MiR-4521 perturbs FOXM1-mediated DNA damage response in breast cancer

Introduction: Forkhead (FOX) transcription factors are involved in cell cycle control, cellular differentiation, maintenance of tissues, and aging. Mutation or aberrant expression of FOX proteins is associated with developmental disorders and cancers. FOXM1, an oncogenic transcription factor, is a promoter of cell proliferation and accelerated development of breast adenocarcinomas, squamous carcinoma of the head, neck, and cervix, and nasopharyngeal carcinoma. High FOXM1 expression is correlated with chemoresistance in patients treated with doxorubicin and Epirubicin by enhancing the DNA repair in breast cancer cells.Method: miRNA-seq identified downregulation of miR-4521 in breast cancer cell lines. Stable miR-4521 overexpressing breast cancer cell lines (MCF-7, MDA-MB-468) were developed to identify miR-4521 target gene and function in breast cancer.Results: Here, we showed that FOXM1 is a direct target of miR-4521 in breast cancer. Overexpression of miR-4521 significantly downregulated FOXM1 expression in breast cancer cells. FOXM1 regulates cell cycle progression and DNA damage response in breast cancer. We showed that miR-4521 expression leads to increased ROS levels and DNA damage in breast cancer cells. FOXM1 plays a critical role in ROS scavenging and promotes stemness which contributes to drug resistance in breast cancer. We observed that breast cancer cells stably expressing miR-4521 lead to cell cycle arrest, impaired FOXM1 mediated DNA damage response leading to increased cell death in breast cancer cells. Additionally, miR-4521-mediated FOXM1 downregulation perturbs cell proliferation, invasion, cell cycle progression, and epithelial-to-mesenchymal progression (EMT) in breast cancer.Discussion: High FOXM1 expression has been associated with radio and chemoresistance contributing to poor patient survival in multiple cancers, including breast cancer. Our study showed that FOXM1 mediated DNA damage response could be targeted using miR-4521 mimics as a novel therapeutic for breast cancer

Analysis of mitochondrial DNA variations in Indian patients with congenital cataract

PURPOSE: Identification of mitochondrial DNA (mtDNA) variations in the inherited cataract patients from south India. METHODS: Three families with inherited cataract of maternal origin were evaluated. Clinical and ophthalmologic examinations were performed on available affected as well as unaffected family members. Samples of mtDNA were amplified using 24 pairs of overlapping primers to analyze the entire mitochondrial genome to screen for variations and analyzed for both coding and non-coding regions. Bioinformatic analysis was performed to evaluate the effect of nucleotide variations. RESULTS: DNA sequence analysis of inherited cataract families showed 72 nucleotide variations, of which 15 were observed in the major non-coding D-loop region, 3 in the tRNA genes, 5 in the rRNA genes, and 49 in the protein coding region. Among these variations 56 were reported previously and 16 were novel of which, 12 synonymous substitutions, 2 non-synonymous substitutions along with a frameshift mutation, and one was in the non-coding region. Nicotinamide adenine dinucleotide dehydrogenase (NADH) subunit (ND) gene of mtDNA was highly altered, in general, and found to contain 4 variations specific for cataract patients of the first family, six for the second, and one for the third family. CONCLUSIONS: Seventy-two variations were observed in three inherited cataract families. Four variations were specific for cataract patients of the first family, six for the second, and one for the third family. This is perhaps the first report on the presence of mitochondrial mutations in inherited cataracts

Antimicrobial efficacy of Kerr pulp canal sealer (EWT) in combination with 10% amoxicillin on Enterococcus faecalis: A confocal laser scanning microscopic study [version 2; peer review: 1 approved, 2 approved with reservations]

Background: Sealers with antimicrobial properties play an important role in endodontic therapy success especially against Enterococcus faecalis infection found in failed root canal therapy. Addition of antibiotic agents to endodontic sealers may show significant increase in their antibacterial properties both against anaerobic and aerobic microbes. The purpose of the present study was to evaluate antimicrobial efficacy of Kerr pulp canal sealer (EWT) in combination with 10% amoxicillin against E. faecalis and post-root canal treatment viability of Enterococcus faecalis on the first and seventh day. Methods: A total of 60 extracted human mandibular premolar teeth were decoronated after initial decontamination with 1% NaOCl. Root length standardized to 12 mm. Canal instrumentation was done using ProTaper Universal file system till size F2 using 5.25% NaOCl. It was then infected with a pure strain of E. faecalis for a period of four days. Obturation was done using plain sealer, (n=30) and sealer-antibiotic combination, (n=30). Half of the teeth were sectioned at 24 hours (S, SA) and other half were sectioned seven days after obturation (S7, SA7). All samples were stained with SYTO9 and propidium iodide for imaging under Confocal Laser Scanning microscope. Statistical analysis was performed with the statistical software SPSS v. 17.0 (SPSS for Windows; SPSS Inc, Chicago, IL). Data was analysed using One Way ANOVA and post hoc Tukey test to determine statistical significance with p value < 0.01 considered significant. Results: Statistically significant differences were observed in green to red ratio between group S (9.561976) and S7 (0.435418) (p < 0.01). There was no difference found between SA (mean of green to red ratio, (0.70431) and SA7 (mean of green to red ratio, 0.85184). Conclusions: Antibiotics added to the sealer effectively eradicated of E. faecalis 24 hours post-obturation. However, after seven days, plain sealer was as effective as sealer-antibiotic combination

Antimicrobial efficacy of Kerr pulp canal sealer (EWT) in combination with 10% amoxicillin on Enterococcus faecalis: A confocal laser scanning microscopic study [version 1; peer review: 1 approved, 2 approved with reservations]

Background: Sealers with antimicrobial properties play an important role in endodontic therapy success especially against Enterococcus faecalis infection found in failed root canal therapy. Addition of antibiotic agents to endodontic sealers may show significant increase in their antibacterial properties both against anaerobic and aerobic microbes. The purpose of the present study was to evaluate antimicrobial efficacy of Kerr pulp canal sealer (EWT) in combination with 10% amoxicillin against E. faecalis and post-root canal treatment viability of Enterococcus faecalis on the first and seventh day. Methods: A total of 60 extracted human mandibular premolar teeth were decoronated after initial decontamination with 1% NaOCl. Root length standardized to 12 mm. Canal instrumentation was done using ProTaper Universal file system till size F2 using 5.25% NaOCl. It was then infected with a pure strain of E. faecalis for a period of four days. Obturation was done using plain sealer, (n=30) and sealer-antibiotic combination, (n=30). Half of the teeth were sectioned at 24 hours (S, SA) and other half were sectioned seven days after obturation (S7, SA7). All samples were stained with SYTO9 and propidium iodide for imaging under Confocal Laser Scanning microscope. Statistical analysis was performed with the statistical software SPSS v. 17.0 (SPSS for Windows; SPSS Inc, Chicago, IL). Data was analysed using One Way ANOVA and post hoc Tukey test to determine statistical significance with p value < 0.01 considered significant. Results: Statistically significant differences were observed in green to red ratio between group S (9.561976) and S7 (0.435418) (p < 0.01). There was no difference found between SA (mean of green to red ratio, (0.70431) and SA7 (mean of green to red ratio, 0.85184). Conclusions: Antibiotics added to the sealer effectively eradicated of E. faecalis 24 hours post-obturation. However, after seven days, plain sealer was as effective as sealer-antibiotic combination

In vitro evaluation of cytotoxicity and corrosion behavior of commercially pure titanium and Ti-6Al-4V alloy for dental implants

Purpose: The aim of this study was to investigate the cytotoxicity in human gingival fibroblast by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and corrosion behavior by potentiodynamic polarization technique of commercially pure titanium (Ti 12) and its alloy Ti-6Al-4V (Ti 31). Materials and Methods: In the present in vitro study, cytotoxicity of Ti 12 and Ti 31 in human gingival fibroblast by MTT assay and the corrosion behavior by potentiodynamic polarization technique in aqueous solutions of 0.1 N NaCl, 0.1 N KCl, and artificial saliva with and without NaF were studied. Results: The independent t-test within materials and paired t-test with time interval showed higher cell viability for Ti 12 compared to Ti 31. Over a period, cell viability found to stabilize in both Ti 12 and Ti 31. The effects of ions of Ti and alloying elements aluminum and vanadium on the cell viability were found with incubation period of cells on samples to 72 h. The electrochemical behavior of Ti 12 and Ti 31 in different experimental solutions showed a general tendency for the immersion potential to shift steadily toward nobler values indicated formation of TiO2and additional metal oxides. The multiphase alloy Ti-6Al-4V showed more surface pitting. Conclusion: The commercially pure Ti showed better cell viability compared to Ti 31. Less cell viability in Ti 31 is because of the presence of aluminum and vanadium. A significant decrease in cytotoxicity due to the formation of TiO2over a period of time was observed both in Ti 12 and Ti 31. The electrochemical behavior of Ti 12 and Ti 31 in different experimental solutions showed a general tendency for the immersion potential to shift steadily toward nobler values indicated formation of TiO2 and additional metal oxides. Ti 31 alloy showed surface pitting because of its multiphase structure

Molecular implications of HOX genes targeting multiple signaling pathways in cancer.

Homeobox (HOX) genes encode highly conserved homeotic transcription factors that play a crucial role in organogenesis and tissue homeostasis. Their deregulation impacts the function of several regulatory molecules contributing to tumor initiation and progression. A functional bridge exists between altered gene expression of individual HOX genes and tumorigenesis. This review focuses on how deregulation in the HOX-associated signaling pathways contributes to the metastatic progression in cancer. We discuss their functional significance, clinical implications and ascertain their role as a diagnostic and prognostic biomarker in the various cancer types. Besides, the mechanism of understanding the theoretical underpinning that affects HOX-mediated therapy resistance in cancers has been outlined. The knowledge gained shall pave the way for newer insights into the treatment of cancer

Human Papillomavirus (HPV) Infection in Early Pregnancy: Prevalence and Implications

Introduction. Young women (20-35 years) are at high risk of HPV infection, although the majority of the infections are asymptomatic and are cleared spontaneously by the host immune system. These are also the group of women who are sexually active and are in the population of pregnant women. During pregnancy, the changes in the hormonal milieu and immune response may favor persistence of HPV infection and may aid in transgenerational transmission thereby furthering the cancer risk. In the present study, we determined the prevalence of vaginal HPV infection in early pregnancy and attempted to relate with pregnancy outcome. Material and Methods. Vaginal cytology samples were collected from the condoms used to cover the vaginal sonography probe during a routine first trimester visit to the hospital. All women were followed up throughout pregnancy and childbirth. Maternal and neonatal outcomes were recorded. Results. We found a prevalence of HPV infection around 39.4% in our population. Interestingly all HPV positive women were infected with one or more high risk HPV viruses with an overlap of intermediate and low risk in 43% and 7.3%, respectively. Women with preterm prelabor rupture of membranes (PPROM) showed a statistically higher incidence in HPV positive (7.3%) group as compared to the HPV negative (3.2%) group. Conclusion. The prevalence of genital HPV infection is high during pregnancy (around 40%) and was associated with higher incidence of PPROM

Understanding triethylammonium hydrogen sulfate ([TEA][HSO<inf>4</inf>]) pretreatment induced changes in Pennisetum polystachion cell wall matrix and its implications on biofuel yield

11 páginas, 3 tablas, 9 figurasBiofuel potential of a widely grown perennial grass, Pennisetum polystachion, was analyzed using triethylammonium hydrogen sulfate ([TEA][HSO4]) pretreatment. The optimum pretreatment condition was selected based on the delignification efficiency. 80% [TEA][HSO4] at 140 °C for 45 min at 10% sample load, yielding high delignification rate (65.8%) was selected as the optimum pretreatment condition. Recycling of [TEA][HSO4] showed up to 90% IL recovery and significant delignification rates. Glucan yield in the biomass increased to 67.8%, whereas digestibility of biomass enhanced from 16.7% to 84.1%. Extensive deferuloylation (88%) and decoumarylation (86.4%) were observed in the sample following pretreatment. Diferulic acids were not detected in pretreated samples indicating their complete removal. HMF (0.1 mg/mL) and furfural (0.001 mg/mL) produced during pretreatment were very low compared to conventional methods. FTIR and XRD confirmed pronounced delignification and hemicellulose dissolution, and FESEM showed a marked difference in the surface morphology, including defibrillation and enhanced porosity. An ethanol yield of 275 mg/g biomass (84.7% of theoretical maxima) was achieved using Saccharomyces cerevisiae MTCC 36 after 15 h of fermentation. The results obtained from the current study can shed light on utilizing P. polystachion as a potential biofuel feedstock using a low-cost ionic liquid [TEA][HSO4].The present study did not receive any specific grants from public, commercial or not-for-profit agencies.Peer reviewe