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1.
ACS Nano ; 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33909407

RESUMO

Precision loading of nanoclusters in confined spaces, which has been enthusiastically pursued in the scientific realm, is still associated with some mysteries of "how", "when", and "why". Here, we isolated two similar heterometallic cluster-in-cage compounds, [Ag@Cu12S8@Cu4(dpph)6]X (X = OH, SD/AgCu16a and X = PF6, SD/AgCu16b; SD = SunDi), by use of an antigalvanic reaction between organometallic [PhC≡CCu]n and Ph3CSH with elemental silver. Both compounds are formed by fitting an Archimedean Ag@Cu12 cuboctahedral cluster into a Platonic Cu4(dpph)6 tetrahedral cage [dpph = bis(diphenylphosphino)hexane]. The Ag@Cu12 cluster is a hollow cuboctahedral Cu12 cage filled with a central AgI atom, and all eight triangular faces of the Ag@Cu12 cuboctahedron are triply capped by eight S2- ions, four of which in a tetrahedral array further internally pillar four Cu vertices of the outer Cu4(dpph)6 tetrahedron, fixing the cluster in the cage. Both compounds can be deemed as molecular fragments excised from porous nanomaterials filled with discrete nanoclusters, thus providing more details for understanding the confined growth of atomically precise nanoclusters. Electrospray ionization mass spectrometry (ESI-MS) reveals that the AgCu16 cluster is quite stable in CH2Cl2 and can stepwise lose dpph ligand in the gas phase under increased collision energy. This work not only presents a precise aggregation of metal atoms in a confined cavity to form a cluster-in-cage compound but also provides deep insights into the binding and geometry matching between clusters and cages in one entity.

2.
Chem Commun (Camb) ; 57(34): 4158-4161, 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33908477

RESUMO

Herein, a multi-functional nanoplatform (PDA-DTC/Cu-MnO2) was established, which has been employed for MR imaging-guided multi-therapy (CDT, PTT and chemotherapy) for cancer treatment. The in vitro and in vivo results confirmed that the biocompatible nanoplatform could significantly induce tumor cell death and inhibit tumor growth.

3.
Interv Neuroradiol ; : 15910199211007295, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33823620

RESUMO

Management of intracranial stenosis remains controversial. Stenting for intracranial stenosis has been associated with high complication and restenosis rates. Morbidity may be related to the intracranial microcatheter exchange that is required in stent placement after the angioplasty. We present a technique in which we deploy an Neuroform Atlas stent through the lumen of a Gateway balloon microcatheter in order to avoid intracranial microcatheter exchange and the associated morbidity. We discuss advantages and pitfalls of this novel technique.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33824992

RESUMO

BACKGROUND: With the dramatically rapid rate of aging worldwide, the maintenance of cognitive function in old age is a major public health priority. The association between total antioxidant capacity (TAC) of midlife diet and cognitive function in late-life is still unclear. METHODS: The study included 16 703 participants from a prospective cohort study in Singapore. Dietary intakes and selected supplementary use were assessed with a validated 165-item food frequency questionnaires at baseline (1993-1998). Two dietary TACs were calculated from the intake of antioxidant nutrients, the Comprehensive Dietary Antioxidant Index (CDAI) and the Vitamin C Equivalent Antioxidant Capacity (VCEAC). Cognitive function was assessed 20.2 years later using a Singapore-modified version of the Mini-Mental State Examination when subjects were 61-96 years old. Cognitive impairment was defined using education-specific cut-offs. Multivariable logistic regression models were utilized to estimate the associations between dietary TACs, component nutrients and cognitive impairment. RESULTS: A total of 2392 participants (14.3%) were defined to have cognitive impairment. Both CDAI and VCEAC scores were inversely associated with odds of cognitive impairment in a dose-dependent manner. The odds ratio (95% confidence interval; p-trend) comparing the highest with the lowest quartile was 0.84 (0.73, 0.96; p-trend = .003) for the CDAI and 0.75 (0.66, 0.86; p-trend < .001) for the VCEAC. Higher intakes of vitamin C, vitamin E, carotenoids, and flavonoids were all inversely associated with cognitive impairment. CONCLUSIONS: Higher dietary total antioxidant capacity was associated with lower odds of cognitive impairment in later life in a Chinese population in Singapore.

5.
Neuroreport ; 32(7): 596-602, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33850085

RESUMO

Changes in the hippocampus are closely associated with learning and memory in Alzheimer's disease; however, it is not clear which morphological and cellular and subcellular changes are essential for learning and memory. Here, we accurately quantitatively studied the hippocampal microstructure changes in Alzheimer's disease model mice and analyzed the relationship between the hippocampal microstructure changes and learning and memory. Ten-month-old male APP/PS1 transgenic mice and age-matched nontransgenic littermate mice were randomly selected. The spatial learning and memory abilities were assessed using the Morris water maze. The volumes of each layer and numbers of neurons, dendritic spines and oligodendrocytes in the hippocampal subregions were investigated using unbiased stereological techniques. The APP/PS1 transgenic mice showed a decline in hippocampus-dependent spatial learning and memory abilities, smaller volumes of each layer (other than stratum radiatum) and fewer numbers of neurons, dendritic spine synapses and mature oligodendrocytes in the hippocampal subregions than nontransgenic mice. In particular, the decline of spatial learning ability was significantly correlated with the atrophy of lacunosum moleculare layer (LMol) and the decrease of hippocampal neurons and mature oligodendrocytes rather than dendritic spines. The CA1-3 fields (including LMol) atrophy was significantly correlated with the decrease both of neurons, dendritic spines and mature oligodendrocytes. However, the dentate gyrus atrophy was significantly correlated with the decrease of neurons and mature oligodendrocytes rather than dendritic spines. The loss of neurons, dendritic spines synapses and mature oligodendrocytes together caused the LMol atrophy and then led to a decline in hippocampus-dependent spatial learning ability in mice with Alzheimer's disease.

6.
Environ Res ; 197: 111089, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33811867

RESUMO

The completely biological degradation of Tetrabromobisphenol A (TBBPA) contaminant is challenging. Bio-electrochemical systems are efficient to promote electrons transfer between microbes and pollutants to improve the degradation of refractory contaminants. In particular, three-dimensional biofilm electrode reactors (3DBERs), integrating the biofilm with particle electrodes, represent a novel bio-electrochemical technology with superior treatment performances. In this study, the electroactive biofilm is cultured and acclimated on two types of particle electrodes, granular activated carbon (GAC) and granular zeolite (GZ), to degrade the target pollutant TBBPA in 3DBERs. Compared to GZ, GAC materials are more favorable for biofilm formation in terms of high specific surface area and good conductivity. The genus of Thauera is efficiently enriched on both GAC and GZ particles, whose growth is promoted by the electricity. By applying 5 V voltage, TBBPA can be removed by over 95% in 120 min whether packing GAC or GZ particle electrodes in 3DBERs. The synergy of electricity and biofilm in TBBPA degradation was more significant in GAC packed 3DBER, because the improved microbial activity by electrical stimulation accelerates debromination rate and hence the decomposition of TBBPA. Applying electricity also promotes TBBPA degradation in GZ packed 3DBER mainly due to the enhanced electrochemical effects. Roles of particle electrode materials in TBBPA removal are distinguished in this work, bringing new insights into refractory wastewater treatment by 3DBERs.

7.
J Agric Food Chem ; 69(17): 5026-5039, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33902286

RESUMO

This study is aimed at exploring the release of bound polyphenols (BP) from insoluble dietary fiber (IDF) and its mechanism by solid-state fermentation (SSF) via Trichoderma viride. The results indicated that BP released by SSF (5.55 mg GAE/g DW) was significantly higher than by alkaline hydrolysis. In addition, 39 polyphenols and catabolites were detected, and the related biotransformation pathways were speculated. Quantitative analysis showed that SSF released more ferulic acid, p-coumaric acid, and organic acids, which led to advances in antioxidant, α-amylase, and α-glucosidase inhibitory activities. Furthermore, structural characteristics (scanning electron microscopy, X-ray diffraction, thermos gravimetric analysis, and Fourier transform infrared spectroscopy) and dynamic changes of carbohydrate-hydrolyzing enzymes indicated that the destruction of hemicellulose and the secretion of xylanase were vital for releasing BP. Overall, this study demonstrated that SSF was beneficial to release BP from IDF, which could provide insight into utilizing agricultural byproducts in a more natural and economical way.

8.
Biochem Pharmacol ; 188: 114561, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33857491

RESUMO

Major depressive disorder (MDD) is a common, chronic, recurrent disease. The existing drugs are ineffective for approximately half of patients, so the development of antidepressant drugs with novel mechanisms is urgent. Cumulative evidence has shown neuro-inflammation plays a key role in the etiology of major depressive disorder. Clinical studies implicated that bile acids, an important component of gut-brain axis, inhibit neuro-inflammation and mediate the pathophysiology of the MDD. Here, we found that ganoderic acid A (GAA) modulated bile acid receptor FXR (farnesoid X receptor), inhibited brain inflammatory activity, and showed antidepressant effects in the chronic social defeat stress depression model, tail suspension, forced swimming, and sucrose preference tests. GAA directly inhibited the activity of the NLRP3 inflammasome, and activated the phosphorylation and expression of the AMPA receptor by modulating FXR in the prefrontal cortex of mice. If we knocked out FXR or injected the FXR-specific inhibitor z-gugglesterone (GS), the antidepressant effects induced by GAA were completely abolished. These results suggest that GAA modulates the bile acid receptor FXR and subsequently regulates neuroimmune and antidepressant behaviors. GAA and its receptor FXR have potential as targets for the treatment of MDD.

9.
Chin Med J (Engl) ; 134(9): 1079-1086, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33840743

RESUMO

BACKGROUND: The association of lipids and cancer has varied greatly among different cancer types, lipid components and study populations. This study is aimed to investigate the association of serum lipids and the risk of malignant lesions in esophageal squamous epithelium. METHODS: In the "Endoscopic Screening for Esophageal Cancer in China" (ESECC) trial, serum samples were collected and tested for total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol at the time of subject enrollment. Cases were defined as malignant esophageal lesions identified by baseline endoscopic examination or by follow-up to May 31, 2018. Controls were randomly selected using incidence density sampling in the same cohort. Conditional logistic models were applied to identify the association of serum lipids and the risk of malignant esophageal lesions. Effect modification was evaluated by testing interaction terms of the factor under assessment and these serum lipid indicators. RESULTS: No consistent association between serum lipid levels and esophageal malignant lesions were found in a pooled analysis of 211 cases and 2101 controls. For individuals with a family history of esophageal cancer (EC), high TC, and LDL-C were associated with a significantly increased risk of having malignant lesions (odds ratio [OR]High vs. Low TC = 2.22, 95% confidence interval [CI]: 1.14-4.35; ORHigh vs. Low LDL-C = 1.93, 95% CI: 1.01-3.65). However, a negative association was observed in participants without an EC family history (ORHigh vs. Low TC = 0.69, 95% CI: 0.48-0.98, Pinteraction = 0.002; ORHigh vs. Low LDL-C = 0.50, 95% CI: 0.34-0.76, Pinteraction < 0.001). CONCLUSIONS: In this study, we found that the association of serum lipids and malignant esophageal lesions might be modified by EC family history. The stratified analysis would be crucial for population-based studies investigating the association of serum lipids and cancer. The mechanism by which a family history of EC modifies this association warrants further investigation.

10.
Proc Natl Acad Sci U S A ; 118(17)2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33879613

RESUMO

In eukaryotes, secretory proteins traffic from the endoplasmic reticulum (ER) to the Golgi apparatus via coat protein complex II (COPII) vesicles. Intriguingly, during nutrient starvation, the COPII machinery acts constructively as a membrane source for autophagosomes during autophagy to maintain cellular homeostasis by recycling intermediate metabolites. In higher plants, essential roles of autophagy have been implicated in plant development and stress responses. Nonetheless, the membrane sources of autophagosomes, especially the participation of the COPII machinery in the autophagic pathway and autophagosome biogenesis, remains elusive in plants. Here, we provided evidence in support of a novel role of a specific Sar1 homolog AtSar1d in plant autophagy in concert with a unique Rab1/Ypt1 homolog AtRabD2a. First, proteomic analysis of the plant ATG (autophagy-related gene) interactome uncovered the mechanistic connections between ATG machinery and specific COPII components including AtSar1d and Sec23s, while a dominant negative mutant of AtSar1d exhibited distinct inhibition on YFP-ATG8 vacuolar degradation upon autophagic induction. Second, a transfer DNA insertion mutant of AtSar1d displayed starvation-related phenotypes. Third, AtSar1d regulated autophagosome progression through specific recognition of ATG8e by a noncanonical motif. Fourth, we demonstrated that a plant-unique Rab1/Ypt1 homolog AtRabD2a coordinates with AtSar1d to function as the molecular switch in mediating the COPII functions in the autophagy pathway. AtRabD2a appears to be essential for bridging the specific AtSar1d-positive COPII vesicles to the autophagy initiation complex and therefore contributes to autophagosome formation in plants. Taken together, we identified a plant-specific nexus of AtSar1d-AtRabD2a in regulating autophagosome biogenesis.

11.
Aging (Albany NY) ; 13(7): 10688-10702, 2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-33820868

RESUMO

We aimed to explore the mechanism by which long non-coding RNA (lncRNA) OIP5-AS1 affects proNGF (precursor nerve growth factor)-induced pancreatic cancer metastasis by targeting the miR-186-5p/NGFR axis. Bioinformatics was used to analyse whether OIP5-AS1 targets miR-186-5p/NGFR and their expression characteristics in pancreatic cancer. OIP5-AS1 and NGFR were overexpressed in pancreatic cancer, and their levels showed a significant positive correlation. Clinical trials also demonstrated that high expression of OIP5-AS1 and NGFR and low expression of miR-186-5p played a pro-cancer role in pancreatic cancer. MiR-186-5p inhibited the migration and invasion of colon cancer cells by targeting NGFR-regulated p75NTR. OIP5-AS1 regulated the action of miR-186-5p on NGFR mRNA and p75NTR by targeting miR-186-5p. Downregulation of NGFR inhibited the expression of p75NTR protein and blocked the role of proNGF in promoting the migration and invasion of pancreatic cancer cells. Animal experiments also showed that the knockdown of miR-186-5p promoted cancer via the expression of NGFR mRNA and p75NTR protein, while the downregulation of proNGF blocked the effects. OIP5-AS1, as a ceRNA, promotes the progression of pancreatic cancer by targeting miR-186-5p/NGFR and affecting the prognosis of patients, which may be related to the action of proNGF.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33865926

RESUMO

Geriatric depression and anxiety disorders often manifest as neuropsychiatric symptoms among those with mild cognitive impairment. Both tend to co-occur, and overlap in symptomology and etiology. Such commonalities are likely to be reflected in the brain as common neural correlates. Using connectome-based predictive modeling (CPM), we examined the functional and structural connectomes predicting depression and anxiety symptoms, and subsequently the overlap and cross-syndrome generalization of the connectomes associated with either disorder. Ninety-one older adults completed self-reported measures of depression and anxiety, and underwent diffusion tensor imaging and resting-state functional magnetic resonance imaging. Functional connectivity (FC) and structural connectivity (SC) matrices were derived from these scans and, in various combinations, entered into CPM models to predict either type of symptoms. Leave-one-out cross-validation was performed. Predictive accuracy was assessed via the correlation between predicted and observed scores (ρpredicted-observed). While FC or SC features alone significantly predicted either type of symptoms, these symptoms were best predicted by models that consisted of both FC and SC features (depression: ρpredicted-observed = 0.497; anxiety: ρpredicted-observed = 0.455). The features common to depression and anxiety were identified and entered into another model which was similarly accurate in predicting either type of symptoms. Moreover, cross-syndrome generalization was observed- the depression-associated features significantly predicted anxiety symptoms (ρpredicted-observed = 0.403) and vice-versa (ρpredicted-observed = 0.378). These FC and SC features are complementary biomarkers of geriatric depression and anxiety symptoms. Both types of symptoms are largely underpinned by common patterns of altered FC and SC, alluding to the transdiagnostic neurobiological susceptibility in both disorders.

14.
BMJ Open ; 11(3): e043453, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33737431

RESUMO

INTRODUCTION: Blood transfusion is still common in patients undergoing major cancer surgery. Blood transfusion can be associated with poor prognosis in patients with cancer. Perioperative Care in the Cancer Patient -1 (ARCA-1) aims to assess in a large cohort of patients the current incidence, pattern of practice and associations between perioperative blood transfusions and 1-year survival in patients undergoing major cancer surgery. METHODS AND ANALYSIS: ARCA-1 is a prospective international multicentre observational study that will include adult patients scheduled to have major cancer surgical procedures with the intention to cure, and an overnight planned hospital admission. The study will be opened for 1 year for enrolment (7 January 2020-7 February 2021). Each centre will enrol patients for 30 days. The primary endpoint of this study is all-cause mortality 1 year after major cancer surgery. Secondary endpoints are rate of perioperative blood product use, cancer-specific mortality at 1 year and PFSs and 30-day morbidity and mortality. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board at The University of Texas-MD Anderson Cancer Center. The study results will be published in peer-reviewed journals and disseminated at international conferences. TRIAL REGISTRATION NUMBER: NCT04491409.

15.
J Enzyme Inhib Med Chem ; 36(1): 737-748, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33682565

RESUMO

Human Cytochrome P450 2J2 (CYP2J2) as an important metabolic enzyme, plays a crucial role in metabolism of polyunsaturated fatty acids (PUFAs). Elevated levels of CYP2J2 have been associated with various types of cancer, and therefore it serves as a potential drug target. Herein, using a high-throughput screening approach based on enzymic activity of CYP2J2, we rapidly and effectively identified a novel natural inhibitor (Piperine, 9a) with IC50 value of 0.44 µM from 108 common herbal medicines. Next, a series of its derivatives were designed and synthesised based on the underlying interactions of Piperine with CYP2J2. As expected, the much stronger inhibitors 9k and 9l were developed and their inhibition activities increased about 10 folds than Piperine with the IC50 values of 40 and 50 nM, respectively. Additionally, the inhibition kinetics illustrated the competitive inhibition types of 9k and 9l towards CYP2J2, and Ki were calculated to be 0.11 and 0.074 µM, respectively. Furthermore, the detailed interaction mechanism towards CYP2J2 was explicated by docking and molecular dynamics, and our results revealed the residue Thr114 and Thr 315 of CYP2J2 were the critical sites of action, moreover the spatial distance between the carbon atom of ligand methylene and Fe atom of iron porphyrin coenzyme was the vital interaction factor towards human CYP2J2.

16.
Food Chem ; 354: 129528, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-33756320

RESUMO

This study aims to develop novel lutein nanoparticles encapsulized by stevioside (LUT-STE, 165 ± 2 nm average particles size) and systematically evaluate its bioavailability. Multiple spectroscopy and NMR analyses showed lutein and stevioside could interact through hydrogen bonds, CHπ interaction and van der Waals forces. Molecular docking simulation showed lutein was well distributed in the hydrophobic cavity of stevioside. Analyzed by Caco-2 cellular models, the transported amount of LUT-STE was 2.39 times that of lutein in 120 min with a Papp (B â†’ A)/Papp (A â†’ B) value of 0.63 ± 0.04. Nystatin and dynasore significantly reduced the cellular uptake of LUT-STE by 41.3% and 57.7%, respectively. Compared with free lutein, LUT-STE increased the Cmax in mice plasma by 5.01-fold and promoted the accumulation in multiple organs. LUT-STE promoted the protein expressions of CD36, NPC1L1 and PPARγ in both cell and animal models. In conclusion, stevioside entrapment significantly promote the bioavailability of lutein through multiple transmembrane pathways.

17.
Chem Biol Interact ; 340: 109453, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33785314

RESUMO

Gut bacterial ß-glucuronidase (GUS) plays a pivotal role in the metabolism and reactivation of a vast of glucuronide conjugates of both endogenous and xenobiotic compounds in the gastrointestinal tract of human, which has been implicated in certain drug-induced gastrointestinal tract (GI) toxicity in clinic. Inhibitors of gut microbial GUS exhibited great potentials in relieving the drug-induced GI toxicity. In this study, Selaginella tamariscina and its major biflavonoid amentoflavone (AMF) were evaluated for their inhibitory activity against Escherichia coli GUS. Two selective probe substrates for GUS (a specific fluorescent probe substrate for GUS, DDAOG and a classical drug substrate for GUS, SN38G) were used in parallel for charactering the inhibition behaviors. Both the extract of S. tamariscina and its major biflavonoid AMF displayed evident inhibitory effects on GUS, and the IC50 values of AMF against GUS mediated DDAOG and SN-38G hydrolysis were 0.62 and 0.49 µM, respectively. Inhibition kinetics studies indicated that AMF showed mixed type inhibition for GUS-mediated DDAOG hydrolysis, while displayed competitive type inhibition against GUS-mediated SN-38G hydrolysis, with the Ki values of 0.24 and 1.25 µM, respectively. Molecular docking studies and molecular dynamics stimulation results clarified the role of amino acid residues Leu361, Ile363, and Glu413 in the inhibition of AMF on GUS. These results provided some foundations for the potential clinical utility of S. tamariscina and its major biflavonoid AMF for treating drug-induced enteropathy.


Assuntos
Biflavonoides/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Glucuronidase/antagonistas & inibidores , Selaginellaceae/química , Aminoácidos/metabolismo , Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Trato Gastrointestinal/microbiologia , Glucuronídeos/metabolismo , Hidrólise/efeitos dos fármacos , Cinética , Simulação de Acoplamento Molecular/métodos , Simulação de Dinâmica Molecular
18.
JMIR Mhealth Uhealth ; 9(3): e24365, 2021 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-33683207

RESUMO

BACKGROUND: Major depressive disorder (MDD) is a common mental illness characterized by persistent sadness and a loss of interest in activities. Using smartphones and wearable devices to monitor the mental condition of patients with MDD has been examined in several studies. However, few studies have used passively collected data to monitor mood changes over time. OBJECTIVE: The aim of this study is to examine the feasibility of monitoring mood status and stability of patients with MDD using machine learning models trained by passively collected data, including phone use data, sleep data, and step count data. METHODS: We constructed 950 data samples representing time spans during three consecutive Patient Health Questionnaire-9 assessments. Each data sample was labeled as Steady or Mood Swing, with subgroups Steady-remission, Steady-depressed, Mood Swing-drastic, and Mood Swing-moderate based on patients' Patient Health Questionnaire-9 scores from three visits. A total of 252 features were extracted, and 4 feature selection models were applied; 6 different combinations of types of data were experimented with using 6 different machine learning models. RESULTS: A total of 334 participants with MDD were enrolled in this study. The highest average accuracy of classification between Steady and Mood Swing was 76.67% (SD 8.47%) and that of recall was 90.44% (SD 6.93%), with features from all types of data being used. Among the 6 combinations of types of data we experimented with, the overall best combination was using call logs, sleep data, step count data, and heart rate data. The accuracies of predicting between Steady-remission and Mood Swing-drastic, Steady-remission and Mood Swing-moderate, and Steady-depressed and Mood Swing-drastic were over 80%, and the accuracy of predicting between Steady-depressed and Mood Swing-moderate and the overall Steady to Mood Swing classification accuracy were over 75%. Comparing all 6 aforementioned combinations, we found that the overall prediction accuracies between Steady-remission and Mood Swing (drastic and moderate) are better than those between Steady-depressed and Mood Swing (drastic and moderate). CONCLUSIONS: Our proposed method could be used to monitor mood changes in patients with MDD with promising accuracy by using passively collected data, which can be used as a reference by doctors for adjusting treatment plans or for warning patients and their guardians of a relapse. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900021461; http://www.chictr.org.cn/showprojen.aspx?proj=36173.


Assuntos
Transtorno Depressivo Maior , Afeto , Transtorno Depressivo Maior/diagnóstico , Humanos , Aprendizado de Máquina , Estudos Prospectivos , Smartphone
20.
Anal Chim Acta ; 1153: 338305, 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33714444

RESUMO

Human UDP-glucuronosyltransferase enzymes (hUGTs), one of the most important classes of conjugative enzymes, are responsible for the glucuronidation and detoxification of a variety of endogenous substances and xenobiotics. Inhibition of hUGTs may cause undesirable effects or adverse drug-drug interactions (DDI) via modulating the glucuronidation rates of endogenous toxins or the drugs that are primarily conjugated by the inhibited hUGTs. Herein, to screen hUGTs inhibitors in a more efficient way, a novel fluorescence-based microplate assay has been developed by utilizing a fluorogenic substrate. Following screening of series of 4-hydroxy-1,8-naphthalimide derivatives, we found that 4-HN-335 is a particularly good substrate for a panel of hUGTs. Under physiological conditions, 4-HN-335 can be readily O-glucuronidated by ten hUGTs, such reactions generate a single O-glucuronide with a high quantum yield (Ф = 0.79) and bring remarkable changes in fluorescence emission. Subsequently, a fluorescence-based microplate assay is developed to simultaneously measure the inhibitory effects of selected compound(s) on ten hUGTs. The newly developed fluorescence-based microplate assay is time- and cost-saving, easy to manage and can be adapted for 96-well microplate format with the Z-factor of 0.92. We further demonstrate the utility of the fluorescence-based assay for high-throughput screening of two compound libraries, resulting in the identification of several potent UGT inhibitors, including natural products and FDA-approved drugs. Collectively, this study reports a novel fluorescence-based microplate assay for simultaneously sensing the residual activities of ten hUGTs, which strongly facilitates the identification and characterization of UGT inhibitors from drugs or herbal constituents and the investigations on UGT-mediated DDI.

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