Association between TMPRSS2 rs2070788 polymorphism and COVID-19 severity: a case-control study in multiple cities of Iran.

Introduction: Host genetic variations have been identified as potential influencers of COVID-19 infection. This study aimed to examine the association between transmembrane serine protease type 2 (TMPRSS2) rs2070788 single nucleotide polymorphism (SNP) and the prognosis of COVID-19 in Iranian populations. Method: This case-control study was performed on 756 COVID-19 patients and 59 healthy individuals across Iran. Clinical data, blood samples, and the presence of the TMPRSS2 rs2070788: G>A SNP were determined using T-ARMS-PCR. Additionally, serum levels of tumor necrosis factor α (TNF-α), C-reactive protein (CRP), interleukin-6 (IL-6), and IL-1ß were evaluated in the collected blood samples. Results: No significant association was found between the genotypes and allele frequencies of TMPRSS2 rs2070788 SNP and susceptibility to or mortality from COVID-19 infection. However, we observed a substantial increase in IL-6 and CRP levels associated with the severity of COVID-19, while no such trend was observed for IL-1ß and TNF-α. This study showed a considerable rise in TNF-α and IL-1ß serum levels exclusively in COVID-19 patients with TT rs2070788 TMPRSS2 SNP genotype compared to healthy controls. Conclusion: In this study conducted across multiple cities in Iran, no significant association was found between the TMPRSS2 rs2070788 SNP genotypes and COVID-19 severity or mortality.

An insight into the potential role of LINC00968 in luminal breast cancer: Case-control study and bioinformatics analysis.

Background: Luminal A and B subtypes of breast cancer (BC) comprises up to 70% of all BC patients. LncRNAs can affect many biological and pathological processes, and dysregulation of them is related to human cancers. The potential role of lncRNA LINC00968 in luminal BC is still unclear. Materials and methods: We analyzed the LINC00968 expression across 44 paired luminal BC tissues from the TCGA-BRCA RNA sequencing dataset. Besides, we used the GEPIA2 web server and GENEVESTIGATOR software, as well. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) assay was performed to confirm the LINC00968 expression in 71 paired luminal BC tissues and two luminal A cell lines (MCF7 and T47D). Moreover, to better understanding the potential role of LINC00968 in luminal BC, computational data analyses including co-expression analysis, functional annotation analysis, and genetic alteration analysis have been done. Results: The results of data analyses retrieved from BRCA dataset and databases revealed the significant downregulation of LINC00968 in luminal A and B BC. Also, the results of qRT-PCR in luminal BC tissues and cell lines confirmed the earlier data. LINC00968 expression was negatively associated with tumor stage and lymph node metastasis. Additionally, functional annotation analyses revealed that LINC00968 might be involved in vascular development and angiogenesis, extracellular matrix organization, and cell motility and migration. LINC00968 might play role in some cancer-related signaling pathways. Conclusion: Our study found that downregulation of LINC00968 might promote tumorigenesis, invasion, and metastasis of luminal BC.

Insilco prediction of the role of the FriZZled5 gene in colorectal cancer.

INTRODUCTION: In this study, we aimed to elucidate the crosstalk between the Wnt/ß-catenin signaling pathway and colorectal cancer (CRC) associated with inflammatory bowel disease (IBD) using a bioinformatics analysis of putative common biomarkers and a systems biology approach. MATERIALS AND METHODS: The following criteria were used to search the GEO and ArrayExpress databases for terms related to CRC and IBD: 1. The dataset containing the transcriptomic data, and 2. Untreated samples by medications or drugs. A total of 42 datasets were selected for additional analysis. The GEO2R identified the differentially expressed genes. The genes involved in the Wnt signaling pathway were extracted from the KEGG database. Enrichment analysis and miRNA target prediction were conducted through the ToppGene online tool. RESULTS: In CRC datasets, there were 1168 up- and 998 down-regulated probes, whereas, in IBD datasets, there were 256 up- and 200 down-regulated probes. There were 65 upregulated and 57 downregulated genes shared by CRC and IBD. According to KEGG, there were 166 genes in the Wnt pathway. FriZZled5 (FZD5) was a down-regulated gene in both CRC and IBD, as determined by the intersection of CRC- and IBD-related DEGs with the Wnt pathway. It was also demonstrated that miR-191, miR-885-5p, miR-378a-3p, and miR-396-3p affect the FriZZled5 gene expression. CONCLUSION: It is possible that increased expression of miR-191 and miR-885-5p, or decreased expression of miR-378a -3p and miR396-3, in IBD and CRC results in decreased expression of the FZD5 gene. Based on the function of this gene, FZD5 may be a potential therapeutic target in IBD that progresses to CRC.

The relationship between pregnancy count and duration of breast-feeding with metabolic syndrome (Fasa Persian cohort study).

BACKGROUND: Changes that occur during pregnancy and after that during breastfeeding induce some symptoms similar to metabolic syndrome (MetS) risk factors. This study aims to determine the relationship between pregnancy, as well as the duration of breastfeeding and MetS controlling the effect of other risk factors like hypertension, glucose intolerance, triglyceride, central obesity, and reduction of high-density lipoprotein in women of Fasa Persian Cohort Study. MATERIALS AND METHODS: In this cross-sectional study, 5015 women aged 35-70 years were investigated in the Sheshdeh region from 2016 to 2021, and the information related to the disease symptoms was collected through questionnaires, examinations, and laboratory tests. MetS was calculated based on two guidelines according to adult treatment panel III (ATP III) and international diabetes federation (IDF) methods. For reporting the data, the odds ratio with its 95% confidence interval was used. In order to eliminate the effect of confounders, logistic regression was used. RESULTS: Prevalence of MetS showed a descending trend in women with up to two pregnancies and it reached 22.6% and 22.4% using ATPIII and IDF methods respectively, while with an increase in the number of pregnancies of more than two, MetS prevalence was ascending. The prevalence of MetS did not have any specific trend across various breastfeeding duration groups. Multivariate analysis approved that the odds ratio of developing MetS in comparison with women who had two pregnancies was significantly increasing trend when the pregnancy counts increased. CONCLUSION: The chance of developing MetS based on both IDF and ATP III methods after adjustment for confounding effects would grow with an increase in the number of pregnancies to more than two and breast-feeding of more than seven years. It is recommended that women with more than two pregnancies or the long duration of breast-feeding women undergo a specialized examination to investigate and control MetS problems so that future diseases could be prevented.

Rewiring of miRNA-mRNA bipartite co-expression network as a novel way to understand the prostate cancer related players.

The differential expression and direct targeting of mRNA by miRNA are two main logics of the traditional approach to constructing the miRNA-mRNA network. This approach, could be led to the loss of considerable information and some challenges of direct targeting. To avoid these problems, we analyzed the rewiring network and constructed two miRNA-mRNA expression bipartite networks for both normal and primary prostate cancer tissue obtained from PRAD-TCGA. We then calculated beta-coefficient of the regression-model when miR was dependent and mRNA independent for each miR and mRNA and separately in both networks. We defined the rewired edges as a significant change in the regression coefficient between normal and cancer states. The rewired nodes through multinomial distribution were defined and network from rewired edges and nodes was analyzed and enriched. Of the 306 rewired edges, 112(37%) were new, 123(40%) were lost, 44(14%) were strengthened, and 27(9%) weakened connections were discovered. The highest centrality of 106 rewired mRNAs belonged to PGM5, BOD1L1, C1S, SEPG, TMEFF2, and CSNK2A1. The highest centrality of 68 rewired miRs belonged to miR-181d, miR-4677, miR-4662a, miR-9.3, and miR-1301. SMAD and beta-catenin binding were enriched as molecular functions. The regulation was a frequently repeated concept in the biological process. Our rewiring analysis highlighted the impact of ß-catenin and SMAD signaling as also some transcript factors like TGFB1I1 in prostate cancer progression. Altogether, we developed a miRNA-mRNA co-expression bipartite network to identify the hidden aspects of the prostate cancer mechanism, which traditional analysis -like differential expression- was not detect it.

Female high school students' knowledge and attitude toward breast cancer.

BACKGROUND: Breast cancer is the most common cancer among women. Even though early detection and diagnosis of this disease can reduce mortality considerably, several studies have shown that more than 92% of women are unaware of the risk factors for breast cancer and of breast cancer screening tests. The simultaneous promotion of screening and provision of education can increase community health and reduce medical costs, and students can play a leading role in informing and educating people in society. AIM: The present study aims to examine the level of knowledge and attitude of female students in senior high schools in Fasa regarding breast cancer screening. METHODS: In this cross-sectional study, the random sampling method was applied to survey 350 female high school students, only 311 of whom completed the study. Questionnaires were completed in girls' high schools, and the data was analyzed by SPSS Software, Version 25. RESULTS: The results revealed that more than 87% of students were unaware or had incorrect information regarding breast cancer screening. The link between the type of breast cancer information sources and students' general knowledge was significant. Most students were aware of the risk of breast cancer, but they were uninformed of its symptoms, risk factors, and prevention strategies, and students with a family history of breast cancer had a higher score in terms of mammography knowledge than students with no family history of breast cancer, although this difference was not significant (mean ± standard deviation = 0.94 ± 0.90 vs. 0.67 ± 0.81, p = 0.19). CONCLUSION: The level of awareness and attitude of Fasa high school girls regarding breast cancer and screening methods is not acceptable. Therefore, it is recommended that educational programs be implemented to increase the awareness of students in schools, so that the number of screenings increases with the institutionalization of this information. Likewise, by transferring information through students to their families, the level of awareness in the whole society will hopefully increase as well.

Expression analysis of hsa_circ_0020397, hsa_circ_0005986, hsa_circ_0003028, and hsa_circ_0006990 in renal cell carcinoma.

Renal cell carcinoma (RCC) is a prevalent heterogeneous kidney cancer. So far, different genes have been reported for RCC development. However, its particular molecular mechanism remains unclear. Circular RNAs (circRNAs), a class of non-coding RNAs, are involved in numerous biological processes in different malignancies such as RCC. This study aims to assess the expression and underlying mechanism of four circRNAs (hsa_circ_0020397, hsa_circ_0005986, hsa_circ_0003028, hsa_circ_0006990) with possible new roles in RCC. In the experimental step, we investigated the expression of these four circRNAs in our RCC samples using quantitative real-time polymerase chain reaction. In the bioinformatics step, the differential expressed mRNAs (DEmRNAs), and miRNAs (DEmiRNAs) were obtained from the GEO datasets using the GEO2R tool. A protein-protein interaction network was constructed using the STRING database, and hub genes were identified by Cytoscape. Molecular pathways associated with hub genes were detected using KEGG pathway enrichment analysis. Then, we utilized the ToppGene database to detect the relationships between DEmiRNAs and hub genes. Furthermore, interactions between circRNAs and DEmiRNAs were predicted by the StarBase and circinteractome databases. Finally, a circRNA-DEmiRNA-hub gene triple network was constructed. Our results revealed that the expression of hsa_circ_0020397, hsa_circ_0005986, and hsa_circ_0006990 was downregulated in RCC tissues. Moreover, these circRNAs had a significantly lower expression in patients with a history of kidney disease. Furthermore, hsa_circ_0003028 and hsa_circ_0006990 showed higher expression in the tumor of participants with Lymphovascular/perineural invasion and oncocytoma type, respectively. Based on bioinformatic results, 15 circRNA-DEmiRNA-hub gene ceRNA regulatory axes were predicted, which included three hub genes, five miRNAs, and four selected circRNAs. In conclusion, the current work is the first to emphasize the expression of the hsa_circ_0020397, hsa_circ_0005986, hsa_circ_0003028, and hsa_circ_0006990 in RCC patients presents a novel perspective on the molecular processes underlying the pathogenic mechanisms of RCC.

Air pollution exposure and mammographic breast density in Tehran, Iran: a cross-sectional study.

BACKGROUND: Air pollution is one of the major public health challenges in many parts of the world possibly has an association with breast cancer. However, the mechanism is still unclear. This study aimed to find an association between exposure to six criteria ambient air pollutants (PM2.5, PM10, SO2, NO2, O3, and CO) and mammographic breast density (MBD), as one of the strongest predictors for developing breast cancer, in women living in Tehran, Iran. METHODS: Participants were selected from women attending two university hospitals for screening mammography from 2019 to 2021. Breast density was rated by two expert radiologists. Individual exposures to 3-year ambient air pollution levels at the residence were estimated. RESULTS: The final analysis in 791 eligible women showed that low and high breast density was detected in 34.8 and 62.2 of participants, respectively. Logistic regression analysis after considering all possible confounding factors represented that an increase in each unit of NO2 (ppb) exposure was associated with an increased risk of breast density with an OR equal to 1.04 (95CI: 1.01 to 1.07). Furthermore, CO level was associated with a decreasing breast density (OR = 0.40, 95CI = 0.19 to 0.86). None of the other pollutants were associated with breast density. CONCLUSION: Higher MBD was associated with an increased level of NO2, as a marker of traffic-related air pollution. Furthermore, CO concentration was associated with a lower MBD, while other criteria air pollutants were not related to MBD. Further studies are needed to evaluate the association between ambient air pollutants with MBD.

Potential roles of hsa_circ_000839 and hsa_circ_0005986 in breast cancer.

BACKGROUND: Breast cancer (BC) is one of the leading causes of death among women around the world. Circular RNAs (circRNAs) are a newly discovered group of non-coding RNAs that their roles are being investigated in BC and other cancer types. In this study, we evaluated the association of hsa_circ_0005986 and hsa_circ_000839 in tumor and adjacent normal tissues of BC patients with their clinicopathological characteristics. MATERIALS AND METHODS: Total RNA was extracted from tumors and adjacent non-tumor tissues by the Trizol isolation reagent, and cDNA was synthesized using First Strand cDNA Synthesis Kit (Thermo Scientific). The expression level of hsa_circ_0005986 and hsa_circ_000839 was quantified using RT-qPCR. Online in silico tools were used for identifying potentially important competing endogenous RNA (ceRNA) networks of these two circRNAs. RESULTS: The expression level of hsa_circ_0005986 and hsa_circ_000839 was lower in the tumor as compared to adjacent tissues. The expression level of hsa_circ_0005986 in the patients who had used hair dye in the last 5 years was significantly lower. Moreover, a statistically significant negative correlation between body mass index (BMI) and hsa_circ_000839 expression was observed. In silico analysis of the ceRNA network of these circRNAs revealed mRNAs and miRNAs with crucial roles in BC. CONCLUSION: Downregulation of hsa_circ_000839 and hsa_circ_0005986 in BC tumors suggests a tumor-suppressive role for these circRNAs in BC, meriting the need for more experimentations to delineate the exact mechanism of their involvement in BC pathogenesis.

Altered Expression of hsa_circ_0001445 and hsa_circ_0020397 in Breast Cancer Representing Associations with BMI and Reproductive Factors.

BACKGROUND: Circular RNAs (circRNAs), one of the recent subclasses of non-coding RNAs (ncRNAs), show pivotal functions in regulation of gene expression and have significant roles in malignancies including breast cancer (BC). This study was aimed to assess the hsa_circ_0001445 and hsa_circ_0020397 expression and role in BC, as well as the potential circRNA/miRNA/mRNA crosstalk in these contexts. METHODS: The expression of hsa_circ_0001445 and hsa_circ_0020397 in 50 breast tumors and 50 normal tissues adjacent to the tumors was investigated using quantitative real-time polymerase chain reaction (qRT-PCR). Finally, bioinformatics analyses were used to uncover hsa_circ_0001445, hsa_circ_0020397-miRNA-mRNA potential regulatory networks. RESULTS: The hsa_circ_0001445 expression was considerably downregulated in malignant tissues compared to their normal counterparts (P=0.020), while the hsa_circ_0020397 showed an upregulated pattern (P<0.001). Additionally, it was observed that the higher expression of hsa_circ_0001445 was associated with hair dye avoidance (P=0.034) and normal body mass index (BMI) (P=0.016) while hsa_circ_0020397 over-expression had an important association with a lack of vitamin D consumption (P=0.039). On the other hand, lower expression of hsa_circ_0001445 was significantly associated with age at menarche ˂14 years (P=0.027). Our study also revealed that the two circRNAs have potential ability to regulate key mRNAs and miRNAs in competing endogenous RNA (ceRNA) networks. CONCLUSION: It is suggested that hsa_circ_0001445 and hsa_circ_0020397 with two opposite roles may be involved in BC development through sponging some miRNAs regulating ceRNA networks. However, their molecular interactions should be validated by further functional studies.

The first report of clonidine in vivo/in vitro effects on infertile women with polycystic ovary syndrome (in vivo/in vitro study).

The sympathetic nervous system (SNS) is hyperactive in women with polycystic ovary syndrome (PCOS). This study was designed in two sections: in vivo/in vitro with clonidine as the alpha-2 adrenoceptor (ADR-α2) agonist for modulating this hyperactivity. Eighty women with PCO participated in this randomised clinical trial (in vivo). A clonidine (0.1 mg) tablet was given twice a day for two months. Polycystic ovary morphology (PCOM) and pregnancy rate were the main outcome measurements. In the candidates for in vitro fertilisation (IVF), clonidine was added to the culture medium during IVF for two study groups (PCO-clonidine/PCO-without) and two control groups (egg donors-clonidine/egg donors-without). Our results showed that the pregnancy rate significantly was higher in the study group (p = .002). The mRNA expression of ADR-α1 and ADR-ß2 in PCO was higher than control group (p value <.001). But ADR-α1 expression in PCO-clonidine group decreased (p value = .042), the same as ADR-α2 expression. The intensity of this effect showed a pattern for ADR-α1

Expression profiles and functional prediction of long non-coding RNAs LINC01133, ZEB1-AS1 and ABHD11-AS1 in the luminal subtype of breast cancer.

BACKGROUND: Luminal breast cancer (BC) is the most frequent subtype accounting for more than 70% of BC. LncRNAs, a class of non-coding RNAs with more than 200 nucleotides, are involved in a variety of cellular processes and biological functions. Abberant expression is related to the development of various cancers, such as breast cancer. LINC01133, ZEB1-AS1, and ABHD11-AS1 were reported to be dysregulated in different cancers. However, their expression level in luminal BC remains poorly known. The aim of the present study was to evaluate the potential roles of these lncRNAs in BC, especially in luminal subtypes. METHODS: A comprehensive analysis was performed using the Lnc2Cancer database to identify novel cancer-associated lncRNA candidates. After conducting a literature review, three novel lncRNAs named LINC01133, ZEB1-AS1, and ABHD11-AS1 were chosen as target genes of the present study. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to evaluate the expression level of the mentioned lncRNAs in both luminal BC tissues and cell lines. Then, the correlation of the three mentioned lncRNAs expression with clinicopathological characteristics of the patients was studied. Moreover, several datasets were used to discover the potential roles and functions of LINC01133, ZEB1-AS1 and ABHD11-AS1 in luminal subtype of BC. RESULTS: According to the qRT-PCR assay, the expression levels of LINC01133 and ZEB1-AS1 were decreased in luminal BC tissues and cell lines. On the other hand, ABHD11-AS1 was upregulated in the above-mentioned samples. The expression levels of LINC01133, ZEB1-AS1, and ABHD11-AS1 were not associated with any of the clinical features. Also, the results obtained from the bioinformatics analyses were consistent with qRT-PCR data. Functional annotation of the co-expressed genes with the target lncRNAs, protein-protein interactions and significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways across luminal BC were also obtained using bioinformatics analysis. CONCLUSIONS: Taken together, our findings disclosed the dysregulation of LINC01133, ZEB1-AS1, and ABHD11-AS1 in luminal BC. It was revealed that LINC01133 and ZEB1-AS1 expression was significantly downregulated in luminal BC tissues and cell lines, while ABHD11-AS1 was upregulated considerably in the mentioned tissues and cell lines. Also, bioinformatics and systems biology analyses have helped to identify the possible role of these lncRNAs in luminal BC. However, further analysis is needed to confirm the current findings.

Lipid profile dysregulation in opium users based on Fasa PERSIAN cohort study results.

One of the main health problems in many societies is the increased opium abuse, which was found to be correlated with many problems like cardiovascular disease. This study aimed to evaluate the correlation of opium use with blood lipoproteins as the risk factor of CVD. This was a cross-sectional study conducted on participants of the first phase of the PERSIAN Cohort study who were aged between 35 and 70 years old. Demographic characteristics; history of smoking, alcohol, and opium consumption; medical history; and medications were asked and the related checklists were filled out. The levels of physical activity and fat intake were also registered. As well, lipoprotein profiles were investigated by blood sampling. The linear and logistic regression was used to analyze the relationship between opium and lipid profile and the statistical significant level was considered as < 0.05. Among 9300 participants with a mean age of 48.06 ± 9.44 years old, 49.6% of them were men. About 24.1% of the participants used opium. In the linear regression models, unlike TG (ß = 2.2, p = 0.36), total cholesterol (ß = - 2.5, p = 0.02), LDL (ß = - 2.0, p = 0.04), and HDL (ß = - 1.0, p = 0.04) were significantly lower in people who used opium compared to the others. In the logistic regression models, abnormal level of LDL (OR = 0.78, p = 0.003) and total cholesterol (OR = 0.82, p = 0.008) were less in people who used opium compared to the others. This study showed that there is a correlation between opium usage and lower levels of total cholesterol and LDL; however, the lower level of HDL in normal range was seen in opium users. Considering the current evidences, most of them showed the increased risks of ischemic heart disease, heart attack, hypertension, cerebrovascular disease, and cancer in opium users. Therefore, Healthcare providers and patients should be noticed about the deleterious effects of opium consumption on various vascular events. In addition, it is necessary for managers and policy makers of the health care system to take the necessary measures to raise the level of awareness and health literacy of the general public about the high-risk side effects of opium use and to take necessary and effective strategies to prevent and reduce its use.

The potential roles of lncRNAs DUXAP8, LINC00963, and FOXD2-AS1 in luminal breast cancer based on expression analysis and bioinformatic approaches.

Numerous studies have demonstrated that lncRNAs participate in regulatory networks of different cancers. Dysregulation of various lncRNAs such as DUXAP8, LINC00963, and FOXD2-AS1 has been reported in the development of various cancers. The aim of this study was investigation of the importance and potential roles of DUXAP8, LINC00963, and FOXD2-AS1 in ER+ breast cancer (BC). We examined the expression levels of DUXAP8, LINC00963, and FOXD2-AS1 in 71 luminal A and B tumor tissues and two luminal A cell lines (MCF7 and T47D) compared with adjacent non-tumor tissues and MCF10A cell line by qRT-PCR assay, respectively. For identifying the relation between three lncRNAs and luminal BC, bioinformatic analyses were performed using some databases and software including GENEVESTIGATOR software, GEPIA2, DAVID, REVIGO, STRING, lncATLAS, Kaplan-Meier plotter, starBase, and miRNet tool. The results showed the significant upregulation of all three lncRNAs in luminal A and B tumor specimens and cell lines. Upregulation of DUXAP8 and FOXD2-AS1 was significantly associated with progesterone receptor-positive (PR+) and p53 protein expression in luminal BC patients, respectively. Based on bioinformatic analyses, DUXAP8 can be considered as a prognostic biomarker for patients with luminal BC. DUXAP8, LINC00963, and FOXD2-AS1 are involved in several cancer-associated signaling pathways and multiple cancer-related processes. In addition, bioinformatic analyses indicated that LINC00963/hsa-mir-130a-3p/HSPA8 axis might have potential regulatory role in BC. In conclusion, dysregulation of DUXAP8, LINC00963, and FOXD2-AS1 can play roles in the development of luminal BC. They may exert their functions through involvement in some cancer signaling pathways and processes. In addition, they may interact with miRNAs like predicted interaction of LINC00963 with miR-130a-3p.

Synthesis of pH-sensitive hyaluronic acid nanogels loaded with paclitaxel and interferon gamma: Characterization and effect on the A549 lung carcinoma cell line.

Lung cancer is one of the deadliest cancers in various populations. Apart from the effects that anticancer drugs such as paclitaxel (PTX) have on cancer cells, they also have many side effects on healthy cells. Interferon gamma (IFN-γ) is also one of the cytokines used in the treatment of cancer. Current research is focused on providing new drug carriers to find new therapeutic goals. After synthesis of nanogels and loading of PTX and IFN-γ, the cytotoxicity of these nanogels on A549 and HEK293 healthy cell line was measured by MTT assay and flow cytometry analysis. Finally, the expression of STAT1 gene was investigated using Real time-PCR. The results of MTT assay showed that the survival rate of healthy cells treated with PTX and IFN-γ-loaded nanogels was 2.15 and 2.39 times higher than cancer cells, respectively. The results also showed that the gene expression STAT1 in A549 cells exposed to these nanogels was higher than healthy cells (p < 0.05). Based on flow cytometry results, the death rate of healthy cells treated with the mentioned nanogels was lower than cancer cells (p < 0.05). Therefore, Studies showed that synthesized nanogels have positive effects on cancer cells and also have fewer side effects on healthy cells.

Anti-cancer & anti-metastasis properties of bioorganic-capped silver nanoparticles fabricated from Juniperus chinensis extract against lung cancer cells.

The current study evaluated the anti-cancer properties of bio-functionalized silver nanoparticles fabricated by Juniperus chinensis leaf extracts. The nanoparticles were characterized by scanning electron microscopy, transmission electron microscopy, UV-visible spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, dynamic light scattering, Zeta potential and X-ray spectroscopy. Further, this study elucidated the cellular and molecular mechanisms of nanoparticles for anti-proliferative and apoptotic effects on human lung cancer cells (A549) and compared them with commercial drug cisplatin. The size of the spherical nanoparticle was 12.96 nm with negative zeta potential. Up-regulation of caspase 3,9 and p53, Annexin V-FITC/PI, DAPI staining, and ROS production indicated the remarkable apoptotic effect of AgNPs compared to cisplatin. Moreover, down-regulation of MMP2/MMP9 scratch and matrigel assays revealed anti-metastatic properties of AgNPs. Cell cycle analysis and downregulation of cyclin D1 indicated cancer cell cessation in the G0/G1 phase. Overall, the results revealed that the green-synthetized AgNPs had anti-metastasis and anti-proliferation effects on lung cancer cells in comparison to cisplatin with lower side effects on the normal cell line.

A methylation signature at the CpG island promoter of estrogen receptor beta (ER-ß) in breasts of women may be an early footmark of lack of breastfeeding and nulliparity.

Although little is known regarding the mechanisms behind the onset of breast cancer (BC) through reproductive risk factors, new researches have highlighted some early tumor-related methylation footmarks in the breast tissue of apparently clinically healthy women as their potential epigenetic mechanism. Previous evidence supports that the estrogen receptor beta (ER-ß), whose anti-cancer roles had already been revealed in BC, is downregulated in the breasts of healthy nulliparous women. Nevertheless, data on such a link about its methylation alterations have not been reported. The goal of current study was to determine possible methylation alterations at CpG island promoter of the ER-ß gene, including promoter 0 N and exon 0 N, in relation to aspects of reproductive history in the healthy breasts. The DNA was extracted from the breasts of 120 subjects undergoing cosmetic mammoplasty. Thereafter, the methylation levels of targeted regions in ER-ß gene were determined by using MeDIP-qPCR assay. The results revealed that ER-ß exon 0 N had no methylation in 84.2 % of the women, whereas the rest, comprising 2.5 % and 13.3 % of the samples, showed a lower and higher of its methylation, respectively. Interestingly, nulliparous women were found to have an elevated methylation level of the ER-ß exon 0 N than parous women (P = 0.036). Moreover, we observed a high methylation of the ER-ß exon 0 N in the breasts of non-breastfeeding women compared to breastfeeding subgroup (P = 0.048). Likewise, the non-breastfeeding subgroup showed exon 0N high methylation in comparison to women with breastfeeding >24 months (P = 0.023). Finally, although we found that 6.67 % of the samples had a high methylation level at the promoter 0N, no any relationship was found between its methylation and reproductive history. These results may provide key clues to revealing the epigenetic mechanism through which the nulliparity and lack of breastfeeding influencing the risk factor of BC as well as introducing the potential new early prediction and prevention strategies. Although further investigations need to be done in order to gain a better understanding the roles of these epigenetic signatures.

Expression of ADR-α1, 2 and ADR-ß2 in cumulus cell culture of infertile women with polycystic ovary syndrome and poor responder who are a candidate for IVF: the novel strategic role of clonidine in this expression.

OBJECTIVE: Alpha and beta-adrenoceptors (ADR-α1, 2, and ß2) play a regulatory role in the folliculogenesis and steroidogenesis in the ovarian follicles. This study aimed to measure these adrenoceptors mRNA and its protein levels in cumulus cells (CCs) culture of poor ovarian reserve (POR) and polycystic ovarian syndrome (PCOS) infertile women (IVF candidate) and the effect of clonidine treatment at CCs culture. METHODS: This case/control study was conducted in 2017 includes a control (donation oocytes) and two studies (PCO and POR) groups. The ovulation induction drugs were prescribed in all groups. After the oocyte puncture, the follicular fluid was collected and CCs were isolated were cultured. RNA was extracted and cDNA was synthesized and designed the primer for the ADR-α1, 2 and ADR-ß2 gene expression. The protein levels were investigated by Western Blot. RESULTS: The results showed a high level of three adrenergic expressions in PCO women compared to the control group (p-value <.001), which can be reduced by clonidine. POR group showed a significant decrease in the gene expression of ADR-α1 (p-value = .004) and ADR-α2 (p-value = .003) compared to the control group and clonidine treatment had no effect. CONCLUSION: The significant increase of three adrenoceptors gene expression and protein levels in CCs culture indicate to the hyperactivity of the ovarian sympathetic nervous system at the receptor levels in women with PCOS, and clonidine confirmed it by reducing this expression. In POR women, the reduction of ADR-α1, 2 expressions maybe lead to the aging process in the ovary.

Investigating the prevalence of hypertension and its associated risk factors in a population-based study: Fasa PERSIAN COHORT data.

BACKGROUND: A high prevalence rate of hypertension (HTN) and its subsequent serious complications made this disease a major health-treatment concern in many societies. The current study aimed to investigate the prevalence of hypertension and its associated risk factors in Fasa PERSIAN COHORT in south of Iran in 2019. METHODS: This was an analytical-cross sectional study. The study population were the individuals covered by Fasa cohort. Information of the first phase of Fasa Persian cohort in south of Iran was used in this study. Independent t test, chi-square test, analysis of variances, Pearson correlation coefficient, and multiple stepwise regression were used to analyze the obtained data. Thereafter, the data was analyzed using SPSS software version 22, and P value < 0.05 was considered as statistically significant. RESULTS: Out of 10,111 individuals included in the study, 5546 (54.86%) subjects were women and 4565 (45.16%) other were men. The overall prevalence rate of hypertension was estimated as 46.6%. In the present study, (16/1%) of the participants were with HTN stage 1, and (17/9%) of them were with HTN stage 2. The results show that there were significant positive correlations among HTN and age, BMI, HDL, TG, BUN, ALP, smoking, physical activity, cardiovascular diseases, diabetes, and renal failure (P < 0.5). CONCLUSIONS: Prevalence of HTN in this study population is considerable. Therefore, it is suggested that health system should program some plans to prevent hypertension's prevalence and eliminate its risk factors.

Evaluation of the potential role of long non-coding RNA LINC00961 in luminal breast cancer: a case-control and systems biology study.

BACKGROUND: Luminal subtype is the most common subgroup of breast cancer (BC), accounting for more than 70% of this cancer. Long non-coding RNAs (lncRNAs) are a group of RNAs which play critical roles in diverse cellular processes. It is proved that dysregulation of them can contribute to the development of various cancers, including BC. LINC00961 was reported to be downregulated in several cancers, however, its expression level in BC remains largely unknown. The purpose of the present study was to investigate the possible role of LINC00961 in luminal A and B subtypes of BC. METHODS: To obtain novel lncRNAs associated with different cancers and differentially expressed lncRNAs (DElncRNAs) between BC tumor and normal tissues, Lnc2Cancer and GDC databases were used, respectively. After performing literature review, the expression level of the selected lncRNA (LINC00961) was evaluated in 79 luminal A and B BC specimens and adjacent non-cancerous tissues by Quantitative Reverse Transcription PCR (qRT-PCR). LINC00961 expression was also evaluated in two luminal A BC cell lines, compared to a normal breast cell line. The comparison of the differences between tumor and adjacent non-tumor samples was performed by paired sample t-test. Moreover, correlation analysis between LINC00961 expression and clinicopathological features was performed using the chi-square, fisher exact, and independent t-test. In order to investigate the possible roles of LINC00961 in luminal A and B BC, different bioinformatics analyses such as functional annotation of the LINC00961 co-expressed genes and protein-protein interaction (PPI) networks construction were also performed. RESULTS: LINC00961 was selected as a significant DElncRNA which had not been studied in BC. According to q-RT PCR assay, LINC00961 was downregulated in luminal BC tissues and cell lines. Its expression was correlated with smoking status and the age of menarche in luminal BC patients. Also, the results of the bioinformatics analysis were consistent with the data obtained from q-RT PCR assay. The final results indicated that LINC00961 might be involved in multiple cancer-associated pathways such as chemokine, Ras and PI3K-Akt signaling pathways, GPCR ligand binding, and signal transduction in luminal subtypes of BC. CDH5, GNG11, GNG8, SELL, S1PR1, CCL19, FYN, ACAN, CD3E, ACVRL1, CAV1, and PPARGC1A were identified as the top hub genes of the PPI networks across luminal subgroup. CONCLUSION: Our findings suggested that LINC00961 was significantly downregulated in luminal A and B subtypes of BC. Moreover, bioinformatics analysis provided a basis for better identification of the potential role of LINC00961 in luminal subtype of BC.