Generation of induced pluripotent stem cells (iPSCs) from somatic cells by defined factors is a mechanism-unknown, yet extremely time-consuming process. Inefficient reprogramming leads to prolonged periods of in vitro iPSC selection, resulting in subtle genetic and epigenetic abnormalities. To facilitate pluripotent reprogramming, we have identified the thyroid hormone triiodothyronine (T3) as an endogenous factor that can enhance reprogramming of human dermal fibroblasts (HDF) and umbilical cord mesenchymal stem cells (UCMSC). This potentiation of iPSC induction is associated with metabolic remodeling activity, including up-regulation of key glycolytic genes, an increase in cell proliferation, and the induction of mesenchymal-epithelial transition (MET). We further identify the activation of the PI3K/AKT signal pathway by T3 as an underlying mechanism for the enhanced conversion to cell pluripotency in this model. These studies demonstrate that T3 enhances metabolic remodeling of donor cells in potentiating cell reprogramming.
In a pre-specified subgroup analysis of a 12-week randomized multicenter study, we investigated effects of valsartan/amlodipine 80/5 mg single-pill combination (n = 75) and nifedipine GITS 30 mg (n = 75) on ambulatory blood pressure (BP) and arterial stiffness assessed by brachial-ankle pulse wave velocity (PWV) in patients with un-
Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. May Measurement Month (MMM) is a global initiative aimed at raising awareness of high BP and to act as a temporary solution to the lack of screening programmes worldwide. In China, several hypertension screening programmes are undertaken in the elderly in the community and in youths at university entrance and graduation. However, most people, especially the middle-aged working population, do not often have their BP measured. The current awareness (46.9%), treatment (40.7%), and control rates (15.3%) of hypertension remain low, while the proportion of screenees with hypertension is high in adult Chinese (23.2%). An opportunistic cross-sectional survey of volunteers aged ≥18 years was carried out in May 2017. Blood pressure measurement, the definition of hypertension and statistical analysis followed the standard MMM protocol. About 125 236 individuals were screened. After multiple imputation, with 124 623 as denominator, 32 089 (25.7%) had hypertension. Of the 103 981 individuals not on antihypertensive medication, 11 447 (11.0%) were hypertensive. Of the 20 547 individuals on antihypertensive medication, 7392 (36.0%) had uncontrolled BP (≥140/90 mmHg). An opportunistic screening may effectively identify those with high BP regardless of the use of antihypertensive medication and shows similar information on BP as a survey in a randomly selected population sample.
In an 8-week randomized trial of patients with mild or moderate hypertension, the authors investigated the efficacy and tolerability of initial high (5.0 mg/d) vs low (2.5 mg/d) doses of S-(-)-amlodipine (equivalent to 5 and 10 mg of racemic amlodipine, respectively). In the S-(-)-amlodipine 2.5-mg group (n=263), 24-hour ambulatory systolic/diastolic blood pressure (±standard deviation) decreased from 131.5± 15.0/82.1±10.7 mm Hg at baseline to 126.0±13.5/78.5±9.5 mm Hg at 8 weeks of follow-up by a least square mean (±standard error) change of 6.0±0.6/3.8±0.4 mm Hg.In the S-(-)-amlodipine 5-mg group (n=260), the corresponding changes were from 133.6±13.7/83.1±9.9 mm Hg to 125.0±12.0/78.2±8.9 mm Hg by 8.1±0.6/4.7±0.4 mm Hg, respectively. The between-group differences in changes in 24-hour systolic/diastolic blood pressure were 2.1/0.9 (P=.02/.17) mm Hg. Similar trends were observed for daytime and nighttime ambulatory and clinic blood pressure. The incidence rate was similar for all adverse events. An initial high dose of S-(-)-amlodipine improved ambulatory blood pressure control with similar tolerability as an initial low dose in hypertension.
We investigated the prevalence, awareness, treatment, and control of hypertension in a large opportunistic screening study in China. Our study participants had to be ≥18 years of age and had ideally not taken blood pressure (BP) for ≥1 year. BP was measured three times consecutively in the sitting position with a 1-minute interval, using a validated electronic BP monitor or mercury sphygmomanometer. Trained volunteer investigators administered a questionnaire to collect information on medical history, lifestyle, and use of medications. The 364 000 participants (52.6% women, and mean age 53.4 years) had a mean systolic/diastolic BP of 124.2/76.4 mm Hg. The proportion of hypertension was 24.7%. In all hypertensive subjects (n = 89 925), the awareness, treatment, and control rates of hypertension were 60.1%, 42.5%, and 25.4%, respectively. In multiple stepwise logistic regression analyses, the odds for unawareness vs awareness of hypertension was higher in men and lower with age advancing, current smoking, and the presence of diabetes mellitus, coronary heart disease, and stroke or transient ischemic attack (P < .0001). The odds for uncontrolled vs controlled hypertension was higher with age advancing and current smoking, and lower with the presence of diabetes mellitus and coronary heart disease (P ≤ .03) in 38 207 treated hypertensive patients, and it was also higher with the use of antihypertensive monotherapy (odds ratio 1.13, P = .0003) in 19 523 treated hypertensive patients with specific antihypertensive drugs. Our study identified several factors as barriers to BP control in China, such as male gender, younger age, current smoking, and the under-use of combination therapy. | INTRODUC TI ONAccording to the most recent China nationwide hypertension survey in 2012-2015, the crude prevalence of hypertension was 27.9%, and the awareness, treatment and control rates of hypertension were 46.9%, 40.7%, and 15.3%, respectively. 1 If this survey would be compared with the previous one in 2002, 2 the prevalence was substantially increased by an absolute percentage of 9.1% from 18.8%,
OBJECTIVE Atrial fibrillation (AF) and hypertension are prevalent chronic disease conditions in the elderly population. In the present cross-sectional study, we investigated the association between blood pressure (BP) and AF in an elderly Chinese population. METHOD Our elderly (≥65 years) subjects were residents recruited from 6 communities in Shanghai from 2006 to 2017. Atrial fibrillation was systematically screened by rest 12-lead electrocardiogram (ECG) or by a handheld single-lead ECG. BP status was defined according to the European hypertension guidelines as optimal, normal, or high-normal BP, and stage 1, 2, or 3 hypertension. RESULT In the 6,966 participants (women 56.0%, mean age: 72.3 years), the prevalence of AF was 3.3%, and the prevalence of hypertension was 58.7% (83.7% treated). In all participants, the association with prevalent AF was negative for systolic BP (odds ratio [OR] per 10-mm Hg increase 0.79, 95% confidence interval [CI]: 0.71–0.88, P < 0.0001) but positive for diastolic BP (OR per 5-mm Hg increase 1.11, 95% CI: 1.02–1.22, P = 0.02). In untreated participants (n = 3,544), the association with prevalent AF was U-shaped for both systolic and diastolic BP, with the nadir at high-normal BP and a significantly higher risk of prevalent AF in optimal systolic BP (OR: 3.11, 95% CI: 1.65–5.85, P = 0.004) and stage 2 or 3 diastolic hypertension relative to the nadir (OR: 8.04, 95% CI: 2.28–28.3, P = 0.001). CONCLUSION In the elderly population, BP shows a complicated relationship with prevalent AF, with high-normal BP at the lowest risk and optimal systolic BP and stage 2 or 3 diastolic hypertension at increased risks.
Mesenchymal stromal cells (MSCs) show potential for treating preclinical models of newborn bronchopulmonary dysplasia (BPD), but studies of their therapeutic effectiveness have had mixed results, in part due to the use of different media supplements for MSCs expansion in vitro. The current study sought to identify an optimal culture supplement of umbilical cord-derived MSCs (UC-MSCs) for BPD therapy. In this study, we found that UC-MSCs cultured with human platelet lysate (hPL-UCMSCs) were maintained a small size from Passage 1 (P1) to P10, while UC-MSCs cultured with fetal bovine serum (FBS-UCMSCs) became wide and flat. Furthermore, hPL was associated with lower levels of senescence in UC-MSCs during in vitro expansion compared with FBS, as indicated by the results of β-galactosidase staining and measures of senescence-related genes (CDKN2A, CDKN1A, and mTOR). In addition, hPL enhanced the proliferation and cell viability of the UC-MSCs and reduced their doubling time in vitro. Compared with FBS-UCMSCs, hPL-UCMSCs have a greater potential to differentiate into osteocytes and chondrocytes. Moreover, using hPL resulted in greater expression of Nestin and specific paracrine factors (VEGF, TGF-β1, FGF2, IL-8, and IL-6) in UC-MSCs compared to using FBS. Critically, we also found that hPL-UCMSCs are more effective than FBS-UCMSCs for the treatment of BPD in a rat model, with hPL leading to improvements in survival rate, lung architecture and fibrosis, and lung capillary density. Finally, qPCR of rat lung mRNA demonstrated that hPL-UCMSCs had lower expression levels of inflammatory factors (TNF-α and IL-1β) and a key chemokine (MCP-1) at postnatal day 10, and there was significant reduction of CD68+ macrophages in lung tissue after hPL-UCMSCs transplantation. Altogether, our findings suggest that hPL is an optimal culture supplement for UC-MSCs expansion in vitro, and that hPL-UCMSCs promote lung repair in rat BPD disease.
Background: Multiple piezoelectric pressure mechanotransducers topologized into an array might improve efficiency and accuracy in collecting arterial pressure waveforms for measurement of pulse wave velocity (PWV). Objective: In the present study, we validated a piezoelectric sensor array-based prototype (Philips) against the validated and clinically widely used Complior device (Alam Medical). Methods: We recruited 33 subjects with a wide distribution of PWV. For the validation, PWV was measured sequentially with the Complior device (four times) and the Philips prototype (three times). With the 99 paired PWV values, we investigated the agreement between the Philips prototype and the Complior device using Pearson correlation analysis and Bland-Altman plot. We also performed analysis on the determinants and reproducibility of PWV measured with both devices. Results: The correlation coefficient for PWV measured with the two devices was 0.92 (p < 0.0001). Compared with the Complior device, the Philips prototype slightly overestimated PWV by 0.24 (± 2 standard deviations, ± 1.91) m/s, especially when PWV was high. The correlation coefficient between the difference and the average of the Philips and Complior measurements was 0.21 (p = 0.035). Nonetheless, they had similar determinants. Age, mean arterial pressure, and sex altogether explained 81.6 and 83.9% of the variance of PWV values measured with the Philips prototype and Complior device, respectively. When the two extremes of the three PWV values measured with the Philips prototype and the Complior device were investigated, the coefficients of variation were 8.26 and 3.26%, respectively. Conclusions: Compared with the Complior device, the Philips prototype had similar accuracy, determinants, and reproducibility in measuring PWV.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.