Coordinated linear and rotational movements of endothelial cells compartmentalized by VE-cadherin drive angiogenic sprouting.

Angiogenesis is a sequential process to extend new blood vessels from preexisting ones by sprouting and branching. During angiogenesis, endothelial cells (ECs) exhibit inhomogeneous multicellular behaviors referred to as "cell mixing," in which ECs repetitively exchange their relative positions, but the underlying mechanism remains elusive. Here we identified the coordinated linear and rotational movements potentiated by cell-cell contact as drivers of sprouting angiogenesis using in vitro and in silico approaches. VE-cadherin confers the coordinated linear motility that facilitated forward sprout elongation, although it is dispensable for rotational movement, which was synchronous without VE-cadherin. Mathematical modeling recapitulated the EC motility in the two-cell state and angiogenic morphogenesis with the effects of VE-cadherin-knockout. Finally, we found that VE-cadherin-dependent EC compartmentalization potentiated branch elongations, and confirmed this by mathematical simulation. Collectively, we propose a way to understand angiogenesis, based on unique EC behavioral properties that are partially dependent on VE-cadherin function.

L-Fucose Suppresses Lipid Accumulation via the AMPK Pathway in 3T3-L1 Adipocytes.

L-fucose (Fuc), a monosaccharide with different biological functions in various organisms, exhibits potent anti-obesity effects in obese mice. However, the mechanisms underlying its anti-obesity effects remain largely unknown. In this study, we aimed to investigate the effects of Fuc on lipid metabolism and insulin signaling in 3T3-L1 adipocytes. We found that Fuc treatment suppressed lipid accumulation during adipocyte differentiation. Additionally, Fuc treatment enhanced the phosphorylation of AMP-activated kinase (AMPK) and its downstream pathways, responsible for the regulation of fatty acid oxidation and lipolysis. Furthermore, Fuc-induced activation of the AMPK pathway was diminished by the AMPK inhibitor Compound C, and Fuc treatment considerably promoted glucose uptake via Akt activation in an insulin-resistant state. These findings provide a basis for elucidating the mechanism underlying the anti-obesity effect of Fuc, which may, in the future, be considered as a therapeutic compound for treating obesity and related diseases.

The Philippines stingless bee propolis promotes hair growth through activation of Wnt/ß-catenin signaling pathway.

Although hair loss is not a horrible disease, it sometimes reduces the patients' quality of life (QOL) and increases their mental stress. Currently, there is no effective treatment for hair loss. It is known that honeybee propolis has various biological activities, including stimulating the proliferation of hair matrix keratinocytes. However, little is known with the hair promoting activity of stingless bee propolis. Hence, this study investigates the hair growth-promoting activity of Philippines stingless bee propolis extract and the underlying a molecular mechanism of promoting hair growth. For the evaluation of hair growth stimulating activity, 99.5% ethanolic extract of Philippines stingless bee propolis is examined using the simple shaving model in C57BL/6N mice. Melaninization of dorsal skin and histological analysis of hair follicles (HFs) revealed that propolis promotes hair growth by stimulating HFs development. The expression of mRNA (Wnt3a, Ctnnb1/ß-catenin, Lef1, and Bmp2) and protein (WNT3A and ß-catenin) of selected Wnt/ß-catenin associated genes explains Philippines stingless bee propolis promoting HFs development by activating Wnt/ß-catenin signaling pathway. These results suggest that the treatment of propolis strongly promotes hair growth by stimulating the development of HFs via activation of Wnt/ß-catenin signaling pathway. This further indicates the potential of Philippines stingless bee propolis as a novel promising agricultural product for hair growth.

Peptidomic analysis characterising proteolysis in thaw-aging of beef short plate.

Recent studies have suggested that thaw-aging can improve sensory attributes of freeze-thawed meat. Acceleration of proteolysis is expected to promote tenderisation and improve taste; however, the details of protein degradation, including substrate proteins and cleavage sites, remain unclear. Here, we report a time course overview of the peptidome of beef short plates during thaw-aging. The accelerated degradation of key proteins for meat tenderisation, such as troponin T and desmin, was confirmed. Additionally, 11 cleavage sites in troponin T related to taste-active peptide generation were identified. Terminome analysis showed that the contribution of each protease varies depending on the substrate proteins and the thaw-aging period. Based on our results; proteases, not only calpains, but also others contributed to the degradation of myofibrillar proteins. The techniques employed indicate that meat proteolysis during thaw-aging is not constant but dynamic.

The Effects of Brown Algae-Derived Monosaccharide L-Fucose on Lipid Metabolism in C57BL/6J Obese Mice.

Obesity is a global public health problem and a risk factor for several metabolic disorders as well as cancer. In this study, we investigated the effects of L-fucose on lipid metabolism through chronic and acute in vivo experiments in mice. In the chronic test, mice were fed a high-calorie diet (HCD) containing 0.0001%, 0.001%, 0.01%, and 0.1% L-fucose for one month. The L-fucose supplementation inhibited body weight and visceral fat mass gain in HCD-fed mice. The results of the acute test showed that L-fucose increased the ratio of serum high molecular weight adiponectin and enhanced glucose and lipid catabolism. Furthermore, L-fucose also decreased the expression of adipogenic genes (peroxisome proliferator-activated receptor γ and cluster of differentiation 36). In conclusion, this study provides a new approach to combat obesity and the related diseases.

Peptidomic Analysis of a Disintegrated Surimi Gel from Deep-Sea Bonefish Pterothrissus gissu.

Surimi gel is a commonly found gelled product in Japan. Disintegration of the surimi gel is mainly caused by proteolytic degradation of the myosin heavy chain (MHC) under an inappropriate heating process. Many studies have reported the decrease in MHC in the disintegrated surimi gel but the mechanistic details of this degradation remain unclear. This study employed peptidomic analysis of disintegrated surimi gels from deep-sea bonefish Pterothrissus gissu to reveal the MHC cleavage causing gel disintegration. More peptides derived from an MHC rod were found in the disintegrated P. gissu surimi gels than in the integrated gel. Most MHC peptides were derived from the Src homology 3 domain or near the skip residues. The results of the terminome analysis suggest that the catalytic type of the proteases is responsible for light meromyosin cleavage activated at ∼35 °C. These results showed the temperature-dependent cleavage of the MHC rod, causing disintegration of the P. gissu surimi gel.

Tumor-suppressing potential of stingless bee propolis in in vitro and in vivo models of differentiated-type gastric adenocarcinoma.

The protective property of propolis across a wide spectrum of diseases has long been realized, yet the anti-tumor efficacy of this bioactive substance from Philippine stingless bees has remained poorly understood. Here, we showed the tumor-suppressing potential of crude ethanolic extract of Philippine stingless bee propolis (EEP) in in vitro models of gastric cancer highlighting the first indication of remarkable subtype specificity towards differentiated-type human gastric cancer cell lines but not the diffuse-type. Mechanistically, this involved the profound modulation of several cell cycle related gene transcripts, which correlated with the prominent cell cycle arrest at the G0/G1 phase. To reinforce our data, a unique differentiated-type gastric cancer model, A4gnt KO mice, together with age-matched 60 week-old C57BL/6 J mice were randomly assigned to treatment groups receiving distilled water or EEP for 30 consecutive days. EEP treatment induced significant regression of gross and histological lesions of gastric pyloric tumors that consistently corresponded with specific transcriptional regulation of cell cycle components. Also, the considerable p21 protein expression coupled with a marked reduction in rapidly dividing BrdU-labeled S-phase cells unequivocally supported our observation. Altogether, these findings support the role of Philippine stingless bee propolis as a promising adjunct treatment option in differentiated-type gastric cancer.

A Novel Analysis of the Peptide Terminome Characterizes Dynamics of Proteolytic Regulation in Vertebrate Skeletal Muscle Under Severe Stress.

In healthy cells, proteolysis is orderly executed to maintain basal homeostasis and normal physiology. Dyscontrol in proteolysis under severe stress condition induces cell death, but the dynamics of proteolytic regulation towards the critical phase remain unclear. Teleosts have been suggested an alternative model for the study of proteolysis under severe stress. In this study, horse mackerel (Trachurus japonicus) was used and exacerbated under severe stress conditions due to air exposure. Although the complete genome for T. japonicus is not available, a transcriptomic analysis was performed to construct a reference protein database, and the expression of 72 proteases were confirmed. Quantitative peptidomic analysis revealed that proteins related to glycolysis and muscle contraction systems were highly cleaved into peptides immediately under the severe stress. Novel analysis of the peptide terminome using a multiple linear regression model demonstrated profiles of proteolysis under severe stress. The results indicated a phase transition towards dyscontrol in proteolysis in T. japonicus skeletal muscle during air exposure. Our novel approach will aid in investigating the dynamics of proteolytic regulation in skeletal muscle of non-model vertebrates.