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2.
Artigo em Inglês | MEDLINE | ID: mdl-35029675

RESUMO

BACKGROUND: Current evidence on the association between Mediterranean diet (MeDi) intake and activities of daily living (ADL) is limited and inconsistent in older adults. METHODS: This study included 1696 participants aged ≥ 65 years in the Washington Heights-Inwood Community Aging Project (WHICAP) study. The MeDi score was calculated based on data collected from the Willett's semi-quantitative food frequency questionnaire. The multivariable-adjusted Cox regression model was applied to examine the association of MeDi score with risks of disability in basic (BADL) and instrumental ADL (IADL), as well as the overall ADL (B-IADL). RESULTS: 832 participants with incident ADL disability were identified over a median follow-up of 5.39 years. The continuous MeDi score was significantly associated with decreased risk of disability in B-IADL (hazard ratio [HR] = 0.95, 95% confidence interval [CI] = 0.91 to 0.99, p = 0.018) in a model adjusted for age, sex, race/ethnicity, educational level, and dietary calories intake but was no longer significant after additionally adjusted for multiple comorbidities and physical activities (0.97 [0.93, 1.01], p = 0.121). The continuous MeDi score was significantly associated with decreased risk of disability in B-IADL (0.92 [0.85, 1.00], p = 0.043) and BADL (0.90 [0.82, 0.99], p = 0.030) in non-Hispanic Whites, but not in non-Hispanic Blacks and Hispanics (p > 0.05 for all). CONCLUSIONS: Higher MeDi score was associated with decreased risk of ADL disability, particularly in non-Hispanic Whites.

3.
Trials ; 23(1): 11, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983602

RESUMO

INTRODUCTION: Insomnia disorder (ID) is characterized by dissatisfaction with the quantity or quality of sleep and is often accompanied by negative emotions such as anxiety and depression. Patients with insomnia become trapped in a vicious circle of bad moods and poor sleep. Resting-state functional magnetic resonance imaging (r-fMRI) studies have shown abnormalities in emotion-related brain networks in patients with ID. And it has been proven that reducing negative emotions improves sleep quality. As a traditional alternative therapy, acupuncture has been demonstrated to be effective not only in improving sleep quality but also in stabilizing emotions; however, the mode of action needs to be further explored. Therefore, a clinical trial was designed to explore the effect of acupuncture in improving sleep and mood and to intuitively investigate the regulation of the emotional network using fMRI. METHODS AND ANALYSIS: A total of 60 participants with ID will be randomly allocated to a spirit-regulating group or a control group using non-effective acupoints acupuncture at a ratio of 1:1. All participants will receive 3 acupuncture treatment sessions per week for 4 weeks. In addition, 30 healthy individuals will be included in the healthy group. The primary outcome is the Pittsburgh Sleep Quality Index (PSQI). Secondary outcomes are the Hamilton Anxiety Scale (HAMA), the Hamilton Depression Scale (HAMD), the Hyperarousal Scale (HAS), and the Fatigue Scale-14 (FS-14), r-fMRI data, sleep diary, and actigraphy. The data will be collected prior to treatment, following treatment, and during the 12-week follow-up period; a sleep diary will be kept during the entire process. ETHICS AND DISSEMINATION: This protocol has been approved by the Research Ethical Committee of Beijing Hospital of Traditional Chinese Medicine (Bejing TCM Hospital). The results will be published in peer-reviewed journals or presented at academic conferences. TRIAL REGISTRATION: Chinese Clinical Trials Register ChiCTR1800015282 . Protocol version: Version 1.0. Date: Dec.2020.


Assuntos
Terapia por Acupuntura , Distúrbios do Início e da Manutenção do Sono , Adulto , Emoções , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sono , Distúrbios do Início e da Manutenção do Sono/diagnóstico , Distúrbios do Início e da Manutenção do Sono/terapia , Resultado do Tratamento
4.
Mol Biol Rep ; 2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-34997871

RESUMO

BACKGROUND: Melatonin can regulate apoptosis and autophagy of mouse Leydig cells, but its specific mechanism is still unclear. METHODS: In this study, we used the TM3 cell line as the research object, and used H2O2 to induce autophagy. After adding 10 ng/ml melatonin, we used qRT-PCR and western-blot to detect autophagy-related gene and protein expression, and flow cytometry to detect cellular ROS level. RESULTS: The results showed that melatonin can significantly inhibit the occurrence of autophagy, accompanied by a significant decrease in the expression of Becn1, LC3, and FOXO1 (P < 0.05), a significant increase in the expression of p62 and pAKT (P < 0.05), and a significant decrease in ROS level (P < 0.05). After added the inhibitor of AKT perifosine, the effect of melatonin on inhibiting autophagy was reversed. On this basis, we used small RNA interference technology to knock down the expression of FOXO1, and found that there was no significant change of the expression of genes and proteins related to autophagy and ROS level. CONCLUSIONS: In summary, melatonin can inhibit H2O2-induced autophagy in TM3 cells through the AKT/FOXO1 pathway.

6.
J Cell Mol Med ; 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35023280

RESUMO

Ferroptosis is a regulated cell death nexus linking metabolism, redox biology and diseases including cancer. The aim of the present study was to identify a ferroptosis-related gene prognostic signature for stomach adenocarcinoma (STAD) by systematic analysis of transcriptional profiles from The Cancer Genome Atlas (TCGA), GEO and a clinical cohort from our centre. We developed a predictive model based on three ferroptosis-related genes (CHAC1, NOX4 and HIF1A), gene expression data and corresponding clinical outcomes were obtained from the TCGA database, and the reliability of this model was verified with GSE15459 and 51 queues in our centre. ROC curve showed better predictive ability using the risk score. Immune cell enrichment analysis demonstrated that the types of immune cells and their expression levels in the high-risk group were significantly different from those in the low-risk group. The experimental results confirmed that NOX4 was upregulated and CHAC1 was downregulated in the STAD tissues compared with the normal stomach mucosal tissues (p < 0.05). In sum, the ferroptosis-related gene signature can accurately predict the outcomes of patients with STAD, providing valuable insights for personalized treatment. As the signature also has relevance to the immune characteristics, it may help improve the efficacy of personalized immunotherapy.

7.
Environ Pollut ; : 118816, 2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-35016984

RESUMO

As primary anthropogenic emission source of toxic pollutants such as heavy metals and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), municipal solid waste (MSW) incineration has caused worldwide concern. However, a comprehensive analysis of the pollution characteristics and health risks of PCDD/Fs and heavy metals in soils around MSW incineration plants is lacking. In this study, 17 PCDD/Fs and 11 heavy metals in soil samples collected near MSW incineration plants in Sichuan province were investigated to evaluate their pollution characteristics and potential health risk. Sichuan was selected as the study area because the MSW incineration amount in this province ranks first among all inland provinces in China. The PCDD/Fs concentrations ranged from 0.30 to 7.50 ng I-TEQ/kg, which were significantly below risk screening and intervention thresholds. Regarding heavy metals, principal component analysis suggested that Hg, Pb and Zn were the primary metals emitted from the MSW incineration plants. Cluster analysis of PCDD/Fs and heavy metals showed that of PCDD/Fs homologs and heavy metals (e.g., Hg, Pb, Zn and Cd) were clustered into one group, indicating the coexistence and coaccumulation of heavy metals (especially Hg, Pb, Zn, and Cd) and PCDD/Fs in soil. These heavy metals are thus candidate tracers for PCDD/Fs in soil near MSW incineration plants. A health risk analysis found that the carcinogenic and non-carcinogenic risks of PCDD/Fs and heavy metals (except for Ni) in the soil samples were all within acceptable levels. This study provides new insights into correlations and health risks of PCDD/Fs and heavy metals in surface soil near MSW incineration plants. The findings have implications for future studies of environmental and human health risk analysis related to waste incineration.

9.
Aging Cell ; : e13551, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35032339

RESUMO

Senescence of bone marrow mesenchymal stem cells (BMSCs) impairs stemness and osteogenic differentiation, but the key regulators for senescence and the related osteogenesis are not well defined. Herein, we screened the gene expression profiles of human BMSCs from young and old donors and identified that elevation of the nucleosome assembly protein 1-like 2 (NAP1L2) expression was correlated with BMSC senescence and impaired osteogenesis. Elevated NAP1L2 expression was observed in replicative cell senescence and induced cell senescence in vitro, and in age-related senescent human and mouse BMSCs in vivo, concomitant with significantly augmented chromatin accessibility detected by ATAC-seq. Loss- and gain-of-functions of NAP1L2 affected activation of NF-κB pathway, status of histone 3 lysine 14 acetylation (H3K14ac), and chromatin accessibility on osteogenic genes in BMSCs. Mechanistic studies revealed that NAP1L2, a histone chaperone, recruited SIRT1 to deacetylate H3K14ac on promoters of osteogenic genes such as Runx2, Sp7, and Bglap and suppressed the osteogenic differentiation of BMSCs. Importantly, molecular docking analysis showed a possible bond between NAP1L2 and an anti-aging reagent, the nicotinamide mononucleotide (NMN), and indeed, administration of NMN alleviated senescent phenotypes of BMSCs. In vivo and clinical evidence from aging mice and patients with senile osteoporosis also confirmed that elevation of NAP1L2 expression was associated with suppressed osteoblastogenesis. Taken together, our findings suggest that NAP1L2 is a regulator of both BMSC cell senescence and osteogenic differentiation, and provide a new theoretical basis for aging-related disease.

10.
J Sci Food Agric ; 102(1): 175-184, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34061382

RESUMO

BACKGROUND: To improve the aroma of kiwi wine through the utilization of Wickerhamomyces anomalus, kiwi juice was fermented using a selected W. anomalus strain in pure culture and mixed fermentations with Saccharomyces cerevisiae, which was inoculated simultaneously and sequentially. The physicochemical indices, volatile compounds and aroma properties of the kiwi wines were assessed. RESULTS: The study suggested that the ethanol, color indices and organic acids of the wines were closely related to the method of inoculation. Compared with the pure S. cerevisiae fermentation, the mixed fermentations produced more varieties and concentrations of volatiles. The sequential fermentations increased the concentrations of esters and terpenes, improving the flower and sweet fruit notes of the wines. The simultaneous inoculation enhanced the contents of esters and aldehydes, intensifying the flower, sweet and sour fruit of the wines. Partial least-squares regression analysis showed that esters and terpenes contributed greatly to the flower and sweet fruit aroma, whereas aldehydes were the major contributors to the sour note. CONCLUSION: Based on our results, the mixed fermentations not only enriched the types and concentrations of volatiles, but also had better sensory properties. © 2021 Society of Chemical Industry.


Assuntos
Actinidia/microbiologia , Saccharomyces cerevisiae/metabolismo , Saccharomycetales/metabolismo , Compostos Orgânicos Voláteis/química , Compostos Orgânicos Voláteis/metabolismo , Vinho/análise , Actinidia/metabolismo , Etanol/análise , Etanol/metabolismo , Fermentação , Frutas/metabolismo , Frutas/microbiologia , Humanos , Odorantes/análise , Paladar , Vinho/microbiologia
11.
Toxicol Appl Pharmacol ; 435: 115850, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34968637

RESUMO

Cigarettes consumption is continued to be popular. We found that cigarette smoke (CS) exposure promoted prostatic fibrosis. In this study, human prostate epithelial RWPE-1 cells were co-cultured with exosomes derived from CS exposed-WPMY-1 cells (CS-WPMY-1-exo). The collagen deposition, primary ciliogenesis, epithelial-mesenchymal transition (EMT) and transforming growth factor (TGF)-ß1 level of RWPE-1 were evaluated. The circRNAs profiles of WPMY-1-exo were explored by high-throughput RNA sequencing. It was found that CS-WPMY-1-exo significantly promoted RWPE-1 collagen deposition, EMT and primary ciliogenesis. There were 17 differentially expressed (DE) circRNAs (including circ_0001359) between CS-WPMY-1-exo and the negative control. Functional enrichment analyses showed that the DE circRNAs played important roles in ciliary basal body, spindle microtubule and TGF-ß signaling pathway. Circ_0001359 siRNA attenuated CS-WPMY-1 induced RWPE-1 cells collagen deposition, EMT and primary ciliogenesis, as well as inhibited the level of TGF-ß1. The whole results showed that circ_0001359 derived from CS-WPMY-1-exo contributed to prostatic fibrosis via stimulating epithelial cells phenotypes changes and collagen deposition.

13.
Pathog Dis ; 79(9)2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34928326

RESUMO

Hand foot and mouth disease (HFMD) is an infectious disease mainly caused by Enterovirus 71 (EV 71). However, the effective treatment is limited currently. The aim of this study was to investigate the activity of the vaccine including the EV71 polypeptides mixed with a novel adjuvant containing CpG oligodeoxynucleotides (CpG ODNs). After collecting mouse sera, we determined the antibody concentration in serum by enzyme-linked immunosorbent assays (ELISA). Then, CD19+CD27+ B cells in the spleen were analysed by flow cytometry. The assay revealed that a substantial increase in antibody titers was achieved. This indicates a high level of immunogenicity for peptide vaccine and the good stability of adjuvant, also suggests that the combination of vaccine and adjuvant can stimulate the production of high-level antibodies and CD19+CD27+ B lymphocytes in mice. Furthermore, the antibody could effectively identify EV71 inactivated virus. The results demonstrated that the autonomous construction of EV71 polypeptide vaccine had a good immunogenicity. Moreover, the peptide vaccine injection with a novel adjuvant, which is easy to prepare, could cause a high antibody level of EV71 and shown a good application prospect.

14.
Proc Inst Mech Eng H ; : 9544119211060100, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34847817

RESUMO

With the evolving demands of surgical intervention, there is a strong need for smaller and functionally augmented instruments to improve surgical outcomes, operational convenience, and diagnostic safety. Owing to the narrow and complicated anatomy, the probe head of the medical instrument is required to possess both good maneuverability and compact size. In addition, the development of medical instrument is moving toward patient-specialized, of which the articulation positions can be customized to reach the target position. To fulfill these requirements, this study presents the design of a smart handheld device which equips with a low cost, easy control, disposable flexible wrist, and an electrical bioimpedance sensor for medical diagnosis. Prototype of the device is made and tested. The experimental results demonstrate that the proposed device can provide accurate manipulation and effective tissue detection, showing a great potential in various medical applications.

15.
Reprod Biomed Online ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34848150

RESUMO

RESEARCH QUESTION: Which of the two mainstream endometrial preparation regimens, assisted natural cycle (NC) or hormone replacement treatment cycle (HRT), help frozen-thawed embryo transfer (FET) cycles after preimplantation genetic testing (PGT) achieve better clinical outcomes? DESIGN: This retrospective analysis included 3400 vitrified-warmed single blastocyst transfer cycles after PGT from January 2011 to November 2020, and involved 2332 patients with regular menstrual cycles. The decision to proceed with an assisted NC (n = 827) or HRT (n = 2573) before FET was reached based on a combination of patient preference and physician guidance. Clinical pregnancy rate, live birth rate, early miscarriage rate and obstetric outcomes were compared. RESULTS: No significant difference was observed between the assisted NC and HRT groups in terms of clinical pregnancy rate (51.6% versus 50.7%, P = 0.634), live birth rate (44.0% versus 43.4%, P = 0.746) or early miscarriage rate (12.6% versus 12.0%, P = 0.707). Multivariate analysis indicated that the endometrial preparation protocol was not an independent factor for a clinical pregnancy or live birth. In the HRT group, the Caesarean section rate (64.7% versus 51.9%, P < 0.001) and pregnancy complication rate (20.2% versus 13.8%, P = 0.003) were significantly higher. The two groups were not statistically different with respect to gestational age, early preterm birth rate, fetal weight or fetal birth defect rate. CONCLUSIONS: For patients undergoing a PGT-FET cycle involving a single blastocyst transfer, using assisted NC and HRT for the endometrial preparation could lead to comparable rates of clinical pregnancy and live birth. Additionally, NC is safer than HRT in terms of avoiding pregnancy complications and adverse obstetric outcomes.

16.
Front Pharmacol ; 12: 754387, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34867366

RESUMO

Atherosclerotic cardiovascular disease is a common and severe complication of diabetes. There is a large need to identify the effective and safety strategies on diabetic cardiovascular disease (DCVD). 9-PAHSA is a novel endogenous fatty acid, and has been reported to reduce blood glucose levels and attenuate inflammation. We aim to evaluate the effects of 9-PAHSA on DCVD and investigate the possible mechanisms underlying it. Firstly, serum 9-PAHSA levels in human were detected by HPLC-MS/MS analysis. Then 9-PAHSA was synthesized and purified. The synthesized 9-PAHSA was gavaged to db/db mice with 50 mg/kg for 4 weeks. The carotid arterial plaque and cardiac structure was assessed by ultrasound. Cardiac autophagy was tested by western blot analysis, electron microscope and iTRAQ. The results showed that 9-PAHSA, in patients with type 2 diabetes mellitus (T2DM), was significantly lower than that in non-diabetic subjects. Administration of 9-PAHSA for 2 weeks reduced blood glucose levels. Ultrasound observed that continue administration of 9-PAHSA for 4 weeks ameliorated carotid vascular calcification, and attenuated myocardial hypertrophy and dysfunction in db/db mice. Electron microscopy showed continue 9-PAHSA treatment significantly increased autolysosomes, while dramatically decreased greases in the myocardial cells of the db/db mice. Moreover, iTRAQ analysis exhibited that continue 9-PAHSA treatment upregulated BAG3 and HSPB8. Furthermore, western blot analysis confirmed that 9-PAHSA down-regulated Akt/mTOR and activated PI3KIII/BECN1 complex in diabetic myocardium. Thus, 9-PAHSA benefits DCVD in diabetic mice by ameliorating carotid vascular calcification, promoting autophagic flux and reducing myocardial hypertrophy.

17.
Nano Lett ; 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34870433

RESUMO

As essential units in an artificial neural network (ANN), artificial synapses have to adapt to various environments. In particular, the development of synaptic transistors that can work above 125 °C is desirable. However, it is challenging due to the failure of materials or mechanisms at high temperatures. Here, we report a synaptic transistor working at hundreds of degrees Celsius. It employs monolayer MoS2 as the channel and Na+-diffused SiO2 as the ionic gate medium. A large on/off ratio of 106 can be achieved at 350 °C, 5 orders of magnitude higher than that of a normal MoS2 transistor in the same range of gate voltage. The short-term plasticity has a synaptic transistor function as an excellent low-pass dynamic filter. Long-term potentiation/depression and spike-timing-dependent plasticity are demonstrated at 150 °C. An ANN can be simulated, with the recognition accuracy reaching 90%. Our work provides promising strategies for high-temperature neuromorphic applications.

18.
Eur J Med Chem ; 228: 114022, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34871843

RESUMO

Tropomyosin receptor kinases A (TrkA) is a potential therapeutic target for the treatment of numerous tumor types and chronic pain. However, most of the reported TrkA inhibitors are ATP competitive pan-Trks inhibitors that lack subtype selectivity. A selective TrkA inhibitor may provide valuable therapeutic benefits. Here, we described the discovery of novel TrkA allosteric inhibitors by structure-based virtual screening. A promising hit (D5261, TrkA cell IC50 = 3.32 µM) was selected for further studies. The binding free energy between TrkA and D5261 was calculated. In addition, the preliminary structure-activity relationship (SAR) studies with D5261 were investigated. The results suggest that D5261 can be used as a starting point for development of TrkA allosteric inhibitors.

19.
BMC Pulm Med ; 21(1): 399, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34872558

RESUMO

BACKGROUND: Drug-resistant tuberculosis (DR-TB), obesity, and malnutrition are growing public health problems in the world. However, little has discussed the impact of different BMI status on the emergence of TB drug resistance. We aimed to explore the drug-resistant profiles of DR-TB and its clinical predictors among underweight, overweight or obesity population. METHODS: 8957 newly diagnosed TB cases with drug susceptibility results and BMI data in Shandong China, from 2004 to 2019 were enrolled. Multivariable and univariable logistic regression models were applied to investigate the impact of BMI on different drug-resistance. Clinical predicators and drug-resistant profiles of DR-TB among obesity, underweight, normal TB group were also described. RESULTS: Among 8957 TB cases, 6417 (71.64%) were normal weight, 2121 (23.68%) were underweight, 373 (4.16%) were overweight, and 46 (0.51%) were obese. The proportion of drug resistance and co-morbidity among normal weight, underweight, overweight, obese TB groups were 18.86%/18.25%/20.38%/23.91% (DR-TB), 11.19%/11.74%/9.65%/17.39% (mono-resistant tuberculosis, MR-TB), 3.41%/3.06%/5.36%/0.00% (multidrug resistant tuberculosis, MDR-TB), 4.21%/3.39%/5.36%/6.52% (polydrug resistant tuberculosis, PDR-TB), 10.57%/8.44%/19.57%/23.91% (co-morbidity), respectively. Compared with normal weight group, underweight were associated with lower risk of streptomycin-related resistance (OR 0.844, 95% CI 0.726-0.982), but contributed to a higher risk of MR-TB (isoniazid) (odds ratio (OR) 1.347, 95% CI 1.049-1.730; adjusted OR (aOR) 1.31, 95% CI 1.017-1.686), P < 0.05. In addition, overweight were positively associated with MDR-TB (OR 1.603, 95% CI 1.002-2.566; aOR 1.639, 95% CI 1.02-2.633), isoniazid + rifampicin + streptomycin resistance (OR 1.948, 95% confidence interval (CI): 1.061-3.577; aOR 2.113, 95% CI 1.141-3.912), Any isoniazid + streptomycin resistance (OR 1.472, 95% CI 1.013-2.14; aOR 1.483, 95% CI 1.017-2.164), P < 0.05. CONCLUSIONS: The higher risk of MDR-TB, isoniazid + rifampicin + streptomycin resistance, Any isoniazid + streptomycin resistance, and co-morbidity among overweight population implies that routine screening for drug sensitivity and more attention on co-morbidity among overweight TB cases may be necessary. In addition, underweight TB cases have a higher risk of isoniazid resistance. Our study suggests that an in-depth study of the interaction between host metabolic activity and infection of DR-TB may contribute more to novel treatment options or preventive measures, and accelerate the implementation of the STOP TB strategy.

20.
Environ Int ; 159: 107009, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34883459

RESUMO

Endocrine-disrupting chemicals (EDCs) can compete with endogenous hormones and bind to the orthosteric site of nuclear receptors (NRs), affecting normal endocrine system function and causing severe symptoms. Recently, a series of pharmaceuticals and personal care products (PPCPs) have been discovered to bind to the allosteric sites of NRs and induce similar effects. However, it remains unclear how diverse EDCs work in this new way. Therefore, we have systematically summarized the allosteric sites and underlying mechanisms based on existing studies, mainly regarding drugs belonging to the PPCP class. Advanced methods, classified as structural biology, biochemistry and computational simulation, together with their advantages and hurdles for allosteric site recognition and mechanism insight have also been described. Furthermore, we have highlighted two available strategies for virtual screening of numerous EDCs, relying on the structural features of allosteric sites and lead compounds, respectively. We aim to provide reliable theoretical and technical support for a broader view of various allosteric interactions between EDCs and NRs, and to drive high-throughput and accurate screening of potential EDCs with non-competitive effects.

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