1,134 research outputs found

    Increased expression of pigment epithelium-derived factor in aged mesenchymal stem cells impairs their therapeutic efficacy for attenuating myocardial infarction injury.

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    AIMS: Mesenchymal stem cells (MSCs) can ameliorate myocardial infarction (MI) injury. However, older-donor MSCs seem less efficacious than those from younger donors, and the contributing underlying mechanisms remain unknown. Here, we determine how age-related expression of pigment epithelium-derived factor (PEDF) affects MSC therapeutic efficacy for MI. METHODS AND RESULTS: Reverse transcriptase-polymerized chain reaction and enzyme-linked immunosorbent assay analyses revealed dramatically increased PEDF expression in MSCs from old mice compared to young mice. Morphological and functional experiments demonstrated significantly impaired old MSC therapeutic efficacy compared with young MSCs in treatment of mice subjected to MI. Immunofluorescent staining demonstrated that administration of old MSCs compared with young MSCs resulted in an infarct region containing fewer endothelial cells, vascular smooth muscle cells, and macrophages, but more fibroblasts. Pigment epithelium-derived factor overexpression in young MSCs impaired the beneficial effects against MI injury, and induced cellular profile changes in the infarct region similar to administration of old MSCs. Knocking down PEDF expression in old MSCs improved MSC therapeutic efficacy, and induced a cellular profile similar to young MSCs administration. Studies in vitro showed that PEDF secreted by MSCs regulated the proliferation and migration of cardiac fibroblasts. CONCLUSIONS: This is the first evidence that paracrine factor PEDF plays critical role in the regulatory effects of MSCs against MI injury. Furthermore, the impaired therapeutic ability of aged MSCs is predominantly caused by increased PEDF secretion. These findings indicate PEDF as a promising novel genetic modification target for improving aged MSC therapeutic efficacy

    Reduced cardioprotective action of adiponectin in high-fat diet-induced type II diabetic mice and its underlying mechanisms.

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    Diabetes exacerbates ischemic heart disease morbidity and mortality via incompletely understood mechanisms. Although adiponectin (APN) reduces myocardial ischemia/reperfusion (MI/R) injury in nondiabetic animals, whether APN\u27s cardioprotective actions are altered in diabetes, a pathologic condition with endogenously reduced APN, has never been investigated. High-fat diet (HD)-induced diabetic mice and normal diet (ND) controls were subjected to MI via coronary artery ligation, and given vehicle or APN globular domain (gAPN, 2 μg/g) 10 min before reperfusion. Compared to ND mice (where gAPN exerted pronounced cardioprotection), HD mice manifested greater MI/R injury, and a tripled gAPN dose was requisite to achieve cardioprotective extent seen in ND mice (i.e., infarct size, apoptosis, and cardiac function). APN reduces MI/R injury via AMP-activated protein kinase (AMPK)-dependent metabolic regulation and AMPK-independent antioxidative/antinitrative pathways. Compared to ND, HD mice manifested significantly blunted gAPN-induced AMPK activation, basally and after MI/R (p\u3c0.05). Although both low- and high-dose gAPN equally attenuated MI/R-induced oxidative stress (i.e., NADPH oxidase expression and superoxide production) and nitrative stress (i.e., inducible nitric oxide synthase expression, nitric oxide production, and peroxynitrite formation) in ND mice, only high-dose gAPN efficaciously did so in HD mice. We demonstrate for the first time that HD-induced diabetes diminished both AMPK-dependent and AMPK-independent APN cardioprotection, suggesting an unreported diabetic heart APN resistance

    Risk Management in Insurance Companies

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    Insurance is the uncertain business in uncertain society. Today, insures face more complex and difficult risks. Efficient risk management mechanisms are essential for the insurers. The paper is set out initially to explore UK insurance companies risk management and risk disclosure by examining companies annual report after all the listed insurance companies are required to disclose risk information in their annual report, which seeks to reflect the recent development in UK insurance companies practices on risk management and risk disclosure. In particular, the author sought to understand: companies compliance with IFRS 4 on the requirement of risk disclosure; the rationale of companies risk management practice; the development of risk management in terms of risk management function improvement and risk management process development; and how all these issues are influenced by a companys nature. The main findings are regulators requirements could have a significant effect, and companies risk management and risk disclosure subject to their nature

    Establishment of reference intervals of thyroid-related hormones for adults with normal liver function in Zhejiang Province by indirect method

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    ObjectiveThyroid disorders are prevalently diagnosed yet face significant challenges in their accurate identification in China. Predominantly, the reference intervals (RIs) currently in use across Chinese medical facilities derive from company-provided data, lacking stringent scientific validation. This practice underscores the urgent necessity for establishing tailored RIs for thyroid-related hormones, specifically tailored to the coastal area populations. Such refined RIs are imperative for empowering clinicians with the precise tools needed for the accurate diagnosis of both overt and subclinical thyroid conditions.MethodsThis investigation analyzed the medical histories of 6021 euthyroid individuals mainly from East coastal area of China between June 2019 and December 2020. The cohort comprised residents of coastal areas, focusing on extracting insights into the regional specificity of thyroid hormone levels. A thorough examination protocol was implemented, encompassing inquiries into thyroid health history, ultrasound screenings, palpations during thyroid surgery, detections of thyroid antibodies, and reviews of medication histories. Adherence to the CLSI C28-A3 guidelines facilitated the derivation of RIs for thyroid-related hormones, subsequently juxtaposed against those provided by commercial entities.ResultsThe study delineated the following gender- and age-specific RIs for Thyroid-Stimulating Hormone (TSH): for males under 50 years, 0.57-3.37; males over 50 years, 0.51-4.03; females under 50 years, 0.53-3.91; and females over 50 years, 0.63-4.31. Further analysis revealed the RIs for Free Thyroxine (FT4), Free Triiodothyronine (FT3), Total Thyroxine (TT4), and Total Triiodothyronine (TT3) amongst males and females, with notable distinctions observed between the two genders and across age brackets. These findings are in stark contrast to the standardized intervals provided by manufacturers, particularly highlighting differences in TT3 and FT3 levels between genders and a tendency for TSH levels to increase with age.ConclusionThis research successfully establishes refined RIs for thyroid-related hormones within the Chinese coastal area populations, taking into account critical demographic factors such as gender and age. These tailored RIs are anticipated to significantly enhance the diagnostic accuracy for thyroid diseases, addressing the previously noted discrepancies with manufacturer-provided data and underscoring the importance of regionally and demographically adjusted reference intervals in clinical practice

    Does urban–rural integration contribute to environmental health? Exploring the interplay between urban–rural integration and air quality dynamics in Yangtze River middle reaches city cluster

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    BackgroundExploring the coordinated relationship between urban–rural integration and air quality has significant implications for promoting urban–rural development, preventing air pollution and ensuring residents’ health. This study takes Yangtze River middle reaches city cluster as a case study, calculates the levels of urban–rural integration and air quality development, analyzes their coupled coordination relationship and driving factors, and explores the path of coordinated development.MethodsThis study constructs a coupling coordination degree model to analyze the relationship between the urban–rural integration development level and air quality development level. We use the trend surface method to analyze the spatial divergence characteristics of the coordination degree between urban–rural integration and air quality. In addition, we used a geographic detector to analyze the factors affecting the coordination degree.Results(1) The overall level of urban–rural integration development showed an upward trend. High-value regions were concentrated in the Wuhan, Chang-Zhu-Tan, and Nanchang metropolitan areas. (2) The Air Quality Index showed an overall decline, with the most significant improvements observed in Wuhan, Changsha, and Jiujiang. (3) The coupling degree increased from 0.570 in 2013 to 0.794 in 2021, and the coordination degree increased from 0.337 in 2013 to 0.591 in 2021. The link between urban–rural integration and air quality has deepened over time, and the two promote each other, making city cluster develop towards environmental friendliness. The spatial distribution of coordination degree shows a “high in the west and low in the east, high in the north and low in the south” trend. (4) Per capita GDP, non-agricultural employment ratio, urban–rural spatial circulation media, population urbanization level, and fixed asset investment were identified as the core factors driving the coordination degree between urban–rural integration and air quality.ConclusionThis study confirms that the urban–rural integration and air quality of Yangtze River middle reaches city cluster are gradually changing in the direction of high-quality coordination. However, there are great differences among cities, regional imbalance is prominent, and coordination degree is driven by multidimensional factors

    Cloning and analysis of plant fatty acid desaturase 7 gene promoter from Brassica napus

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    In order to investigate the regulation mode of Brassica napus FAD7 gene in response of thermal stress, we measured the protein levels of BnFAD7 in plant at low and high temperature, and then analyzed promoter activity of 5’-flanking regions of BnFAD7 by transient gene expression in B. napus protoplasts at different temperatures. Our studies indicated that no significant change occurred in the expression level of BnFAD7 both at high and low temperature, while BnFAD7 promoter showed a heat-induced regulation mode and slowly increased activity at the chilling conditions, which suggested there are heat-induced cis-action element lies in BnFAD7 promoter sequence. Our data also suggested that a post-transcription regulation pattern existed to ensure BnFAD7 function in the acclimation to temperature stress. Furthermore, our studies give new evidence for the hypothesis that BnFAD7 and BnFAD8 gene may come from the same ancestor gene.Keywords: Brassica napus, fatty acids desaturase, promoter analysis, transient expression, BnFAD

    Trifolirhizin relieves renal injury in a diabetic nephropathy model by inducing autophagy and inhibiting oxidative stress through the regulation of PI3K/AKT/mTOR pathway

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    Purpose: To evaluate the effects of trifolirhizin on diabetic nephropathy (DN), and the mechanism of action. Methods: Male db/db mice (8 weeks, n = 24) and age-matched control mice (n = 6) were obtained. The mice were further divided into four groups and administered increasing doses of trifolirhizin (0, 12.5, 25 and 50 mg/kg). Histological analysis of renal tissues were performed by H & E staining. Blood urea nitrogen (BUN) and creatinine were determined using enzyme-linked immunosorbent assay (ELISA). Immunoblot and TUNEL assay were performed to investigate the effect of trifolirhizin on autophagy and apoptosis, while ELISA and dihydroethidium (DHE) staining were conducted to evaluate reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) levels. The effect of trifolirhizin on PI3K/AKT/mTOR pathway was determined using Immunoblot assays. Results: Trifolirhizin alleviated renal injury in diabetic mice, and also activate autophagy and inhibited apoptosis in the renal tissues in diabetic mice (p < 0.001). In addition, trifolirhizin inhibited the oxidative stress response in the renal tissue in diabetic mice (p < 0.001). Trifolirhizin further inhibited PI3K/AKT/mTOR pathway and therefore relieved renal injury in the diabetic nephropathy model (p < 0.001). Conclusion: Trifolirhizin alleviates renal injury in diabetic mice, activates autophagy, and inhibits apoptosis in renal tissue of diabetic mice. Therefore, trifolirhizin is a promising a promising drug for the treatment of DN
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