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1.
Immunity ; 54(8): 1728-1744.e7, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34343498

RESUMO

Inflammatory bowel disease (IBD) mainly includes Crohn's disease (CD) and ulcerative colitis (UC). Immune disorders play an essential role in the pathogenesis of these two IBDs, but the differences in the immune microenvironment of the colon and their underlying mechanisms remain poorly investigated. Here we examined the immunological features and metabolic microenvironment of untreated individuals with IBD by multiomics analyses. Modulation of CD-specific metabolites, particularly reduced selenium, can obviously shape type 1 T helper (Th1) cell differentiation, which is specifically enriched in CD. Selenium supplementation suppressed the symptoms and onset of CD and Th1 cell differentiation via selenoprotein W (SELW)-mediated cellular reactive oxygen species scavenging. SELW promoted purine salvage pathways and inhibited one-carbon metabolism by recruiting an E3 ubiquitin ligase, tripartite motif-containing protein 21, which controlled the stability of serine hydroxymethyltransferase 2. Our work highlights selenium as an essential regulator of T cell responses and potential therapeutic targets in CD.


Assuntos
Antioxidantes/farmacologia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/imunologia , Selênio/farmacologia , Selenoproteína W/metabolismo , Células Th1/citologia , Diferenciação Celular/imunologia , Polaridade Celular , Colo/imunologia , Colo/patologia , Glicina Hidroximetiltransferase/metabolismo , Humanos , Espécies Reativas de Oxigênio/metabolismo , Ribonucleoproteínas/metabolismo , Células Th1/imunologia , Ubiquitina-Proteína Ligases/metabolismo
2.
J Nanobiotechnology ; 22(1): 24, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191388

RESUMO

The iron oxide nanoparticles (IONPs), possessing both magnetic behavior and semiconductor property, have been extensively used in multifunctional biomedical fields due to their biocompatible, biodegradable and low toxicity, such as anticancer, antibacterial, cell labelling activities. Nevertheless, there are few IONPs in clinical use at present. Some IONPs approved for clinical use have been withdrawn due to insufficient understanding of its biomedical applications. Therefore, a systematic summary of IONPs' preparation and biomedical applications is crucial for the next step of entering clinical practice from experimental stage. This review summarized the existing research in the past decade on the biological interaction of IONPs with animal/cells models, and their clinical applications in human. This review aims to provide cutting-edge knowledge involved with IONPs' biological effects in vivo and in vitro, and improve their smarter design and application in biomedical research and clinic trials.


Assuntos
Antibacterianos , Nanopartículas Magnéticas de Óxido de Ferro , Animais , Humanos
3.
J Appl Biomed ; 22(1): 40-48, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38505969

RESUMO

BACKGROUND: Endoplasmic reticulum (ER) stress has been shown to play an important role in osteoarthritis (OA). OBJECTIVE: This study was aimed at assessing the relationship of endoplasmic reticulum (ER) stress-related glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP) concentrations in the serum/synovial fluid (SF) with disease severity of primary knee osteoarthritis (pkOA). METHODS: Patients with pkOA together with healthy individuals were consecutively recruited from our hospital. The levels of GRP78 and CHOP in serum / SF were detected using enzyme-linked immunosorbent assay. The levels of IL-6 and MMP-3 were also examined. Radiographic progression of pkOA was evaluated based on Kellgren-Lawrence (K-L) grades. Receiver Operating Characteristic (ROC) curves were used to assess the diagnostic value of GRP78/CHOP levels with regard to K-L grades. The assessment of clinical severity was conducted using the visual analogue scale (VAS), Oxford knee score (OKS), and Lequesne algofunctional index (LAI). RESULTS: A total of 140 pkOA patients and 140 healthy individuals were included. Serum GRP78 and CHOP levels in pkOA patients were not significantly different from those in healthy individuals. The SF GRP78 and CHOP levels in healthy controls were not detected due to ethical reasons. Compared to those with K-L grade 2 and 3, the pkOA patients with K-L grade 4 had higher GRP78 and CHOP levels in the SF with statistical significance. In addition, the pkOA patients with K-L grade 3 exhibited drastically upregulated GRP78 and CHOP concentrations in the SF compared to those with K-L grade 2. Positive correlations of GRP78 and CHOP levels with K-L grades, IL-6, and MMP-3 levels in the SF were observed. ROC curve analysis indicated that both GRP78 and CHOP levels may act as decent indicators with regard to OA. GRP78 and CHOP concentrations in the SF were positively correlated with VAS/LAI score and negatively associated with OKS score. CONCLUSION: The study indicated that GRP78 and CHOP levels in the SF but not the serum were positively correlated with disease severity of pkOA.


Assuntos
Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/diagnóstico por imagem , Líquido Sinovial/química , Líquido Sinovial/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Estudos Transversais , Chaperona BiP do Retículo Endoplasmático , Interleucina-6/metabolismo , Biomarcadores/análise , Biomarcadores/metabolismo , Progressão da Doença
4.
Plant Cell Environ ; 46(8): 2323-2336, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37303271

RESUMO

Leaf photosynthetic nitrogen-use efficiency (PNUE) diversified significantly among C3 species. To date, the morpho-physiological mechanisms and interrelationships shaping PNUE on an evolutionary time scale remain unclear. In this study, we assembled a comprehensive matrix of leaf morpho-anatomical and physiological traits for 679 C3 species, ranging from bryophytes to angiosperms, to comprehend the complexity of interrelationships underpinning PNUE variations. We discovered that leaf mass per area (LMA), mesophyll cell wall thickness (Tcwm ), Rubisco N allocation fraction (PR ), and mesophyll conductance (gm ) together explained 83% of PNUE variations, with PR and gm accounting for 65% of those variations. However, the PR effects were species-dependent on gm , meaning the contribution of PR on PNUE was substantially significant in high-gm species compared to low-gm species. Standard major axis (SMA) and path analyses revealed a weak correlation between PNUE and LMA (r2 = 0.1), while the SMA correlation for PNUE-Tcwm was robust (r2 = 0.61). PR was inversely related to Tcwm , paralleling the relationship between gm and Tcwm , resulting in the internal CO2 drawdown being only weakly proportional to Tcwm . The coordination of PR and gm in relation to Tcwm constrains PNUE during the course of evolution.


Assuntos
Nitrogênio , Folhas de Planta , Folhas de Planta/fisiologia , Plantas , Fotossíntese/fisiologia , Células do Mesofilo/fisiologia , Parede Celular , Dióxido de Carbono
5.
Am J Hematol ; 98(1): 66-78, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36219502

RESUMO

Mixed phenotype acute leukemia (MPAL) is a subtype of leukemia in which lymphoid and myeloid markers are co-expressed. Knowledge regarding the genetic features of MPAL is lacking due to its rarity and heterogeneity. Here, we applied an integrated genomic and transcriptomic approach to explore the molecular characteristics of 176 adult patients with MPAL, including 86 patients with T-lymphoid/myeloid MPAL (T/My MPAL-NOS), 42 with Ph+ MPAL, 36 with B-lymphoid/myeloid MPAL (B/My MPAL-NOS), 4 with t(v;11q23), and 8 with MPAL, NOS, rare types. Genetically, T/My MPAL-NOS was similar to B/T MPAL-NOS but differed from Ph+ MPAL and B/My MPAL-NOS. T/My MPAL-NOS exhibited higher CEBPA, DNMT3A, and NOTCH1 mutations. Ph+ MPAL demonstrated higher RUNX1 mutations. B/T MPAL-NOS showed higher NOTCH1 mutations. By integrating next-generation sequencing and RNA sequencing data of 89 MPAL patients, we defined eight molecular subgroups (G1-G8) with distinct mutational and gene expression characteristics. G1 was associated with CEBPA mutations, G2 and G3 with NOTCH1 mutations, G4 with BCL11B rearrangement and FLT3 mutations, G5 and G8 with BCR::ABL1 fusion, G6 with KMT2A rearrangement/KMT2A rearrangement-like features, and G7 with ZNF384 rearrangement/ZNF384 rearrangement-like characteristics. Subsequently, we analyzed single-cell RNA sequencing data from five patients. Groups G1, G2, G3, and G4 exhibited overexpression of hematopoietic stem cell disease-like and common myeloid progenitor disease-like signatures, G5 and G6 had high expression of granulocyte-monocyte progenitor disease-like and monocyte disease-like signatures, and G7 and G8 had common lymphoid progenitor disease-like signatures. Collectively, our findings indicate that integrative genomic and transcriptomic profiling may facilitate more precise diagnosis and develop better treatment options for MPAL.


Assuntos
Leucemia Mieloide Aguda , Transcriptoma , Humanos , Doença Aguda , Fenótipo , Genômica
6.
Phytother Res ; 37(10): 4755-4770, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37846157

RESUMO

Chronic social isolation (SI) stress, which became more prevalent during the COVID-19 pandemic, contributes to abnormal behavior, including mood changes and cognitive impairment. Known as a functional nutrient, betaine has potent antioxidant and anti-inflammatory properties in vivo. However, whether betaine can alleviate the abnormal behavior induced by chronic SI in mice remains unknown. In this study, we investigated the efficacy of betaine in the treatment of behavioral changes and its underlying mechanism. Three-week-old male mice were randomly housed for 8 weeks in either group housing (GH) or SI. The animals were divided into normal saline-treated GH, normal saline-treated SI, and betaine-treated SI groups in the sixth week. The cognitive and depression-like behavior was determined in the eighth week. We found that long-term betaine administration improved cognitive behavior in SI mice but failed to prevent depression-like behavior. Moreover, long-term betaine administration inhibited hippocampal microglia over-activation and polarized microglia toward the M2 phenotype, which effectively inhibited the expression of inflammatory factors in SI mice. Finally, the protective effect of betaine treatment in SI mice might not be due to altered activity of the hypothalamic-pituitary-adrenal axis. Collectively, our findings reveal that betaine can improve SI-induced cognitive impairment, thus providing an alternative natural source for the prevention of memory loss caused by SI or loneliness.


Assuntos
Betaína , Disfunção Cognitiva , Camundongos , Masculino , Animais , Humanos , Betaína/efeitos adversos , Betaína/metabolismo , Microglia , Sistema Hipotálamo-Hipofisário , Pandemias , Solução Salina/efeitos adversos , Solução Salina/metabolismo , Sistema Hipófise-Suprarrenal , Hipocampo , Isolamento Social/psicologia , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/induzido quimicamente
7.
Acta Pharmacol Sin ; 43(4): 797-810, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34226665

RESUMO

Newborns suffering from hypoxia-ischemia (HI) brain injury still lack effective treatment. Proline-rich tyrosine kinase 2 (Pyk2) is a non-receptor tyrosine kinase, which is highly correlated with transient ischemic brain injury in adult. In this study, we investigated the role of Pyk2 in neonatal HI brain injury. HI was induced in postnatal day 7 mouse pups by unilateral common carotid artery ligation followed by hypoxic exposure. Pyk2 interference lentivirus (LV-Pyk2 shRNA) was constructed and injected into unilateral cerebral ventricle of neonatal mice before HI. Infarct volume, pathological changes, and neurological behaviors were assessed on postnatal day 8-14. We showed that the phosphorylation level of Pyk2 was significantly increased in neonatal brain after HI, whereas LV-Pyk2 shRNA injection significantly attenuated acute HI brain damage and improved neurobehavioral outcomes. In oxygen-glucose deprivation-treated cultured cortical neurons, Pyk2 inhibition significantly alleviated NMDA receptor-mediated excitotoxicity; similar results were also observed in neonatal HI brain injury. We demonstrated that Pyk2 inhibition contributes to the long-term cerebrovascular recovery assessed by laser speckle contrast imaging, but cognitive function was not obviously improved as evaluated in Morris water maze and novel object recognition tests. Thus, we constructed lentiviral LV-HIF-Pyk2 shRNA, through which HIF-1α promoter-mediated interference of Pyk2 would occur during the anoxic environment. Intracerebroventricular injection of LV-HIF-Pyk2 shRNA significantly improved long-term recovery of cognitive function in HI-treated neonatal mice. In conclusion, this study demonstrates that Pyk2 interference protects neonatal brain from hypoxic-ischemic injury. HIF-1α promoter-mediated hypoxia conditional control is a useful tool to distinguish between hypoxic period and normal period. Pyk2 is a promising drug target for potential treatment of neonatal HI brain injury.


Assuntos
Lesões Encefálicas , Hipóxia-Isquemia Encefálica , Animais , Animais Recém-Nascidos , Encéfalo/patologia , Lesões Encefálicas/patologia , Quinase 2 de Adesão Focal/farmacologia , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Camundongos
8.
Appl Microbiol Biotechnol ; 106(2): 713-727, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34921331

RESUMO

Recent technical advances regarding filamentous fungi have accelerated the engineering of fungal-based production and benefited basic science. However, challenges still remain and limit the speed of fungal applications. For example, high-throughput technologies tailored to filamentous fungi are not yet commonly available for genetic modification. The currently used fungal genetic manipulations are time-consuming and laborious. Here, we developed a flow cytometry-based plating-free system to directly screen and isolate the transformed protoplasts in industrial fungi Myceliophthora thermophila and Aspergillus niger. This system combines genetic engineering via the 2A peptide and the CRISPR-Cas9 system, strain screening by flow cytometry, and direct sorting of colonies for deep-well-plate incubation and phenotypic analysis while avoiding culturing transformed protoplasts in plates, colony picking, conidiation, and cultivation. As a proof of concept, we successfully applied this system to generate the glucoamylase-hyperproducing strains MtYM6 and AnLM3 in M. thermophila and A. niger, respectively. Notably, the protein secretion level and enzyme activities in MtYM6 were 17.3- and 25.1-fold higher than in the host strain. Overall, these findings suggest that the flow cytometry-based plating-free system can be a convenient and efficient tool for strain engineering in fungal biotechnology. We expect this system to facilitate improvements of filamentous fungal strains for industrial applications. KEY POINTS: • Development of a flow cytometry-based plating-free (FCPF) system is presented. • Application of FCPF system in M. thermophila and A. niger for glucoamylase platform. • Hyper-produced strains MtYM6 and AnLM3 for glucoamylase production are generated.


Assuntos
Edição de Genes , Glucana 1,4-alfa-Glucosidase , Aspergillus niger/genética , Citometria de Fluxo , Engenharia Genética , Glucana 1,4-alfa-Glucosidase/genética
9.
BMC Vet Res ; 18(1): 222, 2022 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-35690747

RESUMO

BACKGROUND: Histomonas meleagridis is an anaerobic, intercellular parasite, which infects gallinaceous birds such as turkeys and chickens. In recent years, the reemergence of Histomoniasis has caused serious economic losses as drugs to treat the disease have been banned. At present, H. meleagridis research focuses on virulence, gene expression analysis, and the innate immunity of the host. However, there are no studies on the differentially expressed miRNAs (DEMs) associated with the host inflammatory and immune responses induced by H. meleagridis. In this research, high-throughput sequencing was used to analyze the expression profile of cecum miRNA at 10 and 15 days post-infection (DPI) in chickens infected with Chinese JSYZ-F strain H. meleagridis. RESULTS: Compared with the controls, 94 and 127 DEMs were found in cecum of infected chickens at 10 DPI (CE vs CC) and 15 DPI (CEH vs CCH), respectively, of which 60 DEMs were shared at two-time points. Gene Ontology (GO) functional enrichment analysis of the target genes of DEMs indicated that 881 and 1027 GO terms were significantly enriched at 10 and 15 DPI, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG, www.kegg.jp/kegg/kegg1.html ) pathway enrichment analysis of the target genes of DEMs demonstrated that 5 and 3 KEGG pathways were significantly enriched at 10 and 15 DPI, respectively. For previous uses, the Kanehisa laboratory have happily provided permission. The integrated analysis of miRNA-gene network revealed that the DEMs played important roles in the host inflammatory and immune responses to H. meleagridis infection by dynamically regulating expression levels of inflammation and immune-related cytokines. CONCLUSION: This article not only suggested that host miRNA expression was dynamically altered by H. meleagridis and host but also revealed differences in the regulation of T cell involved in host responses to different times H. meleagridis infection.


Assuntos
MicroRNAs , Doenças das Aves Domésticas , Infecções Protozoárias em Animais , Trichomonadida , Animais , Ceco , Galinhas/parasitologia , MicroRNAs/genética , Doenças das Aves Domésticas/parasitologia , Trichomonadida/genética , Perus
10.
Parasitol Res ; 121(2): 623-631, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34985596

RESUMO

Protein phosphorylation plays key roles in a variety of essential cellular processes. Fasciola gigantica is a tropical liver fluke causing hepatobiliary disease fascioliasis, leading to human health threats and heavy economic losses. Although the genome and protein kinases of F. gigantica provided new insights to understand the molecular biology and etiology of this parasite, there is scant knowledge of protein phosphorylation events in F. gigantica. In this study, we characterized the global phosphoproteomics of adult F. gigantica by phosphopeptide enrichment-based LC-MS/MS, a high-throughput analysis to maximize the detection of a large repertoire of phosphoproteins and phosphosites. A total of 1030 phosphopeptides with 1244 phosphosites representing 635 F. gigantica phosphoproteins were identified. The phosphoproteins were involved in a wide variety of biological processes including cellular, metabolic, and single-organism processes. Meanwhile, these proteins were found predominantly in cellular components like membranes and organelles with molecular functions of binding (51.3%) and catalytic activity (40.6%). The KEGG annotation inferred that the most enriched pathways of the phosphoproteins included tight junction, spliceosome, and RNA transport (each one contains 15 identified proteins). Combining the reports in other protozoa and helminths, the phosphoproteins identified in this work play roles in metabolic regulation and signal transduction. To our knowledge, this work performed the first global phosphoproteomics analysis of adult F. gigantica, which provides valuable information for development of intervention strategies for fascioliasis.


Assuntos
Fasciola hepatica , Fasciola , Fasciolíase , Animais , Cromatografia Líquida , Humanos , Espectrometria de Massas em Tandem
11.
J Obstet Gynaecol Res ; 48(11): 2926-2934, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36054651

RESUMO

OBJECTIVE: To review of our hospital's experiences in transvaginal natural orifice transluminal endoscopic surgery (vNOTES) and challenges we encountered in performance of the procedure, so as to provide help to medical institutions who are preparing to carry out vNOTES. METHODS: We retrospectively analyzed the data of all patients receiving vNOTES in our hospital from April 2018 to May 2021. Data we collected cover the general characteristics, perioperative outcomes, and complications of the patients. RESULTS: A total of 1147 patients underwent vNOTES in the past 3 years at our hospital. The total numbers of adnexal surgery, myomectomy, hysterectomy, pelvic floor reconstruction surgery, and malignant tumor surgery performed via vNOTES were 902, 98, 82, 51, and 14, respectively. Eighteen patients were converted to transabdominal laparoscopic surgery. A total of 38 patients had complications according to Clavien-Dindo classification, and the total complication rate was 3.31%. Among these cases of complications, 27 were Grade I, 4 were Grade II, and 7 were Grade III. No complications of Grade IV or V were reported. CONCLUSION: The application of vNOTES is safe and feasible for most gynecological surgeries. Moreover, hospitals with traditional laparoscopic equipment are advised to try this technique as there is no need to purchase additional expensive equipment. However, since vNOTES represents a novel approach, the long-term complications and efficacy associated with this technique are pending to be verified through large-scale prospective multicenter randomized controlled studies.


Assuntos
Laparoscopia , Cirurgia Endoscópica por Orifício Natural , Criança , Feminino , Humanos , Estudos Retrospectivos , Estudos Prospectivos , Cirurgia Endoscópica por Orifício Natural/métodos , Histerectomia/métodos , Laparoscopia/métodos , Hospitais , Vagina/cirurgia
12.
Int J Mol Sci ; 23(3)2022 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-35163816

RESUMO

Zinc finger proteins are widely involved and play an important role in plant growth and abiotic stress. In this research, MdZAT5, a gene encoding C2H2-type zinc finger protein, was cloned and investigated. The MdZAT5 was highly expressed in flower tissues by qRT-PCR analyses and GUS staining. Promoter analysis showed that MdZAT5 contained multiple response elements, and the expression levels of MdZAT5 were induced by various abiotic stress treatments. Overexpression of MdZAT5 in apple calli positively regulated anthocyanin accumulation by activating the expressions of anthocyanin biosynthesis-related genes. Overexpression of MdZAT5 in Arabidopsis also enhanced the accumulation of anthocyanin. In addition, MdZAT5 increased the sensitivity to salt stress in apple calli. Ectopic expression of MdZAT5 in Arabidopsis reduced the expression of salt-stress-related genes (AtNHX1 and AtABI1) and improved the sensitivity to salt stress. In conclusion, these results suggest that MdZAT5 plays a positive regulatory role in anthocyanin accumulation and negatively regulates salt resistance.


Assuntos
Antocianinas/metabolismo , Arabidopsis/crescimento & desenvolvimento , Malus/crescimento & desenvolvimento , Proteínas Repressoras/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Clonagem Molecular , Flores/genética , Flores/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas , Malus/genética , Malus/metabolismo , Modelos Moleculares , Filogenia , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas/metabolismo , Regiões Promotoras Genéticas , Proteínas Repressoras/química , Proteínas Repressoras/genética , Estresse Salino , Regulação para Cima
13.
Int J Mol Sci ; 23(13)2022 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-35806456

RESUMO

Receptor-like kinases (RLKs) are a large group of pattern recognition receptors (PRRs) and play a critical role in recognizing pathogens, transducing defense signals, and mediating the activation of immune defense responses. Although extensively studied in the model plant Arabidopsis, studies of RLKs in crops, including soybean, are limited. When a BAK1-interacting receptor-like kinase (BIR1) homolog (referred to as GmBIR1 hereafter) was silenced by the BPMV (Bean pod mottle virus)-induced gene silencing (BPMV-VIGS), it resulted in phenotypes that were reminiscent of constitutively activated defense responses, including a significantly stunted stature with observable cell death on the leaves of the silenced plants. In addition, both SA and H2O2 were over-accumulated in the leaves of the GmBIR1-silenced plants. Consistent with this autoimmune phenotype, GmBIR1-silenced plants exhibited significantly enhanced resistance to both Pseudomonas syringae pv. glycinea (Psg) and Soybean mosaic virus (SMV), two different types of pathogens, compared to the vector control plants. Together, our results indicated that GmBIR1 is a negative regulator of immunity in soybean and the function of BIR1 homologs is conserved in different plant species.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/fisiologia , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Peróxido de Hidrogênio/metabolismo , Doenças das Plantas , Pseudomonas syringae/fisiologia , Glycine max/fisiologia
14.
J Neuroinflammation ; 18(1): 174, 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34372857

RESUMO

BACKGROUND: Celastrol (cel) was one of the earliest isolated and identified chemical constituents of Tripterygium wilfordii Hook. f. Based on a cel probe (cel-p) that maintained the bioactivity of the parent compound, the targets of cel in cerebral ischemia-reperfusion (I/R) injury were comprehensively analyzed by a quantitative chemical proteomics method. METHODS: We constructed an oxygen-glucose deprivation (OGD) model in primary rat cortical neurons and a middle cerebral artery occlusion (MCAO) model in adult rats to detect the direct binding targets of cel in cerebral I/R. By combining various experimental methods, including tandem mass tag (TMT) labeling, mass spectrometry, and cellular thermal shift assay (CETSA), we revealed the targets to which cel directly bound to exert neuroprotective effects. RESULTS: We found that cel inhibited the proinflammatory activity of high mobility group protein 1 (HMGB1) by directly binding to it and then blocking the binding of HMGB1 to its inflammatory receptors in the microenvironment of ischemia and hypoxia. In addition, cel rescued neurons from OGD injury in vitro and decreased cerebral infarction in vivo by targeting HSP70 and NF-κB p65. CONCLUSION: Cel exhibited neuroprotective and anti-inflammatory effects by targeting HSP70 and NF-κB p65 and directly binding to HMGB1 in cerebral I/R injury.


Assuntos
Proteína HMGB1/metabolismo , Fármacos Neuroprotetores/farmacologia , Triterpenos Pentacíclicos/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Masculino , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Proteoma/metabolismo , Células RAW 264.7 , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais/efeitos dos fármacos
15.
Artigo em Inglês | MEDLINE | ID: mdl-34313582

RESUMO

Thirteen Gram-stain-positive bacterial strains were isolated from Chinese traditional pickle and the gut of honeybee (Apis mellifera). These strains were characterized using a polyphasic taxonomic approach. The data demonstrated that 12 of the 13 strains represented eight novel species belonging to the genera Apilactobacillus, Secundilactobacillus, Levilactobacillus and Lacticaseibacillus; strains HN36-1T, 887-11T, F79-211-2T, 866-3T, 6-5(1)T, 13B17T, 117-1T and ZW152T were designated as the type strains. Based upon the data of polyphasic characterization obtained in the present study, eight novel species, Apilactobacillus nanyangensis sp. nov., Secundilactobacillus hailunensis sp. nov., Secundilactobacillus yichangensis sp. nov., Levilactobacillus andaensis sp. nov., Levilactobacillus wangkuiensis sp. nov., Levilactobacillus lanxiensis sp. nov., Lacticaseibacillus mingshuiensis sp. nov. and Lacticaseibacillus suilingensis sp. nov., are proposed and the type strains are HN36-1T (=JCM 33867T=CCTCC AB 2019385T), 887-11T (=NCIMB 15201T=CCM 8950T=JCM 33864T=CCTCC AB 2018396T), F79-211-2T (=NCIMB 15254T=JCM 33866T=CCTCC AB 2019384T), 866-3T (=JCM 33863T=CCTCC AB 2019383T), 6-5(1)T (=NCIMB 15229T=CCM 8977T=JCM 33564T=CCTCC AB 2019168T), 13B17T (=NCIMB 15230T=CCM 8979T=JCM 33565T=CCTCC AB 2019167T), 117-1T (=NCIMB 15232T=CCM 8980T=JCM 33567T) and ZW152T (=JCM 34363T=CCTCC AB 2020299T=LMG 32143T=CCM 9110T), respectively.


Assuntos
Abelhas/microbiologia , Alimentos Fermentados/microbiologia , Lactobacillaceae/classificação , Filogenia , Animais , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Microbiologia de Alimentos , Genes Bacterianos , Lactobacillaceae/isolamento & purificação , Hibridização de Ácido Nucleico , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
16.
J Cell Mol Med ; 24(6): 3634-3646, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32068341

RESUMO

There are increasing concerns related to the cardiotoxicity of doxorubicin in the clinical setting. Recently, melatonin has been shown to exert a cardioprotective effect in various cardiovascular diseases, including cardiotoxic conditions. In this study, we examined the possible protective effects of melatonin on doxorubicin-induced cardiotoxicity and explored the underlying mechanisms related to this process. We found that in vitro doxorubicin treatment significantly decreased H9c2 cell viability and induced apoptosis as manifested by increased TUNEL-positive cells, down-regulation of anti-apoptotic protein Bcl-2, as well as up-regulation of pro-apoptotic protein Bax. This was associated with increased reactive oxygen species (ROS) levels and decreased mitochondrial membrane potentials (MMP). In vivo, five weeks of doxorubicin treatment significantly decreased cardiac function, as evaluated by echocardiography. TUNEL staining results confirmed the increased apoptosis caused by doxorubicin. On the other hand, combinational treatment of doxorubicin with melatonin decreased cardiomyocyte ROS and apoptosis levels, along with increasing MMP. Such doxorubicin-melatonin co-treatment alleviated in vivo doxorubicin-induced cardiac injury. Western Blots, along with in vitro immunofluorescence and in vivo immunohistochemical staining confirmed that doxorubicin treatment significantly down-regulated Yes-associated protein (YAP) expression, while YAP levels were maintained under co-treatment of doxorubicin and melatonin. YAP inhibition by siRNA abolished the protective effects of melatonin on doxorubicin-treated cardiomyocytes, with reversed ROS level and apoptosis. Our findings suggested that melatonin treatment attenuated doxorubicin-induced cardiotoxicity through preserving YAP levels, which in turn decreases oxidative stress and apoptosis.


Assuntos
Cardiotoxicidade/tratamento farmacológico , Doxorrubicina/efeitos adversos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Melatonina/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Cardiotônicos/farmacologia , Morte Celular/efeitos dos fármacos , Linhagem Celular , Regulação para Baixo/efeitos dos fármacos , Masculino , Melatonina/farmacologia , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Miocárdio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Proteínas de Sinalização YAP
17.
Int J Syst Evol Microbiol ; 70(12): 6414-6417, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33112225

RESUMO

Recently, the members of the genus Lactobacillus have been reclassified by Zheng et al. At the same time, Lactobacillus buchneri subsp. silagei, Lactobacillus zhaodongensis, Lactobacillus argentoratensis and Lactobacillus zeae have been successively and validly published, and Lactobacillus kosoi has also been reclassified. In the present study, all these species and subspecies were re-evaluated by 16S rRNA gene sequence analysis or a combination of 16S rRNA gene sequence analysis and phylogenomic treeing. On the basis of the results presented here, we propose to reclassify Lactobacillus zhaodongensis, Lactobacillus zeae, Lactobacillus argentoratensis and Lactobacillus buchneri subsp. silagei as Lacticaseibacillus zhaodongensis comb. nov., Lacticaseibacillus zeae comb. nov., Lactiplantibacillus argentoratensis comb. nov. and Lentilactobacillus buchneri subsp. silagei comb. nov., respectively and Apilactobacillus kosoi as a later heterotypic synonym of Apilactobacillus micheneri.


Assuntos
Filogenia , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genética , Lactobacillus/classificação , Análise de Sequência de DNA
18.
Int J Syst Evol Microbiol ; 70(5): 3123-3133, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32250238

RESUMO

Lactobacillus kosoi Chiou et al. 2018 and Lactobacillus micheneri McFrederick et al. 2018 are closely related, and they share 100 % 16S rRNA gene sequence similarity, 99.6 % pheS gene sequence similarity, 100 % rpoA gene sequence similarity, 97.3 % average nucleotide identity (ANI) value and 76.6 % in silico DNA-DNA hybridization (isDDH) value, indicating that they represent the same species. Fatty acid methyl esters (FAME) analysis and phenotypic characterization also indicated that L. kosoi and L. micheneri are very similar. We propose L. kosoi Chiou et al. 2018 as a later heterotypic synonym of L. micheneri McFrederick et al. 2018. The taxonomic position of Lactobacillus plantarum subsp. argentoratensis in the L. plantarum group was re-examined using a polyphasic approach, including sequence analyses of 16S rRNA, pheS, rpoA and recA genes, average nucleotide identity analysis, in silico DNA-DNA hybridization, fatty acid methyl ester analysis and phenotypic characterization. Results of 16S rRNA gene sequence analysis indicated that L. plantarum subsp. argentoratensis was closely related to L. plantarum subsp. plantarum, L. pentosus and L. paraplantarum in the L. plantarum group, sharing 99.6-99.7 % 16S rRNA gene sequence similarities. Results of pheS, rpoA and recA gene sequence analyses indicated that L. plantarum subsp. argentoratensis was most closely related to L. plantarum subsp. plantarum, having 91.8 % pheS gene sequence similarity, 98.9 % rpoA gene sequence similarity and 93.1 % recA gene sequence similarity. L. plantarum subsp. argentoratensis DSM 16365T shared 95.6 % ANI value and 62.9 % isDDH value with L. plantarum subsp. plantarum ATCC 14917T. The low isDDH value confirmed that L. plantarum subsp. argentoratensis and L. plantarum subsp. plantarum represent two different species, rather than two different subspecies in the L. plantarum group. On the basis of the data from polyphasic characterization obtained in the present study and in previous studies, L. plantarum subsp. argentoratensis is elevated to the species level and represents a novel species of the genus Lactobacillus, for which the name Lactobacillus argentoratensis sp. nov. is proposed and the type strain is DKO 22T (=CIP 108320T=DSM 16365T=JCM 16169T). Two novel Gram-stain-positive bacterial strains, designated 1206-1T and F027-1-2, were isolated from traditional pickle in Heilongjiang Province, PR China, and from the intestinal tract of a honey bee (Apis mellifera) in Hubei Province, PR China, respectively. The two bacteria were characterized by a polyphasic approach, including 16S rRNA gene sequence analysis, pheS gene sequence analysis, rpoA gene sequence analysis, fatty acid methyl ester analysis, average nucleotide identity analysis, in silico DNA-DNA hybridization analysis and an analysis of phenotypic features. The results of 16S rRNA gene sequence analysis indicated that strains 1206-1T and F027-1-2 were distantly related to Lactobacillus sharpeae, Lactobacillus hulanensis, Lactobacillus songhuajiangensis, Lactobacillus pantheris, Lactobacillus thailandensis, Lactobacillus camelliae, Lactobacillus jixianensis, Lactobacillus nasuensis, Lactobacillus baoqingensis, Lactobacillus manihotivorans and Lactobacillus porcinae. Strain 1206-1T exhibited 94.2-96.4 % 16S rRNA gene sequence similarities, 69.5-83.3 % pheS gene sequence similarities and 73.1-90.3 % rpoA gene sequence similarities to type strains of phylogenetically related species. ANI and isDDH values between strain 1206-1T and the type strains of phylogenetically related species were 52.7-73.7 % and 21.1-30.1 %, respectively. On the basis of the data obtained in the present study, a novel species, Lactobacillus zhaodongensis sp. nov. is proposed and the type strain is 1206-1T (=CCM 8981T=CCTCC AB 2019200T=LMG 31620T).


Assuntos
Abelhas/microbiologia , Alimentos Fermentados/microbiologia , Microbiologia de Alimentos , Lactobacillus/classificação , Filogenia , Animais , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Trato Gastrointestinal/microbiologia , Genes Bacterianos , Lactobacillus/isolamento & purificação , Lactobacillus plantarum/classificação , Hibridização de Ácido Nucleico , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
19.
Int J Syst Evol Microbiol ; 70(11): 5964-5968, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32960752

RESUMO

In 2018, Nouioui et al. transferred Bifidobacterium gallinarum and Bifidobacterium saeculare to Bifidobacterium pullorum as B. pullorum subsp. gallinarum and B. pullorum subsp. saeculare on the basis of digital DNA-DNA hybridization (dDDH) values. These two new subspecies were validated in the same year. However, we found that the genome (GenBank/ENA/DDBJ accession number JGZJ01000000) of B. pullorum used by Nouioui et al. in the dDDH analysis cannot represent B. pullorum. So, the taxonomic relationship between B. gallinarum, B. saeculare and B. pullorum should be re-examined. B. pullorum DSM 20433T had 88.7-89.0 % average nucleotide identity (ANI) values and 37.5-38.0 % dDDH values to the type strains of B. gallinarum and B. saeculare, respectively, less than the threshold for species demarcation, confirming that B. pullorum represents a different species from B. gallinarum and B. saeculare. The ANI values and dDDH values between the type strains of B. gallinarum and B. saeculare were 96.7-96.9 % and 73.0-73.3 %, respectively, greater than the threshold for species demarcation, confirming that they represent the same species. Relatively low dDDH values (less than the 79-80 % threshold for subspecies demarcation) between the type strains of B. gallinarum and B. saeculare indicated that B. saeculare can be considered as a subspecies of B. gallinarum. On the basis of the results presented here, (i) B. gallinarum and B. saeculare should not be transferred to B. pullorum; (ii) we propose B. saeculare Biavati et al. 1992 as a later heterotypic synonym of B. gallinarum Watabe et al. 1983 and as a new subspecies of B. gallinarum, for which the name B. gallinarum subsp. saeculare subsp. nov. is proposed.


Assuntos
Bifidobacterium/classificação , Filogenia , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Hibridização de Ácido Nucleico , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
20.
Inorg Chem ; 59(5): 2952-2960, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32045221

RESUMO

Due to the intrinsic coordination preference of the linear uranyl unit, uranyl-organic frameworks (UOFs) are generally prone to exhibiting low-dimensional structures. Reactions of uranyl nitrate with biphenyl-3,3'-disulfonyl-4,4'-dicarboxylic acid dipotassium salt (K2H2BPDSDC) under different conditions led to three UOFs, namely, {(Me2NH2)[K2(UO2)3(µ3-O)(µ3-OH)2(µ2-OH)(BPDSDC)(H2O)3]·4DMF}n (1), {[K2(UO2)(µ3-O)(BPDSDC)0.5(H2O)2]}n (2), and {(Me2NH2)2.5[K1.5(UO2)(BPDSDC)1.5(H2O)3]}n (3). Compounds 1 and 2 contain one-dimensional (1D) ribbon structures formed from UO22+ units bridged by µ3-O atoms and carboxylate groups. The 1D ribbons in 1 are linked by K+ atoms to form a two-dimensional (2D) layer, which is further pillared by the biphenyl units to give a three-dimensional (3D) framework. For 2, the oxygen atoms of UO22+ units in each 1D ribbon bridge the K+ atoms to form four -[K-O-K]n- infinite chains located above and below the ribbon. The 1D ribbons in 2 are bridged by sulfonate groups to generate a 3D substructure featuring 1D channels occupied by biphenyl moieties. In 3, each mononuclear [(UO2)(COO)3] unit is bridged by three K+ atoms to form a 3D substructure featuring 1D small left-handed and large righted helical channels occluded by biphenyl moieties. Compound 2 exhibits an excellent proton conductivity with the highest conductivity of 1.07 × 10-3 S cm-1. The inner walls of 1D channels of 2 are full of the hydrophilic sulfonate groups, which boost enrichment of the guest water molecules, thus resulting in a high proton conductivity. Finally, temperature dependence of fluorescent studies showed that compounds 1 and 2 display the characteristic uranyl emissions. This work presents the elegant examples of the rarely explored 3D UOFs and expands the potentials of UOFs.

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