Popular Science Format in Academic and Research Column

[Introduction]

Endometriosis is a chronic inflammation-associated and common benign gynecological disorder. It affects 6–10% of women of reproductive age with syndromes, including dysmenorrhea, dyspareunia, and infertility. Because endometriosis recurrence following conservative surgery is relatively high, it substantially affects patients’ daily activities.   

[Lost way of endometrial tissue]

What is the pathogenesis of endometriosis? The wildly accepted hypothesis nowadays is the “retrograde menstruation/transplantation theory. The endometrial tissue shed during the menstrual cycle flow from the uterus into the peritoneal cavity. The retrograded cells or tissue are cleared by white blood cells. During this process, it would locally happen mild and transient inflammation in peritoneal cavity. If the process between clearance and inflammation keeps balance, the ectopic endometrial tissue can be effectively cleared and the inflammation would not damage the tissue in peritoneal cavity. Therefore, the lost-way endometrial tissue would not become endometriotic tumor and disturb daily activity in women of reproductive age.     

[Dysregulated inflammation]

What might disturb the balance between clearance and inflammation when retrograde tissue loses its way into peritoneal cavity? The research team led by Dr. Jau-Ling Suen at Kaohsiung Medical University discovered that the high local activity of anti-inflammatory cytokine IL-10 may promote the growth of the endometriotic tissue. It has been demonstrated that IL-10 can control unwanted inflammation to avoid tissue damage; however, high activity or level of IL-10 may inhibit the functions of white blood cells and diminish the clearance of ectopic tissue. In addition, Dr. Suen and her colleges discovered that IL-10 can promote angiogenesis through IL-10R signaling in vitro and in vivo, including a murine model as well as a zebra fish model. Thus, the IL-10-mediated angiogenesis may promote the growth of endometriotic lesions through enhancing angiogenesis during the early stage of endometriosis. 

[The dual activity of IL-10]

These findings discovered by Dr. Suen’s team suggest that the dual functions of IL-10 with respect to suppressing immunity against unwanted cells and promoting angiogenesis in the microenvironment may substantially contribute to the development of endometriosis. The next question is which immune cell type can secrete IL-10 in the microenvironment, particularly during the early stage of disease? Using a surgery-induced endometriosis murine model, Dr. Suen’s team demonstrated that local plasmacytoid dendritic cell (pDC), a key innate cell type in viral immunity, can secrete IL-10 to enhance angiogenesis in and promote growth of endometriotic lesions. In addition, IL-10–secreting pDCs have been found in the human endometrioma tissues, in which higher percentages of cells express IL-10 receptor and angiogenic marker CD31 compared with the corresponding normal counterparts.

[Conclusion]

We continue to put effort in elucidating the pathogenic role of IL-10–secreting pDCs and developing strategy targeting the IL-10–IL-10 receptor pathway in the endometriotic milieu.

Graphical Abstract

Figure. The cartoon shows the effect and immune cell sources of IL-10 during the early and late stages of endometriosis. During the menstrual cycle and the early stage of endometriosis, retrograded endometrial cells or tissue enter peritoneal cavity. Lesion plasmacytoid dendritic cells (pDCs) may produce IL-10 in response to unwanted cells. Local IL-10 further promotes lesion growth by either suppressing anti-ectopic fragment immunity or stimulating angiogenesis. During the late stage of disease, the complex interaction among genetic factors, endogenous hormones, environmental endocrine disruptors (EEDs), and impaired immune surveillance leads to chronic inflammation. In the context of chronic inflammation in the peritoneal cavity, other immune cells can secrete IL-10 and other mediators to further promote the growth and maintenance of ectopic implants. [The figure is cited from Suen et al. 2019. (J Pathol. 2019 Dec;249(4):485-497)]

Main researcher Intro.

1.        Dr. Jau-Ling Suen, the first author, at Kaohsiung Medical University study the role of innate immune cells in the pathogenesis of allergic asthma and endometriosis.

2.        Dr. Eing-Mei Tsai, the corresponding author, a gynecologist and reproductive endocrinologist, at Kaohsiung Medical University Hospital. She has devoted in the mechanistic study in endometriosis.

3.        Dr. Tzyh-Chyuan Hour, the equally contributed corresponding author, at Kaohsiung Medical University focus on the mechanistic study in prostate cancer and angiogenesis.

Author Email

jlsuen@kmu.edu.tw

Paper cited from: J Pathol. 2019 Dec;249(4):485-497. doi: 10.1002/path.5339.

Paper online website: https://pubmed.ncbi.nlm.nih.gov/31418859/

Finding an oral potentially malignant disorder in screening program is related to early diagnosis of oral cavity cancer-Experience from real world evidence.

This paper is practiced by Dr. Pei-Shan Ho, Dr. Wen-Chen Wang, and Dr. Yi-Hsin Yang, and published in “Oral Oncology”, which is top 10% in (the ranking is 3/91=3.3% o f the Dentistry, Oral surgery and Medicine in 2017 JCR).

The Objectives of this study are to evaluate the effectiveness of the Taiwan Oral Mucosal Screening (TOMS) program in stage-shift among oral cavity cancer patients, and identifies the related factors with early cancer diagnosis. This retrospective cohort study used the Taiwan Cancer Registry (TCR), TOMS and

Taiwan Death Registry (TDR) databases. We identified oral cavity cancer patients (ICD-C-O: C00-C06) from the TCR during 2012–2015. Patients’ screening history, first screening status and subsequent screenings were

analyzed with cancer stages and survival outcomes.

The major results of this study is that the 5-year survival rates for stages 0–4 were 83.9%, 82.1%, 72.7%, 60.1% and 38.0%. Among 18,625 patients identified from the TCR, 37% did not have any prior screenings. Patients with prior positive or negativescreenings all had better survival rates (3-year: 71.4% and 68.7% vs. 63.5%, Log-rank p-value < 0.0001). Thebest chance for early-stage diagnosis occurs in oral potentially malignant disorder (OPMD, OR=1.99, 95% CI=1.78–2.22, p < 0.0001) patients at their first screenings. The hazard ratios (HR) for patients with prior screenings indicated a significant survival benefit. The group of incomplete diagnosis confirmation also has better survival (HR=0.78, 95% CI=0.81–0.93, p < 0.0001), and a greater chance of early diagnosis at

subsequent screenings. Some important conclusions was found in this study.  While TOMS improved stage-shift for early cancer diagnosis, we found no obvious differences in participants with cancers at screening (stages 0–1: 26.3% vs. 27.8% in non-screening group). Survival benefit and early diagnosis are found in most of screening groups, and identifying an OPMD is particularly essential to early diagnosis of oral cavity cancer patients.

Research available at :https://pubmed.ncbi.nlm.nih.gov/30732947/

Endotoxin is the constituent of the cell wall of gram-negative bacteria that initiates the inflammatory response. Previous studies showed consistent results that airborne endotoxin exposure may increase the risk of respiratory symptoms in asthmatic children. Moreover, previous studies displayed that the air pollutants- nitrogen dioxide (NO₂) and nicotine may modify the association between airborne endotoxin and asthma outcome (acute visit, symptoms, etc.) and airway inflammation (the fractional concentration of exhaled nitric oxide) in asthmatic children.  

So far, limited studies have explored the effects of interactions between airborne endotoxin and air pollutants. The team led by Pei-Shih Chen, the Chair of Public Health of Kaohsiung Medical University, evaluated whether indoor air pollutants in a heavy industrial city, including NO2, PM, the carbon monoxide (CO), carbon dioxide (CO2), sulfur dioxide (SO2), and ozone (O3), can modify the association between indoor airborne endotoxin and lung function. 120 elementary school-age children in Kaohsiung City, Taiwan was recruited. Airborne endotoxin and air pollutants were collected for 24 hours in living rooms while schoolchildren’s lung function was measured. The modification of air pollutants on the relationship between airborne endotoxin and children’s lung function was estimated after adjusting the gender, age, height, weight, and case-control status. The team in collaborating with Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston, TX, United States, found that household O3 and PM can modify the association between household airborne endotoxin and lung functions. Our findings suggest that the combination of higher concentrations of O3 or PM10 exposure and concomitant indoor airborne endotoxin exposure may affect schoolchildren’s lung function in a heavy industrial city. These findings also highlight the importance of understanding the complexity of indoor exposures and their effects on lung functions to develop effective approaches to environmental control. The results have been published in the journal Science of the Total Environment .

Graphical Abstract

Our findings suggest that the combination of higher concentrations of O3 or PM10 exposure and concomitant indoor airborne endotoxin exposure may affect schoolchildren’s lung function in a heavy industrial city.

Main researcher Intro.

Researcher Pei-Shih Chen

Author Email

pschen@kmu.edu.tw

Paper cited from:

Science of the Total Environment 705 (2020) 135810

Research Paper available online on website

https://www.sciencedirect.com/science/article/pii/S004896971935805X