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1.
Neural Regen Res ; 18(3): 643-651, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36018189

RESUMO

TMEM16F is involved in many physiological processes such as blood coagulation, cell membrane fusion and bone mineralization. Activation of TMEM16F has been studied in various central nervous system diseases. High TMEM16F level has been also found to participate in microglial phagocytosis and transformation. Microglia-mediated neuroinflammation is a key factor in promoting the progression of Alzheimer's disease. However, few studies have examined the effects of TMEM16F on neuroinflammation in Alzheimer's disease. In this study, we established TMEM16F-knockdown AD model in vitro and in vivo to investigate the underlying regulatory mechanism about TMEM16F-mediated neuroinflammation in AD. We performed a Morris water maze test to evaluate the spatial memory ability of animals and detected markers for the microglia M1/M2 phenotype and NLRP3 inflammasome. Our results showed that TMEM16F was elevated in 9-month-old APP/PS1 mice. After TMEM16F knockdown in mice, spatial memory ability was improved, microglia polarization to the M2 phenotype was promoted, NLRP3 inflammasome activation was inhibited, cell apoptosis and Aß plaque deposition in brain tissue were reduced, and brain injury was alleviated. We used amyloid-beta (Aß25-35) to stimulate human microglia to construct microglia models of Alzheimer's disease. The levels of TMEM16F, inducible nitric oxide synthase (iNOS), proinflammatory cytokines and NLRP3 inflammasome-associated biomarkers were higher in Aß25-35 treated group compared with that in the control group. TMEM16F knockdown enhanced the expression of the M2 phenotype biomarkers Arg1 and Socs3, reduced the release of proinflammatory factors interleukin-1, interleukin-6 and tumor necrosis factor-α, and inhibited NLRP3 inflammasome activation through reducing downstream proinflammatory factors interleukin-1ß and interleukin-18. This inhibitory effect of TMEM16F knockdown on M1 microglia was partially reversed by the NLRP3 agonist Nigericin. Our findings suggest that TMEM16F participates in neuroinflammation in Alzheimer's disease through participating in polarization of microglia and activation of the NLRP3 inflammasome. These results indicate that TMEM16F inhibition may be a potential therapeutic approach for Alzheimer's disease treatment.

2.
J Ethnopharmacol ; 300: 115741, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36162543

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Pulsatilla decoction (PD), is an herbal formula commonly used for the treatment of ulcerative colitis (UC) in clinical practice, but the mechanism of PD alters the colitis remains elusive. AIM OF THE STUDY: To evaluate the intervention effect of PD on Dextran Sodium Sulfate (DSS)-induced UC based on gut microbiota and intestinal short-chain fatty acid (SCFAs) metabolism, and to investigate the mechanism of action of PD in treating UC. MATERIALS AND METHODS: A 3% (wt/vol) DSS-induced ulcerative colitis model in C57BL/6 male mice was used to evaluate the effect of oral PD in treating UC. The changes in gut microbiota in mice were analyzed by 16SrDNA gene sequencing, and the content of SCFAs in the intestinal contents of mice was determined by gas chromatography-mass spectrometry (GC-MS). Enzyme-linked immunosorbent assay (ELISA) was applied to analyze the expression of inflammatory cytokines in serum and colonic tissues, and western blotting (WB) was applied to analyze the expression of tight junction proteins in colonic tissues. RESULTS: PD can alleviate the symptoms of UC mice, Pulsatilla Decoction high dose treatment group (PDHT) shows the best effect. Compared with the DSS group, the PDHT had significantly lower body mass, disease activity index (DAI) score, colonic macroscopic damage index (CMDI) score, and pathological damage score, at the phylum level, the relative abundance of Bacteroidetes increased while that of Firmicutes and Proteobacteria decreased, at the Genus level, the abundance of Bacteroides and Lachnospiraceae.NK4A136.group increased while that of Clostridium. sensu.stricto。, Escherichia. shigella and Turicibacter decreased. Compared with the DSS group, acetate, propionate, and total SCFAs in the PDHT with significantly higher levels. The concentrations of interleukin-1ß (L-1ß), tumor necrosis factor-alpha (TNF-α), and interleukin-17 (IL-17) decreased whereby the concentration of interleukin-10 (IL-10) increased in the PDHT group. The expression levels of Occludin, zonula occludens-1 (ZO-1), Claudin1, Claudin5, G protein-coupled receptor43 (GPR43) protein, and the relative expression of ZO-1 and Occludin mRNA were significantly increased PDHT group. CONCLUSIONS: PD has a good therapeutic effect on UC mice. The pharmacological mechanism is probably maintaining the homeostasis and diversity of gut microbiota, increasing the content of SCFAs, and repairing the colonic mucosal barrier.


Assuntos
Colite Ulcerativa , Colite , Pulsatilla , Animais , Bactérias/metabolismo , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colo , Citocinas/metabolismo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Ácidos Graxos Voláteis/metabolismo , Interleucina-10/metabolismo , Interleucina-17/metabolismo , Interleucina-1beta/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ocludina/metabolismo , Propionatos , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
3.
J Environ Manage ; 325(Pt A): 116510, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36265230

RESUMO

Both microplastic and biofilm are contamination sources in drinking water, but their integrated impacts on water quality have been rarely studied, especially in drinking water distribution pipes with complex hydraulic conditions. This study explored the impacts of hydraulic conditions (0-2 m/s) on microplastic biofilm (MP-BM) development, shear stresses distribution, and microbial community structures. The research was conducted for two weeks using a pilot test device to simulate practical water pipes. The following were the primary conclusions: (1) According to morphology analysis, clusters (>5 µm) significantly increased in the plastisphere when the flow velocity ranged from 0.55 m/s to 0.95 m/s, and average size of clusters decreased when the flow velocity ranged from 1.14 m/s to 1.40 m/s (2) Characteristics of MP-BM impact shear stress on both plastisphere and pipe wall biofilm. Shear stresses were positively correlated with flow velocity, number of MP-BM, and size of MP-BM, while negatively correlated with diameters of pipes. (3) 31 genera changed strictly and monotonously with the fluid velocity, accounting for 15.42%. Opportunistic pathogens in MP-BM such as Sediminibacterium, Curvibacter, and Flavobacterium were more sensitive to hydraulic conditions. Moreover, microplastics (<100 µm) deserve more attention to avoid human ingestion and to prevent mechanical damage and bio-chemical risks.


Assuntos
Água Potável , Microbiota , Humanos , Microplásticos , Plásticos , Biofilmes
4.
Sci Total Environ ; 857(Pt 2): 159371, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36240920

RESUMO

Atmospheric amines have unique acid-neutralizing capacity and play an important role in atmospheric chemical reactions. An integrated observation of PM2.5 samples (from Dec 2015 to Nov 15, 2016) was conducted in a typical industrial city (Xuzhou), China. Concentrations of total measured amines (∑amines, including methylamine (MA), ethylamine (EA), dimethylamine (DMA), propanamine (PA) and trimethylamine (TMA) + diethylamine (DEA)) were 172.0 ± 98.2 ng m-3, accounting 1.5 ± 0.6 ‰ of PM2.5 mass. ∑amines were higher in winter (249.0 ± 112.3 ng m-3) and spring (192.4 ± 75.9 ng m-3) than in summer (114.7 ± 33.3 ng m-3) and autumn (103.7 ± 34.3 ng m-3). Concentrations of MA and EA (the dominant amines) were highest in winter, while DMA, PA and TMA + DEA showed opposite seasonality. EA/MA ratios ranged from 0.04 to 8.7 with a median value of 0.3, and the averaged EA/MA ratio was 2.0 in winter, indicating large contribution of EA. Environmental factors including temperature (T), relative humidity (RH) and atmospheric oxidizing capacity (O3 and Ox represented) were found to influence concentrations of amines in PM2.5. The Positive Matrix Factorization (PMF) model identified secondary products (41.6 %), combustion emissions (39.8 %), soil and waste incineration emissions (13.2 %) and biological emissions and aging products (5.4 %) as the 4 sources of amines in PM2.5. MA was mainly secondary products (82.5 %) and had high contribution of local secondary formation, while EA was mainly derived from combustion emissions (83.7 %) and influenced by regional transportation. In winter, combustion emissions (including coal combustion, biomass burning and traffic emissions, contributed 57.7 %) surpassed secondary products (31.6 %) as the predominant sources of amines, especially under the influence of regional transportation (75.7 %).


Assuntos
Poluentes Atmosféricos , Material Particulado , Material Particulado/análise , Estações do Ano , Poluentes Atmosféricos/análise , Monitoramento Ambiental , Aminas , China , Emissões de Veículos/análise , Aerossóis/análise
6.
J Hazard Mater ; 443(Pt B): 130319, 2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36356521

RESUMO

The present study aimed to investigate the catalytic degradation produced by laccase in the detoxification of glyphosate, isoproturon, lignin polymer, and parathion. We explored laccase-glyphosate, laccase-lignin polymer, laccase-isoproturon, and laccase-parathion using molecular docking (MD) and molecular dynamics simulation (MDS) approaches. The results suggest that laccase interacts well with glyphosate, lignin polymer, isoproturon, and parathion during biodegradation. We calculated the root mean square deviations (RMSD) of laccase-glyphosate, laccase-lignin polymer, laccase-isoproturon, and laccase-parathion as 0.24 ± 0.02, 0.59 ± 0.32, 0.43 ± 0.07, and 0.43 ± 0.06 nm, respectively. In an aqueous solution, the stability of laccase with glyphosate, lignin polymer, isoproturon, and parathion is mediated through the formation of hydrophobic interactions, hydrogen bonds, and van der Waals interactions. The presence of xenobiotic toxic compounds in the active site changed the conformation of laccase. MDS of the laccase-substrate complexes confirmed their stability during catalytic degradation. Laccase assay results confirmed that the degradation of syringol, dihydroconiferyl alcohol, guaiacol, parathion, isoproturon, and glyphosate were 100%, 99.31%, 95.69%, 60.96%, 54.51%, and 48.34% within 2 h, respectively. Taken together, we describe a novel method to understand the molecular-level biodegradation of xenobiotic compounds through laccase and its potential application in contaminant removal.


Assuntos
Lacase , Paration , Lacase/metabolismo , Lignina/química , Simulação de Acoplamento Molecular , Biodegradação Ambiental , Xenobióticos , Catálise , Simulação de Dinâmica Molecular , Domínio Catalítico
7.
J Nutr Biochem ; 111: 109180, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36240958

RESUMO

Myocardial ischemia leads to cardiac fibrosis along with copper (Cu) loss. Cu repletion diminishes myocardial fibrosis and improves cardiac function. The transformation of fibroblasts to myofibroblasts is highly responsible for the pathogenesis of cardiac fibrosis. This study was undertaken to test the hypothesis that Cu inhibition of cardiac fibrosis results from suppression of myofibroblasts. Rhesus monkeys 4-5 years old were subjected to coronary artery ligation to induce myocardial infarction (MI). At the end of the fourth week after the surgery, an ultrasound-directed Cu-albumin microbubble organ-specific Cu delivery technique was used to treat the ischemia-infarcted monkey hearts twice a week for 4 weeks. This treatment increased Cu concentrations in the infarct area, loosened the collagen cross-linking network, restored blood vessel density, and improved cardiac contractility. Total fibroblasts labeled with vimentin were increased in the infarct area, and Cu repletion did not alter this increase. Myofibroblasts, dually labeled with vimentin and α-smooth muscle actin (α-SMA), were also significantly increased in the infarct area but were significantly reduced by Cu repletion. Correspondingly, the products of myofibroblasts, type I and III collagens and inhibitors of collagenases were significantly reduced. In contrast, metalloproteinase-1 (MMP-1) and MMP-1 producing fibroblasts (vimentin+ and MMP-1+ cells) were significantly increased. These results suggest that Cu inhibits the transformation of fibroblasts to myofibroblasts, leading to a pro-fibrinolytic switch and an improvement in cardiac function.


Assuntos
Infarto do Miocárdio , Miofibroblastos , Humanos , Miofibroblastos/patologia , Vimentina , Cobre , Miocárdio/patologia , Metaloproteinase 1 da Matriz , Fibroblastos , Fibrose
8.
RSC Adv ; 12(47): 30529-30538, 2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36337982

RESUMO

In this paper, a sensitive and specific competitive fluorescence immunoassay (CFIA) method was developed for the qualitative and quantitative analysis of ketamine (KET). A novel competitive model in which ketamine hapten (KET-BSA), coated on microporous plates, competed with ketamine antigen (KET-Ag) in actual samples to bind fluorescein isothiocyanate-labeled antibody (KET-Ab) could be used for rapid and indirect quantitative analysis of KET in human urine, blood, or sewage. In the CFIA method, KET concentration in the sample negatively correlated with the detected fluorescence intensity. The linear correlation coefficient of the competitive quantitative equation was 0.992, the linear range was 0.01-0.5 µg mL-1, and the limit of detection (LOD) was 0.1 pg mL-1. The specificity results showed that the cross-reaction rate of norketamine was less than 10%. Recoveries of spiked samples at low, medium, and high concentrations ranged from 96% to 117%. The CFIA method and classical gas chromatography-tandem mass spectrometry (GC-MS/MS) were used to detect the actual samples simultaneously. The relative deviation of the quantitative results was less than 10%. The LOD value of KET by CFIA was four orders of magnitude lower than that by GC-MS/MS. Additionally, CFIA had great advantages over GC-MS/MS in terms of sample pretreatment and economic investment. In conclusion, this study provided a targeting detection platform for KET, which achieved a rapid, portable, and sensitive analysis of trace KET in various materials.

9.
Front Cardiovasc Med ; 9: 1047577, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36426227

RESUMO

Background: Whether perfusion/metabolism imaging differs between matched ST-segment elevation myocardial infarction (STEMI) patients with and without cardiogenic shock (CS) remains unknown. Methods: Seventeen STEMI patients with CS (13 men, 60 ± 12 years) and 16 matched STEMI patients without CS (15 men, 54 ± 15 years) were prospectively recruited. All patients underwent baseline 99mTc-sestamibi/18F-fluorodeoxyglucose (FDG) imaging and echocardiography 6 ± 2 days post-infarction. Nine patients with CS and seven without CS had repeated imaging 98 ± 7 days post-infarction. The total perfusion deficit (TPD) and total FDG uptake deficit (TFD) were calculated to assess the percentages of impaired perfusion and metabolism over the left ventricle. Patients were followed up for 337 days (213-505 days) and the major adverse cardiac events (MACE) were recorded. Results: TPD was greater in patient with CS and was independently related to the presence of CS (OR: 4.36, p = 0.013). Both acute- and convalescent TFD were inversely related to the improvement ratio of LVEF (r-values: -0.62, -0.73; both p < 0.05). MACE occurred in 16 patients (10 CS and 6 non-CS), and acute TFD was predictive of MACE in those with CS (HR: 2.06, p = 0.038). Conclusion: In this pilot study, we demonstrated that STEMI patients with CS had a significantly increased TPD, which was relevant to the presence of CS. Acute TFD was associated with improvement in LVEF, and was predictive of MACE in patients with CS.

11.
Cancer Gene Ther ; 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36411371

RESUMO

A20 acts as a tumor suppressor in hepatocellular carcinoma, especially inhibiting metastasis of the malignant cells. However, the mechanisms whereby A20 plays the inhibitory roles are not understood completely. Rac1 signaling is essential for cell migration in hepatocellular carcinoma metastasis. Nevertheless, it is not known whether and how A20 inhibits Rac1 signaling to suppress the migration of hepatocellular carcinoma cell. Thereby, we analyzed the relationship between A20 and Rac1 activation, as well as the activity of Akt and mTORC2, two signaling components upstream of Rac1, using gain and loss of function experiments. We found that the overexpression of A20 repressed, while the knockdown or knockout of A20 promoted, the activation of Rac1, Akt and mTORC2 in hepatocellular carcinoma cells. Moreover, the inhibitory effect of A20 on the mTORC2/Akt/Rac1 signaling axis was due to the interaction between A20 and mTORC2 complex. The binding of A20 to mTORC2 was mediated by the ZnF7 domain of A20 and M1 ubiquitin chain in the mTORC2 complex. Furthermore, A20 inhibited metastasis of hepatocellular carcinoma cells via restraining mTORC2 in a hepatocellular carcinoma xenograft mouse model. These findings revealed the relationship between A20 and mTORC2, and explained the molecular mechanisms of A20 in inhibition of hepatocellular carcinoma metastasis.

12.
Int J Ophthalmol ; 15(11): 1752-1756, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36404982

RESUMO

AIM: To evaluate the association of complement factor H (CFH) and microtubule-associated protein 1 light chain 3 beta (MAP1LC3B) gene polymorphisms with the risk of age-related macular degeneration (AMD) in a high-altitude population. METHODS: The study group consisted of 172 participants with symptoms of AMD who were examined and diagnosed between January 2019 and June 2020. The control group was composed of 120 healthy individuals. Each participant was required to provide two milliliters of peripheral blood for DNA extraction. Two single nucleotide polymorphisms (SNPs) of CFH (rs1061170 and rs800292) and two SNPs of MAP1LC3B (rs8044820 and rs9903) were genotyped. The genotypes and allele frequencies of the SNPs in the study and control groups were further compared using Chi-square and Fisher's exact tests. RESULTS: In a high-altitude population, the nominally significant differences of rs800292 and rs9903's genotype AG frequencies were observed in the AMD group (P=0.034 and 0.004, respectively). The frequencies of allele G of rs800292 and allele A of rs9903 were also significantly different in the AMD group compared to the control [(P=0.034, OR=0.70, 95%CI: 0.50-0.98) and (P=0.004, OR=1.60, 95%CI: 1.15-2.22), respectively]. No significant differences in the genotype distributions (P=0.16 and 0.40, respectively) and allele frequencies (P>0.05) of rs1061170 and rs8044820 were observed in the AMD group. CONCLUSION: Genotype AG of rs800292 may be a protective factor for AMD. Conversely, rs9903 seems to be a risk factor for AMD. Therefore, allele G of rs800292 may be a protective factor, and allele A of rs9903, a risk factor for AMD in Qinghai high-altitude population.

13.
Front Plant Sci ; 13: 1035121, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36407599

RESUMO

Cofactors are crucial for the biosynthesis of natural compounds, and cofactor engineering is a useful strategy for enzyme optimization due to its potential to enhance enzyme efficiency. Secoisolariciresinol dehydrogenase (SIRD) was reported to convert secoisolariciresinol into matairesinol in an NAD+-dependent reaction. Here, a SIRD designated as IiSIRD2 identified from Isatis indigotica was found to utilize NADP+ as the cofactor. To explore the structural basis for this unique cofactor preference, model-based structural analysis was carried out, and it was postulated that a variation at the GXGGXG glycine-rich motif of IiSIRD2 alters its cofactor preference. This study paves way for future investigations on SIRD cofactor specificity and cofactor engineering to improve SIRD's catalytic efficiency.

14.
Front Pharmacol ; 13: 986199, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36408259

RESUMO

Objective: T cells represent a predominant cell type in autoimmune disease. However, their exact roles are not fully clear in systemic sclerosis (SSc). This study aimed to mainly investigate the alteration in the absolute numbers of T-lymphocyte subsets and the serum levels of cytokines in SSc patients. Methods: A total of 76 patients with SSc and 76 age- and sex-matched healthy controls (HCs) were enrolled. The levels of circulating T cell subsets and serum cytokines were measured by flow cytometry. T cell subsets or serum cytokines correlations with disease activity and organ involvement were analyzed. Results: The absolute numbers of Th2 and Treg cells in SSc patients were lower than those in HCs (p < 0.05), resulting in the ratios of Th1/Th2 [25.01 (12.24, 38.61) vs. 11.64 (6.38, 20.34)] and Th17/Treg [0.42 (0.17, 0.66) vs. 0.17 (0.13, 0.29)] were increased significantly (p < 0.001). The absolute numbers of total T, Th, and Treg cells were negatively correlated with CRP (r = -0.406, p = 0.002; r = -0.263, p < 0.05; r = -0.367 p < 0.01). The serum levels of IL-2, SIL-2R, IL-6, IL-10, INF-γ, and TNF-α were significantly higher than those in HCs (p < 0.001). Increasing IL-2 in the wake of the augment of ESR (r = 0.671, p = 0.004), so did IL-6 (r = 0.378, p < 0.05). The ratio of Th17/Treg in SSc-ILD patients had lower levels than that in other patients [0.35 (0.14, 0.53) vs. 0.64 (0.26, 0.93) p = 0.028]; Treg cells were lessened in patients with Raynaud's phenomenon relative to controls [3.00 (2.41, 4.28) vs. 3.55 (2.86, 4.53) p < 0.05]. The levels of IL-2, IL-10 and INF-γ [3.32 (1.05,11.73) vs. 2.32 (0.44,6.45), p = 0.045], [8.08 (3.63, 355,77) vs. 4.89 (0.78, 21.44), p = 0.02], [6.31 (2.66, 44.03) vs. 4.03 (0.22, 16.96), p = 0.009] were elevated in patients with arthralgia, while the level of Th17 was decreased [0.62 (0.20,2.16) vs. 1.26 (0.22,10.93), p = 0.026]. ROC curve analysis yielded an optimal cut-off IL-2, IL-10, and INF-γ levels of 2.67, 5.93, and 5.32 pg/ml for the presence of arthralgia. Conclusion: We exhibited abnormalities in T subsets and the production of their cytokines in SSc, as compared with those in HCs. This may allow the pathogenesis of SSc and the development of novel therapeutic interventions aimed at targeting these cells and the cytokines they produce.

15.
Acta Pharmacol Sin ; 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36347997

RESUMO

Previous studies have shown mitochondrial dysfunction in various acute kidney injuries and chronic kidney diseases. Lipoic acid exerts potent effects on oxidant stress and modulation of mitochondrial function in damaged organ. In this study we investigated whether alpha lipoamide (ALM), a derivative of lipoic acid, exerted a renal protective effect in a type 2 diabetes mellitus mouse model. 9-week-old db/db mice were treated with ALM (50 mg·kg-1·d-1, i.g) for 8 weeks. We showed that ALM administration did not affect blood glucose levels in db/db mice, but restored renal function and significantly improved fibrosis of kidneys. We demonstrated that ALM administration significantly ameliorated mitochondrial dysfunction and tubulointerstitial fibrotic lesions, along with increased expression of CDX2 and CFTR and decreased expression of ß-catenin and Snail in kidneys of db/db mice. Similar protective effects were observed in rat renal tubular epithelial cell line NRK-52E cultured in high-glucose medium following treatment with ALM (200 µM). The protective mechanisms of ALM in diabetic kidney disease (DKD) were further explored: Autodock Vina software predicted that ALM could activate RXRα protein by forming stable hydrogen bonds. PROMO Database predicted that RXRα could bind the promoter sequences of CDX2 gene. Knockdown of RXRα expression in NRK-52E cells under normal glucose condition suppressed CDX2 expression and promoted phenotypic changes in renal tubular epithelial cells. However, RXRα overexpression increased CDX2 expression which in turn inhibited high glucose-mediated renal tubular epithelial cell injury. Therefore, we reveal the protective effect of ALM on DKD and its possible potential targets: ALM ameliorates mitochondrial dysfunction and regulates the CDX2/CFTR/ß-catenin signaling axis through upregulation and activation of RXRα. Schematic figure illustrating that ALM alleviates diabetic kidney disease by improving mitochondrial function and upregulation and activation of RXRα, which in turn upregulated CDX2 to exert an inhibitory effect on ß-catenin activation and nuclear translocation. RTEC renal tubular epithelial cell. ROS Reactive oxygen species. RXRα Retinoid X receptor-α. Mfn1 Mitofusin 1. Drp1 dynamic-related protein 1. MDA malondialdehyde. 4-HNE 4-hydroxynonenal. T-SOD Total-superoxide dismutase. CDX2 Caudal-type homeobox transcription factor 2. CFTR Cystic fibrosis transmembrane conductance regulator. EMT epithelial mesenchymal transition. α-SMA Alpha-smooth muscle actin. ECM extracellular matrix. DKD diabetic kidney disease. Schematic figure was drawn by Figdraw ( www.figdraw.com ).

16.
Ying Yong Sheng Tai Xue Bao ; 33(11): 3007-3015, 2022 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-36384835

RESUMO

To explore the differences in structure and diversity of nirK-type denitrifying microbial community in marsh soils at different invasion stages of Spartina alterniflora, the mudflat (MF, before invasion) and the S. alterniflora marsh after seaward invasion for 1-2 years (SAN) and 6-7 years (SA) in Shanyutan of the Minjiang River estuary were investigated by high-through put sequencing method. Results showed that the seaward invasion of S. alterniflora reduced the richness and diversity of nirK-type denitrifying microbial community in marsh soils. The nirK-type denitrifying microbial community in soils at different invasion stages included Proteobacteria and Actinobacteria, with Proteobacteria as the dominant one. The seaward invasion of S. alterniflora greatly altered the composition of nirK-type denitrifying microbial community in marsh soils. The highest relative abundance of genus in soils from different invasion stages were Bradyrhizobium, Mesorhizobium and Alcaligenes, respectively. The seaward invasion of S. alterniflora increased the spatial heterogeneity of nirK-type denitrifying microbial community composition in marsh soils. In SAN plot, the enhancement of spatial heterogeneity was primarily due to higher environmental disturbances in plots and the increased spatial heterogeneity of environmental variables caused by the seaward invasion of S. alterniflora. The seaward invasion of S. alterniflora altered the physico-chemical properties (e.g., grain composition, pH and moisture) and N nutrient conditions (total N, NH4+-N and NO3--N) in marsh soils, which greatly altered the structure and diversity of nirK-type denitrifying microbial community. Our findings reveal the microbial mechanism of denitrification process in marsh soils during the seaward invasion of S. alterniflora.


Assuntos
Microbiota , Áreas Alagadas , Solo/química , Estuários , Rios , Espécies Introduzidas , Poaceae
17.
ACS Appl Mater Interfaces ; 14(45): 50890-50899, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36343091

RESUMO

A lithium metal anode (LMA) is appealing due to its high theoretical capacity and low electrochemical potential. Unfortunately, the practical application of LMAs is restricted by the uncontrollable Li dendrite growth and tremendous volume change. Herein, lithiophilic honeycomb-like layered double hydroxide (LDH) nanosheet arrays supported on a flexible carbon cloth (NiMn-LDHs NAs@CC) are synthesized as the Li host to spatially confine the Li deposition, guiding Li growth via a conformal and uniform manner. First, the lithiophilic NiMn-LDHs NAs as nucleation seeds render the CC substance outstanding lithiophilicity and reduce the nucleation barrier. The hierarchical honeycomb-like structure then directs the oriented Li deposition and provides an open channel for fast ion transport. Finally, the CC skeleton offers a high specific surface for decreasing the inhomogeneous distribution of the current density and enough space for alleviating the volume variations, synergistically inhibiting the dendritic Li growth. As a consequence, the NiMn-LDHs NAs@CC symmetric cell exhibits a low overpotential of less than 17 mV at 2 mA cm-2 and a long lifespan of 2100 h at 3 mA cm-2. In addition, when paired with the LiNiCoMnO2 (NCM111) cathode, the NiMn-LDHs NAs@CC@Li full cell presents enhanced cycling stability and rate capability in comparison to the CC@Li full cell, implying the great potential of the NiMn-LDHs NAs@CC in stabilizing the LMA.

18.
Front Oncol ; 12: 971871, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36387085

RESUMO

Objectives: To propose a deep learning-based classification framework, which can carry out patient-level benign and malignant tumors classification according to the patient's multi-plane images and clinical information. Methods: A total of 430 cases of spinal tumor, including axial and sagittal plane images by MRI, of which 297 cases for training (14072 images), and 133 cases for testing (6161 images) were included. Based on the bipartite graph and attention learning, this study proposed a multi-plane attention learning framework, BgNet, for benign and malignant tumor diagnosis. In a bipartite graph structure, the tumor area in each plane is used as the vertex of the graph, and the matching between different planes is used as the edge of the graph. The tumor areas from different plane images are spliced at the input layer. And based on the convolutional neural network ResNet and visual attention learning model Swin-Transformer, this study proposed a feature fusion model named ResNetST for combining both global and local information to extract the correlation features of multiple planes. The proposed BgNet consists of five modules including a multi-plane fusion module based on the bipartite graph, input layer fusion module, feature layer fusion module, decision layer fusion module, and output module. These modules are respectively used for multi-level fusion of patient multi-plane image data to realize the comprehensive diagnosis of benign and malignant tumors at the patient level. Results: The accuracy (ACC: 79.7%) of the proposed BgNet with multi-plane was higher than that with a single plane, and higher than or equal to the four doctors' ACC (D1: 70.7%, p=0.219; D2: 54.1%, p<0.005; D3: 79.7%, p=0.006; D4: 72.9%, p=0.178). Moreover, the diagnostic accuracy and speed of doctors can be further improved with the aid of BgNet, the ACC of D1, D2, D3, and D4 improved by 4.5%, 21.8%, 0.8%, and 3.8%, respectively. Conclusions: The proposed deep learning framework BgNet can classify benign and malignant tumors effectively, and can help doctors improve their diagnostic efficiency and accuracy. The code is available at https://github.com/research-med/BgNet.

19.
Artigo em Inglês | MEDLINE | ID: mdl-36321167

RESUMO

Contemporary systems for the diagnosis and management gastrointestinal symptoms not attributable to organic diseases (Functional GI Disorders, FGID, now renamed Disorders of Gut-Brain Interaction, DGBI) seek to categorize patients into narrowly defined symptom-based sub-classes to enable targeted treatment of patient cohorts with similar underlying putative pathophysiology. However, an overlap of symptom categories frequently occurs and has a negative impact on treatment outcomes. There is a lack of guidance on their management. An Asian Pacific Association of Gastroenterology (APAGE) working group was set up to develop clinical practice guidelines for management of patients with functional dyspepsia (FD) who have an overlap with another functional gastrointestinal disorder: FD with gastroesophageal reflux (FD-GERD), epigastric pain syndrome with irritable bowel syndrome (EPS-IBS), postprandial distress syndrome with IBS (PDS-IBS), and FD-Constipation. We identified putative pathophysiology to provide a basis for treatment recommendations. A management algorithm is presented to guide primary and secondary care clinicians.

20.
BMC Complement Med Ther ; 22(1): 310, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36434600

RESUMO

BACKGROUND: Anoxia is characterized by changes in the morphology, metabolism, and function of tissues and organs due to insufficient oxygen supply or oxygen dysfunction. Gentiana straminea Maxim (G.s Maxim) is a traditional Tibetan medicine. Our previous work found that G.s Maxim mediates resistance to hypoxia, and we found that the ethyl acetate extract had the best effect. Nevertheless, the primary anti-hypoxia components and mechanisms of action remain unclear. METHODS: Compounds from the ethyl acetate extraction of G.s Maxim were identified using UPLC-Triple TOF MS/MS. Then Traditional Chinese Medicine Systematic Pharmacology Database was used to filtrate them. Network pharmacology was used to forecast the mechanisms of these compounds. Male specific pathogen-free Sprague Dawley rats were randomly divided into six groups: (1) Control; (2) Model; (3) 228 mg/kg body weight Rhodiola capsules; (4) 6.66 g/kg body weight the G.s Maxim's ethyl acetate extraction; (5) 3.33 g/kg body weight the G.s Maxim's ethyl acetate extraction; (6) 1.67 g/kg body weight the G.s Maxim's ethyl acetate extraction. After administering intragastric ally for 15 consecutive days, an anoxia model was established using a hypobaric oxygen chamber (7000 m, 24 h). Then Histology, enzyme-linked immunosorbent assays, and western blots were performed to determine these compounds' anti-hypoxic effects and mechanisms. Finally, we performed a molecular docking test to test these compounds using Auto Dock. RESULTS: Eight drug-like compounds in G.s Maxim were confirmed using UPLC-Triple TOF MS/MS and Lipinski's rule. The tumor necrosis factor (TNF) signaling pathway, the hypoxia-inducible factor 1 (HIF-1) signaling pathway, and the nuclear factor kappa-B (NF-κB) signaling pathway was signaling pathways that G.s Maxim mediated anti-anoxia effects. The critical targets were TNF, Jun proto-oncogene (JUN), tumor protein p53 (TP53), and threonine kinase 1 (AKT1). Animal experiments showed that the ethyl acetate extraction of G.s Maxim ameliorated the hypoxia-induced damage of hippocampal nerve cells in the CA1 region and reversed elevated serum expression of TNF-α, IL-6, and NF-κ B in hypoxic rats. The compound also reduced the expression of HIF-1α and p65 and increased the Bcl-2/Bax ratio in brain tissue. These findings suggest that G.s Maxim significantly protects against brain tissue damage in hypoxic rats by suppressing hypoxia-induced apoptosis and inflammation. Ccorosolic acid, oleanolic acid, and ursolic acid had a strong affinity with core targets. CONCLUSIONS: The ethyl acetate extraction of G.s Maxim mediates anti-hypoxic effects, possibly related to inhibiting apoptosis and inflammatory responses through the HIF-1/NF-κB pathway. The primary active components might be corosolic, oleanolic, and ursolic acids.


Assuntos
Gentiana , Masculino , Animais , Ratos , Gentiana/metabolismo , Espectrometria de Massas em Tandem , NF-kappa B/metabolismo , Simulação de Acoplamento Molecular , Farmacologia em Rede , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo , Oxigênio , Peso Corporal
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