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1.
IEEE Trans Cybern ; PP2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34613927

RESUMO

In nonstationary environments, data distributions can change over time. This phenomenon is known as concept drift, and the related models need to adapt if they are to remain accurate. With gradient boosting (GB) ensemble models, selecting which weak learners to keep/prune to maintain model accuracy under concept drift is nontrivial research. Unlike existing models such as AdaBoost, which can directly compare weak learners' performance by their accuracy (a metric between [0, 1]), in GB, weak learners' performance is measured with different scales. To address the performance measurement scaling issue, we propose a novel criterion to evaluate weak learners in GB models, called the loss improvement ratio (LIR). Based on LIR, we develop two pruning strategies: 1) naive pruning (NP), which simply deletes all learners with increasing loss and 2) statistical pruning (SP), which removes learners if their loss increase meets a significance threshold. We also devise a scheme to dynamically switch between NP and SP to achieve the best performance. We implement the scheme as a concept drift learning algorithm, called evolving gradient boost (LIR-eGB). On average, LIR-eGB delivered the best performance against state-of-the-art methods on both stationary and nonstationary data.

2.
Food Funct ; 12(20): 9844-9854, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34664584

RESUMO

The dysbiosis of gut microbiota is closely related to the occurrence and development of inflammatory bowel disease (IBD). The manipulation of intestinal flora through prebiotics or probiotics is expected to induce and maintain the remission of IBD symptoms. 6-week-old C57BL/J mice were daily gavaged with fructooligosaccharides (FOS) or the synbiotic two weeks before the administration of dextran sulfate sodium (DSS). The supplementation of FOS or synbiotic could significantly ameliorate the body weight loss and colon histological damage in DSS-induced acute colitis mice. The altered composition of gut microbiota in acute colitis mice was reversed by FOS or Synbiotic supplementation, with a characteristic of decreased abundance of Mucispirillum. Both FOS and synbiotic mitigated DSS-induced loss of mucus protein (MUC2) and epithelium tight junction proteins (ZO-1, Occluding, Claudin1) in colon mucosa. The expression of pro-inflammatory cytokines (IL-6 and TNF-α) was decreased by FOS or synbiotic treatment, while the expression of Tbx21 and IL-10 was increased. The results suggested that the modulation of gut microbiota by FOS or synbiotic supplementation could decrease the inflammation potential of colonized commensals, which prevented the impairment of the intestinal barrier and induced a regulation of immune response in DSS-induced acute colitis mice.

3.
Theranostics ; 11(19): 9296-9310, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646371

RESUMO

Mutations in serotonin pathway genes, especially the serotonergic receptor subunit gene HTR3A, are associated with autism. However, the association of HTR3A deficiency with autism and the underlying mechanisms remain unknown. Methods: The Htr3a knockout (KO) mice were generated using transcription activator-like effector nuclease technology. Various behavior tests, including social interaction, social approach task, olfactory habituation/dishabituation, self-grooming, novel object recognition, contextual fear conditioning, elevated plus maze, open field and seizure susceptibility, were performed to assess the phenotypes. Transcriptome sequencing was carried out to search for molecular network and pathways underlying the phenotypes. Electrophysiological recordings, immunoblotting, immunofluorescence staining, immunoprecipitation, and quantitative real-time PCR were performed to verify the potential mechanisms. The N-methyl-D-aspartate receptor (NMDAR) antagonist memantine was used to treat the KO mice for rescuing the phenotypes. Results: The Htr3a KO mouse model showed three phenotypic domains: autistic-like behaviors (including impaired social behavior, cognitive deficits, and increased repetitive self-grooming), impaired memory, and attenuated susceptibility to pentylenetetrazol-induced seizures. We observed enhanced action potential-driven γ-aminobutyric acid-ergic (GABAergic) transmission in pyramidal neurons and decreased excitatory/inhibitory (E/I) ratio using the patch-clamp recording. Transcriptome sequencing on the hippocampus revealed the converged pathways of the dysregulated molecular networks underlying three phenotypic domains with upregulation of NMDAR. We speculated that Htr3a KO promotes an increase in GABA release through NMDAR upregulation. The electrophysiological recordings on hippocampal parvalbumin-positive (PV+) interneuron revealed increased NMDAR current and NMDAR-dependent excitability. The NMDAR antagonist memantine could rescue GABAergic transmission in the hippocampus and ameliorate autistic-like behaviors of the KO mice. Conclusion: Our data indicated that upregulation of the NMDAR in PV+ interneurons may play a critical role in regulating GABAergic input to pyramidal neurons and maybe involve in the pathogenesis of autism associated with HTR3A deficiency. Therefore, we suggest that the NMDAR system could be considered potential therapeutic target for autism.

5.
J Cereb Blood Flow Metab ; : 271678X211045222, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34515547

RESUMO

Acute stroke is associated with high morbidity and mortality. In the last decades, new therapies have been investigated with the aim of improving clinical outcomes in the acute phase post stroke onset. However, despite such advances, a large number of patients do not demonstrate improvement, furthermore, some unfortunately deteriorate. Thus, there is a need for additional treatments targeted to the individual patient. A potential therapeutic target is interventions to optimize cerebral perfusion guided by cerebral hemodynamic parameters such as dynamic cerebral autoregulation (dCA). This narrative led to the development of the INFOMATAS (Identifying New targets FOr Management And Therapy in Acute Stroke) project, designed to foster interventions directed towards understanding and improving hemodynamic aspects of the cerebral circulation in acute cerebrovascular disease states. This comprehensive review aims to summarize relevant studies on assessing dCA in patients suffering acute ischemic stroke, intracerebral haemorrhage, and subarachnoid haemorrhage. The review will provide to the reader the most consistent findings, the inconsistent findings which still need to be explored further and discuss the main limitations of these studies. This will allow for the creation of a research agenda for the use of bedside dCA information for prognostication and targeted perfusion interventions.

6.
Int J Med Inform ; 154: 104559, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34474309

RESUMO

BACKGROUND: Blockchain distributed ledger technology is just starting to be adopted in genomics and healthcare applications. Despite its increased prevalence in biomedical research applications, skepticism regarding the practicality of blockchain technology for real-world problems is still strong and there are few implementations beyond proof-of-concept. We focus on benchmarking blockchain strategies applied to distributed methods for sharing records of gene-drug interactions. We expect this type of sharing will expedite personalized medicine. BASIC PROCEDURES: We generated gene-drug interaction test datasets using the Clinical Pharmacogenetics Implementation Consortium (CPIC) resource. We developed three blockchain-based methods to share patient records on gene-drug interactions: Query Index, Index Everything, and Dual-Scenario Indexing. MAIN FINDINGS: We achieved a runtime of about 60 s for importing 4,000 gene-drug interaction records from four sites, and about 0.5 s for a data retrieval query. Our results demonstrated that it is feasible to leverage blockchain as a new platform to share data among institutions. PRINCIPAL CONCLUSIONS: We show the benchmarking results of novel blockchain-based methods for institutions to share patient outcomes related to gene-drug interactions. Our findings support blockchain utilization in healthcare, genomic and biomedical applications. The source code is publicly available at https://github.com/tsungtingkuo/genedrug.

7.
Mol Ther ; 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34547464

RESUMO

N6-methyladenosine (m6A) mRNA modification plays critical roles in various biological events and involves in multiple complex diseases. However, the role of m6A modification in autophagy in nonalcoholic fatty liver disease (NAFLD) remains largely unknown. Here, we report that m6A modification was increased in livers of NAFLD mouse models and in free fatty acids (FFAs)-treated hepatocytes, and the abnormal m6A modification was attributed to the upregulation of methyltransferase like 3 (METTL3) induced by lipotoxicity. Knockdown of METTL3 promoted hepatic autophagic flux and lipid drops (LDs) clearance, while overexpression METTL3 inhibited these process. Mechanistically, METTL3 directly bound to Rubicon mRNA and mediated the m6A modification. While YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), as a partner of METTL3, interacted with the m6A-marked Rubicon mRNA and promoted its stability. Subsequently, RUBICON inhibited autophagosome-lysosome fusion and further blocked LDs clearance. Together, our results showed a critical role of METTL3 and YTHDF1 in regulating lipid metabolism via autophagy pathway and provided a novel insight into m6A mRNA methylation in NAFLD.

8.
Psychophysiology ; : e13949, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34587299

RESUMO

The incidence of depression is increasing, especially in the young adult population. Impaired cognitive function is one of the characteristics of depression, which may be related to impaired cerebral autoregulation (CA). We investigated the characteristics of CA in young adults with mild depression, as well as its validity for identifying patients with depression. Patients (aged 18-35 years) with Hamilton Depression Rating Scale (HAMD) scores ranging from 8 to 17 and a first episode of mild depression were enrolled in this study. Healthy volunteers were recruited as controls. Noninvasive continuous arterial blood pressure and bilateral middle cerebral artery blood flow velocity were simultaneously recorded from each subject. Transfer function analysis was applied to derive phase difference, gain, coherence and rate of recovery for the assessment of CA. Forty-three patients and 43 healthy controls were enrolled. Phase difference values were significantly compromised in young adults with mild depression and were negatively correlated with HAMD scores. Rate of recovery values estimated from depressed patients was significantly lower. The validity in identifying patients with depression was favorable for the phase difference. The cutoff phase difference value was 29.66. Our findings suggest that dynamic CA was impaired in young patients with mild depression and negatively correlated with HAMD scores. CA represented by phase difference can be used as an objective auxiliary examination of depression, and has clinical diagnostic value for the early identification of patients with depression.

9.
AMIA Annu Symp Proc ; 2021: 384-393, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34457153

RESUMO

From electronic health records (EHRs), the relationship between patients' conditions, treatments, and outcomes can be discovered and used in various healthcare research tasks such as risk prediction. In practice, EHRs can be stored in one or more data warehouses, and mining from distributed data sources becomes challenging. Another challenge arises from privacy laws because patient data cannot be used without some patient privacy guarantees. Thus, in this paper, we propose a privacy-preserving framework using sequential pattern mining in distributed data sources. Our framework extracts patterns from each source and shares patterns with other sources to discover discriminative and representative patterns that can be used for risk prediction while preserving privacy. We demonstrate our framework using a case study of predicting Cardiovascular Disease in patients with type 2 diabetes and show the effectiveness of our framework with several sources and by applying differential privacy mechanisms.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Doenças Cardiovasculares/diagnóstico , Confidencialidade , Registros Eletrônicos de Saúde , Humanos , Privacidade
10.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(3): 266-271, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34374239

RESUMO

Objective: To investigate the effect of TGF-ß1/Smad signaling pathway on the apoptosis of HepG2 cells under endoplasmic reticulum stress (ERS). Methods: An ERS model was established firstly. Human hepatocellular carcinoma HepG2 cells were treated with 3 µmol/L tunicamycin (TM) for 24 h to induce ERS. Cells were divided into 6 groups, each with 3 replicate holes, and the experiment was repeated 3 times. The 6 groups included untreated group, TM group (3 µmol/L TM treatment group), TM + NC group(3 µmol/L TM + si-TGF-ß1 negative control group), TM + si-TGF-ß1 group(3 µmol/L TM + si-TGF-ß1 group), TM + pEX-3 group(3 µmol/L TM + plasmid control group), and TM + TGF-ß1 pEX-3 group(3 µmol/L TM + TGF-ß1 overexpressed plasmid group). HepG2 cells were transfected with TGF-ß1 small interfering RNA (TGF-ß1 si-RNA) and TGF-ß1 overexpressed plasmids (TGF-ß1 pEX-3) by Lipofectamine. Twenty-four hours after transfection, RT-qPCR and Western blot were used to detect the expression of TGF-ß1 and p-Smad2 in HepG2 cells of each group. CCK-8 and flow cytometry were used to analyze changes in the proliferation inhibition rate and apoptosis rate of HepG2 cells in each group. Results: Compared with the untreated group, the expressions of TGF-ß1 and p-Smad2 in TM group were significantly reduced (P<0.05). Compared with the TM group, the expressions of TGF-ß1 and p-Smad2, as well as the cell proliferation inhibition rate and apoptosis rate in TM + si-TGF-ß1 group were obviously decreased (P< 0.01), while the expressions of TGF-ß1 and p-Smad2, cell proliferation inhibition rate and apoptosis rate of TM + TGF-ß1 pEX-3 group were significantly increased (P<0.01). Conclusion: The TGF-ß1/Smad signaling pathway was inhibited in hepatocellular carcinoma HepG2 cells under ERS, when this pathway was activated, the apoptosis rate of HepG2 cells under ERS was increased significantly.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Apoptose , Estresse do Retículo Endoplasmático , Células Hep G2 , Humanos , Transdução de Sinais , Fator de Crescimento Transformador beta1
11.
Mol Cancer ; 20(1): 103, 2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-34412652

RESUMO

BACKGROUND: Constitutive activation of nuclear factor-κB (NF-κB) signaling plays a key role in the development and progression of colorectal carcinoma (CRC). However, the underlying mechanisms of excessive activation of NF-κB signaling remain largely unknown. METHODS: We used high throughput RNA sequencing to identify differentially expressed circular RNAs (circRNAs) between normal human intestinal epithelial cell lines and CRC cell lines. The identification of protein encoded by circPLCE1 was performed using LC-MS. The function of novel protein was validated in vitro and in vivo by gain or loss of function assays. Mechanistic results were concluded by immunoprecipitation analyses. RESULTS: A novel protein circPLCE1-411 encoded by circular RNA circPLCE1 was identified as a crucial player in the NF-κB activation of CRC. Mechanistically, circPLCE1-411 promoted the ubiquitin-dependent degradation of the critical NF-κB regulator RPS3 via directly binding the HSP90α/RPS3 complex to facilitate the dissociation of RPS3 from the complex, thereby reducing NF-κB nuclear translocation in CRC cells. Functionally, circPLCE1 inhibited tumor proliferation and metastasis in CRC cells, as well as patient-derived xenograft and orthotopic xenograft tumor models. Clinically, circPLCE1 was downregulated in CRC tissues and correlated with advanced clinical stages and poor survival. CONCLUSIONS: circPLCE1 presents an epigenetic mechanism which disrupts NF-κB nuclear translocation and serves as a novel and promising therapeutic target and prognostic marker.

12.
Biomed Pharmacother ; 142: 111994, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34411921

RESUMO

Secondary hyperparathyroidism (SHPT), the most common complication in the later stage of chronic kidney disease (CKD), seriously affects quality of life and the survival time of patients. At present, the conventional drugs and surgical methods still cannot fully meet the needs of clinical treatment. It is quite significant to develop effective and minimally invasive treatment methods. 5-Aminolevulinic acid-mediated photodynamic therapy (5-ALA-PDT), an alternative treatment relying on light irradiation, photosensitizer, and oxygen to produce a series of cytotoxic effects on tissue, is a promising technique for treating SHPT. We have successfully cultivated SHPT primary cells and organoids, and further proved that the amount of 5-ALA transformed into protoporphyrin IX in a time- and concentration-dependent manner. Also, 5-ALA-PDT exerted a cytotoxic effect on both primary cells and organoids by the cell counting kit (CCK-8) assay. Mechanically, 5-ALA-PDT increased the number of autophagosomes, and autophagy- and apoptosis-related proteins were upregulated markedly by western-blotting. The autophagy inhibitor Chloroquine (CQ) significantly increased the proportion of apoptotic cells, while the autophagy inducer rapamycin decreased the inhibitory ability of 5-ALA-PDT in SHPT primary cells. In brief, 5-ALA-PDT exhibits a phototoxic effect on SHPT primary cells and organoids. Autophagy and apoptosis are involved in the mechanism, and autophagy plays a role in promoting survival and inhibiting apoptosis. Therefore, the use of autophagy inhibitors can increase the sensitivity of SHPT cells and organoids treated with 5-ALA-PDT.

13.
Transl Psychiatry ; 11(1): 374, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34226510

RESUMO

Suffering from COVID-19 and witnessing the suffering and deaths of patients with COVID-19 may place frontline healthcare workers (HCWs) at particularly high risk for posttraumatic stress disorder (PTSD); however, few data are available on the clinical characteristics of PTSD among frontline HCWs who survived COVID-19 ("surviving HCWs" hereafter). The present study examined the prevalence, correlates, and clinical symptoms of possible PTSD in surviving HCWs 6 months after the COVID-19 outbreak in China. A total of 291 surviving HCWs and 42 age- and gender-matched COVID-19-free frontline HCWs (control group) were recruited and administered the Chinese Essen Trauma Inventory, which was used to assess the presence of possible PTSD according to DSM-IV-TR criteria. Survivors' clinical data and characteristics of exposure to COVID-19 were collected via self-report questionnaires. Surviving HCWs had significantly higher rates of possible PTSD than controls (19.9% vs. 4.8%, P = 0.017). Correlates of PTSD in survivors were ICU admission (OR = 8.73, P = 0.003), >10 respiratory symptoms during the most symptomatic period of COVID-19 (OR = 3.08, P = 0.006), the residual symptom of dizziness (OR = 2.43, P = 0.013), the residual symptom of difficult breathing (OR = 2.23, P = 0.027), life in danger due to COVID-19 (OR = 16.59, P = 0.006), and exposure to other traumatic events (OR = 2.94, P = 0.035). Less commonly seen PTSD symptoms in survivors were having nightmares about the event (34.5%), suddenly feeling like they were living through the event suddenly (25.9%), being unable to remember an important part of the event (32.8%), and overalertness (31.0%). Nearly one-fifth of the surviving HCWs had possible PTSD 6 months after the COVID-19 outbreak. Mental health services for this vulnerable population should include periodic screening for PTSD, expanded social support, and, when necessary, psychotherapy and psychopharmacological treatment.


Assuntos
COVID-19 , Transtornos de Estresse Pós-Traumáticos , China/epidemiologia , Surtos de Doenças , Pessoal de Saúde , Humanos , Prevalência , SARS-CoV-2 , Transtornos de Estresse Pós-Traumáticos/epidemiologia
14.
Oxid Med Cell Longev ; 2021: 5546493, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34257807

RESUMO

EGCG, as a dietary-derived antioxidant, has been extensively studied for its beneficial health effects. Nevertheless, it induces the transient increase in ROS and leads to the hormetic extension of lifespan. How exactly biology-benefiting effects with the minimum severe adverse are realized remains unclear. Here, we showed that physiological dose of EGCG could help moderate remission in health side effects exposed to high doses, including shortened lifespan, reduced body size, decreased pharyngeal pumping rate, and dysfunctional body movement in C. elegans. Furthermore, we found this result was caused by the physiological dose of EGCG to block the continued ROS accumulation and triggered acclimation responses after stressor removal. Also, in this process, we observed that EGCG downregulated the key redox protein MEMO-1 to activate the feedback loop of NADPH oxidase-mediated redox signaling. Our data indicates that the feedback signal induced by NADPH oxidase may contribute to the health-protective mechanism of dietary polyphenols in vivo.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34310311

RESUMO

This study aimed to develop a sensitive index from transcranial Doppler (TCD) signals for quantitatively evaluating the effects of long-term external counterpulsation (ECP) treatment on stroke rehabilitation. We recruited 27 patients with unilateral ischemic stroke and a good acoustic window within 7 days of stroke onset. 15 of them received 35 daily 1-hour ECP treatment (ECP group) and the others underwent conventional therapy without ECP treatment (No-ECP group). We monitored blood flow in middle cerebral arteries on both sides by TCD, and analyzed them via discrete wavelet analysis method. The overall changes of National Institutes of Health Stroke Scale (NIHSS) and Barthel Index were assessed. A 'big-wave' phenomenon was observed in TCD signals of patients in ECP group after 35 days' treatment, with significant fluctuation in frequency interval from 0.010 to 0.034 Hz as main feature. A new index, which was denoted as I , was derived from this phenomenon. The I was significantly higher for patients in ECP group than that for patients in No-ECP group after 35-days' treatment ( 0.01). And the I was positively correlated with NIHSS change in ECP group ( ). The new index could be used as an effective indicator for evaluating enhancement of endothelial metabolism and neurogenic activity after long-term ECP treatment.


Assuntos
Isquemia Encefálica , Contrapulsação , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Isquemia Encefálica/diagnóstico , Circulação Cerebrovascular , Humanos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , Ultrassonografia Doppler Transcraniana
16.
World J Pediatr Congenit Heart Surg ; 12(4): 529-534, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34278867

RESUMO

BACKGROUND: Low-dose multidetector computed tomographic angiography (MDCTA) is playing an increasingly larger role in the diagnosis of anomalous pulmonary venous return (APVR). Despite advances in new computed tomographic (CT) techniques with radiation dose reduction, there are limited studies describing radiation dose parameters to allow routine use of cardiac CT in infants and children with APVR. This study compares cardiac CT findings with intraoperative findings and describes comprehensive radiation exposure parameters. METHODS: A retrospective analysis of 27 patients compared MDCTA and intraoperative or cardiac catheterization findings of the pulmonary venous anatomy. RESULTS: A total of 32 MDCTA studies were performed on these 27 patients. Of the 28 studies with subsequent intervention, MDCTA accurately diagnosed the anomalous pulmonary venous anatomy in 27 (96.4%) patients. Narrowing of the pulmonary venous confluence entrance to the coronary sinus was missed on cardiac CT in one patient due to motion artifact, but it was noted intraoperatively. Median estimated effective radiation dose was 0.98 mSv (range: 0.39-3.2 mSv), and mean estimated effective radiation dose was 1.1 ± 0.68 mSv. Median total dose length product (DLP) was 25 mGy cm (range: 10-83 mGy cm), and mean total DLP was 28 ± 18 mGy cm. Median CTDI volume was 3.8 mGy (range: 2.5-14.6 mGy), and mean CTDI volume was 5.0 ± 3.2 mGy. CONCLUSIONS: We conclude that modern cardiac MDCTA is the best imaging modality to guide management in both preintervention and postintervention APVR patients. In this study, we describe comprehensive radiation exposure parameters in infants and children with APVR.

17.
Nanoscale ; 13(25): 11188-11196, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34137408

RESUMO

Dopamine (DA) plays a significant role in the human body and cerebral nervous system, and the accurate and rapid assay of DA is essential for the diagnosis of related diseases. Herein, we proposed a turn-on ratiometric fluorescent DA assay strategy by integrating a specific DA-resorcinol chemical reaction with a multifunctional lanthanide metal-organic framework (Ln-MOF). First, Eu-BTC (1,3,5-benzenetricarboxylic acid) was synthesized and further modified to obtain Cu@Eu-BTC, which simultaneously plays multiple roles such as fluorescence internal standard, nanoreactor, cooperative catalysis effect and color shift enhancement. The Cu@Eu-BTC dispersion-based method exhibits ultra-sensitive (limit of detection, LOD is 0.01 µM) and wide-range linear response (0.04-30 µM) to DA in real serum. More importantly, it has excellent selectivity for DA, even in the presence of epinephrine and norepinephrine analogs. Thus, this method realizes the accurate and precise quantification of DA in serum (recoveries: 98.1%-110.1%, relative standard deviation RSD < 4.6%). Next, Cu@Eu-BTC was prepared into paper microchip, which has good storage stability (RSD < 3.5%, n = 3) in four weeks and achieves point-of-care visual DA assay coupled with smartphone-assisted portable detection device. The MOF paper microchip-based method shows low sample consumption (30 µL), high accuracy and precision for the quantification of DA in serum (recovery of 92.9%-106.2%, RSD < 5.3%), and gets the same assay results as the MOF dispersion-based method (relative error ≤ 6.83%). To our knowledge, this is the first time to propose the catalytic fluorescence turn-on detection strategy of DA based on a MOF paper microchip.


Assuntos
Elementos da Série dos Lantanídeos , Estruturas Metalorgânicas , Dopamina , Corantes Fluorescentes , Humanos , Espectrometria de Fluorescência
18.
Phytomedicine ; 87: 153582, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34091150

RESUMO

BACKGROUND AND PURPOSE: Diosmetin (Dios), a flavonoid compound with multiple pharmacological activities. However, fewer studies have reported its effects on type 2 diabetic mellitus (T2DM). Here, we address the effect of Dios on glucose metabolism and gut microbiota in KK-Ay diabetic mice. METHOD: Wild type C57BL/6 J mice or diabetic KK-Ay mice were treated with vehicle or Dios for one month. The ELISA kit and fluorescence microscope system were respectively employed to the evaluation of serum biochemical indicators and histopathological changes. Liver RNA-Seq and western blot were used to reveal the key signaling pathway. The effects of Dios on gut microbiota was investigated by the 16S rRNA gene sequencing, as well as the relationship between Dios and C. glu on glucose metabolism was explored with the C. glu transplantation. RESULTS: Dios treatment significantly decreased blood glucose and increased serum insulin concentrations. RNA-Seq analysis found that the underlying action mechanism of Dios on T2DM was via modulating glucose metabolism, which was proved by up-regulating IRS/PI3K/AKT signaling pathway to promote glycogen synthesis and GLUT4 translocation. Besides, Dios treatment reshaped the unbalanced gut microbiota by suppressing the ratio of Firmicutes/Bacteroidetes and markedly increasing the richness of C. glu. Moreover, treatment with C. glu and Dios together could markedly ameliorate glucose metabolism by up-regulating IRS/PI3K/AKT signaling pathway to promote glycogen synthesis and GLUT4 translocation. CONCLUSIONS: Dios treatment remarkably ameliorated glucose metabolism in KK-Ay diabetic mice by the regulation of C. glu via IRS/PI3K/AKT signaling pathway and reshaped the unbalanced gut microbiota. Our study provided evidence for the application of Dios to the treatment of T2DM.


Assuntos
Corynebacterium glutamicum/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Flavonoides/farmacologia , Hipoglicemiantes/farmacologia , Animais , Glicemia/metabolismo , Proteínas de Ligação a DNA/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/microbiologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Glicogênio/metabolismo , Insulina/sangue , Insulina/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Ribossômico 16S , Fatores de Transcrição/metabolismo
19.
Medicine (Baltimore) ; 100(24): e26265, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34128857

RESUMO

ABSTRACT: Although evidence for the application of an albumin-bilirubin (ALBI) grading system to assess liver function in hepatocellular carcinoma (HCC) is available, less is known whether it can be applied to determine the prognosis of single HCC with different tumor sizes. This study aimed to address this gap.Here, we enrolled patients who underwent hepatectomy due to single HCC from 2010 to 2014. Analyses were performed to test the potential of the ALBI grading system to monitor the long-term survival of single HCC subjects with varying tumor sizes.A total of 265 participants were recruited. The overall survival (OS) among patients whose tumors were ≤7 cm was remarkably higher than those whose tumors were >7 cm. The Cox proportional hazards regression model identified the tumor differentiation grade, ALBI grade, and maximum tumor size as key determinants of OS. The ALBI grade could stratify the patients who had a single tumor ≤7 cm into 2 distinct groups with different prognoses. The OS between ALBI grades 1 and 2 was comparable for patients who had a single tumor >7 cm.We showed that the ALBI grading system can predict disease outcomes in patients with a single HCC with a tumor size ≤7 cm. However, the ALBI grade may not predict the prognosis of patients with a single tumor >7 cm.


Assuntos
Bilirrubina/sangue , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/mortalidade , Gradação de Tumores/mortalidade , Albumina Sérica/análise , Adulto , Idoso , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/cirurgia , Feminino , Hepatectomia/mortalidade , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos
20.
Chem Commun (Camb) ; 57(55): 6764-6767, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34132270

RESUMO

Inspired by the chemistry and biology of hexahydroxanthones, herein we report an organocatalytic Michael-Michael-Aldol-decarboxylation reaction that provides efficient access to biologically interesting fully substituted hexahydroxanthones bearing six contiguous stereogenic centers from readily accessible materials in acceptable yields (up to 63%) and excellent stereoselectivities (up to 10 : 1 dr and >99% ee). In other words, the reaction efficiently produces three chemical bonds and up to six vicinal stereogenic centers in a one-pot operation. In particular, to our knowledge, this is an asymmetric organocatalytic strategy enabling the first construction of six vicinal stereogenic centers on non-spirocyclic hexahydroxanthone frameworks.

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