Aloe-emodin targets multiple signaling pathways by blocking ubiquitin-mediated degradation of DUSP1 in nasopharyngeal carcinoma cells.

Aloe-emodin (AE) has been shown to inhibit the proliferation of several cancer cell lines, including human nasopharyngeal carcinoma (NPC) cell lines. In this study, we confirmed that AE inhibited malignant biological behaviors, including cell viability, abnormal proliferation, apoptosis, and migration of NPC cells. Western blotting analysis revealed that AE upregulated the expression of DUSP1, an endogenous inhibitor of multiple cancer-associated signaling pathways, resulting in blockage of the extracellular signal-regulated kinase (ERK)-1/2, protein kinase B (AKT), and p38-mitogen activated protein kinase（p38-MAPK） signaling pathways in NPC cell lines. Moreover, the selective inhibitor of DUSP1, BCI-hydrochloride, partially reversed the AE-induced cytotoxicity and blocked the aforementioned signaling pathways in NPC cells. In addition, the binding between AE and DUSP1 was predicted via molecular docking analysis using AutoDock-Vina software and further verified via a microscale thermophoresis assay. The binding amino acid residues were adjacent to the predicted ubiquitination site (Lys192) of DUSP1. Immunoprecipitation with the ubiquitin antibody, ubiquitinated DUSP1 was shown to be upregulated by AE. Our findings revealed that AE can stabilize DUSP1 by blocking its ubiquitin-proteasome-mediated degradation and proposed an underlying mechanism by which AE-upregulated DUSP1 may potentially target multiple pathways in NPC cells.

Analysis of the clinical features of early Parkinson's disease with comparatively integrated intestinal function.

OBJECTIVE: Constipation is among the most frequently delineated nonmotor symptoms (NMS) with a high occurrence in Parkinson's disease (PD). The purpose of our study was to investigate whether PD with comparatively integrated intestinal function (without constipation) in the early stage had different clinical features compared to constipated PD. METHOD: We conducted a study of 105 consecutive de novo as well as early treated (treated for shorter than 3 months), aged 50 years or older outpatients. Subjects were administered motor and nonmotor questionnaires as well as constipation associated examinations. Then, we explored the distinctive features of nonconstipated contrasted to constipated PD by using univariate, multiple regression analysis and correlation analysis. RESULTS: Nonconstipated PD tended to have fewer motor deficits, as well as lower Hoehn and Yahr (H&Y) stage and they mainly presented as tremor-dominant (TD), while constipated group had a higher occurrence of posture instability and gait difficulty (PIGD); nonconstipated patients were inclined to live in urban area, the NMSloads and prevalence of NMS were lower compared to constipated ones. Correlation analysis found a discord between NMSloads and disease severity based on H&Y stage and motor scores in nonconstipated PD. CONCLUSIONS: These results suggest that PD without constipation in early stage may represent a unique clinical phenotype, which may be more benign than PD with constipation.

Silver-mediated radical coupling reaction of isocyanides and alcohols/phenols in the presence of water: unprecedented hydration and radical coupling reaction sequence.

The radical coupling of isocyanides and alcohols/phenols promoted by silver in the presence of water is reported for the first time, which led to the formation of diverse carbamates. In contrast to the well-known 1,1-addition to form imidoyl radicals, a novel reaction mechanism, involving sequential hydration of isocyanides and coupling with alkoxyl/phenoxyl radicals, is disclosed by combining experimental and theoretical studies.

Silver-catalyzed cascade reaction of tosylmethyl isocyanide (TosMIC) with propargylic alcohols to (E)-vinyl sulfones: dual roles of TosMIC.

An unprecedented silver-catalyzed cascade reaction of tosylmethyl isocyanide (TosMIC) with propargylic alcohols for the efficient synthesis of (E)-vinyl sulfones has been developed where TosMIC plays a dual role as both the reactant in the allenylation of propargylic alcohols and the sulfonyl source.

Chemoselective oxidative C(CO)-C(methyl) bond cleavage of methyl ketones to aldehydes catalyzed by CuI with molecular oxygen.

Aldehyde Termination: A novel copper-catalyzed transformation from methyl ketones into aldehydes has been accomplished. This method is applicable to a wide range of aromatic and aliphatic methyl ketones and chemoselectively produces aldehydes, accompanied by the release of hydrogen (H2 ) and carbon dioxide (CO2 ) as by-products.

DAST-promoted Beckmann rearrangement/intramolecular cyclization of acyclic ketoximes: access to 2-oxazolines, benzimidazoles and benzoxazoles.

The first example of DAST-promoted Beckmann rearrangement/intramolecular cyclization of acyclic ketoximes is described. This unique protocol represents a direct and effective pathway to 2-oxazolines, benzimidazoles and benzoxazoles in moderate to good yields.