Early detection of oral health status and cardiometabolic risk factors among reproductive-aged women in rural areas: A cross-sectional study.

BACKGROUND: Oral health status is associated with many chronic ailments, including diseases of the cardiovascular system, diabetes, as well as pregnancy complications, such as low birth weight, preterm delivery, preeclampsia, and early pregnancy loss. The health status of reproductive-aged women is important, not only for the women themselves, but also for the health of fetus. OBJECTIVES: The purpose of this study was to explore cardiometabolic risk factors, oral health status, and associated factors among reproductive-aged women. METHODS: The current study is a preliminary report from a nurse-led longitudinal study, examining a health promotion program for women in a rural region of Taiwan. Participants consisted of a community-based, cross-sectional sample, involving 2547 women aged 20-49 years. RESULTS: A high percentage of participants were found to have cardiometabolic risk factors. More than one-quarter had ⩽24 remaining teeth. Many participants reported that they did not regularly attend dental checkups and tooth scaling, did not brush at least twice a day after meals, did not have a healthy diet, and did not exercise regularly. The results also indicated that women with <20 remaining teeth tended to be older, engaged in substance use, and displayed increased cardiometabolic risk factors. CONCLUSIONS: The findings indicate that reproductive-aged women show a high prevalence of tooth loss, cardiometabolic risk factors, and unhealthy habits. Nurses in the primary health sectors could reduce the consequences of these risk factors and improve oral health through the early detection and initiation of health-promoting programs that reduce risky behavior associated with cardiometabolic diseases.

Prognostic role of excision repair cross complementing-1 and topoisomerase-1 expression in epithelial ovarian cancer.

OBJECTIVE: Epithelial ovarian cancer is the most lethal gynecologic cancer worldwide and chemoresistance is one of the major causes of treatment failure. We investigated whether ERCC1, TAU, TOPO2A, TOPO1, P53, and C-MYC expression could be used as predictors for treatment outcomes. MATERIALS AND METHODS: Immunohistochemical staining was used to examine the expression of these biomarkers in resected tumor specimens from 38 patients treated in our institute. Clinicopathological data including demographics, staging, histological type, treatment response, expression of the biomarkers, and patient outcomes were analyzed. RESULTS: The median follow-up period was 47.5 months (range, 10-135 months) and the median overall survival was 56.0 months. Patients who did not have expression of ERCC1, and those who had expression of TOPO1 had significantly better overall survival. Cox regression analysis also confirmed that these two biomarkers were significant independent factors predicting survival (ERCC1, hazard ratio 5.51, 95% confidence interval: 2.02-14.00, p = 0.001; TOPO1, hazard ratio 0.22, 95% confidence interval: 0.06-0.77, p = 0.017). CONCLUSION: We concluded that poor overall survival was significantly associated with positive ERCC1 and negative TOPO1 expression. The results might be the consequence of chemoresistance to platinum and camptothecins, both of which are commonly used regimens in the treatment of epithelial ovarian cancer.

MicroRNA-27b Enhances the Hepatic Regenerative Properties of Adipose-Derived Mesenchymal Stem Cells.

Adipose-derived mesenchymal stem cells (ASCs) are readily available multipotent mesenchymal progenitor cells and have become an attractive therapeutic tool for regenerative medicine. We herein investigated the mechanistic role of how miR-27b modulated regenerative capacities of ASCs. Intravenous administration of miR-27b-transfected ASCs (ASCs-miR-27b) was conducted after 70% partial hepatectomy (PH). After PH, rats injected with ASCs-miR-27b had decreased inflammatory cytokines and increased hepatocyte growth factor and other related growth factors. We showed that the nature of ASCs-miR-27b to inhibit hepatic stellate cell activation was dependent upon peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) in vitro. Moreover, expression of miR-27b in ASCs induced heme oxygenase-1 (HO-1), resulting in increased production of ATP, protective cytokines/growth factors, and genes involved in mitochondrial biogenesis in a PGC-1α-dependent manner. RNA sequencing (RNA-Seq) analysis revealed drastic transcriptional changes in livers treated with ASCs-miR-27b after PH. The differentially expressed genes classified into "regeneration," "fibrosis," and "mitochondrial biogenesis" clusters were mainly mitochondrial. The potential biological context reflecting the effects of PGC-1α by ASCs-miR-27b treatment was also observed by the subnetwork analysis with HO-1 and PGC-1α being the top-ranked regulatory genes. We demonstrate autologous ASCs-miR-27b enhances liver regeneration and, importantly, preserves hepatic function through paracrine actions which offers a viable therapeutic option to facilitate rapid recovery after liver injury.

Identification of miR-27b as a novel signature from the mRNA profiles of adipose-derived mesenchymal stem cells involved in the tolerogenic response.

Adipose-derived mesenchymal stem cells (adipose-derived MSCs, ASCs) possess the ability to differentiate into multiple tissue types and have immune-modulatory properties similar to those of MSCs from other origins. However, the regulation of the MSC-elicited immune-modulatory activity by specific microRNA (miRNA) mechanisms remains unexplored. Gene expression profiling with knowledge-based functional enrichment analysis is an appropriate approach for unraveling these mechanisms. This tool can be used to examine the transcripts and miRNA regulators that differentiate the rat tolerogenic orthotopic liver transplantation (OLT; DA liver into PVG) and rejection OLT (DA liver into LEW) models. In both models, the rejection reaction was observed on postoperative day 7∼14 (rejection phase) but was overcome only by the PVG recipients. Thus, the global gene expression patterns of ASCs from spontaneously tolerant (PVG) and acute rejecting (LEW) rats in response to LPS activation were compared. In this study, we performed miRNA enrichment analysis based on the analysis of pathway, gene ontology (GO) terms and transcription factor binding site (TFBS) motif annotations. We found that the top candidate, miR-27, was specifically enriched and had the highest predicted frequency. We also identified a greater than 3-fold increase of miR-27b expression in the ASCs of tolerant recipients (DA to PVG) compared to those of rejecting recipients (DA to LEW) during the rejection phase in the rat OLT model. Furthermore, our data showed that miR-27b knockdown has a positive influence on the allosuppressive activity that inhibits T-cell proliferation. We found that miR-27 knockdown significantly induced the expression of CXCL12 in cultured ASCs and the expression of CXCL12 was responsible for the miR-27b antagomir-mediated inhibition of T-cell proliferation. These results, which through a series of comprehensive miRNA enrichment analyses, might be relevant for stem cell-based therapeutic applications in immunosuppressive function using ASCs.

Identification of the deleted in split hand/split foot 1 protein as a novel biomarker for human cervical cancer.

The morphological detection of early neoplastic transformation leading to cervical cancer remains problematic. In this work, we have identified deleted in split hand/split foot 1 protein (DSS1) as an early biomarker that is specifically upregulated in premalignant and malignant cervical epithelial cells, but is low or undetectable in non-malignant cells. DSS1 mRNA and protein levels are significantly increased in cultured human cervical carcinoma cell lines originating from primary and metastatic tumors. In fact, > 96% of patient tumor tissues were found to have cells with elevated DSS1 when compared with tumor-adjacent normal cells. In histological sections of cervical tissue containing either invasive cervical carcinoma or its precursor lesions, DSS1 was readily detected in the tumor cells. Steady-state DSS1 expression by immortalized cervical cancer cell lines was found to be necessary for maintenance of their transformed phenotype, since stable shRNA-mediated depletion of DSS1 in HeLa cells inhibited their proliferation and colony-forming activity in monolayer cultures and prevented division of these cells in soft agar. When DSS1 levels are reduced using shRNA, the cells ultimately undergo apoptosis via activation of p53 and the p53 downstream targets, and cleavage of apoptosis-associated proteins including CPP32/caspase-3, poly(ADP-ribose)polymerase and DNA-PKcs. In addition, silencing of DSS1 makes cervical cancer cells sensitive to cell death after treatment with cisplatin. We conclude that the DSS1 protein is critically involved in the maintenance of the transformed phenotype in cervical cancer cells, and that it might be a specific, robust and reliable marker for early detection, diagnosis and treatment.

High immunohistochemical expression of TGF-ß1 predicts a poor prognosis in cervical cancer patients who harbor enriched endoglin microvessel density.

Endoglin, a coreceptor for transforming growth factor ß1 (TGF-ß1) in vascular endothelial cells, is highly upregulated in tumor vessels and therefore is a specific biomarker for angiogenesis. Some studies have suggested that assessment of tumor angiogenesis may predict cancer response to chemotherapy and radiotherapy. In this study, we attempted to analyze the immunohistochemical expression of endoglin and TGF-ß1 from 80 patients with different International Federation of Gynecology and Obstetrics (FIGO) stages of cervical cancer before they received concurrent chemoradiation and to investigate their prognostic significance. The median follow-up period was 86 months (range, 2-144 months). Endoglin staining was assessed by microvessel density (MVD), whereas TGF-ß1 expression was semiquantified as negative, weakly, or strongly staining. A receiver operating characteristic curve was established for endoglin MVD in predicting survival; the optimal cutoff value was 11.125. With a Cox regression analysis, we found that an advanced FIGO stage (hazard ratio 4.66; 95% confidence interval 2.10-10.32, P<0.001) and endoglin MVD more than 11.125 (hazard ratio 12.21; 95% confidence interval 3.62-41.16, P=<0.001) were independent factors to predict survival. Interestingly, a strong TGF-ß1 expression was significantly associated with poor survival only when the endoglin MVD value was higher than 10. Our study shows that evaluation of endoglin MVD by immunochemistry can be used as an independent prognostic marker for cervical cancer patients receiving concurrent chemoradiation. TGF-ß1 also had an impact on survival only when endoglin MVD was enriched, suggesting its involvement in tumor progression in the later stage of angiogenesis.

Epidemiology of group B Streptococcus ST-17 clone in pregnant women of South Taiwan.

OBJECTIVES: We aimed to utilize a simple molecular assay to simultaneously detect both group B Streptococcus (GBS) and virulent ST-17 rectovaginal colonization. We also attempted to estimate the prevalence of maternal GBS and ST-17 carriers and to evaluate their seasonal association. SUBJECTS AND METHODS: We used an optimized multiplex PCR method employing scp-B and ST-17 primers to analyze DNA extracted from rectovaginal swabs of 3,064 cases collected over 3 years. The incidence trends, seasonal variations, and temperature preference were analyzed. RESULTS: The overall prevalence of maternal colonization for GBS and ST-17 clone were 13.25 and 2.48%, respectively. The ST-17 to GBS ratio was 18.72%. The occurrence of ST-17 colonization was significantly associated with seasonal variations with a preference for lower temperatures. CONCLUSIONS: We developed a novel multiplex PCR method suitable for the simultaneous detection of GBS and ST-17 clone. The phenomenon of lower temperature preference for ST-17 clone necessitates further investigation. The epidemiological data for GBS and ST-17 incidence are especially important to establish a public policy for universal GBS screening in the future.

Low-dose LBH589 increases the sensitivity of cisplatin to cisplatin-resistant ovarian cancer cells.

OBJECTIVE: There is a need to develop alternative therapeutic strategies to overcome cisplatin-associated resistance in patients with ovarian cancer. Histone deacetylation (HDAC) associated with inactivation of genes has been implicated in the epigenetic silencing of tumor suppressor genes affecting critical biological activities in cancer cells and may be an important factor in acquired cisplatin-associated resistance. In this report, we tested a combination of cisplatin and LBH589 (histone deacetylation inhibitor) in cisplatin-resistant ovarian cancer cells to explore the reversal effect of cisplatin resistance and changes of gene expression. MATERIALS AND METHODS: To detect the synergistic effects of antiproliferation between cisplatin and LBH589 in ovarian cancer cells, we performed a cell viability assay and a clonogenic assay. To investigate the differences of gene expression between cells treated by cisplatin alone and cotreated with cisplatin and LBH589, a microarray mRNA analysis was performed. RESULTS: In the presence of low-dose LBH589, the inhibition concentration value of cisplatin for A2780-cp70 cells was much lower than with cisplatin treatment alone. Gene expression profiles identified that a total of 354 genes had been significantly upregulated and a total of 63 genes been downregulated with LBH589 cotreatment. CONCLUSION: We hypothesized that combination of cisplatin and LBH589 can override cisplatin-associated resistance in ovarian cancer cells. These results provide initial evidence for testing this combination in clinical use.

Prognostic value of pretreatment carcinoembryonic antigen after definitive radiotherapy with or without concurrent chemotherapy for squamous cell carcinoma of the uterine cervix.

PURPOSE: To evaluate whether pretreatment carcinoembryonic antigen (CEA) levels have a prognostic role in patients after definitive radiotherapy for squamous cell carcinoma (SCC) of the uterine cervix. METHODS AND MATERIALS: A retrospective study of 550 patients was performed. The SCC antigen (SCC-Ag) and CEA levels were regarded as elevated when they were ≥2 and ≥5 ng/mL, respectively. A total of 208 patients underwent concurrent chemoradiotherapy (CCRT). The Kaplan-Meier method was used to calculate the distant metastasis (DM), local failure (LF), disease-free survival (DFS), and overall survival (OS) rates. Multivariate analysis was performed using the Cox proportional hazards model. The hazard ratio (HR) with 95% confidence interval (CI) was evaluated for the risk of a poor prognosis. RESULTS: Compared with the patients with normal CEA/SCC-Ag levels, CEA levels ≥10 ng/mL but without elevated SCC-Ag levels was an independent factor for LF (HR, 51.81; 95% CI, 11.51-233.23; p < .001), DM (HR, 6.04; 95% CI, 1.58-23.01; p = .008), DFS (HR, 10.17; 95% CI, 3.18-32.56; p < .001), and OS (HR, 5.75; 95% CI, 1.82-18.18; p = .003) after RT alone. However, no significant role for CEA was noted in patients with SCC-Ag levels ≥2 ng/mL. In patients undergoing CCRT, a CEA level ≥10 ng/mL was an independent factor for LF (HR, 2.50; 95% CI, 1.01-6.21; p = .047), DM (HR, 3.41; 95% CI, 1.56-7.46; p = .002), DFS (HR, 2.73; 95% CI, 1.39-5.36; p = .003), and OS (HR, 3.93; 95% CI 1.99-7.75; p < .001). A SCC-Ag level of ≥40 ng/mL was another prognostic factor for DM, DFS, and OS in patients undergoing not only CCRT, but also RT alone. The 5-year OS rate for CCRT patients with CEA <10 ng/mL and ≥10 ng/mL was 75.3% and 35.8%, respectively (p < .001). CCRT was an independent factor for better OS (HR, 0.69; 95% CI, 0.50-0.97; p = .034). CONCLUSION: Pretreatment CEA levels in patients with SCC of the uterine cervix provide complementary information for predicting LF, DM, DFS, and OS, except for in patients with abnormal SCC-Ag levels before RT alone. More aggressive therapy might be advisable for patients with CEA levels of ≥10 ng/mL.

High prevalence of genital human papillomavirus type 52 and 58 infection in women attending gynecologic practitioners in South Taiwan.

BACKGROUND: We attempted to determine the prevalence of genital human papillomavirus (HPV) infection in women attending gynecologic practitioners in South Taiwan. METHODS: The population included 4383 women aged 16-78 seeking HPV testing at primary gynecologic practitioners regardless of their cervical cytology results. HPV DNA was identified from cervical swabs using semi-nested polymerase chain reaction with MY11, MY09/HMB01, and MY11/bioGP6+ primers. Genotyping for high-risk HPV (HR-HPV) was done separately by a HR-HPV chip, which contained 13 type-specific oligonucleotides on a nylon membrane. RESULTS: The overall HPV prevalence was 19.3% (849/4383), 11.1% (488/4383) were confirmed as HR-HPV positive. Among the women with HR-HPV infection, HPV-16 was the most prevalent type (22.1%; 108/488), followed by HPV-52 (21.3%; 104/488), and HPV-58 (19.9%; 97/488). Multiple infections were detected in 73 women (15.0%; 73/488). For women with age 30 or younger, the overall HPV and HR-HPV prevalence were 32.0% and 20.7%, respectively, which were significantly higher than those of women age older than 30 (17.2% and 9.5%, P < 0.001). More multiple infections (22.1% vs. 12.4%) were also found in women with age 30 or younger (P = 0.021). However, the relative contribution of types to the overall HR-HPV positive among different age groups remains the same. CONCLUSIONS: Our results showed an HPV prevalence that is similar compared with worldwide levels. HPV prevalence and multiple infections rate were decreasing across the age groups. Unlike most previous studies, the relative high prevalence of HPV 52 and 58 among South Taiwan women has important implications in vaccine prophylaxis.

A simple method for the detection and genotyping of high-risk human papillomavirus using seminested polymerase chain reaction and reverse hybridization.

BACKGROUND: To develop a simple and cost-effective method for the detection and genotyping of high-risk human papillomaviruses (HPV) using seminested polymerase chain reaction (PCR) and reverse hybridization. METHODS: Cervical swabs for HPV testing were collected from 127 women with normal cervical cytology and 57 patients with cervical lesions of various degrees. After DNA isolation, PCR amplification was first carried out using MY11 and MY09/HMB01 primers, then labeled by seminested PCR using the first PCR products and MY11/bioGP6+ primers. One fifth of the second PCR products were resolved by gel electrophoresis. Genotyping for high-risk HPV was done separately, using the remaining products, by a high-risk HPV chip, which contained 13 type-specific oligonucleotides on a nylon membrane. The final result was detected by colorimetric change on the chip under direct visualization. RESULTS: High-risk HPV DNA was detected in 19 (15%) of 127 women with normal cervical smear cytology, in 26 (89.7%) of 29 patients with cervical intraepithelial neoplasia (CIN), and in 27 (96.4%) of 28 patients with invasive cervical carcinoma. Multiple high-risk HPV infections were detected in five cases. HPV type 16 was the most frequent type of infection, comprising 34.5% and 53.6% of the patients with CIN and invasive carcinoma, respectively. The samples without a visible 190-bp band on electrophoresis exclusively showed negative hybridization results. This method could detect one to two copies of the HPV-16 genome derived from one SiHa cell. The overall sensitivity of HPV detection was 25 to 50 copies of HPV genome for each specimen. Thirteen high-risk types and twenty-four different types of HPV DNA showed specific hybridization without any cross-reaction. CONCLUSIONS: Our results demonstrated the feasibility and optimistic prospects for this simple and cheap method of high-risk HPV genotyping. This technology can be easily set up in a routine molecular laboratory and would probably be of great value in cervical cancer prevention programs.