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Trauma‐hemorrhagic shock (THS) is a medical emergency that is encountered by physicians in the emergency department. Chuan Xiong is a traditional Chinese medicine and ligustrazine is a natural compound from it. Ligustrazine improves coronary blood flow and reduces cardiac ischemia in animals through Ca2+ and ATP‐dependent vascular relaxation. It also decreases the platelets' bioactivity and reduces reactive oxygen species formation. We hypothesized that ligustrazine could protect liver by decreasing the inflammation response, protein production, and apoptosis in THS rats. Ligustrazine at doses of 100 and 1000 μg/mL was administrated in Kupffer cells isolated from THS rats. The protein expressions were detected via western blot. The THS showed increased inflammation response proteins, mitochondria‐dependent apoptosis proteins, and had a compensation effect on the Akt pathway. After ligustrazine treatment, the hemorrhagic shock Kupffer cells decreased inflammatory response and mitochondria‐dependent apoptosis and promoted a more compensative effect of the Akt pathway. It suggests ligustrazine reduces inflammation response and mitochondria‐dependent apoptosis induced by THS in liver Kupffer cells and promotes more survival effects by elevating the Akt pathway. These findings demonstrate the beneficial effects of ligustrazine against THS‐induced hepatic injury, and ligustrazine could be a potential medication to treat the liver injury caused by THS. [ABSTRACT FROM AUTHOR]

Aim: To determine the risk patterns associated with transient hearing impairment (THI) and permanent hearing loss (PHL) of infants born very preterm who failed hearing screenings. Method: We enrolled 646 infants (347 males, 299 females) born at no more than 30 weeks' gestation between 2006 and 2020 who received auditory brainstem response screening at term‐equivalent age. Audiological examinations of infants who failed the screening revealed THI, when hearing normalized, or PHL, defined as a persistent unilateral or bilateral hearing threshold above 20 dB. Principal component analysis (PCA) was used to characterize risk patterns. Results: Among the 646 infants, 584 (90.4%) had normal hearing, 42 (6.5%) had THI, and 20 (3.1%) had PHL. Compared with the group with normal hearing, the THI and PHL groups had significantly higher rates of neurodevelopmental impairment at 24 months corrected age. PCA of risk patterns showed the THI group and especially the PHL group had more severe haemodynamic and respiratory instability. Moreover, severe intraventricular haemorrhage (IVH) was also a risk for PHL. Propensity score matching revealed an association of haemodynamic and respiratory instability with PHL. Interpretation: In infants born preterm, the severity and duration of haemodynamic and respiratory instability are risk patterns for both THI and PHL; severe IVH is an additional risk for PHL. What this paper adds: Neurodevelopmental delay was more common in infants born preterm who failed hearing screening.Principal component analysis revealed the risk patterns associated with hearing impairment.Haemodynamic–respiratory instability was associated with transient and permanent hearing impairment outcomes.Severe haemodynamic–respiratory instability and intraventricular haemorrhage was associated with permanent hearing loss. [ABSTRACT FROM AUTHOR]

In this paper, we propose Bayesian analysis methods dealing with longitudinal data involving repeated binary outcomes on subjects with dropouts. The proposed Bayesian methods implement probit models with random effects to capture heterogeneity and hypersphere decomposition to model the correlation matrix for serial correlation of repeated responses. We investigate the model robustness against misspecifications of the probit models along with techniques to handle missing data. The parameters of the proposed models are estimated by implementing an Markov chain Monte Carlo (MCMC) algorithm, and simulations were performed to provide a comparison with other models and validate the choice of prior distributions. The simulations show that when suitable correlation structures are specified, the proposed approach improves estimation of the regression parameters in terms of the mean percent relative error and the mean squared error. Finally, two real data examples are provided to illustrate the proposed approach. [ABSTRACT FROM AUTHOR]

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The class of nature‐inspired metaheuristic algorithms is increasingly used to tackle all kinds of optimization problems across disciplines. It also plays an important component in artificial intelligence and machine learning. Members in this class are general purpose optimization tools that virtually require no assumptions for them to be applicable. There are many such algorithms, and to fix ideas, we review one of its exemplary members called particle swarm optimization (PSO). We discuss the algorithm, its recent applications to find different types of efficient experimental designs, and provide resources, where codes for PSO and other metaheuristic algorithms and tutorials with examples are available. This article is categorized under:Algorithms and Computational Methods > Genetic Algorithms and Evolutionary Computing [ABSTRACT FROM AUTHOR]

Hypertension is a common chronic cardiovascular disease reported among both men and women. Hypertension in males affects the testis and reproduction function; however, the pathogenesis is poorly understood. Rapamycin has been reported to have a variety of beneficial pharmacological effects; however, high‐doses rapamycin does have side effects such as immunosuppression. The present study investigates whether low‐dose rapamycin can reduce the damage caused by hypertension to the testis of spontaneously hypertensive rats (SHRs) and further examines molecular mechanism of low‐dose rapamycin in preventing testicular toxicity induced by angiotensin II (Ang II). Low rapamycin dose restores the testicle size, histological alterations, 3β‐hydroxysteroid dehydrogenase (3β‐HSD) expression, and prevents apoptosis in SHR rats. Ang II downregulates angiotensin‐converting enzyme‐2 (ACE2) expression through AT1R, p‐ERK, and MAS receptor in LC‐540 Leydig cells in a dose‐dependent manner. Low doses of rapamycin effectively upregulate steroidogenic enzymes, steroidogenic acute regulatory protein and 3β‐HSD expression in Leydig cells. Rapamycin upregulates ACE2 expression through p‐PKAc and p‐PI3k in Ang II‐treated cells. Further, rapamycin curbs mitochondrial superoxide generation and depleted mitochondrial membrane potential induced by Ang II through activation of Nrf2‐mediated Gpx4 and superoxide dismutase 2 expression. Our results revealed the involvement of ACE2, AT1R, AT2R, PKAc, and oxidative stress in Ang‐II‐induced testicular toxicity, suggesting low‐dose rapamycin could be a potential therapeutic candidate to attenuate testicular toxicity. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy is a serious chronic complication affecting at least 25% of diabetic patients. Hyperglycemia associated advanced glycation end‐products (AGEs) increase tubular epithelial‐myofibroblast transdifferentiation (TEMT) and extracellular matrix synthesis and thereby causes renal fibrosis. The chalcone isoliquiritigenin, found in many herbs of Glycyrrhiza family, is known for potential health‐promoting effects. However, their effects on AGE‐associated renal proximal tubular fibrosis are not known yet. In this study, the effect of isoliquiritigenin on AGE‐induced renal proximal tubular fibrosis was determined in cultured HK‐2 cell line. The results show that 200 μg/mL of AGE‐induced TEMT and the formed myofibroblasts synthesized collagen to increase extracellular matrix formation thereby lead to renal tubular fibrosis. However, treatment with 200 nM of isoliquiritigenin considerably inhibited the TEMT and suppressed the TGFβ/STAT3 mechanism to inhibit collagen secretion. Therefore, isoliquiritigenin effectively suppressed AGE‐induced renal tubular fibrosis. [ABSTRACT FROM AUTHOR]

Diabetic neuropathy is a common complication of diabetes mellitus, posing a challenge in treatment. Previous studies have indicated the protective role of mesenchymal stem cells against several disorders. Although they can repair nerve injury, their key limitation is that they reduce viability under stress conditions. We recently observed that overactivation of the carboxyl terminus of heat shock protein 70 (Hsp70) interacting protein (CHIP) considerably rescued cell viability under hyperglycemic stress and played an essential role in promoting the beneficial effects of Wharton's jelly‐derived mesenchymal stem cells (WJMSCs). Thus, the present study was designed to unveil the protective effects of CHIP‐overexpressing WJMSCs against neurodegeneration using in vivo animal model based study. In this study, western blotting observed that CHIP‐overexpressing WJMSCs could rescue nerve damage observed in streptozotocin‐induced diabetic rats by activating the AMPKα/AKT and PGC1α/SIRT1 signaling pathway. In contrast, these signaling pathways were downregulated upon silencing CHIP. Furthermore, CHIP‐overexpressing WJMSCs inhibited inflammation induced in the brains of diabetic rats by suppressing the NF‐κB, its downstream iNOS and cytokines signaling nexus and enhancing the antioxidant enzyme system. Moreover, TUNEL assay demonstrated that CHIP carrying WJMSCs suppressed the apoptotic cell death induced in STZ‐induced diabetic group. Collectively, our findings suggests that CHIP‐overexpressing WJMSCs might exerts beneficial effects, which may be considered as a therapeutic strategy against diabetic neuropathy complications. [ABSTRACT FROM AUTHOR]

Some clinical studies have indicated the patients with Alzheimer's disease (AD) display an increased risk of cardiovascular disease (CVD). Here, to examine the relationship between AD and CVDs, we investigated the changes in heart function in triple‐transgenic late‐stage AD model mice (3× Tg‐AD; APPSwe, PS1M146V, and tauP301L). We fed the AD mice folic acid (FA) or folinic acid (FN) and analyzed the protective effects of the compounds on the heart; specifically, 20‐month‐old triple‐transgenic AD mice, weighing 34–55 g, were randomly allocated into three groups—the AD, AD + FA, and AD + FN groups—and subject to gastric feeding with FA or FN once daily at 12 mg/kg body weight (BW) for 3 months. Mouse BWs were assessed throughout the trial, at the end of which the animals were sacrificed using carbon dioxide suffocation. We found that BW, whole‐heart weight, and left‐ventricle weight were reduced in the AD + FA and AD + FN groups as compared with the measurements in the AD group. Furthermore, western blotting of excised heart tissue revealed that the levels of the hypertrophy‐related protein markers phospho(p)‐p38 and p‐c‐Jun were markedly decreased in the AD + FA group, whereas p‐GATA4, and ANP were strongly reduced in the AD + FN group. Moreover, the fibrosis‐related proteins uPA, MMP‐2, MEK1/2 and SP‐1 were decreased in the heart in both AD + FN group. In summary, our results indicate that FA and FN can exert anti‐cardiac hypertrophy and fibrosis effects to protect the heart in aged triple‐transgenic AD model mice, particular in FN. [ABSTRACT FROM AUTHOR]

In this article, we present a Bayesian framework for multivariate longitudinal data analysis with a focus on selection of important elements in the generalized autoregressive matrix. An efficient Gibbs sampling algorithm was developed for the proposed model and its implementation in a comprehensive R package called MLModelSelection is available on the comprehensive R archive network. The performance of the proposed approach was studied via a comprehensive simulation study. The effectiveness of the methodology was illustrated using a nonalcoholic fatty liver disease dataset to study correlations in multiple responses over time to explain the joint variability of lung functions and body mass index. Supplementary materials for this article, including a standardized description of the materials needed to reproduce the work, are available as an online supplement. [ABSTRACT FROM AUTHOR]

Oxidative stress‐induced brain cell damage is a crucial factor in the pathogenesis of reactive oxygen species (ROS)‐associated neurological diseases. Further, studies show that astrocytes are an important immunocompetent cell in the brain and play a potentially significant role in various neurological diseases. Therefore, elimination of ROS overproduction might be a potential strategy for preventing and treating neurological diseases. Accumulating evidence indicates that calycosin, a main active ingredient in the Chinese herbal medicine Huangqi (Radix Astragali Mongolici), is a potential therapeutic candidate with anti‐inflammation and/or anticancer effects. Here, we investigated the protective effect of calycosin in brain astrocytes by mimicking in vitro oxidative stress using H2O2. The results revealed that H2O2 significantly induced ROS and inflammatory factor (tumor necrosis factor [TNF]‐α and interleukin [IL]‐1β) production, whereas post‐treatment with calycosin dramatically and concentration‐dependently suppressed H2O2‐induced damage by enhancing cell viability, repressing ROS and inflammatory factor production, and increasing superoxide dismutase (SOD) expression. Additionally, we found that calycosin facilitated nuclear factor erythroid 2‐related factor 2 (Nrf2) expression and promoted its nuclear translocation, thereby inducing the expression of antioxidant molecules (heme oxygenase [HO]‐1 and SOD) following H2O2 treatment. Moreover, calycosin did not attenuated H2O2‐induced astrocyte damage and ROS production in the presence of the ML385 (a Nrf2‐specific inhibitor) and following Nrf2 silencing. Furthermore, calycosin failed to increase Akt phosphorylation and mitigate H2O2‐induced astrocyte damage in the presence of the LY294002 (a selective phosphatidylinositol 3‐kinase inhibitor), indicating that calycosin‐mediated regulation of oxidative‐stress homeostasis involved Akt/Nrf2/HO‐1 signaling. These findings demonstrated that calycosin protects against oxidative injury in brain astrocytes by regulating oxidative stress through the AKT/Nrf2/HO‐1 signaling pathway. [ABSTRACT FROM AUTHOR]

The insulin‐like growth factor II receptor (IGF‐IIR) induces myocardial hypertrophy under various pathological conditions like diabetes and hypertension via G protein receptors like Gαq or Gαs. Increased expression of the ligand IGF II and IGF‐IIR induces pathological hypertrophy through downstream signaling mediators such as calcineurin, nuclear factor of activated T cells 3 and calcium‐calmodulin (CaM)‐dependent kinase II (CaMKII)‐histone deacetylase 4 (HDAC4). The dried stigma of Crocus sativus L. (saffron) has a long repute as a traditional medicine against various disorders. In the present study, we have investigated whether C. sativus extract (CSE) canameliorate Leu27IGF‐II triggered hypertrophy and have elucidated the underlying mechanism of protection. Additionally, the effects of oleic acid (OA), an activator of calcineurin and CaMKII was investigated thereof. The results demonstrate that CSE can ameliorate Leu27IGF‐II‐induced hypertrophy seemingly through regulation of calcineurin‐NFAT3 and CaMKII‐HDAC4 signaling cascade. [ABSTRACT FROM AUTHOR]

Naphthalimide derivatives have multiple biological activities, including antitumour and anti‐inflammatory activities. We previously synthesized several naphthalimide derivatives; of them, compound 5 was found to exert the strongest inhibitory effect on human DNA topoisomerase II activity. However, the effects of naphthalimide derivatives on platelet activation have not yet been investigated. Therefore, the mechanism underlying the antiplatelet activity of compound 5 was determined in this study. The data revealed that compound 5 (5–10 μM) inhibited collagen‐ and convulxin‐ but not thrombin‐ or U46619‐mediated platelet aggregation, suggesting that compound 5 is more sensitive to the inhibition of glycoprotein VI (GPVI) signalling. Indeed, compound 5 could inhibit the phosphorylation of signalling molecules downstream of GPVI, followed by the inhibition of calcium mobilization, granule release and GPIIb/IIIa activation. Moreover, compound 5 prevented pulmonary embolism and prolonged the occlusion time, but tended to prolong the bleeding time, indicating that it can prevent thrombus formation but may increase bleeding risk. This study is the first to demonstrate that the naphthalimide derivative compound 5 exerts antiplatelet and antithrombotic effects. Future studies should modify compound 5 to synthesize more potent and efficient antiplatelet agents while minimizing bleeding risk, which may offer a therapeutic potential for cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Epimedium, is used traditionally in Chinese medicine to treat infertility problems. In this study, we establish the cell model to elucidate the protective effect of epimedium against ES by analyzing the molecular relationship between mitochondrial dynamics and steroidogenesis and to explore the molecular mechanism focusing on mitochondria function relating to fertility. ES induced ROS accumulation in mitochondria and the epimedium treatment significantly reduced the ROS accumulation. Furthermore, mitochondria morphology was restored to elongated shape following epimedium treatment. Epimedium treatment promoted dynamin‐associated protein 1 (Drp1)‐mediated steroidogenesis pathway by upregulating PKA, CREB, Drp1, and StAR protein expression in response to ES exposure in Leydig cells. Moreover, it was also identified that, CREB plays an important role in epimedium activation in Drp1‐mediated steroidogenesis signaling pathway by increasing, phospho‐CREB expression in nucleus. Testosterone level is decreased in ES‐exposed cells; however, the testosterone level was increased after epimedium treatment. In conclusion, epimedium treatment improved mitochondria function in ES‐exposed Leydig cells and activated downstream Drp1‐dependent steroidogenesis by CREB mediated signaling pathway. [ABSTRACT FROM AUTHOR]

Habitual chewing of areca nut increases the risk of cardiovascular disease mortality, but less report demonstrate the toxic mechanism of areca nut on heart. To investigate toxicity of areca nut on cardiomyocytes, we induced the heart injury with arecoline to evaluate the acute damage of areca nut on heart. Different concentrations of are coline (lowdosage: 5 mg/kg/day and high dosage 50 mg/kg/day) were injected into Sprague‐Dawley rat via intra‐peritoneal method for 21 days to create negative effects of arecoline on cardiomyocyte. Themyocardial architecture of the rat heart was observed. The arecoline‐induced apoptotic proteins were analysed via western blotting. The myocardialarchitecture of heart was injured with arecoline and TUNEL stain was also shown are coline‐induced cardiac apoptosis. Arecoline promoted the protein expression of both Fas dependent snd mitochondrial dependent apoptosis. In summary, arecoline induces cardiac toxicity and apoptosis by inducing both death receptor and mitochondria‐dependent apoptotic pathways on heart. [ABSTRACT FROM AUTHOR]

Integrated photonics has shown extraordinary potential in optical computing. Various optical computing modules have been investigated, among which the digital comparator is a significant element for any arithmetic logic unit. In this study, an architecture of a wavelength‐division‐multiplexing‐based (WDM‐based) electronic–photonic digital comparator is proposed, which can perform high‐bit comparisons for fixed‐point or floating‐point binary inputs. A silicon photonics‐based 2‐bit comparator operating at 20 Gb s−1 at a 1.55 µm wavelength is experimentally demonstrated. A detailed performance analysis reveals that this architecture outperforms the current transistor‐based electronic comparators in terms of both computational speed and power efficiency. [ABSTRACT FROM AUTHOR]

Grouping selection arises naturally in many statistical modeling problems. Several group selection methods have been proposed in the last two decades. In this paper, we review the Bayesian group selection approaches for linear regression models. We start from the Bayesian indicator approach and then move to the Bayesian group LASSO methods. In addition, we also consider the Bayesian methods for the sparse group selection that can be treated as an extension of the group selection. Finally, we mention some extensions of Bayesian group selection for the generalized linear models and the multiple response models. This article is categorized under:Statistical and Graphical Methods of Data Analysis > Dimension ReductionStatistical and Graphical Methods of Data Analysis > Bayesian Methods and TheoryStatistical Models > Model Selection [ABSTRACT FROM AUTHOR]

In aging hypertensive conditions, deterioration of insulin‐like growth factor 1 receptor (IGF1R) cause a pathological impact on hypertensive hearts with an increased Ang II level. Recovering these adverse conditions through transplanted adipose‐derived stem cells is a challenging approach. Moreover, Danggui, a Traditional Chinese medicine (TCM), is used for the treatment of cardioprotective effects. In this study, to evaluate whether the combined effect of MSCs and TCM can recover the cardiac function in late‐stage hypertension rats. We observed that lower dose of Danggui crude extract treatment showed an increased level of cell viability with maintained stemness properties and growth rate in rat adipose‐derived stem cells (rADSCs). Further, we cocultured the H9c2 cells with rADSCs and the results revealed that Danggui‐treated MSCs enhanced the IGF1R expression and attenuated the hypertrophy in H9c2 cells against Ang II challenge by immunoblot and rhodamine‐phalloidin staining. In addition, Danggui crude extract was also quantified and characterized by HPLC and LC–MS analysis. Furthermore, the in vivo study was performed by considering 11 months old rats (n = 7). Importantly, the oral administration of Danggui crude extract with stem cells intravenous injection in SHR‐D‐ADSCs group showed a combination effect to augment the cardiac function through enhancement of ejection fraction, fractional shortening, contractility function in the late‐stage hypertension conditions. We have also observed a decreased apoptosis rate in the heart tissue of SHR‐D‐ADSCs group. Taken together, these results indicate that the combinatorial effects of Danggui crude extract and stem cell therapy enhanced cardiac function in late‐stage SHR rats. [ABSTRACT FROM AUTHOR]

Heart failure (HF) and cardiac hypertrophy is an unfavorable outcome of pathological cardiac remodeling and represents the most important contributing factor for HF and cardiac hypertrophy. Amygdalin (AMG) is a cyanogenic glycoside derived from bitter almonds. Accumulating evidences have highlighted their pharmacological potentials against various diseases. However, there is no report delineating the potential of AMG against angiotensin (Ang II) induced cardiac injuries. Thus, the present study was performed to explore whether AMG could ameliorate Ang II induced cardiomyopathies and thereby ascertain the underlying mechanisms thereof. To this end, H9c2 cells were treated with Ang II and thereafter treated with various concentration of AMG and finally the cardio‐protective effects of AMG were analyzed through Western blotting, immunofluorescence, and insilico analysis. Our results showed that the cardiomyocyte cell size, inflammatory markers and cytokines(pNF‐κB, TNF‐α, iNOS and COX‐2) were markedly increased following Ang II treatment; nevertheless, treatment with AMG led to considerable decrement in the Ang II induced enlargement of the cardiomyocytes, and attenuate the expression of hypertrophic markers(ANP, BNP and MHC‐7), inflammatory markers and cytokines. Additionally, oxidative stress related proteins (Nrf2, catalase, SOD‐2, and GPX‐4) were markedly increased following AMG treatment. Molecular docking reveals the interaction of AMG with Nrf2 possessing good binding affinity. Cumulatively, our study highlights the cardio‐protective role of AMG against Ang II induced cardiomyopathies, including oxidative stress and inflammation effects. The intriguing in vitro results warrants the need of further animal studies to truly ascertain their potentialities. [ABSTRACT FROM AUTHOR]

COVID-19 has caused a huge mayhem globally. Different economic freedom leads to different performances of a country's reaction to the pandemic. We study 164 countries and apply mathematical and statistical approaches to tackle the problem: whether economic freedom has a significant impact on the death of COVID-19. We devise a metric, some norms, and some orderings to construct an absolute reference and the actual relation via binary sequences. Then, we use the theoretical binary sequences to construct a probability distribution which linearises the strength of relation between economic freedom and death of COVID-19. Then, the actual relation from the data analysis provides an evidence to the hypothetical testing. Our analysis and model show that there is no significant relation between economic freedom and death of COVID-19. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is considered to be a serious clinical complication, which could cause significant liver dysfunction including fibrosis, cirrhosis, and cancer. Obesity could lead to NAFLD and contributes to liver disorder and related complicated liver diseases. Effect of exercise combined with alcalase treatment derived potato protein hydrolysate (APPH) on high‐fat diet (HFD)‐induced hepatic injury was investigated in senescence accelerated mouse‐prone 8 (SAMP8) mice in the present study. Mice were divided into six groups (n = 6): Group I‐Control, Group II‐HFD, Group III‐Exercise, Group IV‐HFD + APPH, Group V‐HFD + Exercise, and Group VI‐HFD + Exercise + APPH. Combined APPH treatment and exercise offer better cytoprotection in HFD‐induced histological changes than APPH treatment and exercise alone. Further, APPH and exercise activate the cell survival proteins PI3K/Akt and prevent FasL/FADD‐mediated apoptosis in HFD fed SAMP8 mouse. APPH with swimming exercise effectively modulate HFD‐induced liver damage and apoptosis in aged mice through activation of PI3K/Akt protein. Practical applications: Exercise training is proven to reduce the health problems associated with aging and obesity, however, intensity and duration of the exercise differs between individuals. We used integrated pharmacological and nonpharmacological approach as a therapeutic strategy for preventing HFD‐induced hepatic injury in aged subjects. [ABSTRACT FROM AUTHOR]

The origin and evolution of SARS-CoV-2 has been an important issue in tackling COVID-19. Research on these topics would enhance our knowledge of this virus and help us develop vaccines or predict its paths of mutations. There are many theoretical and clinical researches in this area. In this article, we devise a structural metric which directly measures the structural differences between any two nucleotide sequences. In order to explore the mechanisms of how the evolution works, we associate the nucleotide sequences of SARS-CoV-2 and its related families with the degrees of randomness. Since the distances between randomly generated nucleotide sequences are very concentrated around a mean with low variance, they are qualified as good candidates for the fundamental reference. Such reference could then be applied to measure the randomness of other Coronaviridae sequences. Our findings show that the relative randomness ratios are very consistent and concentrated. This result indicates their randomness is very stable and predictable. The findings also reveal the evolutional behaviours between the Coronaviridae and all its subfamilies. [ABSTRACT FROM AUTHOR]

Alcalase potato protein hydrolysate (APPH) might have a very important role in therapeutic effects. This study aims to examine the beneficial effects of bioactive peptides (DIKTNKPVIF [DI] and IF) from APPH supplement in the regulation of cardiac apoptosis, autophagy, and mitochondrial biogenesis pathway in spontaneously hypertensive rats (SHR). We have investigated ejection fraction, fractional shortening, Tunel assay, apoptosis, autophagy, and mitochondrial biogenesis pathway marker expression to show the efficacy of bioactive peptides in an SHR model. Bioactive peptides significantly upregulate ejection fraction and fractional shortening in SHR rats. SHR rats exhibited higher protein expression of apoptotic markers such as BAD, cytochrome c, and caspase 3. Finally, the bioactive peptides upregulate survival proteins (p‐AKT/p‐PI3K), autophagy (Beclin1/LC3B), and mitochondrial biogenesis (p‐AMPKα/SIRT1/PGC1α/p‐Foxo3a/Nrf2/CREB) marker expressions compared with the SHR groups. In summary, the bioactive peptides protect the heart tissues through the activation of autophagy and mitochondrial biogenesis pathway and thereby attenuate cardiac apoptosis in a spontaneously hypertensive rat model. [ABSTRACT FROM AUTHOR]

It has been well‐documented that the consumption of deep sea water (DSW) has beneficial effects on myocardial hypertrophy and cardiac apoptosis induced by hypercholesterolemia. However, the molecular mechanisms for the anti‐inflammatory effects of DSW on diabetic cardiomyopathy are still largely unclear. The main purpose of this present study was to test the hypothesis that DSW exerts anti‐inflammatory effects through the suppression of the TNF‐α‐mediated signaling pathways. IP injection of streptozotocin (STZ) at the dose of 65 mg/kg was used to establish a diabetes rat model. DSW mineral extracts that diluted in desalinated water were prepared in three different dosages and administered to the rats through gavages for 4 weeks. These dosages are DSW‐1X (equivalent to 37 mg Mg2+/kg/day), 2X (equivalent to 74 mg Mg2+/kg/day) and 3X (equivalent to 111 mg Mg2+ mg/kg/day). Immunofluorescence staining and Western blot showed that the protein expression level of TNF‐α was markedly higher in the STZ‐induced diabetic rat hearts than in the control group. Consequently, the phosphorylation levels of the TNF‐α‐modulated downstream signaling molecules and P38 mitogen‐activated protein kinases (MAPKs) were notably elevated in heart tissues of STZ‐induced diabetes. These higher phosphorylation levels subsequently upregulated NF‐κB‐modulated inflammatory mediators, such as cyclooxygenase (COX)‐II and inducible nitric oxide synthase (iNOS). However, treatment with DSW as well as MgSO4, the main mineral in DSW, significantly reversed all the alterations. These findings suggest that DSW has potential as a therapeutic agent for preventing diabetes‐related cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Pancreatic damage results in insufficient insulin secretion, leading to type 1 diabetes. Stem cell‐based therapy has recently shown potential in the treatment of type 1 diabetes. Resveratrol supplementation has demonstrated a beneficial effect in treating diabetes. This study investigates if adipose‐derived stem cells (ADSC), preconditioned with resveratrol, show better effects on experimental diabetic animals. Wistar rats were randomly divided into four groups including sham (normal rats), DM (diabetic rats induced by SZT injection), DM+ADSC (DM rats with receiving autologous ADSC transplantation) and DM+R‐ADSC (DM rats receiving resveratrol preconditioned ADSC). The experimental results show that SZT induced pancreatic damage (DM group), including reduction of islet size, fibrosis pathway activation, survival signaling suppression, and apoptotic pathway expression, lead to serum glucose elevation. Autologous ADSC (DM+ADSC group) transplantation shows improvement in the above observations in DM rats. Furthermore, ADSC precondition with resveratrol (DM+R‐ADSC group) reveals significant improvement in the above pathological observations over both DM and DM+ADSC groups. We found that ADSC precondition with resveratrol increases the survival marker p‐Akt expression, leading to enhanced ADSC viability. This study suggests that ADSC precondition with resveratrol shows potential in the treatment of patients with type 1 DM. [ABSTRACT FROM AUTHOR]

Carboxyl‐terminus of Hsc70 interacting protein (CHIP) is a chaperone‐dependent E3‐ubiquitin ligase with important function in protein quality control system. In the current research endeavor, we have investigated the putative role of CHIP in lipopolysaccharides (LPS)‐induced cardiomyopathies. Basically, H9c2 cardiomyoblasts were transfected with CHIP for 24 hr, and thereafter, treated with LPS for 12 hr. Concomitantly, western blot analysis, actin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and coimmunoprecipitation studies were performed to investigate the underlying intricacies. Interestingly, western blot analysis revealed that the expression of hypertrophy and apoptosis‐related proteins were considerably reduced following overexpression of CHIP. Moreover, Actin staining and TUNEL assay further ascertained the attenuation of cardiac hypertrophy and apoptosis following overexpression of CHIP respectively. These aspects instigate the role of CHIP in attenuation of LPS‐induced cardiomyopathies. Additionally and importantly, co‐immunoprecipitation and western blot studies revealed that CHIP plausibly promotes degradation of nuclear factor of activated T cells 3 (NFATc3) through ubiquitin‐proteasomal pathway. Taken together, our study reveals that CHIP attenuates LPS‐induced cardiac hypertrophy and apoptosis perhaps by promoting NFATc3 proteasomal degradation. [ABSTRACT FROM AUTHOR]

A vector autoregression (VAR) model is powerful for analyzing economic data as it can be used to simultaneously handle multiple time series from different sources. However, in the VAR model, we need to address the problem of substantial coefficient dimensionality, which would cause some computational problems for coefficient inference. To reduce the dimensionality, one could take model structures into account based on prior knowledge. In this paper, group structures of the coefficient matrices are considered. Because of the different types of VAR structures, corresponding Markov chain Monte Carlo algorithms are proposed to generate posterior samples for performing inference of the structure selection. Simulation studies and a real example are used to demonstrate the performances of the proposed Bayesian approaches. [ABSTRACT FROM AUTHOR]

Adipose‐derived mesenchymal stem cells (ADMSCs) are easily accessible and are attractive mesenchymal stem cells for use in regenerative medicine; however their application is frequently restricted due to various challenges present in the environment they are administered. Therefore ADMSCs are preferably preconditioned with various stimulating factors to overcome the barriers developed in any pathological conditions. Here we used ADMSCs from rat adipose based on the abundance of positive markers and preconditioned the cells with extracts from Alpinate Oxyphyllae Fructus (AOF), a traditional Chinese herb used for antiaging, associated various health benefits. The preconditioned stem cells were tested for their potential to drive H9c2 from doxorubicin (Dox)‐induced aging. The AOF‐treated stem cells enriched stemness in ADMSCs with respect to their stem cells' positive marker, and enhanced their longevity mechanism and elevated the stem cell homing‐associated C‐X‐C chemokine receptor type 7 (CXCR7). The AOF preconditioned stem cells, when cocultured with H9c2 cells, showed effective protection to Dox‐induced senescence and stem cell homing to damaged H9c2 cells. The presence of AOF provided greater protective effects in the Dox environment. In addition, AOF‐pretreated ADMSCs showed enhanced migration than those treated with AOF in Dox environment. Therefore, our results show that administration of AOF preconditioned stem cells is potentially an effective strategy in the management of aging‐associated cardiac disorders. Adipose‐derived mesenchymal stem cells (ADMSCs) preconditioned with Alpinate Oxyphyllae Fructus (AOF) protected H9c2 cells against doxorubicin (Dox) induced senescence by improving cell survival and longevity and by elevating the stem cell migration toward damaged H9c2 cells and upregulating the expression of homing‐associated C‐X‐C chemokine receptor type 7 (CXCR7). [ABSTRACT FROM AUTHOR]

Haemorrhagic shock and resuscitation (HS/R) may cause global ischaemia‐reperfusion injury, which can result in systemic inflammation, multiorgan failure (particularly liver failure) and high mortality. Hinokitiol, a bioactive tropolone‐related compound, exhibits antiplatelet and anti‐inflammatory activities. Targeting inflammatory responses is a potential strategy for ameliorating hepatic injury during HS/R. Whether hinokitiol prevents hepatic injury during HS/R remains unclear. In the present study, we determined the role of hinokitiol following HS/R. The in vivo assays revealed that hinokitiol markedly attenuated HS/R‐induced hepatic injury. Hinokitiol could inhibited NF‐κB activation and IL‐6 and TNF‐α upregulation in liver tissues. Moreover, hinokitiol reduced caspase‐3 activation, upregulated Bax and downregulated Bcl‐2. These findings suggest that hinokitiol can ameliorate liver injury following HS/R, partly through suppression of inflammation and apoptosis. Furthermore, the in vitro data revealed that hinokitiol significantly reversed hypoxia/reoxygenation (H/R)‐induced cell death and apoptosis in the primary hepatocytes. Hinokitiol prevented H/R‐induced caspase‐3 activation, PPAR cleavage, Bax overexpression and Bcl‐2 downregulation. Moreover, hinokitiol attenuated H/R‐stimulated NF‐κB activation and reduced the levels of IL‐6 and TNF‐α mRNAs, suggesting that hinokitiol can protect hepatocytes from H/R injury. Collectively, our data suggest that hinokitiol attenuates liver injury following HS/R, partly through the inhibition of NF‐κB activation. [ABSTRACT FROM AUTHOR]

We show how to define a plethora of metrics for graphs—either full graphs or subgraphs. The method mainly utilizes the minimal matching between any two multisets of positive real numbers by comparing the multiple edges with respect to their corresponding vertices. In the end of this article, we also demonstrate how to implement these defined metrics with the help of adjacency matrices. These metrics are easy to be manipulated in real applications and could be amended according to different situations. By our metrics, one should be able to compare the distances between graphs, trees, and networks, in particular those with fuzzy properties. [ABSTRACT FROM AUTHOR]

IGF‐IIR activation regulates cardiac remodeling leading to apoptosis. Here, we identified the novel IGF‐IIRα (150 KDa), a truncated IGF‐IIR transcript enhances cardiac apoptosis under high‐salt uptake in transgenic rat model. Echocardiographic analysis revealed decline in ejection fraction and fractional shortening percentage in IGF‐IIRα (TG) rats. We found that IGF‐IIRα TG rats developed severe apoptosis and fibrosis as identified through TUNEL assay and Masson's trichrome staining. Importantly, the heart functioning, apoptosis, and fibrosis were significantly affected under high‐salt conditions in IGF‐IIRα (TG) rats. Significant upregulation of apoptosis was evident from decreased Bcl‐2, p‐AKT, and p‐PI3K expressions with concomitant increase in Bad, cytochrome C, cleaved caspase 3 levels. We found that, IGF‐IIRα highly induced tissue fibrosis through collagen accumulation (col I, col III) and up regulated various fibrotic markers such as tPA, uPA, TGF‐β, and vimentin expressions. The observed upregulation of fibrosis were significantly regulated under high‐salt conditions and their over regulation under IGF‐IIRα over expressions shows the key role of IGF‐IIRα in promoting high‐salt induced fibrosis. During IGF‐IIRα over expression induced cardiotoxicity, under high salt condition, and it destroys the interaction between CHIP and HSF1, which promotes the degradation of HSF1 and results in upregulation of IGF‐IIR/IGF‐IIRα expressions. Altogether, the study unveils novel IGF‐IIRα in the regulation of cardiac apoptosis and fibrosis under high‐salt diet. [ABSTRACT FROM AUTHOR]

Increasing reports on epidemiological, diagnostic, and clinical studies suggest that dysfunction of the inflammatory reaction results in chronic illnesses such as cancer, arthritis, arteriosclerosis, neurological disorders, liver diseases, and renal disorders. Chronic inflammation might progress if injurious agent persists; however, more typically than not, the response is chronic from the start. Distinct to most changes in acute inflammation, chronic inflammation is characterized by the infiltration of damaged tissue by mononuclear cells like macrophages, lymphocytes, and plasma cells, in addition to tissue destruction and attempts to repair. Phagocytes are the key players in the chronic inflammatory response. However, the important drawback is the activation of pathological phagocytes, which might result from continued tissue damage and lead to harmful diseases. The longer the inflammation persists, the greater the chance for the establishment of human diseases. The aim of this review was to focus on advances in the understanding of chronic inflammation and to summarize the impact and involvement of inflammatory agents in certain human diseases. [ABSTRACT FROM AUTHOR]

Abstract: The intensity‐scan (I‐scan) technique to study the polarization‐dependent, nonlinear processes in exfoliated bulk ReS2 is utilized. The polarization‐dependent reflection and transmission of ReS2, from which the absorption coefficients are extracted using the transfer matrix method, are measured. Absorption coefficients under high laser peak power show a transition from saturable absorption (SA) to reverse saturable absorption when rotating the laser polarization with respect to the b‐axis. It is found that SA and excited‐state absorption (ESA) contribute to the nonlinear optical processes. Both the SA and ESA show strong dependence on the polarization angle, which is attributed to the anisotropic optical transition probability and electronic band structure in ReS2. The anisotropic nonlinear optical properties of ReS2 may find applications as saturable absorbers in lasers and optical modulators. [ABSTRACT FROM AUTHOR]

Abstract: Cardiomyocyte apoptosis is the major risk factor for the development of heart failure (HF). The purpose of this study was to evaluate the effects of Gamma‐aminobutyric acid (GABA) tea on hypertension‐induced cardiac apoptotic pathways in spontaneously hypertensive rats (SHR). In order to reveal the mechanisms, 36 male SHR at eight weeks of age, 200 g were divided into six groups. One group was fed water as a control group. Other rats were administered one of the following treatments: GABA tea at dose 150 and 300 mg/kg/day as low GABA tea (LGT) and high GABA tea (HGT) groups, respectively, pure GABA at dose 150 and 300 mg/kg/day as LG and HG groups, respectively, green tea (GT) as control of LGT and HGT groups. After 12 weeks, cardiac tissues were analyzed by histological analysis, western blotting, and TUNEL assays. GABA tea, GT, and pure GABA decreased hypertension‐induced cardiac abnormalities, including abnormal myocardial architecture. In addition, GABA tea, GT, and pure GABA dramatically increased anti‐apoptotic protein, Bcl2. Furthermore, GABA tea, GT, and pure GABA also decreased activated‐caspase 9 and activated‐caspase 3. Additionally, the survival associated protein IGF‐I and PI3K/Akt were enhanced in cardiac tissues upon treatment. Our results showed an optimistic anti‐apoptotic and pro‐survival effects of GABA tea treatment against hypertensive rat hearts. [ABSTRACT FROM AUTHOR]

Purpose: To assess the reduction of 6 and 12 months postoperatively of Framingham risk score in morbidly obese patients with laparoscopic sleeve gastrectomy (LSG).Material and methods: In total, 870 morbid obesity patients received LSG in Taipei Medical University Hospital from June 2007 to June 2014 were retrospectively studied preoperatively, 6 and 12 months after surgery. The coronary heart disease risk was calculated using Framingham risk score.Results: The body mass index in men and women decreased from 43.3 ± 6.9, 39.2 ± 6.0 kg/m2 preoperatively to 32.9 ± 6.7, 31.0 ± 5.2 kg/m2 and to 30.4 ± 5.6 , 28.2 ± 4.7 kg/m2, respectively, at 6 and 12 months after surgery (P < 0.0001). At 6 and 12 months after LSG, there was a marked improvement on lipid profile as well as a significant decline in the prevalence of diabetes mellitus, systemic hypertension, and smoking. The Framingham risk score in men and women reduced from 3.2 ± 5.7, 6.1 ± 5.7 preoperatively to 1.4 ± 5.9, 3.3 ± 5.9 and 0.1 ± 6.2, 2.8 ± 6.1, respectively, at 6 and 12 months after surgery (P < 0.0001).Conclusions: Laparoscopic sleeve gastrectomy is efficient not only in the reduction of obesity and its related comorbidities but also in decreasing the long-term coronary event risk. Early intervention for the high-risk group is strongly recommended. [ABSTRACT FROM AUTHOR]

Abstract: Silicon‐organic hybrid integrated devices show great potential in high‐speed optical interconnects and sensors. In this paper, a high‐speed modulator based on an electro‐optic (EO) polymer (SEO125) infiltrated sub‐wavelength grating (SWG) waveguide ring resonator is presented. The core of the SWG waveguide consists of periodically arranged silicon pillars along the light propagation direction, which provides large mode volume overlap with EO polymer. The optimized SWG shows a mode volume overlap of 36.2% with a silicon duty cycle of 0.7. The 3‐dB modulation bandwidth of the fabricated modulator is measured to be larger than 40 GHz occupying an area of 70 μm x 29 μm, which is the largest bandwidth and the most compact footprint that has been demonstrated for ring resonators on the silicon‐organic hybrid platform. [ABSTRACT FROM AUTHOR]

Abstract: Colorectal cancer (CRC) is one of the most common cancers and causes of cancer‐related death. There are several first‐line chemotherapeutic drugs used to treat CRC. Oxaliplatin (OXA) is an alkylating cytotoxic agent that is usually combined with other chemotherapeutic drugs to treat stage II and stage III CRC. However, cancer cells commonly acquire multidrug resistance (MDR), which is a major obstruction to cancer treatment. Recent studies have shown that natural components from traditional Chinese medicine or foods that have many biological functions may be new adjuvant therapies in clinical trials. We challenged LoVo CRC cell lines with OXA in a dose‐dependent manner to create an OXA‐resistant model. The expression of ABCG2 was significantly higher, and levels of endoplasmic reticulum (ER) stress markers were lower than those Parental cells. However, Lupeol, which is found in fruits and vegetables, has been shown to have bioactive properties, including anti‐tumor properties that are relevant to many diseases. In our study, Lupeol downregulated cell viability and activated cell apoptosis. Moreover, Lupeol decreased the expression of ABCG2 and activated ER stress to induce OXA‐resistant cell death. Importantly, the anti‐tumor effect of Lupeol in OXA‐resistant cells was higher than that of LoVo Parental cells. In addition, we also confirmed our results with a xenograft animal model, and the tumor size significantly decreased after Lupeol injections. Our findings show that Lupeol served as a strong chemoresistant sensitizer and could be a new adjuvant therapy method for chemoresistant patients. [ABSTRACT FROM AUTHOR]

Cardiomyocyte death is an important pathogenic feature of ischemia and heart failure. Through this study, we showed the synergistic role of HIF-1α and FoxO3a in cardiomyocyte apoptosis subjected to hypoxia plus elevated glucose levels. Using gene specific small interfering RNAs (siRNA), semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR), Western blot, immunofluorescence, nuclear and cytosolic localization and TUNEL assay techniques, we determined that combined function of HIF-1α and FoxO3a under high glucose plus hypoxia condition lead to enhanced expression of BNIP3 inducing cardiomyocyte death. Our results highlighted the importance of the synergistic role of HIF-1α and FoxO3a in cardiomyocyte death which may add insight into therapeutic approaches to pathophysiology associated with ischemic diabetic cardiomyopathies. [ABSTRACT FROM AUTHOR]

Abstract: The physiological regulation of Oestrogen receptor α (ERα) and peroxisome proliferator‐activated receptor alpha (PPARα) in Hepatocellular carcinoma (HCC) remains unknown. The present study we first treat the cells with fenofibrate and further investigated the possible mechanisms of 17β‐estradiol (E2) and/or ERα on regulating PPARα expression. We also found higher PPARα expression in the tumor area than adjacent areas and subsequently compared PPARα expression in four different hepatic cancer cell lines. Hep3B cells were found to express more PPARα than the other cell lines. Using the PPARα agonist fenofibrate, we found that fenofibrate increased Hep3B cell proliferation efficiency by increasing cell cycle proteins, such as cyclin D1 and PCNA, and inhibiting p27 and caspase 3 expressions. Next, we performed transient transfections and immuno‐precipitation studies using the pTRE2/ERα plasmid to evaluate the interaction between ERα and PPARα. ERα interacted directly with PPARα and negatively regulated its function. Moreover, in Tet‐on ERα over‐expressed Hep3B cells, E2 treatment inhibited PPARα, its downstream gene acyl‐CoA oxidase (ACO), cyclin D1 and PCNA expression and further increased p27 and caspase 3 expressions. However, over‐expressed ERα plus 17‐β‐estradiol (10−8 M) reversed the fenofibrate effect and induced apoptosis, which was blocked in ICI/melatonin/fenofibrate‐treated cells. This study illustrates that PPARα expression and function were negatively regulated by ERα expression in Hep3B cells. [ABSTRACT FROM AUTHOR]

Abstract: Tea, the most widely consumed natural beverage has been associated with reduced mortality risk from cardiovascular disease. Oolong tea is a partially fermented tea containing high levels of catechins, their degree of oxidation varies between 20%‐80% causing differences in their active metabolites. In this study we examined the effect of oolong tea extract (OTE) obtained by oxidation at low‐temperature for short‐time against hypoxic injury and found that oolong tea provides cyto‐protective effects by suppressing the JNK mediated hypertrophic effects and by enhancing the innate antioxidant mechanisms in neonatal cardiomyocytes and in H9c2 cells. OTE effectively attenuates 24 h hypoxia‐triggered cardiomyocyte loss by suppressing caspase‐3‐cleavage and apoptosis in a dose‐dependent manner. OTE also enhances the IGFIR/p‐Akt associated survival‐mechanism involving the elevation of p‐Badser136 in a dose‐dependent manner to aid cellular adaptations against hypoxic challenge. The results show the effects and mechanism of Oolong tea to provide cardio‐protective benefits during hypoxic conditions. [ABSTRACT FROM AUTHOR]

Hypertension-induced cardiac hypertrophy and apoptosis are major characteristics of earlystage heart failure (HF). Inhibition of extracellular signal-regulated kinases (ERK) efficaciously suppressed angiotensin II (ANG II)-induced cardiomyocyte hypertrophy and apoptosis by blocking insulin-like growth factor II receptor (IGF-IIR) signaling. However, the detailed mechanism by which ANG II induces ERK-mediated IGF-IIR signaling remains elusive. Here, we found that ANG II activated ERK to upregulate IGF-IIR expression via the angiotensin II type I receptor (AT1R). ERK activation subsequently phosphorylates HSF1 at serine 307, leading to a secondary phosphorylation by glycogen synthase kinase III (GSK3) at serine 303. Moreover, we found thatANGII mediated ERK/GSK3-induced IGF-IIR protein stability by downregulating the E3 ubiquitin ligase of IGF-IIR RING finger protein CXXVI (RNF126). The expression of RNF126 decreased following ANG II-induced HSF1S303 phosphorylation, resulting in IGF-IIR protein stability and increased cardiomyocyte injury. Inhibition of GSK3 significantly alleviated ANG IIinduced cardiac hypertrophy in vivo and in vitro. Taken together, these results suggest that HSF1 phosphorylation stabilizes IGF-IIR protein stability by downregulating RNF126 during cardiac hypertrophy. ANG II activates ERK/GSK3 to phosphorylate HSF1, resulting in RNF126 degradation, which stabilizes IGF-IIR protein expression and eventually results in cardiac hypertrophy. HSF1 could be a valuable therapeutic target for cardiac diseases among hypertensive patients. [ABSTRACT FROM AUTHOR]

In recent years, neuropathological and epidemiological studies have indicated an association between Alzheimer's disease (AD) and several cardiovascular risk factors. In this study, the cardio-protective effects of folic acid (FA) in early stage AD was elucidated using a triple-transgenic (3xTg) Alzheimer's mouse model. Eleven-month-old C57BL/6 mice and 3xTg mice were assigned to five groups. During the four-month treatment period, the low-FA treatment group received FA through their diet, and the high-FA treatment groups received 3 mg/dl folate in drinking water and were also gastric-fed 1.2 mg/kg folate every day. In the C57B1/6J mice, treatment with high doses of FA (HFA) did not show any considerable effect compared to the control group or the low-dose dietary FA treatment group. However, Alzheimer's mice treated with HFA showed enhanced cardio-protection. Western blot analysis revealed that FA treatment restored SIRT1 expression, which was suppressed in 3xTg mice, through enhanced AMPK expression. FA significantly enhanced the IGF1 receptor survival mechanism in the hearts of the 3xTg mice and suppressed the expression-intrinsic and extrinsic apoptosis-associated proteins. The results suggest that FA intake may significantly alleviate cellular pathological events in the heart associated with AD. [ABSTRACT FROM AUTHOR]

ABSTRACT Background and objective Parapneumonic effusion ( PPE) is commonly caused by Gram-positive bacteria ( GPB) and often presents with pleural loculation, which is characterized by overproduction of plasminogen activator inhibitor ( PAI)-1. Lipoteichoic acid ( LTA), a surface adhesion molecule of GPB, binds to the pleural mesothelium and triggers inflammation. However, the effects of LTA on PAI-1 expression in PPE and underlying mechanisms remain unclear. Methods Thirty consecutive patients with PPE were enrolled, including uncomplicated culture negative ( CN, n = 11), Gram-negative bacteria ( GNB, n = 7) and GPB ( n = 12) groups stratified by pleural fluid characteristics and bacteriology, and the effusion PAI-1 levels were measured. In addition, human pleural mesothelial cells ( PMC) were treated with LTA and the expression of PAI-1 and activation of signalling pathways were assayed. Results The median levels of PAI-1 were significantly higher in GPB (160.5 ng/ mL) and GNB (117.0 ng/ mL) groups than in the uncomplicated CN (58.0 ng/ mL) group. In human PMC, LTA markedly upregulated PAI-1 mRNA and protein expression and enhanced elaboration of Toll-like receptor 2 ( TLR2). Furthermore, LTA increased c-Jun N-terminal kinase ( JNK) phosphorylation, induced activating transcription factor 2 ( ATF2)/c-Jun nuclear translocation and activated PAI-1 promoter activity. Pretreatment with TLR2 siRNA significantly inhibited LTA-induced JNK phosphorylation and PAI-1 protein expression. Conclusion Culture-positive PPE, especially that caused by GPB, has a significantly higher level of PAI-1 than uncomplicated CN PPE. LTA upregulates PAI-1 expression through activation of TLR2/ JNK/activator protein 1 ( AP-1) pathway in human PMC. Better understanding of the modulation of PAI-1 synthesis by LTA in PPE may provide potential therapies for infected pleural effusions. [ABSTRACT FROM AUTHOR]

In our previous study palmitic acid (PA) induced lipotoxicity and switches energy metabolism from CD36 to GLUT4 in H9c2 cells. Low level of high density lipoprotein (HDL) is an independent risk factor for cardiac hypertrophy. Therefore, we in the present study investigated whether HDL can reverse PA induced lipotoxicity in H9c2 cardiomyoblast cells. In this study, we treated H9c2 cells with PA to create a hyperlipidemia model in vitro and analyzed for CD36 and GLUT4 metabolic pathway proteins. CD36 metabolic pathway proteins (phospho-AMPK, SIRT1, PGC1α, PPARα, CPT1β, and CD36) were decreased by high PA (150 and 200 μg/μl) concentration. Interestingly, expression of GLUT4 metabolic pathway proteins (p-PI3K and pAKT) were increased at low concentration (50 μg/μl) and decreased at high PA concentration. Whereas, phospho-PKCζ, GLUT4 and PDH proteins expression was increased in a dose dependent manner. PA treated H9c2 cells were treated with HDL and analyzed for cell viability. Results showed that HDL treatment induced cell proliferation efficiency in PA treated cells. In addition, HDL reversed the metabolic effects of PA:CD36translocation was increased and reducedGLUT4translocation, but HDL treatment significantly increased CD36 metabolic pathway proteins and reduced GLUT4 pathway proteins. Rat neonatal cardiomyocytes showed similar results. In conclusion, HDL reversed palmatic acid-induced lipotoxicity and energy metabolism imbalance in H9c2 cardiomyoblast cells and in neonatal rat cardiomyocyte cells. [ABSTRACT FROM AUTHOR]