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1.
Proc Natl Acad Sci U S A ; 119(2)2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-34983871

RESUMO

Late-life ambient air pollution is a risk factor for brain aging, but it remains unknown if improved air quality (AQ) lowers dementia risk. We studied a geographically diverse cohort of older women dementia free at baseline in 2008 to 2012 (n = 2,239, aged 74 to 92). Incident dementia was centrally adjudicated annually. Yearly mean concentrations of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) were estimated using regionalized national universal kriging models and averaged over the 3-y period before baseline (recent exposure) and 10 y earlier (remote exposure). Reduction from remote to recent exposures was used as the indicator of improved AQ. Cox proportional hazard ratios (HRs) for dementia risk associated with AQ measures were estimated, adjusting for sociodemographic, lifestyle, and clinical characteristics. We identified 398 dementia cases during follow up (median = 6.1 y). PM2.5 and NO2 reduced significantly over the 10 y before baseline. Larger AQ improvement was associated with reduced dementia risks (HRPM2.5 0.80 per 1.78 µg/m3, 95% CI 0.71-0.91; HRNO2 0.80 per 3.91 parts per billion, 95% CI 0.71-0.90), equivalent to the lower risk observed in women 2.4 y younger at baseline. Higher PM2.5 at baseline was associated with higher dementia risk (HRPM2.5 1.16 per 2.90 µg/m3, 95% CI 0.98-1.38), but the lower dementia risk associated with improved AQ remained after further adjusting for recent exposure. The observed associations did not substantially differ by age, education, geographic region, Apolipoprotein E e4 genotypes, or cardiovascular risk factors. Long-term AQ improvement in late life was associated with lower dementia risk in older women.

2.
Asian J Pharm Sci ; 16(5): 643-652, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34849169

RESUMO

Disulfide bond-bridging strategy has been extensively utilized to construct tumor specificity-responsive aliphatic prodrug nanoparticles (PNPs) for precise cancer therapy. Yet, there is no research shedding light on the impacts of the saturation and cis-trans configuration of aliphatic tails on the self-assembly capacity of disulfide bond-linked prodrugs and the in vivo delivery fate of PNPs. Herein, five disulfide bond-linked docetaxel-fatty acid prodrugs are designed and synthesized by using stearic acid, elaidic acid, oleic acid, linoleic acid and linolenic acid as the aliphatic tails, respectively. Interestingly, the cis-trans configuration of aliphatic tails significantly influences the self-assembly features of prodrugs, and elaidic acid-linked prodrug with a trans double bond show poor self-assembly capacity. Although the aliphatic tails have almost no effect on the redox-sensitive drug release and cytotoxicity, different aliphatic tails significantly influence the chemical stability of prodrugs and the colloidal stability of PNPs, thus affecting the in vivo pharmacokinetics, biodistribution and antitumor efficacy of PNPs. Our findings illustrate how aliphatic tails affect the assembly characteristic of disulfide bond-linked aliphatic prodrugs and the in vivo delivery fate of PNPs, and thus provide theoretical basis for future development of disulfide bond-bridged aliphatic prodrugs.

3.
J Clin Lab Anal ; : e24164, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34861060

RESUMO

AIMS: The study aimed to investigate the value of autoantibodies in predicting the risk of ketoacidosis or microalbuminuria in children with type 1 diabetes mellitus. METHODS: Clinical data and laboratory indicators of 80 patients with type 1 diabetes admitted to the Department of Endocrinology in Tianjin Children's Hospital, from June 2017 to March 2019, were retrospectively analyzed. The patients were divided into two groups: diabetes without ketoacidosis group (n = 20) and diabetes with ketoacidosis group (n = 60). The differences in general data, laboratory test indexes, and autoantibodies between the two groups were analyzed. Finally, ROC curves and multivariate logistic regression analysis were used to explore the value of autoantibodies in patients with ketoacidosis or microalbuminuria. RESULTS: A total of 80 children with type 1 diabetes were assessed, including 35 boys and 45 girls, ranging in age from 10 months to 15 years. The concentration of GADA, IA2A, and ZnT8A was not statistically different between the two groups, but the positive rate of ZnT8A was statistically significant (p = 0.038) and had a diagnostic value for the occurrence of ketoacidosis (p = 0.025). ZnT8A-positive patients had a higher titer of IA2A and a more frequent prevalence of GADA and IA2A than ZnT8A-negative patients (p < 0.01). In multivariate logistic regression analyses, the presence of positive ZnT8A was associated with a higher risk of microalbuminuria independent of age, sex, and BMI (OR = 4.184 [95% CI 1.034~16.934], p = 0.045). CONCLUSIONS: The positive ZnT8A had diagnostic value for ketoacidosis in children with type 1 diabetes and had the highest specificity among the three kinds of autoantibodies. Moreover, ZnT8A positivity was related to a higher titer of IA2A and more frequent occurrence of multiple diabetes-related autoantibodies. Besides, the presence of positive ZnT8A was an independent risk factor of microalbuminuria in children with type 1 diabetes. Therefore, we can infer that positive ZnT8A may be related to ketoacidosis and microalbuminuria, accelerating the progression of T1DM.

4.
Biomed Pharmacother ; 145: 112475, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34861636

RESUMO

BACKGROUND: Jianpi-Qushi-Heluo formula (JQHF) has been used to treat idiopathic membranous nephropathy (IMN) in hospitals for many years. PURPOSE: Elucidating the protective effect and exploring the potential mechanism of JQHF against IMN. METHODS: Passive Heymann nephritis (PHN) was induced in rats by a single tail vein injection of anti-Fx1A antiserum. Then, the animals were treated with JQHF at 16.2 g/kg or 32.4 g/kg, with benzepril (10 mg/kg) as a positive control. Renal function was evaluated by biochemical measurements and pathological testing. Fecal samples were collected before and after treatment to analyze the gut microbiota composition by shotgun whole metagenome sequencing. RESULTS: JQHF exhibited potent efficacy in ameliorating PHN at both doses, as revealed by decreasing the deposition of IgG and C5b-9, relieving podocyte injury, and reducing glomerular and tubular cell apoptosis. The lower dose was corresponding to the clinical dosage and showed better therapeutic effects than the higher dose. Metagenomic analysis showed that gavage with 16.2 g/kg of JQHF shifted the structure of the gut microbiota in PHN rats and significantly increased the relative abundances of Prevotella copri, Lactobacillus vaginalis and Subdoligranulum variabile. Particularly, S. variabile was strongly negatively correlated with serum levels of TC and TG, the deposition of IgG and C5b-9, and apoptosis of glomerular cells. CONCLUSIONS: The JQHF is an effective agent for the treatment of experimental PHN. The PHN-allevating effect of JQHF is associated with specific alternation of gut microbiota.

6.
J Transl Int Med ; 9(3): 161-167, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34900626

RESUMO

IgA nephropathy (IgAN) is a major cause of chronic kidney disease (CKD) and end-stage renal disease worldwide. Currently, clinical interventions for IgAN are limited, and many patients seek out alternative therapies such as traditional Chinese medicine (TCM). In the last several years, TCM has accumulated ample application experiences and achieved favorable clinical effects. This article summarizes high-quality research from basic science to clinical applications aimed to provide more evidence-based medicine proof for the clinical treatment of IgAN. In summary, qi and yin deficiency accounted for the largest proportion in IgAN patients, and the treatment of IgAN should be based on supplementing qi and nourishing yin. Further, for patients with severe IgAN, the treatment combination of Chinese and Western medicines is better than pure Chinese medicine or hormone therapy. In addition, the pharmacological mechanism of Chinese herbal medicines is mostly based on restoring the immune function, relieving the inflammation damage, and inhibiting proliferation of the glomerular mesangial cells.

7.
Environ Health Perspect ; 129(12): 127008, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34939828

RESUMO

BACKGROUND: Previous studies suggest that certain dietary patterns and constituents may be beneficial to brain health. Airborne exposures to fine particulate matter [particulate matter with aerodynamic diameter ≤2.5µm (PM2.5)] are neurotoxic, but the combined effects of dietary patterns and PM2.5 have not been investigated. OBJECTIVES: We examined whether previously reported association between PM2.5 exposure and lower white matter volume (WMV) differed between women whose usual diet during the last 3 months before baseline was more or less consistent with a Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND)-like diet, a dietary pattern that may slow neurodegenerative changes. METHODS: This study included 1,302 U.S. women who were 65-79 y old and free of dementia in the period 1996-1998 (baseline). In the period 2005-2006, structural brain magnetic resonance imaging (MRI) scans were performed to estimate normal-appearing brain volumes (excluding areas with evidence of small vessel ischemic disease). Baseline MIND diet scores were derived from a food frequency questionnaire. Three-year average PM2.5 exposure prior to MRI was estimated using geocoded participant addresses and a spatiotemporal model. RESULTS: Average total and temporal lobe WMVs were 0.74 cm3 [95% confidence interval (CI): 0.001, 1.48) and 0.19 cm3 (95% CI: 0.002, 0.37) higher, respectively, with each 0.5-point increase in the MIND score and were 4.16 cm3 (95% CI: -6.99, -1.33) and 1.46 cm3 (95% CI: -2.16, -0.76) lower, respectively, with each interquartile range (IQR) (IQR=3.22 µg/m3) increase in PM2.5. The inverse association between PM2.5 per IQR and WMV was stronger (p-interaction<0.001) among women with MIND scores below the median (for total WMV, -12.47 cm3; 95% CI: -17.17, -7.78), but absent in women with scores above the median (0.16 cm3; 95% CI: -3.41, 3.72), with similar patterns for WMV in the frontal, parietal, and temporal lobes. For total cerebral and hippocampus brain volumes or WMV in the corpus callosum, the associations with PM2.5 were not significantly different for women with high MIND scores and women with low MIND scores. DISCUSSION: In this cohort of U.S. women, PM2.5 exposure was associated with lower MRI-based WMV, an indication of brain aging, only among women whose usual diet was less consistent with the MIND-like dietary pattern at baseline. https://doi.org/10.1289/EHP8036.

8.
J Alzheimers Dis ; 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34744078

RESUMO

BACKGROUND: Elucidating associations between exposures to ambient air pollutants and profiles of cognitive performance may provide insight into neurotoxic effects on the aging brain. OBJECTIVE: We examined associations between empirically derived profiles of cognitive performance and residential concentrations of particulate matter of aerodynamic diameter < 2.5 (PM2.5) and nitrogen dioxide (NO2) in older women. METHOD: Women (N = 2,142) from the Women's Health Initiative Study of Cognitive Aging completed a neuropsychological assessment measuring attention, visuospatial, language, and episodic memory abilities. Average yearly concentrations of PM2.5 and NO2 were estimated at the participant's addresses for the 3 years prior to the assessment. Latent profile structural equation models identified subgroups of women exhibiting similar profiles across tests. Multinomial regressions examined associations between exposures and latent profile classification, controlling for covariates. RESULT: Five latent profiles were identified: low performance across multiple domains (poor multi-domain; n = 282;13%), relatively poor verbal episodic memory (poor memory; n = 216; 10%), average performance across all domains (average multi-domain; n = 974; 45%), superior memory (n = 381; 18%), and superior attention (n = 332; 15%). Using women with average cognitive ability as the referent, higher PM2.5 (per interquartile range [IQR] = 3.64µg/m3) was associated with greater odds of being classified in the poor memory (OR = 1.29; 95% Confidence Interval [CI] = 1.10-1.52) or superior attention (OR = 1.30; 95% CI = 1.10-1.53) profiles. NO2 (per IQR = 9.86 ppb) was associated with higher odds of being classified in the poor memory (OR = 1.38; 95% CI = 1.17-1.63) and lower odds of being classified with superior memory (OR = 0.81; 95% CI = 0.67-0.97). CONCLUSION: Exposure to PM2.5 and NO2 are associated with patterns of cognitive performance characterized by worse verbal episodic memory relative to performance in other domains.

9.
Acad Radiol ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34750066

RESUMO

RATIONALE AND OBJECTIVES: Preoperative meningioma consistency prediction is highly beneficial for surgical planning and prognostication. We aimed to use magnetic resonance fingerprinting (MRF)-derived T1 and T2 values to preoperatively predict meningioma consistency. MATERIALS AND METHODS: A total of 51 patients with meningiomas were enrolled in this study. MRF, T1-weighted imaging, T2-weighted imaging, and diffusion-weighted imaging were performed in all patients before surgery using a 3T MRI scanner. MRF-derived T1 and T2 values, T1-weightd and T2-weighted signal intensities, as well as apparent diffusion coefficient value yield from diffusion-weighted imaging were compared between the soft, moderate and hard meningiomas. Receiver operating characteristic curve analyses were used to determine the diagnostic performance of T1, T2 value, and a combination of T1 and T2 values. RESULTS: After Bonferroni corrections, quantitative T1 and T2 values yielded from MRF were significantly different between the soft, moderate and hard meningiomas (all p < 0.05). T2 signal intensity was significantly different between the soft and hard, soft and moderate meningiomas (both p < 0.05), whereas was not significantly different between the moderate and hard meningiomas. However, T1 signal intensity and apparent diffusion coefficient value had no significant differences between the soft, moderate and hard meningiomas (all p > 0.05). The combination of T1 and T2 values had greater areas under receiver operating characteristic curve curves compared to individual T1 or T2 value. CONCLUSION: MRF may help to preoperatively differentiate between the soft, moderate and hard meningiomas and may be useful in guiding the surgical planning.

10.
Front Bioeng Biotechnol ; 9: 726126, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34604186

RESUMO

The compounds 5-aminovalerate and δ-valerolactam are important building blocks that can be used to synthesize bioplastics. The production of 5-aminovalerate and δ-valerolactam in microorganisms provides an ideal source that reduces the cost. To achieve efficient biobased coproduction of 5-aminovalerate and δ-valerolactam in Escherichia coli, a single biotransformation step from L-lysine was constructed. First, an equilibrium mixture was formed by L-lysine α-oxidase RaiP from Scomber japonicus. In addition, by adjusting the pH and H2O2 concentration, the titers of 5-aminovalerate and δ-valerolactam reached 10.24 and 1.82 g/L from 40 g/L L-lysine HCl at pH 5.0 and 10 mM H2O2, respectively. With the optimized pH value, the δ-valerolactam titer was improved to 6.88 g/L at pH 9.0 with a molar yield of 0.35 mol/mol lysine. The ratio of 5AVA and δ-valerolactam was obviously affected by pH value. The ratio of 5AVA and δ-valerolactam could be obtained in the range of 5.63:1-0.58:1 at pH 5.0-9.0 from the equilibrium mixture. As a result, the simultaneous synthesis of 5-aminovalerate and δ-valerolactam from L-lysine in Escherichia coli is highly promising. To our knowledge, this result constitutes the highest δ-valerolactam titer reported by biological methods. In summary, a commercially implied bioprocess developed for the coproduction of 5-aminovalerate and δ-valerolactam using engineered Escherichia coli.

11.
Aging (Albany NY) ; 13(19): 22867-22882, 2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34607974

RESUMO

OBJECT: The present study screened ideal lead natural compounds that could target and inhibit matrix metalloproteinase 9 (MMP9) protein from the ZINC database to develop drugs for clear cell renal cell carcinoma (CCRCC)-targeted treatment. METHODS: Discovery Studio 4.5 was used to compare and screen the ligands with the reference drug, solasodine, to identify ideal candidate compounds that could inhibit MMP9. The LibDock module was used to analyze compounds that could strongly bind to MMP9, and the top 20 compounds determined by the LibDock score were selected for further research. ADME and TOPKAT modules were used to choose the safe compounds from these 20 compounds. The selected compounds were analyzed using the CDOCKER module for molecular docking and feature mapping for pharmacophore prediction. The stability of these compound-MMP9 complexes was analyzed by molecular dynamic simulation. Cell counting kit-8, colony-forming, and scratch assays were used to analyze the anti-CCRCC effects of these ligands. RESULTS: Strong binding to MMP9 was exhibited by 6,762 ligands. Among the top 20 compounds, sappanol and sventenin exhibited nearly undefined blood-brain barrier level and lower aqueous solubility, carcinogenicity, and hepatotoxicity than the positive control drug, solasodine. Additionally, these compounds exhibited lower potential energies with MMP9, and the ligand-MMP9 complexes were stable in the natural environment. Furthermore, sappanol inhibited CCRCC cell migration and proliferation. CONCLUSION: Sappanol and sventenin are safe and reliable compounds to target and inhibit MMP9. Sappanol can CCRCC cell migration and proliferation. These two compounds may give new thought to the targeted therapy for patients with CCRCC.

12.
Health Educ Behav ; : 10901981211046533, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34628967

RESUMO

Most actions targeting children's health behaviors have limited involvement of children in the development, potentially contributing to disappointing effectiveness. Therefore, in the 3-year "Kids in Action" study, 9- to 12-year-old children from a lower-socioeconomic neighborhood were involved as coresearchers in the development, implementation, and evaluation of actions targeting health behaviors. The current study describes the controlled trial that evaluated the effects on children's energy balance-related behaviors, physical fitness, and self-rated health, as well as experienced challenges and recommendations for future evaluations. Primary school children from the three highest grades of four intervention and four control schools were eligible for participation. Outcome measures assessed at baseline, and at 1- and 2-year follow-up were as follows: motor fitness by the MOPER test (N = 656, N = 485, N = 608, respectively), physical activity and sedentary behavior by accelerometry (N = 223, N = 149, N = 164, respectively), and consumption of sugar sweetened beverages and snacks and self-rated health by a questionnaire (N = 322, N = 281, N = 275, respectively). Mixed-model analyses were performed adjusted for clustering within schools and relevant confounders. Significant beneficial intervention effects were found on self-reported consumption of energy/sports drinks at T2 versus T0, and on total time and ≥5-minute bouts of moderate-to-vigorous physical activity at T1 versus T0. Significant adverse effects were found on "speed and agility" and "coordination and upper-limb speed." No other significant effects were found. The inconsistent intervention effects may be explained by the dynamic cohort and suboptimal outcome measures. We advise future studies with a similar approach to apply alternative evaluation designs, such as the delayed baseline design.

13.
Polymers (Basel) ; 13(19)2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34641232

RESUMO

Different modification process routes are used to improve the modified cellulose nanocrystalline (MCNC) with higher fatty acid by esterification reaction and graft polymerization to obtain certain hydrophobic properties. Two preparation methods, product structure and surface activity, are compared and explored. Experimental results show that the modified product is still at the nanometer level and basically retains the crystal structure of the raw cellulose nanocrystalline (CNC). The energy consumption of the two preparation methods is low; however, the esterification method with co-reactant requires short reaction time, and the degree of substitution of the product is high. The modified product prepared by grafting polymerization method has a high HLB value and amphiphilicity, which can effectively reduce the surface tension of water. Therefore, it can be used as a green and environmentally friendly surface-active substance.

14.
Front Pharmacol ; 12: 711303, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34690756

RESUMO

Zhi-Zi-Hou-Po Decoction (ZZHPD) is a well-known traditional Chinese medicine (TCM) that has been widely used in depression. However, the antidepressant mechanism of ZZHPD has not yet been fully elucidated. The purpose of this study was to explore the pharmacological mechanisms of ZZHPD acting on depression by combining ultra flow liquid chromatography with quadrupole time-of-flight mass spectrometry (UFLC-Q-TOF/MS) and network pharmacology strategy. The chemical components of ZZHPD were identified using UFLC-Q-TOF/MS, while the potential drug targets and depression-related targets were collected from databases on the basis of the identified compounds of ZZHPD. Protein-protein interaction (PPI) network, gene ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were used to unravel potential antidepressant mechanisms. The predicted antidepressant targets from the pharmacology-based analysis were further verified in vivo. As a result, a total of 31 chemical compounds were identified by UFLC-Q-TOF/MS; 514 promising drug targets were mined by using the Swiss Target Prediction; and 527 depression-related target genes were pinpointed by the GeneCards and OMIM databases. STRING database and Cytoscape's topological analysis revealed 80 potential targets related to the antidepressant mechanism of ZZHPD. The KEGG pathway analysis revealed that the antidepressant targets of ZZHPD were mainly involved in dopaminergic synapse, serotonin synapse, cAMP, and mTOR signaling pathways. Furthermore, based on the animal model of depression induced by chronic corticosterone, the regulatory effects of ZZHPD on the expression of MAOA, MAOB, DRD2, CREBBP, AKT1, MAPK1, HTR1A, and GRIN2B mRNA levels as well as the cAMP signaling pathway and monoaminergic metabolism were experimentally verified in rats. Our study revealed that ZZHPD is expounded to target various genes and pathways to perform its antidepressant effect.

15.
Front Pharmacol ; 12: 748501, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34690779

RESUMO

The present study determines the potential antioxidants in Moutan Cortex (MC) and predicts its targets of anti-oxidative activities. The quantitative analysis and the free radical scavenging assays were conducted to detect the main components in MC and assess its anti-oxidant activities. The grey relational analysis and the network pharmacology approach were employed to predict its key components and targets of anti-oxidant activities. Six main constitutes in MCs were quantified by high performance liquid chromatography (HPLC) and its anti-oxidant activities were evaluated by DPPH and ABTS free radical scavenging methods. Then grey relational analysis was employed to predict the key components acting on anti-oxidative activity based on the chem-bio results. The predicted components and its mechanisms on anti-oxidation were uncovered by network pharmacology approach and cell test, respectively. The content of paeonol and paeoniflorin accounts for more than 80% the whole content of detected components. However, the two main ingredients showed a great variety among MCs. The antioxidant capacities of MCs also showed a great discrepancy based on DPPH and ABTS methods. The key components acting on anti-oxidation were identified to be paeonol, gallic acid and benzoylpaeoniflorin, and their potential therapeutic targets were predicted and verified, respectively. The present results reveal that MC has a significant antioxidant activity and the compounds of paeonol, gallic acid and benzoylpaeoniflorin could be considered as the promising antioxidant candidates with the property of suppressing oxidative stress and apoptosis.

16.
J Hepatocell Carcinoma ; 8: 1253-1267, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34708007

RESUMO

Background and Aims: Although antiviral treatment has been shown to reduce mortality in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients with high HBV-DNA levels, it is still unclear whether it is useful in reducing mortality in patients with low HBV-DNA levels. Methods: A retrospective analysis of 756 HBV-associated HCC patients at the Beijing Ditan Hospital with HBV-DNA levels < 500 IU/mL was conducted between January 2008 and June 2017. Patients were divided into antiviral and non-antiviral groups based on whether they received nucleos(t)ide analogue (NA) treatment when they were diagnosed with HCC in our hospital for the first time. We used 1:4 frequency matching by age, gender, tumor size, Barcelona Clinic Liver Cancer (BCLC) staging, anti-tumor therapy, cirrhosis, diabetes, and hyperlipoidemia to compare the antiviral (n = 366) and non-antiviral (n = 100) groups. A Cox multivariate regression analysis was employed to evaluate the effects of NA therapy on the hazard ratio (HR), and the Kaplan-Meier survival curve was used to determine the mortality risk in patients with HCC. A Log rank test was performed to analyze the effects of NA therapy on the survival rate of patients with HCC. Results: After propensity score matching, the 1-, 3-, and 5-year overall survival (OS) rates for the antiviral and non-antiviral groups were 82.5%, 68.6%, and 52.2%, and 61.0%, 51.0%, and 38.0%, respectively. The l-year progression-free survival (PFS) rates for the two groups were 68.0% and 47.0%, respectively. The OS of the antiviral group was significantly higher than that of the control group (P < 0.001, P = 0.001, and P = 0.013, respectively). The 1-year PFS for the antiviral group was also significantly better than that for the non-antiviral groups (P = 0.005). After adjusting for confounding prognostic factors in the Cox model, the HR of 5-year death after antiviral treatment was 0.721 (95% confidence interval [CI], 0.530-0.980, P = 0.037). Antiviral therapy is an independent protective factor for 5-year mortality in patients with HCC and low-level viremia. Conclusion: Antiviral therapy significantly reduced mortality in HCC patients with low HBV-DNA levels.

17.
Int J Mol Sci ; 22(20)2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34681660

RESUMO

Psoriasis (Pso) is a chronic inflammatory skin disease, and up to 30% of Pso patients develop psoriatic arthritis (PsA), which can lead to irreversible joint damage. Early detection of PsA in Pso patients is crucial for timely treatment but difficult for dermatologists to implement. We, therefore, aimed to find disease-specific immune profiles, discriminating Pso from PsA patients, possibly facilitating the correct identification of Pso patients in need of referral to a rheumatology clinic. The phenotypes of peripheral blood immune cells of consecutive Pso and PsA patients were analyzed, and disease-specific immune profiles were identified via a machine learning approach. This approach resulted in a random forest classification model capable of distinguishing PsA from Pso (mean AUC = 0.95). Key PsA-classifying cell subsets selected included increased proportions of differentiated CD4+CD196+CD183-CD194+ and CD4+CD196-CD183-CD194+ T-cells and reduced proportions of CD196+ and CD197+ monocytes, memory CD4+ and CD8+ T-cell subsets and CD4+ regulatory T-cells. Within PsA, joint scores showed an association with memory CD8+CD45RA-CD197- effector T-cells and CD197+ monocytes. To conclude, through the integration of in-depth flow cytometry and machine learning, we identified an immune cell profile discriminating PsA from Pso. This immune profile may aid in timely diagnosing PsA in Pso.

18.
Aging (Albany NY) ; 13(20): 23702-23725, 2021 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-34686627

RESUMO

OBJECT: Find potential therapeutic targets of triple-negative breast cancer (TNBC) patients by bioinformatics. Screen ideal natural ligand that can bind with the potential target and inhibit it by using molecular biology. METHODS: Bioinformatics and molecular biology were combined to analyze potential therapeutic targets. Differential expression analysis identified the differentially expressed genes (DEGs) between TNBC tissues and non-TNBC tissues. The functional enrichment analyses of DEGs shown the important gene ontology (GO) terms and pathways of TNBC. Protein-protein interaction (PPI) network construction screened 20 hub genes, while Kaplan website was used to analyze the relationship between the survival curve and expression of hub genes. Then Discovery Studio 4.5 screened ideal natural inhibitors of the potential therapeutic target by LibDock, ADME, toxicity prediction, CDOCKER and molecular dynamic simulation. RESULTS: 1,212 and 353 DEGs were respectively found between TNBC tissues and non-TNBC tissues, including 88 up-regulated and 141 down-regulated DEGs in both databases. 20 hub genes were screened, and the higher expression of CDC20 was associated with a poor prognosis. Therefore, we chose CDC20 as the potential therapeutic target. 7,416 natural ligands were conducted to bind firmly with CDC20, and among these ligands, ZINC000004098930 was regarded as the potential ideal ligand, owing to its non-hepatotoxicity, more solubility level and less carcinogenicity than the reference drug, apcin. The ZINC000004098930-CDC20 could exist stably in natural environment. CONCLUSION: 20 genes were regarded as hub genes of TNBC and most of them were relevant to the survival curve of breast cancer patients, especially CDC20. ZINC000004098930 was chosen as the ideal natural ligand that can targeted and inhibited CDC20, which may give great contribution to TNBC targeted treatment.

20.
Artigo em Inglês | MEDLINE | ID: mdl-34652999

RESUMO

Ultrasound is capable of non-invasive transcranial focusing and activating the targeted neurons in brain regions, receiving increasing attention. Ion channel, acting as a nano-ionic switch, enables to modulate the ion flow across cellular membranes and it is of importance to control the firing frequency of a neuron. In this letter, we demonstrate the behavioral response of the Caenorhabditis elegans (C. elegans) in response to ultrasound stimulation is mediated by the activation of mechanical sensitive MEC-4 and MEC-6 ion channels. By specific mutation of MEC-4 and MEC-6 ion channel, mutant worms show a significant decrease in the percentage of reversal behavior (30 ± 10.5% and 10 ± 6.9%, respectively), compared with wild type (85 ± 8.2%). Furthermore, ALM and PLM neurons expressing MEC-4 and MEC-6 ion channels could be evoked directly by ultrasound stimulation, indicating MEC-4 and MEC-6 may pave a new way for sonogenetics.

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