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1.
J Appl Microbiol ; 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35490292

RESUMO

AIMS: The emerging of drug resistant Pseudomonas aeruginosa is a critical challenge and renders an urgent action to discover innovative antimicrobial interventions. One of these interventions is to disrupt the pseudomonas quinolone signal (pqs) quorum sensing (QS) system, which governs multiple virulence traits and biofilm formation. This study aimed to investigate the QS inhibitory activity of a series of new PqsR inhibitors bearing a quinoline scaffold against Ps. aeruginosa. METHODS AND RESULTS: The results showed that compound 1 suppressed the expression of QS-related genes and showed the best inhibitory activity to the pqs system of wild-type Ps. aeruginosa PAO1 with an IC50 of 20.22 µmol L-1 . The virulence factors including pyocyanin, total protease, elastase and rhamnolipid were significantly suppressed in a concentration-dependent manner with the compound. In addition, compound 1 in combination with tetracycline inhibited synergistically the bacterial growth and suppressed the biofilm formation of PAO1. The molecular docking studies also suggested that compound 1 could potentially interact with the ligand-binding domain of the Lys-R type transcriptional regulator PqsR as a competitive antagonist. CONCLUSIONS: The quinoline-based derivatives were found to interrupt the quorum sensing system via the pqs pathway and thus the production of virulence factors was inhibited and the antimicrobial susceptibility of Ps. aeruginosa was enhanced. SIGNIFICANCE AND IMPACT OF STUDY: The study showed that the quinoline-based derivatives could be used as an anti-virulence agent for treating Ps. aeruginosa infections.

2.
Clin Transl Med ; 12(5): e821, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35522918

RESUMO

BACKGROUND: During pregnancy, mother-child interactions trigger a variety of subtle changes in the maternal body, which may be reflected in the status of peripheral blood mononuclear cells (PBMCs). Although these cells are easy to access and monitor, a PBMC atlas for pregnant women has not yet been constructed. METHODS: We applied single-cell RNA sequencing (scRNA-seq) to profile 198,356 PBMCs derived from 136 pregnant women (gestation weeks 6 to 40) and a control cohort. We also used scRNA-seq data to establish a transcriptomic clock and thereby predicted the gestational age of normal pregnancy. RESULTS: We identified reconfiguration of the peripheral immune cell phenotype during pregnancy, including interferon-stimulated gene upregulation, activation of RNA splicing-related pathways and immune activity of cell subpopulations. We also developed a cell-type-specific model to predict gestational age of normal pregnancy. CONCLUSIONS: We constructed a single-cell atlas of PBMCs in pregnant women spanning the entire gestation period, which should help improve our understanding of PBMC composition turnover in pregnant women.


Assuntos
Leucócitos Mononucleares , Gestantes , Feminino , Idade Gestacional , Humanos , Imunofenotipagem , Leucócitos Mononucleares/metabolismo , Gravidez , Transcriptoma
3.
Adv Sci (Weinh) ; : e2200023, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35508900

RESUMO

Sodium-ion batteries (SIBs) are regarded as a kind of promising candidate for large-scale energy storage technology. The development of advanced carbon anodes with high Na-storage capacity and initial Coulombic efficiency (ICE) from low cost, resources abundant precursors is critical for SIBs. Here, a carbon microcrystalline hybridization route to synthesize hard carbons with extensive pseudo-graphitic regions from lignite coal with the assistance of sucrose is proposed. Employing the cross-linked interaction between sucrose and lignite coal to generate carbon-based hybrid microcrystalline states, the obtained hard carbons possess pseudo-graphitic dominant phases with large interlayer spaces that facilitate Na ion's storage and transportation, as well as fewer surface defects that guarantee high ICE. The LCS-73 with an optimum cross-link demonstrates the highest Na-storage capacity of 356 mAh g-1 and an ICE of 82.9%. The corresponding full-cell delivers a high energy density of 240 Wh kg-1 (based on the mass of anode and cathode materials) and excellent rate capability of 106 mAh g-1 at 10 C in addition to outstanding cycle performance with 80% retention over 500 cycles at 2 C. The proposed work offers an efficient route to develop high-performance, low-cost carbon-based anode materials with potential application for advanced SIBs.

4.
Sci Data ; 9(1): 154, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35383200

RESUMO

Despite the close linkage between extreme floods and snowmelt, particularly through rain-on-snow (ROS), hydrologic infrastructure is mostly designed based on standard precipitation Intensity-Duration-Frequency curves (PREC-IDF) that neglect snow processes in runoff generation. For snow-dominated regions, such simplification could result in substantial errors in estimating extreme events and infrastructure design risk. To address this long-standing problem, we applied the Next Generation IDF (NG-IDF) technique to estimate design basis extreme events for different durations and return periods in the conterminous United States (CONUS) to distinctly represent the contribution of rain, snowmelt, and ROS events to the amount of water reaching the land surface. A suite of datasets were developed to characterize the magnitude, trend, seasonality, and dominant mechanism of extreme events for over 200,000 locations. Infrastructure design risk associated with the use of PREC-IDF was estimated. Accuracy of the model simulations used in the analyses was confirmed by long-term snow data at over 200 Snowpack Telemetry stations. The presented spatially continuous datasets are readily usable and instrumental for supporting site-specific infrastructure design.

5.
J Nat Prod ; 85(4): 987-996, 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35380848

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive neoplastic diseases of the pancreas with fatal proliferation and metastasis and no medicine available for treatment. From an Antarctica sponge-derived fungus, Aspergillus insulicola HDN151418, four new nitrobenzoyl sesquiterpenoids, namely, insulicolides D-G (1-4), were isolated. Compounds 3 and 4 exhibited selective inhibition against human PDAC cell lines. Further studies indicated that compound 4 could significantly suppress cell proliferation to induce apoptosis and blocked migration and invasion of PDAC cells. Compound 4 could also avoid resistance and improved the therapeutic effect of the chemotherapy drug gemcitabine. A preliminary mechanism study showed that compound 4 can significantly inhibit the expression of EGFR and XIAP in PDAC cells. Altogether, 4 is a potential lead compound for anti-PDAC drug research.


Assuntos
Antineoplásicos , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Sesquiterpenos , Regiões Antárticas , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Aspergillus , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Sesquiterpenos/farmacologia , Sesquiterpenos/uso terapêutico
6.
Cell Rep ; 39(2): 110635, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35417690

RESUMO

Circadian genes such as Clock, Bmal1, Cryptochrome1/2, and Period1/2/3 constitute the precise circadian system. ClockΔ19 is a commonly used mouse model harboring a circadian clock gene mutation, which lacks the EXON-19-encoded 51 amino acids. Previous reports have shown that ClockΔ19 mice have severe metabolic abnormalities. Here, we report that the mitochondria of ClockΔ19 mice exhibit excessive fission and dysfunction. We also demonstrate that CLOCK binds to the RNA-binding protein PUF60 through its EXON 19. Further, we find that PUF60 directly maintains mitochondrial homeostasis through regulating Drp1 mRNA stability, while the association with CLOCK can competitively inhibit this function. In ClockΔ19 mice, CLOCKΔ19 releases PUF60, leading to enhanced Drp1 mRNA stability and persistent mitochondrial fission. Our results reveal a direct post-transcriptional role of CLOCK in regulating mitochondrial homeostasis via Drp1 mRNA stability and that the loss of EXON 19 of CLOCK in ClockΔ19 mice leads to severe mitochondrial homeostasis disorders.


Assuntos
Proteínas CLOCK , Relógios Circadianos , Animais , Proteínas CLOCK/genética , Proteínas CLOCK/metabolismo , Relógios Circadianos/genética , Homeostase/genética , Camundongos , Mitocôndrias/metabolismo , Dinâmica Mitocondrial , Estabilidade de RNA
7.
Eur J Med Chem ; 236: 114360, 2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35421657

RESUMO

The discovery of small molecular inhibitors targeting essential and conserved bacterial drug targets such as FtsZ protein is a promising approach to fight against multi-drug resistant bacteria. In the present study, two new series of FtsZ inhibitors based on a 1-methylquinolinium scaffold were synthesized. The inhibitors possess a variety of substituent groups including the cyclic or linear amine skeleton at the 2- and 4-position of the quinolinium ring for structure-activity relationship study. In general, the inhibitors bearing a cyclic amine substituent at the 4-position of the quinolinium ring showed better antibacterial activity (MIC down to 0.25 µg/mL) than that at the 2-position, especially against Gram-positive bacteria. Among the twenty FtsZ inhibitors examined in various assays, A3 was identified to exhibit excellent antibacterial activity against S. aureus (MIC = 0.5-1 µg/mL), S. epidermidis (MIC = 0.25 µg/mL) and E. faecium (MIC = 1-8 µg/mL). More importantly, A3 showed low hemolytic toxicity (IC5 = 64 µg/mL) and was found not readily to induce drug resistance. A3 at 2-8 µg/mL promoted the polymerization of FtsZ and interrupted the bacterial division. Furthermore, the ligand-FtsZ interaction study conducted with circular dichroism and molecular docking revealed that A3 induced secondary structure changes of FtsZ protein upon binding to the interdomain cleft of the protein. A3 is thus a potent inhibitor of FtsZ and shows potential to be used as a new antibacterial agent against drug-resistant bacteria.

8.
Gene Ther ; 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35383288

RESUMO

Therapies for genetic disorders caused by mutated mitochondrial DNA are an unmet need, in large part due barriers in delivering DNA to the organelle and the absence of relevant animal models. We injected into mouse eyes a mitochondrially targeted Adeno-Associated-Virus (MTS-AAV) to deliver the mutant human NADH ubiquinone oxidoreductase subunit I (hND1/m.3460 G > A) responsible for Leber's hereditary optic neuropathy, the most common primary mitochondrial genetic disease. We show that the expression of the mutant hND1 delivered to retinal ganglion cells (RGC) layer colocalizes with the mitochondrial marker PORIN and the assembly of the expressed hND1 protein into host respiration complex I. The hND1-injected eyes exhibit hallmarks of the human disease with progressive loss of RGC function and number, as well as optic nerve degeneration. We also show that gene therapy in the hND1 eyes by means of an injection of a second MTS-AAV vector carrying wild-type human ND1 restores mitochondrial respiratory complex I activity, the rate of ATP synthesis and protects RGCs and their axons from dysfunction and degeneration. These results prove that MTS-AAV is a highly efficient gene delivery approach with the ability to create mito-animal models and has the therapeutic potential to treat mitochondrial genetic diseases.

9.
Front Neurosci ; 16: 849158, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35418833

RESUMO

Background: Major depressive disorder (MDD) with suicide attempts (SA) poses a significant public health issue. This study aims to identify neurobiological markers for MDD with SA on resting-state brain functional magnetic resonance imaging (rs-fMRI). Methods: Fifty-one unmedicated adult MDD participants, 27 with SA on the Beck Scale for Suicidal Ideation and 24 without SA, underwent rs-fMRI scanning. A group of 30 healthy controls (HC) matched for age, gender, and education-level with MDD were chosen. A whole brain analysis of regional homogeneity (ReHo) was performed on subjects to identify regions where brain activity was associated with SA. Multiple comparison analysis was performed for ReHo. Pearson's correlation analysis was performed between HAMD-SA scores and ReHo. The statistical significance level was set at p < 0.05. Results: We examined whether there were significant differences among the three groups in whole brain ReHo during resting state. Subjects with SA showed significant increase of ReHo in the right Cingulum Post in comparison with those without SA. Subjects with SA showed significant decrease of ReHo in the right Cingulate Gyrus/Precuneus in comparison with HC. The mean ReHo from the significant brain region was associated with HAMD-SA (item 3 of the HAMD) scores (r = 0.349, P = 0.012) but was not associated with HAMD-24 scores. Conclusion: These results indicate that SA is associated with altered resting-state brain activity. The pattern of elevated activity in the cingulum functioning may be related to SA. Identifying cingulum activity associated with SA may help to elucidate its pathogenesis and etiology.

10.
Front Genet ; 13: 865015, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35386281

RESUMO

Objectives: Mood disorders are a kind of serious mental illness, although their molecular factors involved in the pathophysiology remain unknown. One approach to examine the molecular basis of mood disorders is co-expression network analysis (WGCNA), which is expected to further divide the set of differentially expressed genes into subgroups (i.e., modules) in a more (biologically) meaningful way, fascinating the downstream enrichment analysis. The aim of our study was to identify hub genes in modules in mood disorders by using WGCNA. Methods: Microarray data for expression values of 4,311,721 mRNA in peripheral blood mononuclear cells drawn from 21 MDD, 8 BD, and 24 HC individuals were obtained from GEO (GSE39653); data for genes with expression in the bottom third for 80% or more of the samples were removed. Then, the top 70% most variable genes/probs were selected for WGCNA: 27,884 probes representing 21,840 genes; correlation between module genes and mood disorder (MDD+BD vs. HC) was evaluated. Results: About 52% of 27,765 genes were found to form 50 co-expression modules with sizes 42-3070. Among the 50 modules, the eigengenes of two modules were significantly correlated with mood disorder (p < 0.05). The saddlebrown module was found in one of the meta-modules in the network of the 50 eigengenes along with mood disorder, 6 (IER5, NFKBIZ, CITED2, TNF, SERTAD1, ADM) out of 12 differentially expressed genes identified in Savitz et al. were found in the saddlebrown module. Conclusions: We found a significant overlap for 6 hub genes (ADM, CITED2, IER5, NFKBIZ, SERTAD1, TNF) with similar co-expression and dysregulation patterns associated with mood disorder. Overall, our findings support other reports on molecular-level immune dysfunction in mood disorder and provide novel insights into the pathophysiology of mood disorder.

11.
BMC Public Health ; 22(1): 688, 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35395755

RESUMO

BACKGROUND: Exposure to famine during early life is related to several adverse health outcomes in adulthood, but the effect of famine exposure during adolescence is unclear. This study aims to examine whether exposure to famine in adolescence is associated with metabolic syndrome (MetS) in adulthood. METHODS: This study included 4130 Chinese adults (2059 males and 2071 females) aged 59-71 from the 2011 China Health and Retirement Longitudinal Study (CHARLS). All the selected participants were exposed to the three-year time period (1959-1961) of China's Great Famine. Participants were categorized into an adolescent-exposed group (born 01/01/1944-12/31/1948) and a non-adolescent-exposed group (born 01/01/1940-12/31/1941 and 01/01/1951-12/31/1952). Sex-stratified multiple logistic regression models were used to estimate the association between exposure to famine in adolescence and MetS. RESULTS: Participants exposed to famine during adolescence were more likely to report MetS (aOR = 1.35; 95%CI 1.01-1.78) compared to the non-adolescent-exposed group. Further, males were 45% less likely to report MetS than females (aOR = 0.55; 95%CI 0.36-0.83). After stratification by sex, the effects of famine exposure during adolescence on MetS were detected among males only (aOR = 1.97; 95%CI 1.20-3.24). Additionally, males with a history of drinking were more likely to report MetS compared to those with no history of drinking (aOR = 2.63; 95%CI 1.41-4.90). CONCLUSIONS: Our findings reveal that exposure to famine during adolescence is associated with higher odds of MetS in adulthood overall, and this association is only pronounced among males. This study emphasizes that undernutrition in early life, including adolescence, may have a long-term effect and be associated with adverse health events in middle-to-late life. Targeting those elderly people who suffered famine during adolescence may help prevent the development of MetS in later life.


Assuntos
Síndrome Metabólica , Efeitos Tardios da Exposição Pré-Natal , Inanição , Adolescente , Adulto , Idoso , China/epidemiologia , Fome Epidêmica , Feminino , Humanos , Estudos Longitudinais , Masculino , Síndrome Metabólica/epidemiologia , Estudos Retrospectivos , Inanição/epidemiologia
12.
Cell Regen ; 11(1): 9, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35362769

RESUMO

Myocardial regeneration has been considered a promising option for the treatment of adult myocardial injuries. Previously, a chick early amniotic fluid (ceAF) preparation was shown to contain growth-related factors that promoted embryonic growth and cellular proliferation, though the nature of the components within ceAF were not fully defined. Here we tested whether this ceAF preparation is similarly effective in the promotion of myocardial regeneration, which could provide an alternative therapeutic for intervening myocardial injury. In this study, a myocardial ischemic injury model was established in adult mice and pigs by multiple research entities, and we were able to show that ceAF can efficiently rescue damaged cardiac tissues and markedly improve cardiac function in both experimental models through intravenous administration. ceAF administration increased cell proliferation and improved angiogenesis, likely via down-regulation of Hippo-YAP signaling. Our data suggest that ceAF administration can effectively rescue ischemic heart injury, providing the key functional information for the further development of ceAF for use in attenuating myocardial injury.

13.
Artigo em Inglês | MEDLINE | ID: mdl-35445772

RESUMO

AIM: Gut microbiota and its metabolite bile acids may play a significant role in the occurrence and development of major depressive disorder (MDD). Therefore, this study analyzes gut microbiota and bile acids, as well as their correlation in patients. METHODS: 31 MDD patients and 29 healthy controls (HCs) were enrolled in this study. We collected their both blood and feces. Plasma bile acid content was determined by liquid chromatography-mass spectrometry (LC-MS); gut microbiota was detected by 16SrRNA gene sequencing and subsequently analyzed. We also analyzed the correlation between different gut microbiota, bile acids, and HAMD score. RESULTS: The α-diversity analysis found that Simpson and Pielou's evenness index were much higher in HCs than those in the MDD patients. The ß-diversity of the two groups were differences by NMDS analysis. LEfSe analysis identified 16 different strains. Bile acids detection showed that NorDCA in MDD patients was significantly higher than in HCs, whereas TLCA, GLCA, and LCA-3S were significantly lower. Spearman correlation analysis showed that Turicibacteraceae, Turicibacterales, and Turicibacter were positively related with TLCA, GLCA, GDCA, and TDCA, and were negatively correlated with HAMD score. At the same time, TLCA , GLCA, and GDCA were negatively correlated with HAMD score. CONCLUSIONS: Gut microbiota and bile acids metabolism are disturbances in MDD, and there exists a correlation between gut microbiota and bile acids metabolism. Moreover, their interaction may be related to the pathophysiological mechanism of MDD. This article is protected by copyright. All rights reserved.

14.
Front Microbiol ; 13: 847468, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35432260

RESUMO

The negative effects of ethanol (EtOH) abuse on the body have been widely reported in recent years. Building on the microbiota-gut-brain axis hypothesis, our study aimed to demonstrate the potential psychobiotic role of Lactobacillus johnsonii BS15 in the preventive effects of acute EtOH intake on memory impairment. We also determined whether L. johnsonii BS15 intake could effectively improve resistance to acute drinking and alleviate the adverse effects of EtOH. Male mice were fed L. johnsonii BS15 orally with (Probiotic group) or without (Control and Alcohol groups) daily dose of 0.2 × 109 CFU/ml per mouse for 28 days. Gavage with L. johnsonii BS15 significantly modified the ileal microbial ecosystem (assessed by 16S rRNA gene sequencing) in favor of Firmicutes and Lactobacillus, indicating the ability of BS15 to restore the gut microbiota. The acute EtOH exposure model (7 g/kg EtOH per mice) was established by gavage, which was administered to the alcohol and probiotic groups on day 28 of the experiment. The L. johnsonii BS15 intake effectively reduced alcohol unconsciousness time, blood alcohol concentration, and serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Meanwhile, the improvement of ethanol resistance time and the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in the liver were shown by BS15 in acute alcohol-induced mice. We found that acute EtOH exposure reduced the exploration ratio (assessed by the novel object recognition test), escape latency, number of errors (assessed by passive avoidance test), and spontaneous exploration (assessed by T-maze test) in mice, which were obviously improved by L. johnsonii BS15. In the hippocampus, L. johnsonii BS15 significantly reversed the decrease in antioxidant capacity of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) and mRNA expression of memory-related functional proteins of brain-derived neurotrophic factor (BDNF) and cyclic ampresponse element binding protein (CREB) in the hippocampal tissue after acute EtOH exposure. In conclusion, L. johnsonii BS15 intake appears as a promising psychoactive therapy to ameliorate alcohol-mediated memory impairment by increasing EtOH metabolic levels.

15.
Front Pharmacol ; 13: 852550, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35359850

RESUMO

The Fuyou (Fy) formula is an in-hospital preparation consisting of traditional Chinese medicine (TCM) that has been used for treating precocious puberty (PP) for more than 20 years. In this study, we aimed to clarify the effect of the Fy formula and its major components on PP. To confirm the effect of the Fy formula on the release of hypothalamic gonadotropin-releasing hormone (GnRH), GT1-7 cells were treated with estrogen to build the model group and subsequently treated with the Fy formula and its major components to explore their effects on the secretion of GnRH. The level of GnRH in GT1-7 cells was determined using enzyme-linked immunosorbent assay. The results illustrated that, compared to the model group, the Fy formula inhibited the release of GnRH. In addition, the expression levels of proteins related to GnRH secretion, including GnRH, gonadotropin-releasing hormone receptor (GnRHR), Kiss-1 metastasis-suppressor (Kiss1), G-protein coupled receptor 54 (GPR54), estrogen receptor α (ERα), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor-1 receptor (IGF-1R), were detected by real-time polymerase chain reaction (RT-qPCR). The results demonstrated that the Fy formula significantly reduced the level of GnRH secretion in the GT1-7 cell lines compared with the model group. Moreover, it significantly downregulated the expression of GnRH, GnRHR, Kiss1, GPR54, ERα, IGF-1, and IGF-1R. In summary, our results indicate that the Fy formula and its major components may inhibit the effects of estrogen, which alleviates PP through transcriptional regulation of target genes.

16.
Front Immunol ; 13: 855426, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35371037

RESUMO

Background: Chicken meat is one of the most consumed meats worldwide and poultry production is increasing at an exponential rate. Reducing antibiotic usage has resulted in the recurrence of subclinical necrotic enteritis again and influenced global poultry production. Probiotics are potential antibiotic substitutes that can be used to prevent subclinical necrotic enteriti. However, the precise mechanism of action of probiotics and information on which gut microbes confer this efficacy remain elusive. Methods and results: The subclinical necrotic enteritis animal model was used to reveal the mechanism underlying the effect of probiotics on intestinal health through RNA sequencing and 16S rDNA amplicon sequencing. Bacillus licheniformis H2 feeding significantly reduced the relative abundance of Clostridium perfringens in the ileum and markedly ameliorated the pathological damage in the ileum and liver. In addition, oral administration of B. licheniformis H2 contributed to the enhancement of the intestinal barrier function and epithelial renewal, reducing energy consumption, and improving enteral nutrition absorption. Probiotic B. licheniformis H2 also ameliorated the inflammatory response and increased the immunity of subclinical necrotic enteritis infected broilers. Finally, B. licheniformis H2 feeding regulated liver gene expression to suppress immune response and promoted growth and metabolism depending on the gut microbiota. Conclusions: These results indicated the mechanism of probiotic action of B. licheniformis H2 in maintaining intestinal health and thus promoting growth and B. licheniformis H2 may serve as an antibiotic substitute to prevent subclinical necrotic enteritis in poultry farming.


Assuntos
Infecções por Clostridium , Enterite , Enterocolite Necrosante , Microbiota , Doenças das Aves Domésticas , Probióticos , Animais , Antibacterianos , Galinhas , Infecções por Clostridium/prevenção & controle , Infecções por Clostridium/veterinária , Enterite/prevenção & controle , Enterite/veterinária , Doenças das Aves Domésticas/prevenção & controle
17.
J Agric Food Chem ; 70(14): 4353-4361, 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35380825

RESUMO

Chronic stress causes duodenal damage, in which iron death is likely to play an important role. Chlorogenic acid (CGA), one of the most widely consumed dietary polyphenols, has been shown to protect the intestine. However, it is unclear whether CGA exerts a duodenoprotective effect in chronic stress by inhibiting ferroptosis. In this work, rats were daily exposed to restraint stress for 6 h over 21 consecutive days, with/without CGA (100 mg/kg, gavage). CGA reduced blood hepcidin, iron, reactive oxygen species (ROS), and ferroportin 1 (FPN1) levels and upregulated the levels of ferroptosis-related biomarkers (GPX4, GSH, NADPH, etc.). These results confirmed that CGA inhibited ferroptosis in the duodenum. Furthermore, the use of S3I-201 (STAT3 inhibitor) helped to further clarify the mechanism of action of CGA. Overall, CGA could reduce hepcidin production by inhibiting the IL-6/JAK2/STAT3 pathway in the liver to increase the expression of FPN1 in the duodenum, which restored iron homeostasis and inhibited ferroptosis, alleviating chronic stress-induced duodenal injury.


Assuntos
Ferroptose , Animais , Ácido Clorogênico , Duodeno/metabolismo , Ferroptose/genética , Hepcidinas/genética , Interleucina-6/genética , Interleucina-6/farmacologia , Ferro/metabolismo , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Ratos , Transdução de Sinais
19.
Front Neurosci ; 16: 831278, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35250466

RESUMO

OBJECTIVE: For major depressive disorder (MDD), there has been a lack of neuroimaging markers of efficacy of pharmacological treatment. In this study, we aimed to explore the neuroimaging mechanisms in patients with first-episode MDD and identify markers that predict the efficacy of 5-hydroxytryptamine reuptake inhibitors (SSRIs) with the use of resting-state brain imaging technology. METHODS: A total of 101 patients with first-episode MDD and 53 normal controls were finally included in this study. Based on the reduction rate of the score of Hamilton Depression Rating Scale (HAMD-17) during the 2-week SSRI treatment, 31 patients were assigned into the unresponsive group and 32 were assigned into the responsive group. The brain function was compared between patients with MDD and normal controls, and the diagnostic value of brain function was analyzed. With brain regions showing differences between patients with MDD and normal controls as a mask, and the brain function between the responsive and unresponsive groups were compared. Correlations between brain function the HAMD-17 score reduction rate during the 2-week SSRI treatment were analyzed. RESULTS: Compared to normal controls, patients with MDD showed increased ReHo in the left parahippocampal gyrus and right parahippocampal gyrus, decreased ReHo in the right middle occipital gyrus, and decreased functional connectivity between the right and left parahippocampal gyri, right middle occipital gyrus and middle temporal gyrus. Receiver operator characteristic (ROC) curve analysis showed that the area under the curve (AUC) was 0.544 (95% CI: 0.445-0.644) for ReHo and 0.822 (95% CI: 0.734-0.909) for functional connectivity. Logistic regression pooling of the differences in ReHo mean time series with the functional connectivity mean time series was performed for the ROC curve analysis, which showed an AUC of 0.832 (95% CI: 0.752-0.911). Compared to the responsive group, the unresponsive group showed elevated ReHo in the right parahippocampal gyrus and lower functional connectivity in the middle temporal gyrus. We also found that the ReHo value was negatively correlated with the HAMD-17 score reduction after 2 weeks of SSRI treatment. CONCLUSION: Altered resting-state brain function in some regions might be a neurobiological marker for the diagnosis of MDD, and ReHo values are expected to be predictors of patient response to treatment with SSRIs. CLINICAL TRIAL REGISTRATION: [http://www.chictr.org.cn/], identifier [ChiCTR1900028722].

20.
Pediatr Surg Int ; 38(6): 927-934, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35325284

RESUMO

PURPOSE: Malignant tumours of the vagina are very rare in children. The purpose of this study was to retrospectively analyse the clinical presentation, treatment, and outcome of vaginal tumours in children treated in a single institution. METHODS: This study retrospectively analysed the clinical data of children diagnosed with vaginal malignant tumours who were admitted to the Beijing Children's Hospital of Capital Medical University from January 2007 to December 2020 and followed these patients to observe their prognoses and outcomes. RESULTS: During 13 years, a total of 33 children were included in this study, including 13 children with rhabdomyosarcoma and 20 children with endodermal sinus tumours. The average age at diagnosis was 20.4 months. The main clinical manifestations were vaginal bleeding and protruding masses. Of the 13 children with vaginal rhabdomyosarcoma, 12 were treated with multidrug chemotherapy combined with conservative tumour resection, and their tumours completely resolved; only one child underwent vaginectomy and hysterectomy. Twenty children with vaginal endodermal sinus received PEB chemotherapy. Among these patients, the tumour disappeared after chemotherapy in 12 children, and the remaining nodular tumour foci in 8 children were confirmed to be necrotic tissue by pathology. CONCLUSION: Our research confirms that chemotherapy combined with conservative surgical treatment is effective for treating children with vaginal malignancies.


Assuntos
Tumor do Seio Endodérmico , Rabdomiossarcoma , Neoplasias Vaginais , Criança , Tumor do Seio Endodérmico/patologia , Feminino , Hospitais , Humanos , Lactente , Estudos Retrospectivos , Rabdomiossarcoma/diagnóstico , Rabdomiossarcoma/epidemiologia , Rabdomiossarcoma/terapia , Neoplasias Vaginais/diagnóstico , Neoplasias Vaginais/cirurgia
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