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1.
J Affect Disord ; 296: 216-223, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34614438

RESUMO

BACKGROUND: Few studies examining the impact of metabolic syndrome and depressive symptoms on subsequent functional disability are available. OBJECTIVES: To determine the impact of baseline metabolic syndrome and depressive symptoms on subsequent functional disability. METHODS: This study used data from the 2011 baseline and 2013, 2015 and 2018 follow-up waves of the China Health and Retirement Longitudinal Study (CHARLS). Functional status was assessed by activities of daily living (ADLs) and instrumental ADLs (IADLs). Analyses were restricted to middle-aged and older adults (≥50 years) free of functional disability at baseline. Metabolic syndrome, depressive symptoms, and covariates were measured at baseline. New-onset ADL and IADL disability were obtained in follow-up measurements. Competitive risks based on survival analysis were conducted to examine the impact of baseline metabolic syndrome and depressive symptoms on subsequent functional disability after covariates were controlled. RESULTS: Baseline depressive symptoms significantly predicted functional disability over a 7-year follow-up after adjusting for covariates (Hazard ratio [HR] = 1.54, 95% confidence intervals [CI] = 1.40-1.70 for ADL disability; HR=1.36, 95% CI=1.25-1.48 for IADL disability). Metabolic syndrome significantly predicted ADL disability (HR=1.25, 95% CI=1.14-1.38) but not IADL disability (HR=1.02, 95% CI=0.94-1.10). No significant additive interaction between metabolic syndrome and depressive symptoms on functional disability was found. CONCLUSION: The current study found that baseline depressive symptoms were significantly associated with both ADL and IADL disabilities, while metabolic syndrome significantly predicted ADL disability. In addition, some indications showed that the effect in those with both conditions was greater than the sum of the effects separately.

2.
J Ethnopharmacol ; 283: 114456, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34333105

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Hepatocellular carcinoma (HCC) is a liver malignancy which lacks effective treatment and has a poor prognosis. ß-Elemene refers to a natural Curcuma wenyujin-derived single molecular entity, which exhibits various biological activities, and is especially well-known for it's antitumor properties. AIM OF THE RESEARCH: LncRNA HOTAIR, SP1, and PDK1 have displayed oncogenic roles in many tumors, participating in the initiation and progression of cancers by mediating multiple signaling pathways. However, there are only a few reports about their roles and mutual relationship in the growth of HCC cells. Therefore, this study aimed to investigate the expression of LncRNA HOTAIR, SP1, and PDK1 and their interaction with ß-Elemene in HCC cells. MATERIALS AND METHODS: MTT, a Colony formation assay, and flow cytometry were employed to evaluate the growth of HCC and LO2 cells under ß-Elemene. LncRNA HOTAIR, SP1 and PDK1 plasmids were transfected into HCC cells by a transient transfection assay, and the expression and interaction of LncRNA HOTAIR, SP1 and PDK1 were assessed via qRT-PCR and western blotting. RESULTS: ß-Elemene suppressed HCC cell growth through the downregulation of LncRNA HOTAIR, SP1 and PDK1. The results demonstrated a reciprocal interaction among LncRNA HOTAIR, SP1 and PDK1. Exogenous overexpression LncRNA HOTAIR or SP1 eliminated the suppressive effects of ß-Elemene on them, and both of which regulated PDK1 expression in HCC cells. Additionally, exogenously overexpressed SP1 or LncRNA HOTAIR prevented ß-Elemene inhibition of the protein-level expression of PDK1, whereas overexpressing PDK1 had no effect on SP1, though it still weakened the inhibition of cell growth and LncRNA HOTAIR expression by ß-Elemene. CONCLUSION: ß-Elemene suppresses HCC cell proliferation via through the regulation of LncRNA HOTAIR, SP1, PDK1 and their interaction.

3.
Genes (Basel) ; 12(11)2021 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-34828297

RESUMO

Aging is one of the hottest topics in biomedicine. Previous research suggested that ω-3 fatty acids have preventive effects on aging. However, most of previous studies on the anti-aging effects of ω-3 fatty acids are focused on clinical observations, and the anti-aging mechanisms of ω-3 fatty acids have not been fully elucidated. This stimulated our interest to use multi-omics data related to ω-3 fatty acids in order to interpret the anti-aging mechanisms of ω-3 fatty acids. First, we found that ω-3 fatty acids can affect methylation levels and expression levels of genes associated with age-related diseases or pathways in humans. Then, a Mendelian randomization analysis was conducted to determine whether there is a causal relationship between the effect of ω-3 fatty acids on blood lipid levels and variation in the gut microbiome. Our results indicate that the impact of ω-3 fatty acids on aging is partially mediated by the gut microbiome (including Actinobacteria, Bifidobacteria and Streptococcus). In conclusion, this study provides deeper insights into the anti-aging mechanisms of ω-3 fatty acids and supports the dietary supplementation of ω-3 fatty acids in aging prevention.

4.
Biomedicines ; 9(11)2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34829869

RESUMO

The network module-based method has been used for drug repositioning. The traditional drug repositioning method only uses the gene characteristics of the drug but ignores the drug-triggered metabolic changes. The metabolic network systematically characterizes the connection between genes, proteins, and metabolic reactions. The differential metabolic flux distribution, as drug metabolism characteristics, was employed to cluster the agents with similar MoAs (mechanism of action). In this study, agents with the same pharmacology were clustered into one group, and a total of 1309 agents from the CMap database were clustered into 98 groups based on differential metabolic flux distribution. Transcription factor (TF) enrichment analysis revealed the agents in the same group (such as group 7 and group 26) were confirmed to have similar MoAs. Through this agent clustering strategy, the candidate drugs which can inhibit (Japanese encephalitis virus) JEV infection were identified. This study provides new insights into drug repositioning and their MoAs.

5.
Viruses ; 13(11)2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34834924

RESUMO

Over the course of human history, billions of people worldwide have been infected by various viruses. Despite rapid progress in the development of biomedical techniques, it is still a significant challenge to find promising new antiviral targets and drugs. In the past, antiviral drugs mainly targeted viral proteins when they were used as part of treatment strategies. Since the virus mutation rate is much faster than that of the host, such drugs feature drug resistance and narrow-spectrum antiviral problems. Therefore, the targeting of host molecules has gradually become an important area of research for the development of antiviral drugs. In recent years, rapid advances in high-throughput sequencing techniques have enabled numerous genetic studies (such as genome-wide association studies (GWAS), clustered regularly interspersed short palindromic repeats (CRISPR) screening, etc.) for human diseases, providing valuable genetic and evolutionary resources. Furthermore, it has been revealed that successful drug targets exhibit similar genetic and evolutionary features, which are of great value in identifying promising drug targets and discovering new drugs. Considering these developments, in this article the authors propose a host-targeted antiviral drug discovery strategy based on knowledge of genetics and evolution. We first comprehensively summarized the genetic, subcellular location, and evolutionary features of the human genes that have been successfully used as antiviral targets. Next, the summarized features were used to screen novel druggable antiviral targets and to find potential antiviral drugs, in an attempt to promote the discovery of new antiviral drugs.

6.
Sci Rep ; 11(1): 22936, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34824345

RESUMO

This study investigated the outcomes and major adverse cardiovascular events (MACEs) incurred by acute myocardial infarction (AMI) patients comorbiding with hypertension and hyperhomocysteinemia (HHcy) during hospitalization and 1-year follow-up. 648 consecutive AMI patients were divided into four categories: (1) hypertension with Hcy ≥ 15 µmol/L; (2) hypertension with Hcy < 15 µmol/L; (3) no-hypertension with Hcy ≥ 15 µmol/L; (4) no-hypertension with Hcy < 15 µmol/L. Information taken from these case files included gender, past medical history, vital signs, laboratory examination, electrocardiogram, coronary angiography, cardiac ultrasound, and medicine treatment. The primary endpoints were duration of coronary care units (CCU) stay, duration of in-hospital stay, and MACEs during follow-up. Our data show that hypertension and HHcy have a synergistic effect in AMI patients, AMI comorbiding with hypertension and HHcy patients had more severe multi-coronary artery disease and more frequent non-culprit coronary lesions complete clogging, had a higher prevalence of pro-brain natriuretic peptide, and significant decreases in the left ventricular ejection fraction. These patients had significant increases in the duration of CCU stay and in-hospital stay, had significant increase in the rate of MACEs, had significant decreases in the survival rate during follow-up.

7.
Front Plant Sci ; 12: 707127, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804079

RESUMO

Glutathione peroxidases (GPXs) protect cells against damage caused by reactive oxygen species (ROS) and play key roles in regulating many biological processes. Here, five GPXs were identified in the Ricinus communis genome. Phylogenetic analysis displayed that the GPXs were categorized into five groups. Conserved domain and gene structure analyses showed that the GPXs from different plant species harbored four highly similar motifs and conserved exon-intron arrangement patterns, indicating that their structure and function may have been conserved during evolution. Several abiotic stresses and hormone-responsive cis-acting elements existed in the promoters of the RcGPXs. The expression profiles indicated that the RcGPXs varied substantially, and some RcGPXs were coordinately regulated under abiotic stresses. Overexpression of RcGPX4 in Arabidopsis enhanced cold tolerance at seed germination but reduced freezing tolerance at seedlings. The expression of abscisic acid (ABA) signaling genes (AtABI4 and AtABI5), ABA catabolism genes (AtCYP707A1 and AtCYP707A2), gibberellin acid (GA) catabolism gene (AtGA2ox7), and cytokinin (CTK)-inducible gene (AtARR6) was regulated in the seeds of transgenic lines under cold stress. Overexpression of RcGPX4 can disturb the hydrogen peroxide (H2O2) homeostasis through the modulation of some antioxidant enzymes and compounds involved in the GSH-ascorbate cycle in transgenic plants. Additionally, RcGPX4 depended on the MAPK3-ICE1-C-repeat-binding factor (CBF)-COR signal transduction pathway and ABA-dependent pathway to negatively regulate the freezing tolerance of transgenic plants. This study provides valuable information for understanding the potential function of RcGPXs in regulating the abiotic stress responses of castor beans.

8.
Front Oncol ; 11: 750323, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804937

RESUMO

Chidamide has demonstrated significant clinical benefits for patients with relapsed/refractory (R/R) PTCL in previous studies. This multi-center observational study was aimed to evaluate the objective response rate (ORR), overall survival (OS), and safety of chidamide. From February 2015 to December 2017, 548 patients with R/R PTCL from 186 research centers in China were included in the study. Among the 261 patients treated with chidamide monotherapy, ORR was 58.6% and 55 patients (21.1%) achieved complete response (CR). Among the 287 patients receiving chidamide-containing combination therapies, ORR was 73.2% and 73 patients (25.4%) achieved CR. The median OS of all patients was 15.1 months. The median OS of patients receiving chidamide monotherapy and combination therapies was 433 and 463 days, respectively. These results demonstrate a significant survival advantage of chidamide treatments as compared with international historical records. Common adverse effects (AEs) were hematological toxicities. Most AEs in both monotherapy and combined treatments were grade 1-2. No unanticipated AEs occurred. In conclusion, chidamide-based therapy led to a favorable efficacy and survival benefit for R/R PTCL. Future studies should explore the potential advantage of chidamide treatment combined with chemotherapy.

9.
Front Neurosci ; 15: 711528, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34759789

RESUMO

Objective: To investigate the profiles of brain volumetric measurements in children with attention deficit hyperactivity disorder (ADHD), and the consistency of these brain volumetric measurements derived from the synthetic and conventional T1 weighted MRI (SyMRI and cT1w MRI). Methods: Brain SyMRI and cT1w images were prospectively collected for 38 pediatric patients with ADHD and 38 healthy children (HC) with an age range of 6-14 years. The gray matter volume (GMV), white matter volume (WMV), cerebrospinal fluid (CSF), non-WM/GM/CSF (NoN), myelin, myelin fraction (MYF), brain parenchyma volume (BPV), and intracranial volume (ICV) were automatically estimated from SyMRI data, and the four matching measurements (GMV, WMV, BPV, ICV) were extracted from cT1w images. The group differences of brain volumetric measurements were performed, respectively, using analysis of covariance. Pearson correlation analysis and interclass correlation coefficient (ICC) were applied to evaluate the association between synthetic and cT1w MRI-derived measurements. Results: As for the brain volumetric measurements extracted from SyMRI, significantly decreased GMV, WMV, BPV, and increased NON volume (p < 0.05) were found in the ADHD group compared with HC; No group differences were found in ICV, CSF, myelin volume and MYF (p > 0.05). With regard to GMV, WMV, BPV, and ICV estimated from cT1w images, the group differences between ADHD and HC were consistent with the results estimated from SyMRI. And these four measurements showed noticeable correlation between the two approaches (r = 0.692, 0.643, 0.898, 0.789, respectively, p < 0.001; ICC values are 0.809, 0.782, 0.946, 0.873, respectively). Conclusion: Our study demonstrated a global brain development disability, but normal whole-brain myelination in children with ADHD. Moreover, our results demonstrated the high consistency of brain volumetric indices between synthetic and cT1w MRI in children, which indicates the high reliability of SyMRI in the child-brain volumetric analysis.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34772502

RESUMO

Covalent organic frameworks (COFs) have been recognized as a new type of promising visible-light-driven photocatalysts for H2 evolution, while it still is a key point to facilitate the separation and transfer of photoinduced charges for further enhancing their activities. In this work, we fabricated a new type of ternary Pt/rGO/COF photocatalysts with Pt cocatalyst precisely anchored on rGO serving as electron collector for largely enhanced H2 evolution. A series of ternary hybrid materials were obtained via one-pot photoreduction of Pt4+ and GO under visible-light irradiation in a solution the same as photocatalytic H2 evolution reaction and simultaneous self-assembling of rGO/COF heterostructure. No need isolation, the synthetic system could be further used for photocatalytic H2 evolution reaction and the results show the H2 evolution rate of Pt/rGO(20%)/TpPa-1-COF hybrid material is 19.59 mmol·g-1·h-1, 6.51 times higher than that of Pt/TpPa-1-COF. The essential role of the exclusively distributed Pt nanoparticles on rGO to the high H2 evolution activity was confirmed by various comparisons of activity for the samples with diverse Pt distribution.

12.
Anal Chim Acta ; 1184: 338984, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34625268

RESUMO

In this study, Zeolitic Imidazole Framework-8/cellulose aerogel (ZIF-8/CA) hybrid was successfully fabricated through a simple doping method and ZIF-8 acted as the major component for adsorption. In order to elucidate the adsorption mechanism deeply, molecular simulation was adopted to the expound the interaction modes between ZIF-8 and the fluoroquinolones (FQs). ZIF-8/CA was used as the adsorbent for semi-automated pipette tip solid phase extraction (PT-SPE). In combination with high performance liquid chromatography tandem fluorescence detector (HPLC-FLD), the established method was successfully employed to determine trace amount of FQs in water samples. Extraction parameters such as the content of ZIF-8, pH of sample solution, volume of sample, flow rate of sampling, type and volume of elution solvent were investigated. Under the optimized conditions, satisfactory linearity was achieved with the correlation coefficient (R2) ranging from 0.9954 to 0.9992. The limits of detection were in the range of 0.337-1.707 ng L-1. And the recoveries varied from 75.9% to 96.8% with RSD less than 8.0%. The established method was demonstrated to be sensitive, efficient and convenient.


Assuntos
Poluentes Químicos da Água , Zeolitas , Celulose , Fluoroquinolonas/análise , Imidazóis , Extração em Fase Sólida , Água , Poluentes Químicos da Água/análise
14.
Int Immunopharmacol ; 101(Pt B): 108230, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34655850

RESUMO

Maintaining the pulmonary endothelial barrier that prevents the exudation of inflammatory factors and proteins is the key to the treatment of acute lung injury (ALI). Apelin-13 plays an important role in vascular diseases; however, the protective effects of Apelin-13 on ALI with pulmonary endothelial barrier are unknown. Therefore, mice and human umbilical vein endothelial cells (HUVECs) were injured by LPS following Apelin-13 administration. ALI mice showed reduced pulmonary vascular permeability, adhesion junction, mitochondrial function, mitochondrial biogenesis, and autophagy compared to the control group. Apelin-13 administration in ALI mice ameliorated LPS-induced lung injury, pulmonary vascular permeability, mitochondrial function, and promoted autophagic flux in mice and HUVECs. However, the effect of Apelin-13 was reduced after AMPK inhibition using Compound C. These data suggest that Apelin-13 ameliorates pulmonary vascular permeability in mice with ALI induced by LPS, which may be related to enhanced phosphorylation of AMPK to regulate mitochondrial function and autophagy.

15.
J Org Chem ; 86(21): 14640-14651, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34645261

RESUMO

An unprecedented Pd-catalyzed asymmetric intramolecular cascade cyclization of aryl halides with readily available arylboronic acids proceeds through a Heck-type dearomative cyclization terminated with arylation in the presence of Pd2(dba)3 (10 mol %), Cu2O (5 mol %), and Cs2CO3 (2.0 equiv) in 1,2-dichloroethane (1.0 mL) at 100 °C for 15 h in air using BINOL-based phosphoramidite as the chiral ligand. This dearomative Heck protocol, which tolerates a broad variety of functional groups, is amenable to the generation of optically active indoline derivatives bearing all-carbon quaternary stereogenic centers in one step in moderate to excellent yields, with excellent diastereoselectivities (>20:1) and enantioselectivities (up to >99% ee). It is worth mentioning that no decrease in the enantiopurity of the indoline derivatives was observed during the synthetic transformations of the products.

17.
Brain Imaging Behav ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34491528

RESUMO

To investigate the quantitative profiles of brain grey matter (GM) in pediatric drug-naïve ADHD patients using synthetic magnetic resonance imaging (SyMRI). A total of 37 drug-naïve pediatric ADHD and 27 age- and gender-matched healthy controls (HC) were enrolled in this study. Each subject underwent both SyMRI and conventional 3D T1-FSPGR scans. Quantitative parameters, T1 and T2 maps, were extracted from the SyMRI data. Between-group quantitative maps were compared using a general linear model analysis. Pearson correlation analysis was conducted to assess the association between significantly altered MR indices and clinical measurements in ADHD. Compared with the HC group, altered T1 and T2 relaxometry times in the ADHD group were mainly distributed in GM regions of the cerebellum, attention and execution control network, default mode network, and limbic areas. Moreover, the T1 value of the right cerebellum 8 was negatively correlated with the attention concentration level in ADHD (R = 0.140, P = 0.0225). With regards to T2 map, the associations were observed between the attention level of ADHD patients and left fusiform gyrus (R = 0.251, P = 0.0016), and right cerebellum crus2 (R = 0.142, P = 0.0214). Altered T1, T2 values found in specific regions of GM, including cerebellum, attention and execution control network, default mode network, and limbic areas, may reveal widespread micromorphology changes, i.e., brain iron deficiency, low myelin content, and enlarged vascular interstitial space in ADHD patients. Thus, T1, T2 values might be promising imaging markers for future ADHD studies.

18.
Acta Pharmacol Sin ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34480113

RESUMO

Spinal cord injury (SCI) is one kind of severe trauma for central nervous system. Myelin debris clearance and axon regeneration are essential for nerve regeneration after SCI. Metformin, a glucose-lowering drug, has been demonstrated to promote the locomotor functional recovery after SCI. In this study, we investigated the role and molecular mechanism of metformin on myelin preservation in a rat SCI model. SCI was induced in rats by compression at T9 level using a vascular clip. We showed that administration of metformin (50 mg·kg-1·d-1, ip) for 28 days significantly improved locomotor function in SCI rats. Metformin also ameliorated SCI-induced neuronal apoptosis and promoted axon regeneration in the spinal cord. Using co-immunofluorescence of IBa-1 and MBP, and luxol fasting blue (LFB) staining, we demonstrated that metformin promoted the transformation of M1 to M2 phenotype polarization of microglial cells, then greatly facilitated myelin debris clearance and protected the myelin in SCI rats. Furthermore, metformin ameliorated SCI-induced blockade of autophagic flux in the spinal cord, and enhanced the fusion of autophagosome and lysosome by inhibiting the AMPK-mTOR signaling pathway. Moreover, metformin significantly attenuated inflammatory responses in the spinal cord. In LPS-treated BV2 cells, pretreatment with metformin (2 mM) significantly enhanced autophagy level, suppressed inflammation and cell apoptosis. The protective effects were blocked in the presence of an autophagy inhibitor 3-methyladenine (3-MA, 5 mM), suggesting that the effect of metformin on autophagy in microglial cells is essential for the myelin preservation during nerve recovery. This study reveals a novel therapeutic effect of metformin in SCI recovery by regulating the activation of microglial cells and enhancing its autophagy level.

19.
Lab Invest ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521991

RESUMO

Bioactive glass (BG) has recently shown great promise in soft tissue repair, especially in wound healing; however, the underlying mechanism remains unclear. Pyroptosis is a novel type of programmed cell death that is involved in various traumatic injury diseases. Here, we hypothesized that BG may promote wound healing through suppression of pyroptosis. To test this scenario, we investigated the possible effect of BG on pyroptosis in wound healing both in vivo and in vitro. This study showed that BG can accelerate wound closure, granulation formation, collagen deposition, and angiogenesis. Moreover, western blot analysis and immunofluorescence staining revealed that BG inhibited the expression of pyroptosis-related proteins in vivo and in vitro. In addition, while BG regulated the expression of connexin43 (Cx43), it inhibited reactive oxygen species (ROS) production. Cx43 activation and inhibition experiments further indicate that BG inhibited pyroptosis in endothelial cells by decreasing Cx43 expression and ROS levels. Taken together, these studies suggest that BG promotes wound healing by inhibiting pyroptosis via Cx43/ROS signaling pathway.

20.
Genes Dis ; 8(6): 814-826, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34522710

RESUMO

Intestinal cancers are developed from intestinal epithelial stem cells (ISCs) in intestinal crypts through a multi-step process involved in genetic mutations of oncogenes and tumor suppressor genes. ISCs play a key role in maintaining the homeostasis of gut epithelium. In 2009, Sato et al established a three-dimensional culture system, which mimicked the niche microenvironment by employing the niche factors, and successfully grew crypt ISCs into organoids or Mini-guts in vitro. Since then, the intestinal organoid technology has been used to delineate cellular signaling in ISC biology. However, the cultured organoids consist of heterogeneous cell populations, and it was technically challenging to introduce genomic changes into three-dimensional organoids. Thus, there was a technical necessity to develop a two-dimensional ISC culture system for effective genomic manipulations. In this study, we established a conditionally immortalized mouse intestinal crypt (ciMIC) cell line by using a piggyBac transposon-based SV40 T antigen expression system. We showed that the ciMICs maintained long-term proliferative activity under two-dimensional niche factor-containing culture condition, retained the biological characteristics of intestinal epithelial stem cells, and could form intestinal organoids in three-dimensional culture. While in vivo cell implantation tests indicated that the ciMICs were non-tumorigenic, the ciMICs overexpressing oncogenic ß-catenin and/or KRAS exhibited high proliferative activity and developed intestinal adenoma-like pathological features in vivo. Collectively, these findings strongly suggested that the engineered ciMICs should be used as a valuable tool cell line to dissect the genetic and/or epigenetic underpinnings of intestinal tumorigenesis.

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