查看更多>>摘要：Sepsis remains one of the main causes of death in intensive care unit (ICU) worldwide, despite all technological and scientific advances. Microvesicles (MV) have become promising biomarkers for quick and accurate monitoring of several illnesses. The aim of this pilot study was to characterize and evaluate the performance of MV as biomarker of clinical outcome in septic and trauma patients. For this purpose, 39 subjects, both genders, aging from 18 to 85 years were included in three groups referred as Sepsis, Trauma and Healthy Control. Kinetic analysis of MV was carried out at four consecutive time points: admission (baseline)/T1, 24 h/T2, 72 h/T3 and outcome/T4 of discharge or death. At admission, an overall increase in total MV (Annexin V~+) was observed in Sepsis.MV CD14~+ (monocytes) was a putative biomarker to identify trauma patients, while MV CD3~+ (T-cells) and CD41~+ (platelets) were qualified to discriminated Trauma from Sepsis. Sepsis (Death) presented an increase in MV Annexin V~+, CD45~+, CD16~+, CD14~+, and CD41~+ in comparison to Sepsis (Discharge). Moreover, Trauma (Death) presented an increase of MV CD3+ and CD235+ as compared to Trauma (Discharge). Analysing the ROC curve of specific MV evaluated according to performance, an accuracy of 100% was found to segregate the outcome in sepsis, and 95% in trauma. Our findings suggest that MV might be useful as a potential role in discriminating outcome in patients with sepsis/septic shock and trauma with high accuracy. However, further studies with a larger number of participants will be necessary to validate our findings.
查看更多>>摘要：Objectives: Accumulating studies revealed that 6-gingerol, a compound extracted mainly from ginger, treats obesity by preventing hyperlipidemia in vivo induced by high-fat-diet (HFD). The present study intends to further evaluate the efficacy of 6-gingerol in the treatment of obesity and investigate its potential mechanism. Methods: Obese mice were established by HFD induction. Bioinformatic analysis was used to predict the possible pathways enrolled by the application of 6-gingerol. Body weight and the levels of blood glucose and lipids were examined and analyzed for the evaluation of the therapeutic effect of 6-gingerol. The size and amounts as well as the status of adipocytes were determined by histological staining. The expression levels of related proteins in adipose tissue were assessed by immunohistochemical staining, immunofluorescent staining, and Western blot analysis. In addition, the expression levels of related mRNA were assessed by RT-qPCR. Results: HFD induced obesity was significantly curbed by 6-gingerol treatment. Here inhibition mechanism of 6-gingerol is demonstrated on excessive hypertrophy and hyperplasia of adipocytes in white adipose tissue (WAT), which may be related to the regulation of adipocytokines, such as PPARγ, C/EBPα, FABP4 and adiponectin, and the TLR3/IL-6/JAK1/STAT3 axis. Moreover, 6-gingerol treatment suppressed the expressions of IL-1β and CD68 in the liver and AKT/INSR/IRS-1 in epididymal WAT. Conclusion: The results suggested that 6-gingerol could alleviate metabolic inflammation in the liver and insulin resistance to treat obesity. The mechanism is mainly involved in the inhibition of excessive hypertrophy and hyperplasia of adipocytes.
V. GopinathS. Manjunath KamathS. PriyadarshiniZamri Chik...
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查看更多>>摘要：The emergence of clinical complications and therapeutic challenges for treating various diseases necessitate the discovery of novel restorative functional materials. Polymer-based drug delivery systems have been extensively reported in the last two decades. Recently, there has been an increasing interest in the progression of natural biopolymers based controlled therapeutic strategies, especially in drug delivery and tissue engineering applications. However, the solubility and functionalisation due to their complex network structure and intramolecular bonding seem challenging. This review explores the current advancement and prospects of the most promising natural polymers such as cellulose, starch and their derivatives-based drug delivery vehicles like hydrogels, films and composites, in combating major ailments such as bone infections, microbial infections, and cancers. In addition, selective drug targeting using metal-drug (MD) and MD-based polymeric missiles have been exciting but challenging for its application in cancer therapeutics. Owing to high biocompatibility of starch and cellulose, these materials have been extensively evaluated in biomedical and pharmaceutical applications. This review presents a detailed impression of the current trends for the construction of biopolymer-based tissue engineering, drug/gene/protein delivery vehicles.
Abderrahim NemmarSuhail Al-SalamSumaya BeegamNur Elena Zaaba...
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查看更多>>摘要：Waterpipe tobacco smoking has gained worldwide popularity, particularly among youths. Several clinical and experimental studies have reported that waterpipe smoking (WPS) injures the cardiovascular system. However, the impact of smoking cessation (CS) on the cardiovascular toxicity induced by WPS received scant attention. Hence, we assessed, in C57BL/6 mice, the cardiovascular effects of WPS exposure for 3 months followed by 3 months of SC, as compared with mice exposed for either 3 months to WPS or air (control). WPS exposure induced hypertension, prothrombotic events both in vivo and in vitro and increased the plasma concentrations of tissue factor, fibrinogen and plasminogen activator inhibitor-1. These effects were significantly alleviated by SC. In heart tissue, the levels of troponin I, creatine kinase, lipid peroxidation, 8-isoprostane, tumor necrosis factor α, inteleukin 6, DNA damage and cleaved caspase-3 were significantly increased by WPS exposure. These actions were significantly reduced in the group of mice exposed to WPS followed by SC. Similarly, the increase in the level of nuclear factor κ-β induced by WPS exposure was significantly mitigated by SC. Immunohistochemical analysis of the hearts showed that WPS exposure increased the expression of nuclear factor erythroid-derived 2-like 2 by cardiomyocytes. The latter effect was significantly reduced by SC. Taken together, our data show that SC is associated with amelioration of WPS induced hypertension, prothrombotic events and cardiac oxidative stress, inflammation, DNA damage and apoptosis.
查看更多>>摘要：Cyanidin-3-rutinoside (C3R) is an anthocyanin with anti-diabetic properties found in red-purple fruits. However, the molecular mechanisms of C3R on Ca~2+-dependent insulin secretion remains unknown. This study aimed to identify C3R's mechanisms of action in pancreatic β-cells. Rat INS-1 cells were used to elucidate the effects of C3R on insulin secretion, intracellular Ca~2+ signaling, and gene expression. The results showed that C3R at 60, 100, and 300 μM concentrations significantly increased insulin secretion via intracellular Ca~2+ signaling. The exposure of cells with C3R concentrations up to 100 μM did not affect cell viability. Pretreatment of cells with nimodipine (voltage-dependent Ca~2+ channel (VDCC) blocker), U73122 (PLC inhibitor), and 2-APB (IP3 receptor blocker) inhibited the intracellular Ca~2+ signals by C3R. Interestingly, C3R increased intracellular Ca~2+ signals and insulin secretion after depletion of endoplasmic reticulum Ca~2+ stores by thapsigargin. However, insulin secretion was abolished under extracellular Ca~2+-free conditions. Moreover, C3R upregulated mRNA expression for Glut2 and Kir6.2 genes. These findings indicate that C3R stimulated insulin secretion by promoting Ca~2+ influx via VDCCs and activating the PLC-IP3 pathway. C3R also upregulates the expression of genes necessary for glucose-induced insulin secretion. This is the first study describing the molecular mechanisms by which C3R stimulates Ca~2+-dependent insulin secretion from pancreatic β-cells. These findings contribute to our understanding on how anthocyanins improve hyperglycemia in diabetic patients.
查看更多>>摘要：Red ginseng is a traditional Chinese herbal medicine that has long been used to treat diabetes, and its blood sugar-lowering activity has been confirmed. However, the mechanism of action of red ginseng on type 2 diabetes mellitus (T2DM) at the metabolic level is still unclear. The purpose of this study is to investigate the effect of red ginseng extract in the treatment of T2DM rats based on untargeted metabolomics. The rat model of T2DM was induced by a high-fat diet (HFD) combined with streptozotocin (STZ), and serum samples were collected after four weeks of treatment. The ultra-high-performance liquid chromatography coupled with Q Exactive HF-X Mass Spectrometer was used to analyze the level of metabolites in serum to evaluate the differences in metabolic levels between different groups. The results of biochemical analysis showed that red ginseng extract intervention significantly improved the levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), serum glucose (GLU), and fasting insulin (FINS) after four weeks. Orthogonal partial least squares discriminant analysis was used to study the overall changes of rat metabolomics. After the intervention of red ginseng extract, 50 biomarkers showed a callback trend. Metabolic pathway enrichment analysis showed that the regulated pathways were D-arginine and D-ornithine metabolism, D-glutamine and D-glutamate metabolism, taurine and hypotaurine metabolism, arginine biosynthesis, and tryptophan metabolism. Generally, the results demonstrated that red ginseng extract had beneficial effects on T2DM, which could be mediated via ameliorating the metabolic disorders.
查看更多>>摘要：Intestinal injury is one of the major side effects that are induced by medical radiation exposure, and has limited effective therapies. In this study, we investigated the beneficial effects of sanguinarine (SAN) on intestinal injury induced by ionizing radiation (IR) both in vitro and in vivo. Mice were exposed to whole abdominal irradiation (WAI) to mimic clinical scenarios. SAN was injected intraperitoneally to mitigate IR-induced injury. Histological examination was performed to assess the tissue injuries of the spleen and small intestine. A small intestinal epithelial cell line-6 (IEC-6) was analyzed for its viability and apoptosis in vitro under different treatments. Inflammation-related pathways and serum inflammatory cytokines were detected via Western blot analysis and ELISA, respectively. High-throughput sequencing was used to characterize the gut microbiota profile. High-performance liquid chromatography was performed to assess short-chain fatty acid contents in the colon. In vitro, SAN pretreatment protected cell viability and reduced apoptosis in IEC-6 cells. In vivo, SAN pretreatment protected immune organs, alleviated intestinal injury, and promoted intestinal recovery. SAN also reduced the levels of inflammatory cytokines, suppressed high mobility group box 1 (HMGB1)/ Toll-like receptor 4 (TLR4) pathway activation, and modulated gut microbiota composition. Our findings demonstrate that the beneficial properties of SAN alleviated intestinal radiation injury. Thus, SAN represents a therapeutic option for protecting against IR-induced intestinal injury in preclinical settings.
Jia-You FangTse-Hung HuangWei-Jhang ChenIbrahim A. Aljuffali...
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查看更多>>摘要：Rhubarb as an herbal medicine has been shown to exhibit antiadipogenic activity. This study evaluated and compared the lipid-lowering activity of five rhubarb hydroxyanthraquinones (HAQs), including chrysophanol, aloe emodin, emodin, physcion, and rhein, aiming to identify candidate compounds for obesity treatment. Examination of the antiobesity effects of HAQs in 3T3-L1 adipocytes and high-fat diet (HFD)-induced obese rats showed that these anthraquinone compounds inhibited lipid accumulation in 3T3-L1 cells before and after differentiation. Emodin and rhein showed greater inhibition than the other compounds; dosage at 50 μM reduced intracellular triglyceride (TG) by about 30% in the differentiated adipocytes. Both compounds also revealed lipolytic effects to increase glycerol release from adipocytes. Adipokine overexpression induced by differentiation was downregulated by emodin and rhein through mitogen-activated protein kinase (MAPK) signaling. Despite their structural similarity, emodin and rhein exhibited different mechanisms on adipogenesis and lipid metabolism. Rhein restrained lipid deposition by controlling adipogenic transcriptional factors and lipolytic li-pases during differentiation. The lipid-lowering effects of emodin did not use these pathways but reduced levels of lipogenic enzymes. HFD consumption in rats significantly increased body weight, visceral fat mass and adipocyte size, which were attenuated by intraperitoneal delivery of emodin or rhein. Rhein showed greater amelioration of obesity than emodin, decreasing plasma cholesterol by 29% and 14%, respectively. HAQs also suppressed cytokine upregulation in the liver and adipose tissues of obese rats. Rhein is a potential antiobesity agent through its ability to regulate obesity-associated adipogenesis, lipolysis and inflammation.
Mrunal D. BarbhaiMuzaffar HasanSneh PuniaSangram Dhumal...
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查看更多>>摘要：Huge quantities of byproducts/wastes generated in onion processing are usually discarded, but they are excellent sources of bioactive compounds and phytochemicals. However, with growing interest in the sustainable use of resources and the circular economy to reduce adverse impacts on the environment, food processing wastes such as onion peel/skin can be extracted and employed as inputs in developing or reformulating nutrient supplements, and pharmacological drugs. This review highlights major bioactive components, especially total phenolics, total flavonoid, quercetin and its derivatives present in onion peel/skin and their therapeutic applications as car-dioprotective, neuroprotective, antiobesity, antidiabetic, anticancer and antimicrobial agents. The present review emphasized that onion peel is one of the important agricultural by-products which is rich in bioactive compounds and can be utilized as health promoting ingredient especially in pharmacological and biomedical fields. Thus, with increasing burden of life style disorders/non-communicable diseases, finding suitable natural alternative for their treatment is one major concern of the researchers and onion peel and its extract can be exploited as a prime ingredient.
查看更多>>摘要：Atherosclerosis (AS) is a chronic inflammatory vascular disease with a multifactorial pathogenesis. It becomes a global health concern, especially causing an array of fatal consequences among the elderly. However, the mechanisms of AS remain unexplained. The transforming growth factor-β (TGF-β) signaling pathway is widely involved in the inflammation, immune function, proliferation, differentiation , and apoptosis in vivo. Based on previous researches, it has not been confirmed whether the TGF-β pathway promotes or inhibits atherosclerosis. Furthermore, more and more studies have found that microRNAs can regulate atherosclerosis through the TGF-β signaling pathway. In this review, we summarize and discuss the role of microRNAs in the pathogenesis of atherosclerosis via the TGF-β signaling pathway.
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