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1.
Mol Cell Endocrinol ; 539: 111485, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34619292

RESUMO

Adipogenesis is regulated by a complicated network of transcription factors among which PPARγ and C/EBP family members are the major regulators. During adipogenesis, C/EBPß is induced early and then transactivates PPARγ and C/EBPα, which cooperatively induce genes whose expressions give rise to the mature adipocyte phenotype. Identifying the factors that influence the expression and activity of C/EBPß should provide additional insight into the mechanisms regulating adipogenesis. Here, we demonstrate that depletion of Ajuba in 3T3-L1 cells significantly decreases mRNA and protein levels of PPARγ and C/EBPα and impairs adipocyte differentiation, while overexpression increases expression of these genes and promotes adipocyte differentiation. Moreover, restoration of C/EBPα or PPARγ expression in Ajuba-deficient 3T3-L1 cells improves the impaired lipid accumulation. Mechanistically, Ajuba interacts with C/EBPß and recruits CBP to facilitate the binding of C/EBPß to the promoter of PPARγ and C/EBPα, resulting in increased H3 histone acetylation and target gene expression. Collectively, these data indicate that Ajuba functions as a co-activator of C/EBPß, and may be an important therapeutic target for combating obesity-related diseases.

2.
iScience ; 24(10): 103136, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34723160

RESUMO

The ever-growing installation of solar power systems imposes severe challenges on the operations of local and regional power grids due to the inherent intermittency and variability of ground-level solar irradiance. In recent decades, solar forecasting methodologies for intra-hour, intra-day and day-ahead energy markets have been extensively explored as cost-effective technologies to mitigate the negative effects on the power grids caused by solar power instability. In this work, the progress in intra-hour solar forecasting methodologies are comprehensively reviewed and concisely summarized. The theories behind the forecasting methodologies and how these theories are applied in various forecasting models are presented. The reviewed mathematical tools include regressive methods, stochastic learning methods, deep learning methods, and genetic algorithm. The reviewed forecasting methodologies include data-driven methods, local-sensing methods, hybrid forecasting methods, and application orientated methods that generate probabilistic forecasts and spatial forecasts. Furthermore, suggestions to accelerate the development of future intra-hour forecasting methods are provided.

3.
Psychogeriatrics ; 2021 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-34743400

RESUMO

BACKGROUND: Depression is common in patients with multimorbidity, but little is known about the relationship between depression and multimorbidity. The purpose of our research was to investigate multimorbidity patterns and their association with depression in a sample of older people covered by long-term care insurance in Shanghai, China. METHOD: This was a population-based cross-sectional study, with 1871 participants aged ≥60 years old who are covered by Shanghai long-term care insurance. Multimorbidity was defined as the presence of two or more chronic diseases at the same time. We collected information on chronic conditions using a self-reported medical history, and we used the 30-item Geriatric Depression Scale (GDS-30) to evaluate depressive symptoms. Patterns of multimorbidity were identified with exploratory factor analysis, using oblimin rotation. Logistic regression was used to estimate the relationship between multimorbidity patterns and depressive symptoms. RESULTS: Among the participants, the prevalence of multimorbidity was 64.7%, and the prevalence of depression was 64.6%. Hypertension, cardiovascular disease, cerebrovascular disease (CVD), and cataracts showed strong associations with depression when co-occurring with other conditions. Three patterns of multimorbidity were identified: a musculoskeletal pattern, cardiometabolic pattern, and degenerative disease pattern. Among these, the cardiometabolic (adjusted odds ratio (AOR) 1.223; 95% confidence interval (CI) 1.102, 1.357) and degenerative disease (AOR 1.185; 95% CI 1.071, 1.311) patterns were associated with a higher risk of depressive symptoms. CONCLUSION: Two of three multimorbidity patterns were found to be associated with depression. Physical and psychological dimensions require greater attention in the care of older adults who are covered by long-term care insurance.

4.
Environ Chem Lett ; : 1-11, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34744548

RESUMO

Despite large decreases of emissions of air pollution during the coronavirus disease 2019 (COVID-19) lockdown in 2020, an unexpected regional severe haze has still occurred over the North China Plain. To clarify the origin of this pollution, we studied air concentrations of fine particulate matter (PM2.5), NO2, O3, PM10, SO2, and CO in Beijing, Hengshui and Baoding during the lockdown period from January 24 to 29, 2020. Variations of PM2.5 composition in inorganic ions, elemental carbon and organic matter were also investigated. The HYSPLIT model was used to calculate backward trajectories and concentration weighted trajectories. Results of the cluster trajectory analysis and model simulations show that the severe haze was caused mainly by the emissions of northeastern non-stopping industries located in Inner Mongolia, Liaoning, Hebei, and Tianjin. In Beijing, Hengshui and Baoding, the mixing layer heights were about 30% lower and the maximum relative humidity was 83% higher than the annual averages, and the average wind speeds were lower than 1.5 m s-1. The concentrations of NO3 -, SO4 2-, NH4 +, organics and K+ were the main components of PM2.5 in Beijing and Hengshui, while organics, K+, NO3 -, SO4 2-, and NH4 + were the main components of PM2.5 in Baoding. Contrary to previous reports suggesting a southerly transport of air pollution, we found that northeast transport caused the haze formation. Supplementary Information: The online version contains supplementary material available at 10.1007/s10311-021-01314-8.

5.
Front Pharmacol ; 12: 744494, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603057

RESUMO

Acinetobacter baumannii is an opportunistic pathogen predominantly associated with nosocomial infections. With emerging resistance against polymyxins, synergistic combinations of drugs are being investigated as a new therapeutic approach. Capsaicin is a common constituent of the human diet and is widely used in traditional alternative medicines. The present study evaluated the antibacterial activities of capsaicin in combination with colistin against three unrelated colistin-resistant Acinetobacter baumannii strains in vitro and in vivo, and then further studied their synergistic mechanisms. Using the checkerboard technique and time-kill assays, capsaicin and colistin showed a synergistic effect on colistin-resistant A. baumannii. A mouse bacteremia model confirmed the in vivo effects of capsaicin and colistin. Mechanistic studies shown that capsaicin can inhibit the biofilm formation of both colistin-resistant and non-resistant A. baumannii. In addition, capsaicin decreased the production of intracellular ATP and disrupted the outer membrane of A. baumannii. In summary, the synergy between these drugs may enable a lower concentration of colistin to be used to treat A. baumannii infection, thereby reducing the dose-dependent side effects. Hence, capsaicin-colistin combination therapy may offer a new treatment option for the control of A. baumannii infection.

6.
J Pathol Clin Res ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34618413

RESUMO

The tumor microenvironment (TME), including immune cells, cancer-associated fibroblasts, endothelial cells, adjacent normal cells, and others, plays a crucial role in influencing tumor behavior and progression. Here, we characterized the TME in 83 primary renal tumors and matched metastatic or recurrence tissue samples (n = 15) from papillary renal cell carcinoma (pRCC) types 1 (n = 20) and 2 (n = 49), collecting duct carcinomas (CDC; n = 14), and high-grade urothelial carcinomas (HGUC; n = 5). We investigated 10 different markers of immune infiltration, vasculature, cell proliferation, and epithelial-to-mesenchymal transition by using machine learning image analysis in conjunction with immunohistochemistry. Marker expression was compared by Mann-Whitney and Kruskal-Wallis tests and correlations across markers using Spearman's rank correlation coefficient. Multivariable Poisson regression analysis was used to compare marker expression between histological types, while accounting for variation in tissue size. Several immune markers showed different rates of expression across histological types of renal carcinoma. Using pRCC1 as reference, the incidence rate ratio (IRR) of CD3+ T cells (IRR [95% confidence interval, CI] = 2.48 [1.53-4.01]) and CD20+ B cells (IRR [95% CI] = 4.38 [1.22-5.58]) was statistically significantly higher in CDC. In contrast, CD68+ macrophages predominated in pRCC1 (IRR [95% CI] = 2.35 [1.42-3.9]). Spatial analysis revealed CD3+ T-cell and CD20+ B-cell expressions in CDC to be higher at the proximal (p < 0.0001) and distal (p < 0.0001) tumor periphery than within the central tumor core. In contrast, expression of CD68+ macrophages in pRCC2 was higher in the tumor center compared to the proximal (p = 0.0451) tumor periphery and pRCC1 showed a distance-dependent reduction, from the central tumor, in CD68+ macrophages with the lowest expression of CD68 marker at the distal tumor periphery (p = 0.004). This study provides novel insights into the TME of rare kidney cancer types, which are often understudied. Our findings of differences in marker expression and localization by histological subtype could have implications for tumor progression and response to immunotherapies or other targeted therapies.

7.
Front Oncol ; 11: 695001, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616672

RESUMO

Hepatocellular carcinoma is a common malignant tumor with poor prognosis, poor treatment effect, and lack of effective biomarkers. In this study, bioinformatics analysis of immune-related genes of hepatocellular carcinoma was used to construct a multi-gene combined marker that can predict the prognosis of patients. The RNA expression data of hepatocellular carcinoma were downloaded from The Cancer Genome Atlas (TCGA) database, and immune-related genes were obtained from the IMMPORT database. Differential analysis was performed by Wilcox test to obtain differentially expressed genes. Univariate Cox regression analysis, lasso regression analysis and multivariate Cox regression analysis were performed to establish a prognostic model of immune genes, a total of 5 genes (HDAC1, BIRC5, SPP1, STC2, NR6A1) were identified to construct the models. The expression levels of 5 genes in HCC tissues were significantly different from those in paracancerous tissues. The Kaplan-Meier survival curve showed that the risk score calculated according to the prognostic model was significantly related to the overall survival (OS) of HCC. The receiver operating characteristic (ROC) curve confirmed that the prognostic model had high accuracy. Independent prognostic analysis was performed to prove that the risk value can be used as an independent prognostic factor. Then, the gene expression data of hepatocellular carcinoma in the ICGC database was used as a validation data set for the verification of the above steps. In addition, we used the CIBERSORT software and TIMER database to conduct immune infiltration research, and the results showed that the five genes of the model and the risk score have a certain correlation with the content of immune cells. Moreover, through Gene Set Enrichment Analysis (GSEA) and the construction of protein interaction networks, we found that the p53-mediated signal transduction pathway is a potentially important signal pathway for hepatocellular carcinoma and is positively regulated by certain genes in the prognostic model. In conclusion, this study provides potential targets for predicting the prognosis and treatment of hepatocellular carcinoma patients, and also provides new ideas about the correlation between immune genes and potential pathways of hepatocellular carcinoma.

8.
Biochem Biophys Rep ; 28: 101144, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34622038

RESUMO

Temozolomide (TMZ) is a widely used chemotherapeutic agent for malignant glioma. ß-Elemene has been reported to have the ability of passing through the blood-brain barrier and reverse multidrug resistance. In the present study, transport of drugs through the in vitro blood-brain barrier (BBB) model also suggested that ß-elemene can assist in TMZ transport to the brain. Plasma and brain pharmacokinetics demonstrated that when ß-elemene is used in combination with TMZ, the metabolic rate of TMZ in plasma is slowed, and mean residence time (MRT) in brain is prolonged. The brain tissue distribution at 1 h indicated that the combination of TMZ and ß-elemene promotes the distribution of ß-elemene in the brain but slightly reduces the distribution of TMZ in the brain. Furthermore the antitumor effect and toxicity in vivo were also investigated. The combination of ß-elemene and TMZ was well tolerated and significantly inhibited tumor growth in glioma xenografts. In summary, the present study indicates a synergistic antitumor effect of ß-elemene and TMZ in glioma.

9.
Oncol Rep ; 46(6)2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34617573

RESUMO

The secreted frizzled related proteins (SFRPs) are extracellular inhibitors of WNT pathway signaling. Methyl­CpG binding domain protein 2 (MBD2) and enhancer of zeste homolog 2 (EZH2) are core members of the methylated DNA binding domain (MBD) and polycomb group (PcG) protein families for epigenetic regulation, respectively. This study aimed to ascertain the potential role of MBD2 and EZH2 proteins in colorectal cancer (CRC) and its effects on the expression of SFRP. Bioinformatics, real­time quantitative polymerase chain reaction (qPCR) and western blot analysis were used to detect the expression of MBD2, EZH2, and SFRP in CRC cell lines and tissues. The functions of MBD2 and EZH2 in regards to cell proliferation, cell cycle distribution, apoptosis and invasion were examined in CRC cell lines. Methylation­specific PCR (MSP) was used to detect the methylation status of the SFRP promoter. The results revealed that the mRNA expression levels of SFRP were significantly decreased in CRC tissues and cell lines compared to these levels in the adjacent tissues and NCM460, respectively. However, the mRNA levels of EZH2 and MBD2 genes were highly expressed in CRC cell lines. We found that reducing MBD2 and EZH2 expression together remarkably inhibited and decreased the proliferation, migration and invasion abilities of the CRC cell lines compared to reducing one of each. Flow cytometric analysis showed that knockdown of MBD2 and EZH2 together in CRC affected cell apoptosis and the cell cycle progression more effectively than knockdown of one of each. The mRNA expression of SFRP1 was reactivated by silencing of MBD2 but not EZH2 in SW480 and HCT116 cells. SFRP4 and SFRP5 mRNA expression was reactivated by silencing of EZH2 but not MBD2 only in SW480 cells. However, depletion of both MBD2 and EZH2 restored SFRP1, SFRP2, SFRP4, and SFRP5 mRNA expression more effectively in CRC cells. Interestingly, there was no significant change in the methylation status of SFRP1, SFRP2, SFRP4, and SFRP5 gene promoter between before and after interference with MBD2, EZH2, and both. In conclusion, our results suggest that silencing of MBD2 and EZH2 simultaneously was able to rescue the expression of SFRP and inhibit the proliferation of CRC cells more effectively. However, the underlying regulatory mechanism system of MBD2 and EZH2 for SFRP in CRC requires further research.

10.
Front Hum Neurosci ; 15: 727139, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34690720

RESUMO

Sleep staging is one of the important methods to diagnosis and treatment of sleep diseases. However, it is laborious and time-consuming, therefore, computer assisted sleep staging is necessary. Most of the existing sleep staging researches using hand-engineered features rely on prior knowledges of sleep analysis, and usually single channel electroencephalogram (EEG) is used for sleep staging task. Prior knowledge is not always available, and single channel EEG signal cannot fully represent the patient's sleeping physiological states. To tackle the above two problems, we propose an automatic sleep staging network model based on data adaptation and multimodal feature fusion using EEG and electrooculogram (EOG) signals. 3D-CNN is used to extract the time-frequency features of EEG at different time scales, and LSTM is used to learn the frequency evolution of EOG. The nonlinear relationship between the High-layer features of EEG and EOG is fitted by deep probabilistic network. Experiments on SLEEP-EDF and a private dataset show that the proposed model achieves state-of-the-art performance. Moreover, the prediction result is in accordance with that from the expert diagnosis.

11.
Curr Dev Nutr ; 5(10): nzab113, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34693193

RESUMO

Background: Increased maternal adiposity and inflammation have impacts on fetal growth. Objectives: The purpose of this prospective study was to investigate the associations of 3 proinflammatory adipokines in pregnancy with neonatal anthropometry. Methods: In a sample of 321 US pregnant women from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singleton Cohort (NCT00912132), plasma IL-6, fatty acid binding protein-4 (FABP4), and chemerin were measured in plasma samples collected at 10-14, 15-26, 23-31, and 33-39 weeks of gestation. Generalized linear models were used to estimate associations of adipokines with neonatal weight, thigh, and crown-heel length, and skinfolds at birth. Models adjusted for age, race/ethnicity, education, nulliparity, prepregnancy BMI, and weeks of gestation at blood collection. Results: At each time point, higher IL-6 was associated with lower neonatal birthweight and thigh length. At 15-26 weeks of gestation, a 1 SD pg/mL increase in IL-6 was associated with -84.46 g lower neonatal birthweight (95% CI: -150.70, -18.22), -0.17 cm shorter thigh length (95% CI: -0.27, -0.07), -0.43 cm shorter crown-heel length (95% CI: -0.75, -0.10), and -0.75 mm smaller sum of skinfolds (95% CI: -1.19, -0.31), with similar associations at 23-31 and 33-39 weeks of gestation. There were no associations of FABP4 and chemerin with neonatal anthropometry. Conclusions: Starting as early as 15 weeks of gestation, higher maternal IL-6 concentrations in pregnancy were associated with lower neonatal birthweight, thigh and crown-heel length, and skinfolds. These data provide insight into the relevance of maternal inflammatory markers with neonatal anthropometry.

12.
BMC Geriatr ; 21(1): 587, 2021 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-34674657

RESUMO

BACKGROUND: Few studies have explored patterns of physical activity (PA) and examined their relationship with depression among community-dwelling older adults. We aimed to identify the patterns of PA through a person-centered analytical approach and examine the association between quantity and patterns of PA, and depression among community-dwelling older adults. METHODS: We conducted a cross-sectional survey study in the Minhang district, Shanghai, China, in August 2019, and used a self-administered questionnaire to collect data through home visits. The total sample included 2525 older adults. This study used the Physical Activity Scale for the Elderly (PASE) to assess the quantity of PA in older adults. Depression was evaluated with the Geriatric Depression Scale (GDS). Latent class analysis (LCA) was used to identify subpopulations by shared item response patterns. Logistic regressions were performed to estimate the relationship between PASE score, patterns of PA, and depression. An exploratory analysis of joint levels and patterns of PA effects on depression was based on sample subgroups with combinations of levels and patterns of PA. Logistic regression was used to calculate the odds ratio for combined subgroups. RESULTS: Four latent classes were identified: "domestic types," "athletic types," "gardening/caring types," and "walkers." PASE scores and patterns of PA both were associated with depression. Older adults who were the most active (PASE quartile: 75-100%) and the athletic types had the strongest significant association with depression (OR = 0.19, 95% CI: 0.06-0.65), followed by those who were the most active (PASE quartile: 75-100%) and the walkers (OR = 0.28, 95% CI: 0.14-0.57) when compared with older adults with the least activity (PASE quartile: 0-25%) and domestic types. CONCLUSION: This study suggests both the quantity and patterns of physical activity are associated with depressive symptoms among community-dwelling older adults. Population-level intervention should encourage community-dwelling older adults to increase their quantity of PA to reduce the risk of depression. Athletics and walkers are recommended. To develop individual-level tailored interventions, more attention should be paid to older adults who are highly engaged in gardening/caring for others.


Assuntos
Depressão , Vida Independente , Idoso , China/epidemiologia , Estudos Transversais , Depressão/diagnóstico , Depressão/epidemiologia , Exercício Físico , Humanos
13.
J Chem Phys ; 155(14): 144701, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34654293

RESUMO

Metal nanoparticles are excellent acoustic resonators and their vibrational spectroscopy has been widely investigated. However, the coupling between vibrational modes of different nanoparticles is less explored. For example, how the intervening medium affects the coupling strength is not known. Here, we investigate how different polymers affect coupling in Au nanoplate-polymer-Au nanoplate sandwich structures. The coupling between the breathing modes of the Au nanoplates was measured using single-particle pump-probe spectroscopy, and the polymer dependent coupling strength was determined experimentally. Analysis of the acoustic mode coupling gives the effective spring constant for the polymers. A relative motion mode was also observed for the stacked Au nanoplates. The frequency of this mode is strongly correlated with the coupling constant for the breathing modes. The breathing mode coupling and relative motion mode were analyzed using a coupled oscillator model. This model shows that both these effects can be described using the same spring constant for the polymer. Finally, we present a new type of mass balance using the strongly coupled resonators. We show that the resonators have a mass detection limit of a few femtograms. We envision that further understanding of the vibrational coupling in acoustic resonators will improve the coupling strength and expand their potential applications.

14.
Ann N Y Acad Sci ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34480349

RESUMO

This study aims to establish a biological age (BA) predictor and to investigate the roles of lifestyles on biological aging. The 14,848 participants with the available information of multisystem measurements from the Dongfeng-Tongji cohort were used to estimate BA. We developed a composite BA predictor showing a high correlation with chronological age (CA) (r = 0.82) by using an extreme gradient boosting (XGBoost) algorithm. The average frequency hearing threshold, forced expiratory volume in 1 second (FEV1 ), gender, systolic blood pressure, and homocysteine ranked as the top five important features for the BA predictor. Two aging indexes, recorded as the AgingAccel (the residual from regressing predicted age on CA) and aging rate (the ratio of predicted age to CA), showed positive associations with the risks of all-cause (HR (95% CI) = 1.12 (1.10-1.14) and 1.08 (1.07-1.10), respectively) and cause-specific (HRs ranged from 1.06 to ∼1.15) mortality. Each 1-point increase in healthy lifestyle score (including normal body mass index, never smoking, moderate alcohol drinking, physically active, and sleep 7-9 h/night) was associated with a 0.21-year decrease in the AgingAccel (95% CI: -0.27 to -0.15) and a 0.4% decrease in the aging rate (95% CI: -0.5% to -0.3%). This study developed a machine learning-based BA predictor in a prospective Chinese cohort. Adherence to healthy lifestyles showed associations with delayed biological aging, which highlights potential preventive interventions.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34561801

RESUMO

Residential greenness exposure has been linked to a number of physical and mental disorders. Nevertheless, evidence on the association between greenness and geriatric depression was limited and focused on developed countries. This study was aimed to investigate whether the relationship between residential greenness exposure and geriatric depression exists among the elderly with long-term care insurance (LTCI) in Shanghai, China. In 2018, a total of 1066 LTCI elderly from a cross-sectional survey completed a questionnaire in Shanghai. Residential greenness indicators, including normalized difference vegetation index (NDVI) and soil-adjusted vegetation index (SAVI), were calculated from the Landsat 8 imagery data in different buffers (100-m, 300-m, and 500-m). Mediation analysis by perceived social support was conducted to explore potential mechanisms underlying the associations. In the fully adjusted model, one IQR increase of NDVI and SAVI in the 300-m buffer size was associated with an 11.9% (PR: 0.881, 95% CI: 0.795, 0.977) and 14.7% (PR: 0.853, 95% CI: 0.766, 0.949) lower prevalence of geriatric depression, respectively. Stronger association was observed in the elderly with lower education level, living in non-central area, and lower family monthly income. Perceived social support significantly mediated 40.4% of the total effect for NDVI 300-m buffer and 40.3% for SAVI 300-m buffer to the greenness-depression association, respectively. Our results indicate the importance of residential greenness exposure to geriatric depression, especially for the elderly with lower education level, living in non-central area, and lower family monthly income. Perceived social support might mediate the association. Well-designed longitudinal studies are warranted to confirm our findings and investigate the underlying mechanisms.

16.
AIDS Care ; : 1-8, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34581229

RESUMO

Few large studies evaluated the effects of time trends on virologic suppression in people living with HIV/AIDS (PLWHA) in China. To address this, An retrospective observational longitudinal study was conducted. We examined annual trends in the rate of virologic suppression, the viral load at the time of virologic suppression, and other determinants of virologic suppression in Zhejiang Province, China in PLWHA between January 2013 and July 2018. Patients who received a treatment regimen for at least 24 weeks were included. Virologic suppression was defined as VL ≤50 copies/mL. Generalized estimating equation logistic regression models were used to adjust for covariates. We included 16,265 patients with 45023 tests. The proportion of patients who experienced an unsuccessful virologic outcome decreased continuously throughout the observation period (18.14% to 6.64%). Time was significantly negatively associated with detectable VL (all ORs <1). Other factors were positively associated with detectable VL, including patients <30 years of age, single, non-adherent to treatment, and with a follow-up CD4 count <200 cells/µL. Patients infected through homosexual transmission and those with a longer ART duration were more likely to reach virologic suppression. We demonstrated outstanding time trend improvements in the virological outcomes of PLWHA in China.

17.
Am J Clin Nutr ; 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34510175

RESUMO

BACKGROUND: Emerging evidence suggests beneficial impacts of plant-based diets on glucose metabolism among generally healthy individuals. Whether adherence to these diets is related to risk of gestational diabetes mellitus (GDM) is unknown. OBJECTIVES: We aimed to examine associations between plant-based diets and GDM in a large prospective study. METHODS: We included 14,926 women from the Nurses' Health Study II (1991-2001), who reported ≥1 singleton pregnancy and without previous GDM before the index pregnancy. Prepregnancy adherence to plant-based diets was measured by an overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI) as assessed by FFQs every 4 y. Incident first-time GDM was ascertained from a self-reported physician diagnosis, which was previously validated by review of medical records. We used log-binomial models with generalized estimating equations to calculate RRs and 95% CIs for associations of PDIs with GDM. RESULTS: We documented 846 incident GDM cases over the 10-y follow-up among 20,707 pregnancies. Greater adherence to the PDI and hPDI was associated with lower GDM risk. For the PDI, the multivariable-adjusted RR (95% CI) comparing the highest and lowest quintiles (Q5 compared with Q1) was 0.70 (0.56, 0.87) (Ptrend = 0.0004), and for each 10-point increment was 0.80 (0.71, 0.90). For the hPDI, the RR (95% CI) of Q5 compared with Q1 was 0.75 (0.59, 0.94) (Ptrend = 0.009) and for each 10-point increment was 0.86 (0.77, 0.95). After further adjustment for prepregnancy BMI, the associations were attenuated but remained significant: for the PDI, the RR (95% CI) for each 10-point increment was 0.89 (0.79, 1.00) and the corresponding RR (95% CI) was 0.89 (0.80, 0.99) for the hPDI. The uPDI was not associated with GDM. CONCLUSIONS: Our study suggests that greater prepregnancy adherence to a healthful plant-based diet was associated with lower risk of GDM, whereas an unhealthful plant-based diet was not related to GDM risk.

18.
J Periodontal Res ; 56(6): 1200-1212, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34492118

RESUMO

BACKGROUND AND OBJECTIVE: Cementum is a part of the periodontium and anchors periodontal ligaments to the alveolar bone. Cementoblasts are responsible for the cementum formation via matrix deposition and subsequently mineralization. Thus, exploring novel mechanisms underlying the function of cementoblast contributes to the treatment of cementum damage. Recently, circRNA Lrp6 (circLRP6) has been of interest due to its active role in cell differentiation, but its potential role in cementoblast differentiation remains unclear. Herein, we attempted to elucidate the role of circLRP6 in cementoblast differentiation and clarify any associated mechanisms. MATERIAL AND METHODS: The mRNA expressions of circLRP6, miR-145a-5p, zinc finger E-box binding homeobox 2 (Zeb2), runt-related transcription factor 2 (Runx2), osteopontin (Opn), and bone sialoprotein (Bsp) were evaluated by qRT-PCR. The protein levels of Zeb2 were measured by Western blot. Bioinformatic analysis and dual-luciferase reporter assays were used to test the potential binding targets of miR-145a-5p. The differentiation potentials of the cementoblasts were assessed by Alkaline phosphatase (ALP) staining, ALP activity assay, Alizarin red S (ARS) staining, and quantification. RESULTS: In this study, circLRP6 was significantly upregulated in cementoblast differentiation. Furthermore, circLRP6 knockdown inhibited ALP levels, reduced calcium nodule formation and the expression of Runx2, Opn, and Bsp. Mechanically, bioinformatic analysis and dual-luciferase reporter assays confirmed miR-145a-5p was a potential binding target of circLRP6. miR-145a-5p can negatively regulate cementoblast differentiation. Subsequently, bioinformatic analysis and dual-luciferase reporter assays confirmed Zeb2 was a potential miR-145a-5p target. miR-145a-5p overexpression resulted in a downregulation of Zeb2. Furthermore, Zeb2 inhibition partially reversed the effect of circLRP6 during cementoblast differentiation. CONCLUSION: Taken together, circLRP6 appears to modulate cementoblast differentiation by antagonizing the function of miR-145a-5p, thereby increasing Zeb2. This study serves as a stepping stone for the potential development of an approach to promote cementum formation.


Assuntos
Cemento Dentário , MicroRNAs , Diferenciação Celular , MicroRNAs/genética , Ligamento Periodontal , RNA Circular
19.
Nutrients ; 13(9)2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34578958

RESUMO

Amino acids, fatty acids, and acylcarnitine metabolites play a pivotal role in maternal and fetal health, but profiles of these metabolites over pregnancy are not completely established. We described longitudinal trajectories of targeted amino acids, fatty acids, and acylcarnitines in pregnancy. We quantified 102 metabolites and combinations (37 fatty acids, 37 amino acids, and 28 acylcarnitines) in plasma samples from pregnant women in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons cohort (n = 214 women at 10-14 and 15-26 weeks, 107 at 26-31 weeks, and 103 at 33-39 weeks). We used linear mixed models to estimate metabolite trajectories and examined variation by body mass index (BMI), race/ethnicity, and fetal sex. After excluding largely undetected metabolites, we analyzed 77 metabolites and combinations. Levels of 13 of 15 acylcarnitines, 7 of 25 amino acids, and 18 of 37 fatty acids significantly declined over gestation, while 8 of 25 amino acids and 10 of 37 fatty acids significantly increased. Several trajectories appeared to differ by BMI, race/ethnicity, and fetal sex although no tests for interactions remained significant after multiple testing correction. Future studies merit longitudinal measurements to capture metabolite changes in pregnancy, and larger samples to examine modifying effects of maternal and fetal characteristics.


Assuntos
Gravidez/sangue , Adolescente , Adulto , Aminoácidos/sangue , Índice de Massa Corporal , Carnitina/análogos & derivados , Carnitina/sangue , Grupos de Populações Continentais/estatística & dados numéricos , Ácidos Graxos/sangue , Feminino , Humanos , Masculino , Metabolômica , Gravidez/etnologia , Trimestres da Gravidez/sangue , Estudos Prospectivos , Estados Unidos , Adulto Jovem
20.
Nat Genet ; 53(9): 1348-1359, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34493867

RESUMO

Lung cancer in never smokers (LCINS) is a common cause of cancer mortality but its genomic landscape is poorly characterized. Here high-coverage whole-genome sequencing of 232 LCINS showed 3 subtypes defined by copy number aberrations. The dominant subtype (piano), which is rare in lung cancer in smokers, features somatic UBA1 mutations, germline AR variants and stem cell-like properties, including low mutational burden, high intratumor heterogeneity, long telomeres, frequent KRAS mutations and slow growth, as suggested by the occurrence of cancer drivers' progenitor cells many years before tumor diagnosis. The other subtypes are characterized by specific amplifications and EGFR mutations (mezzo-forte) and whole-genome doubling (forte). No strong tobacco smoking signatures were detected, even in cases with exposure to secondhand tobacco smoke. Genes within the receptor tyrosine kinase-Ras pathway had distinct impacts on survival; five genomic alterations independently doubled mortality. These findings create avenues for personalized treatment in LCINS.


Assuntos
Variações do Número de Cópias de DNA/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , não Fumantes/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Receptores ErbB/genética , Feminino , Genoma/genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Receptores Androgênicos/genética , Fatores de Risco , Fumar/genética , Enzimas Ativadoras de Ubiquitina/genética , Sequenciamento Completo do Genoma , Adulto Jovem
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