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Melanoma has a high propensity to metastasize and exhibits a poor response to classical therapies. Dysregulation of the chemokine receptor gene CXCR4 is associated with melanoma progression, and although n-3 polyunsaturated fatty acids (PUFAs) are known to be beneficial for melanoma prevention, the underlying mechanism of this effect is unclear. Here, we used the n-3 fatty acid desaturase (Fat-1) transgenic mouse model of endogenous n-3 PUFA synthesis to investigate the influence of elevated n-3 PUFA levels in a mouse model of metastatic melanoma. We found that relative to wild-type (WT) mice, Fat-1 mice exhibited fewer pulmonary metastatic colonies and improved inflammatory indices, including reduced serum tumor necrosis factor alpha (TNF-α) levels and pulmonary myeloperoxidase activity. Differential PUFA metabolites in serum were considered a key factor to alter cancer cell travelling to lung, and we found that n-6 PUFAs such as arachidonic acid induced CXCR4 protein expression although n-3 PUFAs such as eicosapentaenoic acid (EPA) decreased CXCR4 levels. In addition, serum levels of the bioactive EPA metabolite, 18-HEPE, were elevated in Fat-1 mice relative to WT mice, and 18-HEPE suppressed CXCR4 expression in B16-F0 cells. Moreover, relative to controls, numbers of pulmonary metastatic colonies were reduced in WT mice receiving intravenous injections either of 18-HEPE or 18-HEPE-pretreated melanoma cells. Our results indicate that 18-HEPE is a potential anticancer metabolite that mediates, at least in part, the preventive effect of n-3 PUFA on melanoma metastasis.

The current system of food production is linked to both the increasing prevalence of chronic disease and the deterioration of the environment, and thereby calls for novel ways of producing nutritious foods in a sustainable manner. In the "longevity village" of Bama, China, we have identified two plant foods, hemp seed and bitter vegetable (Sonchus oleraceus), that are commonly consumed by its residents and grow abundantly in unfarmed land without fertilizers or pesticides. Here, we show that a diet composed of these two foods (the "HB diet") provides a sufficient variety of nutrients and confers significant health benefits. Aged mice allowed ad libitum access to the HB diet not only had longer life spans and improved cognitive function but were also protected against age-related metabolic syndrome, fatty liver, gut dysbiosis and chronic inflammation compared to aged mice fed a control Western diet. Furthermore, longevity-related genes (including 5'adenosine monophosphate-activated protein kinase, sirtuin 1, nuclear respiratory factor 1 and forkhead box O3) were significantly up-regulated, while aging-related genes (including mammalian target of rapamycin and nuclear factor kappa B) were down-regulated. These results demonstrate that the HB diet is capable of promoting health and longevity, and present a sustainable source of healthy foods that can help control the prevalence of chronic diseases and reduce agricultural impact on the environment.

To investigate the metabolic regulation against oxygen supply, comparative metabolomics was performed to explore the metabolic responses of Mortierella alpina in the process of arachidonic acid (ARA) production. More than 110 metabolites involved in Embden–Meyerhof–Parnas pathway, pentose phosphate pathway, tricarboxylic acid cycle, inositol phosphate metabolism, fatty acid biosynthesis, and amino acid metabolism were identified by gas chromatography–mass spectrometry. Samples at different aeration rates were clearly distinguished by principal components analysis and partial least squares analysis, indicating that oxygen supply had a profound effect on the metabolism of M. alpina. Eleven major metabolites were identified as potential biomarkers to be primarily responsible for the difference of metabolism. Further study of metabolic changes with the relevant pathways demonstrated that the levels of several intermediate metabolites in relation to central carbon metabolism changed remarkably via both processes and citrate and malate was supposed to play vital roles in polyunsaturated acid (PUFA) synthesis. Increase of myo-inositol and sorbitol were probably for osmo-regulation and redox balance, while enhanced phosphoric acid and pyroglutamic acid were supposed to have function in the activation of signal transduction pathway for stress resistance. The present study provides a novel insight into the metabolic responses of M. alpina to aeration rates and the metabolic characteristics during the ARA fermentation.

Developing green and smart emulsifier for multiple responsive Pickering emulsion has been a great significance to many industries. Therefore, a novel emulsifier, poly (N-isopropylacrylamide) (PNIPAM) grafted chitosan (CS) microgel (CS-g-PNIPAM), was obtained, which exhibited swelling and deswelling behaviors in response to abrupt changes of pH and temperature. The resulting O/W Pickering emulsion was also sensitive to pH and temperature, and adjusting either the pH from 5.0 to 9.0 or temperature from 25 to 45 ℃ could effectively trigger oil-water separation and emulsification on demand. Based on it, a biphasic biocatalysis was applied to evaluate the catalytic capacity of this approach. The hydrolysis of fish oil and esterification of oleic acid with n-octanol were performed successfully. Meanwhile, the easy separation of products and good recyclability could be realized by reversibly increasing or decreasing temperature. The green system provides a great potential for the application of biopolymers in biphasic interfacial biocatalysis.

Background/aims Recent studies have found vitamin D deficiency promotes fat deposition into the hepatocytes, thus contributing to the development of nonalcoholic fatty liver disease (NAFLD), which is a hepatic manifestation of metabolic syndrome. This study aimed to investigate the potential effects of vitamin D on NAFLD with the involvement of the p53 pathway. Methods Initially, an in vivo high-fat diet (HFD)-induced NAFLD mouse model was established. Then the HFD-induced NAFLD mice were treated with vitamin D. Next, the serum levels of TNF-α, GSH-px and malondialdehyde (MDA) were assessed using ELISA and ROS content was evaluated by flow cytometry, followed by the measurement of expression of Duox1, Duox2, SOD1, SOD2, PRDX1 I, ACC, SREBP1c, MTTP, PPARα, p53, p21 and p16 using RT-qPCR and Western blot analysis. Positive expression of FAS and FASL proteins was measured using immunohistochemistry. TUNEL and Senescence-associated β-galactosidase (SA-β-Gal) staining were subsequently conducted to assess the senescence and apoptosis of hepatocytes. Results HFD-induced mice treated with vitamin D presented with significantly increased GSH-px levels, as well as protein expression of SOD1, SOD2, PRDX1, MTTP and PPARα, but decreased MDA and ROS levels, expression of Duox1, Duox2, ACC, SREBP1c, p53, p21 and p16, positive expression of FAS and FASL proteins as well as impaired senescence and apoptosis of hepatocytes. Conclusion Active vitamin D supplementation could potentially impede hepatocyte senescence and apoptosis via suppression of the p53 pathway, thus preventing the progression of NAFLD. Our study provides available evidence on the potential clinical utility of vitamin D supplementation in NAFLD.

Hyperglycemia significantly contributes to the development and progression of metabolic diseases. Managing postprandial blood glucose fluctuations is of particular importance for patients with hyperglycemia, but safe and effective means of reducing blood glucose levels are still lacking. Five diets with varying macronutrient ratios and omega-3 fatty acid amounts were tested for their blood glucose-lowering effects in male C57BL/6J mice. The diets with potent blood glucose-lowering effects were further investigated for their underlying mechanisms and their beneficial effects on hyperglycemia models. Mice given the low-carbohydrate, high-protein, and high-omega-3 (LCHP+3) diet exhibited a rapid reduction of the blood glucose levels that remained consistently low, regardless of feeding. These effects were associated with reduced amino acid gluconeogenesis, due to the inhibition of hepatic alanine transaminase (ALT). Furthermore, the LCHP+3 intervention was effective in reducing the blood glucose levels in several disease conditions, including type 1 diabetes mellitus, hormone-induced hyperglycemia, and diet-induced metabolic syndrome. Our findings identify the LCHP+3 diet as a potent blood glucose-lowering diet that suppresses postprandial blood glucose fluctuations through the inhibition of gluconeogenesis and may have great clinical utility for the management of metabolic diseases with hyperglycemia.

Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of liver damage characterized by abnormal hepatic fat accumulation and inflammatory response. Although the molecular mechanisms responsible for the disease are not yet fully understood, the pathogenesis of NAFLD likely involves multiple signals. The identification of effective therapeutic strategies to target these signals is of utmost importance. Carnosic acid (CA), as a phenolic diterpene with anticancer, anti-bacterial, anti-diabetic and neuroprotective properties, is produced by many species of the Lamiaceae family. Myristoylated alanine-rich C-kinase substrate (MARCKS) is a major protein kinase C (PKC) substrate in many different cell types. In the present study, wild-type C57BL/6 and MARCKS-deficient mice were randomly divided into the normal chow- or high-fat (HF) diet-fed groups. The HF diet increased the fasting glucose and insulin levels, and promoted glucose intolerance in the wild-type mice. MARCKS deficiency further upregulated intolerance, fasting glucose and insulin. The HF diet also promoted hepatic steatosis, serum alanine transaminase (ALT) and aspartate transaminase (AST) activity, inflammation and lipid accumulation in the wild-type mice. These responses were accelerated in the MARCKS-deficient mice. Importantly, increased inflammation and lipid accumulation were associated with phosphoinositide 3-kinase (PI3K)/AKT, NLR family pyrin domain containing 3 (NLRP3)/nuclear factor-κB (NF-κB) and sterol regulatory element binding protein-1c (SREBP-1c) signaling pathway activation. The mice treated with CA exhibited a significantly improved glucose and insulin tolerance. The production of pro-inflammatory cytokines and lipid accumulation were suppressed by CA. Significantly, MARCKS was reduced in mice fed the HF diet. CA treatment upregulated MARCKS expression compared to the HF group. Furthermore, the activation of the PI3K/AKT, NLRP3/NF-κB and SREBP-1c signaling pathways was inhibited by CA. Taken together, our data suggest that CA suppresses inflammation and lipogenesis in mice fed a HF diet through MARCKS regulation. Thus, CA may be prove to be a useful anti-NAFLD agent.

A novel double-walled microsphere composed of chitosan, sodium cellulose sulfate (NaCS) and sodium tripolyphosphate (TPP) was prepared. TPP was used as ionic crosslinker. The morphology of the microspheres was observed by microscope and SEM, and the results showed that the double-walled microsphere was smooth outside, with rough interior surface. FTIR spectra analysis was performed to investigate the PEC formation among chitosan, NaCS, and TPP. In vitro release studies of BSA showed that the double-walled microspheres had regular and sustainable release profiles in simulated colonic fluid (SCF). Our results indicated that the double-walled microspheres prepared could be used as a candidate protein drug carrier for the colon.

Bacterial endotoxin lipopolysaccharide (LPS)-induced sepsis is a critical medical condition, characterized by a severe systemic inflammation and rapid loss of muscle mass. Preventive and therapeutic strategies for this complex disease are still lacking. Here, we evaluated the effect of omega-3 (n-3) polyunsaturated fatty acid (PUFA) intervention on LPS-challenged mice with respect to inflammation, body weight and the expression of Toll-like receptor 4 (TLR4) pathway components. LPS administration induced a dramatic loss of body weight within two days. Treatment with n-3 PUFA not only stopped loss of body weight but also gradually reversed it back to baseline levels within one week. Accordingly, the animals treated with n-3 PUFA exhibited markedly lower levels of inflammatory cytokines or markers in plasma and tissues, as well as down-regulation of TLR4 pathway components compared to animals without n-3 PUFA treatment or those treated with omega-6 PUFA. Our data demonstrate that n-3 PUFA intervention can suppress LPS-induced inflammation and weight loss via, at least in part, down-regulation of pro-inflammatory targets of the TLR4 signaling pathway, and highlight the therapeutic potential of n-3 PUFA in the management of sepsis.

To monitor the current HIV prevalence, related risk behaviors and factors for HIV infection among the elderly male clients of the commercial female sex-workers (CFSW)in Guangxi.Face to face interview on male clients aged ≥40 years old was carried out in April to July, 2012. Information on demography, awareness of HIV prevention, related risk behaviors, history on HIV testing etc. were collected, with 3-5 ml full blood collected for testing on HIV. Data was analyzed by SPSS 18.0 software.4260 clients were surveyed at 14 surveillance sites in which 82.1% had received secondary or lower education, 72.0% experienced commercial sex in places with low-class sex trade. HIV awareness rate of clients was 74.2% in which the rate of clients who were HIV positive was 65.8%. Among all the clients, 73 were detected as HIV positive, with the HIV positive rate as 1.40% . Samples from voluntary counseling and testing sites showed higher risk to HIV infection than from other sources (OR = 23.672, 95%CI:4.984-112.434). Samples from middle class population showed lower risk to HIV infection than those at low class (OR = 0.410, 95%CI:0.190-0.885). Among those who were syphilis negative (OR = 0.255, 95%CI: 0.132-0.491) or hepatitis C virus (HCV)negative (OR = 0.154, 95% CI:0.059-0.401), the risk of getting HIV infected seemed to be low. Rate on condom use was low for clients among all of the sex-related behaviors regardless of the marriage status. In those lower-class sex trade places, lower rate on the condom use was seen. Rate for previous HIV testing for clients was only 4.6% . Among 41 clients who had received CD4 testing, 80.5% of them showed CD4 under 350 cell/µl, 61.0% were under 200 cell/µl.The HIV positive rate for elderly male clients of the CFSWs was high in Guangxi. Unprotective sexual contact with low class sex workers was the most important risk factor for HIV infection.

A novel spectrofluorimetric method has been proposed for the determination of nucleic acids based on shifting the dimer–monomer equilibrium of the fluorescent dye, acridine yellow (AY). Induced by the premicellar aggregation of an anionic surfactant, sodium dodecyl sulphate (SDS), AY formed a nonfluorescent homodimer (AYAY) which largely quenches the fluorescence intensity of the dimer system. However, the fluorescence intensity of the system increased dramatically when nucleic acids were added to the solution. The fluorescence enhancement is probably based on the DNA modulated shift of the dimer–monomer equilibrium of AY in the anionic surfactant solution. Intercalation of the monomer in DNA caused the dissociation of AYAY, and led a very high fluorescence enhancement. A linear dependence of fluorescence intensity on Calf thymus (CT) DNA concentration over the rang of 0∼40 μg/ml CT DNA allowed sensitive quantification of CT DNA by a simple fluorescent method. The detection limit was 0.023 μg/ml and the RSD was 1.5% for 2 μg/ml CT DNA ( n =7). Furthermore, calibration graphs for yeast RNA, polynucleotides, such as poly (A) and poly (I) were also obtained.

To develop and preliminarily evaluate two immunodiagnostic methods for clonorchiasis using Clonorchis sinensis PPMP I antigen Cs2 recombinant protein (rCs2).Using the soluble rCs2, an indirect ELISA and a colloidal-gold immuno-chromatography assay (GICA) dynamic flow strip was developed for detecting specific antibodies in serum. Serum samples from 35 egg-positive clonorchiasis patients, 33 healthy individuals, 15 schistosomiasis patients, 15 paragonimiasis westermani patients and 13 cysticercosis patients were examined by ELISA and GICA strip test. To further evaluate the diagnostic value of these two methods, eight New Zealand rabbits were randomly divided into infected group and treatment group. Each rabbit was infected with 600 C. sinensis metacercaria. Rabbits in treatment group were treated with praziquantel [150 mg/(kg x d) x 2d] individually at day 56 post-infection. ELISA and GICA strip test were used to observe the dynamic changes of specific antibodies against rCs2 in the two parallel groups during the period of 0-44 weeks.The sensitivity, specificity and total coincidence rate determined by the ELISA method were 71.4% (25/35), 93.4% (71/76), and 86.5% (96/111), respectively, and the cross reaction with schistosomiasis, paragonimiasis and cysticercosis patients were 1/15, 1/15, and 1/13, respectively. The sensitivity, specificity and coincidence rate in the GICA strip test were 85.7% (30/35), 92.1% (70/76), and 90.1%(100/111), respectively. In C sinensis infected rabbits, antibodies level began to increase at 4 weeks after infection, peaked at the 6th week, and declined rapidly to a lower level in the 20th week, while the changing pattern of antibodies level in the treatment group was similar with that of infected group (P0.05). In the GICA strip test, antibodies in two groups could be detected in 4-16 weeks.Indirect ELISA and the GICA dynamic flow strip developed in this study may be of value in the immunodiagnosis of clonorchiasis.

To explore the relationship between plasma homocysteine levels and diabetic peripheral neuropathy (DPNP).A crossectional analysis was conducted on 227 patients with type 2 diabetes. Peripheral neuropathy was confirmed using electromyography (EMG). The risk factors possibly associated with diabetic neuropathy or plasma homocysteine levels were analyzed in relation to likelihood of occurrence of DPNP.Eighty patients with neuropathy and 147 patients without neuropathy were included. Plasma homocysteine levels were significantly higher in patients with diabetic neuropathy [(12.6 ± 3.6) µmol/L] than without diabetic neuropathy [(8.2 ± 0.9) µmol/L] (P0.001), and the relationship remained significant after adjusting for duration of diabetes, glycosylated hemoglobin A1c (HbA1c), age, renal status, serum folate acid and vitamin B(12), and metformin [OR 1.15 (1.02 - 1.28), P0.05]. In addition, per increase of 4.0 µmol/L plasma homocysteine was closely related to the occurrence of neuropathy after controlling for per unit increase of other confounding factors [OR 1.17 (0.94 - 1.33), P0.05].Hyperhomocysteinemia was an independent risk factor for the occurrence of diabetic peripheral neuropathy.