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.

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.

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.

[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.

Expression Changes of NMDA and AMPA Receptor Subunits in the Hippocampus in rats with Diabetes Induced by Streptozotocin Coupled with Memory Impairment.

Cognitive impairment in diabetes (CID) is a severe chronic complication of diabetes mellitus (DM). It has been hypothesized that diabetes can lead to cognitive dysfunction due to expression changes of excitatory neurotransmission mediated by N-methyl-D-aspartate receptors (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR); however, the pathogenesis involved in this has not been fully understood, especially at early phase of DM. Here, we sought to determine the cognitive changes and aim to correlate this with the expression changes of NMDAR and AMPAR of glutamate signaling pathways in the rat hippocampus from early phase of DM and in the course of the disease progression. By Western blot analysis and immunofluorescence labeling, the hippocampus in diabetic rats showed a significant increase in protein expression NMDAR subunits NR1, NR2A and NR2B and AMPAR subunit GluR1. Along with this, behavioral test by Morris water maze showed a significant decline in their performance when compared with the control rats. It is suggested that NR1, NR2A, NR2B and GluR1are involved in learning and memory and that their expression alterations maybe correlated with the occurrence and development of CID in diabetic rats induced by streptozotocin.

Nemo-like kinase as a negative regulator of nuclear receptor Nurr1 gene transcription in prostate cancer.

BACKGROUND: Nurr1, a member of the orphan receptor family, plays an important role in several types of cancer. Our previous work demonstrated that increased expression of Nurr1 plays a significant role in the initiation and progression of prostate cancer (PCa), though the mechanisms for regulation of Nurr1 expression remain unknown. In this study, we investigated the hypothesis that Nemo-like kinase (NLK) is a key regulator of Nurr1 expression in PCa. METHODS: Immunohistochemistry and Western blot analysis were used to evaluate levels of NLK and Nurr1 in prostatic tissues and cell lines. The effects of overexpression or knockdown of Nurr1 were evaluated in PCa cells through use of PCR, Western blots and promoter reporter assays. The role of Nurr1 promoter cis element was studied by creation of two mutant Nurr1 promoter luciferase constructs, one with a mutated NF-κB binding site and one with a mutated CREB binding site. In addition, three specific inhibitors were used to investigate the roles of these proteins in transcriptional activation of Nurr1, including BAY 11-7082 (NF-κB inhibitor), KG-501 (CREB inhibitor) and ICG-001 (CREB binding protein, CBP, inhibitor). The function of CBP in NLK-mediated regulation of Nurr1 expression was investigated using immunofluorescence, co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation assays (ChIPs). RESULTS: NLK expression was inversely correlated with Nurr1 expression in prostate cancer tissues and cell lines. Overexpression of NLK suppressed Nurr1 promoter activity, leading to downregulation of Nurr1 expression. In contrast, knockdown of NLK demonstrated opposite results, leading to upregulation of Nurr1. When compared with the wild-type Nurr1 promoter, mutation of NF-κB- and CREB-binding sites of the Nurr1 promoter region significantly reduced the upregulation of Nurr1 induced by knockdown of NLK in LNCaP cells; treatment with inhibitors of CREB, CBP and NF-κB led to similar results. We also found that NLK directly interacts with CBP, that knockdown of NLK significantly increases the recruitment of CBP to both NF-κB- and CREB-binding sites, and that regulation of NLK on Nurr1 expression is abrogated by knockdown of CBP. CONCLUSIONS: Our results suggest that NLK inhibits transcriptional activation of Nurr1 gene by impeding CBP's role as a co-activator of NF-κB and CREB in prostate cancer.

Dietary marine-derived long-chain monounsaturated fatty acids and cardiovascular disease risk: a mini review.

Regular fish/fish oil consumption is widely recommended for protection against cardiovascular diseases (CVD). Fish and other marine life are rich sources of the cardioprotective long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) eicosapentaenoic acid (C20:5 n-3; EPA) and docosahexaenoic acid (C22:6 n-3; DHA). The lipid content and fatty acid profile of fish, however, vary greatly among different fish species. In addition to n-3 PUFA, certain fish, such as saury, pollock, and herring, also contain high levels of long-chain monounsaturated fatty acids (LCMUFA), with aliphatic tails longer than 18 C atoms (i.e., C20:1 and C22:1 isomers). Compared with well-studied n-3 PUFA, limited information, however, is available on the health benefits of marine-derived LCMUFA, particularly in regard to CVD. Our objective in this review is to summarize the current knowledge and provide perspective on the potential therapeutic value of dietary LCMUFA-rich marine oil for improving CVD risk factors. We will also review the possible mechanisms of LCMUFA action on target tissues. Finally, we describe the epidemiologic data and small-scaled clinical studies that have been done on marine oils enriched in LCMUFA. Although there are still many unanswered questions about LCMUFA, this appears to be promising new area of research that may lead to new insights into the health benefits of a different component of fish oils besides n-3 PUFA.

Long-term dietary supplementation with saury oil attenuates metabolic abnormalities in mice fed a high-fat diet: combined beneficial effect of omega-3 fatty acids and long-chain monounsaturated fatty acids.

BACKGROUND: Pacific saury is a common dietary component in East Asia. Saury oil contains considerable levels of n-3 unsaturated fatty acids (PUFA) and long-chain monounsaturated fatty acids (LCMUFA) with aliphatic tails longer than 18 carbons. In our previous study, consumption of saury oil for 4 to 6 wk improved insulin sensitivity and the plasma lipid profile in mice. However, the long-term effects of saury oil on metabolic syndrome (MetS) risk factors remain to be demonstrated. In the current study, we examined the long-term effects of saury oil on mice fed a high-fat diet, and compared the effect of n-3 PUFA EPA and LCMUFA on MetS risk factor in diet-induced obese mice. METHODS AND RESULTS: In Experiment 1, male C57BL/6 J mice were fed either a 32% lard diet (control) or a diet containing 22% lard plus 10% saury oil (saury oil group) for 18 weeks. Although no differences were found in body weight and energy expenditure between the control and saury oil groups, the saury oil diet decreased plasma insulin, non-HDL cholesterol, hepatic steatosis, and adipocyte size, and altered levels of mRNA transcribed from genes involved in insulin signaling and inflammation in adipose tissue. Organ and plasma fatty acid profile analysis revealed that consumption of saury oil increased n-3 PUFA and LCMUFA (especially n-11 LCMUFA) levels in multiple organs, and decreased the fatty acid desaturation index (C16:1/C16:0; C18:1/C18:0) in liver and adipose tissue. In Experiment 2, male C57BL/6 J mice were fed a 32% lard diet (control), a diet containing 28% lard plus 4% EPA (EPA group), or a diet containing 20% lard plus 12% LCMUFA concentrate (LCMUFA group) for 8 weeks. EPA or LCMUFA intake increased organ levels of EPA and LCMUFA, respectively. Consumption of EPA reduced plasma lipid levels and hepatic lipid deposition, and decreased the fatty acid desaturation index in liver and adipose tissue. Consumption of LCMUFA decreased plasma non-HDL cholesterol, improved hyperinsulinemia, and decreased the fatty acid desaturation index in adipose tissue. EPA accumulated mainly in liver, and LCMUFA (especially n-11 LCMUFA) accumulated mainly in white adipose tissue, suggesting their possible individual biological effects for improving MetS. CONCLUSION: Our results suggest that saury oil-mediated improvement of metabolic syndrome in diet-induced obese mice may possibly be due to a combined effect of n-3 PUFA and LCMUFA.

[Effect of Ju-Pi-Tang on Cisplatin-induced Emetic Model in Minks].

OBJECTIVE: To study the antiemetic effect of Ju-Pi-Tang from Jin Kui Yao Lue on cisplatin-induced emetic model in minks, and to observe the immunoexpression of peripheral and central c-fos and substance P. METHODS: The minks were randomly divided into blank control group, Ju-Pi-Tang blank control group, model group, ondansetron group, aprepitant group, Ju-Pi-Tang (in high-, mid-, and low-dose) groups. Every group was administered with the antiemetic agent or distilled water on 24 h before cisplatin injection. The antiemetic effect of drugs was investigated in the emetic model of minks induced by cisplatin in 72 h observation. Immunohistochemistry was used to compare the differences of c-fos and substance P expression in the area postrema of brain and distal ileum tissues. RESULTS: During observation period,compared with model group,the frequency cisplatin induced retching and vomiting was significantly reduced by Ju-Pi-Tang in high- and mid-dose groups, during the 0-24 h acute period, the number of retching of Ju-Pi-Tang in high-dose group was decreased more than aprepitant group, during the 24-72 h delayed period, the number of both retching and vomiting was decreased more than ondansetron group, after 72 h of cisplatin administration, compared with model group, the grey levels of c-fos and substance P expression in distal ileum and brain tissues of Ju-Pi-Tang groups were higher significantly. CONCLUSION: Ju-Pi-Tang has a good effect against cisplatin-induced emesis in minks.

[Simultaneous determination of six Salvia miltiorrhiza gradients in rat plasma and brain by LC-MS/MS].

To develop a LC-MS/MS method for the determination of protocatechuic acid, protocatechuic aldehyde, salvianolic acid A, salvianolic acid B, cryptotanshinone and tanshinone II(A) in rat plasma and brain. The plasma and brain samples were precipitated with ethyl acetate, then were separated on an Agilent eclipse plus-C18 column (2.1 mm x 50 mm, 3.5 microm) using acetonitrile (consisting of 0.1% formic acid) and water (consisting of 0.1% formic acid) as mobile phase in gradient elution mode. The mass spectrometer was operated under both positive and negative ion mode with the ESI source, and the detection was performed by MRM. The transition of 154.3/153.1 m/z for protocatechuic acid, 137.3/108 m/z for protocatechuic aldehyde, 493.0/295.2 m/z for Salvianolic acid A, 718.0/520.0 m/z for salvianolic acid B, 321.4/152.3 m/z for chloramphenicol, 297.4/254.3 m/z for cryptotanshinone, 295.5/249.3 m/z for tanshinone II(A) and 285.2/154.0 m/z for Diazepam. The calibration curves in the range of 0.625-1 000 microg x L(-1) for protocatechuic acid and protocatechuic aldehyde, 1.25-1 000 microg x L(-1) for salvianolic acid A, 2.5-1 000 microg x L(-1) for salvianolic acid B, 0.15-1 000 microg x L(-1) for cryptotanshinone, 0.625-1 000 microg x L(-1) for tanshinone II(A) are with good linearityin rat plasma and brain. The analysis method is sensitive, simple, and suitable enough to be applied in the pharmacokinetic study of the 6 main components. Animal testing gives the lgBB of the drugs and further studies of the 6 components cross the blood-brain barrier can be carried out.

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.

Oral administration of omega-7 palmitoleic acid induces satiety and the release of appetite-related hormones in male rats.

We have analyzed the effect of palmitoleic acid on short-term food intake in male rats. Administration of omega-7 palmitoleic acid by oral gavage significantly decreased food intake compared to palmitic acid, omega-9 oleic acid, or a vehicle control. Palmitoleic acid exhibited a dose-dependent effect in this context and did not cause general malaise. A triglyceride form of palmitoleate also decreased food intake, whereas olive oil, which is rich in oleic acid, did not. Palmitoleic acid accumulated within the small intestine in a dose-dependent fashion and elevated levels of the satiety hormone cholecystokinin (CCK). Both protein and mRNA levels of CCK were affected in this context. The suppression of food intake by palmitoleic acid was attenuated by intravenous injection of devazepide, a selective peripheral CCK receptor antagonist. Palmitoleic acid did not alter the expression of peroxisome proliferator-activated receptor alpha (PPARα) target genes, and a PPARα antagonist did not affect palmitoleic acid-induced satiety. This suggests that the PPARα pathway might not be involved in suppressing food intake in response to palmitoleic acid. We have shown that orally administered palmitoleic acid induced satiety, enhanced the release of satiety hormones in rats.

Comparison between conidia and blastospores of Esteya vermicola, an endoparasitic fungus of the pinewood nematode, Bursaphelenchus xylophilus.

Esteya vermicola, an endoparasitic fungus of Bursaphelenchus xylophilus, the pinewood nematode (PWN), exhibits great potential as a biological control agent against this nematode. E. vermicola produces blastospores in liquid media and aerial conidia on solid media. The agent was mass-produced using two kinds of culture media: S (50 % wheat bran and 50 % pine wood powder), L (0.5 g wheat bran and 0.5 g pinewood powder in 200 ml of potato dextrose broth), and two controls: SC (potato dextrose agar), LC (potato dextrose broth). Yields, multiple stress tolerance, storage life, new generation conidial number, and PWN mortality rates of the spores were measured in each of these four media and compared. The spore yields, new generation conidial number, and nematode mortality rates of blastospores were higher than those of conidia. Nevertheless, the conidia had a higher germination rate than the blastospores during the storage process and multiple stress treatments. Considering the number of spores surviving from the process of the storage and multiple stress treatments per unit of mass media, the blastospores from L survived most. Comprehensive analysis indicates that the L culture medium is the most optimal medium for mass production relatively.

[Advance in studies on chemical constitutions, pharmacological mechanism and pharmacokinetic profile of dalbergiae odoriferae lignum].

Dalbergiae Odoriferae Lignum is a traditional Chinese medicine (TCM) commonly used for promoting blood circulation, relieving pain and removing blood stasis. Volatile oil and flavonoid compounds are two main chemical constituents of Dalbergiae Odoriferae Lignum. Modern pharmacological studies show that Dalbergiae Odoriferae Lignum has many effects, such as relaxing blood, increasing blood flow of coronary, anti-oxidation, anti-inflammation and antitumor. Dalbergiae Odoriferae Lignum, as a characteristic TCM with the potential of further development, is generally compatible with other TCMs to treat cardio-cerebral vascular diseases. This article summarizes studies on chemical composition, pharmacological action, pharmacokinetic procfile in vivo and TCM compatibility in recent years, in order to provide references for further studies.

[Pharmacokinetics study on Danshensu in rats by brain microdialysis and automated blood technique].

To research the pharmacokinetic of Danshensu in brain via microdialysis method and automated blood technique. A microdialysis probe was inserted into the left lateral ventricle, and then dialysate samples and blood samples were continuously collected after iv Danshensu. LC-MS/MS was used to determinate for Danshensu in the dialysate samples. The in vivo recovery was used for the calibration of probe. WinNonlin was used for analyzing all pharmacokinetic data. Pharmacokinetic parameters of DSS in blood and in brain showed that Ke, t1/2,, AUC0-t, MRT were 0.04, 0.018 min(-1), 16.64, 58.76 min, 812.59, 51.19 min x mg x L(-1), 15.28, 79.97 min, respectively. The results were indicated that the study was successfully established LC-MS/MS detection method for Danshensu. Microdialysis combined with automated blood technique could better reflect the dynamic characteristics of Danshensu in the rat brain, and it provides a new perspective for pharmacokinetic study.