Abstract
Regulation of fatty acid uptake, lipid production and storage, and metabolism of lipid droplets (LDs), is closely related to lipid homeostasis, adipocyte hypertrophy and obesity. We report ...here that stomatin, a major constituent of lipid raft, participates in adipogenesis and adipocyte maturation by modulating related signaling pathways. In adipocyte-like cells, increased stomatin promotes LD growth or enlargements by facilitating LD-LD fusion. It also promotes fatty acid uptake from extracellular environment by recruiting effector molecules, such as FAT/CD36 translocase, to lipid rafts to promote internalization of fatty acids. Stomatin transgenic mice fed with high-fat diet exhibit obesity, insulin resistance and hepatic impairments; however, such phenotypes are not seen in transgenic animals fed with regular diet. Inhibitions of stomatin by gene knockdown or OB-1 inhibit adipogenic differentiation and LD growth through downregulation of PPAR
γ
pathway. Effects of stomatin on PPAR
γ
involves ERK signaling; however, an alternate pathway may also exist.
Most studies support that saturated fatty acid replacement with polyunsaturated fatty acids (PUFAs) may reduce the risk of cardiovascular diseases (CVDs) and put emphasis on the effects of N-3 PUFAs. ...The reported relationships between N-6 PUFAs and CVD risks vary. We aimed to examine the associations between N-6 PUFA concentrations and CVD risks. In this community-based prospective cohort study on CVD-free patients at baseline (N = 1835, age: 60.6 ± 10.5 years, women: 44.5%), we measured the fatty acid concentrations in the blood using gas chromatography. Four hundred twenty-four participants developed CVDs during follow up. The total N-6 PUFA concentration was inversely associated with the CVD risk, with a 48% lower risk in the highest N-6 PUFA concentration quartile (hazard ratio = 0.52; P for trend <0.001). The estimated population attributable risk of N-6 PUFAs indicated that approximately 20.7% of CVD events would have been prevented if the plasma N-6 PUFA concentration had been higher than the median value. The total N-6 PUFA concentration presented the highest net reclassification improvement (NRI = 7.2%, P = 0.03) for predicting incident CVD. Further studies on N-6 PUFAs, diet habits, and their relationships with healthcare are warranted.
Light–matter interactions are often considered to be mediated by the electric component of light only, neglecting the magnetic contribution. However, the electromagnetic energy density is equally ...distributed between both parts of the optical fields. Within this scope, we experimentally demonstrate here, in excellent agreement with numerical simulations, that plasmonic nanostructures can selectively manipulate and tune the magnetic versus electric emission of luminescent nanocrystals. In particular, we show selective enhancement or decay of magnetic and electric emission from trivalent europium-doped nanoparticles in the vicinity of plasmonic nanocavities, designed to efficiently couple to either the electric or magnetic emission of the quantum emitter. Specifically, by precisely controlling the spatial position of the emitter with respect to our plasmonic nanostructures, by means of a near-field optical microscope, we record local distributions of both magnetic and electric radiative local densities of states (LDOS) with nanoscale precision. The distribution of the radiative LDOS reveals the modification of both the magnetic and electric optical quantum environments induced by the presence of the metallic nanocavities. This manipulation and enhancement of magnetic light–matter interaction by means of plasmonic nanostructures opens up new possibilities for the research fields of optoelectronics, chiral optics, nonlinear and nano-optics, spintronics, and metamaterials, among others.
Statins possess neuroprotective effects. However, real-world evidence supporting their utility in post-stroke epilepsy (PSE) prevention is limited.
The association between statin use, including ...timing of prescribing (pre-stroke vs post-stroke), type (lipophilicity, intensity of therapy) and dose intensity, and risk of developing PSE were investigated by studying Taiwanese health claims (2003-2013).
Patients with new-onset ischaemic stroke were identified. The main outcome was a diagnosis of epilepsy after ischaemic stroke. According to pre-stroke statin use, groups of current users, former users, and non-users were compared using ANOVA. An extended Cox regression model was utilized to estimate the hazard ratio (HR) of PSE, with post-stroke statin use and certain comedications as time-dependent variables. Serial sensitivity analyses were performed to ensure study robustness.
Of the 20,858 ischaemic stroke patients, 954 (4.6%) developed PSE. Post-stroke statin use (adjusted HR (aHR) 0.55; 95% confidence interval 0.46-0.67, p < 0.001), but not pre-stroke statin use was associated with a significantly reduced risk of developing PSE. A dose-response correlation was also observed between PSE risk reduction and quartiles of the statin cumulative defined daily dose (cDDD) (aHR 0.84, 0.67, 0.53, and 0.50 for the lowest, second, third, and highest quartiles of cDDD, respectively). Risk predictors and protectors against PSE were also characterized.
The post-stroke use of statins after ischaemic stroke was associated with PSE risk reduction in a cDDD-dependent manner. Further clinical studies on the potential applications of statins for PSE prophylaxis, particularly among at-risk patients, are warranted.
Approximately 25% of the population in Taiwan has hypertension, and the rate has increased over time. Although age‐standardized cardiovascular mortality has decreased over the last 25 years, the ...annual stroke incidence has increased, and national health insurance reimbursement for cardiovascular disease (CVD) has grown by 22% over the last 10 years. Automatic oscillometric sphygmomanometer devices are increasingly available and affordable in Taiwan, making this the main method of out‐of‐office blood pressure (BP) measurement. Furthermore, home blood pressure monitoring (HBPM), along with shared informed decision making, could be beneficial in driving changes in health behavior and hypertension management. The 2015 Guidelines of the Taiwan Society of Cardiology and the Taiwan Hypertension Society for the Management of Hypertension recognize that home BP is a stronger predictor of CVD than office BP. Therefore, HBPM is recommended and implementation instructions provided. However, a home BP target that corresponds to the office BP used in the majority of clinical studies has yet to be clearly defined. Care for hypertension in Taiwan takes place more often in the hospital versus primary care setting. Combination therapy, often fixed drug combinations, is needed in 60% of patients to achieve BP control. Calcium channel blockers are the most commonly prescribed agents, followed by angiotensin receptor blockers. Overall, there is still substantial room for improvement in the awareness, treatment, and control rate of hypertension in Taiwan. HBPM has a central diagnostic and prognostic role in the management of hypertension.
Fibromyalgia (FM) is a stress-related chronic pain disorder with common cognitive complaints. This study characterized cognitive dysfunction in patients with FM and explored whether these changes are ...linked to altered cortisol levels. Consecutive 44 patients with FM and 48 healthy controls were enrolled for the assessments of subjective and objective cognitive functions and diurnal levels of salivary cortisol (sampled at awakening, 30 min after awakening, 3 pm, and bedtime). All measurements were compared between the groups and evaluated for clinical correlation. The FM group had more subjective cognitive complaints and performed poorer in objective cognitive testing in memory (delayed recall in Chinese Version Verbal Learning Test and Taylor Complex Figure Test), language (Boston Naming Test), and executive domains (Wisconsin Card Sorting Test) after adjustments for education. The diurnal cortisol levels of patients with FM tended to be lower, especially at 30 min after awakening and bedtime. Moreover, moderate positive correlations existed between the Chinese Version Verbal Learning Test, Boston Naming Test and the morning cortisol levels within the FM group. We suggested the altered cognitive function in FM may be linked to stress maladaptation. Future studies are warranted to elucidate whether stress management improves cognitive performance in patients with FM.
Remuscularization of the mammalian heart can be achieved after cell transplantation of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs). However, several hurdles remain before ...implementation into clinical practice. Poor survival of the implanted cells is related to insufficient vascularization, and the potential for fatal arrhythmogenesis is associated with the fetal cell-like nature of immature CMs.
We generated 3 lines of hiPSC-derived endothelial cells (ECs) and hiPSC-CMs from 3 independent donors and tested hiPSC-CM sarcomeric length, gap junction protein, and calcium-handling ability in coculture with ECs. Next, we examined the therapeutic effect of the cotransplantation of hiPSC-ECs and hiPSC-CMs in nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice undergoing myocardial infarction (n≥4). Cardiac function was assessed by echocardiography, whereas arrhythmic events were recorded using 3-lead ECGs. We further used healthy non-human primates (n=4) with cell injection to study the cell engraftment, maturation, and integration of transplanted hiPSC-CMs, alone or along with hiPSC-ECs, by histological analysis. Last, we tested the cell therapy in ischemic reperfusion injury in non-human primates (n=4, 3, and 4 for EC+CM, CM, and control, respectively). Cardiac function was evaluated by echocardiography and cardiac MRI, whereas arrhythmic events were monitored by telemetric ECG recorders. Cell engraftment, angiogenesis, and host-graft integration of human grafts were also investigated.
We demonstrated that human iPSC-ECs promote the maturity and function of hiPSC-CMs in vitro and in vivo. When cocultured with ECs, CMs showed more mature phenotypes in cellular structure and function. In the mouse model, cotransplantation augmented the EC-accompanied vascularization in the grafts, promoted the maturity of CMs at the infarct area, and improved cardiac function after myocardial infarction. Furthermore, in non-human primates, transplantation of ECs and CMs significantly enhanced graft size and vasculature and improved cardiac function after ischemic reperfusion.
These results demonstrate the synergistic effect of combining iPSC-derived ECs and CMs for therapy in the postmyocardial infarction heart, enabling a promising strategy toward clinical translation.
Glioblastoma (GBM) is the most common primary brain malignancy in adults. Despite multimodal treatment that involves maximal safe resection, concurrent chemoradiotherapy, and tumour treatment for ...supratentorial lesions, the prognosis remains poor. The current median overall survival is only <2 years, and the 5-year survival is only 7.2%. Thioredoxin domain-containing protein 11 (TXNDC11), also known as EF-hand binding protein 1, was reported as an endoplasmic reticulum stress-induced protein. The present study aimed to elucidate the prognostic role of TXNDC11 in GBM. We evaluated the clinical parameters and TXNDC11 scores in gliomas from hospitals. Additionally, proliferation, invasion, migration assays, apoptosis, and temozolomide (TMZ)-sensitivity assays of GBM cells were conducted to evaluate the effects of short interfering RNA (siRNA) on these processes. In addition, these cells were subjected to Western blotting to detect the expression levels of N-cadherin, E-cadherin, and Cyclin D1. High levels of TXNDC11 protein expression were significantly associated with World Health Organization (WHO) high-grade tumour classification and poor prognosis. Multivariate analysis revealed that in addition to the WHO grade, TXNDC11 protein expression was also an independent prognostic factor of glioma. In addition, TXNDC11 silencing inhibited proliferation, migration, and invasion and led to apoptosis of GBM cells. However, over-expression of TXNDC11 enhanced proliferation, migration, and invasion. Further, TXNDC11 knockdown downregulated N-cadherin and cyclin D1 expression and upregulated E-cadherin expression in GBM cells. Knock-in TXNDC11 return these. Finally, in vivo, orthotopic xenotransplantation of TXNDC11-silenced GBM cells into nude rats promoted slower tumour growth and prolonged survival time. TXNDC11 is a potential oncogene in GBMs and may be an emerging therapeutic target.
The development of microarrays permits us to monitor transcriptomes on a genome-wide scale. To validate microarray measurements, quantitative-real time-reverse transcription PCR (Q-RT-PCR) is one of ...the most robust and commonly used approaches. The new challenge in gene quantification analysis is how to explicitly incorporate statistical estimation in such studies. In the realm of statistical analysis, the various available methods of the probe level normalization for microarray analysis may result in distinctly different target selections and variation in the scores for the correlation between microarray and Q-RT-PCR. Moreover, it remains a major challenge to identify a proper internal control for Q-RT-PCR when confirming microarray measurements.
Sixty-six Affymetrix microarray slides using lung adenocarcinoma tissue RNAs were analyzed by a statistical re-sampling method in order to detect genes with minimal variation in gene expression. By this approach, we identified DDX5 as a novel internal control for Q-RT-PCR. Twenty-three genes, which were differentially expressed between adjacent normal and tumor samples, were selected and analyzed using 24 paired lung adenocarcinoma samples by Q-RT-PCR using two internal controls, DDX5 and GAPDH. The percentage correlation between Q-RT-PCR and microarray were 70% and 48% by using DDX5 and GAPDH as internal controls, respectively.
Together, these quantification strategies for Q-RT-PCR data processing procedure, which focused on minimal variation, ought to significantly facilitate internal control evaluation and selection for Q-RT-PCR when corroborating microarray data.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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