Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 48
Filter
Add more filters










Publication year range
1.
Ecol Evol ; 12(2): e8629, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35222979

ABSTRACT

Ziziphus spinosa (Bunge) H.H. Hu ex F.H. Chen is a woody plant species of the family Rhamnaceae (order Rhamnales) that possesses high nutritional and medicinal value. Predicting the effects of climate change on the distribution of Z. spinosa is of great significance for the investigation, protection, and exploitation of this germplasm resource. For this study, optimized maximum entropy models were employed to predict the distribution patterns and changes of its present (1970-2000) and future (2050s, 2070s, and 2090s) potential suitable regions in China under multiple climate scenarios (SSP1-2.6, SSP2-4.5, SSP3-7.0 & SSP5-8.5). The results revealed that the total area of the present potential suitable region for Z. spinosa is 162.60 × 104 km2, which accounts for 16.94% of China's territory. Within this area, the regions having low, medium, and high suitability were 80.14 × 104 km2, 81.50 × 104 km2, and 0.96 × 104 km2, respectively, with the high suitability regions being distributed primarily in Shanxi, Hebei, and Beijing Provinces. Except for SSP-1-2.6-2070s, SSP-5-8.5-2070s, and SSP-5-8.5-2090s, the suitable areas for Z. spinosa in the future increased to different degrees. Meanwhile, considering the distribution of Z. spinosa during different periods and under different climate scenarios, our study predicted that the low impact areas of Z. spinosa were mainly restricted to Shanxi, Shaanxi, Ningxia, Gansu, Liaoning, Inner Mongolia, and Jilin Provinces. The results of core distributional shifts showed that, except for SSP1-2.6, the center of the potential suitable region of Z. spinosa exhibited a trend of gradually shifting to the northwest.

2.
Plants (Basel) ; 10(10)2021 Oct 14.
Article in English | MEDLINE | ID: mdl-34685993

ABSTRACT

Bletilla striata (Thunb. ex A. Murray) Rchb. f., a species of the perennial herb Orchidaceae, has potent anti-inflammatory and antiviral biological activities. MADS-box transcription factors play critical roles in the various developmental processes of plants. Although this gene family has been extensively investigated in many species, it has not been analyzed for B. striata. In total, 45 MADS-box genes were identified from B. striata in this study, which were classified into five subfamilies (Mδ, MIKC, Mα, Mß, and Mγ). Meanwhile, the highly correlated protein domains, motif compositions, and exon-intron structures of BsMADSs were investigated according to local B. striata databases. Chromosome distribution and synteny analyses revealed that segmental duplication and homologous exchange were the main BsMADSs expansion mechanisms. Further, RT-qPCR analysis revealed that BsMADSs had different expression patterns in response to various stress treatments. Our results provide a potential theoretical basis for further investigation of the functions of MADS genes during the growth of B. striata.

3.
EBioMedicine ; 64: 103227, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33530002

ABSTRACT

BACKGROUND: Urolithin A (URA) is an intestinal microbiota metabolic product from ellagitannin-containing foods with multiple biological activities. However, its role in autoimmune diseases is largely unknown. Here, for first time, we demonstrate the therapeutic effect of URA in an experimental autoimmune encephalomyelitis (EAE) animal model. METHODS: Therapeutic effect was evaluated via an active and passive EAE animal model in vivo. The function of URA on bone marrow-derived dendritic cells (BM-DCs), T cells, and microglia were tested in vitro. FINDINGS: Oral URA (25 mg/kg/d) suppressed disease progression at prevention, induction, and effector phases of preclinical EAE. Histological evaluation showed that significantly fewer inflammatory cells, decreased demyelination, lower numbers of M1-type microglia and activated DCs, as well as reduced infiltrating Th1/Th17 cells were present in the central nervous system (CNS) of the URA-treated group. URA treatment at 25 µM inhibited the activation of BM-DCs in vitro, restrained Th17 cell differentiation in T cell polarization conditions, and in a DC-CD4+ T cell co-culture system. Moreover, we confirmed URA inhibited pathogenicity of Th17 cells in adoptive EAE. Mechanism of URA action was directly targeting Aryl Hydrocarbon Receptor (AhR) and modulating the signaling pathways. INTERPRETATION: Collectively, our study offers new evidence that URA, as a human microbial metabolite, is valuable to use as a prospective therapeutic candidate for autoimmune diseases.


Subject(s)
Coumarins/pharmacology , Encephalomyelitis, Autoimmune, Experimental/etiology , Encephalomyelitis, Autoimmune, Experimental/metabolism , Receptors, Aryl Hydrocarbon/metabolism , Animals , Biomarkers , Coumarins/chemistry , Disease Models, Animal , Disease Susceptibility , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Encephalomyelitis, Autoimmune, Experimental/pathology , Female , Immunohistochemistry , Mice , Models, Molecular , Molecular Targeted Therapy , Receptors, Aryl Hydrocarbon/antagonists & inhibitors , Receptors, Aryl Hydrocarbon/chemistry , Receptors, Aryl Hydrocarbon/genetics , Structure-Activity Relationship
4.
Food Funct ; 11(8): 6875-6888, 2020 Aug 01.
Article in English | MEDLINE | ID: mdl-32686813

ABSTRACT

T helper 17 (Th17) cells that express interleukin-17 (IL-17) play a key role in various inflammatory diseases, such as multiple sclerosis (MS), and its animal model experimental autoimmune encephalomyelitis (EAE). The retinoic acid receptor-related orphan receptors γt (RORγt) have an indispensable effect on the differentiation of this cell type, and are thus considered a valuable target in the treatment of Th17-related disorders. In this study, we found that eriodictyol (EDT), a natural flavonoid abundant in citrus fruits and peanuts, was located directly in the binding pocket of RORγt, and induced a conformational change that resulted in the effective suppression of the receptor's activity, thus offering insight into the transcriptional inhibition of RORγt-dependent genes. Consistent with this, EDT dose-dependently (5-10 µM) blocked murine Th17 differentiation, and markedly reduced IL-17A secretion in vitro. Furthermore, this compound has been found to have novel properties for directly inhibiting Th1 cell development and promoting Treg cell differentiation at high doses (≥10 µM). EDT administration significantly decreased the clinical severity in the EAE model, with inhibited demyelination and reduced inflammatory responses in the periphery and in the central nervous system (CNS). In the adoptive transfer model, EDT also remarkably suppressed the Th17 cell infiltration and pathogenicity. Collectively, our data demonstrated that EDT, as an agent for the pharmacological inhibition of RORγt, has great potential for immunomodulation, and for use in the treatment of Th17-mediated autoimmune disease.


Subject(s)
Cell Differentiation/drug effects , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Flavanones/pharmacology , Interleukin-17/metabolism , Th17 Cells/immunology , Adoptive Transfer , Animals , Cell Differentiation/immunology , Dose-Response Relationship, Immunologic , Encephalomyelitis, Autoimmune, Experimental/immunology , Mice , Nuclear Receptor Subfamily 1, Group F, Member 3/antagonists & inhibitors , Th17 Cells/cytology
5.
Plant Physiol Biochem ; 153: 131-140, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32502715

ABSTRACT

WD40 proteins play crucial roles in response to abiotic stress. By screening the genome sequences of Salvia miltiorrhiza Bunge, 225 SmWD40 genes were identified and divided into 9 subfamilies (I-IX). Physiological, biochemical, gene structure, conserved protein motif and GO annotation analyses were performed on SmWD40 family members. The SmWD40-170 was found in 110 SmWD40 genes that contain drought response elements, SmWD40-170 was one of these genes whose response in terms of expression under drought was significant. The expression of SmWD40-170 was also up-regulated by ABA and H2O2. Through observed the stomatal phenotype of SmWD40-170 transgenic lines, the stomatal closure was abolished under dehydration, ABA and H2O2 treatment in SmWD40-170 knockdown lines. Abscisic acid (ABA), as the key phytohormone, elevates reactive oxygen species (ROS) levels under drought stress. The ABA-ROS interaction mediated the generation of H2O2 and the activation of anion channel in guard cells. The osmolality alteration of guard cells further accelerated the stomatal closure. As a second messenger, nitric oxide (NO) regulated ABA signaling, the NO stimulated protein kinase activity inhibited the K+ influx which result in stomatal closure. These NO-relevant events were essential for ABA-induced stomatal closure. The reduction of NO production was also observed in the guard cells of SmWD40-170 knockdown lines. The abolished of stomatal closure attributed to the SmWD40-170 deficiency induced the reduction of NO content. In general, the SmWD40-170 is a critical drought response gene in SmWD40 gene family and regulates ABA- and H2O2-induced stomatal movement by affecting the synthesis of NO.


Subject(s)
Droughts , Genes, Plant , Plant Stomata/physiology , Salvia miltiorrhiza/physiology , WD40 Repeats , Abscisic Acid/pharmacology , Hydrogen Peroxide/pharmacology , Nitric Oxide , Potassium , Salvia miltiorrhiza/genetics , Stress, Physiological
6.
Psychoneuroendocrinology ; 119: 104767, 2020 09.
Article in English | MEDLINE | ID: mdl-32563935

ABSTRACT

Major depressive disorder (MDD) is a common mental disorder characterized by a persistent feeling of sadness, slow thought, impaired focus and loss of interest but the underlying mechanisms are largely unknown. Dendritic spines play an important role in the formation and maintenance of emotional circuits in the brain. Abnormalities in this process can lead to psychiatric diseases. 7,8-Dihydroxy-4-methylcoumarin (Dhmc), a precursor in the synthesis of derivatives of 4-methyl coumarin, plays an important role in protecting the nervous system from developing diseases and its most distinctive feature is safety. The aim of this study was to investigate whether Dhmc alleviates chronic unpredictable mild stress (CUMS)-induced depression-like behaviors and reverses CUMS-induced alterations in dendritic spines of principal neurons in brain areas of the emotional circuits including the hippocampus, medial prefrontal cortex (mPFC), nucleus accumbens (NAc) and basolateral amygdala (BLA) in male rats. Our results showed that CUMS-induced depression-like behaviors were accompanied by a decrease in spine density in pyramidal neurons of both the hippocampal CA3 area and the mPFC, and an increase in spine density in both the neurons of BLA and the medium spiny neurons (MSNs) of the NAc, as well as a decrease in the levels of the AMPA receptor subunit GluA1 and Kalirin-7 in the hippocampus compared with the control group. Intraperitoneal injection (i.p.) of Dhmc to the CUMS-exposed rats ameliorated CUMS-induced depression-like behaviors and reversed CUMS-mediated alterations in spine density and the levels of both GluA1 and Kalirin-7. Our results show an important role of Dhmc in reversing CUMS-induced depression-like behaviors and CUMS-mediated alterations in spine density.


Subject(s)
Affect/drug effects , Coumarins/therapeutic use , Dendritic Spines/drug effects , Depression/drug therapy , Animals , Behavior, Animal/drug effects , Coumarins/pharmacology , Dendritic Spines/pathology , Dendritic Spines/physiology , Depression/pathology , Depression/psychology , Disease Models, Animal , Male , Nerve Net/drug effects , Nerve Net/pathology , Nerve Net/physiology , Rats , Rats, Sprague-Dawley , Stress, Psychological/drug therapy , Stress, Psychological/pathology , Stress, Psychological/physiopathology , Stress, Psychological/psychology
8.
Gene ; 742: 144603, 2020 Jun 05.
Article in English | MEDLINE | ID: mdl-32198126

ABSTRACT

Adverse environmental conditions, such as salinity, cold, drought, heavy metals, and pathogens affect the yield and quality of Salvia miltiorrhiza, a well-known medicinal plant used for the treatment of cardiovascular and cerebrovascular diseases. Superoxide dismutase (SOD), a key enzyme of antioxidant system in plants, plays a vital role in protecting plants against various biotic and abiotic stresses via scavenging the reactive oxygen species produced by organisms. However, little is known about the SOD gene family in S. miltiorrhiza. In this study, eight SOD genes, including three Cu/Zn-SODs, two Fe-SODs and three Mn-SODs, were identified in the S. miltiorrhiza genome. Their gene structures, promoters, protein features, phylogenetic relationships, and expression profiles were comprehensively investigated. Gene structure analysis implied that most SmSODs have different introns/exons distrbution patterns. Many cis-elements related to different stress responses or plant hormones were found in the promoter of each SmSOD. Expression profile analysis indicated that SmSODs exhibited diverse responses to cold, salt, drought, heavy metal, and plant hormones. Additionally, 31 types of TFs regulating SmSODs were predicted and analyzed. These findings provided valuable information for further researches on the functions and applications of SmSODs in S. miltiorrhiza growth and adaptation to stress.


Subject(s)
Gene Expression Regulation, Plant , Multigene Family/genetics , Plant Proteins/genetics , Salvia miltiorrhiza/genetics , Superoxide Dismutase/genetics , Acclimatization/genetics , Droughts , Exons/genetics , Gene Expression Profiling , Introns/genetics , Phylogeny , Plant Breeding , Plant Proteins/metabolism , Salinity , Salvia miltiorrhiza/enzymology , Stress, Physiological/genetics , Superoxide Dismutase/metabolism , Transcription Factors/metabolism
10.
Front Pharmacol ; 10: 863, 2019.
Article in English | MEDLINE | ID: mdl-31427972

ABSTRACT

Scopoletin, a phenolic coumarin derived from many medical or edible plants, is involved in various pharmacological functions. In the present study, we showed that Scopoletin effectively ameliorated experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), through novel regulatory mechanisms involving inhibition of NF-κB activity in dendritic cells (DCs). Scopoletin treatment significantly improved the severity of the disease and prominently decreased inflammation and demyelination of central nervous system (CNS) in EAE mice. Disease alleviation correlated with the downregulation of major histocompatibility complex (MHC) class II, CD80 and CD86, expressed on DCs of CNS or spleens, and the infiltration and polarization of encephalitogenic Th1/Th17 cells. Consistent with the in vivo data, Scopoletin-treated, bone marrow-derived dendritic cells (BM-DCs) exhibited reduced expression of MHC class II and costimulatory molecules (e.g., CD80 and CD86) and reduced NF-κB phosphorylation. These findings, for the first time, demonstrated the ability of Scopoletin to impair DC activation, downregulating pathogenic Th1/Th17 inflammatory cell responses and, eventually, reducing EAE severity. Our study demonstrates new evidence that natural products derived from medical or edible plants, such as Scopoletin, will be valuable in developing a novel therapeutic agent for MS in the future.

11.
Mol Nutr Food Res ; 63(18): e1801356, 2019 09.
Article in English | MEDLINE | ID: mdl-31313461

ABSTRACT

SCOPE: Multiple sclerosis (MS) is an inflammatory demyelinating autoimmune disorder, with increasing incidence worldwide but unknown etiology. 6-Gingerol (6-GIN), a major dietary compound found in ginger rhizome, has immunomodulatory activity. However, its role in autoimmune diseases, as well as the underlying mechanisms, are unclear. In this study, it is evaluated if 6-GIN can effectively ameliorate the clinical disease severity of experimental autoimmune encephalomyelitis, an animal model of MS. METHODS AND RESULTS: Clinical scores of experimental autoimmune encephalomyelitis (EAE) mice are recorded daily. Inflammation of periphery and neuroinflammation of EAE mice are determined by flow cytometry analysis, ELISA, and histopathological analysis, and results show that 6-GIN significantly inhibits inflammatory cell infiltration from the periphery into the central nervous system and reduces neuroinflammation and demyelination. Flow cytometry analysis, ELISA, and quantitative PCR show that 6-GIN could suppress lipolysaccharide-induced dendritic cell (DC) activation and induce the tolerogenic DCs. Immunoblot analysis reveals that the phosphorylation of nuclear factor-κB and mitogen-activated protein kinase, two critical regulators of inflammatory signaling, are significantly inhibited in 6-GIN-treated DCs. CONCLUSION: The results of this study demonstrate that 6-GIN has significant potential as a novel anti-inflammatory agent for the treatment of autoimmune diseases such as MS via direct modulatory effects on DCs.


Subject(s)
Catechols/pharmacology , Dendritic Cells/drug effects , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Fatty Alcohols/pharmacology , Animals , Cell Differentiation/drug effects , Dendritic Cells/immunology , Dendritic Cells/metabolism , Encephalomyelitis, Autoimmune, Experimental/immunology , Female , Lipopolysaccharides/pharmacology , MAP Kinase Signaling System/drug effects , Mice, Inbred C57BL , NF-kappa B/metabolism , Th17 Cells/cytology , Th17 Cells/drug effects
12.
Front Genet ; 10: 1321, 2019.
Article in English | MEDLINE | ID: mdl-32010187

ABSTRACT

The Asian Buffalo leech, Hirudinaria manillensis, is an aquatic sanguivorous species distributed widely in Southeast Asia. H. manillensis has long been used clinically for bloodletting and other medical purposes. Recent studies have focused on artificial culturing, strain optimization, and the identification and development new drugs based on the anticoagulant effects of H. manillensis bites; however, data regarding its genome remain unclear. This study aimed to determine the genome sequence of an adult Asian Buffalo leech. We generated a draft assembly of 151.8 Mb and a N50 scaffold of 2.28 Mb. Predictions indicated that the assembled genome contained 21,005 protein-coding genes. Up to 17,865 genes were annotated in multiple databases including Gene Ontology. Sixteen anticoagulant proteins with a Hirudin or Antistasin domain were identified. This study is the first to report the whole-genome sequence of the Asian Buffalo leech, an important sanguivorous leech of clinical significance. The quality of the assembly is comparable to those of other annelids. These data will help further the current understanding of the biological mechanisms and genetic characteristics of leeches and serve as a valuable resource for future studies.

13.
Front Immunol ; 9: 1807, 2018.
Article in English | MEDLINE | ID: mdl-30150982

ABSTRACT

Medicinal plants as a rich pool for developing novel small molecule therapeutic medicine have been used for thousands of years. Carnosol as a bioactive diterpene compound originated from Rosmarinus officinalis (Rosemary) and Salvia officinalis, herbs extensively applied in traditional medicine for the treatment of multiple autoimmune diseases (1). In this study, we investigated the therapeutic effects and molecule mechanism of carnosol in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Carnosol treatment significantly alleviated clinical development in the myelin oligodendrocyte glycoprotein (MOG35-55) peptide-induced EAE model, markedly decreased inflammatory cell infiltration into the central nervous system and reduced demyelination. Further, carnosol inhibited Th17 cell differentiation and signal transducer and activator of transcription 3 phosphorylation, and blocked transcription factor NF-κB nuclear translocation. In the passive-EAE model, carnosol treatment also significantly prevented Th17 cell pathogenicity. Moreover, carnosol exerted its therapeutic effects in the chronic stage of EAE, and, remarkably, switched the phenotypes of infiltrated macrophage/microglia. Taken together, our results show that carnosol has enormous potential for development as a therapeutic agent for autoimmune diseases such as MS.


Subject(s)
Abietanes/pharmacology , Cell Differentiation/drug effects , Microglia/drug effects , Microglia/immunology , Th17 Cells/cytology , Th17 Cells/drug effects , Animals , Biomarkers , Cytokines , Encephalomyelitis, Autoimmune, Experimental , Female , Immunomodulation/drug effects , Immunophenotyping , Macrophages/drug effects , Macrophages/immunology , Macrophages/metabolism , Mice , Microglia/metabolism , Multiple Sclerosis/immunology , Multiple Sclerosis/metabolism , Multiple Sclerosis/pathology , NF-kappa B/metabolism , Phenotype , Phosphorylation , STAT3 Transcription Factor/metabolism , T-Lymphocyte Subsets/drug effects , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Th17 Cells/immunology , Th17 Cells/metabolism
14.
J Agric Food Chem ; 66(15): 3783-3792, 2018 Apr 18.
Article in English | MEDLINE | ID: mdl-29613792

ABSTRACT

The nutshell of Xanthoceras sorbifolia, a waste product in the production of edible oil, is rich in health-promoting phenolic acids. However, the individual constituents, bioactivities, and mechanism of action are largely unknown. In this study, 20 phenolic compounds were characterized in nutshell extract (NE) of X. sorbifolia by gas chromatography-mass spectrometry. Four established in vitro studies showed that NE has significant antioxidant potential. Results in vivo indicated that oral administration of NE effectively ameliorated clinical disease severity of experimental autoimmune encephalomyelitis (EAE) and reduced the neuroinflammation and the central nervous system (CNS) demyelination. The underlying mechanism of NE-induced effects involved decreased penetration of pathogenic immunocyte into the CNS, a reduced production of proinflammatory cytokines and factors, and suppressed differentiation of type 1 T helper and type 17 T helper cells through the Janus kinase/signal transducer and activator of transcription pathway. Taken together, our studies showed that X. sorbifolia nutshell, considered a waste material in the food industry, is a novel source of a natural antioxidant and immunomodulator.


Subject(s)
Anti-Inflammatory Agents/administration & dosage , Antioxidants/administration & dosage , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Phenols/administration & dosage , Plant Extracts/administration & dosage , Sapindaceae/chemistry , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Antioxidants/chemistry , Antioxidants/isolation & purification , Cytokines/genetics , Cytokines/immunology , Encephalomyelitis, Autoimmune, Experimental/genetics , Encephalomyelitis, Autoimmune, Experimental/immunology , Female , Humans , Mice , Mice, Inbred C57BL , Nuts/chemistry , Phenols/chemistry , Phenols/isolation & purification , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Th1 Cells/drug effects , Th1 Cells/immunology , Th17 Cells/drug effects , Th17 Cells/immunology
15.
Mitochondrial DNA B Resour ; 3(2): 480-481, 2018 Apr 23.
Article in English | MEDLINE | ID: mdl-33474212

ABSTRACT

Angelica tsinlingensis is endemic in Shaanxi province (China), and is used as Angelica sinensis in folk. Owing to important medicinal value, wild A. sinensis has been over-exploited and become quite rare in China during over 2000 years. Angelica sensu lato (s.l.; Apiaceae subfamily Apioideae) is a taxonomically complex and controversial group, and A. tsinlingensis is clearly different from members of the Angelica s.s. clade with the morphological and molecular results. The complete chloroplast DNA sequence of A. tsinlingensis (GenBank accession number: MF924726) was determined in our study. The size of chloroplast genome of A. tsinlingensis is 147,104 bp, including a large single-copy (LSC) region of 93376 bp and a small single-copy (SSC) region of 17,574 bp separated by a pair of identical inverted repeat regions (IRs) of 18,077 bp each. A total of 125 genes were successfully annotated containing 83 protein-coding genes, 34 tRNA genes and 8 rRNA genes. GC content of IRs region is the highest (44.5%). The result of Phylogenomic analysis supports the difference of A. tsinlingensis from Angelica s.s. clade.

16.
Mol Ther ; 26(2): 582-592, 2018 02 07.
Article in English | MEDLINE | ID: mdl-29275848

ABSTRACT

MicroRNAs (miRNAs) are small, non-coding RNAs involved in immune response regulation. Specific miRNAs have been linked to the development of various autoimmune diseases; however, their contribution to the modulation of CNS-directed cellular infiltration remains unclear. In this study, we found that miR-23b, in addition to its reported functions in the suppression of IL-17-associated autoimmune inflammation, halted the progression of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), by directly inhibiting the migration of pathogenic leukocytes to the CNS. We demonstrated that miR-23b was specifically decreased during the acute phase of EAE and that overexpression of miR-23b resulted in a defect in leukocyte migration and strong resistance to EAE. Furthermore, we found that miR-23b suppressed leukocyte migration of EAE by targeting CCL7, a chemokine that attracts monocytes during inflammation and metastasis. Finally, in the adoptive transfer model, miR-23b reduced the severity of EAE by inhibiting the migration of pathogenic T cells to the CNS rather than diminishing the encephalitogenesis of T cells. Taken together, our results characterize a novel aspect of miR-23b function in leukocyte migration, and they identify miR-23b as a potential therapeutic target in the amelioration of MS and likely other autoimmune diseases.


Subject(s)
Chemokine CCL7/genetics , Chemotaxis, Leukocyte/genetics , Encephalomyelitis, Autoimmune, Experimental/genetics , Encephalomyelitis, Autoimmune, Experimental/immunology , Leukocytes/immunology , Leukocytes/metabolism , MicroRNAs/genetics , 3' Untranslated Regions , Animals , Encephalomyelitis, Autoimmune, Experimental/pathology , Female , Gene Expression Regulation , Immunophenotyping , Lymphocyte Activation/genetics , Lymphocyte Activation/immunology , Mice , RNA Interference , T-Lymphocytes/immunology , T-Lymphocytes/metabolism
17.
Toxicon ; 141: 65-72, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29191388

ABSTRACT

Two acidic Asp49-PLA2s with Glu6 substitution and a neutral Lys49-PLA (designated Gst-K49) were cloned from G. strauchii venom glands, their full amino acid sequences were deduced. The predominant acidic PLA2 (designated Gst-E6a) contains 124 residues and the M18W30 substitutions, while the minor acidic PLA2 (designated Gst-E6b) contains 122 residues and the V18A30 substitutions. Their sequences are most similar to those of the respective orthologous PLA2s of G. intermedius venom. Gst-E6a and Gst-E6b appear to be paralogs and possibly have different predatory targets or functions. The LC-MS/MS results indicate the presence of only three PLA2 gene products in the crude venom, the relative expression levels were in the order of Gst-E6a â‰« Gst-E6b > Gst-K49, as confirmed by qPCR results. In contrast to other Gloydius, G. strauchii venom does not contain neurotoxic or basic anticoagulant Asp49-PLA2s, but Gst-K49 is the first Lys49-PLA2 identified in Gloydius venoms. However, its venom content is relatively low and its pI value 7.3 is much lower than those of other Lys49-PLA2s and. The Lys49-PLA2 genes appear to regress in the venom of most of Gloydius and related rattlesnake, and this evolutionary regression occurred before the dispersal of Asian pitvipers to the New World.


Subject(s)
Crotalid Venoms/chemistry , Crotalinae/genetics , Phospholipases A2/chemistry , Amino Acid Sequence , Animals , Biological Evolution , Chromatography, Liquid , Crotalid Venoms/genetics , Phylogeny , Tandem Mass Spectrometry
18.
J Proteomics ; 164: 19-32, 2017 07 05.
Article in English | MEDLINE | ID: mdl-28554670

ABSTRACT

Nine distinct venom serine proteases (vSPs) of Gloydius intermedius were studied by transcriptomic, sub-proteomic and phylogenetic analyses. Their complete amino acid sequences were deduced after Expression Sequence Tag (EST) analyses followed by cDNA cloning and sequencing. These vSPs appear to be paralogs and contain the catalytic triads and 1-4 potential N-glycosylation sites. Their relative expression levels evaluated by qPCR were grossly consistent with their EST hit-numbers. The major vSPs were purified by HPLC and their N-terminal sequences matched well to the deduced sequences, while fragments of the minor vSPs were detected by LC-MS/MS identification. Specific amidolytic activities of the fractions from HPLC and anion exchange separation were assayed using four chromogenic substrates, respectively. Molecular phylogenetic tree based on the sequences of these vSPs and their orthologs revealed six major clusters, one of them covered four lineages of plasminogen activator like vSPs. N-glycosylation patterns and variations for the vSPs are discussed. The high sequence similarities between G. intermedius vSPs and their respective orthologs from American pitvipers suggest that most of the isoforms evolved before Asian pitvipers migrated to the New World. Our results also indicate that the neurotoxic venoms contain more kallikrein-like vSPs and hypotensive components than the hemorrhagic venoms. SIGNIFICANCE: Full sequences and expression levels of nine paralogous serine proteases (designated as GiSPs) of Gloydius intermedius venom have been studied. A kallikrein-like enzyme is most abundant and four isoforms homologous to venom plasminogen-activators are also expressed in this venom. Taken together, the present and previous data demonstrate that the neurotoxic G. intermedius venoms contain more hypotensive vSPs relative to other hemorrhagic pitviper venoms and the pitviper vSPs are highly versatile and diverse. Their structure-function relationships remain to be explored and compared. A novel, simplified phylogenetic tree based on the sequences of GiSPs and their closely related orthologs from other pitvipers reveals six major subtypes and offers a better understanding of vSP duplication and evolution in pitvipers of both the Old and New Worlds. It is well known that specific vSPs are potential therapeutic or diagnostic agents that target the plasma proteins or coagulation factors. Our results not only render deeper insights into the variation and evolution of vSPs, but may help to choose right venoms for the development of better therapeutic leads.


Subject(s)
Crotalid Venoms/genetics , Crotalinae/genetics , Phylogeny , Reptilian Proteins/genetics , Sequence Analysis, Protein , Serine Proteases/genetics , Animals
19.
J Agric Food Chem ; 64(41): 7760-7769, 2016 Oct 19.
Article in English | MEDLINE | ID: mdl-27690419

ABSTRACT

Tanshinones are a group of active diterpenes with pharmacological properties that are widely used in the treatment of cardiovascular diseases. Jasmonate (JA) acts as an elicitor to enhance tanshinone biosynthesis in Salvia miltiorrhiza. However, because of high labor costs and undesirable chemical characteristics, the use of JA elicitation is still in the experimental stage. In our experiments, the overexpression of Lycopersicon esculentum (tomato) Prosystemin (LePS) in transgenic plants of S. miltiorrhiza increased their JA concentrations, significantly enhanced the production of tanshinone, and activated the expression of key genes in the tanshinone biosynthesis pathway. Meanwhile, the relative levels of metabolites related to defense such as sterols, terpenes, and phenolic acids were also increased in our OEP lines. In addition, when the larvae of cotton bollworms (Heliothis armigera) were fed with leaves from transgenic lines, their mortality rates rose by nearly 4-fold when compared to that of larvae exposed to leaves from the nontransformed wild type. Our study provides a new strategy for genetic engineering by which tanshinone production and pest resistance can be improved in S. miltiorrhiza. This is accomplished by simulating the wounding signal that increases the endogenous levels of JA.

20.
Mitochondrial DNA A DNA Mapp Seq Anal ; 27(5): 3167-8, 2016 09.
Article in English | MEDLINE | ID: mdl-25707416

ABSTRACT

The complete mitochondrial genome of the Sara Longwing Heliconius sara has been reconstructed from the whole-genome Illumina sequencing data. The mitochondrial genome is 15,372 bp in size with the highly asymmetric overall A + T content of 80.6%. Annotation of mitochondrial genome revealed a total of 37 genes, including 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), 2 ribosomal RNAs (rRNAs) and 1 D-loop region. Most PCGs are initiated with the ATN codons, while COX1 and ND1 start with CGA and TTG, respectively. COX1, COX2, and ND4 harbor the incomplete stop codon T, while all the others are terminated with the TAR codons. The complete mitochondrial genome of H. Sara would contribute to our further understanding of the phylogeny and evolution of the genus Heliconius and related taxa.


Subject(s)
Butterflies/genetics , Genome, Mitochondrial , Animals , Base Composition , Butterflies/classification , Codon/genetics , Cyclooxygenase 1/genetics , Insect Proteins/genetics , NADH Dehydrogenase/genetics , Phylogeny , RNA, Ribosomal/genetics , RNA, Transfer/genetics
SELECTION OF CITATIONS
SEARCH DETAIL
...