Inhibition of LPMOs by Fermented Persimmon Juice

Fermented persimmon juice, Kakishibu, has traditionally been used for wood and paper protection. This protective effect stems at least partially from inhibition of microbial cellulose degrading enzymes. The inhibitory effect of Kakishibu on lytic polysaccharide monooxygenases (LPMOs) and on a cocktail of cellulose hydrolases was studied, using three different cellulosic substrates. Dose dependent inhibition of LPMO activity by a commercial Kakishibu product was assessed for the well-characterized LPMO from Thermoascus aurantiacus TaAA9A, and the inhibitory effect was confirmed on five additional microbial LPMOs. The model tannin compound, tannic acid exhibited a similar inhibitory effect on TaAA9A as Kakishibu. It was further shown that both polyethylene glycol and tannase can alleviate the inhibitory effect of Kakishibu and tannic acid, indicating a likely mechanism of inhibition caused by unspecific tannin–protein interactions.

Acupoint Autohemotherapy Attenuates DNCB-induced Atopic Dermatitis Lesions by Regulating Th1/Th2 Cytokine Balance in BALB/c Mice

Objective Acupoint autohemotherapy (A-AHT) is considered an effective therapy for atopic dermatitis (AD) with few side-effects. Previous experiments showed the treatment had the potential to regulate T helper (Th) 1 and Th2 cytokines, like interferon (IFN)- gamma and interleukin (IL)- 4. This study focuses on the effects of A-AHT on the AD-like skin lesions through regulating Th1/Th2 immune responses. Methods The treatments of A-AHT, sham acupoint autohemotherapy and acupoint injection of normal saline were administered in the AD mice once every other day for 4 weeks. The total immunoglobulin (Ig) E, IL-4 and IFN-γ cytokine levels in the serum were examined after animal sacrifice. Th1/Th2 expression was analyzed in murine spleen cells via flow cytometry and immunohistochemical analysis of GATA-3 and T-bet in skin lesions were further assessed. Results Either type of repeated autologous whole blood (AWB) injection (into acupoint or sham acupoint) reduced the severity of AD-like symptoms and level of serum IgE. All of the three treatments had the similar inhibitory effect on levels of IL-4 and upregulation on the ratio of IFN-γ/IL-4, while differed on Th1/Th2 ratio as A-AHT regulates the body’s Th1/Th2 shift. This treatment also increased the related transcription factors T-bet expression, and upregulated T-bet/GATA3 ratio compared with the DNCB group. These differences were significant only in A-AHT group. Conclusion A-AHT effectively reduces AD symptoms and serum IgE levels in a mouse model and may act by regulating Th1/Th2 immune responses.

Proteolytic Activity in Meadow Soil after the Application of Phytohormones

Phytohormones, similar to soil enzymes, are synthesized and secreted into the soil environment by fungi and microorganisms. Phytohormones are involved in regulating microbial community activity in the rhizosphere. This paper examines how auxins, cytokinins, ethephon and chlorocholine chloride affect the activity of native soil proteases in the organo-mineral horizon of an alpine meadow. In the meadow habitat, native soil proteases were inhibited by auxins whereas the effect of cytokinins on these enzymes was not statistically significant. A similar inhibitory effect on the activity of proteases was shown for ethephon and chlorocholine chloride, both of which also inhibited the activity of native soil proteases in the alpine meadow soil. Overall, the inhibitory effect of phytohormones on the activity of native protease activity may affect plant nutrition by retarding the nitrogen cycle in the soil. This work contributes to our understanding of the influence of substances produced by the rhizosphere that can actively participate in the activity of soil microorganisms and consequently influence the soil nitrogen cycle.

Glucose Metabolism byEscherichia coliInhibitsVibrio choleraeIntestinal Colonization of Zebrafish

ABSTRACTTheVibrio choleraeO1 serogroup is responsible for pandemic cholera and is divided into the classical and El Tor biotypes. ClassicalV. choleraeproduces acid when using glucose as a carbon source, whereas El TorV. choleraeproduces the neutral product acetoin when using glucose as a carbon source. An earlier study demonstrated thatEscherichia colistrains that metabolize glucose to acidic by-products drastically reduced the survival ofV. choleraestrainsin vitro. In the present study, zebrafish were fed 1% glucose and either inoculated with singleV. choleraeorE. colistrains or coinfected with bothV. choleraeandE. coli. A significant decrease in classical biotype colonization was observed after glucose feeding due to acid production in the zebrafish intestine. El Tor colonization was unaffected by glucose alone. However, the El Tor strain exhibited significantly lower colonization of the zebrafish when either of the acid-producingE. colistrains was coinoculated in the presence of glucose. AnE. colisugar transport mutant had no effect onV. choleraecolonization even in presence of glucose. Glucose andE. coliproduced a prophylactic effect on El Tor colonization in zebrafish whenE. coliwas inoculated beforeV. choleraeinfection. Thus, the probiotic feeding ofE. coliinhibitsV. choleraecolonization in a natural host. This suggests that a similar inhibitory effect could be seen in cholera patients, especially if a glucose-based oral rehydration solution (ORS) is administered in combination with probioticE. coliduring cholera treatment.

Characterization of Plasmodium Atg3-Atg8 Interaction Inhibitors Identifies Novel Alternative Mechanisms of Action in Toxoplasma gondii

ABSTRACT Protozoan parasites, including the apicomplexan pathogens Plasmodium falciparum (which causes malaria) and Toxoplasma gondii (which causes toxoplasmosis), infect millions of people worldwide and represent major human disease burdens. Despite their prevalence, therapeutic strategies to treat infections caused by these parasites remain limited and are threatened by the emergence of drug resistance, highlighting the need for the identification of novel drug targets. Recently, homologues of the core autophagy proteins, including Atg8 and Atg3, were identified in many protozoan parasites. Importantly, components of the Atg8 conjugation system that facilitate the lipidation of Atg8 are required for both canonical and parasite-specific functions and are essential for parasite viability. Structural characterization of the P. falciparum Atg3-Atg8 (PfAtg3-Atg8) interaction has led to the identification of compounds that block this interaction. Additionally, many of these compounds inhibit P. falciparum growth in vitro, demonstrating the viability of this pathway as a drug target. Given the essential role of the Atg8 lipidation pathway in Toxoplasma, we sought to determine whether three PfAtg3-Atg8 interaction inhibitors identified in the Medicines for Malaria Venture Malaria Box exerted a similar inhibitory effect in Toxoplasma. While all three inhibitors blocked Toxoplasma replication in vitro at submicromolar concentrations, they did not inhibit T. gondii Atg8 (TgAtg8) lipidation. Rather, high concentrations of two of these compounds induced TgAtg8 lipidation and fragmentation of the parasite mitochondrion, similar to the effects seen following starvation and monensin-induced autophagy. Additionally, we report that one of the PfAtg3-Atg8 interaction inhibitors induces Toxoplasma egress and provide evidence that this is mediated by an increase in intracellular calcium in response to drug treatment.

Resveratrol Inhibits Propagation ofChlamydia trachomatisin McCoy Cells

Resveratrol (RESV), an antifungal compound from grapes and other plants, has a distinct ability to inhibit theChlamydia (C.) trachomatisdevelopmental cycle in McCoy cells, a classic cell line used for chlamydial research. Inoculation ofC. trachomatiswith increasing amounts of RESV (from 12.5 to 100 μM) gave a dose-dependent reduction in the number of infected McCoy cells visualized by using monoclonal antibodies against chlamydial lipopolysaccharide. A similar trend has been observed with immunoassay for major outer membrane protein (MOMP). Furthermore, there was a step-wise reduction in the number ofC. trachomatisinfective progenies caused by the increasing concentrations of RESV. The ability of RESV to arrestC. trachomatisgrowth in McCoy cells was confirmed by a nucleic acid amplification protocol which revealed dose-dependent changes in mRNAs for different genes of chlamydial developmental cycle (euo,incA, andomcB). Although the precise nature of the antichlamydial activity of RESV is yet to be determined and evaluated in future studies, the observed effect of RESV onC. trachomatisinfection was not related to its potential effect on attachment/entry of the pathogen into eukaryotic cells or RESV toxicity to McCoy cells. Similar inhibitory effect was shown forC. pneumoniaeandC. muridarum.

Toxicity of coke wastewater treated with advanced oxidation by Fenton process supported by ultrasonic field

The aim of the presented study was to determine the toxicity of wastewater from the production of coke. The wastewater was treated with advanced oxidation involving ultrasonic field with Fenton’s reagent (the amplitude was 61.5 μm and sonication time 8 min). Two doses of iron and four doses of hydrogen peroxide were used. The amount of hydrogen peroxide was proportional to the value of the chemical oxygen demand of raw wastewater, ranging from COD/H2O2 ratio of 1:2.5 to 1:20. Two tests were used to determine the toxicity (algae growth inhibition test and Lepidium test). It was found that more toxic to algae was wastewater treated by Fenton’s reagent containing a higher dose of iron. A similar inhibitory effect was observed on the germination of cress seeds.

Effect of 1-MCP and O3 on the Qualities of Dendrobium Officinale Storage

The aim of this work to evaluate the influence of 1-MCP, O3and 1-MCP+O3to Dendrobium officinale. 1-MCP could inhibit plants respiration rate, and it was 14.57 mg CO2·kg·FW·h-for 7 days which lower than CK and O3had similar inhibitory effect to respiration.1-MCP, O3could inhibit weight loss and O3was more significant than 1-MCP, but 1-MCP+O3treatments weight loss was similar to CK for 60 days, however 1-MCP+O3had significant effect on color change, it could inhibit color change during storage for plants.

New α-Glucosidase Inhibitory Polysaccharides Isolated from Marine Green Algae Enteromorpha Linza

The crude polysaccharides were extracted by hot water from marine green algae Enteromorpha linza. After that, five polysaccharides were obtained through Q-Sepharose Fast Flow chromatography. Their structures and monosaccharide compositions were analyzed by FTIR and GC-MS. Mannose was the abundant monosaccharide in both ELP-3 and ELP-4. ELP-3 consisted of mannose, L(-)-fucose, D-glucose, D-galactose, D-arabinose and D-xylose in a molar ratio of 1.00:0.66:0.46:0.41:0.27:0.19. In α-glucosidase inhibition assay, the polysaccharides showed significant inhibitory activities. ELP-3 (IC50 =0.36 mg/mL) exhibited much stronger inhibitory effect against α-glucosidase, compared with Acarbose (IC50=0.46 mg/mL), while ELP-4, a similar inhibitory effect (IC50=0.58 mg/mL) as Acarbose. Moreover, it was found that EPLs have moderate antioxidant activities in 1,1-diphenyl-2-picrylhydrazil (DPPH) scavenging experiment.

Inhibition of glutaminyl cyclase attenuates cell migration modulated by monocyte chemoattractant proteins

QC (glutaminyl cyclase) catalyses the formation of N-terminal pGlu (pyroglutamate) in peptides and proteins. pGlu formation in chemoattractants may participate in the regulation of macrophage activation and migration. However, a clear molecular mechanism for the regulation is lacking. The present study examines the role of QC-mediated pGlu formation on MCPs (monocyte chemoattractant proteins) in inflammation. We demonstrated in vitro the pGlu formation on MCPs by QC using MS. A potent QC inhibitor, PBD150, significantly reduced the N-terminal uncyclized-MCP-stimulated monocyte migration, whereas pGlu-containing MCP-induced cell migration was unaffected. QC small interfering RNA revealed a similar inhibitory effect. Lastly, we demonstrated that inhibiting QC can attenuate cell migration by lipopolysaccharide. These results strongly suggest that QC-catalysed N-terminal pGlu formation of MCPs is required for monocyte migration and provide new insights into the role of QC in the inflammation process. Our results also suggest that QC could be a drug target for some inflammatory disorders.