Cloning of a cDNA for the Human Cell Adhesion Kinase β

Cell adhesion kinase beta (CAKbeta) is the second protein-tyrosine kinase (PTK) of the focal adhesion kinase (FAK) subfamily with large N- and C-domains in addition to the central kinase domain but without Src homology 2 and 3 (SH-2 and SH-3) domains. In this paper, cloning and sequencing of a cDNA encoding human CAKβ are described. A full-length clone (clone B) contained 4,157- base pairs of human CAKβ cDNA including 243-base pairs of the 5\u27-untranslated sequence and 881-base pairs of the 3\u27-untranslated sequence with a polyadenyla-tion signal (ATTAAA). The clone B of human CAKβ cDNA has an open read-ing frame encoding 1009 amino acid residues ; the human CAKβ has the same number of amino acid residues in the N-, C-, and kinase-domains as rat CAKβ . The amino acid sequence of human CAKβ is 95.4% identical with that of rat CAKβ . The species difference is most prominent in the C-domain. All three previously-recognized, subfamily-specific residues in the kinase domains of FAK and the rat CAKβ are also found in the human CAKβ . The residues V??? and A???, which have been considered to be characteristic to CAKβ , are found to be conserved also in the human CAK? . It has been postulated that CAKβ is important as a docking protein. The autophosphorylation site and also the ligand site to the SH-2 domains of the Src-family PTKs, Y???AEI, are found to be conserved in the human CAKβ . The ligand sequence for the Grb2 SH-2 domain, Y???HNV of the rat CAKβ , is found functionally conserved in the human CAKβ , Y???LNV. The third ligand sequence, E???PPPKPSR, participating in the binding to the SH-3 domains of pp130cas and Efs, is also found conserved in the human CAKβ . The extreme N- terminal 88 amino acid residues of the rat CAKβ were previously found entirely different from FAK and found unique to CAK? . Ninety four percent of those 88 residues in the human CAKβ are found identical with the rat CAKβ . This high sequence homology strongly suggeststhat this region is involved in the specific function of CAKβ different from FAK

Effect of oral intake of royal jelly on endothelium function in hemodialysis patients: study protocol for multicenter, double-blind, randomized control trial

Background: Hemodialysis (HD) is a common renal replacement therapy for patients with renal failure. Cardiovascular and cerebrovascular diseases are known to shorten survival periods and worsen the quality of life of HD patients. Atherosclerosis is a major cause of vascular diseases, and various factors such as abnormality of lipid metabolism and increased macrophage activity, oxidative stress, and endothelial dysfunction are associated with its pathogenesis and progression. Further, endothelial stem cells (ESCs) have been reported to play important roles in endothelial functions. Royal jelly (RJ) affects atherosclerosis- and endothelial function-related factors. The main aim of this trial is to investigate whether oral intake of RJ can maintain endothelial function in HD patients. In addition, the effects of RJ intake on atherosclerosis, ESC count, inflammation, and oxidative stress will be analyzed.Methods: This will be a multicenter, prospective, double-blind, randomized controlled trial. We will enroll 270 participants at Nagasaki Jin Hospital, Shinzato Clinic Urakami, and Maeda Clinic, Japan. The participants will be randomized into RJ and placebo groups. The trial will be conducted according to the principles of the Declaration of Helsinki, and all participants will be required to provide written informed consent. The RJ group will be treated with 3600 mg/day of RJ for 24 months, and the placebo group will be treated with starch for 24 months. The primary endpoint will be the change in flow-mediated dilation (FMD), a parameter of endothelium function, from the time before treatment initiation to 24 months after treatment initiation. The secondary and other endpoints will be changes in FMD; ESC count; serum levels of vascular endothelial cell growth factor, macrophage colony-stimulating factor, 8-hydroxydeoxyguanosine, and malondialdehyde; the incidence of cardiovascular diseases, cerebrovascular diseases, and stenosis of blood access; and safety.Discussion: This trial will clarify whether oral intake of RJ can maintain endothelial function and suppress the progression of atherosclerosis in HD patients. In addition, it will clarify the effects of RJ on ESCs, oxidative stress, and angiogenic activity in blood samples.Trial registration: The Japan Registry of Clinical Trials jRCTs071200031. Registered on 7 December 2020

Effect of oral intake of royal jelly on endothelium function in hemodialysis patients: study protocol for multicenter, double-blind, randomized control trial

BACKGROUND: Hemodialysis (HD) is a common renal replacement therapy for patients with renal failure. Cardiovascular and cerebrovascular diseases are known to shorten survival periods and worsen the quality of life of HD patients. Atherosclerosis is a major cause of vascular diseases, and various factors such as abnormality of lipid metabolism and increased macrophage activity, oxidative stress, and endothelial dysfunction are associated with its pathogenesis and progression. Further, endothelial stem cells (ESCs) have been reported to play important roles in endothelial functions. Royal jelly (RJ) affects atherosclerosis- and endothelial function-related factors. The main aim of this trial is to investigate whether oral intake of RJ can maintain endothelial function in HD patients. In addition, the effects of RJ intake on atherosclerosis, ESC count, inflammation, and oxidative stress will be analyzed. METHODS: This will be a multicenter, prospective, double-blind, randomized controlled trial. We will enroll 270 participants at Nagasaki Jin Hospital, Shinzato Clinic Urakami, and Maeda Clinic, Japan. The participants will be randomized into RJ and placebo groups. The trial will be conducted according to the principles of the Declaration of Helsinki, and all participants will be required to provide written informed consent. The RJ group will be treated with 3600 mg/day of RJ for 24 months, and the placebo group will be treated with starch for 24 months. The primary endpoint will be the change in flow-mediated dilation (FMD), a parameter of endothelium function, from the time before treatment initiation to 24 months after treatment initiation. The secondary and other endpoints will be changes in FMD; ESC count; serum levels of vascular endothelial cell growth factor, macrophage colony-stimulating factor, 8-hydroxydeoxyguanosine, and malondialdehyde; the incidence of cardiovascular diseases, cerebrovascular diseases, and stenosis of blood access; and safety. DISCUSSION: This trial will clarify whether oral intake of RJ can maintain endothelial function and suppress the progression of atherosclerosis in HD patients. In addition, it will clarify the effects of RJ on ESCs, oxidative stress, and angiogenic activity in blood samples. TRIAL REGISTRATION: The Japan Registry of Clinical Trials jRCTs071200031.  Registered on 7 December 2020