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1.
J Org Chem ; 84(14): 9087-9092, 2019 07 19.
Article in English | MEDLINE | ID: mdl-31273973

ABSTRACT

Sekgranaticin (1), a novel hybrid polyketide with a complex 6/6/6/6/6/6/6 7-ring system, was isolated together with granaticins A (2) and B (3) and methyl granaticinate (4) from the culture broth of Streptomyces sp. 166#. Its structure was elucidated by spectroscopic analysis. The absolute configuration was determined on the basis of the calculated 13C NMR and electronic circular dichroism data. Compounds 1-4 exhibited potent cytotoxicity against cancer cell lines MCF-7, A549, P6C, and HCT-116 with IC50 values of 0.02-6.77 µM. The biosynthetic pathway of sekgranaticin (1) was proposed.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antineoplastic Agents/pharmacology , Polyketides/chemistry , Streptomyces/chemistry , Anti-Bacterial Agents/chemistry , Antineoplastic Agents/chemistry , Cell Line, Tumor , Humans , Molecular Structure , Naphthoquinones/chemistry , Streptomyces/classification
2.
J Enzyme Inhib Med Chem ; 32(1): 624-631, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28260395

ABSTRACT

Fibrotic diseases have become a major cause of death in the developed world. AdipoR1 agonists are potent inhibitors of fibrotic responses. Here, we focused on the in silico identification of novel AdipoR1 peptide agonists. A homology model was constructed to predict the 3D structure of AdipoR1. By docking to known active peptides, the putative active site of the model was further explored. A virtual screening study was then carried out with a set of manually designed peptides using molecular docking. Peptides with high docking scores were then evaluated for their anti-fibrotic properties. The data indicated that the novel peptide Pep70 significantly inhibited the proliferation of hepatic stellate cells (HSC) and NIH-3T3 cells (18.33% and 27.80%) and resulted in favouring cell-cycle arrest through increasing the accumulation of cells in the G0/G1 phase by 17.08% and 15.86%, thereby reducing the cell population in the G2/M phase by 11.25% and 15.95%, respectively. Additionally, Pep70 exhibited the most marked suppression on the expression of α-smooth muscle actin (α-SMA), collagen type I alpha1 (COL1A1) and TGF-ß1. Therefore, the peptide Pep70 was ultimately identified as an inhibitor of fibrotic responses and as a potential AdipoR1 agonist.


Subject(s)
Oligopeptides/chemistry , Peptides/pharmacology , Receptors, Adiponectin/agonists , Amino Acid Sequence , Animals , Binding Sites/drug effects , Cell Proliferation/drug effects , Crystallography, X-Ray , Mice , Models, Molecular , Molecular Docking Simulation , NIH 3T3 Cells , Oligopeptides/genetics , Peptides/chemical synthesis , Peptides/chemistry , Rats , Sequence Homology, Amino Acid , Transforming Growth Factor beta1/agonists , Transforming Growth Factor beta1/metabolism
3.
Mar Drugs ; 13(8): 5201-18, 2015 Aug 18.
Article in English | MEDLINE | ID: mdl-26295240

ABSTRACT

Hepatic fibrosis is an effusive wound healing process, characterized by an excessive deposition of extracellular matrix (ECM), as the consequence of chronic liver injury of any etiology. Current therapeutic repertoire for hepatic fibrosis is limited to withdrawal of the noxious agent, which is not always feasible. Hence, in this article, the antifibrotic effects and possible mechanisms of r-sHSA, a recombinant protein with hepatoprotection potential, were investigated. Using NIH/3T3 (mouse embro-fibroblast cell line), skin fibroblasts (human skin fibroblasts, SFBs) and HSC-T6 (rat hepatic stellate cell line), the in vitro effect of r-sHSA was evaluated by measuring the expression levels of alpha-1 Type I collagen (Col1A1) and α-smooth muscle actin (α-SMA). It turned out those fibrosis indicators were typically inhibited by r-sHSA, suggesting its capacity in HSCs inactivation. The antifibrotic activity of r-sHSA was further investigated in vivo on CCl4-induced hepatic fibrosis, in view of significant improvement of the biochemical and histological indicators. More specifically, CCl4-intoxication induced a significant increase in serological biomarkers, e.g., transaminase (AST, ALT), and alkaline phosphatase (ALP), as well as disturbed hepatic antioxidative status; most of the parameters were spontaneously ameliorated to a large extent by withdrawal of CCl4, although the fibrotic lesion was observed histologically. In contrast, r-sHSA treatment markedly eliminated fibrous deposits and restored architecture of the liver in a dose dependent manner, concomitantly with the phenomena of inflammation relief and HSCs deactivation. To sum up, these findings suggest a therapeutic potential for r-sHSA in hepatic fibrosis, though further studies are required.


Subject(s)
Fibrosis/drug therapy , Liver Cirrhosis/drug therapy , Liver/drug effects , Recombinant Proteins/pharmacology , Sharks/metabolism , Actins/metabolism , Animals , Biomarkers/metabolism , Cell Line , Collagen Type I/metabolism , Extracellular Matrix/drug effects , Extracellular Matrix/metabolism , Fibrosis/metabolism , Hepatic Stellate Cells/drug effects , Hepatic Stellate Cells/metabolism , Humans , Inflammation/drug therapy , Inflammation/metabolism , Liver/metabolism , Liver Cirrhosis/metabolism , Mice , NIH 3T3 Cells , Rats
4.
Am J Pathol ; 183(4): 1197-1208, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23906810

ABSTRACT

Members of the early growth response (Egr) gene family of transcription factors have nonredundant biological functions. Although Egr-3 is implicated primarily in neuromuscular development and immunity, its regulation and role in tissue repair and fibrosis has not been studied. We now show that in normal skin fibroblasts, Egr-3 was potently induced by transforming growth factor-ß via canonical Smad3. Moreover, transient Egr-3 overexpression was sufficient to stimulate fibrotic gene expression, whereas deletion of Egr-3 resulted in substantially attenuated transforming growth factor-ß responses. Genome-wide expression profiling in fibroblasts showed that genes associated with tissue remodeling and wound healing were prominently up-regulated by Egr-3. Notably, <5% of fibroblast genes regulated by Egr-1 or Egr-2 were found to be coregulated by Egr-3, revealing substantial functional divergence among these Egr family members. In a mouse model of scleroderma, development of dermal fibrosis was accompanied by accumulation of Egr-3-positive myofibroblasts in the lesional tissue. Moreover, skin biopsy samples from patients with scleroderma showed elevated Egr-3 levels in the dermis, and Egr-3 mRNA levels correlated with the extent of skin involvement. These results provide the first evidence that Egr-3, a functionally distinct member of the Egr family with potent effects on inflammation and immunity, is up-regulated in scleroderma and is necessary and sufficient for profibrotic responses, suggesting important and distinct roles in the pathogenesis of fibrosis.


Subject(s)
Early Growth Response Protein 3/metabolism , Skin/metabolism , Skin/pathology , Transforming Growth Factor beta/pharmacology , Adult , Animals , Disease Models, Animal , Early Growth Response Protein 1/metabolism , Early Growth Response Protein 2/metabolism , Early Growth Response Protein 3/genetics , Female , Fibroblasts/drug effects , Fibroblasts/metabolism , Fibroblasts/pathology , Fibrosis , Gene Expression Profiling , Gene Expression Regulation/drug effects , Humans , Intracellular Space/drug effects , Intracellular Space/metabolism , Male , Mice , Mice, Inbred BALB C , Middle Aged , Scleroderma, Systemic/genetics , Scleroderma, Systemic/pathology , Signal Transduction/drug effects , Signal Transduction/genetics , Skin/drug effects , Smad Proteins/metabolism
5.
Fish Shellfish Immunol ; 40(2): 414-23, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25108086

ABSTRACT

Complement factor I (FI) is a plasma serine proteinase that plays an essential role in the modulation of the complement cascade. In the presence of substrate modulating cofactors (Factor H, C4bp, CR1, etc), FI cleaves the activation products of C3 (i.e. C3b) and C4 (i.e. C4b) to limit complement activity. In this study, the full length cDNA of factor I (CpFI) is isolated from the liver of the whitespotted bamboo shark (Chiloscyllium plagiosum). The CpFI cDNA is 2326 bp in length, encoding a protein of 671 amino acids, which shares 72-80% identity with FI molecules of other sharks, higher than the teleosts (37-40%) and mammals (44-47%). The sequence alignment and comparative analysis indicates the FI proteins are well conserved, with the typical modular architecture and identical active sites throughout vertebrate evolution, suggesting the conserved function. However, the additional sequence present between the leader peptide (LP) and the factor I membrane attack complex (FIMAC) domain in other fishes is also found in CpFI, which consists of two kind of tandem repeats. Phylogenetic analysis suggests that CpFI belongs to the elasmobranch clade, in parallel with the higher vertebrates, to form a sister taxa to teleosts. Expression analysis revealed that CpFI is ubiquitously distributed in a variety of tissues, with the constitutive expression in liver, which might reflect the species-specific distribution patterns of FI. Together with earlier reports, the presence of FI in various sharks might suggest the existence of a well-developed complement regulation mechanism in cartilaginous fish.


Subject(s)
Complement Factor I/genetics , Fish Proteins/genetics , Gene Expression Regulation , Sharks/genetics , Amino Acid Sequence , Animals , Base Sequence , Complement Factor I/chemistry , Complement Factor I/metabolism , DNA, Complementary/genetics , Fish Proteins/chemistry , Fish Proteins/metabolism , Gene Expression Profiling , Male , Molecular Sequence Data , Organ Specificity , Phylogeny , Polymerase Chain Reaction/veterinary , Sequence Alignment/veterinary , Sharks/metabolism
6.
Fish Shellfish Immunol ; 35(6): 1993-2000, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24076167

ABSTRACT

Complement-mediated cytolysis is the important effect of immune response, which results from the assembly of terminal complement components (C5b-9). Among them, α subunit of C8 (C8α) is the first protein that traverses the lipid bilayer, and then initiates the recruitment of C9 molecules to form pore on target membranes. In this article, a full-length cDNA of C8α (CpC8α) is identified from the whitespotted bamboo shark (Chiloscyllium plagiosum) by RACE. The CpC8α cDNA is 2183 bp in length, encoding a protein of 591 amino acids. The deduced CpC8α exhibits 89%, 49% and 44% identity with nurse shark, frog and human orthologs, respectively. Sequence alignment indicates that the C8α is well conserved during the evolution process from sharks to mammals, with the same modular architecture as well as the identical cysteine composition in the mature protein. Phylogenetic analysis places CpC8α and nurse shark C8α in cartilaginous fish clade, in parallel with the teleost taxa, to form the C8α cluster with higher vertebrates. Hydrophobicity analysis also indicates a similar hydrophobicity of CpC8α to mammals. Finally, expression analysis revealed CpC8α transcripts were constitutively highly expressed in shark liver, with much less expression in other tissues. The well conserved structure and properties suggests an analogous function of CpC8α to mammalian C8α, though it remains to be confirmed by further study.


Subject(s)
Complement C8/genetics , Fish Proteins/genetics , Sharks/genetics , Sharks/immunology , Amino Acid Sequence , Animals , Base Sequence , China , Cloning, Molecular , Complement C8/chemistry , Complement C8/metabolism , DNA, Complementary/genetics , DNA, Complementary/metabolism , Fish Proteins/chemistry , Fish Proteins/metabolism , Male , Molecular Sequence Data , Phylogeny , RNA, Messenger/genetics , RNA, Messenger/metabolism , Real-Time Polymerase Chain Reaction , Sequence Alignment
7.
Fish Shellfish Immunol ; 35(2): 599-606, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23684808

ABSTRACT

Complement system is known as highly sophisticated immune defense mechanism for antigen recognition as well as effector functions. Activation of the terminal pathway of the complement system leads to the assembly of terminal complement complexes (C5b-9), which induces the characteristic complement-mediated cytolysis. The lytic activity of shark complement involves functional analogues of mammalian C8 and C9. In this article, a full-length cDNA of C9 (CpC9) is identified from cartilaginous species, the whitespotted bambooshark, Chiloscyllium plagiosum by RACE. The CpC9 cDNA is 2263 bp in length, encoding a protein of 603 amino acids, which shares 42% and 43% identity with human and Xenopus C9 respectively. Through sequence alignment and comparative analysis, the CpC9 protein was found well conserved, with the typical modular architecture in TCCs and nearly unanimous cysteine composition from fish to mammal. Phylogenetic analysis places it in a clade with C9 orthologs in higher vertebrate and as a sister taxa to the Xenopus. Expression analysis revealed that CpC9 is constitutively highly expressed in shark liver, with much less or even undetectable expression in other tissues; demonstrating liver is the primary tissue for C9synthesis. To sum up, the structural conservation and distinctive phylogenetics might indicate the potentially vital role of CpC9 in shark immune response, though it remains to be confirmed by further study.


Subject(s)
Complement C9/genetics , Fish Proteins/genetics , Sharks/genetics , Amino Acid Sequence , Animals , Base Sequence , Cloning, Molecular , Complement C9/chemistry , Complement C9/metabolism , DNA, Complementary/genetics , DNA, Complementary/metabolism , Fish Proteins/chemistry , Fish Proteins/metabolism , Gene Expression Profiling , Molecular Sequence Data , Organ Specificity , Phylogeny , Polymerase Chain Reaction , RNA, Messenger/genetics , RNA, Messenger/metabolism , Sequence Alignment , Sharks/metabolism
8.
Meat Sci ; 191: 108847, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35594692

ABSTRACT

To explore the effects and underlying mechanism of vitamin A on beef marbling fat development, angus steers were injected vitamin A at birth and 1 month of age and in vitro experiments were performed to investigate the effects of retinoic acid (RA) on angiogenesis and adipogenesis of intramuscular stromal vascular (SVF) cells. Results showed that vitamin A administration increased the intramuscular PDGFRα+ adipose progenitors, improved adipogenic potential of intramuscular SVF cells and dramatically upregulated VEGFA. At slaughter, vitamin A increased intramuscular triacylglycerols by 45% without affecting overall fatness. In a 3D culture system, RA promoted capillary sprout development and promoted the subsequent adipogenesis of intramuscular SVF cells by activating VEGFA/VEGFR2 signaling. However, during terminal adipogenesis, RA downregulated PPARγ, C/EBPα and inhibited lipid accumulation. In conclusion, vitamin A/RA upregulate VEGFA and stimulate intramuscular vascular capillary development, which increases intramuscular adipose progenitors and contributes to adipocyte formation. When administrated at neonatal stage, vitamin A promotes beef marbling development without affecting overall fatness.


Subject(s)
Muscle, Skeletal , Vitamin A , Adipocytes , Adipogenesis/physiology , Adipose Tissue , Animals , Cattle , Tretinoin , Vitamin A/pharmacology
9.
Fish Shellfish Immunol ; 30(4-5): 1170-7, 2011.
Article in English | MEDLINE | ID: mdl-21382499

ABSTRACT

Sharks are a type of fish with a full cartilaginous skeleton and have big livers. To better understand liver regeneration in sharks and screening for the important genes participated in disease-defense, in this study, a cDNA library of regenerated liver tissues of shark, Chiloscyllium plagiosum, was constructed. A total of 2103 expressed sequence tags (ESTs), which represents 997 unique genes, were sequenced. Among these genes, 434 (43.53%) of them showed significant similarity (E-values < 10⁻5) to the sequences in NCBI Nt database, 685 (68.71%) of these unique genes showed significant similarity (E-values < 10⁻5) to the sequences in NCBI Nr database, and 662 (66.40%) of these unique genes showed significant similarity (E-values < 10⁻5) to the Swiss-Prot database. Preliminary analysis of unique genes according to COG database showed that unigenes were further grouped into 21 functional categories including inorganic ion transport and metabolism, energy production and conversion, posttranslational modification, protein turnover and chaperones, general function prediction only, translation, and ribosomal structure and biogenesis. Several possible candidate genes involved in liver regeneration were selected to analyze their expression with relative quantification real-time PCR. This study may contribute to our better understanding of the molecular mechanism of regeneration in shark liver. Furthermore, the EST cataloguing and profiling of shark will be also benefited to the functional genomic research in this marine species.


Subject(s)
Liver Regeneration/physiology , Sharks/genetics , Animals , Base Sequence , Cluster Analysis , DNA/chemistry , DNA/genetics , Expressed Sequence Tags , Gene Library , Molecular Sequence Annotation , Molecular Sequence Data , Polymerase Chain Reaction
10.
Arch Environ Contam Toxicol ; 59(1): 129-36, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20044747

ABSTRACT

In the present study, the thermotaxis model was used to evaluate the effects of metal exposure at different concentrations on associative learning behavior in nematodes. The examined nematodes were cultured at 25 or 17 degrees C, and then shifted to 20 degrees C condition. Based on the ability of nematodes to trace the temperature of 20 degrees C, exposure to 10 microM of all examined metals and 2.5 microM Pb and Hg caused significant decrease of associative learning behavior at time intervals of 5 and 18 h; however, exposure to 2.5 microM Cu, Zn, and Ag did not influence associative learning behavior. Moreover, exposure to 2.5 and 10 microM of examined metals did not influence body bend and thermotaxis to cultivation temperature, whereas exposure to 50 microM of examined metals caused significant reduction of body bend and thermotaxis to cultivation temperature. Furthermore, Pb and Hg were the more toxic among the examined metals, with severe toxicity on associative learning behavior, thermotaxis, and locomotion behavior in nematodes.


Subject(s)
Behavior, Animal/drug effects , Caenorhabditis elegans/drug effects , Metals/toxicity , Animals , Association Learning/drug effects , Copper/toxicity , Dose-Response Relationship, Drug , Lead/toxicity , Locomotion/drug effects , Mercury/toxicity , Silver/toxicity , Temperature , Toxicity Tests , Zinc/toxicity
11.
Wei Sheng Wu Xue Bao ; 50(10): 1385-91, 2010 Oct.
Article in Zh | MEDLINE | ID: mdl-21141475

ABSTRACT

OBJECTIVE: To identify Aspergillus awamori strain F12 isolated from rhizospheric soil of Rhizophora stylosa Griff and to characterize antibacterial compounds from the ethyl acetate extracts of its fermentation broth. METHODS: Strain F12 was identified based on its morphological characters and internal transcribed spacer (ITS) sequence. Its secondary metabolites were purified by chromatography, and elucidated by mass spectroscopy, H-NMR, 13C-NMR and physicochemical characters. The antibacterial activities of these compounds were tested against Staphyloccocus aureus and Bacillus subtilis. RESULTS: Strain F12 was identified as Aspergillus awamori. Three compounds, including 1,4-dimethoxybenzene (1), emodin (2) and 3, 6-dibenzylpiperazine-2, 5-dione (3), were purified and elucidated from the ethyl acetate extracts of fermentation broth, among which compound 1 was first reported for the genus of Aspergillus. Compound 2 suppressed the growth of Staphyloccocus aureus and Bacillus subtilis with MIC values of 16 microg/mL and 32 microg/mL respectively, while the other two compounds have no effects on these bacteria. CONCLUSION: Aspergillus awamori strain F12 isolated from rhizospheric soil of Rhizophora stylosa Griff can produce 1, 4-dimethoxybenzene and emodin, among which the latter can suppress the growth of bacteria apparently.


Subject(s)
Anti-Bacterial Agents/pharmacology , Aspergillus/metabolism , Rhizophoraceae/chemistry , Soil Microbiology , Symbiosis , Anti-Bacterial Agents/isolation & purification , Aspergillus/chemistry , Microbial Sensitivity Tests/methods , Rhizophoraceae/metabolism
12.
Mar Drugs ; 7(2): 258-67, 2009 Jun 22.
Article in English | MEDLINE | ID: mdl-19597584

ABSTRACT

The Active Peptide from Shark Liver (APSL) was expressed in E. coli BL21 cells. The cDNA encoding APSL protein was obtained from shark regenerated hepatic tissue by RT-PCR, then it was cloned in the pET-28a expression vector. The expressed fusion protein was purified by Ni-IDA affinity chromatography. SDS-PAGE and HPLC analysis showed the purity of the purified fusion protein was more than 98%. The recombinant APSL (rAPSL) was tested for its biological activity both in vitro, by its ability to improve the proliferation of SMMC7721 cells, and in vivo, by its significant protective effects against acute hepatic injury induced by CCl(4) and AAP (acetaminophen) in mice. In addition, the rAPSL could decrease the blood glucose concentration of mice with diabetes mellitus induced by alloxan. Paraffin sections of mouse pancreas tissues showed that rAPSL (3 mg/kg) could effectively protect mouse islets from lesions induced by alloxan, which indicated its potential application in theoretical research and industry.


Subject(s)
Gene Expression Regulation , Liver/chemistry , Recombinant Proteins/isolation & purification , Recombinant Proteins/metabolism , Sharks/physiology , Animals , Blood Glucose/drug effects , Cell Line , Cell Proliferation/drug effects , Cloning, Molecular , Diabetes Mellitus, Experimental/pathology , Gene Expression Regulation/drug effects , Hepatocytes/drug effects , Liver/drug effects , Mice , Pancreas/drug effects , Recombinant Proteins/pharmacology
13.
J Environ Sci (China) ; 21(7): 971-9, 2009.
Article in English | MEDLINE | ID: mdl-19862965

ABSTRACT

Apart from the liver disruption, embryotoxicity and genotoxicity, microcystin (MC)-LR also could cause neurotoxicity. Nematode Caenorhabditis elegans was explored as a model to study the neurotoxicity. In the present study, we provided evidence to indicate the neurotoxicity on chemotaxis to NaCl and diacetyl, and thermotaxis from MC-LR exposure to C. elegans. As a result, higher concentrations of MC-LR caused significantly severe defects of chemotaxis to NaCl and diacetyl, and thermotaxis. The neurotoxicity on chemotaxis to NaCl and diacetyl, and thermotaxis from MC-LR exposure might be largely mediated by the damage on the corresponding sensory neurons (ASE, AWA, and AFD) and interneuron AIY The expression levels of che-1 and odr-7 were significantly decreased (P < 0.01) in animals exposed to MC-LR at concentrations lower than 10 microg/L, whereas the expression levels of ttx-1 and ttx-3 could be significantly (P < 0.01) lowered in animals even exposed to 1 microg/L of MC-LR. Moreover, both the chemotaxis to NaCl and diacetyl and the thermotaxis were more significantly reduced in MC-LR exposed mutants of che-1(p674), odr-7(ky4), ttx-1(p767), and ttx-3(ks5) than those in exposed wild-type N2 animals at the same concentrations.


Subject(s)
Caenorhabditis elegans/drug effects , Caenorhabditis elegans/physiology , Chemotaxis/drug effects , Diacetyl/pharmacology , Microcystins/toxicity , Sodium Chloride/pharmacology , Animals , Environmental Pollutants/toxicity , Polymerase Chain Reaction , Sensory Receptor Cells/drug effects , Temperature
14.
Article in English | MEDLINE | ID: mdl-30848195

ABSTRACT

AIM AND OBJECTIVE: Small molecule targeted drugs can effectively reduce the toxicity and side effects of drugs, and improve the efficacy of drugs by their specific antitumor activity. Hence, the development of small molecular targeted drugs for cancer has important significance. This study was undertaken to design and synthesize novel phenazine-chromene hybrid molecules in order to optimize the structure and improve the efficacy of this kind of hybrids. MATERIALS AND METHODS: O-diaminobenzene was used as starting material to synthesize twentyfour heterocyclic compounds designed as hybrid molecules of phenazine and 4H-chromene pharmacophores by facile methods. The structures of the compound were confirmed by 1H NMR, 13C NMR and HRMS. Furthermore, the synthesized compounds were evaluated for in vitro activity against four human cancer cell lines and two non-cancer cell lines by MTT test. RESULTS: Some compounds showed strong cytotoxic activities against HepG2 and A549 cancer lines (IC50 = 5-10 µM). Comparing 2i with 2l, the introduction of hydrophilic groups on the phenazine core could not improve the antiproliferative activity significantly. Except 2d and 3c, compounds owning chlorine substituent on the 4H-chromene pharmacophore seemingly contribute to enhance the compounds' antiproliferative activity. Specially, compound 3c showed highest cytotoxicity against A549 cells with IC50 values of 3.3±0.4 µM. Furthermore, all compounds showed low or no cytotoxicity against HUVEC and L02 non-cancer cells in vitro. CONCLUSION: Compound 3c may be used as potential lead molecule against A549 cancer cells.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Benzopyrans/pharmacology , Biological Products/pharmacology , Phenazines/pharmacology , Antineoplastic Agents, Phytogenic/chemical synthesis , Antineoplastic Agents, Phytogenic/chemistry , Benzopyrans/chemistry , Biological Products/chemical synthesis , Biological Products/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Molecular Structure , Phenazines/chemistry , Structure-Activity Relationship
15.
Neurobiol Learn Mem ; 90(1): 10-8, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18191592

ABSTRACT

Vitamin E (alpha-tocopherol), a lipid-soluble anti-oxidant, prevents the uncontrolled propagation of lipid peroxidation by free radicals. Nevertheless, there is weak or no evidence of a protective effect of previous vitamin E intake on cognitive function in humans. In the present study, we explored the thermosensation model to investigate the possible effects of vitamin E administration on memory behaviors in Caenorhabditis elegans. Administration of 100 and 200microg/mL of vitamin E had no significant effects on the memory for different time intervals, whereas relatively high concentration (400microg/mL) of vitamin E exposure shortened the extinction period of the association paradigm (food at 20 degrees C). Following the UV-irradiation, post-treatment with 200microg/mL of vitamin E not only retrieved the UV-irradiation-induced memory deficits, but also enhanced the memory functions in UV-irradiating animals. Post-treatment with trace vitamin E could also ameliorate the memory deficits in metal (Al or Pb) exposed worms. In addition, pre-treatment with 200microg/mL of vitamin E could effectively prevent the occurrence of memory deficits induced by metal exposure and UV-irradiation. Therefore, the close association may exist between trace dietary vitamin E intake and memory behaviors, and a specific response mechanism may be activated after the administration of vitamin E in stress-exposed animals. Moreover, treatment with 200microg/mL of vitamin E could restore the memory deficits formed in the ncs-1 mutant worms, suggesting that exogenous treatment with trace vitamin E can largely mimic the function of NCS-1 in regulating the memory for thermosensation.


Subject(s)
Aluminum/toxicity , Lead/toxicity , Memory Disorders/drug therapy , Ultraviolet Rays/adverse effects , Vitamin E/pharmacology , Vitamins/pharmacology , Animals , Behavior, Animal/drug effects , Behavior, Animal/radiation effects , Caenorhabditis elegans , Memory/drug effects , Memory/radiation effects , Memory Disorders/chemically induced , Mutation , Neuronal Calcium-Sensor Proteins/genetics , Neuropeptides/genetics , Sensory Thresholds/drug effects , Sensory Thresholds/radiation effects , Temperature
16.
Biomed Environ Sci ; 21(6): 467-73, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19263801

ABSTRACT

OBJECTIVE: Previous work has showed that excess iron accumulation is harmful to reproduction and even promotes death; however, whether the multiple biological toxicity of iron (Fe) exposure could be transferred to progeny remains unknown. The present study used Caenorhabditis elegans to analyze the multiple toxicities of iron exposure and their possible transferable properties. METHODS: Three concentrations of iron sulfate solution (2.5 micromol/L, 75 micromol/L, and 200 micromol/L) were used. The endpoints of lifespan, body size, generation time, brood size, head thrash and body bend frequencies, and chemotaxis plasticity were selected to investigate Fe toxicity and its effect on progeny in Caenorhabditis elegans. RESULTS: The Fe toxicity could cause multiple biological defects in a dose-dependent manner by affecting different endpoints in nematodes. Most of the multiple biological defects and behavior toxicities could be transferred from Fe-exposed Caenorhabditis elegans to their progeny. Compared to the parents, no recovery phenotypes were observed for some of the defects in the progeny, such as body bend frequency and life span. We further summarized the defects caused by Fe exposure into 2 groups according to their transferable properties. CONCLUSION: Our results suggest that Fe exposure could cause multiple biological defects, and most of these severe defects could be transferred from Fe exposed nematodes to their progeny.


Subject(s)
Behavior, Animal/drug effects , Caenorhabditis elegans/drug effects , Caenorhabditis elegans/physiology , Iron/toxicity , Phenotype , Soil Pollutants/toxicity , Animals , Behavior, Animal/physiology , Body Size , Caenorhabditis elegans/genetics , Dose-Response Relationship, Drug , Iron Compounds/toxicity , Life Expectancy , Reproduction , Sulfates/toxicity
17.
Yao Xue Xue Bao ; 43(9): 974-8, 2008 Sep.
Article in Zh | MEDLINE | ID: mdl-19048793

ABSTRACT

Ten compounds were isolated from the leaves of Rhizophora stylosa, one kind of mangrove plants distributed in the tropical and subtropical areas of the world. Their structures were identified as taraxerone (1), taraxerol (2), beta-sitosterol (3), careaborin (4), cis-careaborin (5), beta-daucosterol (6), isovanillic acid (7), protocatechuic acid (8), astilbin (9) and rutin (10), among which compound 9 and 10 were reported in this plant for the first time. Of these compounds, Compound 2 has been confirmed to have the abilities to inhibit the growth of Hela and BGC-823 with IC50 of 73.4 micromol x L(-1) and 73.3 micromol x L(-1), respectively. Compound 5 could inhibit the growth of BGC-823 and MCF-7 with IC50 of 45.9 micromol x L(-1) and 116.0 micromol x L(-1), respectively. Compound 9 and 10 were firstly reported to stimulate the proliferation of mice splenic lymphocytes markedly in a dose-dependent manner.


Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Flavonols/isolation & purification , Oleanolic Acid/analogs & derivatives , Rhizophoraceae/chemistry , Triterpenes/isolation & purification , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Flavonols/chemistry , Flavonols/pharmacology , Humans , Inhibitory Concentration 50 , Lymphocytes/cytology , Mice , Molecular Structure , Oleanolic Acid/chemistry , Oleanolic Acid/isolation & purification , Oleanolic Acid/pharmacology , Plant Leaves/chemistry , Rutin/chemistry , Rutin/isolation & purification , Rutin/pharmacology , Spleen/cytology , Triterpenes/chemistry , Triterpenes/pharmacology
18.
PLoS One ; 13(6): e0199572, 2018.
Article in English | MEDLINE | ID: mdl-29949643

ABSTRACT

Based on the feature of high-altitude permafrost topography and the diverse microbial ecological communities of the Qinghai-Tibetan Plateau, soil samples from thirteen different collection points around Qinghai lake were collected to screen for extremophilic strains with the ability to degrade phenol, and one bacterial strain recorded as TIBETAN4 that showed effective biodegradation of phenol was isolated and identified. TIBETAN4 was closely related to Kocuria based on its observed morphological, molecular and biochemical characteristics. TIBETAN4 grew well in the LB medium at pH 7-9 and 0-4% NaCl showing alkalophilicity and halophilism. The isolate could also tolerate up to 12.5 mM phenol and could degrade 5 mM phenol within 3 days. It maintained a high phenol degradation rate at pH 7-9 and 0-3% NaCl in MSM with 5 mM phenol added as the sole carbon source. Moreover, TIBETAN4 could maintain efficient phenol degradation activity in MSM supplemented with both phenol and glucose and complex water environments, including co-culture Penicillium strains or selection of non-sterilized natural lake water as a culture. It was found that TIBETAN4 showed enzymatic activity of phenol hydroxylase and catechol 1,2-dioxygenase after induction by phenol and the corresponding genes of the two enzymes were detected in the genome of the isolate, while catechol 2,3-dioxygenase or its gene was not, which means there could be a degradation pathway of phenol through the ortho-pathway. The Q-PCR results showed that the transcripts of both the phenol hydroxylase gene and catechol 1,2-dioxygenase gene were up-regulated under the stimulation of phenol, demonstrating again that the strain degraded phenol via ortho-degradation pathway.


Subject(s)
Micrococcaceae/isolation & purification , Micrococcaceae/metabolism , Phenol/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Cell Culture Techniques , China , Enzymes/genetics , Enzymes/metabolism , Extremophiles , Hydrogen-Ion Concentration , Lakes/microbiology , Micrococcaceae/growth & development , Penicillium , Sodium Chloride , Soil Microbiology
19.
Chin J Nat Med ; 16(5): 358-365, 2018 May.
Article in English | MEDLINE | ID: mdl-29860997

ABSTRACT

One new sorbicillin derivative, 2-deoxy-sohirnone C (1), one new diketopiperazine alkaloid, 5S-hydroxynorvaline-S-Ile (2), and two naturally occurring diketopiperazines, 3S-hydroxylcyclo(S-Pro-S-Phe) (3) and cyclo(S-Phe-S-Gln) (4), together with three known compounds were isolated from the Chinese mangrove endophytic fungus Penicillium sp. GD6. Their structures were determined on the basis of extensive spectroscopic analyses and by comparison with literature data. The absolute configuration of 3-hydroxyl moiety in 3 was determined by Mosher's method, while the absolute stereochemistry of 2 and 4 was established by comparison with the CD spectra of natural and synthesized diketopiperazines. Compound 1 showed moderate antibacterial activity against Methicillin-resistant Staphylococcus aureus with a MIC value of 80 µg·mL-1.


Subject(s)
Anti-Bacterial Agents/pharmacology , Diketopiperazines/chemistry , Methicillin-Resistant Staphylococcus aureus/drug effects , Penicillium/chemistry , Resorcinols/chemistry , Resorcinols/pharmacology , Rhizophoraceae/microbiology , Alkaloids/chemistry , Alkaloids/isolation & purification , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , China , Circular Dichroism , Diketopiperazines/isolation & purification , Microbial Sensitivity Tests , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Resorcinols/isolation & purification , Wetlands
20.
PLoS One ; 12(5): e0178425, 2017.
Article in English | MEDLINE | ID: mdl-28542542

ABSTRACT

In this study, we designed a microcosm experiment to explore the composition of the bacterial community in the rhizosphere of maize and bulk soil by sequencing the V3-V4 region of the 16S rRNA gene on the Illumina system. 978-1239 OTUs (cut off level of 3%) were found in rhizosphere and bulk soil samples. Rhizosphere shared features with the bulk soil, such as predominance of Acidobacteria, Proteobacteria, Actinobacteria, Bacteroidetes, Chloroflexi, Firmicutes, Gemmatimonadetes and TM7. At genus level, many of the dominant rhizosphere genera (Chitinophaga, Nitrospira, Flavobacterium, etc.) displayed different patterns of temporal changes in the rhizosphere as opposed to the bulk soil, showing rhizosphere has more impact on soil microorganisms. Besides, we found that significant growth-related dynamic changes in bacterial community structure were mainly associated with phylum Bacteroidetes, Proteobacteria and Actinobacteria (mainly genera Burkholderia, Flavisolibacter and Pseudomonas), indicating that different growth stages affected the bacterial community composition in maize soil. Furthermore, some unique genera in especial Plant-Growth Promoting Rhizobacteria (PGPR) such as Nonomuraea, Thiobacillus and Bradyrhizobium etc., which were beneficial for the plant growth appeared to be more abundant in the rhizosphere than bulk soil, indicating that the selectivity of root to rhizosphere microbial is an important mechanism leading to the differences in the bacteria community structure between rhizosphere and bulk soil.


Subject(s)
Bacteria/genetics , Plant Roots/microbiology , Zea mays/microbiology , RNA, Ribosomal, 16S/genetics , Rhizosphere , Sequence Analysis, DNA/methods , Soil , Soil Microbiology
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