Sir2 (silent information regulator-2), an NAD⁺-dependent histone deacetylase, is highly conserved in organisms ranging from archaea to humans. Yeast Sir2 is responsible for silencing at repeated DNA sequences in mating-type loci, telomeres and rDNA, and plays critical roles in DNA repair, stress resistance and longevity.
The phenomenon of human aging is known to be a critical cardiovascular risk factor. Senescence of endothelial cells has been proposed to be involved in vascular dysfunction and atherogenesis. Recent studies have demonstrated that mammalian Sirt1 NAD⁺-dependent protein deacetylase, the closest homologue of Sir2, regulates vascular angiogenesis, homeostasis and senescence. This review focuses on SIRT1 as a potential therapeutic target against atherosclerosis.

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Japanese native chickens (JNCs) comprise approximately 50 breeds, making Japan a diversity hotspot for native chicken breeds. JNCs were established through the repeated introduction of chickens from foreign countries. Jidori, which is the generic name of JNC breeds whose ancestral morphology resembles that of their wild progenitor (red junglefowls), is generally thought to have propagated from north East Asia (Korea and north China) to ancient Japan. However, mitochondrial haplogroup D, which is abundant in Island Southeast Asia (ISEA) as well as the Pacific but relatively rare in other regions, can be observed in some Jidori breeds (e.g., Tosa-Jidori, Tokuji-Jidori) with high frequency, leading to speculation that chickens from ISEA or the Pacific also contributed genetically to JNCs. To test this hypothesis, we sequenced the mitochondrial genomes of Jidori breeds and conducted phylogeographic analysis. Our results indicate that the JNC Haplogroup D belongs to Sub-haplogroup D2, which is currently only observed in Xinjiang, northwest China, and not to Sub-haplogroup D1, which is widely distributed in the ISEA-Pacific region. The other mitochondrial haplogroups of Jidori examined in this study also showed affinity to those of chickens native to north East Asia. Therefore, our findings support the north East Asian origin hypothesis for Jidori.

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Despite the recent progress in the diagnosis and treatment of cardiovascular diseases, these are still a major source of morbidity and mortality worldwide. For this reason, a large research effort was directed to the identification of the underlying pathophysiological aspects of cardiovascular diseases. Nevertheless, many mechanisms still need to be more deeply investigated, limiting the development of efficient diagnostic and therapeutic strategies for a relevant number of patients. Recently, microRNAs (miRs) emerged as powerful regulators of biological processes, offering a further opportunity to better understand the biological mechanisms responsible for the development of cardiovascular diseases, including cellular function and cell-to-cell communication. At the same time, the recent demonstration that cell-derived circulating miRs can be measured in the blood opens up their use as powerful biomarkers. The present review summarizes the most relevant experimental evidences on the involvement of miRs in cardiovascular diseases, including vascular remodeling, coronary artery disease, heart failure and ischemic stroke, thus highlighting potential targets for novel therapeutic strategies.  (Circ J 2014; 78: 567–575)

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Resveratrol (RSV), 3,5,4'-trihydroxy-trans-stilbene, is known to have many beneficial physiological activities. We have synthesized several stilbene anlogues and have reported that the hydroxyl group in the 4' position of RSV exhibited strong radical scavenging action. Using stilbene analogs, we investigated the structure of RSV to explain its protective effect against obesity and type 2 diabetes. All six analogs used in this study inhibited the differentiation of 3T3-L1 adipocytes. 3-Hydroxy-trans stilbene (3(OH)ST), and 3,4'-dihydroxy-trans stilbene (3,4'(OH)₂ST) increased glucose uptake and induced adenosine monophosphate kinase (AMPK) phosphorylation in C2C12 myotubes independently of insulin. An in vivo study using mice fed high-fat diets indicated that 3(OH)ST was more effective than RSV in improving insulin resistance. In conclusion, RSV and its derivatives, particularly 3(OH)ST, inhibited adipocyte differentiation and enhanced glucose uptake in the myotubes, resulting in a reduction of obesity and an improvement in glucose tolerance in vivo.

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It is well established that vesicular nucleotide transporter (VNUT) is responsible for vesicular storage of nucleotides such as ATP, and that VNUT-expressing cells can secrete nucleotides upon exocytosis, playing an important role in purinergic chemical transmission. In the present study, we show that VNUT is expressed in intestinal L cells. Immunohistochemical evidence indicated that VNUT is present in glucagon-like peptide 1 (GLP-1) containing cells in rat intestine. VNUT immunoreactivity is not co-localized with GLP-1, a marker for secretory granules, and synaptophysin, a marker for synaptic-like microvesicles (SLMVs). Essentially the same results were obtained for GLUTag clonal L cells. Sucrose density gradient analysis confirmed that VNUT is present the light fraction, unlike secretory granules. These results demonstrate that intestinal L cells express VNUT in either the unidentified organelles at light density other than secretory granules and SLMVs or a subpopulation of SLMVs, and suggest that L cells are purinergic in nature and secrete nucleotides independent of GLP-1 secretion.

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Abnormal elevation of low-density lipoprotein (LDL) and triglyceride-rich lipoproteins in plasma as well as dysfunction of anti-atherogenic high-density lipoprotein (HDL) have both been recognized as essential components of the pathogenesis of atherosclerosis and are classified as dyslipidemia. This review describes the arc of development of antisense oligonucleotides for the treatment of dyslipidemia. Chemically-armed antisense candidates can act on various kinds of transcripts, including mRNA and miRNA, via several different endogenous antisense mechanisms, and have exhibited potent systemic anti-dyslipidemic effects. Here, we present specific cutting-edge technologies have recently been brought into antisense strategies, and describe how they have improved the potency of antisense drugs in regard to pharmacokinetics and pharmacodynamics. In addition, we discuss perspectives for the use of armed antisense oligonucleotides as new clinical options for dyslipidemia, in the light of outcomes of recent clinical trials and safety concerns indicated by several clinical and preclinical studies.

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　This study examines the effects of a low-protein diet on cholesterol metabolism in rats under constant darkness. The experiment was conducted in two-way layout methods with two factors: lighting conditions and dietary protein levels. Each factor has two levels: lighting condition has normal lighting (7:00-19:00; light period, 19:00-7:00; dark period, N) and constant darkens (D); dietary protein levels has 5% casein (5%) and 20% casein (20%). Forty-eight Fisher strain 4-week-old female rats were divided into four groups based on the two factors and levels. At the end of the fourth week, three rats in each group were euthanized at 14:00, 20:00, 2:00, and 8:00. The effects of lighting condition and dietary protein level on the serum total and hepatic cholesterol concentrations were observed. The D-condition serum concentration was higher than that of the N-condition (p＜0.01) and that of the 5%-diet was lower than that of the 20%-diet (p＜0.01). Conversely, the D-condition hepatic concentration was lower than that of the N-condition (p＜0.05) and that of the 5%-diet was higher than that of the 20%-diet (p＜0.01). The effects of both factors on ApoC3, an apolipoprotein of VLDL, were observed. The ApoC3 mRNA expression of the D-condition was higher than that of the N-condition (p＜0.01), and that of the 5%-diet was lower than that of the 20%-diet (p＜0.01). We also observed lighting condition on mRNA expressions of Lrp1 (a receptor of lipoprotein) at 2:00 and Hmgcr (a rate-limiting enzyme of cholesterol synthesis) at 20:00. The mRNA expressions of both genes in the D-condition were lower than in the N-condition (p＜0.05). There were no significant differences between lighting conditions and dietary protein levels. Therefore, both factors were acting independently, and the decrease in the serum concentration by low-protein diet was related to ApoC3 and the increase by constant darkness was related to ApoC3, Lrp1, and Hmgcr.

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Glucagon-like peptide-1 (GLP-1), an incretin hormone, is secreted from L cells located in the intestinal epithelium. It is known that intestinal oxygen tension is decreased postprandially. In addition, we found that the expression of hypoxia-inducible factor-1α (HIF-1α), which accumulates in cells under hypoxic conditions, was significantly increased in the colons of mice with food intake, indicating that the oxygen concentration is likely reduced in the colon after eating. Therefore, we hypothesized that GLP-1 secretion is affected by oxygen tension. We found that forskolin-stimulated GLP-1 secretion from GLUTag cells, a model of intestinal L cells, is suppressed in hypoxia (1% O₂). Forskolin-stimulated elevations of preproglucagon (ppGCG) and proprotein convertase 1/3 (PC1/3) mRNA expression were decreased under hypoxic conditions. The finding that H89, a protein kinase A (PKA) inhibitor, inhibited the forskolin-stimulated increase of ppGCG and PC1/3 indicated that the cAMP-PKA pathway is involved in the hypoxia-induced suppression of the genes. Hypoxia decreased hexokinase 2 mRNA and protein expression and increased lactate dehydrogenase A mRNA and protein expression. Concomitantly, lactate production was increased and ATP production was decreased. Together, the results indicate that hypoxia decreases glucose utilization for ATP production, which probably causes a decrease in cAMP production and in subsequent GLP-1 production. Our findings suggest that the postprandial decrease in oxygen tension in the intestine attenuates GLP-1 secretion.

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　主竜類（ワニ類，翼竜類，そして鳥類を含む恐竜類など）は，非常に多様で成功した陸上脊椎動物である．絶滅種（例，非鳥類型恐竜類）及び現生種（ワニ類及び鳥類）の営巣方法や営巣行動を理解することは，主竜類の進化や多様性を検討する上で重要である．しかしながら，恐竜類の営巣方法や営巣行動は，多くの場合，化石記録から直接観察できないため，かれらの営巣様式（巣の構造，抱卵行動，孵化日数など）は，卵・巣・胚化石から得られる特徴（クラッチサイズ，卵重，卵殻間隙率，胚の形態的特徴など）を用いて推定・復元される．非鳥類型恐竜類の巣や営巣行動は多様だったと考えられ，恐竜類を含め主竜類におけるこれらの形質の進化が議論できる．

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Obesity-related renal diseases have been a worldwide issue. Effective strategy that prevents high fat-diet induced renal damage is of great significance. Resveratrol, a natural plant polyphenol, is famous for its antioxidant activity, cardioprotective effects and anticancer properties. However whether resveratrol can play a role in the treatment of renal diseases is unknown. In this study, we added resveratrol in normal glucose or high glucose medium and provide evidences that resveratrol protects against high-glucose triggered oxidative stress and cell senescence. Moreover, mice were fed with standard diet, standard diet plus resveratrol, high-fat diet or high-fat diet plus resveratrol for 3 months, and results show that resveratrol treatment prevents high-fat diet induced renal pathological damage by activating SIRT1, a key member in the mammalian sirtuin family that response to calorie restriction life-extension method. This research confirms the potential role of resveratrol in the treatment of renal diseases and may provide an effective and convenient method to mimic the beneficial effects of calorie restriction.

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