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Objective: Endometriosis is a bothersome disease affected women worldwide, the mechanism of disease development is still under investigation. Several inflammatory responses after clinical hyaluronic acid (HA) use were reported. Cyclooxygenase (COX)-2 mediated inflammation pathway is involved in the pathogenesis of endometriosis. Thus, we tried to investigate the inflammatory role of hyaluronic acid in endometriosis. Materials and methods: Peritoneal fluid was collected in endometriosis and disease-free patients for the measurement of HA. Endometriotic stromal cells were treated with IL-1β and HA and expression of COX-2 was evaluated. Mice model of endometriosis was established and treated with fluid or gel form of HA. Endometriotic lesion size and weight were recorded and level of COX-2 was evaluated by immunohistochemistry staining. Results: The level of HA in the peritoneal fluid had no statistically significant difference between normal, early and advanced stage endometriosis patients. The overexpression of COX-2 protein was detected when treating endometriotic stromal cell with HA in the presence of IL-1β (P

Metastatic cancer cells are frequently deficient in WWOX protein or express dysfunctional WWOX (designated WWOXd). Here, we determined that functional WWOX-expressing (WWOXf) cells migrate collectively and expel the individually migrating WWOXd cells. For return, WWOXd cells induces apoptosis of WWOXf cells from a remote distance. Survival of WWOXd from the cell-to-cell encounter is due to activation of the survival IκBα/ERK/WWOX signaling. Mechanistically, cell surface epitope WWOX286-299 (repl) in WWOXf repels the invading WWOXd to undergo retrograde migration. However, when epitope WWOX7-21 (gre) is exposed, WWOXf greets WWOXd to migrate forward for merge. WWOX binds membrane type II TGFβ receptor (TβRII), and TβRII IgG-pretreated WWOXf greet WWOXd to migrate forward and merge with each other. In contrast, TβRII IgG-pretreated WWOXd loses recognition by WWOXf, and WWOXf mediates apoptosis of WWOXd. The observatons suggest that normal cells can be activated to attack metastatic cancer cells. WWOXd cells are less efficient in generating Ca2+ influx and undergo non-apoptotic explosion in response to UV irradiation in room temperature. WWOXf cells exhibit bubbling cell death and Ca2+ influx effectively caused by UV or apoptotic stress. Together, membrane WWOX/TβRII complex is needed for cell-to-cell recognition, maintaining the efficacy of Ca2+ influx, and control of cell invasiveness., Yu-An Chen et al characterize the role of cell surface epitopes of the tumor suppressor protein WWOX in cell–cell recognition. The find that cells expressing functional WWOX, repel cancer cells which express dysfunctional WWOX or lack this protein, in a manner mediated by WWOX epitope 286-299.

Proapoptotic tumor suppressor WWOX is upregulated in the early stage of cancer initiation, which probably provides limitation to cancer growth and progression. Later, WWOX protein is reduced to enhance cancer cell growth, migration, invasiveness and metastasis. To understand how WWOX works in controlling cancer progression, here we demonstrate that apoptotic stress mediated by ectopic WWOX stimulated cancer cells to secrete basic fibroblast growth factor (bFGF) in order to support capillary microtubule formation. This event may occur in the cancer initiation stage. Later, when WWOX loss occurs in cancer cells, hyaluronidase production is then increased in the cancer cells to facilitate metastasis. We determined that inhibition of membrane hyaluronidase Tyr216-phosphorylated Hyal-2 by antibody suppresses cancer growth in vivo. WWOX-negative (WWOX-) cells dodged WWOX+cells in the microenvironment by migrating individually backward to avoid physical contacts and yet significantly upregulating the redox activity of WWOX+parental cells or other WWOX+cell types for causing apoptosis. Upon detecting the presence of WWOX+cells from a distance, WWOX- cells exhibit activation of MIF, Hyal-2, Eph, and Wnt pathways, which converges to MEK/ERK signaling and enables WWOX- cells to evade WWOX+cells. Inhibition of each pathway by antibody or specific chemicals enables WWOX- cells to merge with WWOX+cells. In addition, exogenous TGF-β assists WWOX- cells to migrate collectively forward and merge with WWOX+cells. Metastatic WWOX- cancer cells frequently secrete high levels of TGF-β, which conceivably assists them to merge with WWOX+cells in target organs and secure a new home base in the WWOX+microenvironment. Together, loss of WWOX allows cancer cells to develop strategies to dodge, compromise and even kill WWOX-positive cells in microenvironment.

Background Production of medicinal plants in Taiwan is not only hampered by international market competition, but also lack of knowledge of their pathogens, such as powdery mildew fungi (Erysiphales, Ascomycota). Records of these fungi in Taiwan originate from few researchers for the last one hundred years and are still incomplete. Since powdery mildews in tropical/subtropical environments rarely develop the sexual stages with morphologically diagnostic characteristics, internal transcribed spacer sequences (ITS) of the ribosomal RNA genes obtained from the asexual stages have become important modern tools for species identification. Results Powdery mildews on medicinal plants from educational and ornamental plantations in Taiwan were identified based on the anamorph morphology and ITS sequences. Four powdery mildews on medicinal plants are new records for Taiwan, Arthrocladiella mougeotii on Lycium chinense, Erysiphe glycines on Pueraria lobata, Erysiphe lespedezae on Bauhinia sp., Desmodium caudatum, and Uraria crinita, and E. lonicerae on Lonicera japonica. Eryngium foetidum is a new host for Erysiphe heraclei hitherto known on other host plants in Taiwan. Eryngium foetidum and Uraria crinita are new host plants for powdery mildews worldwide. Only specific field collection of the pathogens yielded the new records, not checking plant specimens in a phanerogam herbarium. The pathogens did not cause death of the host plants, but appeared to enhance stress by infection of mature leaves. Conclusions Taxonomic study of powdery mildews in Taiwan results into new host records of economically important medicinal plants in Taiwan with potential consequences for plant production and quarantine and also shows that host records are quite incomplete worldwide. Although ITS sequences were useful for species identification, the lack of data for several species on the same host genus on the one hand and the low variation between closely related species on the other indicate the need for further study.

Background Production of medicinal plants in Taiwan is not only hampered by international market competition, but also lack of knowledge of their pathogens, such as powdery mildew fungi (Erysiphales, Ascomycota). Records of these fungi in Taiwan originate from few researchers for the last one hundred years and are still incomplete. Since powdery mildews in tropical/subtropical environments do not develop the sexual stages with morphologically diagnostic characteristics, internal transcribed spacer sequences (ITS) of the ribosomal RNA genes obtained from the asexual stages have become important modern tools for species identification. Results Powdery mildews on four medicinal plants from educational and ornamental plantations in Taiwan were identified based on the anamorph morphology and ITS sequences. Three powdery mildews on medicinal plants are new records for Taiwan, Arthrocladiella mougeotii on Lycium chinense, Erysiphe lespedezae on Uraria crinita, and E. lonicerae on Lonicera japonica. Eryngium foetidum is a new host for Erysiphe heraclei hitherto known on other host plants in Taiwan. Eryngium foetidum and Uraria crinita are new host plants for powdery mildews worldwide. Only specific field collection of the pathogens yielded the new records, not checking plant specimens in a phanerogam herbarium. The pathogens did not cause death of the host plants, but appeared to enhance stress by infection of mature leaves. Conclusions Taxonomic study of powdery mildews in Taiwan results into new host records of economically important medicinal plants in Taiwan with potential consequences for plant production and quarantine and also shows that host records are quite incomplete worldwide. Although ITS sequences were useful for species identification, the lack of data for several species on the same host genus on the one hand and the low variation between closely related species on the other indicate the need for further study.

Background/Aim: Ursolic acid (UA), a triterpene compound present in natural plants, has been shown to induce cytotoxic effects on many human cancer cells through induction of cell-cycle arrest and apoptosis. This study investigated the effects of UA on human lung cancer NCI-H292 cells in vitro. Materials and Methods: Flow cytometric assay was used to measure the percentage of cell viability, apoptotic cell death by double staining of annexin V and propidium iodide (PI), production of reactive oxygen species (ROS) and Ca(2+), and mitochondriaI membrane potential (Ψ(m)). UA-induced chromatin condensation and DNA fragmentation were examined by 4’,6-diamidino-2-phenylindole staining and DNA gel electrophoresis, respectively. Western blotting was used to examine the changes of apoptosis-associated protein expression in NCI-H292 cells. Results: UA reduced cell viability and induced apoptotic cell death. UA increased Ca(2+) production, reduced Ψ(m), but did not affect ROS production in NCI-H292 cells. UA increased apoptosis-inducing factor (AIF) and endonuclease G in NCI-H292 cells. Conclusion: Based on these observations, we suggest UA induces apoptotic cell death via AIF and Endo G release through a mitochondria-dependent pathway in NCI-H292 cells.

Background/aim Laminarin, mainly found in the fronds of Laminaria, has antimicrobial characteristics and induces immune responses. However, there are no available information to show the laminarin effect on glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels in mice with leukemia in vivo. Materials and methods Fifty normal BALB/c mice were separated randomly into five groups. Group I mice received normal diet as control. Leukemia was generated in groups II-V using WEHI-3 cells: Group II mice received normal diet as positive control; group III, IV and V mice received laminarin at 1, 2.5 and 5 mg/ml with ddH2O, respectively, by oral gavage every 2 days for 14 days (total of seven times). All mice were weighed during the treatment. After treatment, mice were sacrificed, blood was collected for determination of cell markers, liver and spleen samples were weighed, and spleens were used for phagocytosis and natural killer (NK) cell activity and cell proliferation using flow cytometric assay. Results Laminarin did not affect animal appearances, but increased the body weight at all doses. It reduced the weight of liver at 2.5 and 5 mg/ml and of spleen at 5 mg/ml. Laminarin increased CD3 (2.5 mg/ml) and CD19 (1 and 5 mg/ml) cell populations but reduced CD11b (5 mg/ml) cell populations, however, these did not affect Mac-3 marker level. Laminarin at 1 mg/ml increased phagocytosis by macrophages from peripheral blood mononuclear cell, but did not affect those from the peritoneal cavity. Laminarin increased NK cell cytotoxic activity at all doses and at a target ratio of 25:1 and 50:1. Laminarin did not affect B-cell proliferation, but at 5 mg/ml significantly reduced T-cell proliferation. Laminarin restored glutamate oxaloacetate transaminase (2.5 and 5 mg/ml) and glutamate pyruvate transaminase (2.5 mg/ml) levels. Based on these results, we suggest that laminarin can promote immune responses and protect against liver injury.

Objective: Pelvic endometriosis was found to be associated with oxidative stress in the peritoneal cavity. Endogenous melatonin was known for its antioxidative activities, and oral melatonin had been studied as a treatment option for endometriosis. However, the association between endogenous melatonin and endometriosis has not yet been determined. Materials and methods: A cross-sectional case-control study was implemented. Blood and urine samples from women with surgically confirmed ovarian endometriomas, benign adnexal tumors other than endometriomas, and healthy volunteers were collected and tested for cancer antigen 125 (CA125) as well as urinary 6-sulfatoxymelatonin (aMT6s), a surrogate for average serum melatonin level. Results: A total of 97 patients with endometriomas, 59 with benign ovarian tumors other than endometriomas, and 80 women without adnexal lesion were recruited. Elevated serum CA125 and decreased body mass index were found in patients with ovarian endometriosis (both p

Three-dimensional transvaginal ultrasonography was used to diagnose a septate uterus in a 24-year-old woman with infertility for 2 years. On infertility workup, semen analysis of her husband also revealed oligoasthenoteratospermia. Hysteroscopic metroplasty was performed successfully to resolve the uterine septum; however, subsequent in vitro fertilization and intracytoplasmic sperm injection yielded a blighted ovum requiring dilatation and curettage. After curettage, the patient had hypomenorrhea secondary to intrauterine synechiae and was treated with a hysteroscopic resectoscope and lysis of adhesions. Following these procedures, assisted reproductive technology was again implemented and resulted in a successful pregnancy. In our experience, three-dimensional transvaginal ultrasonography is a noninvasive, accurate, and easy method for the diagnosis of Mullerian duct anomalies, including septate uterus. Hysteroscopic metroplasty helps to normalize intrauterine cavity architecture. Additionally, it is important to repeat hysteroscopic examination when intrauterine adhesions are highly suspected.

Objective The aim of this case-control study was to investigate whether the vitamin D receptor ( VDR ) 1a promoter gene polymorphisms are associated with susceptibility to polycystic ovary syndrome (PCOS). Methods Women with PCOS and a control group, all aged 18–45 years, were enrolled. Genotypes of two functional single nucleotide polymorphisms (SNPs), the 1521 bp (G/C) and 1012 bp (A/G), located on the 1a promoter of the VDR gene were determined by using direct sequencing. Serum 25-hydroxyvitamin D levels were measured by ELISA. Results Two functional SNPs in the 1a promoter region of the VDR gene were in complete linkage disequilibrium. The genotype distributions of these two polymorphisms in the PCOS group were not significantly different from those of the control group. Further subgroup analyses according to body mass index also revealed no significant differences in the genotype distribution in the PCOS group. Significantly lower serum 25-hydroxyvitamin D levels were observed in the heterozygous 1521CG/1012GA haplotype of both groups. Metformin treatment was only effective to increase serum 25-hydroxyvitamin D levels in PCOS patients carrying the homozygous 1521G/1012A haplotype. Conclusion These results suggest that the VDR 1a promoter polymorphisms may not be associated with the risk for PCOS, but are associated with serum 25-hydroxyvitamin D levels. Metformin treatment will be beneficial to PCOS patients without the VDR 1a promoter variant in Taiwanese population.

Objective This retrospective study aimed to investigate the use of an oxytocin antagonist in improving the pregnancy outcome of in vitro fertilization–embryo transfer (IVF–ET) in patients with repeated implantation failure (RIF). Materials and Methods A total of 150 infertile couples with RIF undergoing IVF–ET were divided into three groups. Patients who did not receive atosiban were used as controls (Group 1; n =80). Forty patients received a single bolus dose (6.75mg, 0.9mL/vial) of atosiban before ET (Group 2), and 30 patients received a bolus dose of 6.75mg atosiban followed by infusion at 18mg/hr for 3 hours immediately after ET (Group 3). Results A significantly higher implantation rate (30.21%) was noted in Group 2 compared with Groups 1 and 3 (11.8% and 15.9%, respectively; p =0.0006). The clinical pregnancy rate of Group 2 (37.5%) was significantly higher than that of Groups 1 (12.5%) and 3 (20%) ( p =0.0057). The live birth rate was significantly higher in Group 2 (35%) than in Groups 1 and 3 (10% and 16.67%, respectively; p =0.0031). Conclusion These results suggest that IVF–ET using lower dosage of atosiban may improve pregnancy outcomes of patients with RIF.

Monosomy 9p syndrome, also known as Alfi syndrome, has been described as a contiguous syndrome characterized by mental retardation, developmental delay, and facial dysmorphisms. Males with monosomy 9p often express variable degrees of feminization, although the genitalia of females will be normal. In the present report, we describe a case of ambiguous genitalia and intra-abdominal testicular development, with a derivative chromosome 9 arising from a translocation between 9p23 and Yq heterochromatin. Pathologic examination of the testes showed germ cell hypoplasia of the seminiferous tubules. fluorescence in situ hybridization, spectral karyotyping, and array comparative genomic hybridization were used to characterize the genetic changes.

More than half of people with Parkinson's disease (PwPD) report difficulty when turning, which has significant implications for their risk of falling. Turn steps, turn time, turn type, and turn quality are key elements that could be observed in a video-based clinical assessment. This assessment could be carried out at home with video cameras that are simple to operate and easy to obtain. A laboratory-based examination investigates quantitative and kinematic data, such as the onset time of the head, trunk, pelvis, and leg, and the amplitude of angular rotation and relative rotation angles between different segments of the body in both the roll and yaw planes. PwPD take more steps, have a longer turn time, and use less efficient turn types, such as delayed onset, incremental, and larger turning-arc turn types, to complete a turn than unaffected individuals. They display instability, use of support, lack of ground clearance and lack of continuity during a turn. Poor intersegmental coordination and slower and smaller rotations of the head, trunk, and pelvis are also observed in turning. Increased postural tone, axial rigidity and loss of intersegmental flexibility may contribute to an en bloc turning strategy. Impaired motor planning, bradykinesia, and freezing make it difficult for PwPD to switch from one motor program (turning) to another (walking). Clinicians should examine patients' turning capacity during a routine movement evaluation and note any complaints about difficulties in turning. Testing of turning tasks needs to be done on both sides and related to real-life experience. Therapists should assist PwPD to find adaptive strategies, such as home modification and compensatory strategies while turning. Rehabilitation programs should focus on enhancing balance training and axial mobility.

Malignant breast cancer MDA-MB-231 cells are highly metastatic and their cell-cell contact is fairly loose. Accordingly, they migrate individually. Upon stably expressing with ERK, the MDA-MB-231 cells lost individual migration and underwent migration in a collective manner. No apparent loss of speed was observed due to ectopic ERK. Suppression of ERK phosphorylation by U0126 abolished ERK-induced collective migration. Similarly, dominant negative ERK with K72R mutation failed to induce collective migration, indicating that ERK phosphorylation is needed for its induction of collective migration. MDA-MB-231 is a WWOX-negative cell line due to epigenetic modification in the promoter. Ectopic ERK induced the expression of endogenous WWOX. Stimulation of cells with antibody against Ser14 phosphorylation in WWOX abolished the ERK-induced collective migration. In parallel, transiently overexpressed WWOX increased cell-to-cell adhesion and their collective migration. These observations suggest that ERK-induced c...

// Ming-Hui Lee 1, * , Wan-Pei Su 1, * , Wan-Jen Wang 1, * , Sing-Ru Lin 1, * , Chen-Yu Lu 1, * , Yu-An Chen 1, * , Jean-Yun Chang 1 , Shenq-Shyang Huang 1 , Pei-Yi Chou 1 , Siou-Ru Ye 1 , Szu-Jung Chen 1 , Huan He 1 , Ting-Hsiu Liu 1 , Ying-Tsen Chou 2 , Li-Jin Hsu 3, 4, * , Feng-Jie Lai 5 , Shean-Jen Chen 6 , Hoong-Chien Lee 7 , David Kakhniashvili 8 , Steven R. Goodman 8 , Nan-Shan Chang 1, 2, 4, 6, 9 1 Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan, ROC 2 Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan, Taiwan, ROC 3 Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University Medical College, Tainan, Taiwan, ROC 4 Center of Infectious Disease and Signal Research, National Cheng Kung University, Tainan, Taiwan, ROC 5 Department of Dermatology, Chi-Mei Medical Center, Tainan, Taiwan, ROC 6 Advanced Optoelectronic Technology Center, National Cheng Kung University Medical College, Tainan, Taiwan, ROC 7 Graduate Institute of Systems Biology and Bioinformatics, National Central University, Zhongli, Taiwan, ROC 8 Institute of Biomedical Sciences and Technology, Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, NY, USA 9 Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA * These authors have contributed equally to this work Correspondence to: Nan-Shan Chang, e-mail: nschang13827@gmail.com Keywords: Zfra, skin cancer, melanoma, metastasis, stemness Received: September 18, 2014 Accepted: December 11, 2014 Published: February 20, 2015 ABSTRACT Zfra is a 31-amino-acid zinc finger-like protein, which participates in the tumor necrosis factor signaling. Here, we determined that when nude mice and BALB/c mice were pre-injected with nanogram levels of a synthetic Zfra1–31 or truncated Zfra4–10 peptide via tail veins, these mice became resistant to the growth, metastasis and stemness of melanoma cells, and many malignant cancer cells. The synthetic peptides underwent self-polymerization in phosphate-buffered saline. Alteration of the Ser8 phosphorylation site to Gly8 abolished Zfra aggregation and its-mediated cancer suppression in vivo . Injected Zfra peptide autofluoresced due to polymerization and was trapped mainly in the spleen. Transfer of Zfra-stimulated spleen cells to naive mice conferred resistance to cancer growth. Zfra-binding cells, designated Hyal-2+ CD3- CD19- Z cells, are approximately 25–30% in the normal spleen, but are significantly downregulated (near 0–3%) in tumor-growing mice. Zfra prevented the loss of Z cells caused by tumors. In vitro stimulation or education of naive spleen cells with Zfra allowed generation of activated Z cells to confer a memory anticancer response in naive or cancer-growing mice. In particular, Z cells are abundant in nude and NOD-SCID mice, and can be readily activated by Zfra to mount against cancer growth.

The genotoxicity of low-level exposure to ethylene dichloride (EDC) and vinyl chloride monomer (VCM) in humans is not clear. We used lymphocyte sister chromatid exchange (SCE) frequency as a parameter to investigate the genotoxicity of low level EDC and VCM in VCM-manufacturing workers. The SCE frequency was determined for 51 male workers with exposure to VCM and/or EDC and for 20 male workers devoid of such exposure. Epidemiological data were obtained by questionnaire, and included history of smoking, drinking, and any medication taken, as well as a detailed occupational history. Personal- and area-sampling and analysis were conducted in order to calculate the time-weighted average (TWA) contaminant-exposure level corresponding to different job categories. Moderate EDC exposure around 1 ppm corresponded to a significantly greater SCE frequency than was the case for the low EDC exposure group (p

Won-Pei Su1, Shu-Hui Chen2, Szu-Jung Chen1, Pei-Yi Chou1, Chun-Cheng Huang1 and Nan-Shan Chang1,3,4 1Institute of Molecular Medicine, National Cheng Kung University, Tainan, Taiwan, 2Department of Chemistry, National Cheng Kung University, Tainan, Taiwan, 3Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, 4Department of Neurochemistry, NYS Institute of Basic Research in Developmental Disabilities, Staten Island, NY, 1,2ROC 3,4USA

Recent studies have demonstrated that transforming growth factor beta (TGF-β1)-induced antiapoptotic factor (TIAF1) is able to form aggregates in the hippocampi of middle-aged normal individuals. The aggregating TIAF1 induces generation of amyloid beta (Aβ) for causing neurodegeneration. Intriguingly, TIAF1 aggregates are shown, together with Smad4 and Aβ, in the cancer stroma and peritumor capsules of many solid tumors. During lung cancer progression, for example, TIAF1 and amyloid fibrils are significantly upregulated in the cancer stroma. Aggregates of TIAF1 and Aβ are shown on the interface between metastatic lung cancer cells and the brain tissues. Conceivably, these peritumor materials are needed for cancer cells to survive. In vitro experiments revealed that TIAF1 is a crucial component for tumor suppressors p53 and WWOX-mediated tumor suppression and apoptosis. While metastatic lung cancer cells are frequently devoid of WWOX and p53, we provide new perspectives regarding the role of TIAF1 in the pathogenesis of lung cancer development, and propose a therapeutic approach for targeting TIAF1. Electronic supplementary material The online version of this article (doi:10.1186/2213-0802-1-5) contains supplementary material, which is available to authorized users.