Multipotent adult hippocampal progenitor cells maintained as neurospheres favor differentiation toward glial lineages

Adult hippocampal progenitor cells (AHPCs) are generally maintained as a dispersed monolayer population of multipotent neural progenitors. To better understand cell-cell interactions among neural progenitors and their influences on cellular characteristics, we generated free-floating cellular aggregates, or neurospheres, from the adherent monolayer population of AHPCs. Results from in vitro analyses demonstrated that both populations of AHPCs were highly proliferative under maintenance conditions, but AHPCs formed in neurospheres favored differentiation along a glial lineage and displayed greater migrational activity, than the traditionally cultured AHPCs. To study the plasticity of AHPCs from both populations in vivo, we transplanted GFP-expressing AHPCs via intraocular injection into the developing rat eyes. Both AHPC populations were capable of surviving and integrating into the developing host central nervous system, but considerably more GFP-positive cells were observed in the retinas transplanted with neurosphere AHPCs, compared to adherent AHPCs. These results suggest that the culture configuration during maintenance for neural progenitor cells (NPCs) influences cell fate and motility in vitro as well as in vivo. Our findings have implication for understanding different cellular characteristics of NPCs according to distinct intercellular architectures and for developing cell-based therapeutic strategies using lineage-committed NPCs

Cystamine induces AIF-mediated apoptosis through glutathione depletion

AbstractCystamine and its reduced form cysteamine showed protective effects in various models of neurodegenerative disease, including Huntington's disease and Parkinson's disease. Other lines of evidence demonstrated the cytotoxic effect of cysteamine on duodenal mucosa leading to ulcer development. However, the mechanism for cystamine cytotoxicity remains poorly understood. Here, we report a new pathway in which cystamine induces apoptosis by targeting apoptosis-inducing factor (AIF). By screening of various cell lines, we observed that cystamine and cysteamine induce cell death in a cell type-specific manner. Comparison between cystamine-sensitive and cystamine-resistant cell lines revealed that cystamine cytotoxicity is not associated with unfolded protein response, reactive oxygen species generation and transglutaminase or caspase activity; rather, it is associated with the ability of cystamine to trigger AIF nuclear translocation. In cystamine-sensitive cells, cystamine suppresses the levels of intracellular glutathione by inhibiting γ-glutamylcysteine synthetase expression that triggers AIF translocation. Conversely, glutathione supplementation completely prevents cystamine-induced AIF translocation and apoptosis. In rats, cysteamine administration induces glutathione depletion and AIF translocation leading to apoptosis of duodenal epithelium. These results indicate that AIF translocation through glutathione depletion is the molecular mechanism of cystamine toxicity, and provide important implications for cystamine in the neurodegenerative disease therapeutics as well as in the regulation of AIF-mediated cell death

Survival pattern in male breast cancer: distinct from female breast cancer

IntroductionMale breast cancer (MBC) is a rare condition, and recent research has underscored notable distinctions between MBC and breast cancer in women. This study aimed to assess and contrast the long-term survival outcomes and disease patterns of MBC patients with those of their female counterparts.MethodsWe analyzed data from 113,845 patients diagnosed with breast cancer who had undergone curative surgery from the Korean Breast Cancer Registry (KBCR) between January 1990 and August 2014 in Seoul, Korea. The five-year overall survival was analyzed according to clinicopathological characteristics.ResultsAmong 113,845 patients with breast cancer, 473 MBC cases were included. The median duration of follow-up was 72 months. The median age at diagnosis was 60 and 48 years for MBC and female breast cancer, respectively. Most male patients (92.6%) underwent total mastectomy, while 50.4% of female patients underwent breast-conserving surgery. Among MBC, 63.2% received chemotherapy, and 83.9% of hormone receptor-positive male patients received endocrine therapy. In survival analysis, MBC demonstrated distinct 5-year overall survival patterns compared with female breast cancer, according to age at diagnosis. In women with breast cancer, the younger age group (≤40 years) demonstrated worse 5-year overall survival than did the older age group (>40 years) (91.3% vs 92.7%, p <0.05). While in MBC, the younger age group (≤40 years) demonstrated better 5-year overall survival than did the older age group (>40 years) (97.4% vs 86.4%, p <0.05).DiscussionIn conclusion within this extensive cohort, we have revealed unique survival patterns in MBC that diverge from those observed in women with breast cancer. This study enhances our comprehension of MBC prognosis and can potentially shed light on unresolved questions, paving the way for future research in the realm of MBC

Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR)

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Abstract Background Neoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in patients with postmenopausal breast cancer. Preclinical and clinical studies have shown that the antidiabetic drug metformin has anti-tumor activity. This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer. Methods/Design Patients meeting the inclusion criteria and providing written informed consent will be randomized to 24 weeks of neoadjuvant treatment with letrozole (2.5 mg/day) and either metformin (2000 mg/day) or placebo. Target accrual number is 104 patients per arm. The primary endpoint will be clinical response rate, as measured by calipers. Secondary endpoints include pathologic complete response rate, breast conserving rate, change in Ki67 expression, breast density change, and toxicity profile. Molecular assays will be performed using samples obtained before treatment, at week 4, and postoperatively. Discussion This study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer. Trial registration ClinicalTrials.gov Identifier NCT0158936

Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR)

This study is being supported by grant no 04-2012-0290 from the SNUH Research fund and by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIP)(No. 2013005540). Letrozole and metformin are being supplied by the pharmaceutical company, Shin Poong Pharm. Co., Ltd.Background : Neoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in patients with postmenopausal breast cancer. Preclinical and clinical studies have shown that the antidiabetic drug metformin has anti-tumor activity. This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer. Methods/Design : Patients meeting the inclusion criteria and providing written informed consent will be randomized to 24 weeks of neoadjuvant treatment with letrozole (2.5 mg/day) and either metformin (2000 mg/day) or placebo. Target accrual number is 104 patients per arm. The primary endpoint will be clinical response rate, as measured by calipers. Secondary endpoints include pathologic complete response rate, breast conserving rate, change in Ki67 expression, breast density change, and toxicity profile. Molecular assays will be performed using samples obtained before treatment, at week 4, and postoperatively. Discussion : This study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer. Trial registration : ClinicalTrials.gov Identifier NCT01589367Peer Reviewe

Image_3_The effectiveness of a brief video-based intervention in reducing gender bias in Korea.pdf

IntroductionGender bias deepens gender disparities by fueling gender conflicts. Thus, effective interventions for gender bias are necessary. Understanding gender discrimination experienced by another gender, both emotionally and logically, may contribute to reducing gender bias in Korean society. Hence, we conducted an online experiment using Video Interventions for Diversity in Science, Technology, Engineering, and Mathematics (VIDS) to examine the effectiveness of shortened VIDS intervention through perspective taking in reducing gender bias.MethodsA sample of Korean adults aged 19–39 (n = 160, 61.8% women, 38.2% men) were recruited. In the treatment group, male participants watched VIDS videos that portrayed a woman getting gender prejudiced and female participants watched VIDS videos showing a man receiving gender biased treatment in the society. The videos presented to treatment group consisted of one narrative and one expert video from VIDS, which stimulate emotional and logical understanding of the another gender, respectively. Participants in the control group watched a control video that was irrelevant to gender bias. All participants then answered gender bias questionnaire, as well as cultural orientation questionnaire.ResultsCultural orientation as a covariance, ANCOVA (Analysis of Covariance) revealed participants in the treatment group showed significantly lower gender bias than the control group. Within the treatment group, a moderation analysis showed that logical thinking moderated the relationship between emotional immersion and decreased gender bias, meaning stimulated logical thinking from watching the videos affected how engaging emotionally to the another gender’s situation lowers gender bias.DiscussionOur findings suggest that VIDS, a video-based gender bias intervention tool, can still be effective when edited briefly. Furthermore, one’s perspective-taking strategy can be considered when trying to decrease gender bias through videos that promote perspective-taking. The findings highlight the possibility of utilizing short video intervention that enhances perspective taking on decreasing gender bias.</p

Image_4_The effectiveness of a brief video-based intervention in reducing gender bias in Korea.pdf

IntroductionGender bias deepens gender disparities by fueling gender conflicts. Thus, effective interventions for gender bias are necessary. Understanding gender discrimination experienced by another gender, both emotionally and logically, may contribute to reducing gender bias in Korean society. Hence, we conducted an online experiment using Video Interventions for Diversity in Science, Technology, Engineering, and Mathematics (VIDS) to examine the effectiveness of shortened VIDS intervention through perspective taking in reducing gender bias.MethodsA sample of Korean adults aged 19–39 (n = 160, 61.8% women, 38.2% men) were recruited. In the treatment group, male participants watched VIDS videos that portrayed a woman getting gender prejudiced and female participants watched VIDS videos showing a man receiving gender biased treatment in the society. The videos presented to treatment group consisted of one narrative and one expert video from VIDS, which stimulate emotional and logical understanding of the another gender, respectively. Participants in the control group watched a control video that was irrelevant to gender bias. All participants then answered gender bias questionnaire, as well as cultural orientation questionnaire.ResultsCultural orientation as a covariance, ANCOVA (Analysis of Covariance) revealed participants in the treatment group showed significantly lower gender bias than the control group. Within the treatment group, a moderation analysis showed that logical thinking moderated the relationship between emotional immersion and decreased gender bias, meaning stimulated logical thinking from watching the videos affected how engaging emotionally to the another gender’s situation lowers gender bias.DiscussionOur findings suggest that VIDS, a video-based gender bias intervention tool, can still be effective when edited briefly. Furthermore, one’s perspective-taking strategy can be considered when trying to decrease gender bias through videos that promote perspective-taking. The findings highlight the possibility of utilizing short video intervention that enhances perspective taking on decreasing gender bias.</p

Image_2_The effectiveness of a brief video-based intervention in reducing gender bias in Korea.pdf

IntroductionGender bias deepens gender disparities by fueling gender conflicts. Thus, effective interventions for gender bias are necessary. Understanding gender discrimination experienced by another gender, both emotionally and logically, may contribute to reducing gender bias in Korean society. Hence, we conducted an online experiment using Video Interventions for Diversity in Science, Technology, Engineering, and Mathematics (VIDS) to examine the effectiveness of shortened VIDS intervention through perspective taking in reducing gender bias.MethodsA sample of Korean adults aged 19–39 (n = 160, 61.8% women, 38.2% men) were recruited. In the treatment group, male participants watched VIDS videos that portrayed a woman getting gender prejudiced and female participants watched VIDS videos showing a man receiving gender biased treatment in the society. The videos presented to treatment group consisted of one narrative and one expert video from VIDS, which stimulate emotional and logical understanding of the another gender, respectively. Participants in the control group watched a control video that was irrelevant to gender bias. All participants then answered gender bias questionnaire, as well as cultural orientation questionnaire.ResultsCultural orientation as a covariance, ANCOVA (Analysis of Covariance) revealed participants in the treatment group showed significantly lower gender bias than the control group. Within the treatment group, a moderation analysis showed that logical thinking moderated the relationship between emotional immersion and decreased gender bias, meaning stimulated logical thinking from watching the videos affected how engaging emotionally to the another gender’s situation lowers gender bias.DiscussionOur findings suggest that VIDS, a video-based gender bias intervention tool, can still be effective when edited briefly. Furthermore, one’s perspective-taking strategy can be considered when trying to decrease gender bias through videos that promote perspective-taking. The findings highlight the possibility of utilizing short video intervention that enhances perspective taking on decreasing gender bias.</p

Image_1_The effectiveness of a brief video-based intervention in reducing gender bias in Korea.pdf

IntroductionGender bias deepens gender disparities by fueling gender conflicts. Thus, effective interventions for gender bias are necessary. Understanding gender discrimination experienced by another gender, both emotionally and logically, may contribute to reducing gender bias in Korean society. Hence, we conducted an online experiment using Video Interventions for Diversity in Science, Technology, Engineering, and Mathematics (VIDS) to examine the effectiveness of shortened VIDS intervention through perspective taking in reducing gender bias.MethodsA sample of Korean adults aged 19–39 (n = 160, 61.8% women, 38.2% men) were recruited. In the treatment group, male participants watched VIDS videos that portrayed a woman getting gender prejudiced and female participants watched VIDS videos showing a man receiving gender biased treatment in the society. The videos presented to treatment group consisted of one narrative and one expert video from VIDS, which stimulate emotional and logical understanding of the another gender, respectively. Participants in the control group watched a control video that was irrelevant to gender bias. All participants then answered gender bias questionnaire, as well as cultural orientation questionnaire.ResultsCultural orientation as a covariance, ANCOVA (Analysis of Covariance) revealed participants in the treatment group showed significantly lower gender bias than the control group. Within the treatment group, a moderation analysis showed that logical thinking moderated the relationship between emotional immersion and decreased gender bias, meaning stimulated logical thinking from watching the videos affected how engaging emotionally to the another gender’s situation lowers gender bias.DiscussionOur findings suggest that VIDS, a video-based gender bias intervention tool, can still be effective when edited briefly. Furthermore, one’s perspective-taking strategy can be considered when trying to decrease gender bias through videos that promote perspective-taking. The findings highlight the possibility of utilizing short video intervention that enhances perspective taking on decreasing gender bias.</p