Effect of moxibustion on the SIRT1/FOXO3a signaling pathway in ApoE-/- mice with atherosclerosis. / 艾灸对ApoE-/-åŠ¨è„‰ç²¥æ ·ç¡¬åŒ–å°é¼ SIRT1/FOXO3a信号通路的影响.

OBJECTIVES: To observe the effects of moxibustion on blood lipid metabolism, pathological morphology of thoracic aorta, and the expression of silent information regulator 1 (SIRT1) and forkhead box transcription factor O3a (FOXO3a) in ApoE-/- atherosclerosis (AS) mice, so as to explore the potential mechanism of moxibustion in preventing and treating AS. METHODS: Ten C57BL/6J mice were fed a normal diet as the control group, and 30 ApoE-/- mice were fed a high-fat diet to establish the AS model, which were randomly divided into the model group, simvastatin group, and moxibustion group, with 10 mice in each group. From the first day of modeling, mice in the moxibustion group received mild moxibustion treatment at "Shenque"(CV8), "Yinlingquan"(SP9), bilateral "Neiguan"(PC6) and "Xuehai"(SP10) for 30 min per time；the mice in the simvastatin group were given simvastatin orally (2.5 mg·kg-1·d-1), with both treatments given once daily, 5 times a week, with a total intervention period of 12 weeks. The body weight and general condition of the mice were observed and recorded during the intervention period. After the intervention, the contents of serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured using an automated biochemistry analyzer. Hematoxylin eosin (HE) staining was used to observe the pathological morphology of the thoracic aorta. ELISA was used to measure the contents of serum oxidized low-density lipoprotein (ox-LDL) and superoxide dismutase (SOD) activity. Western blot and real-time fluorescent quantitative PCR analysis were used to detect the expression levels of SIRT1 and FOXO3a protein and mRNA in the thoracic aorta. RESULTS: Compared with the control group, body weight at the 8th and 12th week, serum TC, TG, LDL-C, and ox-LDL contents of the model group mice were significantly increased(P<0.05, P<0.01), while the HDL-C contents, SOD activity, and the expression levels of SIRT1 protein and mRNA in the thoracic aorta were significantly decreased(P<0.05, P<0.01). HE staining showed thickening of the aortic intima, endothelial cell degeneration, swelling, and shedding. Compared with the model group, body weight at the 8th and 12th week, serum TC, TG, LDL-C, and ox-LDL contents of mice in the simvastatin group and moxibustion group were significantly decreased(P<0.01), while the serum SOD activity, expression levels of SIRT1 protein and mRNA in the thoracic aorta were significantly increased(P<0.01). The HDL-C contents were significantly increased in the simvastatin group(P<0.05). The thoracic aortic structure was more intact in both groups, with a more regular lumen and orderly arrangement of the elastic membrane in the media, and a slight amount of endothelial cell degeneration and swelling in the intima. There was no significant difference in the evaluated indexes between the moxibustion group and the simvastatin group and the pathological changes in the thoracic aorta were similar between the two groups. CONCLUSIONS: Moxibustion can reduce the body weight of AS model mice, regulate lipid levels, repair vascular intima, and alleviate endothelial damage. Its mechanism of action may be related to the regulation of the SIRT1/FOXO3a signaling pathway to improve oxidative damage.

Selective transcriptomic dysregulation of metabolic pathways in liver and retina by short- and long-term dietary hyperglycemia.

A high glycemic index (HGI) diet induces hyperglycemia, a risk factor for diseases affecting multiple organ systems. Here, we evaluated tissue-specific adaptations in the liver and retina after feeding HGI diet to mice for 1 or 12 month. In the liver, genes associated with inflammation and fatty acid metabolism were altered within 1 month of HGI diet, whereas 12-month HGI diet-fed group showed dysregulated expression of cytochrome P450 genes and overexpression of lipogenic factors including Srebf1 and Elovl5. In contrast, retinal transcriptome exhibited HGI-related notable alterations in energy metabolism genes only after 12 months. Liver fatty acid profiles in HGI group revealed higher levels of monounsaturated and lower levels of saturated and polyunsaturated fatty acids. Additionally, HGI diet increased blood low-density lipoprotein, and diet-aging interactions affected expression of mitochondrial oxidative phosphorylation genes in the liver and disease-associated genes in retina. Thus, our findings provide new insights into retinal and hepatic adaptive mechanisms to dietary hyperglycemia.

Dietary fish oil enriched in very-long-chain polyunsaturated fatty acid reduces cardiometabolic risk factors and improves retinal function.

Very-long-chain polyunsaturated fatty acids (VLCPUFAs; C24-38) constitute a unique class of PUFA that have important biological roles, but the lack of a suitable dietary source has limited research in this field. We produced an n-3 C24-28-rich VLCPUFA-oil concentrated from fish oil to study its bioavailability and physiological functions in C57BL/6J mice. The serum and retinal C24:5 levels increased significantly compared to control after a single-dose gavage, and VLCPUFAs were incorporated into the liver, brain, and eyes after 8-week supplementation. Dietary VLCPUFAs resulted in favorable cardiometabolic changes, and improved electroretinography responses and visual performance. VLCPUFA supplementation changed the expression of genes involved in PPAR signaling pathways. Further in vitro studies demonstrated that the VLCPUFA-oil and chemically synthesized C24:5 are potent agonists for PPARs. The multiple potential beneficial effects of fish oil-derived VLCPUFAs on cardiometabolic risk and eye health in mice support future efforts to develop VLCPUFA-oil into a supplemental therapy.

Pterostilbene alleviated cerebral ischemia/reperfusion-induced blood-brain barrier dysfunction via inhibiting early endothelial cytoskeleton reorganization and late basement membrane degradation.

Pterostilbene, an important analogue of the star molecule resveratrol and a novel compound naturally occurring in blueberries and grapes, exerts a significant neuroprotective effect on cerebral ischemia/reperfusion (I/R), but its mechanism is still unclear. This study aimed to follow the molecular mechanisms behind the potential protective effect of pterostilbene against I/R induced injury. For fulfilment of our aim, we investigated the protective effects of pterostilbene on I/R injury caused by middle cerebral artery occlusion (MCAO) in vivo and oxygen-glucose deprivation (OGD) in vitro. Machine learning models and molecular docking were used for target exploration and validated by western blotting. Pterostilbene significantly reduced the cerebral infarction volume, improved neurological deficits, increased cerebral microcirculation and improved blood-brain barrier (BBB) leakage. Machine learning models confirmed that the stroke target MMP-9 bound to pterostilbene, and molecular docking demonstrated the strong binding activity. We further found that pterostilbene could depolymerize stress fibers and maintain the cytoskeleton by effectively increasing the expression of the non-phosphorylated actin depolymerizing factor (ADF) in the early stage of I/R. In the late stage of I/R, pterostilbene could activate the Wnt pathway and inhibit the expression of MMP-9 to decrease the degradation of the extracellular basement membrane (BM) and increase the expression of junction proteins. In this study, we explored the protective mechanisms of pterostilbene in terms of both endothelial cytoskeleton and extracellular matrix. The early and late protective effects jointly maintain BBB stability and attenuate I/R injury, showing its potential to be a promising drug candidate for the treatment of ischemic stroke.

Gastrodin ameliorates cognitive dysfunction in diabetes by inhibiting PAK2 phosphorylation.

Diabetes is associated with higher prevalence of cognitive dysfunction, while the underlying mechanism is still elusive. In this study, we aim to explore the potential mechanism of diabetes-induced cognitive dysfunction and assess the therapeutic effects of Gastrodin on cognitive dysfunction. Diabetes was induced by a single injection of streptozotocin. The Morris Water Maze Test was employed to assess the functions of spatial learning and memory. Transcriptome was used to identify the potential factors involved. Western blot and immunofluorescence were applied to detect the protein expression. Our results have shown that spatial learning was impaired in diabetic rats, coupled with damaged hippocampal pyramidal neurons. Gastrodin intervention ameliorated the spatial learning impairments and neuronal damages. Transcriptomics analysis identified differential expression genes critical for diabetes-induced hippocampal damage and Gastrodin treatment, which were further confirmed by qPCR and western blot. Moreover, p21 activated kinase 2 (PAK2) was found to be important for diabetes-induced hippocampal injury and its inhibitor could promote the survival of primary hippocampal neurons. It suggested that PAK2 pathway may be involved in cognitive dysfunction in diabetes and could be a therapeutic target for Gastrodin intervention.

Signaling mechanisms in renal compensatory hypertrophy revealed by multi-omics.

Loss of a kidney results in compensatory growth of the remaining kidney, a phenomenon of considerable clinical importance. However, the mechanisms involved are largely unknown. Here, we use a multi-omic approach in a unilateral nephrectomy model in male mice to identify signaling processes associated with renal compensatory hypertrophy, demonstrating that the lipid-activated transcription factor peroxisome proliferator-activated receptor alpha (PPARα) is an important determinant of proximal tubule cell size and is a likely mediator of compensatory proximal tubule hypertrophy.

Comparison of the dietary omega-3 fatty acids impact on murine psoriasis-like skin inflammation and associated lipid dysfunction.

Persistent skin inflammation and impaired resolution are the main contributors to psoriasis and associated cardiometabolic complications. Omega-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), are known to exert beneficial effects on inflammatory response and lipid function. However, a specific role of omega-3 PUFAs in psoriasis and accompanied pathologies are still a matter of debate. Here, we carried out a direct comparison between EPA and DHA 12 weeks diet intervention treatment of psoriasis-like skin inflammation in the K14-Rac1V12 mouse model. By utilizing sensitive techniques, we targeted EPA- and DHA-derived specialized pro-resolving lipid mediators and identified tightly connected signaling pathways by RNA sequencing. Treatment with experimental diets significantly decreased circulating pro-inflammatory cytokines and bioactive lipid mediators, altered psoriasis macrophage phenotypes and genes of lipid oxidation. The superficial role of these changes was related to DHA treatment and included increased levels of resolvin D5, protectin DX and maresin 2 in the skin. EPA treated mice had less pronounced effects but demonstrated a decreased skin accumulation of prostaglandin E2 and thromboxane B2. These results indicate that modulating psoriasis skin inflammation with the omega-3 PUFAs may have clinical significance and DHA treatment might be considered over EPA in this specific disease.

Attenuation of Epileptogenesis and Cognitive Deficits by a Selective and Potent Kv7 Channel Opener in Rodent Models of Seizures.

Targeting neuronal Kv7 channels by pharmacological activation has been proven to be an attractive therapeutic strategy for epilepsy. Here, we show that activation of Kv7 channels by an opener SCR2682 dose-dependently reduces seizure activity and severity in rodent models of epilepsy induced by a GABAa receptor antagonist pentylenetetrazole (PTZ), maximal electroshock, and a glutamate receptor agonist kainic acid (KA). Electroencephalographic recordings of rat cerebral cortex confirm that SCR2682 also decreases epileptiform discharges in KA-induced seizures. Nissl and neuronal nuclei staining further demonstrates that SCR2682 also protects neurons from injury induced by KA. In Morris water maze navigation and Y-maze tests, SCR2682 improves PTZ- and KA-induced cognitive impairment. Taken together, our findings demonstrate that pharmacological activation of Kv7 by novel opener SCR2682 may hold promise for therapy of epilepsy with cognitive impairment. SIGNIFICANCE STATEMENT: A neuronal Kv7 channel opener SCR2682 attenuates epileptogenesis and seizure-induced cognitive impairment in rodent models of seizures, thus possessing a developmental potential for effective therapy of epilepsy with cognitive impairment.

Purinergic receptors mediate endothelial dysfunction and participate in atherosclerosis.

Atherosclerosis is the main pathological basis of cardiovascular disease and involves damage to vascular endothelial cells (ECs) that results in endothelial dysfunction (ED). The vascular endothelium is the key to maintaining blood vessel health and homeostasis. ED is a complex pathological process involving inflammation, shear stress, vascular tone, adhesion of leukocytes to ECs, and platelet aggregation. The activation of P2X4, P2X7, and P2Y2 receptors regulates vascular tone in response to shear stress, while activation of the A2A, P2X4, P2X7, P2Y1, P2Y2, P2Y6, and P2Y12 receptors promotes the secretion of inflammatory cytokines. Finally, P2X1, P2Y1, and P2Y12 receptor activation regulates platelet activity. These purinergic receptors mediate ED and participate in atherosclerosis. In short, P2X4, P2X7, P2Y1, and P2Y12 receptors are potential therapeutic targets for atherosclerosis.

Differential Effect of Dietary Supplementation with a Soybean Oil Enriched in Oleic Acid versus Linoleic Acid on Plasma Lipids and Atherosclerosis in LDLR-Deficient Mice.

Both monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) play important roles in lipid metabolism, and diets enriched with either of these two fatty acids are associated with decreased cardiovascular risk. Conventional soybean oil (CSO), a common food ingredient, predominantly contains linoleic acid (LA; C18:2), a n-6 PUFA. Recently, a modified soybean oil (MSO) enriched in oleic acid (C18:1), a n-9 MUFA, has been developed, because of its improved chemical stability to oxidation. However, the effect of the different dietary soybean oils on cardiovascular disease remains unknown. To test whether diets rich in CSO versus MSO would attenuate atherosclerosis development, LDL receptor knock-out (LDLR-KO) mice were fed a Western diet enriched in saturated fatty acids (control), or a Western diet supplemented with 5% (w/w) LA-rich CSO or high-oleic MSO for 12 weeks. Both soybean oils contained a similar amount of linolenic acid (C18:3 n-3). The CSO diet decreased plasma lipid levels and the cholesterol content of VLDL and LDL by approximately 18% (p < 0.05), likely from increased hepatic levels of PUFA, which favorably regulated genes involved in cholesterol metabolism. The MSO diet, but not the CSO diet, suppressed atherosclerotic plaque size compared to the Western control diet (Control Western diet: 6.5 ± 0.9%; CSO diet: 6.4 ± 0.7%; MSO diet: 4.0 ± 0.5%) (p < 0.05), independent of plasma lipid level changes. The MSO diet also decreased the ratio of n-6/n-3 PUFA in the liver (Control Western diet: 4.5 ± 0.2; CSO diet: 6.1 ± 0.2; MSO diet: 2.9 ± 0.2) (p < 0.05), which correlated with favorable hepatic gene expression changes in lipid metabolism and markers of systemic inflammation. In conclusion, supplementation of the Western diet with MSO, but not CSO, reduced atherosclerosis development in LDLR-KO mice independent of changes in plasma lipids.

Mitochondrial C5aR1 activity in macrophages controls IL-1ß production underlying sterile inflammation.

While serum-circulating complement destroys invading pathogens, intracellularly active complement, termed the "complosome," functions as a vital orchestrator of cell-metabolic events underlying T cell effector responses. Whether intracellular complement is also nonredundant for the activity of myeloid immune cells is currently unknown. Here, we show that monocytes and macrophages constitutively express complement component (C) 5 and generate autocrine C5a via formation of an intracellular C5 convertase. Cholesterol crystal sensing by macrophages induced C5aR1 signaling on mitochondrial membranes, which shifted ATP production via reverse electron chain flux toward reactive oxygen species generation and anaerobic glycolysis to favor IL-1ß production, both at the transcriptional level and processing of pro­IL-1ß. Consequently, atherosclerosis-prone mice lacking macrophage-specific C5ar1 had ameliorated cardiovascular disease on a high-cholesterol diet. Conversely, inflammatory gene signatures and IL-1ß produced by cells in unstable atherosclerotic plaques of patients were normalized by a specific cell-permeable C5aR1 antagonist. Deficiency of the macrophage cell-autonomous C5 system also protected mice from crystal nephropathy mediated by folic acid. These data demonstrate the unexpected intracellular formation of a C5 convertase and identify C5aR1 as a direct modulator of mitochondrial function and inflammatory output from myeloid cells. Together, these findings suggest that the complosome is a contributor to the biologic processes underlying sterile inflammation and indicate that targeting this system could be beneficial in macrophage-dependent diseases, such as atherosclerosis.

L-Cysteine Increases the Transformation Efficiency of Chinese Cabbage (Brassica rapa ssp. pekinensis).

Successful Agrobacterium-mediated transformations of Chinese cabbage have been limited owing to the plant's recalcitrant nature, genomic background and explant necrosis upon infection, which hinders the transfer of T-DNA region into the Chinese cabbage. Consequently, in the current experiment, a stable Agrobacterium tumefaciens-mediated transformation method for Chinese cabbage cv. Kenshin established by employing important anti-oxidants in the co-cultivation and subsequent regeneration media. Four-day-old in vitro derived cotyledon explants were infected with A. tumefaciens strain GV3101 harboring the vector pCAMIBA1303. Cotyledon explants exposed to an Agrobacterium suspension (OD600 of approximately 0.6) for 10 min and then incubated for 3 days co-cultivation in Murashige and Skoog medium containing an L-cysteine + AgNO3 combination exhibited the highest ß-glucuronidase (GUS) expression (94%) and explant regeneration efficiency (76%). After 3 days, the cotyledon explants were subjected to three selection cycles with gradually increasing hygromycin B concentrations (10 to 12 mg/L). The incorporation and expression of hptII in T0 transformed plants were verified by polymerase chain reaction and Southern blot analyses. These transgenic plants (T0) were fertile and morphologically normal. Using the present protocol, a successful transformation efficiency of 14% was achieved, and this protocol can be applied for genome editing and functional studies to improve Chinese cabbage traits.

The Anatomy of the Temporal and Zygomatic Branches of the Facial Nerve: Application to Crow's Feet Wrinkles.

BACKGROUND: Advances in the understanding of wrinkling crow's feet while improving the safety and efficacy of botulinum toxin type A injection has pointed to drug dispersion in the lateral orbital wrinkles as a cause of adverse events of botulinum toxin type A injection. The purpose of this study is to identify the distribution of temporal and zygomatic branches of facial nerve in the orbicularis oculi muscles. METHODS: Anatomical dissection of cadavers was performed in 31 cadavers, 13 females and 18 males, with ages ranging from 20 to 60 years, which of all had been embalmed by 10% formalin solution. The facial nerve was identified within subcutaneous tissue close periorbital region and both traced proximal and distal. Its temporal branch, zygomatic branch, facial and muscular entrance were located and accurately measured relative to established surface landmarks. RESULTS: Dissection of the facial nerve revealed 2 to 6 entrances of the temporal branch into the orbicularis oculi and 1 to 5 entrances of the zygomatic branch into the orbicularis oculi. Concerning the measurements of neural entering points, distance and angle from orbicularis oculi muscle to lateral ocular angle, a distribution map of its muscular entrance and their patterns of distribution were constructed. According to the dense area of the coordinate map, there were 3 points determined as the muscular entrance points to established surface landmarks. CONCLUSIONS: An anatomical dissection of cadavers was performed to identify the distribution of temporal and zygomatic branches of the facial nerve in the orbicularis oculi. According to the dense area of the coordinate map, the surface landmarks of 3 points were established as the muscular entrance of the facial nerve (MEF).

Hypertriglyceridemia: new approaches in management and treatment.

PURPOSE OF REVIEW: Hypertriglyceridemia (HTG), a form of dyslipidemia characterized by elevated plasma of triglycerides (TG), is associated with an increased risk for acute pancreatitis. Moreover, HTG has recently been shown to be linked to the development of atherosclerotic cardiovascular disease (ASCVD); therefore, there is a great interest in better understanding the pathophysiology of HTG and improving its clinical management. In this review, we briefly describe TG metabolism, recent guidelines for the clinical management of HTG and provide an overview of the current and potential new therapies for HTG. RECENT FINDINGS: Screening patients for HTG is valuable for not only identifying patients with extreme TG elevations, who are at risk for pancreatitis, but also for managing ASCVD risk in patients with more moderate forms of HTG. Therefore, the most recent USA guidelines for cardiovascular diseases recommend using TG as a risk enhancer test, leading to a more aggressive treatment of patients with intermediate risk. Currently, there are several available approaches for reducing plasma TG, which include lifestyle changes, fibrates and omega-3 fatty acid treatment. The addition of eicosapentaenoic acid (EPA) on top of statins has recently been shown to significantly reduce ASCVD events. Nevertheless, there is an unmet need for more effective treatment options. Several new therapies based on newly identified targets in TG metabolism, such as apolipoprotein C-III and angiopoietin-like 3 protein, are currently under development. SUMMARY: The clinical management of HTG is important in the prevention and treatment of acute pancreatitis and also impacts on how ASCVD risk is managed. More work needs to be done to establish the mechanism for the ability of how EPA lowers ASCVD and how to best integrate it with other lipid-lowering therapies. The efficacy and safety of the novel therapies for HTG should be established soon in the ongoing late-stage clinical trials.

COVID-19-Associated dyslipidemia: Implications for mechanism of impaired resolution and novel therapeutic approaches.

The current coronavirus disease 2019 (COVID-19) pandemic presents a global challenge for managing acutely ill patients and complications from viral infection. Systemic inflammation accompanied by a "cytokine storm," hemostasis alterations and severe vasculitis have all been reported to occur with COVID-19, and emerging evidence suggests that dysregulation of lipid transport may contribute to some of these complications. Here, we aim to summarize the current understanding of the potential mechanisms related to COVID-19 dyslipidemia and propose possible adjunctive type therapeutic approaches that modulate lipids and lipoproteins. Specifically, we hypothesize that changes in the quantity and composition of high-density lipoprotein (HDL) that occurs with COVID-19 can significantly decrease the anti-inflammatory and anti-oxidative functions of HDL and could contribute to pulmonary inflammation. Furthermore, we propose that lipoproteins with oxidized phospholipids and fatty acids could lead to virus-associated organ damage via overactivation of innate immune scavenger receptors. Restoring lipoprotein function with ApoA-I raising agents or blocking relevant scavenger receptors with neutralizing antibodies could, therefore, be of value in the treatment of COVID-19. Finally, we discuss the role of omega-3 fatty acids transported by lipoproteins in generating specialized proresolving mediators and how together with anti-inflammatory drugs, they could decrease inflammation and thrombotic complications associated with COVID-19.

[Simultaneous rapid detection of ten stilbenes in serum of mice by UPLC-MS/MS].

Stilbenes is a class of natural polyphenols with 1,2-diphenylethylene as the skeleton structure which have structural and active diversity. However, there are fewer studies on their metabolic process, which limits the in-depth research and development of such components. An UPLC-MS/MS method simultaneously determining contents of ten stilbenes was firstly established in this study and applied to study the ten stilbenes of peony seed coats in the serum of C57 mice.Piceatannol was the internal standard, and methanol was used for protein precipitation, UPLC-MS/MS with negative ion mode was used for analysis, and the method was validated.The serum samples were collected and detected after mice being oral administered with 800 mg·kg~(-1) peony seed coat extracts for 8 weeks. The results showed that suffruticosol A, suffruticosol B, suffruticosol C, trans-ε-viniferin, cis-gnetin H, trans-suffruticosol D and trans-gnetin H were detected in serum samples, and the highest is suffruticosol A. The method is simple and quick with high specificity and sensitivity, and it is suitable for quantitative determination of ten stilbenes in the serum of mice.

Comparison of Omega-3 Eicosapentaenoic Acid Versus Docosahexaenoic Acid-Rich Fish Oil Supplementation on Plasma Lipids and Lipoproteins in Normolipidemic Adults.

BACKGROUND: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have both shared and different cardiovascular effects, and commonly used fish oil supplements have considerably varied EPA/DHA ratios. AIMS: We compared the effects of fish oil supplements with different EPA/DHA ratios on lipoprotein metabolism. METHODS: In a double-blind, randomized cross-over study, normolipidemic adults (n = 30) consumed 12 g/day of EPA-rich (EPA/DHA: 2.3) or DHA-rich (EPA/DHA: 0.3) fish oil for 8-weeks, separated by an 8-week washout period. RESULTS: Both fish oil supplements similarly lowered plasma TG levels and TG-related NMR parameters versus baseline (p < 0.05). There were no changes in plasma cholesterol-related parameters due to either fish oil, although on-treatment levels for LDL particle number were slightly higher for DHA-rich oil compared with EPA-rich oil (p < 0.05). Both fish oil supplements similarly altered HDL subclass profile and proteome, and down regulated HDL proteins related to inflammation, with EPA-rich oil to a greater extent. Furthermore, EPA-rich oil increased apoM abundance versus DHA-rich oil (p < 0.05). CONCLUSIONS: Overall, fish oil supplements with varied EPA/DHA ratios had similar effects on total lipids/lipoproteins, but differences were observed in lipoprotein subfraction composition and distribution, which could impact on the use of EPA versus DHA for improving cardiovascular health.

Supplementation with saury oil, a fish oil high in omega-11 monounsaturated fatty acids, improves plasma lipids in healthy subjects.

BACKGROUND: Fish oil enriched in omega-11 long-chain monounsaturated fatty acids (LCMUFAs; C20:1 and C22:1 isomers combined) have shown lipid-lowering and atheroprotective effects in animal models. OBJECTIVE: To perform a first-in-human trial of LCMUFA-rich saury fish oil supplementation to test its safety and possible effect on plasma lipids. METHODS: A double-blind, randomized, crossover clinical trial was carried out in 30 healthy normolipidemic adults (BMI <25 kg/m2; mean TG, 84 mg/dL). Treatment periods of 8 weeks were separated by an 8-week washout period. Subjects were randomized to receive either 12 g of saury oil (3.5 g of LCMUFA and 3.4 g of omega-3 FAs) or identical capsules with control oil (a mixture of sardine and olive oil; 4.9 g of shorter-chain MUFA oleate and 3 g of omega-3 FAs). RESULTS: Saury oil supplementation was safe and resulted in LDL particle counts 12% lower than control oil (P < .001). Saury oil also had a minor effect on increasing HDL particle size (9.8 nm vs 9.7 nm; P < .05) based on a linear mixed effect model. In contrast, control oil, but not saury oil, increased LDL-C by 7.5% compared with baseline (P < .05). Saury oil had similar effects compared with control oil on lowering plasma TG levels, VLDL, and TG-rich lipoprotein particle counts (by ∼16%, 25%, and 35%, respectively; P < .05), and increasing HDL-C and cholesterol efflux capacity (by ∼6% and 8%, respectively; P < .05) compared with baseline. CONCLUSION: Saury oil supplementation is well tolerated and has beneficial effects on several cardiovascular parameters, such as LDL particle counts, HDL particle size, and plasma TG levels.

Gastrodin Ameliorates Motor Learning Deficits Through Preserving Cerebellar Long-Term Depression Pathways in Diabetic Rats.

Cognitive dysfunction is a very severe consequence of diabetes, but the underlying causes are still unclear. Recently, the cerebellum was reported to play an important role in learning and memory. Since long-term depression (LTD) is a primary cellular mechanism for cerebellar motor learning, we aimed to explore the role of cerebellar LTD pathways in diabetic rats and the therapeutic effect of gastrodin. Diabetes was induced by a single injection of streptozotocin into adult Sprague-Dawley rats. Motor learning ability was assessed by a beam walk test. Pathological changes of the cerebellum were assessed by Hematoxylin-Eosin (HE) and Nissl staining. Cellular apoptosis was assessed by anti-caspase-3 immunostaining. Protein expression levels of LTD pathway-related factors, including GluR2, protein kinase C (PKC), NR2A, and nNOS, in the cerebellar cortex were evaluated by western blotting and double immunofluorescence. The NO concentration was measured. The cellular degeneration and the apoptosis of Purkinje cells were evident in the cerebellum of diabetic rats. Protein expression levels of GluR2 (NC9W: 1.26 ± 0.12; DM9W + S: 0.81 ± 0.07), PKC (NC9W: 1.66 ± 0.10; DM9W + S: 0.58 ± 0.19), NR2A (NC9W: 1.40 ± 0.05; DM9W + S: 0.63 ± 0.06), nNOS (NC9W: 1.26 ± 0.12; DM9W + S: 0.68 ± 0.04), and NO (NC9W: 135.61 ± 31.91; DM9W + S: 64.06 ± 24.01) in the cerebellum were significantly decreased in diabetic rats. Following gastrodin intervention, the outcome of motor learning ability was significantly improved (NC9W: 6.70 ± 3.31; DM9W + S: 20.47 ± 9.43; DM9W + G: 16.04 ± 7.10). In addition, degeneration and apoptosis were ameliorated, and this was coupled with the elevation of the protein expression of the abovementioned biomarkers. Arising from the above, we concluded that gastrodin may contribute to the improvement of motor learning by protecting the LTD pathways in Purkinje cells.