Anticancer Efficacy of a Difluorodiarylidenyl Piperidone (HO-3867) in Human Ovarian Cancer Cells and Tumor Xenografts

The purpose of this study was to evaluate the anticancer potency and mechanism of a novel difluorodiarylidenyl piperidone (H-4073) and its N-hydroxypyrroline modification (HO-3867) in human ovarian cancer. Studies were done using established human ovarian cancer cell lines (A2870, A2780cDDP, OV-4, SKOV3, PA-1, and OVCAR3) as well as in a murine xenograft tumor (A2780) model. Both compounds were comparably and significantly cytotoxic to A2780 cells. However, HO-3867 showed a preferential toxicity toward ovarian cancer cells while sparing healthy cells. HO-3867 induced G2-M cell cycle arrest in A2780 cells by modulating cell cycle regulatory molecules p53, p21, p27, cyclin-dependent kinase 2, and cyclin, and promoted apoptosis by caspase-8 and caspase-3 activation. It also caused an increase in the expression of functional Fas/CD95 and decreases in signal transducers and activators of transcription 3 (STAT3; Tyr705) and JAK1 phosphorylation. There was a significant reduction in STAT3 downstream target protein levels including Bcl-xL, Bcl-2, survivin, and vascular endothelial growth factor, suggesting that HO-3867 exposure disrupted the JAK/STAT3 signaling pathway. In addition, HO-3867 significantly inhibited the growth of the ovarian xenografted tumors in a dosage-dependent manner without any apparent toxicity. Western blot analysis of the xenograft tumor tissues showed that HO-3867 inhibited pSTAT3 (Tyr705 and Ser727) and JAK1 and increased apoptotic markers cleaved caspase-3 and poly ADP ribose polymerase. HO-3867 exhibited significant cytotoxicity toward ovarian cancer cells by inhibition of the JAK/STAT3 signaling pathway. The study suggested that HO-3867 may be useful as a safe and effective anticancer agent for ovarian cancer therapy

Impact of advances in diagnosis and treatment on the leading causes of death and increasing survival in patients with colorectal cancer, 1975-2009

The death rate of colorectal cancer (CRC) continued to decline in the United States during 1975 to 2009. As the diagnosis and treatment of CRC advance, more CRC patients are living longer and are more likely to die from causes other than CRC. Current knowledge on the overall impact of past achievements on outcomes of the disease is very limited, which creates a need for better understanding of the temporal trends of the survivorship and leading causes of death. Our work focused on three major aspects: First, we monitored the changing patterns of the leading causes of death in patients with CRC during 1975 to 2009; Second, we determined whether choice of chemotherapy regimens, severity of pre-existing comorbidities and chemotherapy-related toxicities made a difference in risk of death among elderly patients; Third, we estimated effect of advances in screening on tumor migration towards earlier stage and smaller size and to assess the relative contribution of advances in diagnosis and treatment on survival improvement in elderly patients

A comparative study of oral health attitudes and behavior using the Hiroshima University - Dental Behavioral Inventory (HU-DBI) between dental and civil engineering students in Colombia

The aim of this study was to use the Hiroshima University - Dental Behavioral Inventory (HU-DBI) to compare oral health attitudes and behavior of dental and civil engineering students in Colombia. The HU-DBI's survey consisting of twenty dichotomous responses (agree-disagree) regarding tooth brushing, was completed at University Antonio Narino for the dental students and the University of Cauca for the civil engineering students. The Spanish version of the HU-DBI questionnaire was taken by 182 of 247 dental students and 411 of 762 engineering students. The data was-statistically analyzed by the chi-square test and backward logistic regression. Compared to the engineering students, the dental students were more likely to agree with questions such as “I am bothered by the color of my gums”(OR = 2.2, 95% CI: 1.3-3.7),“I think I can clean my teeth well without using toothpaste” (OR = 3.0, 95% CI: 1.5-5.9), “I have used a dye to see how clean my teeth are” (OR = 2.9, 95% CI: 1.9-4.3), and “I have had my dentist tell me that I brush very well” (OR = 2.0, 95% CI: 1.3-3.1). The dental education curriculum in a dental school compared to a civil engineering school in Colombia indicated that a three-phase curriculum in didactics and clinics increased oral health attitudes and behavior from entry to graduation

Dry Eye-Related Visual Blurring and Irritative Symptoms and Their Association with Depression and Anxiety in Eye Clinic Patients

<p><i>Purpose</i>: Dry eye is a common condition known to have many systemic co-morbidities. We aim to report the frequency of depression and anxiety suspects in eye clinic patients and explore the association between dry eye signs and symptoms with depression and anxiety.</p> <p><i>Materials and methods</i>: Adult outpatients were recruited from dry a public tertiary ophthalmology specialist center. Participants underwent socio-demographic and dry eye symptoms questionnaires, fluorescein dye tear break-up time (TBUT), fluorescein dye corneal staining and Schirmer’s test. Rasch analysis was used to internally validate the Hospital Anxiety and Depression Scale (HADS) and the Center for Epidemiologic Studies Depression Scale (CES-D) and determine its psychometric properties.</p> <p><i>Results</i>: A total of 96 participants (mean age 54.5 ± 10.8; 64.1% women) were recruited. The mean score for the CES-D was 12.1 ± 9.8 with 28 participants (31.5%) having a score of above 16 (published threshold). The mean score for depression-associated questions in the HADS was 3.6 ± 3.6 with 13 participants (14.1%) having a score ≥8. The mean score for the anxiety-associated questions in the HADS was 5.3 ± 3.6 with 24 participants (26.1%) having score ≥8. There was a weak inverse correlation between Schirmer’s test and CES-D scores. Elevated depression scores from the CES-D were significantly associated with visual blurring but not irritation, in dry eye patients with low TBUT.</p> <p><i>Conclusions</i>: In conclusion, specific types of dry eye symptoms, particularly those with increased frequency of visual blurring were associated with symptoms of depression. The optical aberrations induced by dry eye, associated with tear instability, may predispose to depressive tendency.</p

Blue light attenuates TGF-β2-induced epithelial-mesenchymal transition in human lens epithelial cells via autophagy impairment

Abstract Background Pathogenesis of posterior capsular opacification (PCO) was related to pathological epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs). It has been reported that blue light could have an effect on EMT. This study aims to elucidate the role and potential mechanism of autophagy in EMT after blue light exposure in LECs. Methods HLE-B3 cells were treated with TGF-β2 with different concentration and time to induce EMT as a model of PCO in vitro. Cells were exposed to blue light with or without TGF-β2. The expression levels of EMT-associated markers were analyzed by qRT-PCR, western blotting and cell migration ability was determined by transwell migration assay and wound healing assay. The expressions of autophagy-related proteins were analyzed by western blotting, immunofluorescence and transmission electron microscopy. Rapamycin and chloroquine were utilized in cells for autophagy activation and inhibition. Results TGF-β2 induced autophagy activation during EMT progression in HLE-B3 cells in a dose- and time-dependent manner. Blue light exposure inhibited TGF-β2-induced EMT characterized by inhibited expression of EMT related markers and reduced migration capacity. Meanwhile, blue light exposure impaired autophagy activated by TGF-β2. Furthermore, Autophagy activation with rapamycin rescued EMT attenuated by blue light. Autophagy inhibition with chloroquine reduced TGF-β2-induced EMT in HLE-B3 cells. Conclusion Blue light exposure had inhibited effects on TGF-β2-induced EMT in LECs through autophagy impairment, which provides a new insight on prevention and treatment of PCO

Effect of dental education on peruvian dental students' oral health-related attitudes and behavior

This study evaluated the effect of dental education on oral health-related attitudes and behavior of students in a five-year dental program in Peru. A survey using the Hiroshima University-Dental Behavioral Inventory (HU-DBI), which consists of twenty dichotomous responses (agree-disagree) regarding oral health behavior and attitudes, was completed by Year 1 and Year 5 dental students at the Universidad Inca Garcilaso de la Vega in Lima, Peru. A total of 153 Year 1 students and 120 Year 5 students responded to the Spanish version of the HU-DBI questionnaire. The data were analyzed using chi-square tests and logistic regression analyses. Compared to the Year 1 students, the Year 5 dental students were more likely to agree with questions such as “I think I can clean my teeth well without using toothpaste” (OR=0.24, 95% CI: 0.10-0.58); “I have used a dye to see how clean my teeth are” (OR=0.19, 95% CI: 0.10-0.36); and “I have had my dentist tell me that I brush very well” (OR=0.34, 95% CI: 0.17-0.69). Overall, the data showed that the curriculum in this dental school in Peru resulted in more positive oral health-related attitudes and behavior among Year 5 dental students compared to those of Year 1 dental students

Effect of dental education on peruvian dental students' oral health-related attitudes and behavior

This study evaluated the effect of dental education on oral health-related attitudes and behavior of students in a five-year dental program in Peru. A survey using the Hiroshima University-Dental Behavioral Inventory (HU-DBI), which consists of twenty dichotomous responses (agree-disagree) regarding oral health behavior and attitudes, was completed by Year 1 and Year 5 dental students at the Universidad Inca Garcilaso de la Vega in Lima, Peru. A total of 153 Year 1 students and 120 Year 5 students responded to the Spanish version of the HU-DBI questionnaire. The data were analyzed using chi-square tests and logistic regression analyses. Compared to the Year 1 students, the Year 5 dental students were more likely to agree with questions such as “I think I can clean my teeth well without using toothpaste” (OR=0.24, 95% CI: 0.10-0.58); “I have used a dye to see how clean my teeth are” (OR=0.19, 95% CI: 0.10-0.36); and “I have had my dentist tell me that I brush very well” (OR=0.34, 95% CI: 0.17-0.69). Overall, the data showed that the curriculum in this dental school in Peru resulted in more positive oral health-related attitudes and behavior among Year 5 dental students compared to those of Year 1 dental students.Revisión por pare

A Review of Intraocular Pressure (IOP) and Axial Myopia

The pathogenesis of myopia is driven by genetic and environmental risk factors. Accommodation not only alters the curvature and shape of the lens but also involves contraction of the ciliary and extraocular muscles, which influences intraocular pressure (IOP). Scleral matrix remodeling has been shown to contribute to the biomechanical susceptibility of the sclera to accommodation-induced IOP fluctuations, resulting in reduced scleral thickness, axial length (AL) elongation, and axial myopia. The rise in IOP can increase the burden of scleral stretching and cause axial lengthening. Although the accommodation and IOP hypotheses were proposed long ago, they have not been validated. This review provides a brief and updated overview on studies investigating the potential role of accommodation and IOP in myopia progression