Mechanism and Origin of Stereoselectivity for the NHC-Catalyzed Desymmetrization Reaction for the Synthesis of Axially Chiral Biaryl Aldehydes.

Organocatalytic desymmetrization reaction is a powerful tool for constructing axial chirality, but the theoretical study on the origin of stereoselectivity still lags behind even now. In this work, the N-heterocyclic carbene (NHC)-catalyzed desymmetrization reaction of biaryl frameworks for the synthesis of axially chiral aldehydes has been selected and theoretically investigated by using density functional theory (DFT). The fundamental pathway involves several steps, i.e., desymmetrization, formation of Breslow oxidation, esterification, and NHC regeneration. The desymmetrization and formation of Breslow processes have been identified as stereoselectivity-determining and rate-determining steps. Further weak interaction analyses proved that the C-H···O hydrogen bond and C-H···π interactions are responsible for the stability of the key stereoselective desymmetrization transition states. This research contributes to understanding the nature of NHC-catalyzed desymmetrization reactions for the synthesis of axially chiral compounds.

Catalytic asymmetric dearomatization of phenols via divergent intermolecular (3 + 2) and alkylation reactions.

The catalytic asymmetric dearomatization (CADA) reaction has proved to be a powerful protocol for rapid assembly of valuable three-dimensional cyclic compounds from readily available planar aromatics. In contrast to the well-studied indoles and naphthols, phenols have been considered challenging substrates for intermolecular CADA reactions due to the combination of strong aromaticity and potential regioselectivity issue over the multiple nucleophilic sites (O, C2 as well as C4). Reported herein are the chiral phosphoric acid-catalyzed divergent intermolecular CADA reactions of common phenols with azoalkenes, which deliver the tetrahydroindolone and cyclohexadienone products bearing an all-carbon quaternary stereogenic center in good yields with excellent ee values. Notably, simply adjusting the reaction temperature leads to the chemo-divergent intermolecular (3 + 2) and alkylation dearomatization reactions. Moreover, the stereo-divergent synthesis of four possible stereoisomers in a kind has been achieved via changing the sequence of catalyst enantiomers.

Two novel chiral tetranucleate copper-based complexes: syntheses, crystal structures, inhibition of angiogenesis and the growth of human breast cancer in vitro and in vivo.

The single crystals of two novel chiral tetranucleate copper(II)-based complexes (TNCu-A and TNCu-B) containing L-methioninol-derived Schiff-bases were obtained. Their single structures were characterized by X-ray single crystal diffraction, infrared (IR) rays, elemental analysis, and liquid chromatography-mass spectrometry analysis. TNCu-A can effectively inhibit human umbilical vein endothelial cells (HUVECs) to form a tubular structure and it induces apoptosis of human triple-negative breast cancer MDA-MB-231 cells and HUVECs in vitro in a mitochondria dependent manner. Moreover, in vivo TNCu-A can remarkably inhibit the growth of triple-negative breast cancer from which MDA-MB-231 cells were xenografted into severely immunodeficient nude mice by inhibiting proliferation, inducing apoptosis of MDA-MB-231 cells by dramatically inhibiting the expression of the anti-apoptotic protein Bcl-2 and up-regulating the expressions of proapoptotic proteins caspase-9 and Bax, and simultaneously inhibiting tumor angiogenesis by decreasing the density of vascular endothelial cells and suppressing migration and even partially inducing apoptosis.

Fruiting body polysaccharides of Hericium erinaceus induce apoptosis in human colorectal cancer cells via ROS generation mediating caspase-9-dependent signaling pathways.

The fruiting bodies of Hericium erinaceus (Bull.) Pers. are commonly used in China in the treatment of digestive system diseases. In this work, the polysaccharides from the fruiting bodies of Hericium erinaceus (HEFPs) were extracted, and their effects on human colorectal cancer cells (HCT-116 and DLD1) were investigated in vitro. Our results showed that HEFPs were mainly composed of arabinose, galactose, glucose, and mannose at a molar ratio of 8.99 : 11.15 : 1.2 : 1.97. They significantly inhibited the growth of these cells by inducing apoptosis by the modulation of Bax and Bcl-2 expression, which in turn induced the loss of mitochondrial membrane potential, leading to the activation of cleaved-caspase-9 and cleaved-caspase-3. These results suggested that HEFPs induced apoptosis via the caspase-9-depedent intrinsic mitochondrial pathway. Furthermore, HEFPs increased the level of reactive oxygen species (ROS) in HCT-116 and DLD1 cells. The addition of the antioxidant N-acetyl-l-cysteine reduced the ability of HEFPs to trigger the intrinsic mitochondrial pathway, indicating the role of ROS generation in the upstream pathway of HEFP-induced apoptosis. Therefore, the results described in this study could be of interest for further studies in finding functional foods or alternative therapeutic agents against colorectal cancer.

Two novel chiral tetranucleate copper-based complexes: crystal structures, nanoparticles, and inhibiting angiogenesis and the growth of human breast cancer by regulating the VEGF/VEGFR2 signal pathway in vitro.

The single crystals of two novel copper(ii)-based complexes containing l-methioninol-derived Schiff bases were obtained and characterized. The nanoparticles of these complexes were prepared and their cellular uptake was measured in MDA-MB-231 cells and HUVECs. It was found that these complexes could remarkably induce apoptosis, inhibit proliferation, suppress migration and metastasis, and inhibit angiogenesis and the growth of triple-negative breast cancer derived from MDA-MB-231 cells in vitro. Meanwhile, these complexes exhibit anticancer and antiangiogenic functions by activating the important protein molecules VEGFR2, FAK, AKT and Erk1/2 or their phosphorylated molecules p-VEGFR2, p-FAK, p-AKT, and p-Erk1/2 in the VEGF/VEGFR2 signaling pathway, collapsing the mitochondrial membrane potential, and damaging the level of reactive oxygen species.

Isolation and structural characterization of a novel polysaccharide from Hericium erinaceus fruiting bodies and its arrest of cell cycle at S-phage in colon cancer cells.

The fruiting body of Hericium erinaceus has been used to treat digestive system disorder-related diseases for over 2000 years in China. A novel polysaccharide, HEFP-2b, was obtained from H. erinaceus fruiting bodies. Physical and chemical analysis showed that HEFP-2b consisted of fucose, galactose, glucose, and mannose in molar ratio of 11.81:22.82:44.28:21.09, and that its molecular weight was 3.252 × 104 Da. The backbone of HEFP-2b consisted of →6)-linked-α-D-Glcp-(1→ and →4)-ß-D-Galp-(1→ and →3,6) -α-D-Manp linkage, with two side-branching units of (1→ and →6)-ß-D-Galp and (1→ and →4)-α-D-Manp, terminated by Glc and Fuc. The results of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell cycle arrest experiments revealed that HEFP-2b considerably inhibited the growth of colon cancer cells (HCT-116) in vitro. The growth inhibitory effects of HEFP-2b correlated with their ability to arrest the cell cycle at the S-phase. Our results will provide valuable information for future studies on HEFP-2b as a novel health-promoting functional food ingredient that can be used for treating colon cancer.

Aryl Hydrocarbon Receptor Modulates the Expression of TNF-α and IL-8 in Human Sebocytes via the MyD88-p65NF-κB/p38MAPK Signaling Pathways.

Activation of Toll-like receptor (TLR)-2 and subsequent inflammatory response contribute to lesion development in acne vulgaris. A cross-talk between aryl hydrocarbon receptor (AhR), a cytosolic receptor protein that responds to environmental and physiological stress, and TLRs has recently been reported. In this study, we explored the possible role of AhR in the effects induced on cultured human SZ95 sebocytes by peptidoglycan (PGN), a classic TLR2 agonist. PGN-induced secretion of inflammatory factors TNF-α and IL-8 in human SZ95 sebocytes was suppressed after knockdown of AhR and pretreatment with the AhR antagonist CH223191. In addition, the AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) enhanced TNF-α and IL-8 secretion in PGN-pretreated sebocytes. Furthermore, PGN-induced expression of myeloid differentiation factor 88 (MyD88), phospho-p38MAPK (p-p38MAPK), and p-p65NF-κB was strengthened by TCDD and repressed by CH223191. AhR inhibition by transfecting shRNA blocked the ability of PGN to stimulate phosphorylation of p38MAPK and p65NF-κB in SZ95 sebocytes. Overall, these data demonstrate that AhR is able to modulate PGN-induced expression of TNF-α and IL-8 in human SZ95 sebocytes involving the MyD88-p65NF-κB/p38MAPK signaling pathway, which probably indicates a new mechanism in TLR2-mediated acne.

Is Human Sebum the Source of Skin Follicular Ultraviolet-Induced Red Fluorescence? A Cellular to Histological Study.

BACKGROUND: The ultraviolet-induced red fluorescence (UVRF) from human skin follicles was suggested to be a result of Propionibacterium acnes and was used for the monitoring of acne. More recent studies suggested that the UVRF may be more related to sebum rather than to microorganisms. OBJECTIVE: To clarify whether human sebum or follicular microorganisms are the source of UVRF. METHODS: We examined the fluorescence of human-derived SZ95 sebocytes, human sebaceous glands, sebum extracted from the sebaceous glands, and bacteria isolated from human hair follicles under ultraviolet light. RESULTS: SZ95 sebocytes, human sebaceous glands, and sebum do not emit UVRF. Two types of UVRF peaking at about 635 nm and at about 620 nm were detected in P. acnes and Staphylococcus epidermidis, respectively. This is the first report that S. epidermidis emits UVRF when it is anaerobically cultured and then exposed to air. CONCLUSION: Human follicular UVRF is emitted by resident bacteria, not by sebum. Therefore, UVRF may be used to monitor certain species of skin microorganisms.

Effects of methylthiouracil on the proliferation and apoptosis of rat bone marrow stromal cells.

The aim of the present study was to investigate the effects of methylthiouracil (MTU) on the proliferation and apoptosis of rat bone marrow stromal cells (BMSCs). Rat BMSCs were isolated, cultured in vitro and treated with various concentrations of MTU. Cell growth curves were determined using the Cell Counting Kit-8 method and the effect of MTU on BMSCs in a logarithmic growth phase was observed. BMSC apoptosis following MTU treatment was detected by flow cytometry. The experimental results demonstrated that the proliferation-inhibition effect was gradually enhanced with increasing MTU concentrations and the extension of treatment time. Statistically significant differences were observed between the treatment and the control groups (P<0.05). In addition, the BMSC apoptosis rate gradually increased with increasing drug concentrations and treatment time extension; statistically significant differences were observed between the treatment and the control groups (P<0.05). Therefore, the results of the present study demonstrated that MTU inhibited the proliferation of BMSCs and promoted apoptosis, indicating the cytotoxic effects of MTU on BMSCs.

Electrospun curcumin-loaded fibers with potential biomedical applications.

Polyvinyl alcohol (PVA) nanofibers loaded with curcumin or its ß-cyclodextrin (CD) inclusion complex were successfully prepared using an electrospinning process. The influence of curcumin or CD-curcumin complex content on fiber formation and quality was investigated. X-ray diffraction and differential scanning calorimetry analyses of the fibers, together with electron microscope evidence, demonstrated that curcumin is likely to be present as crystalline aggregates in the fibers, while its CD complex is more evenly distributed. (1)H NMR analysis indicated that the chemical structure of curcumin was preserved during the electrospinning process. Thermogravimetric analysis demonstrated that inclusion into nanofibers enhanced the thermal stability of curcumin. In vitro dissolution tests showed that the drug release profiles of the PVA/curcumin and PVA/complex fibers were different, with release from the latter occurring more rapidly. Release from both fiber types was found to be largely governed by a diffusion-controlled mechanism; two sequential stages for drug release were observed.

[Effect of HPV 16 E5 on E6 and E7 gene induced human immortalized oral epithelial cell].

PURPOSE: To investigate the influence of HPV16 E5 on E6 and E7 gene in human oral immortalized epithelial cells (HIOEC). METHODS: The pLEGFP-E5 was transferred into HIOEC cell; Deletion mutation expression vectors were constructed and transferred into HIOEC; RT-PCR was used to detect the gene expression in HIOEC; The expression of E6 and E7 mRNA was detected by real time-PCR;Cell proliferation of HIOEC was evaluated by MTT. All statistical analysis was performed by using SPSS 13.0 software package. RESULTS: The deletion mutation expression vector of E5 was successfully constructed and applied for further experiments; E5 and the deletion mutation genes were transferred into HIOEC successfully; HPV16 E5 promoted cell proliferation of HIOEC and made the increased expression raised of E6 and E7 genes; However, the deletion mutation had no significant effect on HIOEC. CONCLUSIONS: HPV16 E5 is transferred into HIOEC successfully. E5 may promote cell proliferation and upregulate the mRNA expression of E6 and E7 genes.