Lactobacillus fermentum （L. fermentum） is one of seven species in the genus Lactobacillus[1]. With a long history of safe use in fermented food production, Lactobacillus is considered as one of the most beneficial p...Lactobacillus fermentum （L. fermentum） is one of seven species in the genus Lactobacillus[1]. With a long history of safe use in fermented food production, Lactobacillus is considered as one of the most beneficial probiotics[23]. The most well-known potential health benefit is improving digestion and immune function[4.s]. Other beneficial functions of Lactobacillus strains include managing lactose intoleranceIs], lowering cholesterol and blood pressureIs], reducing inflammation[~], and prevention of cancerIs＇7]. L. fermentum is usually found during malt whisky fermentation]8]. L. fermentum CP34 was found to have the significant effect of decreasing the serum antigen-specific IgE levels compared to a control group[9].展开更多
Agrobacterium radiobacter MTCC 8161 completely decolorized the Crystal Violet with 8 hr （10 mg/L） at static anoxic conditions. The decreased decolorization capability by A. radiobacter was observed, when the Crystal...Agrobacterium radiobacter MTCC 8161 completely decolorized the Crystal Violet with 8 hr （10 mg/L） at static anoxic conditions. The decreased decolorization capability by A. radiobacter was observed, when the Crystal Violet concentration was increased from 10 to 100 mg/L. Semi-synthetic medium containing 1% yeast extract and 0.1% NH4C1 has shown 100% decolorization of Crystal Violet within 5 hr. A complete degradation of Crystal Violet by A. radiobacter was observed up to 7 cycles of repeated addition （10 rag/L）. When the effect of increasing inoculum concentration on decolorization of Crystal Violet （100 mg/L） was studied, maximum decolorization was observed with 15% inoculum concentration. A significant increase in the activities of laccase （184%） and aminopyrine N-demethylase （300%） in cells obtained after decolorization indicated the involvement of these enzymes in decolorization process. The intermediates formed during the degradation of Crystal Violet were analyzed by gas chromatography and mass spectroscopy （GC/MS）. It was detected the presence of N,N,N＇,N＂-tetramethylpararosarfiline, IN, N-dimethylaminophenyl] [N-methylaminophenyl] benzophenone, N, N-dimethylaminobenzaldehyde, 4-methyl amino phenol and phenol. We proposed the hypothetical metabolic pathway of Crystal Violet biodegradation by A. radiobacter. Phytotoxicity and microbial toxicity study showed that Crystal Violet biodegradation metabolites were less toxic to bacteria （A. radiobacter, P. aurugenosa and A. vinelandii） contributing to soil fertility and for four kinds of plants （Sorghum bicolor, Vigna radiata, Lens culinaris and Triticum aestivum） which are most sensitive, fast growing and commonly used in Indian agriculture.展开更多
Na_(v)1.7 is considered a promising target for developing next-generation analgesic drugs,given its critical role in human pain pathologies.Although most reported inhibitors with strong in vitro activity and high sele...Na_(v)1.7 is considered a promising target for developing next-generation analgesic drugs,given its critical role in human pain pathologies.Although most reported inhibitors with strong in vitro activity and high selectivity share the aryl sulfonamide scaffold,they failed to demonstrate marked clinical efficacy.Therefore,exploring new Na_(v)1.7-selective antagonists is quite urgent to the development of next-generation analgesic drugs.Here,we report a highly effective 1H-indole-3-propionamide inhibitor,WN2,identified through an integrated drug discovery strategy.Notably,the structure of WN2 is quite different from previously reported aryl sulfonamide inhibitors.Molecular dynamics simulations and experimental findings reveal that the R configuration of WN2(WN2-R)is the preferred form(IC_(50)=24.7±9.4 nM)within the VSDIV pocket of Na_(v)1.7.WN2-R exhibits impressive analgesic effects in acute and chronic inflammatory pain,as well as neuropathic pain models in mice.Additionally,it displays favorable subtype selectivity and positive drug safety in acute toxicity studies.Pharmacokinetic studies indicate that WN2-R has high bioavailability(F=20.29%),highlighting its considerable potential for drug development.Our study establishes WN2-R as a novel Na_(v)1.7-selective inhibitor with a unique structural scaffold,offering a promising candidate for the next generation of analgesic drugs.展开更多
基金supported by the National Scienceand technology support program(2012BAK01B04)
文摘Lactobacillus fermentum （L. fermentum） is one of seven species in the genus Lactobacillus[1]. With a long history of safe use in fermented food production, Lactobacillus is considered as one of the most beneficial probiotics[23]. The most well-known potential health benefit is improving digestion and immune function[4.s]. Other beneficial functions of Lactobacillus strains include managing lactose intoleranceIs], lowering cholesterol and blood pressureIs], reducing inflammation[~], and prevention of cancerIs＇7]. L. fermentum is usually found during malt whisky fermentation]8]. L. fermentum CP34 was found to have the significant effect of decreasing the serum antigen-specific IgE levels compared to a control group[9].
文摘Agrobacterium radiobacter MTCC 8161 completely decolorized the Crystal Violet with 8 hr （10 mg/L） at static anoxic conditions. The decreased decolorization capability by A. radiobacter was observed, when the Crystal Violet concentration was increased from 10 to 100 mg/L. Semi-synthetic medium containing 1% yeast extract and 0.1% NH4C1 has shown 100% decolorization of Crystal Violet within 5 hr. A complete degradation of Crystal Violet by A. radiobacter was observed up to 7 cycles of repeated addition （10 rag/L）. When the effect of increasing inoculum concentration on decolorization of Crystal Violet （100 mg/L） was studied, maximum decolorization was observed with 15% inoculum concentration. A significant increase in the activities of laccase （184%） and aminopyrine N-demethylase （300%） in cells obtained after decolorization indicated the involvement of these enzymes in decolorization process. The intermediates formed during the degradation of Crystal Violet were analyzed by gas chromatography and mass spectroscopy （GC/MS）. It was detected the presence of N,N,N＇,N＂-tetramethylpararosarfiline, IN, N-dimethylaminophenyl] [N-methylaminophenyl] benzophenone, N, N-dimethylaminobenzaldehyde, 4-methyl amino phenol and phenol. We proposed the hypothetical metabolic pathway of Crystal Violet biodegradation by A. radiobacter. Phytotoxicity and microbial toxicity study showed that Crystal Violet biodegradation metabolites were less toxic to bacteria （A. radiobacter, P. aurugenosa and A. vinelandii） contributing to soil fertility and for four kinds of plants （Sorghum bicolor, Vigna radiata, Lens culinaris and Triticum aestivum） which are most sensitive, fast growing and commonly used in Indian agriculture.
基金supported in part by the National Natural Science Foundation of China(22220102001,22303081,and 32371322)the China Postdoctoral Science Foundation(2022M722795)the Postdoctoral Fellowship Program of CPSF(GZB20230656).
文摘Na_(v)1.7 is considered a promising target for developing next-generation analgesic drugs,given its critical role in human pain pathologies.Although most reported inhibitors with strong in vitro activity and high selectivity share the aryl sulfonamide scaffold,they failed to demonstrate marked clinical efficacy.Therefore,exploring new Na_(v)1.7-selective antagonists is quite urgent to the development of next-generation analgesic drugs.Here,we report a highly effective 1H-indole-3-propionamide inhibitor,WN2,identified through an integrated drug discovery strategy.Notably,the structure of WN2 is quite different from previously reported aryl sulfonamide inhibitors.Molecular dynamics simulations and experimental findings reveal that the R configuration of WN2(WN2-R)is the preferred form(IC_(50)=24.7±9.4 nM)within the VSDIV pocket of Na_(v)1.7.WN2-R exhibits impressive analgesic effects in acute and chronic inflammatory pain,as well as neuropathic pain models in mice.Additionally,it displays favorable subtype selectivity and positive drug safety in acute toxicity studies.Pharmacokinetic studies indicate that WN2-R has high bioavailability(F=20.29%),highlighting its considerable potential for drug development.Our study establishes WN2-R as a novel Na_(v)1.7-selective inhibitor with a unique structural scaffold,offering a promising candidate for the next generation of analgesic drugs.
