Design and Synthesis of MarinePolybrominated Diphenyl Ether Derivatives as Potential Anti-inflammatory Agents.

Natural polybrominated diphenyl ethers are generally isolated from sponges and possess a broad range of biological activities. Through screening of our marine natural product library, we discovered that polybrominated diphenyl ethers 5 and 6 exhibit considerable anti-inflammatory activity. In order to expand our repertoire of derivatives for further biological activity studies, we designed and synthesized a series of 5-related polybrominated diphenyl ethers. Importantly, compound 5a showed comparable anti-inflammatory activity while much lower cytotoxicity on lipopolysaccharide (LPS)-induced RAW264.7 cells. Additionally, western blotting analysis showed that 5a reduced the expression of phosphorylated extracellular signal-regulated kinase (p-ERK). Besides, molecular docking experiments were conducted to predict and elucidate the potential mechanisms underlying the varying anti-inflammatory activities exhibited by compounds 5a, 5, and 6.

New Glycerolipids from the Traditional Chinese Medicine of Syngnathus acus (Hai-Long).

Two new glycerolipids, syngaculipids A and B (1 and 2), one first naturally occurring metabolite (8), together with five known compounds (3-7) were isolated from the AcOEt fraction of Syngnathus acus L. (Hai-Long). Their structures were elucidated by comprehensive spectral analyses involving UV, IR, MS, 1D and 2D NMR spectra and ECD calculations. All the isolated compounds were evaluated for their cytotoxicity against A549 and HCT-116 cell lines. Compound 8 exhibited moderate cytotoxicity with IC50 values of 34.5 and 38.9 µM on the A549 and HCT-116 cell lines, respectively.

[Effects of Different Colored Polycarbonate Plastics on Growth and Community Structure of Periphytic Algae].

Periphytic algae are important primary producers in water bodies, which play an important role in maintaining ecological function and water purification. Previous studies have shown that plastic is a good substrate for periphytic algae, and different plastic materials have different effects on the colonization of periphytic algae; however, there are few reports on the effects of plastic color on the growth of periphytic algae. In this study, polycarbonate plastic (PC) of various colors were used as the substrate to study the effects of different colors on the growth and community structure of periphytic algae by measuring the biomass, photosynthetic activity, and community composition. The results showed that the growth of periphytic algae was inhibited by the brown PC plastic, and the contents of chlorophyll a and dry weight in this group were significantly lower than those in other groups. Green PC plastic inhibited the photosynthetic activity of periphytic algae, and the actual photosynthetic efficiency (Yield) of the group was significantly lower than that of the other groups. The influence of PC plastic with different colors on periphytic algae occurred mainly in the early colonization/development stage but was not significant in the late community maturity stage. On day seven of the experiment, the community composition of periphytic algae was significantly different between the transparent PC plastic group and the green PC plastic group. By contrast, on days 25 and 40, there were no significant differences in the community structure of periphytic algae. In the early stage of the experiment, the dominant genus was Pseudoranea (Cyanophyta), and in the middle and mature stages, the dominant genus was Mougeotia (Chlorophyta). In this study, the effects of different colors of polycarbonate plastics on periphytic algae were investigated, which provided new insights for selecting suitable substrates for water pollution treatment by using periphyton biotechnology.

Curcumin alleviates experimental colitis via a potential mechanism involving memory B cells and Bcl-6-Syk-BLNK signaling.

BACKGROUND: Immune dysfunction is the crucial cause in the pathogenesis of inflammatory bowel disease (IBD), which is mainly related to lymphocytes (T or B cells, incl-uding memory B cells), mast cells, activated neutrophils, and macrophages. As the precursor of B cells, the activation of memory B cells can trigger and differentiate B cells to produce a giant variety of inducible B cells and tolerant B cells, whose dysfunction can easily lead to autoimmune diseases, including IBD. AIM: To investigate whether or not curcumin (Cur) can alleviate experimental colitis by regulating memory B cells and Bcl-6-Syk-BLNK signaling. METHODS: Colitis was induced in mice with a dextran sulphate sodium (DSS) solution in drinking water. Colitis mice were given Cur (100 mg/kg/d) orally for 14 con-secutive days. The colonic weight, colonic length, intestinal weight index, occult blood scores, and histological scores of mice were examined to evaluate the curative effect. The levels of memory B cells in peripheral blood of mice were measured by flow cytometry, and IL-1ß, IL-6, IL-10, IL-7A, and TNF-α expression in colonic tissue homogenates were analyzed by enzyme-linked immunosorbent assay. Western blot was used to measure the expression of Bcl-6, BLNK, Syk, and other signaling pathway related proteins. RESULTS: After Cur treatment for 14 d, the body weight, colonic weight, colonic length, colonic weight index, and colonic pathological injury of mice with colitis were ameliorated. The secretion of IL-1ß, IL-6, TNF-α, and IL-7A was statistically decreased, while the IL-35 and IL-10 levels were considerably increased. Activation of memory B cell subsets in colitis mice was confirmed by a remarkable reduction in the expression of IgM, IgG, IgA, FCRL5, CD103, FasL, PD-1, CD38, and CXCR3 on the surface of CD19+ CD27+ B cells, while the number of CD19+ CD27+ IL-10+ and CD19+ CD27+ Tim-3+ B cells increased significantly. In addition, Cur significantly inhibited the protein levels of Syk, p-Syk, Bcl-6, and CIN85, and increased BLNK and p-BLNK expression in colitis mice. CONCLUSION: Cur could effectively alleviate DSS-induced colitis in mice by regulating memory B cells and the Bcl-6-Syk-BLNK signaling pathway.

Ginsenoside Rg1 ameliorated experimental colitis by regulating the balance of M1/M2 macrophage polarization and the homeostasis of intestinal flora.

Aberrant M1/M2 macrophage polarization and dysbiosis are involved in the pathogenesis of ulcerative colitis (UC). Ginsenoside Rg1 exhibits optimal immunomodulatory and anti-inflammatory effects in treating UC of humans and animals, but the action mechanism through the regulation of M1/M2 macrophage polarization and intestinal flora composition remain unclear. Here, experimental colitis was induced in BALB/c mice using dextran sulfate sodium, and Rock1 inhibitor Y27632 was used to explore the action mechanism of ginsenoside Rg1. Following treatment with ginsenoside Rg1 (200 mg/kg/day) and Y27632 (10 mg/kg/day) for 14 consecutive days, the rate of change in mouse body weight, mouse final weight, colonic weight, colonic length, colonic weight index and pathological damage scores of colitis mice were effectively improved, accompanied by less ulcer formation and inflammatory cell infiltration, lower levels of interleukin (IL)-6, IL-33, chemokine (C-C motif) ligand 2 (CCL-2), tumor necrosis factor alpha (TNF-α), and higher IL-4 and IL-10. Importantly, ginsenoside Rg1 and Y27632 significantly down-regulated CD11b+F4/80+, CD11b+F4/80+Tim-1+ and CD11b+F4/80+TLR4+ macrophages, and CD11b+F4/80+iNOS+ M1 macrophages, and significantly up-regulated CD11b+F4/80+CD206+ and CD11b+F4/80+CD163+ M2 macrophages in colitis mice; concomitantly, ginsenoside Rg1 improved the diversity of colonic microbiota and regulated Lachnospiraceae, Staphylococcus, Bacteroide and Ruminococcaceae_UCG_014 at genus level in colitis mice, but the flora regulated by Y27632 was not identical to it. Moreover, ginsenoside Rg1 and Y27632 down-regulated the protein levels of Rock1, RhoA and Nogo-B in colitis mice. These results suggested that ginsenoside Rg1 and Y27632 ameliorated colitis by regulating M1/M2 macrophage polarization and microbiota composition, associated with inhibition of the Nogo-B/RhoA signaling pathway.

Curcumin Alleviated Dextran Sulfate Sodium-Induced Colitis by Regulating M1/M2 Macrophage Polarization and TLRs Signaling Pathway.

Curcumin has shown good efficacy in mice with experimental colitis and in patients with ulcerative colitis, but the mechanism of action through the regulation of M1/M2 macrophage polarization has not been elaborated. The ulcerative colitis was modeled by dextran sulfate sodium; colitis mice were orally administrated with curcumin (10 mg/kg/day) or 5-ASA (300 mg/kg/day) for 14 consecutive days. After curcumin treatment, the body weight, colon weight and length, colonic weight index, and histopathological damage in colitis mice were effectively improved. The concentrations of proinflammatory cytokines IL-1ß, IL-6, and CCL-2 in the colonic tissues of colitis mice decreased significantly, while anti-inflammatory cytokines IL-33 and IL-10 increased significantly. Importantly, macrophage activation was suppressed and M1/M2 macrophage polarization was regulated in colitis mice, and the percentage of CD11b+F4/80+ and CD11b+F4/80+TIM-1+ and CD11b+F4/80+iNOS+ decreased significantly and CD11b+F4/80+CD206+ and CD11b+F4/80+CD163+ increased significantly. Additionally, curcumin significantly downregulated CD11b+F4/80+TLR4+ macrophages and the protein levels of TLR2, TLR4, MyD88, NF-κBp65, p38MAPK, and AP-1 in colitis mice. Our study suggested that curcumin exerted therapeutic effects in colitis mice by regulating the balance of M1/M2 macrophage polarization and TLRs signaling pathway.

[Toxicological Effects of Enrofloxacin and Its Removal by Freshwater Micro-Green Algae Dictyosphaerium sp.]

Enrofloxacin (ENR), a fluoroquinolones antibiotic, is widely used in the medical and aquaculture fields. Its residues in surface waters in China are high. However, few studies have evaluated both its toxicity to phytoplankton and the degradation or removal by microalgae. In this study, the growth, photosynthetic activity, and exopolysaccharides (EPS) of freshwater micro-green algae Dictyosphaerium sp. and the dynamics of ENR concentrations (0, 5, 25, 50, and 100 mg·L-1) were studied through an exposure experiment for 12 days. Results showed that the biomass and photosynthetic pigment content of Dictyosphaerium sp. increased with increasing exposure time in each treatment; however, it showed a significant inhibitory effect on the growth and pigment accumulation of Dictyosphaerium sp. compared with the control group (P<0.01). The LC50 of ENR to Dictyosphaerium sp. was (241.29±7.33) mg·L-1 after 96-h exposure, indicating that Dictyosphaerium sp. could adapt to the stress conditions of high concentration ENR. Meanwhile, when the concentration of enrofloxacin was<5 mg·L-1, it was found to promote the maximum photosynthetic rate (Fv/Fm) of Dictyosphaerium sp. On the contrary, when the concentration of enrofloxacin was>5 mg·L-1, photosynthetic inhibition was observed (P<0.01). The actual photosynthetic rate (Yield) and the maximum electron transfer rate (ETRmax) showed a trend of initially decreasing and then increasing in 12 days. It can gradually adapt to the stress conditions and recover certain photosynthetic activity after 6 days' exposure. In addition, ENR can also stimulate the EPS (RPS and CPS) release. At the end of the experiment, the removal rates of ENR in the four control groups (no algae addition groups) (5, 25, 50, and 100 mg·L-1ENR) were 7.27%, 5.56%, 5.30%, and 4.88%, respectively, while the removal rates of the treatment groups were 3.21, 3.01, 2.69, and 2.83 times of the no algae groups, indicating that Dictyosphaerium sp. had a significant promoting effect on the removal of ENR (P<0.01). Overall, our results can provide new insights for the understanding of the ecological toxicity of fluoroquinolone antibiotics to primary producers in the aquatic system and also provide new ideas for the ecological removal of antibiotic residues in water bodies and the biological resource utilization of freshwater microalgae.

Synthesis of 2,3-Dihydrothieno(2,3-b)quinolines and Thieno(2,3-b)- quinolines via an Unexpected Domino Aza-MBH/Alkylation/Aldol Reaction.

An efficient, mild, and convenient method for the preparation of 2,3-dihydrothieno(2,3-b)quinolines and thieno(2,3-b)-quinolines via an unexpected domino aza-Morita-Baylis-Hillman/alkylation/aldol reaction has been developed. The plausible mechanisms for the unexpected reaction are also given.