Titanium Surfaces with a Laser-Produced Microchannel Structure Enhance Pre-Osteoblast Proliferation, Maturation, and Extracellular Mineralization In Vitro.

The clinical success of dental titanium implants is profoundly linked to implant stability and osseointegration, which comprises pre-osteoblast proliferation, osteogenic differentiation, and extracellular mineralization. Because of the bio-inert nature of titanium, surface processing using subtractive or additive methods enhances osseointegration ability but limits the benefit due to accompanying surface contamination. By contrast, laser processing methods increase the roughness of the implant surface without contamination. However, the effects of laser-mediated distinct surface structures on the osteointegration level of osteoblasts are controversial. The role of a titanium surface with a laser-mediated microchannel structure in pre-osteoblast maturation remains unclear. This study aimed to elucidate the effect of laser-produced microchannels on pre-osteoblast maturation. Pre-osteoblast human embryonic palatal mesenchymal cells were seeded on a titanium plate treated with grinding (G), sandblasting with large grit and acid etching (SLA), or laser irradiation (L) for 3-18 days. The proliferation and morphology of pre-osteoblasts were evaluated using a Trypan Blue dye exclusion test and fluorescence microscopy. The mRNA expression, protein expression, and protein secretion of osteogenic differentiation markers in pre-osteoblasts were evaluated using reverse transcriptase quantitative polymerase chain reaction, a Western blot assay, and a multiplex assay, respectively. The extracellular calcium precipitation of pre-osteoblast was measured using Alizarin red S staining. Compared to G- and SLA-treated titanium surfaces, the laser-produced microchannel surfaces enhanced pre-osteoblast proliferation, the expression/secretion of osteogenic differentiation markers, and extracellular calcium precipitation. Laser-treated titanium implants may enhance the pre-osteoblast maturation process and provide extra benefits in clinical application.

Trends and Age-Period-Cohort Effect on Incidence of Male Breast Cancer from 1980 to 2019 in Taiwan and the USA.

Although male breast cancer (MBC) is globally rare, its incidence significantly increased from 1990 to 2017. The aim of this study was to examine variations in the trends of MBC incidence between populations in Taiwan and the USA from 1980 to 2019. The Taiwan Cancer Registry database and the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute of the USA were used. The age-standardized incidence rate was calculated using the world standard population in 2000. The long-term trends of the age, time period, and birth cohort effect on MBC incidence rates were estimated using the SEER Age-Period-Cohort Web Tool. The results revealed that the incidence of MBC in both countries increased from 2010 to 2019 (Taiwan: average annual percentage change (AAPC) = 2.59%; USA: AAPC = 0.64%). The age and period effects on the incidence rates in both countries strengthened, but the cohort effect was only identified in Taiwan (Rate ratio: 4.03). The identified cohort effect in this study bears resemblance to that noted in a previous investigation on female breast cancer in Taiwan. This suggests the possible presence of common environmental factors influencing breast cancer incidence in both genders, such as a high fat diet and xenoestrogen.

Efficacy of Er:YAG laser for the peri-implantitis treatment and microbiological changes: a randomized controlled trial.

The aims of this study were to identify the microbiological changes in the periodontal pockets following an Er:YAG laser (ERL) irradiation and mechanical debridement to compare the effectiveness of ERL irradiation to mechanical debridement for peri-implantitis treatment through randomized controlled trials. Twenty-three patients with peri-implantitis lesions were treated in either a test group, ERL set at energy level of 100 mJ/pulse, frequency of 10 Hz, pulse duration was 100 µs, and irradiated by three passages, or a control group, with mechanical debridement using an ultrasonic scaler. An examiner measured the following clinical parameters at different stages (a baseline and at 3- and 6-month post-treatment): probing depth (PD), bleeding on probing (BOP), marginal bone loss (MBL), and anaerobic bacteria counts. Linear regression, with generalized estimation equations, was used to compare the clinical parameters and anaerobic bacterial counts at different stages and between groups. The anaerobic bacterial counts significantly decreased within the control group during the follow-ups. At the 6-month follow-up, both groups showed a significant reduction in PD (test group: mean difference of 0.84 mm; control group: mean difference of 0.41 mm), and the test group showed a significantly higher PD reduction on the buccal site (1.31 mm) compared to that of the control group (0.25 mm). Both ERL and mechanical debridement treatments led to significant improvements in PD. When mechanical debridement therapy was used, significant anaerobic bacterial count reductions were observed. Future treatment of peri-implantitis should involve a combination of both of these therapies.

Knowledge of and Barriers to Palliative Care Perceived by Healthcare Providers before and after Promotion of the Patient Autonomy Act: A Cross-Sectional Study.

This study was designed to investigate healthcare providers' knowledge of palliative care and perceptions of palliative care barriers before and after promoting the Patient Autonomy Act (PAA). A convenience sample was recruited, including 277 healthcare providers in 2013 and 222 healthcare providers in 2018. Multivariate linear regression analyses were used to identify predictors of knowledge of and perceived barriers to palliative care. A principal component analysis was carried out to identify the most appropriate factorial structure for the contents of knowledge and perceived barriers to palliative care. Three factors related to knowledge of palliative care were identified in both 2013 and 2018 data: 'policy, regulation, and promotion', 'philosophy and treatments', and 'myths and misunderstandings'. Study findings for the two periods were similar. As for barriers to providing palliative care, three factors were identified for 2013: 'quality care', 'difficulties' and 'communication', and for 2018, 'information', 'attitudes' and 'quality care' were identified. Study findings differed between the two periods. Policies can better reinforce mitigating strategies-including opportunities for education, shared decision making, and changes in institutions and care systems. Additionally, assessing barriers creates important opportunities for further research to address the most critical aspects in improving end-of-life care for patients and their families.

Exercise for Trismus Prevention in Patients with Head and Neck Cancer: A Network Meta-Analysis of Randomized Controlled Trials.

A common side effect of managing head and neck cancer is trismus, which devastates patients' quality of life. The purpose of this study was to investigate prophylactic exercise interventions for preventing trismus and difficulty in mouth opening in head and neck cancer. Five databases were searched for randomized controlled trials. Network meta-analysis was performed with risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI). This study finally included 11 randomized controlled trials (n = 805). Trismus risk in patients who received exercise with phone call follow up (E + P) was significantly lower than those received usual care (RR = 0.42; 95% CI: 0.29 to 0.61) and exercise alone (RR = 0.33; 95% CI: 0.18 to 6.22). Mouth opening in usual care was significantly lower than in the tri-integrated strategy group (MD = 15.22; 95% CI: 8.88 to 21.56). Exercise is recommended for preserving mouth opening distance in patients with head and neck cancer. Tri-integrated strategies could be an effective method for preventing trismus.

Diagnosis of Peritoneal Tuberculosis from Primary Peritoneal Cancer.

Peritoneal tuberculosis (PTB) is an uncommon extrapulmonary infection mimickng primary peritoneal cancer (PPC). We retrospectively included 23 women with PTB and 47 women with PPC treated in a medical center to study the clinical and radiological features that differentiate PTB from PPC. Body temperature above 38 °C was a unique feature of PTB (34.7% versus 0%, p < 0.001). Body Mass Index (BMI) was lower (21.9 ± 3.7 versus 25.2 ± 4.1, p = 0.003), white blood cell (WBC) count was lower (5179.6 ± 1502.2 versus 7716.2 ± 2741.8, p < 0.001), and CA-125 level was lower (508.0 ± 266.1 versus 2130.1 ± 2367.2 U/mL, p < 0.001) in PTB compared with PPC. Imaging detected more pulmonary infiltration and consolidation (52.2% versus 6.4%, p < 0.001), and less omental/mesentery changes (52% versus 83%, p < 0.001) in PTB compared with PPC. The operated patients received earlier treatment compared to patients without operation (7.9 ± 5.3 days versus 17.2 ± 11.0 days, p = 0.010). In conclusion, fever above 38 °C, lower BMI, lower WBC count, less elevated CA-125 level, and imaging of less omental involvement were features of PTB differentiated from PPC.

Salivary Pro-Inflammatory Markers and Smoking Status Influences the Treatment Effectiveness of Periodontal Disease Patients with Hypertension.

BACKGROUND: Hypertension and periodontal diseases share several risk factors. Inflammation biomarkers in saliva are related to hypertension and periodontal disease. The aim of this study was to explore the role of the salivary inflammatory biomarkers in the treatment effectiveness of patients with hypertension and periodontal disease. METHODS: This observational study enrolled 160 subjects diagnosed with periodontitis, 40 of which had a history of hypertension. All subjects had completed scaling and root planning therapeutic procedures within four weeks. The clinical periodontal parameters (i.e., bleeding on probing, plaque control record (PCR), and probing depth (PD)) were evaluated before and after the treatment. Pro-inflammatory markers were determined using a commercial kit. RESULTS: The recovery rate (PD 4-9 mm) in non-hypertensive subjects was significantly higher than in hypertensive subjects (60.47% vs. 52.60%, respectively; p = 0.04). All clinical parameters, excluding PCR, positively correlated with salivary IL-1ß at baseline and after completing treatment. Our results showed that increased salivary IL-1ß levels were positively associated with decreased PCR (ß = -27.65 and p = 0.05) and PD recovery rate (ß = -17.05 and p = 0.02) in hypertensive subjects. CONCLUSIONS: The present study sheds important light on the clinical use of salivary pro-inflammatory cytokines as valuable biomarkers for predicting the treatment effectiveness of patients suffering from hypertension and periodontitis.

Rare clinical manifestations of primary peritoneal serous carcinoma presenting as colorectal cancer: A report of two cases.

OBJECTIVE: To report two cases of for primary peritoneal serous carcinoma (PPSC) to present with gastrointestinal manifestations that mimic colorectal cancer. CASE REPORT: There were two patients with initial presentations of fatigue with iron deficiency anemia, and tenesmus with bloody stool. Tumors of the ascending colon and rectum were detected by colonofiberoscope, and pathologic reports of tumor biopsies revealed adenocarcinoma of suspected gynecologic origin. Both patients underwent optimal debulking surgery without macroscopic residual tumor, and then received adjuvant carboplatin and paclitaxel chemotherapy with bevacizumab. CONCLUSIONS: PPSC can clinically present like primary colorectal carcinoma. The differential diagnosis requires special staining of several markers for tumor tissues.

Single-port laparoscopic hysterectomy for uteri greater than 500 grams.

OBJECTIVES: To study the operative outcomes of single-port laparoscopic hysterectomy in uteri greater than 500 g, using either laparoscopic assisted vaginal hysterectomy (LAVH) or laparoscopic supracervical hysterectomy (LSH). MATERIALS AND METHODS: 78 patients were included in a single institute by a single surgeon from March, 2013 to January, 2018. RESULTS: The median uterine weight was 686.5 g. Larger uterine weight was correlated with longer operative time and greater estimated blood loss. Two types of operations were performed: LAVH (n = 55) or LSH (n = 23). There were no differences in operative time (150.2 ± 45.1 vs. 158.6 ± 82.1, P = 0.66) and estimated blood loss (365.8 ± 298.5 vs. 356.5 ± 46.6, ml, P = 0.94) between LAVH and LSH. However, patients in LAVH had more excess blood loss (>500 mL) compared with LSH (32.7% vs. 21.7%, P = 0.42). In the later study period, the operative time was shorter and complication rates were lower. Such differences were especially significant in the LAVH group. By multiple regression analysis, operative time was independently correlated with age, body mass index, estimated blood loss and uterine weight in LAVH. The correlation between operative time and uterine weight in LSH was attenuated by estimated blood loss. Estimated blood loss was the dominant factor correlated with longer operative time in LSH. CONCLUSIONS: Both LAVH and LSH could be feasible in uteri greater than 500 g. LSH appeared to have less complication and less blood loss than LAVH. Operative time was correlated significantly with bleeding amount. Therefore, better bleeding control and surgical experience were warrants for single-port laparoscopic hysterectomy in uteri greater than 500 g.

Mediating effects of shoulder-arm exercise on the postoperative severity of symptoms and quality of life of women with breast cancer.

BACKGROUND: The postoperative severity of symptoms among women with breast cancer affects their quality of life (QoL). Although it is recommended that performing shoulder-arm exercise 30 min/day can alleviate symptoms and improve the QoL, there is little research on the mediating effects of performing shoulder-arm exercise 30 min/day on the postoperative severity of symptoms and QoL among patients with breast cancer. METHODS: A cross-sectional study was conducted 2 ~ 4 months after surgery on women diagnosed with breast cancer but with no distant metastasis and who had undergone breast cancer surgery for the first time. A structured questionnaire was employed which included a severity of symptoms scale, performing shoulder-arm exercise for 30 min/day, a QoL scale, demographic characteristics, and medical status. RESULTS: In total, 117 women with breast cancer completed the survey. The severity of symptoms and performing shoulder-arm exercise 30 min/day separately affected the QoL (B = -0.447, standard error (SE) = 0.050, p < 0.001; B = 15.666, SE = 4.542, p = 0.001, respectively). In model 3, performing shoulder-arm exercise for 30 min/day played a partial mediating role in the relationship of the severity of symptoms and QoL (R2 = 0.51, F = 5.41, p < 0.001). CONCLUSIONS: During 2 ~ 4 months after surgery, regular shoulder-arm exercise for 30 min/day could decrease the effect of the severity of symptoms on the QoL among women with breast cancer. Clinical healthcare providers may inform and educate patients as to the benefits of regular shoulder-arm exercise for 30 min/day.

GnRHa Before Single-Port Laparoscopic Hysterectomy in a Large Barrel-Shaped Uterus.

BACKGROUND AND OBJECTIVES: Laparoscopic hysterectomy for a large barrel-shaped uterus is difficult. We assessed the feasibility of single-port laparoscopic hysterectomy in a large barrel-shaped uterus after gonadotropin-releasing hormone agonist (GnRHa). METHODS: We retrospectively reviewed 39 patients with a large barrel-shaped uterus who were treated with GnRHa (leuprolide acetate) before single-port laparoscopic hysterectomy. During the same period, 134 patients without GnRHa pretreatment were included as control subjects. RESULTS: Patients with GnRHa treatment had an average increase in hemoglobin of 3.0 mg/dL and a decrease in uterine weight of 330.9 g (40.1%). Ancillary ports were required in 2 patients in the treatment group and none in the control group. There were no differences in uterine weights, operative time, and estimated blood loss in the 2 groups of patients. The estimated average operative time was shortened by 34 min after GnRHa treatment. However, bladder and ureter injuries were marginally higher (10.3% versus 2.2%) and days of hospital stay (3.7 versus 3.1) were significantly longer in the treatment group compared with controls. Complication rates were correlated with previous operative history, pelvic adhesion, and larger uterine weight but not with GnRHa treatment and operative sequence. CONCLUSIONS: GnRHa pretreatment in patients with a large barrel-shaped uterus during SPH is feasible with shortened operative time. However, the higher complication rates in these patients suggest that a weight-reduced barrel-shaped uterus that is achieved with GnRHa treatment could still be difficult and should be handled in cautious.

Robotic myomectomy for large uterine myomas.

OBJECTIVE: To evaluate surgical outcomes and feasibility of robotic myomectomy in large uterine myomas. MATERIALS AND METHODS: This is a retrospective study for robotic myomectomies performed from October 2012 to August 2017 by a single surgeon in a tertiary care referral hospital. Demographics, diagnosis, perioperative variables, operative outcomes and complications were recorded. Large uterine myoma was defined as the estimated diameter of dominant myoma equal to or larger than 10 cm by sonography. RESULTS: Seventy-four patients were included and 32 (43.2%) patients had large uterine myoma. Patients with myoma larger than 10 cm showed significantly heavier myoma weight (446.5 ± 206.2 mg vs. 288.1 ± 147.5, p < 0.001), similar blood loss (309.4 ± 190.3 mL vs. 200.9 ± 285.9 mL, p = 0.06), and longer operative time (263.4 ± 83.7 min vs. 219.1 ± 75.7 min, p = 0.02) compared with patients with myoma <10 cm. The largest myoma removed was 20 cm in diameter. Perioperative complications were rare. CONCLUSION: Robotic myomectomy is feasible for managing large uterine myomas. It is a safe procedure with acceptable longer operative time.

Palliative care for advanced dementia: Knowledge and attitudes of long-term care staff.

AIMS AND OBJECTIVES: To investigate the knowledge of and attitudes towards palliative care for advanced dementia and their associations with demographics among nursing staff, including nurses and nursing assistants, in long-term care settings. BACKGROUND: Nursing facilities are places where persons with dementia die; therefore, providing quality end-of-life care to residents with advanced dementia is crucial. To date, little attention has been paid to palliative care practice for patients with advanced dementia. DESIGN: A descriptive, cross-sectional, survey design was used. METHODS: In total, a sample of 300 nurses (n = 125) and nursing assistants (n = 175) working in long-term care settings in Taiwan participated in this study. Two instruments were administered: demographic characteristics and responses to the Questionnaire of Palliative Care for Advanced Dementia. Descriptive statistics and multiple regression were used for data analysis. RESULTS: Overall, the nurses and nursing assistants had moderate mean scores for both knowledge of and attitudes regarding palliative care for advanced dementia. Additionally, nursing staff who were nurses with greater work experience and those who had received palliative care and hospice training had greater knowledge of palliative care. In addition, nursing staff who had received dementia care training and who had worked in nursing homes had higher levels of positive attitudes towards palliative care. CONCLUSIONS: This study indicates the need to provide nurses and nursing assistants with more information about palliative care practice for people with advanced dementia. Particularly, providing education to those who are nursing assistants, who have less working experience, who have not received palliative and dementia care training, and who have not worked in nursing homes can improve overall nursing staff knowledge of and attitudes towards palliative care. RELEVANCE TO CLINICAL PRACTICE: Continuing education in principles of palliative care for advanced dementia is necessary for currently practicing nursing staff and should be developed according to their educational background and needs.

Outcomes of Patients With Surgically and Pathologically Staged IIIA-IVB Pure Endometrioid-type Endometrial Cancer: A Taiwanese Gynecology Oncology Group (TGOG-2005) Retrospective Cohort Study (A STROBE-Compliant Article).

In the management of patients with advanced-stage pure endometrioid-type endometrial cancer (E-EC), such as positive lymph nodes (stage III) or stage IV, treatment options are severely limited. This article aims to investigate the outcome of women with FIGO III-IV E-EC (based on FIGO 2009 system). The retrospective cohort study, based on the Taiwanese Gynecologic Oncology Group (TGOG-2005), enrolled patients undergoing staging surgery to have a pathologically confirmed FIGO III-IV E-EC from 22-member hospitals between 1991 and 2010. This cohort included 541 patients (stage III, n = 464; stage IV, n = 77). Five-year overall survival (OS) was 70.4%. Median progression-free survival (PFS) was 43 months (range 0-258 months) and median OS was 52 months (range 1-258 months). Multivariate analysis showed that FIGO stage, >1/2 myometrial invasion (hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.12-2.09; P = 0.007), histological grade 3 (HR 2.0, 95% CI 1.47-2.75; P < 0.001), and metastases of pelvic and para-aortic lymph nodes (PLN and PALN) (HR 2.75, 95% CI 1.13-6.72; P < 0.001) were independent risk factors for PFS. FIGO stage, >1/2 myometrial invasion (HR 1.89, 95% CI 1.34-2.64; P < 0.001), and histological grade 3 (HR 2.42, 95% CI 1.75-3.35; P < 0.001) influenced OS. Complete dissection of PLN and PALN (HR 0.27, 95% CI 0.16-0.45; P < 0.001, and HR 0.14, 95% CI 0.08-0.26; P < 0.001) and the following paclitaxel-based therapy (HR 0.61, 95% CI 0.79-0.92; P = 0.017, and HR 0.48; 95% CI 0.31-0.75; P = 0.001) provided the better PFS and OS, respectively. In management of women with FIGO III-V E-EC, combination of complete staging surgery (complete dissection of PLN and PALN is included) and the following paclitaxel-based therapy could provide the better chance to survive. Patients with tumor >1/2 myometrial invasion and histological grade 3 are risky for disease-related mortality.

Outcome of ovarian preservation during surgical treatment for endometrial cancer: A Taiwanese Gynecologic Oncology Group study.

OBJECTIVE: The goal of this study was to investigate the impact of ovarian preservation on the survival of women with early-stage endometrial cancer, particularly young women. MATERIALS AND METHODS: A study cohort of 64 patients with histologically confirmed early-stage endometrial cancer was retrospectively collected from 10 member hospitals of the Taiwanese Gynecologic Oncology Group between 1998 and 2009. Survivorship and overall survival were compared between these two groups using a log-rank test. RESULTS: All patients who underwent surgery were adult women with a mean age of 40.4 ± 9.2 years (range 24-63 years). Ovary-preserving surgery was performed in 38 (59.4%) patients who desired to preserve their ovaries, incidentally in 19 (29.7%) patients with a preoperative diagnosis other than endometrial carcinoma, and in seven patients (10.9%) with unknown reasons. The 5-year recurrence-free survival rate was 98.3% with a median follow up of 44.6 months (range 1.0-126.9 months). Eight patients required adjuvant treatment (12.5%); one patient had documented local recurrence (1.6%); and no metachronous ovarian malignancy occurred during follow up. CONCLUSION: Preservation of bilateral ovaries does not increase cancer-related mortality. A more conservative approach to surgical staging may be considered in premenopausal women with early-stage endometrial cancer without risk factors.

Primary treatment and prognostic factors of carcinosarcoma of the ovary, fallopian tube, and peritoneum: a Taiwanese Gynecologic Oncology Group Study.

OBJECTIVE: This study aimed to determine the clinical prognostic factors involved in carcinosarcoma of the ovary, fallopian tube, and peritoneum. MATERIALS AND METHODS: This retrospective study was undertaken by the Taiwanese Gynecologic Oncology Group. The retrieved clinical data included demographic characteristics, medical disease, tumor status, extent of surgery, and adjuvant chemotherapy. RESULTS: In total, 63 patients with carcinosarcoma of the ovary, fallopian tube, and peritoneum were identified. Sixty-one patients with complete data were enrolled for further data analysis. The mean follow-up period was 1.0 year, and the mean overall survival was 15.4 months. By log-rank tests, age, menopausal status, parity, hypertension, diabetes, primary tumor size, para-aortic lymph node metastasis, pretreatment CA-125, preceding diagnostic surgery, hysterectomy, lymphadenectomy, other surgeries, and paclitaxel use were not predictive of overall survival.Omentectomy, no gross residual implants after surgery, platinum treatment, and no pelvic lymph node metastasis had a trend toward better survival. Early diagnosis at stage I and cisplatin/ifosfamide regimen were significant associated with a better overall survival in log-rank and simple Cox regression tests. Bilateral ovarian tumors and metastatic tumors larger than 2 cm were significantly associated with a poorer overall survival. CONCLUSIONS: Early diagnosis at stage I, unilateral ovarian tumor, metastatic tumors less than 2 cm, and cisplatin/ifosfamide regimen were predictive of a better survival.Omentectomy and complete debulking surgery also showed a trend toward better survival. Thus, these treatment strategies should be applied in patients with carcinosarcoma of the ovary, fallopian tube, and peritoneum.

PRSS23 is essential for the Snail-dependent endothelial-to-mesenchymal transition during valvulogenesis in zebrafish.

AIMS: Cardiac valve disease is a common cause of congenital heart failure. Cardiac valve development requires a complex regulation of assorted protease activities. Nevertheless, the regulation of these proteases during atrioventricular (AV) valve formation is poorly understood. Previously, PRSS23, a novel vascular protease, is shown to be highly expressed at the AV canal during murine heart development; however, its function remains unknown. In this study, we sought to characterize the functional role of PRSS23 during cardiac valve formation. METHODS AND RESULTS: We used a transgenic zebrafish line with fluorescently labelled vasculature as a tool to study the function of PRSS23. We first cloned the zebrafish prss23 and confirmed its sequence conservation with other vertebrate orthologues. Expression of prss23 was detected in the ventricle, atrium, and AV canal during zebrafish embryonic development. We found that morpholino knockdown of Prss23 inhibited the endothelial-to-mesenchymal transition (EndoMT) at the AV canal. Moreover, in human aortic endothelial cell-based assays, PRSS23 knockdown by short-hairpin RNA not only repressed the transforming growth factor-ß-induced EndoMT, but also reduced Snail transcription, suggesting that Snail signalling is downstream of PRSS23 during EndoMT. We further demonstrated that human PRSS23 and SNAIL could rescue the prss23 morpholino-induced AV canal defect in zebrafish embryos, indicating that the function of PRSS23 in valvulogenesis is evolutionarily conserved. CONCLUSION: We demonstrated for the first time that the initiation of EndoMT in valvulogenesis depends on PRSS23-Snail signalling and that the functional role of PRSS23 during AV valve formation is evolutionarily conserved.

Inhibition of gap junctional Intercellular communication in WB-F344 rat liver epithelial cells by triphenyltin chloride through MAPK and PI3-kinase pathways.

BACKGROUND: Organotin compounds (OTCs) have been widely used as stabilizers in the production of plastic, agricultural pesticides, antifoulant plaints and wood preservation. The toxicity of triphenyltin (TPT) compounds was known for their embryotoxic, neurotoxic, genotoxic and immunotoxic effects in mammals. The carcinogenicity of TPT was not well understood and few studies had discussed the effects of OTCs on gap junctional intercellular communication (GJIC) of cells. METHOD: In the present study, the effects of triphenyltin chloride (TPTC) on GJIC in WB-F344 rat liver epithelial cells were evaluated, using the scrape-loading dye transfer technique. RESULTS: TPTC inhibited GJIC after a 30-min exposure in a concentration- and time-dependent manner. Pre-incubation of cells with the protein kinase C (PKC) inhibitor did not modify the response, but the specific MEK 1 inhibitor PD98059 and PI3K inhibitor LY294002 decreased substantially the inhibition of GJIC by TPTC. After WB-F344 cells were exposed to TPTC, phosphorylation of Cx43 increased as seen in Western blot analysis. CONCLUSIONS: These results show that TPTC inhibits GJIC in WB-F344 rat liver epithelial cells by altering the Cx43 protein expression through both MAPK and PI3-kinase pathways.