Search

This study is aimed at exploring the release of bound polyphenols (BP) from insoluble dietary fiber (IDF) and its mechanism by solid-state fermentation (SSF) via Trichoderma viride. The results indicated that BP released by SSF (5.55 mg GAE/g DW) was significantly higher than by alkaline hydrolysis. In addition, 39 polyphenols and catabolites were detected, and the related biotransformation pathways were speculated. Quantitative analysis showed that SSF released more ferulic acid, p-coumaric acid, and organic acids, which led to advances in antioxidant, α-amylase, and α-glucosidase inhibitory activities. Furthermore, structural characteristics (scanning electron microscopy, X-ray diffraction, thermos gravimetric analysis, and Fourier transform infrared spectroscopy) and dynamic changes of carbohydrate-hydrolyzing enzymes indicated that the destruction of hemicellulose and the secretion of xylanase were vital for releasing BP. Overall, this study demonstrated that SSF was beneficial to release BP from IDF, which could provide insight into utilizing agricultural byproducts in a more natural and economical way.

The liver is a key player for maintaining glucose homeostasis. Excessive hepatic glucose production is considered to be a key for the onset of type 2 diabetes. The primary function of heme oxygenase-1 (HO1) is to catalyze the degradation of heme into biliverdin, ferrous iron, and carbon monoxide. Previous studies have demonstrated that the degradation of heme by HO1 in the liver results in mitochondrial dysfunction and drives insulin resistance. In this study, by overexpressing HO1 in hepatocytes and mice, we showed that HO1 promotes gluconeogenesis in a Foxo1-dependent manner. Importantly, HO1 overexpression increased the generation of ferrous iron in the liver, which further activates nuclear factor-κB and phosphorylates Foxo1 at Ser273 to enhance gluconeogenesis. We further assessed the role of HO1 in insulin-resistant liver-specific knockout of IRS1 and IRS2 genes (L-DKO) mice, which exhibit upregulation of HO1 in the liver and hepatic ferrous iron overload. HO1 knockdown by shRNA or treatment of iron chelator rescued the aberrant gluconeogenesis in L-DKO mice. In addition, we found that systemic iron overload promotes gluconeogenesis by activating the hepatic protein kinase A→Foxo1 axis. Thus, our results demonstrate the role of HO1 in regulating hepatic iron status and Foxo1 to control gluconeogenesis and blood glucose.

The major aim of the present study was to determine the effects of quercetin, a well-known flavonoid, on attenuating cisplatin (CDDP)-induced fat loss and the possible mechanisms. Tumor-bearing nude mice and tumor-free BALB/c mice were administrated with CDDP alone or in combination with quercetin by a diet containing 0.1% or 1% quercetin (LQ or HQ) or by intraperitoneal injection (IQ) to determine the effects of quercetin on the anticancer effect of CDDP or CDDP-induced fat loss. The effects of quercetin on fat accumulation in CDDP-exposed 3T3-L1 cells were also determined. We first showed that HQ and IQ significantly enhanced the anticancer effect of CDDP by upregulating p53- and p21-associated pathways, while tended to attenuate CDDP-induced fat loss in tumor-bearing nude mice. The study in 3T3-L1 cells showed that CDDP decreased the fat accumulation accompanied by strong upregulation of the expression of six genes which are associated with fat metabolism, while quercetin completely suppressed such an effect. The tumor-free BALB/c mice study consistently showed a protective effect of HQ on CDDP-induced body weight and epididymal fat loss. HQ also increased the fat levels in liver and muscle tissues. In epididymal fat tissues, HQ consistently attenuated CDDP-induced changes in fat metabolism-associated gene expression. However, CDDP alone or in combination with HQ did not affect the food intake. This study demonstrates that quercetin possesses the potential to suppress CDDP-induced fat loss may partly through the regulation of the fat metabolism-associated gene expression.

Food protein-derived bioactive peptides, particularly antihypertensive peptides, are important constituents of functional foods or nutraceuticals. Most antihypertensive are identified as the inhibitors of angiotensin converting enzyme (ACE), a key enzyme responsible for the generation of angiotensin II (Ang II), which is a vasoconstricting peptide. Hence, ACE has long been used as a universal target to identify antihypertensive peptides. Angiotensin converting enzyme 2 (ACE2), is a homolog of ACE but uses Ang II as its key substrate to produce angiotensin (1-7), exerting vasodilatory activity via the mas receptor (MasR). Therefore, ACE2 functions in the opposite way as ACE and is an emerging novel target for cardiovascular therapy. The potential of food protein-derived bioactive peptides in targeting ACE2 has been rarely explored. While, recently we found that IRW, an egg white ovotransferrin-derived antihypertensive peptide, reduced blood pressure in spontaneously hypertensive rats via the ACE2/Ang (1-7)/MasR axis, indicating a new mechanism of food protein-derived bioactive peptides in reducing blood pressure. The objectives of this review are to summarize the functions of the ACE2/Ang (1-7)/MasR axis and to examine its potential roles in the actions of food protein-derived antihypertensive peptides. The interaction between antihypertensive peptides and the ACE2/Ang (1-7)/MasR axis will also be discussed.

Oxidative stress is an important contributing factor for inflammation. Piper methysticum, also known as Kava-kava, is a shrub whose root extract has been consumed as a drink by the pacific islanders for a long time. Flavokawain A (FKA) is a novel chalcone derived from the kava plant that is known to have medicinal properties. This study was aimed at demonstrating the antioxidant molecular mechanisms mediated by FKA on lipopolysaccharide- (LPS-) induced inflammation in BALB/c mouse-derived primary splenocytes. In vitro data show that the nontoxic concentrations of FKA (2-30 μM) significantly suppressed the proinflammatory cytokine (TNF-α, IL-1β, and IL-6) release but induced the secretion of interleukin-10 (IL-10), an anti-inflammatory cytokine. It was also shown that FKA pretreatment significantly downregulated the LPS-induced ROS production and blocked the activation of the NFκB (p65) pathway leading to the significant suppression of iNOS, COX-2, TNF-α, and IL-1β protein expressions. Notably, FKA favored the nuclear translocation of Nrf2 leading to the downstream expression of antioxidant proteins HO-1, NQO-1, and γ-GCLC via the Nrf2/ARE signaling pathway signifying the FKA’s potent antioxidant mechanism in these cells. Supporting the in vitro data, the ex vivo data obtained from primary splenocytes derived from the FKA-preadministered BALB/c mice (orally) show that FKA significantly suppressed the proinflammatory cytokine (TNF-α, IL-1β, and IL-6) secretion in control-, LPS-, or Concanavalin A- (Con A-) stimulated cells. A significant decrease in the ratios of pro- and anti-inflammatory cytokines (IL-6/IL-10; TNF-α/IL-10) showed that FKA possesses strong anti-inflammatory properties. Furthermore, BALB/c mice induced with experimental pancreatitis using cholecystokinin- (CCK-) 8 showed decreased serum lipase levels due to FKA pretreatment. We conclude that with its potent antioxidant and anti-inflammatory properties, chalcone flavokawain A could be a novel therapeutic agent in the treatment of inflammation-associated diseases.

Vascular oxidative stress, inflammatory response, and proliferation are crucial mediators of vascular dysfunction which contribute to the pathology of hypertension. A tripeptide, LRW (Leu-Arg-Trp), was characterized from pea protein legumin, and its previously studied isomer IRW (Ile-Arg-Trp) was reported to exhibit antihypertensive activity via activation of angiotensin-converting enzyme 2. The objective of the current study was to explore the effects of LRW on vascular stress in vascular smooth muscle cells (VSMCs) under angiotensin II (Ang II)-induced cellular stress. LRW treatment could decrease Ang II-triggered superoxide production, inflammation, and proliferation in VSMCs. The abovementioned advantageous effects appeared to involve the upregulation of the ACE2-Ang-(1-7)-MasR axis and modulation of the nuclear factor-κB pathway. These findings specified the prospective role of LRW as a functional food ingredient or nutraceutical in the prevention of cardiovascular diseases, particularly hypertension and vascular damage.

Food protein-derived bioactive peptides have been recognized as a promising candidate for the development of functional foods or nutraceuticals. Peptides exhibiting antioxidant, anti-proliferative and anti-hypertensive activities have been characterized from corn proteins while the knowledge on the presence of immunomodulatory peptides in corn proteins is limited. The objective of this study was to identify the immunomodulatory peptides from corn proteins using interleukin 6 (IL-6) in human macrophage-like U937 cells as the marker. Results indicated that zein protein hydrolysate digested by thermolysin showed a high yield of peptides with potent activity, which was then used for further fractionation by RP-HPLC. We identified five peptides using LC–MS/MS, among which, peptide FLPFNQL showed the highest activity reducing IL-6 production by 57.7% ± 6.1%.

Background Vitamin D receptor (VDR) plays a vital protective role in oral and colonic epithelial cells. Albeit we know that VDR expression is reduced in the mucosal epithelial layers of autoimmune diseases, the mechanism by which VDR is decreased remains elusive. Methods VDR and zinc finger protein 36 (ZFP36) levels in human samples and cell lines were detected by real-time PCR, western blot and immunostaining. Luciferase report assay was used to test cis-elements in VDR gene promoter, real-time PCR was applied to measure mRNA decay and western blot was performed to evaluate protein degradation. RNA affinity chromatography assay was used to test protein-mRNA interaction. Co-immunoprecipitation was used to detect protein–protein interaction. The role of ZFP36 in AU-rich elements (AREs) in the 3′ untranslated region (UTR) of VDR mRNA was also measured by luciferase report assay. Results We identify ZFP36 can bind with the AREs in the 3’UTR of VDR mRNA, leading to mRNA degradation in oral and colonic epithelial cells under inflammatory circumstance. Either ZFP36 protein or AREs of VDR mRNA mutation abolishes this protein-mRNA binding process. After the key amino acid’s mutation, ZFP36 fails to decrease VDR mRNA expression. We also find that VDR physically binds with Y box-binding protein 1 (YBX-1) to block YBX-1’s nuclear translocation and ameliorate cell death in the presence of inflammation. Conclusion These findings provide insights into the cause of VDR decrease in oral and colonic epithelial cells under inflammatory condition and explain how VDR maintains cell viability in these cells.

Cisplatin-induced nephrotoxicity is associated with gut microbiota disturbance. The present study aimed to investigate whether supplementation of Lactobacillus reuteri and Clostridium butyricum (LCs) had a protective effect on cisplatin-induced nephrotoxicity through reconstruction of gut microbiota. Wistar rats were given different treatments: control, cisplatin (Cis), cisplatin + C. butyricum and L. reuteri (Cis+LCs), and C. butyricum and L. reuteri (LCs). We observed that cisplatin-treated rats supplemented with LCs exhibited significantly decreased renal inflammation (KIM-1, F4/80, and MPO), oxidative stress, fibrosis (collagen IV, fibronectin, and a-SMA), apoptosis, concentration of blood endotoxin and indoxyl sulfate, and increased fecal butyric acid production compared with those without supplementation. In addition, LCs improved the cisplatin-induced microbiome dysbiosis by maintaining a healthy gut microbiota structure and diversity, depleting Escherichia-Shigella and the Enterobacteriaceae family, and enriching probiotic Bifidobacterium, Ruminococcaceae, Ruminiclostridium_9, and Oscillibacter. Moreover, the LCs intervention alleviated the cisplatin-induced intestinal epithelial barrier impairment. This study indicated LCs probiotic serves as a mediator of the gut–kidney axis in cisplatin-induced nephrotoxicity to restore the intestinal microbiota composition, thereby suppressing uremic toxin production and enhancing butyrate production. Furthermore, the renoprotective effect of LCs is partially mediated by increasing the anti-inflammatory effects and maintaining the integrity of the intestinal barrier.

Metformin is the first-line pharmacotherapy for type 2 diabetes mellitus (T2D). Metformin exerts its glucose-lowering effect primarily through decreasing hepatic glucose production (HGP). However, the precise molecular mechanisms of metformin remain unclear due to supra-pharmacological concentration of metformin used in the study. Here, we investigated the role of Foxo1 in metformin action in control of glucose homeostasis and its mechanism via the transcription factor Foxo1 in mice, as well as the clinical relevance with co-treatment of aspirin. We showed that metformin inhibits HGP and blood glucose in a Foxo1-dependent manner. Furthermore, we identified that metformin suppresses glucagon-induced HGP through inhibiting the PKA→Foxo1 signaling pathway. In both cells and mice, Foxo1-S273D or A mutation abolished the suppressive effect of metformin on glucagon or fasting-induced HGP. We further showed that metformin attenuates PKA activity, decreases Foxo1-S273 phosphorylation, and improves glucose homeostasis in diet-induced obese mice. We also provided evidence that salicylate suppresses HGP and blood glucose through the PKA→Foxo1 signaling pathway, but it has no further additive improvement with metformin in control of glucose homeostasis. Our study demonstrates that metformin inhibits HGP through PKA-regulated transcription factor Foxo1 and its S273 phosphorylation.

KIT is a tyrosine kinase receptor involved in carcinogenesis. Two alternatively spliced transcripts, differed from presence of four amino acids (GNSK) at exon 9 of c-kit, were identified in various human tumours and canine hemangiosarcoma (HSA). The biological function and clinical implications of these isoforms have not yet been elucidated in canine tumours. The current study aimed to validate the expression profile and ultimately to evaluate the correlation of c-kit isoform levels with clinicopathological factors of canine mammary tumours (CMTs). In total, the expression profiles of c-kit isoforms in 196 samples obtained from normal mammary glands (NMGs) of healthy controls and dogs with CMTs, benign and malignant CMTs, and HSAs were determined by polymerase chain reaction (PCR) and quantified via real-time PCR. Overall, the expression levels of the two isoforms were equivalent in NMGs, whereas the GNSK- /GNSK+ ratio sharply increased to 7.44- and 8.33-fold, indicating abundant GNSK- isoforms in benign and malignant CMTs, respectively. However, a significant decrease in GNSK- expression was detected in dogs with high-grade malignant CMTs (mCMTs) and with metastatic CMTs compared with expression in those with a lower grade and non-metastatic CMTs. In addition, the median survival time was shorter in mCMT canines with a lower GNSK- /GNSK+ ratio than that in mCMT canines with a higher ratio (899 days vs 1534 days). In conclusion, two c-kit isoforms are ubiquitously expressed with great variability in HSAs and CMTs with both benign and malignant status. The GNSK- /GNSK+ ratio could serve as a prognostic indicator for dogs with mCMTs.

The impact of the irradiation side on the cross sections of single-event upsets (SEUs) induced by neutrons was investigated by performing neutron irradiation measurements and simulations. A test board equipped with 65-nm bulk 6-T CMOS static random access memories was irradiated by quasi-monoenergetic neutrons, and the number of SEUs was counted. The number of SEUs obtained by the board-side irradiation was approximately 20% to 30% smaller than that obtained by irradiation on the plastic package side. We also investigated the impact of irradiation side on the soft error rates (SERs) obtained with by the terrestrial neutron energy spectrum via a Monte Carlo simulation. The SER obtained from the plastic package side irradiation was approximately twice that obtained for the board side irradiation, indicating that SERs can be reduced by equipping the device with the package side facing downward. Additionally, based on the simulation, the atomic composition of the material placed in front of the memory chip has a considerable influence on the SER because production yields and angular distributions of secondary H and He ions (the main causes of SEUs) depend on the composition. In particular, the existence of hydrides, such as plastic, considerably increases the SER because of the higher production yields of secondary H ions that are generated via elastic scattering of neutrons with hydrogen atoms.

Emerging environmentally friendly materials with ultrahigh-temperature thermal insulation, high fire resistance, and cost efficiency are in high demand in the fields of aerospace and high-rise buil...

Background Breast cancer is the most prevalent cancer among women. In triple-negative breast cancer (TNBC) cells, a novel quinone derivative, coenzyme Q0 (CoQ0), promotes apoptosis and cell-cycle arrest. This study explored the anti-epithelial–mesenchymal transition (EMT) and antimetastatic attributes of CoQ0 in TNBC (MDA-MB-231). Methods Invasion, as well as MTT assays were conducted. Lipofectamine RNAiMAX was used to transfect cells with β-catenin siRNA. Through Western blotting and RT-PCR, the major signaling pathways’ protein expressions were examined, and the biopsied tumor tissues underwent immunohistochemical and hematoxylin and eosin staining as well as Western blotting. Results CoQ0 (0.5–2 μM) hindered tumor migration, invasion, and progression. Additionally, it caused MMP-2/− 9, uPA, uPAR, and VEGF downregulation. Furthermore, in highly metastatic MDA-MB-231 cells, TIMP-1/2 expression was subsequently upregulated and MMP-9 expression was downregulated. In addition, CoQ0 inhibited metastasis and EMT in TGF-β/TNF-α-stimulated non-tumorigenic MCF-10A cells. Bioluminescence imaging of MDA-MB-231 luciferase–injected live mice demonstrated that CoQ0 significantly inhibited metastasis of the breast cancer to the lungs and inhibited the development of tumors in MDA-MB-231 xenografted nude mice. Silencing of β-catenin with siRNA stimulated CoQ0-inhibited EMT. Western blotting as well as histological analysis established that CoQ0 reduced xenografted tumor development because apoptosis induction, cell-cycle inhibition, E-cadherin upregulation, β-catenin downregulation, and metastasis and EMT regulatory protein modulation were observed. Conclusions CoQ0 inhibited the progression of metastasis as well as EMT (in vitro and in vivo). The described approach has potential in treating human breast cancer metastasis. Electronic supplementary material The online version of this article (10.1186/s13046-019-1196-x) contains supplementary material, which is available to authorized users.

Background Sphingosine kinase 1 (SPHK1) is an enzyme that converts pro-apoptotic ceramide and sphingosine into anti-apoptotic sphingosine-1-phosphate. There is growing evidence that SPHK1 activation promotes oncogenic transformation, tumor growth, chemotherapy resistance, and metastatic spread. High SPHK1 expression has been associated with a poor prognosis in several human cancers. Results In the present study, the expression level of SPHK1 was examined in feline mammary tumor (FMT) specimens, and the IHC expression level of SPHK1 was associated with the histological grade of FMTs. IHC analysis of 88 FMT cases revealed that the expression level of SPHK1 was upregulated in 53 tumor tissues (60.2%) compared to adjacent mammary tissues. SPHK1 expression in FMTs was significantly associated with histological grade, presence of lymphovascular invasion, and estrogen receptor negativity. Treatment of primary FMT cells with SPHK1 inhibitors reduced cell viability, indicating that SPHK1 acts to promote FMT cell survival. These results indicate that SPHK1 may play an important role in FMTs and may be a therapeutic target in cats with FMT. Conclusions SPHK1 over-expression in breast cancer tissues is associated with a poor prognosis in humans. SPHK1 over-expression in more aggressive FMTs provides support for a potential role of SPHK1 inhibitors for the treatment of FMTs. Targeting SPHK1 has potent cytotoxic effects in primary FMT cells. These findings suggest that further examination of the role SPHK1 plays in FMTs will pave the way for the investigation of SPHK1 inhibitors in future clinical applications. Electronic supplementary material The online version of this article (10.1186/s12917-019-1883-z) contains supplementary material, which is available to authorized users.

To overcome the contradiction among flame retardancy, smoke suppression and thermal insulation for polyurethane foams (PUFs), in this manuscript, a novel functionalized graphene (FGN) is designed and prepared from expandable graphite (EG) and phosphorus-containing compounds. This FGN decorated with phosphorus-containing epoxy shows excellent compatibility with polyurethane matrix, leading to an improved compressive strength and decreased thermal conductivity as low as 0.02975 W/(m∙K). Notably, the resultant PUFs with FGNs exhibit great fire resistance and smoke suppression performance. With only 50 pphp FGNs (6.1 wt%) incorporated, the composite foam can pass the UL-94V-0 rating with a high limiting oxygen index value of 27. More importantly, the incorparation of FGNs not only effectively reduces the heat release rate (HRR) and total release rate (THR) of PUFs, but also significantly suppresses smoke release of materials during combustion. The mean specific extinction area (mSEA) and total smoke production (TSP) values of the composite foam can be reduced to 208.52 m2/s (−70.0%) and 2.08 m2/m2 (−66.0%), respectively. These characteristics with high fire resistance, excellent smoke suppression and low thermal conductivity very beneficial for polyurethane foams used as thermal isolation materials.

Acrylamide (ACR), which is formed during the Maillard reaction, is used in various industrial processes. ACR accumulation in humans and laboratory animals results in genotoxicity, carcinogenicity, neurotoxicity, and reproductive toxicity. In this study, we investigated the mechanisms by which ACR may induce vasorelaxation and neuromuscular toxicity. Vasorelaxation was studied using an isolated rat aortic ring model. The aortic rings were divided into the following groups: with or without endothelium, with nitric oxide synthase (NOS) inhibition, with acetylcholine receptor inhibition, and with extracellular calcium inhibition. Changes in tension were used to indicate vasorelaxation. Neuromuscular toxicity was assessed using a phrenic nerve–diaphragm model. Changes in muscle contraction stimulated by the phrenic nerve were used to indicate neuromuscular toxicity. ACR induced the vasorelaxation of phenylephrine-precontracted aortic rings, which could be significantly attenuated by NOS inhibitors. The results of the phrenic nerve–diaphragm experiments revealed that ACR reduced muscle stimulation and contraction through nicotinic acetylcholine receptor (AChR). ACR-induced vasotoxicity was regulated by NOS through the aortic endothelium. Nicotinic AChR regulated ACR-induced neuromuscular blockage.

Gallic acid (GA) is a simple polyphenol found in food and traditional Chinese medicine. Here, we determined the effects of GA administration in a combined mouse model of high-fat diet (HFD)-induced obesity and low-dose streptozotocin (STZ)-induced hyperglycemia, which mimics the concurrent non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes pathological condition. By combining the results of physiological assessments, pathological examinations, metabolomic studies of blood, urine, liver, and muscle, and measurements of gene expression, we attempted to elucidate the efficacy of GA and the underlying mechanism of action of GA in hyperglycemic and dyslipidemic mice. HFD and STZ induced severe diabetes, NAFLD, and other metabolic disorders in mice. However, the results of liver histopathology and serum biochemical examinations indicated that daily GA treatment alleviated the high blood glucose levels in the mice and decelerated the progression of NAFLD. In addition, our results show that the hepatoprotective effect of GA in diabetic mice occurs in part through a partially preventing disordered metabolic pathway related to glucose, lipids, amino acids, purines, and pyrimidines. Specifically, the mechanism responsible for alleviation of lipid accumulation is related to the upregulation of β-oxidation and ketogenesis. These findings indicate that GA alleviates metabolic diseases through novel mechanisms.

The success of boron neutron capture therapy (BNCT) mainly depends on the boron concentration in the tumor and a high tumor/normal tissue (T/N) boron ratio or a high tumor/blood (T/B) boron ratio. Therefore, the effective enhancement of boron ratios is the first priority. Our study investigated whether a low-dose of γ-radiation (LDR) could improve boron ratios and enhance the therapeutic effects of BNCT in an orthotopic human oral squamous cell carcinoma-bearing animal model. SAS/luc cells were used to establish the orthotopic tumor-bearing model. The pharmacokinetics of boronophenylalanine (BPA) administration with 400 mg/kg of body weight both alone and in combination with LDR (0.1 Gy) was evaluated, and BNCT was performed at the Tsing Hua Open-pool Reactor (THOR). The radiation doses were evaluated using a treatment planning system. Moreover, tumor growth and metastasis were monitored via bioluminescence imaging (BLI). The therapeutic effects after BNCT were evaluated using BLI, histopathological findings and the overall survival rate. LDR increased the BPA accumulation in tumors by 52.2%. T/N and T/B ratios were enhanced from 3.77 to 5.31 and from 3.47 to 4.46, respectively. Radiation dose was increased by 44.3%. Notably, tumor recurrence and cervical lymph node metastasis were observed in the BNCT group, which had a survival rate of 50%. Complete responses were found in the combined-treatment group, which had a survival rate of 100%. No toxicity was found according to the histopathological findings. Conclusively, LDR increased BPA accumulation in the tumor and the T/N and T/B ratios, resulting in BNCT efficacy improvement and the overall survival rate extension.

Background: Although considered a rare form of skin cancer, malignant melanoma has steadily increased internationally and is a main cause of cancer-associated death worldwide. The treatment options for malignant melanoma are very limited. Accumulating data suggest that the natural compound, capsaicin, exhibits preferential anticancer properties to act as a nutraceutical agent. Here, we explored the underlying molecular events involved in the inhibitory effects of capsaicin on the growth of melanoma cells.Methods: The cellular thermal shift assay (CETSA) and isothermal dose response fingerprint (ITDRFCETSA) were utilized to validate the binding of capsaicin with the tumor-associated NADH oxidase, tNOX (ENOX2) in melanoma cells. We also assessed the cellular impact of capsaicin-targeting of tNOX on A375 cells by flow cytometry and protein analysis. The essential role of tNOX in tumor- and melanoma-growth limiting abilities of capsaicin was evaluated in C57BL/6 mice.Results: Our data show that capsaicin directly targets cellular tNOX to inhibit its enzymatic activity and enhance protein degradation capacity. The inhibition of tNOX by capsaicin is accompanied by the attenuation of SIRT1, a NAD+-dependent deacetylase that enhances ULK1 acetylation to induce ROS-dependent autophagy in melanoma cells. Capsaicin treatment of mice implanted with melanoma cancer cells suppressed tumor growth by down-regulating tNOX and SIRT1, which was also seen in an in vivo xenograft study with tNOX-depleted melanoma cells. Conclusions: Together, our findings suggest that tNOX expression is important for the growth of melanoma cancer cells both in vitro and in vivo, and that inhibition of the tNOX-SIRT1 axis contributes to inducting cytotoxic ROS-dependent autophagy in melanoma cells.

Polysaccharides are one of the main active substances in Ganoderma atrum (G. atrum). The purpose of this study was to explore the protective effect of a G. atrum polysaccharide (PSG-1) on DSS-induced colitis and the underlying mechanism. The results showed that PSG-1 could maintain the integrity of the intestinal structure by promoting the expression of goblet cells and levels of tight junction proteins in the colon of DSS-induced colitis mice. Furthermore, PSG-1 relieved the inhibition of Bcl-2 and the overexpression of caspase-3 and caspase-9 caused by DSS. Simultaneously, PSG-1 restored the expression of Atg5, Atg7 and beclin-1 and inhibited the p-akt and p-mTOR levels, suggesting that PSG-1 promoted autophagy via the Akt/mTOR pathway. Moreover, PSG-1 inhibited the content of DCs in the colon and modulated the expression of IL-10 in DCs. In conclusion, PSG-1 alleviated DSS-induced ulcerative colitis by protecting the apoptosis/autophagy-regulated physical barrier and the DC-related immune barrier.

Spent hens are a major byproduct of the egg industry but are rich in muscle proteins that can be enzymatically transformed into bioactive peptides. The present study aimed to develop a spent hen muscle protein hydrolysate (SPH) with antihypertensive activity. Spent hen muscle proteins were hydrolyzed by nine enzymes, either individually or in combination, 18 SPHs were assessed initially for their in vitro angiotensin-converting enzyme (ACE) inhibitory activity, and three SPHs, prepared by Protex 26L (SPH-26L), pepsin (SPH-P), and thermoase (SPH-T), showed promising activity and peptide yield. These three hydrolysates were further assessed for their angiotensin-converting enzyme 2 (ACE2) upregulating, antioxidant, and anti-inflammatory activities, only SPH-T upregulated ACE2 expression, while all three SPHs showed antioxidant and anti-inflammatory activities. During simulated gastrointestinal digestion, ACE2 upregulating, ACE inhibitory and antioxidant activities of SPH-T were not affected, but those of SPH-26L and SPH-P were reduced. ACE inhibitory activity of gastrointestinal-digested SPH-T was not affected after the permeability study in Caco-2 cells, while ACE2 upregulating, antioxidant and anti-inflammatory activities were improved, nine novel peptides with five&ndash, eight amino acid residues were identified from the Caco-2 permeate. Among these three hydrolysates, only SPH-T reduced blood pressure significantly when given orally at a daily dose of 1000 mg/kg body weight to spontaneously hypertensive rats. SPH-T can be developed into a promising functional food ingredient against hypertension, contributing to a more sustainable utilization for spent hens while generating extra revenue for the egg industry.

Chalcone flavokawain B (FKB) possesses a chemopreventive and anti-cancer activity. Doxorubicin is a chemotherapeutic DNA intercalating agent widely used in malignancy treatment. The present study investigated whether synergistic effects exist between the combination of FKB (1.25&ndash, 5 &micro, g/mL) and doxorubicin (0.5 &micro, g/mL) on the apoptosis and autophagy in human gastric cancer (AGS) cells, and the possible in vitro and in vivo mechanisms. The MTT assay measured cell viability. Various apoptotic-, autophagy-associated protein expression was determined by the Western blot technique. FKB+doxorubicin synergy was estimated by the Chou-Talalay combination index (CI) method. In vivo studies were performed on BALB/c mice. Results showed that compared to FKB/doxorubicin treatments, low doses of FKB+doxorubicin suppressed AGS cell growth. FKB potentiated doxorubicin-induced DNA fragmentation, apoptotic cell death, and enhanced doxorubicin-mediated mitochondrial, death receptor pathways. FKB+doxorubicin activated increased LC3-II accumulation, p62/SQSTM1 expression, and AVO formation as compared to the FKB/doxorubicin alone treatments indicating autophagy in these cells. The death mechanism in FKB+doxorubicin-treated AGS cells is due to the activation of autophagy. FKB+doxorubicin-mediated dysregulated Bax/Bcl-2, Beclin-1/Bcl-2 ratios suggested apoptosis, autophagy induction in AGS cells. FKB+doxorubicin-induced LC3-II/AVOs downregulation was suppressed due to an apoptotic inhibitor Z-VAD-FMK. Whereas, 3-methyladenine/chloroquine weakened FKB+doxorubicin-induced apoptosis (decreased DNA fragmentation/caspase-3). Activation of ERK/JNK may be involved in FKB+doxorubicin-induced apoptosis and autophagy. FKB+doxorubicin-triggered ROS generation, but NAC attenuated FKB+doxorubicin-induced autophagic (LC3 accumulation) and apoptotic (caspase-3 activation and PARP cleavage) cell death. FKB+doxorubicin blocked gastric cancer cell xenografts in nude mice in vivo as compared to FKB/doxorubicin alone treatments. FKB and doxorubicin wielded synergistic anti-tumor effects in gastric cancer cells and is a promising therapeutic approach.

In order to elucidate the possible genetic determinants of resistance to florfenicol and chloramphenicol in porcine Escherichia coli in Taiwan, 600 fecal samples of healthy pigs from 50 different farms were collected from 2003 to 2007. The florfenicol resistance in the isolated E. coli strains doubled from 39.2% in 2003 to 78.3% in 2007. A total of 351 florfenicol-resistant E. coli isolates were isolated from nursery pigs (61.5%), grower-finisher pigs (62.5%), and sows (51.5%). The prevalence of resistance genes, floR, cmlA, cat-1, cat-2 and cat-3, was 82.9, 61.3, 10.8, 3.7, and 0%, respectively. Of the 351 florfenicol-resistant isolates, 184 (52.4%) were positive for both floR and cmlA. Furthermore, the results of efflux inhibitor studies with Phe-Arg-β-naphthylamide showed a 4- to 64-fold decrease in the florfenicol MIC levels. The FloR efflux pump may play a role in phenicol resistance among porcine E. coli isolates in Taiwan. More detailed studies are required to focus on the public health concerns about the spread of antimicrobial resistance from animal food products to humans through the food chain.

Monascus purpureus is a fungus used in rice fermentation. Monascus-fermented rice is called red-mold rice (RMR) in Taiwan since the fermentation products contain a considerable amount of red pigments. The protective effects of RMR on oxidative stress in the testis and sperm were evaluated in this study. Zn deficiency was induced in rats by feeding them with a Zn-deficient diet for 12 weeks while the control rats were fed with a normal diet. The Zn-deficient rats were then divided into 6 groups, designated as Zn-deficient (ZD). Zn-compensated (ZC), IR (151 mg RMR/kg), 5R (755 mg RMR/kg), 1R+ZC (1RZ), and 5R+ZC (5RZ). The animals were administered with the mentioned diet (RMR/Zn) for 8 weeks. In the ZD rats, no spermatid cell formation was observed in the seminiferous tubular epithelia, and testis necrosis/atrophy was apparent. However, 5R and 5RZ administration improved testicular antioxidant enzyme activity, elevated serum testosterone levels, and increased sperm number in ZD rats; this treatment also exhibited inhibitory effects on caspase activities and reactive oxygen species (ROS) levels in the ZD rats, suggesting that RMR attenuated ZD-induced oxidative stress and testis apoptosis. The preventive activity against ZD-induced reproductive damage was more apparent in the 1RZ and 5RZ groups than in the ZC group, suggesting that RMR can serve as a supplement in adjuvant therapy for diseases associated with Zn deficiency.

Carbendazim (methyl 2-benzimidazolecarbamate) and its parent compound benomyl are systemic fungicides that have reproductive and developmental toxicity in male rats. The major objectives of this study were to determine the ability of carbendazim exposure in utero to alter androgen-dependent development markers in rat offspring and investigate the effects of antiandrogen flutamide on the carbendazim-mediated reproductive and developmental alterations. Pregnant female rats were treated with 6.25, 12.5 or 25 mg/kg carbendazim, 25, 50 or 100 mg/kg benomyl, and 0.6, 2.5 or 10 mg/kg flutamide by gavage once daily from gestational day 0 to 20. Alternatively, another group of female rats was cotreated with 25 mg/kg carbendazim or 100 mg/kg benomyl and 0.6, 2.5, and 10 mg/kg flutamide. The various treatments decreased the survival rates of pups on postnatal day (PND) 1 and 21. In male offspring, 12.5 and 25 mg/kg carbendazim increased anogenital distance (AGD), an androgen-dependent marker, on PND 2. Treatment with benomyl also increased AGD. Cotreatment with 25 mg/kg carbendazim with 0.6, 2.5, and 10 mg/kg flutamide blocked the androgenic effect on AGD induced by carbendazim. The androgenic effects of carbendazim and benomyl on AGD were reversible on PND 22 and later. Carbendazim had no effects on other androgen-dependent markers including testis and epididymis malformations, hypospadias, nipple retention, and organ weights of seminal vesicle and levator ani bulbocavernosus muscle on PND 56. Surprisingly, carbendazim antagonized the antiandrogenic effects on these markers induced by flutamide cotreatment. In female offspring, carbendazim produced synergistic effects on the flutamide cotreatment-mediated increases of organs weights in liver and kidney on PND 56. Carbenazim had no marked effects on female reproductive organs. These findings show that carbendazim exposure in utero displays a transient and weak androgenic effect and reduces flutamide antiandrogenicity in male rats. The fungicide enhances flutamide-mediated liver and kidney weight increases in female rats. The antagonistic and synergistic carbendazim and flutamide interactions in utero warrant further investigations.

This study investigated the effect of seaweed supplementation (Ulva lactuca (UL) or Sargassum hemiphyllum var. chinense (SHC)) on the distribution and metabolites of As in broiler breasts. Broilers fed 5% UL or 5% SHC ingested 1.4- or 78- fold greater total As than birds fed the control diet. The majority of As species were arsenate in the SHC feed and dimethylarsinic acid in breasts from chicks fed the SHC-containing diet. Arsenate and arsenobetaine were the dominant metabolites in the UL-containing feed, and arsenobetaine was the major metabolite in breasts from chicks fed the UL-containing diet. Feeding SHC enhanced hepatic S-adenosyl-methionine and arsenic methyltransferase, whereas feeding UL elevated renal arsenic methyltransferase. Taken together, considerable variation in the profiles of As species and As metabolites existed in broilers fed seaweed. The use of SHC-containing feeds in poultry production should be approached cautiously because of the potential accumulation of inorganic As species in chicken breasts.

The heme oxygenase-1 (HO1) catalyzes the degradation of heme into biliverdin, ferrous iron and carbon monoxide (CO). Although HO1 has long been considered as an anti-inflammatory molecule, recent studies showed that HO1 disrupts the mitochondrial function in hepatocytes, as well as drives inflammation and insulin resistance in mice and humans. Such different findings from the historical view impelled us to further investigate the roles of HO1 in glucose metabolism. In the present study, we found that overexpression of HO1 promoted hepatic glucose production (HGP) in hepatocytes from the wild type (WT) mice, which was comparable to the treatment of glucagon. Since the regulatory roles of the transcription factor forkhead box O1 (Foxo1) in HGP have been well recognized, we then generated the liver-specific Foxo1 knockout (L-FKO) mice to study the contribution of Foxo1 in mediating the effects of HO1. We found that HO1 overexpression did not have a significant effect in promoting HGP in hepatocytes from the L-FKO mice, suggesting HO1 improved HGP dependent on Foxo1. Besides, HO1 overexpression improved the mRNA levels of Foxo1-targeted gluconeogenic genes and increased the phosphorylation of Foxo1 at Ser273, which is a phosphorylation site integrating into the glucagon signaling. We also found that HO1 overexpression activated p38α and p65/NF-κB in hepatocytes. Further study using siRNA or specific inhibitor demonstrated that p65/NF-κB, but not p38α, mediated the HO1-induced pFoxo1-S273 and HGP in hepatocytes. We then explored the role of HO1-induced ferrous iron in activating p65/NF-κB and promoting HGP. We found that HO1 overexpression in hepatocytes substantially increased the intracellular ferrous iron. The pretreatment of iron chelator deferoxamine mesylate diminished the effects of HO1 overexpression on p65/NF-κB, pFoxo1-S273, and HGP. Taken together, results from this study revealed the mechanisms of HO1 in driving HGP, which is through the generation of ferrous iron. Disclosure W. Liao: None. W. Yang: None. Q. Pan: None. Z. Shen: None. W. Ai: None. S. Guo: None. Funding National Institutes of Health (R01DK120968)

The vasoconstricting effect of angiotensin II (Ang II) is mediated by Ang II type I receptor (AT1R); blocking or blunting AT1R is a key strategy for the development of antihypertensive drugs. Our previous study showed that the blood pressure lowering the activity of egg white hydrolysate (EWH) in spontaneously hypertensive rats was due to the downregulation of aortic AT1R expression, which promoted us to further identify the AT1R downregulating peptides in the present study. The protein expression of AT1R in a rat aortic vascular smooth muscle cell line A7r5 cells was used for the activity test. The hydrolysate was fractionated stepwise by C18 Sep-Pack cartridge and reverse-phase chromatography, and the peptide sequences were characterized by LC-MS/MS. Peptides including ITKPNDVYS, VVGSAEAGVDAAS, AVHAAHAEINEAGRE, AGREVVGSAEAGVD, and VVGSAEAGVD, were identified. ITKPNDVYS showed the most potent peptide for lowering the level of AT1R in A7r5 cells. These results suggested that ITKPNDVYS is the responsible peptide for lowering the AT1R level in EWH. PRACTICAL APPLICATIONS: A new peptide ITKPNDVYS was identified as a downregulator of AT1R from egg white hydrolysate, which provides a new approach for the development of food protein-derived antihypertensive peptides as nutraceuticals or functional food ingredients.

The impacts of hydrided and non-hydrided materials near transistors on neutron-induced single event upsets (SEUs) were investigated by simulating monoenergetic neutron irradiations on 65-nm technology bulk static random access memories. The onset energy of the SEUs induced by H ions depends on the shielding capability, i.e., the material and thickness, of components placed in front of transistors when those components do not contain hydrogen atoms. The shielding capability also influences the initial slope observed in the energy-dependence of SEU cross sections. Taking into account the non-hydrided component attached to memory cells used in the simulation, all experimental data measured at each neutron facility were reproduced well using SEU cross sections obtained by simulation. We also find that the effect of components near transistors on neutron-induced soft error rates is not negligible even for irradiation by white neutrons.

Bacterial infection triggers a cytokine storm that needs to be resolved to maintain the host’s wellbeing. Here we report that ablation of m6A methyltransferase subunit METTL14 in myeloid cells exacerbates macrophage responses to acute bacterial infection leading to high mortality due to sustained production of pro-inflammatory cytokines. METTL14 depletion blunts Socs1 mRNA m6A methylation and reduces YTHDF1 binding to the m6A sites, which diminishes SOCS1 induction leading to overactivation of TLR4/NF- k B signaling. Forced expression of SOCS1 in macrophages depleted of METTL14 or YTHDF1 rescues the hyper-responsive phenotype of these macrophages in vitro and in vivo. We further show that LPS treatment induces Socs1 m6A methylation and sustains SOCS1 induction by promoting FTO mRNA degradation, and forced FTO expression in macrophages mimics the phenotype of METTL14-depleted macrophages. We conclude that m6A methylation-mediated SOCS1 induction is required to maintain the negative feedback control of macrophage activation in response to bacterial infection.

MicroRNA-27a/b are small non-coding RNAs which are reported to regulate inflammatory response and cell proliferation. Although some studies have demonstrated that miR-27b is down-regulated in the oral specimens of patients suffering with oral lichen planus (OLP), the molecular mechanism of miR-27b decrease remains a large mystery, and the expression of miR-27a in OLP is not well explored. Here, we demonstrated both miR-27a and miR-27b, compared with healthy controls, were reduced in the oral biopsies, serum and saliva samples derived from OLP patients. The reductions of miR-27a/b were also confirmed in the lipopolysaccharide (LPS)- or activated CD4+ T cell-treated human oral keratinocytes (HOKs). Furthermore, we found vitamin D receptor (VDR) binding sites in the promoters of miR-27a/b genes and verified this finding. We also tested miR-27a/b levels in the oral epithelium from paricalcitol-treated, vitamin D deficient or VDR knockout mice. In the rescue experiments, we confirmed vitamin D and VDR inhibited LPS- or activated CD4+ T cell-induced miR-27a/b reductions in HOKs. In sum, our results show that vitamin D/VDR signaling induces miR-27a/b in oral lichen planus.

In an effort to overcome issues encountered in additive flame retardants for rigid polyurethane foams (RPUFs), a novel reactive flame-retardant triol (TDHTPP) based on a triazine and phosphate structure was designed and synthesized. This triol was chemically incorporated in the main chains of RPUFs as a chain-extender to prepare inherently flame-retardant RPUFs. TDHTPP showed good solubility in the polyols (polyol 4110 and PEG 400) of RPUF, making it convenient for industrial fabrication, such as in spay foaming. Excellent compatibility of TDHTPP with the polymer matrix endowed flame-retardant RPUFs (FR-RPUFs) much higher compressive strength than that of the neat RPUF, and a low thermal conductivity of ∼0.03 W/(m·K). Notably, with only 5 wt% of TDHTPP incorporated, the resultant RPUF displayed a UL-94 V-0 rating and more importantly, exhibited a great persistent flame retardancy during thermal accelerated aging tests at 140 °C for 96 h. Further characterization revealed that TDHTPP possessed both vapor-phase and condensed-phase flame-retardant behaviors, in which, vapor-phase action was dominant. This work provides a facile route to synthesize RPUFs with persistent flame retardancy, excellent thermal insulation and mechanical properties.

Alzheimer’s disease is a neurodegenerative disorder mainly characterized by β-amyloid deposit and tau hyperphosphorylation with no curative treatments. Curcumin (Cur) has been proved to have potential use in Alzheimer’s disease with its anti-amyloid, anti-inflammatory, and anti-oxidant properties, etc. However, its hydrophobicity and low bioavailability hinder its application. In this paper, we designed a novel brain-target nanoparticle, poly(lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-PEG) conjugated with B6 peptide and was loaded with Cur (PLGA-PEG-B6/Cur) and administered it into HT22 cells and APP/PS1 Al transgenic mice. The in vitro assays including dynamic light scattering (DLS), flow cytometry (FCM), red blood cell (RBC) lysis, and thromboelastography (TEG) analysis indicated that this nanoparticle could narrow the diameter of Cur, increase its cellular uptake and possess good blood compatibility. The results from Morris water maze proved that PLGA-PEG-B6/Cur could tremendously improve the spatial learning and memory capability of APP/PS1 mice, compared with native Cur. The ex vivo assays including Bielschowsky silver staining, immunostaining, and western blotting demonstrated that PLGA-PEG-B6/Cur could reduce hippocampal β-amyloid formation and deposit and tau hyperphosphorylation. Thus, we suggested that PLGA-PEG-B6/Cur nanoparticles would be of potential and promising use for the treatment of Alzheimer’s disease.

Herein, expandable graphite (EG) and aluminum hypophosphite (AP) are used to prepare flame-retardant polystyrene (PS) composites. The flame-retardant properties of the PS composites are investigated by the limiting oxygen index (LOI) test, vertical burning test (UL-94) and cone calorimetry test (CC). With 15 wt% EG or AP incorporated alone, the PS composites show limited improvement in LOI, and fail to pass the UL-94 test. In contrast, with 10 wt% EG and 5 wt% AP added, the sample (PS/10EG/5EG) passes the UL-94 V-0 rating, and its LOI value increases from 17% to 25.5%. CC results show that the PS/10EG/5AP has a significantly depressed peak heat release rate (PHRR) by 77.7%, total heat release (THR) by 39.3%, smoke product rate (SPR) by 78.2% and total smoke product (TSP) by 82.3%. Meanwhile, the flame-retardant mechanism of the PS composites is studied by SEM, XPS, TG-IR and Py-GC/MS, and the results of which indicating a combination of condensed-phase and gaseous-phase activity during combustion.

To overcome the poor compatibility, easy migration of additive flame retardants, a novel polyester polyol (DMOP) was synthesized from dimethyl methylphosphonate and diethanol amine through transesterification and used in the foaming formula to prepare inherent flame-retardant flexible polyurethane foams (FPUFs). DMOP mainly play soft segments in the foams which increases the flexibility and elongation at break. With a low incorporation amount of 10 php (ca. 6.3 wt%), the resultant FPUF can pass vertical burning test. More importantly, accelerated ageing tests at 140 °C for 64 h indicate the persistent flame retardancy of DMOP for FPUF. The thermogravimetric analysis (TGA) results reveal their lower thermal stability than that of ordinary polyurethane. The corresponding flame-retardant mechanism of DMOP-containing FPUFs is investigated by Pyrolysis gas chromatography and mass spectrometry (Py-GC/MS) and FTIR, which indicates the phosphorus in DMOP mainly played their role in the vapor phase. This work thus offers a facile route for preparing FPUFs with persistent, efficient flame retardancy.

A novel liquid phosphorus-containing polyol named as PDEO was prepared via reactions between ethylene glycol and phenylphosphonic dichloride. PDEO reacts with the -NCO-terminated prepolymers and forms urethane linkages in the chain extending reaction step, thus, it was used to prepare inherently flame-retardant flexible polyurethane foams (FPUFs). The structure and properties of flame-retardant FPUFs were characterized by scanning electron microscopy (SEM), tensile measurements, limiting oxygen index (LOI), vertical burning tests, cone calorimeter tests and thermogravimetric analysis (TGA). The vertical burning test demonstrated that fire extinguished instantly after the withdrawn of the pilot flame, while the PDEO loading was only 10 php. In addition, the persistent flame retardancy of PDEO in FPUFs was proved by thermal ageing test. The corresponding flame-retardant mechanism of PDEO-containing FPUFs was investigated by pyrolysis gas chromatography mass spectrometry (Py-GC/MS), X-ray photoelectron spectroscopy (XPS), SEM and FTIR, and the results indicated a gaseous phase dominated flame-retardant mechanism of PDEO.

The cytotoxicity of phenolic antioxidants had attracted marked attention, posing serious challenges to food safety. This paper presented a screening method for two major phenolic antioxidants (butylated hydroxytoluene and tert-butylhydroquinone) added in edible oils. To specifically visualize the targeted compounds after developing with toluene/ethyl acetate/methanol 8:1:1 (v/v/v) to 70 mm solvent front, the plate was subjected to a standardized 1,1-diphenyl-2-picrylhydrazyl assay. In addition to synoptical eye inspection, accurate quantification was realized by modified densitometric measurements: fluorescence mode, excitation wavelength 530 nm (D2 and W lamp) without optical filter, which offered satisfactory sensitivity (8.5–17.5 mg/kg) and acceptable linearity (R2 > 0.999 within 50–200 ng/zone). Moreover, the established method was validated with edible oil samples, against EU Directive 2006/52/EC. Apart from that, the unambiguous confirmation of positive results was conveniently achieved by TLC-MS interface-mediated mass spectrometry. Featuring the merits of screening conception, the proposed method not only reached the goal of accurate quantification and conclusive identification of multi-phenolic antioxidants, but also excellently balanced the simplicity, detectability, and throughput of the screening workup. Therefore, it might be an attractive alternative to conventional methods.

Baicalin is the main flavonoid from the roots of an important medicinal plant, Scutellaria baicalensis, which shows a variety biological activities. Psoriasis is a chronic immune-mediated inflammatory disease that affects the skin. The unmet need of psoriasis is that many patients do not respond adequately to available clinical treatment. In this study, we found that baicalin showed inhibited dermal inflammation in a murine model of psoriasis via topical application of imiquimod. After a 5-day topical imiquimod application, baicalin or the control vehicle cream was to applied to the lesions of BALB/c mice for a further 4 days. The erythema, scaling, and thickness of the epidermal layer significantly improved in the baicalin-treated mice. The levels of interleukin-17A, interleukin-22, interleukin-23, and tumor necrosis factor in the skin significantly decreased after baicalin treatment. Baicalin also inhibited imiquimod-induced interleukin-17A production in skin draining lymph node cells. The infiltration of γδ T cells into the skin lesions induced by imiquimod was also suppressed after baicalin treatment. These results suggest that baicalin inhibited skin inflammation through the inhibition of the interleukin-17/interleukin-23 axis in a murine model of psoriasis.

Angiotensin I converting enzyme (ACE) plays an important role in regulation of blood pressure as it converts angiotensin I into angiotensin II (a potent vasoconstrictor). Food protein-derived ACE inhibitory peptides have been considered as a safer alternative to antihypertensive drugs. In our previous study, three ACE inhibitory peptides were characterized from egg white ovotransferrin and their antihypertensive activity has been validated in spontaneously hypertensive rats. However, it is too costly to prepare these peptides from purified egg white ovotransferrin. The aims of the study were to determine the feasibility of preparing these peptides using egg white and then to optimize the conditions of preparing egg white hydrolysate. Taguchi's method was used to design experiments for optimization, which was established as follows: substrate %, pH of thermoase, time of thermoase digestion, ratio of pepsin to substrate, pH of pepsin, temperature of pepsin, and time of pepsin digestion were 7.5%, pH 8, 90 min, 1%, pH 2.5, 55 °C, and 180 min, respectively. The ACE inhibitory activity (IC50 value) and peptide yield obtained under optimal condition were 30 ± 2 μg/mL and 77.5% ± 0.3%, respectively, which were comparable to the predicted values. Hydrolysate prepared at 150 L reactor showed comparable activity but low peptide yield. Results of this study demonstrated the feasibility of using egg white protein as the starting material to prepare a functional ingredient with potent ACE inhibitory activity.

Excessive proliferation, inflammation, oxidative stress, and migration induced by angiotensin II (Ang II), occurring in vascular smooth muscle cells (VSMCs) during vascular remodelling, are major pathogenesis of hypertension. Antihypertensive peptides derived from food proteins are promising alternatives in preventing/treating hypertension and associated complications. In addition to reducing high blood pressure in spontaneously hypertensive rats, egg white ovotransferrin-derived antihypertensive IRW (Ile-Arg-Trp) was shown to exert antiproliferative, antioxidant, and anti-inflammatory effects in A7r5 cells (a vascular smooth muscle cell line) against Ang II stimulation, further indicating its potential in retarding vascular remodelling. Since its regulatory role in migration of VSMC is unclear, the objective of this study was to evaluate the antimigrant activity of IRW in Ang II-stimulated A7r5 cells. It was found that IRW could downregulate matrix metallopeptidase 9 (MMP9) expression and inhibit migration of Ang II-stimulated A7r5 cells, which was associated with inactivation of p38/MAPK signaling. More importantly, the antimigrant activity of IRW in Ang II-stimulated A7r5 cells was dependent on angiotensin type I receptor (AT1R). Our study provided the first evidence that egg ovotransferrin-derived antihypertensive peptide IRW inhibited migration of VSMCs.

This study aimed to investigate whether HMGB1 (high mobility group box-1 protein) and receptor for advanced glycation end products (RAGE) were involved in the irradiation-induced endothelial barrier damage and their mechanism. We constructed the damage model of endothelium barrier model with bEnd.3 cells. The permeability of endothelial barrier was detected by sodium fluorescein (Na-F) permeation test, and the irradiation dose which could induce permeability transition was determined by being exposed to different irradiation doses (5, 10, 15, 20 Gy). MTT assay was applied to detect cell viability under different concentrations of HMGB1, glycyrrhizic acid (GA, a specific inhibitor of HMGB1), and FPS-ZM1 (a blood-brain-barrier permeant blocker of RAGE V domain-mediated ligand binding). The expression of HMGB1, RAGE, and related molecules involved in MAPK signaling pathway, MMP-2, MMP-9, ZO-1, and claudin 5 of differently treated groups were measured by qRT-PCR, western blot, and immunofluorescence. Cells possessed stable endothelial barrier function on 4-7 days after seeded on transwell plates. The permeability of endothelial barrier would change under at least 10 Gy radiation. Both radiation and HMGB1 treatment alone could improve the permeability. After irradiation, the expressions of HMGB1 and RAGE increased and MAPK signal pathway was activated. Meanwhile, MMP-2 and MMP-9 were overexpressed, while the expression of tight junction proteins ZO-1 and claudin 5 was decreased. Radiation could activate MAPK signaling pathway through promoting the expression of HMGB1 and RAGE, which further led to endothelial barrier injury and changed its permeability.

The serious cytotoxicity of tyramine attracted marked attention as it induced necrosis of human intestinal cells. This paper presented a novel and facile high performance thin-layer chromatography (HPTLC) method tailored for screening tyramine in cheese. Separation was performed on glass backed silica gel plates, using methanol/ethyl acetate/ammonia (6/4/1 v/v/v) as the mobile phase. Special efforts were focused on optimizing conditions (substrate preparation, laser wavelength, salt types and concentrations) of surface enhanced Raman spectroscopy (SERS) measurements directly on plates after derivatization, which enabled molecule-specific identification of targeted bands. In parallel, fluorescent densitometry (FLD) scanning at 380

Neurotropin (NTP) is a widely used drug in China and Japan mainly for the treatment of chronic pain and peripheral inflammation. Nevertheless, the effects of NTP on neuroinflammation have not been explored. In this study, we investigated the anti-inflammatory effects of NTP in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells and its underlying mechanisms. BV-2 cells were pretreated with NTP for 12 h before exposure to LPS. The expression of pro-inflammatory cytokines (TNF-α and IL-6) were detected by RT-PCR and EILSA at mRNA and protein levels, respectively. Western blotting was conducted to measure the protein levels of major genes in MAPKs and NF-κB signaling pathways. Results demonstrated that NTP could attenuate the production of pro-inflammatory cytokines. Furthermore, NTP inhibited the activation of NF-κB signaling by decreasing the translocation of NF-κB p65 to the nucleus and suppressed the MAPKs signaling pathway via inhibition of the phosphorylation of p38, ERK and JNK. Taken together, these findings suggest that neurotropin exerts anti-inflammatory effects by suppressing the production of pro-inflammatory mediators via inhibition of NF-κB and MAPKs signaling pathways in LPS-stimulated BV-2 cells. Keywords: Neurotropin, Neuroinflammation, NF-κB, MAPKs, LPS

Poly(vinyl alcohol)/montmorillonite aerogels with high thermal stability and flame retardancy were prepared with a facile heat treatment method, in which the poly(vinyl alcohol)/montmorillonite aerogels was first prepared by an eco-friendly freeze-drying method, following by a heat treatment process. The structure of the aerogels before and after heat treatment process was characterized by Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). The thermal stability of the aerogel treated for 3 h at 200 °C was improved significantly, which was accompanied by a slight decrease of mechanical property. Meanwhile, cone calorimetry (CC) test revealed that the flame-retardant performance of the heat treated aerogel was improved remarkably.

Recent research of hydrogel actuators is still not sophisticated enough to meet the requirement of fast, reversible, complex, and robust reconfiguration. Here, we present a new kind of poly( N-isopropylacrylamide)/graphene oxide gradient hydrogel by utilizing direct current electric field to induce gradient and oriented distribution of graphene oxide into poly( N-isopropylacrylamide) hydrogel. Upon near-infrared light irradiation, the hydrogel exhibited excellent comprehensive actuation performance as a result of directional bending deformation, promising great potential in the application of soft actuators and optomechanical system.

Quercetin, a flavonol, displays anti-inflammatory and anti-cancer properties. This study aimed to investigate whether a diet containing 0.1% or 1% quercetin (LQ and HQ, respectively) enhances the anti-tumor effects of trichostatin A (TSA) and prevents muscle wasting induced by TSA. The positive control group received quercetin intraperitoneally (IQ). Three weeks after injecting A549 cells, nude mice were given TSA alone or in combination with quercetin administered orally or intraperitoneally for 16 weeks. Tumor volumes as well as body, muscle and epididymal fat weights were determined during or after the experiment. Quercetin given as a diet supplement dose-dependently enhanced the anti-tumor potency of TSA (p < 0.05). The enhancing effect of HQ was similar to that of IQ. HQ also significantly increased the expression of p53, a tumor suppressor, in tumor tissues compared with the TSA alone group. In addition, TSA-induced loss of gastrocnemius muscle weight was inhibited by oral quercetin in a dose dependent manner; the efficiencies of LQ and HQ were similar to or better than IQ. Moreover, both LQ and HQ decreased TSA-induced activation of Forkhead box O1 (FOXO1), a crucial transcription factor that regulates muscle wasting associated genes. Consistently, LQ and HQ suppressed muscle wasting associated proteins atrophy gene-1 and muscle ring-finger protein-1 expression as well as increased the myosin heavy chain level in the gastrocnemius muscles. Besides, quercetin attenuated TSA-increased oxidative damage and proinflammatory cytokines (p < 0.05). These findings demonstrate that a diet containing 0.1% or 1% quercetin enhances the antitumor effect of TSA and prevents TSA-induced muscle wasting.

Surface-modified nano-SiO2 is a common additive in many products. However, the safety of nano-SiO2 products under various modifications is still unclear. In this study, we investigated the genotoxicity and acute pulmonary toxicity of nano-SiO2 with or without modification. The samples used in this study included: sample A (SA, 55.16 nm, 411.3 mg/mL), modified sample A (mSA, 82.29 nm, 37.7 mg/mL), sample B (SB, 22 nm, 358.0 mg/mL), and modified sample B (mSB, 86.64 nm, 37.7 mg/mL). In the genotoxicity study, we conducted an Ames test, chromosomal aberration test (CA), and a micronucleus (MN) test. The SA, mSA, and mSB groups showed negative results in all these genotoxicity tests. Only SB showed a weakly positive reaction in these assays, but the genotoxicity could be reversed after S9 metabolism or modification. In the acute pulmonary toxicity test, the rats were given an intratracheal instillation (IT) (0.5 mL/kg) of diluted samples and sacrificed after 1 or 14 days. The mortality rate, number of leukocytes and cytokines of TNF-α in the bronchoalveolar lavage fluid (BALF), and the pathology in the lungs were determined. The results revealed that mSA posed acute toxicity in rats. After modification, the pulmonary toxicity was increased in mSA but decreased in mSB on Day 1, and no significant difference was observed on Day 14. In conclusion, there was no observed genotoxicity in either SA or SB, while mSA posed acute inhalation toxicity to rats that decreased in mSB after modification. This indicates that the decrease in pH level in SA and decrease in the solid content in SB are considered after the trifluorosilane surface-modified amorphous nano-silica.

In this study, canine transmissible venereal tumors (CTVTs) were evaluated for tumor-infiltrating lymphocytes, MHC class II antigen expression, melanoma antigen A (MAGE-A protein), and P-glycoprotein (P-gp). Vincristine (VCR)-sensitive CTVTs (VSCTVTs) were evaluated before and after VCR treatment. Immunohistochemical analysis was performed to evaluate the numbers of CD3[Formula: see text] lymphocytes, CD79a[Formula: see text] lymphocytes, and MHC II[Formula: see text] CTVT cells. Expression levels of P-gp, MAGE-A, and MHC class II antigen were evaluated. The numbers of CD3[Formula: see text] lymphocytes, CD79a[Formula: see text] lymphocytes, and MHC II[Formula: see text] CTVT cells were significantly elevated ([Formula: see text]). After VCR treatment, 100% (8/8) of VSCTVTs exhibited significantly higher MAGE-A expression in CTVT cells, compared with 74% (20/27) of VSCTVTs before VCR treatment. Strong expression of P-gp was found in 14.2% (1/7) of VSCTVTs after VCR treatment compared with VSCTVTs before treatment (83.3%, 5/6). These results demonstrated that regression of VSCTVTs following VCR treatment was associated with an obvious increase in the proportion of MHC class II[Formula: see text] CTVT cells and a significant increase in infiltration by T (CD3[Formula: see text] and B (CD79a[Formula: see text] lymphocytes, as well as decreased expression of P-gp and increased expression of MAGE-A in CTVT cells.