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1.
Environ Res ; 187: 109645, 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32422484

RESUMO

Exposure to lead (Pb) and cadmium (Cd) were related to lung function impairment, and this association may be modified by genetic variants in oxidative stress response. Here we enrolled 1243 coke-oven workers in a prospective cohort who were followed up from 2010 to 2014, assessed the associations of Pb and Cd exposure with 4-year lung function impairment, and further explored the interaction effects of Pb with 2664 single nucleotide polymorphisms (SNPs) in 345 oxidative stress related genes. Urinary levels of Pb, Cd, and two oxidative stress biomarkers [8-iso-prostaglandin F2α (8-iso-PGF2α) for lipid peroxidation and 8-hydroxy-2'-deoxyguanosine (8-OHdG) for oxidative DNA damage] were measured at baseline only and their lung function levels were measured both at baseline and at the end of follow-up. Each 10-fold increase in urinary Pb was associated with -159 (95%CI: -254, -64.2) mL and -3.63% (95%CI: -6.48%, -0.78%) changes in FEV1 and percent predicted FEV1 (ppFEV1), respectively. But none significant associations were observed for Cd. NQO1 rs2917670 showed significant interaction with Pb on elevated FEV1 decline after multiple comparison (Pint=1.54 × 10-5). In addition, urinary Pb increased with 8-iso-PGF2α and the rs2917670-C could significantly decrease NQO1 expression in normal lung tissues. These findings suggested the gene-environmental interaction of NQO1 rs2917670 and Pb exposure on the reduction of FEV1. The effect of Pb exposure on elevated oxidative stress and the decreased expression of antioxidant enzyme NQO1 caused by rs2917670-C allele may partly explain the underlying biological mechanism.

2.
Environ Int ; 140: 105762, 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32380304

RESUMO

OBJECTIVE: Telomere is required for maintaining chromosome stability and genome integrity, while telomere length is sensitive to environmental stressors. We aimed to identify the effects of multiple metals co-exposure as well as their joint effects with TERT-CLPTM1L variants on leukocyte telomere length (LTL). METHODS: This study included 842 workers from a coke-oven plant, of whom plasma concentrations of 23 metals and LTL were determined. Genetic variations in TERT-CLPTM1L were genotyped by using the Global Screening Array. Multipollutant-based statistical methods, including the Bonferroni-correction, backward elimination procedure, and LASSO penalized regression analysis, were used to select the LTL-associated metals. Generalized linear regression models were used to evaluate the joint effects of TERT-CLPTM1L variants with positive metal on LTL. RESULTS: Each 1% increase in plasma concentration of manganese (Mn) was significantly associated with a 0.153% increase in LTL [ß(95%CI) = 0.153(0.075, 0.230), P < 0.001] in single-metal models after Bonferroni-correction. The multiple-metal models and the LASSO penalized regression analysis both indicated Mn as the sole significant predictor for LTL. Furthermore, 5 tagSNPs (rs33954691, rs6554759, rs465498, rs2455393, and rs31489) in TERT-CLPTM1L with high plasma Mn (>4.21 µg/L) showed joint effects on increasing LTL. CONCLUSIONS: Our study revealed the independent and positive association between plasma Mn and LTL when accounting for co-exposure to other metals. This effect can be further enhanced by TERT-CLPTM1L variants. These results may advance our understanding of the complex interplay between genetic and environmental factors on telomere length. Further experimental studies are warranted to elucidate the underlying mechanisms.

3.
J Hazard Mater ; 395: 122660, 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32344298

RESUMO

Gestation and lactation are very sensitive and vulnerable stages for human growth and development. During these two periods, short-chain chlorinated paraffins (SCCPs) and medium-chain chlorinated paraffins (MCCPs) can be transported to neonates via transplacental and breastfeeding transfers, and eventually posing potential adverse effects to neonates. Up to date, no simultaneous investigation of prenatal and postnatal exposure of CPs is reported. To bridge this knowledge gap, we have analyzed SCCPs and MCCPs in 20 complete sets of maternal serum, umbilical cord serum, placenta, and breast milk. The levels of both ∑SCCP and ∑MCCP followed the order of maternal serum > breast milk > cord serum > placenta. The breastfeeding transfer ratios (RBM, ≈ 1.0) of CPs were greater than the corresponding transplacental transfer ratios (RCM, < 1.0), demonstrating the higher transport of CPs during the lactation period. The placental retention/or accumulation ratios (RPM) showed that CPs were effectively retained by the placental barrier. Furthermore, the total exposure amount of SCCPs and MCCPs during the lactation period was> 100 times higher than the gestation exposure amounts. This study helps to better understand the prenatal and postnatal exposure of CPs and provides a solid basis for accurate human health risk assessment of CPs.

4.
Sci Total Environ ; 726: 138526, 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32304943

RESUMO

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP), a widely used organophosphorus flame retardant, has been frequently detected in the environment including indoor dust. Long-term exposure to TDCPP-containing dust may adversely affect human skin, however, little is known about its potential cytotoxicity. In this study, human skin keratinocytes (HaCaT) were employed to study TDCPP-induced cytotoxicity and associated mechanisms. The effects of TDCPP on cell morphology, viability, apoptosis, and cycle, and the mRNA levels of apoptosis (Bcl-2, Bax and Caspase-3) and cell cycle (cyclin D1, CDK2, CDK4 and CDK6) regulatory genes were investigated. The results showed that TDCPP caused a concentration-dependent decrease in cell viability after exposing to TDCPP ≥100 µg/mL for 48 h, with a median lethal concentration of 163 µg/mL (LC50). In addition, TDCPP induced cell apoptosis and arrested cell cycle in the G0/G1 phase at 16 and 160 µg/mL by enhancing Bax and Caspase-3 expression besides inhibiting cyclin D1, CDK2, CDK6 and Bcl-2 expression. Our results showed that TDCPP-induced toxicity in HaCaT cells was probably through cell apoptosis and cell cycle arrest. This study provides information on the toxicity of TDCPP to human skin cells, which may help to reduce its toxicity to human skin.

5.
Radiother Oncol ; 147: 130-135, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32294606

RESUMO

BACKGROUND: To assess the relationship between the level of clinical radiation oncologist and the prognosis of patients with nasopharyngeal carcinoma (NPC). To our knowledge, no previous study has explicitly assessed the relationship with cancer prognosis and clinical radiation oncologists level. The effect of physicians on the prognosis has been entirely ignored. METHODS: Clinical data were collected for 1140 patients with newly diagnosed NPC. Based on the 3-year overall survival, the treating physicians were classified into 3 grades: high-level group, medium-level group, and low-level group. Cox proportional hazards regression analysis was used to assess the independent significance of different prognostic factors. Propensity score matching (PSM) was used to minimize the influence of confounders so that difference in outcomes provides an unbiased estimate of the influence of physician. Interactive Risk Attributable Program (IRAP) was used to calculate the attribution risk of individual risk factors or a combination of multiple factors. RESULTS: The 3-year OS in the high-level, medium-level, and low-level groups was 92.9%, 87.7%, and 83.5%, respectively (p = 0.003). After propensity score matching, the 3-year OS was 92.4%, 87.4%, and 82.9%, respectively (p = 0.004). IRAP was used to calculate the attribution risk of mortality risk. After multivariable adjustment, patient-related factors including tumor accounted for 90.02% [95% confidence interval (CI), 73.43-96.84%) and physician factors accounted for 17.66% (95% CI, 5.39-44.65%) of the mortalityrisk. All related factors, including patient-related factors and physician factors accounted for 92.02% (95% CI, 77.83-97.43%). CONCLUSION: Our study demonstrated obvious differences in the prognosis of patients treated by various clinical radiation oncologists. The largest share of prognosis risk was found to be at the patient level, while variation in prognosis was, in part, attributable to differences among physicians.

6.
Lancet Diabetes Endocrinol ; 8(4): 292-300, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32135135

RESUMO

BACKGROUND: The timepoint at which fetal growth begins to differ by maternal glycaemic status is not well understood. To address this lack of data, we examined gestational diabetes, impaired glucose tolerance, and early pregnancy glucose concentrations in relation to fetal growth trajectories. METHODS: This cohort study included 2458 pregnant women from the NICHD Fetal Growth Studies-Singletons study, which took place between 2009 and 2013. Women were recruited from 12 clinical centres in the USA. Women aged 18-40 years without major chronic conditions when entering pregnancy were included and those with records of neither glucose screening test or glucose tolerance test were excluded from the study. Women were enrolled at gestational weeks 8-13 and randomly assigned to four ultrasonogram schedules (Group A; weeks 16, 24, 30, 34; Group B: weeks 18, 26, 31, 35, 39; Group C: weeks 20, 28, 32, 36; Group D: weeks 22, 29, 33, 37, 41) to capture weekly fetal growth. Gestational diabetes, impaired glucose tolerance, and normal glucose tolerance were defined by medical record review. Glucose was measured in a subsample of women at weeks 10-14. We modelled fetal growth trajectories using linear mixed models with cubic splines. This study is registered with ClinicalTrials.gov, NCT00912132. FINDINGS: Of the 2458 women included in this study, 107 (4·4%) had gestational diabetes, 118 (4·8%) had impaired glucose tolerance, and 2020 (82·2%) had NGT. 213 women were excluded from the main analysis. The cohort with gestational diabetes was associated with a larger estimated fetal weight that started at week 20 and was significant at week 28-40 (at week 37: 3061 g [95% CI 2967-3164] for women with gestational diabetes vs 2943 g [2924-2962] for women with normal glucose tolerance, adjusted p=0·02). In addition, glucose levels at weeks 10-14 were positively associated with estimated fetal weight starting at week 23 and the association became significant at week 27 (at week 37: 3073 g [2983-3167] in the highest tertile vs 2853 g [2755-2955] in the lowest tertile, adjusted p=0·0009. INTERPRETATION: Gestational diabetes was associated with a larger fetal size that started at week 20 and became significant at gestational week 28. Efforts to mitigate gestational diabetes-related fetal overgrowth should start before 24-28 gestational weeks, when gestational diabetes is typically screened for in the USA. FUNDING: National Institutes of Health.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32180760

RESUMO

Objective: Prolactin and progesterone are implicated in glucose homeostasis in and outside of pregnancy. However, their associations with gestational diabetes (GDM) risk were not well-understood. This study investigates this question in a prospective and longitudinal cohort. Methods: This is a nested case-control study of 107 incident GDM cases and 214 matched non-GDM controls within the NICHD Fetal Growth Studies-Singleton Cohort. Blood samples were collected at gestational weeks 10-14, 15-26, 23-31, and 33-39. The odds ratios (OR) of GDM were estimated using conditional logistic regression. The longitudinal changes in prolactin and progesterone were estimated using linear mixed-effects models. Results: Compared to controls, cases have significantly higher prolactin levels at weeks 10-14 (median: 50.4 vs. 42.1 ng/mL), and significantly lower progesterone levels at weeks 10-14 (median: 109.4 vs. 126.5 nmol/L). Prolactin levels at weeks 10-14 were significantly and positively associated with GDM risk; the adjusted ORs across increasing quartiles were 1.00, 1.13, 1.80, 2.33 (p-trend = 0.02). A similar but slightly attenuated association was observed at weeks 15-26 (p-trend = 0.05). Progesterone was not associated with GDM risk at either time points. Longitudinal changes in prolactin and progesterone between the first two visits were not associated with GDM risk. In addition, prolactin was significantly and positively associated with insulin and C-peptide levels at weeks 10-14, and significantly and inversely associated with C-peptide levels at weeks 15-26; progesterone was significantly and inversely associated with glucose and insulin levels. Conclusions: This study provided the first prospective evidence of a positive association between prolactin levels in early pregnancy and GDM risk.

8.
J Am Geriatr Soc ; 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32222105

RESUMO

BACKGROUND: Older migrants in China without local resident registration (hukou) are a vulnerable population and face barriers to receiving local healthcare. OBJECTIVES: We aimed to quantify the disparities in healthcare utilization between older migrants and local residents in Shanghai, China. DESIGN: This was a cross-sectional study. SETTING: The study was conducted in Shanghai, China, in 2016. PARTICIPANTS: Older adults (aged ≥60 years) were recruited based on a three-stage stratified cluster sampling method (2571 older locals and 1920 older migrants). MEASUREMENTS: We compared utilization of outpatient care, inpatient care, preventive care, emergency room (ER) admission, and dental care, as well as medication use between older migrants and local residents. The local-migrant gap was parsed into observed and unobserved components using the Blinder-Oaxaca decomposition method. RESULTS: Older migrants were less likely to utilize outpatient (odds ratio [OR] = 0.757; 95% confidence interval [CI] = 0.617-0.928), inpatient (OR = 0.642; 95% CI = 0.443-0.931), and preventive care (OR = 0.743; 95% CI = 0.643-0.858) and were more likely to use medication (OR = 1.254; 95% CI = 1.089-1.445) than local residents. Differences in ER admissions and dental care utilization were not significant in the regression analysis. The decomposition results indicated that 55% and 71% of the local-migrant gap in outpatient and preventive care utilization were attributable to individual characteristics, like health insurance. Unobserved components, including hukou-related factors and personal heterogeneous preferences, contributed 59% and 63% to utilization of inpatient care and medication use, respectively. CONCLUSION: We identified local-migrant gaps in healthcare utilization among older adults in China. Further research is needed into integration of the health insurance system, accessibility of public health welfare benefits, and reconstruction of social networks among older migrants.

9.
Chemosphere ; 252: 126431, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32208197

RESUMO

The significant removal efficiency of microcystis aeruginosa was presented using Pt/Ti anode and activated carbon fiber/nickel foam (ACF/Ni) cathode by addition of Fe2+ slightly in a wide range of initial pH (3-9). Results showed that about 93% of the Microcystis aeruginosa cells were removed within 15 min for Pt/Ti-ACF/Ni-Fe2+ system. Dosage of Fe2+, current density, and initial pH had remarkable effects on the removal efficiency of microcystis aeruginosa. The mechanism of algae removal in the Pt/Ti-ACF/Ni-Fe2+ electrochemical system was revealed by the comparison between Pt/Ti-ACF/Ni-Fe2+ process and classical Fenton process, the analysis on Microcystis aeruginosa and ACF/Ni by SEM, the specific surface area and pore size analysis of ACF, and the determination of UV254, OD620 and microcystin-LR (MC-LR). Results showed that the main mechanism of this system was the electro-Fenton process, which was accompanied by electro-adsorption, electro-floatation, and electro-coagulation process. And the cooperation mechanism on the electrochemical removal system was further speculated. With the breakdown of algal cells during the electrolysis, the MC-LR and other substances released from the cells were effectively degraded. Besides, the new cathode exhibited favorable and stable reusability. This study built up a high-efficiency algae removal system, which broke through the limits of narrow working pH range and large consumption of exogenous chemicals in electro-Fenton process.

10.
Diabetes Care ; 43(4): 793-798, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32041900

RESUMO

OBJECTIVE: We examined the association of lactation duration with incident type 2 diabetes among women with a history of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: We monitored 4,372 women with a history of GDM participating in the Nurses' Health Study II for incident type 2 diabetes over 25 years up to 2017. Lactation history was obtained through follow-up questionnaires to calculate lactation duration. Follow-up blood samples were collected from a subset of these women at median age of 58 years through the Diabetes & Women's Health Study. RESULTS: We documented 873 incident cases of type 2 diabetes during 87,411 person-years of follow-up. Longer duration of lactation was associated with lower risk of type 2 diabetes for both total lactation (hazard ratio 1.05 [95% CI 0.83-1.34] for up to 6 months, 0.91 [0.72-1.16] for 6-12 months, 0.85 [0.67-1.06] for 12-24 months, and 0.73 [0.57-0.93] for >24 months, compared with 0 months; P-trend = 0.003) and exclusive breastfeeding (P-trend = 0.002) after adjustment for age, ethnicity, family history of diabetes, parity, age at first birth, smoking, diet quality, physical activity, and prepregnancy BMI. Longer duration of lactation was also associated with lower HbA1c, fasting plasma insulin, and C-peptide concentrations among women without type 2 diabetes at follow-up (all adjusted P-trend ≤0.04). CONCLUSIONS: Longer duration of lactation is associated with a lower risk of type 2 diabetes and a favorable glucose metabolic biomarker profile among women with a history of GDM. The underlying mechanisms and impact on diabetes complications, morbidity, and mortality remain to be determined.

11.
Pharmazie ; 75(1): 18-22, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-32033628

RESUMO

Salvia miltiorrhiza (Danshen) is typically used in the treatment of diabetic complications and is often co-prescribed with gliquidone in China. However, whether danshen affects the absorption of gliquidone has not been elucidated. In this study, the effects of an aqueous extract of danshen (danshen injection, DSI) and its primary compounds (danshensu, protocatechuic aldehyde, rosmarinic acid and salvianolic acid B) on gliquidone transport across Caco-2 monolayer cells was investigated. DSI enhanced the transport of gliquidone in Caco-2 cell monolayers from the apical (AP) to basolateral (BL) sides and from the BL to AP sides. Rosmarinic acid (RA) also significantly increased the Papp (AP-BL) value for gliquidone transport. Verapamil (a P-gp inhibitor) and Ko143 (a BCRP inhibitor) inhibited the BL-AP transport of gliquidone and promoted the AP-BL transport of gliquidone, whereas MK571 (an MRP1 inhibitor), probenecid (an MRP2 inhibitor), and benzbromarone (an MRP3 inhibitor) had no effect on gliquidone transport. RA also enhanced the intracellular accumulation of Rho123 and Hoechst 33342. The expression of P-gp and BCRP was significantly downregulated, and P-gp ATPase activity was promoted by RA in a dose-dependent manner. These results indicate that an aqueous extract of danshen can increase the transport of gliquidone in Caco-2 cell monolayers and that RA may be the primary compound associated with this activity, which is in agreement with RA simultaneously suppressing the function and expression of P-gp and BCRP.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31958311

RESUMO

OBJECTIVE: Women with a history of gestational diabetes mellitus (GDM) have an exceptionally high risk for type 2 diabetes (T2D). Yet, little is known about genetic determinants for T2D in this population. We examined the association of a genetic risk score (GRS) with risk of T2D in two independent populations of women with a history of GDM and how this association might be modified by non-genetic determinants for T2D. RESEARCH DESIGN AND METHODS: This cohort study included 2434 white women with a history of GDM from the Nurses' Health Study II (NHSII, n=1884) and the Danish National Birth Cohort (DNBC, n=550). A GRS for T2D was calculated using 59 candidate single nucleotide polymorphisms for T2D identified from genome-wide association studies in European populations. An alternate healthy eating index (AHEI) score was derived to reflect dietary quality after the pregnancy affected by GDM. RESULTS: Women on average were followed for 21 years in NHSII and 13 years in DNBC, during which 446 (23.7%) and 155 (28.2%) developed T2D, respectively. The GRS was generally positively associated with T2D risk in both cohorts. In the pooled analysis, the relative risks (RRs) for increasing quartiles of GRS were 1.00, 0.97, 1.25 and 1.19 (p trend=0.02). In both cohorts, the association appeared to be stronger among women with poorer (AHEI

13.
J Ren Nutr ; 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31959496

RESUMO

OBJECTIVE: Nut intake has been associated with reduced cardiometabolic risk, but few studies have examined its association with renal function. We examined associations between nut intake and renal function among women with previous gestational diabetes mellitus (GDM), a population with an increased risk for renal dysfunction. DESIGN AND METHODS: This study included 607 women with a history of GDM who participated in the Diabetes & Women's Health Study (2012-2014) follow-up clinical examination in Denmark. At the clinic, biospecimens were collected, and habitual intake of nuts (9 types) in the past year was assessed using a food frequency questionnaire. A total of 330 women free of major chronic diseases were included in the analysis. Total nut intake was classified as none (≤1 serving/month), monthly (2-3 servings/month), weekly (1-6 servings/week), and daily (≥1 serving/day). One serving was defined as 28 g. Renal function markers included estimated glomerular rate (eGFR) and urinary albumin-to-creatinine ratio (UACR), calculated based on plasma creatinine (mg/dL), and urinary albumin (mg/L), and creatinine (mg/dL) measurements, respectively. We estimated percent differences with 95% confidence intervals for each outcome by nut intake, adjusted for current body mass index, age, physical activity, energy intake, alcohol consumption, and vegetables intake. RESULTS: We observed a nonlinear association between total nut intake and UACR with lowest UACR values among women with weekly intake. Compared to women with weekly intake (n = 222), the adjusted UACR values were higher by 86% [95% confidence interval: 15%, 202%], 24% [-1%, 54%], and 117% [22%, 288%] among women with no (n = 13), monthly (n = 86), and daily (n = 9) intake, respectively. Compared to weekly consumers, daily nut consumers also had 9% [0%, 19%] significantly higher eGFR values, but eGFR values were similar among women with no and monthly intake. CONCLUSION: Moderate nut consumption may be beneficial to kidney health among women with prior GDM.

14.
Neuroscience ; 429: 78-91, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31917345

RESUMO

Enkephalin (ENK) has been implicated in pain modulation within the spinal dorsal horn (SDH). Revealing the mechanisms underlying ENK analgesia entails the anatomical and functional knowledge of spinal ENK-ergic circuits. Herein, we combined morphological and electrophysiological studies to unravel local ENK-ergic circuitry within the SDH. First, the distribution pattern of spinal ENK-ergic neurons was observed in adult preproenkephalin (PPE)-GFP knock-in mice. Next, the retrograde tracer tetramethylrhodamine (TMR) or horseradish peroxidase (HRP) was injected into the parabrachial nucleus (PBN) in PPE-GFP mice. Immunofluorescent staining showed I-isolectin B4 (IB4) labeled non-peptidergic afferents were in close apposition to TMR-labeled PBN-projecting neurons within lamina I as well as PPE-immunoreactivity (-ir) neurons within lamina II. Some TMR-labeled neurons were simultaneously in close association with both IB4 and PPE-ir terminals. Synaptic connections of these components were further confirmed by electron microscopy. Finally, TMR was injected into the PBN in adult C57BL/6 mice. Whole-cell patch recordings showed that δ-opioid receptor (DOR) agonist, [D-Pen2,5]-enkephalin (DPDPE, 1 µM), significantly reduced the frequency of miniature excitatory postsynaptic current (mEPSC) and decreased the activity of TMR-labeled neurons. In conclusion, spinal ENKergic neurons receive direct excitatory inputs from primary afferents, which might be directly recruited to release ENK under the condition of noxious stimuli; ENK could inhibit the glutamatergic transmission towards projecting neurons via presynaptic and postsynaptic DORs. These morphological and functional evidence may explain the mechanisms underlying the analgesic effects exerted by ENK within the SDH.

15.
Mol Pharm ; 17(1): 338-348, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31793786

RESUMO

The synergy of chemotherapy and antiangiogenesis therapy is a new strategy for cancer treatment. In this paper, a well-developed core-shell nanoparticle loaded with gambogic acid (GA), heparin (HP), and the immunoadjuvant cytosine-phosphate-guanine oligonucleotide (CpG ODN), called GHC NP, was constructed to treat hepatocellular carcinoma. GHC NPs with liver targeting activity can effectively inhibit tumor cell proliferation and angiogenesis. With the delivery of nanocarriers and the assistance of GA and HP, the GHC NPs can more effectively upregulate cytotoxic T cell (CTL) levels, promote helper T cell (Th cell) differentiation, and induce Th1 immune responses in long-term treatment compared with single CpG ODN. This synergistically enhanced immunotherapy might have universal application in cancer treatments.

16.
J Colloid Interface Sci ; 561: 93-103, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31812870

RESUMO

Highly sensitive wearable textile pressure sensors represent the key components of smart textiles and personalized electronics, with potential applications in biomedical monitoring, electronic skin, and human-machine interfacing. Here, we present a simple and low-cost strategy to fabricate highly sensitive wearable textile pressure sensors for non-invasive human motion and physiological signal monitoring and the detection of dynamic tactile stimuli. The wearable textile sensor was woven using a one-dimensional (1D) weavable core-sheath nanofiber yarn, which was obtained by coating a Ni-coated cotton yarn electrode with carbon nanotube (CNT)-embedded polyurethane (PU) nanofibers using a simple electrospinning technique. In our design, the three-dimensional elastic porous nanofiber structure of the force-sensing layer and hierarchical fiber-bundled structure of the conductive Ni-coated electrode provide the sensor with a relatively large surface area, and a sufficient surface roughness and elasticity. This leads to rapid and sharp increases in the contact area under stimuli with low external pressure. As a result, the textile pressure sensor exhibits the advantages of a high sensitivity (16.52 N-1), wide sensing range (0.003-5 N), and short response time (~0.03 s). Owing to these merits, our textile-based sensor can be directly attached to the skin as usual and conformally fit the shape deformations of the body's complex flexible curved surfaces. This contributes to the reliable real-time monitoring of human movements, ranging from subtle physiological signals to vigorous movements. Moreover, a large-area textile sensing matrix is successfully fabricated for tactile mapping of spatial pressure by being worn on the surface of wrist, highlighting the tremendous potential for applications in smart textiles and wearable electronics.

17.
Jpn J Clin Oncol ; 50(2): 159-168, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-31711182

RESUMO

OBJECTIVE: To view and evaluate the prognosis factors in patients with nasopharyngeal carcinoma (NPC) treated with intensity modulated radiation therapy using nomogram and decision curve analysis (DCA). METHODS: Based on a primary cohort comprising consecutive patients with newly confirmed NPC (n = 1140) treated between January 2014 and December 2015, we identified independent prognostic factors of overall survival (OS) to establish a nomogram. The model was assessed by bootstrap internal validation and external validation in an independent validation cohort of 460 patients treated between January 2013 and December 2013. The predictive accuracy and discriminative ability were measured by calibration curve, concordance index (C-index) and risk-group stratification. The clinical usefulness was assessed by DCA. RESULTS: The nomogram incorporated T-stage, N-stage, age, concurrent chemotherapy and primary tumour volume (PTV). The calibration curve presented good agreement for between the nomogram-predicted OS and the actual measured survival probability in both the primary and validation cohorts. The model showed good discrimination with a C-index of 0.741 in the primary cohort and 0.762 in the validation cohort. The survival curves of different risk-groups were separated clearly. Decision curve analysis demonstrated that the nomogram provided a higher net benefit (NB) across a wider reasonable range of threshold probabilities for predicting OS. CONCLUSION: This study presents a predictive nomogram model with accurate prediction and independent discrimination ability compared with combination of T-stage and N-stage. The results of DCA supported the point that PTV can help improve the prognostic ability of T-stage and should be added to the TNM staging system.

18.
Cell Prolif ; 53(1): e12697, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31713930

RESUMO

OBJECTIVES: miR-21 can promote osteoblast differentiation of periodontal ligament stem cells. However, the effect of miR-21 on bone remodelling in the midpalatal suture is unclear. This study aimed to elucidate the effects of miR-21 on the midpalatal suture bone remodelling by expanding the palatal sutures. MATERIALS AND METHODS: miR-21 deficient (miR-21-/- ) and wild-type (WT) mice were used to establish animal models by expanding the palatal sutures. Micro-CT, haematoxylin-eosin (HE) staining, tartrate-resistant acid phosphatase (TRAP) staining, fluorescence labelling and immunohistochemistry were used to investigate the function of miR-21 in midpalatal suture bone remodelling. Besides, bone mesenchymal stem cells (BMSCs) derived from both miR-21-/- and WT mice were cultured. The MTT, CCK8, EdU analysis, transwell and wound healing test were used to assess the effects of miR-21 on the characteristics of cells. RESULTS: The expression of ALP was suppressed in miR-21-/- mice after expansion except 28 days. The expression of Ocn in WT mice was much higher than that of miR-21-/-  mice. Besides, with mechanical force, miR-21 deficiency downregulated the expression of Opg, upregulated the expression of Rankl, and induced more osteoclasts as TRAP staining showed. After injecting agomir-21  to miR-21-/- mice, the expression of Alp, Ocn and Opg/Rankl were rescued. In vitro, the experiments suggested that miR-21 deficiency reduced proliferation and migration ability of BMSCs. CONCLUSIONS: The results showed that miR-21 deficiency reduced the rate of bone formation and prolonged the process of bone formation. miR-21 regulated the bone resorption and osteoclastogenesis by affecting the cell abilities of proliferation and migration.


Assuntos
Células da Medula Óssea/metabolismo , Remodelação Óssea , Suturas Cranianas/metabolismo , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismo , Palato/metabolismo , Estresse Mecânico , Animais , Células da Medula Óssea/citologia , Diferenciação Celular , Proliferação de Células , Suturas Cranianas/citologia , Regulação da Expressão Gênica , Células-Tronco Mesenquimais/citologia , Camundongos , Camundongos Knockout , MicroRNAs/genética , Osteoprotegerina/biossíntese , Osteoprotegerina/genética , Palato/citologia , Ligante RANK/biossíntese , Ligante RANK/genética , Fosfatase Ácida Resistente a Tartarato/biossíntese , Fosfatase Ácida Resistente a Tartarato/genética
19.
Environ Pollut ; 258: 113655, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31818624

RESUMO

Mosaic loss of chromosome Y (mLOY) is the most common structure somatic event that related to increased risks of various diseases and mortality. Environmental pollution and genetic susceptibility were important contributors to mLOY. We aimed to explore the associations of polycyclic aromatic hydrocarbons (PAHs) exposure, as well as their joint effects with age, smoking, and genetic variants on peripheral blood mLOY. A total of 1005 male coke-oven workers were included in this study and their internal PAHs exposure levels of 10 urinary PAH metabolites and plasma benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydotetrol-albumin (BPDE-Alb) adducts were measured. mLOY was defined by the median log R ratio(mLRR) of 1480 probes in male-specific region of chromosome-Y from genotyping array. We found that the PAHs exposure levels were linearly associated with mLOY. A 10-fold increase in urinary 1-hydroxynaphthalene (1-OHNa), 1-hydroxyphenanthrene (1-OHPh), 2-OHPh, 1-hydroxypyrene (1-OHP), ΣOH-PAHs, and plasma BPDE-Alb adducts could generate 0.0111, 0.0085, 0.0069, 0.0103, 0.0134, and 0.0152 decrease in mLRR-Y, respectively. Additionally, mLOY accelerated with age, smoking pack-years, and TCL1A rs1122138-C allele, and we observed the most severe mLOY among subjects carrying more than 3 of the above risk factors. Our results revealed the linear dose-effect associations between PAHs exposure and mLOY. Elder male smokers carrying rs1122138CC genotype were the most susceptible subpopulations to mLOY, who should be given protections for PAHs exposure induced chromosome-Y aberration.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31807838

RESUMO

Glycyrrhizic acid (GA) is one of the main active components in licorice and has often been reported to have cardioprotective effects. However, the underlying cellular mechanisms remain unclear. The aim of this study is to verify the protective effects of GA against isoproterenol (ISO)-induced myocardial ischemia injury in rats. Another aim is to explore the cellular mechanisms based on the L-type Ca2+ channel, myocardial cell contraction, and intracellular Ca2+ ([Ca2+]i) transient. The results show that GA reduced the ST segment elevation, decreased the heart rate, prevented ISO-induced QT-interval shortening, improved heart morphology, and decreased the activity of CK and LDH. GA blocked ICa-L in a dose-dependent manner. The concentration for 50% of the maximal effect (EC50) of GA was 145.54 µg/mL, and the maximal inhibition was 47.43 ± 0.75% at 1000 µg/mL. However, GA did not affect the dynamical properties of the Ca2+ channel. GA reversibly reduced the amplitude of cell contraction in a dose-dependent manner and slowed down its deflection and recovery, as well as the [Ca2+]i transient. The data demonstrate that GA inhibits L-type Ca2+ channels, decreases the [Ca2+]i transient, and shows a negative cardiac inotropic effect in the ventricular myocardial cells of adult rats. It also protects the myocardia from ischemia injury induced by ISO.

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