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Background: The efficacy of the unified protocol of the transdiagnostic treatment for emotional disorders (UP) has been poorly studied in patients with depressive disorders. This study aimed to examine the efficacy of UP for improving depressive symptoms in patients with depressive and/or anxiety-related disorders. Methods: This assessor-blinded, randomized, 20-week, parallel-group, superiority study compared the efficacy of the UP with treatment-as-usual (UP-TAU) v. wait-list with treatment-as-usual (WL-TAU). Patients diagnosed with depressive and/or anxiety disorders and with depressive symptoms participated. The primary outcome was depressive symptoms assessed by GRID-Hamilton depression rating scale (GRID-HAMD) at 21 weeks. The secondary outcomes included assessor-rated anxiety symptoms, severity and improvement of clinical global impression, responder and remission status, and loss of principal diagnosis. Results: In total, 104 patients participated and were subjected to intention-to-treat analysis [mean age = 37.4, s.d. = 11.5, 63 female (61%), 54 (51.9%) with a principal diagnosis of depressive disorders]. The mean GRID-HAMD scores in the UP-TAU and WL-TAU groups were 16.15 (s.d. = 4.90) and 17.06 (s.d. = 6.46) at baseline and 12.14 (s.d. = 5.47) and 17.34 (s.d. = 5.78) at 21 weeks, with a significant adjusted mean change difference of −3.99 (95% CI −6.10 to −1.87). Patients in the UP-TAU group showed significant superiority in anxiety and clinical global impressions. The improvement in the UP-TAU group was maintained in all outcomes at 43 weeks. No serious adverse events were observed in the UP-TAU group. Conclusions: The UP is an effective approach for patients with depressive and/or anxiety disorders. [ABSTRACT FROM AUTHOR]

Abstract: Cysteine proteases are attractive drug targets due to their involvement in a wide variety of diseases. To evaluate the potential of a particular protease as a drug target, use of a reagent that controls activity of the protease is indispensable. In this context, we have developed a catch-and-release reagent that first forms a covalent bond with the active center thiol of a cysteine protease to suppress its activity and then is removed by UV-irradiation to release the parent active protease. In this paper, the design and synthesis of a catch-and-release reagent of thiols are described. Its application to caging (catch) and UV-induced uncaging (release) of a model peptide derived from an active site of caspase-9 and introduction of a recognition moiety on the reagent are also reported. [Copyright &y& Elsevier]

Abstract: A previous study led to the isolation of antimicrobial peptides belonging to the temporin and brevinin-2 families from a pooled extract of the skin of adult specimens of the Japanese mountain brown frog Rana ornativentris Werner 1903. In order to ascertain whether individual frogs expressed the full complement of temporin genes, we individually cloned cDNAs encoding the temporin precursors from total RNA extracted from the skins of 12 frogs by RT-PCR using a set of preprotemporin-specific primers. All the specimens examined contained mRNAs directing the synthesis of the novel, but inactive, temporin-1Oe (ILPLLGNLLNGLL·NH2). Nucleotide sequence analysis revealed marked polymorphism among individual frogs. Twenty-seven distinct preprotemporin-1Oe mRNAs were identified that contained synonymous substitutions in the antimicrobial peptide region and both synonymous and non-synonymous substitutions in the signal peptide and intervening sequence regions. Up to eight preprotemporin-1Oe mRNA variants were found within a single frog. In addition, several cDNAs encoding preprotemporin-1Oa and -1Ob and a single cDNA encoding preprotemporin-1Oc were characterized. Peptidomic analysis of norepinephrine-stimulated skin secretions revealed the presence of temporin-1Oe, temporin-1Of (SLILKGLASIAKLF·NH2), temporin-1Og (FLSSLLSKVVSLFT·NH2), four members of the ranatuerin-2 family and one member of the palustrin-2 family in addition to previously characterized temporin and brevinin-2 peptides. [Copyright &y& Elsevier]

Abstract: Sphingolipids, recognized as membrane constructs and as key signaling molecules, have been studied to examine intracellular function. Some caged sphingolipids that release parent sphingolipids after exposure to UV-irradiation have been previously developed, but caged ceramide has yet to be reported. In this study, we report the design and synthesis of a caged ceramide. Photo-irradiation experiment clarified that the caged ceramide can be successfully converted to the parent ceramide by UV-irradiation. Introduction of an alkyne-handle moiety for further modification of the caged ceramide is also reported. [Copyright &y& Elsevier]

Abstract: In the field of chemical biology, methods for controlling peptidyl function by a stimulus are attracting increasing attention. Recently, we reported a stimulus-responsive peptide, which can be cleaved after exposure to a stimulus. In this study, we developed a FRET-based assay system to estimate the kinetics of the stimulus-induced processing (peptide bond cleavage) reaction. Based on the FRET system, it was clarified that introduction of a sterically less-hindered or polar residue at the position adjacent to the stimulus-responsive amino acid accelerates the processing reaction. [Copyright &y& Elsevier]

Affective styles are assumed to play an important role in maintaining negative affect, including anxiety and depression. However, little is known about the longitudinal relationship between affective styles and symptoms. Therefore, we conducted a longitudinal study to examine the influence of affective styles, assessed using the Affective Style Questionnaire, on anxiety and depression among clinical populations in Japan. Using an online survey, 1521 participants (406 with major depressive disorder; 479 with one or more anxiety disorders; and 636 with both) answered the Affective Style Questionnaire and measures of emotion regulation, anxiety and depression symptoms. Data were collected twice over 2 months. Confirmatory factor analyses replicated the same four-factor structure found in a previous sample of Japanese university students. Hierarchical regression analyses revealed that the affective styles had a slightly greater effect on anxiety symptoms but not on depression compared to other common emotion regulation strategies, such as suppression and reappraisal measured by the Emotion Regulation Questionnaire (ERQ). Limitations of this study were that it used online surveys, in which, participants' diagnostic statuses were based on unverifiable self-reports. In conclusion, the association of affective styles with anxiety and depression among the clinical populations was prospectively confirmed. Further study is needed to examine the association considering the combination or profiles of affective styles among different emotional disorders., (© 2022 John Wiley & Sons, Ltd.)

Yes-associated protein 1 (YAP1) and its paralogue PDZ-binding motif (TAZ) play pivotal roles in cell proliferation, migration, and invasion, and abnormal activation of these TEAD transcriptional coactivators is found in diverse cancers in humans and mice. Targeting YAP1/TAZ signaling is thus a promising therapeutic avenue but, to date, few selective YAP1/TAZ inhibitors have been effective against cancer cells either in vitro or in vivo. We screened chemical libraries for potent YAP1/TAZ inhibitors using a highly sensitive luciferase reporter system to monitor YAP1/TAZ-TEAD transcriptional activity in cells. Among 29 049 low-molecular-weight compounds screened, we obtained nine hits, and the four of these that were the most effective shared a core structure with the natural product alantolactone (ALT). We also tested 16 other structural derivatives of ALT and found that natural ALT was the most efficient at increasing ROS-induced LATS kinase activities and thus YAP1/TAZ phosphorylation. Phosphorylated YAP1/TAZ proteins were subject to nuclear exclusion and proteosomic degradation such that the growth of ALT-treated tumor cells was inhibited both in vitro and in vivo. Our data show for the first time that ALT can be used to target the ROS-YAP pathway driving tumor cell growth and so could be a potent anticancer drug., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

This paper discusses how positive emotions can help maintain and improve mental health during the COVID-19 outbreak, taking into account examples of social interaction and positive psychology research efforts in Japanese context. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Objective: Although family involvement in the treatment of obsessive-compulsive disorder (OCD) produces a reduction in OCD symptoms and has significant effects on global functioning, few studies have focused on family intervention as part of OCD treatment in Japan. This study aims to examine the feasibility and efficacy of the family-based exposure and response prevention (FERP) program for adult patients with OCD and their family members. Design: Randomized controlled pilot study. Methods: A total of 18 outpatients aged 18-65 years with a primary diagnosis of OCD and one family member of each patient were randomized to an intervention group or a control group (1:1). The intervention group received the FERP program, which consisted of 16 weekly face-to-face cognitive behavioral therapy (CBT) sessions, including eight joint sessions with family members, in addition to treatment-as-usual (TAU). The control group received TAU alone. The primary outcome was the alleviation of OCD symptoms, as measured by changes in the total Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score from baseline to posttreatment. Analyses were provided on an intention-to-treat basis, and linear mixed models were used to test for significant group differences. Results: After 16 weeks, patients allocated to the FERP program showed improvement in OCD symptom severity, as measured by the total change score of the Y-BOCS (Hedges' g = -1.58), as compared to the control group. Two patients (22.2%) in the FERP group reached remission, and five patients (55.6%) in the FERP group achieved treatment response. Clinical global improvement measured by the FAS-SR scores, K6 scores, and CGI-S scores was also observed (Hedges' g = -1.35, -1.25, and -1.26, respectively) in the FERP group as compared to the control group. The dropout rate from the study was low ( n = 2, 11.8%), and no adverse events were reported in the FERP group. Conclusion: Our results suggest that FERP may be an effective program for reducing patients' OCD symptoms. Clinical Trial Registration: www.umin.ac.jp/ctr/, identifier UMIN000021763., (Copyright © 2020 Kobayashi, Kanie, Nakagawa, Takebayashi, Shinmei, Nakayama, Yamaguchi, Nakayama, Hirabayashi, Mimura and Horikoshi.)

We carried out structure-activity relationship study on anti-cancer effects of naftopidil (1) and its metabolites, resulted in identification of 1-(4-hydroxy-2-methoxyphenyl)piperazin-1-yl)-3-(naphthalen-1-yloxy) propan-2-ol (2, HUHS190), a major human metabolite of 1, which exhibited the most selective toxicities between against normal and cancer cells (Table 1). 2 was more hydrophilic compared to 1, was enough to be prepared in high concentration solution of more than 100 μM in saline for an intravesical instillation drug. Moreover, serum concentration of 2 was comparable to that of 1, an oral preparation drug, after oral administration at 32 mg/kg (Fig. 3). Both of 1 and 2 showed broad-spectrum anti-cancer activities in vitro, for example, 1 and 2 showed inhibitory activity IC 50  = 21.1 μM and 17.2 μM for DU145, human prostate cancer cells, respectively, and IC 50  = 18.5 μM and 10.5 μM for T24 cells, human bladder cancer cells. In this study, we estimated anticancer effects of 2 in a bladder cancer model after intravesical administration similar to clinical cases. A single intravesical administration of 2 exhibited the most potent inhibitory activities among the clinical drugs for bladder cancers, BCG and Pirarubicin, without obvious side effects and toxicity (Fig. 4). Thus, HUHS190 (2) can be effective for patients after post-TURBT therapy of bladder cancer without side effects, unlike the currently available clinical drugs., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: Emotion regulation utilizing positive emotion during negative emotional states might be one of the effective ways to alleviate depression and anxiety problems among people with emotional disorders. This study examined the psychometric properties and incremental validity of the Positive Emotion In Distress Scale (PEIDS), a newly developed self-report scale, in a sample of university students in Japan., Design and Methods: To examine the psychometric properties of the PEIDS, the scale was completed by Japanese university students (396 men and 363 women; mean age of 19.92). Participants additionally answered the Emotion Regulation Questionnaire, Rumination and Reflection Questionnaire - Shorter Version, Affective Style Questionnaire, Positive and Negative Affective Schedule, and Hospital Anxiety and Depression Scale. The survey was conducted at two time points separated by 1 month to assess test-retest reliability and validity of the PEIDS., Results: Exploratory and confirmatory factor analyses confirmed a one-factor structure. Reliability was confirmed by high internal consistency and test-retest stability; the convergent and discriminant validity was confirmed by correlations with related and unrelated variables. The results of hierarchical regression analyses demonstrated that positive emotion in distress might predict depression above and beyond the effect of baseline depression and other common emotion regulation strategies., Conclusions: The PEIDS showed acceptable reliability and validity within young adults and a non-clinical population in Japan. Further research will be needed to examine the effect of positive emotion among clinical populations., Practitioner Points: Previous research suggests that positive emotions play a key role in recovery from depression and anxiety problems through some forms of psychotherapy. The Positive Emotion In Distress Scale (PEIDS) measures individual differences regarding the extent to which people can experience positive emotions in negative emotional states. Results suggested that the subjective rating of the ability to experience positive emotions in distress might alleviate depression prospectively but not anxiety problems. The effect of positive emotion in distress demonstrated to have beyond the effects of other emotion regulation strategies., (© 2018 The British Psychological Society.)

Red koji, which refers the solid culture grown koji mold on the steamed rice, is one of the ingredients of Asian fermented foods including the Japanese spirit shochu. This study was aimed at elucidating the characteristic flavor and key volatile compounds of red koji-shochu as well as the mechanism of their formation. Sensory evaluation showed that red koji-shochu has the distinctive flavors cheese, sour, milky, and oily. Fifteen key volatile compounds of red koji-shochu were identified by gas chromatography-mass spectrometry and high-performance liquid chromatography, and by comparison between red koji-shochu and white koji-shochu, as another typical shochu. The mash analysis revealed that ketone compounds and short-chain acids derive from red koji. Furthermore, although other key compounds were produced by yeast, it is highly likely that their concentrations were affected directly or indirectly by the high activities of protease and lipase in red koji., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

To assess the quality of life (QoL) of children in Japan with inborn errors of metabolism (IEM) as well as of their parents, we reviewed 23 previous studies published in Japanese and 1 published in English, focusing on the difficulties they encounter in daily life, the factors associated with these difficulties, and their QoL. We divided the difficulties and associated factors into three developmental stages. At the infant stage, individuals with IEM tend to be at high risk of hypercatabolism. Their parents suffered anxiety and distress because of the child's diet therapy and regarded the parents' support group as an essential presence, particularly given that IEM is a rare disease. At the school-age stage, as their sphere of social relationships expanded, children with IEM became nervous about being compared with healthy children of their own age because of their diet therapy. At the adolescence-to-adulthood stage, the children suffered medically, economically, and socially. Even in the absence of any IEM symptoms, the children's QoL was affected by the demands associated with the metabolic disorder, such as diet and treatment. The psychological health of their caregivers was also poor. To improve the QoL of children with IEM and of their parents, future comprehensive quantitative and qualitative studies of their QoL and of their subjective support needs are required. Additionally, the specific factors related to the QoL of such individuals need to be explored in large population-based statistical studies.

Objectives: The families of these children experience distress both at the time of diagnosis and afterward. A top priority is to understand family empowerment, family function, and family members' quality of life (QoL) and to effectively support these families in Japan. The objective of this study was to assess the actual conditions of families living with children having DDs and to explore the factors associated with family empowerment and parents' QoL., Methods: We surveyed ninety-three parents (78 mothers, 15 fathers) from 78 families which lived with children with DDs in the capital region of Japan. We assessed two main outcomes using the Japanese versions of the following instruments: Family Empowerment Scale (FES), World Health Organization Quality of Life 26 (WHOQOL26), and other six outcomes. Correlation and multiple regression analyses were conducted., Results: No medication, cooperation with child rearing, assistance from a developmental support center, solved problems related to child rearing, and higher scores in Problem Solving contributed to higher FES scores. Higher WHOQOL26 scores were related to being a full-time housewife, higher self-esteem, no developmental support, a broad emotional support network, higher scores in Problem Solving and Role Function, and lower scores in Affective Reaction and General Function., Conclusions: We revealed that family empowerment and QoL of parents rearing children with DDs in Japan were affected by various subscales of family function and other family attributes. Effective interventions for improving family empowerment and QoL should be researched in the future.

This study was conducted using a web-based survey and bidding game in contingent valuation method to evaluate consumer preferences for packaging with less material. Results revealed that people who live in a municipality implementing unit-based pricing of waste have a higher willingness-to-pay (WTP) for a product. Economic instruments can affect the purchase of products with reduced packaging because a higher disposal cost increases the attractiveness of source reduction. However, unit-based pricing combined with plastic separation for recycling reduces WTP. This result suggests that recycling policy weakens the effect of economic instruments on source reduction of waste., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Maillard reaction peptides (MRPs) contribute to taste, aroma, colour, texture and biological activity. However, peptide degradation or the cross-linking of MRPs in the Maillard reaction has not been investigated clearly. A peptide of LEKFD, a part of β-lactoglobulin, was heated at 110 °C for 24h with glucose and the reaction products were analysed by HPLC with ODS, ESI-MS, ESI-MS/MS and HPLC with gel-filtration column and DAD detector. In the HPLC fractions, an imminium ion of LEK*FD, a pyrylium ion or a hydroxymethyl furylium ion of LEK*FD, and KFD and EK were detected by ESI-MS. Therefore, those products may be produced by the Maillard reaction. The molecular orbital of glycated LEKFD at the lysine epsilon-amino residue with Schiff base form was calculated by MOPAC. HPLC with gel-filtration column showed cross-linking and degradation of peptides., (Copyright © 2013 Elsevier Ltd. All rights reserved.)