We have previously shown that 2,4,3',5'-tetramethoxystilbene (TMS), a trans-stilbene analogue, induces apoptosis in human cancer cells. However, the detailed mechanisms of mitochondria-dependent apoptosis induced by TMS are not fully understood. In the present study, the possible roles of annexin A5 in TMS-mediated apoptosis were investigated in MCF7 human breast cancer cells. Quantitative real-time PCR analysis and Western blot analysis showed that the expression of annexin A5 was strongly increased in TMS-treated cells. TMS caused a strong translocation of annexin A5 from cytosol into mitochondria. Confocal laser scanning microscopic analysis clearly showed that TMS induced translocation of annexin A5 into mitochondria. TMS increased the expression and oligomerization of voltage-dependent anion channel (VDAC) 1, which may promote mitochondria-dependent apoptosis through disruption of mitochondrial membrane potential. When cells were treated with TMS, the levels of Bax, and Bak as well as annexin A5 were strongly enhanced. Moreover, we found that the cytosolic release of apoptogenic factors such as cytochrome c, or apoptosis-inducing factor (AIF) in mitochondria was markedly increased. Annexin A5 depletion by siRNA led to decreased proapoptotic factors such as Bax , Bak, and annexin A5. Taken together, our results indicate that annexin A5 may play an important role in TMS-mediated mitochondrial apoptosis through the regulation of proapoptotic proteins and VDAC1 expression.
Annexin A5* ; Apoptosis Inducing Factor ; Apoptosis* ; Blotting, Western ; Breast Neoplasms* ; Cytochromes c ; Cytosol ; Humans ; Membrane Potential, Mitochondrial ; Mitochondria ; Real-Time Polymerase Chain Reaction ; RNA, Small Interfering

Anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (anti-HMGCR) antibody related immune-mediated necrotizing myopathy (IMNM) are usually associated with statin use. The disease has features of persistent muscle weakness and creatine kinase (CK) elevation after statin discontinuation. This report describes a 65-year-old female taking atorvastatin, presenting with both proximal lower extremity weakness. IMNM feature were detected on muscle biopsy and high anti-HMGCR autoantibody titer on enzyme-linked immunosorbent assay (ELISA). This patient was treated with corticosteroid. Muscle weakness and CK are improved after immunosuppressive therapy.

Steroid sulfatase (STS) is responsible for the hydrolysis of aryl and alkyl steroid sulfates and has a pivotal role in regulating the formation of biologically active estrogens. STS may be considered a new promising drug target for treating estrogen-mediated carcinogenesis. However, the molecular mechanism of STS expression is not well-known. To investigate whether tumor necrosis factor (TNF)-alpha is able to regulate gene transcription of STS, we studied the effect of TNF-alpha on STS expression in PC-3 human prostate cancer cells. RT-PCR and Western blot analysis showed that TNF-alpha significantly induced the expression of STS mRNA and protein in a concentration- and time-dependent manner. Treatment with TNF-alpha resulted in a strong increase in the phosphorylation of Akt on Ser-473 and when cells were treated with phosphatidylinositol (PI) 3-kinase inhibitors such as LY294002 or wortmannin, or Akt inhibitor (Akt inhibitor IV), induction of STS mRNA expression by TNF-alpha was significantly prevented. Moreover, activation of Akt1 by expressing the constitutively active form of Akt1 increased STS expression whereas dominant-negative Akt suppressed TNF-alpha-mediated STS induction. We also found that TNF-alpha is able to increase STS mRNA expression in other human cancer cells such as LNCaP, MDA-MB-231, and MCF-7 as well as PC-3 cells. Taken together, our results strongly suggest that PI 3-kinase/Akt activation mediates induction of human STS gene expression by TNF-alpha in human cancer cells.
Blotting, Western ; Fluorescent Antibody Technique ; Humans ; Male ; Phosphatidylinositol 3-Kinase/genetics/*metabolism ; Phosphorylation/drug effects ; Prostatic Neoplasms/genetics/*metabolism ; Proto-Oncogene Proteins c-akt/genetics/*metabolism ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Recombinant Proteins/genetics/isolation & purification/metabolism ; Signal Transduction ; Steryl-Sulfatase/genetics/*metabolism ; Tumor Cells, Cultured ; Tumor Necrosis Factor-alpha/*pharmacology

BACKGROUND: Many studies have reported that adolescents living with single parent have a high risk of obesity. However, those studies did not explore the implication of the gender of single parent living with adolescents. This study investigated the differences in obesity rates according to status of co-residence with their parents in Korean adolescents. The family living with single parent was classified into the family living with single father and the family living with single mother. METHODS: This cross-sectional study involved 59,602 adolescents who participated in the 2017 Korea Youth Risk Behavior Web-based Survey. The data on height, weight, status of co-residence with parents, and the other variables were obtained through online questionnaires. RESULTS: In male adolescents, the family living with single mother was related to a high proportion of obesity (odds ratio [OR] 1.24, 95% confidence interval [CI] 1.09–1.40) and overweight (OR 1.17, 95% CI 1.03–1.34). However, in female adolescents, the family living with single father was related to a high proportion of obesity (OR 1.49, 95% CI 1.23–1.82). In addition, female adolescents living with neither parent were more likely to be obese (OR 1.47, 95% CI 1.13–1.91) and overweight (OR 1.31, 95% CI 1.00–1.70). CONCLUSIONS: This study showed a risk of obesity in adolescents living with single parent differs according to the gender of single parent living with adolescents. Not adolescents living with a same-gender parent, but those living with an opposite-gender parent have a high risk of obesity.
Adolescent ; Cross-Sectional Studies ; Fathers ; Humans ; Korea ; Mothers ; Obesity ; Overweight ; Parents ; Risk-Taking ; Single Parent ; Single-Parent Family

BACKGROUND: Many studies have reported that adolescents living with single parent have a high risk of obesity. However, those studies did not explore the implication of the gender of single parent living with adolescents. This study investigated the differences in obesity rates according to status of co-residence with their parents in Korean adolescents. The family living with single parent was classified into the family living with single father and the family living with single mother. METHODS: This cross-sectional study involved 59,602 adolescents who participated in the 2017 Korea Youth Risk Behavior Web-based Survey. The data on height, weight, status of co-residence with parents, and the other variables were obtained through online questionnaires. RESULTS: In male adolescents, the family living with single mother was related to a high proportion of obesity (odds ratio [OR] 1.24, 95% confidence interval [CI] 1.09–1.40) and overweight (OR 1.17, 95% CI 1.03–1.34). However, in female adolescents, the family living with single father was related to a high proportion of obesity (OR 1.49, 95% CI 1.23–1.82). In addition, female adolescents living with neither parent were more likely to be obese (OR 1.47, 95% CI 1.13–1.91) and overweight (OR 1.31, 95% CI 1.00–1.70). CONCLUSIONS This study showed a risk of obesity in adolescents living with single parent differs according to the gender of single parent living with adolescents. Not adolescents living with a same-gender parent, but those living with an opposite-gender parent have a high risk of obesity.

Pruritus (itching) is classically defined as an unpleasant cutaneous sensation that leads to scratching behavior. Although the scientific criteria of classification for pruritic diseases are not clear, it can be divided as acute or chronic by duration of symptoms. In this study, we investigated whether skin injury caused by chemical (contact hypersensitivity, CHS) or physical (skin-scratching stimulation, SSS) stimuli causes initial pruritus and analyzed gene expression profiles systemically to determine how changes in skin gene expression in the affected area are related to itching. In both CHS and SSS, we ranked the Gene Ontology Biological Process terms that are generally associated with changes. The factors associated with upregulation were keratinization, inflammatory response and neutrophil chemotaxis. The Kyoto Encyclopedia of Genes and Genomes pathway shows the difference of immune system, cell growth and death, signaling molecules and interactions, and signal transduction pathways. Il1a , Il1b and Il22 were upregulated in the CHS, and Tnf, Tnfrsf1b, Il1b, Il1r1 and Il6 were upregulated in the SSS. Trpc1 channel genes were observed in representative itching-related candidate genes. By comparing and analyzing RNA-sequencing data obtained from the skin tissue of each animal model in these characteristic stages, it is possible to find useful diagnostic markers for the treatment of itching, to diagnose itching causes and to apply customized treatment.
Animals ; Biological Processes ; Chemotaxis ; Classification ; Cytokines ; Dermatitis, Contact* ; Gene Expression ; Gene Ontology ; Genome ; Hypersensitivity ; Immune System ; Interleukin-6 ; Mice* ; Models, Animal ; Neutrophils ; Pruritus* ; RNA* ; Sensation ; Sequence Analysis, RNA* ; Signal Transduction ; Skin* ; Transcriptome ; Transient Receptor Potential Channels ; Up-Regulation ; Wound Healing