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1.
Nat Commun ; 15(1): 4114, 2024 May 15.
Article En | MEDLINE | ID: mdl-38750057

Cellular sensitivity to ferroptosis is primarily regulated by mechanisms mediating lipid hydroperoxide detoxification. We show that inositol-requiring enzyme 1 (IRE1α), an endoplasmic reticulum (ER) resident protein critical for the unfolded protein response (UPR), also determines cellular sensitivity to ferroptosis. Cancer and normal cells depleted of IRE1α gain resistance to ferroptosis, while enhanced IRE1α expression promotes sensitivity to ferroptosis. Mechanistically, IRE1α's endoribonuclease activity cleaves and down-regulates the mRNA of key glutathione biosynthesis regulators glutamate-cysteine ligase catalytic subunit (GCLC) and solute carrier family 7 member 11 (SLC7A11). This activity of IRE1α is independent of its role in regulating the UPR and is evolutionarily conserved. Genetic deficiency and pharmacological inhibition of IRE1α have similar effects in inhibiting ferroptosis and reducing renal ischemia-reperfusion injury in mice. Our findings reveal a previously unidentified role of IRE1α to regulate ferroptosis and suggests inhibition of IRE1α as a promising therapeutic strategy to mitigate ferroptosis-associated pathological conditions.


Amino Acid Transport System y+ , Endoribonucleases , Ferroptosis , Glutathione , Protein Serine-Threonine Kinases , Ferroptosis/genetics , Endoribonucleases/metabolism , Endoribonucleases/genetics , Animals , Humans , Protein Serine-Threonine Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Mice , Glutathione/metabolism , Amino Acid Transport System y+/metabolism , Amino Acid Transport System y+/genetics , Glutamate-Cysteine Ligase/metabolism , Glutamate-Cysteine Ligase/genetics , Unfolded Protein Response , Reperfusion Injury/metabolism , Reperfusion Injury/genetics , Cell Line, Tumor , Mice, Inbred C57BL , Male , Mice, Knockout
2.
J Clin Invest ; 134(8)2024 Apr 15.
Article En | MEDLINE | ID: mdl-38618953

N6-Methyladenosine (m6A), a prevalent posttranscriptional modification, plays an important role in cancer progression. Clear cell renal cell carcinoma (ccRCC) is chiefly associated with the loss of the von Hippel-Lindau (VHL) gene, encoding a component of the E3 ubiquitin ligase complex. In this issue of the JCI, Zhang and colleagues unveiled a function of VHL beyond its canonical role as an E3 ubiquitin ligase in regulating hypoxia-inducible factors (HIFs). It also governed m6A modification by orchestrating the assembly of m6A writer proteins METTL3 and METTL14, thereby stabilizing PIK3R3 mRNA. Mechanistically, PIK3R3 contributed to p85 ubiquitination, which restrained PI3K/AKT signaling and consequently impeded ccRCC growth in cell and mouse models. This discovery provides potential treatment targets in VHL-deficient ccRCCs.


Adenine , Carcinoma, Renal Cell , Kidney Neoplasms , Animals , Mice , Carcinoma, Renal Cell/genetics , Kidney Neoplasms/genetics , Phosphatidylinositol 3-Kinases/genetics , RNA Stability , Ubiquitin-Protein Ligases , Humans
3.
Int J Transgend Health ; 25(2): 283-294, 2024.
Article En | MEDLINE | ID: mdl-38681498

Introduction: Using Asia's first nationwide cohort dataset, this study aimed to assess the prevalence of anti-transgender discrimination and healthcare avoidance and delay (HAD) and examine their associations among transgender and gender diverse (TGD) adults in South Korea. Methods: We analyzed a two-wave (2020-2021) longitudinal dataset of 190 Korean TGD adults. Anti-transgender discrimination were classified accordingly: experienced at (1) neither wave, (2) baseline (2020) only, (3) follow-up (2021) only, and (4) both waves. We also asked about HAD in the past 12 months at follow-up for both transition-related and non-transition-related healthcare services. Multivariate modified Poisson regression was used to examine the associations between anti-transgender discrimination and HAD. Results: Of 190 participants, 102 (53.7%) experienced anti-transgender discrimination at both waves, and 130 (68.4%) reported HAD at follow-up. Compared to those without any experiences of anti-transgender discrimination, those who experienced it in both waves had a 1.78-times (95% CI: 1.21-2.63) higher prevalence of non-transition-related HAD, but not among those who experienced it in either wave. In contrast, anti-transgender discrimination was not associated with transition-related HAD. Conclusion: In order to enhance healthcare access for transgender and gender diverse (TGD) individuals, it is necessary to implement interventions, such as anti-discrimination laws, that protect them from discrimination.

4.
Cancer Discov ; 2024 Mar 28.
Article En | MEDLINE | ID: mdl-38552003

Resistance to poly (ADP-ribose) polymerase inhibitors (PARPi) limits the therapeutic efficacy of PARP inhibition in treating breast cancer susceptibility gene 1 (BRCA1)-deficient cancers. Here we reveal that BRCA1 has a dual role in regulating ferroptosis. BRCA1 promotes the transcription of voltage-dependent anion channel 3 (VDAC3) and glutathione peroxidase 4 (GPX4); consequently, BRCA1 deficiency promotes cellular resistance to erastin-induced ferroptosis but sensitizes cancer cells to ferroptosis induced by GPX4 inhibitors (GPX4i). In addition, nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and defective GPX4 induction unleash potent ferroptosis in BRCA1-deficient cancer cells upon PARPi and GPX4i co-treatment. Finally, we show that xenograft tumors derived from BRCA1-mutant breast cancer patients with PARPi resistance exhibit decreased GPX4 expression and high sensitivity to PARP and GPX4 co-inhibition. Our results show that BRCA1 deficiency induces a ferroptosis vulnerability to PARP and GPX4 co-inhibition and inform a therapeutic strategy for overcoming PARPi resistance in BRCA1-deficient cancers.

5.
Healthcare (Basel) ; 12(5)2024 Mar 01.
Article En | MEDLINE | ID: mdl-38470687

The aim of this study is to enhance comprehension of the different types and features of dementia, including their symptoms, diagnosis and medical treatment, and to propose various evidence-based exercise interventions and their clinical applications tailored to each specific type of dementia. The theoretical review includes the analysis of publications in the scientific databases PubMed/Medline, Ebsco, Scielo, and Google. A total of 177 articles were found, of which 84 were studied in depth. With the prevalence of all forms of dementia projected to increase from 57.4 million in 2019 to 152.8 million in 2050, personalized treatment strategies are needed. This review discusses various forms of dementia, including their pathologies, diagnostic criteria, and prevalence rates. The importance of accurate diagnosis and tailored care is emphasized, as well as the effectiveness of physical exercise in improving cognitive function in dementia patients. For Alzheimer's, a combination of drug therapies and exercises is recommended to enhance cerebral blood flow and neurotransmitter activity. To improve cognitive and motor functions in Lewy body dementia, a combination of pharmacological and physical therapies is recommended. For managing frontotemporal dementia, a mix of medication and exercises aimed at emotion regulation, including aerobic exercises, and a unified protocol, is suggested. For mild cognitive impairment, aerobic and functional exercises are important in delaying cognitive decline and enhancing cognitive performance. In conclusion, individualized care and treatment plans tailored to the specific characteristics of each disease type can improve the quality of life for individuals with this condition and effectively manage this growing global health issue.

6.
Protein Cell ; 2024 Mar 02.
Article En | MEDLINE | ID: mdl-38430542

Ferroptosis has been recognized as a unique cell death modality driven by excessive lipid peroxidation and unbalanced cellular metabolism. In this study, we established a protein interaction landscape for ferroptosis pathways through proteomic analyses, and identified choline/ethanolamine phosphotransferase 1 (CEPT1) as a lysophosphatidylcholine acyltransferase 3 (LPCAT3)-interacting protein that regulates LPCAT3 protein stability. In contrast to its known role in promoting phospholipid synthesis, we showed that CEPT1 suppresses ferroptosis potentially by interacting with phospholipases and breaking down certain pro-ferroptotic polyunsaturated fatty acid (PUFA)-containing phospholipids. Together, our study reveals a previously unrecognized role of CEPT1 in suppressing ferroptosis.

7.
J Pediatr Nurs ; 77: 35-44, 2024 Mar 12.
Article En | MEDLINE | ID: mdl-38479061

PURPOSE: This study aimed to develop and evaluate the effectiveness of a healthy lifestyle program based on a mobile serious game (HLP-MSG) to enhance the lifestyles of childhood cancer survivors (CCSs). METHODS: This program proceeded in two stages: development and evaluation, using a non-synchronized design with a quasi-randomized trial. The participants were CCSs aged 6-13 years whose treatment was terminated at least 12 months prior. Data were collected at baseline, and post-intervention, with a follow-up after four weeks using the Child Healthy Lifestyle Profile (CHLP). The experimental (n = 26) and control groups (n = 25) were compared. Data were analyzed using descriptive statistics, chi-squared tests, t-tests, and repeated-measures ANOVA. RESULTS: The HLP-MSG promoted a healthy lifestyle by solving 26 quests, including seven sub-elements (nutrition, exercise, hygiene, interpersonal relationships, stress management, meaning of life, and health responsibility). This study revealed significant differences in the interaction between measurement time and group assignment in the CHLP (p = .006) and physical activity (p = .013), one of the seven sub-dimensions. CONCLUSIONS: A healthy lifestyle program based on a mobile serious game is a feasible health education modality to enhance the physical, psychological, social, and spiritual health of CCSs. IMPLICATIONS TO PRACTICE: The findings add to scientific evidence on a mobile serious game for health education among CCSs. The HLP-MSG provides an evolutionary educational modality that can be delivered non-face-to-face to promote CCSs' continuous healthy behavior maintenance. Moreover, the HLP-MSG is adolescent-friendly and can be utilized as a healthcare tool for parents and children to cooperate.

8.
Mol Cancer ; 23(1): 45, 2024 02 29.
Article En | MEDLINE | ID: mdl-38424542

BACKGROUND: In the myeloid compartment of the tumor microenvironment, CD244 signaling has been implicated in immunosuppressive phenotype of monocytes. However, the precise molecular mechanism and contribution of CD244 to tumor immunity in monocytes/macrophages remains elusive due to the co-existing lymphoid cells expressing CD244. METHODS: To directly assess the role of CD244 in tumor-associated macrophages, monocyte-lineage-specific CD244-deficient mice were generated using cre-lox recombination and challenged with B16F10 melanoma. The phenotype and function of tumor-infiltrating macrophages along with antigen-specific CD8 T cells were analyzed by flow cytometry and single cell RNA sequencing data analysis, and the molecular mechanism underlying anti-tumorigenic macrophage differentiation, antigen presentation, phagocytosis was investigated ex vivo. Finally, the clinical feasibility of CD244-negative monocytes as a therapeutic modality in melanoma was confirmed by adoptive transfer experiments. RESULTS: CD244fl/flLysMcre mice demonstrated a significant reduction in tumor volume (61% relative to that of the CD244fl/fl control group) 14 days after tumor implantation. Within tumor mass, CD244fl/flLysMcre mice also showed higher percentages of Ly6Clow macrophages, along with elevated gp100+IFN-γ+ CD8 T cells. Flow cytometry and RNA sequencing data demonstrated that ER stress resulted in increased CD244 expression on monocytes. This, in turn, impeded the generation of anti-tumorigenic Ly6Clow macrophages, phagocytosis and MHC-I antigen presentation by suppressing autophagy pathways. Combining anti-PD-L1 antibody with CD244-/- bone marrow-derived macrophages markedly improved tumor rejection compared to the anti-PD-L1 antibody alone or in combination with wild-type macrophages. Consistent with the murine data, transcriptome analysis of human melanoma tissue single-cell RNA-sequencing dataset revealed close association between CD244 and the inhibition of macrophage maturation and function. Furthermore, the presence of CD244-negative monocytes/macrophages significantly increased patient survival in primary and metastatic tumors. CONCLUSION: Our study highlights the novel role of CD244 on monocytes/macrophages in restraining anti-tumorigenic macrophage generation and tumor antigen-specific T cell response in melanoma. Importantly, our findings suggest that CD244-deficient macrophages could potentially be used as a therapeutic agent in combination with immune checkpoint inhibitors. Furthermore, CD244 expression in monocyte-lineage cells serve as a prognostic marker in cancer patients.


Melanoma , Monocytes , Humans , Animals , Mice , Monocytes/metabolism , Melanoma/drug therapy , Melanoma/genetics , Melanoma/metabolism , B7-H1 Antigen/genetics , B7-H1 Antigen/metabolism , Macrophages/metabolism , CD8-Positive T-Lymphocytes , Carcinogenesis/metabolism , Tumor Microenvironment , Signaling Lymphocytic Activation Molecule Family/metabolism
9.
Nat Commun ; 15(1): 79, 2024 01 02.
Article En | MEDLINE | ID: mdl-38167301

How cells coordinate cell cycling with cell survival and death remains incompletely understood. Here, we show that cell cycle arrest has a potent suppressive effect on ferroptosis, a form of regulated cell death induced by overwhelming lipid peroxidation at cellular membranes. Mechanistically, cell cycle arrest induces diacylglycerol acyltransferase (DGAT)-dependent lipid droplet formation to sequester excessive polyunsaturated fatty acids (PUFAs) that accumulate in arrested cells in triacylglycerols (TAGs), resulting in ferroptosis suppression. Consequently, DGAT inhibition orchestrates a reshuffling of PUFAs from TAGs to phospholipids and re-sensitizes arrested cells to ferroptosis. We show that some slow-cycling antimitotic drug-resistant cancer cells, such as 5-fluorouracil-resistant cells, have accumulation of lipid droplets and that combined treatment with ferroptosis inducers and DGAT inhibitors effectively suppresses the growth of 5-fluorouracil-resistant tumors by inducing ferroptosis. Together, these results reveal a role for cell cycle arrest in driving ferroptosis resistance and suggest a ferroptosis-inducing therapeutic strategy to target slow-cycling therapy-resistant cancers.


Ferroptosis , Neoplasms , Humans , Lipid Droplets/metabolism , Fatty Acids, Unsaturated/metabolism , Lipid Peroxidation , Triglycerides/metabolism , Cell Cycle Checkpoints , Neoplasms/metabolism , Diacylglycerol O-Acyltransferase/metabolism , Fluorouracil/pharmacology , Fluorouracil/therapeutic use
10.
LGBT Health ; 11(2): 122-130, 2024.
Article En | MEDLINE | ID: mdl-37831924

Purpose: In fear of discrimination or unwanted disclosure of their transgender identity, transgender and nonbinary (TGNB) people may commonly avoid daily activities. We assessed the prevalence of situational avoidance among TGNB people and examined its associations with mental health outcomes. Methods: We analyzed data from a longitudinal survey conducted at baseline (2020) and follow-up (2021) among 268 TGNB people in South Korea. Situational avoidance due to transgender identity within the past 12 months was assessed based on 12 kinds of daily activities (e.g., public bathroom use, job applications, and hospital visits). Past-week depressive symptoms and past 2-week anxiety symptoms were measured with the Center for Epidemiologic Studies-Depression Scale and General Anxiety Disorder Scale, respectively. Results: Of 268 participants, 135 (50.4%) have ever avoided daily activities. The most frequently reported situational avoidance was public bathroom use (32.1%), followed by job applications (24.3%) and hospital visits (12.3%). After adjusting for confounders including baseline depressive symptoms and experience of anti-transgender discrimination, participants with any situational avoidance experience were 1.30 times (95% confidence intervals [CI] = 1.01-1.69) more likely to have anxiety symptoms compared with those without situational avoidance experience. In particular, participants who avoided three or more kinds of daily activities were 1.40 times (95% CI = 1.02-1.93) more likely to have anxiety symptoms than those without any experience of situational avoidance. No association was observed with depressive symptoms. Conclusion: Multilateral interventions including anti-discrimination law enactment are necessary to reduce transphobia and provide support for TGNB people in Korea, thus reducing their fear of participating in daily activities and promoting their mental well-being.


Anxiety Disorders , Transgender Persons , Adult , Humans , Mental Health , Cohort Studies , Republic of Korea/epidemiology
11.
Proc Natl Acad Sci U S A ; 120(49): e2308292120, 2023 Dec 05.
Article En | MEDLINE | ID: mdl-38032932

RNA-binding motif protein 10 (RBM10) is a frequently mutated tumor suppressor in lung adenocarcinoma (LUAD). Yet, it remains unknown whether cancer-derived mutant RBM10 compromises its tumor suppression function and, if so, the molecular insight of the underlying mechanisms. Here, we show that wild-type RBM10 suppresses lung cancer cell growth and proliferation by inactivating c-Myc that is essential for cancer cell survival. RBM10 directly binds to c-Myc and promotes c-Myc's ubiquitin-dependent degradation, while RBM10 knockdown leads to the induction of c-Myc level and activity. This negative action on c-Myc is further boosted by ribosomal proteins (RPs) uL18 (RPL5) and uL5 (RPL11) via their direct binding to RBM10. Cancer-derived mutant RBM10-I316F fails to bind to uL18 and uL5 and to inactivate c-Myc, thus incapable of suppressing tumorigenesis. Our findings uncover RBM10 as a pivotal c-Myc repressor by cooperating with uL18 and uL5 in lung cancer cells, as its failure to do so upon mutation favors tumorigenesis.


Lung Neoplasms , Proto-Oncogene Proteins c-myc , RNA-Binding Proteins , Ribosomal Proteins , Humans , Carcinogenesis , Cell Proliferation/genetics , Cell Transformation, Neoplastic , Lung Neoplasms/genetics , Proto-Oncogene Proteins c-myc/genetics , Proto-Oncogene Proteins c-myc/metabolism , Ribosomal Proteins/genetics , Ribosomal Proteins/metabolism , RNA-Binding Motifs , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism
12.
Article En | MEDLINE | ID: mdl-37632566

PURPOSE: Recently, there has been an increase in awareness of social stigma and mental health issues experienced by transgender individuals in South Korea. To provide quantitative evidence, we conducted a nationwide cohort study of transgender adults, first of its kind in Asia. The aim of the study is to assess the prevalence of depressive and anxiety symptoms and examine their associations with discrimination experiences among transgender adults. METHODS: We conducted a two-wave longitudinal survey of 269 Korean transgender adults, where the baseline was collected in October 2020 and the follow-up in October 2021. Experiences of discrimination in the past 12 months at follow-up were categorized accordingly: those who experienced (1) none, (2) only anti-transgender discrimination, (3) only other types of discrimination, and (4) both anti-transgender and other types of discrimination. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression scale at both waves and anxiety symptoms were measured using the Generalized Anxiety Disorder 7 only at follow-up. We used modified Poisson regression to examine the association between experiences of discrimination and mental health outcomes at follow-up and adjusted for sociodemographic characteristics and baseline depressive symptoms. RESULTS: A total of 63.9% had depressive symptoms and 47.2% had anxiety symptoms. Participants who experienced both anti-transgender and other types of discrimination had 1.38-times (95% CI 1.06-1.81) and 1.77-times (95% CI 1.16-2.70) higher prevalence of depressive and anxiety symptoms, respectively, compared to those without any experiences of discrimination. CONCLUSIONS: Interventions to lessen discrimination towards transgender individuals are needed for the promotion of mental health among transgender individuals.

13.
Int J Transgend Health ; 24(3): 334-345, 2023.
Article En | MEDLINE | ID: mdl-37519917

Introduction: COVID-19 has disproportionately impacted marginalized groups, including transgender populations, reproducing and exacerbating inequalities and vulnerabilities that existed in those groups prior to the pandemic. This study aimed to assess the prevalence of transgender-specific COVID-19-related stressors and their association with depressive symptoms among South Korean transgender adults. Methods: We conducted a nationwide cross-sectional study of 564 South Korean transgender adults (trans women, trans men, and nonbinary people) from October 7 to October 31, 2020. We measured four transgender-specific COVID-19-related stressors as follows: (A) had difficulty receiving gender-affirming healthcare due to economic hardship related to COVID-19, (B) had difficulty receiving gender-affirming healthcare due to limited access to hospitals under the COVID-19 situation, (C) had difficulty purchasing a public face mask due to gender information on an identification card, and (D) avoided getting a COVID-19 test in fear of unfair treatment and dirty looks due to gender identity, despite having COVID-19 symptoms. Past-week depressive symptoms were assessed using the Center for Epidemiologic Studies-Depression Scale. Results: Of the total participants, 30.7% experienced any of the four transgender-specific COVID-19-related stressors, and 70.2% were classified as having depressive symptoms during the past week. We found statistically significant associations with depressive symptoms among participants who reported that they had difficulty receiving gender-affirming healthcare due to either economic hardship (adjusted prevalence ratio [aPR] = 1.20, 95% Confidence Interval [CI] = 1.05-1.37) or limited access to hospitals (aPR = 1.15, 95% CI = 1.00-1.32), respectively. Furthermore, those who had two or more of the four transgender-specific COVID-19-related stressors were 1.21 times (95% CI = 1.05-1.40) more likely to report depressive symptoms, compared to those who did not report any stressor. Conclusion: Transgender-specific COVID-19-related stressors may negatively influence depressive symptoms among South Korean transgender adults. Given these findings, transgender-inclusive interventions should be implemented at the policy level during the COVID-19 pandemic in South Korea.

14.
JAMA Pediatr ; 2023 Jul 31.
Article En | MEDLINE | ID: mdl-37523204

This cross-sectional study analyzes data from 2 statewide school surveys to document the experiences of sexual and gender minoritized Asian American, Native Hawaiian, and Pacific Islander students in grades 9 through 12 who reported bullying related to their identity.

15.
Transgend Health ; 8(3): 273-281, 2023 Jun.
Article En | MEDLINE | ID: mdl-37342483

Purpose: Gender identity change efforts (GICEs), sometimes referred to as "conversion therapy," are considered pseudoscientific and unethical practices that are not supported by the existing scientific literature. However, a substantial portion of transgender people face such practices during their lives. We assessed lifetime exposure to GICEs and its associations with mental health indicators among transgender adults in South Korea. Methods: We analyzed a nationwide cross-sectional survey of 566 Korean transgender adults conducted in October 2020. Lifetime exposure to GICEs was classified as follows: "never had GICE-related experiences," "received a referral, but did not undergo GICEs," and "undergone GICEs." We assessed mental health indicators, including past-week depressive symptoms; medical diagnosis or treatment of depression and panic disorder; and past 12-month suicidal ideation, suicide attempts, and self-harm. Results: Of the total participants, 12.2% had "received a referral, but did not undergo GICEs," and 11.5% had "undergone GICEs." Compared with those who had "never had GICE-related experiences," participants who had "undergone GICEs" showed significantly higher prevalence of depression (adjusted prevalence ratio [aPR]=1.34, 95% confidence interval [CI]=1.11-1.61), panic disorder (aPR=2.52, 95% CI=1.75-3.64), and suicide attempts (aPR=1.73, 95% CI=1.10-2.72). However, we did not find significant associations between having "received a referral, but did not undergo GICEs" and mental health indicators. Conclusion: Given our findings suggest that lifetime exposure to GICEs may harm transgender adults' mental health, legal restrictions should be imposed to ban GICEs in South Korea.

16.
Nano Converg ; 10(1): 27, 2023 Jun 16.
Article En | MEDLINE | ID: mdl-37326774

Organic-inorganic hybrid perovskites have revolutionized solar cell research owing to their excellent material properties. Most previous research has been done on Pb-based perovskites. Recently, efforts to discover a Pb-free or Pb-less perovskite material with an ideal bandgap ranging 1.1-1.3 eV have led researchers to investigate Sn-Pb mixed perovskites. Sn-Pb mixed perovskites have a bandgap of ~ 1.25 eV, which is suitable for high-efficiency single-junction and perovskite/perovskite tandem solar cells. Moreover, the Pb content of Sn-Pb mixed perovskites is 50-60% lower than that of Pb-based perovskites, partially mitigating the Pb toxicity issue. However, incorporating Sn2+ into the crystal structure also causes various drawbacks, such as inhomogeneous thin film morphologies, easy oxidation of Sn2+, and more vulnerable surface properties. Researchers have made substantial progress in addressing these challenges through improvements in compositional design, structural optimization, precursor design, and surface treatments. In this review, we provide a comprehensive overview of the progress in Sn-Pb mixed perovskite solar cells. Furthermore, we analyze the key variables and trends as well as provide an outlook for future directions in the research on Sn-Pb mixed perovskites.

17.
J Mol Cell Biol ; 15(6)2023 Nov 27.
Article En | MEDLINE | ID: mdl-37263799

Coiled-coil domain containing 3 (CCDC3, also called Favine) is a highly conserved protein initially identified as a protein secreted from adipocytes and endothelial cells in the vascular system with endocrine-like functions. Recently, CCDC3 was also found to function as a nuclear tumor suppressor in breast cancers. Although it is still understudied, CCDC3, since its discovery, has been shown to play multiple roles in lipid metabolism, fatty liver, abdominal obesity, anti-inflammation, atherosclerosis, and cancer. This essay is thus composed to offer an overview of these extracellular endocrine-like and intracellular (nuclear) functions of CCDC3. We also discuss the possible underlying cellular and molecular mechanisms of CCDC3, the implications for clinical translation, and the remaining puzzles about this special molecule.


Fatty Liver , Neoplasms , Humans , Endothelial Cells/metabolism , Proteins/genetics , Genes, Tumor Suppressor
18.
Trends Cancer ; 9(7): 524-525, 2023 07.
Article En | MEDLINE | ID: mdl-37173186

Resistance to FLT3 inhibition is a prevalent challenge in managing FLT3-mutant acute myeloid leukemia (AML). A recent study by Sabatier et al. discovered ferroptosis vulnerability in FLT3-mutant AML and they propose a promising therapeutic approach of combining FLT3 inhibitors with ferroptosis inducers for treating this type of cancer.


Ferroptosis , Leukemia, Myeloid, Acute , Humans , Ferroptosis/genetics , Mutation , Protein Kinase Inhibitors/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , fms-Like Tyrosine Kinase 3/genetics , fms-Like Tyrosine Kinase 3/therapeutic use
19.
Nanomaterials (Basel) ; 13(2)2023 Jan 07.
Article En | MEDLINE | ID: mdl-36678013

Activated carbon (AC) is used in commercial electric double-layer capacitors (EDLC) as electrode active material owing to its favorable properties. However, oxygen functional groups (OFGs) present in AC reduce the lifespan of EDLCs. Thus, we investigated the correlation between the OFGs in AC and their electrochemical characteristics. Samples were prepared by heat-treating commercial AC at 300 °C-900 °C for 1 h under two gas atmospheres (N2 and 4% H2/N2 mixed gas). The textural properties were studied, and the reduction characteristics of AC under Ar and H2/Ar mixed gas atmospheres were investigated. Additionally, changes in the OFGs with respect to the heat-treatment conditions were examined via X-ray photoelectron spectroscopy. The specific surface areas of AC-N and AC-H were 2220-2040 and 2220-2090 m2/g, respectively. Importantly, the samples treated in hydrogen gas exhibited a higher yield than those treated in nitrogen while maintaining their pore characteristics. Additionally, the electrochemical performance of the AC was significantly enhanced after the reduction process; the specific capacitance increased from 62.1 F/g to 81.6 F/g (at 0.1 A/g). Thus, heat treatment in hydrogen gas improves the electrochemical performance of EDLCs without destroying the pore characteristics of AC.

20.
AIDS Care ; 35(5): 672-677, 2023 05.
Article En | MEDLINE | ID: mdl-35642248

Limited research has been conducted on factors contributing to HIV testing among sexual minority populations in South Korea (hereafter, Korea), where stigma against homosexuality and HIV/AIDS is pervasive. We used a nationwide cross-sectional survey of 907 Korean cisgender gay and bisexual (GB) men who were HIV-negative or HIV-unknown in 2016. Regarding internalized homophobia (IHP), participants were categorized into tertiles (low, moderate, and high). Past 12-month HIV testing was assessed via a single yes/no question. Using a modified Poisson regression model, we examined the association between IHP and HIV testing among cisgender GB men in Korea. The overall prevalence of obtaining an HIV test was 41.8% among Korean cisgender GB men. We also found a statistically significant association between IHP and past 12-month HIV testing in this population. Specifically, participants with low IHP had a higher prevalence of HIV testing (adjusted PR = 1.37, 95% CI = 1.14-1.65) compared to those with high IHP. Given these findings, more efforts are needed in Korea to enhance GB men's access to HIV testing, such as improving social circumstances to lower IHP of GB men and creating an environment that enables and facilitates GB men to receive HIV testing without stigma against their sexual identity.


Acquired Immunodeficiency Syndrome , HIV Infections , Sexual and Gender Minorities , Male , Humans , Homophobia , Homosexuality, Male , Cross-Sectional Studies , HIV Infections/epidemiology , Bisexuality , Social Stigma , HIV Testing
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