Fung-Wei Chang

Estrogen inhibits renal cell carcinoma cell progression through estrogen receptor-β activation.

Renal cell carcinoma (RCC) originates in the lining of the proximal convoluted tubule and accounts for approximately 3% of adult malignancies. The RCC incidence rate increases annually and is twofold higher in males than in females. Female hormones such as estrogen may play important roles during RCC carcinogenesis and result in significantly different incidence rates between males and females. In this study, we found that estrogen receptor β (ERβ) was more highly expressed in RCC cell lines (A498, RCC-1, 786-O, ACHN, and Caki-1) than in breast cancer cell lines (MCF-7 and HBL-100); however, no androgen receptor (AR) or estrogen receptor α (ERα) could be detected by western blot. In addition, proliferation of RCC cell lines was significantly decreased after estrogen (17-β-estradiol, E2) treatment. Since ERβ had been documented to be a potential tumor suppressor gene, we hypothesized that estrogen activates ERβ tumor suppressive function, which leads to different RCC incidence rates between males and females. We found that estrogen treatment inhibited cell proliferation, migration, invasion, and increased apoptosis of 786-O (high endogenous ERβ), and ERβ siRNA-induced silencing attenuated the estrogen-induced effects. Otherwise, ectopic ERβ expression in A498 (low endogenous ERβ) increased estrogen sensitivity and thus inhibited cell proliferation, migration, invasion, and increased apoptosis. Analysis of the molecular mechanisms revealed that estrogen-activated ERβ not only remarkably reduced growth hormone downstream signaling activation of the AKT, ERK, and JAK signaling pathways but also increased apoptotic cascade activation. In conclusion, this study found that estrogen-activated ERβ acts as a tumor suppressor. It may explain the different RCC incidence rates between males and females. Furthermore, it implies that ERβ may be a useful prognostic marker for RCC progression and a novel developmental direction for RCC treatment improvement.

Anti-inflammatory and anti-angiogenic effects of flavonoids isolated from Lycium barbarum Linnaeus on human umbilical vein endothelial cells

Anti-inflammatory and anti-angiogenic effects of flavonoids isolated from Lycium barbarum fruits, a traditional Chinese medicine, on human umbilical vein endothelial cells (HUVECs) were investigated. Initially, flavonoids were extracted with 80% ethanol and separated using a Cosmosil 140 C18-OPN column, with the acidic fraction eluted with deionized water being composed of chlorogenic acid, caffeoyl quinic acid, caffeic acid and p-coumaric acid and the neutral fraction eluted with methanol composed of quercetin-diglycoside, rutin and kaempferol-O-rutinoside. Flavonoid extract was effective in inhibiting expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1) induced by TNF-α in HUVECs. The RT-PCR analysis indicated that ICAM-1 mRNA induced by TNF-α was inhibited by flavonoid extract. The flavonoid extract attenuated TNF-α-induced IκB phosphorylation as well as NF-κB, p65 and p50 translocation from cytosol to nucleus, through inhibition on TNF-α- and H(2)O(2)-induced intracellular reactive oxygen species (ROS) production. For the anti-angiogenic study, the flavonoid extract inhibited vascular endothelial growth factor (VEGF)-induced cell proliferation and migration in HUVECs, as well as angiogenesis. However, the flavonoid extract did not inhibit VEGF signaling. Surprisingly, HUVECs adhesion to the extracellular matrix was compromised and adhesion-induced signaling was retarded by the flavonoid extract.

Early diagnosis of ovarian pregnancy by ultrasound

A 30-year-old woman had revealed a history of primary infertility, endometriosis and oligomenorrhea. Her hysterosalpingography demonstrated an otherwise normal image without uterovarian fistula. This patient presented with lower abdominal pain and vaginal spotting for consecutive 3 days and last menstrual period 5 weeks ago. There is no clear identification of gestational development at such an early period. One week later, she developed moderate tenderness over the right lower abdominal quadrant with apparent muscle guarding. A transvaginal ultrasonography revealed a gestational-free uterus and an echogenic mass within the right ovary (Fig. 1a). The serum betahCG level was 4879 mIUyml, which indicated an ectopic pregnancy. Two days later, the vaginal ultrasonography revealed the mass comprising normal ovarian tissue with a corpus luteum (Fig. 1b). The trend of serum beta-hCG level maintained a plateau change of 4530 mIUyml. A laparoscopy revealed an apparent blood clot in the pelvic region, and an ovarian mass. The uterus, fallopian tubes and left ovary all appeared to be normal in appearance apart from their being partially covered

The triterpenoids of Hibiscus syriacus induce apoptosis and inhibit cell migration in breast cancer cells

BackgroundBreast cancer-related mortality increases annually. The efficacy of current breast cancer treatments is limited, and they have numerous side effects and permit high recurrence. Patients with estrogen receptor (ER)-negative or triple-negative breast cancer are particularly difficult to treat. Treatment for this type of cancer is lacking, and its prognosis is poor, necessitating the search for alternative treatments.MethodsThis study screened Chinese herb Hibiscus syriacus extracts and identified a novel anti-cancer drug for patients with ER-negative breast cancer. The inhibitory effects on cell viability and migration were evaluated for each compound, and the molecular regulatory effects were evaluated on both mRNA and protein levels.ResultWe found several triterpenoids including betulin (K02) and its derivatives (K03, K04, and K06) from H. syriacus inhibited human triple-negative breast cancer cell viability and migration but revealed smaller cytotoxic effects on normal mammalian epithelial cells. Betulin and its derivatives induced apoptosis by activating apoptosis-related genes. In addition, they activated p21 expression, which induced cell cycle arrest in breast cancer cells. Betulin (K02) and betulinic acid (K06) had stronger inhibitory effects on cell viability and migration than K03 and K04.ConclusionsH. syriacus extracts might inhibit breast cancer cell viability and induce apoptosis by activating p53 family regulated pathways and inhibiting AKT activation. H. syriacus extracts may provide important insight into the development of novel alternative therapies for breast cancer.

Scabies increased the risk and severity of COPD: a nationwide population-based study.

Background Scabies is a common parasitic infectious disease, and COPD is a major pulmonary disease. However, there have been no previous studies that have investigated the relationship between scabies and COPD. Materials and methods This nationwide population-based study included a total of 3,568 patients with scabies as the study group and 14,255 patients as a control group. We followed up patients in both groups for a 5-year period to identify any new diagnoses of COPD. We then followed them up for an additional 2-year period to determine the severity of any newly diagnosed cases of COPD as indicated by acute respiratory events. Cox proportional hazard regression analyses were performed to calculate the hazard ratio (HR) of COPD during the 5-year follow-up period and COPD complication during the additional 2-year follow-up period. Results Of the 17,823 patients in the study, 2,765 (15.5%) were newly diagnosed with COPD during the 5-year follow-up period; 904 (32.7%) were from the scabies group; and 1,861 (67.3%) were from the control group. Compared to the patients without scabies, the adjusted HR (aHR) for COPD for the subjects with scabies was 1.72 (95% CI: 1.59–1.87) during the 5-year follow-up period. For those newly diagnosed with COPD, the aHR for COPD with acute exacerbation was 1.85 (95% CI: 1.67–2.06), the aHR for COPD with pneumonia was 3.29 (95% CI: 2.77–3.92), the aHR for COPD with acute respiratory failure was 4.00 (95% CI: 3.08–5.19), and the aHR for COPD with cardiopulmonary arrest was 3.95 (95% CI: 2.25–6.95) during the additional 2-year follow-up period. Conclusion The results of this study indicate a 72% increased risk for COPD among patients with scabies. The results also reveal an increased risk of severe COPD complications such as acute respiratory failure, cardiopulmonary arrest, pneumonia, and acute exacerbation among patients with scabies. This useful information may help physicians in treating scabies and remaining alert to the potential development of COPD and its severe complications.

The effects of climate factors on scabies. A 14-year population-based study in Taiwan

Scabies is a common infectious disease and can cause severe outbreaks if not controlled quickly. Besides personal contact history, environmental factors are also important. This study analyzed the effects of environmental climate factors on the incidence of scabies in Taiwan. We conducted a 14-year nationwide population-based study: a total of 14,883 patients with scabies infestation were enrolled. Monthly climate data were collected from Taiwan’s Central Weather Bureau, including data on temperature, relative humidity, total rainfall, total rain days, and total sunshine hours. The linear relationships between these climate factors and scabies infestations or other risk factors were examined by Pearson’s correlation analysis. Overall, the incidence of scabies was negatively correlated with temperature (γ = −0.152, p < 0.001), while being positively correlated with humidity (γ = 0.192, p < 0.001). This useful information may provide evidence for lowering humidity at nursing facilities, hospitals, and military camps with scabies infestations, which may help to reduce its spread and prevent outbreaks.

An angular pregnancy of a bicornuate uterus

A 30-year-old woman with a prior cesarean delivery, presented with abdominal spasmodic pain in the left lower quadrant and intermittent vaginal bleeding at 9 weeks’ pregnancy. Gynecologic sonographic examination at our emergency room revealed a cornual pregnancy in a bicornuate uterus (Fig. 1a). The symptoms intensified, and the patient was diagnosed with an angular pregnancy of a bicornuate uterus. She was treated successfully with dilation and curettage under laparoscopic guidance, and required no further invasive surgery. She was symptom free immediately after surgery and resumed a normal menstrual cycle approximately 2 months later. Gynecologic sonography revealed a mild asymmetric enlargement of the left side of the bicornuate uterus (Fig. 1b). Angular pregnancy, a type of cornual pregnancy, is a rare obstetrical complication and a life-threatening condition. The implantation of the embryo in the lateral angle of the uterine cavity, medial to the uterotubal junction and round ligament, should be distinguished from an interstitial pregnancy, which

EphA2 is a biomarker of hMSCs derived from human placenta and umbilical cord

OBJECTIVE The heterogeneous nature of mesenchymal stem cells (MSCs) and the absence of known MSC-specific biomarkers make it challenging to define MSC phenotypes and characteristics. In this study, we compared the phenotypic and functional features of human placenta-derived MSCs with those of human dermal fibroblasts in vitro in order to identify a biomarker that can be used to increase the purity of MSCs in a primary culture of placenta-derived cells. MATERIALS AND METHODS Liquid chromatography-tandem mass spectrometry analysis was used to analyze and compare the proteome of human placenta-derived MSCs with that of fibroblasts. Quantitative real-time polymerase chain reaction, immunofluorescence, and flow cytometry were used to determine expression levels of EphA2 in placenta-derived MSCs. EphA2-positive cells were enriched by magnetic-activated cell sorting or with a cell sorter. An shRNA-mediated EphA2 knockdown was used to assess the role of EphA2 in MSC response to Tumor necrosis factor (TNF)-α stimulation. RESULTS Analysis of proteomics data from MSCs and fibroblasts resulted in the identification of the EphA2 surface protein biomarker, which could reliably distinguish MSCs from fibroblasts. EphA2 was significantly upregulated in placenta-derived MSCs when compared to fibroblasts. EphA2 played an important role in MSC migration in response to inflammatory stimuli, such as TNF-α. EphA2-enriched MSCs were also more responsive to inflammatory stimuli in vitro when compared to unsorted MSCs, indicating a role for EphA2 in the immunomodulatory functionality of MSCs. CONCLUSION EphA2 can be used to distinguish and isolate MSCs from a primary culture of placenta-derived cells. EphA2-sorted MSCs exhibited superior responsiveness to TNF-α signaling in an inflammatory environment compared with unsorted MSCs or MSC-like cells.

Gene expression of human endometrial L-selectin ligand in relation to the phases of the natural menstrual cycle

This study investigates peptide components of L-selectin ligand (LSL) and their gene expressions in human endometrium during the natural menstrual cycle. We recruited 41 endometrial samples from reproductive-aged women with leiomyoma and undergoing hysterectomy and 11 endometrial samples from menopausal women as controls. Immunohistochemistry revealed strong MECA-79 expression from the early through the mid-secretory phase and low expression in menopausal endometrium. Five peptide components of LSL were detected in reproductive and menopausal endometrium by one-step quantitative RT-PCR: podocalyxin, endomucin, nepmucin, GlyCAM-1, and CD34. Endomucin differed significantly between the proliferative and early-secretory phases. CHST2 and CHST4 genes (which are involved in the generation of LSL epitopes) were expressed without significant differences among phases. The gene expression of progesterone receptor decreased from the proliferative to the late-secretory phase, and the difference was significant. However, estrogen receptor α expression showed stability among phases. The significant expression of endomucin between the proliferative and early-secretory phases might play a vital role in endometrial receptivity. Further studies are needed to investigate the factors that regulate the expression of endomucin and other LSL peptide components in different phases of the menstrual cycle.

Incidence of autoimmune diseases in patients with scabies: a nationwide population-based study in Taiwan

Scabies is a commonly occurring infectious immune-mediated inflammatory skin disease. Immune-mediated inflammatory processes are also observed in autoimmune diseases. There have been very few previous studies; however, that have investigated the possible association between scabies and autoimmune diseases. To address this research gap, we conducted a nationwide population-based cohort study that included a total of 4481 scabies patients and 16,559 control subjects matched by gender, age, insured region, urbanization and income. We tracked both cohorts for a 7-year period to identify the incidence of autoimmune diseases in both groups during that follow-up period. Relatedly, a Cox regression analysis was performed to calculate and compare the hazard ratio (HR) for autoimmune diseases of both groups. An overall increased risk for 19 autoimmune diseases was observed in the scabies patients, with an adjusted HR (aHR) of 1.14 (95% CI 1.04–1.25). Compared with the control group, the scabies patients exhibited increased risks of hypersensitivity vasculitis (aHR 5.44, 95% CI 1.64–18.07), dermatomyositis (aHR 4.91, 95% CI 1.80–13.38), polyarteritis nodosa (aHR 2.89, 95% CI 1.46–5.73), systemic lupus erythematosus (aHR 2.73, 95% CI 1.33–5.64), psoriasis (aHR 2.31, 95% CI 1.85–2.88), myasthenia gravis (aHR 2.01, 95% CI 1.31–3.12), type 1 diabetes mellitus (aHR 1.93, 95% CI 1.53–2.44), pernicious anemia (aHR 1.92, 95% CI 1.42–2.61), and rheumatoid arthritis (aHR 1.43, 95% CI 1.12–1.83). In conclusion, the associations between scabies and a variety of autoimmune diseases may exist. Further studies are needed to clarify the shared etiologies and relationships between scabies and autoimmune diseases.