Up-regulation of Bax and endonuclease G, and down-modulation of Bcl-XL involved in cardiotoxin III-induced apoptosis in K562 cells

Sheng-Huei Yang,Ching-Ming Chien,Mei-Chin Lu,Yi-Hsiung Lin,Xiu-Wei Hu,Shinne-Ren Lin 생화학분자생물학회 2006 Experimental and molecular medicine Vol.38 No.4

Cardiotoxin III (CTX III), a basic polypeptide with 60 amino acid residues isolated from Naja naja atra venom, has been reported to have anticancer activity. CTX III-induced K562 cell apoptosis was confirmed by DNA fragmentation (DNA ladder, sub-G1 for-mation) and phosphatidylserine (PS) externalization with an IC50 value of 1.7 g/ml at 48 h. A mechanistic analysis demonstrated that CTX III-induced apop-totic cell death was accompanied by up-regulation of both Bax and endonuclease G (Endo G), and downregulation of Bcl-XL. CTX III had no effect on the levels of Bcl-2, Bid, XIAP survivin, and AIF proteins. CTX III treatment caused loss of the mitochondrial membrane potential (Ψm), release of mitochon-drial cytochrome c to the cytosol, and activation of both caspase-9 and -3. CTX III-induced apoptosis was significantly blocked by the broad-spectrum cas-pase inhibitor Z-VAD-FMK. However, CTX III did not generate reactive oxygen species (ROS) and talase, did not block CTX III-induced apoptosis in K562 cells. Modulation of Bax, Bcl-XL, and the Endo G proteins, release of mitochondrial cytochome c, and activation of caspase-3 and -9 all are involved in the CTX III-triggered apoptotic process in human leukemia K562 cells.

Fixed-point theory for k-set contraction

Chi-Ming Chen,Tong-Huei Chang,Chi-Lin Yen 대한수학회 2004 대한수학회지 Vol.41 No.2

In this note, we get some generalized KKM theorems for the k-set contraction mapping on the nearly-convex sets.

Infusion of Human Mesenchymal Stem Cells Improves Regenerative Niche in Thioacetamide-Injured Mouse Liver

Kao Ying-Hsien,Lin Yu-Chun,Lee Po-Huang,Lin Chia-Wei,Chen Po-Han,Tai Tzong-Shyuan,Chang Yo-Chen,Chou Ming-Huei,Chang Chih-Yang,Sun Cheuk-Kwan 한국조직공학과 재생의학회 2020 조직공학과 재생의학 Vol.17 No.5

Background: This study investigated whether xenotransplantation of human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) reduces thioacetamide (TAA)-induced mouse liver fibrosis and the underlying molecular mechanism. Methods: Recipient NOD/SCID mice were injected intraperitoneally with TAA twice weekly for 6 weeks before initial administration of WJ-MSCs. Expression of regenerative and pro-fibrogenic markers in mouse fibrotic livers were monitored post cytotherapy. A hepatic stallate cell line HSC-T6 and isolated WJ-MSCs were used for in vitro adhesion, migration and mechanistic studies. Results: WJ-MSCs were isolated from human umbilical cords by an explant method and characterized by flow cytometry. A single infusion of WJ-MSCs to TAA-treated mice significantly reduced collagen deposition and ameliorated liver fibrosis after 2-week therapy. In addition to enhanced expression of hepatic regenerative factor, hepatocyte growth factor, and PCNA proliferative marker, WJ-MSC therapy significantly blunted pro-fibrogenic signals, including Smad2, RhoA, ERK. Intriguingly, reduction of plasma fibronectin (pFN) in fibrotic livers was noted in MSC-treated mice. In vitro studies further demonstrated that suspending MSCs triggered pFN degradation, soluble pFN conversely retarded adhesion of suspending MSCs onto type I collagen-coated surface, whereas pFN coating enhanced WJ-MSC migration across mimicked wound bed. Moreover, pretreatment with soluble pFN and conditioned medium from MSCs with pFN strikingly attenuated the response of HSC-T6 cells to TGF-β1-stimulation in Smad2 phosphorylation and RhoA upregulation. Conclusion: These findings suggest that cytotherapy using WJ-MSCs may modulate hepatic pFN deposition for a better regenerative niche in the fibrotic livers and may constitute a useful anti-fibrogenic intervention in chronic liver diseases.

VEGF and FGF2 improve revascularization, survival, and oocyte quality of cryopreserved, subcutaneously transplanted mouse ovarian tissues

( Cheng-en Hsieh ),( Yuh-ming Hwu ),( Sheng-hsiang Li ),( Chung-hao Lu ),( Ming-huei Lin ),( Robert Kuo-kuang Lee ) 대한산부인과학회 2016 대한산부인과학회 학술대회 Vol.102 No.-

Objective: To investigate the effect of vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2) on revascularization, survival, and oocyte quality of cryopreserved, subcutaneously transplanted mouse ovarian tissue. Methods: Outbred ICR mice (n = 112) were used as the animal model. Vitrified mouse ovarian tissues were treated without (control group) or with VEGF and FGF2 before autologous subcutaneous transplantation. After transplantation for 2 or 3 weeks, grafts’ survival, angiogenesis, and oocyte quality were examined. Results: VEGF and FGF2 promoted revascularization and significantly increased the survival rate of subcutaneously transplanted cryopreserved ovarian tissues compared with the untreated grafted control. The two growth factors did not show long-term effects on the ovarian grafts. In contrast to the untreated ovarian grafts, active folliculogenesis was revealed as the number of various follicles was significantly higher or had an increased trend in the VEGF and FGF2-treated ones. Though the fertilization rate had no differences between VEGF/FGF2 and control group; however, the oocyte quality was much better in the VEGF/FGF2-treated grafts as demonstrated by the higher ratio of blastocyst development. Conclusions: Introducing of angiogenic factors such as VEGF and FGF2 may be a promising strategy to improve revascularization, survival, and oocyte quality of cryopreserved, subcutaneously transplanted mouse ovarian tissue.

Maintenance of pegylated liposomal doxorubicin/carboplatin in patients with advanced ovarian cancer: randomized study of an Asian Gynecologic Oncology Group

Chyong-Huey Lai,Elizabeth Vallikad,Hao Lin,Lan-Yan Yang,Shih-Ming Jung,Hsueh-Erh Liu,Yu-Che Ou,Hung-Hsueh Chou,Cheng-Tao Lin,Huei-Jean Huang,Kuan-Gen Huang,Jiantai Qiu,Yao-Ching Hung,Tzu-I Wu,Wei-Yang 대한부인종양학회 2020 Journal of Gynecologic Oncology Vol.31 No.1

Objectives: An Asian Gynecologic Oncology Group phase III randomized trial was conducted to determine whether maintenance chemotherapy could improve progression-free survival (PFS) in stages III/IV ovarian cancer. Methods: Between 2007 and 2014, 45 newly-diagnosed ovarian cancer patients were enrolled after complete remission and randomized (1:1) to arm A (4-weekly carboplatin area under the curve 4 and pegylated liposomal doxorubicin [PLD] 30 mg/m2, n=24) for 6 cycles or arm B (observation, n=21). The primary end-point was PFS. A post hoc translational study was conducted to deep sequence BRCA/homologous recombination deficiency (HRD) genes, because BRCA/HRD mutations (BRCA/HRDm) are known to be associated with better prognosis. Results: Enrollment was slow, accrual was closed when 7+ years had passed. With a median follow-up of 88.9 months, the median PFS was significantly better in arm A (55.5 months) than arm B (9.2 months) (hazard ratio [HR]=0.40; 95% confidence interval [CI]=0.19–0.87; p=0.020), yet the median overall survival was not significantly different in arm A (not reached) than arm B (95.1 months) (p=0.148). Overall grade 3/4 adverse events were more frequent in arm A than arm B (60.9% vs 0.0%) (p<0.001). Quality of life was generally not significantly different. Distribution of BRCA1/2m or BRCA/HRDm was not significantly biased between the two arms. Wild-type BRCA/non-HRD subgroup seemed to fare better with maintenance therapy (HR=0.35; 95% CI=0.11–1.18; p=0.091). Conclusions: Despite limitations in small sample size, it suggests that maintenance carboplatin-PLD chemotherapy could improve PFS in advanced ovarian cancer.

Proton Pump Inhibitor-unresponsive Laryngeal Symptoms Are Associated With Psychological Comorbidities and Sleep Disturbance: A Manometry and Impedance-pH Monitoring Study

Wen-Hsuan Tseng,Wei-Chung Hsu,Tsung-Lin Yang,Tzu-Yu Hsiao,Jia-Feng Wu,Hui-Chuan Lee,Hsiu-Po Wang,Ming-Shiang Wu,Ming-Shiang Wu,Ping-Huei Tseng 대한소화기 기능성질환∙운동학회 2023 Journal of Neurogastroenterology and Motility (JNM Vol.29 No.3

Background/AimsLaryngeal symptoms are largely treated with empiric proton pump inhibitor (PPI) therapy if no apparent pathology shown on ear, nose, and throat evaluation and reflux-related etiologies are suspected. However, treatment response remains unsatisfactory. This study aimed to investigate the clinical and physiological characteristics of patients with PPI-refractory laryngeal symptoms. MethodsPatients with persistent laryngeal symptoms despite PPI treatment for ≥ 8 weeks were recruited. A multidisciplinary evaluation comprising validated questionnaires for laryngeal symptoms (reflux symptom index [RSI]), gastroesophageal reflux disease symptoms, psychological comorbidity (5-item brief symptom rating scale [BSRS-5]) and sleep disturbance (Pittsburgh sleep quality index [PSQI]), esophagogastroduodenoscopy, ambulatory impedance-pH monitoring, and high-resolution impedance manometry were performed. Healthy asymptomatic individuals were also recruited for comparison of psychological morbidity and sleep disturbances. ResultsNinety-seven adult patients and 48 healthy volunteers were analyzed. The patients had markedly higher prevalence of psychological distress (52.6% vs 2.1%, P < 0.001) and sleep disturbance (82.5% vs 37.5%, P < 0.001) than the healthy volunteers. There were significant correlations between RSI and BSRS-5 scores, and between RSI and PSQI scores (r = 0.26, P = 0.010, and r = 0.29, P = 0.004, respectively). Fifty-eight patients had concurrent gastroesophageal reflux disease symptoms. They had more prominent sleep disturbances (89.7% vs 71.8%, P < 0.001) than those with laryngeal symptoms alone but similar reflux profiles and esophageal motility. ConclusionsPPI-refractory laryngeal symptoms are mostly associated with psychological comorbidities and sleep disturbances. Recognition of these psychosocial comorbidities may help optimize management in these patients.

Activation of Small GTPases RhoA and Rac1 Is Required for Avian Reovirus p10-induced Syncytium Formation

Hung-Jen Liu,Ping-Yuan Lin,Ling-Rung Wang,Hsue-Yin Hsu,Ming-Huei Liao,Wen-Ling Shih 한국분자세포생물학회 2008 Molecules and cells Vol.26 No.4

The first ORF of the ARV S1133 S1 segment encodes the nonstructural protein p10, which is responsible for the induction of cell syncytium formation. However, p10-dependent signaling during syncytium formation is fully unknown. Here, we show that dominant negative RhoA, Rho inhibitor C3 exoenzyme, ROCK/Rho-kinase inhibitor Y-27632 and Rac1 inhibitor NSC23766 inhibit p10-mediated cell fusion. p10 over-expression is concomitant with activation and membrane translocation of RhoA and Rac1, but not cdc42. RhoA and Rac1 downstream events, including JNK phosphorylation and transcription factor AP-1 and NF-B activation, as well as MLC expression and phosphorylation are simultaneously activated by p10. p10 point mutant T13M possessed 20% fusion-inducing ability and four p10 fusion-deficient mutants V15M, V19M, C21S and L32A reduced or lost their ability to activate RhoA and Rac1 signaling. We conclude that p10-mediated syncytium formation proceeds by utilizing RhoA and Rac1-dependent signaling.