The profile of Oral Health Branch of Rafsanjan Cohort Study (OHBRCS) in Rafsanjan City, southeast of Iran.

Oral health status can be affected by some factors including drug abuse, systemic conditions and environmental pollutants. The present study was designed to investigate the most important and prevalent dental and oral conditions in adult population of Rafsanjan with the age of 35-70 years. Dental and oral health cohort center as part of the Rafsanjan Cohort Study (RCS) included in the prospective epidemiological research studies in IrAN was established in 2015. Of 9991 subjects enrolled in the RCS, 8682 people participated in the Oral Health Branch of Rafsanjan Cohort Study (OHBRCS). The OHBRCS included 4021 men and 4661 women with the mean age of 49.94 ± 9.51. The most prevalent of oral lesion in total population was candidiasis and the least was aphthous lesion. The prevalence of candidiasis, white and red lesions, periodontal pocket, dental calculus, CAL and the mean of DMFT were higher in the male group than that of female group (p < 0.05). Candidiasis, herpes, oral cancer, white and red lesions were more prevalent in the older age groups (p < 0.05). The mean of DMFT index in total population was 21.30 and was higher among opium users, men and older age (p < 0.05). Also, the opium users had a higher rate of CAL, periodontal pocket, red and white lesions, and candidiasis but a lower rate of BOP (p < 0.05). Younger people had more decayed and filling teeth compared to other age groups, whereas older people had more missing teeth and a higher DMFT index (p < 0.001).

Dyslipidemia, diabetes and periodontal disease, a cross-sectional study in Rafsanjan, a region in southeast Iran.

THE OBJECTIVES: The association between dyslipidemia, diabetes and alterations in periodontal health are inconsistent. The aim of this study was to determine the association between dyslipidemia, diabetes and periodontal disease in the Oral Health Branch of Rafsanjan Cohort Study (OHBRCS). METHODS: Rafsanjan Cohort Study (RCS) was launched in 2015 in Rafsanjan City a region in the southeast of Iran. A total of 8682 participants aged 35-70 years of both gender were recruited into the OHBRCS as a part of RCS. Bleeding on probing (BOP), probing pocket depth (PPD) and Clinical attachment loss (CAL) were used to assess periodontal health status. When CAL progression was ≥ 1 mm and PPD was > 3 mm, it was defined as periodontitis. RESULTS: The final sample consisted of 6751 individuals with mean age of 47.67 ± 8.79 years. Among this population, 73.32% (n = 4949), 13.75% (n = 928), 59.67% (n = 4028) and 11.76% (n = 794) had BOP, PPD > 3 mm, CAL ≥ 1 mm and periodontitis respectively. The odds of CAL ≥ 1 mm increased 14% in subjects with high LDL cholesterol (OR: 1.14; 95% CI: 1.01-1.30), 17% in subjects with diabetes (OR: 1.17; 95% CI: 1.01-1.36) and 23% in subjects with both dyslipidemia and diabetes (OR: 1.23; 95% CI: 1.05-1.44). Also, the odds of PPD > 3 mm in the group with high total cholesterol (TC) was 16% higher compared to those with normal TC (OR: 1.16; 95% CI: 1.01-1.34). CONCLUSIONS: There was an increased odds in periodontal disease in association with high TC, high LDL cholesterol, diabetes and having both dyslipidemia and diabetes. This suggests that high TC, high LDL cholesterol, diabetes and having both dyslipidemia and diabetes might be potential indicators for the presence of periodontal disease.

Fracture Resistance of a Bulk-Fill and a Conventional Composite and the Combination of Both for Coronal Restoration of Severely Damaged Primary Anterior Teeth.

OBJECTIVES: This study aimed to compare the fracture resistance of a bulk-fill and a conventional composite and a combination of both for coronal restoration of severely damaged primary anterior teeth. MATERIALS AND METHODS: In this in vitro experimental study, 45 primary anterior teeth were randomly divided into three groups. After root canal preparation, the canals were filled with Metapex paste such that after the application of 1 mm of light-cure liner, 3 mm of the coronal third of the canal remained empty for composite post fabrication. Filtek Z250 conventional composite was used in group 1, Sonic-Fill bulk-fill composite was used in group 2 and Sonic-Fill with one layer of Filtek Z250 as the veneering were used in group 3. Adper Single Bond 2 was used in all groups. The teeth were thermocycled, and fracture resistance was measured by a universal testing machine. The mode of fracture was categorized as repairable or irreparable. Data were analyzed using one-way ANOVA. RESULTS: The mean fracture resistance was 307.00±74.72, 323.31±84.28 and 333.30±63.96 N in groups 1 to 3, respectively (P=0.55). The mean fracture strength was 14.53±2.98, 15.08±2.82 and 15.26±3.02 MPa in groups 1 to 3, respectively (P=0.77). The frequency of repairable mode of failure was 80% for the conventional, 73.6% for the bulk-fill and 80% for the bulk-fill plus conventional group, with no significant difference (P>0.05). CONCLUSION: Bulk-fill composites can be used for coronal reconstruction of severely damaged primary anterior teeth similar to conventional composites to decrease the treatment time in pediatric patients.

Mechanisms and Antitumor Activity of a Binary EGFR/DNA-Targeting Strategy Overcomes Resistance of Glioblastoma Stem Cells to Temozolomide.

PURPOSE: Glioblastoma (GBM) is a fatal primary malignant brain tumor. GBM stem cells (GSC) contribute to resistance to the DNA-damaging chemotherapy, temozolomide. The epidermal growth factor receptor (EGFR) displays genomic alterations enabling DNA repair mechanisms in half of GBMs. We aimed to investigate EGFR/DNA combi-targeting in GBM. EXPERIMENTAL DESIGN: ZR2002 is a "combi-molecule" designed to inflict DNA damage through its chlorethyl moiety and induce irreversible EGFR tyrosine kinase inhibition. We assessed its in vitro efficacy in temozolomide-resistant patient-derived GSCs, mesenchymal temozolomide-sensitive and resistant in vivo-derived GSC sublines, and U87/EGFR isogenic cell lines stably expressing EGFR/wild-type or variant III (EGFRvIII). We evaluated its antitumor activity in mice harboring orthotopic EGFRvIII or mesenchymal TMZ-resistant GSC tumors. RESULTS: ZR2002 induced submicromolar antiproliferative effects and inhibited neurosphere formation of all GSCs with marginal effects on normal human astrocytes. ZR2002 inhibited EGF-induced autophosphorylation of EGFR, downstream Erk1/2 phosphorylation, increased DNA strand breaks, and induced activation of wild-type p53; the latter was required for its cytotoxicity through p53-dependent mechanism. ZR2002 induced similar effects on U87/EGFR cell lines and its oral administration significantly increased survival in an orthotopic EGFRvIII mouse model. ZR2002 improved survival of mice harboring intracranial mesenchymal temozolomide-resistant GSC line, decreased EGFR, Erk1/2, and AKT phosphorylation and was detected in tumor brain tissue by MALDI imaging mass spectrometry. CONCLUSIONS: These findings provide the molecular basis of binary EGFR/DNA targeting and uncover the oral bioavailability, blood-brain barrier permeability, and antitumor activity of ZR2002 supporting potential evaluation of this first-in-class drug in recurrent GBM.

Sensitivity to PRIMA-1MET is associated with decreased MGMT in human glioblastoma cells and glioblastoma stem cells irrespective of p53 status.

Alterations of the TP53 tumor suppressor gene occur in ~30% of primary glioblastoma (GBM) with a high frequency of missense mutations associated with the acquisition of oncogenic "gain-of-function" (GOF) mutant (mut)p53 activities. PRIMA-1MET/APR-246, emerged as a promising compound to rescue wild-type (wt)p53 function in different cancer types. Previous studies suggested the role of wtp53 in the negative regulation of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT), a major determinant in resistance to therapy in GBM treatment. The potential role of MGMT in expression of p53 and the efficacy of PRIMA-1MET with respect to TP53 status and expression of MGMT in GBM remain unknown. We investigated response to PRIMA-1MET of wtp53/MGMT-negative (U87MG, A172), mutp53/MGMT-positive U138, LN-18, T98/Empty vector (T98/EV) and its isogenic MGMT/shRNA gene knockdown counterpart (T98/shRNA). We show that MGMT silencing decreased expression of mutp53/GOF in T98/shRNA. PRIMA-1MET further cleared T98/shRNA cells of mutp53, decreased proliferation and clonogenic potential, abrogated the G2 checkpoint control, increased susceptibility to apoptotic cell death, expression of GADD45A and sustained expression of phosphorylated Erk1/2. PRIMA-1MET increased expression of p21 protein in U87MG and A172 and promoted senescence in U87MG cell line. Importantly, PRIMA-1MET decreased relative cell numbers, disrupted the structure of neurospheres of patient-derived GBM stem cells (GSCs) and enabled activation of wtp53 with decreased expression of MGMT in MGMT-positive GSCs or decreased expression of mutp53. Our findings highlight the cell-context dependent effects of PRIMA-1MET irrespective of p53 status and suggest the role of MGMT as a potential molecular target of PRIMA-1MET in MGMT-positive GSCs.

Differential response to ablative ionizing radiation in genetically distinct non-small cell lung cancer cells.

Stereotactic ablative radiotherapy (SABR) has emerged as a highly promising treatment for medically inoperable early-stage non-small cell lung cancer patients. Treatment outcomes after SABR have been excellent compared to conventional fractionated radiotherapy (CFRT). However, the biological determinants of the response to ablative doses of radiation remain poorly characterized. Furthermore, there's little data on the cellular and molecular response of genetically distinct NSCLC subtypes to radiation. We assessed the response of 3 genetically distinct lung adenocarcinoma cell lines to ablative and fractionated ionizing radiation (AIR and FIR). We studied clonogenic survival, cell proliferation, migration, invasion, apoptosis and senescence. We also investigated the effect of AIR and FIR on the expression of pro-invasive proteins, epithelial-to-mesenchymal transition (EMT), extracellular signal-regulated kinases (ERK1/2) and the transmembrane receptor cMET. Our findings reveal that AIR significantly reduced cell proliferation and clonogenic survival compared to FIR in A549 cells only. This differential response was not observed in HCC827 or H1975 cells. AIR significantly enhanced the invasiveness of A549 cells, but not HCC827 or H1975 cells compared to FIR. Molecular analysis of pathways involved in cell proliferation and invasion revealed that AIR significantly reduced phosphorylation of ERK1/2 and upregulated cMET expression in A549 cells. Our results show a differential proliferative and invasive response to AIR that is dependent on genetic subtype and independent of intrinsic radioresistance. Further examination of these findings in a larger panel of NSCLC cell lines and in pre-clinical models is warranted for identification of biomarkers of tumor response to AIR.