In the present study, we identified several food-derived collagen peptides in human blood after oral ingestion of some gelatin hydrolysates. Healthy human volunteers ingested the gelatin hydrolysates (9.4-23 g) from porcine skin, chicken feet, and cartilage after 12 h of fasting. Negligible amounts of the peptide form of hydroxyproline (Hyp) were observed in human blood before the ingestion. After the oral ingestion, the peptide form of Hyp significantly increased and reached a maximum level (20-60 nmol/mL of plasma) after 1-2 h and then decreased to half of the maximum level at 4 h after the ingestion. Major constituents of food-derived collagen peptides in human serum and plasma were identified as Pro-Hyp. In addition, small but significant amounts of Ala-Hyp, Ala-Hyp-Gly, Pro-Hyp-Gly, Leu-Hyp, Ile-Hyp, and Phe-Hyp were contained.

Homeostasis of brassinosteroids (BRs) is essential for normal growth and development in higher plants. We examined responsiveness of 11 BR metabolic gene expressions to the decrease or increase of endogenous BR contents in Arabidopsis (Arabidopsis thaliana) to expand our knowledge of molecular mechanisms underlying BR homeostasis. Five BR-specific biosynthesis genes (DET2, DWF4, CPD, BR6ox1, and ROT3) and two sterol biosynthesis genes (FK and DWF5) were upregulated in BR-depleted wild-type plants grown under brassinazole, a BR biosynthesis inhibitor. On the other hand, in BRexcessive wild-type plants that were fed with brassinolide, four BR-specific synthesis genes (DWF4, CPD, BR6ox1, and ROT3) and a sterol synthesis gene (DWF7) were down-regulated and a BR inactivation gene (BAS1) was up-regulated. However, their response to fluctuation of BR levels was highly reduced (DWF4) or nullified (the other eight genes) in a bri1 mutant. Taken together, our results imply that BR homeostasis is maintained through feedback expressions of multiple genes, each of which is involved not only in BR-specific biosynthesis and inactivation, but also in sterol biosynthesis. Our results also indicate that their feedback expressions are under the control of a BRI1-mediated signaling pathway. Moreover, a weak response in the mutant suggests that DWF4 alone is likely to be regulated in other way(s) in addition to BRI1 mediation.

Abstract-The klotho gene, originally identified by insertional mutagenesis in mice, suppresses the expression of multiple aging-associated phenotypes. This gene is predominantly expressed in the kidney. Recent studies have shown that expression of renal klotho gene is regulated in animal models of metabolic diseases and in humans with chronic renal failure. However, little is known about the mechanisms and the physiological relevance of the regulation of the expression of the klotho gene in the kidney in some diseased conditions. In the present study, we first investigated the role of angiotensin II in the regulation of renal klotho gene expression. Long-term infusion of angiotensin II downregulated renal klotho gene expression at both the mRNA and protein levels. This angiotensin II-induced renal klotho downregulation was an angiotensin type 1 receptor-dependent but pressor-independent event. Adenovirus harboring mouse klotho gene (ad-klotho, 3.3ϫ10 10 plaque forming units) was also intravenously administered immediately before starting angiotensin II infusion in some rats. This resulted in a robust induction of Klotho protein in the liver at day 4, which was still detectable 14 days after the gene transfer. T he klotho gene, identified by insertional mutagenesis in mice, is a suppressor of the expression of multiple aging phenotypes similar to age-related diseases in humans, such as arteriosclerosis, osteoporosis, infertility, pulmonary emphysema, and short lifespan. 1 Interestingly, expression of klotho mRNA in the kidney can be only faintly detected in the prenatal rat, and it is markedly augmented after 4 days of age. 2 Although the klotho gene has a role in phenotypic alterations in various organs, expression of klotho mRNA is predominantly observed in the kidney, 1 suggesting that the Klotho protein or its metabolites may function as humoral factors. Recent studies have shown that expression of renal klotho gene is regulated in animals 2 and in humans 3 in some diseased conditions. At present, however, the mechanism regulating klotho gene expression is poorly understood.In the present study, we have investigated the role of angiotensin (Ang) II in the regulation of renal klotho gene expression. In addition, to clarify the possible physiological role of the klotho gene in the Ang II-infused rats, exogenous klotho gene was delivered into Ang II-infused rats, and functional and histological changes in the kidney were analyzed. Methods Animal ModelsThe experiments were performed in accordance with the guidelines and practices established by the Animal Center for Biomedical Research, University of Tokyo, Faculty of Medicine. The rat Ang II hypertension model was induced in male Sprague-Dawley rats (Nippon Bio-Supply Center, Tokyo, Japan) by the continuous infusion of [Val 5 ]-Ang II (Sigma) at a dose of 0.7 mg/kg per day via an osmotic minipump (Alza) as described previously. 4 In some experiments, the selective angiotensin type 1 receptor antagonist losartan (25 mg/kg per day; a gift from Merck, Rahway, NJ) ...

A baseline signature of a low ANC, high ALC, and high AEC was associated with a better outcome of nivolumab treatment, with the number of favorable factors identifying subgroups of patients differing in survival and response rate.

Metastasis to the regional lymph nodes through the lymphatic vessels is a common step in the progression of cancer and an important prognostic factor in many types of cancer. Recent evidence suggests that VEGF-C promotes lymphangiogenesis, and that tumor lymphangiogenesis in turn promotes lymphatic metastasis. We have studied the role of LVD in breast cancer, and examined whether LVD is associated with lymph node metastasis, VEGF-C expression, or prognosis. In addition, we examined whether VEGF-C mRNA transcript levels were associated with lymph node metastasis and LVD. We began by investigating the lymphatics in primary human breast carcinoma with long-term follow-up (113 cases of invasive ductal and other breast cancers) by quantitative immunohistochemical staining for podoplanin. We then analyzed the relationship between LVD and lymph node status as well as VEGF-C immunoreactivity and other established clinicopathological parameters. The relationship between LVD and prognosis was also studied. VEGF-C mRNA transcript levels were examined by quantitative real-time RT-PCR, in 55 invasive ductal breast carcinomas. This was followed by an analysis of the relationship between VEGF-C mRNA transcript levels and lymph node metastasis as well as LVD. Mean LVD of 'hot spots' was 10.2 +/- 7.4/each case. LVD was significantly correlated with lymph node metastasis (p < 0.0001), VEGF-C immunoreactivity (p = 0.0084), and podoplanin positive lymphatic invasion (p < 0.0001). Survival curves determined by the Kaplan-Meier method and univariate analysis demonstrated that high LVD was associated with both worse disease free survival (p = 0.0033) and overall survival (p = 0.0391). VEGF-C mRNA transcript levels were also correlated with lymph node metastasis (p = 0.0074) and LVD (p = 0.0409). Increased LVD was correlated with lymph node metastasis and VEGF-C expression. High LVD may be a significant unfavorable prognostic factor for long-term survival in breast cancer.

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Photoelectrochemical reduction of carbon dioxide (CO2) on p-type silicon (p-Si) electrodes modified with small metal (Cu, Ag, or Au) particles has been studied. The electrodes in CO2-saturated aqueous electrolyte under illumination produce methane, ethylene, carbon monoxide, etc., similar to the metal (Cu, Ag, or Au) electrodes, but at ca. 0.5 V more positive potentials than the corresponding metal electrodes, contrary to continuous-metal-coated p-Si electrodes. The results clearly show that the metal-particle-coated p-Si electrodes not only have high catalytic activity for electrode reactions but also generate high photovoltages and thus work as an ideal type semiconductor electrode. It is discussed that the CO2 photoreduction proceeds with an upward shift of the surface band energies of p-Si in order to get energy level matching between the semiconductor and solution reactants, though hydrogen photoevolution occurs without such an upward shift. It is also discussed that the control of surface structure on a nanometer-sized level, as well as on an atomic scale, is important for getting higher efficiencies.

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