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Sulforaphane (SFaN) is a food-derived compound with several bioactive properties, including atherosclerosis, diabetes, and obesity treatment. However, the mechanisms by which SFaN exerts its various effects are still unclear. To elucidate the mechanisms of the various effects of SFaN, we explored novel SFaN-binding proteins using SFaN beads and identified acyl protein thioesterase 2 (APT2). We also found that SFaN binds to the APT2 via C56 residue and attenuates the palmitoylation of APT2, thereby reducing plasma membrane localization of APT2. This study reveals a novel bioactivity of SFaN as a regulator of APT2 protein palmitoylation. • Acyl-protein thioesterase 2 (APT2) is a novel SFaN-binding protein. • The isothiocyanate group of SFaN binds to the C56 of APT2. • SFaN attenuates the palmitoylation of APT2. [ABSTRACT FROM AUTHOR]

Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate various genes involved in cholesterol and fatty acid synthesis. In this study, we describe that naturally occurring isothiocyanate sulforaphane (SFaN) impairs fatty acid synthase promoter activity and reduces SREBP target gene (e.g., fatty acid synthase and acetyl-CoA carboxylase 1) expression in human hepatoma Huh-7 cells. SFaN reduced SREBP proteins by promoting the degradation of the SREBP precursor. Amino acids 595–784 of SREBP-1a were essential for SFaN-mediated SREBP-1a degradation. We also found that such SREBP-1 degradation occurs independently of the SREBP cleavage-activating protein and the Keap1-Nrf2 pathway. This study identifies SFaN as an SREBP inhibitor and provides evidence that SFaN could have major potential as a pharmaceutical preparation against hepatic steatosis and obesity. [ABSTRACT FROM AUTHOR]

Triokinase/FMN cyclase (Tkfc) is involved in fructose metabolism and is responsible for the phosphorylation of glyceraldehyde to glyceraldehyde-3-phosphate. In this study, we showed that refeeding induced hepatic expression of Tkfc in mice. Luciferase reporter gene assays using the Tkfc promoter revealed the existence of 2 hepatocyte nuclear factor 4α (HNF4α)-responsive elements (HNF4RE1 and HNF4RE2) and 1 carbohydrate-responsive element-binding protein (ChREBP)-responsive element (ChoRE1). Deletion and mutation of HNF4RE1 and HNF4RE2 or ChoRE1 abolished HNF4α and ChREBP responsiveness, respectively. HNF4α and ChREBP synergistically stimulated Tkfc promoter activity. ChoRE1 mutation attenuated but maintained HNF4α responsiveness, whereas HNF4RE1 and HNF4RE2 mutations abolished ChREBP responsiveness. Moreover, Tkfc promoter activity stimulation by ChREBP was attenuated upon HNF4α knockdown. Furthermore, Tkfc expression was decreased in the livers of ChREBP −/− and liver-specific HNF4 −/− (Hnf4α ΔHep) mice. Altogether, our data indicate that Tkfc is a target gene of ChREBP and HNF4α, and Tkfc promoter activity stimulation by ChREBP requires HNF4α. [ABSTRACT FROM AUTHOR]

Transcriptional co-activator with PDZ-binding motif (TAZ) plays versatile roles in the regulation of cell proliferation and differentiation. TAZ activity changes in response to the cellular environment such as mechanic and nutritional stimuli, osmolarity, and hypoxia. To understand the physiological roles of TAZ, chemical compounds that activate TAZ in cells are useful as experimental reagents. Kaempferol, TM-25659, and ethacridine are reported as TAZ activators. However, as each TAZ activator has a distinct property in cellular functions, additional TAZ activators are awaiting. We screened for TAZ activators and previously reported IB008738 as a TAZ activator that promotes myogenesis in C2C12 cells. In this study, we have characterized IBS004735 that was obtained in the same screening. IBS004735 also promotes myogenesis in C2C12 cells, but is not similar to IBS008738 in the structure. IBS004735 activates TAZ via Akt and has no effect on TAZ phosphorylation, which is the well-described key modification to regulate TAZ activity. Thus, we introduce IBS004735 as a novel TAZ activator that regulates TAZ in a yet unidentified mechanism. [ABSTRACT FROM AUTHOR]

This study explored the current implementation status of and opinions and concerns regarding suicide education at schools of social work in Japan. We conducted a survey of faculty members who taught at least one of the social work subjects. About half the respondents had given a lecture of some kind on suicide, and more than 80% agreed that suicide is an important topic to include in social work program curricula. However, more than half indicated they did not have enough knowledge or skills to teach students about suicide, and more than 60% were concerned about adverse psychological effects of suicide education on students. Our findings highlight the importance of providing faculty members with guidelines for teaching students about suicide. [ABSTRACT FROM AUTHOR]

Aim Although the female suicide rate in Japan is one of the highest among OECD countries, little has been done to assess the psychosocial and psychiatric characteristics of Japanese female suicide completers. This study aimed to examine sex differences in psychosocial and psychiatric characteristics of suicide completers using a psychological autopsy study method, and to identify female suicide factors and intervention points to prevent female suicides. Methods A semi-structured interview was conducted with close family members of adult suicide completers. The interview included questions regarding sociodemographic factors, suicide characteristics, previous suicidal behaviors and a family history of suicidal behaviors, financial problems, and physical/psychiatric problems. Fisher's exact test and the Student's t-test were used to explore sex differences in these survey items, and individual descriptive information of female suicide cases was also examined. Results Of the 92 suicide completers, 28 were female and 64 were male. Females had a significantly higher prevalence of a history of self-harm/suicide attempts ( P < 0.001). The prevalence of eating disorders was significantly higher among females than males ( P < 0.01). Conclusion The findings of this study highlight the importance of providing psychological and social support to caregivers of those who repeatedly attempt suicide and express suicidal thoughts, and to suggest the need to improve community care systems to be aware of suicide risk factors among female suicide attempters. [ABSTRACT FROM AUTHOR]

The development of the efficient screening system of detecting compounds that promote myogenesis and prevent muscle atrophy is important. Mouse C2C12 cells are widely used to evaluate myogenesis but the procedures of the assay are not simple and the quantification is not easy. We established C2C12 cells expressing the N-terminal green fluorescence protein (GFP) and the C-terminal GFP (GFP1–10 and GFP11 cells). GFP1–10 and GFP11 cells do not exhibit GFP signals until they are fused. The signal intensity correlates with the expression of myogenic markers and myofusion. Myogenesis-promoting reagents, such as insulin-like growth factor-1 (IGF1) and β-guanidinopropionic acid (GPA), enhance the signals, whereas the poly-caspase inhibitor, z-VAD-FMK, suppresses it. GFP signals are observed when myotubes formed by GFP1–10 cells are fused with single nuclear GFP11 cells, and enhanced by IGF1, GPA, and IBS008738, a recently-reported myogenesis-promoting reagent. Fusion between myotubes formed by GFP1–10 and GFP11 cells is associated with the appearance of GFP signals. IGF1 and GPA augment these signals, whereas NSC23766, Rac inhibitor, decreases them. The conditioned medium of cancer cells suppresses GFP signals during myogenesis and reduces the width of GFP-positive myotubes after differentiation. Thus the novel split GFP-based assay will provide the useful method for the study of myogenesis, myofusion, and atrophy. [ABSTRACT FROM AUTHOR]

The Hippo pathway was originally identified as the signaling that controls organ size in Drosophila, with the core architecture conserved in mammals. In the mammalian Hippo pathway, mammalian Ste20-like kinases (MST1/2) and large tumor suppressor kinases (LATS1/2) regulate transcriptional co-activators, Yes-associated protein (YAP1) and Transcriptional co-activator with a PDZ-binding motif (TAZ). The Hippo pathway was initially thought to be quite straightforward; however, the identification of additional components has revealed its inherent complexity. Regulation of YAP1 and TAZ is not always dependent on MST1/2 and LATS1/2. MST1/2 and LATS1/2 play various YAP1/TAZ-independent roles, while YAP1 and TAZ cross-talk with other signaling pathways. In this review we focus on YAP1 and TAZ and discuss their regulation, function, and the consequences of their dysregulation. [ABSTRACT FROM AUTHOR]

Highlights: [•] Sleep disturbances were significantly associated with suicide. [•] The association remained significant after adjusting for mental disorders. [•] The PARP of suicide associated with sleep disturbances was estimated to be 56.4%. [•] The PARP of suicide associated with mental disorders was estimated to be 35.3%. [•] Sleep disturbances could be considered an important target in suicide prevention. [ABSTRACT FROM AUTHOR]

The article presents a study on various factors of social workers' positions towards suicide. It states that the study mailed a self-administered questionnaire to participants who are registered with the Japanese Association of Certified Social Workers in Tokyo. It used Attitudes Toward Suicide Scale (ATTS) and multivariate analysis of covariance (MANCOVA). Results show that those who have a history of suicidal behavior had firm stands towards the right to suicide.

Background: Under-recognition of depression is common in many countries. Education of medical staff, focusing on their attitudes towards depression, may be necessary to change their behavior and enhance recognition of depression. Several studies have previously reported on attitudes toward depression among general physicians. However, little is known about attitudes of non-psychiatric doctors in Japan. In the present study, we surveyed non-psychiatric doctors' attitude toward depression. Methods: The inclusion criteria of participants in the present study were as follows: 1) Japanese non-psychiatric doctors and 2) attendees in educational opportunities regarding depression care. We conveniently approached two populations: 1) a workshop to depression care for non-psychiatric doctors and 2) a general physician-psychiatrist (GP) network group. We contacted 367 subjects. Attitudes toward depression were measured using the Depression Attitude Questionnaire (DAQ), a 20-item self-report questionnaire developed for general physicians. We report scores of each DAQ item and factors derived from exploratory factor analysis. Results: We received responses from 230 subjects, and we used DAQ data from 187 non-psychiatric doctors who met the inclusion criteria. All non-psychiatric doctors (n = 187) disagreed with "I feel comfortable in dealing with depressed patients' needs," while 60 % (n = 112) agreed with "Working with depressed patients is heavy going." Factor analysis indicated these items comprised a factor termed "Depression should be treated by psychiatrists" - to which 54 % of doctors (n = 101) agreed. Meanwhile, 67 % of doctors (n = 126) thought that nurses could be useful in depressed patient support. The three factors derived from the Japanese DAQ differed from models previously derived from British GP samples. The attitude of Japanese non-psychiatric doctors concerning whether depression should be treated by psychiatrists was markedly different to that of British GPs.Conclusions: Japanese non-psychiatric doctors believe that depression care is beyond the scope of their duties. It is suggested that educational programs or guidelines for depression care developed in other countries such as the UK are not directly adaptable for Japanese non-psychiatric doctors. Developing a focused educational program that motivates non-psychiatric doctors to play a role in depression care is necessary to enhance recognition and treatment of depression in Japan. [ABSTRACT FROM AUTHOR]

Background: Studies on attitudes toward suicide are of great interest to researchers worldwide. Although various instruments have been developed to measure attitudes toward suicide, psychometric properties of these instruments have not been systematically reviewed and organized.Aim: We aimed to identify valid, reliable and feasible attitudinal scales by systematically reviewing published articles on scale development and validation studies. In particular, this study focused on scales used for a wide range of populations to measure multidimensional attitudes toward suicide and related issues.Methods: Electronic searches of two databases, PubMed and PsychInfo, were performed. Scales with unique names were identified and listed after reviewing selected publications, and then evaluated for psychometric properties, multidimensionality and appropriateness for a wide range of populations.Results: A total of 2,210 publications were identified by the first electronic search. In the final review process of the selected publications, three scales — the Suicide Opinion Questionnaire (SOQ), Suicide Attitude Questionnaire (SUIATT) and Attitudes Toward Suicide (ATTS) — were identified.Conclusion: Each of these scales has its own characteristics and should be used in accordance with research purposes. [ABSTRACT FROM PUBLISHER]

Aims: Rest–activity rhythms of human beings generally synchronize to a 24-h time cue. Very few detailed research studies have examined rest–activity rhythms in patients with schizophrenia. The present study aimed to explore (i) rest–activity rhythms in patients with schizophrenia, and (ii) factors relevant to their rhythm characteristics. Methods: We selected only inpatients for this research, because the time cue for inpatients was considered more standardized than that of outpatients. Sixteen inpatients with schizophrenia wore an ActiTrac accelerometer-based activity monitor (IM Systems Inc., Baltimore, USA) for eight consecutive days to measure their activity. We used a χ2 periodogram to compute rest–activity rhythms from the activity data, whereby the χ2 value amplitude was regarded as an index of regularity. We conducted non-parametric tests to identify factors relevant to rhythm cycles and patterns. Results: Half of the participants exhibited prolonged rest–activity cycles, and 25% also had irregular rest–activity patterns defined by insufficient χ2 value amplitude, even though they were clearly under a 24-h time cue. Participants with misaligned rest–activity rhythms had attended daytime non-medical treatment programs less frequently, and had received more anti-anxiety/hypnotic medications than those with proper rhythms. Conclusion: Changes in rest–activity rhythms by optimizing pharmacological and non-pharmacological treatment could improve social adjustment or quality of life in patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Liver X receptors (LXR) α and β are a family of nuclear receptors that regulate lipogenesis by controlling the expression of the genes involved in the synthesis of fatty acids. MID1IP1 , which encodes MIG12, is a target gene of LXR. MIG12 induces fatty acid synthesis by stimulating the polymerization-mediated activation of acetyl-CoA carboxylase (ACC). Here, we show that LXR's activation stimulates ACC polymerization in HepG2 cells by increasing the expression of MIG12. A knockdown of MID1IP1 abrogated the stimulation completely. The mutations of MIG12's leucine-zipper domain reduced the interaction between MIG12 and ACC, thus decreasing the MIG12's capacity to stimulate ACC polymerization. These results indicate that LXR's activation stimulates lipogenesis not only through the induction of the genes encoding lipogenic enzymes but also through MIG12's stimulation of ACC polymerization. • LXR activation stimulates ACC polymerization. • MIG12 is required for the LXR activation-induced ACC polymerization. • The leucine-zipper domain of MIG12 is important for its function. [ABSTRACT FROM AUTHOR]

The purpose of the present paper was to examine the psychiatric symptom dimensions related to needs of care among patients with schizophrenia in hospital and in the community. Subjects were 217 patients with F2 ICD-10 diagnoses. Hospital patients included 102 inpatients (47.0%) in psychiatric long-term care units. Community patients included 115 outpatients (53.0%) living in their homes or residential facilities. Psychiatrists used the Brief Psychiatric Rating Scale (BPRS) to assess patients' psychiatric symptoms. Formal care providers assessed needs of care using a scale developed by the Committee on Case Management Guidelines for People with Mental Disabilities in Japan. Instrumental Activities of Daily Living (IADL) self-performance and difficulty were also measured using a scale from the Minimum Data Set–Home Care (MDS-HC). Multiple regression analyses were applied, using the symptom dimensions as dependent variables and needs of care as independent variables. Patient group (hospital or community) was also used as an independent variable. Hospital patients demonstrated more severe psychiatric symptoms and greater needs of care than community patients. Multiple regression analyses showed that the total needs of care were greater among male patients ( B = 0.142, P = 0.005), hospital patients ( B = 0.310, P < 0.001), patients with poor IADL self-performance ( B = 0.217, P = 0.047), and patients with severe negative symptoms ( B = 0.240, P = 0.002; R2 = 0.515). The present results suggested an association between negative symptoms and needs of care in schizophrenia. Hospital patients had greater needs of care, even though their psychiatric symptoms were controlled for. Further research should examine the relationships between psychiatric symptoms and needs of care in a cohort study following patients when hospitalized and when living in the community. [ABSTRACT FROM AUTHOR]

Muscle wasting or sarcopenia contributes to morbidity and mortality in patients with cancer, renal failure, or heart failure, and in elderly individuals. Na+-K+-2Cl− cotransporter 1 (NKCC1) is highly expressed in mammalian skeletal muscle, where it contributes to the generation of membrane ion currents and potential. However, the physiologic function of NKCC1 in myogenesis is unclear. We investigated this issue using the NKCC1 inhibitors bumetanide and furosemide, which are commonly used loop diuretics. NKCC1 protein levels increased during C2C12 murine skeletal myoblast differentiation, similarly to those of the myogenic markers myogenin and myosin heavy chain (MHC). NKCC1 inhibitors markedly suppressed myoblast fusion into myotubes and the expression of myogenin and MHC. Furthermore, phosphorylated and total NKCC1 levels were elevated in mouse skeletal muscles after 6 weeks' voluntary wheel running. Immunofluorescence analyses of myofiber cross-sections revealed more large myofibers after exercise, but this was impaired by daily intraperitoneal bumetanide injections (0.2 or 10 mg/kg/day). NKCC1 plays an essential role in myogenesis and exercise-induced skeletal muscle hypertrophy, and sarcopenia in patients with renal or heart failure may be attributable to treatment with loop diuretics. [ABSTRACT FROM AUTHOR]

Background: Previous research has produced conflicting findings concerning whether birthdays are associated with an increased risk of suicide. This study examined the association in Tokyo, Japan.Methods: Suicide data (ICD-10 codes X60-X84) for the period 2001-2010 were obtained from the Japanese Ministry of Health, Labour and Welfare. A time-stratified case-crossover design was used with conditional logistic regression analysis being performed to estimate within-subject 'birthday exposures' while controlling for meteorological conditions and public holidays.Results: There were 27,007 suicides in the study period. For males the 5 days before the birthday and the week after the birthday were associated with significantly higher odds for suicide with the odds ratio being highest on the actual birthday (OR =1.677, 95% CI: 1.294, 2.172). For females, significantly higher odds for completed suicide were observed 7-11 days before the birthday. Stratified analyses showed different at risk time patterns among men from different age groups, and that married men had higher odds for suicide on, and for the 4 days before and in the 2 weeks after their birthday.Limitations: We lacked detailed information on suicides which would have enabled a better understanding of the observed associations.Conclusions: Birthdays are associated with an increased risk for suicide in Tokyo, Japan. Health professionals who work with individuals at risk of suicide should be made aware that birthdays are associated with an elevated suicide risk. This information should also be communicated in wider suicide prevention campaigns. [ABSTRACT FROM AUTHOR]

Suicide is a global public health problem and solutions to it can be found only through a global dialog. The suicide rate in Japan has been alarming, but Japan has made substantial efforts to reduce this rate, making prevention a high priority. This report reviews the developmental stages of a comprehensive policy of suicide prevention in Japan from 1998 to 2013. Our review suggests that suicide prevention activities were facilitated by the 2006 Basic Act for Suicide Prevention and the 2007 General Principles of Suicide Prevention Policy. Along with the establishment of a Special Fund program for local governments, the Basic Act and General Principles led to the development of a comprehensive and multi-sector approach to suicide prevention. Suicide rates in Japan, especially among middle-aged men, decreased consistently after 2009, suggesting that the initiatives were effective. Continuous monitoring is needed to evaluate Japan's suicide prevention policy. [ABSTRACT FROM AUTHOR]