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BACKGROUND: Wogonin (5, 7-dihydroxy-8-methoxyflavone) is a natural di-hydroxyl flavonoid extracted from the root of Scutellaria baicalensis Georgi. This paper was intended to investigate the mechanism of action of wogonin in alleviating the inflammation and apoptosis in acute lung injury (ALI). MATERIALS AND METHODS: Lipopolysaccharide (LPS) was used to establish the in vitro model of ALI. After wogonin treatment, the cell viability and apoptosis of LPS-induced A549 cells were, respectively, measured by CCK-8, TUNEL assays and acridine orange/ethidium bromide dual staining, while the contents of inflammatory cytokines and oxidative stress markers were estimated by RT-qPCR, ELISA assay, western blot analysis and commercial kits. Western blot was also conducted to assess the expression of proteins involved. Subsequently, the effect of wogonin on the sirtuin 1 (SIRT1)-mediated high-mobility group box 1 protein (HMGB1) deacetylation was investigated. SIRT1 inhibitor EX527 was used to evaluate the regulatory effects of wogonin on SIRT1-mediated HMGB1 deacetylation in A549 cells under LPS stimulation. RESULTS: LPS induced inflammation, oxidative stress and apoptosis of A549 cells, which was abolished by wogonin. It was also found that wogonin promoted the HMGB1 deacetylation, accompanied by upregulated SIRT1 expression. However, SIRT1 inhibitor EX527 partially reversed the protective effects of wogonin on the inflammation and apoptosis of LPS-induced A549 cells. CONCLUSION: Wogonin alleviated the inflammation and apoptosis in LPS-induced A549 cells by SIRT1-mediated HMGB1 deacetylation, which might represent the identification of a novel mechanism by which wogonin exerts protective effects on ALI and provide ideas for the application of wogonin to ALI treatment.
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Inflamação , Lipopolissacarídeos , Apoptose , Células Epiteliais , Flavanonas , Humanos , Lipopolissacarídeos/toxicidade , PulmãoRESUMO
Sepsis-induced acute lung injury is a common and severe complication of sepsis, for which effective treatments are currently lacking. Previous studies have demonstrated the influence of wogonin in treating acute lung injury (ALI). However, its precise mechanism of action remains unclear. To delve deeper into the mechanisms underlying wogonin's impacts in sepsis-induced acute lung injury, we established a mouse sepsis model through cecal ligation and puncture and conducted further cell experiments using lipopolysaccharide-treated MH-S and MLE-12 cells to explore wogonin's potential mechanisms of action in treating ALI. Our results revealed that wogonin significantly increased the survival rate of mice, alleviated pulmonary pathological damage and inflammatory cell infiltration, and activated the SIRT1-FOXO1 pathway. Additionally, wogonin suppressed the release of pro-inflammatory factors by M1 macrophages and induced the activation of M2 anti-inflammatory factors. Further in vitro studies confirmed that wogonin effectively inhibited M1 macrophage polarization through the activation of the SIRT1-FOXO1 pathway, thereby mitigating lung pathological changes caused by ALI. In summary, our study demonstrated that wogonin regulated macrophage M1/M2 polarization through the activation of the SIRT1-FOXO1 pathway, thereby attenuating the inflammatory response and improving pulmonary pathological changes induced by sepsis-induced ALI. This discovery provided a solid mechanistic foundation for the therapeutic use of wogonin in sepsis-induced ALI, shedding new light on potential strategies for the treatment of sepsis-induced ALI.
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Lesão Pulmonar Aguda , Flavanonas , Proteína Forkhead Box O1 , Macrófagos , Sepse , Transdução de Sinais , Sirtuína 1 , Animais , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/patologia , Sirtuína 1/metabolismo , Sepse/complicações , Sepse/tratamento farmacológico , Sepse/metabolismo , Flavanonas/farmacologia , Camundongos , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Proteína Forkhead Box O1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Polaridade Celular/efeitos dos fármacos , Ativação de Macrófagos/efeitos dos fármacosRESUMO
Dietary strategies rich in fiber have been demonstrated to offer benefits to individuals afflicted with rheumatoid arthritis (RA). However, the specific mechanisms through which a high-fiber diet (HFD) mitigates RA's autoimmunity remain elusive. Herein, we investigate the influence of pectin- and inulin-rich HFD on collagen-induced arthritis (CIA). We establish that HFD significantly alleviates arthritis in CIA mice by regulating the Th17/Treg balance. The rectification of aberrant T cell differentiation by the HFD is linked to the modulation of gut microbiota, augmenting the abundance of butyrate in feces. Concurrently, adding butyrate to the drinking water mirrors the HFD's impact on ameliorating CIA, encompassing arthritis mitigation, regulating intestinal barrier integrity, and restoring the Th17/Treg equilibrium. Butyrate reshapes the metabolic profile of CD4+ T cells in an AMPK-dependent manner. Our research underscores the importance of dietary interventions in rectifying gut microbiota for RA management and offers an explanation of how diet-derived microbial metabolites influence RA's immune-inflammatory-reaction.
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The multifunctional protein staphylococcal nuclease domain-containing protein 1 (SND1) is conserved and has been implicated in several aspects of tumor development, such as proliferation, epithelial-mesenchymal transition, and immune evasion. Despite this, the precise role of SND1 in the initiation and metastasis of mammary gland tumors remains largely unexplored. In this study, we utilized a mouse model of breast tumors induced by polyomavirus middle T antigen (PyMT) to demonstrate that the knockout of SND1 significantly delayed the onset of primary mammary tumor formation induced by PyMT. Histological staining and cytometric analysis were conducted to confirm the reduction of tumor-initiating cells and lung metastasis following depletion of SND1. Additionally, our findings demonstrate that enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), a crucial epigenetic modifier implicated in PyMT-induced breast tumors, serves as an essential mediator of SND1-promoted primary mammary tumor formation. Mechanistic investigations revealed that SND1 functions as a transcriptional co-activator of hypoxia-inducible factor 1 subunit alpha (HIF1α), thereby regulating the downstream target gene EZH2 and promoting tumorigenesis. Overall, this study provides novel insights into the role of SND1 as a co-activator of HIF1α in the acceleration of PyMT-induced spontaneous breast tumor formation through the promotion of EZH2 transcription. The findings provide novel insights into the relationship between SND1 and the formation of tumor-initiating cells.
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Neoplasias da Mama , Endonucleases , Neoplasias Pulmonares , Animais , Feminino , Humanos , Camundongos , Antígenos Virais de Tumores , Neoplasias da Mama/genética , Transformação Celular Neoplásica , Endonucleases/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Pulmonares/metabolismo , Fatores de Transcrição/genéticaRESUMO
Acuticoccus sp. I52.16.1 was isolated from 100 m water depth from the Indian Ocean, and presented a novel Acuticoccus species belonging to the family Acuticoccaceae, class Alphaproteobacteria. The strain I52.16.1 displayed the activities of nitrate reductase, nitrite reductase, and urease. The genome of Acuticoccus sp. I52.16.1 consisted of a circular chromosome (5, 134, 086bp) with a G + C content of 69.7 mol%. The predicted number of coding genes was 4935, including 6 rRNA, 47 tRNA, and 2 sRNA. The 16S rDNA sequence displayed the maximum similarity of 97.58% with Acuticoccus yangtzensis JL1095T, followed by Acuticoccus sediminis PTG4-2T (97.05%), Acuticoccus kandeliae J103T (96.52%), and Acuticoccus mangrove B2012T (95.85%). Acuticoccus sp. I52.16.1 contained clades of genes involved in assimilating ammonium, nitrate, nitrite, and simple organic nitrogen compounds, but lacked the pathway for dissimilatory denitrification. Two distinct types of ureases were also detected, suggesting genetic heterogeneity. This study provided insight into the nitrogen metabolism strategies of heterotrophic bacteria in the oligotrophic ocean surface.
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Nitrogênio , Água , Composição de Bases , Oceano Índico , Nitrogênio/metabolismo , Sequenciamento Completo do GenomaRESUMO
AIM: This study was conducted to increase knowledge on the actuality of resilience, social support and quality of life among inflammatory bowel disease patients in China to provide evidence for psychological support. DESIGN: Using convenience sampling, 249 outpatients and inpatients with inflammatory bowel disease from a hospital who completed the questionnaires were enrolled in the analytic questionnaire-based study. METHODS: Demographic information forms, Resilience Scale for Inflammatory Bowel Disease, Social Support Rating Scale and Short Health Scale were administered. RESULTS: It was found that the resilience of patients with inflammatory bowel disease should be enhanced. When considering factors that influence resilience, the place of residence (living in rural areas) and utilization of social support should be considered. Resilience demonstrated a positive correlation with utilization of social support, and different place of residence was related to resilience. Targeted interventions should be implemented to increase patients' resilience and quality of life.
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Doenças Inflamatórias Intestinais , Qualidade de Vida , China , Doença Crônica , Estudos Transversais , Humanos , Doenças Inflamatórias Intestinais/psicologia , Qualidade de Vida/psicologia , Apoio SocialRESUMO
The diffusion of ferric ions is an important challenge to limit the application of Fricke gel dosimeters in accurate three-dimensional dose verification of modern radiotherapy. In this work, low-diffusion Fricke gel dosimeters, with a core-shell structure based on spatial confinement, were constructed by utilizing microdroplet ultrarapid freezing and coating technology. Polydimethylsiloxane (PDMS), with its excellent hydrophobicity, was coated on the surface of the pellets. The concentration gradient of the ferric ion was realized through shielding half of a Co-60 photon beam field size, and ion diffusion was measured by both ultraviolet-visible spectrophotometry and magnetic resonance imaging. No diffusion occurred between the core-shell pellets, even at 96 h after irradiation, and the diffusion length at the irradiation boundary was limited to the diameter (2-3 mm) of the pellets. Furthermore, Monte Carlo calculations were conducted to study dosimetric properties of the core-shell dosimeter, which indicated that a PDMS shell hardly affected the performance of the dosimeter.
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Most sheep breeding programs designed for the tropics and sub-tropics have to take into account the impacts of environmental adaptive traits. However, the genetic mechanism regulating the multiple biological processes driving adaptive responses remains unclear. In this study, we applied a selective sweep analysis by combing 1% top values of Fst and ZHp on both altitude and geographic subpopulations (APS) in 636 indigenous Tibetan sheep breeds. Results show that 37 genes were identified within overlapped genomic regions regarding Fst significantly associated with APS. Out of the 37 genes, we found that 8, 3 and 6 genes at chromosomes (chr.) 13, 23 and 27, respectively, were identified in the genomic regions with 1% top values of ZHp. We further analyzed the INDEL variation of 6 genes at chr.27 (X chromosome) in APS together with corresponding orthologs of 6 genes in Capra, Pantholops, and Bos Taurus. We found that an INDEL was located within 5'UTR region of HAG1 gene. This INDEL of HAG1 was strongly associated with the variation of APS, which was further confirmed by qPCR. Sheep breeds carrying "C-INDEL" of HAG1 have significantly greater body weight, shear amount, corpuscular hemoglobin and globulin levels, but lower body height, than those carrying "CA-INDEL" of HAG1. We concluded that "C-INDEL" variation of HAG1 gene confers better hypoxia tolerance in the highlands of Tibetan and explains well geographic distributions in this population. These results contribute to our understanding of adaptive responses to altitude and geographic adaptation in Tibetan sheep populations and will help to guide future conservation programs for Tibetan sheep native to Qinghai-Tibetan Plateau.
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Adaptação Fisiológica/genética , Altitude , Ovinos/genética , Animais , Mapeamento Cromossômico , DNA/genética , DNA/isolamento & purificação , Genes/genética , Genética Populacional , Estudo de Associação Genômica Ampla/veterinária , Haplótipos/genética , Polimorfismo de Nucleotídeo Único/genética , Alinhamento de Sequência , Análise de Sequência de DNA , Ovinos/anatomia & histologia , Ovinos/fisiologia , TibetRESUMO
In the presence of O(3), the oxidative decolorization reaction on molasses fermentation wastewater with SnO(2) as a catalyst was studied. The results showed that SnO(2) accelerated the ozone oxidation reaction and the oxidative decolorization of molasses fermentation wastewater was accelerated. Influences on SnO(2) catalytic ozonation activity by precipitants and the calcination temperature were studied by XRD, IR and TG-DSC. SnO(2) prepared by ammonia as the precipitant had higher catalytic activity and a stronger dehydroxylation. The IR spectra of adsorbed pyridine showed that there were Lewis acid sites on the surface of this SnO(2) catalyst. The main factors influencing molasses fermentation wastewater oxidative decolorization were the wastewater concentration, the O(3) concentration, the pH value and the catalyst dosage. The decolorization of wastewater was improved with the increase of the wastewater dilution ratio, the ozone concentration and the catalyst dosage. High activity *OH was found to be existing with less amount and low concentration in the process of SnO(2) catalyzed ozonation decolorization.
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Fermentação , Melaço , Ozônio/química , Compostos de Estanho/química , Poluentes da Água/química , Adsorção , Varredura Diferencial de Calorimetria , Catálise , Cor , Concentração de Íons de Hidrogênio , Difração de Raios XRESUMO
SnO2 was prepared by precipitation method and mental oxides modified SnO2 catalysts were prepared by coprecipitation method. High concentration molasses fermentation wastewater degradation by SnO2 catalyzed ozonation was used as a probe reaction and IR spectra were used to study the adsorption of O3 at SnO2 and different metal oxides modification SnO2 surface. The results showed, that in the infrared absorption spectra of adsorption of O3 prepared by pure O2 at SnO2 catalyst surface, two obvious bidentate absorption double peaks were found at 1 027 and 1 055 cm(-1), and 2 099 and 2 122 cm(-1), respectively. However, there was competitive adsorption between O3 prepared by air, and CO and CO2. Then the O3 adsorption decreased, leading to the decrease in the degradation of molasses fermentation wastewater by SnO2 catalytic ozonation, and after 60 min reaction, the degradation rate by pure oxygen as oxygen source was 79.2%. It was 33.1% more by air as oxygen source. Similar strength adsorption peaks in the infrared spectra were found at 2 236, 2213 cm(-1) and 1 628, 1 599 cm (-1) with Fe2O3, NiO, CuO, ZnO, MgO, SrO and BaO modified SnO2. But the adsorption of CO2 and CO was different on modifier-SnO2, There was a wide absorption peak at 1 580-1 070 cm(-1) in the infrared spectra of transition metal modified SnO2, and two new peaks at 1 298 and 1 274 cm(-1) were found between 1 580 and 1 070 cm(-1) in the infrared spectra of alkaline-earth metals modified SnO2 catalysts. These changes leaded to a different catalytic ozonation activity of modifier-SnO2, the results of molasses fermentation wastewater degradation by ozone combined with alkaline-earth metal modified SnO2 was obviously better than ozone combined with transition metal modified SnO2. And among them, the ozonation catalytic activity of BaO-SnO2 was the best.
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Ozônio/química , Compostos de Estanho/química , Eliminação de Resíduos Líquidos/métodos , Purificação da Água/métodos , Adsorção , Catálise , Fermentação , MelaçoRESUMO
The molecular and population genetic evidence of the phylogenetic status of the Tibetan sheep (Ovis aries) is not well understood, and little is known about this species' genetic diversity. This knowledge gap is partly due to the difficulty of sample collection. This is the first work to address this question. Here, the genetic diversity and phylogenetic relationship of 636 individual Tibetan sheep from fifteen populations were assessed using 642 complete sequences of the mitochondrial DNA D-loop. Samples were collected from the Qinghai-Tibetan Plateau area in China, and reference data were obtained from the six reference breed sequences available in GenBank. The length of the sequences varied considerably, between 1031 and 1259 bp. The haplotype diversity and nucleotide diversity were 0.992±0.010 and 0.019±0.001, respectively. The average number of nucleotide differences was 19.635. The mean nucleotide composition of the 350 haplotypes was 32.961% A, 29.708% T, 22.892% C, 14.439% G, 62.669% A+T, and 37.331% G+C. Phylogenetic analysis showed that all four previously defined haplogroups (A, B, C, and D) were found in the 636 individuals of the fifteen Tibetan sheep populations but that only the D haplogroup was found in Linzhou sheep. Further, the clustering analysis divided the fifteen Tibetan sheep populations into at least two clusters. The estimation of the demographic parameters from the mismatch analyses showed that haplogroups A, B, and C had at least one demographic expansion in Tibetan sheep. These results contribute to the knowledge of Tibetan sheep populations and will help inform future conservation programs about the Tibetan sheep native to the Qinghai-Tibetan Plateau.
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DNA Mitocondrial/genética , Evolução Molecular , Filogenia , Ovinos/genética , Animais , Polimorfismo Genético , Ovinos/classificação , TibetRESUMO
OBJECTIVE: To explore the therapeutic efficacy of patients with ulcerative colitis (UC) treated by retention enema and per-colonoscopic spraying of Zhikang Compound Liquid (ZKCL). METHODS: Eighty-six patients with UC were divided into two groups. The 52 patients in the treated group were treated for 4 courses of retention enema, the drug for enema used in the 1st course was ZKCL-A (consisted of normal saline, Zhikang capsule, gentamycin and dexamethasone) and smecta, in the 2nd course ZKCL-A alone, in the 3rd and 4th course, ZKCL-B (with the same contents of ZKCL-A but without dexamethasone), the enema was carried out once a day in the evening, 15 days as one course. Besides, local spraying of ZKCL-A and smecta were given once by colonoscopy before the 1st and 3rd course. The 34 patients in the control group were treated by salicylazosulfapyridine orally. RESULTS: In the treated group, 32 patients got complete remitted, 15 were treated effectively, 5 ineffectively, the total effective rate being 90.38% while the corresponding number in the control group were 8, 14, 12, and 64.71%, respectively. Significant difference was seen when compared with the therapeutic effects of the two groups. CONCLUSION Good efficacy was got in treating patients with UC by retention enema and per-colonoscopic spraying with ZKCL.