Epidemiologic and preclinical studieshave shown that marine n‐3 polyunsaturated fatty acids (n‐3 PUFAs) elicit promising chemoprevention against breast cancer. Docosahexaenoic acid monoglyceride ...(MAG‐DHA), a docosahexaenoic acid sn‐1‐monoacylglycerol does not required pancreatic lipase to be absorbed, eliciting a better bioavailability when compared with other formulations such as DHA‐free fatty acid, DHA‐triglycerol, or DHA‐ethyl ester. However, the anticancer actions and underlying mechanisms of MAG‐DHA on breast cancer remain to be assessed. In this study, MAG‐DHA induced significant growth inhibition in MCF‐7 and MDA‐MB‐231 breast cancer cells in a dose‐dependent manner. MAG‐DHA treatment (80 µM) led to 83.8 and 94.3% growth inhibition between MCF‐7 and MDA‐MB‐231 cells, respectively. MAG‐DHA‐induced growth inhibition was tightly associated with apoptosis, as evidenced by increased active forms of caspase‐3, poly (ADP‐ribose) polymerase (PARP) and caspase‐12. In particular, MAG‐DHA‐induced apoptosis was triggered by oxidative stress‐mediated endoplasmic reticulum (ER) stress, as evidenced by activation of the PERK‐eIF2α pathway in ER. MAG‐DHA treatment also strongly suppressed the growth of E0771 murine breast cancer xenografts, significant differences of tumor volume were found between MAG‐DHA group (0.271 cm3) and control group (0.875 cm3) after 15 daily MAG‐DHA treatments. The in vitro antibreast cancer mechanism of MAG‐DHA was supported by the in vivo xenograft model. In addition, MAG‐DHA‐induced ER stress concomitantly triggered autophagy in these cancer cells, and the induction of autophagy suppressed its ability to induce apoptotic cell death. Our data suggested that MAG‐DHA as dietary supplement, in combination with autophagy inhibitors may be a useful therapeutic strategy in treating breast cancer.
High-fat (HF) diets and low-grade chronic inflammation contribute to the development of insulin resistance and type 2 diabetes (T2D), whereas n-3 polyunsaturated fatty acids (PUFAs), due to their ...anti-inflammatory effects, protect against insulin resistance. Interleukin (IL)-1β is implicated in insulin resistance, yet how n-3 PUFAs modulate IL-1β secretion and attenuate HF diet-induced insulin resistance remains elusive. In this study, a HF diet activated NLRP3 inflammasome via inducing reactive oxygen species (ROS) generation and promoted IL-1β production primarily from adipose tissue preadipocytes, but not from adipocytes and induced insulin resistance in wild type (WT) mice. Interestingly, endogenous synthesized n-3 polyunsaturated fatty acids (PUFAs) reversed this process in HF diet-fed fat-1 transgenic mice although the HF diet induced higher weight gain in fat-1 mice, compared with the control diet. Mechanistically, palmitic acid (PA), the main saturated fatty acid in an HF diet inactivated AMPK and led to decreased GSK-3β phosphorylation, at least partially through reducing Akt activity, which ultimately blocked the Nrf2/Trx1 antioxidant pathway and induced TXNIP cytoplasm translocation and NLRP3 inflammasome activation, whereas docosahexaenoic acid (DHA), the most abundant n-3 PUFA in fat-1 adipose tissue, reversed this process via inducing Akt activation. Our
shRNA knockdown study further revealed that GSK-3β played a pivot role between the upstream AMPK/Akt pathway and downstream Nrf2/Trx1/TXNIP pathway. Given that NLRP3 inflammasome is implicated in the development of most inflammatory diseases, our results suggest the potential of n-3 PUFAs in the prevention or adjuvant treatment of NLRP3 inflammasome-driven diseases.
Wines from different regions have different qualities due to the impact of geographical location and climate. The sale of inferior wines seriously violates the fair-trade rights of consumers. This ...article provides an elemental analysis classification method for verifying the geographical origin of wines in the People's Republic of China. Inductively coupled plasma mass spectrometry, liquid chromatography isotope ratio mass spectrometry, and an isotope ratio mass spectrometer were used to analyze 142 wine samples collected from Helan Mountain, Xinjiang, Yunchuanzang, the Yanhuai Valley, and the Hexi Corridor regions. The data included elemental profiles, carbon isotope ratios (δ13C), and oxygen isotope ratios (δ18O). The results of multivariate analysis revealed that the geographical origin of wine is closely related to variations in elemental profiles and isotope ratios. Introducing δ18O and the elements Li, Mn, Ag, In, Th, Ta, and Re into the discriminant model yielded correct classification rates of the linear discriminant model of 90.8% for the training set and 87.3% for the test set.
The concentrations of trace elements in wines and health risk assessment via wine consumption were investigated in 315 wines. Samples were collected from eight major wine-producing regions in China. ...The concentrations of twelve trace elements were determined by inductively coupled plasma mass spectrometry (ICP-MS) and Duncan's multiple range test was applied to analyze significant variations (
< 0.05) of trace elements in different regions. Based on a 60 kg adult drinker consuming 200 mL of wine per day, the estimated daily intake (EDI) of each element from wines was far below the provisional tolerable daily intake (PTDI). Health risk assessment indicated the ingestion influence of individual elements and combined elements through this Chinese wine daily intake did not constitute a health hazard to people. However, Cr and Mn were the potential contaminants of higher health risk in Chinese wines. The cumulative impact of wine consumption on trace elements intake in the daily diet of drinkers should not be ignored due to the presence of other intake pathways.
Summary
Aims
Fatigue is a common burdensome problem in patients with Parkinson's disease (PD), but its pathophysiological mechanisms are poorly understood. This study aimed at investigating the ...neural substrates of fatigue in patients with PD.
Methods
A total of 17 PD patients with fatigue, 32 PD patients without fatigue, and 25 matched healthy controls were recruited. The 9‐item fatigue severity scale (FSS) was used for fatigue screening and severity rating. Resting‐state functional magnetic resonance imaging (RS‐fMRI) data were obtained from all subjects. Amplitude of low‐frequency fluctuations (ALFF) was used to measure regional brain activity, and functional connectivity (FC) was applied to investigate functional connectivity at a network level.
Results
PD‐related fatigue was associated with ALFF changes in right middle frontal gyrus within the attention network and in left insula as well as right midcingulate cortex within the salience network. FC analysis revealed that above three regions showing ALFF differences had altered functional connectivity mainly in the temporal, parietal, and motor cortices.
Conclusion
Our findings do reveal that abnormal regional brain activity within attention and salience network and altered FC of above abnormal regions are involved in neural mechanism of fatigue in patients with PD.
Oxidative stress (OS) is a crucial factor influencing the development of Parkinson’s disease (PD). Here we first reported that Lindleyin (Lin), one of the major components of rhubarb, possessed ...neuroprotective effects against H2O2-induced SH-SY5Y cell injury and MPTP-induced PD of C57BL/6 mice. The results showed that Lin can decrease cell death and apoptotic rate induced by H2O2 through inhibiting mitochondrial apoptotic pathway and increasing the activities of SOD, GSH-Px, and CAT as well as decreasing the level of MDA. In addition, in vivo studies showed that oral administration of Lin (5 or 20 mg/kg) showed significant change in motor function deficits, antioxidant enzyme activities, apoptotic pathway, and tyrosine hydroxylase expression. Our results reveal that Lin might be a promising anti-PD agent by reducing OS and apoptosis.
Melanoma is a malignant tumor that arises from epidermal melanocytes with high morbidity and mortality, and currently, there are no effective conventional genotoxic treatments or systematic ...treatment. Increasing evidence shows that n-3 polyunsaturated fatty acids (PUFAs) exhibit anti-melanoma activity, but their anti-melanoma mechanism remains elusive. Here, C57BL/6 mice were injected with B16F10 melanoma cells
via
a tail vein to establish a lung metastasis model. n-3 PUFAs were significantly increased in lung metastatic tissues from mice treated with algal oil, especially rich in docosahexaenoic acid (DHA). Algal oil treatment significantly suppressed pulmonary metastases and outgrowth of melanoma cells, which was associated with autophagy induction, as evidenced by an increase in LC3-II levels. In addition, algae oil-triggered autophagy was mediated by inactivation of the mammalian target of rapamycin (mTOR) and p38 mitogen-activated protein (MAP) kinase, and activation of c-Jun N-terminal kinases (JNKs), which led to a decrease in p62 accumulation and decreased secretion of proinflammatory cytokine interleukin-1β (IL-1β). These results suggest that algal oil exerts its antitumourigenic activities
via
autophagy-mediated p62 elimination and anti-inflammatory properties.
Melanoma is a malignant tumor that arises from epidermal melanocytes with high morbidity and mortality, and currently, there are no effective conventional genotoxic treatments or systematic treatment.
Aquatic animals are frequently suffered from starvation due to restricted food availability or deprivation. It is currently known that gut microbiota assists host in nutrient acquisition. Thus, ...exploring the gut microbiota responses would improve our understanding on physiological adaptation to starvation. To achieve this, we investigated how the gut microbiota and shrimp digestion and immune activities were affected under starvation stress. The results showed that the measured digestion activities in starved shrimp were significantly lower than in normal cohorts; while the measured immune activities exhibited an opposite trend. A structural equation modeling (SEM) revealed that changes in the gut bacterial community were directly related to digestive and immune enzyme activities, which in turn markedly affected shrimp growth traits. Notably, several gut bacterial indicators that characterized the shrimp nutrient status were identified, with more abundant opportunistic pathogens in starved shrimp, although there were no statistical differences in the overall diversity and the structures of gut bacterial communities between starved and normal shrimp. Starved shrimp exhibited less connected and cooperative interspecies interaction as compared with normal cohorts. Additionally, the functional pathways involved in carbohydrate and protein digestion, glycan biosynthesis, lipid and enzyme metabolism remarkably decreased in starved shrimp. These attenuations could increase the susceptibility of starved shrimp to pathogens infection. In summary, this study provides novel insights into the interplay among shrimp digestion, immune activities and gut microbiota in response to starvation stress.
•Shrimp immunity is compromised under starvation.•Gut microbiota affects shrimp growth traits.•Starved shrimp are susceptible to infection.
Stress induced by ultraviolet-B (UV-B) irradiation stimulates the accumulation of various secondary metabolites in plants. Nitric oxide (NO) serves as an important secondary messenger in UV-B ...stress-induced signal transduction pathways. NO can be synthesized in plants by either enzymatic catalysis or an inorganic nitrogen pathway. The effects of UV-B irradiation on the production of baicalin and the associated molecular pathways in plant cells are poorly understood. In this study, nitric oxide synthase (NOS) activity, NO release and the generation of baicalin were investigated in cell suspension cultures of Scutellaria baicalensis exposed to UV-B irradiation. UV-B irradiation significantly increased NOS activity, NO release and baicalin biosynthesis in S. baicalensis cells. Additionally, exogenous NO supplied by the NO donor, sodium nitroprusside (SNP), led to a similar increase in the baicalin content as the UV-B treatment. The NOS inhibitor, Nω-nitro-l-arginine (LNNA), and NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) partially inhibited UV-B-induced NO release and baicalin accumulation. These results suggest that NO is generated by NOS or NOS-like enzymes and plays an important role in baicalin biosynthesis as part of the defense response of S. baicalensis cells to UV-B irradiation.
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•Streptozocin-induced hyperglycemia led to renal dysfunctions and renal injury, which were attenuated by endogenous n-3 PUFAs in fat-1 transgenic mice.•The renoprotective effects of ...endogenous n-3 PUFAs against DN were linked with the production of n-3 lipid mediators, increased expression of E-cadherin and NLRP3 inflammasome inhibition in renal tissues.
Although n-3 polyunsaturated fatty acids (PUFAs) exhibit biological activity in many inflammatory diseases, their renoprotective effects against diabetic nephropathy (DN) have been controversial. Here, fat-1 transgenic mice were used to investigate the effects of n-3 PUFAs on streptozocin (STZ)-induced DN. Fat-1 mice exhibited increased renal n-3 PUFAs and n-3 PUFA-derived lipid mediators, compared to wild type (WT) mice. Endogenous n-3 PUFAs protected STZ-treated fat-1 mice against hyperglycemia-induced renal dysfunction, as reflected by significant decreases in kidney/body weight ratio, urinary protein, blood urea nitrogen levels and creatinine clearance. In addition, endogenous n-3 PUFAs significantly ameliorated hyperglycemia-induced renal damage by modulating E-cadhein expression. It was also found that DN-induced NLRP3 inflammasome activation was attenuated by endogenous n-3 PUFAs in STZ-treated fat-1 mice. Our findings suggest that endogenous n-3 PUFAs ameliorate DN potentially through the: (i) formation of n-3 lipid mediators, (ii) induction of E-cadherin expression and (iii) inhibition of NLRP3 inflammasome.
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