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1.
Int J Neurosci ; : 1-13, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38164693

RESUMO

INTRODUCTION: The metabotropic glutamate receptor 4 (mGlu4, GRM4) exhibits significant expression within the central nervous system (CNS) and has been implicated to be correlated with a poor prognosis. OBJECTIVE: This study was aimed to elucidate the relationship between the expression profile of GRM4 and the prognosis of glioma patients. METHODS: RNA-sequencing datasets from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and China Glioma Genome Atlas (CGGA) repositories were used to evaluate the potential relationship. The value of clinical prognostic about GRM4 was assessed using clinical survival data from CGGA and TCGA. The GEPIA database was used to select genes like GRM4. PPI network was constructed by the database of (STRING), GO and KEGG analyses were performed. TargetScan, TarBase, miRDB, and starBase were used to explore miRNAs that could regulate GRM4 expression. EWAS Data Hub, MethSurv, and MEXPRESS were used for the analysis and relationship between DNA methylation and GRM4 expression and prognosis in glioma. TIMER2.0 and CAMOIP databases were used to assess the association between immune cell infiltration and GRM4. Human GBM cell lines were used to validate the function of GRM4. RESULTS: Our study shows that GRM4 is under expressed among gliomas and accompanied by poorer OS. Multivariate analysis showed that low mRNA expression of GRM4 was an independent factor of prognostic for shorter OS in all glioma patients. MiR-1262 affects the malignant phenotype of gliomas through GRM4. Methylation of DNA plays an important role in the instruction of GRM4 expression, the methylation level of GRM4 in glioma tissue is higher in comparison to normal tissue, and the higher methylation level was accompanied with the worse prognosis. Further analysis showed that GRM4 mRNA expression in GBM linked negatively with common lymphoid progenitor, Macrophage M1, Macrophage, and T cell CD4+ Th2, but not with the tumor purity. Overexpression of GRM4 prevents the migration of human GBM cell lines in vitro. CONCLUSION: GRM4 may have a substantial impact on the infiltration of immune cells and serve as a valuable prognostic biomarker in gliomas.

2.
Eur J Pharmacol ; 962: 176228, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38042462

RESUMO

OBJECTIVE: G protein-coupled receptor 124 (GPR124) regulates central nervous system angiogenesis and blood-brain barrier (BBB) integrity, and its deficiency aggravates BBB breakdown and hemorrhagic transformation in ischemic mice. However, excessive GPR124 expression promotes inflammation in atherosclerotic mice. In this study, we aimed to elucidate the role of GPR124 in hypoxia/ischemia-induced cerebrovascular endothelial cell injury. METHODS: bEnd.3 cells were exposed to oxygen-glucose deprivation (OGD), and time-dependent changes in GPR124 mRNA and protein expression were evaluated using reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. The effects of GPR124 overexpression or knockdown on the expression of pyroptosis-related genes were assessed at the mRNA and protein levels. Tadehaginoside (TA) was screened as a potential small molecule targeting GPR124, and its effects on pyroptosis-related signaling pathways were investigated. Finally, the therapeutic efficacy of TA was evaluated using a rat model of transient middle cerebral artery occlusion/reperfusion (tMCAO/R). RESULTS: During OGD, the expression of GPR124 initially increased and then decreased over time, with the highest levels observed 1 h after OGD. The overexpression of GPR124 enhanced the OGD-induced expression of NLRP3, Caspase-1, and Gasdermin D (GSDMD) in bEnd.3 cells, whereas GPR124 knockdown reduced pyroptosis. Additionally, TA exhibited a high targeting ability to GPR124, significantly inhibiting its function and expression and suppressing the expression of pyroptosis-related proteins during OGD. Furthermore, TA treatment significantly reduced the cerebral infarct volume and pyroptotic signaling in tMCAO/R rats. CONCLUSIONS: Our findings suggest that GPR124 mediates pyroptotic signaling in endothelial cells during the early stages of hypoxia/ischemia, thereby exacerbating ischemic injury.


Assuntos
Inflamassomos , Traumatismo por Reperfusão , Animais , Camundongos , Ratos , Células Endoteliais/metabolismo , Glucose/metabolismo , Hipóxia/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Oxigênio/metabolismo , Piroptose , Receptores Acoplados a Proteínas G/metabolismo , Traumatismo por Reperfusão/metabolismo , RNA Mensageiro/metabolismo
3.
Clin Exp Rheumatol ; 41(12): 2502-2510, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38149512

RESUMO

OBJECTIVES: The mechanisms by which total glucosides of paeony (TGP) mitigates Sjögren's syndrome (SS) remains elusive. In the present study, we aim to explore the relationship between the therapeutic effects of TGP in the treatment of SS and NLRP3 inflammasome activation in submandibular gland (SG) cells. METHODS: Female non-obese diabetic (NOD) mice were selected as the model of SS. The mice were divided into PBS and TGP treatment group. For treatment, TGP (400mg·kg-1) was administered intragastrically every day for 4 weeks. The SS-like symptoms and pathological changes of the SG of mice were compared between the PBS and TGP group. The activation of NLRP3 inflammasome in SG was detected by RT-qPCR, immunohistochemistry and western blot. The SG cells stimulated by lipopolysaccharide (LPS) and adenosine triphosphate (ATP) for activation of NLRP3 inflammasome were treated with or without TGP. Then, NLRP3 inflammasome activation was assessed. The IL-1ß and IL-18 in homogenate of SG, serum and supernatant were detected by ELISA. RESULTS: Compared with balb/c mice, NOD mice showed SS-like symptoms and lymphocyte infiltration in SG, and the expression of NLRP3 inflammasome in SG was significantly increased. The SS-like symptoms were alleviated, and lymphocyte infiltration in SG was reduced, and the level of NLRP3 inflammasome in SG mice was decreased after TGP treatment. TGP also significantly inhibit the activation of NLRP3 inflammasome of SG cells in vitro. CONCLUSIONS: Collectively, our results indicated that TGP alleviates SS through inhibition of the activation of NLRP3 inflammasome of SG. These findings clarified the mechanism underlying the therapeutic effects of TGP on SS, and provided new evidence for the further application of TGP in the treatment of SS.


Assuntos
Paeonia , Síndrome de Sjogren , Feminino , Animais , Camundongos , Síndrome de Sjogren/tratamento farmacológico , Síndrome de Sjogren/patologia , Glândula Submandibular , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Paeonia/metabolismo , Camundongos Endogâmicos NOD
4.
Nat Commun ; 14(1): 6259, 2023 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-37802986

RESUMO

Arabidopsis thaliana serves as a model species for investigating various aspects of plant biology. However, the contribution of genomic structural variations (SVs) and their associate genes to the local adaptation of this widely distribute species remains unclear. Here, we de novo assemble chromosome-level genomes of 32 A. thaliana ecotypes and determine that variable genes expand the gene pool in different ecotypes and thus assist local adaptation. We develop a graph-based pan-genome and identify 61,332 SVs that overlap with 18,883 genes, some of which are highly involved in ecological adaptation of this species. For instance, we observe a specific 332 bp insertion in the promoter region of the HPCA1 gene in the Tibet-0 ecotype that enhances gene expression, thereby promotes adaptation to alpine environments. These findings augment our understanding of the molecular mechanisms underlying the local adaptation of A. thaliana across diverse habitats.


Assuntos
Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Genoma , Ecossistema , Tibet
5.
Int J Biol Macromol ; 253(Pt 3): 126883, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37709222

RESUMO

Considering the growing threats to the environment and human health, such as plastic pollution and food spoilage, the development of naturally antibacterial food packaging materials with biodegradable capabilities has recently attracted considerable attention. This work applies the concept of green environmental protection to packaging technology, and a new type of green edible antibacterial packaging film was developed. The basic idea is to incorporate furoic acid (FA), which possesses excellent antibacterial activity, into the flaxseed gum and konjac glucomannan matrix (FK) as a filler to obtain a series of FK-FA bioactive films. This incorporation simultaneously improves the hydrophobicity and UV-barrier ability by 12.28 % and 42.87 %, respectively. Meanwhile, the diameters of the antibacterial zone of the FK-FA0.4% films (composite FK films containing 0.4 % FA) against E. coli and S. aureus increased to 38.98 mm and 36.29 mm from 24.00 mm of pure FK film, respectively. As a consequence, the grape sample sealed with FK-FA0.4% film remained edible on the 18th day of storage, while those packaged with commercial PE film and pure FK were seriously rotted and lost edible value on the 12th day, further confirming the enhanced preservation capacity. Finally, the as-prepared films were established to be biodegradable and were almost completely degraded within 25 days under simulated environmental conditions. Overall, these promising results show the potential of FK-FA films for replacing plastic packaging materials as eco-friendly edible films with prolonged shelf life for active packaging.


Assuntos
Linho , Vitis , Humanos , Escherichia coli , Staphylococcus aureus , Antibacterianos/farmacologia , Embalagem de Alimentos/métodos , Ácidos
6.
Sci Rep ; 13(1): 9771, 2023 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-37328486

RESUMO

T-box transcription factor 15 (TBX15) is upregulated in a variety of tumors and has been reported to promote uncontrolled proliferation of tumor cells and induce tumor cells to avoid apoptosis, thus accelerating the malignant transformation of malignant tumors. However, the prognostic value of TBX15 in glioma and its relationship with immune infiltration remain unknown. In this study, we intended to explore the prognostic value of TBX15 and its link to glioma immune infiltration and examine TBX15 expression in pan-cancer using RNAseq data in TPM format from TCGA and GTEx. TBX15 mRNA and protein expressions in glioma cells and adjacent normal tissue were detected and compared by RT-qPCR and Western blot. The effect of TBX15 on survival was assessed by Kaplan-Meier Method. The correlation between TBX15 upregulation and the clinicopathological characteristics of glioma patients was assessed by using TCGA databases, and the relationship between TBX15 and other genes in glioma was evaluated by using TCGA data. The top 300 genes most significantly associated with TBX15 were selected to establish a PPI network through the STRING database. The relationship between TBX15 mRNA expression and immune cell infiltration was explored by using ssGSEA and the TIMER Database. It was found that TBX15 mRNA expression in glioma tissues was significantly higher than that in the adjacent normal tissues, and this difference was most obvious in high-grade gliomas. TBX15 expression was increased in human gliomas and associated with worse clinicopathological characteristics and poorer survival prognosis in glioma patients. In addition, elevated TBX15 expression was linked to a collection of genes involved in immunosuppression. In conclusion, TBX15 played an important role in immune cell infiltration in glioma and may prove to be a predictor of the prognosis in glioma patients.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/patologia , Relevância Clínica , Glioma/patologia , Prognóstico , RNA Mensageiro/genética , Proteínas com Domínio T/genética
7.
Immunology ; 170(2): 286-300, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37337447

RESUMO

Although various studies have been performed on the function of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in RA, the results were conflicting. Here we were trying to clarify the role of PMN-MDSCs in the pathogenesis of RA and its specific mechanisms. We detected the frequencies and counts of PMN-MDSCs, TNF-α+ B cells and Ki67+ B cells in spleen and inflamed joints of collagen-induced arthritis (CIA) mice using flow cytometry. The pathological role of PMN-MDSCs was examined by anti-Ly6G neutralizing antibodies against PMN-MDSCs or adoptive transfer of PMN-MDSCs. And the modulation of PMN-MDSCs on B cells was conducted by coculture assays, RNA-Seq, RT-qPCR, and so on. The mechanism of BAFF regulating B cells was verified through western blot and flow cytometry. PMN-MDSCs accumulated in the spleen and joints of CIA mice. PMN-MDSCs depletion could alleviate the arthritis severity, which was accompanied by decreased TNF-α secretion and proliferation of B cells. And its adoptive transfer also facilitated disease progress. Furthermore, PMN-MDSCs from CIA mice had higher expression level of BAFF, which regulated TNF-α expression, proliferation and apoptosis of B cells in vitro. What's more, BAFF promoted phosphorylation of BTK/NF-κB signalling pathway. And Ibrutinib (BTK inhibitor) could reverse the effect of BAFF on TNF-α expression of B cells. Our study suggested that PMN-MDSCs enhanced disease severity of CIA and manipulated TNF-α expression, proliferation and apoptosis of B cells via BAFF, furthermore, BAFF promoted TNF-α expression through BTK/NF-κB signalling pathway, which demonstrated a novel pathogenesis of PMN-MDSCs in CIA.


Assuntos
Artrite Experimental , Células Supressoras Mieloides , Camundongos , Animais , NF-kappa B/metabolismo , Células Supressoras Mieloides/metabolismo , Fator de Necrose Tumoral alfa , Transdução de Sinais
8.
Angew Chem Int Ed Engl ; 62(23): e202302126, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37051748

RESUMO

Supramolecular self-assembly is a promising strategy for stabilizing the photo-sensitive components in photocatalysis. However, the underlying correlation between the enhanced photostability and supramolecular structure at the molecular level has not yet been fully understood. Herein, we develop a biomimetic vesicular membrane-based polyporphyrin photocatalyst exhibiting excellent photocatalytic stability with at least activity time of 240 h in hydrogen generation. Time-domain ab initio modelling together with transient absorption spectroscopy, visual frontier orbitals and Gibbs free energy calculation disclose that the ordered aggregation of porphyrin units in the vesicle membrane facilitates "hot" electron relaxation and the rapid dissipation of photo-generated charges, thereby contributing to the longevity. This work deepens the molecular-level understanding on photostability and photocatalytic mechanism of supramolecular photocatalysts.

9.
Food Chem X ; 17: 100529, 2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-36845468

RESUMO

Chloropropanols, one of the major contaminants in food, and the corresponding esters or glycidyl esters (GEs) are of great concern in terms of product safety due to their potential carcinogenicity. During heat processing, glycerol, allyl alcohol, chloropropanol esters, sucralose, and carbohydrate in mixed foodstuffs are probable precursors of chloropropanol. The standard analytical techniques for chloropropanols or their esters are GC-MS or LC-MS following sample derivatization pretreatment. By comparing modern data against that five-year-old before, it appears that the levels of chloropropanols and their esters/GEs in food products have somewhat decreased. 3-MCPD esters or GEs may yet exceed the permitted intake set, however, especially in newborn formula which requires particularly stringent regulatory measures. Citespace (6.1. R2) software was employed in this study to examine the research focii of chloropropanols and their corresponding esters/GEs in the literature.

10.
Int Immunopharmacol ; 115: 109625, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36586275

RESUMO

Aberrant neutrophil extracellular traps (NETs) are involved in the pathogenesis of rheumatoid arthritis (RA). However, the specific pathway leading to NET formation in RA is poorly understood. Therefore, therapies targeting NETs are not available in RA. In this study, we demonstrated Src homology 2 domain-containing inositol phosphatase-1 (SHIP1) function as a hub to regulate NETosis through SHIP1/ p38 MAPK/TNF-α pathway both in vitro and ex vivo and inhibiting SHIP1 expression ameliorated RA symptoms in vivo. Neutrophils from RA patients showed enhanced NETosis as well as increased SHIP1, p38 mitogen-activated protein kinase (MAPK) family expression and tumor necrosis factor-α (TNF-α) expression. Inhibiting SHIP1 in neutrophils using small molecules counteracted the above-mentioned dysregulations and resulted in decrease in NETosis, p38 expression and TNF-α concentration. Consistent with this, SHIP1 agonist led to upregulated p38MAPK and NET formation. Moreover, inhibiting SHIP1 in vivo led to decreased NETosis and showed beneficial therapeutic effects in Collagen-induced arthritis (CIA) mice. Taken together, these results indicated that activation of SHIP1/MAPK/TNF-α pathway was necessary for upregulated NETosis in RA, which provided evidence for targeting SHIP1 in RA treatment.


Assuntos
Artrite Reumatoide , Armadilhas Extracelulares , Animais , Camundongos , Artrite Reumatoide/metabolismo , Neutrófilos , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases/genética , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
11.
BMC Cardiovasc Disord ; 22(1): 339, 2022 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-35906548

RESUMO

BACKGROUND: Coronary atherosclerosis (CA) is the most common type of atherosclerosis. However, the inherent pathogenesis and mechanisms of CA are unclear, and the relationship with ferroptosis-related genes (FRGs) has not been reported. The purpose of this study was to use bioinformatics techniques to evaluate potential therapeutic targets for CA.Please provide the given name for author "Dingshun".Please provide the given name for author "Dingshun". METHODS: First, the GSE132651 dataset was acquired from the Gene Expression Omnibus database. Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and Protein-Protein interaction network were successively conducted. Next, overlapping genes between hub genes and CA genes were found. FRGs were found when comparing the CA group with the normal group. The correlation between overlapping genes and FRGs was further analyzed. At last, we performed Elisa to validate the expression of these genes in human blood specimens. Mice aortic tissues were used for western blot to detect the expression of proteins. RESULTS: Based on the GSE132651 dataset, 102 differentially expressed genes were identified. Five overlapping genes between hub genes and CA genes were found (CCNA2, RRM2, PBK, PCNA, CDK1). TFRC and GPX4 were found to be FRGs. TFRC was positively correlated with CCNA2, PBK, PCNA, CDK1, RRM2, with CDK1 being the strongest correlation. GPX4 was negatively correlated with these genes, among which CCNA2 was the strongest correlation. The ELISA results showed that CCNA2, CDK1, and TFRC expression were markedly increased in serum of the CA samples compared with controls, while GPX4 expression was markedly decreased in the CA samples. The western blot results show that GPX4 expression was lower in the model group, TFRC, CDK1, and CCNA2 protein expression were high in the model group. CONCLUSIONS: Ferroptosis-related genes GPX4 and TFRC were closely correlated with the identified overlapping genes CCNA2 and CDK1, which may serve as targeted therapies for the treatment of CA.


Assuntos
Doença da Artéria Coronariana , Ferroptose , Animais , Biologia Computacional/métodos , Doença da Artéria Coronariana/genética , Ferroptose/genética , Humanos , Camundongos , Antígeno Nuclear de Célula em Proliferação
12.
Comput Intell Neurosci ; 2022: 1746472, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35665284

RESUMO

Web videos have gradually replaced text, voice, pictures, and other information carriers to become an important way of information dissemination in the new media era. As digital technology brings a new dissemination ecology, the original dissemination trust theory and its framework are facing the crisis of explanatory power failure. This paper considers the popular science web video as an object of study. It analyses and interprets the development of popular science web videos based on the evolution of dissemination form and the basic principle of social trust, from perspectives such as mediology, informatics, and sociology. To maintain or improve the trust relationship in web videos, it's necessary to find positive incentive and reverse punishment, and establish a trust certification and regulation mechanism. In this way, active dissemination and sharing of information can be promoted for a more vigorous society and culture. Moreover, this paper explores a new way of web video development from the perspective of trust.


Assuntos
Mídias Sociais , Confiança , Disseminação de Informação , Gravação em Vídeo
13.
Artigo em Inglês | MEDLINE | ID: mdl-35607519

RESUMO

Safflower has long been used to treat coronary heart disease (CHD). However, the underlying mechanism remains unclear. The goal of this study was to predict the therapeutic effect of safflower against CHD using a network pharmacology and to explore the underlying pharmacological mechanisms. Firstly, we obtained relative compounds of safflower based on the TCMSP database. The TCMSP and PubChem databases were used to predict targets of these active compounds. Then, we built CHD-related targets by the DisGeNET database. The protein-protein interaction (PPI) network graph of overlapping genes was obtained after supplying the common targets of safflower and CHD into the STRING database. The PPI network was then used to determine the top ten most significant hub genes. Furthermore, the DAVID database was utilized for the enrichment analysis on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). To validate these results, a cell model of CHD was established in EAhy926 cells using oxidized low-density lipoprotein (ox-LDL). Safflower was determined to have 189 active compounds. The TCMSP and PubChem databases were used to predict 573 targets of these active compounds. The DisGeNET database was used to identify 1576 genes involved in the progression of CHD. The top ten hub genes were ALB, IL6, IL1B, VEGFA, STAT3, MMP9, TLR4, CCL2, CXCL8, and IL10. GO functional enrichment analysis yielded 92 entries for biological process (BP), 47 entries for cellular component (CC), 31 entries for molecular function (MF), and 20 signaling pathways, which were obtained from KEGG pathway enrichment screening. Based on these findings, the FoxO signaling pathway is critical in the treatment of CHD by safflower. The in vitro results showed that safflower had an ameliorating effect on ox-LDL-induced apoptosis and mitochondrial membrane potential. The western blot results showed that safflower decreased Bax expression and acetylation of FoxO1 proteins while increasing the expression of Bcl-2 and SIRT1 proteins. Safflower can be used in multiple pathways during CHD treatment and can exert anti-apoptotic effects by regulating the expression of Bax, Bcl-2, and SIRT1/FoxO1 signaling pathway-related proteins.

14.
ACS Appl Mater Interfaces ; 14(18): 21198-21206, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35475613

RESUMO

The reproducible fabrication of large-area zeolite membranes for gas separation is still a great challenge. We report the scalable fabrication of high-performance zeolite MFI membranes by single-step secondary growth on the 19-channel alumina monoliths for the first time. The packing density and mechanical strength of the monolithic membranes are much higher for these than for tubular ones. Separation performance of the monolithic membranes toward the butane isomer mixture was comparably evaluated using the vacuum and Wicke-Kallenbach modes. The n-butane permeances and n-butane/i-butane separation factors for the three membranes with an effective area of ∼84 cm2 were >1.0 × 10-7 mol (m2 s Pa)-1 and >50 at 343 K for an equimolar n-butane/i-butane mixture, respectively. We succeeded in scaling up the membrane synthesis with the largest area of 270 cm2 to date which has 1.3 times the area of an industrial 1 m long tubular membrane. Monolith supported zeolite MFI membranes show great potential for industrial n-butane/i-butane separation.

15.
Natl Sci Rev ; 9(12): nwac276, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36687562

RESUMO

Radiations are especially important for generating species biodiversity in mountainous ecosystems. The contribution of hybridization to such radiations has rarely been examined. Here, we use extensive genomic data to test whether hybridization was involved in evolutionary radiation within Rhododendron subgenus Hymenanthes, whose members show strong geographic isolation in the mountains of southwest China. We sequenced genomes for 143 species of this subgenus and 93 species of four other subgenera, and found that Hymenanthes was monophyletic and radiated during the late Oligocene to middle Miocene. Widespread hybridization events were inferred within and between the identified clades and subclades. This suggests that hybridization occurred both early and late during diversification of subgenus Hymenanthes, although the extent to which hybridization, speciation through mixing-isolation-mixing or hybrid speciation, accelerated the diversification needs further exploration. Cycles of isolation and contact in such and other montane ecosystems may have together promoted species radiation through hybridization between diverging populations and species. Similar radiation processes may apply to other montane floras in this region and elsewhere.

16.
BMC Complement Med Ther ; 21(1): 202, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34284768

RESUMO

BACKGROUND: Gout is initiated by the precipitation of monosodium urate (MSU) crystals within the joints and soft tissues, and it can eventually cause acute or chronic arthritis. MSU crystals trigger, amplify, and maintain a strong inflammatory response through promoting proinflammatory activity. In this study, the therapeutic effects of Stephania hainanensis (S. hainanensis) total alkaloid (SHA) were tested and evaluated on MSU-induced acute gouty arthritis in a mouse model. METHODS: After oral administration of SHA (10 or 20 mg/kg) or the antigout medicine colchicine (0.5 mg/kg) once daily for 3 consecutive days, MSU crystals suspended in saline (2.5 mg/50 µl) were intradermally injected into the right paw of the mice. Then, SHA and colchicine were administered for another 2 days. During this period, swelling of the ankle and clinical scores were measured at 12, 24, and 48 h postinjection. After the mice were euthanized, inflammatory cytokine expression and paw tissue inflammation-related gene and protein expression, and a histopathological analysis was performed. RESULTS: SHA had obvious therapeutic effects on MSU-induced acute gouty arthritis in mice. SHA alleviated ankle swelling and inhibited the production of cytokines, such as IL-1ß and TNF-α. In addition, NLRP3, Caspase-1 and IL-1ß, which are activated by MSU were also suppressed by SHA. The histological evaluation showed that SHA relieved the infiltration of inflammation around the ankle. CONCLUSIONS: These results suggest that SHA is capable of anti-inflammatory activities and may be useful for treating gouty arthritis.


Assuntos
Alcaloides/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/toxicidade , Artrite Gotosa/induzido quimicamente , Stephania/metabolismo , Ácido Úrico/toxicidade , Animais , Antioxidantes/farmacologia , Camundongos
17.
Chem Commun (Camb) ; 56(99): 15496-15512, 2020 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-33300513

RESUMO

Bioinspired transformation of small-molecules to energy-related feedstocks is an attractive research area to overcome both the environmental issues and the depletion of fossil fuels. The highly effective metalloenzymes in nature provide blueprints for the utilization of bioinspired metal complexes for artificial photosynthesis. Through simpler structural and functional mimics, the representative herein is the pivotal development of several critical small molecule conversions catalyzed by metal complexes, e.g., water oxidation, proton and CO2 reduction and organic chemical transformation of small molecules. Of great achievement is the establishment of bioinspired metal complexes as catalysts with high stability, specific selectivity and satisfactory efficiency to drive the multiple-electron and multiple-proton processes related to small molecule transformation. Also, potential opportunities and challenges for future development in these appealing areas are highlighted.


Assuntos
Complexos de Coordenação/metabolismo , Metaloproteínas/metabolismo , Bibliotecas de Moléculas Pequenas/metabolismo , Catálise , Complexos de Coordenação/química , Metaloproteínas/química , Processos Fotoquímicos , Bibliotecas de Moléculas Pequenas/química
18.
Org Lett ; 22(10): 3804-3809, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32343142

RESUMO

Direct C-S bond coupling is an attractive way to construct aryl sulfur ether, a building block for a variety of biological active molecules. Herein, we disclose an effective model for regioselective thiolation of the aromatic C-H bond by thiol activation instead of arene activation. Strikingly, this method has been applied into anisole derivatives that are not available in the arene activation approach to forge a single thioether isomer with high reactivity.

19.
Hortic Res ; 7: 18, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32025321

RESUMO

Isatis indigotica (2n = 14) is an important medicinal plant in China. Its dried leaves and roots (called Isatidis Folium and Isatidis Radix, respectively) are broadly used in traditional Chinese medicine for curing diseases caused by bacteria and viruses such as influenza and viral pneumonia. Various classes of compounds isolated from this species have been identified as effective ingredients. Previous studies based on transcriptomes revealed only a few candidate genes for the biosynthesis of these active compounds in this medicinal plant. Here, we report a high-quality chromosome-scale genome assembly of I. indigotica with a total size of 293.88 Mb and scaffold N50 = 36.16 Mb using single-molecule real-time long reads and high-throughput chromosome conformation capture techniques. We annotated 30,323 high-confidence protein-coding genes. Based on homolog searching and functional annotations, we identified many candidate genes involved in the biosynthesis of main active components such as indoles, terpenoids, and phenylpropanoids. In addition, we found that some key enzyme-coding gene families related to the biosynthesis of these components were expanded due to tandem duplications, which likely drove the production of these major active compounds and explained why I. indigotica has excellent antibacterial and antiviral activities. Our results highlighted the importance of genome sequencing in identifying candidate genes for metabolite synthesis in medicinal plants.

20.
Mol Ecol Resour ; 20(3)2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32034885

RESUMO

Populus euphratica is well adapted to extreme desert environments and is an important model species for elucidating the mechanisms of abiotic stress resistance in trees. The current assembly of P. euphratica genome is highly fragmented with many gaps and errors, thereby impeding downstream applications. Here, we report an improved chromosome-level reference genome of P. euphratica (v2.0) using single-molecule sequencing and chromosome conformation capture (Hi-C) technologies. Relative to the previous reference genome, our assembly represents a nearly 60-fold improvement in contiguity, with a scaffold N50 size of 28.59 Mb. Using this genome, we have found that extensive expansion of Gypsy elements in P. euphratica led to its rapid increase in genome size compared to any other Salicaceae species studied to date, and potentially contributed to adaptive divergence driven by insertions near genes involved in stress tolerance. We also detected a wide range of unique structural rearrangements in P. euphratica, including 2,549 translocations, 454 inversions, 121 tandem and 14 segmental duplications. Several key genes likely to be involved in tolerance to abiotic stress were identified within these regions. This high-quality genome represents a valuable resource for poplar breeding and genetic improvement in the future, as well as comparative genomic analysis with other Salicaceae species.


Assuntos
Genoma de Planta/genética , Populus/genética , Adaptação Fisiológica/genética , Clima Desértico , Evolução Molecular , Regulação da Expressão Gênica de Plantas/genética , Genes de Plantas/genética , Estresse Fisiológico/genética , Árvores/genética
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