N-Trifluoromethylselenophthalimide, an Electrophilic Trifluoromethylselenolation Reagent and Its Application for the Synthesis of 4-Trifluoromethylselenolated Isoxazoles.

A new electrophilic trifluoromethylselenolation reagent, N-trifluoromethylselenophthalimide (Phth-SeCF3), was developed. A strategy for the synthesis of 4-trifluoromethylselenolated isoxazoles through electrophilic trifluoromethylselenolation cyclization has been established by using Phth-SeCF3 as an electrophilic reagent. Moreover, this protocol has the features of broad substrate scope, good functional group tolerance, and high yields.

Synthesis of Spiro[5.5]trienones- and Spiro[4.5]trienones-Fused Selenocyanates via Electrophilic Selenocyanogen Cyclization and Dearomative Spirocyclization.

A practical strategy for the synthesis of spiro[5.5]trienones-fused selenocyanates and spiro[4.5]trienones-fused selenocyanates through electrophilic selenocyanogen cyclization and dearomative spirocyclization is reported. This approach was conducted under mild conditions with broad substrate scope and good functional group tolerance. The utility of this procedure is exhibited in the late-stage functionalization of nature product and drug molecules.

TNF-α-Producing Cryptococcus neoformans Exerts Protective Effects on Host Defenses in Murine Pulmonary Cryptococcosis.

Tumor necrosis factor alpha (TNF-α) plays a critical role in the control of cryptococcal infection, and its insufficiency promotes cryptococcal persistence. To explore the therapeutic potential of TNF-α supplementation as a booster of host anti-cryptococcal responses, we engineered a C. neoformans strain expressing murine TNF-α. Using a murine model of pulmonary cryptococcosis, we demonstrated that TNF-α-producing C. neoformans strain enhances protective elements of host response including preferential T-cell accumulation and improved Th1/Th2 cytokine balance, diminished pulmonary eosinophilia and alternative activation of lung macrophages at the adaptive phase of infection compared to wild type strain-infected mice. Furthermore, TNF-α expression by C. neoformans enhanced the fungicidal activity of macrophages in vitro. Finally, mice infected with the TNF-α-producing C. neoformans strain showed improved fungal control and considerably prolonged survival compared to wild type strain-infected mice, but could not induce sterilizing immunity. Taken together, our results support that TNF-α expression by an engineered C. neoformans strain while insufficient to drive complete immune protection, strongly enhanced protective responses during primary cryptococcal infection.

[Expression of NLRP3 inflammasome in BALB/c mice with imiquimod-induced psoriasis-like inflammation and therapeutic effect of mustard seed (Sinapis Alba Linn)].

OBJECTIVE: To investigate the role of NLRP3 inflammasome in imiquimod-induced psoriasis-like inflammation in mice and the therapeutic effects of mustard seed (Sinapis Alba Linn). METHODS: Thirty BALB/c mice were randomized equally into blank control group (fed with normal forage and treated with vehicle), model group (fed with normal forage and treated with 5% imiquimod cream), and experimental group (fed with 5% mustard seed forage and treated with 5% imiquimod cream). RT-PCR was used to detect the mRNA expression of NLRP3, ASC, caspase-1, and caspase-11. Immunohistochemistry was performed to determine the expression and distribution of ASC and caspase-1. ELISA was used to test the serum levels of interleukin-1ß (IL-1ß) and IL-18. RESULTS: Compared with the blank control group, the mice with imiquimod-induced psoriasis-like inflammation showed significantly increased NLRP3, ASC, caspase-1, and caspase-11 mRNA expressions, ASC and caspase-1 protein expressions , and serum levels of IL-1ß and IL-18 (P<0.05). These changes were obviously attenuated by feeding the mice with mustard seed. CONCLUSION: NLRP3 inflammasome is involved in imiquimod-induced psoriasis-like inflammation in mice, and mustard seed may suppress the inflammation induced by IL-1ß and IL-18 through down-regulating the expression of NLRP3 inflammasome.

Mustard seed (Sinapis Alba Linn) attenuates imiquimod-induced psoriasiform inflammation of BALB/c mice.

Psoriasis is a chronic inflammatory autoimmune disease with undefined etiology. All present treatments are symptomatic. The unsatisfactory outcome in the treatment of psoriasis is partially due to the poor compliance to the present therapies with more or less side-effects. As is known, drug homologous food is a popular intervention of some chronic diseases in Chinese traditional medicine. Mustard seed, consumed largely as a spice and a medicine in China, has recently been found to possess the bioactivities of anti-oxidation, anti-inflammation and anticancer. Therefore, it was supposed that mustard seed may have effects on psoriasis, and it was preliminarily validated using a BALB/c mouse model of psoriasiform inflammation induced by the topical application of imiquimod cream (Aldara) for 6 days consecutively. It was found that the forage containing 5% mustard seed obviously attenuated imiquimod-induced psoriasiform inflammation, but did not clear it completely, accompanied by reduced infiltrations of T cells, plasmacytoid dendritic cells (pDC) and macrophages in lesional skin; reduced percentages of pDC and macrophages in the composition of immunocytes of spleens; reduced content of lesion nuclear factor-κB p65, plasma malondialdehyde, lesion inducible nitric oxide synthase, interferon-α, interleukin (IL)-17 and IL-22 at mRNA and protein levels; increased activities of superoxide dismutase, catalase and glutathione peroxidase; and increased percentage of CD4(+) T cells and increased ratio of CD4(+) /CD8(+) T cells in the composition of immunocytes of spleen. These results presented herein provide a basis for mustard seed to be used as a promising intervention for psoriasis in the future.

[Effects of mustard seed on 2, 4-dinitrofluorobenzene-induced allergic contact dermatitis in BALB/c mice].

OBJECTIVE: To investigate the therapeutic effect of mustard seed on allergic contact dermatitis (ACD) in mice and explore the mechanism. METHODS: Eighteen BALB/c mice were randomly divided into normal control group, model group and mustard seed group. The mice in the normal control group and model group were fed with normal chow, and those in mustard seed group were given 5% mustard seed mixed in the chow. Three weeks later, ACD was induced on the ear using 2, 4-dinitrofluorobenzene. After 24 h, the swelling of the ear was examined, and the rats were sacrificed to collect the ear tissue ears and blood for histopathological and immunohistochemical examinations, RT-PCR and enzyme-linked immunosorbent assay. RESULTS: In mice with ACD, feeding with mustard seeds significantly lessened the ear swelling, improved the tissue histopathology, lowered the number of infiltrating Langerhans cells, and reduced the expressions of IL-1ß, TNF-α and IL-6 mRNA in the ear, but did not cause significant changes in serum levels of IL-4, IFN-γ and IL-17. CONCLUSION: Mustard seed inhibits ACD in mice possibly by suppressing the expressions of IL-1ß, TNF-α and IL-6 mRNA and inhibiting Langerhans cell migration in the epidermis.