Role of Wnt signaling pathways in type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) has become a major global public health issue in the twenty-first century and its incidence has increased each year. Wnt signaling pathways are a set of multi-downstream signaling pathways activated by the binding of Wnt ligands to membrane protein receptors. Wnt signaling pathways regulate protein expression and play important roles in protecting the body's normal physiological metabolism. This review describes Wnt signaling pathways, and then aims to reveal how Wnt signaling pathways participate in the occurrence and development of T2DM. We found that Wnt/c-Jun N-terminal kinase signaling was closely associated with insulin resistance, inflammatory response, and pancreatic ß-cell and endothelial dysfunction. ß-catenin/transcription factor 7-like 2 (TCF7L2)-mediated and calcineurin/nuclear factor of activated T cells-mediated target genes were involved in insulin synthesis and secretion, insulin degradation, pancreatic ß-cell growth and regeneration, and functional application of pancreatic ß-cells. In addition, polymorphisms in the TCF7L2 gene could increase risk of T2DM according to previous and the most current results, and the T allele of its variants was a more adverse factor for abnormal pancreatic ß-cell function and impaired glucose tolerance in patients with T2DM. These findings indicate a strong correlation between Wnt signaling pathways and T2DM, particularly in terms of pancreatic islet dysfunction and insulin resistance, and new therapeutic targets for T2DM may be identified.

Simultaneous detection of the spike and nucleocapsid proteins from SARS-CoV-2 based on ultrasensitive single molecule assays.

Nucleic acid detection technology based on polymerase chain reaction (PCR) and antibody detection based on immunochromatography still have many problems such as false negatives for the diagnosis of coronavirus disease 2019 (COVID-19). Therefore, it is of great importance to develop new techniques to improve the diagnostic accuracy of COVID-19. We herein developed an ultrasensitive, rapid, and duplex digital enzyme-linked immunosorbent assay (dELISA) for simultaneous detection of spike (S-RBD) and nucleocapsid (N) proteins of SARS-CoV-2 based on a single molecule array. This assay effectively combines magnetic bead encoding technology and the ultrasensitive detection capability of a single molecule array. The detection strategies of S-RBD protein and N-protein exhibited wide response ranges of 0.34-1065 pg/mL and 0.183-338 pg/mL with detection limits of 20.6 fg/mL and 69.8 fg/mL, respectively. It is a highly specific method for the simultaneous detection of S-RBD protein and N-protein and has minimal interference from other blood proteins. Moreover, the spike assay showed a satisfactory and reproducible recovery rate for the detection of S-RBD protein and N-protein in serum samples. Overall, this work provides a highly sensitive method for the simultaneous detection of S-RBD protein and N-protein, which shows ultrasensitivity and high signal-to-noise ratio and contributes to improve the diagnosis accuracy of COVID-19.

Geographical discrimination of ethanol based on stable isotope ratio analysis coupled with statistical methods: The Chinese case study.

The demand for the effective traceability of hazardous chemicals is crucial for preventing and controlling chemical spills and other accidents involving hazardous chemicals. The aim of the study was to investigate the correlation between the geographical location of ethanol-producing industrial sites and the carbon, hydrogen, and oxygen stable isotope ratios of the Chinese-manufactured ethanol using statistical classification analysis to enable the traceability of the ethanol. The isotopic data of 54 ethanol samples obtained from 18 different ethanol manufacturing plants in China between 2019 and 2020. The results of the statistical analysis demonstrated that the δ18O values of the ethanol positively correlated with latitudes of the production plants but negatively correlated with the δ13C values of the ethanol. A small number of samples derived from sites that were geographically close to each other could not be visually distinguished by PCA and HCA. However, by applying and comparing the results of classification by LDA, K-NN and Ensemble, an optimal classification model was obtained. Upon application of these models, 96.3% of the ethanol samples were correctly classified based on their geographical origin, indicating that the combination of isotopic ratios and latitude data is practical and effective for measuring the traceability of ethanol.

Recombinant streptavidin fusion proteins as signal reporters in rapid test of human hepatitis C virus infection.

BACKGROUND: Early diagnosis of hepatitis C virus (HCV) infection is very important for the treatment of the disease. Development of sensitive and specific rapid detection assays is of great significance for the diagnosis. Here, we describe a promising method of using gold-labeled streptavidin fusion proteins as novel signal reporter in a rapid detection assay for HCV infection. METHODS: Recombinant genes encoding streptavidin fused with Escherichia coli maltose-binding protein (MBP) or with a portion of bacterial translational initiation factor 2 were cloned in expression vectors pMAL-5CX and pET28 and transformed in proper Escherichia coli host strains. The genes were induced and streptavidin fusion proteins, named M-STV and IF-STV, respectively, were purified by affinity chromatography to over 90% purity. The biotin-binding activity of M-STV and IF-STV was tested by enzyme-linked immunosorbent assay (ELISA). M-STV was labeled with colloidal gold nanoparticles and used as a signal reporter to develop a lateral flow-based rapid test for detecting anti-HCV antibodies in human blood samples. RESULTS: M-STV showed slightly higher biotin-binding activity and similar binding specificity as compared to commercial streptavidin. The gold-labeled M-STV bound specifically to biotin moieties immobilized on the rapid test strips in a dose-responsive manner and was successfully used in detecting HCV antibodies in serum samples of patients infected with HCV. The rapid test displayed higher detection sensitivity than gold-labeled commercial NeutrAvidin. CONCLUSION: Our results indicate that gold-labeled M-STV is a promising agent in rapid tests of HCV infection and possibly other viral infections.

Association between circulating antioxidants and sleep disorders: comprehensive results from NHANES 2017-2018.

Background: Oxidative stress plays an important role in the occurrence and pathological process of numerous human diseases. A bidirectional relationship was found between sleep disorders and oxidative stress. However, the association between circulating antioxidant levels and the risk of sleep disorders at the population-scale has yet to be determined. Methods: We used the dataset from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 data release cycle and included 3062 adult participants aged 25-75 years. The circulating antioxidants levels in serum were measured, and the sleep status was assessed by self-reported sleep disorder questionnaire tests. We investigated the association and exposure-response relationship between the 12 main circulating antioxidants and sleep disorders using a generalized additive model (GAM), multiple linear, binary logistic, and restricted cubic spline (RCS) regression models. Multiple sensitivity analyses were conducted to validate the results of our study. Results: Significantly lower serum concentrations of ten antioxidants were observed in the group which had trouble sleeping symptoms compared to the control group. After adjusting for all the covariates, the binary logistic regression models indicated that six of the circulating antioxidants including alpha-carotene, alpha-cryptoxanthin, trans-beta-carotene, beta-cryptoxanthin, lutein and zeaxanthin, and vitamin C, showed a significant association with the risk of overall trouble sleeping symptoms, with odds ratios corresponding to 0.88 (95% CI: 0.80-0.96), 0.74 (95% CI: 0.62-0.87), 0.87 (95% CI: 0.79-0.97), 0.85 (95% CI: 0.75-0.95), 0.72 (95% CI: 0.61-0.84), and 0.83 (95% CI: 0.74-0.93), respectively. The GAM and multiple linear regression revealed similar associations whereas the RCS regression models further confirmed their significant negative exposure-response relationship. Conclusions: The circulating carotenoids and vitamin C levels were negatively correlated with the risk of sleep disorders. Higher circulating antioxidant levels were significantly associated with a lower risk of sleep disorders. The potential health risk of low circulating antioxidants levels was higher in the female population than in the male population.

Anti-inflammatory effects of purple sweet potato anthocyanin extract in DSS-induced colitis: modulation of commensal bacteria and attenuated bacterial intestinal infection.

Purple sweet potato anthocyanins have been acknowledged for their beneficial effects on human inflammatory bowel diseases (IBD). Although the ability of anthocyanins in modulating the gut microbiota has been reported, the relationship between the bacteria modulated by anthocyanins and intestinal inflammation has not been fully elucidated. We aimed to ascertain whether the purple sweet potato anthocyanin extract (PSPAE) modulation of gut microbiota in the dextran sodium sulphate (DSS) induced chronic colitis mouse model could result in the maintenance of intestinal homeostasis and protection against bacterial intestinal inflammation. Chronic colitis was induced by adding DSS in drinking water while administering the mice with PSPAE via gavage (20 mg kg-1). Effects on colon tissue damage, gut microbiota composition, tight junction protein, and cytokines were evaluated. PSPAE prevented the loss of Bifidobacterium and Lactobacillus and inhibited the increase of Gammaproteobacteria and Helicobacter upon DSS treatment. The non-pathogenic-dependent and pathogenic-dependent microenvironments were established upon treatment with broad-spectrum antibiotics. Both PSPAE treatment and non-pathogenic treatments modified the colonic expression of mouse tight junction proteins and maintained the architecture of the colon. However, the non-pathogenic treatment could not attenuate intestinal inflammation. Moreover, the pathogenic-dependent dysbiosis was exacerbated because of the increasing colonization of pathogens such as Helicobacter. The PSPAE exerted the modulation of gut microbiota to maintain the gut microbiome homeostasis in DSS-induced chronic colitis mice, which may help to propose a new treatment that combines efficacy and reduction of the possibility of bacterial intestinal infection.

Combination of cyanidin-3-O-glucoside and cisplatin induces oxidative stress and apoptosis in HeLa cells by reducing activity of endogenous antioxidants, increasing bax/bcl-2 mRNA expression ratio, and downregulating Nrf2 expression.

Investigation on potentiation of existing drugs with natural compounds to enhance efficacy and reduce toxic effect of the drugs has been increasing in recent years. This paper reports cytotoxic effect (apoptosis-related and oxidative stress-related effect) of cyanidin-3-O-glucoside (C3G), cisplatin (DDP), and their combination (C3G-DDP) on cervical cancer HeLa cells. Concentration of intracellular reactive oxygen species (ROS) was determined by employing fluorescent marker 2',7'-dichlorodihydrofluorescein diacetate. On the other hand, malondialdehyde (MDA) and glutathione (GSH) concentration, and activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were quantitated by commercially available assay kits. C3G-DDP significantly inhibited the activity of SOD, CAT, and GSH-Px. Simultaneously, C3G-DDP reduced GSH concentration while increased the concentration of ROS and MDA. Moreover, Western blot analysis suggested that C3G-DDP significantly reduced the expression of nuclear factor erythroid 2-related factor-2 (Nrf2) and Nrf2 target proteins: heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1). In contrast, C3G-DDP increased the expression of Keap1. Furthermore, C3G-DDP significantly upregulated and downregulated the mRNA expressions of bax and bcl-2, respectively, thereby increasing bax/bcl-2 mRNA expression ratio. Overall, our findings propose that potentiation of DDP with C3G improves cancer cell susceptibility, specifically cervical cancer cells, to DDP. PRACTICAL APPLICATIONS: Cisplatin is recommended by most medical oncologists worldwide to treat cancer. Despite its neoplastic efficacy, it has undesirable side effects including nausea, vomiting, nephrotoxicity, and hepatotoxicity. Natural biologically active food ingredients are suggested to be used as antioxidants along with DDP therapy to prevent cisplatin-induced toxicity. C3G-DDP protected HeLa cells from oxidative stress by reducing NQO1 and HO-1 levels and regulated the Nrf2 signaling pathway. In addition, C3G-DDP protected HeLa cells from oxidative stress-induced apoptosis by increasing bcl-2 levels and decreasing bax levels. These results expanded our understanding of the role of C3G in a cervical cancer cell model, and provided a potential new treatment strategy for this cancer, as well as a theoretical basis for the development of new drugs in the future.

Assessment of myocardial function by two-dimensional speckle tracking echocardiography in patients with Kawasaki disease: a mid-term follow-up study.

BACKGROUND: Myocardial impairment proved by histological studies persists in late convalescent phase Kawasaki disease patients. Whether Kawasaki disease-induced myocardial lesions can be detected in an earlier time is not well explored. In this study, we aimed to evaluate left ventricular (LV) myocardial function by two dimensional speckle tracking echocardiography (2DSTE) in late convalescent phase Kawasaki disease patients. METHODS: A total of 68 Kawasaki disease patients during mid-term phase including 47 with no coronary artery aneurysm (NCAA) and 21 with coronary artery aneurysm (CAA), and 60 controls with age matched were consecutively enrolled. RESULTS: No significant differences on conventional echocardiographic LV systolic function indices were found among group comparison. Compared with controls, Kawasaki disease patients had lower global longitudinal stain (GLS) and global circumferential stain (GCS). In subgroup analysis, both those with CAA and without CAA had lower GLS, lower GCS, higher amino-terminal propeptide of type III procollagen (PIIINP) and higher carboxyterminal propeptide of procollagen type I (PIPC) than in controls. GLS had significantly negative correlations with PIIINP (r = -0.69, P = 0.002) and PIPC (r = -0.82, P = 0.000). CONCLUSION: Subclinical myocardial dysfunction in mid-term follow-up Kawasaki disease patients existed regardless of coronary artery status despite normal measurements of LV systolic function by routine echocardiography, and myocardial fibrosis may play a contributed role in this subclinical myocardial function impairment. 2DSTE is a valuable imaging modality for detecting regional and global myocardial dysfunction in Kawasaki disease patients in an early time.

Glucose-rich polysaccharide from dried 'Shixia' longan activates macrophages through Ca2+ and CR3- mediated MAPKs and PI3K-AKT pathways.

A water-soluble glucose-rich polysaccharide from dried 'Shixia' longan pulp (LPsx) has been isolated for the first time, and its structure and immuno-regulatory mechanism were studied. LPsx is a hetero-polysaccharide with the average molecular weight 4102 g/mol. It was mainly consisted of glucose (95.9%), and small proportions of arabinose (2.1%), galactose (1.0%), mannose (0.6%), and xylose (0.4%). As analyzed by NMR, LPsx was mainly composed of (1 â†’ 6)-α-d-glucose and (1 â†’ 6)-ß-d-glucose, branched with α-d-glucose-(1→. The immunomodulatory activity study showed that LPsx significantly increased the phagocytosis of macrophages, and strongly promoted the production of NO, IL-1ß, IL-6 and TNF-α. Moreover, LPsx could inhibit the inflammatory response induced by lipopolysaccharide. The immuno-regulatory mechanism of LPsx was studied using RNA- sequencing and receptors activity analyses. It was found that LPsx induced macrophage activation via Ca2+ and CR3-mediated MAPKs and PI3K-AKT signaling pathways. The results would be helpful for revealing the health promoting mechanism of dried 'Shixia' longan in traditional Chinese medicine.

The Efficacy of Fecal Microbiota Transplantation in Experimental Autoimmune Encephalomyelitis: Transcriptome and Gut Microbiota Profiling.

OBJECTIVE: To study the protective effect of fecal microbiota transplantation (FMT) on experimental autoimmune encephalomyelitis (EAE) and reveal its potential intestinal microflora-dependent mechanism through analyses of the intestinal microbiota and spinal cord transcriptome in mice. METHOD: We measured the severity of disease by clinical EAE scores and H&E staining. Gut microbiota alteration in the gut and differentially expressed genes (DEGs) in the spinal cord were analyzed through 16S rRNA and transcriptome sequencing. Finally, we analyzed associations between the relative abundance of intestinal microbiota constituents and DEGs. RESULTS: We observed that clinical EAE scores were lower in the EAE+FMT group than in the EAE group. Meanwhile, mice in the EAE+FMT group also had a lower number of infiltrating cells. The results of 16S rRNA sequence analysis showed that FMT increased the relative abundance of Firmicutes and Proteobacteria and reduced the abundance of Bacteroides and Actinobacteria. Meanwhile, FMT could modulate gut microbiota balance, especially via increasing the relative abundance of g_Adlercreutzia, g_Sutterella, g_Prevotella_9, and g_Tyzzerella_3 and decreasing the relative abundance of g_Turicibacter. Next, we analyzed the transcriptome of mouse spinal cord tissue and found that 1476 genes were differentially expressed between the EAE and FMT groups. The analysis of these genes showed that FMT mainly participated in the inflammatory response. Correlation analysis between gut microbes and transcriptome revealed that the relative abundance of Adlercreutzia was correlated with the expression of inflammation-related genes negatively, including Casp6, IL1RL2 (IL-36R), IL-17RA, TNF, CCL3, CCR5, and CCL8, and correlated with the expression of neuroprotection-related genes positively, including Snap25, Edil3, Nrn1, Cpeb3, and Gpr37. CONCLUSION: Altogether, FMT may selectively regulate gene expression to improve inflammation and maintain the stability of the intestinal environment in a gut microbiota-dependent manner.

Cyanidin-3-O-glucoside and cisplatin inhibit proliferation and downregulate the PI3K/AKT/mTOR pathway in cervical cancer cells.

Natural compounds have been increasingly investigated as substances enhancing the effect of drugs and reducing drug-related adverse reactions. The objective of this study was to determine how a combination of cisplatin (DDP) with cyanidin-3-O-glucoside (C3G) affected malignancy features of cervical cancer cells. The results demonstrated that the proliferation of HeLa cells treated with 5 µg/ml DDP, 400 µg/ml C3G, or a combination of both (5 µg/ml DDP and 400 µg/ml C3G) was inhibited by 17.43%, 34.98%, and 63.38%, respectively. The IC50 values for DDP and the DDP/C3G combination treatments in HeLa cells were 18.53 and 6.435 µg/ml, respectively. Flow cytometry analysis indicated that treatment with DDP, C3G, or the combination induced G1 cell cycle arrest and apoptosis in HeLa cells. Furthermore, after treatment, cyclin D1 and Bcl-2 levels decreased; Bax, cleaved caspase-3, p53, and TIMP-1 were activated; and the PI3K/AKT/mTOR signaling pathway was modulated. These anticancer effects were enhanced in cells treated with the combination of DDP and C3G compared to those treated with DDP or C3G alone. Our study indicates that C3G increases the antitumor activity of DDP, suggesting a potential strategy to reduce adverse effects associated with chemotherapy in cervical cancer. PRACTICAL APPLICATION: Natural biologically active food ingredients are suggested to have a potential to enhance the effect of chemotherapy in cancer. We believe that our study makes a significant contribution to the literature because it revealed, for the first time, that C3G could increase the antitumor activity of DDP, suggesting a potential strategy to reduce adverse effects associated with chemotherapy in cervical cancer.

Beneficial effects of Aronia melanocarpa berry extract on hepatic insulin resistance in type 2 diabetes mellitus rats.

We aimed to investigate) the effects of Aronia melanocarpa berry extract (AMBE) on hepatic insulin resistance and its mechanism at the molecular level in high-fat diet (HFD)- and streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) rats. The rats were supplemented with AMBE at doses of 100 and 400 mg/kg body weight (bw) daily for 8 weeks. AMBE significantly reduced blood glucose and serum insulin levels and the homeostatic model assessment for insulin resistance score; improved glucose tolerance; increased hepatic glycogen content; and regulated glucose metabolism enzyme activity, including glucokinase, pyruvate kinase, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase in the liver. AMBE also reduced lipid accumulation and oxidative stress along with inflammation in the hepatic tissue of T2DM rats and improved hepatic function. The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was activated by AMBE through the elevation of insulin receptor substrate-2, PI3K, Akt, and glycogen synthase kinase-3ß phosphorylation and glucose transporter 2, which might contribute to the promotion of glycogen synthesis and improvement of hepatic insulin resistance. AMBE shows promise as an ingredient of functional foods for alleviating hepatic insulin resistance in T2DM. PRACTICAL APPLICATION: The extract from the berries of Aronia melanocarpa (Michx.) Elliott (AMBE), with its relatively high content of polyphenolic compounds, has been shown to exert hypoglycemic effects in animal models of diabetes. Our findings support the use of A. melanocarpa as a functional food additive for the alleviation of hepatic insulin resistance and the management of glucose homeostasis in T2DM.

Left ventricular systolic dyssynchrony in patients with Kawasaki disease: a real-time three-dimensional echocardiography study.

The left ventricular (LV) systolic dyssynchrony index (SDI) is an important prognostic indicator for many cardiovascular diseases; however, the characteristics of the SDI in patients with Kawasaki disease (KD) are unknown. In this study, we aimed to identify and quantify the SDI using real-time three-dimensional echocardiography (RT3DE) in KD patients during different phases. In addition, we intended to explore whether the SDI is associated with systolic dysfunction. Seventy consecutive KD patients and seventy age- and sex-matched controls were enrolled. The SDIs (percent of cardiac cycle) of 16 segments (16-SDI%) and 12 segments (12-SDI%) were calculated based on the defined standard deviation of each segment time from end diastole to the minimal systolic volume according to the 17-segment model (apex excluded). In the acute phase, the 16-SDI% and 12-SDI% were significantly higher in KD patients than in controls (4.40 ± 0.14 vs. 1.98 ± 0.12, P = 0.000; 3.55 ± 1.21 vs. 1.67 ± 0.93, P = 0.009, respectively), and patients with coronary artery aneurysm (CAA) exhibited higher 16-SDI% (P = 0.021) and 12-SDI% (P = 0.034) than patients without CAA. In the convalescent phase, patients with CAA still had higher 16-SDI% (P = 0.002) and 12-SDI% (P = 0.031) than controls, while the SDI in patients without CAA recovered to normal. The 16-SDI% was negatively correlated with the LV ejection fraction obtained from RT3DE (r = - 0.845, P = 0.000). Mechanical dyssynchrony is prevalent in KD patients during the acute phase and transient in patients without CAA, while patients with CAA still have impaired synchrony even in the convalescent phase. LV systolic dysfunction is associated with increased dyssynchrony. RT3DE is a valuable modality for identifying and quantifying dyssynchrony in KD patients.

Abnormal fear circuits activities correlated to physical symptoms in somatic anxiety patients.

BACKGROUND: Somatic anxiety patients complain of physical symptoms and exhibit repeated checking behavior. Overgeneralization of fear is a characteristic of anxiety disorders. However, the role of fear in the somatic anxiety patients remains unclear. We hypothesized that somatic anxiety patients have abnormal fear circuits, including the amygdala, hippocampus, thalamus, orbitofrontal cortex and anterior cingulate cortex, which can aggravate physical symptoms. METHODS: 33 anxiety patients and 25 healthy controls (HCs) were recruited. The severity of the anxiety and somatic symptoms was assessed with the Hamilton anxiety scale and the 15-item somatic symptom severity scale from the Patient Health Questionnaire (PHQ-15). The amplitude of low-frequency fluctuations (ALFF) in resting-state functional magnetic resonance imaging was used to assess abnormalities in the fear circuit. We compared the ALFF between patients and HCs with respect to the fear circuit and conducted correlation analysis to investigate the relationship between somatic symptoms and the ALFF in abnormal cerebral regions. RESULTS: The ALFF of the left thalamus and left hippocampus was significantly higher in the patient group than the HC group, and was positively correlated with the PHQ-15 values. LIMITATIONS: We did not divide the patient group into drug treated or drug free in our subgroup analysis. There was a lack of the paradigm to test the generalization of fear for patients in this study. Furthermore, the small sample size may have affected the results. CONCLUSION: Somatic symptoms in patients with anxiety are related to abnormal fear circuits, whose degree of abnormality is associated with symptom severity.

Structural characterization and immunomodulatory activity of a water-soluble polysaccharide from Ganoderma leucocontextum fruiting bodies.

Ganoderma leucocontextum is a new species of Ganoderma discovered in 2014. Up to now, the structural characteristics and immunoregulatory activity of its polysaccharides remain virtually unknown. In this study, a water-soluble polysaccharide termed, GLP-3, was purified from G. leucocontextum by ultrafiltration and column chromatography. The results revealed that GLP-3 mainly consisted of glucose (92.7 %) and its weight average molecular weight was 159.7 kDa. The structural analysis indicated that the backbone of GLP-3 was →4)-α-D-Glcp-(1→4,6)-ß-D-Glcp-(1→ with a ß-Glcp-(1→ branch. Atomic force microscopy and Congo red experiments revealed that GLP-3 might possess a globular structure with triple-helix conformation in water. Moreover, GLP-3 was recognized by toll-like receptor 2 (TLR2) and exerted immunomodulatory effects via activating mitogen-activated protein kinases (MAPKs), phosphatidylinositol-3-kinase (PI3K)/Akt and nuclear factor-κB (NF-κB) signaling pathways in RAW 264.7 macrophages. Collectively, these results suggested that GLP-3 could be developed as a potential functional food ingredient for immunomodulation.

Preparation, physicochemical characterization, and anti-proliferation of selenium nanoparticles stabilized by Polyporus umbellatus polysaccharide.

Selenium nanoparticles (SeNPs), a novel selenium form, have attracted worldwide attention due to their bioactivities and low toxicity. This study aimed to assess the physicochemical characterization, storage stability, and anti-proliferative activities of SeNPs stabilized by Polyporus umbellatus polysaccharide (PUP). Results showed that orange-red, zero-valent, amorphous and spherical SeNPs with mean diameter of approximately 82.5 nm were successfully prepared by using PUP as a capping agent. PUP-SeNPs solution stored at 4 °C in dark condition could be stable for at least 84 days. Moreover, PUP-SeNPs treatment inhibited four cancer cell lines proliferation in a dose-dependent manner, while no significant cytotoxicity towards three normal cell lines was observed. Comparing with the other cancer cell lines (HepG2, Hela, and HT29), PUP-SeNPs displayed the most sensitive towards MDA-MB-231 cells with an IC50 value of 6.27 µM. Furthermore, PUP-SeNPs significantly up-regulated Bax/Bcl-2 ratio, promoted cytochrome c release, increased caspase-9, -8 and -3 activities, and poly (ADP-ribose) polymerase cleavage, suggesting that mitochondria-mediated and death receptor-mediated apoptotic pathways were activated in MDA-MB-231 cells. Besides, PUP-SeNPs possessed better anti-proliferative activity than selenomethionine as well as lower cytotoxicity than sodium selenite. Taken together, PUP-SeNPs have strong potential as a dietary supplement for application in cancer chemoprevention, especially breast cancer.

Increased connective tissue growth factor expression in a rat model of chronic heart allograft rejection.

BACKGROUND/PURPOSE: Chronic rejection limits the long-term success of cardiac transplantation and the underlying cause of the disease is unknown. Connective tissue growth factor (CTGF) is considered as a mitogenic and chemotactic factor for fibroblasts, and is associated with cell proliferation and collagen synthesis. We evaluated the expression of CTGF in a rat model of heart allograft chronic rejection. METHODS: Intra-abdominal heterotopic heart transplantation was performed from 20 Wistar rats to 20 Sprague-Dawley (SD) rats that received cyclosporine, mycophenolate mofetil and methylprednisolone as immunosuppression. Ten heart allografts were explanted at 2 and 8 weeks postoperatively for analysis of morphologic changes. The hearts from 10 normal Wistar rats served as a control group. Coronary artery density, luminal loss of myocardial coronary arteries, and myocardial fibrosis were measured. The expression of CTGF was studied by immunohistochemistry. Correlation between CTGF expression and development of cardiac allograft vasculopathy (CAV) or fibrosis was studied. RESULTS: Allografts harvested at 8 weeks postoperatively showed more coronary intimal proliferation, fibrosis and CTGF expression compared with the 2-week allografts (p < 0.05) and the controls (p < 0.01), but the coronary artery density was lower than in the control group (p < 0.05). However, the control group showed negligible CTGF expression. There were strong negative correlations between the gray value of CTGF protein expression and cardiac fibrosis and coronary intimal occlusion (r = -0.734, -0.713; p < 0.01), which demonstrated that CTGF protein expression was positively correlated with cardiac fibrosis and coronary intimal occlusion. CONCLUSION: CTGF is expressed in cardiomyocytes in CAV. Increased expression of CTGF in cardiac allografts is associated with development of CAV and fibrosis formation.

Anti-inflammatory and immunosuppressive effect of phloretin.

This study investigated the effect of phloretin (Ph) on the proliferation, activation, and cell-cycle distribution of mouse T lymphocytes and NO production and phagocytosis of macrophages. Carboxyfluorescein diacetatesuccinimidyl ester (CFDA-SE) staining plus flow cytometry assay was employed to obtain the proliferation-related index (PI) of lymphocytes. The expression levels of CD69 and CD25 on T lymphocytes stimulated with Con A were evaluated with flow cytometry after staining with fluorescent monoclonal antibody. Cell-cycle distribution of T lymphocytes was analyzed by propidium iodide staining. Griess kit was used to evaluate the NO production and fluorescent microbeads were used to analyze the phagocytosis ability of macrophages. Our results showed that phloretin (40, 60, and 80 micromol x L(-7)) significantly inhibited the proliferation of T lymphocytes and the PI reduced from 1.41 +/- 0.13 to 1.34 +/- 0.16, 1.19 +/- 0.12 and 1.07 +/- 0.06, respectively. Phloretin significantly inhibited the expression of CD69 and CD25 (P < 0.01). The cell cycle distribution analysis showed that phloretin could induce a cell cycle arrest at G0/G1 phase. NO production of LPS +IFN-gamma group of macrophages was (26.72 +/- 3.57) micromol x L(-1), and was significantly reduced by phloretin (P < 0.01). And phagocytosis rate of macrophages was significantly reduced by phloretin (P < 0.01). The results demonstrate that phloretin might be developed into a new immuosuppressive drug.

Synergistic Effects of Aluminum Diethylphosphinate and Melamine on Improving the Flame Retardancy of Phenolic Resin.

A series of novel flame retardants (aluminum diethylphosphinate and melamine) were used to improve the fire performance of phenolic resin. Fourier transform infrared spectroscopy (FTIR) was used to characterize the modification results. Thermo-gravimetric analysis (TGA) was used to study the thermal decomposition of phenolic resin system, and the flame retardancy of phenolic resin system was tested by vertical combustion test (UL-94) and limiting oxygen index (LOI). The combustion properties of modified phenolic resin were further tested with a cone calorimeter(CCT). Finally, the structure of carbon residue layer was measured by scanning electron microscopy (SEM). The results show that with the introduction of 10 wt % aluminum diethylphosphinate in phenolic resin, the LOI reaches 33.1%, residual carbon content increase to 55%. The heat release rate (HRR) decreased to 245.6 kW/m2, and the total heat release (THR) decreased to 58.6 MJ/m2. By adding 10 wt % aluminum diethylphosphinate and 3 wt % melamine, the flame retardancy of the modified resin can pass UL-94 V-0 flame retardant grade, LOI reaches 34.6%, residual carbon content increase to 59.5%. The HRR decreases to 196.2 kW/m2 at 196 s, relatively pure phenolic resin decreased by 35.5%, and THR decreased to 51 MJ/m2. Compared with pure phenolic resin, the heat release rate and total heat release of modified phenolic resin decreased significantly. This suggests that aluminum diethylphosphinate and melamine play a nitrogen-phosphorus synergistic effect in the phenolic resin, which improves the thermal stability and flame retardancy of the phenolic resin.

Thermal Decomposition Mechanism and Kinetics Study of Plastic Waste Chlorinated Polyvinyl Chloride.

Chlorinated polyvinyl chloride (CPVC), as a new type of engineering plastic waste, has been used widely due to its good heat resistance, mechanical properties and corrosion resistance, while it has become an important part of solid waste. The pyrolysis behaviors of CPVC waste were analyzed based on thermogravimetric experiments to explore its reaction mechanism. Compared with polyvinyl chloride (PVC) pyrolysis, CPVC pyrolysis mechanism was divided into two stages and speculated to be dominated by the dehydrochlorination and cyclization/aromatization processes. A common model-free method, Flynn-Wall-Ozawa method, was applied to estimate the activation energy values at different conversion rates. Meanwhile, a typical model-fitting method, Coats-Redfern method, was used to predict the possible reaction model by the comparison of activation energy obtained from model-free method, thereby the first order reaction-order model and fourth order reaction-order model were established corresponding to these two stages. Eventually, based on the initial kinetic parameter values computed by model-free method and reaction model established by model-fitting method, kinetic parameters were optimized by Shuffled Complex Evolution algorithm and further applied to predict the CPVC pyrolysis behaviors during the whole temperature range.