Explore the vast range of titles available.

There is some biological plausibility that exogenous melatonin plays a role in preventing liver carcinogenesis. There has been little research on the association between melatonin intake in a normal diet and health outcomes. We evaluated the association between dietary melatonin intake and the incidence of liver cancer in a population‐based prospective study in Japan. This study included 30,824 residents of Takayama city who were 35 years of age or older in 1992 and had participated in the Takayama study, Japan. Dietary intake was assessed using a validated food frequency questionnaire at the baseline. Melatonin content in foods was measured by liquid chromatography–tandem mass spectrometry. Cancer incidence was confirmed through regional population‐based cancer registries in Gifu. Liver cancer was defined as code C22 according to the International Classification of Diseases and Related Health Problems, 10th Revision. Hazard ratios for liver cancer were estimated for the tertile groups of melatonin intake using a Cox proportional hazards model. During the mean follow‐up period of 13.6 years, 189 individuals developed liver cancer. Compared with subjects in the lowest tertile of melatonin intake, those in the middle and highest tertiles had decreased risks of liver cancer, with a significant linear trend after multivariate adjustments (hazard ratios: 0.64 and 0.65, respectively, trend p  = 0.023). There was no significant interaction by sex (interaction p  = 0.54). This initial finding, which needs to be confirmed by further studies, suggests that consuming melatonin‐containing foods might play a role in the prevention of liver cancer.

Differentiation of osteoclasts (OCs) from hematopoietic cells requires cellular interaction with osteoblasts (OBs). Due to the difficulty of live-imaging in the bone, however, the cellular and molecular mechanisms underlying intercellular communication involved in OC differentiation are still elusive. Here, we develop a fracture healing model using the scale of trap:GFP ; osterix:mCherry transgenic zebrafish to visualize the interaction between OCs and OBs. Transplantation assays followed by flow cytometric analysis reveal that most trap:GFP high OCs in the fractured scale are detected in the osterix:mCherry + fraction because of uptake of OB-derived extracellular vesicles (EVs). In vivo live-imaging shows that immature OCs actively interact with osterix:mCherry + OBs and engulf EVs prior to convergence at the fracture site. In vitro cell culture assays show that OB-derived EVs promote OC differentiation via Rankl signaling. Collectively, these data suggest that EV-mediated intercellular communication with OBs plays an important role in the differentiation of OCs in bone tissue. Kobayashi-Sun et al. characterise the healing of fractured bone in the transgenic zebrafish scale by transplantation assays and live imaging, revealing that immature osteoclasts engulf osteoblast-derived extracellular vesicles (EVs) under fracture stress, leading to osteoclast differentiation. This study provides insights into the role of EVs in osteoclastogenesis.

The circadian clock generates behavioral rhythms to maximize an organism’s physiological efficiency. Light induces the formation of these rhythms by synchronizing cellular clocks. In zebrafish, the circadian clock components Period2 (zPER2) and Cryptochrome1a (zCRY1a) are light-inducible, however their physiological functions are unclear. Here, we investigated the roles of zPER2 and zCRY1a in regulating locomotor activity and behavioral rhythms. zPer2 / zCry1a double knockout (DKO) zebrafish displayed defects in total locomotor activity and in forming behavioral rhythms when briefly exposed to light for 3-h. Exposing DKO zebrafish to 12-h light improved behavioral rhythm formation, but not total activity. Our data suggest that the light-inducible circadian clock regulator zCRY2a supports rhythmicity in DKO animals exposed to 12-h light. Single cell imaging analysis revealed that zPER2, zCRY1a, and zCRY2a function in synchronizing cellular clocks. Furthermore, microarray analysis of DKO zebrafish showed aberrant expression of genes involved regulating cellular metabolism, including ATP production. Overall, our results suggest that zPER2, zCRY1a and zCRY2a help to synchronize cellular clocks in a light-dependent manner, thus contributing to behavioral rhythm formation in zebrafish. Further, zPER2 and zCRY1a regulate total physical activity, likely via regulating cellular energy metabolism. Therefore, these circadian clock components regulate the rhythmicity and amount of locomotor behavior.

The high plasma glucose induced in glucose metabolism disorders leads to the non‐enzymatic glucose‐dependent modification (glycation) of type 1 collagen, which is an essential component of bone tissue. The glycation of proteins induces the formation of advanced glycation end‐products, such as carboxymethyl arginine, which is preferentially generated in glycated collagen. However, the effect of advanced glycation end‐product formation on the characteristics of type 1 collagen remains unclear due to the lack of suitable in vitro experimental systems analyzing type 1 collagen. Here, we show that the glycation of type 1 collagen can be analyzed in vitro using a goldfish‐scale bone model. Our study using these scales provides evidence that the advanced glycation end‐product formation in type 1 collagen induced by glyoxal, the carboxymethyl arginine inducer, facilitates the crosslinking of type 1 collagen, decreasing both its strength and flexibility. Here we show that the glycation of type 1 collagen can be analyzed in vitro using a goldfish‐scale bone model. Our study using these scales provides evidence that glycation of type I collagen alpha chains facilitates the crosslinking of type I collagen, decreasing both its strength and flexibility.

In vertebrate females, plasma calcium concentrations decrease after the reproductive period to prevent calcium from leaking from the body. Goldfish scales store calcium internally, which is released into the blood by osteoclast resorption. Previously, we found that melatonin increases calcitonin (CT), an osteoclast inhibitor, through melatonin receptors in goldfish scales, and inhibits osteoclast activity. However, the physiological function of the melatonin-dependent suppression of osteoclast activity is unclear. In this study, we found that plasma calcium levels increased during the reproductive stage in female goldfish and decreased during the post-reproductive stage. Histological and mRNA expression analyses of osteoclast marker molecules revealed that osteoclasts in the scales were inactivated during the late and post-reproduction stages when the expression of CT and its receptor increased in female goldfish scales. Moreover, exogenous melatonin suppressed plasma calcium levels in female goldfish during their late reproductive stage in cases of increased melatonin receptor expression. Taken together, these results suggest that melatonin inactivates scale osteoclast resorption by increasing CT levels in the scales and prevents calcium leakage from the body during the late and post-reproductive stages of female goldfish.

Hypochlorous acid (HOCl) is an endogenous oxidant and chlorinating agent in mammals that is effective against a broad range of microorganisms. However, the effects of exogenous HOCl on biological processes have not been reported. In this study, the effects of highly purified slightly acidic hypochlorous acid water (HP-HAW) were investigated. After the safety of oral administration of HP-HAW was confirmed, the effects of HP-HAW on glucose homeostasis were assessed in mice. HP-HAW treatment significantly improved blood glucose levels in hyperglycemic condition. Based on the 16S rRNA sequencing, HP-HAW treatment significantly increased the diversity and changed the composition of gut microbiota by decreasing the abundance of genus Romboutsia in mice fed normal chow. In obese mice, HP-HAW administration tended to improve glucose tolerance. HP-HAW also attenuated memory impairments and changes N -methyl-d-aspartate (NMDA) receptor mRNA expression in obese mice. HP-HAW treatment suppressed Il-6 mRNA expression in the hippocampus in type 2 diabetic mice. Overall, these results support HP-HAW as a potential therapeutic agent to improve or prevent glucose tolerance and memory decline via gut microbiota alteration.

Previous studies in mice have reported that melanin-concentrating hormone (MCH) regulates bone calcification, an essential process in bone regeneration. However, the mechanisms by which MCH influences the activities of bone cells involved in calcification remain unclear. Goldfish scales, like mammalian bone, consist of osteoblasts, osteoclasts, and a calcified matrix, making regenerating goldfish scales a useful model for studying bone regeneration. In the present study, a single MCH treatment suppressed the expression of genes encoding proteins associated with osteoclast activity in cultured goldfish scales. Moreover, intraperitoneal administration of MCH decreased plasma calcium concentrations and tartrate-resistant acid phosphatase (TRAP) activity, an osteoclast activity marker, in goldfish 24 h after administration. Gene expression analysis suggested that MCH receptor 2 is involved in MCH-mediated regulation of calcification in goldfish scales. In contrast, continuous intraperitoneal administration of MCH elevated both alkaline phosphatase, an osteoblast marker, and TRAP activities in regenerating scales and resulted in decreased scale calcium levels. These results indicate that a single MCH treatment inhibits osteoclast activity in goldfish scales, leading to reduced plasma calcium levels, whereas prolonged MCH treatment affects both osteoclasts and osteoblasts in regenerating scales, thereby resulting in decreased calcium contents in the scales.

To examine the effects of heavy metals such as cadmium and mercury on calcium homeostasis, plasma calcium and calcitonin were measured in goldfish. Cadmium induced hypocalcemia both at 4 and at 8 days. In methylmercury-treated goldfish, the plasma calcium level increased at 2 days and then decreased at 8 days. The plasma calcitonin level increased in correspondence with the increased plasma calcium by methylmercury treatment, although cadmium did not cause a significant change. To elucidate the mechanism in detail, fish scales, which have both osteoclasts and osteoblasts and are similar to mammalian membrane bone, were used in the present study. We measured tartrate-resistant acid phosphatase (TRAP) and alkaline phosphatase (ALP) activity as respective indicators of activity in both types of cells. TRAP activity in the scales decreased by treatment of cadmium and methylmercury at 6 h incubation. Particularly, cadmium (even at 10(-13) M) significantly suppressed TRAP activity, suggesting that this system is utilized as an acute biosensor for cadmium. ALP activity decreased after exposures of 64 and 96 h, although the activity did not change after 6, 18, and 36 h. In addition, mRNA expression of the estrogen receptor and insulin-like growth factor 1, which participate in osteoblastic growth and differentiation, was less than the control values by treatment with both metals. This study demonstrates that mercury directly acts on the bone cells and influences calcium homeostasis and indicates that, in a short-term exposure, mercury has a different action from that of cadmium and induces hypercalcemia.

This study is the first to demonstrate that deep ocean water (DOW) has physiological significant effects on squid. After 36 h of rearing squids, those reared with DOW had significantly higher total and free cholesterol levels and lower alanine transaminase activity in hemolymph as compared with those reared with surface sea water (SSW). SSW rearing also resulted in 6.95% weight loss, while DOW rearing caused only 2.5% weight loss, which might be due to liver metabolism suppression. Furthermore, both monovalent (sodium, chloride, and potassium ions) and divalent (calcium, inorganic phosphorus, and magnesium ions) ions in hemolymph were elevated when reared with DOW compared to those when reared with SSW. A study of genes expressed in the brain revealed that five genes were specifically remarked in DOW rearing. Most altered genes were neuropeptides, including those from vasopressin superfamily. These neuropeptides are involved in cholesterol and/or mineral metabolisms and physiological significant effects on squid. This study is the first report the effects of DOW on cholesterol and mineral metabolism of squid and will contribute to squid aquaculture using DOW.