Extraction of functional natural products employing microwave-assisted aqueous two-phase system: application to anthocyanins extraction from mulberry fruits.

Aqueous two-phase extraction (ATPE) has been extensively utilized for the extraction and separation of tiny-molecule substances as a new system (system with short-chain ethanol and inorganic salts). In this study, an innovative method of extracting anthocyanins from mulberry was developed, employing microwave-assisted extraction with ethanol/ammonium sulfate as a biphasic extractant. Response surface methodology (RSM) was utilized to optimize anthocyanin extraction conditions: 39% ethanol (w/w), 13% ammonium sulfate (w/w), and liquid-to-solid ratio of 45:1, microwave duration 3 min, microwave temperature 32 °C, and microwave power 480 Watt (W). High-performance liquid chromatography (HPLC) analysis demonstrated no significant differences in the structure of mulberry anthocyanins before and after MAATPE treatment, furthermore. The extraction behavior of MAATPE was due to hydrogen bonding, according to Fourier transform infrared spectroscopy (FT-IR). Scanning electron microscopy analysis found that MAATPE damaged the cell structure via a microwave enhancement effect, which was more favorable to anthocyanin dissolution than standard extraction methods. The DPPH free radical scavenging rate of mulberry extracts at 0.5 mg/mL was higher than that of vitamin C (96.4 ± 0.76%), and the ABTS free radical scavenging rate (82.52 ± 2.13%) was close to that of vitamin C, indicating that MAATPE-derived mulberry extracts have good antioxidant activity.

Urantide alleviates atherosclerosis-related liver and kidney injury via the Wnt/ß-catenin signaling pathway in ApoE(-/-) mice.

OBJECTIVE: To investigate the role of urantide in the prevention and treatment of atherosclerosis (AS)-related liver and kidney injury by antagonizing the urotensin II/urotensin receptor (UII/UT) system and regulating the Wnt/ß-catenin signaling pathway. METHODS: Atherosclerotic ApoE-/- mice were treated with 20 mg/kg, 30 mg/kg, and 40 mg/kg urantide for 14 days. RESULTS: When ApoE-/- mice developed AS, significant pathological changes occurred in the liver and kidney, and the UII/UT system in tissue was highly activated; furthermore, the Wnt/ß-catenin signalling pathway was activated, and proteins related to this signalling pathway, such as GSK-3ß, AXIN2, CK­1, and APC, were significantly downregulated. After urantide treatment, the pathological damage to the liver and kidney was effectively improved, the activity of the UII/UT system was effectively inhibited, and the expression of the Wnt/ß-catenin signalling pathway and related proteins was restored. Wnt/ß-catenin signals were mainly localized in the cytoplasm, renal tubules, and interstitium. CONCLUSION: Urantide could improve AS-related liver and kidney injury by antagonizing the UII/UT system, and the improvements in liver and kidney function in atherosclerotic ApoE-/- mice may be related to inhibition of the Wnt/ß-catenin signalling pathway.

G-CSF reduces loss of dopaminergic neurons by inhibiting TNF-α and IL-1ß in mouse model of Parkinson's disease.

PURPOSE OF THE STUDY: granulocyte-colony stimulating factor (G-CSF) is a hematopoietic growth factor existing in neutrophils, glial cells and neurons. Increasing researches discovered that G-CSF improved cell survival in neurodegenerative diseases by its anti-inflammatory effect. However, the effect of G-CSF in suppressing inflammation in Parkinson's disease (PD) remains unclear. Thus, the purpose of this study is to explored the anti-inflammatory effect of G-CSF in mouse model of PD. MATERIALS AND METHODS: G-CSF was administrated in the PD model induced by MPTP. Subsequently, the protein of tyrosine hydroxylase (TH), ionized calcium-binding adaptor molecule 1 (Iba-1) and the inflammatory cytokines including tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß) in the midbrain were examined. In addition, the phosphorylated mitogen-activated protein kinases (MAPK) including c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38 MAPK in the midbrain were investigated. RESULTS: Compared with the MPTP group, the protein of TH in the midbrain was increased, while the Iba-1 and the inflammatory factors were decreased. In addition, the expression of phosphorylated JNK (p-JNK) in the midbrain of the MPTP + G-CSF group was decreased, while the phosphorylated ERK (p-ERK) levels were elevated. CONCLUSIONS: These findings emphasize that G-CSF inhibited the degradation of DA neurons. The protective effect is associated with the reduction of the inflammatory factors caused by the inhibition of the microglial activation. Moreover, G-CSF may decrease the inflammatory factors through the decrease of P-JNK and the increase of P-ERK.

Urotensin receptor antagonist urantide improves atherosclerosis-related kidney injury by inhibiting JAK2/STAT3 signaling pathway in rats.

OBJECTIVE: To investigate the role of urantide in the prevention and treatment of atherosclerotic nephropathy by antagonizing the urotensin II/urotensin receptor (UII/UT) system and regulating JAK2/STAT3 signaling pathway. METHODS: Atherosclerosis (AS) rats were treated with urantide at a concentration of 30 µg/kg for 3, 7, 14 days. RESULTS: An excessive expression of UII and its receptor G protein-coupled receptor 14 (GPR14) was seen in AS rat kidneys and the expression was significantly reduced after urantide administration. Either body weight, renal functions of urea nitrogen, urine proteins and anion gaps or expression of kidney injury-related genes Agtr1α, Nox4, Cyba and Ncf1 were improved after AS rats were treated with urantide. After antagonizing the UII/GPR14 system by using urantide, the expression of genes and proteins in the JAK2/STAT3 and ERK pathways was decreased, and the nuclear protein p-STAT3 and p-ERK were obviously decreased. p-JAK2 and p-STAT3 were decreased in the urantide group in a time-dependent manner. The UII/GPR14 system and JAK2/STAT3 signals were localized in tubules and then glomeruli to affect renal reabsorption and filtration. CONCLUSION: Urantide can effectively block the UII/GPR14 system by regulating the JAK2/STAT3 signaling pathway to prevent and treat atherosclerosis-related kidney injury. At this stage, effective inhibition of inflammatory signaling pathways is of great significance in the treatment of atherosclerosis.

Bending effect on the resistive switching behavior of a NiO/TiO2 p-n heterojunction.

Herein, NiO/TiO2 heterojunctions were fabricated by sol-gel spin coating on plastic substrates to investigate the effects of bending on resistive switching. The switching mechanism is well explained by the formation and rupture of oxygen-vacancy conducting filaments modulated by the p-n interface. Compared with that of the unbent film, the device ON/OFF ratio is slightly improved after 5000 bending repetitions. Finite element calculations indicate that the tensile stress of 0.79% can lead to the formation of channel cracks. Further charge transport analysis shows that the conducting filaments may cause an incomplete rupture because the bending-induced channel crack permeates through the p-n interface and reduces the local depletion-region width.

Role of rat autologous skin fibroblasts and mechanism underlying the repair of depressed scars.

The aim of the present study was to provide reliable experimental evidence for the application of autologous skin fibroblasts (asFbs) in the repair of depressed scars. In the experiments, depressed trauma was induced in male Wistar rats, and fibroblasts were separated from the removed skin tissues to culture in medium. In vitro cultured asFbs were injected into the depressed scar sites of rats, and the repair function of asFbs in the depressed scars was then examined at the cellular and whole-animal levels. The expression levels of type I and type III collagen in the dermal layer of the skin injected with asFb cells were significantly higher, as compared with those of the control, and type I collagen expression was significantly higher compared with Type III. Re-injection of asFbs into the dermal layer of depressed scars can markedly improve their repair. These results may prove useful for skin repair in clinical settings.

Activation of RAS/ERK alone is insufficient to inhibit RXRα function and deplete retinoic acid in hepatocytes.

Activation of RAS/ERK signaling pathway, depletion of retinoid, and phosphorylation of retinoid X receptor alpha (RXRα) are frequent events found in liver tumors and thought to play important roles in hepatic tumorigenesis. However, the relationships among them still remained to be elucidated. By exploring the transgenic mouse model of hepatic tumorigenesis induced by liver-specific expression of H-ras12V oncogene, the activation of RAS/ERK, the mRNA expression levels of retinoid metabolism-related genes, the contents of retinoid metabolites, and phosphorylation of RXRα were determined. RAS/ERK signaling pathway was gradually and significantly activated in hepatic tumor adjacent normal liver tissues (P) and hepatic tumor tissues (T) of H-ras12V transgenic mice compared with normal liver tissues (Wt) of wild type mice. On the contrary, the mRNA expression levels of retinoid metabolism-related genes were significantly reduced in P and T compared with Wt. Interestingly, the retinoid metabolites 9-cis-retinoic acid (9cRA) and all-trans-retinoic acid (atRA), the well known ligands for nuclear transcription factor RXR and retinoic acid receptor (RAR), were significantly decreased only in T compared with Wt and P, although the oxidized polar metabolite of atRA, 4-keto-all-trans-retinoic-acid (4-keto-RA) was significantly decreased in both P and T compared with Wt. To our surprise, the functions of RXRα were significantly blocked only in T compared with Wt and P. Namely, the total protein levels of RXRα were significantly reduced and the phosphorylation levels of RXRα were significantly increased only in T compared with Wt and P. Treatment of H-ras12V transgenic mice at 5-week-old or 5-month-old with atRA had no effect on the prevention of tumorigenesis or cure of developed nodules in liver. These events imply that the depletion of 9cRA and atRA and the inhibition of RXRα function in hepatic tumors involve more complex mechanisms besides the activation of RAS/ERK pathway.

Aberrant promoter methylation of p15 (INK4b) and p16 (INK4a) genes may contribute to the pathogenesis of multiple myeloma: a meta-analysis.

We carried out the current meta-analysis aiming to comprehensively assess the potential role of p15 (INK4b) and p16 (INK4a) aberrant promoter methylation in the pathogenesis of multiple myeloma (MM). The MEDLINE (1966 ~ 2013), Cochrane Library (Issue 12, 2013), EMBASE (1980 ~ 2013), CINAHL (1982 ~ 2013), Web of Science (1945 ~ 2013), and Chinese Biomedical (CBM) (1982 ~ 2013) databases were searched without language restrictions. Meta-analyses were conducted using Stata software (Version 12.0, Stata Corporation, College Station, TX, USA). Odds ratios (ORs) and their 95 % confidence intervals (95 %CIs) were calculated. Thirteen clinical case-control studies, which enrolled a total of 465 MM patients and 180 healthy subjects, were included in the meta-analysis. The results of our meta-analysis demonstrated that the frequencies of p15 (INK4b) and p16 (INK4a) promoter methylation in cancer samples were significantly higher than in normal samples (p15 (INK4b) : OR = 6.26, 95 %CI = 3.87 ~ 10.12, P < 0.001; p16 (INK4a) : OR = 2.26, 95 %CI = 1.22 ~ 4.20, P < 0.001). Ethnicity-stratified analysis showed that the aberrant methylation of p15 (INK4b) was significantly related with the risk of MM among both Caucasians and Asians (all P < 0.05). Furthermore, our results also illustrated a strong positive correlation between p16 (INK4a) promoter methylation and the pathogenesis of MM among Asians (OR = 5.17, 95 %CI = 3.45 ~ 7.74, P < 0.001), but not among Caucasians (P > 0.05). The current meta-analysis confirms and reinforces existing findings that p15 (INK4b) and p16 (INK4a) promoter methylation may be closely implicated in the pathogenesis of MM.