Involvement of N4BP2L1, PLEKHA4, and BEGAIN genes in breast cancer and muscle cell development

Patients with breast cancer show altered expression of genes within the pectoralis major skeletal muscle cells of the breast. Through analyses of The Cancer Genome Atlas (TCGA)-breast cancer (BRCA), we identified three previously uncharacterized putative novel tumor suppressor genes expressed in normal muscle cells, whose expression was downregulated in breast tumors. We found that NEDD4 binding protein 2-like 1 (N4BP2L1), pleckstrin homology domain-containing family A member 4 (PLEKHA4), and brain-enriched guanylate kinase-associated protein (BEGAIN) that are normally highly expressed in breast myoepithelial cells and smooth muscle cells were significantly downregulated in breast tumor tissues of a cohort of 50 patients with this cancer. Our data revealed that the low expression of PLEKHA4 in patients with menopause below 50 years correlated with a higher risk of breast cancer. Moreover, we identified N4BP2L1 and BEGAIN as potential biomarkers of HER2-positive breast cancer. Furthermore, low BEGAIN expression in breast cancer patients with blood fat, heart problems, and diabetes correlated with a higher risk of this cancer. In addition, protein and RNA expression analysis of TCGA-BRCA revealed N4BP2L1 as a promising diagnostic protein biomarker in breast cancer. In addition, the in silico data of scRNA-seq showed high expression of these genes in several cell types of normal breast tissue, including breast myoepithelial cells and smooth muscle cells. Thus, our results suggest their possible tumor-suppressive function in breast cancer and muscle development

LncRNA–miRNA–mRNA Networks of Gastrointestinal Cancers Representing Common and Specific LncRNAs and mRNAs

Gastrointestinal (GI) cancers are responsible for approximately half of cancer-related deaths, highlighting the need for the identification of distinct and common features in their clinicopathological characteristics. Long ncRNA (lncRNAs), which are involved in competitive endogenous RNA (ceRNA) networks with critical roles in biological processes, constitute a substantial number of non-coding RNAs. Therefore, our study aimed to investigate the similarities and differences in the ceRNA networks of The Cancer Genome Atlas (TCGA)-GI cancers. We performed a comprehensive bioinformatics analysis of ceRNA networks for TCGA-GI cancers in terms of the deferential mRNA, lncRNA, and miRNA expression levels, ceRNA networks, overall survival analysis, correlation analysis, pathological cancer stages, and gene set enrichment analysis. Our study revealed several common and distinct mRNAs and lncRNAs with prognostic values in these networks. It was specifically noteworthy that MAGI2-AS3 lncRNA was found to be shared in almost all GI cancers. Moreover, the most common shared mRNAs between GI cancers were MEIS1, PPP1R3C, ADAMTSL3, RIPOR2, and MYLK. For each cancer ceRNA network, we found that the expression level of a number of lncRNAs and mRNAs was specific. Furthermore, our study provided compelling evidence that several genes, most notably KDELC1, can act as novel proto-oncogenes in cancers. This, in turn, can highlight their role as new prognostic and therapeutic targets. Moreover, we found cell cycle and extracellular matrix structural constituent as the top shared KEGG and molecular function, respectively, among GI cancers. Our study revealed several known lncRNAs and known and unknown mRNAs in GI cancers with diagnostic and prognostic value

The Effect of Mesenchymal Stem Cells on the Expression of IDOand Qa2 Molecules in Dendritic Cells

Purpose: Mesenchymal stem cells (MSCs) have been shown to reduce the activity of immunecells, including dendritic cells (DCs). But the exact mechanism of mesenchymal inhibitionof DCs is still unknown. In this study, the effect of mesenchymal cells on the expression ofindoleamine dioxygenase (IDO) and Qa2 molecules in DCs was evaluated.Methods: MSCs and DCs were respectively isolated from the bone marrow and spleen of BALB/cmice. Then DCs were co-cultured with MSCs in the present and absence of lipopolysaccharides(LPS). Then the expression of mRNA and protein of IDO and Qa2 molecules were investigatedin DCs that were treated with MSCs.Results: The expression of IDO and Qa2 mRNA in DCs that were treated with MSCs did notsignificantly differ from the control group. The expression of IDO protein in DCs that were coculturedwith MSCs (in 1:10 and 1:50 ratios) in absence of LPS was increased, although theywere not statistically significant (P values: 0.24 and 0.18, respectively). The expression of Qa2protein in DCs that were co-cultured with MSCs (in 1:10 and 1:50 ratios) in presence of LPS wasincreased, although they were not statistically significant (P-values: 0.09 and 0.33, respectively).Conclusion: Our results denied the possibility that MSCs led to the induction of tolerogenic DCsby increasing the expression of the IDO and Qa2 immunomodulatory molecules

Long non-coding RNAs and JAK/STAT signaling pathway regulation in colorectal cancer development

Colorectal cancer (CRC) is one of the main fatal cancers. Cell signaling such as Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling substantially influences the process of gene expression and cell growth. Long non-coding RNAs (lncRNAs) play regulatory roles in cell signaling, cell proliferation, and cancer fate. Hence, lncRNAs can be considered biomarkers in cancers. The inhibitory or activating effects of different lncRNAs on the JAK/STAT pathway regulate cancer cell proliferation or tumor suppression. Additionally, lncRNAs regulate immune responses which play a role in immunotherapy. Mechanisms of lncRNAs in CRC via JAK/STAT regulation mainly include cell proliferation, invasion, metastasis, apoptosis, adhesion, and control of inflammation. More profound findings are warranted to specifically target the lncRNAs in terms of activation or suppression in hindering CRC cell proliferation. Here, to understand the lncRNA cross-talk in CRC through the JAK/STAT signaling pathway, we collected the related in vitro and in vivo data. Future insights may pave the way for the development of novel diagnostic tools, therapeutic interventions, and personalized treatment strategies for CRC patients

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic

The association between polymorphism XRCC1 (rs25487) and the susceptibility of chemical industry workers to benzene

Background & Objective: Benzene, as a carcinogenic compound, can damage DNA by producing free oxygen radicals. Benzene effects have been reported in the blood system. It seems that XRCC1 gene, as a gene involved in the repair of damaged bases, plays a role in the sensitivity of individuals to benzene. The purpose of this study was to investigate the association between rs25487 polymorphism in XRCC1 gene and the susceptibility of chemical industry workers against benzene. Material & Methods: In this case-control study, 60 cases and 60 controls who were exposed to benzene for 2 consecutive years were examined. People who did not have any changes in blood parameters were selected as the control group and those who have shown lymphocytes outside the normal range were considered as a case group. Blood samples were collected from chemical workers. Gene polymorphism was determined by RFLP-PCR using MSP1enzym. Results: There was no significant difference between allelic frequencies A and G (P >0.05). No significant association was found between XRCC1 polymorphism and benzene susceptibility and lymphocytic abnormalities (OR: 1.43, 95% CI (0.47 - 4.31), P = 0.52). Conclusion: It seems that rs25487 polymorphism in the XRCC1 gene does not play a role in the sensitivity of individuals to benzene. Of course, due to the role of XRCC1 gene in response to DNA damage, other polymorphisms of this gene and polymorphism that are targeted in this study are evaluated at a wider level

Content analysis of peace education as one component of global citizenship education in elementary textbooks

Peace education is now a required component of the national curriculum that must be taught by all schools. Hence, it is necessary that peace education components be included in school curricula. So this paper looked at peace education in content of primary textbooks. In other words, Main purpose of this survey was content analysis of primary school textbooks based on peace education components such as "Sense of solidarity," "sense of responsibility to others," "recognizing diversity," "loving others" "discrimination and denial of ethnic, racial or religious." The method of used in the content analysis is Entropy Shanon method based on quantitative content analysis. Unit of analysis is concepts (such as sentence, question, practice, and images) related to cited components in the elementary textbooks. The results showed that "Sense of solidarity" components have the most frequency and lowest frequency related to rejection of ethnic, racist and religious discriminations component

The Role Of MicoRNA 146-A (Rs2910164) In Otitis Media Patients In AL-Najaf Provenance/Iraq

   The current study aims to shows the relationship between gene polymorphisms (SNP( of miRNA 146-a  of  patients infected with otitis media. This finding included 50 samples collected from healthy subject and 100 samples from a patienst suffering from otitis media who attended Al-Sadr Medical City (ENT Department) in Al-Najaf Governorate during the period from February 2022 to June 2022. The samples had an average age ranging from 5 to 70 years. Genotyping of miRNA 146-a  revealed the presence of three genotypes: GG, CG, and CC, representing (16%, 47%, and 37%) respectively in patients with otitis media, while it was (27%, 18%, and 55%) respectively in healthy subjects. CG was common in patients while GG was more common in healthy subjects. MiRNA as potential biomarker of  patients infected with otitis media