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1.
Front Neurol ; 12: 638473, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630268

RESUMO

Background: T follicular helper cells (Tfh cells) play an important role in activating B lymphocytes and may associate with idiopathic Optic Neuritis (ON) and Neuromyelitis Optica Spectrum Disorders (NMOSD). Objective: This study aimed to examine the potential role of Tfh cells in pathogenesis of idiopathic ON and NMOSD. Methods: Circulating CD4+CXCR5+ and CD4+CXCR5+PD-1+ cells in 46 idiopathic ON and 68 NMOSD patients as well as 28 healthy controls were examined by flow cytometry before treatment. Serum AQP4 antibody, Expended Disability Status Scale (EDSS) and Visual Outcome Scale (VOS) were detected before and after treatment. Results: The percentages of circulating CD4+CXCR5+ and CD4+CXCR5+PD-1+Tfh cells in CD4+ cells (%) were significantly increased in idiopathic ON and NMOSD compared with those of healthy controls (p < 0.01). No significant difference of Tfh cells in blood and cerebral spinal fluid (CSF) was found between ON and NMOSD patients. The percentages of CSF, CD4+, CXCR5+, and CD4+CXCR5+PD-1+ cells in CD4+ cells (%) were positively correlated with those of the blood (r = 0.5781, r = 0.6079, p = 0.0076, and p = 0.0045, respectively). EDSS scores of NMOSD group were higher than those of ON group and the time course of NMOSD patients was longer than that of ON patients (p < 0.01). After methylprednisolone treatment, both EDSS and VOS scores were significantly decreased at discharge compared with before treatment (p < 0.01). There was no significant correlation among Tfh cell percentages in CD4+ cells, CSF leukocytes, CSF protein, annual recurrence rate, EDSS and VOS scores between two groups (p > 0.05). Conclusion: The Circulating T follicular helper cells were increased in both idiopathic ON and NMOSD.

2.
Front Nutr ; 8: 751627, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631776

RESUMO

The extent of retrogradation strongly affects certain physical and cooking properties of rice starch (RS), which are important to consumers. In this study, oligomeric procyanidins from lotus seedpod (LSOPC) was prepared and used to investigate its inhibitory effect on RS retrogradation. Various structural changes of RS during retrogradation were characterized by differential scanning calorimetry, low field nuclear magnetic resonance, X-ray diffraction, scanning electron microscopy, and Fourier transform infrared spectroscopy. The results showed LSOPC could effectively retard both short- and long-term retrogradation of RS, and its inhibitory effect was dependent on the administered concentration of LSOPC. Molecule simulation revealed the interactions of RS and LSOPC, which indicated that the competition of hydrogen bonds between RS and LSOPC was the critical factor for anti-retrogradation. This inhibitory effect and mechanism of action of LSOPC could promote its applications in the field of starch anti-retrogradation.

3.
Medicine (Baltimore) ; 100(39): e27387, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596161

RESUMO

RATIONALE: Tuberculosis (TB) is one of the top 10 causes of death worldwide and is the leading infectious cause of death. The incidence of TB, especially active TB, is increased in pregnant and postpartum women. Newborns can be infected with TB from their mothers through several routes. Diagnosis of TB in pregnant women and infants is difficult. Here, we report the simultaneous postdelivery diagnosis of TB in a mother and infant pair. PATIENT CONCERNS: A 28-year-old woman presented with a sudden onset of convulsions, loss of consciousness, coughing, fever, and breathing difficulty. Her 18-day-old infant daughter developed cough and wheezing. DIAGNOSIS: The mother's chest computed tomography showed diffuse interstitial changes and both lungs' exudation. Enhanced cranial magnetic resonance imaging showed scattered nodular intracranial lesions. A tuberculin skin test and an interferon-gamma release assay were negative. Xpert MTB/RIF (Xpert) testing and acid-fast bacilli smear of bronchoalveolar lavage (BAL) fluid of the mother were negative. Loop-mediated isothermal amplification of BAL fluid was positive for Mycobacterium tuberculosis, and next-generation sequencing confirmed the diagnosis of TB. A biopsy specimen also showed characteristic TB findings. The mother was diagnosed with TB and TB encephalitis. The infant's BAL fluid was positive for acid-fast bacilli and Xpert and, therefore, was diagnosed with TB. INTERVENTIONS: The mother was treated with rifampicin and isoniazid for 9 months, ethambutol and pyrazinamide for 3 months, and prednisolone acetate for 8 weeks. The infant received ventilator-assisted ventilation for 10 days and anti-tuberculous therapy for 11 months. OUTCOMES: After anti-tuberculous therapy, the mother and infant both gradually recovered. The mother's chest computed tomography showed significant recovery 9 months after discharge. The infant developed normally during the 11-month follow-up. LESSONS: This mother-child case pair highlights the value of loop-mediated isothermal amplification and next-generation sequencing as new diagnostic technologies for diagnosing TB in patients with multiple negative tests.


Assuntos
Mycobacterium tuberculosis/genética , Tuberculose Pulmonar/diagnóstico , Adulto , Antibióticos Antituberculose/uso terapêutico , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Recém-Nascido , Isoniazida/uso terapêutico , Mycobacterium tuberculosis/isolamento & purificação , Técnicas de Amplificação de Ácido Nucleico , Rifampina/uso terapêutico , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia
4.
Materials (Basel) ; 14(19)2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34640227

RESUMO

This paper presents a new modification of the nanostructure of CaSO4·2H2O crystals containing nanopores. This nanoporous structure was achieved in phosphogypsum samples that were modified by sodium carbonate and alum. The effects of sodium carbonate and alum on the properties of phosphogypsum were studied. X-ray diffraction (XRD) and scanning electron microscopy (SEM) methods were used to explore the micro-mechanism of the composite system. Subsequently, molecular dynamics simulations were used to study the nanopore structures of the modified CaSO4·2H2O. The results show that the addition of sodium carbonate and alum reduced the absolute dry density by 23.1% compared with the original phosphogypsum sample, with a bending strength of 2.1 MPa and compressive strength of 7.5 MPa. In addition, new hydration products, sodium sulfate and sodium aluminum sulfate, were formed in the sample doped with sodium carbonate and alum. A new nanostructure of CaSO4·2H2O crystal containing nanopores was formed. Molecular simulations show that the hydration products were responsible for the surface nanopore formation, which was the main factor leading to an increase in mechanical strength. The presented nanopore structure yields lightweight and high strength properties in the modified phosphogypsum.

5.
Nat Plants ; 7(10): 1335-1346, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34621047

RESUMO

Plants live as sessile organisms with large-scale gene duplication events and subsequent paralogue divergence during evolution. Notably, plant paralogues are expressed tissue-specifically and fine-tuned by phytohormones during various developmental processes. The coat protein complex II (COPII) is a highly conserved vesiculation machinery mediating protein transport from the endoplasmic reticulum to the Golgi apparatus in eukaryotes1. Intriguingly, Arabidopsis COPII paralogues greatly outnumber those in yeast and mammals2-6. However, the functional diversity and underlying mechanism of distinct COPII paralogues in regulating protein endoplasmic reticulum export and coping with various adverse environmental stresses are poorly understood. Here we characterize a novel population of COPII vesicles produced in response to abscisic acid, a key phytohormone regulating abiotic stress responses in plants. These hormone-induced giant COPII vesicles are regulated by an Arabidopsis-specific COPII paralogue and carry stress-related channels/transporters for alleviating stresses. This study thus provides a new mechanism underlying abscisic acid-induced stress responses via the giant COPII vesicles and answers a long-standing question on the evolutionary significance of gene duplications in Arabidopsis.

6.
Transplant Cell Ther ; 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34644605

RESUMO

BACKGROUND: Consolidative hematopoietic cell transplantation (HCT) after CD19 chimeric antigen receptor (CAR) T cell therapy is frequently performed for patients with refractory/relapsed B cell acute lymphoblastic leukemia (B-ALL). However, there is controversy regarding the role of HCT following remission attainment. OBJECTIVES: We evaluated the effect of consolidative HCT on leukemia-free survival (LFS) in pediatric and young adult subjects following CD19 CAR T cell induced remission. STUDY DESIGN: We evaluated the effect of consolidative HCT on leukemia-free survival (LFS) in pediatric and young adult subjects treated with a 41BB-CD19 CAR T cell product on a Phase 1/2 trial, Pediatric and Young Adult Leukemia Adoptive Therapy (PLAT)-02 (NCT02028455), using a time-dependent Cox proportional hazards statistical model. Fifty of 64 subjects enrolled onto PLAT-02 Phase 1 and early Phase 2 were evaluated, excluding 14 subjects who did not achieve remission, relapsed or died prior to day 63 post-CAR T cell therapy. RESULTS: An improved LFS (P=0.01) was observed in subjects who underwent consolidative HCT after CAR T cell therapy versus watchful waiting. Consolidative HCT improved LFS specifically in subjects who had no prior history of HCT, with a trend towards significance (P=0.09). This benefit was not evident when restricted to the cohort of 34 subjects with a history of a prior HCT (P=0.45). However, for subjects who had CAR T cell functional persistence of 63 days or less, inclusive of those with a history of prior HCT, HCT significantly improved LFS outcomes (P=0.01). CONCLUSIONS: These data support consolidative HCT following CD19 CAR T cell-induced remission for patients with no prior history of HCT or for those with short functional CAR T cell persistence.

8.
Acta Pharm Sin B ; 11(9): 2738-2748, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34589394

RESUMO

Synthetic lethality is a proven effective antitumor strategy that has attracted great attention. Large-scale screening has revealed many synthetic lethal genetic phenotypes, and relevant small-molecule drugs have also been implemented in clinical practice. Increasing evidence suggests that CDKs, constituting a kinase family predominantly involved in cell cycle control, are synthetic lethal factors when combined with certain oncogenes, such as MYC, TP53, and RAS, which facilitate numerous antitumor treatment options based on CDK-related synthetic lethality. In this review, we focus on the synthetic lethal phenotype and mechanism related to CDKs and summarize the preclinical and clinical discoveries of CDK inhibitors to explore the prospect of CDK inhibitors as antitumor compounds for strategic synthesis lethality in the future.

9.
Front Psychiatry ; 12: 678594, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34526917

RESUMO

Protracted alcohol withdrawal symptoms (PAWS), characterized by the presence of substance-specific signs and symptoms (including anxiety, irritability, mood instability, insomnia, and cravings), make alcohol abstinence difficult and increase the risk of relapse in recovering alcoholics. The goal of this study was to evaluate the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on PAWS and plasma brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and leptin levels in patients with alcohol dependency. A total of 114 patients with alcohol dependence were randomly divided into two groups: the treatment group and the control group. The patients in the treatment group were treated with taVNS of the bilateral auricular concha using an ear vagus nerve stimulator. The Pennsylvania Alcohol Craving Scale was used to evaluate the extent of craving for alcohol. The Self-Rating Anxiety Scale and Self-Rating Depression Scale (SDS) were used to evaluate the extent of anxiety and depression symptoms, respectively. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. Enzyme-linked immunosorbent assay was used to measure plasma BDNF, IL-6, TNF-α, and leptin levels. The results showed that the SDS and PSQI scores were significantly lower in the treatment group than in the control group. Moreover, compared with the control group, the average BDNF levels in the treatment group were significantly increased. These results suggest that taVNS could improve the depression symptoms and sleep quality in alcohol-dependent patients after withdrawal, which might be related to the upregulation of plasma BDNF levels.

10.
Front Microbiol ; 12: 723152, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34526979

RESUMO

Background: The dysbiosis of respiratory microbiota plays an important role in asthma development. However, there is limited information on the changes in the respiratory microbiota and how these affect the host during the progression from acute allergic inflammation to airway remodeling in asthma. Objective: An ovalbumin (OVA)-induced mouse model of chronic asthma was established to explore the dynamic changes in the respiratory microbiota in the different stages of asthma and their association with chronic asthma progression. Methods: Hematoxylin and eosin (H&E), periodic acid-schiff (PAS), and Masson staining were performed to observe the pathological changes in the lung tissues of asthmatic mice. The respiratory microbiota was analyzed using 16S rRNA gene sequencing followed by taxonomical analysis. The cytokine levels in bronchoalveolar lavage fluid (BALF) specimens were measured. The matrix metallopeptidase 9 (MMP-9) and vascular endothelial growth factor (VEGF-A) expression levels in lung tissues were measured to detect airway remodeling in OVA-challenged mice. Results: Acute allergic inflammation was the major manifestation at weeks 1 and 2 after OVA atomization stimulation, whereas at week 6 after the stimulation, airway remodeling was the most prominent observation. In the acute inflammatory stage, Pseudomonas was more abundant, whereas Staphylococcus and Cupriavidus were more abundant at the airway remodeling stage. The microbial compositions of the upper and lower respiratory tracts were similar. However, the dominant respiratory microbiota in the acute inflammatory and airway remodeling phases were different. Metagenomic functional prediction showed that the pathways significantly upregulated in the acute inflammatory phase and airway remodeling phase were different. The cytokine levels in BALF and the expression patterns of proteins associated with airway remodeling in the lung tissue were consistent with the metagenomic function results. Conclusion: The dynamic changes in respiratory microbiota are closely associated with the progression of chronic asthma. Metagenomic functional prediction indicated the changes associated with acute allergic inflammation and airway remodeling.

11.
Ann Transl Med ; 9(15): 1243, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34532380

RESUMO

Background: The expression profile of lncRNAs in coronary artery disease (CAD) patients has not yet been fully explored. Therefore, the current study aimed to investigate lncRNA-based prognostic biomarkers for CAD. Methods: The expression profiles of lncRNA and messenger RNA (mRNA) were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed lncRNA (DElncRNAs) and DEmRNAs were identified from CAD and normal samples, and weighted gene co-expression network analysis (WGCNA) was conducted. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to investigate the principal functions of significantly dysregulated genes. The potential drugs of new CAD-specific genes were identified by network distance method. Receiver operating characteristic (ROC) was used to verify the classification performance of genes. Results: A total of 512 differentially expressed genes (DEGs) and 308 DElncRNAs were identified from GSE113079 dataset to classify CAD samples. Through WGCNA co-expression analysis, 24 co-expression modules were obtained. A total of 187 DElncRNAs and 253 DEGs were determined from 7 modules correlated with CAD. Functional enrichment analysis showed that these DEGs were mainly related to inflammatory and immune-related pathways. Furthermore, 36 regulatory pairs of significantly shared micro RNAs (miRNAs) were identified as dysregulated lncRNA-mRNA (LRM-CAD), which contained 11 lncRNAs and 33 genes. Compared with a single lncRNA or gene, LRM-CAD showed stronger classification performance [average area under the curve (AUC) =0.958]. We screened 3 potential therapeutic drugs, DB09105, DB12371, and DB12612, a by binding drug-target gene interaction network. Molecular docking verified that the S1PR1 gene bound relatively closely to DB12371 and DB12612. The ROC analysis on external data sets showed that S1PR1, AC012640.4, and S1PR1-AC012640.4 could effectively distinguish CAD samples from control samples. Conclusions: We provided a transcriptome overview of abnormally expressed lncRNAs in CAD patients and identified novel biomarkers for diagnosing CAD.

12.
Mitochondrial DNA B Resour ; 6(10): 2872-2879, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34532575

RESUMO

Phalaenopsis zhejiangensis is a rare and endangered plant species with extremely small populations. The complete chloroplast (cp) genome of P. zhejiangensis was assembled, its structural organization was described and comparative genomic analyses was carried out. The cp genome of P. zhejiangensis is 143,547 bp in length, with a GC content of 37.2%, which includes a pair of inverted repeats (IRs) of 24,464 bp separated by a small single-copy region of 10,764 bp and a large single-copy region of 83,856 bp. The cp genome contains 126 genes, consisting of 80 protein-coding genes, 38 transfer RNAs, and eight ribosomal RNAs. Six protein-coding genes, including ψndhB (two copies), ψndhD, ψndhG, ψndhK, and ψndhI, are identified as pseudogenes. Another six ndh genes, ndhA, ndhC, ndhE, ndhF, ndhH, and ndhJ, are missing from the plastid genome. A total of 41 cp simple sequence repeats (SSRs) were identified, including 40 mono-nucleotides and one di-nucleotides. Phylogenic analysis revealed P. zhejiangensis was nested inside the Phalaenopsis species and sister to P. wilsonii. The assembly and analysis of P. zhejiangensis cp genome will provide essential data for further study of taxonomy and systematics of Orchidaceae.

13.
Biomed Res Int ; 2021: 2202888, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513987

RESUMO

The proliferation of pulmonary artery smooth muscle cells (PASMCs) is an important cause of pulmonary vascular remodeling in pulmonary hypertension (PH). It has been reported that miR-137 inhibits the proliferation of tumor cells. However, whether miR-137 is involved in PH remains unclear. In this study, male Sprague-Dawley rats were subjected to 10% O2 for 3 weeks to establish PH, and rat primary PASMCs were treated with hypoxia (3% O2) for 48 h to induce cell proliferation. The effect of miR-137 on PASMC proliferation and calpain-2 expression was assessed by transfecting miR-137 mimic and inhibitor. The effect of calpain-2 on PASMC proliferation was assessed by transfecting calpain-2 siRNA. The present study found for the first time that miR-137 was downregulated in pulmonary arteries of hypoxic PH rats and in hypoxia-treated PASMCs. miR-137 mimic inhibited hypoxia-induced PASMC proliferation and upregulation of calpain-2 expression in PASMCs. Furthermore, miR-137 inhibitor induced the proliferation of PASMCs under normoxia, and knockdown of calpain-2 mRNA by siRNA significantly inhibited hypoxia-induced proliferation of PASMCs. Our study demonstrated that hypoxia-induced downregulation of miR-137 expression promoted the proliferation of PASMCs by targeting calpain-2, thereby potentially resulting in pulmonary vascular remodeling in hypoxic PH.


Assuntos
Calpaína/genética , Hipertensão Pulmonar/genética , MicroRNAs/genética , Animais , Calpaína/metabolismo , Hipóxia Celular/genética , Hipóxia Celular/fisiologia , Movimento Celular/genética , Proliferação de Células/genética , Células Cultivadas , Hipertensão Pulmonar/patologia , Hipóxia/genética , Hipóxia/metabolismo , Masculino , MicroRNAs/metabolismo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/fisiologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/fisiologia , Artéria Pulmonar/metabolismo , Artéria Pulmonar/fisiologia , Ratos , Ratos Sprague-Dawley , Remodelação Vascular/genética
14.
Pharmacol Res ; 173: 105879, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34508810

RESUMO

Growth arrest and DNA damage-inducible 45ß (GADD45ß) belongs to the GADD45 family which is small acidic proteins in response to cellular stress. GADD45ß has already been reported to have excellent capabilities against cancer, innate immunity and neurological diseases. However, there is little information regard GADD45ß and non-alcoholic fatty liver disease (NAFLD). In the current work, we found that the expression of GADD45ß was markedly decreased in the livers of NAFLD patients via analyzing Gene Expression Omnibus (GEO) dataset and in mouse model through detecting its mRNA in high-fat-high-fructose diet (HFHFr)-fed mice. Moreover, the results from in vivo experiment demonstrated that overexpression of GADD45ß by AAV8-mediated gene transfer in HFHFr-fed mouse model could reduce the level of serum and hepatic triglyceride (TG), and alleviate insulin resistance. Subsequently, by combining immunoprecipitation (IP) and mass spectrometry, we identified that HSP72 directly interacted with GADD45ß to prevent GADD45ß from being degraded by the proteasome pathway. Finally, the benefits of GADD45ß in regulating key factors of TG synthesis and insulin signaling pathway were abolished after HSP72 knockdown. In conclusion, GADD45ß stabilized by the interaction with HSP72 could alleviate the NAFLD-related pathologies, suggested it might be a potential target for the treatment of NAFLD.

15.
Water Res ; 205: 117667, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34547698

RESUMO

Ferrate(VI) (Fe(VI)) can oxidize individual pollutants, but the pollutant oxidation does not necessarily result in toxicity reduction. Besides, Fe(VI) resultant Fe(III) particles has previously been used to remove heavy metals, but its influence on organic matter and toxicity of wastewater is unknown. This study investigated influence of Fe(VI) on the cytotoxicity and DNA double-strand break (DSB) effects of secondary effluents from wastewater treatment plants to Chinese hamster ovary cells. Adding 5.0 mg/L Fe(VI) as Fe reduced the cytotoxicity and genotoxicity of secondary effluents by 44%-71% and 40%-59%, respectively. The toxicity reduction could be explained by the alleviation of oxidative stress in cells when they were exposed to the Fe(VI)-treated organic matter. Oxidation and coagulation accounted for 60 and 40% of the reductions in cytotoxicity and genotoxicity, demonstrating that both oxidation and coagulation processes can play important roles in reducing toxicity. Molecular weight (MW)-distribution analysis showed that the oxidation process was favored for removing ultraviolet absorbance and fluorescence intensity of organic matter, while the coagulation process removed more dissolved organic carbon (DOC), especially the DOC of fractions with MW < 500 Da. Compared with ferric chloride, the Fe(VI) resultant Fe(III) showed better coagulation performance on organic matter, cytotoxicity and genotoxicity removal, because of the different particle sizes and crystalline structures. This study highlights the benefit of using Fe(VI) in advanced treatment as Fe(VI) reduced the overall toxicity of secondary effluents.

16.
J AAPOS ; 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34582958

RESUMO

We report the clinical features, treatments, and outcomes of 9 infants with glaucoma secondary to congenital fibrovascular pupillary membrane. The clinical features included unilateral low vision, high intraocular pressure (IOP), enlarged and cloudy cornea, loss of anterior chamber, and pupillary membrane. All patients underwent membranectomy, peripheral iridectomy, pupilloplasty, and goniosynechialysis as primary treatment. The membranes were posterior to the iris in all 9 eyes. In 5 eyes, the membrane covered the ciliary processes, and in 1 eye the membrane reached the posterior lens capsule. Following primary surgery, 3 patients developed membrane recurrence, 4 had refractory elevated IOP, and 2 developed lens opacities. All 4 eyes with poor postoperative IOP control had iris root insertion anterior to the scleral spur. Five patients received additional surgeries including membranectomy, pupilloplasty, goniosynechialysis, cyclocryotherapy, ciliary photocoagulation, Amhed valve implantation, and lensectomy. One patient had refractory elevated IOP at last follow-up. IOP in the other 8 eyes was well controlled. None of the affected eyes was able to fix and follow at last follow-up.

17.
Food Funct ; 12(20): 10184-10195, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34532729

RESUMO

Dietary interventions, including dietary ingredients, nutrients and probiotics, exert anti-inflammatory effects in ulcerative colitis (UC). Our previous study showed that Akkermansia muciniphila (Akk), a promising probiotic, could protect against colitis via the regulation of the immune response. However, whether it can restore aberrant tryptophan (Trp) metabolism during colitis remains unclear. In this study, untargeted serum metabolomics of patients with UC and colitis mice showed that Trp metabolism was activated, which was confirmed by quantification of Trp metabolites from a validation cohort and animal study. Integrative analysis of faecal metagenomes and serum metabolomes revealed significant associations between Akk and three Trp metabolites. Live Akk, pasteurised Akk and Amuc_1100 failed to restore the reduction in Trp metabolites involved in the serotonin pathway in colitis mice. However, live Akk, pasteurised Akk and Amuc_1100 increased kynurenine (Kyn) but decreased 2-picolinic acid (PIC) levels and the PIC/Kyn ratio without regulating any of the genes involved in Trp metabolism, suggesting that they could suppress the Kyn pathway (KP) independent of colon tissue. In addition, they could significantly restore the enrichment of Trp metabolism mediated by faecal microbiota. Specifically, live Akk, pasteurised Akk and Amuc_1100 could significantly offset the reduction in indoleacetic acid (IAA) levels. Pasteurised Akk significantly elevated the serum levels of indole acrylic acid (IA). In addition, live Akk, pasteurised Akk and Amuc_1100 could upregulate aryl hydrocarbon receptor (AhR) targeted genes, including CYP1A1, IL-10 and IL-22, suggesting that Akk could activate AhR signaling by regulating Trp metabolism, thereby attenuating colonic inflammation.

18.
Artigo em Inglês | MEDLINE | ID: mdl-34484655

RESUMO

Multi- and hyperspectral imaging modalities encompass a growing number of spectral techniques that find many applications in geospatial, biomedical, machine vision and other fields. The rapidly increasing number of applications requires convenient easy-to-navigate software that can be used by new and experienced users to analyse data, and develop, apply and deploy novel algorithms. Herein, we present our platform, IDCube Lite, an Interactive Discovery Cube that performs essential operations in hyperspectral data analysis to realise the full potential of spectral imaging. The strength of the software lies in its interactive features that enable the users to optimise parameters and obtain visual input for the user in a way not previously accessible with other software packages. The entire software can be operated without any prior programming skills allowing interactive sessions of raw and processed data. IDCube Lite, a free version of the software described in the paper, has many benefits compared to existing packages and offers structural flexibility to discover new, hidden features that allow users to integrate novel computational methods.

19.
J Hazard Mater ; 416: 126198, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492962

RESUMO

Natural organic matter is a major source of precursors of hazardous chlorinated disinfection byproducts (Cl-DBPs) formed during water treatment, but the majority of Cl-DBPs are still unidentified. In this study, we used a self-written halogen extraction code to identify halogen isotopic patterns in combination with the R package MFAssignR, to identify Cl-DBPs from Orbitrap mass spectra. One hundred and eighty-nine Cl-DBPs were detected during chlorination of a Suwannee River natural organic matter solution, and the structures of 20 of these compounds are reported for the first time. Kendrick mass defect analysis and structural identification confirmed that chlorinated carboxylic acids are common and likely to form during chlorination. A toxicity prediction using quantitative structure-activity relationship models indicated that most of the chlorinated carboxylic acids may be highly toxic. Our analytical strategy can identify Cl-DBPs accurately from complex mixtures and may also be applicable to the identification of other halogenated disinfection byproducts formed during water treatment.


Assuntos
Desinfetantes , Poluentes Químicos da Água , Purificação da Água , Desinfecção , Halogenação , Halogênios , Espectrometria de Massas , Poluentes Químicos da Água/análise
20.
J Clin Pharm Ther ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34544199

RESUMO

WHAT IS KNOWN AND OBJECTIVE: As an oral hypoglycaemic drug that significantly reduces cardiovascular risk, empagliflozin is often used in patients with type 2 diabetes mellitus (T2DM). However, the dosage and administration of empagliflozin are still controversial clinically. To determine the most appropriate dose, we performed this network meta-analysis. METHODS: We identified randomized controlled trials (RCTs) about empagliflozin from eight databases. We analysed the pharmacodynamics, adverse effects (AEs), and pharmacokinetics of empagliflozin at different doses. RESULTS: We identified 8264 articles, of which 23 RCTs with 10518 patients were included. Regarding haemoglobin A1c (HbA1c) and fasting plasma glucose (FPG), high-daily doses (10, 25, 50 mg) were significantly better than low doses (1, 2.5, 5 mg). For total AEs, there was a dose-response trend in which safety decreased with increasing doses. According to SUCRA sequencing, the order for lowering HbA1c was 25 > 50 > 10 > 5 > 1 mg, for lowering FPG was 50 > 25 > 10 > 5 > 2.5 > 1 mg and for safety was 1> 5 > 10 > 25> 2.5 > 50 mg. When considering HbA1c, FPG and total AEs, we performed a hierarchical cluster analysis and network meta-analysis to find that 25 mg performed best among different doses, which was more significant after long-term use (≥ 12 weeks). Pharmacokinetic parameters exhibited significant dose-response relationships. WHAT IS NEW AND CONCLUSION: High-daily doses (10, 25, 50 mg) had better efficacy than low doses (1, 2.5, 5 mg). When considering HbA1c, FPG and total AEs, 25 mg performed best among the different doses in patients with T2DM.

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