51 research outputs found
Role of exosomal miR-141 in pro-metastatic tumor-stroma interactions in ovarian cancer
No full textMetastatic colonization is one of the critical steps in tumor metastasis. A pre-metastatic niche is required for metastatic colonization and is determined by tumor-stroma interactions, yet the mechanistic underpinnings remain incompletely understood. Previously, we showed that hsa-miR-141-3p (miR-141) is generally elevated and enhances anoikis resistance via targeting the KLF12/Sp1/survivin signaling cascade, facilitating metastatic cancer progression in ovarian cancer. Here, we report that Hsa-miR-141-3p (miR-141), an exosomal miRNA, is highly secreted by ovarian cancer cells and reprograms stromal fibroblasts into proinflammatory cancer-associated fibroblasts (CAFs), thereby facilitating metastatic colonization. A mechanistic study showed that miR-141 targeted Yes-associated protein (YAP1), a key effector of the Hippo pathway, promoting Tafazzin (TAZ), reducing nuclear YAP1/TAZ ratio and enhancing Tafazzin (TAZ)- and TEAD1-mediated transcriptional activation of the oncogenic factors GROα and EMMPRIN in stromal fibroblasts. Genetic inhibition of YAP1 induced a direct increase in transcription of GROα and EMMPRIN, in turn, forming an ideal pre-metastatic niche in tumor microenvironment (TME) under conditions of chronic inflammation favoring metastatic colonization and progression. Conversely, enforced expression of YAP1 markedly reduced the levels of GROα and EMMPRIN. Stromal-specific knockout (cKO) of Yap1 in a murine model shaped a GROα-enriched microenvironment and promoted tumor colonization in vivo, but this effect was reversed after Cxcr1/2 depletion in ovarian cancer cells. The YAP1/GROα correlation was demonstrated in clinical samples, highlighting the clinical relevance of this research and providing a potential therapeutic intervention for impeding premetastatic niche formation and metastatic progression of ovarian cancers.published_or_final_versionObstetrics and GynaecologyDoctoralDoctor of Philosoph
Study of nano-mechanical performance of pretreated natural fiber in ldpe composite for packaging applications
No full textIn this work, the effects of chemical pretreatment and different fiber loadings on mechanical properties of the composites at the sub-micron scale were studied through nanoindentation. The composites were prepared by incorporating choline chloride (ChCl) pretreated rice husk waste (RHW) in low-density polyethylene (LDPE) using melt processing, followed by a thermal press technique. Nanoindentation experiments with quasi continuous stiffness mode (QCSM) were performed on the surface of produced composites with varying content of pretreated RHW (i.e., 10, 15, and 20 wt.%). Elastic modulus, hardness, and creep properties of fabricated composites were measured as a function of contact depth. The results confirmed the appreciable changes in hardness, elastic modulus, and creep rate of the composites. Compliance curves indicated that the composite having 20 wt.% of pretreated RHW loading was harder compared to that of the pure LDPE and other composite samples. The values of elastic modulus and hardness of the composite containing 20 wt.% pretreated RHW were increased by 4.1% and 24% as compared to that of the pure LDPE, respectively. The creep rate of 42.65 nm/s and change in depth of 650.42 nm were also noted for the composite with RHW loading of 20 wt.%, which showed the substantial effect of holding time at an applied peak load of 100 mN. We believe that the developed composite could be a promising biodegradable packaging material due to its good tribo-mechanical performance.Rivers, Ports, Waterways and Dredging Engineerin
Longitudinal study on sexual function and quality of life in infertile couples undergoing intrauterine insemination
No full textBACKGROUND: Cross-sectional studies have shown that sexual dysfunction and poor quality of life were prevalent among couples undergoing assisted reproduction at specific time points, but nothing is known about how these outcomes change over the course of their intrauterine insemination (IUI) journey. AIM: We investigated the longitudinal changes in sexual function and quality of life of infertile couples undergoing IUI. METHODS: Sixty-six infertile couples completed an anonymous questionnaire at 3 time points: after IUI counseling (T1), 1 day before IUI (T2), and 2 weeks after IUI (T3). The questionnaire consisted of demographic data, Female Sexual Function Index (FSFI) or International Index of Erectile Function-5, and Fertility Quality of Life (FertiQoL). OUTCOMES: Descriptive statistics, significance testing with the Friedman test, and post hoc analysis with the Wilcoxon signed rank test were used to compare changes in sexual function and quality of life at different time points. RESULTS: Overall, 18 (26.1%), 16 (23.2%), and 12 (17.4%) women and 29 (42.0%), 37 (53.6%), and 31 (44.9%) men were at risk for sexual dysfunction at T1, T2, and T3, respectively. There were significant differences in mean FSFI scores in arousal (3.87, 4.06, 4.10) and orgasm (4.15, 4.24, 4.39) domains at T1, T2, and T3. After post hoc analysis, only the increase in mean orgasm FSFI scores between T1 and T3 was statistically significant. Men's FertiQoL scores remained high during IUI (74.33-75.63 out of 100). Men also scored significantly higher than women on all FertiQoL domains except environment at the 3 time points. Post hoc analysis showed significant improvement in women's FertiQoL domain scores between T1 and T2: mind-body, environment, treatment, and total. Women's FertiQoL score at T2 for the treatment domain was also significantly higher than that at T3. CLINICAL IMPLICATIONS: Men should not be neglected during IUI as their erectile function got worse in the process, with half of the men being affected. Although women's quality of life showed some improvement during IUI, most of their scores were lower than men's. STRENGTHS AND LIMITATIONS: The use of psychometrically validated questionnaires and a longitudinal approach are the major strengths; a small sample size and the lack of a dyadic approach are the major limitations. CONCLUSION: During IUI, women's sexual performance and quality of life improved. The proportion of men having erectile problems was high for this age group, but men's FertiQoL scores remained good and were better than their partners' throughout IUI
The Therapeutic Potential of Human Endometrial Mesenchymal Stem-like Cells (eMSC) using an Injured Endometrial Mouse Model
No full textMicroenvironmental regulation of human endometrial mesenchymal stem-like cells.
No full textTitle: Microenvironmental regulation of human endometrial mesenchymal stem-like cells. Authors: RWS Chan, MZ Cao, EHY Ng, WSB Yeung. Institution: The University of Hong Kong, Obstetrics & Gynecology, Hong Kong, Hong Kong; Shenzhen Key Laboratory of Fertility Regulation, The University of Hong Kong-Shenzhen Hospital. Study question: (25 words) Do myometrial cells function as niche cells regulating the biological activities of endometrial stem cells? Study answer: (25 words) Soluble factors derived from myometrial cells increased self-renewal and proliferation activities of endometrial mesenchymal stem-like cells (eMSCs) by activating WNT/β-catenin signaling. What is known already: (100 words) Adult stem cells contribute to regeneration of endometrium. Data from human and mouse endometrium localized eMSCs preferentially to regions adjacent to the myometrium. In mice, active β-catenin was highly expressed in proliferating endometrial label-retaining cells after parturition. We hypothesized that the myometrial cells provided niche signals regulating the biological activities of eMSCs. Study design, size, duration: (75 words) Sequential beading with magnetic beads coated with anti-CD140b and anti-CD146 antibodies was used to isolate eMSCs from endometrial tissues from proliferative (n = 24) and secretory (n = 16) phase. The eMSCs were seeded at low density, and indirectly co-cultured with myometrial cells at ratio of 1:90 for 15 days. Functional stem cell assays were performed and the proportion of cell expressing the eMSCs markers was evaluated. Participants/materials, setting, methods: (75 words) Proliferative and secretory phase samples obtained from women aged 35- to 50-years undergoing total abdominal hysterectomy. Endometrial cells were isolated enzymatically and the percentage of eMSCs after co-culture with myometrial cells was analyzed by flow cytometry. Western blot analysis for active β-catenin validated the activation of Wnt/β-catenin signaling. The role of WNT/β-catenin signaling in eMSCs self-renewal was confirmed by gain-of (activator: Wnt3a conditioned medium and recombinant WNT3A) and loss-of (inhibitors: XAV939 and IWP-2) function approaches. Main results and role of chance: (200 words) In vitro co-culture of myometrial cells enhanced the colony forming and self-renewal ability of eMSCs. The expanded eMSCs after coculture retained multipotent characteristic and exhibited a greater total cell output when compared to medium alone culture. The level of active β-catenin in eMSCs increased significantly after co-culture with myometrial cells suggesting activation of the WNT/β-catenin signaling. Secretory factors from myometrial cells produced the same stimulatory effect on eMSCs. The functional WNT/β-catenin signaling in eMSCs self-renewal was determined with WNT activator (Wnt3a conditioned medium) and WNT inhibitors (XAV939 and IWP-2). Addition of Wnt3a CM or recombinant WNT3A increased the clonogenic activity and number of eMSCs. While, the stimulatory effect of myometrial cells on eMSCs was suppressed by the Wnt inhibitors. Limitations, reasons for caution: (50 words) The behavior of the cells may be altered during culture. The functionality of myometrial derived factors on eMSCs needs to be determined with in vivo studies. Wider implication of the findings: (50 words) Myometrial cells provide paracrine factors to eMSCs via the Wnt/β-catenin signaling. Secretory factors derived from the myometrial cells offer a specialized microenvironment modulating eMSC activities. By gaining a better understanding of the niche composition, it will be possible to recreate a milieu for stem cell expansion and control their biological activities. Study funding: This project was supported by Research Grant Council in Hong Kong.abstrac
Knowledge, Attitude And Ethical Consideration Of Chinese Couples Requesting Preimplantation Genetic Testing In Hong Kong
No full textAim: Increasing preimplantation genetic testing (PGT) cycles are being performed in Hong Kong. This study aims to evaluate the knowledge, attitude and ethical consideration of Chinese couples toward PGT.
Methods: Couples requesting PGT between June 2013 and March 2014 were invited to complete a questionnaire.
Results: Total 49 couples (49 women, 47 men) completed the questionnaires. Eighteen couples (37%) were waiting for PGT (pre‐PGT group), 15 couples (31%) were undergoing PGT (PGT group) and 16 couples (32%) had completed at least one PGT cycle (post‐PGT group). Only 53% of the couples could tell the recurrent risk, and 31% (with monogenic disorders) could tell the mode of inheritance of their condition. The acceptability of PGT (>80%) and attitude toward the embryo fate (58–78%) were good. The post‐PGT group had more concern than the PGT and pre‐PGT groups on the prenatal diagnostic testing (**P = 0.007). 12.5% of the couples worried about the transfer of healthy embryos with carrier state and they all had monogenic disorders. If the prenatal testing confirmed an affected fetus, a higher percentage (32%) in the Post‐PGT group disagreed to terminate the pregnancy in contrast to a much lower 6% in the pre‐PGT group (**P = 0.02). Three‐quarter of the couples opted to tell their child about their conception through PGT.
Conclusion: Chinese couples in Hong Kong had an overall good acceptability and positive attitude toward PGT. We appreciate the difficulties the couples have gone through PGT. A checklist on what to cover pre‐during‐post‐PGT in the counseling process is needed.postprin
Transient Giant R-Wave, Right Axis Deviation, and Intraventricular Conduction Delay during Exercise Treadmill Testing: A Case Report
No full textA 53-year-old man complained of chest pain during an exercise treadmill test. Electrocardiogram revealed transient giant R-wave, right-axis deviation, intraventricular conduction delay, and ST-segment elevation in the inferolateral leads. Subsequent coronary angiography showed an 80% lesion in mid part of a nondominant left circumflex artery, whereas the other coronary arteries had mild atherosclerosis only. Percutaneous coronary intervention and stenting was performed on the left circumflex artery lesion. A follow-up exercise thallium scan 3 months later still showed an intermediate-sized, mild reversible perfusion defect in the inferior and lateral wall but the giant R-wave ECG pattern was not inducible anymore. Restudy coronary angiography showed no in-stent restenosis, but there was disease progression in the midpart of the right coronary artery. The initial electrocardiographic pattern is typical of the "giant R-wave syndrome." Severe coronary spasm superimposed on the underlying mild atherosclerotic lesion of the right coronary artery is hypothesized to be the cause of the initial event. Ad hoc direct stenting was performed on the right coronary artery lesion. The patient remained symptom-free with a normal thallium scan 9 months later.link_to_subscribed_fulltex
Is it safe to reuse single-use catheter for diagnostic and therapeutic electrophysiological procedures?
No full textDefibrillation - Guided Radiofrequency Ablation of Atrial Fibrillation Secondary To An Atrial Focus
No full text- …
