The interaction of the anticancer drug hypocrellin B (HB) or the mono-cysteine substituted hypocrellin B (MCHB) and calf thymus deoxyribonucleic acid (CT-DNA) has been investigated using spectral methods. The results ...The interaction of the anticancer drug hypocrellin B (HB) or the mono-cysteine substituted hypocrellin B (MCHB) and calf thymus deoxyribonucleic acid (CT-DNA) has been investigated using spectral methods. The results of UV-visible spectra show that the HB and MCHB could intercalate into the base-stacking domain of the CT-DNA double helix. The studies of fluorescence spectra and circular dichroism(CD) spectra also support the interacalation mechanism.展开更多
Hypocrellin A( HA), a photosensitive perylenequinone compound of Hypocrella bambusae, inhibited the proliferation of several tumor cell lines. Human cervical cancer cells, HeLa ceils, were used as a model to elucida...Hypocrellin A( HA), a photosensitive perylenequinone compound of Hypocrella bambusae, inhibited the proliferation of several tumor cell lines. Human cervical cancer cells, HeLa ceils, were used as a model to elucidate the molecular mechanisms of HA-induced tumor cell death. The results show that HA can induce the oligonucleosomal fragmentation of DNA in HeLa cells and also can increase the expression of apoptosis inducer Bax mRNA and that it decreases the expression of apoptosis suppressor, Bcl-2 mRNA, in mitochondria. It can be concluded from the data that HA-induced apoptosis is related to the balance between Bcl-2 and Bax gene expressions.展开更多
A new hypocrellin B (HB) derivative bearing a bispyrrolecarboxamide-containing side chain was synthesized, which presents improved absorptivity in phototherapeufic window than HB and affinity feature towards dsDNA.
In this paper, the singlet and triplet state electron transfer processes between hypocrellin A(HA) and aromatic amines in solvents of various polarity have been studied by fluorescence and time-resolved transient abso...In this paper, the singlet and triplet state electron transfer processes between hypocrellin A(HA) and aromatic amines in solvents of various polarity have been studied by fluorescence and time-resolved transient absorption spectra. The results show,in.polar solvent, the quenching of HA fluorescence by aromatic amines results in Stern-Volmer plot, the investigation of transient absorption indicated that triplet-state electron transfer process from 3HA to the ground-state of amines occured, and the wines of the singlet and triplet state electron transfer rate constant were calculated, however in weak polar solvent, only the triplet-triplet absorption of HA was observed.展开更多
The fungus Shiraia bambusicola GZ19 M1 is biotechnologically important due to its ability to biosynthesis the pigment hypocrellins.Results showed that ethyl methane sulfonate( EMS) was effective mutagenic agent for st...The fungus Shiraia bambusicola GZ19 M1 is biotechnologically important due to its ability to biosynthesis the pigment hypocrellins.Results showed that ethyl methane sulfonate( EMS) was effective mutagenic agent for strain and potentially produced large numbers of random mutations broadly and uniformly over the whole genome to generate unique strains. Wild-type cultures of S. bambusicola GZ19 were subjected to EMS( 80 mM) induction targeted at approximately 20% spores' survival. When surviving spores were selected in sufficient numbers and cultured on PDA medium for 7 d at 26℃,five novel mutagenized S. bambusicola strains were obtained. A mutant GZ19 M1 that exhibited an activity of more than two times over the wild strain was obtained. Also,batch experiments were carried out to achieve the suitable conditions for hypocrellin. Glucose and rice extract were the most favorable carbon and nitrogen sources for hypocrellin production by submerged culture of S. bambusicola GZ19 M1,and initial glucose and rice extract concentrations were at 35 and 250 g/L,respectively. The optimal surfactant were found to be 0. 008 V/V Tween 80,it was added into cultivation medium at 24 h. Hypocrellin concentration reached 498. 89 mg/L under optimal nutritional conditions,an increment of about 8. 70 times of hypocrellins production was observed compared with that of in non-optimized medium by the wild strain.展开更多
Photodynamic therapy(PDT)has been a routine treatment of tumors and some microvascular diseases,but clinically available photosensitizers are still scarce.Among all kinds of photo-sensitizers,hypocellins possess the m...Photodynamic therapy(PDT)has been a routine treatment of tumors and some microvascular diseases,but clinically available photosensitizers are still scarce.Among all kinds of photo-sensitizers,hypocellins possess the most characteristics of ideal photosensitizers,such as,high photo-activity but low dark toxicity,fast clearance from tssues.This review is focused on two main topics,drug-delivery problem of hypocrellins and how the environment-sensitive fluorescence of bypecrellins was used for recognition of various biomolecules.Drug-delivery of hypocrellins was mainly achieved in two strategies一preparing the drugdelivery vehicles and finding quantitatively amphiphilic derivatives.Hypocrellin fAuorescence originated from the intramolecular proton transfer is very distinct from other kinds of photosensitizers.Recently,it was proved that quan-titative hypocrellin ftuorescence could not only reoognize various biomolecules,including proteins,polysaocharides and lipids,but also distinguish the specific binding from nonspedifie binding with some kind of biomolecules.Meantime,hypocrellin fluorescence was pH sensitive.It is known that tumor cells or tses have the features of a large amount of lipid,neonatal collagen,over expression of polysaccharides,and lower pH values compared to normal tissues.According to the relative but not absolute specifcity,further studies on quantitative recognition of various biomolecules at a cellular level,may find a new clue to treat tumors by joint usage of photodynamic diagnosis(PDD)and PDT.展开更多
OBJECTIVE To prepare hypocrellin B-loaded apoferritin nanoparticles(HB-AFT NPs)for photodynamic therapy on tumor.METHODS HB-AFT NPs were prepared by taking advantage of the reversibleunfolding and refolding character ...OBJECTIVE To prepare hypocrellin B-loaded apoferritin nanoparticles(HB-AFT NPs)for photodynamic therapy on tumor.METHODS HB-AFT NPs were prepared by taking advantage of the reversibleunfolding and refolding character of apoferritin in different pH environments.The photophysical and photobiological properties of hypocrellin B-loaded apoferritin were measured.RESULETS HB molecules were successfully encapsulated within apoferritincavity.HB-AFT-NPs exhibited higher ROS productionthan free HB.Additionally,phototoxicity of HB-AFT NPs to MDA-MB-231 cells was significantly improved as compared to free HB.CONCLUSION Together these results demonstrate that hypocrellin B-loaded apoferritin might be a potential nanoscale photosensitizer.展开更多
A new aminated-perylenequinone derivative 2 was synthesized by the reaction of 1 (hypocrellin B) with 6-aminohexanoic-acid. The structure of 2 was identified by UV-Vis, MS, IR and H-1-NMR. Thc amphiphility spectrum an...A new aminated-perylenequinone derivative 2 was synthesized by the reaction of 1 (hypocrellin B) with 6-aminohexanoic-acid. The structure of 2 was identified by UV-Vis, MS, IR and H-1-NMR. Thc amphiphility spectrum and photochemical properties of 2 were reported.展开更多
OBJECTIVE To investigate the effect of sonodynamic action on biofilm-producing Enterococcus faecalis using hypocrellin B from a natural product Hypocrella bambuase as a sensitizer.METHODS The uptake of hypocrellin B i...OBJECTIVE To investigate the effect of sonodynamic action on biofilm-producing Enterococcus faecalis using hypocrellin B from a natural product Hypocrella bambuase as a sensitizer.METHODS The uptake of hypocrellin B in biofilm-producing Enterococcus faecalis was measured using the fluorescent analysis method.After the combined treatment of hypocrellin B and ultrasound,the growth of biofilm-producing Enterococcus faecalis was measured using the colony counting method,the membrane integrity was detected using a flow cytometric analysis with propidium iodide staining.Chromosomal DNA of bacteria was analysed using apulsed-field gel electrophoresis(PFGE).RESULTS The uptake of hypocrellin B in biofilm-producing Enterocuccus faecalis reached a high peak at the 20 min incubation.After the combined treatment of hypocrellin B,the growth of biofilm-producing Enterocuccus faecalis significantly descreased and membrane integrity was remarkably damaged.However,no remarkable change in bacterial DNA was found.CONCLUSION Sonodynamic action of hypocrellin B had significant killing activity on Enterocuccus faecalis.展开更多
OBJECTIVE To investigate the killing effect of the combined treatment of ultrasound and hypocrellin B,an active component isolated from a natural product Hypocrella bambuase,on Candida albicans.METHODS At first,Candid...OBJECTIVE To investigate the killing effect of the combined treatment of ultrasound and hypocrellin B,an active component isolated from a natural product Hypocrella bambuase,on Candida albicans.METHODS At first,Candida albicans are incubated with hypcrellin B and the uptake of hypocrellin B in Candida albicans was determined using fluorescence intensity analysis.And then the sensitized Candida albicans were exposed to low-intensity of ultrasound.After the combined treatment of ultrasound and hypocellin B,the growth of Candida albicans was evaluated using the colony counting method,and membrane integrity of Candida albicans was also analyzed by a flow cytometry with propidium iodide staining.RESULTS Hypocrellin B was fast absorbed by candida albicans.The growth of candida albicans was more significantly inhibited by the combined treatment of ultrasound and hypocrellin B than the controls(P<0.05).The more marked damages to membrane integrity were found in the combined treatment than the controls(P<0.05).CONCLUSION The combined treatment of ultrasound and hypocrellin B had significant killing effect on Candida albicans,indicating sonodynamic therapy with hypocrellin B from natural product might be a potential approach for combating fungal infections.展开更多
Hypocrellins are major bioactive perylenequinones from Shiraia fruiting bodies and have been developed as efficient photosensitizers for photodynamic therapy.Pseudomonas is the second dominant genus inside Shiraia fru...Hypocrellins are major bioactive perylenequinones from Shiraia fruiting bodies and have been developed as efficient photosensitizers for photodynamic therapy.Pseudomonas is the second dominant genus inside Shiraia fruiting bodies,but with less known actions on the host fungus.In this work,the effects of bacterial volatiles from the Shiraia-associated Pseudomonas on fungal hypocrellin production were investigated.Pseudomonas putida No.24 was the most active to promote significantly accumulation of Shiraia perylenequinones including hypocrellin A(HA),HC,elsinochrome A(EA)and EC.Headspace analysis of the emitted volatiles revealed dimethyl disulfide as one of active compounds to promote fungal hypocrellin production.The bacterial volatiles induced an apoptosis in Shiraia hyphal cell,which was associated with the generation of reactive oxygen species(ROS).ROS generation was proved to mediate the volatile-induced membrane permeability and up-regulation of gene expressions for hypocrellin biosynthesis.In the submerged volatile co-culture,the bacterial volatiles stimulated not only HA content in mycelia,but also HA secretion into the medium,leading to the enhanced HA production to 249.85 mg/L,about 2.07-fold over the control.This is the first report on the regulation of Pseudomonas volatiles on fungal perylenequinone production.These findings could be helpful to understand the roles of bacterial volatiles in fruiting bodies and also provide new elicitation method using bacterial volatiles to stimulate fungal secondary metabolite production.展开更多
Lyme disease(LD)is a tick-transmitted infection caused by Borrelia burgdorferi sensu lato species,which include B.burgdorferi,Borrelia afzelii and Borrelia garinii.The majority of patients with early LD can be cured b...Lyme disease(LD)is a tick-transmitted infection caused by Borrelia burgdorferi sensu lato species,which include B.burgdorferi,Borrelia afzelii and Borrelia garinii.The majority of patients with early LD can be cured by the standard treatment,yet some still suffer from posttreatment LD syndrome.The presence of Borrelia persisters has been proposed as a contributing factor,because they cannot be completely eradicated by the currently used antibiotics for LD.Finding new pharmaceuticals targeting Borrelia persisters is crucial for developing more effective treatments.Here,we first confirmed the existence of persisters in B.garinii and B.afzelii cultures and then conducted a high-throughput screening of a customdrug library against persister-rich stationary-phase B.garinii and B.afzelii cultures.Among 2427 compounds screened,hypocrellin A(HA),anthracycline class of drugs and topical antibiotics along with some other natural compounds were identified to have strong potential for killing persisters of B.garinii and B.afzelii.HA was the most active anti-Borrelia compound,capable of eradicating stationary-phase Borrelia persisters,in particular when combined with doxycycline and/or ceftriaxone.Liposoluble antioxidant vitamin E was found to antagonize the activity of HA,indicating HA’s target is the cell membrane where HA triggers the generation of reactive oxygen species in the presence of light.HA was found to have distinct bactericidal activity against Borrelia species but had poor or no activity against gram-positive and gram-negative bacteria.Identification of the abovementioned drug candidates may help develop more effective therapies for LD.展开更多
1 Introduction Much research work has been done on the mechanism of photo-induced reduction of quinone dyes by electron donors with visible light. Two ways to obtain the net two-electron reduction product QH^- bave be...1 Introduction Much research work has been done on the mechanism of photo-induced reduction of quinone dyes by electron donors with visible light. Two ways to obtain the net two-electron reduction product QH^- bave been proposed. One is the direct two-electron transfer (electron-proton-electron transfer) within the complex and the other is the disproportionatioh of the semiquinone radical QH·formed by one-electron transfer.展开更多
Over recent decades, many studies have reported that hypocrellin A(HA) can eliminate cancer cells with proper irradiation in several cancer cell lines. However, the precise molecular mechanism underlying its anticance...Over recent decades, many studies have reported that hypocrellin A(HA) can eliminate cancer cells with proper irradiation in several cancer cell lines. However, the precise molecular mechanism underlying its anticancer effect has not been fully defined. HA-mediated cytotoxicity and apoptosis in human lung adenocarcinoma A549 cells were evaluated after photodynamic therapy(PDT). A temporal quantitative proteomics approach by isobaric tag for relative and absolute quantitation(iTRAQ) 2 D liquid chromatography with tandem mass spectrometric(LC–MS/MS) was introduced to help clarify molecular cytotoxic mechanisms and identify candidate targets of HA-induced apoptotic cell death. Specific caspaseinhibitors were used to further elucidate the molecular pathway underlying apoptosis in PDT-treated A549 cells. Finally, down-stream apoptosis-related protein was evaluated. Apoptosis induced by HA was associated with cell shrinkage, externalization of cell membrane phosphatidylserine, DNA fragmentation,and mitochondrial disruption, which were preceded by increased intracellular reactive oxygen species(ROS) generations. Further studies showed that PDT treatment with 0.08 mmol/L HA resulted in mitochondrial disruption, pronounced release of cytochrome c, and activation of caspase-3,-9, and-7.Together, HA may be a possible therapeutic agent directed toward mitochondria and a promising photodynamic anticancer candidate for further evaluation.展开更多
Laser Raman spectroscopy provided the direct evidence for microcosmic photodamage in space structure of DNA molecule. When photosensitive damage was made to space structure of calf thymus DNA by hypocrellins A and B, ...Laser Raman spectroscopy provided the direct evidence for microcosmic photodamage in space structure of DNA molecule. When photosensitive damage was made to space structure of calf thymus DNA by hypocrellins A and B, the Raman characteristic frequencies and the intensities of the bands assigned to various groups of the components of DNA (phosphate backbone deoxyribose and four bases) changed at various degrees. There were not only the strand breakage, but also the breakage of some H bonds and disruption of vertical base base stacking interactions. The photosensitive damage of hypocrellin B on DNA was stronger than that of hypocrellin A on DNA.展开更多
文摘The interaction of the anticancer drug hypocrellin B (HB) or the mono-cysteine substituted hypocrellin B (MCHB) and calf thymus deoxyribonucleic acid (CT-DNA) has been investigated using spectral methods. The results of UV-visible spectra show that the HB and MCHB could intercalate into the base-stacking domain of the CT-DNA double helix. The studies of fluorescence spectra and circular dichroism(CD) spectra also support the interacalation mechanism.
基金Supported by the Department of Science and Technology of Jilin Province(No.20020502).
文摘Hypocrellin A( HA), a photosensitive perylenequinone compound of Hypocrella bambusae, inhibited the proliferation of several tumor cell lines. Human cervical cancer cells, HeLa ceils, were used as a model to elucidate the molecular mechanisms of HA-induced tumor cell death. The results show that HA can induce the oligonucleosomal fragmentation of DNA in HeLa cells and also can increase the expression of apoptosis inducer Bax mRNA and that it decreases the expression of apoptosis suppressor, Bcl-2 mRNA, in mitochondria. It can be concluded from the data that HA-induced apoptosis is related to the balance between Bcl-2 and Bax gene expressions.
文摘A new hypocrellin B (HB) derivative bearing a bispyrrolecarboxamide-containing side chain was synthesized, which presents improved absorptivity in phototherapeufic window than HB and affinity feature towards dsDNA.
文摘In this paper, the singlet and triplet state electron transfer processes between hypocrellin A(HA) and aromatic amines in solvents of various polarity have been studied by fluorescence and time-resolved transient absorption spectra. The results show,in.polar solvent, the quenching of HA fluorescence by aromatic amines results in Stern-Volmer plot, the investigation of transient absorption indicated that triplet-state electron transfer process from 3HA to the ground-state of amines occured, and the wines of the singlet and triplet state electron transfer rate constant were calculated, however in weak polar solvent, only the triplet-triplet absorption of HA was observed.
基金Supported by Shandong Provincial Natural Science Foundation(ZR2016BL16&ZR2016CL01)Doctor Foundation of Binzhou University(2016Y17&2016Y02)+2 种基金Project of Shandong Province Higher Educational Science and Technology Program(J17KA120)Research Project of the University-level Teaching Reform of Binzhou University in 2017(BYJYYB201736)Schoolenterprise Co-construction Course Project of Binzhou University in 2017(BYXQGJ201706)
文摘The fungus Shiraia bambusicola GZ19 M1 is biotechnologically important due to its ability to biosynthesis the pigment hypocrellins.Results showed that ethyl methane sulfonate( EMS) was effective mutagenic agent for strain and potentially produced large numbers of random mutations broadly and uniformly over the whole genome to generate unique strains. Wild-type cultures of S. bambusicola GZ19 were subjected to EMS( 80 mM) induction targeted at approximately 20% spores' survival. When surviving spores were selected in sufficient numbers and cultured on PDA medium for 7 d at 26℃,five novel mutagenized S. bambusicola strains were obtained. A mutant GZ19 M1 that exhibited an activity of more than two times over the wild strain was obtained. Also,batch experiments were carried out to achieve the suitable conditions for hypocrellin. Glucose and rice extract were the most favorable carbon and nitrogen sources for hypocrellin production by submerged culture of S. bambusicola GZ19 M1,and initial glucose and rice extract concentrations were at 35 and 250 g/L,respectively. The optimal surfactant were found to be 0. 008 V/V Tween 80,it was added into cultivation medium at 24 h. Hypocrellin concentration reached 498. 89 mg/L under optimal nutritional conditions,an increment of about 8. 70 times of hypocrellins production was observed compared with that of in non-optimized medium by the wild strain.
基金supported by the National Natural Science Foundation of China (Nos.21303223 and 311706144).
文摘Photodynamic therapy(PDT)has been a routine treatment of tumors and some microvascular diseases,but clinically available photosensitizers are still scarce.Among all kinds of photo-sensitizers,hypocellins possess the most characteristics of ideal photosensitizers,such as,high photo-activity but low dark toxicity,fast clearance from tssues.This review is focused on two main topics,drug-delivery problem of hypocrellins and how the environment-sensitive fluorescence of bypecrellins was used for recognition of various biomolecules.Drug-delivery of hypocrellins was mainly achieved in two strategies一preparing the drugdelivery vehicles and finding quantitatively amphiphilic derivatives.Hypocrellin fAuorescence originated from the intramolecular proton transfer is very distinct from other kinds of photosensitizers.Recently,it was proved that quan-titative hypocrellin ftuorescence could not only reoognize various biomolecules,including proteins,polysaocharides and lipids,but also distinguish the specific binding from nonspedifie binding with some kind of biomolecules.Meantime,hypocrellin fluorescence was pH sensitive.It is known that tumor cells or tses have the features of a large amount of lipid,neonatal collagen,over expression of polysaccharides,and lower pH values compared to normal tissues.According to the relative but not absolute specifcity,further studies on quantitative recognition of various biomolecules at a cellular level,may find a new clue to treat tumors by joint usage of photodynamic diagnosis(PDD)and PDT.
基金The project supported by the general grant fund from Hong Kong Research Grant Committee(476912)Health and Medical Research Fund(13120442)Innovation and Technology Fund of Shenzhen(CXZZ20120619150627260)
文摘OBJECTIVE To prepare hypocrellin B-loaded apoferritin nanoparticles(HB-AFT NPs)for photodynamic therapy on tumor.METHODS HB-AFT NPs were prepared by taking advantage of the reversibleunfolding and refolding character of apoferritin in different pH environments.The photophysical and photobiological properties of hypocrellin B-loaded apoferritin were measured.RESULETS HB molecules were successfully encapsulated within apoferritincavity.HB-AFT-NPs exhibited higher ROS productionthan free HB.Additionally,phototoxicity of HB-AFT NPs to MDA-MB-231 cells was significantly improved as compared to free HB.CONCLUSION Together these results demonstrate that hypocrellin B-loaded apoferritin might be a potential nanoscale photosensitizer.
基金the National Natural Science Foundation of China (Project No.39830090 and No.39970871) for their financial support to this resea
文摘A new aminated-perylenequinone derivative 2 was synthesized by the reaction of 1 (hypocrellin B) with 6-aminohexanoic-acid. The structure of 2 was identified by UV-Vis, MS, IR and H-1-NMR. Thc amphiphility spectrum and photochemical properties of 2 were reported.
基金The project supported by the General Research Fund Grant from Hong Kong Research Grant Committee(476912)Health and Medical Research Fund(13120442)
文摘OBJECTIVE To investigate the effect of sonodynamic action on biofilm-producing Enterococcus faecalis using hypocrellin B from a natural product Hypocrella bambuase as a sensitizer.METHODS The uptake of hypocrellin B in biofilm-producing Enterococcus faecalis was measured using the fluorescent analysis method.After the combined treatment of hypocrellin B and ultrasound,the growth of biofilm-producing Enterococcus faecalis was measured using the colony counting method,the membrane integrity was detected using a flow cytometric analysis with propidium iodide staining.Chromosomal DNA of bacteria was analysed using apulsed-field gel electrophoresis(PFGE).RESULTS The uptake of hypocrellin B in biofilm-producing Enterocuccus faecalis reached a high peak at the 20 min incubation.After the combined treatment of hypocrellin B,the growth of biofilm-producing Enterocuccus faecalis significantly descreased and membrane integrity was remarkably damaged.However,no remarkable change in bacterial DNA was found.CONCLUSION Sonodynamic action of hypocrellin B had significant killing activity on Enterocuccus faecalis.
基金The project supported by Health and Medical Research Fund(13120442)the General Research Fund(GRF)Grant from Hong Kong Research Grant Committee(476912)
文摘OBJECTIVE To investigate the killing effect of the combined treatment of ultrasound and hypocrellin B,an active component isolated from a natural product Hypocrella bambuase,on Candida albicans.METHODS At first,Candida albicans are incubated with hypcrellin B and the uptake of hypocrellin B in Candida albicans was determined using fluorescence intensity analysis.And then the sensitized Candida albicans were exposed to low-intensity of ultrasound.After the combined treatment of ultrasound and hypocellin B,the growth of Candida albicans was evaluated using the colony counting method,and membrane integrity of Candida albicans was also analyzed by a flow cytometry with propidium iodide staining.RESULTS Hypocrellin B was fast absorbed by candida albicans.The growth of candida albicans was more significantly inhibited by the combined treatment of ultrasound and hypocrellin B than the controls(P<0.05).The more marked damages to membrane integrity were found in the combined treatment than the controls(P<0.05).CONCLUSION The combined treatment of ultrasound and hypocrellin B had significant killing effect on Candida albicans,indicating sonodynamic therapy with hypocrellin B from natural product might be a potential approach for combating fungal infections.
基金the National Natural Science Foundation of China(No.82073955 and 81773696)the Priority Academic Program Development of the Jiangsu Higher Education Institutes(PAPD).
文摘Hypocrellins are major bioactive perylenequinones from Shiraia fruiting bodies and have been developed as efficient photosensitizers for photodynamic therapy.Pseudomonas is the second dominant genus inside Shiraia fruiting bodies,but with less known actions on the host fungus.In this work,the effects of bacterial volatiles from the Shiraia-associated Pseudomonas on fungal hypocrellin production were investigated.Pseudomonas putida No.24 was the most active to promote significantly accumulation of Shiraia perylenequinones including hypocrellin A(HA),HC,elsinochrome A(EA)and EC.Headspace analysis of the emitted volatiles revealed dimethyl disulfide as one of active compounds to promote fungal hypocrellin production.The bacterial volatiles induced an apoptosis in Shiraia hyphal cell,which was associated with the generation of reactive oxygen species(ROS).ROS generation was proved to mediate the volatile-induced membrane permeability and up-regulation of gene expressions for hypocrellin biosynthesis.In the submerged volatile co-culture,the bacterial volatiles stimulated not only HA content in mycelia,but also HA secretion into the medium,leading to the enhanced HA production to 249.85 mg/L,about 2.07-fold over the control.This is the first report on the regulation of Pseudomonas volatiles on fungal perylenequinone production.These findings could be helpful to understand the roles of bacterial volatiles in fruiting bodies and also provide new elicitation method using bacterial volatiles to stimulate fungal secondary metabolite production.
基金the National Natural Science Foundation of China(no.81902099)the State Key Laboratory of Veterinary Etiological Biology,Lanzhou Veterinary Research Institute,Chinese Academy of Agricultural Sciences(no.SKLVEB2020KFKT005).
文摘Lyme disease(LD)is a tick-transmitted infection caused by Borrelia burgdorferi sensu lato species,which include B.burgdorferi,Borrelia afzelii and Borrelia garinii.The majority of patients with early LD can be cured by the standard treatment,yet some still suffer from posttreatment LD syndrome.The presence of Borrelia persisters has been proposed as a contributing factor,because they cannot be completely eradicated by the currently used antibiotics for LD.Finding new pharmaceuticals targeting Borrelia persisters is crucial for developing more effective treatments.Here,we first confirmed the existence of persisters in B.garinii and B.afzelii cultures and then conducted a high-throughput screening of a customdrug library against persister-rich stationary-phase B.garinii and B.afzelii cultures.Among 2427 compounds screened,hypocrellin A(HA),anthracycline class of drugs and topical antibiotics along with some other natural compounds were identified to have strong potential for killing persisters of B.garinii and B.afzelii.HA was the most active anti-Borrelia compound,capable of eradicating stationary-phase Borrelia persisters,in particular when combined with doxycycline and/or ceftriaxone.Liposoluble antioxidant vitamin E was found to antagonize the activity of HA,indicating HA’s target is the cell membrane where HA triggers the generation of reactive oxygen species in the presence of light.HA was found to have distinct bactericidal activity against Borrelia species but had poor or no activity against gram-positive and gram-negative bacteria.Identification of the abovementioned drug candidates may help develop more effective therapies for LD.
基金Project supported by the National Natural Science Foundation of China
文摘1 Introduction Much research work has been done on the mechanism of photo-induced reduction of quinone dyes by electron donors with visible light. Two ways to obtain the net two-electron reduction product QH^- bave been proposed. One is the direct two-electron transfer (electron-proton-electron transfer) within the complex and the other is the disproportionatioh of the semiquinone radical QH·formed by one-electron transfer.
基金supported by the National Natural Science Foundation of China(Project No.81673214)The National Key Technology Research and National Key Technology Research and Development Program of the Ministry of Science and Technology of the People's Republic of China(Project No.2012BAD36B0502)the Priority Academic Program Development of Jiangsu Higher Educational Institutions(China)
文摘Over recent decades, many studies have reported that hypocrellin A(HA) can eliminate cancer cells with proper irradiation in several cancer cell lines. However, the precise molecular mechanism underlying its anticancer effect has not been fully defined. HA-mediated cytotoxicity and apoptosis in human lung adenocarcinoma A549 cells were evaluated after photodynamic therapy(PDT). A temporal quantitative proteomics approach by isobaric tag for relative and absolute quantitation(iTRAQ) 2 D liquid chromatography with tandem mass spectrometric(LC–MS/MS) was introduced to help clarify molecular cytotoxic mechanisms and identify candidate targets of HA-induced apoptotic cell death. Specific caspaseinhibitors were used to further elucidate the molecular pathway underlying apoptosis in PDT-treated A549 cells. Finally, down-stream apoptosis-related protein was evaluated. Apoptosis induced by HA was associated with cell shrinkage, externalization of cell membrane phosphatidylserine, DNA fragmentation,and mitochondrial disruption, which were preceded by increased intracellular reactive oxygen species(ROS) generations. Further studies showed that PDT treatment with 0.08 mmol/L HA resulted in mitochondrial disruption, pronounced release of cytochrome c, and activation of caspase-3,-9, and-7.Together, HA may be a possible therapeutic agent directed toward mitochondria and a promising photodynamic anticancer candidate for further evaluation.
文摘Laser Raman spectroscopy provided the direct evidence for microcosmic photodamage in space structure of DNA molecule. When photosensitive damage was made to space structure of calf thymus DNA by hypocrellins A and B, the Raman characteristic frequencies and the intensities of the bands assigned to various groups of the components of DNA (phosphate backbone deoxyribose and four bases) changed at various degrees. There were not only the strand breakage, but also the breakage of some H bonds and disruption of vertical base base stacking interactions. The photosensitive damage of hypocrellin B on DNA was stronger than that of hypocrellin A on DNA.