An Investigation of the Risk Factors of Osteoporosis and the Correlation between Opium Consumption and Osteoporosis in Adults

Background: Osteoporosis and osteopenia are the most common metabolic bone diseases making the patients vulnerable to bone fragility and fracture. In this study, the association of opium consumption and osteoporosis adjusted for other risk factors was studied.Methods: In this cross-sectional study, 619 cases including 73 men and 546 women referred to densitometry center in Kerman, Iran, were studied. Demographic information, history of opium consumption, medications, and other risk factors were collected using a structured questionnaire.Findings: In a univariate analysis, opium consumption, aging, and having a body mass index (BMI) lower than 24 accompanied an increased chance of osteoporosis, while taking physical exercises on a daily basis reduces the chance of osteoporosis. Through multivariable analysis, the two variables of age group and BMI group turned out to be of significance; that is, the chance of osteoporosis or osteopenia in the age group of higher than 60 years and 45-60 years being placed in one of the levels of osteoporosis or osteopenia was 4.9 and 3.1 times higher than the age groups lower than 45 years, respectively, after being adjusted to the other variables.Conclusion: Considering the results of this study, though the risk of bone density reduction in the individuals consuming opium was higher, due to the disparity between opium consumption in the two sexes, the difference was not significant between the two groups, and it is proposed that studies on larger samples and in the both sexes be conducted to determine the impacts of opium on the bone density

Targeted Long-Read Bisulfite Sequencing Identifies Differences in the TERT Promoter Methylation Profiles between TERT Wild-Type and TERT Mutant Cancer Cells

Background: TERT promoter methylation, located several hundred base pairs upstream of the transcriptional start site, is cancer specific and correlates with increased TERT mRNA expression and poorer patient outcome. Promoter methylation, however, is not mutually exclusive to TERT activating genetic alterations, as predicted for functionally redundant mechanisms. To annotate the altered patterns of TERT promoter methylation and their relationship with gene expression, we applied a Pacific Biosciences-based, long-read, bisulfite-sequencing technology and compared the differences in the methylation marks between wild-type and mutant cancers in an allele-specific manner. Results: We cataloged TERT genetic alterations (i.e., promoter point mutations or structural variations), allele-specific promoter methylation patterns, and allele-specific expression levels in a cohort of 54 cancer cell lines. In heterozygous mutant cell lines, the mutant alleles were significantly less methylated than their silent, mutation-free alleles (p < 0.05). In wild-type cell lines, by contrast, both epialleles were equally methylated to high levels at the TERT distal promoter, but differentially methylated in the proximal regions. ChIP analysis showed that epialleles with the hypomethylated proximal and core promoter were enriched in the active histone mark H3K4me2/3, whereas epialleles that were methylated in those regions were enriched in the repressive histone mark H3K27me3. Decitabine therapy induced biallelic expression in the wild-type cancer cells, whereas the mutant cell lines were unaffected. Conclusions: Long-read bisulfite sequencing analysis revealed differences in the methylation profiles and responses to demethylating agents between TERT wild-type and genetically altered cancer cell lines. The causal relation between TERT promoter methylation and gene expression remains to be established

Clinical Significance and Different Expression of Dipeptidyl Peptidase IV and Procalcitonin in Mild and Severe COVID-19

Background: Coronavirus has become a global concern in 2019-20. The virus belongs to the coronavirus family, which has been able to infect many patients and victims around the world. The virus originated in the Chinese city of Wuhan, which eventually spread around the world and became a pandemic. Materials and Methods: A total of 60 Patients with severe (n=30) and mild (n=30) symptoms of COIVD-19 were included in this study. Peripheral blood samples were collected from the patients. Real-time PCR was used to compare the relative expression levels of Procalcitonin and dipeptidyl peptidase IV (DPPIV) in a patient with severe and mild Covid-19 infection. Results: Procalcitonin and dipeptidyl peptidase IV markers in the peripheral blood of patients with severe symptoms, were positive in 29 (96.60%) and 26 (86.60%), respectively (n=30); however, positive rates in the mild symptoms patients group were 27 (90%) and 25 (83.30%), respectively. There was a statistically significant difference between these two groups in terms of DDPIV and Procalcitonin (p&lt;0.001). Conclusion: Procalcitonin and DPPIV increase in patients with COVID-19 infection, significantly higher in the patients with more severe clinical symptoms than those with milder ones. More studies will be needed to verify the reliability of the current findings. Keywords: Procalcitonin, DPPIV, Severe symptoms, Mild symptoms, COVID-1

A novel retinoblastoma therapy from genomic and epigenetic analyses.

Retinoblastoma is an aggressive childhood cancer of the developing retina that is initiated by the biallelic loss of RB1. Tumours progress very quickly following RB1 inactivation but the underlying mechanism is not known. Here we show that the retinoblastoma genome is stable, but that multiple cancer pathways can be epigenetically deregulated. To identify the mutations that cooperate with RB1 loss, we performed whole-genome sequencing of retinoblastomas. The overall mutational rate was very low; RB1 was the only known cancer gene mutated. We then evaluated the role of RB1 in genome stability and considered non-genetic mechanisms of cancer pathway deregulation. For example, the proto-oncogene SYK is upregulated in retinoblastoma and is required for tumour cell survival. Targeting SYK with a small-molecule inhibitor induced retinoblastoma tumour cell death in vitro and in vivo. Thus, retinoblastomas may develop quickly as a result of the epigenetic deregulation of key cancer pathways as a direct or indirect result of RB1 loss

MiT family translocation renal cell carcinomas: A 15th anniversary update.

Microphthalmia (MiT) family translocation renal cell carcinomas (RCCs) are a heterogeneous category of renal tumors which all express MiT transcription factors, typically from chromosomal translocation and rarely from gene amplification. This tumor family has two major subtypes [i.e., Xp11 translocation RCC and t(6;11) RCC] and several related neoplasms (i.e., TFEB amplification RCC and melanotic Xp11 translocation renal cancers). Increased understanding of the clinical, pathological, molecular and prognostic heterogeneity of these tumors, since their official recognition in 2004, provides the opportunity to identify prognostic biomarkers and to understand the reasons for tumor aggression. We will review the literature from the past 15 years and highlight the need for a greater understanding of the molecular mechanisms underpinning heterogeneous tumor behavio

TERT promoter mutations are predictive of aggressive clinical behavior in patients with spitzoid melanocytic neoplasms

Spitzoid neoplasms constitute a morphologically distinct category of melanocytic tumors, encompassing Spitz nevus (benign), atypical Spitz tumor (intermediate malignant potential), and spitzoid melanoma (fully malignant). Currently, no reliable histopathological criteria or molecular marker is known to distinguish borderline from overtly malignant neoplasms. Because TERT promoter (TERT-p) mutations are common in inherently aggressive cutaneous conventional melanoma, we sought to evaluate their prognostic significance in spitzoid neoplasms. We analyzed tumors labeled as atypical Spitz tumor or spitzoid melanoma from 56 patients with available follow-up data for the association of TERT-p mutations, biallelic CDKN2A deletion, biallelic PTEN deletion, kinase fusions, BRAF/NRAS mutations, nodal status, and histopathological parameters with risk of hematogenous metastasis. Four patients died of disseminated disease and 52 patients were alive and disease free without extranodal metastasis (median follow-up, 32.5 months). We found TERT-p mutations in samples from the 4 patients who developed hematogenous metastasis but in none of tumors from patients who had favorable outcomes. Presence of TERT-p mutations was the most significant predictor of haematogenous dissemination (P < 0.0001) among variables analyzed. We conclude that TERT-p mutations identify a clinically high-risk subset of patients with spitzoid tumors. Application of TERT-p mutational assays for risk stratification in the clinic requires large-scale validation