Suzuki-Miyaura coupling of aryl iodides, bromides, and chlorides catalyzed by bis(thiazole) pincer palladium complexes.

Bis(thiazole) pincer palladium complexes showed efficient catalytic activity for the Suzuki-Miyaura coupling of aryl halides, allowing the synthesis of biaryls with very high turnover numbers and turnover frequencies. The complexes were successfully applied in the scalable and green synthesis of the key intermediates of bioactive LUF5771 and its analogues.

Effect of Qing Chang oral liquid on the treatment of artificially infected chicken coccidiosis and the cellular immunity.

BACKGROUND: Qing Chang oral liquid (QOL) is a veterinary drug, which mainly composed of Artemisiae annuae herba, Dichroae radix, Agrimonia pilosa and Sanguisorbae radix. OBJECTIVES: This study aims to explore the effect of Qing Chang Oral Liquid (QOL) on the treatment effect of artificially infected chicken coccidiosis and to the cellular immunity. METHODS: Healthy Roman chickens were randomly divided into five groups: blank group, model group, QOL high-, medium- and low-dose groups. All the groups were orally administered with 1 × 104 sporulated oocysts (except the blank group). After 5 days of oral administration, the high-, medium- and low-dose groups of QOL were added to the drinking water at 2.4, 1.8 and 1.2 ml/kg, respectively. The blank and model groups were fed normally, and this experiment lasted for 7 days. The clinical signs were observed, and the relative weight gain, survival rate, cecum lesion score and oocyst value were measured to evaluate the effect of QOL. Meanwhile, the peripheral blood T-lymphocyte subsets and cecal IL-2, IL-17, IFN-γ mRNA expression were detected by flow cytometry and fluorescent quantitative PCR. RESULTS: The chickens in the model group were in poor mental state, gathered together, had loose stools or bloody stools and had less food intake and less exercise. The chicken mental state improved, the food intake and drinking water increased, and the faeces are normal in the high-, medium- and low-dose groups, especially in the high-dose group, the anti-coccidial indexes were up to 173.08. No significant differences were observed (p > 0.05) in the peripheral blood CD3+ , CD3+ CD4+ between the experimental groups. Compared with the blank group, there were different degrees of increase in each dose drug group of the cecal IFN-γ, IL-2 and IL-17 mRNA expression, but the high-dose group was significantly reduced compared with the model group (p < 0.01), but there was no significant difference (p > 0.05). CONCLUSIONS: This study suggests that QOL has positive anti-coccidial effect but has no obvious effect on the cellular immunity.

Hypoxia inducible factor-3α promotes osteosarcoma progression by activating KDM3A-mediated demethylation of SOX9.

Hypoxia/oxygen-sensing signally is closely associated with many tumor progressions, including osteosarcoma (OS). Previous research principally focused on the function of hypoxia-inducible factor (HIF)-1α and HIF-2α as the major hypoxia-associated transcription factors in OS, however, the role of HIF-3α has not been investigated. Our study found that HIF-3α was upregulated in OS tissues and cell lines. HIF-3α overexpression facilitated cell proliferation and invasion, and inhibited apoptosis, whereas HIF-3α knockdown showed the opposite results. Chromatin immunoprecipitation analysis revealed that lysine demethylase 3A (KDM3A) expression was transcriptionally activated by HIF-3α under hypoxia, and KDM3A occupied the SRY-box transcription factor 9 (SOX9) gene promoter region through H3 lysine 9 dimethylation (H3K9me2). Additionally, rescue results revealed that KDM3A or SOX9 overexpression reversed the effects of HIF-3α silence on cell functions. The Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway inhibitor cucurbitacin I suppressed the promotive effects of HIF-3α overexpression on cell proliferation, invasion and TAK2/STAT3 pathway. Finally, OS cell line MG-63 transfected with HIF-3α short hairpin RNA (HIF-3α shRNA) were subcutaneously injected into nude mice, and the results found that HIF-3α knockdown significantly inhibited the xenograft tumor growth of OS in vivo. In conclusion, this study reveals that HIF-3α promotes OS progression in vitro and in vivo by activating KDM3A-mediated SOX9 promoter demethylation, which may provide a potential therapeutic mechanism for OS.

Gastrodia elata attenuates inflammatory response by inhibiting the NF-κB pathway in rheumatoid arthritis fibroblast-like synoviocytes.

Gastrodia elata (GE), which belongs to the Orchidaceae family, was found to possess anti-inflammatory activity. However, the effect of GE on inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) remains largely unknown. Thus, the aim of this study was to investigate the effects of GE on tumor necrosis factor-α (TNF-α)-induced inflammatory response in RA-FLS and the underlying molecular mechanism was also explored. Our results demonstrated that GE significantly attenuated TNF-α-induced IL-6 and IL-8 production in RA-FLS. GE also inhibited TNF-α-induced MMP-3 and MMP-13 expression in RA-FLS. Furthermore, pretreatment with GE significantly attenuated TNF-α-induced the expression of p-p65 and IκBα degradation in RA-FLS. In conclusion, this study demonstrated for the first time that GE attenuated inflammatory response by inhibiting the NF-κB pathway signaling in RA-FLS. Thus, GE might have a therapeutic potential towards the treatment of RA.

Novel bis(azole) pincer palladium complexes: synthesis, structures and applications in Mizoroki-Heck reactions.

Two novel NCN-pincer complex precursors bearing frameworks of 2,6-bis(oxazol-4-yl)benzene (A) and 2-(thiazol-4-yl)-6-(oxazol-4-yl)benzene (B) were synthesized. Palladations of A and B afforded two new bis(azole) pincer complexes, [(A-κ(3)NCN)PdBr] (1) and [(B-κ(3)NCN)PdBr] (2). Both complexes were fully characterized by NMR, MS, DSC-TGA and single-crystal X-ray diffraction analysis. Complex 1 crystallizes in a noncentrosymmetric orthorhombic space group Cmc2(1) (No. 36, Z=4). Complex 2 crystallizes in a centrosymmetric monoclinic space group P2(1)/n (No. 14, Z=4). Despite the similarity in their chemical formulas, the structures of the two complexes are subtly different: they are built up of two-dimensional supramolecular layers with identical topology, but stacked in different sequences, i.e., the layers in complex 1 are stacked in an AAAA-type fashion, while those in complex 2 are stacked in an alternating AA(-1)AA(-1) sequence (A denotes a layer; A(-1) stands for A's inversion symmetry equivalent). In addition, the complexes showed good catalytic activity toward Mizoroki-Heck reactions.