused on modification of the azabicyclic amine portion of PNU-282,987. The best compounds from each series are characterized by rapid brain penetration, good oral bioavailability in rat, and demonstrate in vivo efficacy in a rat P50 auditory sensory gating assay. At least one analog from each series (1h, 1o, 2a, 9a, and 18a) shows an improved hERG safety profile over PNU-282,987.

Arrested chloride abstraction from trans-RuCl2(DMeOPrPE)2 with TlPF6; formation of a 1-D coordination polymer having unusual octahedral coordination around thallium(I).

An "arrested" chloride abstraction occurs in the reaction of trans-RuCl(2)(DMeOPrPE)(2) with TlPF(6); the product is a 1-D coordination polymer in which the Tl(I) centers have an unusual octahedral coordination geometry with a stereochemically active 6s(2) lone pair.

A stereoselective intramolecular 1,3-dipolar nitrone cycloaddition for the synthesis of substituted chromanes.

A stereoselective intramolecular 1,3-dipolar nitrone cycloaddition useful in the synthesis of chromanes is described. The reaction relies on the use of a chiral auxiliary on the nitrone partner. Key to the success of the reaction is the choice of auxiliary and the choice of Lewis acid catalyst. Utilizing an auxiliary with a pendant coordinating group, and Zn(OTf)(2) as the Lewis acid, diastereoselectivities up to 22:1 could be achieved.